Biotransformation of the Flame Retardant 1,2-Dibromo-4-(1,2-dibromoethyl)cyclohexane (TBECH) in Vitro by Human Liver Microsomes

• DOI: 10.1021/acs.est.7b02834
• Publication Date: 2017-08-28T16:52:50Z
• Authors: Khanh-Hoang Nguyen; Mohamed Abou-Elwa...; Thomas Moehring; Stuart Harrad
• Keywords: Biotransformation; Hydroxylation

The technical mixture of 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (TBECH or DBE-DBCH) and the pure β-TBECH isomer were subjected to in vitro biotransformation by human liver microsomes (HLM). After 60 min incubation, 5 potential metabolites TBECH identified microsomal assays both using ultraperformance liquid chromatography-Q-Exactive Orbitrap mass spectrometry. These include mono- dihydroxylated TriBECH as well an α-oxidation metabolite bromo-(1,2-dibromocyclohexyl)-acetic acid. Our results indicate hepatic via cyctochrome P450-catalyzed hydroxylation, debromination, α-oxidation. Kinetic studies revealed that formation monohydroxy-TBECH, dihydroxy-TBECH, monohydroxy-TriBECH best fitted a Michaelis-Menten enzyme kinetic model. Respective estimated Vmax values (maximum metabolic rate) for these 11.8 ± 4, 0.6 0.1, 10.1 0.8 pmol min-1 mg protein-1 4992 1340, 14.1 4.9, 66.1 7.3 β-TBECH. This indicates monohydroxy-TBECH major HLM-based assay. intrinsic clearance (Clint) was slower (P < 0.05) than While may reduce bioaccumulation provide useful biomarker monitoring exposure, further are required fully understand levels toxicological implications metabolites.