Selection and Validation of Toxicogenomics Assays as Alternatives to Animal Tests

Toxicogenomics-based methods are providing promising perspectives in the reduction and replacement of toxicity testing of chemicals and pharmaceuticals using experimental animals. Transcriptomics using DNA arrays and related methods can be used to select signature profiles of genes that can predict the response of a cell or organism. These genes sets can also be used to identify the pathways involved in toxic effects of chemicals and, based on that knowledge, design relatively straightforward molecular screening tools measuring modulation of these key toxicity pathways. Many of these methods bear great promise but have not matured sufficiently to reach regulatory application and, therefore, their impact on replacement of experimental animals is still limited to scientific applications. To be able to profit to the full extent from the possibilities of these modern toxicogenomics and related molecular screening tools, essential hurdles towards regulatory acceptance need to be passed. One of the main obstacles towards regulatory acceptance is the need to validate these tests in a manner that is acceptable to regulators. Although the principles of validation are straightforward, in practice this aspect of test development is very often neglected and the efforts to reach a validated test grossly underestimated. In this chapter, the possibilities, requirements, and feasibility of validating toxicogenomics-based tests are discussed, to provide insight and guidance in this process.