title: Two-stage bottom-up tiered approach combining several alternatives for identification of eye irritation potential of chemicals including insoluble or volatile substances.
abstract: For the assessment of eye irritation, one alternative test may not completely replace the rabbit Draize test. In the present study, we examined the predictive potential of a tiered approach analyzing the results from several alternatives (i.e., the Short Time Exposure (STE) test, the EpiOcular assay, the Hen's Egg Test-Chorioallantoic Membrane (HET-CAM) assay and the Bovine Corneal Opacity and Permeability (BCOP) assay) for assessing Globally Harmonized System (GHS) eye irritation categories. Fifty-six chemicals including alcohols, surfactants, and esters were selected with a balanced GHS category and a wide range of chemical classes. From a standpoint of both assessable sample numbers and predictive accuracy, the more favorable tiered approach was considered to be the two-stage bottom-up tiered approach combining the STE test, the EpiOcular assay followed by the BCOP assay (accuracy 69.6%, under prediction rate 8.9%). Moreover, a more favorable predictive capacity (accuracy 71.4%, under prediction rate 3.6%) was obtained when high volatile alcohols/esters with vapor pressures >6 kilopascal (kPa) at 25°C were evaluated with EpiOcular assay instead of the STE test. From these results, the two-stage bottom-up tiered approach combining the STE test, the EpiOcular assay followed by the BCOP assay might be a promising method for the classification of GHS eye irritation category (Not classified (NC), Category 2 (Cat. 2), and Category 1 (Cat. 1)) for a wide range of test chemicals regardless of solubility.
authors: Safety Science Research Laboratories, Kao Corporation, 2606 Akabane, Ichikai-Machi, Haga-Gun, Tochigi 321-3497, Japan. hayashi.kazuhiko@kao.co.jp
authors: Kazuhiko
authors: K
authors: Hayashi
authors: Taeko
authors: T
authors: Mori
authors: Takayuki
authors: T
authors: Abo
authors: Kenichi
authors: K
authors: Ooshima
authors: Takumi
authors: T
authors: Hayashi
authors: Tomoko
authors: T
authors: Komano
authors: Yutaka
authors: Y
authors: Takahashi
authors: Hitoshi
authors: H
authors: Sakaguchi
authors: Akihiko
authors: A
authors: Takatsu
authors: Naohiro
authors: N
authors: Nishiyama
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D002417:Cattle; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D049033:Chorioallantoic Membrane / Q000187:drug effects / Q000473:pathology; D003315:Cornea / Q000187:drug effects / Q000473:pathology; D003318:Corneal Opacity / Q000139:chemically induced / Q000473:pathology; D005123:Eye / Q000187:drug effects*; D007509:Irritants / Q000145:classification / Q000633:toxicity*; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012107:Research Design; D012995:Solubility; D023382:Toxicity Tests, Acute / Q000379:methods*; D055549:Volatile Organic Compounds / Q000633:toxicity*; D014835:Volatilization
chemical_list: D007509:Irritants; D055549:Volatile Organic Compounds