Children's Exposure to Flame Retardants: Effects on Thyroid Hormone Regulation

Summary

Principal Investigator: HEATHER STAPLETON
Affiliation: Duke University Medical Center
Country: USA
Abstract: DESCRIPTION (provided by applicant) 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.
Funding Period: ----------------2008 - ---------------2013-
more information: NIH RePORT

Top Publications

  1. pmc Early zebrafish embryogenesis is susceptible to developmental TDCPP exposure
    Sean P McGee
    Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina 29208, USA
    Environ Health Perspect 120:1585-91. 2012
  2. pmc Accumulation and endocrine disrupting effects of the flame retardant mixture Firemaster® 550 in rats: an exploratory assessment
    Heather B Patisaul
    Department of Biology, North Carolina State University, Raleigh, NC 27695, USA
    J Biochem Mol Toxicol 27:124-36. 2013
  3. pmc Novel and high volume use flame retardants in US couches reflective of the 2005 PentaBDE phase out
    Heather M Stapleton
    Nicholas School of the Environment, Duke University, Durham, North Carolina, USA
    Environ Sci Technol 46:13432-9. 2012
  4. pmc Associations between brominated flame retardants in house dust and hormone levels in men
    Paula I Johnson
    Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109, USA
    Sci Total Environ 445:177-84. 2013
  5. pmc Urinary metabolites of organophosphate flame retardants: temporal variability and correlations with house dust concentrations
    John D Meeker
    Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan 48109, USA
    Environ Health Perspect 121:580-5. 2013
  6. pmc Predictors of tris(1,3-dichloro-2-propyl) phosphate metabolite in the urine of office workers
    Courtney C Carignan
    Department of Environmental Health, Boston University School of Public Health, 715 Albany Street, Boston, MA 02118, United States
    Environ Int 55:56-61. 2013
  7. pmc 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
    Wu Dong
    Nicholas School of the Environment, Duke University, Durham, NC 27708, United States
    Aquat Toxicol 132:190-9. 2013
  8. pmc Investigating a novel flame retardant known as V6: measurements in baby products, house dust, and car dust
    Mingliang Fang
    Nicholas School of the Environment, Duke University, Durham, North Carolina 27708, USA
    Environ Sci Technol 47:4449-54. 2013
  9. pmc Low level exposure to the flame retardant BDE-209 reduces thyroid hormone levels and disrupts thyroid signaling in fathead minnows
    Pamela D Noyes
    Nicholas School of the Environment, Duke University, Durham, North Carolina, United States
    Environ Sci Technol 47:10012-21. 2013
  10. pmc Inhibition of thyroid hormone sulfotransferase activity by brominated flame retardants and halogenated phenolics
    Craig M Butt
    Nicholas School of the Environment, Duke University, Durham, North Carolina 27708, United States
    Chem Res Toxicol 26:1692-702. 2013

Scientific Experts

  • H M Stapleton
  • J D Meeker
  • Pamela D Noyes
  • Simon C Roberts
  • Ellen M Cooper
  • Courtney C Carignan
  • Craig M Butt
  • Paula I Johnson
  • Jonathan S Bearr
  • Sean C Lema
  • Thomas F Webster
  • Michael D McClean
  • Laura J Macaulay
  • Carys L Mitchelmore
  • Dongli Wang
  • Amanda M Muzzio
  • Mingliang Fang
  • Wu Dong
  • Heather B Patisaul
  • Wendy Heiger-Bernays
  • Valerie McClain
  • Sean P McGee
  • David E Hinton
  • Andreas Sjodin
  • Evan P Gallagher
  • E M Cooper
  • Laura V Dishaw
  • Russ Hauser
  • Deborah J Watkins
  • Robin B Gear
  • Bhramar Mukherjee
  • David Gooden
  • Courtney Carignan
  • Alicia J Fraser
  • Joe Braun
  • Nora K Douglas
  • Colleen Makey
  • Natalie Mabrey
  • Scott M Belcher
  • Kevin W H Kwok
  • Katherine A McCaffrey
  • Fred Tilton
  • David C Volz
  • A Covaci
  • Frederic J Seidler
  • A L N van Nuijs
  • Christina M Powers
  • T F Webster
  • Ian T Ryde
  • Theodore A Slotkin
  • Shannon M Kelly

