Uranium - Toxicology of Metals - page 874

or lethal doses. Uranium is also less likely to cause
adverse cardiovascular, gastrointestinal, hematologi-
cal, musculoskeletal, or ocular effects. Cancer has not
been associated with uranium exposure. When expo-
sure occurs in a manner than can produce extreme local
concentrations, such as in studies where metal pieces
were implanted to simulate fragment wounds or in in
vitro assessments, additional effects, including cancer,
may be possible (Miller et al ., 2000; 2005). Such poten-
tial effects have not been apparent in soldiers with
embedded uranium fragments from wounds received
a decade earlier (McDiarmid et al ., 2004).

with murine hematopoietic cells, and later found an
elevated rate of myeloid leukemia compared with
unexposed mice as long as a suffi cient number of pel-
lets had been implanted.

7.1.2 Dermal Effects

Skin contact with uranium or its compounds has not
been found to cause an adverse effect in humans. This
may be the result of good tolerance or that humans
have not been exposed to high enough levels long
enough for an effect to be observed.
High-dose studies in the rabbit and rat that used
highly soluble uranium compounds placed in contact
with shaved skin for many days have demonstrated that
uranium can cause cells to swell and vacuoles to form, as
if the cell is trying to compartmentalize and isolate itself
from the excess uranium. Manifestations include skin
irritation and infl ammation, which can lead to damage
of hair follicles and sebaceous glands. Continued high-
level exposure can produce ulceration and necrosis, so
damage can be permanent. The potential exists for an
immune system response leading to future contact der-
matitis, such as occurs with aluminum.
Uranyl nitrate applied to the shaved backs of rabbits
eventually caused moderate erythema (at 1.4 mgU/kg),
ulceration (at 4.2 mgU/kg), or superfi cial necrosis (at
56 mgU/kg). Such effects were not observed at much
higher doses for uranium octaoxide (147 mgU/kg), ura-
nium dioxide (458 mgU/kg), uranyl fl uoride (618 mgU/
kg), uranium trioxide (666 mgU/kg), or uranyl acetate
(3,929 mgU/kg) (De Rey et al ., 1983; Orcutt, 1949).

7.1 Organ and Tissue Effects
7.1.1 Cancer

Human and animal studies have not drawn any asso-
ciation between uranium exposure by normal routes
and cancer of any type. The International Agency for
Research on Cancer (IARC), the U.S. Department of
Health and Human Services, and the National Toxicol-
ogy Program have not classifi ed uranium as to its car-
cinogenicity (ATSDR, 1999). IARC (2006), for example,
assigned it to Group 3, which means it is not classifi -
able as to carcinogenicity to humans. IARC assessed
implants of depleted uranium and concluded that
there is inadequate evidence for its carcinogenicity
(IARC, 1999).
Lung cancer in miners of various types (uranium,
silver, coal) has been attributed to other known or sus-
pected carcinogens (radon gas, diesel exhaust particles,
or freshly cracked silica dust). The National Academy
of Sciences has determined that the most likely can-
cer to occur after oral exposure to uranium is osteosar-
coma, but the report also concluded that exposure to
natural uranium may not have a measurable effect
(BEIR IV, 1988). This potential has been studied in vitro,
and it was found that soluble and insoluble DU com-
pounds caused human osteoblast cells to change to the
tumorigenic phenotype (Miller et al ., 2000). This infor-
mation is currently not transportable to an assessment
of cancer in organs of individuals. In an intramuscu-
lar implantation study designed to mimic battlefi eld
shrapnel wounds, pellets of DU and tantalum as a
control (2 × 1 mm cylinders, 2.5 ± 2.5 mm squares, and
5 × 5 mm squares) were implanted in the hindquarters
of rats. Tumor rates were determined at the end of
the lifespan. Implantation site sarcomas were signifi -
cantly increased in the large DU square group, slightly
increased in the large Ta and small DU groups, and
unaffected by the DU pellets, indicating the shape of
DU fragments is a factor in shape-related carcinogen-
esis (Hahn et al ., 2002). Miller et al . (2005) implanted
leukemia-prone mice with DU pellets, injected them

7.1.3 Developmental Effects

Humans have not shown any developmental effects
from uranium exposure at levels thus far received.
Animal results are negative except for high oral doses
(Domingo et al ., 1989; Paternain et al ., 1989). Then there
is a decrease in viability index (number of pups via-
ble at day 21/number born), lactation index (number
of pups viable at 21 days/number retained at day 4),
and growth. Those that survive longer can have skel-
etal malformations (bipartite sternebrae, reduced or
delayed ossifi cation at >14 mgU/kg/day), cleft pal-
ate, and renal underdevelopment. This shows the pro-
pensity of uranium to affect the kidney and deposit in
bone.

7.1.4 Hepatic Effects

The liver is probably an order of magnitude less sen-
sitive to damage than is the kidney, and many animal
studies are negative, even at high doses. When dam-
age does occur, it involves the disruption of cell func-
tion and permeability, but the etiology is not known.