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Induction of oxidative stress and cancer

Reactive oxygen species also can interact with nuclear DNA to form 8-deoxyguanosine or 06-methylguanine, which are indicative of oxidative damage to DNA. Formation of 8-deoxyguanosine is associated with mutations resulting from G T transitions, so reactive oxygen species may ultimately induce tumor formation. Therefore, oxidative DNA damage is considered a prominent non-genotoxic mechanism in determining the tissue specific risk of cancer development. This type of non-genotoxic mechanism has been proposed for ochratox-in A and fumonisin Bj, whereas aflatoxins can induce mutational events directly since its In farm animals, the induction of cancer by mycotoxins is rarely seen, with the exception of liver cancer induced in fish species by aflatoxins, as during the relatively short life span of these animals, neoplastic lesions are not of clinical importance.

Cancer Risks

The incidence of cancer in veterinarians is generally low, in part due to the low prevalence of cigarette smoking in this group. However, they come into contact with several potentially carcinogenic exposures including radiation, anesthetic gases, pesticides, and zoonotic agents. Other sources of carcinogenic exposure are solar radiation, veterinary pharmaceuticals, and office and laboratory chemicals (25). Veterinarians have elevated risks for several specific cancer types including leukemia, Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, and cancers of the lip, stomach, prostate, brain, and connective tissue. Two major groups of risk factors have been proposed as causes of hematological malignancies in agricultural workers. The first group includes various agricultural chemicals. In particular, several studies have found increased risks of malignant lymphoma and soft tissue sarcoma in persons exposed to phenoxy herbicides. However, the evidence is inconsistent, and...

Childhood Cancer

Although there is no strongly consistent evidence, a number of studies have found associations between childhood cancer and parental agricultural occupations or exposures. A large international study found associations between childhood brain tumors and various farm-related activities including maternal exposure to farm animals, working on a farm and pesticide exposure. In the same study, maternal exposure to pigs was associated with a 4-fold increase in risk of primitive neuroectodermal tumors. Other studies have found similar results. Chemicals, such as those found in a farm environment, and microbes that could be found in farm animals have been hypothesized to Occupational parental pesticide use is associated with leukemia, childhood brain cancer, Wilm's tumor, and Ewing's sarcoma. Use of pesticides in gardens has been associated with childhood leukemia in Northern Germany and other countries. Other studies have found no association with paternal exposures to pesticides and...

Occupational Risk from Methods to Increase Food Safety Use of Pesticides and Chemicals

Exists for potential chronic health effects of exposure to several pesticide classes at chronic low levels such as the association of chronic neurological effects with exposure to several pesticide classes. Examples include the association of increased vibration sense, motor-sensory neuropathy, and cognitive and affective deficits after exposure to organophosphates the association of olfactory, cognitive, and behavioral deficits after exposure to methylbromide and the association of symptoms of Parkinson's disease after paraquat exposure. Another example is association of oligospermia and azoospermia after exposure to dibromochloropropane (DBCP), which is now banned in the United States. There is also evidence of associations of chronic low-level exposure to pesticide residues and cancer (5,6,53-56). A major area of interest in relation to pesticides and cancer has concentrated on pesticides acting as endocrine disrupters, mostly organochlorinated insecticides, and on hormone-related...

Activities Investments and Values

Biologists argue that the extinction of a species imposes losses on humans. Two distinct effects are noted. First, an extinct species is 'lost' for future use, in the sense that its genetic materials cannot be put to utilitarian purposes. If a species is extinct, we can never know whether it might have offered a cure for cancer or - more prosaically - a gene that could be used in crop improvement. Second, the loss of any species can perturb the delicate ecological balance of a natural system. This in turn can cause damaging effects for humans.

Herbicides and water quality

Since the 1980s there has been increasing recognition that herbicides, applied in the course of normal farming practices, have contaminated surface and ground water in many agricultural regions (Barbash et al., 1999 Larson, Gilliom & Capel, 1999 United States Geological Survey, 1999). Among the herbicides detected most frequently in drinking-water sources, there are a number of compounds classified as probable (e.g., acetochlor), likely (e.g., alachlor), and possible (e.g., atrazine, cyanazine, metolachlor, and simazine) carcinogens (United States Environmental Protection Agency, 1999). Several herbicides contaminating drinking-water sources are also under scrutiny as possible disrupters of human immune, endocrine, and reproductive systems (see section Acute and chronic effects of herbicides on human health below). The effects of low-level exposure to herbicides are poorly understood, but there is considerable popular and regulatory concern over contamination of drinking-water...

Pauline E Jolly Yi Jiang William O Ellis Jia Sheng Wang Evans Afriyie Gyawu Timothy D Phillips and Jonathan H Williams

Aflatoxins are a group of secondary metabolites produced by strains of some Aspergillus species, mainly A. flavus and A. parasiticus (Gourama and Bullerman, 1995). These compounds are potent carcinogens found in crops such as maize, groundnuts, legumes and other grains that form the staple diet in many developing countries (Cardwell, 2001). Among the aflatoxin chemotypes (B1, B2, G1 and G2), B1 is the most common and toxic form (Park et al., 2002). Aflatoxin M1 is a hydroxylated metabolite of aflatoxin B1 found in the milk and urine of humans or other mammals that consume a diet contaminated with aflatoxin B1

Mechanism of the immunomodulatory effects of mycotoxins

The data of Marin et al. (2002) and Jiang et al. (2005) support previous conclusions (Pier, 1986) that total T cell populations of peripheral blood lymphocytes are not affected by oral consumption of aflatoxin. However, the alterations in the different lymphocyte subsets and their cytokine secretions found by Jiang et al. (2005) and the significant decrease in secretory IgA found by Turner et al. (2003) indicate impairment in cellular and humoral immunity in people (adults or children) chronically exposed to aflatoxin in their diets. These individuals had accumulated high levels of aflatoxin B1-albumin adducts in their blood, and based on the immune results are expected to have decreased resistance to infection and cancer (supported by the association between aflatoxin with hepatocellular carcinoma), decreased immune responses to vaccines, and increased susceptibility to reactivation of chronic infections.

Food safety and human health

There are several areas of public concern with regard to potential human health risks of GM foods. These relate to understanding the potential of proteins and or other molecules in GM foods to cause allergic reactions, to act as toxins or carcinogens and or to cause food-intolerance reactions among the population. Methods of testing and evaluating these types of risks have been established for food and these are being applied to GM foods so as to detect any increased risks associated with particular foods (Lehrer, 2000).

