Human in vitro airway models to assess point-of-contact respiratory toxicity of surfactants and derive human equivalent concentrations after single dose exposure.

Surfactants are widely used in products such as soaps, adhesives, and agrochemical formulations where they function as emulsifiers, wetting agents, detergents, foaming agents, or dispersants. Despite the potential for inhalation exposure, human-relevant hazard data are limited. Surfactants can interact with amphiphilic cell membranes, compromising membrane integrity and leading to cytotoxicity. To assess point-of-contact respiratory tissue irritation potential of these chemicals, a human bronchial epithelial cell line (BEAS-2B) and a reconstructed human respiratory epithelial (RHRE; MucilAir) model were exposed to two surfactants-oleoyl sarcosine or Triton X-100 as aerosols (BEAS-2B cells only) or liquids (in both systems). Aerosol exposures were not further pursued due to similar trends in results as liquid exposures and the need for further technical optimization. Cells were exposed for 24 hours to 30 µL (91 µL/cm²) of either surfactant at five concentrations. Cellular effects were assessed after 24 hours of exposure in BEAS-2B cells and MucilAir, and at 7 days after the start of exposure in MucilAir only. Generally, dose-dependent effects were observed for both surfactants within each cell system. Oleoyl sarcosine was more toxic in BEAS-2B cells compared to Triton X-100, and no clear difference in toxicity between the two surfactants was observed in MucilAir. Benchmark Dose (BMD) and Multiple-Path Particle Dosimetry (MPPD) modeling were performed to translate in vitro data to human equivalent concentrations (HECs). This manuscript demonstrates the application of an in vitro test method and in vitro to in vivo extrapolation (IVIVE) to predict point-of-contact respiratory tissue irritation in humans.