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3.11 METHODS FOR REDUCING TOXIC EFFECTS
This section will describe clinical practice and research concerning methods for reducing toxic effects of
exposure to plutonium. However, because some of the treatments discussed may be experimental and
unproven, this section should not be used as a guide for treatment of exposures to plutonium. When
specific exposures have occurred, poison control centers and medical toxicologists should
be consulted
for medical advice. The following texts provide specific information about treatment following exposures
to plutonium:
Ellenhorn MJ, Schonwald S, Ordog G, et al., eds. 1997. Radiation poisoning. Ellenhorn's medical
toxicology. Diagnosis and treatment of human poisoning. Baltimore, MD: Williams & Wilkins, 1682-
1723.
REAC/TS. 2010a. Package insert-instructions for use: Pantetate calcium trisodium injection. Radiation
Emergency Assistance Center/Training Site. Oak Ridge Institute for Science and Education. U.S.
Department of Energy. http://orise.orau.gov/files/reacts/Calcium-DTPA-package-insert.pdf. May 22,
2010.
REAC/TS. 2010b. Package insert-instructions for use: Pantetate zinc trisodium injection. Radiation
Emergency Assistance Center/Training Site. Oak Ridge Institute for Science and Education. U.S.
Department of Energy. http://orise.orau.gov/files/reacts/Zinc-DTPA-package-insert.pdf. May 22, 2010.
Viccellio P, Bania T, Brent J, et al., eds. 1998. Ionizing radiation. Emergency toxicology. 2nd ed.
Philadelphia, PA: Lippincott-Raven Publishers, 991-996.
Wang RY, Chiang WK. 1998. Radiation poisoning. In: Haddad LM, Shannon MW, Winchester JF,
eds. Clinical management of poisoning and drug overdose. 3rd ed.
Philadelphia, PA: W.B. Sanders
Company, 413-425.
Compounds used to reduce absorption and body burden are used for heavy metals in general. However,
treatment procedures have been adapted and used for the management of plutonium exposures in the
workplace. Treatments using chelators are well accepted. REAC/TS has tested and possesses the
investigational new drug license for the use of calcium and zinc diethylaminetriaminepentaacetic acid
(Ca-DTPA and ZN-DTPA) in the United States. These substances were tested on adults and
their safety
and effectiveness was established for the adult population. This was extrapolated to the pediatric
population based on comparability of pathophysiologic mechanisms (REAC/TS 2010a, 2010b).
Pulmonary lavage is a unique treatment for reducing the lung burden from inhaled insoluble plutonium
compounds. It has been used only occasionally and is useful only in cases involving relatively high lung
burdens of insoluble plutonium compounds.
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3.11.1 Reducing Peak Absorption Following Exposure
Topical applications of DTPA solution have been used to remove plutonium from skin and wounds after
accidental dermal exposure (Khokhryakov et al. 2003).
In extracellular fluid, the chelating agent, DTPA
(a polycarboxylate compound), forms stable water-soluble complexes, which can be excreted in the urine
(Durbin 1973; Taylor 1973). Both Ca-DTPA and Zn-DTPA complexes are
used to decrease the risk of
calcium and zinc depletion. Based on animal experiments, it appears that administered DTPA aerosols
would form stable complexes with soluble forms of inhaled plutonium in the lung, thus reducing the
amount of plutonium available for systemic deposition following absorption (Gervelas et al. 2007;
Ménétrier et al. 2005; Sérandour et al. 2007; Stradling et al. 2000b). Bronchopulmonary lavage has been
recommended in cases where inhalation of insoluble plutonium compounds such as
239
PuO
2
may result in
doses to the lung in excess of 5 mSv within a few weeks (CEC/DOE 1992; Wood et al. 2000).
Postexposure treatments that are effective in reducing toxic effects of radionuclides
such as plutonium
typically concentrate on decorporation (removal of plutonium from the body following absorption) and
are discussed in Section 3.11.2.
3.11.2 Reducing Body Burden
Numerous animal studies have been performed to assess the effectiveness of various methods for
decorporation of absorbed plutonium and other radionuclides. Recent summaries of results from animal
studies and published guidance for decorporation of radionuclides such as plutonium include CEC/DOE
(1992); Gorden et al. (2003); Ménétrier et al. (2005); Stradling et al. (2000a, 2000b); and Wood et al.
(2000).
DTPA has been used as a chelating agent to accelerate the urinary excretion of plutonium in humans who
were accidentally exposed to plutonium. In one case of accidental exposure to
plutonium nitrate,
absorption into the blood from a skin wound reached 4.3% of the amount deposited on the skin; as a
result of prompt and repeated intravenous injections of DTPA, most of the absorbed plutonium was
excreted in the urine (Khokhryakov et al. 2003). Recent recommendations suggest using the Ca-DTPA
complex for initial treatment and the Zn-DTPA complex for subsequent administrations (Ménétrier et al.
2005), although Zn-DTPA has not been universally authorized for use.
Prolonged use of Ca-DTPA
results in the depletion of essential metals (particularly zinc), whereas gram quantities of Zn-DTPA can
be administered indefinitely without such depletion. With the exception of
the liver, DTPA appears to
form complexes primarily with plutonium in soft tissues other than the liver, which exchanges more