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

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.

项目总结/文摘