Botham Philip A
Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield SK10 4TJ, UK.
Toxicol Lett. 2004 Apr 1;149(1-3):387-90. doi: 10.1016/j.toxlet.2003.12.048.
Several alternative in vitro methods for identifying skin irritants have been developed in the last 10 years, the most promising of which use either reconstituted human skin models or animal (e.g. pig or mouse) skin organ cultures. In 1998, the European Centre for the Validation of Alternative Methods (ECVAM) commissioned a pre-validation study of five methods. Two reconstituted human skin methods (Epiderm and EPISKIN) and one animal skin model (the mouse skin integrity function test, SIFT) performed well in Phases I and II of the study (intralaboratory reproducibility and protocol transfer) and proceeded to Phase III which assessed reproducibility and predictive ability in three independent laboratories using a set of 20 coded test chemicals (10 irritants and 10 non irritants). Intralaboratory reproducibility was again acceptable for all three methods but inter-laboratory reproducibility was acceptable only for EPISKIN. The predictive ability of all three methods was also inadequate. Following refinements to the protocols of Epiderm and EPISKIN and changes to the statistical analysis of SIFT, the predictive ability was improved. In 2003, ECVAM concluded that they could proceed to a full validation study. This will be conducted in two phases and is scheduled for completion early in 2005.
在过去十年中，已开发出几种用于识别皮肤刺激物的体外替代方法，其中最有前景的方法是使用重组人皮模型或动物（如猪或小鼠）皮肤器官培养物。1998年，欧洲替代方法验证中心（ECVAM）委托对五种方法进行预验证研究。两种重组人皮方法（Epiderm和EPISKIN）和一种动物皮肤模型（小鼠皮肤完整性功能测试，SIFT）在研究的第一阶段和第二阶段（实验室内再现性和方案转移）表现良好，并进入第三阶段，该阶段使用一组20种编码测试化学品（10种刺激物和10种非刺激物）在三个独立实验室评估再现性和预测能力。所有三种方法的实验室内再现性再次可以接受，但只有EPISKIN的实验室间再现性可以接受。所有三种方法的预测能力也不足。对Epiderm和EPISKIN的方案进行改进并对SIFT的统计分析进行更改后，预测能力得到了提高。2003年，ECVAM得出结论，它们可以进行全面验证研究。这将分两个阶段进行，计划于2005年初完成。
