Assessing early-life exposure to replacement flame retardant chemicals and associations with thyroid disruption and altered neurobehavioral function in a longitudinal birth cohort

在纵向出生队列中评估生命早期接触替代阻燃化学品的情况以及与甲状腺破坏和神经行为功能改变的关系

• 批准号: 10448250
• 负责人: Zana Percy
• 金额: $ 4.42万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10448250
• 关键词: 12 year old; 3 year old; 8 year old; Adult; Affect; Age; Animals; Area; Attention deficit hyperactivity disorder; Behavior; Behavior Disorders; Behavior assessment; Biological; Birth; Blood; Brain; Chemical Exposure; Chemicals; Child; Childhood; Cognition; Communities; Data; Development; Dose; Dust; Electronics; Endocrine; Endocrine Disruptors; Environment; Environmental Health; Equation; Esters; Exposure to; Flame Retardants; Furniture; Goals; Government; Hand; Health; Health Policy; Home; Hormones; House Dust; Human; Ingestion; Intelligence; Joints; Knowledge; Lead; Lead levels; Link; Longitudinal cohort; Measurement; Measures; Mediation; Modeling; Oral cavity; Organophosphates; Outcome; Outcome Measure; Pathway interactions; Pattern; Phase; Predisposition; Pregnancy; Pregnant Women; Production; Property; Public Health; Research; Route; Sampling; Series; Serum; Source; Statistical Methods; Symptoms; System; Testing; Textiles; Thyroid Function Tests; Thyroid Hormones; Thyrotropin; Thyroxine; Time; Toxic Environmental Substances; Toxic effect; Toxicology; Triiodothyronine; Umbilical Cord Blood; United States; Urine; Woman; Work; analytical method; blood lead; chemical association; child battery; cohort; consumer product; developmental neurotoxicity; early childhood; early life exposure; exposed human population; follow-up; hormone regulation; in vivo; insight; neurobehavior; neurobehavioral; neurotoxic; neurotoxicity; polybrominated diphenyl ether; postnatal; prospective; response; thyroid disruption

PROJECT SUMMARY Flammability requirements are set for consumer products by state and federal agencies, resulting in the addition of flame retardant chemicals to furniture, textiles, electronics, and other products found ubiquitously in homes around the world. The production volumes of organophosphate flame retardants (OPES) have drastically increased in recent years due to the phase-out of the neurotoxic polybrominated diphenyl ether (PBDE) flame retardant chemicals. The metabolites of OPES are detectable in biological samples of 77-90% of U.S. adults, and exposure occurs mainly through accidental dust ingestion. There is a startling lack of research into the health consequences of exposure to these replacement flame retardants, but they have been linked to neurobehavioral toxicity and thyroid hormone disruption in animals. Tight thyroid hormone regulation during gestation and early childhood is essential for normal brain development, and others have speculated that thyroid disruption may be one mechanism by which OPEs cause neurotoxicity. There is very little research on the consequences of OPE exposure in humans, and none in children or longitudinal cohorts. We intend to fill this knowledge gap with the proposed work. Our overarching hypothesis is that exposure to OPEs during gestation and early childhood is associated with thyroid hormone disruption, decreased child intelligence, and increased ADHD behaviors. In aim 1, we will measure the association between exposure to OPEs at several time points and thyroid function in children. In aim 2, we will investigate the link between OPE exposure and child intelligence and ADHD symptoms, including a mediation analysis to determine whether thyroid function lies on this causal pathway. Finally, aim 3 will involve a mixtures analysis of exposure to a combination of OPEs, PBDEs, and lead and the outcome of child intelligence. To accomplish these aims, we will utilize a well-established prospective pregnancy and birth cohort in the Greater Cincinnati area—the HOME Study (n=410 births with follow-up to 12 years of age). We will analyze stored household dust and urine samples from pregnant women and their children to measure exposure to OPEs at up to nine time-points. We will also examine previously measured thyroid hormone levels from maternal blood, cord blood, and child blood and draw on an extensive battery of child neurobehavioral data. For the chemical mixtures analysis, serum PBDE concentrations and blood lead levels have already been measured from maternal and child samples, and we will employ five different analytical methods to explore synergistic interactions and joint effects on the outcome of child intelligence. This project will be the among the first to systematically explore the relationship between pre- and post-natal replacement flame retardant exposure, TH levels, and neurobehavior in an established birth cohort of children. The results of our chemical mixtures analysis will give this field additional context and relevance to real-world settings. Our findings will help inform public health policy around flame retardant chemicals and could help guide environmental health educational goals for communities.

项目概要 州和联邦机构为消费品设定了可燃性要求，因此增加了 将阻燃化学品应用于家具、纺织品、电子产品和其他家庭中随处可见的产品 有机磷酸酯阻燃剂 (OPES) 的产量非常惊人。 近年来由于神经毒性多溴二苯醚 (PBDE) 火焰的逐步淘汰而增加 77-90% 的美国成年人的生物样本中可检测到 OPES 的代谢物， 接触主要是通过意外摄入灰尘而引起的，但对健康的研究却严重缺乏。 接触这些替代阻燃剂的后果，但它们与神经行为有关 动物妊娠期间和早期的毒性和甲状腺激素干扰。 童年对于正常的大脑发育至关重要，其他人推测甲状腺功能紊乱可能与 OPE 引起神经毒性的一种机制 关于 OPE 后果的研究很少。 我们打算用以下方法来填补这一知识空白： 我们提出的工作的总体假设是，在妊娠期和幼儿期接触 OPE 是可能的。 与甲状腺激素紊乱、儿童智力下降和多动症行为增加有关。 1，我们将测量几个时间点暴露于 OPE 与甲状腺功能之间的关联 在目标 2 中，我们将调查 OPE 暴露与儿童智力和 ADHD 症状之间的联系， 包括中介分析以确定甲状腺功能是否位于该因果路径上。最后，目标 3。 将涉及对 OPE、PBDE 和铅的组合暴露进行混合物分析以及结果 为了实现这些目标，我们将利用完善的预期怀孕和分娩。 大辛辛那提地区的队列——HOME 研究（n = 410 名新生儿，随访至 12 岁）。 将分析孕妇及其孩子储存的家庭灰尘和尿液样本，以进行测量 我们还将检查之前测量的甲状腺激素水平。 从母血、脐带血和儿童血液中提取，并利用大量儿童神经行为数据。 对于化学混合物分析，血清 PBDE 浓度和血铅水平已经 从母婴样本中进行测量，我们将采用五种不同的分析方法来探索 该项目将是对儿童智力成果的协同相互作用和共同影响。 首次系统探讨产前和产后替代阻燃剂之间的关系 我们的化学物质的结果。 混合物分析将为该领域提供更多背景信息以及与现实世界环境的相关性，我们的研究结果将有所帮助。 为有关阻燃化学品的公共卫生政策提供信息，并有助于指导环境健康 社区的教育目标。