Alternatives to animal testing – CEllSens

Predicting toxicity of chemicals to fish using fish cell lines and fish embryos

Fish are the most frequently used vertebrates in regulatory ecotoxicology. Numerous OECD guidelines depend on the use of fish, including OECD 203 (acute fish test), OECD 210 (early life stage toxicity test) and OECD 305 (bioconcentration test). As vertebrates, fish are legally protected animals. Therefore, alternatives to reduce or replace fish tests for risk assessment of chemicals and industrial effluents are of high societal importance. In addition to being more ethical and economical, alternative approaches may also offer better insights into the modes of action underlying the toxicity of chemicals to fish.

We therefore aim to provide the scientific background that helps improve fish embryo and fish cell line assays to achieve international acceptance as alternatives to the acute fish toxicity test for the risk assessment of chemicals. In a transatlantic endeavor, the CEFIC-LRI/UK DEFRA funded CEllSens-Eco8 project, we currently follow the hypothesis that alternative approaches need to take bioavailability and internal concentrations into account, need to reflect different chemical target sites and respond to chemicals with different modes of action [1,2]. Research is guided by models that are based on structure-activity correlations (QSAR models).

Within a new EU Marie Curie Training Site on Mechanistic Effect Models for Ecological Risk Assessment of Chemicals (CREAM, [3]) we will follow the hypothesis that the information obtained in cell cultures and fish can be brought together in a two-step model (considering the toxicokinetics and toxicodynamics of the chemicals) to be able to predict responses of fish based on cells.

[1] Schirmer, K., Tanneberger, K., Kramer, N.I., Völker, D., Scholz, S., Hafner, C., Lee, L.E.J., Bols, N.C., Hermens, J.L.M. (2008). Developing a list of reference chemicals for testing alternatives to whole fish toxicity tests. Aquatic Toxicology 90, 128-137.

[2] Schirmer, K. (2006). Proposal to improve vertebrate cell cultures to establish them as substitutes for the regulatory testing of chemicals and effluents using fish. Toxicology 224, 163-183.

[3] Grimm, V., Ashauer R., Forbes, V., Hommen, U., Preuss, T.G., Schmidt, A., van den Brink, P.J., Wogram, J., Thorbek, P. (2009). CREAM: A European Project on Mechanistic Effect Models for Ecoloigcal Risk Assessment of Chemicals. ESPR, in press.