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加利福尼亚州销售的“非薄荷醇”香烟中的合成冷却剂和糖果口味。

Synthetic Cooling Agent and Candy Flavors in California-marketed "non-Menthol" Cigarettes.

作者信息

Jabba Sairam V, Erythropel Hanno C, Anastas Paul T, Zimmerman Julie B, Jordt Sven E

出版信息

bioRxiv. 2023 May 18:2023.05.15.540890. doi: 10.1101/2023.05.15.540890.

Abstract

RATIONALE

The ban of menthol cigarettes is one of the key strategies to promote smoking cessation in the United States. Menthol cigarettes are preferred by young beginning smokers for smoking initiation. Almost 90% of African American smokers use menthol cigarettes, a result of decades-long targeted industry marketing. Several states and municipalities already banned menthol cigarettes, most recently California, effective on December 21, 2022. In the weeks before California's ban took effect, the tobacco industry introduced several "non-menthol" cigarette products in California, replacing previously mentholated brands. Here, we hypothesize that tobacco companies replaced menthol with synthetic cooling agents to create a cooling effect without using menthol. Similar to menthol, these agents activate the TRPM8 cold-menthol receptor in sensory neurons innervating the upper and lower airways.

METHODS

Calcium microfluorimetry in HEK293t cells expressing the TRPM8 cold/menthol receptors was used to determine sensory cooling activity of extracts prepared from these "non-menthol" cigarette brands, and compared to standard menthol cigarette extracts of the same brands. Specificity of receptor activity was validated using TRPM8-selective inhibitor, AMTB. Gas chromatography mass spectrometry (GCMS) was used to determine presence and amounts of any flavoring chemicals, including synthetic cooling agents, in the tobacco rods, wrapping paper, filters and crushable capsule (if present) of these "non-menthol" cigarettes.

RESULTS

Compared to equivalent menthol cigarette extracts, several California-marketed "non-menthol" cigarette extracts activated cold/menthol receptor TRPM8 at higher dilutions and with stronger efficacies, indicating substantial pharmacological activity to elicit robust cooling sensations. Synthetic cooling agent, WS-3, was detected in tobacco rods of several of these "non-menthol" cigarette brands. Crushable capsules added to certain "non-menthol" crush varieties contained neither WS-3 nor menthol but included several "sweet" flavorant chemicals, including vanillin, ethyl vanillin and anethole.

CONCLUSION

Tobacco companies have replaced menthol with the synthetic cooling agent, WS-3, in California-marketed "non-menthol" cigarettes. WS-3 creates a cooling sensation similar to menthol, but lacks menthol's characteristic "minty" odor. The measured WS-3 content is sufficient to elicit cooling sensations in smokers, similar to menthol, that facilitate smoking initiation and act as a reinforcing cue. Regulators need to act quickly to prevent the tobacco industry from bypassing menthol bans by substituting menthol with synthetic cooling agents, and thereby thwarting smoking cessation efforts.

摘要

理论依据

禁止薄荷醇香烟是美国促进戒烟的关键策略之一。薄荷醇香烟是刚开始吸烟的年轻人的首选。由于烟草行业数十年的定向营销,近90%的非裔美国吸烟者使用薄荷醇香烟。几个州和直辖市已经禁止销售薄荷醇香烟,最近的是加利福尼亚州,于2022年12月21日生效。在加利福尼亚州禁令生效前的几周里,烟草行业在该州推出了几种“非薄荷醇”香烟产品,取代了之前的薄荷醇品牌。在此,我们假设烟草公司用合成冷却剂取代了薄荷醇,以在不使用薄荷醇的情况下产生清凉效果。与薄荷醇类似,这些物质会激活支配上下呼吸道的感觉神经元中的TRPM8冷-薄荷醇受体。

方法

利用表达TRPM8冷/薄荷醇受体的HEK293t细胞中的钙微荧光法,测定这些“非薄荷醇”香烟品牌提取物的感觉清凉活性,并与同一品牌的标准薄荷醇香烟提取物进行比较。使用TRPM8选择性抑制剂AMTB验证受体活性的特异性。气相色谱-质谱联用仪(GCMS)用于测定这些“非薄荷醇”香烟的烟杆、包装纸、过滤嘴和可碾碎胶囊(如有)中包括合成冷却剂在内的任何调味化学品的存在情况和含量。

结果

与同等的薄荷醇香烟提取物相比,几种在加利福尼亚州销售的“非薄荷醇”香烟提取物在更高稀释度下以更强的效力激活了冷/薄荷醇受体TRPM8,表明其具有引发强烈清凉感的显著药理活性。在其中几个“非薄荷醇”香烟品牌的烟杆中检测到了合成冷却剂WS-3。添加到某些“非薄荷醇”可碾碎品种香烟中的可碾碎胶囊既不含WS-3也不含薄荷醇,但含有几种“甜味”调味化学品,包括香草醛、乙基香草醛和茴香脑。

结论

烟草公司在加利福尼亚州销售的“非薄荷醇”香烟中用合成冷却剂WS-3取代了薄荷醇。WS-3产生的清凉感与薄荷醇类似,但没有薄荷醇特有的“薄荷味”。测得的WS-3含量足以在吸烟者中引发清凉感,类似于薄荷醇,这有助于吸烟起始并起到强化提示作用。监管机构需要迅速采取行动,防止烟草行业通过用合成冷却剂替代薄荷醇来规避薄荷醇禁令,从而挫败戒烟努力。

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