Dissolution of Mineral-Bound Arsenic in Biofluid: In Vitro Bioaccessibility in Synthetic Gastric Solution and In Vivo Distribution in Germ-Free Mice

Arsenic (As) is a naturally-occurring environmental toxicant and carcinogen of concern.Exposure to As through inhalation of dust and ingestion of contaminated particulate matter poses a human health risk to populations located near sources of As contamination, such as mining impacted communities in the desert Southwest. The relative toxicity of particle-bound As depends on its bioavailability and in vivo speciation, which is impacted by the chemical form of ingested As. Additionally, recent research evidences the role of the gut microbiome in modulating As toxicity, though the overall relationship between microbial activity and As speciation, bioavailability, and toxicity is not currently understood. This work seeks to address this knowledge gap by, 1) developing more robust analytical methods for As speciation of highly toxic methylated thioarsenic compounds by (HPLC-)ICP-MS and (LC-)ESI-MSMS, 2) chemically characterizing and assessing the in vitro bioaccessibility of As-bearing solids relevant to mine waste environments, and 3) determining the distribution of As in organs, feces, and serum of germ-free mice after ingestion of different forms of mineral-bound As relevant to mine waste environments. The results of these studies exhibit the relationship between the mineralogy and speciation of ingested particle-bound As and its in vitro bioaccessibility and in vivo distribution in germ-free mice. These results advance our understanding of As dynamics in in vitro and in vivo systems isolated from gut microbiome activity, which will contribute to our overall knowledge of the impact of the gut microbiome on As transformation and toxicity when coupled to the results of conventional mouse exposure experiments.Release after 02/23/202