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122
3. HEALTH EFFECTS
Excretion.
Absorbed plutonium is excreted in urine and feces. Following inhalation
exposure to
plutonium aerosols, plutonium particulates are transported from the respiratory tract to the gastrointestinal
tract. Because the fractional absorption of plutonium in the gastrointestinal tract is approximately 1x10
-3
–
1x10
-4
, nearly all of this transported plutonium is excreted in feces. This mechanism explains the fecal
excretion that has been observed in humans and animals during the first few days following exposure.
Mechanisms for fecal excretion that persists for months to years following exposure are not as well
understood. Plutonium injected intravenously is excreted in feces in humans (Langham 1959; Talbot et
al. 1993, 1997), nonhuman primates (USNRC 1985), dogs (Bair et al. 1974; Ballou et al. 1972; Guilmette
and Muggenburg 1993; Stover et al. 1959), and rodents (Carritt et al. 1947).
Direct evidence for biliary
secretion of injected plutonium comes from studies conducted in rats (Ballou et al. 1972; Bhattacharyya et
al. 1978).
Mechanisms of urinary excretion have not been elucidated and may involve excretion of plutonium from
plasma, or secretion of plutonium into urine from renal tissue. In plasma, plutonium exists predominantly
bound to proteins; <5% appears to be in the form of low-molecular weight complexes. The dominant
protein complex is with transferrin (molecular weight=88 kDa), which can account for 90% of plasma
plutonium following intravenous administration of either Pu-citrate complex or Pu(NO
3
)
4
(Lehmann et al.
1983; Stevens et al. 1968; Stover et al. 1968a; Taylor 1973). Renal clearance (plasma-to-urine) of
transferrin in humans is approximately 1-3x10
-4
L/day (Pesce and First 1979); this corresponds to a
plasma half-time of approximately 20–40 years (assuming a plasma volume in the adult human of 3 L).
Therefore, excretion of circulating Pu-transferrin complex is unlikely to account for blood-to-urine
clearances reported in adults (e.g., corresponding half-times 7–30 days) (Etherington et al. 2003; Leggett
1985). Other possible mechanisms that contribute to urinary excretion are blood-to-urine clearance of
low molecular weight plutonium complexes, or secretion of plutonium from tissue into urine.
3.5.2
Mechanisms of Toxicity
Toxicity of plutonium derives from the biological effects of radiation emitted
during the radiological
decay of plutonium isotopes. The isotopes
238
Pu and
239
Pu decay by emitting a high-energy alpha particle.
A very small amount of the energy in the form of gamma rays is also released during the decay of
plutonium isotopes. However,
gamma radiation from
238
Pu and
239
Pu decay is of such small magnitude
and energy that the dominant mechanisms of toxicity are associated with alpha radiation. Molecular
damage results from the direct ionization of atoms that are encountered by alpha (and gamma) radiation
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123
3. HEALTH EFFECTS
and by interactions of resulting free radicals (e.g., H
•
, OH
•
) with nearby macromolecules (e.g., lipids,
nucleic acids, proteins). Tissue damage results when the molecular damage is sufficiently extensive
and/or repair of the damage is not sufficiently rapid.
Alpha radiation emitted by plutonium isotopes cannot penetrate the outer layers of the skin. However,
once plutonium is internalized, the extremely short-range alpha radiation produces a very localized
radiation dose.
As a result, toxicity of plutonium coincides with the distribution of plutonium in the body.
As discussed in Section 3.4, Toxicokinetics, the distribution of plutonium depends on many factors,
including route of exposure, chemical form and physical characteristics of the plutonium compound (and
its complexes), and isotope specific activity (i.e., Bq/g). The patterns of toxicity observed in dogs
exposed to various compounds of plutonium reflect, primarily, the distribution
of plutonium that follows
exposure to each compound. Lung cancers and other effects of
239
PuO
2
on the lung (e.g., pneumonitis)
were the dominant effects observed in dogs following inhalation of
239
PuO
2
, which is cleared relatively
slowly from the lung (and from thoracic lymph nodes).
As a result, following inhalation exposures to
239
PuO
2
, the highest radiation doses (i.e., effective dose equivalents) occur in the lung. In contrast,
inhaled
238
PuO
2
is more rapidly cleared from the lung and, once absorbed, distributes primarily to skeletal
tissues (bone surfaces and marrow) and liver, resulting in relatively high radiation
doses to bone and liver,
as well as to lung. This is consistent with observations of bone, liver, and lung toxicity in dogs following
inhalation exposures to
238
PuO
2
.
Animal-to-Human Extrapolations
Mechanisms of toxicity and toxicokinetics of plutonium, described in Sections 3.5.1 and 3.5.2, are
directly applicable to humans. Numerous studies of the distribution of plutonium in humans (i.e., autopsy
studies of individuals occupationally exposed to plutonium) have shown that the general pattern of
distribution of plutonium in humans is consistent with that observed
in various animal models, with the
highest portion of the body burden in lung (following inhalation exposures), skeletal tissues, and liver.
Epidemiologic studies of health outcomes among workers in industries that produce and/or process
plutonium have provided evidence for increased risk of lung, liver, and bone cancers in association with
exposures to plutonium. These observations are consistent with the pattern of health effects observed in
animals.