Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute (ITRI), Taiwan, ROC.
Japanese Center for the Validation of Alternative Methods (JaCVAM), National Institute of Health Sciences (NIHS), Japan.
Toxicol In Vitro. 2021 Sep;75:105197. doi: 10.1016/j.tiv.2021.105197. Epub 2021 May 29.
Following the global trend of reducing animal testing, various reconstructed human epidermis (RHE) models for skin irritation test (SIT) have been developed, verified, validated and included in OECD TG 439. We developed a new RHE called EPiTRI and a SIT method using EPiTRI (EPiTRI-SIT model) following the OECD guidelines. EPiTRI possesses morphological, biochemical and physiological properties similar to human epidermis with well-differentiated multilayered viable cells with barrier function. The EPiTRI-SIT model was tested for 20 reference chemicals in Performance Standard of OECD TG 439 (GD 220), showing good predictive capacity with 100% sensitivity, 70% specificity and 85% accuracy. EPiTRI had sensitivity in detecting di-n-propyl disulphate, as an irritant chemical (UN GHS Category 2), whereas most validated reference methods detected it as a non-irritant. An international validation study of EPiTRI-SIT was conducted in four laboratories to confirm the within- and between-laboratory reproducibility, as well as predictive capacity. The phase I/II within-laboratory and between-laboratory reproducibility was 100%/95% and 95%, respectively. The overall sensitivity, specificity and accuracy of EPiTRI-SIT was 96%, 70% and 83%, respectively, which fulfilled the OECD criteria. Thus, EPiTRI, meets the criteria of Performance Standards of OECD TG 439 (GD 220) and is suitable for screening irritating chemicals in vitro.
随着全球减少动物试验的趋势，已经开发、验证、确认了各种用于皮肤刺激试验（SIT）的重建人体表皮（RHE）模型，并将其纳入了 OECD TG 439。我们按照 OECD 指南开发了一种新的 RHE，称为 EPiTRI，并开发了一种使用 EPiTRI 的 SIT 方法（EPiTRI-SIT 模型）。EPiTRI 具有与人类表皮相似的形态、生化和生理特性，具有具有屏障功能的分化良好的多层活细胞。EPiTRI-SIT 模型在 OECD TG 439 的性能标准（GD 220）中对 20 种参考化学品进行了测试，具有良好的预测能力，敏感性为 100%，特异性为 70%，准确性为 85%。EPiTRI 对二丙基二硫硫酸盐（UN GHS 类别 2 的刺激性化学品）具有敏感性，而大多数经过验证的参考方法将其检测为非刺激性化学品。在四个实验室中进行了 EPiTRI-SIT 的国际验证研究，以确认实验室内部和实验室之间的重现性以及预测能力。第一阶段/第二阶段实验室内部和实验室之间的重现性分别为 100%/95%和 95%。EPiTRI-SIT 的整体敏感性、特异性和准确性分别为 96%、70%和 83%，符合 OECD 标准。因此，EPiTRI 符合 OECD TG 439 性能标准（GD 220）的标准，适合用于体外筛选刺激性化学品。
