Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
Toxicol Pathol ; 38(3): 452-71, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20305093

ABSTRACT

The rat has been the preferred rodent toxicology species since before regulatory requirements have been in place, and there exists in the pharmaceutical industry and the regulatory agencies a significant amount of historical data for the rat. The resulting experience base with the rat makes the possibility of replacing it with the mouse for regulated toxicology studies untenable for all but the most extreme circumstances. However, toxicologists are very familiar with the mouse as a model for chronic carcinogenicity studies, and there exist multiple preclinical mouse models of disease. The authors evaluated the use of the mouse for early in vivo toxicology signal generation and prioritization of small molecule lead compounds prior to nomination of a development candidate. In five-day oral gavage studies with three test agents in the mouse, the authors were able to identify the same dose-limiting toxicities as those identified in the rat, including examples of compound-mediated hemolysis as well as microscopic lesions in the alimentary canal, kidney, and pancreas. Performing early signal generation studies in the mouse allows for earlier assessment of the safety liabilities of small molecules, requires significantly less compound, and allows evaluation of more compounds earlier in the project's life cycle.


Subject(s)
Disease Models, Animal , Mice , Toxicity Tests/methods , Animals , Antineoplastic Agents/toxicity , Enzyme Inhibitors/toxicity , Male , Mice, Inbred C57BL , Rats , Rats, Sprague-Dawley
SELECTION OF CITATIONS
SEARCH DETAIL
...