POTASSIUM
CYANIDE
(Strongly Suspected)
POTASSIUM
CYANIDE
CASRN: 151-50-8
http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~AAAsGay8K:1
Human Health Effects:
Human Toxicity Excerpts:
... IT IS POSSIBLE FOR CYANIDE TO CAUSE
BLINDNESS & TO DAMAGE OPTIC NERVES & RETINA. /CYANIDE/
MOST SPECIFIC PATHOLOGICAL FINDING IN ACUTE
CASES /OF CYANIDE POISONING/ IS BRIGHT RED COLOR OF VENOUS BLOOD. THIS IS
STRIKING, VISIBLE EVIDENCE OF INABILITY OF TISSUE CELLS TO UTILIZE OXYGEN ...
VENOUS BLOOD IS ONLY ABOUT 1 VOL % LOWER IN OXYGEN CONTENT THAN ARTERIAL BLOOD
... /CYANIDES/
WORKERS IN ELECTROPLATING INDUST HAVE SHOWN
DERMATITIS TO BE A PROBLEM. ALSO REPORTED WERE ITCHING, SCARLET RASH, PAPULES
... IRRITATION OF NOSE, LEADING TO OBSTRUCTION, BLEEDING, SLOUGHS AND IN SOME
CASES PERFORATION OF SEPTUM. /CYANIDES/
... ENLARGED THYROID GLANDS /WERE REPORTED/ IN
WORKERS EXPOSED TO CYANIDE SALTS IN HEAT TREATMENT OF METALS. IT WAS SUGGESTED
THAT ABSORPTION OF CYANIDE DUST & HYDROGEN CYANIDE PRODUCED BY HYDROLYSIS OF
CYANIDE SALTS, WAS FOLLOWED BY METABOLISM TO THIOCYANATE, & THAT FAILURE TO
ELIMINATE THIS ... CAUSED GOITROGENIC EFFECT. /CYANIDE SALTS/
SYMPTOMATOLOGY: 1. Massive doses may produce,
without warning, sudden loss of consciousness and prompt death from respiratory
arrest. With smaller but still lethal doses, the illness may be prolonged for 1
or more hours. 2. Upon ingestion, a bitter, acrid, burning taste is sometimes
noted, followed by a feeling of constriction or numbness in the throat.
Salivation, nausea and vomiting are not unusual ... 3. Anxiety, confusion,
vertigo, giddiness, and often a sensation of stiffness in the lower jaw. 4.
Hyperpnea and dyspnea. Respirations become very rapid and then slow and
irregular. Inspiration is characteristically short while expiration is greatly
prolonged. 5. The odor of bitter almonds may be noted on the breath or vomitus
... 6. In the early phases of poisoning, an increase in vasoconstrictor tone
causes a rise in blood pressure and reflex slowing of the heart rate. Thereafter
the pulse becomes rapid, weak, and sometimes irregular ... A bright pink
coloration of the skin due to high concentrations of oxyhemoglobin in the venous
return may be confused with that of carbon monoxide poisoning. /Cyanide/
SYMPTOMATOLOGY: 7. Unconsciousness, followed
promptly by violent convulsions, epileptiform, or tonic, sometimes localized but
usually generalized. Opisthotonos and trismus may develop. Involuntary
micturition and defecation occur. 8. Paralysis follows the convulsive stage. The
skin is covered with sweat. The eyeballs protrude, and the pupils are dilated
and unreactive. The mouth is covered with foam, which is sometimes bloodstained.
... The skin color may be brick red. Cyanosis is not prominent in spite of weak
and irregular gasping. In the unconscious patient, bradycardia and the absence
of cyanosis may be key diagnostic signs. 9. Death from respiratory arrest. As
long as the heart beat continues, prompt and vigorous treatment offers some
promise of survival. /Cyanide/
A STUDY WAS UNDERTAKEN TO ASSESS THE HEALTH
STATUS OF WORKERS EXPOSED TO CYANIDE FUMES & AEROSOLS IN A FACTORY. CYANIDE
LEVELS WERE MEASURED IN THE WORK ENVIRONMENT & IN BLOOD & URINE. SMOKERS
HAD HIGHER CONCENTRATIONS THAN NON-SMOKERS. THE HIGHEST LEVELS WERE 0.8 &
0.2 MG/CU M IN BREATHING ZONE & GENERAL WORKROOM ATMOSPHERE, RESPECTIVELY.
THE WORKERS COMPLAINED OF TYPICAL CYANIDE POISONING IN SPITE OF THE LOW CONCN.
... /CYANIDES/
A 60 year old chemist was admitted two hours
after voluntary intake of 600 mg potassium cyanide. Upon admission he was in
deep coma and bradypneic but non-cyanotic. Arterial blood gas analysis showed
severe lactic acidosis; blood cyanide concentration was well above the lethal
level. The patient was intubated and artificially ventilated with highly
hyperoxic mixtures. Specific treatment included sodium nitrite and sodium
thiosulfate. The patient recovered without sequelae despite excessive
methemoglobinemia.
An 18 year old man ingested 975 to 1,300 mg of
potassium cyanide in a suicide attempt. He was treated and survived the
poisoning episode, but then had severe parkinsonian syndrome, characterized
primarily by akinesia and rigidity. He died 19 months after the drug overdose.
At autopsy, major destructive changes were found in the globus pallidus and
putamen, whereas the melanin-containing zone of substantia nigra was intact.
This is the first clinicopatholic report of parkinsonism as a result of cyanide
poisoning.
THE TLV FOR ALKALI CYANIDES ... IS BASED ON
ADDED IRRITATION CAUSED BY ALKALINITY, SUFFICIENT TO RESULT IN EPISTAXIS
(NOSEBLEED) & NASAL ULCERATION. AIR CONCN OF CYANIDE FROM ALKALI CYANIDES
PRODUCING THIS EFFECT (NOSEBLEED) DID NOT GREATLY EXCEED 5 PPM. /ALKALI
CYANIDES/
Ingestion of potassium cyanide or sodium
cyanide causes congestion & corrosion of the gastric mucosa.
