Exposure to metal mixtures in multiple critical periods of development and adolescent neuromotor function

项目摘要/摘要 越来越多的证据表明，暴露在环境金属中会对神经发育产生毒性。最新研究 已经发现，神经毒性可能取决于发育期间金属暴露发生的时间(例如，在 金属对儿童的神经发育有协同的不利影响。我们的 这项研究旨在阐明儿童环境中金属暴露对神经运动功能的影响，这在很大程度上是 未充分研究的神经发育结果，通过检查累积和交互关联与 常见的工业金属混合物。本F31中提议的研究将使用之前从 混合元素暴露对公共健康的影响(PHIME)研究，由720名儿童(10-14岁)组成 在意大利，空气中暴露于铁合金工业污染物的情况各不相同。在一个人的指导下 环境流行病学、神经行为毒理学、暴露生物学、 统计方法和化学混合物，Alexa Friedman(PI)建议估计 工业上具有神经运动功能的锰、铜、铬和铅的金属混合物 在发展的多个关键时期。我们将评估金属之间的关系，以 代表产前暴露的多种生物标志物(牙齿、头发、指甲、血液、唾液、尿液) 青春期，以及一系列评估运动功能的神经心理测试。我们将使用国家- 最先进的统计方法，包括贝叶斯核机器回归和基于分位数的g- 金属混合物的计算，以及检查生物标记物选择的分级变量选择。这 研究将提供我们目前对金属与儿童神经运动功能和 为减少金属接触提供有针对性的干预措施。它还瞄准了几个NIEHS战略 目标包括研究生活在环境危害附近的社区的共同暴露和创新 在关键的发展窗口中使用暴露数据。

Project Summary/Abstract Evidence for neurodevelopmental toxicity from exposure to environmental metals is mounting. Recent studies have found that neurotoxicity may depend on when during development the metal exposure occurs (e.g., in utero versus childhood) and that metals have synergistic adverse effects on children's neurodevelopment. Our study aims to elucidate the role of childhood environmental metal exposure on neuromotor function, a largely understudied neurodevelopmental outcome, by examining cumulative and interactive associations with a common industrial metal mixture. The proposed research in this F31 will use previously collected data from the Public Health Impact of Mixed Element exposure (PHIME) study, comprised of 720 children (ages 10-14 years) with varied airborne exposure to ferroalloy industry pollutants in Italy. Under the mentorship of a multidisciplinary team of experts in environmental epidemiology, neurobehavioral toxicology, exposure biology, statistical methods and chemical mixtures, Alexa Friedman (PI) proposes to estimate the associations of an industrially relevant metal mixture of manganese, copper, chromium and lead with neuromotor function in multiple critical periods of development. We will evaluate the relationship between metals, measured in multiple biomarkers (teeth, hair, nails, blood, saliva, urine) that represent exposure from the prenatal period through adolescence, and a battery of neuropsychological tests that evaluate motor function. We will use state- of-the-art statistical approaches, including Bayesian Kernel Machine Regression and quantile-based g- computation for metal mixtures, and hierarchical variable selection to examine biomarker selection. This research will inform our current understanding of metal associations with children's neuromotor function and provide insights for targeted interventions to reduce metals exposure. It also targets several NIEHS strategic goals including the study of co-exposures in communities living near environmental hazards and the innovative use of exposure data across critical developmental windows.