Our 9-step scientific Risk Assessment Framework allows us to understand:
Through our published science, we can summarise the following key conclusions for each of our Smokeless Products: glo, Vuse and Velo.
Table 1. A summary of conclusions for our Smokeless Products from key scientific studies within our risk assessment framework.
Heated Products
-glo-
Vapour Products
-Vuse-
Oral Nicotine Pouches
-Velo-
Combustion studies
(see Pages 172-177)
No Combustion
Our glo products heat their consumables below 300°C, and our science has shown combustion does not occur below 300°C.
No Combustion
Our Vuse products heat its e-liquid below 200°C delivering an aerosol without combustion
No Combustion
Our Velo products are oral products that are consumed without heat.
Emissions studies
(see Pages 172-177)
90-95%
less toxicants*† ^\
>99%
less toxicants*† ^
>99%
less toxicants*† ^
Toxicology studies
(see Pages 172-177)
98%
lower genotoxic response#
90%
lower cytotoxic response#
95%
less cell stress#
>99%
lower genotoxic response#
95%
lower cytotoxic response#
>98%
less cell stress#
>99%
lower genotoxic response#
99%
lower cytotoxic response#
>98%
less cell stress#
Clinical: Exposure
(see Pages 184-189)
Statistically Significant
Reductions in Exposure
Complete switching to glo can reduce a smoker's exposure to several harmful chemicals as compared to continued smoking.
Statistically Significant
Reductions in Exposure
Adult solus consumers of our Vuse products have lower levels of exposure to several harmful chemicals compared to adult smokers.
Statistically Significant
Reductions in Exposure
Adult solus consumers of our Velo products have lower levels of exposure to several harmful chemicals compared to adult smokers.
Clinical: Individual Risk
(see Pages 190-193)
Favourable Changes in Biomarkers of Potential Harm
Complete switching to glo
from combustible cigarettes can result in favourable changes in biomarkers of potential harm.
Favourable Differences in Biomarkers of Potential Harm
Adult solus consumers of our Vuse products have shown favourable differences in biomarkers of potential harm as compared to smokers.
Favourable Differences in Biomarkers of Potential Harm
Adult solus consumers of our Velo products have shown favourable differences in biomarkers of potential harm as compared to smokers.
Beyond our own science, there is evidence across both scientific organisations/institutes and industry that supports a scientific risk assessment framework approach with published data available (Table 2). Scientific organisations including the National Academy of Sciences, Engineering and Medicine (NASEM),[1] Institute of Medicine (IOM),[2] U.S. Food and Drug Administration (FDA),[3,4] and Tobacco Product Assessment Consortium (TobPRAC)[5], all layout frameworks as how to evaluate the risk profile of Smokeless Products.
"Evidence-based tobacco regulation requires a comprehensive scientific framework to guide the evaluation of new tobacco products and health-related claims made by product manufacturers."
TobPRAC[5]
Table 2. Selection of Third parties' scientific publications in areas described by the 9-step scientific Risk Assessment Framework**
Heated Products
Vapour Products
Oral Nicotine Pouches
Combustion Studies
Academia, China[6]
Philip Morris International[7]
Emission Studies
Regulator, Japan[8]
Philip Morris International[9, 10]
Philip Morris International[11]
Altria[12, 13]
Imperial Brands[14]
Regulator, Germany[15]
Altria[16]
Toxicological Studies
Academia, Italy[17]
Philip Morris International[18, 19]
Japan Tobacco International[20, 21]
Imperial Brands[22, 23, 24]
Academia, Italy[17]
Philip Morris International[25]
Altria[26, 27]
Altria/
Philip Morris International[28]
Imperial Brands[17, 29]
Japan Tobacco International[30]
Imperial Brands[31]
Use Behaviour
Philip Morris International[32]
Altria[33]
Altria[34, 35]
Imperial Brands[36]
Altria[37, 38]
Clinical: Pharmacokinetic Studies
Philip Morris International[39, 40]
Imperial Brands[41]
Imperial Brands[42]
Academia, U.S.[43]
Altria[44, 45]
Imperial Brands[46]
Swedish Match[47]
Clinical: Exposure
Philip Morris International[48, 49, 50]
Japan Tobacco International[51, 52]
Academia & Regulator, U.K. and U.S.[53]
Academia & Regulator, U.S[54]
Altria[55, 56]
Imperial Brands[57, 58]
Altria[59]
Clinical: Individual Risk
Philip Morris International[34, 36]
Altria[39, 40, 59]
Population Risk Post-Market Surveillance
Philip Morris International[60]
Japan Tobacco International[61]
Altria[43]
Academia, U.S.[62]
Epidemiological Modelling Data
Philip Morris International[63, 64]
Japan Tobacco International[65]
Altria[66]
Footnotes
* Based on the weight of evidence and assuming a complete switch from cigarette smoking. These products are not risk free and are addictive.
