Cefic-lri Programme | European Chemical Industry Council

ECO20-UA: Development of an alternative testing strategy for the fish early life-stage test for predicting chronic toxicity

Principal Investigator

Prof. Dr. Dries Knapen
University of Antwerp
Universiteitsplein 1, UC.173
2610 Wilrijk
Belgium
dries.knapen@uantwerpen.be
Tel: +32 3 265 27 24

Collaborators

Prof. Dr. Ronny Blust, University of Antwerp, Belgium, ronny.blust@ua.ac.be
Dr. Hilda Witters, Flemish Institute for Technological Research (VITO), Belgium, hilda.witters@vito.be

Prof. Dr. Gerald Ankley, Environmental Protection Agency (EPA), USA, ankley.gerald@epa.gov

Description

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

Click here to read the project executive summary.

Related Publications

Publications:

A report from the SETAC Global Animal Alternatives Advisory Group: http://globe.setac.org/2014/october/global-animal-alt-ag.html

Direct

An Hagenaars, Evelyn Stinckens, Lucia Vergauwen, Lieven Bervoets, Dries Knapen. PFOS affects posterior swim bladder chamber inflation and swimming performance of zebrafish larvae. Aquat Toxicol. 2014 Dec;157:225-35.

Enise Bagci, Marjolein Heijlen, Lucia Vergauwen, An Hagenaars, Anne M. Houbrechts, Camila V. Esguerra, Ronny Blust, Veerle M. Darras, Dries Knapen. Deiodinase knockdown during early zebrafish development affects growth, development, energy metabolism, motility and phototransduction. PLoS One. 2015 Apr 9;10(4):e0123285.

Lucia Vergauwen, Stine N. Schmidt, Evelyn Stinckens, Walid Maho, Ronny Blust, Philipp Mayer, Adrian Covaci, Dries Knapen. A high throughput passive dosing format for the Fish Embryo Acute Toxicity test. Chemosphere. 2015 Nov;139:9-17.

Dries Knapen, Lucia Vergauwen, Daniel L. Villeneuve, Gerald T. Ankley (2015). The potential of AOP networks for reproductive and developmental toxicity assay development. Reprod Toxicol. 2015 Aug 15;56:52-5.

Krysta R. Nelson, Anthony L. Schroeder, Gerald T. Ankley, Brett R. Blackwell, Chad Blanksma, Sigmund J. Degitz, Kevin M. Flynn, Kathleen M. Jensen, Rodney D. Johnson, Michael D. Kahl, Dries Knapen, Patricia A. Kosian, Rebecca Y. Milsk, Eric C. Randolph, Travis W. Saari, Evelyn Stinckens, Lucia Vergauwen, Daniel L. Villeneuve. Impaired anterior swim bladder inflation following exposure to the thyroid peroxidase inhibitor 2-mercaptobenzothiazole – Part I: fathead minnowAquat Toxicol. 2016 Apr;173:192-203.

Evelyn Stinckens, Lucia Vergauwen, Anthony L. Schroeder, Walid Maho, Brett R. Blackwell, Hilda Witters, Ronny Blust, Gerald T. Ankley, Adrian Covaci, Daniel L. Villeneuve, Dries Knapen. Impaired anterior swim bladder inflation following exposure to the thyroid peroxidase inhibitor 2-mercaptobenzothiazole – Part II: zebrafish. Aquat Toxicol. 2016 Apr;173:204-217.

Indirect

Daniel L. Villeneuve, Doug Crump, Natàlia Garcia-Reyero, Markus Hecker, Thomas H. Hutchinson, Carlie A. LaLone, Brigitte Landesmann, Teresa Lettieri, Sharon Munn, Malgorzata Nepelska, Mary Ann Ottinger, Lucia Vergauwen, Maurice Whelan. Adverse Outcome Pathway (AOP) Development I: Strategies and Principles.  Toxicol Sci. 2014 Dec;142(2):312-20.

Daniel L. Villeneuve, Doug Crump, Natàlia Garcia-Reyero, Markus Hecker, Thomas H. Hutchinson, Carlie A. LaLone, Brigitte Landesmann, Teresa Lettieri, Sharon Munn, Malgorzata Nepelska, Mary Ann Ottinger, Lucia Vergauwen, Maurice Whelan (2014). Adverse Outcome Pathway Development II: Best Practices. Toxicol Sci. 2014 Dec;142(2):321-30.

Edward J. Perkins, Philipp Antczak, Lyle Burgoon, Francesco Falciani, Natàlia Garcia-Reyero, Steve Gutsell, Geoff Hodges, Aude Kienzler, Dries Knapen, Mary McBride, Catherine Willett. Adverse Outcome Pathways for Regulatory Applications: examination of four case studies with different degrees of completeness and scientific confidence. Toxicol Sci. 2015 Nov;148(1):14-25.

Posters :

Lucia Vergauwen, An Hagenaars, Evelyn Stinckens, Lieven Bervoets, Natàlia Garcia-Reyero, Dries Knapen. Mechanism of PFOS effects on posterior swim bladder chamber inflation in zebrafish larvae. SETAC Europe 25th Annual Meeting, May 2015, Barcelona, Spain.

Evelyn Stinckens, Lucia Vergauwen, An Hagenaars, Anthony L. Schroeder, Ronny Blust, Daniel L. Villeneuve, Gerald T. Ankley, Dries Knapen. Effects of disrupting the thyroid hormone (TH) axis on swim bladder inflation in zebrafish . BelTox Annual Meeting, December 2014, Geel, Belgium.

Lucia Vergauwen, Stine N. Schmidt, Walid Maho, Evelyn Stinckens, An Hagenaars, Ronny Blust, Philipp Mayer, Adrian Covaci, Dries Knapen. Passive dosing for the zebrafish embryo test using silicone O-rings. Fish and amphibian embryos as alternative models in toxicology and teratology, December 2014, Aulnay-sous-Bois, France.

Timeline: March 2013 > February 2016

LRI funding: € 499.842

Cefic-Lri Programme Responsible Care

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