Jabba Sairam V, Erythropel Hanno C, Woodrow Jackson G, Anastas Paul T, O'Malley Stephanie S, Krishnan-Sarin Suchitra, Zimmerman Julie B, Jordt Sven E
Department of Anesthesiology, Duke University School of Medicine, Durham, NC.
Yale Tobacco Center of Regulatory Science, Department of Psychiatry, Yale School of Medicine, New Haven, CT.
bioRxiv. 2023 Feb 24:2023.02.23.529797. doi: 10.1101/2023.02.23.529797.
US sales of oral nicotine pouches (ONPs) have rapidly increased, with cool/mint-flavored ONPs the most popular. Restrictions on sales of flavored tobacco products have either been implemented or proposed by several US states and localities. Zyn, the most popular ONP brand, is marketing Zyn-"Chill" and Zyn-"Smooth" as "Flavor-Ban Approved", probably to evade flavor bans. At present it is unclear whether these ONPs are indeed free of flavor additives that can impart pleasant sensations such as cooling.
Sensory cooling and irritant activities of "Flavor-Ban Approved" ONPs, Zyn-"Chill" and "Smooth", along with "minty" varieties (Cool Mint, Peppermint, Spearmint, Menthol), were analyzed by Ca2+ microfluorimetry in HEK293 cells expressing the cold/menthol (TRPM8) or menthol/irritant receptor (TRPA1). Flavor chemical content of these ONPs was analyzed by GC/MS.
Zyn-"Chill" ONP extracts robustly activated TRPM8, with much higher efficacy (39-53%) than the mint-flavored ONPs. In contrast, mint-flavored ONP extracts elicited stronger TRPA1 irritant receptor responses than Zyn-"Chill" extracts. Chemical analysis demonstrated the presence of WS-3, an odorless synthetic cooling agent, in Zyn-"Chill" and several other mint-flavored Zyn-ONPs.
Synthetic cooling agents such as WS-3 found in 'Flavor-Ban Approved' Zyn-"Chill" can provide a robust cooling sensation with reduced sensory irritancy, thereby increasing product appeal and use. The label "Flavor-Ban Approved" is misleading and may implicate health benefits. Regulators need to develop effective strategies for the control of odorless sensory additives used by the industry to bypass flavor bans.
美国口服尼古丁袋（ONP）的销量迅速增长，其中清凉/薄荷味的ONP最受欢迎。美国几个州和地方已经实施或提议对调味烟草产品的销售进行限制。最受欢迎的ONP品牌Zyn将Zyn-“Chill”和Zyn-“Smooth”宣传为“经口味禁令批准”，可能是为了规避口味禁令。目前尚不清楚这些ONP是否确实不含能带来清凉等愉悦感觉的调味添加剂。
通过Ca2+ 微荧光法在表达冷/薄荷醇（TRPM8）或薄荷醇/刺激受体（TRPA1）的HEK293细胞中分析“经口味禁令批准”的ONP（Zyn-“Chill”和“Smooth”）以及“薄荷味”品种（清凉薄荷味、薄荷味、留兰香味、薄荷醇味）的感官清凉和刺激活性。通过气相色谱/质谱联用仪（GC/MS）分析这些ONP的风味化学成分。
Zyn-“Chill”ONP提取物能强烈激活TRPM8，其功效（39 - 53%）远高于薄荷味ONP。相比之下，薄荷味ONP提取物比Zyn-“Chill”提取物引发更强的TRPA1刺激受体反应。化学分析表明，Zyn-“Chill”和其他几种薄荷味Zyn-ONP中存在一种无味合成清凉剂WS-3。
在“经口味禁令批准”的Zyn-“Chill”中发现的WS-3等合成清凉剂能提供强烈的清凉感，同时减少感官刺激，从而增加产品吸引力和使用量。“经口味禁令批准"这一标签具有误导性，可能暗示有益健康。监管机构需要制定有效的策略来控制该行业使用的无味感官添加剂，以绕过口味禁令。
