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Postmortem plutonium tissue distributions were also measured in healthy subjects receiving a single
intravenous injection of
237
Pu(IV) citrate (Newton et al. 1998; Warner et al. 1994). As much as 73% of
the injected
237
Pu dose was found in the liver at 7–230 days postinjection; approximately half of the liver
237
Pu concentration was achieved within the first 2 days postinjection (Newton et al. 1998). Early
gonadal uptake of
237
Pu in four healthy males was in excess of 0.05%; mean retention between 30 and
86 days postinjection was approximately 0.015% (Warner et al. 1994).
Distribution of plutonium following intravenous injection of plutonium has been
studied in nonhuman
primates, dogs, and rodents (e.g., Bair et al. 1973; Bruenger et al. 1991a; Durbin et al. 1972, 1997;
Guilmette et al. 1978; Polig 1989; Polig et al. 2000; USNRC 1992).
3.4.3
Metabolism
Plutonium metabolism in physiological systems consists, primarily, of hydrolytic reactions and formation
of complexes with protein and nonprotein ligands. Plutonium can exist in oxidation states III–VI in
solution; however, under most (if not all) physiological conditions, the predominant state is Pu(IV)
(Gorden et al. 2003). At neutral pH, Pu(IV) ion rapidly undergoes hydrolysis to monomeric and
insoluble
polymeric plutonium hydroxides (e.g., nPu[OH]
4
) (Taylor 1973). Pu(IV) forms complexes with a variety
of physiological proteins, including albumin, globulins (e.g., transferrin), ferritin, and various low
molecular weight proteins (Gorden et al. 2003; Lehmann et al. 1983; Stevens et al. 1968; Stover et al.
1968a; Taylor 1973). The dissociation constant of Pu(IV)-transferrin complex
has not been measured;
however, the complex appears to be less stable than Fe(III)-transferrin complex (K
d
≈
10
-22
M) (Aisen and
Listowsky 1980; Turner and Taylor 1968). As a result, binding of Fe(III) to transferrin can influence the
degree of binding of Pu(IV). Excess iron results in reduced binding of plutonium to transferrin (Turner
and Taylor 1968). Plutonium also forms complexes with nonprotein ligands, polycarboxylates (e.g.,
citrate, lactate). The stability constants for the mono- and di-citrate
complexes are approximately
10
15
and 10
30
M, respectively (Taylor 1973).
3.4.4
Elimination and Excretion
Kinetics of elimination of absorbed plutonium reflect relatively long retention times of plutonium in liver
(half-time >9 years) and skeleton (half-time >20 years; ICRP 1994a, 1996a, 2001) (Leggett 1985), the
dominant sites of accumulation of absorbed plutonium. Analyses of data on excretion and tissue burdens
of plutonium in humans have contributed to the development of mechanistic models of plutonium kinetics
(see Section 3.4.5). These models predict observed multi-phasic elimination
kinetics, reflecting the
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PLUTONIUM
3. HEALTH EFFECTS
variation in kinetics and relative sizes of the major tissue depots for plutonium, with the half-time for the
dominant kinetic process estimated to be 50–100 years (ICRP 1972, 1979, 1994a; Khokhryakov et al.
2002; Leggett 1985). This general pattern of multi-phasic elimination with a dominant slow phase would
be expected to apply to absorbed plutonium regardless of the route of exposure. However, with inhalation
exposure, additional processes influence the elimination kinetics, including physical transformation and
dissolution of particles deposited in the lung, which can provide a source of replenishment of plutonium
to blood and other tissues (see Section 3.4.1.1).
3.4.4.1 Inhalation Exposure
Following inhalation exposure to PuO
2
, plutonium is excreted in feces and urine (DOE 1991c;
Khokhryakov et al. 2004; Kurihara et al. 2002; Voelz et al. 1979). Excretion in feces peaks within 2–
5
days following exposure, reflecting bronchial and tracheal mucociliary transport of deposited plutonium
particles to the gastrointestinal tract (Kurihara et al. 2002); however, it persists for years after cessation of
exposure (DOE 1991c; Khokhryakov et al. 2004; Voelz et al. 1979). In observations made on retired
plutonium workers (n=19, ≥40 years following retirement), the median value for fecal:urine excretion
ratio was 0.57 (GSD: 1.12; mean=0.83±0.73 SD) (Khokhryakov et al. 2004). Observations made at
earlier times yielded higher ratios, indicating a gradual decline in the ratio with time.
Group mean
fecal:urine ratios in 345 workers (2–30 years postexposure) ranged from approximately 0.7 to 1.4 and
were similar for oxides and nitrates (Khokhryakov et al. 2004). Voelz et al. (1979) determined a median
fecal:urine ratio of 0.30 for 12 former workers in the United States.
Kinetics of urinary excretion of inhaled plutonium reflect the kinetics of dissolution and absorption of
plutonium particles deposited in the lung (half-times 1–20 years) and the relatively long retention times of
plutonium in liver (half-time >9 years) and skeleton (half-time >20 years) (ICRP 1994a, 1996a).
Following inhalation exposure to
238
PuO
2
ceramic
particles, plutonium was not detected in urine until
123 days after exposure and peak excretion rates occurred approximately 1,000 days following exposure
(James et al. 2003). The delay in observed urinary excretion is thought to reflect, in part, the relatively
slow dissolution kinetics of the particles (half-time ≈7 years) (James et al. 2003). Over longer periods of
time following exposure, urinary excretion of plutonium exhibits multi-phasic kinetics, with declining
rates over time (Kathren and McInroy 1991; Suslova et al. 2006; Woodhouse and Shaw 1998).
Repeated
measurements of urinary plutonium excretion in 6 workers who experienced inhalation exposures to
aerosols of plutonium nitrate showed that excretion rate declined with a mean half-time of 12 years
(95% CI: 10–16 years), when measured at times 1,000–9,000 days postexposure (Woodhouse and Shaw