... Strong solutions are corrosive to skin
& may cause deep ulcers.
Cyanides are absorbed from the skin &
mucosal surfaces and are ... dangerous when inhaled because toxic amt are ...
absorbed through bronchial mucosa & alveoli. Symptoms, which /may/ occur ...
are giddiness, headache, palpitation, dyspnea, & unconsciousness. There may
be some evidence of local irritation from the salts & nausea & vomiting.
... Central nervous depression. ... Early electrocardiographic changes may
include atrial fibrillation, ectopic ventricular beats, and abnormal QRS complex
with T wave originating high on the R wave. Sinus bradycardia is a common
presenting sign. As cyanide levels in the blood rise, ataxia develops & is
followed by coma, convulsions, & death. /Cyanides/
Signs & symptoms of acute cyanide
poisoning reflect cellular hypoxia & are often nonspecific. Onset of
symptoms depends on dose, route, & duration of exposure. Inhalation produces
... flushing, headache, tachypnea, & dizziness ... irregular stridulous
breathing, coma, seizure, & death ... /Cyanide/
WHEN ABSORBED, /CYANIDE/ ... REACTS READILY
WITH ... CYTOCHROME OXIDASE IN MITOCHONDRIA; CELLULAR RESPIRATION IS THUS
INHIBITED & CYTOTOXIC HYPOXIA RESULTS. ... RESPIRATION IS /INITIALLY/
STIMULATED ... A TRANSIENT STAGE OF CNS STIMULATION WITH HYPERPNEA AND HEADACHE
IS OBSERVED; FINALLY THERE ARE HYPOXIC CONVULSIONS AND DEATH DUE TO RESPIRATORY
ARREST. /CYANIDE/
... IT IS POSSIBLE FOR CYANIDE TO CAUSE
BLINDNESS & TO DAMAGE OPTIC NERVES & RETINA. /CYANIDE/
VOLATILE CYANIDES /SRP: AND ALL AIRBORNE
CYANIDE SALTS/ RESEMBLE HYDROCYANIC ACID PHYSIOLOGICALLY, INHIBITING TISSUE
OXIDN & CAUSING DEATH THROUGH ASPHYXIA. CYANOGEN IS PROBABLY AS TOXIC AS
HYDROCYANIC ACID ... /CYANIDES/
CYANIDES SUCH AS ... HYDROGEN CYANIDE,
POTASSIUM CYANIDE AND SODIUM CYANIDE ARE ACUTELY POISONOUS, INTERFERING WITH
METABOLIC PROCESSES & CAUSING RAPID DEATH. IN SEVERE POISONING, PUPILS ARE
CHARACTERISTICALLY WIDELY DILATED.
... Strong solutions are corrosive to skin ...
CYANIDES SUCH AS ... HYDROGEN CYANIDE,
POTASSIUM CYANIDE AND SODIUM CYANIDE ARE ACUTELY POISONOUS, INTERFERING WITH
METABOLIC PROCESSES & CAUSING RAPID DEATH. IN SEVERE POISONING, PUPILS ARE
CHARACTERISTICALLY WIDELY DILATED.
In minimal lethal doses, cyanide affects
primarily the central nervous system. Cyanide initially stimulates the
peripheral chemoreceptors, causing increased respirations. It also promotes
slowing of the heart by stimulating the carotid body receptors. The electrical
activity of the brain may stop while the heart is still beating. /Cyanide/
The most common symptoms of a long-term
cyanide exposure that has exceeded current standards have been headache,
dizziness, nausea or vomiting, and a bitter or almond taste. Mild abnormalities
of vitamin B12, folate, and thyroid function have been noted, but symptoms did
not correlate with these changes. Other excessive exposures to cyanide have
resulted in psychosis and thyroid enlargement without symptoms of thyroid
dysfunction. Several clinical syndromes have been associated with chronic
cyanide toxicity ... . These diseases may be due to high cyanide levels,
impaired cyanide detoxification mechanisms, nutritional deficiencies, or some
combination of these factors. /Cyanide/
In serious poisonings, the skin is cold,
clammy, and diaphoretic. Cyanosis may be a late finding, since poor tissue
utilization of oxygen results in elevated venous oxygen levels. Retinal veins
and arteries may appear similar in color because of the elevated venous oxygen
level. /Cyanide/
Depression of the cardiovascular system
requires cyanide doses higher than those necessary for depression of the CNS.
Initial tachycardia occurs followed by bradycardia.. Dysrhythmias and
hypotension often precede peripheral vascular collapse. The ECG may display
striking ischemic changes; pulmonary edema may complicate severe intoxications.
