TOXICITY OF DICHLOROPROPANOLS IN RAT HEPATOCYTE CULTURES

Exposure of humans to dichloropropanols has been shown to result in fu lminant hepatic necrosis. These compounds have also been shown to be h epatotoxic in rats. In this study, 1,3-dichloropropanol, but not 2,3-d ichloropropanol, was shown to be toxic to 24 h cultures of rat hepatoc ytes. The toxicity was inhibited by pre-treatment of cultures with a c ytochrome P450 inhibitor and enhanced by prior depletion of cellular g lutathione. In addition, at equimolar concentrations both isomers were shown to deplete glutathione, although the extent of depletion was gr eater with the 1,3-isomer. 1,3-Dichloropropanol also depleted ATP and reduced the mitochondrial membrane potential. The effects on ATP, glut athione and membrane potential could be inhibited by the cytochrome P4 50 inhibitor. It is concluded that the toxicity of 1,3-dichloropropano l is mediated by cytochrome P450 and involves depletion of glutathione and loss of mitochondrial function.