Health Risks of Silica Exposure

NIOSH HAZARD REVIEW
Health Effects of Occupational

Exposure to Respirable
Crystalline Silica
DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention
National Institute for Occupational Safety and Health
April 2002
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DHHS (NIOSH) Publication No. 2002129
ii
Foreword
S ilicosis is the disease most associated with crystalline silica exposure; it is incurable but
preventable. This debilitating and often fatal lung disease persists worldwide despite
long-standing knowledge of its cause and methods for controlling it.
This Hazard Review, Health Effects of Occupational Exposure to Respirable Crystalline Silica, de-
scribes published studies and literature on the health effects of occupational exposure to respirable
crystalline silica among workers in the United States and many other countries. The review indi-
cates a significant risk of chronic silicosis for workers exposed to respirable crystalline silica over a
working lifetime at the current Occupational Safety and Health Administration (OSHA) permissi-
ble exposure limit (PEL), the Mine Safety and Health Administration (MSHA) PEL, or the Na-
tional Institute for Occupational Safety and Health (NIOSH) recommended exposure limit (REL).
In addition to the risk of silicosis, epidemiologic studies indicate that workers exposed to respirable
crystalline silica have an increased risk of developing lung cancer, pulmonary tuberculosis, and air-
ways diseases. The latest scientific information also indicates possible associations of occupational
exposure to silica dust with various other adverse health effects.
Until improved sampling and analytical methods are developed for respirable crystalline silica,
NIOSH will continue to recommend an exposure limit of 0.05 mg/m3 as a time-weighted average
(TWA) for up to a 10-hr workday during a 40-hr workweek. NIOSH also recommends substituting
less hazardous materials for crystalline silica when feasible, using appropriate respiratory protec-
tion when source controls cannot keep exposures below the REL, and making medical examina-
tions available to exposed workers.
Kathleen M. Rest, Ph.D., M.P.A.

Acting Director, National Institute for
Occupational Safety and Health
Centers for Disease Control and Prevention
iii
Abstract
O ccupational exposures to respirable crystalline silica are associated with the development of
silicosis, lung cancer, pulmonary tuberculosis, and airways diseases. These exposures may
also be related to the development of autoimmune disorders, chronic renal disease, and other
adverse health effects. Recent epidemiologic studies demonstrate that workers have a significant
risk of developing chronic silicosis when they are exposed to respirable crystalline silica over a
working lifetime at the current Occupational Safety and Health Administration (OSHA)
permissible exposure limit (PEL), the Mine Safety and Health Administration (MSHA) PEL, or the
National Institute for Occupational Safety and Health (NIOSH) recommended exposure limit
(REL).
This NIOSH Hazard Review (1) examines the health risks and diseases associated with occupa-
tional exposures to respirable crystalline silica, (2) discusses important findings of recent epide-
miologic studies, (3) provides the reader with sources of more comprehensive information about
health effects and experimental studies, (4) describes current sampling and analytical methods and
their limitations for assessing occupational exposures to respirable crystalline silica, and (5) sug-
gests many areas for further research.
Current sampling and analytical methods used to evaluate occupational exposure to respirable crys-
talline silica do not meet the accuracy criterion needed to quantify exposures at concentrations be-
low the NIOSH REL of 0.05 mg/m3 as a time-weighted average (TWA) for up to a 10-hr workday
during a 40-hr workweek. Until improved sampling and analytical methods are developed for respi-
rable crystalline silica, NIOSH will continue to recommend an exposure limit of 0.05 mg/m3 to re-
duce the risk of developing silicosis, lung cancer, and other adverse health effects. NIOSH also
recommends minimizing the risk of illness that remains for workers exposed at the REL by substi-
tuting less hazardous materials for crystalline silica when feasible, by using appropriate respiratory
protection when source controls cannot keep exposures below the NIOSH REL, and by making
medical examinations available to exposed workers.
iv
Executive Summary
O ccupational exposures to respirable
crystalline silica occur in a variety of
industries and occupations because of its
al. 1998]. Over a 40- or 45-year working life-
time, workers have a significant chance (at
least 1 in 100) of developing radiographic
extremely common natural occurrence and silicosis when exposed to respirable crystal-
the wide uses of materials and products that line silica at the Occupational Safety and
contain it. At least 1.7 million U.S. workers Health Administration (OSHA) permissible
are potentially exposed to respirable crystal- exposure limit (PEL), the Mine Safety and
line silica [NIOSH 1991], and many are Health Administration (MSHA) PEL, or the Na-
exposed to concentrations that exceed limits tional Institute for Occupational Safety and
defined by current regulations and standards. Health (NIOSH) recommended exposure limit
(REL).*
Silicosis, usually a nodular pulmonary fibrosis,
is the disease most associated with exposure to Silicosis may be complicated by severe myco-
respirable crystalline silica. Although the re- bacterial or fungal infections. About half of
ported mortality associated with silicosis has these are caused by Mycobacterium tuberculo-
declined over the past several decades, many sis and result in TB. Epidemiologic studies
silicosis-associated deaths still occur (nearly have firmly established that silicosis is a risk
300 deaths were reported each year during the factor for developing TB.
period 19921995) [NIOSH 1996a; Althouse
1998]. In addition, the number of silicosis- The carcinogenicity of crystalline silica in hu-
associated deaths among persons aged 15 to 44 mans has been strongly debated in the scien-
has not declined substantially [CDC 1998a,b]. tific community. In 1996, the International
An unknown number of workers also continue Agency for Research on Cancer (IARC) re-
to die from silica-related diseases such as pul- viewed the published experimental and epide-
monary tuberculosis (TB), lung cancer, and miologic studies of cancer in animals and
scleroderma. The number of cases of silicosis workers exposed to respirable crystalline sil-
and silica-related diseases in the United States ica and concluded that there was sufficient
today is unknown. evidence in humans for the carcinogenicity of
inhaled crystalline silica in the form of quartz
or cristobalite from occupational sources
Symptoms of acute silicosis, another form of
[IARC 1997]. In the same year, directors of the
silicosis, may develop shortly after exposure to
American Thoracic Society (ATS) adopted an
high concentrations of respirable crystalline
official statement that described the adverse
silica. Epidemiologic studies focus on chronic
health effects of exposure to crystalline silica,
silicosis, which develops years after exposure
including lung cancer [ATS 1997]. The ATS
to relatively low concentrations of respirable
found that the available data support the con-
crystalline silica. Epidemiologic studies have
clusion that silicosis produces increased risk
found that chronic silicosis may develop or
progress even after occupational exposure has
*See appendix for the OSHA and MSHA PELs. The
ceased [Hessel et al. 1988; Hnizdo and NIOSH REL is 0.05 mg/m3 as a time-weighted aver-
Sluis-Cremer 1993; Hnizdo and Murray 1998; age (TWA) for up to a 10-hr workday during a 40-hr
Ng et al. 1987; Kreiss and Zhen 1996; Miller et workweek.
v
for bronchogenic carcinoma. However, the frequent or absent in nonsmokers. Exposure to
ATS noted that less information was available respirable crystalline silica is not associated
for lung cancer risks among silicotics who had with asthma.
never smoked and for silica-exposed work-
ers who did not have silicosis. They also stated Significant increases in mortality from nonma-
that it was less clear whether silica exposure lignant respiratory disease (a broad category that
was associated with lung cancer in the absence can include silicosis and other pneumoconioses,
of silicosis. NIOSH has reviewed the studies chronic bronchitis, emphysema, asthma, and
considered by IARC and ATS, and NIOSH other related respiratory conditions) have been
concurs with the conclusions of IARC [1997] reported for silica-exposed workers [Checkoway
and the ATS [1997]. These conclusions agree et al. 1997, 1993; Chen et al. 1992; Cherry et al.
with NIOSH testimony to OSHA, in which 1998; Brown et al. 1986; Costello and Graham
NIOSH recommended that crystalline silica be 1988; Costello et al. 1995; Costello 1983;
considered a potential occupational carcinogen Steenland and Brown 1995b; Steenland and
[54 Fed. Reg.* 2521 (1989)]. Further research Beaumont 1986; Thomas and Stewart 1987;
is needed to determine the exposure-response Thomas 1990] and silicotics [Goldsmith et al.
relationship between lung cancer in nonsmok- 1995; Brown et al. 1997; Rosenman et al. 1995].
ers and occupational silica dust exposure and
to determine why lung cancer risks appear to Many case reports have been published about
be higher in workers with silicosis. The cellu- autoimmune diseases or autoimmune-related
lar mechanisms for development of lung can- diseases in workers exposed to crystalline sil-
cer after crystalline silica exposure have been ica or workers with silicosis. In addition, sev-
explored in many experimental studies and are eral recent epidemiologic studies reported
not yet fully understood. statistically significant numbers of excess
cases or deaths from known autoimmune dis-
Statistically significant excesses of mortality eases or immunologic disorders (scleroderma,
from stomach or gastric cancer have been systemic lupus erythematosus, rheumatoid ar-
reported in various occupational groups ex- thritis, sarcoidosis), chronic renal disease, and
posed to crystalline silica. However, no con- subclinical renal changes. The pathogenesis
clusion about an association has been reached of autoimmune and renal diseases in silica-
because most studies did not adjust for the ef- exposed workers is not clear.
fects of confounding factors or assess an
exposure-response relationship for crystalline Various other health effects (such as hepatic or
silica. The same problem exists for the infre- hepatosplenic silicosis, extrapulmonary depo-
quent reports of statistically significant num- sition of silica particles, liver granulomas,
bers of excess deaths or cases of other nonlung hepatic porphyria, cutaneous silica granulo-
cancers in silica-exposed workers. mas, pulmonary alveolar proteinosis, podoco-
niosis, and dental abrasion) have been reported
Occupational exposure to respirable crystalline in studies of silica-exposed workers, but these
silica is associated with chronic obstructive pul- effects have not been studied in depth with
monary disease, including bronchitis and em- epidemiologic methods.
physema. The results of some epidemiologic
studies suggest that these diseases may be less This Hazard Review also provides an abbrevi-
ated review of experimental research studies
conducted to identify the molecular mecha-
*Federal Register. See Fed. Reg. in references. nisms responsible for the development of
vi
silicosis and lung cancer. The results of these the importance of using appropriate control
studies indicate the need for (1) additional technologies and other protective measures, and
long-term carcinogenesis studies in animals to (3) exposure sampling and analytical methods
determine dose-response relationships and that will allow quantification of crystalline sil-
(2) in vivo and in vitro studies to develop effec- ica at low airborne concentrations (currently
tive cellular and molecular models of carcino- these techniques do not meet the accuracy crite-
genesis. rion needed to quantify exposures at concentra-
tions below the NIOSH REL).
Although a large body of published literature
describes the health effects of crystalline sil-
ica, some areas require further research. Many Until improved sampling and analytical meth-
uncertainties exist, including (1) mechanisms ods are developed for respirable crystalline sil-
and the influence of particle characteristics on ica, NIOSH will continue to recommend an
development of disease; (2) toxicity and patho- exposure limit of 0.05 mg/m3 to reduce the risk
genicity of nonquartz crystalline silica, silica of developing silicosis, lung cancer, and other
substitutes, and dust mixtures; (3) transloca- adverse health effects. NIOSH also recom-
tion of particles from the lung; and (4) dose/ mends minimizing the risk of illness that re-
exposure-response relationships in animals mains for workers exposed at the REL by
and in humans. In addition, further information substituting less hazardous materials for crys-
is needed about (1) methods for reducing dust talline silica when feasible, by using appropri-
exposures in a wide variety of industries and ate respiratory protection when source controls
the feasibility of implementing such methods, cannot keep exposures below the NIOSH REL,
(2) methods for effectively communicating to and by making medical examinations available
workers the dangers of inhaling silica dust and to exposed workers.
vii
viii
Contents
Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iii
Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iv
Executive Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v
Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi
Glossary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xv
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xvii
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1 Definition of Crystalline Silica . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.2 Current Health Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.3 History of NIOSH Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.4 Purpose and Scope . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2 Properties, Production, and Potential for Exposure . . . . . . 4

2.1 Chemical and Physical Properties. . . . . . . . . . . . . . . . . . . . . . . . . 4
2.2 Number of Workers Potentially Exposed . . . . . . . . . . . . . . . . . . . . . 4
2.3 Dust-Generating Activities, Uses, and Potential Exposures. . . . . . . . . . . . 4
2.4 Sampling and Analytical Methods . . . . . . . . . . . . . . . . . . . . . . . . 6
2.4.1 Sampling Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

2.4.2 Analytical Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
2.4.3 Feasibility of Measuring Crystalline Silica
at Various Concentrations . . . . . . . . . . . . . . . . . . . . . . . . . 17
3 Human Health Effects . . . . . . . . . . . . . . . . . . . . 21

3.1 Epidemiologic Considerations in Occupational Respiratory Disease Studies. . . 21
3.1.1 Study Designs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
3.1.2 Sources of Bias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
3.2 Silicosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
3.2.1 Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
3.2.2 Epidemiologic Exposure-Response Models of Silicosis . . . . . . . . . . 24
3.3 TB and Other Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

3.3.1 Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
3.3.2 Epidemiologic Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
ix
3.4 Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
3.4.1 Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
3.4.2 Epidemiologic Studies of Lung Cancer . . . . . . . . . . . . . . . . . . 38
3.4.3 Other Cancers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
3.5 Other Nonmalignant Respiratory Diseases and Related Conditions . . . . . . . 51
3.5.1 COPD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
3.5.2 Asthma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
3.5.3 Chronic Bronchitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
3.5.4 Abnormalities in Pulmonary Function Tests . . . . . . . . . . . . . . . . 59
3.5.5 Emphysema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
3.5.6 Nonmalignant Respiratory Disease (NMRD) Mortality . . . . . . . . . . 62
3.6 Autoimmune and Chronic Renal Diseases . . . . . . . . . . . . . . . . . . . . 67

3.7 Other Health Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
4 Experimental Studies. . . . . . . . . . . . . . . . . . . . . 80
4.1 Biomarkers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
4.2 Cytotoxicity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
4.3 Genotoxicity and Related Effects . . . . . . . . . . . . . . . . . . . . . . . . . 89
4.4 Carcinogenicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
5 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . 96
5.1 Lung Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
5.2 Noncarcinogenic Health Effects . . . . . . . . . . . . . . . . . . . . . . . . . 96
5.3 Exposures, Monitoring, and Controls . . . . . . . . . . . . . . . . . . . . . . . 97
6 Research Needs . . . . . . . . . . . . . . . . . . . . . . . 99
6.1 Health-Related Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
6.2 Research Related to Exposure Measurement . . . . . . . . . . . . . . . . . . . 100
6.3 Research Related to the Control of Exposure . . . . . . . . . . . . . . . . . . . 101
References . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
Appendix. Occupational Exposure Limits . . . . . . . . . . . . 127
x
Abbreviations
ACGIH American Conference of Governmental Industrial Hygienists
AMG alpha-1-microglobulin
ATS American Thoracic Society
BAL bronchoalveolar lavage
BMG beta-1-microglobulin
BMI body mass index
EC degree(s) Celsius
CA chromosomal aberration(s)
cc cubic centimeter
CDC Centers for Disease Control and Prevention
CEN European Standardization Committee
CFR Code of Federal Regulations
CI confidence interval
cm centimeter(s)
COC census occupation code
COPD chronic obstructive pulmonary disease
Cu copper
CV coefficient of variation
CV pooled coefficient of variation
CWP coal workers pneumoconiosis
DE diatomaceous earth
DLCO diffusing capacity of the lung for carbon monoxide
DNA deoxyribonucleic acid
EPA U.S. Environmental Protection Agency
EF degree(s) Fahrenheit
FEV1 forced expiratory volume in 1 second
FVC forced vital capacity
xi
g gram(s)
HIV human immunodeficiency virus
HLA human leukocyte antigen
hprt hypoxanthine-guanine phosphoribosyl transferase
hr hour(s)
HSE Health and Safety Executive (United Kingdom)
HVLV high-velocity/low-volume
IARC International Agency for Research on Cancer
ICD9 International Classification of Diseases, 9th edition
Ig immunoglobulin
IGLV immunoglobulin lambda-variable chain
ILO International Labour Organization
IR infrared absorption
ISO International Organization for Standardization
K" electron ionization energy
KBr potassium bromide
kv kilovolt(s)
L liter(s)
LOD limit of detection
m meter(s)
mA milliamp(s)
MDHS Methods for the Determination of Hazardous Substances
(Health and Safety Executive, United Kingdom)
mg milligram(s)
mg/m3 @ yr milligrams per cubic meter times years
min minute(s)
ml milliliter(s)
mm millimeter(s)
mppcf million particles per cubic foot
MSHA Mine Safety and Health Administration
NAG beta-N-acetyl-D-glucosaminidase
xii
NIOSH National Institute for Occupational Safety and Health
NIST National Institute of Standards and Technology
NMRD nonmalignant respiratory disease
NOES National Occupational Exposure Survey
NOHSM National Occupational Health Survey of Mining
NOMS U.S. National Occupational Mortality Surveillance
NTM nontuberculous mycobacteria
OR odds ratio
OSHA Occupational Safety and Health Administration
P probability
PAP pulmonary alveolar proteinosis
PAT proficiency analytical testing
PDGF platelet-derived growth factor
PEL permissible exposure limit
PMR proportionate mortality ratio
ppm parts per million
PVC polyvinyl chloride
RDS respirable dust standard
REL recommended exposure limit
RF radio frequency
RFLP restriction fragment length polymorphism
ROS reactive oxygen species
RSD relative standard deviation
RSD pooled relative standard deviation
SCE sister chromatid exchange
SCG single cell gel/comet
SIC standard industrial classification
SiO2 silicon dioxide
SIR standardized incidence ratio
SMR standardized mortality ratio
xiii
SRR standardized rate ratio
TGF transforming growth factor
TB pulmonary tuberculosis
THF tetrahydrofuran
TWA time-weighted average
U.K. United Kingdom
U.S. United States
VC vital capacity
WASP Workplace Analysis Scheme for Proficiency
WHO World Health Organization
wk week(s)
XRD X-ray diffraction
yr year(s)
g microgram(s)
m micrometer(s)
% percent
xiv
Glossary
Aerodynamic diameter: The diameter of a sphere with a density of 1 g/cm3 and with the same ve-
locity (due to gravity) as the particle of interest [EPA 1996]. Particles of a given aerodynamic diam-
eter move within the air spaces of the respiratory system identically, regardless of density or shape
[NIOSH 1995a].
Chronic obstructive pulmonary disease (COPD): Includes airways diseases such as asthma,
chronic bronchitis, and emphysema and is characterized by airways dysfunction [Becklake 1992].
Clearance: The translocation and removal of deposited particles from the respiratory tract.
Concentration: The amount of a substance (e.g., dust particles) contained per unit volume of air.
Confidence interval (CI), confidence limits: A range of values (determined by the degree of pre-
sumed random variability in the data) within which the value of a parameter (e.g., a mean or relative
risk) is believed to lie with the specified level of confidence. The boundaries of a confidence inter-
val are the confidence limits [Last 1988]. These include the lower confidence limit and the upper
confidence limit.
Crystalline silica (or free silica): Silicon dioxide (SiO2). Crystalline refers to the orientation of
SiO2 molecules in a fixed pattern as opposed to a nonperiodic, random molecular arrangement de-
fined as amorphous. The three most common crystalline forms of silica encountered in the work-
place environment are quartz, tridymite, and cristobalite [NIOSH 1974].
ILO category: The determination of profusion of small opacities observed by reading chest radio-
graphs according to classification of pneumoconioses guidelines developed by the International
Labour Organization (ILO). The latest classification guidelines were published by the International
Labour Office in 1980 [ILO 1980].
Incidence: The frequency with which new cases of a disease occur in a given time period.
Incidence rate: The rate at which new events occur in a population. The number of new events
(e.g., new cases of a disease diagnosed or reported during a defined period) is divided by the num-
ber of persons in the population in which the cases occurred [Last 1988].
Inhalable dust: The particulate mass fraction of dust in the work environment that can be inhaled
and deposited anywhere in the respiratory tract.
Nontuberculous mycobacteria: Mycobacteria species other than the Mycobacterium tuberculosis

complex (e.g., Mycobacterium avium complex).
xv
Prevalence: The number of disease cases in a specific population at a particular time [Last 1988].
Prevalence rate (ratio): The total number of all individuals with an attribute or disease at a given
time or during a given period divided by the population at risk of having the attribute or disease at
this point in time or midway through the period [Last 1988].
Proportionate mortality ratio (PMR): Ratio of the proportion of deaths from a specific cause in an
exposed population compared with the corresponding ratio in the nonexposed population. For ex-
ample, the proportion of deaths from disease X in the exposed population could be compared with
the proportion of deaths from disease X in the nonexposed population [NIOSH 2000].
Quartz: Crystalline silicon dioxide (SiO2) not chemically combined with other substances and hav-
ing a distinctive physical structure.
Respirable crystalline silica: That portion of airborne crystalline silica that is capable of entering
the gas-exchange regions of the lungs if inhaled; by convention, a particle-size-selective fraction
of the total airborne dust; includes particles with aerodynamic diameters less than approximately
10 m and has a 50% deposition efficiency for particles with an aerodynamic diameter of approxi-
mately 4 m.
Sarcoidosis: A rare multisystem granulomatous disease characterized by alterations in the immune

system [Fanburg 1992].
Scleroderma (progressive systemic sclerosis): A rare multisystem disorder characterized by in-

flammatory, vascular, and fibrotic changes usually involving the skin, blood vessels, joints, and
skeletal muscle [Archer and Gordon 1996].
Standardized mortality ratio: The ratio of the number of deaths observed in the study population to
the number of deaths expected if the study population had the same rate structure as the standard
population [Last 1988].
Standardized rate ratio: A rate ratio in which the numerator and denominator rates have been stan-
dardized to the same (standard) population distribution [Last 1988].
xvi
Acknowledgments
T his Hazard Review was developed by the staff of the National Institute for Occupational Safety
and Health (NIOSH). Paul A. Schulte, Director, Education and Information Division (EID),
had overall responsibility for the document. Faye L. Rice (EID) was the principal author. The
analytical methods section was prepared by Rosa Key-Schwartz, Ph.D.; David Bartley, Ph.D; Paul
Baron, Ph.D; and Paul Schlecht. Michael Gressel and Alan Echt contributed material on control
technology.
The following NIOSH staff provided critical review and comments on this document and previous
versions: Martin Abell; Heinz W. Ahlers, J.D.; Rochelle Althouse; Harlan Amandus, Ph.D.;
Michael Attfield, Ph.D.; Nancy Bollinger, Ph.D.; Lorraine Cameron, Ph.D.; Robert Castellan,
M.D.; Joseph Cocalis; Joseph Costello; Clayton Doak; Jerome Flesch; Bryan Hardin, Ph.D.; Kent
Hatfield, Ph.D.; Frank Hearl; Paul Hewett, Ph.D.; Eva Hnizdo, Ph.D. (formerly of the National
Centre for Occupational Health, South Africa); Michael Jacobsen, Ph.D. (visiting scientist);
Kathleen Kreiss, M.D.; Kenneth Linch; Charles Lorberau; Tong-man Ong, Ph.D.; John Parker,
M.D.; Larry Reed; Karl Sieber, Ph.D.; Rosemary Sokas, M.D.; Leslie Stayner, Ph.D.; Kyle
Steenland, Ph.D.; Patricia Sullivan, Sc.D.; Marie Haring Sweeney, Ph.D.; Gregory Wagner,
M.D.; William Wallace, Ph.D.; Joann Wess; Ralph Zumwalde.
Editorial review and camera-copy production were provided by Vanessa L. Becks, Susan E.
Feldmann, Joyce D. Godfrey, Anne C. Hamilton, Susan R. Kaelin, Laura A. Stroup, Kristina M.
Wasmund, and Jane B. Weber. Dale Camper and Ronald Schuler performed literature searches, and
the EID Library staff collected literature used in the development of the document.
NIOSH also appreciates the comments of the following external reviewers:
William Beckett, M.D., M.P.H. Jeffrey Gift, Ph.D.

University of Rochester School Senior Health Scientist
of Medicine U.S. Environmental Protection Agency
P.O. Box EHSC NCEA-RTP Maildrop 52
575 Elmwood Avenue Research Triangle Park, NC 27711
Rochester, NY 14642
David Goldsmith, Ph.D.
Harvey Checkoway, Ph.D. Department of Environmental and
Department of Environmental Health Occupational Health
University of Washington George Washington University
Box 357234 2300 K Street, N.W., Suite 201
Seattle, WA 981957234 Washington, DC 20037
Gerald S. Davis, M.D. Eva Hnizdo, Ph.D.

University of Vermont College of Medicine Epidemiology and Surveillance Section
Pulmonary Unit National Centre for Occupational Health
Given C317 P.O. Box 4788
Burlington, VT 05405 Johannesburg 2000, South Africa
xvii
Janet Hughes, Ph.D. Loretta Schuman, Ph.D.
Department of Biostatistics Directorate of Health Standards Program
and Epidemiology Occupational Safety and Health
Tulane School of Public Health Administration
and Tropical Medicine 200 Constitution Avenue, N.W., Room N3718
1430 Tulane Avenue Washington, DC 20210
New Orleans, LA 70112
James Sharpe
Carol Jones, Ph.D. Director of Safety and Health Services
Senior Health Specialist National Stone Association
Mine Safety and Health Administration 1415 Elliot Place, N.W.
4015 Wilson Boulevard, Room 622 Washington, DC 200072599
Arlington, VA 22203
David M. Tucker
William Kojola Manager, Industrial Hygiene
American Federation of Labor and Norfolk Southern Corporation
Congress of Industrial Organizations Environmental Protection
Department of Occupational Safety and Health 110 Franklin Road, S.E.
815 Sixteenth Street, N.W. Box 13
Washington, DC 20006 Roanoke, VA 240420013
Allen G. Macneski John A. Ulizio

Manager, Environmental Safety and Health Vice President
Bechtel National, Inc. U.S. Silica Company
151 Lafayette Drive P.O. Box 187
Oak Ridge, TN 37830 Berkeley Springs, WV 25411
Michelle Schaper, Ph.D. James L. Weeks, Sc.D.

