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，以解决生活在俄克拉荷马州焦油溪超级基金所在地的社区的问题-该地区受到采矿废物中金属（铅，镉，铁，锰等）的高度污染，并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“真实的世界”问题，即，“chat”（采矿废物）中存在的金属混合物在接触、吸收、剂量和对儿童发育的不利影响方面相互作用的可能性。 我们的中心将在四个核心的支持下进行四个研究项目。项目1将是一项以社区为基础的参与性流行病学研究，检查胎儿和幼儿接触金属（铅、锰、镉和铁）的生物标志物，它们对智力发育指标的影响，以及它们对准实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的效用，以表征聊天，进行嵌套的病例对照研究的决定因素，高与低负担的金属之间的儿童参与项目1，并产生标准化的“同质化聊天”项目3和4。项目3将研究金属转运的结合和转运分子的表达，以及金属从肺和肠道到血液、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动物有关。项目4将审查 产前和新生儿暴露于金属对大鼠神经化学变化和神经行为结果的影响。在项目3和项目4中，将金属简单混合物的效果与“均质化聊天”的效果进行比较。项目1将探讨居住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改性影响。 神经毒性也将在项目4中探讨。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，我们的社区外展和翻译核心将利用与基础广泛的社区咨询委员会共同开发的创新外展活动组合，以提高认识和 影响行为和健康习惯，以防止儿童因接触采矿废物中的金属而受到不良健康影响。

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.