In vitro assessment of human nuclear hormone receptor activity and cytotoxicity of the flame retardant mixture FM 550 and its triarylphosphate and brominated components.
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.
Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0575, USA. Electronic address: scott.belcher@uc.edu.
Scott M
SM
Belcher
Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0575, USA.
Clifford J
CJ
Cookman
Department of Biological Sciences, Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, USA.
Heather B
HB
Patisaul
Nicholas School of the Environment, Duke University, Durham, NC, USA.
Heather M
HM
Stapleton
D017667:Adipocytes / Q000187:drug effects; D000818:Animals; D016466:CHO Cells; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects*; D006224:Cricetinae; D003412:Cricetulus; D052244:Endocrine Disruptors / Q000633:toxicity*; D005411:Flame Retardants / Q000633:toxicity*; D006801:Humans; D008024:Ligands; D010755:Organophosphates / Q000737:chemistry / Q000633:toxicity*; D009947:Organotin Compounds / Q000633:toxicity; D047495:PPAR gamma / Q000187:drug effects / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects*; D015533:Transcriptional Activation / Q000187:drug effects
D052244:Endocrine Disruptors; D005411:Flame Retardants; D008024:Ligands; D010755:Organophosphates; D009947:Organotin Compounds; D047495:PPAR gamma; D018160:Receptors, Cytoplasmic and Nuclear; D053148:Caspase 3
Apoptosis; Endocrine disruptor; Flame retardant; Nuclear receptors; Obesity; Peroxisome proliferator-activated receptor