Low-level Exposure to Multiple Metals: Effects on Cognition and Behavior

摘要 在世界范围内，数百万儿童暴露在有毒金属中，包括铅(铅)、砷(As)、镉(Cd)、 和锰(Mn)，对它们的健康和发育有重要影响。研究结果表明-- 确定接触单一有毒金属与儿童神经行为缺陷之间的联系。然而， 金属暴露很少单独发生。然而，到目前为止，很少有研究研究相互作用 有毒金属对认知缺陷或行为问题的影响，往往结果喜忧参半。也很少有低于- 多次接触金属对儿童结局的长期影响。因此，数据的稀缺性 方法论上的限制使这一领域无法为保护 儿童和儿科实践。这项研究的长期目标是了解低水平暴露于 多种有毒金属影响儿童和青春期的神经行为结果，确定潜在的 金属对儿童结局的协同效应。拟议研究的目标是确定如何 儿童接触多种金属会通过中间儿童影响特定的认知功能和行为- 胡德。拟议的研究是一项纵向队列研究，将在乌拉圭的蒙得维的亚进行，并建立 基于先前对一年级儿童的研究。这项研究的重点是As、Cd、Mn、Pb，因为这些元素在生物环境中存在 从乌拉圭儿童那里收集的环境和生物样本中具有逻辑相关性的水平。这个 中心假设是，在低暴露范围内，较高浓度的砷、镉、锰和铅 随着时间的推移，个体与较差的认知和行为有关，共同接触这些金属将 对神经行为结果产生相加或相乘的负面影响。这样做的具体目的是 研究目的是：1)描述砷、镉、锰、铅长期接触的趋势和变化；2)特征--铅、镉、锰和铅的接触。 说明人体金属负荷与特定认知功能缺陷之间的关系， 以及3)表征金属与报告和观察到的问题行为的关联程度- 爱奥斯。研究人群将由大约760名儿童组成。这项研究有一个交错的设计，需要：1)研究人员-- 在之前的两项研究(2010-2013年)中被评估为一年级学生的低年级儿童，以及2) 一年级入学和后续的额外儿童队列。头发和血液样本将被采集 每年一次，在一、三、五年级对儿童的认知和行为进行评估。这种方法是创新的- 因为与以前的研究不同，IN使用纵向方法来检查交互作用 在环境中低水平存在的多种金属中，使用特定工艺导向的齿轮- 消极的结果，而不是智商，后者是一种终结性的衡量标准。这一研究具有重要的现实意义。 致力于传达与接触多种有毒金属有关的健康风险及其潜力 为预防或减轻暴露的发展后果的方法作出贡献。

ABSTRACT Worldwide, millions of children are exposed to toxic metals, including lead (Pb), arsenic (As), cadmium (Cd), and manganese (Mn), with important consequences for their health and development. Research findings con- firm the association between exposure to single toxic metals and neurobehavioral deficits in children. However, metal exposures rarely occur in isolation. Nevertheless, few studies to date have examined interactions among toxic metals on cognitive deficits or behavioral problems, often with mixed results. There is also little under- standing of the long-term consequences of multiple metal exposures on child outcomes. Thus, scarcity of data and methodological limitations have kept this field from making sound recommendations for the protection of children and pediatric practice. The long-term goal of this research is to understand how low-level exposure to multiple toxic metals affects neurobehavioral outcomes across childhood and adolescence, identifying potential synergistic effects of metals on children's outcomes. The objective of the proposed study is to determine how children's exposure to multiple metals affects specific cognitive functions and behavior through middle child- hood. The proposed study is a longitudinal cohort study that will take place in Montevideo, Uruguay and builds on previous research in 1st grade children. The study focuses on As, Cd, Mn, Pb because these occur at bio- logically relevant levels in the environment and biological samples collected from the Uruguayan children. The central hypothesis is that within low range of exposures, higher concentrations of As, Cd, Mn and Pb will be individually associated with poorer cognition and behavior over time, and that co-exposure to these metals will produce additive or multiplicative negative effects on neurobehavioral outcomes. The specific aims of this study are to: 1) describe the trends and variability of the long-term exposure to As, Cd, Mn and Pb, 2) charac- terize the extent to which body burden of the metals is associated with deficits in specific cognitive functions, and 3) characterize the extent to which the metals are associated with reported and observed problem behav- iors. The study population will consist of ~760 children. The study has a staggered design, entailing: 1) the fol- low-up of children who had been evaluated as 1st-graders in 2 previous studies (years 2010-2013), and 2) the enrollment in 1st grade and follow-up of additional cohorts of children. Hair and blood samples will be collected yearly, and children's cognition and behavior will be evaluated in 1st, 3rd and 5th grade. This approach is innova- tive because, in contrast to previous studies, in employs a longitudinal approach to examine interactions among multiple metals that occur at low levels in the environment, and employs specific process-oriented cog- nitive outcomes as opposed to IQ, which is a summative measure. This research is significant in its contribu- tion to the communication of health risks associated with exposure to multiple toxic metals, and in its potential contribution to approaches that will prevent or alleviate the developmental consequences of exposure.