/Cyanide/
The CNS is the most sensitive target organ of
cyanide poisoning, with early stimulation followed by CNS depression. Early
symptoms include lightheadedness, giddiness, tachypnea, nausea, vomiting,
feeling of neck constriction and suffocation, confusion, restlessness, and
anxiety. Initial tachypnea results from direct stimulation of carotid body
chemoreceptors followed by respiratory depression. Severe cyanide poisonings
progress to stupor, coma, opisthotonus, convulsions, fixed dilated pupils, and
death. /Cyanide/
A deadly human poison by ingestion. An
experimental poison by ocular, subcutaneous, intravenous, intramuscular, and
intraperitoneal routes
Medical Surveillance:
Initial medical examination /should include/:
a complete history and physical examination ... to detect existing conditions
that might place the exposed employee at incr risk & to establish a baseline
for future health monitoring. ... Examination of cardiovascular, nervous, &
upper resp systems, & thyroid should be stressed. The skin should be exam
for evidence of chronic disorders. ... The aforementioned medical exam should be
repeated on an annual basis. ... /Cyanides/
Pre-placement and periodic examinations should
include the cardiovascular and central nervous systems, liver and kidney
function, blood, history of fainting and dizzy spells. Blood cyanide levels may
be useful during acute intoxication. Urinary thiocyanate levels have been used
but are nonspecific and are elevated in smokers. /cyanides/
Arterial Blood Gases: Arterial blood gases may
be useful for monitoring of metabolic acidosis that can occur from cyanide
poisoning. /Cyanide/
EKG Measurement: EKG monitoring may be useful
since changes have been found with cyanide exposure. /Cyanide/
The assessment of cyanide exposure can be
accomplished through measurement of cyanide. Most information found in the
literature regarding monitoring for absorption of cyanide preferred the
measurement of blood cyanide. ... Blood Reference Ranges: Normal - non-smokers,
<0.02 ug/ml; smokers, average 0.041 ug/ml; Exposed - Levels of <0.2 ug/ml
have been found to be non-toxic; however, levels of 0.5 - 1.0 ug/ml have been
associated with tachycardia and flushing. Toxic - Levels of 1.0 - 2.5 ug/ml have
been associated with obtundation; coma and respiratory depression with levels
greater than 2.5 ug/ml; death with values greater than 3 ug/ml. Serum or Plasma
Reference Ranges: Normal - cyanide: nonsmoker, 0.004 ug/ml; smoker, 0.006 ug/ml;
Exposed - not established; Toxic - cyanide; greater than 0.1 ug/ml. Urine
Reference Ranges: Normal - not established; Exposed - not established; Toxic -
not established. /Cyanide/
Respiratory Symptom Questionnaires:
Questionnaires have been published by the American Thoracic Society and the
British Medical Research Council. These questionnaires have been found to be
useful in identification of people with chronic bronchitis, however certain
pulmonary function tests such as FEV1 have been found to be better predictors of
chronic airflow obstruction. /Cyanide/
Chest Radiography: This test is widely used
for assessing pulmonary disease. Chest radiographs have been found to be useful
for detection of early lung cancer in asymptomatic people, especially for
detection of peripheral tumors such as adenocarcinomas. However, even though
OSHA mandates this test for exposure to some toxicants such as asbestos, there
are conflicting views on its efficacy in detection of pulmonary disease.
/Cyanide/
Pulmonary Function Tests: The tests that have
been found to be practical for population monitoring include: Spirometry and
expiratory flow-volume curves; Determination of lung volumes; Diffusing capacity
for carbon monoxide; Single-breath nitrogen washout; Inhalation challenge tests;
Serial measurements of peak expiratory flow; Exercise testing. /Cyanide/
Evaluation of Peripheral Neuropathy: Nerve
conduction study; Electromyography; Quantitative sensory testing; Thermography.
/Cyanide/
Evaluation of Central Nervous System Effects:
Evaluation of CNS effects can be performed through neuropsychological
assessment, which consists of a clinical interview and administration of
standardized personality and neuropsychological tests. The areas that the
neuropsychology test batteries focus on include the domains of memory and
attention; visuoperceptual, visual scanning, visuospatial, and visual memory;
and motor speed and reaction time. There is limited data on which components of
the test batteries are best indicators of early CNS effects. /Cyanide/
Evaluation of Cranial Neuropathies: Evaluation
of cranial nerve damage, as evidenced by symptoms such as loss of balance,
visual function, smell, taste, or sensation on the face, can be accomplished
through a physical examination focusing on tests such as: Smell Assessment ...
Visual Assessment ... Facial and Trigeminal Nerve Assessment ... Vestibular
Assessment ... Hearing Assessment. /Cyanide/
Populations at Special Risk:
WORKERS WITH CHRONIC DISEASES OF KIDNEYS,
RESPIRATORY TRACT, SKIN OR THYROID ARE @ GREATER RISK OF DEVELOPING TOXIC
CYANIDE EFFECTS THAN ARE HEALTHY WORKERS. /CYANIDES/
Probable Routes of Human Exposure:
Poisoning may occur by ingestion, absorption
through injured skin or inhalation of hydrogen cyanide, liberated by action of
carbon dioxide or other acids.
... SYMPTOMS OF CHRONIC DISEASE ... REPORTED
IN ELECTROPLATERS & SILVER POLISHERS AFTER SEVERAL YEARS OF EXPOSURE.
/CYANIDES/
AMONG FUMIGATORS ... CYANIDE POISONING IS
RECOGNIZED ... /CYANIDES/
DERMATITIS ... IN WORKERS CHRONICALLY EXPOSED
TO CYANIDE SOLN. ELECTROPLATERS SUFFER FROM SUCH IRRITATION. /CYANIDE SOLN/
Body Burden:
Cyanide is present in normal healthy human
organs at concentrations ranging up to 0.5 mg/kg. /Cyanide/
Antidote and Emergency Treatment:
Due to the apparent low binding capacity of
activated charcoal for potassium cyanide (KCN) in vitro, the use of oral
activated charcoal therapy for oral exposure to cyanide compounds is
controversial. In our study, rats were given a lethal oral dose of ground
granular KCN (35 or 40 mg/kg) in a gelatin capsule followed immediately by
either 4 g/kg of superactivated charcoal in a 20% suspension or a similar volume
of deionized water. Signs of cyanide toxicosis occurred rapidly, with a mean
time to signs of 3.3 and 2.7 min in control animals receiving 35 or 40 mg/kg KCN,
respectively. All 26 of the control rats showed signs, and all but one in the 35
mg/kg group died within 19 min. Only 12 of 26 rats treated with superactivated
charcoal showed signs of KCN toxicosis and eight of those animals died.
The oxidative disposition of potassium cyanide
was studied in mice. Male Swiss-Webster mice were injected sc with 4.6 mg/kg
(14)C labeled potassium cyanide. The animals were observed for signs of
toxicity. Expired air was collected and assayed for radiolabeled hydrocyanic
acid and carbon dioxide for up to 210 min after injection. Mice were pretreated
with antidotal agents sodium nitrate, sodium thiosulfate, oxygen, alone or in
combination, or oxygen intermediates hydrogen peroxide, 3-amino-1,2,4-triazole,
superoxide dismutase, or diethyldithiocarbamic acid, and injected sc with
potassium cyanide. Expired air was assayed for radioactive hydrocyanic acid and
carbon dioxide as before. Potassium cyanide caused a transient decrease in
exploratory behavior 1 to 2 min after injection, which returned to normal within
10 min. This was accompanied by a slight decrease in respiratory rate and
dyspnea. These effects were not seen in animals pretreated with the antidotes.
