The following information was generated from the Hazardous Substances Data Bank (HSDB), a database of the National

Library of Medicine's TOXNET system (http://toxnet.nlm.nih.gov) on February 29, 2012. Query: Records containing the term 50 32 8 1 NAME: Benzo(a)pyrene HSN: 2554 RN: 50-32-8 HUMAN HEALTH EFFECTS: EVIDENCE FOR CARCINOGENICITY: CLASSIFICATION: B2; probable human carcinogen. BASIS FOR CLASSIFICATION: Human data specifically linking benzo(a)pyrene (BAP) to a carcinogenic effect are lacking. There are, however, multiple animal studies in many species demonstrating BAP to be carcinogenic following administration by numerous routes. BAP has produced positive results in numerous genotoxicity assays. NOTE: At the June, 1992 CRAVE Work Group meeting, a revised risk estimate for benzo(a)pyrene was verified. ... The Carcinogenicity Background Document provides details on the rationale and methods used to derive the carcinogenicity values found in IRIS. ... HUMAN CARCINOGENICITY DATA: Inadequate. ANIMAL CARCINOGENICITY DATA: Sufficient. /Based on former classification system/[U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS) on Benzo(a)pyrene (BaP) (50-32-8) Available from, as of March 15, 2000. http://www.epa.gov/iris/] **PEER REVIEWED** A2; Suspected human carcinogen.[American Conference of Governmental Industrial Hygienists. Threshold Limit Values of Chemical Substances and Biological Exposure Indices, ACGIH, Cincinnati, OH 2009, p. 13] **PEER REVIEWED** There is sufficient evidence in experimental animals for the carcinogenicity of benzo[a]pyrene. Benzo[a]pyrene is carcinogenic to humans (Group 1).[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Industrial Exposures, v 92 (2005). Summary available from, as of November 29, 2009: http://monographs.iarc.fr/ENG/Meetings/index1.php] **PEER REVIEWED** No data are available in humans. Sufficient evidence of carcinogenicity in animals. OVERALL EVALUATION: Group 2A: The agent is probably carcinogenic to humans.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. S7 58 (1987)] **PEER REVIEWED** Benzo(a)pyrene: reasonably anticipated to be a human carcinogen. /Polycyclic Aromatic Hydrocarbons/[DHHS/National Toxicology Program; Eleventh Report on Carcinogens: Benzo(a)pyrene (50-32-8) (January 2005). Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s150pah.pdf] **QC REVIEWED**

HUMAN TOXICITY EXCERPTS: /CASE REPORTS/ Persistent nodule ... diagnosed as squamous epithelioma developed in a man who had been exposed to B(a)P for 3 wk while he was carrying out an experiment in mice.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V3 115 (1973)] **PEER REVIEWED** /EPIDEMIOLOGY STUDIES/ Three case-control studies of colorectal adenoma, a precursor of cancer, showed small to moderate increases in risk with higher estimated intake of benzo[a]pyrene. In contrast, there was no association with intake of benzo[a]pyrene in a case-control study of colon cancer. One case-control study of pancreatic cancer found a moderate increase in risk associated with benzo[a]pyrene intake; no association was found in one study of prostatic cancer and non-Hodgkin lymphoma. The available information is at present too limited to draw definitive conclusions.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Industrial Exposures, v 92 (2005). Summary available from, as of November 29, 2009: http://monographs.iarc.fr/ENG/Meetings/index1.php] **PEER REVIEWED** /EPIDEMIOLOGY STUDIES/ A previously reported case-referent study of 85 cases of bladder cancer among aluminum smelter workers and 255 matched referents revealed an excess risk among workers exposed to coal tar pitch volatiles. For the study reported in the present investigation these data have been augmented by estimates of past workplace exposure to total tar (benzene soluble matter) and to benzo[a]pyrene (BaP). From these new data, exposure-response relationships have been estimated by maximum likelihood. A linear relationship between cumulative exposure and relative risk and a minimum latency period of ten years were assumed ... and found compatible with the data. Under these assumptions, relative risk increased for each year of exposure to benzene-soluble matter at a concentration of 1 mg/cu m by 13%, the 95% confidence interval being 5-31. The corresponding figure for BaP (as ug/cu m X yr) was 2.3%. On the basis of these estimates, 40 yr of exposure to benzene-soluble matter at the current exposure limit of 0.2 mg/cu m would lead to a relative risk of 2.4.[Armstrong BG et al; Scand J Work Environ Health 12 (5): 486-93 (1986)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/3787220?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ The relative contributions of biologic and environmental factors on embryo-fetal development were elucidated in a population of pregnant women who were exposed to varying amounts of active cigarette smoke and women who were not exposed to cigarette smoke. The neonatal weight at birth, placental weight at delivery, duration of pregnancy, and placental xenobiotic (polynuclear aromatic hydrocarbon, PAH) metabolism potential were assessed in this population. The overall metabolic capability in exposed and unexposed placental tissue was measured by in vitro assays using microsomes and a polynuclear aromatic hydrocarbon substrate, benzo[a]pyrene (BaP). Toxicity potential was determined by benzo[a]pyrene-metabolite-DNA adduct generation under the same incubation condition. Cigarette smoke exposure increased the overall polynuclear aromatic hydrocarbon metabolism potential in placental tissues by approximately 200% (nonsmoker 176.2 + or - 33.6, n = 25; smoker 524.5 + or - 75.5, n = 32 pmol/mg protein) whereas polynuclear aromatic hydrocarbon-DNA adduct formation potential did not increase significantly over the basal level (nonsmoker 5002 + or - 830, n = 15; smoker 6172 + or

- 1443, n = 22 fmol benzo[a]pyrene equivalent/umol DNA/mg protein). Exposure to cigarette smoke during pregnancy is deleterious to fetal development as reflected by reduced neonatal weight at birth. In contrast, placental weight reduction is indistinct, but placentae expressed markedly augmented overall xenobiotic (PAH) metabolism capability in response to cigarette smoke exposure during pregnancy, indicating placental metabolism may be an important mediator of adverse effects induced by such xenobiotic exposure.[Sanyal MK et al; Reprod Toxicol 8 (5): 411-8 (1994)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/7841660?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ /Investigators/ examined whether food and water are major sources of benzo[a]pyrene (BaP) exposure in this population. /The authors/ used a dietary questionnaire to assess the daily intake of staple food (rice and bread) and water in 3 groups: 40 /esophageal squamous cell carcinoma/ (ESCC) Golestan cases, 40 healthy subjects from the same area, and 40 healthy subjects from a low-risk area in Southern Iran. /Investigators/ measured, by high-performance liquid chromatography combined with fluorescence detection, the BaP concentration of bread, rice, and water in samples obtained from these 3 groups and calculated the daily intake of BaP. Mean BaP concentration of staple foods and water was similar and within standard levels in both areas, but the daily intake of BaP was higher in controls from the high-risk area than in controls from the low-risk area (91.4 vs. 70.6 ng/day, P < 0.01). In the multivariate regression analysis, having ESCC had no independent effect on BaP, whereas residence in the low-risk area was associated with a significant decrease in total BaP intake. Polycyclic aromatic hydrocarbons might, along with other risk factors, contribute to the high risk of ESCC in Golestan.[Hakami R et al; Nutrition and cancer 60 (2): 216-221 (2008). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/18444153?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ In 895 subjects with squamous cell carcinoma of the head and neck (SCCHN) and 898 cancer-free controls matched by age, sex, and ethnicity, /investigators/ validated our previous finding that mutagen sensitivity as measured by the frequency of chromatid breaks in vitro induced by benzo[a]pyrene diol epoxide (BPDE) is an independent risk factor for SCCHN. Using a previously established concentration of 4 micromol/L BPDE to treat short-term cultured primary lymphocytes for 5 hours, /the authors/ evaluated chromatid breaks in 50 well-spread metaphases for each blood sample. The mean frequency of BPDE-induced chromatid breaks was significantly higher in cases than in controls in non-Hispanic Whites (P = 0.0003) but not in other ethnic groups (P = 0.549 for Hispanic Americans and 0.257 for African Americans). The odds ratio associated with risk of SCCHN for the frequency of chromatid breaks greater than median value of controls was 1.56 (95% confidence interval, 1.27-1.91) in non-Hispanic Whites (767 cases and 763 controls) after adjustment for age, sex, smoking status, and drinking status. When the quartiles of the controls were used as the cutoff values, there was a dose response between the degree of mutagen sensitivity and risk of SCCHN in non-Hispanic Whites (P(trend) = 0.0001). However, none of these associations in non-Hispanic Whites was identified in Hispanic Americans (69 cases and 70 controls) or African Americans (59 cases and 65 controls), possibly because of the small samples of these ethnic groups or ethnic difference in genetic variation ...[Wang, LE et al; Cancer research 68 (11): 4479-4485 (2008). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/18519711?dopt=Abstract"

target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ ... In the present study /investigators/ examined the relationship between prenatal PAH exposure and fetal and child growth and development in Tongliang, China, where a seasonally operated coal-fired power plant was the major pollution source. In a cohort of 150 nonsmoking women and their newborns enrolled between 4 March 2002 and 19 June 2002, BaP-DNA adducts were measured in maternal and umbilical cord blood obtained at delivery. The number of gestational months occurring during the period of power plant operation provided a second, more general measure of exposure to plant emissions, in terms of duration. High PAH-DNA adduct levels (above the median of detectable adduct level) were associated with decreased birth head circumference (p=0.057) and reduced children's weight at 18 months, 24 months, and 30 months of age (p < 0.05), after controlling for potential confounders. In addition, in separate models, longer duration of prenatal exposure was associated with reduced birth length (p=0.033) and reduced children's height at 18 (p=0.001), 24 (p < 0.001), and 30 months of age (p < 0.001). The findings suggest that exposure to elevated levels of PAHs, with the Tongliang power plant being a significant source, is associated with reduced fetal and child growth in this population.[Tang, D et al; Environmental Health Perspectives 114 (8): 1297-1300 (2006). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/16882543?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ /Investigators/ evaluated the benefit to neurobehavioral development from the closure of a coal-fired power plant that was the major local source of ambient PAHs. The research was conducted in Tongliang, Chongqing, China, where a coal-fired power plant operated seasonally before it was shut down in May 2004. Two identical prospective cohort studies enrolled nonsmoking women and their newborns in 2002 (before shutdown) and 2005 (after shutdown). Prenatal PAH exposure was measured by PAH-DNA adducts (benzo[a]pyrene-DNA) in umbilical cord blood. Child development was assessed by the Gesell Developmental Schedules at 2 years of age. Prenatal exposure to other neurotoxicants and potential confounders (including lead, mercury, and environmental tobacco smoke) was measured. We compared the cohorts regarding the association between PAH-DNA adduct levels and neurodevelopmental outcomes. Significant associations previously seen in 2002 between elevated adducts and decreased motor area developmental quotient (DQ) (p = 0.043) and average DQ (p = 0.047) were not observed in the 2005 cohort (p = 0.546 and p = 0.146). However, the direction of the relationship did not change. The findings indicate that neurobehavioral development in Tongliang children benefited by elimination of PAH exposure from the coal-burning plant, consistent with the significant reduction in PAH-DNA adducts in cord blood of children in the 2005 cohort. The results have implications for children's environmental health in China and elsewhere.[Perera F et al; Environmental Health Perspectives 116 (10): 1396-1400 (2008). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/18941584?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ To describe the mortality of Quebec aluminum smelter workers employed before 1951. The mortality of 5,977 men hired at three plants on or before January 1, 1951 was compared with that of Quebec men. Relationships to benzo[a]pyrene, benzene-soluble material, and smoking were examined. Statistically significant causes of death were lung cancer (three plants); bladder cancer; chronic obstructive lung disease (two plants each); cancers of the stomach, digestive system unspecified,

rectum and rectosigmoid, pancreas, and larynx; Alzheimer's disease (one plant); and cerebrovascular disease (one plant). Not significant increases were also observed. Mortality from cancer of the lung and bladder and chronic obstructive pulmonary disease are related to exposure in Soderberg smelters. The cause of increased stomach cancer mortality is unclear.[Gibbs GW et al; Journal of Occupational and Environmental Medicine / American College of Occupational and Environmental Medicine 49 (10): 1105-1123 (2007). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/18000416?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ A 14-year update to a previously published historical cohort study of aluminum reduction plant workers was conducted. All men with three or more years at an aluminum reduction plant in British Columbia (BC), Canada between the years 1954 and 1997 were included; a total of 6,423 workers. A total of 662 men were diagnosed with cancer, representing a 400% increase from the original study. Standardized mortality and incidence ratios were used to compare the cancer mortality and incidence of the cohort to that of the BC population. Poisson regression was used to examine risk by cumulative exposure to coal tar pitch volatiles (CTPV) measured as benzene soluble materials (BSM) and benzo[a]pyrene (BaP). The risk for bladder cancer was related to cumulative exposure to CTPV measured as BSM and BaP (p trends < 0.001), and the risk for stomach cancer was related to exposure measured by BaP (p trend BaP < 0.05). The risks for lung cancer (p trend < 0.001), non-Hodgkin lymphoma (p trend < 0.001), and kidney cancer (p trend < 0.01) also increased with increasing exposure, although the overall rates were similar to that of the general population. Analysis of the joint effect of smoking and CTPV exposure on cancer showed the observed dose-response relationships to be independent of smoking.[Spinelli, JJ et al; Cancer Causes &amp; Control: CCC 17 (7): 939-948 (2007). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/16841261?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ Loss of chromosome 9p21 is one of the most frequent genomic alterations in bladder cancer. Alterations of 9p21 and p16 are also frequently seen in the epithelial cells of chronic smokers. /Investigators/ hypothesize that 9p21 is a molecular target of benzo[a]pyrene diol epoxide (BPDE), the metabolic product of tobacco carcinogen benzo[a]pyrene, and 9p21 BPDE sensitivity is a genetic susceptibility factor for bladder cancer. In this case-control study of 203 bladder cancer cases and 198 matched healthy controls, ... the frequencies of BPDE-induced 9p21 aberrations in cultured peripheral blood lymphocytes /were measured/ using fluorescent in situ hybridization and ... the association between 9p21 BPDE sensitivity and bladder cancer risk /was evaluated/. BPDE-induced chromosome 9p21 aberrations were significantly higher in peripheral blood lymphocytes of bladder cancer cases (20.76 +/- 6.97 per 1,000) than those of controls (16.58 +/- 7.07 per 1,000; P < 0.0001). However, no difference was observed for CEP9, a control centromere locus on chromosome 9. Using the median aberration value in the controls as a cutoff point to dichotomize BPDE sensitivity and after adjustment by age, sex, ethnicity, and smoking status, 9p21 BPDE sensitivity was associated with a significantly increased risk of bladder cancer (odds ratio, 5.29; 95% confidence interval, 3.26-8.59), whereas the odds ratio for the CEP9 locus was 0.99 (95% confidence interval, 0.66-1.50). There was also a dose-response relationship between the 9p21 BPDE sensitivity and increased risk for bladder cancer. 9p21 may be a molecular target for BPDE damage in bladder cancer cases and 9p21 BPDE

sensitivity may be a marker of bladder cancer susceptibility./Benzo[a]pyrene diol epoxide/[Gu, Jian et al; Cancer Epidemiology, Biomarkers &amp; Prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 17 (9): 2445-2450 (2008). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/18768515?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ To describe the cancer experience of Quebec aluminum smelter workers. METHODS: Cancer incidence was compared with that of the Quebec general population and examined in relation to benzo[a]pyrene (B[a]P) and smoking exposure indices. RESULTS: There was a statistically significant increased incidence of stomach (two cohorts), pancreatic (one cohort), laryngeal (one cohort), lung (three cohorts), and bladder (four cohorts) cancers. Unlike lung and bladder cancers, pancreatic and stomach cancer risks do not relate meaningfully to cumulative B[a]P exposure. Laryngeal and buccal cavity cancer standardized incidence ratios (SIRs) seem to increase with increasing B[a]P exposure. SIRs from lung cancer have greatly diminished whereas bladder cancer SIRs remain elevated in all but one cohort. CONCLUSIONS: The cancer incidence results are consistent with those from mortality studies, but identify other cancers that deserve scrutiny in future follow-ups.[Gibbs GW, Sevigny M; Journal of Occupational and Environmental Medicine / American College of Occupational and Environmental Medicine 49 (12): 1351-1366 (2007). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/18231082?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ ...In the present study /investigators/ evaluated the association between prenatal exposure to these pollutants and child development measured by the Gesell Developmental Schedules at 2 years of age. The study was conducted in Tongliang, Chongqing, China, where a seasonally operated coal-fired power plant was the major source of ambient PAHs and also contributed lead and mercury to the air. In a cohort of nonsmoking women and their newborns enrolled between March 2002 and June 2002, /investigators/ measured levels of PAH-DNA adducts, lead, and mercury in umbilical cord blood. PAH-DNA adducts (specifically benzo[a]pyrene adducts) provided a biologically relevant measure of PAH exposure. /The authors/ also obtained developmental quotients (DQs) in motor, adaptive, language, and social areas. Decrements in one or more DQs were significantly associated with cord blood levels of PAH-DNA adducts and lead, but not mercury. Increased adduct levels were associated with decreased motor area DQ (p = 0.043), language area DQ (p = 0.059), and average DQ (p = 0.047) after adjusting for cord lead level, environmental tobacco smoke, sex, gestational age, and maternal education. In the same model, high cord blood lead level was significantly associated with decreased social area DQ (p = 0.009) and average DQ (p = 0.038). The findings indicate that exposure to pollutants from the power plant adversely affected the development of children living in Tongliang...[Tang D et al; Environmental Health Perspectives 116 (5): 674-679 (2008). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/18470301?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ The frequencies of base-line and benzo[a]pyrene (BaP) induced sister chromatid exchanges (SCE) were measured in peripheral blood lymphocytes from 22 male asbestos-exposed workers and 10 nonexposed workers of comparable age. A clear association between cigarette smoking and asbestos exposure in the sensitivity of lymphocytes to BaP was

observed. Among asbestos-exposed workers, lymphocytes from those who smoked cigarettes were significantly more susceptible to the induction of sister chromatid exchanges by in vitro exposure to BaP (p = 0.01) than were lymphocytes from nonsmokers. Active smoking elevated the base-line sister chromatid exchange frequency in both asbestos-exposed and nonexposed workers (p = 0.001), and an interaction between smoking and asbestos in the production of base-line sister chromatid exchange was suggested (p = 0.07). Asbestos exposure alone was not associated with an enhanced susceptibility to the induction of sister chromatid exchanges by BaP or with an elevation of base-line sister chromatid exchange. Increased age was associated with an increase in sister chromatid exchanges inducibility by BP (p = 0.01), and a history of smoking was marginally associated with sister chromatid exchanges inducibility by BaP (p = 0.07). These findings support the hypothesis that an increased susceptibility of asbestos-exposed individuals to polyaromatic hydrocarbon-induced cancer results from an enhanced sensitivity to the induction of genetic damage rather than to an asbestos-induced differential cellular metabolic capacity.[Kelsey KT et al; JNCI 77 (2): 321-7 (1986). Available from, as of November 21, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/3461194?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ Polycyclic aromatic hydrocarbons (PAHs), including benzo[a]pyrene (BaP), are air pollutants released by the World Trade Center (WTC) fires and urban combustion sources. BaP-DNA adducts provide a measure of PAH-specific genetic damage, which has been associated with increased risk of adverse birth outcomes and cancer. /Investigators/ previously reported that levels of BaP-DNA adducts in maternal and umbilical cord blood obtained at delivery were elevated among subjects who had resided within 1 mile of the WTC site during the month after 9/11; and that elevated blood adducts in combination with in utero exposure to environmental tobacco smoke (ETS) were significantly associated with decreased fetal growth. /The authors/ aim was to assess possible effects of prenatal exposure to WTC pollutants on child development. After 11 September 2001, /investigators/ enrolled a cohort of nonsmoking pregnant women who delivered at three lower Manhattan hospitals. We have followed a subset of children through their third birthdays and measured cognitive and motor development using the Bayley-II Scales of Child Development (BSID-II). In multivariate analyses, we found a significant interaction between cord blood adducts and in utero exposure to ETS on mental development index score at 3 years of age (p = 0.02, n = 98) whereas neither adducts nor ETS alone was a significant predictor of (BSID-II) cognitive development. Although limited by small numbers, these results suggest that exposure to elevated levels of PAHs in conjunction with prenatal ETS exposure may have contributed to a modest reduction in cognitive development among cohort children.[Perera FP et al; Environmental Health Perspectives 115(10): 1497-1502 (2007). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/17938742?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ /Investigators/ examined the risk of mortality and cancer incidence with quantitative exposure to benzene-soluble fraction (BSF), benzo(a)pyrene (BaP), fluoride, and inhalable dust in two Australian prebake smelters. A total of 4,316 male smelter workers were linked to mortality and cancer incidence registries and followed from 1983 through 2002 (mean follow-up: 15.9 years, maximum: 20 years). Internal comparisons using Poisson regression were undertaken based on quantitative exposure levels. Smoking-adjusted, monotonic relationships were observed between respiratory cancer and cumulative inhalable dust exposure (trend p

= 0.1), cumulative fluoride exposure (p = 0.1), and cumulative BaP exposure (p = 0.2). The exposure-response trends were stronger when examined across the exposed categories (BaP p = 0.1; inhalable dust p = 0.04). A monotonic, but not statistically significant trend was observed between cumulative BaP exposure and stomach cancer (n = 14). Bladder cancer was not associated with BaP or BSF exposure. No other cancer and no mortality outcomes were associated with these smelter exposures. The carcinogenicity of Soderberg smelter exposures is well established; in these prebake smelters we observed an association between smelter exposures and respiratory cancer, but not bladder cancer. The exploratory finding for stomach cancer needs confirmation. These results are preliminary due to the young cohort and short follow-up time.[Friesen MC et al; Cancer Causes &amp; Control: CCC 20 (6): 905-916 (2009). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/19294522?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ To compare the dose-response relationships for two common measures of coal tar-derived substances, benzene-soluble material (BSM) and benzo[a]pyrene (BaP), and to evaluate which among these is more strongly related to the health outcomes. The study population consisted of 6423 men with > or =3 years of work experience at an aluminium smelter (1954-97). Three health outcomes identified from national mortality and cancer databases were evaluated: incidence of bladder cancer (n = 90), incidence of lung cancer (n = 147) and mortality due to acute myocardial infarction (AMI, n = 184). The shape, magnitude and precision of the dose-response relationships and cumulative exposure levels for BSM and BaP were evaluated. Two model structures were assessed, where 1n(relative risk) increased with cumulative exposure (log-linear model) or with log-transformed cumulative exposure (log-log model). The BaP and BSM cumulative exposure metrics were highly correlated (r = 0.94). The increase in model precision using BaP over BSM was 14% for bladder cancer and 5% for lung cancer; no difference was observed for AMI. The log-linear BaP model provided the best fit for bladder cancer. The log-log dose-response models, where risk of disease plateaus at high exposure levels, were the best-fitting models for lung cancer and AMI. BaP and BSM were both strongly associated with bladder and lung cancer and modestly associated with AMI.[Friesen MC et al; Occupational and Environmental Medicine 64 (4): 273-278 (2007). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/17053015?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ In this large confirmatory study of 803 patients with squamous cell carcinoma of head and neck (SCCHN) and 839 controls frequency matched by age, sex, and ethnicity, we further examined potential predictors of benzo[a]pyrene diol epoxide (BPDE)-induced adduct levels and their associations with SCCHN risk. BPDE-DNA adduct levels were determined by the (32)P-postlabeling method in peripheral lymphocytes after in vitro challenged by BPDE. We also genotyped for GSTM1 null, GSTT1 null, GSTP1 Ile(105)Val, and GSTP1 Ala(114)Val. Potential predictors of BPDE-DNA adducts were evaluated by stratification and multivariate linear regression analyses and the association between adduct levels and SCCHN risk by multivariate logistic regression analyses. We found that mean BPDE-DNA adduct levels (the relative adduct labeling x 10(7) +/- SD) were significantly higher in cases (77.6 +/- 111.8) than in controls (57.3 +/98.3; P < 0.001). Using the median control value (29.22) as a cutoff, 63% of the cases were distributed above this level (adjusted odds ratio, 1.71; 95% confidence interval, 1.39-2.10). A significant dose-response relationship was observed between adduct quartiles and SCCHN risk

(P(trend) < 0.001). Multivariate linear regression analysis revealed that ethnicity and smoking were significant predictors of BPDE-DNA adduct levels in controls. In conclusion, we confirmed the previously reported association between in vitro BPDE-induced DNA adduct levels and SCCHN risk, and the assay may help identify individuals at high risk of developing smoking-related cancers.[Li, D et al; Cancer research 67 (12): 5628-5634 (2007). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/17575128?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ ... Primary lung cancer cases (n = 2,101) were recruited from 13 hospitals within the Lombardy region of Italy examining approximately 80% of the cases from the area. Noncancer population controls (n = 2,120), matched to cases on gender, residence, and age, were randomly selected from the same catchment area. Diet was assessed in 1,903 cases and 2,073 controls and used in conjunction with a meat mutagen database to estimate intake of heterocyclic amines (HCA) and benzo[a]pyrene (BaP). Multivariable odds ratios (OR) and 95% confidence intervals (95% CI) for sex-specific tertiles of intake were calculated using unconditional logistic regression. Red and processed meat were positively associated with lung cancer risk (highest-versus-lowest tertile: OR, 1.8; 95% CI, 1.5-2.2; P trend < 0.001 and OR, 1.7; 95% CI, 1.4-2.1; P trend < 0.001, respectively); the risks were strongest among never smokers (OR, 2.4; 95% CI, 1.4-4.0; P trend = 0.001 and OR, 2.5; 95% CI, 1.5-4.2; P trend = 0.001, respectively). HCAs and BaP were significantly associated with increased risk of lung cancer. When separated by histology, significant positive associations for both meat groups were restricted to adenocarcinoma and squamous cell carcinoma but not small cell carcinoma of the lung. In summary, red meat, processed meat, and meat mutagens were independently associated with increased risk of lung cancer.[Lam TK et al; Cancer Research 69 (3): 932-939 (2009). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/19141639?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ To investigate the association between dietary exposure to food mutagens and risk of pancreatic cancer, /investigators/ conducted a hospital-based case-control study at the University of Texas M. D. Anderson Cancer Center during June 2002 to May 2006. A total of 626 cases and 530 noncancer controls were frequency matched for race, sex and age (+/-5 years). Dietary exposure information was collected via personal interview using a meat preparation questionnaire. A significantly greater portion of the cases than controls showed a preference to well-done pork, bacon, grilled chicken, and pan-fried chicken, but not to hamburger and steak. Cases had a higher daily intake of food mutagens and mutagenicity activity (revertants per gram of daily meat intake) than controls did. The daily intakes of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and benzo[a]pyrene (BaP), as well as the mutagenic activity, were significant predictors for pancreatic cancer (P = 0.008, 0.031, and 0.029, respectively) with adjustment of other confounders. A significant trend of elevated cancer risk with increasing DiMeIQx intake was observed in quintile analysis (P(trend) = 0.024). A higher intake of dietary mutagens (those in the two top quintiles) was associated with a 2-fold increased risk of pancreatic cancer among those without a family history of cancer but not among those with a family history of cancer. A possible synergistic effect of dietary mutagen exposure and smoking was observed among individuals with the highest level of exposure (top 10%) to /2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine/ (PhIP) and BaP, P(interaction) = 0.09 and 0.099, respectively. These data support the

hypothesis that dietary mutagen exposure alone and in interaction with other factors contribute to the development of pancreatic cancer.[Li D et al; Cancer Epidemiology, Biomarkers &amp; Prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 16 (4): 655-661 (2007). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/17416754?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ Panax ginseng C.A. Meyer has been the most highly recognized medicinal herb in the Orient. The prolonged administration of red ginseng extract significantly inhibits the incidence of hepatoma and also proliferation of pulmonary tumors induced by aflatoxin B(1) and urethane. Statistically significant anticarcinogenic effects were in aged or heat treated extracts of ginseng and red ginseng made by steaming in a 9 weeks medium-term anticarcinogenicity test using benzo[a]pyrene. In case-control studies, odds ratios (OR) of the cancer of lip, oral cavity and pharynx, larynx, lung, esophagus, stomach, liver, pancreas, ovary, and colorectum were significantly reduced. As to the type of ginseng, the ORs for cancer were reduced in user of fresh ginseng extract intakers, white ginseng extract, white ginseng powder, and red ginseng. In a cohort study with 5 years follow-up conducted in a ginseng cultivation area, ginseng users had a decreased relative risk (RR) compared with non-users. The relative risks (RRs) of ginseng users were decreased in gastric cancer and lung cancer. These findings strongly suggest that Panax ginseng C.A. Meyer cultivated in Korea has non-organ specific cancer preventive effects against various cancers. To investigate the active components for cancer prevention, several fractions of fresh and red ginseng and four semi-synthetic ginsenoside Rh(1), Rh(2), Rg(3) and Rg(5), the major saponin components in red ginseng, were prepared among the ginsenosides. By using Yun's model, Rg(3) and Rg(5) showed statistically significant reduction of lung tumor incidence and Rh(2) had a tendency to decrease the incidence. In conclusion, these results strongly suggested that Panax ginseng C.A. Meyer cultivated in Korea is a non-organ specific cancer preventive against human cancers and also indicated that the anticarcinogenicity or human cancer preventive effect of Panax ginseng is due to ginsenoside Rg(3), Rg(5) and Rh(2).[Yun TK et al; Mutation research 63 (74): 523-524 (2003). Available from, as of November 24, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/12628504?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ /Investigators/ sought to assess the association between dietary intake of /heterocyclic amines/ (HCA) and benzo[a]pyrene [BaP] and exocrine pancreatic cancer in a population-based case-control study. Subjects (193 cases and 674 controls) provided information on their usual meat intake and preparation method, eg, stewed, fried, or grilled/barbecued, etc. Meat doneness preferences were measured using photographs that showed internal doneness and external brownness. ... A meat-derived HCA, B[a]P, and mutagen database with a questionnaire /were used/ to estimate intake of /amino-1-methyl-6-phenylimidazo[4,5-b]pyridine/ (PhIP), DiMeIQx, MeIQx, BaP, and mutagenic activity (revertants/g of daily meat intake). Data were analyzed with unconditional logistic regression. In analyses adjusted for age, sex, smoking, education, race, and diabetes, the odds ratio and 95% confidence interval for the highest compared with the lowest quintile were as follows: PhIP, 1.8 (1.0-3.1); DiMeIQx, 2.0 (1.2-3.5); MeIQx, 1.5 (0.9-2.7); B(a)P, 2.2 (1.2-4.0); and mutagenic activity, 2.4 (1.3-4.3). HCAs and BaP from well-done barbecued and pan-fried meats may be associated with increased risk for pancreatic cancer.[Anderson KE et al;

Cancer Epidemiology, Biomarkers &amp; Prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 14 (9): 2261-2265 (2005). Available from, as of November 23 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/16172241?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ Carcinogen-DNA adducts, a measure of procarcinogenic genetic damage, are considered a biomarker of increased cancer risk. Here /investigators/ compare the levels of benzo[a]pyrene-DNA adducts as a proxy for PAH-DNA damage measured in maternal blood and newborn cord blood obtained at delivery in four different populations of mothers (total of 867) and newborns (total of 822), representing a 30-fold range of exposure to ambient PAHs. The populations include residents in Northern Manhattan, participants in a study of the effects of the World Trade Center disaster, residents in Krakow, Poland, and residents in Tongliang, China. Mean adduct concentrations in both maternal and cord blood and the proportion of samples with detectable adducts, increased across the populations [Northern Manhattan < World Trade Center (WTC) < Krakow < Tongliang], consistent with the trend in estimated ambient exposure to PAHs (P < 0.001). For mothers, the means in the respective populations were Northern Manhattan (0.21 adducts per 10+8 nucleotides), WTC (0.23 adducts per 10+8 nucleotides), Krakow (0.28 adducts per 10+8 nucleotides), Tongliang (0.31 adducts per 10+8 nucleotides); the corresponding means in the newborns were Northern Manhattan (0.23), WTC (0.24), Krakow (0.29), Tongliang (0.31). The percentage of mothers with detectable levels of adducts in the respective populations were Northern Manhattan (36.8%), WTC (57.5%), Krakow (72.9%), Tongliang (73.4%); the corresponding percentages among the newborns were Northern Manhattan (42.4%), WTC (60.6%), Krakow (71.1%), Tongliang (79.5%). Despite the estimated 10-fold lower PAH dose to the fetus based on laboratory animal experiments, the adduct levels in the newborns were similar to or higher than in the mothers. This study suggests that the fetus may be 10-fold more susceptible to DNA damage than the mother and that in utero exposure to polycyclic aromatic hydrocarbons may disproportionately increase carcinogenic risk. The data support preventive policies to limit PAH exposure to pregnant women and children.[Perera F et al; Cancer Epidemiology, Biomarkers &amp; Prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 14 (3): 709-714 (2005). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/15767354?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ Inner-city minority populations are high-risk groups for adverse birth outcomes and also more likely to be exposed to environmental contaminants, including environmental tobacco smoke (ETS), benzo[a]pyrene B[a]P, other ambient polycyclic aromatic hydrocarbons (global PAHs), and residential pesticides. The Columbia Center for Children's Environmental Health (CCCEH) is conducting a prospective cohort study of 700 northern Manhattan pregnant women and newborns to examine the effects of prenatal exposure to these common toxicants on fetal growth, early neurodevelopment, and respiratory health. ...To evaluate the effects of prenatal exposure to ETS, PAHs, and pesticides, researchers analyzed questionnaire data, cord blood plasma (including biomarkers of ETS and pesticide exposure), and B[a]P-DNA adducts (a molecular dosimeter of PAHs). Self-reported ETS was associated with decreased head circumference (P = 0.04), and there was a significant interaction between ETS and adducts such that combined exposure had a significant multiplicative effect on birth weight (P = 0.04) and head circumference (P = 0.01) after

adjusting for confounders. A second analysis examined the neurotoxic effects of prenatal ETS exposure and postpartum material hardship (unmet basic needs in the areas of food, housing, and clothing) on 2-year cognitive development. Both exposures depressed cognitive development (P < 0.05), and there was a significant interaction such that children with exposure to both ETS and material hardship exhibited the greatest cognitive deficit (7.1 points). A third analysis found that cord chlorpyrifos, and a combined measure of cord chlorpyrifos, diazinon, and propoxur-metabolite, were inversely associated with birth weight and/or length (P < 0.05). These results underscore the importance of policies that reduce exposure to ETS, air pollution, and pesticides with potentially adverse effects on fetal growth and child neurodevelopment.[Perera, FP et al; Neurotoxicology 26 (4): 573-587 (2005). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/16112323?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ /Investigators/ carried out a clinic-based case-control study specifically designed to address the hypothesis that dietary intake of polycyclic aromatic hydrocarbons (PAH) is associated with colorectal adenoma risk.A food frequency questionnaire with detailed questions on meat-cooking methods and doneness levels and a benzo[a]pyrene (BaP) database (as a surrogate for total carcinogenic PAHs) based on the collection and analysis of a wide range of food samples /were used to estimate/ BaP intake derived from meat and from all foods to test its relationship with risk of colorectal adenomas. The median (10th and 90th percentiles) BaP intake in controls was 5 ng/d (0.2 and 66 ng/d) estimated from meat and 73 ng/d (35 and 140 ng/d) from all foods. In cases, median BaP intake was 17 ng/d (0.5 and 101 ng/d) from meat and 76 ng/d (44 and 163 ng/d) from all foods. Multivariate analysis was carried out on 146 cases and 228 controls. The odds ratios (95% confidence interval) for dietary BaP from meat with the first quintile as the reference group were 1.19 (0.51-2.80) for the second quintile, 1.71 (0.76-3.83) for the third quintile, 2.16 (0.96-4.86) for the fourth quintile, and 2.82 (1.24-6.43) for the fifth quintile (Ptrend=0.01). Increased risk of colorectal adenomas was more strongly associated with BaP intake estimated from all foods: 2.61 (1.08-6.29) for the second quintile, 4.21 (1.79-9.91) for the third quintile, 2.45 (0.98-6.12) for the fourth quintile, and 5.60 (2.20-14.20) for the fifth quintile (Ptrend=0.002). This study provides evidence that dietary BaP plays a role in colorectal adenoma etiology.[Sinha R et al; Cancer Epidemiology, Biomarkers &amp; Prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 14 (8): 2030-2034 (2005). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/16103456?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ ... To test the hypothesis that genetically determined apoptotic capacity (AC) is associated with risk of lung cancer, /investigators/ conducted a pilot case-control study of 68 patients with newly diagnosed, untreated lung cancer and 74 cancer-free controls. /The authors/ measured the AC of their cultured peripheral blood lymphocytes in response to in vitro exposure to an ultimate tobacco carcinogen, benzo[a]pyrene diol epoxide (BPDE), by using terminal dUTP nucleotide end labeling and flow cytometry. /The authors/ also investigated the frequency of the -A670G polymorphism in Fas, a gene involved in controlling the apoptotic pathway, by using polymerase chain reaction-restriction fragment length polymorphism analysis. After exposing the cells to 4 uM BPDE for 5 hr, /investigators/ observed a significantly lower AC in lung cancer patients (155.2+/-143.9%) than in the controls (216.6+/-184.6%)

(P < 0.05). Low AC was an independent risk factor (adjusted odds ratio (OR)=2.69, 95% confidence interval (CI)=1.18-6.15) for lung cancer after adjustment for age, sex, ethnicity, smoking status and apoptotic baseline in a logistic regression model. Although the Fas -A670G polymorphism was not an independent risk factor for lung cancer, it appeared to modulate the risk. The adjusted ORs for lung cancer risk associated with lower AC were 4.00 (95% CI=1.48-10.80) among those with the Fas -670 AG and GG genotypes and 0.97 (95% CI=0.18-5.30) among those with the Fas -670AA genotype. These data suggest that alteration in the apoptotic pathway may be a risk factor for lung cancer and this risk may be modulated by the Fas -A670G polymorphism. ...[Wang LE et al; Lung cancer (Amsterdam, Netherlands) 42 (1): 1-8 (2003). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/14512182?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ /The authors/ studied a relation between exposure to PAH and mortality from IHD (418 cases) in a cohort of 12,367 male asphalt workers from Denmark, Finland, France, Germany, Israel, The Netherlands and Norway. The earliest follow up (country-specific) started in 1953 and the latest ended in 2000, averaging 17 years. Exposures to benzo[a]pyrene were assessed quantitatively using measurement-driven exposure models. Exposure to coal tar was assessed in a semiquantitative manner on the basis of information supplied by company representatives /and/ sensitivity analyses /was used/ to assess potential confounding by tobacco smoking. Both cumulative and average exposure indices for benzo[a]pyrene were positively associated with mortality from IHD. The highest relative risk for fatal IHD was observed for average benzo[a]pyrene exposures of 273 ng/m or higher, for which the relative risk was 1.64 (95% confidence interval=1.13-2.38). Similar results were obtained for coal tar exposure. Sensitivity analysis indicated that even in a realistic scenario of confounding by smoking, we would observe approximately 20% to 40% excess risk in IHD in the highest PAH-exposure categories. /These/ results lend support to the hypothesis that occupational PAH exposure causes fatal IHD and demonstrate a consistent exposure-response relation for this association.[Burstyn I et al; Epidemiology (Cambridge, Mass.) 16 (6): 744-750 (2005). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/16222163?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ Reported habits of red meat consumption, particularly red meat that has been cooked to the degree termed 'well-done', is a positive risk factor for colorectal cancer. Under high, pyrolytic temperatures, heterocyclic amines (HCA) and benzo[a]pyrene (BP) molecules can form inside and on the surface of red meat, respectively. These compounds are precursors that are metabolically converted to compounds known to act as mutagens and carcinogens in animal models, yet their role in human colorectal carcinogenesis remains to be clarified. /The authors/ investigated whether intake of these compounds is associated with risk of colorectal adenoma in the context of a polyp-screening study conducted in Southern California. Using a database of individual HCAs and BP in meats of various types and subjected to specified methods and degrees of cooking, ... nanogram consumption of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, 2-amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline and benzo[a]pyrene (BP) /were estimated/. A 6% increased risk of large ( > 1 cm) adenoma per 10 ng/day consumption of BP [OR = 1.06 (95% CI, 1.00-1.12), P (trend) = 0.04] /was observed/. A major source of BP is red meat exposed to a naked flame,

as occurs during the barbecuing process. Consistent with this finding an incremental increase of 10 g of barbecued red meat per day was associated with a 29% increased risk of large adenoma [OR = 1.29 (95% CI, 1.02-1.63), P (trend) = 0.04]. Individuals in the top quintile of barbecued red meat intake were at increased risk of large adenoma [OR = 1.90 (95% CI, 1.04-3.45)], compared with never consuming barbecued red meat. The consumption of oven-broiled red meat was inversely related to adenoma risk compared with non-consumers [OR = 0.49 (95% CI, 0.28-0.85)]. /The authors/ did not identify any association with consumption of individual HCAs and colorectal adenoma risk.[Gunter MJ et al; Carcinogenesis 26 (3): 637-642 (2005). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/15579480?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ ... Meat cooked well-done using high-temperature cooking techniques produces heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) such as benzo[a]pyrene (B[a]P). This study was conducted as a population-based case-control study in Iowa, Detroit, Seattle and Los Angeles and was designed to determine whether meat, meat-cooking methods, HCAs or PAHs from meat were associated with Non-Hodgkin Lymphoma (NHL) risk. This study consisted of 458 NHL cases, diagnosed between 1998 and 2000, and 383 controls. Participants completed a 117-item food frequency questionnaire (FFQ), with graphical aids to assess the meat-cooking method and doneness level, which was linked to a HCA and B[a]P database. Logistic regression, comparing the fourth to the first quartile, found no association between red meat or processed meat intake and risk for NHL [odds ratio (OR) and 95% confidence interval (CI): 1.10 (0.67-1.81) and 1.18 (0.74-1.89), respectively]. A marginally significant elevated risk for NHL was associated with broiled meat [OR and 95% CI: 1.32 (0.99-1.77); P trend = 0.09], comparing those who consumed broiled meat with those who did not. The degree to which meat was cooked was not associated with the risk for NHL, although one of the HCAs, DiMeIQx (2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline), was associated with an inverse risk. Fat intake was associated with a significantly elevated risk for NHL [OR and 95% CI: 1.60 (1.05-2.45); P trend = 0.12]; in contrast, animal protein was inversely associated with risk for NHL [OR and 95% CI: 0.39 (0.22-0.70); P trend = 0.004]. Overall, our study suggests that consumption of meat, whether or not it is well-done, does not increase the risk of NHL. Furthermore, neither HCAs nor B[a]P from meat increase the risk of NHL.[Cross AJ; Carcinogenesis 27 (2): 293-297 (2006). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/16113054?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ Typical polycyclic aromatic hydrocarbon mixtures are established lung carcinogens, but the quantitative exposure-response relationship is less clear. To clarify this relationship... a review and meta-analysis of published reports of occupational epidemiologic studies /were conducted/. Thirty-nine cohorts were included. The average estimated unit relative risk (URR) at 100 ug/cu m) years benzo[a]pyrene was 1.20 [95% confidence interval (CI), 1.11-1.29] and was not sensitive to particular studies or analytic methods. However, the URR varied by industry. The estimated means in coke ovens, gasworks, and aluminum production works were similar (1.15-1.17). Average URRs in other industries were higher but imprecisely estimated, with those for asphalt (17.5; CI, 4.21-72.78) and chimney sweeps (16.2; CI, 1.64-160.7) significantly higher than the three above. There was no statistically significant variation of URRs within industry or in relation to study design (including whether adjusted for smoking), or source of exposure information. Limited information on total dust exposure did not suggest

that dust exposure was an important confounder or modified the effect.[Armstrong B et al; Environmental health perspectives 112 (9): 970-978 (2004). Available from, as of November 23,2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/15198916?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ Polycyclic aromatic hydrocarbons (PAHs) such as benzo[a]pyrene (BaP) are widespread air contaminants released by transportation vehicles, power generation, and other combustion sources. Experimental evidence indicates that the developing fetus is more susceptible than the adult to carcinogenic effects of PAHs, although laboratory studies in rodents suggest that the dose to fetal tissues is an order of magnitude lower than that to maternal tissues. To assess fetal versus adult susceptibility to PAHs and environmental tobacco smoke (ETS), ... carcinogen-DNA adducts (a biomarker associated with increased cancer risk) and cotinine (a biomarker of tobacco smoke exposure) /were compared/ in paired blood samples collected from mothers and newborns in New York City. ... 265 nonsmoker African-American and Latina mother-newborn pairs /were enrolled/ in New York City between 1997 and 2001 (estimated average ambient air BaP concentrations < 0.5 ng/cu m). Despite the estimated 10-fold lower fetal dose, mean levels of BaP-DNA adducts as determined by high-performance liquid chromatography-fluorescence were comparable in paired New York City newborn and maternal samples (0.24 adducts per 10(8) nucleotides, 45% of newborns with detectable adducts vs. 0.22 per 10(8) nucleotides, 41% of mothers with detectable adducts). However, by the Wilcoxon signed-rank test, the levels in newborns were higher (p = 0.02). Mean cotinine was higher in newborns than in mothers (1.7 ng/mL, 47% detectable vs. 1.28 ng/mL, 44% detectable). Consistent with a prior study in a Caucasian Polish population, these results indicate increased susceptibility of the fetus to DNA damage and reduced ability to clear ETS constituents. The findings have implications for risk assessment, given the need to protect children as a sensitive subset of the population.[Perera FP et al; Environmental Health Perspectives 112 (10): 1133-1136 (2004). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/15238289?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ Oral premalignant lesions (OPLs) are related to tobacco use and mark individuals at high risk for oral cancer development. Increased mutagen sensitivity as measured by an in vitro mutagen challenge assay has been shown to be a risk factor for upper aerodigestive tract cancers. This case control study used two assays with mutagens relevant to tobacco exposure (benzo[a]pyrene diol epoxide (BPDE) and bleomycin) to see whether sensitivity to these mutagens could be used as biomarkers for assessing risk of premalignant lesions. ... Whether 3p21.3 is a molecular target of BPDE damage in lymphocytes of patients with OPLs /was also evaluated/. There were 82 patients with OPLs and 89 healthy controls frequency matched to the cases on age, sex, ethnicity, and smoking status. These subjects' lymphocytes were treated in two separate experiments with either 2 uM BPDE for 24 hr or 0.03 units/mL bleomycin for 5 hr, and the frequency of induced chromatid breakage in Giemsa-stained preparations was determined. BPDE-induced 3p21.3 aberrations were scored by fluorescent in situ hybridization technique in 1000 interphases/sample. ...The mean BPDE-induced chromatid breaks per cell were higher in cases than controls (1.05 +/- 0.40 and 0.55 +/- 0.27, respectively; P < 0.01). Similar results were evident with bleomycin-induced chromatid breaks per cell (0.78 +/- 0.37 and 0.57 +/- 0.31, respectively; P < 0.01). After adjusting for age, sex, ethnicity, and smoking status, significantly elevated odds ratios (95% confidence interval) for OPL risk were noted for

BPDE sensitivity [12.96 (5.51, 30.46)] and bleomycin sensitivity [3.33 (1.64, 6.77)]. When subjects were categorized into quartiles of the number of breaks per cell, a dose response was observed for both assays. The adjusted odds ratios for subjects with increasing numbers of breaks per cell in quartiles were 2.34, 9.14, and 54.04 for BPDE sensitivity and 1.92, 3.33, and 7.15 for bleomycin sensitivity, respectively. Subjects sensitive to both mutagens had a 50-fold increased risk for OPLs. In addition, there were significantly more BPDE-induced chromosome aberrations at the 3p21.3 locus in cases (51.13/1000) than in controls (40.93/1000; P < 0.0001). However, no such difference was observed for 3q13, a control locus. BPDE-induced 3p21.3 aberrations were associated with an elevated risk for OPLs of 6.08 (2.57, 14.4). The degree of BPDE sensitivity at 3p21.3 and risk for OPLs increased in a dose-dependent manner. In summary, BDPE sensitivity and bleomycin sensitivity appear to be individually and jointly associated with elevated risk of OPLs. Furthermore, 3p21.3 may be a molecular target of BPDE in OPLs... /Benzo[a]pyrene diol epoxide/[Wu X et al; Cancer research 62 (10): 2813-2818 (2002). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/12019158?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ Human microsomal epoxide hydrolase (mEH) catalyzes a key step in the biotransformation of benzo[a]pyrene that yields the highly mutagenic (+)-anti-7,8-diol-9,10 epoxide (BPDE). Two polymorphisms have been described in the coding region of the mEH gene (EPHX1) that produce two protein variants: 113Tyr-- > 113His (exon 3) and 139His-- > 139Arg (exon 4). A case-control study among Northwestern Mediterranean Caucasians /was performed/ to investigate a possible association between these EPHX1 variants and lung cancer risk. Both EPHX1 polymorphisms were analyzed in a group of lung cancer patients (n=176) and in a control group of healthy smokers (n=187). The results showed a significantly decreased risk for the rare homozygous 113His/113His (adjusted odds ratio (OR): 0.44, 95% confidence interval (CI): 0.27-0.71) and 139Arg/139Arg (adjusted OR: 0.55, 95% CI: 0.33-0.91) compared with the major wild-types 113Tyr/113Tyr and 139His/139His, respectively, as the references. Thereafter, ... the EPHX1 variants /were analyzed/ in combination with three glutathione S-transferase polymorphic genes (GSTM1, GSTT1, and GSTP1) and we found a significant overepresentation of cancer patients with a combination of exon 3 113Tyr/113Tyr EPHX1 and exon 5 105Ile/105Ile GSTP1 (adjusted OR: 2.34, 95% CI: 1.21-4.52). The polymorphic site within the exon 5 of GSTP1 results in a Ile-- > Val substitution, and the isoleucine GSTpi isoform has been found in vitro to be less active than the valine isoform towards the conjugation of BPDE. The 113 Tyr/Tyr EPHX1 encodes for a high-activity mEH. /These/ results agree with observations in vitro and suggest that a genetically determined combination of a high-activity mEH and a low-activity GSTpi may increase lung cancer risk among smokers.[To-Figueras J et al; Cancer letters 173 (2): 155-162 (2001). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/11597790?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ ... PAH-DNA adducts /were measured/ as exposure and susceptibility markers together with genetic polymorphism in drug-metabolizing enzymes related to CYP1A1, GSTM1, and GSTT1 genes in case-control studies. (+)-anti-benzo[a]pyrene diol-epoxide (BPDE)-DNA adduct levels were quantitated in white blood cells (WBCs) and lung tissue DNA. CYP1A1 polymorphism and GSTM1 or GSTT1 gene deletion was analyzed in genomic DNA from lung parenchyma, WBCs, or oral biopsies (leukoplakia

patients from India) and from oral exfoliated cells (healthy controls). Results from lung cancer patients and PAH-exposed coke oven workers correlated CYP1A1-GSTM1 genotype combinations with BPDE-DNA adduct levels. Smokers with homozygous CYP1A1 variant and GSTM1 null had the highest adduct levels and were, as shown in Japanese smokers, most susceptible to lung cancer. In oral premalignant leukoplakia cases associated with betel quid/tobacco chewing, the prevalence of the GSTM1 null and GSTT1 null genotypes was significantly higher, as compared to healthy controls. The combined GST null genotypes prevailed in 60% of the cases with none detected in controls. Based on this short review it was concluded/ that (i) BPDE-DNA adduct levels resulting from "at risk" genotype combinations may serve as markers to identify most susceptible individuals; (ii) in Indian betel quid/tobacco chewers, the null genotypes of GSTM1 and GSTT1 greatly increased the risk for developing oral leukoplakia. /Benzo[a]pyrene diol-epoxide/[Bartsch H et al; Cancer Detection and Prevention 23 (6): 445-453 (1999). Available from, as of November 23,2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/10571654?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ To test the hypothesis that individual susceptibility to carcinogen exposure is a risk factor for breast cancer, /investigators/ measured DNA adduct formation in normal breast tissues treated in vitro with 4 uM benzo[a]pyrene in 76 cancer cases and 60 noncancer controls. A significantly higher level of adducts (134.6 +/21.2/10+9) /was found/among cases compared with controls (66.9 +/- 7.5; P = 0.007). The level of adducts was significantly associated with the risk of breast cancer (odds ratio, 4.38; 95% confidence interval, 1.04 to 18.50; P = 0.044) after adjusting for confounders. Stratified analysis and regression analysis demonstrated that race, pack-years of smoking, family history of breast cancer, and CYP1B1 genotype were significant predictors of the level of benzo[a]pyrene-induced adducts in the breast tissues. These observations suggest that genetic susceptibility to carcinogen exposure may play an important role in breast carcinogenesis.[Li D et al; Cancer research 62 (16): 4566-4570 (2002). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/12183407?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ Levels of DNA adducts vary greatly in vivo, attributable to individual differences in enzymatic bioactivation of benzo(a)pyrene. /Investigators/ developed an assay to measure the levels of DNA adducts induced in vitro by benzo(a)pyrene diol epoxide (BPDE), a bioactivated form of benzo(a)pyrene. In this large molecular epidemiological study of lung cancer, /the authors/ tested the hypothesis that the level of in vitro BPDE-induced adducts is associated with risk of lung cancer. This hospital-based case-control study included 221 newly diagnosed lung cancer cases and 229 healthy controls frequency matched on age, sex, ethnicity, and smoking status. Short-term cultured peripheral blood lymphocytes from each subject were exposed in vitro to BPDE (4 microm) for 5 h, and the 32P-postlabeling method was then used to measure BPDE-induced DNA adducts in the host cells. Overall, the patients had significantly higher levels of BPDE-DNA adducts than did the controls (mean +/- SD per 10+7 nucleotides, 93.2+/-89.3 for cases versus 63.7+/-61.1 for controls; P = 0.001). Univariate and multivariate logistic regression analyses were performed to calculate the crude and adjusted odds ratios and their 95% confidence intervals. When the median adduct level of controls (46/10+7 nucleotides) was used as the cutoff point, 64% of cases had higher levels (odds ratio, 2.15; 95% confidence interval, 1.39-3.33, adjusted for age, sex, ethnicity, body mass index, recent

weight loss, pack-years smoked, smoking in the last 24 h, and family history of cancer). Stratified analyses showed consistently higher levels of BPDE-induced adducts in cases than in controls, regardless of subgroup of age, sex, ethnicity, body mass index, recent weight loss, pack-years smoked, smoking in the last 24 h, and family history of cancer. A significant dose-response relationship between the quartile levels of BPDE-induced DNA adducts and the risk of lung cancer was observed (trend test, P < 0.001). The significant association between the level of in vitro BPDE-induced DNA adducts and risk for lung cancer suggests that subjects very sensitive to BPDE-induced DNA damage may have a suboptimal ability to remove the BPDE-DNA adducts and so are susceptible to tobacco carcinogen exposure and, therefore, may be at increased risk of lung cancer. /Benzo(a)pyrene diol epoxide/[Li D et al; Cancer research 61 (4): 1445-1450 (2001). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/11245449?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ Microsomal epoxide hydrolase participates in the metabolism of benzo[a]pyrene, an important carcinogen in tobacco smoke. Two relatively common polymorphisms of the microsomal epoxide hydrolase gene that influence enzyme activity have been described. An association between genetic variation in microsomal epoxide hydrolase and lung cancer risk has been reported in one of two studies of Caucasians. ... The relation between these two polymorphisms and lung cancer risk /was examined/ among 337 incident cases and 700 population controls of African-American and Caucasian ethnicity enrolled in a case-control study in Los Angeles County. African-Americans, homozygous for the exon 3 variant allele conferring reduced activity, were at decreased risk of lung cancer (odds ratio (OR)=0.08, 95% CI 0.01-0.62). When data from both the exon 3 and exon 4 polymorphisms were combined into indices of predicted microsomal epoxide hydrolase activity, a decreased risk was seen among African-American subjects with very low predicted activity OR=0.10 (95% CI 0.01-0.83). No comparable association was seen among Caucasians. Although the three published results for Caucasians are somewhat variable, the association among African-Americans in these data provides some support for the hypothesis that genetically reduced microsomal epoxide hydrolase activity may be protective against lung cancer.[London SJ et al; Lung cancer (Amsterdam, Netherlands) 28 (2): 147-155 (2000). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/10717332?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ In a case-control study, /investigators/ recruited case subjects who were previously treated with surgery and/or radiotherapy for stage I or stage II squamous cell carcinoma of the head and neck to test the hypothesis that lymphocytic chromatid breaks induced by benzo[a]pyrene diol epoxide (BPDE), a tobacco mutagen, may also be associated with risk of developing cancers of the upper aerodigestive tract. Case subjects were matched to control subjects on the basis of age, sex, ethnicity, and smoking status. Primary lymphocytes from 67 case subjects and 81 control subjects were treated with 2 microM BPDE for 24 hours, and the frequency of induced chromatid breaks was determined. All statistical tests were two-sided. Lymphocytes from case subjects compared with lymphocytes from control subjects showed significantly more breaks per cell induced by BPDE (mean+/-standard deviation, 0.77+/-0.38 versus 0.49+/-0.25; P < .001). Lymphocytes from 64.2% of case subjects were sensitive to BPDE (using a cutoff value of > or =0.60 break per cell). Subjects in the highest quartile of chromatid breaks had an approximately 20-fold increased risk of cancer compared with those in the lowest

quartile after adjustment for age, sex, ethnicity, and smoking status. The association between BPDE sensitivity and cancer risk was higher in former smokers than in current smokers and higher in younger patients than in older patients. Subjects with sensitivity to both BPDE and bleomycin were at a 19.2-fold increased risk of cancer compared with those who were not sensitive to either agent. Mutagen sensitivity assays may aid in identifying individuals at risk of cancer, and use of parallel assays with two mutagens may improve risk predictability. /Benzo[a]pyrene diol epoxide/[Wu X et al; Journal of the National Cancer Institute 90 (18): 1393-1399 (1998). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/9747870?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ ... Benzo[a]pyrene diol-epoxide (BPDE)-induced mutagen sensitivity and polymorphisms of GSTM1 and GSTT1 /wre analyzed/ in a pilot case-control study of breast cancer. Short-term cell cultures were established from blood samples of 100 female breast cancer patients and 105 healthy controls. After 5 hr of in vitro exposure to 4 uM of BPDE, lymphocytes /wre harvested/ for cytogenetic evaluation and recorded and compared the frequency of BPDE-induced chromatid breaks between cases and controls. ... Cases had a significantly higher frequency of chromatid breaks than did controls (P < 0.0001). The level of chromatid breaks greater than the median value of controls was associated with a > 3-fold increased risk of breast cancer [adjusted odds ratio (ORadj) = 3.11; 95% CI = 1.72-5.64]. The risk was more pronounced in those who were < 45 years (ORadj = 4.79; 95% CI = 1.87-12.3), ever-smokers (ORadj = 5.55; 95% CI = 1.85-16.6), alcohol drinkers (ORadj = 4.64; 95% CI = 1.70-12.7), and those who had the GSTT1 null variant (ORadj = 8.01; 95% CI = 1.16-55.3). These data suggest that sensitivity to BPDE-induced chromosomal aberrations may contribute to the risk of developing breast cancer, and such sensitivity may be modulated by both genetic and environmental factors. /Benzo[a]pyrene diol-epoxide/[Xiong P et al; Cancer research 61 (23): 8465-8469 (2001). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/11731429?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/... /The/ objective was to evaluate the association between the benzo[a]pyrene diol epoxide (BPDE)-induced chromatid breaks per cell (b/c) values and the risk of squamous cell carcinoma of the head and neck (SCCHN) in a pilot case-control study. Blood samples were obtained from 60 SCCHN patients and 112 healthy controls matched for age, sex, ethnicity, and smoking status. After incubation and exposure to BPDE, metaphase spread slides were created, and the average b/c values were determined. Univariate analysis identified elevated BPDE-induced b/c values as a significant risk factor [P < 0.05, crude odds ratio (OR)=1.94, 95% confidence interval (CI)=1.00-3.74]. On multivariate analysis using logistic regression models and including age, sex, ethnicity, and smoking status, BPDE-induced b/c values remained an independent risk factor for disease (P < 0.05, adjusted OR=2.36, 95% CI=1.17-4.79). Furthermore, when b/c values were divided based on control values into low, medium, and high tertiles, there was a dose-response relationship: an adjusted OR of 1.28 (95% CI=0.49-3.33) for the middle tertile and an adjusted OR of 4.09 (95% CI=1.67-10.0) for the high tertile (trend test, P < 0.001). ... /Benzo[a]pyrene diol epoxide/[Wang LE et al; Clinical cancer research: an official journal of the American Association for Cancer Research 4 (7): 1773-1778 (1998). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/9676854?dopt=Abstract"

target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ The almost twofold difference in lung cancer incidence between people living in Copenhagen and in rural area of Denmark in the 1980s led to public concern; this study was undertaken to assess the effects of air pollution and occupation on lung cancer in Denmark, with control for smoking habits. Cohort study of national population. People aged 30-64 and economically active in 1970 (927,470 men and 486,130 women). Relative risks for lung cancer estimated with multiplicative Poisson modelling of incidence rates. Differences in smoking habit explained about 60% of the excess lung cancer risk in Copenhagen for men and 90% for women. After control for smoking, workers had double the lung cancer risk of teachers and academics. There was only a small independent effect of region. Smoking is the main factor behind the regional differences in lung cancer incidence in Denmark, and occupational risk factors also seem to have an important role. The outdoor air in Copenhagen around 1970 contained on average 50-80 micrograms/cu m of sulfur dioxide, 80-100 micrograms/cu m total suspended particulate matter, and up to 10 ng/cu m benzo[a]pyrene and had peak values of daily smoke of 120 micrograms/cu m.[Engholm G et al; BMJ 312 (7041): 1259-63 (1996). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/8634614?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ Nested case-control interview studies of lung cancer (610 incident cases), stomach cancer (292 incident cases), and 959 controls were conducted to follow up leads from a proportional mortality analysis of deaths among male workers in a large integrated iron-steel complex in Anshan, China. For lung cancer, after adjusting for the significant non-occupational risk factors (smoking, other pulmonary disease, family history of lung cancer, and low consumption of fruit or tea), risks were significantly elevated for those employed for 15 or more years in smelting and rolling (OR = 1.5, CI = 1.1-2.2), in the fire-resistant brick factory (OR = 2.9, CI = 1.4-5.9), in general loading (OR = 2.5, CI = 1.0-6.1), and as coke oven workers (OR = 3.4; CI = 1.4-8.5). For stomach cancer, after adjusting for consumption of pickled vegetables, prior gastric diseases, family history of stomach cancer, low intake of fruits and vegetables, and education, risks were significantly elevated for those employed for 15 or more years in ore sintering and transportation (OR = 2.1, CI = 1.0-4.4), in the fire-resistant brick factory (OR = 2.5, CI = 1.1-5.8), in general loading (OR = 3.2, CI = 1.2-8.9), as boilerworkers and cooks (OR = 2.6, CI = 1.2-5.6), and as coke oven workers (OR = 5.4, CI = 1.8-16.0). For both lung and stomach cancers, significant dose-response gradients were observed for exposure to total dust and benzo(a)pyrene, but not for specific chemical components of dust. Overall, long-term steel workers with exposure to workplace pollutants had a 40% increased risk of both lung and stomach cancers.[Xu Z et al; American journal of industrial medicine 30 (1): 7-15 (1996). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/8837676?dopt=Abstract" target=new>PubMed Abstract /EPIDEMIOLOGY STUDIES/ Mortality and cancer incidence were investigated among 901 workers at a Swedish company manufacturing graphite electrodes. Current and previous measurements of personal exposure to benzo[a]pyrene were used to calculate individual exposure estimates. Smoking habits were investigated by questionnaire. There were 42 deaths during the study period (1968-1989), whereas 32.3 would be expected, based on age, sex, time, and county-specific population statistics. Three cancers of the respiratory system were found vs 1.2 expected. The overall mortality was

slightly elevated, mainly due to an increased number of deaths from external causes. Thus far, no excess risk of cancer has been documented in this cohort. The results indicate that an increased risk of respiratory cancer may be present, but influence from chance cannot be ruled out due to small numbers. ...[Gustavsson P et al; Environmental research 70 (1): 7-10 (1995). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/8603661?dopt=Abstract" target=new>PubMed Abstract /SURVEILLANCE/ The uptake of polycyclic aromatic hydrocarbons (PAH) in nurses who apply ointments containing coal tar to patients and the effectiveness of skin protection methods /were investigated/. ... Inhalation of airborne pyrene and benzo[a]pyrene /were ruled out/ as the sources of PAH exposure. However, substantial amounts of pyrene and benzo[a]pyrene were observed on the hands of the nurses (median 33.0 and 16.4 ng/sq cm, respectively). Excretion of urinary 1-hydroxypyrene indicated an increased uptake of pyrene in 8 out of 12 nurses. /The authors/ asked 35 nurses to perform a treatment with gloves followed by a second treatment without gloves. The use of gloves changed the excretion of 1-hydroxypyrene by -0.58 umol (range -5.1-1.0 umol), corresponding to a median reduction of 51.5% (P < 0.001). Based on this finding, a new protocol was adopted, involving the permanent use of vinyl gloves and Tyvek sleeves. The effectiveness of this protocol was tested against pre-existing work practices and showed a 97% reduction in skin contamination with pyrene and benzo[a]pyrene, and a lowering in urinary excretion of 1-hydroxypyrene of 57%. Protecting the skin more stringently reduced pyrene and benzo[a]pyrene contamination of the hands, and lowered urinary excretion of 1-hydroxypyrene.[Scheepers, P et al; Scandinavian Journal of Work, Environment &amp; Health 35 (3): 212-221 (2009). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/19430709?dopt=Abstract" target=new>PubMed Abstract /SURVEILLANCE/ To study possible mutational changes associated with smoking as a risk factor for lung cancer, ... HPRT mutations in T-cells of newly diagnosed, nonsmoking and smoking lung cancer patients /were analyzed/ before treatment. Reverse transcriptase polymerase chain reaction (RT-PCR) and DNA sequencing methods were used to identify 146 independent mutations, 73 each from 32 nonsmoking and 31 smoking cases. In 35 T-cell mutants, the HPRT cDNA showed loss of an entire exon, indicating a splicing mutation. Among the remaining 111 fully characterized mutations in the coding region, single base pair (bp) substitutions predominated with 79% (48/61) in nonsmokers and 90% (45/50) in smokers. Frameshift and small deletion (1-24 bp) mutations were found in 18 mutants. The distribution of base pair substitutions was nonrandom, with significant clustering at previously identified hotspot positions 143, 197 and 617 in the HPRT coding sequence (P < or =0.008). One additional hotspot, GC-- > TA at position 606, was observed only in smokers (P=0.006). The frequency of GC > TA transversions was higher in smokers (13%) than in nonsmokers (6%). Conversely, smokers had a lower frequency of GC > AT transitions (24%) than nonsmokers (35%). This smoking-associated shift of the HPRT mutational spectrum, although not statistically significant, is consistent with the in vitro mutagenicity of benzo[a]pyrene (BaP), a prominent carcinogen of tobacco smoke, and with known differences in the TP53 mutational spectrum in lung tumors of smokers and nonsmokers. Among nonsmokers, the HPRT mutational spectra in healthy population controls and lung cancer patients were similar, but there was a marginally significant difference (P=0.07) in the distribution of base pair substitutions between smoking controls and patients. These results suggest that (i) general mechanisms of somatic mutagenesis in individuals with possible

predisposition to cancer (e.g. nonsmoking lung cancer patients) are not different from those in normal healthy individuals, and (ii) the HPRT gene in T-cells is a useful reporter locus for smoking-associated somatic in vivo mutations occurring early in lung cancer development.[Hackman P et al; Mutation research 468 (1): 45-61 (2000). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/10863157?dopt=Abstract" target=new>PubMed Abstract /BIOMONITORING/ Urinary metabolites of tobacco smoke toxins are often used as biomarkers for the evaluation of active and passive exposure to cigarette smoke toxins. In a study of healthy smokers, /The authors/ investigated concentrations of urinary biomarkers in relation to concentrations of selected toxins in mainstream cigarette smoke as determined by machine smoking of cigarettes in a manner that mimics an individual's smoking behavior (topography). Concentrations of nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, and benzo[a]pyrene, in mainstream smoke determined under human smoking conditions, and their urinary metabolites cotinine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, and 1-hydroxypyrene were established for 257 individuals who smoked low-yield (0.1-0.8 mg Federal Trade Commission nicotine/cigarette; mean, 0.66; n = 87), medium-yield (0.9-1.2 mg nicotine/cigarette; mean, 1.1; n = 109), and high-yield cigarettes (nicotine, > 1.3 mg nicotine/cigarette; mean, 1.41; n = 61). Levels of urinary metabolites expressed per unit of delivered parent compounds decreased with increased smoke emissions. In smokers of low-, medium-, and high-yield cigarettes, the respective cotinine (ng/mg creatinine)-to-nicotine (mg/d) ratios were 89.4, 77.8, and 57.1 (low versus high; P = 0.06); the 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (pmol/mg creatinine)-to-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (ng/d) ratios were 0.81, 0.55, and 0.57 (low versus high; P = 0.05); and the 1-hydroxypyrene (pg/mg creatinine)-to-benzo(a)pyrene (ng/d) ratios were 1.55, 1.13, and 0.97 (low versus high; P = 0.008). Similarly, means of cotinine per unit of delivered nicotine in smokers who consumed < 20 cigarettes per day was 3.5-fold higher than in those who smoked > 20 cigarettes per day. Likewise, a negative correlation was observed between cotinine-to-nicotine ratios and delivered doses of nicotine in subgroups of smokers who used the identical brand of cigarette, namely a filter tip-vented Marlboro (r = -0.59), which is a popular brand among Euro-Americans, and Newport (r = -0.37), a menthol-flavored cigarette without filter tip vents that is preferred by African-Americans. Thus, the intensity of the exposures significantly affects the levels of urinary biomarkers of exposure and should be taken into account in the evaluation of human exposure to cigarette smoke toxins.[Melikian, AA et al; Cancer Epidemiology, Biomarkers &amp; Prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 16 (7): 1408-15 (2007). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/17627005?dopt=Abstract" target=new>PubMed Abstract /BIOMONITORING/ An increase in immunoglobulin (Ig) A isotype directed against benzo[a]pyrene (BP) structure has previously been described in sera of cancer patients. In this study, new polycyclic aromatic hydrocarbon (PAH) conjugates were synthesized in order to more closely mimic the endogenous ligands of the cytosolic aryl hydrocarbon receptor (AhR). PAH [benzo[a]pyrene; 1,2-benzanthracene; dibenz[a,c]anthracene; 7,12-dimethylbenza[a]anthracene; benzo(ghi)perylene] were bound to protein carriers such as bovine serum albumin (BSA) via N-acetyl-cysteine (NAC). The levels of circulating antibodies (Abs) directed against PAH-NAC

conjugates in the sera of cancer patients were evaluated using an Enzyme-Linked Immunosorbent Assay (ELISA) with these new conjugates. The avidity (IC(50)) and specificity of these circulating Abs were assessed via competition experiments. An increase in Ig directed against these PAH-NAC conjugates was found in the sera of cancer patients, irrespective of the state and stage of the tumors. These Ig were principally of the A isotype. Sera from cancer patients had significantly higher optical density (OD) ranges than the controls, p < 0.0001. The ELISA test for breast cancer (n=155) and ovarian cancer (n=62) identified 82% and 92% of positive patients, respectively. The percentage positive in the control group (n=60) was around 5%. Moreover, competition experiments with the different PAH-NAC conjugates and NAC-BSA revealed an estimated avidity of 10-6 M for the circulating IgA antibodies. The Abs discriminated between the different PAH-NAC conjugates and NAC-BSA. Therefore, these Abs recognize a carcinogenic PAH-NAC structure and not only a BP structure. These markers may be useful in the future for monitoring cancer evolution and recurrence.[Pouns O et al; Cancer epidemiology 33 (1): 3-8 (2009). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/19679040?dopt=Abstract" target=new>PubMed Abstract /BIOMONITORING/ The benzo[a]pyrene (BaP) metabolite benzo[a]pyrenediolepoxide (BPDE) is strongly implicated as a causative agent of lung cancer. To assess the risk of exposure to BaP, /investigators/ made a combined analysis of levels of BPDE adducts to hemoglobin (Hb), serum albumin (SA), and lymphocyte DNA in 44 patients with incident lung cancer, as a prototype of a population mainly exposed to tobacco-derived BaP. /The authors/ also investigated whether genetic polymorphisms of cytochrome P450IA1 (CYPIA1), microsomal epoxide hydrolase (mEH), and glutathione S-transferase M1 (GSTM1), which are involved in BaP metabolism, can be determinants of adduct formation. BPDE-Hb, BPDE-SA, and BPDE-DNA adducts were quantified as BaP tetrols released from hydrolysis of macromolecules and measured by high-resolution gas chromatography-negative ion chemical ionization-mass spectrometry to achieve high specificity and sensitivity. Individuals with detectable Hb adducts were positive for SA adducts but not vice versa, suggesting that BPDE-Hb adducts are less informative indicators of BaP exposure. Using PCR methods on DNA, we characterized GSTM1 deletion, CYPIA1 MspI and exon 7 valine variants, and mEH polymorphisms at amino acid positions 113 (EH3) and 139 (EH4). Levels of BPDE adducts were no different among CYPIA1, mEH, and GSTM1 genotypes. However, individuals with measurable BPDE-SA adducts were CYPIA1 variant carriers more frequently (P = 0.03). There was a slightly higher percentage of DNA detectable adducts in subjects with CYPIA1 exon 7 valine polymorphism. When subjects were classified by both polymorphisms on the mEH gene, those with two slow alleles (EH3 homozygous mutated) and no fast alleles (EH4 homozygous wild type) had a lower frequency of BPDE-SA adducts and no DNA adducts (P = 0.06). These results are based on a small number of observations thus far, but this exploratory study suggests that CYPIA1 and mEH variants might have an impact on BPDE exposure markers such as BPDE-SA adducts. Chemical specificity in adduct measurements is important to identify the biomarkers that reflect BaP exposure more accurately.[Pastorelli, R et al; Cancer Epidemiology, Biomarkers &amp; Prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 7 (8): 703-709 (1998). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/9718223?dopt=Abstract" target=new>PubMed Abstract /BIOMONITORING/ /The authors/ conducted a cross-sectional molecular

