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3. HEALTH EFFECTS
standardized mortality ratio [SMR]=96; 95% CI: 1.26–536). Similarly the lower 95% confidence limit
on the mortality rate ratio for bone cancer was >1. Standard mortality ratios and mortality rate ratios for
other deaths were not statistically significant.
A larger cohort study was examined for cancer mortality in Los Alamos workers (n=15,527 males)
employed at the facility during the period 1943–1973 (Wiggs et al. 1994).
From this larger cohort, a
subset (n=3,775) had been monitored for plutonium exposure and, on that basis, were identified as
plutonium workers in the study. Mortality incidence rates for plutonium workers who were estimated to
have internal plutonium depositions ≥74 Bq (n=303) were compared to workers with depositions <74 Bq
(n=3,472). Cancer mortality rate ratios were not statistically significant (e.g., all cancers, cancers of the
respiratory tract or lung, bone, or lymphopoietic and hematopoietic systems).
Workers at the Hanford plutonium production and processing facility have
been examined for possible
associations between cancer mortality and exposure to ionizing radiation (Gilbert et al. 1989b; Wing and
Richardson 2005; Wing et al. 2004). Gilbert et al. (1989b) examined mortality in association with
external radiation exposure and internal plutonium among workers at the Hanford plant. From the total
cohort of workers (n=31,500), a subset of workers who had confirmed plutonium depositions (n=457)
were identified. The cohort was stratified into exposure categories based internal depositions relative the
maximum permissible body burden (MPBB) at that time (1,480 Bq): no evidence of deposition,
deposition <5% of MPBB (<74 Bq), or deposition ≥5% of MPBB. Approximately 30% of the confirmed
depositions were between 5 and 99% of the MPBB (74–1,465 Bq) and 1.3% were ≥100% of the MPBB.
The study found no evidence for statistically significant excess cancer mortality or trends in cancer
mortality with external radiation or Pu internal deposition (i.e., for all cancers, or cancers of the digestive
tract, lung, lymphatic and hematopoietic tissues, or prostate). Wing et al. (2004) examined
mortality in
association with duration of engagement in plutonium-associated jobs as a surrogate for plutonium
exposure or dose estimates. From the total cohort of workers (n=26,389), subsets of workers who had
activities in routine plutonium-associated jobs (n=3,065) or nonroutine jobs (n=8,266) were identified (of
these, only 377 had confirmed systemic plutonium deposition). Workers in the plutonium-associated jobs
category had lower death rates from all cancers, cancers of the lung, and “plutonium-cancers” (lung, liver,
bone, and connective tissue) than other Hanford workers. However, a significant trend for increased
mortality from nonexternal causes of death with increasing duration at routine plutonium-associated jobs
was observed (1.1% increase in mortality per year, standard error [SE]=0.06).
When stratified by age, the
trend was stronger among workers ≥50 years of age (2.0±1.1% per year), compared to ages <50 years
(0.1±0.9% per year). The strongest trend was for lung cancer (7.1±3.4% per year).
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3. HEALTH EFFECTS
Studies in Animals.
Consistent with findings from human epidemiological studies, results of animal
studies show that tissue location of plutonium-induced cancer is compound dependent. Compound-
related differences in cancer location reflect differences in distribution of plutonium following inhalation;
a significant amount of plutonium from the relatively soluble
238
PuO
2
and
239
Pu(NO
3
)
4
compounds is
distributed to bone and liver. In contrast, the relatively insoluble
239
PuO
2
is primarily retained within the
lungs and associated lymph nodes (DOE 1987f, 1988a), with approximately 10, <1, 0.2, and 0.002%
relocating to liver, skeleton, spleen,
and kidney, respectively (Muggenburg et al. 2008) (see Section 3.4,
Toxicokinetics). Experiments in the ITRI and PNL dogs provide the most extensive database on
radiation-induced cancer following inhalation exposure to plutonium. Information on plutonium-induced
cancer as a primary cause of death is reviewed in Section 3.2.1.1.
In addition, Muggenburg et al. (2008) provided evidence against the “hot particle” theory, which
hypothesized that larger particles with higher activity and less uniform distribution might be more likely
to cause cancer than smaller, more uniformly dispersed particles. The authors exposed dogs to three
uniform sizes of plutonium particles (0.75, 1.5, and 3.0 µm AMAD, representing activities
spanning more
than 2 orders of magnitude from 0.048 to 7.7 mBq) and conducted a composite lifespan study. They
found that smaller and more uniformly distributed particles have the same or greater potential to produce
neoplasms than less uniformly distributed larger particles.
Exposure of Dogs to
238
PuO
2
.
Bone tumors (predominantly osteosarcomas) were the primary cause of
cancer deaths in dogs exposed once to
238
PuO
2
aerosols; lung tumor incidences were also relatively high
in these dogs and liver tumors appeared to be a contributing cause of death in a few
238
PuO
2
-exposed dogs
(Muggenburg et al. 1996; Park et al. 1997). In the ITRI study (Muggenburg et al. 1996), initial
238
Pu lung
burdens ranged from 0.15 to 43.1 kBq/kg. Incidences of bone, lung, and
liver tumors as the cause of
death were 93/144, 36/144, and 2/144 dogs, respectively. The tumors appeared beginning at about
3 years postexposure; liver tumors appeared later than bone and lung tumors. In the PNL study (Park et
al. 1997), mean initial
238
Pu lung burdens ranged from 0.01 to 18.9 kBq/kg. Incidences of bone, lung, and
liver tumors were 34/116 (29%), 31/116 (27%), and 8/116 (7%), respectively.
More deaths were due to
bone tumors than lung tumors, although the average cumulative alpha radiation dose to the lung was
higher than that to the skeleton. Bone tumors occurred more frequently in the axial skeleton than in the
appendicular skeleton (Park et al. 1997). One of 20 control dogs was euthanized due to lung tumors and
1 control dog had a nonfatal liver tumor. Most lung tumors in the
238
PuO
2
-exposed
ITRI and PNL dogs
were located in peripheral lung, rather than central airways, and the majority were classified as