The use of in vitro cytotoxicity measurements in QSAR methods for the prediction 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 the EC risk phrases R34 and R35) of acids to parameters that model their skin permeability and cytotoxicity. Skin permeability was modelled by log(octanol/water partition coefficient), molecular volume and melting point, while the cytotoxicity of the acids was accounted for by their pK(a), values and the in vitro cytotoxicity of their sodium salts towards Swiss mouse embryo 3T3 cells. The dataset was analysed using principal components and neural network analysis. The classification predictions from both QSAR methods were in agreement with those in the training set for 26 of the 27 acids. The methods provide useful procedures for the prediction of the skin corrosivity potentials of severely corrosive acids, which avoid the use of experimental animals and demonstrate the value of in vitro cytotoxicity parameters as inputs for QSAR analysis.
Barratt
M D
MD
Unilever Environmental Safety Laboratory, Colworth House, Sharnbrook, Bedford MK44 1LQ, UK.
Dixit
M B
MB
Jones
P A
PA