Analysis of Ah receptor pathway activation by brominated flame retardants

David J. Brown, Ilse Van Overmeire, Leo Goeyens, Michael S. Denison, Michael J. De Vito, George C. Clark

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Brominated flame-retardants (BFRs) are used as additives in plastics to decrease the rate of combustion of these materials, leading to greater consumer safety. As the use of plastics has increased, the production and use of flame-retardants has also grown. Many BFRs are persistent and have been detected in environmental samples, raising concerns about the biological/toxicological risk associated with their use. Most BFRs appear to be non-toxic, however there is still some concern that these compounds, or possible contaminants in BFRs mixtures could interact with cellular receptors. In this study we have examined the interaction of decabromodiphenyl ether, Firemaster BP4A (tetrabromobisphenol A), Firemaster PHT4 (tetrabromophthalic anhydride), hexabromobenzene, pentabromotoluene, decabromobiphenyl, Firemaster BP-6 (2,2,4, 4,5,5-hexabromobiphenyl) and possible contaminants of BFR mixtures with the Ah receptor. Receptor binding and activation was examined using the Gel Retardation Assay and increased expression of dioxin responsive genes was detected using the reporter gene based CALUX assay. The results demonstrate the ability of BFRs to activate the AhR signal transduction pathway at moderate to high concentrations as assessed using both assays. AhR-dependent activation by BFRs may be due in part to contaminants present in commercial/technical mixtures. This was suggested by our comparative analysis of Firemaster BP-6 versus its primary component 2,2, 4,4,5,5-hexabromobiphenyl. Some technical mixtures of brominated flame-retardants contain brominated biphenyls, dioxins or dibenzofurans as contaminants. When tested in the CALUX assay these compounds were found to be equivalent to, or more active than their chlorinated analogues. Relative effective potency values were determined from dose response curves for these brominated HAHs.

Original languageEnglish (US)
Pages (from-to)1509-1518
Number of pages10
JournalChemosphere
Volume55
Issue number11
DOIs
StatePublished - Jun 2004

Fingerprint

Flame Retardants
Flame retardants
Chemical activation
Assays
assay
Impurities
Dioxins
pollutant
decabromobiphenyl ether
dioxin
Plastics
Genes
plastic
flame retardant
analysis
Signal transduction
gene
dibenzofuran
Electrophoretic Mobility Shift Assay
Reporter Genes

Keywords

  • AhR, aryl hydrocarbon receptor
  • BFRs, brominated flame-retardants
  • CALUX, chemically activated luciferase expression assay
  • CYPA1A1, cytochrome P4501A1 gene
  • DMSO, dimethyl sulfoxide
  • DRE, dioxin responsive element

ASJC Scopus subject areas

  • Environmental Chemistry
  • Environmental Science(all)

Cite this

Brown, D. J., Van Overmeire, I., Goeyens, L., Denison, M. S., De Vito, M. J., & Clark, G. C. (2004). Analysis of Ah receptor pathway activation by brominated flame retardants. Chemosphere, 55(11), 1509-1518. https://doi.org/10.1016/j.chemosphere.2003.10.019

Analysis of Ah receptor pathway activation by brominated flame retardants. / Brown, David J.; Van Overmeire, Ilse; Goeyens, Leo; Denison, Michael S.; De Vito, Michael J.; Clark, George C.

In: Chemosphere, Vol. 55, No. 11, 06.2004, p. 1509-1518.

Research output: Contribution to journalArticle

Brown, DJ, Van Overmeire, I, Goeyens, L, Denison, MS, De Vito, MJ & Clark, GC 2004, 'Analysis of Ah receptor pathway activation by brominated flame retardants', Chemosphere, vol. 55, no. 11, pp. 1509-1518. https://doi.org/10.1016/j.chemosphere.2003.10.019
Brown DJ, Van Overmeire I, Goeyens L, Denison MS, De Vito MJ, Clark GC. Analysis of Ah receptor pathway activation by brominated flame retardants. Chemosphere. 2004 Jun;55(11):1509-1518. https://doi.org/10.1016/j.chemosphere.2003.10.019
Brown, David J. ; Van Overmeire, Ilse ; Goeyens, Leo ; Denison, Michael S. ; De Vito, Michael J. ; Clark, George C. / Analysis of Ah receptor pathway activation by brominated flame retardants. In: Chemosphere. 2004 ; Vol. 55, No. 11. pp. 1509-1518.
@article{58599b2138f04b7e91f0376bc27326a3,
title = "Analysis of Ah receptor pathway activation by brominated flame retardants",
abstract = "Brominated flame-retardants (BFRs) are used as additives in plastics to decrease the rate of combustion of these materials, leading to greater consumer safety. As the use of plastics has increased, the production and use of flame-retardants has also grown. Many BFRs are persistent and have been detected in environmental samples, raising concerns about the biological/toxicological risk associated with their use. Most BFRs appear to be non-toxic, however there is still some concern that these compounds, or possible contaminants in BFRs mixtures could interact with cellular receptors. In this study we have examined the interaction of decabromodiphenyl ether, Firemaster BP4A (tetrabromobisphenol A), Firemaster PHT4 (tetrabromophthalic anhydride), hexabromobenzene, pentabromotoluene, decabromobiphenyl, Firemaster BP-6 (2,2′,4, 4′,5,5′-hexabromobiphenyl) and possible contaminants of BFR mixtures with the Ah receptor. Receptor binding and activation was examined using the Gel Retardation Assay and increased expression of dioxin responsive genes was detected using the reporter gene based CALUX assay. The results demonstrate the ability of BFRs to activate the AhR signal transduction pathway at moderate to high concentrations as assessed using both assays. AhR-dependent activation by BFRs may be due in part to contaminants present in commercial/technical mixtures. This was suggested by our comparative analysis of Firemaster BP-6 versus its primary component 2,2′, 4,4′,5,5′-hexabromobiphenyl. Some technical mixtures of brominated flame-retardants contain brominated biphenyls, dioxins or dibenzofurans as contaminants. When tested in the CALUX assay these compounds were found to be equivalent to, or more active than their chlorinated analogues. Relative effective potency values were determined from dose response curves for these brominated HAHs.",
keywords = "AhR, aryl hydrocarbon receptor, BFRs, brominated flame-retardants, CALUX, chemically activated luciferase expression assay, CYPA1A1, cytochrome P4501A1 gene, DMSO, dimethyl sulfoxide, DRE, dioxin responsive element",
author = "Brown, {David J.} and {Van Overmeire}, Ilse and Leo Goeyens and Denison, {Michael S.} and {De Vito}, {Michael J.} and Clark, {George C.}",
year = "2004",
month = "6",
doi = "10.1016/j.chemosphere.2003.10.019",
language = "English (US)",
volume = "55",
pages = "1509--1518",
journal = "Chemosphere",
issn = "0045-6535",
publisher = "Elsevier Limited",
number = "11",