Toxicologist George Washington University Medical Center
Directorate of Technical Support Division of Occupational and
Mine Safety and Health Administration Environmental Medicine
4015 Wilson Boulevard, Room 622 2300 K Street, N.W., Suite 201
Arlington, VA 22203 Washington, DC 20037
References and information were submitted by William G.B. Graham, M.D., University of Ver-
mont, College of Medicine. The author especially thanks David Goldsmith, Ph.D., for his major
contribution and efforts on a previous draft.
xviii
1 Introduction
1.1 Definition of Crystalline 1.2 Current Health Issues
Silica
Occupational exposure to respirable crystal-
line silica is a serious but preventable health
Silica refers to the chemical compound silicon hazard. Since 1968, reported mortality associ-
dioxide (SiO2), which occurs in a crystalline or ated with silicosis has declined; however, 200
noncrystalline (amorphous) form. Crystalline to 300 such deaths were reported each year
silica may be found in more than one form during the period 19921995 [NIOSH 1996a;
(polymorphism). The polymorphic forms of Althouse 1998]. Furthermore, the number of
crystalline silica are alpha quartz, beta quartz, silicosis-related deaths among persons aged
tridymite, cristobalite, keatite, coesite, stisho- 15 to 44 did not decline substantially during
vite, and moganite [Ampian and Virta 1992; 19681994, accounting for 207 of the
Heaney 1994; Guthrie and Heaney 1995]. Each 14,824 silicosis-related deaths during this
polymorph is unique in its spacing, lattice struc- period [CDC 1998a,b]. In addition, an un-
ture, and angular relationship of the atoms. In known number of unreported or undiagnosed
nature, the alpha (or low) form of quartz is the worker deaths occur each year from silicosis
most common [Virta 1993]. This form is so and other silica-related diseases such as pul-
abundant that the term quartz is often used in monary tuberculosis (TB), lung cancer, and
place of the general term crystalline silica scleroderma. The number of current cases of
[BOM 1992; Virta 1993]. Quartz is a common silicosis and silica-related disease in the United
component of soil and rocks; consequently, States is also unknown.
workers are potentially exposed to quartz
dust in many occupations and industries (see Prevention and elimination of silicosis and
Section 2.3). Cristobalite and tridymite are silica-related disease in the United States are
found in rocks and soil and are produced in priorities of the National Institute for Occu-
some industrial operations when alpha quartz or pational Safety and Health (NIOSH), the Oc-
amorphous silica is heated (such as foundry pro- cupational Safety and Health Administra-
cesses, calcining of diatomaceous earth, brick tion (OSHA), the Mine Safety and Health
and ceramics manufacturing, and silicon car- Administration (MSHA), and the American
bide production) [NIOSH 1974; Weill et al. Lung Association [DOL 1996]. International
1994; Virta 1993; Altieri et al. 1984]. Burning of health agencies have also expressed concern
agricultural waste or products such as rice hulls about the continuing occurrence of silicosis
may also cause amorphous silica to become and silica-related diseases. The International
cristobalite (a crystalline form) [Rabovsky 1995; Agency for Research on Cancer (IARC) re-
IARC 1997]. The other polymorphs (i.e., keatite, cently reviewed the results of post-1986
coesite, stishovite, and moganite) are rarely or epidemiologic studies of lung cancer and occu-
never observed in nature [Ampian and Virta pational exposure to crystalline silica. They
1992]. concluded that there is sufficient evidence in
1
1 INTRODUCTION
humans for the carcinogenicity of inhaled 1979 to 1991 reported that TB comortality was
crystalline silica in the form of quartz or at least several times higher in decedents with
cristobalite from occupational sources (i.e., silicosis than in decedents with asbestosis,
IARC category Group 1 carcinogen) [IARC with coal workers pneumoconiosis (CWP),
1997]. In 1991, the International Labour Office or without silicosis, asbestosis, or CWP
published a document describing methods for [Althouse et al. 1995]. The U.S. Centers for
preventing and controlling occupational lung Disease Control and Prevention (CDC), WHO,
diseases, including silicosis [ILO 1991]. And and the American Thoracic Society (ATS) have
in 1993, the Office of Occupational Health of recently published information about risk fac-
the World Health Organization (WHO) called tors for TB, including occupational exposure
for increased medical surveillance of mineral- to respirable crystalline silica [CDC 1995;
dust-exposed workers to prevent pneumo- WHO 1996; ATS 1997]. The U.S. Environ-
conioses such as silicosis and asbestosis [WHO mental Protection Agency (EPA) suggested
1993]. Epidemiologic studies published after further investigation of the health effects of
the IARC review [IARC 1997] provide addi- ambient crystalline silica exposures in poten-
tional evidence for an exposure-response rela- tially sensitive subgroups, including infants
tionship of respirable crystalline silica with lung and persons with a respiratory infection or dis-
cancer mortality or morbidity (see Section ease such as TB or pneumonia [EPA 1996].
3.4.2.1).
Recent epidemiologic studies of occupational
Several recent epidemiologic studies indicate exposure to crystalline silica dust have also re-
that current occupational standards are not suf- ported increased incidence ofor mortality
ficiently protective to prevent the occurrence fromextrapulmonary diseases such as sclero-
of chronic silicosis. Epidemiologic studies of derma, rheumatoid arthritis, other autoimmune
workers in the United States [Kreiss and Zhen disorders, and renal disease [ATS 1997].
1996; Steenland and Brown 1995a; Rosenman
et al. 1996; Hughes et al. 1998], Canada [Muir
Experimental research has shown that crystal-
et al. 1989a,b; Muir 1991], Hong Kong [Ng
line silica is not an inert dust. The toxicity of
and Chan 1994], and South Africa [Hnizdo and
crystalline silica particles is related to reactive
Sluis-Cremer 1993] have reported significant
sites on the surfaces of silica particles. Further
risks of silicosis over a working lifetime at
discussion of in vitro studies of the biologic
concentrations of quartz or respirable dust con-
activity and factors that modify toxicity are
taining quartz that are below the current
found in Section 3.2.1 and Section 4.
NIOSH recommended exposure limit (REL)
[NIOSH 1974], OSHA permissible exposure
limit (PEL) [29 CFR*1910.1000], and the
1.3 History of NIOSH Activity
MSHA PEL [30 CFR 56, 57, 70, 71] (see Ap-
pendix and Table 12 in Chapter 3). In 1974, NIOSH reviewed the available health
effects data on occupational exposure to respi-
TB is an infectious disease that poses a threat rable crystalline silica and determined that the
to the health of silica-exposed workers and principal adverse health effect was silicosis
the public. A survey of U.S. mortality data for [NIOSH 1974]. At that time, NIOSH recom-
mended that occupational exposure to respira-
ble crystalline silica dust be controlled so that
workers would not be exposed to the airborne
*
Code of Federal Regulations. See CFR in references. particulate at a time-weighted average (TWA)
2 Respirable Crystalline Silica

1 INTRODUCTION
concentration greater than 50 micrograms per from silicosis and cancer [54 Fed. Reg.* 2521
cubic meter of air (50 g/m3or 0.05 mg/m3), (1989)]. In addition, NIOSH testimony re-
determined during a full-shift sample for up to ferred to the IARC [1987] review and recom-
a 10-hr workday during a 40-hr workweek. A mended that OSHA label crystalline silica a
later NIOSH report (Review of the Literature potential occupational carcinogen [54 Fed.
on Crystalline Silica) concluded that addi- Reg. 2521 (1989)].
tional toxicologic and epidemiologic studies
were needed to determine (1) the relationship
between respirable crystalline silica dose and 1.4 Purpose and Scope
the risk of developing silicosis and lung cancer
and (2) the adverse effects of crystalline silica The numerous health effects of occupational
on the kidney [NIOSH 1983a]. Since then, ad- exposure to respirable crystalline silica are re-
ditional studies reported an increased inci- viewed in the chapters of several recent books
dence of malignant tumors in the lungs of rats [Graham 1998; Davis 1996; Green and
exposed to either inhalation or intratracheal Vallyathan 1996; McDonald 1996; Seaton 1995;
administration of various forms and prepara- Morgan and Reger 1995; Elmes 1994; Gold-
tions of respirable crystalline silica [Holland smith 1994a,b; Weill et al. 1994; Wagner 1994].
et al. 1986; Dagle et al. 1986; Groth et al. This NIOSH Hazard Review summarizes the
1986; Muhle et al. 1989; Spiethoff et al. health effects of occupational exposure to respi-
1992]. On the basis of the evidence from the rable crystalline silica reported in literature pub-
animal studies published by 1986, IARC con- lished through March 1999. The review empha-
cluded that sufficient evidence existed for sizes recent important epidemiologic studies of
the carcinogenicity of respirable crystalline sil- occupational exposure to respirable crystalline
ica in experimental animals but only limited silica with regard to (1) the quantitative risk of
evidence existed for carcinogenicity in hu- chronic silicosis, (2) lung cancer, (3) autoim-
mans [IARC 1987]. During the 1988 OSHA mune disease, (4) chronic renal disease, and
rulemaking activity on air contaminants, (5) chronic obstructive pulmonary disease. In
NIOSH recommended an exposure limit of addition, the review describes limitations of the
0.05 mg/m3 as respirable free silica for all current sampling and analytical methods for
crystalline forms of silica to protect workers quantifying occupational exposures to silica.
*
Federal Register. See Fed. Reg. in references.
Respirable Crystalline Silica 3

2 Properties, Production, and
Potential for Exposure
2.1 Chemical and Physical portion of dust to liquid; and the presence of
Properties trace minerals [King and McGeorge 1938;
King 1937; Iler 1979; Wiecek 1988; IARC
In the crystalline state, one silicon atom and 1997; Guthrie 1997]. However, the dissolution
four oxygen atoms are arranged in an ordered, of quartz does not contribute substantially to
repetitive array of three-dimensional tetrahe- its clearance or to changes in its biological ac-
drons. The silicon atom is the center of the tet- tivity [IARC 1997; Heppleston 1984; Vigliani
rahedron. Each of the four corners consists of a and Pernis 1958].
shared oxygen atom.
2.2 Number of Workers
Exposure to changes in temperature and pres- Potentially Exposed
sure, either natural or synthetic, may cause the
crystalline structure to change [Iler 1979; NIOSH [1991] estimates that at least 1.7 mil-
Klein and Hurlbut 1993; Navrotsky 1994; lion U.S. workers are potentially exposed to
Hemley et al. 1994; IARC 1997]. An example respirable crystalline silica. This estimate is
of a naturally occurring pressure change is the based on information from the National Occu-
transformation of alpha quartz to coesite in a pational Exposure Survey (NOES) [NIOSH
rock subjected to the impact of a large meteor- 1983b] and the County Business Patterns 1986
ite [Iler 1979; Klein and Hurlbut 1993; IARC [Bureau of the Census 1986]. Table 1 lists the
1997]. Alpha quartz and beta quartz are the re- nonmining industries (excluding agriculture)
spective designations given to the low- and and mining industries with the largest numbers
high-temperature crystal structures. Quartz of workers potentially exposed to respirable
changes from the alpha to the beta form at crystalline silica. In addition, an undetermined
573 C (1,063 F) [Ampian and Virta 1992; portion of the 3.7 million U.S. agricultural work-
NIOSH 1983a; Virta 1993; Guthrie and ers [Bureau of the Census 1997] may be exposed
Heaney 1995]. to dust containing a significant percentage of re-
spirable crystalline silica [Linch et al. 1998].
The solubility of quartz in water at room tem-
perature ranges from 6 to 11 micrograms per 2.3 Dust-Generating Activities,
cubic centimeter (g/cm3) (6 to 11 parts per Uses, and Potential
million [ppm]) as SiO2 [Coyle 1982; Iler Exposures
1979]. Quartz is slightly soluble in body fluids,
where it forms silicic acid and is excreted by Crystalline silica (quartz) is a component of
the urinary system [IARC 1987]. The amount nearly every mineral deposit [Greskevitch et al.
of silica dissolved depends on various factors, 1992]. Thus most crystalline silica exposures
including particle size, shape, and structure; are to mixed dust with variable silica content
solution temperature; viscosity; pH; the pro- that must be measured by dust collection and

Table 1. Nonmining and mining industries with the largest numbers of U.S. workers potentially
exposed to respirable crystalline silica, 1986
Estimated number of % total

worke rs po tentia lly workers exposed
SIC * Industry exposed (1986) (NOES)
Nonm ining
industries:
174 Maso nry, stonework, tile setting, and plastering 131,986 32.7
734 Services to dwellings and other buildings 65,812 10.3
327 Concrete, gypsum , and p laster products 63,456 33.3
176 Roofing and sheet metal work 51,153 25.3
356 General industrial machinery and equipment 44,991 16.2
807 Medical and dental laboratories 37,063 30.0
493 Combination of gas and electric and other utilities 35,074 21.2
179 Miscellaneous special trade contractors 32,615 7.8
753 Automotive repair shops 30,826 7.1
326 Pottery and related products 29,772 81.7
Mining
industries:
13 Oil and gas extraction 408,175 100
12 Bituminous coal and lignite mining 174,131 100
14 Mining and qua rrying of nonme tallic minerals,

except fuels 100,546 100
10 Metal mining 39,856 100
Source: NIOSH [1991].

*
Standard industrial classification.
Estimated number of workers potentially exposed to the hazards of flint, quartz, sand, or silica powder; based on data from the
County Business Patterns 1986 [Bureau of the Census 1986] and the National Occupational Exposure Survey (NOES)
[NIOSH 1983b]. For SICs in which the estimates differed for individual hazards, the highest percentage was used for that SIC.
Exposure is assumed to be 100% in the mining industries.

2 PROPERTIES, PRODUCTION, AND POTENTIAL FOR EXPOSURE
analysis [Wagner 1995; Donaldson and Borm Table 2 lists the main industries around the
1998]. world in which silica exposure has been re-
ported. Virtually any process that involves
movement of earth or disturbance of silica-
Workers in a large variety of industries and oc- containing products such as masonry and con-
cupations may be exposed to crystalline silica crete may expose a worker to silica (see Table 3
because of its widespread natural occurrence for uses of industrial silica sand and gravel).
and the wide uses of the materials and pro- Table 4 presents, from selected States, the
ducts containing it. OSHA compliance officers most frequently recorded occupations of U.S.
found respirable quartz in 6,779 personal sam- residents aged 15 or above whose death certifi-
ples (8-hr TWA) taken in 255 industries that cates list silicosis as an underlying or contri-
were targeted for inspection (excluding mining butory cause of death [NIOSH 1996a]. In addi-
and agriculture). In 48% of the industries, aver- tion, Table 5 lists published case reports of sili-
age overall exposure exceeded the PEL for re- cosis in workers from other industries and
spirable quartz [Freeman and Grossman 1995]. occupations.
Linch et al. [1998] applied an algorithm to
OSHA compliance data from the period 2.4 Sampling and Analytical
19791995 and County Business Patterns 1993
Methods
data [Bureau of the Census 1993] to estimate
the percentage of workers by industry (exclud- Historically, several methods have been used
ing mining and agriculture) exposed to defined to measure worker exposure to airborne crys-
concentrations of respirable crystalline silica talline silica (quartz, cristobalite, or tridymite).
(e.g., 0.05 mg/m3) in 1993. Area samples and These methods differ primarily in the analyti-
samples involving complaints to OSHA were cal technique employed, although they all rely
excluded from the analysis. Although data lim- on a collection procedure that uses a cyclone
itations could have resulted in underestimating for size-selective sampling. Airborne samples
or overestimating the number of workers ex- are collected using a cyclone to remove
posed, the authors found 5 three-digit stan- nonrespirable particles and an appropriate fil-
dardized industrial classification (SIC) codes ter medium (e.g., polyvinyl chloride) to retain
in which an estimated number of workers were the respirable dust fraction. Preparation of the
exposed to concentrations at least 10 times the sample for crystalline silica determination dif-
NIOSH REL: fers depending on the type of analytical tech-
nique used. One of three analytical techniques
is typically used for the quantitative determina-
SIC No. workers tion of crystalline silica: X-ray diffraction
(XRD) spectrometry, infrared absorption (IR)
174 Masonry and plastering . . . . . . . . . 13,800 (1.8%) spectrometry, or colorimetric spectrophoto-
162 Heavy construction . . . . . . . . . . . . 6,300 (1.3%) metry. XRD and IR are the most common tech-
172 Painting and paper hanging . . . . . . 3,000 (1.9%) niques used for crystalline silica analyses. The
332 Iron and steel foundries . . . . . . . . . 800 (0.3%) quantitative limit of detection for these meth-
347 Metal services . . . . . . . . . . . . . . . . 400 (0.2%)
ods ranges from 5 to 10 mg per sample; but the
accuracy is poor, particularly at the low filter
Additional three-digit SICs had a number of loadings (30 mg per sample) that are typically
workers with crystalline silica exposures that collected when workplace concentrations of
were two or five times higher than the NIOSH airborne crystalline silica are near the NIOSH
REL [Linch et al. 1998]. REL of 50 mg/m3 (or 0.05 mg/m3).

Table 2. Main industries and activities around the world in which
silica exposure has been reported
Industry or activity Oper ations and tasks Sou rce m aterials
Agriculture Plowing, harvesting, using machine ry, Soil

burning agricultural waste, processing
agricultural pro ducts
Mining and related milling Most occupations (underground, Ores, associated rock
operations surface, mill) and mines (metal and
nonmetal, coal), rock drilling,
dredging
Quarrying and related milling Crushing stone, sand and gravel Sandstone, granite, flint, sand,
operations processing, stone monum ent cutting gravel, slate, diatomaceous
and abrasive blasting, slate work (e.g., earth
pencil manufacturing), diato mite
calcination
Construction Abrasive blasting of structures and Sand , concrete, rock, soil,

buildings, highway and tunnel mortar, plaster, shingles
construction, excav ation and ea rth
mov ing and digging , maso nry,
concrete work, demolition, dry
sweep ing and brushing, pressurized air
blowing, jack hammering, laying
railroad track, removing rust or p aint,
sanding and scaling, replacement of
asphalt roofing, and hauling, pouring,
mixing, or dumping silica-containing
materials
Glass, including fiberglass Raw material processing, refractory Sand, crushed quartz,
installation and repair refractory ma terials
Cement Raw material processing Clay, sand, limestone,

diatomaceous earth
Abrasives Silicon carbide production, abrasive Sand, tripoli, sandstone

products fabrication
Ceram ics, including bricks, tiles, Mixing, molding, glaze or enamel Clay, shale, flint, sand,
sanitary ware, porcelain, pottery, spraying, finishing, sculpting, firing quartzite, diatomaceous earth
refractories, vitreous enamels
Iron and steel mills Refractory preparation and furnace Refractory material
repair
(Continued)
______________
Sources: IARC [1987; 1997], NIOSH [1979a; 1983a,b; 1996b], DOL, NIOSH [1997], Fulekar and Alam Khan [1995], Jain
et al. [1977], Corn [1980], Webster [1982], Froines et al. [1986], Davis [1996], Weill et al. [1994], Lucas and Salisbury
[1992], Pike [1992], McCunney et al. [1987], Fairfax [1998].

Table 2 (Continued). Main industries and activities around the world in which
silica exposure has been reported
Industry or activity Oper ations and tasks Sou rce m aterials
Silicon and ferro-silicon foundries Raw materials handling, casting, Sand, refractory material
(ferrous and nonferrous) molding and shaking out, abrasive
blasting, fettling, furnace installation
and repair
Metal products, including structural Abrasive blasting Sand
metal, machinery, transportation
equipment
Shipbuilding and repair Abrasive blasting Sand
Rubber and plastics Raw materials handling Fillers (tripoli, diatomaceous
earth)
Paint Raw materials handling, site preparation Fillers (tripoli, diatomaceous
earth, silica flour)
Soaps and cosmetics Manufac turing or occupational use of Silica flour
abrasive soaps and scouring powders
Roofing asphalt felt Filling and granule application Sand and aggregate,
diatomaceous earth
Agricultural chemicals Raw material crushing, handling, Phosphate ores and rock
bagging; or dumping products or raw
materials
Jewelry Cutting, grinding, polishing, buffing, Semiprecious gem s or stones,
etching, engraving, casting, chipping, abrasives, glass
sharpening, sculpting
Arts, crafts, sculpture Pottery firing, ceramics, clay mixing, Clays, glazes, bricks, stones,
kiln repairs, abrasive blasting, sand rocks, minerals, sand, silica
blasting, engraving, cutting, grinding, flour
polishing, buffing, etching, engraving,
casting, chipping, sharpening,
sculpting
Dental material Sand blasting, polishing Sand, abrasives
Boiler scaling Coal-fired boilers Ash and concretions
Auto mob ile repa ir Abrasive blasting, sanding, removing Sand , metals, p riming p utty
paint and rust

Table 3. Industrial silica sand and gravel sold or used
by U.S. producers in 1994, by major end use
Gen eral use End use
Sand:
Glass-making Containers, flat (plate and window), specialty, fiberglass (unground or ground)
Foundry work Mo lding and core, molding and core facing (ground), refractory
Metallurgical work Silicon carbide, flux for metal smelting
Abrasive work Blasting, scouring cleansers (ground), sawing and sanding, chemicals (ground and
unground)
Fillers Rub ber, p aints, putty, whole grain fillers/building p roducts
Ceramics Pottery, brick, tile
Filtration W ater (municipal, county, local), swimming pool, others
Petroleum manufacturing Hydraulic fracturing, well packing, and cementing
Recreation Golf course, baseball, volleyball, play sands, beaches, traction (engine), roofing
granules and fillers, other (ground silica or whole grain)
Gravel Silicon, ferrosilicon, filtration, nonmetallurgical flux, other
Sources: IARC [1997]; BOM [1994].

Table 4. Most frequently recorded occupations of U.S. residents aged 15 or above
whose death certificates list silicosis as an underlying or contributory
cause of deathselected States, 19911992*
COC Occupation Number %
616 Mining machine operator 39 16.0
889 Laborer, except construction 29 11.9
019 Manager or administrator, not elsewhere classified 11 4.5
633 Supervisor or precision production occupations 11 4.5
453 Janitor, cleaner 8 3.3
719 Molding, casting machine operator 8 3.3
243 Supervisor or proprietor of sales occupations 6 2.5
844 Operating engineer 6 2.5
637 Machinist 5 2.1
787 Hand m olding, casting, and forming occupations 5 2.1
All other occupations 109 44.9
Occupation not reported 6 2.5
TOTAL 243 100 .1

Source: NIOSH [1996a].
*
Data for 19851990 are reported in Table 411 of NIOSH [1994d].
COC: 1980 census occupation code.
Column does not add to 100.0 because of rounding.

Table 5. Other occupations* reporting cases of silicosis in workers
Industry or occupation Reference
Agriculture industry or forestry worker Fennerty et al. [1983]; Dynnik et al. [1981]; Beaumont et al. [1995]
Brewery worker Nemery et al. [1993]
Confectioner Canessa et al. [1990]
Crystal cutter Suskovic et al. [1990]
Drycleaning worker Seitz et al. [1982]
Filter candle production worker Vigliani and Mottura [1948]
Grave digger and well digger al-Kassimi et al. [1991]
Kaolin worker Rodriguez et al. [1985]
Metal polisher Malik et al. [1985]
Pit digger de Barros Hatem and Cavalcanti [1990]
Souvenir casting worker Carel et al. [1994]
W oodworker Thoreux et al. [1990]

*
Includes only occupations not listed in Tables 2 or 4.

2.4.1 Sampling Methods Cyclones and filter cassettes should be leak

tested to avoid gross failure in the field. The
Current sampling methods for crystalline silica cyclones may be tested using a simple
involve the use of a cyclone attached to a filter pressure- (or vacuum-) holding test. The filter
cassette to collect the respirable fraction of the cassette should also be checked for leakage
airborne particulate. To minimize measure- while attached to the cyclone. Two approaches
ment bias and variability, these samplers to testing the cassettes have been used. A mi-
should conform to the criteria of the Interna- cromanometer has been used to measure the
tional Organization for Standardization (ISO), pressure drop across a single type of cassette
the European Standardization Committee and compare it with the average pressure drop
(CEN), and the American Conference of Gov- across well-sealed cassettes [Van den Heever
ernmental Industrial Hygienists (ACGIH) for 1994]. An alternative approach uses a particle
collecting particles of the appropriate size [ISO counter to measure the penetration of submicro-
1991; CEN 1992; ACGIH 2001]. Also, the cy- meter ambient aerosol through the cassette,
clone should exhibit sufficient conductivity to with the percentage of penetration serving as
minimize the electrostatic effects on particle an indicator of leakage [Baron 2001]. Mea-
collection. Cyclones typically used for crys- surement of cassette leakage by several labora-
talline silica measurements include the Dorr- tories indicates that significant leakage can
Oliver 10-mm nylon cyclone and the Higgins- occur in certain situations. Cassettes should be
Dewell conductive cyclone. These cyclones assembled using a press, and they should be
have been evaluated for their compliance with routinely checked for leakage.
the ISO/CEN/ACGIH respirable aerosol sam-
pling convention. Flow rates of 1.7 L/min for 2.4.2 Analytical Methods
the Dorr-Oliver cyclone and 2.2 L/min for the
Higgins-Dewell cyclone provide minimum 2.4.2.1 XRD Spectrometry
bias for a wide range of particle size distribu-
tions that are likely to occur in the workplace
XRD methods used for crystalline silica de-
[Bartley et al. 1994]. The Dorr-Oliver 10-mm
cyclone is required by MSHA, and the Higgins- termination include NIOSH Method 7500
Dewell cyclone is used in the United Kingdom. [NIOSH 1998], OSHA Method ID142
Recently, the GK2.69 cyclone [Kenny and [OSHA 1996], MSHA Method P2 [MSHA
Gussman 1997] has become available with a 1999], and the Health and Safety Executive
sampling rate equal to 4.2 L/min. The GK2.69 (HSE) Method for the Determination of Haz-
cyclone is expected to be at least as adequate as ardous Substances (MDHS) 51/2 [HSE 1988].
the nylon cyclone for conforming to the ISO/ Details of these methods are presented in
CEN/ACGIH respirable aerosol sampling con- Table 6. XRD is capable of distinguishing the
vention; and it may be preferable for silica three prevalent polymorphs of crystalline silica
sampling since it is conductive, has well- (quartz, cristobalite, and tridymite) and can si-
defined dimensional characteristics, and can multaneously analyze for each polymorph
be used at higher flow rates for better mass sen- while correcting for interferences that may be
sitivity. Because each type of cyclone exhibits present on the sample [Madsen et al. 1995]. Al-
specific particle collection characteristics, the though most samples collected in industrial
use of a single cyclone type for each applica- workplaces are relatively free of mineral inter-
tion would be advisable until evidence be- ferences, an XRD scan of some samples should
comes available indicating that bias among be performed to ensure the absence of interfer-
cyclone types will not increase laboratory- ences through confirmation of the correct peak
to-laboratory variability. ratios for the three largest peaks.

Table 6. XRD* sampling and analytical methods for crystalline silica
NIOSH OSHA MSHA
Item M ethod 7500 M ethod ID-142 M ethod P-2 M DHS 51/2
Silica polymorph Quartz, cristobalite, Quartz, cristo balite Quartz, cristo balite Quartz
tridymite
Sampler 10-mm nylon 10-mm nylon 10-mm nylon Higg ins-De well
cyclone, 1.7 L/min; Dorr-Oliver Dorr-Oliver cyclon e, 1.9 L/min
Higg ins-De well cyclon e, 1.7 L/min cyclon e, 1.7 L/min
cyclon e, 2.2 L/min
Filter 37-mm, 5-m 37-mm, 5-m 37-mm, 5-m 25-mm, 5-m

PVC membrane PVC membrane PVC membrane PVC membrane
Volume 4001,000 L; total 408816 L; total 4001,000 L; total $456 L; total

dust < 2 mg dust < 3 mg dust < 3 mg dust < 2 mg
Filter preparation RF plasma asher, Disso lve filter in RF plasma asher None
muffle furnace, or THF
filter dissolution in
THF
Redeposition On 0.45-m silver On 0.45-m silver On 0.45-m silver None

membrane filter membrane filter membrane filter
Drift correction Silver internal Silver internal Silver internal External standard
standard standard standard (e.g., aluminum
plate)
X-ray source Cu K " ; 40 kV, Cu K " ; 40 kV, Cu K " ; 55 kV, Cu K " ; 45 kV,
35 mA 40 mA 40 mA 45 mA
Calibration Susp ensions of SiO 2 Susp ensions of SiO 2 Suspensions of Sampling from a
in 2-propanol in 2-propanol SiO 2 in 2-propanol generated
(deposited on silver (deposited on silver (deposited on silver atmosphere of
membrane filter) membrane filter) membrane filter) standard q uartz dust
Proficiency testing PAT PAT PAT WASP
Range (g quartz) 202000 50160 (validation 20500 502000

range)
LOD (g quartz) 5 (estimated) 10 5 3
Precision CV = 10 % @ CV = 5 % @ 50 g
= 0.08 = 0.106 @
50160 g 20500 g
50200 g
*Abbreviations: Cu = copper; CV = coefficient of variation (equivalent to RSD); = pooled coefficient of variation;

K" = electron ionization energy; kV = kilovolt(s); LOD = limit of detection; mA = milliampere(s); MDHS = Methods for
the Determination of Hazardous Substances (Health and Safety Executive, United Kingdom); MSHA = Mine Safety and
Health Administration; NIOSH = National Institute for Occupational Safety and Health; OSHA = Occupational Safety
and Health Administration; PAT = proficiency analytical testing; PVC = polyvinyl chloride; RF = radio frequency;
RSD = relative standard deviation; = pooled relative standard deviation (equivalent to ); THF = tetrahydrofuran;
WASP = Workplace Analysis Scheme for Proficiency; XRD = X-ray diffraction.

