The Adverse Outcome Pathways (AOPs) framework is pivotal in toxicology, but the, terminology describing Key Event Relationships (KERs) varies within AOP guidelines.This study examined the usage of causal, observational and predictive terms in AOP, documentation and their adaptation in AOP development. A literature search and text, analysis of key AOP guidance documents revealed nuanced usage of these terms, with KERs often described as both causal and predictive. The adaptation of, terminology varies across AOP development stages. Evaluation of KER causality often, relies targeted blocking experiments and weight-of-evidence assessments in the, putative and qualitative stages. Our findings highlight a potential mismatch between,terminology in guidelines and methodologies in practice, particularly in inferring,causality from predictive models. We argue for careful consideration of terms like, causal and essential to facilitate interdisciplinary communication. Furthermore, integrating known causality into quantitative AOP models remains a challenge.

中文翻译：

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因果关系、预测性还是观察性？对不良结局途径的关键事件关系及其对实践的影响的不同理解


不良结果途径 （AOP） 框架在毒理学中至关重要，但描述关键事件关系 （KER） 的术语在 AOP 指南中有所不同。本研究检查了 AOP、文档及其在 AOP 开发中因果、观察和预测术语的使用及其改编。文献检索和文本分析揭示了这些术语的细微用法，其中 KER 通常被描述为因果关系和预测性。术语的适应因 AOP 开发阶段而异。KER 因果关系的评估通常依赖于推定和定性阶段的靶向阻断实验和证据权重评估。我们的研究结果强调了指南中的术语与实践中的方法之间的潜在不匹配，特别是在推断中，预测模型的因果关系。我们主张仔细考虑诸如 causal 和 essential 之类的术语，以促进跨学科交流。此外，将已知的因果关系整合到定量 AOP 模型中仍然是一个挑战。