In vitro evaluation of mutagenic, cytotoxic, genotoxic and oral irritation potential of nicotine pouch products

Miller-Holt, Jacqueline; Abraham, Irene; Sakimura, Masanori; Fukushima, Toshiro; Puglisi, Andrea; Gafner, Jeremie

doi:10.1016/j.toxrep.2022.06.008

Cited by 8 publications

(7 citation statements)

References 13 publications

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“…An in vitro study investigated the oral nicotine pouch products in terms of oral irritation in the EpiGingival™ 3D tissue model and artificial saliva. This study reported oral pouches, as non-genotoxic, and non-cytotoxic, and non-mutagenic [42]. An interesting study by Dawler et al studied the diversity among oral tobacco products and reported the ability of these products to convey a high range of carcinogenic and nicotine, Tobacco-specific nitrosamines (TSNAs) which could be very harmful to the users [43].…”

Section: Application Of Onps In Research Studiesmentioning

confidence: 98%

Classification, Perception, Sociological Aspects, and Toxicity of Emerging Flavored Oral Nicotine Pouches

Shaikh¹,

Newton²,

Tung³

et al. 2023

Preprint

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Introduction: Oral Nicotine Pouches (ONPs) are the new form of nicotine pouches that have become a type of emerging smokeless tobacco product sold by various tobacco companies. These smokeless tobacco products are being marketed for usage all over as Snus containing tobacco-derived nicotine (Natural) or as tobacco-free nicotine (Synthetic) as substitutes for other tobacco products that are limited in public places. ONPs have become popular tobacco products among adolescents/young adults and over 50% of young adult users of ONP use flavored ONP, such as menthol/mint, tobacco, dessert/candy, and fruity, being the most popular flavors. Various new ONP flavors are currently popular locally as well in the online market. Tobacco, Menthol, and fruit-flavored ONPs could motivate cigarette smokers to alteration to ONPs. Methods: We expanded our knowledge on natural/synthetic ONP flavors wheels to available data on ONPs, describing in detail their flavors and brands (US and Europe) in both natural/Synthetic ONP categories. We classified over 152 snus and 228 synthetic ONPs into the following flavor categories: “Tobacco”, “Menthol/Mint”, “Fruity”, “Candy/Deserts”, “Drink”, “Aroma”, “Spices” and “Mixed Flavors”. Results: Based on total numbers, wefound that the most popular ONPs flavor sold as tobacco and menthol to be among natural ONPs, among synthetic ONPs fruity and menthol as the most prominent flavors with varying concentrations of nicotine and other flavoring chemicals including coolant WS-23. We also illustrated possible molecular targets and toxicities due to exposure to ONPs activating several signaling cascades like AKT and NF-B might possibly lead to apoptosis and epithelial mesenchymal transition (EMT). Conclusions: Considering the marketing of ONP products with various flavor profiles and most of these products containing tobacco/menthol/fruit flavor, it is likely to have regulation and marketing disclaimer on some of these products. Further, it would be logical to determine how the market reacts in terms of compliance and non-compliance with flavor restrictions by the regulatory agencies.

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Section: Application Of Onps In Research Studiesmentioning

confidence: 98%

Classification, Perception, Sociological Aspects, and Toxicity of Emerging Flavored Oral Nicotine Pouches

Shaikh¹,

Newton²,

Tung³

et al. 2023

Preprint

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“…Overall, while between-flavour differences were observed, these differences were only assessed relative to negative control, and the statistical significance of the differences between flavours was not evaluated. Moreover, the study did not assess the effects in the assays relative to cigarette smoke, as was performed in other studies [34,38,40], misclassified at least one of the study products, and did not include any pouches containing synthetic nicotine. These methodological issues may prevent firm conclusions from being drawn from the study data.…”

Section: Toxicological Analysis Of Tfnpsmentioning

confidence: 99%

“…In the studies described above, TFNP extracts were generated using tissue culture media or saline. In a slightly different approach, Miller-Holt et al [40] investigated the in vitro toxicological potential of extracts from three variants of "Nordic Spirit" TFNPs, which were generated using complete artificial saliva (CAS). These extracts were compared with CAS extracts from the CORESTA CRP1.1 reference smokeless tobacco (snus) product and smoke condensed from the 1R6F reference cigarette.…”

Section: Toxicological Analysis Of Tfnpsmentioning

confidence: 99%

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Tobacco-Free Nicotine Pouches and Their Potential Contribution to Tobacco Harm Reduction: A Scoping Review