2.4.2.2 IR Spectrometry onto 25-mm silver membrane filters (NIOSH

Method 7500 and OSHA Method ID142). IR
IR methods used for crystalline silica deter- samples can be measured directly (MDHS 37),
mination include NIOSH Methods 7602 and redeposited on an acrylic copolymer mem-
7603 [NIOSH 1994a,c], MSHA Method P7 brane filter (NIOSH Method 7603 and MSHA
[MSHA 1994], and MDHS 37 and 38 [HSE Method P7 ), or incorporated into a potassium
1987, 1984]. Details of these methods are pre- bromide (KBr) pellet (NIOSH Method 7602
sented in Table 7. Although IR is less specific
and MDHS 38). Techniques used for redepos-
than XRD (IR methods cannot readily distin-
iting the sample (both IR and XRD) are diffi-
guish crystalline silica polymorphs), the tech-
cult to perform at low sample loadings and
nique is less expensive and can be optimized
require the laboratory analyst to demonstrate
for measuring quartz in well-defined sample
good intralaboratory reproducibility. How-
matrices [Madsen et al. 1995; Smith 1997;
ever, these techniques can be optimized by
Hurst et al. 1997]. Samples that contain other
silicates (such as kaolinite) and amorphous sil- preparing multiple working standards from
ica can present interferences in the analyses. multiple suspensions of calibration standards
Also, a potential for bias exists when correct- and by ensuring that the sample is redeposited
ing for matrix absorption effects, with an in- evenly as a thin layer on the filter. No statisti-
creasing risk of bias at lower quartz concen- cally significant difference has been observed
trations. between ashing the filter (muffle furnace and
low-temperature asher) and dissolving the fil-
2.4.2.3 Colorimetric Spectrophotometry ter by tetrahydrofuran before redepositing the
sample [Eller et al. 1999a].
The NIOSH colorimetric method for crystal-
line silica (NIOSH Method 7601) [NIOSH The instrument response of all three analytical
1994b] is significantly less precise than IR or techniques is influenced by the size of the par-
XRD methods. The colorimetric analytical ticles in the sample. With XRD, the diffraction
method exhibits a nonlinear dependence on the intensity (as measured by peak height) can
mass of crystalline silica present [Eller et al. vary considerably with particle size, with
1999a]. The linear range of the method is lim- smaller particles showing lower intensities
ited, and the blank values for samples can be [Bhaskar et al. 1994]. The sensitivity of IR
high (20 mg silica or higher) [Talvitie 1951, analyses decreases with increasing particle
1964; Talvitie and Hyslop 1958]. High intra- size. The colorimetric method requires the use
laboratory variability of the method (up to of a precisely timed heating step with phospho-
twice that of IR or XRD) has been noted in ric acid to digest amorphous silica and silicates
studies conducted in the Proficiency Analyti- during sample preparation, causing a possible
cal Testing Program (PAT) [Shulman et al. loss of some small crystalline silica particles
1992]. The colorimetric method cannot distin- [Eller et al. 1999a]. Since particle size affects
guish between silica and silicates, since it is the sensitivity of all three analytical tech-
based on the measurement of silicon. niques, the particle size distribution of the cal-
ibration standard should closely match the
2.4.2.4 Factors Affecting the size of the particles retained on the collected
Sensitivity and Accuracy of sample.
Analytical Techniques
For all analytical techniques, strict adherence
Samples prepared for XRD analyses are mea- to standardized procedures is necessary to pro-
sured directly (MDHS 51/2) or are redeposited duce accurate results. Specifically, appropriate

Table 7. IR* sampling and analytical methods for crystalline silica
NIOSH NIOSH
Item M ethod 7602 M ethod 7603 M SHA P7 M DHS 37 M DHS 38
Matrix Coal mine dust Coal mine dust
Sampler 10-mm nylon 10-mm nylon 10-mm nylon Higg ins-De well Higgins-
cyclone, 1.7 L/min; cyclone, Dorr-Oliver cyclone, Dewell
Higg ins-De well 1.7 L/min; cyclone, 1.9 L /min cyclone,
cyclon e, 2.2 L/min Higg ins-De well 2.0 L /min 1.9 L /min
cyclone,
2.2 L /min
Filter 37-mm filter; 5-m 37-mm filter; 37-mm filter; 37-mm filter; 37-mm filter;
PVC or MCE 5-m PVC 5-m PVC 5-m PVC 5-m PVC
membrane membrane membrane, membrane membrane
preweighed
Volume 400800 L; total 3001,000 L; Not stated $456 L; total $456 L;

dust <2 mg total dust <2 mg dust <1 mg total dust
<0.7mg
Filter RF plasma asher or RF plasma RF plasma asher None Muffle furnace

preparation muffle furnace asher or muffle
furnace
Analytical Mix residu e with Redeposit on Redepo sit on None Mix residue
samp le KB r, press 0.45 -m acrylic 0.45-m acrylic with KBr,
preparation 13-mm pellet copolymer filter copolymer filter press 13-mm
pellet
Standard Polystyrene film Polystyrene film Polystyrene film Polystyrene film Polystyrene
film
Calibration Quartz diluted in Standard Standard Sampling from Sampling from

KBr suspension of suspension of a generated a generated
quartz in quartz in atmosphere of atmosphere of
2-propanol 2-propanol standard q uartz standard q uartz
dust dust
Proficiency PAT PAT PAT WASP WASP

testing
Range 10160 30250 25250 101,000 5700

(g quartz)
LOD 5 (estimated) 10 (estimated) 10 Varies with Varies with

(g quartz) particle size particle size
___________
See footnote at end of table. (Continued)

Table 7 (Continued). IR* sampling and analytical methods for crystalline silica
NIOSH NIOSH
Item M ethod 7602 M ethod 7603 M SHA P7 M DHS 37 M DHS 38
Precision CV = 510 % CV = 5 % CV = 5 %
<0.15 = 0.098
@ 100500 g @ 50 g @ 50 g
@ 30g @ 100500g
*Abbreviations: CV = coefficient of variation (equivalent to RSD, relative standard deviation); IR = infrared absorption;
KBr = potassium bromide; MCE = methyl cellulose ester; MDHS = Methods for the Determination of Hazardous
Substances (Health and Safety Executive, United Kingdom); MSHA = Mine Safety and Health Administration;
NIOSH = National Institute for Occupational Safety and Health; LOD = limit of detection; PAT = proficiency analytical
testing; PVC = polyvinyl chloride; RF = radio frequency; = pooled relative standard deviation (equivalent to
pooled coefficient of variation); WASP = Workplace Analysis Scheme for Proficiency.

calibration of the technique has been shown to accuracy criterion [NIOSH 1995b], which re-
be critical in the accurate measurement of crys- quires better than 25% accuracy at concen-
talline silica [Eller et al. 1999b]. Also, it is es- trations of expected method application. Accu-
sential that only standard reference materials racy, as a percentage of true concentration val-
from the National Institute of Standards and ues, is defined in terms of an interval expected
Technology (NIST) (for which particle size to contain 95% of (future) measurements. To
and phase purity has been established) be used account for uncertainty in method evaluations,
to prepare calibration curves for quartz (1878a) the upper 95% confidence limit on the accu-
and cristobalite (1879a) [Eller et al. 1999a]. No racy is measured and used in the criterion.
standard reference material for tridymite is Generally, the accuracy of a method is mea-
available, since this silica polymorph rarely sured over a range of concentrations brack-
exists in the workplace. However, a well- eting the OSHA PEL. Use of a range of mea-
characterized sample of tridymite of the appro- surements means that accuracy is assured
priate particle size is available from the U.S. both at concentrations below the PEL (for pos-
Geological Survey* and can be used as a refer- sible use in action level determinations) and,
ence standard.
more significantly, at the PEL (where method
results must be legally defensible).
Direct-on-filter techniques are used by the
United Kingdom, the European Union, and
Australia [Madsen et al. 1995]. These tech-
NIOSH has evaluated both the XRD silica
niques require less time and labor than others
and are amenable to both XRD and IR analyses method (NIOSH Method P&CAM 259, the
[Lorberau et al. 1990]. However, direct-on-fil- forerunner to NIOSH Method 7500) [NIOSH
ter techniques are affected by the manner in 1979b] and an IR silica method (MSHA Method
which the particles are deposited on the filter P7, equivalent to NIOSH Method 7603) in a
sample (particle deposition may be nonuni- collaborative test among several laboratories
form). Thus care must be taken when choosing [NIOSH, BOM 1983]. One result of the test
the area of the filter to measure so that results was that the accuracy of the methods was
can be compared with other methods. Sample estimated by evaluating the intralaboratory
overloading is possible for a sample collected variability at various filter loadings. The con-
over a full work shift. centrations to which these filter loadings corre-
spond depend on the flow rate of the pre-
2.4.3 Feasibility of Measuring sampler used. Experimental conditions and re-
Crystalline Silica at sults relevant to the derivation of these esti-
Various Concentrations mates are summarized in Tables 8 and 9. The
results of the collaborative tests indicate that
The efficacy of sampling and analytical meth-
both the XRD and IR methods tested meet the
ods for measuring concentrations of hazardous
NIOSH accuracy criterion [NIOSH 1995b]
materials may be established using the NIOSH
over the range of filter loadings measured.
Currently, OSHA uses the 10-mm nylon cy-
clone at a sampling rate of 1.7 L/min for sam-
*
Tridymite reference material may be obtained from pling crystalline silica. The concentrations
Dr. Stephen A. Wilson, U.S. Geological Survey, Box relevant to the collaborative test conditions are
25046, MS 973, Denver, CO 80225 (telephone:
3032362454; FAX: 3032363200; e-mail: swilson
listed in Tables 10 and 11 and assume an 8-hr
@usgs.gov; Web site: http://minerals.cr.usgs.gov/ sampling period. As indicated in Tables 10 and
geochem). 11, the traditional nylon cyclone meets the

Table 8. Intralaboratory results for evaluation of XRD silica method
Filter loading
Item 69.4 :g 98.4 :g 204 :g
Degrees of freedom 12 11 12
*,
RSD for sampling and analytical methods (%) 8.8 6.3 8.1
Source: NIOSH, BOM [1983].

*
RSD = relative standard deviation. RSD for sampling and analytical methods represents the RSD in
mass estimates, accounting for intersampler and analytical variability.

Implications for XRD: Pooled filter levels and pump error (assumed to be <5%) indicate that the
overall imprecision is as follows: Total RSD for sampling and analytical methods is 9.3%. Therefore,
the upper 95% confidence limit on the accuracy (35 degrees of freedom) is 21%.
Table 9. Intralaboratory results for evaluation of IR silica method

Filter loading
Item 67.2 :g 99.7 :g 161 :g
Degrees of freedom 10 12 11
*,
RSD for sampling and analytical methods (%) 5.8 7.8 7.4
Source: NIOSH, BOM [1983].

*
RSD = relative standard deviation. RSD for sampling and analytical methods represents the RSD in
mass estimates, accounting for intersampler and analytical variability.

Implications for IR: Pooled filter levels and pump error (assumed to be <5%) indicate that the
overall imprecision is as follows: Total RSD for sampling and analytical methods is 7.1%.
Therefore, the upper 95% confidence limit on the accuracy (33 degrees of freedom) is 17%.

Table 10. XRD method evaluation: concentration ranges bracketing applicable
exposure limits for which the NIOSH accuracy criterion is met*
(:g/m3 )
Filter loading
Ap plicable
Cyclone and samp ling rate 69.4 :g 98.4 :g 204 :g expo sure limit
Nylon cyclone, 1.7 L/min 85 121 251 100
GK 2.69 cyclone, 4.2 L/min 34 49 102 50

*
Eight-hour sampled masses are combined with results of NIOSH , BOM [1983].
Table 11. IR method: concentration ranges bracketing applicable exposure limits

for which the NIOSH accuracy criterion is met*
(:g/m3 )
Filter loading
Ap plicable
Cyclone and samp ling rate 6.72 :g 99.7 :g 161 :g expo sure limit
Nylon cyclone, 1.7 L/min 83 123 198 100
GK 2.69 cyclone, 4.2 L/min 34 50 80 50

*
Eight-hour sampled masses are combined with results of NIOSH , BOM [1983].

accuracy criterion over a range of concentra- oratory collaborative tests can be used to estab-
tions bracketing 100 mg/m3. lish confidence limits on its accuracy. The
results of the collaborative tests indicate that
Since the GK2.69 cyclone is expected to con- the GK2.69 cyclone meets the accuracy crite-
form to the ISO/CEN/ACGIH respirable aero- rion over a range of concentrations bracketing
sol sampling convention, the NIOSH intralab- 50 mg/m3, as illustrated in Tables 10 and 11.

3 Human Health Effects
3.1 Epidemiologic Considerations health survey and comparison with respira-
in Occupational Respiratory tory function in nongranite workers. Cross-
Disease Studies sectional studies have two disadvantages:
3.1.1 Study Designs Usually only the survivor population

is examined. Retired, former, or de-
Epidemiology is the study of patterns of dis- ceased workers are not included, possi-
ease occurrence in human populations and the bly resulting in an underestimate of the
factors that influence those patterns [Lilienfeld disease prevalence.
and Stolley 1994]. Epidemiology is the pri-
mary science used to study silica-related dis- It may be impossible to determine
eases in workers. Most epidemiologic studies whether exposure preceded the disease
of silica-exposed workers discussed in this re- if both are measured at the same time.
view are cross-sectional studies (i.e., preva-
lence studies) or retrospective (i.e., historical) Many epidemiologic studies of silica-related
cohort studies. Cross-sectional studies meas- diseases are retrospective cohort morbidity or
ure symptom or disease occurrence in a se- mortality studies. In this approach, the ill-
lected population at one point in time. An ex- nesses, deaths, and exposures (surrogate or re-
ample of a cross-sectional study design would constructed) of an entire cohort (e.g., all work-
be the spirometric testing of lung function in a ers ever employed in one foundry) are
group of granite shed workers during an annual followed forward from a time in the past to a
Photograph by Kenneth Linch, NIOSH

Construction workers drilling holes in concrete pavement during highway repair.

3 HUMAN HEALTH EFFECTS
designated time in the future, and the number higher in compensated silicotics when
and causes of deaths that occur in that interval compared with those of silicotics ascer-
are assessed. Exposures for the followup pe- tained from other clinical sources (i.e.,
riod may be reconstructed from historical in- hospital or registry data).
formation or a surrogate measure such as dura-
tion of employment. The mortality of the Information bias involves misclassifi-
cohort is then compared with the mortality of a cation of study subjects by disease or ex-
standard population. For example, Steenland posure status [Checkoway et al. 1989].
and Brown [1995b] used a retrospective study An example of disease (silicosis) mis-
design to examine the mortality of a cohort of classification occurred in a study of
white male underground gold miners em- North Carolina dusty trades workers
ployed for at least 1 year between 1940 and [Amandus et al. 1991; Rice et al. 1986]:
1965. The miners were followed from their a re-evaluation of the chest X-rays found
first date of mining employment to their date of that 104 of the 370 cases categorized
death or until the end of 1990, whichever came as silicosis were actually International
first. Their mortality was then compared with Labour Organization (ILO) category 0
that of the U.S. population or the county where (nonsilicotic) [Amandus et al. 1992].
the mine was located. A disadvantage of silico- Sources of exposure assessment errors
sis mortality studies that use death certificate include instrument error, incorrect im-
data is that silicosis cases could be under- putation of exposure when data are
ascertained even when contributing causes of missing, and data extrapolation errors
death are included, as suggested by a study of [Checkoway 1995]. Misclassification of
silicosis mortality surveillance in the United exposure may occur in retrospective co-
States [Bang et al. 1995]. hort studies of silicosis when quantita-
tive dust exposure measurements are
mathematically converted from particle
3.1.2 Sources of Bias
counts to gravimetric respirable silica
Three main (but not mutually exclusive) types equivalents.
of bias may affect the results of epidemiologic
studies of silica-exposed workersselection Confounding variables are factors that
bias, information bias, and confounding are related to exposure and are also inde-
[Checkoway 1995]: pendent risk factors for the disease under
study [Checkoway 1995]. Most studies
Selection bias originates from the of silica-related diseases controlled for
method of choosing study subjects. This confounding factors such as age and race
type of bias is a common criticism of by study design or data analysis. Con-
lung cancer studies of compensated founding from cigarette smoking is an
silicotics because silicotic workers who important concern in studies of lung can-
sought compensation for their disease cer, bronchitis, asthma, emphysema,
may differ from all silicotics in symp- chronic obstructive pulmonary disease
toms, radiographic changes, social and (COPD), and lung function. Confound-
psychological factors, and industry ing of an exposure-disease relationship
[Weill and McDonald 1996; McDonald by cigarette smoking is less likely when
1995]. However, Goldsmith [1998] re- an internal comparison group is used
viewed this question and concluded that e.g., when both groups are from the
lung cancer risk estimates were not same plant [Siemiatycki et al. 1988].

(Some studies in this review used exter- conducted to investigate the surface charac-
nal comparison populations.) Most of teristics of crystalline silica particles and their
the lung cancer studies among under- influence on fibrogenic activity [Bolsaitis and
ground miners did not control for the ef- Wallace 1996; Fubini 1997, 1998; Castranova et
fects of other carcinogens that may have al. 1996; Donaldson and Borm 1998; Erdogdu
been present, such as arsenic, radon and Hasirci 1998]. These researchers found that a
progeny, and diesel exhaust (see Sec- number of features may be related to silica
tion 3.4.1). cytotoxicity. Further research is needed to asso-
ciate the surface characteristics with occupa-
The effects of bias discussed here can be mini- tional exposure situations and health effects
mized by applying epidemiologic methods. [Donaldson and Borm 1998]. Such exposure sit-
Description of appropriate methodology is uations may include work processes that produce
available in epidemiology textbooks. freshly fractured silica surfaces [Bolsaitis and
Wallace 1996; Vallyathan et al. 1995] or that in-
volve quartz contaminated with trace elements
3.2 Silicosis such as iron [Castranova et al. 1997].
3.2.1 Definition
A worker may develop one of three types of sil-
Silicosis most commonly occurs as a diffuse icosis, depending on the airborne concentra-
nodular pulmonary fibrosis. This lung disease tion of respirable crystalline silica: (1) chronic
(which is sometimes asymptomatic [NIOSH silicosis, which usually occurs after 10 or more
1996b]) is caused by the inhalation and deposi- years of exposure at relatively low concentra-
tion of respirable crystalline silica particles tions; (2) accelerated silicosis, which develops
(i.e., particles <10 m in diameter) [Ziskind et 5 to 10 years after the first exposure; or (3) acute
al. 1976; IARC 1987]. According to a report silicosis, which develops after exposure to
from the U.S. Surgeon General [DHHS 1985], high concentrations of respirable crystalline
cigarette smoking has no significant causal silica and results in symptoms within a period
role in the etiology of silicosis. Probably ranging from a few weeks to 5 years after the
the most important factor in the development initial exposure [NIOSH 1996b; Parker and
of silicosis is the dose of respirable silica- Wagner 1998; Ziskind et al. 1976; Peters
containing dust in the workplace settingthat 1986]. The symptoms of accelerated silicosis
is, the product of the concentration of dust con- are similar to those of chronic silicosis, but
taining respirable silica in workplace air and the clinical and radiographic progression is rapid.
percentage of respirable silica in the total dust. Also, fibrosis may be irregular and more dif-
Other important factors are (1) the particle size, fuse [Banks 1996; Seaton 1995; Silicosis and
(2) the crystalline or noncrystalline nature of Silicate Disease Committee 1988] or not ap-
the silica, (3) the duration of the dust exposure, parent on the chest radiograph [Abraham and
and (4) the varying time period from first expo- Weisenfeld 1997]. Acute silicosis is typically
sure to diagnosis (from several months to more associated with a history of high exposures
than 30 years) [Banks 1996; Kreiss and Zhen from tasks that produce small particles of
1996; Hnizdo and Sluis-Cremer 1993; Hnizdo et airborne dust with a high silica content,
al. 1993; Steenland and Brown 1995a; ATS such as sandblasting, rock drilling, or quartz
1997]. Experimental evidence supporting the in- milling [Davis 1996]. The pathologic charac-
fluence of these factors has recently been re- teristics of acute silicosis (sometimes referred
viewed [Mossman and Churg 1998; Heppleston to as silicoproteinosis) resemble those of alve-
1994]. Many in vitro studies have been olar proteinosis [Wagner 1994; Davis 1996].

Pulmonary fibrosis may not be present in acute predicted the occurrence of at least one case
silicosis [NIOSH 1996b]. of radiographic silicosis per 100 workers at
cumulative exposures approximately equal
Epidemiologic studies of gold miners in South to the OSHA and MSHA PELs and the
Africa, granite quarry workers in Hong Kong, NIOSH REL over a 40- or 45-year working
metal miners in Colorado, and coal miners in lifetime (see appendix for the PELs and REL).
Scotland have shown that chronic silicosis may Three studies predicted prevalences of 47% to
develop or progress even after occupational 95% at the OSHA PEL. Each study followed a
exposure to silica has been discontinued cohort of miners for at least three decades from
[Hessel et al. 1988; Hnizdo and Sluis-Cremer first employment in the industry [Kreiss and
1993; Hnizdo and Murray 1998; Ng et al. Zhen 1996; Hnizdo and Sluis-Cremer 1993;
1987; Kreiss and Zhen 1996; Miller et al. Steenland and Brown 1995a]. Studies of
1998]. Therefore, removing a worker from ex- foundry workers [Rosenman et al. 1996],
posure after diagnosis does not guarantee that hardrock miners [Muir et al. 1989a,b; Muir
silicosis or silica-related disease will stop pro- 1991], and workers in the diatomaceous earth
gressing or that an impaired workers condi- industry [Hughes et al. 1998] followed work-
tion will stabilize [Parker and Wagner 1998; ers for less than 30 years (mean) and predicted
Weber and Banks 1994; Wagner 1994]. prevalences of 1% to 3%. The studies pre-
sented in Table 12 predicted that approxi-
3.2.2 Epidemiologic mately 1 to 7 silicosis cases per 100 workers
Exposure-Response would occur at respirable quartz concentra-
Models of Silicosis tions of 0.025 mg/m3half the NIOSH REL of
0.05 mg/m3with the contingencies and ex-
This section reviews published epidemiologic ceptions noted in Table 12. However, that con-
studies that provide evidence of an exposure- centration cannot be measured accurately at
response relationship for crystalline silica this time for the reasons given in Section 2.4.
and silicosis using cumulative exposure data.
Exposure-response models based on cumula- Table 12 does not include a cohort study of
tive exposure data can predict silicosis risk for 1,416 coal miners exposed to coal dust with
a particular silica dust exposure over a period quartz concentrations ranging from 0.4% to
of time. Epidemiologic studies that provided 29.4% of respirable dust [Miller et al. 1998].
evidence of an exposure-response relationship This study predicted pneumoconiosis risks for
for silica and silicosis on the basis of other 47 men with a profusion of median small
kinds of exposure data (e.g., duration of expo- opacities of ILO category $2/1 (i.e., 2/1+), a
sure) have been reviewed elsewhere [EPA higher category of radiographic abnormality
1996; Davis 1996; Hughes 1995; Rice and than reported in the studies listed in Tables 12
Stayner 1995; Seaton 1995; Steenland and and 13. Logistic regression models predicted
Brown 1995a; Goldsmith 1994a; WHO 1986]. that the risk of small opacities of 2/1+ at the
time of followup examination would be about
Table 12 summarizes the published studies that 5% for miners exposed to a mean respirable
predict the incidence or prevalence of radio- quartz concentration of 0.1 mg/m3 and about
graphic silicosis based on models of cumula- 2% for miners exposed to a mean respirable
tive exposure to respirable crystalline silica. quartz concentration of 0.05 mg/m3 for about
Table 13 presents details about the cohorts, 15 years [Miller et al. 1998]. The predicted
quartz content of the dust, followup periods, risks increased with cumulative exposure to re-
and limitations of each study. All of the studies spirable quartz dust.

Table 12. Predicted incidence or prevalence of silicosis following exposure to selected concentrations of
respirable quartz dustbased on modeling of cumulative exposure over a 45-year working lifetime
Selected mean Predicted incidence or

concentration of M ean time since first M aximum time since prevalence o f silicosis,
respirab le quartz dust quartz exposure first quartz exposure ILO category $ 1/1
Study and cohort (mg/m 3) (yr) (yr) (cases/10 0 w orkers)
Hnizdo and S luis-Cremer [1 993 ], 0.05 36 * 50 * 13

2,235 So uth African gold miners 0.10 70
Hughes et al. [1998], 2,34 2 U .S. 0.05 11.5 46 1.5 4 ,**
Respirable Crystalline Silica

workers in a diatomaceous earth 0.10 4 17 ,**
mining and p rocessing facility
Kreiss and Zhen [1996], 100 U.S. 0.05 41.6 * 66 * 30 ,
hardrock miners and 34 comm unity 0.10 33.5 68 90 ,
controls
Muir et al. [1989 a,b] and M uir [19 91], 0.05 18 38 * 0.090.62
2,109 Canadian gold and uranium
miners
Ng and C han [1994], 338 Hong K ong 0.045 ,*** 6
granite workers
Rosenman et al. [1 996 ], 1,07 2 U .S. 0.05 28 >30 2
gray iron foundry workers 0.10 3
Steenland and Brown [1995a], 3,330 0.05 37 73 10 ****
U.S. gold miners 0.09 47 ****
*
Silicotic miners.

Estimate reported in Rice and Stayner [1995].

Approximate.

Primarily cristobalite dust. Cumulative risk of small opacities $ ILO category 1/0 and/or large opacities. For 1,452 workers with an average crystalline silica exposure
# 0.50 mg/m3 ; 1,138 (78%) of these workers were hired in 1950 or later.
**
Primarily cristobalite dust. Cumulative risk of small opacities $ ILO category 1/0 and/or large opacities. For 357 workers with an average crystalline silica exposure
>0.50 mg/m3; 319 (89%) of these workers were hired before 1950.

Based on cumulative silica exposure model with 10 yr of post-employment followup.

Nonsilicotic miners.

No post-employment followup and no retired miners included. The range includes five estimates (one for each reader). Estimate reported in Rice and Stayner [1995].
***
Based on a 50-year-old worker with cumulative silica exposure of 2 mg/m3@yr.

Not reported. Mean duration of employment was 17 yr for all workers and 27.5 yr for workers in the highest category of cumulative silica exposure.

ILO category $ 1/0. Based on a 40-yr working lifetime and controlling for pack-years of cigarette smoking, race, and silica exposure other than in the foundry under study.

25
Steenland [1998].
****
Includes 141 cases documented on death certificate only. Estimated risk not adjusted for age or calendar time [Steenland 1997].
26
Table 13. Summary of epidemiologic studies of silicosis with cumulative dust exposure data and silicosis risk estimates
Definition of silicosis,
mean duration of
Referen ce, employment, and Silica (quartz)
country, and mean yr since first content of M easure of
study design Cohort quartz exposure respirab le dust association Com ments
Hnizd o and S luis- 2,235 white underground ILO * catego ry $1/1and 30% after heat Cumu lative risk Authors speculated that these
Cremer [1 993 ], South gold miners who were rounded opacities and acid silicosis risk estimates were higher
Africa, cohort study aged 45 to 54 at time of (313 cases); 23.5 yr for treatment [B eadle than estimates for Canadian miners
med ical examinatio n in total co hort an d 26 .9 and Bradley reported by Muir et al. [1989a,b]
19681971 , started yr for cases; 36 yr for 1970]. and M uir [1991 ] because (1) dust
working after 1938, cases. exposure may have been under-
worked $10 yr, and were estimated, (2) Sou th African gold
followed until 1991. mine d ust may b e mo re fibro genic
than Canadian mine dust, (3) average
proportion of quartz may be >30%,
(4) there may have been differences
in age at end of radiological follow-
up, and (5) exposures for Canadian
miners (Hnizdos [19 95] resp onse
to Hughes and Weill [1995]) may
have been overestimated.

See footnotes at end of table. (Continued)
Table 13 (Continued). Summary of epidemiologic studies of silicosis with cumulative dust exposure data and silicosis risk estimates
mean duration of
Hughes et al. [1998], 2,342 white male workers Small opacities $ILO Natural diatomite, Cumu lative risk 82 workers had radiographs taken
United States, retro- emp loyed at least 1 yr profusion category 1/0 3%; calcined after retirementdevelopment of

spective cohort study between 1 942 and 1 987 in and/or large opacities diatomite, 20%; opacities was not recorded for other
one diatomaceous mining (81 cases); 5.54 yr; flux-calcined workers after they left emp loy-
and processing facility. 11.5 yr. diatomite, 60% ment. Quantitative air-monitoring
Exp osure -respo nse analy- (see comments). data were available after 1948;
ses included the 1,809 men respirable dust concentrations be-
with a radiograph taken fore 194 8 were estimated [Seixas
more than 1 month after et al. 1997]. Cum ulative risk esti-
hire. mates for radiographic opacities
were lower for workers who were
hired after 1950 and who had lower
average exposures to crystalline
silica dust (mainly cristobalite).
Estimated p ercen tages o f respirable
crystalline silica reported by
Checkoway et al. [1997] in mortality
study of same cohort: 10% for
calcined diatomaceous earth, and
20% for flux-calcined diatomaceous
earth.
27
28
mean duration of
Kreiss and Zhen [1996 ], 134 male residents of a ILO catego ry $1/0; 12.3% Prevalence Possible overestimation of silicosis
United S tates, hardrock mining town 27.6 yr for silicotics risk because of underestimation of
community-based who were aged $40: 100 and 22.9 yr for non- pre-1974 dust and silica exposures.
random sample survey silica-exposed hardrock silicotic miners; 41.6 yr Exposures were also estimated for
miners (includ ed 32 sili- for silicotics and 33.5 yr mines where there were no expo-
cosis cases) and 34 com- for nonsilicotics. sure data (17.1% of the person-yr of
munity controls without followup).
occupational dust expo-
sure. Risk estimates were presented for
mod els of cumulative silica dust
exposure or cum ulative dust
exposure the models of cumu-
lative silica dust exposure gave
higher estimates. Silicosis (i.e.,
$ category 1/1) risk estimates from
models of cumulative dust expo-
sure were similar to estimates for
South African gold miners [Hnizdo
and Sluis-Cremer 1993] and U.S.
gold miners [Steenland and Brown
1995a ].

mean duration of
Muir et al. [1989a,b], 2,10 9 current O ntario gold ILO catego ry $1/1 and 6.0% for gold Cumu lative risk Retired and former workers not
and uranium miners who small, rounded mine dust; 8.4% included, which may have under-

Verma et al. [1989],
Muir [1991]; Canada; started and worked $5 yr opacities (32 cases); for uranium mine estimated silicosis risk. Disagree-
retrospective cohort between 1940 and 1959 approximately 20 yr; dust. ment about silicosis classification
study and were followed to 1982 app roxim ately 25 yr among the five readers of the chest
or to the end of their dust (based on interpre- X-rays may have complicated the
exposure, whichever came tation of data in table analysis [Muir et al. 1989b].
first. and graph of Muir et al.
[1989b ]).
29
30
mean duration of
Ng and C han [1994], 338 current and previous ILO catego ry $1/1 27% Prevalence Cum ulative risks not calculated .
Hong Ko ng, cross- granite workers employed (rounded or irregular Exp osure data fo r 1976 198 1 in
sectional study $1 yr between 1967 and opacities); 17.4 yr; not one quarry and for 1971 1975 and
1985. reported. 1976 1981 in another quarry were
not available and w ere assumed to
be the same concentrations measured
in 1982 for the period 19761981
and in 1971 for the period 19711985
[Ng et al. 1987]. Possible under-
estimate of silicosis risk because
decedents were not included.

mean duration of
Rosenman et al. [1996], 549 current, 497 retired, ILO catego ry $1/0 and Not reported. Prevalence Prevalence of silicosis cases increased
United S tates, cross- and 26 current salaried rounde d opacities with (1) years of employme nt,

sectional study workers that were former (28 cases); 19.2 yr; (2) cigarette smoking, (3) mean
production workers in a 28.3 yr. silica exposure, and (4) cumulative
gray iron foundry that pro- silica exposure.
duced automotive engine
blocks (total Exposure estimates were derived
workers=1,072). from conversions of early silica
exposure data collected by impin-
gers. U nderascertainment of sili-
cosis cases is likely because there
was no systematic radio logic fol-
lowup of retired workers. Re sults
showed that African-American
workers had two times the risk of
radiographic silicosis compared
with white workers but a similar
duration of employment; however,
African-American workers had
greater mean exposure to silica dust.
W hen exposure to silica was
controlled for in the analysis, the
prevalence of rad iographic silico sis
was similar for African-American
workers and white workers.
31
32
mean duration of
Steenland and Brown 3,330 white male under- Mortality and ILO 13% [Zumwalde Cumu lative risk Silicosis risk estimates could have
[199 5a], Un ited States, ground gold miners em- category $1/1 (1976 et al. 1981] been affected by (1) combining
cohort study ployed $1 yr between radio graphic survey) silicosis deaths with silicosis cases
1940 and 1965 and or small opacities or detected by cross-sectional radio-
followed through 1990. large opacities (1960 graphic surveys, (2) d ifference in
radio graphic survey) quartz content of dust in early
(170 cases); 9 yr; 37 yr. years, (3) lack of dust measure-
ments before 1937.
*
International Labour Organization.

