Predicting Respiratory Toxicity Using a Human 3D Airway (EpiAirway™) Model Combined with Multiple Parametric Analysis

Abstract

Abstract There is a growing need to develop, validate, and utilize new in vitro alternatives to animal toxicity testing in both chemical and personal care industries. In the past, analysis of respiratory toxicity was performed using animal models; however, these studies are costly and time-consuming. An in vitro human tissue model combined with multiple endpoint analysis could provide a robust model for evaluating many types of respiratory toxicity. The objective of this study was to assess the potential for an in vitro three-dimensional human airway model (EpiAirway™) to accurately predict respiratory toxicity in humans. This was done by exposing EpiAirway tissues to known respiratory toxicants and assessing tissue viability (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide [MTT] assay and histology), oxidative stress of the tissues (cellular glutathione [GSH] levels), and gene expression of classical markers for inflammation, metabolic activity, and apoptosis by quantitative real-time revers...