Socioeconomic impacts of aflatoxin contamination Impact on nutrition health and environment

Aflatoxins are among the main food contaminants with significant negative impact on health, food and nutritional security and incomes at the household, community and national levels. Food contaminated with aflatoxins may result in fatal aflatoxicosis and chronic mutagenic and carcinogenic effects with long latency periods. Aflatoxins also are associated with exacerbation of the protein malnutrition syndrome Kwashiorkor in human children (Ramjee et al., 1992). Estimating the human health effects of aflatoxins in terms of primary liver cancer, requires data on human exposure to aflatoxins. In developing countries, many individuals are not only malnourished but also are exposed chronically to high levels of this mycotoxin in their diet (Cardwell, 2001). The health risks decrease labor productivity, while increasing health costs and overall income losses due to opportunity costs linked to lost days of work (Lubulwa and Davis, 1994). Aflatoxins also are amongst the most potent mutagenic...

Procedure for setting regulatory limits for contaminants in food Regulatory limits

The scientific risk assessment is an assessment of the risks related to the presence of a contaminant in foodstuffs for human health and is the basis for any and all measures to be taken. If the contaminant is not a genotoxic carcinogen, then a health-based guidance value is derived. Human exposure (average and 95th percentile) is assessed in relation to this health-based guidance value. Particular attention is paid to vulnerable groups within the population and to high-level consumers. The exposure assessment also identifies the foods food groups that contribute significantly to exposure. The occurrence data are obtained for these foods and food groups following the application of good practices and used to determine the appropriate maximum level to be set for the protection of consumer health. Maximum levels are set at a strict level that is reasonably achievable when good agricultural, fishery and manufacturing practices are followed and that takes into account the risk related to...

Exposure to Dusts Inorganic Dusts

In general, inorganic dusts do not contribute to agricultural respiratory disease to the same degree as organic dusts. However, occupational exposures to mineral particles from inorganic dusts and crystalline silica may stimulate release of reactive oxygen species (ROS) in the lung. Reactive oxygen species may play a key role in the mechanisms of disease initiation and progression subsequent to inhalational exposures to these particles. In fact, multiple pathways may be facilitated to produce ROS, which may lead to inflammation, resulting in production of diseases such as pneumoconiosis and carcinogen-esis (31).

Types of studies considered appropriate for biologicals

As is the case with all studies conducted with biologicals, these studies should be conducted in pharmacologically relevant models. As discussed previously, the route and frequency of administration should be appropriate for the intended clinical use. Generally speaking, the duration of treatment used for toxicology studies conducted with biologicals should be at least equal to the intended duration of treatment, with ICH S6 identifying six months as being generally appropriate for chronic indications such as psoriasis and rheumatoid arthritis. However, the ultimate duration of treatment used for each product is influenced by a number of factors, including clinical indication, toxicity profile of the product, and immunogenicity.18 In the case of serious, life-threatening diseases, such as cancer, patients can be treated for durations exceeding that used in toxicology studies, assuming that the clinical trials are designed to adequately monitor for adverse events. 6.3.8 Carcinogenicity...

Antineoplastic Medications

Antineoplastic medications such as mitotane (Lysodren), chlorambucil (Leukeran), and azathioprine (Imuran) are usually teratogenic but can also be mutagenic, carcinogenic, and abortigenic. The principle governing working with cytotoxics is to keep exposure as low as possible. This may necessitate premix syringes and bottles prepared at a pharmacy under special mixing hoods, personal protective equipment, and isolation procedures. The clients and other people close to the patient are also potentially at risk and should be told of this and informed about drug administration and the disposal of feces, vomit, urine, saliva, and blood that may contain the active pharmaceutical. The prescription and or administration of cytotoxic drugs, including those that are used as immunosuppressive agents in veterinary medicine, should be restricted to specialist veterinarians who have adequate knowledge and appropriate facilities to work with these agents (33,34).

Deepak Bhatnagar Kanniah Rajasekaran Jeffrey W Cary Robert Brown Jiujiang Yu and Thomas E Cleveland

Aflatoxins are extremely carcinogenic secondary metabolites produced by Aspergillus fla-vus when this fungus invades crops such as maize, cotton, tree nuts and peanuts. Adverse health effects from the ingestion of these toxins have caused regulatory agencies throughout the world to limit the amount of aflatoxins that are permitted in food or feed that is available for sale. This results in undue economic burden on the grower. New biotechnologies such as (i) the use of disarmed, non-toxigenic biocompetitive strains of A. flavus in biocontrol of aflatoxin contamination, and (ii) identification of plant constituents that disrupt aflatoxin biosynthesis or fungal growth and their use in new biochemical marker-based breeding strategies to enhance resistance in crops to aflatoxin, could potentially save the agricultural industry in the United States alone hundreds of millions of dollars. In addition to the above mentioned studies, USDA, Agricultural Research Service scientists and other...

Neurotoxicity of Organochlorine Compounds

Patients with long-term occupational exposure to organochlorine pesticides may develop a variety of nonspecific complaints including headaches, nausea, fatigue, muscle twitching, and visual disturbances. There is no reliable statistical data associating exposure to organochlorines with any specific type or location of cancer. Some of the less obvious signs of cumulative tox-icity of these chemicals include paresthesias of the face, auditory or visual hallucinations, and perceptual disturbances, although the latter are more reliably associated with acute toxicity (41-44).

Pascal Fandohan Kerstin Hell and Walter F O Marasas

Mycotoxins are noxious secondary metabolites produced by fungi that are found in food products worldwide. In Africa, mycotoxins, particularly aflatoxins and fumonisins, are receiving increasing attention because of their impact on human health and international trade. Contamination of food commodities by these toxins results in reduction in quality and market value, with significant economic losses for farmers and food processors, and serious health implications for consumers (Cardwell and Miller, 1996). As much as 40 of the human productivity lost to diseases in developing countries may be due to diseases exacerbated by aflatoxin contamination (Miller, 1996). Aflatoxicosis outbreaks occurred in Kenya in 2004 causing 125 deaths (Azziz-Baumgartner et al, 2005 Okioma, Chapter 11), and reoccurred in 2005. Fumonisins have been associated with esophageal cancer in South Africa (Rheeder et al, 1992) and in China (Chu and Li, 1994). An outbreak of abdominal pain and diarrhea has been...

