Effects Of Aflatoxin Exposure Research Articles

Effect of maternal aflatoxin exposure on growth and morbidity of infants 0 to 3 months

Aflatoxin exposure has been implicated in adverse human health outcomes in areas where the toxin is prevalent in foods [1]. Consequently, many people may be chronically exposed to large amounts of the toxin worldwide. The effect of aflatoxin exposure is felt more in developing countries and this may be attributed to high levels of malnutrition coupled with chronic exposure to high levels of the toxin in their diets [2]. Consumption of high levels of aflatoxins has been associated with aflatoxicosis resulting in death, while chronic dietary exposure to aflatoxins is associated with liver and other cancers and poor growth outcomes in young children [3]. Exposure of infants to aflatoxins may be detrimental to their normal growth and other aspects of health later in life. Early linear growth retardation is associated with poor cognitive development, reduced physical productivity, a greater risk of poor pregnancy outcomes later in life, including low birth weight babies and a greater risk of obesity, coronary heart disease, diabetes and hypertension later in life [3]. Therefore, protection of fetuses, infants and young children from the effects of aflatoxins through maternal exposure would not only reduce the risk of them not realizing their cognitive potential, but also contribute to reducing the risk of non-communicable diseases whose prevalence is on the rise, not just in developed countries, but also in developing countries.

Analysis of Aflatoxin Biomarkers in the Hair of Experimental Animals.

Analysis of body fluids and tissues of aflatoxin exposed individuals for the presence of aflatoxins and aflatoxin metabolites has emerged as a reliable indicator of exposure and metabolism of aflatoxins. However, current aflatoxin biomarkers are not appropriate for investigating the long-term effects of aflatoxin exposure. In this explorative study, we investigated the analysis of hair as a complementary or alternative matrix for the assessment of biomarkers of long-term aflatoxin exposure. Three groups of guinea pigs were orally dosed with 5 ugkg−1bw−1, 50 ugkg−1bw−1, and 100 ugkg−1bw−1 of AFB1. Urine and hair samples were collected on days 0, 1, 2, 3, 7, 30, 60, and 90 and analysed for AFB1 and AFM1 using UHPLC-MS/MS. AFB1 and AFM1 were detected in 75% and 13.6%, respectively, of the day 1 to day 7 urine samples. AFB1 was detected in hair samples collected from day 3 up to day 60. This is the first report to confirm the deposition of AFB1 in the hair of experimental animals. These findings indicate that hair analysis has the potential to provide an accurate long-term historical record of aflatoxin exposure with potentially important implications for the field of aflatoxin biomarkers.

The effects of aflatoxin exposure on Hepatitis B-vaccine induced immunity in Kenyan children

Globally, approximately three million children die each year from vaccine preventable infectious diseases mainly in developing countries. Despite the success of the expanded immunization program, not all infants and children around the world develop the same protective immune response to the same vaccine. A vaccine must induce a response over the basal immune response that may be driven by population-specific, environmental or socio-economic factors. Mycotoxins like aflatoxins are immune suppressants that are confirmed to interfere with both cell-mediated and acquired immunity. The mechanism of aflatoxin toxicity is through the binding of the bio-activated AFB1-8, 9-epoxide to cellular macromolecules. We studied Hepatitis B surface antibodies [anti-HBs] levels to explore the immune modulation effects of dietary exposure to aflatoxins in children aged between one and fourteen years in Kenya. Hepatitis B vaccine was introduced for routine administration for Kenyan infants in November 2001. To assess the effects of aflatoxin on immunogenicity of childhood vaccines Aflatoxin B1-lysine in blood serum samples were determined using High Performance Liquid Chromatography with Fluorescence detection while anti-HBs were measured using Bio-ELISA anti-HBs kit. The mean±SD of AFB1-lysine adducts in our study population was 45.38±87.03pg/mg of albumin while the geometric mean was 20.40pg/mg. The distribution of AFB1-lysine adducts was skewed to the right. Only 98/205 (47.8%) of the study population tested positive for Hepatitis B surface antibodies. From regression analysis, we noted that for every unit rise in serum aflatoxin level, anti-HBs dropped by 0.91mIU/ml (-0.9110038; 95% C.I -1.604948, -0.21706). Despite high coverage of routine immunization, less than half of the study population had developed immunity to HepB. Exposure to aflatoxin was high and weakly associated with low anti-HBs antibodies. These findings highlight a potentially significant role for environmental factors that may contribute to vaccine effectiveness warranting further research.

