Electronic cigarettes: do they present health hazards?

电子烟：它们对健康有害吗？

• 批准号: 8597948
• 负责人: Rachel Zarina Behar
• 金额: $ 3.44万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8597948
• 关键词: Adult; Advertising; Aerosols; Affect; Alkaline Single-Cell Gel Electrophoresis Assay; Antibodies; Apoptosis; Apoptotic; Atomizer; Biological Assay; Breathing; Cell Survival; Cells; Chemicals; Cigarette; Communities; DNA; DNA Damage; Data; Detection; Development; Devices; Dose; Electronics; Embryo; Environment; Family Smoking Prevention and Tobacco Control Act; Fibroblasts; Flavoring; Food Additives; Foundations; Goals; Health; Health Hazards; Heating; Housing; Human; Human Development; Incubated; Lead; Liquid substance; Lung; Magic; Manufacturer Name; Mass Fragmentography; Modeling; Nicotine; Organ; Organic Chemicals; Oxidative Stress; Pathway interactions; Perfume; Pluripotent Stem Cells; Poison; Policies; Property; Propylene Glycols; Proteins; Public Health; Reactive Oxygen Species; Reproduction; Research; Research Training; Running; Sampling; Science; Smoking; Solutions; Staining method; Stains; Study models; Testing; Time; Tobacco; Toxic effect; United States National Institutes of Health; Vitamin E; Western Blotting; Work; annexin A5; base; caspase-3; cell type; chemical standard; cigarette smoking; cytotoxic; cytotoxicity; detector; genotoxicity; human embryonic stem cell; immunocytochemistry; improved; inhibitor/antagonist; insight; prenatal; public health relevance; research study; response; screening; smoking cessation; time use; toxicant; trend

DESCRIPTION (provided by applicant): *Square brackets [--] indicate parts of the Research Training Plan that have been changed* Electronic cigarettes (EC) are nicotine delivery devices, often advertised for smoking cessation. Recently released into the consumer marketplace, EC devices are quickly becoming popular worldwide. EC parts include: a mouthpiece housing a cartridge of nicotine-containing fluid, an atomizer used for heating, and a battery. The cartridge fluids vary, typically containing some concentration of nicotine, a humectant, such as propylene glycol, and various flavorings. One visible trend in the EC community is to refill the nicotine solution by dripping refill fluid into an empty cartridge. In spite of EC growing popularity, few scientific studies have been conducted to assess possible health effects of EC aerosol on users or bystanders, and it remains unclear if EC pose a health concern. Flavorings used in EC are often food additives and perfumes, which are not intended to be heated and inhaled and which have unknown consequences on human health. My long-term objective is to characterize the effects of EC use on human health. This proposal specifically focuses on the cytotoxicity of EC refill fluid aerosol. I will first (Aim #1) use human embryonic stem cells (hESC) and human pulmonary fibroblasts (hPF) to evaluate the cytotoxicity of EC refill fluid aerosols from different manufacturers. Screening for cytotoxicity will be done using the MTT cell viability assay and a metabolizing assay. This first step will identify EC products that may produce adverse health effects in humans. Secondly (Aim #2), I will use gas chromatography and mass spectrometry to identify toxic chemicals in EC aerosols. Each chemical identified will then be purchased and analyzed using the MTT assay with hESC and hPF. Identification of toxicants in these products would allow manufacturers to remove them and make users aware of potentially dangerous products. I will then create a hierarchy of potency for EC refill fluid aerosols and the identified chemicals. [Finally, I will test the hypothesis that EC aerosols and the identified chemicals induce reactive oxygen species (ROS), which lead to DNA damage and apoptosis. To test this (Aim #3), the most cytotoxic aerosols and chemicals will be screened with and without vitamin E (a ROS inhibitor) to assess induction of ROS using time-lapse data and fluorescent ROS detectors. To determine if increased ROS leads to DNA damage, the alkaline comet assay and immunocytochemistry will be used to assess breaks in DNA. For aerosols and chemicals that induce oxidative stress and are genotoxic, time-lapse data will be analyzed for hESC and hPF in conjunction with apoptotic indicators. Western blotting and the Annexin V assays will be used to verify activation of the apoptotic pathway proteins.] This will be the first large-scale assessment of cytotoxicity in EC refill fluid aerosols. The proposed study will collect valuable data that wil provide insight into which of these products are unsafe, the doses that produce cytotoxic and genotoxic effects, the specific chemicals that are toxic, and finally, which products are likely to adversely affect the health of users.

描述（由申请人提供）：* 方括号[--]表示研究培训计划中已更改的部分 * 电子烟（EC）是尼古丁输送装置，通常宣传用于戒烟。最近被投放到消费者市场，EC设备正在全球范围内迅速流行。EC部件包括：容纳含尼古丁流体的药筒的烟嘴、用于加热的雾化器和电池。烟弹流体变化，通常含有一定浓度的尼古丁、湿润剂（例如丙二醇）和各种调味剂。EC群体中的一个明显趋势是通过将再填充流体滴入空药筒中来再填充尼古丁溶液。尽管氨基甲酸乙酯越来越受欢迎，但很少进行科学研究来评估氨基甲酸乙酯气雾剂对使用者或旁观者可能产生的健康影响，目前尚不清楚氨基甲酸乙酯是否会造成健康问题。欧盟委员会使用的调味品通常是食品添加剂和香料，这些调味品不能加热和吸入，对人体健康的影响未知。我的长期目标是描述EC使用对人类健康的影响。本提案特别关注EC再填充液气雾剂的细胞毒性。我将首先（目的#1）使用人胚胎干细胞（hESC）和人肺成纤维细胞（HPF）评价来自不同组织的EC再填充液气雾剂的细胞毒性。 厂商将使用MTT细胞活力试验和代谢试验进行细胞毒性筛选。这第一步将确定可能对人类健康产生不良影响的EC产品。其次（目标2），我将使用气相色谱和质谱法来识别EC气溶胶中的有毒化学物质。然后购买鉴定的每种化学物质，并使用hESC和hPF进行MTT试验进行分析。识别这些产品中的有毒物质将使制造商能够去除它们，并使用户意识到潜在的危险产品。然后，我将创建一个层次的效力EC填充液气雾剂和确定的 化学品[最后，我将检验EC气溶胶和已确定的化学物质诱导活性氧簇（ROS），从而导致DNA损伤和细胞凋亡的假设。为了测试这一点（目标#3），将在有和没有维生素E（ROS抑制剂）的情况下筛选最具细胞毒性的气溶胶和化学品，以使用延时数据和荧光ROS检测器评估ROS的诱导。为了确定增加的ROS是否导致DNA损伤，将使用碱性彗星试验和免疫细胞化学来评估DNA断裂。对于诱导氧化应激和遗传毒性的气溶胶和化学物质，将结合凋亡指标分析hESC和HPF的延时数据。将使用蛋白质印迹法和膜联蛋白V测定来验证凋亡途径蛋白的激活。]这将是第一次大规模的评估 EC填充液气雾剂的细胞毒性。拟议的研究将收集有价值的数据，这些数据将提供洞察这些产品是不安全的，产生细胞毒性和遗传毒性作用的剂量，有毒的具体化学物质，以及最后，哪些产品可能 对使用者的健康产生不利影响。