利用人皮肤模型评价杀菌类农药的腐蚀/刺激性

Using Human Skin Model to Evaluate Skin Corrosion/Irritation of Fungicide

建立人皮肤模型检测杀菌类农药的腐蚀/刺激性,探讨体外皮肤模型替代农药的动物皮肤安全性评价实验的可行性和影响因素。使用人皮肤成纤维细胞与鼠尾胶原混合培养模拟真皮层,在真皮层上接种人角化细胞,经气液培养形成表皮层。通过细胞活性和细胞因子测定鉴别化合物的腐蚀/刺激性,并比较体外皮肤模型和动物测试结果的一致性。结果表明,皮肤模型对十种农药的腐蚀性测试中,与动物安全评价测试结果完全一致。在刺激性试验中,细胞因子白介素-1a(IL-1a)作为检测终点提高了体外皮肤模型的灵敏性和准确性,人皮肤模型和动物测试结果的一致性达到80%。研究表明,构建的人皮肤模型在对杀菌类农药腐蚀/刺激性测试中初步表现出较好的性能,作为动物替代方法进行农药品安全性评价具有良好的应用前景。

To explore the feasibility and the influencing factors of human skin model in evaluating the safety of pesticide, as an alternative approach to the animal experiment, human skin model was developed and the skin corrosion and irritation of fungicides were measured. Human fibroblasts mixing with rat rail collagen were cultured to simulate the dermal tissue. Then human keratinocytes were cultivated upon the dermal tissue under air liquid interface forming the stratum corneum. The corrosion and irritation were evaluated according to cellular activity and IL-1a releasing level in human skin model, which were compared with the results of animal experiments. The corrosion results obtained from human skin model for ten fungicides totally agreed with that got from the animal test.In irritation test, IL-1a analysis contributed to improve the sensitivity and accuracy of the human skin model, and the consistency between the animal results and skin model results reached 80%. The present study preliminarilysuggested that human skin model exhibited good performance in the identification of fungicides corrosion and irritation and showed a good application prospect as an alternative approach in the safety evaluation of pesticide.