Identification and toxicity of chemicals that are linked to EVALI

与 EVALI 相关的化学物质的鉴定和毒性

• 批准号: 10115508
• 负责人: Prudence Talbot
• 金额: $ 17.65万
• 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/10115508
• 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; Link; 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 电子卷烟（ECS）使用热量将通常包含高浓度的“电子液体”混合物雾化 风味化学品。该项目将购买650个商业电子液体：a）识别和量化风味 使用的化学物质加上蒸发时形成的降解反应产物（RXP）； b）评估 细胞对这些风味化学物质的反应通常在> 1 mg/ml（即“主要风味化学物质”，DFC），DFCS中发现， 以及在蒸气时产生的气溶胶。经测试将为550个“流行”补充和菜单液和100液 据报道，这些引起用户的疾病。工作将在两个校园进行： 波特兰州立大学分析化学大学和加利福尼亚大学人类毒理学。 目标1（PSU）。 DFC和VAPING RXPS将被识别并定量650液。使用的气溶胶 将在异丙醇中收集各种功率的一系列设备，并使用气相色谱法/分析 质谱法（GC/MS）和液相色谱/MS/MS。标识将采用标准。 由风味化学品形成的RXP将与EC溶液明确区分RXP。 目标2（UCR）。使用含有识别DFC的实验室准备的流体制成的vape气溶胶将与 一系列设备，并在剂量反应实验中使用体外测定中的细胞毒性进行筛选 与正常人成年人的Beas-2b肺上皮细胞的联系。最细胞毒性的气溶胶 将使用3D Epiairway平台的空气接口曝光系统深入研究 概括人类呼吸道上皮。单个DFC将使用六个与癌症相关的模式进行测试 动作测定包括我们观察到的上皮到间充质转变（EMT）的测定 一些EC产品。基因表达的改变将使用RNA-seq并影响途径确定 确定。 DFC的混合物将以与消费产品相同的相对比例进行测试。 目标3（UCR）。由于AIM 2将检查产生的热气溶胶，因此DFC及其RXPS产品将具有 我们在场。 AIM 3将通过将3D Epiairway平台暴露于DFC和RXP毒性来区分 无热的气溶胶产生，包含单个DFC或从加热中鉴定出的RXP。端点 测定将如AIM 2中进行，以分离对单个化学物质的毒性。 概括。关于EC中使用的风味化学物质的健康影响知之甚少。这个项目将填补 重要的信息差距，并具有全面的新数据。将确定特定的毒物，并影响 将评估混合DFC的混合。结果将发布在在线数据库上，该数据库可访问任何 有兴趣的人或组织，并将提供基本信息，以便将来了解风味 烟草产品中的化学物质。数据是其中的第一个，将为科学的基础做出贡献 NIH可以开发未来的研究指示，以保护消费者的健康并保护那些暴露的人 通过第二和第三手手段。