WORKSHOP OVERVIEW - SCIENTIFIC AND REGULATORY CHALLENGES FOR THE REDUCTION, REFINEMENT, AND REPLACEMENT OF ANIMALS IN TOXICITY TESTING

Public concern for animal welfare has been expressed through legislati ve control of animal use for experimental purposes since the first leg islation was introduced in 1876 in the United Kingdom. Legislative con trol of animal use has been introduced in virtually every developed co untry, with major initiatives in Europe (1986) and the United States ( 1966 and 1985). Advances in scientific thinking resulted in the develo pment of the concept of the three Rs-refinement, reduction, and replac ement-by Russell and Burch in 1959, The field has expanded substantial ly since, with specialist scientific journals dedicated to alternative s, World Congresses organized to discuss the scientific and philosophi cal issues, and European and U.S. validation organizations being launc hed. Current scientific attention is focused on validation of alternat ive methods. The underlying scientific principles of chemical toxicity are complicated and insufficiently understood for alternative methods for all toxicity endpoints of importance in protecting human health t o be available. Important lessons have been learned about how to valid ate methods, including the need to have prediction models available be fore the validation is undertaken, the need to understand the variabil ity of the animal-based data which is to be used as the validation sta ndard, and the need to have well-managed validation programs. Future p rogress will depend on the development of novel methods, which can now be validated through international collaborative efforts. (C) 1998 So ciety of Toxicology.