THE CTFA EVALUATION OF ALTERNATIVES PROGRAM - AN EVALUATION OF IN-VITRO ALTERNATIVES TO THE DRAIZE PRIMARY EYE IRRITATION TEST - (PHASE-II)OIL WATER EMULSIONS/

The Cosmetic, Toiletry and Fragrance Association (CTFA) Evaluation of Alternatives Program is an evaluation of the relationship between Drai ze ocular safety test data and comparable data from a selection of in vitro tests. In Phase II, 18 representative oil/water-based personal-c are formulations were subjected to the Draize primary eye safety test and 30 in vitro assay protocols (14 different types of in vitro endpoi nts were evaluated; the remainder were protocol variations). Correlati on of in vitro with in vivo data was evaluated using analysis of sensi tivity/specificity and statistical analysis of the relationship betwee n maximum average Draize score (MAS) and in vitro endpoint. Regression modelling is the primary approach adopted in the CTFA Program for eva luating in vitro assay performance. The objective of regression analys is is to predict MAS for a given test material (and to place upper and lower prediction interval bounds on the range in which the MAS is ant icipated to fall with high probability) conditional on observing an in vitro assay score for that material. The degree of confidence in pred iction is quantified in terms of the relative widths of prediction int ervals constructed about the fitted regression curves: the narrower th e prediction interval, the more predictive of the Draize score is the in vitro test result. 16 assays were shown to have the greatest agreem ent with the Draize procedure and were therefore selected for regressi on analysis. Based on the magnitude of the 95% prediction bounds of ea ch of the 16 selected assays over the range of test data, it may be in ferred that prediction of MAS values from experimentally determined in vitro scores is more accurate for oil/water-based formulations with l ower rather than higher irritancy potential. The assays selected for m odelling in Phase II generally exhibited weaker relationships with MAS than those selected in Phase I (evaluated using hydroalcoholic formul ations), even though several assays were common to both Phases.