Occurrence and Toxicology

Aflatoxins are toxic and carcinogenic secondary metabolites produced primarily by Aspergillus flavus and A. parasiticus as well as A. nomius. One isolate of each of A. tamarii (Goto et al. 1996) and A. ochraceoroseus (Frisvad and Samson 1999) have been reported to produce aflatoxins (Klich et al. 2000). The aflatoxins consist of a group of at least 16 structurally related toxins (Goldblatt 1969) characterized so far. Amongst these, aflatoxins, B1, B2, G1 and G2 (AFB1, AFB2, AFG1 and AFG2) are the major toxins. Aflatoxins are polyketide-derived, bis-furan-containing dihydrofuranofuran and tetra-hydrofuran moieties (rings) fused with a substituted coumarin (Figure 1). A. flavus produces aflatoxins, B1 and B2 while A. parasiticus produces the four major aflatoxins, B1, B2, G1 and G2. The aflatoxins, M1 and M2, are modified forms of aflatoxin B1 found in bovine milk. Aflatoxin B1 (AFB1) is the most potent naturally occurring toxin and carcinogen known (Squire 1989). The toxicity of the...

Mycotoxin research sponsored by the Sorghum Millet CRSP

Aflatoxin and fumonisin hazards are associated with cancer, liver disease, immune suppression, retarded growth and development, nutritional interference, acute toxicity, neural tube defects, and death depending on the amount of toxin exposure and its duration. The symptoms depend upon the level of the toxin in the grain and the length of the exposure. The general perception is that sorghum is a safer grain to consume than is maize because the fungi that produce these toxins are rarer on sorghum and more common on maize (Leslie and Marasas, 2002 Leslie et al., 2005). INTSORMIL has worked with the International Institute of Tropical Agriculture (IITA) and the PROMEC unit of the Medical Research Council (MRC) in South Africa to test the hypothesis that the relative mycotoxigenicity of maize and sorghum grain differ.

Decolorization Of Dyes By Microorganisms

Azo linkages and aromatic sulfo groups do not occur naturally and they resist oxidative degradation. Partial degradation has been observed for anthraquinone and azo dyes during aerobic activated sludge treatment, but substantial removal of color from the wastewater was attributed to adsorption of the intact dye onto the sludge (Athanasopoulos 1991). The dyestuffs are generally more susceptible to anaerobic sludge degradation. The anaerobic reduction of azo dyes to colorless products by bacteria has been reported (Meyer 1981). The initial step in this transformation is the reductive fission of the azo group, resulting in the formation and accumulation of toxic and possibly carcinogenic aromatic amines. The rapid decolorization of a number of textile dyes and effluents by an immobilized anaerobic consortium had also been demonstrated (Nigam et al. 1996 Oxspring et al. 1996).

Method 57b Determination of easily oxidizable organic C by Tinsleys wet combustion

The addition of concentrated sulphuric acid on sodium (or potassium) dichromate is to produce chromium trioxide, which is a powerful oxidizing agent capable of oxidizing carbon to carbon dioxide. The solution is loosely called chromic acid, but although true chromic acid H2CrO4 has not been isolated, the aqueous solution contains dichromic acid, H2Cr2O7. The acid-dichromate reagent (hexavalent chromium) is corrosive to skin, respiratory and gastrointestinal tract, and may create a cancer risk. There may be restrictions on disposal into municipal sewerage systems, therefore storage for

Kerstin Hell Pascal Fandohan Ranajit Bandyopadhyay Sebastian Kiewnick Richard Sikora and Peter J Cotty

Aspergillus flavus, Aspergillus parasiticus and, rarely, Aspergillus nomius produce af-latoxins as secondary metabolites in agricultural products prone to fungal infection. Afla-toxins may cause liver cancer, suppressed immune systems, and retarded growth and development by contributing to malnutrition. Children are the most sensitive to the effects of af-latoxin-contaminated food. The effects of chronic exposure to aflatoxin are common in Africa, but acute toxicity, leading to death of humans, also has been reported (Azziz- The toxic effects of mycotoxins may be limited by natural or synthetic agents such as antioxidants, e.g., selenium, vitamins and provitamins, food components, e.g., phenolic compounds, coumarin, chlorophyll and its derivatives, fructose and aspartame, medicinal herbs and plant extracts, and mineral and biological binding agents, e.g., hydrated sodium calcium aluminosilicate, bentonites, zeolites, activated carbons, bacteria, and yeast (Farombi, 2006)...

Acute and chronic effects of herbicides on human health

Although much remains to be learned about the acute and chronic health impacts of herbicide use, public health reports and epidemiological studies indicate that certain herbicides can be responsible for direct, unintentional poisoning and may be associated with increased incidence of cancer and other disorders. Farmers, farm families, and agricultural workers are exposed to herbicides at higher concentrations than the general public and consequently may be subjected to greater health risks. Health issues relating to exposure to herbicides and other pesticides are particularly important in developing countries, where safe use is difficult because of unavailable or prohibitively expensive protective equipment, inadequate and poorly enforced safety standards, poor labeling, illiteracy, and insufficient knowledge of hazards by handlers and applicators (Pimentel et al., 1992 Repetto & Baliga, 1996, pp. 9-16). Chronic health effects of chemical exposure can include cancer and disorders...

The Safety of Microbial Enzymes Used in Food Processing

We know a great deal about the chemical nature of microbial toxins and their physiological affects on humans and animal models. Microbial foodborne toxins range in size from relatively large-molecular-weight toxic proteins produced by toxigenic bacteria to small-molecular-weight toxic organic compounds produced by toxigenic molds, algae and (rarely) certain bacterial species. These toxins induce a range of toxin-specific adverse effects that include vomiting and diarrhea (e.g., staphylococcal enterotoxins), paralysis and death (e.g., botulinal neurotoxins), and acute hepatic necrosis and cirrhosis and ultimately hepatocarcinoma (e.g., aflatoxin produced by toxigenic species of the mold genus Aspergillus). Notably, all of these foodborne toxins induce acute toxic effects that are evident within a few hours to a few days after exposure. In some cases chronic toxicity may also occur (e.g., long-term paralysis from exposure to a botulinal neurotoxin or liver cancer from aflatoxin...

