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.