It is the goal of this research project to investigate if in vitro approaches based on fish cell lines and/or fish embryos can be improved to be widely accepted as an alternative to the acute fish test. With regard to the cell lines, four issues will be addressed in an attempt to overcome the seemingly lower absolute sensitivity. Firstly, several fish cell lines possessing origin-specific differentiated functions will be employed. Secondly, the cell culture environment during toxicity testing will be altered to increase the sensitivity of cells. Thirdly, a variety of endpoints will be used in order to better reflect different modes of toxic action. Finally, the truly bio-available fraction of each chemical, rather than the nominally added concentration, will be taken into account for concentration-response analysis. This latter issue will also be addressed for the same set of chemicals in the DarT. Thus, we set out to systematically explore the capabilities and limitations of each of the in vitro systems compared to the currently accepted in vivo approach.
Kramer et al. Quantifying Processes Determining the Free Concentration of Phenathrene in Basal Cytotoxicity Assays. Chemical Research in Toxicology, 2012, 25, 436-445.
Kramer et al. Development of a Partition-Controlled Dosing System for Cell Assays. Chemical Research in Toxicology, 2010, 23, 1806-1814.
Tannenberger et al. Effects of Solvents and Dosing Procedure on Chemical Toxicity in Cell-Based in Vitro Assays. Environmental Science Technology, 2010, 44, 4775-4781.
Kramer et al. The influence of modes of action and physicochemical properties of chemicals on the correlation between in vitro and acute fish toxicity data. Toxicology In Vitro, 2009, 23, 1372-1379.
K Schirmer, K Tanneberger, NI Kramer, D Voelker, S Scholz, C Hafner, LEJ Lee, NC Bols, JLM Hermens. Developing a list of reference chemicals for testing alternatives to whole fish toxicity tests. Aquatic Toxicology 2008, 90, 128-137.
Lee L., Dayeh V.R., Schirmer K. and Bols N.C. (2008). Fish cell lines as rapid and inexpensive screening and supplemental tools for whole effluent testing. Integrated Environmental Assessment and Management. 4, 372-374.
Lee L., Dayeh V.R., Schirmer K. and Bols N.C. (2009). Applications and potential uses of fish gill cell lines:
examples with RTgill-W1. In Vitro Cellular & Developmental Biology – Animal. 45, 127-134.
Development of a strategy to substitute acute fish toxicity tests by Kristin Schirmer, Katrin Tanneberger, Nynke Kramer, Doris Voelker, Stefan Scholz, Niels C. Bols, Lucy E.J. Lee, Christoph Hafner and Joop L.M. Hermens