COMPARISON OF LOW-VOLUME - DRAIZE AND IN-VITRO EYE IRRITATION TEST DATA - II - OIL WATER EMULSIONS/

The second phase in a series of investigations of the relationship bet ween low volume eye test (LVET) data, Draize eye irritation test data, and comparable data from in vitro eye irritation lest protocols is pr esented. These investigations utilize Draize eye test and in vitro end point data generated previously as part of the CTFA Evaluation of Alte rnatives Program. LVET data were generated de novo using the same 18 r epresentative oil/water based personal-care formulations. In general, these formulations were minimally to mildly irritating; only three wer e classified as moderate eye irritants. The linear correlation between maximum average score as determined by the Draize test (MAS) and the LVET (LVET-MAS) was 0.85; LVET-MAS values were typically about half th e corresponding MAS values. Comparison of in vitro assay performance w ith that of the LVET was determined by statistical analysis of the rel ationship between LVET-MAS and each in vitro endpoint. Regression mode lling was the primary means of enabling such a comparison. the objecti ve being to predict LVET-MAS for a given test material (and to place u pper and lower 95% prediction bounds on the range in which the LVET-MA S is anticipated to fall with high probability) based on observation o f an in vitro score for that material. The degree of confidence in pre diction is quantified in terms of the relative widths of pre diction i ntervals constructed about the fitted regression curves. Sixteen endpo ints were shown to have the greatest agreement with the LVET (all but two were selected for modelling when compared with the Draize procedur e). While the lower maximum average scores values (compared with the D raize test) in the LVET led to lower variability in LVET-MAS compared to MAS, the upper and lower bounds on predicted LVET-MAS values condit ional on observed in vitro scores were still wide. Because there was o verlap in the range of scores determined by the prediction bounds for many formulations, each of the selected endpoints was frequently unabl e to distinguish between test formulations in terms of statistically d ifferent predicted LVET-MAS values. In summary, none of the in vitro e ndpoints evaluated were able to reliably predict values of LVET-MAS am ong the set of oil/water emulsions considered here. (C) 1998 Elsevier Science Ltd. All rights reserved.