Mycotoxins Mycotoxicosis and Mycotoxicology

Mycotoxin is a convenient generic term describing the toxic secondary metabolites produced by fungi. Myco means fungal (mold) and toxin represents poison. They encompass a considerable variety of low molecular weight compounds with diverse chemical structures and biological activities. Some mycotoxins could also be toxic to plants or other microorganisms but these compounds are not classified as antibiotics of fungal origin. Like most microbial secondary metabolites, the benefit of mycotoxins for the fungi themselves is still not clearly defined. In considering the effects of mycotoxins on animals, it is important to distinguish between mycotoxicosis and mycosis. Myco-toxicosis is used to describe the action of mycotoxin(s) and is frequently mediated through a number of organs, notably the liver, kidney, lungs, and the nervous, endocrine, and immune systems. On the other hand, mycosis refers to a generalized invasion of living tissue(s) by growing fungi (CAST 2003 Chu 1998). Due to...

Peter J Cotty Claudia Probst and Ramon Jaime Garcia

Aflatoxins are a group of highly toxic, cancer-causing chemicals produced by several members of the fungal genus Aspergillus. The presence of these mycotoxins in human foods can cause acute and chronic health effects (aflatoxicoses) including immune-system suppression, growth retardation, cancer, and death (Wild and Turner, 2002 Gong et al., 2004 Williams et al., 2004 Azziz-Baumgartner et al., 2005). Aflatoxins are carcinogens and genotoxins that directly influence the structure of DNA (Williams et al., 2004) and, as a result, occurrence of aflatoxins in human foods is strictly regulated to very low concentrations in developed countries. Indeed, in developed countries the exposure of domestic animals, even pets, is of both regulatory and economic concern. Deaths of pets due to aflatoxins in U.S. pet foods has had international economic impact in terms of both trade and litigation (Anonymous, 2006). Thus, in developed countries, the drive to abate aflatoxin contamination is due to loss...

Commercial Applications of Agricultural Biotechnology

The greater specificity in the handling of genes since the 1970s has meant that inventors could protect their discoveries by means of patents and other forms of intellectual property rights (IPR). This has led to an explosion of private investment in the biosciences, leading to what has been called a biotechnology revolution. Most modern biotechnology applications are in health care, where they offer new hope to patients with AIDS, genetically inherited diseases, diabetes, influenza and some forms of cancer. Biotechnology-based processes are now used routinely in the production of most new medicines, diagnostic tools and medical therapies. The global market for these products is approximately US 13 billion. benefits accruing to consumers in terms of maintaining food production at low prices. Health benefits for consumers are also emerging from new varieties of maize and rape-seed with modified oil content and reduced levels of potentially carcinogenic mycotoxins. The broader benefits...

Electromagnetic Energy

X-rays and gamma rays have extremely high frequency and energy content. As a result, this radiation can strike molecules in the body, knocking away electrons and leaving a damaged, electrically charged (i.e., ionized) remnant. Ionized molecules raise the risk of subsequent mutations and cancer. Accordingly, such high-frequency radiation is termed ionizing radiation and has been associated with increased cancer risk. Lower frequency radiation, such as radio waves, visible light, and microwaves, does not cause ionization, and is termed nonionizing radiation. Damage from nonionizing radiation is usually due to simple heating of tissues.

Economic impacts of aflatoxin

Four potential impacts of aflatoxin have been identified (Lubulwa and Davis, 1994) (i) deterioration of the food and nutritional quality of agricultural products with an accompanying reduction in sensory characteristics, e.g., taste, odor, texture and color, (ii) health-related productivity losses due to mutagenic and carcinogenic effects on humans who consume aflatoxin-contaminated food over an extended period of time, (iii) loss of income from livestock resulting from feeding aflatoxin-contaminated feedstuffs, e.g., higher mortality rates and lower feed to weight conversion ratios for chickens, ducks, egg-layers, and pigs, and (iv) losses of export markets and related economic gains due to regulations that restrict international trade of aflatoxin-contaminated grain. Aflatoxin contamination in agricultural commodities can result in considerable microeconomic losses, e.g., at the farm, household and community levels, as well as macro-economic losses, e.g. at the country or regional...

Other Health Effects of Mycotoxins

Little is known about the prolonged human effects of exposure to mycotoxins. One reason so little research has been done on its association with chronic disease is the difficulty and expense. Airborne exposure levels at coffee, cocoa bean, and spice processing plants resulted in increased blood levels of ochratoxin A, a secondary metabolite of Aspergillis and Penicillium (also common in grains and vine fruit), which has been found carcinogenic, genotoxic, teratogenic, immunotoxic and nephrotoxic in animals. The nephrotoxin affect has been shown in agricultural workers and rural residents in several Eastern European countries, and the rare urothelial tumor is 50 to 100 times more likely to occur in these countries (23-26). Linseed and peanuts are associated with A. flavus and its aflatoxin B1, which is associated with lung cancers among some workers and liver cancer in others. Pregnant women working with grain production have a twofold increased risk of preterm births or late abortions...

Other Selected Mycotoxins

Sterigmatocystin (ST) is a naturally occurring hepatotoxic and carcinogenic mycotoxin produced by fungi in the genera Aspergillus, Bipolaris, and Chaetomium as well as P. luteum see Bhatnagar et al. (2002) . Structurally related to AFB1 (Figure 5), ST is known to be a precursor of AFB1 (Bhatnagar et al. 2003). Although the carcinogenicity of ST is less (10-100 times) than that of AFB1 in test animals (van der Watt 1977), ST is a mutagen and genotoxin and has been found in cereal grains (barley, rice, and corn), coffee beans, and cheese (Chu 2002). A. terreus and several other fungi (e.g., A. flavus and A. fumigatus and some Penicillia) have been found to produce the tremorgenic toxins, territrems, aflatrem, and fumitremorgin. These mycotoxins contain both the indole ring of tryptophan and a dioxopiperazine ring formed by condensation of two amino acids. A. terreus, A. fumigatus, and Trichoderma viride also produce gliotoxin, an epipolythiopiperazines -3,6-diones-sulfur containing...

Importance of mycotoxins to economies and health

When there are no investments to assure that foods are not contaminated by mycotox-ins, a different importance of these toxins is evident but seldom recognized. In this regard the range of toxicities that may occur must be considered. Exposure to many of these myco-toxins has carcinogenic and teratogenic consequences, so the consequences of exposure need not be immediately connected with exposure and often are not considered because they are deferred or attributed to more obvious causal agents. For example, many mycotoxins have significant immune suppressing capabilities, but mycotoxins are only rarely connected with their impacts on disease epidemiology. As the toxins exert their effects through immunity and nutrition the problems they cause often are missed since current medical training and philosophy focus on responding to symptoms and curing diseases rather than preventing occurrence. Consequences similar to those observed for animal production on farms are observed in human...

