Validation of the Rat Limb Bud Micromass Test in the International ECVAM Validation Study on Three In Vitro Embryotoxicity Tests

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.

[1]  Aldert H Piersma,et al.  Validation of the Postimplantation Rat Whole-embryo Culture Test in the International ECVAM Validation Study on Three In Vitro Embryotoxicity Tests , 2004, Alternatives to laboratory animals : ATLA.

[2]  Susanne Bremer,et al.  Validation of the Embryonic Stem Cell Test in the International ECVAM Validation Study on Three In Vitro Embryotoxicity Tests , 2004, Alternatives to laboratory animals : ATLA.

[3]  T. Tsuchiya,et al.  Teratogenicity of arotinoids (retinoids) in vivo and in vitro , 2005, Archives of Toxicology.

[4]  Horst Spielmann,et al.  Screening Chemicals for Reproductive Toxicity: The Current Alternatives , 1995 .

[5]  Michael Balls,et al.  The Role of Prevalidation in the Development, Validation and Acceptance of Alternative Methods , 1995 .

[6]  Aldert Piersma,et al.  The ECVAM International Validation Study on In Vitro Embryotoxicity Tests: Results of the Definitive Phase and Evaluation of Prediction Models , 2002, Alternatives to laboratory animals : ATLA.

[7]  A. Kistler Limb bud cell cultures for estimating the teratogenic potential of compounds , 1987, Archives of Toxicology.

[8]  N. Brown Selection of Test Chemicals for the ECVAM International Validation Study on In Vitro Embryotoxicity Tests , 2002, Alternatives to laboratory animals : ATLA.

[9]  O. Flint,et al.  Structure-Teratogenicity Relationships Among Antifungal Triazoles , 1990 .

[10]  H. Spielmann,et al.  Reproduction and development. , 1998, Environmental health perspectives.

[11]  Spielmann Horst,et al.  Practical Aspects of the Validation of Toxicity Test Procedures , 1995 .

[12]  H. Spielmann,et al.  The embryonic stem cell test (EST), an in vitro embryotoxicity test using two permanent mouse cell lines : 3T3 fibroblasts and embryonic stem cells , 1997 .

[13]  J. Stadler,et al.  The Comparative Testing of Eight Coded Chemicals in the Rat Limb Bud Micromass and Rat Embryo Culture Systems , 1996 .

[14]  M. J. Norušis,et al.  SPSS professional statistics 6.1 , 1994 .

[15]  O. Flint,et al.  An in vitro assay for teratogens with cultures of rat embryo midbrain and limb bud cells. , 1984, Toxicology and applied pharmacology.

[16]  A. Piersma,et al.  Development of prediction models for three in vitro embryotoxicity tests in an ECVAM validation study. , 2000, In vitro & molecular toxicology.

[17]  Michael Sjöström,et al.  Recommendations for the Application of Biostatistical Methods during the Development and Validation of Alternative Toxicological Methods , 1996 .