THE USE OF IN-VITRO CYTOTOXICITY MEASUREMENTS IN QSAR METHODS FOR THEPREDICTION OF THE SKIN CORROSIVITY POTENTIAL OF ACIDS

Quantitative structure-activity relationships (QSAR) methods have been derived that relate the severity of skin corrosivity (designated by t he EC risk phrases R34 and R35) of acids to parameters that model thei r skin permeability and cytotoxicity. Skin permeability was modelled b y log(octanol/water partition coefficient), molecular volume and melti ng point, while the cytotoxicity of the acids was accounted for by the ir pK(a) values and the in vitro cytotoxicity of their sodium salts to wards Swiss mouse embryo 3T3 cells. The dataset was analysed using pri ncipal components and neural network analysis. The classification pred ictions from both QSAR methods were in agreement with those in the tra ining set for 26 of the 27 acids. The methods provide useful procedure s for the prediction of the skin corrosivity potentials of severely co rrosive acids, which avoid the use of experimental animals and demonst rate the value of in vitro cytotoxicity parameters as inputs for QSAR analysis. Copyright (C) 1996 Elsevier Science Ltd