Poster, SOT 65th Annual Meeting and ToxExpo, March 22–25, 2026, in San Diego, California.
Michael Hollings, Adam Seymour, Emma Rothwell and Robert Bedford
Labcorp, Harrogate, UK
Introduction
Optimizing Respiratory NAMs for Acute Safety Assessment
In alignment with the FDA Modernization Act 2.0, the transition toward human-relevant, non-animal methodologies is essential for future drug and chemical safety evaluations. A recent study by Labcorp demonstrates how high-precision Air-Liquid Interface (ALI) models can be optimized to meet these rigorous regulatory standards. Using the VITROCELL® 24/4 exposure module, researchers evaluated acute 60-minute exposure scenarios for various gases, including Ethylene Oxide (EtO), Nitric Oxide (NO), and Sulphur Hexafluoride (SF6).
The results emphasize the importance of a multi-endpoint approach. While traditional viability assays (MTT/LDH) identified clear toxicological thresholds for certain gases, more sensitive measures like Transepithelial Electrical Resistance (TEER) and cytokine analysis revealed critical sub-lethal changes in barrier integrity and inflammatory signaling.
This research provides a robust foundation for identifying dose-dependent mechanistic responses, and ensures that in vitro respiratory models, such as the MucilAir tissue, deliver the reproducible and human-relevant data required for successful Investigational New Drug (IND) applications and broader regulatory screening
