ATLA::Alternatives to Laboratory Animals

Volume 32, Number 3

Validation of the rat limb bud micromass test in the international ECVAM validation study on three in vitro embryotoxicity tests

H. Spielmann1, E. Genschow2, N.A. Brown3, A.H. Piersma4, A. Verhoef4, M.Q.I. Spanjersberg4, H. Huuskonen5, F. Paillard6 & A. Seiler1

1Centre for Documentation and Evaluation of Alternative Methods to Animal Experiments (ZEBET) at the BfR, Berlin, Germany; 2Federal Institute for Risk Assessment (BfR), Berlin, Germany; 3St George's Hospital Medical School, University of London, UK; 4National Iinstitute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands; 5National Public Health Institute (KTL Finland), Kuopio, Finland; 6Sanofi-Synthelabo Recherche, Porcheville, France

SUMMARY

A detailed report is presented on the performance of the rat limb bud micromass (MM) test in a European Centre for the Evaluation of Alternative Methods (ECVAM)-sponsored formal validation study on three in vitro tests for embryotoxicity. Twenty coded test chemicals, classified as non-embryotoxic, weakly embryotoxic or strongly embryotoxic on the basis of their in vivo effects on animals and/or humans, were tested in four laboratories. The outcome showed that the MM test is an experimentally validated test, which holds promise for use for identifying strongly embryotoxic chemicals, but which needs to be improved before it can be recommended for use for regulatory purposes.

Keywords: ECVAM, in vitro embryotoxicity test, in vitro toxicology, micromass, prediction model, prevalidation, rat embryo limb buds, validation