The 2020 ESPINA study follow-up Exam: Fungicides, Insecticides, Inflammation and Child Development

2020年ESPINA研究后续考试：杀菌剂、杀虫剂、炎症和儿童发育

基本信息

批准号：
10659041
负责人：
Jose Ricardo Suarez
金额：
$ 57.33万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-18 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10659041
关键词：
Acetylcholinesterase Adolescence Adolescent Affect Age Agriculture Americas Antifungal Agents Azoles Biological Markers Blood CCL2 gene Child Child Development Child Health Cholinesterase Inhibitors Cognition Cognitive County Cytochrome P450 Cytokeratin 18 Data Collection Development Disease Drug Metabolic Detoxication Ecuador Environmental Health Enzymes Epigenetic Process Exposure to Fatty Liver Flowers Food Free Radicals Funding Future Gender Hair Health Hepatotoxicity Human Impairment In Vitro Inflammation Insecticides Interleukin-6 Investigation Link Liver Measurement Measures Mediating Mental Health Methods Microtubules National Institute of Environmental Health Sciences Nerve Degeneration Neurocognition Neurocognitive Neurocognitive Deficit Neurons Organophosphates Outcome Participant Patients Performance Pesticides Pharmaceutical Preparations Physiological Plasma Population Prevention program Process Production Prospective Studies Quinones Recurrence Research Risk Assessment Safety Sales Saliva Sampling Serum Structure TNF gene Technology Testing Time Toxic effect Transaminases United States National Institutes of Health Urine Vascular Endothelium Work agricultural community agricultural pesticide biobank clinical practice cognitive performance cohort developmental toxicity disorder prevention epidemiology study experimental study exposure pathway follow-up fruits and vegetables fungicide individuals with autism spectrum disorder inflammatory marker inhibitor liver inflammation monocyte neurobehavior neurobehavioral neuroinflammation neurotoxic novel pesticide exposure prenatal exposure prospective prospective test pyrethroid study population urinary young adult

项目摘要

The sales of agricultural insecticides have steadily risen in the last 20 years and the use of fungicides have skyrocketed in the last decade. Unfortunately, direct assessments of children's developmental toxicity in relation to commonly used fungicides such as Azoles or Quinone Outside Inhibitors (QoI) are unavailable because methods for their quantification in bio-specimens have only recently been developed. In experimental studies, exposures QoI fungicides, resulted in epigenetic changes related to neuro-inflammation, and higher levels of free-radicals. Azoles, another heavily used fungicide class, have also been linked with liver inflammation and toxicity in-vitro. Azole fungicides share the same structure as azole antifungals used in clinical practice, which are associated with elevations of liver enzymes in up to 20% of patients. Cholinesterase inhibitor insecticide exposures have been associated with short- and long-lasting neurobehavioral/cognitive delays in children associated. Whether continuing exposures to organophosphates or other insecticides such as neonicotinoids or pyrethroids can affect cognition in adolescence is unclear. We propose to conduct a follow-up investigation of adolescent participants (ages 16-21 y, n=535) of the Secondary Pesticide Exposure among Children and Adolescents (ESPINA) study in 2020. This NIH-funded study has examined participants in Pedro Moncayo County, Ecuador since 2008. Pedro Moncayo has one of the highest concentrations of flower plantations in the Americas. The production of flowers involves a disproportionately high use of fungicides. We plan to assess the ongoing and long-term associations of pesticide exposures with neurocognition, and inflammatory markers (systemic, neuro and liver). To our knowledge, this will be the first epidemiologic study of children/adolescents to evaluate health outcomes in relation to fungicide and neonicotinoid exposures. This prospective study capitalizes on existing blood measurements of insecticides in 2016 and acetylcholinesterase in 2008 and 2016. The specific aims are to test the following hypotheses: Urinary metabolites of insecticides in 2016 and 2020 (organophosphates, neonicotinoids, pyrethroids) and fungicides (Azoles, QoI) in 2016 are associated with: 1) higher subclinical markers of systemic and neuro inflammation (CRP, TNF, IL-6, sICAM-1, sVCAM-1, MCP-1, sCD14, sCD163); 2) Pesticides, particularly azole fungicides are associated with subclinical increases in liver inflammation markers: transaminases (AST and ALT) and cytokeratin 18. We will test concurrent and prospective associations with all inflammation markers in 2016-2018; 3) lower neur0-cognitive performance in adolescence. We will test longitudinal associations of fungicides and insecticides with neurocognitive performance, and will contrast such findings across pesticides to evaluate neurotoxic potencies. 4) As an exploratory aim: we will assess mediating or modifying effects of inflammation on pesticide-induced impaired neurobehavioral performance.

在过去的20年中，农业杀虫剂的销量稳步增长，并使用了杀菌剂在过去的十年中飙升。不幸的是，直接评估儿童的发育毒性与常用的杀菌剂（例如偶氮或奎因酮外部抑制剂（QOI））的关系不可用因为直到最近才开发了其在生物特异性中进行定量的方法。在实验中研究，暴露于QOI杀菌剂，导致与神经炎症相关的表观遗传变化，并且更高自由基的水平。 Azoles是另一个大量使用的杀菌剂类别，也已与肝脏联系起来炎症和毒性在体外。氮氮杀菌剂与使用临床实践与多达20％的患者肝酶升高有关。胆碱酯酶抑制剂杀虫剂暴露与短期和持久有关相关儿童的神经行为/认知延迟。是否继续对有机磷酸盐接触或其他杀虫剂（例如新烟碱或拟甲虫素）可能会影响青春期的认知。我们建议对青少年参与者（16-21岁，n = 535岁）进行后续研究儿童和青少年（ESPINA）研究的次生农药暴露于2020年。这项NIH资助研究自2008年以来研究了厄瓜多尔佩德罗·蒙卡约县的参与者。佩德罗·蒙卡约（Pedro Moncayo）拥有其中之一美洲花种植园的最高浓度。花的生产涉及杀菌剂的使用不成比例。我们计划评估持续和长期的关联具有神经认知和炎症标志物（全身，神经和肝脏）的农药暴露。向我们知识，这将是儿童/青少年的首次流行病学研究，以评估健康状况与杀菌剂和新烟碱暴露有关。这项前瞻性研究利用了现有的血液 2016年杀虫剂的测量以及2008年和2016年的乙酰胆碱酯酶。具体目的是检验以下假设：2016年杀虫剂的尿代谢产物和2020年（有机磷酸盐，新烟碱，拟除虫菊酯）和杀菌剂（Azoles，QOI）在2016年相关其中：1）全身和神经炎症的较高亚临床标记（CRP，TNF，IL-6，SICAM-1，SVCAM-1， MCP-1，SCD14，SCD163）; 2）农药，尤其是硫唑杀菌剂与亚临床增加有关肝脏炎症标记：转氨酶（AST和ALT）和细胞角蛋白18。 2016 - 2018年与所有炎症标记的预期关联； 3）降低神经0认知性能在青春期。我们将测试杀菌剂和杀虫剂与神经认知的纵向关联性能，并将对比农药进行对比以评估神经毒性的效果。 4）探索目的：我们将评估炎症对农药诱导的受损的介导或修饰作用神经行为表现。