Carcinogenicity studies of 1,4-dioxane administered in drinking-water to rats and mice for 2 years

Kano, H; Umeda, Y; Kasai, T; Sasaki, T; Matsumoto, M; Yamazaki, K; Nagano, K; Arito, H; Fukushima, S

HERO ID

594539

Reference Type

Journal Article

Year

2009

Language

English

PMID

19703511

HERO ID 594539
In Press No
Year 2009
Title Carcinogenicity studies of 1,4-dioxane administered in drinking-water to rats and mice for 2 years
Authors Kano, H; Umeda, Y; Kasai, T; Sasaki, T; Matsumoto, M; Yamazaki, K; Nagano, K; Arito, H; Fukushima, S
Journal Food and Chemical Toxicology
Volume 47
Issue 11
Page Numbers 2776-2784
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.
Doi 10.1016/j.fct.2009.08.012
Pmid 19703511
Wosid WOS:000272013400014
Is Certified Translation No
Dupe Override No
Is Public Yes
Language Text English
Keyword 1,4-dioxane; rat; mouse; liver; nasal cavity; tumor
Is Qa No