Prevalidation of the <i>ex vivo</i> model precision cut lung slices (PCLS) for predicting respiratory toxicology
This third-party funded project is conducted in the framework of the BfR research program for alternatives to animal experiments.
Support code of the Federal Ministry of Education and Research: FKZ 0315720A
The aim of the PCLS method is the reduction of the number of animals used in inhalation toxicity tests. In the framework of the project the method was prevalidated using 20 substance tests and five endpoints.
Part of the BfR
The task of the BfR in the framework of the contract was biometric consulting. This comprised the introduction of standardized data storage, curve fitting dose-response relationships, the evaluation of the reproducibility of the method and the development a prediction model.
More than 900 dose-response relationships have been analyzed for the 20 substances. The results show a good reproducibility within each laboratory for two endpoints: mitochondrial activity (WST-1 assay) and protein content (BCA assay). A high consistency between the laboratories was observed for these endpoints too. The application of the latter for a prediction model yielded an acceptable sensitivity of the method.