Vol. 8, 2023

Radiation Protection

A CONTRIBUTION TO THE CURRENT DEBATE ABOUT THE ADEQUACY OF THE LINEAR-NO-THRESHOLD (LNT) MODEL FOR THE RISK RESULTING FROM RADON EXPOSURE

J. Elío, M. Janik, P. Bossew

Pages: 65-74

DOI: 10.37392/RapProc.2023.14

The Linear-No Threshold Hypothesis (LNT) states that risk from ionizing radiation is linearly related to dose with no dose threshold below which there was no risk. The LNT is an important fundament in practical radioprotection and for assessment of population risk, e.g., of estimating lung cancer risk or incidence attributable to exposure to indoor radon. The popularity of the LNT stems largely from its mathematical simplicity and therefore, its practicability. It seems that this has obscured the question of whether it is physically true, or “only” a useful practical rule. Distribution of exposure and dose to radon through the population is strongly right-skew, with the bulk of dose low. Therefore, attribution of risk, i.e., mainly lung cancer incidence, depends strongly on the risk model for low dose. As long as no micro-dosimetric model exists which causally relates incident radiation flux or exposure to radon progeny to a sequence of effects, starting on sub-cellular level, which results in clinical evidence, it is impossible to make statements on the effect of very low doses, since it is in principle impossible to extend empirical epidemiological inference to arbitrarily small doses. Therefore, epidemiological findings are extrapolated towards low doses. The most quoted large-scale epidemiological radon meta-study is Darby et al. (2006), which concludes that the LNT model is statistically compatible with the findings. This has been essentially corroborated by newer studies. However, with availability or more data, there seems to be increasing evidence that the model may not be applicable to estimate risk for low doses, which represent the bulk of exposure, if the objective is assessment of population risk. We review literature about the strongly debated question about validity of the LNT. Data are not publicly available, therefore statistical re-analysis is impossible. However, published information in the form of graphs and statistics allows some hypotheses alternative to the LNT. The debate is so serious because of the political consequences regarding radon abatement policy. We refrain from stating any “alternative truth” but investigate the possible consequences for risk assessment and what they entail for radon regulation and policy, resulting from different risk models.
  1. WHO Handbook on Indoor Radon: A Public Health Perspective, WHO, Geneva, Switzerland, 2009.
    Retrieved from: https://www.who.int/publications/i/item/9789241547673
    Retrieved on: Jun. 24, 2023
  2. Radiation Protection and Safety of Radiation Sources: International Basic Safety Standards , Safety Standards No. GSR Part 3, IAEA, Vienna, Austria, 2014.
    Retrieved from: www.pub.iaea.org/MTCD/Publications/PDF/Pub1578_web-57265295.pdf
    Retrieved on: Jun. 24, 2023
  3. The Council of European Union. (Dec. 5, 2013). Council Directive 2013/59/EURATOM on laying down basic safety standards for protection against the dangers arising from exposure to ionising radiation, and repealing Directives 89/618/Euratom, 90/641/Euratom, 96/29/Euratom, 97/43/Euratom and 2003/122/Euratom.
    Retrieved from: http://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=OJ:L:2014:013:FULL&from=EN
    Retrieved on: Jun. 24, 2023
  4. G. Cinelli et al., European Atlas of Natural Radiation, 1st ed., Publication Office of the European Union, Luxembourg, Luxembourg, 2019.
    Retrieved from: https://remon.jrc.ec.europa.eu/About/Atlas-of-Natural-Radiation
    Retrieved on: Jun. 29, 2023
  5. The 2007 Recommendations of the International Commission on Radiological Protection , vol. 37, ICRP Publication no. 103, Ottawa, Canada, 2007.
    Retrieved from: https://www.icrp.org/publication.asp?id=ICRP%20Publication%20103
    Retrieved on: Jun. 28, 2023
  6. D. B. Richardson et al., “Lung Cancer and Radon: Pooled Analysis of Uranium Miners Hired in 1960 or Later,” Environ. Health Perspect., vol. 130, no. 5, 057010, May 2022.
