Protecting children's health by applying novel approaches to assess urban and rural drinking water

总结 我们生活在一个饮用水污染的时代。饮用水再利用、气候变化、人口增长以及 集约化农业是造成这种污染的因素。同时饮用水污染物已被 与流行性疾病如癌症、肥胖、胃肠系统失调、 精神功能，以及其他发育和生殖疾病。饮用水中的有毒污染物是 对胎儿和婴儿的健康尤其有害。它们更容易受到有害污染物的影响， 他们的器官和组织还在发育以前的研究将肠道微生物群作为一个积极的参与者 这个协会。然而，这些损伤的潜在机制仍然不清楚， 与鉴定微生物组介导的外部因素之间的关系相关的挑战（即， 饮食和污染物）和宿主代谢。由于大量的有机微污染物，监测 仅仅使用有针对性的化学分析不足以评估饮用水质量， 化学品的一部分。最后，目前的饮用水污染物的健康风险通常是评估一个 化学品，这种方法忽略了饮用水中共存污染物对健康的影响 及其潜在的协同效应。我的主要假设是，目前的自来水和井水质量 评估低估了我们对饮用水中有机污染物的暴露及其对胎儿的影响 和婴儿健康。我的长期目标是：（1）通过应用高质量的技术来改善饮用水质量评估， 污染物混合物的吞吐量识别和优先级策略，以及（2）阐明因果关系 饮用水污染物与儿童负面健康结果之间的关系，特别是那些 与神经系统疾病有关。目前对饮用水污染物相关风险的认识 由于与它们的检测、识别和测试相关联的挑战，因此，我的总体 本申请的目的是（1）应用高分辨率质谱（HRMS），并在体外和体内 体内效应导向分析（EDA），以扩大当前水监测策略的覆盖范围;（2）选择和 根据化学物质的出现、丰度和毒性对候选化学物质进行优先排序;（3）评估关联性 根据邮政编码和开源信息， 公共卫生部网站上的俄勒冈州饮用水服务;（4）确定肠道代谢物， 变异解释了特定肠道微生物与斑马鱼终点之间的关联;（5）并提供了一个 在俄勒冈州农村和饮用水中发现的优先化学品和混合物的综合清单。本研究 将帮助EPA和DEQ的成员在进一步的化学品法规方面做出更明智的决定 在饮用水中。该应用程序响应了NIEHS战略计划2018-2023的第一个主题， 环境健康科学（EHS），通过研究新出现的污染物混合物的影响， 预测毒理学和微生物组反应。

SUMMARY We live in an era of contaminated drinking water. Potable water reuse, climate change, population growth, and intensive farming are factors that drive this contamination. Concurrently drinking water contaminants have been linked with epidemic diseases such as cancer, obesity, dysregulation of the gastrointestinal systems, impaired mental functions, and other developmental and reproductive diseases. Toxic pollutants in drinking water are particularly hazardous for fetal and infant health. They are more vulnerable to harmful contaminants because their organs and tissues are still developing. Previous studies have targeted gut microbiota as an active player of that association. However, the mechanisms underlying these impairments remain poorly defined due to challenges associated to the identification of microbiome-mediated relationships between external factors (i.e., diet and contaminants) and host metabolism. Due to the massive number of organic micropollutants, monitoring using targeted chemical analyses alone is insufficient to assess drinking water quality, covering only a very small subset of the chemicals. Finally, current health risks of drinking water contaminants are typically assessed one chemical at a time, an approach that misses the health impacts of co-occurring contaminants in drinking water and their potential synergistic effects. My central hypothesis is that current tap and well water quality assessments underestimate our exposure to organic contaminants in drinking water and their impact on fetal and infant health. My long-term goals are to (1) improve drinking water quality assessments, by applying high- throughput identification and prioritization strategies of contaminant mixtures, as well as (2) elucidate causal relationships between drinking water contaminants and negative health outcomes in children, specifically those related to neurological conditions. Current knowledge of the risks associated with drinking water contaminants is limited due to the challenges associated with their detection, identification, and testing. Therefore, my overall objectives for this application are to (1) apply high-resolution mass spectrometry (HRMS) and in vitro and in vivo effect-directed analysis (EDA) to expand the coverage of current water monitoring strategies; (2) select and prioritize chemical candidates based on their occurrence, abundance, and toxicity; (3) evaluate associations among prioritized contaminants and water sources according to zip code and open source information found in the Oregon Drinking Water Services at the Public Health Division Website; (4) identify gut metabolites whose variation explains the association between specific gut microbes and zebrafish endpoints; (5) and provide a comprehensive list of prioritized chemicals and mixtures found in rural and drinking water in Oregon. This study will help members from the EPA and DEQ make better informed decisions related to further chemical regulations in drinking water. This application responds to the first theme of the NIEHS strategic plan 2018-2023, Advancing Environmental Health Sciences (EHS), by studying the effects of contaminant mixtures of emerging concern, predictive toxicology, and microbiome responses.