Carcinogenicity studies rodent bioassay

There has been extensive debate and consideration on the relevance and value of the traditional long-term rodent bioassays. The FDA looked at rat and mouse studies for 282 human pharmaceuticals, resulting in the conclusion that sufficient evidence is now available for some alternative in vivo carcinogenicity models to support their application as complimentary studies in combination with a single two-year carcinogenicity study [emphasis added] to identify trans-species tumorigens (Contrera et al., 1997). 

Historically, the regulatory requirements for the assessment of the carcinogenic potential of pharmaceuticals recommended the conduct of long-term carcinogenicity studies in two rodent species, usually the rat and the mouse. In the 1990s, the use of transgenic mice was introduced in an attempt to improve the process of hazard identification.24 Deficiencies of the conventional bioassay are well known and include the following 25-26... 

As performance data has become available on these strains, ICH (1997) has incorporated their use into pharmaceutical testing guidelines in lieu of the second rodent species tests (that is, to replace the long-term mouse bioassay when the traditional rat study has been performed). FDA has stated that they would accept such studies when performed in a validated model. In fact, CBER has accepted such studies as a sole carcinogenicity bioassay in some cases where there was negative traditional genotoxicity data and strong evidence of a lack of a mechanistic basis for concern. 

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