Cancer Risk Evaluation from Animal Studies

Data from properly designed and evaluated studies in experimental animals have been and continue to be reliable sources of information for the identification of potential human health hazards and the estimation of risks in exposed human populations. Properly designed studies must include (a) animal models that are sensitive to the endpoints under investigation, (b) adequately challenging doses, (c) adequate durations of exposure (at least 2 years for carcinogenicity studies in rats and mice), (d) sufficient numbers of animals per dose group to have adequate statistical power to detect a true effect, (e) multiple dose groups to allow characterization of dose–response relationships, (f) complete and peer-reviewed histopathological diagnoses, and (g) pair-wise comparisons with the control group and analyses of trends based on survival-adjusted tumor rates. Mechanistic information and pharmacokinetic models that have been adequately tested may have an impact on the characterization of dose–response relationships and the estimation of cancer risk at human exposure levels. Setting occupational or environmental exposure standards based on animal carcinogenicity data provides a prudent public health approach to reduce the burden of cancer in exposed populations. More work is necessary to understand the basis for interindividual differences in susceptibility and to properly establish health-based exposure standards that protect the most vulnerable segments of the general population. Keywords: cancer bioassay; laboratory animals; human cancer risk; histopathology; statistical power; survival-adjusted tumor rates; low-dose extrapolation; human susceptibility; exposure standards