Common Liquid Application Dosing Conditions Alter Toxicity Testing Endpoints in Air-Liquid Interface Primary Human Bronchial Epithelial Cultures
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SOT 2024 Abstract
Background and Purpose: The use of in vitro systems to model the effects of inhalation exposures has focused on using differentiated primary human bronchial epithelial cell (dpHBEC) cultures as they recapitulate key features of the airway epithelium in vivo. Achieving physiological relevance with these models require cultures to be maintained under air-liquid interface (ALI) conditions. Conducting in vitro exposures while maintaining ALI conditions is technically challenging and requires specialized equipment. Thus, validating potential adverse effects typically involves applying an aqueous solution containing the test substance to the surface of ALI cultures. While practical, liquid application abolishes the ALI conditions that are a critical aspect of the dpHBEC system. Despite being commonly used, the impact of liquid application on ALI culture phenotype and response to experimental exposures is poorly understood. The resulting lack of context in which to interpret data from these studies limits their integration into decision making. To address this knowledge gap and advance understanding of how to use these systems in inhaled chemical testing, we sought to characterize the effects of commonly used liquid application dosing conditions on in vivo physiologically-relevant endpoints in dpHBEC cultures.