Characterization of Potential Harm Caused by Electronic Cigarette Flavor Chemicals and their Reaction Products

电子烟用香精化学品及其反应产物潜在危害的表征

基本信息

批准号：
10438598
负责人：
Prudence Talbot
金额：
$ 68.19万
依托单位：
UNIVERSITY OF CALIFORNIA RIVERSIDE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-20 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10438598
关键词：
3-Dimensional Abbreviations Adult Aerosols Affect Air Analytical Chemistry Biological Biological Assay California Cell Death Cell physiology Cells Chemicals DNA Data Databases Devices Disease Dose Electronic cigarette End Point Assay Environment Epithelial Cells Foundations Future Gases Gene Expression Glycerol Hand Health Heating Human Individual Inflammation Isopropanol Libraries Liquid Chromatography Liquid substance Lung Malignant Neoplasms Mass Fragmentography Mass Spectrum Analysis Mesenchyme Metabolism Methods Modeling Molecular Neoplasm Metastasis Nicotine Organ Oxidative Stress Pathway interactions Persons Poison Propylene Glycols Protocols documentation Reaction Reporting Research Risk Sampling Science Solvents System Testing Tissues Tobacco Toxic effect Toxicology United States National Institutes of Health Universities Work airway epithelium base cancer cell cell killing chemical reaction cinnamic aldehyde consumer product cytotoxic cytotoxicity e-cigarette aerosols electronic cigarette use electronic liquid epithelial to mesenchymal transition experimental study in vitro Assay interest liquid chromatography mass spectrometry oxidation response tobacco products toxicant transcriptome sequencing tumor progression vaping

项目摘要

Project Summary Electronic cigarettes (ECs) use heat to aerosolize “e-liquid” mixtures that usually contain high concentrations of flavor chemicals. This project will purchase 650 commercial e-liquids to: a) identify and quantify the flavor chemicals used plus their degradation reaction products (RxPs) formed upon vaping; and b) evaluate the cellular responses to those flavor chemicals often found at >1 mg/ml (viz. “dominant flavor chemicals”, DFCs), and to the aerosols produced on vaping. Tested will be 550 “popular” refill and cartomizer fluids and 100 fluids that have been anecdotally reported to cause sickness in users. Work will be conducted at two campuses: Portland State University for analytical chemistry, and University of California Riverside for human toxicology. Aim 1 (PSU). DFCs and vaping RxPs will be identified and quantified for the 650 fluids. Aerosols made using a range of devices at varied power will be collected in isopropanol and analyzed using gas chromatography/ mass spectrometry (GC/MS) and liquid chromatography/MS/MS. Identification will proceed with standards. RxPs formed from flavor chemicals will be unambiguously distinguished from RxPs from the EC solvents. Aim 2 (UCR). Vape aerosols made using lab-prepared fluids containing the identified DFCs will be made with a range of devices, and screened for cytotoxicity in dose-response experiments using in vitro assays in conjunction with BEAS-2B lung epithelial cells from normal human adults. The aerosols that are most cytotoxic will be studied in depth using an air-liquid interface exposure system with the 3D EpiAirway platform that recapitulates human respiratory epithelium. Individual DFCs will be tested using six cancer-related mode-of- action assays including assays for an epithelial to mesenchymal transition (EMT) that we have observed with some EC products. Alterations in gene expression will be determined using RNA-seq and affected pathways identified. Mixtures of DFCs will be tested at the same relative proportions found in consumer products. Aim 3 (UCR). Since Aim 2 will examine heat generated aerosols, both DFCs and their RxPs products will have been present. Aim 3 will differentiate the DFCs and RxP toxicities by exposing the 3D EpiAirway platform to aerosols generated without heat and containing individual DFCs or the identified RxPs from heating. Endpoint assays will proceed as in Aim 2 to isolate toxicity to individual chemicals. Summary. Little is known about the health effects of flavor chemicals used in ECs. This project will fill an important informational gap with comprehensive new data. Specific toxicants will be identified and the effects of mixing DFCs will be evaluated. Results will be posted on an online database that will be accessible to any interested persons or organization, and will provide foundational information for future understanding of flavor chemicals in tobacco products. The data, the first of their kind, will contribute to a foundation of science upon which the NIH can develop future research directions to protect consumers’ health and protect those exposed by second- and thirdhand means.

项目概要电子烟 (EC) 利用热量雾化通常含有高浓度物质的“电子烟液”混合物该项目将购买 650 种商业电子液体，以： a) 识别和量化风味。 b) 评估所使用的化学品及其在吸食电子烟时形成的降解反应产物 (RxP)；细胞对这些风味化学物质的反应通常 >1 mg/ml（即“主要风味化学物质”，DFC），测试的将是 550 种“流行”补充液和雾化器液体以及 100 种液体。据传闻会导致用户生病的工作将在两个校区进行：波特兰州立大学分析化学专业和加州大学河滨分校人类毒理学专业。目标 1 (PSU) 将识别和量化使用 650 种气雾剂制造的 DFC 和电子烟 RxP。一系列不同功率的设备将被收集在异丙醇中并使用气相色谱法进行分析/ 质谱 (GC/MS) 和液相色谱/MS/MS 将按照标准进行鉴定。由香料化学品形成的 RxP 将与 EC 溶剂形成的 RxP 明确区分开。目标 2 (UCR)。使用实验室制备的含有已识别 DFC 的液体制成的电子烟气雾剂将采用以下材料制成。一系列设备，并使用体外测定在剂量反应实验中筛选细胞毒性与正常成人的 BEAS-2B 肺上皮细胞结合最具细胞毒性的气溶胶。将使用带有 3D EpiAirway 平台的气液界面曝光系统进行深入研究概括人类呼吸道上皮细胞将使用六种癌症相关模式进行测试。作用测定，包括我们观察到的上皮间质转化（EMT）测定一些 EC 产品将使用 RNA-seq 和受影响的途径来确定基因表达的改变。确定的 DFC 混合物将以与消费品中相同的相对比例进行测试。目标 3 (UCR) 由于目标 2 将检查产生热量的气溶胶，因此 DFC 及其 RxPs 产品都将具有 Aim 3 将通过将 3D EpiAirway 平台暴露于环境来区分 DFC 和 RxP 毒性。不加热产生的气溶胶，含有单独的 DFC 或通过加热确定的 RxP。测定将按照目标 2 进行，以隔离单个化学品的毒性。摘要：对于 EC 中使用的香料化学品对健康的影响知之甚少，该项目将填补这一空白。将确定与全面的新数据的重要信息差距及其影响。混合 DFC 的结果将发布在任何人都可以访问的在线数据库上。感兴趣的个人或组织，并将为将来了解风味提供基础信息这些数据是此类数据中的第一个，将有助于奠定科学基础。 NIH 可以制定未来的研究方向，以保护消费者的健康和接触者通过二手和三手手段。