Oxidative metabolism of BDE 47, BDE 99, and HBCDs by cat liver microsomes: Implications of cats as sentinel species to monitor human exposure to environmental pollutants.
The in vitro oxidative metabolism of 2,2',4,4' tetrabromodiphenyl ether (BDE 47) 2,2',4,4',5 pentabromodiphenyl ether (BDE 99) and individual a b and g hexabromocyclododecane (HBCD) isomers catalyzed by cytochrome P450 (CYP) enzymes was screened using cat liver microsomes (CLMs) Six hydroxylated metabolites, namely 4 hydroxy 2,2',3,4' tetrabromodiphenyl ether (4 OH BDE 42) 3 hydroxy 2,2',4,4' tetrabromodiphenyl ether (3 OH BDE 47) 5 hydroxy 2,2',4,4' tetrabromodiphenyl ether (5 OH BDE 47) 6 hydroxy 2,2',4,4' tetrabromodiphenyl ether (6 OH BDE 47) 4' hydroxy 2,2',4,5' tetrabromodiphenyl ether (4' OH BDE 49) and 2' hydroxy 2,3',4,4' tetrabromodiphenyl ether (2' OH BDE 66) were identified and quantified after incubation of BDE 47. A di OH tetra BDE was also found as metabolite of BDE 47 with CLMs. 5 OH BDE 47 was the major metabolite formed. Five hydroxylated metabolites (3' hydroxy 2,2',4,4',5 pentabromodiphenyl ether (3' OH BDE 99) 5' hydroxy 2,2',4,4',5 pentabromodiphenyl ether (5' OH BDE 99) 6 hydroxy 2,2',4,4',5 pentabromodiphenyl ether (6 OH BDE 99) 6' hydroxy 2,2',4,4',5 pentabromodiphenyl ether (6' OH BDE 99) and 4' hydroxy 2,2',4,5,5' pentabromodiphenyl ether (4' OH BDE 101) were formed from BDE 99 incubated with CLMs. Concentrations of BDE 99 metabolites were lower than those of BDE 47. Four or more mono hydroxylated HBCD (OH HBCDs) four or more di hydroxylated HBCD (di OH HBCDs) five or more mono hydroxylated pentabromocyclododecanes (OH PBCDs) and five or more di hydroxylated pentabromocyclododecenes (di OH PBCDs) were detected after incubation of a b or g HBCD with CLMs. No diastereoisomeric or enantiomeric enzymatic isomerisation was observed incubating a b or g HBCD with CLMs. Collectively, our data suggest that (i) BDE 47 is metabolized at a faster rate than BDE 99 by CLMs, (ii) OH HBCDs are the major hydroxylated metabolites of a b and g HBCD produced by CLMs, and (iii) the oxidative metabolism of BDE 47 and BDE 99 is different by cat and human liver microsomes. This suggests that cats are not a suitable sentinel to represent internal exposure of PBDEs for humans, but is likely a promising sentinel for internal HBCDs exposure for humans.
Chemosphere