Whole animal screens

Campbell, D. and Richter, W. (1967). Whole animal screening studies. Act. Pharmacol. 25 345-363. 

Figure 4. Illustration of the significance of a structure-activity relationship using in vitro metabolism, Ames assay, partition coefficients, or whole animal screens to develop the structure-activity relationship...

Less complex test systems, including nonmammalian and in vitro cultures, are recommended only for pre-screening or secondary studies to elucidate mechanisms. A useful statement for use with lACUC committees comes from this section, as follows In short, there are no alternative test systems to whole animals currently available for reproduction toxicity testing with the aims set out in the introduction. ... 

A number of in vitro developmental systems have been used to investigate the morphological and biochemical basis of normal and abnormal development. Examples include cell, organ and whole embryo culture. Although it is unlikely that in vitro systems will ever be able to replace whole animal systems for risk assessment, in vitro tests are very useful when used in addition to in vivo studies (Stahlmann et al., 1993). In particular, they are useful to study the mechanisms of normal and abnormal development, to determine dose-response, to identify organ toxicity and perhaps to screen or prioritize chemicals for further in vivo studies. However, most in vitro tests focus on a narrow range of developmental events thus, some researchers feel that in vitro studies should be based on previously characterized results from in vivo studies (Schwetz, 1993). 

Hie greatest difficulty with test systems today is that the tests that are most economical and sensitive use cell cultures, or, if they use whole animals, animals that are phylogenetically distant from man. In contrast, tests that use the mouse in ways that are directly comparable with the presumed human experience are too expensive to use for more than a small number of chemicals. Thus, in the tiered screening system detailed in Chapter 9, the Committee recommends that mouse tests be used only when the simpler tests have not provided enough information for a decision or when the chemical in question is so important or widespread in its use that further information is deemed crucial. 

Twenty years ago, the initial screening of new compounds for pharmacologic activity was conducted using whole animals or tissues and organs isolated from animals. Today most of the initial screening for new drugs is done in vitro using the techniques of... 

Often it is possible to replace a toxicity test with an alternative methodology, especially when cellular or mechanistic studies are undertaken. Tissue in laboratory culture, microorganisms, or lower invertebrates can also be used in place of whole animal studies. In the case of screening tests, there now exists a broad variety of quantitative structure-activity models that can predict and... 

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