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TISSUE DISPOSITION OF DIMETHYLARSINIC ACID IN THE MOUSE AFTER ACUTE ORAL ADMINISTRATION
Citation:
Hughes, M F., B C. Edwards, C T. Mitchell, AND E M. Kenyon. TISSUE DISPOSITION OF DIMETHYLARSINIC ACID IN THE MOUSE AFTER ACUTE ORAL ADMINISTRATION. Presented at Fifth International Conference on Arsenic Exposure and Health Effects, San Diego, CA, July 14-18, 2002.
Description:
TISSUE DISPOSITION OF DIMETHYLARSINIC ACID IN THE MOUSE
AFTER ACUTE ORAL ADMINISTRATION
Michael F. Hughes, Ph.D., Brenda C. Edwards, Carol T. Mitchell and Elaina M. Kenyon, Ph.D. United States Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Research Triangle Park, North Carolina
Dimethylarsinic acid (DMA(V)) is a tumor promoter in rodents, a bladder carcinogen in rats, and the major metabolite excreted by most mammals after exposure to inorganic arsenic. This study examined the disposition of DMA-derived radioactivity (14C) in tissues over time after acute oral administration.
Adult female mice (N=3-4/time point) were administered [14C]-DMA(V) orally (0.6 or 60 mg As/kg) and sacrificed (0.25-24 hr). Tissues were removed and analyzed for 14C.
At the earliest time point, 14C was detected in all tissues and concentrations of 14C (% dose/gm tissue) in kidney, liver, and lung were greater than in blood. The time to peak 14C concentration in the tissues occurred between 0.5-2 hr after administration and ranged from 0.4-2.6%. The lung from the low dose group and the kidney from the high dose group had the highest concentration (2.6%) of 14C. There was no dose-dependent effect on peak tissue concentration of 14C. By 24 hr, the tissue concentrations of 14C were considerably lower than observed at 0.25 hr. In kidney, liver, or lung at this time, approximately 0.01% of the dose/gm tissue or lower was detected, and the concentrations of 14C in these tissues were greater than in blood.
DMA(V) is rapidly absorbed, distributed, and excreted from the mouse after acute oral administration. The low acute toxicity of DMA(V) in the mouse appears to be due in part to its minimal retention and rapid elimination. (This abstract does not necessarily reflect EPA policy.)
CORRESPONDING AUTHOR: Michael F. Hughes, Ph.D., US EPA, NHEERL, MD-74, Research Triangle Park, NC 27711 USA