Two- and Three-Dimensional Culture Systems: Respiratory In Vitro Tissue Models for Chemical Screening and Risk-Based Decision Making

Risk of lung damage from inhaled chemicals or substances has long been assessed using animal models. However, New Approach Methodologies (NAMs) that replace, reduce, and/or refine the use of animals in safety testing such as 2D and 3D cultures are increasingly being used to understand human-relevant toxicity responses and for the assessment of hazard identification. Here we review 2D and 3D lung models in terms of their application for inhalation toxicity assessment. We highlight a key case study for the Organization for Economic Cooperation and Development (OECD), in which a 3D model was used to assess human toxicity and replace the requirement for a 90-day inhalation toxicity study in rats. Finally, we consider the regulatory guidelines for the application of NAMs and potential use of different lung models for aerosol toxicity studies depending on the regulatory requirement/context of use.

EpiAirway (AR-100, EpiAlveolar ALV-100-FT-PE12, MucilAir, NHBE 2D monolayer cultures, cell lines, Calu-3, BEAS-2B, A549, 16HBE14o, Met-5A, organoids, spheroids, multi-organ on a chip particles, MOC, In Vitro-to-In Vivo Exposures Dosimetry, IVIVE, OECD test guideline, regulatory acceptance