"Foodborne mycotoxins are low molecular weight secondary metabolites produced by fungi and commonly co-occur in staple crops such as wheat, barley, and corn. Hence, they jointly cause adverse effects including decreased growth and immune system dysfunction. However, there is limited information on their relative toxicities which makes risk assessment difficult. As a result, current mycotoxin regulations are mostly based on individual toxin studies conducted using animal models and in some instances, supplemented with very limited epidemiological data. This dissertation presents aflatoxin exposure data of Ugandan children aged 1-5 years and also presents relative toxicities of trichothecenes that commonly co-occur in food. To assess the level of aflatoxin exposure among the children, we conducted a cross sectional survey in three regions (chapter 2). We used isotope dilution mass spectrometry to determine the concentration of aflatoxin B1-lysine adducts in their serum. We found detectable concentrations of these bioimarkers in all samples that were tested. We observed differences in aflatoxin exposure among regions, but there were no significant differences in exposure by age group, sex, and residence type. The levels of aflatoxin exposure among Ugandan children are consistent with concentrations associated with growth impairment in other epidemiological studies. Using case studies of aflatoxin and cassava cyanide, we discussed the heightened risk of particular diseases from consuming monotonous diets based on maize, groundnuts, and cassava (chapter 3). We discussed the potential role of increased dietary diversity in counteracting these diseases. Studies show that, increased dietary diversity can reduce consumption of toxins and increase intake of nutrients that could counteract the toxicity of such chemicals. Because interventions focused solely on reducing toxin levels have proven difficult to sustain, we suggest that future food policy reforms should take into consideration the multifaceted benefits associated with improved dietary diversity to promote health. To address the issue of co-occurrence of in food, we proposed assigning of toxic equivalency factors (TEFs) to mycotoxins that have similarities in their mode of action. Here, we employed a mouse model to compare the oral exposure anorectic potencies of simple trichothecenes using the US Environmental Protection Agency (US-EPA) benchmark dose (BMD) method and the incremental area under the curve (IAUC) method (chapter 4). The relative potencies of these toxins were calculated as the ratios of their BMDs (or IAUC) to that of DON. The rank orders for anorectic potency were: DON 2248 3-ADON 2248 15-ADON < NIV < HT-2 < FUS-X << T-2 and DON < 3-ADON 2248 15-ADON < NIV < FUS-X << T-2 < HT-2 for the BMD and IAUC method, respectively. We also used a mink emesis model and the BMD method to compare the toxicities of the trichothecenes administered via gavage and intraperitoneally (chapter 5). Our results showed that mink were more sensitive to orally administered toxins than to toxins administered by IP. The rank order for the oral emetic potency was: HT-2 2248 T-2 > FX > DON > 15-ADON > NIV > 3-ADON. Taken together, the results presented in this dissertation demonstrate that assigning of TEFs for trichothecenes that co-occur in food is possible."--Pages ii-iii.
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