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AFLATOXINS
FOOD SOURCES, OCCURRENCE
AND TOXICOLOGICAL EFFECTS
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FOOD SCIENCE AND TECHNOLOGY
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FOOD SCIENCE AND TECHNOLOGY
AFLATOXINS
FOOD SOURCES, OCCURRENCE
AND TOXICOLOGICAL EFFECTS
ADINA G. FAULKNER
EDITOR
New York
Copyright 2014 by Nova Science Publishers, Inc.
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CONTENTS
Preface vii
Chapter 1 Bio-Prevalence, Determination and Reduction
of Aflatoxin B
1
in Cereals 1
Jelka Pleadin, Ksenija Markov, Jadranka Frece,
Ana Vuli and Nina Peri
Chapter 2 Aflatoxin Occurrence 35
Elham Esmaeilishirazifard and Tajalli Keshavarz
Chapter 3 Aflatoxins in Food and Feed: Contamination
Exposure, Toxicology and Control 63
Marta Herrera, Antonio Herrera and Agustn Ario
Chapter 4 Immunosuppressive Actions of Aflatoxin
and Its Role in Disease Susceptibility 91
Johanna C. Bruneau, Orla Hayden,
Christine E. Loscher and Richard OKennedy
Chapter 5 Aflatoxins Hazards and Regulations Impacts
on Brazil Nuts Trade 107
Otniel Freita-Silva, Renata Galhardo Borguini
and Armando Venncio
Contents vi
Chapter 6 Polymorphisms of DNA Repair Genes
and Toxicological Effects of Aflatoxin
B
1
Exposure 125
Xi-Dai Long, Jin-Guang Yao, Qian Yang,
Cen-Han Huang, Pinhu Liao, Le-Gen Nong,
Yu-Jin Tang, Xiao-Ying Huang, Chao Wang,
Xue-Ming Wu, Bing-Chen Huang, Fu-Zhi Ban,
Li-Xia Zeng, Yun Ma, Bo Zhai, Jian-Jun Zhang,
Feng Xue, Cai-Xia Lu and Qiang Xia
Chapter 7 Incidence of Aspergillus Section Flavi
and Interrelated Mycoflora in Peanut
Agroecosystems in Argentina 157
Mara Alejandra Passone, Andrea Nesci,
Anala Montemarani and Miriam Etcheverry
Chapter 8 Toxicological Effects, Risk Assessment and
Legislation for Aflatoxins 191
Marina Goumenou, Dimosthenis Axiotis,
Marilena Trantallidi, Dionysios Vynias,
Ioannis Tsakiris, Athanasios Alegakis,
Josef Dumanov and Aristidis Tsatsakis
Chapter 9 Food Sources and Occurrence of Aflatoxins:
The Experience in Greece 233
Ioannis N. Tsakiris, Elisavet Maria Renieri,
Maria Vlachou, Eleftheria Theodoropoulou,
Marina Goumenou and Aristides M. Tsatsakis
Chapter 10 Aflatoxins As Serious Threats to Economy and Health 259
Lipika Sharma, Bhawana Srivastava, Shelly Rana,
Anand Sagar and N. K. Dubey
Index 287
PREFACE
Progress in understanding the biology of Aspergillus has greatly improved
with the new techniques in genome sequencing and the developed molecular
tools that enable rapid genetic analysis of individual genes. Particularly, the
genetics of aflatoxin synthesis is regarded as a model to gain insight into
fungal secondary metabolism. This compilation discusses topics that include
the prevalence of aflatoxin B1 in cereals; contamination exposure, toxicology
and control of aflatoxins in food and feed; immunosuppressive actions of
aflatoxin; hazards and regulations; toxicological effects, risk assessment and
legislation for aflatoxins; and the threat aflatoxins have on the economy and
health.
Chapter 1 - Moulds of Aspergillus genus are among the most important
causes of food and feed spoilage and can produce mycotoxins as toxic
secondary metabolites when under adverse conditions. Aflatoxins are a group
of mycotoxins that commonly contaminate maize and groundnuts, and are
categorized by the International Agency for Research on Cancer under Class
1A human carcinogens. From the food safety standpoint, one of the most
important mycotoxins is aflatoxin B
1
(AFB
1
). Due to its potent carcinogenic,
teratogenic and mutagenic effects dependent on the level and length of
exposure, the presence of this contaminant in food and feed should be kept as
low as achievable. In order to investigate the occurrence of AFB
1
, determine
its concentrations and explore the possibility of its reduction using different
methods, samples of maize, wheat, barley and oat were collected from
different cultivation fields during a three-year period. The immunoassay
(ELISA) as a screening method and high performance liquid chromatography
tandem mass spectrometry (LC-MS/MS) as a confirmatory method were used
to determine AFB
1
concentrations. Maize contamination seen with AFB
1
Adina G. Faulkner viii
concentrations higher than permitted was associated with climate conditions
established in the period of concern, which was extremely warm and dry, and
might had favored mould production and AFB
1
formation. Substantial to
almost absolute AFB
1
reduction in the maize samples was achieved using
gamma radiation. A strong antifungal effect was also obtained upon the use of
essential oils and lactic acid bacteria as biological AFB
1
-reduction alternatives.
As the presence of AFB
1
in cereals could be dangerous for human and animal
health, in order to prevent its harmful effects and huge economic problems, the
prevention of formation of this contaminant and consistent control over it are
of major interest. Based on these substantiated grounds, possibilities of
implementing new methods of AFB
1
determination and reduction within the
frame of safe food production are virtually countless.
Chapter 2 - Toxigenic fungi in crops have been divided historically into
two groups, field and storage fungi. Mycotoxins are produced by toxigenic
fungi at the fields and in the storage. Although many compounds are termed as
mycotoxin, there are only five agriculturally-important fungal toxins:
deoxynivalenol, zearalenone, ochratoxin A, fumonisin and aflatoxin.
Penicillium and Aspergillus species are the most important storage fungi.
However, they can also invade stressed plants in the field. The main
mycotoxins produced by Aspergillus species are aflatoxins, citrinin and
patulin. The word aflatoxin comes from Aspergillus flavus toxin, based on
the fact that A. flavus and A. parasiticus are the predominant species
responsible for aflatoxin contamination of crops prior to harvest or during
storage. Aflatoxins B1, B2, G1, and G2 are the four major isolated aflatoxins
from food and feed commodities.
A. flavus and A. parasiticus have distinct affinity for nuts and oilseeds
including peanuts, maize and cotton seed. Cereals are a general substrate for
growth of A. flavus but, unlike nuts, small grain cereal spoilage by A. flavus is
the result of poor handling. Moreover, aflatoxin M1 as a milk contaminant has
potential risk for animal and human health. The character of the aflatoxin
problem varies by region. For instance, aflatoxin accumulation in stored maize
in subtropical Asia has risen rapidly in post-harvest conditions whereas in the
US, the issue is pre-harvest condition of maize. Therefore, the exposure to
aflatoxins differs between countries particularly due to different diets. Food
contamination with Aspergillus is associated with warm and dry climates.
However, in variable environmental conditions, the aflatoxin contamination
may differ from one year to another at the same location.
Progress in understanding the biology of Aspergillus has greatly improved
with the new techniques in genome sequencing and the developed molecular
Preface ix
tools that enable rapid genetic analysis of individual genes. Particularly, the
genetics of aflatoxin synthesis is regarded as a model to gain insight into
fungal secondary metabolism. Well-designed research on production of the
aflatoxin precursor sterigmatocystin with the genetic model A. nidulans, has
contributed greatly to our knowledge of the aflatoxin pathway and the global
regulatory mechanisms. According to the recent studies, fungal pathogenesis is
related to lipid-mediated fungal-host crosstalk, suggesting that secondary
metabolism may be controlled by oxylipins at the transition level. Also, some
oxylipins have been reported to be engaged in the signalling mechanism like
quorum sensing responses in Aspergillus. Quorum sensing molecules and their
genes which are responsible for intra and inter kingdom communications could
be applied in the future aflatoxin bio-control strategies.
Chapter 3 - Aflatoxins (AFs) are secondary metabolites produced by
various fungal species of the genus Aspergillus such as Aspergillus flavus and
Aspergillus parasiticus. The most important compounds are aflatoxins B1, B2,
G1 and G2, as well as two metabolic products secreted in milk, M1 and M2.
The worldwide occurrence of aflatoxins contamination in raw agricultural
products has been well documented; such contamination occurs in a variety of
food and feed, such as cereals, nuts, dried fruits, spices and also in milk as a
consequence of the ingestion of contaminated feed. However, pistachios,
peanuts and corn are the most frequently contaminated food items reported in
the Rapid Alert System for Food and Feed (RASFF) of the European Union.
The occurrence of aflatoxins is mainly affected by environmental factors such
as climatic conditions, geographic location, agricultural practices, and
susceptibility of the products to fungal growth during harvest, storage and
processing. High contamination levels of aflatoxins are mainly associated with
post-harvest growth of Aspergillus moulds in poorly stored commodities.
Aflatoxins can cause adverse effects to the health of animals and humans.
These toxins have been reported to be associated with acute liver damage,
liver cirrhosis, induction of tumors and teratogenic effects. Aflatoxin B1
(AFB1) is usually predominant and the most toxic among aflatoxins because it
is responsible for hepatocarcinoma in animals and strongly associated with the
incidence of liver cancer in humans. AFB1 is a genotoxic and mutagenic
chemical, and it has been classified by the International Agency of Research
on Cancer (IARC) as human carcinogen (group 1). The toxic effects of the
ingestion of aflatoxins in both humans and animals depend on several factors
including intake levels, duration of exposure, metabolism and defense
mechanisms, and individual susceptibility. Aflatoxins affect not only the
health of humans and animals but also the economics of agriculture and food.
Adina G. Faulkner x
Because of the multiple adverse health effects to humans and animals
caused by aflatoxin consumption, many nations worldwide have regulatory
standards on aflatoxin in food and feed. The European Union (EU) regulation
on aflatoxins in foodstuffs is among the strictest in the world (Commission
Regulation (EC) n 1881/2006 and successive amendments). Maximum
contents of aflatoxins in feeds are also established by Commission Regulation
(EU) n 574/2011 on undesirable substances in animal feed.
Throughout the world there are many advisory bodies concerned with
food safety, including the World Health Organization (WHO), the Food and
Agriculture Organization of the United Nations (FAO), the Codex
Alimentarius Joint Expert Committee for Food Additives and Contaminants
(JECFA), and many others, which regularly assess the risk from mycotoxins,
advise on controls to reduce consumer exposure and establish different
regulations for these toxins in different countries.
Chapter 4 - Aflatoxins are secondary metabolites produced by fungi of the
Aspergillus species. They occur as contaminants in a variety of food and feed
stuffs that have been infected with the producing fungi. Aflatoxin exposure is
known to cause a number of acute and chronic effects in both humans and
animals, including immunosuppression, liver and other cancers, and failure of
vaccination regimens. The immunomodulatory effects of the aflatoxins have
been shown to affect cell-mediated immunity more than humoral immunity. In
particular, aflatoxin exposure modulates secretion of inflammatory cytokines
and phagocytic function. Decreases in phagocytosis and inflammation
observed following aflatoxin exposure may reduce the effectiveness of the
host immune response to infection, thereby increasing susceptibility to
infection in individuals exposed to these toxins. The aim of this chapter is to
summarise the immunomodulatory effects of aflatoxin exposure in order to
better understand its potential immunosuppressive effects in humans and
animals. The relationship between these immunosuppressive actions and
susceptibility to infection will also be discussed.
Chapter 5 - Brazil nut is an important non-timber forest product produced
in Amazon region. This nut is used as food with high value in the international
market, due to its high nutritional and flavor characteristic and to their
association with environmental conservation and alleviation of poor people
living from Amazonia. Annually, several hundred tons of Brazil nuts are
produced in Brazil. However, they are susceptible to aflatoxins (AF)
contamination. Because of the detection of unacceptable level of AF in Brazil
nuts consignments arriving in European Union ports, in 2003, special
conditions were imposed on Brazil nuts entering the European Union,
Preface xi
decreasing the acceptable levels of AF. In 2010, the European Union revised
AF regulation on nuts; these new limits are more adequate when considering
the complexity of Brazil nut chain and the low risk related to its low
consumption. This chapter points data on the occurrence of AF in Brazil nuts,
as reported by the Rapid Alert System for Food and Feed (RASFF), and
evaluates the efforts made by all sectors involved in the agribusiness of Brazil
nuts, in Brazil, in order to contribute to protection of both domestic and
international consumers from possible health hazard caused by AF.
Chapter 6 - Aflatoxin B
1
(AFB
1
) is an important genic toxin produced by
the moulds Aspergillus parasiticus and Aspergillus flavus. AFB
1
is
metabolized by cytochrome P450 enzymes to its reactive form, AFB
1
-8,9-
epoxide (AFB
1
-epoxide), which covalently binds to DNA and induces DNA
damage. DNA damage induced by AFB
1
, if not repaired, may cause such
genic tox toxicological Effects as DNA adducts formation, gene mutations and
hepatocellular carcinoma (HCC). During the repair process of DNA damage
produced by AFB
1
, DNA repair genes play a central role, because their
function determines DNA repair capacity. In this study, the authors
investigated the association between seven polymorphisms (including rs25487,
rs861539, rs7003908, rs28383151, rs3734091, rs13181, and rs2228001) in
DNA repair genes XPC, XRCC4, XRCC1, XRCC4, XPD, XRCC7, and
XRCC3, and toxicological effects of AFB
1
using a hospital-based case-control
study. Toxicological effects of AFB
1
were analyzed by means of the levels of
AFB
1
-DNA adducts, the mutant frequency of TP53 gene, and the risk of
AFB
1
-related HCC. The authors found that the mutants of XPC, XRCC4,
XRCC1, XRCC4, XPD, XRCC7, and XRCC3 had higher AFB
1
-DNA adducts
levels, compared with the wilds of these genes (3.276 vs 3.640 mol/mol DNA
for rs25487, 2.990 vs 3.897 mol/mol DNA for rs861539, 2.879 vs 3.550
mol/mol DNA for rs7003908, 3.308 vs 3.721 mol/mol DNA for
rs28383151, 3.229 vs 3.654 mol/mol DNA for rs3734091, 2.926 vs 4.062
mol/mol DNA for rs13181, and 3.083 vs 3.666 mol/mol DNA for
rs2228001, respectively). Furthermore, increasing risk of TP53 gene mutation
and HCC was also observed in these with the mutants of DNA repair genes.
