A novel statistical approach for the evaluation of comet assay data

The present study forms part of a weight-of-evidence framework including genotoxicological studies in the upper Danube River basin, which aim at elucidating the reasons for the decline in fish catch. The major focus of this paper is the assessment of genotoxicity of sediments from the Danube River basin by use of the comet assay with RTL-W1 cells and with embryos of zebrafish (Danio rerio). A frequently discussed question in this type of approach is how to aggregate and compare the data obtained from genotoxicity testing. There is a need to develop mathematical method combining the information from dose-response curves and level of effectiveness (maximum genotoxic effect). For comparison and ranking of the genotoxic potential of samples from different locations along the Danube River, several methods based on EC50, Lowest Observed Effect Concentration (LOEC), and maximum induction factor were compared with respect to their validity. An evaluation system termed the "3-step analysis" was developed to facilitate consideration of a maximum number of aspects of the raw data. The so-called "concentration-dependent induction factor" (CDI) introduces an index for a straightforward, precise and realistic assessment of the genotoxic potential of any kind of field sample or genotoxic agent.