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E-Cig Flavors Found to be Toxic When Inhaled

— June 22, 2018

E-Cig Flavors Found to be Toxic When Inhaled

Researchers examined the impact of nine flavorings commonly added to e-cigarettes, cigars, hookahs and other products and found that short-term exposure to these additives can be toxic to endothelial cell function.  This means, that flavorings could impair blood vessel function over time and lead to heart damage.  They impair nitric oxide production, which inhibits inflammation and clotting while regulating blood vessel enlargement in response to blood flow.

Vanillin (vanilla), cinnamaldehyde (cinnamon), eugenol (clove), and acetylpyridine (burnt flavor) impair A23187-induced nitric oxide production and increase expression of the proinflammatory mediator interleukin(IL)-6 across all concentrations tested, “suggesting that the endothelium is particularly sensitive to these flavors,” Jessica Fetterman, PhD, of Boston University School of Medicine, and her colleagues wrote of their findings.

There are more than 7,000 different flavors of e-cigarettes on the market.  Although many of the flavorings used have been determined to be safe in food products, the long-term safety for inhalation into the lungs is not yet known.

“When we eat something, the stomach has a lot of mechanisms to detoxify, but the lungs and blood vessels are largely unprotected,” Fetterman said. “People aren’t meant to inhale a lot of stuff into their lungs other than air.”

In addition to examining vanillin, cinnamaldehyde, eugenol, and acetylpyridine, the researchers also investigated the impact of dacetyl (butter), dimethylpyrazine (strawberry), isoamyl acetate (banana), and eucalyptol (spicy cooling) on endothelial cell function.  Isolated endothelial cells from participants who use non-menthol- or menthol-flavored tobacco cigarettes showed impaired A23187-stimulated nitric oxide production compared with those from nonsmokers.

Photo by John Caroro on Unsplash

Treatment of endothelial cells isolated from nonsmoking participants with either menthol (0.01 mmol/L) or eugenol (0.01 mmol/L) decreased A23187-stimulated nitric oxide production.

The researchers incubated commercially available human aortic endothelial cells with vanillin, menthol, cinnamaldehyde, eugenol, dimethylpyrazine, diacetyl, isoamyl acetate, eucalyptol, and acetylpyrazine (0.1–100 mmol/L) for 90 minutes.  They then measured cell death, reactive oxygen species production, expression of IL-6, and nitric oxide production.

“Cell death and reactive oxygen species production were induced only at high concentrations unlikely to be achieved in vivo.  Lower concentrations of selected flavors (vanillin, menthol, cinnamaldehyde, eugenol, and acetylpyridine) induced both inflammation and impaired A23187-stimulated nitric oxide production consistent with endothelial dysfunction,” according to the report.

Tobacco flavoring additives were found to restrict stimulated nitric oxide production and inflammation, “suggestive of endothelial dysfunction across a range of concentrations likely to be achieved in vivo.”

Fetterman said future studies are needed to better understand the short-term and long-term cardiovascular impact of exposure to inhaled tobacco product flavorings.  The limitations of their procedure included that flavoring compounds were suspended in media without heating or the addition of other typical electronic liquid constituents, such as the solvents propylene glycol and glycerol. “Heating or combustion of the flavoring compounds likely alters the compounds, making them more or less toxic.”

Still, the study findings overall “provide quantitative support for the regulatory prohibition or the establishment of limitations on allowable levels of these flavorings in electronic liquids and other tobacco products.”  The U.S. Food and Drug Administration is currently considering a ban on toxic flavors added to e-cigarettes and other tobacco products.


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