This is where the science gets concerning. While the base ingredients of e-liquid (PG, VG, nicotine) are relatively well-studied, flavoring chemicals are a different story. There are thousands of flavoring compounds used in e-liquids, and most have never been tested for inhalation safety.
The Most Studied (and Most Concerning) Flavorings
| Flavor Chemical | Flavor Profile | Known Lung Risk | Evidence Level |
|---|---|---|---|
| Diacetyl | Buttery, creamy | Causes bronchiolitis obliterans ("popcorn lung") in high-dose occupational settings | Moderate — animal data + occupational data, no confirmed vaping cases |
| Cinnamaldehyde | Cinnamon | Strong cytotoxicity in lung cell studies; impairs immune function in airways | Moderate-High — consistent cell study findings |
| 2,3-pentanedione | Buttery (diacetyl substitute) | Similar to diacetyl but less studied; used as "safe" replacement | Low-Moderate — limited data |
| Sucralose | Sweet | Thermal degradation produces chlorinated compounds; catalyst effect on coil | Moderate — emerging concern, not definitive |
| Menthol | Mint, cool | Mild cooling effect on airways; TRPM8 receptor activation | Low — generally considered lower risk |
Cinnamaldehyde is worth highlighting. Multiple studies — including work from the Christen lab at the University of Rochester — have shown that cinnamon-flavored e-liquids produce consistently high levels of cytotoxicity in lung epithelial cells. Cinnamon is one of the most popular flavor categories, and many vapers use it daily without knowing about these findings.
For a more detailed breakdown of flavoring toxicity and other ingredient concerns, our complete e-liquid ingredients guide covers PG/VG thermal decomposition, heavy metals, and the full list of high-risk flavorings.
The FDA's flavored ENDS PMTA draft guidance (March 2026) creates a two-tier risk system that partly addresses these concerns — fruit, candy, and dessert flavors face a higher evidentiary bar than menthol, mint, and tobacco flavors. But the draft guidance has been criticized by public health groups for still allowing menthol, which has its own set of concerns related to addiction and youth initiation.
