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BMJ WHO Rapid Response

WHO urges restrictions on e-cigarettes
BMJ 2016; 355 doi: (Published 08 November 2016) Cite this as: BMJ 2016;355:i5991

Teen vaping is linked to higher odds of heavy cigarette smoking
BMJ 2016; 355 doi: (Published 09 November 2016) Cite this as: BMJ 2016;355:i6025

BMJ WHO Rapid Response.

Anne Gulland’s BMJ article on electronic cigarettes (1), initially, merely confirms detail that academic advocates of the potential benefits of e-cigarettes have postulated, for example, those at the National Centre for Smoking Cessation and Training (NCSCT: 2). Moreover, the issues related to flavourings, and appreciable health risk, are also highlighted by the NCSCT. As they currently state:

“There are some flavours where a degree of risk is established and so these flavours should be avoided. For example, chronic exposure to diacetyl which gives a buttery flavour (butterscotch flavour has already been voluntarily withdrawn by some manufacturers), caused irreversible bronchiolitis in workers at a microwave popcorn plant.

There is also some evidence that cinnamon flavours are cytotoxic.”

The presence of diacetyl has been confirmed in many brands, and its risks are established (3; 4), as is the presence of benzaldehyde in cherry flavoured fluids (5; 6) and cinnamaldehyde in cinnamon flavours. Moreover, levels of aldehydes (e.g. formaldehyde, acetaldehyde and acrolein), significantly above those deemed to be “safe”, have further very recently been identified, although, these findings need to be confirmed via replication. What is true is that testing of e-cigarette fluids (and subsequent aerosol), that have, potentially at least, been available consumers for some considerable time, is incomplete, but on-going. As one toxicological testing organisation (“bibra”) involved in this have stated:

“A wide array of flavouring substances are added to electronic cigarette formulations and these might be inhaled (along with nicotine and other excipients) by the consumer. The toxicological acceptability of such substances has historically been assessed for food and cosmetics applications, and their safety for use in electronic cigarettes (as inhaled flavourings) now needs to be substantiated.”

This issue is important for all users, and potential users of e-cigarettes, to appreciate, if they are to be allowed to make as fully an informed choice as possible. The evidence on flavours currently available is incomplete, for, as Gulland identifies, there are many thousands of flavours available.

The WHO correctly confirm that e-cigarettes are “likely” to be less harmful than conventional cigarettes and tobacco, and their statement that:

“No specific figure about how much ‘safer’ the use of these products is compared to smoking can be given any scientific credibility at this time,” is, indeed, substantiated by expert toxicological opinion (11; 12).

The WHO’s interpretation of the currently available evidence base related to cessation being “scant and of low certainty, making it difficult to draw credible inferences” is accurate. Although Gulland cites the Cochrane Review (13) for finding that e-cigarettes do help smokers to quit, the Review, itself, states that, regarding the only two suitable randomised controlled trials currently available: “under GRADE system we rated overall quality of the evidence for our outcomes as ‘low’ or ‘very low’.”

The results are, further, clearly short term, and therefore, no long term data relating to serious side effects is currently available. However, the Lead for the Royal College of Physician’s Tobacco Advisory Group John Britton and colleagues (14) has stated that: “e-cigarettes are unlikely to be harmless . . . long term use is likely to be associated with long term sequelae, including an increased risk of chronic obstructive pulmonary disease, lung cancer, possibly cardiovascular disease, and some other long term conditions associated with smoking.”

It, therefore, appears appropriate and proportionate, considering the points above related to these potentially addictive devices, that, as Gulland articulates it: “WHO said that countries should consider banning the sale and distribution of e-cigarettes to minors and should ban or restrict the use of flavours that might appeal to minors.”

Moreover, the WHO position on the highly suspicious strategy of the tobacco industry, and its involvement in the manufacture and marketing of e-cigarettes, is fully supported: firstly, by the Royal College of Physicians, in their “Nicotine without smoke” document (15); plus secondly, by the very recent publication of a review of the tobacco industry’s own history of “developments” of “safer cigarettes” since 1990, but as a complement to, as opposed to competitor with, cigarettes (16).

David Bareham

All views are of the author alone, and do not necessarily reflect those of his employer.

DB has delivered 3 presentations to local clinicians in Lincolnshire within the last 18 months entitled: “E-cigarettes: update on evidence”, organised by GlaxoSmithKline. No payment was requested nor provided for this work.

1) Gulland, A. WHO urges restrictions on e-cigarettes. British Medical Journal. Available at:
2) National Centre for Smoking Cessation and Training. Electronic cigarettes: A briefing for stop smoking services. Available at:
3) Allen et al. Flavoring Chemicals in E-Cigarettes: Diacetyl, 2,3-Pentanedione, and Acetoin in a Sample of 51 Products, Including Fruit-, Candy-, and Cocktail-Flavored E-Cigarettes. Environ Health Perspect. 124; 6. 733 – 739. DOI:10.1289/ehp.1510185 (2016)
4) Kreiss, K. et al. Clinical bronchiolitis obliterans in workers at a microwave-popcorn plant. N. Engl. J. Med. 347, 330–338 (2002).
5) Kosmider et al. Cherry-flavoured electronic cigarettes expose users to the inhalation irritant, benzaldehyde. Thorax. 0:1–2. DOI: 10.1136/thoraxjnl-2015-207895 (2016)
6) Bahl, V. et al. Comparison of electronic cigarette refill fluid cytotoxicity using embryonic and adult models. Reprod. Toxicol. 34, 529–537 (2012).
7) Behar, R. et al. Tob Control. Distribution, quantification and toxicity of cinnamaldehyde in electronic cigarette refill fluids and aerosols0:1–9. doi:10.1136/tobaccocontrol-2016-053224 (2016).
8) Khlystov, A and Samburova, V. Flavoring Compounds Dominate Toxic Aldehyde Production During E-cigarette Vaping. Environ. Sci. Technol. DOI: 10.1021/acs.est.6b05145 (2016).
9) Electronic Cigarette Industry trade Association. 2016. The Toxicology Collaboration Project: FAQs. Available at:
10) bibra Toxicology Advice and Consulting. Provision of Hazard and Risk Assessments for Several Flavourings in Electronic Cigarettes. A:
11) Wilson, N., Gartner, C., and Edwards, R. Available at:
12) Combes, R. and Balls, M. Available at:
13) Cochrane Review of Electronic Cigarettes for Smoking Cessation DOI: 10.1002/14651858.CD010216.pub3
14) Britton, J., Arnott, D., McNeill, A., Hopkinson, N. Nicotine without smoke—putting electronic cigarettes in context. BMJ 2016; 353
15) Royal College of Physicians. (2016) Nicotine without smoke: Tobacco harm reduction. London: RCP
16) Dutra LM, Grana R, Glantz SA. Philip Morris research on precursors to the modern e-cigarette since 1990. Tob Control Published Online First: 2016; DOI:10.1136/tobaccocontrol-2016-053406

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