Publication Details

Category Text Publication
Reference Category Journals
DOI 10.1177/026119299802601s02
Title (Primary) MEIC evaluation of acute systemic toxicity - Part III. In vitro results from 16 additional methods used to test the first 30 reference chemicals and a comparative cytotoxicity analysis
Author Clemedson, C.; Barile, F.A.; Ekwall, B.; Gómez-Lechón, M.J.; Hall, T.; Imai, K.; Kahru, A.; Logemann, P.; Monaco, F.; Ohno, T.; Segner, H.; Sjöström, M.; Valentino, M.; Walum, E.; Wang, X.H.; Ekwall, B.
Journal ATLA-Alternatives to Laboratory Animals
Year 1998
Department OEC; COE
Volume 26
Page From 93
Page To 129
Language englisch
Keywords alternatives; basal cytotoxicity; biostatistics; comparative cell toxicology; cultured cells; cytotoxicity endpoints; differential cytotoxicity; evaluation; in vitro cytotoxicity; MEIC; multivariate analysis; organ-specific toxicity; toxicity testing; validation
Abstract Results from tests on the first 30 MEIC reference chemicals in 16 different systems are presented as a prerequisite to the subsequent in vitro/in vivo comparisons of acute toxicity data, i.e. the final MEIC evaluation of all test results of the study. The study is a supplement to the previously published results from 68 methods (including methods 45B and 46B [old numbers]) used to test the same set of chemicals. The strategies and methods of the preceding paper were employed to enable a comparative cytotoxicity analysis of the results from these 68 methods and from the 16 new methods to be made. Principal components analysis (PCA) of 82 assays demonstrated a dominating first component which described as much as 83% of the variance in the toxicity data. This remarkable similarity of all toxicity data was the main finding of the present study, and confirmed the results of the previous study with a less-extensive database. Also, the influence on the general variability of results of several key methodological factors was evaluated by analysis of selected sets of data, including linear regression of the results of pairs of methods, which were similar in all respects except for the factor under analysis. This analysis of the same 82 assays as before also confirmed previous results from the 68 assay database: a) the toxicities of a third of the chemicals increased considerably with exposure time; b) in general, cytotoxicity for human cells was well predicted by cytotoxicity tests with animal cells; c) this prediction was poor for two chemicals, i.e. digoxin and malathion; d) prediction of human cytotoxicity by ecotoxicological tests was only fairly good; e) 25 comparisons of similar assays employing different cell lines showed strikingly similar toxicities (mean R2 = 0.86); f) 22 comparisons of similar pairs of assays employing different primary cultures and cell lines also revealed similar toxicities (mean R2 = 0.79); and g) 15 comparisons of similar assays with different growth/viability endpoint measurements demonstrated strikingly similar toxicities (mean R2 = 0.89). Results b, e, f and g must be the main causes of the general similarity of results, while results a, c and d, together with other factors, could explain the 20% dissimilarity. These findings support the basal cytotoxicity concept and may assist in guiding and refining in vitro toxicity testing in the future.
Persistent UFZ Identifier
Clemedson, C., Barile, F.A., Ekwall, B., Gómez-Lechón, M.J., Hall, T., Imai, K., Kahru, A., Logemann, P., Monaco, F., Ohno, T., Segner, H., Sjöström, M., Valentino, M., Walum, E., Wang, X.H., Ekwall, B. (1998):
MEIC evaluation of acute systemic toxicity - Part III. In vitro results from 16 additional methods used to test the first 30 reference chemicals and a comparative cytotoxicity analysis
ATLA-Altern. Lab. Anim. 26 , 93 - 129