Introduction The goals of the regulatory toxicology of chemicals are to ensure the occupational safety of workers dur- ing the production of chemicals, to ensure the safety of food and beverages, to protect patients against possible hazards represented by drugs and medical devices, and to protect humans and the environment against possible hazards posed by residues of chem- icals such as pesticides. The standard approach in regulatory toxicology to assess the toxicity of chem- icals is the determination of toxic properties in stan- dardised animal tests, as described in the OECD Guidelines for the Testing of Chemicals (1) or in the European Union (EU) official test methods for chemicals, published in Annex V to Directive 67/548/EEC (2) on the classification, packaging and labelling of dangerous substances. This information is used by European regulators, in the first step of the current risk-assessment procedure, to classify each chemical according to internationally har- monised guidelines (for example, as harmful, toxic or irritant), and to label them in the second step, according to EU risk (R) phrases (for example, R- 41: risk of serious damage to the eye). The conse- quences of classification and labelling are the restricted use of the tested chemical in finished products (depending on exposure), and safety and labelling recommendations. The international harmonisation of toxicity tests by the OECD in 1982 was the first and, so far, the most effective, step in reducing duplication of test- ing in animals for regulatory purposes, since a toxi- city test conducted according to an OECD guideline will be accepted by regulatory agencies in all OECD Member Countries. These Member Countries are the worlds major industrial nations. Since 1990, a similar approach has been used for the safety and efficacy testing of drugs, as a result of the International Conference on Harmonisation (ICH), which represents the three major economic regions, Europe, Japan and the USA (3). Further reductions in regulatory toxicity testing in animals can only be achieved if animal tests are replaced by non-animal or alternative toxicity tests. However, regulators will only accept alterna- tives to animal tests in toxicology, if the new tests will allow them to classify and label chemicals in the same way as the results of the current animal tests permit. The OECD has therefore decided that in vitro toxicity tests can only be accepted for regu- latory purposes after a successful validation, in order to scientifically prove that the new in vitro toxicity test will provide the same level of protec- tion for humans and the environment as is provided by the currently applied animal tests. To approach this problem scientifically, Euro- pean and American scientists interested in the val- Validation Successes: Chemicals Horst Spielmann and Manfred Liebsch National Centre for Documentation and Evaluation of Alternative Methods to Animal Experiments (ZEBET), Federal Institute for Health Protection of Consumers and Veterinary Medicine (BgVV), Diedersdorfer Weg 1, 12277 Berlin, Germany Summary  The ECVAM validation concept, which was defined at two validation workshops held in Amden (Switzerland) in 1990 and 1994, and which takes into account the essential elements of prevalida- tion and biostatistically defined prediction models, has been officially accepted by European Union (EU) Member States, by the Federal regulatory agencies of the USA, and by the OECD. The ECVAM validation concept was introduced into the ongoing ECVAM/COLIPA validation study of in vitro phototoxicity tests, which ended successfully in 1998. The 3T3 neutral red uptake in vitro phototoxicity test was the first exper- imentally validated in vitro toxicity test recommended for regulatory purposes by the ECVAM Scientific Advisory Committee (ESAC). It was accepted by the EU into the legislation for chemicals in the year 2000. From 1996 to 1998, two in vitro skin corrosivity tests were successfully validated by ECVAM, and they were also officially accepted into the EU regulations for chemicals in the year 2000. Meanwhile, in 2002, the OECD Test Guidelines Programme is considering the worldwide acceptance of the validated in vitro photo- toxicity and corrosivity tests. Finally, from 1997 to 2000, an ECVAM validation study on three in vitro embryotoxicity tests was successfully completed. Therefore, the three in vitro embryotoxicity tests, the whole embryo culture (WEC) test on rat embryos, the micromass (MM) test on limb bud cells of mouse embryos, and the embryonic stem cell test (EST) including a permanent embryonic mouse stem cell line, are considered to be scientifically valid and appropriate for routine use in laboratories of the European pharmaceutical and chemicals industries. Key words: chemicals, corrosivitiy, ECVAM, embryotoxicity, European Commission, in vitro toxicity, photo- toxicity, regulatory toxicology, skin irritation, validation. ATLA 30, Supplement 2, 3340, 2002 33