MEIC EVALUATION OF ACUTE SYSTEMIC TOXICITY. PART VI: THE PREDICTION OF HUMAN TOXICITY BY RODENT LD50 VALUES AND RESULTS FROM 61 IN VITRO METHODS

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Authors
  1. Ekwall, B.
  2. Bariel, F.A.
  3. Castano, A.
  4. Clemedson, C.
  5. Sawyer, T.W.
  6. and others
Corporate Authors
Defence Research Establishment Suffield, Ralston ALTA (CAN)
Abstract
The Multicenter Evaluation of In Vitro Cytotoxicity (MEIC) programme was set up to evaluate the relevance for human acute toxicity of in vitro cytotoxicity tests. At the end of the project in 1996, 29 laboratories had tested all 50 reference chemicals in 61 cytotoxicity assays. Five previous articles have presented the in vitro data and the human database to be used in the evaluation. This article presents three important parts of the final evaluation: (a) a comparison of rat and mouse oral LD50 with human acute lethal doses for all 50 chemicals; (b) a display of the correlations between IC50 (concentration causing 50% inhibition) values from all 61 assays and three independent sets of human acute lethal blood concentrations, i.e. clinical lethal concentrations, forensic lethal concentrations, and peak concentrations; and (c) a series of comparisons between average IC50 values from ten human cell line 24-hour assays and human lethal blood concentrations. In the latter comparisons, results from correlations ere linked with known human toxicity data for the chemicals, to provide an understanding of correlative results. This correlative/mechannistic appraoch had the double purpose of assessing the relevance of the in vitro cytotoxicities, and of testing a series of hypotheses connected with the basal cytotoxicity concept. TRUNCATED
Keywords
Basal cytotoxicity;Comparative ceel toxicology;Differential cytotoxicity;In vitro toxicology;Multivariate analysis;Toxicity testing
Report Number
DRES-OL-97-014 — Reprint
Date of publication
01 Sep 1998
Number of Pages
45
Reprinted from
ATLA, vol 26, 1998, p 617-658
DSTKIM No
98-02788
CANDIS No
509588
Format(s):
Hardcopy;Document Image stored on Optical Disk

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