Abstract：
For decades, chemical safety assessment has been proposed to shift from animal testing to in vitro testing systems in response to the call for the 3R. In Europe, the answer was to combine various information sources in integrated testing strategies (ITS); In the US, it was in 2007 when the landmark report by the National Research Council put forward a vision of in vitro toxicity testing paradigm. Since then, efforts to develop pathway-based assessment framework have been on the track. In 2010, systems biology brought out a conceptual framework called adverse outcome pathway (AOP), which took one step further from toxicity pathway to regulatory toxicology. Computational modeling, high-throughput screening, high-content omics have all been approached to facilitate this progress. This paper briefly reviewed the achievement of pathway-based chemical assessment since 2007, discussed potential pitfalls and challenges that mechanism-driven chemical assessment may undergo, and presented future perspectives of safety assessment that is to be based on computational system biology.
摘要：
几十年来,为了响应3R的呼吁，已建议化学安全性评估从动物测试转向体外测试系统。在欧洲,答案是在集成测试策略(ITS)中结合各种信息源；在美国，2007年，国家研究委员会的具有里程碑意义的报告提出了体外毒性测试范式的愿景。从那以后,制定基于途径的评估框架的努力已经步入正轨。2010年，系统生物学提出了一个称为不良结果途径(AOP)的概念框架，从毒性途径到调节毒理学更进一步。计算建模,高通量筛选，高含量的组学都被用来促进这一进展。本文简要回顾了自2007年以来基于途径的化学评估的成就，讨论了机制驱动的化学评估可能面临的潜在陷阱和挑战，并提出了基于计算系统生物学的安全评估的未来观点。
