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

项目摘要 州和联邦机构为消费品设定了易燃性要求， 阻燃化学品的家具，纺织品，电子产品和其他产品无处不在的家庭 世界各地有机磷酸酯阻燃剂（OPES）的生产量急剧增加， 近年来，由于逐步淘汰具有神经毒性的多溴二苯醚（PBDE）火焰， 阻燃化学品在77-90%的美国成年人的生物样品中可检测到OPES的代谢物， 而暴露主要是通过意外摄入灰尘发生的。对人类健康的研究 暴露于这些替代阻燃剂的后果，但它们与神经行为有关。 毒性和甲状腺激素紊乱。妊娠期和妊娠早期甲状腺激素的严格调节 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 OPEs引起神经毒性的一种机制。关于OPE后果的研究很少 人类暴露，儿童或纵向队列中无暴露。我们打算填补这一知识空白， 提议的工作。我们的总体假设是，在妊娠期和幼儿期暴露于OPEs， 与甲状腺激素紊乱、儿童智力下降和ADHD行为增加有关。在aim中 1，我们将测量在几个时间点暴露于OPEs和甲状腺功能之间的关联， 孩子在目标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通路上。最后，目标3 将涉及对接触OPEs、PBDEs和铅的混合物进行分析， 儿童智力。为了实现这些目标，我们将利用一个良好的前瞻性怀孕和分娩 大辛辛那提地区的队列-HOME研究（n=410例出生，随访至12岁）。我们 将分析储存的家庭灰尘和孕妇及其子女的尿液样本， 在多达9个时间点暴露于OPEs。我们还将检查先前测量的甲状腺激素水平 从母亲的血液，脐带血，和儿童的血液，并借鉴了广泛的电池儿童神经行为数据。 在化学混合物分析方面， 我们将采用五种不同的分析方法来探索 协同作用和联合效应对儿童智力的结果。该项目将成为 首次系统地探讨了产前和产后更换阻燃剂的关系 已确定的儿童出生队列中的暴露、TH水平和神经行为。我们的化学测试结果 混合物分析将为这一领域提供额外的背景和现实世界的相关性。我们的研究结果将有助于 告知有关阻燃化学品的公共卫生政策，并有助于指导环境卫生 社区教育目标。

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.