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Related Articles | CBRNE - Cyanides, Cyanogen Chloride
CBRNE - Nerve Agents, Binary: GB2, VX2
CBRNE - Nerve Agents, G-series: Tabun, Sarin, Soman
CBRNE - Nerve Agents, V-series: Ve, Vg, Vm, Vx
Shock, Septic
Toxicity, Carbon Monoxide
Toxicity, Ethylene Glycol
Toxicity, Hydrogen Sulfide
Toxicity, Isoniazid
Toxicity, Organophosphate and Carbamate
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AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: Erik D Schraga, MD, Consulting Staff, Department of Emergency Medicine, Mills-Peninsula Emergency Medical Associates; Consulting Staff, Permanente Medical Group, Kaiser Permanente, Santa Clara Medical Center
Coauthor(s):
Andre Pennardt, MD, FACEP, FAAEM, Adjunct Assistant Professor of Military and Emergency Medicine, Uniformed Services University of the Health Sciences; Consulting Staff, Department of Emergency Medicine, Aviation Medicine and Dive Medicine, Womack Army Medical Center
Editors: Suzanne White, MD, Medical Director, Regional Poison Control Center at Children's Hospital, Program Director of Medical Toxicology, Associate Professor, Departments of Emergency Medicine and Pediatrics, Wayne State University School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Rick Kulkarni, MD, Medical Director, Assistant Professor of Surgery, Section of Emergency Medicine, Yale-New Haven Hospital; John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center; Robert G Darling, MD, FACEP, Clinical Assistant Professor of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Director, Center for Disaster and Humanitarian Assistance Medicine
Author and Editor Disclosure
Synonyms and related keywords:
cyanides, AC, hydrocyanic acid, HCN, cyanide, chemical warfare agent, chemical weapon, cyanide exposure, hydrogen cyanide exposure, cyanogen chloride, cyanide poisoning, hydrogen cyanide poisoning, hydrogen cyanide exposure, terrorism
Background
Hydrogen cyanide (HCN; North Atlantic Treaty Organization [NATO] designation AC) is 1 of 2 cyanide chemical warfare agents. The other is cyanogen chloride (NATO designation CK). Cyanide was first used as a chemical weapon in the form of gaseous HCN in World War I. The French used approximately 4000 tons without notable military success starting in 1915. This was most likely because of the high volatility of cyanide and the fact that the 1- to 2-lb munitions used could not deliver the amounts of chemical required for biological effects. The introduction of cyanogen chloride by the French in 1916 presented a more toxic compound with less volatility, improving its effectiveness as a chemical agent. Other alleged military uses of cyanide include Japanese attacks on China before and during World War II and Iraqi attacks on Kurds in the 1980s. Cyanide is a rapidly lethal agent when used in enclosed spaces where high concentrations can be achieved easily. In addition, because of the extensive use of cyanide in industry in the United States, this agent presents a credible threat for terrorist use. Emergency physicians may also encounter cyanide casualties resulting from industrial accidents. Specific industrial processes involving cyanide include metal cleaning, reclaiming, and/or hardening, fumigation, electroplating, and photoprocessing. Other potential sources of cyanide are fires involving plastics and/or synthetics, acrylic nail removers containing acetonitrile or propionitrile, or nitroprusside infusions. Numerous plants such as apricots, apples, and bitter almonds contain within their seeds and pits amygdalin, which can be hydrolyzed to AC following the ingestion of large quantities.
For related information, see Medscape's Disaster Preparedness and Aftermath Resource Center.
Pathophysiology
While liquid cyanide can be absorbed through the skin or eyes, the primary route of exposure is by inhalation or ingestion. Following absorption, cyanide is distributed rapidly to all organs and tissues in the body. Cyanide combines with ferric iron in cytochrome a3 (the last component of the cytochrome oxidase electron transport chain in mitochondria) and inhibits this enzyme. This prevents intracellular oxygen use and the generation of cellular ATP, ceasing aerobic energy production. Anaerobic production of ATP continues as pyruvate is converted to lactate. Metabolic acidosis ensues rapidly not due to lactic acidosis, but rather as a result of cells continuing to produce hydrogen ions through use of ATP without the balance of consumption by oxidative phosphorylation.