epidemiological study of coke oven workers exposed to the established carcinogen polycyclic aromatic hydrocarbons (PAHs) to evaluate the relationships between both traditional 'exposure markers' and a series of biomarkers, including urinary 1-hydroxypyrene as a marker of internal dose, leukocyte aromatic DNA adducts as markers of biologically effective dose, serum p53 protein as a response marker and genetic polymorphisms of cytochrome P4501A1 and glutathione S-transferase MI as susceptibility markers. Twenty-five male subjects each were randomly selected from the top, middle and bottom work areas of the oven, and the control plant. They were matched for age and smoking status. The mean levels of PAH exposure, monitored by stationary and personal samplers, and of worker urinary 1-hydroxypyrene differed significantly between the top, middle and bottom of the oven and control work areas. The highest stationary and personal PAH concentrations and 1-hydroxypyrene levels were demonstrated at the top work area. Good correlations were found between the stationary PAH levels, personal PAH levels and urinary 1-hydroxypyrene levels. No positive correlations were demonstrated between aromatic DNA adduct levels and current or cumulative PAH exposure dose. In the presence of genetic polymorphisms of cytochrome P4501A1, a positive correlation was demonstrated between aromatic DNA adducts and urinary 1-hydroxypyrene levels. There was also a significant correlation between serum p53 protein levels and the cumulated benzo[a]pyrene exposure dose. Although these biomarkers have certain limitations, they are applicable to cancer epidemiology, and may contribute to our understanding of the mechanisms of carcinogenesis.[Pan G et al; Carcinogenesis 19 (11): 1963-1968 (1998). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/9855010?dopt=Abstract" target=new>PubMed Abstract /BIOMONITORING/ In a field study with 69 subjects, /the authors/ investigated the influence of smoking, exposure to environmental tobacco smoke (ETS), diet, and location of residence on biomarkers for polycyclic aromatic hydrocarbons (PAH), including urinary excretion of 1-hydroxypyrene and benzo[a]pyrene (BaP) adducts of hemoglobin and albumin. The self-reported smoking status and the extent of ETS exposure were verified by urinary cotinine measurements. ETS exposure was quantified by nicotine and 3-ethenylpyridine measurements on personal samplers worn by the nonsmokers over 5 or 7 days before blood and urine samples were collected. Smokers (n = 27), on average, excreted 0.346 ug/24 hr 1-hydroxypyrene, whereas the corresponding value for nonsmokers (n = 42) was 0.157 ug/24 hr. Average BaP adduct levels with hemoglobin and albumin were 0.105 fmol/mg and 0.042 fmol/mg, respectively, for smokers, and 0.068 fmol/mg and 0.020 fmol/mg, respectively, for nonsmokers. The differences, except for the hemoglobin adducts, were statistically significant. Of the 42 nonsmokers, 19 were classified as passive smokers. There was no significant difference in the PAH biomarkers between nonsmokers exposed to ETS and those not or rarely exposed to ETS. Total dietary BaP intake, as calculated from questionnaire data, did not correlate with any of the PAH biomarkers (r < 0.1). Subjects living in the suburbs tended to have higher BaP-protein adduct levels than subjects living in the city. Our findings suggest that diet and smoking are major sources for PAH exposure of persons not occupationally exposed to PAH, whereas the influence of ETS exposure is negligible. The lack of correlation between the dietary PAH intake and the PAH biomarkers may be due to the inaccuracy of the estimate for the dietary PAH intake.[Scherer G et al; Cancer Epidemiology, Biomarkers &amp; Prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 9 (4): 373-380 (2000). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/10794481?dopt=Abstract"

target=new>PubMed Abstract /BIOMONITORING/ Coke-oven workers are occupationally exposed to a high concentration of polycyclic aromatic hydrocarbons (PAH). r-7,t-8,9,c-10-Tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (trans-anti-BaP-tetraol) and 1-hydroxypyrene (1-OHP) are urinary metabolites of benzo(a)pyrene and pyrene, respectively. This study investigated the relationship among individual air exposure to benzene soluble fraction (BSF) of total particulates, as a surrogate marker of ambient PAH exposures, and urinary trans-anti-BaP-tetraol and 1-OHP concentrations in coke-oven workers at a steel plant in Taiwan. Fifty-seven subjects, including 41 male workers who work in one coke-oven plant and 16 men (referents) from an administrative area, were studied. The mean trans-anti-BaP-tetraol and 1-OHP concentrations (mean +/- SD) were 0.4 +/- 0.3 nmol/mol creatinine and 9.7 +/- 21.6 micromol/mol creatinine, respectively, in coke-oven workers. These levels were significantly higher than those in referents (0.03 +/- 0.03 nmol/mole creatinine, P < 0.001 and 0.4 +/- 0.2 umol/mol creatinine, P < 0.01, respectively). Urinary trans-anti-BaP-tetraol concentrations were significantly and positively correlated with individual average BSF and urinary 1-OHP concentrations. That is, the higher the urinary trans-anti-BaP-tetraol concentrations, the more ambient BSF exposure and urinary 1-OHP concentrations (Spearman correlation coefficients r = 0.68 and 0.70, respectively; P < 0.0001; n = 57). These findings suggest that urinary 1-OHP and trans-anti-BaP-tetraol might be considered as potential biomarkers for the assessment of uptake of known PAH carcinogens in the air. /trans-anti-BaP-tetrol/[Wu MT et al; Cancer Epidemiology, Biomarkers &amp; Prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 11 (3): 311-314 (2002). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/11895883?dopt=Abstract" target=new>PubMed Abstract /BIOMONITORING/ Environmental monitoring should take into account the technological cycle and the tasks with higher PAH exposure risk, and the main sources of emissions. In the case of skin contamination, it should be considered the measure of skin PAH by means of sampling or removal techniques; moreover, the determination of urinary hydroxypyrene (1-HP) should be performed. It is mandatory to analyse (Benz[a]) anthracene; Benzo[b]fluroanthene; Benzo[j]fluoranthene; Benzo[k]fluoranthene; Benzo[a]pyrene; Dibenzo[a,h]anthracene, ie the PAH marked with the R45-R49 phrase. When 1-HP determination is planned, Pyrene should be added. Biological monitoring has been addressed mainly to hydroxylated metabolites of pyrene and among these 1-HP, the main metabolite of pyrene, although non occupational factors, such as tobacco smoking and consumption of smoked foods are potentially confounding. Urinary mutagenicity tests which are heavily influenced by non occupational factors such as tobacco smoking and diet are not advisable. The determination of DNA and protein adducts is a promising test for evaluation of metabolic active dose ...[Apostoli P et al; Giornale italiano di medicina del lavoro ed ergonomia 19 (4): 137-151 (1997). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/9775008?dopt=Abstract" target=new>PubMed Abstract /BIOMONITORING/ A cross-sectional study was conducted among 94 traffic police officers from the Municipality Police of Genoa, Italy, exposed to airborne pollutants and 52 referent subjects exposed to indoor air pollution levels to investigate the relationships between exposure to

ambient air polycyclic aromatic hydrocarbons (PAHs) and urinary excretion of 1-hydroxypyrene (1-OH-P). The effects of smoking, lifestyle factors such as exposure to ETS, and diet, along with the role played by the cytochrome P4501A1 (CYP1A1), and glutathione S-transferase M1 and theta metabolic susceptibility gene polymorphisms were examined. The geometric mean of benzo(a)pyrene air measurements (an index compound of PAH levels) was 70 times higher in traffic police officers (3.67 ng/cu m) than in referents (0.05 ng/cu m). The urinary concentration of 1-OH-P was clearly associated with cigarette smoking and, to a lesser extent, with exposure to ETS and particulate PAH pollution. No association was detected between 1-OH-P excretion and diet. Women exhibited a higher excretion level than did men, and an apparent effect of age was due to differences in cigarette smoking habits. Exposure to PAHs resulted in higher levels of 1-OH-P excretion in all groups except heavy smokers. Overall, no significant role of any metabolic polymorphism was detected. However, stratification of study subjects according to their smoking habits revealed higher levels of excretion of 1-OH-P in subjects smoking < or =15 cigarettes/day carrying the CYP1A1 polymorphism. No such effect was seen either with nonsmokers or with people smoking more than 15 cigarettes/day. These findings are suggestive of a gene-environment interaction, in which subjects with the CYP1A1 polymorphism, relative to subjects without it, have higher levels of 1-OH-P in their urine at low doses of exposure to PAHs.[Merlo F et al; Cancer Epidemiology, Biomarkers &amp; Prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 7 (2): 147-155 (1998). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/9488590?dopt=Abstract" target=new>PubMed Abstract /BIOMONITORING/ A method for the simultaneous determination of urinary phenanthrene, fluoranthene, pyrene, chrysene and benzo[a]pyrene metabolites has been developed for individual risk assessment at polycyclic aromatic hydrocarbon (PAH)-burdened workplaces. The concentration of urinary metabolites as a measure for individual PAH exposure takes account not only of PAH masses resorbed by the respiratory tract but also those incorporated percutaneously. The method allows the determination of 25 different components with a low margin of error; the individual metabolite profiles thereby allow conclusions on the individual characteristics of PAH-oxidizing enzymes (monooxygenases). The coefficients of variation are lower than 10%. After enzymatic treatment of the urine with glucuronidase and arylsulfatase one part of the benzene or toluene extract is treated with diazomethane to convert phenols into methylethers, while another part is used to convert dihydrodiols into phenols. After further purification the metabolites are determined by means of a combination of gas chromatography and mass spectrometry. The PAH exposure of coke plant workers during several consecutive days resulted in fairly constant individual urinary metabolite profiles which, however, exhibited significant inter-individual variability. This held true also for Wistar rats exposed to tar pitch aerosol on 5 days during a period of 10 days. It was also demonstrated that in the case of coke plant workers there is a correlation between inhaled PAH and metabolites excreted. Mass relationships between inhaled PAH and metabolites excreted were found to differ from one individual to another.[Grimmer G et al; International archives of occupational and environmental health 69 (4): 231-239 (1997). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/9137996?dopt=Abstract" target=new>PubMed Abstract /BIOMONITORING/ The aim was to assess the significance of two biomarkers;

antibody to benzo[a]pyrene DNA adducts and concentration of hydroxyethylvaline hemoglobin adducts in samples from a well studied group of coke oven workers. As a measure of exposure ... 1-hydroxypyrene in urine /was used/. Urine and blood samples were collected from coke oven workers and a control group. Samples from coke oven plant workers were collected in January and June. 1-Hydroxypyrene was measured in urine by high performance liquid chromatography (HPLC), antibodies to benzo[a]pyrene DNA adducts were measured by ELISA and hydroxyethylvaline hemoglobin adducts were measured by gas chromatography-mass spectrometry (GC-MS). Mean urinary 1-hydroxypyrene in samples from coke oven workers varied from 1.11 to 5.53 umol/mol creatinine and 0.14 umol/mol creatinine in the control group. Workers at the top side had the highest values of urinary 1-hydroxypyrene. Antibody to benzo[a]pyrene DNA adducts did not correlate with either 1-hydroxypyrene nor length of work at the coke oven plant. But antibody concentration in samples collected in January was predictive of the concentration in samples collected in June. A small non-significant increase in hydroxyethylvaline haemoglobin adducts was found in samples from coke oven workers relative to the control group when comparing smokers and nonsmokers separately. 1-Hydroxypyrene correlates well with exposure groups based on job description. Antibodies to benzo[a]-pyrene DNA adducts was related to people and not exposure. Work at a coke oven plant might lead to increased hydroxyethylvaline hemoglobin adducts.[Ovrebo S et al; Occupational and environmental medicine 52 (11): 750-756 (1995). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/8535495?dopt=Abstract" target=new>PubMed Abstract /BIOMONITORING/ Benzo[a]pyrene (BP) exposure causes alterations in gene expression in normal human mammary epithelial cells (NHMECs). This study used Affymetrix Hu-Gene133A arrays, with 14,500 genes represented, to evaluate modulation of BP-induced gene expression by chlorophyllin in six NHMEC strains derived from different donors. A major goal was to seek potential biomarkers of carcinogen exposure and how they behave in the presence of a chemopreventive agent. NHMECs (passage 6 and 70% confluence) were exposed for 24h to either vehicle control, or BP, or chlorophyllin followed by BP and chlorophyllin together. BP exposure resulted in approximately 3-fold altered expression of 49 genes in at least one of the six NHMEC strains. When cells were exposed to chlorophyllin pre-treatment followed by BP plus chlorophyllin, expression of 125 genes was similarly altered. Genes in the functional categories of xenobiotic metabolism, cell signaling, cell motility, cell proliferation, cellular transcription, metabolism, cell cycle control, apoptosis and DNA repair were identified. Only CYP1B1 and ALDH1A3 were consistently up-regulated by approximately 3-fold in most of the cell strains (at least 4) when exposed to BP. Cluster analysis identified a suite of 13 genes induced by BP where induction was mitigated in the presence of chlorophyllin. Additionally, cluster analysis identified a suite of 16 genes down-regulated by BP where induction was partially restored in the presence of chlorophyllin.[Kaarthik J et al; Mutation research 640 (1-2): 145-152 (2008). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/18336845?dopt=Abstract" target=new>PubMed Abstract /BIOMONITORING/ Workers in coke oven plants have a higher incidence of lung cancer than the general population. They are exposed to a variety of chemicals, in particular the polycyclic aromatic hydrocarbons (PAH), including benzo[a]pyrene. ... Since benzo[a]pyrene is activated to 7-beta,8-alpha-dihydroxy-(9-alpha,10-alpha)-epoxy-7,8,9,10-tetrahydrobenzo (a)pyrene

(BPDE) and binds to DNA, ultrasensitive enzymatic radioimmunoassay and synchronous fluorescence spectrophotometry /were used/ to measure BPDE-DNA adducts in lymphocyte DNA. The mean PAH exposure levels are reduced 60% when the workers wore masks during work. When compared to exposure levels, the urinary excretion of PAH was relatively low. Approximately one-third of the workers had detectable putative BPDE-DNA adducts in lymphocytes by ultrasensitive enzymatic radioimmunoassay, and 10% of the samples had emission peaks at 379 nm by synchronous fluorescence spectrophotometry. The four most positive samples were the same in both of the assays. Antibodies to an epitope(s) on BPDE-DNA were found in the sera of approximately one-third of the workers. Detection of DNA adducts and antibodies to these adducts are internal indicators of exposure to benzo[a]pyrene.[Haugen A et al; Cancer Res 46 (8): 4178-83 (1986)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/3731085?dopt=Abstract" target=new>PubMed Abstract /GENOTOXICITY/ To study the relationship between lymphocyte micronucleus rates and blood plasma levels of benzo[a]pyrene [BaP] in coking workers. One hundred coking workers and 100 unexposed workers were selected, and their lymphocyte micronucleus rates and plasma levels, as well as workplace air concentrations, of BaP were determined. It showed that there was significant difference in plasma BaP level between coking workers and unexposed workers, and it correlated with air concentration of BaP in the workplace. Positive rates of micronucleus and rates of micronucleus lymphocyte were 60% and 1.79 per thousand in coking workers and 29% and 1.10 per thousand in controls, respectively, with very significantly statistical difference. It also showed that positive micronucleus rate correlated with plasma level of BaP in dose-effect pattern. Multivariate analysis showed that factors contributing to positive micronucleus rate ranked in such an order: plasma level of B(a)P, economic status, regularity of their lifestyle and smoking status of the coking workers. Accumulation of BaP in blood plasma played a major role in the formation of lymphocyte micronucleus. Results of micronucleus test in coking workers could reflect preliminary damage to their health caused by it.[Wang G et al; Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] 33 (1): 40-42 (1999). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/11864455?dopt=Abstract" target=new>PubMed Abstract /GENOTOXICITY/ The mutagenicity of benzo[a]pyrene (B[a]P), dibenzo[a,e]pyrene (DB[ae]P), dibenzo[a,h]pyrene (DB[ah]P), dibenzo[a,i]pyrene (DB[ai]P), and dibenzo[a,l]pyrene (DB[al]P) was measured in quantitative forward mutation assays with bacteria (Salmonella typhimurium TM677) and a metabolically competent cell line derived from human B-lymphoblastoid cells (MCL-5) that contained activity for five cytochrome P450s and microsomal epoxide hydrolase found in human liver. Dibenzo[a,l]pyrene and benzo[a]pyrene, both potent animal carcinogens, were the most mutagenic substances in both assays. Dibenzo[a,l]pyrene was nearly 50-fold more potent than benzo[a]pyrene in human cells, but only 60% more mutagenic in Salmonella. The carcinogenic isomer dibenzo[a,h]pyrene, though nonmutagenic in bacteria, was active in human cells. The following mutagenic potency series, expressed as the minimum detectable mutagen concentration (MDMC) in nmol/mL, was obtained with Salmonella in the presence of rat liver postmitochondrial supernatant (PMS): dibenzo[a,l]pyrene (3.7), benzo[a]pyrene (5.8), dibenzo[a,e]pyrene (6.9), DB[ai]P (14.9), dibenzo[a,h]pyrene ( > 100). None of the compounds were mutagenic in the absence of postmitochondrial supernatant. In human MCL-5 cells the potency series was: dibenzo[a,l]pyrene (3.1 x

10-4), benzo[a]pyrene (1.5 x 10-2), dibenzo[a,e]pyrene (2.5 x 10-2), dibenzo[a,h]pyrene(0.5), dibenzo[a,i]pyrene (3.2). The human cell assay thus exhibited over a 10,000-fold range between the most mutagenic and least mutagenic compound, whereas in the bacterial assay there was only a corresponding four-fold difference if the nonmutagenic dibenzo[a,h]pyrene was excluded. The results were discussed in terms of their concordance with animal carcinogenicity studies.[Busby WF Jr et al; Mutat Res 342 (1-2): 9-16 (1995)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/7885398?dopt=Abstract" target=new>PubMed Abstract /GENOTOXICITY/ In cell transformation studies, 3,4-benzopyrene was slightly positive in the activated human WI-38 test and practically negative in the non-activated /assay/ ...[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 3364] **PEER REVIEWED** /GENOTOXICITY/ The metabolically competent human lymphoblastoid cell line MCL-5 was treated with a panel of mutagens to assess the induction of DNA damage. Treatment effects were observed by monitoring cell proliferation and by single-cell gel electrophoresis (SCGE). The direct-acting mutagens benzo[a]pyrene-7,8-diol 9,10-epoxide (BPDE) and 1-methyl-3-nitro-1-nitrosoguanidine (MNNG), as well as pro-mutagens requiring metabolic activation, i.e. benzo[a]pyrene (BaP), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 4-N-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and cigarette-smoke condensate (CSC), were assayed by SCGE. Assay schemes were adapted for the MCL-5 cell line and for low levels of strand break induction, by inclusion of the DNA synthesis inhibitors cytosine arabinoside and hydyroxyurea, and by extending the electrophoresis time. For all mutagens tested, dose-dependent increases of median and average tail moment values among 50 nucleoids per slide were observed. The determining factors for selecting the treatment doses for mutation-induction experiments were the solubility of BaP and PhIP in the exposure medium, and the cytotoxicity exhibited by BPDE, MNNG and CSC. Induction of DNA strand breaks was obtained at mutagen concentrations permitting sufficient cell proliferation, except in the case of MNNG.[Wolz L et al; Alternatives to laboratory animals : ATLA 30 (3): 331-339 (2002). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/12106012?dopt=Abstract" target=new>PubMed Abstract /GENOTOXICITY/ ... The characteristics of chromosomal aberrations induced in vitro by activated benzo[a]pyrene diol epoxide (BPDE) in lymphocyte cultures of 172 normal individuals ages 19-95 years /were described/ ... The BPDE-induced chromosomal aberrations were predominantly single chromatid breaks, with few isochromatid breaks or exchange figures. In the 172 normal subjects, the frequencies of both spontaneous and BPDE-induced chromatid breaks were not correlated with age, sex, ethnicity, or tobacco use. /Benzo[a]pyrene diol epoxide/[Wei Q et al; Cancer research 56 (17): 3975-3979 (1996). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/8752166?dopt=Abstract" target=new>PubMed Abstract /GENOTOXICITY/ A total of 67 polycyclic aromatic compounds that either have been identified (55) or are suspected to be present (12) in urban aerosol samples were tested for mutagenicity in a forward mutation assay based on human B-lymphoblastoid cells. The cell line used (designated

hlAlv2) constitutively expresses the cytochrome P4501A1, which is known to be necessary for the metabolism of many promutagens. The polycyclic aromatic compounds tested included 39 polycyclic aromatic hydrocarbons (PAH), 19 oxygen-containing polycyclic aromatic hydrocarbons (oxy-PAH) and nine NO2-substituted polycyclic aromatic hydrocarbons (nitro-PAH). A total of 26 polycyclic aromatic hydrocarbons were mutagenic. In comparing the minimum mutagenic concentrations of the mutagenic polycyclic aromatic hydrocarbons with that of benzo[a]pyrene (B[a]P) it was found that dibenzo[a,l]pyrene (DB[al]P), cyclopenta[c,d])pyrene (CPP), naphtho(2,1-a)pyrene, dibenzo[a,e]pyrene (DB(ae)P) and l-methylbenzo[a]pyrene were 24 +/ - 21, 6.9 +/ - 4.2, 3.2 +/ - 3.0, 2.9 +/ - 2.9 and 1.6 +/ - 1.4 times, respectively, more mutagenic than benzo[a]pyrene, and that dibenzo[a,k]fluoranthene and benzo[a]pyrene were approximately equally mutagenic. The 19 other mutagenic polycyclic aromatic hydrocarbons ... with the exception of 6H-benzo(c,d)pyren-6-one were over 50 times less active than benzo[a]pyrene...[Durant JL et al; Mutation Research 371 (3-4): 123-57 (1996)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/9008716?dopt=Abstract" target=new>PubMed Abstract /GENOTOXICITY/ ... Increasing exposures of human breast epithelial MCF10A cells to BaP at picomolar concentrations resulted in cellular transformation from a noncancerous stage to precancerous substages, in which cells acquired the cancerous abilities of a reduced dependence on growth factors, anchorage-independent growth, and disruption in acini formation on reconstituted basement membranes. Using cDNA microarrays, /the authors/ detected seven upregulated genes related to human cancers in BaP-transformed MCF10A cells. ...[Siriwardhana N et al; Molecular carcinogenesis 47 (5): 338-348 (2008). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/17932946?dopt=Abstract" target=new>PubMed Abstract /GENOTOXICITY/ /Investigators/ have recently found that transition metals such as nickel and chromium and oxidative stress induced lipid peroxidation metabolites such as aldehydes can greatly inhibit nucleotide excision repair (NER) and enhance carcinogen-induced mutations. Because PM is rich in metal and aldehyde content and can induce oxidative stress, /the authors/ tested the effect of PM on DNA repair capacity in cultured human lung cells using in vitro DNA repair synthesis and host cell reactivation assays. PM greatly inhibits NER for ultraviolet (UV) light and benzo[a]pyrene diol epoxide (BPDE) induced DNA damage in human lung cells. /The authors/ further demonstrated that PM exposure can significantly increase both spontaneous and UV-induced mutagenesis. These results together suggest that the carcinogenicity of PM may act through its combined effect on suppression of DNA repair and enhancement of DNA replication errors. /Benzo[a]pyrene diol epoxide/[Mehta, M et al; Mutation Research 657 (2): 116-121 (2008). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/18804180?dopt=Abstract" target=new>PubMed Abstract /GENOTOXICITY/ .../investigators/ assayed for levels of in vitro BPDE-induced DNA adducts and genotypes of single-nucleotide polymorphisms (SNPs) of the NER genes ERCC1 (rs3212986 and rs11615) and ERCC2/XPD (rs13181, rs1799793 and rs238406) in 707 healthy non-Hispanic whites. The linear trend test of increased adduct values in never to former to current smokers was statistically significant (P(trend) = 0.0107). The median DNA adduct levels for the ERCC2 rs1799793 GG, GA and AA genotypes were 23, 29 and 30, respectively (P(trend) = 0.057), but this trend was not observed

for other SNPs. After adjustment for covariates, adduct values larger than the median value were significantly associated with the genotypes ERCC1 rs3212986TT [odds ratio (OR) = 1.89, 95% confidence interval (CI) = 1.03-3.48] and ERCC2/XPD rs238406AA (OR = 0.64, 95% CI = 0.41-0.99) and rs238406CA (OR = 0.63, 95% CI = 0.45-0.89) compared with their corresponding wild-type homozygous genotypes. The results of haplotype analysis further suggested that haplotypes CAC and CGA of ERCC2/XPD, TC of ERCC1 and CACTC of ERCC2/XPD and ERCC1 were significantly associated with high levels of DNA adducts compared with their most common haplotypes. /These/ findings suggest that the genotypes and haplotypes of ERCC1 and ERCC2/XPD may have an effect on in vitro benzo[a]pyrene diol epoxide (BPDE)-induced DNA adduct levels./Benzo[a]pyrene diol epoxide/[Zhao, H et al; Carcinogenesis 29 (8): 1560-1566 (2008). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/18635523?dopt=Abstract" target=new>PubMed Abstract /GENOTOXICITY/ Polycyclic aromatic hydrocarbon-DNA adducts were evaluated in oral cells from 98 healthy volunteers by an immunohistochemical method using a specific antiserum against benzo[a]pyrene-DNA adducts revealed by the immunoperoxidase reaction. Mean adduct content, determined as relative staining intensity by absorbance image analyzer, was significantly higher in the cells from tobacco smokers compared with nonsmokers (330 +/- 98, n = 33 versus 286 +/- 83, n = 64, respectively) with a P = 0.013 obtained by two-sample t test with equal variances. ... In the smoker group, the PAH-DNA adduct content increases with the number of cigarettes. Thus, the relative staining intensity was 305 +/- 105 in the group smoking 1-10 cigarettes/day (n = 16), 347 +/- 77 in the 11-20 group (n = 14), and 386 +/- 112 in the group smoking more than 20 cigarettes/day (n = 3; P = 0.03 by nonparametric test for trend). No significant association was detected between PAH-DNA adducts in oral cells and variables such as residential area, oral infections, alcohol or vitamin intake, grilled food consumption, and professional activity. ...[Romano G et al; Cancer Epidemiology, Biomarkers &amp; Prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 8 (1): 91-96 (1999). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/9950245?dopt=Abstract" target=new>PubMed Abstract /GENOTOXICITY/ Despite numerous studies showing that mutagen sensitivity is a cancer predisposition factor, the heritability of mutagen sensitivity has not been clearly established. In this report, /investigators/ used a classic twin study design to examine the role of genetic and environmental factors on the mutagen sensitivity phenotype. Mutagen sensitivity was measured in peripheral blood lymphocytes from 460 individuals [148 pairs of monozygotic (MZ) twins, 57 pairs of dizygotic (DZ) twins, and 50 siblings]. The intraclass correlation coefficients were all significantly higher in MZ twins than in dizygotes (DZ pairs and MZ-sibling pairs combined) for sensitivity to four different mutagen challenges. Applying biometric genetic modeling, /the authors/ calculated a genetic heritability of 40.7%, 48.0%, 62.5%, and 58.8% for bleomycin, benzo[a]pyrene diol epoxide, gamma-radiation, and 4-nitroquinoline-1-oxide sensitivity, respectively. This study provides the strongest and most direct evidence that mutagen sensitivity is highly heritable, thereby validating the use of mutagen sensitivity as a cancer susceptibility factor.[Wu, X et al; Cancer research 66 (12): 5993-5996 (2006). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/16778168?dopt=Abstract" target=new>PubMed Abstract

/ALTERNATIVE and IN VITRO TESTS/ BaP metabolites have been shown to bind to DNA in cultured human hepatocytes, as well as in human bladder and tracheobronchial explants ... Human tissues are most active in metabolizing BaP, exhibiting at least a threefold higher covalent binding to DNA than hamsters, dogs, monkeys, or rats.[American Conference of Governmental Industrial Hygienists. Documentation of the TLV's and BEI's with Other World Wide Occupational Exposure Values. CD-ROM Cincinnati, OH 45240-1634 2007.] **PEER REVIEWED** /ALTERNATIVE and IN VITRO TESTS/ Human bronchial mucosa treated with benzo[a]pyrene in organ culture showed destruction of all cell types and distortion of columnar cell morphology but not of regenerative epithelium.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V32 216 (1983)] **PEER REVIEWED** /ALTERNATIVE and IN VITRO TESTS/ The effects of BaP on ... human fetal lung ... cultures have been observed to produce/ epithelial hyperplasia and inhibition of connective tissue growth.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V32 214 (1983)] **PEER REVIEWED** /ALTERNATIVE and IN VITRO TESTS/ Serum was taken from male human subjects (age 20-40 years) and the uptake /during in vitro incubation/ of (14)C-benzo[a]pyrene (BaP) and subsequent extraction of bound BaP was determined by radio-scintillation techniques. The initial uptake velocity for BaP by human (60 ug/mL x hr) was similar to that of rat serum for all concentrations of BaP used. Maximum uptake of BaP was estimated at 230 ug/mL for human serum. Gel filtration of human serum containing (14)C-BaP revealed that 80% was associated with low-density lipoproteins (LDL), 15% with high-density lipoproteins (HDL), and 5% with albumin. BaP binding at concentrations up to and including 50 ug BaP/mL was not saturable. In human serum the highest amount of bound BaP was associated with LDL (44-47%) and HDL (32-35%) components.[Aarstad K et al; Toxicology 47 (3): 235-45 (1987)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/3424381?dopt=Abstract" target=new>PubMed Abstract /ALTERNATIVE and IN VITRO TESTS/ Tthe effects of benzo[a]pyrene (BaP), 7,12-dimethylbenz(a)anthracene (DMBA), benzo[e]pyrene (BeP), and anthracene, as well as certain benzo[a]pyrene metabolites, on the levels of intracellular Ca(2+) and glutathione /were examined/ in human peripheral blood mononuclear cell. While benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene, benzo[e]pyrene, and anthracene did not cause a statistically significant decrease in GSH in human peripheral blood mononuclear cell at conc of 1 or 10 uM following a 6-, 48-, or 72-hr exposure, reactive benzo[a]pyrene metabolites including 4,5-epoxide benzo(a)pyrene and 7,8-diol-9,10-epoxide benzo(a)pyrene consistently produced a 20-30% depletion of glutathione in human peripheral blood mononuclear cell following a 6-hr treatment period. These benzo[a]pyrene metabolites also elevated intracellular Ca(2+) in human peripheral blood mononuclear cell during a 6-hr incubation. Results of these experiments suggest that metabolism of benzo[a]pyrene to certain epoxide metabolites lay be responsible for sulfhydryl damage leading to transient GSH depletion and Ca(2+) elevation. These results are consistent with the

hypothesis that sulfhydryl damage by certain PAH metabolites may lead to altered Ca(2+) homeostasis, leading to inhibition of cell activation and proliferation in human peripheral blood mononuclear cell.[Romero DL et al; Toxicol and Applied Pharmacol 144 (1): 62-9 (1997)] **PEER REVIEWED** /ALTERNATIVE and IN VITRO TESTS/ Cultures of human epidermal cells exhibit toxic response in presence of BaP, suggesting that cells possess microsomal aryl hydrolase system which is capable of converting the hydrocarbon into a toxic metabolite.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V3 114 (1973)] **PEER REVIEWED** /IMMUNOTOXICITY/ /Polycyclic aromatic hydrocarbons/ (PAHs) exert many important effects on the immune system of many species. The dose and route of exposure determine the nature of the effect of specific and adaptive immune responses. There are extremely limited or no data on many of the pure PAHs (with the exception of benzo[a]pyrene) and complex mixtures considered in this monograph. Studies with those PAHs that have been investigated indicate that the AhR plays a critical role in the activation of immunotoxic PAHs via diol-epoxide mechanisms that lead to DNA interactions, cause genotoxicity and suppress immunity by p53-dependent pathways. Benzo[a]pyrene diol epoxide may also affect protein targets and modulate lymphocyte signalling pathways via non-genotoxic (epigenetic) mechanisms. Certain PAH metabolites, such as benzo[a]pyrene quinones, may be formed via cytochrome P450-dependent and -independent (peroxidase) pathways, and redox-cycling PAH quinones may exert oxidative stress in lymphoid cells. Human exposures usually involve complex mixtures of PAHs, and it is difficult to attribute the relative contributions of individual PAHs to the overall immunotoxic effects. There is some evidence that human environmental exposures to PAHs may produce immunotoxicity, but further studies are needed.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Industrial Exposures, v 92 (2005). Summary available from, as of November 29, 2009: http://monographs.iarc.fr/ENG/Meetings/index1.php] **PEER REVIEWED** /OTHER TOXICITY INFORMATION/ Since PAHs are ubiquitous in the environment, and concomitant exposure of humans to PAHs and ultraviolet light (UV) is inevitable, the photomutagenicity and photocarcinogenicity of these compounds are of considerable importance to human health. PAH-contaminated skin may be exposed to sunlight, which is of greatest concern in outdoor workers who handle products that contain PAHs. Such workers include roofers, tanners and road construction workers. Some commercial medicines also contain PAHs. For example, coal tar, a complex mixture of PAHs, is widely used in creams, ointments, lotions and shampoos for the treatment of psoriasis (The Goeckerman therapy). A topical application of coal tar on the skin followed by irradiation with UV has been found to increase the risk for developing skin cancer.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Industrial Exposures, v 92 (2005). Summary available from, as of November 29, 2009: http://monographs.iarc.fr/ENG/Meetings/index1.php] **PEER REVIEWED** SKIN, EYE AND RESPIRATORY IRRITATIONS: BaP can cause exposure by inhalation and passing through the unbroken skin. Can cause skin irritation with rash and/or burning sensations. Exposure to sunlight can increase these effects. Eye contact can cause irritations and burns.[Sittig, M. Handbook of Toxic and Hazardous

Chemicals and Carcinogens, 2002. 4th ed.Vol 1 A-H Norwich, NY: Noyes Publications, 2002., p. 326] **PEER REVIEWED** MEDICAL SURVEILLANCE: Recommended medical surveillance: The following medical procedures should be made available to each employee who is exposed to coal tar pitch volatiles at potentially hazardous levels: Initial Medical Examination: A complete history and physical examination: The purpose is to detect existing conditions that might place the exposed employee at increased risk, and to establish a baseline for future health monitoring. Examination of the oral cavity, respiratory tract, bladder, and kidneys should be stressed. The skin should be examined for evidence of chronic disorders, for premalignant and malignant lesions, and evidence of hyperpigmentation or photosensitivity. /Coal tar pitch volatiles/[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 1] **PEER REVIEWED** Initial Medical Examination: Urinalysis: Coal tar pitch volatiles are associated with an excess of kidney and bladder cancer. A urinalysis should be obtained to include at a minimum: specific gravity, albumin, glucose, and a microscopic /examination/ on centrifuged sediment, as well as a test for red blood cells. /Coal tar pitch volatiles/[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 1] **PEER REVIEWED** Initial Medical Examination: Urinary cytology: Coal tar pitch volatiles are associated with an excess of kidney and bladder cancer. Employees having 5 or more years of exposure or who are 45 years of age or older should have a urinary cytology examination. /Coal tar pitch volatiles/[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 1] **PEER REVIEWED** Initial Medical Examination: Sputum cytology: Coal tar pitch volatiles are associated with an excess of lung cancer. Employees having 10 or more years of exposure or who are 45 years of age or older should have a sputum cytology examination. /Coal tar pitch volatiles/[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 1] **PEER REVIEWED** Initial Medical Examination: 14" x 17" chest roentgenogram: Coal tar pitch volatiles are associated with an excess of lung cancer. Surveillance of the lungs is indicated. /Coal tar pitch volatiles/[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 1] **PEER REVIEWED** Initial Medical Examination: Functional vital capacity and Forced expiratory volume (1 sec): Coal tar pitch volatiles are reported to cause an excess of bronchitis. Periodic surveillance is indicated. /Coal tar pitch volatiles/[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards.

DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 1] **PEER REVIEWED** Initial Medical Examination: A complete blood count: Due to the possibility of benzene exposure associated with coal tar pitch volatiles, a complete blood count is considered necessary to search for leukemia and aplastic anemia. /Coal tar pitch volatiles/[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 1] **PEER REVIEWED** Initial Medical Examination: Skin disease: Coal tar pitch volatiles are defatting agents and can cause dermatitis on prolonged exposure. Persons with pre-existing skin disorders may be more susceptible to the effects of these agents. /Coal tar pitch volatiles/[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 1] **PEER REVIEWED** Periodic Medical Examination: The aforementioned medical examinations should be repeated on an annual basis, and semi-annually for employees 45 years of age or older or with 10 or more years' exposure to coal tar pitch volatiles. /Coal tar pitch volatiles/[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 1] **PEER REVIEWED** PRECAUTIONS FOR "CARCINOGENS": ... in relation specifically to cancer hazards, there are at present no health monitoring methods that may ensure the early detection of preneoplastic lesions or lesions which may prelude them. Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning additional tests that might become useful or manditory. /Chemical Carcinogens/[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979., p. 23] **PEER REVIEWED** Antibodies to an epitope(s) on BPDE-DNA were found in the sera of approximately one-third of the workers. Detection of DNA adducts and antibodies to these adducts are internal indicators of exposure to benzo(a)pyrene.[Haugen A et al; Cancer Res 46 (8): 4178-83 (1986)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/3731085?dopt=Abstract" target=new>PubMed Abstract POPULATIONS AT SPECIAL RISK: /Polycyclic aromatic hydrocarbons/ (PAHs) must be metabolically activated in order to induce tumors. However, individuals differ in their ability to metabolize PAHs: those who are deficient in particular enzymes that activate PAHs to reactive metabolites may be at a lower risk for chemical carcinogenesis, whereas deficiencies in enzymes that detoxify reactive metabolites may increase this risk. Some of the epidemiological studies that have been conducted to date have shown positive relationships between genetic polymorphisms of drug-metabolizing enzymes and susceptibility to cancer, while others have been inconclusive. Many factors, including race,

age, sex, tobacco smoking, alcohol intake and genetic factors, could induce or inhibit drug-metabolizing activities which indicates that a complex interaction exists. Multi-gene and exposure interactions may also play a complex role in interpreting any increases in risk.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Industrial Exposures, v 92 (2005). Summary available from, as of November 29, 2009: http://monographs.iarc.fr/ENG/Meetings/index1.php] **PEER REVIEWED** PROBABLE ROUTES OF HUMAN EXPOSURE: ... Finished waters from various treatment sites are transported to consumers through a variety of pipelines. PAH's /polynuclear aromatic hydrocarbons/ leach from the tar or asphalt linings of these pipes ... resulting in increased concn of these cmpd in water reaching the consumers. ... Cement-lined pipes produce lower PAH concn, possibly because PAH's are adsorbed from water.[National Research Council. Drinking Water &amp; Health, Volume 4. Washington, DC: National Academy Press, 1981., p. 256] **PEER REVIEWED** IN GAS WORKS RETORT HOUSES MEAN CONCN RANGING FROM 1.4-4.8 MG/1000 CU M &amp; MAXIMUM CONCN OF 2300 MG/1000 CU M HAVE BEEN MEASURED ... 0.4 MG/1000 CU M /FOUND/ IN AIR POLLUTED BY COAL TAR PITCH FUMES, UP TO 2700 MG/1000 CU M IN INDUST EFFLUENTS &amp; 1000 MG/1000 CU M IN DOMESTIC COAL COMBUSTION STACK EFFLUENTS.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V3: 97 (1973)] **PEER REVIEWED** Influence of occupational ... factors upon benzo(a)pyrene exposure: Coke oven workers: Top side workers: 180 ug/day, side and bench exposure. 70 ug/day; Coal tar pitch worker: 750 ug/day; Airplane pilots: Transatlantic flights: 0.93 ug/day, domestic cross country: 1.38 ug/day; Employee in restraunt: 0.8 ug/day; Person living near expressway 24 hr/day (adverse meterology). 0.02 ug/day; Commuter on an expressway 2 hr/day (adverse meterology): 0.04 ug/day.[USEPA; Health Assessment Document for Polycyclic Organic Matter p.5-2 (1979) EPA-600/9-79-008] **PEER REVIEWED** Occupational situations involving heating organic materials may potentially result in exposure to this compound through inhalation of particulates or dermal contact with combustion products(1). Monitoring data indicate that the general population may be exposed to benzo(a)pyrene via smoking of tobacco, inhalation of polluted air, ingestion of food and drinking water contaminated by combustion effluents(2), and by cooking processes that produce smoke(SRC).[(1) Wallingford KM, Quehee SS; Polynuclear Aromatic Hydrocarbons: Mechanism, Methods, Metabolism. Cooke M, Dennis AJ, eds, Battelle Press (1985) (2) IARC; Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Polynuclear Aromatic Hydrocarbons Part I Chem and Environ Data 32: 211-24 (1983)] **PEER REVIEWED** Prior to renovations, coke oven workers wearing personal sampling pumps for a 6-8 hour shift were exposed to benzo(a)pyrene air concns ranging from, ug/cu m (workplace): 1.5 to 37 (battery top); 1.1 to 3.9 (coal conveyer); 1.7 to 12 (charging car); and 0.9 to 22 (oven doors); after renovation, exposure concns ranged from, ug/cu m (workplace): 0.2 to 6.8 (battery top); 0.1 to 1.7 (coal conveyer); and 0.2 to 0.3 (diverse)(1). Benzo(a)pyrene air concns for pot-room workers, detected using personal

sampling pumps for 6-8 hours in a Soderberg aluminum plant were as follows, ug/cu m (workplace): 2.3 to 36 (pot-anode); 1.7 to 2.1 (cathode); and 2.8 to 4.4 (crane)(1). Benzo(a)pyrene concns in air of non-smoking road pavers and construction workers, detected using personal sampling pumps for 6-8 hours, was < 0.05 ug/cu m(1). In surveys using both area and personal samplers at 8 aluminum reduction plants, and at 21 coke production facilities in the U.S. and Europe, occupational exposure to benzo(a)pyrene ranged from 0.01-975 ug/cu m and 0.01-161 ug/cu m, respectively(2); Occupational exposure at 14 roofing sites, four roofing shingle manufacturing plants and eight petroleum refineries in the U.S. ranged from < 0.03-27, < 0.02-3.4, and < 0.01-9.3 ug/cu m, respectively(2). Benzo(a)pyrene was detected at the following worksites, ug/cu m: coal liquefaction, 0.01 to 19; coal gas works, 1.4 to 4.8 ug/cu m; hot forging, 1.6 to 2.9; tire manufacturing, 0.002 to 0.032; steel mill, 0.04 to 4.2; and carbon impregnation process, 0.80 to 84(2). In a rubber footwear plant in Moscow, time-weighted average benzo(a)pyrene concns in the breathing zone of workers was, ug/cu m: 0.022 for handling, weighing and mixing of raw materials; 0.026 for milling and extruding; 0.04 for assembly and building; 0.26 for curing or vulcanizing; 0.14 for inspection and finishing, and 0.020 for footwear casting(3). Benzo(a)pyrene air concns in the impregnation and handling of treated wood was < 0.03 ug/cu m, except in manual metal-arc welding and in the boring of railroad ties, where it was 0.24 to 0.89 ug/cu m(4). In a Norwegian aluminum plant, the median level of benzo(a)pyrene in personal air samples was 4.1 ug/cu m(5). Fifteen truck drivers from Geneva, Switzerland were exposed to mean benzo(a)pyrene concns of 3.45 and 0.77 ng/cu m for local and long-distance drivers, respectively, who were nonsmokers and 2.50 and 1.47 for local and long-distance drivers, respectively who were smokers; sampling pumps were placed beside the driver in the truck cabin(6).[(1) Levin JO et al; Sci Total Environ 163: 169-77 (1995) (2) Wallingford KM, Quehee SS; Polynuclear Aromatic Hydrocarbons: Mechanism, Methods, Metabolism. Cooke M, Dennis AJ, eds, Battelle Press (1985) (3) Solionova LG et al; Scand J Work Environ Health 18: 120-3 (1992) (4) Heikkila PR et al; Scand J Work Environ Health 13: 431-7 (1987) (5) Haugen A et al; Med Lav 83: 506-10 (1992) (6) Guillemin MP et al; Int Arch Occup Environ Health 63: 439-47 (1992)] **PEER REVIEWED** Emissions generated during the pouring, cooling, and shakeout of castings made with the evaporative pattern casting process contained benzo(a)pyrene at concns of 61 and 11 ug/kg for aluminum and iron castings, respectively(1). Stationary air samples collected near the ovens of two silicon carbide process plants contained benzo(a)pyrene concns ranging from 19 to 309 ng/cu m in one plant and 23 to 93 ng/cu m in the second plant(2). Benzo(a)pyrene was detected in air samples (taken at breathing height using personal sampling pumps) collected in the furnace area of two silicon carbide process plants at concns (ng/cu m) ranging from (Plant A and B): 17 to 103 and 39 to 79 for the foreman; 4 to 35 and 31 to 247 for the crane operator; 56 to 98 and 42 to 52 for oven workers whose tasks were in close proximity to the oven; and 9 to 43 and 385 to 632 for oven workers whose tasks did not involve direct work at the oven site(2). Benzo(a)pyrene was detected in air samples (taken at breathing height using personal sampling pumps) of 6 workers in a plant producing carbon anodes for aluminum electrolysis, worksite - concn of benzo(a)pyrene (ug/cu m): forming section - 0.89 to 3.12; paste plant - 1.37 to 4.43; store section (broken green anodes and burned anodes) - 0.16 to 0.79; forming section - 2.12 to 4.88; store section (coke) paste plant - 0.17 to 2.03; and all worksites - 0.27 to 3.66(3). Benzo(a)pyrene has been detected in occupational environments at the following airborne concns (geometric mean), ug/cu m: coke plant, 8.02; carbon anode plant, 1.155; graphite plant, 0.083; silicon carbide plant, 0.036; metal recycling

plant, 0.014; and a bitumen paving plant, 0.010(4). Air sampled from the breathing zone of chimney sweeps during dirty work contained benzo(a)pyrene at concns ranging from 0.36 to 0.82 ug/cu m(5). Personal air samples collected at a new Finnish coking plant between 1988 and 1990 contained BaP concns of 1.4-2.5 ug/cu m (the highest mean concns were found among gas workers, at 6.0-10.3 ug/cu m); stationary air samples detected BaP at concns from < 0.01 to 31.15 ug/cu m(6). Air samples collected above the doors of smoking kilns used in Danish smokehouses contained benzo(a)pyrene in the particulate phase at a maximum concn of 78 ug/cu m(7).[(1) Gressel MG et al; Appl Ind Hyg 3: 11-17 (1988) (2) Petry T et al; Ann Occup Hyg 38: 741-52 (1994) (3) Petry T et al; Ann Occup Hygiene 40: 345-57 (1996) (4) Petry T et al; Chemosphere 32: 639-48 (1996) (5) Knecht U et al; Br J Ind Med 46: 47982 (1989) (6) Yrjanheikki E et al; Am Ind Hyg Assoc J 56: 782-7 (1995) (7) Nordholm L et al; Scand J Work Environ Health 12: 614-18 (1986)] **PEER REVIEWED** The benzo(a)pyrene concn generated from heating 100 g cooking oil to 270 deg C by a controlled electronic heater in a Chinese laboratory chamber is (ug/cu m): 0.22 for soybean oil, 0.12 for peanut oil, 0.06 for sunflower oil, 0.07 for lard oil, 0.11 for corn oil, 0.28 for mustard oil, and 0.41 for edible mixture oil(1). The concns of benzo(a)pyrene from 1 g tobacco (generated in a chamber by a smoking machine with a 2 second puff duration, 20 mL puff volume, and 1 puff per minute) in the following Chinese brands of cigarettes were (ug/cu m), 0.13 in Honghe, 0.01 in Hengda, 0.02 in Xili, 0.07 in Jinqiao, 0.09 in Zhongnanhai, 0.10 in Blackgold, and 0.18 in Greatwall(1).[(1) Zhang L et al; Chemosphere 75: 453-61 (2009)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/19200570?dopt=Abstract" target=new>PubMed Abstract Benzo(a)pyrene was detected in 35 urban (from London and Birmingham) and 39 suburban air samples collected for 24 consecutive hours by non-smoking volunteers wearing air sampling pumps, at total arithmetic mean (range) concns of 0.19 (not detected to 1.19), and 0.16 (not detected to 0.80) ng/cu m, respectively(1). Benzo(a)pyrene was detected in 17 rural air samples collected from Wales and West Midlands, UK, by non-smoking volunteers wearing air sampling pumps for 24 consecutive hours, at arithmetic mean (range) concns of 0.79 (0.02-5.36), and 0.15 (0.01-0.37) ng/cu m, respectively(1).[(1) Saborit JMD et al; Environ Sci Technol 43: 4582-8 (2009)] **PEER REVIEWED** BODY BURDEN: Milk of nursing mothers was analyzed for the presence of benzo(a)pyrene. Levels of 7.6 to 387 ng/mL (with the mean value of 129.5 ng/mL) were found in sample of ten nursing mothers. Blood samples taken from 56 children (aged 2-12 years) in and near Lucknow, India in September 2005 to August 2006, contained benzo(a)pyrene at a median concn of 1.4 ppb(2).[(1) Health &amp; Welfare Canada; Polycyclic Aromatic Hydrocarbons p.38 (1979) Report No. 80-EHD-50 (2) Singh VK et al; Arch Environ Contam Toxicol 54: 348-54 (2008)] **PEER REVIEWED** AVERAGE DAILY INTAKE: Benzo(a)pyrene air intake: 0.010 to 0.044 ug/day(1); (assume avg conc of 0.9 ng/cu m)(2) 0.18 ng; BaP water intake: 0.001 ug/day; benzo(a)pyrene food intake: 0.16 to 1.6 ug/day(1); (assume avg concn of 0.15 ug/kg)(2) 0.24 ug(SRC). The report of Czech Statistical Office, 2003, estimated the dietary daily intake of benzo(a)pyrene via fruits and vegetables in the Czech Republic (ng/day) are: apple, 2.3; apricot, 0.5; cauliflower, 0.4; cabbage, 0.1; cucumber, 0.5; grape, 0.8; parsley, 0.1; and tomato, 1.0(3).[(1) Vaessen HAMG et al; Toxicol Environ Chem 16: 281-94 (1988) (2)

Menzie CA et al; Environ Sci Technol 26(7): 1278-84 (1992) (3) Janska M et al; Bull Environ Contam Toxicol 77: 492-9 (2006)] **PEER REVIEWED** EMERGENCY MEDICAL TREATMENT: EMERGENCY MEDICAL TREATMENT: EMT COPYRIGHT DISCLAIMER: Portions of the POISINDEX(R) and MEDITEXT(R) database have been provided here for general reference. THE COMPLETE POISINDEX(R) DATABASE OR MEDITEXT(R) DATABASE SHOULD BE CONSULTED FOR ASSISTANCE IN THE DIAGNOSIS OR TREATMENT OF SPECIFIC CASES. The use of the POISINDEX(R) and MEDITEXT(R) databases is at your sole risk. The POISINDEX(R) and MEDITEXT(R) databases are provided "AS IS" and "as available" for use, without warranties of any kind, either expressed or implied. Micromedex makes no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the POISINDEX(R) and MEDITEXT(R) databases. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Micromedex does not assume any responsibility or risk for your use of the POISINDEX(R) or MEDITEXT(R) databases. Copyright 1974-2012 Thomson MICROMEDEX. All Rights Reserved. Any duplication, replication, "downloading," sale, redistribution or other use for commercial purposes is a violation of Micromedex' rights and is strictly prohibited.<p>The following Overview, *** POLYNUCLEAR AROMATIC HYDROCARBONS ***, is relevant for this HSDB record chemical. LIFE SUPPORT: o This overview assumes that basic life support measures have been instituted. CLINICAL EFFECTS: 0.2.1 SUMMARY OF EXPOSURE 0.2.1.1 ACUTE EXPOSURE A) In general, PAHs have a low order of acute toxicity in humans. B) PAHs and other compounds found in COAL TAR can produce a variety of non-cancer effects with chronic exposure. Chronic effects include: 1) EYES - Photosensitivity and irritation. 2) RESPIRATORY - Irritation with cough and bronchitis. 3) MOUTH - Leukoplakia. 4) DERMAL - "Coal tar warts" (precancerous lesions enhanced by UV light exposure), erythema, dermal burns, photosensitivity, acneiform lesions, irritation. 5) HEPATIC/RENAL - Mild hepatotoxicity or mild nephrotoxicity (animals). 6) GENITOURINARY - Hematuria. C) CANCER is the most significant PAH toxicity endpoint. 1) Increased incidences of cancers of the skin, bladder, lung and gastrointestinal tract have been described in PAH-exposed workers. 0.2.6 RESPIRATORY 0.2.6.1 ACUTE EXPOSURE A) Irritation, chronic cough, bronchitis, and bronchogenic cancer can occur with chronic exposure. 0.2.8 GASTROINTESTINAL 0.2.8.1 ACUTE EXPOSURE A) Leukoplakia and cancers of the lip and oral cavity can develop with chronic exposure.

0.2.9 HEPATIC 0.2.9.1 ACUTE EXPOSURE A) Mild hepatotoxicity has been reported in PAH-exposed rats. 0.2.10 GENITOURINARY 0.2.10.1 ACUTE EXPOSURE A) Hematuria, kidney and bladder cancer are possible effects of chronic exposure. Mild nephrotoxicity has been documented in PAH-exposed rats. 0.2.13 HEMATOLOGIC 0.2.13.1 ACUTE EXPOSURE A) Agranulocytosis, anemia, leukopenia, and pancytopenia developed in rats chronically fed PAHs. 0.2.14 DERMATOLOGIC 0.2.14.1 ACUTE EXPOSURE A) PRECANCEROUS LESIONS - "Coal tar warts" (precancerous lesions enhanced by UV light exposure), erythema, dermal burns, acneiform lesions, photosensitization and cancer may develop following chronic exposure. 0.2.19 IMMUNOLOGIC 0.2.19.1 ACUTE EXPOSURE A) An effect of PAHs on immune function might aid in the development of neoplasms. A number of PAH compounds are immunotoxic, and some suppress selective components of the immune system. 0.2.20 REPRODUCTIVE HAZARDS A) In experimental animal studies, PAHs and metabolites cross the placenta. Female offspring of experimental animals exposed to PAHs during pregnancy have a decrease in the number of functional oocytes, sometimes such that they are infertile. B) PAHs are lipophilic and are excreted in breast milk, allowing for secondary exposure of nursing infants, although the potential significance of such exposure has not been determined. 0.2.21 CARCINOGENICITY 0.2.21.2 HUMAN OVERVIEW A) Cancer is the most significant PAH toxicity endpoint. Some, but not all, PAHs are carcinogens. Certain PAH parent compounds are weak carcinogens, only becoming potent carcinogens after undergoing metabolism. Chronic or repeated exposure increases the likelihood of cancer initiation, as well as the potential for metabolism of a PAH procarcinogen to a carcinogen. B) Increased incidences of skin, bladder, lung, and possibly gastrointestinal tract cancers have been described in PAH-exposed workers, particularly associated with coal carbonization, coal gasification, and coke oven work. 0.2.21.3 ANIMAL OVERVIEW A) Lung tumors were induced in female mice from inhalation of exhausts containing PAHs (Schulte et al, 1994). 0.2.22 GENOTOXICITY A) CYTOGENETIC MARKERS OF HUMAN PAH EXPOSURE - Cells containing high frequencies of chromosomal aberrations were a sensitive marker for exposure to PAHs in coke oven and graphic electrode plant workers, compared with unexposed controls. There was no relation between cytogenetic findings and levels of benzo(a)pyrene-hemoglobin adducts (Buchet et al, 1995).

1) Arylamines derived from carcinogenic PAHs are mutagenically activated through S9-mediated metabolism of the related amine (Fu et al, 1982). 2) Nitro-PAH derivatives are potent bacterial mutagens. The mutagenic activity is dependent on enzymatic reduction of the nitro group and may require oxidative metabolism (Grosovsky et al, 1999; Rosenkranz &amp; Mermelstein, 1985). 3) In cultured human cells, benzo(a)pyrene and 7,12-demethylbenz(a)anthracene only caused a significant increase in T6 guanine-resistant mutations in the presence of cultured rat hepatocytes (Tong et al, 1981). 4) Nitrated PAHs have caused dose-dependent cell transformations in Syrian hamster embryo cells (DiPaolo et al, 1983). Metabolic reduction of the nitro- group on PAHs may be involved in their mutagenic effects. 5) Persons with a high degree of inducibility of the enzyme, aryl hydrocarbon hydroxylase, may be a high-risk population (ATSDR, 1993). B) A cross-sectional study evaluated the potential for exposure to PAHs to induce oxidative DNA damage in coke-oven workers (n=119), employed at an iron-steel factory. This study could not find clear evidence that PAH exposure induces oxidative DNA damage (Zhang et al, 2003). C) MUTAGENIC INTERMEDIATES 1) The PAH metabolic intermediates, diol-epoxides, are presumably mutagenic and can react to form DNA adducts, which may affect normal cellular replication (ATSDR, 1993; Ellenhorn &amp; Barceloux, 1988; Pike, 1992; Amin et al, 1993; Ronai et al, 1994). D) LACK OF EFFECT 1) Amongst a small group of Swedish road pavers exposed to asphalt fumes, there were no significant increases in sister chromatic exchanges or micronuclei in peripheral blood/lymphocytes as compared to unexposed controls (Jarvholm et al, 1999). LABORATORY: A) PAHs have been determined in the blood and tissues of experimental animals. Direct biologic measurement of PAHs currently is not clinically useful or cost-effective. Indirect methods of determining exposure are available but have not yet proven clinically useful (ATSDR, 1990). B) Acute respiratory effects in persons at PAH-containing workplaces are typically due to other toxic agents at the worksite (ATSDR, 1990). Arterial blood gases, chest x-ray, and other monitoring may be indicated, based on the patient's presentation and the exposure characteristics. C) Chronic effects, particularly cancer, are more common than acute toxicity. Routine monitoring and physical assessments (e.g, complete blood count, hepatic and renal function tests, chest xray and pulmonary function tests, dermal assessments) of individuals with significant exposure is recommended, even in the absence of symptoms (ATSDR, 1990). TREATMENT OVERVIEW: 0.4.2 ORAL EXPOSURE A) Toxicity from these substances involves chronic

exposure, toxicity after acute ingestions is unlikely and gastric decontamination is generally NOT indicated. 0.4.3 INHALATION EXPOSURE A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with inhaled beta2 agonist and oral or parenteral corticosteroids. B) Inhalational exposure to PAHs may be complicated by exposure to other substances which produce acute respiratory and systemic effects. Treat according to clinical presentation and exposure history. 1) If bronchospasm and wheezing occur, consider treatment with inhaled sympathomimetic agents. 2) Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary. 3) Monitor arterial blood gases and/or pulse oximetry, pulmonary function tests, and chest x-ray in patients with significant exposure. 0.4.4 EYE EXPOSURE A) DECONTAMINATION: Irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist, the patient should be seen in a health care facility. 0.4.5 DERMAL EXPOSURE A) OVERVIEW 1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water. A physician may need to examine the area if irritation or pain persists. 2) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines. 3) Some chemicals can produce systemic poisoning by absorption through intact skin. Carefully observe patients with dermal exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary. RANGE OF TOXICITY: A) The minimum lethal human dose to this agent has not been delineated. B) The maximum tolerated human exposure to this agent has not been delineated. ANTIDOTE AND EMERGENCY TREATMENT: Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand-valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Aromatic hydrocarbons and related compounds/[Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 209] **PEER REVIEWED**

Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. Administer activated charcoal ... . /Aromatic hydrocarbons and related compounds/[Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 209-10] **PEER REVIEWED** Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Consider drug therapy for pulmonary edema ... . Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias if necessary ... Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... .Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Aromatic hydrocarbons and related compounds/[Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 210] **PEER REVIEWED** ANIMAL TOXICITY STUDIES: EVIDENCE FOR CARCINOGENICITY: CLASSIFICATION: B2; probable human carcinogen. BASIS FOR CLASSIFICATION: Human data specifically linking benzo(a)pyrene (BAP) to a carcinogenic effect are lacking. There are, however, multiple animal studies in many species demonstrating BAP to be carcinogenic following administration by numerous routes. BAP has produced positive results in numerous genotoxicity assays. NOTE: At the June, 1992 CRAVE Work Group meeting, a revised risk estimate for benzo(a)pyrene was verified. ... The Carcinogenicity Background Document provides details on the rationale and methods used to derive the carcinogenicity values found in IRIS. ... HUMAN CARCINOGENICITY DATA: Inadequate. ANIMAL CARCINOGENICITY DATA: Sufficient. /Based on former classification system/[U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS) on Benzo(a)pyrene (BaP) (50-32-8) Available from, as of March 15, 2000. http://www.epa.gov/iris/] **PEER REVIEWED** A2; Suspected human carcinogen.[American Conference of Governmental Industrial Hygienists. Threshold Limit Values of Chemical Substances and Biological Exposure Indices, ACGIH, Cincinnati, OH 2009, p. 13] **PEER REVIEWED** There is sufficient evidence in experimental animals for the

carcinogenicity of benzo[a]pyrene. Benzo[a]pyrene is carcinogenic to humans (Group 1).[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Industrial Exposures, v 92 (2005). Summary available from, as of November 29, 2009: http://monographs.iarc.fr/ENG/Meetings/index1.php] **PEER REVIEWED** No data are available in humans. Sufficient evidence of carcinogenicity in animals. OVERALL EVALUATION: Group 2A: The agent is probably carcinogenic to humans.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. S7 58 (1987)] **PEER REVIEWED** Benzo(a)pyrene: reasonably anticipated to be a human carcinogen. /Polycyclic Aromatic Hydrocarbons/[DHHS/National Toxicology Program; Eleventh Report on Carcinogens: Benzo(a)pyrene (50-32-8) (January 2005). Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s150pah.pdf] **QC REVIEWED** NON-HUMAN TOXICITY EXCERPTS: /LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ In order to investigate the relationship between aryl hydrocarbon hydroxylase (AHH) activity and exposure to benzo[a]pyrene [B(a)p] and fluoranthene (FLA), AHH activities in liver tissues of male and female F-344 rats were determined. Based on a range-finding study, doses of 0, 5, 50, and 100 mg/kg B(a)p or 0, 150, 750, and 1500 mg/kg FLA were administered in the animal diet over a 90-day period. After dosing, animals were sacrificed, liver tissues were removed, and microsomes were isolated. AHH activities were determined by reverse-phase HPLC coupled with fluorescence detection using 3-hydroxy B(a)p, and trans-2,3-dihydroxy-1,10-epoxy-1,2,3,10b tetrahydrofluoranthene as the standards. A dose-dependent increase in enzyme activity was observed with increased B(a)p or FLA exposure in both males and females. /The/ results also demonstrate that B(a)p-exposed females possess a higher AHH activity than males, but there is no significant sex difference with regard to enzyme activity in the case of FLA at higher doses. Overall, /these/ findings suggest that long-term exposure to the parent compound results in elevated levels of AHH activity, which may contribute to the formation of toxic reactive metabolites and subsequent symptoms in target organs.[Ramesh A et al; Journal of biochemical and molecular toxicology 14 (3): 155-161 (2000). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/10711631?dopt=Abstract" target=new>PubMed Abstract /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In several studies in which benzo[a]pyrene was applied to the skin of different strains of mice, benign and malignant skin tumors were observed. No skin tumors developed in mice that lacked the aryl hydrocarbon receptor (AhR-/mice). In a large number of initiation- promotion studies, benzo[a]pyrene was active as an initiator when applied to the skin of mice.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Industrial Exposures, v 92 (2005). Summary available from, as of November 29, 2009: http://monographs.iarc.fr/ENG/Meetings/index1.php] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In a series of studies in newborn and adult mice, intraperitoneal injection of

benzo[a]pyrene increased the incidences of liver and lung tumors and, occasionally, those of forestomach and lymphoreticular tumors.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Industrial Exposures, v 92 (2005). Summary available from, as of November 29, 2009: http://monographs.iarc.fr/ENG/Meetings/index1.php] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Subcutaneous injection of benzo[a]pyrene induced malignant tumors (mainly fibrosarcomas) at the injection site in mice, rats and hamsters. AhR-/mice did not develop tumors.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Industrial Exposures, v 92 (2005). Summary available from, as of November 29, 2009: http://monographs.iarc.fr/ENG/Meetings/index1.php] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Intratracheal administration of benzo[a]pyrene alone or mixed with particulates and suspended in saline with or without suspendents resulted in benign and malignant respiratory tumors in numerous studies in hamsters and in a few studies in rats and mice. Larger benzo[a]pyrene particles were generally more effective than smaller ones. Mice that lack the nucleotide excision repair gene XPA (XPA-/- mice) showed a stronger lung tumor response after intratracheal instillation of benzo[a]pyrene than their similarly treated XPA+/+ and XPA+/- counterparts.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Industrial Exposures, v 92 (2005). Summary available from, as of November 29, 2009: http://monographs.iarc.fr/ENG/Meetings/index1.php] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Following administration of benzo[a]pyrene by gavage or in the diet to mice and rats of different strains, increased tumor responses were found in several organs, including the lung, forestomach, liver, lymphoreticular tissue, esophagus and tongue. Oral administration of benzo[a]pyrene to XPA-/- mice resulted in a significantly higher increase of lymphoma than that observed in similarly treated XPA+/- and XPA+/+ mice. Benzo[a]pyrene administered by gavage to XPA-/-/p53+/- double transgenic mice induced tumors (mainly splenic lymphomas and forestomach tumors) much earlier and at higher incidences than in similarly treated single transgenic and wild-type counterparts. These cancer-prone XPA-/- or XPA-/-/p53+/- mice also developed a high incidence of (mainly) forestomach tumors when fed benzo[a]pyrene in the diet.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Industrial Exposures, v 92 (2005). Summary available from, as of November 29, 2009: http://monographs.iarc.fr/ENG/Meetings/index1.php] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Dose-related increases in the incidence of malignant lung tumors were found after injection of benzo[a]pyrene in beeswax/tricaprylin or beeswax/trioctanoin into the lung tissue of rats.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Industrial Exposures, v 92 (2005). Summary available from, as of November 29, 2009: http://monographs.iarc.fr/ENG/Meetings/index1.php] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In a lifespan inhalation study in male hamsters, benzo[a]pyrene induced dose-related

increases in the incidences of polyps, papillomas and squamous-cell carcinomas in both the upper respiratory tract (nose, larynx and trachea) and the upper digestive tract (pharynx, esophagus and forestomach).[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Industrial Exposures, v 92 (2005). Summary available from, as of November 29, 2009: http://monographs.iarc.fr/ENG/Meetings/index1.php] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Repeated application of benzo[a]pyrene to the buccal pouch mucosa of male hamsters resulted in a high incidence of forestomach papillomas.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Industrial Exposures, v 92 (2005). Summary available from, as of November 29, 2009: http://monographs.iarc.fr/ENG/Meetings/index1.php] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In rat subcutaneous tracheal grafts exposed to benzo[a]pyrene in beeswax, high incidences of squamous-cell carcinomas were found. In one of 13 benzo[a]pyrene-exposed human bronchial grafts transplanted subcutaneously into nude mice, a squamous-cell carcinoma developed, while four other grafts developed preneoplastic epithelial changes.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Industrial Exposures, v 92 (2005). Summary available from, as of November 29, 2009: http://monographs.iarc.fr/ENG/Meetings/index1.php] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In three studies in rats, benign and malignant mammary gland tumors developed after intramammillary administration of benzo[a]pyrene.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Industrial Exposures, v 92 (2005). Summary available from, as of November 29, 2009: http://monographs.iarc.fr/ENG/Meetings/index1.php] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In three studies in mice, intracolonic instillation of benzo[a]pyrene induced a variety of benign and malignant tumors in various organs but no colonic tumors.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Industrial Exposures, v 92 (2005). Summary available from, as of November 29, 2009: http://monographs.iarc.fr/ENG/Meetings/index1.php] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Repeated oral ingestion of benzo[a]pyrene caused hypoplastic anemia in mice; intratracheal instillation of 0.63 mg once weekly for life into Syrian hamsters resulted in the development of bronchogenic adenomas, growth of epithelial cords of cells into lung tissues, tumor formation, and changes to hyperplastic, then squamous metaplastic epithelium, and papillomas.[Bingham E et al; Patty's Toxicology CD-ROM (2005). NY, NY: John Wiley &amp; Sons; Polycyclic and Heterocyclic Aromatic Hydrocarbons. Online Posting Date: April 16, 2001.] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ No stomach tumors were found at end of 110-day treatment with diets containing up to

30 ppm benzo[a]pyrene. Tumor incidences lower than 10% were observed in mice receiving 40-45 ppm for 110 days, whereas mice bearing stomach tumors exceeded 70% among those given 50-250 ppm benzo[a]pyrene for 122-197 days.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V3 103 (1973)] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Single intragastric administration of 0.2 mg/mouse in polyethylene glycol produced total of 14 tumors /in forestomach/ in 5 /of 11/ animals ... Tumors appeared following single doses of 0.05 &amp; 0.012 mg/mouse in 0/9 &amp; 2/10 mice. Diet containing 250 ppm benzo(a)pyrene fed for different periods of time produced the following incidences of tumors of forestomach: 1 day of feeding, 0%; 2-4 days of feeding, 10%; 5-7 days of feeding, 30-40%; 30 days of feeding, 100%. In subsequent experiment, diet containing 250 ppm ... fed 140 days to mice of same strain starting at 18-30 days of age ... produced leukemias and lung adenomas in additionn to stomach tumors. The ability of benzo(a)pyrene to produce lung adenomas when administered in diet was confirmed in another study.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V3 102 (1973)] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Single oral administration of 100 mg benzo(a)pyrene to 50-day-old female Sprague-Dawley rats produced mammary tumors in 8 of 9 animals. In another study with Sprague-Dawley rats of both sexes aged 3.5 mo at the beginning of the experiment, daily doses of 2.5 mg benzo(a)pyrene per rat induced papillomas in esophagus and forestomach in three out of 40 animals.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V3 103 (1973)] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Bi-weekly administration of 2-5 mg benzo(a)pyrene in oil by stomach tube produced 5 papillomas of stomach in 67 hamsters treated for 1-5 months, 7 papillomas and 2 carcinomas in 18 treated for 6-9 months, and 5 papillomas in 8 treated for 10-11 months. In a subsequent experiment with 13 hamsters, a diet containing 500 ppm benzo(a)pyrene given for 4 days/wk for up to 14 months caused total of 12 tumors (2 in esophagus, 8 in forestomach, and 2 in intestine) in 8 hamsters.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V3 104 (1973)] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ ... Dose-response studies, including a no-effect dose level, ... indicate that the threshold dose is affected by the strain of mouse and the solvent chosen. Three weekly applications of benzo(a)pyrene in acetone to CAF1 mice induced no skin tumors at a concentration of 0.0005%, a total of 6 papillomas and 2 carcinomas among 19 mice at a concentration of 0.001%, and increasing incidence of benign and malignant tumors with progressively shorter latent periods at higher doses. In Swiss and C57BL mice, tumors were not induced at a concentration of 0.001% or less, whereas incidences approaching 100% were found at 0.005% or higher concentration.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to

Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V3 104 (1973)] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ ... /In dose-response study/ toluene was used as solvent &amp; SWR, C3HeB, and A/He mice were painted 3 times weekly with different amounts of Benzo(a)Pyrene. In SWR and C3HeB mice the lowest effective dose was 0.38 ug Benzo(a)Pyrene per application, with an obvious dose-response relationship above this dose for both percentage of tumor-bearing animals and the shortening of latent period; doses of 0.15 ug were ineffective. On the other hand, in A/He mice, paintings with 0.15 to 3.8 ug Benzo(a)Pyrene were ineffective, whereas tumors were induced following doses of 19 ug or more. With acetone as solvent &amp; using Swiss mice, borderline activity was detected following 3 times weekly painting with 0.1 to 1.0 ug Benzo(a)Pyrene, while tumors appeared with 3 ug and above.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V3 104 (1973)] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ ... Seven /skin/ papillomas and four carcinomas /were produced/ among 15 rats painted weekly with 0.5 to 1% solution of Benzo(a)Pyrene in benzene /in an experiment lasting 150 days./[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V3 106 (1973)] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Bi-weekly paintings with a 0.01% solution of Benzo(a)Pyrene in acetone for 40 days did not produce skin tumors among 10 Syrian golden hamsters. A total of 8 applications of 4 drops of 0.8% soln in mineral oil produced 1 melanoma among 25 survivors at 33 weeks.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V3 106 (1973)] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Twice-weekly painting with 0.3% solution of Benzo(a)Pyrene in benzene for 400 days produced 1 carcinoma and 10 papillomas among 10 rabbits. This result has been confirmed repeatedly ... Some evidence of dose-response relationship ... /comes/ from study on small groups of rabbits painted 5 times weekly with concentration of Benzo(a)Pyrene in acetone ranging between 0.0001% and 0.5%: tumors appeared following application of ... 0.005% or more. /SRP: Note: the vehicle, benezene, is also a carcinogen./[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V3 107 (1973)] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ ... One or 5 intratracheal administrations of 100 mg Benzo(a)Pyrene to 8 rats produced at least 3 lung tumors ... 10 monthly intratracheal injections of either 0.0005, 0.002, 0.01, 0.05, 0.25, or 2.5 mg Benzo(a)Pyrene mixed with blood substitute, BK-8, and India ink were ... /observed/ for 2 yr. No lung tumors were found at the 2 lowest concentrations ... At higher dosages percentages of animals developing lung tumors were, respectively, 14%,

