Dose-Dependent Cytotoxicity of Chlorinated Hydrocarbons in Isolated Rat Hepatocytes. DAHLSTROM-KJNG, L., COUTURE, J., LAMOUREUX, C, VAILLANCOURT, T., AND PLAA, G. L. (1990).Fundam. Appl. Toxicol.14, 833–841. The aim was to determine if isolated suspended hepatocytes could differentiate between the effects of four chlorinated hydrocarbons that are hepatotoxicIn vivoand four that are not. Membrane integrity was assessed by measuring alanine aminotransferase (ALT) release after 30- to 180-min incubationsin vitro. From the results, the chlorinated hydrocarbons fell into three groups: tetrachloroethylene and 1,1,2,2-tetrachloroeth-ane were the most potent cytotoxicants; CCl4, 1,1,2-trichloroethane, and trichloroethylene exhibited intermediate cytotoxicity; and low cytotoxicity was observed with CHCl3, 1,1,1 -trichlo-roethane, and 1,1-dichloroethylene. Cytotoxicity ranking correlated poorly with the reportedIn vivohepatotoxicity of these agents. The effect of adding SKF-525A on the cytotoxicity of tetrachloroethylene and CCI4 was also assessed. In addition, hepatocytes from rats pretreated with 2,5-hexanedione were used to determine if they were more susceptible to the effects of CHCl3, CCl4or tetrachloroethylene. SKF-525A decreased the cytotoxicity of both CO, and tetrachloroethylene, whereas pretreatment with 2,5-hexanedione enhanced their effect. The effects of both SKF-525A and 2,5-hexanedione on CClin vitroare consistent withIn vivofindings. However, tetrachloroethylene is not hepatotoxicIn vivo, suggesting that SKF-525A might act by stabilizing plasma membranes rendering the hepatocyte more resistant to lysis. Overall, the results cast doubts on the use of ALT release from isolated hepatocytes as an appropriatein vitromodel for assessing hepatotoxic properties of chlorinated hydrocarbon