Approximately 1 and 2 percent of the potassium cyanide dose was expired as
radiolabeled hydrocyanic acid and carbon dioxide, respectively. Pretreatment
with the cyanide antidotes significantly reduced expiration of the pulmonary
metabolites.
The use of the combination consisting of 4 g
of hydroxoycobalamin and 8 g of sodium thiosulfate as an antidote in cases of
cyanide poisoning is reviewed. The antidote, which has been used in France since
1970, has proved to be nontoxic and therefore can be given in cases where the
diagnosis of cyanide poisoning is not absolutely certain. On the other hand, the
Lilly Cyanide Antidote Kit, which has been approved for use in the USA for the
same purpose, has been shown to be toxic and its use requires caution. The
antidotal effectiveness of the association of hydroxoycobalamin and sodium
thiosulfate has been demonstrated in mice and other animal species poisoned with
cyanide. Most animal studies reveal a strong antidotal synergism between the two
agents. In France, the efficacy of the antidotal combination has been proved in
patients who have ingested as much as 1.5 g of potassium cyanide and have blood
cyanide levels on the order of 15 ug/ml. In the USA, the antidotal combination
is designated as an orphan drug by the FDA and studies have been started to
validate its safety and efficacy before being approved for use in this country.
/Cyanide/
A 34 year old, 73 kg man ingested a 1 g
potassium cyanide pellet in a suicide attempt. Within one hour, coma, apnea,
metabolic acidosis, and seizures developed. Sodium nitrite and sodium
thiosulfate were administered. Dramatic improvement in the clinical condition
occurred by the completion of antidote infusion. Methemoglobin level was 2%
immediately after nitrite administration. Serial whole blood cyanide levels were
obtained, documenting a highest measured level of 15.68 ug/ml. Estimations of
toxicokinetic parameters including terminal half-life (19 hr), clearance (163
ml/minute), and volume of distribution (0.41 l/kg) were calculated. The nitrite/thiosulfate
combination was clinically efficacious in this case and resulted in complete
recovery.
A coincubation system composed of hepatocytes
in primary monolayer culture and erythrocytes suspended in the culture medium
was developed and used as a model for investigations of mechanisms of cyanide
antidote action at the cellular level. Hepatocyte ATP was used as the
cytotoxicity indicator. Treatment of rat hepatocytes in the coincubation system
with potassium cyanide (KCN) (1.0 mM) for 10 min at 37 deg C selectively reduced
hapatocyte ATP levels to 33 + or - 15% of control (no KCN added) levels.
4-dimethylaminophenol, cobalt(II) chloride, sodium nitrite, sodium thiosulfate,
or a combination of the last two antidotes added to the KCN-containing medium
significantly reversed ATP depression and the response was concentration
dependent. The relative effectiveness, on a molar basis, was estimated to be
4-dimethylaminophenol greater than cobalt(II) chloride much greater than sodium
nitrite congruent to sodium thiosulfate. Sodium nitrite and
4-dimethylaminophenol induced methemoglobin formation in the absence of cyanide
and cyanomethemoglobin formation in its presence; erythrocytes were required in
the medium for effectiveness. Cobalt(II) chloride produced neither
cyanomethemoglobin nor thiocyanate in appreciable quantities nor required
erythrocytes for antagonism. Sodium thiosulfate converted cyanide to thiocyanate
and reversed ATP depression without erythrocytes in the medium. The addition of
erythrocytes increased these rates significantly and to a greater extent than
albumin.
/Experimental Therapy:/ The effect of
hemodialysis in dogs receiving a constant infusion of cyanide with and without a
simultaneous infusion of thiosulfate was studied. The hemodialysis clearance of
cyanide in the presence of thiosulfate was 38.3 + or - 5.4 ml/min with an
extraction ratio of 0.43 + or - 0.06 (n= 4). hemodialysis was found to increase
the lethal dose of cyanide without thiosulfate infusion, and a further increase
was noted with the thiosulfate infusion. Thiosulfate promotes mitochondrial
metabolism of cyanide to thiocyanate. The end product, thiocyanate, is quickly
removed by hemodialysis. The demonstrated effectiveness of hemodialysis in the
treatment of acute cyanide intoxication is related not only to the hemodialysis
clearance of cyanide, but also to the removal of its metabolic end product,
thiocyanate. /Cyanide/
Basic Treatment: Establish a patent airway.
Suction if necessary. Watch for signs of respiratory insufficiency and assist
ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15
l/min. Administer amyl nitrite ampules as per protocol and physician order ... .
