The main objective of this project is to use a mechanistic framework to develop and propose a high-throughput tiered-testing strategy for screening and prioritizing chemicals for FELS testing (OECD 210). The main objective can be divided into four parts:
1) Establish a database of toxicologically relevant FELS-specific AOPs, identify molecular initiating events and subsequent intermediate responses resulting into the apical outcome of interest
2) Propose Tier 1 in vitro screening toolbox to test for AOP-specific events and responses predictive for FELS chronic toxicity.
3) Propose Tier 2 whole-organism ZFET assays to test for AOP-specific events and responses predictive for FELS chronic toxicity and assess the potential of a ZFET molecular screening tool to predict cellular, organ and/or organism responses giving rise to FELS chronic toxicity.
4) Offering a proposal for implementation of a tiered-testing strategy in EU regulation. Assessment of usefulness and applicability of tiered testing strategy for global scientific and regulatory community
A report from the SETAC Global Animal Alternatives Advisory Group: http://globe.setac.org/2014/october/global-animal-alt-ag.html
Executive summary :
Development of an alternative testing strategy for the fish early life-stage test for predicting chronic toxicity by Vergauwen L., Stinckens E., Michiels E.D.G., Hagenaars A., Bagci E., Claes L., Hollanders K., Jacobs A., Berckmans P., Verstraelen S., Schroeder A. L., Blackwell B. R., Xavallin J. E., Nelson K. R., Dardenne F., Blust R., Villeneuve D. L., Ankley G. T., Witters H., Knapen D. (March 2016).
Mechanism of PFOS effects on posterior swim bladder chamber inflation in zebrafish larvae by Vergauwen L., Hagenaars A., Stinckens E., Bervoets L., Garcia-Reyero N. and Knapen D. (May 2015).
Effects of disrupting the thyroid hormone (TH) axis on swim bladder inflation in zebrafish by Stinckens E., Vergauwen L., Hagenaars A., Schroeder A.L., Blust R., Villeneuve D.L., Ankley G.T. and Knapen D. (December 2014).
Passive dosing for the zebrafish embryo test using silicone O-rings by Vergauwen L., Schmidt S., Maho W., Stinckens E., Hagenaars A., Blust R., Mayer P., Covaci A. and Knapen D. (December 2014).