Uranium - Toxicology of Metals - page 875

Histological fi ndings include vesiculation (the forma-
tion of vesicles, or liquid fi lled sacs, causing swell-
ing), nuclear pyknosis (a reduction in the size of the
nucleus), and excessive vacuolation (void space). The
liver disturbances are seen clinically as congestion,
lesions, mild degeneration, and fatty infi ltration, with
urinary catalase being a biomarker of effect.
In one human case study, an individual who drank
uranyl acetate and benzodiazepine demonstrated liver
disfunction as increased serum levels of ALT, AST, and
GGK. These signs subsided 6 months after exposure
(Pavlakis et al ., 1996).
In animal inhalation studies, the impact on the liver
increased from no effect on rabbits exposed to 22 mgU/
m 3 as high-grade ore to focal necrosis of the liver for
rats exposed to 0.4 mgU/m 3 as uranium tetrafl uoride
(Dygert, 1949a,b). New Zealand rabbits exposed to
uranium as uranyl nitrate in drinking water (1.4 and
41 mg/kg/day) for 91 days showed irregular accentua-
tion of zonation in the liver, accompanied by increased
variation in hepatocellular nuclear size, nuclear pyk-
nosis, and extensive cytoplasmic vacuolization. These
changes were found to be treatment-related but not
dose-related (Gilman et al ., 1998).

thought to be a more sensitive species to the adverse
effects of uranium, and the apparent absence of effects
on brain histopathology of both the rat and rabbit.

7.1.6 Pulmonary Effects

The toxicity of inhaled uranium compounds on the
lung is a function of particle size and solubility. Higher
lung toxicity is associated with smaller particles (<5 m

are well retained) and lower solubility (dioxide, octaoxide,
and metal). The inhalation or ingestion of pure uranium
compounds has not been found to cause signifi cant harm
in human or animal studies unless it involved uranium
hexafl uoride or was injected. High-dose animal studies
did fi nd rhinitis and slight degenerative changes (in rats
and dogs exposed to 16 mg U/m 3 as uranium trioxide
and dogs exposed to 9.5 mg U/m 3 as uranyl nitrate, but
not when exposed to uranium dioxide and triuranium
octaoxide).
At extreme doses or when mixed with other toxic
agents (such as radon, silica, diesel particles, and other
fumes), the result can be interstitial infl ammation,
which for prolonged elevated exposure can lead to
pulmonary fi brosis, pulmonary edema, and eventu-
ally emphysema. A mixture of 1% U with 34% SiO 2 has
been found to induce tumor necrosis factor (TNF) and
the production of fi broblasts and collagen (Zhou et al.,
1999). These effects are comparable to those that have
been associated with inhaling diverse inorganic dust.
The 11th Report on carcinogens issued by the National
Institute of Environmental Health Sciences (NTP, 2005)
lists silica dust as a known human carcinogen and die-
sel particles as reasonably anticipated to be human car-
cinogens. This seems to be especially true for freshly
cracked silica dust present in mine air.

µ

7.1.5 Neurological Effects

Uranium does not seem to cause nervous system
problems in humans exposed by inhalation, ingestion,
or dermal contact. However, this may not be the case
for embedded fragments of uranium, such as in those
who received DU shrapnel wounds during the Persian
Gulf War. Some of these individuals have been followed
for more than a decade, and testing has indicated that
the uranium might cause a lowering of performance
effi ciency scores with electrophysiological changes in
the hippocampus. A follow-up study determined that
no statistically signifi cant differences existed between
low- and high-exposure groups for the neurocognitive
parameters measured. A potential decrease of accuracy
impairment index for the two most highly exposed
individuals may have been associated with complica-
tions of combat injuries (McDiarmid et al ., 2004).
Animals do not seem sensitive to uranium at low
doses, and results are equivocal at high doses. Rats fed
large doses of uranium had diffi culty walking, with
an unstable gait, weak muscles, and rigid limbs. Addi-
tional effects included piloerection, tremors, hypo-
thermia (lowered body temperature), decreased pupil
size, and exophthalmia (bulging of the eyeballs, com-
parable to that which occurs with hyperthyroidism).
In addition, they showed irritability, hyperactivity or
lassitude, and some respiratory arrest. Complicating
this picture are fi ndings that much larger doses did
not cause such effects in rabbits, which are generally

7.1.7 Renal Effects

Uranium can be toxic to the kidneys and is con-
sidered less potent than lead, cadmium, and mercury
(Goodman, 1985). Suffi ciently high doses irritate,
degenerate, or damage the kidney, with the most sensi-
tive portions being the proximal convoluted tubule fol-
lowed by the glomerulus. Low-dose irritation appears
as cell hyperplasia and metaplasia, which at higher
doses results in cellular necrosis. The shedded necrotic
cells are captured as hyaline casks that are found in
all portions of the tubular system. Glomerular dam-
age is revealed as a thickened glomerular capsular
wall, shrinkage of the glomerular capillary network,
and decreased glomerular fi ltration rates. This results
in increased urinary levels of amino acids, proteins,
glucose, alkaline phosphatase, and

β 2 -microglobulin
relative to creatinine, which are not specifi c to ura-
nium toxicity. If the dose is not lethal, regeneration of