In Vitro Toxicity Testing: Purpose, Validation and Strategy

The fullest potential for in vitro evaluation of toxicity will be realised in the context of the process of assessing the risk of human toxicity. This article is an attempt to clarify what contributions can be made by in vitro tests and what types of in vitro test can best be used. In vitro tests are clarified according to the type of biological endpoint evaluated, first into tests for general (‘basal’) cytotoxicity and, secondly, into tests for differentiated cell function. The role of each type of test is analysed and it is suggested that tests for general cytotoxicity, as opposed to differentiated function, are difficult to interpret in terms of in vivo toxicity. A general approach to evaluating in vitro tests is described, and a strategy for using these tests is proposed.

[1]  G. Krishna,et al.  Structural requirements for inducing cardiotoxicity by anthracycline antibiotics: studies with neonatal rat cardiac myocytes in culture. , 1986, Toxicology and applied pharmacology.

[2]  M. Balls,et al.  The FRAME multicentre project on in vitro cytotoxicology. , 1986, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[3]  O. Flint,et al.  Structure-Teratogenicity Relationships Among Antifungal Triazoles , 1990 .

[4]  L P Brown,et al.  Teratogenicity of phenylhydantoins in an in vitro system: molecular orbital-generated quantitative structure-toxicity relationships. , 1989, Xenobiotica; the fate of foreign compounds in biological systems.

[5]  S Kalweit,et al.  Validation project of alternatives for the Draize eye test. , 1987, Molecular toxicology.

[6]  T. Mosmann Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. , 1983, Journal of immunological methods.

[7]  O. Flint,et al.  An in vitro test for teratogens using cultures of rat embryo cells , 1987 .

[8]  O. Flint,et al.  An in vitro assay for teratogens with cultures of rat embryo midbrain and limb bud cells. , 1984, Toxicology and applied pharmacology.

[9]  A. Guillouzo,et al.  Different cytotoxicity and metabolism of doxorubicin, daunorubicin, epirubicin, esorubicin and idarubicin in cultured human and rat hepatocytes. , 1988, Biochemical pharmacology.

[10]  O. Flint,et al.  In vitro toxicology: a commercial proposition? , 1988, Xenobiotica; the fate of foreign compounds in biological systems.

[11]  S. Snyder,et al.  Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6 -tetrahydropyridine: uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity. , 1985, Proceedings of the National Academy of Sciences of the United States of America.