Principles and practices of integrating genotoxicity evaluation into routine toxicology studies: A pharmaceutical industry perspective
✍ Scribed by G. Krishna; G. Urda; J. Theiss
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 147 KB
- Volume
- 32
- Category
- Article
- ISSN
- 0893-6692
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✦ Synopsis
In this article, an integrated in vivo genotoxicity test-multiple tolerable doses aiding in achieving steady ing philosophy and a practical approach, as ap-state plasma drug levels, which is more relevant for plied to pharmaceuticals, are described. Recently, risk assessment compared to high acute doses; and there has been an effort to integrate the rodent (pri-4) it helps minimize the amount of drug, number of marily rat) micronucleus assay with routine 2-4-animals used, and other resources. This integration week toxicokinetic studies. This approach has sev-approach can be extended to other toxicology studeral advantages: 1) it utilizes the general principles ies and other relevant genotoxicity endpoints may of toxicology that govern the overall toxicity profile be assessed. Based on the experience in our laboraof a test substance; 2) factors such as the dose tory, integrating micronucleus assessment in routine and/or route of drug administration, drug metabo-toxicology testing is promising and should be utilism, principles of toxicokinetics, and saturation of lized when practical. Environ. Mol. Mutagen. defense mechanisms are considered in evaluating 32: 115-120, 1998 ᭧ 1998 Wiley-Liss, Inc. genotoxicity; 3) it uses the concept of administering