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

• 批准号: 10215535
• 负责人: Prudence Talbot
• 金额: $ 68.32万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-20 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10215535
• 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; Structure of respiratory epithelium; System; Testing; Tissues; Tobacco; Toxic effect; Toxicology; United States National Institutes of Health; Universities; Work; 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

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.

项目摘要 电子香烟（EC）使用热量来雾化通常含有高浓度的尼古丁的“电子液体”混合物。 香料化学品该项目将购买650个商业电子液体，以：a）识别和量化味道 使用的化学品及其在吸电子烟时形成的降解反应产物（RxP）;以及B）评估 细胞对那些经常在>1 mg/ml发现的风味化学物质（即“主要风味化学物质”，DFC）的反应， 以及电子烟产生的气溶胶。测试将是550“流行”的笔芯和雾化器流体和100流体 有传闻称会导致使用者生病。工作将在两个校区进行： 波特兰州立大学的分析化学和加州大学滨江的人类毒理学。 目标1（PSU）。将对650种液体的DFC和电子烟RxP进行识别和定量。气雾剂是用 将在异丙醇中收集不同功率下的一系列器械，并使用气相色谱法进行分析。 质谱（GC/MS）和液相色谱/MS/MS。将使用标准品进行鉴别。 由风味化学品形成的RxP将与来自EC溶剂的RxP明确区分。 目标2（哥伦比亚大学）。使用实验室制备的含有确定的DFC的液体制成的Vape气雾剂将由 一系列器械，并在剂量反应实验中使用体外试验筛选细胞毒性， 与来自正常成人的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平台的气液界面暴露系统进行深入研究， 重现人类呼吸道上皮。将使用六种癌症相关模式对个体DFC进行测试， 作用测定，包括上皮间质转化（EMT）的测定，我们已经观察到， 一些产品。将使用RNA-seq和受影响的途径确定基因表达的改变 鉴定DFC的混合物将以与消费品中相同的相对比例进行测试。 目标3（哥伦比亚大学）。由于目标2将检查热生成的气溶胶，因此DFC及其RxP产品将具有 一直在场。目标3将通过将3D EpiAirway平台暴露于 在没有加热的情况下产生的气溶胶，含有单独的DFC或加热产生的识别出的RxP。端点 试验将按照目标2进行，以分离单个化学品的毒性。 摘要人们对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 与全面新数据之间存在重大信息差距。将确定特定的毒物， 将对混合DFC进行评估。结果将被张贴在一个在线数据库，将访问任何 感兴趣的人或组织，并将提供基础信息，为未来的了解风味 烟草制品中的化学物质。这些数据是此类数据中的第一个，将有助于建立科学基础， 国家卫生研究院可以开发未来的研究方向，以保护消费者的健康， 通过第二和第三手的手段。