Page 106 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Chemicals of Terrorism Chapter | 5 73

VetBooks.ir agonists can help if bronchospasm develops (Guloglu Mechanism of Action
et al., 2002).
Phosgene is a lower-respiratory-tract irritant. Due to its
Flush eyes with copious amounts of room temperature
0.9% saline or water for at least 15 min. Fluorescein low water solubility and low irritancy of the upper respi-
ratory system, phosgene is able to penetrate deeply into
staining should be performed to check for corneal defects
the lungs (Franch and Hatch, 1986). Phosgene gas inter-
(Grant and Schuman, 1993). Animals should be bathed
acts with water in the lungs, where it is hydrolyzed into
with copious amounts of soap and water. Chlorine blood
hydrochloric acid leading to cellular injury (Murdoch,
concentrations are not clinically useful as it converts
1993). Phosgene also acylates sulfhydryl, amine, and
directly to hydrochloric acid in the lungs and other
hydroxyl groups (Borak and Diller, 2001). This results in
tissues.
protein and lipid denaturation, changes in membrane struc-
Animal models have suggested that corticosteroids can
ture and disruption of enzymes. Phosgene increases pul-
hasten recovery from severe chlorine gas poisoning
monary vascular permeability, leading to increased fluid
(Traub et al., 2002); however, administration of steroids
accumulation in the lung interstitium and alveolae. This
to exposed humans has not been shown to provide any
fluid accumulation results in gas diffusion abnormalities
significant change (Chester et al., 1977). Pigs exposed to
and pulmonary edema (Diller, 1985). Phosgene also
chlorine gas responded best to a combination of aerosol-
decreases energy metabolism and disrupts the glutathione
ized terbutaline and budesonide than to either therapy
redox cycle. Animals exposed to phosgene have elevated
alone (Wang et al., 2004). Sheep exposed to chlorine gas
levels of leukotrienes and neutrophil chemotactic agents.
and then nebulized with 4% sodium bicarbonate had
Neutrophils congregate in the lung releasing cytokines and
decreased mortality and improved arterial blood gas
other reactive mediators that contribute to pulmonary
values (Chisholm et al., 1989). Other suggested therapies
injury (Sciuto et al., 1995). Bronchiolar epithelium is dam-
include IV sodium nitrite to replace NO and reduce
aged, resulting in local emphysema and partial atelectasis.
inflammation (Honavar et al., 2017) and melatonin as a
Death is due to anoxia secondary to pulmonary edema.
free radical scavenger (Pita et al., 2013).
Concluding Remarks Toxicity
Rescuers should wear self-contained breathing apparatus Most exposures to phosgene are from inhalation. The
and have protective clothing when entering contaminated odor of phosgene gas is not sufficient to warn individuals
areas. Chlorine dissipates quickly in warm climates and of toxic levels and with high concentrations; olfactory
does not leave an environmental residue (Munro et al., fatigue can occur (Borak and Diller, 2001; ACGIH,
1999). The potential for secondary contamination is low, 2005). The degree of pulmonary injury relates to the con-
as the gas is not carried on contaminated clothing. centration and length of exposure (Bingham et al., 2001),
and initial symptoms are not considered to be a good indi-
cator of prognosis (Diller, 1985).
PHOSGENE Exposure to concentrations less than 3 ppm may not be
Background immediately accompanied by symptoms, but delayed effects
usually occur within 24 h of exposure. Concentrations as
Phosgene (Agent CG, carbonyl chloride, CCl 2 O) is classi- low as 3 5 ppm can cause immediate conjunctivitis, rhini-
fied as a choking agent. It is a colorless, noncombustible, tis, pharyngitis, bronchitis, lacrimation, blepharospasm, and
and highly toxic gas. At room temperature phosgene is upper respiratory tract irritation and extended (170 min)
easily liquefied (ACGIH, 2005; Proctor and Hughes, exposure was fatal (Diller, 1985; Wells, 1985; Proctor and
2004), and at high concentrations, the gas has an odor Hughes, 2004). A dose of 50 ppm for 5 min may cause
described as strong, suffocating, and pungent. Lower con- pulmonary edema and rapid death (Chemstar, 1996; Borak
centrations are described as smelling like green corn or and Diller, 2001; RTECS, 2006).
“haylike” (Raffle et al., 1994; Budavari, 2000). A lag time of 1 6 h before the onset of respiratory
distress and pulmonary edema is common with acute,
high-dose exposures (.50 ppm/min). Signs can be
Pharmacokinetics/Toxicokinetics
delayed for up to 24 (most common) or 72 h with expo-
Dyspnea develops 2 6 h postexposure in most patients sures to lower concentrations (Proctor and Hughes, 2004).
but may be delayed up to 15 h (Borak and Diller, 2001). Thoracic radiographs can show evidence of pulmonary
With high concentrations (.200 ppm), phosgene can edema within 1 2 h of high-dose exposure, 4 6 h after
cross the blood air barrier in the lung and cause hemoly- moderate exposure, and approximately 8 24 h after low-
sis and coagulopathies (Sciuto et al., 2001). dose exposure (Diller, 1985).