Robustness of HPHC Reduction in THS 2.2 Aerosol Relative to 3R4F Reference Cigarette Smoke under Extreme Climatic Conditions

1 Bentley, M. and S. Maeder: Quantification of HPHCs in ENDP Aerosols; in Toxicological Evaluation of Electronic Nicotine Delivery Products. Chapter 4; edited by M.C. Peitsch and J. Hoeng, Academic Press, Cambridge, Massachusetts, USA, 2021, pp 41–81. DOI: 10.1016/B978-0-12-820490-0.00004-3 BentleyM. MaederS. Quantification of HPHCs in ENDP Aerosols in Toxicological Evaluation of Electronic Nicotine Delivery Products. Chapter 4 edited by PeitschM.C. HoengJ. Academic Press Cambridge, Massachusetts, USA 2021 41 81 10.1016/B978-0-12-820490-0.00004-3 Open DOISearch in Google Scholar

2 Boué, S., W.K. Schlage, D. Page, J. Hoeng, and M.C. Peitsch: Toxicological Assessment of Tobacco Heating System 2.2: Findings from an Independent Peer Review; Regul. Toxicol. Pharmacol. 104 (2019) 115–127. DOI: 10.1016/j.yrtph.2019.03.007 BouéS. SchlageW.K. PageD. HoengJ. PeitschM.C. Toxicological Assessment of Tobacco Heating System 2.2: Findings from an Independent Peer Review Regul. Toxicol. Pharmacol. 104 2019 115 127 10.1016/j.yrtph.2019.03.00730878573 Open DOISearch in Google Scholar

3 Kogel, U., B. Titz, W.K. Schlage, C. Nury, F. Martin, A. Oviedo, S. Lebrun, A. Elamin, E. Guedj, K. Trivedi, N.V. Ivanov, P. Vanscheeuwijck, M.C. Peitsch, and J. Hoeng: Evaluation of the Tobacco Heating System 2.2. Part 7: Systems Toxicological Assessment of a Mentholated Version Revealed Reduced Cellular and Molecular Exposure Effects Compared with Mentholated and Non-Mentholated Cigarette Smoke; Regul. Toxicol. Pharmacol. 81 Suppl. 2 (2016) S123–S138. DOI: 10.1016/j.yrtph.2016.11.001 KogelU. TitzB. SchlageW.K. NuryC. MartinF. OviedoA. LebrunS. ElaminA. GuedjE. TrivediK. IvanovN.V. VanscheeuwijckP. PeitschM.C. HoengJ. Evaluation of the Tobacco Heating System 2.2. Part 7: Systems Toxicological Assessment of a Mentholated Version Revealed Reduced Cellular and Molecular Exposure Effects Compared with Mentholated and Non-Mentholated Cigarette Smoke Regul. Toxicol. Pharmacol. 81 Suppl. 2 2016 S123 S138 10.1016/j.yrtph.2016.11.00127818347 Open DOISearch in Google Scholar

4 Lüdicke, F., G. Baker, J. Magnette, P. Picavet, and R. Weitkunat: Reduced Exposure to Harmful and Potentially Harmful Smoke Constituents with the Tobacco Heating System 2.1; Nicotine Tob. Res. 19 (2016) 168–175. DOI: 10.1093/ntr/ntw164 LüdickeF. BakerG. MagnetteJ. PicavetP. WeitkunatR. Reduced Exposure to Harmful and Potentially Harmful Smoke Constituents with the Tobacco Heating System 2.1 Nicotine Tob. Res. 19 2016 168 175 10.1093/ntr/ntw164523436427613951 Open DOISearch in Google Scholar

5 Lüdicke, F., C. Haziza, R. Weitkunat, and J. Magnette: Evaluation of Biomarkers of Exposure in Smokers Switching to a Carbon-Heated Tobacco Product: A Controlled, Randomized, Open-Label 5-Day Exposure Study; Nicotine Tob. Res. 18 (2016) 1606–1613. DOI: 10.1093/ntr/ntw022 LüdickeF. HazizaC. WeitkunatR. MagnetteJ. Evaluation of Biomarkers of Exposure in Smokers Switching to a Carbon-Heated Tobacco Product: A Controlled, Randomized, Open-Label 5-Day Exposure Study Nicotine Tob. Res. 18 2016 1606 1613 10.1093/ntr/ntw022490288926817490 Open DOISearch in Google Scholar

