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In Vitro Prediction of Skin-Sensitizing Potency Using the GARDskin Dose–Response Assay: A Simple Regression Approach
oleh: Robin Gradin, Fleur Tourneix, Ulrika Mattson, Johan Andersson, Frédéric Amaral, Andy Forreryd, Nathalie Alépée, Henrik Johansson
Format: | Article |
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Diterbitkan: | MDPI AG 2024-08-01 |
Deskripsi
Toxicological assessments of skin sensitizers have progressed towards a higher reliance on non-animal methods. Current technological trends aim to extend the utility of non-animal methods to accurately characterize skin-sensitizing potency. The GARDskin Dose–Response assay has previously been described; it was shown that its main readout, cDV<sub>0</sub> concentration, is associated with skin-sensitizing potency. The ability to predict potency from cDV<sub>0</sub> in the form of NESILs derived from LLNAs or human NOELs was evaluated. The assessment of a dataset of 30 chemicals showed that the cDV<sub>0</sub> values still correlated strongly and significantly with both LLNA EC3 and human NOEL values (ρ = 0.645–0.787 [<i>p</i> < 1 × 10<sup>−3</sup>]). A composite potency value that combined LLNA and human potency data was defined, which aided the performance of the proposed model for the prediction of NESILs. The potency model accurately predicted sensitizing potency, with cross-validation errors of 2.75 and 3.22 fold changes compared with NESILs from LLNAs and humans, respectively. In conclusion, the results suggest that the GARDskin Dose–Response assay may be used to derive an accurate quantitative continuous potency estimate of skin sensitizers.