MEIC EVALUATION OF ACUTE SYSTEMIC TOXICITY .2. IN-VITRO RESULTS FROM 68 TOXICITY ASSAYS USED TO TEST THE FIRST 30 REFERENCE CHEMICALS AND ACOMPARATIVE CYTOTOXICITY ANALYSIS

Results from tests of the first 30 MEIC reference chemicals in 68 diff erent toxicity assays are presented as a prerequisite to subsequent in vitro/in vivo comparisons of acute toxicity data. A comparative cytot oxicity study was also carried out. Firstly, the variability of all of the results was analysed by using principal components analysis (PCA) , analyses of variance (ANOVAs) and pairwise comparisons of means acco rding to Tukey's method. The first PCA component described 80% of the variance of all of the cytotoxicity data. Tukey's ANOVA indicated a si milar sensitivity for the assays, of approximately 80%. Secondly, the influence of five major methodological components on the general varia bility of the results was evaluated by linear regression and ANOVA lin ear contrast analyses. The findings were that: a) the toxicity of many chemicals increased with exposure time; b) in general, human cytotoxi city was predicted well by animal cytotoxicity tests; c) this predicti on was poor for two chemicals; d) the prediction of human cytotoxicity by the ecotoxicological tests was only fairly good; e) one organotypi c endpoint used, i.e. contractility of muscle cells, gave different re sults to those obtained according to viability/growth toxicity criteri a; f) twelve comparisons of similar test systems involving different c ell types (including highly differentiated cells) showed similar toxic ities regardless of cell type; and g) nine out of ten comparisons of t est systems with identical cell types and exposure times revealed simi lar toxicities, regardless of the viability or growth endpoint measure ment used. Factors b, f and g must be the main causes of the remarkabl e similarity between the total results, while factors a, c, d and e, t ogether with other minor factors that were not analysed, contributed t o the 20% dissimilarity. The findings strongly support the basal cytot oxicity concept, and will facilitate future in vitro toxicity testing.