Protein precipitation In Vitro as a measure of chemical-induced cytotoxicity: an EDIT sub-programme.

As a priority area of the Evaluation-Guided Development of In Vitro Toxicity and Toxicokinetic Tests (EDIT) programme, an in vitro protein precipitation (PP) assay was used on the 50 reference chemicals of the Multicentre Evaluation of In Vitro Cytotoxicity (MEIC) project, to confirm and extend the MEIC results. Dose-response curves were generated for only 30 of the chemicals, and the concentrations causing 10% (EC10) and 50% (EC50) protein precipitation versus the positive control were chosen as endpoints. The number of chemicals with a positive response increased to 46 when a new endpoint, the minimum effect concentration (MEC) that induces protein precipitation with respect to the negative control, was used.

In vitro long-term cytotoxicity testing of 27 MEIC chemicals on Hep G2 cells and comparison with acute human toxicity data.

Within the framework of the EDIT (Evaluation guided Development of In vitro Toxicity and toxicokinetic tests) programme, the long-term cytotoxicity of 27 chemicals was investigated on Hep G2 cells. The first step in the experiments was to determine the PI50(24h) of the chemicals. This is the concentration of compound needed to reduce the total protein content by 50% after 24 h of treatment.

Overview of the Final MEIC Results: II. The In Vitro--In Vivo Evaluation, Including the Selection of a Practical Battery of Cell Tests for Prediction of Acute Lethal Blood Concentrations in Humans.

In MEIC, all 50 reference chemicals were tested in 61 in vitro assays. To provide a background to the in vitro/in vivo evaluation, mouse LD(50) values were compared with human lethal doses, resulting in a good correlation (R(2) 0.65).

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.