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Human hydroxylated metabolites of BDE-47 and BDE-99 are glucuronidated and sulfated in vitro
Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
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Number of Authors: 6
2015 (English)In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 236, no 2, 98-109 p.Article in journal (Refereed) Published
Abstract [en]

Polybrominated diphenyl ethers (PBDEs) were used worldwide as additive flame retardants and are classified as persistent, bioaccumulable and toxic environmental pollutants. In humans, the hydroxylated metabolites of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and 2,2',4,4',5-pentabromodiphenyl ether (BDE-99) formed in vitro have also been detected in vivo. To further characterize the metabolism of BDE-47 and BDE-99 and to identify candidate markers for monitoring the human exposure to PBDEs using non-invasive approaches, glucuronidation and sulfation of hydroxylated metabolites of BDE-47 and BDE-99 were investigated using human liver microsomes and cytoplasm, respectively. The formed Phase II metabolites were analyzed by liquid chromatography-tandem mass spectrometry using a novel approach to develop analytical methods in absence of authentic standards. All available standards for hydroxylated metabolites of BDE-47 and BDE-99 were glucuronidated and sulfated, showing that glucuronidation and sulfation are part of the metabolism pathway of BDE-47 and BDE-99 in vitro. The major glucuronidated and sulfated analogs of hydroxylated metabolites of BDE-47 were (a) 2,4-DBP-Gluc and 5-Gluc-BDE-47, and (b) 2'-Sulf-BDE-28, 4-Sulf-BDE-42 and 3-Sulf-BDE-47, respectively. The major glucuronidated and sulfated analogs of hydroxylated metabolites of BDE-99 were (a) 2,4,5-TBP-Gluc and 6'-Gluc-BDE-99, and (b) 3'-Sulf-BDE-99 and 5'-Sulf-BDE-99, respectively. Apparent K-m values associated with the formation of sulfated metabolites of BDE-47 and BDE-99 were ten times lower than those of the corresponding glucuronidated metabolites, suggesting that sulfated rather than glucuronidated metabolites of OH-PBDEs might be used as markers of human exposure to PBDEs using a non-invasive approach based on urine sample collection.

Place, publisher, year, edition, pages
2015. Vol. 236, no 2, 98-109 p.
Keyword [en]
BDE-47, BDE-99, Glucuronidated and sulfated metabolites, In vitro, UGTs, SULTs
National Category
Chemical Sciences Basic Medicine
Identifiers
URN: urn:nbn:se:su:diva-119120DOI: 10.1016/j.toxlet.2015.05.003ISI: 000355683700004OAI: oai:DiVA.org:su-119120DiVA: diva2:843816
Available from: 2015-07-31 Created: 2015-07-29 Last updated: 2017-12-04Bibliographically approved

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