Aflatoxin exposure in pregnant women of mixed status of human immunodeficiency virus infection and rate of gestational weight gain: a Ugandan cohort study

OBJECTIVES: To examine the association between aflatoxin (AF) exposure during pregnancy and rate of gestational weight gain (GWG) in a sample of pregnant women of mixed HIV status in Gulu, northern Uganda. METHODS: 403 pregnant women were included (133 HIV‐infected on antiretroviral therapy (ART), 270 HIV‐uninfected). Women’s weight, height and socio‐demographic characteristics were collected at baseline (~19 weeks’ gestation); weight was assessed at each follow‐up visit. Serum was collected at baseline and tested for aflatoxin B1‐lysine adduct (AFB‐lys) levels using high‐performance liquid chromatography (HPLC). Linear mixed‐effects models were used to examine the association between AFB‐lys levels and rate of GWG. RESULTS: AFB‐lys levels (detected in 98.3% of samples) were higher among HIV‐infected pregnant women than HIV‐uninfected pregnant women [median (interquartile range): 4.8 (2.0, 15.0) vs. 3.5 (1.6, 6.1) pg/mg of albumin, P < 0.0001]. Adjusting for HIV status, a one‐log increase in aflatoxin levels was associated with a 16.2 g per week lower rate of GWG (P = 0.028). The association between AFB‐lys and the rate of GWG was stronger and significant only among HIV‐infected women on ART [−25.7 g per week per log (AFB‐lys), P = 0.009 for HIV‐infected women vs. −7.5 g per week per log (AFB‐lys), P = 0.422 for HIV‐uninfected women]. CONCLUSIONS: Pregnant women with higher levels of AF exposure had lower rates of GWG. The association was stronger for HIV‐infected women on ART, suggesting increased risk.https://onlinelibrary.wiley.com/doi/10.1111/tmi.13457Published versio

Application of the U.S. EPA Mode of Action Framework for Purposes of Guiding Future Research: A Case Study Involving the Oral Carcinogenicity of Hexavalent Chromium

Mode of action (MOA) analysis provides a systematic description of key events leading to adverse health effects in animal bioassays for the purpose of informing human health risk assessment. Uncertainties and data gaps identified in the MOA analysis may also be used to guide future research to improve understanding of the MOAs underlying a specific toxic response and foster development of toxicokinetic and toxicodynamic models. An MOA analysis, consistent with approaches outlined in the MOA Framework as described in the Guidelines for Carcinogen Risk Assessment, was conducted to evaluate small intestinal tumors observed in mice chronically exposed to relatively high concentrations of hexavalent chromium (Cr(VI)) in drinking water. Based on review of the literature, key events in the MOA are hypothesized to include saturation of the reductive capacity of the upper gastrointestinal tract, absorption of Cr(VI) into the intestinal epithelium, oxidative stress and inflammation, cell proliferation, direct and/or indirect DNA modification, and mutagenesis. Although available data generally support the plausibility of these key events, several unresolved questions and data gaps were identified, highlighting the need for obtaining critical toxicokinetic and toxicodynamic data in the target tissue and in the low-dose range. Experimental assays that can address these data gaps are discussed along with strategies for comparisons between responsive and nonresponsive tissues and species. This analysis provides a practical application of MOA Framework guidance and is instructive for the design of studies to improve upon the information available for quantitative risk assessment