Reynolds Jacob I, Choi Judy, Johnson Brian P
Department of Biomedical Engineering, Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI 48824, USA.
Department of Pesticides Safety, Unit Toxicology of Active Substances and their Metabolites, German Federal Institute for Risk Assessment, 10589 Berlin, Germany.
Curr Res Toxicol. 2024 Aug 8;7:100191. doi: 10.1016/j.crtox.2024.100191. eCollection 2024.
Chemical risk assessment still primarily relies on extrapolation of data from high-confidence studies. Emerging 21st Century Toxicology tools and approaches have potential to figure more prominently in chemical risk assessment, but many challenges in translating this research into assessments remain. One of these tools, the Adverse Outcome Pathway (AOP) Wiki provides a framework to map and evaluate adverse chemical dynamics, that is the biochemical and physiological effects that occur after chemical exposure. The AOP-guided targeted review of relevant literature, described here, shares similarities with a doctoral thesis or literature review but forces critical evaluation of each step in a pathway including those of central dogma. Additionally, it provides valuable translational regulatory relevance. Data gaps identified through this process can be targeted areas of study in the thesis itself to increase translational relevance. One of the challenges with this tool is that many AOPs are under- or undeveloped. To help fill this need, a concerted effort by subject matter experts to speed the development of AOPs supported under the Organization for Economic Cooperation and Development (OECD) framework would benefit this translational problem. As a case study, we present our experience developing AOP 460: Antagonism of Smoothened receptor leading to orofacial clefting (OECD AOP workplan project 1.101) as part of a graduate literature review. AOP development offers clear benefits to the regulatory and academic communities and increased dissemination of AOPs replete with the most current state of scientific knowledge will promote research translation and increased risk assessment capabilities.
化学风险评估仍然主要依赖于从高可信度研究中推断数据。21世纪新兴的毒理学工具和方法有可能在化学风险评估中发挥更突出的作用，但将这项研究转化为评估仍面临许多挑战。其中一种工具，即不良结局途径（AOP）维基，提供了一个框架来绘制和评估不良化学动力学，也就是化学物质暴露后发生的生化和生理效应。本文所述的基于AOP的相关文献定向综述，与博士论文或文献综述有相似之处，但它促使对一条途径中的每一步进行批判性评估，包括那些中心法则的步骤。此外，它还具有宝贵的与监管相关的转化意义。通过这一过程确定的数据空白可以成为论文本身的目标研究领域，以提高转化相关性。该工具面临的挑战之一是许多AOP尚未充分开发或尚未开发。为满足这一需求，主题专家齐心协力加快在经济合作与发展组织（OECD）框架下支持的AOP的开发，将有助于解决这一转化问题。作为一个案例研究，我们介绍了作为研究生文献综述的一部分，开发AOP 460：平滑受体拮抗导致口面部裂隙（OECD AOP工作计划项目1.101）的经验。AOP的开发对监管和学术界都有明显益处，更广泛地传播包含最新科学知识状态的AOP将促进研究转化并提高风险评估能力。
