-New TF- Read-across/QSAR/MoA (environment)

Background

It is widely accepted that pharmaceuticals differ from common chemicals in that they act through specific, receptor-mediated biological mechanisms. While this ‘biological activity' is often held up as a cause for heightened environmental concern it can, if properly understood, serve to target ecotoxicological testing and prioritisation strategies. The specificity of pharmaceutical mechanisms implies that biologic activity should be limited to species possessing like receptors. The extensive pharmacodynamic / toxicodynamic information available for pharmaceuticals coupled with an improved understanding of phylogenetic differentiation of environmental species will support the application of Intelligent Testing Strategies to environmental risk assessment of pharmaceuticals.

Similarly, the ‘specificity' of pharmaceuticals renders most quantitative structure-activity relationship (QSAR) models developed for common chemicals ineffective for pharmaceuticals. Given the broad knowledge-base compiled during research and development, QSARs can be better ‘trained' to predict environmental outcomes for pharmaceutical. The development of pharmaceutical-specific QSARs with high levels of concordance will serve to eliminate the need for some testing and aid in the identification of pivotal / priority tests.

Terms of Reference

• Organise the collation of published literature describing/cataloguing ‘receptor conservation' in environmental species: This is expected to help identify likely susceptible species.
  
• Organise the compilation of pharmaceutical-specific environmental data (published and proprietary) with the aim to develop a robust training set for QSAR development. Priority should be given to seeking data relating to the susceptibilities identified from ToR 1.
  
• Assess whether the outcomes of ToR 1 & 2 are sufficiently robust to develop reliable ‘quantitative' estimates or if only ‘qualitative' susceptibility predictions is a more realistic goal.
  
• If the outcome of ToR 3 is the qualitative prediction route, recommend a scheme of approaches for application of the predictions in combination with ECETOC TR No. 102 (Intelligent Testing Strategies in Ecotoxicology: Mode of Action Approach for Specifically Acting Chemicals) and learnings from the US EPA TOXCAST programme to prioritise pharmaceuticals for further research.
  
• The results of the task force activities should be reported in form of a peer- reviewed paper in a high impact journal in order to reach a wider audience.