Vulnerability of the Adolescent Brain to Organophosphorus Pesticides

青少年大脑对有机磷农药的脆弱性

• 批准号: 9180625
• 负责人: Diane S Rohlman
• 金额: $ 48.7万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-03-04 至 2019-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9180625
• 关键词: Acute; Address; Adolescent; Adult; Agricultural Workers; Agriculture; Animals; Arylesterase; Behavior; Biological; Biological Markers; Blood; Brain; CYP2B6 gene; CYP2C19 gene; Child; Chlorpyrifos; Cholinesterases; Chronic; Data; Dose; Education; Egypt; Environmental and Occupational Exposure; Enzymes; Equipment; Exhibits; Exposure to; Future; Genetic Polymorphism; Gossypium; Grant; Health; Home environment; Human; Hygiene; International; Knowledge; Learning; Long-Term Effects; Longitudinal Studies; Measures; Mentors; Metabolism; Occupational; Occupational Exposure; Outcome; Patient Self-Report; Performance; Pesticides; Pilot Projects; Population; Predisposition; Program Research Project Grants; Randomized Controlled Trials; Reaction; Recovery; Reporting; Research; Research Institute; Seasons; Symptoms; Testing; Time; Training Programs; Universities; Videoconferences; Work; Writing; agricultural community; base; cohort; cypermethrin; design; environmental pesticide exposure; epidemiology study; experience; high risk; neurobehavioral; neurobehavioral test; neurotoxic; neurotoxicity; pesticide exposure; prenatal exposure; public health relevance; pyrethroid; skills; specific biomarkers; trial design; urinary; vulnerable adolescent

DESCRIPTION (provided by applicant): Despite evidence from human and animal studies that clearly identifies neurotoxicity as the primary adverse endpoint; the long-term effects of repeated occupational and environmental exposures to organophosphorus pesticides (OPs) remain poorly understood. There is also a critical need to investigate the susceptibility of children and adolescents to pesticides, since the developing brain may be uniquely sensitive to the neurotoxic effects of these agents. Partnering with colleagues at Egypt's Menoufia University, we conducted a pilot study of adolescents working for the Ministry of Agriculture as pesticide applicators for the cotton crop. Building on these preliminary findings, we propose a longitudinal study to investigate the relationship between sensitive and specific biomarkers of pesticide exposure, effect and susceptibility and multiple measures of neurobehavioral function in this unique cohort over a 5 year period to assess cumulative and potentially reversible effects. Our overarching hypothesis is that the inherent plasticity of the developing adolescent brain will allow recovery from selected neurobehavioral deficits associated with short- and long-term exposures to pesticides. Three aims address this hypothesis, expand on the successful efforts begun in the R21 project, to build research skills at Menoufia and work with the Ministry of Agriculture to identify susceptible populations and put into place appropriate measures to reduce pesticide exposure. Aim 1 will determine the association between pesticide exposure and neurobehavioral function in a longitudinal study among adolescent cohorts with occupational (applicators) or environmental (non-applicators) exposures to test the hypothesis that neurobehavioral performance deficits associated with short-term exposure occur during the application season but that there is recovery of selected neurobehavioral functional domains after the summer spray season ends. Some deficits may persist beyond the spray season or after repeated summer spray seasons. A biologically- based exposure assessment will incorporate levels of urinary metabolites of chlorpyrifos and profenophos (OPs) and alpha-cypermethrin (pyrethroid) and functional polymorphisms in key enzymes involved in OP metabolism (CYP2B6, CYP2C19, and PON1) as modifiers of bioeffective dose. Aim 2 will expand the research capacity at Menoufia University by establishing a Research Institute that will: (a), build epidemiologic research capacity (b) teach grant writing and research skills in shot courses held locally and through videoconferences, (c) provide mentoring and international education experiences, and (d) implement a pilot project research program. This is designed to create a competitive research culture at Menoufia University. Aim 3 will develop a training program for the Ministry of Agriculture workers (including applicators) on ways to reduce exposure through hygiene, behavior (work practice) change and use of protective equipment, addressing both environmental (home) and occupational exposures. A randomized controlled trial design will evaluate the impact of the training program on reaction, behavior, and knowledge (learning and retention).

描述（由申请人提供）：尽管人类和动物研究的证据清楚地将神经毒性识别为主要不利终点；反复的职业和环境暴露于有机磷（OP）的长期影响仍然很少了解。还需要研究儿童和青少年对农药的敏感性，因为发育中的大脑可能对这些药物的神经毒性作用唯一敏感。我们与埃及梅努菲亚大学（Menoufia University）的同事合作，对在农业部工作的青少年进行了试点研究，作为棉花作物的农药施用者。在这些初步发现的基础上，我们提出了一项纵向研究，以研究在这个独特的队列中，在这一独特的队列中，敏感的和特定的农药暴露，效果和敏感性以及多种神经行为功能的措施之间的关系，以评估累积性和潜在可逆效应。 我们的总体假设是，发展中的青少年大脑的固有可塑性将使与短期和长期暴露于农药相关的选定神经行为缺陷中恢复。三个目的解决了这一假设，扩展了R21项目开始的成功努力，以在Menoufia建立研究技能，并与农业部合作，以识别易感人群并采取适当的措施来减少农药暴露。 AIM 1将在青少年组中与职业（施用者）或环境（非申请人）暴露之间的一项纵向研究中的农药暴露与神经行为功能之间的关联，以测试神经行为性能缺陷的假说，即在应用季节中，与所选的NeurobeBobeBobeBobeBobeehavsaviorshavsaviorshavsaviorshavsavior sermant inseplobe neyerave seption short short tembosials相关。某些缺陷可能会超出喷雾季节或反复的夏季喷雾季节。基于生物学的暴露评估将纳入毒性磷酸和pros磷（OPS）和α-胞肽（甲基甲性甲状腺素）的尿尿代谢物水平，以及与OP代谢相关的关键酶（CYP2B6，CYP2B6，CYP2C19，cyp2c19，cyp2c19，cyp2c19，cyp2c19，cyp2c19），均为MODIFERCED涉及的关键酶和功能多态性。 AIM 2将通过建立一家研究所的研究能力来扩大在Menoufia大学的研究能力，该研究所将：（a）建立流行病学研究能力（b）在本地和视频会议上教授的射击课程中教授赠款写作和研究技能，（c）提供指导和国际教育经验，以及（d）实施一项飞行员项目研究计划。这旨在在Menoufia大学创建竞争性的研究文化。 AIM 3将针对农业工人部（包括申请者）制定培训计划，以减少通过卫生，行为（工作实践）更改和使用防护设备，解决环境（家庭）和职业曝光的方法。随机对照试验设计将评估培训计划对反应，行为和知识（学习和保留）的影响。