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

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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 1Multicenter 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.

TABLE 1

The First 50 Reference Chemicals of the MEIC Project

1. Acetaminophen

26. Arsenic trioxide

2. Aspirin

27. Cupric sulfate

3. Ferrous sulfate

28. Mercuric chloride

4. Diazepam

29. Thioridazine HCl

5. Amitriptyline

30. Thallium sulfate

6. Digoxin

31. Warfarin

7. Ethylene glycol

32. Lindane

8. Methyl alcohol

33. Chloroform

9. Ethyl alcohol

34. Carbon tetrachloride

10. Isopropyl alcohol

35. Isoniazid

11. 1,1,1-Trichloroethane

36. Dichloromethane

12. Phenol

37. Barium nitrate

13. Sodium chloride

38. Hexachlorophene

14. Sodium fluoride

39. Pentachlorophenol

15. Malathion

40. Verapamil HCl

16. 2,4-Dichlorophenoxyacetic acid

41. Chloroquine pholphate

17. Xylene

42. Orphenadrine HCl

18. Nicotine

43. Quinidine sulfate

19. Potassium cyanide

44. Diphenylhydantoin

20. Lithium sulfate

45. Chloramphenicol

21. Theophylline

46. Sodium oxalate

22. Dextropropoxyphene HCl

47. Amphetamine sulfate

23. Propranolol HCl

48. Caffeine

24. Phenobarbital

49. Atropine sulfate

25. Paraquat

50. Potassium chloride

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Abbreviations

LD50 :

acute, median lethal dosage

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Authors and Affiliations

  1. Swedish Poison Information Center, Karolinska Hospital, Stockholm, Sweden

    Inger Bondesson

  2. Department of Toxicology, University of Uppsala, Uppsala, Sweden

    Björn Ekwall

  3. Research Group of Chemometrics Department of Chemistry, University of Umeå, Umeå, Sweden

    Sven Hellberg

  4. Department of Genetic and Cellular Toxicology Wallenberg Laboratory, University of Stockholm, Stockholm, Sweden

    Lennart Romert

  5. Department of Medical Radiobiology, Karolinska Institute, Stockholm, Sweden

    Kjell Stenberg

  6. Department of Neurochemistry and Neurotoxicology, University of Stockholm, Stockholm, Sweden

    Erik Walum

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  1. Inger Bondesson
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Bondesson, I., Ekwall, B., Hellberg, S. et al. MEIC—A new international multicenter project to evaluate the relevance to human toxicity of in vitro cytotoxicity tests. Cell Biol Toxicol 5, 331–347 (1989). https://doi.org/10.1007/BF01795360

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