Extrapolation of In Vitro Acrolein Dose-Response Derived in Air-Liquid-Interface Airway Epithelial Models to In Vivo Lung Toxicity
Extrapolation of In Vitro Acrolein Dose-Response Derived in Air-Liquid-Interface Airway Epithelial Models to In Vivo Lung Toxicity
Principal Investigator: Xuefei Cao and Sheila Healy
Funding Mechanism: Internal FDA
ID number: E07603.01
Award Date: 10/22/2015
Institution: National Center for Toxicological Research (NCTR)
New methods for conducting risk assessments that could reduce or replace animal testing would be valuable for assessing the human health effects of tobacco product use. Advancements in in vitro tissue models and physiologically-based computational modeling provide a potential means for better using in vitro mammalian cell assays to make quantitative assessments of human risk. This study will combine an in vitro human testing model with a chemical-specific strategy to use in vitro results to predict human responses. In this study, researchers will evaluate acrolein toxicity in human lung cell culture and air-liquid-interface (ALI) airway tissue models derived from both rat and human bronchial epithelial cells using toxicity endpoints relevant to human respiratory disease. Dose-response relationships derived from in vitro rat ALI toxicity data will then be compared with corresponding in vivo rat dose-response relationships to derive an in vitro-to-in vivo extrapolation factor for each toxicity endpoint. This extrapolation factor, along with human in vitro toxicity data, will then be input into mathematical models to predict in vivo human responses. The methodology developed in this study may allow scientists to evaluate claims of equivalent or modified health risks of tobacco products without animal testing.