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18C.4 Chemicals in oral nicotine products
Foreword

Relevant news and research: Chemicals in oral nicotine products

Ciancio, J. R., Kumar, L., Rastogi, K., Moran, M. B., Czaplicki, L., Page, M. K., Jamil, H., Goniewicz, M. L. and Spindle, T. R. (2026). Nicotine Analogues in Oral Pouch Products and Associated Marketing Claims. JAMA Netw Open, 1, e2554883. Available from: https://www.ncbi.nlm.nih.gov/pubmed/41569568


Jabba, S. V., Erythropel, H. C., Silinski, P., Mellinghoff, R. A., Anastas, P. T., Zimmerman, J. B. and Jordt, S. E. (2025). Health Risk Assessment for an Unregulated Neurotoxic Nicotine Analogue in Oral Pouch Products. medRxiv. Available from: https://www.ncbi.nlm.nih.gov/pubmed/41480030


Platt, S. P., Gonzales, C. M., Pokharel, P., Park, S. C., Sriram, A., Thorpe, S. B., Ritzenthaler, A. B. and Aldeek, F. (2026). Dissolution and physical characterization of oral nicotine pouch products. Sci Rep. Available from: https://www.ncbi.nlm.nih.gov/pubmed/41495155


Staaf, M., Masser, A. E., Pramfalk, C., Pendrill, R., Moses, S., Lindholm, J. and Ljung, T. (2026). Randomized studies assessing the effect of flavor on pharmacokinetic and subjective parameters for dry and moist nicotine pouches. Drug Alcohol Depend, 113050. Available from: https://www.ncbi.nlm.nih.gov/pubmed/41579531


Peraza, N., Thakur, R. S., Jabba, S. V., Aguilera, J., Martines, P. W., Brinkman, M. C., Jordt, S. E., El Hellani, A., Monterosso, J. R. and Tackett, A. P. (2025). Pre- and Post-Flavor Ban Oral Nicotine Pouches: A Chemical, Sensory, and Young Adult Appeal Analysis. medRxiv. Available from: https://www.ncbi.nlm.nih.gov/pubmed/41415510


Przulj, D., Smith, K. M., McRobbie, H., Pesola, F., Ananina, I., Ladmore, D. and Hajek, P. (2025). Nicotine delivery from and user reactions to nicotine pouches compared to cigarettes. Psychopharmacology (Berl). Available from: https://www.ncbi.nlm.nih.gov/pubmed/41384973


Heshmati, J., Bates, E. L., Shahen, S., Visintini, S., Quirouette, E., Mullen, K. A. and Mir, H. (2025). Nicotine pouch pharmacokinetics compared to smoked tobacco: A systematic review and meta-analysis. Drug Alcohol Depend Rep, 100389. Available from: https://www.ncbi.nlm.nih.gov/pubmed/41246258


Shin, H. S., Pyo, H., Oh, Y., Choi, K. Y., Vu, T. H. V., Kim, G. Y. and Park, D. (2026). Identification and quantitative analysis of impurities in tobacco-derived and synthetic nicotine: Is synthetic nicotine really safe and pure?. J Pharm Biomed Anal, 117221. Available from: https://www.ncbi.nlm.nih.gov/pubmed/41177108


Li, X. S., Sriram, A., Zhuang, S. M. and Aldeek, F. (2025). Evaluation of Factors Impacting Nicotine Permeation in Oral Nicotine Pouch Products. ACS Omega, 39, 45644-45655. Available from: https://www.ncbi.nlm.nih.gov/pubmed/41078756


Czaplicki, L., Moran, M. B., Kennedy, R. D., Tfayli, D., Frisbee, S., Ibrahim, M. and Spindle, T. R. (2025). Nicotine analogue pouches: a growing regulatory challenge. Tob Control. Available from: https://www.ncbi.nlm.nih.gov/pubmed/40789760


de Granda-Orive, J. I., Jimenez-Ruiz, C. A. and Farber, H. J. (2025). Unregulated and Addictive: The Silent Rise of Nicotine Analogues. Arch Bronconeumol. Available from: https://www.ncbi.nlm.nih.gov/pubmed/40816965


Xie, Z., Conklin, D. J., Jin, L., Miller, A., Stowers, H., Gallagher, J., Keith, R. J., Chen, J. Y. and Lorkiewicz, P. (2025). Characterizing Oxidative Metabolites of 6-Methylnicotine (6MN; aka metatine): Divergent Metabolism from Nicotine and Identification of Urinary Biomarkers of Exposure. Toxicol Sci. Available from: https://www.ncbi.nlm.nih.gov/pubmed/40690396


Comite? National Contre le Tabagisme (2025). The CNCT alerts on the use of a new addictive molecule used by the tobacco industry: 6-methyl-nicotine. . Available from: https://cnct.fr/wp-content/uploads/2025/05/Press-release-WNTD-1.pdf


GŽnŽration Sans Tabac (2025). The CNCT warns of 6-methyl-nicotine: a new addictive threat in vaping products and oral pouches. . Available from: https://www.generationsanstabac.org/en/actualites/le-cnct-alerte-sur-la-6-methyl-nicotine-une-nouvelle-menace-addictive-dans-les-produits-de-vapotage-et-sachets-oraux/


