Chemical adducts of Reactive Flavor aldehydes Formed in E-Cigarette Liquids are Cytotoxic and Inhibit Mitochondrial Function in Respiratory Epithelial Cells.

Introduction:
This summary will discuss a study examining the cytotoxic and metabolic effects of chemical adducts formed in e-cigarette liquids between flavor aldehydes and solvent chemicals. The study compares the toxicological properties of these chemical adducts with their parent flavor aldehydes and suggests that they may contribute to the health effects of e-cigarette aerosol in the respiratory system of e-cigarette users.

Key Points:

* The study found that chemical adducts formed in e-cigarette liquids between flavor aldehydes and solvent chemicals, named flavor aldehyde PG/VG acetals, can efficiently transfer to e-cigarette aerosol.
* The study compared the cytotoxic and metabolic toxic effects of acetals and their parent aldehydes in respiratory epithelial cells.
* The study used cell metabolic assays, LIVE/DEaD cell assay, and Click-iT EDU cell proliferation assay to analyze the effects of benzaldehyde, vanillin, and their corresponding PG acetals on bronchial (BEaS-2B) and alveolar (a549) epithelial cells.
* The study found that PG acetals reduced key parameters of cellular energy metabolic functions, including basal respiration, aTP production, and spare respiratory capacity.
* PG acetals were more cytotoxic than their parent aldehydes, with benzaldehyde PG acetal increasing cell mortality in BEaS-2B and hNEpC, and vanillin PG acetal being more cytotoxic than vanillin at the highest concentration tested.
* Both vanillin and vanillin PG acetal reduced cellular proliferation in a concentration-dependent manner.
* The study suggests that manufacturers' disclosure of e-liquid ingredients at time of production may be insufficient to inform a comprehensive risk assessment of e-liquids and electronic nicotine delivery systems use due to the chemical instability of e-liquids over time and the formation of new compounds.

Main Message:
The study highlights the need for further toxicological studies on chemical adducts formed in e-cigarette liquids, as they have differential toxicological properties from their parent flavor aldehydes and may contribute to the health effects of e-cigarette aerosol in the respiratory system of e-cigarette users. The study suggests that regulations requiring manufacturers' disclosure of e-liquid ingredients at time of production may be insufficient to inform a comprehensive risk assessment of e-liquids and electronic nicotine delivery systems use due to the chemical instability of e-liquids over time and the formation of new compounds.

Jabba SV, Diaz aN, Erythropel hC, Zimmerman JB, Jordt SE. Chemical adducts of Reactive Flavor aldehydes Formed in E-Cigarette Liquids are Cytotoxic and Inhibit Mitochondrial Function in Respiratory Epithelial Cells. Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco. 2020;22:S25-S34. doi:10.1093/ntr/ntaa185