6 Lüdicke, F., P. Picavet, G. Baker, C. Haziza, V. Poux, N. Lama, and R. Weitkunat: Effects of Switching to the Tobacco Heating System 2.2 Menthol, Smoking Abstinence, or Continued Cigarette Smoking on Biomarkers of Exposure: A Randomized, Controlled, Open-Label, Multicenter Study in Sequential Confinement and Ambulatory Settings (Part 1); Nicotine Tob. Res. 20 (2017) 161–172. DOI: 10.1093/ntr/ntw287 LüdickeF. PicavetP. BakerG. HazizaC. PouxV. LamaN. WeitkunatR. Effects of Switching to the Tobacco Heating System 2.2 Menthol, Smoking Abstinence, or Continued Cigarette Smoking on Biomarkers of Exposure: A Randomized, Controlled, Open-Label, Multicenter Study in Sequential Confinement and Ambulatory Settings (Part 1) Nicotine Tob. Res. 20 2017 161 172 10.1093/ntr/ntw287589653328177489 Open DOISearch in Google Scholar

7 Martin, F., M. Talikka, N.V. Ivanov, C. Haziza, J. Hoeng, and M.C. Peitsch: Evaluation of the Tobacco Heating System 2.2. Part 9: Application of Systems Pharmacology to Identify Exposure Response Markers in Peripheral Blood of Smokers Switching to THS 2.2; Regul. Toxicol. Pharmacol. 81 Suppl. 2 (2016) S151–S157. DOI: 10.1016/j.yrtph.2016.11.011 MartinF. TalikkaM. IvanovN.V. HazizaC. HoengJ. PeitschM.C. Evaluation of the Tobacco Heating System 2.2. Part 9: Application of Systems Pharmacology to Identify Exposure Response Markers in Peripheral Blood of Smokers Switching to THS 2.2 Regul. Toxicol. Pharmacol. 81 Suppl. 2 2016 S151 S157 10.1016/j.yrtph.2016.11.01127845159 Open DOISearch in Google Scholar

8 Oviedo, A., S. Lebrun, U. Kogel, J. Ho, W.T. Tan, B. Titz, P. Leroy, G. Vuillaume, M. Bera, F. Martin, G. Rodrigo, M. Esposito, R. Dempsey, N.V. Ivanov, J. Hoeng, M.C. Peitsch, and P. Vanscheeuwijck: Evaluation of the Tobacco Heating System 2.2. Part 6: 90-Day OECD 413 Rat Inhalation Study with Systems Toxicology Endpoints Demonstrates Reduced Exposure Effects of a Mentholated Version Compared with Mentholated and Non-Mentholated Cigarette Smoke; Regul. Toxicol. Pharmacol. 81 Suppl. 2 (2016) S93–S122. DOI: 10.1016/j.yrtph.2016.11.004 OviedoA. LebrunS. KogelU. HoJ. TanW.T. TitzB. LeroyP. VuillaumeG. BeraM. MartinF. RodrigoG. EspositoM. DempseyR. IvanovN.V. HoengJ. PeitschM.C. VanscheeuwijckP. Evaluation of the Tobacco Heating System 2.2. Part 6: 90-Day OECD 413 Rat Inhalation Study with Systems Toxicology Endpoints Demonstrates Reduced Exposure Effects of a Mentholated Version Compared with Mentholated and Non-Mentholated Cigarette Smoke Regul. Toxicol. Pharmacol. 81 Suppl. 2 2016 S93 S122 10.1016/j.yrtph.2016.11.00427818348 Open DOISearch in Google Scholar

