? ? Children's Exposure to Flame Retardants: Effects on Thyroid Hormone Regulation. The flame retardant chemicals polybrominated diphenyl ethers (PBDEs) are persistent and ubiquitous pollutants, particularly in indoor environments. Human biomonitoring studies have shown that levels of PBDEs are more than an order of magnitude higher in the United States population relative to any other region measured, including other industrialized countries in Europe. Furthermore, children between the ages of 0-4 are predicted to have the highest exposure and body burdens of PBDEs due to placental transfer, breast milk ingestion and inadvertent dust ingestion. Children's exposure is of concern because laboratory studies using animal models have found that PBDEs exert negative effects on thyroid hormone homeostasis, which is more pronounced in newborn animals relative to adults. The central hypothesis of this proposed study is that children in the United States are receiving greater exposure to PBDEs from inadvertent dust ingestion, leading to adverse effects on thyroid hormone regulation. The objectives of this study are threefold: 1) to measure children's (ages 1-4) exposure to PBDEs from indoor dust, determine ingestion rates from hand to mouth contact, and measure serum levels of PBDEs in these children; 2) to determine the products of hepatic metabolism of PBDEs; and 3) to determine the effects of PBDEs and their metabolites on intra- and extra-cellular thyroid hormone regulation to elucidate the mechanisms of action for thyroid toxicity. Using in vitro assays the following will be investigated: the effects of PBDEs and their metabolites on intracellular thyroid hormone levels, deiodinase (DI) enzyme activity, mRNA expression of thyroid regulating genes, and specific binding to thyroid binding globulin. The principal investigator also plans to develop and validate a new method to measure thyroid hormone levels and DI activity using liquid chromatography tandem mass spectrometry (LC/MS-MS), which will use stable isotopes instead of radio-labeled isotopes used in more traditional methods. This method could then be used as a screening tool for assessing effects of chemicals on intra-cellular thyroid regulation mediated by DI enzymes. Data gathered from this project will increase the understanding of PBDE effects on thyroid hormone regulation and aid in understanding children's developmental health risks from exposure to flame retardant chemicals in indoor environments. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
1R01ES016099-01A1
Application #
7540236
Study Section
Special Emphasis Panel (ZES1-JAB-C (R2))
Program Officer
Heindel, Jerrold
Project Start
2008-08-15
Project End
2013-06-30
Budget Start
2008-08-15
Budget End
2009-06-30
Support Year
1
Fiscal Year
2008
Total Cost
$529,872
Indirect Cost
Name
Duke University
Department
Type
Schools of Earth Sciences/Natur
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Phillips, Allison L; Hammel, Stephanie C; Hoffman, Kate et al. (2018) Children's residential exposure to organophosphate ester flame retardants and plasticizers: Investigating exposure pathways in the TESIE study. Environ Int 116:176-185
Kassotis, Christopher D; Kollitz, Erin M; Ferguson, Patrick Lee et al. (2018) Nonionic Ethoxylated Surfactants Induce Adipogenesis in 3T3-L1 Cells. Toxicol Sci 162:124-136
Hammel, Stephanie C; Phillips, Allison L; Hoffman, Kate et al. (2018) Evaluating the Use of Silicone Wristbands To Measure Personal Exposure to Brominated Flame Retardants. Environ Sci Technol :
Luz, Anthony L; Kassotis, Christopher D; Stapleton, Heather M et al. (2018) The high-production volume fungicide pyraclostrobin induces triglyceride accumulation associated with mitochondrial dysfunction, and promotes adipocyte differentiation independent of PPAR? activation, in 3T3-L1 cells. Toxicology 393:150-159
Rock, Kylie D; Horman, Brian; Phillips, Allison L et al. (2018) EDC IMPACT: Molecular effects of developmental FM 550 exposure in Wistar rat placenta and fetal forebrain. Endocr Connect 7:305-324
Kassotis, Christopher D; Nagel, Susan C; Stapleton, Heather M (2018) Unconventional oil and gas chemicals and wastewater-impacted water samples promote adipogenesis via PPAR?-dependent and independent mechanisms in 3T3-L1 cells. Sci Total Environ 640-641:1601-1610
Kassotis, Christopher D; Masse, Lauren; Kim, Stephanie et al. (2017) Characterization of Adipogenic Chemicals in Three Different Cell Culture Systems: Implications for Reproducibility Based on Cell Source and Handling. Sci Rep 7:42104
Phillips, Allison L; Hammel, Stephanie C; Konstantinov, Alex et al. (2017) Characterization of Individual Isopropylated and tert-Butylated Triarylphosphate (ITP and TBPP) Isomers in Several Commercial Flame Retardant Mixtures and House Dust Standard Reference Material SRM 2585. Environ Sci Technol 51:13443-13449
Baldwin, Kylie R; Phillips, Allison L; Horman, Brian et al. (2017) Sex Specific Placental Accumulation and Behavioral Effects of Developmental Firemaster 550 Exposure in Wistar Rats. Sci Rep 7:7118
Hoffman, Kate; Webster, Thomas F; Sjödin, Andreas et al. (2017) Toddler's behavior and its impacts on exposure to polybrominated diphenyl ethers. J Expo Sci Environ Epidemiol 27:193-197

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