Frequency
United States
Emergency physicians are unlikely to encounter casualties from hydrogen cyanide used as a weapon except in the setting of a terrorist attack. Typical cyanide exposures are the result of liberation of the chemical during house and/or industrial fires or accidents.
Mortality/Morbidity
The LCt50 (concentration-time product capable of killing 50% of exposed group) for AC is 2500-5000 mg·min/m3. The lethal oral dose of AC and cyanide salts is estimated to be 50 mg and 100-200 mg, respectively. The LD50 (dose capable of killing 50% of exposed group) for skin exposures is estimated at 100 mg/kg. Vapor exposures in high concentrations (at or above the LCt50) typically can cause death in 6-8 minutes.
History
Key historic features for suspected hydrogen cyanide casualties include onset, severity, and time course of symptoms, time and nature of exposure, route of exposure, presence of smoke, odors and colors of gas, effects on surroundings (dead animals, other human casualties), and evidence of exposure to other chemicals or co-ingestants. As many as 50% of patients exposed to cyanide may describe an odor of bitter almonds.
- Symptoms after high vapor exposure
- Transient hyperpnea and hypertension 15 seconds after inhalation
- Convulsions in 30-45 seconds
- Loss of consciousness in 30 seconds
- Respiratory arrest in 3-5 minutes
- Bradycardia, hypotension, and cardiac arrest within 5-8 minutes of exposure
- Symptoms after exposure to lower vapor concentrations or after ingestion and/or liquid exposure
- May be several minutes before onset
- Feelings of apprehension or anxiety
- Vertigo
- Feeling of weakness
- Nausea with or without vomiting
- Muscular trembling
- Progression of symptoms to unconsciousness
- Headache
- Dyspnea
- Patients exposed to cyanogen chloride experience severe eye and mucous membrane irritation.
- Low-dose exposure results in rhinorrhea, bronchorrhea, and lacrimation.
- Inhalational exposure results in dyspnea, cough, and chest discomfort.
- Exposure to nitriles (acetonitrile and/or propionitrile) may be associated with a significant delay in onset of symptoms.
Physical
Physical findings are nonspecific and are similar to those of severe hypoxemia.
- Altered mental status
- Convulsions
- Hypotension
- Transient hyperpnea
- Bradypnea followed by apnea
- Cardiac dysrhythmias followed by cardiac arrest
- Severe respiratory distress in an acyanotic patient suggests possible cyanide toxicity.
- When observed, cherry-red skin suggests concomitant carbon monoxide poisoning or high venous oxygen content from failure of tissues to extract oxygen. Arterialization of the venous blood may also be noted during phlebotomy or examination of the retinal veins.
- Bright red skin and absence of cyanosis seldom are described in patients with cyanide poisoning, most likely because of concomitant cardiovascular collapse. Patients may also present cyanotic after prolonged respiratory failure and shock.
- Patients may demonstrate diaphoresis with normal or dilated pupils.
- Initial hypertension and compensatory bradycardia are followed by hypotension and tachycardia.
- Terminal hypotension is accompanied by bradyarrhythmias prior to asystole.
Causes
Causes of cyanide casualties include deliberate use as a chemical warfare agent, industrial exposures, and toxic byproducts of fires.
CBRNE - Cyanides, Cyanogen Chloride
CBRNE - Nerve Agents, Binary: GB2, VX2
CBRNE - Nerve Agents, G-series: Tabun, Sarin, Soman
CBRNE - Nerve Agents, V-series: Ve, Vg, Vm, Vx
Shock, Septic
Toxicity, Carbon Monoxide
Toxicity, Ethylene Glycol
Toxicity, Hydrogen Sulfide
Toxicity, Isoniazid
Toxicity, Organophosphate and Carbamate
Other Problems to be Considered
Consider the diagnosis of cyanide poisoning in patients with rapid collapse or seizures accompanied by metabolic acidosis and decreased oxygen consumption. Other agents that may have similar features in toxicity include the following:
Methemoglobin-inducing agents
Carbon monoxide
Inert gases (simple asphyxiants)
Hydrogen sulfide
Azides
Arsine
Phosphine
Monomethylhydrazine
Isoniazid
Water hemlock
Strychnine
Organophosphates
Metformin
Lab Studies
- Arterial and venous blood gases: Cyanide toxicity is characterized by a normal arterial PO2 and an abnormally high venous PO2 (decreased arteriovenous oxygen difference [A-VO2]).