Detail Information

Publications31

  1. pmc Early zebrafish embryogenesis is susceptible to developmental TDCPP exposure
    Sean P McGee
    Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina 29208, USA
    Environ Health Perspect 120:1585-91. 2012
    ..Chlorinated phosphate esters (CPEs) are widely used as additive flame retardants for low-density polyurethane foams and have frequently been detected at elevated concentrations within indoor environmental media...
  2. pmc Accumulation and endocrine disrupting effects of the flame retardant mixture Firemaster® 550 in rats: an exploratory assessment
    Heather B Patisaul
    Department of Biology, North Carolina State University, Raleigh, NC 27695, USA
    J Biochem Mol Toxicol 27:124-36. 2013
    ..Results of this study are the first to implicate FM 550 as an endocrine disruptor and an obesogen at environmentally relevant levels...
  3. pmc Novel and high volume use flame retardants in US couches reflective of the 2005 PentaBDE phase out
    Heather M Stapleton
    Nicholas School of the Environment, Duke University, Durham, North Carolina, USA
    Environ Sci Technol 46:13432-9. 2012
    ..Given these results, and the potential for human exposure to FRs, health studies should be conducted on the types of FRs identified here...
  4. pmc Associations between brominated flame retardants in house dust and hormone levels in men
    Paula I Johnson
    Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109, USA
    Sci Total Environ 445:177-84. 2013
    ....
  5. pmc Urinary metabolites of organophosphate flame retardants: temporal variability and correlations with house dust concentrations
    John D Meeker
    Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan 48109, USA
    Environ Health Perspect 121:580-5. 2013
    ..Human exposure and health studies of OPFRs are lacking...
  6. pmc Predictors of tris(1,3-dichloro-2-propyl) phosphate metabolite in the urine of office workers
    Courtney C Carignan
    Department of Environmental Health, Boston University School of Public Health, 715 Albany Street, Boston, MA 02118, United States
    Environ Int 55:56-61. 2013
    ..g., polyurethane foam), determine the importance of exposure in other microenvironments such as homes and vehicles, and address the inhalation and dermal exposure pathways...
  7. pmc 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
    Wu Dong
    Nicholas School of the Environment, Duke University, Durham, NC 27708, United States
    Aquat Toxicol 132:190-9. 2013
    ..Our results demonstrate effects of OH-BDEs on thyroid regulating gene expression and provide more insight into potential sites of injury during early life stages...
  8. pmc Investigating a novel flame retardant known as V6: measurements in baby products, house dust, and car dust
    Mingliang Fang
    Nicholas School of the Environment, Duke University, Durham, North Carolina 27708, USA
    Environ Sci Technol 47:4449-54. 2013
    ..A significant correlation was also observed between V6 and TCEP in the dust samples suggesting that the use of V6 is a significant source of TCEP in the indoor environment...
  9. pmc Low level exposure to the flame retardant BDE-209 reduces thyroid hormone levels and disrupts thyroid signaling in fathead minnows
    Pamela D Noyes
    Nicholas School of the Environment, Duke University, Durham, North Carolina, United States
    Environ Sci Technol 47:10012-21. 2013
    ..Declines in the gonadal-somatic index (GSI) and increased mortality were also measured. Effects at the low dose were consistent with the high dose, suggesting nonlinear relationships between BDE-209 exposures and thyroid dysfunction. ..
  10. pmc Inhibition of thyroid hormone sulfotransferase activity by brominated flame retardants and halogenated phenolics
    Craig M Butt
    Nicholas School of the Environment, Duke University, Durham, North Carolina 27708, United States
    Chem Res Toxicol 26:1692-702. 2013
    ..This study suggests that some HOCs, including antimicrobial chemicals and metabolites of flame retardants, may interfere with TH regulation through inhibition of sulfotransferase activity. ..