}

TY - JOUR

T1 - Analysis of Ah receptor pathway activation by brominated flame retardants

AU - Brown, David J.

AU - Van Overmeire, Ilse

AU - Goeyens, Leo

AU - Denison, Michael S.

AU - De Vito, Michael J.

AU - Clark, George C.

PY - 2004/6

Y1 - 2004/6

N2 - Brominated flame-retardants (BFRs) are used as additives in plastics to decrease the rate of combustion of these materials, leading to greater consumer safety. As the use of plastics has increased, the production and use of flame-retardants has also grown. Many BFRs are persistent and have been detected in environmental samples, raising concerns about the biological/toxicological risk associated with their use. Most BFRs appear to be non-toxic, however there is still some concern that these compounds, or possible contaminants in BFRs mixtures could interact with cellular receptors. In this study we have examined the interaction of decabromodiphenyl ether, Firemaster BP4A (tetrabromobisphenol A), Firemaster PHT4 (tetrabromophthalic anhydride), hexabromobenzene, pentabromotoluene, decabromobiphenyl, Firemaster BP-6 (2,2′,4, 4′,5,5′-hexabromobiphenyl) and possible contaminants of BFR mixtures with the Ah receptor. Receptor binding and activation was examined using the Gel Retardation Assay and increased expression of dioxin responsive genes was detected using the reporter gene based CALUX assay. The results demonstrate the ability of BFRs to activate the AhR signal transduction pathway at moderate to high concentrations as assessed using both assays. AhR-dependent activation by BFRs may be due in part to contaminants present in commercial/technical mixtures. This was suggested by our comparative analysis of Firemaster BP-6 versus its primary component 2,2′, 4,4′,5,5′-hexabromobiphenyl. Some technical mixtures of brominated flame-retardants contain brominated biphenyls, dioxins or dibenzofurans as contaminants. When tested in the CALUX assay these compounds were found to be equivalent to, or more active than their chlorinated analogues. Relative effective potency values were determined from dose response curves for these brominated HAHs.

AB - Brominated flame-retardants (BFRs) are used as additives in plastics to decrease the rate of combustion of these materials, leading to greater consumer safety. As the use of plastics has increased, the production and use of flame-retardants has also grown. Many BFRs are persistent and have been detected in environmental samples, raising concerns about the biological/toxicological risk associated with their use. Most BFRs appear to be non-toxic, however there is still some concern that these compounds, or possible contaminants in BFRs mixtures could interact with cellular receptors. In this study we have examined the interaction of decabromodiphenyl ether, Firemaster BP4A (tetrabromobisphenol A), Firemaster PHT4 (tetrabromophthalic anhydride), hexabromobenzene, pentabromotoluene, decabromobiphenyl, Firemaster BP-6 (2,2′,4, 4′,5,5′-hexabromobiphenyl) and possible contaminants of BFR mixtures with the Ah receptor. Receptor binding and activation was examined using the Gel Retardation Assay and increased expression of dioxin responsive genes was detected using the reporter gene based CALUX assay. The results demonstrate the ability of BFRs to activate the AhR signal transduction pathway at moderate to high concentrations as assessed using both assays. AhR-dependent activation by BFRs may be due in part to contaminants present in commercial/technical mixtures. This was suggested by our comparative analysis of Firemaster BP-6 versus its primary component 2,2′, 4,4′,5,5′-hexabromobiphenyl. Some technical mixtures of brominated flame-retardants contain brominated biphenyls, dioxins or dibenzofurans as contaminants. When tested in the CALUX assay these compounds were found to be equivalent to, or more active than their chlorinated analogues. Relative effective potency values were determined from dose response curves for these brominated HAHs.

KW - AhR, aryl hydrocarbon receptor

KW - BFRs, brominated flame-retardants

KW - CALUX, chemically activated luciferase expression assay

KW - CYPA1A1, cytochrome P4501A1 gene

KW - DMSO, dimethyl sulfoxide

KW - DRE, dioxin responsive element

UR - http://www.scopus.com/inward/record.url?scp=1942425674&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1942425674&partnerID=8YFLogxK

U2 - 10.1016/j.chemosphere.2003.10.019

DO - 10.1016/j.chemosphere.2003.10.019

M3 - Article

C2 - 15099731

AN - SCOPUS:1942425674

VL - 55

SP - 1509

EP - 1518

JO - Chemosphere

JF - Chemosphere

SN - 0045-6535

IS - 11

ER -