Evaluating the mouse model for estimation of arsenic bioavailability: Comparison of estimates of absolute bioavailability of inorganic arsenic in mouse, humans, and other species

Abstract

ABSTRACT Accurate assessment of adverse health effects attributable to ingestion of inorganic arsenic (As) present in contaminated soils requires determination of the internal dose of metal provided by ingested soil. This calculation requires estimation of the oral bioavailability of soil-borne (As). Animal models to assess the bioavailability of soil (As) are frequently used as surrogates for determination of this variable in humans. A mouse assay has been widely applied to estimate the bioavailability of As in soils at sites impacted by mining, smelting, and pesticides. In the mouse assay, the relative bioavailability (RBA) of soil (As) is determined as the ratio of the fraction of the ingested arsenic dose excreted in urine after consumption of diets containing a test soil or the soluble reference compound, sodium arsenate. The aim of the current study was to compare (As) bioavailability measured in the mouse assay with reported estimates in humans. Here, a pharmacokinetic model based on excretion of arsenic in urine and feces was used to estimate the absolute bioavailability (ABA) of As in mice that received an oral dose of sodium arsenate. Based upon this analysis, in mice that consumed diet amended with sodium arsenate, the ABA was 85%. This estimate of arsenic ABA for the mouse is comparable to estimates in humans who consumed (As) in drinking water and diet, and to estimates of ABA in monkeys and swine exposed to sodium arsenate. The concordance of estimates for ABA in mice and humans provides further support for use of the mouse model in human health risk assessment. Sodium arsenate ABA also provides a basis for estimating soil arsenic ABA from RBA estimates obtained in the mouse model.