Oxidation of carbon tetrachloride, bromotrichloromethane, and carbon tetrabromide by rat liver microsomes to electrophilic halogens.

In order to determine whether CCl4, CBrCl3, CBr4 or CHCl3 undergo oxidative metabolism to electrophilic halogens by liver microsomes, they were incubated with liver microsomes from phenobarbital pretreated rats in the presence of NADPH and 2,6-dimethylphenol. The analysis of the reaction mixtures by capillary gas chromatography mass spectrometry revealed that 4-chloro-2,6-dimethylphenol was a metabolite of CCl4 and CBrCl3 whereas 4-bromo-2,6-dimethylphenol was a metabolite of CBr4. The formation of the metabolites was significantly decreased when the reactions were conducted with heat denatured microsomes, in the absence of NADPH or under an atmosphere of N2. These results indicate that the chlorines of CBrCl3 and CCl4 and the bromines of CBr4 are oxidatively metabolized by rat liver microsomes to electrophilic and potentially toxic metabolites.