Extractable and Leachable Studies on Electronic Nicotine Delivery System (ENDS) Components and E‑liquid Containers

Electronic nicotine delivery system (ENDS) components and e-liquid containers may influence the chemical composition of inhaled aerosols, potentially impacting user exposure and the product's appropriateness for the protection of public health. Extractable and leachable (E&L) studies are crucial for identifying the chemicals that migrate to the e-liquids from the components and containers housing the e-liquids during storage and inform the potential ENDS risks to public health. There are few published ENDS E&L studies that provide limited information regarding the components and e-liquid containers. Thus, this study includes extractable testing followed by leachable testing that are designed to comprehensively examine and determine the chemicals that migrate to the e-liquid from closed ENDS components and e-liquid containers (low-density polyethylene (LDPE) bottles, polyethylene terephthalate (PET) bottles). Testing was conducted by Eurofins BioPharma Product Testing laboratory, a contract laboratory specializing in pharmaceutical extractable and leachable analyses. Semiquantitative and nontargeted analyses were conducted using gas chromatography-mass spectrometry (GC-MS) for volatile compounds and ultra-high-performance liquid chromatography-photo diode array-mass spectrometry (UPLC-PDA-MS) for semi- and nonvolatile compounds. Semiquantitative and targeted analyses were conducted using GC-MS-selected ion monitoring (GC-MS-SIM) for polycyclic aromatic hydrocarbons (PAHs) and inductively coupled plasma MS (ICP-MS) for metals. All relevant peaks were tentatively identified using mass spectral libraries and identification criteria. Across all 47 products examined in the extractable study, 19 unique (i.e., distinct, identified compounds after removing duplicates) and 101 unknown semi- and nonvolatile compounds, 1591 unique and 18 unknown volatile compounds, 9 unique PAHs, and 12 unique metals were observed. The five products from each product type with the highest number and concentration of extractables above the preestablished thresholds across all four analytical methods were examined in the leachable study. Closed ENDS had the greatest number of leachables (243 compounds), while LDPE and PET bottles had comparable numbers of leachables (53-65 compounds). In summary, this study details a comprehensive E&L analysis and peak identification approach for ENDS. These findings demonstrate that established pharmaceutical E&L methodology can be applied to ENDS components and e-liquid containers, and certain methodological parameters (e.g., selection of solvents and libraries) may need to be optimized for ENDS products.