Hepatotoxic interaction between carbon tetrachloride and chloroform in ethanol treated rats

The effect of coadministration of CHCl3 on CCl4-induced hepatic damage was investigated at low dose inhalation. Coexposure of CHCl3 did not influence CCl4-induced changes in any index of hepatic damage in control rats. Coadministration of CHCl3, however, enhanced CCl4 (10 ppm)-induced hepatic damage of ethanol treated rats in a dose- and duration-dependent manner: simultaneous exposure of 50 ppm CHCl3 potentiated CCl4-induced increase in plasma GPT activity and number of necrotic hepatocytes; the enhancement of CCl4-induced hepatic damage by 50 ppm CHCl3 was found over the 4 h exposure; simultaneous exposure of 10 and 25 ppm CHCl3 potentiated the CCl4-induced increase in liver malondialdehyde (MDA) content. In contrast, coadministration of 50 ppm trichloroethylene and 200 ppm 1,1,1-trichloroethane decreased CCl4-induced increase in plasma GPT activity, though these exposures did not influence the liver MDA content. These results suggest that the concentration of 10 ppm CCl4 may be significant for CHCl3 to potentiate the hepatic damage caused by CCl4 in ethanol-treated rats. Heavy drinkers may have a higher hepatotoxic risk for a mixture of CCl4 and CHCl3 than for a single exposure to CCl4 or CHCl3, and a particular attention should be therefore given to the joint exposure to CCl4 and CHCl3.