Journal
TOXICOLOGY LETTERS
Volume 228, Issue 2, Pages 93-102Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2014.04.017
Keywords
Apoptosis Endocrine disruptor; Flame retardant; Nuclear receptors; Obesity; Peroxisome proliferator-activated receptor
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Funding
- University of Cincinnati Center for Environmental Genetics [NIEHS P30-ES006096]
- NCSU Center for Human Health and the Environment (CHHE) awarded
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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 PPAR-y. As a result, the concentration response relationships and relative activities of FM 550 at PPAR-y were investigated in more detail with the contribution of each chemical component defined and compared to the activities of the prototypical PPAR-y 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-y, and have identified TPP as a candidate metabolic disruptor that also acts as a cytotoxicant. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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