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PLUTONIUM
3. HEALTH EFFECTS
postexposure period represents a translocation rate of approximately 0.32% per year.
Redistribution of
plutonium from other soft tissue is expected to contribute to increased skeletal content over time as well.
Considerable effort and progress has been made in developing models that simulate the distribution and
elimination kinetics of absorbed plutonium. These models are described in greater detail in Section 3.4.5.
Organ Distribution of Absorbed Plutonium in Animals
. Numerous studies conducted in various animal
models, including nonhuman primates, rodents,
and dogs, provide additional evidence for distribution of
absorbed plutonium to thoracic lymph nodes, liver, and skeleton, following inhalation exposures to
plutonium aerosols (Bair et al. 1962b, 1966; Buldakov et al. 1972; Dagle et al. 1986; Guilmette et al.
1984; Lataillade et al. 1995; Mewhinney and Diel 1983; Morin et al. 1972; Muggenburg et al. 2008;
Nenot et al. 1972; Park et al. 1972; Sanders 1973; Sanders and Mahaffey 1979; Sanders et al. 1977).
These observations are consistent with the larger body of observations of the distribution of plutonium
following parenteral administration of plutonium compounds (Bair et al. 1973; DOE 1989; Vaughan et al.
1973).
Studies conducted in animals have also shown that particle size and physical and chemical form of
inhaled plutonium influence both the kinetics and patterns of tissue distribution of plutonium.
Muggenburg et al. (2008) showed that, for monodisperse particles of 0.75, 1.5, or 3.0 µm AMAD, the
smallest particles were most rapidly removed from the lungs during the first few hundred days.
Thereafter, removal of the larger particles was more rapid than that of the smaller particles; this trend
persisted past 6,000 days. The rate of particle distribution from the lung was greatest to the skeleton
followed by liver and spleen. Activity (as percent ILB) in the skeleton increased to 1% at 6,000 days.
Activity in the liver reached 10% at 1,500 days and slowly decreased thereafter. Activity in the spleen
reached 0.2% at 1500 days and likewise slowly decreased afterward. Activity in the kidney initially
reached 0.002% and then slowly decreased. In general, exposures to more insoluble forms of Pu (e.g.,
PuO
2
) result in distribution (percent of ILB) of plutonium from the lungs to thoracic lymph nodes
comparable to that of the liver and greater compared to that of more soluble Pu(IV) complexes (e.g.,
citrate, nitrate) (Bair et al. 1966, 1973; DOE 1988b, 1989; Morin et al. 1972; Muggenburg et al. 2008;
Park et al. 1972). The highest concentrations of plutonium in lymph nodes were observed initially in
thoracic lymph nodes. Levels in selected lymph nodes increased to 10% ILB after 500 days (thoracic
lymph nodes), 10% ILB at 6,000 days (mediastinal lymph nodes), 1% ILB at 2,000 days (hepatic lymph
nodes), 0.1% ILB at 6,000 days (sternal lymph nodes), and 0.01% ILB at 300 days (retropharyngeal
lymph nodes) (Muggenburg et al. 2008). Whereas plutonium concentrations in
the thoracic lymph nodes
of
239
PuO
2
-exposed dogs remain high during lifetime observation, Mewhinney and Diel (1983)
81
PLUTONIUM
3. HEALTH EFFECTS
demonstrated that the concentrations in the thoracic lymph nodes of
238
PuO
2
-exposed dogs rapidly
increased to peak levels (approximately 10% of the initial lung burden) within the first year postexposure,
then
declined to <5% of the initial lung burden during the next 3 years. This difference in retention of
plutonium by the thoracic lymph nodes is thought to result from radiation fragmentation and subsequent
dissolution of the resulting smaller
238
Pu particles, lymphatic transport to
systemic circulation, and
subsequent deposition principally in liver and skeleton (Mewhinney and Diel 1983). The method used to
produce PuO
2
also appears to affect the distribution of inhaled plutonium oxide. Distribution to thoracic
lymph nodes, bone, and liver was greater when exposure was to chemically prepared oxides or to air-
oxidized or low-fired plutonium compared to the high-fired forms (Bair et al. 1973; Sanders and
Mahaffey 1979).
Distribution of PuO
2
from the respiratory tract and associated lymph nodes is affected by the size of the
particles initially deposited in the lung. Larger particle sizes (e.g., 2–4 μm MMD) deposited in the
alveolar region of the lung undergo less extensive mucociliary transport to the gastrointestinal
tract and
more extensive transfer into bronchial lymph nodes (Bair et al. 1962b, 1973; Guilmette et al. 1984). On
the other hand, transfer to extra-respiratory tissues is augmented with decreasing particle size (e.g., <2 μm
mass median diameter [MMD]) (Bair et al. 1973; DOE 1989). Plutonium deposited in lung from
exposure to
238
PuO
2
or
239
Pu(NO
3
)
4
is rapidly and more extensively distributed to extra-respiratory tissues
than is
239
PuO
2
(Dagle et al. 1983, 1996; Guilmette et al. 1984; Park et al. 1997). For example,
1,000 days after beagles were exposed to aerosols of similarly sized particles of
238
PuO
2
or
239
PuO
2
, liver
and skeletal burdens (fraction of initial lung burden) were approximately 100
times higher in dogs
exposed to
238
PuO
2
, and lung burdens were approximately 3–5 times higher in dogs exposed to
239
PuO
2
(Guilmette et al. 1984; Park et al. 1997). The isotope effect is thought to result from the relatively high
specific activity of
238
Pu, which contributes to radiolytic fragmentation of Pu-containing particles in lung
and lymph nodes, augmenting transport and distribution to lymph and blood (Bair et al. 1973; Diel and
Mewhinney 1983). The distribution kinetics of inhaled
239
Pu(NO
3
)
4
more
closely resemble those of
238
PuO
2
than
239
PuO
2
(Dagle et al. 1983, 1996; Park et al. 1995).
Distribution of inhaled
239
PuO
2
to bone is influenced by age. In immature dogs, a 5-fold increase in
distribution to the bone was seen compared to that in young adult dogs (DOE 1986c). These
observations
are consistent with similar observations made following parenteral administration of Pu(IV) (Bruenger et
al. 1991a) and reflect higher bone turn-over in juveniles (see
Distribution within Bone).