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.

项目摘要 州和联邦机构为消费产品设定了可燃性要求，从而增加了 在家具，纺织品，电子产品和其他产品中的阻燃化学物质的阻燃化学物质 世界各地。有机磷酸盐阻燃剂（OPES）的生产量急剧 近年来，由于神经毒性多溴二苯基（PBDE）火焰的逐步逐渐增加 阻碍化学物质。 OPE的代谢物在77-90％的美国成年人的生物样品中可检测到 暴露主要是通过意外摄入的意外发生。对健康的开始缺乏研究 暴露于这些替代火焰阻燃剂的后果，但它们与神经行为有关 动物的毒性和甲状腺赛酮破坏。妊娠期间和早期的甲状腺赛酮调节 童年对于正常的大脑发育至关重要，其他人则推测甲状腺破坏可能是 OPES引起神经毒性的一种机制。关于OPE的后果的研究很少 人类暴露，儿童或纵向人群中没有暴露。我们打算用 建议的工作。我们的总体假设是，妊娠期间和幼儿期间接触opes是 与甲状腺激素破坏，儿童智力下降和增加的多动症行为有关。目标 1，我们将在几个时间点与OPES的暴露与甲状腺功能之间的关联 孩子们。在AIM 2中，我们将研究OPE暴露与儿童智力与ADHD症状之间的联系， 包括调解分析以确定甲状腺功能是否在于该因果途径上。最后，目标3 将涉及对OPES，PBDES和LEAD的组合的混合分析以及结果 儿童智力。为了实现这些目标，我们将利用良好的预期怀孕和出生 大辛辛那提地区的队列 - 家庭研究（n = 410个出生，随访至12岁）。我们 将分析孕妇及其子女的家用灰尘和尿液样本以测量 最多九个时间点接触OP。我们还将检查先前测量的甲状腺激素水平 从物物血液，脐带血和儿童血液中，并吸引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存在 从母亲和儿童样本中衡量，我们将采用五种不同的分析方法来探索 协同互动和对儿童智力结果的共同影响。这个项目将是 首先是系统地探索产前和产后置换火焰的关系 在既定的儿童出生队列中的暴露，TH水平和神经行为。我们化学的结果 混合分析将为这一领域提供其他上下文，并与现实世界设置相关。我们的发现将有所帮助 围绕火焰化学品的公共卫生政策告知公共卫生政策，可以帮助指导环境健康 社区的教育目标。