Median [Checkoway et al. 1997].

Molybdenum, lead, zinc, and gold mining.

Underlying or contributing cause of death was silicosis, silico-tuberculosis, respiratory tuberculosis, or pneumoconiosis.

A currently unpublished study of 600 retired 1995]. Although epidemiologic studies that
Vermont granite workers found nodular opaci- used cumulative exposure estimates represent
ties consistent with silicosis (degrees of profu- the best available source of information for
sion not reported in abstract) in 4.7% of 360 ra- characterizing the dose-response relationship
diographs read by three readers [Graham et al. in occupational cohorts, peak exposures may
1998]. The average duration of employment predict silicosis risk better than cumulative ex-
for these workers was 31 years, and the aver- posures [Checkoway and Rice 1992]. How-
age time from first exposure to radiographic ever, data on peak exposures are rarely avail-
examination was 39 years. Most workers in the able, and data supporting this hypothesis are
cohort were first employed after 1940, when limited.
average quartz dust concentrations were below
the current OSHA PEL [Graham et al. 1991; 3.3 TB and Other Infections
Ashe and Bergstrom 1964].
3.3.1 Definition
Although the variability in prevalence estimates
(i.e., 1% to 90%) cannot be solely attributed to As silicosis progresses, it may be complicated
differences in followup periods, chronic silico- by severe mycobacterial or fungal infections
sis is a progressive disease, and its development [NIOSH 1996b; Ziskind et al. 1976; Parkes
after a long latency period and after workers 1982; Parker 1994]. The most common of
leave employment must be accounted for in these infections, TB, occurs when the macro-
epidemiologic studies. A study of autopsied phages are overwhelmed by silica dust and are
gold miners in South Africa also supports the unable to kill the infectious organism Myco-
need for examining workers after a long la- bacterium tuberculosis [Parker 1994; Ng and
tency period and after they leave employment Chan 1991; NIOSH 1992a,b; Allison and Hart
[Hnizdo et al. 1993]. Radiologic findings for 1968]. About half of the mycobacterial infec-
profusion of rounded opacities (ILO category tions that occur in workers with exposure to sil-
$1/1) were compared with pathological find- ica are caused by M. tuberculosis, and the other
ings for silicosis in 326 miners with an average half are caused by the nontuberculous mycobac-
of 2.7 years between the radiologic and patho- teria (NTM) Mycobacterium kansasii and My-
logic examinations. Silicosis was not diag- cobacterium avium-intracellulare [Owens et
nosed radiographically for at least 61% of the al. 1988; NIOSH 1996b]. Infections in workers
miners with slight to marked silicosis at au- with silicosis may also be caused by Nocardia
topsy. The probability of a false negative read- asteroides and Cryptococcus [Ziskind et al.
ing increased with years of mining and average 1976; NIOSH 1996b; Parker 1994; Parker and
concentration of respirable dust [Hnizdo et al. Wagner 1998]. ATS [1997] recommends that
1993]. Experimental studies of rats also re- the diagnostic investigation of a patient with
ported a lack of complete agreement between silicosis and possible TB include consideration
histopathologic indicators of silica dust expo- of NTM disease. The ATS also recommends
sure and radiographic readings [Drew and that tuberculin tests be administered to persons
Kutzman 1984a,b]. with silicosis and to those without silicosis who
have at least 25 years of occupational exposure
to crystalline silica [ATS 1997].
In addition, improved exposure assessment
methods and data analyses that account for
3.3.2 Epidemiologic Studies
variations and deficiencies in exposure data
would improve the risk estimates for silica- Recent surveillance data indicate that TB rates
exposed workers [Agius et al. 1992; Checkoway in the United States are 5 to 10 times higher

among racial and ethnic minorities (after ad- 95% CI=8.6052.11); and for workers in oc-
justment for the effects of age, sex, and country cupations with high dust exposure (such as
of birth) [Cantwell et al. 1998]. Cantwell et al. drilling), the incidence was twice that of sur-
[1998] reported that the relative risk of TB in- face and maintenance workers (adjusted inci-
creased as socioeconomic status (measured by dence rate ratio=2.25; 95% CI=1.493.38)
six indicators) decreased, after adjustment for [Kleinschmidt and Churchyard 1997].
the effects of age (relative risks ranged from
2.6 to 5.6 in the lowest versus highest quartiles). Some evidence indicates that workers who do
The number of TB cases among foreign-born not have silicosis but who have had long ex-
persons in the United States increased by 56% posures to silica dust may be at increased risk
during the period 1986 to 1997 [CDC 1998c]. of developing TB. Two epidemiologic stud-
ies reported that, compared with the general
The association between TB and silicosis has population, a threefold incidence of TB cases
been firmly established by the results of occurred among 5,424 nonsilicotic, silica-
epidemiologic studies conducted during this exposed Danish foundry workers employed
century [Balmes 1990]. This association was 25 or more years [Sherson and Lander 1990],
supported by a survey of TB deaths among and nearly a tenfold incidence occurred among
silicotics in the United States for the period 335 nonsilicotic, black South African gold
1979 to 1991 [Althouse et al. 1995] and by the miners with a median underground employ-
results of four recent epidemiologic studies ment of 26 years [Cowie 1994].
[Goldsmith et al. 1995; Cowie 1994; Sherson
and Lander 1990; Kleinschmidt and Church- Westerholm et al. [1986] found 13 cases
yard 1997]. Black South African gold miners among 428 silicotic Swedish iron and steel
[Cowie 1994] and Danish foundry workers workers and 1 case in a comparison group of
[Sherson and Lander 1990] with chronic sili- 476 Swedish iron and steel workers with nor-
cosis had threefold and tenfold incidences of mal chest radiographs (level of statistical sig-
TB, respectively, compared with nonsilicotic, nificance not reported). Both groups had been
non-silica-exposed workers of similar age and exposed to silica for at least 5 years.
race. Goldsmith et al. [1995] compared the
mortality of 590 California silicosis claimants A study of TB incidence in 2,255 white South
with that of U.S. males and found that the TB African gold miners included 1,296 miners
mortality of the claimants was 50 times that of who had an autopsy [Hnizdo and Murray 1998,
all U.S. males (standardized mortality ratio 1999]. The smoking-adjusted relative risk for
[SMR]=56.35; 45 deaths observed, 0.8 expected; TB in miners without silicotic nodules on au-
95% confidence interval [CI]=41.1075.40). A topsy examination (n=577) increased slightly
retrospective study of TB among 4,976 miners with quartiles of cumulative dust exposure
from the Freegold mines in South Africa re- (relative risk=1.38 [95% CI=0.335.62] for the
ported that the incidence rate ratio for miners highest quartile of cumulative exposure). For
with silicosis (ILO category $1/1) was 1.54 miners without radiologically diagnosed sili-
(95% CI=1.002.37) compared with miners cosis (n=1,934), the smoking-adjusted relative
without silicosis (after adjusting for the ef- risk increased to 4.01 (95% CI=2.047.88) in
fects of age, followup period, cumulative the highest quartile of cumulative dust expo-
service, and occupation) [Kleinschmidt and sure [Hnizdo and Murray 1998, 1999]. The au-
Churchyard 1997]. The incidence of TB for thors defined radiologic silicosis as ILO cate-
the oldest age group was 21 times that of the gory $1/1. TB was diagnosed, on the average,
youngest group (incidence rate ratio=21.17; 7.6 years after the end of dust exposure and

6.8 years after the onset of radiological silico- operators, laborers, and mixing and blending
sisa result that supports the need for medical machine operators [CDC 1995].
surveillance of workers after the end of expo-
sure to silica dust [Hnizdo and Murray 1998]. Chen et al. [1997] conducted a case-control
Miners who developed TB before completing study (8,740 cases; 83,338 controls) with U.S.
10 years of underground employment were ex- National Occupational Mortality Surveillance
cluded because they were not allowed to con- (NOMS) data for 19831992. The study con-
tinue working underground after diagnosis. trolled for confounding from age, sex, race, so-
cioeconomic status, potential exposure to ac-
Corbett et al. [1999] conducted a recent case- tive TB, and the presence of silicosis and other
control study of TB and pulmonary disease pneumoconioses. The potential for silica expo-
caused by NTM in South African gold miners. sure was based on data from NOES [NIOSH
These researchers found that radiographic sili- 1988] and the National Occupational Health
cosis, focal radiological scarring, and human Survey of Mining (NOHSM) [NIOSH 1996c].
immunodeficiency virus (HIV) infection were This potential was categorized as high, in-
significant risk factors for NTM disease and termediate, or low or no. The study found
for TB. Past medical history of TB treatment that decedents with high potential for exposure
(odds ratio [OR]=15.1; 95% CI=7.6429.93) to silica and no documentation of silicosis on
and current employment in a dusty job at the the death certificate had a 30% greater odds of
mines (OR=2.5; 95% CI=1.464.44) were sig- mortality from respiratory TB than decedents
nificant risk factors for NTM. ORs for NTM with no potential exposure to silica after ad-
and TB increased with years of employment justment by logistic regression for the possi-
(range of ORs was 1.0 to 9.4 for NTM and 1.0 ble confounders mentioned earlier (OR=1.3;
to 4.1 for TB). The study included 206 NTM 95% CI=1.141.48). The results also suggest
patients and 381 TB patients of known HIV an exposure-response relationship between
status admitted to a South African hospital. silica exposure (in the absence of silicosis) and
Also included were 180 controls who were death from respiratory tuberculosis [Chen et al.
HIV-tested surgical or trauma patients admit- 1997].
ted to the same hospital during the same pe-
riod.
3.4 Cancer
Two recent studies about silica exposure and
3.4.1 Background
TB used U.S. occupational mortality data to
conduct a proportionate mortality study of per- The possible carcinogenicity of crystalline sil-
sons with TB by occupation for 1979 through ica dust became a subject of considerable and
1990 [CDC 1995; Chen et al. 1997]. Although intense debate in the scientific community in
the study design did not control for confound- the 1980s, especially after (1) publication of
ing, it identified six occupational groups with new information presented at a 1984 sympo-
potential exposure to silica dust that had sium in North Carolina [Goldsmith et al.
age-adjusted proportionate mortality ratios 1986], (2) epidemiologic studies by Wester-
(PMRs) for TB that were statistically signifi- holm [1980] and Finkelstein et al. [1982], and
cant (lower bound of the 95% CI>100) or (3) a literature review by Goldsmith et al.
greater than 200. Table 14 shows significant [1982] (see McDonald [1989, 1995] and Gra-
PMRs by race for construction occupations, ham [1998]). Many epidemiologic studies of
mining machine operators, grinding and pol- cancer mortality and morbidity in silica-
ishing machine operators, furnace and kiln exposed occupational groups were published

36
Table 14. Selected age-adjusted PMRs *, for pulmonary TB by usual occupation, sex, and race in 28 States, 19791990
M ale decedents Female deced ents
W hite Black W hite Black

Occupation of decedent
and 1980 census code Number PM R 95% CI Number PM R 95% CI Number PM R 95% CI Number PM R 95% CI
Construction occup ations 169 134 114156 105 128 104155 0 0

(553599, 865, and 869)
Brick and stone mason 12 213 110371 11 159 80285 0 0

(553 and 563564)
Carpenter (554, 567, and 50 147 109194 9 97 44184 0 0

569)
Roofer (595) 6 290 106630 1 53 1293 0 0
Construction laborer (869) 34 175 121244 61 156 120201 0 0
Mining machine operator 54 276 207360 4 128 35328 0 0

(616)
Grinding, abrad ing, 7 265 107547 1 94 2523 0 0

buffing, or polishing
machine operator (709)
Mixing or blending 1 58 2326 5 376 122878 0 0

machine operator (756)
Furnace, kiln, or oven 1 27 1153 5 206 67481 0 1 15,00 37282,842

operator, except food 0
(766)
Laborer, excep t 85 159 127196 92 111 89136 12 162 84283 8 147 64291
construction (889)
Source: Adapted from CDC [1995]. This data file includes death records from 28 States (Alaska, California, Colorado, Georgia, Idaho, Indiana, Kansas, Kentucky, Maine, Missouri,
Nebraska, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Carolina, Ohio, Oklahoma, Pennsylvania, Rhode Island, South Carolina, Tennessee, Utah, Vermont,
Washington, West Virginia, and Wisconsin).
*
Abbreviations: PMRs = proportionate mortality ratios; TB = tuberculosis; CI = confidence interval.

Selection criteria: (1) at least four TB deaths in race- and sex-specific group and (2) either a PMR >200 or a PMR with a 95% CI excluding 100.

later, but the issue remained unresolved. In In mixed environments such as ceramics,
October 1996, an IARC expert working group pottery, or brick manufacturing, where expo-
reviewed the published experimental and sure may be to two or more polymorphs of
epidemiologic studies of cancer in animals and crystalline silica, epidemiologic studies have
workers exposed to respirable crystalline sil- usually not identified specific exposures to
ica. The working group concluded that there is quartz or cristobalite. Therefore, excess lung
sufficient evidence in humans for the carcino- cancers that occurred in these environments
genicity of inhaled crystalline silica in the form cannot be associated with exposure to a given
of quartz or cristobalite from occupational polymorph but only with exposure to respira-
sources [IARC 1997]. In June 1996, the direc- ble crystalline silica. The epidemiologic stud-
tors of the ATS adopted an official statement ies of cancer have mainly investigated work-
of their Committee of the Scientific Assembly ers exposed to respirable crystalline silica in
on Environmental and Occupational Health. (1) ore mining, (2) quarrying and granite
This statement, prepared at the request of the works, (3) ceramics, pottery, glass, refractory
American Lung Association Occupational brick, and diatomaceous earth industries, or
Health Expert Advisory Group [ATS 1997], (4) foundries. The other major study group was
described the adverse health effects of expo- workers with silicosis, usually identified from
sure to crystalline silica, including lung cancer. national or local registries. Studies of workers
The ATS found the following: and silicotics that were not discussed in this
document because they failed to meet the
The available data support the conclu- least confounded criterion have been criti-
sion that silicosis produces increased cized for the following reasons [Checkoway
risk for bronchogenic carcinoma. 1995; McDonald 1995, 1996; Morgan and
Reger 1995; Weill and McDonald 1996; Sea-
However, less information is available ton 1995; Weill et al. 1994; Agius et al. 1992]:
for lung cancer risk among silicotics
who never smoked and workers who Inadequate, incomplete, or invalid expo-
were exposed to silica but did not have sure assessment
silicosis.
Potential selection and confounding bi-
Whether silica exposure is associated ases in the cohort studies of compen-
with lung cancer in the absence of silico- sated silicotics
sis is less clear.
Inadequate control of confounding from
cigarette smoking and from concurrent
NIOSH concurs with the conclusions of the
workplace exposures (e.g., potential ex-
IARC working group and the ATS. These con-
posure to radon progeny, arsenic, or die-
clusions agree with NIOSH testimony to
sel exhaust in ore mines and potential
OSHA, in which NIOSH recommended that
exposure to polycyclic aromatic hydro-
crystalline silica be considered a potentional
carbons in foundries)
occupational carcinogen [54 Fed. Reg. 2521
(1989)]. Inability to distinguish differences in
fibrogenic and carcinogenic potencies of
This section, like the IARC review, focuses on the various silica polymorphs
lung cancer and discusses the epidemiologic
studies that were the least likely to have results Lack of evidence of an exposure-
affected by confounding and selection biases. response relationship

3.4.2 Epidemiologic Studies Study results are often not uniform when a
of Lung Cancer large number of epidemiologic studies are re-
viewed and a variety of populations and work
Following a comprehensive review of the large environments are studied [IARC 1997]. In ad-
body of published epidemiologic studies, dition, IARC noted that the carcinogenicity of
IARC [1997] found that the following studies quartz or cristobalite may be dependent on in-
provide the least confounded investigations of herent characteristics of the crystalline silica or
an association between occupational exposure on external factors affecting its biological ac-
to crystalline silica and lung cancer: tivity or distribution of its polymorphs [IARC
1997].
1. U.S. gold miners [Steenland and Brown
1995b] Some of the least confounded studies reported
that lung cancer risk tended to increase with
2. Danish stone industry workers [Gunel
et al. 1989] C cumulative exposure to respirable silica
[i.e., Checkoway et al. 1993, 1996],
3. U.S. granite shed and quarry workers
[Costello and Graham 1988] C duration of exposure [i.e., Merlo et al.
1991; Partanen et al. 1994; Costello and
4. U.S. crushed stone industry workers Graham 1988; Costello et al. 1995;
[Costello et al. 1995] Dong et al. 1995],
5. U.S. diatomaceous earth industry workers C peak intensity of exposure [Burgess et

[Checkoway et al. 1993, 1996] al. 1997; Cherry et al. 1997; McDonald
et al. 1997],
6. Chinese refractory brick workers [Dong et al.
1995] C the presence of radiographically de-
fined silicosis [Amandus et al. 1992;
7. Italian refractory brick workers [Merlo et al. Dong et al.1995], and
1991; Puntoni et al. 1988]
C length of followup time from date of sil-
icosis diagnosis [Partanen et al. 1994]
8. U.K. pottery workers [McDonald et al.
(see Table 15).
1995,1997; Cherry et al. 1995,1997; Bur-
gess et al. 1997] These observed associations, including the
exposure-response associations, are unlikely
9. Chinese pottery workers [McLaughlin et al. to be explained by confounding or other biases.
1992] Thus overall, the epidemiologic studies sup-
port increased lung cancer risks from occupa-
10. Cohorts of registered silicotics from North tional exposure to inhaled crystalline silica
Carolina [Amandus et al. 1991,1992] and (i.e., quartz and cristobalite) [IARC 1997].
Finland [Kurppa et al. 1986; Partanen et al.
1994] 3.4.2.1 Updated or New Studies Since
the IARC Review
Although a few of these studies did not find a
statistically significant association between Two studies discussed in this section have re-
occupational exposure to crystalline silica and cently been updated: Checkoway et al. [1997,
lung cancer (Table 15), most of the studies did. 1999] updated their previous mortality studies

Table 15. IARC* -reviewed epidemiologic studies having the least confounded investigations of an association
between occupational exposure to crystalline silica and lung cancer
Smoking
Number of information
lung cancer ava ilable
Reference Study design, coho rt, deaths or Risk and
and country and followup Subgroup cases measure CI analyzed Com ments
Amandus et al. Mortality study of 714 Whites 33 2.6 1.83.6 Yes The age- and smoking-

[1991], United male, North Carolina adjusted rate ratio for
States dusty trades workers Nonwhites 1 0.7 Not reported white silicotics with lung
diagnosed with silicosis cancer was 3.9 (95% CI=
between 1940 and 1983 White silicotics: 2.46.4) compared with a
and compared with the Diagnosed while em- referent group of metal
19401983 lung cancer ployed 28 2.5 1.73.7 miners.
mortality rates for U.S.
males. Employed in jobs with Exposure to respirable
silica exposure silica dust was defined
only 26 2.3 1.53.4 as working in a dusty
trade and having radio-
Past or current smokers 18 3.4 2.05.3 graphic silicosis.
Silicotics, never smoked 5 1.7 0.53.9 No quantitative exposure

data were available.
Amandus et al. Mortality study of Silicotics 8 2.5 1.14.9 Yes Exposure to respirable
[1992], United subgroup of 306 white silica dust was defined
States males from Amandus Nonsilicotics** 2 1.0 0.13.5 as working in a dusty
et al. [1991] cohort of trade and having
silicotics diagnosed and Smokers: radiographic silicosis.
traced from 1940 Silicotics 5 3.4 1.17.9
through 1983. 143 of the Nonsilicotics** 1 1.3 0.037.1 No quantitative exposure
subgroup were data were available.
reclassified as silicotics,
and 96 were reclassified
as having a normal
radiograph. 10 deaths
from lung cancer
occurred in the
reclassified group.
39
40
Table 15 (Continued). IARC* -reviewed epidemiologic studies having the least confounded investigations of an association
Smoking
Burgess et al. Nested case-control Cumulative exposure to Yes ORs were adjusted for
[1997], study of lung cancer respirable crystalline smoking and radio-
Cherry et al. deaths within Cherry silica dust $4,000 :g/m3@yr 52 0.60 0.261.41 graphic changes.
[1997], et al. [1995], including
McDonald et al. duration and intensity of Duration of employment This was the only epi-
[1997], United exposure, smoking, and $ 20 yr 0.48 0.211.09 demiologic study of peak
Kingdom radiological changes. exposure effects and lung
Cases were employed as Mean intensity of silica cancer. Results support
pottery workers for dust exposure $ 200 : g/m3 1.68 0.933.03 significant lung cancer
$ 10 yr. Each death was risk for high-intensity
matched with 3 or 4 Maximum silica dust silica exposures.
controls on date of birth exposure $ 400 : g/m3 2.07 1.044.14
and date of first expo- Silica dust exposures
sure. $ 400 : g/m3 occurred in
firing and post-firing
operations. Exposures to
cristobalite were possible.

Smoking

Checkoway et al. Mortality study of 2,570 59 1.43 1.091.84 Limited to Estimated relative risks
[1993; 1996], male workers at comparisons for lung cancer (not
United States diatomaceous earth of smoking shown) were adjusted for
plants employed $ 1 yr prevalence. age, calendar year, dura-
and worked $ 1 day tion of followup, and
between 1942 and 1987. ethnicity. The risks in-
Cohort mortality traced creased significantly
for that period. (P# 0.05 for trend) with
duration of employment
Checkoway et al. [1996] 52 1.41 1.051.85 and cumulative exposure
reanalyzed 2,266 work- to crystalline silica
ers (a subset of the orig- [Checkoway et al. 1993].
inal cohort). Mortality Checkoway et al. [1996]
traced from 1942 also adjusted for asbestos
through 1987. exposure.
Cherry et al. Mortality study of 5,115 68 1.28 1.041.57 No Lung cancer rates in pot-
[1995], United pottery workers, ex- tery workers were com-
Kingdom cluding exposure to pared with local mor-
asbestos, foundry, and tality rates.
other dusts; with
mortality followup to
June 30, 1992.
41
42
Smoking
Costello and Mortality study of 5,414 Quarry workers 20 0.82 Not reported No Dust exposure data were
Graham [1988], white male workers in not included, limiting
United States Vermont granite sheds Shed workers: 98 1.27 Not reported conclusions about
and quarries employed Started before 1940, exposure-response.
between 1950 and 1982 latency period $40 yr, Cohort overlaps with
with at least one radio- tenure $ 30 yr 47 1.81 1.332.41*** cohort of Davis et al.
logic examination in the Started after 1940, [1983].
worker surveillance latency period $25 yr, 1.012.77
program. tenure $ 10 yr 17 1.73 CIs reported by IARC
[1997].
Costello et al. Mortality study of 3,246 Whites 40 1.2 0.91.6 No

[1995], male workers employed
United States $ 1 yr between 1940 and Nonwhites 11 1.9 0.93.3
1980 at 20 U.S. crushed
stone (i.e., granite, lime- Workers in granite
stone, traprock, or sand- facilities with $ 20-yr
stone) operations. latency period and
$ 10-yr tenure 7 3.5 1.47.3
Workers in limestone
facilities 23 1.5 1.02.3
Workers in traprock
facilities 3 0.6 0.11.8

Smoking
Dong et al. Mortality study of lung Silicotics 35 2.1 Not reported*** Yes Twofold excess lung

[1995], China cancer in 6,266 male cancer mortality occurred
silicotic and nonsilicotic Silicotics in Chinese in both smokers and
refractory brick workers radiological category: nonsmokers. Exposure-
employed before 1962 I 21 2.0 Not reported*** response trends were
and followed for mor- found for years since first
tality from 1963 to II 10 2.3 Not reported employment and lung
1985. 11,470 cancer mortality, and for
nonsilicotic male steel III 4 2.6 Not reported severity of silicosis and
workers used as lung cancer mortality.
controls. Nonsilicotics 30 1.1 Not reported***
Gunel et al. Cohort study of 2,175 Lung cancer cases 44 2.00 1.492.69 Yes Adjusted for regional
[1989], Denmark Danish stone workers differences in smoking.
who met the following Lung cancer mortality
criteria: highest among Copen-
were alive on Jan. 1, hagen sandstone cutters
1943, or were born hired before 1940 prior to
later, and ventilation improve-
were aged <65 when ments.
first identified in one
of 6 data sources.
The cohort included
2,071 cancer cases
identified in the Danish
cancer registry between
1943 and 1984.
43
44
Smoking
and country and followup Subgroup cases measure * CI analyzed Com ments
McDonald et al. Preliminary report of Lung cancer deaths in No Preliminary results

[1995], proportionate mortality pottery workers not (final results in Cherry
United Kingdom study of 7,020 pottery exposed to asbestos 112 1.22 1.041.43 et al. [1995]).
workers born between
1916 and 1945 with Smokers and nonsmokers Lung cancer rates in pot-
mortality followup to with $ 10 yr of silica ex- tery workers were com-
June 30, 1992. Prelim- posure 75 1.4 0.72.7 pared with local mor-
inary nested case-control tality rates.
study of 75 lung cancer Smokers with $ 10 yr of
cases and 75 controls. silica exposure 47 2.8 1.17.5
McLaughlin Nested case-control Cumulative respirable Yes ORs were adjusted for
et al. [1992], study of 62 pottery fac- silica dust exposure age and smoking. Test for
China tory workers employed (: g/m3@yr): exposure-response trend
between 1972 and 1974 None 11 1.0 was not statistically
who died from lung can- Low (0.18.69) 17 1.8 1.042.87 significant (P>0.05) for
cer before 1990; Medium (8.7026.2) 27 1.5 0.992.18 cumulative exposure to
238 controls matched by High ($ 26.3) 7 2.1 0.804.12 dust or respirable silica.
decade of birth and fac- High OR (7.4; CI and
tory. number of deaths not
reported) for lung cancer
in workers who smoked
>20 cigarettes per day.
CIs reported in IARC
monograph [1997].