    DOI: 10.1289/EHP10669
    PMid: 35604341
    PMCid: PMC9126132
  7. P. Duan et al., “Nonlinear dose-response relationship between radon exposure and the risk of lung cancer: evidence from a meta-analysis of published observational studies,” Eur. J. Cancer Prev., vol. 24, no. 4, pp. 267 – 277, Jul. 2015.
    DOI: 10.1097/CEJ.0000000000000066
    PMid: 25117725
  8. B. Grosche, M. Kreuzer, M. Kreisheimer, M. Schnelzer, A. Tschense, “Lung cancer risk among German male uranium miners: A cohort study, 1946-1998,” Br. J. Cancer, vol. 95, no. 9, pp. 1280 – 1287, Nov. 2006.
    DOI: 10.1038/sj.bjc.6603403
    PMid: 17043686
    PMCid: PMC2360564
  9. K. Kelly-Reif et al., “Radon and lung cancer in the pooled uranium miners analysis (PUMA): highly exposed early miners and all miners,” Occup. Environ. Med. , vol. 80, no. 7, pp. 385 – 391, Jul. 2023.
    DOI: 10.1136/oemed-2022-108532
    PMid: 37164624
    PMCid: PMC10369304
  10. H. J. Muller, The production of mutations, Nobel Prize organisation, Stockholm, Sweden, 1946.
    Retrieved from: https://www.nobelprize.org/prizes/medicine/1946/muller/lecture/
    Retrieved on: Jun. 25, 2023
  11. E. J. Calabrese, “Muller’s Nobel lecture on dose-response for ionizing radiation: Ideology or science?,” Arch. Toxicol., vol. 85, no. 12, pp. 1495 – 1498, Dec. 2011.
    DOI: 10.1007/s00204-011-0728-8
    PMid: 21717110
  12. S. Darby et al., “Radon in homes and risk of lung cancer: Collaborative analysis of individual data from 13 European case-control studies,” Br. Med. J. , vol. 330, no. 7485, pp. 223 – 226, Jan. 2005,
    DOI: 10.1136/bmj.38308.477650.63
    PMid: 15613366
    PMCid: PMC546066
  13. Sources, effects and risks of ionizing radiation, UNSCEAR 2012 Report to the General Assembly, with Scientific Annexes, UNSCEAR, New York (NY), USA, 2015.
    Retrieved from: https://www.unscear.org/unscear/en/publications/2012.html
    Retrieved on: Jun. 25, 2023
  14. K. Kino et al., “Considering Existing Factors That May Cause Radiation Hormesis at <100 mSv and Obey the Linear No-Threshold Theory at ≥100 mSv,” Challenges, vol. 12, no. 2, 33, Dec. 2021.
    DOI: 10.3390/challe12020033
  15. R. Nilsson, J. Tong, “Opinion on reconsideration of lung cancer risk from domestic radon exposure,” Radiat. Med. Prot., vol. 1, no. 1, pp. 48 – 54, Mar. 2020.
    DOI: 10.1016/j.radmp.2020.01.001
  16. A. M. Block, S. R. Silva, J. S. Welsh, “Low-dose total body irradiation: an overlooked cancer immunotherapy technique,” J. Radiat. Oncol., vol. 6, no. 2, pp. 109 – 115, Jun. 2017.
    DOI: 10.1007/s13566-017-0303-x
  17. Z. Chen, Z. Wu, T. A. Muluh, S. Fu, J. Wu, “Effect of low-dose total-body radiotherapy on immune microenvironment,” Transl. Oncol., vol. 14, no. 8, 101118, Aug. 2021.
    DOI: 10.1016/j.tranon.2021.101118
    PMid: 34020371
    PMCid: PMC8142085
  18. L. Dobrzyński, K. W. Fornalski, J. Reszczyńska, “Meta-analysis of thirty-two case–control and two ecological radon studies of lung cancer,” J. Radiat. Res., vol. 59, no. 2, pp. 149 – 163, Mar. 2018.
    DOI: 10.1093/jrr/rrx061
    PMid: 29186473
    PMCid: PMC5950923
  19. Radiation protection 125: Low dose ionizing radiation and cancer risk , European Commission, Brussels, Belgium, 2001.
