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

项目总结 州和联邦机构对消费品设定了易燃性要求，导致增加了 家具、纺织品、电子产品和家庭中随处可见的其他产品的阻燃化学物质 环游世界。有机磷阻燃剂(OPE)的生产量急剧增加 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 阻燃剂。在77%-90%的美国成年人的生物样本中可以检测到有机磷农药的代谢物， 接触主要是通过意外摄入粉尘发生的。对健康的研究令人震惊地缺乏 暴露在这些替代阻燃剂中的后果，但它们与神经行为有关 动物的毒性和甲状腺激素紊乱。妊娠期和早期严格的甲状腺激素调节 童年对于正常的大脑发育是必不可少的，其他人推测甲状腺功能紊乱可能是 OPE导致神经毒性的一种机制。关于OPE的后果的研究很少 在人类中暴露，在儿童或纵向队列中没有。我们打算用以下方式来填补这一知识空白 建议的工作。我们的主要假设是，在怀孕和儿童早期接触Opes是 与甲状腺激素紊乱、儿童智力下降和ADHD行为增加有关。在AIM 1，我们将在几个时间点测量暴露于Opes与甲状腺功能之间的关系 孩子们。在目标2中，我们将调查接触OPE与儿童智力和ADHD症状之间的联系， 包括一项中介分析，以确定甲状腺功能是否存在于这一因果途径上。最后，目标3 将涉及接触有机污染物、多溴联苯醚和铅的混合物分析，以及 儿童智力。为了实现这些目标，我们将利用成熟的预期怀孕和分娩 大辛辛那提地区的队列-家庭研究(n=410名新生儿，12岁随访)。我们 将分析储存的家庭灰尘和孕妇及其子女的尿样，以测量 在最多九个时间点暴露于Opes。我们还将检查以前测量的甲状腺激素水平。 从母血、脐带血和儿童血中提取，并利用大量的儿童神经行为数据。 对于化学混合物的分析，血清多溴二苯醚浓度和血铅水平已经 从母婴样本中测量，我们将使用五种不同的分析方法来探索 协同作用和联合作用对儿童智力结果的影响。这个项目将是 一是系统探讨代用阻燃剂产前与产后的关系 在已建立的出生队列中，暴露、TH水平和神经行为。我们的化学物质的结果 混合物分析将为该领域提供额外的背景和与现实世界设置的相关性。我们的发现将对我们有所帮助 向公共卫生政策提供有关阻燃化学品的信息，并可帮助指导环境健康 社区的教育目标。

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.