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.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
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Special Emphasis Panel (ZES1-JAB-C (R2))
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Heindel, Jerrold
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Duke University
Schools of Earth Sciences/Natur
United States
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Hoffman, Kate; Fang, Mingliang; Horman, Brian et al. (2014) Urinary tetrabromobenzoic acid (TBBA) as a biomarker of exposure to the flame retardant mixture Firemaster® 550. Environ Health Perspect 122:963-9
Noyes, Pamela D; Lema, Sean C; Roberts, Simon C et al. (2014) Rapid method for the measurement of circulating thyroid hormones in low volumes of teleost fish plasma by LC-ESI/MS/MS. Anal Bioanal Chem 406:715-26
Dishaw, Laura V; Macaulay, Laura J; Roberts, Simon C et al. (2014) Exposures, mechanisms, and impacts of endocrine-active flame retardants. Curr Opin Pharmacol 19:125-33
Pillai, Hari K; Fang, Mingliang; Beglov, Dmitri et al. (2014) Ligand binding and activation of PPAR? by Firemaster® 550: effects on adipogenesis and osteogenesis in vitro. Environ Health Perspect 122:1225-32
Muzzio, Amanda M; Noyes, Pamela D; Stapleton, Heather M et al. (2014) Tissue distribution and thyroid hormone effects on mRNA abundance for membrane transporters Mct8, Mct10, and organic anion-transporting polypeptides (Oatps) in a teleost fish. Comp Biochem Physiol A Mol Integr Physiol 167:77-89
Stapleton, Heather M; Misenheimer, John; Hoffman, Kate et al. (2014) Flame retardant associations between children's handwipes and house dust. Chemosphere 116:54-60
Dong, Wu; Macaulay, Laura J; Kwok, Kevin W H et al. (2013) Using whole mount in situ hybridization to examine thyroid hormone deiodinase expression in embryonic and larval zebrafish: a tool for examining OH-BDE toxicity to early life stages. Aquat Toxicol 132-133:190-9
Carignan, Courtney C; McClean, Michael D; Cooper, Ellen M et al. (2013) Predictors of tris(1,3-dichloro-2-propyl) phosphate metabolite in the urine of office workers. Environ Int 55:56-61
Noyes, Pamela D; Lema, Sean C; Macaulay, Laura J et al. (2013) Low level exposure to the flame retardant BDE-209 reduces thyroid hormone levels and disrupts thyroid signaling in fathead minnows. Environ Sci Technol 47:10012-21
Meeker, John D; Cooper, Ellen M; Stapleton, Heather M et al. (2013) Urinary metabolites of organophosphate flame retardants: temporal variability and correlations with house dust concentrations. Environ Health Perspect 121:580-5

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