Effects of aflatoxin on the immune system: Evidence from human and mammalian animal research.

Shortly after its discovery in 1960, aflatoxin - a group of fungal toxins or mycotoxins produced by the fungi Aspergillus flavus and A. parasiticus in food crops such as maize, peanuts and tree nuts - was found to cause liver cancer in humans and multiple animal species. Hence, regulations on maximum allowable aflatoxin levels in food worldwide have focused on protecting humans from aflatoxin's carcinogenic effects. However, aflatoxin may also have non-carcinogenic health effects (e.g., immunotoxicity) that are particularly relevant today. Our current review highlights the growing evidence that aflatoxin exposure adversely affects immunity. Here, we comprehensively evaluated human and mammalian animal studies that link aflatoxin exposure with adverse effects on the immune system. We organized the review by organism as well as by the effects on adaptive and innate immune functions. There is abundant evidence that aflatoxin exhibits immunotoxicity, and therefore may compromise the ability of both humans and animals to resist infections. However, the reported effects of aflatoxin on certain specific immune biomarkers are inconsistent in the existing literature. The extent of the immunotoxic effects of aflatoxin must be clarified, so that the contribution of such immunotoxicity to the overall burden of aflatoxin-related diseases can be established.

Estimation of Tolerable Daily Intake (TDI) for Immunological Effects of Aflatoxin.

Aflatoxins are toxic chemicals produced by the fungi Aspergillus flavus and Aspergillus parasiticus. In warm climates, these fungi frequently contaminate crops such as maize, peanuts, tree nuts, and sunflower seeds. In many tropical and subtropical regions of the world, populations are coexposed to dietary aflatoxin and multiple infectious pathogens in food, water, and the environment. There is increasing evidence that aflatoxin compromises the immune system, which could increase infectious disease risk in vulnerable populations. Our aim was to conduct a dose-response assessment on a noncarcinogenic endpoint of aflatoxin: immunotoxicological effects. We sought to determine a noncarcinogenic tolerable daily intake (TDI) of aflatoxin, based on the existing data surrounding aflatoxin and biomarkers of immune suppression. To conduct the dose response assessment, mammalian studies were assessed for appropriateness of doses (relevant to potential human exposures) as well as goodness of data, and two appropriate mouse studies that examined decreases in leukocyte counts were selected to generate dose response curves. From these, we determined benchmark dose lower confidence limits (BMDL) as points of departure to estimate a range of TDIs for aflatoxin-related immune impairment: 0.017-0.082 µg/kg bw/day. As aflatoxin is a genotoxic carcinogen, and regulations concerning its presence in food have largely focused on its carcinogenic effects, international risk assessment bodies such as the Joint Expert Committee on Food Additives (JECFA) have never established a TDI for aflatoxin. Our work highlights the importance of the noncarcinogenic effects of aflatoxin that may have broader public health impacts, to inform regulatory standard-setting.

A review of biogenic amines in fermented foods: Occurrence and health effects.

Biogenic amines (BAs) are low-molecular decarboxylation products of amino acids formed during microbial fermentation. Several fermented foods may contain BAs such as histamine, tyramine, and/or phenylethylamine, at levels above documented toxic doses. Dietary exposure to foods containing high levels of BAs is associated with many adverse health effects, such as migraines, elevated blood pressure, and tachycardia. BA-mediated toxicity may occur at levels a hundred times below regulatory and suggested toxic doses, depending on an individual's sensitivity and factors such as alcohol consumption and certain medications. Although BAs occur in a wide variety of fermented foods, food safety and public health professionals are not well informed about the potential health risks and control strategies in these foods. In this review, we highlight the health risks and symptoms linked to BA exposures, the BA levels found in different fermented foods, regulatory and suggested toxic doses, and risk mitigation strategies to inform food industry and public health professionals' practice.

Characterization of the short-term temporal variability of road dust chemical mixtures and meteorological profiles in a near-road urban site in British Columbia.

Implications: Non-tailpipe emissions driven by springtime road dust in northern latitude communities is increasing in importance for air pollution control and improving our understanding of the health effects of chemical mixtures from particulate matter exposure. High-volume samples from a near-road site indicated that days affected by springtime road dust are substantively different from other days with respect to particulate matter mixture composition and meteorological drivers. The high load of trace elements in PM10 on high road dust days has important implications for the acute toxicity of inhaled air and subsequent health effects. The complex relationships between road dust and weather identified in this study may facilitate further research on the health effects of chemical mixtures related to road dust while also highlighting potential changes in this unique form of air pollution as the climate changes.

Aflatoxin M1 in milk does not contribute substantially to global liver cancer incidence.

BACKGROUND: For 60 y, it has been known that aflatoxin B1 (AFB1), a mycotoxin produced by Aspergillus fungi in certain food and feed crops, causes hepatocellular carcinoma (liver cancer; HCC) in humans. The annual global burden of AFB1-related HCC has been estimated. However, much less is known about the potential carcinogenic impact of a metabolite of AFB1 called aflatoxin M1 (AFM1), which is secreted in milk when dairy animals consume AFB1-contaminated feed. The cancer risk of AFM1 to humans from milk consumption has not yet been evaluated. OBJECTIVES: We sought to estimate the global risk of AFM1-related liver cancer through liquid milk consumption, accounting for possible synergies between AFM1 and chronic infection with hepatitis B virus (HBV) in increasing cancer risk. METHODS: We conducted a quantitative cancer risk assessment by analyzing extensive datasets of national population sizes, dairy consumption patterns, AFM1 concentrations in milk in 40 nations, and chronic HBV prevalence. Two separate cancer risk assessments were conducted: assuming a possible synergy between AFM1 and HBV in increasing cancer risk in a manner similar to that of AFB1 and HBV, and assuming no such synergy. RESULTS: If there is no synergy between AFM1 and HBV, AFM1 may contribute ∼0.001% of total annual HCC cases globally. If there is synergy between AFM1 and HBV infection, AFM1 may contribute ∼0.003% of all HCC cases worldwide. In each case, the total expected AFM1-attributable cancer cases are ∼13-32 worldwide. CONCLUSION: AFM1 exposure through liquid milk consumption does not substantially increase liver cancer risk in humans. Policymakers should consider this low risk against the nutritional benefits of milk consumption, particularly to children, in a current global situation of milk being discarded because of AFM1 concentrations exceeding regulatory standards.

Risk assessment of aflatoxin-related liver cancer in Bangladesh.

Aflatoxins are mycotoxins (fungal toxins) produced by Aspergillus species in variety of food commodities. Consumption of aflatoxin-contaminated food can cause adverse health effects, including liver cancer. Aflatoxin exposure is usually higher in hot and humid countries. Previous biomarker-based studies have indicated significant exposure to aflatoxins among the Bangladeshi population. Recently, high aflatoxin levels were reported in dates, which are consumed in large quantities during the month of Ramadan in Bangladesh and other Muslim countries. Bangladesh has recently enacted aflatoxin regulation in foods. In this study, we determined the risk of aflatoxin-related liver cancer among the Bangladeshi population based on the average dietary intakes of different aflatoxin contaminated foods, accounting for the synergistic impacts of aflatoxin with chronic hepatitis B viral infection in inducing cancer. We also determined whether the new aflatoxin regulations in Bangladesh could significantly reduce the risk of liver cancer. The mean number of cancer cases per year caused by dietary aflatoxin exposure in Bangladesh was estimated at about 1311, or 43.9% of the total annual liver cancer cases in Bangladesh. The new aflatoxin regulations do not appear likely to significantly reduce the risk of liver cancer in the country.