These results suggested that polymorphisms of DNA repair genes might
modify the toxicological effects of AFB.
Chapter 7 - Studies in typical and new Argentinean peanut areas showed
that toxigenic Aspergillus section Flavi strains are widely distributed in soils
and seeds, with high probability of being transferred to the storage ecosystem.
Mycological analyses of soil showed that Aspergillus section Flavi population
were present in the two areas at similar counts (3.2x10
2
cfu g
-1
). Within this
Adina G. Faulkner xii
section, two fungal species were frequently isolated with isolation percentages
of 73 and 90% for A. flavus and of 27 and 9% for A. parasiticus in soil
samples from traditional and new areas, respectively. The percentages of the
different A. flavus phenotypes from both peanut-growing areas showed that L
strains were recovered in the highest percentage and represented 59 and 88%
of the isolates with variable ability to produce aflatoxins (AFs). Peanut kernels
collected at harvest time from different localities of Crdoba and Formosa
provinces showed A. flavus and A. parasiticus contamination. The 42.8 and
70% were classified as type L and the percentages of aflatoxigenic A. flavus
strains were 68.6 and 80.0% in samples from traditional and recent peanut-
growing areas, respectively. Highly toxigenic A. flavus S strains were isolated
with major frequency from soil and kernel samples coming from traditional
peanut-growing area. Aflatoxin contamination was detected in peanut kernels
from typical peanut growing area. Harvested peanut were stored during 5
months in three storage systems (big bags, wagons of conditioning and drying
and stockpiled warehouse) and mycological population succession was
analyzed. Fungal isolation was greater from pod (95%) than from kernel
tissues. The most common fungi identified included Penicillium, Aspergillus,
Eurotium and Fusarium spp. Within Aspergillus genus, the section Flavi had
the greatest mean counts of 1.4x10
4
, 9.4x10
2
, 5.2x10
2
cfu g
-1
for big bags,
wagon and warehouse, respectively. A. flavus and A. parasiticus strains with
variable ability to produce AFs were isolated from peanut kernels stored in the
three systems at all sampling periods in the order of 1.5x10
2
, 2.3x10
2
and 4.5
cfu g
-1
, respectively. .A. flavus S and L strains contributed to silo community
toxigenicity during all storage period. Total AF levels ranging from 1.1 to
200.4 ng g
-1
were registered in peanuts conditioned at the higher a
W
values
(0.940.84 a
W
) and stored in big bags. Despite the water stress conditions
registered in the stockpiled warehouse throughout the storage period, AFB
1
levels ranging between 2.9 and 69.1 ng g
-1
were registered from the third
sampling.
Therefore, the interaction between biological and abiotic factors and
substrate may promote the Aspergillus contamination and the subsequent AF
accumulation in peanut from sowing to storage, highlighting the need to
promote good practices in order to avoid the risk of these metabolites
contamination in peanut food chain.
Chapter 8 - Aflatoxins are toxic metabolites produced by the fungus
Aspergillus. The main representatives are aflatoxins B1, B2, G1, G2. Their
occurrence in food like nuts, cereals and cereal-derived products is a result of
fungal contamination before harvest and during storage. Milk can also be
Preface xiii
contaminated by aflatoxin M1 (main metabolite of B1) as a result of animals
exposure to feed contaminated by the aflatoxin B1.
Aflatoxins manifest acute and chronic toxicity. Evidence of acute
aflatoxicosis in humans involving a range of symptoms from vomiting to death
has been reported mainly in Third World Countries. In relation to chronic
toxicity aflatoxins are well known for their genotoxic and carcinogenic
properties while recent studies evident a series of other possible effects like
reprotoxicity, impaired growth in children, intestinal functions, chronic fatigue
syndrome, compromise immunity and interfere with protein metabolism and
multiple micronutrients that are critical to health.
The critical step for aflatoxins risk assessment is the estimation of the real
exposure. For this reason a number of surveys are conducted globally using
tools like biomarkers of exposure and modeling. In addition new parameters
like the climate change are now taken into consideration in order to predict
possible current and future changes of exposure to aflatoxins. As aflatoxins are
compounds of natural origin and their presence in food cannot be totally
eliminated the risk management is based on keeping the total exposure as low
as reasonably achievable taking into account the social-economic impact of
crop and livestock losses. Exposure reduction is achieved mainly by reducing
the number of highly contaminated foods reaching the market by regulatory
control but also applying detoxification strategies. According to the EU
regulatory framework minimization of the exposure to aflatoxins is based on
setting maximum levels of aflatoxins in different foodstuffs (4 10 g/kg total
aflatoxins) and feed (EC/1881/2006, Directive 2002/32/EC). Products
exceeding the maximum levels should not be placed on the EU market.
Methods of sampling and analysis for the official control of aflatoxins, are also
set (EC/401/2006) in order to ensure common sampling criteria to the same
products and that certain performance criteria are fulfilled. The United States
Food and Drug Administration (FDA) has established the action levels for
aflatoxin present in food to the 20 g/kg (0.5 g/kg for milk) and up to 300
g/kg for feed. Finally an action level of 10 g/kg total aflatoxins is also used
from Japan authorities.
Chapter 9 - This paper presents a review of the occurrence of aflatoxins in
different food commodities in Greece, based both on results represented in
literature as well as results derived from monitoring programs of the Center of
Toxicology Science & Research, Medical School, University of Crete.
Aflatoxins, can pose a severe threat to food safety, since they are characterized
carcinogenic to humans, IARC Group 1. They may be formed or developed in
any stage of the agricultural production (primary production, processing and
Adina G. Faulkner xiv
storage) as a result of transitional weather conditions or of poor storage.
Studies, monitoring programs and surveys, which have been carried out in
Greece, are mainly focused in milk and dairy products. In this context, several
studies have been conducted in animal feeds as well, since there is notable
evidence that they are potential sources of aflatoxins in milk production.
Additionally, both black and green olives have been examined for possible
contamination by aflatoxins, due to the fact that they are damaged during
harvest and processing and thus providing a substrate for aflatoxin
development. Finally, a limited number of studies investigate the presence of
aflatoxins in different processed products like breakfast cereals. The above
foodstuffs have been studied on account of their high nutritional value and the
fact that they are consumed by different population groups. Results indicate
that residue levels of aflatoxins which are presented in fresh as well as
processed agricultural products, do not pose any considerable risk for the
Greek population groups. The most important factors influencing the levels of
aflatoxins in major agricultural products appear to be the growing and
cultivation techniques, as well as the food safety parameters during harvesting,
storage and processing. An additional issue, which seems to raise concern
internationally, is the fact that climate change in combination with
modifications in the cultivation techniques may affect the frequency and
severity of aflatoxin residues in agricultural products.
Chapter 10 - This review deals with the aflatoxins especially with their
food sources, wide occurrence and toxicological effects on animals and
humans. Aflatoxins are highly oxygenated, heterocyclic, difuranocoumarin
compounds and are an important group of mycotoxins produced by the fungi.
There are almost 20 different types of aflatoxins identified till now; among
these AFB
1
is considered to be the most toxic. Aflatoxins persist to some
extent in food even after the inactivation of the fungi by food processing
methods, such as ultra-high temperature products, due to their significant
chemical stability. Aflatoxins can affect a wide range of commodities
including cereals, oilseeds, spices, and tree nuts as well as milk, meat, and
dried fruits. Twenty-five percent of the worlds crops are affected with
mycotoxins. On a worldwide scale, the aflatoxins are found in stored food
commodities and oil seeds. Some of the foods on which aflatoxin producing
fungi grow well include cereals (maize, sorghum, pearl millet, rice, wheat,
corn, oats, barley), oilseeds (peanut, soybean, sunflower, cotton), spices (chile
peppers, black pepper, coriander, turmeric, ginger), and tree nuts (almond,
pistachio, walnut, coconuts), sweet potatoes, potatoes, sesame, cacao beans,
almonds, etc., which on consumption pose health hazards to animals, including
Preface xv
aquaculture species of fish, and humans. Food commodities affected by
aflatoxins are also susceptible to other types of mycotoxins and multiple
mycotoxins can co-exist in the same commodity. Various cereals affected by
aflatoxins are also susceptible to contamination by fumonisins, trichothecenes
(especially deoxynivalenol), zearalenone, ochratoxin A and ergot alkaloids.
More than 5 billion people in developing countries worldwide are at risk
of chronic exposure to naturally occurring aflatoxins through contaminated
foods. Aflatoxin is a potent liver toxin causing hepatocarcinogenesis,
hepatocellular hyperplasia, hepatic necrosis, cirrhosis, biliary hyperplasia, and
acute liver damage in affected animals. Effects of aflatoxins in animals depend
on age, dose and length of exposure, species, breed and nutritional status of the
animal. Health effects occur in fish, companion animals, livestock, poultry and
humans because aflatoxins are potent hepatotoxins, immunosuppressants,
mutagens, carcinogens and teratogens. Aflatoxin B
1
has been shown to cause
significant morphological alterations along with reduced phagocytic potential
in chicken and turkey macrophages. Aflatoxin- B
1
exposure to chicken
embryos causes significant suppression in macrophage phagocytic potential in
chicks after hatch. Aflatoxin intercalates into DNA and alkylates the DNA
bases through its epoxide moiety resulting in liver cancer. Other effects
include mutagenic and teratogenic effects. Exposure of biological systems to
harmful levels of aflatoxin results in the formation of epoxide, which reacts
with proteins and DNA leading to DNA-adducts, thus causing liver cancer.
The primary target of aflatoxins is the hepatic system. Acute effects include
hemorrhagic necrosis of the liver and bile duct proliferation while chronic
effects include hepatocellular carcinoma (HCC). HCC is the sixth most
prevalent cancer worldwide with a higher incidence rate within developing
countries. Preliminary evidence suggests that there may be an interaction
between chronic aflatoxin exposure and malnutrition, immunosuppression,
impaired growth, and diseases such as malaria and HIV/AIDS. Outbreaks of
acute aflatoxin poisoning are a recurrent public health problem. The discussion
of this problem and its remedies must be held in the context of the associated
question of food insufficiency and more general economic challenges in
developing countries. Aflatoxin constitutes a serious health concern to the
entire food chain, necessitating a multidisciplinary approach to analysis,
action, and solution.
In: Aflatoxins ISBN: 978-1-63117-298-4
Editor: Adina G. Faulkner 2014 Nova Science Publishers, Inc.
Chapter 1
BIO-PREVALENCE, DETERMINATION
AND REDUCTION OF AFLATOXIN B
1
IN CEREALS
J elka Pleadin
1,
, Ksenija Markov
2
, J adranka Frece
2
,
Ana Vuli
1
and Nina Peri
1
1
Croatian Veterinary Institute,
Laboratory for Analytical Chemistry, Zagreb, Croatia
2
Faculty of Food Technology and Biotechnology,
Zagreb, Croatia
ABSTRACT
Moulds of Aspergillus genus are among the most important causes of
food and feed spoilage and can produce mycotoxins as toxic secondary
metabolites when under adverse conditions. Aflatoxins are a group of
mycotoxins that commonly contaminate maize and groundnuts, and are
categorized by the International Agency for Research on Cancer under
Class 1A human carcinogens. From the food safety standpoint, one of the
most important mycotoxins is aflatoxin B
1
(AFB
1
). Due to its potent
carcinogenic, teratogenic and mutagenic effects dependent on the level
and length of exposure, the presence of this contaminant in food and feed
should be kept as low as achievable. In order to investigate the
occurrence of AFB
1
, determine its concentrations and explore the
1,2
, Renata Galhardo Borguini
1
and Armando Venncio
2
1
EMBRAPA Food Technology, Rio de Janeiro, RJ, Brazil
2
IBB - Institute for Biotechnology and Bioengineering,
Center of Biological Engineering, Universidade do Minho,
Campus de Gualtar, Braga, Portugal
ABSTRACT
Brazil nut is an important non-timber forest product produced in
Amazon region. This nut is used as food with high value in the
international market, due to its high nutritional and flavor characteristic
and to their association with environmental conservation and alleviation
of poor people living from Amazonia. Annually, several hundred tons of
Brazil nuts are produced in Brazil. However, they are susceptible to
aflatoxins (AF) contamination. Because of the detection of unacceptable
level of AF in Brazil nuts consignments arriving in European Union
ports, in 2003, special conditions were imposed on Brazil nuts entering
the European Union, decreasing the acceptable levels of AF. In 2010, the
European Union revised AF regulation on nuts; these new limits are more
adequate when considering the complexity of Brazil nut chain and the
2
, Shelly Rana
2
,
Anand Sagar
2
and N. K. Dubey
3
1
G.B. Pant Institute for Himalayan Environment and Development
Himachal Unit, Mohal- Kullu, Himachal Pradesh, India
2
Mycology & Plant Pathology Laboratory, Department of Bio-Sciences,
Himachal Pradesh University, Shimla, India
3
Laboratory of Herbal Pesticide, Centre of Advanced Study in Botany,
Banaras Hindu University, Varanasi, India
ABSTRACT
This review deals with the aflatoxins especially with their food
sources, wide occurrence and toxicological effects on animals and
humans. Aflatoxins are highly oxygenated, heterocyclic,
difuranocoumarin compounds and are an important group of mycotoxins
produced by the fungi. There are almost 20 different types of aflatoxins
identified till now; among these AFB
1
is considered to be the most toxic.
Aflatoxins persist to some extent in food even after the inactivation of the
fungi by food processing methods, such as ultra-high temperature
Corresponding Author: Dr. Bhawana Srivastava, (Dr. D.S. Kothari postdoctoral fellow, UGC),
Mycology & Plant Pathology Laboratory, Department of Bio-Sciences, Himachal Pradesh
University, Shimla, India-171005, Tel: 91-9889206615, 91-177-2621692, e-mail:
bhawana.bhu@gmail.com.
Lipika Sharma, Bhawana Srivastava, Shelly Rana et al. 260
products, due to their significant chemical stability. Aflatoxins can affect
a wide range of commodities including cereals, oilseeds, spices, and tree
nuts as well as milk, meat, and dried fruits. Twenty five percent of the
worlds crops are affected with mycotoxins. On a worldwide scale, the
aflatoxins are found in stored food commodities and oil seeds. Some of
the foods on which aflatoxin producing fungi grow well include cereals
(maize, sorghum, pearl millet, rice, wheat, corn, oats, barley), oilseeds
(peanut, soybean, sunflower, cotton), spices (chile peppers, black pepper,
coriander, turmeric, ginger), and tree nuts (almond, pistachio, walnut,
coconuts), sweet potatoes, potatoes, sesame, cacao beans, almonds, etc.,
which on consumption pose health hazards to animals, including
aquaculture species of fish, and humans. Food commodities affected by
aflatoxins are also susceptible to other types of mycotoxins and multiple
mycotoxins can co-exist in the same commodity. Various cereals affected
by aflatoxins are also susceptible to contamination by fumonisins,
trichothecenes (especially deoxynivalenol), zearalenone, ochratoxin A
and ergot alkaloids.
