Evaluation of the relevance of selected in vitro toxicity test systems for acute systemic toxicity

By Seibert, H. - Gulden, M. - Kolossa, M. - Schepers, G.

Progress in the implementation of in vitro methods in testing procedures for non-genetic toxicity is limited by poor or missing validation of the various approaches. Many efforts have focused on determinations of general cytotoxicity in vitro using proliferating, nondifferentiated cell lines. The aim of our present studies is to evaluate the relevance to acute systemic toxicity of three in vitro systems using differentiated mammalian cells (bovine spermatozoa, primary cultured rat hepatocytes, primary cultured rat skeletal muscle cells) and also one in vitro system which uses a continuous cell line (BALB/C 3T3 cells). This combination of in vitro systems covers various aspects of cellular toxicity and permits the determination of the intrinsic activity of chemicals with respect to general cytotoxicity, selective cytotoxicity and interference with selected cell-specific functions. In order to contribute to the establishment of a basis for the selection of methods to be included in test batteries in the future, we are contributing to the MEIC programme. In the present communication, results for the first ten chemicals of the MEIC list are presented and discussed.