Synthetic cooling agents and nicotine analogs in new tobacco products: tobacco industry strategies to bypass regulation

Banning flavor additives and regulating nicotine content in tobacco products are key strategies by regulators to prevent smoking initiation, promote cessation and reduce health disparities. Tobacco companies recently introduced “non-menthol” cigarettes, resembling banned menthol cigarette brands. Electronic cigarette companies started marketing products with nicotine alternatives, claiming their products are exempt from regulation. Calcium-microfluorimetry in HEK293t cells expressing TRPM8-Cold/menthol receptors was used to determine whether extracts from “non-menthol” cigarettes produce sensory cooling effects. Gas-chromatography/mass-spectrometry was used to detect flavor chemicals, including synthetic cooling agents, in “non-menthol” cigarettes. Liquid chromatography/mass spectrometry was used to detect nicotine and nicotine analogs. Extracts from several “non-menthol” cigarettes activated cold/menthol receptors at higher dilutions and with stronger efficacies than menthol cigarettes. Chemical analysis detected the synthetic cooling agent, WS-3, in several “non-menthol” cigarette brands. 6-methyl nicotine, a structural analog of nicotine, was detected in e-cigarette products. Tobacco companies have added WS-3 to “non-menthol” cigarettes, a synthetic cooling agent that creates a cooling sensation similar to menthol but lacks menthol’s characteristic “minty” odor. A structural nicotine analog is used as a nicotine replacement in e-cigarettes. Regulators and legislators need to assess whether these products violate national regulations.