Unlocking the future of environmental safety: a framework for integrating new approach methodologies in...

Traditional regulatory frameworks for assessing the environmental safety of chemicals have historically focused on evaluating in vivo data from standard ecologically representative species. This approach relies heavily on apical effect studies performed on whole organisms. However, there is now a strong regulatory and ethical push towards adopting non-animal approaches that incorporate novel methodologies and enhance the mechanistic understanding of toxicological responses across various species. Despite this progress, their implementation in environmental risk assessment remains limited. We propose a conceptual framework for conducting safety assessments that leverages mechanistic data, extending beyond traditional types, to inform environmental safety decisions. This approach aims to support the application of new approach methodologies in environmental risk assessment, without the need for generating additional animal data. We then evaluate the approach with three case studies based on different modes of action, including 17R-Ethinyl Estradiol, Chlorpyrifos, and Tebufenozide. The overall strategy involves the collection and integration of available relevant effect data across human health and the environment to demonstrate the suitability of mechanistic-based information to support and strengthen current practices. The results demonstrate that integrating historical in vivo data, in vitro functional assays, and in silico computational tools enhances confidence in safety decision-making through identification of the most sensitive species where evolutionary conservation of biological targets and toxicological outcomes are in agreement. This approach offers a valuable weight-of-evidence method to understand potential toxicity effects better and points to practical future applications.