Measurement of Polybrominated Diphenyl Ethers and Metabolites in Mouse Plasma after Exposure to a Commercial Pentabromodiphenyl Ether Mixture

Abstract

BackgroundPrevious 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.ObjectivesTo 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.MethodsSamples were extracted, separated into neutral and phenolic fractions, and analyzed by gas chromatographic mass spectrometry.ResultsIn 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.ConclusionsThere 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.

Hydroxylated PBDEs and brominated phenolic compounds in particulate matters emitted during recycling of waste printed circuit boards in a typical e-waste workshop of South China

“…The most abundant BP congener was 2,4,6-triBP, accounting for 65.0% of the total BPs concentration, followed by 2,4-diBP (32.1%) and 2,6-diBP (2.81%). This BPs profile was quite different from that in mouse plasma exposed to commercial PBDE mixture, in which 2,4,5-triBP was the most abundant congener, accounting for 49.8e 56.3% of the three detected BP congeners (2,4-diBP, 2,4,5-triBP and 2,4,6-triBP), whereas 2,4,6-triBP was only accounted for 3.43e 3.76% (Qiu et al, 2007). This difference might be due to the different formation pathways of BPs in mouse plasma from this study.…”

“…It was reported that OH-PBDE metabolites from laboratory studies in animals were dominated by hydroxyl groups in the meta or para positions (Malmberg et al, 2005;Marsh et al, 2006;Qiu et al, 2007). Ortho OH-substituted OH-PBDEs have been identified as naturally occurring formulations in marine organisms such as sponges, tunicates, and algae (Fu et al, 1995;Malmvarn et al, 2005;Unson et al, 1994).…”

“…Hydroxylated PBDEs (OH-PBDEs), which are a relatively new group of phenolic compounds, have been detected in biological samples including fish (Marsh et al, 2004;Valters et al, 2005), algae (Malmvarn et al, 2005(Malmvarn et al, , 2008, birds (Verreault et al, 2005), rats and mice (Malmberg et al, 2005;Qiu et al, 2007), as well as human blood Qiu et al, 2009;Yu et al, 2010). It has been shown that OH-PBDEs can be naturally formed in marine algae or by their associated microorganisms (Malmvarn et al, 2005(Malmvarn et al, , 2008Unson et al, 1994).…”

“…Additionally, BPs can also be formed by several marine organisms and have been identified as a key natural flavor component of marine fish (Hassenklover et al, 2006;Whitfield et al, 1998). Some BPs (2,4-diBP, 2,4,5-triBP and 2,4,6-triBP) were the metabolites of PBDEs in mice (Qiu et al, 2007). BPs may play a role in chemical defense and deterrence to ecology (Woodin et al, 1997).…”

Levels and distribution of methoxylated and hydroxylated polybrominated diphenyl ethers in plant and soil samples surrounding a seafood processing factory and a seafood market

“…These orthosubstituted OH-PBDEs and MeO-PBDEs have been structurally identified and confirmed as natural compounds (Malmvarn et al, 2005(Malmvarn et al, , 2008. The meta-and para-substituted OH-PBDEs have been reported to be biotransformation products produced during PBDE exposure (Malmberg et al, 2005;Marsh et al, 2006;Qiu et al, 2007). Recently, Wan et al demonstrated the interconversion of OH-PBDE and MeO-PBDE in Japanese medaka (Wan et al, 2010).…”