Citation:

PAUL, D., A. HERNANDEZ, F. WALTON, D. J. THOMAS, AND M. STYBLO. CHRONIC EXPOSURE TO ARSENITE IN DRINKING WATER IMPAIRS GLUCOSE TOLERANCE IN C57BL/6 MICE. Presented at Society of Toxicology Annual Meeting, Charlotte, NC, March 25 - 29, 2007.

Description:

Chronic exposures to inorganic arsenic (iAs) have been associated with increased prevalence of type 2 diabetes mellitus. This study examines in vivo diabetogenic effects of iAs in an animal model. Here, weanling male C57BL/6 mice received deionized water containing iAs(III) (25 or 50 ppm) or water without iAs(III) for 8 weeks. Body weight and water consumption were monitored throughout the study. At 8 weeks, intraperitoneal glucose tolerance was tested in all treatment groups. Skeletal muscle, pancreas, liver, and adipose tissue were collected and analyzed for arsenic species. Mice in the 25 and 50 ppm groups consumed significantly less water than did control mice. However, body weights did not differ among treatment groups. Exposure to iAs(III) resulted in impaired glucose tolerance in the 50 ppm group but not in the 25 ppm group. The ranges of concentrations of arsenic in tissues of control mice (.03 to 4.9 ng/g) were significantly lower than in mice in 25 ppm (36.9 to 422.8 ng/g) or 50 ppm (120.1 to 1165.4 ng/g) groups. Highest concentrations of arsenic were found in the liver, followed by skeletal muscle, pancreas, and adipose tissue. Dimethylarsenic was the predominant form of arsenic found in tissues of both control and iAs(III)-treated mice. Notably, the average total concentration of arsenicals in livers of mice in the 50 ppm group approximated the highest aconcentration of total arsenic in liver tissue of Bangladeshi residents who consumed water with markedly lower levels of iAs (0.22 to 2 ppm). More rapid clearance of arsenicals from target tissues in mice may account for the lower susceptibility of this species to the diabetogenic effects of iAs. (This abstract does not reflect US EPA policy.)

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