PRINCIPLES OF TOXICOLOGY

18.4 DOSE–RESPONSE ASSESSMENT 457
Figure 18.6 Four different extrapolation models applied to the same experimental data. All fit the data equally
well in the observable range, but each yields substantially different risk estimates in the low-dose region most
applicable to occupational and environmental exposures. [Adapted from NRC (1983).]
threshold for even those carcinogens whose mechanism is believed to involve some mutational event
or other form of genetic damage. Thus, it is widely held today that thresholds exist for many
carcinogens, and that cancer risk assessment for these chemicals should be conducted using threshold
dose–response models similar to those used for noncancer effects.
In recent years, debates involving the actual shape of the dose–response curve for carcinogens in
the low-dose region, and the issue of thresholds for carcinogens, have caused scientists and regulatory
agencies to reevaluate earlier cancer risk assessment methodologies. Out of this reevaluation has come
a movement to adopt two major policy changes in the cancer risk assessment methodologies employed
by regulatory agencies. One proposed change is to use risk extrapolation models that make fewer
assumptions about the shape of the dose–response curve (e.g., the benchmark dose and margin-ofexposure
method). Data within the observation range can be used to develop a “point of departure,”