    Retrieved from: https://energy.ec.europa.eu/system/files/2014-11/125_0.pdf
    Retrieved on: Jun. 25, 2023
  20. A. Marín et al., “Bystander effects and radiotherapy,” Rep. Pract. Oncol. Radiother. , vol. 20, no. 1, pp. 12 – 21, Jan.-Feb. 2015.
    DOI: 10.1016/j.rpor.2014.08.004
    PMid: 25535579
    PMCid: PMC4268598
  21. M. Tubiana, L. E. Feinendegen, C. Yang, J. M. Kaminski, “The linear no-threshold relationship is inconsistent with radiation biologic and experimental data,” Radiology, vol. 251, no. 1, pp. 13 – 22, Apr. 2009.
    DOI: 10.1148/radiol.2511080671
    PMid: 19332842
    PMCid: PMC2663584
  22. A. Gaziev, G. Shaikhaev, “Limited Repair of Critical DNA Damage in Cells Exposed to Low Dose Radiation,” in Current Topics in Ionizing Radiation Research , M. Nenoi, Eds., Rijeka, Croatia: InTech, ch. 4, 2012, pp. 51 – 80.
    DOI: 10.5772/33611
  23. Optimisation: Rethinking the Art of Reasonable, Workshop Summary Report NEA/CRPPH/R(2020)2, NEA, Paris, France, 2020.
    Retrieved from: https://www.oecd-nea.org/jcms/pl_60901/optimisation-rethinking-the-art-of-reasonable-workshop-summary-report?details=true
    Retrieved on: Jul. 10, 2023
  24. A. Rosenberger et al., “On the non-linearity of radon-induced lung cancer,” deposited at Research Square, Oct. 03, 2022.
    DOI: 10.21203/rs.3.rs-1933741/v2
  25. L. E. Feinendegen, “Evidence for beneficial low level radiation effects and radiation hormesis,” Br. J. Radiol., vol. 78, no. 925, pp. 3 – 7, Jan. 2005.
    DOI: 10.1259/bjr/63353075
    PMid: 15673519
  26. R. E. Thompson, D. F. Nelson, J. H. Popkin, Z. Popkin, “Case-control study of lung cancer risk from residential radon exposure in Worcester County, Massachusetts,” Health Phys., vol. 94, no. 3, pp. 228 – 241, Mar. 2008.
    DOI: 10.1097/01.HP.0000288561.53790.5f
    PMid: 18301096
  27. R. E. Thompson, “Epidemiological evidence for possible radiation hormesis from radon exposure: A case-control study conducted in Worcester, MA,” Dose-Response, vol. 9, no. 1, pp. 59 – 75, 2011.
    DOI: 10.2203/dose-response.10-026.Thompson
    PMid: 21431078
    PMCid: PMC3057636
  28. B. L. Cohen, “A test of the linear-no threshold theory of radiation carcinogenesis,” Environ. Res., vol. 53, no. 2, pp. 193 – 220, Dec. 1990.
    DOI: 10.1016/S0013-9351(05)80119-7
    PMid: 2253600
  29. B. L. Cohen, “Updates and extensions to tests of the linear-no threshold theory,” Technology, vol. 7. pp. 657 – 672, Jan. 2000.
  30. B. L. Cohen, “Test of the Linear-No Threshold Theory: Rationale for Procedures,” Dose-Response, vol. 3, no. 3, pp. 369 – 390, May 2006.
    DOI: 10.2203/dose-response.003.03.007
    PMid: 18648621
    PMCid: PMC2475951
  31. K. Becker, “Health Effects of High Radon Environments in Central Europe: Another Test for the LNT Hypothesis?,” Nonlinearity Biol. Toxicol. Med. , vol. 1, no. 1, pp. 3 – 35, Jan. 2003.
    DOI: 10.1080/15401420390844447
    PMid: 19330110
    PMCid: PMC2651614
  32. E. J. Calabrese, “Hormesis: From marginalization to mainstream. A case for hormesis as the default dose-response model in risk assessment,” Toxicol. Appl. Pharmacol. , vol. 197, no. 2, pp. 125 – 136, Jun. 2004.
