Assess the Effects of Pre- and Postnatal exposure to the organophosphorus

评估产前和产后接触有机磷的影响

• 批准号: 7584733
• 负责人: Virginia A Rauh
• 金额: $ 56.7万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-11 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7584733
• 关键词: 10 year old; 3 year old; 9 year old; Adverse effects; Affect; Agriculture; Air Pollutants; Anatomy; Animal Model; Animals; Area; Attention; Attention deficit hyperactivity disorder; Behavioral; Biological Markers; Birth Weight; Brain; Brain Chemistry; Brain region; Chemicals; Child; Child Development; Chlorpyrifos; Clinical; Cognition; Cognitive; Cohort Studies; Development; Developmental Delay Disorders; Diagnosis; Diazinon; Diffusion Magnetic Resonance Imaging; Documentation; Dose; Environmental Health; Exposure to; Fetal Growth; Fiber; Head; Health; Hippocampus (Brain); Hyperactive behavior; Image; Lateral; Literature; Longitudinal Studies; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; Memory; Metabolism; Modeling; Motor; Motor Activity; N-acetylaspartate; National Institute of Environmental Health Sciences; Neurobiology; Neurons; Neuropsychological Tests; Organophosphates; Parietal; Pattern; Performance; Pesticides; Problem behavior; Regression Analysis; Relative (related person); Safety; Sensorimotor functions; Sensory; Severities; Structure; Subgroup; Symptoms; TNFRSF5 gene; Temporal Lobe; Translational Research; Umbilical Cord Blood; United States; Work; association cortex; base; brain size; brain volume; cognitive function; cohort; depression; early childhood; inattention; indexing; inner city; neurobehavioral; neurodevelopment; neuroimaging; neuropsychological; postnatal; prenatal; prenatal exposure; prospective; psychologic; public health relevance; relating to nervous system; respiratory; response; toxic organophosphate insecticide exposure; white matter

DESCRIPTION (provided by applicant): The purpose of this study is to assess the effects of pre- and postnatal exposure to the organophosphorus (OP) pesticide chlorpyrifos (CPF) on neurobehavioral functioning in a cohort of inner-city children who have reached 9 years of age. This work builds on, and shares a cohort with, a prospective cohort study of ambient air pollutant effects on child development and respiratory health, being conducted by the Columbia Center for Children's Environmental Health (NIEHS R01 ES08977, P.I. Perera:11/01/03-10/31/08; 5 P01 ES09600/EPA RD-83214101, P.I. Perera, Co-I Rauh:11/01/03-10/31/08). Previous findings from the Children's Center study reveal adverse effects of prenatal exposure to CPF (validated with biomarkers in cord blood) on birth weight (Whyatt et al., 2004), cognitive and motor development, and neuro-behavioral problems at 3 years (Rauh et al., 2006). Affected neurobehavioral areas include attention and ADHD-- conditions with serious long-term clinical implications. Based on these findings, and evidence from the experimental literature showing long-term, possibly irreversible effects of CPF exposure on brain development and sensorimotor activity (Dam et al, 2000; Levin et al, 2002; Slotkin et al, 2005), we now propose to evaluate the longer-term neurodevelopmental effects of CPF in 300 9-year-old children. We will use Magnetic Resonance Imaging (MRI) to define the intermediary neurobiological effects of CPF exposure on the structure, metabolism, and anatomical connectivity of the brain in all 300 children. CPF was selected as a model for translational research because it is representative of the class of OP pesticides, well characterized, and well-studied in animals. Furthermore, agricultural and commercial uses continue, despite the 2001 residential ban by EPA. Specifically, we propose to: (1) assess the 9- year effects of prenatal and early childhood exposures to CPF on neurobehavioral (inattention, hyperactivity and depression) and neuropsychological functioning (attentional capacity, memory, impulse control and sensory motor functioning); and (2) assess the 9-year effects of prenatal and early childhood exposures to CPF on measures of brain structure (using anatomical MRI), brain chemistry/cellular metabolism (using magnetic resonance spectroscopy), and anatomical connectivity (using diffusion tensor imaging) in the same children. PUBLIC HEALTH RELEVANCE: This application is for a 5-year study to assess the effects of exposure to the organophosphorus pesticides, chlorpyrifos and diazinon, on neurobehavioral functioning in a cohort of inner-city children (n=400) who have reached 8-9 years of age. This work shares a cohort with a longitudinal study of ambient air pollutant effects on child development, from the prenatal period to 9 years of age, being conducted by the Columbia Center for Children's Environmental Health. The project has access to biomarkers of exposure, includes neuroimaging assessments on a subset of 60 children, and has potential for further informing regulatory safety standards for OP use in the United States.

描述（由申请人提供）：这项研究的目的是评估产前和产后暴露于有机磷（OP）农药毒性磷酸（CPF）对已经达到9岁的城市内部城市儿童中神经行为功能的影响。 This work builds on, and shares a cohort with, a prospective cohort study of ambient air pollutant effects on child development and respiratory health, being conducted by the Columbia Center for Children's Environmental Health (NIEHS R01 ES08977, P.I. Perera:11/01/03-10/31/08; 5 P01 ES09600/EPA RD-83214101, P.I. Perera，Co-I Rauh：11/01/03-10/31/08）。儿童中心研究的先前发现表明，在出生体重（Whyatt等，2004），认知和运动发育以及3年（Rauh等，2006）中，对CPF的暴露（用脐带血中的生物标志物证实）对出生体重（Whyatt等，2004），认知和运动发育以及神经行为问题的不利影响。受影响的神经行为区域包括注意力和多动症 - 具有严重长期临床意义的状况。基于这些发现以及实验文献的证据，表明CPF暴露对脑发育和感觉运动活性的长期，可能是不可逆的影响（Dam等，2000; Levin等，2002; Slotkin et al，2005），我们现在建议评估300岁9岁儿童CPF的长期神经发育影响。我们将使用磁共振成像（MRI）来定义CPF暴露对所有300名儿童中大脑的结构，代谢和解剖学连通性的中介神经生物学效应。 CPF被选为转化研究的模型，因为它代表了动物的特征性且经过充分研究的OP农药类别。此外，尽管EPA 2001年禁令，但农业和商业用途仍在继续。具体而言，我们建议：（1）评估CPF产前和幼儿期暴露于CPF对神经行为（不注意，多动症和抑郁症）以及神经心理学功能（注意力，记忆力，记忆力，冲动，冲动控制和感觉运动功能）的9年影响； （2）评估CPF产前和早期儿童期暴露于CPF对脑结构测量（使用解剖学MRI），脑化学/细胞代谢（使用磁共振光谱）和解剖学连接性（使用扩散张量成像）中的9年影响。公共卫生相关性：该应用程序是为期5年的研究，以评估暴露于有机磷的农药，毒灰里和二氮酮的影响，对已达到8-9岁的内城儿童（n = 400）中的神经行为功能（n = 400）。这项工作与哥伦比亚儿童环境健康中心进行了对环境空气污染对儿童发育的影响的纵向研究，对环境空气污染物对儿童发育的影响（从产前期到9岁）进行了纵向研究。该项目可以使用接触的生物标志物，包括60个儿童的神经影像学评估，并有可能进一步告知美国的监管安全标准以供美国使用。