Measurement of polybrominated diphenyl ethers and metabolites in mouse plasma after exposure to a commercial pentabromodiphenyl ether mixture

Xinghua Qiu, Minerva Mercado-Feliciano, Robert Bigsby, Ronald A. Hites

Research output: Contribution to journalArticle

147 Citations (Scopus)

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 there 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.

Original languageEnglish
Pages (from-to)1052-1058
Number of pages7
JournalEnvironmental Health Perspectives
Volume115
Issue number7
DOIs
StatePublished - Jul 2007

Fingerprint

Halogenated Diphenyl Ethers
PBDE
Metabolites
ether
metabolite
Hydroxylation
Plasmas
plasma
Ether
cleavage
Estrogens
Animals
pentabromodiphenyl ether
exposure
Endocrine Disruptors
Bromine
endocrine disruptor
Bioassay
animal
Phenols

Keywords

  • BDE-153
  • Bromophenols
  • DE-71
  • Hydroxylated PBDEs
  • Hydroxylation
  • Polybrominated diphenyl ethers

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Public Health, Environmental and Occupational Health

Cite this

Measurement of polybrominated diphenyl ethers and metabolites in mouse plasma after exposure to a commercial pentabromodiphenyl ether mixture. / Qiu, Xinghua; Mercado-Feliciano, Minerva; Bigsby, Robert; Hites, Ronald A.

In: Environmental Health Perspectives, Vol. 115, No. 7, 07.2007, p. 1052-1058.

Research output: Contribution to journalArticle

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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 there 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.",
keywords = "BDE-153, Bromophenols, DE-71, Hydroxylated PBDEs, Hydroxylation, Polybrominated diphenyl ethers",
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T1 - Measurement of polybrominated diphenyl ethers and metabolites in mouse plasma after exposure to a commercial pentabromodiphenyl ether mixture

AU - Qiu, Xinghua

AU - Mercado-Feliciano, Minerva

AU - Bigsby, Robert

AU - Hites, Ronald A.

PY - 2007/7

Y1 - 2007/7

N2 - 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 there 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.

AB - 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 there 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.

KW - BDE-153

KW - Bromophenols

KW - DE-71

KW - Hydroxylated PBDEs

KW - Hydroxylation

KW - Polybrominated diphenyl ethers

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