28%, 43%, and 80% .[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V3 107 (1973)] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Several dose-response studies are available, some ... permit comparison with other carcinogens tested under same conditions in same lab ... On induction of local sarcomas following single injections of Benzo(a)Pyrene in tricaprylin, no tumors were found following doses of 0.031 mg or less, whereas 4 of 20 C3H mice developed tumors with 0.062 mg, higher tumor incidences ... following greater doses. The thresholds of carcinogenicity for 3-methylcholanthrene (MC) and dibenz(a,h)anthracene (DB(a,h)A) in the same experiment were, respectively, 0.0078 and 0.0019 mg ... Avg minimal latent periods were 3 months for Benzo(a)Pyrene, 2.5 months for MC, and 3.7 mo for DB(a,h)A.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V3 109 (1973)] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Induction of hepatomas and/or lung adenomas and occasional tumors at other sites in mice of different strains was recorded following admin of Benzo(a)Pyrene during first days of life at doses of 20-40 ug/mouse in different solvents.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V3 110 (1973)] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Weekly ip injections of 2 mg Benzo(a)Pyrene as colloidal suspension in water to 80 ST/A mice induced abdominal fibrosarcomas in 81% of 40 females and 73% of 40 males with average latent period of 33 wk.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V3 112 (1973)] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Single ip admin of 10 mg Benzo(a)Pyrene produced 2 mammary and 2 uterine carcinomas among 10 Wistar rats within 1 yr, whereas no mammary tumors were found in controls.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V3 112 (1973)] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ A dose of 39 mg/kg /Benzo(a)Pyrene/ in lipid emulsion given iv to 50-day-old female Sprague-Dawley rats induced mammary carcinomas in nine of 30 animals within 98 days.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V3 112 (1973)] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ At oral doses estimated to be between 6-12 mg/kg bw/day, leukemia developed 100 or more days later in nonresponsive AHD/AHD homozygous mouse but not in responsive

AHB/AHD heterozygote. An excess of dietary alpha-naphthoflavone (ANF) 20 times greater than the amount of Benzo(a)Pyrene prevented these hematopoietic neoplasms. ANF-sensitive metabolism of Benzo(a)Pyrene presumably cytochrome P1-450 - in the bone marrow of AHD/AHD individuals may be responsible for causing the leukemia.[Nebert DW, Jensen NM; Biochem Pharmacol 28 (1): 149-52 (1979)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/758905?dopt=Abstract" target=new>PubMed Abstract /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ To improve the Ames chemical carcinogen screening test, several species of animals, including rats, mice, guinea pigs, hamsters, and rabbits, were pretreated with polychlorinated biphenyl (PCB), 3-methylcholanthrene (3-MC) anc phenobarbital (PB) and tested for the effects of the increase of revertants colonies of Salmonella typhimurium TA98 and TA100. Among 12 strains of 5 mammalian species, S-9 fraction from PCB-treated Hartley guinea pigs proved more effective than that from PCB-treated SD rats in detecting 3 different types of mutagens which included Benzo(a)Pyrene.[Suzuki H et al; J Pestic Sci (Nihon Noyakugaku Kaishi) 2 (4): 421-6 (1977)] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ IP admin of 100-150 mg/kg bw Benzo(a)Pyrene to C3H/Anf mice in mid- or late pregnancy results in marked and persistent suppression of the immune system in the offspring. Application of Benzo(a)Pyrene to skin of pregnant mice (strain unspecified) over 4 generations resulted in sensitization of the offspring to the effects of Benzo(a)Pyrene, so that an increase in rate of appearance of papillomas and carcinomas was observed following skin application to offspring over that in control mice that had not been treated in utero.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V32 215 (1983)] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Three sc or ip injections to ICR/HA mice of 2-4 mg Benzo(a)Pyrene at 11th, 13th, and 15th day of pregnancy resulted in increased incidence of lung adenomas and initiation of skin carcinogenesis in offspring. Foster nursing did not alter these effects.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V3 113 (1973)] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Transplacental carcinogenesis has ... been shown in rabbits.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V32 215 (1983)] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Squamous cell carcinogens were tabulated in rats exposed to atmospheres of SO2 or benzo(a)pyrene alone, or to both in combination, 5 days per wk for their lifetime. No cancers were produced in 15 animals exposed to SO2 alone (10 ppm, 6 hr/day), and one cancer in 30 animals exposed to 10 mg/cu m of benzo(a)pyrene alone (1 hr a day). Exposure to SO2 (10 ppm, 6 hr/day) and then to an SO2 (4 ppm) + benzo(a)pyrene (10 mg/cu m) mixture for 1 hr a day produced 9 cancers in 46 rats.[European Commission, ESIS; IUCLID

Dataset, Sulfur dioxide (CAS #7446-09-5) p.62 (2000 CD-ROM edition). Available from, as of November 9, 2009: http://esis.jrc.ec.europa.eu/] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ ... Benzo(a)pyrene produced tumors in more primitive primates (bush babies and tree shrews), than in rodents.[Adamson RH, Sieber SM; Basic Life Sci 24 (Organ Species Specif Chem Carcinog): 129-56 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6860262?dopt=Abstract" target=new>PubMed Abstract /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ The tumorigenicity of benzo[a]pyrene applied topically as a skin tumor initiator in Sencar mice and the formation of epidermal Benzo(a)Pyrene/deoxyribonucleoside adducts were compared over a similar range of doses (50-1600 nmol). The tumor-initiating activity of Benzo(a)Pyrene, its covalent binding to mouse epidermal DNA, and the formation of the major hydrocarbon/deoxyribonucleoside adduct showed approx parallel dose-response curves. The half-life of the Benzo(a)Pyrene/deoxyribonucleoside adducts and the total radioactivity bound to the DNA were 4.5 and 5.5 days, respectively. However, in spite of the loss of measurable DNA-bound material, the tumor yield was unchanged regardless of whether promotion was begun 7 or 21 days after initiation. Thus, there was a possible causal relation between Benzo(a)Pyrene/deoxyribonucleoside adduct formation and papilloma formation in mouse skin.[Ashurst SW et al; Cancer Res 43 (3): 1024-9 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6297716?dopt=Abstract" target=new>PubMed Abstract /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Rats and mice were exposed /by inhalation/ to combustion gases of coal-burning furnace enriched with benzo[a]pyrene (50-90 ug/cu m) and other polycyclic aromatic hydrocarbons (PAH) 16 hr/day, 5 days/wk. After approx 22-mo exposure, the incidence of lung neoplasm was approx 10-fold above controls.[Heinrich U et al; Exp Pathol 29 (1): 29-34 (1986)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/3699126?dopt=Abstract" target=new>PubMed Abstract /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ ... Two experiments involving the repeated application of benzo[a]pyrene (BaP) to the dorsal skin of female Ha/ICR mice /are reported/. In the first experiment, the cytokinetic, inflammatory, and DNA adduct responses were studied daily over a 9-day period encompassing the fourth and fifth weekly applications of benzo[a]pyrene at doses of 16, 32, and 64 ug. The second experiment involved the same cytokinetic measurements at 1, 3, 5, and 8 mo, and the weekly benzo[a]pyrene doses were 4, 8, and 16 ug. The first study showed that after each application of 32 or 64 ug benzo[a]pyrene, there was a wave of slow DNA synthesis in the epidermis which peaked at 24 hr, in coincidence with a wave of benzo[a]pyrene-DNA adducts, followed by the appearance of dead and damaged keratinocytes. For the first few days after benzo[a]pyrene application there was a depression in the mitotic rate which recovered several days before the next benzo[a]pyrene application. There was a predominantly monocytic dermal inflammation throughout the observation period. In the second experiment, at the lower benzo[a]pyrene doses, there was proliferative depression at 1 mo, without dermal inflammation. With continued exposure, the proliferative depression changed to a dose-dependent increase in the rate of proliferation and dermal inflammation. The level of benzo[a]pyrene-DNA adducts was followed in the 4 ug/wk dose group, which showed a threefold increase after 4 mo

with the appearance of inflammation and heightened cell proliferation. These results suggest that the delayed inflammatory reaction, possibly based on a cell-mediated immune reaction to benzo[a]pyrene, might have been responsible for the late cytokinetic responses and the associated increase in the level of benzo[a]pyrene-DNA adducts.[Albert RE et al; Toxicol Appl Pharmacol 136 (1): 67-74 (1996)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/8560481?dopt=Abstract" target=new>PubMed Abstract /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ ...The DNA binding potencies of dibenzo(a,e)pyrene (DB(a,e)P), dibenzo(a,h)pyrene (DB(a,h)P), dibenzo(a,i)pyrene (DB(a,i)P), dibenzo(a,l)pyrene (DB(a,l)P) and benzo(a)pyrene (B(a)P), when applied topically, either singly or in combination, to the skin of male Parkes mice /was examined/. DNA isolated from the skin and lungs was analyzed by 32P-postlabelling. The adducts formed by each polycyclic aromatic hydrocarbon exhibited markedly different chromatographic mobilities on polyethyleneimine-cellulose TLC plates. The relative binding potencies of the compounds in both skin and lungs were: dibenzo(a,l)pyrene > dibenzo(a,i)pyrene > dibenzo(a,e)pyrene, in good agreement with their reported carcinogenicities in mouse skin. The majority of adducts were removed from DNA within 21 days of treatment, but low levels of adducts were found to persist for at least 3 months in both tissues. When dibenzo(a,l)pyrene, dibenzo(a,e)pyrene and benzo(a)pyrene were applied together to mouse skin, a total binding 31% lower than expected was detected, while with a mixture of dibenzo(a,e)pyrene and benzo(a)pyrene the binding to DNA in skin was 65% higher than expected from the binding levels of the carcinogenes when applied singly...[Hughes NC, Phillips DH; Carcinogenesis (EYNSHAM); 11 (9): 1611-20 (1990)] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ The experimental data on the effects of a widespread carcinogen, benzo[a]pyrene (BaP), on individual reactions of rats were treated using mathematical-statistical methods. The individual reactions were analyzed in dependence of doses and modes of administration (single or chronic). The analysis revealed a statistically significant correlation between life span and urinary content of (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (7,8-BaP) in rats treated with BaP. The calculated regression equations revealed that the individual sensitivity to carcinogen in case of the BaP single administration to rats is mainly determined by efficiency of excretion of the BaP active forms out of the organism, whereas after chronic BaP administration it is determined by mechanisms of enzymatic deactivation of BaP.[Sibirtsev VS; Biochemistry (Biokhimiya) 71 (1): 90-98 (2006). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/16457625?dopt=Abstract" target=new>PubMed Abstract /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In a four-generation mouse study, the incidence of papillomas and carcinomas increased.[Warshawsky D; Patty's Toxicology CD-ROM (2005). NY, NY: John Wiley &amp; Sons; Polycyclic and Heterocyclic Aromatic Hydrocarbons. Online Posting Date: April 16, 2001.] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/Transgene expression and skin tumorigenicity were investigated in transgenic TG-AC mice carrying the v-Ha-ras after treatment with benzo[a]pyrene (BP). Animals treated with 40 ug BP (x2/week/mouse) showed 100% tumor response after 25 weeks, as did 40% of the mice treated with 20 ug BP but 10 ug BP did not produce a tumor response. In the case of animals treated with 40 ug BP for 25 weeks, most of the tumors were proven to be carcinomas (80%,

4 out of 5 mice), and all tumors were shown to be positive in terms of transgene expression detected by in situ hybridization. These data suggest that BP was tumorigenic in a dose-dependent manner in TG-AC mice and that TG-AC mice were dependent on transgene expression during BP carcinogenesis.[Lee, BM; Biological &amp; Pharmaceutical Bulletin 26 (5): 733-735 (2003). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/12736523?dopt=Abstract" target=new>PubMed Abstract /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ .../The authors/ selected the p53 haploinsufficient Tg.AC (v-Ha-ras) mouse as a model, because it contains an activated, carcinogen-inducible ras oncogene and an inactivated p53 tumor suppressor gene, which are frequent genetic alterations in human cancers. These mice develop chemically induced benign and malignant skin tumors rapidly which can easily be quantified. Mice were fed basal diets with or without 3% N-acetyl-L-cysteine (NAC), a well-recognized antioxidant, prior to, during and after topical application of the carcinogen benzo[a]pyrene (64 microg/mouse) applied twice per week for 7 weeks. Tumor incidence exceeded 90% for both groups, and NAC did not reduce tumor latency. Mice fed NAC displayed a 43% reduction (P < 0.05) in tumor multiplicity and delayed the appearance of lesions (P < 0.05). Dietary NAC also significantly (P < 0.05) improved group survival by 5 weeks. Total tumor yields were reduced in both dietary groups but malignant spindle cell tumors (SCT) increased by 25% in NAC-fed mice. The v-Ha-ras oncogene and p53 protein products were clearly co-expressed in both benign and malignant lesions from both dietary groups. In summary, dietary supplementation with NAC was chemopreventive, but the marginal increase in SCT suggests a paradoxical effect.[Martin KR et al; Carcinogenesis 22 (9): 1373-1378 (2001). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/11532857?dopt=Abstract" target=new>PubMed Abstract /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ /Investigators/ designed a novel short-term bitransgenic model to better characterize the effects of benzo[a]pyrene (BP) exposure on multi-organ carcinogenesis and to evaluate the effects of a well-recognized antioxidant, N-acetyl-L-cysteine (NAC), on neoplasia. /The authors/ selected the p53 heterozygous Tg.AC (v-Ha-ras) mouse model for our studies because these mice possess a carcinogen-inducible ras oncogene and one functional p53 tumor suppressor allele. Both mutations occur frequently in human cancers. In a 2 x 2 experimental design, both female and male mice were fed basal diet alone or containing 3% NAC and administered by gavage corn oil vehicle alone or containing 20 mg BP/kg body weight given twice weekly for 10 weeks. Mice (n = 15 for each grouping and sex) were subsequently observed an additional 18 weeks followed by tissue collection for evaluation of multi-organ pathology. Benzo[a]pyrene increased neoplasia in the thymus, spleen, stomach, and hematopoietic system after 28 weeks. /Investigators/ observed modest NAC-associated decreases in BP-induced pathology of the liver, papilloma formation and hyperplasia in the forestomach, and the occurrence of malignant lymphoma. Benzo[a]pyrene exposure reduced survival to approximately 40% in male mice, suggesting toxicity; however, survival in control groups was approximately 60%. Survival decreased to approximately 30% for females in all groups. /The authors/ noted a clear, but nonsignificant, 15% decline in body weights of male, but not female, mice fed NAC, although food intake did not differ. Collectively, the data suggested carcinogen and antioxidant-associated effects on neoplasia that appeared sex-dependent.[Martin KR et al; Toxicol Sci 81 (2): 293-301 (2004). Available from, as of November 23, 2009:]

**PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/15254344?dopt=Abstract" target=new>PubMed Abstract /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ The Big Blue mouse was used to investigate the role of cell proliferation in mutation fixation in the mouse back skin model of carcinogenesis. Phorbol 12-myristate 13 acetate (TPA) was applied to the dorsum of Big Blue mice to manipulate cell proliferation, and benzo[a]pyrene (BaP) or BaP-diolepoxide (BPDE) was applied to produce premutagenic DNA damage. Mutations in the lacI transgene of skin DNA were measured. BaP and BPDE elevated mutant frequency, DNA adducts, and cell damage over untreated and acetone-treated mice. BPDE-DNA adducts peaked within 30 min of exposure and DNA adducts, formed after application of both BaP and BPDE, declined rapidly with time. As the dose of BaP increased (4 to 64 microg), DNA adducts, mutant frequency, and cell damage increased in a dose-dependent manner. TPA applied after BaP and BPDE further increased mutant frequency, DNA adducts, and cell damage, while variably affecting mitotic index and other measures of cell proliferation. TPA became less effective at increasing mitotic index as the dose of BaP increased, although all measures of cell proliferation, taken together, increased. The most effective production of DNA adducts and mutations occurred when the carcinogen was applied simultaneously with or within 1 hr of TPA. Mutations induced by BPDE were predominantly base substitutions: of these base substitutions, 35% were G:C -- > A:T transitions, and 36% were G:C -- > T:A and 29% G:C -- > C:G transversions. Approximately 88% of all mutations and 100% of base substitutions were at G:C sites; 60% of all mutations and 70% of the base substitution mutations occurred at CpG sites. A:T -- > G:C transitions were not found. All of the single-base deletions were at G:C base pairs.[Miller ML et al; Environ Mol Mutagen 35 (4): 319-327 (2000). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/10861950?dopt=Abstract" target=new>PubMed Abstract /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ A great amount of literature exists which conclusively demonstrates the carcinogenicity of Benzo(a)Pyrene. In all animal species tested to date (mouse, rat, hamster, rabbit, guinea pig, duck, newt, dog, monkey) and in fish, Benzo(a)Pyrene has proven carcinogenic. Benzo(a)Pyrene acts locally, as evidenced by tumor development at the site of administration. Benzo(a)Pyrene also acts systemically, however, an action best evidenced by pulmonary adenomas in mice resulting from any route of administration. Because Benzo(a)Pyrene is a procarcinogen, potency is directly dependent upon the levels of activation enzymes (ie, P450s, sulfotransferases); therefore, carcinogenic potency is exceptionally species- and condition-specific.[American Conference of Governmental Industrial Hygienists. Documentation of the TLV's and BEI's with Other World Wide Occupational Exposure Values. CD-ROM Cincinnati, OH 45240-1634 2007.] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ ... Analysis of dose-response data for benzo[a]-pyrene (BaP) and 6-nitrochrysene (6-NC) showed that tumor multiplicity for BaP also saturated at approximately 7 tumors/animal, whereas no similar saturation was found for 6-NC at up to 40 tumors/animal. Progression of lung adenomas to adenocarcinomas, as measured by the incidence of mice bearing malignant tumors, was essentially a linear function of dose. To facilitate comparison and maximize quantitative data obtainable from the newborn mouse assay-parameters were defined for tumor incidence (ED50), tumor

multiplicity (TM1.0) and tumor malignancy (malignancy index). Values for the ED50 and TM1.0 were similar for the same compound and a tumorigenic potency series of 6-NC greater than BaP greater than CPP was obtained corresponding to a ratio of approximately 1:10-25:76.5-135, respectively. The malignancy index, however, indicated increased adenocarcinoma induction in the order ... 6-NC greater than BaP ...[Busby WF Jr et al; Carcinogenesis 9 (5): 741-6 (1988). Available from, as of November 16, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/3365834?dopt=Abstract" target=new>PubMed Abstract /LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Four mg/kg /of Benzo(a)Pyrene/administered to pregnant rats during gestation produced no effects in the offspring, whereas 20 mg/kg resulted in a 20% tumor incidence.[Warshawsky D; Patty's Toxicology CD-ROM (2005). NY, NY: John Wiley &amp; Sons; Polycyclic and Heterocyclic Aromatic Hydrocarbons. Online Posting Date: April 16, 2001.] **PEER REVIEWED** /LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Ip administration of single doses of 10 mg Benzo(a)Pyrene produced immediate and sustained reduction in growth rate of young rats.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V32 214 (1983)] **PEER REVIEWED** /LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ ... Sterility /was observed/ in female /offspring of/ mice exposed to 40-160 mg/kg /of benzo(a)pyrene/ on gestation days 7-16.[Shepard, T.H. Catalog of Teratogenic Agents. 4th ed. Baltimore, MD: Johns Hopkins University Press, 1983., p. 52] **PEER REVIEWED** /LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ ... A dose of 5 mg/day /benzo(a)pyrene/ sc to pregnant rats, can cause death of all fetuses ... Oral admin of 10 mg/kg bw benzo(a)pyrene to CD-1 mice during pregnancy resulted in marked and specific reduction of gonadal wt but had no effect on body wt of ... male or female offspring. Reduction in fertility and reproductive capacity occurred. With 40 mg/kg bw/day ... almost complete sterility was observed in offspring of both sexes.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V32 214 (1983)] **PEER REVIEWED** /LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ ... /Among rats fed/ 1 mg /Benzo(a)Pyrene/ per g of diet during pregnancy ... many resorptions and dead fetuses /were observed,/ but only one malformed fetus /was noted/ from 7 litters.[Shepard, T.H. Catalog of Teratogenic Agents. 4th ed. Baltimore, MD: Johns Hopkins University Press, 1983., p. 52] **PEER REVIEWED** /LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ ... The in-utero toxicity in relation to the allelic differences at the Ah locus in mice /was studied/. A dose of 50-300 mg/kg /Benzo(a)Pyrene/ was given ip on days 7 or 10 ... The Ah genotype of individual fetuses /was identified/ by measurement of AHH inducibility and ... /showed/ that when the mothers were Ah nonresponsive, the fetuses with Ah responsive genotype showed decreased bw and higher resorption and malformation rates while Ah nonresponsive fetuses in the same uterus did not. The type of defect included mainly club foot, hemangioma, cleft lip, and cleft palate. All of

these defects tend to be associated with late organogenesis ... Using the same general protocol and 150 or 300 mg/kg on day 8 /another study/ confirmed the findings of ... toxicity (reduced fetal wt and incr resorptions) but ... not ... the same increase in malformations ... Only an increase in cervical ribs ... /which/ occurred among fetuses from Ah responsive mothers /was found/.[Shepard, T.H. Catalog of Teratogenic Agents. 4th ed. Baltimore, MD: Johns Hopkins University Press, 1983., p. 52] **PEER REVIEWED** /LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ The teratogenicity of benzo[a]pyrene (BaP), after direct injection into embryonal Swiss mice /was studied/. The compounds were dissolved in acetone and trioctanoin (1:1) and injected at doses ranging from 0.4 to 16.0 nmol/embryo on days 10, 12, and 14 of development. The transplacental effects of BaP given at the same gestational days and at comparable dose levels were also evaluated. The control groups received 0.5, 1.0, or 2.0 uL/embryo of vehicle on days 10, 12, or 14 of pregnancy, respectively. The fetuses were examined when they were 18 days old. On the basis of gross external and internal malformations, the administration of BaP (both transplacental and intraembryonal injection) caused no significant increase of malformed fetuses in any of the developmental stages considered.[Barbieri O et al; Cancer Res 46 (1): 94-8 (1986)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/3753553?dopt=Abstract" target=new>PubMed Abstract /LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Administration of benzo[a]pyrene (BaP, 50 mg/kg/day) to pregnant rats significantly increased glutathione S-transferase (GST) activity in placental tissue-extract ... This increase in the glutathione S-transferase system was not sufficient to protect the fetus. BaP affected the reproductive performance of pregnant rats by significantly increasing the number of resorptions and fetal wastage, and, also, by decreasing the fetal weight.[Cervello I et al; Placenta 13 (3): 273-80 (1992)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/1635913?dopt=Abstract" target=new>PubMed Abstract /LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Experimental evidence suggests that inorganic lead and benzo[a]pyrene (BaP) suppress the development of primordial oocytes during fetal life. We examined the single and combined effects of prenatal exposure to benzo[a]pyrene and moderate doses of lead. The fertility and ovarian morphology of Fl female NMRI mice in four treatment groups (nine mice per group) were investigated: control; lead (F0 given 1 g PbC12/L in drinking water until mating); benzo[a]pyrene (10 mg/kg bw daily by oral intubation on days 7-16 of F0 pregnancy); and combined lead and benzo[a]pyrene. Fl groups exposed prenatally to benzo[a]pyrene either alone or in combination with inorganic lead showed markedly reduced fertility with few ovarian follicles compared to controls, whereas the group exposed to lead only had measures comparable to the controls. Mice exposed to both lead and benzo[a]pyrene had a significantly longer gestation period (days to litter) compared to mice exposed only to benzo[a]pyrene, lead, or controls. There is a nonsignificant indication that the compounds together further reduce number of offspring, number of litters, and litter size. These results suggest that lead and benzo[a]pyrene have synergistic effects on impairment of fertility. The possibility of synergism may be of human relevance as inorganic lead and benzo[a]pyrene are ubiquitous environmental pollutants.[Kristensen P et al; Environ Health Perspect 103 (6): 588-90 (1995)] **PEER REVIEWED** <a

href="http://www.ncbi.nlm.nih.gov/pubmed/7556012?dopt=Abstract" target=new>PubMed Abstract /LABORATORY ANIMALS: Neurotoxicity/ ... The neurobehavioral effects of single oral doses of Benzo(a)Pyrene (25-200 mg/kg bw) on motor activity were examined in male F-344 rats at 2, 4, 6, 12, 24, 48, 72, and 96 hr post treatment. Parent Benzo(a)Pyrene and metabolites were measured at the above mentioned time points by reverse phase HPLC. The activity of several antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) and levels of malondialdehyde were determined at 6 and 96 hr in both the striatum and hippocampus of Benzo(a)Pyrene exposed rats. Suppression of motor activity (up to 70%) reached a maximum at 6 hr, but was reversible at 96 hr in all dose groups. The kinetics of disposition data show a strong link between Benzo(a)Pyrene metabolism and the onset and duration of behavioral effects. Benzo(a)Pyrene caused a 15-70% inhibition in the activity of superoxide dismutase and glutathione peroxidase and an enhancement in catalase and lipid peroxidation (up to 68%) in the striatum and hippocampus at 6 and 96 hr post treatment, respectively. These findings suggest that Benzo(a)Pyrene-induced acute neurobehavioral toxicity may occur through oxidative stress due to inhibition of the brain antioxidant scavenging system.[Saunders CR et al; Journal of Applied Toxicology: JAT 26 (5): 427-438 (2006). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/16858674?dopt=Abstract" target=new>PubMed Abstract /GENOTOXICITY/ ... Male Sprague-Dawley rats were dosed with 10 mg/kg benzo[a]pyrene (B[a]P) ip, 3 times/wk for 2 wk. At 1, 3, 7, 14, 28 and 56 days after the last treatment liver, lung, spleen and peripheral blood mononuclear cells (PBMNs) were sampled. The DNA adduct levels, as measured by the 32P-postlabelling technique, were significantly increased in all tissues, with lung having the highest levels. At day 14 total DNA adducts in lung, spleen and peripheral blood mononuclear cells were still > 50% of the level at day 1. The removal of total DNA adducts was found to be fastest in liver > spleen > peripheral blood mononuclear cells > lung. A consistent correlation of total adducts between the lung and peripheral blood mononuclear cells was observed. A major adduct, designated adduct 1, was detected in all tissues, while adduct 4 was only found in liver and lung. Adduct 5 was detected only in lung, where it constituted approximately 38-49% of total adducts and persisted at a higher level than either adduct 1 or adduct 4 for the entire post-exposure period. These results indicate that benzo[a]pyrene induced a significant increase in DNA adduct levels in all tissues tested and that total adducts in peripheral blood mononuclear cells reflect total lung adduct levels. DNA adducts were still readily detectable 56 days after exposure ceased...[Qu SX, Stacey NH; Carcinogenesis 17 (1): 53-9 (1996)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/8565137?dopt=Abstract" target=new>PubMed Abstract /GENOTOXICITY/ Dose-dependent increases in micronuclei were observed with 7,12-dimethylbenz(a)anthracene, benzo(a)pyrene, catechol, chrysene and urethane. These chemicals resulted in increased numbers of micronucleated keratinocytes, down to the lowest doses administered ... (0.128, 0.5, 2, 50 and 50 ug, respectively).[Baker RS, He S; Teratology 42 (3): 329-30 (1990)] **PEER REVIEWED** /GENOTOXICITY/ ... To determine whether co-exposure (Benzo(a)Pyrene/iron oxides) induces a real genotoxic activity or is only due to inhibition of DNA repair, the unscheduled DNA synthesis (UDS) assay was implemented in

vivo in the rat. The UDS assay was used to measure DNA repair in two cell types (lung cells and hepatocytes) of OFA Sprague-Dawley rats, 24 hr after endotracheal administration of a single dose of an iron oxide (hematite, Fe2O3) (0.75 mg), of Benzo(a)Pyrene (0.75 mg) or of Benzo(a)Pyrene (0.75 mg) coated on hematite particles (0.75 mg). No difference in UDS was observed in the two organs investigated in rats treated with iron oxide alone compared with control animals, while a significant increase in UDS was observed in lungs and liver of rats treated with Benzo(a)Pyrene alone compared with control animals. The main finding was a significant increase in UDS observed in both lung and liver cells of rats treated with Benzo(a)Pyrene coated on hematite when compared with those treated with Benzo(a)Pyrene alone ...[Garry S et al; Mutagenesis 18 (5): 449-455 (2003). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/12960414?dopt=Abstract" target=new>PubMed Abstract /GENOTOXICITY/ Two nitroaromatics, 6-nitrobenzo[a]pyrene (6-N-BaP) and 6-nitrochrysene (6-N-CRY), and the corresponding parent hydrocarbons, benzo[a]pyrene (BaP) and chrysene (CRY), were studied in in vitro transformation assays with Syrian hamster embryo (SHE) cells, BALB/3T3 and C3H10T1/2 mouse cell lines. The three cell systems showed different sensitivities to the transforming effects of the chemicals studied, SHE cells being the most efficient, followed by 3T3 cells and the last being C3H10T1/2 cells. In the SHE cell system all compounds were active. Considering the concentrations (in uM) and the transformation frequency BaP was the most active, followed by 6-N-BaP, 6-N-CRY and CRY. In the BALB/3T3 standard assay and in the C3H10T1/2 assay only BaP was clearly active. When used as initiators 6-N-BaP and 6-N-CRY were inactive in the C3H cell system. In conclusion 6-N-BaP appears less active in in vitro systems than the parent compound BaP; 6-N-CRY is probably negative since it is questionable in vitro and negative in mouse skin.[Sala M et al; Carcinogenesis 8 (4): 503-7 (1987). Available from, as of November 16, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/3829318?dopt=Abstract" target=new>PubMed Abstract /GENOTOXICITY/ Six polycyclic aromatic hydrocarbons were assayed for mutagenicity in the Ames test, in the presence of hepatic post-mitochondrial preparations isolated from the mouse, rat, hamster, pig, and man. Benzo[a]pyrene, dibenzo[a,i]pyrene and benz[a]anthracene gave a positive mutagenic response only in the presence of activation systems derived from the hamster. With the exception of the pig, activation systems derived from all animal species could convert 3-methylcholanthrene to mutagens, the hamster being the most efficient. With the exception of the rat and pig, all animal species activated 7,12-dimethylbenz[a]-anthracene to mutagens, the human preparation being the most effective followed by the hamster and mouse. Dibenz[a,h]anthracene was not activated by any of the hepatic preparations. It is concluded that, among the animal species studied the hamster is generally the most efficient in activating polycyclic aromatic hydrocarbons to mutagens in the Ames test.[Phillipson CE, Ioannides C; Mutat Res 211 (1): 147-51 (1989). Available from, as of September 17, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/2493576?dopt=Abstract" target=new>PubMed Abstract /GENOTOXICITY/ There is sufficient evidence that benzo[a]pyrene is active in numerous genotoxicity assays, including bacterial DNA repair, bacteriophage induction, and bacterial mutation; DNA binding, DNA repair, sister chromatid exchange, point mutation and transformation in mammalian

cells in culture; and in tests in mammals in vivo, including DNA binding, sister chromatid exchange, and chromosomal aberration.[Warshawsky D; Patty's Toxicology CD-ROM (2005). NY, NY: John Wiley &amp; Sons; Polycyclic and Heterocyclic Aromatic Hydrocarbons. Online Posting Date: April 16, 2001.] **PEER REVIEWED** /GENOTOXICITY/ A single topical application of 0.05 mL of 1% solution of Benzo(a)Pyrene in acetone to the interscapular area of hairless mice (hr/hr) induced an increase in the mitotic rate of epidermal cells.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V32 214 (1983)] **PEER REVIEWED** /GENOTOXICITY/ /Benzo(a)Pyrene/ (BaP) is embryotoxic to mice. Quantative effects are in part dependent on genetically-determined ability of cytochrome P450 monooxygenase system of mother &amp; fetus to be induced by polynuclear aromatic hydrocarbons. When mother is 'inducible', the genotype of fetus is relatively unimportant, since it appears that the active metabolites formed in mother can cross the placenta, causing fetal death or malformation. When the mother is 'non-inducible' ... the genotype of the fetus is important in that individual fetuses within 1 litter may or may not be inducible. Such observations help to explain why some fetuses may be more sensitive to action of teratogens and carcinogens than others within the same litter. An 'inducible' genotype is not the only factor involved in BaP reproductive toxicity ... since 'non-inducible' mice may sometimes be more sensitive to effects on fetal wt reduction and congenital anomalies due to BaP; Additionally, the incidence of external malformations may not be the same in mice of different genotypes after treatment with BaP, even if both dams and fetuses are inducible.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V32 215 (1983)] **PEER REVIEWED** /GENOTOXICITY/ The results of both the Salmonella/microsome mutagenicity assay and HPLC analysis were used to evaluate the interactions of binary mixtures of benzo[a]pyrene and several different polychlorinated aromatic hydrocarbons. Binary mixtures of either 2-nitro-3,7,8-trichlorodibenzo-p-dioxin or pentachlorophenol with benzo[a]pyrene produced synergism, whereas strictly additive effects were observed with mixtures of octa- or heptachlorodibenzo-p-dioxin and benzo[a]pyrene. ... HPLC analysis of the mixtures indicated that preincubation of benzo[a]pyrene with 2-nitro-3,7,8-trichlorodibenzo-p-dioxin increased the quantity of benzo[a]pyrene-7,8-dihydrodiol, and 9,10-dihydrodiol metabolites detected. The data suggest that nonmutagenic components of a complex mixture may alter the metabolism of promixate mutagens. Thus, in the present study, 2-nitro-3,7,8-trichlorodibenzo-p-dioxin appears to have inhibited the detoxication of benzo[a]pyrene metabolites.[Donnelly KC et al; Environ Mol Mutagen 16 (4): 238-45 (1990)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/2253602?dopt=Abstract" target=new>PubMed Abstract /GENOTOXICITY/ The genotoxicity of 15 polycyclic aromatic hydrocarbons was determined with the alkaline version of the comet assay employing V79 lung fibroblasts of the Chinese hamster as target cells. These cells lack the enzymes necessary to convert PAHs to DNA-binding metabolites. Surprisingly, 11 PAHs, ie, benzo[a]pyrene (BaP), benz[a]anthracene, 7,12-dimethylbenz[a]anthracene, 3-methylcholanthrene, fluoranthene,

anthanthrene, 11H-benzo[b]fluorene, dibenz[a,h]anthracene, pyrene, benzo[ghi]perylene and benzo[e]pyrene caused DNA strand breaks even without external metabolic activation, while naphthalene, anthracene, phenanthrene and naphthacene were inactive. When the comet assay was performed in the dark or when yellow fluorescent lamps were used for illumination the DNA-damaging effect of the 11 PAHs disappeared. ... Obviously, under standard laboratory illumination many PAHs are photo-activated, resulting in DNA-damaging species. This feature of PAHs should be taken into account when these compounds are employed for the initiation of skin cancer...[Platt, KL et al; Mutation Research 650 (2): 96-103 (2008). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/18160334?dopt=Abstract" target=new>PubMed Abstract /GENOTOXICITY/ Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon (PAH) and a potent mutagen/carcinogen found ubiquitously in the environment. B[a]P is primarily metabolized to diol epoxides, which react principally at N2-dG in DNA. BaP-N2-dG adducts have been shown to induce a variety of mutations, notably G-- > T, G-- > A, G-- > C and -1 frameshifts. Four stereoisomers of BaP-N2-dG (designated: [+ta]-;, [+ca]-, [-ta] and [-ca]) were studied by NMR in duplex 11mers in a 5'-CGC sequence context, and each adopted a different adduct conformation. Herein these four identical BaP-containing 11mers are built into duplex plasmid genomes and mutagenesis studied in Escherichia coli following SOS-induction. In nucleotide excision repair (NER) proficient E.coli, no adduct-derived mutants are detected. In NER deficient E.coli, G-- > T mutations dominate for all four stereoisomers [+ta]-, [+ca]-, [-ta] and [-ca]-BaP-N(2)-dG, and mutation frequency is similar. Thus, the mutagenic pattern for these four BaP-N2-dG stereoisomers is the same, in spite of the fact that they adopt dramatically different conformations in ds-oligonucleotides as determined by NMR. These findings suggest that adduct conformation must be fluid enough in the 5'-CGC sequence that the duplex DNA conformation can interconvert to mutagenic and non-mutagenic conformations during lesion-bypass...[Seo KYet al; Mutagenesis 20 (6): 441-448 (2005). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/16311255?dopt=Abstract" target=new>PubMed Abstract /GENOTOXICITY/ Benzo[a]pyrene induces cytochrome P-450 1A1 (CYP1A1) expression in rat polymorphonuclear leukocytes (PMNs) that upregulates expression of inducible nitric oxide synthase (iNOS). In the present study, the involvement of secondary signaling molecules in CYP1A1-mediated augmentation of iNOS expression in benzo[a]pyrene-treated rat PMNs was investigated. PMNs were isolated from the peripheral blood of controls and benzo(a)pyrene-treated rats. The expression and/or activity of CYP1A1, iNOS, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), and intracellular calcium ([Ca(2+)]i) concentrations were measured in control and benzo[a]pyrene-treated rat PMNs with and without alpha-naphthoflavone, aminoguanidine, genistein, pyrrolidine dithiocarbamate (PDTC), felodipine, or SB202190 pre-treatment. A significant elevation in CYP1A1 and [Ca(2+)]i was observed in benzo[a]pyrene-treated rat PMNs, which was significantly restored by alpha-naphthoflavone or genistein. Neither PDTC, SB202190, nor aminoguanidine altered the benzo(a)pyrene-mediated increase in [Ca(2+)]i. Although felodipine reduced the benzo[a]pyrene-mediated increase in [Ca(2+)]i, no significant change was observed in CYP1A1 expression and activity. Benzo[a]pyrene-augmented iNOS expression and activity in PMNs were significantly reverse by felodipine, genistein, or PDTC. Benzo[a]pyrene also induced TNF-alpha and IL-1beta production in PMNs, which was significantly reversed by genistein. The results demonstrated

the involvement of [Ca(2+)]i, tyrosine kinase, inflammatory cytokines, and NF-kappaB in CYP1A1-mediated iNOS expression in benzo(a)pyrene-treated rat PMNs.[Kumar A et al; Life sciences 81 (23-24): 1575-1584 (2007). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/17991490?dopt=Abstract" target=new>PubMed Abstract /GENOTOXICITY/ The mechanism of adduction of 2'-deoxyadenosine by styrene oxide and polycyclic aromatic hydrocarbon dihydrodiol epoxides has been explored using (15)N(6)-labeled adenine nucleosides. The extent of reaction at N1 versus N(6) was evaluated by (1)H NMR of the N(6) adducts after allowing Dimroth rearrangement to occur. Products arising from attack at N1 followed by Dimroth rearrangement exhibited a small two-bond (1)H-(15)N coupling constant (N1-H2 J approximately 13 Hz); products from direct attack exhibited a much larger one-bond (1)H-(15)N coupling constant (J approximately 90 Hz). In the case of styrene oxide, all of the N(6) beta adduct arose by initial attack at N1, whereas the majority (70-80%) of the N(6) alpha adducts came from direct attack. The styrene oxide reaction was also studied with a self-complementary oligodeoxynucleotide (24-mer) containing nine (15)N(6)-labeled adenine residues. NMR examination of the N(6) alpha- and beta-styrene oxide adducts isolated after enzymatic degradation of the 24-mer gave very similar results, indicating that N1 attack can occur readily even with a duplexed oligonucleotide. With the PAH dihydrodiol epoxides, only naphthalene dihydrodiol epoxide exhibited significant initial reaction at N1 (50%). No detectable rearranged product was seen in reactions with benzo[a]pyrene dihydrodiol epoxide or non-bay or bay region benz[a]anthracene dihydrodiol epoxide; interestingly, a small amount of N1 attack (5-7%) was seen in the case of benzo[c]phenanthrene dihydrodiol epoxide. It appears that initial attack at N1 is only a significant reaction pathway for epoxides attached to a single aromatic ring.[Kim HY et al; Chemical research in toxicology 13 (7): 625-637 (2000). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/10898595?dopt=Abstract" target=new>PubMed Abstract /GENOTOXICITY/ ... The effect of two dosing regimens on the mutagenicity of DiBenzo[a,l]Pyrene (DB[a,I]P and Benzo(a)Pyrene (BaP) in vivo /were investigated/ using the Big Blue(R) transgenic mouse system. /Investigators/ compared administration of a single highly tumorigenic dose of each PAH with a fractionated delivery of the same total dose administered over 5 days, with the expectation that PAH-induced AP sites would be produced at a greater margin above background levels in animals receiving the high single dose than in the animals receiving the fractionated doses. Treatment with DB[a,l]P yielded a 2.5-fold (single dose) to 3-fold (fractionated dose) increase in mutant frequencies relative to controls. Both single-dose and fractionated dose treatment regimens with BaP produced about a 15-fold increase in mutant frequencies compared to controls. The mutations induced by BaP and DB[a,l]P correlated with the stable covalent DNA adducts produced by each. These mutation results are consistent with the previously identified stable covalent DNA adducts being the promutagenic lesions produced by these two PAHs and do not support a major role for depurinating adducts, contributing to PAH-induced mutagenesis in mouse lung in vivo.[Leavitt SA et al; Mutagenesis 23 (6): 445-450 (2008). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/18573814?dopt=Abstract" target=new>PubMed Abstract /GENOTOXICITY/ The transplacental mutagenicity of three polycyclic

aromatic hydrocarbons, 7,12-dimethylbenz[a]anthacene (DMBA), 3-methylcholanthrene (MC) and benzo[a]pyrene (BP), was measured by an in vivo/in vitro mutation assay. Fetal sensitivity and dose-response characteristics with regard to transplacental mutagenesis by these compounds have never been quantified. In the current experiment, pregnant Syrian hamsters were exposed to these compounds at day 12 of gestation. Twenty-four hours later the fetuses were removed and their cells were allowed a 5-day expression time in culture. They were then seeded for colony formation and also for mutation selection by diphtheria toxin. DMBA at 0.2 mmol/kg (51.3 mg/kg) had an induced mutant frequency of 1.56 X10-4 mutants per surviving cell. This was 598 times the historical control. DMBA at 0.2 mmol/kg was 3.6 times more potent than the highly mutagenic positive control, ethylnitrosourea, at 1 mmol/kg. DMBA also caused a dose-dependent increase in cloning efficiency, which was highly correlated with mutation rate. BP and MC were less effective than DMBA, causing increased mutations that were 31.6 and 17.7 times the historical control, respectively, and for neither was there any correlation of mutation rate with cloning efficiency. The special effectiveness of DMBA as a transplacental mutagen may relate to its ability to cause increased cell division and fixation of DNA lesions as mutations.[Donovan PJ et al; Mutation research 554 (1-2): 111-120 (2004). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/15450409?dopt=Abstract" target=new>PubMed Abstract /GENOTOXICITY/ ... Benzo[a]pyrene (BaP), or its noncarcinogenic Benzo(e)Pyrene isomer, was incubated with cultured skin fibroblasts obtained from male RHA-J/J rats. These rats have a hereditary homozygous deficiency in bilirubin UDP-glucuronosyltransferase and demonstrate reduced xenobiotic glucuronidation, enhanced cytochrome p450-catalyzed bioactivation, covalent binding, and toxicity of acetaminophen and benzo(a)pyrene. Control fibroblasts were cultured from UDP-glucuronosyltransferase-normal congenic homozygous male RHA-(+/+) rats and male Wistar rats. The cells were incubated with 10 uM benzo(a)pyrene or B(e)P either for assessment of micronucleus formation or for quantifying the bioactivation and covalent binding of benzo(a)pyrene and the glucuronidation of its hydroxylated metabolites. Compared to control fibroblasts incubated only with buffer, micronucleus formation was not enhanced by either DMSO vehicle or BeP. In contrast, BaP significantly enhanced micronucleus formation in all cells, and UDP-glucuronosyltransferase-deficient cells (RHA-J/J) had a 2-fold higher BaP-initiated micronucleus formation compared to UDP-glucuronosyltransferase-normal cells (RHA-(+/+) (P < 0.05). Glucuronidation of total BaP metabolites was 10% lower in RHA-J/J UDP-glucuronosyltransferase-deficient fibroblasts, and the covalent binding of BaP to protein, reflective of an electrophilic reactive intermediate and DNA-alkylating agent, was up to 3-fold higher in RHA-J/J UDP-glucuronosyltransferase-deficient fibroblasts or fibroblast homogenates compared to UDP-glucuronosyltransferase-normal controls (P < 0.05). In fibroblast homogenates, addition of the UDP-glucuronosyltransferase cosubstrate UDP-glucuronic acid reduced BaP covalent binding ... . There was a highly significant correlation between decreasing glucuronidation of BaP metabolites and increasing bioactivation and covalent binding of BaP (r = -0.889; P = 0.0181 in fibroblasts from RHA-J/J and RHA-(+/+) rat strains, indicating an important genoprotective role for UDP-glucuronosyltransferase. These results provide ... evidence that hereditary UDP-glucuronosyltransferase deficiencies may enhance susceptibility to chemical carcinogenesis and suggest that skin fibroblasts may provide a useful and highly sensitive model for human risk assessment.[Vienneau DS et al; Cancer Res 55 (5): 1045-51 (1995).

Available from, as of April 1, 2010:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/7866987?dopt=Abstract" target=new>PubMed Abstract /GENOTOXICITY/ The ability of three purified forms of rat liver cytochrome P450 to metabolically activate benzo[a]pyrene to mutagenic products was examined using Salmonella typhimurium strains TA98 and G46 in a reconstituted monooxygenase system. The isozymes examined were cytochrome P450-PB (the major phenobarbital inducible form), and the two major 3-MC inducible forms (cytochromes P448 (52,000 mol wt) and P448 (55,000 mol wt)). Only cytochrome P448(55) metabolizes benzo[a]pyrene and its 7,8-dihydrodiol derivative to mutagenic products.[Robertson IG et al; Carcinogenesis 4 (1): 93-6 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6295661?dopt=Abstract" target=new>PubMed Abstract /ALTERNATIVE and IN VITRO TESTS/ Cytochrome P450 1B1 (CYP1B1), an extrahepatic enzyme inducible by smoking, is overexpressed in many tumors and catalyzes the metabolic activation of procarcinogens such as polycyclic aromatic hydrocarbons. In humans, CYP1B1 is genetically polymorphic and five common missense mutations causing amino acid substitution have been identified. This study investigated CYP1B1 haplotypes present in a Spanish population ... . CYP1B1*1, CYP1B1*2, CYP1B1*3, CYP1B1*4, CYP1B1*6, and CYP1B1*7, encoding combinations of the Arg48Gly, Ala119Ser, Leu432Val, Asn453Ser, and Ala443Gly amino acid substitutions, were present at frequencies of 14.3%, 25.5%, 38.8%, 18.1%, 0.4%, and 2.6%, respectively. The variant CYP1B1 forms were heterologously expressed with human reductase in Saccharomyces cerevisiae and kinetic analysis of benzo[a]pyrene metabolism was carried out. CYP1B1.7, having the amino acid substitutions Arg48Gly, Ala119Ser, Leu432Val, and Ala443Gly, exhibited a significantly decreased capacity (P < 0.001) for the formation of (+/-)-benzo[a]pyrene-trans-7,8-dihydrodiol from benzo[a]pyrene as indicated by lower intrinsic clearance (Vmax/Km). A somewhat decreased clearance was observed for CYP1B1.4, whereas no significant differences in kinetic properties among the remaining variant enzymes were observed as compared with CYP1B1.1. Thus, genetic polymorphism in the CYP1B1 gene, as defined by the haplotypes investigated, might cause interindividual differences in susceptibility (e.g., to lung cancer induced by smoking). The results indicate the necessity to make molecular epidemiologic investigations regarding the association of the specific CYP1B1 haplotypes and cancer risk.[Aklillu E et al; Cancer Research 65 (12): 5105-5111 (2005). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/15958554?dopt=Abstract" target=new>PubMed Abstract /ALTERNATIVE and IN VITRO TESTS/ In vitro models demonstrated that /benzo[a]pyrene (BaP)/ ... rapidly induced apoptosis in primary pre-B cells and in the /murine/ pro/pre-B cell line, BU-11.[Klaassen, C.D. (ed). Casarett and Doull's Toxicology. The Basic Science of Poisons. 7th ed. New York, NY: McGraw-Hill, 2008., p. 526] **PEER REVIEWED** /ALTERNATIVE and IN VITRO TESTS/ ... The role of the aryl hydrocarbon receptor (AHR) in the production of reactive oxygen species (ROS) by its cognate ligands and the consequent effect on CYP1A1 activity, mRNA and protein expressions /was investigated/ ... Hepa 1C1C7 cells wild-type (WT) and C12 mutant cells, which are AHR-deficient, were incubated with increasing concentration of the AHR-ligands, benzo[a]pyrene (BaP) (0.25-25 uM), 3-methylcholanthrene (3MC, 0.1-10 uM), and beta-naphthoflavone (betaNF, 1-50 uM). The studied AHR-ligands dose-dependently increased

lipid peroxidation in WT but not in C12 cells. However, only BaP and betaNF, at the highest concentrations tested, significantly increased H2O2 production in WT but not C12 cells. The increase in lipid peroxidation and H2O2 production by AHR-ligands were accompanied by a decrease in the CYP1A1 catalytic activity but not mRNA or protein expressions, which were significantly induced in a dose-dependent manner by all AHR-ligands, suggesting a post-translational mechanism is involved in the decrease of CYP1A1 activity...[Elbekai RH, et al; Free Radic Res 38 (11): 1191-1200 (2004). Available from, as of November 25, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/15621696?dopt=Abstract" target=new>PubMed Abstract /ALTERNATIVE and IN VITRO TESTS/ Dolphin kidney cells (CDK) were exposed in vitro to benzo[a]pyrene (BaP) in the presence or absence of 2,3,7,8-tetrachlorodibenzo(p)dioxin (TCDD), a cytochrome P450-inducing agent, and/or alpha-naphthoflavone (alpha NF), an inhibitor of cytochrome P450 induction. Benzo[a]pyrene inhibited mitosis in dolphin kidney cells in a dose-dependent manner... Benzo[a]pyrene treatment initiated both (3H)-thymidine incorporation and the increased alkali liability of DNA functions of the initiation of excision repair. Cells pre-treated with 2,3,7,8-tetrachlorodibenzo(p)dioxin and then exposed to BaP exhibited increased BaP-DNA adduct levels and increased DNA excision repair. These data indicate that dolphin cells metabolized BaP in vitro as a function of cytochrome P450-associated activities, that BaP metabolites covalently bound to cellular DNA and initiated excision repair...[Carvan MJ 3rd et al; Chemosphere 30 (1): 187-98 (1995)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/7874466?dopt=Abstract" target=new>PubMed Abstract /ALTERNATIVE and IN VITRO TESTS/ ... Naphthalene, phenanthrene, pyrene, chrysene, and benzo[a]pyrene (BaP) were administered to rats for 3 days (25-128 mg/kg/day) and the responses compared with those of model /CYP/ inducers. PAH treatment increased the CYP1A-catalyzed activity of pyrene 1-hydroxylation and 7-ethoxyresorufin O-deethylation in rat liver by up to 28- and 279-fold, and in rat lung by up to 22- and 51-fold, respectively. 1-Naphthol (hUGT1A6), 1-hydroxypyrene (hUGT1A6/1A9), and entacapone (hUGT1A9) are markers of PAH-glucuronidating human uridine diphosphate-glucuronosyltransferases (UGT). These activities increased up to 6.4-fold in rat liver and up to 1.9-fold in rat lung. NADPH:quinone oxidoreductase 1 (NQO1) and glutathione S-transferase activities increased up to 5.3- and 1.6-fold (liver), and up to 4.4- and 1.4-fold (lung), respectively. CYP1A showed the best liver-to-lung relationship (R (2 )=( )0.90). The inducing efficiency by PAHs differed extensively: control < chrysene < < pyrene phenanthrene, naphthalene > 60-fold), many times greater than the experimental (inducible/constitutive) variation in the rat. Kinetics of 1-hydroxypyrene glucuronidation showed two low-K (m) forms both in rat and human lung. Since the 2-4-ring PAHs (major constituents) were poor enzyme inducers, it appears that the PAH-metabolizing pathways are mainly induced by BaP-type minor constituents. ...[Elovaara E et al; Archives of toxicology 81 (3): 169-182 (2007). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/16906435?dopt=Abstract" target=new>PubMed Abstract /ALTERNATIVE and IN VITRO TESTS/ Polycyclic aromatic hydrocarbons (PAHs) are activated by cytochrome P450 (CYP) isozymes, and a subset of the reactive metabolites generated is detoxified via conjugation with glutathione (GSH) by specific glutathione S-transferases (GSTs) ... V79MZ cells stably transfected with either human or rat cytochrome P4501A1 (CYP1A1) /were used/, alone or in combination with human GSTP1 (hGSTP1),

to examine the dynamics of activation versus detoxification of benzo[a]pyrene (B[a]P), dibenzo[a,l]pyrene (DB[a,l]P), and their dihydrodiol metabolites. The cytotoxicity of B[a]P or DB[a,l]P was 9-11-fold greater in cells expressing human, as compared to rat CYP1A1, despite similar enzymatic activities. Co-expression of the hGSTP1 with the hCYP1A1 conferred 16-fold resistance to B[a]P cytotoxicity, compared to only 2.5-fold resistance when hGSTP1 was co-expressed with rat CYP1A1. The lower B[a]P cytotoxicity in the cells expressing rat CYP1A1, and weaker protection by hGSTP1 co-expression in these cells, were attributable to the much lower fraction of B[a]P metabolism via formation of the 7,8-dihydrodiol intermediate by the rat CYP1A1 compared to hCYP1A1. Resistance to the DB[a,l]P cytotoxicity conferred by hGSTP1 expression was also greater in cells co-expressing hCYP1A1 (7-fold) as compared to cells co-expressing rCYP1A1 ( < 2-fold). Resistance to B[a]P conferred by hGSTP1 was closely correlated with the activity level in two clonal transfectant lines with a 3-fold difference in hGSTP1-1 specific activity. Depletion of GSH to 20% of control levels via pretreatment with the de novo GSH biosynthesis inhibitor buthionine sulfoximine reduced the protection against B[a]P cytotoxicity by hGSTP1 from 16-fold to 5-fold, indicating that catalysis of conjugation with GSH, rather than binding or other effects, is responsible for the resistance. The cytotoxicity of the dihydrodiol intermediates of B[a]P or DB[a,l]P was much greater, and similar in cell lines expressing either human or rat CYP1A1. Again, however, the protection conferred by hGSTP1 co-expression was 2-5-fold greater in cells with hCYP1A1 than with rCYP1A1 expression. These results indicate that GST expression can effectively limit cytotoxicity following activation of B[a]P by human or rat CYP1A1, but is less effective as a defense against exposure of cells to the intermediate metabolite B[a]P-7,8-dihydrodiol.[Kabler SL et al; Chemico-biological interactions 179 (2-3): 240-246 (2009). Available from, as of November 23,2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/19330882?dopt=Abstract" target=new>PubMed Abstract /IMMUNOTOXICITY/ Marked differences in toxic effects of Benzo(a)Pyrene have been reported in different strains of mice depending on ... genetic constitution. The Ah locus, which determines inducibility of aryl hydrocarbon hydroxylase, appears to be of particular importance ... Oral admin of about 120 mg/kg bw Benzo(a)Pyrene per day with diet induced aplastic anemia in nonresponsive (poorly inducible) AKR/N mice (Ah(d)/Ah(d) type) and death within 4 wk, whereas responsive (markedly inducible) mice (Ah(b)/Ah(b) type) remained healthy for at least 6 mo. In former, bone marrow was hypocellular with myeloid precursors and promegakaryocytes. When Benzo(a)Pyrene was injected ip (500 mg/kg bw) instead of being given orally (120 mg/kg bw), survival time of responsive mice (Ah(b)/Ah(b) type) was ... significantly shorter than that of nonresponsive mice (Ah(d)/Ah(d) type). These differences may be explained in part by the greater capacity of bowel and liver of responsive mice to detoxify an orally admin dose of Benzo(a)Pyrene metabolically. However, if the hydrocarbon reaches bone marrow and other distal tissues in responsive mice, it is metabolized to toxic metabolites to a greater extent.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V32 214 (1983)] **PEER REVIEWED** /IMMUNOTOXICITY/ In utero exposure to the environmental contaminant benzo[a]pyrene (BaP) was found to alter expression of murine thymocyte and liver fetal cell-surface markers. Pregnant mice were treated (via gavage) with 0, 50, 100, or 150 mg BaP/kg/d on gestational days ... 13-17, and

offspring were examined on gestational day 18. Severe thymic atrophy and cellular depletion were found in benzo[a]pyrene-exposed fetal mice. Flow cytometric analysis indicated that the BaP treatment resulted in a significant decrease in the percentage of CD4-8+ fetal thymocytes, as well as significantly increased CD4-8- and CD4-8+ thymocytes. Staining of thymocytes with anti-mouse heat-stable antigen (HSA) and CD8 monoclonal antibodies produced similar results. These data suggest that BaP, in addition to producing thymic hypocellularity, inhibits normal thymocyte naturation processes. The BaP treatment was also found to decrease total fetal liver cellularity including numbers of cells within resident hematopoietic subpopulations. In particular, prolymphocytic cells, identified by CD44 and CD45R antigen expression and by presence of nuclear terminal deoxynucleotidyl transferase (TdT), were significantly decreased in animals gestationally exposed to BaP...[Holladay SD, Smith BJ; J Toxicol Environ Health 42 (3): 259-73 (1994)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/8021962?dopt=Abstract" target=new>PubMed Abstract /IMMUNOTOXICITY/ Sustained cell-mediated immunosuppression after exposure to benzo(a)pyrene (BP) implicates adverse effects on T cell ontogeny. /The authors/ hypothesize that quantitative and qualitative deficiency is a function of changes that occur in development of T cell subsets leading to persistent defective T cell behavior. By serology, fetal thymus (FT), fetal liver (FL), and fetal spleen cells expressing T antigens are disoriented. In perinatal thymus, Thy1+, Lyt1+, Lyt2+ are reduced; in FL Thy1 are reduced, Lyt1 unchanged and Lyt2 enhanced. For perinatal spleen Thy1 are reduced, but enhanced post-birth (also for Lyt2). Gestation thymic mixed lymphocyte response (MLR) is enhanced, but depressed post-birth. Isolated (magnetic activated cell sorting) T subsets (including L3T41) are deficient in the presence of concanavalin A, while in FL and postnatal cells (thymus and spleen) MLR deficiency occurs for Thy1 and L3T4 cells. An increase in double negatives and decrease in double positives occurs in the thymus as seen by flow cytometry. In 18 day gestation FL there is a decrease in L3T4 cells, and in FT rearranged V(gamma3)J(gamm1) is re-expressed. Finally, benzo[a]pyrene-7,8-diol-9,10-epoxide (BP metabolic intermediate) is detected in FL and in thymus after birth. Taken together, the data indicate BP disruption of T cell embryogenesis which persists post-birth. Thus, subsequent anomalus T cell behavior likely plays a significant role in enhanced growth of nascent neoplasms possibly by defective recognition of antigens.[Urso P et al; FASEB J 8 (4): A482 (1994)] **PEER REVIEWED** /OTHER TOXICITY INFORMATION/ The potent mutagen/carcinogen benzo[a]pyrene (B[a]P) is metabolically activated to (+)-anti-B[a]PDE, which induces a full spectrum of mutations (eg GC-- > TA, GC-- > AT, etc.). One hypothesis for this complexity is that different mutations are induced by different conformations of its major adduct [+ta]-B[a]P-N2-dG when bypassed during DNA replication (probably by different DNA polymerases). Previous molecular modeling studies suggested that B[a]P-N2-dG adducts can in principle adopt at least 16 potential conformational classes in ds-DNA. Herein /investigators/ report on molecular modeling studies with the eight conformations most likely to be relevant to base substitution mutagenesis in 10 cases where mutagenesis has been studied in ds-DNA plasmids in E. coli with B[a]P-N2-dG adducts of differing stereoisomers and DNA sequence contexts, as well as in five cases where the conformation is known by NMR. Of the approximately 11,000 structures generated in this study, the computed lowest energy structures are reported for 120 cases (ie eight conformations and 15 examples), and their conformations compared. Of the eight conformations, four are virtually always computed to be high in energy. The remaining four lower energy conformations include two with the

BP moiety in the minor groove (designated: BPmi5 and BPmi3), and two base-displaced conformations, one with the dG moiety in the major groove (designated: Gma5) and one with the dG in the minor groove (designated: Gmi3). Interestingly, these four are the only conformations that have been observed for B[a]P-N2-dG adducts in NMR studies. Independent of sequence contexts and adduct stereochemistry, BPmi5 structures tend to look reasonably similar, as do BPmi3 structures, while the base-displaced structures Gma5 and BPmi3 tend to show greater variability in structure. A correlation was sought between modeling and mutagenesis results in the case of the low energy conformations BPmi5, BPmi3, Gma5 and Gma3. Plots of log[(G-- > T)/(G-- > A)] versus energy[(conformation X)-(conformation Y)] were constructed for all six pair wise combinations of these four conformations, and the only plot giving a straight line involved Gma5 and Gmi3.[Lee CH et al; Mutation research 529 (1-2): 59-76 (2003). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/12943920?dopt=Abstract" target=new>PubMed Abstract /OTHER TOXICITY INFORMATION/ Newborn animals treated with benzo[a]pyrene or dimethylbenz[a]anthracene have been shown to develop higher incidences of liver and lung tumors than animals treated later in life. The age-dependent susceptibility to these two compounds may be dependent on their ability to act as mutagens. Analyses of data on a variety of chemicals for which tumor incidences following perinatal exposure were compared with those following adult exposure show that the increased susceptibility may be linked to a mutagenic mechanism of action.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Industrial Exposures, v 92 (2005). Summary available from, as of November 29, 2009: http://monographs.iarc.fr/ENG/Meetings/index1.php] **PEER REVIEWED** ECOTOXICITY EXCERPTS: /BIRDS and MAMMALS/ Thirty-four ducks were given single intratracheal dose of 50-200 mg BaP in Tween 80. Survival rate was poor. One ... /duck/ developed a lung carcinoma, and two had bronchial squamous metaplasia.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V3 109 (1973)] **PEER REVIEWED** /AQUATIC SPECIES/ Poeciliopsis lucida and Poeciliopsis monacha are freshwater viviparous fishes susceptible to tumorigenesis by exposure to waterborne procarcinogens. The hepatic monooxygenase system and the uptake, toxicity, and distribution of benzo[a]pyrene (BP) were characterized as a first step in exploring relationships between xenobiotic metabolism and cancer in these fishes. Waterborne BP was lethal at a dose of 3.75 mg/L with a 24 hr exposure. During a 24 hr exposure to 1.0 mg/L (3.97 umol/L) BP, an average of 8.27 nmol of BP was taken up per fish. Of this total, 64-70% was in the gallbladder or gut, indicating rapid metabolism and excretion. Basal levels of aryl hydrocarbon hydroxylase (AHH) activity were fairly high, about 0.6 nmol/min/mg. Maximal induction by BP occurred at a dose of 1.0 mg/L, but with aryl hydrocarbon hydroxylase activities only about twice the levels in untreated fish. Sensitivity to inhibition by alpha-naphthoflavone increased slightly in treated fish. Induced aryl hydrocarbon hydroxylase and also 7-ethoxyresorufin O-deethylase activities declined slowly after a single treatment, approaching pre-exposure levels after 7 days ...[Kathryn A et al; Am Soc Pharm Exp Ther 15 (4): 449 (1987)] **PEER REVIEWED**

/AQUATIC SPECIES/ Buffalo river sediment extracts contained polynuclear aromatic hydrocarbons (PAH) which caused skin darkening, hyperplasia, skin papillomas, mild coarsening and local pigmentations in the brown bullhead (Ictalurus nebulosus). Sixteen PAH were identified in the sediment extract: fluorene, phenanthrene, anthracene, fluoranthene, 2-methylphenanthrene, pyrene, 2-methylanthracene, benzanthracene, chrysene, perylene, benzo[f]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, dibenz[a,h]anthracene, benzo[g,h,i]perylene, and indeno[1,2,3-c,d]pyrene.[Black JJ; Polynucl Aromat Hydrocarbons Int Symp 7th 99-11 (1983)] **PEER REVIEWED** /AQUATIC SPECIES/ Histological and skeletal examinations were performed on rainbow trout alevins reared in 0.00, 0.08, 0.21, 0.39, 1.48, 2.40, or 2.99 ng/mL aqueous benzo[a]pyrene (BaP). Nuclear pycnosis and karyorrhexis were most common in neuroectodermal and mesodermal derivatives and in liver of BaP-treated alevins. Microphthalmia was noted in 17% of the test fish and was frequently associated with a patent optic fissure. Depressed mitotic rates in the retina and brain, but not liver, were seen in alevins reared in 0.21 to 1.48 ng/mL aqueous BaP. Test alevins had a significantly higher incidence of skeletal malformations in the skull and vertebral column and abnormalities of vertebral arcualia often corresponded to areas of kyphoscoliotic flexures. The ecological significance of such morphological abnormalities would be decreased feeding and growth and inability to escape predation, leading to reduced survival. Persistent mixed function oxygenase induction in less affected larvae would lead to continuing production of cytotoxic, mutagenic, and carcinogenic BaP metabolites resulting in anemia, impaired ability to respond to environmental stress and disease, and possibly latent tumorigenesis.[Hose JE et al; Arch Environ Contam Toxicol 13 (6): 675-84 (1984)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6517617?dopt=Abstract" target=new>PubMed Abstract /AQUATIC SPECIES/ These studies investigated the maternal transfer of xenobiotic ligands in the estuarine mummichog (Fundulus heteroclitus). The common environmental contaminants 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and benzo[a]pyrene (B[a]P) were shown to accumulate in maturing oocytes of gravid F. heteroclitus. In vivo, time-course experiments with gravid female fish demonstrated time- and dose-dependent changes in oocytic accumulation of 3H-TCDD and 14C-B[a]P. In studies with 14C-B[a]P, both total radiochemical content and the composition of 14C-B[a]P metabolites in these extracts presented an accumulation profile that mirrored the profiles observed in sera from dosed fish reported previously. Furthermore, the accumulation of both 3H-TCDD and 14C-B[a]P was related to oocyte maturational state (i.e., size) and, correspondingly, to vitellogenin (VTG) uptake. Although VTG uptake is critical for proper oocyte growth and early-life-stage development, analysis of these data suggests an additional role for VTG as a vector of maternal transfer for both 3H-TCDD and 14C-B[a]P. ...[Monteverdi GH, Di Giulio RT; Environ Toxicol Chem 19 (10): 2512-8 (2000)] **PEER REVIEWED** /AQUATIC SPECIES/ Lobster (Homarus americanus) in Maine and the spiny lobster (Panulirus argus) in Florida were selected as exptl invertebrate models for studies of the disposition and metabolism of xenobiotics. Hepatopancreas microsomes from both species contained relatively high amounts of cytochrome p450 ( > = 1 nmol/mg protein), but NADPH-dependent monooxygenase activity was very low or undetectable with several substrates, including benzo(a)pyrene. NADPH-dependent cytochrome c reductase activity was also very low in these microsomes.

