Previous studies have suggested that polybrominated diphenyl ethers (PBDEs) are biotransformed into hydroxylated metabolites via cytochrome P450s (CYPs), and that bioactivation through oxidative metabolism may add considerably to the neurotoxic potential of PBDEs. The purpose of this study was to characterize the in vitro metabolism of BDE-47 and BDE-100 by recombinant human cytochrome P450s (recombinant CYP2B6) and pooled human liver microsomes. Analysis was completed by gas chromatography-mass spectrometry after methylation of hydroxylated-BDE metabolites (OH-BDEs). Formation of six mono-OH-BDE and two di-OH-BDE metabolites were observed for each BDE tested. The identities of some metabolites were confirmed using available authentic standards, while others were deduced from the mass spectrometric fragmentation characteristics of methoxylated-BDEs (MeO-BDEs) combined with a computational model for the qualitative prediction of their chromatographic retention times. CYP2B6 transformed BDE-47 to 3-OH-BDE-47, 5-OH-BDE-47, 6-OH-BDE-47, 4-OH-BDE-42, 4�-OH-BDE-49, and 2�-OH-BDE-66. Similarly, BDE-100 was transformed to 3-OH-BDE-100, 4'-OH-BDE-103, 5'-OH-BDE-100, 6'-OH-BDE-100, and two di-OH-BDE metabolites.

Identification of metabolites produced during oxidative metabolism of PBDEs by human liver microsomes and cytochrome P450s

248th National Meeting (2014)

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