Page, M. K., Leigh, N. J., Block, A. C., Marrano, P. H., Travers, M. B., Adrover, J. E., Maley, G. E., Koenig, L. A., Salem, E. M., Heldwein, S. D. and Goniewicz, M. L. (2025). Comparison of Nicotine and Selected Flavorings Content Between Tobacco-Free and Tobacco-Containing Oral Pouches. Nicotine Tob Res. Available from: https://www.ncbi.nlm.nih.gov/pubmed/40383714


Pankow, J. F., Luo, W., McWhirter, K. J., Sengupta, M. and Strongin, R. M. (2025). Levels of the nicotine analog 6-methyl nicotine as a naturally formed tobacco alkaloid in tobacco and tobacco products. Sci Rep, 1, 17945. Available from: https://www.ncbi.nlm.nih.gov/pubmed/40410306


Cohen, J. E., Ibrahim, M., Saraf, S., Welding, K., Luo, W., McWhirter, K. J., Clegg Smith, K. and Pankow, J. F. (2025). Velo (BAT) buffet of oral nicotine pouches in Pakistan: varying brand variant levels of nicotine, menthol and other flavour chemicals. Tob Control. Available from: https://www.ncbi.nlm.nih.gov/pubmed/40216552


Kanobe, M. N., Powell, C. Y., Patrudu, M., Baxter, S. A., Tapia, M. A., Darnell, J., Prevette, K., Gibson, A. G., Ayoku, S. A., Campbell, L., Coffield, J. W., Keyser, B. M., Ganesh, B. S., Gale, N. and Jordan, K. G. (2025). Randomized crossover clinical studies to assess abuse liability and nicotine pharmacokinetics of Velo Oral Nicotine pouches. Front Pharmacol, 1547073. Available from: https://www.ncbi.nlm.nih.gov/pubmed/40183092


Yang, J., Guo, Y., Wang, Z., Wang, Y., Fu, D., Liu, Q., Solan, G. A., Ma, Y. and Sun, W. H. (2025). Manganese-Catalyzed Asymmetric Hydrogenation of Pyridyl Cyclic N-Alkyl Imines: A Direct Route to S-Nicotine and Derivatives. Org Lett, 11, 2564-2568. Available from: https://www.ncbi.nlm.nih.gov/pubmed/40070246


Aldeek, F., Wagner, K., Haase, V., Sublette, E. and Lopez, V. (2025). Analysis and Toxicological Evaluation of Nicotine Degradants and Impurities in Oral Tobacco Products: A Case Study of on! PLUS Nicotine Pouches. ACS Omega, 6, 6267-6278. Available from: https://www.ncbi.nlm.nih.gov/pubmed/39989796


Effah, F., Sun, Y., Friedman, A. and Rahman, I. (2025). Emerging nicotine analog 6-methyl nicotine increases reactive oxygen species in aerosols and cytotoxicity in human bronchial epithelial cells. Toxicol Lett, Sep-15. Available from: https://www.ncbi.nlm.nih.gov/pubmed/39894318


Effah, F., Sun, Y., Lin, K. and Rahman, I. (2025). A comparative toxicological evaluation of emerging nicotine analogs 6-methyl nicotine and nicotinamide: a scoping review. Arch Toxicol. Available from: https://www.ncbi.nlm.nih.gov/pubmed/39937258


Sanchez, L. M., Leventhal, A. M., Unger, J. B. and Galimov, A. (2025). Expanding synthetic nicotine commercial market: Aroma King's 'NoNic' pouches and e-cigarettes. Tob Control. Available from: https://www.ncbi.nlm.nih.gov/pubmed/39922702


Giovenco, D. P., Spillane, T. E., Lee, H. M., Ali, N., Little, R. M. P., Rahman, S. N. and Yagoda, S. S. (2025). Retail availability of oral nicotine pouches in 3 US cities: A geographic analysis. Nicotine Tob Res. Available from: https://www.ncbi.nlm.nih.gov/pubmed/39756396


Jabba, S. V., Silinski, P., Yang, A. Y., Ouyang, W. and Jordt, S. E. (2024). Artificial Sweeteners in US-Marketed Oral Nicotine Pouch Products: Correlation with Nicotine Contents and Effects on Product Preference. Nicotine Tob Res. Available from: https://www.ncbi.nlm.nih.gov/pubmed/39656927


Trotsko, N., Miroslaw, B., Jasinski, R., Dlugosz, M., Sadczuk, M. and Demchuk, O. M. (2024). Efficient Method of (S)-Nicotine Synthesis. Molecules, 23. Available from: https://www.ncbi.nlm.nih.gov/pubmed/39683890


Vanhee, C., Dill, M., Canfyn, M., Tuenter, E. and Barhdadi, S. (2024). The Emergence of a Novel Synthetic Nicotine Analog 6-Methyl Nicotine (6-MN) in Proclaimed Tobacco- and Nicotine-Free Pouches Available in Europe. Drug Test Anal. Available from: https://www.ncbi.nlm.nih.gov/pubmed/39697046


Zamarripa, C. A., Dowd, A. N., Elder, H. J., Czaplicki, L., Tfayli, D., Rastogi, K., Thrul, J., Strickland, J. C., Moran, M. B. and Spindle, T. R. (2024). A comprehensive review on oral nicotine pouches: Available scientific evidence and future research needs. Exp Clin Psychopharmacol. Available from: https://www.ncbi.nlm.nih.gov/pubmed/39621395


Earlier news and research

For news items and research on this topic earlier than 2025, click here.

Intro
Chapter 2