The performance of the tissue equivalent assay using the Skin(2TM) ZK1200 model in the COLIPA International Validation Study on Alternatives to the Draize Eye Irritation Test

The tissue equivalent assay (TEA) (Osborne et al., 1995) was used to evalua te 55 mixed ingredients and formulations in the COLIPA International Valida tion Study on Alternatives to the Draize Rabbit Eye Irritation Test (Branto m et at, 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 liq uid or soluble materials. A prediction model (PM) for the test was develope d using historical eye irritation data from a total of 132 materials on whi ch 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 provid ed 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 s et of coded materials and the results of both laboratories were compared to the initial PM. The TEA met the reliability criteria of the validation stu dy in reproducing the predefined PM in both laboratories, and a good relati onship between predicted and observed Draize MMAS values was obtained (r = 0.906 and r = 0.850). Good correlations were maintained when separate analy ses were made of the formulations and ingredients included in the test set. Good relationships between the in vitro endpoint and individual Draize tis sue scores (r>0.8) were also exhibited. Although insufficient data were ava ilable 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 laboratorie s suggested a sensitivity of the model to subtle differences in application techniques, and in handling and timing. Taken together, these results indi cate the utility of the TEA test for these types of substances and the need to more fully address the issue of interlaboratory reproducibility. (C) 19 99 Elsevier Science Ltd. All rights reserved.