Toxicological Profile for Plutonium

13 
PLUTONIUM 
2.  RELEVANCE TO PUBLIC HEALTH 
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.  The pattern of tumor development in dogs exposed to 
239
Pu(NO
3
)
4 
was similar to that of dogs exposed to 
238
PuO
2
, with tumors observed in lung, bone, and liver 
(principally of bile- duct epithelium).  Bone tumors were the main cause of death in the exposure groups 
with mean initial lung burdens of 1 and 5.9 kBq/kg.  In contrast to the high incidences of bone tumors in 
the dogs exposed to 
238
PuO
2
 or 
239
Pu(NO
3
)
4
 aerosols, cancer deaths in dogs exposed to aerosols of the 
relatively insoluble 
239
PuO
2
 were predominantly associated with lung tumors consisting mainly of 
papillary adenocarcinomas based on a lifespan composite study.  Tumor incidences at other sites in the 
239
PuO
2
-exposed dogs were not statistically significantly different from those of controls.  Earlier and 
shorter studies reported bronchiolo-alveolar carcinoma as the most frequently identified cancer type. 
Respiratory Effects. 
Possible associations between exposure to plutonium and respiratory tract 
disease have been examined in studies of workers at 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).  Collectively, these studies have not found significant associations between 
mortality rates from respiratory tract disease, other than cancer, and exposures to plutonium among 
workers at these facilities.  Possible associations between exposure to plutonium and pulmonary fibrosis 
were examined in a cohort of workers (n=326) at Rocky Flats.  The study assessed lung interstitial 
abnormalities from the most recent available x-rays in relation to estimated lung equivalent dose from 
plutonium.  Estimated lung equivalent doses ranged from 0 to 28 Sv (approximately 73% <1 Sv).  The 
odds ratio (adjusted for age, smoking status, and evidence from pleural abnormalities from possible 
asbestos exposure) was significant for the dose group 10 Sv (5.3, 95% CI:  1.2–23.4).  A report of one 
study was based on scoring radiographs for the severity of chest abnormalities considered consistent with 
fibrosis, and did not include information regarding a possible association between these lung 
abnormalities and clinical symptoms of disease.   
Radiation pneumonitis has been observed following inhalation exposure of dogs, nonhuman primates 
(monkeys and baboons), and rodents to plutonium (primarily insoluble) compounds, and was identified as 
primary, major contributing, or incidental cause of death in some dogs and nonhuman primates that 
inhaled 
238
PuO
2
, 
239
PuO
2
, or 
239
Pu(NO
3
).  Results of lifetime studies in dogs indicate that radiation 
pneumonitis in the 
239
PuO
2
-exposed dogs occurred at lower ILBs and had a shorter time to onset 
compared to 
238
PuO
2
- or 
239
Pu(NO
3
)
4
-exposed dogs.  This observation is consistent with the toxicokinetic 
differences observed for inhaled plutonium compounds, showing that inhaled 
239
PuO
2 
is cleared from the 

---

14 
PLUTONIUM 
2.  RELEVANCE TO PUBLIC HEALTH 
lung more slowly than 
238
PuO
2 
and 
239
Pu(NO
3
)
4
.  The radiation pneumonitis/pulmonary fibrosis 
progressively impaired lung function, including alveolar-capillary gas exchange, resulting in increases in 
respiratory rate, minute volume, arterial CO
2 
pressure, and lung stiffness, along with decreases in tidal 
volume and arterial O
2 
pressure.  Increases in radiation dose and dose rate corresponded to reduced times 
to the onset of symptoms and increased severity of effects.  Radiation pneumonitis tended to be observed 
at lower ILBs in the 0.75 and 1.5 µm AMAD groups than in the 3.0 µm AMAD group. 
Hematological Effects. 
Possible associations between exposure to plutonium and mortality from 
hematopoietic diseases have been examined in studies of workers at plutonium production and/or 
processing facilities in the United States (Rocky Flats), United Kingdom (Sellafield).  Collectively, these 
studies have not found significant associations between mortality rates from diseases of blood or blood-
forming organs and exposures to plutonium among workers at these facilities. 
Compound- and dose-dependent decreased numbers of selected white blood cells were observed in dogs 
exposed to plutonium aerosols.  Primary hematological effects following pulmonary deposition of 
238
PuO
2 
and 
239
Pu(NO
3
)
4 
were lymphopenia and neutropenia, whereas lymphopenia was both the first biological 
effect to be observed and the primary hematological effect of inhaled 
239
PuO
2
.  Persistent hematological 
effects occurred in 
238
PuO
2
- and 
239
PuO
2
-exposed dogs with initial lung burdens as low as 0.28 kBq/kg 
initial lung burdens that elicited hematological effects in 
239
Pu(NO
3
)
4
-exposed dogs appeared to be 
somewhat higher (mean initial lung burdens ≥5.91 kBq/kg.  For 
239
PuO
2
-exposed dogs, the time of onset 
for significant lymphopenia was inversely related to dose (112 days, 180 days, 1 year, or up to 5 years for 
ILBs of 29, 14, 6.4, and 3.7 kBq/kg lung, respectively).  Decreased lifespan was observed, although some 
of these dogs exhibited a return to normal lymphocyte counts after 5 years.  No changes in red blood cell 
counts were observed through year 7 other than a compensatory increase in animals with pneumonitis or 
pulmonary fibrosis.  Plutonium accumulated in the lymph nodes of the 
239
PuO
2
-exposed dogs, resulting in 
lymphoid atrophy and fibrosis, especially in the trachiobronchial region.  The lymphopenia was 
considered to be the result of lymphocytes being irradiated as they passed through pulmonary lymph 
nodes. 
Hepatic Effects. 
Possible associations between exposure to plutonium and mortality from liver 
disease (e.g., liver cancer) have been examined in studies of workers at 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).  Collectively, these studies have not found significant associations 

---