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Purpose: This review is a contribution to the memory of Dr William (Bill) Morgan and highlights an area of research and deliberation that he considered extremely important in support of the setting of protective radiation dose limits. Biological research has generally played a minor role in the estimation of adverse health outcomes following exposure to low doses and low dose rates of radiation. The reliance has been on the available, quite extensive data base of epidemiology studies. The major concern is that such studies are for moderate to high doses requiring risk extrapolation methodologies for estimating low dose effects. There are significant uncertainties associated with this approach. This review will discuss how radiation biology studies can potentially reduce this uncertainty through the use of a key events/adverse outcome pathways approach to identify bioindicators of cancer and non-cancer effects for use as parameters in biologically-based dose-response (BBDR) models. Such models would allow for an improved extrapolation approach for estimating health effects at low doses and low dose rates of radiation.

Conclusion: Based on reported and ongoing studies for environmental chemicals, the adverse outcome/key events approach is a viable one for enhanced risk assessment (and risk management practice). The identification of informative bioindicators of adverse health effects will be a challenge but with modern molecular and advanced computational techniques, it is certainly feasible. This approach provides a framework for defining a low dose radiation research program; something that was of great importance to Bill Morgan.