期刊
ENVIRONMENTAL SCIENCE & TECHNOLOGY
卷 51, 期 18, 页码 10511-10518出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.est.7b02834
关键词
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资金
- European Union Seventh Framework Programme [606857]
The technical mixture of 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (TBECH or DBE-DBCH) and the pure beta-TBECH isomer were subjected to in vitro biotransformation by human liver microsomes (HLM). After 60 min of incubation, 5 potential metabolites of TBECH were identified in microsomal assays of both the TBECH mixture and beta-TBECH using ultraperformance liquid chromatography-Q Exactive Orbitrap mass spectrometry. These include mono- and dihydroxylated TBECH and mono- and dihydroxylated TriBECH as well as an alpha-oxidation metabolite bromo. (1,2-dibromocyclohexyl)-acetic acid. Our results indicate potential hepatic biotransfonnalion of TBECH via cyctochroine P450-catalyzed hydroxylation, debromination, and alpha-oxidation. Kinetic studies revealed that the formation of monohydroxy-TBECH, dihydroxy-TBECH, and monohydroxy-TriBECH were best fitted to a Michaelis-Menten enzyme kinetic model. Respective estimated V-max values (maximum metabolic rate) for these metabolites were 11.8 +/- 4,0.6 +/- 0.1, and 10.1 +/- 0.8 pmol min(-1) mg protein(-1) in TBECH mixture and 4992 +/- 1340, 14.1 +/- 4.9, and 66.1 +/- 7.3 pmol min' mg protein(-1) in beta-TBECH. This indicates monohydroxy-TBECH as the major metabolite of TBECH by in vitro HLM-based assay. The estimated in vitro intrinsic clearance (Cl-int) of TBECH mixture was slower (P < 0.05) than that of pure beta-TBECH. While the formation of monohydroxy-TBECH may reduce the bioaccumulation potential and provide a useful biomarker for monitoring TBECH exposure, further studies are required to fully understand the levels and toxicological implications of the identified metabolites.
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