THE CFTA EVALUATION OF ALTERNATIVES PROGRAM - AN EVALUATION OF IN-VITRO ALTERNATIVES TO THE DRAIZE PRIMARY EYE IRRITATION TEST - (PHASE-III) SURFACTANT-BASED FORMULATIONS

The CTFA Evaluation of Alternatives Program is an evaluation of the re lationship between data from the Draize primary eye irritation test an d comparable data from a selection of promising in vitro eye irritatio n tests. In Phase III,data from the Draize test and 41 in vitro endpoi nts on 25 representative surfactant-based personal care formulations w ere compared. As in Phase I and Phase II, regression modelling of the relationship between maximum average Draize score (MAS) and in vitro e ndpoint was the primary approach adopted for evaluating in vitro assay performance. The degree of confidence in prediction of MAS for a give n in vitro endpoint is quantified in terms of the relative widths of p rediction intervals constructed about the fitted regression curve. Pre diction intervals reflect not only the error attributed to the model b ut also the material-specific components of variation in both the Drai ze and the in vitro assays. Among the in vitro assays selected for reg ression modelling in Phase III, the relationship between MAS and in vi tro score was relatively well defined. The prediction bounds on MAS we re most narrow for materials at the lower or upper end of the effectiv e irritation range (MAS = 0-45), where variability in MAS was smallest . Thus, the confidence with which the MAS of surfactant-based formulat ions is predicted is greatest when MAS approaches zero or when MAS app roaches 45 (no comment is made on prediction of MAS > 45 since extrapo lation beyond the range of observed data is not possible). No single i n vitro endpoint was found to exhibit relative superiority with regard to prediction of MAS. Variability associated with Draize test outcome (e.g. in MAS values) must be considered in any future comparisons of in vivo and in vitro test results if the purpose is to predict in vivo response using in vitro data.