Screening of Potential Leads from Diverse Microbial Sources

Recently, two structurally related compounds isolated from rare actinomycetes were found to have potent antifungal activity against plant pathogenic fungi. Daunomycin and spartamycins were isolated from Actinomadura roseola and Micromonospora spartanea, respectively (Kim et al. 2000b Nair et al. 1992). Both compounds have similar anthracycline aglycone moiety attached to one or three glycosides (Figure 2). Daunomycin noted for anticancer activity showed substantial in vitro antimicrobial activity against P. capsici, R. solani, B. cinerea, Cladosporium cucumerinum, Cylindrocarpon destructans, D. bryoniae, S. cerevisiae, and Gram positive bacteria. In particular, daunomycin showed strong inhibitory effect on the mycelial growth of P. capsici and Phytophthora development on pepper plants. In vivo efficiency against Phytophthora infection in pepper plants was somewhat less effective than that of the commercial fungicide metalaxyl.

Richard T Awuah Kwaku O Agyemang Simon C Fialor and Curtis M Jolly

In 1998, a news item with the sensational banner headline, Shocking Scientific Report Kenkey Causes Cancer appeared in the August 17-18 edition of the Ghanaian Chronicle, a Ghanaian newspaper. The author of the article, who at the time also was the editor of the newspaper wrote, Scientific studies from major processing sites and markets in Accra have concluded comprehensively that there is widespread occurrence of the strain (italics mine) that causes cancer, particularly liver cancer in Ga kenkey (Koomson, 1998a). The writer based his report on a publication by Kpodo et al. (1996), that documented the occurrence of mycotoxins in fermented maize products. Koomson (1998a) showed some lack of understanding of the matter when, for example, he wrote According to the report, maize which is a major dietary staple has been identified as the 'villain'. The molds which develop on the maize particles, because of delayed or poor drying process, contain a bacteria called aflatoxin (italics mine),...

General Epidemiological Liver and Kidney Findings in Farmers

Cohort studies in farmers or agricultural workers have mostly been targeted at cancer outcomes those focused on other health issues are scarce. The overall findings suggest that farmers and farm residents experience less cancer and more favorable mortality patterns, except from accidents, than their respective control groups. Liver cirrhosis as a cause of death was significantly less than expected in New York farmers, and so was the incidence of liver and kidney cancer in several cohorts of farmers, agricultural workers, and licensed pesticides applicators in other studies (3-7). One cohort study among farmers and agricultural workers from Italy found a small excess of kidney cancers based on five observations against the background of overall reduced cancer mortality. Studies in female farm residents have shown either insignificant elevations of liver cancer risk or no elevations at all, with kidney cancer risk being significantly reduced. In a large case-control study of...

Maximum levels for aflatoxins

Aflatoxins are mycotoxins produced by certain species of Aspergillus, usually at high temperatures and humidity levels. Aflatoxins may be present in a large number of foods, e.g., nuts, groundnuts, dried fruit, cereals (especially maize) and spices. The European Scientific Committee for Food expressed in its opinion of 23 September 1994 (12) that aflatoxins are geno-toxic carcinogens. For such substances there is no threshold below which no harmful effect is observed, and, therefore, no tolerable daily intake can be set. Current scientific and technical knowledge and improvements in production and storage techniques do not suffice to prevent aflatoxin biosynthesis and it is not technically possible to completely eliminate aflatoxins in food. Thus, the maximum levels are set as low as reasonably achievable (ALARA) (Table 1). The aflatoxin group is a series of related compounds with varying toxicity, incidence and levels in food. Aflatoxin B1 is the most toxic member of the aflatoxin...

Mycotoxin Biosynthetic Genes As Targets for Detection of Fungi

Mycotoxins are a chemically diverse group of fungal secondary metabolites that are harmful to animals and humans. Several hundreds of different mycotoxins have been identified, but only about 20 of them are relevant to human health. Most of the mycotoxin-producing species are filamentous ascomycetes or deuteromycetes, Aspergillus, Fusarium and Penicillium are considered as being the most important mycotoxin-producing genera. Most mycotoxins are very resistant to physical or chemical treatments. Although well-documented cases of mycotoxicoses are rare, the constant uptake of small amounts of mycotoxins, especially those with carcinogenic activity, can have profound effects on human health. Apart from the use of specific rDNA gene-based or RAPD-based probes, mycotoxin biosynthetic genes can serve as ideal targets for the detection of the producing fungi. To date, a number of biosynthetic genes of mycotoxins have been isolated and characterized. These gene sequences could serve as...

Immunogenicity of biological products

The route of administration is a particularly important factor that influences the immunogenic potential of biological therapeutics. As stated previously, most biological drug products are administered parentally, and the subcutaneous route is usually more immunogenic than intravenous or intramuscular administration.72,76-79 Underlying disease, concomitant medication, and the immune status of patients can also affect antibody responses to administered protein drugs. For example, cancer patients administered chemotherapeutic agents that cause myelosuppression may have a compromised immune system, and thus are less likely to mount an immune response to a biological therapeutic.64 Although these are some general considerations, immunogenicity can occur with any protein, even in conditions listed above where immunogenicity is less likely (i.e., single intravenous dose).

Historical Background

Outbreaks of toxicoses associated with the ingestion of moldy foods and feeds by humans and animals have also been recorded in last century. Deaths of livestock were reported earlier from consumption of moldy corn in feed of horses in Illinois, Russia and swine in Southeastern United States (Christiansen and Kauffman 1969) in the 1930s. A well-documented example is the disease called alimentary toxic aleukia (ATA) that resulted in more than 5000 deaths in humans in the Orenberg district of the USSR during World War II, and the cause of later was found to be trichothecene mycotoxins. Modern myco-toxicology was not developed until the discovery of aflatoxins in the early 1960s as the causative agent in the peanut meal causing the Turkey X disease that killed more than 10,000 turkeys fed with the contaminated meal. Because aflatoxins are a series of highly potent carcinogens produced by commonly occurring Aspergillus flavus and A. parasiticus, research has focused new attention on...

