ABSTRACT
Mathematical modeling of cancer dose-response for the purpose of individualized risk estimation dates back several decades. A major breakthrough in the development of cancer dose-response analysis occurred when the pharmacokinetic information was considered additionally. These models were known as Physiologically Based Pharmacokinetic (PBPK) models. This chapter demonstrates the process of the progression of models by starting with the simple dose-response models and finish by describing the features and properties of the PBPK model. Cancer risk is measured by hazard rate or age-specific incidence rate. The hazard function is defined as the instantaneous rate of change in the probability of cancer incidence. Tolerance distribution models simply express the distribution of individual toxic thresholds in the population. It is assumed that each individual (animal in carcinogenicity experiments) in the population has a tolerance for the carcinogenic chemical. Once the dose exceeds this tolerance limit, the individual develops tumor.
