formance of new tests. The important point for this report is that validation is now seen as a formal, although flexible, process that new tests must satisfy to be accepted by regulators. The details of validation exercises may vary as one shifts from in vitro and in vivo tests to -omics and computational toxicology techniques.


One of the tensions in designing new chemical-testing strategies is between reducing animal use and suffering and regulatory needs for more information on a wider array of chemicals or more detailed information on a smaller group of chemicals. Russell and Burch (1992) provided a framework for addressing that tension. They proposed that scientists pursue techniques and approaches that follow the Three Rs, namely, methods that can replace or reduce animal use in specific procedures or refine animal use to eliminate or decrease animal suffering. Replacement, reduction, and refinement have also come to be known as alternative methods.

First proposed in 1959, the Three Rs approach (3Rs) advanced in the 1980s when cosmetics and consumer-product companies began to invest millions of dollars in alternative methods in response to consumer pressure (Stephens et al. 2001). During that same decade, national governments incorporated the Three Rs approach into their animal-protection legislation and in some cases began to fund research on and development of alternatives, academic centers devoted to the alternatives began to be established, the field of in vitro toxicology blossomed, and companies began to market alternative test kits. In the 1990s, government centers devoted to the validation and regulatory acceptance of alternative methods were established in Europe and the United States, alternative tests began to be formally approved and accepted by regulatory agencies, and the triennial World Congresses on Alternatives were inaugurated. There is evidence that, owing in part to the implementation of Three Rs approaches, use of laboratory animals in research and testing in the United States decreased by about 30%1 in the decade after the estab


Estimate based on comparison of average number of Animal Welfare Act (AWA)-covered animals used per year in 1994-2003 and average number of AWA-covered animals used per year in 1984-1993. Source: Animal Welfare Reports, USDA/APHIS.

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