Registry of Plutonium-induced Lung Fibrosis in a Russian Nuclear Worker Cohort

Azizova, Tamara V.; Moseeva, M. B.; Grigoryeva, E. S.; Zhuntova, G.V.; Банникова, М. В.; Sychugov, G. V.; Kazachkov, E. L.

doi:10.1097/hp.0000000000001131

Cited by 15 publications

(6 citation statements)

References 14 publications

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“…Among those workers who could have been exposed to combined radiation (externally to gamma rays and internally to alpha particles) but had not been monitored, 66.3% (40.4%/77.2%) of the workers started employment at the Mayak PA between 1949 and 1959 and potentially could have received non-trivial (high) alpha doses from internal exposure. Here it should also be noted that some of these workers had died of plutonium-induced pulmonary fibrosis (Azizova et al 2019a) while some others had left the city before alpha exposure monitoring was implemented at the Mayak PA. Associated weaknesses of the study are uncertainties in alpha doses due to inaccuracies in bioassay alpha activity measurements and biases inherent to biokinetic and dosimetry models used to estimate alpha doses. These weaknesses limiting all studies of the Mayak PA worker cohort were pointed out in a number of previous papers.…”

Section: Comparison With Other Studiesmentioning

confidence: 99%

Mortality from various diseases of the circulatory system in the Russian Mayak nuclear worker cohort: 1948–2018

et al. 2022

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The paper reports on findings of the study of mortality from diseases of circulatory system (DCS) in Russian nuclear workers of the Mayak Production Association (22,377 individuals with 25.4% of females) who were hired at the facility in 1948–1982 and followed up until end-2018. Using the AMFIT module of EPICURE software, relative risks and excess relative risks per unit absorbed dose (ERR/Gy) for the entire Mayak cohort, the subcohort of workers who were residents of the dormitory town of Ozyorsk and the subcohort of migrants from Ozyorsk were calculated based on maximum likelihood. The mean cumulative liver absorbed gamma-ray dose from external exposure was 0.45 (0.65) Gy (mean (standard deviation) gray) for males and 0.37 (0.56) Gy for females. The mean cumulative liver absorbed alpha dose from internal exposure to incorporated plutonium was 0.18 (0.65) Gy for males and 0.40 (1.92) Gy for females. By the end of the follow-up, 6019 deaths from DCS as the main cause of death were registered among Mayak PA workers (including 3828 deaths in the subcohort of residents and 2191 deaths in the subcohort of migrants) over 890,132 (622,199/267,933) person-years of follow-up. The linear model that took into account non-radiation factors (sex, attained age, calendar period, smoking status and alcohol drinking status) and alpha radiation dose (via adjusting) did not demonstrate significant associations of mortality from DCS, ischemic heart disease (IHD) and cerebrovascular disease (CeVD) with gamma-ray exposure dose in the entire cohort, the resident subcohort and the migrant subcohort (either in males or females). For the subcohort of residents, a significant association with gamma dose was observed for mortality from ischemic stroke in males with ERR/Gy=0.43 (95% CI 0.08; 0.99); there were no significant associations with liver absorbed gamma dose for any other considered outcomes. As for internal exposure, for males no significant associations of mortality from any of the DCS with liver absorbed alpha dose were observed, but for females positive associations were found for DCS (the entire cohort and the resident subcohort) and IHD (the entire cohort) mortality. No significant associations of mortality from various types of DCS with neutron dose were observed either in males or females, although neutron absorbed doses were recorded only in 18% of the workers.

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Section: Comparison With Other Studiesmentioning

confidence: 99%

Mortality from various diseases of the circulatory system in the Russian Mayak nuclear worker cohort: 1948–2018

et al. 2022

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“…It appears that there is some dose threshold for pulmonary fibrosis, but estimates of this threshold vary by orders of magnitude, ranging from 0.5 Gy (10 Sv) (Newman et al 2005) to 6 Gy (Scott and Peterson 2003). The largest cohort of plutonium workers diagnosed with PuLF comes from the early days of the Mayak plutonium production facility, where 188 workers were diagnosed with PuLF (Azizova et al 2020). Of these, 54 cases were of combined etiology (plutonium exposure plus exposure to other toxins or risk factors), and for six workers, PuLF was a primary cause of death.…”

Section: Discussionmentioning

confidence: 99%

“…Of these, 54 cases were of combined etiology (plutonium exposure plus exposure to other toxins or risk factors), and for six workers, PuLF was a primary cause of death. The total radiation dose threshold for lung fibrosis is reported to be 4.0 Gy, although approximately 20% of workers with 1–3 Gy to the lungs from incorporated Pu were diagnosed with PuLF (Azizova et al 2020). In this cohort, it was found that the absorbed dose to the alveoloar-interstitial regions of the respiratory tract was a much better predictor of PuLF than the average absorbed dose to the whole lung.…”

