METAL MIXTURES AND CHILDREN'S HEALTH

我们建议建立一个儿童环境健康和疾病预防研究中心，以解决俄克拉荷马州焦油溪超级基金遗址的一个社区的关切-该地区受到采矿废物中金属(铅、镉、铁、锰和其他)的高度污染，居住着许多美洲原住民后裔。我们的总体目标是采取高度创新和综合的方法来解决“现实世界”问题，即“CHAT”(采矿废物)中存在的金属混合物在暴露、吸收、剂量和对儿童发育的不利影响方面相互作用的潜力。 我们的中心将在四个核心的支持下开展四个研究项目。项目1将是一项以社区为基础的参与性流行病学研究，检查胎儿和儿童早期接触金属(铅、锰、镉和铁)的生物标记物，它们对智力发展指标的影响，以及它们对准试验性随机试验的反应。 营养和行为干预。项目2将评估大小分级和顺序提取研究在确定ChAT特征方面的作用，对参与项目1的儿童中金属负荷高低的决定因素进行嵌套病例对照研究，并为项目3和4制作标准化的“均质Chat”。项目3将调查金属运输结合和转运分子的表达，以及金属从肺和肠道进入血液、中枢神经系统和其他器官的相应药代动力学，因为它们与怀孕大鼠及其断奶有关。项目4将研究 出生前和出生后接触金属对大鼠神经化学变化和神经行为结局的影响。在项目3和项目4中，简单金属混合物的效果将与“均质化ChAT”的效果进行比较。项目1将探讨生活在有毒废物附近的压力的潜在影响，以及压力对金属的潜在调节作用 项目4还将探讨神经毒性。我们的行政、分析化学和生物统计学核心将使我们能够充分整合和支持我们的研究，我们的社区外联和翻译核心将利用与基础广泛的社区咨询委员会一起开发的一系列创新的外联活动来提高认识和 影响行为和健康做法，以防止儿童接触采矿废物中的金属对健康造成不利影响。

We propose to establish a Center for Children's Environmental Health and Disease Prevention Research that addresses the concerns of a community living in the Tar Creek Superfund site of Oklahoma - an area highly contaminated by metals (lead, cadmium, iron, manganese, and others) in mining waste and populated by many residents of Native American descent. Our overall goal is to take a highly innovative and integrated approach to addressing a "real world" problem, i.e., the potential of the mixtures of metals that are present in "chat" (mining waste) to interact with each other in terms of exposure, absorption, dose, and adverse effects on the development of children. Our Center will pursue four Research Projects with the support of four Cores. Project 1 will be a community-based participatory epidemiologic study that examines biological markers of fetal and early childhood exposure to metals (lead, manganese, cadmium, and iron), their impact on measures of mental development, and their response to a quasi-experimental randomized trial of nutritional and behavioral interventions. Project 2 will assess the utility of size fractionation and sequential extraction studies for characterizing chat, conduct a nested case-control study of the determinants of high versus low burdens of metals amongst children participating in Project 1, and produce standardized "homogenized chat" for Projects 3 and 4. Project 3 will investigate the expression of binding and transporter molecules for metal transport and the corresponding pharmacokinetics of metals from the lung and gut to the blood, CNS and other organs as they relate to pregnant rats and their weanlings. Project 4 will examine the effect of pre- and neo-natal exposure to metals on neurochemical changes and neurobehavioral outcomes in rats. The effect of simple mixtures of metals will be compared with the effect of "homogenized chat" in both Projects 3 and 4. The potential effect of stress from living near toxic waste will be explored in Project 1 and the potential modifying effect of stress on metals neurotoxicity will also be explored in Project 4. Our Administrative, Analytical Chemistry, and Biostatistics Cores will enable us to fully integrate and support our research, and our Community Outreach and Translation Core will utilize an innovative portfolio of outreach activities developed in conjunction with a broadly-based Community Advisory Board to develop awareness and influence behaviors and health practices in order to prevent adverse health effects in children from exposure to metals in mining waste.