Metals in Electronic Cigarette Aerosol

描述（由申请人提供）：由于电子烟在不燃烧烟草的情况下提供尼古丁，因此它们可能为无法打破尼古丁成瘾的吸烟者提供有价值的替代品。然而，人们对电子烟的排放或其产生的健康问题知之甚少。我们的长期目标是了解电子烟如何影响人类健康，并为制定合理的电子烟生产、广告和销售政策提供科学依据。 我们的初步数据表明，来自领先品牌电子烟的气溶胶中含有高浓度的金属和金属纳米颗粒。拟议研究的目标是从广泛的产品和设计中识别和量化电子烟气溶胶的金属含量，检查含有金属含量的气溶胶的细胞毒性和遗传毒性，并检查人类电子烟使用者中金属暴露和影响的生物标志物。在我们的第一个特定目标中，我们将识别和量化各种品牌和款式的电子烟中的金属，并确定金属浓度与电子烟设计的关系。将使用电感耦合等离子体发射光谱法（ICP-OES）进行金属定量。将使用扫描和透射电子显微镜结合能量色散X射线光谱法（EDS）对颗粒结构和尺寸进行表征，以识别元素。气溶胶中的金属浓度将被检查作为一个功能的膨化拓扑结构。在第二个特定目标中，我们将使用MTT和彗星试验结合新型肝细胞代谢试验，确定含金属的气雾剂是否在人体细胞中产生细胞毒性和遗传毒性效应。人类胚胎干细胞将用于模拟产前发育的早期阶段，暴露于空气-液体界面的三维人类支气管/上皮组织将用于模拟人类肺暴露。在目标1和目标2中，电子香烟中的金属将与三种流行品牌的可燃香烟中的金属进行比较。在目标3中，我们将使用金属生物标志物来量化使用电子烟的人的金属暴露和影响，确定细胞吸收的金属是否包括纳米颗粒，并确定金属是否迁移到血液中并通过尿液排出。我们的项目将产生关于以下方面的新数据：（1）电子烟气雾剂在广泛的不断发展的产品中的金属含量，（2）电子烟气雾剂中金属的细胞/遗传毒性，（3）胚胎和分化的成年肺细胞对电子烟气雾剂金属的敏感性，以及（4）吸收， 排泄，以及金属在人类电子烟使用者中的生物效应。这些数据是此类数据中的第一个，将为FDA制定监管政策以保护消费者健康并最大限度地减少未来的公共卫生问题奠定科学基础。

DESCRIPTION (provided by applicant): Because electronic cigarettes deliver nicotine without burning tobacco, they may offer a valuable alternative for smokers who cannot break their nicotine addiction. However, little is known about electronic cigarette emissions or the health problems they produce. Our long-term objectives are to understand how electronic cigarettes affect human health and to contribute to the scientific foundation that will be used to establish rational policies for regulating the manufacture, advertisement, and sale of electronic cigarettes. Our Preliminary Data demonstrate high concentrations of metals and metal nanoparticles in aerosol from a leading brand of electronic cigarette. The goal of the proposed research is to identify and quantify the metal content of electronic cigarette aerosols from a broad spectrum of products and designs, to examine the cytoxicity and genotoxicity of aerosols with metal content, and to examine biomarkers of metal exposure and effect in human electronic cigarette users. In our first Specific Aim, we will identify and quantify metals in electronic cigarettes from various brands and styles and determine how metal concentrations correlate with electronic cigarette design. Metal quantification will be done using inductively coupled plasma-optical emission spectroscopy (ICP-OES). Characterization of particle structure and size will be done using scanning and transmission electron microscopy coupled with energy dispersive X-ray spectroscopy (EDS) to identify elements. Metal concentrations in aerosol will be examined as a function of puffing topology. In the second Specific Aim, we will determine if aerosols with metals produce cytotoxic and genotoxic effects in human cells using the MTT and comet assays, in combination with a novel liver cell metabolizing assay. Human embryonic stem cells will be used to model an early stage of prenatal development and three dimensional human bronchial/epithelial tissue exposed at an air-liquid interface will be used to model human lung exposure. In Aims 1 and 2, metals in electronic cigarettes will be compared to metals in three popular brands of combustible cigarettes. In Aim #3, we will use metal biomarkers to quantify metal exposure and effect in humans who use electronic cigarettes, determine if metal uptake by cells includes nanoparticles, and determine whether metals migrate to the bloodstream and are excreted in the urine. Our project will generate new data on: (1) the metal content of electronic cigarette aerosols across a broad spectrum of evolving products, (2) the cyto/genotoxicity of the metals in electronic cigarette aerosols, (3) the sensitivity of embryonic and differentiated adult lung cells to electronic cigarette aerosol metals, and (4) the absorption, excretion, and the biological effects of metals in human electronic cigarette users. These data, the first of their kind, will contribute to a foundation of science upon which the FDA can develop regulatory policies to protect consumers' health and minimize future public health problems.