Many scientific papers have documented the harmful effects of vaping and some chemicals in e-liquids, but few go so far as to name names. A paper released in March in Chemical Research in Toxicology pulls no punches. It calls out Juul’s e-liquid formulation, arguing that the combination of nicotine and flavoring chemicals in the pods are a “cause for concern,” even compared to other vape manufacturers.
Juul has been called out before for advertising to teens. But this study, led by Prue Talbot, Ph.D., director of the University of California Riverside’s Stem Cell Center, is dedicated to two of the 59 chemicals they quantified in their sample of Juul pods: nicotine and ethyl maltol, a sweet flavoring ingredient that was present in three of the pods studied. Talbot and her co-authors found that both concentrations of nicotine and concentrations of ethyl maltol were so high they had toxic effects on human lung cells.
“Our studies indicate that a better understanding of Juul products is needed,” she tells Inverse. “The nicotine concentrations are excessively high, and this could be addressed by regulatory agencies.”
In a statement to Inverse, Juul’s representatives questioned the scientific techniques used in this analysis.
We believe this study has significant limitations, including the use of flawed methodologies. We are assessing the results of this study in more detail. At JUUL Labs, we are committed to the highest quality of scientific research and analysis as we pursue our mission of eliminating cigarettes.
It’s clear from Talbot’s research why Juul would be concerned.
Three Times the Nicotine
Talbot’s findings focused on eight different flavors of Juul pods: cool mint, brulee, mango, fruit medley, Virginia tobacco, cool cucumber, classic menthol, and classic tobacco. All of these flavors contain nicotine (they were Juul’s five percent pods, though Juul also sells three percent nicotine pods), but ethyl maltol was only a major component of mango, créme brulee, and Virginia tobacco pods (though the latter had far less ethyl maltol than the former two).
Juul advertises a “vapor experience like no other,” and that’s exactly what Talbot found. When she compared Juul pod nicotine concentrations to that of 34 competing brands, she found that Juul pods had up to three times as much nicotine per milliliter.
What Nicotine Does to Cells
To see the effect of such high nicotine concentrations, Talbot exposed human bronchial epithelial cells (a type of lung cell) to vaporized fluid in a dish and watched for changes associated with the functioning of the mitochondria, the parts of the cell that manufacture energy. All pod fluids were considered cytotoxic in two of the three established tests they used — that is, they “produced an effect that was 30% less than the untreated control.”
These changes, she explains, were correlated with the high concentrations of nicotine, suggesting that the nicotine itself drove the change. “The concentration of nicotine in Juul pods,” she says, “is high enough to be a concern.”
Talbot noticed the same cytotoxic effects on enzymes in the flavors with significant ethyl glycol concentrations present in the mango, créme brulee, and Virginia tobacco flavors. Nicotine was still the major component in these pods, but they also had a lot of ethyl glycol, which has been proven to be cytotoxic in her earlier papers.
“Ethyl maltol, which was present in three flavors of pods, was also cytotoxic in both of our assays and cytotoxicity correlated with ethyl maltol concentration,” she says. “Therefore, even though the concentrations of ethyl maltol in 3 JUUL pods were well below those of nicotine, ethyl maltol was present in some pods at concentrations that would be cytotoxic.”
It’s still unclear exactly how these toxic effects play out in living human airways. One study has shown that using vapes in general — not just Juul products — is associated with wheezing. Though that study looked at different chemicals present in e-liquids, not specifically the influence of nicotine and ethyl maltol.
While the overall picture painted in this analysis may not bode well for Juul, it’s still not time for other companies to rest easy given the other effects of e-liquids that have been uncovered. Even the executives of competing vape manufacturer blu, fresh off the completion of a giant model Earth in downtown New York, shouldn’t be too enthused by the results.
Abstract: While JUUL electronic cigarettes (ECs) have captured the majority of the EC market with a large fraction of their sales going to adolescents, little is known about their cytotoxicity and potential effects on health. The purpose of this study was to determine flavor chemical and nicotine concentrations in the eight currently marketed pre-filled JUUL EC cartridges (“pods”) and to evaluate the cytotoxicity of the different variants (e.g., “Cool Mint” and “Crème Brulee”) using in vitro assays. Nicotine and flavor chemicals were analyzed using gas chromatography-mass spectrometry in pod fluid before and after vaping and in the corresponding aerosols. 59 flavor chemicals were identified in JUUL pod fluids, and three were >1 mg/mL. Duplicate pods were similar in flavor chemical composition and concentration. Nicotine concentrations (average 60.9 mg/mL) were significantly higher than any EC products we have analyzed previously. Transfer efficiency of individual flavor chemicals that were >1 mg/mL and nicotine from the pod fluid into aerosols was generally 35 - 80%. All pod fluids were cytotoxic at a 1:10 dilution (10%) in the MTT and neutral red uptake assays when tested with BEAS-2B lung epithelial cells. Most aerosols were cytotoxic in these assays at concentrations between 0.2 and 1.8%. The cytotoxicity of collected aerosol materials was highly correlated with nicotine and ethyl maltol concentrations and moderately to weakly correlated with total flavor chemical concentration and menthol concentration. Our study demonstrates that: (1) some JUUL flavor pods have sufficiently high concentrations of flavor chemicals that may make them attractive to youth, and (2) the concentrations of nicotine and some flavor chemicals (e.g. ethyl maltol) are high enough to be cytotoxic in acute in vitro assays, emphasizing the need to determine if JUUL products will lead to adverse health effects with chronic use.