† Our Vapour product Vuse (including Alto, Solo, Ciro and Vibe), and certain products, including Velo, Grizzly, Kodiak, and Camel Snus, which are sold in the U.S., are subject to FDA regulation and no reduced-risk claims will be made as to these products without agency clearance.
^ On average, in comparison with smoke from a scientific standard reference cigarette (approximately 9 mg tar).
# On average, in comparison with smoke from a scientific standard reference cigarette (approximately 9 mg tar)
** The allocation for illustrative purposes of the individual third parties’ scientific publications does not necessarily mean that the third parties listed follow a similar 9 step framework approach in their science.
References
[1] Institute of Medicine Staff, Clearing the smoke: assessing the science base for tobacco harm reduction. National Academies Press, 2001. Available at: http://nap.nationalacademies.org/10029
[2] Institute of Medicine, Scientific Standards for Studies on Modified Risk Tobacco Products. Washington, DC: The National Academies Press, 2012. DOI: 10.17226/13294
[3] U.S. Food & Drug Administration, Premarket Tobacco Product Applications. Available at: https://www.fda.gov/tobacco-products/market-anddistribute-tobacco-product/premarket-tobacco-product-applications (Accessed: 26 July 2024)
[4] U.S. Food & Drug Administration, Modified Risk Tobacco Products. Available at: https://www.fda.gov/tobacco-products/advertising-andpromotion/modified-risk-tobacco-products (Accessed: 2 July 2024)
[5] Berman, M. L., et al., Providing a science base for the evaluation of tobacco products. Tob. Regul Sci, 2015. 1(1): p.76. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4671507/
[6] Li, X., et al., Chemical analysis and simulated pyrolysis of tobacco heating system 2.2 compared to conventional cigarettes. Nicotine Tob Res, 2019. 21(1): p. 111-118. DOI: 10.1093/ntr/nty005
[7] Cozzani, V., et al., An experimental investigation into the operation of an electrically heated tobacco system. Thermochim Acta, 2020. 684:178475. DOI: 10.1016/j.tca.2019.178475
[8] Bekki, K., et al., Comparison of chemicals in mainstream smoke in heat-not-burn tobacco and combustion cigarettes. J UOEH, 2017. 39(3): p. 201-207. DOI: 10.7888/juoeh.39.201
[9] Bentley, M. C., et al., Comprehensive chemical characterization of the aerosol generated by a heated tobacco product by untargeted screening. Anal Bioanal Chem, 2020. 412: p. 2675-2685. DOI: 10.1007/s00216-020-02502-1
[10] Jaccard, G., et al., Comparative assessment of HPHC yields in the Tobacco Heating System THS2. 2 and commercial cigarettes. Regul Toxicol Pharmacol, 2017. 90: p. 1-8. DOI: 10.1016/j.yrtph.2017.08.006
[11] Frege, C., et al., Assessment of single-photon ionization mass spectrometry for online monitoring of in vitro aerosol exposure experiments. Chem Res Toxicol, 2020. 33(2): p. 505-514. DOI: 10.1021/acs.chemrestox.9b00381
[12] Shah, N.H., et al., Non-targeted analysis using gas chromatography-mass spectrometry for evaluation of chemical composition of E-vapor products. Front Chem, 2021. 9:742854. DOI: 10.3389/fchem.2021.742854
[13] Wagner, K.A., et al., An evaluation of electronic cigarette formulations and aerosols for harmful and potentially harmful constituents (HPHCs) typically derived from combustion. Regul Toxicol Pharmacol, 2018. 95: p. 153-160. DOI: 10.1016/j.yrtph.2018.03.012
