Mimicking the human respiratory system: Online in vitro cell exposure for toxicity assessment of welding fume aerosol.

In assessing the biological impact of airborne particles in vitro, air-liquid interface (ALI) exposure chambers are increasingly preferred over classical submerged exposure techniques, albeit historically limited by their inability to deliver sufficient aerosolized dose. A novel ALI system, the Dosimetric Aerosol in Vitro Inhalation Device (DAVID), bioinspired by the human respiratory system, uses water-based condensation for highly efficient aerosol deposition to ALI cell culture. Here, welding fumes (well-studied and inherently toxic ultrafine particles) were used to assess the ability of DAVID to generate toxicological responses between differing welding conditions. After fume exposure, ALI-cultured cells showed reductions in viability that were both distinct between welding conditions and linearly dose-dependent with respect to exposure time; comparatively, submerged cell cultures ran in parallel did not show these trends across exposure levels. DAVID delivers a substantial dose in minutes (> 100 μg/cm), making it preferable over previous ALI systems, which require hours of exposure to deliver sufficient dose, and over submerged techniques, which lack comparable physiological relevance. DAVID has the potential to provide the most accurate assessment of in vitro toxicity yet from the perspectives of physiological relevance to the human respiratory system and efficiency in collecting ultrafine aerosol common to hazardous exposure conditions.