- Serum chemistries and lactate level: Cyanide poisoning is classically associated with high anion gap metabolic acidosis and elevated lactate level.
- Cyanide levels
- Cyanide levels are generally not available in time to guide acute treatment but may be confirmatory. The preferred test is an RBC cyanide level.
- With this method, mild toxicity is observed at concentrations of 0.5-1.0 mcg/mL. Concentrations of 2.5 mcg/mL and higher are associated with coma, seizures, and death.
- Carboxyhemoglobin level: Obtain carboxyhemoglobin level of patient to exclude carbon monoxide poisoning, especially in smoke inhalation victims.
- Methemoglobin level: Obtain a methemoglobin level, especially in cyanotic patients. Also, following the treatment of cyanide poisoning with sodium nitrite, methemoglobin levels are useful (see Treatment).
Other Tests
- ECG: Shortening of the ST segment with eventual fusion of the T wave into the QRS complex has been observed.
Procedures
- Endotracheal intubation is indicated for treatment of apneic cyanide casualties.
Prehospital Care
- Appropriate prehospital measures include the following:
- Rescue from the cyanide source (assuming rescuers have the highest level of respiratory protection [Level A])
- Removal of contaminated clothing and decontamination of the skin as required with soap and water
- Administration of high-flow oxygen, airway management, and ventilatory support as required
- Establishment of intravenous access
- Continuous cardiac monitoring
- Advanced cardiac life support (ACLS) measures as indicated for dysrhythmias
- Administer cyanide antidotes as soon as possible. While generally not carried by emergency medical technicians, these may be available at certain industrial sites.
Emergency Department Care
- Continue hemodynamic support and monitoring, oxygenation, ventilatory support, and seizure control in the emergency department (ED).
- Administer cyanide antidotes (sodium nitrite and sodium thiosulfate) as soon as possible, taking care not to create toxic methemoglobinemia. Do not delay treatment for confirmatory RBC cyanide levels.
- Consider gastric lavage followed by the administration of activated charcoal in recent ingestions. The gastric aspirate may cause secondary contamination and should be viewed as hazardous.
Consultations
In any suspected terrorist attack, contact local law enforcement authorities and the Federal Bureau of Investigation. Consultation with a medical toxicologist and/or poison control center and intensivist may be useful.
The Taylor (formerly Lily or Pasadena) Cyanide Antidote Package contains amyl nitrite, sodium nitrite, and sodium thiosulfate. The nitrite components oxidize iron contained in hemoglobin to methemoglobin. This creates an additional site for cyanide binding and promotes dissociation from cytochrome oxidase. Resultant cyanomethemoglobin may then be converted to less toxic thiocyanate through enzymes such as rhodanese or other sulfurtransferases in the presence of sodium thiosulfate. Only use amyl nitrite perles as a temporizing measure if IV access has not been established, since administration of IV sodium nitrite is more effective in creating therapeutic methemoglobin levels. The use of the nitrite-containing components of the cyanide antidote kit must be done with caution, as they may result in significant hypotension and cardiovascular collapse. Production of methemoglobin reduces oxygen-carrying capacity, which in excess can be life-threatening. In the setting of concomitant carbon monoxide poisoning, use of sodium nitrite must occur with particular caution if not abandoned altogether. Patients exposed to carbon monoxide have an underlying diminished oxygen-carrying capacity; further decreased by production of methemoglobinemia may be lethal. However, in cases of smoke inhalation where cyanide toxicity is suspected, administration of sodium thiosulfate is safe. Unlike carbon monoxide, inhibition of cytochrome oxidase by cyanide is noncompetitive; therefore, oxygen has antidotal efficacy in cyanide poisoning through uncertain mechanisms. Treat patients with 100% oxygen. Hyperbaric oxygen use may be considered for patients with cyanide poisoning refractory to other antidotes; it is especially effective when concomitant carbon monoxide toxicity exists. However, its use in pure cyanide poisoning is controversial.
