International STakeholder NETwork (ISTNET): creating a developmental neurotoxicity (DNT) testing road map for regulatory purposes
International STakeholder NETwork (ISTNET): creating a developmental neurotoxicity (DNT) testing road map for regulatory purposes
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DOI：
10.1007/s00204-015-1464-2
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发表时间：
2015-02-01
影响因子：
6.1
通讯作者：
Fritsche, Ellen
中科院分区：
文献类型：
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作者：
Bal-Price, Anna;Crofton, Kevin M.;Fritsche, Ellen
发育神经毒性（DNT）风险评估的一个主要问题是缺乏大多数化合物的毒理学危害信息。因此，正在考虑新的方法，以提供足够的实验数据，允许监管决策。这一过程一方面需要监管需求与新的测试系统和方法提供的机会相匹配。将学术和工业驱动的检测开发与DNT领域的监管需求相结合是国际权益持有者网络（ISTNET）在DNT检测领域的核心使命。2014年1月23日至24日在苏黎世举行了第一次ISTNET会议，以探讨实际DNT测试的不良结局途径（AOP）概念。AOP被认为是根据监管需求促进测试系统开发的有前途的工具。此外，AOP概念被确定为一个重要的指导原则，组装预测集成测试策略（ITS）的DNT。对基于AOP的DNT测试路线图的建议被认为是一种逐步的方法，最初使用不完整的AOP进行化合物分组，并专注于神经发育的关键事件。在后续活动中要考虑的下一步是使用案例研究，以进一步将AOP概念应用于监管DNT测试，利用AOP交叉点（常见关键事件）进行筛选测定的经济发展，并解决从定性描述到定量网络建模的过渡。
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.