Deliverable 1. Roadmaps to assess the environmental effects of pharmaceuticals and their degradation products/metabolites. (M44)

WG4 serves as the main reference Working Group for integrating environmental considerations throughout the drug discovery and development process within COST Action CA21111 OneHealthdrugs. Its role is to connect compound design and early computational prediction with experimental environmental fate assessment, ecotoxicology, identification and characterisation of metabolites and degradation products, mechanistic studies, and integrated environmental risk assessment.

The WG4 reference framework is based on a proactive, tiered and integrated approach, moving environmental assessment from a late-stage regulatory activity towards an integral component of drug discovery. Environmental properties are progressively considered from early compound design and lead selection through candidate development, environmental exposure, transformation and risk characterisation.

Core areas of reference

• Early environmental assessment and prediction – integration of physicochemical properties, degradability, persistence, bioaccumulation and predicted ecotoxicity into early compound profiling.
• Environmental fate and exposure – assessment of degradation, transformation, persistence, mobility, environmental compartments and exposure scenarios.
• Ecotoxicology – evaluation of effects on non-target organisms using organism-level, cellular, behavioural, developmental, reproductive, physiological and receptor-based endpoints.
• Metabolites and degradation products – identification, structural characterisation, prioritisation and comparative assessment of environmentally relevant transformation products.
• Mechanistic ecotoxicology – application of biomarkers, receptor-based assays, transcriptomics, proteomics, metabolomics and other omics approaches.
• Adverse Outcome Pathways (AOPs) – mechanistic interpretation linking molecular initiating events and biological responses to adverse outcomes.
• Integrated environmental risk assessment – integration of hazard, exposure, environmental fate, biological effects and uncertainty.
• Sustainable-by-design – translation of environmental findings into medicinal chemistry, candidate prioritisation, structural redesign, mitigation and alternative-candidate selection.