The term “New Approach Methodologies” (NAMs) comprises a plethora of approaches with the potential for testing the safety, efficacy, and biological effects of chemicals, pharmaceuticals, and other substances without relying exclusively on traditional animal testing methodologies. While it is debateable whether “new” is the appropriate terminology – some NAMs have been around for several decades, while others have been developed recently – many scholars have observed that the effective uptake of NAMs in regulatory toxicology remains a challenge. The interdisciplinary CHANGE project applies a systems thinking approach to this challenge by modelling the behaviour of the regulatory toxicology system shaped by system-level factors and their interconnections. This article reports findings from two three-day workshops held in Oslo in summer 2024 (Workshop 1 “Explore”) and 2025 (Workshop 2 “Reflect”) with experienced practitioners from regulatory agencies, industry, civil society organisations and academia. Through structured collaborative activities, including small- and large-group discussions, modelling exercises and reflection activities, considerable qualitative data was gathered. Most sessions were recorded, transcribed, and analysed using a multi-step thematic analysis explicitly guided by systems thinking principles, enabling the identification of systemic structures and feedback mechanisms and their visualization in the form of a systems model. Insights from Workshop 1 “Explore” were revisited and stress-tested in Workshop 2 “Reflect”, deepening the robustness of the resulting systems model. This systems model shows structural, economic, social, cultural and technical factors that are interlinked through reinforcing and balancing feedback loops that promote or inhibit the effective use of NAMs. The systems model shows potential leverage points for system change, for instance enhancing the stability and reliability of the supply chain or ensuring that actors in the regulatory toxicology system have both educational and institutional support to effectively change established practices.