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In vitro assessment of human nuclear hormone receptor activity and cytotoxicity of the flame retardant mixture FM 550 and its triarylphosphate and brominated components.

Publication ,  Journal Article
Belcher, SM; Cookman, CJ; Patisaul, HB; Stapleton, HM
Published in: Toxicology letters
July 2014

Firemaster(®) 550 (FM 550) is a mixture of brominated and triarylphosphate flame retardants used in polyurethane foam-based products. The primary components are also used in numerous other applications and are thus common household and industrial contaminants. Our previous animal studies suggested that FM 550 exposure may alter metabolism and cause weight gain. Employing human nuclear receptor (NR) luciferase reporter assays, the goal of this study was to evaluate the agonist actions of FM 550 and its constituent compounds at NRs with known roles in establishing or regulating energy balance. FM 550 was found to have significant agonist activity only at the master regulator of adipocyte differentiation PPARγ. As a result, the concentration response relationships and relative activities of FM 550 at PPARγ were investigated in more detail with the contribution of each chemical component defined and compared to the activities of the prototypical PPARγ environmental ligands triphenyltin and tributyltin. The resulting data indicated that the primary metabolic disruptive effects of FM 550 were likely mediated by the activity of the triarylphosphates at PPARγ, and have identified TPP as a candidate metabolic disruptor that also acts as a cytotoxicant.

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Published In

Toxicology letters

DOI

EISSN

1879-3169

ISSN

0378-4274

Publication Date

July 2014

Volume

228

Issue

2

Start / End Page

93 / 102

Related Subject Headings

  • Transcriptional Activation
  • Toxicology
  • Receptors, Cytoplasmic and Nuclear
  • PPAR gamma
  • Organotin Compounds
  • Organophosphates
  • Ligands
  • Humans
  • Flame Retardants
  • Endocrine Disruptors
 

Citation

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Belcher, S. M., Cookman, C. J., Patisaul, H. B., & Stapleton, H. M. (2014). In vitro assessment of human nuclear hormone receptor activity and cytotoxicity of the flame retardant mixture FM 550 and its triarylphosphate and brominated components. Toxicology Letters, 228(2), 93–102. https://doi.org/10.1016/j.toxlet.2014.04.017
Belcher, Scott M., Clifford J. Cookman, Heather B. Patisaul, and Heather M. Stapleton. “In vitro assessment of human nuclear hormone receptor activity and cytotoxicity of the flame retardant mixture FM 550 and its triarylphosphate and brominated components.Toxicology Letters 228, no. 2 (July 2014): 93–102. https://doi.org/10.1016/j.toxlet.2014.04.017.
Belcher, Scott M., et al. “In vitro assessment of human nuclear hormone receptor activity and cytotoxicity of the flame retardant mixture FM 550 and its triarylphosphate and brominated components.Toxicology Letters, vol. 228, no. 2, July 2014, pp. 93–102. Epmc, doi:10.1016/j.toxlet.2014.04.017.
Journal cover image

Published In

Toxicology letters

DOI

EISSN

1879-3169

ISSN

0378-4274

Publication Date

July 2014

Volume

228

Issue

2

Start / End Page

93 / 102

Related Subject Headings

  • Transcriptional Activation
  • Toxicology
  • Receptors, Cytoplasmic and Nuclear
  • PPAR gamma
  • Organotin Compounds
  • Organophosphates
  • Ligands
  • Humans
  • Flame Retardants
  • Endocrine Disruptors