Rapid response human testing of smokeless tobacco products

描述（由申请人提供）：虽然成人吸烟率继续下降，但无烟烟草（ST）的使用正在增加。自2005年以来，几乎所有主要的卷烟生产商都进入了ST市场。一些生产商正在使用其流行的卷烟品牌名称（例如，万宝路鼻烟、骆驼鼻烟、好彩鼻烟）。这些新产品的扩散增加了已经广泛的非吸烟烟草（例如，湿鼻烟、嚼烟、iqmik、颗粒）。在如此快速变化的环境中表征这些ST产品需要比传统的长期交叉试验更快速的方法。这是一项应用急性试验措施的建议，以更好地了解人类使用不同ST产品的后果。我们将进行一系列急性交叉试验，系统地测试目前市场上的ST产品，以及在工作过程中引入的任何产品，以确定其滥用倾向和潜在毒性。 为此，我们提出了以下具体目标：描述和对比滥用责任的可能性和采用一系列ST产品的可能性。ST的滥用倾向评估（ALA）将包括喜好和渴望/戒断和神经认知功能的缓解（EEG频谱分析和事件相关电位）与药用尼古丁的比较（已知滥用可能性低的对照品）;为了使用对烟草产品的一次性使用敏感的加强生物标志物来表征和对比ST产品的潜在毒性，包括唾液中烟草特有的亚硝胺（TSNA）和多环芳烃（PAH）以及呼出气体中的挥发性有机化合物（VOC），所有这些都是在单次使用每种产品之前和之后测量的;以及通过测量一系列ST产品排放的VOC水平以及TSNA和PAH的产品水平来表征和对比ST产品的潜在毒性和滥用潜力，以及评估pH、水分、总尼古丁和游离尼古丁水平。

DESCRIPTION (provided by applicant): While rates of adult cigarette smoking continue to decline, smokeless tobacco (ST) use is increasing. Since 2005, virtually every major producer of cigarettes has entered the market for ST. Some are producing products using their popular cigarette brand names (e.g., Marlboro Snus, Camel Snus, Lucky Strike Snus). The proliferation of these new products is adding to the already wide array of available non-smoked tobacco (e.g., moist snuff, chewing tobacco, iqmik, pellets). Characterizing these ST products in such a rapidly changing landscape requires more rapid means than traditional long term cross-over trials. This is a proposal to apply acute testing measures to better understand the consequences of human use of varying ST products. We will perform a series of acute cross-over trials, systematically testing ST products currently on the market, and any introduced in the course of the work to determine their abuse liability and potential toxicity. To that end, we propose the following specific aims: To characterize and contrast the abuse liability potential and likelihood of adoption of a range of ST products. Abuse liability assessment (ALA) of ST will include liking and relief of craving/withdrawal and neurocognitive function (EEG spectral analysis and event- related potentials) in comparison to medicinal nicotine (control with known low abuse potential); to characterize and contrast the potential toxicity of ST products using boost biomarkers that are sensitive to one-time use of a tobacco product, including salivary tobacco-specific nitrosamines (TSNAs) and polycyclic aromatic hydrocarbons (PAHs) and exhaled breath volatile organic compounds (VOCs), all measured before and after single-use of each product; and, to characterize and contrast the potential toxicity and abuse potential of ST products by measuring levels of VOCs emitted from a range of ST products, as well as product levels of TSNAs and PAHs, and assessing pH, moisture, total nicotine, and free nicotine levels.