Dietary arsenic species exposure, metabolism, and toxicity

Substantial gaps exist in our knowledge of exposure and in our understanding of the metabolism, dose, and toxicity of diverse arsenic compounds in foods. The goal of this Pilot Project was to determine the acute alterations in metabolism and toxicity of arsenicals ingested in foods in humans and mice. In the current mouse study, arsenic metabolism and biomarker expression was investigated and the elements of organ-specific metabolism were evaluated. The effects of human and mouse gut microbiome on the methylation of dietary arsenic and related biomarkers were also considered, the findings of which facilitated the detailed characterization and pharmacokinetic modeling of the metabolism of these compounds and provided support for improved risk assessment strategies. Preliminary data show that arsenic in rice produces methylated arsenic species in urine. However, not all of the arsenicals are accounted for, indicating that other currently unidentified metabolites are present. Ingestion in foods also resulted in increased serum expression of matrix metalloproteinase-9 as has previously been shown following the ingestion of arsenic in water.