Smoking
Merlo et al. 1,022 male refractory All brick workers 28 1.51 1.002.18 Yes Smoking habits of cohort

[1991], Italy brick workers employed comparable with the
at least 6 months Brick workers: national population
between 1954 and 1977. # 19 yr since 1st (includes the men in
Retrospective cohort exposure and Puntoni et al. [1988]).
study of mortality employed # 19 yr 7 1.05 0.422.16
through 1986. >19 yr since 1st
exposure and
employed # 19 yr 8 1.75 0.753.46
>19 yr since 1st
exposure and
employed >19 yr 13 2.01 1.073.44
45
46
Smoking
Partanen et al. Cohort study of 811 Length of followup from Yes Update of Kurppa et al.
[1994], male silicotics, compen- date of silicosis diagnosis: [1986].
Finland sated and not compen- <2 yr 1 0.4 0.012.3
sated, who were diag- 29 yr 32 2.7 1.93.9 No evidence of con-
nosed between 1936 and $ 10 yr 168 3.3 2.54.1 founding by tobacco
1977 in Finland. Cancer smoking.
incidence for Histology of lung cancers:
19531991 was Adenocarcinoma 5 2.0 0.64.6
obtained from the Squamous-cell 34 3.2 2.34.5
Finnish Cancer Registry. Small-cell 9 2.1 0.93.9
Other/unknown 53 3.0 2.23.9
Industry:
Mining/quarrying 38 3.7 2.65.0
(excluding granite)
Granite 13 2.9 1.65.0
Glass/ceramic 10 3.3 1.66.1
Grinding/sharpening 3 3.0 .68.7
Casting/founding 22 1.8 1.12.6
Construction 2 10 1.337
Excavation/foundation 9 5.8 2.711.1

Smoking
Steenland and Cohort study of 3,328 115 1.13 0.941.36 Yes High historical expo-

Brown [1995b], white male gold miners sures. No exposure-
United States employed underground response trend by cumu-
$ 1 yr between 1940 and lative dust exposure.
1965 and followed for
mortality from 1977 to Low radon and arsenic
1990. Mortality rates of exposures.
U.S. males used for
comparison.
Source: IARC [1997].
*
Abbreviations: CI=confidence interval; IARC=International Agency for Research on Cancer; PMR=proportional mortality ratio; OR=odds ratio; SIR=standardized incidence
ratio; SMR=standardized mortality ratio; SRR=standardized rate ratio

SMR unless otherwise noted.

95% CI unless otherwise noted.

Workers who had no known exposure to other occupational carcinogens such as asbestos manufacturing, insulation work, olivine mining, talc, and foundry work.
**
Nonsilicotics are subjects with normal radiographs.

OR.

90% CI.

P <0.05.
***
P <0.01.

Values in this study are SRRs.

Values in this study are SIRs.

PMR.
47
of diatomaceous earth workers [Checkoway adjustment for smoking and inclusion of a 20-,
et al. 1993, 1996] by including deaths after 10-, or 0-year lag period, mean respirable silica
1987 and through 1994, and by analyzing lung concentration (i.e., estimated daily 8-hr TWA
cancer risk among workers with radiographic airborne concentrations in g/m3) was associ-
silicosis. Lung cancer mortality risk was ated with lung cancer (P<0.008 for each lag
highest in the highest category of cumulative period):
exposure to respirable crystalline silica (rate
ratio with no exposure lag period=2.11; 95% Lag OR 95% CI
CI=1.074.1; rate ratio for 15-year exposure
lag period=1.05; 95% CI=0.991.11). The rate 20 yr 1.60 1.112.31
ratios were adjusted for the effects of age, cal- 10 yr 1.66 1.142.41
endar year, duration of followup, and ethnicity. 0 yr 1.67 1.132.47
Among workers with radiological silicosis
(ILO category $1/0 or large opacity; n=81), However, exposure duration and cumulative
the lung cancer SMR was 1.57 (95% CI= silica dust exposure were not significantly as-
0.434.03) [Checkoway et al. 1999]. For work- sociated with lung cancer mortality, regardless
ers without silicosis (ILO category <1/0), the of lag time [Cherry et al. 1998]. The presence
SMR was 1.19 (95% CI=0.871.57). The of small, parenchymal radiographic opacities
SMRs were adjusted for age and calendar year (ILO category $1/0) was not related to lung
and were based on the expected number of cancer mortality before adjustment for smok-
deaths for white U.S. males. For the nonsilico- ing (P=0.78) or after adjustment for smoking
tic workers, a statistically significant, positive and mean silica concentration (P=0.68). The
dose-response relationship (P=0.02) was ob- authors concluded that crystalline silica may
served between SMRs for lung cancer and cat- well be a human carcinogen [Cherry et al.
egory of cumulative respirable silica exposure. 1998].
The SMRs ranged from 1.05 in the lowest ex-
posure category (<0.5 mg/m3@ year, 13 deaths, Other studies published since the IARC review
95% CI=0.561.79) to 2.40 in the highest ex- also investigated exposure-response associa-
posure category ($5.0 mg/m3 @ year; 12 deaths, tions for lung cancer and exposure to crystal-
95% CI=1.244.20). For the 81 workers with line silica. Rafnsson and Gunnarsdttir [1997]
radiographic silicosis, an SMR >1.0 was ob- reported that the incidence of lung cancer cases
served only in the highest exposure category among 1,346 diatomaceous earth workers in
(i.e., $5.0 mg/m3 @ year) (4 deaths observed; Iceland was not statistically significant for
SMR=2.94; 95% CI=0.807.53). These results workers who had 9 years before start of
suggest that silicosis may not be a necessary followup and who were employed $5 years
condition for silica-related lung cancer. How- (standardized incidence ratio [SIR] based on
ever, radiographic surveillance of this cohort 3 cases observed=2.70; 95% CI=0.567.90) or
did not extend beyond the dates of employ- employed #5 years (SIR based on 2 cases ob-
ment termination, and autopsies were not rou- served=1.19; 95% CI=0.144.30).
tinely conducted [Checkoway et al. 1999].
de Klerk and Musk [1998] conducted a cohort
Cherry et al. [1998] finalized the preliminary study of 2,297 surface and underground gold
results of a nested case-control study of 52 miners in western Australia who participated
lung cancer deaths in 5,115 pottery workers in surveys of respiratory symptoms, smoking
(see Burgess et al. [1997], Cherry et al. [1997], habits, and lung function in 1961, 1974, and
and McDonald et al. [1997] in Table 15). After 1975. Eighty-nine percent of the cohort was

traced to the end of 1993 for trachea, bronchus, pyrite (1%4%), and heavy minerals with
and lung cancer mortality and incidence of grains of gold and uranium-bearing minerals
compensated silicosis (i.e., compensation (2%4%). Seventy-eight miners who died
awarded by the Pneumoconiosis Medical from lung cancer (69 of the 78 had a necropsy)
Board). A nested case-control analysis of the during 19701986 were matched by year of
138 lung cancer deaths found that lung cancer birth with 386 control subjects from the same
mortality was related to log total cumulative cohort [Hnizdo et al. 1997]. Conditional logis-
silica dust exposure after adjustment for tic regression models were used to analyze the
smoking (cigarette, pipe, or cigar) and for the relationship of lung cancer mortality with ciga-
presence of bronchitis at survey (relative rette smoking (pack-years), cumulative dust
rate=1.31; 95% CI=1.011.70). However, the exposure (mg/m3 @ year), years of underground
effect of cumulative silica dust exposure on mining, incidence of radiographic silicosis
lung cancer mortality was not significant after (ILO category $1/1 diagnosed up to 3 years be-
adjustment for smoking, bronchitis, and com- fore death of a matched case), and uranium
pensation for silicosis (relative rate=1.20; production or uranium grade of the ore in the
95% CI=0.921.56). Other silica exposure gold mine. Radon progeny measurements in
variables (i.e., duration of underground or the gold mines were not available.
surface employment and intensity of under-
ground or surface exposure) were not signifi-
Lung cancer mortality was associated with cig-
cantly related to lung cancer mortality
arette smoking, cumulative dust exposure (lag
(P>0.15) after adjustment for smoking and
time was 20 years from death), duration of un-
bronchitis. Cigarette smoking (relative rate=32.5;
derground mining (lag time was 20 years from
95% CI=4.4241.2 for $25 cigarettes smoked
death), and silicosis. The best-fitting model
per day), incidence of a compensation award
predicted relative risks of 2.45 (95% CI=
for silicosis after lung cancer diagnosis (relative
1.25.2) for silicosis and the following relative
rate=1.59; 95% CI=1.102.28), and presence
risks for various pack-years of smoking:
of bronchitis at survey (relative rate=1.60;
95% CI=1.092.33) were significantly related
to lung cancer mortality [de Klerk and Musk
1998]. The results of this study do not support a Pack-years 95% CI Relative risk
relationship between lung cancer and silica ex- <6.5 1
posure in the absence of silicosis (i.e., a com- 6.520 0.716.8 3.5
pensation award for silicosis after lung cancer 2130 1.325.8 5.7
diagnosis). However, controlling for silicosis >30 3.156.2 13 .2
compensation and bronchitis may have
masked a silica effect because both are markers
of silica exposure. The authors stated that variables representing
uranium mining were not significantly related
to lung cancer mortality (modeling results for
Hnizdo et al. [1997] conducted a nested these variables were not presented) [Hnizdo et
case-control study of lung cancer deaths in a al. 1997]. The authors proposed three explana-
cohort of 2,260 white South African under- tions for their results:
ground gold miners. (A lung cancer mortality
cohort study had been conducted earlier
[Hnizdo and Sluis-Cremer 1991]). The mineral Miners with high dust exposure who de-
content of the rock in the gold mines was mostly velop silicosis have increased lung can-
quartz (70%90%), silicates (10%30%), cer risk.

High silica dust exposure concentrations of silica-exposed workers was 1.3 (95% CI=
are important in the pathogenesis of lung 1.21.4)a moderate and statistically signifi-
cancer, and silicosis is coincidental. cant relative risk estimate [Steenland and
Stayner 1997]. Eight of the 16 studies con-
High silica dust exposure concentrations trolled for the effects of smoking, either di-
are a surrogate measure of exposure to rectly or indirectly.
radon progeny [Hnizdo et al. 1997].
Another meta-analysis of 23 lung cancer stud-
ies of silicotics (including 14 of the studies an-
3.4.2.2 Lung Cancer Meta-Analyses
alyzed by Steenland and Stayner [1997]) re-
Meta-analysis and other systematic literature ported a pooled risk estimate of 2.2 (95% CI=
review methods are useful tools for sum- 2.12.4) [Smith et al. 1995]. The statistically
marizing exposure risk estimates from a large significant pooled risk estimates from both
amount of information [Mulrow 1994]. Meta- meta-analyses strongly support an association
analyses or summary reviews of epidemiologic between silicosis and lung cancer. The in-
studies of silicotics with lung cancer have been creased risk of lung cancer for silicotics is also
conducted by investigators in the United States supported by the following [IARC 1997]:
[Steenland and Stayner 1997; Smith et al.
1995] and Japan [Tsuda et al. 1997]. IARC is 1. The magnitude of the risk estimates (i.e.,
performing a pooled analysis of epidemiologic most studies reported risks greater than 2.0
data from several cohorts to investigate lung for silicotics after adjusting for the effects
cancer risks in nonsilicotic workers.
of cigarette smokingcompared with ex-
posed nonsilicotics or the general popula-
Steenland and Stayner [1997] and IARC
tion)
[1997] found that the majority of studies of
silicotics reported statistically significant ex-
cess lung cancer risks across different coun- 2. The observation of exposure-response gra-
tries, industries, and time periods while con- dients with various indicators of exposure
trolling for the effects of cigarette smoking
[Steenland and Stayner 1997; IARC 1997]. 3. Consistent findings of excess risk in differ-
Exposure-response gradients were also ob- ent countries, industries, and time periods
served. The summary relative risk was 2.3
(95% CI=2.22.6) for 19 cohort and case- 4. Two studies that provided reasonable evi-
control studies of silicoticsexcluding studies dence for an unconfounded association
of miners and foundry workers because of (i.e., Amandus et al. [1991, 1992, 1995]
potential exposure to other carcinogens, and and Partanen et al. [1994], an update of
omitting autopsy studies and proportionate Kurppa et al. [1986])
mortality studies because of possible selection
biases [Steenland and Stayner 1997]. Fifteen Tsuda et al. [1997] conducted a lung cancer
of the 19 studies directly or indirectly controlled meta-analysis of pneumoconiosis or silicosis
for the effects of smoking. The summary rela- studies (excluding asbestosis). Lung cancer
tive risk of 16 cohort* and case-control studies risk estimates were pooled from 32 mortality
studies published from 1980 to 1994. The esti-
mated rate ratios were similar to those reported
by Steenland and Stayner [1997] and Smith et
*
Cohort size ranged from 969 to 6,266 workers. al. [1995]:

Rate ratio 95% CI For workers who may have been exposed to
All studies (32) . . . . . . 2.74 2.602.90
crystalline silica, there have been infrequent
Cohort studies only reports of statistically significant excesses of
(25 of 32) . . . . . . . . 2.77 2.612.94 deaths or cases of other cancers such as naso-
Case-control studies pharyngeal or pharyngeal cancer [Chen et al.
(5 of 32). . . . . . . . . 2.84 2.253.59 1992; Carta et al. 1991], salivary gland cancer
[Zheng et al. 1996], liver cancer [Chen et al.
1992; Hua et al. 1992], bone cancer [Forastiere
3.4.3 Other Cancers
et al. 1989; Steenland and Beaumont 1986],
Mortality studies of workers have reported sta- pancreatic cancer [Kauppinen et al. 1995], skin
tistically significant excesses of deaths from cancer [Partanen et al. 1994; Rafnsson and
stomach or gastric cancer in iron ore miners Gunnarsdttir 1997], esophageal cancer [Pan
[St. Clair Renard 1984; Lawler et al. 1985; Mur et al. 1999; Xu et al. 1996; Belli et al. 1989],
et al. 1987], Canadian gold miners [Muller et cancers of the digestive system [Decoufle and
al. 1983; Shannon et al. 1987; Miller et al. Wood 1979], intestinal or peritoneal cancer
1987; Kusiak et al. 1993b], lead and zinc min- [Amandus et al. 1991; Goldsmith et al. 1995;
ers [Belli et al. 1989], brick production work- Costello et al. 1995], lymphopoietic or hema-
ers [Katsnelson and Mokronosova 1979], topoietic cancers [Redmond et al. 1981; Silver-
foundry and other metal workers [Neuberger stein et al. 1986; Steenland and Brown 1995b],
and Kundi 1990], jewelry workers [Hayes et al. brain cancer [Rafnsson and Gunnarsdttir
1993; Dubrow and Gute 1987; Sparks and 1997], and bladder cancer [Bravo et al. 1987].
Wegman 1980], farmers (reviewed by Blair Again, an association has not been established
and Zahm [1991]), and farm workers [Stubbs between these cancers and exposure to crystal-
et al. 1984] (reviewed by Zahm and Blair line silica.
[1993]). A recent case-control study of 250
male hospital patients in Canada found a sta-
tistically significant excess of pathologically
confirmed stomach cancer among the 25 pa- 3.5 Other Nonmalignant
tients who reported a history of substantial Respiratory Diseases and
occupational exposure to crystalline silica Related Conditions
compared with 2,822 controls (OR=1.7; 95%
CI=1.12.7 after adjusting for the effects of 3.5.1 COPD
age, birthplace, education, and cigarette smok-
ing) [Parent et al. 1998]. However, in a review 3.5.1.1 Definition
of epidemiologic studies of gastric cancer and
COPD describes chronic airflow limitation
dusty occupations, Cocco et al. [1996] noted
that is usually irreversible [ATS 1987; Beck-
that because most studies did not adjust for
lake 1992; Snider 1989]. COPD includes four
the effects of confounding factors or assess a
interrelated disease processes: chronic bron-
dose-response relationship, evidence was in-
chitis, emphysema, asthma [Barnhart 1994;
sufficient to conclude that silica is a gastric
Snider 1989], and peripheral airways disease
carcinogen.
[ATS 1987]. Cigarette smoking is a major
cause of COPD, but community air pollution
and occupational exposure to dust, particularly
Two of the studies are proportionate mortality studies among smokers, also contribute to COPD
for which rate ratios were not reported. [Becklake 1992].

3.5.1.2 Epidemiologic Studies workers exposed to coal dust, asbestos, or dust

that contained crystalline silica [Barnhart
Although thousands of studies have been pub- 1994]. However, cigarette smoking is also as-
lished about occupational exposure to nonor- sociated with chronic bronchitis and must be
ganic dusts and COPD, only 13 studies of 4 co- considered when investigating the relationship
horts of silica-exposed workers met rigorous between occupational exposures and bron-
methodologic criteria for a review conducted chitic symptoms [Barnhart 1994; ATS 1997].
by Oxman et al. [1993]. Three of the cohorts
were coal miners and one was South African 3.5.3.2 Epidemiologic Studies
gold miners. According to Oxman et al. [1993],
the studies provided evidence that exposure to Statistically significant (P<0.05) relationships
gold mine dust is an important cause of COPD, independent of smoking were found between
particularly in smokers, and that the risk of exposure to gold mine dust and chronic
COPD appeared to be greater for gold miners bronchitis or chronic sputum production in
than for coal miners. cross-sectional studies of gold miners in
South Africa [Wiles and Faure 1977; Cowie
and Mabena 1991] and Australia [Holman et
3.5.2 Asthma al. 1987]. However, no statistically signifi-
cant relationships independent of smoking
Crystalline silica has not been identified as an oc- were found between exposure and chronic
cupational asthma-inducing agent [Chan-Yeung bronchitis or bronchitic symptoms in cross-
1994], and no published epidemiologic studies sectional studies of molybdenum miners
have specifically investigated whether asthma is [Kreiss et al. 1989b], uranium miners
related to crystalline silica dust exposure. [Samet et al. 1984], taconite miners [Clark
et al. 1980], Indian agate grinders and chip-
3.5.3 Chronic Bronchitis pers [Rastogi et al. 1991], and a population-
based study of South African gold miners
3.5.3.1 Definition [Sluis-Cremer et al. 1967] (Table 16).
Chronic bronchitis is clinically defined as the Wiles and Hnizdo [1991] studied the relation-
occurrence of chronic or recurrent bronchial ship between mortality, airflow obstruction,
hypersecretion (i.e., a productive cough) on and mucus hypersecretion in 2,065 South Afri-
most days of the week for at least 3 months of can gold miners. They found that after stan-
2 sequential years [ATS 1987, 1995; Barnhart dardization for airways obstruction, mucus
1994]. The excess mucus secretion should not hypersecretion was not related to mortality
be related to a disease such as TB [ATS 1987, from COPD (54 deaths). However, mucus
1995]. Chronic bronchitis has been associated hypersecretion remained significantly related
with both airflow obstruction and abnormali- to mortality from ischemic heart disease and
ties in gas exchange [Barnhart 1994]. Although all causes of death, even after adjustment for
the terms industrial bronchitis and occupa- years of cigarette smoking and particle-years
tional bronchitis traditionally refer to chronic of exposure to gold mine dust [Wiles and
bronchitis that is associated with occupational Hnizdo 1991].
exposure, bronchitic symptoms may also occur
after occupational exposures that are acute or
that last less than 2 years. An association be-
tween reduced ventilatory function and bron-
Cumulative exposure, duration of exposure, or inten-
chitic symptoms has been reported in studies of sity of exposure.

Table 16. Epidemiologic studies of bronchitis in workers exposed to silica dust
Study design, Bronchitis Risk Adjusted

Reference cohort, and cases in measure for
and country followup Subgroup subgroup* (OR ) 95% CI smoking Com ments
Clark et al. Cross-sectional study 80 dust-exposed smokers with Yes Note that subgroups represent
[1980], United of bronchitic symp- cough all day 24% bronchitic symptomsnot cases.
States toms in 249 white 33 controls were employees of a
male taconite miners; 52 dust-exposed nonsmokers school; however, occupations of

mean age was 49 with with cough all day 1% the other controls were not re-
$ 20 yr of exposure ported. Occupational dust expo-
to taconite dust. 24 nondust-exposed nonsmokers sures to the control group may
Control group of with cough all day 1% have contributed to the similar or
86 men with no his- higher prevalences of bronchitic
tory of exposure to 32 nondust-exposed smokers symptoms in that group.
taconite mine dust. with cough all day 16%
80 dust-exposed smokers with

phlegm all day 18%
24 nondust-exposed nonsmokers
with phlegm all day 1%
32 nondust-exposed smokers
with phlegm all day 37%
53
54
Table 16 (Continued). Epidemiologic studies of bronchitis in workers exposed to silica dust
Study design, Bronc hitis Risk Adjusted

Cowie and Cross-sectional study Miners with chronic sputum pro- Yes 62% of miners who smoked and
Mabena [1991], of 1,197 black, male duction and high dust exposure 1.8 1.192.69 45% of miners who never smoked
South Africa underground gold had chronic bronchitic symptom
miners aged 2876 complex.
with 25.1 yr since Miners with 24 pack-yr of smok-
first exposure (mean). ing exposure and chronic sputum High and low dust exposure
857 miners had production 3.7 2.625.23** categories were based on quali-
chronic silicosis. tative assessments of underground
mine dust exposure and occupa-
tion.
Authors stated that bronchitic

symptoms may also have been re-
lated to underground mining expo-
sures other than respirable quartz
dust.


Holman et al. Cross-sectional study Total cohort 14% Yes ORs were based on comparison
[1987], of 1,363 male, cur- with nonminers and were adjusted
Australia rent gold miners Miners with chronic bronchitis: for effects of smoking and age.
(51% were under- 19 yr of underground gold

ground miners) aged mining 1.8 1.03.3
20 to >60. 53% of
the cohort worked 1019 yr of underground gold
underground 119 yr. mining 2.5 1.25.2
$ 20 yr of underground gold
mining 5.1 2.410.9
Kreiss et al. Community-based Underground miners with >10 yr Yes ORs were based on comparison
[1989b], United cross-sectional study of employment: with residents having no history of
States of 389 male residents With chronic cough 0.84 0.371.90 occupational dust exposure.
of Leadville, CO.
281 (72.2%) of the With chronic phlegm 0.93 0.422.06 Nearly half (49%) of personal
sample had worked samples for quartz exposures
at the local molyb- among the miners exceeded the
denum mine. Mean NIOSH REL of 0.05 mg/m3 (total
yr of exposure: 9.3. number of samples was not
Mean age of cohort: reported).
44.
55
56
Study design, Bronc hitis Risk Adjusted

Ng et al. Cross-sectional study Quarry workers with high dust Yes No quantitative exposure concen-
[1992b], of 85 granite quarry exposure: trations for dust or silica were re-
Singapore workers with high All (85) 9 ported: granite quarry rock dril-
dust exposure and Nonsmokers (34) 2 lers and rock crushers were as-
154 quarry workers Ex-smokers (5) sumed to have "high" silica expo-
with low dust ex- Current smokers (46) 7 sure; and administrative workers,
posure (see com- truck drivers, vehicle maintenance
ments); mean age workers, and loader operators were
was 42. Mean dur- assumed to have "low" silica expo-
ation of employment sure.
was 13.7 yr. Com-
parison group of Results were adjusted for effects of
148 male postal age.
workers with no ex-
posure to granite
dust; mean age was
40.


Rastogi et al. Cross-sectional study Chronic bronchitis: Yes Association between dust exposure
[1991], India of 240 male and Male: and chronic bronchitis may not
102 female agate Agate workers 3.75/100 have been detected because the
grinders and chip- Controls 4.58/100 control group included workers

pers, and 116 male Female: who may have occupational expo-
and 33 female con- Agate workers 0 sure to respirable silica dust (e.g.,
trols with nondusty Controls 9.1/100 rickshaw-pullers and sweepers).
occupations. The High prevalence of tuberculosis in
mean duration of Acute bronchitis: agate workers and controls may
exposure was 10 yr Male: have masked an association for
for males and 8.9 yr Agate workers 9.1/100 bronchitis.
for females. Controls 5.17/100
Female:
Agate workers 9.8/100 P<0.05
Controls 0
Samet et al. Cross-sectional study Miners with chronic cough: Yes Chronic cough and chronic
[1984], United of 192 male, current 1019 yr of mining 14.1/100*** phlegm were not associated with
States underground urani- $ 20 yr of mining 22.7/100*** duration of silica exposure in
um miners aged <40, multiple logistic regression
4059, and $ 60. Miners with chronic phlegm: analysis (results were not
145 miners (76%) 1019 yr of mining 31.9/100*** reported).
mined $ 10 yr under- $ 20 yr of mining 36.6/100***
ground.
57
58

Sluis-Cremer Community-based, Residents w/chronic bronchitis: Yes Dust-exposed was defined as

et al. [1967], cross-sectional study Dust-exposed: self-reported occupational expo-
South Africa of chronic bronchitis Smokers 199/394 (51%) sure in a scheduled dusty area of
in 827 male residents Nonsmokers 22/168 (13%) a mine.
who were aged >35 Nondust-exposed:
and who lived in Smokers 45/161 (28%) A significant difference existed be-
Carletonville, a Nonsmokers and ex-smokers 7/104 (7%) tween the prevalence of chronic
South African town bronchitis in dust-exposed smok-
with four gold mines. ers and nondust-exposed smokers
(P<0.01).
No significant difference existed

between dust-exposed and
nondust-exposed nonsmokers or
ex-smokers.
Wiles and Cross-sectional study 138 miners in highest cumulative Yes Prevalence of chronic bronchitis
Faure [1977], of chronic bronchitis dust exposure group: increased with increasing mean
South Africa in 2,209 under- Nonsmokers 2/14 (14%) dust concentration (P<0.001) and
ground gold miners Ex-smokers 4/31 (13%) with cumulative dust exposure in
(race not reported) Smokers 47/93 (51%) nonsmokers (P<0.05), ex-smokers
aged 4554 with (P<0.05), and smokers (P<0.001).
$ 10 yr of employ-
ment. 653 were ex-
miners for $ 1 yr.
*
Number of cases unless otherwise indicated.

Abbreviations: CI=confidence interval; NIOSH=National Institute for Occupational Safety and Health; OR=odds ratio; REL=recommended exposure limit.

Dash indicates not reported.

Compared with miners having low dust exposure.
**
Compared with miners having 0 pack-yr.

Estimated prevalence.

Risk measure was not reported, but P<0.01 compared with controls.

Risk measure was not reported, but P>0.05 compared with controls.
***
Standardized to the overall distribution of cigarette smoking.

