title: Second-phase validation study of short time exposure test for assessment of eye irritation potency of chemicals.
abstract: 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).
authors.affiliation: Japanese Center for Validation of Alternative Methods, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan. h-kojima@nihs.go.jp
authors.forename: Hajime
authors.initials: H
authors.lastname: Kojima
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hayashi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sakaguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Omori
authors.forename: Takuya
authors.initials: T
authors.lastname: Otoizumi
authors.forename: Takashi
authors.initials: T
authors.lastname: Sozu
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kuwahara
authors.forename: Takumi
authors.initials: T
authors.lastname: Hayashi
authors.forename: Mayumi
authors.initials: M
authors.lastname: Sakaguchi
authors.forename: Akemi
authors.initials: A
authors.lastname: Toyoda
authors.forename: Haruka
authors.initials: H
authors.lastname: Goto
authors.forename: Shinichi
authors.initials: S
authors.lastname: Watanabe
authors.forename: Kyoko
authors.initials: K
authors.lastname: Ahiko
authors.forename: Tsuneaki
authors.initials: T
authors.lastname: Nakamura
authors.forename: Takashi
authors.initials: T
authors.lastname: Morimoto
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D002460:Cell Line; D003315:Cornea / Q000166:cytology / Q000187:drug effects*; D007509:Irritants / Q000633:toxicity*; D011817:Rabbits; D015203:Reproducibility of Results; D023382:Toxicity Tests, Acute / Q000379:methods*
chemical_list: D007509:Irritants
keywords: Alternative method; Eye irritation; GHS; SIRC cells; STE; Validation