Toxicity of mixtures of trichloroethylene, tetrachloroethylene and 1,1,1-trichloroethane: similarity of in vitro to in vivo responses.
The toxicities of various combinations of trichloroethylene (TRI), tetrachloroethylene (TET) and 1,1,1-trichloroethane (TCE) were examined in suspensions of rat hepatocytes and in vivo. For each pair and for the three solvents together, an interactive toxicity was demonstrated in vitro, as determined by release of potassium ion and cytoplasmic enzymes. A similar pattern of response was found after administration to the intact rat for increases in plasma alanine aminotransferase and sorbitol dehydrogenase, both indices of hepatotoxicity. Plasma urea levels were significantly elevated on exposure to the three chemicals together. Thus a remarkably similar pattern of toxicity was found in vitro and in vivo, which supports the possible use of hepatocyte suspensions as a screening procedure for toxicity of mixtures.
National Institute of Occupational Health and Safety, University of Sydney, Australia.
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Stacey
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000209:etiology* / Q000378:metabolism; D004338:Drug Combinations; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D066298:In Vitro Techniques; D007064:L-Iditol 2-Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013750:Tetrachloroethylene / Q000633:toxicity*; D014240:Trichloroethanes / Q000633:toxicity*; D014241:Trichloroethylene / Q000633:toxicity*
D004338:Drug Combinations; D006843:Hydrocarbons, Chlorinated; D014240:Trichloroethanes; C024566:1,1,1-trichloroethane; D014241:Trichloroethylene; D007064:L-Iditol 2-Dehydrogenase; D000410:Alanine Transaminase; D013750:Tetrachloroethylene