Carcinogenicity of butyl 2,3-epoxypropyl ether in rats and mice by whole body inhalation for two years

• Published in: Journal of toxicological sciences Vol. 45; no. 1; pp. 1 - 14
• Main Authors: Matsumoto, Michiharu, Kasai, Tatsuya, Saito, Arata, Takanobu, Kenji, Senoh, Hideki, Umeda, Yumi, Kanno, Jun
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Society of Toxicology 2020; Japan Science and Technology Agency
• Subjects: Animals; Atrophy; Butyl 2,3-epoxypropyl ether; Carcinogenesis; Carcinogenicity; Carcinogens; Carcinogens - toxicity; Carcinoma, Squamous Cell - chemically induced; Dose-Response Relationship, Drug; Epithelium; Ethers - toxicity; Exposure; Female; Females; Hyperplasia; Inhalation; Lesions; Leukemia; Leukemia - chemically induced; Male; Males; Metaplasia; Mice, Inbred Strains; Mouse; Nasal cavity; Nose; Nose Neoplasms - chemically induced; Olfactory epithelium; Rat; Rats, Inbred F344; Respiration; Respiratory tract; Rodents; Spleen; Squamous cell carcinoma; Statistical analysis; Time Factors; Uterus; Butyl 2,3-epoxypropyl ether; Nasal cavity; Mouse; Rat; Carcinogenesis; Inhalation
• ISSN: 0388-1350; 1880-3989
• DOI: 10.2131/jts.45.1

Butyl 2,3-epoxypropyl ether (CAS No. 2426-08-6, synonym: n-butylglycidyl ether, BGE) was exposed by whole body inhalation to F344 rats and BDF1 mice of both sexes (50 animals per group) 6 hours per day, 5 days per week for 104 weeks at targeted concentrations of 0, 10, 30 or 90 ppm (v/v) for rats and 0, 5, 15 or 45 ppm for mice. In rats, 90 ppm of BGE increased the incidences of nasal squamous cell carcinomas in both sexes. Nasal adenomas and splenic mononuclear cell leukemia were increased in male rats exposed to 30 ppm. Splenic mononuclear cell leukemia was increased in female rats by trend test. Non-neoplastic nasal lesions, such as squamous cell hyperplasia with atypia, squamous cell metaplasia and the inflammation of the respiratory region and atrophy of the olfactory epithelium were increased in both sexes in a dose-dependent manner. In mice, the incidences of histiocytic sarcomas of the uterus in female mice were increased in a dose-dependent manner and the incidences of nasal hemangiomas in both sexes were increased in a dose-dependent manner. Nasal squamous cell carcinoma, a rare tumor, was observed, although not statistically significant, in both sexes. Non-neoplastic lesions such as nodular hyperplasia of the transitional epithelium and cuboidal changes of the respiratory epithelium in the nasal cavity, were increased both in males and females in a dose-dependent manner. The present study demonstrated clear evidence of carcinogenicity of BGE in both rats and mice by the 2-year whole body inhalation exposure.