[14] Rudd, K., et al., Chemical composition and in vitro toxicity profile of a pod-based e-cigarette aerosol compared to cigarette smoke. Appl In Vitro Toxicol, 2020. 6(1): p. 11-41. DOI: 10.1089/aivt.2019.0015
[15] Mallock, N., et al., Levels of nicotine and tobacco-specific nitrosamines in oral nicotine pouches. Tob Control, 2024. 33(2): p. 193-199. DOI: 10.1136/tc-2022-057280
[16] Aldeek, F., et al., Dissolution testing of nicotine release from OTDN pouches: product characterization and product-to-product comparison. Separations, 2021. 8(1):7. DOI: 10.3390/separations8010007
[17] Caruso, M., et al., Screening of different cytotoxicity methods for the assessment of ENDS toxicity relative to tobacco cigarettes. Regul Toxicol Pharmacol, 2021. 125:105018. DOI: 10.1016/j.yrtph.2021.105018
[18] Wong, E.T., et al., Reduced chronic toxicity and carcinogenicity in A/J mice in response to life-time exposure to aerosol from a heated tobacco product compared with cigarette smoke. Toxicol Sci, 2020. 178(1): p. 44-70. DOI: 10.1093/toxsci/kfaa131
[19] Schaller, J.P., et al., Evaluation of the Tobacco Heating System 2.2. Part 2: Chemical composition, genotoxicity, cytotoxicity, and physical properties of the aerosol. Regul Toxicol Pharmacol, 2016. 81(2): p. S27-S47. DOI: 10.1016/j.yrtph.2016.10.001
[20] Ohashi, K., et al., RNA sequencing analysis of early-stage atherosclerosis in vascular-on-a-chip and its application for comparing combustible cigarettes with heated tobacco products. Curr Res Toxicol, 2024. 6:100163. DOI: 10.1016/j.crtox.2024.100163
[21] Muratani, S., et al., Oxidative stress-mediated epidermal growth factor receptor activation by cigarette smoke or heated tobacco aerosol in human primary bronchial epithelial cells from multiple donors. J Appl Toxicol, 2023. 43(9): p. 1347-1357. DOI: 10.1002/jat.4469
[22] Simms, L., et al., Use of a rapid human primary cell-based disease screening model, to compare next generation products to combustible cigarettes. Curr Res Toxicol, 2021. 2: p. 309-321. DOI: 10.1016/j.crtox.2021.08.003
[23] Chapman, F., et al., Twenty-eight day repeated exposure of human 3D bronchial epithelial model to heated tobacco aerosols indicates decreased toxicological responses compared to cigarette smoke. Front Toxicol, 2023. 5:1076752. DOI: 10.3389/ftox.2023.1076752
[24] Chapman, F., et al., Multiple endpoint in vitro toxicity assessment of a prototype heated tobacco product indicates substantially reduced effects compared to those of combustible cigarette. Toxicol In Vitro, 2023. 86:105510. DOI: 10.1016/j.tiv.2022.105510
[25] Giralt, A., et al., Comparison of the biological impact of aerosol of e-vapor device with MESH. technology and cigarette smoke on human bronchial and alveolar cultures. Toxicol Lett, 2021. 337: p. 98-110. DOI: 10.1016/j.toxlet.2020.11.006
[26] Wong, E.T., et al., Assessment of inhalation toxicity of cigarette smoke and aerosols from flavor mixtures: 5-week study in A/J mice. J Appl Toxicol, 2022. 42(10): p. 1701-1722. DOI: 10.1002/jat.4338
[27] Wong, E.T., et al., A 6-month inhalation toxicology study in Apoe−/− mice demonstrates substantially lower effects of e-vapor aerosol compared with cigarette smoke in the respiratory tract. Arch Toxicol, 2021. 95: p. 1805-1829. DOI: 10.1007/s00204-021-03020-4
