title: Carcinogenicity studies of 1,4-dioxane administered in drinking-water to rats and mice for 2 years.
abstract: The carcinogenicity of 1,4-dioxane was examined by giving groups of 50 F344/DuCrj rats and 50 Crj:BDF(1) mice of each sex 1,4-dioxane in the drinking-water for 2 years. The concentrations of 1,4-dioxane were 0 (control), 200, 1000 and 5000 ppm (wt./wt.) for rats and 0, 500, 2000 and 8000 ppm for mice. The highest dose levels did not exceed the maximum tolerated dose. In the rat, there was significant induction of nasal squamous cell carcinomas in females and hepatocellular adenomas and carcinomas in males and females, peritoneal mesotheliomas in males, and mammary gland adenomas in females. In the mouse, there was significant induction of hepatocellular tumors in males and females. Two nasal tumors occurring in the 8000 ppm-dosed groups were spontaneously rare and, thus, were attributed to 1,4-dioxane exposure. The present studies provided clear evidence of carcinogenicity in rats and mice. Lifetime cancer risk of humans exposed to 1,4-dioxane through drinking-water was quantitatively estimated with a non-threshold approach by application of a linearized multistage model to dose-carcinogenic response relationships, in addition to a threshold approach for estimation of the tolerable daily intake using no-observed- or lowest-observed-adverse-effect levels of the carcinogenic responses and uncertainty factors.
authors.affiliation: Japan Bioassay Research Center, Japan Industrial Safety and Health Association, 2445 Hirasawa, Hadano, Kanagawa 257-0015, Japan. h-kano@jisha.or.jp
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kano
authors.forename: Yumi
authors.initials: Y
authors.lastname: Umeda
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kasai
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sasaki
authors.forename: Michiharu
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Kazunori
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Kasuke
authors.initials: K
authors.lastname: Nagano
authors.forename: Heihachiro
authors.initials: H
authors.lastname: Arito
authors.forename: Shoji
authors.initials: S
authors.lastname: Fukushima
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage* / Q000633:toxicity*; D004146:Dioxanes / Q000008:administration & dosage* / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D008136:Longevity / Q000187:drug effects; D008297:Male; D051379:Mice; D051381:Rats; D011916:Rats, Inbred F344; D012727:Sex Characteristics
chemical_list: D002273:Carcinogens; D004146:Dioxanes; C025223:1,4-dioxane