In vitro toxicology: a commercial proposition?
1. The commercial value of any test system must be equated with its scientific value. In vitro toxicity tests only have scientific value when they are accurate models of toxicity in vivo. 2. Toxicity is a complex event so that the simple tests of cell viability are unlikely to be useful models as these tests often use cell lines which are functionally remote from cells in tissues of the whole animal. 3. Primary cultures retain their differentiated function for hours (hepatocytes) or days (nerve cells) and may acquire differentiated functions in vitro (embryo cells) and are the models of choice for predicting toxic hazard. 4. When the in vitro test is a satisfactory predictive model of toxicity there are sound commercial reasons for its use. It saves time and effort and can be used at an early stage in compound development to sort out the toxic from the non-toxic candidate compounds. Large numbers of structurally similar compounds can be tested (QSAR studies) and a greater understanding of the mechanism of toxic action can often be achieved than in vivo because of the numbers of animals required and the interplay of different organ systems in the toxic events that make interpretation difficult. Thus the in vitro test can not only save animals but can also save compounds.
Imperial Chemical Industries PLC, Pharmaceutical Division, Macclesfield, Cheshire, UK.
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D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology