Carcinogenicity and chronic toxicity in rats and mice exposed by inhalation to 1,2-dichloroethane for two years.
Carcinogenicity and chronic toxicity of 1,2-dichloroethane (DCE) were examined by inhalation exposure of groups of 50 F344 rats and 50 BDF1 mice of both sexes to DCE vapor or clean air as control for 6 h/d, 5 d/wk and 104 wk. The rats were exposed to 10, 40 or 160 ppm (v/v) DCE, while the mice were exposed to 10, 30 or 90 ppm. The 2-yr exposure to DCE produced a dose-dependent increase in incidences of benign and malignant tumors, including subcutaneous fibroma, mammary gland fibroadenoma and peritoneal mesothelioma in male rats; subcutaneous fibroma and mammary gland adenoma, fibroadenoma and adenocarcinoma in female rats; and bronchiolo-alveolar adenoma and carcinoma, endometrial stromal polyp, mammary gland adenocarcinoma and hepatocellular adenoma in female mice. No exposure-related change in the incidence of non-neoplastic lesions or in any hematological, blood biochemical or urinary parameter occurred in any DCE-exposed rat or mouse group. The types of tumors and their target organs found in this study were consistent with those observed in rats and mice administered DCE by gavage in a NCI study. Selection of the exposure concentrations was considered appropriate with reference to the maximum tolerated dose for the highest doses and an occupational exposure limit of DCE for the lowest dose. The present findings suggest that those carcinogenic responses be primarily considered for standard setting of occupational and environmental exposure to DCE.
Nagano
Kasuke
K
Japan Bioassay Research Center, Japan Industrial Safety and Health Association, Kanagawa, Japan. k-nagano@jisha.or.jp
Umeda
Yumi
Y
Senoh
Hideki
H
Gotoh
Kaoru
K
Arito
Heihachiro
H
Yamamoto
Seigo
S
Matsushima
Taijiro
T
D000818:Animals; D015197:Carcinogenicity Tests / Q000379:methods; D002273:Carcinogens / Q000633:toxicity*; D005025:Ethylene Dichlorides / Q000633:toxicity*; D005260:Female; D019570:Inhalation Exposure / Q000009:adverse effects*; D008297:Male; D020714:Maximum Tolerated Dose; D051379:Mice; D023421:Models, Animal; D009369:Neoplasms / Q000139:chemically induced; D016273:Occupational Exposure / Q000009:adverse effects*; D051381:Rats; D011916:Rats, Inbred F344; D016019:Survival Analysis; D036401:Toxicity Tests, Chronic
D002273:Carcinogens; D005025:Ethylene Dichlorides; C024565:ethylene dichloride