Current alternatives to animal testing methods for skin irritation evaluation such as reconstructed human epidermis models are not fully representing physiological response caused by skin irritants. Skin irritation is physiologically induced by the dilation and increased permeability of endothelial cells. Thus, our objectives were to mimic physiological skin irritation using a skin-on-a-chip model and compare predictive capacities with a reconstructed human epidermis model to evaluate its effectiveness. To achieve our goals, the skin-on-a-chip model, consisting of three layers representing the epidermal, dermal and endothelial components, was adapted. Cell viability was measured using the OECD TG 439 protocol for test substance evaluation. The tight junctions of endothelial cells were also observed and measured to assess physiological responses to test substances. These parameters were used to physiologically evaluate cell-to-cell interactions induced by test substances and quantify model accuracy, sensitivity, and specificity. Based on in vivo data, the classification accuracy of twenty test substances using a dual-parameter chip model was 80%, which is higher than other methods. Besides, the chip model was more suitable for simulating human skin irritation. Therefore, it is important to note that the dual-parameter chip model possesses an enhanced predictive capacity and could serve as an alternative to animal testing for skin irritation.

用于皮肤刺激性评估的动物测试方法的当前替代方法（例如重建的人表皮模型）不能完全代表由皮肤刺激性物质引起的生理反应。内皮细胞的扩张和通透性增加是生理上引起的皮肤刺激。因此，我们的目标是使用芯片上皮肤模型模拟生理性皮肤刺激，并将预测能力与重建的人表皮模型进行比较以评估其有效性。为了实现我们的目标，对芯片上皮肤模型进行了修改，该模型由代表表皮，真皮和内皮成分的三层组成。使用OECD TG 439协议测量细胞活力，以评估测试物质。还观察和测量了内皮细胞的紧密连接，以评估对测试物质的生理反应。这些参数用于生理评估受试物质诱导的细胞间相互作用，并量化模型的准确性，敏感性和特异性。基于在体内数据中，使用双参数芯片模型对二十种测试物质的分类准确性为80％，高于其他方法。此外，芯片模型更适合于模拟人的皮肤刺激。因此，重要的是要注意，双参数芯片模型具有增强的预测能力，并且可以作为动物刺激皮肤的替代方法。