A chronic toxicity study of diphenylarsinic acid in the drinking water of C57BL/6J mice for 52 weeks.

A chronic toxicity study of diphenylarsinic acid in the drinking water of C57BL/6J mice for 52 weeks. J Toxicol Pathol. 2019 Jul;32(3):127-134 Authors: Yamaguchi T, Gi M, Fujioka M, Tago Y, Kakehashi A, Wanibuchi H Abstract Diphenylarsinic acid (DPAA), a neurotoxic organic arsenical, is present in the groundwater and soil in some regions of Japan due to illegal dumping. The purpose of the present study was to evaluate the potential toxicity of DPAA when administered to mice in their drinking water for 52 weeks. DPAA was administered to mice at concentrations of 0, 6.25, 12.5, and 25 ppm in their drinking water for 52 weeks. There were no significant differences in final body weights between the control groups and the DPAA treatment groups in male or female mice. Relative liver weights were significantly increased in males treated with 25 ppm DPAA, and absolute liver weights were significantly decreased in female mice treated with 25 ppm DPAA. In female mice, cholangitis and simple bile duct hyperplasia were observed in the 12.5 and 25 ppm DPAA groups, and focal necrosis of hepatocytes was observed in the 25 ppm DPAA group. Proteomic analysis and Ingenuity Pathway Analysis identified 18 proteins related to hepatotoxicity that were overexpressed in the female 25 ppm group. The phase I metabolic enzyme CYP2E1 was one of these overexpressed proteins. Immunostaining confirmed high expression of CYP2E1 in the livers of females in the 25 pp...
Source: Journal of Toxicologic Pathology - Category: Toxicology Tags: J Toxicol Pathol Source Type: research