Do not waste time and money for AOP: Admitting LNT as a scientific fact is the highest priority for revised general recommendation

Adverse outcome pathway (AOP) analysis is getting attention from radiation researchers. This study aims to examine the validity of AOP in the study of radiation health effects. For this purpose, a bibliometric analysis of previous research on AOP and a quantitative analysis of AOP-Wiki were conducted. A keyword search with ‘adverse outcome pathway’ in Web of Science (WoS) yielded 920 hits in 190 journals. The first article that related AOP to radiological protection was published in Health Physics in 2015 and proposed ‘Integrating Basic Radiobiological Science and Epidemiological Studies’ to reduce the uncertainty in risk estimates. Since that initial proposal, 31 radiation-related AOP articles have been published in four journals. Among them, 21 articles were published in the International Journal of Radiation Biology . Despite the wide range of knowledge necessary to complete links from radiation exposure to population responses, the contribution is biased toward biology. At the OECD AOP-Wiki, 437 AOPs have been registered, but only 29 were endorsed as reliable. Among the 14 radiation-related AOPs, AOP 272, ‘Deposition of energy leading to lung cancer’, reached the most advanced OECD approval status. It registered the following common sense link: ‘Energy deposition (molecular initiating event)’, ‘Increase, DNA strand breaks (KE1)’, ‘Insufficient DNA repair (KE2)’, ‘Increase, mutations (KE3)’, ‘Increase, chromosomal abnormalities (KE4)’, ‘Increase, cell proliferation (KE5)’, ‘Increase, lung cancer (AO)’. According to NCRP's review on radiation epidemiology published in 2018, ‘Most of the larger, stronger studies broadly supported an LNT model’. To explain this relationship, quantitative evaluation is necessary for each chain, for example, the probability of DNA break and repair considering the dependence on location in the organ. However, among the 14 key event relationships, 7 are rated low in quantitative understanding. The unified field theory that aims to integrate quantum mechanics and relativity is far from complete in physics. Integrating biology and epidemiology: A series of events at different levels, from molecular to population, seems impossible in principle. The fact that the OECD hosts the AOP-Wiki, which prioritises economic development rather than public health, causes a conflict of interest concern. In the case of the Minamata disease, despite it being clear that the cause was fish caught in Minamata Bay, the Japanese government did not regulate fishing and distribution of fish because the causality is unclear. Adherence to mechanisms could lead to delays in regulation and more significant health hazards. The LNT model should be confirmed as a scientific fact, and AOP studies should be separated from regulations for radiation protection.