Dose-related hepatotoxicity of 1,1,2-trichloro-1,2,2-trifluoroethane in short-term intermittent inhalation exposure in rats.
Male Wistar rats were exposed to 200, 1000 or 2000 ppm of 1,1,2-trichloro-1,2,2-trifluoroethane vapor 5 days a week 6 h daily for 1 or 2 weeks. Proliferation and vacuolisation of the smooth endoplasmic reticulum (SER) of the liver was seen electron microscopically after 1 and 2 weeks in the rats exposed to 1000 and 2000 ppm. Among the hepatic drug metabolizing enzymes, NADPH cytochrome c reductase activity showed a dose-related decrease whereas the tightly membrane-bound UDPglucuronosyltransferase exhibited a dose-dependent enhancement in its measurable activity. The overall drug oxidation reaction, 7-ethoxycoumarin O-deethylase was not affected by the 1,1,2-trichloro-1,2,2,-trifluoroethane inhalation at all, either in the liver or in the kidneys. 1,1,2-Trichloro-1,2,2-trifluoroethane binds to cytochrome P-450 with the production of a type I difference spectrum, suggesting that it may act as a substrate for this enzyme. The binding affinity is increased by phenobarbital-treatment of the rats.
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000473:pathology; D064227:Chlorofluorocarbons, Ethane; D005617:Chlorofluorocarbons, Methane / Q000008:administration & dosage / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005740:Gases; D008099:Liver / Q000201:enzymology; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism; D051381:Rats
D064227:Chlorofluorocarbons, Ethane; D005617:Chlorofluorocarbons, Methane; D005740:Gases; D004364:Pharmaceutical Preparations; C007786:1,1,2-trichloro-1,2,2-trifluoroethane; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases