Synthetic Cooling Agent in Oral Nicotine Pouch Products Marketed as "Flavor-Ban Approved"

Introduction:
This text is a summary of a scientific study examining the use of synthetic cooling agents in oral nicotine pouch (ONP) products marketed as "Flavor-Ban Approved." The study aimed to determine if these products are indeed free of flavor additives and to investigate the presence of synthetic odorless cooling agents and mint flavorants in these products.

Key Points:

* The study analyzed ONP extracts for activity on the human cold/menthol receptor (TRPM8) and the menthol irritant receptor (TRPA1) using calcium microfluorimetry.
* Zyn-"Chill" extracts exhibited a higher efficacy for TRPM8 activation compared to mint-/menthol-flavored ONP extracts and a nicotine dilution series.
* Zyn-"Chill" extracts showed significantly weaker TRPA1 activation compared to mint-flavored ONP extracts, indicating the presence of a non-irritating cooling ingredient.
* Chemical analysis of ONP extracts demonstrated the presence of WS-3, an odorless menthol-derived synthetic cooling agent, in Zyn-"Chill" and several other mint-flavored Zyn ONPs.
* WS-3 was present in higher concentrations in Zyn-"Chill" (234±7µg/pouch) compared to Zyn-Peppermint (201±11 µg/pouch) and Zyn-Spearmint (209±15 µg/pouch).
* Other minty flavorants were detected in Zyn-Peppermint and Zyn-Spearmint, but not in Zyn-Cool Mint or Zyn-Menthol.
* Zyn-Smooth did not contain any cooling or mint flavorants.

Main Message:
The study found that synthetic cooling agents such as WS-3 are added to several tested cool-/mint-flavored Zyn ONPs, including Zyn-Chill, an ONP advertised as "Flavor-Ban Approved." These agents likely provide a robust oral cooling sensation by strongly activating TRPM8 and reducing irritation by weakening TRPA1 activation, thereby increasing the appeal of the product. The use of the "Flavor-Ban Approved" moniker may be misleading to consumers who may perceive these products as healthier, despite the presence of additives that modify sensory product perception. Regulations on characterizing flavors that rely on odor perception may provide a loophole for the tobacco industry to add odorless sensory chemicals such as synthetic cooling agents, and alternative approaches to regulate synthetic cooling agents should be considered.

Jabba, S. V., Erythropel, H. C., Woodrow, J. G., Anastas, P. T., O’Malley, S. S., Krishnan-Sarin, S., Zimmerman, J. B., & Jordt, S. E. (2023). Synthetic Cooling Agent in Oral Nicotine Pouch Products Marketed as “Flavor-Ban Approved.” bioRxiv: The Preprint Server for Biology, 2023.02.23.529797. https://doi.org/10.1101/2023.02.23.529797