Abstract:
The Adverse Outcome Pathway (AOP) framework has gained widespread acceptance in toxicological disciplines as a tool for aiding chemical hazard assessment. Despite increased activity in AOP development, progress towards a high volume of fully endorsed AOPs has been slow, partly due to the challenging task of constructing complete AOPs according to the AOP Developer\'s Handbook. To facilitate greater uptake of new knowledge units onto the open-source AOP-wiki platform, a pragmatic approach was recently proposed. This approach involves considering Key Event Relationships (KERs) for individual development through systematic approaches, as they represent essential units of knowledge from which causality can be inferred; from low complexity test data to adverse outcomes in intact organisms. However, more broadly adopted harmonized methodologies for KER development would be desirable. Using the AOP Developer\'s Handbook as a guide, a KER linking \'decreased androgen receptor (AR) activity\' with \'reduced anogenital distance (AGD)\' was developed to demonstrate a methodology applicable for future developments of KERs requiring systematic literature retrieval approaches.
摘要:
不良结果途径(AOP)框架已在毒理学学科中获得广泛接受,作为辅助化学危害评估的工具。尽管AOP开发活动有所增加,在实现大量完全认可的AOPs方面进展缓慢,部分原因是根据AOP开发人员手册构建完整的AOP的挑战性任务。为了促进在开源AOP-wiki平台上更多地吸收新的知识单元,最近提出了一种务实的方法。这种方法涉及通过系统方法考虑个人发展的关键事件关系(KERs),因为它们代表知识的基本单位,可以从完整生物体的低复杂度测试数据中推断出因果关系。然而,更广泛采用的KER发展统一方法将是可取的。使用AOP开发人员手册作为指南,开发了将“雄激素受体(AR)活性降低”与“肛门生殖器距离减少(AGD)”联系起来的KER,以证明适用于需要系统文献检索方法的KER的未来发展的方法。