[Prediction of acute toxicity]
The updated register of cytotoxicity data (RCD) is containing 361 chemicals with a total of 1912 IC50 values, for each of which a mean IC50 (IC50) has been calculated. In addition, the RCD is containing oral and i.v. LD50 values for rats and mice from the NIOSH resister RTECS. For 347 of the data pairs IC50/LD50 p.o. and for 148 of the data pairs IC50/LD50 i.v. linear standard regression lines have been calculated, which allow to predict an approximative LD50 value from a given IC50. For a group of 26 neurotropic agents documented in the RCD the prediction of LD50 values from IC50 data was surprisingly good. This suggests that even for neurotropic agents there is a sufficient positive correlation between in vitro and in vivo toxicity. The unexpected result is discussed with respect to basal cytotoxicity which seems to be reflected by IC50 and which is related to basic functions of the cells, as e.g. proliferation, DNA- and protein synthesis, rather than to specific endpoints of neurotoxicity. The results obtained with 26 neurotropic agents support the concept that acute toxicity in vivo can sufficiently be predicted from the data of the updated RDC. An attempt is made to predict the approximate LD50 values, both p.o. and i.v., data from IC50 values of the RDC for an established neurotropic agent with insufficient acute in vivo toxicity data.
Halle
Willi
W
Forschungsinstitut für Molekulare Pharmakologie im Forschungsverbund Berlin e.V., D-Berlin.
Spielmann
Horst
H