In vivo genotoxicity and acute hepatotoxicity of 1,2-dichloroethane in mice: comparison of oral, intraperitoneal, and inhalation routes of exposure.
The in vivo genotoxicity of 1,2-dichloroethane (DCE) was studied in the liver of male C57BL/6 X C3H F1 (hereafter called B6C3F1) mice after single p.o., i.p., and inhalation exposures. The acute hepatotoxicity of DCE was also examined in order to determine nonnecrogenic exposure levels for each route of administration. Single-strand breaks and/or alkali-labile lesions were demonstrated by alkaline DNA-unwinding/hydroxylapatite chromatography in hepatic DNA at 4 hr after p.o. or i.p. administration of nonnecrogenic doses (100 mg/kg, p.o.; 150 mg/kg, i.p.) of DCE to groups of four to six mice. No evidence of hepatic DNA damage was found immediately following 4-hr inhalation exposures of mice to a nonnecrogenic (150 ppm) or necrogenic (500 ppm) concentration of DCE. Four-hr inhalation exposures of mice to concentrations of DCE causing high mortality within 24 hr (1000 to 2000 ppm) produced evidence of hepatic DNA damage at 4 hr, but the possibility that this damage was due to the acute necrogenic effects of the exposures could not be excluded. A significant fraction of the hepatic DNA damage observed 4 hr after i.p. administration of DCE (200 mg/kg) was still evident after 24 hr, indicating the persistence of unrepaired lesions in the DNA. These findings are consistent with the seemingly contradictory results of the two long-term carcinogenicity bioassays, in which DCE was found to be carcinogenic to Osborne-Mendel rats and B6C3F1, mice when administered by gavage but nontumorigenic to Sprague-Dawley rats and Swiss mice after chronic inhalation exposure. Therefore, our results provide additional evidence for the importance of a route of administration effect in the in vivo genotoxicity and carcinogenicity of DCE.
D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005025:Ethylene Dichlorides / Q000008:administration & dosage / Q000633:toxicity*; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000033:anatomy & histology / Q000187:drug effects; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects
D005025:Ethylene Dichlorides; D006843:Hydrocarbons, Chlorinated; C024565:ethylene dichloride