(14)C-Benzo[a]pyrene (1 mg/kg) was metabolized and excreted very slowly after intracardial administration to lobsters. The half-life for disappearance of radiolabel was approximately 2 mo, and most of the radioactivity was stored in the hepatopancreas. Similar studies in the spiny lobster demonstrated that metab and excretion were considerably faster in this species (half-life approximately 1 wk in the summer and approximately 2 wk in the winter).[Bend JR et al; Proc Int Symp Princess Takamatsu Cancer Res Fund 11: 179-94 (1981)] **PEER REVIEWED** /AQUATIC SPECIES/ The teratogenic effects of environmental levels of ... benzo[a]pyrene, were investigated using the purple sea urchin (Strongylocentrotus purpuratus) and were related to embryonic cytotoxicity and genotoxicity as evidenced by the presence of aberrant chromosome arrangements during mitosis. Developmental abnormalities were observed in gastrulae treated with initial benzo(a)pyrene concentrations of 1-50 ng/mL relative to solvent (ethanol)-treated control embryos. However, genotoxic effects were significant at the lowest benzo(a)pyrene dose tested, 0.5 ng/mL. Micronucleus formation, a widely used test of genotoxicity in mammals was observed in embryos exposed to 1 to 50 ng/mL of benzo[a]pyrene. the results from this cytogenetic analysis demonstrated that mitotic inhibition and aberrations are more sensitive indicators of benzo[a]pyrene induced damage than are developmental effects.[Hose JE et al; Arch Environ Contam Toxicol 12 (3): 319-32 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6309101?dopt=Abstract" target=new>PubMed Abstract /AQUATIC SPECIES/ ...In this study, ... the survivorship of fathead minnow larvae two generations removed from an exposure to the potent mutagen benzo[a]pyrene /was studied/. The F2 broods with a grandparental exposure history showed a marked decrease in survival. In the highest-exposure group, reproductive capacity and larval survivorship were significantly lower than the solvent control.[White PA et al; Environ Toxicol Chem 18 (8): 1843-7 (1999)] **PEER REVIEWED** /AQUATIC SPECIES/ Food-borne benzo[a]pyrene (BaP) was administered daily to juvenile grouper (Epinephelus areolatus) at two environmentally realistic concentrations (a low dose of 0.25 ug BaP/g body wt/day and a high dose of 12.5 ug BaP/g body wt/day) to investigate and relate temporal changes in body burden of BaP, hepatic ethoxyresorufin-O-deethylase (EROD) activities, growth, RNA:DNA ratio, estradiol, testosterone, and triiodothyronine (T3). After feeding with BaP diets for four weeks, fish were fed with normal diet for another four weeks to study recovery of the various biomarkers during the depuration period. After one week of exposure, both body muscle BaP burdens and hepatic EROD activities significantly increased. Body burdens were stable in tissues until the fourth week of exposure, when concentrations in the high-dose group increased markedly, at which time a concomitant decrease in EROD was found. During the depuration period, body burdens decreased in the second week, and EROD declined in the first week. Growth and RNA:DNA ratio were unaltered. Despite large variations found in sex steroid levels, elevation of testosterone was clearly evident in the fourth week, showing that BaP may disrupt the balance of sex steroids in fish. Significantly, increases in plasma-free T3 concentrations were found in the fourth week of exposure and the first week of depuration, suggesting that development and reproduction may potentially be at risk during chronic exposures. ...These hormonal disturbances are not persistent and that normal hormonal levels can be restored soon after contamination is abated.[Wu RSS et al; Environ Toxicol Chem 22 (7): 1568-73 (2003)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/12836983?dopt=Abstract" target=new>PubMed Abstract

/AQUATIC SPECIES/ Since 1995, high incidences of deformed frogs have been documented in Kitakyushu, Japan. In this area, relatively high concentrations of DDT, trinitrotoluene (TNT), their metabolites (p,p'-dichlorodiphenyldichloroethylene [DDE], p,p'-dichlorodiphenyldichloroethane [DDD], 2-amino-4,6-dinitrotoluene [2ADNT], and 4-amino-2,6-dinitrotoluene [4ADNT]), and benzo[a]pyrene [BaP]) have been identified from field samples. ...The Xenopus laevis embryos (frog embryo teratogenesis assay-Xenopus, FETAX) /was used/ to examine the developmental toxicity of these compounds. Both DDE and BaP were considered nearly nontoxic in embryonic development because they induced low ( < 10%) mortality and malformation incidence even at the highest concentrations tested (DDE, 393 uM; BaP, 13.2 uM). ...[Saka M; Environ Toxicol Chem 23 (4): 1065-73 (2004)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/15095906?dopt=Abstract" target=new>PubMed Abstract /AQUATIC SPECIES/ A bioassay was developed to assess the toxic effects of ingested prey contaminated by polycyclic aromatic hydrocarbons (PAHs) using the teleost Fundulus heteroclitus as a predator and the polychaete Nereis virens as a benthic vector. Ten groups of nine male adult Fundulus were exposed for 21 days to 10 different diets of Nereis contaminated with benzo[a]pyrene (BaP) by spiking dead Nereis with BaP (spiked Nereis [SN] diets, 0-26 ug of BaP per gram dry wt) or by exposing living Nereis to a diet, to sediments, or to both contaminated with BaP (exposed Nereis [EN] diets, 0-16 ug/g dry wt). Another group was exposed to commercial fish food, used as reference diet. Condition and prevalence of histopathological changes were not affected. Exposure to the SN diets containing at least 3.5 ug of BaP per gram dry weight caused an induction of ethoxyresorufin-O-deethylase activity in the intestine but not in the liver. In contrast, fish exposed to the highest doses (13.4 ug of BaP per gram dry wt) had increased cellular proliferation rate in the liver but not in the intestine. Quantifiable levels of free BaP tetrol-like metabolites were detected in the bile of fish exposed to diets containing more than 6.8 ug/g dry weight of BaP, and exhibited a dose-response relationship in fish exposed to SN diets. For a similar dose of BaP, EN and SN diets had similar effects. Thus, the BaP metabolic products that could have been produced in Nereis apparently did not contribute to the biomarkers responses...[Couillard CM et al; Environ Toxicol Chem 28 (4): 772-81 (2009)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/19391678?dopt=Abstract" target=new>PubMed Abstract /AQUATIC SPECIES/ The need to understand chemical uptake, distribution, and metabolism in embryonic and larval fish derives from the fact that these early life stages often exhibit greater sensitivity to xenobiotic compounds than do adult animals. In this study, a 6-hr acute waterborne exposure immediately after fertilization was used to quickly load the egg with benzo[a]pyrene (BaP). ... Embryonic metabolism of BaP was evident ... prior to liver formation or heart development. A major product of this metabolism was identified ...as BaP-3-glucuronide. ...Metabolites were sequestered within the yolk, biliary system, and gastrointestinal tract. When the gastrointestinal tract became patent a few days after hatch, the metabolites were rapidly eliminated... It remains unclear whether metabolism of BaP in medaka embryos leads to the formation of DNA adducts associated with genotoxic effects or yields metabolites that later lead to other toxicity in juveniles or adults.[Hornung MW et al; Toxicological Sciences: an official journal of the Society of Toxicology 100 (2): 393-405 (2007). Available from, as of November 23, 2009:] **PEER REVIEWED** <a

href="http://www.ncbi.nlm.nih.gov/pubmed/17804863?dopt=Abstract" target=new>PubMed Abstract /AQUATIC SPECIES/ In vivo metabolism and depuration of benzo[a]pyrene (BaP) was studied in the blue mussel Mytilus edulis. In one experiment, the animals were injected with 3H-BaP and thereafter exposed to either a high (H) or a low (L) concentration of the alga Isochrysis galbana. Mussels were sampled after 2, 4, 8, 16, and 32 days and temporal changes in the metabolite profiles were analyzed using nonpolar and polar solvents. The metabolic fate and the depuration rate of BaP from the two feeding groups were compared. In a second experiment, mussels were exposed to [3H]-BaP or [14C]-BaP either injected or via the surrounding water, and the tissue distribution of radiolabeled compound was studied. The half-life of BaP was 15-17 days and unaffected by the food concentration. The metabolic profile differed slightly between the two treatments. Animals in the L group had a significant peak in the quantity of macromolecular adducts eight days after the injection, whereas the H group had a fairly stable amount of adducts throughout the experimental period. The tissue distribution study revealed that the radiolabeled compound was mainly present in the epithelial cells of the hepatopancreas and the ciliated epithelial cells of the gills. A fraction of the radioactivity was firmly bound.[Magnusson K et al; Environ Toxicol Chem 19 (11): 2683-90 (2000)] **PEER REVIEWED** /AQUATIC SPECIES/ Juvenile turbot (Scophthalmus maximus) were injected intraperitoneally with either corn oil or 5 mg/kg benzo[a]pyrene (BaP) dissolved in corn oil and sampled I and 3 days after injection. After 1 day, no elevation of 7-ethoxyresorufin O-deethylase (EROD) activity was observed, however bile metabolites (BaP-7,8 dihydrodiol representing 70% of the total metabolites) and a single hepatic DNA adduct spot (0.47 adducts/10(8) nucleotides) identified by 32P-postlabelling were formed. No BaP metabolites or DNA adducts were observed in either control or carrier control fish. Fish sampled after 3 days /had/ 5-fold higher (P < 0.05) levels of EROD activity, a shift in the bile metabolite profile towards BaP phenol formation (1OH and 30H BaP comprising up to 60% of total metabolites detected) and the formation of two adduct spots (0.86 and 0.71 adducts/10+8 nucleotides). These results show that BaP can be metabolized and form hydrophobic DNA adducts in turbot without EROD elevation...[Telli-Karakoc F et al; Marine environmental research 54 (3-5): 511-515 (2002). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/12408610?dopt=Abstract" target=new>PubMed Abstract /AQUATIC SPECIES/ Bluegills (Lepomis macrochirus Raf.) were exposed to (14C)anthracene or (14C)benzo[a]pyrene (BaP) in water. ... The initial uptake-rate coefficient for anthracene (KU = 36 hr-1) was ... independent of exposure concentration. The presence of dissolved humics did not affect anthracene uptake but did reduce the BaP uptake rate significantly. Biotransformation of the anthracene was constant at 0.22 nmol/g/hr, with approximately 92% of the residue unmetabolized at 4 hr. Uptake of BaP was linear (KU = 49 hr-1), although biotransformation increased from 0.044 to 0.088 nmol/g/hr between 1 and 2 hr of exposure. Only 11% of the BaP 14C activity at 4 hr represented the parent compound. Although 6% of the anthracene was found in liver and gall bladder, 25% of the BaP was distributed in the two organs. Depuration rates were first order and yielded half-lives of 17 hr for anthracene and 67 hr for BaP. The estimated bioconcentration factors (BCF) for anthracene and BaP in whole fish (KU/KD) were 900 and 4900, respectively, for total 14C activity, but only 675 and 490 for parent material. These BCFs were considerably lower

than those predicted from the octanol-water partition coefficients because of biotransformation.[Spacie A et al; Ecotoxicology and Environmental Safety 7 (3): 330-341 (1983). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6307636?dopt=Abstract" target=new>PubMed Abstract /AQUATIC SPECIES/ The aim of the present work was to study the genotoxicity and the embryotoxicity of ... relevant pollutants for oyster embryos /including/ benzo[a]pyrene (BaP) ... . Gamete fertilization was performed and embryo development followed in contaminated reference seawater. Following exposure, embryotoxicity was evaluated /and/ genotoxicity was measured ... by conducting a comet assay on enzymatically dissociated cells of pre-shelled larvae (16 hr development). The oxidized DNA base, 8-oxodGuo, was also measured ... .The relationship between genotoxicity and embryotoxicity was then studied to check for the possible significance of genotoxicity in the population dynamics of marine bivalves from polluted areas. For BaP, embryotoxicity and DNA strand breakage were both observed from the lowest tested concentration of 0.2 nM. Induction of 8-oxodGuo was significant from 20 nM. ... Taking into account all the data collected during this study, a positive and significant correlation was demonstrated in oyster embryos between genotoxicity as measured by the comet assay and embryotoxicity.[Wessel N et al; Aquatic toxicology (Amsterdam, Netherlands) 85 (2): 133-142 (2007). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/17904659?dopt=Abstract" target=new>PubMed Abstract /AQUATIC SPECIES/ Dose dependent effects of benzo[a]pyrene (BaP) on cytochrome P4501A (CYP1A), glutathione-S-transferase (GST) and fluorescent aromatic compounds (FACs) metabolites biomarker responses were studied in African sharptooth catfish (Clarias gariepinus) following 24 hr of waterborne exposures. Based on biomass of C. gariepinus in different tanks, BaP concentrations of 1.60, 3.44, and 18.21 ug/L that corresponded to 0.5, 1.0, and 5.0 mg/kg body weight were used. Significant induction of EROD activities in gill filaments was observed at all doses and the accumulation of FACs metabolites in bile was significantly different between groups. Accumulation of FACs metabolites in bile strongly correlated (r (2) = 0.99) with BaP doses. Hepatic EROD activities were undetectable and no effect on GST activities was observed...[Mdegela RH et al; Ecotoxicology (London, England) 15 (8): 629-637 (2006). Available from, as of November 23,2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/17077996?dopt=Abstract" target=new>PubMed Abstract /AQUATIC SPECIES/ /Benzo(a)pyrene/ (BaP) ... was further studied to assess the interactive and temporal responses of C. gariepinus (African sharptooth catfish) on CYP1A, GST, and FACs metabolites biomarkers following exposure to either BaP alone, 17alpha-ethynylestradiol (EE(2)) alone or a combination of both compounds at concentrations of 54.17 ug/L for BaP, 51.38 ug/L for EE(2) and 54.44 ug/L for each of both compounds. Based on biomass in each tank, these concentrations corresponded to 5 mg/kg bw. While a group of six fish was sacrificed on day 0 from the control tank only, other groups of six fish were sacrificed after 1, 3, and 6 days of exposure from the control and exposed groups. Maximum induction of gill filament and hepatic EROD activities was observed after 1 day of exposure. Both EROD activities in gill filaments and liver were significantly induced by exposure to BaP alone or co-administration with EE(2). Gill filament EROD induction was significantly inhibited (50%) by co-administration of BaP and EE(2) compared to administration of BaP

alone. Levels of FACs in bile for BaP and BaP + EE(2) exposed groups were significantly different from the control at all doses and time points. A significant induction of GST activities was observed in fish exposed to BaP and BaP + EE(2) after 3 days. Exposure to EE(2) alone caused significant induction of this enzyme after day 6. This study reports ... the significant antagonistic influence of EE(2) on BaP in gills of fish following waterborne exposures. The results also indicate that chemical mixtures may affect biomarker responses differently from compounds administered alone and that the sensitivity of CYP1A to interactive chemicals is different in gills and liver.[Mdegela RH et al; Ecotoxicology (London, England) 15 (8): 629-637 (2006). Available from, as of November 23,2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/17077996?dopt=Abstract" target=new>PubMed Abstract /AQUATIC SPECIES/ ... The consequences of photo-induced toxicity are reported here for embryo-larval stages of the pacific oyster Crassostrea gigas, following exposure to pyrene and benzo[a]pyrene. During laboratory investigations, significant increases in toxicity were observed in the presence of environmentally attainable levels of UV-radiation, compared with embryos exposed to PAH alone, at levels previously deemed to have little acute biological effect. The phototoxicity of pyrene and benzo[a]pyrene completely inhibited the development to the D-shell larval stage when embryos were simultaneously exposed to 5 ug/L PAH and ultraviolet light (UVB = 6.3 +/- 0.1 uW/sq cm and UVA = 456.2 +/- 55 uW/sq cm). A linear relationship was also demonstrated for benzo[a]pyrene phototoxicity with decreasing UV light intensity.[Lyons BP et al; Marine environmental research 54 (3-5): 627-631 (2002). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/12408628?dopt=Abstract" target=new>PubMed Abstract /AQUATIC SPECIES/ Effects of a model polycyclic aromatic hydrocarbon (PAH) were compared in populations of the estuarine fish Fundulus heteroclitus indigenous to a reference site and one highly contaminated with polychlorinated biphenyls (PCBs) and other compounds. The fish population resident to the PCB-contaminated site is genetically resistant to those PCB congeners categorized as dioxin-like compounds (DLCs) that act through the aryl hydrocarbon receptor (AHR). In response to DLC exposures, these DLC-resistant fish showed poor inducibility for enzymes known to be regulated by the AHR pathway ... . Therefore, a laboratory study using the model PAH, benzo[a]pyrene (BaP), was conducted to evaluate how PAHs might affect these wild fish populations... . Following BaP treatment, the activities of two xenobiotic metabolizing enzymes and the concentrations of BaP-DNA adducts ... were lower in the livers of DLC-resistant than reference fish. These results suggest that DLC-resistance could provide protection following chronic exposures to PAHs from the long-term consequences of DNA adduct formation, such as cancer. Alternatively, reduced metabolism and elimination of toxic or photo-activated PAHs could have acute consequences to the health and reproduction of these DLC-resistant fish and their progeny.[Nacci DE et al; Aquatic toxicology (Amsterdam, Netherlands) 57 (4): 203-215 (2002). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/11932001?dopt=Abstract" target=new>PubMed Abstract /OTHER TERRESTRIAL SPECIES/ /Investigators/ examined the toxicity of benzo[a]pyrene (BaP) to several standard test organisms including the seed emergence and early life-stage growth of three terrestrial plants (Trifolium pratense, Lolium perenne, and Brassica alba), the survival and

reproduction of enchytraeids (Enchytraeus crypticus), and the nitrifying ability of soil bacteria. ... /investigators/ included a two-species reproduction test with predatory mites (Hypoaspis aculeifer) and collembolan (Folsomia fimetaria) prey. No effect or only weak effects even at very high BaP concentrations were observed for all tests... Compared to a number of other polycyclic aromatic compounds previously tested in the same soil type, BaP is generally less toxic.[Sverdrup LE et al; Ecotoxicology and Environmental Safety 66 (3): 362-368 (2007). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/16530836?dopt=Abstract" target=new>PubMed Abstract /PLANTS/ In a series of soil and hydrocultures of the higher plants, tobacco, rye, and radish, as well as algae cultures of lower plants (Chlorella vulgaris, Scenedesmus obligurus, and Ankistrodesmus) /results indicate/ that certain polycyclic aromatic hydrocarbons have growth-promoting effects on plants. Further, the degree of the promoting effect corresponded to the oncogenic activity of the hydrocarbon. The six polycyclic aromatic hydrocarbons found in plants were tested one at a time or in combination. Considerable growth-promotion was noted (near to 100% in some cases) with the effectiveness of hydrocarbons ranked as follows: (1) benzo[a]pyrene (2) benzo[a]anthracene (3) indeno [1,2,3-cd]pyrene, benzo[b]fluoranthene (4) fluoranthene (5) benzo[ghi]perylene.[Health &amp; Welfare Canada; Polycyclic Aromatic Hydrocarbons p.67 (1979) Report No. 80-EHD-50] **PEER REVIEWED** NON-HUMAN TOXICITY VALUES: LD50 Rat sc 50 mg/kg[Warshawsky D; Patty's Toxicology CD-ROM (2005). NY, NY: John Wiley &amp; Sons; Polycyclic and Heterocyclic Aromatic Hydrocarbons. Online Posting Date: April 16, 2001.] **PEER REVIEWED** LD50 Mouse ip about 250 mg/kg[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V32 213 (1983)] **PEER REVIEWED** ECOTOXICITY VALUES: LC50; Species: Neanthes arenaceodentata (annelid); Concentration: > 1.0 mg/L for 96 hr /Conditions of bioassay not specified in source examined/[Verschueren, K. Handbook of Environmental Data on Organic Chemicals. 3rd ed. New York, NY: Van Nostrand Reinhold Co., 1996., p. 302] **PEER REVIEWED** LC50; Species: Daphnia pulix (crustacean); Concentration: 0.005 mg/L for 96 hr /Conditions of bioassay not specified in source examined/[Verschueren, K. Handbook of Environmental Data on Organic Chemicals. 3rd ed. New York, NY: Van Nostrand Reinhold Co., 1996., p. 302] **PEER REVIEWED** LC50; Species: Aedes aegypti (insect); Concentration: 0.008 mg/L for 12 hr /Conditions of bioassay not specified in source examined/[Verschueren, K. Handbook of Environmental Data on Organic Chemicals. 3rd ed. New York, NY: Van Nostrand Reinhold Co., 1996., p. 302] **PEER REVIEWED** LC50; Species: Aedes aegypti (insect); Concentration: 0.002 mg/L for 36 hr /Conditions of bioassay not specified in source examined/[Verschueren, K. Handbook of Environmental Data on Organic Chemicals. 3rd ed. New York, NY: Van Nostrand Reinhold Co., 1996., p. 302] **PEER REVIEWED**

LC50; Species: Rana pipiens (amphibian); Concentration: > 6.7 mg/L for 24 hr /Conditions of bioassay not specified in source examined/[Verschueren, K. Handbook of Environmental Data on Organic Chemicals. 3rd ed. New York, NY: Van Nostrand Reinhold Co., 1996., p. 302] **PEER REVIEWED** LC50; Species: Poeciliopsis lucida (fish); Concentration: 1.2-3.7 mg/L for 24 hr /Conditions of bioassay not specified in source examined/[Verschueren, K. Handbook of Environmental Data on Organic Chemicals. 3rd ed. New York, NY: Van Nostrand Reinhold Co., 1996., p. 302] **PEER REVIEWED** EC50; Species: Pseudokirchneriella subcapitata (Green algae, 500000 cells/mL); Conditions: freshwater, static, 23 deg C; Concentration: 15 ug/L for 72 hr; Effect: growth, general /97% purity/[Schoeny R et al; Mutat Res 197 (2): 289-302 (1988) as cited in the ECOTOX database. Available from, as of August 21, 2009: http://cfpub.epa.gov/ecotox/quick_query.htm] **PEER REVIEWED** EC50; Species: Xenopus laevis (African clawed frog, embryo); Conditions: freshwater, renewal, 23 deg C; Concentration: 8700 ug/L for 96 hr (95% confidence interval: 7900-9500 ug/L); Effect: development, deformation[Propst TL et al; Drug Chem Toxicol 20 (1/2): 45-61 (1997) as cited in the ECOTOX database. Available from, as of August 21, 2009: http://cfpub.epa.gov/ecotox/quick_query.htm] **PEER REVIEWED** LC50; Species: Xenopus laevis (African clawed frog, embryo); Conditions: freshwater, renewal, 23 deg C; Concentration: 13400 ug/L for 96 hr (95% confidence interval: 12500-14300 ug/L)[Propst TL et al; Drug Chem Toxicol 20 (1/2): 45-61 (1997) as cited in the ECOTOX database. Available from, as of August 21, 2009: http://cfpub.epa.gov/ecotox/quick_query.htm] **PEER REVIEWED** EC50; Species: Daphnia magna (Water flea, about 4 days old juvenile); Conditions: freshwater, static, 20 deg C, pH 8.0, alkalinity 250 mg/L CaCO3; Concentration: 40 ug/L for 24 hr (95% confidence interval: 32-49 ug/L); Effect: intoxication, immobilization[Wernersson AS, Dave G; Arch Environ Contam Toxicol 32 (3): 268-273 (1997) as cited in the ECOTOX database. Available from, as of August 21, 2009: http://cfpub.epa.gov/ecotox/quick_query.htm] **PEER REVIEWED** LT50 (time to 50% mortality); Species: Pimephales promelas (Fathead minnow, larvae 7 days posthatch); Conditions: freshwater, renewal; Concentration: 5.6 ug/L for 40.05 hr[Oris JT Jr; Chemosphere 16 (7): 1395-1404 (1987) as cited in the ECOTOX database. Available from, as of August 21, 2009: http://cfpub.epa.gov/ecotox/quick_query.htm] **PEER REVIEWED** TSCA TEST SUBMISSIONS: The effects of subchronic benzo(a)pyrene (BaP) exposure on the resistance of B6C3F1 female mice to exposure to infectious pathogens or tumor cells were evaluated. Groups of female mice (8/group except vehicle controls, 12/group) were dosed with BaP at 0, 5, 20 or 40 mg/kg in corn oil vehicle by subcutaneous injection daily for 14 days and one control group received no BaP treatment. On day 15 the animals were challenged with a pathogen or tumor cells and observed for mortality and other toxicity signs. The effect of BaP exposure on host resistance to pathogens was as follows (pathogen/effect on resistance): Listeria monocytogenes/increased resistance, B16F10 Melanoma cells/decreased resistance, Herpes Simplex Type 2/decreased resistance, Influenza A2/no change in resistance, and

Streptococcus pneumonia/decreased resistance.[Medical College of Virginia; Effects of Subchronic Fourteen Day Exposure to Benzopyrene in B6C3F1 Female Mice on Host Resistance. (1984), EPA Document No. FYI-AX-1084-0309] **UNREVIEWED** A subcutaneous study was conducted with female B6C3F1 mice injected subcutaneously with 0, 5, 20 or 40 mg/kg benzo(a)pyrene (BaP) in corn oil vehicle daily for 14 days and then challenged with organisms or tumor cells at 4 challenge levels/BaP dose level. Subchronic exposure to BaP resulted in a BaP dose-dependent increase in protection to Listeria monocytogenes infection. Exposure to BaP caused a dose-dependent increase in the pulmonary tumor burden of mice administered B16F10 melanoma cells intravenously 1 day after the last BaP exposure. Exposure to BaP caused a decrease in resistance to Herpes Simplex Type 2 virus (not dose-dependent) and Streptococcus pneumonia (dose-dependent). There was no effect observed due to exposure to BaP on the level of protection to Influenza A2.[Medical College of Virginia; Effects of Subchronic Fourteen Day Exposure to Benzopyrene in B6C3F1 Female Mice on Host Resistance. (1985), EPA Document No. FYI-AX-0485-0220, Fiche No. OTS0000220-2] **UNREVIEWED** A subcutaneous study was conducted with male and female B6C3F1 mice (72-139/group) injected subcutaneously with 0.01 ml/g body weight of solutions in corn oil vehicle at concentrations of 0, 0.5, 2.0 or 4.0 mg/ml benzo(a)pyrene (BaP) daily for 14 days. There were significant differences between treated and control animals in the following: increased body and absolute liver weights (males at all doses), decreased absolute spleen weight (males at high-dose), decreased relative and absolute thymus weight (females at high-dose), decreased relative brain and spleen weights (both sexes, all dose levels), decreased blood levels of hemoglobin, hematocrit, leukocytes, erythrocytes, (both sexes at high-dose), and total protein and globulin levels (decreased in both sexes at high-dose and increased in low-dose males), and decreased in various serum immunoglobulin levels (high- and mid-dose females, males at all doses). There were no significant differences between treated and control animals in the following: absolute brain, kidney, and lung weights, relative liver, kidney and lung weights, blood levels of lymphocytes, neutrophils, monocytes, eosinophils, globulin, and serum complement levels.[Medical College of Virginia; Effects of Subchronic Fourteen Day Exposure to Benzopyrene in B6C3F1 Male and Female Mice on Specific Immunological Parameters, Final Report. (1985), EPA Document No. FYI-AX-1283-0220, Fiche No. OTS0000220-1] **UNREVIEWED** A subcutaneous study was conducted with male and female B6C3F1 mice (72-139/group) injected subcutaneously with 0.01 ml/g body weight of solutions in corn oil vehicle at concentrations of 0, 0.5, 2.0 or 4.0 mg/ml benzo(a)pyrene (BaP) daily for 14 days. Groups of 8-12 rats each were immunized with sheep red blood cells (SRBC) on day 10 or 11 of exposure and the humoral immune response was evaluated by measuring the spleen IgM antibody forming cells (AFC) response 1 day after the last exposure to BaP. Significant decreases were observed in the number of AFC in animals treated with BaP and SRBC when compared to solvent controls. Delayed hypersensitivity response to SRBC was suppressed in high-dose female and male animals to a level of 59% and 45% of controls, respectively. The ability of male and female mice to produce antibodies to the T-dependent antigen sheep erythrocytes was inhibited although the parameters used to measure the functional aspects of cell mediated immunity were unaltered. BaP treatment also resulted in a suppression in the bacterial lipopolysaccharide response which was more intense for females. No differences were observed between BaP treated and control animals in the following: basal serum immunoglobulin levels, serum

complement levels, delayed hypersensitivity response to Keyhole Limpet Hemocyanin, acute inflammatory response to carrageenin, and vascular clearance of rate of sheep erythrocytes. There were no dose-dependent changes in hepatic phagocytosis.[Medical College of Virginia; Effects of Subchronic Fourteen Day Exposure to Benzopyrene in B6C3F1 Male and Female Mice on Specific Immunological Parameters, Final Report. (1985), EPA Document No. FYI-AX-1283-0220, Fiche No. OTS0000220-1] **UNREVIEWED** The effects of subchronic exposure to benzo(a)pyrene (BaP) were evaluated in male Fischer 344 rats (32/exposed groups, 40 in negative control group) injected subcutaneously with BaP at dosages of 0, 2.5, 10 or 20 mg/kg (2 ml/kg of corn oil solutions of BaP) daily for 14 days. There were significant differences between treated and control animals in the following: increased absolute weights of liver (mid-dose level), spleen and lungs (all levels), increased relative weights of liver (mid- and high- doses), spleen and lungs (all levels), decreased relative thymus and kidney weights (mid-dose level), and differential and absolute count of monocytes (low-dose level). There were no significant differences between treated and control animals in the following: body weight, body weight change, relative and absolute brain weight, absolute thymus and kidney weight, and differentials and absolute counts of total leukocytes, lymphocytes, neutrophils, and eosinophils.[Medical College of Virginia; Immunotoxicity of Benzopyrenes in Fischer 344 Rats (Final Report). (1986), EPA Document No. FYI-AX-0686-0309, Fiche No. OTS0000309-2] **UNREVIEWED** The effects of subchronic exposure to benzo(a)pyrene (BaP) were evaluated in male Fischer 344 rats (32/exposed groups, 40 in negative control group) injected subcutaneously with BaP at dosages of 0, 2.5, 10 or 20 mg/kg (2 ml/kg of corn oil solutions of BaP) daily for 14 days. Groups of 10 rats each were immunized with sheep red blood cells (SRBC) on day 10 of the exposure period and the humoral immune response was evaluated by measuring the spleen IgM antibody forming cells (AFC) response 1 day after the last exposure. There were differences between treated and control animals in the following: increased spleen weight (high- and low-BaP-dose), increased IgM AFC/spleen cell and /spleen (low-dose), and decreased IgM AFC/spleen cell and /spleen (high-dose). Rats immunized with SRBC on day 12 of exposure exhibited increased spleen weight (mid-dose level), increased IgM AFC/spleen cell and /spleen (low-dose level), and increased IgM AFC/spleen cell (high-dose level). There were no changes in delayed hypersensitivity response to keyhole limpet hemocyanin or SBRC in treated animals relative to solvent controls.[Medical College of Virginia; Immunotoxicity of Benzopyrenes in Fischer 344 Rats (Final Report). (1986), EPA Document No. FYI-AX-0686-0309, Fiche No. OTS0000309-2] **UNREVIEWED** METABOLISM/PHARMACOKINETICS: METABOLISM/METABOLITES: /It was/ demonstrated that macrophages were the primary cell type in a splenic leukocyte preparation capable of metabolizing /benzo[a]pyrene/ BaP to 7,8-dihydroxy-9,10-epoxy-benzo[a]pyrene (BPDE), the reactive metabolite proposed to be the ultimate carcinogenic and immunotoxic form of BaP.[Klaassen, C.D. (ed). Casarett and Doull's Toxicology. The Basic Science of Poisons. 7th ed. New York, NY: McGraw-Hill, 2008., p. 526] **PEER REVIEWED** Human liver microsomal fractions from 13 different individuals were characterized ... . Pronounced interindividual differences in the composition of microsomal proteins in the mol wt range of 49,000-60,000

were found. Most of the variations among profiles of microsomal proteins are interindividual differences in the composition of isoenzymes of cytochrome P450. Large variations among the human liver microsomal samples were seen in benzo[a]pyrene metabolism. The results indicate the presence of 7-8 different forms of cytochrome P450 in human liver microsomes and interindividual variations seen in drug metabolism may at least in part be explained by variations in the distribution of these isoenzymes.[Ekstroem G et al; Acta Pharmacol Toxicol 50 (4): 251-60 (1982)] **PEER REVIEWED** Colonic biopsy specimens from patients with ulcerative colitis and normal subjects were studied for the ability to metabolize benzo[a]pyrene. Approx 73% of 30 colonic biopsy specimens from 7 ulcerative colitis patients could metabolize benzo[a]pyrene to oxidized products, with an average production of 11.6 nmol/mg biopsy protein. In contrast, 39% of 23 biopsy specimens from 5 normal persons showed an average metabolic activity, 2.79 nmol. Benzo[a]pyrene oxidation activity in colonic tissue from colitis patients was, on the average, fourfold greater than that in normal subjects. This study suggest that the colonic mucosa of patients with ulcerative colitis has a greater ability than that of normal subjects to oxidize such chemicals possibly to electrophiles with higher mutagenic potential.[Mayhew JW et al; Gastroenterology 85 (2): 328-34 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6305757?dopt=Abstract" target=new>PubMed Abstract Benzo[a]pyrene is metabolized to approximately 20 primary and secondary oxidized metabolites and to a variety of conjugates. Several metabolites can induce mutations, transform cells and/or bind to cellular macromolecules; however only a 7,8-diol-9,10-epoxide is presently considered to be an ultimate carcinogenic metabolite.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V32 215 (1983)] **PEER REVIEWED** /Polycyclic aromatic hydrocarbons/ (PAHs) are metabolized by phase I enzymes and peroxidases, which produce DNA-reactive metabolites, and phase II enzymes, which form polar conjugates. Phase I enzymes, such as cytochrome P450s (CYPs), catalyse the mono-oxygenation of PAHs to form phenols and epoxides. Specific cytochrome P450 isozymes and epoxide hydrolase can form reactive diol epoxides that comprise one class of ultimate carcinogenic metabolites of many PAHs. Both cytochrome P450s and peroxidases can form radical cations by one-electron oxidation that comprise another class of ultimate carcinogenic metabolites. Further oxidation of PAH phenols leads to the formation of PAH quinones. The major cytochrome P450s that are involved in the formation of diol epoxides are CYP1A1, CYP1A2 and CYP1B1, while CYP2C9 and CPY3A4 play a minor role in the activation of PAHs. PAHs induce increased expression of activating cytochrome P450s via enhanced aryl hydrocarbon receptor mediated transcription. Polymorphisms in human cytochrome P450s have been identified, some of which may be associated with increased susceptibility. Additional enzymes that may play a role in the further activation of some PAH diols include members of the aldo-keto reductase (AKR1) family, among which polymorphisms that influence susceptibility have been identified. NAD(P)H quinone oxidoreductase 1 catalyses the reduction of PAH quinones to hydroquinones which may be re-oxidized and generate reactive oxygen species. Polymorphisms in this gene have also been described. /PAHs/[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Industrial Exposures, v 92 (2005). Summary available from, as of

November 29, 2009: http://monographs.iarc.fr/ENG/Meetings/index1.php] **PEER REVIEWED** The mechanism of meso-region biomethylation and benzylic oxidation features biomethylation of parent /polycyclic aromatic hydrocarbons/ (PAHs) to methyl PAHs. Methyl PAHs are further metabolized by cytochrome P450s to hydroxymethyl PAHs that are converted into reactive sulfate ester forms which are capable of forming DNA adducts. Studies on this mechanism have been limited to subcutaneous tissues in rats that are susceptible to PAH tumorigenesis. /PAHs/[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Industrial Exposures, v 92 (2005). Summary available from, as of November 29, 2009: http://monographs.iarc.fr/ENG/Meetings/index1.php] **PEER REVIEWED** The types and relative amounts of conjugated and nonconjugated metabolites of BaP were similar in bile of Sprague-Dawley rats and hamsters. Smaller amounts of glucuronides and larger amounts of sulfate conjugates were detected in bile of Gunn rats than in bile of Sprague-Dawley rats or hamsters. Metabolites in bile of guinea pigs were markedly different from those in the other species in that approximately 90% of the metabolites were thioether conjugates. ...[Weyland EH, Bevan DR; Am Soc Pharm Exp Ther 15 (4): 442 (1987)] **PEER REVIEWED** Eleven female C57BL/6J mice were painted with 100 ug of (3H)-benzo[a]pyrene. The mice were killed after 24 hr and the epidermal cells were isolated and homogenized. DNA, RNA, and protein fractions were isolated. The bound BaP metabolites (benzo[a]pyrene diol epoxide anti (1) and benzo[a]pyrene diol epoxide syn (2)) per mg of each polymer varied more than 50 fold with protein having the highest specific activity and DNA the lowest. Percentages of total tetraols related to the epoxides obtained by acid hydrolysis of the adducts formed in mouse skin were: protein 39% from 1, 61% from 2; RNA 21% from 1, 76% from 2; DNA 12% from 1, 88% from 2.[Koreeda M et al; Science 199: 778-81 (1978)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/622566?dopt=Abstract" target=new>PubMed Abstract In PLHC-1 hepatoma cells, benzo[a]pyrene (BaP) caused a maximum induction of cytochrome P4501A (CYP1A) activity, measured as ethoxyresorufin O-deethylation (EROD), after 4 to 8 hr of exposure, depending on the BaP concentration. The decline of EROD activity at longer exposure times was probably caused by the rapid metabolism of BaP in this system (57% metabolism within 4 hr incubation). In subsequent experiments, PLHC-1 cells were preinduced with PCB 126 for 24 hr and then received a dose of 10, 100, or 1,000 nM 3H-BaP. A 1-nM concentration of PCB 126 caused an 80-fold induction of CYP1A activity, resulting in an increase in BaP metabolism of less than 10%, except at the highest concentration of BaP (1,000 nM), where a 50% increase was observed. In another experiment, an 80-fold induction of CYP1A activity caused a 20% increase in the metabolism of BaP (100 nM), and RNA adduct formation was increased approximately twofold. These results indicate that, at exposure concentrations up to 100 nM BaP, CYP1A activity is not rate limiting for BaP metabolism. Furthermore, CYP1A seems to also be specifically involved in BaP activation in PLHC-1 cells. However, CYP1A induction causes only a relatively small increase in activation, probably because of the action of other enzymes involved in BaP activation and deactivation.[Smeet JMW et al; Environ Toxicol Chem 18 (3): 474-80 (1999)] **PEER REVIEWED** The metabolism of benzo[a]pyrene [BP], a model carcinogenic PAH, by

hepatic microsomes of two duck species, mallard (Anas platyrhynchos) and common merganser (Mergus merganser americanus) collected from chemically-contaminated and relatively non-contaminated areas was investigated. The rate of metabolism of BP by liver microsomes of common merganser and mallard collected from polluted areas (2,650 +/- 310 and 2,200 +/- 310 pmol/min per mg microsomal protein, respectively) was significantly higher than that obtained with liver microsomes of the two species collected from non-polluted areas (334 +/- 33 and 231 +/- 30 pmol/min per mg microsomal protein, respectively). The level of cytochrome P-450 1A1 was significantly higher in the liver microsomes of both duck species from the polluted areas as compared to the ducks from the non-polluted areas. The major BP metabolites, including BP-9, 10-diol, BP-4, 5-diol, BP-7, 8-diol, BP-1, 6-dione, BP-3, 6-dione, BP-6, 12-dione, 9-hydroxy-BP and 3-hydroxy-BP, formed by liver microsomes of both duck species from polluted and non-polluted areas, were qualitatively similar. However, the patterns of these metabolites were considerably different from each other. Liver microsomes of ducks from the polluted areas produced a higher proportion of benzo-ring dihydrodiols than the liver microsomes of ducks from the non-polluted areas, which converted a greater proportion of BP to BP-phenols. The predominant enantiomer of BP-7,8-diol formed by hepatic microsomes of the two duck species had an (-)R,R absolute stereochemistry. The data suggest that duck and rat liver microsomal enzymes have different regioselectivity but similar stereoselectivity in the metabolism of BP.[Honey S et al; Comparative biochemistry and physiology. Toxicology &amp; Pharmacology: CBP 126 (3): 285-292 (2000). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/11048678?dopt=Abstract" target=new>PubMed Abstract ...The relatively insensitive channel catfish 1) do not produce mutagenic PAH metabolites, and/or 2) they more quickly eliminate PAHs due to greater Phase II enzyme activities than the more sensitive brown bullhead. Livers and bile were collected from each species 6, 24, 72, and 168 hr after a single 10 mg/kg ip benzo[a]pyrene (BaP) exposure. BaP treatment had no significant effect on cytosolic 1-chloro-2,4-dinitrobenzene or ethacrynic acid (EA)-glutathione-S:- transferase (GST) and cis-stilbene oxide-microsomal epoxide hydrolase (EH) activities of either species. Channel catfish EH and GST activities were 1.2-fold higher than brown bullhead activities (p = 0.058 and p < 0.002, respectively). HPLC-APCI-MS of extracted bile and bile enzymatically digested to detect glucuronyl transferase (GT), GST, and sulfotransferase (ST) conjugated metabolites indicated no species differences in elimination or profiles of total biliary metabolites. GT conjugates predominated; ST and GST conjugates were minimal. BaP-diones accounted for the majority of metabolites in both species. Overall, these results indicated that brown bullhead preferentially formed BaP-7,8-dihydrodiol, a precursor to the DNA-reactive BaP-7, 8-dihydrodiol-9,10-epoxide (BPDE), which may be linked to the increased PAH susceptibility in this species.[Willett KL et al; Toxicological Sciences: an official journal of the Society of Toxicology 58 (1): 68-76 (2000). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/11053542?dopt=Abstract" target=new>PubMed Abstract Juvenile rainbow trout (Oncorhynchus mykiss) were fasted or fed one of three isoenergetic diets varying in protein and lipid content at full satiation levels or half rations for up to 9 weeks. At 3, 6, and 9 weeks, fish in each treatment group were dosed intraperitoneally with 10 mg tritiated benzo[a]pyrene (3H)-B[a]P/kg (BaP) to examine the effects of

diet composition and energy intake on xenobiotic biotransformation and excretion. The percent dose eliminated during the experiment did not differ among fish receiving the different diet compositions or rations (range 73% to 84%). However, it was significantly decreased (to 53%) in the group that was fasted for 9 weeks. Examination of fish fasted for 6 and 9 weeks showed a significant increase in the proportion of phase I metabolites and a concomitant decrease in the proportion of phase II metabolites found in bile compared with all other groups. Also, fish that were fasted for 9 weeks produced proportionately less 9,10-dihydroxy-benzo[a]pyrene-trans-9,10-diol, more 3-hydroxybenzo[a]pyrene and 9-hydroxybenzo[a]pyrene, and more glucuronic acid conjugates compared with all other groups. Thus, dietary protein and lipid concentration did not appear to affect either the rate of B[a]P metabolism or its excretion; however, prolonged fasting resulted in a shift in metabolite profiles and decreased excretion.[Kennedy CJ et al; Archives of environmental contamination and toxicology 47 (3): 379-386 (2004). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/15386132?dopt=Abstract" target=new>PubMed Abstract Microsomes were isolated from the liver and testes of rat, mouse, hamster, ram, boar, bull, and monkey and incubated with BaP. Post-incubation, samples were extracted with ethyl acetate and analyzed for BaP/metabolites by reverse-phase HPLC with fluorescence detection. A great variation among species to metabolize BaP was observed. The rodent testicular microsomes produced higher proportions of BaP 4,5-diol and 9,10-diol than did boar, ram, bull, and monkey. On the other hand, hepatic microsomes from higher mammals converted a greater proportion of BaP to 3-hydroxy and 9-hydroxy BaP, the detoxification products of BaP...[Smith TL et al; Toxicology in vitro: An International Journal Published in Association with BIBRA 21 (4): 753-758 (2007). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/17317092?dopt=Abstract" target=new>PubMed Abstract ABSORPTION, DISTRIBUTION & EXCRETION: ... Readily absorbed from the intestinal tract and tend to localize primarily in body fat and fatty tissues such as breast. Disappearance of Benzo(a)Pyrene from blood and liver of rats following single IV injection is very rapid, having a half-life in blood of less than 5 min and a half-life in liver of 10 min. In ... blood and liver ... initial rapid elimination phase is followed by slower disappearance phase, lasting 6 hr or more ... A rapid equilibrium is established between BaP in blood and that in liver and ... the cmpd fast disappearance from blood is due to ... metabolism and distribution in tissues.[National Research Council. Drinking Water &amp; Health, Volume 4. Washington, DC: National Academy Press, 1981., p. 257] **PEER REVIEWED** BaP crosses the placenta in mice &amp; rats ... .[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V32 214 (1983)] **PEER REVIEWED** (14)C metabolites were secreted into bile of rats within 7 min of iv dose of (14)C-benzo[a]pyrene. Pretreatment of animals with this carcinogen ... enhanced biliary secretion of (14)C.[The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 2: A Review of the Literature Published Between 1970 and 1971. London: The Chemical Society, 1972., p. 153] **PEER REVIEWED**

Male rats cannulated in the bile duct received iv injections of radiolabeled benzo[a]pyrene (BaP)noncovalently bound to the very-low-density, low-density, or high-density lipoproteins in equimolar amounts. Cumulative biliary excretions of BaP complexed with rat lipoproteins were 39.6, 24.6, and 21.2% for very-low density, low-density, and high-density lipoprotein, respectively. Values for excretion of BaP complexed with rat or human lipoproteins were comparable. Excretion increased as the degree of BaP hydroxylation increased. The excretion of BaP bound to very-low-density, low-density, or high-density lipoproteins in Aroclor-induced rats was not greater than the control. Hence, 60-80% of injected BaP and 50-60% of injected BaP metabolites were not excreted immediately in control or induced animals. This BaP may represent a carcinogen pool that is slowly excreted.[Shu HP, Bymun EN; Cancer Res 43 (2): 485-90 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6293698?dopt=Abstract" target=new>PubMed Abstract Benzo[a]pyrene (BaP), a lipophilic promutagen, reached maximal concentrations in the thoracic duct lymphatic circulation within 2 hr after gastric instillation. BaP in lymph obtained by thoracic duct cannulation /in female sheep/ decreased to approximately control levels within 4 hr after treatment. When lymph was not allowed to enter the blood vascular circulation, serum levels of BaP increased very slowly, suggesting minimal mesenteric blood vascular absorption of the lipophilic hydrocarbon. BaP partitions into lymph lipoproteins as a function of the lipoprotein concentration. Data suggest that low-density lipoproteins may take up BaP more efficiently than do very low-density or high-density lipoproteins, and that lymph components other than lipoproteins do not take up and transport BaP. The authors propose that lipophilic xenobiotic compounds interact with cells of the immune system via lymphatic lipoprotein transport of potentially mutagenic, carcinogenic, or immunosuppressive agents.[Busbee DL et al; J Toxicol Environ Health 13 (1): 43-51 (1984)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6325719?dopt=Abstract" target=new>PubMed Abstract Comparison of disposition of benzo(a)pyrene (BaP) among Sprague-Dawley rats, Gunn rats, hamsters, and guinea pigs was performed. BaP was administered intratracheally to animals, and the rate of excretion of radioactivity into bile, types of metabolites of BaP in bile, and distribution of radioactivity were qualitatively similar among these species although quantitative differences were observed. In hamsters, the rate of excretion was essentially independent of dose at the concentrations examined (0.16 and 350 ug). The major difference between hamsters and the other species was that increased amounts of radioactivity were retained in lung of hamsters at the lower dose with a proportional decrease in the amount of radioactivity excreted into bile.[Weyland EH, Bevan DR; Am Soc Pharm Exp Ther 15 (4): 442 (1987)] **PEER REVIEWED** In an attempt to understand route of administration dependency, 3H-benzo[a]pyrene, (14)C-urethane and (14)C-acrylamide were administered as single doses orally or topically to male SENCAR mice. Distribution in skin, stomach, liver, and lung was determined for time periods up to 48 hr. The binding of these compounds to DNA, RNA, and protein in these tissues was determined 6 and 48 hr after administration. For all three compounds, high concentrations were found in the skin following topical application, but very little material reached this target organ following oral administration. The internal organs generally contained more material after oral administration compared to topical application, whereas the

opposite was true for the skin. Differences in distribution to the skin and binding to macromolecules following oral or topical administration cannot explain the greater tumorigenicity of urethane and acrylamide after oral administration in the SENCAR mouse.[Carlson GP et al; Environ Health Perspect 68: 53-60 (1986)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/3780633?dopt=Abstract" target=new>PubMed Abstract Serum was taken from fasting, male Sprague-Dawley rats and the uptake of (14)C-benzo[a]pyrene (BaP) and subsequent extraction of bound BaP was determined by radio-scintillation techniques. The initial uptake velocity for BaP was similar to human serum for all concentrations of BaP used. Maximum uptake of BaP was estimated at 120 ug/mL for rat serum. In rat serum, low-density lipoproteins contained 50% of the bound BaP, highdensity lipoproteins contained 40%, and albumin contained 10% of the total BaP added. In rat serum, the HDL component contained 40-50% of BaP, and the LDL component contained 19-22% of the added BaP. After removal of the lipoproteins from the serum, bound BaP was associated entirely with albumin.[Aaarstad K et al; Toxicology 47 (3): 235-45 (1987)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/3424381?dopt=Abstract" target=new>PubMed Abstract The influence of maternal binding of benzo[a]pyrene (BaP) on its disposition into fetal tissue was investigated in pregnant Swiss-Webster mice. Low doses (10 ng/mouse) of radiolabeled benzo(a)pyrene were administered by intravenous injection on day 15 of gestation. BaP was administered along with normal rabbit serum (NRS) (low binding paradigm) or anti-benzo(a)pyrene antiserum (high binding paradigm) and animals killed at various time points. Total radioactivity in the fetus increased with time to peak concentrations in whole fetal homogenates at 12 hours. In contrast, maternal serum, liver, and lung showed a decrease in total radioactivity over the same time period. Total radioactivity/gram of fetal tissue was significantly higher in NRS-treated animal 5 compared to anti-BaP-antiserum-treated animals. Since the levels of the parent compound, BaP, in fetal tissue fell over time similar to maternal liver and lung, the increase in total radioactivity in the fetus was due to an increased concentration of a BaP metabolite fraction in both the low binding and high binding groups. Significantly, a lower level of this metabolite fraction was found in fetal tissue from the anti-BaP-antiserum-treated animals. The present study shows that maternal exposure to this environmental pollutant, even at low doses, results in an accumulation of a metabolite-rich fraction in the fetal compartment, which may contribute to the teratogenic potential of BaP. The data also demonstrate that the amount of this accumulation can be diminished by increasing maternal binding proteins, such as by treatment with anti-BaP antiserum.[McCabe DP, Flynn EJ; Teratology 41 (1): 85-95 (1990)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/2305376?dopt=Abstract" target=new>PubMed Abstract The maternal-fetal exchange of the tobacco related carcinogen, benzo[a]pyrene (BP), was studied in women smokers during pregnancy. The number of cigarettes smoked per day by each of the women in the study was assessed via questionnaire and by measurement by immunoassay of serum and urine cotinine in maternal and fetal blood samples. Maternal and fetal blood samples were classified as coming from nonsmokers (n = 74), individuals smoking less than 1 pack of cigarettes per day (n = 16), individuals smoking 1 pack of cigarettes per day (n = 19), individuals smoking 1-2 packs of cigarettes per day (n = 19), and individuals smoking

greater than 2 packs of cigarettes per day (n = 20). Both maternal and fetal blood samples were obtained at the time of delivery. ... Background levels of benzo[a]pyrene - Hb adducts were detected in maternal nonsmokers (6.83 + or - 3.46 pmol BP tetrol/g Hb, mean + or - SD) and in fetal samples (3.46 + or - 1.81 pmol/g Hb). Increasing levels of benzo[a]pyrene - Hb adducts were found as the smoking status of the women increased ranging from (8.93 + or - 5.21 (less than 1 pack per day) to 96.75 + or 18.66 (greater than 2 packs per day). A corresponding increase in the presence of fetal benzo[a]pyrene Hb adducts was also detected (10.31 + or - 3.11; less than 1 pack/day to 52.55 + or - 14.26; greater than 2 packs/day). This study confirms that the tobacco related carcinogen, benzo[a]pyrene, crosses the human placenta and binds to fetal Hb in significantly higher concentrations in smokers when compared to nonsmokers.[Spinnato JA et al; Toxicologist 30(1 Pt 2): 238 (1996)] **PEER REVIEWED** Serum was taken from male human subjects (age 20-40 years) and the uptake /during in vitro incubation/ of (14)C-benzo[a]pyrene (BaP) and subsequent extraction of bound BaP was determined by radio-scintillation techniques. The initial uptake velocity for BaP by human (60 ug/mL x hr) was similar to that of rat serum for all concentrations of BaP used. Maximum uptake of BaP was estimated at 230 ug/mL for human serum. Gel filtration of human serum containing (14)C-BaP revealed that 80% was associated with low-density lipoproteins (LDL), 15% with high-density lipoproteins (HDL), and 5% with albumin. BaP binding at concentrations up to and including 50 ug BaP/mL was not saturable. In human serum the highest amount of bound BaP was associated with LDL (44-47%) and HDL (32-35%) components.[Aarstad K et al; Toxicology 47 (3): 235-45 (1987)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/3424381?dopt=Abstract" target=new>PubMed Abstract BIOLOGICAL HALF-LIFE: ... /In mice/ hydrocarbon/deoxyribonucleoside adduct showed approx parallel dose-response curves. The half-life of the BaP/deoxyribonucleoside adducts and the total radioactivity bound to the DNA were 4.5 and 5.5 days ...[Ashurst SW et al; Cancer Res 43 (3): 1024-9 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6297716?dopt=Abstract" target=new>PubMed Abstract Disappearance of Benzo(a)Pyrene from blood and liver of rats following single iv injection is very rapid, having a half-life in blood of less than 5 min and a half-life in liver of 10 min.[National Research Council. Drinking Water &amp; Health, Volume 4. Washington, DC: National Academy Press, 1981., p. 257] **PEER REVIEWED** The half-life of the Benzo(a)Pyrene/deoxyribonucleoside adducts and the total radioactivity bound to the DNA were 4.5 and 5.5 days, respectively.[Ashurst SW et al; Cancer Res 43 (3): 1024-9 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6297716?dopt=Abstract" target=new>PubMed Abstract MECHANISM OF ACTION: The complete sequence of steps in the metabolic activation pathway of benzo[a]pyrene to mutagenic and carcinogenic diol epoxides has been demonstrated in experimental animals, in human tissues and in humans. Following exposure, humans metabolically activate benzo[a]pyrene to benzo[a]pyrene diol epoxides that form DNA adducts: the anti-benzo[a]-pyrene-7,8-diol-9,10-oxide.deoxyguanosine adduct has been

measured in populations (eg, coke-oven workers, chimney sweeps) exposed to PAH mixtures that contain benzo[a]pyrene. The reactive anti-benzo[a]pyrene-7,8-diol-9,10-oxide induces mutations in rodent and human cells. Mutations (G to T transversions) in the K-Ras proto-oncogene in lung tumours from benzo[a]pyrene-treated mice are associated with anti-benzo[a]pyrene-7,8-diol-9,10-oxide. deoxyguanosine adducts. Similar mutations in the K-RAS proto-oncogene and mutations in TP53 were found in lung tumors from nonsmokers exposed to PAH-rich coal combustion products that are known to contain benzo[a]pyrene (as well as many other PAHs). In an in-vitro study, the codons in the tumor-suppressor gene TP53 that are most frequently mutated in human lung cancer were shown to be targets for DNA adduct formation and mutations induced by benzo[a]pyrene.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Industrial Exposures, v 92 (2005). Summary available from, as of November 29, 2009: http://monographs.iarc.fr/ENG/Meetings/index1.php] **PEER REVIEWED** /Polycyclic aromatic hydrocarbons/ (PAHs) are metabolized by phase I enzymes and peroxidases, which produce DNA-reactive metabolites, and phase II enzymes, which form polar conjugates. Phase I enzymes, such as cytochrome P450s (CYPs), catalyse the mono-oxygenation of PAHs to form phenols and epoxides. Specific cytochrome P450 isozymes and epoxide hydrolase can form reactive diol epoxides that comprise one class of ultimate carcinogenic metabolites of many PAHs. Both cytochrome P450s and peroxidases can form radical cations by one-electron oxidation that comprise another class of ultimate carcinogenic metabolites. Further oxidation of PAH phenols leads to the formation of PAH quinones. The major cytochrome P450s that are involved in the formation of diol epoxides are CYP1A1, CYP1A2 and CYP1B1, while CYP2C9 and CPY3A4 play a minor role in the activation of PAHs. PAHs induce increased expression of activating cytochrome P450s via enhanced aryl hydrocarbon receptor mediated transcription. Polymorphisms in human cytochrome P450s have been identified, some of which may be associated with increased susceptibility. Additional enzymes that may play a role in the further activation of some PAH diols include members of the aldo-keto reductase (AKR1) family, among which polymorphisms that influence susceptibility have been identified. NAD(P)H quinone oxidoreductase 1 catalyses the reduction of PAH quinones to hydroquinones which may be re-oxidized and generate reactive oxygen species. Polymorphisms in this gene have also been described. /PAHs/[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Industrial Exposures, v 92 (2005). Summary available from, as of November 29, 2009: http://monographs.iarc.fr/ENG/Meetings/index1.php] **PEER REVIEWED** The current understanding of the carcinogenesis of /polycyclic aromatic hydrocarbons/ (PAHs) in experimental animals is almost solely based on two complementary mechanisms: those of the diol epoxide and the radical cation. Each provides a different explanation for the data observed in experimental animals. The diol epoxide mechanism features a sequence of metabolic transformations of PAHs, each of which leads to potentially reactive genotoxic forms. In general, PAHs are converted to oxides and dihydrodiols, which are in turn oxidized to diol epoxides. Both oxides and diol epoxides are ultimate DNA-reactive metabolites. PAH oxides can form stable DNA adducts and diol epoxides can form stable and depurinating adducts with DNA through electrophilic carbonium ions. The inherent reactivities of oxides and diol epoxides are dependent on topology (e.g. bay regions, fjord regions, cyclopenta rings), and the reactivity of diol epoxides is further dependent on factors such as stereochemistry and

degree of planarity. Both stable and depurinating adducts are formed primarily with guanines and adenines, and induce mutations (e.g. in ras proto-oncogenes) that are strongly associated with the tumorigenic process. Some mutagenic PAH diols, oxides and diol epoxides are tumorigenic in experimental animals. One-electron oxidation creates radical cations at a specific position on some PAHs. The ease of formation and relative stabilities of radical cations are related to the ionization potential of the PAH. Additional important factors in the radical cation mechanism are localization of charge in the PAH radical cation and optimal geometric configuration, particularly the presence of an angular ring. The radical cation mechanism results in the formation of depurinating DNA adducts with guanines and adenines, which generate apurinic sites that can induce mutations in ras proto-oncogenes, which are strongly associated with tumorigenesis. /PAHs/[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Industrial Exposures, v 92 (2005). Summary available from, as of November 29, 2009: http://monographs.iarc.fr/ENG/Meetings/index1.php] **PEER REVIEWED** Other mechanisms of carcinogenesis have been proposed for PAHs, but these are less well developed. The ortho-quinone/reactive oxygen species mechanism features enzymatic oxidation of non-K-region PAH diols to ortho-quinones by aldo-keto reductases, and has been studied only in in-vitro systems. These PAH ortho-quinones are highly reactive towards DNA; they yield DNA adducts and damage DNA. PAH ortho-quinones induce mutations in the p53 tumour-suppressor gene in vitro; they can also undergo repetitive redox cycling and generate reactive oxygen species, which have been associated with oxidative DNA base damage as well as the induction of pro-oxidant signals that may have consequences on growth. Reactive oxygen species can also be produced by other mechanisms such as the formation of PAH-quinones through peroxidase reactions. Thus, this pathway has the potential to contribute to the complete carcinogenicity of a parent PAH. /PAHs/[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Industrial Exposures, v 92 (2005). Summary available from, as of November 29, 2009: http://monographs.iarc.fr/ENG/Meetings/index1.php] **PEER REVIEWED** Several of the biological effects of PAHs, such as enzyme induction of xenobiotic metabolizing enzymes, immunosuppression, teratogenicity and carcinogenicity, are thought to be mediated by activating the aryl hydrocarbon receptor (AhR). This receptor is widely distributed and has been detected in most cells and tissues. There is also evidence that the AhR acts through a variety of pathways and, more recently, that cross-talk with other nuclear receptors enables cell type-specific and tissue-specific control of gene expression. Translocation of the activated AhR to the nucleus may require threshold concentrations of the ligand. Various oxidative and electrophilic PAH metabolites are also known to induce enzyme systems via anti-oxidant receptor elements. Biological effects of AhR and anti-oxidant receptor element signalling involve a variety of cellular responses, including regulation of phase I and II metabolism, lipid peroxidation, production of arachidonic acid-reactive metabolites, decreased levels of serum thyroxine and vitamin A and persistent activation of the thyroid hormone receptor. AhR signalling may result in adaptive and toxic responses or perturbations of endogenous pathways. Furthermore, metabolic activation of PAHs produces cellular stress. This in turn activates mitogen-mediated protein kinase (MAPK) pathways, notably of Nrf2. The Nrf2 protein dimerizes with Maf-oncoproteins to enable binding to an anti-oxidant/electrophilic response element, which has been identified in many phase I/II and other

cellular defence enzymes and controls their expression. Therefore, cellular stress may be regulated independently of AhR-mediated xenobiotic metabolizing enzymes. /PAHs/[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Industrial Exposures, v 92 (2005). Summary available from, as of November 29, 2009: http://monographs.iarc.fr/ENG/Meetings/index1.php] **PEER REVIEWED** Several metabolites /of BaP/ can induce mutations, transform cells and/or bind to cellular macromolecules; however, only a 7,8-diol-9,10-epoxide is presently considered to be an ultimate carcinogenic metabolite.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V32 215 (1983)] **PEER REVIEWED** ... Numerous carcinogens of electrophilic reactant type ... bind to DNA ... with ... BaP, through its activated form, 7,8-dihydrodiol-9,10-epoxide, /alkylation/ reaction is thru 10 carbon...to the 2-amino position in guanylic acid. In addn, there are minor interactions with other purines and pyrimidines...[Doull, J., C.D. Klaassen, and M. D. Amdur (eds.). Casarett and Doull's Toxicology. 2nd ed. New York: Macmillan Publishing Co., 1980., p. 114] **PEER REVIEWED** ... Benzo(a)pyrene (BaP), leads to covalent DNA modifications and the deregulation of gene expression. To date, these mechanisms of BaP-induced carcinogenesis are poorly understood, particularly in the case of breast cancer. We tested the effects of BaP exposure on cellular growth dynamics and DNA methylation in four breast cancer cell lines since disruptions in DNA methylation lead to deregulated gene expression and the loss of genomic integrity. ...robust time- and concentration-dependent loss of proliferation, S phase and G2M accumulation and apoptosis /were observed/ in p53 positive MCF-7 and T47-D cells. We observed minimal responses in p53 negative HCC-1086 and MDA MB 231 cells. Furthermore, BaP increased p53 levels in both p53 positive cell lines, as well as p21 levels in MCF-7 cells, an effect that was prevented by the p53-specific inhibitor pifithrin-alpha. No changes in global levels of DNA methylation levels induced by BaP were detected by the methyl acceptor assay (MAA) in any cell line, however, methylation profiling by AIMS (amplification of intermethylated sites) analysis showed dynamic, sequence-specific hypoand hypermethylation events in all cell lines. ... BaP-induced hypomethylation events /were observed/ at a number of genomic repeats. /The/ data confirm the p53-specific disruption of the cell cycle as well as the disruption of DNA methylation as a consequence of BaP treatment, thus reinforcing the link between environmental exposures, DNA methylation and breast cancer.[Sadikovic B, Rodenhiser DI; Toxicology and Applied Pharmacology 216 (3): 458-468 (2006). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/16926039?dopt=Abstract" target=new>PubMed Abstract CDKN2A, 9p21, encodes two alternatively spiked, functionally distinct, tumor-suppressor proteins, P16INK4A and P14ARF, which play active roles in the RB1 and TP53 pathways, respectively. Deletion of 9p is one of the most frequent genomic alterations in bladder cancer. In addition, alterations of 9p21 and P16 are frequently seen in the epithelial cells of chronic smokers. This pilot study evaluated whether 9p21 aberrations induced by exposure in vitro to benzo[a]pyrene diol epoxide (BPDE), the metabolic product of benzo[a]pyrene, a constituent of tobacco smoke, were more common in the peripheral blood lymphocytes of 61 bladder cancer patients

compared to 64 matched controls. /The authors hypothesize/ that 9p21 sensitivity to BPDE reflects the susceptibility of a specific locus to damage from carcinogens in tobacco smoke. /Investigators/ found that BPDE-induced chromosome band 9p21 aberrations were significantly higher in lymphocytes of bladder cancer cases (24.97 +/- 5.26 per 1,000) than in controls (20.72 +/- 4.51 per 1,000; P < 0.0001). However, no difference was observed for CEP9, a control locus. After adjustment for age, sex, ethnicity, and smoking status, 9p BPDE sensitivity had an odds ratio (OR) of 9.01 [95% confidence interval (95% CI) 3.75, 21.67] for bladder cancer. /Investigators/ further observed a gradient of elevated bladder cancer risk associated with increasing chromosomal damage. The adjusted ORs for subjects in the second, third, and highest quartiles of BPDE-induced 9p21 aberrations relative to the first quartile were 0.48 (0.04, 5.69), 5.14 (1.12, 23.59), and 21.51 (4.75, 97.34), respectively, providing increasing dose-response evidence of the locus-specific alterations. Thus, 9p21 may be a molecular target for BPDE-induced damage in bladder cancer cases.[Hazra, A et al; Genes, Chromosomes &amp; Cancer 41 (4): 330-338 (2004). Available from, as of November 23,2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/15390186?dopt=Abstract" target=new>PubMed Abstract ... To investigate the mechanisms of tumor inhibition, lung tissues were obtained at 21, 84, and 140 days at interim sacrifices during the bioassay. These tissues showed a significant increase in apoptosis as determined by in situ end-labeling for both ITC-NAC-treated groups. The MAP kinase pathway was activated in the ITC-NAC-treated groups. The activation of c-Jun NH(2)-terminal kinase was higher in the BITC-NAC and PEITC-NAC groups when compared with BaP-treated control. The phosphorylation of p38 and extracellular signal-regulated kinases (ErKs) 1 and 2 was also induced by these treatments. To determine the downstream target of MAP kinases, activator protein-1 (AP-1) and nuclear factor-kappaB activities were evaluated by gel shift assay. The AP-1 binding activity was remarkably increased in lung tissue from both the BITC-NAC and PEITC-NAC groups. No change in nuclear factor-kappaB binding activity was found, however. Phosphorylation of p53 was also higher than the constitutive levels in both ITC-NAC-treated groups, but no induction of p53 expression was detected. This study demonstrates the chemopreventive efficacy of the NAC conjugates of PEITC and BITC administered in the diet after a single dose of BaP for lung tumorigenesis and provides the first in vivo evidence that activation of MAP kinases, AP-1 transcription factors, p53 phosphorylation, and the induction of apoptosis may be involved in the chemopreventive activity of these compounds.[Yang YM et al; Cancer research 62 (1): 2-7 (2002). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/11782348?dopt=Abstract" target=new>PubMed Abstract Exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs) has been implicated in the aetiology of atherosclerosis. Previously we showed that chronic exposure of ApoE-/- mice to the prototype PAH benzo[a]pyrene (BaP) causes enhanced progression of atherosclerosis, which was characterised by an increased inflammatory cell content in the atherosclerotic plaques. The aim of the present study was to evaluate the effect of BaP on vascular expression of monocyte-chemoattractant protein 1 (MCP-1), which is a crucial molecule promoting the recruitment of monocytes into atherosclerotic lesions. /It was/ hypothesised that BaP-induced expression of MCP-1 is mediated through aryl hydrocarbon receptor (AhR) activation. Initially we performed in vivo studies showing that acute treatment with BaP induces MCP-1 gene expression in aortic tissue of ApoE-/- mice. These observations could be confirmed by in vitro studies with human endothelial

cells (RF24 cell line and primary HUVEC), showing a dose- and time-dependent increase in MCP-1 expression upon exposure to B[a]P. This was paralleled by an induction of cytochrome P450 1A1 and 1B1, indicating Ah receptor activation. No increased gene expression (MCP-1, CYP1A1 and 1B1) was found upon incubation with the structural isomer benzo[e]pyrene, which is a weak AhR agonist. Moreover, B[a]P-induced MCP-1 gene and protein expression was inhibited by co-treatment with the AhR antagonist alpha-naphthoflavone. In addition to its effect on basal gene expression, ...t BaP significantly enhanced TNFalpha-induced expression of MCP-1. /The authors/ were unable to block BaP-induced MCP-1 expression by antioxidant treatment. In contrast, ... addition of N-acetylcysteine or vitamin C enhanced transcription of MCP-1 by BaP. ... /These/ studies revealed potent vascular pro-inflammatory effects of BaP, as evidenced by AhR-mediated induction of MCP-1. These observations further contribute to the concept that induction of inflammation is a crucial process in PAH-enhanced atherogenesis.[Knaapen AM et al; Mutation research 621 (1-2): 31-41 (2007). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/17376491?dopt=Abstract" target=new>PubMed Abstract Nuclear factor of activated T cell (NFAT)-3 is a member of the transcription factor NFAT family, which has been demonstrated to be responsible for the up-regulation of the pro-inflammatory cytokine tumor necrosis factor (TNF) in the immune system. Our most recent studies have also shown that TNF is able to induce cell transformation in mouse epidermal Cl41 cells by induction of cyclooxygenase-2 (COX-2) expression. To provide direct evidence for NFAT3 in the environmental carcinogen-caused carcinogenic effect, (+/-)-benzo[a]pyrene-7,8-diol-9,10-epoxide (B[a]PDE), an ultimate environmental carcinogen metabolized from benzo[a]pyrene, was utilized. /Investigators/ found that exposure of Cl41 cells to B[a]PDE was able to induce cell transformation in Cl41 cells, while specific knock-down of NFAT3 resulted in the dramatic inhibition of this cell transformation. The tumorigenicity of B[a]PDE-caused transformed cells was confirmed in nude mice, whereas the tumor formation of B[a]PDE-treated NFAT3 small interference RNA (siRNA) knock-down cells was significantly reduced. Further studies showed that the role of NFAT3 in B[a]PDE-caused cell transformation was mediated by up-regulation of its downstream targeted gene TNF. This conclusion was based on the findings that inhibition of NFAT3 activation by either FK506 or NFAT3 siRNA dramatically down-regulated the TNF induction upon B[a]PDE exposure, and that knock-down of TNF by its specific siRNA also led to abrogation of B[a]PDE-induced cell transformation in Cl41 cells and their tumorigenicity in nude mice. Collectively, these results provide direct evidence for the important role of NFAT3 activation in B[a]PDE-induced cell transformation by up-regulation of TNF expression in mouse epidermal Cl41 cells, further suggesting that B[a]PDE may exert its tumor promotion effect on skin carcinogenesis, at least partially, by inducing TNF expression.[Ouyang W et al; Carcinogenesis 28 (10): 2218-2226 (2007). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/17522069?dopt=Abstract" target=new>PubMed Abstract Previous studies have shown that polycyclic aromatic hydrocarbons (PAHs) mobilize intracellular Ca2+ in human T cells by inositol trisphosphate-dependent mechanisms resulting from activation of phospholipase C-gamma by SRC-related protein tyrosine kinases, thereby mimicking antigen-receptor activation. Ca2+ appears to play an important second messenger role in growth factor control of cell proliferation in human mammary epithelial cells (HMEC) such as the epidermal growth factor

receptor pathway. The purpose of the present studies was to determine if polycyclic aromatic hydrocarbons are able to increase intracellular Ca2+ in primary cultures of human mammary epithelial cells and increase cell proliferation. Two carcinogenic and two non-carcinogenic polycyclic aromatic hydrocarbons were tested for their ability to increase intracellular Ca2+ in human mammary epithelial cells. The carcinogenic polycyclic aromatic hydrocarbons dimethylbenz(a)anthracene (DMBA) and benzo[a] pyrene (BaP) were able to cause Ca2+ elevation in human mammary epithelial cells at early time points (2 hr) and caused sustained alterations in Ca2+ homeostasis (18 hr). Dimethylbenz(a)anthracene showed maximal effects at early time points (2 hr), while benzo(a)pyrene showed maximal effects on sustained Ca2- (18 hr). 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a potent dioxin and tumor promoter, produced maximal Ca2+ elevation at 2 hr, with a return to near baseline levels by 6 hr. The non-carcinogenic polycyclic aromatic hydrocarbons benzo[e]pyrene and anthracene did not significantly alter intracellular Ca2+ at any time point. alpha-Naphthoflavone significantly reduced the Ca2+ response induced by benzo(a)pyrene treatment, but not by dimethylbenz(a)anthracene or 2,3,7,8-Tetrachlorodibenzo-p-dioxin, suggesting that p450 lA or lB metabolism of benzo(a)pyrene may be important in the sustained Ca2+ elevating response. In evaluating the effects of benzo(a)pyrene on human mammary epithelial cells proliferation, benzo(a)pyrene was found to increase the number of cells recovered after 4 days in culture in the absence or presence of various concentrations of epidermal growth factor. These studies provide initial evidence that Ca2+ signaling may be associated with mitogenesis in human mammary epithelial cells, which may play a role in tumor promotion and progression produced by polycyclic aromatic hydrocarbons.[Tannheimer SL et al; Carcinogenesis 18 (6): 1177-82 (1997)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/9214600?dopt=Abstract" target=new>PubMed Abstract The p53 tumor suppressor is a mutational target of environmental carcinogen anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE). /Investigators/ now demonstrate that p53 plays an important role in regulation of cellular responses to BPDE. Exposure of p53-null H1299 human lung cancer cells to BPDE resulted in S and G(2) phase cell cycle arrest, but not mitotic block, which correlated with induction of cyclin B1 protein expression, down-modulation of cell division cycle 25C (Cdc25C) and Cdc25B protein levels, and hyperphosphorylation of Cdc25C (S216), cyclin-dependent kinase 1 (Cdk1; Y15), checkpoint kinase 1 (Chk1; S317 and S345) and Chk2 (T68). The BPDE-induced S phase block, but not the G(2)/M phase arrest, was significantly attenuated by knockdown of Chk1 protein level. The BPDE-mediated accumulation of sub-diploid fraction (apoptotic cells) was significantly decreased in H1299 cells transiently transfected with both Chk1 and Chk2 specific siRNAs. The H460 human lung cancer cell line (wild-type p53) was relatively more sensitive to BPDE-mediated growth inhibition and enrichment of sub-diploid apoptotic fraction compared with H1299 cells. The BPDE exposure failed to activate either S or G(2) phase checkpoint in H460 cells. Instead, the BPDE-treated H460 cells exhibited a nearly 8-fold increase in sub-diploid apoptotic cells that was accompanied by phosphorylation of p53 at multiple sites. Knockdown of p53 protein level in H460 cells attenuated BPDE-induced apoptosis but enforced activation of S and G(2) phase checkpoints. In conclusion, the present study points towards an important role of p53 in regulation of cellular responses to BPDE in human lung cancer cells.[Xiao H et al; Cell cycle (Georgetown, Tex.) 6 (14): 1753-1761 (2007). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/17630511?dopt=Abstract" target=new>PubMed Abstract

Benzo[a]pyrene (BaP) is a ubiquitous environmental pollutant, which may contribute to the development of human cancer. The ultimate carcinogenic BaP metabolite produced by cytochrome P450 enzymes (CYP), such as CYP1A1 and CYP1B1, anti-BaP-7,8-diol-9,10-epoxide, binds covalently to DNA and causes mutations. The levels of various CYP isoforms can be significantly modulated under inflammatory conditions. As the chronic inflammation is known to contribute to carcinogenesis, we investigated interactions of a major proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), and BaP in regulation of the expression of CYP1A1/1B1 and induction of DNA damage in rat liver epithelial WB-F344 cells. TNF-alpha enhanced induction of CYP1B1, while it simultaneously suppressed the BaP-induced CYP1A1 expression. The observed deregulation of CYP1 induction was found to be associated with a significantly enhanced formation of DNA adducts. The elevated DNA damage corresponded with increased phosphorylation of p53 tumor suppressor at Ser-15 residue, enhanced accumulation of cells in the S-phase of cell cycle and potentiation of BaP-induced apoptosis. Inhibition of CYP1B1 by fluoranthene significantly decreased both the formation of DNA adducts and the induction of apoptosis in WB-F344 cells treated with BaP and TNF-alpha, thus suggesting that this isoform might be responsible for genotoxic effects of BaP in nonparenchymal liver cells. Our results seem to indicate that inflammatory conditions might enhance genotoxic effects of carcinogenic polycyclic aromatic hydrocarbons through upregulation of CYP1B1 expression.[Umannova L et al; Mutation research 640 (1-2): 162-169 (2008). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/18336843?dopt=Abstract" target=new>PubMed Abstract Benzo[a]pyrene (BaP), a potent carcinogen, has been shown to induce apoptosis via activation of caspase-3. However, the upstream of caspase-3 and other apoptosis signaling remain to be elusive. Herein, /investigators/ demonstrated that treatment of Hepa1c1c7 cells with BaP increased the transcriptional expression of aryl hydrocarbon nuclear transporter and cytochrome P450 1A1 in a time and dose-dependent manner but did not aromatic hydrocarbon receptor. Also, the catalytic activation of caspase-3 and caspase-9 was induced whereas that of caspase-3 and caspase-9 was not by the addition of BaP. BaP also induced the mitochondrial dysfunction, including transition of mitochondria membrane potential and cytosolic release of cytochrome c. Furthermore, a decrease in the expression of Bcl-2 to Bax ratio and phosphorylation of p53(Ser 15) were observed in BaP-treated cells. Taken together, these results demonstrated that BaP-induced apoptosis of Hepa1c1c7 cells via activation of intrinsic caspase pathway including caspase-3, caspase-9, with mitochondrial dysfunction and p53 activation.[Ko CB et al; Toxicology 199 (1): 35-46 (2004). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/15125997?dopt=Abstract" target=new>PubMed Abstract In this study, /the authors/ investigated effects of benzo[a]pyrene (BP) on growth and functional differentiation of mouse bone marrow (BM)-derived dendritic cells (DC). 1 uM BP dramatically inhibited growth of BM cultured in the presence of granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4). Although little alterations in surface expression of CD11c, major histocompatibility complex (MHC II), and CD86 molecules characteristic of mature DC were induced by BP, production of cytokines including IL-12, IL-10, and TNF-alpha, and allogeneic T cell stimulating ability were severely impaired. Some of the effects of BP were dependent on arylhydrocarbon receptor (AhR), because alpha-naphthoflavone,

an AhR antagonist, suppressed the effects of BP on IL-12 production and T cell stimulating ability, but not on DC proliferation. Expression of RelB, a transcription factor necessary for DC differentiation and function, and eIF3 p170, a subunit of eukaryotic translation initiation factor (eIF)3, was reduced upon BP treatment.[Hwang J et al; Toxicology letters 169 (1): 82-90 (2007). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/17275222?dopt=Abstract" target=new>PubMed Abstract The activation by the carcinogenic polycyclic aromatic hydrocarbon (PAH) benzo[a]pyrene (BP) of transcription factors NF-kappaB and AP-1 in hepatoma 27 and HepG2 cell cultures was studied. In contrast to the hepatoma HepG2 cells, cytochrome P450 isoforms and Ah-receptor are not expressed in the hepatoma 27 cells. The transcription factor NF-kappaB was activated only in the hepatoma 27 cells by BP treatment but not by its noncarcinogenic isomer benzo[e]pyrene (BeP). Conversely to NF-kappaB activation the transcription factor AP-1 was activated in the hepatoma HepG2 cells by cell treatment with BP but not in the hepatoma 27 cells. It is concluded that the NF-kappaB activation is caused by nonmetabolized BP molecule and not related to activation of the Ah-receptor. The transcription factor AP-1 seems to be activated as a result of the interaction of BP with the Ah-receptor. The realization of tumor promotion stage by carcinogenic PAHs treatment in dependence on the cytochrome P450 and Ah-receptor levels in the initiated cells is discussed.[Bolotina NA et al; Biochemistry (Biokhimiya) 72 (5): 552-557 (2007). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/17573710?dopt=Abstract" target=new>PubMed Abstract CYP1A1 and CYP1B1 metabolically activate many polycyclic aromatic hydrocarbons (PAHs), including benzo[a]pyrene, to reactive intermediates associated with toxicity, mutagenesis, and carcinogenesis. Paradoxically, however, Cyp1a1-/- knockout mice are more sensitive to oral benzo[a]pyrene exposure, compared with wild-type Cyp1a1+/+ mice ... To further investigate the mechanism for this enhanced sensitivity, Cyp1a1-/-, Cyp1a2-/-, and Cyp1b1-/- single-knockout, Cyp1a1/1b1-/- and Cyp1a2/1b1-/double-knockout, and Cyp1+/+ wild-type mice were analyzed. After administration of oral benzo[a]pyrene (125 mg/kg/day) for 18 days, Cyp1a1-/- mice showed marked wasting, immunosuppression, and bone marrow hypocellularity, whereas the other five genotypes did not. After 5 days of feeding, steady-state blood levels of benzo[a]pyrene were approximately 25 and approximately 75 times higher in Cyp1a1-/- and Cyp1a1/1b1-/- mice, respectively, than in wild-type mice. Benzo[a]pyrene-DNA adduct levels were highest in liver, spleen, and marrow of Cyp1a1-/- and Cyp1a1/1b1-/mice. Many lines of convergent data obtained with oral benzo[a]pyrene dosing suggest that: 1) inducible CYP1A1, probably in both intestine and liver, is most important in detoxication; 2) CYP1B1 in spleen and marrow is responsible for metabolic activation of benzo[a]pyrene, which results in immune damage in the absence of CYP1A1; 3) both thymus atrophy and hepatocyte hypertrophy are independent of CYP1B1 metabolism but rather may reflect long-term activation of the aryl hydrocarbon receptor; and 4) the magnitude of immune damage in Cyp1a1-/- and Cyp1a1/1b1-/- mice is independent of plasma benzo[a]pyrene and total-body burden and clearance. Thus, a balance between tissue-specific expression of the CYP1A1 and CYP1B1 enzymes governs sensitivity of benzo[a]pyrene toxicity and, possibly, carcinogenicity.[Uno S et al; Mol Pharmacol 69 (4): 1103-1114 (2006). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/16377763?dopt=Abstract" target=new>PubMed Abstract

AhR repressor (AhRR) is an AhR-related bHLH-PAS transcription factor. It is known to repress AhR transcription activity in a competitive manner. To examine AhRR functions in mice, we produced AhRR-deficient mice by gene knockout. AhRR(-/-) mice were born in normal Mendelian proportions, grew well, and were fertile. AhR(-/-) mice exhibited higher levels of Cyp1a1 (Cytochrome P450 1A1) mRNA induction in the skin, stomach and spleen than wild-type mice, while expression of Cyp1a1 mRNA was not significantly altered in the liver, lung, heart or other tissues, suggesting that "super-induction" of Cyp1a1 mRNA expression in AhRR(-/-) mice occurs in a tissue specific manner. AhRR(-/-) mice displayed a delayed response to skin carcinogenesis caused by benzo[a]pyrene. Since CYP1A1 is involved in the metabolic activation and detoxification of chemical carcinogens, these results suggest that overexpression of CYP1A1 shifts the balance of the metabolic activities in the skin of AhRR(-/-) mice in favor of the detoxification of carcinogens.[Hosoya T et al; Biochemical and biophysical research communications 365 (3): 562-567 (2008). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/18022386?dopt=Abstract" target=new>PubMed Abstract INTERACTIONS: Squamous cell carcinogens were tabulated in rats exposed to atmospheres of SO2 or benzo[a]pyrene alone, or to both in combination, 5 days per wk for their lifetime. No cancers were produced in 15 animals exposed to SO2 alone (10 ppm, 6 hr/day), and one cancer in 30 animals exposed to 10 mg/cu m of benzo(a)pyrene along (1 hr a day). Exposure to SO2 (10 ppm, 6 hr/day) and then to an SO2 (4 ppm) - benz[a]pyrene (10 mg/cu m) mixture for 1 hr a day produced 9 cancers in 46 rats.[European Commission, ESIS; IUCLID Dataset, Sulfur dioxide (CAS #7446-09-5) p.62 (2000 CD-ROM edition). Available from, as of November 9, 2009: http://esis.jrc.ec.europa.eu/] **PEER REVIEWED** Intratracheal instillations of combinations of lead oxide and benzo[a]pyrene in hamsters produced lung tumours not observed with either agent alone.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V87 7 (2006)] **PEER REVIEWED** The association of small quantities of ferric oxide with benzo[a]pyrene (BaP) appears to increase in vivo the toxic effect of benzo[a]pyrene. The effect of Fe203 may be mediated by the recruitment of alveolar macrophages. These cells would contribute to the production of toxic and carcinogenic benzo[a]pyrene metabolites and would stimulate development of tumors by producing cellular mediators of inflammation. In order to understand the mechanism of the synergic effect, we have instillated male Sprague Dawley rats 3 weeks of age with a single dose: Fe203 (3 mg) or benzo[a]pyrene (3 mg)/combination Fe203-benzo[a]pyrene (3 mg-3 mg) in 200 uL of physiological saline solution. Control group of identical size (treated with physiological saline solutions and untreated were used for this study. Animals were sacrificed 48 hours after instillation and a bronchoalveolar lavage (BAL) was performed. With each bronchoalveolar lavage we have obtained protein measurement, cells were stained with May-Grunwald-Giemsa method and slides were studied with polarized light. The malonaldehyde (MDA) was measured by High Performance Liquid Chromatography. The PMN elastase determination was performed by IMAC (immuno-activation) technology. An automated kinetic method for measuring cathepsins B and L was carried out using a fluorogenic substrate: Z-Phe-Arg-AMC, a specific inhibitor E64 and AMC as an internal standard.

