title: Prevalidation trial for a novel in vitro eye irritation test using the reconstructed human cornea-like epithelial model, MCTT HCE™.
abstract: Here, we report the results of a prevalidation trial for an in vitro eye irritation test (EIT) using the reconstructed human cornea-like epithelium, MCTT HCE™. The optimal cutoff to determine irritation in the prediction model was established at 35% with the receiver operation characteristics(ROC) curve for 126 substances. Within-lab(WL) and between-lab(BL) reproducibility was tested for 20 reference substances by 3 participating laboratories. Viability data described by mean±SD or ±1/2 difference between duplicate wells, and scatter plots, demonstrated the WL/BL consistency. WL/BL concordance with the binary decision, whether non-irritant or irritant was estimated to be 85-95% and 95%, respectively. WL/BL reproducibility of viability data was further supported by a strong correlation(ICC, r>0.9). WL/BL agreement of binary decisions was also examined by Fleiss' Kappa statistics, which showed a strong level of agreement (>0.78), nevertheless weaker than the reproducibility of the viability. The EIT with MCTT HCE™ exhibited a sensitivity of 82.2% (60/73), a specificity of 81.1% (43/53), and an accuracy of 81.8% (103/126) for 126 reference substances (for liquids; a sensitivity of 100% (47/47), a specificity of 70.6% (24/34), and an accuracy of 87.7% (71/81), and for solids, a sensitivity of 50% (13/26), a specificity of 100% (19/19), and an accuracy of 71.1% (32/45), suggesting that the accuracy is satisfactory but the sensitivity needs improvement, which shall be addressed through correcting the poor sensitivity for solid substances in future full validation trials.
authors.affiliation: College of Pharmacy, Ewha Womans University, Seoul 03760, Republic of Korea.
authors.forename: Hyeri
authors.initials: H
authors.lastname: Yang
authors.affiliation: College of Pharmacy, Ewha Womans University, Seoul 03760, Republic of Korea.
authors.forename: Da-Eun
authors.initials: DE
authors.lastname: Kim
authors.affiliation: AmorePacific Corp. R&D Center, Yongin 17074, Republic of Korea.
authors.forename: Won-Hee
authors.initials: WH
authors.lastname: Jang
authors.affiliation: AmorePacific Corp. R&D Center, Yongin 17074, Republic of Korea.
authors.forename: Susun
authors.initials: S
authors.lastname: An
authors.affiliation: AmorePacific Corp. R&D Center, Yongin 17074, Republic of Korea.
authors.forename: Sun-A
authors.initials: SA
authors.lastname: Cho
authors.affiliation: Pharmacology Efficacy Team, Biotoxtech Co., Ltd., Osong 18115, Republic of Korea.
authors.forename: Mi-Sook
authors.initials: MS
authors.lastname: Jung
authors.affiliation: Pharmacology Efficacy Team, Biotoxtech Co., Ltd., Osong 18115, Republic of Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Healthcare R&D Center, Korea Testing & Research Institute, Hwa-Soon 58141, Republic of Korea.
authors.forename: Kyung-Wook
authors.initials: KW
authors.lastname: Yeo
authors.affiliation: Healthcare R&D Center, Korea Testing & Research Institute, Hwa-Soon 58141, Republic of Korea.
authors.forename: Sang Bum
authors.initials: SB
authors.lastname: Koh
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 38541, Republic of Korea.
authors.forename: Tae-Cheon
authors.initials: TC
authors.lastname: Jeong
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 38541, Republic of Korea.
authors.forename: Mi-Jeong
authors.initials: MJ
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul 06911, Republic of Korea.
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Chun
authors.affiliation: R&D Institute, Biosolution Co., Ltd., Seoul 01811, Republic of Korea.
authors.forename: Su-Hyon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Ewha Womans University, Seoul 03760, Republic of Korea. Electronic address: kmlim@ewha.ac.kr.
authors.forename: Kyung-Min
authors.initials: KM
authors.lastname: Lim
authors.affiliation: College of Pharmacy, Ewha Womans University, Seoul 03760, Republic of Korea. Electronic address: sjbae@ewha.ac.kr.
authors.forename: SeungJin
authors.initials: S
authors.lastname: Bae
mesh_terms: D000826:Animal Testing Alternatives; D002470:Cell Survival / Q000187:drug effects; D019573:Epithelium, Corneal / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007509:Irritants / Q000633:toxicity*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D007509:Irritants
keywords: Eye irritation test; MCTT HCE™; Predictive capacity; Reproducibility; Statistical analysis