title: A chronic toxicity study of diphenylarsinic acid in F344 rats in drinking water for 52 weeks.
abstract: Diphenylarsinic acid (DPAA), a chemical warfare-related neurotoxic organic arsenical, is present in the groundwater and soil in some regions of Japan due to illegal dumping after World War II. The purpose of the present study was to evaluate the potential toxicity of DPAA when administered to rats in their drinking water for 52 weeks. DPAA was administered to groups 1-4 at concentrations of 0, 5, 10, and 20ppm in their drinking water for 52 weeks. There were no significant differences in the final body weights between the control groups and the treatment groups in male or female rats. In serum biochemistry, in females 20ppm DPAA significantly increased alkaline phosphatase and γ-glitamyl transferase compared to controls, and 10 and 20ppm DPAA significantly increased total cholesterol compared to controls. Absolute and relative liver weights were significantly increased in females treated with 20ppm DPAA compared to the control group. Dilation of the common bile duct outside the papilla of Vater and stenosis of the papilla of Vater was observed in all male and female rats administered 20ppm DPAA. The incidence of intrahepatic bile duct hyperplasia was significantly increased in male and female rats treated with 20ppm DPAA compared to the control groups. These results suggest that DPAA is toxic to the bile duct epithelium in rats. The no-observed adverse effect levels of DPAA were estimated to be 10ppm (0.48mg/kg b.w./day) for males and 5ppm (0.35mg/kg b.w./day) for females under the conditions of this study.
authors.affiliation: Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Min
authors.initials: M
authors.lastname: Gi
authors.affiliation: Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan; Division of Rare Cancer Research National Cancer Center Research Institute, Tsukiji 5-5-1, Chuo-ku Tokyo 104-0045, Japan.
authors.forename: Shotarou
authors.initials: S
authors.lastname: Yamano
authors.affiliation: Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Fujioka
authors.affiliation: Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Tatsumi
authors.affiliation: Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Kawachi
authors.affiliation: Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Ishii
authors.affiliation: Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Doi
authors.affiliation: Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Anna
authors.initials: A
authors.lastname: Kakehashi
authors.affiliation: Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. Electronic address: wani@med.osaka-cu.ac.jp.
authors.forename: Hideki
authors.initials: H
authors.lastname: Wanibuchi
mesh_terms: D000818:Animals; D001152:Arsenicals / Q000009:adverse effects*; D001652:Bile Ducts / Q000187:drug effects*; D002908:Chronic Disease; D060766:Drinking Water; D005260:Female; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D001152:Arsenicals; D060766:Drinking Water; C493087:diphenylarsinic acid
keywords: Bile duct toxicity; Chronic toxicity; Diphenylarsinic acid; F344 rats