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: 9157911
• 负责人: Tracey J. Woodruff
• 金额: $ 59.16万
• 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/9157911
• 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; Generations; Health; Hispanics; Human; Income; Infant; Liquid Chromatography; Longevity; Malignant Neoplasms; Mass Spectrum Analysis; Maternal Exposure; Measures; 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; abstracting; 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; 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.

项目概要/摘要 事实证明，在子宫内接触多种环境化学物质会对整个健康产生不利影响 寿命缩短，导致不良出生结果、神经发育缺陷、糖尿病和肥胖，以及 癌症。然而，限制我们描述和解决发育健康风险能力的一个关键数据差距是 缺乏关于新生儿接触各种工业化学品的程度的数据 我们。在美国大量生产和使用的化学品中，90% 以上（>25,000 磅/年）是 未在大规模人体生物监测研究中进行测量。此外，目前的生物监测方法 需要预先选择化合物来开发和验证目标分析方法；缺乏 工业或商业产品中化学品使用数据的缺乏阻碍了准确预测化学品使用情况的能力 在近 8000 种高使用化学品中，美国人最有可能接触到。为了应对这些挑战， 我们的项目将利用液相色谱法推进一个创新的、以发现为导向的研究项目—— 四极杆飞行时间质谱 (LC-QTOF/MS) 对以下物质进行一般怀疑筛查 人口统计中大约 700 种环境有机酸 (EOA) 的存在和共存 母婴对的不同群体。我们还将演示该屏幕如何告知 选择化学品用于有针对性的分析方法开发，同时解决人口差异 EOA 暴露以及母体血清水平准确反映子宫暴露的程度。我们专注 在 EOA 上，因为它们更容易被我们的 LC-QTOF/MS 检测到，因此是我们小说的一个很好的模型 方法。此外，它们在结构上与已知会对发育产生不利影响的化学物质相似，因此 的潜在健康风险。使用 LC-QTOF/MS，我们将筛选 300 份匹配的脐带和母体血清 从种族和经济多样化的人群中收集样本，约 700 个 EOA。使用 LC- 根据 QTOF/MS 结果，我们将确定 10 种可能广泛人类接触的 EOA 人口和孕产妇-新生儿暴露差异。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 西班牙裔与非西班牙裔白人、美国裔与外国出生者以及低裔美国人中 10 种 EOA 的脐带血清水平 与高收入亚组相比，并评估母婴对之间暴露的差异。我们的 发现驱动的可疑筛查将开创一种生物监测方法，优先考虑目标化学品 方法开发基于其在人群中检测到的可能性。这也将是一个 对于其他研究人员来说，这是宝贵的资源，他们可以在产前查询新化学物质的暴露情况 时期。最后，我们还将为目标方法清单做出实质性贡献 环境化学品并生成有关脆弱和易感人群的重要新暴露数据 这是确定有害化学品健康风险特征并为预防提供信息的基础。