Enhancing low-dose risk assessment using mechanistic mathematical models of radiation effects

Mechanistic mathematical modeling of ionizing radiation (IR) effects has a long history spanning several decades. Models that mathematically represent current knowledge and hypotheses about how radiation damages cells and organs, leading to deleterious outcomes such as carcinogenesis, are particularly useful for estimating radiation risks at doses that are relevant for radiation protection, but are too low to provide a strong 'signal-to-noise ratio' in epidemiological or experimental studies with realistic sample sizes. Here, I discuss examples of models in several relevant areas, including radionuclide biokinetics, non-targeted IR effects, DNA double-strand break (DSB) rejoining and radiation carcinogenesis. I do not provide a detailed review of the vast modeling literature in these fields, but focus on concepts that we have implemented, such as using continuous probability distributions of exponential rates to model radionuclide biokinetics and DSB rejoining, and combining short and long time scales in carcinogenesis models. Improvements in models, including the ability to generate new hypotheses based on model predictions, may come from the introduction of additional novel concepts and from integrating multiple data types. (paper)