Multiple Computer Automated Structure Evaluation Methodology as an Alternative toIn VivoEye Irritation Testing

Abstract

The Multiple Computer Automated Structure Evaluation (Multi-CASE) methodology was applied to the semi-quantitative analysis of eye irritation potential of 186 organic chemicals. The resulting expert dictionary of substructural attributes indicates that the following functionalities are linked to eye irritation potential: carboxylate and sulphonate groups in anionic surfactants, phenolic moieties in non-ionic surfactants, amino groups, halogenated and unsaturated structures, anhydrides and epoxides. Ester groups were recognised as having a low irritation potential. The Multi-CASE program successfully predicted a priori the eye irritation potential of: 1) 21 individual chemicals; 2) chemical mixtures such as coconut oil, hydrogenated castor oil, rice bran, eucalyptus oils and potassium alginate; and 3) polymers,’ including polyvinyl alcohols, polyvinyl butyral, polyvinyl pyrrolidone, corn starch and nylon. It was found that the structure of the repeat units together, and not that of the individual monomers, is the best predictor of the eye irritation potential of the corresponding polymers. It appears that the repeat units of polymers dilute out the irritation potential of terminal groups normally expected to contribute significant irritation potential to chemicals of lower molecular weight.The Multi-CASE eye irritation model can be used for: 1) in vitro prescreening for eye irritation potential; and 2) design and modification of chemicals when low eye irritation potential is important.