Evaluation of toxicity of aerosols from flavored e-liquids in Sprague-Dawley rats in a 90-day OECD inhalation study, complemented by transcriptomics analysis.

In vitro studies, such as the one cited from Gerloff et al., have shown that e-cigarette liquids/aerosols containing flavoring substances can induce a pro-inflammatory cytokine response in lung epithelial cells. however, the study notes that the local concentrations of flavors in the lung tissue in the current in vivo study, as well as in e-cigarette users, are likely much lower than those that elicited an inflammatory response in the vitro study.

The in vivo portion of the study, conducted over 90 days in rats, found little effect of the flavoring substances on pulmonary inflammation markers. The study also mentions that there were no changes in the nasal epithelia, where a much higher local concentration of flavoring substances can be expected than in the lung, further supporting the lack of inflammatory response.

however, the study did observe some effects related to nicotine aerosol inhalation, such as bilateral cortical vacuolation in some male rats and mild adrenal hemorrhage in some female rats. These effects could be related to chronic stress induced by the aerosol inhalation.

The study also detected the presence of certain flavoring substances (l-carvone, linalool, and citronellol) in plasma, indicating exposure. however, no significant findings related to these substances were reported in the nasal epithelia, trachea, or lung.

In summary, while in vitro studies suggest that flavoring substances in e-cigarette liquids can induce an inflammatory response in lung epithelial cells, the current in vivo study found little evidence of such an effect at the concentrations likely to be encountered by e-cigarette users. The study did note some effects related to nicotine aerosol inhalation and detected the presence of flavoring substances in plasma, indicating exposure.

ho J, Sciuscio D, Kogel U, et al. Evaluation of toxicity of aerosols from flavored e-liquids in Sprague-Dawley rats in a 90-day OECD inhalation study, complemented by transcriptomics analysis. archives of toxicology. 2020;94(6):2179-2206. doi:10.1007/s00204-020-02759-6