More than 5 billion people in developing countries worldwide are at
risk of chronic exposure to naturally occurring aflatoxins through
contaminated foods. Aflatoxin is a potent liver toxin causing
hepatocarcinogenesis, hepatocellular hyperplasia, hepatic necrosis,
cirrhosis, biliary hyperplasia, and acute liver damage in affected animals.
Effects of aflatoxins in animals depend on age, dose and length of
exposure, species, breed and nutritional status of the animal. Health
effects occur in fish, companion animals, livestock, poultry and humans
because aflatoxins are potent hepatotoxins, immunosuppressants,
mutagens, carcinogens and teratogens. Aflatoxin B
1
has been shown to
cause significant morphological alterations along with reduced
phagocytic potential in chicken and turkey macrophages. Aflatoxin- B
1
exposure to chicken embryos causes significant suppression in
macrophage phagocytic potential in chicks after hatch. Aflatoxin
intercalates into DNA and alkylates the DNA bases through its epoxide
moiety resulting in liver cancer. Other effects include mutagenic and
teratogenic effects. Exposure of biological systems to harmful levels of
aflatoxin results in the formation of epoxide, which reacts with proteins
and DNA leading to DNA-adducts, thus causing liver cancer. The
primary target of aflatoxins is the hepatic system. Acute effects include
hemorrhagic necrosis of the liver and bile duct proliferation while chronic
effects include hepatocellular carcinoma (HCC). HCC is the sixth most
prevalent cancer worldwide with a higher incidence rate within
developing countries. Preliminary evidence suggests that there may be an
interaction between chronic aflatoxin exposure and malnutrition,
immunosuppression, impaired growth, and diseases such as malaria and
HIV/AIDS. Outbreaks of acute aflatoxin poisoning are a recurrent public
health problem. The discussion of this problem and its remedies must be
Aflatoxins As Serious Threats to Economy and Health 261
held in the context of the associated question of food insufficiency and
more general economic challenges in developing countries. Aflatoxin
constitutes a serious health concern to the entire food chain, necessitating
a multidisciplinary approach to analysis, action, and solution.
Keywords: Aflatoxons, Aspergillus sp., Hepatotoxins, Mycotoxins,
Occurrence, Toxicological Effects
INTRODUCTION
One of the greatest challenges of the world is to produce enough food for
the growing population. The situation is particularly critical in developing
countries, where the rate of net food production is slowing down in relation to
population growth. The world food situation is aggravated by the fact that in
spite of the use of all available means of plant protection, about one-third of
the yearly harvest of the world is destroyed by pests (Varma and Dubey,
1999). Considerable postharvest losses of food commodities are brought about
by infestations caused by different pests. International agencies that monitor
world food resources have acknowledged that one of the most feasible options
for meeting future food needs is reduction of postharvest losses (Kelman,
1984; Tripathi and Dubey, 2004). Fungi are significant destroyers of
foodstuffs during storage, rendering them unfit for human consumption by
retarding their nutritive value and sometimes by producing mycotoxins.
Approximately 2540% of cereals world-wide are contaminated with
mycotoxins produced by different storage fungi (Kumar et al., 2007). Tropical
countries, because of their temperature and congenial environment suffer
severe losses from pests due to conducive atmosphere. Generally, conditions
of these countries such as high temperatures and moisture, unseasoned rains
during harvest and flash floods lead to fungal proliferation and mycotoxins.
Aflatoxin belongs to a group of fungal toxins known as mycotoxins; these
are highly oxygenated, heterocyclic, difuranocoumarin compounds and are an
important group of mycotoxins produced by the fungi Aspergillus flavus, A.
parasiticus and A. nomius (Diaz et al., 2008).Other species of Aspergillus such
as A. bombycis, A. ochraceoroseusand A. pseudotamari mayalso produce
aflatoxins (Bennett & Klich, 2003; Klich et al., 2000; Mishra & Das, 2003;
Akbarsha et al., 2011). These species contaminate various agricultural
commodities either before harvest or at post-harvest stages under favorable
conditions of temperature and humidity. The discovery of aflatoxins dates
Lipika Sharma, Bhawana Srivastava, Shelly Rana et al. 262
back to the year 1961 following the severe outbreak of turkey X disease, in
the England, which resulted in the deaths of more than 100.000 turkeys and
other farm animals. Aflatoxins are toxic secondary metabolites produced by
Aspergillus fungus growing in susceptible agricultural commodities. They can
result in major economic losses and can negatively affect animal and human
health. The name aflatoxins, an acronym, has been formed from the following
combination : the first letter, A for the genus Aspergillus, the next set of
three letters, FLA, for the species flavus, and the noun TOXIN meaning
poison (Rustom,1997; Filazi & Sireli,2013).
Characteristics and Types
Once aflatoxin is produced, it is stable. Heat, cold and light do not affect
it. It is also colorless, odorless and tasteless, and because of the low
concentrations involved and the uneven distribution in grain bins, aflatoxins
are difficult to detect. Aflatoxins persist to some extent in food even after the
inactivation of the fungi by food processing methods, such as ultra-high
temperature products, due to their significant chemical stability (De Viries,
1997; Peraica, 1999). There are almost 20 different types of aflatoxins
identified till now, among these B1, B2, G1 andG2 are more prominent while
AFB1 is considered to be the most toxic (IARC,2002; Mushtaq et al. 2012).
There are four major natural aflatoxins (AFs), AFB1, AFB2, AFG1 and
AFG2. The hierarchy of toxicity of different aflatoxins is in the order
AFB1>AFG1>AFB2>AFG2. There are two additional metabolic products of
aflatoxins B1and B2, viz., M1 and M2. Aflatoxin M1 (AFM1) is a major
metabolite of aflatoxin B1 (AFB1), which is formed when animals ingest feed
contaminated with aflatoxin B1. The AFB1, once ingested by the animal, is
rapidly absorbed by the gastrointestinal tract and is transformed into the
metaboliteAFM1, which appears in the blood after 15 minutes and is then
secreted in the milk by the mammary gland (Van Egmond, 1989; Battacone, et
al. 2003). The amount of AFM1 which is found in milk depends on several
factors, such as animal breed, lactation period, mammary infections etc It
has, anyway, been demonstrated that up to 6% of the ingested AFB1 is
secreted into the milk as aflatoxin M1 (Van Egmond & Dragacci, 2001) and,
because AFM1is relatively resistant to heat treatments (Yousef & Marth,
1989; Galvano et al., 1996), it is almost entirely retained in pasteurized milk,
powdered milk, and infant formula. Moreover,only a limited decrease of
AFM1 content has been verified in UHT milk after long storage(Galvano et
Aflatoxins As Serious Threats to Economy and Health 263
al., 1996; Martins & Martins, 2000; Tekinsen & Eken, 2008). Aflatoxin B
1
(AFB
1
) is the most potent and potentially lethal metabolite and is a known
human carcinogen. The hepatotoxicity and carcinogenic effects of AFB1 have
been clearly demonstrated, thus it has long been classified as a group 1 human
carcinogen by the International Agency on Research on Cancer (IARC, 2002).
Initially, the IARC classified AFM1 as a possible carcinogen for humans
(group 2b) since toxicological data was limited (IARC, 1993). However,
genotoxicity and cancerogenity of AFM1 have been observed in vivo,
although lower than those of AFB1, and its cytotoxicity has been definitively
demonstrated (Caloni et al., 2006). As a result of these and other further
investigations, the IARC moved aflatoxin M1 from group 2B to group 1
human carcinogen (IARC, 2002, Anfossi et al., 2011).
Figure 1. Structure of some major aflatoxins.
Factors That Affect Aflatoxin Contamination
Factors that affect aflatoxin contamination include the climate of the
region, the genotype of the crop planted, soil type, minimum and maximum
daily temperatures, and daily net evaporation (Wilson and Payne 1994; Ono,
Lipika Sharma, Bhawana Srivastava, Shelly Rana et al. 264
Sugiura et al. 1999; Brown, Chen et al. 2001; Bankole and Mabekoje 2004;
Fandohan, Gnonlonfin et al. 2005). Aflatoxin contamination is also promoted
by stress or damage to the crop due to drought prior to harvest, insect activity,
poor timing of harvest, heavy rains at harvest and post-harvest, and inadequate
drying of the crop before storage (Hell, Cardwell et al. 2000; Ono, Sasaki et al.
2002; Hawkins, Windham et al. 2005; Turner, Sylla et al. 2005). Humidity,
temperature, and aeration during drying and storage are major factors behind
contamination.
Table 1. Chemical and physical properties of aflatoxins
Aflatoxin Molecular
formula
Molecular weight Melting point
(
0
C )
B
1
C
17
H
12
O
6
312 268-269
B
2
C
17
H
14
O
6
314 286-289
G
1
C
17
H
12
O
7
328 244-246
G
2
C
17
H
14
O
7
330 237-240
M
1
C
17
H
12
O
7
328 299
M
2
C
17
H
14
O
7
330 293
B
2A
C
17
H
14
O
7
330 240
G
2A
C
17
H
14
O
8
346 190
Food Sources and Occurrence
Well-known within the agricultural community, aflatoxins have been
studied for over forty years due to their widespread occurrence and their
significant impact on crops (Eaton and Groopman 1994; Wild and Turner
2002; Shephard 2003; Fung and Clark 2004; Williams, Phillips et al. 2004).
Aflatoxins are toxic secondary metabolites produced by Aspergillus fungi.
Aflatoxins can affect a wide range of commodities including cereals, oilseeds,
spices, and tree nuts as well as milk, meat, and dried fruit. Twenty five percent
of the worlds crops are affected with mycotoxins. Some of the foods on which
aflatoxin producing fungi grow well include cereals (maize, sorghum, pearl
millet, rice, wheat, corn ), oilseeds (peanut, soybean, sunflower, cotton), spices
(chile peppers, black pepper, coriander, turmeric, ginger), and tree nuts
(almond, pistachio, walnut, coconuts). Many of the above mentioned
ingredients are used in human food andin various livestock and poultry feed
rations and so these species are often contaminated with aflatoxin (Mushtaq et
Aflatoxins As Serious Threats to Economy and Health 265
al. 2012). The major sources of exposure are maize and groundnuts as these
are the foods that are most susceptible to contamination and consumed in the
greatest amounts. Aflatoxins are most prevalent in areas located between
latitudes 40N and 40S of the equator. On a worldwide scale, the aflatoxins
are found in stored food commodities and oil seeds such ascorn, peanuts,
cottonseed, rice, wheat, oats, barley, sorghum, millet, sweet potatoes, potatoes,
sesame, cacao beans, almonds, etc., which on consumption pose health
hazards to animals, including aquaculture species of fish, and humans (Abdel-
Wahab et al., 2008;Hussein & Brassel, 2001; Akbarsha et al., 2011). The
greatest risk for health impact lies within developing countries located in
tropical regions, which rely on these commodities as their staple food source.
Food insufficiency and lack of diversity substantially contribute to the
susceptibility of individuals and communities to aflatoxins.
Various approaches exist for the determination of aflatoxin in food and
feed commodities. Generally, all analytical methods follow the basic protocol
of extraction, clean-up, separation, detection, identification and quantification.
However, the most widely used techniques are those which include a
chromatographic step to separate the mycotoxin of interest like minicolumn
chromatography, thin layer chromatography, high performance liquid
chromatography and gas liquid chromatography.
Figure 2. Presentation showing economic loss because of aflatoxin occurrence.
Lipika Sharma, Bhawana Srivastava, Shelly Rana et al. 266
Although immunoassay-based quantitative methods are fast and
promising, for mycotoxin research they have the possibility of producing mis-
leading results because of cross-reaction and interference in the complex
matrixes (Nilu & Boyaciog, 2002; Hu, 2006; Mushtaq et al. 2012).
Toxicological Effects
The health issues related to aflatoxins are equally complex and demand
more research. The ingested aflatoxin undergoes various possible pathways
depending on different parameters like dose quantity, type of species, age,
diet, and immune system of host. Aflatoxin is a potent liver toxin causing
hepato-carcinogenesis, hepatocellular hyperplasia, hepatic necrosis, cirrhosis,
biliary hyperplasia, and acute liver damage in affected animals. Other effects
include mutagenic and teratogenic effects. Large doses of aflatoxin are lethal
and chronic exposure to low levels of aflatoxin can result in cancer and
immunosuppression (Sharma, 1993; Yarru, 2008). Exposure of biological
systems to harmful levels of aflatoxin results in the formation of epoxide,
which reacts with proteins and DNA leading to DNA-adducts, thus causing
liver cancer (Turner et al., 2009; Groopman et al., 2008). Infants are at much
higher risks of health problems compared to adults (Sergent et al., 2008).
Aflatoxins, in general, and AFB1 in particular, can induce DNA damage, gene
mutation, sister-chromatid exchanges and other chromosomal anomalies,
which account for their genotoxic, teratogenic and carcinogenic properties
(Batt et al., 1980; International Agency for Research on Cancer (IARC, 1993;
Ray-Chaudhuri et al., 1980). AFB1 can form adducts with DNA, RNA and
protein, which form the major basis of the health risks (Sun et al., 2001;
Williams et al., 2004). The maximum legal limit allowed for AFB1 in infant
food in the European Union is 0.1 g kg
1
(European Commission, 2006). In
developing countries, the majority of the people survive largely on cereal
based diets. Consequently, nutritional deficiencies are very prevalent in
populations consuming high levels of cereals, particularly in children (Bankole
& Adebenjo, 2003). Moreover, poor diet and multiple infectious hazards are
associated with malnutrition and growth faltering in infancy and childhood
(IARC, 2002). More than 5 billion people in developing countries worldwide a
great risk of chronic exposure to naturally occurring aflatoxins through
contaminated food (Shephard, 2003; Williams et al., 2004) and more so in the
tropical regions, where the climatic conditions favour luxurious growth of
Aspergillus spp, and people rely on commodities such as cereals, oilseeds,
Aflatoxins As Serious Threats to Economy and Health 267
spices, tree nuts, milk, meat and dried fruits that are potentially contaminated
by aflatoxins (Strosnider et al., 2006). In July 2005, the United States Centers
for Disease Control and Prevention (US CDC) and the World Health
Organization (WHO) hosted a workshop to create an integrated plan intended
to generate culturally appropriate, long-term, public health strategies to reduce
aflatoxin exposure in developing countries. Participants included 40
internationally recognized scientists from diverse backgrounds (i.e. public
health, agriculture, animal health, trade and social science) and key public
health officials and stakeholders from countries heavily affected by aflatoxins.
