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COMPARATIVE TISSUE DISTRIBUTION AND URINARY EXCRETION OF INORGANIC ARSENIC (IAS) AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ORAL ADMINISTRATION OF ARSENATE (ASV) AND ARSENITE (ASIII)
Citation:
Kenyon, E M., L. M. Del Razo, AND M F. Hughes. COMPARATIVE TISSUE DISTRIBUTION AND URINARY EXCRETION OF INORGANIC ARSENIC (IAS) AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ORAL ADMINISTRATION OF ARSENATE (ASV) AND ARSENITE (ASIII). Presented at Society of Toxicology 42nd Annual Meeting, Salt Lake City, Utah, March 9-13, 2003.
Description:
COMPARATIVE TISSUE DISTRIBUTION AND URINARY EXCRETION OF INORGANIC ARSENIC (iAs) AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ORAL ADMINISTRATION OF ARSENATE (AsV) AND ARSENITE (AsIII). E M Kenyon, L M Del Razo and M F Hughes. U.S. EPA, ORD, NHEERL, ETD, PKB, RTP, NC, USA; CINVESTAV-IPN, Mexico City, Mexico
Valence state is a critical determinant in the disposition and metabolism of pentavalent compared to trivalent inorganic arsenic. In this analysis, the time-course tissue distribution of iAs and its methylated metabolites, monomethyl arsenic (MMA) and dimethyl arsenic (DMA), were compared in blood, liver, lung, kidney and urine of female B6C3F1 mice given equivalent oral doses (0, 10 or 100 mol/kg) of sodium arsenate or sodium arsenite. The concentration of iAs in both blood and liver were very similar at earlier time points (1 to 8 hours post dosing); however by 24 hours levels of iAs in liver of AsIII-dosed mice were 5-fold higher, most likely due to binding of AsIII. MMA and DMA levels in blood were generally higher following AsIII compared to AsV administration; this is most likely a consequence of more rapid initial absorption at early time points and release from bound sites with subsequent metabolism at later time points. Kidney concentrations for iAs, MMA and DMA were generally higher (up to three-fold) following AsV compared to AsIII administration reflecting the more rapid urinary excretion of total As following AsV administration. Levels of MMA measured in kidney following AsV administration are not reflected in amounts excreted in urine suggesting the possibility of sequestration. DMA is preferentially accumulated in lung following either AsV or AsIII administration; two-fold higher levels are achieved following AsV administration, but levels are maintained higher for a longer time period following AsIII administration. These data demonstrate distinct organ-specific differences in the distribution of metabolites following administration of comparable doses of AsV and AsIII that will be important to consider when investigating mechanisms of arsenic-induced toxicity. (This abstract does not necessarily reflect EPA policy.)