Bromo and chlorobiphenyl metabolism: Gas chromatographic mass spectrometric identification of urinary metabolites and the effects of structure on their rates of excretion

The identification of the hydroxylated rat urinary metabolites of the 2‐, 3‐ and 4‐chlorobiphenyls and 2‐, 3‐ and 4‐bromobiphenyls has been determined by gas chromatographic mass spectrometric analysis of their corresponding methyl ether derivatives. The electron impact fragmentation patterns of the bromomethoxybiphenyls and chloromethoxybiphenyls were used to assign the position of the methoxyl group (ortho, meta or para to the biphenyl bond); the mass spectra of the corresponding [²H₅]halobiphenyls confirmed the sites of hydroxylation by distinguishing between the halophenyl and phenyl rings. The results illustrated that ring hydroxylation occurs predominantly at the para positions of the biphenyl nucleus and at sites which are ortho and para to the halogen substituents. 4,4′‐Dimethoxyhalobiphenyls are major urinary metabolites of the 2‐ and 3‐halobiphenyls and the rapid formation of these metabolites is illustrated in a time course study which monitors the urinary metabolites formed after the separate coadministration of the isomeric chlorobiphenyl and bromobiphenyl substrates to rats.