Metabolism and disposition of arsenic species from controlled oral dosing with sodium arsenite in adult female CD-1 mice. I. Pilot study to determine dosing, analytical measurements, and sampling strategies

摘要

Abstract Arsenic (As) is ubiquitous in the earth's crust, with typical dietary intake in developed countries V ) was the predominant species in blood and urine. Consistent evidence was observed for a non-linear relationship between doses above 50?μg/kg bw and levels of bound trivalent As metabolites. The abundance of protein-bound trivalent arsenic within target tissues should correlate with disruption of critical cellular processes, which rely on defined interactions of thiol functional groups, and could provide dose-response relationships from animal models for human risk assessment. Highlights ? Metabolism of arsenite contributes to tissue binding of trivalent As species. ? Nonlinearity of arsenic pharmacokinetics was observed at doses above 50?μg/kg bw. ? Facile mobilization of bound arsenic is facilitated by cellular levels of GSH. ? Renal excretion of DMA V is the predominant elimination pathway.