Prototype e-cigarette and the capillary aerosol generator (CAG) comparison and qualification for use in subchronic inhalation exposure testing

Our objective was to evaluate the suitability of using a capillary aerosol generator (CAG) instead of using e-cigarette devices in 90-day or longer inhalation studies. Aerosol characteristics for both the CAG (which uses heat to produce a condensation aerosol) and e-cigarette generators have been previously reported, but a side-by-side comparison with the identical formulation has not been reported. Aerosols from both devices were analyzed immediately after generation for chemicals in the formulation (propylene glycol [PG], glycerin, water, and nicotine), selected carbonyls (acetaldehyde, acrolein, and formaldehyde) by ultra-performance liquid chromatography with ultraviolet detection (UPLC-UV), and a chemical fingerprint analysis using gas chromatography-mass spectroscopy (GC-MS). Aerosol capture methods for chemical analysis included Cambridge filter pads or two impingers in series each containing solution to trap and stabilize selected carbonyl compounds. Particle size distribution (cascade impactor) and exposure port uniformity (gravimetric) was measured in four rodent inhalation exposure chambers under inhalation study conditions. The aerosol of both generators contained the same known and unknown chemicals. Similar levels of compounds in the formula except for PG were detected in the aerosol of both generators. CAG produced more consistent particulate aerosol than e-cigarette generator and had lower levels of carbonyls primarily due to lower levels of formaldehyde. Exposure port concentrations were consistent and closer to target values with the CAG compared to the e-cigarette aerosol generator. CAG was easier to operate on a daily basis although more difficult to maintain because it required daily cleaning compared to single-use e-cigarettes. CAG was determined to be suitable for use in 90-day or longer inhalation studies.