Chemistry Reference
In-Depth Information
Centers for Disease Control and Prevention reported
average urine concentrations for the U.S. population
by age, gender, and ethnicity as measured by ICP-MS.
At the 95th percentile, the average was 0.046
air, food, and water produces a body burden that does
not call for treatment. When overexposure occurs or is
expected, samples should be collected of the contami-
nated material, urine, feces, vomitus, secretions from
any wounds, and any other items that are indicated,
and analyzed. Internal monitoring should be used, if
available, to quantify the internalized uranium ini-
tially and during treatment to assess its effectiveness.
Care should be taken to eliminate external contamina-
tion on skin or clothing that could be internalized or
radiologically masquerade as a larger amount of inter-
nalized uranium.
The generally recommended treatment method is
to alkalinize the urine to reduce the chance of causing
permanent damage or necrosis of the kidney tubules.
Sodium bicarbonate is suitable, because it complexes
with uranium, mobilizes uranium from sensitive tis-
sues or depot storage locations (kidney, liver, and
bone), and facilitates its elimination (Cooper
et al
., 1982;
Fisher
et al
., 1991). This is addressed in the following
along with summaries for other substances previously
evaluated with mixed reviews.
The treatment protocol recommended by the Radi-
ation Emergency Assistance Center/Training Site
(REAC/TS) is to dissolve 2 ampules of sodium bicar-
bonate (44.3 milliequivalents [mEq] each; 7.5%) in
1000 cm
3
normal saline and administer intravenously
at 125 cm
3
/hour. The alternate protocol is to orally
administer two bicarbonate tablets every 4 hours until
the urine reaches an alkaline pH of 8-9. Treatment can
be continued as long as it is effective and medically
indicated. Nonspecifi c treatment methods (induced
emesis or pulmonary lavage within reasonable time
frames) can also be conducted with medical oversight.
The use of calcium DTPA should be avoided, because
it may increase bone deposition of uranium (REAC/
TS, 2002). Although
in vitro
studies indicate that DTPA
may also enhance the cytotoxicity of uranium to renal
tubular epithelial cells, an
in vivo
study on rats found
no nephrotoxicity for a therapeutic regimen of 30
g/L for
all individuals age 6 and older, with a male/female
ratio of 1.15, and Mexican American concentrations
over twice that of non-Hispanic blacks and whites.
When normalized to creatinine, the male-female dif-
ference disappeared, but the Mexican to non-Hispanic
ratio increased to 3 for males. The mean population
values for the last survey period were 0.007
µ
µ
gU/L or
0.008
gU/g creatinine, whereas the 95th percentile val-
ues useful for screening purposes were 0.046
µ
µ
gU/L or
0.040
gU/g creatinine (CDC, 2005). Urinalysis can be
supplemented by gamma spectroscopy analysis of the
whole body or chest area with a sodium iodide or, pref-
erably, a hyperpure germanium detector. The United
States Transuranium and Uranium Registries (USTUR)
(Russell
et al
., 1996) has demonstrated through autopsy
results of highly overexposed workers that uranium is
present years after exposure and concentrates prima-
rily in bone and lung tissue.
µ
8.2 Biomarkers Used to Characterize Effect
No biomarkers of effect specifi c to uranium have
been identifi ed, but uranium overexposure is known
to damage renal proximal tubules and reduce urine
fi ltration, whereas higher levels damage the liver (Pav-
lakis
et al.,
1996; Stokinger
et al
., 1953; Zhao and Zhao,
1990). The urine of an individual adversely affected by
uranium will show elevated concentrations of catalase,
protein, glucose,
β
2
-microglobulin relative to creati-
nine, amino acids, and probably other substances not
well studied. Assessing multiple parameters simulta-
neously is an approach for uniquely identifying ura-
nium damage (Zamora
et al
., 1998), but an appropriate
test array has not yet been developed.
The USTUR reported that autopsy results from a
double-blind histological evaluation showed that kid-
ney damage to a highly overexposed worker was com-
pletely repaired over time. The pathologists could not
distinguishable slides of his tubules from those of an
unexposed individual.
mol
Zn-DTPA per kg followed by the same dose of Ca-
DTPA (Houpert
et al
., 2003).
Studies on animals have identifi ed several chelat-
ing agents that can increase the elimination of inter-
nal uranium, but their limited effectiveness (<40%)
when tested separately and in combination may
marginalize their value in treating cases of uranium
poisoning. These include gallic acid, DTPA (diethyl-
amine tetraamine pentaacetic acid), EDHPA (ethylen-
ediamine-N,N'-bis[2-hydroxyphenylacetic acid]), and
Tiron
®
(sodium 4,5-dihydroxybenzene-1,3-disulpho-
nate). The linear molecule, 3,4,3-LIHOPO, may be more
effective than sodium bicarbonate at reducing organ
burden in the rat if injected immediately on uptake
µ
9 TREATMENT METHODS FOR REDUCING
TOXIC EFFECTS
The kidney is the critical organ for inhaled or
ingested uranium (ATSDR, 1999), and treatment has
focused on reducing the uranium concentration in that
organ, as well as in bone, because it represents a signif-
icant long-term storage depot. Uranium from typical
