Cancer Modeling with Intermittent Exposures
In this article we consider the application of both the classical Armitage-Doll multi-stage model and the Moolgavkar-Venzon-Knudson two-stage birthdeath-mutation model in situations in which carcinogen exposure is not constant over time. In particular, novel representations of the cumulative hazard function are used to describe the relative effectiveness of dosing at different times, and to establish an equivalent constant dose which leads to the same risk as time-dependent dosing. The relative effectiveness function may be used to establish the degree to which the use of a simple time-weighted average dose may underestimate (or overestimate) risk. Both the Armitage-Doll and Moolgavkar-Venzon-Knudson models are applied to bioassay data on B(a)P with variable dosing patterns, using equivalent constant doses to facilitate maximum likelihood estimation of the model parameters.
KeywordsRelative Effectiveness Cumulative Hazard Cancer Risk Assessment Constant Dose Intermittent Exposure
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