WHO Technical Report Series 1029 WHO study group on tobacco product regulation Report on the scientific basis of tobacco product regulation: eighth report of a WHO study group WHO was established in 1948 as a specialized agency of the United Nations serving as the directing and coordinating authority for international health matters and public health. One of WHO’s constitutional functions is to provide objective, reliable information and advice in the field of human health, a responsibility that it fulfils in part through its extensive programme of publications. The Organization seeks through its publications to support national health strategies and address the most pressing public health concerns of populations around the world. 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The responsibility for the interpretation and use of the material lies with the reader. In no event shall WHO be liable for damages arising from its use. This publication contains the collective views of an international group of experts and does not necessarily represent the decisions or the policies of WHO. Contents Participants in the 10th meeting of the WHO study group on tobacco product regulation ix Acknowledgements xiii Abbreviations and acronyms xiv 1. Introduction 1 2. Toxicants in heated tobacco products, exposure, health effects and claims of reduced risk 7 Abstract 7 2.1 Background 8 2.2 Toxicants in heated tobacco product (HTP) emissions 10 2.2.1 Laboratory methods for measuring toxicants 10 2.2.2 Nicotine 11 2.2.3 Other toxicants 13 2.3 Exposure and effects of HTPs in vitro and in laboratory animals 20 2.3.1 In-vitro studies 20 2.3.2 Studies in laboratory animals 22 2.4 Exposure of humans to toxicants in HTPs and implications for health 24 2.4.1 Product use and topography 24 2.4.2 Biomarkers of exposure and effect 25 2.4.3 Passive exposure 29 2.4.4 Impact on health outcomes 31 2.5 Review of the evidence for reduced risk or harm with use of HTPs 33 2.5.1 Harm reduction in the context of tobacco products 33 2.5.2 Claims of reduced risk 33 2.6 Summary and implications for public health 37 2.6.1 Summary of data 37 2.6.2 Implications for public health 39 2.7 Research gaps and priorities 40 2.8 Policy recommendations 41 2.9 References 41 3. The attractiveness and addictive potential of heated tobacco products: effects on perception and use and associated effects 49 Abstract 49 3.1 Background 50 3.2 Attractiveness of heated tobacco products (HTPs) 52 3.2.1 Definitions of attractiveness in the context of Articles 9 and 10 of the WHO FCTC 52 3.2.2 Attractive features of HTPs 52 3.2.3 What we can learn from ENDS and ENNDS and relevance to HTPs 56 3.3 Addictiveness of HTPs 57 3.3.1 Addictiveness 57 3.3.2 What can we learn from ENDS and ENNDS and relevance to HTPs 61 3.3.3 Overall abuse liability of HTPs 61 iii 3.4 Effects of the attractiveness and addictiveness of ENDS, ENNDS and HTPs on perceptions of risk and harm and use 62 3.4.1 Contributions of attractiveness and addictiveness to initiation, switching, complementing and quitting conventional tobacco products 62 3.4.2 Learning from ENDS and ENNDS and application to HTPs 63 3.5 Discussion 64 3.5.1 Behavioural implications of different patterns of use among different groups 64 3.5.2 Implications for public health 65 3.5.3 Research gaps, priorities and questions 66 3.5.4 Policy recommendations 67 3.6 Conclusions 68 3.7 References 68 Annex 3.1. Menthol concentrations in IQOS, cigarettes and JUUL products 74 4. Variations among heated tobacco products: considerations and implications 75 Abstract 75 4.1 Background 76 4.1.1 Overview 76 4.1.2 Decision FCTC/COP8(22) of the Conference of the Parties 76 4.1.3 Scope and objectives 76 4.2 Variations among products on the market 77 4.2.1 Overview of product categories and types 77 4.2.2 Variations among heated tobacco products 79 4.2.3 Market distribution of product types and categories 79 4.3 Characteristics and design features of products 81 4.3.1 Temperature profiles of products and operational capabilities 81 4.3.2 Battery characteristics 81 4.3.3 Properties of tobacco inserts, sticks and capsules 81 4.4 Content, emissions and general design of products 82 4.4.1 Content and emissions 82 4.4.2 Nicotine delivery 85 4.4.3 Risk profiles 85 4.4.4 Regulatory implications of the contents of heated tobacco products 86 4.4.5 Regulatory implications of emissions 87 4.5 Variations among products, manufacturers and selling points 88 4.5.1 Manufacturers and selling points 88 4.5.2 Implications for customer pulling power 89 4.6 Discussion 90 4.7 Conclusions 91 4.8 Research gaps, priorities and questions 92 4.9 Policy recommendations 92 4.10 References 94 5.