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EFFECT OF DOSE ON THE EXCRETION AND METABOLISM OF MONOMETHYLARSONIC ACID IN THE MOUSE
Citation:
Hughes, M F., V. Devesa, B C. Edwards, C T. Mitchell, E M. Kenyon, AND D J. Thomas. EFFECT OF DOSE ON THE EXCRETION AND METABOLISM OF MONOMETHYLARSONIC ACID IN THE MOUSE. Presented at Society of Toxicology, Baltimore, MD, March 21-25, 2004.
Description:
EFFECT OF DOSE ON THE EXCRETION AND METABOLISM OF MONOMETHYLARSONIC ACID IN THE MOUSE
M F Hughes1, V Devesa2, B C Edwards1, C T Mitchell1, E M Kenyon1, and D J Thomas1. 1US EPA, ORD, NHEERL, ETD, Research Triangle Park, NC; 2UNC-CH, CEMALB, Chapel Hill, NC
Monomethylarsonic acid (MMA(V)) is found in urine and tissues of mice exposed to inorganic arsenic. In addition, the sodium salts of MMA(V) are registered herbicides in the United States. The objective of this study was to determine whether administered dose affects the excretion and metabolism of this methylated arsenical. Adult female B6C3F1 mice were gavaged with MMA(V) (disodium salt) at a dose level of either 0.4 or 40 mg As/kg. Mice received either 14C-MMA(V) (N=4/dose) or unlabeled MMA(V) (N=3/dose) and were housed in metabolism cages for collection of excreta. The 24-hr cumulative urinary excretion of chemical-derived 14C was significantly greater (p < 0.05, t-test) in the low dose group (65.4 ? 9.5%) than in the high dose group (45.4 ? 11.5%). The 24-hr cumulative fecal excretion of chemical-derived 14C was significantly lower (p < 0.01, t-test) in the low dose group (38.8 ? 8.8%) than in the high dose group (61.8 ? 8.6%). Analysis of urine of mice administered unlabeled MMA(V) by hydride generation atomic absorption spectrometry revealed the presence of monomethylarsonous acid (MMA(III)), dimethylarsinous acid (DMA(III)), trimethylarsine oxide (TMAO), MMA(V) and dimethylarsinic acid (DMA(V)). Administered dose did not affect the level of the arsenicals excreted. The rank order of excreted arsenicals was MMA(V) (88%), DMA(V) (7%), TMAO (2%), DMA(III) (2%), MMA(III) (1%). Dose affects the route of excretion of MMA(V) and metabolites but not its metabolism. (This abstract does not necessarily reflect EPA policy.)