Establishment of normal human neural progenitor cells as an in vitro screening model for the evaluation of the neurotoxic potential of chemicals
Description:
The new EU Regulation on dealing with registration, evaluation, authorisation and restriction of chemical substances (REACH) entered into force of 1 June 2007. REACH demands the evaluation of the neurotoxic potential of chemicals which are produced with a volume > 1t. This includes new as well as existing chemicals. Currently, neurotoxicity testing is based on OECD guidelines and demands in vivo experiments. These consume high numbers of animals (approx, 350/chemical) and take up to 1 year. With regard to the 30,000 chemicals which are supposed to fulfill REACH criteria within the next 5 years, in vivo testing is ethically questionable and economically on the verge of impossibility.The development of a standardized, predictive cell culture based (in vitro) screening model for evaluating neurotoxic potentials of chemicals will reduce the number of animals and shorten the testing time. Additionally an in vitro test system provides better control of the experimental environment (e.g. local chemical concentration) as well as better observation and intervention possibilities on a cellular level (e.g. microscopy, micromanipulation) than animal experiments. This enables the observation of toxic effects and the investigation of the underlying mechanisms on a cellular level. Therefore, our goal is mechanism-based hazard assessment of chemicals for the human nervous system in an in vitro system.Normal neural human progenitor cells are an established cell culture model for investigating developmental neurotoxicity in our lab. The goal of this project is to evaluate if these cells are suited for the detection of neurotoxic threats to the adult nervous system.Therefore, neurospheres will be cultured for an extended time period (1-4 weeks). In these ?aging? cultures, we will (i) investigate if cells mature, (ii) establish endpoints which predict neurotoxicity and (iii) check for reliability of these endpoints by using selected and well know neurotoxins.
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. 2007 - 31. 07. 2010
Participating Institutions:
- Leibniz Research Institute for Environmental Medicine (IUF) Details of IUF
Funding Programme:
- BfR Funding Details of BfR Funding
Subject:
- Biotechnology
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