On 23 September 2020, the European Commissions’ Scientific Committee on Health, Environmental and Emerging Risks (SCHEER) issued its Preliminary Opinion on electronic cigarettes at a request from the Commission “to assist the Commission in assessing the most recent scientific and technical information on e-cigarettes. Findings presented in the scientific opinion will feed into the Commission’s reporting obligations under Article 28 of the Tobacco Products Directive (TPD), and will also help the Commission in assessing the potential need for legislative amendments under the Directive or other regulatory/enforcement measures.”
The preliminary opinion (report) was put out for public comment with a deadline for commenting of 26 October 2020. I found out about the report from a press release from BAT complaining about the report and submitting BAT’s criticisms. (More about this later.) By then it was too late to submit additional comments.
The report is moving quickly; SCHEER hoped to deliver the final report to the Commission by 31 October 2020 so that it can inform the Commission’s reporting requirements due 20 May 2021.
This is a huge undertaking; when I searched PubMed for “e-cigarette” I got 5,631 papers. Perhaps to deal with this huge and rapidly growing literature, the SCHEER compiled information mainly from review articles published between January 2015 and April 2019, supplemented by primary sources and literature beyond this period. This was a sensible approach. The problem is, however, that, given publication delays those review papers probably covered papers published up until mid-to-late 2018, two years ago.
And two years is a lifetime in e-cigarette research, where knowledge about risks is rapidly accumulating. (As I said, SCHEER also cited papers after 2018, but they did not capture everything.)
Another thing which is a bit different from how other consensus reports have evaluated e-cigarettes, with the exception of behavioral outcomes (gateway effects for youth and young adults and quitting for adults), the committee focused on selected toxins in e-cigarette aerosol and applied standard risk assessment methodologies to these chemicals.
Here is how they summarize their approach (page 11):
Regarding e-liquid composition, the SCHEER focusses in this Opinion on i) nicotine, ii) carriers (e.g. glycerol and propylene glycol) considered of high importance and present with high frequency at high levels and iii) ingredients present in more than 10% of products tested with a median amount > 1 mg or present in less than 10 % of products tested but with a median amount of > 10 mg, according to lists of most common ingredients of e-liquids from competent authorities compilation. The great majority of chemicals other than nicotine and carriers (e.g. glycerol and propylene glycol) are flavourings. The categories containing the highest number of e-liquids were fruit (34%) and tobacco (16%).
In order to evaluate the health risks related to the use of electronic cigarettes, the SCHEER follows different lines of evidence. For the risk assessment, the exposure and the hazard profile of major aerosol constituents is described. The SCHEER considers also human data on health impacts on users of electronic cigarettes from epidemiological studies or clinical trials. The SCHEER is of the opinion that chemicals present in the aerosol are mainly responsible for possible health effects for users of electronic cigarettes. Further potential health effects associated with the use of electronic cigarettes are poisoning from ingestion of liquid nicotine, particularly by young children as well as injuries due to burns and 24 explosions.
The committee then used data on puffing patterns to estimate doses of these chemicals and the associated health effects following well-established procedures from environmental risk assessment.
Here is what they concluded (Abstract, page 2):
The SCHEER concludes that on health effects
a) for users of electronic cigarettes
1. the overall weight of evidence for risks of local irritative damage to the respiratory tract is i) moderate or heavy users of electronic cigarette due to the 10cumulative exposure to polyols, aldehydes and nicotine, and ii) not to be excluded for average and light users. However, the overall reported incidence is low.
2.the overall weight of evidence for risks of long-term systemic effects on the cardiovascular system is strong.
3.the overall weight of evidence for risks of carcinogenicity of the respiratory tract due to long-term, cumulative exposure to nitrosamines and due to exposure to 16acetaldehyde and formaldehyde is weak to moderate. The weight of evidence for risks of adverse effects, specifically carcinogenicity, due to metals in aerosols is weak.
4. the overall weight of evidence for risks of poisoning and injuries due to burns and explosion, is strong. However, the incidence is low.
5. the overall weight of evidence for risks of other long-term adverse health effects, such as pulmonary disease, CNS and reprotoxic effects, plausible based on the hazard identification and limited human evidence, cannot be established due to lack of consistent data.
