The classical chronic carcinogenicity bioassay has served researchers well over the last few decades. Recently, however, several factors have prompted a reevaluation of this approach, including budget pressures, a growing list of agents for study, and a better understanding of carcinogenesis. Herein some emerging strategies for obtaining similar or better information are considered. Rather than basing hazard identification and risk estimation on chronic bioassays of two sexes in two species, the possibility of a “reduced protocol” using a subset of the four assays is considered. The possibility of supplementing reduced protocol results from maximum tolerated dose information is raised. The trend to biologically based dose response models is considered, especially with reference to statistical issues associated with the “two-stage birth-death” model and physiologically-based pharmacokinetic models.
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