Extrapolation of animal carcinogenicity data: limitations and pitfalls.

Laboratory-generated animal bioassay data often serve as the basis for estimating potential human cancer risk. However, there is no single procedure that has been universally accepted as the method of choice for extrapolating experimentally observed results to the low exposure levels that are generally of public health concern. All of the models proposed to date suffer from various limitations. Therefore, the most prudent approach may be to rely primarily on the more conservative procedures such as linear extrapolation until a better understanding of the biological mechanisms underlying the process of carcinogenesis is attained. In addition to the choice of an extrapolation model, there are a variety of other factors, such as the incorporation of background cancer rates, the potential for synergistic reactions, differential pharmacokinetic effects and differences in exposure regimen, that can have a significant bearing on the extrapolation of animal carcinogenicity data to man.