A carcinogenicity study of diphenylarsinic acid in F344 rats in drinking water for 104 weeks

• Published in: Journal of toxicological sciences Vol. 42; no. 4; pp. 475 - 483
• Main Authors: Yamaguchi, Takashi, Gi, Min, Fujioka, Masaki, Doi, Kenichiro, Okuno, Takahiro, Kakehashi, Anna, Wanibuchi, Hideki
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Society of Toxicology 2017; Japan Science and Technology Agency
• Subjects: Acids; Administration, Oral; Animals; Arsenicals - administration & dosage; Arsenicals - adverse effects; Bile ducts; Bioassays; Body Weight; Carcinogenesis; Carcinogenicity; Carcinogenicity study; Carcinogens; Chemical warfare; Chemical Warfare Agents - adverse effects; Diethylnitrosamine; Diphenylarsinic acid; Dose-Response Relationship, Drug; Drinking water; Dumping; F344 rats; Female; Females; Groundwater; Hyperplasia; Liver; Liver Neoplasms - chemically induced; Liver Neoplasms - mortality; Male; Males; Neoplasia; Neoplasms; Neurotoxicity; Organic chemistry; Rats, Inbred F344; Survival Rate; Time Factors; Tumors; Water - administration & dosage; Water Pollutants, Chemical - adverse effects; Diphenylarsinic acid; Carcinogenicity study; F344 rats
• ISSN: 0388-1350; 1880-3989
• DOI: 10.2131/jts.42.475

Diphenylarsinic acid (DPAA), a neurotoxic organic arsenical used as a chemical warfare agent, is present in the groundwater and soil in some regions of Japan due to illegal dumping after World War II. We previously demonstrated that DPAA promotes diethylnitrosamine-induced liver carcinogenesis in a medium-term rat liver bioassay. The purpose of the present study was to evaluate the potential carcinogenicity of DPAA, including investigation of whether the bile duct hyperplasia in the liver that was observed in a previous 52 week rat chronic study develops into a tumor, when administered to rats in their drinking water for 104 weeks. DPAA was administered to groups 1-4 at concentrations of 0, 5, 10, and 20 ppm in their drinking water for 104 weeks. A significant decrease in survival rate was found for females in the 20 ppm DPAA group. Body weights of males in the 20 ppm and females in the 10 and 20 ppm DPAA groups were significantly decreased compared to the controls. Overall histopathological evaluation of neoplasms in all tissues showed no significant increase of tumor incidence in any organ or tissue of the 5, 10, or 20 ppm DPAA-treated male or female F344 rats. In conclusion, the present study demonstrated that DPAA is not a complete carcinogen in male or female F344 rats.