Influence of Mint Flavorings and pH on Nicotine Absorption in Smokeless Tobacco

描述（由申请人提供）：拟议的研究代表了无烟烟草（卷烟）产品中薄荷香料的首次系统调查。将确定pH值和薄荷调味剂（薄荷醇和冬青）对尼古丁的主要影响和相互作用。将对鉴定为薄荷味（目标1）的市售可得的薄荷产品的全面样品进行pH值和调味成分的定量分析。这些信息将用于确定pH值和调味剂浓度范围，以修改非调味研究参考产品（目标2）。在一项双盲、受试者内实验设计（目标3）中，有经验的尼古丁使用者将在实验室中使用这些改良产品，以检查pH值和薄荷调味剂对尼古丁吸收的影响。参与者将被随机分配到两个薄荷组（薄荷醇或冬青）之一，并将参与5个实验阶段：1）参考产品，2）高pH值，低薄荷，3）高pH值，高薄荷，4）低pH值，低薄荷，和5）低pH值，高薄荷。主要结局变量将是尼古丁暴露、心血管效应以及对体验和产品特性的主观评价。过去的研究依赖于商业产品之间的比较。尽管可根据感兴趣的特性（例如pH值）选择可降解产品，但可能存在其他未知和混淆的添加剂。这种担忧是避免在拟议的研究中，一个单一的参考产品将通过添加调味剂和化合物改变pH值的参数修正。从目前的研究结果将告知公共卫生界流行的调味剂对尼古丁暴露的影响，并提供一个新的模型来研究尼古丁产品，以帮助那些负责任地指导烟草监管通过循证知识。

DESCRIPTION (provided by applicant): The proposed research represents the first systematic investigation of mint flavorings in smokeless tobacco (SLT) products. Main and interactive effects of pH and mint flavorings (menthol and wintergreen) on nicotine will be identified. A comprehensive sample of commercially available SLT products identified as mint flavored (Aim 1) will quantitatively analyzed for pH and flavoring components. The information will be used to determine ranges of pH and flavoring concentrations to amend a non-flavored research SLT referent product (Aim 2). In a double-blind, within-subject experimental design (Aim 3), experienced SLT users will utilize these amended products in the laboratory to examine the effects of pH and mint flavorings on nicotine absorption. Participants will be randomized to one of two mint groups (menthol or wintergreen) and will engage in 5 experimental sessions: 1) referent product, 2) high pH, low mint, 3) high pH, high mint, 4) low pH, low mint, and 5) low pH, high mint. The main outcome variables will be nicotine exposure, cardiovascular effects and subjective evaluations of the experience and product characteristics. Past studies have relied upon comparisons between commercial products. Although SLT products can be selected on a characteristic of interest (for example, pH), there may be other unknown and confounding additives present. This concern is obviated in the proposed research where a single referent product will be parametrically amended by the addition of flavorings and compounds to change pH. Results from the present study will inform the public health community about the effects of popular flavorings on nicotine exposure and offer a new model to study SLT products to assist those who responsibly guide tobacco regulation through evidenced-based knowledge.