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DETERMINATION OF URINARY TRIVALENT ARSENICALS (MMASIII AND DMASIII) IN INDIVIDUALS CHRONICALLY EXPOSED TO ARSENIC
Del Razo, L. M., M. Styblo, W. R. Cullen, AND D J. Thomas. DETERMINATION OF URINARY TRIVALENT ARSENICALS (MMASIII AND DMASIII) IN INDIVIDUALS CHRONICALLY EXPOSED TO ARSENIC. Presented at SOT, San Francisco, CA, March 25-29, 2001.
DETERMINATION OF URINARY TRIVALENT ARSENICALS (MMAsIII and DMAsIII) IN INDIVIDUALS CHRONICALLY EXPOSED TO ARSENIC.
L. M. Del Razo1, M. Styblo2, W. R. Cullen3, and D.J. Thomas4.
1Toxicology Section, Cinvestav-IPN, Mexico, D.F., 2Univ. North Carolina, Chapel Hill, NC; 3Univ. British Columbia, Vancouver, BC, Canada; 4NHEERL, ORD, U.S. E PA, Research Triangle Park, NC
The trivalent methylarsenicals, monomethylarsonous acid (MMAsIII) and dimethylarsinous acid (DMAsIII) are intermediates in the biotransformation of inorganic arsenic (iAs). They are produced by the reduction of monomethylarsonic acid (MMAsV) and dimethylarsinic acid (DMAsV) and may be the favored substrates for the enzymes that methylate arsenicals. Trivalent methylated arsenicals are more cytotoxic than iAsIII and MMAsIII and DMAsIII are more potent in vitro inhibitors of enzymes with fundamental role in maintaining cellular redox-status (glutathione reductase and thioredoxin reductase) than are either iAsV or iAsIII. Hence, these metabolites may contribute significantly to the adverse effects associated with chronic exposure to iAs. Here we report a method for the determination of trivalent arsenicals in urine using a pH-dependent selective generation of arsines from AsIII and AsV detected by atomic absorption spectroscopy and its application to analysis of urine from As-exposed individuals. MMAsIII accounted for 0.7 to 1.7% and DMAsIII for 4 to 18% of the As in urine from people chronically exposed to iAs in drinking water. Because these metabolites may be more toxic than iAs, they may be a useful biomarker for exposure and effect of chronic exposure to iAs in drinking water. (This abstract does not necessarily reflect policy of the U.S. Environmental Protection Agency.)