Novel Biomarker to Identify Critical Windows of Susceptibility to Metal Mixture

用于识别金属混合物敏感性关键窗口的新型生物标记物

• 批准号: 9127482
• 负责人: Manish Arora
• 金额: $ 70.83万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9127482
• 关键词: 8 year old; Address; Affect; Arsenic; Biological Markers; Birth; Cadmium; Chemical Exposure; Chemicals; Child; Childhood; Cohort Studies; Complex; Data; Data Analyses; Data Set; Dental; Dentin; Development; Dose; Educational workshop; Environment; Environmental Health; Exposure to; Funding; Future; Goals; Health; Institutes; Lead; Life; Machine Learning; Manganese; Metal exposure; Metals; Methodology; Methods; Mexico; Modeling; National Institute of Environmental Health Sciences; Neuraxis; Neurodevelopmental Deficit; Nutrient; Organic Chemicals; Outcome; Perinatal; Phenotype; Predisposition; Process; Public Health; Publishing; Recording of previous events; Research; Research Design; Risk Factors; Sample Size; Sampling; Science of genetics; Second Pregnancy Trimester; Social Sciences; Staging; Statistical Methods; Sum; Techniques; Testing; Third Pregnancy Trimester; Time; Tooth structure; Toxicant exposure; Toxicogenetics; Weight; Work; Zinc; cognitive function; cohort; cost; deciduous tooth; developmental neurotoxicity; early childhood; early life exposure; experience; knowledge base; learning strategy; neurodevelopment; neurotoxic; neurotoxicology; novel; novel marker; programs; prospective; public health relevance; response; tool; toxicant

 DESCRIPTION (provided by applicant): Neurodevelopment and cognitive function are among the most important outcomes in public health, particularly with the rise of knowledge-based economies. While it is widely believed that the simultaneous presence of several toxic exposures can alter developmental trajectories of the central nervous system, studies designed to address mixed chemical exposures are rare, and represent a critical need in the field of public health. Multiple barriers are inherent to conducting mixtures research and must be overcome if this field is to progress. Obvious barriers include the need for large sample sizes and prospective data to assess exposure timing (i.e. critical developmental windows). Two additional barriers include exposure misclassification and lack of statistical approaches available for higher dimensional interactions. Our proposal addresses all of these barriers directly and will establish a framework for the study of chemical mixtures that can be applied broadly in environmental health. We have developed a novel biomarker that can objectively reconstruct the dose and timing of past chemical exposure using deciduous teeth. This biomarker differs from standard tooth biomarkers as it combines sophisticated histological and chemical analyses to precisely sample dentine layers corresponding to specific life stages, generating integrated, longitudinal weekly exposure estimates in the second and third trimesters and during early childhood. Our proposal will address mixed metal exposure, as a first step. We note, however, that our approach can and will be applied to organic chemicals in the future, and we are in parallel developing methods for their analysis in teeth. On another front, we will also apply cutting-edge statistical machine learning methods. In this study, we will focus on five metals/metalloids that are of public health significance, manganese (Mn), lead (Pb), arsenic (As), zinc (Zn) and cadmium (Cd). We will conduct this study in the Early Life Exposures in MExico and NeuroToxicology (ELEMENT), a prospective birth cohort using advanced methods in social science, genetics and toxicology to assess transdisciplinary risk factors impacting neurodevelopment.

 描述（由适用提供）：神经发育和认知功能是公共卫生中最重要的结果之一，尤其是随着知识经济的兴起。尽管人们普遍认为，几种有毒暴露的简单存在可以改变中枢神经系统的发育轨迹，但旨在解决混合化学暴露的研究很少见，并且在公共卫生领域代表了迫切需要。多个障碍是进行混合研究的继承，并且必须克服该领域的进展。明显的障碍包括需要大型样本量和预期数据来评估曝光时间（即关键的发育窗口）。额外的两个障碍包括曝光错误分类和缺乏可用于更高的统计方法 维度相互作用。我们的建议直接解决了所有这些障碍，并将建立一个可以在环境健康中广泛应用的化学混合物的框架。我们已经开发了一种新型的生物标志物，可以客观地重建使用决定牙齿的过去化学暴露的剂量和时机。该生物标志物与标准牙齿生物标志物不同，因为它结合了与特定生命阶段相对应的精确样品牙本质层，在第二和第三个三个孕期以及童年期间产生了综合的，纵向的每周暴露估计。第一步，我们的建议将解决混合金属暴露。但是，我们注意到，将来我们的方法可以而且将适用于有机化学物质，并且我们正在同时开发其在牙齿中分析的方法。在另一个方面，我们还将采用尖端的统计机器学习方法。在这项研究中，我们将重点关注五种具有公共卫生意义的金属/金属，锰（MN），铅（PB），砷（AS），锌（Zn）和镉（CD）。我们将在墨西哥的早期暴露和神经毒理学（Element）中进行这项研究，这是一种使用社会科学，遗传学和毒理学中先进方法的前瞻性出生队列，以评估影响神经发育的跨学科风险因素。