Microsomal Oxidation of 2,2′,3,3′,6,6′-Hexachlorobiphenyl (PCB 136) Results in Species-Dependent Chiral Signatures of the Hydroxylated Metabolites

Chiral polychlorinated biphenyls (PCBs) display variable atropisomeric enrichment in wildlife and animal models, especially at higher trophic levels. These differences in PCBs' chiral signatures are, at least in part, due to species-dependent oxidation of PCBs to hydroxylated PCB metabolites (OH-PCBs). Here, we investigate the hypothesis that the cytochrome P450 (P450) enzyme-mediated oxidation of chiral PCBs results in species-dependent differences in the chiral signatures of OH-PCBs (i.e., the direction and extent of OH-PCBs' atropisomeric enrichment). To investigate this hypothesis, we incubated PCB 136, a representative chiral PCB, with pooled human liver microsomes (HLMs) or liver microsomes from male guinea pig, hamster, monkey, mouse, and rabbit or female dog and determined average profiles and chiral signatures of the OH-PCBs. 2,2',3,3',6,6'-Hexachlorobiphenyl-4-ol (4-136) was the major metabolite in incubations with HLMs and monkey and rabbit microsomes. 2,2',3,3',6,6'-Hexachlorobiphenyl-5-ol (5-136) was the major metabolite formed by microsomes from all other species. Both 4-136 and 5-136 were formed atropselectively in all microsomal incubations; however, the direction and extent of the atropisomeric enrichment of both OH-PCB metabolites showed considerable differences across microsomal preparations obtained from different species. These differences in OH-PCBs' atropisomeric enrichment may not only be toxicologically relevant but may also be useful to study sources and transport of OH-PCBs in the environment.