Uranium - Toxicology of Metals - page 869

that age has little effect on absorption (Leggett and
Harrison, 1995; Limson-Zamora et al ., 1992), but ani-
mal studies are not supportive on this point.
Animals absorb comparable percentages of ingested
uranium, with a central value of 1%. A 2-year feeding
study in rats found factors of 0.05-0.5% for uranyl fl u-
oride and 0.5-2% for uranyl nitrate, with a rate that
was independent of uranium concentration (Wrenn
et al ., 1985). The rates in rats were increased a factor of
2 by fasting (Sullivan et al., 1986), 3.4 by iron defi ciency
(Sullivan and Ruemmler, 1988), and 3.6 when neonates
were compared with adults (Sullivan, 1980b). Fasting
showed that these effects occur in mice and baboons
(Bhattacharyya et al ., 1989). Also, the fractional absorp-
tion for uranyl nitrate was found to be up to a factor of
3 higher in 2-day-old rats (1-7%) than for adults (Sul-
livan and Gorham, 1982), but comparable to that for
other animals (0.038-0.078 for rats; Wrenn et al ., 1995).

after 100 hours (Bassett et al ., 1948; Bernard and Struxness,
1957). There is an initial preferential concentration in
liver and kidney, but this shifts quickly to include bone.
The concentration in tracheobronchial lymph nodes
(for insoluble forms) and bone rise over time because
of limited turnover.
Bone eventually becomes the largest long-term repos-
itory of uranium for all exposure scenarios other than
heavy inhalation exposure in the workplace. Occupa-
tional inhalation exposure adds to the long-term lung
burden, increases the lung/bone ratio, and can cause
the lung to be the largest repository. ICRP (1996) con-
siders that the typical human body burden of uranium
from ambient exposure is 90

g, with 66% estimated to
be in the skeleton, 16% in the liver, 8% in the kidneys,
and 10% in other tissues (ICRP, 1996). Fisenne (1993)
ranked the organs as bone (57%) > muscle > fat > blood
> lungs > liver > kidney (0.36%). This is the same order
as found in a study of nonoccupational Asian adults in
China, India, Philippines, and the Republic of Korea.
The content of various organs (5.23

µ

5.1.3 Dermal Exposure

µ g in skeleton,

Dermal absorption has not been quantifi ed in
humans, but toxicity experiments in animals (mice,
rats, rabbits, and guinea pigs) indicate that water-solu-
ble uranium compounds are the most easily absorbed
through the skin and eye (Orcutt, 1949). Uranyl nitrate
applied to the skin penetrated the stratum corneum
within 15 minutes, accumulated initially in the skin,
and then distributed over the next 48 hours producing
renal effects. No penetration was observed for the more
insoluble dioxide, acetate, or ammonium diuranate
(De Rey et al ., 1983). Once systemic, the uranium can
distribute in the same manner as with oral exposure.

1.09 g in kidney)

was reportedly 40 times lower for the kidney and 10
times lower for the skeleton than would be predicted
by the ICRP Reference Man model. The skeletal burden
for the Asians was 4 times lower than for Chinese and
comparable to Indians, whereas the kidney burden was
comparable across the groups (Iyergar et al ., 2004). For a
long-term, highly exposed worker whose primary route
of exposure was inhalation and whose highest urinalysis
value was 30

µ g in lungs, 0.20 µ g in liver, and 0.19 µ

g/L, a full body autopsy at age 83 found
the highest uranium concentrations in tracheobronchial
lymph nodes and the rank order of organ content was
lung > skeleton > liver > kidney (Russell and Kathren,
2004). In a comprehensive study of tissues from two long-
time residents of an area with high well water concen-
trations who had no known occupational exposure, the
skeleton was the primary depot for uranium (Kathren,
1997). It is not known whether maternal bone stores of
uranium (like those of calcium and lead) are mobilized
during pregnancy and lactation.
Animal studies have shown similar relative distribu-
tions. Inhalation of the most soluble compounds showed
no long-term accumulation unless the dose was very
high (>0.25 mgU/m 3 ). When insoluble uranium dioxide
was inhaled for up to 5 years, accumulation did occur
(in the tracheobronchial lymph nodes, lungs, bones,
and kidneys of rats, dogs, and monkeys), but most
was cleared over a period of a few years after exposure
ended (Leach et al ., 1973). For ingested uranium in the
rat, doses >20 ppm (a mass fraction of 2 × 10 −5 ) caused a
rapid increase in organ content, indicating that this may
be a threshold for renal effects (Arruda-Neto et al ., 2004).
The distribution of uranium from metal implanted in

µ

5.2 Metabolism and Distribution
Uranium in body fl uids generally exists as a ura-
nyl ion UO 2 2+ complex. For tetravalent uranium, this
occurs by oxidation to the hexavalent form, and hexav-
alent uranium is converted to the uranyl ion. Metallic
uranium (e.g., as embedded fragments from military
wounds) dissolves slowly and is similarly converted.
The uranyl ion then generally complexes with citrate
or bicarbonate anions or with plasma proteins (Cooper
et al ., 1982; Dounce and Flagg, 1949; Stevens et al ., 1980).
For all routes of exposure, uranium distributes
through the blood throughout the body and is rapidly
taken up by the tissues or excreted in the urine. Fisenne
and Perry (1985) found whole blood and red cells of
New York City residents averaged 0.14 mgU/kg com-
pared with values ranging from <0.04-86 mgU/kg
globally. When uranium was intravenously injected
(as uranyl nitrate), 25% remained in the blood after
5 minutes, 5% after 5 hours, 1% after 20 hours, and <0.5%