PHASE I SAR ESTIMATION OF SKIN AND EYE IRRITATION

THIS PROPOSAL DEALS WITH THE DEVELOPMENTOF STRUCTURE ACTIVITY EQUATIONS (MODELS) FOR THE DRAIZE SKIN AND EYE IRRITANCY TESTS. THE APPLICANT HAS PREVIOUSLY DEVELOPED SUCH MODELS FOR RAT ORAL LD(50), MUTAGENICITY, CARCINOGENICITY, TERATOGENICITY, AND BIODEGRADABILITY. THE PRINCIPLES USED IN THE DEVELOPMENT OF THESE MODELS ARE TO BE APPLIED TO THE DEVELOPMENT OF SIMILAR MODELS FOR THE DRAIZE TESTS. IN THESE MODELS A SET OF CHEMICALS FOR WHICH THE ENDPOINTS HAVE BEEN MEASURED ARE USED TO FORM THE BASIS OF REGRESSION EQUATIONS. THE INDEPENDENT PARAMETERS INCLUDESUBSTRUCTURAL FRAGMENTS, AND PHYSICAL PARAMETERS SUCH AS OCTANOL-WATER PARTITION COEFFICIENT, MOLECULAR WEIGHT, MOLECULAR AREA AND VOLUME, MOLECULAR CONNECTIVITY INDICES, ETC. THE MAJORITY OF THE DATA FOR THE MODEL WILL BE DERIVEDFROM RTECS (REGISTRY OF TOXIC EFFECTS OF CHEMICAL SUBSTANCES), WITH THE REMAINING DATA BEING OBTAINED FROM THEU. S. ARMY AND A DIRECETED SURVEY OF THE LITERATURE.