[28] Iskandar, A.R., et al., A lower impact of an acute exposure to electronic cigarette aerosols than to cigarette smoke in human organotypic buccal and small airway cultures was demonstrated using systems toxicology assessment. Intern Emerg Med, 2019. 14: p. 863-883. DOI: 10.1007/s11739-019-02055-x
[29] Simms, L., et al., Use of human induced pluripotent stem cell-derived cardiomyocytes to predict the cardiotoxicity potential of next generation nicotine products. Front Toxicol, 2022. 4:747508. DOI: 10.3389/ftox.2022.747508
[30] Miller-Holt, J., et al., In vitro evaluation of mutagenic, cytotoxic, genotoxic and oral irritation potential of nicotine pouch products. Toxicol Rep, 2022. 9: p. 1316-1324. DOI: 10.1016/j.toxrep.2022.06.008
[31] Yu, F., et al., Preclinical assessment of tobacco-free nicotine pouches demonstrates reduced in vitro toxicity compared with tobacco snus and combustible cigarette smoke. Appl In Vitro Toxicol, 2022. 8(1): p. 24-35. DOI: 10.1089/aivt.2021.0020
[32] Roulet, S., et al., Potential predictors of adoption of the Tobacco Heating System by US adult smokers: An actual use study. F1000Res, 2019. 8: 214 DOI: 10.12688/f1000research.17606.2
[33] Noggle, B., et al., A reduced exposure heated tobacco product was introduced then abruptly taken off United States shelves: results from a tobacco harm reduction natural experiment. Harm Reduct J, 2024. 21: 84. DOI: 10.1186/s12954-024-01000-2
[34] McCaffrey, S.A., et al., Development and validation of behavioral intention measures of an E-vapor product: intention to try, use, dual use, and switch. Health Qual Life Outcomes, 2021. 19:123. DOI: 10.1186/s12955-021-01764-2
[35] Vansickel, A.R., et al., Characterization of puff topography of a prototype electronic cigarette in adult exclusive cigarette smokers and adult exclusive electronic cigarette users. Regul Toxicol Pharmacol, 2018. 98: p. 250-256. DOI: 10.1016/j.yrtph.2018.07.019
[36] Fearon, I.M., et al., Curiosity and intentions to use myblu e-cigarettes and an examination of the ‘gateway’theory: Data from cross-sectional nationally representative surveys. Drug Test Anal, 2023. 15(10): p. 1257-1269. DOI: 10.1002/dta.3450
[37] Cheng, H.G., et al., Effect of Flavored on! Nicotine Pouch Products on Smoking Behaviors: Protocol for a Sequential, Multiple Assignment, Randomized Controlled Trial. JMIR Res Protoc, 2024. 13(1): e56565. DOI: 10.2196/56565
[38] Becker, E., et al., Characterization of Ad Libitum use behavior of On! Nicotine pouches. Am J Health Behav, 2023. 47(3): p. 428-449. DOI: 10.5993/AJHB.47.3.1
[39] Picavet, P., et al., Comparison of the pharmacokinetics of nicotine following single and ad libitum use of a tobacco heating system or combustible cigarettes. Nicotine Tob Res, 2016. 18(5): p. 557-563. DOI: 10.1093/ntr/ntv220
[40] Brossard, P., et al., Nicotine pharmacokinetic profiles of the Tobacco Heating System 2.2, cigarettes and nicotine gum in Japanese smokers. Regul Toxicol Pharmacol, 2017. 89: p. 193-199. DOI: 10.1016/j.yrtph.2017.07.032
[41] O’Connell, G., et al., A randomised, open-label, cross-over clinical study to evaluate the pharmacokinetic profiles of cigarettes and e-cigarettes with nicotine salt formulations in US adult smokers. Intern Emerg Med, 2019. 14: p .853-861. DOI: 10.1007/s11739-019-02025-3
