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Objective: Some additives counteract the harshness and bitterness of the aerosols of tobacco and nicotine products (TNPs), making them easier to inhale. This is a problem for public health, as it may stimulate the uptake and continued use of TNPs, especially by young people. This paper provides a conceptual framework of the processes, mechanisms and methods for assessing inhalation facilitation (IF). Specific additives in TNPs that may promote IF are reviewed and their potential health impact discussed. Methods: A targeted (non-systematic) search of PubMed and other bibliographic sources with no restrictions on time period, up to September 2022, included terms related to IF processes (e.g. “harshness”, “puff duration”), candidate additives (e.g. “menthol”) or candidate mechanisms (e.g. “TRPM8 [transient receptor potential cation channel, family 8] receptor”). Inclusion of studies in the review was agreed by consensus by the two authors. Results: We defined IF as a modification to a TNP that improves the user’s sensory experience of inhaling the product’s aerosol (reduced bitterness and harshness) and may alter inhalation behaviour, particularly more intense inhalation (e.g. deeper puffs, faster inhalation, larger puff volume) and also restoration of breathing patterns that are disturbed by inhaled irritants. The review showed that: (a) menthol and synthetic coolants decrease the irritation caused by nicotine and other TNP aerosol constituents by activating TRPM8 and other receptors and may promote dependence in inexperienced users; (b) acid additives and sugars, which yield acids upon combustion, lower the “pH” of TNP aerosol, resulting in higher levels of protonated nicotine, which is perceived as less harsh than free-base nicotine and may increase blood nicotine levels; (c) sweet flavourings in e-cigarettes reduce perceptions of bitterness and may escalate use, although their effects on perceived harshness are inconclusive; (d) sugars in tobacco impart sweet flavour sensations, but limited industry-independent data preclude a strong conclusion for IF; (e) some effects of additives on IF are amplified in non-smokers and younger populations; and (f) studies should be conducted on inhalation behaviour. Conclusions: Several additives may facilitate inhalation of tobacco smoke and/or e-cigarette aerosol by improving the sensory experience. IF additives may increase nicotine blood levels, dependence and, in some cases, inhalation behaviour, especially in young people and non-smokers. Further research on the effects of TNP additives on sensory attributes and inhalation behaviour may provide useful evidence for regulatory policy. [ABSTRACT FROM AUTHOR]

This paper focuses specifically on the relationship between World Trade Organization (WTO) agreements and American regulation of food products and additives. Section I provides background information on how the United States regulates domestic and imported food products. Section II explains the nature of the WTO agreements and the WTO dispute settlement process; discusses the WTO dispute between the EU, Canada, and the US over administration of growth hormones to increase beef production (Meat Hormones); reveals parallel domestic issues in the US regarding scientific uncertainty and the effect of federalism on state sovereignty; and considers the relationship between food regulation and environmental ethics in the context of three WTO panel reports (Tuna I, Tuna 11, and Shrimp). Finally, Section III considers the domestic policy implications of the WTO agreements as interpreted by the WTO dispute settlement body and applied in the context of food; and makes recommendations as to how concerned parties should continue to act, at both the national and international levels, to address the difficult issues raised in the Meat Hormones, Tuna, and Shrimp disputes.