Superfund Research Program
The Flame Retardant Firemaster 550, Fat Cells, and Bone Health
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Researchers from the Boston University (BU) and Duke University Superfund Research Program (SRP) Centers found that components of the flame-retardant mixture Firemaster® 550 (FM550) may stimulate growth of fat cells and reduce bone health. The results of the collaborative study suggest that triphenyl phosphate (TPP), a component of FM550 that is widespread in household products and house dust, interacts with a protein that regulates fat cell differentiation and lipid storage.
“TPP is everywhere in our indoor environment, so our finding that TPP is biologically active is significant and warrants further investigation,” said BU SRP project leader Jennifer Schlezinger, Ph.D., who led the study. “This calls attention to the fact that we need to be considering the contributions of environmental toxicants such as TPP in obesity and loss of bone health.”
Alternative flame retardant use has increased since the phase out of pentabromodiphenyl ethers (PBDEs) because of concerns about the tendency of PBDEs to concentrate in human tissues and potential human health effects such as neurodevelopmental delays. Other chemicals are currently used to meet flammability requirements, including FM550, which is found in foam-based products such as couch cushions and other household items. FM550 was recently identified as a common contaminant in household dust,1 but little information is available on how people are exposed to these new flame retardants or their potential health effects.
Working Collaboratively to Understand the Problem
“We pursued this work because of results from a small-scale study in pregnant rats led by Heather Stapleton, Ph.D., at Duke SRP. She found that perinatal exposure to FM550 in rats was associated with weight gain at low exposure levels,”2 said Schlezinger. “By collaborating with the Duke SRP Center, we were able to pool our resources from the biology and chemistry side of things to look at biological effects on cells and to see how the chemicals bind to regulators in the body.”
Because peroxisome proliferator activated receptor gamma (PPARγ) is known to regulate the development of fat cells in the body, scientists tested the ability of FM550 to bind and activate this protein. Researchers also used multipotent cells from bone marrow, which can form fat cells or bone cells, to assess changes in response to exposure to TPP and other components of FM550.
The alternative flame retardant mixture FM550 was shown to bind and activate PPARγ. The BU Computational Modeling Core, an integral component of the BU SRP, was able to simulate how FM550 fits into the PPARγ binding site. This interaction with PPARγ is likely the reason why FM550 was also shown to stimulate development of fat cells, which may contribute to obesity.
PPARγ also plays a crucial role in stimulating formation of fat cells in bone marrow, which suppresses the formation of osteoblasts, or bone cells. By activating PPARγ, components of FM550, including TPP, potentially have detrimental effects on bone health and may accelerate osteoporosis by suppressing osteoblast formation. Based on the findings, the researchers concluded that TPP is likely a major contributor to the biological actions of FM550.
From House Dust to Hands: Public Health Concerns
By collaborating with Tom Webster, Ph.D., a BU SRP project leader, the scientists were able to estimate children’s exposure to TPP from house dust using an indoor exposure model. Models in the study suggest that exposure to house dust is a major source of exposure for young children at home, with inhalation and skin absorption of TPP also playing a role. Previous findings by co-author Stapleton also suggest that toddlers have a significant amount of exposure to flame retardant chemicals because they transfer house dust particles from their hands to their mouths.3 According to the authors, this study validates the association between TPP and health effects and given that TPP is very common in house dust, continued investigation in warranted.
This work was supported by SRP grants P42ES007381 and P42ES010356, R01ES015829 and R01ES016099 from the National Institute of Environmental Health Sciences, and R01GM064700 from the National Institute of General Medical Sciences.
1Stapleton HM, Allen JG, Kelly SM, Konstantinov A, Klosterhaus S, Watkins D, McClean MD, Webster TF. 2008. Alternate and new brominated flame retardants detected in U.S. house dust. Environ Sci Technol 42(18):6910–6916. doi: 10.1021/es801070p
2Patisaul HB, Roberts SC, Mabrey N, McCaffrey KA, Gear RB, Braun J, Belcher SM, Stapleton HM. 2013. Accumulation and endocrine disrupting effects of the flame retardant mixture Firemaster® 550 in rats: an exploratory assessment. J Biochem Mol Toxicol 27(2): 124-136. doi: 10.1002/jbt.21439
3Stapleton HM, Eagle S, Sjödin A, Webster TF. 2012. Serum PBDEs in a North Carolina toddler cohort: associations with handwipes, house dust and socioeconomic variables. Environ Health Perspect 120(7):1049-1054. doi:10.1289/ehp.1104802
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To learn more about this research, please refer to the following sources:
- Pillai HK, Fang M, Beglov D, Kozakov D, Vajda S, Stapleton HM, Webster TF, Schlezinger JJ. 2014. Ligand binding and activation of PPARγ by Firemaster® 550: effects on adipogenesis and osteogenesis in vitro. Environ Health Perspect 122(11):1225-1232. doi:10.1289/ehp.1408111 PMID:25062436 PMCID:PMC4216168
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