Liverpool John Moores University and FRAME recently conducted a research project 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 the REACH system. This paper focuses on the prospects for using alternative methods (both in vitro and in silico) for mutagenicity (genotoxicity) and carcinogenicity testing--two toxicity endpoints, which, together with reproductive toxicity, are of pivotal importance for the REACH system. The manuscript critically discusses well-established testing approaches, and in particular, the requirement for short-term in vivo tests for confirming positive mutagenicity, and the need for the rodent bioassay for detecting non-genotoxic carcinogens. Recently-proposed testing strategies focusing on non-animal approaches are also considered, and our own testing scheme is presented and supported with background information. This scheme makes maximum use of pre-existing data, computer (in silico) and in vitro methods, with weight-of-evidence assessments at each major stage. The need for the improvement of in vitro methods, to reduce the generation of false-positive results, is also discussed. Lastly, ways in which reduction and refinement measures can be used are also considered, and some recommendations are made for future research to facilitate the implementation of the proposed testing scheme.

译文

:利物浦约翰摩尔大学和FRAME最近进行了由Defra赞助的研究项目,该研究项目涉及欧盟REACH(化学品注册,评估和授权)系统中动物测试替代品的现状,以进行化学品安全性测试和风险评估。该项目涵盖了与REACH系统相关的所有主要毒性终点。本文重点介绍了使用替代方法(体外和计算机模拟)进行致突变性(遗传毒性)和致癌性测试的前景-两个毒性终点以及生殖毒性对于REACH系统至关重要。该手稿严格地讨论了已建立的测试方法,尤其是对短期的体内测试以确认阳性诱变性的要求,以及对啮齿动物生物测定法以检测非遗传毒性致癌物的需求。还考虑了最近提出的针对非动物方法的测试策略,并提出了我们自己的测试方案并提供了背景信息的支持。该方案最大程度地利用了现有数据,计算机(计算机模拟)和体外方法,并在每个主要阶段进行了证据权重评估。还讨论了改进体外方法以减少假阳性结果的产生的需求。最后,还考虑了减少和改进措施的使用方法,并为将来的研究提出了一些建议,以促进拟议的测试方案的实施。

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