Second-phase validation study of short time exposure test for assessment of eye irritation potency of chemicals

• Published in: Toxicology in vitro 2013-09, Vol.27 (6), p.1855-1869
• Main Authors: Kojima, Hajime, Hayashi, Kazuhiko, Sakaguchi, Hitoshi, Omori, Takashi, Otoizumi, Takuya, Sozu, Takashi, Kuwahara, Hirofumi, Hayashi, Takumi, Sakaguchi, Mayumi, Toyoda, Akemi, Goto, Haruka, Watanabe, Shinichi, Ahiko, Kyoko, Nakamura, Tsuneaki, Morimoto, Takashi
• Format: Article
• Language: English
• Subjects: Alternative method; Animal Testing Alternatives; Animals; Cell Line; Cornea - cytology; Cornea - drug effects; Eye irritation; GHS; Irritants - toxicity; Rabbits; Reproducibility of Results; SIRC cells; STE; Toxicity Tests, Acute - methods; Validation
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2013.05.013

•The STE (Short Time Exposure) test can assess eye irritation potency.•The STE is a cytotoxicity test using SIRC cells following a 5 min chemical exposure.•The STE test can assess the corrosive or severe ocular irritant.•The STE test can assess the non-irritant for limited types of test substances. A Short Time Exposure (STE) test is a cytotoxicity test that uses SIRC cells (rabbit corneal cell line) to assess eye irritation potency following a 5-min chemical exposure. This second-phase validation study assessed the predictive capacity of the STE test using 40 coded test substances at three laboratories. A Validation Management Team (VMT) then evaluated the predictivity of the STE test for United Nation (UN) Globally Harmonized System (GHS) categories using 63 test substances including the results of the first-phase validation study. The STE test can assess not only the severe or corrosive ocular irritants (corresponding to the UN GHS Category 1) but also non-irritant (corresponding to UN GHS Non Category) from other toxicity classes, especially for limited types of test substances. The predictivity by STE test, however, was insufficient for identification of UN GHS categories (Category 1, Category 2, or Non Category). These results suggest that the STE test can be recommended as an initial step in a top-down approach to identification of severe irritants and test substances that require classification for eye irritation (UN GHS Category 1) as well as an initial step in a bottom-up approach to identification of test substances that do not require classification for eye irritation (UN GHS Non Category) from other toxicity classes, especially for limited types of test substances. On the other hand, the STE test is not considered adequate for the identification of mild or moderate irritants (i.e., UN GHS Categories 2A and 2B) and severe irritants (UN GHS Category 1).