Work package 1: Identification of ED targets and relevant EDCs
Identification of ED targets (I. Sylte, K. Kristiansen, L. Evenseth, University of Tromsø)
- Two homology models of ecdysone receptor (EcR) ligand binding domain built
- Molecular docking performed to verify the models and predict potential EcR ligands
- In vitro screening assay established and used to verify the model predictions (In collaboration with T. Iguchi, NIBB)
Computational identification of EDCs (M. Cronin and C. Mellor, Liverpool John Moores Univeristy)
- KNIME workflow developed for identification of possible ecdysone disruptors based on a structural alerts approach using physico-chemical properties of a high number of environmental chemicals.
Cross-species extrapolation (C. LaLone, D. Villeneuve, G. Ankley, USEPA/ University of Minnesota)
- Taxonomic applicability domain beyond cladocerans identified using the Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool
Work package 2: Adverse outcome pathways
Assembly of conceptual AOPs (Y. Song, K.E. Tollefsen, NIVA)
- Conceptual AOPs for EcR agonists assembled based on literature studies
- First invertebrate AOPs for EcR agonists submitted to the AOP-Wiki (OECD)
Roles of ecdysteroids for progression of reproductive cycle in the fresh water crustacean Daphnia magna
(T. Iguchi, NIBB)
- 20-hydroxyecdysone (20E) found to be involved in both molting and reproduction cycle (ovulation) of D. magna
- Ecdysone identified to be synthesized in the gut
- Cyp18a1 gene found to regulate the decline of ecdysteroid titre before molting and ovulation
- Several publications submitted/published on the role of Ecdysone-relevant modulation of molting and reproductive behavior (see publications)
Work package 3: Robustness and applicability
Work package 4: Regulatory contributions
Workshop on “Advancing Adverse Outcome Pathways for Integrated Toxicology and Regulatory Applications” (Garcia-Reyero, N., Becker, R., Barton-Maclaren, T., Carvalho, R., Groh, K., Lettieri, Teresa., Patlewicz, G.Y., Perkins, J.E., Garcia-Reyero, N., Tollefsen, K.E, Villeneuve, D.L.).
A workshop to advance the use of AOPs organized with support from EDRISK funding and personnel. The AOP workshop addressed the following topics:
- Research priorities for development of AOPs.
- Strategic approaches to AOP development.
- Weight of evidence evaluation to define uncertainties associated with predictive relationships represented in an AOP.
- “Acceptance” of AOPs for regulatory applications.
- Applying AOPs to support Informed Approaches to Testing and Assessment.
A number of scientific papers have been submitted for publication in peer-review journals (see publications).