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

项目总结/摘要 在子宫内暴露于多种环境化学品已被证明对整个健康产生不利影响 寿命，导致不良的出生结果，神经发育缺陷，糖尿病和肥胖症， 癌然而，一个关键的数据差距限制了我们描述和解决发育健康风险的能力， 缺乏关于新生儿在多大程度上暴露于工业生产中使用的大量工业化学品的数据， 我们在美国，超过90%的化学品生产和大量使用（> 25，000磅/年）， 在大规模人体生物监测研究中没有测量到。此外，目前的生物监测方法 需要事先选择化合物，以开发和验证有针对性的分析方法;缺乏 关于工业或商业产品中化学品使用的数据的缺乏阻碍了准确预测 在美国人口最有可能接触的近8000种高使用化学品中。为了应付这些挑战， 我们的项目将推进一个创新的，发现驱动的研究项目，使用液相色谱- 四极杆飞行时间质谱法（LC-QTOF/MS）进行一般可疑筛查， 在人口统计学上，大约700种环境有机酸（EOA）的存在和共存 母亲和新生儿对的多样性。我们还将演示此屏幕如何通知 选择化学品以制定有针对性的分析方法，同时解决 EOA暴露和母体血清水平准确反映子宫内暴露的程度。我们专注 因为它们更容易被我们的LC-QTOF/MS检测到，因此是我们的新的 approach.此外，它们在结构上类似于已知会对发展产生不利影响的化学品，因此， 潜在的健康风险。采用LC-QTOF/MS对300份脐带血和母血进行筛查 样本，从种族和经济多样化的人群中收集，约700个EOA。使用LC- 根据QTOF/MS结果，我们将确定10个可能广泛暴露于人体的EOA， 人口统计学和母婴接触差异。我们将开发LC-MS/MS方法来确认和 量化这10个EOA，并评价LC-QTOF/MS筛选的性能。我们将比较脐带 西班牙裔与非西班牙裔白色人、美国出生与外国出生的人以及低 与高收入亚组相比，并评估母体-胎儿对之间的暴露差异。我们 以发现为导向的可疑筛选将开创一种生物监测方法， 方法开发基于其在人群中检测的可能性。这也将是一 对于其他研究人员来说，这是一个宝贵的资源，他们可能会在产前询问新的化学暴露 期最后，我们还将对有针对性的方法清单作出实质性贡献， 环境化学品，并生成关于脆弱和易受影响人群的新的重要接触数据 这是确定有害化学品健康风险的特征和为预防有害化学品健康风险提供信息的基础。

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.