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METABOLISM AND TISSUE DOSIMETRY OF PENTAVALENT AND TRIVALENT MONOMETHYLATED ARSENIC AFTER ORAL
Citation:
Hughes, M F., B. Adair, E M. Kenyon, D J. Thomas, V. Devesa, AND M. Styblo. METABOLISM AND TISSUE DOSIMETRY OF PENTAVALENT AND TRIVALENT MONOMETHYLATED ARSENIC AFTER ORAL. Presented at Society of Toxicology Annual Meeting, New Orleans, LA, March 06 - 10, 2005.
Description:
METABOLISM AND TISSUE DOSIMETRY OF PENTAVALENT AND TRIVALENT MONOMETHYLATED ARSENIC AFTER ORAL ADMINISTRATION IN MICE
M F Hughes1, V Devesa2, B M Adair1, M Styblo2, E M Kenyon1, and D J Thomas1. 1US EPA, ORD, NHEERL, ETD, Research Triangle Park, NC; 2UNC-CH, CEMALB, Chapel Hill, NC
Humans are exposed to monomethylarsonic acid (MMA(V)) and monomethylarsonous acid (MMA(III)) formed as metabolites of inorganic arsenic. The sodium salts of MMA(V) are also used as herbicides. This study was to examined the metabolism and tissue dosimetry of MMA(V) and MMA(III). Adult female B6C3F1 mice were gavaged with either MMA(V) (0.4 or 40 mg As/kg; 14C or unlabeled) or unlabeled MMA(III) (0.4 mg As/kg). Mice were sacrificed over 24 hr and tissues (blood, bladder, kidney, liver, lung) were removed and analyzed either for radioactivity or for MMA or dimethylarsenic acid (DMA) by hydride generation-atomic absorption spectrometry. MMA(V)-derived radioactivity (14C) was rapidly absorbed and distributed among all tissues examined. Peak tissue concentrations of 14C were observed between 1 and 4 hr post-dosing. Terminal tissue half-lives ranged from 4 (liver) to 15 hr (kidney). For the two dosage levels, differences between the area under the curves (AUC) of the concentration-time profiles of 14C in the blood and organs were less than 100-fold. Only carcass, which consisted of tissues not removed and intestinal contents, had a 100-fold difference in AUC. These findings suggests that absorption of MMA(V) was dose-dependent. Speciation of arsenicals in mice receiving MMA(V) or MMA(III) found greater than five-fold more DMA in tissues in MMA(III)-treated mice than in MMA(V)-treated mice. Thus, dose and oxidation state of monomethylated arsenic can affect its disposition. (This abstract does not necessarily reflect EPA policy.)