Gradin Robin, Tourneix Fleur, Mattson Ulrika, Andersson Johan, Amaral Frédéric, Forreryd Andy, Alépée Nathalie, Johansson Henrik
Senzagen AB, 22381 Lund, Sweden.
L'Oréal, Research & Innovation, 93600 Aulnay-sous-Bois, France.
Toxics. 2024 Aug 24;12(9):626. doi: 10.3390/toxics12090626.
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 concentration, is associated with skin-sensitizing potency. The ability to predict potency from cDV 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 values still correlated strongly and significantly with both LLNA EC3 and human NOEL values (ρ = 0.645-0.787 [ < 1 × 10]). 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.
皮肤致敏剂的毒理学评估已越来越依赖非动物方法。当前的技术趋势旨在扩大非动物方法的应用范围，以准确表征皮肤致敏效力。之前已描述过GARDskin剂量反应试验；结果表明，其主要读数cDV浓度与皮肤致敏效力相关。评估了从LLNAs或人类NOELs得出的以NESILs形式通过cDV预测效力的能力。对30种化学物质的数据集评估表明，cDV值与LLNA EC3和人类NOEL值仍具有强且显著的相关性（ρ = 0.645 - 0.787 [ < 1 × 10]）。定义了一个结合LLNA和人类效力数据的复合效力值，这有助于所提出的NESILs预测模型的性能表现。该效力模型准确预测了致敏效力，与来自LLNAs和人类的NESILs相比，交叉验证误差分别为2.75倍和3.22倍变化。总之，结果表明GARDskin剂量反应试验可用于得出皮肤致敏剂准确的定量连续效力估计值。
