title: Carcinogenicity of ortho-phenylenediamine dihydrochloride in rats and mice by two-year drinking water treatment.
abstract: The carcinogenicity of ortho-phenylenediamine (o-PD) was examined by administrating o-phenylenediamine dihydrochloride (o-PD2HCl) in dinking water to groups of 50 F344/DuCrj rats and 50 Crj:BDF₁ mice of both sexes for 2 years. The drinking water concentration of o-PD2HCl was 0, 500, 1,000 or 2,000 ppm (wt/wt) for male rats; 0, 250, 500 or 1,000 ppm for female rats; 0, 500, 1,000 or 2,000 ppm for male mice; and 0, 1,000, 2,000 or 4,000 ppm for female mice. Two-year administration of o-PD2HCl produced a dose-dependent increase in the incidences of hepatocellular adenomas and carcinomas in rats of both sexes and in female mice, and hepatocellular adenomas in male mice. In mice, the incidences of hepatocellular adenomas were increased at the lowest dose used in both males and females. Metastasis from hepatocellular carcinomas of rats occurred predominantly in the lung. Incidences of transitional cell papillomas and carcinomas in the urinary bladder were noted in male rats administered 2,000 ppm, together with an increased incidence of papillary and/or nodular hyperplasia of transitional epithelium. In mice, the incidence of papillary adenomas in the gall bladder, which is rare in mice, was increased in both males and females administered 2,000 ppm. Thus, o-PD is carcinogenic in two species, i.e., rats and mice of both sexes.
authors.affiliation: Japan Bioassay Research Center, Japan Industrial Safety and Health Association, 2445 Hirasawa, Hadano, Kanagawa 257-0015, Japan. m-matsumoto@jisha.or.jp
authors.forename: Michiharu
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Masaaki
authors.initials: M
authors.lastname: Suzuki
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kano
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Aiso
authors.forename: Kazunori
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Shoji
authors.initials: S
authors.lastname: Fukushima
mesh_terms: D000236:Adenoma / Q000139:chemically induced / Q000401:mortality; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests / Q000379:methods; D002273:Carcinogens / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000401:mortality; D004305:Dose-Response Relationship, Drug; D060766:Drinking Water; D005260:Female; D008113:Liver Neoplasms / Q000139:chemically induced / Q000401:mortality; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D010655:Phenylenediamines / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000401:mortality
chemical_list: D002273:Carcinogens; D060766:Drinking Water; D010655:Phenylenediamines; C034193:1,2-diaminobenzene