The Mechanism of Chlorobiphenyl Metabolism

4-Chlorobiphenyl was administered to rabbits and the major urinary metabolites were identified as 4′-chloro-4-biphenylol and 4′-chloro-3,4-biphenyldiol. It was also shown that 4′-chloro-4-biphenylol was also converted into the diol as well as its monomethyl derivatives. The biohydroxylation pathway was further investigated using 4′-[²H]-4-chlorobiphenyl as a substrate. The 4′-chloro-4-biphenylol metabolite retained 79% of the deuterium and the results are consistent with the intermediacy of an arene oxide in the first hydroxylation reaction. The diol metabolite retained ca. one-half the deuterium found in the phenol (39%) and it is therefore not formed directly from the arene oxide but by direct hydroxylation of the phenolic metabolite. The sequence of hydroxylation of chlorobiphenyl is, therefore, analogous to the stepwise hydroxylation of phenylalanine to give 3,4-dihydroxyphenylalanine and butamoxane to give 6,7-dihydroxybutamoxane.