Hydroxocobalamin, used routinely in Europe for cyanide toxicity, can be administered when available. It functions by combining with cyanide to form cyanocobalamin, which is relatively nontoxic and cleared renally. It can be combined with sodium thiosulfate administration for accelerated detoxification.
Drug Category: Antidotes
Administration of antidotes, which counteract the toxic effects of cyanide, is critical for life-threatening intoxication. Hydroxocobalamin (vitamin B-12a) has been recognized as an antidote for cyanide toxicity for more than 40 years and is in active use in France for cyanide poisoning. It is FDA approved for the treatment of pernicious anemia and has an excellent safety profile. Hydroxocobalamin binds with cyanide on an equimolar basis to form cyanocobalamin (vitamin B-12) and thereby detoxifies the agent. However, US formulations are not sufficiently concentrated to make hydroxocobalamin a useful alternative treatment at this time. Currently, the most concentrated formulation in the United States is 1,000 mcg/mL. The typical cyanide treatment dose used in Europe is 5 g, which would require 5 L of this formulation. Hopefully, the continuing threat of CW terrorism as well as industrial accidents/fires will result in greater future efforts to establish hydroxocobalamin as the treatment of choice for cyanide toxicity in the United States as well.
| Drug Name | Amyl nitrite (Isoamyl Nitrate) |
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| Description | Ampules can be crushed and inhaled by a spontaneously breathing patient or ventilated into an apneic patient using a bag valve mask device; temporizing measure until IV access can be established. |
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| Adult Dose | 1 ampule (0.2 mL) for 30-60 s administered by inhalation along with 100% oxygen |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity, cerebral hemorrhage |
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| Interactions | Coadministration with alcohol may cause severe hypotension and cardiovascular collapse; with calcium channel blockers, may produce symptomatic orthostatic hypotension; aspirin may increase nitrate serum concentrations |
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| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
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| Precautions | Can cause severe methemoglobinemia in overdose or in those with G-6-PD deficiency; rarely may cause hemolytic anemia |
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| Drug Name | Sodium nitrite |
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| Description | DOC once IV access is established; creates methemoglobinemia more effectively than amyl nitrite. |
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| Adult Dose | 300 mg (10 mL of 3% solution) IV over 5-20 min; slow rate of infusion if hypotension develops; this dose assumes hemoglobin level of 12 mg/dL (dosage adjustment necessary in patients with anemia); may repeat up to half initial dose in 1 h if required |
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| Pediatric Dose | 0.33 mL/kg of 3% solution IV over 5-20 min, not to exceed 300 mg; this dose assumes hemoglobin level of 12 mg/dL (dosage adjustment necessary in patients with anemia) |
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| Contraindications | Documented hypersensitivity, concomitant severe carbon monoxide poisoning |
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| Interactions | Coadministration with channel blockers may increase symptomatic orthostatic hypotension (adjust dose of either agent) |
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| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
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| Precautions | Excessive methemoglobinemia, hemolysis, or hypotension may occur, especially in patients with G-6-PD deficiency |
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| Drug Name | Sodium thiosulfate (Tinver) |
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| Description | Acts as donor of sulfur, which is used as substrate by rhodanese and other sulfurtransferases for detoxification of cyanide to thiocyanate; DOC for treating cyanide toxicity with concomitant carbon monoxide poisoning. |
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| Adult Dose | 12.5 g (50 mL) IV over 10 min; may repeat up to half dose at 1 h for patients with persistent symptoms |
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| Pediatric Dose | 1.65 mL/kg of 25% solution over 10 min, not to exceed 12.5 g; may repeat up to half dose at 1 h for patients with persistent symptoms |
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| Contraindications | Documented hypersensitivity |
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| Interactions | None reported |
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| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
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| Precautions | Caution in asthma; rapid IV infusion may cause transient hypotension and ECG changes |
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| Drug Name | Hydroxocobalamin (vitamin B-12) |
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| Description | Complexes with cyanide to form nontoxic cyanocobalamin (vitamin B-12); disadvantages are large dose required for antidotal efficacy and availability in US only in very dilute solutions. |
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| Adult Dose | 4 g IV over 30 min, not to exceed 10 g; may be given more rapidly in cardiac arrest |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity |
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| Interactions | None reported |
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| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
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| Precautions | None reported for this indication |
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| Drug Name | Activated charcoal (Actidose-Aqua, Liqui-Char) |
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| Description | Emergency treatment in poisoning caused by drugs and chemicals. Network of pores present in activated charcoal adsorbs 100-1000 mg of drug per gram of charcoal. Does not dissolve in water.
