Definition of the Applicability Domain of the Short Time Exposure (STE) Test for Predicting the Eye Irritation of Chemicals

Abstract

The Short Time Exposure (STE) test is a simple and easy-to-perform in vitro eye irritation test, that uses the viability of SIRC cells (a rabbit corneal cell line) treated for five minutes as the endpoint. In this study, our goal was to define the applicability domain of the STE test, based on the results obtained with a set of 113 substances. To achieve this goal, chemicals were selected to represent both different chemical classes and different chemical properties, as well as to cover, in a balanced manner, the categories of eye irritation potential according to the Globally Harmonised System (GHS). Accuracy analysis indicated that the rates of false negatives for organic/inorganic salts (75.0%), hydrocarbons (33.3%) and alcohols (23.5%) were high. Many of the false negative results were for solid substances. It is noteworthy that no surfactant resulted in a false negative result in the STE test. Further examination of the physical property data and performance showed a significant improvement in the predictive accuracy, when substances with vapour pressures over 6kPa were excluded from the analyses. Our results indicate that several substances — i.e. certain solids such as salts, alcohols, hydrocarbons, and volatile substances with a vapour pressure over 6kPa — do not fall within the applicability domain of the STE test. Overall, we are encouraged by the performance and improved accuracy of the STE test.

Expansion of the applicability domain for highly volatile substances on the Short Time Exposure test method and the predictive performance in assessing eye irritation potential

“…The STE test method has been validated by the Japanese Society for Alternatives to Animal Experiments and the Japanese Center for the Validation of Alternative Methods (Sakaguchi et al, 2011;Kojima et al, 2013). Furthermore, its applicability domain was determined via a peer review organized by the Interagency Coordinating Committee on the Validation of Alternative Methods (Hayashi et al, 2013;NICEATM, 2013). Although the STE test method is used to identify GHS NC for chemicals, the exceptions are as follows: i) highly volatile substances (vapor pressure > 6 kPa, 25°C) and ii) solids other than surfactants.…”