  11. pmc Tissue distribution and thyroid hormone effects on mRNA abundance for membrane transporters Mct8, Mct10, and organic anion-transporting polypeptides (Oatps) in a teleost fish
    Amanda M Muzzio
    Biological Sciences Department, Center for Coastal Marine Sciences, California Polytechnic State University, San Luis Obispo, CA, USA
    Comp Biochem Physiol A Mol Integr Physiol 167:77-89. 2014
    ..As a whole, these results provide evidence that TH status influences the transcriptional dynamics of mct8, mct10 and several Oatp genes including oatp1c1 in teleost fish. ..
  12. pmc Flame retardant exposure among collegiate United States gymnasts
    Courtney C Carignan
    Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts 02118, United States
    Environ Sci Technol 47:13848-56. 2013
    ....
  13. pmc Rapid method for the measurement of circulating thyroid hormones in low volumes of teleost fish plasma by LC-ESI/MS/MS
    Pamela D Noyes
    Nicholas School of the Environment, Duke University, Box 90328, Durham, NC, 2770, USA
    Anal Bioanal Chem 406:715-26. 2014
    ..Overall, a sensitive and reproducible method was established that takes advantage of LC/MS/MS techniques to rapidly measure TT4 and TT3 with negligible interferences in low volumes of plasma across a variety of teleost fishes. ..
  14. pmc Species specific differences in the in vitro metabolism of the flame retardant mixture, Firemaster® BZ-54
    Jonathan S Bearr
    University of Maryland Baltimore, Baltimore, MD, United States
    Aquat Toxicol 124:41-7. 2012
    ..It can be concluded that a broad range of species are capable of metabolizing TBB and TBPH to various metabolites and further research should be carried out to ascertain the specific products formed from metabolism of TBB and TBPH...
  15. pmc Serum PBDEs in a North Carolina toddler cohort: associations with handwipes, house dust, and socioeconomic variables
    Heather M Stapleton
    Nicholas School of the Environment, Duke University, Durham, North Carolina 27708, USA
    Environ Health Perspect 120:1049-54. 2012
    ..Polybrominated diphenyl ethers (PBDEs) are persistent, bioaccumulative, and endocrine-disrupting chemicals...
  16. pmc In vitro metabolism of the brominated flame retardants 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB) and bis(2-ethylhexyl) 2,3,4,5-tetrabromophthalate (TBPH) in human and rat tissues
    Simon C Roberts
    Nicholas School of the Environment, Duke University, Durham, NC 27708, USA
    Chem Res Toxicol 25:1435-41. 2012
    ....
  17. pmc Characterizing the in vitro hepatic biotransformation of the flame retardant BDE 99 by common carp
    Pamela D Noyes
    Duke University, Nicholas School of the Environment, Integrated Toxicology and Environmental Health Program, Durham, NC, USA
    Aquat Toxicol 97:142-50. 2010
    ..Further studies are needed to evaluate metabolic activity in other species and tissues that contain these enzymes...
  18. pmc House dust concentrations of organophosphate flame retardants in relation to hormone levels and semen quality parameters
    John D Meeker
    Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan 48109, USA
    Environ Health Perspect 118:318-23. 2010
    ..Although widespread human exposure to OP flame retardants is likely, there is a lack of human and animal data on potential health effects...
  19. pmc Analysis of thyroid hormones in serum by liquid chromatography-tandem mass spectrometry
    Dongli Wang
    Nicholas School of the Environment, Duke University, Durham, NC 27708, USA
    Anal Bioanal Chem 397:1831-9. 2010
    ..Development of this method expands the capacity to measure thyroid hormones by including a larger suite of thyroid hormones, and has promising applications for measuring catabolism of thyroid hormones in vitro...
  20. pmc Relationships between polybrominated diphenyl ether concentrations in house dust and serum
    Paula I Johnson
    Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan, USA
    Environ Sci Technol 44:5627-32. 2010
    ..85, p = 0.0005). This study provides evidence that house dust is a primary exposure pathway of PBDEs and supports the use of dust PBDE concentrations as a marker for exposure to PBDE congeners other than BDE 153...
