title: Promotion of liver and kidney carcinogenesis by ethyl tertiary-butyl ether (ETBE) in male Wistar rats.
abstract: Tumor-promoting effects of ethyl tertiary-butyl ether (ETBE) were investigated in a 2-stage carcinogenesis bioassay with regard to hepatic and renal carcinogenesis in rats. Male 6-week-old Wistar rats were given drinking water containing N-ethyl-N-(2-hydroxyethyl)nitrosamine (EHEN), as an initiator, at a dose of 500 ppm for 2 weeks. Starting one week thereafter, the animals were administered ETBE at dose levels of 0 (control), 100, 300, 500 or 1,000 mg/kg/day by gavage for 19 weeks from week 4 to 22. Necropsy of all rats was performed at week 23, and livers and kidneys were examined histopathologically. Incidences of hepatocellular adenomas, and those of combined hepatocellular adenomas and carcinomas were significantly elevated in rats given 1,000 mg/kg/day ETBE, but not 100‒500 mg/kg/day ETBE, and there was a significant increase in the average numbers of lesions. No significant differences in incidences and average numbers of renal tubule neoplasms were found in rats administered 100‒1,000 mg/kg/day ETBE. However, the average numbers of atypical tubule hyperplasias, considered to be preneoplastic lesions, were significantly increased in rats given ETBE at 1,000 mg/kg/day, but not in rats given 500 mg/kg/day or lower doses. Thus, these results imply that ETBE has hepatic and renal tumor-promoting activities that affect EHEN-induced carcinogenesis in male rats, and the no-observed-effect level is 500 mg/kg/day under the present experimental conditions.
authors.affiliation: DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hagiwara
authors.affiliation: DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Doi
authors.affiliation: DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Imai
authors.affiliation: DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Suguro
authors.affiliation: DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Kawabe
authors.affiliation: DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Furukawa
authors.affiliation: DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113, Japan.
authors.forename: Seiko
authors.initials: S
authors.lastname: Tamano
authors.affiliation: Nagano Toxicologic-Pathology Consulting, 467-7 Ojiri, Hadano, Kanagawa 257-0011, Japan.
authors.forename: Kasuke
authors.initials: K
authors.lastname: Nagano
authors.affiliation: Japan Bioassay Research Center, Japan Industrial Safety and Health Association, 2445 Hirasawa, Hadano, Kanagawa 257-0015, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Fukushima
keywords: N-ethyl-N-(2-hydroxyethyl)nitrosamine; Wistar rat; ethyl tertiary-butyl ether; hepatic carcinogenesis; renal carcinogenesis; tumor promotion