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.