Overview of the Final MEIC Results: I. The In Vitro--In Vitro Evaluation.

In the MEIC study, the first 30 reference chemicals were tested in 82 in vitro toxicity assays while the last 20 chemicals were tested in 67 assays. To increase understanding of the performance of in vitro toxicity tests, these two subsets of results were compared by principal components analyses (PCA) combined with a "random probe" analysis of five key methodological factors, that is, the results from all pairs of methods which were similar in all other respects than the analysed factor were systematically compared by linear regression. This paper is an overview of these published comparisons, and also includes a new "random probe" analysis of another segment of the same MEIC results, namely tests of all 50 reference chemicals by 61 of the methods. A PCA indicated high general similarity (around 80%) of all the results from the 61 methods. According to the new "random probe" analysis, this similarity must depend on the high correlation of results from assays with different cell types (mean R(2) 0.81) and/or different viability endpoints (mean R(2) 0.85). Main factors contributing to the 20% dissimilarity of results were different exposure times and the use of phylogenetically distant test objects in the non-analogous ecotoxicological assays. As expected, the new analysis of the 61 methods gave roughly similar results as the previous "random probe" analyses of the other two segments of the data. Findings support the basal cytotoxicity concept and will improve future in vitro toxicity testing. This testing will probably need assays with varied exposure times. As judged from the similarity of the results, simple assays with cell lines may replace complicated primary culture systems for many testing purposes (e.g. screening).