Development of Predictive In Vitro Test for Developmental Neurotoxicity testing

Project

Food and consumer protection

This project contributes to the research aim 'Food and consumer protection'. Which funding institutions are active for this aim? What are the sub-aims? Take a look:
Food and consumer protection

Project code: BfR-ZEBET-08-1334-176
Contract period: 01.05.2007 - 31.08.2011
Purpose of research: Applied research

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 assessment of developmental neurotoxicity (U.S.EPA OPPTS 870.6300 and OECD TG 426). However, current in vivo test methods are laborious, costly and necessitate use of high numbers of laboratory animals. Around 1000 pups have to be handled in an in vivo DNT study and at lest 140-mated dams are used to produce enough pups from different litters available to the tests. Moreover, the study design is complex and clear recommendations for optimal methodological approaches in DNT studies are lacking. In addition, under the REACH program of the European Commission it is planned to evaluate approximately 30,000 existing chemicals for their toxicological properties. Prediction of developmental neurotoxic effects is a key feature in the toxicological profile of a compound. This situation will considerably increase the number of laboratory animals. Validated alternative methods for developmental neurotoxicity testing are not available. Thus, standardized, predictive screens for the evaluation of developmental neurotoxicity need to be available with the ultimate goal of increased efficiency in terms of reduced animal use and higher throughput compared to whole-animal testing using the existing guidelines. The final goal of this research proposal is to develop standardized predictive cell-based in vitro assays for developmental neurotoxicity testing. Different complementary cell models which represent selected developmental stages of the developing brain in vivo will be investigated to predict developmental neurotoxicity in vivo from in vitro data. These cell models are: (1) embryonic stem cells, (Dr. A. Seiler, Dr. K. Hayess; BfR, Berlin und Prof. Dr. A. Schrattenholz, Dr. M. Klemm; ProteoSys AG, Mainz),(2) human neural progenitor cells (Dr. E. Fritsche, Dr. T. Rockel;)

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