A mortality study of workers in dusty trades the clinical evaluation of workers with occupa-
reported a statistically significant number of tional lung diseases. Nonoccupational factors
deaths from bronchitis when compared with (e.g., the subjects age, height, racial group,
mortality rates for other white males in the and smoking habit) as well as the quality and
United States (P<0.05; 6 deaths observed; interpretation of the spirometric testing can in-
0.8 deaths expected) [Amandus et al. 1991]. fluence pulmonary function test results [Parkes
1982; Rosenstock 1994; Crapo 1994]. In gen-
The discrepancies among the cross-sectional eral, an FEV1 loss of about 20 to 30 ml/year in
studies of bronchitis in quartz-exposed popu- nonsmokers or >60 ml/year in smokers [Crapo
lations may be attributable to the presence or 1994] may suggest a decline greater than ex-
absence of concurrent exposures among the pected. Wagner [1994] suggests further clini-
cohorts that have been studied [Kreiss et al. cal evaluation of workers with a 15% decrease
1989b]. Particle size is another factor that from the baseline percentage of predicted
may have affected the results. The dust in value for FEV1 or FVC (e.g., from 105% to
one work environment may have had a 90% of the predicted FEV1).
higher proportion of particles that were not
of respirable size compared with dust in an-
other work environment. Larger-sized dust Loss of FEV1 has been associated with an in-
particles may be responsible for large-airways creased risk of death from various diseases,
diseases such as chronic bronchitis, whereas including COPD [Crapo 1994; Tockman and
respirable dust particles are responsible for Comstock 1989; Anthonisen et al. 1986;
lung parenchymal diseases such as silicosis Foxman et al. 1986]. Although pulmonary
[Morgan 1978]. In addition to physical size, function tests can define and measure respira-
the shape and density of inorganic dust parti- tory impairment, they are not a diagnostic tool
cles also influence where they are deposited in for silicosis or a measure of silica exposure
the airways and whether they can be cleared [Wagner 1997], because no single pattern of
from the airways [Becklake 1985]. pulmonary function abnormality is associated
with silica exposure or silicosis [Wagner 1997;
Weill et al. 1994; ATS 1997].
3.5.4 Abnormalities in Pulmonary
Function Tests
3.5.4.2 Epidemiologic Studies
3.5.4.1 Definition Quantitative Estimates of
Pulmonary function tests measure lung vol- Dust-Related Loss of Lung
umes (e.g., vital capacity [VC]), air flow (e.g., Function
expiratory volume in 1 second [FEV1]), blood
Most epidemiologic studies of pulmonary
gas exchange, and other aspects of lung func-
function and occupational exposure to respira-
tion [Rosenstock 1994]. Spirometric pulmo-
ble crystalline silica are cross-sectional studies
nary function tests routinely performed are
that do not provide quantitative modeling of
forced vital capacity (FVC), FEV1, and VC
cumulative dust exposure. They report occupa-
[Parkes 1982]. Lung function tests alone can-
tionally related annual declines in ventilatory
not diagnose any particular disease [Parkes
function in workers with and without silicosis
1982]; however, they are an important part of
(i.e., gold and other hard-rock miners, iron ore
miners, coal miners, talc miners, slate workers,
Respirable particles have aerodynamic diameters less and kaolin workers). Details of these studies
than approximately 10m. are reported elsewhere [ATS 1997; Becklake

1985, 1992; Eisen et al. 1995; NIOSH 1995a; The significance of predicted losses can be
EPA 1996; Graham et al. 1994]. compared with the annual estimated FEV1 de-
cline for a nonminer who smokes one pack of
Thirteen studies with quantitative dust expo- cigarettes per day (10 ml/year) [Xu et al. 1992]
sure data for four silica-exposed cohorts found or with the approximate annual FEV1 decrease
statistically significant associations between in men over age 25 (25 to 30 ml/year) [Bur-
loss of lung function (i.e., FEV1, FVC) and rows 1986].
cumulative respirable dust exposure in coal
miners and South African gold miners A cross-sectional study of 389 male residents
[Oxman et al. 1993]. The study of gold miners of a U.S. hardrock mining community also
[Hnizdo 1992] estimated that a 50-year-old, predicted FEV1 loss [Kreiss et al. 1989b]. Mul-
white South African gold miner (nonsmoker) tiple regression analyses found a significant
who was exposed to gold mine dust (contain- difference (P#0.05) in the mean FEV1 for non-
ing 0.09 mg/m3 of crystalline silica) at an aver- smokers with dust exposure (96% of predicted
age respirable concentration of 0.3 mg/m3 for FEV1) compared with that of nonsmokers
24 years would lose 236 ml of FEV1 (95% CI= without occupational dust exposure (101% of
134337). This loss is equivalent to about predicted FEV1) [Kreiss et al. 1989b].
half of the estimated loss of FEV1 in a typical
U. S. male (nonminer) who smoked one pack 3.5.5 Emphysema
of cigarettes per day for 30 years (i.e., 552 ml
[95% CI=461644]) [Dockery et al. 1988; 3.5.5.1 Definition
Hnizdo 1992]. The combined effects of respi- Emphysema is the abnormal enlargement of
rable dust exposure and smoking on the loss of the air spaces distal to the terminal bronchiole
FEV1 were additive [Hnizdo 1992]. with destructive changes in the alveolar walls
[ATS 1987]. Obvious fibrosis is not present
Epidemiologic studies of Vermont granite [ATS 1987, 1995; Barnhart 1994; Becklake
workers provided quantitative predictions of 1992], although small emphysematous spaces
FEV1 loss based on cumulative past exposure are frequently seen radiographically around
to granite dust. As shown in Table 17, the pre- the edges of large silicotic masses [Weill et al.
dicted FEV1 loss for Vermont granite workers 1994]. The diagnosis of emphysema is defined
is 3 to 4 ml per mg/m3 A year for cumulative by pathologic criteria, and more recently by the
exposure to granite dust and 2.9 ml per presence of avascular spaces on computed
mg/m3 A year for cumulative exposure to tomographic (CT) scans of the lung [Barnhart
quartz dust. This estimate represents a loss of 1994; Hayhurst et al. 1984]. Clinical signs in-
about 6.5 ml of FEV1 for a working lifetime clude hyperinflation on chest radiographs, in-
(i.e., 45 years) of exposure to crystalline silica creased total lung capacity, reduced FEV1, re-
at the current NIOSH REL of 0.05 mg/m3. duced diffusing capacity for carbon monoxide
However, the findings of Theriault et al. (DLCO) [Barnhart 1994], and weight loss
[1974b] were based on measurements that may [Stulbarg and Zimmerman 1996]. Emphysema
have been inaccurate. In 1979, Graham et al. is caused mainly by destruction of the lung pa-
[1981] administered pulmonary function test- renchyma from excess proteolytic enzymes.
ing to about 73% (n=712) of the workers tested One cause of excess proteolytic enzymes and
in 1974 and found small annual increases in the premature development of emphysema is
FEV1. These researchers concluded that tech- the rare homozygous deficiency of the protein
nical deficiencies in the previous studies led to "1-antitrypsin [Laurell and Eriksson 1963;
exaggerated and erroneous estimates of loss. Stulbarg and Zimmerman 1996]. Excess

Table 17. Loss of lung function (FEV 1 )* associated with cumulative exposure to respirable granite dust
Loss of FEV 1
Observed Predicted Adjusted

Reference and Study design, (estimated (ml per for
country cohort, and followup Subgroup ml/yr) mg/m 3@year) smoking Com ments
Eisen et al. Longitudinal study of Nonsmo kers 3472 Yes Significant dose-response
[1995], 618 white male Smokers 5369 (P<0.05) was observed in the

United States granite workers hired Nonsilicotic nonsmokers 4 dropout group but not in the
after 1940, aged survivor group or the total
2565; employed cohort [Eisen et al. 1983]. After
14.7 yr (mean), and 1940, granite dust concentra-
followed 19701974 tions in Vermont granite sheds
for annual pulmonary were <10 million particles per
function testing cubic foot (mppcf), or a respir-
[Eisen et al. 1983]. able silica concentration of
Quartz content of abo ut 0.07 5 mg/m 3 [Davis et al.
dust was 11% [Ho sey 1983].
et al. 1957].
Predicted loss ba sed o n results
of linear regression models.
Theriault Cross-sectional study Granite dust exposure 1.6 , 3 Yes Predicted loss ba sed o n results
et al. [1974b ], of 792 male, current Quartz dust exposure 1.5 ** 2.9 of multiple regression analysis.
United States granite shed workers Exp osure -respo nse relationship
aged 25 65. Q uartz found between cum ulative dust
content of dust was exposure and cumula tive quartz
9% [T heriault 1974a ]. exposure and loss of FEV 1..
*
Forced expiratory volume in 1 second.

In dropout group (i.e., subjects lost to followup). No predicted loss in survivor group.

Per dust-year (i.e., granite shed dust exposure of 0.52 mg/m3 for 40 hr/week for 1 yr).

Included silicotics.
**
Per quartz-year (i.e., quartz dust exposure of 0.05 mg/m3 for 40 hr/week for 1 yr).
61
proteolytic enzymes can also occur when there Of the five studies presented in Table 18, one
is excessive recruitment of polymorphonuclear found that a significant relationship (P<0.05)
leukocytes (e.g., from damage caused by ciga- independent of smoking and silicosis existed
rette smoke) [Stulbarg and Zimmerman 1996]. between gold mine dust exposure** and em-
physema [ et al. 1987]. Two studies found no
relationship between emphysema and years of
Emphysema is classified microscopically by mining [Chatgidakis 1963; Cowie et al. 1993].
type based on the distribution of enlarged air- A study of emphysema type in 1,553 miners
spaces and destruction. The main types of em- with autopsy examinations found that centria-
physema include centriacinar, focal, centrilo- cinar emphysema was more common in smok-
bular, panacinar, distal acinar, and irregular ers, whereas panacinar emphysema was more
(scar) [Barnhart 1994; Parkes 1994]. Focal and common in nonsmokers; exposure to gold
centrilobular emphysema are the types fre- mine dust was related to both types. A miner
quently associated with environmental and oc- who had worked 20 years in high-dust occupa-
cupational exposures. Focal emphysema is as- tions was 3.5 times more likely (95% CI=
sociated with exposure to coal dust, and 1.76.6) to have emphysema (i.e., an emphy-
centrilobular emphysema is commonly found sema score $30%) at autopsy than a miner who
in the upper lobes of the lungs of cigarette did not have a dusty occupation. However, the
smokers and others exposed to chronic irritants authors stated that this result was likely to be
[Barnhart 1994]. However, findings from a true of smoking miners only because there
study of postmortem lung examinations were only four nonsmokers with an emphy-
showed that panacinar or centriacinar were the sema score between 30% and 40% [Hnizdo et
predominant types of emphysema found in the al. 1991]. Later, a study of 242 miners who
lungs of white South African gold miners were lifelong nonsmokers found that the sever-
[Hnizdo et al. 1991]. ity of emphysema at autopsy was not related to
most recent lung function measurements or to
years of gold mining, cumulative dust expo-
3.5.5.2 Epidemiologic Studies sure, or parenchymal silicosis after adjustment
for age at death [Hnizdo et al. 1994]. All of
Studies of emphysema in silica-exposed work- the studies but two [Becklake et al. 1987;
ers (excluding coal miners) show conflicting Hnizdo et al. 1994] found that the presence of
results: it is not clear whether silica exposure is emphysema was significantly associated with
associated with emphysema in all exposed silicosis.
workers or mainly in silica-exposed workers
who smoke. In these studies, researchers have
investigated cohorts of South African gold 3.5.6 Nonmalignant Respiratory
miners, usually by combining historical data Disease (NMRD) Mortality
about occupational exposures and smoking Epidemiologic studies of silica-exposed work-
with postmortem examination of the lungs. ers [Checkoway et al. 1993, 1997; Chen et al.
(Attending physicians in South Africa who 1992; Cherry et al. 1998; Brown et al. 1986;
know or suspect that their deceased patient was Costello and Graham 1988; Costello et al. 1995;
a miner are legally required to remove the
cardiorespiratory organs and send them to the
Medical Bureau for Occupational Diseases if
permission is granted by the next-of-kin **
The number of shifts worked in mining occupations
[Goldstein and Webster 1976]). with high dust exposure.

Table 18. Epidemiologic studies of emphysema in workers exposed to silica dust
Number of
Study design, emphysema Adjusted
Reference and cohort, and deaths or cases Risk for
country followup Subgroup in subgroup measure 95% CI* smoking Com ments
Becklake et al. Unmatched case- Miners who smoked The presence of emphy-
[1987], South control study of 44 20 cigarettes/day before sema at autopsy was not
Africa autopsied white 1960 30.3 7.0141.0 Yes associated with the

gold miners with presence of silicosis.
emphysema > grade
2.0 (i.e., moderate Miners aged 70 at death 26.8 2.0327.0 No Deaths during 19801981
or marked emphy- may not be typical of
sema) and 42 con- deaths in the total cohort
trols without em- Miners who worked 20 yr of South African gold
physema. Miners in occupations with high miners.
and controls were dust exposure 12.7 3.052.0 No
aged 5170 at death
(19801981).
Chatgidakis Prevalence study of Miners with silicosis and Degree of emphysema was
[1963], South 800 consecutive emphysema 297 44.58 ** No not related to years of
Africa autopsies of white service. Pulmonary diffuse
gold miners con- emphysema increased sig-
ducted between nificantly with incidence
January 1957 and and degree of silicosis and
October 1962. with age.
63
64
Table 18 (Continued). Epidemiologic studies of emphysema in workers exposed to silica dust
Number of
Cowie et al. Random sample of Miners by emphysema Yes Presence and grade of
[1993], South 70 black under- grade: emphysema were associ-
Africa ground gold miners Grade 0 (no evidence) 22 ated with silicosis
selected for com- Grade 1 (<25% of lung (P<0.002; P=0.006 ) and
puted tomography affected) 38 smoking (P<0.02; P=0.01)
lung examination Grade 2 (25%50% of but were not associated
from 1,197 partici- lung affected) 10 with years of underground
pants in a cross- mining.
sectional study
conducted in Low agreement (i.e.,
19841985. 37/70) between computed
tomographic and radio-
logic assessments of
silicotic nodule profusion
categories.

Number of
Hnizdo et al. Retrospective co- Miners who worked 20 yr Yes (in some Logistic regression model
[1991], South hort study of the in occupations with analyses) showed significant associ-
Africa relationship of high dust exposure up ation between

emphysema with to age 45 3.5 1.76.6 centriacinar emphysema
lung function and silicosis (P<0.001),
changes in 1,553 emphysema and years of
white gold miners employment in a high-
aged $ 40 with dust occupation for
autopsy examin- miners who smoked,
ation between 1974 age and emphysema, and
and 1987 and pana- average number of
cinar, centriacinar, cigarettes smoked/day
or a mixed type of and emphysema.
emphysema. Possible misclassification
of emphysema type.
65
66
Number of
Hnizdo et al. Retrospective co- Nonsmoking miners with Yes For nonsmokers, degree of
[1994], South hort study of rela- moderate emphysema 4 (all study emphysema at autopsy was
Africa tionship of emphy- subjects were not associated (i.e., P>0.05
sema with lung nonsmokers) in multiple regression
function in 242 model) with years of gold
white gold miners mining, cumulative dust
who were life-long exposure, parenchymal
nonsmokers, were silicosis, or lung function
aged $ 45 at death, impairment after adjusting
and had an autopsy for age at death.
examination during
19741990.
*
Abbreviations: CI=confidence interval; OR=odds ratio.

Dash indicates not reported.

OR for emphysema $ grade 2 at autopsy.

Chi-square value (comparing silicotic miners with emphysema to silicotic miners without emphysema).
**
P<0.00001.

Costello 1983; Steenland and Brown 1995b; 3.6 Autoimmune and Chronic
Steenland and Beaumont 1986; Thomas and Renal Diseases
Stewart 1987; Thomas 1990] and silicotics
[Goldsmith et al. 1995; Brown et al. 1997;
In this century, many published case reports
Rosenman et al. 1995] found significant in-
have described various autoimmune disorders
creases in mortality from NMRD, a broad cate-
gory that can include silicosis and other in workers or patients who were occupation-
pneumoconioses, chronic bronchitis, emphy- ally exposed to crystalline silica [Bramwell
sema, asthma, and other related respiratory 1914; Erasmus 1957; Jones et al. 1976;
conditions. Mehlhorn 1984; Mehlhorn et al. 1990a; de
Bandt et al. 1991; Yanez Diaz et al. 1992;
Pelmear et al. 1992; Caux et al. 1991; Cointrel
The studies of U.S. gold miners [Steenland and et al. 1997; Yamamoto et al. 1994; Guseva
Brown 1995b], U.S. diatomaceous earth work- 1991; Ebihara 1982; Agarwal et al. 1987;
ers [Checkoway et al. 1993, 1997], silicotic Koeger et al. 1991, 1992, 1995; Anandan et al.
men in Sweden and Denmark [Brown et al. 1995; Sanchez-Roman et al. 1993; Aoki et al.
1997] and parts of the United States [Rosen- 1988; Fukata et al. 1983, 1987; Muramatsu et
man et al. 1995], and U.S. pottery workers al. 1989; Masuda 1981; Tokumaru et al. 1990;
[Thomas and Stewart 1987] reported mortality Perez Perez et al. 1986; Bernardini and
ratios (SMRs or PMRs) for some categories of Iannaccone 1982; Siebels et al. 1995; Suratt et
NMRD. However, the other studies either did al. 1977; Meyniel et al. 1981; Hatron et al.
not report SMRs for categories of NMRD or 1982; Masson et al. 1997; zoran et al. 1997;
did not separate silicosis deaths from other cat- Haustein 1998; Cledes et al. 1982; Mehlhorn
egories of NMRD, thus limiting any conclu- and Gerlach 1990]. The most frequently re-
sion about the association of silica exposure ported autoimmune diseases were sclero-
with death from a specific COPD based on derma, systemic lupus erythematosus (lupus),
death certificate data. rheumatoid arthritis, autoimmune hemolytic
anemia [Muramatsu et al. 1989], and derma-
Some studies have reported exposure-response tomyositis or dermatopolymyositis [Robbins
trends for NMRD and silica exposure. The 1974; Koeger et al. 1991]. Case reports have
study of diatomaceous earth workers found a also described health effects such as the fol-
statistically significant exposure-response lowing that may be related to the immunologic
trend for cumulative exposure to respirable abnormalities in patients with silicosis: chronic
crystalline silica and NMRD mortality after renal disease [Saita and Zavaglia 1951; Bolton
adjustment for the effects of age, calendar et al. 1981; Giles et al. 1978; Pouthier et al.
year, duration of followup, and ethnicity (rate 1991; Neyer et al. 1994; Dracon et al. 1990;
ratio=5.35 in the highest exposure stratum Sherson and Jorgensen 1989; Rispal et al.
[$5.0 mg/m3 @ year]; 95% CI=2.2312.80; 1991; Osorio et al. 1987; Bonnin et al. 1987;
15-year exposure lag) [Checkoway et al. Arnalich et al. 1989; Wilke et al. 1996; Banks
1997]. Other studies found exposure-response et al. 1983; Hauglustaine et al. 1980; Slavin et
trends for NMRD mortality and duration of al. 1985], ataxic sensory neuropathy [Toku-
employment [Costello et al. 1995; Thomas maru et al. 1990], chronic thyroiditis [Masuda
and Stewart 1987], years since first exposure 1981], hyperthyroidism (Gravesdisease) [Koeger
[Thomas and Stewart 1987], or qualitative cat- et al. 1996], monoclonal gammopathy [Fukata
egories of silica exposure (none, low, and high) et al. 1983, 1987; Aoki et al. 1988], and poly-
[Thomas and Stewart 1987]. arteritis nodosa [Arnalich et al. 1989].

In addition to these case reports, 13 post-1985 polymyositis, and fibrositis [Ziegler and
epidemiologic studies reported statistically Haustein 1992; Haustein et al. 1990; Otsuki et
significant numbers of excess cases or deaths al. 1998]. A possible mechanism for develop-
from known autoimmune diseases or immuno- ment of scleroderma is a direct local effect of
logic disorders (scleroderma, systemic lupus nonrespirable quartz particles that have pene-
erythematosus, rheumatoid arthritis, and trated the skin of workers [Green and
sarcoidosis), chronic renal disease, and Vallyathan 1996], as observed in skin samples
subclinical renal changes (Table 19). Epi- from deceased scleroderma patients [Mehl-
demiologic studies found statistically signifi- horn et al. 1990b].
cant associations between occupational expo-
sure to crystalline silica dust and several renal In addition to the studies summarized in Ta-
diseases or effects, including end-stage renal ble 19, there may be other epidemiologic data
disease morbidity [Steenland et al. 1990], mor- sets that have not been analyzed by methods
bidity from end-stage renal disease caused by that would detect a possible association be-
glomerulonephritis [Calvert et al. 1997], tween occupational exposure to crystalline sil-
chronic renal disease mortality [Steenland and ica and autoimmune diseases [Steenland and
Brown 1995b], Wegeners granulomatosis Goldsmith 1995]. Further clinical and immu-
(systemic vasculitis often accompanied by nologic studies are needed to characterize the
glomerulonephritis) [Nuyts et al. 1995], and relationship between occupational exposure to
subclinical renal changes [Hotz et al. 1995; crystalline silica and autoimmune diseases.
Boujemaa et al. 1994; Ng et al. 1992a, 1993].
3.7 Other Health Effects
The pathogenesis of glomerulonephritis and
other renal effects in silica-exposed workers is Extrapulmonary deposits of silica have been
not clear. Some case reports provide evidence reported. A review of the literature [Slavin et
of an immunologic injury by immune complex al. 1985] indicates that silica particles may be
formation, and other reports point to a direct transported from the lungs and tracheobron-
toxic effect of silica [Calvert et al. 1997; chial lymph nodes to the spleen, liver, kidneys
Calvert and Steenland 1997; Kallenberg 1995; [Osorio et al. 1987], bone marrow, and extra-
Wilke et al. 1996; Wilke 1997]. The immuno- thoracic lymph nodes as a result of (1) forma-
logic aspects of renal disease are reviewed in tion of silicotic lesions in pulmonary veins,
Ambrus and Sridhar [1997]. (2) erosion of silicotic hilar nodules into pul-
monary veins, and (3) rupture of silicotic nod-
The cellular mechanism that leads from silica ules into the lymphatic system. Roperto et al.
exposure to autoimmune diseases is not known [1995] reported two cases of extrapulmonary
[Otsuki et al. 1998]. One theory is that when silicosis in two water buffaloes that lived on a
respirable silica particles are encapsulated by farm near a quartz quarry. Silicotic lesions
macrophages, fibrogenic proteins and growth were observed in the mesenteric lymph nodes,
factors are generated, and ultimately the im- tonsils, and spleen. In humans with occupa-
mune system is activated [Haustein and tional exposure to silica, peritoneal silicosis
Anderegg 1998; Ziegler and Haustein 1992; has been misdiagnosed as pancreatic carci-
Haustein et al. 1992]. Immune activation by re- noma [Tschopp et al. 1992] or abdominal ma-
spirable crystalline silica may be linked to lignancy [Miranda et al. 1996].
scleroderma, rheumatoid arthritis, polyarthritis,
mixed connective tissue disease, systemic Intravenous injections of silica into the tail
lupus erythematosus, Sjgrens syndrome, veins of rats have resulted in large liver

Table 19. Epidemiologic studies of immunologic, autoimmune, and chronic renal disease
(including subclinical renal changes) in silica-exposed workers
Num ber of
Reference Study design, coho rt, deaths or cases Risk
and country and followup Subgroup in subgroup measure * 95% CI Comments
Boujemaa Cross-sectional case-control Silicotics 116 Miners were examined an average

et al. [1994], study of 116 silicotic, male of 23 yr after cessation of
Belgium underground miners with no exposure. Mean duration of
history of diabetes, exposure was 14.9 yr.

nephrolithiasis, or
hypertension and 61 age- Duration o f expo sure an d severity
matched controls from the of silicosis were not associated
general population. with the measures of renal
dysfunction.
Urine samples were tested
for albumin, retinol-binding Silicotic miners had significantly
protein, and NAG . Serum higher urinary concentrations of
samples were tested albumin (P=0.017), retinol-binding
for creatinine and protein (P=0.0045), and NAG
$ 2-microglobulin. (P=0.0001 ).
Results were similar to those found

by Hotz et al. [1995].
69
Table 19 (Continued). Epidemiologic studies of immunologic, autoimmune, and chronic renal disease
70
Num ber of
Reference and Study design, coho rt, deaths or cases Risk
country and followup Subgroup in subgroup measure * 95% CI Comments
Bo venzi et al. Case-control study of 527 Patients discharged

[1995], Italy patients adm itted to all with diagnosis of
hospitals in Trento province systemic sclerosis
19761991 and discharged (acco rding to specific
with diagnosis of diagnostic criteria):
musculoskeletal disorder or W omen 16 0
connective tissue disease. Men 5 5.20 0.48 74 .1
Each scleroderma case was
matched by age and gender
to two controls who were
without the disease under
study and were from the
same database.

Num ber of
Reference and Study design, cohort, and deaths or cases Risk
country followup Subgroup in subgroup measure * 95% CI Comments
Burns et al. Population-based case- W ome n with self- Adjusted for age, race, and date of
[1996], United control study of 274 women repo rted exposure to birth. Systemic sclerosis was not
States with confirmed systemic the following: associated with self-reported
sclerosis diagnosed in Abrasive grinding or exposures to silica dust or silicone
(including breast implants).

Michigan between 198 5 and sandblasting 3 0.34 0.101.10
199 1 and 1,18 4 female
controls matched by race, Sculp ting or p ottery Sam e study d esign was applied to
age, and geographic region. making 20 1.53 0.892.65 Ohio women with systemic
sclerosis, and results were
W orking in a de ntal published later in a letter [Lacey et
laboratory 3 1.52 0.445.26 al. 1997].
W orking with or
near silica dust,
sand, or other silica
products 12 1.50 0.762.93
Calvert et al. Cohort morbidity study of Miners with cases of First epidem iologic study to
[1997], United 2,41 2 white, male treated end-stage renal examine incidence of end-stage
States underground gold miners disease 11 1.37** 0.682.46 renal disease in an occupational
employed $1 yr between No nsystemic 6 4.22** 1.549.19 cohort.
1940 and 1965 and alive on System ic 4 0.80** 0.222.06
January 1, 1977. Unknown 1 1.54** 0.048.57 Subcohort of gold miners studied
by Steenland and Brown [19 95b].
Mean respirab le silica dust

exposure of this subcohort was
0.05 mg/m 3.
71
72
Num ber of
Cowie [1987 ], Cohort study of incidence of Miners with

South Africa scleroderm a in black gold scleroderma that met
miners seen by the medical diagnostic criteria 10 81.8
service from July 1981 to
June 1986.
Ho tz et al. Cross-sectional case-control 86 Same cohort studied by Bernard et

[1995], Be lgium study of prevalence of al. [1994].
subclinical renal effects in
86 quarry workers Quarry wo rkers had significantly
employed 11 to 20 months higher urinary concentrations of
with no clinical, spirometric, albumin (P<0.000 4), transferrin
or radiographic signs of (P<0.03), retinol-binding protein
silicosis. Controls were (P<0.001), NAG (P<0.001), and
manual workers [Bernard et silicon (P<0.0001 ).
al. 1994] matched by
smoking status, body mass Controls m ay have been expo sed to
index, and age. silica dustoccupational history of
controls was not reported. Narrow
Urine samples were tested range of employment duration may
for albumin, transferrin, have limited the assessment of
creatinine, $ 2- effects.
micro globulin, retinol-
binding protein, silicon, and
NAG . Serum samples were
tested for creatinine and $ 2-
microglobulin.

Num ber of
Klo ckars et al. Cohort morbidity study of Gra nite workers: Mea n quartz concentrations
[1987], Finland 1,026 granite workers hired Awarded disability measured in the granite quarries,
between 1940 and 1971 with pensions for rheu- processing yards, and crushing
followup until the end of matoid arthritis 17 5.08 *** 3.317.79 plants in 19701972 ranged from
0.02 to 4.9 mg/m 3.

1981 for (1) incidence of
disab ility pension awards for Receiving p ensions
rheumatoid arthritis during for rheumatoid
19691981 , (2) prevalence arthritis at end of
of rheumatoid arthritis on study period 10 1.6 recipients expected (P<0.001).
December 31, 1981, and (3)
prevalence of sub jects Receiving free
receiving free medication medication for
for rheumatoid arthritis at rheumato id arthritis
the end of 1981. Referent at end of study
group was composed of period 19 7.5 recipients expected (P<0.001).
Finnish males.
73
74
Num ber of
Ng et al. [1993], Cross-sectional study of W orkers with low-dust- W orkers in the high-exposure
Singapore subclinical renal effects in exposure jobs and no group with $10 yr of employment
67 granite quarry workers radiographic evidence had significantly greater (P<0.05)
with no history of of silicosis 31 urinary concentrations of AMG,
glomerulonephritis, urinary BM G, an d N AG com pared with
calculi, renal disease, W orkers with high- workers in the low-exposure group.
diabetes, hypertension, or dust-exposure jobs and Quantitative dust exposure data not
regular ingestion of <10 yr of emplo yment 17 available.
analgesics. W orkers urine
samples were tested for W orkers with high- Preliminary findings were reported
indicators of glomerular and dust-exposure jobs and in Ng et al. [1992a].
tubular functions (i.e., $10 yr of employment 19
albumin, AMG , BM G, and Further studies are needed to define
NAG ). the clinical significance of AMG,
BM G, and NAG as indicators of
renal dysfunction in silica-exposed
workers.

Num ber of
Reference and Study design, cohort and deaths or cases Risk
country followup Subgroup in subgroup measure * 95% CI Comments
Nuyts et al. Case-control study of Patients with Wegeners Study had small sample size and
[1995], Be lgium occupational exposures of granulomatosis (renal was no t designed sp ecifically to
16 p atients diagnosed with involvement) and examine exposure -response
W egeners granulomatosis reported occupational relationship of Wegeners

at six Belgian re nal units exposure to silica 5 5.0 1.4 11.6 granulomatosis with occupational
between June 1991 and June exposure to silica. Fu rther stud y is
1993. Each patient was needed.
matched (by age, sex, and
region of resid ence) with
two co ntrols randomly
selected from lists of voters.
Rafnsson et al. Population-based case- Sarcoido sis patients No matching of ca ses with
[1998], Iceland control study of residents in with occupational controls.
a district with a diatoma- exposure to diatoma-
ceous earth processing ceous earth and Mean values of personal samples of
plant. Population included 8 cristobalite at the respirable c ristoba lite dust taken in
sarcoidosis patients who community plant 6 13.2 2.0 140 .9 1978 and 1981 ranged from 0.002 to
were linked to a file of all 0.6 mg/m 3.
past and present workers
employed at the plant after Stratification by number of hr
it opened in 1967. 70 worked ($1,000 hr or <1 ,000 hr)
controls were random ly indicated a d ose-response trend.
selected from the district Furthe r study of sarcoidosis and
population. silica exposure is needed.
75
76
Num ber of
Rosenman and Cohort morbidity study of Patients with silicosis No pa tients had silicosis and
Zhu [1995] men and women aged $20 and rheum atoid scleroderma.
and discharged from arthritis:
Michigan hosp itals Wom en 0
19901991. Men 3 3.2 ** 1.1 9.4
Sluis-Cremer Case-control study of 79 1.18 0.265.38 Contro lled for cumulative dust
et al. [1985], silicosis in 79 white gold exposure .
South Africa miners diagnosed with
definite or probable Although reported ORs suggested
progressive systemic no association be tween silicosis
sclerosis between 1955 and and pro gressive systemic sclerosis,
June 198 4. Ra ndomly cases had higher cumulative dust
selected control group of 79 exposure (P<0.001).
miners in same patient index
examined between May This study was not designed to
1970 and April 1971; examine the possibility of a direct
matched by age; without association be tween silica dust
progressive systemic exposure and p rogre ssive system ic
sclerosis. sclerosis.
Sluis-Cremer Case-control study of Miners with definite Although the reported ORs
et al. [1986], silicosis in 157 w hite gold rheumato id arthritis 91 3.79 1.728.36 suggested that gold m iners with
South Africa miners diagnosed with probab le or definite rheumatoid
definite or probable Miners with probable arthritis were more likely to have
rheumatoid arthritis between rheum atoid arthritis 66 1.94 0.814.63 silicosis as well, the study was not
1967 and 1 979. Each case designed to examine the possibility
was matched by age to a of a direct association between
control subject without silica exp osure and rheum atoid
rheumato id arthritis. arthritis. The results could not be
explained by cumulative dust
exposure or the intensity of
exposure to gold mine d ust.

