Coolant Flavors Exacerbate Nicotine Effects in Craniofacial Cells

Area of Science:

• Toxicology
• Cell Biology
• Public Health

Background:

• Electronic Nicotine Delivery Systems (ENDS) pose public health risks, with flavors appealing to non-smokers.
• Industry shifts to "copy-cat" coolants to circumvent flavor regulations.
• Prior research indicated vape components harm craniofacial cells.

Purpose of the Study:

• To investigate the in vitro effects of coolant formulations, including synthetic analogs, on craniofacial-derived cells.
• To compare the toxicological profiles of menthol, WS3, and WS23, with and without nicotine, propylene glycol (PG), and glycerin (G).

Main Methods:

• Assessed cell viability, apoptosis, autophagy, and senescence in murine craniofacial-derived cells.
• Exposed cells to ENDS constituents: nicotine, PG, G, menthol, WS3, and WS23, individually and in combination.

Main Results:

• Menthol, WS3, and WS23 exhibited similar toxicological profiles regarding cell viability.
• Combinations of coolants with nicotine and PG/G further reduced cell viability.
• Senescence was observed only for menthol when combined with PG/G and/or nicotine; apoptosis and autophagy remained unchanged.

Conclusions:

• Synthetic coolants WS3 and WS23 mimic menthol's effects on craniofacial cells under acute exposure.
• Safety evaluations for ENDS must include menthol-like coolants and their analogs.
• Findings support incorporating coolant flavorants into regulatory toxicology and hazard screening, especially for youth-targeted products.