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

描述（由申请人提供）：全世界数以百万计的儿童暴露于环境中的神经毒性物质，如砷，这些物质会产生潜在的不可逆转的智力和行为障碍。认知缺陷与饮用水、尿液和头发中砷的浓度较高有关。认知缺陷最典型的衡量标准是生活在高砷暴露地区的学龄儿童的智商。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了解有限。这方面的知识差距限制了准确的风险评估和与砷接触有关的健康风险的交流。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、基因组成、营养状况和其他环境暴露）。本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，水和尿液中较高的砷浓度（特别是较高比例的尿甲基胂酸）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（<50 5g/L）与一年级儿童神经行为结果的关联程度；2)确定低砷甲基化能力在多大程度上损害一年级暴露于砷的儿童的认知和行为。除了收集新入组儿童的水和尿样外，还将利用乌拉圭蒙得维的亚一年级小学生的存档水和尿样来实现这两个目标。广泛的结果

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. PUBLIC HEALTH RELEVANCE: The proposed research is relevant to public health because the characterization of the cognitive/behavioral effects of low-level arsenic exposure in children will result in more accurate communication of health risks in pediatric populations and the identification of appropriate prevention or intervention strategies. This research is relevant to the mission of the NIEHS through its contribution of fundamental knowledge that will reduce the burden of human disability by understanding environmental influences on disease development.