Inhalation carcinogenicity and toxicity of 1,2-dichloropropane in rats.
The toxicity and carcinogenicity of 1,2-dichloropropane (DCP) were examined by inhalation exposure of male and female F344 rats to DCP for either 13 wk or 2 years. In the 13-wk study, the DCP concentrations used were 125, 250, 500, 1000, or 2000 ppm (v/v), and in the 2-year study the DCP concentrations were 80, 200, or 500 ppm (v/v). Thirteen-week exposure to DCP induced hyperplasia in the respiratory epithelium and atrophy of the olfactory epithelium at 125 ppm and above. At the higher levels of exposure, hemolytic anemia and lesions of liver and adrenal gland were observed. Two-year exposure to DCP significantly increased incidences of papilloma in the nasal cavity of male and female rats exposed to 500 ppm DCP. In addition, three cases of esthesioneuroepithelioma were observed in the DCP-exposed male rats. Total nasal tumors increased in a concentration-dependent manner. Hyperplasia of the transitional epithelium and squamous cell hyperplasia, both of which were morphologically different from the hyperplasia of the respiratory epithelium observed in the 13-wk exposure study, occurred in a concentration-dependent manner; these lesions are considered to be preneoplastic lesions. Atrophy of the olfactory epithelium, inflammation of the respiratory epithelium, and squamous cell metaplasia were also seen in the 2-year study. These results demonstrate that DCP is a nasal carcinogen in rats. Lifetime cancer risks for humans exposed to DCP in the ambient air and work environment were quantitatively estimated, using both nonthreshold and threshold approaches, with the data obtained from the 2-year study.
Japan Bioassay Research Center, Japan Industrial Safety and Health Association, 2445 Hirasawa, Hadano, Kanagawa 257-0015, Japan. y-umeda@jisha.or.jp
Yumi
Y
Umeda
Michiharu
M
Matsumoto
Shigetoshi
S
Aiso
Tomoshi
T
Nishizawa
Kasuke
K
Nagano
Heihachiro
H
Arito
Shoji
S
Fukushima
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004848:Epithelium / Q000473:pathology; D005260:Female; D006965:Hyperplasia / Q000139:chemically induced; D019570:Inhalation Exposure; D008297:Male; D008679:Metaplasia / Q000139:chemically induced; D009296:Nasal Cavity / Q000473:pathology*; D009669:Nose Neoplasms / Q000139:chemically induced*; D011407:Propane / Q000031:analogs & derivatives* / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D036401:Toxicity Tests, Chronic / Q000379:methods
D002273:Carcinogens; C004765:propylene dichloride; D011407:Propane