Discovery of novel environmental chemicals in a diverse population of maternal-infant pairs

在不同母婴群体中发现新型环境化学物质

• 批准号: 9355643
• 负责人: Tracey J. Woodruff
• 金额: $ 57.64万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9355643
• 关键词: Address; Adult; Analytical Chemistry; Biological; Biological Monitoring; Birth; Chemical Exposure; Chemicals; Childhood; Commerce; Complement; Data; Detection; Development; Diabetes Mellitus; Equipment and supply inventories; Ethnic Origin; Evaluation; Exposure to; Foundations; Generations; Health; Hispanics; Human; Income; Industrialization; Infant; Liquid Chromatography; Longevity; Malignant Neoplasms; Mass Spectrum Analysis; Maternal Exposure; Methods; Modeling; Mothers; National Health and Nutrition Examination Survey; Neurodevelopmental Deficit; Newborn Infant; Not Hispanic or Latino; Obesity; Outcome; Performance; Perinatal Exposure; Poison; Population; Population Heterogeneity; Prevention; Production; Proxy; Race; Research; Research Personnel; Research Project Grants; Research Proposals; Resolution; Resources; Risk; Risk Assessment; Sampling; Scientific Advances and Accomplishments; Screening Result; Serum; Socioeconomic Status; Specimen; Subgroup; Time; Toxic effect; Umbilical cord structure; Variant; adverse outcome; analytical method; base; environmental chemical; exposed human population; fetal; fetus at risk; improved; innovation; maternal serum; method development; neonatal exposure; neonate; novel; novel strategies; organic acid; prenatal; prenatal exposure; racial and ethnic disparities; socioeconomic disparity; tandem mass spectrometry

Project Summary/Abstract In utero exposure to multiple environmental chemicals has been shown to adversely impact health throughout the lifespan, leading to adverse birth outcomes, neurodevelopmental deficits, diabetes and obesity, and cancer. Yet, a key data gap limiting our ability to characterize and address developmental health risks is the lack of data on the extent to which neonates are exposed to the vast array of industrial chemicals used in the US. Over 90% of the chemicals manufactured and used in high volumes (>25,000 pounds/year) in the US are not measured in large-scale human biomonitoring studies. Further, the current biomonitoring approach requires a priori selection of compounds for which to develop and validate targeted analytical methods; the lack of data on chemical use in industrial or commercial products hinders the ability to accurately anticipate to which of the almost 8000 high use chemicals the US population is most likely exposed. To address these challenges, our project will advance an innovative, discovery-driven research project using liquid chromatography- quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) to perform a General Suspects Screen for the presence and co-occurrence of approximately 700 Environmental Organic Acids (EOAs) in a demographically diverse population of maternal-neonate pairs. We will also demonstrate how this screen can inform the selection of chemicals for targeted analysis methods development while addressing demographic disparities in EOA exposure and the extent to which maternal serum levels accurately reflect in utero exposures. We focus on EOAs because they are more easily detected by our LC-QTOF/MS and thus are a good model for our novel approach. Also, they are structurally similar to chemicals known to adversely impact development and thus are of potential health risk. Using LC-QTOF/MS, we will screen 300 matched umbilical cord and maternal serum samples, collected from a racially and economically diverse population, for ~ 700 EOAs. Using the LC- QTOF/MS results, we will identify 10 EOAs with potential for widespread human exposure and for demographic and maternal-neonatal exposure disparities. We will develop LC-MS/MS methods to confirm and quantify these 10 EOAs, and evaluate the performance of the LC-QTOF/MS screen. We will compare umbilical cord serum levels of the 10 EOAs in Hispanic versus non-Hispanic white, US– versus foreign-born, and low– versus high-income subgroups, and assess differences in exposures between maternal-fetal pairs. Our discovery-driven, suspect screen will pioneer a biomonitoring approach that prioritizes chemicals for targeted method development based on their likelihood of detection in the human population. It will also be an invaluable resource for other researchers who may query it for novel chemical exposures during the prenatal period. Finally, we will also make substantial contributions to the inventory of targeted methods for environmental chemicals and generate critical new exposure data on vulnerable and susceptible populations that is foundational to characterize and inform prevention of health risks from harmful chemicals.

项目摘要/摘要 在子宫内暴露于多种环境化学物质中，已证明对整个健康产生不利影响 寿命，导致不良出生结果，神经发育缺陷，糖尿病和肥胖，以及 癌症。但是，一个关键数据差距限制了我们表征和解决发展健康风险的能力的是 缺乏有关新生儿在多大程度上暴露于使用的大量工业化学品的程度的数据 我们。在美国，超过90％的化学物质以高量（> 25,000磅）制造和使用 在大规模的人类生物监测研究中未测量。此外，当前的生物监测方法 需要先验选择用于开发和验证靶向分析方法的化合物；缺乏 工业或商业产品中化学使用的数据妨碍准确预期的能力 在近8000种高使用化学物质中，美国人口很可能暴露出来。为了应对这些挑战， 我们的项目将使用液相色谱法推进创新的，发现驱动的研究项目 - 四杆飞机质谱（LC-QTOF/MS）执行一般嫌疑人屏幕 在人口统计学中，大约700个环境有机酸（EOA）的存在和同时存在 孕产妇神经对的潜水员人群。我们还将演示该屏幕如何通知 选择针对性分析方法开发的化学品，同时解决人口统计分布 EOA暴露以及材料血清在多大程度上准确反映子宫内暴露的程度。我们集中精力 在EOA上，因为我们的LC-QTOF/MS更容易检测它们，因此是我们小说的好模型 方法。此外，它们在结构上与已知的化学物质相似，从而对发展产生不利影响，因此 潜在的健康风险。使用LC-QTOF/MS，我们将筛选300个匹配的脐带和母体系列 从大约700个EOA中收集的样品，从大致和经济上的人群中收集。使用LC- QTOF/MS结果，我们将识别10个具有宽度人类暴露的EOA和 人口统计学和孕产妇暴露分布。我们将开发LC-MS/MS方法来确认和 量化这10个EOA，并评估LC-QTOF/MS屏幕的性能。我们将比较脐带 西班牙裔与非西班牙裔白色的10个EOA的脐带血清水平，美国与外国出生，低 - 与高收入亚组相比，以及在托尔特尔对之间暴露的评估差异。我们的 发现驱动的可疑屏幕将先驱一种生物监测方法，该方法优先考虑针对目标的化学品 方法开发基于他们在人口中检测的可能性。这也将是 对于其他可能在产前期间对新型化学暴露的研究人员来说，其他研究人员的宝贵资源 时期。最后，我们还将为目标方法的清单做出重大贡献 环境化学品并生成有关脆弱和易感人群的关键新曝光数据 这是表征和告知预防有害化学物质健康风险的基础。