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Synthetic cooling agent in oral nicotine pouch products marketed as ‘Flavour-Ban Approved’
  1. Sairam V Jabba1,2,
  2. Hanno C Erythropel2,3,
  3. Jackson G Woodrow4,
  4. Paul T Anastas5,6,
  5. Stephanie O'Malley2,7,
  6. Suchitra Krishnan-Sarin2,7,
  7. Julie B Zimmerman2,3,
  8. Sven Eric Jordt1,2
  1. 1Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina, USA
  2. 2Yale Tobacco Center of Regulatory Science, Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut, USA
  3. 3Chemical and Environmental Engineering, Yale University, New Haven, Connecticut, USA
  4. 4Yale College, New Haven, Connecticut, USA
  5. 5Center for Green Chemistry & Green Engineering, Yale University, New Haven, Connecticut, USA
  6. 6Department of Forestry and Environmental Studies, Yale University, New Haven, Connecticut, USA
  7. 7Psychiatry, Yale School of Medicine, New Haven, Connecticut, USA
  1. Correspondence to Dr Sven Eric Jordt, Department of Anesthesiology, Duke University School of Medicine, Durham NC 27710-3094, USA; sven.jordt{at}


Background US sales of oral nicotine pouches (ONPs) have rapidly increased, with cool/mint-flavoured ONPs the most popular flavour category. Restrictions on sales of flavoured 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 ‘Flavour-Ban Approved’ or ‘unflavoured’, probably to evade flavour bans and increase product appeal. At present, it is unclear whether these ONPs are indeed free of flavour additives that can impart pleasant sensations such as cooling.

Methods Sensory cooling and irritant activities of ‘Flavour-Ban Approved’ Zyn ONPs, Chill and Smooth, along with minty varieties (Cool Mint, Peppermint, Spearmint, Menthol), were analysed by Ca2+ microfluorimetry in HEK293 cells expressing the cold/menthol (TRPM8) or menthol/irritant receptor (TRPA1). Flavour chemical content of these ONPs was analysed by gas chromatography/mass spectrometry.

Results Zyn Chill ONP extracts robustly activated TRPM8, with much higher efficacy (39%–53%) than the mint-flavoured ONPs. In contrast, mint-flavoured ONP extracts elicited stronger TRPA1 irritant receptor responses than Chill extracts. Chemical analysis demonstrated that Chill exclusively contained WS-3, an odourless synthetic cooling agent, while mint-flavoured ONPs contained WS-3 together with mint flavourants.

Conclusions ONP products marketed as ‘Flavour-Ban Approved’ or ‘unflavoured’ contain flavouring agents, proving that the manufacturer’s advertising is misleading. Synthetic coolants such as WS-3 can provide a robust cooling sensation with reduced sensory irritancy, thereby increasing product appeal and use. Regulators need to develop effective strategies for the control of odourless sensory additives used by the industry to bypass flavour bans.

  • nicotine
  • non-cigarette tobacco products
  • tobacco industry

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  • Twitter @SairamJabba, @sejordt

  • SVJ and HCE contributed equally.

  • Correction notice The article has been corrected since it was published online. The equal contributorship information was missing which has been reinstated as SVJ and HCE contributed equally.

  • Contributors SVJ, HCE and SEJ conceptualised and designed the study; SK-S and SO'M provided advice on product choice. JGW and HCE acquired and analysed the chemical analytical data, supervised by PTA and JBZ. SVJ acquired, analysed and interpreted the data for calcium imaging and receptor activity experiments, supervised by SEJ; SVJ, SEJ and HCE drafted the manuscript. All authors critically reviewed, edited and approved the final manuscript. SEJ attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

  • Funding This work was supported by grant R56DA055996 to SEJ and cooperative agreement U54DA036151 (Yale Tobacco Center of Regulatory Science) to SK-S and SO'M from the National Institute on Drug Abuse of the National Institutes of Health, and the US Food and Drug Administration Center for Tobacco Products.

  • Disclaimer The funding organisation had no role in the design and conduct of the study; the collection, management, analysis and interpretation of the data; the preparation, review or approval of the manuscript; nor in the decision to submit the manuscript for publication. The content is solely the responsibility of the authors and does not necessarily represent the views of National institutes of Health or the Food and Drug Administration.

  • Competing interests Outside of the submitted work, SO'M reports being a member of the American Society of Clinical Psychopharmacology’s Alcohol Clinical Trials Initiative, supported by Alkermes, Dicerna, Ethypharm, Lundbeck, Mitsubishi Tanabe, Otsuka; consultant/advisory board member, Alkermes, Dicerna, Opiant; medication supplies, Novartis; DSMB member for National Institute on Drug Abuse Clinical Trials Network, Emmes and has been involved in a patent application with Novartis and Yale. The other authors have no disclosures to report.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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