Bioassay design and MTD setting: old methods and new approaches.

The proper design of carcinogenicity bioassays is critical to the interpretation and use of the data that emerge upon its completion. This paper explores some of the scientific underpinnings that need to be considered when designing bioassays. It also discusses new approaches that can be used to improve dose setting and interpretation of bioassay results. Critical information that determines the shape of the dose-response curve include the molecular dose of the agent that binds to DNA, cell proliferation, and cell death. Such data can be used to replace default assumptions and improve the extrapolation of risk from animal studies to humans.