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.