The multicentre evaluation of in vitro cytotoxicity (MEIC) study is a programme designed to evaluate the relevance of in vitro toxicity tests for predicting human toxicity, and is organised by the Scandinavian Society for Cell Toxicology. The project started in 1989 and is scheduled to be finished by June 1996. MEIC is a voluntary effort by international laboratories to test the same 50 reference chemicals in their own in vitro toxicity systems. At present, 31 laboratories have submitted results for the first 30 reference chemicals from a total of 68 in vitro cytotoxicity tests. In the definitive evaluation of the MEIC programme, these in vitro results will be compared with human lethal blood concentrations and other relevant acute systemic toxicity data, and the results will be published as a series of articles. This paper, which is the first article in this series, describes and analyses the methodologies used in the 68 tests. The origins and purities of the test chemicals, the biological systems and the toxicity endpoints are also discussed. Since MEIC is not centrally directed, the selection of tests was entirely dependent on the preferences of the individual laboratories. Thus, the collection of tests is not representative of the full range of existing in vitro toxicity tests. In our study, basal cytotoxicity tests and ecotoxicological tests are prevalent, while tests for toxicity to primary cultures of differentiated cells, measured by organotypic toxicity endpoints, are clearly under-represented.
In order to evaluate the relevance of in vitro test systems for acute toxicity assessment, quantitative comparisons of in vitro and in vivo potency data have to be performed. The potency of chemicals to cells in vitro is usually characterised by nominal effective concentrations (e.g. EC50 values). Often, the only available in vivo data are acute lethal body doses (e.g. LD50 values). To enable a reasonable quantitative in vitro–in vivo comparison to be made, a formula has been developed to permit the conversion of EC50 values into “effective model body doses, ED50 values”. This formula takes into account the lipophilicity of the compounds and the very different relationships between the volumes of the lipid and water compartments in vitro and in vivo. The suitability of this approach is evaluated with results obtained for the first 30 MEIC chemicals.
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