Arsenic speciation in bile and urine following oral and intravenous exposure to inorganic and organic arsenic in rats. Toxicol. Sci

Although inorganic arsenate (iAsV) andarsenite (iAsIII) aremeta-bolized in liver and excreted into bile and urine, the metabolites in the bile after the oral intake of iAs remain unclear. Male Sprague-Dawley ratswere orally (po) or intravenously (iv) exposed to iAs and methylated arsenics, and the arsenic speciation in the urine and bile was analyzed by high performance liquid chromatography-inductively coupled argon plasma mass spectrometry. Arsenic caused induction of multidrug resistance-associated protein 2 (MRP2), and changes of glutathione (GSH) levels in the liver and bilewere alsodetermined.Themetabolic speciation studies revealed that arsenic was excreted into bile in the methylarsenic-diglutathione (MADG) and/or dimethylarsenic acid (DMAV) forms in iAsIII- or iAsV-po rats, but that MADG and arsenic-triglutathione (ATG) are the main forms excreted into bile both in iAsIII- and iAsV-iv rats. In MADG-po rats, the MADG wa