Electronic Signatures (ESigns) as a Mechanistic Integration Layer for NAM-Based Regulatory Safety Assessment

This project aims to develop and validate Electronic Signatures (ESigns) as a mechanistic, physics-based descriptor framework to support next-generation safety assessment in regulatory and industry contexts. ESigns encode molecular properties derived from first-principles electronic structure calculations and provide a reproducible, explainable representation of chemical reactivity, interaction potential, and biological perturbation capacity.

The project will integrate ESigns with established New Approach Methodologies (NAMs), including in vitro assays, organoid systems, and other non-animal platforms, by providing mechanistic context for observed biological responses. ESigns will be mapped to Molecular Initiating Events (MIEs) and Adverse Outcome Pathways (AOPs), enabling consistent interpretation across experimental systems and supporting weight-of-evidence decision making.

A central objective is to assess the role of ESigns in regulatory hazard identification and risk prioritisation, including their use as a mechanistic alternative or complement to analogue-based read-across. By grounding similarity and grouping in electronic and mechanistic equivalence rather than purely structural analogy, the approach aims to improve transparency, applicability to novel chemical space, and scientific justification within OECD-aligned NAM frameworks.

The outcome will be a scalable, auditable, and future-proof methodology that enhances regulatory confidence in NAM-based safety assessment while reducing reliance on animal testing and historical datasets alone.