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

儿童接触阻燃剂：对甲状腺激素调节的影响

• 批准号: 7674010
• 负责人: HEATHER M STAPLETON
• 金额: $ 48.97万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-15 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7674010
• 关键词: Address; Adult; Adverse effects; Age; Air; Animal Model; Area; Binding; Biological Assay; Biological Monitoring; Blood specimen; Body Burden; Carpet; Cell Culture Techniques; Chemicals; Child; Data; Developed Countries; Developing Countries; Development; Diet; Dust; Environment; Environmental Exposure; Enzymes; Epidemiology; Europe; European Union; Exposure to; Flame Retardants; Floor; Furniture; Genes; Globulins; Growth and Development function; Hand; Health; Hepatic; Home environment; Homeostasis; House Dust; Household Products; Human; Human Milk; In Vitro; Individual; Ingestion; Investigation; Iodide Peroxidase; Isotope Labeling; Laboratory Animals; Laboratory Study; Liquid Chromatography; Liver; Measurement; Measures; Mediating; Metabolic; Metabolic Biotransformation; Metabolism; Methods; Mission; Modeling; National Institute of Environmental Health Sciences; Neurologic; Newborn Animals; Newborn Infant; North Carolina; Oral cavity; Parents; Pathway interactions; Pesticides; Phase; Physiological; Polychlorinated Biphenyls; Population; Principal Investigator; Radio; Recruitment Activity; Regulation; Relative (related person); Research; Risk; Route; Sampling; Screening procedure; Serum; Study models; Thyroid Gland; Thyroid Hormones; Toxic effect; United States; base; brain cell; enzyme activity; hormone regulation; in vitro Assay; juvenile animal; mRNA Expression; phenyl ether; placental transfer; pollutant; research study; stable isotope; tandem mass spectrometry; tool

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.

描述（由申请人提供） 儿童接触阻燃剂：对甲状腺激素调节的影响。阻燃化学物质聚溴二苯基醚（PBDES）是持久和无处不在的污染物，尤其是在室内环境中。人类的生物监测研究表明，相对于任何其他所测量的地区，包括欧洲其他工业化国家，PBDE的水平在美国人口中的水平高于一个数量级。此外，由于胎盘转移，摄入母乳和无意中的粉尘摄入，预计0-4岁之间的儿童的暴露量最高，并且PBDES的体重最高。儿童的暴露引起了人们的关注，因为使用动物模型的实验室研究发现，PBDE对甲状腺激素稳态产生负面影响，甲状腺激素稳态相对于成年人而言，这在新生动物中更为明显。这项拟议的研究的中心假设是，美国的儿童正在从无意间摄入的PBDES接触到更多的PBDE，从而导致对甲状腺激素调节的不利影响。这项研究的目标是三倍：1）测量儿童（1-4岁）暴露于室内灰尘中的PBDES，确定从手接触到口腔接触的摄入率，并测量这些儿童的PBDES水平； 2）确定PBDES的肝代谢产物； 3）确定PBDE及其代谢物对甲状腺内和细胞外甲状腺激素调节的影响，以阐明甲状腺毒性的作用机制。使用体外测定将进行以下研究：PBDE及其代谢物对细胞内甲状腺激素水平，去碘酶（DI）酶活性，甲状腺调节基因的mRNA表达以及特异性结合与甲状腺结合球蛋白的影响。首席研究者还计划使用液相色谱串联质谱法（LC/MS-MS）来开发和验证一种新方法，以测量甲状腺激素水平和DI活性，该方法将使用稳定的同位素而不是用于更传统方法的无线电标记同位素。然后，该方法可以用作评估化学物质对二酶介导的细胞内甲状腺调节作用的筛查工具。从该项目中收集的数据将增加对PBDE对甲状腺激素调节的影响的理解，并有助于理解儿童在室内环境中暴露于阻燃化学物质会对儿童的发育健康风险。