{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T22:19:11Z","timestamp":1787869151957,"version":"build-2784847793"},"posted":{"date-parts":[[2026,8,24]]},"group-title":"Pharmacology and Toxicology","reference-count":62,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["U54DA036151"],"award-info":[{"award-number":["U54DA036151"]}],"id":[{"id":"https:\/\/ror.org\/00fq5cm18","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01DA060884"],"award-info":[{"award-number":["R01DA060884"]}],"id":[{"id":"https:\/\/ror.org\/00fq5cm18","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30CA014236"],"award-info":[{"award-number":["P30CA014236"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,27]]},"abstract":"<jats:p>Background: In the United States, several states have restricted sales of flavoured tobacco products, including popular menthol- and mint-flavoured Oral Nicotine Pouches (ONP). In response, tobacco companies introduced \"unflavoured\" ONP containing odorless synthetic cooling agents. Since these, in turn, have become targets of legislative bans, the tobacco industry may seek out flavourants with other sensory effects to increase the appeal of \"unflavoured\" ONP.\nMethods: Online merchants were searched for \"unflavored\" ONP marketed to consumers in jurisdictions with flavour bans. Sensory effects of aqueous extracts from identified \"heat\", \"spicy\" and \"unflavoured\" ONP were analyzed by Ca2+ microfluorimetry in HEK293 cells expressing the human heat\/chili pepper flavourant (capsaicinoid) receptor, hTRPV1. ONP were analyzed for capsaicinoids and sweeteners by Liquid Chromatography\/Mass Spectrometry (LC\/MS).\nResults: A new category of \"heat\" or \"spicy\" ONP was identified, including products marketed as \"unflavoured\". Extracts from all these ONP robustly activated TRPV1, with \"unflavoured\" Lucy Heat the most potent. Chemical analysis demonstrated that Lucy Heat contained the synthetic capsaicinoid nonivamide at high levels (~675 microgram\/pouch), while others contained mixtures of capsaicinoids (5-25 microgram\/pouch) combined with other characterizing flavours (tropical, fruit). All tested ONP contained sweeteners.\nConclusions: The tobacco industry continues to probe regulatory loopholes by claiming that newly introduced capsaicinoid flavourants and sweeteners in ONP do not represent characterizing flavours. This is contradicted by industry and regulatory determinations assigning characterizing flavour properties to these additives. The toxicological health risks of repeated capsaicinoid exposures due to ONP use, in combination with nicotine and other constituents, need to be assessed.<\/jats:p>","DOI":"10.64898\/2026.08.19.745863","type":"posted-content","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T23:30:11Z","timestamp":1787614211000},"source":"Crossref","is-referenced-by-count":0,"title":["Chili Pepper Flavourants in \"Heat\" and \"Unflavoured\" Oral Nicotine Pouches Marketed in the United States"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0646-3519","authenticated-orcid":false,"given":"Sairam V","family":"Jabba","sequence":"first","affiliation":[{"name":"Duke University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9986-6372","authenticated-orcid":false,"given":"Zhong","family":"Li","sequence":"additional","affiliation":[{"name":"Duke University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6171-5622","authenticated-orcid":false,"given":"Sven E","family":"Jordt","sequence":"additional","affiliation":[{"name":"Duke University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026082711051353000_2026.08.19.745863v1.1","unstructured":"NoTobacco(TFI). 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