ExITox – Explain Inhalation Toxicity
A collaborative project funded by the German Federal Ministry of Education and Research (BMBF) in the funding program “e:ToP – Innovative Toxikologie zur Reduzierung von Tierversuchen”Coordinator:
The project was coordinated by Dr. Sylvia Escher, Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM) in Hannover, Germany. The 6 participants of the consortium are from Hannover, Freiburg, Göttingen, and Wolfenbüttel.

Contract period: November 1st, 2013 – October 31st, 2015, extended until January 31st, 2016
Grant no.: 031 A269 D

This project aims at developing an integrated testing strategy (ITS) for the human health risk assessment of repeated dose toxicity after inhalation exposure for the replacement of de novo animal testing. In the pilot phase chemicals with different mode of action will be selected and tested with human precision cut lung slices (PCLS) and human pulmonary cell cultures in order to identify route specific biomarkers. Genome wide transcriptome analyses will be conducted in these models and evaluated using bioinformatics methods. These results will be complemented with data mining results and QSAR predictions. Further, structurally related chemicals will be tested in addition to investigate the possibility of the test system to support read across. The outcome of this pilot project will be a proposal for an integrated testing strategy for respiratory toxicity. Further validation e.g. testing of a broader spectrum of chemicals is foreseen in a follow up project. The proposed ITS, the developed methodologies on data sharing and data integration are not limited to the evaluation of transcriptome data but allow to integrate proteome and metabolome data in a follow up project.
It is geneXplain’s task to analyze transcriptome data of the partners and contribute to the specification of new biomarkers.

Further information:
Homepage of the project at Fraunhofer ITEM
Fraunhofer-Datenbank RepDose
Research Database at Albert Ludwigs University Freiburg (in German)

Koschmann, J., Bhar, A., Stegmaier,P., Kel, A. E. and Wingender, E. (2015) “Upstream Analysis”: An integrated promoter-pathway analysis approach to causal interpretation of microarray data. Microarrays 4, 270-286. doi:10.3390/microarrays4020270. Link

Niehof, M., Hildebrandt, T., Danov, O., Arndt, K., Koschmann, J., Dahlmann, F., Hansen, T. and Sewald, K. (2017) RNA isolation from precision-cut lung slices (PCLS) from different species. BMC Res. Notes 10, 121. doi: 10.1186/s13104-017-2447-6. Link

The project continues with ExITox-II.