title: Measurement of polybrominated diphenyl ethers and metabolites in mouse plasma after exposure to a commercial pentabromodiphenyl ether mixture.
abstract: BACKGROUND
  Previous studies have shown that polybrominated diphenyl ethers (PBDEs) behave as weak estrogens in animal and cell culture bioassays. In vivo metabolites of PBDEs are suspected to cause these effects.
  
  
  OBJECTIVE
  To identify candidate metabolites, mouse plasma samples were collected after continuous oral and subcutaneous exposure to DE-71, a widely used commercial pentabromodiphenyl ether product, for 34 days.
  
  
  METHODS
  Samples were extracted, separated into neutral and phenolic fractions, and analyzed by gas chromatographic mass spectrometry.
  
  
  RESULTS
  In the plasma samples of orally treated animals, 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE-153) represented 52% of total measurable PBDEs, whereas it represented only 4.3% in the DE-71 mixture. This suggested that BDE-153 was more persistent than other congeners in mice. Several metabolites were detected and quantitated: 2,4-dibromophenol, 2,4,5-tribromophenol, and six hydroxylated PBDEs. The presence of the two phenols suggested cleavage of the ether bond of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and 2,2',4,4',5-pentabromodiphenyl ether (BDE-99), respectively. The hydroxylated (HO)-PBDEs might come from hydroxylation or debromination/hydroxylation. Among the quantitated hydroxylated metabolites, the most abundant was 4-HO-2,2',3,4'-tetra-BDE, which suggested that there was a bromine shift during the hydroxylation process. para-HO-PBDEs have been proposed to behave as endocrine disruptors.
  
  
  CONCLUSIONS
  THERE SEEM TO BE THREE METABOLIC PATHWAYS: cleavage of the diphenyl ether bond, hydroxylation, and debromination/hydroxylation. The cleavage of the diphenyl ether bond formed bromophenols, and the other two pathways formed hydroxylated PBDEs, of which para-HO-PBDEs are most likely formed from BDE-47. These metabolites may be the most thyroxine-like and/or estrogen-like congeners among the HO-PBDEs.
authors.affiliation: School of Public and Environmental Affairs, Indiana University, Bloomington, Indiana 47405, USA.
authors.forename: Xinghua
authors.initials: X
authors.lastname: Qiu
authors.forename: Minerva
authors.initials: M
authors.lastname: Mercado-Feliciano
authors.forename: Robert M
authors.initials: RM
authors.lastname: Bigsby
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Hites
mesh_terms: D000818:Animals; D008401:Gas Chromatography-Mass Spectrometry; D006900:Hydroxylation; D051379:Mice; D011075:Polybrominated Biphenyls / Q000097:blood*
chemical_list: D011075:Polybrominated Biphenyls; C517828:hexabrominated diphenyl ether 153