Biotransformation of inorganic arsenic results in the formation of methylarsenicals of both oxygen and sulfur analogues. Aiming to improve our understanding of metabolism of inorganic arsenic in animals, we conducted an animal feeding study with an emphasis on identifying new arsenic metabolites. Female F344 rats were given 0, 1, 10, 25, 50, and 100 μg/g of arsenite (iAsIII) in the diet. Arsenic species in rat urine were determined using high performance liquid chromatography (HPLC) separation and inductive coupled plasma mass spectrometry (ICPMS) and electrospray ionization tandem mass spectrometry (ESI MS/MS) detection. Nine arsenic species were detected in the urine of the iAsIII-dosed rats. Seven of these arsenic species were consistent with previous reports, including iAsIII, arsenate, monomethyarsonic acid, dimethylarsinic acid, trimethylarsine oxide, monomethylmonothioarsonic acid, and dimethylmonothioarsinic acid. Two new methyldithioarsencals, monomethyldithioarsonic acid (MMDTAV) and dimethyldithioarsinic acid (DMDTAV), were identified for the first time in the urine of rats treated with iAsIII. The concentrations of both MMDTAV and DMDTAV in rat urine were dependent on the dosage of iAsIII in diet. The concentration of DMDTAV was approximately 5 times higher than that of MMDTAV. MMDTAV has not been identified in any biological samples of animals, and DMDTAV has not been reported as a metabolite of inorganic arsenic in the rats. The identification of novel methylated dithioarsenicals as metabolites of inorganic arsenic in the rat urine provided further insights into the understanding of the metabolism of arsenic.
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