Grandolfo,

Ogden,

Fearon

et al. 2024

Cureus

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Tobacco harm reduction (THR) refers to strategies designed to reduce the health risks associated with tobacco smoking but may involve continued use of nicotine and/or tobacco. Next-generation products (NGPs) are a THR alternative as they do not burn tobacco or produce smoke and deliver nicotine and have fewer and substantially lower levels of harmful chemicals compared to cigarettes. Tobacco-free nicotine pouches (TFNPs) are an emerging category of nicotine-containing oral products that do not combust or contain tobacco leaf. Similar to Swedish snus, TFNPs are placed between a user's lip and gum, and nicotine is absorbed through the oral mucosa rather than being inhaled. The aim of this scoping review was to systematically collate and evaluate published scientific evidence (cut-off of 31 May 2023) identified from bibliometric databases investigating the potential of TFNPs to contribute to THR. Overall, studies examining chemical constituents indicated that the use of TFNPs may result in lower exposure to toxicants than other tobacco or nicotine-containing products, both combustible and non-combustible. This reduction in toxicant exposure has been demonstrated by multiple human biomarker studies and in vitro toxicological assessments to translate to harm reduction potential in smokers switching to TFNPs. However, further study is warranted. At present, there is some evidence from human behavioral research that TFNPs can support either transitioning away from smoking or reducing cigarette consumption. Furthermore, TFNP use appears very much limited to current users of traditional tobacco products, and youth uptake has been limited. In conclusion, the findings of this review indicate that TFNPs have the potential to support THR efforts and may help inform evidence-based regulation.

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“…ONP uptake has thus far primarily occurred among adults and young people who use other forms of tobacco [8][9][10]. Because ONPs have fewer toxicants than other forms of tobacco [11], they might offer an opportunity for harm reduction if tobacco users completely switch to these products [12][13][14][15]. The subjective appeal of ONPs relative to cigarettes is one aspect of their misuse liability that could support switching from cigarettes to ONPs.…”

Section: Introductionmentioning

confidence: 99%

Evaluating the effects of nicotine concentration on the appeal and nicotine delivery of oral nicotine pouches among rural and Appalachian adults who smoke cigarettes: A randomized cross‐over study

Keller‐Hamilton,

Alalwan,

Curran

et al. 2023

Addiction

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Background and aimsOral nicotine pouches (ONPs) probably offer reduced harm compared with cigarettes, but independent data concerning their misuse liability are lacking. We compared nicotine delivery and craving relief from ONPs with different nicotine concentrations to cigarettes.DesignThis was a single‐blind, three‐visit (≥ 48‐hour washout), randomized‐cross‐over study. Participants were encouraged to complete all study visits in less than 1 month.SettingThe study took place in Rural/Appalachian Ohio.ParticipantsParticipants comprised 30 adults who smoke cigarettes. Participants (meanage = 34.5) were 60% men and 90% White.InterventionParticipants who were ≥ 12‐hour tobacco‐abstinent used: (1) a 3‐mg nicotine concentration ONP, (2) a 6‐mg nicotine concentration ONP and (3) usual brand cigarette in separate visits. ONPs (wintergreen Zyn) were used for 30 minutes; cigarettes were puffed every 30 sec for 5 minutes.MeasurementsPlasma nicotine and self‐reported craving were assessed at t = 0, 5, 15, 30, 60 and 90 minutes. The primary outcome was plasma nicotine concentration at t = 30 minutes. A secondary outcome was craving relief at t = 5 minutes.FindingsAt t = 30, mean [95% confidence interval (CI)] plasma nicotine was 9.5 ng/ml (95% CI = 7.1, 11.9 ng/ml) for the 3 mg nicotine ONP, 17.5 ng/ml (95% CI = 13.7, 21.3) for the 6 mg nicotine ONP and 11.4 ng/ml (95% CI = 9.2, 13.6 ng/ml) for the cigarette. Mean plasma nicotine at t = 30 minutes differed between the 3‐ and 6‐mg nicotine ONPs (P = 0.001) and between the 6‐mg nicotine ONP and cigarette (P = 0.002). Mean (95% CI) craving at t = 5 minutes was lower for the cigarette (mean = 1.00, 95% CI = 0.61, 1.39) than either the 3 mg (mean = 2.25, 95% CI = 1.68, 2.82; P < 0.0001) or 6 mg nicotine (mean = 2.19, 95% CI = 1.60, 2.79; P < 0.0001) ONP.ConclusionsAmong adult smokers, using 6‐mg nicotine concentration oral nicotine pouches (ONPs) was associated with greater plasma nicotine delivery at 30 minutes than 3‐mg ONPs or cigarettes, but neither ONP relieved craving symptoms at 5 minutes as strongly as a cigarette. Accelerating the speed of nicotine delivery in ONPs might increase their misuse liability relative to cigarettes.

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In vitro evaluation of mutagenic, cytotoxic, genotoxic and oral irritation potential of nicotine pouch products

Cited by 8 publications

References 13 publications

Classification, Perception, Sociological Aspects, and Toxicity of Emerging Flavored Oral Nicotine Pouches

Classification, Perception, Sociological Aspects, and Toxicity of Emerging Flavored Oral Nicotine Pouches

Tobacco-Free Nicotine Pouches and Their Potential Contribution to Tobacco Harm Reduction: A Scoping Review

Evaluating the effects of nicotine concentration on the appeal and nicotine delivery of oral nicotine pouches among rural and Appalachian adults who smoke cigarettes: A randomized cross‐over study

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