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Adverse outcome pathways, key events, and radiation risk assessment. 2021

R Julian Preston, and Werner Rühm, and Edouard I Azzam, and John D Boice, and Simon Bouffler, and Kathryn D Held, and Mark P Little, and Roy E Shore, and Igor Shuryak, and Michael M Weil
Office of Air and Radiation, Radiation Protection Division, U.S. Environmental Protection Agency, Research Triangle Park, NC, USA.

The overall aim of this contribution to the 'Second Bill Morgan Memorial Special Issue' is to provide a high-level review of a recent report developed by a Committee for the National Council on Radiation Protection and Measurements (NCRP) titled 'Approaches for Integrating Information from Radiation Biology and Epidemiology to Enhance Low-Dose Health Risk Assessment'. It derives from previous NCRP Reports and Commentaries that provide the case for integrating data from radiation biology studies (available and proposed) with epidemiological studies (also available and proposed) to develop Biologically-Based Dose-Response (BBDR) models. In this review, it is proposed for such models to leverage the adverse outcome pathways (AOP) and key events (KE) approach for better characterizing radiation-induced cancers and circulatory disease (as the example for a noncancer outcome). The review discusses the current state of knowledge of mechanisms of carcinogenesis, with an emphasis on radiation-induced cancers, and a similar discussion for circulatory disease. The types of the various informative BBDR models are presented along with a proposed generalized BBDR model for cancer and a more speculative one for circulatory disease. The way forward is presented in a comprehensive discussion of the research needs to address the goal of enhancing health risk assessment of exposures to low doses of radiation. The use of an AOP/KE approach for developing a mechanistic framework for BBDR models of radiation-induced cancer and circulatory disease is considered to be a viable one based upon current knowledge of the mechanisms of formation of these adverse health outcomes and the available technical capabilities and computational advances. The way forward for enhancing low-dose radiation risk estimates will require there to be a tight integration of epidemiology data and radiation biology information to meet the goals of relevance and sensitivity of the adverse health outcomes required for overall health risk assessment at low doses and dose rates.

UI MeSH Term Description Entries
D011829 Radiation Dosage The amount of radiation energy that is deposited in a unit mass of material, such as tissues of plants or animal. In RADIOTHERAPY, radiation dosage is expressed in gray units (Gy). In RADIOLOGIC HEALTH, the dosage is expressed by the product of absorbed dose (Gy) and quality factor (a function of linear energy transfer), and is called radiation dose equivalent in sievert units (Sv). Sievert Units,Dosage, Radiation,Gray Units,Gy Radiation,Sv Radiation Dose Equivalent,Dosages, Radiation,Radiation Dosages,Units, Gray,Units, Sievert
D011835 Radiation Protection Methods and practices adopted to protect against RADIATION. Protection, Radiation
D011853 Radiobiology Study of the scientific principles, mechanisms, and effects of the interaction of ionizing radiation with living matter. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Radiation Biology,Biology, Radiation
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000073931 Adverse Outcome Pathways Models connecting initiating events at the cellular and molecular level to population-wide impacts. Computational models may be at levels relating toxicology to adverse effects. Adverse Outcome Pathway
D018570 Risk Assessment The qualitative or quantitative estimation of the likelihood of adverse effects that may result from exposure to specified health hazards or from the absence of beneficial influences. (Last, Dictionary of Epidemiology, 1988) Assessment, Risk,Benefit-Risk Assessment,Risk Analysis,Risk-Benefit Assessment,Health Risk Assessment,Risks and Benefits,Analysis, Risk,Assessment, Benefit-Risk,Assessment, Health Risk,Assessment, Risk-Benefit,Benefit Risk Assessment,Benefit-Risk Assessments,Benefits and Risks,Health Risk Assessments,Risk Analyses,Risk Assessment, Health,Risk Assessments,Risk Benefit Assessment,Risk-Benefit Assessments

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