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

应用新方法评估城乡饮用水，保护儿童健康

• 批准号: 10724209
• 负责人: Manuel Garcia-Jaramillo
• 金额: $ 18.09万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-02 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10724209
• 关键词: Adolescent; Adult; Affect; Area; Assessment tool; Behavioral; Biological Assay; Body Weight; Bottle feeding; Chemicals; Child; Child Health; Communities; Complex; Data; Detection; Diet; Disease; Elderly; Environmental Health; Epidemic; Exposure to; Farm; Fetal health; Foundations; Future; Goals; Health; Impairment; In Vitro; Infant; Infant Health; Intestines; Knowledge; Life; Link; Malignant Neoplasms; Mass Spectrum Analysis; Mediating; Mediation; Metabolism; Methods; Modeling; Monitor; Municipalities; National Institute of Environmental Health Sciences; Neurologic; Obesity; Oregon; Organ; Organic Chemicals; Outcome; Participant; Physiological; Poison; Population; Population Growth; Privatization; Production; Public Health; Regulation; Resolution; Retinal blind spot; Risk; Risk Assessment; Rural; Rural Community; Sampling; Services; Source; Strategic Planning; Surface; Testing; Time; Tissues; Toxic effect; Toxicity Tests; Toxicology; Translations; Variant; Water; Water Pollutants; Work; Zebrafish; biomarker discovery; climate change; contaminated drinking water; contaminated water; developmental disease; drinking water; gastrointestinal system; gut microbes; gut microbiota; host microbiota; human subject; improved; in silico; in vivo; innovation; member; mental function; metabolomics; microbiome; microbiome analysis; novel; novel strategies; open source; organic contaminant; pollutant; reproductive system disorder; response; safety assessment; socioeconomic development; water quality; water sampling; water testing; water treatment; web site; well water

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.

概括 我们生活在一个受污染的饮用水时代。饮用水重用，气候变化，人口增长和 密集农业是驱动这种污染的因素。同时喝水污染物已经 与癌症，肥胖，胃肠道系统失调等流行病有关，受损 心理功能以及其他发育和生殖疾病。饮用水中的有毒污染物是 对胎儿和婴儿健康特别有害。它们更容易受到有害污染物的影响，因为 他们的器官和组织仍在发展。先前的研究针对肠道微生物群作为活跃玩家 那个协会。但是，由于这些障碍的基础机制，由于 与鉴定微生物组介导的外部因素之间关系相关的挑战（即 饮食和污染物）和宿主代谢。由于有机微污染物数量大量，监测 仅使用靶向化学分析就不足以评估饮用水质量，仅涵盖一个很小的 化学物质的子集。最后，通常对当前饮用水污染物的健康风险进行评估 一次化学物质，这种方法错过了饮用水中同时发生污染物的健康影响 及其潜在的协同作用。我的中心假设是当前水龙头和井水质量 评估低估了我们暴露于饮用水中有机污染物及其对胎儿的影响 和婴儿健康。我的长期目标是（1）通过应用高度的高度评估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，特别是这些结果 与神经系统疾病有关。当前对与饮用水污染物相关的风险的了解 由于其检测，识别和测试相关的挑战，因此受到限制。因此，我的整体 此应用的目标是（1）应用高分辨率质谱（HRMS）和体外和 体内效应指导分析（EDA），以扩大当前水量监测策略的覆盖范围； （2）选择和 根据化学候选者的出现，丰度和毒性对化学候选者进行优先级； （3）评估关联 根据邮政编码和开源信息，在优先的污染物和水源中 公共卫生部网站上的俄勒冈州饮用水服务； （4）识别肠道代谢产物 变异解释了特定的肠道微生物与斑马鱼终点之间的关联。 （5）并提供 俄勒冈州农村和饮用水中发现的优先化学物质和混合物的全面清单。这项研究 将帮助EPA和DEQ的成员做出与进一步化学法规有关的更好的明智知识决定 在饮用水中。该应用程序响应了NIEHS战略计划2018 - 2023年的第一个主题，前进 环境健康科学（EHS），通过研究新兴关注的污染物混合物的影响， 预测毒理学和微生物组反应。