[42] Keller-Hamilton, B., et al., 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. Addic, 2024. 119(3): p. 464-475. DOI: 10.1111/add.16355
[43] Liu, J., et al., Nicotine pharmacokinetics and subjective responses after using nicotine pouches with different nicotine levels compared to combustible cigarettes and moist smokeless tobacco in adult tobacco users. Psychopharmacol, 2022. 239: p. 2863-2873. DOI: 10.1007/s00213-022-06172-y
[44] Rensch, J., et al., Nicotine pharmacokinetics and subjective response among adult smokers using different flavors of on!. nicotine pouches compared to combustible cigarettes. Psychopharmacol, 2021. 238: p. 3325-3334. DOI: 10.1007/s00213-021-05948-y
[45] Chapman, F., et al., A randomised, open-label, cross-over clinical study to evaluate the pharmacokinetic, pharmacodynamic and safety and tolerability profiles of tobacco-free oral nicotine pouches relative to cigarettes. Psychopharmacol, 2022. 239: p. 2931-2943. DOI: 10.1007/s00213-022-06178-6
[46] Lunell, E., et al., Pharmacokinetic comparison of a novel non-tobacco-based nicotine pouch (ZYN) with conventional, tobacco-based Swedish snus and American moist snuff. Nicotine Tob Res, 2020. 22(10): p. 1757-1763. DOI: 10.1093/ntr/ntaa068
[47] Ansari, S.M., et al., Impact of Switching from Cigarette Smoking to Tobacco Heating System Use on Biomarkers of Potential Harm in a Randomized Trial. Biomark, 2024. 29(5): p. 298-314 DOI: 10.1080/1354750X.2024.2358318
[48] Lüdicke, F., et al., Reduced exposure to harmful and potentially harmful smoke constituents with the tobacco heating system 2.1. Nicotine Tob Res, 2017. 19(2): p. 168-175. DOI: 10.1093/ntr/ntw164
[49] Haziza, C., et al., Reduction in exposure to selected harmful and potentially harmful constituents approaching those observed upon smoking abstinence in smokers switching to the menthol tobacco heating system 2.2 for 3 months (Part 1). Nicotine Tob Res, 2020. 22(4): p. 539-548. DOI: 10.1093/ntr/ntz013
[50] Nishihara, D., et al., A Randomized Control Study in Healthy Adult Smokers to Assess Reduced Exposure to Selected Cigarette Smoke Constituents in Switching to the Novel Heated Tobacco Product DT3.0a. Clin Pharmacol Drug Dev, 2024. 13(1): p. 45-57. DOI: 10.1002/cpdd.1322
[51] Yuki, D., et al., Assessment of the exposure to selected smoke constituents in adult smokers using in-market heated tobacco products: a randomized, controlled study. Sci Rep, 2022. 12: 18167. DOI: 10.1038/s41598-022-22997-1
[52] Shahab, L., et al., Nicotine, carcinogen, and toxin exposure in long-term e-cigarette and nicotine replacement therapy users: a cross-sectional study. Annal Intern Med, 2017. 166(6): p. 390-400. DOI: 10.7326/m16-1107
[53] Goniewicz, M.L., et al., Comparison of nicotine and toxicant exposure in users of electronic cigarettes and combustible cigarettes. JAMA Netw Open, 2018. 1(8):e185937. DOI: 10.1001/jamanetworkopen.2018.5937
[54] Edmiston, J.S., et al., Biomarkers of exposure and biomarkers of potential harm in adult smokers who switch to e-vapor products relative to cigarette smoking in a 24-week, randomized, clinical trial. Nicotine Tob Res, 2022. 24(7): p. 1047-1054. DOI: 10.1093/ntr/ntac029
