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Flavorants and Propylene Glycol From e-Cigarettes Form Harmful Irritants When Combined

The mixture of flavorants and propylene glycol (PG) in electronic cigarettes (e-cigs) leads to the formation of acetals that have been shown to activate irritation receptors, predisposing users to the same potential dangers as using traditional cigarettes, a new study said.

Many current smokers, especially the younger generation, have viewed e-cigs as the new vibe and an alternative for conventional cigarettes. One of the appeals that separates e-cigs from conventional cigarettes is the variety of flavors that users can enjoy. Flavors are created from “e-liquids” prepared from mixing the flavorants and nicotine in different ratios of PG and alcohol. Although the process of flavoring seems safe, the combination of aldehydes from the flavorants and alcohols from the e-liquid composition undergoes the formation of acetals that may have toxicological properties.

“Even in the absence of heating and combustion, chemical reactions are occurring in e-cigarette liquids and the resulting compounds could be harmful to the user’s airways,” said Hanno Erythropel, PhD, a postdoctoral associate in chemical and environmental engineering at Yale and a co-author of the study. To investigate the safety of e-cigs, investigators sought to analyze if acetals were made in e-liquid environments, whether they would remain stable after exposure, and if they would activate irritant receptors.

In this study, flavor aldehydes were mixed together with PG of different contents. In every flavoring aldehyde tested, including vanillin, ethylvanillin, benzaldehyde, cinnamaldehyde, acetals were produced. Investigators also observed increasing acetal production when PG contents were increased. These findings helped demonstrate a positive correlation between PG content and acetals. Investigators next examined whether acetals were deposited into airways after vaping. In this aspect, carryover rates between the flavor aldehydes and the acetals were very similar, approximating 50% to 80% of their respective concentrations.

Another end point that was examined was the potential airway irritation that acetals can cause. This endpoint was especially important; since acetals were not listed as an ingredient in e-cig labeling, their potential toxicity could redefine the hazards of e-cigs. Transient receptor potential (TRP) irritant receptor activation was used to measure if flavor aldehydes or acetals caused airway irritation. Results from this study revealed that both the flavoring aldehydes and the acetal products activated TRP. Furthermore, acetals also activated the vanilloid receptor, TRPV1, another potential contributor for airway irritation.

Flavoring agents are used in many foods and cosmetics. While the skin and the gut have numerous mechanisms to prevent harm, the airway is extremely fragile and especially provoked to inflammation and irritation. E-cigs have been recommended in many countries as a viable method for smokers to quit smoking conventional cigarettes.

However, e-cigs and “the long-term effects of these chemicals on the airways are unknown,” Erythropel said. Future risk assessments should be done to provide comprehensive data on the safety of e-cigs.


Erythropel HC, Jabba SV, DeWinter TM, et al. Formation of flavorant-propylene glycol adducts with novel toxicological properties in chemically unstable e-cigarette liquids [published online October 18, 2018]. Nicotine Tob Res. doi: 10.1093/ntr/nty192.

David Bai/AJMC