ExITox – Explain Inhalation Toxicity

Development of an integrated testing strategy for the prediction of toxicity after repeated-dose inhalation exposure: a proof of concept.

A collaborative project funded by the German Federal Ministry of Education and Research (BMBF) in the funding program "e:ToP –  Innovative Toxicology for the Reduction of Animal Experimentation"

Coordinator: The project is being coordinated by Dr. Sylvia Escher, Fraunhofer Institute for Toxicology and Experimental Medicine ITEM. The six participants of the consortium are from Hannover, Freiburg, Göttingen, and Wolfenbüttel.

Contract period: January 1, 2017 – March 31, 2020

Grant no.: 031 L0120A

Summary: This project is aimed at developing an integrated testing strategy (ITS) for human health risk assessment of repeated-dose toxicity after inhalation exposure so as to replace de-novo animal testing. Five groups of compounds with shared toxicological effects were selected and tested with human precision-cut lung slices (PCLS) and human pulmonary cell cultures in order to identify group-specific biomarkers that indicate a shared mode of action. PCLS and cell cultures were exposed to airborne substances via air-liquid technology using the Fraunhofer ExpoCube®. Genome-wide transcriptome analyses using the TempoSeq technology were performed in these models and the data were evaluated using bioinformatics methods.

Beside hazard characterization in vitro, EXITOX-II also aims to better predict the bioavailability of airborne compounds. To achieve this goal, the scientists are developing a physiologically based pharmacokinetic (PBPK) model that defines three compartments to model the respiratory tract in humans. Currently, in-vitro parameters such as apparent permeability coefficients are applied to parameterize this model.

The outcome of this project will be a proposal for an integrated testing strategy for respiratory toxicity. 

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