采用in silico和in chemico技术评价对氨基酚的皮肤致敏性

目的：采用定量构效关系（QSAR）方法和直接肽结合试验（DPRA）对对氨基酚的皮肤致敏性进行评价。方法：计算机模拟评价（in silico）采用DEREK软件，对化合物的皮肤致敏性进行预测；体外化学分析法（in chemico）采用DPRA试验，用高效液相色谱仪对对氨基酚的多肽消除率进行检测，对其皮肤致敏性进行分级。同时比较2种方法结果一致性。结果：QSAR预测EC₃值为0.37%，对应的致敏性分级为强致敏物；DPRA试验的系统适应性符合要求，样品对半胱氨酸多肽的消除率分别为100%，对赖氨酸多肽的消除率分别为43.10%，计算得对氨基酚的多肽消除率为71.55%，对应的致敏性分级为强致敏物。结论：对氨基酚为强致敏性物质。

Objective: To evaluate the skin sensitizing potential of p-aminophenol by direct peptide reactivity assay (QSAR)and quantitative structure-activity relationship (DPRA)method. Methods: DEREK software was used as an in silico method to predict the skin sensitizing potential of the compound. DPRA was used as an in chemico method. The depletion rates of peptides after exposure to p-aminophenol were measured by high performance liquid chromatography (HPLC)to obtain the sensitization grades of the compound. Furthermore, the consistency of two method results was compared. Results: The predicted EC₃ value of QSAR was 0.37%, which indicated p-aminophenol was a strong sensitizer. The depletion rate of cysteine and lysine peptides was 100% and 43.10%, respectively. The calculated depletion rate of peptides after exposure to p-aminophenol were 71.55%, which indicated p-aminophenol was a strong sensitizer. Conclusion: p-Aminophenol is a strong sensitizer.

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