TY - JOUR
T1 - Enantioselective biotransformation of hexabromocyclododecane by in vitro rat and trout hepatic sub-cellular fractions
AU - Abdallah, Mohamed Abou-Elwafa
AU - Uchea, Chibuzor
AU - Chipman, J Kevin
AU - Harrad, Stuart
PY - 2014/3/4
Y1 - 2014/3/4
N2 - 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.
AB - 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.
U2 - 10.1021/es404644s
DO - 10.1021/es404644s
M3 - Article
C2 - 24483621
SN - 0013-936X
VL - 48
SP - 2732
EP - 2740
JO - Environmental Science & Technology
JF - Environmental Science & Technology
IS - 5
ER -