Fernando Ruani N, Chaudhari Umesh, Escher Sylvia E, Hengstler Jan G, Hescheler Jürgen, Jennings Paul, Keun Hector C, Kleinjans Jos C S, Kolde Raivo, Kollipara Laxmikanth, Kopp-Schneider Annette, Limonciel Alice, Nemade Harshal, Nguemo Filomain, Peterson Hedi, Prieto Pilar, Rodrigues Robim M, Sachinidis Agapios, Schäfer Christoph, Sickmann Albert, Spitkovsky Dimitry, Stöber Regina, van Breda Simone G J, van de Water Bob, Vivier Manon, Zahedi René P, Vinken Mathieu, Rogiers Vera
Department of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
Centre of Physiology and Pathophysiology, Institute of Neurophysiology and Centre for Molecular Medicine Cologne (CMMC), 50931 Cologne, Germany.
Arch Toxicol. 2016 Jun;90(6):1529-1539. doi: 10.1007/s00204-016-1719-6. Epub 2016 Apr 29.
SEURAT-1 is a joint research initiative between the European Commission and Cosmetics Europe aiming to develop in vitro- and in silico-based methods to replace the in vivo repeated dose systemic toxicity test used for the assessment of human safety. As one of the building blocks of SEURAT-1, the DETECTIVE project focused on a key element on which in vitro toxicity testing relies: the development of robust and reliable, sensitive and specific in vitro biomarkers and surrogate endpoints that can be used for safety assessments of chronically acting toxicants, relevant for humans. The work conducted by the DETECTIVE consortium partners has established a screening pipeline of functional and "-omics" technologies, including high-content and high-throughput screening platforms, to develop and investigate human biomarkers for repeated dose toxicity in cellular in vitro models. Identification and statistical selection of highly predictive biomarkers in a pathway- and evidence-based approach constitute a major step in an integrated approach towards the replacement of animal testing in human safety assessment. To discuss the final outcomes and achievements of the consortium, a meeting was organized in Brussels. This meeting brought together data-producing and supporting consortium partners. The presentations focused on the current state of ongoing and concluding projects and the strategies employed to identify new relevant biomarkers of toxicity. The outcomes and deliverables, including the dissemination of results in data-rich "-omics" databases, were discussed as were the future perspectives of the work completed under the DETECTIVE project. Although some projects were still in progress and required continued data analysis, this report summarizes the presentations, discussions and the outcomes of the project.
SEURAT-1是欧盟委员会与欧洲化妆品协会之间的一项联合研究计划,旨在开发基于体外和计算机模拟的方法,以取代用于评估人类安全性的体内重复剂量全身毒性试验。作为SEURAT-1的组成部分之一,DETECTIVE项目聚焦于体外毒性测试所依赖的一个关键要素:开发强大、可靠、灵敏且特异的体外生物标志物和替代终点,用于对人类具有相关性的慢性作用毒物的安全性评估。DETECTIVE联盟合作伙伴开展的工作建立了一个功能和“组学”技术的筛选流程,包括高内涵和高通量筛选平台,以在细胞体外模型中开发和研究用于重复剂量毒性的人类生物标志物。以基于途径和证据的方法识别和统计选择高度预测性的生物标志物,是朝着在人类安全性评估中替代动物试验的综合方法迈出的重要一步。为了讨论该联盟的最终成果和成就,在布鲁塞尔组织了一次会议。此次会议汇聚了数据生成和支持联盟合作伙伴。报告聚焦于正在进行和即将结束的项目的当前状态,以及用于识别新的相关毒性生物标志物所采用的策略。会议讨论了成果和可交付成果,包括在富含数据的“组学”数据库中传播结果,以及DETECTIVE项目下已完成工作的未来展望。尽管一些项目仍在进行中,需要持续进行数据分析,但本报告总结了报告内容、讨论情况和该项目成果。