After a quantitative Dot-Blot of the samples of bronchoalveolar lavage, an immunodetection of alpha(l)-antitrypsin (alpha(l)AT) was performed. The inhibitory capacity of alpha(l)antitrypsin was determined by an enzymatic reaction with porcine pancreatic elastase. We have observed an increased malonaldehyde level for rats intoxicated with Fe203 (123%), benzo[a]pyrene (31%) and Fe203 + benzo[a]pyrene (56%). The levels of PMN elastase and cathepsin B and L were increased: Fe203 (51-58%), benzo[a]pyrene (52-27%). This effect was not seen for rats intoxicated by Fe203 + benzo[a]pyrene. The free alpha(l)antitrypsin was decreased with the three toxics (Fe203: 44%--benzo[a]pyrene: 42%--Fe203: 41%). The inhibitory capacity of alpha(l)antitrypsin was lower in groups of rats instilled with toxics.[Gosset P et al; Cent Eur J Public Health (4): 56-7 (1996)] **PEER REVIEWED** ... To determine whether co-exposure (Benzo(a)Pyrene/iron oxides) induces a real genotoxic activity or is only due to inhibition of DNA repair, the unscheduled DNA synthesis (UDS) assay was implemented in vivo in the rat. The UDS assay was used to measure DNA repair in two cell types (lung cells and hepatocytes) of OFA Sprague-Dawley rats, 24 hr after endotracheal administration of a single dose of an iron oxide (hematite, Fe2O3) (0.75 mg), of Benzo(a)Pyrene (0.75 mg) or of Benzo(a)Pyrene (0.75 mg) coated on hematite particles (0.75 mg). No difference in UDS was observed in the two organs investigated in rats treated with iron oxide alone compared with control animals, while a significant increase in UDS was observed in lungs and liver of rats treated with Benzo(a)Pyrene alone compared with control animals. The main finding was a significant increase in UDS observed in both lung and liver cells of rats treated with Benzo(a)Pyrene coated on hematite when compared with those treated with Benzo(a)Pyrene alone ...[Garry S et al; Mutagenesis 18 (5): 449-455 (2003). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/12960414?dopt=Abstract" target=new>PubMed Abstract Experimental evidence suggests that inorganic lead and benzo[a]pyrene (BaP) suppress the development of primordial oocytes during fetal life. We examined the single and combined effects of prenatal exposure to benzo[a]pyrene and moderate doses of lead. The fertility and ovarian morphology of Fl female NMRI mice in four treatment groups (nine mice per group) were investigated: control; lead (F0 given 1 g PbC12/L in drinking water until mating); benzo[a]pyrene (10 mg/kg bw daily by oral intubation on days 7-16 of F0 pregnancy); and combined lead and benzo[a]pyrene. Fl groups exposed prenatally to benzo[a]pyrene either alone or in combination with inorganic lead showed markedly reduced fertility with few ovarian follicles compared to controls, whereas the group exposed to lead only had measures comparable to the controls. Mice exposed to both lead and benzo[a]pyrene had a significantly longer gestation period (days to litter) compared to mice exposed only to benzo[a]pyrene, lead, or controls. There is a nonsignificant indication that the compounds together further reduce number of offspring, number of litters, and litter size. These results suggest that lead and benzo[a]pyrene have synergistic effects on impairment of fertility. The possibility of synergism may be of human relevance as inorganic lead and benzo[a]pyrene are ubiquitous environmental pollutants.[Kristensen P et al; Environ Health Perspect 103 (6): 588-90 (1995)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/7556012?dopt=Abstract" target=new>PubMed Abstract ... Experimental evidence supports the antineoplastic effect of selenium with regard to benzo[a]pyrene-induced ... skin tumors in mice.[Doull, J., C.D.Klassen, and M.D. Amdur (eds.). Casarett and Doull's Toxicology. 3rd

ed., New York: Macmillan Co., Inc., 1986., p. 617] **PEER REVIEWED** Rabbits treated with benzo[a]pyrene developed cardiac arrhythmias when exposed by inhalation to 8100 ppm trichloroethylene or 15000 ppm halothane to a greater extent and at lower doses of epinephrine challenge than did controls. Benzo(a)pyrene increased the metabolism of trichloroethylene. The basis of the arrhythmogenic action of benzo[a]pyrene was unrelated to its ability to induce xenobiotic metabolism.[Carlson GP, White JF; Toxicol Lett (Amst) 15 (1): 43-8 (1983)] **PEER REVIEWED** The effect of Ginkgo biloba extracts and some of its individual constituents on the catalytic activity of human cytochrome P450 enzymes CYP1B1, CYP1A1, and CYP1A2 /was examined/. G. biloba extract of known abundance of terpene trilactones and flavonol glycosides inhibited 7-ethoxyresorufin O-dealkylation catalyzed by human recombinant CYP1B1, CYP1A1, and CYP1A2, and human liver microsomes, with apparent Ki values of 2 +/- 0.3, 5 +/- 0.5, 16 +/- 1.4, and 39 +/- 1.2 ug/mL (mean +/- SE), respectively. In each case, the mode of inhibition was of the mixed type. ... G. biloba extract also reduced benzo[a]pyrene hydroxylation, and the effect was greater with CYP1B1 than with CYP1A1 as the catalyst.[Chang KH et al; Toxicology and Applied Pharmacology 213 (1): 18-26 (2006). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/16226778?dopt=Abstract" target=new>PubMed Abstract ... The effects of NaAsO(2) in combination with benzo[a]pyrene (BAP) on CYP1A1 and CYP1B1 in T-47D human breast cancer cells /was investigated/ by using estrogen metabolism as a probe of their activities. Exposure to BAP caused elevated rates of the 2- and 4-hydroxylation pathways of estrogen metabolism, indicating induction of both CYP1A1, an estradiol 2-hydroxylase, and CYP1B1, an estradiol 4-hydroxylase. BAP-induced metabolism peaked 9 to 16 hr after exposure and returned to near-basal levels by 48 hr. Concentration-response studies showed maximal induction of the 2- and 4-hydroxylation pathways at 3 uM BAP; higher levels caused reduced rates of metabolism due to inhibition of CYP1A1 and CYP1B1. NaAsO(2) caused pronounced decreases in the induction of CYP1A1 and CYP1B1 by 3 uM BAP because cotreatment with 10 uM NaAsO(2) inhibited the rates of the 2- and 4-hydroxylation pathways by 86 and 92%, respectively. Western immunoblots showed diminished levels of BAP-induced CYP1A1 by coexposure to NaAsO(2). The levels of the CYP1A1 and CYP1B1 mRNAs induced by BAP were not significantly affected by coexposure to NaAsO(2); however, heme oxygenase 1 mRNA levels were markedly induced by coexposure to BAP and NaAsO(2). These results indicate a post-transcriptional inhibitory effect of arsenite on the expression of CYP1A1 and CYP1B1 in T-47D cells, possibly resulting from reduced heme availability.[Spink DC et al; Drug metabolism and disposition: the biological fate of chemicals 30 (3): 262269 (2002). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/11854143?dopt=Abstract" target=new>PubMed Abstract In mouse hepatic microsomes, dietary butylated hydroxyanisole (BHA) enhanced the total metabolism of benzo[a]pyrene (BaP) but decreased the microsomal metabolism of (BP)-7,8-diol, especially the formation of (BP)-trans-7,8-diol-anti-9,10-oxide. The altered metabolism of benzo(a)pyrene is believed to be due to the induction of new cytochrome p450 species by dietary BHA. Thus, BHA can affect BaP metabolism by exerting its inhibitory effect directly and by altering the composition of microsomal monooxygenase enzymes after a few days of exposure.[Sydor W Jr et al; Carcinogenesis 4 (2): 131-6 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6297821?dopt=Abstract"

target=new>PubMed Abstract Ip injection of channel catfish (Ictalurus punctatus) with 100 ug benzo[a]pyrene, Aroclor 1254, or naphthalene, singly and in combinations, affected the levels of the brain neurotransmitters norepinephrine, dopamine, and 5-hydroxytryptamine, but the effect showed no discernible pattern. The effects of combinations of the chemicals did not appear to be predictable from the effects of individual chemicals. In several instances, the change in the level of neurotransmitter in fish receiving a combination of chemicals was greater than in fish receiving either chemical alone.[Fingerman SW, Short EC; Bull Environ Contam Toxicol 30 (2): 147-51 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6132633?dopt=Abstract" target=new>PubMed Abstract The modifying effect of solvents on the carcinogenicity of BaP is well demonstrated by comparison between the effects of 3 weekly paintings with different concn of BaP either in n-dodecane/decalin (50:50 mixture) or in decalin on C3H/He mice. When n-dodecane/decalin was the solvent, 5 malignant tumors appeared among l24 mice painted with the lowest concn ... 0.00002%, and the tumor incidence increased at higher doses. With decalin, no skin tumors developed in any ... mice below 0.02% concn.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V3 105 (1973)] **PEER REVIEWED** In an inhalation study, a group of 21 rats exposed to mixture of 10 mg/cu m BaP and 3.5 ppm SO2 /sulfur dioxide/ for 1 hr/day for more than a yr, 2 developed squamous cell carcinomas of lung. In another group of 21 rats which received additional treatment with SO2 of 10 ppm for 6 hr/day, squamous cell carcinomas appeared in five rats. No tumors were found among 3 rats receiving SO2 only. No group was exposed to BaP alone.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V3 107 (1973)] **PEER REVIEWED** Piperine, a major component of black pepper and long peppers, has been reported previously to have an effect on the activation and deactivation of some exogenous substances. In the present study, piperine was found to promote DNA damage and cytotoxicity induced by benzo[a]pyrene (BaP) in cultured V-79 lung fibroblast cells. The V-79 cells were treated with a non-toxic dose of piperine (1-20 uM) plus 10 uM benzo[a]pyrene, or pretreated with piperine for 30 min or 2 hr prior to the administration of 10 uM benzo[a]pyrene. Benzo[a]pyrene cytotoxicity was potentiated significantly by piperine under each experimental condition. The relative plating efficiency (RPE) was 71% when V-79 cells were exposed to 10 uM benzo[a]pyrene alone. When the culture was exposed to benzo[a]pyrene plus piperine or pretreated with piperine for 30 min prior to the administration of benzo[a]pyrene, the RPE values were 63 and 44% (P < 0.001), respectively. Pretreatment with piperine for 2 hr had no significant effect (P > 0.05). Furthermore, the lowest activities (P > 0.05) of glutathione S-transferase (GST) and uridine diphosphate glucuronyl transferase (UDP-GTase) of piperine-treated V-79 cells occurred 30 min to 1 hr after the piperine pretreatment. Pretreatment of V-79 cells with piperine also caused an increase in the covalent binding of benzo[a]pyrene-diol-epoxide to DNA, 2.3 times greater than that of the V-79 cells without piperine treatment. These results suggest that the promotion by piperine of benzo[a]pyrene-induced cytotoxicity in V-79 lung

fibroblast cells is due to mechanisms that decrease the activities of GST and UDP-GTase and increase the formation of a benzo[a]pyrene-DNA adduct.[Chu CY et al; Food Chem Toxicol 32 (4): 373-7 (1994)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/8206433?dopt=Abstract" target=new>PubMed Abstract The commonly used spice and flavoring agent, rosemary, derived from the leaves of the plant Rosmarinus officinalis L., displays antioxidant properties in foods and in biological systems. Moreover, in animal models rosemary components were found to inhibit the initiation and tumor promotion phases of carcinogenesis. In this work, we studied the mechanisms by which rosemary components block initiation of carcinogenesis by the procarcinogen benzo[a]pyrene (BaP) in human bronchial epithelial cells (BEAS-2B). Whole rosemary extract (6 ug/mL) or an equivalent concentration of its most potent antioxidant constituents, carnosol or carnosic acid, inhibited DNA adduct formation by 80% after 6 hr co-incubation with 1.5 uM benzo[a]pyrene. Under similar conditions, cytochrome p450 (CYP) lA1 mRNA expression was 50% lower in the presence of rosemary components, and CYPlAI activity was inhibited 70-90%. The observed reduction of DNA adduct formation by rosemary components may mostly result from the inhibition of the activation of benzo[a] pyrene to its ultimate metabolites. Carnosol also affected expression of the phase II enzyme glutathione-S-transferase which is known to detoxify the proximate carcinogenic metabolite of benzo[a]pyrene. Treatment of BEAS-2B cells with carnosol (1 ug/mL) for 24 hr resulted in a 3- to 4-fold induction of GST pi mRNA. Moreover, expression of a second important phase II enzyme, NAD(P)H: quinone reductase, was induced by carnosol in parallel with GST pi. Therefore, rosemary components have the potential to decrease activation and increase detoxification of an important human carcinogen, identifying them as promising candidates for chemopreventive programs.[Offord EA et al; Carcinogenesis 16 (9): 2057-62 (1995)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/7554054?dopt=Abstract" target=new>PubMed Abstract In vitro studies on the effect of alcoholic extracts of turmeric (TE), turmeric oil (TO) and turmeric oleores in (TOR), on the incidence of micronuclei (Mn) in lymphocytes from normal healthy subjects showed that the test compounds did not cause any increase in the number of micronuclei as compared with those found in untreated controls. Further it was observed that all three compounds offered protection against benzo[a]pyrene induced increase in micronuclei in circulating lymphocytes.[Hastak K et al; Cancer Lett 116 (2): (1997)] **PEER REVIEWED** A water extract of raw garlic (RGE) and two organosulfur compounds, diallyl sulfide and S-allylcysteine (SAC), were evaluated for their relative effectiveness in reducing benzo[a]pyrene (BaP)-DNA adduct formation in stimulated human peripheral blood lymphocytes in vitro. In replicate experiments, raw garlic significantly inhibited benzo[a]pyrene-DNA adduct formation at concentrations of 0.001, 0.01, and 0.1 mg/mL. S-allylcysteine also significantly decreased benzo[a]pyrene-DNA adduct formation at concentrations of 0.01 and 0.1 mg/mL. For diallyl sulfide, no significant reduction in benzo[a]pyrene-DNA adduct formation was found. Benzo[a]pyrene-DNA adduct formation was not associated with cell viability or proliferation of peripheral blood lymphocytes after the various treatments. No clear scavenging activity was detected for the garlic constituents. Aryl hydrocarbon hydroxylase activity was not decreased, nor was formation of sulfate and glucuronide conjugates of

3-hydroxy-benzo[a]pyrene increased in the presence of raw garlic and S-allylcysteine, indicating that increased glutathione S-transferase activity or a more efficient repair of benzo[a]pyrene-DNA adducts may explain the observed effects. In addition, reactive oxygen species-induced 8-oxodeoxyguanosine in DNA was reduced in the presence of S-allylcysteine. It is concluded that raw garlic and S-allylcysteine may be useful in the prevention of benzo[a]pyrene-associated tumorigenesis and that further evaluation of their preventive potential in humans at risk appears feasible.[Hageman GJ et al; Nutr Cancer 27 (2): 177-85 (1997)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/9121947?dopt=Abstract" target=new>PubMed Abstract The chemopreventive activity of S-(N,N-diethyldithiocarbamoyl)-N-acetyl-L-cysteine against benzo[a]pyrene (BaP) /was investigated/ in the Salmonella typhimurium bacterial mutation assay, in the chromosome aberration assay using Chinese hamster lung fibroblast (CHL), and in the mouse micronucleus assay in bone marrow cells. In the bacterial mutation assay, S-(N,N-diethyldithiocarbamoyl)-N-acetyl-L-cysteine produced a concentration dependent decrease in the number of mutant colonies induced by benzo[a]pyrene. The chromosome damaging responses of benzo[a]pyrene in Chinese hamster lung cells were abolished by the treatment of S-(N,N-diethyldithiocarbamoyl)-N-acetyl-L-cysteine, approximately to the level of the control. In the in vivo mouse bone marrow micronucleus test, pretreatment of S-(N,N-diethyldithiocarbamoyl)-N-acetyl-L-cysteine 1 hr prior to benzo[a]pyrene reduced the frequency of micronucleated polychromatic erythrocytes. The inhibitory effects were statistically significant and dose-dependent...[Lee BH et al; Mutat Res 377 (2): 167-75 (1997)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/9247612?dopt=Abstract" target=new>PubMed Abstract The purpose of this study was to investigate the influence of benzylisothiocyanate (BIT) and 13-cis-retinoic acid (RA) upon the genotoxic potential of benzo[a]pyrene (BaP) to induce micronucleus formation in the bone marrow of mice. Eighty-two male mice were divided into 10 groups. One group served as a negative control (olive oil intubation). Four groups received an oral intubation of various concentrations of benzylisothiocyanate (15 to 120 mg/kg) and ip injections of benzo[a]pyrene (185 mg/kg). Another four groups were treated identically, but received 13-cis-retinoic acid (20 to 150 mg/kg) in place of benzylisothiocyanate. Finally, one group received only ip injection of benzo[a]pyrene (185 mg/kg). The results showed that both benzylisothiocyanate and 13-cis-retinoic acid significantly reduced the frequency of micronucleus formation in the bone marrow of the benzo[a]pyrene treated animals. Benzylisothiocyanate was found to be effective at all the tested concentrations. 13-cis-retinoic acid was effective only at three of the four tested concentrations (40, 75 and 150 mg/kg). These findings indicate that both benzylisothiocyanate and 13-cis-retinoic acid may reduce the genotoxic effects of benzo[a]pyrene in the mice under the test conditions utilized.[Aldosari A et al; Mutat Res 352 (l-2): 1-7 (1996)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/8676899?dopt=Abstract" target=new>PubMed Abstract ... Four different treatment schemes of combinations of benzo[a]pyrene and eugenol were examined in Hep G2 cells: pre-treatment with eugenol; simultaneous treatment with eugenol and benzo[a]pyrene; a combination of these (pretreatment/simultaneous treatment); and post-treatment with

eugenol. An increase in the genotoxicity of benzo[a]pyrene was found in Hep G2 cells. No effect of eugenol on the genotoxicity of benzo[a]pyrene was found with the pre- and post-treatments. It is concluded that the effect of eugenol on genotoxicity induced by established mutagens is not univocal; in vivo treatment of rats with eugenol resulted in a reduction of the mutagenicity of benzo[a]pyrene in the S. typhimurium mutagenicity assay, while in the unscheduled DNA synthesis assay no effect of eugenol was found. In vitro treatment of cultured cells with eugenol resulted in an increase in genotoxicity of benzo[a]pyrene. These findings indicate that there is only limited support for the antigenotoxic potential of eugenol in vivo.[Rompelberg CJ et al; Food Chem Toxicol 34 (1): 33-42 (1996)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/8603795?dopt=Abstract" target=new>PubMed Abstract ... When dibenzo[a,l]pyrene, dibenzoa,e]pyrene and benzo[a]pyrene were applied together to /the skin of male Parkes mice/, a total binding 31% lower than expected was detected, while with a mixture of dibenzo[a,e]pyrene and benzo[a]pyrene the binding to DNA in skin was 65% higher than expected from the binding levels of the carcinogenes when applied singly. Other binary combinations of these three polycyclic aromatic hydrocarbons gave adduct levels similar to the sum of the binding levels of the individual components when applied singly.[Hughes NC, Phillips DH; Carcinogenesis (EYNSHAM); 11 (9): 1611-20 (1990)] **PEER REVIEWED** Benzo[a]pyrene (BaP) is able to inhibit the mutagenicity of l-nitropyrene (l-NP) through the reduction of nitroreductase activity and formation of adducts with DNA...[Cherng SH et al; H Mutat Res 367 (4): 177-85 (1996)] **PEER REVIEWED** Male brook trout (Salvelinus fontinalis) were given a single intraperitoneal injection of either BaP (10 mg/kg), tributyltin (TBT) (10 mg/kg), or both in combination. After 48 hr, blood, bile, and liver samples were collected and analyzed for a suite of biomarkers associated with P450 activity, BaP metabolism and bioactivation, and TBT metabolism. The results showed that TBT significantly (p < 0.05; two-way analysis of variance) inhibited (a) the induction of hepatic P450 1A-mediated ethoxyresorufin O-deethylase (EROD) and P450-mediated 3-cyano-7-ethoxycoumarin-O-deethylase (CN-ECOD) activities by BaP, (b) the formation of biliary BaP metabolites, and (c) the formation of (+)-anti-BPDE-plasma albumin adducts... . TBT alone did not inhibit EROD activity but induced CN-ECOD activity (p < 0.05). ... Te combined BaP + TBT dose resulted in higher levels of dibutyltin metabolites in the bile (p < 0.05). /This/ study supports the hypothesis that a single, high dose of TBT can antagonize the metabolism and bioactivation of BaP at least by inhibiting the induction of P4501A. On the other hand, BaP unexpectedly potentiated the metabolism of TBT, suggesting that hepatic isoforms other than P4501A may be responsible for TBT metabolism.[Padros J et al; Environ Toxicol Chem 19 (4): 1019-27 (2000)] **PEER REVIEWED** In this study, /the authors/ evaluated whether oral kava could prevent 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) plus benzo[a]pyrene (BaP)-induced lung tumorigenesis in A/J mice. /Investigators/ also studied the effect of kava to liver. At a dose of 10 mg/g diet, 30-week kava treatment (8 weeks concurrent with NNK and BaP treatment followed by 22 weeks post-carcinogen treatment) effectively reduced lung tumor multiplicity by 56%. Kava also reduced lung tumor multiplicity by 47% when administered concurrently with NNK and B[a]P for 8 weeks. Perhaps most importantly, kava reduced lung tumor multiplicity by 49% when administered

after the final NNK and B[a]P treatment. These results show for the first time the chemopreventive potential of kava against lung tumorigenesis. Mechanistically, kava inhibited proliferation and enhanced apoptosis in lung tumors, as shown by a reduction in proliferating cell nuclear antigen (PCNA), an increase in caspase-3, and cleavage of poly(ADP-ribose) polymerase (PARP). Kava treatment also inhibited the activation of nuclear factor kappaBNF-kappaB, a potential upstream mechanism of kava chemoprevention. Although not rigorously evaluated in this study, preliminary data were not suggestive of hepatotoxicity...[Johnson TE et al; Cancer Prevention Research (Philadelphia, Pa.) 1 (6): 430-438 (2008). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/19138990?dopt=Abstract" target=new>PubMed Abstract Exposure of mouse hepatoma Hepa-1 cells to low concentrations of arsenite increases BaP-DNA adduct levels by as much as 18-fold. This effect requires the activation of BaP by cytochrome P450 1A1 (CYP1A1), although arsenite does not alter BaP-inducible CYP1A1 enzymatic activity, suggesting that arsenite acts downstream of metabolic BaP activation. Glutathione homeostasis was important in modulating the potency of arsenite. In cells depleted of reduced glutathione, arsenite increased BaP-DNA adduct formation by an even greater degree than in cells co-treated with BaP and arsenite in control medium. Although arsenic comutagenicity has been attributed to inhibition of DNA repair, arsenite treatment did not alter adduct removal kinetics in BaP-treated cells, suggesting that mechanisms upstream of DNA repair are responsible for increased adduct levels. Concentrations of arsenite and BaP that had no measurable mutagenic effect alone, increased mutation frequency at the Hprt locus by eight-fold when given in combination, demonstrating a comutagenic response between BaP and arsenite. These results provide strong support for the positive interaction between arsenic and PAH-induced cancer observed in epidemiology studies, and help to identify additional mechanistic steps likely to be involved in arsenic comutagenesis.[Maier A et al; Mutation research 517 (1-2): 101-111 (2002). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/12034312?dopt=Abstract" target=new>PubMed Abstract The aim of the present study is to /examine/ the chemopreventive nature of hesperidin during benzo[a]pyrene (BaP) induced lung cancer in Swiss albino mice. Administration of BaP (50 mg/kg body weight) to mice resulted in increased lipid peroxides (LPO), lung specific tumor marker carcinoembryonic antigen (CEA) and serum marker enzymes aryl hydrocarbon hydroxylase (AHH), gamma glutamyl transpeptidase (GGT), 5'nucleotidase (5'ND) and lactate dehydrogenase (LDH) with concomitant decrease in the levels of tissue antioxidants like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), vitamin E and vitamin C. Hesperidin supplementation (25 mg/kg body weight) significantly attenuated these alterations thereby showing potent anticancer effect in lung cancer...[Kamaraj S et al; Investigational new drugs 27 (3): 214-222 (2009). Available from, as of November 23,2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/18704264?dopt=Abstract" target=new>PubMed Abstract /Investigators/ tested the chemopreventive efficacy of indole-3-carbinol (I3C), a constituent of Brassica vegetables, and its major condensation product, 3,3'-diindolylmethane (DIM), against lung tumorigenesis induced by a mixture of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (BaP) in A/J mice. The mixture of NNK plus BaP (2 umol

each) was administered by gavage as eight weekly doses, whereas I3C (112 micromol/g diet) and DIM (2 and 30 micromol/g diet in experiments 1 and 2, respectively) were given in the diet for 23 weeks beginning at 50% of carcinogen treatment. I3C reduced NNK plus BaP-induced tumor multiplicity by 78% in experiment 1 and 86% in experiment 2; the respective reductions in tumor multiplicity by DIM were 5% and 66%. Using a quantitative proteomics method, isobaric tags for relative and absolute quantitation (iTRAQ) coupled with mass spectrometry, /investigators/ identified and quantified at least 250 proteins in lung tissues. Of these proteins, nine showed differences in relative abundance in lung tissues of carcinogen-treated versus untreated mice: fatty acid synthase, transketolase, pulmonary surfactant-associated protein C (SP-C), L-plastin, annexin A1, and haptoglobin increased, whereas transferrin, alpha-1-antitrypsin, and apolipoprotein A-1 decreased. Supplementation of the diet of carcinogen-treated mice with I3C reduced the level of SP-C, L-plastin, annexin A1, and haptoglobin to that of untreated controls. These results were verified using immunoblotting. /The authors/ show here that tumor-associated signature proteins are increased during NNK plus BaP-induced lung carcinogenesis, and I3C inhibits this effect, suggesting that the lung tumor chemopreventive activity of I3C might be related to modulation of carcinogen-induced alterations in protein levels.[Kassie F et al; Cancer research 67 (13): 6502-6511 (2007). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/17616712?dopt=Abstract" target=new>PubMed Abstract Combined subcarcinogenic doses of benzo[a]pyrene (BaP) and UVA induced H-ras, but not p53, gene mutations 8 weeks before tumor emergence in SKH-1 mice. Neither UVA (40 kJ/sq m) nor BaP (8 nmol) induced any tumors after mice were topically treated 3 times/week for 25 weeks. However, combined BaP-UVA treatment synergistically increased tumor incidence and multiplicity. All tumors induced by BaP-UVA were malignant. The epidermis was collected from mice treated for 2, 6 and 10 weeks. DNA from UVB- (0.3 kJ/sq m) or BaP-UVA-(8 nmol and 40 kJ/sq m-induced tumors was isolated and screened for H-ras and p53 mutations. Four types of point mutation, GGC-- > GAC, GCC, GTC and CGC, occurred in UVB-induced tumors at H-ras codon 13; and one type of point mutation, GGA-- > GAA, at codon 12. Treatment with either BaP alone or BaP-UVA for 10 weeks caused GGA-- > GAA mutation at codon 12 or GGC-- > GAC mutation at codon 13 in nontumor skin, respectively, as well as in tumors induced by BaP-UVA. All of the 10-week samples treated with either BaP or BaP-UVA showed detectable mutations at codons 12 and 13, but the genetic load was significantly higher in BaP-UVA-treated mice than in those exposed only to BaP. UVA alone induced mutations at codon 12 in only one-third of samples. G-- > A mutations induced by BaP or BaP-UVA at position 38 of codon 13 have not been reported previously. C-- > T transitions were detected in p53 hot spots of exon 8 in 2 of 19 BaP-UVA-induced tumors but were not found in nontumor skin.[Wang Y et al; International Journal of Cancer (Journal international du cancer) 116 (2): 193-199 (2005). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/15800929?dopt=Abstract" target=new>PubMed Abstract ... A previous study in rat lung epithelial cells showed that cell transformation frequency increased by more than 100-fold when arsenic was given in combination with B[a]P than cells either exposed to arsenic or BaP alone. This demonstrated a synergism between them. Here, ... alterations to the proteome varied and were more pronounced in the transformed cells that were exposed to a combination of arsenic and BaP than to BaP and much less to arsenic alone when compared to

passage-matched control cells. In general, three proteins belonging to intermediate filaments were found to be significantly down-regulated and six proteins belonging to antioxidative stress-, chaperone-, and glycolytic proteins were up-regulated in these transformed cells. These transformed cells were also associated with an increase of proliferation and de-differentiation. Taken together, /these/ findings suggest that although arsenic or BaP alone is sufficient to induce cell transformation and alter the proteome to a similar extent, the effects of coexposure are much more pronounced. This further substantiates the notion that these carcinogens act in concert during cocarcinogenesis.[Lau AT et al; Proteomics 6 (5): 1619-1630 (2006). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/16456883?dopt=Abstract" target=new>PubMed Abstract Three-month-old Swiss-derived SHR mice were subcutaneously injected with 2 mg of benzo[a]pyrene (BP) dissolved in 0.1 mL of olive oil. After the injections of the carcinogen two groups of mice were given melatonin with night drinking water at the doses of 2 mg/L or 20 mg/L and one group of mice was not treated with melatonin and served as a PB-control. At the 28th week after the carcinogen administration the experiment was stopped and animals were sacrificed. The results show that melatonin treatment inhibits BP-induced carcinogenesis, decreases the incidence of subcutaneous sarcomas, increases their latency and survival of mice. The malone dialdehyde (MDA) level in the serum of BP-induced tumor-bearing mice was increased by 2.6 times (p < 0.01) and in the tumors was increased by 11.1% (p < 0.01) as compared to intact control mice. Treatment with melatonin significantly decreased the MDA level both in the serum and tumor tissue. The activity of catalase in the serum of BP-induced tumor-bearing mice was increased by 12.1% as compared to the intact control mice (p < 0.01) and was unchanged in the tumor tissue. Treatment with melatonin at the dose of 2 mg/l significantly decreased activity of catalase in the serum (by 31.7%, p < 0.01) and in the tumor tissue (by 2.6 times, p < 0.01) as compared to the animals treated with BP alone. Thus, ... an inhibitory effect of melatonin on malignancies of mesenchymal origin /was shown/. Lower dose of melatonin appeared to be more effective in the inhibition of lipid peroxidation and tumorigenesis induced by chemical carcinogen than a higher one.[Vesnushkin GM et al; Journal of experimental &amp; clinical cancer research: CR 25 (4): 507-513 (2006). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/17310841?dopt=Abstract" target=new>PubMed Abstract The efficacy of mangiferin on the antioxidant status of benzo[a]pyrene-induced lung carcinogenesis in Swiss albino mice was assessed. The animals were divided into five groups. The animals in groups I and V were normal control and mangiferin control, respectively. Groups II, III and IV were administered with benzo[a]pyrene (50 mg/kg body weight, orally) for 4 weeks (twice a week) to induced lung carcinogenesis. Starting 1 week prior to benzo[a]pyrene administration, group III animals were treated with mangiferin (100 mg/kg body weight) in the diet for 18 weeks; 12 weeks after benzo[a]pyrene administration, group III animals were treated with mangiferin that continued until the end of the experiment period (18 weeks). At the end of the experiment period, the reactive oxygen species, glutathione and the activities of antioxidant enzymes were assessed in both lung and liver tissues. The levels of glutathione, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, vitamin E and vitamin C were decreased in group II animals. However, in the mangiferin + benzo[a]pyrene-treated groups III and IV, the levels of GSH and the activities of antioxidant enzymes in

both lung and liver were improved when compared with benzo[a]pyrene-induced group II animals. In addition, the finding that mangiferin decreased reactive oxygen species levels and enhanced antioxidant status suggests that this polyphenol might also be of value in the prevention of benzo[a]pyrene-induced lung carcinogenesis.[Rajendran P et al; Basic &amp; Clinical Pharmacology &amp; Toxicology 103 (2): 137-142 (2008). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/18816296?dopt=Abstract" target=new>PubMed Abstract PHARMACOLOGY: THERAPEUTIC USES: /EXPERIMENTAL THERAPY/ A 1% soln of benzo[a]pyrene in benzene was applied daily to protected and unprotected surfaces of skin of 26 patients suffering from pemphigus vulgaris, mycosis fungoides, prokeratosis, xeroderma pigmentosum, basal cell cancer, squamous cell cancer, lupus erythematosis, psoriasis, syphilis in various stages, or ringworm. The period of application did not exceed 4 mo, and diam of treated area was 2 cm. A progressive series of alterations developed in normal skin (chronically): erythema, pigmentation, desquamation, formation of verrucae, /clinically not true verrucae/ and infiltration. The manifestations regressed completely within 2 to 3 mo of cessation of treatment. Clinically, perceptible erythema occurred in only 2 patients with basal cell cancer. Pigmentation, which occurred in all patients, consisted of an increase in melanin in basal cell layer of epidermis and was more evident in exposed skin (eg, hand, face). It developed more readily in skin of senile individuals than in younger patients. Rarely, small masses of pigment granules were found in the more superficial layers. Desquamation was proportional in extent to erythema of the 1st stage. The formation of verrucae was the most constant manifestation caused by treatment. The skin of patient with xeroderma pigmentosum did not react differently ... from that of other patients.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V32 216 (1983)] **PEER REVIEWED** INTERACTIONS: Squamous cell carcinogens were tabulated in rats exposed to atmospheres of SO2 or benzo[a]pyrene alone, or to both in combination, 5 days per wk for their lifetime. No cancers were produced in 15 animals exposed to SO2 alone (10 ppm, 6 hr/day), and one cancer in 30 animals exposed to 10 mg/cu m of benzo(a)pyrene along (1 hr a day). Exposure to SO2 (10 ppm, 6 hr/day) and then to an SO2 (4 ppm) - benz[a]pyrene (10 mg/cu m) mixture for 1 hr a day produced 9 cancers in 46 rats.[European Commission, ESIS; IUCLID Dataset, Sulfur dioxide (CAS #7446-09-5) p.62 (2000 CD-ROM edition). Available from, as of November 9, 2009: http://esis.jrc.ec.europa.eu/] **PEER REVIEWED** Intratracheal instillations of combinations of lead oxide and benzo[a]pyrene in hamsters produced lung tumours not observed with either agent alone.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V87 7 (2006)] **PEER REVIEWED**

The association of small quantities of ferric oxide with benzo[a]pyrene (BaP) appears to increase in vivo the toxic effect of benzo[a]pyrene. The effect of Fe203 may be mediated by the recruitment of alveolar macrophages. These cells would contribute to the production of toxic and carcinogenic benzo[a]pyrene metabolites and would stimulate development of tumors by producing cellular mediators of inflammation. In order to understand the mechanism of the synergic effect, we have instillated male Sprague Dawley rats 3 weeks of age with a single dose: Fe203 (3 mg) or benzo[a]pyrene (3 mg)/combination Fe203-benzo[a]pyrene (3 mg-3 mg) in 200 uL of physiological saline solution. Control group of identical size (treated with physiological saline solutions and untreated were used for this study. Animals were sacrificed 48 hours after instillation and a bronchoalveolar lavage (BAL) was performed. With each bronchoalveolar lavage we have obtained protein measurement, cells were stained with May-Grunwald-Giemsa method and slides were studied with polarized light. The malonaldehyde (MDA) was measured by High Performance Liquid Chromatography. The PMN elastase determination was performed by IMAC (immuno-activation) technology. An automated kinetic method for measuring cathepsins B and L was carried out using a fluorogenic substrate: Z-Phe-Arg-AMC, a specific inhibitor E64 and AMC as an internal standard. After a quantitative Dot-Blot of the samples of bronchoalveolar lavage, an immunodetection of alpha(l)-antitrypsin (alpha(l)AT) was performed. The inhibitory capacity of alpha(l)antitrypsin was determined by an enzymatic reaction with porcine pancreatic elastase. We have observed an increased malonaldehyde level for rats intoxicated with Fe203 (123%), benzo[a]pyrene (31%) and Fe203 + benzo[a]pyrene (56%). The levels of PMN elastase and cathepsin B and L were increased: Fe203 (51-58%), benzo[a]pyrene (52-27%). This effect was not seen for rats intoxicated by Fe203 + benzo[a]pyrene. The free alpha(l)antitrypsin was decreased with the three toxics (Fe203: 44%--benzo[a]pyrene: 42%--Fe203: 41%). The inhibitory capacity of alpha(l)antitrypsin was lower in groups of rats instilled with toxics.[Gosset P et al; Cent Eur J Public Health (4): 56-7 (1996)] **PEER REVIEWED** ... To determine whether co-exposure (Benzo(a)Pyrene/iron oxides) induces a real genotoxic activity or is only due to inhibition of DNA repair, the unscheduled DNA synthesis (UDS) assay was implemented in vivo in the rat. The UDS assay was used to measure DNA repair in two cell types (lung cells and hepatocytes) of OFA Sprague-Dawley rats, 24 hr after endotracheal administration of a single dose of an iron oxide (hematite, Fe2O3) (0.75 mg), of Benzo(a)Pyrene (0.75 mg) or of Benzo(a)Pyrene (0.75 mg) coated on hematite particles (0.75 mg). No difference in UDS was observed in the two organs investigated in rats treated with iron oxide alone compared with control animals, while a significant increase in UDS was observed in lungs and liver of rats treated with Benzo(a)Pyrene alone compared with control animals. The main finding was a significant increase in UDS observed in both lung and liver cells of rats treated with Benzo(a)Pyrene coated on hematite when compared with those treated with Benzo(a)Pyrene alone ...[Garry S et al; Mutagenesis 18 (5): 449-455 (2003). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/12960414?dopt=Abstract" target=new>PubMed Abstract Experimental evidence suggests that inorganic lead and benzo[a]pyrene (BaP) suppress the development of primordial oocytes during fetal life. We examined the single and combined effects of prenatal exposure to benzo[a]pyrene and moderate doses of lead. The fertility and ovarian morphology of Fl female NMRI mice in four treatment groups (nine mice per group) were investigated: control; lead (F0 given 1 g PbC12/L in drinking water until mating); benzo[a]pyrene (10 mg/kg bw daily by oral intubation

on days 7-16 of F0 pregnancy); and combined lead and benzo[a]pyrene. Fl groups exposed prenatally to benzo[a]pyrene either alone or in combination with inorganic lead showed markedly reduced fertility with few ovarian follicles compared to controls, whereas the group exposed to lead only had measures comparable to the controls. Mice exposed to both lead and benzo[a]pyrene had a significantly longer gestation period (days to litter) compared to mice exposed only to benzo[a]pyrene, lead, or controls. There is a nonsignificant indication that the compounds together further reduce number of offspring, number of litters, and litter size. These results suggest that lead and benzo[a]pyrene have synergistic effects on impairment of fertility. The possibility of synergism may be of human relevance as inorganic lead and benzo[a]pyrene are ubiquitous environmental pollutants.[Kristensen P et al; Environ Health Perspect 103 (6): 588-90 (1995)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/7556012?dopt=Abstract" target=new>PubMed Abstract ... Experimental evidence supports the antineoplastic effect of selenium with regard to benzo[a]pyrene-induced ... skin tumors in mice.[Doull, J., C.D.Klassen, and M.D. Amdur (eds.). Casarett and Doull's Toxicology. 3rd ed., New York: Macmillan Co., Inc., 1986., p. 617] **PEER REVIEWED** Rabbits treated with benzo[a]pyrene developed cardiac arrhythmias when exposed by inhalation to 8100 ppm trichloroethylene or 15000 ppm halothane to a greater extent and at lower doses of epinephrine challenge than did controls. Benzo(a)pyrene increased the metabolism of trichloroethylene. The basis of the arrhythmogenic action of benzo[a]pyrene was unrelated to its ability to induce xenobiotic metabolism.[Carlson GP, White JF; Toxicol Lett (Amst) 15 (1): 43-8 (1983)] **PEER REVIEWED** The effect of Ginkgo biloba extracts and some of its individual constituents on the catalytic activity of human cytochrome P450 enzymes CYP1B1, CYP1A1, and CYP1A2 /was examined/. G. biloba extract of known abundance of terpene trilactones and flavonol glycosides inhibited 7-ethoxyresorufin O-dealkylation catalyzed by human recombinant CYP1B1, CYP1A1, and CYP1A2, and human liver microsomes, with apparent Ki values of 2 +/- 0.3, 5 +/- 0.5, 16 +/- 1.4, and 39 +/- 1.2 ug/mL (mean +/- SE), respectively. In each case, the mode of inhibition was of the mixed type. ... G. biloba extract also reduced benzo[a]pyrene hydroxylation, and the effect was greater with CYP1B1 than with CYP1A1 as the catalyst.[Chang KH et al; Toxicology and Applied Pharmacology 213 (1): 18-26 (2006). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/16226778?dopt=Abstract" target=new>PubMed Abstract ... The effects of NaAsO(2) in combination with benzo[a]pyrene (BAP) on CYP1A1 and CYP1B1 in T-47D human breast cancer cells /was investigated/ by using estrogen metabolism as a probe of their activities. Exposure to BAP caused elevated rates of the 2- and 4-hydroxylation pathways of estrogen metabolism, indicating induction of both CYP1A1, an estradiol 2-hydroxylase, and CYP1B1, an estradiol 4-hydroxylase. BAP-induced metabolism peaked 9 to 16 hr after exposure and returned to near-basal levels by 48 hr. Concentration-response studies showed maximal induction of the 2- and 4-hydroxylation pathways at 3 uM BAP; higher levels caused reduced rates of metabolism due to inhibition of CYP1A1 and CYP1B1. NaAsO(2) caused pronounced decreases in the induction of CYP1A1 and CYP1B1 by 3 uM BAP because cotreatment with 10 uM NaAsO(2) inhibited the rates of the 2- and 4-hydroxylation pathways by 86 and 92%, respectively. Western immunoblots showed diminished levels of BAP-induced CYP1A1 by coexposure to NaAsO(2). The levels of the CYP1A1 and CYP1B1 mRNAs induced by BAP were

not significantly affected by coexposure to NaAsO(2); however, heme oxygenase 1 mRNA levels were markedly induced by coexposure to BAP and NaAsO(2). These results indicate a post-transcriptional inhibitory effect of arsenite on the expression of CYP1A1 and CYP1B1 in T-47D cells, possibly resulting from reduced heme availability.[Spink DC et al; Drug metabolism and disposition: the biological fate of chemicals 30 (3): 262269 (2002). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/11854143?dopt=Abstract" target=new>PubMed Abstract In mouse hepatic microsomes, dietary butylated hydroxyanisole (BHA) enhanced the total metabolism of benzo[a]pyrene (BaP) but decreased the microsomal metabolism of (BP)-7,8-diol, especially the formation of (BP)-trans-7,8-diol-anti-9,10-oxide. The altered metabolism of benzo(a)pyrene is believed to be due to the induction of new cytochrome p450 species by dietary BHA. Thus, BHA can affect BaP metabolism by exerting its inhibitory effect directly and by altering the composition of microsomal monooxygenase enzymes after a few days of exposure.[Sydor W Jr et al; Carcinogenesis 4 (2): 131-6 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6297821?dopt=Abstract" target=new>PubMed Abstract Ip injection of channel catfish (Ictalurus punctatus) with 100 ug benzo[a]pyrene, Aroclor 1254, or naphthalene, singly and in combinations, affected the levels of the brain neurotransmitters norepinephrine, dopamine, and 5-hydroxytryptamine, but the effect showed no discernible pattern. The effects of combinations of the chemicals did not appear to be predictable from the effects of individual chemicals. In several instances, the change in the level of neurotransmitter in fish receiving a combination of chemicals was greater than in fish receiving either chemical alone.[Fingerman SW, Short EC; Bull Environ Contam Toxicol 30 (2): 147-51 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6132633?dopt=Abstract" target=new>PubMed Abstract The modifying effect of solvents on the carcinogenicity of BaP is well demonstrated by comparison between the effects of 3 weekly paintings with different concn of BaP either in n-dodecane/decalin (50:50 mixture) or in decalin on C3H/He mice. When n-dodecane/decalin was the solvent, 5 malignant tumors appeared among l24 mice painted with the lowest concn ... 0.00002%, and the tumor incidence increased at higher doses. With decalin, no skin tumors developed in any ... mice below 0.02% concn.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V3 105 (1973)] **PEER REVIEWED** In an inhalation study, a group of 21 rats exposed to mixture of 10 mg/cu m BaP and 3.5 ppm SO2 /sulfur dioxide/ for 1 hr/day for more than a yr, 2 developed squamous cell carcinomas of lung. In another group of 21 rats which received additional treatment with SO2 of 10 ppm for 6 hr/day, squamous cell carcinomas appeared in five rats. No tumors were found among 3 rats receiving SO2 only. No group was exposed to BaP alone.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V3 107 (1973)] **PEER REVIEWED** Piperine, a major component of black pepper and long peppers, has been reported previously to have an effect on the activation and deactivation

of some exogenous substances. In the present study, piperine was found to promote DNA damage and cytotoxicity induced by benzo[a]pyrene (BaP) in cultured V-79 lung fibroblast cells. The V-79 cells were treated with a non-toxic dose of piperine (1-20 uM) plus 10 uM benzo[a]pyrene, or pretreated with piperine for 30 min or 2 hr prior to the administration of 10 uM benzo[a]pyrene. Benzo[a]pyrene cytotoxicity was potentiated significantly by piperine under each experimental condition. The relative plating efficiency (RPE) was 71% when V-79 cells were exposed to 10 uM benzo[a]pyrene alone. When the culture was exposed to benzo[a]pyrene plus piperine or pretreated with piperine for 30 min prior to the administration of benzo[a]pyrene, the RPE values were 63 and 44% (P < 0.001), respectively. Pretreatment with piperine for 2 hr had no significant effect (P > 0.05). Furthermore, the lowest activities (P > 0.05) of glutathione S-transferase (GST) and uridine diphosphate glucuronyl transferase (UDP-GTase) of piperine-treated V-79 cells occurred 30 min to 1 hr after the piperine pretreatment. Pretreatment of V-79 cells with piperine also caused an increase in the covalent binding of benzo[a]pyrene-diol-epoxide to DNA, 2.3 times greater than that of the V-79 cells without piperine treatment. These results suggest that the promotion by piperine of benzo[a]pyrene-induced cytotoxicity in V-79 lung fibroblast cells is due to mechanisms that decrease the activities of GST and UDP-GTase and increase the formation of a benzo[a]pyrene-DNA adduct.[Chu CY et al; Food Chem Toxicol 32 (4): 373-7 (1994)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/8206433?dopt=Abstract" target=new>PubMed Abstract The commonly used spice and flavoring agent, rosemary, derived from the leaves of the plant Rosmarinus officinalis L., displays antioxidant properties in foods and in biological systems. Moreover, in animal models rosemary components were found to inhibit the initiation and tumor promotion phases of carcinogenesis. In this work, we studied the mechanisms by which rosemary components block initiation of carcinogenesis by the procarcinogen benzo[a]pyrene (BaP) in human bronchial epithelial cells (BEAS-2B). Whole rosemary extract (6 ug/mL) or an equivalent concentration of its most potent antioxidant constituents, carnosol or carnosic acid, inhibited DNA adduct formation by 80% after 6 hr co-incubation with 1.5 uM benzo[a]pyrene. Under similar conditions, cytochrome p450 (CYP) lA1 mRNA expression was 50% lower in the presence of rosemary components, and CYPlAI activity was inhibited 70-90%. The observed reduction of DNA adduct formation by rosemary components may mostly result from the inhibition of the activation of benzo[a] pyrene to its ultimate metabolites. Carnosol also affected expression of the phase II enzyme glutathione-S-transferase which is known to detoxify the proximate carcinogenic metabolite of benzo[a]pyrene. Treatment of BEAS-2B cells with carnosol (1 ug/mL) for 24 hr resulted in a 3- to 4-fold induction of GST pi mRNA. Moreover, expression of a second important phase II enzyme, NAD(P)H: quinone reductase, was induced by carnosol in parallel with GST pi. Therefore, rosemary components have the potential to decrease activation and increase detoxification of an important human carcinogen, identifying them as promising candidates for chemopreventive programs.[Offord EA et al; Carcinogenesis 16 (9): 2057-62 (1995)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/7554054?dopt=Abstract" target=new>PubMed Abstract In vitro studies on the effect of alcoholic extracts of turmeric (TE), turmeric oil (TO) and turmeric oleores in (TOR), on the incidence of micronuclei (Mn) in lymphocytes from normal healthy subjects showed that the test compounds did not cause any increase in the number of micronuclei

as compared with those found in untreated controls. Further it was observed that all three compounds offered protection against benzo[a]pyrene induced increase in micronuclei in circulating lymphocytes.[Hastak K et al; Cancer Lett 116 (2): (1997)] **PEER REVIEWED** A water extract of raw garlic (RGE) and two organosulfur compounds, diallyl sulfide and S-allylcysteine (SAC), were evaluated for their relative effectiveness in reducing benzo[a]pyrene (BaP)-DNA adduct formation in stimulated human peripheral blood lymphocytes in vitro. In replicate experiments, raw garlic significantly inhibited benzo[a]pyrene-DNA adduct formation at concentrations of 0.001, 0.01, and 0.1 mg/mL. S-allylcysteine also significantly decreased benzo[a]pyrene-DNA adduct formation at concentrations of 0.01 and 0.1 mg/mL. For diallyl sulfide, no significant reduction in benzo[a]pyrene-DNA adduct formation was found. Benzo[a]pyrene-DNA adduct formation was not associated with cell viability or proliferation of peripheral blood lymphocytes after the various treatments. No clear scavenging activity was detected for the garlic constituents. Aryl hydrocarbon hydroxylase activity was not decreased, nor was formation of sulfate and glucuronide conjugates of 3-hydroxy-benzo[a]pyrene increased in the presence of raw garlic and S-allylcysteine, indicating that increased glutathione S-transferase activity or a more efficient repair of benzo[a]pyrene-DNA adducts may explain the observed effects. In addition, reactive oxygen species-induced 8-oxodeoxyguanosine in DNA was reduced in the presence of S-allylcysteine. It is concluded that raw garlic and S-allylcysteine may be useful in the prevention of benzo[a]pyrene-associated tumorigenesis and that further evaluation of their preventive potential in humans at risk appears feasible.[Hageman GJ et al; Nutr Cancer 27 (2): 177-85 (1997)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/9121947?dopt=Abstract" target=new>PubMed Abstract The chemopreventive activity of S-(N,N-diethyldithiocarbamoyl)-N-acetyl-L-cysteine against benzo[a]pyrene (BaP) /was investigated/ in the Salmonella typhimurium bacterial mutation assay, in the chromosome aberration assay using Chinese hamster lung fibroblast (CHL), and in the mouse micronucleus assay in bone marrow cells. In the bacterial mutation assay, S-(N,N-diethyldithiocarbamoyl)-N-acetyl-L-cysteine produced a concentration dependent decrease in the number of mutant colonies induced by benzo[a]pyrene. The chromosome damaging responses of benzo[a]pyrene in Chinese hamster lung cells were abolished by the treatment of S-(N,N-diethyldithiocarbamoyl)-N-acetyl-L-cysteine, approximately to the level of the control. In the in vivo mouse bone marrow micronucleus test, pretreatment of S-(N,N-diethyldithiocarbamoyl)-N-acetyl-L-cysteine 1 hr prior to benzo[a]pyrene reduced the frequency of micronucleated polychromatic erythrocytes. The inhibitory effects were statistically significant and dose-dependent...[Lee BH et al; Mutat Res 377 (2): 167-75 (1997)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/9247612?dopt=Abstract" target=new>PubMed Abstract The purpose of this study was to investigate the influence of benzylisothiocyanate (BIT) and 13-cis-retinoic acid (RA) upon the genotoxic potential of benzo[a]pyrene (BaP) to induce micronucleus formation in the bone marrow of mice. Eighty-two male mice were divided into 10 groups. One group served as a negative control (olive oil intubation). Four groups received an oral intubation of various concentrations of benzylisothiocyanate (15 to 120 mg/kg) and ip injections

of benzo[a]pyrene (185 mg/kg). Another four groups were treated identically, but received 13-cis-retinoic acid (20 to 150 mg/kg) in place of benzylisothiocyanate. Finally, one group received only ip injection of benzo[a]pyrene (185 mg/kg). The results showed that both benzylisothiocyanate and 13-cis-retinoic acid significantly reduced the frequency of micronucleus formation in the bone marrow of the benzo[a]pyrene treated animals. Benzylisothiocyanate was found to be effective at all the tested concentrations. 13-cis-retinoic acid was effective only at three of the four tested concentrations (40, 75 and 150 mg/kg). These findings indicate that both benzylisothiocyanate and 13-cis-retinoic acid may reduce the genotoxic effects of benzo[a]pyrene in the mice under the test conditions utilized.[Aldosari A et al; Mutat Res 352 (l-2): 1-7 (1996)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/8676899?dopt=Abstract" target=new>PubMed Abstract ... Four different treatment schemes of combinations of benzo[a]pyrene and eugenol were examined in Hep G2 cells: pre-treatment with eugenol; simultaneous treatment with eugenol and benzo[a]pyrene; a combination of these (pretreatment/simultaneous treatment); and post-treatment with eugenol. An increase in the genotoxicity of benzo[a]pyrene was found in Hep G2 cells. No effect of eugenol on the genotoxicity of benzo[a]pyrene was found with the pre- and post-treatments. It is concluded that the effect of eugenol on genotoxicity induced by established mutagens is not univocal; in vivo treatment of rats with eugenol resulted in a reduction of the mutagenicity of benzo[a]pyrene in the S. typhimurium mutagenicity assay, while in the unscheduled DNA synthesis assay no effect of eugenol was found. In vitro treatment of cultured cells with eugenol resulted in an increase in genotoxicity of benzo[a]pyrene. These findings indicate that there is only limited support for the antigenotoxic potential of eugenol in vivo.[Rompelberg CJ et al; Food Chem Toxicol 34 (1): 33-42 (1996)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/8603795?dopt=Abstract" target=new>PubMed Abstract ... When dibenzo[a,l]pyrene, dibenzoa,e]pyrene and benzo[a]pyrene were applied together to /the skin of male Parkes mice/, a total binding 31% lower than expected was detected, while with a mixture of dibenzo[a,e]pyrene and benzo[a]pyrene the binding to DNA in skin was 65% higher than expected from the binding levels of the carcinogenes when applied singly. Other binary combinations of these three polycyclic aromatic hydrocarbons gave adduct levels similar to the sum of the binding levels of the individual components when applied singly.[Hughes NC, Phillips DH; Carcinogenesis (EYNSHAM); 11 (9): 1611-20 (1990)] **PEER REVIEWED** Benzo[a]pyrene (BaP) is able to inhibit the mutagenicity of l-nitropyrene (l-NP) through the reduction of nitroreductase activity and formation of adducts with DNA...[Cherng SH et al; H Mutat Res 367 (4): 177-85 (1996)] **PEER REVIEWED** Male brook trout (Salvelinus fontinalis) were given a single intraperitoneal injection of either BaP (10 mg/kg), tributyltin (TBT) (10 mg/kg), or both in combination. After 48 hr, blood, bile, and liver samples were collected and analyzed for a suite of biomarkers associated with P450 activity, BaP metabolism and bioactivation, and TBT metabolism. The results showed that TBT significantly (p < 0.05; two-way analysis of variance) inhibited (a) the induction of hepatic P450 1A-mediated ethoxyresorufin O-deethylase (EROD) and P450-mediated 3-cyano-7-ethoxycoumarin-O-deethylase (CN-ECOD) activities by BaP, (b) the

formation of biliary BaP metabolites, and (c) the formation of (+)-anti-BPDE-plasma albumin adducts... . TBT alone did not inhibit EROD activity but induced CN-ECOD activity (p < 0.05). ... Te combined BaP + TBT dose resulted in higher levels of dibutyltin metabolites in the bile (p < 0.05). /This/ study supports the hypothesis that a single, high dose of TBT can antagonize the metabolism and bioactivation of BaP at least by inhibiting the induction of P4501A. On the other hand, BaP unexpectedly potentiated the metabolism of TBT, suggesting that hepatic isoforms other than P4501A may be responsible for TBT metabolism.[Padros J et al; Environ Toxicol Chem 19 (4): 1019-27 (2000)] **PEER REVIEWED** In this study, /the authors/ evaluated whether oral kava could prevent 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) plus benzo[a]pyrene (BaP)-induced lung tumorigenesis in A/J mice. /Investigators/ also studied the effect of kava to liver. At a dose of 10 mg/g diet, 30-week kava treatment (8 weeks concurrent with NNK and BaP treatment followed by 22 weeks post-carcinogen treatment) effectively reduced lung tumor multiplicity by 56%. Kava also reduced lung tumor multiplicity by 47% when administered concurrently with NNK and B[a]P for 8 weeks. Perhaps most importantly, kava reduced lung tumor multiplicity by 49% when administered after the final NNK and B[a]P treatment. These results show for the first time the chemopreventive potential of kava against lung tumorigenesis. Mechanistically, kava inhibited proliferation and enhanced apoptosis in lung tumors, as shown by a reduction in proliferating cell nuclear antigen (PCNA), an increase in caspase-3, and cleavage of poly(ADP-ribose) polymerase (PARP). Kava treatment also inhibited the activation of nuclear factor kappaBNF-kappaB, a potential upstream mechanism of kava chemoprevention. Although not rigorously evaluated in this study, preliminary data were not suggestive of hepatotoxicity...[Johnson TE et al; Cancer Prevention Research (Philadelphia, Pa.) 1 (6): 430-438 (2008). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/19138990?dopt=Abstract" target=new>PubMed Abstract Exposure of mouse hepatoma Hepa-1 cells to low concentrations of arsenite increases BaP-DNA adduct levels by as much as 18-fold. This effect requires the activation of BaP by cytochrome P450 1A1 (CYP1A1), although arsenite does not alter BaP-inducible CYP1A1 enzymatic activity, suggesting that arsenite acts downstream of metabolic BaP activation. Glutathione homeostasis was important in modulating the potency of arsenite. In cells depleted of reduced glutathione, arsenite increased BaP-DNA adduct formation by an even greater degree than in cells co-treated with BaP and arsenite in control medium. Although arsenic comutagenicity has been attributed to inhibition of DNA repair, arsenite treatment did not alter adduct removal kinetics in BaP-treated cells, suggesting that mechanisms upstream of DNA repair are responsible for increased adduct levels. Concentrations of arsenite and BaP that had no measurable mutagenic effect alone, increased mutation frequency at the Hprt locus by eight-fold when given in combination, demonstrating a comutagenic response between BaP and arsenite. These results provide strong support for the positive interaction between arsenic and PAH-induced cancer observed in epidemiology studies, and help to identify additional mechanistic steps likely to be involved in arsenic comutagenesis.[Maier A et al; Mutation research 517 (1-2): 101-111 (2002). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/12034312?dopt=Abstract" target=new>PubMed Abstract The aim of the present study is to /examine/ the chemopreventive nature of hesperidin during benzo[a]pyrene (BaP) induced lung cancer in Swiss albino

mice. Administration of BaP (50 mg/kg body weight) to mice resulted in increased lipid peroxides (LPO), lung specific tumor marker carcinoembryonic antigen (CEA) and serum marker enzymes aryl hydrocarbon hydroxylase (AHH), gamma glutamyl transpeptidase (GGT), 5'nucleotidase (5'ND) and lactate dehydrogenase (LDH) with concomitant decrease in the levels of tissue antioxidants like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), vitamin E and vitamin C. Hesperidin supplementation (25 mg/kg body weight) significantly attenuated these alterations thereby showing potent anticancer effect in lung cancer...[Kamaraj S et al; Investigational new drugs 27 (3): 214-222 (2009). Available from, as of November 23,2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/18704264?dopt=Abstract" target=new>PubMed Abstract /Investigators/ tested the chemopreventive efficacy of indole-3-carbinol (I3C), a constituent of Brassica vegetables, and its major condensation product, 3,3'-diindolylmethane (DIM), against lung tumorigenesis induced by a mixture of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (BaP) in A/J mice. The mixture of NNK plus BaP (2 umol each) was administered by gavage as eight weekly doses, whereas I3C (112 micromol/g diet) and DIM (2 and 30 micromol/g diet in experiments 1 and 2, respectively) were given in the diet for 23 weeks beginning at 50% of carcinogen treatment. I3C reduced NNK plus BaP-induced tumor multiplicity by 78% in experiment 1 and 86% in experiment 2; the respective reductions in tumor multiplicity by DIM were 5% and 66%. Using a quantitative proteomics method, isobaric tags for relative and absolute quantitation (iTRAQ) coupled with mass spectrometry, /investigators/ identified and quantified at least 250 proteins in lung tissues. Of these proteins, nine showed differences in relative abundance in lung tissues of carcinogen-treated versus untreated mice: fatty acid synthase, transketolase, pulmonary surfactant-associated protein C (SP-C), L-plastin, annexin A1, and haptoglobin increased, whereas transferrin, alpha-1-antitrypsin, and apolipoprotein A-1 decreased. Supplementation of the diet of carcinogen-treated mice with I3C reduced the level of SP-C, L-plastin, annexin A1, and haptoglobin to that of untreated controls. These results were verified using immunoblotting. /The authors/ show here that tumor-associated signature proteins are increased during NNK plus BaP-induced lung carcinogenesis, and I3C inhibits this effect, suggesting that the lung tumor chemopreventive activity of I3C might be related to modulation of carcinogen-induced alterations in protein levels.[Kassie F et al; Cancer research 67 (13): 6502-6511 (2007). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/17616712?dopt=Abstract" target=new>PubMed Abstract Combined subcarcinogenic doses of benzo[a]pyrene (BaP) and UVA induced H-ras, but not p53, gene mutations 8 weeks before tumor emergence in SKH-1 mice. Neither UVA (40 kJ/sq m) nor BaP (8 nmol) induced any tumors after mice were topically treated 3 times/week for 25 weeks. However, combined BaP-UVA treatment synergistically increased tumor incidence and multiplicity. All tumors induced by BaP-UVA were malignant. The epidermis was collected from mice treated for 2, 6 and 10 weeks. DNA from UVB- (0.3 kJ/sq m) or BaP-UVA-(8 nmol and 40 kJ/sq m-induced tumors was isolated and screened for H-ras and p53 mutations. Four types of point mutation, GGC-- > GAC, GCC, GTC and CGC, occurred in UVB-induced tumors at H-ras codon 13; and one type of point mutation, GGA-- > GAA, at codon 12. Treatment with either BaP alone or BaP-UVA for 10 weeks caused GGA-- > GAA mutation at codon 12 or GGC-- > GAC mutation at codon 13 in nontumor skin, respectively, as well as in tumors induced by BaP-UVA. All

of the 10-week samples treated with either BaP or BaP-UVA showed detectable mutations at codons 12 and 13, but the genetic load was significantly higher in BaP-UVA-treated mice than in those exposed only to BaP. UVA alone induced mutations at codon 12 in only one-third of samples. G-- > A mutations induced by BaP or BaP-UVA at position 38 of codon 13 have not been reported previously. C-- > T transitions were detected in p53 hot spots of exon 8 in 2 of 19 BaP-UVA-induced tumors but were not found in nontumor skin.[Wang Y et al; International Journal of Cancer (Journal international du cancer) 116 (2): 193-199 (2005). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/15800929?dopt=Abstract" target=new>PubMed Abstract ... A previous study in rat lung epithelial cells showed that cell transformation frequency increased by more than 100-fold when arsenic was given in combination with B[a]P than cells either exposed to arsenic or BaP alone. This demonstrated a synergism between them. Here, ... alterations to the proteome varied and were more pronounced in the transformed cells that were exposed to a combination of arsenic and BaP than to BaP and much less to arsenic alone when compared to passage-matched control cells. In general, three proteins belonging to intermediate filaments were found to be significantly down-regulated and six proteins belonging to antioxidative stress-, chaperone-, and glycolytic proteins were up-regulated in these transformed cells. These transformed cells were also associated with an increase of proliferation and de-differentiation. Taken together, /these/ findings suggest that although arsenic or BaP alone is sufficient to induce cell transformation and alter the proteome to a similar extent, the effects of coexposure are much more pronounced. This further substantiates the notion that these carcinogens act in concert during cocarcinogenesis.[Lau AT et al; Proteomics 6 (5): 1619-1630 (2006). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/16456883?dopt=Abstract" target=new>PubMed Abstract Three-month-old Swiss-derived SHR mice were subcutaneously injected with 2 mg of benzo[a]pyrene (BP) dissolved in 0.1 mL of olive oil. After the injections of the carcinogen two groups of mice were given melatonin with night drinking water at the doses of 2 mg/L or 20 mg/L and one group of mice was not treated with melatonin and served as a PB-control. At the 28th week after the carcinogen administration the experiment was stopped and animals were sacrificed. The results show that melatonin treatment inhibits BP-induced carcinogenesis, decreases the incidence of subcutaneous sarcomas, increases their latency and survival of mice. The malone dialdehyde (MDA) level in the serum of BP-induced tumor-bearing mice was increased by 2.6 times (p < 0.01) and in the tumors was increased by 11.1% (p < 0.01) as compared to intact control mice. Treatment with melatonin significantly decreased the MDA level both in the serum and tumor tissue. The activity of catalase in the serum of BP-induced tumor-bearing mice was increased by 12.1% as compared to the intact control mice (p < 0.01) and was unchanged in the tumor tissue. Treatment with melatonin at the dose of 2 mg/l significantly decreased activity of catalase in the serum (by 31.7%, p < 0.01) and in the tumor tissue (by 2.6 times, p < 0.01) as compared to the animals treated with BP alone. Thus, ... an inhibitory effect of melatonin on malignancies of mesenchymal origin /was shown/. Lower dose of melatonin appeared to be more effective in the inhibition of lipid peroxidation and tumorigenesis induced by chemical carcinogen than a higher one.[Vesnushkin GM et al; Journal of experimental &amp; clinical cancer research: CR 25 (4): 507-513 (2006). Available from, as of November 23, 2009:] **PEER REVIEWED** <a

href="http://www.ncbi.nlm.nih.gov/pubmed/17310841?dopt=Abstract" target=new>PubMed Abstract The efficacy of mangiferin on the antioxidant status of benzo[a]pyrene-induced lung carcinogenesis in Swiss albino mice was assessed. The animals were divided into five groups. The animals in groups I and V were normal control and mangiferin control, respectively. Groups II, III and IV were administered with benzo[a]pyrene (50 mg/kg body weight, orally) for 4 weeks (twice a week) to induced lung carcinogenesis. Starting 1 week prior to benzo[a]pyrene administration, group III animals were treated with mangiferin (100 mg/kg body weight) in the diet for 18 weeks; 12 weeks after benzo[a]pyrene administration, group III animals were treated with mangiferin that continued until the end of the experiment period (18 weeks). At the end of the experiment period, the reactive oxygen species, glutathione and the activities of antioxidant enzymes were assessed in both lung and liver tissues. The levels of glutathione, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, vitamin E and vitamin C were decreased in group II animals. However, in the mangiferin + benzo[a]pyrene-treated groups III and IV, the levels of GSH and the activities of antioxidant enzymes in both lung and liver were improved when compared with benzo[a]pyrene-induced group II animals. In addition, the finding that mangiferin decreased reactive oxygen species levels and enhanced antioxidant status suggests that this polyphenol might also be of value in the prevention of benzo[a]pyrene-induced lung carcinogenesis.[Rajendran P et al; Basic &amp; Clinical Pharmacology &amp; Toxicology 103 (2): 137-142 (2008). Available from, as of November 23, 2009:] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/18816296?dopt=Abstract" target=new>PubMed Abstract ENVIRONMENTAL FATE & EXPOSURE: ENVIRONMENTAL FATE/EXPOSURE SUMMARY: There is no commercial production or known use for benzo(a)pyrene; it is released to the environment as a product of incomplete combustion. Benzo(a)pyrene is found in fossil fuels, crude oils, shale oils, and coal tars, and is emitted with gases and fly ash from active volcanoes. If released to air, an extrapolated vapor pressure of 5.49X10-9 mm Hg at 25 deg C indicates benzo(a)pyrene will exist solely in the particulate phase in the atmosphere. Particulate-phase benzo(a)pyrene will be removed from the atmosphere by wet or dry deposition. Benzo(a)pyrene contains chromophores that absorb at wavelengths > 290 nm and therefore is expected to be susceptible to direct photolysis by sunlight; after 17 hours irradiation with light > 290 nm, 26.5% of BaP adsorbed onto silica gel was degraded. If released to soil, benzo(a)pyrene is expected to have very low to no mobility based upon measured soil Koc values of 930 to 6,300. Volatilization from moist soil surfaces is not expected to be an important fate process based upon a Henry's Law constant of 4.57X10-7 atm-cu m/mole. The persistence of benzo(a)pyrene in soil is expected to vary depending upon the nature of compounds accompanying it and the nature and previous history of the soil; biodegradation half-lives of 309 and 229 days were observed in Kidman and McLaurin sandy loam soils, respectively. If released into water, benzo(a)pyrene is expected to adsorb to suspended solids and sediment based upon the measured Koc values. Biodegradation of benzo(a)pyrene is expected to occur in aquatic systems; the removal of 64% of benzo(a)pyrene over 36 days in an activated sludge pilot reactor was attributed to biodegradation. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's

