An evaluation of electronic cigarette formulations and aerosols for harmful and potentially harmful constituents (HPHCs) typically derived from combustion

U.S. FDA draft guidance recommends reporting quantities of designated harmful and potentially harmful constituents (HPHCs) in e-cigarette e-liquids and aerosols. The HPHC list comprises potential matrix-related compounds, flavors, nicotine, tobacco-related impurities, leachables, thermal degradation products, and combustion-related compounds. E-cigarettes contain trace levels of many of these constituents due to tobacco-derived nicotine and thermal degradation. However, combustion-related HPHCs are not likely to be found due to the relatively low operating temperatures of most e-cigarettes. The purpose of this work was to use highly sensitive, selective, and validated analytical methods to determine if these combustion-related HPHCs (three aromatic amines, five volatile organic compounds, and the polycyclic aromatic hydrocarbon benzo[a]pyrene) are detectable in commercial refill e-liquids, reference e-cigarette e-liquids, and aerosols generated from rechargeable e-cigarettes with disposable cartridges (often referred to as “cig-a-likes”). In addition, the transfer efficiency of these constituents from e-liquid to aerosol was evaluated when these HPHCs were added to the e-liquids prior to aerosol formation. This work demonstrates that combustion-related HPHCs are not present at measurable levels in the commercial and reference e-liquids or e-cigarette aerosols tested. Additionally, when combustion-related HPHCs are added to the e-liquids, they transfer to the aerosol with transfer efficiencies ranging from 49% to 99%.