FRAME Annual Lecture. International co-operation: an essential requirement for replacing animal toxicity tests.
The Three Rs concept, which was developed by Russell and Burch in 1959, was implemented into the legal framework in the European Union (EU) for the protection of vertebrate animals used for experimental and other scientific purposes, 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 regulatory testing. To reduce or replace animal testing for regulatory purposes, non-animal tests must be independently validated to prove that they can provide information that is relevant and reliable for hazard prediction in relation 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 tests, 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 USA and Japan, accepted internationally by the OECD in 1996. ECVAM has directly funded a number of validation studies, and a major breakthrough in the year 2000 was the acceptance for regulatory purposes in the EU of scientifically validated in vitro toxicity tests for phototoxic potential and for skin corrosivity. These, and other examples which are discussed, confirm that the internationally harmonised ECVAM/ICCVAM/OECD validation concept is a practical and effective way of making possible the replacement of regulatory testing in animals.