For maximum effect, administer within 30 min after ingesting poison. |
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| Adult Dose | 25-100 g PO; 1 g/kg PO; or 10 times weight of ingested poison; give as susp in 4-8 oz water |
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| Pediatric Dose | <1 year: Not recommended
>1 year: Administer as in adults |
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| Contraindications | Documented hypersensitivity; poisoning or overdosage of mineral acids and alkalies |
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| Interactions | May inactivate ipecac syrup if used concomitantly; effectiveness of other medications decreases with coadministration; do not mix with sherbet, milk, or ice cream (decreases absorptive properties of activated charcoal) |
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| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
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| Precautions | Not very effective in poisonings of ethanol, methanol, and iron salts; induce emesis before giving activated charcoal; after emesis with ipecac syrup, patient may not tolerate activated charcoal for 1-2 h; can administer in early stages of gastric lavage; without sorbitol, gastric lavage returns are black |
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Further Inpatient Care
- Admit patients who present with more than minimal symptoms that resolve without treatment for observation and supportive care. Also, a 24-hour observation period is necessary for those exposed to nitriles, since delayed onset of toxicity is expected.
- Optimize oxygenation and provide continuous cardiac monitoring.
- Monitor serum lactate levels, chemistries, and arterial and/or venous blood gases.
Further Outpatient Care
- Reevaluate patients for neurologic sequelae 7-10 days after discharge from the hospital.
In/Out Patient Meds
- No additional medications beyond initial antidotes are indicated. Continue to administer oxygen as required.
Transfer
- If a patient requires transfer to a higher-level medical facility, the transferring physician should ensure availability of an ACLS emergency medical service unit that can provide continuous cardiac and hemodynamic monitoring and oxygen therapy as well as the availability of cyanide antidotes.
Complications
- Parkinsonian symptoms and other neuropsychiatric sequelae are described in survivors of severe cyanide poisoning, resulting from damage to the basal ganglia and other areas sensitive to injury. The prevalence is unknown, but patients should be given close neurologic follow-up care.
Prognosis
- Prognosis is good for patients who have only minor symptoms that do not require administration of antidotes.
- Prognosis is poor once cardiovascular collapse occurs in severe cyanide poisoning. These victims are considered expectant in a mass casualty setting.
- Prognosis is fair for patients with seizures or recent-onset apnea if antidotes can be administered rapidly. These victims are triaged "immediate" in a mass casualty setting.
Patient Education
Medical/Legal Pitfalls
- Failure to consider diagnosis of cyanide toxicity, thereby delaying administration of antidotes
- Failure to recognize concomitant carbon monoxide poisoning
- Failure to admit a patient exposed to nitriles (acetonitrile or propionitrile)
| Media file 1:
Chemical Terrorism Agents and Syndromes. Signs and symptoms. Chart courtesy of North Carolina Statewide Program for Infection Control and Epidemiology (SPICE), copyright University of North Carolina at Chapel Hill, www.unc.edu/depts/spice/chemical.html. |
 |  View Full Size Image | |
Media type: Image
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CBRNE - Cyanides, Hydrogen excerpt Article Last Updated: Mar 11, 2008
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