Martin Gilmour and Marianne Lindblom on behalf of the Working Group on Ochratoxin A in cocoa

Ochratoxin A, sometimes abbreviated as OTA, is a secondary metabolite produced by some Aspergillus and Penicillium spp. Ochratoxin A is found in a range of foods such as cereals, dried fruits, grape juice, coffee, cocoa, wine and beer with cereals providing the largest contribution to the intake of ochratoxin A in Europe (DG Health and Consumer Protection, 2002). Ochratoxin A's toxicological effects have been evaluated on several occasions by the Joint FAO WHO Expert Committee on Food Additives (JECFA) and the EU Scientific Committee for Foods (SCF) (DG Health and Consumer Protection, 1998 JECFA, 2001). SCF concluded in 1998 that ochratoxin A possesses carcinogenic, nephrotoxic, teratogenic, immunotoxic and possibly neurotoxic properties. Based on this evaluation SCF recommended that ochratoxin A exposure should be reduced as much as possible ensuring that exposures are < 5 ng kg bw per day (DG Health and Consumer Protection, 1998). Since 1998 further research, especially on the...

Occurrence and toxicity of aflatoxins

Aflatoxins are potent carcinogens and mutagens. Naturally occurring mixtures of afla-toxins are classified as Class 1 human carcinogens (IARC, 1993). There is a correlation between the incidence of liver cancer in humans in some areas of Africa and dietary exposure to aflatoxins. Studies in Kenya, Mozambique, Swaziland, and South Africa have found that aflatoxin levels in the diet and the incidence of primary liver cancer are correlated (Groopman et al, 1988). Aflatoxin consumption also has been implicated in some infant diseases such as kwashiorkor, a form of protein malnutrition (Hendrickse, 1984), and protein-deficient diets may increase aflatoxin toxicity (Hendrickse et al., 1982).

Aflatoxin management in peanut

Aflatoxins Bi and Gi are the most commonly produced forms in peanut. These toxins are involved in several human diseases, particularly liver cancer and growth defects in children. Aflatoxin interactions with Hepatitis B and C viruses result in relatively high levels of primary hepatocellular carcinoma. Aflatoxins also are toxic to livestock, including ruminants, poultry, birds and fish, when contaminated meal is used in their feed. Due to its human and livestock health implications, aflatoxin contamination has become a major issue in the international trade of peanuts and can directly impact the lives of poor farmers by reducing their income.

Brief History of Food Safety and Agriculture

Since 1962, the Codex Alimentarius Commission (CAC) of the Food and Agricultural Organization of WHO has been responsible for developing standards, guidelines, and other recommendations on the quality and safety of food to protect the health of consumers and to ensure fair practices in food trade. In the United States, various regulations exist to enhance food safety. Early actions of the U.S. Department of Agriculture (USDA) culminated in the passage of the 1906 Food and Drug Act that helped increase food safety for the public. In 1910, the Insecticide Act established product-labeling provisions. The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) of 1947 required registration of pesticide products with the USDA prior to domestic or foreign sales. The Federal Food, Drug, and Cosmetics Act that evolved from the 1906 statute was expanded in 1954 by the Miller Amendment that established pesticide tolerances in or on agricultural commodities based primarily on good...

Case Studies in Biopiracy Pharms and Farmers

Grace's encounter with India's neem tree reflects some elements of the biopiracy paradigm (see National Research Council, 1992). Almost as notorious is the story of Eli Lilly & Co.'s derivation of vinblastine and vincristine, two cancer-fighting alkaloids, from the rosy periwinkle (see, e.g. Hunter, 1999, p. 130). Vinblastine is used in treating Hodgkin's disease (see Little, 1998) vincristine has become the drug of choice for treating childhood leukemia (see Veerman, 1996). The commercialization of products derived from neem and the rosy periwinkle has sparked controversies over alleged acts of biopiracy.

Nomenclature and historical perspective

The first good written account of the species is provided by Herbst (1792), who gave a good description and an illustration (as Figure 1 of his Plate 28) under the incorrect name Cancer (Astacus)carcinus Linnaeus, 1758. Linnaeus' Cancer carcinus, however, is an American species of Macrobrachium, which Herbst (1792) also described and illustrated (as Figure 2 of his Plate 27) but as a new species under the name Cancer (Astacus) jamaicensis. Herbst's descriptions and illustrations so clearly characterised the two species that his nomenclature was adopted by most subsequent authors and, during the following 150 years, the specific name carcinus was generally used for the present East Indian species and that of jamaicensis for the American one. In the meanwhile, J.G. De Man (1879) found a new species from New Guinea which he named Palaemon rosen-bergii. The first person who challenged Herbst's nomenclature was Sunier (1925), who showed that Linnaeus' description of Cancer carcinus was...

Food Safety Assessment For Use Of bsT

Its link to cancer and birth defects, was used illegally in Europe for veal production. Very high levels of DES were used and some of the contaminated veal was processed into baby food consumed in Europe. This illegal use raised considerable safety concerns, leading to the total ban of all steroid growth promotants used in beef cattle production. The ban in Europe remains in effect to this day despite aforementioned scientific reviews carried out by regulatory scientists both in Europe and the United States that continue to confirm the safe use of approved growth promotants such as estrogen in beef cattle production.36 The total ban in Europe on the use of growth promotants in beef cattle occurred around the same time the safety of bST was being reviewed by European regulatory scientists Joint FAO WHO Expert Committee on Food Additives (JECFA) . The public did not differentiate between protein and steroid hormone use in food production, which made the safety of bST an issue in Europe.

MuocENic Activity of IGF1

The epithelium of the intestine, with a high density in the colon,136 and the incidence of colorectal cancer is increased in acromegalic patients who have pituitary tumors that secrete excessively high concentrations of free IGF-1 in their plasma,137 concern has been expressed that increased concentrations of milkborne IGF-1 may increase the risk of colon cancer.39 After considering all of these factors, and in recognition of the minimal impact of milk IGF-1 on endogenous levels in the body, the JECFA review concluded I t was extremely unlikely that IGF-1 residues cause any systemic or local mitogenic reaction.39 Following the JECFA review in 1998,39 a few studies appeared in the literature associating higher circulating levels of IGF-1 with increased risk of development of breast, ovarian, and prostate cancer.141-144 Based on these publications, a Citizen Petition was filed with the FDA suggesting that there was a connection between IGF-1 and cancer, and that bST use could therefore...

