Toxicological Profile for Plutonium

11 
PLUTONIUM 
2.  RELEVANCE TO PUBLIC HEALTH 
correspond to 2.2 or 4.3 per Gy, respectively, assuming a radiation weighting factor of 20 for -radiation). 
The ERR per Gy in Mayak workers declined strongly with attained age.  In a recent cohort mortality 
study of the Mayak workers, significant plutonium dose-response relationships (p<0.001) were found for 
deaths due to lung or liver cancer, and for deaths in which bone cancer was considered a contributing 
cause.  At attained age of 60 years, ERRs for lung cancer were 7.1 per Gy (95% CI:  4.9–10) in males and 
15 per Gy (95% CI:  7.6–29) in females.  Averaged-attained age ERRs for liver cancer were 2.6 per Gy 
(95% CI:  0.7–6.9) for males and 29 per Gy (95% CI:  9.8–95) for females, and averaged-attained age 
ERRs for bone cancer were 0.76 per Gy (95% CI:  <0–5.2) for males and 3.4 per Gy (95% CI:  0.4–20) 
for females.  Elevated risks for bone cancer were observed only for workers with plutonium doses 
exceeding 10 Gy.  For lung and bone cancer, the ERR declined with attained age, and for lung cancer, the 
ERR declined with age at first plutonium exposure. 
Decreased survival was noted in beagle dogs exposed to plutonium aerosols (
238
PuO
2
, 
239
PuO
2
, or 
239
Pu(NO
3
)
4
) at levels resulting in initial lung burdens in the range of ≥1 kBq/kg body weight.  Early 
deaths were attributed to radiation pneumonitis and decreased survival late in life was typically associated 
with tumor development. 
Cancer. 
Possible associations between exposure to plutonium and cancer mortality and morbidity have 
been examined in studies of workers at the U.S. plutonium production and/or processing facilities 
(Hanford, Los Alamos, Rocky Flats), as well as facilities in Russia (Mayak) and the United Kingdom 
(e.g., Sellafield).  Compared to studies of U.K. and U.S. facilities, the Mayak cohorts had relatively high 
uptakes of plutonium (i.e., mean body burdens as high as 9.2 kBq, with much higher individual uptakes 
[up to 470 kBq] in relatively large numbers of these workers).  Collectively, the Mayak studies provide 
evidence for an association between cancer mortality (lung, liver, bone) and uptake of plutonium.  Studies 
of U.K. and U.S. facilities have examined cohorts of workers who had substantially lower estimated 
plutonium uptakes and corresponding internal radiation doses than the Mayak cohorts (e.g., Sellafield: 
≤1 kBq in 97% of the assessed workers; Los Alamos:  mean body burden 0.970 kBq, range 0.05– 
3.18 kBq).  Although a significantly higher incidence of cancer mortality in certain groups of plutonium 
workers has been found in some studies, higher cancer incidence and/or risks for tissues that received the 
highest plutonium radiation doses (i.e., lung, liver, bone) have not been found, making causal connections 
of these outcomes to plutonium exposure more uncertain.  The Sellafield study is by far the strongest of 
these studies and did not find associations between plutonium exposure and cancers to tissues receiving 
the highest radiation doses from plutonium. 

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12 
PLUTONIUM 
2.  RELEVANCE TO PUBLIC HEALTH 
Plutonium dose-response relationships for lung cancer mortality and morbidity have been corroborated in 
four Mayak studies.  Estimated excess relative risk in these four studies (adjusted for smoking) were as 
follows:  (1) 3.9 per Gy (95% CI:  2.6–5.8) in males and 19 per Gy (95% CI:  9.5–39) in females; 
(2) 7.1 per Gy (95% CI:  4.9–10) in males and 15 per Gy (95% CI:  7.6–29) in females at attained age of 
60 years; (3) 4.50 per Gy (95% CI:  3.15–6.10) in males; and (4) 0.11 per Sv (95% CI:  0.08–0.17) or 
0.21 per Sv (95% CI:  0.15–0.35), depending on the smoking-radiation interaction model that was 
assumed (these estimates per Sv correspond to 2.2 or 4.3 per Gy, respectively, assuming a radiation 
weighting factor of 20 for "-radiation). 
The risks of mortality and morbidity from bone and liver cancers have also been studied in Mayak 
workers.  Increasing estimated plutonium body burden was associated with increasing liver cancer 
mortality, with higher risk in females compared to males.  Relative risk for liver cancer for a cohort of 
males and females was estimated to be 17 (95% CI:  8.0–26) in association with plutonium uptakes 
>7.4 kBq; however, when stratified by gender, the relative risk estimates for females was 66 (95% CI:  
16–45) and higher than for males, 9.2 (95% CI:  3.3–23).  Risk of bone cancer mortality in this same 
cohort (n=11,000) was estimated to be 7.9 (95% CI:  1.6–32) in association with plutonium uptakes 
>7.4 kBq (males and females combined).  Risks of leukemia mortality, in the same cohort, were not 
associated with internal plutonium exposure.  In a case control study of Mayak workers, the odds ratio for 
liver cancer was 11.3 (95% CI:  3.6–35.2) for subjects who received doses >2.0–5.0 Gy (relative to 0– 
2.0 Gy) and the odds ratios for hemangiosarcomas were 41.7 (95% CI:  4.6–333) for the dose group >2.0– 
5.0 Gy, and 62.5 (95% CI:  7.4–500) for the dose group >5.0–16.9 Gy; doses were estimated based on 
periodic urine sampling.  A study reported averaged-attained age ERRs for liver cancer of 2.6 per Gy 
(95% CI:  0.7–6.9) for males and 29 per Gy (95% CI:  9.8–95) for females, and averaged-attained age 
ERRs for bone cancer of 0.76 per Gy (95% CI:  <0–5.2) for males and 3.4 per Gy (95% CI:  0.4–20) for 
females.  Elevated risks for bone cancer were observed only for workers with plutonium doses exceeding 
10 Gy.  For lung and bone cancer, the ERR declined with attained age, and for lung cancer, the ERR 
declined with age at first plutonium exposure. 
Consistent with findings from human epidemiological studies, results of animal studies show that tissue 
location of plutonium-induced cancer is compound-dependent.  A significant amount of plutonium from 
relatively soluble 
239
Pu(NO
3
)
4
 and 
238
PuO
2
 (more soluble than 
239
PuO
2
 due to higher specific activity of 
238
Pu compared to 
239
Pu) is distributed to bone and liver.  In contrast, relatively insoluble 
239
PuO
2
 is 
primarily retained in lung and associated lymph nodes, with approximately 10, 1, 0.2, and 0.002% 
relocating to liver, skeleton, spleen, and kidney, respectively.  Bone tumors (predominantly 

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