Section: Discussionmentioning

confidence: 99%

Localized Instantaneous Dose Rates from Inhaled Particles of 239Pu

2022

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In this work, the authors present instantaneous local dose rates from particles of plutonium-239 oxide ( 239 PuO) embedded in various regions of the respiratory tract. For comparison, a small number of simulations were performed in a representative region of the respiratory tract with other chemical compounds including pure metallic 239 Pu, 239 PuO 2 , 239 PuO 3 , 239 Pu 2 O 3 , and 239 Pu(NO 3 ) 4 . A small number of simulations were also performed with 238 PuO, weapons grade Pu, and Pu from a typical radioisotope thermoelectric generator (RTG) source for the same reason. The self-shielding effect is minor for very small particles but gradually becomes more significant as the particle size increases. For particles that are 0.1 mm and larger (excluding Pu nitrate), the calculated dose rate within several microns of the particle may be sufficient to damage lung cells, but the implications of damage to such a small volume of tissue are unclear. However, it is reasonable to assume that clinical effects will be observed if a large enough volume of tissue is damaged, as might happen when large numbers of particles are inhaled. The instantaneous dose rate around a particle may be predictive of deterministic effects, scar tissue formation, and biokinetics.

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“…In all 66 cases, the incorporated internal lung dose exceeded 4.0 Gy. Similarly, Azizova et al (2020) reported on a registry of 188 cases of plutonium-induced lung fibrosis among the Mayak worker cohort, and found that the incidence of lung fibrosis was associated with the cumulative lung absorbed dose from internally deposited alpha particles. A retrospective study of 326 plutonium-exposed and 194 unexposed Rocky Flats Plant nuclear workers (Newman et al 2005) The long-term retention of plutonium in the upper respiratory tract of USTUR Case 0269 can be explained by an assumption of a small bound fraction (Puncher et al 2017a, Birchall et al 2019.…”

Section: Literature Reviewmentioning

confidence: 93%

“…In addition to lung cancer, radiationinduced lung fibrosis-development of scar tissues in the connective tissue framework of the lungs-have been observed in experimental animals (Park et al 1964, Bair et al 1980, Sanders et al 1993, Wilson 2009, Nielsen et al 2012 and humans (Newman et al 2005, Azizova et al 2020Romanov et al 2020) in cases of large plutonium intakes. The deterministic effects such as lung fibrosis are expected to occur at doses beyond specific thresholds, and are more severe with larger absorbed doses (Scott and Peterson 2003, Newman et al 2005, Wilson 2009, Park et al 2012, Azizova et al 2020. The amounts and patterns of dose received by different lung tissues depend on retention time and location of plutonium in the lung, which in turn, are functions of several deposition, dissolution, and clearance parameters.…”

Section: Introductionmentioning

confidence: 99%

Modelling of long-term retention of high-fired plutonium oxide in the human respiratory tract: importance of scar-tissue compartments

Poudel¹,

Avtandilashvili²,

Klumpp³

et al. 2021

J. Radiol. Prot.

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The U.S. Transuranium and Uranium Registries whole-body tissue donor Case 0407 had an acute intake of ‘high-fired’ plutonium oxide resulting from a glove-box fire in a fabrication plant at a nuclear defence facility. The respiratory tract of this individual was dissected into five regions (larynx, bronchi, bronchioles, alveolar-interstitial, and thoracic lymph nodes) and analysed for plutonium content. The activities in certain compartments of the respiratory tract were found to be higher than expected from the default models described in publications of the International Commission on Radiological Protection. Because of the extremely slow rate of dissolution of the material inhaled, the presence of bound fraction is incapable of explaining the higher-than-expected retention. A plausible hypothesis—encapsulation of plutonium in scar tissues—is supported by the review of literature. Therefore, scar-tissue compartments corresponding to the larynx, bronchi, bronchioles and alveolar-interstitial regions were added to the existing human respiratory tract model structure. The transfer rates between these compartments were determined using Markov Chain Monte Carlo analysis of data on urinary excretion, lung counts and post-mortem measurements of the liver, skeleton and regional retention in the respiratory tract. Modelling of the data showed that approximately 30% of plutonium activity in the lung was sequestered in scar tissues. The dose consequence of such sequestration is qualitatively compared against that of chemical binding.

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Registry of Plutonium-induced Lung Fibrosis in a Russian Nuclear Worker Cohort

Cited by 15 publications

References 14 publications

Mortality from various diseases of the circulatory system in the Russian Mayak nuclear worker cohort: 1948–2018

Mortality from various diseases of the circulatory system in the Russian Mayak nuclear worker cohort: 1948–2018

Localized Instantaneous Dose Rates from Inhaled Particles of 239Pu

Modelling of long-term retention of high-fired plutonium oxide in the human respiratory tract: importance of scar-tissue compartments

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