Aflatoxins affect many species including humans, dogs, feeder pigs, dairy
cattle, and chickens.
Effects of Aflatoxins on Animal Health
The effects of aflatoxins on animal health have been observed in many
species for over forty years (Patten 1981; Miller and Wilson 1994) beginning
with the documentation of Turkey X disease in 1960. The primary target of
aflatoxins is the hepatic system. Acute effects include hemorrhagic necrosis of
the liver and bile duct proliferation while chronic effects include
hepatocellular carcinoma (HCC). In animals, suppression of immunity, growth
retardation, and increased susceptibility to infectious disease due to aflatoxin
exposure is well-documented (Patten 1981; Miller and Wilson 1994). Trout,
one of the early models for aflatoxicosis is very sensitive to aflatoxin and
develop clinical signs such as hepatoma. Swine at weaning and marketing
stages are resistant to dietary levels of aflatoxins up to300 ppb. Clinical signs
associated with aflatoxicosis in dairy cattle include reduced feed intake, milk
production, weight gain and liver damage. Aflatoxin M1, an aflatoxin
metabolite found in milk, was also found in milk products such as yogurt
(Martins M.L e tal., 2004; Yarru, 2008). Symptoms of aflatoxicosis include
feed refusal, decreased feed efficiency, and stunted growth, decreased milk
production and impaired reproductive efficiency (Diekman& Green, 1992;
Oguz&Kurtoglu, 2000; Pier, 1992; Raju & Devegowda, 2000). Numerous
studies have shown that feed intake is reduced in broiler chicks fed aflatoxin
(Osborn et al., 1992; Ledoux et al., 1998). Reduced feed intake results in
decreased average daily gain (Ledoux et al., 1998). One important thing to be
determined is the effects of aflatoxin on nutrient digestibility and
bioavailability. This can be done by measuring the activity and levels of
various digestive enzymes and by evaluating serum chemistry of affected
Lipika Sharma, Bhawana Srivastava, Shelly Rana et al. 268
animals. Balachandran and Ramakrishnan (1987) studied the influence of
dietary aflatoxin on serum enzyme levels in broiler chicken. They measured
SGPT, SGOT, serum amylase and lipase levels in Cobb broiler chickens fed
3ppm aflatoxin.
Table 2. FDA action levels for aflatoxins in human and animal foods
Commodities . Total aflatoxin
action level (ppb)
Human food 20
Milk 0.5
Beef cattle 300
Swine over 100 lbs 200
Breeding beef cattle, swine, or mature poultry 100
Corn for immature animals and dairy cattle 20
Corn for breeding beef cattle, swine and mature poultry 100
Corn for finishing swine 200
Corn for finishing beef cattle 300
Cottonseed meal (as feed ingredient) 300
All feedstuff other than corn 20
Source: Wu, et al. 2011.
They observed an increase in serum lipase and SGOT levels, and a
decrease in serum amylase levels all of which resulted in alteration in nutrient
digestion, absorption and metabolism. Osborne and Hamilton, (1981) observed
decreased serum lipase, amylase, trypsin, lipase, RNase, and DNase activities
in chickens fed aflatoxin. They did not measure serum calcium and
phosphorus levels which play a role in rubbery leg syndrome, one of the
symptoms associated with aflatoxicosis. Health effects occur in fish,
companion animals, livestock, poultry and humans because aflatoxins are
potent hepatotoxins, immunosuppressants, mutagens, carcinogens and
teratogens. Public health concerns center on both primary poisoning from
aflatoxins in commodities, food and feedstuffs, and relay poisoning from
aflatoxins in milk (Coppock& Christian, 2007). The ability of the immune
system to combat infection and disease is another key component of animal
health. Aflatoxin B
1
has been shown to cause significant morphological
alterations along with reduced phagocytic potential in chicken (Neldon-ortiz
and Qureshi, 1991a) and turkey (Neldon-ortiz and Qureshi, 1991b)
macrophages. Aflatoxin-B1 exposure to chicken embryos causes significant
Aflatoxins As Serious Threats to Economy and Health 269
suppression in macrophage phagocytic potential in chicks after hatch (Neldon-
ortiz and Qureshi, 1991c; Yarru, 2008).
Effects of Aflatoxins on Human Health
The effects of aflatoxins on humans, as with animals, are dependent upon
dosage and duration of exposure. Acute exposure can result in aflatoxicosis,
which manifests as severe, acute hepatotoxicity with a case fatality rate of
approximately 25% (Cullen and Newberne 1994). Early symptoms of
hepatotoxicity from aflatoxicosis can manifest as anorexia, malaise, and low-
grade fever.
Figure 3. A picture summarizing main characteristics of aflatoxins.
Acute high level exposure can progress to potentially lethal hepatitis with
vomiting, abdominal pain, jaundice, fulminant hepatic failure, and death.
Outbreaks of acute aflatoxicosis are a recurring public health problem
throughout the world (Krishnamachari, Bhat et al. 1975; Ngindu, Johnson et
al. 1982; Lye, Ghazali et al. 1995; CDC 2004).Hepatocellular carcinoma
(HCC) as a result of chronic exposure has been well documented, generally in
association with hepatitis B virus or other risk factors (Qian, Ross et al. 1994;
Lipika Sharma, Bhawana Srivastava, Shelly Rana et al. 270
Wang, Hatch et al. 1996; Chen, Chen et al. 2001; Henry, Bosch et al. 2002;
Omer, Kuijsten et al. 2004). The International Agency for Research on Cancer
(IARC) first recognized aflatoxins as carcinogenic in 1976 and has
subsequently reaffirmed naturally occurring mixtures of aflatoxins and
aflatoxin B1 as Group 1 carcinogens (carcinogenic to humans) (IARC 2002).
Additional effects of chronic exposure have not been widely studied but are
thought to include immunologic suppression, impaired growth, and nutritional
interference (Patten 1981; Cullen and Newberne 1994; Fung and Clark 2004;
Williams, Phillips et al. 1994).
Health Impact and Burden of Disease
HCC is the sixth most prevalent cancer worldwide with a higher incidence
rate within developing countries (Parkin, Bray et al. 2005), however, the
burden of HCC attributable to aflatoxins when accounting for other co-
morbidities, such as hepatitis B (HBV), is not known. Several studies in China
have indicated combined exposure to HBV and aflatoxins is associated with a
much higher risk of HCC (Qian, Ross et al. 1994; Wang, Hatch et al. 1996).
This interaction has not been studied in other high risk areas such as sub-
Saharan Africa and the molecular mechanism of the interaction between HBV
and aflatoxins is not known (Turner, Sylla et al. 2002; Wild and Turner 2002).
Quantifying the proportion of HCC attributable to aflatoxin exposure, to HBV,
and to the interaction of aflatoxin exposure and HBV will help identify the
best public health strategy to reduce HCC, including the benefits and limits of
widespread HBV vaccination. Additional health effects associated with
chronic aflatoxin exposure have not been well studied. Without knowing the
relationship between chronic exposure and health, the true human health
impact and the resulting burden of disease in developing countries are not
known. Preliminary evidence suggests that there may be an interaction
between chronic aflatoxin exposure and malnutrition, immunosuppression,
impaired growth, and diseases such as malaria and HIV/AIDS. Experimental
animal evidence suggests that chronic exposure to aflatoxins may lead to
impaired immunity, reduced uptake of nutrients from the diet, and growth
retardation (Hall and Wild 1994; Miller and Wilson 1994). Several studies of
children in Benin and Togo have shown an association between aflatoxin
albumin adduct levels and impaired growth (Gong, Cardwell et al. 2002;
Gong, Egal et al. 2003; Gong, Hounsa et al. 2004). In a recent study in Ghana,
higher levels of aflatoxin B1-albumin adducts in plasma were associated with
Aflatoxins As Serious Threats to Economy and Health 271
lower percentages of certain leukocyte immune phenotypes (Jiang, Jolly et al.
2005). A study in Gambian children found an association between serum
aflatoxin-albumin levels and reduced salivatory secretory IgA levels (Turner,
Moore et al. 2003). While the effects on immunity suggest the possible
influence of aflatoxins on susceptibility to infectious disease, further
investigation is needed.
Aflatoxin associated health effects pervade the developing world despite
the fact that these effects could be mitigated or prevented with the current state
of agricultural knowledge and public health practice. The discussion of this
problem and its remedies must be held in the context of the associated
question of food insufficiency and more general economic challenges in
developing countries. Outbreaks of acute aflatoxin poisoning are a recurrent
public health problem. In 2004, one of the largest, most severe aflatoxicosis
outbreaks occurred in Kenya followed by another outbreak in 2005 (CDC
2004). Given that diseases in the developing world often go unreported, the
Kenya outbreaks are likely to be an underestimation of the problem;
furthermore, the burden of disease attributable to chronic aflatoxin exposure
(e.g. hepatocellular carcinoma, impaired growth, immune suppression)
remains undefined. These outbreaks emphasize the need to quantify and
control aflatoxin exposure in developing countries and highlight the potential
role of public health.
A broad range of signs and symptoms can be used to diagnose
aflatoxicosis based on the level of exposure. The signs and symptoms of this
condition include vomiting, abdominal pain and hemorrhaging, pulmonary
edema, acute liver damage, loss of digestive tract function, convulsions,
cerebral edema, and coma. Hepatitis B vaccinations, education through
awareness campaigns, and chemoprevention measures such as competitive
displacement, plant extract application, and methyl eugenol spray have proven
to be effective interventions in controlling and preventing the adverse health
effects of aflatoxin exposure (Right Diagnosis, 2011). Aflatoxin constitutes a
serious health concern to the entire food chain, necessitating a
multidisciplinary approach to analysis, action, and solution. To maximize
resources, a targeted monitoring and surveillance system for high-risk areas
and their populations should collect and analyze appropriate specimens
(usually food, urine, and serum) (Strosnider, 2006). Aflatoxicosis is a disease
caused by aflatoxin poisoning. The disease can be acute, meaning it is caused
by the short-term exposure to high levels of aflatoxin, or chronic, meaning that
it has been caused by long-term exposure to low to moderate levels of
Lipika Sharma, Bhawana Srivastava, Shelly Rana et al. 272
aflatoxin. Symptoms differ between the acute and chronic forms of the disease
and have been outlined in this section.
Acute Aflatoxicosis
Acute aflatoxicosis, associated with extremely high doses of aflatoxin, is
characterized by hemorrhaging, acute liver damage, edema, and high mortality
rates in humans. Acute aflatoxicosis is associated with sporadic outbreaks of
the consumption of highly contaminated foods. Early symptoms of acute high
level exposure to aflatoxin include diminished appetite, malaise, and low
fever; later symptoms, which include vomiting, abdominal pain, and hepatitis,
can signal potentially fatal liver failure (Barret, 2005). Acute aflatoxicosis in
animals was first documented in 1960, after more than 100,000 turkeys died
following an outbreak in the United Kingdom (Wu et al., 2011.)
Chronic Aflatoxicosis
Chronic aflatoxicosis is associated with long-term exposure to low to
moderate levels of aflatoxin in the food supply. Chronic low-level exposure to
aflatoxin, particularly aflatoxin B1, is associated with an increased risk of
developing hepatocellular carcinoma, or liver cancer, as well as impaired
immune function and malnutrition and stunted growth in children. Aflatoxin
B1 is the most potent liver carcinogen and is found in greater concentrations
than any other naturally occurring aflatoxin (Wu et al., 2011; Bhat, &
Vasanthi, 2003). According to the World Health Organization (WHO),
hepatocellular carcinoma is the third leading cause of cancer deaths globally
(WHO., 2008). Approximately 83 percent of cancer fatalities in East Asia and
Sub-Saharan Africa are due to liver cancer (Parkin et al., 2002; Strosnider et
al., 2006; Kirk et al., 2006). Hepatocellular carcinoma, as a result of chronic
aflatoxin exposure, presents most often in persons with a chronic hepatitis B
virus and/or chronic hepatitis C virus infections (Groopman & Kensler, 2005;
Wu & Khlangwiset, 2010; Liu & Wu, 2010). This indicates that exposure to
aflatoxin and hepatitis binfection, key risk factors for liver cancer, are
particularly prevalent in developing nations in which people subsist largely on
grains (Liu & Wu, 2010). Chronic aflatoxicosis also increases the risk of
developing impaired immune function and malnutrition, a concern already
prevalent in populations consuming high levels of cereals (Wu et al., 2011;
Aflatoxins As Serious Threats to Economy and Health 273
Bhat & Vasanthi, 2003; Bankole & Adebanjp, 2003). Cancer risk assessments
and acute toxicity studies acrossspecies show that adult humans are relatively
tolerant of aflatoxin; however, data reviewed in earlier sections indicate that
there is evidence that aflatoxin exposure affects early development, as well as
some aspects of human immunity and nutritional processes (Williams et al.,
2004). Maize (Zeamayis L.) and peanuts (Arachishypogaea L.) form the staple
food of many African and Asian diets. As these two crops are highly
susceptible to aflatoxin infection, the incidence of aflatoxin exposure is closely
related to the subsistence diet of populations in developing countries (Liu &
Wu, 2010). From 2001 to2003, developing countries produced 46 percent of
the global maize crop (Wu et al., 2011). Poor harvesting and storage practices
and weak regulations of mycotoxin contamination in developing countries
exacerbate rates of aflatoxin exposure (Wild & Gong, 2010).
Links to HIV and TB
It has been suggested that the immune suppression and nutritional effects
of chronic aflatoxin exposure may be linked to the high prevalence of HIV.
This possible link, however, is not conclusive, as research targeting the cancer-
causing effects of aflatoxin has generally overshadowed research focusing on
nutrition and immunity (Shekhar et al., 2009). Aflatoxin exposure has been
shown to cause immune suppression, particularly in cell-mediated responses
(Safarac et al., 2010).
