Southee J A, McPherson J P, Osborne R, Carr G J, Rasmussen E
Microbiological Associates Ltd, Stirling University Innovation Park, Stirling, Scotland UK.
Toxicol In Vitro. 1999 Apr;13(2):355-73. doi: 10.1016/s0887-2333(98)00083-6.
The tissue equivalent assay (TEA) (Osborne et al., 1995) was used to evaluate 55 mixed ingredients and formulations in the COLIPA International Validation Study on Alternatives to the Draize Rabbit Eye Irritation Test (Brantom et al., 1997). The TEA can be used to test all types of materials since it uses a topical application approach and is not limited to only testing liquid or soluble materials. A prediction model (PM) for the test was developed using historical eye irritation data from a total of 132 materials on which in vivo and in vitro data were available. A regression model was derived from these data and used to relate the in vitro endpoint (t(50)) obtained in the study to a Draize MMAS (modified maximum average score). This provided a measure of the predicted in vivo eye irritation scores. In the current study, two separate laboratories used the same protocol to test the same set of coded materials and the results of both laboratories were compared to the initial PM. The TEA met the reliability criteria of the validation study in reproducing the predefined PM in both laboratories, and a good relationship between predicted and observed Draize MMAS values was obtained (r=0.906 and r=0.850). Good correlations were maintained when separate analyses were made of the formulations and ingredients included in the test set. Good relationships between the in vitro endpoint and individual Draize tissue scores (r>0.8) were also exhibited. Although insufficient data were available to make an assessment of interlaboratory variation, some difference in the reproducibility of the assay was noted between the two laboratories, particularly for the highly irritating materials. However, the consistency of data was encouraging and the discrepancies seen between the laboratories suggested a sensitivity of the model to subtle differences in application techniques, and in handling and timing. Taken together, these results indicate the utility of the TEA test for these types of substances and the need to more fully address the issue of interlaboratory reproducibility.
在COLIPA国际兔眼刺激性试验替代方法验证研究（Brantom等人，1997年）中，采用组织等效性试验（TEA）（Osborne等人，1995年）对55种混合成分和配方进行评估。由于TEA采用局部应用方法，不限于仅测试液体或可溶性材料，因此可用于测试所有类型的材料。利用来自总共132种材料的历史眼刺激性数据开发了该试验的预测模型（PM），这些材料既有体内数据也有体外数据。从这些数据中得出一个回归模型，用于将研究中获得的体外终点（t(50)）与德雷兹改良最大平均评分（Draize MMAS）相关联。这提供了预测体内眼刺激性评分的一种方法。在当前研究中，两个独立的实验室使用相同的方案测试同一组编码材料，并将两个实验室的结果与初始PM进行比较。TEA在两个实验室中重现预定义PM方面符合验证研究的可靠性标准，并且预测的和观察到的德雷兹MMAS值之间具有良好的关系（r = 0.906和r = 0.850）。对测试集中包含的配方和成分进行单独分析时，保持了良好的相关性。体外终点与各个德雷兹组织评分之间也呈现出良好的关系（r>0.8）。尽管没有足够的数据来评估实验室间的差异，但注意到两个实验室之间在该试验的可重复性方面存在一些差异，特别是对于高刺激性材料。然而，数据的一致性令人鼓舞，实验室之间的差异表明该模型对应用技术、处理和时间安排中的细微差异敏感。综上所述，这些结果表明TEA试验对于这类物质的实用性以及更全面解决实验室间可重复性问题的必要性。
