title: Human liver microsome-mediated metabolism of brominated diphenyl ethers 47, 99, and 153 and identification of their major metabolites.
abstract: While the metabolism and excretion of polybrominated diphenyl ethers (PBDEs) have been reported in rodents, PBDE metabolism in humans has only recently been investigated. In this present study, individual human liver microsomes were incubated for 120 min with radiolabeled and nonradiolabeled BDE 47, 99, or 153 to determine their relative degrees of metabolism and to identify the structures of metabolites formed. Radiolabeled samples were analyzed using high-performance liquid chromatography/radiochemical detection, while nonradiolabeled samples were analyzed with and without derivatization using gas chromatography/mass spectrometry. Results from radiolabeled incubations demonstrated that human liver microsomes metabolized BDEs 47 and 99 but not BDE 153. Differences in the extent of BDE metabolism by the three individual liver specimens used in the study were observed. BDE 47 metabolized to a dihydroxylated BDE 47 and 2,4-dibromophenol, while BDE 99 metabolized to a dihydroxylated BDE 99, 2,4,5-tribromophenol and 1,3-dibromobenzene. This study showed that BDEs 47 and 99 are metabolized by human liver microsomes with relatively large interindividual differences. Results of this study could provide one explanation for the high bioaccumulation rate of BDE 153 in humans.
authors.affiliation: Department of Chemistry, University at Buffalo, State University of New York, Buffalo, New York 14260, USA.
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Lupton
authors.forename: Barbara P
authors.initials: BP
authors.lastname: McGarrigle
authors.forename: James R
authors.initials: JR
authors.lastname: Olson
authors.forename: Troy D
authors.initials: TD
authors.lastname: Wood
authors.forename: Diana S
authors.initials: DS
authors.lastname: Aga
mesh_terms: D002851:Chromatography, High Pressure Liquid; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D055768:Halogenated Diphenyl Ethers / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D008875:Middle Aged; D011075:Polybrominated Biphenyls / Q000737:chemistry / Q000378:metabolism*; D055815:Young Adult
chemical_list: C477694:2,2',4,4',5-brominated diphenyl ether; D055768:Halogenated Diphenyl Ethers; D011075:Polybrominated Biphenyls; C511295:2,2',4,4'-tetrabromodiphenyl ether; C478854:2,2',4,4',5,5'-hexabrominated diphenyl ether