The correlation between aflatoxin-albumin levels and CD4 counts in HIV
positive individuals has recently been studied. CD4 interacts with cells that act
as the gateway for HIV infection. CD4 proteins that have been weakened by
aflatoxin exposure may correlate positively with HIV infection (Nyandieka et
al., 2009). In addition, for the first time, new research has linked high aflatoxin
levels with an increased risk of developing tuberculosis (TB) in HIV positive
individuals. TB transmission associated with aflatoxin exposure raises a new
health concern among HIV positive individuals, in addition to concerns related
to increased susceptibility to liver disease (Allameh et al., 2005). Persons who
are exposed to aflatoxin and are HIV positive have decreased plasma vitamin
A and vitamin E in the blood, although there was no interaction detected
between aflatoxin and HIV infection (Safamehr, 2008). Nevertheless, other
mechanisms have been proposed to explain the link between HIV and
aflatoxin exposure. Williams et al. hypothesized that HIV infection is likely to
increase aflatoxin exposure by two possible routes: (1) HIV infection
Lipika Sharma, Bhawana Srivastava, Shelly Rana et al. 274
decreases the levels of antioxidant nutrients that promote the detoxification of
aflatoxin, or (2) the high degree of co-infection of HIV-infected people with
hepatitis B also increases the biological exposure to aflatoxin. Although no
specific studies on humans have yet been conducted, the evidence suggests a
decrease in animal immune systems as a result of aflatoxin exposure
(Dixon et al., 2008)
Co-Existence and Interactions of Multiple Mycotoxins
Food commodities affected by aflatoxins are also susceptible to other
types of mycotoxins and multiple mycotoxins can co-exist in the same
commodity (Bankole and Mabekoje 2004; Fung and Clark 2004; Speijers and
Speijers 2004).
Various cereals affected by aflatoxins are also susceptible to
contamination by fumonisins, trichothecenes (especially deoxynivalenol),
zearalenone, ochratoxin A and ergot alkaloids. Maize can be contaminated
with aflatoxins, fumonisin, trichothecenes, zearalenone and, rarely,
ochratoxin-A, while wheat can be contaminated with aflatoxins,
trichothecenes, ochratoxin-A, ergot alkaloids and zearalenone. Therefore
individuals may be exposed to various combinations of mycotoxins (CAST
2003). The health effects associated with exposure to multiple mycotoxins are
not well documented. Related mycotoxins are thought to have an additive
effect while unrelated mycotoxins may have a synergistic effect (Speijers and
Speijers 2004). A better understanding of exposure to multiple mycotoxins and
the health effects associated with the interactions of multiple mycotoxins
would clarify the true health impact of mycotoxins.
Future Prospective
As it has been mentioned before, most aflatoxicosis results from eating
contaminated foods. Unfortunately, except for supportive therapy (e.g., diet
and hydration) there are almost no treatments for aflatoxin exposure. In Figure
4, we reproduce an overview for preventing acute aflatoxicosis in developing
countries (Strosnider et. al., 2006). Methods for controlling aflatoxin exposure
are largely prophylactic. In a primary prevention trial, the goal is to reduce
exposure to aflatoxins in the diet. A range of interventions includes planting
pest-resistant varieties of staple crops, attempting to lower mold growth in
Aflatoxins As Serious Threats to Economy and Health 275
harvested crops, improving storage methods following harvest, and using
trapping agents that block the uptake of unavoidably ingested aflatoxins. In
secondary prevention trials, one goal is to modulate the metabolism of
ingested aflatoxin to enhance detoxification processes, thereby reducing
internal dose and subsequent risk (Groopman, 2008,).
Figure 4. Overview of preparedness, surveillance and response activities for preventing
acute aflatoxicosis (Strosnider et. al., 2006).
Further, more studies and researches are needed in order to develop
appropriate technology for treatment of aflatoxin exposure and to minimize
their resulting health effects. Aflatoxins are not only a big problem at crop
production level, but also it has become a global health issue because of the
consequences that the consumption of this toxin generates in animals and
human beings. Diverse worldwide established groups have the challenge of
Lipika Sharma, Bhawana Srivastava, Shelly Rana et al. 276
identifying public health strategies, which complement the agricultural ones in
order to reduce aflatoxin exposure, especially in developing countries.
Although there have been documented some researches about how to prevent
and control aflatoxicosis, but a little is known about aflatoxin exposure and the
resulting health effects. Efforts to reduce aflatoxin exposure require the
commitment of sufficient resources and the collaboration between the
agriculture and public health communities as well as local, regional, national,
and international governments.
Because of the recent investigations conducted, it is important to take
actions to prevent damage and diseases; thats why, at first, governments
supported by scientific research groups should report publicly the risks that
aflatoxins consumption means by quantifying the human health impacts and
the burden of disease due to the toxin exposure; then, they should compile
inventory and worldwide statistics in order to evaluate the efficacy of the
current intervention strategies. It is also important to increase disease
surveillance, food monitoring, laboratory detection of mycotoxins and public
health response capacity of affected regions. Public health services should
offer immediate attention to aflatoxicosis diagnoses and opportunistic diseases
caused by them in order to reduce mortality rates in humans and animals.
Finally, it is important to develop response protocols to be used in an event of
an outbreak of acute aflatoxicosis, which could become in an epidemic stage.
ACKNOWLEDGMENTS
The authors are thankful to the University Grants Commission, New Delhi
for providing financial assistance in the form of Dr. D.S. Kothari postdoctoral
fellowship and to Food and Public Health Branch of the Food and
Environmental Hygiene Department of HKSAR Government for their report.
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INDEX
A
access, 159, 219, 242, 251
accounting, 209, 239, 270
acetonitrile, 16
acetylcholinesterase, 200
acid, 11, 12, 16, 23, 25, 28, 50, 51, 54, 56,
57, 59, 85, 133, 143, 160, 185, 186, 190,
195, 236, 245, 283
activity level, 178
acute aflatoxin poisoning, xv, 260, 271
adaptation, 181
additives, 83, 253
adenine, 151
adenovirus, 155
adjustment, 115
adolescents, 278
adsorption, 11, 27
adults, 203, 204, 266
adverse conditions, vii, 1
adverse effects, ix, 6, 64, 210
advisory body, 205
aetiology, 152
aflatoxicosis, xiii, 8, 26, 30, 77, 79, 88, 104,
105, 192, 196, 198, 200, 223, 247, 267,
268, 269, 271, 272, 274, 275, 276, 281,
282, 283, 285
Africa, 45, 71, 80, 88, 122, 198, 201, 227,
272, 278, 280, 284, 285, 286
agar, 23, 57, 165, 171
age, xv, 5, 80, 85, 128, 129, 135, 138, 141,
142, 147, 155, 194, 202, 203, 204, 217,
237, 260, 266
agencies, 194, 209, 215, 219, 261
agribusiness, xi, 108, 113
agricultural market, 215
agriculture, ix, 28, 30, 32, 64, 222, 239, 267,
276
AIDS, 100
albumin, 80, 81, 94, 98, 99, 101, 103, 105,
136, 137, 151, 201, 227, 270, 273, 278,
280
alkaloids, xv, 260, 274
allele, 149
almonds, xiv, 5, 69, 70, 76, 78, 84, 112,
113, 121, 207, 208, 212, 220, 229, 260,
265
alveolar macrophage, 96, 103
amines, 29, 58, 85, 226, 254, 280
amino, 143, 146, 147, 181, 184
amino acid(s), 143, 146, 147
ammonia, 12, 200, 277, 283
amylase, 268
anatomy, 189
animal disease(s), 8, 210
animal feeds, xiv, 12, 217, 222, 234, 235,
239, 247, 278
animal welfare, 214
annealing, 132
anorexia, 6, 79, 269
ANOVA, 18
Index 288
antibiotic, 249
antibody, 10, 99, 100, 131, 201
antigen, 104, 129, 206, 278
antioxidant, 249, 257, 274, 281
apoptosis, 51, 151, 197, 200
apoptotic pathways, 96
appetite, 6, 272
appropriate technology, 275
aquaculture, xv, 260, 265
aqueous solutions, 14
ARC, 254
Argentina, vi, 42, 57, 78, 157, 159, 160,
161, 162, 163, 164, 166, 181, 183, 184,
185, 186, 187, 188, 189, 221
Argentinean peanut, xi, 157, 159, 166, 184
arthropods, 166, 185
ascites, 79
Asia, viii, 35, 41, 71, 198, 201
Asian countries, 75
aspergillosis, 52
Aspergillus terreus, 57, 60
assessment, 32, 83, 89, 109, 113, 118, 193,
202, 204, 205, 208, 209, 227, 228, 237,
238, 252, 253, 257, 284
atmosphere, 45, 261
attachment, 40
attribution, 211
authority(s), xiii, 9, 112, 114, 116, 192, 209,
211, 214, 215, 219, 230
autopsy, 79
avoidance, 4
awareness, 45, 271
B
B1 (AFB1), vii, ix, xi, 1, 3, 64, 92, 110,
126, 127, 159, 206, 235, 262
Bacillus subtilis, 11
bacteria, viii, 2, 4, 11, 23, 24, 25, 27, 28, 29,
30, 32, 50, 52, 53, 59, 240
bacterial cells, 53
bacterial strains, 23, 53
Bahrain, 78, 220
ban, 212
Bangladesh, 42
barriers, 110
base, 30, 40, 116, 143, 146, 197, 212
base pair, 197
BCG immunotherapy, 156
BD, 150
beef, 75, 78, 217, 268
benefits, 120, 270
benign, 197
beverages, 203
BI, 155
bias, 148
bile duct, xv, 260, 267
bioavailability, 12, 267
biochemical processes, 80
biochemistry, 277, 283
biodiversity, 162
biological activity(s), 19, 24, 182
biological consequences, 104, 283
biological control, 31, 53
biological samples, 29
biological systems, xv, 260, 266
biomarkers, xiii, 80, 82, 85, 86, 88, 102,
136, 143, 144, 145, 192, 222, 223
biomonitoring, 82
biosynthesis, 37, 45, 46, 47, 48, 49, 50, 54,
55, 56, 57, 59, 61, 62, 66, 86, 102, 186,
195, 198, 236, 243, 280
biotic, 36
birds, 195, 199, 200
birth weight, 198, 224
bladder cancer, 145, 146, 153
bleaching, 245
bleeding, 79
blood, 80, 97, 103, 104, 136, 139, 151, 196,
225, 262, 273
body fluid, 80
body weight, 195, 206
Bolivia, 108, 110, 114, 115, 121
Bosnia, 219, 221
Botswana, 42
brain, 200, 226
brain chemistry, 200
Brazil, v, x, 42, 58, 59, 68, 69, 76, 78, 82,
84, 107, 108, 109, 110, 111, 112, 113,
114, 115, 116, 118, 119, 120, 121, 122,
Index 289
123, 163, 181, 182, 184, 202, 203, 213,
219, 220, 228, 282
Brazil nuts, x, 68, 69, 76, 78, 82, 84, 107,
108, 109, 110, 111, 112, 113, 114, 115,
118, 119, 120, 121, 122, 123, 213, 220
breakfast cereals, xiv, 202, 234, 236, 249,
251, 252, 257
breast cancer, 143, 152, 153, 154
breast milk, 37, 57, 81, 225
breeding, 78, 217, 268
Britain, 92
buffalo, 73, 86, 89
Burkina Faso, 185
businesses, 67
by-products, 11, 119
C
Ca
2+
, 226
cacao, xiv, 260, 265
calcium, 12, 32, 268, 281
calibration, 15, 17
Cameroon, 38, 53
campaigns, 271
cancer, xv, 77, 79, 85, 88, 94, 111, 113, 130,
143, 146, 147, 151, 153, 154, 156, 197,
208, 223, 260, 266, 270, 272, 273, 282
cancer death, 272
CAP, 210
capillary, 16
carbohydrate(s), 184, 196, 197
carbon, 45, 47, 48
carbon dioxide, 45
carcinogen, ix, 3, 9, 29, 64, 79, 127, 148,
235, 263, 272
carcinogenesis, 28, 105, 127, 195, 266, 279
carcinogenicity, 31, 127, 193, 194, 198,
205, 208
carcinoma, 126, 155, 156, 195, 197, 269,