[55] Oliveri, D., et al., Real-world evidence of differences in biomarkers of exposure to select harmful and potentially harmful constituents and biomarkers of potential harm between adult E-vapor users and adult cigarette smokers. Nicotine Tob Res, 2020. 22(7): p. 1114-1122. DOI: 10.1093/ntr/ntz185
[56] Morris, P., et al., Reductions in biomarkers of exposure to selected harmful and potentially harmful constituents following exclusive and partial switching from combustible cigarettes to my blu™ electronic nicotine delivery systems (ENDS). Intern Emerg Med, 2022. 17(2): p. 397-410. DOI: 10.1007/s11739-021-02813-w
[57] O’Connell, G., et al., Reductions in biomarkers of exposure (BoE) to harmful or potentially harmful constituents (HPHCs) following partial or complete substitution of cigarettes with electronic cigarettes in adult smokers. Toxicol Mech Methods, 2016. 26(6): p. 453-464. DOI: 10.1080/15376516.2016.1196282
[58] Rensch, J., et al., A randomized, controlled study to assess changes in biomarkers of exposures among adults who smoke that switch to oral nicotine pouch products relative to continuing smoking or stopping all tobacco use. J Clin Pharmacol, 2023. 63(10): p. 1108-1118. DOI: 10.1002/jcph.2293
[59] Lizhnyak, P.N., et al., Understanding heterogeneity among individuals who smoke cigarettes and vape: assessment of biomarkers of exposure and potential harm among subpopulations from the PATH Wave 1 Data. Harm Reduct J, 2022. 19(1):90. DOI: 10.1186/s12954-022-00673-x
[60] Sponsiello-Wang, Z., et al., Household surveys in the general population and web-based surveys in IQOS users registered at the Philip Morris International IQOS user database: protocols on the use of tobacco-and nicotine-containing products in Germany, Italy, and the United Kingdom (Greater London), 2018-2020. JMIR Res Protoc, 2019. 8(5):e12061. DOI: 10.2196/12061
[61] Sakaguchi, C., et al., Differences in levels of biomarkers of potential harm among users of a heat-not-burn tobacco product, cigarette smokers, and never-smokers in Japan: a post-marketing observational study. Nicotine Tob Res, 2021. 23(7): p. 1143-1152. DOI: 10.1093/ntr/ntab014
[62] Sparrock, L.S., et al., Nicotine pouch: awareness, beliefs, use, and susceptibility among current tobacco users in the United States, 2021. Int J Environ Res Public Health, 2023. 20(3):2050. DOI: 10.3390/ijerph20032050
[63] Djurdjevic, S., et al., Modeling the population health impact of introducing a modified risk tobacco product into the US market. Healthc, 2018. 6(2): p. 47. DOI: 10.3390/healthcare6020047
[64] Djurdjevic, S., et al., Modeling the impact of changes in tobacco use on individual disease risks. Regul Toxicol Pharmacol, 2018. 97: p. 88-97. DOI: 10.1016/j.yrtph.2018.06.001
[65] Poland, B., and Teischinger, F., Population modelling of modified risk tobacco products accounting for smoking reduction and gradual transitions of relative risk. Nicotine Tob Res, 2017. 19(11): p. 1277-1283. DOI: 10.1093/ntr/ntx070
[66] Wei, L., et al., The impact of cigarette and e-cigarette use history on transition patterns: a longitudinal analysis of the population assessment of tobacco and health (PATH) study, 2013–2015. Harm Reduct J, 2020. 17: 45. DOI: 10.1186/s12954-020-00386-z