Diacetyl and other flavored molecules have been targeted by researchers who discovered relative innocuousness upon ingestion but a potentially strong harmfulness when inhaled. The first cases were described in food factories where Diacetyl was used as a flavor for popcorns and cases were further described in other sectors.
With more than 7,000 varieties of flavors marketed in the USA and the increasing popularity of the e-cigarette using those liquids, the Assistant Professor of exposure assessment science and first author of this publication stresses the emergency of the situation, in the absence of current regulation.
The U.S. Food and Drug Administration (FDA) has issued a proposed rule to include vaping products under its authority to regulate certain tobacco and nicotine-containing products but the official publication of this bill is not expected before January 1, 2016 for an implementation expected in early 2016. The absence of legal frame may be at the origin of class actions against manufacturers: The e-liquid manufacturer Five Pawns has already been subject to suing by class action for deliberate use of the Diacetyl and Acetylpropionyl in the receipts of its e-liquids.
In an interview for the Harvard Gazette, after the publication of their paper, the J. Allen adds that the flavored liquids are very popular among the youngest vapers who would be the most affected population. The U.S. Food and Drug Administration (FDA) has issued a proposed rule to include e-cigarettes under its authority to regulate certain tobacco and nicotine-containing products and its publication is expected after January 1, 2016. According to figures, the e-cigarette is mainly associated to smoking cessation in a population of smokers and their use by never-smokers is scarce. The young population who “tries it” generally do not stick to their use on the long-term and studies confirm that it should not be considered as a gateway to tobacco, either in France or in Europe and probably also in the USA.
Dr K. Farsalinos, whose study was cited by his Harvard colleagues, judges that the article is “creating false impressions and exaggerates the potential risk from Diacetyl and Acetylpropionyl exposure through e-cigarettes”. Farsalinos’ comments address two points:
- Allen et al. failed to mention the presence of these compounds in tobacco smoke it creates the false impression that it is a new hazard ;
- The levels shown by Allen et al. are in the lower range of the values he found himself in his samples. Another aspect of the discussion is the controversial use of NIOSH safety limits that address the tolerable concentration of volatile organic compounds in working environments.
The controversy comes from the fact that the population considered for the use of NIOSH safety limits is supposed to be the most vulnerable people in a general population of never-smokers. This of course does not apply to vapers who are former smokers.
Update on 6/07/2016:
The “popcorn lung” debate
In reaction to J. Allen’s article, Jennifer Pierce and her co-authors commented  and vigorously criticized the way their colleagues presented the problem raised by the presence of Diacetyl, Acetylpropionyl and Acetoin in e-liquids.
They pointed out that such airborne diketone levels above the NIOSH and ACGIH OELs are not necessarily indicative of respiratory risk. No “popcorn lung” has been shown to be associated to unflavored coffee beans, even if these grains are naturally rich in such compounds.
A second point addressed by the scientists is that naturally occurring Diacetyl and Acetylpropionyl were measured at higher levels in cigarette smoke. Hence, switching from smoking to vaping decreases exposure to these compounds, and corresponds to a lowering of the respiratory risk, which is not straightforward when reading Allen et al.’s manuscript.
To finish, the authors recall that “the causal relationship between diacetyl exposure and development of bronchiolitis obliterans has not been firmly established” (OSHA 2016), which leaves open the debate of an increased risk of diketone-related “popcorn lung” or any other serious respiratory disease in flavorings-exposed workers and, hence, vapers.
Allen et al.  counteract Pierce et al.‘s comments not only on their arguments, bargaining on statistics, but also on their publications and especially on the suspicious way two of them underwent peer-review within only three days.
The counterattack ends on the risk for the children who are trying e-cigarettes without smoking for whom the exposition is not decreasing. Allen et al. quote the 160,000 US kids, non-smokers, who are particularly appealed by the sweetest flavors like cupcake and cotton candy. Therefore, they recommend “to evaluate this potential hazard further, restrict access by youth, and provide consumers with information and warnings similar to those given to workers“.
Considering that such vaping products are intended to adults above 18 of age (as imposed by the law) and their access theoretically forbidden to minors, such recommendation made by Allen et al. seems irrelevant.
Some standards are already in place
Current MHRA guidance documents that have been elaborated by the UK bans Diacetyl and Acetylpropionyl (or pentane 2,3 dione) from e-liquids in its draft version, so does the AFNOR standard XP D90-300-2 for diacetyl. The institute declared to be ready to deliver certifications for e-liquids that complies with the new regulation.
 Allen JG, Flanigan SS, LeBlanc M, Vallarino J, MacNaughton P, Stewart JH, Christiani DC. 2015. 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; http://dx.doi.org/10.1289/ehp.1510185
 Pierce JS., Abelmann A., Finley BL. 2016. Comment on “Flavoring Chemicals in E-Cigarettes: Diacetyl, 2,3-Pentanedione, and Acetoin in a Sample of 51 Products, Including Fruit-, Candy-, and CocktailFlavored E-Cigarettes”. Environ Health Perspect; DOI:10.1289/ehp.1611350
 Allen JG, Flanigan SS, LeBlanc M, Vallarino J, MacNaughton P, Stewart JH, Christiani DC. 2016. Response to “Comment on “Flavoring Chemicals in E-Cigarettes: Diacetyl, 2,3-Pentanedione, and Acetoin in a Sample of 51 Products, Including Fruit-, Candy-, and CocktailFlavored E-Cigarettes” Environ Health Perspect; DOI:10.1289/EHP348