9 Schaller, J.-P., D. Keller, L. Poget, P. Pratte, E. Kaelin, D. McHugh, G. Cudazzo, D. Smart, A.R. Tricker, L. Gautier, M. Yerly, R. Reis Pires, S. Le Bouhellec, D. Ghosh, I. Hofer, E. Garcia, P. Vanscheeuwijck, and S. Maeder: Evaluation of the Tobacco Heating System 2.2. Part 2: Chemical Composition, Genotoxicity, Cytotoxicity, and Physical Properties of the Aerosol; Regul. Toxicol. Pharmacol. 81 (2016) S27–S47. DOI: 10.1016/j.yrtph.2016.10.001 SchallerJ.-P. KellerD. PogetL. PratteP. KaelinE. McHughD. CudazzoG. SmartD. TrickerA.R. GautierL. YerlyM. Reis PiresR. Le BouhellecS. GhoshD. HoferI. GarciaE. VanscheeuwijckP. MaederS. Evaluation of the Tobacco Heating System 2.2. Part 2: Chemical Composition, Genotoxicity, Cytotoxicity, and Physical Properties of the Aerosol Regul. Toxicol. Pharmacol. 81 2016 S27 S47 10.1016/j.yrtph.2016.10.00127720919 Open DOISearch in Google Scholar

10 Schaller, J.-P., J.P. Pijnenburg, A. Ajithkumar, and A.R. Tricker: Evaluation of the Tobacco Heating System 2.2. Part 3: Influence of the Tobacco Blend on the Formation of Harmful and Potentially Harmful Constituents of the Tobacco Heating System 2.2 Aerosol; Regul. Toxicol. Pharmacol. 81 (2016) S48–S58. DOI: 10.1016/j.yrtph.2016.10.016 SchallerJ.-P. PijnenburgJ.P. AjithkumarA. TrickerA.R. Evaluation of the Tobacco Heating System 2.2. Part 3: Influence of the Tobacco Blend on the Formation of Harmful and Potentially Harmful Constituents of the Tobacco Heating System 2.2 Aerosol Regul. Toxicol. Pharmacol. 81 2016 S48 S58 10.1016/j.yrtph.2016.10.01627793747 Open DOISearch in Google Scholar

11 Smith, M.R., B. Clark, F. Lüdicke, J.-P. Schaller, P. Vanscheeuwijck, J. Hoeng, and M.C. Peitsch: Evaluation of the Tobacco Heating System 2.2. Part 1: Description of the System and the Scientific Assessment Program; Regul. Toxicol. Pharmacol. 81 (2016) S17–S26. DOI: 10.1016/j.yrtph.2016.07.006 SmithM.R. ClarkB. LüdickeF. SchallerJ.-P. VanscheeuwijckP. HoengJ. PeitschM.C. Evaluation of the Tobacco Heating System 2.2. Part 1: Description of the System and the Scientific Assessment Program Regul. Toxicol. Pharmacol. 81 2016 S17 S26 10.1016/j.yrtph.2016.07.00627450400 Open DOISearch in Google Scholar

12 Wong, E.T., U. Kogel, E. Veljkovic, F. Martin, Y. Xiang, S. Boue, G. Vuillaume, P. Leroy, E. Guedj, G. Rodrigo, N.V. Ivanov, J. Hoeng, M.C. Peitsch, and P. Vanscheeuwijck: Evaluation of the Tobacco Heating System 2.2. Part 4: 90-Day OECD 413 Rat Inhalation Study with Systems Toxicology Endpoints Demonstrates Reduced Exposure Effects Compared with Cigarette Smoke; Regul. Toxicol. Pharmacol. 81 Suppl. 2 (2016) S59–S81. DOI: 10.1016/j.yrtph.2016.10.015 WongE.T. KogelU. VeljkovicE. MartinF. XiangY. BoueS. VuillaumeG. LeroyP. GuedjE. RodrigoG. IvanovN.V. HoengJ. PeitschM.C. VanscheeuwijckP. Evaluation of the Tobacco Heating System 2.2. Part 4: 90-Day OECD 413 Rat Inhalation Study with Systems Toxicology Endpoints Demonstrates Reduced Exposure Effects Compared with Cigarette Smoke Regul. Toxicol. Pharmacol. 81 Suppl. 2 2016 S59 S81 10.1016/j.yrtph.2016.10.01527793746 Open DOISearch in Google Scholar

13 Zha, Q. and S. Moldoveanu: The Influence of Cigarette Moisture to the Chemistry of Particulate Phase Smoke of a Common Commercial Cigarette; Beitr. Tabakforsch. Int. 21 (2004) 184–191. DOI: 10.2478/cttr-2013-0779 ZhaQ. MoldoveanuS. The Influence of Cigarette Moisture to the Chemistry of Particulate Phase Smoke of a Common Commercial Cigarette Beitr. Tabakforsch. Int. 21 2004 184 191 10.2478/cttr-2013-0779 Open DOISearch in Google Scholar

