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: 10361887
• 负责人: Nicole Deziel
• 金额: $ 40.14万
• 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/10361887
• 关键词: Address; Adult; Affect; Animals; Area; Awareness; Biological; Biological Assay; Biological Markers; Biological Monitoring; Blood; Blood specimen; Carcinogens; Chemicals; 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; Questionnaires; Research; Research Personnel; Risk; Rivers; 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; base; 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; Address; Adult; Affect; Animals; Area; Awareness; Biological; Biological Assay; Biological Markers; Biological Monitoring; Blood; Blood specimen; Carcinogens; Chemicals; 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; Questionnaires; Research; Research Personnel; Risk; Rivers; 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; base; 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.

项目摘要/摘要 1,4-二氧烷（1,4-DX）是一种合成化学物质，历史上用作氯化溶液的稳定剂和 目前用于各种消费者和个人护理产品。美国公共饮酒的五分之一超过五分之一 供水含有1,4-DX的可检测水平，大约7％的饮用水样品测试了 超过0.35μg/L的联邦癌症风险水平。饮用水的宽度污染 在拿骚和纽约长岛的萨福克县的地下水中观察到，那里有75％的人口 具有1,4-DX浓度超过0.35μg/L的水源。此外，标准市政 治疗系统无效地去除1,4-DX，使其在饮用水供应方面的持久性。 美国环境保护局（EPA）将1,4-DX指定为“高优先级”化学物质，并被分类 基于实验动物研究的证据，它是有问题的人类致癌物，主要基于 对肝脏的影响。尽管环境中的患病率很高，而且潜在的人类健康风险，但仍有一个 人类暴露和健康数据的稀少。我们将采用新颖的方法来评估对1,4-DX的接触 和共发生的污染物（例如挥发性有机化合物1,1-二氯乙烷（DCA）， 在两个社区中的三氯乙烯（TCE）和1,1,1-三氯乙烷（TCA））：纽约长岛（我们的长岛） 初级研究区域）和北卡罗来纳州的Cape Fear River流域（二级研究区）。我们将使用我们的 新开发的，高度敏感的质谱评估评估，用于评估1,4-DX的暴露 水和血液样本。此外，我们将评估暴露于1,4-DX和共同的关联 使用未靶向和靶向的血液中内源性代谢物和脂质的污染物和脂质水平 代谢组学。生物监测和代谢组学的使用提供了有力的工具来评估早期暴露 以及在疾病临床表现之前的几年中的生物学变化。我们提出了一个横截面 在长岛（Long Island i）评估人类对1,4-DX的接触并评估 环境和生物暴露指标，ii）评估暴露于1,4-DX和 代谢物水平通过比较来自两个不同地区的数据与不同的水源（地下水） 在纽约州和北卡罗来纳州的地表水中，iii）评估1,4-DX暴露与代谢物之间的关系 生物学反应尤其对肝脏毒性和致癌作用。这个项目将大大增强我们的 了解暴露于饮用水中的1,4-DX（及其同时发生污染物）的暴露程度 结果将为决策者提供科学证据 1,4-DX的集中标准指南，并为超级基金研究计划提供研究人员 借助发现环境中有害物质的新工具以及新的技术 修复。