Induction of drug-metabolizing enzymes by fractionated commercial polybrominated biphenyls (PBBs)

A commercial polybrominated biphenyl mixture was separated chromatographically into two fractions on neutral alumina (A_A and A_B) and into three fractions on Florisil (F_A, F_B, and F_C) by sequential elution with solvents of increasing polarity. Using established methods, the activity of each fraction as hepatic microsomal cytochrome P-450- and/or cytochrome P-448-dependent monooxygenase enzyme inducers was examined in the male Wister rat. Like the coadministration of phenobarbitone and 3-methylcholanthrene, commercial PBBs, either unfractionated or reconstituted from its various fractions, induced both cytochromes P-450 and P-448. Both cytochromes were also induced by the less-polar fractions A_A and F_A. In contrast, little or no inductive effects were exhibited by the more polar Florisil fractions, F_B and F_C, indicating that the ability of commercial PBBs to induce cytochrome P-448 is not due to contaminating brominated dibenzofurans or dibenzodioxins. Unlike the polar Florisil fraction, the more polar alumina fraction, A_B, was a potent microsomal enzyme inducer. This fraction was enriched in 2,3,3′,4,4′,5-hexa- and 2,2′,3,3′,4,4′,5-heptabromobiphenyl and also contained unassigned monochloro derivatives of a penta- and hexabromobiphenyl, namely C₁₂H₄Br₅Cl and C₁₂ H₃Br₆Cl, respectively. The data strongly suggest that the biologic effects of the commercial polybrominated biphenyl mixture are due to the various halogenated biphenyls present. These results are discussed in terms of the reported toxic potency of each PBB fraction and with reference to the known biologic activity of individual polybrominated biphenyl congeners or their chloro analogs.