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.

尼古丁袋是一种快速增长的新型无烟烟草产品类别，于 2017 年引入美国市场。 2019年，多家烟草公司推出的尼古丁袋装含有白色粉末，声称不含烟草， 由填充剂、烟草源尼古丁或尼古丁盐、甜味剂和各种香料组成。 薄荷、薄荷醇、冬青和甜味相关风味（水果和糖果风味，如浆果、柑橘、 肉桂、咖啡），以类似于流行电子烟品牌广告的颜色图案进行销售， 引起人们对儿童和青少年可能会被这种新产品类别吸引的担忧。 目前，这些产品声称可以降低风险并允许消费者谨慎消费尼古丁。 关于其确切的化学成分、行为和成瘾作用的数据有限，或者 毒理学特性。 在此提案中，我们追求：（i）这种新型无烟烟草产品的产品设计和配方 该类别能够有效、快速地释放尼古丁、调味剂和甜味剂；(ii) 释放的调味剂； 尼古丁袋对口腔健康有不良影响；以及 (iii) 尼古丁袋中的调味剂和甜味剂 这些假设基于我们已发表的工作和初步成果。 数据表明尼古丁袋装产品含有大量合成高强度尼古丁 这些甜味剂促进了幼鼠对尼古丁袋提取物的消耗。 在口腔上皮细胞系模型中证明具有细胞毒性和线粒体功能受损，表明 代谢毒性的具体目标如下： 目标 1：分析尼古丁袋产品的化学成分并评估尼古丁和香料的释放。 目标 2：检查尼古丁袋提取物对口腔上皮细胞的毒理学影响。 目标 3：检查尼古丁袋中的合成甜味剂和香料对人们偏好行为的影响 老鼠 该提案涉及对 FDA CTP 使命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（产品设计特性、甜味剂、风味的影响 如果我们的假设得到证实，那么味道会随着起始、尼古丁消耗和口腔健康而变化。 该项目将为 FDA 监管尼古丁中甜味剂、香料和其他成分的含量提供依据 袋装产品，从而减少这种新型烟草产品类别对公共健康的影响。