[Prediction of LD50 values by cell culture]

Alternative approaches to toxicity tests with animals-more precisely defined as complementary methods-serve for reducing the number of animal experiments. The determination of cytotoxicity with cell cultures could be an important complementary method to get more information about a general basal toxicity of a substance in an organism during the course of an acute toxicity experiment. We employed the endothelial cell line BKEz-7 in a general (i.e. nonspecific) cytotoxicity test. As a quantitative marker of cytotoxic effects we determined the inhibition concentration for a fifty per cent reduction of the cell number per culture (IC50). the IC50 values of 28 compounds were compared with the corresponding LD50 values in the acute toxicity experiments. In these comparisons we included the determination of the lethality index (LI = IC50/LD50), the correlation analyses and the application of a single linear regression model. The following results were obtained. Between the IC50 and LD50 values a positive correlation exists at the significance level 1 - alpha = 0.95. After plotting the regression line in a coordinate system, a novel graphic prediction of LD50 estimations is possible with a relatively high accuracy. On the basis of tenfold steps of concentrations a new scale of cytotoxicity was attributed to the internationally employed classification of LD50. In the cytotoxicity test with the cell line BKEz-7 a broad spectrum of substance classes can be tested. The cytotoxicity test and the comparison of IC50 and LD50 p.o. as described here contribute to reduce the number of animals in the acute toxicity experiments.