Improvement of the embryonic stem cell test (EST) using neural marker genes for testing the developmental neurotoxicity in vitro
Description:
Given the significant potential of chemicals and drugs to interfere with development of the nervous system, regulatory test guidelines have been adopted for the prediction and as-sessment of developmental neurotoxicity (U.S.EPA OPPTS 870.6300 and OECD TG 426). However, current in vivo test methods are laborious, costly and necessitate the use of high numbers of laboratory animals. Around 1000 pups have to be handled in an in vivo DNT study and at least 140-mated dams are used to produce enough pups from different litters available to the tests. Moreover, the study design is complex and clear and straight-forward recommendations for optimal methodological approaches in DNT studies are not available to date. In addition, under the REACH program of the European Commission it is planned to evaluate approximately 30,000 existing chemicals for their toxicological properties. Predic-tion of developmental neurotoxic effects is a key feature in the toxicological profile of a com-pound and triggered DNT studies are recommended under REACH (ECHA, May, 2008). This situation certainly will dramatically increase the number of laboratory animals used for toxicity testing. Conversely, validated alternative methods for developmental neurotoxicity testing are still not available to date. Thus, standardized, predictive screens for the evalua-tion of developmental neurotoxicity soon need to be made available with the ultimate goal of increased efficiency in terms of reduced animal use and higher throughput compared to whole-animal testing using existing guidelines.
Executive Institute:
BfR - Centre for Documentation and Evaluation of Alternatives to Animal Experiments (BfR - ZEBET) Details of BfR - Centre for Documentation and Evaluation of Alternatives to Animal Experiments
Parent institution:
Federal Institute for Risk Assessment (BfR) Details of (BfR) (Berlin)
Contract period:
01. 08. 2004 - 31. 12. 2010
Participating Institutions:
- University of Veterinary Medicine Hannover (TiHo) Details of TiHo
- University of Rostock Details of University of Rostock
- BASF SE Details of BASF SE
- Institute for Health and Consumer Protection (JRC IHCP) Details of JRC IHCP
- Leibniz Research Institute for Environmental Medicine (IUF) Details of IUF
- Proteosys - Innovation in Proteomics and Systems Biology Details of Proteosys - Innovation in Proteomics and Systems Biology
Funding Programme:
- BfR Funding Details of BfR Funding
Subject:
- Animal health
Purpose of research:
Applied research
Funding Institutions:
- Federal Institute for Risk Assessment (BfR) Details of (BfR)
Project Management Agency:
- Federal Institute for Risk Assessment (BfR) Details of BfR