Monitor for shock and treat if necessary ... . Monitor for pulmonary edema and
treat if ... . Anticipate seizures and treat if necessary ... . For eye
contamination, flush eyes immediately with water. Irrigate each eye continuously
with normal saline during transport ... . Do not use emetics. For ingestion,
rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the
patient can swallow, has a strong gag reflex, and does not drool ... . /Cyanide
and related compounds/
Advanced Treatment: Consider orotracheal or
nasotracheal intubation for airway control in the patient who is unconscious or
in respiratory arrest. Positive pressure ventilation techniques with a bag valve
mask device may be beneficial. Start an IV with D5W /SRP: "To keep
open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia
are present. Watch for signs of fluid overload. Administer cyanide antidote kit
as per protocol and physician order ... . Monitor and treat cardiac arrhythmias
if necessary ... . Consider vasopressors to treat hypotension without signs of
hypovolemia ... . Consider drug therapy for pulmonary edema ... . Treat seizures
with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye
irrigation ... . /Cyanide and related compounds/
Although a variety of agents are effective
antidotes in the experimental animal (nitrites, dimethylaminophenol, cobalt EDTA,
hydroxocobalamin, stroma-free methemoglobin solutions, pyruvate, thiosulfate,
sulfur sulfanes, mercaptopyruvate, oxygen) only the three-step Eli-Lilly cyanide
kit is approved in the US. /Cyanide/
/SRP: For patients treated with nitrites:/
Measurement of methemoglobin may be useful for assessing exposure. However,
methemoglobin levels may be artificially low if not analyzed within a few hours
after drawing the blood. Methemoglobin levels have been found to correlate with
clinical symptoms in most cases. /Cyanide/
Animal Toxicity Studies:
Non-Human Toxicity Excerpts:
... DAILY SC INJECTIONS OF POTASSIUM CYANIDE
INCR GRADUALLY TO LETHAL LEVELS HAS CAUSED NYSTAGMUS & PERIODS OF BLINDNESS
IN MONKEYS, CATS, DOGS, & RATS, WITH HISTOLOGICALLY DEMONSTRABLE
DEGENERATION IN OPTIC NERVE, CHIASM, & OPTIC TRACT.
CYANIDES SUCH AS ... HYDROGEN CYANIDE,
POTASSIUM CYANIDE AND SODIUM CYANIDE ARE ACUTELY POISONOUS, INTERFERING WITH
METABOLIC PROCESSES & CAUSING RAPID DEATH. IN SEVERE POISONING, PUPILS ARE
CHARACTERISTICALLY WIDELY DILATED.
IN AWAKE RATS, POTASSIUM CYANIDE INJECTED IP,
INCR 2,3-DIPHOSPHOGLYCERATE (DPG) BLOOD LEVELS. POTASSIUM-INDUCED INCR OF DPG
APPEARS TO CONSTITUTE A RESPONSE TO HYPOXIA.
STUDIES TO DETERMINE WHETHER MUTAGENIC
SUBSTANCES WOULD MODIFY DNA REPLICATIVE ACTIVITY WERE PERFORMED. 2.6 MG/KG OF
POTASSIUM CYANIDE DID NOT CAUSE INHIBITION OF MOUSE TESTICULAR DNA SYNTHESIS.
Pigs were allotted to 3 treatment groups
comprising a maize control ration (1), cassava peel rations (2) and a cassava
peel + dietary potassium cyanide rations (3). Diets 1-3 contained 0, 96, and 400
ppm cyanide, respectively. Feed intake and growth rate were non-significantly (p
> 0.05) reduced on cassava peel containing ration. Feed efficiency and
protein efficiency ratio on the cassava peel based rations compared favorably
with the control. Performance traits (daily weight gain, daily feed intake, feed
efficiency) were /had no effect/ (p > 0.05) with dietary cyanide level.
Nutrient digestibility was similar in all treatment groups except for ether
extract digestibility which was significantly (p > 0.05) higher on rations 2
and 3. Metabolizable energy and N retention per day were not affected by dietary
treatments.
Cumulative effects of adding 500 ppm potassium
cyanide to a cassava root flour-based diet were studied. High dietary level of
potassium cyanide did not have any marked effect in gestation and lactation
performance of female rats. No carry-over effect of level of cyanide fed during
gestation was observed on lactation performance. The high cyanide containing
diet significantly reduced feed consumption and daily growth rate of the
offspring when fed during postweaning growth. Protein efficiency ratio was
reduced by the high cyanide diet during the postweaning growth phase and there
was a carry-over effect from gestation. Serum thiocyanate was significantly
increased in lactating rats and their offspring during lactation and in the
postweaning growth phase of the pups. No apparent carry-over effect was noticed
on this parameter. Rhodanese activity in liver and kidney was unaffected by
feeding the high cyanide diet during gestation, lactation and/or during
postweaning growth.
THE ACUTE SYSTEMIC TOXICITY OF HYDROGEN
CYANIDE, SODIUM CYANIDE AND POTASSIUM CYANIDE BY INSTILLATION INTO THE INFERIOR
CONJUNCTIVAL SAC WAS INVESTIGATED. USING RABBITS, THE LD50 VALUE FOR POTASSIUM
CYANIDE WAS 0.121 MMOL/KG. SIGNS OF TOXICITY APPEARED RAPIDLY AND DEATH OCCURRED
WITHIN 3-12 MINUTES OF THE EYE BEING CONTAMINATED. THUS, FOLLOWING OCULAR
INSTILLATION, CYANIDES MAY BE ABSORBED ACROSS THE CONJUNCTIVAL BLOOD VESSELS IN
AMOUNTS SUFFICIENT TO PRODUCE SYSTEMIC TOXICITY.
IN EXPTL ANIMALS, DEMONSTRATION OF EFFECTS OF
CYANIDE POISONING ON RETINA & OPTIC NERVE HAS BEEN SUCCESSFUL PRINCIPALLY
WITH ACUTE SEVERE, NEAR-LETHAL, OR LETHAL POISONINGS. /CYANIDE/
IN RABBITS, AFTER SUBLETHAL DOSES OF CYANIDE,
CHANGES IN ELECTRORETINOGRAM HAVE BEEN OBSERVED. /CYANIDES/
Chronic implantation of surface coils on the
skull was developed to record (31)P NMR spectra of the brain in unanesthetized
rats. Ip sublethal doses induced strong and reversible changes in high-energy
phosphate compounds in the brain, similar in part to those induced by ischemia.
These effects were dose-dependent as far as phosphocreatine, inorganic
orthophosphates, and pH were concerned; ATP does not seem to be altered by
potassium cyanide doses of 3-5 mg/kg, but decreased at 6 mg/kg. The fraction of
Mg(2+)-complexed ATP (approximately 90%) was not affected by potassium cyanide
intoxication.
