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

项目概要/摘要 暴露于环境金属的神经发育毒性的证据越来越多。最近的研究 已经发现神经毒性可能取决于在发育期间金属暴露发生的时间（例如，在 子宫与儿童期），金属对儿童的神经发育有协同的不利影响。我们 研究旨在阐明儿童期环境金属暴露对神经运动功能的作用， 研究神经发育的结果，通过检查累积和互动的关联， 常见的工业金属混合物。F31中的拟议研究将使用以前从 混合元素暴露对公共健康的影响（PHIME）研究，包括720名儿童（年龄10 - 14岁） 在意大利，不同的空气中暴露于铁合金工业污染物。在一位 环境流行病学、神经行为毒理学、接触生物学、 统计方法和化学混合物，Alexa Friedman（PI）建议估计 具有神经运动功能锰、铜、铬和铅的工业相关金属混合物 在多个发展的关键时期。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） 以及一系列评估运动功能的神经心理学测试。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，以及分级变量选择以检查生物标志物选择。这 这项研究将为我们目前对金属与儿童神经运动功能的关系的理解提供信息， 为减少金属接触的有针对性的干预措施提供见解。它还针对几个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， 在关键的发展窗口使用接触数据。

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.