6. to date, there is no specific data that specific flavourings used in the EU pose health risks for electronic cigarette users following repeated exposure (but may enhance attractiveness).
b) for second-hand exposed persons
1.the overall weight of evidence is moderate for risks of local irritative damage to the respiratory tract.
2. the overall weight of evidence for risks of systemic cardiovascular effects in second-hand exposed persons due to exposure to nicotine is weak to moderate.
3.The overall weight of evidence for carcinogenic risk due to cumulative exposure to nitrosamines is weak to moderate.
Electronic cigarettes are relatively new in terms of exposure to humans. More research is needed, in particular on long-term health effects.
Regarding the role of electronic cigarettes as a gateway to smoking/the initiation of smoking, particularly for young people, the SCHEER concludes that there is strong evidence that electronic cigarettes are a gateway to smoking for young people. There is also strong evidence that nicotine in e-liquids is implicated in the development of addiction and that flavours have a relevant contribution for attractiveness of use of electronic cigarette and initiation.
Regarding the role of electronic cigarettes in cessation of traditional tobacco smoking, the SCHEER concludes that there is weak evidence for the support of electronic cigarettes’ effectiveness in helping smokers to quit while the evidence on smoking reduction is assessed as weak to moderate.
Given the approach that SCHEER took, these are reasonable and solid conclusions.
A few comments:
- The conclusion that the evidence that e-cigarettes help people quit smoking is weak is important because it further undermines the industry’s claim that e-cigarettes help people quit smoking cigarettes. This is especially important because, like other assessments of this question, the committee looked to randomized controlled trials which are designed to assess medicines rather than consumer products. RCTs generally give more optimistic assessments of interventions because the participants are carefully selected and monitored, compare the unsupervised use as an unsupervised consumer product. The committee (and everyone else) needs to pay more attention to this distinction.
- The conclusion that e-cigarettes are a gateway toward smoking is the latest nail in this coffin. Khouja et al’s high quality meta-analysis of the gateway effect (which is not cited in the SCHEER report probably because it was published too late to include) reinforces this conclusion because it shows similar gateway effects across countries, including Germany and the Netherlands, as well as UK) shows I don’t expect industry to give up on this argument anytime soon, but it would certainly be nice for the few remaining people in the health community to accept this reality.
- The conclusions about health effects are based on the limited number of e-cig aerosol that the committee considered. The recent research looking at the effects of whole aerosol show even bigger effects.
- The committee did not examine the specific toxicity of many flavors because they are not major (in terms of the absolute amounts of flavoring agents used); recent research is showing major pulmonary and cardiovascular toxicity of many flavors.
- The decision not to consider nanoparticles, while understandable in terms of the committee’s overall response, is almost certainly to underestimate the cardiovascular and pulmonary effects of e-cigarette aerosol exposure.
- There is little discussion of the human epidemiological studies showing adverse pulmonary and cardiovascular effects of e-cigarettes, perhaps because this work appeared too late to be considered.
- There is no discussion of the effects of dual use (using e-cigarettes and cigarettes at the same time); there is emerging evidence that dual use is more dangerous than using either product alone.
If there is time, the opinion would be further strengthened by integrating these points.
BAT’s response
As I noted above, BAT submitted extensive comments, which you can read here. Here are BAT’s main complaints, taken from its press release:
Fails to contextualize the risks of e-cigarettes relative to those associated with continued smoking
Makes inaccurate claims regarding e-cigarettes many of which have been widely debunked by the scientific and public health communities.
Contains false assumptions that e-cigarette aerosol is the same as tobacco smoke.
Neglects landmark independent studies showing that many smokers view e-cigarettes as an acceptable alternative to smoking.
Relies on data from non-EU markets and studies on products pre-dating the current Tobacco Products Directive that are not relevant to the current EU context.
None of these seriously challenge the SCHEER opinion.
First, the committee was charged with assessing the health and behavioral risks of e-cigarette use, not to do a comparative analysis with cigarettes, which would implicitly accept the industry’s “harm reduction” framing. The reality is that the tobacco companies developed e-cigarettes to hold on to customers (as with industry NRT-like products), not to promote “harm reduction.”
