Metabolism of bromobiphenyls

The metabolism in vivo of 2-, 3- and 4-bromobiphenyl in the rabbit gave a series of mono and dihydroxylated metabolic products. The nuclear magnetic resonance spectra of the two major 4-bromobiphenyl metabolites confirmed their structures as 4′-bromo-4-biphenylol and 4′-bromo-3,4-biphenyldiol. The metabolism of 4′[²H]4-bromobiphenyl gave the corresponding monohydroxy compound in which 61 per cent of the deuterium had been retained whereas the deuterium content of the catechol was 19 per cent. The NIH shift of deuterium is consistent with metabolism via an arene oxide which rearranges to the phenol and undergoes hydration/dehydrogenation to give the catechol. The retention of 19 per cent of the deuterium in the catechol also indicated that some of the diol is formed via direct hydroxylation, as observed in the metabolism of 4-chlorobiphenyl. The metabolism in vitro of [³H]4-bromobiphenyl with hepatic microsomes gives polar metabolic products and the radioactivity is also incorporated into the protein component of the microsomal fraction. 4-Bromobiphenyl is highly mutagenic to the Salmonella typhimurium TA 1538 mutant and metabolic activation with a liver microsomal enzyme fraction is required for this activity.