272
cardiovascular system, 250
carotenoids, 151, 249, 250
case study, 32, 144
catalysis, 225
cattle, 4, 6, 8, 9, 25, 32, 38, 75, 76, 78, 79,
217, 267, 268
CCA, 131
CD8+, 98
CDC, 216, 267, 269, 271, 278
cell cycle, 96, 197
cell death, 197, 226
cell killing, 12
cell line, 96, 153
cell surface, 96, 102
cellular immunity, 98
central nervous system, 95
cerebral edema, 79, 271
certificate, 111, 112
certification, 111, 112, 114, 118, 119, 219,
238
CFR, 26
challenges, xv, 261, 271
cheese, 24, 76, 84, 235, 239, 240, 242, 254,
258, 284
chemical(s), ix, xiv, 2, 10, 11, 12, 14, 29,
53, 64, 85, 87, 89, 155, 159, 217, 226,
235, 260, 262, 280
chemical stability, xiv, 260, 262
chemokines, 95
chemoprevention, 271
chemotaxis, 98, 105
Chicago, 135
chicken, xv, 260, 268, 281, 282
chicken embryos, xv, 260, 268
childhood, 155, 198, 266
children, xiii, 33, 69, 71, 76, 77, 79, 81, 85,
88, 100, 105, 192, 193, 194, 196, 198,
201, 202, 203, 204, 207, 214, 221, 224,
227, 239, 242, 251, 257, 266, 270, 272,
279, 285
China, 42, 71, 75, 84, 95, 125, 126, 127,
131, 150, 152, 154, 155, 185, 203, 219,
221, 228, 270, 283
chloroform, 130
cholesterol, 51
chromatid, 266, 277
chromatographic technique, 87
chromatography, 10, 29, 37, 54, 234, 238,
265
Index 290
chromosome, 45, 143, 145, 146, 147, 277
chromosome map, 45
chronic diseases, 198
chronic fatigue syndrome, xiii, 192, 193
cirrhosis, xv, 129, 226, 260, 266
City, 91, 125, 184, 224
cleaning, 108, 245
cleanup, 9
climate(s), viii, xiii, xiv, 2, 6, 8, 18, 36, 39,
43, 44, 45, 56, 59, 64, 66, 81, 82, 192,
234, 239, 240, 246, 247, 255, 256, 263
climate change, xiii, xiv, 44, 45, 192, 234,
256
climatic factors, 7
cloning, 62
clusters, 46, 48, 49, 60
cocoa, 81, 203
coding, 112, 143, 146, 152
codon, 131, 138, 139, 143, 144, 147, 148,
149, 152, 154, 156, 197, 222
coffee, 256
cognitive development, 198
cognitive function, 200
collaboration, 219, 276
colleges, 48
colonisation, 40, 41, 49
colonization, 166, 172, 187, 189, 242
color, 11, 109
colorectal cancer, 153, 154, 156
coma, 79, 271
commerce, 215
commercial, 8, 12, 25, 30, 73, 159, 207,
239, 240, 244, 246, 247, 255, 256
commodity, xv, 108, 113, 119, 202, 204,
208, 250, 251, 260, 274
communication, 50, 211
community(s), xii, 44, 158, 163, 172, 185,
264, 265, 276, 285
compatibility, 188
competition, 11, 66, 174, 245, 249
compilation, vii
complement, 82, 200, 276
complexity, xi, 107
compliance, 119, 194, 209, 215, 216, 218,
219, 230
composition, 11, 180, 181, 188, 235
compounds, viii, ix, xiii, xiv, 2, 3, 11, 12,
26, 29, 35, 37, 63, 92, 181, 184, 192,
205, 235, 245, 259, 261
concordance, 17
conditioning, xii, 158, 171, 173
confinement, 38
conflict, 120
conflict of interest, 120
conformity, 110, 118
confounders, 129, 135
congress, 218, 231
consensus, 46, 67
consent, 129
conservation, x, 107, 108, 110
constituents, 29, 58, 85, 245, 254, 255, 280
consumers, xi, 8, 108, 110, 113, 119, 194,
203, 204, 207, 208, 209, 210, 211, 215,
239
consumption patterns, 207
containers, 239
contaminant, vii, viii, 1, 8, 35, 41, 127, 168,
205, 212, 216
contaminated food, ix, xiii, xv, 5, 11, 63, 92,
113, 192, 194, 208, 260, 266, 272, 274
control group, 249
control measures, 237
controversial, 199
conversion rate, 6
cooking, 159
cooperation, 194
coordination, 54, 58, 200
copper, 12
correlation, 93, 101, 138, 147, 174, 178,
179, 183, 198, 201, 245, 273
cost, 9, 10, 11, 45, 70, 238, 286
Costa Rica, 33, 59
cotton, viii, xiv, 5, 35, 39, 40, 56, 58, 185,
251, 260, 264
coumarins, 127, 245
covalent bond, 93
covering, 8
CPT, 195
cracks, 41
crises, 247
Index 291
Croatia, 1, 13, 18, 19, 22, 23
crop(s), viii, xiii, xiv, 3, 4, 6, 7, 31, 35, 36,
37, 38, 39, 40, 41, 44, 49, 52, 53, 59, 62,
66, 67, 73, 116, 159, 163, 164, 166, 189,
192, 194, 236, 252, 255, 256, 260, 263,
264, 273, 274, 275, 280, 282
crop production, 275
crop residue, 67
cross sectional study, 198, 224, 279
CT, 133, 137, 138, 140, 141, 144, 149, 155
cues, 47
cultivars, 181, 190, 257
cultivation, vii, xiv, 2, 4, 22, 67, 163, 164,
202, 203, 234, 236, 250
cultural conditions, 48
cultural practices, 53, 164
culture, 45, 57, 165, 176, 225, 244
culture conditions, 165
culture media, 244
culture medium, 176
current limit, 119
CV, 14
cycles, 131
cytochrome, xi, 93, 98, 126, 197
cytokines, x, 92, 95, 96, 98
cytoplasm, 22
cytotoxicity, 263, 278
Czech Republic, 200
D
dairy industry, 239
dairy products, xiv, 8, 9, 32, 38, 60, 75, 203,
234, 235, 239, 242, 251, 286
database, 81, 143, 146, 208
deaths, 57, 66, 84, 94, 262
decay, 21, 71
decontamination, 31, 32, 218
defects, 50
defence, 52
defense mechanisms, ix, 64
deficiency(s), 146, 197, 215
degradation, 4, 11, 12, 19, 49, 286
degumming, 245
demographic data, 129, 135
denaturation, 131
Department of Agriculture, 216
Department of Health and Human Services,
231
depth, 8
derivatives, 64, 80, 81, 202, 242
destruction, 19, 201, 217
detectable, 81, 100, 118, 145, 206, 207, 240,
248
detection, x, 9, 10, 13, 15, 18, 25, 29, 31,
34, 81, 86, 87, 107, 131, 132, 238, 239,
240, 241, 242, 244, 248, 251, 253, 254,
255, 257, 265, 276
detection system, 131, 132
detention, 219
detoxification, xiii, 5, 10, 11, 25, 29, 81,
192, 195, 274, 275, 283
developed countries, 81, 116, 117, 220
developing countries, xv, 2, 33, 57, 79, 81,
87, 88, 105, 117, 119, 193, 209, 210,
220, 223, 260, 261, 265, 266, 270, 271,
273, 274, 276, 279, 285
developing nations, 272
diarrhea, 79, 199
diet, 2, 80, 97, 99, 194, 201, 202, 203, 204,
222, 225, 236, 240, 242, 244, 266, 270,
273, 274
dietary habits, 202, 204
dietary intake, 80, 89, 206
digestibility, 199, 225, 267
digestion, 130, 195, 268
digestive enzymes, 197, 199, 267, 282
disease progression, 101
disease rate, 100
diseases, xv, 6, 36, 38, 53, 80, 98, 101, 198,
201, 210, 223, 224, 260, 270, 271, 276
disorder, 204
dispersion, 280
displacement, 271
disposition, 226
distillation, 11
distilled water, 22
distribution, 8, 65, 129, 132, 138, 160, 194,
204, 207, 239, 262
diversity, 172, 265
Index 292
DNA damage, xi, 102, 126, 127, 139, 147,
150, 151, 226, 266
DNA ligase, 143, 152
DNA polymerase, 152
DNA repair, xi, 93, 126, 127, 128, 132, 133,
137, 138, 139, 140, 141, 143, 145, 146,
147, 148, 150, 153, 154, 155, 156
DNA-adducts, xv, 139, 260, 266
DNase, 268
documentary evidence, 111
dogs, 5, 267
dominance, 174
dopamine, 200
dosage, 97, 248, 269
dosing, 97, 103
dough, 228
draft, 120
drought, 6, 7, 39, 40, 52, 56, 66, 67, 71, 165,
166, 185, 197, 264
drugs, 55, 215
drying, xii, 6, 11, 39, 58, 66, 67, 74, 108,
130, 158, 159, 171, 246, 250, 264, 279
E
East Asia, 272
ecology, 39, 41, 47, 61, 62
economic losses, 116, 262
economic problem, viii, 2, 10
economics, ix, 64
ecosystem, xi, 157, 180
edema, 79, 196, 272
education, 271
egg, 6, 79
Egypt, 42, 83, 244, 276
electron, 224
ELISA, vii, 2, 4, 9, 13, 14, 16, 17, 18, 21,
24, 26, 30, 34, 130, 234, 238, 240, 241,
247, 255
ELISA method, 13, 14, 16, 21, 24, 241
elucidation, 139, 148
e-mail, 259
encephalopathy, 200, 226
encoding, 143
endocrine, 6
energy, 5, 6, 159
enforcement, 81, 194, 214, 215, 216
engineering, 7
England, 3, 193, 262
environment(s), 6, 36, 45, 53, 65, 109, 166,
183, 214, 261
environmental conditions, viii, 33, 36, 39,
43, 48, 52, 60, 160, 165, 183, 248
environmental factors, ix, 5, 25, 47, 63, 66,
187, 235
environmental protection, 110
environmental stress, 48, 183
enzyme(s), xi, 10, 94, 98, 99, 126, 130, 197,
198, 200, 225, 226, 238, 268, 277
enzyme-linked immunosorbent assay, 130
epidemic, 276
epidemiologic studies, 80
epidemiology, 88, 103, 280
epilepsy, 200
epithelial cells, 283
epithelium, 199
equipment, 10, 244
ethanol, 22, 130
ethnicity, 129
eukaryote, 59
Europe, 71, 72, 102, 110, 113, 194, 200,
203, 209
European Commission, 70, 113, 114, 207,
210, 211, 229, 230, 237, 255, 266, 279
European Community, 12, 110, 246
European Parliament, 27, 28, 83, 253
European policy, 110
European Social Fund, 82
European Union, ix, x, 8, 27, 63, 64, 67, 68,
69, 70, 74, 82, 107, 113, 121, 122, 159,
185, 205, 210, 229, 248, 253, 266, 279
evaporation, 263
evidence, xiv, xv, 8, 79, 80, 81, 82, 94, 127,
129, 148, 198, 199, 205, 206, 215, 222,
234, 260, 270, 273, 274
evolution, 29, 195
examinations, 129
excision, 143, 146, 156
exclusion, 209
excretion, 34, 248
Index 293
exons, 143, 145, 146, 147
expertise, 244
exploitation, 110
export control, 82, 214
export market, 109
exporter(s), 119, 214, 231, 242
exports, 109, 110, 118, 209
expressed sequence tag, 62
extraction, 10, 11, 16, 57, 110, 129, 130,
238, 244, 245, 249, 265
extracts, 15, 26, 256
extrusion, 224
F
farms, 3, 7, 58, 241, 247, 248
FASAY, 151
fat, 2, 198, 242
fatty acids, 49, 51, 52, 55, 56, 186, 242, 250
FDA, xiii, 5, 28, 192, 215, 216, 217, 218,
219, 231, 268
feces, 92
federal agency, 215
feedstock, 5
feedstuffs, 8, 9, 75, 78, 194, 209, 214, 268
fermentation, 11, 204, 240
fetal development, 257
fetus, 201
fever, 79, 269, 272
fibers, 250
fibroblasts, 146, 155
filament, 144
financial, 101, 150, 276
financial support, 101
fish, xv, 6, 260, 265, 268
flagellum, 224
flavonoids, 249, 250, 257
flavor, x, 107, 108
floods, 261
flora, 5, 25
flotation, 11
flour, 43, 73, 77, 86, 87, 182
flowers, 64, 159
fluid, 30, 45, 238
fluid extract, 238
fluorescence, 10, 86, 193, 244, 249, 251,
255
food additive(s), 223
Food and Drug Administration, xiii, 192,
209, 215, 231
food chain, xii, xv, 28, 59, 66, 67, 84, 158,
202, 211, 235, 237, 261, 271
food industry, 194, 209
food intake, 77
food production, viii, 2, 10, 67, 81, 211,
248, 261
food products, 12, 28, 84, 202, 203, 207,
214, 218, 238, 246
food safety, vii, x, xiii, 1, 2, 8, 30, 45, 64,
74, 83, 88, 119, 122, 194, 209, 210, 211,
216, 218, 220, 224, 229, 231, 233, 237,
239, 248, 249
food security, 210, 220
foodborne illness, 216, 218
force, 8, 212
formation, viii, xi, xv, 2, 3, 18, 19, 25, 48,
52, 56, 60, 62, 93, 98, 126, 127, 139,
144, 159, 188, 197, 236, 260, 266
formula, 76, 221, 262, 264
France, 29, 58, 85, 202, 203, 254, 280
free radicals, 19, 104, 195
freezing, 66
fruits, ix, xiv, 63, 66, 69, 77, 81, 88, 108,
109, 120, 159, 202, 238, 245, 260, 267,
280, 284
Functional Analysis of Separated Alleles in
Yeast, 151
functional food, 119
funding, 219
fungal infection, 3, 57
fungus, xii, 36, 39, 40, 41, 47, 49, 53, 54,
60, 64, 92, 163, 165, 173, 181, 183, 189,
192, 197, 199, 240, 262
furan, 19
fusion, 127
G
gamma radiation, viii, 2, 26, 33, 54
gastrointestinal tract, 225, 262
Index 294
gene expression, 47, 99, 195, 286
gene regulation, 50
genes, vii, ix, xi, 36, 45, 46, 47, 48, 49, 50,
53, 61, 62, 126, 127, 128, 132, 133, 137,
138, 139, 140, 141, 148, 150, 151, 153,
155, 163, 195
genetic defect, 199
genetic engineering, 53
genetic mutations, 148
genetics, vii, ix, 36, 45, 46
genome, vii, viii, 36, 46, 53, 57, 102
genomics, 62
genotype, 61, 132, 135, 138, 139, 263
genotyping, 132
genus, vii, ix, xii, 1, 3, 18, 42, 63, 64, 71,
158, 168, 171, 172, 243, 262
Georgia, 61
Germany, 13, 14, 15, 188
germination, 19, 21, 40, 159, 163, 182, 256
gerontology, 155
ginger, xiv, 69, 92, 203, 260, 264
gland, 262
global scale, 246
globalization, 209, 239
glutamate, 200, 226
glutathione, 151, 225, 284
