33
PLUTONIUM
3. HEALTH EFFECTS
Table 3-2. Summary of Human Epidemiology Studies of Health Effects of
Plutonium
Reference, study location,
period, and study description Dose measurement
a
Findings and interpretation
Reference: Omar et al. 1999
Period: 1947–1992
Design: retrospective cohort
Subjects: workers at Sellafield plant
(n=14,319, 2,689 females) who were
employed at any time during the
period 1947–1975; plutonium worker
cohort consisted of 5,203 workers
ever monitored for plutonium
exposure
Outcome measures: mortality and
cancer morbidity
Analysis: mortality and morbidity
incidence (1971–1986) in plutonium
workers compared to other radiation
and non-radiation workers
Cumulative Pu exposure:
Exposure (Bq) Percent
0–250
75
>250–500
13
>500–750
7
>750–1,000
2
>1,000
3
Pu internal radiation dose
(mean) :
Tissue
Dose (Sv)
Bone surfaces 3,282
Lungs
45–896
Liver
421
Digestive tract 8
Whole body 219–355
Significant (*p<0.01; **p<0.05) MRR for
plutonium workers compared to other radiation
workers (CIs not reported). Significant
negative trend for deaths from all cancers with
internal plutonium plus external radiation
doses (trend tests for internal plutonium doses,
alone, were not reported). No other significant
dose trends.
Category
MRR
All cancers
1.05
Breast cancer
7.66*
Not cancer
0.98
Cerebrovascular disease 1.27**
Respiratory tract disease 0.88
Digestive system disease 0.60**
a
1 kBq=0.027
Ci; 1Gy=100 rad; 1 Sv=100 rem
CI = confidence interval; df = degrees of freedom; DL = detection limit; ERR = excess relative risk; LRT = likelihood
ratio test; MRR = mortality and/or morbidity rate ratio; OR = odds ratio; RR = relative risk; SE = standard error
34
PLUTONIUM
3. HEALTH EFFECTS
these studies provide evidence for an association between cancer mortality (bone, liver, lung) and
exposure to plutonium. Plutonium dose-response relationships for lung cancer mortality and morbidity
have been corroborated in four Mayak studies (Gilbert et al. 2004; Jacob et al. 2005; Kreisheimer et al.
2003; Sokolnikov et al. 2008). 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
(Gilbert et al. 2004); (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 (Sokolnikov et al. 2008); (3) 4.50 per Gy (95% CI: 3.15–6.10) in
males (Kreisheimer et al. 2003); and (4) 0.11 per Sv (95% CI: 0.08–0.17) or 0.21 per Sv (95% CI: 0.15–
0.35) (Jacob et al. 2005), 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 excess relative risk per Gy in Mayak workers declined strongly with attained age
(Gilbert et al. 2004).
The risks of mortality and morbidity from bone and liver cancers have also been studied in Mayak
workers (Gilbert et al. 2000; Koshurnikova et al. 2000; Shilnikova et al. 2003; Sokolnikov et al. 2008;
Tokarskaya et al. 2006). 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 estimate for females was 66 (95%
CI: 16–45), while for males, it was lower at 9.2 (95% CI: 3.3–23; Gilbert et al. 2000). 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; Koshurnikova et al. 2000). Risks of
leukemia mortality in the same cohort were not associated with internal plutonium exposure (Shilnikova
et al. 2003). 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 per Gy (95% CI: 4.6–333) for the dose group >2.0–5.0 Gy and 62.5 per
Gy (95% CI: 7.4–500) for the dose group >5.0–16.9 Gy. Doses were estimated based on periodic urine
sampling (Tokarskaya et al. 2006). Sokolnikov et al. (2008) 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.
35
PLUTONIUM
3. HEALTH EFFECTS
Epidemiological studies of cancer mortality and morbidity are described in detail in the discussion of
cancer from inhaled plutonium (Section 3.2.1.7).
Studies in Animals.
Exposure of Dogs to
238
PuO
2
.
Decreased survival of dogs following inhalation of
238
PuO
2
was observed
in the ITRI and PNL studies (Muggenburg et al. 1996; Park et al. 1997). In both studies, postexposure
survival decreased with increasing initial
238
Pu lung burden. In the ITRI study, survival appeared to
decrease in dogs exposed to
238
PuO
s
aerosols at a median initial lung burden as low as 0.36 kBq/kg body
weight, although it was most apparent at median initial lung burdens ≥1.05 kBq/kg (Muggenburg et al.
1996). At a mean initial lung burden of 23.7 kBq/kg, mean postexposure survival was only 1,316 days
(range: 536–1,517 days), whereas mean survival of vehicle-exposed controls was 4,580 days (range:
3,694-5,694 days). In the
238
PuO
2
-exposed dogs at PNL, mean initial lung burdens ranged from 0.01 to
18.9 kBq/kg body weight and survival was decreased at all levels, but statistically significantly decreased
only at mean initial lung burdens ≥1.17 kBq/kg (Park et al. 1997). Radiation pneumonitis, lung tumors,
bone tumors, and liver tumors were competing causes of death in the
238
PuO
2
-exposed dogs of both ITRI
and PNL (Muggenburg et al. 1996; Park et al. 1997).
Exposures of Dogs to
239
PuO
2
.
Premature death was also observed in dogs exposed to aerosols of
239
PuO
2
. In the ITRI studies, a dose-related decrease in mean survival time was observed, with survival
time inversely related to initial lung burden (Hahn et al. 1999; Muggenburg et al. 1999, 2008). Decreased
postexposure survival was evident at a median initial lung burden as low as 0.63 kBq/kg. Survival ranged
from 152 to 5,941 days in dogs with initial lung burdens between 1 and 10 kBq/kg. At the highest
median initial lung burden (29 kBq/kg), postexposure survival times were as short as 105–1,525 days
compared to 1,893–6,308 days in aerosol vehicle-exposed controls. In the PNL dogs, survival times were
decreased at mean initial lung burdens ≥1 kBq/kg body weight (DOE 1988a; Weller et al. 1995b).
Radiation pneumonitis/interstitial fibrosis and lung tumors were the primary cause of premature death in
ITRI and PNL dogs highly exposed to
239
PuO
2
aerosols. The first two effects are shown together since
the inflammation from radiation pneumonitis is constant due to long-term plutonium retention, and long-
term inflammation always resulted in interstitial fibrosis.
Exposures of Dogs to
239
Pu(NO
3
)
4
. Decreased survival was observed in PNL dogs exposed to aerosols of
239
Pu(NO
3
)
4
resulting in initial lung burdens ≥1.02 kBq/kg body weight (DOE 1986b, 1988b; Park et al.
1995). In the highest exposure group (mean initial lung burden 18.83 kBq/kg), death due to radiation
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