Aflatoxin B1 albumin adducts in plasma and aflatoxin M1 in urine are associated with plasma concentrations of vitamins A and E.

Although aflatoxin exposure has been associated with micronutrient deficiency in animals, there are few investigations on the effects of aflatoxin exposure on micronutrient metabolism in humans. To examine the relationship between aflatoxin B1 (AFB1) albumin adducts (AF-ALB) in plasma and the aflatoxin M1 (AFM1) metabolite in urine and plasma concentrations of retinol (vitamin A) and alpha-tocopherol (vitamin E) in Ghanaians. A cross-sectional study of 147 adult participants was conducted. Blood and urine samples were tested for aflatoxin and vitamins A and E levels. Multivariable analysis showed that participants with high AF-ALB (>or=0.80 pmol/mg albumin) had increased odds of having vitamin A deficiency compared to those with lower AF-ALB [Odds Ratio (OR)=2.61; CI=1.03-6.58; p=0.04]. Participants with high AF-ALB also showed increased odds of having vitamin E deficiency but this was not statistically significant (OR=2.4; CI=0.96-6.05; p=0.06). Conversely, those with higher AFM1 values had a statistically nonsignificant reduced odds of having vitamin A deficiency (OR=0.31; CI=0.09-1.02; p=0.05) and a statistically significant reduced odds of having vitamin E deficiency (OR=0.31; CI=0.10-0.97; p=0.04). Participants with high AF-ALB or high AFM1 (>or=437.95 pg/dL creatinine) were almost 6 times more likely to be hepatitis B virus surface antigen (HBsAg)-positive (OR=5.88; CI=1.71-20.14; p=0.005) and (OR=5.84; CI=1.15-29.54; p=0.03) respectively. These data indicate that aflatoxin may modify plasma micronutrient status. Thus, preventing aflatoxin exposure may reduce vitamin A and E deficiencies.

