Evaluation of novel markers of exposure and biological response to 1,4-dioxane

1,4-二恶烷暴露和生物反应的新型标记物的评估

• 批准号: 10698011
• 负责人: Nicole Deziel
• 金额: $ 28.86万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-07 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10698011
• 关键词: Address; Adult; Affect; Animal Experiments; Area; Awareness; Biological; Biological Assay; Biological Markers; Biological Monitoring; Blood; Blood specimen; Carcinogens; Chemicals; Classification; Clinical; Communication; Communities; County; Cross-Sectional Studies; Data; Data Analyses; Dioxanes; Disease; Environment; Ethylene Dichlorides; Evaluation; Exposure to; Fright; Goals; Guidelines; Hazardous Substances; Health; Hepatocarcinogenesis; Hepatotoxicity; High Prevalence; Home; Human; Individual; Industrialization; Link; Lipids; Literature; Liver; Long Island; Mass Spectrum Analysis; Measures; Municipalities; New York; North Carolina; Participant; Policy Maker; Population; Probability; Questionnaires; Research; Research Personnel; Risk; Sampling; Serum; Site; Solvents; Source; Superfund; Surface; System; Techniques; Test Result; Time; Translational Research; Trichloroethanes; Trichloroethylene; United States; United States Environmental Protection Agency; Variant; Water; Water Pollutants; Water Supply; biomarker validation; cancer risk; candidate selection; cohort; community engagement; contaminated drinking water; data management; drinking water; exposed human population; ground water; health data; insight; metabolome; metabolomics; new technology; novel marker; novel strategies; personal care products; pollutant; programs; public drinking; remediation; response; sensor; superfund site; tool; volatile organic compound; water sampling; water sampling/testing; water testing

Project Summary/Abstract 1,4-Dioxane (1,4-DX) is a synthetic chemical historically used as a stabilizer of chlorinated solvents and currently used in a range of consumer and personal care products. Over one-fifth of the US public drinking water supply contains detectable levels of 1,4-DX, and approximately 7% of drinking water samples tested exceed the federal cancer risk level of 0.35 μg/L. Widespread contamination of drinking water has been observed in groundwater in Nassau and Suffolk Counties of Long Island, New York, where 75% of population have water sources with 1,4-DX concentrations exceeding 0.35 μg/L. Furthermore, standard municipal treatment systems are ineffective at removing 1,4-DX, enabling its persistence in drinking water supplies. The US Environmental Protection Agency (EPA) has designated 1,4-DX as a “high priority” chemical and classified it as a probable human carcinogen based on evidence from experimental animal studies, primarily based on effects on the liver. Despite the high prevalence in the environment and potential human health risks, there is a paucity of human exposure and health data. We will apply novel approaches to evaluate exposure to 1,4-DX and co-occurring contaminants (such as the volatile organic compounds 1,1-dichloroethane (DCA), trichloroethylene (TCE), and 1,1,1-trichloroethane (TCA)) in two communities: Long Island, New York (our primary study area) and Cape Fear River Watershed, North Carolina (secondary study area). We will use our newly developed, highly sensitive mass spectrometry-based assay for assessment of exposure to 1,4-DX in water and blood samples. In addition, we will evaluate associations between exposure to 1,4-DX and co- contaminants and levels of endogenous metabolites and lipids in blood using both untargeted and targeted metabolomics. The use of biomonitoring and metabolomics provide powerful tools to assess early exposures and biological changes in the years preceding clinical manifestation of disease. We propose a cross-sectional study on Long Island (an area with many Superfund sites potentially contributing to contamination of drinking water with 1,4-DX) to i) assess human exposure to 1,4-DX and evaluate the relationship between environmental and biological exposure indicators, ii) evaluate temporal variability of exposure to 1,4-DX and metabolite levels by comparing data from two different US regions with different water sources (ground water in NY and surface water in NC), and iii) evaluate the relationship between 1,4-DX exposure and metabolites of biological responses particularly for liver toxicity and carcinogenesis. This project will greatly enhance our understanding of the extent of exposure to 1,4-DX (and its co-occurring contaminants) in drinking water and the potential for human health effects. The results will provide scientific evidence for policy makers to set guidelines for concentration standards for 1,4-DX and provide researchers in the Superfund Research Program with new tools to detect hazardous substances in the environment as well as novel technologies for remediation.

项目概要/摘要 1,4-二恶烷 (1,4-DX) 是一种合成化学品，历史上用作氯化溶剂和 目前用于一系列消费品和个人护理产品。超过五分之一的美国公众饮酒 供水中含有可检测水平的 1,4-DX，约 7% 的饮用水样本经过检测 超过联邦癌症风险水平 0.35 μg/L。饮用水普遍受到污染 在纽约长岛拿骚县和萨福克县的地下水中观察到，那里 75% 的人口 水源中 1,4-DX 浓度超过 0.35 μg/L。此外，标准市政 处理系统无法有效去除 1,4-DX，使其在饮用水供应中持续存在。这 美国环境保护署 (EPA) 已将 1,4-DX 指定为“高度优先”化学品并分类 根据实验动物研究的证据，主要基于 对肝脏的影响。尽管在环境中的患病率很高并且存在潜在的人类健康风险，但仍然存在 缺乏人类暴露和健康数据。我们将采用新方法来评估 1,4-DX 暴露情况 和共存污染物（例如挥发性有机化合物 1,1-二氯乙烷 (DCA)、 三氯乙烯 (TCE) 和 1,1,1-三氯乙烷 (TCA)）在两个社区：纽约长岛（我们的 主要研究区）和北卡罗来纳州开普菲尔河流域（次要研究区）。我们将使用我们的 新开发的高灵敏度质谱分析法，用于评估 1,4-DX 的暴露情况 水和血液样本。此外，我们将评估暴露于 1,4-DX 和协同作用之间的关联。 使用非靶向和靶向方法检测血液中内源代谢物和脂质的污染物和水平 代谢组学。生物监测和代谢组学的使用为评估早期暴露提供了强大的工具 以及疾病临床表现前几年的生物学变化。我们提出了一个横截面 长岛研究（该地区有许多超级基金站点，可能导致饮用水污染） 含有 1,4-DX 的水) i) 评估人体对 1,4-DX 的暴露并评估两者之间的关系 环境和生物暴露指标，ii) 评估 1,4-DX 暴露的时间变异性和 通过比较美国两个不同地区不同水源（地下水）的数据来确定代谢水平 纽约州和北卡罗来纳州地表水)，以及 iii) 评估 1,4-DX 暴露与代谢物之间的关系 生物反应，特别是肝毒性和致癌作用。该项目将大大增强我们的 了解饮用水中 1,4-DX（及其共存污染物）的暴露程度 对人类健康的潜在影响。研究结果将为政策制定者制定政策提供科学依据 1,4-DX 浓度标准指南并为超级基金研究计划的研究人员提供 拥有检测环境中有害物质的新工具以及检测环境中有害物质的新技术 补救措施。