Validation of alternative methods for toxicity testing.

Many studies have been conducted in order to assess the validity of alternative methods as replacements forin vivo toxicity tests. The purpose of this review is to build on what has been learned in the course of this work by presenting a practical process that can be used to conduct future validation programmes. The important role of a clearly stated prediction model, which defines how to use the results from an alternative method to predict anin vivo toxicity endpoint, has been introduced. Computer simulations have been used to demonstrate that data-based guidance can be developed to assist in judging the performance of alternative methods assessed in a validation study. Additionally, statistical procedures have been used in order to provide guidance on choosing the appropriate number of reference test substances and number of participating laboratories to include in a validation study. The validation of alternative methods for eye irritation testing is used as a specific example to illustrate important concepts. Although the focus of the discussion is on the validation of alternative methods intended to replace currentin vivo tests, the procedures can be used to assess the performance of alternative methods intended for other uses. This review will be particularly useful to those who require a practical guide for conducting a validation study and to those who must assess the results of such programmes.