| Autor: |
Mizumachi, Hideyuki, Watanabe, Mika, Ikezumi, Mayu, Kajiwara, Michika, Yasuda, Michiyo, Mizuno, Makoto, Imai, Noriyasu, Sakuma, Megumi, Shibata, Momoko, Watanabe, Shin‐ichi, Motoyama, Junko, Basketter, David, Eskes, Chantra, Hoffmann, Sebastian, Lehmann, David M., Ashikaga, Takao, Sozu, Takashi, Takeyoshi, Masahiro, Suzuki, Sho, Miyazawa, Masaaki |
| Předmět: |
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| Zdroj: |
Journal of Applied Toxicology; Apr2024, Vol. 44 Issue 4, p510-525, 16p |
| Abstrakt: |
The Epidermal Sensitization Assay (EpiSensA) is a reconstructed human epidermis (RhE)‐based gene expression assay for predicting the skin sensitization potential of chemicals. Since the RhE model is covered by a stratified stratum corneum, various kinds of test chemicals, including lipophilic ones and pre‐/pro‐haptens, can be tested with a route of exposure akin to an in vivo assay and human exposure. This article presents the results of a formally managed validation study of the EpiSensA that was carried out by three participating laboratories. The purpose of this validation study was to assess transferability of the EpiSensA to new laboratories along with its within‐ (WLR) and between‐laboratory reproducibility (BLR). The validation study was organized into two independent stages. As demonstrated during the first stage, where three sensitizers and one non‐sensitizer were correctly predicted by all participating laboratories, the EpiSensA was successfully transferred to all three participating laboratories. For Phase I of the second stage, each participating laboratory performed three experiments with an identical set of 15 coded test chemicals resulting in WLR of 93.3%, 93.3%, and 86.7%, respectively. Furthermore, when the results from the 15 test chemicals were combined with those of the additional 12 chemicals tested in Phase II of the second stage, the BLR for 27 test chemicals was 88.9%. Moreover, the predictive capacity among the three laboratories showed 92.6% sensitivity, 63.0% specificity, 82.7% accuracy, and 77.8% balanced accuracy based on murine local lymph node assay (LLNA) results. Overall, this validation study concluded that EpiSensA is easily transferable and sufficiently robust for assessing the skin sensitization potential of chemicals. EpiSensA is an in vitro skin sensitization test method based on gene expression of Rhe. This article presents the results of a formal validation study for assessing its transferability and reliability. The EpiSensA was successfully transferred to three participating laboratories. Furthermore, each laboratory performed three experiments with 15 coded test chemicals resulting in within‐laboratory reproducibility of 86.7 to 93.3%, respectively. Moreover, the between‐laboratory reproducibility for 27 chemicals was 88.9%. Overall, EpiSensA was a sufficiently transferable and robust method. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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