Flavorings are the most complex and least transparent ingredient category. A single e-liquid may contain dozens of flavoring molecules, and manufacturers typically list them under general category names ("natural and artificial flavors") rather than identifying specific chemical compounds. This creates a significant consumer information gap.
The Most Studied Flavoring Chemicals
Diacetyl (2,3-butanedione)
A butter-flavoring chemical detected in some e-liquids. High doses of inhaled diacetyl can cause bronchiolitis obliterans — "popcorn lung" — a condition where the bronchioles become permanently inflamed and scarred. The condition was first identified in workers at microwave popcorn factories. A CDC study evaluated flavoring-related lung disease risk at six microwave popcorn plants and found workers were affected at five plants, with mixing-area exposure to diacetyl as low as 0.02 ppm causing damage. While no confirmed cases of popcorn lung have been directly attributed to vaping, the presence of diacetyl in some e-liquids remains a concern.
Acetyl Propionyl (2,3-pentanedione)
A diacetyl substitute that has been associated with airway fibrosis in rats. The risks associated with 2,3-pentanedione inhalation are comparable to diacetyl in rat studies. NIOSH proposed an upper limit for time-weighted average exposure of 9.3 ppb (38 μg/m³).
Cinnamaldehyde
The primary flavoring compound in cinnamon-flavored e-liquids. A 2022 systematic review by Effah et al. found that cinnamon, strawberry, and menthol flavors showed greater detrimental effects in vitro than other flavors, with perturbations of pro-inflammatory biomarkers and enhanced cytotoxicity being the most commonly reported effects.
Vanillin and Sucralose: The Catalyst Problem
Vanillin (commonly used in dessert flavors) and sucralose (a sweetener) present a less obvious but serious risk: they can catalyze the thermal degradation of PG and VG. A 2025 study by Page et al. in ACS Omega found that flavoring compounds such as triacetin and sucralose can catalyze thermal degradation, resulting in significantly greater yields of hazardous carbonyls including formaldehyde, acetaldehyde, and acrolein. A 2022 study found that vaporization of sucralose-containing e-liquid increased production of aldehydes and also produced chloropropanols — chlorinated compounds with no safe exposure level.
Limitations of Current Flavoring Research
Most flavoring toxicity studies use in vitro cell culture models (A549 lung epithelial cells, bronchial epithelial models) rather than human clinical trials. In vitro results indicate potential harm but cannot directly predict real-world disease outcomes in living humans. The sheer number of flavoring compounds — hundreds are used across the industry — means most have never been individually tested for inhalation toxicity. Additionally, flavoring molecules can interact with each other and with PG/VG during heating, creating new compounds that were not present in the original liquid.
