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COMPARATIVE METABOLISM OF ARSENIC IN MICE AFTER A SINGLE OR REPEATED ORAL ADMINISTRATION OF ARSENATE
Citation:
Hughes, M F., E M. Kenyon, B C. Edwards, C T. Mitchell, L. M. Del Razo, AND D J. Thomas. COMPARATIVE METABOLISM OF ARSENIC IN MICE AFTER A SINGLE OR REPEATED ORAL ADMINISTRATION OF ARSENATE. Presented at Inter. Society for Study of Xenobiotics, Providence, RI, October 12-16, 2003.
Description:
COMPARATIVE METABOLISM OF ARSENIC IN MICE AFTER A SINGLE OR REPEATED ORAL ADMINISTRATION OF ARSENATE
Michael F. Hughes*1, Elaina M. Kenyon1, Brenda C. Edwards1, Carol T. Mitchell1, Luz Maria Del Razo2 and David J. Thomas1
1US EPA, ORD, NHEERL, ETD, PKB, Research Triangle Park, NC 27711
2CINVESTAV-IPN, Mexico City, Mexico
Exposure to the human carcinogen inorganic arsenic (iAs) occurs daily. However, the disposition of iAs after repeated exposure in laboratory animals is not well studied. This study compared the tissue disposition of iAs after a single or repeated po administration of arsenate. Adult female mice were administered either a single or nine daily po doses of arsenate (0.5 mg As/kg). Mice were euthanized 24 h after the last dose, and tissues (bladder, blood, kidney, liver, lung) were analyzed for total and speciated arsenic by atomic absorption spectrometry. Blood had the lowest concentration of total arsenic after both exposures, indicating uptake of arsenic by the organs. Total arsenic preferentially accumulated in the bladder and kidney after both exposures. Bladder and lung had the highest percentage of dimethylarsinic acid (DMA(V)) after the single dose, and it increased with repeated doses. Monomethylarsonic acid was detected in all tissues except the bladder. In kidney, iAs was predominant after both exposures. There was a higher percentage of DMA(V) in the liver than the other arsenicals after a single dose, but it decreased and that of iAs increased with repeated doses. A trimethylated metabolite was also detected in the liver. Arsenic accumulates in the tissues of mice after a single and repeated exposure to arsenate and the exposures also affect the tissue-specific distribution of arsenic metabolites. (This abstract does not represent US EPA policy.)