Henry's Law constant. Measured BCF values ranging from 8.7 to 1X10+5 suggest bioconcentration in aquatic organisms can be low to very high. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions. Occupational exposure to benzo(a)pyrene may occur through inhalation of air particulate matter via heating of organic material, and dermal contact with combustion products. Monitoring data indicate that the general population may be exposed to benzo(a)pyrene via inhalation of ambient air, ingestion of food and drinking water, smoking of tobacco, and cooking processes that produce smoke. (SRC) **PEER REVIEWED** PROBABLE ROUTES OF HUMAN EXPOSURE: ... Finished waters from various treatment sites are transported to consumers through a variety of pipelines. PAH's /polynuclear aromatic hydrocarbons/ leach from the tar or asphalt linings of these pipes ... resulting in increased concn of these cmpd in water reaching the consumers. ... Cement-lined pipes produce lower PAH concn, possibly because PAH's are adsorbed from water.[National Research Council. Drinking Water &amp; Health, Volume 4. Washington, DC: National Academy Press, 1981., p. 256] **PEER REVIEWED** IN GAS WORKS RETORT HOUSES MEAN CONCN RANGING FROM 1.4-4.8 MG/1000 CU M &amp; MAXIMUM CONCN OF 2300 MG/1000 CU M HAVE BEEN MEASURED ... 0.4 MG/1000 CU M /FOUND/ IN AIR POLLUTED BY COAL TAR PITCH FUMES, UP TO 2700 MG/1000 CU M IN INDUST EFFLUENTS &amp; 1000 MG/1000 CU M IN DOMESTIC COAL COMBUSTION STACK EFFLUENTS.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V3: 97 (1973)] **PEER REVIEWED** Influence of occupational ... factors upon benzo(a)pyrene exposure: Coke oven workers: Top side workers: 180 ug/day, side and bench exposure. 70 ug/day; Coal tar pitch worker: 750 ug/day; Airplane pilots: Transatlantic flights: 0.93 ug/day, domestic cross country: 1.38 ug/day; Employee in restraunt: 0.8 ug/day; Person living near expressway 24 hr/day (adverse meterology). 0.02 ug/day; Commuter on an expressway 2 hr/day (adverse meterology): 0.04 ug/day.[USEPA; Health Assessment Document for Polycyclic Organic Matter p.5-2 (1979) EPA-600/9-79-008] **PEER REVIEWED** Occupational situations involving heating organic materials may potentially result in exposure to this compound through inhalation of particulates or dermal contact with combustion products(1). Monitoring data indicate that the general population may be exposed to benzo(a)pyrene via smoking of tobacco, inhalation of polluted air, ingestion of food and drinking water contaminated by combustion effluents(2), and by cooking processes that produce smoke(SRC).[(1) Wallingford KM, Quehee SS; Polynuclear Aromatic Hydrocarbons: Mechanism, Methods, Metabolism. Cooke M, Dennis AJ, eds, Battelle Press (1985) (2) IARC; Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Polynuclear Aromatic Hydrocarbons Part I Chem and Environ Data 32: 211-24 (1983)] **PEER REVIEWED** Prior to renovations, coke oven workers wearing personal sampling pumps for a 6-8 hour shift were exposed to benzo(a)pyrene air concns ranging from, ug/cu m (workplace): 1.5 to 37 (battery top); 1.1 to 3.9 (coal conveyer); 1.7 to 12 (charging car); and 0.9 to 22 (oven doors); after renovation, exposure concns ranged from, ug/cu m (workplace): 0.2 to 6.8

(battery top); 0.1 to 1.7 (coal conveyer); and 0.2 to 0.3 (diverse)(1). Benzo(a)pyrene air concns for pot-room workers, detected using personal sampling pumps for 6-8 hours in a Soderberg aluminum plant were as follows, ug/cu m (workplace): 2.3 to 36 (pot-anode); 1.7 to 2.1 (cathode); and 2.8 to 4.4 (crane)(1). Benzo(a)pyrene concns in air of non-smoking road pavers and construction workers, detected using personal sampling pumps for 6-8 hours, was < 0.05 ug/cu m(1). In surveys using both area and personal samplers at 8 aluminum reduction plants, and at 21 coke production facilities in the U.S. and Europe, occupational exposure to benzo(a)pyrene ranged from 0.01-975 ug/cu m and 0.01-161 ug/cu m, respectively(2); Occupational exposure at 14 roofing sites, four roofing shingle manufacturing plants and eight petroleum refineries in the U.S. ranged from < 0.03-27, < 0.02-3.4, and < 0.01-9.3 ug/cu m, respectively(2). Benzo(a)pyrene was detected at the following worksites, ug/cu m: coal liquefaction, 0.01 to 19; coal gas works, 1.4 to 4.8 ug/cu m; hot forging, 1.6 to 2.9; tire manufacturing, 0.002 to 0.032; steel mill, 0.04 to 4.2; and carbon impregnation process, 0.80 to 84(2). In a rubber footwear plant in Moscow, time-weighted average benzo(a)pyrene concns in the breathing zone of workers was, ug/cu m: 0.022 for handling, weighing and mixing of raw materials; 0.026 for milling and extruding; 0.04 for assembly and building; 0.26 for curing or vulcanizing; 0.14 for inspection and finishing, and 0.020 for footwear casting(3). Benzo(a)pyrene air concns in the impregnation and handling of treated wood was < 0.03 ug/cu m, except in manual metal-arc welding and in the boring of railroad ties, where it was 0.24 to 0.89 ug/cu m(4). In a Norwegian aluminum plant, the median level of benzo(a)pyrene in personal air samples was 4.1 ug/cu m(5). Fifteen truck drivers from Geneva, Switzerland were exposed to mean benzo(a)pyrene concns of 3.45 and 0.77 ng/cu m for local and long-distance drivers, respectively, who were nonsmokers and 2.50 and 1.47 for local and long-distance drivers, respectively who were smokers; sampling pumps were placed beside the driver in the truck cabin(6).[(1) Levin JO et al; Sci Total Environ 163: 169-77 (1995) (2) Wallingford KM, Quehee SS; Polynuclear Aromatic Hydrocarbons: Mechanism, Methods, Metabolism. Cooke M, Dennis AJ, eds, Battelle Press (1985) (3) Solionova LG et al; Scand J Work Environ Health 18: 120-3 (1992) (4) Heikkila PR et al; Scand J Work Environ Health 13: 431-7 (1987) (5) Haugen A et al; Med Lav 83: 506-10 (1992) (6) Guillemin MP et al; Int Arch Occup Environ Health 63: 439-47 (1992)] **PEER REVIEWED** Emissions generated during the pouring, cooling, and shakeout of castings made with the evaporative pattern casting process contained benzo(a)pyrene at concns of 61 and 11 ug/kg for aluminum and iron castings, respectively(1). Stationary air samples collected near the ovens of two silicon carbide process plants contained benzo(a)pyrene concns ranging from 19 to 309 ng/cu m in one plant and 23 to 93 ng/cu m in the second plant(2). Benzo(a)pyrene was detected in air samples (taken at breathing height using personal sampling pumps) collected in the furnace area of two silicon carbide process plants at concns (ng/cu m) ranging from (Plant A and B): 17 to 103 and 39 to 79 for the foreman; 4 to 35 and 31 to 247 for the crane operator; 56 to 98 and 42 to 52 for oven workers whose tasks were in close proximity to the oven; and 9 to 43 and 385 to 632 for oven workers whose tasks did not involve direct work at the oven site(2). Benzo(a)pyrene was detected in air samples (taken at breathing height using personal sampling pumps) of 6 workers in a plant producing carbon anodes for aluminum electrolysis, worksite - concn of benzo(a)pyrene (ug/cu m): forming section - 0.89 to 3.12; paste plant - 1.37 to 4.43; store section (broken green anodes and burned anodes) - 0.16 to 0.79; forming section - 2.12 to 4.88; store section (coke) paste plant - 0.17 to 2.03; and all worksites - 0.27 to 3.66(3). Benzo(a)pyrene has been detected in occupational environments at the following airborne concns

(geometric mean), ug/cu m: coke plant, 8.02; carbon anode plant, 1.155; graphite plant, 0.083; silicon carbide plant, 0.036; metal recycling plant, 0.014; and a bitumen paving plant, 0.010(4). Air sampled from the breathing zone of chimney sweeps during dirty work contained benzo(a)pyrene at concns ranging from 0.36 to 0.82 ug/cu m(5). Personal air samples collected at a new Finnish coking plant between 1988 and 1990 contained BaP concns of 1.4-2.5 ug/cu m (the highest mean concns were found among gas workers, at 6.0-10.3 ug/cu m); stationary air samples detected BaP at concns from < 0.01 to 31.15 ug/cu m(6). Air samples collected above the doors of smoking kilns used in Danish smokehouses contained benzo(a)pyrene in the particulate phase at a maximum concn of 78 ug/cu m(7).[(1) Gressel MG et al; Appl Ind Hyg 3: 11-17 (1988) (2) Petry T et al; Ann Occup Hyg 38: 741-52 (1994) (3) Petry T et al; Ann Occup Hygiene 40: 345-57 (1996) (4) Petry T et al; Chemosphere 32: 639-48 (1996) (5) Knecht U et al; Br J Ind Med 46: 47982 (1989) (6) Yrjanheikki E et al; Am Ind Hyg Assoc J 56: 782-7 (1995) (7) Nordholm L et al; Scand J Work Environ Health 12: 614-18 (1986)] **PEER REVIEWED** The benzo(a)pyrene concn generated from heating 100 g cooking oil to 270 deg C by a controlled electronic heater in a Chinese laboratory chamber is (ug/cu m): 0.22 for soybean oil, 0.12 for peanut oil, 0.06 for sunflower oil, 0.07 for lard oil, 0.11 for corn oil, 0.28 for mustard oil, and 0.41 for edible mixture oil(1). The concns of benzo(a)pyrene from 1 g tobacco (generated in a chamber by a smoking machine with a 2 second puff duration, 20 mL puff volume, and 1 puff per minute) in the following Chinese brands of cigarettes were (ug/cu m), 0.13 in Honghe, 0.01 in Hengda, 0.02 in Xili, 0.07 in Jinqiao, 0.09 in Zhongnanhai, 0.10 in Blackgold, and 0.18 in Greatwall(1).[(1) Zhang L et al; Chemosphere 75: 453-61 (2009)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/19200570?dopt=Abstract" target=new>PubMed Abstract Benzo(a)pyrene was detected in 35 urban (from London and Birmingham) and 39 suburban air samples collected for 24 consecutive hours by non-smoking volunteers wearing air sampling pumps, at total arithmetic mean (range) concns of 0.19 (not detected to 1.19), and 0.16 (not detected to 0.80) ng/cu m, respectively(1). Benzo(a)pyrene was detected in 17 rural air samples collected from Wales and West Midlands, UK, by non-smoking volunteers wearing air sampling pumps for 24 consecutive hours, at arithmetic mean (range) concns of 0.79 (0.02-5.36), and 0.15 (0.01-0.37) ng/cu m, respectively(1).[(1) Saborit JMD et al; Environ Sci Technol 43: 4582-8 (2009)] **PEER REVIEWED** BODY BURDEN: Milk of nursing mothers was analyzed for the presence of benzo(a)pyrene. Levels of 7.6 to 387 ng/mL (with the mean value of 129.5 ng/mL) were found in sample of ten nursing mothers. Blood samples taken from 56 children (aged 2-12 years) in and near Lucknow, India in September 2005 to August 2006, contained benzo(a)pyrene at a median concn of 1.4 ppb(2).[(1) Health &amp; Welfare Canada; Polycyclic Aromatic Hydrocarbons p.38 (1979) Report No. 80-EHD-50 (2) Singh VK et al; Arch Environ Contam Toxicol 54: 348-54 (2008)] **PEER REVIEWED** AVERAGE DAILY INTAKE: Benzo(a)pyrene air intake: 0.010 to 0.044 ug/day(1); (assume avg conc of 0.9 ng/cu m)(2) 0.18 ng; BaP water intake: 0.001 ug/day; benzo(a)pyrene food intake: 0.16 to 1.6 ug/day(1); (assume avg concn of 0.15 ug/kg)(2) 0.24 ug(SRC). The report of Czech Statistical Office, 2003, estimated the dietary daily intake of benzo(a)pyrene via fruits and vegetables in the Czech Republic (ng/day) are: apple, 2.3; apricot, 0.5; cauliflower, 0.4;

cabbage, 0.1; cucumber, 0.5; grape, 0.8; parsley, 0.1; and tomato, 1.0(3).[(1) Vaessen HAMG et al; Toxicol Environ Chem 16: 281-94 (1988) (2) Menzie CA et al; Environ Sci Technol 26(7): 1278-84 (1992) (3) Janska M et al; Bull Environ Contam Toxicol 77: 492-9 (2006)] **PEER REVIEWED** NATURAL POLLUTION SOURCES: Benzo(a)pyrene occurs naturally in crude oils, shale oils, and coal tars, and is emitted with gases and fly ash from active volcanoes(1). There is some evidence for biosynthesis by plants(2), bacteria and algae(3). Benzo(a)pyrene occurs in fossil fuels(4). Benzo(a)pyrene is a component of the condensate isolated from Citrullus colocynthis (coloquint) seeds(5). Emissions of polycyclic aromatic hydrocarbons, including benzo(a)pyrene, are a product of incomplete combustion of organic matter(6).[(1) Warshawsky D; Patty's Toxicology. (2007). NY, NY: John Wiley &amp; Sons, Inc. Polycyclic and Heterocyclic Aromatic Hydrocarbons. On-line posting date: December 4, 2000. (2) Sims RC, Overcash MR; Res Rev 88: 1-68 (1983) (3) Verschueren K; Handbook of Environmental Data on Organic Chemicals. 3rd ed NY,NY: Von Nostrand Reinhold pp. 290-302 (1996) (4) IARC; Polynuclear Aromatic Hydrocarbons Part I Chem and Environ Data 32: 211-24 (1983) (5) Habs M et al; J Cancer Res Clin Oncol 108 (1): 154-6 (1984) (6) ATSDR; Toxicological Profile for Polycyclic Aromatic Hydrocarbons. Atlanta, GA: Agency for Toxic Substances and Disease Registry, US Public Health Service (1995)] **PEER REVIEWED** Benzo(a)pyrene has been produced by pyrolysis of anthracene at 950 deg C, of dicetyl at 800 deg C, of carbohydrates, amino acids and fatty acids at 700 deg C and at 500 deg C, of different tobacco constituents at 650 deg C, of aliphatic hydrocarbons, 340 mg/kg at 800 deg C; found in pyrolysis products of agar-agar, natural dyes, humectants, glues, starches and logwood(1).[(1) IARC; Certain Polycyclic Aromatic Hydrocarbons and Heterocyclic Compounds 3: 91-136 (1973)] **PEER REVIEWED** ARTIFICIAL POLLUTION SOURCES: Air pollution from motor transport exhaust gases was studied in Kazan, Russian SFSR, USSR, in 1974-1977. In the central part of town, where motor transport movement was most intense, the concn of CO, NOx and benz(a)pyrene in the air was higher than in new industrial regions. There was a direct relationship between concentrations of these substances and the intensity of motor transport flow. ...[Dauton FF; Kazan Med Zh 61 (3): 61-3 (1980)] **PEER REVIEWED** There is no commercial production or known use for benzo(a)pyrene; it occurs ubiquitously as a product of incomplete combustion(1). It has been identified in mainstream cigarette smoke; sidestream cigarette smoke; smoke of cigars; mainstream smoke of marijuana cigarettes; gasoline engine exhaust; diesel engine exhaust; various crude oils; various fresh and used motor oils; gasolines; charcoal-broiled steaks; various processed foods; various oils, margarine, butter, fats; fruits, vegetables, and cereals; roasted coffee; and tea(1).[(1) IARC; Polynuclear Aromatic Hydrocarbons Part I Chem and Environ Data 32: 211-24 (1983)] **PEER REVIEWED** Cigarette smoke and tar contain up to 0.1% benzo(a)pyrene, pyrolyzed from isoprene and C6 to C10 alkylbenzene precursors. The gasoline engine emits up to 0.170 ng of benzo(a)pyrene per gallon of fuel but only 0.02 to 0.03 ng/gal in an emission-controlled vehicle. The greatest emissions occur from residential energy production in coal and wood furnaces, mounting to tons of benzo(a)pyrene per year in the US. Other sources represent industrial coke-oven emissions and road abrasions(1).[(1) Warshawsky D; Patty's Toxicology. (2007). NY, NY: John Wiley &amp; Sons, Inc., Polycyclic and Heterocyclic Aromatic Hydrocarbons. On-line posting date:

December 4, 2000.] **PEER REVIEWED** ENVIRONMENTAL FATE: TERRESTRIAL FATE: Based on a classification scheme(1), measured soil Koc values ranging from 930 to 6,300(2,SRC), indicate that benzo(a)pyrene is expected to have low to no mobility in soil(SRC). Volatilization of benzo(a)pyrene from moist soil surfaces is not expected to be an important fate process(SRC) given a Henry's Law constant of 4.57X10-7 atm-cu m/mole(3). Benzo(a)pyrene is not expected to volatilize from dry soil surfaces(SRC) based upon an extrapolated vapor pressure of 5.49X10-9 mm Hg at 25 deg C(4). The persistence of benzo(a)pyrene in soil is expected to vary depending upon the nature of compounds accompanying it and the nature and previous history of the soil(5); biodegradation half-lives of 309 and 229 days were observed for benzo(a)pyrene in Kidman and McLaurin sandy loam soils, respectively(6).[(1) Swann RL et al; Res Rev 85: 17-28 (1983) (2) Symons BD et al; JWPCF 60: 1684-93 (1988) (3) Ten Hulscher TEM et al; Environ Toxicol Chem 11: 1595-603 (1992) (4) Murray JJ et al; Can J Chem 52: 557-63 (1974) (5) Goodin JD, Webber MD; J Environ Qual 24: 271-8 (1995) (6) Park KS et al; Environ Toxicol Chem 9: 187-95 (1990)] **PEER REVIEWED** AQUATIC FATE: Based on a classification scheme(1), measured Koc values from sediments and porewaters ranging from 2.7X10+5 to 1.9X10+6(2,3), indicate that benzo(a)pyrene is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(4) based upon a Henry's Law constant of 4.57X10-7 atm-cu m/mole(5). According to a classification scheme(6), measured BCF values of 8.7 to 1X10+5(7,8), suggests the potential for bioconcentration in aquatic organisms can be low to very high(SRC). Biodegradation of benzo(a)pyrene is expected to be a slow fate process(SRC); the removal of 64% of benzo(a)pyrene over 36 days in an activated sludge pilot reactor was attributed to biodegradation(9).[(1) Swann RL et al; Res Rev 85: 17-28 (1983) (2) Gert-Jandemaagd P et al; Polycyclic Aromat Compd 5: 219-24 (1994) (3) McGroody SE, Farrington JW; Environ Sci Technol 29: 1542-50 (1995) (4) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 15-1 to 15-29 (1990) (5) Ten Hulscher TEM et al; Environ Toxicol Chem 11: 1595-603 (1992) (6) Franke C et al; Chemosphere 29: 1501-14 (1994) (7) Anderson JW et al; Sources, Fates, and Effects of Aromatic Hydrocarbons in the Alaskan Marine Environment with Recommendations for Monitoring Strategies. NTIS PB86-168-291/AS. Washington, DC: USEPA (1986) (8) Meador JP et al; Rev Environ Contam Toxicol, Vol 143, Springer-Verlag: New York, NY (1995) (9) Smith JR et al; Water Environ Res 65: 804-18 (1993)] **PEER REVIEWED** ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), benzo(a)pyrene, which has an extrapolated vapor pressure of 5.49X10-9 mm Hg at 25 deg C(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase benzo(a)pyrene may be removed from the air by wet or dry deposition(SRC). Benzo(a)pyrene contains chromophores that absorb at wavelengths > 290 nm(3) and therefore is expected to be susceptible to direct photolysis by sunlight(SRC); after 17 hours irradiation with light > 290 nm, 26.5% of BaP adsorbed onto silica gel was degraded(4).[(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988) (2) Murray JJ et al; Can J Chem 52: 557-63 (1974) (3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 8-12 (1990) (4) Freitag D et al; Chemosphere 14: 1589-616 (1985)] **PEER REVIEWED** ENVIRONMENTAL BIODEGRADATION:

AEROBIC: (14)C-benzo(a)pyrene was not significantly mineralized in sludge treated Caledon soil; half-lives ranged from 23 to 266 weeks(1). The persistence of benzo(a)pyrene in soil is expected to vary depending upon the nature of compounds accompanying it and the nature and previous history of the soil(1). After 5 days incubation in activated sludge, < 0.1% of the applied (14)C-benzo(a)pyrene concn was degraded to (14)-CO2(2). Incubation of (14)C-benzo(a)pyrene in creosote-pentachlorophenol contaminated soil over 285 days led to a small, < 1%, mineralization of benzo(a)pyrene(3). Calculated half-lives for the mineralization of (14)C-benzo(a)pyrene in sediment/water microcosms ranged from > 200 weeks in Redfish Bay, TX to > 300 weeks in Lake Chicot, AR; no mineralization was detected in microcosms containing sediment and water from DeGray Reservoir, AR(4). The extent of mineralization of (14)C-benzo(a)pyrene, at a concentration of 105 ng/g, in soils collected from an abandoned coal tar refinery was very low, < 8%, after 160 days(5). The level of indigenous mineralization of (14)C-benzo(a)pyrene in soils obtained from three abandoned coal gasification plants as measured by serum bottle respirometry ranged from not detectable to 25% following incubations > 180 days; (14)C-benzo(a)pyrene mineralization occurred after a 28-day lag period(6). In soils from Alert (contaminated with Arctic diesel fuel), Saglek (from a radar installation), Varta (from a former gasworks site), and Westbrook (not known to be polluted), the percent removal of benzo(a)pyrene (10 ug/mL concn) from enrichment cultures after 90 days incubation under aerobic conditions were, respectively: at 20 deg C, 68, 76, 60, and 27; at 7 deg C, 33, 31, 34 and 37(7).[(1) Goodin JD, Webber MD; J Environ Qual 24: 271-8 (1995) (2) Freitag D et al; Chemosphere 14: 1589-616 (1985) (3) Sims RC, Abbott CK; Evaluation of Mechanisms of Alteration and Humification of PAHS for Water Quality Management, USGS/G-172 (NTIS PB93-118313) Logan, UT: Utah Cent Water Resour Res (1992) (4) Heitkamp MA, Cerniglia CE; Environ Toxicol Chem 6: 535-46 (1987) (5) Grosser RJ et al; Environ Toxicol Chem 14: 375-82 (1995) (6) Grosser RJ et al; Appl Environ Microbiol 57: 3462-9 (1991) (7) Eriksson M et al; Appl Environ Microbiol 69: 275-84 (2003)] **PEER REVIEWED** AEROBIC: In a 240 day soil microcosm study, half-lives of 530, 290, and 220 days at 10, 20, and 30 deg C, respectively, were estimated for benzo(a)pyrene(1). In a pilot biotreatability study, benzo(a)pyrene was reduced 99.9% by a sequencing batch reactor(2). In soil-water slurry systems, with actual town gas soil, benzo(a)pyrene was biodegraded approximately 22% after 5 weeks incubation using a polycyclic aromatic hydrocarbon-acclimated mixed culture(3). In bench-scale biotreatability studies using a solid-phase bioremediation process (landfarming chambers containing sediment and soil collected from the American Creosote Works Superfund site, Pensacola, FL), the benzo(a)pyrene concn was reduced from 84.3 to 63.6 in unamended surface soil; 84.3 to 47.7 in nutrient-amended surface soil; 246.6 to 183.6 in unamended sediment; and 246.6 to 178.8 mg/L and farming chamber in nutrient-amended sediment following 12 weeks incubation(4). In shake flask studies, an initial benzo(a)pyrene concn of 2.1 ug/mL was reduced to 0.9 ug/ml following 2 weeks incubation in contaminated groundwater inoculated with indigenous soil microorganisms from the American Creosote Works Superfund site, Pensacola, FL(5). After 60 days of batch slurry bioremediation, the initial solid-phase benzo(a)pyrene concn of 56 ug/g was reduced to 25.2 ug/g, a 55% removal(6). In a soil column study containing sandy soil samples from a site contaminated with creosote, an initial benzo(a)pyrene concn of approximately 120 mg/kg was reduced to about 100 mg/kg following 170 days incubation(7). Half-lives derived for benzo(a)pyrene in four soils amended with sewage sludge ranged from 120 to 270 days, with a mean half-life of 211 days(8). 64% benzo(a)pyrene removal over 36 days in an activated

sludge pilot reactor was attributed to biodegradation(9). No significant degradation of benzo(a)pyrene was observed in soil obtained from a former tar-oil refinery following 8 weeks of incubation in a percolator(10). In soil classified as an Orthic Luvisol ( > 70% silt, > 20% clay), benzo(a)pyrene declined from the applied 10.8 to 4.3 mg/kg in 27.5 months; the soil half-life was determined to be 2.7 years(11). Mean estimated half-lives for sludge applied benzo(a)pyrene to Lee Valley and Luddington, UK soils were 3.2 and 8.2 years, respectively; biodegradation is suspected to be the most important loss process in these soils(12). Biodegradation rates of benzo(a)pyrene in Boston Harbor sediments ranged from 0.15 to 49.5 ng/h g; these values correspond to turnover rates of 53.7 to 82.3 days(13). Biodegradation half-lives of 309 and 229 days were observed for benzo(a)pyrene in Kidman and McLaurin sandy loam soils, respectively(14).[(1) Coover MP, Sims RC; Haz Waste Haz Mat 4: 69-82 (1987) (2) Bleam RD, Cawthray MK; Int Conf Physicochemical Biol Detoxif Hazard Wastes 2: 867-82 (1989) (3) Srivastava VJ et al; Proc Ind Waste Conf 44: 49-60 (1990) (4) Mueller JG et al; Environ Sci Technol 25: 1045-55 (1991) (5) Mueller JG et al; Appl Environ Microbiol 57: 1277-85 (1991) (6) Castaldi FJ; pp. 99-108 in Appl Biotechnol Site Remed, Hinchee RE et al eds, Ann Arbor, MI: Lewis Publ (1994) (7) Breedveld GD, Briseid T; pp. 204-212 in Appl Biotechnol Site Remed, Hinchee RE at al eds. Ann Arbor,MI: Lewis Publ (1994) (8) Wild SR, Jones KC; Environ Toxicol Chem 12: 5-12 (1993) (9) Smith JR et al; Water Environ Res 65: 804-18 (1993) (10) Weissenfels WD et al; Appl Microbiol Biotechnol 36: 689-96 (1992) (11) Doick KJ et al; Environ Sci Technol 39: 3663-70 (2005) (12) Wild SR et al; Contaminated Soil, Arendt F et al, eds (1990) (13) Shiaris MP; App Environ Microbiol 55: 1391-9 (1989) (14) Park KS et al; Environ Toxicol Chem 9: 187-95 (1990)] **PEER REVIEWED** ANAEROBIC: After 1 month incubation, approximately 25% biodegradation of BaP was observed in contaminated soils under anaerobic conditions(1). Anaerobic sludge digestion over a period of 32 days was found to have no statistically significant effect on the concn of benzo(a)pyrene(2). In soils from Alert (contaminated with Arctic diesel fuel), Saglek (from a radar installation), Varta (from a former gasworks site), and Westbrook (not known to be polluted), the percent removal of BaP (10 ug/mL concn) from enrichment cultures after 90 days incubation under anaerobic conditions were, respectively: at 20 deg C, 10, 10, 26, and 23; at 7 deg C, 26, 22, 6 and 3(3).[(1) Srivastava VJ et al; Proc Ind Waste Conf 44: 49-60 (1990) (2) Kirk PWW, Lester JN; Environ Technol 12: 13-20 (1990) (3) Eriksson M et al; Appl Environ Microbiol 69: 275-84 (2003)] **PEER REVIEWED** ENVIRONMENTAL ABIOTIC DEGRADATION: Data for the oxidation rates of benzo(a)pyrene coated on quartz surface and exposed to ozone or sunlight are presented; from about eight products detected in these experiments, three have been identified as quinones based on UV-absorption spectrometry and mass spectrometry(1). After 30 minutes exposure to gaseous dinitrogen pentoxide, benzo(a)pyrene deposited on glass-fiber filters gave significant yields of nitro derivatives; 6-nitrobenzo(a)pyrene was the main isomer formed, the 1 and 3 isomers were formed in much lower yields(2). Benzo(a)pyrene was more resistant to photochemical transformation when adsorbed onto eight stack ashes from coal burning (-4 to 53% change) than when adsorbed onto alumina, silica gel, or controlled-porosity glass (60,93, and 96% change, respectively)(3). The photolysis half-life of BaP in solution containing 50 uM riboflavin was 5 minutes, compared to 98 minutes in the absence of riboflavin; the half-life was 10.6 and 43.1 minutes when exposed to visible range of natural sunlight and UVA irradiation, respective(4). The photolysis half-life of benzo(a)pyrene on spruce needle surfaces exposed

to full sunlight in Munich, Germany in July 2001 was 33 hours(5).[(1) Rajagopalan R et al; Sci Total Environ 27: 33-42 (1983) (2) Pitts JN Jr et al; Environ Sci Technol 19: 1115-21 (1985) (3) Yokley RA et al; Environ Sci Technol 20: 86-90 (1986) (4) Zhao X et al; Chemosphere 63: 1116-23 (2006) (5) Niu J et al; Environ Pollut 123: 39-45 (2003)] **PEER REVIEWED** Half-lives of benzo(a)pyrene exposed to 0.19, 0.70, and 2.28 ppm ozone were 0.62, 0.4, and 0.3 hours, respectively; half-lives of benzo(a)pyrene exposed to 0, 0.19, 0.70, and 2.28 ppm ozone and irradiated with a Quartz line lamp, 290 to 400 nm, were 5.3, 0.58, 0.2, and 0.08 hours, respectively(1). Irradiation of benzo(a)pyrene adsorbed onto silica gel, alumina, fly ash, and carbon black, with a mercury vapor lamp yielded photolysis half-lives of 4.7, 1.4, 31, and 570 hours, respectively(2), indicating adsorption may affect photodegradation(SRC). Dark-corrected photolysis half-lives for benzo(a)pyrene adsorbed onto fly ash and irradiated with a mercury vapor lamp ranged from 28 to 805 hours; dark-corrected photolysis half-lives for benzo(a)pyrene adsorbed onto silica gel and alumina were 2.7 and 1.0 hours, respectively(3). Half-lives for the direct photochemical decomposition of benzo(a)pyrene in freshwater were computed to be: 0.54 hours near the surface of freshwater (simulated latitude, 40 deg N, mid-day, mid-summer); 3.2 hours at a depth of 5 m; and 13 hours at a depth of 5 m and partitioned to bottom sediment(4). After 17 hours irradiation with light > 290 nm, 26.5% of BaP adsorbed onto silica gel was degraded(5). A near-surface direct photolysis half-life of 32 minutes was observed for benzo(a)pyrene in water in the summer at 40 deg N latitude(6). Photolysis of (14)C-benzo(a)pyrene in methanolic solution with or without 0.1 M hydrogen peroxide under either UV light (300 nm) or natural sunlight transformed benzo(a)pyrene to polar materials subject to increased mineralization(7). After 2 hours irradiation at 300 nm, over 68% of the benzo(a)pyrene remained in methanol solution; 0.1 M hydrogen peroxide greatly enhanced the rate of degradation (half-life decreased to 20 min)(7). Half-lives of benzo(a)pyrene adsorbed onto clean glass-fiber filters and two dust loaded filters (0.23 and 0.69 mg/sq cm) and exposed to a UV lamp were 37, 199, and 428 minutes, respectively(8). A photolysis half-life of 0.48 hours was measured for benzo(a)pyrene in pure water following exposure to mid-summer sunlight; in coal-oil saturated water, the half-life increased to 5 hours(9). Benzo(a)pyrene is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(10). Benzo(a)pyrene contains chromophores that absorb at wavelengths > 290 nm(10) and therefore is expected to be susceptible to direct photolysis by sunlight(SRC).[(1) Lane DA, Katz M; Adv Environ Sci Technol 8: 137-54 (1977) (2) Behymer TD, Hites RA; Environ Sci Technol 19: 1004-6 (1985) (3) Behymer TD, Hites RA; Environ Sci Technol 22: 1311-9 (1988) (4) Anderson JW et al; Sources, Fates, and Effects of Aromatic Hydrocarbons in the Alaskan Marine Environment with Recommendations for Monitoring Strategies. NTIS PB86-168-291/AS. Washington,DC: USEPA (1986) (5) Freitag D et al; Chemosphere 14: 1589-616 (1985) (6) Zepp RG; pp. 69-110 in Dynamics Exposure and Hazard Assessment of Toxic Chemicals. Haque R, eds Ann Arbor,MI: Ann Arbor Sci (1980) (7) Miller RM et al; Appl Environ Microbiol 54: 1724-30 (1988) (8) Valerio F et al; Intern J Environ Chem 38: 343-9 (1990) (9) Picel KC et al; Polynucl Aromat Hydrocarbons. Cooke, Dennis eds. Battelle Press. 8: 1013-28 (1985) (10) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5, 8-12 (1990)] **PEER REVIEWED** Exposure of benzo(a)pyrene adsorbed on calcite to white fluorescent light. Half-life is dependent on the production of oxygen. Half-life: 11 hrs in an atmosphere of oxygen. /From table/[Castegnaro, M., G. Grimmer, O.

Hutzinger, W. Karcher, H. Kunte, M. LaFontaine, E.B. Sansone, G. Telling, and S.P. Tucker (eds.). Laboratory Decontamination and Destruction of Carcinogens in Laboratory Wastes: Some Polycyclic Aromatic Hydrocarbons. IARC Publications No. 49. Lyon, France: International Agency for Research on Cancer, 1983., p. 47] **PEER REVIEWED** ENVIRONMENTAL BIOCONCENTRATION: Gillichthys mirabilis (mudsucker) exposed to benzo(a)pyrene /concn not specified/ for 96 hr exhibited a bioconcentration factor of 0.048; Oligocottus maculosus (tidepool sculpin) exposed to benzo(a)pyrene /concn not specified/ for 1 hr exhibited a bioconcentration factor of 0.13; Citharichthys stigmacus (sand dab) exposed to benzo(a)pyrene /concn not specified/ for 1 hr exhibited a bioconcentration factor of 0.02. /Edible tissue/[Lee RG et al; Mar Biol 17: 201 (1972) as cited in USEPA; Ambient Water Quality Criteria Doc: Chloroalkyl Ethers p.B-4 (1980) EPA 440/5-80-030] **PEER REVIEWED** In the absence of dissolved humic material in water, benzo(a)pyrene was rapidly accumulated by bluegill sunfish during a 48-hour exposure period and then quickly biotransformed to polar and nonpolar metabolites (BCF = 2,657; this BCF reflects the steady-state level of both benzo(a)pyrene and metabolites); dissolved humic material in water reduced the accumulation by 90% (BCF = 225 to 301)(1). According to a classification scheme(2), these BCF values suggest the potential for bioconcentration in aquatic organisms is high to very high(SRC). After 3 days exposure to (14)C-benzo(a)pyrene, a bioaccumulation factor (concentration of chemical in fish, ug/g/final concentration in water, ug/g) of 480 was measured in Golden ide(3).[(1) McCarthy JF, Jimenez BD; Environ Sci Technol 19: 1072-6 (1985) (2) Franke C et al; Chemosphere 29: 1501-14 (1994) (3) Freitag D et al; Chemosphere 14: 1589-616 (1985)] **PEER REVIEWED** A mean BCF of 55,000 was measured in Pontoporeia hoyi (Great Lakes amphipod)(1). Bioconcentration factors (ratio between tissue and sediment concentrations) of 13.8 and 0.7 were measured in Polychaete sp. and Capitella capitata(2). BCFs in the clam Macoma inquinata were 861 from 7 days exposure to 0.0004 ppm benzo(a)pyrene via the overlying water column and 0.09 from exposure to oil-contaminated sediments, 0.64 ppm benzo(a)pyrene, for 7 days(3). BCFs of 8.7, 240 and 190 were measured in the bivalve Rangia cuneata over a period of 1 day using a benzo(a)pyrene water concentration of 0.052, 0.030 and 0.030 ppm(3). The bioaccumulation of benzo(a)pyrene by Daphnia magna from five lake waters was inversely correlated with the dissolved organic carbon concentration of the waters(4). The BCF in Daphnia magna in artificial humus-free control water was approximately 3400; in lake waters having a DOC of 1.2, 4.6, 6.5, 6.6, and 20.3 mg C/L the BCFs were approximately 3400, 2600, 2200, 2300, and 500, respectively(4). BCFs for benzo(a)pyrene, based on dry weight, in mussels incubated in Port Phillip Bay, Australia ranged from 1.3X10+4 to 1.8X10+4 (in water with no direct source of hydrocarbons), 7.0X10+3 to 8.0X10+3 (in areas where the main sources of hydrocarbons is urban drainage), and 1.2X10+5 to 3.1X10+5 (in sites close to the discharge of a major oil refinery)(5). Mean benzo(a)pyrene concentrations in the amphipod Diporeia following 2 days exposure to sediment-sorbed polycyclic aromatic hydrocarbons were 32, 20, and 24 nmol/g for sediments aged 3, 60, and 150 days, respectively; following 28 days exposure, concentrations were 302, 202, and 151 nmol/g for sediments aged 3, 60, and 150 days, respectively(6). Mercenaria mercenaria, exposed to nine polycyclic aromatic hydrocarbons (including BaP) for 48 hours did not eliminate them over a 45-day depuration period, but maintained them at detectable levels(7).[(1) Eadie BJ et al; Chemosphere 11: 847-58 (1982) (2) Bayona JM et al; Chemosphere 23: 313-26 (1991) (3) Anderson JW et al; Sources,

Fates, and Effects of Aromatic Hydrocarbons in the Alaskan Marine Environment with Recommendations for Monitoring Strategies. NTIS PB86-168-291/AS. Washington,DC: USEPA (1986) (4) Okari A, Kukkonen J; Bull Environ Contam Toxicol 45: 54-61 (1990) (5) Murray AP et al; Mar Pollut Bull 22: 595-603 (1991) (6) Landrum PF et al; Environ Toxicol Chem 11: 1197-1208 (1992) (7) Tanacredl JT, Cardenas RR; Environ Sci Technol 25: 1453-61 (1991)] **PEER REVIEWED** A bioaccumulation factor (concn of chemical in algae, ug/g/final concentration in water, ug/g) of 3,300 in algae, Chlorella fusca, was measured after 1 day exposure to (14)C-benzo(a)pyrene(1). Average annual uptake and depuration rate constants at 4 deg C for benzo(a)pyrene in Pontoporeia hoyi (Great Lakes amphipod) were 116.8 mL/g hr and 0.0016/hour, respectively(2). Lumbriculus variegatus (freshwater oligochaete) accumulated sediment-associated (3)H-benzo(a)pyrene rapidly and achieved steady state within 96 to 168 hours; uptake clearance was 0.069 g sediment/g h(3). Elimination of (3)H-benzo(a)pyrene in clean sediment was rapid, but elimination in water was slower; elimination rate constants were 0.0229/hr for sediment and 0.0004/hr for water-only depuration(3). After 30 days exposure to (14)C-benzo(a)pyrene adsorbed onto sediment an initial uptake rate constant of 18/hr was measured in Brachydanio rerio (zebra fish); depuration half-lives relative to clean and contaminated water were 138 hours(4). In laboratory microcosms, benzo(a)pyrene was rapidly accumulated by Chironomus riparius (midge) incubated in sediments spiked with benzo(a)pyrene; mean concentrations in chironomids ranged from 12 ug/kg in controls to 6,030 ug/kg in benzo(a)pyrene treatments(5). A BCF (chemical concentration in tissue/free and bound chemical concentration in interstitial water) of approximately 1X10+5 was measured in the amphipod Rhepoxynius abronius after 10 days exposure to benzo(a)pyrene(6). Elimination half-lives of 16 and 4.8, 7, 21.7, and 8.0 days were measured in Mytilus edilus (blue mussels), Abarenicola pacifica (polychaete), Crassotrea virginica (Eastern oyster), and Mercenaria mercenaria (clam), respectively(6). Clams, Macoma nasuta, exposed to field-contaminated sediments for 28 days contained benzo(a)pyrene at mean concentrations ranging from 1.4 to 66 ng/g dry weight(7). The bioconcentration factor for total activity was measured for (14)C-benzo(a)pyrene at 1119 and 3068 in freshwater amphopods (Gammarus fossarun) and isopods (Asellus aquaticus), respectively(8).[(1) Freitag D et al; Chemosphere 14: 1589-616 (1985) (2) Landrum PF; Aquatic Toxicol 12: 245-71 (1988) (3) Kukkonen J, Landrum PF; Environ Toxicol Chem 14: 523-31 (1995) (4) Djomo JE et al; Environ Toxicol Chem 17: 1177-81 (1996) (5) Clements WH et al; Arch Environ Contam Toxicol 26: 261-6 (1994) (6) Meador JP et al; Rev Environ Contam Toxicol. NY,NY: Springer-Verlag 143: 79-165 (1995) (7) Ferraro SP et al; Arch Environ Contam Toxicol 19: 386-94 (1990) (8) Richter S, Nagel R; Chemosphere 66: 603-610 (2007)] **PEER REVIEWED** BCF (bioconcentration factor) Prionospio cirrifera and Spiochaetpoterus costarum (polychaete worms) = 13.8 /ratio of polychaeta dry wt to sediment dry wt/[Verschueren, K. Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. John Wiley &amp; Sons. New York, NY. 2001, p. 305] **PEER REVIEWED** BCF (bioconcentration factor) Capitella capitata (polychaete worm) = 0.7 /ratio of polychaeta dry wt to sediment dry wt/[Verschueren, K. Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. John Wiley &amp; Sons. New York, NY. 2001, p. 305] **PEER REVIEWED** SOIL ADSORPTION/MOBILITY: Sorption coefficients for benzo(a)pyrene obtained during 48 hour batch experiments using two lake sediments with organic carbon content of 1.87

and 2.07%, and a high chemical concentration were 7,000 and 22,000, respectively(1). Sorption coefficients obtained from 48 hour batch experiments using a low benzo(a)pyrene concentration were 8,700 and 35,000 using lake sediments with 1.87% and 2.07% organic carbon, respectively(1). These values correspond to estimated Koc values of 2.7X10+5, 1.1X10+6, 4.7X10+5, and 1.7X10+6(SRC) using a regression-derived equation(2).. Sorption removal accounted for > 3.0% and > 3.2% of the benzo(a)pyrene present in the influent of a high-loaded laboratory scale activated sludge reactor and a biological aerated filter reactor, respectively; the calculated adsorption removal may be conservatively low because the sludge samples were dried before analysis(3). Kd, soil/water partition coefficients, of 18.2 and 69.0 were determined in Kidman sandy loam, 0.51% organic carbon, and Nunn clay loam, 1.1% organic carbon(4). These values correspond to Koc values of 930 and 6300, respectively(SRC), using a regression-derived equation(2).. Measured log Koc values ranged from 6.00 to 6.28 in sediments and porewater isolated from three cores from Boston Harbor, MA(5). Sorption partition coefficients for benzo(a)pyrene with natural dissolved organic carbon from Lake Ketelmeer ranged from 2.8X10+6 at 45 deg C to 1.6X10+7 at 16 deg C(6). A sorption partition coefficient of 2.5X10+6 was observed for benzo(a)pyrene with particulate organic matter from Lake Ketelmeer at 20 deg C(6). Average partition coefficients for benzo(a)pyrene in natural interstitial waters ranged from 2.2X10+3 and 9.0X10+6 for Government Pond, Grand Haven, MI and Lake Michigan, respectively(7). Sorption of (14)C-benzo(a)pyrene on sediment collected in the harbor of Rotterdam was measured using batch experiments; cosolvent partition coefficients(log) ranged from 5.2 to 6.3(8). Partition coefficients (log) for (14)C-benzo(a)pyrene using fulvic and humic acids derived from salt-marsh estuaries ranged from 3.48 to 3.86 and 4.12 to 4.29, respectively(9). Benzo(a)pyrene log Kp values ranged from 5.18 to 5.79 in porewater and 4.90 to 5.36 in elutriates(10). 22% benzo(a)pyrene removal over 36 days in an activated sludge pilot reactor was attributed to adsorption to sludge(11). According to a recommended classification scheme(12), these Koc values suggest that benzo(a)pyrene is expected to have low to no mobility in soil(SRC).[(1) Gert-Jandemaagd P et al; Polycyclic Aromat Compd 5: 219-24 (1994) (2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington,DC: Amer Chem Soc pp. 4-2, 4-9 (1990) (3) Clapp LW et al; Water Environ Res 66: 153-60 (1994) (4) Symons BD et al; JWPCF 60: 1684-93 (1988) (5) McGroody SE, Farrington JW; Environ Sci Technol 29: 1542-50 (1995) (6) Luers F, Ten Hulscher TEM; Chemosphere 33: 643-57 (1996) (7) Landrum PF et al; Environ Toxicol Chem 4: 459-67 (1985) (8) Hegeman WJM et al; Environ Sci Technol 29: 363-71 (1995) (9) Alberts JJ et al; Mar Chem 28: 77-87 (1989) (10) Harkey GA et al; Chemosphere 28: 583-96 (1994) (11) Smith JR et al; Water Environ Res 65: 804-18 (1993) (12) Swann RL et al; Res Rev 85: 23 (1983)] **PEER REVIEWED** Sorption removal accounted for > 3.0% and > 3.2% of the benzo(a)pyrene present in the influent of a high-loaded laboratory scale activated sludge reactor and a biological aerated filter reactor, respectively; the calculated adsorption removal may be conservatively low because the sludge samples were dried before analysis(1). 22% benzo(a)pyrene removal over 36 days in an activated sludge pilot reactor was attributed to adsorption to sludge(2). Percentages of benzo(a)pyrene (relative to the total sorbed mass) released from different soot samples, coal and charcoal upon supercritical fluid extraction after 120 minutes, using mild conditions (50 deg C, 200 bar), mimicking desorption into contaminant-free water, was: wood soot, 0.8; coal soot, 25.8; oil soot and coal, < 1; and traffic soot and charcoal, < 0.5(3).[(1) Clapp LW et al; Water Environ Res 66: 153-60 (1994) (2) Smith JR et al; Water Environ Res 65: 804-18 (1993) (3) Jonker MTO et al; Environ Sci Technol 39: 7889-95 (2005)]

**PEER REVIEWED** VOLATILIZATION FROM WATER/SOIL: The Henry's Law constant for benzo(a)pyrene is 4.57X10-7 atm-cu m/mole(1). This Henry's Law constant indicates that benzo(a)pyrene is expected to be essentially nonvolatile from water surfaces(2). Benzo(a)pyrene's Henry's Law constant indicates that volatilization from moist soil surfaces may not occur(SRC). Benzo(a)pyrene is not expected to volatilize from dry soil surfaces(SRC) based upon an extrapolated vapor pressure of 5.49X10-9 mm Hg(3).[(1) Ten Hulscher TEM et al; Environ Toxicol Chem 11: 1595-603 (1992) (2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 15-1 to 15-29 (1990) (3) Murray JJ et al; Can J Chem 52: 557-63 (1974)] **PEER REVIEWED** ENVIRONMENTAL WATER CONCENTRATIONS: GROUNDWATER: Benzo(a)pyrene was detected in 8% of groundwater samples from 4 wood treatment sites at an avg concn of 57 ppb(1). Unfiltered groundwater samples from a well depth of 21 m at a location adjacent to the American Creosote Works in Pensacola, FL in March 1990 were found to contain benzo(a)pyrene at a concn of 2.1 mg/L(2). Groundwater from 232 pumping stations in the Netherlands contained a maximum benzo(a)pyrene concn of 1 ppb(3). Samples of groundwater from 3 sites in Germany in 1963-64 contained 0.1 to 23.4 parts per trillion benzo(a)pyrene(4).[(1) Rosenfeld JK, Plumb RHJR; Ground Water Monit Rev 11: 133-40 (1991) (2) Middaugh DP et al; Arch Environ Contam Toxicol 21: 233-44 (1991) (3) Zoeteman BCJ et al; Sci Total Environ 21: 187-202 (1981) (4) Sorrell RK et al; Environ Internat 4: 245-54 (1980)] **PEER REVIEWED** DRINKING WATER: 87% of water samples from 15 USA cities contained benzo(a)pyrene at concns of 0.1 to 2.1 parts per trillion, avg 0.55 parts per trillion(1). Benzo(a)pyrene was detected in treated surface waters used as drinking waters (in parts per trillion): River Rhine, 0.5, Lake Constance, 1.7, English River, 9(1). In Germany in 1968, samples of groundwater and tap water contained benzo(a)pyrene at concns of 0.4-3.8 and 0.5-4.0 ug/cu m, respectively(2). Water samples from the rivers Gersprenz, Danube, Main, Aach and Schussen in Germany detected benzo(a)pyrene at concns of 9.6, 0.6, 1.1-43, 4-16, and 10 ng/L, respectively(2). Drinking water from the Netherlands contained an avg 2 parts per trillion benzo(a)pyrene, max 15 parts per trillion(3). In the UK between 1974 and 1975, 7 distributed treated surface water systems contained benzo(a)pyrene at trace to < 3 parts per trillion; in 8 groundwater distribution systems between 1974 and 1977, trace to < 10 parts per trillion, max during repair work on parts of 1 system, 101 parts per trillion(4). In Norway, 4 samples contained benzo(a)pyrene at < 0.05 to 0.29 parts per trillion(5).[(1) Santodonato J et al; Health and Ecological Assessment of Polynuclear Aromatic Hydrocarbons. Lee SD, Grant L, eds Park Forest South,IL: Pathotox Pub Inc. p 119-22 (1981) (2) Verschueren K; Handbook of environmental data on organic chemicals. 4th ed NY,NY: John Wiley &amp; Sons, Inc., p.301 (2001) (3) Kraybill HF; NY Aca Sci Ann 298: 80-9 (1977) (4) Crane RI et al; A Survey of Polycyclic Aromatic Hydrocarbon Levels in British Waters TR-158 Medmenham, UK: Water Research Centre p. 47 (1981) (5) Kveseth K et al; Chemosphere 11: 623-39 (1982)] **PEER REVIEWED** SURFACE WATER: Concns of dissolved and particulate benzo(a)pyrene in water samples collected from various sites in Port Phillip Bay, Australia in May and August 1986 ranged from 0.002-0.008 and 0.032-0.044 ng/L in water with no direct source of hydrocarbons, 0.015-0.021 and 0.018-0.027 ng/L in areas where the main sources of hydrocarbons is urban drainage, and 0.007-0.012 and 0.048-0.084 ng/L in sites close to the discharge of a

major oil refinery, respectively(1). The benzo(a)pyrene mean (max) concn (ug/L) detected in surface water of four rivers in Hangzhou, China, collected in July and November 1999-2002 were, respectively: Qiantang River, 3.575 (10.10), and 0.835 (2.785); Hangzhou Canal, 1.949 (6.640), and 0.402 (1.981); Inland River, 1.129 (6.686), and 1.314 (3.889); West Lake, 3.100 (10.22), and 0.349 (1.658)(2). Water samples collected from three drains, and from Lake Manzala, located at the northeastern edge of the Nile Delta in Egypt, contained benzo(a)pyrene at concns ranging from 31.0 to 460.0 ng/L(3). Water samples from four rivers in Germany contained 0.6 to 80 parts per trillion, avg 23 parts per trillion; 2 rivers in the USSR contained 17 and 10 parts per trillion; and water from 3 stations on the Thames River, UK, 0.13 to 0.35 ug/L, avg 0.21 ug/L benzo(a)pyrene(4). It was detected in water from 6 sites on 4 rivers in Germany between 1963-64 at 0.6-114.0 parts per trillion; from 5 sites in the USSR at < 0.1-13,000 parts per trillion; from 5 sites at Severn River in the UK at 1.5-13.5 parts per trillion; Thames River, 2 sites, 130-210 parts per trillion; River Trent and tributaries, 11 sites, 0.1-1.8 parts per trillion in solution; and in suspended solids (max River Trent at Keadby) at 0.8-504.0 parts per trillion(5). Benzo(a)pyrene was detected in 51 samples from 25 sites on 9 rivers in the UK between 1973-76 at 3.8 to 531 parts per trillion(6). BaP was detected in water samples collected from the Huaihe River, China, in summer 2002 at concns from 0.55 to 1.56 ug/L(7).[(1) Murray AP et al; Mar Pollut Bull 22: 595-603 (1991) (2) Zhu L et al; Chemosphere 56: 1085-95 (2004) (3) Badawy MI et al; Environ Contam Toxicol 55: 258-63 (1995) (4) Santodonato J et al; Health and Ecological Assessment of Polynuclear Aromatic Hydrocarbons. Lee SD, Grant L, eds Park Forest South,IL: Pathotox Pub Inc. p 119-20 (1981) (5) Sorrell RK et al; Environ Inter 4: 245-54 (1980) (6) Crane RI et al; A Survey of Polycyclic Aromatic Hydrocarbon Levels in British Waters TR-158 Medmenham,UK: Water Research Centre 47 pp (1981) (7) Huang H et al; Bull Environ Contam Toxicol 73: 339-46 (2004)] **PEER REVIEWED** SURFACE WATER: Benzo(a)pyrene was detected in suspended particulate matter samples collected in the St. Lawrence River and its tributaries in 1990 and 1991 at concns of 0.031 and 0.119 mg/kg, respectively(1). The concn of benzo(a)pyrene in Lake Superior water was 0.39 ng/L(2). Benzo(a)pyrene was detected in samples collected from the Otonabee River, Ontario, Canada in 1994 at concns ranging from 0.0080 to 0.0275 ug/mL(3). Mississippi river water samples collected between March-August 2004 detected benzo(a)pyrene at concns of 1.6-20.5 parts per trillion(4). Benzo(a)pyrene was detected in water samples from the Mississippi River at concns of 1 and 10 ng/L for samples collected near the inflow of the Ohio River and 20 miles below Memphis, TN, respectively(5). Benzo(a)pyrene was detected but not quantified in water and suspended sediment samples from Fort Erie and Niagara-on-the-Lake between December 1984 and March 1986(6). Benzo(a)pyrene has been reported in the following Great Lakes Basin ecosystems: Lake Ontario (Niagara River), Lake Erie (Union Ship Canal; Buffalo River; Smoke Creek; Cuyahago River; Rocky River), Lake Michigan (Muskegon River, St. Joseph River), and Lake Superior (St. Louis River, western basin)(7). In 1990 and 1992, the average benzo(a)pyrene concn in surface water (3 m depth) and bottom water (2 m above bottom) of the mesohaline Chesapeake Bay was 0.27 and 0.93 ng/L, respectively(8). US STORET Database reported that of surface water samples from 914 water stations, 2% contained benzo(a)pyrene at a median concn of < 10 ppb(9). Benzo(a)pyrene was detected in 9.4% of 85 water samples collected from 139 streams in 30 states during 1999 and 2000, at max and median concns of 0.24 and 0.04 ug/L, respectively(10).[(1) Pham T et al; Chemosphere 27: 1137-49 (1993) (2) Off RM et al; Atmos Environ 30: 3505-27 (1996) (3) Bennett ER et al; Chemosphere 33: 363-75 (1996) (4) Zhang S et al; Chemosphere 66: 1057-69 (2007) (5) Dalian IR et al; Chemosphere 15:

795-805 (1986) (6) Great Lakes Water Quality Board; Report to the International Joint Commission Vol II, Appendix B (1989) (7) Great Lakes Water Quality Board; Report to the Great Lakes Water Quality Board, Windsor, Ontario, Canada (1983) (8) Ko FC, Baker JE; Mar Chem 49: 171-88 (1995) (9) Staples CA et al; Environ Toxicol Chem 4: 131-42 (1985) (10) Kolpin DW et al; Environ Sci Technol 36: 1202-11 (2002)] **PEER REVIEWED** RAIN/SNOW: Benzo(a)pyrene was detected in the dissolved(and particulate) phases in snow, winter rain, spring rain, and summer rain samples collected at an urban site in Switzerland at mean concns of 3.7 (16); 2.4 (9.0); not detected (2.6); and not detected (3.2) ng/L, respectively; it was detected in the particulate phase of fog samples at a mean concn of 700 ng/L(1). Annual mean benzo(a)pyrene precipitation concns in Eagle Harbor, MI, Sleeping Bear Dunes, MI, Sturgeon Point, NY, and Point Petre, Ontario were 2.9, 3.8, 5.1, and 3.0 ng/L, respectively(2). Benzo(a)pyrene was detected in fog samples collected Sept to Dec 1986 in Dubendorf, a suburb of Zurich, Switzerland at concns ranging from 0.0 to 4.1 ng/ml; mean concn 1.2 ng/ml(3). Samples of rainwater collected from four locations in the Netherlands in 1983 were found to contain benzo(a)pyrene at median concns of 7, 16, 26, and 21 ng/L for Witteveen, de Bilt, Vlissingen, and Biest-houtakker, respectively(4). Benzo(a)pyrene has been detected in snow samples from urban, semi-rural Northeast Bavaria, Germany, urban Poznan, Poland, and urban Bayreuth, Germany at 29, 50, and 5 to 2000 ng/L, respectively(5). Benzo(a)pyrene has been detected in particulate matter associated with fog in urban Sheffield, Great Britain at a concn of 32.8 ug/100 cu m(5). Benzo(a)pyrene was detected in rainwater from the Netherlands during 2 rainfall events on 12/10/82 and 1 rainfall event in 9/83; in 3 samples taken 5, 12 and 23 min after onset of rain: 390, 9 and 6 parts per trillion, respectively; in 4 samples taken 8, 18, 27 and 38 min after onset of second rain event: 75, 25, 18 and not detected parts per trillion, respectively; in 8 samples taken 12 to 25 min after onset of rain: 10 to 37 parts per trillion(6). A surface snow sample collected at the Summit of the Greenland Ice Sheet in the summer of 1991 at a depth of 160 to 170 cm contained benzo(a)pyrene at a concn of 3.5 pg/kg(7).[(1) Leuenberger C et al; Atmos Environ 22: 695-705 (1988) (2) Off RM et al; Atmos Environ 30: 3505-27 (1996) (3) Capel PD et al; Atmos Environ 25A: 1335-46 (1991) (4) Den Hollander H et al; Sci Total Environ 52: 211-9 (1986) (5) Mazurek MA, Simoneit BRT; CRC Critical Review Environ Control Vol 16 pp 6-7 (1986) (6) VanNoort PCM, Wondergem; Environ Sci Technol 19: 1044-8 (1985) (7) Jaffrezo JL et al; Atmos Environ 28: 1139-45 (1994)] **PEER REVIEWED** SEAWATER: Seawater samples from the Baltic Sea collected in Nov 1993 at depths of 10 to 15 m were found to contain benzo(a)pyrene at concns ranging from 10.64 to 115.20 pg/L, average concn of 37.31 pg/L; concns in samples at depths below 70 m ranged from 5.00 to 71.36 pg/L, average concn of 28.38 pg/L(1). Benzo(a)pyrene was detected in water samples collected from three remote coastal and six offshore stations in the Baltic Sea; concns in the apparently dissolved fraction ranged from not detected to 5.7 ng/cu m, particle-associated benzo(a)pyrene ranged in concn from 1.6 to 70 ng/cu m(2). In the summer of 1987 to 1988, benzo(a)pyrene was detected in uncontaminated seawater samples from the Atlantic sector of the Southern Ocean at a mean concn of 0.1 ng/L and a maximum concn of 1.0 ng/L(3).[(1) Witt G; Mar Pollut Bull 31: 237-48 (1995) (2) Broman D et al; Environ Sci Technol 25: 1850-64 (1991) (3) Crimps GC; Mar Pollut Bull 24: 109-14 (1992)] **PEER REVIEWED** EFFLUENT CONCENTRATIONS: Average benzo(a)pyrene concns associated with the solid phase in raw sewage, primary effluent, and secondary effluent from the Hamilton

Woodward plant, a conventional activated sludge treatment facility, were 13.3, 9.2, and 1.9 ug/g, respectively(1). Grab wastewater samples collected from a coke plant contained benzo(a)pyrene at total concns ranging from 80 to 82 ug/L in the ammonia still influent, 5.0 ug/L in the ammonia still effluent, and 4.7 to 4.8 ug/L in the biological oxidation effluent(2). Benzo(a)pyrene was detected in farmland ditch water at a mean concn of 0.10 ug/L and railway right-of-way ditch water at mean concns of 43 and 0.10 ug/L for ditches with and without utility poles, respectively(3). 4% of the National Urban Runoff Program's 86 samples from 15 cities contained benzo(a)pyrene at concns ranging from 1 to 10 ppb(4). Samples of urban runoff collected in Madrid contained benzo(a)pyrene at a mean annual concn of 1.1 ug/L(5). Samples from Bekkelaget Sewage Treatment Plant in Oslo, Norway, contained < 3 to 5 parts per trillion benzo(a)pyrene(6). US STORET Database, 2.3% of 1253 water stations contained benzo(a)pyrene at a median concn of < 10 ppb(7). Those industries with mean raw or treated wastewater concn exceeding 100 ppb include (max raw wastewater benzo(a)pyrene concn, ppb): coal mining (140), iron and steel manufacturing (14,000), nonferrous metals manufacturing (570), and timber products processing (2,700)(8). Industrial effluents detected benzo(a)pyrene in: shale oil, after dephenolization (2, 312 ppb); gasworks, after filtration through coke bed (20 ppb) and after dephenolization (290 ppb); coke by-products after biochemical treatment (12-16 ppb); oil refineries (0.05-5.0 ppb); wood preservative sludge (3.39 g/L raw sludge); domestic effluent (0.038-0.074 ppb); final effluent of sewage works (0.03 ppb); sewage (high percentage industry, 0.1-0.36 ppb); sewage during dry weather (0.001 ppb); sewage during heavy rain (1.84 ppb); primary and digested raw sewage sludge (0.27-0.57 ppm); liquors from sewage sludge heat-treatment plants (0.03-0.84 ppm); sludge cake from heat-treatment plants (0.31-0.52 ppm); storm runoff waters from M-6 motorway in the UK in 1986 (13 ng/L average)(9).[(1) Melcer H et al; Wat Environ Res 67: 926-34 (1995) (2) Walters RW, Luthy RG; Water Res 18: 795-809 (1984) (3) Wan MT; J Environ Qual 23: 1297-1304 (1994) (4) Cole RH et al; J Water Pollut Control Fed 56: 898-908 (1984) (5) Bomboi MT, Hernandez A; Water Res 25: 557-565 (1991) (6) Kveseth K et al; Chemosphere 11: 623-39 (1982) (7) Staples CA et al; Environ Toxicol Chem 4: 131-42 (1985) (8) USEPA; Treatability Manual; pp.1.10.5-1 to 1.10.5-4 USEPA-600/2-82-001A (1981) (9) Verschueren K; Handbook of Environmental Data on Organic Chemicals. 4th ed, John Wiley and Sons, Inc., NY: NY p 300-1 (2001)] **PEER REVIEWED** Benzo(a)pyrene was identified, not quantified, in emissions from a biomass gasifier(1). Benzo(a)pyrene was detected in emissions from a cast iron (sheet iron) wood stove burning different types of fuels, mg/cu m: virgin beech wood, 0.024 to 0.084 (0.118 to 0.688); briquettes made of wood chips, 0.177 to 0.281 (1.36 to 1.85); scrap wood, 0.191 to 0.652 (0.771 to 0.882); briquettes made of sorted domestic waste, 0.008 to 0.019 (0.059 to 0.262); pine wood preserved with pentachlorophenol, 0.298 to 0.760 (0.436 to 0.760); and rolled up newspapers, 0.036 to 0.055 (0.107 to 0.120)(2). Flue gases from a large incinerator plant in Italy contained benzo(a)pyrene at a concn of 4400 ng/normalized cu m(3). Benzo(a)pyrene was detected in 7.5% of water samples collected upstream, downstream, and from the effluent from 10 wastewater treatment plants in the US, at a median concn level below the reporting level of 0.5 ug/L, and a max concn of 0.084 ug/L(4). Benzo(a)pyrene was detected in 9.1% of 23 high-flow water samples collected up- and down-stream from 10 cities in Iowa in 2001, with a max concn of 0.06 ug/L; it was not detected in normal- and low-flow samples(5). In air samples collected between 1961 and 2004, benzo(a)pyrene was detected in 8 US vehicular traffic tunnels that were either directly presented as tailpipe emission factors in ug/vehicle-km or convertible to such a form; emissions for a tunnel fleet operating under

cruise conditions were highest prior to the 1980's and fell from > 30 ug/vehicle-km to approx 2 ug/km in the 1990's(6).[(1) Desilets DJ et al; Environ Sci Technol 18: 386-91 (1984) (2) Nielsen PA et al; Chemosphere 24: 1317-30 (1992) (3) Morselli L et al; Chemosphere 18: 2263-73 (1989) (4) Glassmeyer ST et al; Environ Sci Technol 39: 5157-69 (2005) (5) Kolpin DW et al; Sci Total Environ 328: 119-30 (2004) (6) Beyea J et al; Environ Sci Technol 42: 7315-20 (2008)] **PEER REVIEWED** Benzo(a)pyrene was detected in samples of sewage sludge collected February 2004-May 2005 from six waste-water treatment plants within Beijing City, China, with concns in five of the plants ranging from 226.73 to 585.48 ug/kg dry weight; a concn of 6174.17 ug/kg (above the max permitted content) was detected in the Wujiacun plant, where the sludge was collected from complicated wastewater discharged from steel and dyeing industry(1). The estimated annual emission rates (tons/yr) of BaP from the major anthropogenic sources in China in 2003 are: coking industry, 211; domestic coal, 204; industrial coal, 0.756; transport petroleum, 1.34; other petroleum, 0.521; straw, 2.60; firewood, 8.16; and aluminum production, 1.48(2). Benzo(a)pyrene was detected in wastewater sludge samples from 6 waste water treatment plants along the Nakdong River in Korea, at mean, median and range concns of 0.918, 0.126, and 0.032-4.93 mg/kg dry weight, respectively(3). BaP was detected in urban runoff in Hangzhou, China at concns from 0.184 to 0.268 ug/L, with a mean concn of 0.218 ug/L(4).[(1) Dai J et al; Chemosphere 66: 353-61 (2007) (2) Xu S et al; Environ Sci Technol 40: 702-8 (2006) (3) Ju J et al; Chemosphere 74: 441-7 (2009) (4) Zhu L et al; Chemosphere 56: 1085-95 (2004)] **PEER REVIEWED** SEDIMENT/SOIL CONCENTRATIONS: SEDIMENT: Benzo(a)pyrene was detected in suspended sediment samples taken from Suisun Bay, and Carquinez Strait (areas of San Francisco Bay, CA) in 1991 at average concns of 54.5 and 17.2 ng/g, respectively(1); bed and suspended sediment samples contained benzo(a)pyrene at concns ranging from 1.5-39 ng/g dry weight and 33-48 ng/g dry weigh, respectively(2). Surficial and surface water suspended solids sampled from Lake Superior contained benzo(a)pyrene at mean concns of 45.3 and 34 ng/g, respectively(3). Surficial sediments collected from St. Mary's River in 1985 contained benzo(a)pyrene at concns ranging from 0.11 to 48.0 mg/kg dry weight(4). Sediment samples collected from 5 regions of Casco Bay, Maine in Aug 1991 contained benzo(a)pyrene (concentration range, ppm dry weight): Inner Bay (43 to 741); West Bay (17 to 100); East Bay (50 to 498); Cape Small (1 to 433); and Outer Bay (62 to 209)(5). 95 of 96 grab samples from 19 stations in the Gulf of Maine collected in June and Sept 1983 contained benzo(a)pyrene at concns ranging from 2 to 33 ppb dry weight(6). Benzo(a)pyrene was detected in sediments from Eagle Harbor, Puget Sound, WA and President Point, WA at concns ranging from 190 to 2100 ng/g dry weight in Eagle Harbor and 41 ng/g dry weight in President Point sediment(7). Hamilton Harbor sediment cores collected in 1989 contained benzo(a)pyrene at concns ranges of, ug/g (depth in cm): 0.0 to 40.9 (0 to 2); 0.0 to 19.2 (2 to 4); and 2.2 to 22.1 (10 to 12)(8). Sediment cores collected from 17 locations on the Washington continental shelf and slope contained benzo(a)pyrene at concns of, ug/g organic carbon: inner shelf, 1.2 and 1.4; midshelf, 1.6 to 2.8; outer shelf, 0.5 and 1.2; slope, 0.2 to 1.1; and 22 to 24 cm (Pleistocene gray clay), 0.6(9). Benzo(a)pyrene was detected in sediment cores collected from the Lower Passaic River, NJ during Nov and Dec 1991 at concns ranging from 220 to 210,000 ug/kg dry weight(10). Bed sediments collected along a contamination gradient in the Lauritzen Canal, CA in 1993 contained benzo(a)pyrene at concns ranging from 150 to 1770 ng/g; the highest concn occurring at the head of the canal(11). 55% of the 31 sediment samples taken from the Detroit River in

1982 were found to contain benzo(a)pyrene at concns ranging from 0.12 to 17.64 mg/kg(12).[(1) Domagalski JL, Kuivila KM; Estuaries 16: 416-26 (1993) (2) Pereira WE et al; Mar Pollut Bull 24: 103-9 (1992) (3) Baker JE et al; Environ Sci Technol 25: 500-9 (1991) (4) Kauss PB, Hamdy YS; Hydrobiologia 219: 37-62 (1991) (5) Kennicutt MC II et al; Environ Sci Technol 28: 1-15 (1994) (6) Larsen PF et al; Mar Environ Res 18: 231-44 (1986) (7) Malins DC et al; Carcinogenesis 6: 1463-9 (1985) (8) Murphy TP et al; Water Pollut Res J Can 26: 1-16 (1991) (9) Prahl FG, Carpenter R; Est Coast Shelf Sci 18: 703-19 (1984) (10) Wenning RJ et al; Arch Environ Contam Toxicol 27: 64-81 (1994) (11) Pereira WE et al; Mar Environ Res 41: 299-314 (1996) (12) Great Lakes Water Quality Board; Report to the International Joint Commission Vol II, Appendix B (1989)] **PEER REVIEWED** SEDIMENT: Benzo(a)pyrene was detected in sediment cores collected along the "Golfe de Gascogne" continental shelf, France at concns ranging from < 0.1 to 52 ng/g dried sediment(1). Sediment cores from Lake Ketelmeer, a sedimentation area of the River Rhine contained benzo(a)pyrene at concns of 1.3 mg/kg in 1945, 2.0 mg/kg in 1965, and 0.7 mg/kg in 1985(2). Benzo(a)pyrene was detected in one sample of surficial sediments collected in Jan 1989 from the continental shelf of Tabasco state, Mexico at a concn of 735 ng/g dry weight(3). Benzo(a)pyrene was detected in sediments from the Danube and Traun rivers in Austria at concns ranging from 25 to 61 ug/kg dry weight and 20 to 22 ug/kg dry weight, respectively(4). Nearshore surface marine sediments from several locations in Australia contained benzo(a)pyrene at concns of, ug/kg dry weight: 170 to 1060, Brisbane River; 10 to 2600, Townsville Harbor; 820, Gladstone Harbor; 757, Greenwich Bay; 60 to 6800, Yarra River; 180 to 2000, Corio Bay; 20 to 60, Mallacoota Inlet; 0.6 to 4.4, Burdikin River; 2.7 to 39, Ross River; < 0.01, John Brewer Reef; < 0.1 to 2.6, Heron Island; and < 0.004 to 4.3, Green Island(5). In 1992, benzo(a)pyrene was detected in bed sediments from the San Joaquin River at Vernalis and Patterson at concns of 1.6 and 0.4 ng/L, respectively; it was detected in the bed and suspended sediments from tributaries at the following concns, ng/L, respectively: 0.6, 3.2 Salt Slough; 1.0, 1.4, Orestimba Creek; 76, 110 Dry Creek; 13, Mokelumne River at Woodbridge; 13, the Turlock Irrigation District lateral 5, and 3.5 in suspended sediments in San Joaquin River at Patterson(6). Sediment samples from 7 stations in Hor al-Hammar marsh contained benzo(a)pyrene at concns ranging from not detected to 0.09 ppb dry weight(7). Benzo(a)pyrene concns in sediment cores from Tilbury docks on the River Thames, UK were, ug/g dry sediment (depth below Ordnance Datum Newlyn, OD, is the mean sea level at Newlyn), cm): 1.28 (445-455), 1.62 (465-474), 1.67 (484-494), 1.53 (504-514), 1.97 (523-533), 1.57 (543-553), 1.48 (563-572), 1.89 (582-592), 3.38 (602-612), 3.95 (621-631), 4.37 (641-651), 3.61 (661-670), 3.02 (680-690), 3.15 (700-710), 2.97 (719-729), 3.86 (739-749), 2.56 (759-768), 3.80 (778-798), 3.59 (798-808), 4.15 (817-827), and 4.56 (837-847)(8). Surface sediments collected from the Baltic Sea in Oct and Nov 1993 were found to contain benzo(a)pyrene at concns ranging from 0.36 to 94.94 ng/g dry weight, mean 18.90, in sandy sediments and 67.90 to 209.57 ng/g dry weight, mean 121.32, in muddy sediments(9). Concns of benzo(a)pyrene in laminated sediments collected from the northern Baltic proper were, ug/g C (sediment layer, mm): 0.91 (0 to 1.8); 1.5 (1.8 to 3.6); 1.3 (3.6 to 5.4); 1.7 (7.2 to 9.0); 2.0 (10.8 to 12.6); 3.0 (16.2 to 18.0); 3.3 (21.6 to 23.4); 3.8 (27.0 to 28.8); 3.8 (32.4 to 34.2) and 3.0 (37.8 to 39.6)(10).[(1) Garrigues P et al; Int J Environ Anal Chem 28: 121-31 (1987) (2) Beurskens JEM et al; Water Sci Technol 29: 77-85 (1994) (3) Botello AV et al; Bull Environ Contam Toxicol 47: 565-71 (1991) (4) Chovanec A et al; Chemosphere 29: 2117-33 (1994) (5) Maher WA, Aislabie J; Sci Total Environ 112: 143-64 (1992) (6) Pereira WE et al; Environ Toxicol Chem 15: 172-80 (1996) (7) Al-Saad HT, Al-Timari

