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Title
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In vitro metabolism of BDE-47, BDE-99, and -, -, -HBCD isomers by chicken liver microsomes
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Author
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Abstract
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| The in vitro oxidative metabolism of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), 2,2',4,4',5-pentabromodiphenyl ether (BDE-99), and the individual alpha-, beta- and gamma-hexabromocyclododecane (HBCD) isomers catalyzed by cytochrome P450 (CYP) enzymes was studied using chicken liver microsomes (CLMs). Metabolites were identified using a liquid chromatography-tandem mass spectrometry method and authentic standards for the oxidative metabolites of BDE-47 and BDE-99. Six hydroxylated tetra-BDEs, 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 with CLMs. 4'-OH-BDE-49 was the major metabolite formed. Three hydroxylated penta-BDEs (5'-hydroxy-2,2',4,4',5-pentabromodiphenyl ether (5'-OH-BDE99), 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 incubating BDE-99 with CLMs. Concentrations of BDE-99 metabolites were lower than those of BDE-47. More than four mono-hydroxylated HBCD (OH-HBCD), more than four di-hydroxylated HBCD (di-OH-HBCD), more than five mono-hydroxylated pentabromocyclododecenes (OH-PBCD), and more than five di-hydroxylated pentabromocyclododecenes (di-OH-PBCD) were detected when alpha-, beta-, or gamma-HBCD were individually incubated with CLMs. Response values (the ratio between the peak areas of the target compound and its internal standard) for OH-HBCD were 1-3 orders of magnitude higher than those for OH-PBCD, di-OH-HBCD, and di-OH-PBCD, suggesting that OH-HBCD might be the major metabolites of alpha-, beta- and gamma-HBCD produced by CLMs. No diastereoisomeric or enantiomeric bioisomerisation was observed incubating alpha-, beta- or gamma-HBCD with CLMs. Collectively, our data suggest that (i) BDE-47 is metabolized at a faster rate than BDE-99 by CLMs, (ii) OHHBCD are the major hydroxylated metabolites of alpha-, beta- and gamma-HBCD produced by CLMs and (iii) the diastereoisomeric or enantiomeric bioisomerisation of alpha-, beta- and gamma-HBCD is not mediated by chicken CYP enzymes. (C) 2015 Elsevier Inc. All rights reserved. |
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Language
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English
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Source (journal)
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Environmental research. - Amsterdam, 1967, currens
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Publication
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Amsterdam
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Elsevier
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2015
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ISSN
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0013-9351
[print]
1096-0953
[online]
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DOI
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10.1016/J.ENVRES.2015.10.023
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Volume/pages
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143
:A
(2015)
, p. 221-228
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ISI
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000365831400028
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Pubmed ID
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26505652
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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