Published: 2022-10-26

Emissions, puffing topography, mouth level exposure and consumption among Japanese users of tobacco heated products

Krishna Prasad, Adam Gray, Lauren Edward, Carol Goss


Background: Tobacco heating products (THPs), which heat rather than burn tobacco, have been demonstrated by a number of studies to produce an aerosol with substantially lower levels of toxicants and reduced cytotoxicity relative to cigarette smoke. As they evolve in design and function, however, it is important to verify that variant THPs maintain sufficient equivalence to the original product if we are to leverage existing foundational datasets. Recent studies suggest that a bridging approach, in which a variant is shown to be comparable to the original product on which a large foundational dataset has been generated, might be used to ensure that the same product-related claims apply.

Methods: In this study, emissions and consumer behaviour were assessed for two variants of gloTM THPs: an extensively tested gloTM type 1 (glo 2.0), and gloTM type 3 (glo hyper) in base and boost modes. Emissions testing was conducted by measuring the percentage reduction of TobReg9 toxicants, relative to a 1R6F reference cigarette.

Results: Consumer behaviour, including puffing topography, average daily consumption (ADC) and mouth level exposure (MLE) to NFDPM and nicotine was measured among 63 regular gloTM users in Tokyo, Japan. Emissions testing showed a substantial reduction in TobReg9 toxicants compared to the reference cigarette (95.5-97.3%), whilst there were no substantial differences in the ADC, puffing behaviour or MLE among the three THPs.

Conclusions: Emissions analysis based on TobReg9 toxicants and consumer behaviour data provide evidence that the gloTM type 3 is comparable to gloTM type 1, indicating the possibility of using a bridging approach for the analysis of variant THPs based on use behaviour alone.


THPs, gloTM, User behaviour, Puffing topography, ADC, MLE, Emissions, Bridging

Full Text:



WHO report on the global tobacco epidemic, 2011: Warning about the dangers of tobacco. Geneva: World Health Organization (2011). Available at: Accessed on 3 June 2022.

Proctor C. Assessment of tobacco heating product THP1.0. Part 1: Series introduction. Regul Toxicol Pharmacol. 2018;93:1-3.

Public Health England. Evidence reviews of e-cigarettes and heated tobacco products 2018. A report commissioned by Public Health England. London: Public Health England. 2018.

Forster M, Fiebelkorn S, Yurteri C, Mariner D, Liu C, Wright C, et al. Assessment of novel tobacco heating product THP1.0. Part 3: Comprehensive chemical characterization of harmful and potentially harmful aerosol emissions. Regul Toxicol Pharmacol. 2018;93:14-33.

Savareear B, Escobar-Arnanz J, Brokl M, Saxton MJ, Wright C, Liu C, et al. Comprehensive comparative compositional study of the vapour phase of cigarette mainstream tobacco smoke and tobacco heating product aerosol. J Chromatogr A. 2018;1581-1582:105-15.

Kopa PN, Pawliczak R. IQOS-a heat-not-burn (HnB) tobacco product – chemical composition and possible impact on oxidative stress and inflammatory response. A systematic review. Toxicol Mech Methods. 2020;30(2):81-7.

Kärkelä T, Tapper U, Kajolinna T. Comparison of 3R4F cigarette smoke and IQOS heated tobacco product aerosol emissions. Environ Sci Pollut Res Int. 2022;29(18):27051-69.

Jaunky T, Adamson J, Santopietro S, Terry A, Thorne D, Breheny D, et al. Assessment of tobacco heating product THP1.0. Part 5: In vitro dosimetric and cytotoxic assessment. Regul Toxicol Pharmacol. 2018;93:52-61.

Dusautoir R, Zarcone G, Verriele M, Garçon G, Fronval I, Beauval N, et al. Comparison of the chemical composition of aerosols from heated tobacco products, electronic cigarettes and tobacco cigarettes and their toxic impacts on the human bronchial epithelial BEAS-2B cells. J Hazard Mater. 2021;401:123417.

Heide J, Adam TW, Jacobs E, Wolter JM, Ehlert S, Walte A, et al. Puff-Resolved Analysis and Selected Quantification of Chemicals in the Gas Phase of E-Cigarettes, Heat-Not-Burn Devices, and Conventional Cigarettes Using Single-Photon Ionization Time-of-Flight Mass Spectrometry (SPI-TOFMS): A Comparative Study. Nicotine Tob Res. 2021;23(12):2135-44.

McEwan M, Gale N, Ebajemito JK, Camacho OM, Hardie G, Proctor CJ, et al. A randomized controlled study in healthy participants to explore the exposure continuum when smokers switch to a tobacco heating product or an E-cigarette relative to cessation. Toxicol Rep. 2021;8:994-1001.

Gale N, McEwan M, Camacho OM. Changes in biomarkers after 180 days of tobacco heating product use: a randomised trial. Intern Emerg Med. 2021;16:2201-12.

Polosa R, Morjaria JB, Prosperini U, Busà B, Pennisi A, Gussoni G, et al. Health outcomes in COPD smokers using heated tobacco products: a 3-year follow-up. Intern Emerg Med. 2021;16(3):687-96.

