MEIC—A new international multicenter project to evaluate the relevance to human toxicity of in vitro cytotoxicity tests

Abstract

A new international project to evaluate the relevance for human systemic and local toxicity of in vitro tests of general toxicity of chemicals has been organized by the Scandinavian Society of Cell Toxicology under the title Multicenter Evaluation of In Vitro Cytotoxicity (MEIC). The basic assumptions underlying the project, as well as the practical goals and the design of the program are outlined. The list of the first 50 reference chemicals is presented. The chemicals are an otherwise unbiased selection of compounds with known human acutely lethal dosage and blood concentrations, including LD50-values in the rat or mouse. Most agents also have other data on human toxicity and toxicokinetics, including more extensive animal toxicity data. International laboratories already using or developing in vitro tests of various partial aspects of general toxicity are invited to test the substances, the results of which will be evaluated by us. The predictivity of the in vitro results for both partial and gross human toxicity data will be determined with combined use of univariate regression analysis and soft multivariate modeling. The predictivity of the in vitro results will be compared with the predictivity of conventional animal tests for the same chemicals. Finally, batteries of tests with optimal prediction power for various types of human toxicity will be selected. The need for and possible uses of such batteries are discussed.

Chemically induced strong cellular hypertrophy often reduces the accuracy of cytotoxicity measurements obtained using the ATP assay

“…Because the ATP assay is often used to evaluate cytotoxicity in an in vitro mammalian cell genotoxicity test, 12 of the compounds used in this study were those reported by Matsushima et al (1999) to possess various genotoxic properties. In addition, 7 compounds were selected from a report that established drug cytotoxicity (Evans et al, 2001), and 5 compounds were selected from a report based on a multicenter evaluation of in vitro cytotoxicity (MEIC) (Bondesson et al, 1989). Because sensitivity to cytotoxicity may be changed by cell density, we confirmed that the doubling time of the control cells corresponds to the logarithmic growth phase of CHL cells during drug treatment in this experiment.…”

High-content analysis for drug delivery and nanoparticle applications

“…A 7-year, international, multicenter study (MEIC) involving 29 laboratories and 61 different cytotoxicity assays evaluated the relevance of in vitro cytotoxicity testing in numerous cell types in relation to in vivo human toxicity [18]. Fifty chemicals were studied, including poisons, prescription drugs, substances of abuse, and common household chemicals.…”

Scandinavian Society for Cell Toxicology – Thirty Years of Scientific Pioneering

“…The second mission was concretized in the form of the Multicentre Evaluation of In vitro Cytotoxicity (MEIC) programme, directed at an evaluation of the predictive value for human toxicity of in vitro cytotoxicity tests. The study was launched in 1989 [6] and completed in 1999 [7].…”