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: 8291305
• 负责人: HEATHER M STAPLETON
• 金额: $ 36.83万
• 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 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8291305
• 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; 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; Hepatocyte; 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; Measurement; Measures; Mediating; Metabolic; Metabolic Biotransformation; Metabolism; Methods; Mission; Modeling; National Institute of Environmental Health Sciences; Neurologic; Newborn Animals; 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; liquid chromatography mass spectrometry; 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品多溴联苯醚(PBDEs)是一种持久性和普遍存在的污染物，特别是在室内环境中。人体生物监测研究表明，美国人口中的多溴二苯醚水平比测量的任何其他地区，包括欧洲其他工业化国家高出一个数量级以上。此外，由于胎盘转移、母乳摄入和不经意的粉尘摄入，0-4岁的儿童预计会有最高的多溴二苯醚暴露和身体负担。儿童的暴露是令人担忧的，因为使用动物模型的实验室研究发现，多溴二苯醚对甲状腺激素稳态有负面影响，相对于成年动物，这种影响在新生动物中更为明显。这项拟议研究的中心假设是，美国儿童因无意中摄入粉尘而接触到更多的多溴二苯醚，导致对甲状腺激素调节的不利影响。本研究的目的有三个方面：1)测量儿童(1-4岁)对室内粉尘中多溴二苯醚的暴露，测定手与嘴接触的摄入量，并测量这些儿童血清中多溴二苯醚的水平；2)测定多溴二苯醚的肝脏代谢产物；3)确定多溴二苯醚及其代谢产物对细胞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。通过体外实验，研究了PBDEs及其代谢产物对细胞内甲状腺激素水平、脱碘酶(DI)活性、甲状腺调节基因的mRNA表达以及与甲状腺结合球蛋白的特异性结合的影响。首席研究员还计划开发和验证一种新的方法，使用LC/MS-MS(LC/MS-MS)来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，而不是更传统的方法中使用的放射性标记同位素。这种方法可以作为一种筛选工具，用于评估化学物质对DI酶介导的细胞内甲状腺调节的影响。从该项目收集的数据将增加对多溴联苯醚对甲状腺激素调节的影响的了解，并有助于了解暴露在室内环境中的阻燃化学品对儿童发育健康的风险。