International cooperation: An essential requirement for replacing animal toxicity tests

The Three Rs concept, which was developed by Russell & Burch in 1959, was i mplemented into the legal framework in the European Union (EU) for the prot ection of vertebrate animals used for experimental and other scientific pur poses, when Directive 86/609/EEC was adopted in 1986. One focus of activity under this Directive is the use of animals and alternative methods in regu latory testing. To reduce or replace animal testing for regulatory purposes , non-animal tests must be independently validated to prove that they can p rovide information that is relevant and reliable for hazard prediction in r elation to specific types of toxicity in vivo. At the end of the 1980s, no scientific concept existed for the formal validation of in vitro toxicity t ests, so a small group of European and American scientists met to develop a set of principles for experimental validation, which were first adopted by ECVAM in Europe in 1995, and, after harmonisation with experts from the US A and Japan, accepted internationally by the OECD in 1996. ECVAM has direct ly funded a number of validation studies, and a major breakthrough in the y ear 2000 was the acceptance for regulatory purposes in the EU of scientific ally validated in vitro toxicity tests for phototoxic potential and for ski n corrosivity. These, and other examples which are discussed, confirm that the internationally harmonised ECVAM/ICCVAM/OECD validation concept is a pr actical and effective way of making possible the replacement of regulatory testing in animals.