Alpha and beta isomers of tetrabromoethylcyclohexane (TBECH) flame retardant: depletion and metabolite formation in vitro using a model rat microsomal assay.
The metabolism of α- and β-isomers of the flame retardant chemical tetrabromoethylcyclohexane (TBECH) was investigated using a model in vitro enzyme-mediated biotransformation assay based on rat liver microsomes. In enzymatically active assays, concentrations of both α- and β-TBECH isomers were equally depleted by about 40% and in a time-dependent fashion over a 60-min assay incubation period, and determined by GC-MS(ECNI) analysis. No such depletion was observed in nonenzymatically active control assays. After the full 60-min assay incubation period, debrominated TBECH metabolites were not detected by GC-MS(ECNI), and suggested that enzyme-mediated debromination of TBECH did not occur via cyctochrome P450 enzyme-mediated catalysis or that the rate of TBECH metabolism in vitro was too slow. In the enzymatically active assays, but not in the nonezymatically active control assays, α- and β-monohydroxy-TBECH (OH-TBECH), dihydroxy-TBECH ((OH)(2)-TBECH), and some additional compounds with molecular formulas of C(8)H(13)Br(3)O(2) and C(8)H(11)Br(3)O(2) were identified by LC-Q-ToF-MS. Two unique sets of OH-TBECH and (OH)(2)-TBECH metabolites were derived from both α- and β-TBECH isomers. The LC-ESI(-)-MS/MS peak areas of all four OH-TBECH and (OH)(2)-TBECH metabolites increased at a comparable rate in a time-dependent manner over a 60-min assay incubation period. This study demonstrated that metabolism via hydroxylation can occur in vitro for α- and β-TBECH. These results underscore the importance of understanding the biological fate of TBECH and the possible implications on the health and TBECH levels in exposed wildlife and in the environment.
Ecotoxicology and Wildlife Health Division, Science and Technology Branch, Environment Canada, National Wildlife Research Centre (NWRC), Ottawa, ON, Canada.
Shaogang
S
Chu
Lewis T
LT
Gauthier
Robert J
RJ
Letcher
D000818:Animals; D003510:Cyclohexanes / Q000032:analysis / Q000378:metabolism*; D004785:Environmental Pollutants / Q000032:analysis / Q000378:metabolism*; D005411:Flame Retardants / Q000032:analysis / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D007536:Isomerism; D008862:Microsomes, Liver / Q000378:metabolism*; D008958:Models, Molecular; D051381:Rats; D053719:Tandem Mass Spectrometry
D003510:Cyclohexanes; D004785:Environmental Pollutants; D005411:Flame Retardants; C517232:1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane