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2,2',3,5',6-Pentachlorobiphenyl (PCB 95) Is Atropselectively Metabolized to para-Hydroxylated Metabolites by Human
Eric Uwimana1, Xueshu Li1, Hans-Joachim Lehmler1
1Interdisciplinary Graduate Program in Human Toxicology and Department of Occupational and Environmental Health, University of Iowa , Iowa City, Iowa 52242, United States.
Abstract:
Exposure to neurotoxic, chiral PCBs has been associated with neurodevelopmental disorders, but their metabolism in humans remains unexplored. We investigated the enantioselective metabolism of PCB 95 by human liver microsomes (HLMs) to potentially neurotoxic, hydroxylated metabolites (OH-PCBs). OH-PCB profiles formed in experiments with HLMs differed from metabolite profiles reported for rodent species. The second eluting atropisomer of 2,2',3,5',6-pentachlorobiphenyl-4'-ol, the major metabolite, was preferentially formed by all HLM preparations investigated. Differences in metabolite formation rates were observed with single donor HLMs. The metabolism of PCBs and its role in PCB-mediated neurodevelopmental disorders need to be further characterized.
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