Comparative In Vitro Toxicity of ENDS Aerosols: Impact on Macrophages

As the popularity of electronic nicotine delivery system (ENDS) devices continues to rise, there is a growing need to understand their potential health effects, particularly on immune cells. In a recent study by Drs. Pinkston, Penn and Noel (2023), researchers investigated the comparative in vitro toxicity of ENDS aerosols, focusing on the impact on macrophages. This study specifically examined the effects of Menthol and Crème Brûlée-flavored aerosols generated from both 3rd and 4th-generation ENDS devices. The findings shed light on the potential immunological harm associated with these aerosols and the role of nicotine salt-based ENDS products.

The researchers employed a physiologically-relevant in vitro air-liquid interface (ALI) exposure model using the inExpose system to assess the toxicity of different ENDS devices. Murine macrophages (RAW 264.7) were exposed to air, Menthol, or Crème Brûlée-flavored ENDS aerosols for 1 hour per day, over 1 or 3 consecutive days. Aerosol generation was conducted following established protocols, and the collected aerosols were subjected to chemical analysis to determine the levels of nicotine, solvents, and carbonyl compounds.

The study revealed significant cytotoxicity and changes in lactate dehydrogenase (LDH), reactive oxygen species (ROS), nitric oxide (NO), and oxidative stress markers in macrophages exposed to Menthol and Crème Brûlée-flavored aerosols from both 3rd and 4th-generation ENDS devices. Notably, Crème Brûlée-flavored aerosols induced higher cytotoxicity than the Menthol flavor. Additionally, nicotine salt-based aerosols were found to contribute to the differential effects observed between the two generations of ENDS devices.

The findings of this study highlight the detrimental effects of Menthol and Crème Brûlée-flavored aerosols on macrophages. The comparison between 3rd and 4th-generation ENDS devices indicates that the complexity of flavoring mixtures, such as Crème Brûlée, composed of multiple flavoring chemicals, may contribute to increased cellular toxicity. Moreover, the presence of high levels of nicotine salts and solvents in certain ENDS products, such as the 4th-generation disposable devices, further exacerbates the physiological responses observed in macrophages.