Heating Coil Corrosion by E-Liquid Containing Nicotine Lactate Salt and In Vitro and In Vivo Evaluation of Nickel Leachate in E-Liquid and E-Cigarette Aerosol

Nicotine lactate salt is one of the commonly used nicotine salts in electronic cigarette (e-cigarette) formulations, including products that have received Marketing Granted Orders through the FDA's Premarket Tobacco Product Application (PMTA) evaluation in the US. However, full-life cycle evaluation on nicotine lactate salt remains limited, especially its leaching reactions with heating elements and the potential to influence aerosol composition. This study investigated the chemical effects of nicotine lactate salt on e-cigarette heating coils and potential toxicological consequences of nickel (Ni) leachates using in vitro cells and animal models. The results showed that immersion of heating coils in e-liquid (PG:VG 6:4) containing 2% nicotine lactate salt resulted in a significant increase in Ni concentration in the e-liquid over a period of 4 weeks, with levels rising over time as compared to the nicotine benzoate group. A commercially available disposable e-cigarette (liquid capacity: 9.4 mL; power output: 11 W) was utilized. Similarly, aerosol generated from the e-liquid containing 2% nicotine lactate salt exhibited elevated Ni levels. In vitro cytotoxicity exposure to the Beas-2B, SH-SY5Y, and HepG2 cell lines indicated that the aerosol generated from 2% nicotine lactate e-liquid showed higher toxicity than that of the 2% nicotine benzoate e-liquid, with more pronounced Ni accumulation in cells. In vivo inhalation using C57BL/6J mice demonstrated significant Ni accumulation in mice exposed to the aerosol produced from nicotine lactate salt, particularly in the liver. The corrosion of heating coils of nicotine lactate salt e-liquid was attributed to combined electrochemical and acidic corrosion mechanisms. In conclusion, our findings provide valuable insights into the material compatibility and potential toxicological implications for nicotine lactate-based e-liquids in electronic nicotine delivery systems. More research is needed to fully assess the implications of these preclinical findings.