Enantioselective biotransformation of hexabromocyclododecane by in vitro rat and trout hepatic sub-cellular fractions.
α-, β-, and γ-Hexabromocyclododecanes (HBCDs) were subjected to in vitro biotransformation experiments with rat and trout liver S9 fractions for different incubation times (10, 30, and 60 min) at 2 concentration levels (1 and 10 μM). The metabolic degradation of target HBCDs followed first order kinetics. Whereas β-HBCD undergoes rapid biotransformation (t0.5 = 6.4 and 38.1 min in rat and trout, respectively), α-HBCD appears the most resistant to metabolic degradation (t0.5 = 17.1 and 134.9 min). The biotransformation rate in trout was slower than in rat. Investigation of HBCD degradation profiles revealed the presence of at least 3 pentabromocyclododecene (PBCD) and 2 tetrabromocyclododecadiene (TBCD) isomers indicating reductive debromination as a metabolic pathway for HBCDs. Both mono- and di- hydroxyl metabolites were identified for parent HBCDs, while only mono hydroxyl metabolites were detected for PBCDs and TBCDs. Interestingly, δ-HBCD was detected only in trout S9 fraction assays indicating metabolic interconversion of test HBCD diastereomers during biotransformation in trout. Finally, enantioselective analysis showed significant enrichment of the (-)-α-HBCD enantiomer (EF = 0.321 and 0.419 after 60 min incubation in rat and trout, respectively). The greater enrichment of (-)-α-HBCD in rat than in trout underlines the species-specific differences in HBCD metabolism and the need for caution when extending similar results from animal studies to humans.
Division of Environmental Health and Risk Management, School of Geography, Earth and Environmental Sciences, University of Birmingham , Birmingham, B15 2TT, United Kingdom.
Mohamed Abou-Elwafa
MA
Abdallah
Chibuzor
C
Uchea
J Kevin
JK
Chipman
Stuart
S
Harrad
D000818:Animals; D001711:Biotransformation; D006842:Hydrocarbons, Brominated / Q000737:chemistry / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017686:Oncorhynchus mykiss; D051381:Rats; D013045:Species Specificity; D013237:Stereoisomerism; D013347:Subcellular Fractions / Q000378:metabolism
D006842:Hydrocarbons, Brominated; C521198:pentabromocyclododecene; C089796:hexabromocyclododecane