Grindon Christina, Combes Robert, Cronin Mark T D, Roberts David W, Garrod John F
FRAME, Nottingham, UK.
Altern Lab Anim. 2008 Oct;36 Suppl 1:139-47. doi: 10.1177/026119290803601s11.
This paper presents some results of a joint research project conducted by FRAME and Liverpool John Moores University, and sponsored by Defra, on the status of alternatives to animal testing with regard to the European Union REACH (Registration, Evaluation and Authorisation of Chemicals) system for the safety testing and risk assessment of chemicals. The project covered all the main toxicity endpoints associated with REACH. This paper focuses on the use of alternative (non-animal) methods (both in vitro and in silico) for repeat dose (sub-acute, sub-chronic and chronic) toxicity testing. It reviews the limited number of in silico and in vitro tests available for this endpoint, and outlines new technologies which could be used in the future, e.g. the use of biomarkers and the 'omics' technologies. An integrated testing strategy is proposed, which makes use of as much non-animal data as possible, before any essential in vivo studies are performed. Although none of the non-animal tests are currently undergoing validation, their results could help to reduce the number of animals required for testing for repeat dose toxicity.
本文介绍了由FRAME和利物浦约翰摩尔斯大学联合开展、由英国环境、食品和农村事务部资助的一个研究项目的一些成果，该项目针对欧盟关于化学品安全测试和风险评估的化学品注册、评估、授权和限制（REACH）体系，研究动物试验替代方法的现状。该项目涵盖了与REACH相关的所有主要毒性终点。本文重点关注用于重复剂量（亚急性、亚慢性和慢性）毒性测试的替代（非动物）方法（包括体外和计算机模拟方法）。文中回顾了可用于该终点的有限数量的计算机模拟和体外测试，并概述了未来可能会使用的新技术，例如生物标志物的使用和“组学”技术。本文提出了一种综合测试策略，即在进行任何必要的体内研究之前，尽可能多地利用非动物数据。尽管目前没有任何非动物测试正在进行验证，但它们的结果有助于减少重复剂量毒性测试所需的动物数量。
