High-throughput screening of respiratory hazards: Exploring lung surfactant inhibition with 20 benchmark chemicals

• Published in: Toxicology (Amsterdam) 2024-05, Vol.504, p.153785-153785, Article 153785
• Main Authors: Liu, James Y., George, Ian C., Hussain, Saber, Sayes, Christie M.
• Format: Article
• Language: English
• Subjects: Animals; Benchmarking; Dose-Response Relationship, Drug; Hazard identification; Hazardous chemicals; High-Throughput Screening Assays - methods; Humans; Lung surfactant; NAM; Pulmonary Surfactants; Respiratory health; Surface tension; Surface Tension - drug effects
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2024.153785

As environmental air quality worsens and respiratory health injuries and diseases increase, it is essential to enhance our ability to develop better methods to identify potential hazards. One promising approach in emerging toxicology involves the utilization of lung surfactant as a model that addresses the limitations of conventional in vitro toxicology methods by incorporating the biophysical aspect of inhalation. This study employed a constrained drop surfactometer to assess 20 chemicals for potential surfactant inhibition. Of these, eight were identified as inhibiting lung surfactant function: 1-aminoethanol, bovine serum albumin, maleic anhydride, propylene glycol, sodium glycocholate, sodium taurocholate, sodium taurodeoxycholate, and Triton X-100. These results are consistent with previously reported chemical-induced acute lung dysfunction in vivo. The study provides information on each chemical's minimum and maximum surface tension conditions and corresponding relative area and contact angle values. Isotherms and box plots are reported for selected chemicals across doses, and vector plots are used to summarize and compare the results concisely. This lung surfactant bioassay is a promising non-animal model for hazard identification, with broader implications for developing predictive modeling and decision-making tools.