Murphy J, Gaca M, Lowe F, Minet E, Breheny D, Prasad K et al. Assessing modified risk tobacco and nicotine products: Description of the scientific framework and assessment of a closed modular electronic cigarette. Regul Toxicol Pharmacol. 2017;90:342-57.

Berman ML, Connolly G, Cummings MK, Djordjevic MV, Hatsukami DK, Henningfield JE, et al. Providing a science base for the evaluation of tobacco products. Tob Regul Sci. 2015;1:76e93.

Smith MR, Clark B, Lüdicke F, Schaller JP, Vanscheeuwijck P, Hoeng J. Evaluation of the Tobacco Heating System 2.2. Part 1: description of the system and the scientific assessment program. Regul Toxicol Pharmacol. 2016;81:S17eS26

Goodall S, Gale N, Thorne D, Hadley S, Prasad K, Gilmour I, et al. Evaluation of behavioural, chemical, toxicological and clinical studies of a tobacco heated product gloTM and the potential for bridging from a foundational dataset to new product iterations. Toxicology Rep. 2022;14.

Gaca M, Williamson J, Digard H, Adams L, Hawkridge L, Proctor C. Bridging: Accelerating Regulatory Acceptance of Reduced-Risk Tobacco and Nicotine Products. Nicotine Tob Res. 2022;41.

Midha KK, McKay G. Bioequivalence; its history, practice, and future. AAPS J. 2009;11(4):664-70.

Schlage WK, Titz B, Iskandar A, Poussin C, Van der Toorn M, Wong ET, et al. Comparing the preclinical risk profile of inhalable candidate and potential candidate modified risk tobacco products: A bridging use case. Toxicol Rep. 2020;7:1187-206.

Jaunky T, Thorne D, Baxter A, Hadley S, Frosina J, Breheny D, et al. An Experimental Analytical and In Vitro Approach to Bridge Between Different Heated Tobacco Product Variants. Contributions Tobacco Nicotine Res. 2022;31(1):1-9.

Gee J, Prasad K, Slayford S, Gray A, Nother K, Cunningham A, et al. Assessment of tobacco heating product THP1.0. Part 8: Study to determine puffing topography, mouth level exposure and consumption among Japanese users. Regul Toxicol Pharmacol. 2018;93:84-91.

Jones J, Slayford S, Gray A, Brick K, Prasad K, Proctor C. A cross-category puffing topography, mouth level exposure and consumption study among Italian users of tobacco and nicotine products. Sci Rep. 2020;10(1):12.

Burns DM, Dybing E, Gray N, Hecht S, Anderson C, Sanner T, et al. Mandated lowering of toxicants in cigarette smoke: a description of the World Health Organization TobReg proposal. Tob Control. 2008;17(2):132-41.

ISO. Tobacco and tobacco products-Atmosphere for conditioning and testing, ISO3402:1999 (International Organization for Standardization, 1999). ISO. Tobacco and tobacco products-Atmosphere for conditioning and testing, ISO3402:1999 (International Organization for Standardization. 1999.

ISO. ISO and Health Canada intense smoking parameters-Part 1: Results of an international machine smoking study. ISO/TR19478-1:2014 (International Organization for Standardization. 2014.

International Chamber of Commerce (ICC)/ESOMAR, 2016. International code on market, opinion and social research and data analytics. Available at: http://ckqtawvjq00uuk dtrhst5sk9u-iccesomar-international-code-english.pdf. Accessed on 5 June 2022).

Slayford S, Frost B. A device to measure a smokers’ puffing topography and real-time puff by puff “tar” delivery. Beit Tab Int. 2014;26(18):74-84.

Cunningham A, Slayford S, Vas C, Gee J, Costigan S, Prasad K. Development, validation and application of a device to measure e-cigarette users' puffing topography. Sci Rep. 2016;6:35071.

Hukkanen J, Jacob P III, Benowitz NL. Metabolism and disposition kinetics of nicotine. Pharmacol Rev. 2005;57(1):79-115.

Piller M, Gilch G, Scherer G, Scherer M. Simple, fast and sensitive LC-MS/MS analysis for the simultaneous quantification of nicotine and 10 of its major metabolites. J Chromatogr B Analyt Technol Biomed Life Sci. 2014;951-952:7-15.

Wang L, Bernert JT, Benowitz NL. Collaborative method performance study of the measurement of nicotine, its metabolites, and total nicotine equivalents in human urine. Cancer Epidemiol Biomarkers Prev. 2018;27(9):1083-90.

Benowitz NL, St. Helen G, Nardone N, Cox LS, Jacob P III. Urine Metabolites for Estimating Daily Intake of Nicotine from Cigarette Smoking. Nicotine Tobacco Res. 2020;288-92

Eaton D, Jakaj B, Forster M, Nicol J, Mavropoulou E, Scott K, et al. Assessment of tobacco heating product THP1.0. Part 2: product design, operation and thermophysical characterisation, Regul. Toxicol Pharmacol. 2018;93:4-13.