Respiratory tract lesions in F344/N rats and B6C3F1 mice after inhalation exposure to 1,2-epoxybutane.
1,2-Epoxybutane, a short-chain epoxide used as a stabilizer in chlorinated hydrocarbon solvents, was administered by inhalation exposure as a vapor 6 h/day, 5 day/week, for 24 months at exposure concentrations of 0, 200 or 400 ppm to F344/N rats and 0, 50, or 100 ppm to B6C3F1 mice. Survival of all groups of rats was 50% or greater until week 98 but was reduced in exposed groups by the end of the study. Survival in male mice was comparable among groups. Survival in female mice was greater than 50% until week 86, but was then reduced in the high-exposure group of mice. Exposure-related inflammatory, degenerative, and proliferative lesions occurred in the nasal cavity of both rats and mice. Seven papillary adenomas occurred in the nasal passages of high-exposure male rats and 2 in the nasal passages of high-exposure female rats. Alveolar/bronchiolar adenoma or carcinoma (combined) occurred with increased incidence in exposed male rats relative to controls. No exposure-related neoplastic lesions were seen in mice. After inhalation exposure, 1,2-epoxybutane was carcinogenic in rodents as were other epoxides or related compounds including propylene oxide, 1,3-butadiene, and ethylene oxide. The site of carcinogenic activity was considered to be related to length of the carbon chain.
Dunnick
J K
JK
National Institute of Environmental Health Sciences, National Toxicology Program, Research Triangle Park, NC 27709.
Eustis
S L
SL
Piegorsch
W W
WW
Miller
R A
RA
D000280:Administration, Inhalation; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens; D004852:Epoxy Compounds / Q000633:toxicity*; D004988:Ethers, Cyclic / Q000633:toxicity*; D005260:Female; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D051379:Mice; D009297:Nasal Mucosa / Q000187:drug effects / Q000473:pathology; D009668:Nose Diseases / Q000139:chemically induced* / Q000473:pathology; D009669:Nose Neoplasms / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D012737:Sex Factors; D013045:Species Specificity
D002273:Carcinogens; D004852:Epoxy Compounds; D004988:Ethers, Cyclic; C027488:1,2-epoxybutane