government intervention, 215
governments, 108, 119, 207, 276
grants, 184
Great Britain, 188, 189
Greece, vi, xiii, 191, 233, 235, 236, 237,
238, 239, 240, 242, 243, 244, 245, 246,
247, 248, 249, 250, 251, 255, 256, 257
green olives, xiv, 234, 236, 254
growth rate, 6, 21
Guangdong, 147
guanine, 93, 99, 102, 103, 151, 197
guidance, 194, 215, 216, 230
guidelines, 210
Guinea, 284
Guyana, 108
H
half-life, 21, 80
haplotypes, 154
harmful effects, viii, 2, 8, 25
harmonization, 74, 222
harvesting, xiv, 3, 4, 6, 7, 10, 53, 74, 159,
234, 238, 245, 256, 273
hazards, vii, xiv, 30, 31, 71, 199, 204, 210,
235, 237, 258, 260, 265, 266
HBV, 94, 101, 128, 129, 135, 136, 138, 141,
142, 156, 206, 270
HBV infection, 94, 101, 138
HCC, xi, xv, 93, 94, 101, 126, 127, 128,
129, 130, 132, 135, 136, 137, 138, 139,
141, 143, 144, 145, 146, 147, 148, 149,
197, 260, 267, 269, 270
health care, 37, 116
health effects, x, 64, 68, 81, 193, 194, 195,
201, 204, 211, 215, 224, 226, 238, 242,
251, 270, 271, 274, 275
health problems, 237, 266
health risks, 74, 211, 237, 266
health services, 276
hematemesis, 79
hemorrhage, 79
hepatic encephalopathy, 281
hepatic failure, 269
hepatic necrosis, xv, 260, 266
hepatitis, 6, 79, 80, 82, 103, 129, 152, 206,
207, 227, 269, 270, 272, 274, 278, 281,
282, 284
hepatitis a, 79
hepatitis b, 272
hepatitis c, 207, 282
hepatocarcinogen, 92
hepatocarcinogenesis, xv, 103, 260, 284
hepatocarcinoma, ix, 64
hepatocellular carcinoma, xi, xv, 6, 33, 57,
80, 82, 93, 94, 105, 126, 127, 128, 149,
151, 152, 154, 155, 156, 197, 260, 267,
271, 272, 276, 282, 284, 285
hepatocytes, 79, 152, 196, 222, 254
hepatoma, 267
hepatotoxicity, 79, 222, 263, 269
hepatotoxins, xv, 260, 268
herbal medicine, 186, 280
heterogeneity, 102
Index 295
heterozygote, 135
histone(s), 46, 49, 99
history, 129, 164, 211, 225
HIV, xv, 80, 98, 100, 101, 260, 270, 273
HIV/AIDS, xv, 80, 260, 270
homeostasis, 95, 96, 199
homozygote, 137, 138, 144, 145, 149
hormone, 198
host, ix, x, 36, 38, 49, 50, 53, 54, 56, 58, 92,
101, 266
human body, 195, 202
human exposure, 68, 80, 88, 201, 204, 241
human health, viii, 8, 9, 10, 35, 38, 87, 212,
214, 215, 223, 224, 235, 237, 239, 249,
258, 262, 270, 276
human immunodeficiency virus, 103
humidity, 2, 7, 8, 18, 45, 56, 65, 67, 109,
173, 202, 243, 247, 250, 261
humoral immunity, x, 91, 100, 201
hydrogen, 19, 95
hydrogen peroxide, 19, 95
hydrolysis, 93
hydrophobicity, 55
hygiene, 111, 119, 246
hyperplasia, xv, 260, 266
I
icterus, 196
ID, 103, 123, 145, 146, 231
identification, 46, 53, 62, 111, 168, 193,
204, 223, 265
IFN, 95, 97
immune function, 33, 105, 227, 272, 285
immune response, x, 92, 95, 100, 103
immune system, 6, 82, 101, 199, 266, 268,
274
immunity, x, xiii, 79, 91, 99, 100, 192, 193,
194, 195, 200, 201, 225, 267, 270, 273
immunoglobulin, 153
immunomodulatory, x, 91, 100
immunosuppressants, xv, 260, 268
immunosuppression, x, xv, 91, 101, 260,
266, 270
impaired immune function, 272
impairments, 6
import restrictions, 113
imported products, 114, 219
imports, 71, 112, 209, 214, 250
improvements, 3
in utero, 81
in vitro, 21, 23, 95, 96, 97, 98, 100, 104,
189, 193, 206, 278, 281
in vivo, 23, 95, 97, 100, 104, 206, 263
incidence, ix, xv, 2, 64, 70, 71, 73, 79, 80,
82, 94, 101, 110, 114, 118, 147, 160,
163, 171, 172, 180, 181, 182, 186, 196,
206, 260, 270, 273
income, 70
incubation period, 172, 180
incubation time, 57
independent variable, 135
India, 33, 43, 77, 182, 189, 203, 220, 221,
223, 230, 259, 281
indirect effect, 109
individuals, x, 6, 92, 98, 101, 138, 145, 206,
265, 273, 274
Indonesia, 76, 173
inducer, 49, 51, 55
induction, ix, 61, 64, 77
industry(s), 11, 25, 88, 110, 121, 186, 211,
216, 238, 241
infancy, 266
infants, 37, 69, 76, 77, 214, 221
infection, x, 7, 36, 40, 41, 44, 55, 56, 58, 88,
92, 94, 96, 98, 100, 101, 129, 135, 138,
156, 163, 164, 165, 166, 173, 201, 206,
227, 268, 272, 273
infectious agents, 80
infertility, 198, 224
infestations, 261
inflammation, x, 92
informed consent, 129
infrastructure, 119
ingest, 262
ingestion, ix, 4, 6, 63, 64, 78, 79, 193, 204,
225
ingredients, 8, 38, 54, 78, 217, 247, 264
inhibition, 19, 22, 23, 198, 255, 256
initiation, 7
Index 296
injury, 172
inoculation, 39, 41, 244
inoculum, 3, 39, 40, 41, 59, 163, 168, 183,
186
insects, 6, 36, 40, 44, 182, 187
insomnia, 200
inspections, 216
integrity, 112
inter kingdom communications, ix, 36
interference, 36, 193, 200, 266, 270
international standards, 110
international trade, 68, 108, 210
intervention, 115, 116, 276, 285
intervention strategies, 276
intoxication, 6, 116, 195
introns, 143, 145, 146, 147
investment, 119
ionization, 12, 16
ionizing radiation, 30, 33
ions, 17
Iowa, 278
Iran, 37, 60, 116, 122, 199, 252, 253, 256
Ireland, 91, 101
irradiation, 11, 12, 19, 20, 21, 27, 31
irrigation, 52, 56
ischemia, 226
isolation, xii, 41, 157, 160, 163, 168, 171,
176, 238
issues, 8, 210, 216, 219, 220, 225, 266
Italy, 28, 45, 73, 87, 191, 222, 228, 241,
242, 244, 255, 256
J
Japan, xiii, 58, 61, 76, 155, 192, 203, 220,
228
jaundice, 79, 269
justification, 110
K
Kenya, 30, 57, 58, 71, 73, 78, 83, 84, 86,
166, 182, 183, 187, 196, 199, 221, 223,
271, 278, 282
kidneys, 79
kinetic parameters, 225
Korea, 76, 77
Kuwait, 78, 84, 220
L
lack of confidence, 117
lactation, 83, 89, 262
lactic acid, viii, 2, 4, 11, 23, 24, 27, 28, 29,
32, 240
Lactobacillus, 23
laws, 216
LC-MS/MS, vii, 2, 4, 13, 15, 16, 17, 54,
123, 234, 238, 244
lead, 3, 4, 41, 49, 53, 66, 79, 100, 143, 151,
155, 197, 198, 211, 242, 243, 245, 261,
270
learning, 200
legislation, vii, 32, 67, 74, 111, 113, 114,
115, 182, 194, 210, 211, 214, 215, 219,
230, 249, 258
legs, 79
Lepidoptera, 61
lesions, 93
leukemia, 155, 156
leukocytes, 136, 137
light, 12, 47, 48, 54, 61, 82, 85, 92, 200,
215, 224, 262
linoleic acid, 51, 57, 236
lipases, 197, 236
lipid oxidation, 236
lipid peroxidation, 198
lipids, 79, 249
liquid chromatography, vii, 2, 4, 10, 34, 54,
73, 86, 234, 238, 244, 252, 255, 256,
257, 265, 280
liver cancer, ix, xv, 5, 64, 78, 80, 82, 85,
102, 128, 151, 152, 197, 205, 206, 207,
222, 223, 260, 266, 272, 279, 280, 283
liver cells, 196
liver cirrhosis, ix, 64, 135, 196
liver damage, ix, xv, 64, 79, 80, 195, 260,
266, 267, 271, 272
liver disease, 129, 148, 273
Index 297
liver failure, 197, 272
livestock, xiii, xv, 6, 65, 192, 260, 264, 268,
278
local government, 129
localization, 29
loci, 128
logistics, 67
longitudinal study, 85, 224, 279
Louisiana, 125
lovastatin, 49, 51, 57, 60
low risk, xi, 108
LSD, 178
lung cancer, 80, 153
lymph node, 155
lymphocytes, 95, 97, 99, 101, 102, 103, 146
lymphoid, 99
lysine, 93, 99
lysis, 100, 198
M
Macedonia, 191, 233
macrophages, xv, 95, 96, 100, 102, 104,
200, 260, 268, 281
magnitude, 196
majority, 194, 204, 238, 244, 248, 266
malaise, 79, 269, 272
malaria, xv, 80, 199, 201, 227, 260, 270
Malaysia, 43, 76, 200, 281
malignancy, 197
malignant tumors, 143, 145, 146
malnutrition, xv, 80, 116, 197, 199, 260,
266, 270, 272
mammalian cells, 154
mammals, 3
management, 39, 43, 57, 88, 117, 119, 150,
218
manufacturing, 3, 74, 114, 118, 221
market access, 183
marketing, 81, 110, 267
marketing strategy, 110
mass, vii, 2, 4, 10, 16, 54, 87, 234, 238, 244,
252
mass spectrometry, vii, 2, 4, 10, 16, 54, 87,
234, 238, 244, 252
materials, 7, 12, 13, 19, 21, 28, 62, 66, 237
matrix(s), 15, 266, 280
MB, 155
measurement(s), 15, 25, 31, 80, 81
meat, xiv, 4, 23, 26, 29, 30, 74, 83, 85, 86,
216, 260, 264, 267
media, 24, 28, 44, 227
median, 196
medical, 69, 73, 81, 129, 221, 249
medical history, 129
medicine, 154
Mediterranean, 236, 237, 240, 241, 242,
243, 244, 245, 246, 247, 251, 253
Mediterranean countries, 237, 240, 241,
243, 244, 245, 251
melon, 43
memory, 200
meristem, 40
meta-analysis, 144, 152, 153, 154
metabolic, 94
metabolic disorder(s), 30
metabolism, ix, xiii, 31, 36, 48, 50, 52, 64,
85, 103, 148, 192, 193, 195, 196, 198,
206, 254, 268, 275, 279, 280
metabolites, vii, ix, x, xii, 1, 3, 5, 11, 38, 47,
51, 63, 64, 80, 81, 91, 92, 94, 96, 99,
102, 105, 123, 158, 159, 174, 192, 193,
196, 235, 262, 264
metabolized, xi, 98, 126, 197, 239
metals, 48
metastasis, 129, 155
methanol, 14
methodology, 8, 180, 204, 205, 218
Mexico, 39, 58, 71, 78, 219, 221
mice, 98, 151, 198
microbiota, 60, 79, 199, 249
micronutrients, xiii, 192, 193
microorganism(s), 6, 11, 21, 37, 172
microscopy, 61
minicolumn, 265
mission, 110, 111, 112
Missouri, 40, 286
misuse, 222
mitochondria, 198
mitosis, 197
Index 298
modelling, 44, 208
models, 43, 103, 267
modifications, xiv, 46, 49, 234
moisture, 6, 7, 11, 13, 31, 36, 44, 67, 70, 71,
159, 173, 182, 186, 187, 243, 246, 247,
261, 282
moisture content, 7, 11, 13, 31, 44, 70, 159,
173, 246, 282
mold(s), 31, 60, 83, 87, 89, 159, 182, 184,
197, 226, 243, 244, 245, 247, 249, 257,
258, 274
molecular weight, 23
molecules, ix, 36, 37, 51, 52, 53, 94, 96, 99,
101
monoclonal antibody, 29, 30, 130
Moon, 95, 96, 104
morbidity, 198
Morocco, 243, 244, 247, 258
morphogenesis, 50
morphology, 51, 52, 151, 189, 198, 199,
283
mortality, 198, 272, 276
mortality rate, 272, 276
motif, 46
mould spores, 21
Mozambique, 95
MR, 101, 105, 156
mRNA, 95, 97, 98, 102, 156
multilateralism, 210
mung bean, 77, 220
mutagenesis, 48, 156
mutant, xi, 50, 52, 126, 132, 137, 139, 146,
148
mutation(s), xi, 12, 93, 102, 105, 126, 127,
128, 131, 135, 138, 139, 143, 145, 146,
147, 148, 149, 151, 152, 153, 156, 197,
222, 223, 266
mycelium, 22, 168, 170, 171
mycology, 61
myeloid cells, 99
N
naphthalene, 186
native isolates, 163
native population, 163
near infrared spectroscopy, 253
nebulizer, 16
necrosis, xv, 79, 196, 197, 260, 267
neonates, 239
Nepal, 43
nerve, 200
nervous system, 200
Netherlands, 72, 187, 189, 209
neurodegeneration, 226
neurogenesis, 146
neurons, 146
neurotoxicity, 193
neurotransmitter(s), 200
neutrophils, 97, 104
New Zealand, 78, 200, 203, 219, 220
Nigeria, 26, 43, 78, 219, 220, 224, 230, 256,
277
NIR, 257
nitric oxide, 95, 104
nitrite, 83
nitrogen, 45, 48, 56, 129
NMDA receptors, 200
nodes, 129
North Africa, 245
North America, 71, 81
nucleoprotein, 144
nucleus, 166
nutrient(s), 6, 11, 33, 36, 40, 159, 174, 199,
225, 267, 268, 270, 274
nutrition, 2, 82, 198, 199, 211, 222, 253,
273
nutritional deficiencies, 266
nutritional status, xv, 5, 260
O
officials, 267
oil, xiv, 22, 32, 43, 75, 89, 119, 242, 243,
244, 245, 246, 260, 265, 280
oil samples, 243, 244
oilseed(s), viii, xiv, 27, 35, 39, 49, 60, 66,
68, 69, 213, 230, 235, 260, 264, 266
oleic acid, 49
Index 299
olive oil, 236, 238, 242, 243, 244, 245, 246,
251, 252, 253, 254, 256, 257
operations, 3
optimization, 245
organ(s), 79, 127, 195, 197, 210, 225, 226,
283
organism, 48, 196
ox, xiv, 49, 52, 259, 261
oxidative stress, 154
oxygen, 45
oxylipins, ix, 36, 49, 50, 51, 52
ozone, 123
P
p53, 127, 138, 139, 143, 151, 152, 197, 222,
223
pain, 79, 196, 269, 271, 272
Pakistan, 58, 73, 83, 86, 87, 89, 281
parasite(s), 4, 80
parasitic infection, 200
participants, 98
pasta, 72
pasteurization, 38
pasture, 8, 38
pathogenesis, ix, 36, 49, 54, 280
pathogens, 36, 50, 53, 86
pathology, 32, 280
pathways, 49, 52, 99, 266
PCR, 87, 131, 132, 133, 134, 138, 147, 149,
174, 180, 188, 195
peanut meal, 3, 12, 19, 33, 75, 193