Abebe Menkir Robert L Brown Ranajit Bandyopadhyay Zhiyuan Chen and Thomas E Cleveland

Contamination with aflatoxins and fumonisins occur in warm, humid, tropical and subtropical maize-growing environments that are conducive to growth and development of the two fungi (Widstrom, 1996 Kpodo and Bankole, Chapter 9 Siame and Nawa Chapter 10). Maize contaminated with mycotoxins is a serious problem in Sub-Saharan Africa because most of the maize grain in many countries is used for human consumption and the capacity to monitor the mycotoxin levels in the grain is limited (Widstrom, 1996). The widespread exposure to aflatoxin in Africa has been implicated in the increased incidence of acute toxicosis, liver cancer, and morbidity in children suffering from kwashiorkor (Miller, 1996 Widstrom, 1996 Gong et al., Chapter 6). The consumption of fumonisin-contaminated maize foods also has been associated with outbreaks of esophageal cancer (Rheeder et al., 1992 Thiel et al., 1992) and neural tube birth defects in humans (Stack, 1998). Some reports suggest that various processing...

Avoiding Human Exposure

Example, the carcinogenic effect of AFB1 is affected by nutritional factors, dietary additives, and anticarcinogenic substances. Diet containing chemoprotective agents and antioxidants such as ascorbic acid, BHA, BHT, ethoxyquin, oltipraz, penta-acetyl geniposide, Kolaviron biflavonoids, and even green tea, have also been found to inhibit carcinogenesis caused by AFB1 in test animals. The toxic effect of OA and FmB to test animals was minimized when antioxidants such as vitamins C and E are added to the diet. Ascorbic acid also provided protective effect against AFs. Aspartame, which is partially effective in decreasing the nephrotoxic and genotoxic effects of OA, competes with OA for binding to serum albumin. L-phenylalanine was found to have some protective effect for the toxic effects of OA because it diminishing OA's inhibitory effect to some of enzymes discussed earlier.


Over a 20-year period of research in West Africa we have demonstrated, by using biomark-ers, the ubiquitous nature of high level exposure to aflatoxins throughout life. One cannot help but speculate as to what the reaction would be if continued exposure to high levels of a potent carcinogen was to be left unaddressed in Europe or North America. Indeed it is ironic that aflatoxins have evoked the most interest recently in the context of the slim risk of their use as chemical weapons by the late Saddam Hussein or the relatively limited numbers of acute aflatoxicosis outbreaks, such as that in Kenya, rather than in terms of the major public health problems of hepatocellular carcinoma and, potentially, of child morbidity and mortality (Table 3). The scale of the former consequences of aflatoxin exposure is dwarfed by the impact of these toxins if they truly impair growth and immunity in children and thereby make a significant contribution towards the 4.5 million deaths annually of...

Risk assessment

The techniques for assessing the potential for allergenicity, toxicity and carcinogens in food are well established and should be readily able to be used by trained professionals in many countries (Metcalf et al., 1996 Lehrer, 2000). Given increasing global concerns about food safety, all countries will need to have in place food-safety regulations and the human and institutional capacity to be able to ensure the safety of their food supply (World Bank, 2000).

Abused Drugs

Several substances, such as the opiates and methamphetamines, have medical uses so that any drug testing program must allow for a review to determine if the substance is being taken legally. Some substances, such as PCP, once had a legal use in the United States and are still used in some countries. Legality of the substances varies by country for example, heroin, illegal in the United States, is used as an analgesic in treatment of cancer in Great Britain and other countries (8,9).


Aflatoxins are produced by species of Aspergillus flavus and Aspergillus parasiticus in various commodities including maize, rice, barley, wheat, sorghum, peanuts and copra. Asper-gillus flavus produces only aflatoxins B1 and B2 whereas A. parasiticus produces aflatoxins Bi, B2, Gi and G2. The toxicological effects of aflatoxins are dose-dependent. At high doses they are lethal if consumed, causing liver, myocardial and kidney tissue damage. At sub-lethal doses aflatoxins cause chronic toxicity, e.g. liver cirrhosis, and at low-level exposure, they are potent human hepatocellular carcinogens (Wild and Turner, 2002). Aflatoxins also are mutagenic and teratogenic and can depress cell-mediated immunity (Williams et al., 2004). Recently these toxins have been implicated in the stunting of children in Benin and Togo, where growth was reduced in children eating foods highly contaminated with aflatoxins introduced at weaning (Gong et al., 2002). Aflatoxin B1 acts synergistically with...


Peripheral nervous system much earlier than in any other organ system. This explains why, except in cases of deliberate poisoning, as in suicide, manifest liver or kidney damage due to insecticide use hardly ever occurs in persons who handle them professionally. One exception to this statement may be lead arsenate, which was used as an insecticide in vineyards in the past and allegedly caused liver cirrhosis and liver cancer in wine growers. Such cases have been acknowledged as an occupational disease in Germany however, some doubted the relevance of arsenic as the major culprit. Elevated liver enzyme activities in professional pesticide sprayers have occasionally been reported, whereas others did not confirm these findings (19-25).

Public health status

Statistics generally attribute to the presently recognized risks of aflatoxins (liver cancer) a small fraction of the burden of disease, and on this basis aflatoxin is rated a lower priority for Ministries of Health in developing countries than are many other more pressing problems. Hopefully this position will change, as it is based on untenable assumptions about the levels of exposure and toxicities occurring in developing countries. Another factor that strongly influences the perception of aflatoxin is the presence of the hepatitis B virus, with which aflatoxin interacts synergistically. When these two agents are combined, the potency of aflatoxin as a carcinogen is increased 30 fold (Henry et al., 2002). This synergism means that institutions concerned for people with hepatitis B should perceive aflatoxin as a much more dangerous toxin than they currently do. Although there are campaigns to inoculate people against hepatitis B, there currently are 80 million people with the...


Fumonisin B1 is primarily a hepatotoxin and carcinogen in rats (Class 2B carcinogen). Feeding culture material from F. verticillioides or pure FmB1 to rats resulted in cirrhosis and hepatic nodules, adenofibrosis, hepatocellular carcinoma-ductular carcinoma, and cholangiocarcinoma (Gelderblom et al. 2001 Haschek et al. 2001). Kidney is also a target organ, and tubular nephrosis was found both in rats and in horses of field cases associated with equine leukoencephalomalacia (ELEM). In addition to FmB1, which was originally found to be a potent cancer-causing agent, FmB2 and FmB3 have also been found to be carcinogens and have cancer initiation and promoting activities in rats. The effective dose of FmB1 for cancer initiation in rat liver depends both on the levels and on the duration of exposure. In cell culture systems, FmB1 has been demonstrated to be mitogenic and cytotoxic, without genotoxic effects (Gelderblom et al. 2001). Kidney cells have also been shown to be targeted by these...


