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Characterizing the peroxisome proliferator-activated receptor (PPAR?) ligand binding potential of several major flame retardants, their metabolites, and chemical mixtures in house dust.

ABSTRACT: Accumulating evidence has shown that some environmental contaminants can alter adipogenesis and act as obesogens. Many of these contaminants act via the activation of the peroxisome proliferator-activated receptor ? (PPAR?) nuclear receptor.Our goal was to determine the PPAR? ligand binding potency of several major flame retardants, including polybrominated diphenyl ethers (PBDEs), halogenated phenols and bisphenols, and their metabolites. Ligand binding activity of indoor dust and its bioactivated extracts were also investigated.We used a commercially available fluorescence polarization ligand binding assay to investigate the binding potency of flame retardants and dust extracts to human PPAR? ligand-binding domain. Rosiglitazone was used as a positive control.Most of the tested compounds exhibited dose-dependent binding to PPAR?. Mono(2-ethylhexyl) tetrabromophthalate, halogenated bisphenols and phenols, and hydroxylated PBDEs were found to be potent PPAR? ligands. The most potent compound was 3-OH-BDE-47, with an IC50 (concentration required to reduce effect by 50%) of 0.24 ?M. The extent of halogenation and the position of the hydroxyl group strongly affected binding. In the dust samples, 21 of the 24 samples tested showed significant binding potency at a concentration of 3 mg dust equivalent (DEQ)/mL. A 3-16% increase in PPAR? binding potency was observed following bioactivation of the dust using rat hepatic S9 fractions.Our results suggest that several flame retardants are potential PPAR? ligands and that metabolism may lead to increased binding affinity. The PPAR? binding activity of house dust extracts at levels comparable to human exposure warrants further studies into agonistic or antagonistic activities and their potential health effects.

SUBMITTER: Fang M

PROVIDER: S-EPMC4314249 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Characterizing the peroxisome proliferator-activated receptor (PPARγ) ligand binding potential of several major flame retardants, their metabolites, and chemical mixtures in house dust.

Fang Mingliang M Webster Thomas F TF Ferguson P Lee PL Stapleton Heather M HM

Environmental health perspectives 20141014 2

<h4>Background</h4>Accumulating evidence has shown that some environmental contaminants can alter adipogenesis and act as obesogens. Many of these contaminants act via the activation of the peroxisome proliferator-activated receptor γ (PPARγ) nuclear receptor.<h4>Objectives</h4>Our goal was to determine the PPARγ ligand binding potency of several major flame retardants, including polybrominated diphenyl ethers (PBDEs), halogenated phenols and bisphenols, and their metabolites. Ligand binding act ...[more]

PMID: 25314719

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Project description:Restrictions on the use of polybrominated diphenyl ethers (PBDEs) have resulted in the increased use of alternate flame retardant chemicals to meet flammability standards. However, it has been difficult to determine which chemical formulations are currently being used in high volumes to meet flammability standards since the use of flame retardant formulations in consumer products is not transparent (i.e., not provided to customers). To investigate chemicals being used as replacements for PentaBDE in polyurethane foam, we analyzed foam samples from 26 different pieces of furniture purchased in the United States primarily between 2003 and 2009. Samples included foam from couches, chairs, mattress pads, pillows, and, in one case, foam from a sound-proofing system of a laboratory-grade dust sieve, and were analyzed using gas chromatography mass spectrometry. Fifteen of the foam samples contained the flame retardanttris(1,3-dichloro-2-propyl) phosphate (TDCPP; 1-5% by weight), four samples contained tris(1-chloro-2-propyl) phosphate (TCPP; 0.5 -22% by weight), one sample contained brominated chemicals found in a new flame retardant mixture called Firemaster 550 (4.2% by weight), and one foam sample collected from a futon likely purchased prior to 2004 contained PentaBDE (0.5% by weight). Due to the high frequency of detection of the chlorinated phosphate compounds in furniture foam,we analyzed extracts from 50 house dust samples collected between 2002 and 2007 in the Boston, MA area for TDCPP, TCPP, and another high volume use organophosphate-based flame retardant used in foam, triphenylphosphate (TPP). Detection frequencies for TDCPP and TPP in the dust samples were > 96% and were log normally distributed, similar to observations for PBDEs. TCPP was positively detected in dust in only 24% of the samples, but detection was significantly limited by a coelution problem. The geometric mean concentrations for TCPP, TDCPP, and TPP in house dust were 570, 1890, and 7360 ng/g, respectively, and maximum values detected in dust were 5490, 56,080 and 1,798,000 ng/g, respectively. These data suggest that levels of these organophosphate flame retardants are comparable, or in some cases greater than, levels of PBDEs in house dust. The high prevalence of these chemicals in foam and the high concentrations measured in dust (as high as 1.8 mg/g) warrant further studies to evaluate potential health effects from dust exposure, particularly for children.

Dataset Information

Characterizing the peroxisome proliferator-activated receptor (PPAR?) ligand binding potential of several major flame retardants, their metabolites, and chemical mixtures in house dust.

Publications

Characterizing the peroxisome proliferator-activated receptor (PPARγ) ligand binding potential of several major flame retardants, their metabolites, and chemical mixtures in house dust.

Similar Datasets

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