Two‐stage models of tumor incidence for historical control animals in the national toxicology program's carcinogenicity experiments

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Abstract
The tumor incidence rate is modeled for various tumors in a database of control animals [Fischer 344 rats and (C57BL/6 .times. C3H)F1 mice] originally developed by the national Toxicology Program and recently augmented to include additional sacrifice data by Portier et al. (1986). These rates are assumed to follow a clonal two-stage model of carcinogenesis where cells in the various tissues are allowed to be in one of three states arbitrarily defined as a "normal" state, an "initiated" state, and a "tumor present" state. The parameters of this clonal two-stage model have a direct interpretation with regard to the mechanism of action and in some cases may suggest a common mechanism for various tumours in the different sex/species groups. Also, the risk of dying (from all causes) in tumor-bearing animals is compared to the risk of dying in non-tumor-bearing animals via estimates of relative risk. In general, it general, it was found that the risk of dying was elevated for most tumors. The purpose of this analysis is to provide estimates of baseline tumor rates and relative risks, which are useful in the design and analysis of future carcinogenicity experiments.