  21. ncbi Accumulation and DNA damage in fathead minnows (Pimephales promelas) exposed to 2 brominated flame-retardant mixtures, Firemaster 550 and Firemaster BZ-54
    Jonathan S Bearr
    University of Maryland Center for Environmental Sciences, Chesapeake Biological Laboratory, Solomons, Maryland 20688, USA
    Environ Toxicol Chem 29:722-9. 2010
    ....
  22. pmc Is the PentaBDE replacement, tris (1,3-dichloro-2-propyl) phosphate (TDCPP), a developmental neurotoxicant? Studies in PC12 cells
    Laura V Dishaw
    Nicholas School of the Environment, Duke University, Durham, NC 27708, USA
    Toxicol Appl Pharmacol 256:281-9. 2011
    ..Additionally, these data suggest that OPFRs may affect neurodevelopment with similar or greater potency compared to known and suspected neurotoxicants...
  23. pmc Species-specific differences and structure-activity relationships in the debromination of PBDE congeners in three fish species
    Simon C Roberts
    Nicholas School of the Environment, Duke University, Durham, North Carolina 27708, United States
    Environ Sci Technol 45:1999-2005. 2011
    ..Carp exhibited a preference for meta-deiodination of the thyroid hormone thyroxine, which was consistent with the preference for meta-debromination of PBDEs observed in carp...
  24. pmc Accumulation and debromination of decabromodiphenyl ether (BDE-209) in juvenile fathead minnows (Pimephales promelas) induces thyroid disruption and liver alterations
    Pamela D Noyes
    Nicholas School of the Environment, Duke University, Durham, North Carolina 27708, USA
    Toxicol Sci 122:265-74. 2011
    ..Altogether, these results suggest that juvenile fish may be uniquely susceptible to thyroid disruptors like PBDEs...
  25. pmc Halogenated phenolic contaminants inhibit the in vitro activity of the thyroid-regulating deiodinases in human liver
    Craig M Butt
    Nicholas School of the Environment, Duke University, Durham, North Carolina 27708, USA
    Toxicol Sci 124:339-47. 2011
    ..This study suggests that some halogenated phenolics, including current use compounds such as plastic monomers, flame retardants, and their metabolites, may disrupt TH homeostasis through the inhibition of DI activity in vivo...
  26. pmc Identification of flame retardants in polyurethane foam collected from baby products
    Heather M Stapleton
    Nicholas School of the Environment, Duke University, Durham, North Carolina, USA
    Environ Sci Technol 45:5323-31. 2011
    ..Future studies are therefore warranted to specifically measure infants exposure to these flame retardants from intimate contact with these products and to determine if there are any associated health concerns...
  27. pmc Associations between polybrominated diphenyl ether (PBDE) flame retardants, phenolic metabolites, and thyroid hormones during pregnancy
    Heather M Stapleton
    Nicholas School of the Environment, Duke University, Durham, North Carolina, USA
    Environ Health Perspect 119:1454-9. 2011
    ..Polybrominated diphenyl ethers (PBDEs) are chemical additives used as flame retardants in commercial products. PBDEs are bioaccumulative and persistent and have been linked to several adverse health outcomes...
  28. pmc Analysis of the flame retardant metabolites bis(1,3-dichloro-2-propyl) phosphate (BDCPP) and diphenyl phosphate (DPP) in urine using liquid chromatography-tandem mass spectrometry
    E M Cooper
    Nicholas School of the Environment, Duke University, Durham, NC 27708, USA
    Anal Bioanal Chem 401:2123-32. 2011
    ..The presented method is simple and sufficiently sensitive to detect these FR metabolites in humans and may be applied to future studies to increase our understanding of exposure to and potential health effects from FRs...
  29. pmc BDE 49 and developmental toxicity in zebrafish
    Valerie McClain
    Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98105 6099, USA
    Comp Biochem Physiol C Toxicol Pharmacol 155:253-8. 2012
    ....
  30. pmc Detection of organophosphate flame retardants in furniture foam and U.S. house dust
    Heather M Stapleton
    Nicholas School of the Environment, Duke University, Durham, North Carolina, USA
    Environ Sci Technol 43:7490-5. 2009
    ..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...