A QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP (QSAR) FOR A DRAIZE EYE IRRITATION DATABASE

A collection of data on the Draize rabbit eye test (Cronin et al., 199 4) has been analysed using a set of physicochemical descriptors that w e have previously put forward. These descriptors are compound (or solu te) parameters as follows: R-2 is an excess molar refraction, pi(2)(H) is the polarizability/dipolarity Sigma alpha(2)(H) and Sigma beta(2)( H) are the effective hydrogen bond acidity and basicity, and logL(16) is a descriptor where L-16 is the vapour-hexadecane solubility at 25 d egrees C. When applied to Draize eye scores (DESs) for 38 pure bulk li quids, a very poor equation was obtained. However, when the DES values were correlated as log(DES/P-o), where P-o is the liquid vapour press ure, an excellent equation was found. On transforming the calculated l og(DES/P-o) values back to calculated DES values, there was good agree ment with the original DES values. It is suggested that the DES/P-o va lues refer to transfer of the irritant from the vapour phase to the bi ophase, and that the success of the present treatment demonstrates tha t for the pure liquids studied, a major factor in the Draize eye test is simply the transfer of the liquid (or the vapour) to the biological system. (C) 1998 Elsevier Science Ltd. All rights reserved.