Hepatic hexose transport was characterized in
rats using 3-O-methyl-D-glucose, which is not metabolized by the liver. The
effects of N2-induced anoxia and of potassium cyanide were investigated. In the
fasted state, anoxia caused the transport characteristics Vmax and Km to
decrease nearly 2 fold whereas potassium cyanide had the opposite effect as the
Vmax and Km were increased by 3 and 2 fold, respectively. In the fed state,
anoxia and potassium cyanide caused a marked decrease in the transport
characteristics.
The effect of cyanide on whole-brain calcium
levels was determined in mice administered potassium cyanide and correlated with
the neurotoxic signs manifested during acute cyanide poisoning. Potassium
cyanide (10 mg/kg, sc) significantly increased whole-brain total calcium levels
from 48.1 + or - 1.8 to 66.5 + or - 3.9 micrograms/g dry wt within 15 min after
administration. They remained elevated for 3 hr and returned to control readings
after 12 hr. Dose-response studies revealed potassium cyanide at doses of 10-15
mg/kg, produced significant elevations of whole-brain calcium 30 min after
administration. No measurable effect was obtained from lower doses which
suggested a threshold effect. Pretreatment 15 min before potassium cyanide with
diltiazem, a calcium channel blocker, prevented the cyanide induced rise in
whole-brain total calcium. Cyanide induced tremors, which are centrally mediated
symptoms of intoxication, were quantified and correlated with the observed
changes in whole-brain calcium. Tremors were detected at 10 and 12 mg/kg
potassium cyanide and peak intensity was observed at 15 min postcyanide.
Pretreatment with diltiazem markedly attenuated the cyanide induced tremors. It
appears that a correlation exists between cyanide induced change in whole-brain
calcium and tremors. This study suggests that intraneuronal calcium may play an
important role in mediating cyanide neurotoxicity and calcium channel blocking
agents may be useful in limiting the severity of the centrally mediated symptoms
of acute cyanide intoxication.
A starfish sperm bioassay for detecting
chemical pollutants is described. Potassium cyanide and mercurous chloride
inhibited oxygen consumption of spermatozoa by 50% at 0.07 ng/ml and 0.3 ng/ml
respectively.
Cyanide (2 mM), an inhibitor of cytochrome
oxidase, diminished p-nitroanisole O-demethylation by 50-75% in perfused livers
from normal and phenobarbital-treated rats, but had much less effect on hepatic
microsomal p-nitroanisole O-demethylation. The inhibition was also observed in
livers where the activity of the pentose phosphate shunt was abolished by
pretreatment with 6-aminonicotinamide. Cyanide infusion decreased hepatic
ATP/ADP ratios and cellular concentrations of glutamate, alpha-ketoglutarate,
and isocitrate, but caused an increase in the NADP+/NADPH ratio. Rates of NADPH
generation via the pentose phosphate shunt were unchanged by cyanide, and
hepatic concentrations of glucose 6-phosphate were markedly increased by
cyanide. Thus, inhibition of p-nitroanisole metabolites could not be explained
solely by a direct interaction of cyanide with mixed-function oxidases or
diminished NADPH generation via the pentose cycle. Apparently cyanide inhibits
mixed-function oxidation in intact cells by diminishing the generation of NADPH
from sources other than the pentose cycle. Further, these data are consistent
with the hypothesis that some NADPH for mixed-function oxidation arises from
cyanide-sensitive mitochondrial sources.
IN THE CASE OF HYDROCYANIC ACID AND CYANIDES
/IN VERY HIGH DOSES/, DEATH USUALLY OCCURS /IN ANIMALS/ WITHIN A FEW SECONDS:
THERE MAY BE CONVULSIONS, PARALYSIS, STUPOR, & CESSATION OF RESPIRATION
BEFORE THAT OF HEARTBEATS. /CYANIDES/
... IF ... ANIMALS ... HAVE EATEN CYANOGENIC
PLANTS, CLINICAL SIGNS MAY VARY FROM MILD TACHYPNEA & APPARENT ANXIETY TO
SEVERE PANTING, GASPING, & BEHAVIORAL ALARM. OTHER SIGNS INCL SALIVATION,
MUSCLE TREMORS, LACRIMATION, URINATION & DEFECATION, SEVERE COLIC, EMESIS,
PROSTRATION, ... CLONIC CONVULSIONS, MYDRIASIS, & RAPID DEATH. ... MUCOUS
MEMBRANES ARE ... PINK & BLOOD IS CHERRY RED & MAY NOT CLOT. RED COLOR
IS DUE TO HYPEROXYGENATION THAT OCCURS WHILE THE ANIMAL IS DYING. THERE MAY BE
AGONAL HEMORRHAGES ON HEART. GI TRACT & LUNG MAY HAVE CONGESTION &
PETECHIAL HEMORRHAGES. /CYANOGENIC PLANTS/
Except for the more sensitive invertebrate
species, such as Daphnia pulex and Gammarus pseudolimnaeus, invertebrate species
are usually more tolerant of cyanide than are freshwater fish species, which
have most acute values clustered between 50 to 200 ug/l. A long-term survival
and two life cycle test with fish gave chronic values of 7.9, 14, and 16 ug/l,
respectively, with Gammarus pseudolimnaeus being comparable to fish in
sensitivity and isopods being considerably more tolerant. /Free cyanide: HCN and
CN-/
... /THERE IS A/ COMBINED EFFECT OF PULMONARY
EDEMA AND THE INTERFERENCE OF CELLULAR METABOLISM BY THE CYANIDE ION. /CYANIDE
ION/
Lipid peroxidation of brain lipids as
determined by the conjugated diene method was observed in mice following
administration of sublethal doses of potassium cyanide (KCN). Conjugated diene
production was dose and time dependent; 10 mg/kg KCN produced detectable levels
of conjugated dienes at 30 min post cyanide, whereas, 15 mg/kg produced marked
levels of conjugated dienes over a 10-60 min period after KCN. Pretreatment of
mice with either diltiazem (600 micrograms/kg, iv) or allopurinol (255 mg/kg,
iv) blocked the generation of conjugated dienes.
