Is Low-Level Arsenic Exposure Related to Neurobehavioral Deficits in Children

描述(申请人提供)：全球数百万儿童暴露在其环境中的神经毒性物质中，如砷，这些物质可能会造成不可逆转的智力和行为障碍。在生活在高暴露地区的学童中，认知缺陷通常以智商衡量，这种缺陷与饮用水、尿液和头发中砷浓度较高有关。然而，我们对低水平砷暴露与儿童认知功能和行为的关联程度的了解有限。这种知识上的差距限制了准确的风险评估和与砷暴露相关的健康风险的沟通。长期目标是了解低水平的砷暴露如何影响儿童和青少年的神经行为结果，并确定宿主和环境因素(如年龄、性别、遗传构成、营养状况和其他环境暴露)，这些因素可能会改变砷对儿童认知和行为的影响。该研究的目的是确定低水平砷暴露和砷甲基化能力对6-7岁儿童认知功能和行为的影响。中心假设是，在低暴露范围内，水和尿中砷浓度较高(特别是尿中甲基砷酸的比例较高)将与较差的认知和行为问题有关。两个具体目标是1)确定低水平砷暴露(&lt；50 5g/L)在多大程度上与一年级儿童的神经行为结果相关，以及2)确定低砷甲基化能力在多大程度上损害暴露在AS下的一年级儿童的认知和行为。除了收集新入学儿童的水和尿样外，还将利用乌拉圭蒙得维的亚一年级学生正在进行的一项研究中的存档水和尿样来满足这两个目标。结果来自广泛的 将使用对儿童的神经行为评估以及营养状况和神经毒物暴露的指标。这种方法是创新的，因为与之前的研究不同，它系统地检查了低水平砷暴露和甲基化能力对儿童认知的影响。这些方法学上的进步将导致对砷暴露本身进行更准确的风险评估，并为今后设计对这些问题进行大规模、系统的调查提供重要数据。这项研究在传播与砷暴露相关的健康风险方面具有重要意义。一旦确定了与砷排泄(甲基化)相关的因素，也可以在预防暴露和制定风险调整战略方面取得重要进展。最后，从长远来看，这项研究的意义在于它可能有助于美国等环境中关于砷监测和行动水平的政策，在这些环境中，儿童通常经历低水平的砷暴露。

DESCRIPTION (provided by applicant): Millions of children worldwide are exposed to neurotoxic substances in their environment, such as arsenic, that produce potentially irreversible intellectual and behavioral impairments. Cognitive deficits, most typically measured as IQ in school children living in high-exposure areas, have been associated with higher concentrations of arsenic in drinking water, urine and hair. However, we have limited understanding of the extent to which low- level arsenic exposure is associated with children's cognitive function and behavior. This gap in knowledge limits accurate risk assessment and the communication of health risks associated with arsenic exposure. The long-term goal is to understand how low-level arsenic exposure affects neurobehavioral outcomes across childhood and adolescence, and to identify host and environmental factors (such as age, sex, genetic make- up, nutritional status, and other environmental exposures) that may modify the effects of arsenic on child cognition and behavior. The objective of the proposed study is to determine the effects of low-level arsenic exposure and arsenic methylation capacity on cognitive function and behavior in 6-7 year-old children. The central hypothesis is that within low-range of exposures, higher arsenic concentrations in water and urine (particularly higher fraction of urinary methylarsonic acid) will be associated with poorer cognition and behavior problems. The two specific aims are 1) Determine to what extent low-level arsenic exposure (<50 5g/L) is associated with neurobehavioral outcomes in first-grade children, and 2) Determine to what extent low arsenic methylation capacity impairs cognition and behavior in first-grade children exposed to As. Archived water and urine samples from an ongoing study of first-graders from Montevideo, Uruguay will be utilized to address both aims, in addition to the collection of water and urine samples from newly enrolled children. Results from extensive Neurobehavioral assessments of the children and indicators of nutritional status and neurotoxicant exposure will be employed. This approach is innovative because in contrast to previous studies, it systematically examines the effects of low-level arsenic exposure and methylation capacity on child cognition. These methodological advances will result in more accurate risk-assessment of arsenic exposure on its own and provide important data to inform the design of large, systematic investigations of these issues in the future. This research is significant in its contribution to the communication of health risks associated with arsenic exposure. Important strides toward the prevention of exposure and the development of risk-modification strategies can also be achieved once factors associated with the excretion of arsenic (methylation) are identified. Finally, the significance of this research, over the long-term, lies in its potential contribution to policies on arsenic monitoring and action levels in settings, such as the United States, where children typically experience low-level arsenic exposure.