47
PLUTONIUM
3. HEALTH EFFECTS
No reports were located regarding gastrointestinal effects in animals exposed to plutonium aerosols.
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) (Wiggs et al. 1994) and 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 blood or blood-
forming organs and exposure to plutonium among workers at these facilities.
Studies in Animals.
Inhalation exposure of dogs to plutonium compounds produced adverse
hematological effects, specifically decreased numbers of lymphocytes, neutrophils, and leukocytes.
Primary hematological effects of inhaled
238
PuO
2
and
239
Pu(NO
3
)
4
were lymphopenia and neutropenia. In
contrast, lymphopenia was the only hematological effect of inhaled
239
PuO
2
. The lymphopenia was
considered the result of lymphocytes being irradiated as they passed
through plutonium-containing
pulmonary lymph nodes. Effects were not observed on other blood cell types, perhaps the result of the
small fraction of
239
PuO
2
that translocated to bone or bone marrow (Muggenburg et al. 2008). No fatal
cancers of the hematopoietic system were reported in studies of dogs or monkeys exposed to plutonium.
Effects of plutonium compounds on functions of circulating immunological cells are discussed in
Section 3.2.1.2, Immunological and Lymphoreticular Effects
.
Exposure of Dogs to
238
PuO
2
. Lymphopenia and neutropenia were observed
in dogs exposed to
238
PuO
2
.
In the ITRI dogs, dose-dependent decreases in lymphocyte and neutrophil counts occurred during the first
year following exposure at initial lung burdens equal to 1 kBq/kg (Muggenburg et al. 1996). Similar
results were observed in the PNL dogs, although decreased lymphocyte counts were observed at a lower
initial lung burden (≥0.28 kBq/kg) than decreased neutrophil counts (≥4.68 kBq/kg) (Park et al. 1997).
Exposure of Dogs to
239
PuO
2
. Lymphopenia was both the first biological effect to
be observed and the
primary hematological effect observed in dogs exposed to
239
PuO
2
, although leukopenia, and transient
neutropenia have also been reported. Chronic lymphopenia developed during the first year of exposure in
the ITRI dogs with initial lung burdens ≥3.7 kBq/kg (Muggenburg et al. 1999, 2008). In the PNL dogs,
transient lymphopenia occurred at initial lung burdens ≥0.064 kBq/kg and transient and persistent
lymphopenia was noted at initial lung burdens ≥0.25 kBq/kg (Weller et al. 1995b).
The time of
occurrence for significant lymphopenia was inversely related to dose (112 days, 180 days, 1 year, or up to
48
PLUTONIUM
3. HEALTH EFFECTS
5 years for respective average initial lung burdens of 29, 14, 6.4, and 3.7 kBq/kg). Although the
lymphocyte counts returned to normal after 5 years for some of these animals, all experienced a
shortening of life. No changes in red blood cell counts were observed through year 7 other than a
compensatory increase in animals with pneumonitis or pulmonary fibrosis. In addition to lymphopenia,
plutonium accumulated in the pulmonary lymph
nodes of the
239
PuO
2
-exposed dogs. This resulted
initially in corticomedullary lymphoid atrophy and fibrosis in the hilar areas, especially in the
trachiobronchial region, and progressed to relatively complete atrophy and focal scarring (Muggenburg et
al. 2008). Repeated inhalation exposure to
239
PuO
2
produced lymphopenia in dogs with total lung burden
of 5.3 kBq/kg (Diel et al. 1992).
Other hematological effects observed in dogs exposed to
239
PuO
2
aerosols include transient neutropenia,
leukopenia, and erythrocytosis. Transient neutropenia developed 4 months after exposure to
239
PuO
2
in
the ITRI dogs with initial lung burdens ≥8.4 kBq/kg, although the duration of the effect was not reported
(Weller et al. 1995b). A reduction in total leukocytes was also observed in the PNL dogs at the “higher”
(not otherwise specified) initial lung burden levels (Park et al. 1997). Erythrocytosis, secondary to
decreased diffusing capacity of the lungs due to
radiation pneumonitis, was reported in the
239
PuO
2
-
exposed ITRI dogs (Muggenburg et al. 1999, 2008). Erythrocyte counts in were not affected in the
239
PuO
2
-exposed PNL dogs (DOE 1988a).
Exposure of Dogs to
239
Pu(NO
3
).
In PNL dogs exposed to inhaled
239
Pu(NO
3
)
4
, hematological effects
were the first exposure-related effect observed. Lymphopenia, leukopenia,
and neutropenia occurred
4 weeks after exposures resulting in initial lung burdens ≥5.91 kBq/kg (DOE 1988b). Leukopenia was
characterized by decreased numbers of neutrophils, lymphocytes, monocytes, and eosinophils.
Exposure of Other Laboratory Animal Species.
Lymphopenia was noted in Rhesus monkeys exposed to
239
PuO
2
aerosols, but initial lung burdens resulting in this effect were not specified (LaBauve et al. 1980).
Total leukocyte count (in the absence of lymphopenia and neutropenia) was decreased in Cynomolgus
monkeys exposed to
239
Pu(NO
3
)
4
, but the initial lung burdens at which the effect was noted were not
specified (Brooks et al. 1992).
The highest NOAEL values and all reliable LOAEL values for hematological effects
in each species and
duration category are recorded in Table 3-3.