Num ber of
Steenland et al. Population-based case- Men with end-stage Possible overreporting of exposure
[1990], United control study of occupa- renal disease who re- by cases.
States tional exposures of ported occupational
325 men listed in the exposure to silica 87 1.67 1.022.74

Michigan kidney registry
and diagnosed with end-
stage renal disease
(excluding diabetic,
congenital, and obstructive
nephropathies) between
197 6 and 198 4. 32 5 controls
matched by age, race, and
area of residence.
Steenland et al. Pro portionate mortality Granite cutters: Study included all underlying and
[1992], United study of 991 granite cutters Arthritis deaths 17 2.01 1.173.21 contributing c auses o f mortality
States who died after 1960 after 1960 and other significant
compared with causes of Chro nic renal conditions that were documented on
death in U.S. population. disease deaths the death certificate.
(ICD 9 categ ories
582 , 583 , 585 ,
587) **** 26 2.18 1.433.20
77
78
Num ber of
Steenland and Mortality study of 3,328 Arthritis (ICD9 Study included all underlying and
Brown [19 95b], white male gold miners categories 711716, contributing c auses o f mortality
United States employed underground 720721) (see after 1960 and other significant
$1 yr between 1940 and comm ents) 17 2.19 1.273.50 conditions documented on the
1965 and followed for death certificate.
mortality from 1 977 to Other musculoskeletal
1990. Mortality rates of disease as well as Statistically significant exposure-
U.S. males used for sclerosis, scleroderma, response trend (P<0.05) for chronic
comparison. and lupus (ICD9 renal disease mortality and
categories 710, cumulative dust exposure.
717719, 722729,
731739) (see
comm ents) 10 2.14 1.033.94
No nmalignant skin
diseases (ICD9
categories 690709)
(see com ments) 10 2.45 1.174.51
Chro nic renal disease in

miners in highest
cumulative dust expo-
sure ca tegory (i.e.,
$48,00 0 dust-days) 8 2.77 1.205.47
*
Odds ratio unless otherwise indicated.

Abbreviations: Dash indicates not reported; AMG=alpha-1-microglobulin; BMG=beta-2-microglobulin; CI=confidence interval; NAG=beta-n-acetyl-D-glucosaminidase; OR=odds ratio.

None exposed.

For history of silica dust exposure.
**
Standardized incidence ratio (SIR).

That is, caused by glomerulonephritis or interstitial nephritis.

Incidence (cases) per million black gold miners. Incidence in general population of black men of similar age (3357) was 3.4 cases per million (P<0.001).

Disability cases.
***
Rate ratio.

Receiving arthritis medication through national insurance plan.

OR is for presence of silicosis.


PMR.
****
ICD9 is the International Classification of Diseases, 9th Revision [WHO 1977].

SMR.

Reported in Steenland and Goldsmith [1995].
granulomas and hepatic silicosis [Kanta et al. preceded by pulmonary arterial hypertension.
1986]. In workers exposed to crystalline silica, An epidemiologic case-control study of 732
hepatic changes [Liu et al. 1991], hepatic or white South African autopsied gold miners re-
hepatosplenic silicosis [Clementsen et al. ported a statistically significant association
1986; Oswald et al. 1995], and hepatocellular (P<0.05) of cor pulmonale with extensive
carcinoma [Clementsen et al. 1986] have been and slight silicosis [Murray et al. 1993].
identified. Two studies reported a significantly
higher proportion (P<0.05) of symptomatic Pulmonary alveolar proteinosis is a rare respi-
hepatic porphyria (a chronic metabolic dis- ratory disease identified by an accumulation
ease) in silica-exposed workers compared with of phospholipid material in the alveoli
control groups having no history of occupa- [McCunney and Godefroi 1989]. Cases of this
tional silica exposure [Okrouhllik and Hyke disease were identified in a U.S. cement truck
1983; Zoubek and Kordac 1986]. However, the driver [McCunney and Godefroi 1989], a U.S.
effect of silica on porphyrin synthesis and me- sandblaster [Abraham and McEuen 1986], and
tabolism is not clear. In one study, alcohol con- a French ceramics worker [Roeslin et al. 1980].
sumption (quantity not specified) may have Each worker had been potentially exposed to
been a confounder [Okrouhllik and Hyke crystalline silica.
1983].
Skin absorption of crystalline and amorphous
Mowry et al. [1991] reported a case of a cuta- silica particles from soil, and subsequent
neous silica granuloma in a 57-year-old stone- obstructive lymphopathies related to the
mason. Silica granulomas are firm, nontender fibrogenic effects of the particles may be re-
dermal or subcutaneous nodules that usually lated to the development of nonfilarial tropical
appear at least several years (mean=10 years) elephantiasis (podoconiosis) in the lower legs
after the exposure to silica. They may appear as of residents of East Africa and certain volcanic
a result of occupational exposure or trauma areas [Frommel et al. 1993; Fyfe and Price
[Kuchemann and Holm 1979; Murphy et al. 1985; Price and Henderson 1981].
1997] and are usually treated by excision. The
mechanism that causes the silica crystals in the Silica dust exposure may be associated with
tissue to form a granuloma is unknown. abrasion-related deterioration of dental health.
Petersen and Henmar [1988] reported a 100%
Cor pulmonale (enlargement of the right ven- prevalence of dental abrasion in a group of
tricle of the heart because of structural or 33 Danish granite workers. The authors recom-
functional abnormalities of the lungs) may oc- mended that dust concentrations be reduced,
cur as a complication of silicosis [Green and that workers wear face guards, and that dental
Vallyathan 1996] and other pneumoconioses abrasion from occupational dust exposure be
[Kusiak et al. 1993a]. This condition is usually considered an occupational disease.

4 Experimental Studies
This section provides an abbreviated review of 3. The studies lack information about control
various experimental research studies. The groups, diagnostic criteria for silicosis, and
reader is encouraged to consult the cited mate- baseline levels of markers.
rials for complete information.
4. Study results are inconsistent.
4.1 Biomarkers
A biomarker can indicate (1) the occurrence of Further research on biomarkers in silica-
exposure, (2) the effects of exposure, (3) the exposed workers is needed to do the following:
presence of early or frank disease, or (4) the
susceptibility to disease or early effects of ex- 1. Quantify the exact amount of soluble prod-
posure [Committee on Biological Markers of ucts in bronchoalveolar lavage in individ-
the National Research Council 1987; Schulte ual patients to provide more information
1995]. Useful biomarkers require (1) a defini- about the mechanisms of fibrogenesis
tive, validated link with the exposure or the [Sweeney and Brain 1996]
risk of disease and (2) evidence of a dose-
response relationship between the marker and
2. Determine whether silicosis or silica-related
the exposure [Schulte 1995]. The relationship
lung cancers are associated with a specific
between respirable silica dust exposure and sil-
gene or gene pattern
icosis is well established. However, the
complex chain of cellular responses that leads
to fibrosis and silicosis has not been fully dis- 3. Determine whether a relationship exists
covered. The usefulness of biomarkers as a between changes in immunoglobulin con-
screening tool for silicosis risk will be realized centrations and silica exposure
when biomarkers in the chain of complex cel-
lular responses are validated for their relation- 4. Determine whether a dose-response rela-
ship to disease. In addition, the studies of tionship exists between changes in certain
blood, serum, sputum, bronchoalveolar cellular components (lymphocytes and
lavage samples, and gene patterns of silica- Clara cell protein) and silica exposure
exposed workers or silicotics (Table 20) are in-
conclusive for the following reasons: Detailed reviews of the immunologic response
to silica and other mineral dusts are available
1. The numbers of subjects are small, and few elsewhere (i.e., Heppleston [1994]; Haslam
studies of similar markers exist for com- [1994]; Weill et al. [1994]; Davis [1991,1996];
parison. Kane [1996]; Driscoll [1996]; Sweeney and
Brain [1996]; Hook and Viviano [1996]; Gu
2. The studies lack control for factors other and Ong [1996]; Iyer and Holian [1996];
than silica exposure that could change im- Weissman et al. [1996]; Mossman and Churg
munoglobulin concentrations. [1998]).

Table 20. Molecular epidemiology studies of biomarkers for carcinogenesis or silicosis
Reference and
country Study design a nd coho rt* Num ber of subjects Biologic marker Results Com ments
Bernard et al. Belgium q uarry workers 86 quarry workers and Serum and sputum Decreased conc entrations Controls may have been
[1994], who had worked <2 yr. 86 contro ls Clara cell pro tein of serum and sputum exposed to silica dust.
Belgium Controls were manual (Clara cell 16) Clara cell protein in Short duration of exposure
workers without silica dust quarry workers (P=0.04) among quarry workers may
exposure, matched by comp ared with controls. have limited the analysis.
smoking status, bo dy mass Authors state that serum

index, and age. Clara cell 16 may be
marker for toxic effects of
silica particles on
respiratory epithelium.
Bo rm et al. Male silicosis patients at a 20 silicosis patients Blood and plasma Silicosis patients had sig- Small number of subjects.
[1986], hospital in the Netherlands; (15 coal miners, 4 ceram- concentrations of nificantly higher concen- Controls were not inter-
Netherlands exposed to silica for 1038 ics workers, 1 foundry hemoglobin, reduced trations o f red blood cell viewed for their occupa-
yr. Controls were healthy worker); 48 contro ls and oxidized gluta- glutathione (P<0.0001 ). tional histo ry, and def-
male, Caucasian blood thione, glutathione inition of healthy was
donors aged 5065. peroxidase, and super- not reported. Medication
oxide d ismutase adm inistered to patients
may have been a con-
founder.
81
Table 20 (Continued). Molecular epidemiology studies of biomarkers for carcinogenesis or silicosis
82
Reference and
Bra ndt-Rauf Prospective study of com- 46 patients: 36 with as- 9 serum oncogene- 7/15 asbestosis pa tients Prospective study found
et al. [1992], pensated pneumoc oniosis bestosis and 10 with ILO related proteins or had ras (p21) oncogene, that 3 o f the 10 silicosis
Finland patients; 91 blood samples category $1/1 silico sis growth factors: but no oncogene-related patients developed cancer
were collected between growth factor PDGF- proteins were found in during the study period
1983 and 1987. Cancer B (sis), TGF-$ 1, ras, the 10 silicosis patients. (1983 198 7). 2 p atients
cases were identified in the fes, myb, int-1, mo s, All silicosis patients had had bladder cancer and
Finnish Cancer R egistry. src, myc PDGF-B (sis) grow th 1 had lung cancer. PDGF
4 silicotics had worked as factor; only 42% of may be a possible marker
stone workers, 1 as a stone asbestosis patients had for development of severe
crusher, 2 as miners, and PDGF-B (sis). or progre ssive silicosis.
3 as foundry workers. 3 sili- Study results suggest
cotics with lung cancer different pathogeneses for
were matched by age and silicosis and asbestosis.
smoking habits with 7 con-
trols without cancer.

Reference and
Calhoun et al. Healthy, male, employed 9 wo rkers and 9 contro ls IgG, IgM, IgA, No significant differences Authors concluded that
[1986], United granite workers (non- albumin, and total in mean serum concen- inhalation of granite dust
States smokers) with no clinical or protein (all were trations between workers might initiate and su stain
radiographic evidence of measured in BAL and contro ls. Statistically an immune-inflammatory
silicosis. V olunteer controls fluid and serum) significant differences response.
of similar age and smoking (i.e., higher concentra-

history with no history of tion) between IgG, IgA,
occupational ex posure to IgM co ncentrations and
dust. All workers and con- lymphocyte c ounts in
trols had BAL. lavage fluid of workers
comp ared with controls.
Glikov Miners, drillers, and tun- 40 workers and 40 con- Serum IgG, IgM ,and No difference in IgM Method of silicosis diag-
[1982], nelers, half with silicosis, trols IgA concentration. nosis not reported.
Slovakia aged 4381, exposed 230 yr. Significantly elevated
Control group of healthy average concentration of
blood donors aged 4282 IgG in workers compared
with no history of exposure with controls (P<0.001).
to inorganic dusts. Significantly elevated
average concentration of
IgA in workers compared
with controls (P<0.05).
No significant differences
in IgG, IgM, or IgA be-
tween silicotic and non-
silicotic workers.
83
84
Reference and
Gualde et al. Caucasian silicosis patients 75 p atients, 160 contro ls 27 HL A antigens Prevalence of B7 antigen Sma ll numb er of co ntrols
[1977], France (radiograp hic diagnosis) in first group, and 46 in (serum) was significantly less may have resulted in low
who had a silica-related control group of porce- (P<0.05 before correction statistical power to detect
occupation for 1040 yr lain workers for multiple comparisons any differences after cor-
(38 gold, wolfram, and uran- of tested antigens) than in rection for multiple com-
ium miners; 35 porcelain healthy or silica-exposed parisons. Authors sug-
workers; 2 quarry workers). controls. N o other signif- gested that presence of B7
No rmal and healthy icant differences found antigen may be related to
Caucasian controls plus between silicotics and resistance to development
second control group of controls. of silicosis. (See also
porcelain workers Sluis-Cremer and Maier
emp loyed 20 40 yr but with [1984] later in table.)
no clinical or radiographic
signs of silicosis.
Ho nda et al. Japanese silicosis patients 46 p atients, 315 contro ls HLA -DQ alleles, Some HLA-DQ alleles Source and occupational
[1993], Japan who had been sandb lasters for HLA typing, and 94, RFLP patterns, and were more frequent in history of control group
and who had radiographic 127 , 100 , or 12 8 controls IGLV gene extracted silicosis patients (P<0.05). not reported. Definition of
evidence of silicosis. for other analyses from peripheral gran- RFLP pattern of healthy not rep orted .
Controls were healthy ulocytes (medium not C4A3 C4B 5 allotype and Potential confounders of
unrelated Ja panese. reported) IGL V m ore frequent in exposure and immuno-
silicosis patients (P<0.05). logical outcomes not re-
ported.
Authors suggested that

their findings indicate that
a gene for silicosis may be
near the H LA-B locus.
Validation of these
findings is needed.

Reference and
Husgafvel- Finnish white males with 5 patients with silico sis Mutation of p53 gene Tw o of the five silicosis Subjects for study were
Pursiainen lung cancer (see comments). and 16 p atients with and serum elevation patients had lung tumors drawn from cohort studied
et al. [1997], asbestosis of p53 protein (serum with DNA mutations of by Brandt-Rauf et al.
Finland samples were not the p53 gene. [1992] (described earlier).
available for the
silicosis patients) The results of the serum

tests do not support use of
p53 assay by itself as a
screening tool for lung
cancer because only 36%
of cancer ca ses tested pos-
itive for the mutant pro-
tein. The autho rs state that
it may be a useful bio-
marker if com bined with
serum assays for altered
oncoproteins as in the
study by Brandt-Rauf
[1992].
Karnik et al. Male slate pencil worke rs. 130 silica-exposed work- Serum IgG, IgM , and Higher concentrations Results may have been
[1990], India Controls with no history of ers: 80 with ILO category IgA (P<0.05) of IgG, IgM, confounded by bacterial
occupational ex posure to 1, 2, or 3 silicosis and 50 and IgA in silicotic infections in some work-
dust or silica. controls workers compa red with ers. Authors stated that an
controls. increase in immuno-
globulin concentrations
was not a marker for
severity of silicosis.
85
86
Reference and
Ko skinen et al. Finnish male silicosis pa- 27 patients; 27 non- Serum HL A antigens Higher prevalence of Authors state HLA-Aw19
[1983], Finland tients (ILO catego ry $1/1) silicotic, silica-exposed HLA-Aw19 in silicotics may b e marker for silicosis
who had b een exposed to controls; and 900 blood compared with non- progression in Finnish
silica dust $10 yr. Non- donor co ntrols silicotic, silica-exposed population, but larger
silicotic controls matched controls (P=0.02). Higher study groups are needed.
by age (5 yr), duration of prevalence of HLA-Aw19
silica exposure ( 5 yr), and in unexposed blood donor
work enviro nment. Addi- group than in silica-
tional control group of exposed controls (P=0.04).
healthy Finnish blood
dono rs.
Kre iss et al. Silicotic residents from 49 silicotics, 1,029 No rth HLA-A, HLA-B, Significantly higher prev- Population-based study
[1989a], hardrock mining town in American controls, and HLA-DR, and HLA- alence of A29 and B 44 in design.
United States Colorado who had mined 1,0611,082 international DQ antigens (blood) silicotics comp ared with
for 558 yr and were aged controls two control groups A29 is a component of
30 59 w hen diagnosed with (P<0.05 after correction Aw1 9 (see Ko skinen et al.
ILO catego ry $1/0 silico sis. for num-ber of antigens [1983] abo ve).
Published antigen preva- tested).
lences of North American
whites and international
whites used for comparison.

Reference and
Pevnitskiy Male Russian patients aged 32 silicosis patients and 11 HL A antigens (6 Prevalence of HLAB8 Occupational history of
et al. [1978], 30 50 w ith Stage I sili- 32 contro ls on A locus and 5 on B and HLAB1 3 in sili- control group not reported.
Russia cosis who had been em- locus) (serum) cotics was twice the prev- Definition of healthy not
ployed >10 yr in occupa- alence in the control reported. Definition of
tions with exposure to group (P value not re- Stage I silicosis not re-
quartz dust (i.e., casting ported). ported. Small number of

shop cleaners, sandblasters, subjects and controls.
and mold ers). Contro ls
were clinically healthy
Russian male blood donors
aged 3050.
Sluis-Cremer W hite So uth African gold 101 miners (45 silicotics 29 HL A antigens Significantly fewer sili- Source of control group
and Maier miners who had been ex- of category $1/0 and (medium not reported) cotics had B40 antigen not rep orted . No signif-
[1984], South posed to at least 20 low- 56 nonsilicotics) and com pared with b oth icant difference was found
Africa dust years. Control group 279 contro ls silica-exposed and non- in the prevalence of B7,
of Cauca sian nonminers. exposed comparison which does not agree with
groups (P=0.02). the findings of Gualde et al.
[1977] (discussed earlier).
Sobti and Male sandstone-crushing 50 workers and 25 Blood: SCE and CA Higher proportion of SCE Dust contained 50%60%
Bhardwaj workers. Control group of controls and CA in silica-exposed crystalline silica, 14%16%
[1991], India local university teachers workers compa red with aluminum oxide, and
and studen ts. controls (2.72% versus 4% 5% iron oxide. P os-
1.28 %; P<0.01). sible effect of socioeco-
More SC Es (P<0.01) in nomic differences between
smokersboth silica- workers and control group
exposed and nonexposed. not accounted for. No
statistical test for correla-
tion between duration of
exposure and levels of
SCE and CA. Silica expo-
sure concentrations not
reported.
87
88
Reference and
W atanabe et al. Males aged 347 8, hospital- 82 patients and 25 Total blood Silicosis patients with Source and occupational
[1987], Japan ized w ith ILO catego ry $2 controls lymphocyte count and low lymphocyte co unts history of control group
silicosis and employed as lymphocyte subsets: (#1,50 0 l) had signifi- not reported. Definition of
tunnel workers or metal OKT3+, OKT4+, cantly increased IgG and normal controls not
miners for a mean duration OKT 8+, OKIa1+ IgA levels co mpa red with reported. Potential con-
of 23 .8 yr. N ormal ma le controls (P<0.001). founders of exposure and
controls aged 4672 with- Serum IgG, IgM, Decreased numb er of cir- immunological outcomes
out silicosis. IgA, IgD, and IgE culating T-cells in pa- not reported.
tients.
Need further study of rela-
tionship of silicosis with
serum immunoglo bulin
levels and lymph ocytes.
*
Studies were cross-sectional unless otherwise indicated.

Abbreviations: BAL = bronchoalveolar lavage; CA = chromosomal aberrations; HLA = human leukocyte antigen; Ig = immunoglobulin; IGLV = immunoglobulin lambda
variable chain; ILO = International Labour Organization; PDGF = platelet-derived growth factor; RFLP = restriction fragment length polymorphism; SCE = sister chromatid
exchange; TGF = transforming growth factor.

4 EXPERIMENTAL STUDIES
4.2 Cytotoxicity transferase) gene mutation [Driscoll et al.

1997], or aneuploid or tetraploid cells
Respirable crystalline silica is known to cause [Price-Jones et al. 1980; Oshimura et al. 1984;
silicosis; however, the molecular mechanism Hesterberg et al. 1986]. An in vivo treatment of
responsible for the cellular injury that precedes rats with quartz induced mutation in rat alveo-
the lung disease is unknown. Extensive in vitro lar epithelial cells (Table 21) [Driscoll 1995;
and in vivo research has been conducted to 1997].
evaluate the effects of crystalline silica on
mammalian cells. Several mechanisms have Pairon et al. [1990] tested tridymite (i.e.,
been proposed to explain the cause of the cellu- Tridymite 118) and quartz (i.e., Min-U-Sil 5)
lar damage [Lapp and Castranova 1993]: particles for genotoxic effects. Tridymite in-
duced a significant number of sister chromatid
1. Direct cytotoxicity of crystalline silica exchanges (SCEs) in co-cultures of human lym-
phocytes and monocytes (P<0.05 compared
2. Stimulation of the alveolar macrophages with control cells) at doses of 5 and 50 g/cm2
by silica and subsequent release of (87.9% of the tridymite particles had a diame-
cytotoxic enzymes or oxidants ter <1 m). However, the number of SCEs in
purified human lymphocytes that were treated
3. Stimulation of the alveolar macrophages to with the same doses of tridymite particles did
release inflammatory factors (e.g., inter- not differ significantly from control cells
leukin-8, leukotriene B4, platelet-activating [Pairon et al. 1990]. Results of the same exper-
factor, tumor necrosis factor, platelet- iments with quartz did not yield a clear conclu-
derived growth factor) that recruit poly- sion about the ability of quartz to induce a sig-
morphonuclear leukocytes, which in turn nificant number of SCEs (Table 21) [Pairon et
may release cytotoxins al. 1990].
4. Stimulation of the alveolar macrophages to
release factors that initiate fibroblast pro- In vitro cellular transformation systems
duction and collagen synthesis (e.g., model the in vivo process of carcinogenesis
interleukin-1, tumor necrosis factor, [Gao et al. 1997; Gu and Ong 1996]. The abil-
platelet-derived growth factor, fibronectin, ity of quartz to induce dose-dependent mor-
and alveolar macrophage-derived growth phological transformation of cells in vitro has
factor) been demonstrated in experiments with Syrian
hamster embryo cells [Hesterberg and Barrett
4.3 Genotoxicity and Related 1984] and mouse embryo BALB/c-3T3 cells
[Saffiotti and Ahmed 1995]. Gu and Ong
Effects
[1996] also reported a significant increase in
Some studies have demonstrated the ability the frequency of transformed foci of mouse
of quartz to induce micronuclei in mammalian embryo BALB/c-3T3 cells after treatment with
cells in culture [Hesterberg et al. 1986; Min-U-Sil-5 quartz. These studies indicate that
Nagalakshmi et al. 1995; Oshimura et al. 1984] crystalline silica can morphologically trans-
(Table 21). However, other in vitro studies form mammalian cells. However, further stud-
did not observe chromosomal aberration ies are needed to determine whether the trans-
[Nagalakshmi et al. 1995; Oshimura et al. 1984], forming activity of silica is related to its
hprt (hypoxanthine-guanine phosphoribosyl carcinogenic potential.

Table 21. Summary of the genotoxic effects of quartz in mammalian cells
In vitro studies In vivo studies
Number of
positive Number of positive
studies/number of studies/number of
Genotoxic effect studies availab le Reference studies availab le Reference
Sister ch romatid 1 */3 Price-Jones et al. [1980] 1 */1 Sobti and Bhardw aj
exchange Pairon et al. [1990] [1991]
(2 expe riments)
Chro mosoma l 0/3 Nagalakshmi et al. [1995] 1 */1 Sobti and Bhardw aj
aberrations (2 expe riments) [1991]
Oshimura et al. [1984]
Micronuclei 3/4 Oshimura et al. [1984] 0/1 Vanchugova et al.

Hesterberg et al. [1986] [1985]
Nagalakshmi et al. [1995]
(2 experiments)
Aneuploidy or 0/3 Price-Jones et al. [1980]; 0/0

tetraploidy Oshimura et al. [1984];
Hesterberg et al. [1986]
hprt mutation 0/1 Driscoll et al. [1997] 2/2 Drisc oll et al.
[1995, 1997]
Source: IARC [1997].
*
One questionably positive study available.
One experiment by Nagalakshmi et al. [1995] showed an increase in the frequency of micronucleated cells at all concentrations
tested, but the increase was statistically significant (P<0.05) only at the two highest concentrations tested.
hprt = hypoxanthine-guanine phosphoribosyl transferase.
Mutagenic response associated with inflammation.

Researchers at the National Cancer Institute macrophages, but DNA-damaging activity

have examined the ability of quartz, cristo- was restored with time as the phospholipid
balite, and tridymite particles to cause deoxyri- surfactant was removed by intracellular diges-
bonucleic acid (DNA) damage (i.e., strand tion [Liu et al. 1998].
breakage) [Saffiotti et al. 1993; Shi et al. 1994;
Daniel et al. 1993; Daniel 1993, 1995]. Al- Shi et al. [1998] recently reviewed published
though the results of those studies demon- literature on (1) the generation of reactive
strated the ability of crystalline silica to cause oxygen species (ROS) directly from silica and
damage to isolated DNA in acellular systems, from silica-stimulated cells, (2) the role of
reviewers at IARC [1997] recently stated that ROS in silica-induced DNA damage and
the relevance of these assays to assess silica-induced cell proliferation, and (3) other
quartz-related genetic effects in vivo was silica-mediated reactions. A proposed mecha-
questionable because (1) the nonphysio- nism for silica-induced generation of ROS spe-
logical experimental conditions did not apply cies and carcinogenesis is described by Shi et
to intracellular silica exposure and (2) very al. [1998]. Experimental research is continuing
high doses of silica were used in the DNA to determine whether crystalline silica parti-
breakage assays [IARC 1997]. cles have a direct genotoxic effect that could
cause lung tumor formation in humans.
Several studies conducted since the IARC re-
view found that crystalline silica induced DNA
damage (i.e., DNA migration). Zhong et al.
4.4 Carcinogenicity
[1997] found that by using the alkaline single Experimental evidence of the carcinogenicity
cell gel/comet (SCG) assay, crystalline silica of quartz particles is based on the results of
(Min-U-Sil 5) induced DNA damage in cul- long-term inhalation and intratracheal instilla-
tured Chinese hamster lung fibroblasts (V79 tion studies of rats, which are summarized in
cells) and human embryonic lung fibroblasts Tables 22 and 23 [Saffiotti et al. 1996]. Sev-
(Hel 299 cells) [Zhong et al. 1997]. Amor- eral issues are apparent from the results of the
phous silica (Spherisorb), but not carbon black, rat studies [Holland 1995]:
was also found to induce DNA damage in
these mammalian cells. However, the DNA-
1. The appearance of tumors (usually adeno-
damaging activity of amorphous silica was not
carcinomas or epidermoid carcinomas) is a
as high as the damaging activity of crystalline
late phenomenon.
silica [Zhong et al. 1997]. Liu et al. [1996,
1998] challenged Chinese hamster lung
fibroblasts with dusts pretreated with a 2. Lung fibrosis is usually present in the rats
phospholipid surfactant to simulate the condi- with tumors.
tion of particles immediately after deposition
on the pulmonary alveolar surface. Results of 3. No adequate dose-response data exist be-
the experiments showed that untreated cause multiple-dose experiments have not
Min-U-Sil 5, Min-U-Sil 10, and noncrystalline been conducted in the rat except for the in-
silica induced micronucleus formation in a halation study by Spiethoff et al. [1992].
dose-dependent manner, but surfactant pre-
treatment suppressed that activity [Liu et al. 4. Comparability of the intratracheal instilla-
1996]. A subsequent experiment found that tion and inhalation studies is difficult be-
surfactant pretreatment suppressed quartz- cause of notable differences in methods
induced DNA damage in lavaged rat pulmonary and materials.

