Estimation of risks of irreversible, delayed toxicity

This report reviews the current statistical methods used (1) to establish dose‐response relationships for irreversible self‐replicating toxic effects (i.e., carcinogenesis) in laboratory animals and (2) to extrapolate these data to man. The method or procedure for estimating human risk based on animal studies is basically carried out in four sequential steps: Design and/or assessment of laboratory experiments as to quality and biological appropriateness. Statistical extrapolation of the experimental results to low dose levels. Extrapolation of the estimated results in animals at the low level to man. Assessment of the risk to man based upon experimental data. Each of these steps is difficult, and the purpose of this report is to review what is known about them and to determine what research is required in order to improve the quality of the total procedure.