by Carl V Phillips

[UPDATE 4, 11 Jun 15: A correction to one of the results in the study has been posted to this blog by the author. As of yet, the journal has not posted the correction as requested.]

[UPDATE 3: The published version of the paper, at BMC Public Health, is now here.]

[UPDATE: Here is CASAA’s press release about this.]

[UPDATE 2: Here is the post of the press release at CASAA’s main blog (same content as above link, but with a link to here for discussion — so a better choice if you want to share the press release).]

CASAA is delighted to announce that the first research study funded by the CASAA Research Fund (thanks to all of you who donated to that!) has been released. The study, by Prof. Igor Burstyn, Drexel University School of Public Health, is available at the Drexel website, here (pdf). Burstyn reviewed all of the available chemistry on e-cigarette vapor and liquid and found that the levels reported — even in those studies that were hyped as showing there is a danger — are well below the level that is of concern.

And that assessment applies to the vaper himself. The exposure to bystanders is orders of magnitude less and of no concern at all.

The paper is technical, of course, but I believe it does a great job of communicating for readers at many levels. It puts the results in very clear and useful terms — exactly what policy makers need for making decisions.

For the first time, we have a definitive study that can be used to respond to claims that contaminants in e-cigarettes are dangerous and that there is a hazard to bystanders that calls for usage restrictions. Existing individual chemistry studies have been difficult for anyone other than an expert to understand (which is why we gave a grant to an expert to understand them!), and a naive interpretation of individual studies (just reading what the authors editorialized about their results) gave the impression of “dueling studies”, with some showing a problem and some not. While many THR advocates made an effort to make sense of and use the existing literature, it was almost impossible to do so effectively. Burstyn’s analysis solves that problem and shows there is no duel: All of the studies, including the “bad” ones, show that there is no worry.

I cannot overstate it: This is a game-changer for anyone trying to respond to misinformation about the hazards of e-cigarettes. Before we had an apparently contradictory mess on this topic. Now we have clarity.

I have to say that I am genuinely surprised that the results are quite so definitive, and I assume that will be true of anyone else of was seriously trying to assess the risks, rather than just cheerleading. We were all confident that the risks were minimal, but we could not previously reach a (good news) conclusion as strong as the one in the paper.

The list of key conclusions in the paper:

Even when compared to workplace standards for involuntary exposures, and using several conservative (erring on the side of caution) assumptions, the exposures from using e-cigarettes fall well below the threshold for concern for compounds with known toxicity. That is, even ignoring the benefits of e-cigarette use and the fact that the exposure is actively chosen, and even comparing to the levels that are considered unacceptable to people who are not benefiting from the exposure and do not want it, the exposures would not generate concern or call for remedial action.

Expressed concerns about nicotine only apply to vapers who do not wish to consume it; a voluntary (indeed, intentional) exposure is very different from a contaminant.

There is no serious concern about the contaminants such as volatile organic compounds (formaldehyde, acrolein, etc.) in the liquid or produced by heating. While these contaminants are present, they have been detected at problematic levels only in a few studies that apparently were based on unrealistic levels of heating.

The frequently stated concern about contamination of the liquid by a nontrivial quantity of ethylene glycol or diethylene glycol remains based on a single sample of an early technology product (and even this did not rise to the level of health concern) and has not been replicated.

Tobacco-specific nitrosamines (TSNA) are present in trace quantities and pose no more (likely much less) threat to health than TSNAs from modern smokeless tobacco products, which cause no measurable risk for cancer.

Contamination by metals is shown to be at similarly trivial levels that pose no health risk, and the alarmist claims about such contamination are based on unrealistic assumptions about the molecular form of these elements.

The existing literature tends to overestimate the exposures and exaggerate their implications. This is partially due to rhetoric, but also results from technical features. The most important is confusion of the concentration in aerosol, which on its own tells us little about risk to heath, with the relevant and much smaller total exposure to compounds in the aerosol averaged across all air inhaled in the course of a day. There is also clear bias in previous reports in favor of isolated instances of highest level of chemical detected across multiple studies, such that average exposure that can be calculated are higher than true value because they are “missing” all true zeros.

Routine monitoring of liquid chemistry is easier and cheaper than assessment of aerosols. Combined with an understanding of how the chemistry of the liquid affects the chemistry of the aerosol and insights into behavior of vapers, this can serve as a useful tool to ensure the safety of e-cigarettes.

The only unintentional exposures (i.e., not the nicotine) that seem to rise to the level that they are worth further research are the carrier chemicals themselves, propylene glycol and glycerin. This exposure is not known to cause health problems, but the magnitude of the exposure is novel and thus is at the levels for concern based on the lack of reassuring data.

It is worth expanding on the observation about propylene glycol and glycerin a bit: While there is no affirmative reason to believe that the level of exposure experienced by vapers is hazardous, we have never before had a situation where millions of people had such a high level of exposure. Thus it is worth gathering data on what happens, just to make sure there is no small subtle effect. This contrasts with the levels of the much-hyped contaminants, which pose no concern at all. It is also important to remember that this refers to the vaper herself; there is no such caution for bystanders, who have far far lower levels of exposure.

This paper should immediately become a central point in all political advocacy to stop anti-e-cigarette regulations, as well as trying to encourage smokers to adopt THR. The key talking point that should be used is this (my words, not Burstyn’s):

The only expert review of all of the studies found that there was no risk from the chemicals to vapers, let alone bystanders. This took into consideration the studies that you are referring to [note: assuming this is being used as a rebuttal to some claim of chemical hazards]. Indeed, even the results of the studies that have been used to generate alarm represented levels of chemicals that were too low to be of concern.

For those of you who have any comments for the author, particularly peer review (or even non-peer review) comments for improving on the working paper before it is submitted to a journal[*], please use the comments section of this post. The author has agreed to monitor one page (this one), but will probably not see it if you post a comment at another blog, on ECF, etc.

[*Footnote: To head off a concern I have heard a few times, no, there is not a problem with the author releasing a working paper before submitting to a journal. A handful of medical and general-science journals — those that are trying to sell copies as if they were a glossy magazine — like to have “exclusives” of previously secret studies (which, by the way, is why they publish far more papers that are shown to be wrong than do more serious journals). Serious science journals generally prefer that the paper is circulated and commented on before they are asked to deal with it. Indeed, in several of the more serious sciences (public health will catch up in a few decades — perhaps), working paper versions are considered the key source of scientific communication, and the eventual appearance in a journal is more of an afterthought and happens long after everyone has already read the paper. Real peer review is what starts now (here) when every interested expert can read and comment, rather than at a journal where a couple of people with their limited knowledge are the only ones reviewing it.

[Of course, that knowledge does not help you if you are dealing with people who do not understand how science works and are not likely to listen long enough to learn. There will be retorts of “that is not a peer-reviewed publication” (which is actually not true — it was reviewed before the author released it). Your best talking point in response to that is something like, “So are you saying that in a few months, when the paper appears in a journal, you will agree that it is all correct and change your position?” If you are responding to someone who claims to be an expert, you can add “So, why don’t you just review it like other expert readers have done, or are you admitting that you are not expert enough to do so?”

[UPDATE 3 vers.2: Later posts here that relate to this study can be found at this tag.]