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Aryl phosphate esters within a major PentaBDE replacement product induce cardiotoxicity in developing zebrafish embryos: potential role of the aryl hydrocarbon receptor.

Publication ,  Journal Article
McGee, SP; Konstantinov, A; Stapleton, HM; Volz, DC
Published in: Toxicological sciences : an official journal of the Society of Toxicology
May 2013

Firemaster 550 (FM550) is an additive flame retardant formulation of brominated and aryl phosphate ester (APE) components introduced as a major replacement product for the commercial polybrominated diphenyl ether mixture (known as PentaBDE) used primarily in polyurethane foam. However, little is known about the potential effects of FM550-based ingredients during early vertebrate development. Therefore, we first screened the developmental toxicity of each FM550 component using zebrafish as an animal model. Based on these initial screening assays, we found that exposure to the brominated components as high as 10µM resulted in no significant effects on embryonic survival or development, whereas exposure to triphenyl phosphate (TPP) or mono-substituted isopropylated triaryl phosphate (mono-ITP)-two APEs comprising almost 50% of FM550-resulted in targeted effects on cardiac looping and function during embryogenesis. As these cardiac abnormalities resembled aryl hydrocarbon receptor (AHR) agonist-induced phenotypes, we then exposed developing embryos to TPP or mono-ITP in the presence or absence of an AHR antagonist (CH223191) or AHR2-specific morpholino. Based on these studies, we found that CH223191 blocked heart malformations following exposure to mono-ITP but not TPP, whereas AHR2 knockdown failed to block the cardiotoxic effects of both components. Finally, using a cell-based human AHR reporter assay, we found that mono-ITP (but not TPP) exposure resulted in a significant increase in human AHR-driven luciferase activity at similar nominal concentrations as a potent reference AHR agonist (β-naphthoflavone). Overall, our findings suggest that two major APE components of FM550 induce severe cardiac abnormalities during early vertebrate development.

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Published In

Toxicological sciences : an official journal of the Society of Toxicology

DOI

EISSN

1096-0929

ISSN

1096-6080

Publication Date

May 2013

Volume

133

Issue

1

Start / End Page

144 / 156

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • Toxicology
  • Receptors, Aryl Hydrocarbon
  • Real-Time Polymerase Chain Reaction
  • Organophosphates
  • Molecular Structure
  • Humans
  • Heart Defects, Congenital
  • Heart
 

Citation

APA
Chicago
ICMJE
MLA
NLM
McGee, S. P., Konstantinov, A., Stapleton, H. M., & Volz, D. C. (2013). Aryl phosphate esters within a major PentaBDE replacement product induce cardiotoxicity in developing zebrafish embryos: potential role of the aryl hydrocarbon receptor. Toxicological Sciences : An Official Journal of the Society of Toxicology, 133(1), 144–156. https://doi.org/10.1093/toxsci/kft020
McGee, Sean P., Alex Konstantinov, Heather M. Stapleton, and David C. Volz. “Aryl phosphate esters within a major PentaBDE replacement product induce cardiotoxicity in developing zebrafish embryos: potential role of the aryl hydrocarbon receptor.Toxicological Sciences : An Official Journal of the Society of Toxicology 133, no. 1 (May 2013): 144–56. https://doi.org/10.1093/toxsci/kft020.
McGee SP, Konstantinov A, Stapleton HM, Volz DC. Aryl phosphate esters within a major PentaBDE replacement product induce cardiotoxicity in developing zebrafish embryos: potential role of the aryl hydrocarbon receptor. Toxicological sciences : an official journal of the Society of Toxicology. 2013 May;133(1):144–56.
McGee, Sean P., et al. “Aryl phosphate esters within a major PentaBDE replacement product induce cardiotoxicity in developing zebrafish embryos: potential role of the aryl hydrocarbon receptor.Toxicological Sciences : An Official Journal of the Society of Toxicology, vol. 133, no. 1, May 2013, pp. 144–56. Epmc, doi:10.1093/toxsci/kft020.
McGee SP, Konstantinov A, Stapleton HM, Volz DC. Aryl phosphate esters within a major PentaBDE replacement product induce cardiotoxicity in developing zebrafish embryos: potential role of the aryl hydrocarbon receptor. Toxicological sciences : an official journal of the Society of Toxicology. 2013 May;133(1):144–156.
Journal cover image

Published In

Toxicological sciences : an official journal of the Society of Toxicology

DOI

EISSN

1096-0929

ISSN

1096-6080

Publication Date

May 2013

Volume

133

Issue

1

Start / End Page

144 / 156

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • Toxicology
  • Receptors, Aryl Hydrocarbon
  • Real-Time Polymerase Chain Reaction
  • Organophosphates
  • Molecular Structure
  • Humans
  • Heart Defects, Congenital
  • Heart