| Measurement of Polybrominated Diphenyl Ethers and Metabolites in Mouse Plasma after Exposure to a Commercial Pentabromodiphenyl Ether Mixture Xinghua Qiu,1 Minerva Mercado-Feliciano,2 Robert M. Bigsby,3 and Ronald A. Hites1 1School of Public and Environmental Affairs, Indiana University, Bloomington, Indiana, USA; 2Department of Pharmacology and Toxicology, School of Medicine, Indiana University, Bloomington, Indiana, USA; 3Department of Obstetrics and Gynecology, School of Medicine, Indiana University, Indianapolis, Indiana, USA 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. Objectives: 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. Key words: BDE-153, bromophenols, DE-71, hydroxylated PBDEs, hydroxylation, polybrominated diphenyl ethers. Environ Health Perspect 115:1052–1058 (2007) . doi:10.1289/ehp.10011 available via http://dx.doi.org/ [Online 6 April 2007]
Address correspondence to R.A. Hites, School of Public and Environmental Affairs, Indiana University, 1315 E. 10th St., Bloomington, IN 47405 USA. Telephone: (812) 855-0193. Fax: (812) 855-1076. E-mail: HitesR@indiana.edu We thank G. Marsh, who provided most of the HO-PBDE standards used in this research. This study was supported by grant ES013341 from the National Institute of Environmental Health Sciences (M.M.F.) . The authors declare they have no competing financial interests. Received 18 December 2006 ; accepted 6 April 2007.
Correction In Figure 3 of the original manuscript published online, the arrows indicating pathways were incorrect. They have been corrected here.
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