AA; Bull Environ Contam Toxicol 43: 864-9 (1989) (8) Taylor PN, Lester JN; Environ Technol 16: 1155-63 (1995) (9) Witt G; Mar Pollut Bull 31: 237-48 (1995) (10) Broman D et al; Chemosphere 29: 1325-31 (1994)] **PEER REVIEWED** SEDIMENT: Benzo(a)pyrene was detected in sediment samples taken in the vicinity of a chemical factory that processes crude tar and benzene in Czechoslovakia in Aug 1989; concns ranged from 595.2 to 2285.7 ng/g(1). 27 of 28 superlayer and underlayer deep sea sediment samples from 15 sampling sites in the Gulf of Lion, Mediterranean Sea, France were found to contain benzo(a)pyrene at concns ranging from 0.1 to 124.5 ng/g dry weight; the benzo(a)pyrene concn in a sediment sample from the Grand Rhone river, located downstream from a highly industrialized and urbanized area, was 514.8 ng/g dry sediment(2). Sediments from the Venice lagoon, a polluted coastal environment in northeastern Italy, contained benzo(a)pyrene at concns ranging from 1.1X10-2 to 9.3 ug/g dry sediment(3). The concn of benzo(a)pyrene in sediment cores taken near industrial plants on the St. Lawrence River in 1992 contained benzo(a)pyrene at concns of 307 and 0.43 ug/g near the Reynolds Aluminum plant and the General Motors plant, respectively(4). Benzo(a)pyrene was detected in suspended solids and sediment samples collected in summer 2002 from the Hauihe River, China, at concns of 0.16 to 1.03 ug/L and 0.14 to 0.17 mg/kg, respectively(5). Benzo(a)pyrene was detected in sediment samples from the Qiantang River, Hangzhou Canal, Inland River and West Lake in China at mean (range) concns of 4.611 (not detected-7.435), 297.8 (14.30-57.9), 58.37 (6.958-153.8), and 37.09 (23.96-62.88) ng/g dry weight, respectively(6).[(1) Holoubek I et al; Toxicol Environ Chem 29: 251-60 (1991)(2) Domine D et al; Sci Total Environ 155: 9-24 (1994) (3) LaRocca C et al; Ecotoxicol Environ Safety 33: 236-45 (1996) (4) Sokol RC et al; Environ Sci Technol 28: 2054-64 (1994) (5) Huang H et al; Bull Environ Contam Toxicol 73: 339-46 (2004) (6) Zhu L et al; Chemosphere 56: 1085-95 (2004)] **PEER REVIEWED** SEDIMENT: Benzo(a)pyrene was detected in ditch sediments adjacent to farmlands and railways in British Columbia, Canada, at mean concns of 0.10 and 0.68 ug/kg(1). It was detected in utility right-of-way ditch sediments at mean concns of, mg/kg wet weight: 67, at the base of utility poles; 0.11, 4 m upstream from a utility pole; 0.41, 0.1 to 0.3 m from a utility pole; and 0.64, 4 m downstream from a utility pole(1). Benzo(a)pyrene concns in nearshore coastal sediments offshore Matagorda, TX, near a multiwell platform averaged 9.4 ppb; in adjacent coastal estuaries the concn averaged 5.3 ppb(2). Sediment samples collected from Santa Monica Bay and Palos Verdes Shelf, CA in Sept 1985 contained mean benzo(a)pyrene concns of, ng/g dry weight (depth, cm): in the Bay 9.2 (0 to 2) and 4.7 (4 to 8); and in the Shelf 70 (0 to 2), 99 (8 to 12), 228 (0 to 2), and 440 (8 to 12)(3). The concn of benzo(a)pyrene in sediment cores taken from Arthur Kill, Hackensack River, and the Passaic River ranged from 0.31 to 11.0, 0.50 to 4.70, and 0.22 to 210 ng/kg, respectively(4). Benzo(a)pyrene was detected in marine (Saguenay Fjord, Quebec, Canada) and freshwater (St. Louis River, Quebec) sediment samples at mean concns of 0.040 and 0.840 ug/g dry weight, respectively(5). Benzo(a)pyrene was detected in Lake Erie sediments from one site in the western basin and another site just offshore of Cleveland, OH, at mean concns of 5.02 and 15.09 mg/kg, respectively; it was not detected in 5 other sites along the lake(6). Benzo(a)pyrene was detected in sediments from Quincy Bay in Boston Harbor and in the Hudson River in New York Harbor, at mean concns of 3200 and 500 ng/g dry weight, respectively(7).[(1) Wan MT; J Environ Qual 23: 1297-1304 (1994) (2) Brooks JM et al; Environ Sci Technol 24: 1079-85 (1990) (3) Ferraro SP et al; Arch Environ Contam Toxicol 19: 386-94 (1990) (4) Huntley SL et al; Bull Environ Contam Toxicol 51: 865-72 (1993) (5) Brion D, Pelletier E; Chemosphere 61: 867-76 (2005) (6) Debruyn JM et al;

Environ Sci Technol 43: 3467-73 (2009) (7) Lohmann R et al; Environ Sci Technol 39: 141-8 (2005)] **PEER REVIEWED** SEDIMENT: Benzo(a)pyrene was detected in sediments from 18 of 20 sites along Abu Qir bay, Egypt in 2004, at concns from 1.71 to 686.00 ng/g dry weight(1). Benzo(a)pyrene was detected in top sediments (0-5 cm) from 4 sites in a coastal lagoon in Italy in September 2003, at concns from 43 to 4600 ng/g dry weight(2). Benzo(a)pyrene was detected in sediment samples collected in June 2005 from Ruzin, Velke Kozmalovce and Zemplinska Sirava water reservoirs from the Slovak Republic, at mean (range) concns of 450 (272-680), 473 (294-636) and 34.6 (5-55) ng/g dry sediment, respectively(3). Benzo(a)pyrene was detected in sediment samples collected in February 2005 from lake Stora Frillingen, near the Aspvreten air monitoring station outside of Stockholm, at concns (ng/g) ranging from: 39.8-53.3 (from 0-7.6 cm depth); 66.9-78.5 (from 7.6-10.0 cm); 53.7-21.9 (from 10.0-16.0 cm); 16.4-13.6 (from 16.0-25.0 cm); and 8.0-4.9 (from 25.0-50.0 cm depth)(4). Benzo(a)pyrene was detected in 50% of sediment samples collected in October and November 1997 from the Bohai Sea and Yellow Sea, at mean (range) concns of 31.8 (not detected to 278.5) ng/g dry weight(5). Benzo(a)pyrene was detected in surface sediments collected in July 2005 from the Yellow River in China, with concns of 1,120 and 670 ng/L at the two sites that found max total polycyclic aromatic hydrocarbon levels(6). Surficial sediments collected in April 2002 from 9 stations in Xiamen Harbour and two stations in Yuan Dan Lake, China, detected benzo(a)pyrene at concns of 7.2 to 87.7 ng/g(7).[(1) El Deeb KZ et al; Bull Environ Contam Toxicol 78: 373-9 (2007) (2) Fabbri D et al; Chemosphere 64: 1083-92 (2006) (3) Hiller E et al; Bull Environ Contam Toxicol 83: 444-8 (2009) (4) Elmquist M et al; Environ Sci Technol 41: 6926-32 (2007) (5) Ma M et al; Mar Pollut Bull 42: 132-6 (2001) (6) Xu J et al; Chemosphere 67: 1408-14 (2007) (7) Ou S et al; Chemosphere 56: 107-12 (2004)] **PEER REVIEWED** SOIL: Benzo(a)pyrene was detected in soil samples from an oil refinery in Washington state at concns (depth, inches) of 220 (0 to 6); 62 (12 to 24); < 0.5 (24 to 36); and < 0.5 mg/kg (36 to 54)(1). Benzo(a)pyrene has been detected in soil from various terrestrial habitats of the world at concns ranging from 0.4 to 650,000 ug/kg; the highest concn occurred in soil collected less than 10 m from a soot plant in Germany(2). Benzo(a)pyrene was detected in 57 of 62 soil samples collected from Boston, MA, Springfield, MA, and Providence, RI in July 1992 at concns ranging from 0.040 to 13.00 mg/kg(3). Benzo(a)pyrene's concn was measured in agricultural soil samples collected over a period of 100 years; concns in 1846, 1881, 1914, 1944, 1956, 1966, 1980 and 1986 were 18, 6.7, 12, 23, 73, 28, 120, and 72 ng/g, respectively(4).[(1) Erickson DC et al; ASTM Spec Tech Publ, STP 1075(Waste Test Qual Assur; Third Vol): 257-65 (1992) (2) Edwards NT; J Total Environ Qual 12: 427-41 (1983) (3) Bradley LJ et al; J Soil Contam 3: 349-61 (1994) (4) Jones KC et al; Environ Sci Technol 23: 95-101 (1989)] **PEER REVIEWED** SOIL: Benzo(a)pyrene was detected in soil samples obtained from a former wood impregnation plant and a former tar-oil refinery at concns of 44.0 and 98.3 mg/kg soil, respectively(1). Benzo(a)pyrene was detected in soil surrounding the Urx chemical factory in Czechoslovakia in 1989 and 1990 at concns ranging from 230.1 to 2583.3 ng/g(2). Soil samples collected in the vicinity of a large incineration plant in Italy contained benzo(a)pyrene at concns ranging from 84 to 1075 ng/g, avg concn of 580 ng/g(3). The upper 0 to 5 cm of soil collected adjacent to a major arterial road near Brisbane, Australia contained benzo(a)pyrene at a concn of 363 ng/g, 0.5 m from the curb(4). Soil from Iceland near an airfield contained 785 ppb benzo(a)pyrene; near highway traffic, up to 2,000 ppb benzo(a)pyrene was

detected(5). Benzo(a)pyrene was detected in soil from sites in the USSR: Moscow and vicinity, 7-346 ppb; 3 industrial sites, 350-11,000 ppb(5,6). It was detected in agricultural soil: Czechoslovakia, 8.3 to 42.1 ppb; Italy, 8 to 800 ppb(5). In forest soil from Massachusetts and eastern Connecticut, 40 to 1300 ppb benzo(a)pyrene; near Lake Constance, 1.5 to 2.5 ppb dry weight; W. Germany, south of Darmstadt, 1.5 to 4.0 ppb dry weight(5,6). Benzo(a)pyrene was detected in the organic surface layer of soil and the top 10 cm of mineral soil at 10 forest sites near a blast furnace plant in the Netherlands; average concns, ng/g dry weight, at 0.3, 0.5, 1.2, 1.7, 2.0, 2.5, 2.8, 3.4, 4.5, and 6.6 km away from the blast furnace site, respectively: in the litter, 166, 82.5, 32.7, 48.5, 29.1, 16.7, 7.2, 22.3, 15.0, and 4.3; in the fragmentation, 250, 328, 119, 139, 91.4, 97.6, 53.0, 0, 50.4, and 27.1; in the humus, 405, 322, 257, 186, 130, 140, 45.6, 0, 0, and 59.9; and in the mineral soil, 182, 252, 73.4, 24.0, 7.2, 41.5, 6.8, 0, 2.5, and 15.6(7). Benzo(a)pyrene was detected in soil samples collected in Birmingham, UK and Lahore, Pakistan at concns of 149 and 68.6 and 2.39 ug/kg, respectively(8). Benzo(a)pyrene was detected in soil samples from Civic, 18 and Queanbean, 86 ug/kg dry weight, near Lake Burley Griffin, Australia(9). 20 out of 20 soil samples from sites of the Swiss Soil Monitoring Network were found to contain benzo(a)pyrene at concns ranging from 2 to 18 ug/kg dry weight, with a mean concn of 9.1 ug/kg dry weight(10).[(1) Weissenfels WD et al; Appl Microbiol Biotechnol 36: 689-96 (1992) (2) Holoubek I et al; Toxicol Environ Chem 29: 251-60 (1991) (3) Morselli L et al; Chemosphere 18: 2263-73 (1989) (4) Yang SYN et al; Sci Tot Environ 102: 229-40 (1991) (5) Santodonato J et al; pp. 131-6 in Health and Economic Assessment of Polynuclear Aromatic Hydrocarbons. Lee SD, Grant L, eds., Park Forest South,IL: Pathotox Pub Inc (1981) (6) Verschueren K; Handbook of Environmental Data on Organic Chemicals. 3rd ed., New York, NY: Von Nostrand Reinhold p. 298 (1996) (7) Van Brummelen TC et al; Chemosphere 32: 293-314 (1996) (8) Smith DJT et al; Environ Technol 16: 45-53 (1995) (9) Leeming R; Maher W; Org Geochem 18: 647-55 (1992) (10) Berset JD, Holzer R; Int J Environ Anal Chem 59: 145-65 (1995)] **PEER REVIEWED** SOIL: Benzo(a)pyrene was detected in soils from different ecological zones of Brazil and Chile at mean concns ranging from 0.15 (Savanna, Brazil) to 8.5 ug/kg dry weight (industrial Chile)(1). Soils collected to a depth of 1-5 cm in 2003 from the floors of a burnt (due to forest fire) periurban woodland in Spain detected mean levels of benzo(a)pyrene at 7 to 9 ug/kg; in an unburnt rural woodland, an unburnt distant periurban woodland, and an unburnt nearby periurban woodland (relative to the site of the burnt woodland) detected mean concns of 2, 9, and 39-48 ug/kg, respectively(2). Benzo(a)pyrene was detected in 100% of surface soil samples collected (5-30 cm depth) from the outskirts of Beijing in April 2001, mean (range) concns of 0.055 (0.005-0.270) ug/g dried weight(3). Benzo(a)pyrene was detected in soils from Hangzhou, China at concns from not detected to 33.48, ng/g dry weight, with a mean concn of 17.27 ng/g(4).[(1) Barra R et al; Rev Environ Contam Toxicol 191: 1-22 (2007) (2) Garci-Falcon MS et al; Environ Sci Technol 40: 759-63 (2006) (3) Ma LL et al; Chemosphere 58: 1355-63 (2005) (4) Zhu L et al; Chemosphere 56: 1085-95 (2004)] **PEER REVIEWED** ATMOSPHERIC CONCENTRATIONS: CONCN OF B(A)P IN ATMOSPHERE ... DEPENDS ON GEOGRAPHIC LOCATION, PRESENCE OF NEARBY SOURCES OF POLLUTION SUCH AS TRAFFIC HIGHWAYS OR IN DUST, &amp; ON THE SEASON. ... CONCN WERE GREATER IN URBAN THAN IN NON-URBAN AREAS (UP TO 100 TIMES MORE ...) &amp; GREATER IN WINTER THAN IN SUMMER ... &amp; DURING PERIODS OF INCR SMOKE IN ATMOSPHERE.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,

1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V3 95 (1973)] **PEER REVIEWED** URBAN/SUBURBAN: Mean benzo(a)pyrene concns in the air of Zagreb, Yugoslavia for the winters of 1977 to 1978, 1978 to 1979, 1979 to 1980, 1980 to 1981, and 1981 to 1982 ranged from 0-39, 1-27, 0-37, 0-35, and 4-26 ug/cu m, respectively(1). Mean benzo(a)pyrene concns in urban air samples collected in the UK between 1/91 and 12/92 were, ng/cu m: 1.06, London 1991; 0.56, London 1992; 0.65, Stevenage 1991; 0.63, Stevenage 1992; 1.82, Manchester 1991; 1.20, Manchester 1992; 1.73, Cardiff 1991; and 0.58, Cardiff 1992(2). Benzo(a)pyrene was detected in air samples from South Kensington, UK collected between Oct 1985 and Dec 1987 at mean concns of 0.99, 1.44, and 0.19 ng/cu m for particulates collected between 1985 to 1986, for particulates collected in 1987, and for gas phase benzo(a)pyrene collected in 1987, respectively(3). Airborne particulate samples collected from the Upper Silesia region of Poland, in the winter of 1988-89 and the summer of 1989, were found to contain benzo(a)pyrene (number of times detected, concn range in ng/cu m): winter (8, 8.7 to 42.3) and summer (8, 1.8 to 41.6)(4). Benzo(a)pyrene was detected in air samples collected along Exhibition Road, London between 1/91 and 7/92 at concns ranging from < 0.01 to 7.68 ng/cu m, average concn 1.95 ng/cu m(5). Particulate matter collected from the air of La Plata, Argentina between 1983 and 1984, and 1985 and 1986 contained benzo(a)pyrene at concns ranging from, ng/cu m: 1.45 (June-September 1984); 0.25 (September-December 1984); 0.29 (January-April 1985); 2.27 (April-August 1985); 0.0 (August-December 1985); 0.09 (December 1985-January 1986); and 0.11 (March-June 1986)(6). Benzo(a)pyrene was detected in ambient air samples collected from various areas in Stockholm from June 1980 to Dec 1983 at mean concns ranging from 0.1 to 3.0 ng/cu m(7). Benzo(a)pyrene was detected in the particulate phase of air samples collected from Kosnica, Croatia in Feb and Aug of 1990 at mean concns of 3.93 and 1.6 ng/cu m, respectively(8). Winter and summer average concns for benzo(a)pyrene in Kosnica in the particulate phase were 2.1-5.5 ng/cu m, and 0.7-2.5 ng/cu m, respectively(8). Atmospheric samples collected at locations around Birmingham, UK in the winter and summer contained benzo(a)pyrene at a total concn (particulate) of 0.81 (0.73) and 0.25 (0.23)ng/cu m, respectively; the total concn (particulate) at a rural site in the summer was 0.06 (0.06) ng/cu m(9). Benzo(a)pyrene was detected in air particulate matter from Augusta City, Italy during 10/91 to 7/92 at concns ranging from 1.14 in autumn to 6.75 ng/cu m in summer(10). Benzo(a)pyrene ranged in concn from 0.037 to 0.55 ng/cu m, mean 0.21, in air samples collected in Aug to Sept 1989 from Brazzaville, Congo(11). The mean particulate phase benzo(a)pyrene concn in urban Lahore, Pakistan was 9.32 ng/cu m(12). Air samples collected along a transect from the city of Stockholm to the open coastal area of the Baltic Sea contained benzo(a)pyrene at concns ranging from 0.14 to 0.44 ng/cu m(13). 24-hour samples of airborne particulates collected for one year starting in July 1987 in Thessaloniki, Greece, from one site at the city center, and another in the city industrial zone, detected benzo(a)pyrene at mean concns of 6.4 and 7.1 ng/cu m, respectively(14).[(1) Bozicevic Z et al; Sci Total Environ 66: 127-36 (1987) (2) Halsall CJ et al; Environ Sci Technol 28: 2380-6 (1994) (3) Baek SO et al; Sci Total Environ 111: 169-99 (1992) (4) Bodzek D et al; Atmos Environ 27A: 759-64 (1993) (5) Brown JR et al; Sci Total Environ 177: 73-84 (1996) (6) Catoggio JA et al; Sci Total Environ 79: 43-58 (1989) (7) Colmsjo AL et al; Chemosphere 15: 169-82 (1986) (8) Eskinja I et al; Indian J Anal Chem 63: 251-68 (1996) (9) Smith DJT, Harrison RM; Atmos Environ 30: 2513-25 (1996) (10) Librando V, Fazzino SD; Chemosphere 27: 1649-56 (1993) (11) Ngabe B, Bidleman TF; Environ Pollut 76: 147-56 (1992) (12) Smith DJT et al; Atmos Environ 30: 4031-40 (1996) (13) Broman D et al; Environ Toxicol Chem 9: 429-42 (1990) (14) Viras LG et al;

Environ Toxicol Chem 10: 999-1007 (1991)] **PEER REVIEWED** URBAN/SUBURBAN: Ambient airborne concn of benzo(a)pyrene at suburban sites 11-17 km from city center are approx similar to inside and outside detached residential houses; at all sites, monitored benzo(a)pyrene ranged between 2-4 ng/cu m(1). Atmospheric particles in the metropolitan area of Porta Alegre, Brazil, were analyzed from Nov 2001 to Nov 2002, and detected benzo(a)pyrene at mean (range) concns of 1.090 (0.012-10.99), 0.516 (0.013-4.773) and 0.378 (0.013-1.852) ng/cu m from 8 Distrito de Meteoroligia, CEASA and Charqueadas sites, respectively(2). Benzo(a)pyrene was detected in atmospheric particles in Hangzhou, China at concns from 0.041 to 0.118 ug/cu m, with a mean concn of 0.069 ug/cu m(3). Fine and coarse particulate concentrations of ambient air were measured from February 2004 to January 2005 at the Taichun Harbor sampling site near Taiwan; benzo(a)pyrene was detected at less than 2 ng/cu m(4). The mean particulate phase concn of benzo(a)pyrene detected in air samples, collected from the urban center, a background site, and the adjacent coastal area of Athens, Greece in July 2000, was 0.17, 0.10 and 0.02 ng/cu m, respectively(5). Geometric mean concns of BaP detected in outdoor air collected during winter and summer 2002 in Shizuoka, Japan were 0.347 and 0.280 ng/cu m, respectively(6). Benzo(a)pyrene was detected in air samples collected from urban areas of Brazil at average concns ranging from 0.28 to 2.8 ng/cu m (max in Sao Paulo in the summer)(7). Air samplers deployed at remote, rural and urban locations in 22 European countries found 66% of samples detected BaP at concns above the detection limit of 0.50 ng/sample; the estimated air concn was calculated as < 4 to 250 pg/cu m(8). Benzo(a)pyrene was detected in outdoor air in Shimizu, Japan (an industrial area) in summer 2000, at geometric mean (range) concn of 0.23 (0.057-0.8) and 0.41 (0.16-1.5) ng/cu m, respectively(9).[(1) Butler JD, Crossley P; Sci Total Environ 11 9(1): 53-8 (1979) (2) Dallarosa JB et al; Atmos Environ 39: 1609-25 (2005) (3) Zhu L et al; Chemosphere 56: 1085-95 (2004) (4) Fan GC et al; Chemosphere 64: 1233-42 (2006) (5) Mandalakis M et al; Atmos Environ 36: 4023-35 (2002) (6) Ohura T et al; Environ Sci Technol 39: 5592-9 (2005) (7) Barra R et al; Rev Environ Contam Toxicol 191: 1-22 (2007) (8) Jaward FM et al; Environ Toxicol Chem 23: 1355-64 (2004) (9) Ohura T et al; Environ Sci Technol 38: 77-83 (2004)] **PEER REVIEWED** URBAN/SUBURBAN: Benzo(a)pyrene was detected in ambient air samples taken in Chicago, IL and South Haven, MI between July and August 1991 at mean concns of 3040 and 140 pg/cu m(1). Geometric mean concns of benzo(a)pyrene at four sites in New Jersey during the summer and winter of 1982, respectively, were, ng/cu m: 0.23, 1.64 (Newark); 0.14, 1.01 (Elizabeth); 0.20, 0.87 (Camden); and 0.06, 0.32 (Ringwood)(2). Geometric mean concns of benzo(a)pyrene at four sites in New Jersey during the summer and winter of 1983, respectively, were, ng/cu m: 0.21, 1.06 (Newark); 0.14, 0.69 (Elizabeth); 0.11, 0.94 (Camden); and 0.04, 0.17 (Ringwood)(2). Ambient annual average benzo(a)pyrene concns for fine particles found at west Los Angeles, downtown Los Angeles, Pasadena, Rubidoux, and San Nicolas Island in 1982 were 0.32, 0.42, 0.44, 0.18, and < 0.01 ng/cu m, respectively(3). Average benzo(a)pyrene concns in winter (Nov 1988 to Feb 1989) urban air samples collected in Minneapolis, MN and Salt Lake City, UT were 0.3 ng/cu m; range < 0.2 to 1.7 ng/cu m(4). In summer 2005 and winter 2006, benzo(a)pyrene was detected in 12-hour air samples collected from a highway site in urban Atlanta, at mean, range concns of 0.18, 0.05-0.34 (summer) and 0.58, 0.17-1.80 ng/cu m (winter); it was detected at the Georgia Tech campus at mean, range concns of: 0.04, 0.01-0.17 (summer, 12-hr); 0.07, 0.00-0.23 (summer, 24-hr); 0.16, 0.01-1.01 ng/cu m (winter, 12-hr)(5). Total gas and particulate-phase benzo(a)pyrene was detected in air samples collected from October 1997 to May 2001 in Jersey

City, Camden, New Brunswick, Sandy Hook and Washington Crossing, New Jersey, at mean (range) concns of, respectively, 0.19 (0.012-1.4), 0.14 (0.027-0.90), 0.10 (0-0.37), 0.038 (0-0.23) and 0.077 (0.006-0.63) ng/cu m(6).[(1) Pirrone N et al; Environ Sci Technol 29: 2123-32 (1995) (2) Greenberg A et al; Atmos Environ 19: 1325-39 (1985) (3) Rogge WF et al; Atmos Environ 27A: 1309-30 (1993) (4) Hawthorne SB et al; Environ Sci Technol 26: 2251-62 (1992) (5) Yan B et al; Environ Sci Technol 43: 4287-93 (2009) (6) Gigliotti CL et al; Environ Sci Technol 39: 5550-9 (2005)] **PEER REVIEWED** INDOOR: Indoor air samples collected from homes in communes in Xuan Wei, China which burn smoky coal, smokeless coal, and wood for fuel contained benzo(a)pyrene at concns ranging from 5.1 to 19, 0.12 to 12, and 1.3 to 3.2 ug/cu m, respectively(1). Benzo(a)pyrene was detected in the particulate-phase of indoor air samples from a home with a kerosene heater at concns ranging from 0.24 to 2.0 ng/cu m(2). Benzo(a)pyrene was detected in the indoor air of homes at concns of: 1.6 and 3.3 ng/cu m in the kitchen and living room, respectively, of homes with smokers (with gas heat and electric appliances); and 0.28 and 0.31 ng/cu m, respectively, in the kitchen and living room of homes with non-smokers (with electric heat and electric appliances)(3). It was detected in the air of homes in Columbus, OH at average concns of, ng/cu m: 0.91, for homes with gas utilities; 2.75, for homes with gas utilities and smokers; 0.80, for homes with gas utilities and a fireplace; 1.82, for homes with gas utilities, smokers, and a fireplace; and 0.07, for homes with electrical utilities; the outdoor air concn was 1.38 ng/cu m(4). In February-March 2003, benzo(a)pyrene was detected in the air of homes with and without wood-burning appliances, and at an ambient outdoor site in a Swedish residential neighborhood, at mean (median, range) concns for sum of gaseous and particle phase (ng/cu m) of 0.63 (0.52, 0.09-2.2), 0.16 (0.12, 0.09-0.48), and 0.37 (0.37, 0.17-0.54), respectively; these values exceed the Swedish health-based guideline of 0.1 ng/cu m(5). Geometric mean concns of BaP detected in indoor personal, living room, bedroom, and workplace air collected from 21 households during winter 2002 in Shizuoka, Japan were 0.334, 0.374, 0.395 and 0.316 ng/cu m, respectively; concns detected during summer 2002 were 0.263, 0.264, 0.255, and 0.250 ng/cu m, respectively, and 0.255 ng/cu m from air collected in kitchens(6). Benzo(a)pyrene was detected in indoor air in Shimizu, Japan (an industrial area) in summer 2000 and winter 2001, at geometric mean (range) concns of 0.24 (0.048-1.2) and 0.34 (0.065-0.96) ng/cu m, respectively(7).[(1) Chuang JC et al; Atmos Environ 26A: 2193-201 (1992) (2) Mumford JL et al; Environ Sci Technol 25: 1732-8 (1991) (3) Wilson NK, Chuang JC; Polynucl Aromat Hydrocarbons: Meas, Means, Metab, Int Symp 11th Cooke M et al eds, Battelle Press: Columbus, OH (1991) (4) Mitra S, Wilson NK; Environ Int 18: 477-87 (1992) (5) Gustafson P et al; Environ Sci Technol 42: 5074-80 (2008) (6) Ohura T et al; Environ Sci Technol 39: 5592-9 (2005) (7) Ohura T et al; Environ Sci Technol 38: 77-83 (2004)] **PEER REVIEWED** SOURCE DOMINATED: Benzo(a)pyrene was detected in air samples collected near the Urx chemical factory in Czechoslovakia in 1989 at concns ranging from 11.5 to 41.9 ng/cu m(1). Benzo(a)pyrene was detected in air particulate matter colleted in Bahrain from 7/31/91 to 8/4/91 (during the burning of the oil fields in Kuwait) at concns ranging from 0.42 to 1.12 ng/cu m(2). Particulate phase benzo(a)pyrene was identified during the burning of intense savanna fires carried out at Lamto in the Ivory Coast during January 1991 at concns ranging from 12 to 4.0 picog/cu m; atmospheric background ranged from 0.02 to 0.03 picog/cu m(3). The mean particulate phase benzo(a)pyrene concn in urban Lahore, Pakistan was 7.93 ng/cu m(4). Air particulate matter collected adjacent to a major arterial road near Brisbane, Australia during Sept 1987 contained benzo(a)pyrene at

a mean concn of 0.89 ng/cu m(5). Benzo(a)pyrene was detected in the ambient air, gas phase and particle-bound, of a petrochemical complex in southern Taiwan between 10/93 and 7/94; concns ranged from less than 25 ng/cu m in the gas phase to approx 100 to 175 ug/g associated with particles(6). Ambient air samples collected over a three-month period in the fall of 1982 near a Horizontal Stud Soderberg plant in Jonquiere, Quebec contained benzo(a)pyrene at geometric mean concns of (range), ng/cu m: 26.4 (1 to 170); 48 (2 to 388); and 58 (1 to 545)(7).[(1) Holoubek I et al; Toxicol Environ Chem 29: 251-60 (1991) (2) Madany IM, Raveendran E; Sci Total Environ 116: 281-9 (1992) (3) Masclet P et al; J Atmos Chem 22: 41-54 (1995) (4) Smith DJT et al; Atmos Environ 30: 4031-40 (1996) (5) Yang SYN et al; Sci Tot Environ 102: 229-40 (1991) (6) Tsai JH et al; Environ Intern 21: 47-56 (1995) (7) Roussel R et al; J Air Waste Manag Assoc 42: 1609-13 (1992)] **PEER REVIEWED** RURAL/REMOTE: Benzo(a)pyrene was detected in particulate air samples collected from a remote site of the Mediterranean Sea situated in Corsica, France during March to April 1986 at concns ranging from 0 to 0.06 ng/cu m(1). Benzo(a)pyrene was detected in air samples collected from two rural sites, Folkstone and Ashford, UK, during April to May 1986 at concns ranging from 0.41 to 0.45 ng/cu m(2). Airborne particulate matter collected during 1991-1992 and 1992-1993 from the Antarctic Station Terra Nova Bay contained benzo(a)pyrene at average concns of (picog/cu m) 8.4 and 6.0, ranging from 0.6-41.4 and < 0.4-20.6, respectively(3); samples collected from 1990-1991 detected concns ranging from 0.9-54.6 picog/cu m(4). Winter average concns for benzo(a)pyrene in Zavizan, Croatia in the particulate phase were 0.25-0.45 ng/cu m (0.42 mean concn in February 1990); summer average concns were 0.10 to 0.15 ng/cu m (0.31 mean concn in August 1990)(5). Benzo(a)pyrene was detected in air samples collected at Ellesmere Island in the Arctic during 1992 at mean (max) concns of 1.0 (1.7) picog/cu m from May to Sept and 20.3 (88.8) picog/cu m from Oct to April(6). Atmospheric samples collected on the Greenland Ice Sheet during the winter-spring 1989 and spring-summer 1989 contained benzo(a)pyrene at concns ranging from < 0.1 to 1.8 picog/cu m in the particulate fraction(7). In 2000-2002, BaP was detected in air collected at a background site in Finokalia, east of Greece, at total gas and particulate concns of 0.04 ng/cu m(8).[(1) Masclet P et al; Atmos Environ 22: 639-50 (1988) (2) Baek SO et al; Sci Total Environ 111: 169-99 (1992) (3) Caricchia AM et al; Environ Pollut 87: 345-56 (1995) (4) Chiavarini S et al; Intern J Environ Chem 55: 331-40 (1994) (5) Eskinja I et al; Indian J Anal Chem 63: 251-68 (1996) (6) Fellin PA et al; Environ Toxicol Chem 15: 253-61 (1996) (7) Jaffrezo JL et al; Atmos Environ 27A: 2781-5 (1993) (8) Tsapakis M, Stephanou EG; Environ Sci Technol 39: 6584-90 (2005)] **PEER REVIEWED** RURAL/REMOTE: The average particle-associated concn of benzo(a)pyrene in the atmosphere of the lower Chesapeake Bay Region during 1991 was 0.070, 0.015, and 0.005 ng/cu m for the fall/winter, spring, and summer, respectively(1). Wet and dry deposition fluxes of benzo(a)pyrene to the Chesapeake Bay in 1991 were 1 and 5 ug/sq m yr for the Southern Bay and 2 and 4 ug/sq m yr for the Northern Bay, respectively(2). Annual mean benzo(a)pyrene gas-phase (particulate-phase) concns in Eagle Harbor, MI, Sleeping Bear Dunes, MI, Sturgeon Point, NY, and Point Petre, Ontario were 9.3 (11), 10 (21), 13 (44), and 3.0 (45) pg/cu m, respectively(3). In summer 2005 and winter 2006, BaP was detected in 24-hour air samples collected from a rural site in Yorkville, GA, at mean, range concns of 0.00, 0.00-0.01 (summer), and 0.09, 0.03-0.15 ng/cu m (winter)(4). Total gas and particulate-phase BaP was detected in air samples collected from October 1997 to May 2001 in Tuckerton, Chester, Delaware Bay, Alloway Creek, and Pinelands, New Jersey, at mean (range) concns of, respectively,

0.021 (0.001-0.16), 0.044 (0.008-0.34), 0.015 (0.001-0.086), 0.032 (0.0017-0.12), and 0.031 (0.003-0.26) ng/cu m(5).[(1) Dickhut RM, Gustafson KE; Environ Sci Technol 29: 1518-25 (1995) (2) Dickhut RM, Gustafson KE; Mar Pollut Bull 30: 385-96 (1995) (3) Off RM et al; Atmos Environ 30: 3505-27 (1996) (4) Yan B et al; Environ Sci Technol 43: 4287-93 (2009) (5) Gigliotti CL et al; Environ Sci Technol 39: 5550-9 (2005)] **PEER REVIEWED** FOOD SURVEY VALUES: Benzo(a)pyrene in foodstuff (ppb): fresh vegetables 2.85-24.5; vegetable oils 0.4-1.4; coconut oil 43.7; margarine 0.4-0.5; mayonnaise 0.4; coffee 0.3-1.3; tea 3.9; grain 0.19-4.13; oysters and mussels 1.5-9.0; smoked ham 3.2; smoked fish 0.83; smoked bonito 37; cooked sausage 12.5-18.8; singed meat 35-99. Broiled meat 0.17-0.63; charcoal-broiled steak 8.0; broiled mackerel 0.9; barbecued beef 3.3; barbecued ribs 10.5. /from table/[Searle, C. E. (ed.). Chemical Carcinogens. ACS Monograph 173. Washington, DC: American Chemical Society, 1976., p. 706] **PEER REVIEWED** In fruit ... and cereals B(a)P content depends on their source (closeness to industrial areas or traffic highways). ... following amt of B(a)P were found: salad, 2.8-5.3 ug/kg; spinach, 7.4 ug/kg; tomatoes, 0.2 ug/kg; kale, 12.6-48.1 ug/kg; soya beans, 3.1 ug/kg; apples, 0.1-0.5 ug/kg; other fruits, 2-8 ug/kg.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V3: 101 (1973)] **PEER REVIEWED** In meat or fish the amount of benzo(a)pyrene present depends upon the method of cooking: time of exposure, distance from heat source and whether or not the melted fat is allowed to drip into the heat source; in fruit, vegetables and cereals, content depends on their source (closeness to industrial areas or traffic highways)(1). Benzo(a)pyrene has been detected in, ppb: dried and smoked herring, 1.0; smoked sturgeon, 0.8; smoked chub, 1.3; smoked whitefish, 6.6; Kippered cod, 4.5; smoked and broiled Japanese fish at concns ranging from 9 to 37 ppb in Katsuobushi, 7 ppb in Sababushi, 2 ppb in Urumebushi, and 0.2 to 0.3 ppb in smoked horse mackerel; charcoal-broiled steaks, 5.8; barbecued ribs, 10.5; charcoal-broiled hamburger (21% fat), 2.6; charcoal-broiled pork chops, 7.9; charcoal-broiled chicken, 3.7; charcoal-broiled sirloin steak, 11.1; charcoal-broiled T-bone steak, 50.4; flame-broiled T-bone steak, 4.4; smoked ham, 0.7 to 3.2; barbecued beef, 3.5; hot sausage, 0.4; coffee soots, 530 to 670; liquid smokes, 10; coconut oil, 8 to 10; and halibut liver oil, 20(2). Benzo(a)pyrene was detected in the following fruit and plant products, ppb: spinach, 7.4; salad, 2.8 to 5.3; kale, 12.6 to 48.1; soybean, 3.1; apples, 0.1 to 0.5; tomatoes, 0.2; other fruits, 2 to 8; dried yeast, 1.8 to 40.4; tea, 3.9 to 21.3; whiskey, 0.04; prunes, 0.2 to 1.5; cereals, 0.2 to 4.1; coffee soots, 200 to 400; coffee, 15(2); one of 15 brands of whisky, 0.04; baker's dry yeast, 1.8 to 40.4; and dried prunes, 0.2 to 1.5(1). Benzo(a)pyrene was detected in fermented and dried smoked sausage and cooked bologna produced in Norway at 0.04 to 0.15 and 0.04 to 0.08 ppb(2). Benzo(a)pyrene was detected in the following smoked and charcoal-broiled food products, ppb: bologna, 2.0; smoked frankfurters, 2.0; salami, 2.0; various sausages, 1.0; ham, 2.0; Wesphalian ham, 2.0; bacon, 0.5; smoked pork, 0.2 to 0.3; smoked herring, 15.0; various smoked fish, 0.5; Gouda cheese, 0.5; canned smoked oysters, 2.0; charcoal-broiled porterhouse steak, 3.0; hamburger, 20.0; charcoal-broiled frankfurter, 5.0; charcoal-broiled Chinese sausages, 25.0(2).[(1) IARC; Certain Polycyclic Aromatic Hydrocarbons and

Heterocyclic Compounds 3: 91-136 (1973) (2) Lo M, Sandi E; Res Rev 69: 35-86 (1978)] **PEER REVIEWED** Benzo(a)pyrene was detected in, ug/kg: 38 samples of margarine at a mean concn of 0.5, range < 0.06 to 5.8; 10 mussel samples, mean concn 18, range 6.8 to 38; 5 spinach samples grown within 0.5 km of the runway of an international airport, mean 0.3, range 0.1 to 0.5; and kale grown within 0.5 km of the runway of an international airport, mean 4.6, range 1.9 to 12(1). Benzo(a)pyrene was detected in the following cereal products available in Finland, average concn, ug/kg: bolted wheat flour, 0.4; rolled oats, 0.3; milled oats, 0.4; milled wheat, 0.2; bran, 5.4; and smoked oats, barley and beans 0.6 to 160(2). Benzo(a)pyrene was detected in the following South Indian foods, ug/g: pyrolyzed Chappatti, 0.676; pyrolyzed bread toast, 0.226; pyrolyzed cutlet, 1.418; pyrolyzed calamus, 0.008; oil-fried, salted and sun-dried chiles, 1.995; Sundakkai, 0.060; oil-fried, salted and sun-dried whitebait fish, 5.730; oil-fried, salted and sun-dried ribbon fish, 60.170; oil-fried, salted and sun-dried seer fish, 10.290; and sun-dried ribbon fish, 0.105(3). Samples of fish and shrimp purchased from local fish markets in Kuwait during May 1993 were found to contain benzo(a)pyrene at an average concn of 1.18 ug/kg dry weight(4). Benzo(a)pyrene has been detected in the following smoked foods, ppb: ham, 0.7; kippered cod, 4.0; smoked whiting, 6.6; barbecued beef, 3.3; and hot sausage, 0.4(5). Benzo(a)pyrene was detected in the following foods obtained from supermarkets in Milan, Italy, ug/kg: cauliflower, 0.006; beet greens, 0.096; squash, 0.452; lettuce, 0.007; tomatoes, 0.003; potatoes, 0.001; apples, 0.527; peeled apples, 0.063; citrus fruits, 0.030; bread, 0.017; pasta, 0.017; rice, corn, 0.022; trout, 0.027; cod, 0.14; dried cod, 0.026; milk and yogurt, 0.336; cheese, 0.014; beef, 0.613; pork, 0.035; rabbit, 0.015; chicken, 0.015; beef liver, 0.032; cured meats, 0.034; eggs, 0.015; barbecued beef, 1.445; barbecued pork, 0.121; olive oil, 0.102; butter, 0.016; chocolate, 0.332; wine, 0.009; beer, 0.029; coffee, 0.011; and pizza baked in a wood-burning oven, 0.025(6). 20 out of 34 samples of shell-free fresh-frozen and precooked-frozen mussels, Perna canaliculus, bought from markets throughout the island of Tenerife, Canary Islands, between Sept 1992 and May 1993 were found to contain benzo(a)pyrene at concns ranging from 13 to 190 ng/g dry weight(7).[(1) Vaessen HAMG et al; Toxicol Environ Chem 16: 281-94 (1988) (2) Tuominen JP et al; J Agric Food Chem 36: 118-20 (1988) (3) Sivaswamy SN et al; Bull Environ Contam Toxicol 47: 251-60 (1991) (4) Saeed T et al; Environ Int 21: 255-63 (1995) (5) Malanoski AJ et al; J Assoc Off Anal Chem 51: 114-21 (1968) (6) Lodovici M et al; Food Addit Contam 12: 703-13 (1995) (7) Hernandez JE et al; Bull Environ Contam Toxicol 55: 461-8 (1995)] **PEER REVIEWED** Benzo(a)pyrene was detected in native German vegetable oils at the following median concns, ug/kg: olive oils, 0.7; safflower oils, 0.3; sunflower oils, 0.7; maize germ oils, 1.3; linseed oil, 0.9; and wheat germ oil, 1.3(1). Benzo(a)pyrene was detected in, ug/kg wet weight: fresh oysters, 0.4 to 1.0; canned oysters, 0.2; canned smoked oysters in oil, 10.1 to 12.2; oil from canned smoked oysters, 75.8; canned sea mussels, 1.5 to 1.7; canned blue mussels, 0.3; and canned mussels, 0.8(1). Benzo(a)pyrene levels in seafood from retail outlets and fast food chains in the Toronto metropolitan were, ug/kg: 0.06 to 4.6, lobster paste; 2.6 lobster meat; 0.76, smoked mussels; 1.4, mussels in brine; smoked oysters, 2.3 to 13.3; unsmoked oysters, 0.79; frozen shrimp, not detected to 0.03; and canned shrimp, 0.18 to 3.8(2). Benzo(a)pyrene levels in cereals from retail outlets and fast food chains in the Toronto metropolitan were, ug/kg: not detected to 0.11, bran cereals; 0.03, corn puffed cereal; and 0.04 corn puffed cereal(2). Infant formula and coffee whitener from retail outlets in the Toronto metropolitan area contained 0.04 to 1.2 and 0.12

ug/kg benzo(a)pyrene, respectively(2). Benzo(a)pyrene was detected in Edam cheese and Cheddar cheese at 0.3 and 0.5 ppb, respectively(3). In The Total Human Environmental Exposure Survey conducted in 1987 to 1988, the concn of benzo(a)pyrene in 58 prepared meals ranged from 0.005 to 1.17 ug/kg, avg 0.15 ug/kg(4).[(1) Speer K et al; J High Resol Chromatogr 13: 104-11 (1990) (2) Lawrence JF, Das BS; Int J Environ Anal Chem 24: 113-31 (1986) (3) Joe FLJR et al; J Assoc Off Anal Chem 67: 1076-82 (1984) (4) Menzie CA et al; Environ Sci Technol 26(7): 1278-84 (1992)] **PEER REVIEWED** PLANT CONCENTRATIONS: Olives picked from various locations in the Valley of Florence, Italy, in a radius of about 15 km from Florence, contained benzo(a)pyrene(1). Benzo(a)pyrene was detected in samples of mosses, Hypnum cupressiforme, and needles taken from Pinus silvestris in the vicinity of a chemical factory that processes crude tar and benzene in Czechoslovakia in Sept 1989; concns ranged from 138.1 to 2976.2 ng/g and 27.2 to 519.1 ng/g, respectively(2). Benzo(a)pyrene was detected in aquatic moss samples collected from the Danube and Traun rivers in Austria at concns ranging from 13-28 and 3.4-4.7 ug/kg dry weight, respectively(3). Benzo(a)pyrene was detected in leaves of the bay evergreen tree, Laurus nobilis, taken from 15 different sites in the Valley of Florence, Italy in 1990; concns in the winter ranged from 2.5 to 22.5 ug/kg dry weight(4). Benzo(a)pyrene was detected in pine needle samples collected throughout the UK in 1994 at concns ranging from 0.49 to 7.9 ng/g dry weight(5). Natural benzo(a)pyrene background levels, ppb dry wt: chrysanthemum, 1.20; post oak leaves, 30; and little bluestem leaves, 30(6). Mean bark mass concn of benzo(a)pyrene detected in 15 species of tree bark collected in August 2003 from the main campus of Xiamen University, China, was 2.21 ng/g dry bark; mean lipid mass concn was 28.0 ng/g lipid(7).[(1) Ignesti G et al; Bull Environ Contam Toxicol 48: 809-14 (1992) (2) Holoubek I et al; Toxicol Environ Chem 29: 251-60 (1991) (3) Chovanec A et al; Chemosphere 29: 2117-33 (1994) (4) Lodovici M et al; Sci Total Environ 153: 61-8 (1994) (5) Tremolada P et al; Environ Sci Technol 30: 3570-7 (1996) (6) Sims RC, Overcash MR; Res Rev 88: 1-68 (1983) (7) Zhao Y et al; Environ Sci Technol 40: 5853-9 (2006)] **PEER REVIEWED** FISH/SEAFOOD CONCENTRATIONS: Benzo(a)pyrene concns in the digestive glands of lobsters captured at various sites in and around Sydney Harbor, Nova Scotia in May 1982 ranged from 0.1 to 1430 ng/g dry weight; the concn in digestive glands and tails following 3 months exposure to creosoted timbers and transfer to clean water for 13 days ranged from 100 to 860 ng/g wet weight in the digestive gland and 4 to 32 ng/g wet weight in the tail(1). Asian clams, Potamocorbula amurensis, collected from Suisun Bay, CA contained benzo(a)pyrene at concns ranging from 35 to 60 ng/g dry weight(2). Benzo(a)pyrene was detected in oysters collected from the island of Ko Sichang, green mussels from a mussel farm at Ang Hin, and scallops from trawls (upper Gulf of Thailand) at concns of 3.5, 1.0, and 8.1 ng/g(3). Concentrations of benzo(a)pyrene in mussels collected from various sites in Port Phillip Bay, Australia in May and August 1986 ranged from 0.43 to 0.96 ug/kg dry weight in water with no direct source of hydrocarbons, 1.3 to 2.3 ug/kg dry weight in areas where the main sources of hydrocarbons is urban drainage, and 6.5 to 29 ug/kg dry weight in sites close to the discharge of a major oil refinery(4). Benzo(a)pyrene was detected in clams collected from a number of sites in the Great Barrier Reef Region, Australia at concns ranging from < 0.004 to 0.01 ug/kg wet weight(5). Benzo(a)pyrene was detected in shellfish and fish collected from the Gulf of Naples between March and Dec 1988 at the following concns, ug/kg wet weight: 5, common mussel; 21, edible cockle; 5, razor fish; and 6,

shortnecked clam; 86, anchovy; 12, bogue; 8, brill; 44, cleaver wrasse; 13, comber; 3, horse mackerel; 3, pandora; 7, rainbow wrasse; 7, scorpion fish; and 21, spotted weever(6). Benzo(a)pyrene was detected in oysters collected from five sites in Mermaid Sound and one site outside the Sound on 9/15/82 at concns ranging from < 0.01 to 5 ug/kg wet weight(7).[(1) Uthe JF, Musial CJ; Bull Environ Contam Toxicol 37: 730-8 (1986) (2) Pereira WE et al; Mar Pollut Bull 24: 103-9 (1992) (3) Hungspreugs M et al; Mar Pollut Bull 15: 213-8 (1984) (4) Murray AP et al; Mar Pollut Bull 22: 595-603 (1991) (5) Bagg J, Smith JD; ACS Natl Meet 28: 328-30 (1988) (6) Cocchieri RA et al; Mar Pollut Bull 21: 15-8 (1990) (7) Kagi R et al; Int J Environ Anal Chem 22: 135-53 (1985)] **PEER REVIEWED** Benzo(a)pyrene was detected in the stomach contents of white croaker from various areas in Los Angeles, ng/g dry weight: 330, Queensway Bay; 2900, Cerritos Channel; 310, Reservation Point; < 26, White Point; and 64, Hyperion(1). Benzo(a)pyrene was detected in composites of stomach organisms from juvenile chinook salmon captured from the Duwamish Waterway, WA in 6/86 and the Nisqually River, WA in 6/87 at average concns of 0.57 and < 0.07 ug/g dry weight, respectively(2). Corbicula samples collected from the San Joaquin River and its tributaries in 1992 contained benzo(a)pyrene at the following concns, ng/g: 1.1, Orestimba Creek; 1.5, Dry Creek; < 0.5, Mokelumne River; and 1.4, Stanislaus River(3). Average benzo(a)pyrene concns in benthic macroinvertebrates, crayfish, redbreast sunfish, and central stonerollers collected from East Fork Poplar Creek in Oak Ridge, TN were 1.63, 10.00, 0.35, and 11.70 ug/kg, respectively(4). Benzo(a)pyrene was detected in fish samples from the Black River and the Potomac River at 7 and 1 ppb, respectively(5). Benzo(a)pyrene was detected in tissue samples, in ppb, from: codfish (not detected-1.5); crab (not detected-3); mollusk (2.4 to 60, max in Greenland); oyster (0.1-7.0); clam (not detected-0.3); menhaden (1.5); shrimp (not detected in TX); and Lake trout ( < 1 ppb)(6,7). Mussels from Saudafjord, Norway, in 1976 detected concns of benzo(a)pyrene from 0.517 to 20.8 ppm dry wt(8). Miyagi Prefecture, Japan, mussels contained 0.40 to 2.64 ppb; oysters, 0.78 ppb; corb-shell, 0.21 ppb; and shortnecked crab, 0.41 to 1.79 ppb(9).[(1) Malins DC et al; Environ Sci Technol 21: 765-70 (1987) (2) McCain BB et al; Arch Environ Contam Toxicol 19: 10-6 (1990) (3) Pereira WE et al; Environ Toxicol Chem 15: 172-80 (1996) (4) Rao VR et al; Ecotoxicol Environ Safety 33: 44-54 (1996) (5) Vassilaros DL et al; Anal Chem 54: 106-12 (1982) (6) Verschueren K; Handbook of Environmental Data on Organic Chemicals. 4th ed., New York, NY: John Wiley and Sons, p 304 (2001) (7) Fazio T, Howard JW; pp.461-506 in Handbook of Aromatic Hydrocarbons; Bjorseth A, ed (1983) (8) Bjorseth A et al; Sci Total Environ 13: 71-86 (1979) (9) Takatsuki K et al; JAOAC 68: 945-49 (1985)] **PEER REVIEWED** Benzo(a)pyrene was detected in muscle tissues of bottom dwelling fish (Solea solea), bivalve (Donax truaulus), crustacean shrimp (Peneaus japonicus), and fish (Diplodus vulgaris) from Abu Qir bay, Egypt, during winter 2004 at concns of 358.06, 30.33, 70.67 and 32.50 ng/g wet weight, respectively(1). Benzo(a)pyrene was detected in tissue of mussel (Mytilus galloprovincialis) from a remote area in the Adriatic sea collected in September 2003, at mean concn of < 5 ng/g dry weight; there was no change in concn after transplant to 3 different sites in a coastal lagoon in Italy, after 30 days exposure(2).[(1) El Deeb KZ et al; Bull Environ Contam Toxicol 78: 373-9 (2007) (2) Fabbri D et al; Chemosphere 64: 1083-92 (2006)] **PEER REVIEWED** ANIMAL CONCENTRATIONS: Benzo(a)pyrene was detected in two populations of sea lions, one from Mar del Plata and the second from Punta Bermeja, Argentina in the fur at 2.970 and 0.230 ng/g fresh weight, respectively; in the blood at average concns

of 6.030 and 3.750 ng/g dry weight, respectively; and in the liver at average concns of 4.12 and 1.270 ng/g fresh weight, respectively(1).[(1) Marsili L et al; Chemosphere 34: 759-70 (1997)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/9569942?dopt=Abstract" target=new>PubMed Abstract MILK CONCENTRATIONS: ENVIRONMENTAL: Benzo(a)pyrene concns of 7.6 to 387 ng/mL (with a mean value of 129.5 ng/mL) were found in samples of milk from ten nursing mothers.[Health and Welfare Canada; Polycyclic Aromatic Hydrocarbons p.38 (1979) Report No. 80-EHD-50] **PEER REVIEWED** ENVIRONMENTAL: Benzo(a)pyrene was detected in 51 samples of Dutch milk at concns ranging from 0.03 to 0.66 ppb, avg 0.03 ppb(1). Benzo(a)pyrene was detected in dried milk from Canada: skim, 0.1 ppb, infant formula, 1.2 ppb(2). It was identified in milk from the UK in 1979 at 0.005 to 0.02 ppb, avg 0.01 ppb(3).[(1) Betlem JP; Food Inspection Service Amsterdam, Report No. 15, Amsterdam, The Netherlands (1981) (2) Lawrence JF, Weber DF; J Agric Food Chem 32: 794-7 (1984) (3) Dennis MJ et al; Food Chem Toxicol 21: 569-74 (1983)] **PEER REVIEWED** OTHER ENVIRONMENTAL CONCENTRATIONS: In emissions from typical European gasoline engine: 1.9-26 ug/L fuel burnt; In exhaust condensate of gasoline engine: 0.05-0.08 mg/L gasoline consumed; In cigarette smoke: 2.5 ug per 100 cigarettes; In emissions from open burning of scrap rubber tires: 85-114 mg/kg of tire; In emissions from combustion of fuel oil: 0.13 mg/ton (large furnaces > 1,000 hp), 10 mg/ton fuel (small furnaces < 1,000 hp).[Verschueren, K. Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. John Wiley &amp; Sons. New York, NY. 2001, p. 296] **PEER REVIEWED** In gasoline: 0.13 mg/L to 8.28 mg/kg; In fresh motor oil: 0.02-0.10 mg/kg; In used motor oil: 5.8 mg/L; In used motor oil after 5,000 km: 83-162.0 mg/kg; In used motor-oil after 10,000 km: 110-242 mg/kg; In crude oils: 2.8 ppm (Kuwait), 0.75 ppm (South Louisiana), 1.3 mg/L (Lybia), 1.6 mg/L (Venezuela), 0.4 mg/L (Persian Gulf); In diesel oil (gasoil): 0.026 mg/L; In asphalt up to 0.0027 wt %; In coal tar pitch up to 1.2 wt %; Constituent of coal tar creosote: 1 wt %; In coal tar: 9.7 g/kg; In carbon black: 250 mg/kg; In compost: 4,410 ug/kg dry weight; In horse manure: 44 ug/kg dry weight.[Verschueren, K. Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. John Wiley &amp; Sons. New York, NY. 2001, p. 295] **PEER REVIEWED** Soot from the burning of oil fuel, a mixture of oil and solid fuel, and solid fuel contained benzo(a)pyrene at 10.50, 109.10, and 51.25 mg/kg, respectively(1). Benzo(a)pyrene was detected in crude oil from S. Louisiana, Kuwait, and Qatar at 0.75, 2.8 , and 3.6 mg/kg, respectively(2). It was detected in No. 2 Fuel oil, diesel fuel, No. 2 heating oil, and No. 2 diesel fuel oil at 0.6, 0.07, 0.03, 0.13 mg/kg, respectively(2). Benzo(a)pyrene was detected in residual petroleum products: Bunker C No. 6 oil, 44 mg/L; asphalt, not detected to 27 mg/kg; and paving asphalts, 1.3 mg/kg(2). It was detected in new engine oil, 0.03 mg/kg, lube oil, 0.23 mg/kg, and used engine oil (crankcase oils), 0.6 to 217 mg/kg(2). Benzo(a)pyrene was detected in bituminous coal at concns ranging from 6 to 20 ppm(3). Typical benzo(a)pyrene concns in gaseous and particulate emissions from the burning of different fuels are, mg/kg fuel burned: coal, power plant, 4X10-5 to 0.002; oil, power plant, 7X10-7 to 1.5X10-5; refuse, municipal incinerator, 4X10-5; gasoline, noncatalytic automobile, 0.016; gasoline, catalytic automobile, 4X10-4; coal, residential stove, 25; wood, residential stove, 0.05 to 6.5; charcoal,

residential stove, 3.3X10-4; wood, residential hot water boiler, 0.02; peat, residential hot water boiler, 0.06; wood, residential fireplace, 0.005 to 1.9; and brush, open slash burning 2 to 12(3). Benzo(a)pyrene was detected in oil collected from four Kuwait oil lakes in Sept 1992, concn tended to increase with weathering time: initial concns ranged from 0.46 to 5.3 mg/kg, after 21 months concns ranged from 0.64 to 22.2 mg/kg(4). Benzo(a)pyrene was detected in surface road dusts collected in various locations throughout Birmingham, UK and Lahore, Pakistan at concns ranging from 0.71 to 2000 ug/kg(5).[(1) Knecht U et al; Br J Ind Med 46: 479-82 (1989) (2) American Petroleum Institue; Washington,DC: Amer Petrol Instit API Publ No 4593, Order No 841-45930 (1994) (3) Anderson JW et al; Sources, Fates and Effects of Aromatic Hydrocarbons in the Alaskan Marine Environment with Recommendations for Monitoring Strategies NTIS PB86-168-291/AS Washington, DC: USEPA (1986) (4) Saeed T et al; Arch Environ Contam Toxicol 29: 45-51 (1995) (5) Smith DJT et al; Environ Technol 16: 45-53 (1995)] **PEER REVIEWED** Benzo(a)pyrene was detected in 29 archived anaerobically digested, lagoon dried sewage sludges applied at the Woburn Market Garden, UK between 1942 and 1961 at concns ranging from 0.1 to 7.5 mg/kg(1). Creosote/chlorphenols-treated wood utility poles and railway ties were found to contain benzo(a)pyrene at a concn of 1,116 and 461 mg/kg wet weight, respectively(2). Concns of benzo(a)pyrene associated with particulates emitted from a spark-ignited engine and a diesel engine were 109 and 3 ug/g particulates, respectively(3). The mean concn of benzo(a)pyrene in used lubricating oils from gasoline, M15, diesel and gas fueled vehicles was 22, 31, 0.8, and 13 ppm, respectively(4). Benzo(a)pyrene was identified in crankcase oil, fire soot and car soot at mean concns of 1.89, 1.37, and 1.99 ug/g(5). Benzo(a)pyrene was detected in coal tar and carbon black at concns of 9.7 mg/g, and 250 ug/g, respectively(6). Benzo(a)pyrene was identified as a particulate organic emitted during the open burning of scrap rubber tires(7). Benzo(a)pyrene was detected in airborne particulate matter from the burning of wood and other vegetation (concentration in ug/g): Australian native wood (27.3); Australian native plants (26.2); cooking meat using Australian native plants as fuel (37.2); large-scale backyard burn of native Australian and introduced species and cardboard products (70.5); large-scale bush fire (194); leaves from Australian native vegetation (6.0); wood from Australian native vegetation (5.5); commercial incinerator burning paper and cardboard products (2.2); cigarette mainstream and sidestream smoke (21.0); cigarette sidestream smoke (50.8)(8).[(1) Wild SR et al; Chemosphere 20: 703-16 (1990) (2) Wan MT; J Environ Qual 23: 1297-1304 (1994) (3) Van Donkelaar P; Sci Total Environ 92: 165-79 (1990) (4) Ostman CE et al; Polynucl Aromat Hydro: Chem Charact Carcin 9th: 729-44 (1986) (5) O'Malley VP et al; Environ Sci Technol 30: 634-9 (1996) (6) Nishioka M et al; Environ Sci Technol 20: 1023-7 (1986) (7) DeMarini DM et al; Environ Sci Technol 28: 136-41 (1994) (8) Freeman DJ, Cattell FCR; Environ Sci Technol 24: 1581-5 (1990)] **PEER REVIEWED** Average benzo(a)pyrene emission factors for the burning of almond, walnut, fir and pine were 28, 6, 35, and 19 ug/kg, respectively(1). Average benzo(a)pyrene concns in the emissions of coke ovens, diesel engines, highway tunnels, gasoline engines, and wood combustion in the Chicago metropolitan during 1990 to 1992 were 0.00533, 0.302, 0.0626, 0.0270, and 0.203 ug/cu m, respectively(2). Ashes from the electrostatic precipitator, which removes fume particulate, of a large incineration plant in Italy contained benzo(a)pyrene at a concn of 5490 ng/g(3). Benzo(a)pyrene was detected in pig and cattle manure slurry taken from pits on farms located at Swiss Soil Monitoring Network sites at mean concns of 5.5 and 6.5 ug/kg dry weight, respectively(4). Samples of compost from 3 different compost

piles in Switzerland were found to contain benzo(a)pyrene at concns ranging from 33 to 358 ug/kg dry weight, mean concn 220.0 ug/kg dry weight(4). Benzo(a)pyrene was detected in sewage sludges containing varying amounts of industrial waste waters at concns ranging from 98 to 921 ug/kg dry weight(4). Sludge samples from 12 UK sewage treatment plants contained benzo(a)pyrene at concns of 16 to 400 ppb dry wt and 0.35 to 11.43 ppm dry wt(5). Benzo(a)pyrene was detected in smoke particles from open burn smoke of new plastic grocery bags, roadside litter, and landfill trash in Chile at concns of 105.4, 116.3 and 64.1 ng/mg; it was not detected in new plastic bags from the US(6). Smoke particulate in 9 brands of cigarettes from leading domestic US tobacco companies were analyzed using a smoke machine under ISO conditions (35 mL puff volume, 60 second puff interval), and detected benzo(a)pyrene in all samples at concns from 10.0 to 15.8 ng/cigarette(7). Levels of benzo(a)pyrene in full, light, and ultra-flavored cigarettes under ISO conditions ranged from 12.3-18.5, 8.2-11.6, and 6.0-8.3 ng/cigarette, respectively; under Health Canada conditions (55 mL puff volume, 30 second puff interval, 100% vent holes block), full, light, and ultra-flavored cigarettes had BaP concn levels of 21.8-27.5, 14.9-23.7, and 14.6-17.4 ng/cigarette, respectively(7). Benzo(a)pyrene was detected in the extracts of settled house dust collected in vacuum cleaners from homes in Ottawa, Ontario, at mean, median and range concns of 2.91, 0.803, and 0.040-38.8 ug/g, respectively(8).[(1) Jenkins BM et al; Environ Sci Technol 30: 2462-2469 (1996) (2) Khalili NR et al; Atmos Environ 29: 533-42 (1995) (3) Morselli L et al; Chemosphere 18: 2263-73 (1989) (4) Berset JD, Holzer R; Int J Environ Anal Chem 59: 145-65 (1995) (5) McIntyre AE et al; Anal Letters 14: 291-309 (1981) (6) Simoneit BRT et al; Environ Sci Technol 39: 6961-70 (2005) (7) Ding YS et al; J Agric Food Chem 55: 5966-73 (2007) (8) Maertens RM et al; Environ Sci Technol 42: 1747-53 (2008)] **PEER REVIEWED** ENVIRONMENTAL STANDARDS & REGULATIONS: CERCLA REPORTABLE QUANTITIES: Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 1 lb or 0.454 kg. The toll free number of the NRC is (800) 424-8802. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV.D.3.b).[40 CFR 302.4 (USEPA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of August 19, 2009: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED** RCRA REQUIREMENTS: U022; As stipulated in 40 CFR 261.33, when benzo(a)pyrene, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5).[40 CFR 261.33 (USEPA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of August 19, 2009: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED**

CLEAN WATER ACT REQUIREMENTS: For the maximum protection of human health from the potential carcinogenic effects due to exposure of polynuclear aromatic hydrocarbons through ingestion of contaminated water and contaminated aquatic organisms, ... therefore, the levels which may result in incremental increase of cancer risk over the lifetime are estimated at 1x10-5, 1x10-6, and 1x10-7. The corresponding criteria /for ambient water/ are 28.0 ng/l, 2.8 ng/l, and 0.28 ng/l, rspectively. If the above estimates are made for consumption of aquatic organisms only, excluding consumption of water, the levels are 344.0 ng/l, a 31.1 ng/l, and 3.11 ng/l respectively. /Polynuclear aromatic hydrocarbons based on benzo(a)pyrene as the model PAH/[USEPA; Ambient Water Quality Criteria Doc: Polynuclear Aromatic Hydrocarbons p.C-121 (1980)] **QC REVIEWED** The attempt to develop a drinking water criterion for polynuclear aromatic hydrocarbons (PAH) as a class is hindered by several gaps in the scientific data base: (1) The PAH class is composed of numerous compounds having diverse biological effects and varying carcinogenic potential. A "representative" PAH mixture, has not been defined. (2) The common practice of using data derived from studies with benzo(a)pyrene to make generalizations concerning the effects of environmental PAH may not be scientifically sound. (3) No chronic animal toxicity studies involving oral exposure to PAH mixtures exist. (4) No direct human data concerning the effects of exposure to defined PAH mixtures exist. /Polynuclear aromatic hydrocarbons/[USEPA; Ambient Water Quality Criteria Doc: Polynuclear Aromatic Hydrocarbons (Draft) p.C-118 (1980)] **QC REVIEWED** Toxic pollutant designated pursuant to section 307(a)(1) of the Federal Water Pollution Control Act and is subject to effluent limitations. /Polynuclear aromatic hydrocarbons/[40 CFR 401.15 (USEPA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of August 19, 2009: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED** FEDERAL DRINKING WATER STANDARDS: EPA 0.2 ug/L[USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93) To Present] **PEER REVIEWED** Maximum contaminant levels for organic contaminants. ... The following maximum contaminant level for synthetic organic contaminants apply to community water systems and non-transient, non-community water systems: CAS No.: 50-32-8; Contaminant: Benzo[a]pyrene; MCL: 0.0002 mg/L.[40 CFR 141.61 (USEPA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of August 19, 2009: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED** FEDERAL DRINKING WATER GUIDELINES: Maximum contaminant level goals for organic contaminants. (a) MCLGs are zero for the following contaminants: benzo(a)pyrene.[40 CFR 141.50(a) (USEPA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of May 20, 2010: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED** STATE DRINKING WATER GUIDELINES: (AZ) ARIZONA 0.003 ug/L[USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93) To Present] **PEER REVIEWED**

(NH) NEW HAMPSHIRE 0.20 ug/L[USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93) To Present] **PEER REVIEWED** (ME) MAINE 0.05[USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93) To Present] **QC REVIEWED** CHEMICAL/PHYSICAL PROPERTIES: MOLECULAR FORMULA: C20-H12 **PEER REVIEWED** MOLECULAR WEIGHT: 252.31[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 183] **PEER REVIEWED** COLOR/FORM: PALE YELLOW MONOCLINIC NEEDLES FROM BENZENE &amp; METHANOL[Weast, R.C. (ed.). Handbook of Chemistry and Physics. 60th ed. Boca Raton, Florida: CRC Press Inc., 1979., p. C-203] **PEER REVIEWED** Yellowish plates, needles from benzene + methanol; crystals may be monoclinic or orthorhombic.[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 183] **PEER REVIEWED** Yellowish plates (from benzene and ligroin)[Weast, R.C. (ed.) Handbook of Chemistry and Physics. 67th ed. Boca Raton, FL: CRC Press, Inc., 1986-87., p. C-141] **PEER REVIEWED** ODOR: Faint aromatic odor[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 1] **PEER REVIEWED** BOILING POINT: 310-312 deg C at 10 mm Hg[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 183] **PEER REVIEWED** MELTING POINT: 179 deg C[Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley &amp; Sons, Inc. New York, NY 2007., p. 138] **PEER REVIEWED** DENSITY/SPECIFIC GRAVITY: 1.351[Warshawsky D; Patty's Toxicology. (2007). NY, NY: John Wiley &amp; Sons, Inc. Polycyclic and Heterocyclic Aromatic Hydrocarbons. On-line posting date: December 4, 2000.] **PEER REVIEWED** OCTANOL/WATER PARTITION COEFFICIENT: log Kow = 6.13[Demaagd PGJ et al; Environ Toxicol Chem 17: 251-7 (1998)] **PEER REVIEWED**

SOLUBILITIES: Sol in benzene, toluene, xylene, and ether; slightly sol in alcohol[Warshawsky D; Patty's Toxicology. (2007). NY, NY: John Wiley &amp; Sons, Inc. Polycyclic and Heterocyclic Aromatic Hydrocarbons. On-line posting date: December 4, 2000.] **PEER REVIEWED** Very soluble in chloroform[Lide, D.R. CRC Handbook of Chemistry and Physics 88TH Edition 2007-2008. CRC Press, Taylor &amp; Francis, Boca Raton, FL 2007, p. 3-40] **PEER REVIEWED** Solubility in aqueous caffeine is higher than in water; also, native DNA has a solubilizing effect[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V3 92 (1973)] **PEER REVIEWED** In water, 1.62X10-3 mg/L at 25 deg C[May WE et al; J Chem Ref Data 28: 197-200 (1983)] **PEER REVIEWED** SPECTRAL PROPERTIES: MAX ABSORPTION (ALCOHOL): 255 NM (LOG E= 4.44), 265.5 NM (LOG E= 4.66), 274 NM (LOG E= 4.50), 284 NM (LOG E= 4.66), 296.5 NM (LOG E= 4.76), 347 NM (LOG E= 4.10), 364 NM (LOG E= 4.36), 384.5 NM (LOG E= 4.44), 403 NM (LOG E= 3.60)[Weast, R.C. (ed.). Handbook of Chemistry and Physics. 60th ed. Boca Raton, Florida: CRC Press Inc., 1979., p. C-203] **PEER REVIEWED** Absorption maxima (nm) (molar extraction): Solvent: ethanol: 384 (29040), 364 (24069), 346.5 (13195), 403 (3981), 384.5 (27542), 363.5 (22908), 347 (12589), 330 (5754), 296.5 (57544), 284.5 (45709), 274 (31623), 265.5 (45709), 254 (39811), 225 (27542).[Castegnaro, M., G. Grimmer, O. Hutzinger, W. Karcher, H. Kunte, M. LaFontaine, E.B. Sansone, G. Telling, and S.P. Tucker (eds.). Laboratory Decontamination and Destruction of Carcinogens in Laboratory Wastes: Some Polycyclic Aromatic Hydrocarbons. IARC Publications No. 49. Lyon, France: International Agency for Research on Cancer, 1983., p. 45] **PEER REVIEWED** Absorption maxima (nm) (molar extraction): Solvent: pentane: 401 (4200), 391 (4100), 382 (30500), 379 (27200), 377 (27600), 362 (25800), 345 (13200), 330 (5400), 313 (3600), 296 (60800), 283 (44400), 271 (28800), 265 (47200), 254 (39200), 226 (28000).[Castegnaro, M., G. Grimmer, O. Hutzinger, W. Karcher, H. Kunte, M. LaFontaine, E.B. Sansone, G. Telling, and S.P. Tucker (eds.). Laboratory Decontamination and Destruction of Carcinogens in Laboratory Wastes: Some Polycyclic Aromatic Hydrocarbons. IARC Publications No. 49. Lyon, France: International Agency for Research on Cancer, 1983., p. 45] **PEER REVIEWED** Absorption maxima (nm) (molar extraction): Solvent: benzene: 385 (1096), 359 (5754), 344 (7943), 329 (7943), 316 (5011), 290 (125892), 280 (89125), 267 (46773), 254 (41687), 227 (43652), 222 (45709).[Castegnaro, M., G. Grimmer, O. Hutzinger, W. Karcher, H. Kunte, M. LaFontaine, E.B. Sansone, G. Telling, and S.P. Tucker (eds.). Laboratory Decontamination and Destruction of Carcinogens in Laboratory Wastes: Some Polycyclic Aromatic Hydrocarbons. IARC Publications No. 49. Lyon, France: International Agency for Research on Cancer, 1983., p. 46] **PEER REVIEWED** Maximum absorption (cyclohexane): 219, 226, 254, 265, 272, 283, 296, 330, 345, 363, 379, 383, 393, 402 nm[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume

work). Available at: http://monographs.iarc.fr/index.php, p. V32 212 (1983)] **PEER REVIEWED** Intense mass spectral peaks: 252 m/z (100%), 126 m/z (23%), 253 m/z (21%), 250 m/z (16%)[Hites, R.A. Handbook of Mass Spectra of Environmental Contaminants. Boca Raton, FL: CRC Press Inc., 1985., p. 62] **PEER REVIEWED** IR: 8245 (Sadtler Research Laboratories IR grating collection)[Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V2: 1289] **PEER REVIEWED** UV: 594 (Sadtler Research Laboratories Spectral Collection)[Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V2: 1289] **PEER REVIEWED** 1H NMR: 704 (Sadtler Research Laboratories spectral collection)[Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V2: 1289] **PEER REVIEWED** MASS: 107138 (NIST/EPA/MSDC Mass Spectral Database, 1990 Version); 1756 (Atlas of Mass Spectral Data, John Wiley &amp; Sons, New York)[Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V2: 1289] **PEER REVIEWED** VAPOR DENSITY: 8.7 (Air = 1)[Warshawsky D; Patty's Toxicology. (2007). NY, NY: John Wiley &amp; Sons, Inc. Polycyclic and Heterocyclic Aromatic Hydrocarbons. On-line posting date: December 4, 2000.] **PEER REVIEWED** VAPOR PRESSURE: 5.49X10-9 mm Hg at 25 deg C /extrapolated value/[Murray JJ et al; Can J Chem 52: 557-63 (1974)] **PEER REVIEWED** OTHER CHEMICAL/PHYSICAL PROPERTIES: 1 PPM IS EQUIVALENT TO 10.32 MG/CU M (WT/VOL)[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 3346] **PEER REVIEWED** Dilute benzene solutions exhibit violet fluorescence[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 183] **PEER REVIEWED** Oxidation of a solution of /benzo(a)pyrene/ in acetone by Milas reagent (dilution of hydrogen peroxide to 20-40% with tert-butanol and addition of 1-2% osmium tetroxide in tert-butanol) leads to production of 2,8-,5,10-, and 6,7-quinones.[Castegnaro, M., G. Grimmer, O. Hutzinger, W. Karcher, H. Kunte, M. LaFontaine, E.B. Sansone, G. Telling, and S.P. Tucker (eds.). Laboratory Decontamination and Destruction of Carcinogens in Laboratory Wastes: Some Polycyclic Aromatic Hydrocarbons. IARC Publications No. 49. Lyon, France: International Agency for Research on Cancer, 1983., p. 54] **PEER REVIEWED** Oxidation /of benzo(a)pyrene/ in presence of pyridine in acetonitrile, using tetraethylammonium perchlorate as electrolyte, leads to N-(6-benzo[a]pyrenyl) pyridinium salt in high yield.[Castegnaro, M., G. Grimmer, O. Hutzinger, W. Karcher, H. Kunte, M. LaFontaine, E.B. Sansone,

G. Telling, and S.P. Tucker (eds.). Laboratory Decontamination and Destruction of Carcinogens in Laboratory Wastes: Some Polycyclic Aromatic Hydrocarbons. IARC Publications No. 49. Lyon, France: International Agency for Research on Cancer, 1983., p. 53] **PEER REVIEWED** Oxidation with ozone yields benzo(a)pyrene-(1,6 or 3,6)-quinone, &amp;, on further oxidation, benzanthrone dicarboxylic anhydride. Readily undergoes nitration &amp; halogenation. Reacts with NO /nitric oxide/ &amp; NO2 /nitrogen dioxide/ to form nitro derivatives.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V32 212 (1983)] **PEER REVIEWED** Benzo(a)pyrene dissolved in benzene was irradiated by ultraviolet light of a wavelength greater than 280 mu. Oxygen was present in the benzene. ... /Three crystalline/ compounds /were identified/ as 6,12-benzo(a)pyrenequinone, 1,6-benzo(a)pyrenequinone, and 3,6-benzo(a)pyrenequinone.[Masuda Y, Kuratsune M; Air &amp; Water Pollut Int J 10: 805-11 (1966)] **PEER REVIEWED** Forms a picrate (dark red needles from benzene) and a red complex with 1,3,5-trinitrobenzene[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V3 92 (1973)] **PEER REVIEWED** Heat of fusion: 15.69 cal/g (65.65 J/g; 16,564 J/mol)[Lide, D.R. CRC Handbook of Chemistry and Physics 88TH Edition 2007-2008. CRC Press, Taylor &amp; Francis, Boca Raton, FL 2007, p. 6-124] **PEER REVIEWED** Boiling point: > 360 deg C at 760 mm Hg[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 3] **PEER REVIEWED** Undergoes photooxidation after irradiation in indoor sunlight or by fluorescent light in organic solvents.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V32 212 (1983)] **PEER REVIEWED** Adsorption and fluorescent spectra, fluorescent quantum yields, decay times, and O quenching constants of benzo(a)pyrene and benzo(e)pyrene, benzo(b)fluoranthene, benzo(j)fluoranthene, benzo(k)fluoranthene, indleno(1,2,3-cd)pyrene, benzo(a)anthracene, and cyclopenta(cd)pyrene, and of other airborne polycyclic aromatic hydrocarbons (PAH) were measured with and without oxygen in heptane at room temperature. ... This data can be used for optimal analysis of PAH by fluorescence spectrometry. The differences in the oxygen quenching of the fluorescent state of the various PAH can be used to analyze PAH mixtures which are difficult to separate by chromatographic techniques.[Heinrich G, Guesten H; Polynucl Aromat Hydrocarbons: Chem Biol Eff Int Symp 4th 983-1003 (1980)] **PEER REVIEWED** Henry's Law constant = 4.57X10-7 atm-cu m/mole at 25 deg C[Ten Hulscher TEM et al; Environ Toxicol Chem 11: 1595-603 (1992)] **PEER REVIEWED**

Hydroxyl radical reaction rate constant = 5.0X10-11 cu cm/molec-sec at 25 deg C (est)[US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.0. Jan, 2009. Available from, as of August 31, 2009: http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm] **PEER REVIEWED** CHEMICAL SAFETY & HANDLING: SKIN, EYE AND RESPIRATORY IRRITATIONS: BaP can cause exposure by inhalation and passing through the unbroken skin. Can cause skin irritation with rash and/or burning sensations. Exposure to sunlight can increase these effects. Eye contact can cause irritations and burns.[Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 2002. 4th ed.Vol 1 A-H Norwich, NY: Noyes Publications, 2002., p. 326] **PEER REVIEWED** FIRE POTENTIAL: Combustible.[International Program on Chemical Safety/Commission of the European Communities; International Chemical Safety Card on Benzo(a)pyrene (October 2005). Available from, as of November 17, 2009: http://www.inchem.org/pages/icsc.html] **PEER REVIEWED** NFPA HAZARD CLASSIFICATION: Health 2, Flammability 1, Reactivity 0[Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 2002. 4th ed.Vol 1 A-H Norwich, NY: Noyes Publications, 2002., p. 325] **PEER REVIEWED** FIRE FIGHTING PROCEDURES: Flammable, but generally found in such low quantities it is not considered a fire hazard ... Poisonous gases are produced in fire including carbon monoxide. If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters. Notify local health and fire officials and pollution control agencies. From a secure, explosion-proof location, use water spray to cool exposed containers. If cooling streams are ineffective (venting sound increases in volume and pitch, tank discolors or shows any signs of deforming), withdraw immediately to a secure position.[Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 2002. 4th ed.Vol 1 A-H Norwich, NY: Noyes Publications, 2002., p. 326] **PEER REVIEWED** If material on fire or involved in fire: Extinguish fire using agent suitable for type of surrounding fire (material itself does not burn or burns with difficulty). Use dry chemical, dry sand, or carbon dioxide. Keep run-off water out of sewers and water sources.[Association of American Railroads; Bureau of Explosives. Emergency Handling of Hazardous Materials in Surface Transportation. Association of American Railroads, Pueblo, CO. 2005, p. 116] **PEER REVIEWED** Fire Fighting: Self-contained breathing apparatus with a full facepiece operated in pressure-demand or other positive pressure mode. /Coal tar pitch volatiles/[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 6] **PEER REVIEWED** Extinguishant: Foam, dry chemical, and carbon dioxide. /Coal tar pitch volatiles/[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards.

DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 3] **PEER REVIEWED** HAZARDOUS REACTIVITIES & INCOMPATIBILITIES: Incompatibilities: strong oxidizers, nitrogen dioxide, and ozone.[Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 2002. 4th ed.Vol 1 A-H Norwich, NY: Noyes Publications, 2002., p. 325] **PEER REVIEWED** The chemical is nonflammable but is incompatible with strong oxidizers.[Harris, R.L. (Ed.). Patty's Industrial Hygiene. Volumes 1-4. 5th Edition. John Wiley &amp; Sons, New York, N.Y. (2000).] **PEER REVIEWED** HAZARDOUS DECOMPOSITION: When heated to decomposition it emits acrid smoke and fumes.[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley &amp; Sons, Inc. Hoboken, NJ. 2004., p. 384] **PEER REVIEWED** IMMEDIATELY DANGEROUS TO LIFE OR HEALTH: 80 mg/cu m; NIOSH considers coal tar pitch volatiles to be potential occupational carcinogens. /Coal tar pitch volatiles/[NIOSH. NIOSH Pocket Guide to Chemical Hazards &amp; Other Databases CD-ROM. Department of Health &amp; Human Services, Centers for Disease Prevention &amp; Control. National Institute for Occupational Safety &amp; Health. DHHS (NIOSH) Publication No. 2005-151 (2005)] **PEER REVIEWED** PROTECTIVE EQUIPMENT & CLOTHING: Wear protective gloves and clothing to prevent any reasonable probability of skin contact ... Contact lenses should not be worn when working with this chemical. Wear dust-proof chemical goggles and face shield unless full faceplate respiratory protection is worn ... Provide emergency showers and eyewash.[Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 2002. 4th ed.Vol 1 A-H Norwich, NY: Noyes Publications, 2002., p. 326] **PEER REVIEWED** When benzo[a]pyrene-containing products are handled, protective garments should be worn, and adequate ventilation and respiratory equipment should be available.[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 3365] **PEER REVIEWED** Employees should be provided with and required to use impervious clothing, gloves, face-shields (eight-inch minimum), and other appropriate protective clothing necessary to prevent any possibility of skin contact with coal tar pitch volatiles. Employees should be provided with and required to use splash-proof goggles where there is any possibility of liquid coal tar volatiles contacting the eyes. /Coal tar pitch volatiles/[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 3] **PEER REVIEWED** PRECAUTIONS FOR "CARCINOGENS": ... dispensers of liq detergent /should be available/ ... Safety pipettes should be used for all pipetting ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece and close-fitting at ankles and wrists), gloves, hair covering and overshoes ... In chemical laboratory, gloves &amp; gowns should always be worn ... however, gloves should not be assumed to provide

full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, and disposable plastic aprons might provide addnl protection. ... gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979., p. 8] **PEER REVIEWED** Respirator Recommendations: At concentrations above the NIOSH REL, or where there is no REL, at any detectable concentration: /Coal tar pitch volatiles/ Assigned Protection Factor (APF) Respirator Recommendation APF = 50 Any self-contained breahting apparatus with a full-facepiece APF = 2,000 Any supplied-air-respirator that has a full facepiece and is operated in a pressure-demand or other positive pressure mode. APF = 10,000 Any supplied-air-respirator that has a full-facepiece and is operated in a pressure-demand or other positive-pressure mode in combination with an auxiliary self-contained breathing apparatus operated in pressure-demand or other positive-pressure mode. [NIOSH. NIOSH Pocket Guide to Chemical Hazards &amp; Other Databases CD-ROM. Department of Health &amp; Human Services, Centers for Disease Prevention &amp; Control. National Institute for Occupational Safety &amp; Health. DHHS (NIOSH) Publication No. 2005-151 (2005)] **PEER REVIEWED** Respirator Recommendations: Escape conditions: /Coal tar pitch volatiles/ Assigned Protection Factor (APF) Respirator Recommendation APF = 50 Any air-purifying, full-facepiece repirator (gas mask) with a chin-style, front- or back-mounted organic vapor canister in combination with an N100, R100, or P100 filter. Any appropriate escape-type, self-contained breathing apparatus. [NIOSH. NIOSH Pocket Guide to Chemical Hazards &amp; Other Databases CD-ROM. Department of Health &amp; Human Services, Centers for Disease Prevention &amp; Control. National Institute for Occupational Safety &amp; Health. DHHS (NIOSH) Publication No. 2005-151 (2005)] **PEER REVIEWED** PREVENTIVE MEASURES: If material not on fire and not involved in fire: Keep sparks, flames, and other sources of ignition away. Keep material out of water sources and sewers. Build dikes to contain flow as necessary.[Association of American Railroads; Bureau of Explosives. Emergency Handling of Hazardous Materials in Surface Transportation. Association of American Railroads, Pueblo, CO. 2005, p. 116] **PEER REVIEWED** Personnel protection: Avoid breathing vapors or dusts. Do not handle broken packages unless wearing appropriate personal protective equipment. Avoid breathing dusts fumes from burning material.[Association of American Railroads; Bureau of Explosives. Emergency Handling of Hazardous Materials in Surface Transportation. Association of American Railroads, Pueblo, CO. 2005, p. 116] **PEER REVIEWED** SRP: The scientific literature for the use of contact lenses in industry is conflicting. The benefit or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In

any event, the usual eye protection equipment should be worn even when contact lenses are in place. **PEER REVIEWED** SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker. **PEER REVIEWED** SRP: Contaminated protective clothing should be segregated in a manner so that results in no direct personal contact by personnel who handle, dispose of, or clean the clothing. Quality assurance procedures to confirm the efficacy of the cleaning procedures should be implemented prior to the decontaminated protective clothing being returned for reuse by the workers. Contaminated clothing (including shoes/socks) should not be taken home at end of shift, but should remain at employee's place of work for cleaning. **PEER REVIEWED** PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food &amp; beverage containers or utensils, &amp; the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, &amp; rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979., p. 8] **PEER REVIEWED** PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes &amp; wear protective suits (preferably disposable, one-piece &amp; close-fitting at ankles &amp; wrists), gloves, hair covering &amp; overshoes. ... clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. In chemical laboratory, gloves &amp; gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, &amp; disposable plastic aprons might provide addnl protection. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979., p. 8] **PEER REVIEWED** PRECAUTIONS FOR "CARCINOGENS": ... operations connected with synth &amp; purification ... should be carried out under well-ventilated hood. Analytical procedures ... should be carried out with care &amp; vapors evolved during ... procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... &amp; when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so that carcinogenic powders can be

handled without ... powder being blown around the hood. Glove boxes should be kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will not occur. /Chemical Carcinogens/[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979., p. 8] **PEER REVIEWED** PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological safety cabinets may be used for containment of in vitro procedures ... provided that the exhaust air flow is sufficient to provide an inward air flow at the face opening of the cabinet, &amp; contaminated air plenums that are under positive pressure are leak-tight. Horizontal laminar-flow hoods or safety cabinets, where filtered air is blown across the working area towards the operator, should never be used ... Each cabinet or fume cupboard to be used ... should be tested before work is begun (eg, with fume bomb) &amp; label fixed to it, giving date of test &amp; avg air-flow measured. This test should be repeated periodically &amp; after any structural changes. /Chemical Carcinogens/[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979., p. 9] **PEER REVIEWED** PRECAUTIONS FOR "CARCINOGENS": Principles that apply to chem or biochem lab also apply to microbiological &amp; cell-culture labs. ... Special consideration should be given to route of admin. ... Safest method of admin volatile carcinogen is by injection of a soln. Admin by topical application, gavage, or intratracheal instillation should be performed under hood. If chem will be exhaled, animals should be kept under hood during this period. Inhalation exposure requires special equipment. ... unless specifically required, routes of admin other than in the diet should be used. Mixing of carcinogen in diet should be carried out in sealed mixers under fume hood, from which the exhaust is fitted with an efficient particulate filter. Techniques for cleaning mixer &amp; hood should be devised before expt begun. When mixing diets, special protective clothing &amp;, possibly, respirators may be required. /Chemical Carcinogens/[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979., p. 9] **PEER REVIEWED** PRECAUTIONS FOR "CARCINOGENS": When ... admin in diet or applied to skin, animals should be kept in cages with solid bottoms &amp; sides &amp; fitted with a filter top. When volatile carcinogens are given, filter tops should not be used. Cages which have been used to house animals that received carcinogens should be decontaminated. Cage-cleaning facilities should be installed in area in which carcinogens are being used, to avoid moving of ... contaminated /cages/. It is difficult to ensure that cages are decontaminated, &amp; monitoring methods are necessary. Situations may exist in which the use of disposable cages should be recommended, depending on type &amp; amt of carcinogen &amp; efficiency with which it can be removed. /Chemical Carcinogens/[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979., p. 10] **PEER

REVIEWED** PRECAUTIONS FOR "CARCINOGENS": To eliminate risk that ... contamination in lab could build up during conduct of expt, periodic checks should be carried out on lab atmospheres, surfaces, such as walls, floors &amp; benches, &amp; ... interior of fume hoods &amp; airducts. As well as regular monitoring, check must be carried out after cleaning-up of spillage. Sensitive methods are required when testing lab atmospheres for chem such as nitrosamines. Methods ... should ... where possible, be simple &amp; sensitive. ... /Chemical Carcinogens/[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979., p. 10] **PEER REVIEWED** PRECAUTIONS FOR "CARCINOGENS": Rooms in which obvious contamination has occurred, such as spillage, should be decontaminated by lab personnel engaged in expt. Design of expt should ... avoid contamination of permanent equipment. ... Procedures should ensure that maintenance workers are not exposed ... Particular care should be taken to avoid contamination of drains or ventilation ducts. In cleaning labs, procedures should be used which do not produce aerosols or dispersal of dust, ie, wet mop or vacuum cleaner equipped with high-efficiency particulate filter on exhaust, which are avail commercially, should be used. Sweeping, brushing &amp; use of dry dusters or mops should be prohibited. ... contaminated cleaning materials should not be re-used ... If gowns or towels are contaminated, they should not be sent to laundry, but ... decontaminated or burnt, to avoid any hazard to laundry personnel. /Chemical Carcinogens/[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979., p. 10] **PEER REVIEWED** PRECAUTIONS FOR "CARCINOGENS": Doors leading into areas where carcinogens are used ... should be marked distinctively with appropriate labels. Access ... limited to persons involved in expt. ... A prominently displayed notice should give the name of the Scientific Investigator or other person who can advise in an emergency &amp; who can inform others (such as firemen) on the handling of carcinogenic substances. /Chemical Carcinogens/[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979., p. 11] **PEER REVIEWED** Wear appropriate eye protection to prevent eye contact. /Coal tar pitch volatiles/[NIOSH. NIOSH Pocket Guide to Chemical Hazards &amp; Other Databases CD-ROM. Department of Health &amp; Human Services, Centers for Disease Prevention &amp; Control. National Institute for Occupational Safety &amp; Health. DHHS (NIOSH) Publication No. 2005-151 (2005), p. 74] **PEER REVIEWED** Wear appropriate personal protective clothing to prevent skin contact.. /Coal tar pitch volatiles/[NIOSH. NIOSH Pocket Guide to Chemical Hazards &amp; Other Databases CD-ROM. Department of Health &amp; Human Services, Centers for Disease Prevention &amp; Control. National Institute for Occupational Safety &amp; Health. DHHS (NIOSH) Publication No. 2005-151 (2005), p. 74] **PEER REVIEWED**

The worker should wash daily at the end of each work shift, and prior to eating, drinking, smoking, etc. /Coal tar pitch volatiles/[NIOSH. NIOSH Pocket Guide to Chemical Hazards &amp; Other Databases CD-ROM. Department of Health &amp; Human Services, Centers for Disease Prevention &amp; Control. National Institute for Occupational Safety &amp; Health. DHHS (NIOSH) Publication No. 2005-151 (2005), p. 74] **PEER REVIEWED** Workers whose clothing may have become contaminated should change into uncontaminated clothing before leaving the work premises.. /Coal tar pitch volatiles/[NIOSH. NIOSH Pocket Guide to Chemical Hazards &amp; Other Databases CD-ROM. Department of Health &amp; Human Services, Centers for Disease Prevention &amp; Control. National Institute for Occupational Safety &amp; Health. DHHS (NIOSH) Publication No. 2005-151 (2005), p. 74] **PEER REVIEWED** STABILITY/SHELF LIFE: Undergoes photo-oxidation after irradiation in indoor sunlight or by fluorescent light in organic solvents.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V32 212 (1983)] **PEER REVIEWED** B(a)P is light labile &amp; is oxidized by chromic acid &amp; by ozone.[National Research Council. Prudent Practices for Handling Hazardous Chemicals in Laboratories. Washington, DC: National Academy Press, 1981., p. 51] **PEER REVIEWED** STORAGE CONDITIONS: Store in tightly closed containers in a cool, well-ventilated area away from oxidizing chemicals (such as chlorates, perchlorates, permanganates, and nitrates). A regulated, marked area should be established where this chemical is handled, used, or stored in compliance with OSHA standard 1910.1045.[Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 2002. 4th ed.Vol 1 A-H Norwich, NY: Noyes Publications, 2002., p. 326] **PEER REVIEWED** PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practicable to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen &amp; date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979., p. 13] **PEER REVIEWED** CLEANUP METHODS: SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will

not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal. **PEER REVIEWED** Evacuate and restrict persons not wearing protective equipment from area of spill or leak until cleanup is complete. Remove all ignition sources. Collect powdered material in the most convenient and safe manner and deposit in sealed containers. Ventilate area of spill or leak after cleanup is complete. It may be necessary to contain and dispose of this chemical as a hazardous waste. If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters.[Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 2002. 4th ed.Vol 1 A-H Norwich, NY: Noyes Publications, 2002., p. 326] **PEER REVIEWED** Land spill: Dig a pit, pond, lagoon, holding area to contain liquid or solid material. /SRP: If time permits, pits, ponds, lagoons, soak holes, or holding areas should be sealed with an impermeable flexible membrane liner./ Cover solids with a plastic sheet to prevent dissolving in rain or fire fighting water. Dike surface flow using soil, sand bags, foamed polyurethane, or foamed concrete.[Association of American Railroads; Bureau of Explosives. Emergency Handling of Hazardous Materials in Surface Transportation. Association of American Railroads, Pueblo, CO. 2005, p. 114] **PEER REVIEWED** Water spill: Use natural barriers or oil spill control booms to limit spill travel. Use natural deep water pockets, excavated lagoons, or sand bag barriers to trap material at bottom. Remove trapped material with suction hoses.[Association of American Railroads; Bureau of Explosives. Emergency Handling of Hazardous Materials in Surface Transportation. Association of American Railroads, Pueblo, CO. 2005, p. 114] **PEER REVIEWED** Air spill: Apply water spray or mist to knock down vapors.[Association of American Railroads; Bureau of Explosives. Emergency Handling of Hazardous Materials in Surface Transportation. Association of American Railroads, Pueblo, CO. 2005, p. 116] **PEER REVIEWED** Do NOT let this chemical enter the environment. Sweep spilled substance into sealable containers; if appropriate, moisten first to prevent dusting. Carefully collect remainder, then remove to safe place.[International Program on Chemical Safety/Commission of the European Communities; International Chemical Safety Card on Benzo(a)pyrene (October 2005). Available from, as of November 17, 2009: http://www.inchem.org/pages/icsc.html] **PEER REVIEWED** This method incorporates procedures for the destruction of laboratory wastes contaminated with PAH using an aqueous saturated potassium permanganate solution. This method has been tested for wastes contaminated with the following PAH: Benz(a)anthracene, 7,12-dimethylbenz(a)anthracene, benzo(a)pyrene, 3-methylcholanthrene, and 7-bromomethylbenz(a)anthracene. It has been studied collaboratively with a solution of benz(a)anthracene + benzo(a)pyrene + 7,12-dimenthylbenz(a)anthracene and a solution of 3-methylcholanthrene + dibenz(a,h)anthracene in cyclohexane. The method affords better than 95% destruction of all of the PAH tested except for dibenzo(a,h)anthracene, for which only variable and incomplete destruction could be achieved.[Castegnaro, M., G. Grimmer, O. Hutzinger, W. Karcher,

H. Kunte, M. LaFontaine, E.B. Sansone, G. Telling, and S.P. Tucker (eds.). Laboratory Decontamination and Destruction of Carcinogens in Laboratory Wastes: Some Polycyclic Aromatic Hydrocarbons. IARC Publications No. 49. Lyon, France: International Agency for Research on Cancer, 1983., p. 31] **PEER REVIEWED** Ten mL of a solution containing 0.3 mol/L of potassium permanganate and 3 mol/l of sulfuric acid will degrade 5 mg of benz[a]anthracene, benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene, dibenz[a,h]anthracene, 3-methylcholanthrene, or 7-bromomethylbenz[a]anthracene in acetone in 1 hr.[Castegnaro, M., G. Grimmer, O. Hutzinger, W. Karcher, H. Kunte, M. LaFontaine, E.B. Sansone, G. Telling, and S.P. Tucker (eds.). Laboratory Decontamination and Destruction of Carcinogens in Laboratory Wastes: Some Polycyclic Aromatic Hydrocarbons. IARC Publications No. 49. Lyon, France: International Agency for Research on Cancer, 1983., p. 19] **PEER REVIEWED** An oxidation method using a 16% (m/v) solution of potassium dichromate in 9 mol/L sulfuric acid. The method was tested collaboratively with a solution of benz[a]anthracene + benzo[a]pyrene + 7,12-dimethylbenz[a]anthracene and with a solution of 3-methylcholanthrene + dibenz[a,h]anthracene in cyclohexane. /The procedure/ resulted in more than 99% destruction. However, due to regulations in force in several countries which prohibit the discharge of chromate into sewage, the method was withdrawn.[Castegnaro, M., G. Grimmer, O. Hutzinger, W. Karcher, H. Kunte, M. LaFontaine, E.B. Sansone, G. Telling, and S.P. Tucker (eds.). Laboratory Decontamination and Destruction of Carcinogens in Laboratory Wastes: Some Polycyclic Aromatic Hydrocarbons. IARC Publications No. 49. Lyon, France: International Agency for Research on Cancer, 1983., p. 11] **PEER REVIEWED** The use of Cl2, ClO2, O3, and uv light for this purpose has been studied. 50-60% of benzo[a]pyrene can be removed by chlorination of water. ... ClO2 ... reduces benzo[a]pyrene concn by 90%. But at benzo(a)pyrene concentrations lower than 10 ppt, ClO2 no longer functions as an oxidant for the transformation of benzo[a]pyrene.[USEPA; Ambient Water Quality Criteria Doc: Polynuclear Aromatic Hydrocarbons (Draft) p.C-4 (1980)] **PEER REVIEWED** ... In surface waters, one-third of the total PAH is bound to larger suspended particles, a third is bound to finely dispersed particles, and the last third is present in dissolved form. The particle-bound portion of polycyclic aromatic hydrocarbons (PAH) can be removed by sedimentation, flocculation, and filtration processes. The remaining one-third dissolved PAH usually requires oxidation for partial removal/transformation. /polynuclear aromatic hydrocarbons/[USEPA; Ambient Water Quality Criteria Doc: Polynuclear Aromatic Hydrocarbons (Draft) p.C-4 (1980)] **PEER REVIEWED** PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured &amp; the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated

... The plastic bag should also be sealed &amp; labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979., p. 15] **PEER REVIEWED** DISPOSAL METHODS: Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U022, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.[40 CFR 240-280, 300-306, 702-799 (7/1/96)] **PEER REVIEWED** A good potential candidate for fluidized bed incineration at a temperature range of 450 to 980 deg C and residence times of seconds for liquids and gases, and longer for solids. Also, a good potential candidate for rotary kiln incineration at a temperature range of 820 to 1,600 deg C and residence times of seconds for liquids and gases, and hours for solids.[USEPA; Engineering Handbook for Hazardous Waste Incineration p.3-11 (1981) EPA 68-03-3025] **PEER REVIEWED** PRECAUTIONS FOR "CARCINOGENS": Total destruction ... by incineration may be only feasable method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable ... Most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous &amp; organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979., p. 15] **PEER REVIEWED** PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp &amp; carcinogenic wastes generated by this treatment conducted to &amp; burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter &amp; misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979., p. 15] **PEER REVIEWED** PRECAUTIONS FOR "CARCINOGENS": ... small quantities of ... some carcinogens can be destroyed using chem reactions ... but no general rules can be given. ... As a general technique ... treatment with sodium dichromate in strong sulfuric acid can be used. The time necessary for destruction ... is seldom known ... but 1-2 days is generally considered sufficient when freshly prepd reagent is used. ... /Oxidation method using

dichromate-sulfuric acid is specific for B(a)P/. Carcinogens that are easily oxidizable can be destroyed with milder oxidative agents, such as sat soln of potassium permanganate in acetone, which appears to be a suitable agent for destruction of hydrazines or of compounds containing isolated carbon-carbon double bonds. Concn or 50% aqueous sodium hypochlorite can also be used as an oxidizing agent. /Chemical Carcinogens/[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979., p. 16] **PEER REVIEWED** PRECAUTIONS FOR "CARCINOGENS": Carcinogens that are alkylating, arylating or acylating agents per se can be destroyed by reaction with appropriate nucleophiles, such as water, hydroxyl ions, ammonia, thiols &amp; thiosulfate. The reactivity of various alkylating agents varies greatly ... &amp; is also influenced by sol of agent in the reaction medium. To facilitate the complete reaction, it is suggested that the agents be dissolved in ethanol or similar solvents. ... No method should be applied ... until it has been thoroughly tested for its effectiveness &amp; safety on material to be inactivated. For example, in case of destruction of alkylating agents, it is possible to detect residual compounds by reaction with 4(4-nitrobenzyl)-pyridine. /Chemical Carcinogens/[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979., p. 17] **PEER REVIEWED** IARC describes laboratory decontamination &amp; destruction methods for polycyclic aromatic hydrocarbons in this publication (number 49). The method specifies procedures for destruction of benzo(a)pyrene using potassium permanganate under acidic conditions or concentrated sulfuric acid for the following wastes: pure cmpd, soln in org solvents (excluding dimethylformamide (DMF) &amp; dimethyl sulfoxide (DMSO)), soln in (DMF), soln in (DMSO, soln in oil, soln in water, glassware, petri dish contents &amp; spills.[Castegnaro, M., G. Grimmer, O. Hutzinger, W. Karcher, H. Kunte, M. LaFontaine, E.B. Sansone, G. Telling, and S.P. Tucker (eds.). Laboratory Decontamination and Destruction of Carcinogens in Laboratory Wastes: Some Polycyclic Aromatic Hydrocarbons. IARC Publications No. 49. Lyon, France: International Agency for Research on Cancer, 1983., p. 1] **PEER REVIEWED** Catalytic oxidation by bauxite-type catalyst at 400-600 deg C in the gas phase. Efficiency increases with temperature: 94% efficiency can be achieved. Reaction products: CO2 and water.[Castegnaro, M., G. Grimmer, O. Hutzinger, W. Karcher, H. Kunte, M. LaFontaine, E.B. Sansone, G. Telling, and S.P. Tucker (eds.). Laboratory Decontamination and Destruction of Carcinogens in Laboratory Wastes: Some Polycyclic Aromatic Hydrocarbons. IARC Publications No. 49. Lyon, France: International Agency for Research on Cancer, 1983., p. 54] **PEER REVIEWED** The method incorporates procedures for the destruction of laboratory wastes contaminated with PAH using concentrated sulfuric acid. The method has been tested for wastes contaminated with the following PAH: Benz(a)anthracene, 7,12-dimethylbenz(a)anthracene, benzo(a)pyrene, 3-methylcholanthrene, 7-bromomethylbenz(a)anthracene, and dibenz(a,h)anthracene. It has been studied collaboratively using solutions of benz(a)anthracene + benzo(a)pyrene + 7,12-dimethylbenz(a)anthracene and solutions of methylcholanthrene + dibenz(a,h)anthracene in DMF and DMSO.

... The method affords better than 99% destruction in all solutions tested.[Castegnaro, M., G. Grimmer, O. Hutzinger, W. Karcher, H. Kunte, M. LaFontaine, E.B. Sansone, G. Telling, and S.P. Tucker (eds.). Laboratory Decontamination and Destruction of Carcinogens in Laboratory Wastes: Some Polycyclic Aromatic Hydrocarbons. IARC Publications No. 49. Lyon, France: International Agency for Research on Cancer, 1983., p. 25] **PEER REVIEWED** Polycyclic aromatic hydrocarbons may be destroyed by oxidation with potassium permanganate in sulfuric acid (KMnO4 in H2SO4) or by dissolution in concentrated H2SO4. The solution of KMnO4 in H2SO4 should be freshly prepared by stirring the calculated amount of KMnO4 in H2SO4 for at least 15 min but no more than 1 hr. The products of these reactions have not been determined. Destruction efficiency was greater than 99% in each case. /Polycyclic aromatic hydrocarbons/[Lunn, G., E.B. Sansone. Destruction of Hazardous Chemicals in the Laboratory. New York, NY: John Wiley &amp; Sons, Inc. 1994., p. 349] **PEER REVIEWED** OCCUPATIONAL EXPOSURE STANDARDS: OSHA STANDARDS: Permissible Exposure Limit: Table Z-1 8-hr Time Weighted Avg: 0.2 mg/cu m. /Coal tar pitch volatiles (benzene soluble fraction), anthracene, BaP, phenanthrene, acridine, chrysene, pyrene/[29 CFR 1910.1000 (USDOL); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of August 19, 2009: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED** THRESHOLD LIMIT VALUES: Exposure by all routes should be carefully controlled to levels as low as possible.[American Conference of Governmental Industrial Hygienists. Threshold Limit Values of Chemical Substances and Biological Exposure Indices, ACGIH, Cincinnati, OH 2009, p. 13] **PEER REVIEWED** A2; Suspected human carcinogen.[American Conference of Governmental Industrial Hygienists. Threshold Limit Values of Chemical Substances and Biological Exposure Indices, ACGIH, Cincinnati, OH 2009, p. 13] **PEER REVIEWED** Biological Exposure Index (BEI): Determinant: 1-Hydroxypyrene (-HP) in urine (with hydrolysis); Sampling Time: end of shift at end of workweek. Biological monitoring should be considered for this compound based on the review; however, a specific BEI could not be determined due to insufficient data. /Polycyclic Aromatic Hydrocarbons/[American Conference of Governmental Industrial Hygienists. Threshold Limit Values of Chemical Substances and Biological Exposure Indices, ACGIH, Cincinnati, OH 2009, p. 105] **PEER REVIEWED** NIOSH RECOMMENDATIONS: Recommended Exposure Limit: 10 Hr Time-Weighted Avg: 0.1 mg/cu m (cyclohexane-extractable fraction). /Coal tar pitch volatiles/[NIOSH. NIOSH Pocket Guide to Chemical Hazards &amp; Other Databases CD-ROM. Department of Health &amp; Human Services, Centers for Disease Prevention &amp; Control. National Institute for Occupational Safety &amp; Health. DHHS (NIOSH) Publication No. 2005-151 (2005)] **PEER REVIEWED** NIOSH considers coal tar pitch volatiles to be potential occupational carcinogens. /Coal tar pitch volatiles/[NIOSH. NIOSH Pocket Guide to

Chemical Hazards &amp; Other Databases CD-ROM. Department of Health &amp; Human Services, Centers for Disease Prevention &amp; Control. National Institute for Occupational Safety &amp; Health. DHHS (NIOSH) Publication No. 2005-151 (2005)] **PEER REVIEWED** IMMEDIATELY DANGEROUS TO LIFE OR HEALTH: 80 mg/cu m; NIOSH considers coal tar pitch volatiles to be potential occupational carcinogens. /Coal tar pitch volatiles/[NIOSH. NIOSH Pocket Guide to Chemical Hazards &amp; Other Databases CD-ROM. Department of Health &amp; Human Services, Centers for Disease Prevention &amp; Control. National Institute for Occupational Safety &amp; Health. DHHS (NIOSH) Publication No. 2005-151 (2005)] **PEER REVIEWED** OTHER STANDARDS REGULATIONS AND GUIDELINES: Czechoslovakia, the concentration of benzo(a)pyrene should not exceed 100-200 ug/100 cu m in the atmosphere of coal and pitch coking plants.[Masek V; J Occup Med 13: 193-8 (1971)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/5572839?dopt=Abstract" target=new>PubMed Abstract USSR Ministry of Health in November 1972 set the Maximum allowable concentration (MAC) for benzo(a)pyrene for a working zone at 15 ug/100 cu m, and in February 1973, 0.1 ug/100 cu m as the MAC for benzo(a)pyrene in atmospheric air.[Health &amp; Welfare Canada; Polycyclic Aromatic Hydrocarbons p.104 (1979) Report No. 80-EHD-50] **PEER REVIEWED** MANUFACTURING/USE INFORMATION: MAJOR USES: ... Used extensively as a positive control in a variety of /laboratory mutagenicity and carcinogenicity/ short-term tests.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V32: 215 (1983)] **PEER REVIEWED** No commercial production or known use for /benzo[a]pyrene/[Warshawsky D; Patty's Toxicology. (2007). NY, NY: John Wiley &amp; Sons, Inc. Polycyclic and Heterocyclic Aromatic Hydrocarbons. On-line posting date: December 4, 2000.] **PEER REVIEWED** Research chemical[SRI] **PEER REVIEWED** Not used commercially in USA[SRI] **PEER REVIEWED** METHODS OF MANUFACTURING: Synthesis from pyrene and succinic anhydride.[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 183] **PEER REVIEWED** GENERAL MANUFACTURING INFORMATION: Benzo[a]pyrene occurs naturally in crude oils, shale oils, and coal tars, and is emitted with gases and fly ash from active volcanoes.[Harris, R.L. (Ed.). Patty's Industrial Hygiene. Volumes 1-4. 5th Edition. John Wiley &amp; Sons, New York, N.Y. (2000).] **PEER REVIEWED** Polycyclic Aromatic Hydrocarbons (PAHs) are a group of chemicals that are

formed during the incomplete burning of coal, oil, gas, wood, garbage, or other organic substances, such as tobacco and charbroiled meat. There are more than 100 different PAHs. PAHs generally occur as complex mixtures (for example, as part of combustion products such as soot), not as single compounds. PAHs usually occur naturally, but they can be manufactured as individual compounds for research purposes, however, not as the mixtures found in combustion products.[U.S. Dept Health &amp; Human Services/Agency for Toxic Substances &amp; Disease Registry; Toxicological Profile for Polycyclic Aromatic Hydrocarbons p.1 (August 1995) PB/95/264370. Available from, as of April 6, 2010: http://www.atsdr.cdc.gov/toxpro2.html#] **PEER REVIEWED** ... Isolation by fractionation ... by adsorption and fluorimetric determination ...[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 183] **PEER REVIEWED** Occurs as benzo[a]pyrene and benzo[e]pyrene.[Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley &amp; Sons, Inc. New York, NY 2007., p. 138] **PEER REVIEWED** Not commercially produced, except as analytical standard.[Richter S, Nagel R; Chemosphere 66: 603-610 (2007)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/16997349?dopt=Abstract" target=new>PubMed Abstract There is no commercial production or known use for /benzo(a)pyrene/. Benzo(a)pyrene occurs ubiquitously as a product of incomplete combustion and also occurs in fossil fuels.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V32: 212 (1983)] **PEER REVIEWED** FORMULATIONS/PREPARATIONS: A reference material of certified high purity is available[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V32 212] **PEER REVIEWED** U. S. PRODUCTION: (1978) Not produced commercially in USA[SRI] **PEER REVIEWED** (1982) Not produced commercially in USA[SRI] **PEER REVIEWED** Not produced commercially in the USA.[IARC monographs 1972-Present V32 p.212] **PEER REVIEWED** LABORATORY METHODS: CLINICAL LABORATORY METHODS: Method: NOAA-NST 130.31; Procedure: gas chromatography mass spectrometry in the selected ion monitoring (SIM) mode; Analyte: benzo(a)pyrene; Matrix: marine animal tissues; Detection Limit: 4 ng/g.[National Environmental Methods Index; Analytical, Test and Sampling Methods. Benzo(a)pyrene (50-32-8). Available from, as of September 24, 2009: http://www.nemi.gov] **PEER REVIEWED**

Type of sample: animal tissue; extraction and cleanup sublimation or soxhlet extraction with benzene or cyclohexane; final separation and quantitation: TLC/fluorescence with a detection limit of 1.1 ng. /From table/[Health &amp; Welfare Canada; Polycyclic Aromatic Hydrocarbons p.15 (1979) Report No. 80-EHD-50] **PEER REVIEWED** HIGH PERFORMANCE LIQUID CHROMATOGRAPHY (REVERSE PHASE) ANALYSIS OF POLYCYCLIC AROMATIC HYDROCARBONS IN SKIN LIPIDS. /POLYCYCLIC AROMATIC HYDROCARBONS/[WOLFF MS ET AL; CHEMOSPHERE 11 (6): 595 (1982)] **PEER REVIEWED** ANALYTIC LABORATORY METHODS: Method: USGS-NWQL O-5505-03; Procedure: gas chromatography/mass spectrometry; Analyte: benzo(a)pyrene; Matrix: soil and sediment samples containing at least 10 ug/kg of analyte; Detection Limit: 1.8 ug/kg.[National Environmental Methods Index; Analytical, Test and Sampling Methods. Benzo(a)pyrene (50-32-8). Available from, as of September 24, 2009: http://www.nemi.gov] **PEER REVIEWED** Method: USGS-NWQL O-5130-95; Procedure: high-performance gel permeation chromatography, capillary-column GC/MS; Analyte: benzo(a)pyrene; Matrix: soils and sediment; Detection Limit: 17.1 ug/kg.[National Environmental Methods Index; Analytical, Test and Sampling Methods. Benzo(a)pyrene (50-32-8). Available from, as of September 24, 2009: http://www.nemi.gov] **PEER REVIEWED** Method: USGS-NWQL O-3113; Procedure: high performance liquid chromatography with ultraviolet detector; Analyte: benzo(a)pyrene; Matrix: water and water-suspended-sediment mixtures; Detection Limit: 1 ug/L.[National Environmental Methods Index; Analytical, Test and Sampling Methods. Benzo(a)pyrene (50-32-8). Available from, as of September 24, 2009: http://www.nemi.gov] **PEER REVIEWED** Method: USGS-NWQL O-1433-01; Procedure: gas chromatography/mass spectrometry; Analyte: benzo(a)pyrene; Matrix: filtered wastewater and natural-water samples; Detection Limit: 0.08 ug/L.[National Environmental Methods Index; Analytical, Test and Sampling Methods. Benzo(a)pyrene (50-32-8). Available from, as of September 24, 2009: http://www.nemi.gov] **PEER REVIEWED** Method: Standard Methods 6440B; Procedure: high performance liquid chromatography or gas chromatography with flame ionization detector; Analyte: benzo(a)pyrene; Matrix: municipal and industrial discharges; Detection Limit: 0.02 ug/L.[National Environmental Methods Index; Analytical, Test and Sampling Methods. Benzo(a)pyrene (50-32-8). Available from, as of September 24, 2009: http://www.nemi.gov] **PEER REVIEWED** Method: Standard Methods 6410B; Procedure: gas chromatography/mass spectrometry; Analyte: benzo(a)pyrene; Matrix: municipal and industrial discharges; Detection Limit: 2.5 ug/L.[National Environmental Methods Index; Analytical, Test and Sampling Methods. Benzo(a)pyrene (50-32-8). Available from, as of September 24, 2009: http://www.nemi.gov] **PEER REVIEWED** Method: NOAA-NST 130.30; Procedure: gas chromatography mass spectrometry in the selected ion monitoring (SIM) mode; Analyte: benzo(a)pyrene; Matrix: soils/sediment; Detection Limit: 0.3 ng/g.[National Environmental Methods Index; Analytical, Test and Sampling Methods. Benzo(a)pyrene (50-32-8). Available from, as of September 23, 2009: http://www.nemi.gov]

**PEER REVIEWED** Method: EPA-OSW 8310; Procedure: high performance liquid chromatography with ultraviolet and fluorescence detectors; Analyte: benzo(a)pyrene; Matrix: ground water and wastes; Detection Limit: 0.02 ug/L.[National Environmental Methods Index; Analytical, Test and Sampling Methods. Benzo(a)pyrene (50-32-8). Available from, as of September 24, 2009: http://www.nemi.gov] **PEER REVIEWED** Method: EPA-OSW 8270D; Procedure: gas chromatography/mass spectrometry; Analyte: benzo(a)pyrene; Matrix: solid waste matrices, soils, air sampling media and water samples; Detection Limit: not provided.[National Environmental Methods Index; Analytical, Test and Sampling Methods. Benzo(a)pyrene (50-32-8). Available from, as of September 24, 2009: http://www.nemi.gov] **PEER REVIEWED** Method: EPA-OSW 8100; Procedure: gas chromatography and flame ionization detection; Analyte: benzo(a)pyrene; Matrix: water and solid samples; Detection Limit: not provided.[National Environmental Methods Index; Analytical, Test and Sampling Methods. Benzo(a)pyrene (50-32-8). Available from, as of September 24, 2009: http://www.nemi.gov] **PEER REVIEWED** Method: EPA-NERL 625; Procedure: gas chromatography/mass spectrometry; Analyte: benzo(a)pyrene; Matrix: municipal and industrial discharges; Detection Limit: 2.5 ug/L.[National Environmental Methods Index; Analytical, Test and Sampling Methods. Benzo(a)pyrene (50-32-8). Available from, as of September 24, 2009: http://www.nemi.gov] **PEER REVIEWED** Method: EPA-NERL 525.2; Procedure: gas chromatography/mass spectrometry; Analyte: benzo(a)pyrene; Matrix: finished drinking water, source water, or drinking water in any treatment stage; Detection Limit: 0.032 ug/L.[National Environmental Methods Index; Analytical, Test and Sampling Methods. Benzo(a)pyrene (50-32-8). Available from, as of September 24, 2009: http://www.nemi.gov] **PEER REVIEWED** Method: EPA/NERL 550; Procedure: high performance liquid chromatography system equipped with ultraviolet absorption and fluorescence detectors; Analyte: benzo(a)pyrene; Matrix: drinking water sources and finished drinking water; Detection Limit: 0.029 ug/L.[National Environmental Methods Index; Analytical, Test and Sampling Methods. Benzo(a)pyrene (50-32-8). Available from, as of September 24, 2009: http://www.nemi.gov] **PEER REVIEWED** Method: EPA-EAD 1625; Procedure: gas chromatography/mass spectrometry; Analyte: benzo(a)pyrene; Matrix: water; Detection Limit: 10 ug/L.[National Environmental Methods Index; Analytical, Test and Sampling Methods. Benzo(a)pyrene (50-32-8). Available from, as of September 24, 2009: http://www.nemi.gov] **PEER REVIEWED** Method: EPA-EAD 610; Procedure: high performance liquid chromatography with ultraviloet and fluoresence detectors or gas chromatography with flame ionization detector; Analyte: benzo(a)pyrene; Matrix: municipal and industrial discharges; Detection Limit: 0.02 ug/L.[National Environmental Methods Index; Analytical, Test and Sampling Methods. Benzo(a)pyrene (50-32-8). Available from, as of September 24, 2009: http://www.nemi.gov] **PEER REVIEWED** Method: DOE OM100R; Procedure: gas chromatography/mass spectrometry; Analyte: benzo(a)pyrene; Matrix: solid waste matrices, soils, and groundwater; Detection Limit: 62 ug/L.[National Environmental Methods

Index; Analytical, Test and Sampling Methods. Benzo(a)pyrene (50-32-8). Available from, as of September 24, 2009: http://www.nemi.gov] **PEER REVIEWED** Method: NIOSH 5515, Issue 2; Procedure: gas chromatography, capillary column, flame ioniaztion detection; Analyte: benzo(a)pyrene; Matrix: air; Detection Limit: 0.3 to 0.5 ug /sample.[CDC; NIOSH Manual of Analytical Methods, 4th ed. Benzo(a)pyrene (50-32-8). Available from, as of September 28, 2009: http://www.cdc.gov/niosh/docs/2003-154/] **PEER REVIEWED** Method: NIOSH 5506, Issue 3; Procedure: high performance liquid chromatography with fluorescence detection; Analyte: benzo(a)pyrene; Matrix: air; Detection Limit: 0.0060-0.80 ug/sample.[CDC; NIOSH Manual of Analytical Methods, 4th ed. Benzo(a)pyrene (50-32-8). Available from, as of September 28, 2009: http://www.cdc.gov/niosh/docs/2003-154/] **PEER REVIEWED** ANALYTICAL METHOD INVOLVING SINGLE TLC SEPARATION OF CYCLOHEXANE-SOLUBLE FRACTION OF AIRBORNE PARTICULATE MATTER INTO 3 POLYCYCLIC AROMATIC HYDROCARBON FRACTIONS &amp; 1 ALIPHATIC HYDROCARBON FRACTION SUITABLE FOR GLC ANALYSIS IS DEVELOPED. METHOD IS SIMPLE, RAPID &amp; SUITABLE FOR ROUTINE ANALYSIS OF THESE COMPOUNDS IN AIRBORNE PARTICULATE MATTER. THE DIFFICULTY TO SEPARATE BENZOPYRENE &amp; BENZOFLUORANTHENE ISOMERS ARE COMPLETELY RESOLVED IN THE TLC SEPARATION.[DAISEY JM, LEYKO MA; ANAL CHEM 51 (1): 24-6 (1979)] **PEER REVIEWED** ULTRASONIC EXTRACTION OF AIRBORNE PARTICULATE MATERIAL ON HI-VOL FILTERS IS DESCRIBED. ALMOST ALL POLAR COMPOUNDS ARE REMOVED DURING EXTRACTION BY ADSORPTION ON THE SURFACE OF SHREDDED GLASS FIBERS &amp; CONTROLLED PORE GLASS POWDER (CPG). NON-POLAR POLYNUCLEAR AROMATIC HYDROCARBONS (PAH) IN THE EXTRACTS ARE SEPARATED AT ROOM TEMP BY HIGH PRESSURE LIQUID CHROMATOGRAPHY (HPLC) ON REVERSE PHASE VYDAC USING ACETONITRILE:WATER (70:30 VOL/VOL) AS CHROMATOGRAPHIC SOLVENT. B(A)P ELUTES IN APPROX 14 MIN. PRECISION &amp; ACCURACY MEASUREMENTS INDICATE FULL RECOVERY &amp; GOOD EXTRACTION REPRODUCIBILITY. DETECTION LIMIT FOR B(A)P AT F 290/389 IS LESS THAN 100 PG. TOTAL ANALYSIS TIME IS APPROX 1.5 HR.[GOLDEN C, SAWICKI E; ANAL LETT 11 (12): 1051-62 (1978)] **PEER REVIEWED** AOAC Method 973.30. Polycyclic Aromatic Hydrocarbons and Benzo(a)pyrene in Food. Spectrophotometric method. Benzo(a)pyrene is extracted from comminuted food sample after saponification with alcoholic potassium hydroxide, purified by solvent partition and column chromatography, separated by TLC, detected by UV spectrometry, and confirmed by spectrophotofluorometry.[Association of Official Analytical Chemists. Official Methods of Analysis. 15th ed. and Supplements. Washington, DC: Association of Analytical Chemists, 1990, p. 1176] **PEER REVIEWED** The X-ray excited optical luminescence (XEOL) of a concentrate in n-heptane of the neutral fraction isolated from by-products of coal combustion and conversion, and from shale and fuel oils was utilized to obtain profiles of their PAH content. Components which should be unequivocally identified include benzo(a)anthracene, BaP, benzo(e)pyrene, benzo(ghi)perylene, pyrene, benzo(k)fluoranthene, and coronene.[Fassel VA et al; Analytical Chem 52 (1): 159-64 (1980)] **PEER REVIEWED** Type of sample: maize; extraction and cleanup: soxhlet extraction with acetone/filtration over silica gel; final separation and quantitation: GLC/FID; with a detection limit of 0.25 ng.[Winkler EA et al; J Chromat 138: 151-64 (1977) as cited in Health &amp; Welfare Canada; Polycyclic Aromatic Hydrocarbons p.16 (1979) Report No. 80-EHD-50] **PEER REVIEWED**

Type of sample: atmospheric particulates; extraction and cleanup sublimation or soxhlet extraction with benzene or cyclohexane; final separation and quantitation: TLC/fluorescence with a detection limit of 1.1 ng. /From table/[Tomingas RG et al; Sci Total Environ 7: 261-7 (1977) as cited in Health &amp; Welfare Canada; Polycyclic Aromatic Hydrocarbons p.15 (1979) Report No. 80-EHD-50] **PEER REVIEWED** Contents of polycyclic aromatic hydrocarbons (PAHs) in the ointment and cosmetic bases liquid paraffin, yellow petrolatum, ichthammol and citric acid were determined by UV spectrophotometry (Japanese Pharmacopeia X), HPLC with fluorescence detection and TLC with fluorescence detection. The UV method gave poor results due to its low sensitivity and selectivity, whereas the HPLC method gave a good selectivity and quant results. TLC had an ability to detect PAHs and may be used in the detn of the PAH limit. Benzo(a)pyrene, benzo(e)pyrene, benzo(k)fluoranthene, benzo(b)fluoranthene, benzo(g,h,i)perylene and dibenz(a,h)anthracene were nondetectable in liquid paraffin and citric acid, and benzo(a)pyrene was not detected in ichthammol. Yellow petrolatum contained 0.2-1.75 ng/g benzo(a)pyrene in 3 samples analyzed.[Kawamura T, Nakagawa T; Iyakuhin Kenkyu 16 (2): 336-42 (1985)] **PEER REVIEWED** A simple, rapid method was developed for the separation and determination of polynuclear aromatic hydrocarbons (PAH) in barley malt. An ultrasonic-cyclohexane extraction method was used to separate the PAH from ground barley malt. The cyclohexane extracts were purified by chromatography through a water-deactivated silica gel-alumina column. The eluate from the column was concentrated and purified further by partitioning between dimethyl sulfoxide (DMSO) and cyclohexane. The DMSO extract was diluted with water and the PAH were extracted back into cyclohexane. The cyclohexane extract was washed with water, dried through sodium sulfate, evaporated and the resulting residue was dissolved in 80% aqueous acetonitrile:methanol (1:1) and subjected to reverse phase high performance liquid chromatography. Thirty barley malt samples were analyzed. Peaks having the same retention time as the carcinogen benzo(a)pyrene were isolated from 18 samples, and were equivalent to trace levels ranging from < 0.1-0.2 ppb. Average recoveries of 11 PAH, including benzo(a)pyrene, benzo(b)fluoranthene, indeno(1,2,3-c)pyrene, and benz(a)anthracene, added to 25 g samples at 2.5 and 5 ppb, ranged from 78-97%, with a mean relative standard deviation of 6.6%.[Joe FL et al; J Assoc Off Analyt Chem 65 (6): 1395-402 (1982)] **PEER REVIEWED** A TLC/HPLC (HIGH PRESSURE LIQUID CHROMATOGRAPHY) PROCEDURE FOR DETERMINATION OF POLYCYCLIC AROMATIC HYDROCARBONS (PAH) OCCURRING IN ASPHALT FUMES (ADSORBED ON A PARTICULAR MATTER) IS DESCRIBED. THE METHOD IS BASED ON THE EXTRACTION OF ASPHALT FUME PARTICLES, COLLECTED ON GLASS-FIBER FILTERS, USING CARBON TETRACHLORIDE. A CLEAN UP STEP IS AIDED BY A TLC PROCEDURE ON ALUMINUM TRIOXIDE THINLAYER PLATES, USING A MIXTURE OF CYCLOHEXANE/ACETONE/ETHER AS THE MOBILE PHASE. UNDER UV-LIGHT, THE PAH ARE INDICATED AS FLUORESCENT SPOTS. SEPARATION OF THE COLLECTED PAH INTO INDIVIDUAL COMPONENTS &amp; THEIR IDENTIFICATION IS PERFORMED BY THE AID OF A HPLC PROCEDURE.[RIETZ EB; ANAL LETT 12 (12): 143-54 (1979)] **PEER REVIEWED** AN INTEGRATED APPROACH COMPRISING A COMBINATION OF GLASS CAPILLARY GC, MASS SPECTROMETRY, LIQ CHROMATOGRAPHY &amp; UV SPECTROMETRY WAS USED FOR UNAMBIGUOUS IDENTIFICATION OF POLYNUCLEAR AROMATIC HYDROCARBON (PAH) IN AIRBORNE PARTICULATES. LIQUID CHROMATOGRAPHY WITH ON-LINE UV SPECTRAL SCANNING WAS VALUABLE FOR DIFFERENTIATION OF ISOMERIC &amp; COELUTING PAH. THE ADVANTAGES OF THIS APPROACH OVER GC/MS ALONE WERE ILLUSTRATED. PARENT

PAH CONTAINING 3-7 RINGS WERE FOUND IN MOST SAMPLES EXAMINED; SOME ALKYL&amp; ALKOXY-PAH WERE ALSO DETECTED. A SIMPLE, 1-STEP PROCEDURE FOR ISOLATION OF PAH BY PREPARATIVE TLC IS ALSO REPORTED. /POLYNUCLEAR AROMATIC HYDROCARBONS/[CHOUDHURY DR, BUSH B; ANAL CHEM 53 (9): 1351-6 (1981)] **PEER REVIEWED** A 4-STEP METHOD FOR THE REPRODUCIBLE ANALYSIS OF POLYNUCLEAR AROMATIC HYDROCARBONS (PAH) IN SMALL QUANTITIES OF CIGARETTE SMOKE CONDENSATE (CSC) IS PRESENTED. PAH WERE ISOLATED FROM AS LITTLE AS 1 G OF CSC BY SOLVENT PARTITION, COLUMN CHROMATOGRAPHY, &amp; ANALYSIS GEL FILTRATION (GF). THE GF ISOLATE WAS ANALYZED BY GAS CHROMATOGRAPHY. /POLYNUCLEAR AROMATIC HYDROCARBONS/[SEVERSON RF ET AL; ANAL CHEM 48 (13): 1866 (1976)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/970639?dopt=Abstract" target=new>PubMed Abstract The use of flash evaporation and pyrolysis gas chromatography-mass spectrometry as a fast screening procedure for anthropogenic substances in environmental samples is demostrated by the analysis of polluted soil and sediment samples. Polycyclic aromatic hydrocarbons, haloorganics, aliphatic hydrocarbons, heteroaromatics, elmental sulfur, cyanides, and pyrolysis product of synthetic polymers are among the anthropogenic substances that can be readily detected by this method in one analysis. Elimination of wet chemical sample preparation enables a complete analysis to be performed and data part-per-million range using mass spectrometric detection. Alternatively, detection of compounds can be achieved by all common gas chromatography detectors (flame ionization detector, electron capture detector, and flame photometric detector) and detection limits are determined by the method of detection employed.[De Leeuw JW; Anal Chem 58 (8): 1852-7 (1986)] **PEER REVIEWED** This paper describes a procedure for fractionating polynuclear aromatic compounds (PNAs) from complex matrices according to number of aromatic rings. The procedure uses cartridges packed with amino polar bonded phase backing materials to achieve chromatographic separation of polynuclear aromatic compounds. Data are provided demonstrating tha applicability of the approach for isolating PNAs from complex matrices. This procedure scheme for the isolation of PNAs. Finally, the utility of the approach is further demonstrated by applying the method to an extract of air particulate sample acquired from an oil refinery in the Lake Charles, LA (USA) area.[Karlesky DL et al; Anal Chem 58 (6): 1187-92 (1986)] **PEER REVIEWED** Nine polycyclic aromatic hydrocarbons (PHAs) contained in air samples collected on quartz fiber filters inside an urban tunnel and in a nearby mixed commerical residential area in the city of Rio de Janeiro, Brazil, were exposed to scrubbed air (to measure desorption loss) and the particle-free ambient air (to measure chemical reaction losses in the absence of desorption). The exposures were conducted for 5.5 to 9 hour periods at ambient temperature (22-26 deg C) at face velocities typical of high volume sampling. Under prevailing atmospheric conditions all nine PAHs experienced filter losses which (for most of them) followed first order kinetics. For the ambient samples, in a 6 hour exposure period, the following five PAHs showed filter losses (% in parantheses) attributed exclusively to chemical reaction: benzo(b)fluoranthene (43), benzo(k)fluoranthene (39), benzo(a)pyrene (70), benzo(ghi)perylene (44), and indeno (1,2,3-cd)pyrene (41). The other four showed the following unassigned losses: pyrene (100), fluoranthene (65), crysene (72), and benzo(a)anthracene (71). The results are discussed in the light of possible filter artifacts in PAH sampling and the use of PAH profile

signatures for source identification of atmospheric particulate matter in receptor modeling.[Miguel AH et al; Int J Environ Anal Chem 26 (3-4): 265-78 (1986)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/3771060?dopt=Abstract" target=new>PubMed Abstract AREAL Method IP-7-B. Determination of Benzo-a-Pyrene (B(a)P) and Other Polynuclear Aromatic Hydrocarbons in Indoor Air by High Performance Liquid Chromatography, indoor air, HPLC, detection limit 50 pg/cu m.[USEPA/Atmospheric Research &amp; Exposure Assessment Laboratory (AREAL); Compendium of Methods for the Determination of Air Pollutants in Indoor Air, Engineering Science, One Harrison Park, Suite 305, 401 Harrison Oaks Blvd, Cary, NC 27513 as cited in USEPA; EMMI. Environmental Monitoring Methods Index. Version 2.0 NTIS PB-95-502415 (1995)] **PEER REVIEWED** SAMPLING PROCEDURES: Measurements to determine employee exposure are best taken so that average eight-hour exposure is based on a single eight-hour sample or on two four-hour samples. Several short-time interval samples (up to 30 minutes) may also be used to determine the average exposure level. Air samples should be taken in the employee's breathing zone (air that would mostly nearly represent that inhaled by the employee). /Coal tar pitch volatiles/[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 3] **PEER REVIEWED** Glass fiber filters impregnated with (14)C-BaP were used to evaluate BaP losses under the conditions of high volume sampling. Although only losses in the order of 10% were observed for (14)C, BaP losses < or = 90% are possible during a 24 hr exposure of the filter. Irradiation studies with (14)C-BaP on dust-coated and uncoated filters indicate that the presence of particulate matter is apparently of minor importance for the stability of BaP on filters.[Seifert B, Peters J; Atmospheric Environment 14 (1): 117-9 (1980)] **PEER REVIEWED** EPA Method 610: Grab samples of water in industrial and municipal discharges must be collected in glass containers, 1 l or 1 qt amber glass, fitted with a screw cap lined with Teflon, except that the bottles must not be prerinsed with sample before collection. Fill the sample bottles, and if residual chlorine is present, add 80 mg of sodium thiosulfate per liter of sample and mix well. All samples must be iced or refrigerated from the time of collection until analysis. All samples must be extracted within 7 days of collection and completely analyzed within 40 days of extraction. Extraction is performed by adding 60 ml of methylene chloride to the sample in a separatory funnel and shaking. The combined extract is then concentrated using a Kuderna-Danish apparatus.[40 CFR 136 (7/1/86)] **PEER REVIEWED** EPA Method 625: Grab samples of water in municipal and industrial discharges must be collected in glass containers, amber, 1 l or 1 qt, fitted with a screw cap lined with Teflon, except that the bottles must not be prerinsed with sample before collection. Fill the sample bottles, and if residual chlorine is present, add 80 mg of sodium thiosulfate per liter of sample and mix well. All samples must be iced or refrigerated from the time of collection until analysis. All samples must be extracted within 7 days of collection and completely analyzed within 40 days of extraction. Extraction is performed by adding 60 ml of methylene chloride to the sample in a separatory funnel and shaking. The combined extract is

then concentrated using a Kuderna-Danish apparatus.[40 CFR 136 (7/1/86)] **PEER REVIEWED** EPA Method 1625: Collect water samples in municipal and industrial discharges in glass containers, amber, 1.1 l minimum with threaded caps lined with Teflon. Maintain samples at 0-4 deg C from the time of collection until extraction. If residual chlorine is present, add 80 mg sodium thiosulfate per liter of water. Extraction is performed by adding methylene chloride to the samples in a continuous liquid-liquid extractor and concentrated with a Kuderna-Danish apparatus. Begin sample extraction within seven days of collection, and analyze all extracts within 40 days of extraction.[40 CFR 136 (7/1/866)] **PEER REVIEWED** RCRA Method 3510: Separatory Funnel Liquid-Liquid Extraction: A measured volume of sample is serially extracted with methylene chloride. The sample is then dried and concentrated using a Kuderna-Danish apparatus. This method is applicable to the extraction and concentration of water-insoluble and slightly water-soluble organics from aqueous samples.[USEPA; Test Methods for Evaluation Solid Waste SW-846 (1986)] **PEER REVIEWED** RCRA Method 3520: Continuous Liquid-Liquid Extraction: A measured volume of sample is extracted with methylene chloride. After distillation, the sample is then dried and concentrated using a Kuderna-Danish apparatus. This method is applicable to the extraction and concentration of water-insoluble and slightly water-soluble organics from aqueous samples.[USEPA; Test Methods for Evaluation Solid Waste SW-846 (1986)] **PEER REVIEWED** RCRA Method 3540: Soxhlet Extraction: A solid sample is mixed with anhydrous sodium sulfate and extracted using an appropriate solvent in a Soxhlet extractor. The sample is then dried and concentrated using a Kuderna-Danish apparatus. This is a procedure for extracting nonvolatile and semivolatile organic compounds from solids such as soils, sludges, and waste.[USEPA; Test Methods for Evaluation Solid Waste SW-846 (1986)] **PEER REVIEWED** RCRA Method 3550: Sonication Extraction: A solid sample is mixed with anhydrous sodium sulfate to form a free-flowing powder. This is solvent extracted three times using a horn-type sonicator. The sample is then dried and concentrated using a Kuderna-Danish apparatus. This method is applicable to the extraction of nonvolatile and semivolatile organic compounds from solids such as soils, sludges, and waste.[USEPA; Test Methods for Evaluation Solid Waste SW-846 (1986)] **PEER REVIEWED** Coal tar products may be sampled by collection on a glass fiber filter with subsequent ultrasonic extraction and weighing. /Coal tar pitch volatiles/[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 1] **PEER REVIEWED** SPECIAL REFERENCES: SPECIAL REPORTS: IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Vol. 92. Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Industrial Exposures (2005). IARC Monographs provide

critical reviews of data on carcinogenicity for agents to which humans are known to be exposed and on specific exposure situations.[Summary available from, as of November 29, 2009: http://monographs.iarc.fr/ENG/Meetings/index1.php] Health &amp; Welfare Canada; Polycyclic Aromatic Hydrocarbons (1979) Report No. 80-EHD-50 Melius P; Natl Cancer Inst Monograph 65 (Use Small Fish Species Carcinog Test): 387-90 (1984). A review with twenty-two references on the metabolism of benzo(a)pyrene by fish and rat liver microsomes. U.S. Dept Health &amp; Human Services/Agency for Toxic Substances Disease Registry; Toxicological Profile for Polycyclic Aromatic Hydrocarbons (Update) (1995) NTIS# PB/95/264370 National Toxicology Program. Eleventh Report on Carcinogens (2005). The Report on Carcinogens is an informational scientific and public health document that identifies and discusses substances (including agents, mixtures, or exposure circumstances) that may pose a carcinogenic hazard to human health. Benzo(a)pyrene (50-32-8) is listed as reasonably anticipated to be a human carcinogen. /Polycyclic Aromatic Hydrocarbons/[Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s150pah.pdf] SYNONYMS AND IDENTIFIERS: RELATED HSDB RECORDS: 6299 [COAL TAR CREOSOTE] (mixture) 4031 [BENZO(E)PYRENE] (isomer) 5050 [COAL TAR] (mixture) SYNONYMS: BaP **PEER REVIEWED** Benz(a)pyrene **PEER REVIEWED** 3,4-Benz(a)pyrene **PEER REVIEWED** Benzo(d,e,f)chrysene[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley &amp; Sons, Inc. Hoboken, NJ. 2004., p. 383] **PEER REVIEWED** 3,4-Benzopirene (Italian)[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley &amp; Sons, Inc. Hoboken, NJ. 2004., p. 383] **PEER REVIEWED** 6,7-Benzopirene (Italian)[Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 2002. 4th ed.Vol 1 A-H Norwich, NY: Noyes Publications, 2002., p. 324] **PEER REVIEWED** Benzopireno (Spanish)[Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 2002. 4th ed.Vol 1 A-H Norwich, NY: Noyes Publications, 2002., p. 324] **PEER REVIEWED** 3,4-Benzopyrene[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of

Industrial Materials. 11th Edition. Wiley-Interscience, Wiley &amp; Sons, Inc. Hoboken, NJ. 2004., p. 383] **PEER REVIEWED** 6,7-Benzopyrene[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley &amp; Sons, Inc. Hoboken, NJ. 2004., p. 383] **PEER REVIEWED** Benzopyrene[Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 2002. 4th ed.Vol 1 A-H Norwich, NY: Noyes Publications, 2002., p. 324] **PEER REVIEWED** 3,4-Benzpyren (German)[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley &amp; Sons, Inc. Hoboken, NJ. 2004., p. 383] **PEER REVIEWED** 6,7-Benzpyren (German)[Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 2002. 4th ed.Vol 1 A-H Norwich, NY: Noyes Publications, 2002., p. 324] **PEER REVIEWED** 3,4-Benzypyrene[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley &amp; Sons, Inc. Hoboken, NJ. 2004., p. 383] **PEER REVIEWED** 3,4-BP[Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 2002. 4th ed.Vol 1 A-H Norwich, NY: Noyes Publications, 2002., p. 324] **PEER REVIEWED** BP **PEER REVIEWED** NSC21914[Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 2002. 4th ed.Vol 1 A-H Norwich, NY: Noyes Publications, 2002., p. 324] **PEER REVIEWED** FORMULATIONS/PREPARATIONS: A reference material of certified high purity is available[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V32 212] **PEER REVIEWED** EPA HAZARDOUS WASTE NUMBER: U022; A toxic waste when a discarded commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate. ADMINISTRATIVE INFORMATION: HAZARDOUS SUBSTANCES DATABANK NUMBER: 2554 LAST REVISION DATE: 20100603 LAST REVIEW DATE: Reviewed by SRP on 1/21/2010 UPDATE HISTORY: Complete Update on 2010-06-03, 72 fields added/edited/deleted Field Update on 2009-08-12, 2 fields added/edited/deleted

Field Update on 2009-04-16, 2 fields added/edited/deleted Field Update on 2005-09-20, 2 fields added/edited/deleted Complete Update on 2005-06-23, 2 fields added/edited/deleted Field Update on 2005-04-29, 4 fields added/edited/deleted Field Update on 2005-01-29, 2 fields added/edited/deleted Complete Update on 2003-08-29, 1 fields added/edited/deleted Complete Update on 07/22/2002, 2 fields added/edited/deleted. Complete Update on 05/31/2002, 1 field added/edited/deleted. Complete Update on 08/09/2001, 1 field added/edited/deleted. Complete Update on 09/12/2000, 1 field added/edited/deleted. Complete Update on 03/30/2000, 1 field added/edited/deleted. Complete Update on 02/11/2000, 1 field added/edited/deleted. Complete Update on 02/09/2000, 1 field added/edited/deleted. Complete Update on 09/21/1999, 1 field added/edited/deleted. Complete Update on 08/26/1999, 1 field added/edited/deleted. Complete Update on 02/01/1999, 1 field added/edited/deleted. Complete Update on 01/27/1999, 1 field added/edited/deleted. Complete Update on 11/12/1998, 1 field added/edited/deleted. Complete Update on 06/18/1998, 73 fields added/edited/deleted. Field Update on 06/02/1998, 1 field added/edited/deleted. Field Update on 02/27/1998, 1 field added/edited/deleted. Complete Update on 04/23/1997, 2 fields added/edited/deleted. Complete Update on 10/15/1996, 1 field added/edited/deleted. Complete Update on 06/19/1996, 1 field added/edited/deleted. Complete Update on 06/06/1996, 1 field added/edited/deleted. Complete Update on 05/11/1996, 1 field added/edited/deleted. Complete Update on 04/12/1996, 2 fields added/edited/deleted. Complete Update on 03/29/1996, 1 field added/edited/deleted. Complete Update on 01/24/1996, 1 field added/edited/deleted. Complete Update on 08/21/1995, 1 field added/edited/deleted.

Complete Update on 02/27/1995, 1 field added/edited/deleted. Complete Update on 01/18/1995, 1 field added/edited/deleted. Complete Update on 12/28/1994, 1 field added/edited/deleted. Complete Update on 11/08/1994, 1 field added/edited/deleted. Complete Update on 09/27/1994, 1 field added/edited/deleted. Complete Update on 06/29/1994, 1 field added/edited/deleted. Complete Update on 05/05/1994, 1 field added/edited/deleted. Complete Update on 11/01/1993, 1 field added/edited/deleted. Complete Update on 08/07/1993, 1 field added/edited/deleted. Complete Update on 04/27/1993, 1 field added/edited/deleted. Field update on 12/25/1992, 1 field added/edited/deleted. Complete Update on 11/25/1992, 1 field added/edited/deleted. Complete Update on 04/02/1992, 1 field added/edited/deleted. Complete Update on 04/01/1992, 1 field added/edited/deleted. Complete Update on 01/28/1992, 1 field added/edited/deleted. Complete Update on 07/09/1991, 1 field added/edited/deleted. Complete Update on 08/23/1990, 1 field added/edited/deleted. Complete Update on 04/16/1990, 2 fields added/edited/deleted. Complete Update on 03/06/1990, 1 field added/edited/deleted. Field update on 03/06/1990, 1 field added/edited/deleted. Complete Update on 12/19/1989, 1 field added/edited/deleted. Complete Update on 11/20/1989, 1 field added/edited/deleted. Complete Update on 10/31/1989, 93 fields added/edited/deleted. Field Update on 11/09/1988, 1 field added/edited/deleted. Complete Update on 05/31/1985 Created 19830401 by DS