Exploring experiences of the regulatory toxicology system : system-level promoters and inhibitors of new approach methodologies

Bearth, Angela and Kopainsky, Birgit and Jones, Lowenna B and Vist, Gunn E and Husøy, Trine and Svendsen, Camilla and Whaley, Paul and Hoffmann, Sebastian and Ames, Heather M and Solstad, Gisle and Bloch, Denise and Čavoški, Aleksandra and Chiu, Weihsueh A and Davenport, Miles and Davies, Holly G and Giusti, Arianna and Hartung, Thomas and Kwon, Seok and Osborne, Olivia J and Rooney, Andrew A and Rousselle, Christophe and Sass, Jennifer B and Wright, Fred A and Mathisen, Gro H (2025) Exploring experiences of the regulatory toxicology system : system-level promoters and inhibitors of new approach methodologies. Archives of Toxicology. ISSN 0340-5761

Abstract

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.