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Expectations for Transgenic Rodent Cancer Bioassay Models

Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, SK10 4TJ, United Kingdom, John.Ashby{at}Syngenta.com

The results of the present study have advanced dramatically the database on transgenic mouse abbreviated carcinogenicity bioassay models. As such, it will provide a secure foundationfor future evaluations of these assays and for their eventual validation as models for the prediction of possible human carcinogens. Based upon the results derived from the present study, it is suggested that 5 areas require discussion as a prelude to the further evaluation of existing models and the future evaluation of new models. First, there is the need to agree a standard list of calibration chemicals to be studied and to derive agreement on optimal bioassay group sizes, statistical methods, and exposure periods. Second, general agreement must be reached regarding the classes/types of known rodent carcinogens so that it is acceptable for the new models to fi nd negative, by implication, those rodent carcinogens considered not to pose a carcinogenic hazard to humans. Third, current understanding of mechanisms of carcinogenesis should be integrated into the evaluation of new bioassay models. Fourth, any changes made to the standard rodent carcinogenicity bioassay protocol will require compromises being made, and these should be commonly owned between interested parties in order to reduce the number of regional/agencyspecifi c carcinogenicity testing schemes. Fifth, a mechanism needs to be developed by which assays can be adopted or rejected for use in the routine bioassay of chemicals. In the absence of such initiatives the increasing number of new bioassay models will come to exist along side of the standard 2-species bioassay, and this may potentially lead to confusion regarding the true future role of these assays.

Key Words: Carcinogen • cancer bioassay • cancer model evaluation.

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