The effect of cyanide on the active
intracellular calcium pool was studied in a cultured neurosecretorycell line,
PC12, derived from a rat pheochromocytoma. Cells were cultured and loaded with
Quinn-II. Potassium cyanide (KCN) was added to the cultures at concentrations
from 10(-4) molar to 10(-2) molar and the intracellular calcium concn was
measured. Results showed that KCN produced a rise in cytosolic calcium which was
dose dependent. Concn of KCN below 10(-4) molar did not produce measurable
increases. The effect of KCN on cell viability was assessed using trypan blue
exclusion. No effect was seen at the lower doses of KCN, but at 10(-2) molar a
significant decrease in live cells was observed after 30 mins.
Brain cytochrome responses to carbon monoxide
and cyanide were studied in rats. Male Sprague-Dawley rats were surgically
prepared for in vivo brain differential reflectance spectrophometry. After
preparation, they were intravenously infused with potassium cyanide at rates of
0.25 to 0.50 mg/kg/min, allowed to recover, and then exposed to gas mixtures
containing 0,1,3 or 5 percent carbon monoxide in oxygen. Some animals were
pretreated with antimycin-A. Cortical spectra were obtained and cytochrome
reduction/oxidation changes were monitored. In an in vitro experiment,
hemoglobin free rat brain slices were incubated with potassium cyanide and
carbon monoxide. Cytochrome responses were investigated by transmission
spectrophotometry. In vivo, cyanide infusion caused reversible increases in the
reduction level of cytochrome-a3, measured at 605 to 620 nm. The
oxidation/reduction state of b-type cytochromes, monitored at 564 to 575 nm,
remained stable during most cyanide infusions. Reduction responses to cyanide
were seen after exposure to 1 to 5 percent carbon monoxide. The a3-type and
c-type cytochromes did not increase their reduction levels during exposure to 5
percent carbon monoxide. In vitro, b-type cytochromes were stable when exposed
to cyanide. After reduction with carbon monoxide, a 445 nm spectral component
was found that bound carbon monoxide in the presence of 1 mM potassium cyanide.
Brain cytochrome oxidase activity was measured
after the in vitro addition of potassium cyanide (KCN) or sodium nitroprusside.
Activity of cytochrome oxidase was sensitive to KCN; however, this activity was
unaffected by sodium nitroprusside. In sodium nitroprusside and KCN treated
animals brain cytochrome oxidase activities were measured. At 3 min after sodium
nitroprusside injection, inhibition of the enzymatic activity was the same as 1
min after KCN injection. Time to death for sodium nitroprusside treated animals
was longer than for KCN treated animals.
10 MG/KG IP POTASSIUM CYANIDE (KCN) DECR
CYTOCHROME OXIDASE ACTIVITY IN MOUSE LIVER & BRAIN. WHEN ANIMALS WERE
PRETREATED WITH SODIUM THIOSULFATE & SODIUM NITRITE, KCN INHIBITED BRAIN
CYTOCHROME OXIDASE IN CONTRAST TO NO INHIBITION OF LIVER CYTOCHROME OXIDASE.
The cyanide ion is detoxified so effectively
if intake is gradual that rats were able to consume potassium cyanide at a rate
of 250 mg/kg/day without injury when the compound was mixed evenly into their
dry diet.
Non-Human Toxicity Values:
LD50 Rat oral 5 mg/kg
LD50 Rat ip 4 mg/kg
LD50 Rat sc 9 mg/kg
LD50 Rat iv 3600 mg/kg
LD50 Mouse oral 8500 ug/kg
LD50 Mouse ip 5991 ug/kg
LD50 LD50 Mouse sc 6500 ug/kg
LD50 Mouse iv 2600 ug/kg
LD50 Dog sc 6 mg/kg
LD50 Dog iv 5 mg/kg
LD Rabbit oral 5 mg/kg
LD50 Rabbit sc 4 mg/kg
LD50 Rabbit im 3256 ug/kg
LD50 Rabbit oc 7870 ug/kg
LD50 Guinea pig im 4 mg/kg
Inorganic cyanides are acutely toxic
compounds, for example, the LD50 in the rat is ... 10 mg/kg for potassium
cyanide (KCN).
Metabolism/Pharmacokinetics:
Metabolism/Metabolites:
... CYANIDE ION IS CONJUGATED WITH SULFUR TO
FORM THIOCYANATE. ... CONJUGATION IS CATALYZED BY ... RHODANESE WHICH IS WIDELY
DISTRIBUTED IN MOST ANIMAL TISSUES ... /LIVER/ PARTICULARLY ACTIVE. ...
RHODANESE MECHANISM IS CAPABLE OF DETOXICATING ONLY LIMITED AMT OF CYANIDE, SUCH
AS ARE FORMED DURING NORMAL METAB. /ANOTHER SULFUR DONOR IS 3-MERCAPTOPYRUVATE.
THE ENZYME, MERCAPTOSULFUR TRANSFERASE IS LOCALIZED IN CYTOSOL./ /CYANIDE/
THE EXCRETION OF THIOCYANATE FOLLOWING THE
ADMINISTRATION OF EQUITOXIC DOSES OF CYANIDE TO UNPROTECTED MICE AND TO ANIMALS
PRETREATED WITH VARIOUS CYANIDE ANTIDOTES WAS STUDIED. CYANIDE GIVEN ALONE OR TO
ANIMALS PRETREATED WITH THIOSULFATE IS EXTENSIVELY CONVERTED TO THIOCYANATE. THE
CYANIDE IS EXCRETED IN THE URINE, AS DEMONSTRATED BY DETECTION OF HIGH AMOUNTS
OF COBALT IONS AND STRONGLY COMPLEX-BOUND CYANIDE IN THE URINE. A METHOD FOR THE
DETERMINATION OF CYANIDE PRESENT AS COBALT CYANIDE COMPLEXES IS DESCRIBED AND
ITS FORENSIC APPLICATION IS PROPOSED.
