Bruner L H, Carr G J, Chamberlain M, Curren R D
The Procter and Gamble Company, Health and Beauty Care Europe, Egham, Surrey TW20 9NW, UK; The Procter and Gamble Company, Miami Valley Laboratories, Cincinnati, OH 45253-8707, USA.
Toxicol In Vitro. 1996 Aug;10(4):479-501. doi: 10.1016/0887-2333(96)00028-8.
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.
为了评估替代方法作为体内毒性试验替代方法的有效性，已经开展了许多研究。本综述的目的是在这项工作过程中所学到的知识基础上，提出一个可用于开展未来验证计划的实用流程。已经介绍了一个明确表述的预测模型的重要作用，该模型定义了如何使用替代方法的结果来预测体内毒性终点。计算机模拟已被用于证明可以开发基于数据的指南，以协助判断在验证研究中评估的替代方法的性能。此外，还使用了统计程序，以便为选择验证研究中合适的参考测试物质数量和参与实验室数量提供指导。眼刺激试验替代方法的验证被用作一个具体例子来说明重要概念。虽然讨论的重点是旨在取代当前体内试验的替代方法的验证，但这些程序可用于评估用于其他用途的替代方法的性能。本综述对于那些需要进行验证研究实用指南的人以及那些必须评估此类计划结果的人将特别有用。
