Bal-Price Anna, Crofton Kevin M, Leist Marcel, Allen Sandra, Arand Michael, Buetler Timo, Delrue Nathalie, FitzGerald Rex E, Hartung Thomas, Heinonen Tuula, Hogberg Helena, Bennekou Susanne Hougaard, Lichtensteiger Walter, Oggier Daniela, Paparella Martin, Axelstad Marta, Piersma Aldert, Rached Eva, Schilter Benoît, Schmuck Gabriele, Stoppini Luc, Tongiorgi Enrico, Tiramani Manuela, Monnet-Tschudi Florianne, Wilks Martin F, Ylikomi Timo, Fritsche Ellen
Systems Toxicology Unit, EURL-ECVAM, Institute for Health and Consumer Protection, European Commission, Joint Research Centre, TP 580, Via Fermi 1, 21026, Ispra, VA, Italy,
Arch Toxicol. 2015 Feb;89(2):269-87. doi: 10.1007/s00204-015-1464-2. Epub 2015 Jan 25.
A major problem in developmental neurotoxicity (DNT) risk assessment is the lack of toxicological hazard information for most compounds. Therefore, new approaches are being considered to provide adequate experimental data that allow regulatory decisions. This process requires a matching of regulatory needs on the one hand and the opportunities provided by new test systems and methods on the other hand. Alignment of academically and industrially driven assay development with regulatory needs in the field of DNT is a core mission of the International STakeholder NETwork (ISTNET) in DNT testing. The first meeting of ISTNET was held in Zurich on 23-24 January 2014 in order to explore the concept of adverse outcome pathway (AOP) to practical DNT testing. AOPs were considered promising tools to promote test systems development according to regulatory needs. Moreover, the AOP concept was identified as an important guiding principle to assemble predictive integrated testing strategies (ITSs) for DNT. The recommendations on a road map towards AOP-based DNT testing is considered a stepwise approach, operating initially with incomplete AOPs for compound grouping, and focussing on key events of neurodevelopment. Next steps to be considered in follow-up activities are the use of case studies to further apply the AOP concept in regulatory DNT testing, making use of AOP intersections (common key events) for economic development of screening assays, and addressing the transition from qualitative descriptions to quantitative network modelling.
发育神经毒性（DNT）风险评估中的一个主要问题是大多数化合物缺乏毒理学危害信息。因此，人们正在考虑采用新方法来提供足够的实验数据，以支持监管决策。这一过程一方面需要匹配监管需求，另一方面需要新测试系统和方法所提供的机会。使学术和工业驱动的检测方法开发与DNT领域的监管需求保持一致，是国际利益相关者网络（ISTNET）在DNT测试方面的核心使命。ISTNET的第一次会议于2014年1月23日至24日在苏黎世举行，旨在探讨不良结局途径（AOP）概念在实际DNT测试中的应用。AOP被认为是根据监管需求促进测试系统开发的有前景的工具。此外，AOP概念被确定为组装DNT预测性综合测试策略（ITS）的重要指导原则。关于基于AOP的DNT测试路线图的建议被认为是一种逐步推进的方法，最初使用不完整的AOP对化合物进行分组，并关注神经发育的关键事件。后续活动中需要考虑的下一步是利用案例研究在监管DNT测试中进一步应用AOP概念，利用AOP交叉点（共同关键事件）促进筛选检测方法的经济开发，以及解决从定性描述到定量网络建模的过渡问题。
