[Reduction of the number of animals used for the classification of the acute toxicity of chemicals by taking into account cytotoxicity data from the registry of cytotoxicity (RC)] [Article in German]

Abstract

Using Cytotoxicity data a new classification procedure is introduced which will allow to allocate chemicals to the four toxicity classes for acute oral toxicity according to EU regulation. Simultaneously, the new procedure allows to reduce animals in experiments for determination of these four toxicity classes. The cytotoxicity data estimated from in vitro cultivated mammalian cell lines were taken from the "Registry of Cytotoxicity" (RC) in which the mean IC50 (IC50x) of 347 chemicals are stored as well as the acute oral toxicity data (LD50) for rats and mice taken from NIOSH registry. As we have been used to calculate a standard regression line for predicting the dosage range of acute oral toxicity in the two species. The maximum, mean and minimum dosages of oral toxicity were predicted from the RC data and furthermore, these dosages were the basis for allocating chemicals into the four classes of acute oral toxicity defined by the EU. The accuracy for predicting the toxicity classes of the 347 chemicals registered in the RC in comparison to the toxicity classes of the corresponding NIOSH LD50 values amounts 80 percent to 88 percent. We have developed a tier testing strategy for the classification of chemicals into EU toxicity classes which takes into account the cytotoxicity data as predicted mean LD50 in connection with the protocol steps described in Acute Toxic Class (ATC) method. Compared with the ATC method the new combined RC-ATC procedure will allow to reduce animal numbers for allocating chemicals to the EU toxicity classes by about 30 percent. We suggest to validate the RC-ATC procedure in order to achieve regulatory acceptance at the international level.