    DOI: 10.1016/j.taap.2004.02.007
    PMid: 15163548
  33. C. L. Sanders, Radiation hormesis and the linear-no-threshold assumption , 1st ed., Heidelberg, Germany: Springer-Verlag Berlin Heidelberg, 2010.
    DOI: 10.1007/978-3-642-03720-7
  34. M. K. Janiak, M. P. R. Waligórski, “Can Low-Level Ionizing Radiation Do Us Any Harm?,” Dose-Response, vol. 21, no. 1, pp. 1 – 15, 2023.
    DOI: 10.1177/15593258221148013
  35. S. M. J. Mortazavi, M. Ghiassi-Nejad, M. Rezaiean, “Cancer risk due to exposure to high levels of natural radon in the inhabitants of Ramsar, Iran,” Int. Congr. Ser., vol. 1276, pp. 436 – 437, Feb. 2005.
    DOI: 10.1016/j.ics.2004.12.012
  36. G. R. W. Denton, S. Namazi, “Indoor Radon Levels and Lung Cancer Incidence on Guam,” Procedia Environ. Sci., vol. 18, pp. 157 – 166, 2013.
    DOI: 10.1016/j.proenv.2013.04.021
  37. Radon therapies, German Federal Office for Radiation Protection, Salzgitter, Germany.
    Retrieved from: https://www.bfs.de/EN/topics/ion/environment/radon/effects/therapies.html
    Retrieved on: Jul. 04, 2023
  38. H. Tempfer, A. Schober, W. Hofmann, H. Lettner, F. Steger, “Biophysical mechanisms and radiation doses in radon therapy,” in The Natural Radiation Environment VII , vol. 7, J. P. McLaughlin, S. E. Simopoulos, F. Steinhäusler, Eds., Amsterdam, Netherlands: Elsevier, 2005, ch. 4, sec. 78, pp. 640 – 648.
    DOI: 10.1016/S1569-4860(04)07078-0
  39. A. Falkenbach, J. Kovacs, A. Franke, K. Jörgens, K. Ammer, “Radon therapy for the treatment of rheumatic diseases - Review and meta-analysis of controlled clinical trials,” Rheumatol. Int., vol. 25, no. 3, pp. 205 – 210, Apr. 2005.
    DOI: 10.1007/s00296-003-0419-8
    PMid: 14673618
  40. A. Maier et al., “Radon Exposure—Therapeutic Effect and Cancer Risk,” Int. J. Mol. Sci. , vol. 22, no. 1, 316, Dec. 2020.
    DOI: 10.3390/ijms22010316
    PMid: 33396815
    PMCid: PMC7796069
  41. K. Yamaoka, T. Kataoka, “Confirmation of efficacy, elucidation of mechanism, and new search for indications of radon therapy,” J. Clin. Biochem. Nutr. , vol. 70, no. 2, pp. 87 – 92, Mar. 2022.
    DOI: 10.3164/JCBN.21-85
    PMid: 35400814
    PMCid: PMC8921726
  42. S. Kojima et al., “Radon Therapy Is Very Promising as a Primary or an Adjuvant Treatment for Different Types of Cancers: 4 Case Reports,” Dose-Response , vol. 17, no. 2, pp. 1–9, Jun. 2019.
    DOI: 10.1177/1559325819853163
    PMid: 31210758
    PMCid: PMC6552369
  43. D. Passali, G. Gabelli, G. C. Passali, R. Mösges, L. M. Bellussi, “Radon-enriched hot spring water therapy for upper and lower respiratory tract inflammation,” Otolaryngol. Pol., vol. 71, no. 4, pp. 8 – 13, Aug. 2017.
    DOI: 10.5604/01.3001.0010.2242
    PMid: 29116046
  44. Z. Zdrojewicz, J. J. Strzelczyk, “Radon Treatment Controversy,” Dose-Response , vol. 4, no. 2, pp. 106 – 118, Aug. 2006.
    DOI: 10.2203/dose-response.05-025.zdrojewicz
    PMid: 18648641
    PMCid: PMC2477672
  45. Linear no-threshold model, Wikipedia, the free encyclopedia, San Francisco (CA), USA,
    Retrieved from: https://en.wikipedia.org/wiki/Linear_no-threshold_model
    Retrieved on: Jul. 04, 2023
  46. J. Gaskin, D. Coyle, J. Whyte, D. Krewksi, “Global Estimate of Lung Cancer Mortality Attributable to Residential Radon,” Environ. Health Perspect. , vol. 126, no. 5, 057009, May 2018.