penicillin, 49, 51
peptide, 53
peripheral blood, 128, 129, 130, 136, 137,
139
peripheral nervous system, 200
peroxide, 14, 245
Peru, 108
pesticide, 53
pests, 61, 261
pH, 14, 23, 44, 47, 48, 59, 66, 67, 92, 130,
131, 171, 240
phagocytosis, x, 92, 98, 100, 200
phenol, 130
phenolic compounds, 245, 252
phenotype(s), xii, 50, 157, 160, 164, 271
Philippines, 39, 41, 43, 58, 60
phosphate, 14, 131
phosphorus, 268
physical properties, 171, 178, 264
physiology, 49
pigs, 5, 26, 75, 76, 79, 96, 99, 100, 227, 267
pistachios, ix, 5, 30, 63, 66, 68, 69, 70, 71,
76, 78, 82, 84, 92, 113, 116, 121, 202,
207, 208, 212, 220, 222, 229, 235, 250
placenta, 139, 151, 201
placental barrier, 199
plant growth, 40, 190
plants, viii, 4, 26, 32, 35, 36, 37, 40, 41, 42,
44, 49, 50, 53, 54, 58, 64, 73, 87, 159
plasma membrane, 198
platinum, 153
point mutation, 153
poison, 262
Poland, 173, 184
polarity, 16
policy, 210, 211, 215, 216, 218, 220
pollen, 40, 236, 238, 249, 252, 256
pollutants, 257
polymerase, 149, 195
polymerase chain reaction, 149
polymorphism(s), xi, 126, 127, 132, 133,
138, 143, 144, 145, 146, 147, 148, 150,
151, 152, 153, 154, 155, 156, 284
polyphenols, 242
polypropylene, 173
population density, 52
population group, xiv, 207, 234
population growth, 261
population structure, 188
Portugal, 107, 242, 253, 255, 281
positive correlation, 44, 179, 183
positive relationship, 40
poultry, xv, 3, 6, 74, 78, 79, 86, 201, 217,
247, 254, 256, 258, 260, 264, 268, 286
poverty, 110
poverty reduction, 110
pregnancy, 228
preparation, 13, 81
Index 300
preparedness, 275
present value, 240, 251
preservation, 245
prevention, viii, 2, 10, 19, 25, 28, 32, 33, 85,
121, 148, 152, 218, 274, 280, 284
principles, 118, 211, 212, 229
private sector, 116
probability, xi, 44, 157, 204, 205, 228
probe, 131, 132
probiotic, 23, 24, 29
producers, 36, 37, 42, 44, 70, 108, 109, 118,
162, 164, 165, 168, 176, 179, 182, 211,
216, 218, 250
productive efficiency, 26
progenitor cells, 97
pro-inflammatory, 95, 100
proliferation, xv, 21, 89, 97, 195, 260, 261,
267
promoter, 46
prophylactic, 274
prostate cancer, 152, 155
protection, xi, 22, 25, 52, 108, 111, 113,
194, 211, 218, 250, 261
protein synthesis, 6, 198, 199, 200
proteinase, 130
proteins, xv, 47, 48, 49, 52, 93, 99, 146,
196, 250, 260, 266, 273
public concern, 53
public health, xv, 32, 84, 111, 112, 113,
116, 121, 194, 205, 208, 209, 212, 214,
215, 219, 221, 246, 260, 267, 269, 270,
271, 276, 285
pulmonary edema, 79, 271
purification, 244
P-value, 135
pyridoxine, 197
Q
quality control, 122, 131, 132, 237
quality standards, 218, 248
quantification, 9, 10, 17, 87, 180, 188, 238,
241, 265
questionnaire, 129, 130
R
race, 128, 129, 135, 138, 141, 142
radiation, 4, 12, 19, 21, 25, 26, 28, 89
radicals, 19
rain forest, 108
rainfall, 38, 160, 164
rainforest, 108
raw materials, 4, 247
RE, 103
reactions, 151, 195
reactive oxygen, 96, 105
reagents, 9
reasoning, 194
recall, 219
recognition, 147
recombination, 144, 153, 154, 155
recovery, 9, 13, 14, 15, 16
recurrence, 156
regions of the world, 8, 209, 235
regression, 135, 139
regression analysis, 139
regression model, 135
regulations, vii, x, 8, 28, 64, 70, 74, 79, 82,
87, 88, 113, 119, 159, 182, 194, 204,
209, 210, 214, 216, 218, 219, 237, 249,
273
regulatory framework, xiii, 192
rejection, 115, 116, 119
relative size, 144
relaxation, 113
relevance, 201
reliability, 112
repair, xi, 102, 126, 127, 138, 139, 143, 145,
146, 148, 149, 150, 151, 152, 154, 155,
156
repression, 60
reproduction, 52, 58, 278
requirements, 10, 199, 211, 229
researchers, 42, 139, 147, 173
residues, xiv, 12, 53, 93, 99, 146, 203, 227,
234, 238, 240, 241, 242, 251, 257
resistance, 53, 55, 56, 83, 163, 181, 184,
278
resolution, 10
Index 301
resources, 116, 205, 261, 271, 276
respiration, 6
response, 77, 95, 96, 97, 99, 101, 103, 104,
114, 154, 155, 201, 205, 208, 211, 225,
275, 276
response capacity, 276
restrictions, 112
retail, 211, 244
retardation, 267, 270
reticulum, 195
retina, 226
RH, 173, 250
Rhizopus, 168, 169, 170, 171, 173, 182
risk assessment, vii, xiii, 8, 113, 118, 122,
192, 194, 204, 205, 208, 210, 228, 235,
238, 241, 242, 251, 257, 273
risk factors, 255, 269, 272
risk management, xiii, 192
risk perception, 220
RNA, 195, 200, 266
rodents, 6, 182
room temperature, 250
roots, 40
routes, 273
rubber, 110
rules, 212, 214, 219, 230
S
safety, xiv, 12, 67, 74, 119, 120, 209, 210,
211, 212, 215, 218, 221, 231, 234, 239,
245, 246, 251
saliva, 201
salts, 283
samplings, 175, 178, 179
Saudi Arabia, 25, 78, 220
schistosomiasis, 151
schizophrenia, 156
school, 71
science, 210, 223, 267
scope, 10, 211, 216
secondary metabolism, vii, ix, 36, 45, 46,
47, 48, 49, 50, 53, 54, 55, 58, 60, 62
secretion, x, 92, 95, 96, 97, 98, 100, 102,
201
security, 27, 210
seed, viii, 19, 35, 39, 40, 49, 51, 52, 54, 58,
61, 108, 115, 159, 167, 170, 172, 173,
175, 178, 180, 181, 185, 187, 189, 230,
245, 251
seeding, 164
selectivity, 186
selenium, 119, 151, 250
semen, 198
sensations, 200
sensing, ix, 36, 48, 50, 51, 52, 53, 60, 61
sensitivity, 10, 98, 199, 244
sequencing, vii, viii, 36, 46, 132
Serbia, 203, 228
serine, 94, 99, 102
serotonin, 200, 226
serum, 80, 81, 98, 105, 129, 136, 201, 206,
267, 268, 271, 277, 283
services, 231
sex, 80, 128, 129, 135, 138, 141, 142, 147,
151, 195, 198
sexual development, 55
SGOT, 268
SGPT, 268
sheep, 4, 24, 79, 241, 248, 252
showing, 127, 163, 171, 172, 175, 214, 265
sibling, 59, 87
signalling, ix, 36, 47, 49, 50, 52, 94, 99, 101
signals, 50, 92
signs, 79, 267, 271
silk, 39, 40, 41
Singapore, 75
sister chromatid exchange, 283
Slovakia, 200
small intestine, 193, 222
SNP, 143, 146, 153
socioeconomic status, 198
sodium, 12, 32, 281
software, 15
soil type, 263
solution, xv, 13, 15, 16, 19, 23, 119, 131,
261, 271
solvents, 10, 11, 238
South Africa, 71, 78, 220, 221, 228
South America, 39, 71
Index 302
sowing, xii, 158, 160, 165, 186
soy bean, 8, 127
soybeans, 77
SP, 152, 155, 189
Spain, 63, 72, 82, 88, 89, 202, 228, 241,
242, 243, 244, 250, 252, 254
specific gravity, 109
spectroscopy, 234, 238
sperm, 198, 224
spleen, 97
spore, 7, 50, 71
SS, 105, 156
stability, 84, 240, 254, 279
stakeholders, 70, 267
standard deviation, 13, 17
standard error, 177, 178
starvation, 57, 79, 84
state(s), 8, 9, 32, 47, 58, 70, 116, 184, 243,
271
statistics, 276, 282
stereospecificity, 225
sterigmatocystin, ix, 36, 38, 46, 47, 48, 49,
50, 55, 86, 280
sterile, 12, 56, 168, 172
stimulation, 96, 97
stress, xii, 39, 52, 56, 66, 71, 158, 165, 166,
168, 264
stressors, 5
structural gene, 46
structure, 10, 24, 44, 50, 62, 190, 223, 235
style, 244, 253, 257
styrene, 186, 280
sub-Saharan Africa, 80, 270
subsistence, 273
substitution, 143
substrate(s), viii, xii, xiv, 7, 10, 14, 21, 35,
39, 49, 65, 66, 158, 163, 181, 234, 236,
238, 243, 245, 249, 250, 255
succession, xii, 158, 173
sucrose, 22
Sudan, 43
sulfate, 12
sulfuric acid, 14
Sun, 153, 266, 284
supplementation, 57
suppliers, 211, 219
supply chain, 27
suppression, xv, 6, 52, 80, 260, 267, 269,
270, 271, 273
surface component, 24
surveillance, 207, 250, 271, 275, 276
survival, 22, 26, 184, 279
susceptibility, ix, x, 5, 6, 30, 64, 80, 92, 100,
104, 143, 147, 152, 153, 154, 155, 200,
265, 267, 271, 273, 284
sustainability, 122, 214
sustainable development, 210
Sweden, 13, 72
Switzerland, 33, 219
symptoms, xiii, 6, 79, 192, 197, 198, 200,
268, 269, 271, 272, 283
syndrome, 80, 268
synergistic effect, 96, 256, 274
synthesis, vii, ix, 36, 46, 47, 81, 185, 195,
198, 200, 242
T
T cell(s), 97, 98, 100, 201
T regulatory cells, 98
Taiwan, 155, 278, 284, 285
tannins, 189
target, xv, 3, 10, 48, 79, 100, 195, 260, 267
tariff, 110
TDI, 79
teams, 148
techniques, vii, viii, xiv, 2, 7, 36, 46, 138,
195, 202, 204, 234, 236, 238, 239, 244,
251, 265
technology, 25
telomere, 45
teratogenic effects, ix, xv, 64, 77, 260, 266
testing, 119, 218
testosterone, 80, 195
tetrahydrofuran, 92
TGA, 131
Thailand, 37, 39, 41, 43, 57, 60, 61, 200,
203
therapy, 274
thermal stability, 66
Index 303
Third World, xiii, 192
threats, 52
thymus, 131
tissue, 58, 95, 128, 129, 135, 138, 139, 168,
197
tissue homeostasis, 95
TLR4, 96
TNF-, 95, 97, 98
tocopherols, 186
Togo, 81, 85, 198, 224, 270, 279
total product, 108
toxic effect, ix, 5, 38, 64, 93, 102, 143, 147,
194, 195, 196, 281, 284
toxic products, 10
toxicity, xiii, 3, 5, 19, 25, 32, 33, 37, 64, 77,
79, 80, 97, 99, 102, 151, 192, 193, 194,
195, 196, 198, 199, 248, 255, 262, 273,
285
toxicology, vii, 88, 105, 150, 223, 224, 226,
285
toxigenic fungi, viii, 35, 36, 42, 55, 60, 86,
109, 243
toxin, viii, xi, xv, 2, 3, 9, 10, 11, 22, 23, 35,
37, 38, 44, 53, 55, 66, 73, 89, 126, 127,
143, 147, 148, 164, 178, 179, 199, 216,
235, 246, 260, 266, 275, 276, 283
TP53, xi, 126, 127, 128, 131, 145, 148, 149,
151
trade, 8, 37, 110, 116, 119, 120, 202, 209,
210, 215, 220, 267
trade liberalisation, 210
trade policy, 120
traits, 86, 187
transcription, 47, 48, 50, 59, 60, 146, 195
transcription factors, 47
transduction, 104
transformation, 137, 153
translation, 195
transmission, 224, 273
transparency, 211, 219
transplant, 53
transport, 4, 7, 47, 66, 74, 111, 159
transportation, 67
traumatic brain injury, 226
treatment, 12, 68, 69, 95, 96, 97, 98, 197,
212, 224, 226, 245, 249, 257, 275
tremor, 200
trial, 257, 274
triggers, 96
trypsin, 268
tryptophan, 200, 226
tuberculosis, 273
Tukey Test, 167
tumor(s), ix, 64, 129, 135, 139, 143, 152,
155, 197, 200, 222, 223
tumor cells, 155
Turkey, 43, 72, 73, 87, 92, 193, 219, 221,
267, 284
turnover, 7, 199
tyrosine, 200, 226
U
U.S. Department of Agriculture, 231
United Kingdom (UK), 66, 103, 105, 272,
285, 286
United Nations, x, 64, 84, 186
United States, xiii, 38, 95, 185, 192, 200,
202, 231, 267, 285
urea, 12, 14
urine, 5, 27, 34, 80, 81, 92, 93, 102, 103,
271
USDA, 217
UV, 29
UV light, 37
V
vaccinations, 100, 271
vaccine, 100, 104, 201
validation, 13, 14, 15, 103, 253
variables, 132, 135, 204
variations, 5, 83, 89, 100, 173, 179, 194,
204
varieties, 190, 242, 243, 244, 274
vector, 187
vegetable oil, 27, 68, 81, 230, 256
vegetables, 72, 229, 280, 284
Index 304
Venezuela, 108, 200
ventilation, 67
vertebrates, 193
virus infection, 272, 282
viruses, 85, 152, 279, 284
visualization, 37
vitamin A, 273
vitamin E, 223, 273
vitamin K, 200
vitamins, 159, 249, 250
vomiting, xiii, 79, 192, 196, 269, 271, 272
vulnerability, 81
W
Washington, 27, 61
water, xii, 6, 7, 14, 16, 19, 21, 37, 44, 48,
57, 58, 59, 65, 66, 67, 158, 168, 184,
185, 188, 235, 253, 256
weight gain, 267
weight loss, 6, 79
welfare, 230
well-being, 37
wells, 14, 131
West Africa, 81, 85, 102, 189, 204, 224,
277, 279, 284
wheat germ, 89
White Paper, 211, 229
wild type, 51, 135
wood, 19
workers, 80, 194, 209
World Health Organization (WHO), x, 8,
12, 28, 29, 32, 33, 42, 62, 64, 85, 86,
120, 205, 207, 210, 223, 224, 226, 229,
254, 267, 272, 282, 285
World Trade Organization (WTO), 210,
212, 222
worldwide, ix, x, xiv, xv, 5, 38, 52, 63, 64,
73, 74, 79, 82, 84, 94, 159, 202, 214,
239, 260, 265, 266, 270, 275, 276
X
xeroderma pigmentosum, 149, 156
Y
yeast, 22, 26
Yemen, 78, 220
yield, 26, 45, 206, 207
young people, 80
Z
zinc, 57