Bearth Angela, Kopainsky Birgit, Jones Lowenna B, Vist Gunn E, Husøy Trine, Svendsen Camilla, Whaley Paul, Hoffmann Sebastian, Ames Heather M, Solstad Gisle, Bloch Denise, Čavoški Aleksandra, Chiu Weihsueh A, Davenport Miles, Davies Holly G, Giusti Arianna, Hartung Thomas, Kwon Seok, Osborne Olivia J, Rooney Andrew A, Rousselle Christophe, Sass Jennifer B, Wright Fred A, Mathisen Gro H
Norwegian Scientific Committee for Food and Environment, Norwegian Institute of Public Health, Oslo, Norway.
HF Partners, Tièchestrasse 63, 8037, Zurich, Switzerland.
Arch Toxicol. 2025 Sep 9. doi: 10.1007/s00204-025-04168-z.
The transition from traditional animal-based approaches and assessments to New Approach Methodologies (NAMs) marks a scientific revolution in regulatory toxicology, with the potential of enhancing human and environmental protection. However, implementing the effective use of NAMs in regulatory toxicology has proven to be challenging, and so far, efforts to facilitate this change frequently focus on singular technical, psychological or economic inhibitors. This article takes a system-thinking approach to these challenges, a holistic framework for describing interactive relationships between the components of a system of interest. In this case, the regulatory toxicology system. We do so by analysing and interpreting a very large qualitative data set of experts' observations, collected in a 3-day interactive workshop and three follow-up online workshops with a heterogeneous sample of experts representing major actors from the global regulatory toxicology system. We identified leverage points (where a small change within a system can have a disproportionately large effect) in the six core aspects-infrastructure, processes, culture, technology, goals, and actors-in the regulatory toxicology system to facilitate the effective use of NAMs. Identified systematic leverage points include the need for a functioning incentive structure for effectively discovering, developing, validating and using NAMs within academia, regulation, and industry; and measures that prevent or mitigate unwanted effects of using NAMs that acknowledge clashes between scientific, regulatory, political and social processes. The results serve as a basis for follow-up activities that reflect on the actual effectiveness of these levers and that develop measures for the regulatory toxicology system.
从传统的基于动物的方法和评估向新方法学（NAMs）的转变标志着监管毒理学领域的一场科学革命，具有加强人类和环境保护的潜力。然而，事实证明，在监管毒理学中有效使用新方法学具有挑战性，到目前为止，促进这一转变的努力往往集中在单一的技术、心理或经济障碍上。本文采用系统思维方法来应对这些挑战，系统思维是一种用于描述感兴趣系统各组成部分之间相互作用关系的整体框架。在这种情况下，即监管毒理学系统。我们通过分析和解读一个非常庞大的定性数据集来做到这一点，该数据集来自在一个为期3天的互动研讨会以及随后的三个在线研讨会上收集的专家观察结果，参与这些研讨会的专家样本具有多样性，代表了全球监管毒理学系统中的主要参与者。我们在监管毒理学系统的六个核心方面——基础设施、流程、文化、技术、目标和参与者——中确定了杠杆点（系统内的一个小变化可能会产生不成比例的重大影响之处），以促进新方法学的有效使用。确定的系统性杠杆点包括需要建立一个有效的激励结构，以便在学术界、监管机构和行业内有效地发现、开发、验证和使用新方法学；以及采取措施预防或减轻使用新方法学带来的不良影响，这些措施要考虑到科学、监管、政治和社会进程之间的冲突。这些结果为后续活动提供了基础，这些活动将反思这些杠杆的实际有效性，并为监管毒理学系统制定措施。