    DOI: 10.1289/EHP2503
    PMid: 29856911
    PMCid: PMC6072010
  47. Occupational Intakes of Radionuclides: Part 3, vol. 46, ICRP Publication no. 137, ICRP, Ottawa, Canada, 2017, pp. 1 – 486.
    Retrieved from: https://www.icrp.org/publication.asp?id=ICRP%20Publication%20137
    Retrieved on: Jun. 29, 2023
  48. J. Elío et al., “The first version of the Pan-European Indoor Radon Map,” Nat. Hazards Earth Syst. Sci., vol. 19, no. 11, pp. 2451 – 2464, Nov. 2019.
    DOI: 10.5194/nhess-19-2451-2019
  49. P. Bossew, “The Geographical Pattern of Local Statistical Dispersion of Environmental Radon in Europe,” Math. Geosci., spec. issue, 2023.
    DOI: 10.1007/s11004-023-10073-x
  50. P. Bossew et al., “Current topic discussions in radon research,” presented at the Int. Conf. Radiation and Applications (RAP 2022), Thessaloniki, Greece, Jun. 2022.
    Retrieved from: https://drive.google.com/file/d/1jqIaOMgq_DrM_4zSKKUfShg8KDzWxlNo/view
    Retrieved on: Jun. 29, 2023
  51. E. Petermann, P. Bossew, B. Hoffmann, “Radon hazard vs. radon risk - On the effectiveness of radon priority areas,” J. Environ. Radioact., vol. 244 – 245, 106833, Apr. 2022.
    DOI: 10.1016/j.jenvrad.2022.106833
    PMid: 35131623
  52. E. Petermann, P. Bossew, “Mapping indoor radon hazard in Germany: The geogenic component,” Sci. Total Environ., vol. 780, 146601, Aug. 2021.
    DOI: 10.1016/j.scitotenv.2021.146601
    PMid: 33774294
  53. E. Petermann, H. Meyer, M. Nussbaum, P. Bossew, “Mapping the geogenic radon potential for Germany by machine learning,” Sci. Total Environ., vol. 754, 142291, Feb. 2021.
    DOI: 10.1016/j.scitotenv.2020.142291
    PMid: 33254926
  54. R. Gellermann, J. Breckow, “LNT und Strahlenschutz,” STRAHLENSCHUTZ Prax. , vol. 1, p. 80f, 2023.
    (R. Gellermann, J. Breckow, “LNT and Radiation Protection,” RADIATION PROTECTION Practice , vol. 1, p. 80f, 2023.)
  55. P. Bossew, E. Petermann, “What is the objective of radon abatement policy? Revisiting the concept of radon priority areas,” presented at the15th Int. workshop on the geological aspects of radon risk mapping (GARRM), Prague, Czech Republic, Sep.2021.
    Retrieved from: http://www.radon.eu/workshop2021/pres/bossew_2021.pdf
    Retrieved on: Jun. 23, 2023
  56. E. Petermann, P. Bossew, N. Suhr, B. Hoffmann, “Estimating national indoor radon exposure at a high spatial resolution – improvements by a machine learning based probabilistic approach,” presented at theEGU 2023, Vienna, Austria, Apr. 2023.
    Retrieved from: https://doi.org/10.5194/egusphere-egu23-6423
    Retrieved on: Jun. 23, 2023
  57. A. Onishchenko, M. Zhukovsky, “The influence of uncertainties of radon exposure on the results of case-control epidemiological study,” Int. J. Radiat. Biol ., vol. 95, no. 3, pp. 354 – 359, Mar. 2019.
    DOI: 10.1080/09553002.2019.1547846
    PMid: 30496022
  58. J. S. Puskin, “Smoking as a confounder in ecologic correlations of cancer mortality rates with average county radon levels,” Health Phys., vol. 84, no. 4, pp. 526 – 532, Apr. 2003.
    DOI: 10.1097/00004032-200304000-00012
    PMid: 12705451