Bone cancer risk of (239)pu in humans derived from animal models

Two-mutation model fits to bone cancer mortality data from mice, rats and beagle dogs injected with (239)Pu or (226)Ra show that (1) it is possible to fit the radiation-related parameters for animals from different strains of the same species together; (2) for every species the same significant parameters are found in the models for (239)Pu and in the models for (226)Ra, and the only difference is in the value of the linear mutation coefficient; and (3) the toxicity ratio, when defined as the ratio of the linear mutation coefficients for (239)Pu over (226)Ra, has a relatively uniform value of approximately 8 for the species considered. This relatively constant ratio enables the development of a (239)Pu model for humans that is based on the radium dial painters and the toxicity ratio for beagles. The model predictions agree well with published risk estimates based on other data and derived using alternative approaches. This has two important implications: (1) The two-mutation model appears to be a useful tool in translating from animal models to humans in a meaningful way; and (2) once a two-mutation model for humans has been derived, radiation risks can be calculated that depend on doses, dose rates and ages at exposure. Such a model therefore supplements published risk estimates that often lack such dependences.