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Imprint
Joint Project: Development of an in vitro embryo toxicity tests with mouse embryonic stem cells: Subproject 1 - Analysis of embryotoxic effects in the light of new endpoints and metabolism using an expanded selection of materials
Project
Project code: BfR-ZEBET-08-1334-168
Contract period: 01.04.2004
- 31.12.2007
Purpose of research: Applied research
Improving a murine embryonic stem cell-based in vitro embryotoxicity test (phase II): Incorporation of cellular metabolism, establishment of new developmental endpoints and extension to new substance classes Assessing toxicity of chemicals for development and the reproductive cycle requires extensive screening and multi-generation studies. For chemicals used as drugs, segment studies have to be conducted covering preconceptional exposure as well as preand postnatal development including the lactation period (guidelines of the InternationalConference on Harmonization, ICH, 1993). These in vivo test methods are time-consuming, expensive and have to be carried out on high numbers of laboratory animals. Therefore, new predictive screens for risk assessment with respect to developmental toxicity need to be developed with the ultimate goal of reducing animal use and testing more chemicals than can be accommodated by conventional whole-animal testing. In vitro alternatives such as whole embryo cultures and cellular models using primary cultures and permanent cell lines have been developed. In the most recently developed test, the embryonic stem cell test (EST), blastocystderivedpluripotent embryonic stem (ES) cells of the mouse are used to assess the embryotoxic potential of test chemicals. In an international ECVAM validation study the EST has been demonstrated to bea reliable nonanimal test system for embryotoxicity using a set of 20 reference compounds characterized by high quality in vivo embryotoxicity data assessed in laboratory animals andhumans. In a joint research project funded by the BMBF the EST protocol has been successfully improved by establishing molecular endpoints of differentiation in cultured ES cells. In this novelapproach the expression level of tissuespecific marker proteins under influence of the test chemical are quantified by intracellular flow cytometry and Real-Time TaqMan-PCR.
Section overview
Subjects
- Special animal species
- Biotechnology
Framework programme
Funding programme
Excutive institution
BfR - Centre for Documentation and Evaluation of Alternatives to Animal Experiments (BfR - ZEBET)