14 International Organization for Standardization (ISO): ISO 3402:1999: Tobacco and Tobacco Products – Atmosphere for Conditioning and Testing; ISO, Geneva, Switzerland, 2015. International Organization for Standardization (ISO) ISO 3402:1999: Tobacco and Tobacco Products – Atmosphere for Conditioning and Testing ISO Geneva, Switzerland 2015 Search in Google Scholar

15 World Health Organization (WHO): Stability Testing of Active Pharmaceutical Ingredients and Finished Pharmaceutical Products; Annex 2, WHO Technical Report Series 953 (2009) 87–123. Available at: http://digicollection.org/hss/documents/s19133en/s19133en.pdf (accessed April, 2021) World Health Organization (WHO) Stability Testing of Active Pharmaceutical Ingredients and Finished Pharmaceutical Products Annex 2, WHO Technical Report Series 953 (2009) 87–123. Available at: http://digicollection.org/hss/documents/s19133en/s19133en.pdf (accessed April, 2021) Search in Google Scholar

16 Goujon, C., S. Kleinhans, S. Maeder, L. Poget, and J.-P. Schaller: Robustness of HPHC Reduction for THS 2.2 Aerosol Compared with 3R4F Reference Cigarette Smoke Under High Intensity Puffing Conditions; Beitr. Tabakforsch. Int. 29 (2020) 66–83. DOI: 10.2478/cttr-2020-0008 GoujonC. KleinhansS. MaederS. PogetL. SchallerJ.-P. Robustness of HPHC Reduction for THS 2.2 Aerosol Compared with 3R4F Reference Cigarette Smoke Under High Intensity Puffing Conditions Beitr. Tabakforsch. Int. 29 2020 66 83 10.2478/cttr-2020-0008 Open DOISearch in Google Scholar

17 Djordjevic, M.V., S.D. Stellman, and E. Zang: Doses of Nicotine and Lung Carcinogens Delivered to Cigarette Smokers; J. Natl. Cancer Inst. 92 (2000) 106–111. DOI: 10.1093/jnci/92.2.106 DjordjevicM.V. StellmanS.D. ZangE. Doses of Nicotine and Lung Carcinogens Delivered to Cigarette Smokers J. Natl. Cancer Inst. 92 2000 106 111 10.1093/jnci/92.2.10610639511 Open DOISearch in Google Scholar

18 World Health Organization (WHO): WHO Study Group on Tobacco Product Regulation: Report on the Scientific Basis of Tobacco Product Regulation, Fifth Report, WHO Technical Report Series 989 (2015). Available at: https://escholarship.org/content/qt81m4m677/qt81m4m677.pdf (accessed April, 2021) World Health Organization (WHO) WHO Study Group on Tobacco Product Regulation: Report on the Scientific Basis of Tobacco Product Regulation, Fifth Report, WHO Technical Report Series 989 (2015) Available at: https://escholarship.org/content/qt81m4m677/qt81m4m677.pdf (accessed April, 2021) Search in Google Scholar

19 Poget, L., P. Campelos, C. Jeannet, and S. Maeder: Development of Models for the Estimation of Mouth Level Exposure to Aerosol Constituents from a Heat-Not-Burn Tobacco Product Using Mouthpiece Analysis; Beitr. Tabakforsch. Int. 27 (2017) 42–64. DOI : 10.1515/cttr-2017-0005 PogetL. CampelosP. JeannetC. MaederS. Development of Models for the Estimation of Mouth Level Exposure to Aerosol Constituents from a Heat-Not-Burn Tobacco Product Using Mouthpiece Analysis Beitr. Tabakforsch. Int. 27 2017 42 64 10.1515/cttr-2017-0005 Open DOISearch in Google Scholar