Abstract PL02-02: Foodborne toxins in developing countries

Abstract PL02-02 Mycotoxins are fungal metabolites which commonly contaminate the human food supply, particularly cereals (e.g. maize (corn), wheat, barley and oats), oilseeds (e.g. groundnuts (peanuts)) and tree nuts. Estimates are that around 25% of food worldwide contains these toxins. The mycotoxins of most importance from a human health perspective are aflatoxins, fumonisins, ochratoxin A, tricothecenes and zearalenone. Exposure to aflatoxins and fumonisins, both of which are carcinogenic, occurs predominantly in developing countries. This is due to a combination of factors, including the climatic conditions which promote crop stress, fungal growth and toxin production during cultivation and storage; the reliance on a few dietary staple foods; inadequate food sufficiency, translating to consumption of contaminated food; and the absence of regulation, or implementation of regulations, to control mycotoxin levels in the food supply. At the same time, understanding the human health effects of mycotoxins has been hampered, at least in part, by the absence of accurate exposure measurements. In response, biomarkers offer to improve exposure assessment at the individual level. These same biomarkers can be used to evaluate potential approaches to reduce mycotoxin exposure. Aflatoxins have been associated with increased liver cancer risk in interaction with chronic hepatitis B virus (HBV) infection, but the underlying molecular mechanisms remain ill-defined. Genetic polymorphisms in genes coding for aflatoxin metabolising enzymes and DNA repair enzymes were associated with an altered cancer risk1,2 and earlier data suggested that HBV infection could alter expression of some of these metabolising enzymes3. In West Africa there is a high prevalence and level of dietary exposure to aflatoxins, with >90% of the individuals having detectable blood aflatoxin-albumin adduct4. Exposure is life-long, beginning in utero, reducing during breastfeeding, but increasing markedly at weaning. This exposure early in life in West Africa has been associated with a striking impairment of growth in young children5-8. Exposure was also associated with a decrease in salivary IgA levels9. Growth and immune impairment could therefore be critical in pre-disposing children to the infections, including HBV, that result in the high morbidity and mortality in these populations. In parallel, to the studies of disease aetiology, we evaluated a simple post-harvest intervention in Guinea to reduce aflatoxin contamination of the groundnut crop. This involved sun-drying the crop on mats prior to storage; the use of natural fibre bags for storage; the use of wooden pallets to keep the bags off the moist earth in the storage facilities and the application of insecticide on the floor of the facility. This intervention resulted in a >50% mean reduction in aflatoxin-albumin adducts in subjects in the intervention villages five months post-harvest10. In addition, around 20% of subjects in the intervention villages had no detectable aflatoxin-albumin biomarker in their serum compared to less than 3% in the control villages. This demonstrates that relatively simple prevention approaches can make a significant impact on aflatoxin exposure when implemented at the small subsistence farm level. This primary prevention compares well with the alternative approach of chemoprevention using oltipraz, chlorophyllin, green tea or broccoli tea as demonstrated in studies in aflatoxin-exposed individuals in the People’s Republic of China11. More recently the use of absorbent clays in the diet in Ghana has been shown to reduce aflatoxin biomarker levels12. Overall the prevention of hepatocellular carcinoma in developing countries depends on reducing chronic infection with hepatitis B or C viruses as well as a reduction in aflatoxin exposure. It is also notable that the health effects of aflatoxin exposure may extend well-beyond liver cancer if the associations with impaired growth and immunity are causal. This would significantly change the priority assigned to tackling this environmental toxin. Fumonisins are predominantly found in maize. These toxins have been associated with squamous cell carcinoma of the oesophagus in parts of southern Africa and People’s Republic of China and, more recently, with a high incidence of neural tube defects on the Texas-Mexico border. We developed a urinary biomarker for fumonisin exposure and in a study in Mexico showed that tortilla intake, the major source of maize, was correlated with the biomarker13. In the former Transkei region of South Africa a high level of fumonisin exposure was also demonstrated using the urinary biomarker. The effectiveness in reducing fumonisin contamination by hand-washing and sorting maize kernels prior to cooking was evaluated using the biomarker in a study of subsistence farming families. In summary, mycotoxins are common in much of the food supply of the developing world. However, the adverse health effects of these chronic exposures are not fully understood. The ability to measure exposure permits both aetiologic and intervention studies to be conducted in the future. Finally, in assessing the benefits of interventions, the complex range of adverse health effects resulting from mycotoxin exposure needs to be taken into account. Citation Information: Cancer Prev Res 2008;1(7 Suppl):PL02-02.

Risk of Exposure to and Mitigation of Effect of Aflatoxin on Human Health: A West African Example

The purpose of this chapter is to examine the relative risk of exposure of different human populations to food‐borne aflatoxins; the types of health impact that may be incurred by dietary exposure to aflatoxins; and possible strategies likely to mitigate risks to human health. Risk of exposure is examined in a global context comparing risk of toxin exposure by levels of national socioeconomic development. Then risk of exposure is reexamined in the context of agro‐ecology, distribution of toxigenicity of Aspergillus flavus, and social factors that influence food management practices. The effects of aflatoxin exposure on human health are explored in three sections: human disease and nutritional status, carcinogenicity, and child growth and development. The section concerning mitigation of the effects of aflatoxin on human health contrasts efficacy of regulation, food basket modification, and production‐side agriculture intervention. It is concluded that risk of hepatocellular carcinoma in developing countri...