Comments on the scientific validation and regulatory acceptance of in vitro toxicity tests.

The 1980s saw widespread acceptance of the Three Rs (reduction, refinement, replacement) concept of alternatives, and a great deal of effort was put into the development of non-animal toxicity tests. Yet, although new methods are gaining acceptance as pre-screens and as adjunct methods, there is little sign that any of them will be accepted as genuine replacements for current animal test procedures. This is partly because, until recently, the question of scientific validation for relevance, reproducibility and transferability had not been properly addressed, and partly because, despite national and international laws that require that replacement alternatives be used wherever possible, little attention had been paid to promotion of their formal acceptance into regulatory toxicology. Reference is made to the recommendations of two workshops organized by members of ERGATT (European Research Group for Alternatives in Toxicity Testing) early in 1990-on validation (with the Johns Hopkins Center for Alternatives to Animal Testing) and on regulatory acceptance (with the support of the Commission of the European Communities)-which could provide a basis for meeting this challenge in the 1990s. It is argued, however, that primary responsibility for the effective and orderly development, validation, independent assessment and regulatory acceptance of non-animal toxicity tests should rest with in vitro toxicologists themselves.