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In Vivo Genotoxicity and Acute Hepatotoxicity of 1,2-Dichloroethane in Mice: Comparison of Oral, Intraperitoneal, and Inhalation Routes of Exposure¹

Toxicology Research Laboratory, Department of Environmental and Industrial Health, The University of Michigan School of Public Health, Ann Arbor, Michigan 48109-2029

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 non-tumorigenic 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.

¹ Supported by NIH Grant 5 T32 ES07062.

² Present address: Merck Institute for Therapeutic Research, Building 44-1, West Point, PA 19486. To whom requests for reprints should be addressed.

Received 1/23/84. Accepted 6/25/84.

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