ABSTRACT
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 FM550 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 PPAR. As a result, the concentration response relationships and relative activities of FM 550 at PPAR were investigated in more detail with the contribution of each chemical component defined and compared to the activities of the prototypical PPAR 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 PPAR, and have identified TPP as a candidate metabolic disruptor that also acts as a cytotoxicant.
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Date of publication: 28 April 2014; Science Direct: Elsevier, Toxicology Letters
Author information: Scott M. Belcher (1); Clifford J. Cookman (1); Heather B. Patisaul (2); & Heather M. Stapleton (3)
(1) Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0575, USA
(2) Department of Biological Sciences, Center for Human Heath and the Environment, North Carolina State University, Raleigh, NC, USA
(3) Nicholas School of the Environment, Duke University, Durham, NC, USA