Validation of the Epi2SensA Method Using the EpiDerm™ Model for Skin Sensitization Testing Under OECD TG442D

使用 EpiDerm™ 模型验证 Epi2SensA 方法在 OECD TG442D 下的皮肤致敏性测试应用

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Abstract

The Epi2SensA method is a method similar to the validated EpiSensA assay for assessing the skin sensitization potential of chemicals. The Epi2SensA protocol includes adaptation (changes to exposure conditions and the controls) for using an alternative reconstructed human epidermis (RhE) model, the EpiDerm™ model. The interlaboratory validation study evaluated the reliability and predictive capacity of Epi2SensA according to OECD Performance Standards. Four laboratories (Mattek, Now Part of Sartorius, Eurofins Munich, Burleson Research Technologies, Inc., and Food and Drug Safety Center) conducted blinded testing of 20 coded reference substances representing various chemical categories and sensitization potencies. Statistical analysis using modified acceptance criteria (a 60% cell viability threshold) and a modified prediction model (requiring at least two positive gene markers) demonstrated substantially improved performance compared to the original EpiSensA criteria. The between-laboratory reproducibility (BLR) was 85%, the average within-laboratory reproducibility (WLR) was 83.3%, and the average predictivity parameters were 88.1% for sensitivity, 88.9% for specificity, and 88.3% for accuracy. Epi2SensA achieved performance metrics comparable to the validated reference method (EpiSensA), supporting regulatory acceptance of the Epi2SensA assay using the EpiDerm™ model (Mattek Corporation, Now Part of Sartorius, Ashland, MA, USA) as an alternative RhE source for OECD TG 442D skin sensitization testing.

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