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

描述（由申请人提供）：全世界有数百万儿童暴露于环境中的神经毒性物质，如砷，这些物质可能会产生不可逆的智力和行为障碍。认知缺陷，最典型的是生活在高暴露地区的学龄儿童的智商，与饮用水，尿液和头发中较高浓度的砷有关。然而，我们对低水平砷暴露与儿童认知功能和行为的关系了解有限。这一知识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砷暴露如何影响儿童和青少年的神经行为结果，并确定可能改变砷对儿童认知和行为影响的宿主和环境因素（如年龄，性别，遗传组成，营养状况和其他环境暴露）。本研究的目的是探讨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，在低范围的暴露，水和尿中较高的砷浓度（特别是较高的尿甲基胂酸分数）将与较差的认知和行为问题。两个具体目标是：1）确定低水平砷暴露（<50 5g/L）与一年级儿童神经行为结果的相关程度; 2）确定低砷甲基化能力在多大程度上损害了一年级儿童的认知和行为。除了收集新入学儿童的水样和尿样外，还将利用对乌拉圭蒙得维的亚一年级学生进行的一项正在进行的研究的存档水样和尿样来实现这两个目标。结果广泛 将采用儿童神经行为评估以及营养状况和神经毒物暴露指标。这种方法是创新的，因为与以前的研究相比，它系统地研究了低水平砷暴露和甲基化能力对儿童认知的影响。这些方法上的进步将导致更准确的风险评估砷暴露本身，并提供重要的数据，告知设计的大，系统的调查，这些问题在未来。这项研究是显着的贡献，与砷暴露相关的健康风险的沟通。一旦确定了与砷排泄（甲基化）相关的因素，也可以实现预防暴露和制定风险调整策略的重要进展。最后，这项研究的意义，从长远来看，在于其潜在的贡献砷监测和行动水平的设置，如美国，儿童通常经历低水平的砷暴露的政策。

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.