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明确表明神经毒性是主要不良终点；反复职业和环境接触有机磷农药 (OP) 的长期影响仍知之甚少。还迫切需要调查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剂的神经毒性作用特别敏感。我们与埃及梅努菲亚大学的同事合作，对在农业部担任棉花作物杀虫剂工作的青少年进行了一项试点研究。基于这些初步发现，我们提出了一项纵向研究，以调查农药暴露、效应和敏感性的敏感和特定生物标志物之间的关系，以及这个独特队列中神经行为功能的多种测量指标在 5 年的时间里，以评估累积和潜在可逆的影响。 我们的总体假设是，发育中的青少年大脑固有的可塑性将使与短期和长期接触农药相关的特定神经行为缺陷得以恢复。三个目标解决了这一假设：扩大 R21 项目开始的成功努力，在 Menoufia 建立研究技能，并与农业部合作确定易感人群并采取适当措施减少农药接触。目标 1 将在职业（施用者）或环境（非施用者）暴露的青少年队列中进行纵向研究，确定农药暴露与神经行为功能之间的关联，以检验施用期间发生与短期暴露相关的神经行为表现缺陷的假设但在夏季喷雾季节结束后，选定的神经行为功能域会恢复。一些缺陷可能会在喷雾季节过后或重复的夏季喷雾季节之后持续存在。基于生物学的暴露评估将纳入毒死蜱和丙溴磷 (OP) 和甲氯氰菊酯 (拟除虫菊酯) 的尿代谢物水平以及参与 OP 代谢的关键酶（CYP2B6、CYP2C19 和 PON1）的功能多态性，作为生物有效剂量的调节剂。目标 2 将通过建立一个研究所来扩大梅努菲亚大学的研究能力，该研究所将：(a) 建立流行病学研究能力，(b) 在当地举办的短期课程中和通过视频会议教授拨款写作和研究技能，(c) 提供指导和国际教育经验，以及 (d) 实施试点项目研究计划。这样做的目的是为了在梅努菲亚大学创造一种有竞争力的研究文化。目标 3 将为农业部工作人员（包括施用人员）制定一项培训计划，介绍如何通过卫生、行为（工作实践）改变和使用防护设备来减少接触，同时解决环境（家庭）和职业接触问题。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。