Primary Role of Cytochrome P450 2B6 in the Oxidative Metabolism of 2,2′,4,4′,6-Pentabromodiphenyl Ether (BDE-100) to Hydroxylated BDEs

Human exposure to polybrominated diphenyl ethers (PBDEs) through various routes poses deleterious health effects. PBDEs are biotransformed into hydroxylated metabolites (OH-BDEs) via cytochrome P450s (P450s), which may add to their neurotoxic effects. This study characterizes the in vitro metabolism of 2,2′,4,4′,6-pentabromodiphenyl ether (BDE-100), one of the most abundant PBDE congeners found in humans, by recombinant human P450s and pooled human liver microsomes (HLMs). Ten recombinant P450s were individually incubated with BDE-100 to monitor P450-specific metabolism. P450 2B6 was found to be the predominant enzyme responsible for nearly all formation of six mono-OH-pentaBDE and two di-OH-pentaBDE metabolites. Four metabolites were identified as 3-hydroxy-2,2′,4,4′,6-pentabromodiphenyl ether (3-OH-BDE-100), 5′-hydroxy-2,2′,4,4′,6-pentabromodiphenyl ether (5′-OH-BDE-100), 6′-hydroxy-2,2′,4,4′,6-pentabromodiphenyl ether (6′-OH-BDE-100), and 4′-hydroxy-2,2′,4,5′,6-pentabromodiphenyl ether (4′-OH-BDE-103) ...