The European Commission legislation and Codex Alimentarius currently are evaluating ochratoxin A contamination of food commodities and raw material. Ochratoxin A can be found in cereals, wine, grape juice, dried vine fruits, coffee, spices, cocoa, and animal derived products, e.g., pork. The current European Commission legislation includes unprocessed cereals and cereal products, including baby food. JECFA (the Joint FAO WHO expert committee on Food Additives) evaluated ochratoxin A at its 56th meeting in 2001 (FAO WHO, 2001). They determined that ochratoxin A is nephrotoxic and causes renal cancer, but that the mechanism of action is not yet clear as both genotoxic and non-genotoxic mechanisms have been proposed.

Ionizing Radiation

Ionizing radiation is uncommon in agricultural settings. Ionizing radiation may be used in food sterilization and decontamination procedures. Excessive exposure to ionizing radiation may lead to acute or chronic radiation sickness. Rapidly dividing cells, such as the lining of the gastrointestinal tract and blood-generating cells in the bone marrow, are particularly sensitive to radiation exposure. Hence, acute radiation sickness is characterized by gastrointestinal disturbances, bleeding due to platelet loss, infections due to immune-system damage, and anemia. Exposed skin may suffer acute burns and subsequent scarification. Chronic radiation exposure may be associated with cancer and reproductive abnormalities. Prevention of illnesses and injuries from ionizing radiation involves eliminating or minimizing exposure. Radiation sources should be properly shielded and radiation exposures monitored. Persons not educated in working around such sources should not have access.

Reproductive Hazards

Fertility, gestation, and pregnancy outcome are dependent on complex biological processes beginning early in life. Disruption of these processes can happen with environmental exposures in utero and throughout childhood development, as well as in adulthood through occupational and environmental exposures. Interference with development or functioning of the reproductive tract in males and females can result in diminished fertility, infertility, adverse pregnancy outcomes, congenital malformations, and childhood cancer. Studies have documented associations between living or working in an agricultural area and adverse reproductive outcomes. Exposure to chemicals, mainly pesticides, has been linked to infertility and diminished fertility, spontaneous abortion, birth defects, and childhood cancer. A large number of studies suggest pesticide exposure is associated with these adverse reproductive outcomes, but few studies quantify the type of pesticide or measure exposure levels. Biomarkers...

Ochratoxin A

Ochratoxin A is the more toxic of the two derivatives and is nephrotoxic, immunosuppressive, carcinogenic and teratogenic in all experimental animals tested (WHO, 1990). It has been classified as a Group 2B compound, i.e., possibly carcinogenic to humans (IARC, 1987). The toxin has been associated with endemic nephropathy which is a fatal renal disease found among rural populations in Croatia, Bosnia, Herzegovina, Serbia, Bulgaria and Romania.


Acute and chronic phototoxic reactions may occur. The acute response is characterized by erythema and edema followed by hyperpigmentation and desquamation. The end point of chronic damage may be cutaneous cancer formation as a result of nucleic acid and cytoplasmic molecular injury. Treatment consists of removal of the offending agent and systemic steroids (31-33).

Cutaneous Neoplasms

Agricultural occupational skin cancers are malignancies that result from exposure to carcinogenic forces present in agriculture. Of all occupational cancers, 75 are skin cancers, and 60 of those are basal cell carcinomas (BCCs), 34 are squamous cell carcinomas (SCCs), and 6 are mixed. Actinic keratoses (AKs) are precancerous lesions caused by excessive sun exposure. Melanomas may occur but typically appear in older persons, and their exact rate in agriculture is unknown. In Finland, lip cancer (BCC and SCC) is extremely common but cancers of the head aren't, presumably due to wearing hats (Table 18.6) (1,8,9,37,41,42). Causes of Agricultural Skin Cancers Fair skin, blond hair, and blue eyes predispose to the appearance of skin cancers in Caucasian people. The elevated levels of melanin in dark-skinned people offer an incomplete protective effect. The most common types of cancer that affect the Caucasian population are BCC and SCC (43). There are five recognized causes of agricultural...

Types of aflatoxin

Hundreds of fungal species from > 12 fungal genera produce > 300 identified mycotoxins which can pose a threat to the health of at least some mammalian species. Of these myco-toxins, the aflatoxins are the greatest known concern because they are both highly toxic and potentially carcinogenic. Aflatoxin is a naturally occurring mycotoxin produced by three fungal species Aspergillus flavus, Aspergillus parasiticus and Aspergillus nominus, of which A. flavus is the most common. These fungi occur principally in soil and decaying vegetation. There are four main types of aflatoxin Bb B2, Gj, G2, and two additional minor ones, Mi and M2, usually associated with milk. Aflatoxin B1 is the most common member of this family of mycotoxins and has extremely high carcinogenic potency. All countries with mycotoxin regulations in 2003 have at least regulatory limits for aflatoxin B1 or for the sum of aflatoxins B1, B2, G1 and G2 in foods and or feeds (FAO, 2004). It is unlikely that commodities...

Food Safety Concerns

The potential risks of biotechnology on human health may include toxic reactions, increased cancer risks, food allergies, food contamination, and antibiotic resistance (Table 4.1). There is also concern that GMOs in animal feed might present a health risk for consumers, or for the animal itself. Consumers are also concerned about the long-term health effects of genetically modified foods. 2. Increased cancer risks. Monsanto's bovine somatotrophin (growth hormone) injected into dairy cows to produce more milk has been reported to cause cancer in human breast, prostate, and colon.


Fumonisins have been associated with a high incidence of esophageal cancer in certain areas of the Transkei region of the Eastern Cape Province in South Africa (van Rensburg, 1985 Rheeder et al, 1992) and high levels of fumonisin levels have been found in maize from this and other parts of the world known to have unusually high rates of esophageal cancer such as the Linxian county region in China (Yang, 1980), northeastern Iran (Kmet and Mahboubi, 1972 Shephard et al., 2000), northeastern Italy (Franceschi et al., 1990). Fumonisins also may be a risk factor in primary liver cancer and could act synergistically with aflatoxins, microcystins and or deoxynivalenol (Ueno et al., 1996). Whether fumonisin Bi is a carcinogen in human beings has not been established however, based on toxicological evidence, the International Agency for Research on Cancer (IARC) has designated fumonisin B1 to be possibly carcinogenic to humans (class 2B carcinogen) (IARC, 2002). The development of neural tube...