School of Pharmacy and Biomolecular Sciences, 4589Liverpool John Moores University, Liverpool, UK.
99013European Commission, Joint Research Centre (JRC), Ispra, Italy.
Altern Lab Anim. 2020 Jul;48(4):146-172. doi: 10.1177/0261192920965977. Epub 2020 Oct 29.
Across the spectrum of industrial sectors, including pharmaceuticals, chemicals, personal care products, food additives and their associated regulatory agencies, there is a need to develop robust and reliable methods to reduce or replace animal testing. It is generally recognised that no single alternative method will be able to provide a one-to-one replacement for assays based on more complex toxicological endpoints. Hence, information from a combination of techniques is required. A greater understanding of the time and concentration-dependent mechanisms, underlying the interactions between chemicals and biological systems, and the sequence of events that can lead to apical effects, will help to move forward the science of reducing and replacing animal experiments. modelling, assays, high-throughput screening, organ-on-a-chip technology, omics and mathematical biology, can provide complementary information to develop a complete picture of the potential response of an organism to a chemical stressor. Adverse outcome pathways (AOPs) and systems biology frameworks enable relevant information from diverse sources to be logically integrated. While individual researchers do not need to be experts across all disciplines, it is useful to have a fundamental understanding of what other areas of science have to offer, and how knowledge can be integrated with other disciplines. The purpose of this review is to provide those who are unfamiliar with predictive tools, with a fundamental understanding of the underlying theory. Current applications, software, barriers to acceptance, new developments and the use of integrated approaches are all discussed, with additional resources being signposted for each of the topics.
在包括制药、化工、个人护理产品、食品添加剂及其相关监管机构在内的各个工业领域，都需要开发强大而可靠的方法来减少或替代动物测试。人们普遍认识到，没有一种单一的替代方法能够完全替代基于更复杂毒理学终点的测定。因此，需要结合多种技术的信息。更深入地了解化学物质与生物系统相互作用的时间和浓度依赖性机制，以及导致顶端效应的事件序列，将有助于推动减少和替代动物实验的科学发展。建模、测定、高通量筛选、器官芯片技术、组学和数学生物学，可以提供互补信息，以全面了解生物体对化学应激原的潜在反应。不良结局途径（AOP）和系统生物学框架使来自不同来源的相关信息能够进行逻辑整合。虽然单个研究人员不需要成为所有学科的专家，但了解其他科学领域提供的内容以及如何将知识与其他学科整合是很有用的。本文的目的是为那些不熟悉预测工具的人提供对基础理论的基本理解。当前的应用、软件、接受障碍、新的发展以及综合方法的使用都进行了讨论，并为每个主题都提供了额外的资源。
