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Imprint
Database search for the development of a multiorgan chip as an alternative to animal experiments with repeated dose toxicity testing
Project
Project code: BfR-ZEBET-08-1322-599
Contract period: 01.03.2014
- 31.12.2014
Purpose of research: Applied research
Accepted and validated alternative methods are predominately in the area of skin / eye irritation and corrosion. More challenging is, however, the development of non-animal methods for repeated dose toxicity testing. The multiorgan chip technology, where miniaturized organoids are connected on a chip to mimic the conditions in a human body, is a promising approach in this respect. The aim of this project is the optimization of the development of a multiorgan chip by the collection and evaluation of data from toxicological animal experiments. The data should contain information on the study design, the applied chemicals, the dose range, endpoints, and organs. Publicly accessible data bases like the Actor-ToxRefDB of the US EPA contain data, which describe the traits mentioned above. A clustering of organs and endpoints and substances on the basis of the toxicological effect strength should serve the development of a multiorgan chip. In addition commercial databases should be used for elucidating mechanisms of toxicity. Finally the biometric design of substance tests with the multiorgan chip will be carried out.
The aim of this project was to aid the optimization of the development of a multiorgan system by the collection and evaluation of data from toxicological animal experiments. The focus was to obtain information important for the in vitro-detection of neurotoxicity. The extraction of dose effect data for neurotoxic substances by the evaluation of toxicological databases for animal experiments was an important part of the project. The effects of these substances to other organ should be determined this way. The result of the determination should be represented by substance target organ profile. These profiles compiled to matrices were the basis of further analysis. The detection of primary and secondary effect of the substances should be enabled thereby as well as the definition of gold standard for in vitro neurotoxicity. A further objective of the project was the detection of toxicity mechanisms, in order to aid the designs of optimal multiorgan system and to aid the Identification of candidate in vitro biomarker for neurotoxicity. In 2014 the databases necessary for the purpose of the project were identified. A preliminary list of neurotoxic substances yields the base for the definition of gold standard. The evaluation of the data base ToxRef DB has enabled the compilation of dose-target organ -profiles, which indicate possible contributions of organs to neurotoxicity. Further examinations consider in more detail the impact of administration routes on the target organ profiles.
Section overview
Subjects
- Animal health
- Computer science
Framework programme
Funding programme
Excutive institution
BfR - Centre for Documentation and Evaluation of Alternatives to Animal Experiments (BfR - ZEBET)
