Page 114 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Chemicals of Terrorism Chapter | 5 81

VetBooks.ir thiocyanate (Hall and Rumack, 1986). This reaction com- TABLE 5.4 LD 50 for Hydrogen Cyanide
Cyanide is metabolized by rhodanase in the liver to
plexes cyanide with endogenous sulfur or sulfur supplied
from the sodium thiosulfate antidote. Once thiocyanate is Species Route LD 50 (μg/kg)
formed it is excreted mainly in the urine. Half-life for the Mouse IM 2700
metabolism of cyanide to thiocyanate is 20 min to 1 h IP 2990
(Feldstein and Klendshoj, 1954). In animals, the dose of
Oral 3700
cyanide that produces signs is very close to the lethal
dose and death can occur within seconds to minutes. Rat SQ 3700
Source: Data from ACGIH, 2005. Threshold Limit Values (TLVs(R)) for
Chemical Substances and Physical Agents and Biological Exposure
Mechanism of Action Indices (BEIs(R)). American Conference of Governmental Industrial
Hygienists, Cincinnati, OH; Bingham, E., Chorssen, B., Powell, C.H., 5th
Cyanide causes its toxicity by forming a stable complex edn., 2001. Patty’s Toxicology, vol. 3. John Wiley & Sons, New York,
NY; Budavari, S., 2000. The Merck Index, 12th edn. on CD-ROM.
31
with ferric iron (Fe ) in cytochrome oxidase enzymes. Version 12:3a. Chapman & Hall/CRCnetBASE, Whitehouse Station, NJ;
Since oxygen is unable to reoxidize the reduced cyto- HSDB, 2005. Hazardous Substances Data Bank. (Edition expires in
2005.) National Library of Medicine, Bethesda, MD (Internet Version).
chrome a3, this inhibits cellular respiration, oxygen utili- Thomson MICROMEDEX, Greenwood Village, CO; Lewis, R.J., 2000.
zation and ATP production, resulting in deprivation of Sax’s dangerous properties of industrial materials, 10th edn. Van
Nostrand Reinhold Company, New York, NY; OHM/TADS, 2005. Oil
oxygen to the body at the cellular level (Way et al., and Hazardous Materials Technical Assistance Data System. U.S.
1988). In the brain cyanide decreases oxidative metabo- Environmental Protection Agency. Washington, DC (CD Rom Version).
Edition expires 2005; provided by Thomson MICROMEDEX, Greenwood
lism, increases glycolysis and inhibits brain glutamic acid Village, CO; RTECS, 2006. Registry of Toxic Effects of Chemical
decarboxylase, thereby decreasing GABA (Bingham Substances. National Institute for Occupational Safety and Health.
Cincinnati, OH (CD Rom Version). Edition expires 2006; provided by
et al., 2001). The corpus callosum, hippocampus, corpora Thomson MICROMEDEX, Greenwood Village, CO.
striata, and substantia nigra are commonly damaged in
cyanide poisoning (Grandas et al., 1989).
Early in cyanide toxicosis, CNS, respiratory, and myo- The blood, both arterial and venous, becomes cherry
cardial depression also contribute to decreased oxygen- red from accumulated oxyhemoglobin (Lewis, 2000;
ation of the blood and decreased cardiac output (Hall and Bingham et al., 2001). The skin may also be a bright pink
Rumack, 1986). There is also evidence of lipid peroxida- color from the high concentration of oxyhemoglobin in
tion by measurement of elevated levels of conjugated the venous return (HSDB, 2005). On funduscopic exam,
dienes in mouse brain and kidneys at 15 and 30 min after retinal arteries and veins will appear equally red. A
cyanide exposure (Ardelt et al., 1994). Cyanide salts are reduced arterio-central venous measured oxygen satura-
irritating upon ingestion and can cause corrosion of the tion difference may be seen due to the same cellular
oral, esophageal, or gastric mucosa (HSDB, 2005). inability to extract oxygen. This arterialization of venous
blood gases occurs early in the process of cyanide poison-
Toxicity ing. Tachycardia and hypertension may be seen in the ini-
tial phases of cyanide poisoning followed by bradycardia
Signs following acute cyanide exposure include syncope, and hypotension in the late phases. Cyanide exposure can
or CNS stimulation, dizziness, dyspnea, seizures, paraly- produce death within minutes. See Table 5.4 for LD 50 sof
sis, apnea, and coma (Hall and Rumack, 1986). HCN by various routes.
Tachypnea and hyperpnea are followed rapidly by respira- Cyanide can be measured in blood. No symptoms are
tory depression. Signs of severe hypoxia without cyanosis expected at concentrations less than 0.2 mg/L, tachycardia
can suggest the diagnosis. Signs in birds are similar to can be seen at 0.5 1.0 mg/L, obtundation at 1.0 2.5 mg/
those in mammals. Chickens will pant, have rapid eye L, coma and respiratory depression at levels greater than
blinking, produce excess salivation, and experience leth- 2.5 mg/L and death with blood levels greater than 3 mg/L
argy (Wiemeyer et al., 1986). Mydriasis is common in (Graham et al., 1977). Turn-around time makes these
severe poisonings, and blindness may occur from measurements not clinically useful.
cyanide-induced damage to optic nerves and retina (Grant
and Schuman, 1993). Nausea, vomiting, and abdominal
pain may occur, especially after ingestion of cyanide salts Treatment
(Hall and Rumack, 1986). Metabolic acidosis and lactic
acidosis are frequent metabolic derrangements. Blood Move animals to fresh air. Emesis is not recommended
gases show a decreased arterial venous oxygen satura- due to the rapid progression of the clinical signs and
tion difference due to the cellular inability to extract oxy- potential for seizures, coma or apnea. Activated charcoal
gen (Graham et al., 1977). may be beneficial if administered immediately after