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

Not initiated.

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).

Sist oppdatert 09.02.2015