Carcinogenic Risk Assessment with Time-Dependent Exposure Patterns

Previous applications of carcinogenic risk assessment using mathematical models of carcinogenesis have focused largely on the case where the level of exposure remains constant over time. In many situations, however, the dose of the carcinogen varies with time. In this paper, we discuss both the classical Armitage-Doll multistage model and the Moolgavkar-Venzon-Knudson two-stage birth-death-mutation model with time-dependent dosing regimens. Bounds on the degree of underestimation of risk that can occur through the use of a simple time-weighted average dose are derived by means of comparison with an equivalent constant dose corresponding to the actual risk under the time-dependent dosing regimen.