Rapid halogenated hydrocarbon toxicity in isolated hepatocytes is mediated by direct solvent effects.

The toxicity of several halogenated and non-halogenated hydrocarbons (CH2Cl2, CHCl3, CCl4, C6H14, C8H10) in isolated rat hepatocytes were compared. Release of aspartate aminotransferase (AST) activity was rapid and concentration-dependent. Fractional AST release plateaued at 10-60 min following hydrocarbon exposure. Enzyme leakage at 60 min correlated with the oil/water partition coefficient (pi) of the compounds. All compounds, except n-hexane, also caused an immediate inhibition of the rate of cellular respiration. Inhibition of cell respiration also correlated with pi and was reversible. The recovery of cellular oxygen consumption was examined in detail for CCl4 and correlated with evaporation of the compound. These data suggest that acute hydrocarbon-induced injury in isolated hepatocytes is mediated by concentration-dependent direct solvent effects. Since halogenated hydrocarbons are widely used to induce general anesthesia, the clinical implications of possible direct effects by halocarbons on liver function in vivo and the potential relationship to liver injury are discussed.