ATLA 43, 361–362, 2015
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Editorial Do E-cigarettes Pose a Risk to Human Health? Gerry Kenna
The claim by Public Health England that e-cigarettes have no concerning adverse health effects is flawed, because it is not evidence based
In a Comment featured in this issue of ATLA,1 Robert Combes and Michael Balls challenge the recent assertions by Public Health England that “…e-cigarette use is around 95% less harmful to health than smoking” and that “…e-cigarettes have the potential to help smokers quit smoking”.2 They point out that the position adopted by Public Health England on e-cigarette safety is not evidence based, mainly because it is not supported by a scientifically rigorous risk assessment. This matters, because e-cigarette use is increasing rapidly in the UK and in many developed countries, whilst the smoking of tobacco has decreased.1 The use of e-cigarettes will raise no concern if it is truly safe. However, were e-cigarette smoking to be unsafe, the adverse health consequences could prove to be substantial. Furthermore, Combes and Balls propose that human risk assessment of e-cigarettes should be undertaken by using a novel approach that does not require toxicity studies in experimental animals, which they have described in detail previously.3 Not too long ago, cigarette smoking was common across the populations of many countries. This was because tobacco-based products are highly addictive, the products themselves were relatively cheap, access to them was poorly regulated, and their role in initiating human diseases was complex and so was difficult to establish. The first clear evidence linking tobacco smoking to human ill-health was uncovered by Sir Richard Doll in 1950, following a methodical case study of possible explanations for the recent massive increase in the frequency of lung cancer in the UK population.4 His pioneering work was not immediately accepted and acted upon, but was followed by further longterm prospective epidemiological studies. These confirmed an unequivocal causal relationship between smoking and lung cancer, and also revealed strong associations between smoking and chronic obstructive pulmonary disease, ischaemic heart disease and markedly reduced life expectancy.5
Subsequently, Doll’s original findings were confirmed by others, and led to the recognition that cigarette smoking is the single largest avoidable cause of ill-health and fatality in developed nations. Eventually, governmental actions were taken in the UK and many other developed countries, which were intended to limit and reduce cigarette consumption and ensure it is restricted only to consenting adults. Hence, the prominent labelling of health risks on packs of cigarettes and other tobacco-based products, restrictions on advertising, high taxation, restrictions on vendors, and, most recently, the banning of cigarette smoking in public spaces. Bans on smoking in public places enable all of the population to breathe cleaner air, which is not polluted by tobacco smoke. The bans have also yielded valuable additional insight into the impact of smoking on health, by enabling comparisons to be made before and after their implementation. The results are striking: One meta-analysis of the health impact of 33 smoke-free laws, with a median follow up of 24 months, revealed that comprehensive smoking bans were associated with markedly reduced rates of hospital admissions or deaths due to coronary events (relative risk: 0.848), other heart diseases (relative risk: 0.610), cerebrovascular accidents (relative risk: 0.840) or respiratory diseases (relative risk: 0.760).6 A major problem confronting those wishing to achieve still further reductions in cigarette smoking-related human ill-health, is the highly addictive nature of the habit, which means that many smokers try to quit, but fail. The cause of the addiction is nicotine7 and e-cigarettes are designed to provide convenient inhalational delivery of nicotine vapour without exposing the user to very many of the thousands of other chemicals present in tobacco smoke, some of which are highly toxic.8 Based on scientific first principles, it is reasonable to presume that e-cigarette use could well be safer than cigarette smoking. However, it is unreasonable at the present time to assume that e-cigarette use is safe and therefore should be pro-
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moted to help current smokers to reduce and ideally stop smoking, as has been proposed by Public Health England.2 The relatively high levels of nicotine present in e-cigarette vapour cause concern, since nicotine exerts potent pharmacological effects on the cardiovascular system and other systems and also has many additional adverse biological effects, as do the other hazardous chemicals to which users of e-cigarettes will be exposed. Therefore an evidence-based assessment of the human health risk posed by e-cigarettes is needed.1,3 But which data are most suitable for this purpose? Combes and Balls propose that an integrated scheme, which includes chemical analyses, physiologically-relevant organotypic human in vitro models, physiologically-based in vitro–in vivo exposure scaling, and human in vivo clinical investigations, should be used to quantify in vitro hazards posed by chemicals present in e-cigarettes and to assess their risk to humans.1,3 These could be complemented by prospective phase 1-type clinical studies involving biomarkers of exposure and effect, which could be augmented by prospective investigations on the health of e-cigarette users, cigarette smokers and non-smokers, of the type pioneered by Sir Richard Doll.5 When compared with the more classical toxicological strategy of long-term toxicity studies in animals, followed by human safety assessment via physiologically-based cross-species in vivo exposure modelling, the mechanistic approach set out by Combes and Balls has many scientific and pragmatic advantages. Also, it is aligned fully with the Three Rs principles. Let us hope that it is adopted by the scientific community and gains regulatory and governmental support, so that we can be informed of whether e-cigarettes really are as safe and useful as some would have us believe.2
Editorial
Dr Gerry Kenna Scientific Director FRAME Russell & Burch House 96−98 North Sherwood Street Nottingham NG1 4EE UK E-mail:
[email protected]
References 1 Combes,
R.D. & Balls, M. (2015). On the safety of E-cigarettes: “I can resist anything except temptation”. ATLA 43, 417–425 2 Anon. (2015). E-cigarettes: A new foundation for evidence-based policy and practice, 6pp. Available at: https://www.gov.uk/government/uploads/system/uploads/ attachment_data/file/454517/Ecigarettes_a_firm_ foundation_for_evidence_based_policy_and_practice. pdf (Accessed 23.12.15). 3 Combes, R.D. & Balls, M. (2015). A critical assessment of the scientific basis, and implementation, of regulations for the safety assessment and marketing of innovative tobacco-related products. ATLA 43, 251–290. 4 Doll, R. & Hill, A.B. (1950). Smoking and carcinoma of the lung. Preliminary Report. BMJ 2, 739–748. [Also available at: Bulletin of the World Health Organisation 77, 84–93 (1999).] 5 Doll, R., Peto, R., Boreham, J. & Sutherland, I. (2004). Mortality in relation to smoking: 50 years’ observations on male British doctors. BMJ 328, 1519–1528. 6 Tan, C.E. & Glantz, S.A. (2012). Association between smoke-free legislation and hospitalizations for cardiac, cerebrovascular, and respiratory diseases: A metaanalysis. Circulation 126, 2177–2183. 7 Benowitz, N.L. (2009). Pharmacology of nicotine: Addiction, smoking-induced disease, and therapeutics. Annual Review of Pharmacology & Toxicology 49, 57–71. 8 Talhout, R., Schulz, T., Florek, E., van Benthem, J., Wester, P. & Opperhuizen, A. (2011). Hazardous compounds in tobacco smoke. International Journal of Environmental Research & Public Health 8, 613–628.
