title: Successful validation of in vitro methods in toxicology by ZEBET, the National Centre for Alternatives in Germany at the BfR (Federal Institute for Risk Assessment).
abstract: A short description of the history of the 3Rs concept is given, which was developed as the scientific concept to refine, reduce and replace animal experiments by Russel and Burch more than 40 years ago. In addition, the legal framework in Europe for developing alternatives to animal experiments is given and the current status of in vitro systems in pharmacology and toxicology is described including an update on metabolising systems. The decrease in experimental animal numbers during the past decade in Europe is illustrated by the situation in Germany and the contribution of international harmonisation of test guidelines on reducing animal numbers in regulatory testing is described. A review of the development of the principles of experimental validation is given and the 3T3 NRU in vitro phototoxicity test is used as an example for a successful validation study, which led to the acceptance of the first in vitro toxicity test for regulatory purposes by the OECD. Finally, the currently accepted alternative methods for standardisation and safety testing of drugs, biologicals and medical devices are summarised.
authors.affiliation: ZEBET (National Centre for Documentation and Evaluation of Alternative Methods to Animal Experiments) at the Federal Institute for Risk Assessment (BfR=Bundesinstitut für Risikobewertung), Berlin, Germany. horst.spielmann@bfr.bund.de
authors.forename: Horst
authors.initials: H
authors.lastname: Spielmann
authors.forename: Barbara
authors.initials: B
authors.lastname: Grune
authors.forename: Manfred
authors.initials: M
authors.lastname: Liebsch
authors.forename: Andrea
authors.initials: A
authors.lastname: Seiler
authors.forename: Richard
authors.initials: R
authors.lastname: Vogel
mesh_terms: D000826:Animal Testing Alternatives / Q000331:legislation & jurisprudence*; D000818:Animals; D018929:Cell Culture Techniques; D005062:European Union; D005858:Germany; D017408:Guidelines as Topic; D006801:Humans; D007391:International Cooperation; D018570:Risk Assessment; D018675:Toxicity Tests / Q000379:methods*