Most important, the harm reduction hypothesis rests on two assumptions that are not being born out in the real world: (1) that the great majority of e-cigarette users will be former smokers, (2) that e-cigarettes are dramatically less dangerous than smoking cigarettes, and that (3) kids will not be attracted to e-cigarettes. The more we learn about actual behavior, the less likely (1) and (2) are and, as SCHEER noted, there is strong and consistent evidence against (3), the so-called gateway effect.
SCHEER did the right thing in not falling into this industry trap.
Second, as noted in my comments on the report, SCHEER cautiously applied well-accepted risk assessment approaches that, if anything, underestimated the risks of e-cigarette use.
Third, the statement that SCHEER assumed e-cigarette aerosol is “the same as tobacco smoke” is not true. As explained earlier, SCHEER did their best to determine the major constituents in e-cigarette aerosol and combined that data with information on puffing patterns to estimate health effects. Again, as noted above, because they did not consider everything in e-cigarette aerosol (most notably nanoparticles), they almost certainly underestimated the health risks.
Fourth, the SCHEER did not ignore the fact that many smokers are trying e-cigarettes. More important, the fact that smokers view e-cigarettes as an acceptable alternative to smoking does not mean that they are safe or effective pathways away from smoking that lower overall risk.
Fifth, BAT is correct that the committee relied on information from outside the EU, most notably from the USA where there has been a lot of research. The committee repeatedly acknowledged this point. The important things, however, that BAT did not demonstrate, is that any of these differences make any material difference in the health or behavioral effects of e-cigarettes.
In addition, as in the USA and everywhere else, there are a huge number of different e-cigarette products, so these differences between EU and elsewhere are probably lost in the noise. The Committee did the right thing.
Complaining about the fact that SCHEER used data from outside the EU is the latest incarnation of an old industry trick of trying to get as much information thrown out so they can argue that more research – not meaningful regulation — is needed.
In addition, BAT included the following uncited statement:
The FDA recently published the Technical Product Lead (TPL) assessment of an MRTP [Modified Risk Tobacco Product] application. In the TPL summary it classed certain HPHCs according to disease relevant toxicity. In terms of cardiovascular toxicity, Acrolein, benzene and 1,3-butadiene were cited as relevant. A review of the levels of these chemicals and their subsequent levels of biomarker of exposure (Section 4 [of BAT’s response]) shows there is a clear reduction in the levels of these chemicals that users and bystanders will be exposed to with [BAT’s heated tobacco product] glo relative to cigarette smoke.
While BAT does not say what product FDA was talking about, the only similar product that FDA has issued an MRTP for is Philip Morris’ IQOS heated tobacco product in the USA. (So much for only considering EU data.) In addition, while FDA did find lower levels of some toxins in IQOS than a cigarette, it did not act on the fact that that IQOS produces higher levels of other toxins than a cigarette. FDA also refused Philip Morris’ request to claim that IQOS was safer than a cigarette.
BAT tries to explain away the strong evidence of a gateway effect for kids by invoking the “The common liability model, where inclination towards risk-taking and psychosocial processes can be factors, provides a parsimonious explanation of substance use co-occurrence.” This argument, which is just the latest incarnation of the “constitutional hypothesis” that the industry used to argue against the link between smoking and lung cancer half a century ago (there is a common gene that makes people smoke and also, independently, causes lung cancer), ignores the fact that almost all the studies of e-cigarettes’ gateway effect for smoking control for a range of social, behavioral, and demographic factors that predict smoking.
Finally, my favorite BAT complaint is that only 3% of the papers SCHEER cited were from the industry. The tobacco companies have a long history of manipulating their studies and presentation of results to get their desired outcomes. They have even helped create industry-friendly journals to publish their work, such as Regulatory Toxicology and Pharmacology, where many of the studies BAT cites were published.
Rather than a criticism, this is a great strength of the SCHEER opinion. Indeed, in their final report, SCHEER should only rely on information produced independently from the industry and its friends and supplicants.
May 11, 2021 update
The final report was published on April 16, 2021. It is available here.
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