Table 22. Summary of data on lung tumors induced in rats by crystalline silica
Incidence of lung
tumors *
Sample and exposure Rat Treated

conditions strain Sex rats Co ntro ls Reference Com ments
Quartz (Min-U-Sil 5):

Intratracheal Sprague- 6/36 0/58 Holland Treated rats had
instillation of Dawley et al. [1983] 1 adenom a and
7 mg/wk for 10 wk 5 carcino mas.
Inhalation (no se only) Fischer F 20/60 0/54 Holland Treated rats had
of 12 5 m g/m 3 for 344 et al. [1986] 6 aden omas,
up to 2 yr 11 adenoc arcinomas, and
3 epide rmoid carcinomas.
Inhalation of Fischer F 10/53 0/47 Dagle et al. Treated female rats had
51.6 mg/m 3 for various 344 M 1/47 0/42 [1986] 10 epidermoid
durations; sacrificed at carcinom as.
24 months
Treated male rats had
1 epidermoid carcinoma.
Intratracheal instilla- Fischer M 30/67 1/75 Gro th et al. Treated rats had
tion of 2 0 mg in left 344 [1986] 30 ad enocarc inomas.
lung; sacrificed at 12, Controls had
18, or 22 months, or 1 adenocarcinoma.
found dead
Novaculite (i.e., micro-

crystalline quartz):
Intratracheal instilla- Fischer M 21/72 1/75 Gro th et al. Treated rats had
tion of 2 0 mg in left 344 [1986] 20 adenoc arcinomas and
lung; sacrificed at 12, 1 epidermoid carcinoma.
18, or 22 months, or Controls had 1 adeno-
found dead carcinoma.
Raw shale dust:

of 15 2 5 1 mg/m 3 344 1/15 et al. [1986] 2 aden omas,
(average q uartz 8 adenocarcinoma s, and
content: 8%12%) 7 epide rmoid carcinomas.
Controls had 1 adenoma.

Table 22 (Continued). Summary of data on lung tumors induced in rats by crystalline silica
Incidence of lung
tumors *
Sample and exposure Rat Treated

conditions strain Sex rats Co ntro ls Reference Com ments
Spe nt shale d ust:

of 17 6 7 5 mg/m 3 344 1/15 et al. [1986] 2 aden omas,
(average q uartz 8 adenocarcinoma s, and
content: 8%12%) 1 epiderm oid carcino ma.
Controls had 1 adenoma.
Quartz (DQ 12):

Inhalation of 1 mg/m 3 Fischer F 12/50 3/100 Muhle et al. Treated female rats had
for 24 months 344 (male and [1989] 2 keratinizing cystic
female) squamous cell tumors,
Fischer M 6/50 2 adenomas, and
344 8 aden ocarcino mas.
Treated male rats had
2 keratinizing cystic
squamous cell tumors,
2 aden ocarcino mas,
1 adenosquam ous carcin-
oma , and 1 squamou s cell
carcinoma.
Controls had 2 adenomas
and 1 adenocarcinoma.
Inhalation (no se only) W istar F 62/82 0/85 Spiethoff Treated rats had
of 6 m g/m 3 for 29 days et al. [1992] 8 aden omas,
followed by lifetime 17 bronchioloalveolar
observation carcinomas, and
37 sq uamous cell
carcinom as.
Inhalation (no se only) W istar F 69/82 0/85 Spiethoff Treated rats had
of 30 mg/m 3 for et al. [1992] 13 ad enomas,
29 days followed by 26 bronchioloalveolar
lifetime observation carcinomas, and
30 sq uamous cell
carcinom as.
Source: Adapted from Saffiotti et al. [1996].
*
Number of lung tumors per number of rats observed.

Not reported.

Investigators used two control groups.

Table 23. Lung tumors induced in Fischer 344 rats by a single intratracheal instillation of quartz
Incidence of
lung tumors Total
Treatment number of
*
sample a nd do se Sex Observation time Number % lung tumors Histological types
Untreated:
No dose M Died after 17 months 0/32 0
No dose F Died after 17 months 1/20 5 1 1 adenoma
Quartz
(Min-U-Sil 5):
12-mg dose M Sacrificed at 11 months 3/18 17 37 6 adenomas, 25 adeno-
Sacrificed at 17 months 6/19 32 carcinomas, 1 undifferen-
Died after 17 months 12/14 86 tiated carcinoma, 2 mixed
carcinomas, and 3 epi-
dermoid carcinomas
12-mg dose F Sacrificed at 11 months 8/19 42 59 2 adenomas, 46 adeno-

Sacrificed at 17 months 10/17 59 carcinomas, 3 undifferen-
Died after 17 months 8/9 89 tiated carcinomas, 5 mixed
carcinomas, and 3 epi-
dermoid carcinomas
20-mg dose F Died after 17 months 6/8 75 13 1 adenoma, 10 adeno-

carcinomas, 1 mixed
carcinoma, and 1 epi-
dermoid carcinoma
Quartz (hydrogen
fluoride-etched
Min-U-Sil 5):
12-mg dose M Sacrificed at 11 months 2/18 11 20 5 adenomas, 14 adeno-

Sacrificed at 17 months 7/19 37 carcinomas, and 1 mixed
Died after 17 months 7/9 78 carcinoma
12-mg dose F Sacrificed at 11 months 7/18 39 45 1 adenoma, 36 adeno-

Sacrificed at 17 months 13/16 81 carcinomas, 3 mixed
Died after 17 months 8/8 100 carcinomas, and 5 epi-
dermoid carcinomas
Sources: Saffiotti et al. [1993; 1996].
*
As mg quartz suspended in 0.3 ml saline.
Number of rats with lung tumors per number of rats observed.
At all observation times.

Although new long-term carcinogenesis in vitro studies are needed to develop effec-
studies in animals may provide information tive cellular and molecular models of
about dose-response relationships and inhi- carcinogenesis [Holland 1995; Saffiotti et al.
bition of quartz toxicity or reactivity in vivo, 1996].

5 Conclusions
The following conclusions about the health workers [Steenland and Stayner 1997]
effects caused by exposure to respirable and higher summary relative risks of 2.2
crystalline silica are derived from studies in to 2.8 for silicotic workers [Steenland
humans and animals published since the 1974 and Stayner 1997; Tsuda et al. 1997;
criteria document [NIOSH 1974]. These Smith et al. 1995]. Some of the studies
studies support the risk of silicosis, lung of silica-exposed workers controlled for
cancer, and several other debilitating and fatal the effects of smoking and others did
diseases from occupational exposure to not. The available data also support the
crystalline silica. The onset of silicosis and conclusion that silicosis produces an in-
lung cancer is thought to be related to the creased risk for bronchogenic carci-
biological activity and the lack of solubility of noma, but the data are less clear as to
crystalline silica particles in body fluids and whether silica exposure is associated with
tissues. lung cancer in the absence of silicosis
[ATS 1997].
5.1 Lung Cancer
In 1988 testimony to the U.S. Department of 5.2 Noncarcinogenic
Labor, NIOSH recommended that respirable Health Effects
crystalline silica be considered a potential
occupational carcinogen [54 Fed. Reg. 2521 In 1974, NIOSH established an REL for
(1989)]. Since then, additional studies have respirable crystalline silica of 0.05 mg/m3 as a
supported a lung cancer risk from exposure to 10-hr TWA to prevent the risk of silicosis from
crystalline silica: occupational exposure [NIOSH 1974]. Since
then, additional studies have indicated that a
Lung cancer is associated with occupa- risk for silicosis exists at the NIOSH REL.
tional exposures to crystalline silica Three recent epidemiologic studies have
[ATS 1997], specifically quartz and shown that the estimated risk of silicosis for a
cristobalite [IARC 1997]. 45-year working lifetime is 47% to 90% for
cumulative silica exposures at concentra-
An exposure-response relationship has tions equal to the current OSHA and MSHA
been reported in studies of miners, dia- PELs, and approximately 10% to 30% at
tomaceous earth workers, granite work- concentrations equal to the NIOSH REL (see
ers, pottery workers, refractory brick appendix) [Kreiss and Zhen 1996; Steenland
workers, and other workers (see Section and Brown 1995a; Hnizdo and Sluis-Cremer
3.4.2). 1993]. The results from these studies support
the need for continued medical and epide-
Meta-analyses of the epidemiologic miologic surveillance of workers after they
studies of silica exposure and lung can- leave employment and for revision of OSHA
cer reported a moderate summary rela- and MSHA standards for respirable crystalline
tive risk of 1.3 for silica-exposed silica.

5 CONCLUSIONS
Additional studies have reported the risk for 5.3 Exposures, Monitoring,
several other debilitating and fatal diseases: and Controls
Several epidemiologic studies have re- Published studies on workers exposed to

ported statistically significant numbers crystalline silica indicate that exposures still
of excess deaths or cases of immuno- occur at concentrations exceeding the OSHA
logic disorders and autoimmune dis- and MSHA PELs and the NIOSH REL.
eases in silica-exposed workers. These Engineering control methods used to control
diseases and disorders include sclero- silica exposures in some industrial environ-
derma [Steenland and Brown 1995b; ments may not be feasible for reducing
Cowie 1987], rheumatoid arthritis airborne exposures in other workplaces where
[Sluis-Cremer et al. 1986; Klockars et al. their implementation is hindered by the type of
1987; Rosenman and Zhu 1995], sys- work being performed. In addition, sampling
temic lupus erythematosus [Steenland and analytical techniques used to measure
and Brown 1995b], and sarcoidosis airborne crystalline silica exposures are
[Rafnsson et al. 1998]. limited in their ability to accurately quantify
exposures below the NIOSH REL. The
following issues must be resolved to prevent
Recent epidemiologic studies have re- silicosis and other debilitating and fatal
ported statistically significant associa- diseases:
tions of occupational exposure to crys-
talline silica with renal diseases and
subclinical renal changes [Steenland et
Many occupational exposures to crystal-
line silica still exceed applicable Federal
al. 1990, 1992; Steenland and Brown
standards. Of the 255 industries targeted
1995b; Calvert et al. 1997; Nuyts et al.
for OSHA inspection between 1980 and
1995; Hotz et al. 1995; Boujemaa et al.
1992, 48% had overall average expo-
1994; Ng et al. 1993].
sures for respirable quartz that exceeded
the PEL [Freeman and Grossman 1995].
Crystalline silica may affect the immune Analysis of OSHA compliance data for
system, leading to mycobacterial infec- five of the three-digit SICs (masonry and
tions (tuberculous and nontuberculous) plastering, heavy construction, painting
or fungal infections [ATS 1997; NIOSH and paper hanging, iron and steel found-
1992a,b, 1996b; Ziskind et al. 1976; ries, and metal services) for the period
Parkes 1982; Parker 1994], especially in 19791995 indicated that an estimated
workers with silicosis [Corbett et al. number of workers were exposed to con-
1999; Kleinschmidt and Churchyard centrations of respirable crystalline sil-
1997; Althouse et al. 1995; Goldsmith ica that were at least 10 times the NIOSH
et al. 1995; Hnizdo and Murray 1998; REL of 0.05 mg/m3 (10-hr TWA) [Linch
ATS 1997]. et al. 1998] (see Section 2.3).
Occupational exposure to respirable cry- Workers are exposed to crystalline silica

stalline silica is associated with bron- in a variety of industries and occupations
chitis, COPD, and emphysema (see Sec- in which engineering controls may not
tion 3.5). Some epidemiologic studies be feasible for reducing exposures and
suggest that these health effects may be may necessitate the use of other worker
less frequent or absent in nonsmokers. protection measures such as substitution

5 CONCLUSIONS
(use of a less hazardous material) or res- Until these improved sampling and
pirator use. analytical methods are developed for
respirable crystalline silica, NIOSH will
Current sampling and analytical meth- continue to recommend an exposure limit
ods used to evaluate occupational expo- of 0.05 mg/m3 to reduce the risk of
sure to crystalline silica do not meet the developing silicosis, lung cancer, and
appropriate accuracy criterion needed to other adverse health effects. NIOSH also
quantify exposures at concentrations be- recommends minimizing the risk of
low the NIOSH REL of 0.05 mg/m3 (see illness that remains for workers exposed
Section 2.4). However, the recent intro- at the REL by substituting less hazardous
duction of a new sampler that can operate materials for crystalline silica when
at a higher flow rate and the ongoing im- feasible, by using appropriate respiratory
provements in the analysis of crystalline protection when source controls cannot
silica should soon make it possible to keep exposures below the NIOSH REL,
measure crystalline silica exposure accu- and by making medical examinations
rately when it is below 0.05 mg/m3. available to exposed workers.

6 Research Needs
6.1 Health-Related Research C crystalline silica compared with
crystalline glass, amorphous sili-
The relationship of occupational crystalline cone, and silicates [Craighead 1996]
silica exposure with silicosis and other silica-
related diseases is well documented in the lit- C crystalline silica compared with sub-
erature. However, the mechanisms and particle stitute materials for abrasive blasting
characteristics that cause silicosis and other and other tasks that use crystalline
silica-related diseases have not been precisely silica
defined. Prevention of silicosis, lung cancer,
and other silica-related diseases can be facili-
tated by the following: C dust mixtures that contain crystalline
silica [Craighead 1996; Donaldson
and Borm 1998; Dufresne et al.
Development of methods for earlier de- 1998]
tection or more definitive noninvasive
evaluation of silica-related pulmonary
disease, such as methods to improve the C quartz contaminated with trace ele-
sensitivity of radiography for detecting ments [Castranova et al. 1997]
silicosis (these methods were reviewed
by Wilt et al. [1998] and Talini et al. The association of surface properties of
[1995]) silica particles with specific work pro-
cesses and health effects
Further in vitro and in vivo studies of
mechanisms for development of Cellular, molecular, and animal models
of silica carcinogenesis to explore
C silicotic nodules [Craighead 1996] whether silica dust is an initiator or a
promoter of lung cancer [Craighead
1996] and to evaluate a dose-response
C autoimmune diseases relationship
C DNA damage by silica particles Animal models of individual suscepti-

[Saffiotti et al. 1994] bility and the development of fibrosis
[Craighead 1996], including the translo-
Further in vitro and in vivo studies of the cation of silica particles from the lungs
toxicity and pathogenicity of [Adamson and Prieditis 1998]
C alpha quartz compared with its poly- Animal models of the adverse effects of
morphs [Craighead 1996] crystalline silica on the kidneys and liver

6 RESEARCH NEEDS
Routes and kinetics of lymphatic trans- Gather prevalence, incidence, and mor-
port and deposition of silica particles tality data about silica-related diseases
[Craighead 1996] such as cancer, scleroderma and other
autoimmune diseases, nonmalignant re-
Further epidemiologic studies and surveillance nal disease, and other adverse health ef-
of silica-exposed workers are needed to do the fects to assess morbidity and mortality
following: risk factors and to identify areas where
preventive measures could be imple-
Determine the exposure-response rela- mented
tionship between occupational silica
dust exposure and lung cancer in non- Determine whether silicosis or silica-
smokers related lung cancers are related to a spe-
cific gene, gene pattern, or other individ-
Determine why lung cancer risks appear ual susceptibility factors
to be higher in silicotic workers (e.g., de-
termine the histologic type and anatomic Improve the methods for estimating his-
location of lung cancers in workers with torical exposures for retrospective co-
and without silicosis [Ducatman et al. hort studies
1997])
Improve the assessment of potential
Evaluate exposure-response relation- confounding and synergistic effects of
ships between occupational silica dust smoking in silica-exposed workers
exposure and (1) TB [ATS 1997] and [Checkoway 1995]
(2) changes in cellular components
(lymphocytes, Clara cell protein) or im- Improve the assessment of potential
munoglobulin concentrations confounding and synergistic effects of
other carcinogens present in the work
Determine the relationship between oc- environment of silica-exposed workers
cupational exposure to silica dust and [Dufresne et al. 1998]
C TB in silica-exposed workers without Determine whether adverse health ef-

diagnosed silicosis fects are associated with occupational
exposure to materials that could be sub-
C clinically significant changes in the stitutes for crystalline silica [NIOSH
lung function of nonsmokers 1992a]
C emphysema in nonsmokers
6.2 Research Related to
C gastric cancer and other nonpulmo-
nary cancers Exposure Measurement
Reducing the OSHA and MSHA PELs for
Gather uniform national and interna- crystalline silica to concentrations below the
tional prevalence and incidence data NIOSH REL (0.05 mg/m3 for up to a 10-hr
about silicosis cases to identify indus- workday during a 40-hr workweek) would re-
tries, occupations, and work areas where quire new methods that can accurately mea-
preventive measures could be imple- sure low airborne concentrations at the
mented [CSTE 1996; Wagner 1997] NIOSH accuracy criterion. (Limitations of

6 RESEARCH NEEDS
current NIOSH methods for measuring worker Further research to validate the feasibil-
exposure to airborne crystalline silica are dis- ity of on-filter analysis under field
cussed in Chapter 2). Such new methods will conditions (preliminary investigation of
depend on the following types of research and particle transition between the cyclone
development: and the sample collection cassette indi-
cates that it is possible to improve the
Reevaluation of the 10-mm nylon cy- uniformity of particles deposited on the
clone, the GK2.69 cyclone, or other pro- filter to permit an accurate on-filter anal-
posed devices at exposure concentra- ysis)
tions below 0.05 mg/m3
Collaborative testing of any improved or
Ascertainment of the sampling effi- new sampling and analytical methods to
ciency of proposed samplers versus par- demonstrate equivalence
ticle aerodynamic diameter
Side-by-side comparison of proposed 6.3 Research Related to the

samplers under field conditions
Control of Exposure
Development of samplers that can oper- Protecting workers from crystalline silica ex-
ate at higher flow rates than those cur- posures can be accomplished through a num-
rently available ber of means. Respiratory protection and ad-
ministrative controls are important means of
Development of working standards that protecting workers, but they should not be used
use different types of filter media (e.g., as the primary method of preventing worker
PVC) to reduce errors in calibration exposure. Other exposure control methods (in-
cluding process modifications to eliminate
Further improvement of the system used hazards, substitution, and engineering con-
to produce replicate crystalline silica trols) should be the primary focus of any safety
samples for the PAT Program* to and health program in preventing occupational
exposures. For some industries, research is
C improve the reproducibility of inter-
needed to develop cost-effective controls;
laboratory results for silica analysis,
whereas in other industries, work is needed to
C eliminate problems with sample over- increase the availability and use of control
loading, and measures and to explore barriers that prevent
the introduction of control technology. Spe-
C determine how to account for bias be- cific types of research are needed in the follow-
tween results from different analyti- ing industries:
cal methods
Construction. The construction industry
presents a major challenge for protecting
workers. In this industry, crystalline sil-
*
This system has undergone improvements from its orig- ica is present in many of the building
inal form to reduce the intersample variability. Cur- materials and construction substrates
rently, intersample CV is on the order of 0.08 to 0.12.
Only cursory testing of these improvements has been (i.e., rock and soil). Silica sand is a ma-
carried out, and further improvements may be neces- jor component of concrete and mortar
sary. and is used in the production of brick

6 RESEARCH NEEDS
and concrete masonry units. In addition concrete forms can be used to impart
to the ubiquitous presence of silica in smoother surface finishes and reduce
construction, this industry also faces a the need for additional grinding or
challenge from the ever-changing nature rework. Additional research is needed
of the worksite. These changes create to investigate alternative methods for
two problems in the control of silica ex- blowing and sweeping on construc-
posures. First, permanent control mea- tion sites (e.g., the use of vacuums
sures are not feasible for many worksites instead of compressed-air lances to
because of the short duration of the task remove debris from cracks in road
(e.g., concrete cutting or coring opera- construction).
tions). Second, the manner in which the
work is performed at a worksite can cre-
Foundries. Foundries use large volumes
ate a silica exposure for workers at adja-
of sand in the molds and the cores to pro-
cent worksites. Control methods such as
duce castings. In general, foundries that
wet cutting of bricks and concrete ma-
cast higher-temperature metals (steel,
sonry units and use of high-velocity/
gray iron, and stainless steel) have the
low-volume (HVLV) ventilation sys-
potential for creating higher silica expo-
tems during cutting and grinding of con-
sures than foundries that cast lower-
crete have been effective in reducing ex-
temperature metals (aluminum, brass,
posures to silica at some worksites.
and bronze). The molding sand used in
However, the following research is
most foundries contains a small percent-
needed to improve these techniques and
age of water and other binders. High
the feasibility of their use:
temperatures dry the sand, making it
more likely to become airborne. Various
C The use of water is not a feasible con- types of controls are being used in
trol method for reducing exposures foundries, but additional research is
on many interior jobs or in cold tem- needed:
peratures. Research is needed to find
methods for increasing (1) the appli-
cability of water to more operations C Alternative processes such as the lost
and (2) the use of water in applica- foam casting process have been used
tions where it is considered feasible. for some metal castings, but they re-
quire additional investigation to de-
C The use of HVLV ventilation in- termine whether they can effectively
volves problems such as insufficient reduce exposures by minimizing the
hood capture velocity, obstruction of amount of casting cleaning and sand
the work area by the control, and handling required to produce high-
poor dust collector performance. Re- quality castings.
search is needed to improve the per-
formance of HVLV systems and the C Industrial ventilation is widely used
feasibility of their use in other opera- to capture and contain silica-contain-
tions. ing aerosols. However, its effective-
ness is only as good as its design, in-
C Alternative materials and work stallation, and maintenance. Research
methods can be used to reduce crys- is needed on methods for effectively
talline silica exposures. For example, communicating the need for routine

6 RESEARCH NEEDS
and proper maintenance of ventila- exposures associated with silica-con-

tion systems. taining substrates.
C Automated processes in foundries Surface and other mining. Technology

need to be explored so that workers exists in the surface mining industry to
can be removed from operations that control exposure to crystalline silica.
generate high silica exposures. However, silicosis persists because con-
trols are often not implemented or prop-
erly maintained [NIOSH 1996b]. Effec-
C The use of HVLV ventilation sys- tive methods are needed for informing
tems during casting cleaning needs drillers and drill owners about the need
to be evaluated. for continued maintenance and proper
use of dust controls on drills. Mine
C Alternative methods should be in- workers at other than surface sites have
vestigated for blowing and sweeping silica exposures that have not been well
in foundries. Vacuums may be feasi- characterized. For example, little or no
ble as an alternative to compressed- information is available about dust con-
air lances and dry sweeping. trol measures for hard-rock tunneling
operations. Research is needed to deter-
mine which control measures provide
Abrasive blasting operations. Abrasive the best protection and are feasible to
blasting operations have been docu- implement.
mented to generate some of the highest
crystalline silica exposures. Other blast- Paints, coatings, glass, cosmetics, plas-
ing materials such as steel shot, steel tics, and cleaning products. Crystalline
grit, and boiler slag have been used as silica is used in a diverse number of pro-
substitutes for silica sand. However, ad- ducts, including paints, coatings, glass,
ditional research is needed to determine cosmetics, plastics, and cleaning prod-
the safety of substitute blasting materi- ucts. However, the hazards associated
als. In addition, replacing silica sand with silica exposure are often not recog-
with a substitute blasting material will nized in these industries. Research is
not eliminate silica exposures when needed to develop methods for commu-
blasting on silica substrates such as con- nicating hazards and controls to workers
crete or granite. Many of these opera- and employers. The need is for innova-
tions may be modifiable to reduce the tive technologies that can be transferred
amount of blasting required. Additional across industries. Additional research is
research is needed on alternative blast- needed to investigate the feasibility of
ing methods such as high-pressure water using HVLV ventilation systems and
jetting, slurry blasting, and vacuum water to reduce exposures in these in-
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Appendix
Occupational Exposure Limits
Table A1. U.S. guidelines and limits for occupational exposure to crystalline silica
Reference Substance Guideline or limit (mg/m 3)
NIOSH [1974] Crystalline silica:* quartz, cristobalite, and REL = 0.05 (for up to a 10-hr workday
tridymite as respirable dust during a 40-hr workweek)
OSHA [29 CFR Respirable crystalline silica, quartz PEL = 10 % quartz + 2 (8-hr TWA)
1910.1000Table Z-3] Respirable crystalline silica, cristobalite PEL = half of the value calculated from
the formula for quartz
Respirable crystalline silica, tridymite PEL = half of the value calculated from
the formula for quartz
MSHA [30 CFR 56, 57, Respirable quartz in underground and surface PEL = 10 % quartz + 2 (8-hr TWA)
70, 71] metal and nonmetal mines
Respirable crystalline silica present in RDS = 10 % quartz (8-hr TWA)
concentrations >5% in surface and
underground coal mines
ACGIH [2001] Respirable crystalline silica, quartz TLV = 0.05 (8-hr TWA)
Respirable crystalline silica, cristobalite TLV = 0.05 (8-hr TWA)
Respirable crystalline silica, tridymite TLV = 0.05 (8-hr TWA)
Adapted from Hearl [1996].

*
Identified by NIOSH as a potential occupational carcinogen [54 Fed Reg. 2521 (1989)].
Abbreviations: REL = recommended exposure limit; PEL = permissible exposure limit;

RDS = respirable dust standard; TLV = threshold limit value; TWA = time-weighted average.

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NIOSH HAZARD REVIEW

Health Effects of Occupational

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Telephone: 180035NIOSH (18003564674)

or visit the NIOSH Web site at www.cdc.gov/niosh

DHHS (NIOSH) Publication No. 2002129

Kathleen M. Rest, Ph.D., M.P.A.

2 Properties, Production, and Potential for Exposure . . . . . . 4

2.4.1 Sampling Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

3 Human Health Effects . . . . . . . . . . . . . . . . . . . . 21

3.3 TB and Other Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

3.5 Other Nonmalignant Respiratory Diseases and Related Conditions . . . . . . . 51

3.6 Autoimmune and Chronic Renal Diseases . . . . . . . . . . . . . . . . . . . . 67

Nontuberculous mycobacteria: Mycobacteria species other than the Mycobacterium tuberculosis

Sarcoidosis: A rare multisystem granulomatous disease characterized by alterations in the immune

Scleroderma (progressive systemic sclerosis): A rare multisystem disorder characterized by in-

NIOSH also appreciates the comments of the following external reviewers:

William Beckett, M.D., M.P.H. Jeffrey Gift, Ph.D.

Gerald S. Davis, M.D. Eva Hnizdo, Ph.D.

Allen G. Macneski John A. Ulizio

Michelle Schaper, Ph.D. James L. Weeks, Sc.D.

2 Respirable Crystalline Silica

Respirable Crystalline Silica 3

4 Respirable Crystalline Silica

Estimated number of % total

734 Services to dwellings and other buildings 65,812 10.3

327 Concrete, gypsum , and p laster products 63,456 33.3

176 Roofing and sheet metal work 51,153 25.3

356 General industrial machinery and equipment 44,991 16.2

807 Medical and dental laboratories 37,063 30.0

179 Miscellaneous special trade contractors 32,615 7.8

753 Automotive repair shops 30,826 7.1

326 Pottery and related products 29,772 81.7

13 Oil and gas extraction 408,175 100

12 Bituminous coal and lignite mining 174,131 100

14 Mining and qua rrying of nonme tallic minerals,

10 Metal mining 39,856 100

Source: NIOSH [1991].

Exposure is assumed to be 100% in the mining industries.

Respirable Crystalline Silica 5

6 Respirable Crystalline Silica

Industry or activity Oper ations and tasks Sou rce m aterials

Agriculture Plowing, harvesting, using machine ry, Soil

Construction Abrasive blasting of structures and Sand , concrete, rock, soil,

Cement Raw material processing Clay, sand, limestone,

Abrasives Silicon carbide production, abrasive Sand, tripoli, sandstone

Respirable Crystalline Silica 7

Industry or activity Oper ations and tasks Sou rce m aterials

8 Respirable Crystalline Silica

Gen eral use End use

Metallurgical work Silicon carbide, flux for metal smelting

Fillers Rub ber, p aints, putty, whole grain fillers/building p roducts

Ceramics Pottery, brick, tile

Filtration W ater (municipal, county, local), swimming pool, others

Petroleum manufacturing Hydraulic fracturing, well packing, and cementing

Gravel Silicon, ferrosilicon, filtration, nonmetallurgical flux, other

Sources: IARC [1997]; BOM [1994].

Respirable Crystalline Silica 9

COC Occupation Number %

616 Mining machine operator 39 16.0

889 Laborer, except construction 29 11.9

019 Manager or administrator, not elsewhere classified 11 4.5

633 Supervisor or precision production occupations 11 4.5