Scientific Publications by FDA Staff

Drug Info J 1989 Apr;23(2):303-7

Estimation of Cancer Risk

Gaylor DW

In rare instances human dose-response data exist relating cancer risk to dose. Generally, cancer risk estimates must be based on the results of animal bioassays. Animals are generally dosed at levels exceeding human exposure levels to elicit potential toxic effects in relatively small numbers of animals. The problem of high- to low-dose extrapolation is discussed. In addition, extrapolation of tumor rates must be made from test animals to humans. A discussion of techniques for interspecies scaling of dose is presented. The use of pharmacokinetics and physiologically based pharmacokinetic models to replace the administered dose with an effective target tissue dose is incorporated for improved risk estimates. Finally, in most bioassays the animals are exposed to a potential carcinogen throughout their lifetime. Exposures of humans to some carcinogens may be for relatively brief periods of time. Procedures for estimating cancer risks for short-term exposures from lifetime bioassays are presented.