Nicotine Pouches: Chemical Composition, Toxicity and Behavioral Effects of a New Tobacco Product Category

尼古丁袋：新型烟草产品类别的化学成分、毒性和行为影响

• 批准号: 10673370
• 负责人: SVEN-ERIC JORDT
• 金额: $ 41.65万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10673370
• 关键词: Address; Adolescent; Advertising; Antioxidants; Artificial Saliva; Behavior; Behavioral; Behavioral Model; Berry; Biological Assay; Candy; Categories; Cell Culture Techniques; Cell Line; Cells; Characteristics; Chemicals; Chemistry; Child; Cinnamon - dietary; Citrus; Coffee; Color; Consumption; Data; Electronic cigarette; Engineering; Epithelial Cells; Exposure to; Filler; Flavoring; Formulation; Gas Chromatography; Genes; Genetic Transcription; Genus Mentha; Goals; Health; Human; Inflammatory; Kinetics; Lip structure; Mentha spicata; Menthol; Metabolic; Mission; Mitochondria; Modeling; Mouse Strains; Mus; Nicotine; Oral cavity; Oral health; Oral mucous membrane structure; Pattern; Plant Leaves; Powder dose form; Property; Public Health; Publishing; Risk; Rodent; Role; Salts; Smokeless; Smokeless Tobacco; Source; Spectrum Analysis; Sugar Alcohols; Sweetening Agents; Taste Buds; Testing; Time; Tobacco; Tobacco Industry; Toxic effect; Toxicology; Work; Youth; aqueous; base; cytotoxic; design; drinking; experimental study; nicotine use; novel; oral cavity epithelium; preference; prevent; receptor; sex; snus; sweet taste perception; tobacco flavor; tobacco products; tobacco user; tobacco-free

Nicotine pouches are a rapidly growing new smokeless tobacco product category introduced to the US market in 2019 by several tobacco companies. Nicotine pouches contain a white powder, claimed to be tobacco-free, consisting of filler, tobacco-sourced nicotine or nicotine salts, sweeteners and a variety of flavors. These include mint, menthol, wintergreen and sweet-associated flavors (fruity and candy flavors such as berry, citrus, cinnamon, coffee), marketed in color patterns resembling advertising for popular electronic cigarette brands, raising concerns that children and adolescents might be drawn to this new product category. Nicotine pouches are marketed with claims of reduced risk and enable consumers to discretely consume nicotine. Currently, only limited data are available about their exact chemical composition, their behavioral and addictive effects or toxicological properties. In this proposal, we hypothesize that: (i) product design and formulation of this novel smokeless tobacco product category enables efficient and fast release of nicotine, flavorants and sweeteners; (ii) flavorants released from nicotine pouches have adverse oral health effects; and (iii) flavorants and sweeteners in nicotine pouches facilitate and increase product use initiation. These hypotheses are based on our published work and preliminary data demonstrating that nicotine pouch products contain significant amounts of synthetic high-intensity sweeteners. These sweeteners facilitated consumption of nicotine pouch extracts in naïve mice. The extracts proved cytotoxic and compromised mitochondrial function in an oral epithelial cell line model, suggesting metabolic toxicity. The following Specific Aims are pursued: Aim 1: Analyze chemical composition of nicotine pouch products and evaluate nicotine and flavorant release. Aim 2: Examine the toxicological effects of nicotine pouch extracts on oral epithelial cells. Aim 3: Examine the effects of synthetic sweeteners and flavors in nicotine pouches on preference behavior in mice This proposal addresses key domains critical to the mission of the FDA CTP, including chemistry and Engineering, Toxicity, Behavior and Health Effects (Effects of product design characteristics, sweeteners, flavors and flavor changes on initiation, nicotine consumption, and oral health). If our hypotheses are confirmed the project will provide a rationale for FDA to regulate levels of sweeteners, flavors and other constituents in nicotine pouch products, thereby reducing the public health impact of this novel tobacco product category.

尼古丁袋是一种迅速发展的新的无烟烟草产品类别，该产品介绍给美国市场 2019年由几家烟草公司组成。尼古丁小袋含有白色粉末，据称不含烟草， 由填充剂，烟草食用的尼古丁或尼古丁盐，甜味剂和各种口味组成。这些包括 薄荷，薄荷醇，冬绿色和甜味相关的口味（果味和糖果香气，例如浆果，柑橘，柑橘， 肉桂，咖啡），以类似于流行电子烟品牌广告的颜色销售， 提出担心儿童和青少年可能被吸引到这个新产品类别。尼古丁小袋 以降低风险的要求，使消费者能够离散食用尼古丁。目前，只有 有关其确切的化学成分，其行为和添加剂效应或 毒理学特性。 在此提案中，我们假设：（i）这种新型无烟烟草产品的产品设计和配方 类别可有效且快速释放尼古丁，口味和甜味剂； （ii）从 尼古丁袋具有不良的口腔健康影响； （iii）尼古丁袋中的口味和甜味剂 促进并增加产品使用计划。这些假设是基于我们发表的工作和初步的 数据表明尼古丁小袋产品包含大量合成高强度 甜味剂。这些甜味剂准备了幼稚小鼠中尼古丁袋提取物的消耗。提取物 在口腔上皮细胞系模型中证明了细胞毒性和受损的线粒体功能，这表明 代谢毒性。追求以下具体目标： AIM 1：分析尼古丁小袋产品的化学成分并评估尼古丁和风味释放。 目标2：检查尼古丁袋提取物对口腔上皮细胞的毒理作用。 目标3：检查尼古丁小袋中合成甜味剂和口味对偏好行为的影响 老鼠 该提案解决了对FDA CTP任务至关重要的关键领域，包括化学和 工程，毒性，行为和健康影响（产品设计特征，甜味剂，口味的影响 以及启动，尼古丁消耗和口腔健康的风味变化）。如果我们的假设得到确认 项目将为FDA提供基本原理，以调节尼古丁的甜味剂，口味和其他成分的水平 小袋产品，从而减少了这种新颖的烟草产品类别的公共卫生影响。