45
PLUTONIUM
3. HEALTH EFFECTS
et al. 1999, 2008). The time to death from radiation pneumonitis was not different in
ITRI dogs
administered a single exposure (initial lung burden of 3.9 kBq/kg) or repeated exposures (7–10 semi-
annual exposures for a mean total lung burden of 5.3 kBq/kg) (Diel et al. 1992). Death due to radiation
pneumonitis was observed in
239
PuO
2
-exposed PNL dogs at mean initial lung burdens ≥1 kBq/kg (DOE
1988a; Weller et al. 1995b). Histopathologic changes to lungs included interstitial and subpleural
fibrosis, alveolar hyperplasia, and squamous metaplasia. Radiation pneumonitis and
lung cancer were
competing causes of death in dogs that inhaled
239
PuO
2
. The frequencies of both radiation pneumonitis
and lung cancer were the same in dogs receiving an average ILB of 3.7 kBq/kg from
239
PuO
2
. At higher
doses, radiation pneumonitis occurred more frequently to the point that dogs died without signs of cancer
at an average ILB of 29 kBq/kg. At lower doses, cancer occurred more frequently and radiation
pneumonitis was not observed at average ILBs ≤0.63 kBq/kg (Muggenburg et al. 2008). In the ITRI
dogs, radiation pneumonitis occurred at similar initial lung burdens whether the
dogs were exposed as
juveniles, young adults, or elderly adults (DOE 1988d, 1989, 1994b; Hahn et al. 1999; Muggenburg et al.
1999). Radiation pneumonitis-induced death occurred earlier in the dogs exposed as elderly adults than in
the dogs exposed as young adults (DOE 1988d).
Exposure of Dogs to
239
Pu(NO
3
)
4
.
Radiation pneumonitis was the primary cause of death in all five dogs
that died early following exposure to
239
Pu(NO
3
)
4
aerosols at levels resulting in a mean
initial lung burden
of 18.83 kBq/kg; death was noted as early as 14-months postexposure (DOE 1988b; Park et al. 1995).
Data on the time to onset and clinical progression of disease or histopathologic findings were not
reported.
Exposure of Other Laboratory Animal Species.
Baboons that inhaled
239
PuO
2
displayed a pattern of
respiratory disease similar to that observed in dogs. Radiation pneumonitis-induced mortality was
observed in one baboon within 400 days following exposure to
239
PuO
2
that resulted in an estimated initial
lung burden of 28.5 kBq/kg body weight (Metivier et al. 1974, 1978b). Higher initial lung burdens
resulted in earlier death from radiation pneumonitis accompanied by pulmonary edema.
Radiation
pneumonitis and pulmonary fibrosis were also reported in Rhesus monkeys at initial lung burdens of
14.8 or 26.64 kBq/kg (LaBauve et al. 1980). Dose-related increased severity of radiation pneumonitis
and pulmonary interstitial fibrosis were observed in Cynomolgus monkeys exposed to
239
Pu(NO
3
)
4
at
levels resulting in initial total lung burdens ≥4.8 kBq/kg (based on reported initial lung burdens and mean
body weight) (Brooks et al. 1992). Monkeys with the highest initial lung burdens exhibited extensive
alveolar septal fibrosis and zonal pleural fibrosis accompanied by lymphocytic infiltrates and epithelial
hyperplasia of alveolar lining cells. Radiation pneumonitis and pulmonary fibrosis have also been
46
PLUTONIUM
3. HEALTH EFFECTS
observed in rats, mice, and hamsters that inhaled
239
PuO
2
(DOE 1986d; Lundgren et al. 1983, 1987, 1995;
Oghiso et al. 1994b; Sanders 1977; Sanders and Mahaffey 1979).
The highest NOAEL values and all reliable LOAEL values for respiratory effects in
dogs and nonhuman
primates exposed to aerosols of plutonium are recorded in Table 3-3 and plotted in Figure 3-1.
Cardiovascular Effects.
Epidemiological Studies in Humans.
Possible associations between exposure to plutonium and
cardiovascular disease have been examined in studies of workers at production and/or processing
facilities in the United Kingdom (Sellafield) (McGeoghegan et al. 2003; Omar et al. 1999). These studies
are summarized in Table 3-2 and study outcomes for mortality from cardiovascular disease are described
in Section 3.2.1.1. Omar et al. (1999) compared mortality rates between plutonium workers and other
radiation workers within a cohort of Sellafield workers and found that the mortality rate ratios were
significantly elevated for cerebrovascular disease (1.27, p<0.05) in a cohort of Sellafield workers. The
cumulative internal uptakes of plutonium in the cohort were estimated to range from 0 to 12 kBq, with
approximately 75% of the cohort having cumulative uptakes ≤250 Bq. McGeoghegan et al. (2003)
compared mortality rates between plutonium workers and other radiation workers within a cohort of
Sellafield workers and found that morality rate ratios for plutonium workers
were significantly elevated
for deaths from circulatory disease (2.18, p<0.05) and ischemic heart disease (4.46, p<0.01).
Studies in Animals.
No significant changes in cardiovascular function were seen in the ITRI dogs
exposed to
239
PuO
2
at initial lung burdens up to and including those resulting in radiation pneumonitis;
observed right ventricular hypertrophy was most likely a compensatory response to decreased respiratory
function (Diel et al. 1992; Muggenburg et al. 1999).
Gastrointestinal Effects.
Possible associations between exposure to plutonium and mortality from
diseases of the gastrointestinal tract have been examined in studies of workers at plutonium production
and/or processing facilities in the United Kingdom (Sellafield) (McGeoghegan et al. 2003; Omar et al.
1999). These studies are summarized in Table 3-2 and study outcomes for mortality are described in
Section 3.2.1.1.
Collectively, these studies have not found statistically significant associations between
mortality rates from diseases of the digestive tract and exposure to plutonium among workers at these
facilities.