20 Chen, Z., Q. Miao, J. Zhao, L. Ding, Y. Xiao, H. Wang, Y. Qin, W. Xiong, H. Tao, Y. Wang, X. Lv, and Q. Feng: Conditioning of Tobacco and Tobacco Products: The Effect of Forced Air Flow; Beitr. Tabakforsch. Int. 28 (2019) 224–229. DOI: 10.2478/cttr-2019-0003 ChenZ. MiaoQ. ZhaoJ. DingL. XiaoY. WangH. QinY. XiongW. TaoH. WangY. LvX. FengQ. Conditioning of Tobacco and Tobacco Products: The Effect of Forced Air Flow Beitr. Tabakforsch. Int. 28 2019 224 229 10.2478/cttr-2019-0003 Open DOISearch in Google Scholar

21 Government of Canada: Canadian Tobacco Reporting Regulations: 2000-07-19 Canada Gazette Part II, Vol. 134, No. 15 Part 3: Emissions from Designated Tobacco Products. Available at: http://www.hc-sc.gc.ca/hl-vs/tobac-tabac/legislation/reg/indust/index_e.html (accessed April, 2021). Government of Canada Canadian Tobacco Reporting Regulations: 2000-07-19 Canada Gazette Part II, Vol. 134, No. 15 Part 3: Emissions from Designated Tobacco Products Available at: http://www.hc-sc.gc.ca/hl-vs/tobac-tabac/legislation/reg/indust/index_e.html (accessed April, 2021). Search in Google Scholar

22 International Organization for Standardization (ISO): ISO/IEC 17025:2005: General Requirements for the Competence of Testing and Calibration Laboratories; ISO, Geneva, Switzerland, 2017. International Organization for Standardization (ISO) ISO/IEC 17025:2005: General Requirements for the Competence of Testing and Calibration Laboratories ISO Geneva, Switzerland 2017 Search in Google Scholar

23 Gelman, A., J.B. Carlin, H.S. Stern, D.B. Dunson, A. Vehtari, and D.B. Rubin: Bayesian Data Analysis; Third Edition, Chapman and Hall, CRC Press, 2013. Available at: https://statisticalsupportandresearch.files.wordpress.com/2017/11/bayesian_data_analysis.pdf (accessed May, 2021) GelmanA. CarlinJ.B. SternH.S. DunsonD.B. VehtariA. RubinD.B. Bayesian Data Analysis Third Edition Chapman and Hall, CRC Press 2013 Available at: https://statisticalsupportandresearch.files.wordpress.com/2017/11/bayesian_data_analysis.pdf (accessed May, 2021) 10.1201/b16018 Search in Google Scholar

24 Kruschke, J.: Doing Bayesian Data Analysis: A Tutorial with R, JAGS, and Stan; 2^nd Edition, Academic Press, Cambridge, Massachusetts, USA, 2014. ISBN: 9780124059160 KruschkeJ. Doing Bayesian Data Analysis: A Tutorial with R, JAGS, and Stan 2nd Edition Academic Press Cambridge, Massachusetts, USA 2014 ISBN: 9780124059160 Search in Google Scholar

25 Robert, C.P. and G. Casella: Introducing Monte Carlo Methods with R; Springer, New York, NY, USA, 2010, Vol. 18. ISBN: 978-1-4419-1576-4 RobertC.P. CasellaG. Introducing Monte Carlo Methods with R Springer New York, NY, USA 2010 18 ISBN: 978-1-4419-1576-4 10.1007/978-1-4419-1576-4 Search in Google Scholar

26 Littell, R.C., G.A. Milliken, W.W. Stroup, R.D. Wolfinger, and O. Schabenberger: SAS® for Mixed Models; SAS Institute, Cary, NC, USA, 2006. ISBN: 159047-500-3 LittellR.C. MillikenG.A. StroupW.W. WolfingerR.D. SchabenbergerO. SAS® for Mixed Models SAS Institute Cary, NC, USA 2006 ISBN: 159047-500-3 Search in Google Scholar

27 West, B.T., K.B. Welch, and A.T. Galecki: Linear Mixed Models: A Practical Guide Using Statistical Software, 2^nd Edition; Chapman and Hall/CRC Press, Boca Raton, FL, USA, 2014. ISBN 9781466560994 WestB.T. WelchK.B. GaleckiA.T. Linear Mixed Models: A Practical Guide Using Statistical Software 2nd Edition Chapman and Hall/CRC Press Boca Raton, FL, USA 2014 ISBN 9781466560994 10.1201/b17198 Search in Google Scholar