Assessing Vulnerability of the Adolescent Brain to Organophosphorus Pesticides

描述（由申请人提供）：有机磷（OP）农药在世界各地的农业中广泛使用，使用农药的工人年龄从十几岁的儿童到60多岁的成年人。有令人信服的证据表明，重复的低水平职业和环境农药暴露与成人的神经行为表现缺陷有关。从事农业工作的青少年面临与成年人相同的风险，但他们的风险是否等于或大于成年人尚不清楚。在埃及，人们季节性地雇佣青少年给棉花作物施用杀虫剂。在埃及，棉花作物的农药使用受到严格监管和标准化，主要限于有机磷农药，主要是毒死蜱。这提供了一个独特的机会来检查高度一致的已知OP农药暴露对青少年神经系统的影响，通过神经行为测试来测量。虽然我们有初步证据表明，与对照组相比，埃及成年施药者的皮肤和尿液样本存在暴露，青少年施药者存在神经行为缺陷，但目前尚无青少年的定量暴露数据。此外，尚未确定的是，这些与暴露相关的影响是否会随着每年重复的暴露（在暑期工作中）而累积，以及这些影响是否会在每年的暴露结束后逆转。本应用程序的目的是检查青少年神经系统对OP农药的剂量相关反应，以验证以下假设：(1)反复暴露会产生进行性缺陷(2)任何缺陷都是可逆的。在目标1中，年轻的施药者，16至18岁的青少年，将在整个农药施用季节进行研究，以检查OP农药暴露（尿代谢物、血液胆碱酯酶和皮肤贴[纱布]样本）对神经行为表现的影响。在目标2中，我们将加强和建设Menoufia大学的研究能力，通过对研究方法和效果测量的科学培训，以及旨在培养赠款写作技能的系列研讨会。通过后续R01应用程序的开发，我们将建议评估新的（更有效的）生物标志物，并开发一种经济的培训干预措施，以减少暴露，从而减少农药暴露的任何累积效应，以及这些暴露对埃及青少年的潜在长期影响。公共卫生相关性：本应用程序的目的是检查青少年神经系统对有机磷农药（OPs）的剂量相关反应，以确定反复接触是否会产生进行性缺陷，并确定这种缺陷是否可逆。我们建议在整个农药施用季节对16至18岁的年轻施药者进行研究，并检查OP农药暴露（尿代谢物、血胆碱酯酶和皮肤贴[纱布]样本）对神经行为表现的影响。我们还将扩大Menoufia大学的研究能力，并提交后续R01拨款，以开发一种经济的培训干预措施，减少接触农药，从而大大减少接触农药的累积影响，以及这些接触对埃及青少年的潜在长期影响。

DESCRIPTION (provided by applicant): Organophosphorus (OP) pesticides are used extensively in agriculture throughout the world, and workers who apply pesticides range in age from children in their teens to adults in their 60s. There is compelling evidence that repeated low-level occupational and environmental pesticide exposures are associated with neurobehavioral performance deficits in adults. Adolescents working in agriculture are exposed to the same risks as adults but whether their risk is equivalent to or greater than that of adults is not known. Adolescents in Egypt are hired seasonally to apply pesticides to the cotton crop. The pesticide application to the cotton crop is highly regulated and standardized across Egypt, and is limited primarily to OP pesticides, primarily chlorpyrifos. This provides a unique opportunity to examine the impact of a highly consistent known OP pesticide exposure on the adolescent nervous system as measured by neurobehavioral tests. While we have preliminary evidence of exposures from dermal and urinary samples in adult Egyptian applicators and evidence of neurobehavioral deficits in adolescent applicators compared to controls, there is no quantitative exposure data available in adolescents. Furthermore, what is not established is if these exposure-related effects accumulate with repeated annual exposure (on summer jobs) and if such effects reverse after the exposure ends each year. The goal of this application is to examine the dose-related response of the adolescent nervous system to OP pesticides, to test the hypotheses that (1) repeated exposures produce a progressive deficit and (2) any deficit is reversible. In Aim 1, young applicators, adolescents 16 to 18 years old, will be studied across the pesticide application season to examine the effects of OP pesticide exposure (urinary metabolites, blood cholinesterase, and dermal patch [gauze] samples) on neurobehavioral performance. In Aim 2 we will strengthen and build the research capacity at Menoufia University through scientific training on research methods and measurement of effects, and a seminar series designed to foster grant-writing skills. Through the development of a follow-on R01 application we will propose to evaluate novel (more effective) biomarkers and develop an economical training intervention that can reduce exposures and thus any cumulative effects of pesticide exposure and the potential long-term effects of those exposures in adolescents in Egypt. PUBLIC HEALTH RELEVANCE: The goal of this application is to examine the dose-related response of the adolescent nervous system to organophosporus pesticides (OPs), to determine if repeated exposures produce a progressive deficit and to determine if this deficit is reversible. We propose to study the young applicators, adolescents 16 to 18 years old, across the pesticide application season and examine the effects of OP pesticide exposure (urinary metabolites, blood cholinesterase, and dermal patch [gauze] samples) on neurobehavioral performance. We will also expand the research capacity at Menoufia University and submit a follow-on R01 grant to develop an economical training intervention that can reduce exposures and thus substantially reduce the cumulative effects of pesticide exposure and the potential long-term effects of those exposures in adolescents in Egypt.