Page 110 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Chemicals of Terrorism Chapter | 5 77

VetBooks.ir antibiotic should be started if leukopenia develops (Sidell Dermal absorption occurs within 3 5 min, especially fol-
et al., 1997). Antibiotic choice should be based on culture
lowing liquid exposures (Sidell et al., 1997). Lewisite has
extensive tissue distribution (HSDB, 2005). In rabbits, the
and sensitivity if possible.
Mustard can be detected in air, urine and body tissues liver, lungs and kidneys had the highest concentration of
using different methods. Mustard gas or its thiodiglycol arsenic after Lewisite administration (greater than seven
metabolite can be detected in urine up to a week after times blood concentration). Arsenic can cross the placenta
acute exposure using gas chromatography (GC)-mass and is passed into the milk, and nursing animals may be
spectrometry (Vycudilik, 1985). Other than for confirm- at risk (Barlow and Sullivan, 1982).
ing the diagnosis, measuring mustard gas levels is not Animal studies showed that excretion of Lewisite
likely to be of value in the management of the patient. oxidation products into the bile caused focal necrosis of
the liver and necrosis of biliary vessel mucosa with peri-
biliary hemorrhages (Munro et al., 1999). The same
Concluding Remarks
studyinrabbitsfoundthatarsenic was eliminated with a
Due to its low volatility, mustard is persistent in the envi- half-life in blood of 55 75 h (HSDB, 2005). The excre-
ronment. It persists for shorter periods of time in a hot cli- tion of oxidized Lewisite products into the bile by the
mate, but reaches higher vapor concentrations more liver may result in injury to the intestinal mucosa
rapidly. In temperate areas mustard may persist for more (Munro et al., 1999).
than 1 week, but in desert conditions, persistence is
reduced to about 1 day. Mustard will bind to vegetation Mechanism of Action
for days to weeks (USACHPPM, 2001b). Detection tubes
can be used to monitor airborne levels of mustard gas Besides being a vesicant, Lewisite is an arsenical com-
(IARC, 1975). pound that causes systemic effects. Lewisite directly
The potential for secondary contamination is high. effects enzyme systems. The exact mechanism of action
Rescue personnel must wear protective clothing, eye pro- is unknown, but it inhibits a variety of enzymes (pyruvic
tection and a respirator (HSDB, 2005). Mustard gas pene- oxidase, alcohol dehydrogenase, succinic oxidase,
trates wood, leather, rubber and paints. Medical personnel hexokinase, and succinic dehydrogenase) (DeRosa
treating mustard-exposed patients have developed toxicity. et al., 2002). Lewisite binds with thiol groups on these
enzymes, resulting in decreased ATP production.
Ocular injuries following Lewisite exposure are due in
LEWISITE
part to the liberation of hydrochloric acid. Deep pene-
Background tration of Lewisite into the cornea and aqueous humor
causes rapid necrosis (Goldfrank et al., 1998).
Lewisite (C 2 H 2 AsCl 3 ) is a substituted arsine. Lewisite Lewisite causes increased capillary permeability.
was first synthesized in 1918 by a research team headed Systemic absorption and increased permeability can cause a
by US Army Captain W.L. Lewis. It is an oily vesicant significant loss of blood plasma volume and is called
(blister-causing) liquid with potential terrorist use. “Lewisite shock” since it is similar to that of shock
Lewisite smells like geraniums. Pure Lewisite is colorless, observed in severe burns. The leakage of fluid into the
but impurities and age cause the color to darken (amber extravascular space results in hypotension (Sidell et al.,
to black or violet to brown, to olive-green) (HSDB, 1997). The exact mechanism of increased capillary perme-
2005). Lewisite remains a liquid at low temperatures and ability is not known. Theories include a capillary dilating
is persistent in colder climates. It hydrolyzes rapidly, material released from skin or tissue, or alternatively,
making it difficult to maintain a biologically active con- enhanced permeability from an interference with the metab-
centration on a humid day (Sidell et al., 1997; AAR, olism of capillary endothelial cells (Goldman and Dacre,
2000; Lewis, 2000; HSDB, 2005). Lewisite can be dis- 1989). Lung capillaries appear to be the most affected due
persed in air as a very fine droplet spray over a large dis- to absorption via the respiratory tract and first pass through
tance (Grant and Schuman, 1993; Lewis, 2000). the lungs following dermal exposure. Pulmonary edema or
ARDS can develop (Sidell et al., 1997).
Pharmacokinetics/Toxicokinetics
Toxicity
Lewisite can cause systemic signs when ingested, inhaled
or when absorbed dermally or ocularly (Sidell et al., Due to its method of dispersal (bursting charge of explo-
1997; HSDB, 2005). Inhalation of vapor causes immedi- sive), the main routes of absorption are dermal and respi-
ate pain, and if high enough concentrations are inhaled, ratory. Lewisite first acts as a vesicant, then as a
death can be seen within 10 min (DeRosa et al., 2002). pulmonary irritant and finally as a systemic poison.