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DOSE DEPENDENT DISPOSITION OF SODIUM ARSENATE IN MICE FOLLOWING ACUTE ORAL EXPOSURE
Citation:
Hughes, M., D. Thompson, AND M. Menache. DOSE DEPENDENT DISPOSITION OF SODIUM ARSENATE IN MICE FOLLOWING ACUTE ORAL EXPOSURE. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-94/329 (NTIS PB94202140), 1994.
Description:
The effect of dose on arsenate disposition was studied in adult female B6C3F, mice, dosed po with 0.5 to 5000 ug/kg [73As]-arsenate in water. rine was collected at 1, 2, 4, 8, 12, 24 and 48 hr and feces at 24 and 48 hr postexposure. he mice were sacrificed at 48 hr and tissues were removed. ecovery of arsenate-derived radioactivity ranged from 83 to 89%; 66-79% of the dose was excreted in urine, 10-18% in feces, and <1% remained in the tissues. lthough dose had no effect on the 48-hr excretion of radioactivity, the level of radioactivity in several tissues increased significantly with dose. he urine was analyzed for arsenic metabolites by using ion chromatography to analyze for arsenate, methylarsonic acid (MMA), and dimethylarsinic acid (DMA); ion-pairing high-performance liquid chromatography was used for arsenite analysis. rsenate elimination ranged from 3 to 15%. MA was the predominant metabolite (51-64% of dose) excreted, but no effect of dose on its elimination was detected. s the dose of arsenate increased, the amount of MMA excreted (0.1-1.0% of dose) significantly increased. t 5000 ug/kg arsenate, a significant increase in arsenite excretion was observed. t doses of arsenate < 500 pig/kg, peak elimination of DMA occurred within 4 hr postexposure at 5000 ug/kg, DMA peak elevation shifted to 8 hr and a lower amount was excreted. n addition, at the 5000-ug/kg dose, there was an increase of arsenate and arsenate in the 1- and 2-hr urine. he results suggest that an acute dose of arsenate can affect the metabolism of arsenicals, leading to the accumulation of intermediates that are more reactive than DMA, which may lead to increased toxicity.
