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

University of Antwerp
Universiteitsplein 1, UC
2610 Wilrijk
Belgium
Prof. Dr. Dries Knapen
Tel: +32 3 265 33 49
Fax: +32 3 265 34 97

Collaborators

Prof. Dr. Ronny Blust, University of Antwerp, BE
Dr. Hilda Witters, Flemish Institute for Technological Research (VITO), BE
Prof. Dr. Gerald Ankley, Environmental Protection Agency (EPA), USA

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

Related Publications

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).

Posters :

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).

More publications:

Direct

Hagenaars A., Stinckens E., Vergauwen L., Bervoets L., Knapen D. (2014). PFOS affects posterior swim bladder chamber inflation and swimming performance of zebrafish larvae. Aquatic Toxicology. 157, 225-235.

Link: https://www.sciencedirect.com/science/article/pii/S0166445X14003208

Bagci E., Heijlen M., Vergauwen L., Hagenaars A., Houbrechts A.M., Esguerra C.V., Blust R., Darras V.M., Knapen D. (2015). Deiodinase knockdown during early zebrafish development affects growth, development, energy metabolism, motility and phototransduction. PLoS One. 10, e0123285.

Link: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0123285

Vergauwen L., Schmidt S.N., Stinckens E., Maho W., Blust R., Mayer P., Covaci A., Knapen D. (2015) A high throughput passive dosing format for the Fish Embryo Acute Toxicity test. Chemosphere 139, 9-17.

Link: https://www.sciencedirect.com/science/article/pii/S0045653515005044?via%3Dihub

Knapen D., Vergauwen L., Villeneuve D.L., Ankley G.T. (2015). The potential of AOP networks for reproductive and developmental toxicity assay development. Reproductive Toxicology 56, 52-55.

Link: https://www.sciencedirect.com/science/article/pii/S0890623815000581?via%3Dihub

Nelson KR, Schroeder AL, Ankley GT, Blackwell BR, Blanksma C, Degitz SJ, Flynn KM, Jensen KM, Johnson RD, Kahl MD, Knapen D, Kosian PA, Milsk RY, Randolph EC, Saari T, Stinckens E, Vergauwen L, Villeneuve DL. 2016. Impaired anterior swim bladder inflation following exposure to the thyroid peroxidase inhibitor 2-mercaptobenzothiazole – Part I: fathead minnow. Aquatic Toxicology 173:192-203

Link: https://www.sciencedirect.com/science/article/pii/S0166445X15301399?via%3Dihub

Stinckens E, Vergauwen L, Schroeder AL, Maho W, Blackwell BR, Witters H, Blust R, Ankley GT, Covaci A, Villeneuve DL, Knapen D. 2016. Impaired anterior swim bladder inflation following exposure to the thyroid peroxidase inhibitor 2-mercaptobenzothiazole – Part II: zebrafish. Aquatic Toxicology 173:204-217

Link: https://www.sciencedirect.com/science/article/pii/S0166445X15301387

Indirect

Villeneuve D.L., Crump D., Garcia-Reyero N., Hecker M., Hutchinson T.H., LaLone C.A., Landesmann B., Lettieri T., Munn S., Nepelska M., Ottinger M.A., Vergauwen L., Whelan M. 2014. Adverse Outcome Pathway (AOP) Development I: Strategies and Principles. Toxicological Sciences 142, 312-320.

Link: https://academic.oup.com/toxsci/article/142/2/312/1621273

Villeneuve D.L., Crump D., Garcia-Reyero N., Hecker M., Hutchinson T.H., LaLone C.A., Landesmann B., Lettieri T., Munn S., Nepelska M., Ottinger M.A., Vergauwen L., Whelan M. 2014. Adverse Outcome Pathway Development II: Best Practices. Toxicological Sciences 142, 321-330.

Link: https://academic.oup.com/toxsci/article/142/2/321/1621315

Perkins E, Antczak P, Burgoon L, Falciani F, Garcia-Reyero N, Gutsell S, Hodges G, Kienzler A, Knapen D, McBride M, Willett C. 2015. Adverse Outcome Pathways for Regulatory Applications: examination of four case studies with different degrees of completeness and scientific confidence. Toxicological Sciences 148(1):14-25.

Link: https://academic.oup.com/toxsci/article/148/1/14/1661066

Timeline: March 2013 > February 2016

LRI funding: € 499.842

Cefic-Lri Programme Responsible Care

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