Aliphatic nitriles have been postulated to
manifest their toxicity through cyanide (CN)
liberation. The signs of toxicity and effect of equitoxic LD50 doses of
saturated and unsaturated aliphatic mono- and dinitriles on tissue and blood CN
levels, tissue glutathione levels and cytochrome c oxidase activities were
studied in rats. Signs of toxicity were classified into cholinomimetic effects
observed with unsaturated nitriles and CNS effects observed with saturated
potassium cyanide. Hepatic and blood CN levels 1 hr
after treatment were highest following malononitrile and decreased in the order
of propionitrile > potassium cyanide > butyronitrile > acrylonitrile
> allylcyanide > fumaronitrile > acetonitrile. The order differed in
brain where potassium cyanide preceded malononitrile and PCN. Hepatic and
cytochrome c oxidase were significantly inhibited and corresponded to their CN
levels. No significant inhibition of cytochrome c oxidase was observed in vitro.
Acrylonitrile was the only nitrile which significantly reduced tissue GSH
levels. Toxic expression of aliphatic nitriles depended on CN
release and their degree of unsaturation. With unsaturated aliphatic nitriles CN
release played a minimal role in their toxicity. /Cyanides/
Rhizopus oryzae, a mucoraceous fungus
associated with the postharvest spoilage of cassava was found to effectively
metabolize cyanide. Degradation of cyanogenic glycosides of cassava by R oryzae
was studied by growing the organism in potato dextrose broth with and without
linarmarin and potassium cyanide. The influence of adaptation of the organism to
low and high cyanide concentrations on both growth and the release of
extracellular rhodanese into cyanide containing media was studied. Nonadapted
cultures of R oryzae grow poorly when compared with the cyanide adapted
cultures. However non-adapted R oryzae cultures released large quantities of
rhodanese when compared with the adapted ones. Potassium cyanide (1.0 mM) was
found to be an efficient inducer of rhodanese whereas potassium cyanide (5.0 mM)
repressed the release of rhodanese. A significant inductive effect was produced
by thiosulphate and thiocyanate.
Acute toxicity and metabolism of 7 dinitriles
in mice was studied in relation to the chemical structures. The oral LD50 for
each nitrile was detected under different conditions for mice pretreated with
either carbon tetrachloride (CCl4) or olive oil. All test nitriles were
metabolized into cyanide in vivo and in vitro. The cyanide level was variable
among the compounds (0.35-0.74 ug cyanide/g brain) at death in the brains of
mice, the level from malononitrile and adiponitrile being comparable to that
found in mice killed by dosing with potassium cyanide. After receiving each
nitrile, the mean survival time of mice pretreated with CCl4 was prolonged and
their brain cyanide level decreased when compared with the corresponding
control. With malononitrile, the former did not significantly change and the
latter decreased slightly. Brain cyanide levels of control mice at death showed
a peak at the lower log P region, whereas those of CCl4 pretreated animals
remained lower independently of log P, with the exception of malononitrile.
Microsomal metabolism of nitriles to cyanide was greatly inhibited when
microsomes were prepared from livers of mice pretreated with CCl4. The
relationship between log (1/LD50-CCl4), LD50 in mice pretreated with CCl4, and
log P fits a parabolic plot. /Cyanides/
/ONE OF/ THE MAJOR MECHANISM/S/ FOR REMOVING
CYANIDE FROM THE BODY IS ITS ENZYMATIC CONVERSION, BY THE MITOCHONDRIAL ENZYME
RHODANESE (TRANSSULFURASE), TO THIOCYANATE, WHICH IS RELATIVELY ... /LESS
TOXIC/. /CYANIDE/
RUMINANTS ARE MORE SUSCEPTIBLE TO POISONING BY
CYANOGENIC PLANTS /SRP: WHICH RELEASE HYDROGEN CYANIDE/ THAN ARE HORSES &
PIGS ... /CYANOGENIC PLANTS/
FACTORS THAT INCR LIKELIHOOD OF HYDROGEN
CYANIDE POISONING FROM INGESTION OF CYANOGENIC PLANTS INCLUDE: (1) LARGE AMT OF
FREE HYDROGEN CYANIDE & CYANOGENIC GLYCOSIDE IN PLANT, (2) RAPID INGESTION;
(3) INGESTION OF A LARGE AMT OF PLANT, & (4) RUMINAL PH & MICROFLORA
THAT CONTINUE TO HYDROLYZE GLYCOSIDE /SRP: TO RELEASE HYDROGEN CYANIDE/. RAPID
INTAKE OF PLANT ... EQUIV TO ABOUT 4 MG HYDROGEN CYANIDE/KG OF BODY WT IS
CONSIDERED TO BE LETHAL AMOUNT OF PLANT MATERIAL. ... /CYANOGENIC PLANTS/
The role of oxidative metabolism in the
disposition of potassium cyanide, was investigated in mice administered
potassium cyanide (4.6 mg/kg, sc) containing 4.5 uCi (14)C-potassium cyanide.
The expired pulmonary metabolites, (14)C-hydrocyanic acid and (14)CO2, carbon
dioxide were collected and analyzed. Approximately 1% and 2% of the potassium
cyanide dose was expired as (14)C-hydrocyanic acid and (14) carbon dioxide
respectively. Expiration of the pulmonary metabolites was decreased following
pretreatment with sodium nitrite, sodium thiosulfate, oxygen, or a combination
of cyanide antidotes. Treatment with hydrogen peroxide lowered the amount of
(14)C-hydrocyanic acid expired and did not alter the expiration of (14)carbon
dioxide. Treatment with 3-amino-1,2,4-triazole (catalase inhibitor), superoxide
dismutase, or diethyldithiocarbamic acid (superoxide dismutase inhibitor) did
not change the amount of (14)C-hydrocyanic acid expired. However, superoxide
dismutase significantly increased the amount of (14)CO2 expired, whereas
diethyldithiocarbamic acid decreased (14) carbon dioxide expiration.
Absorption, Distribution & Excretion:
IN 30 DAYS, 72% OF (14)C FROM IP DOSE OF
(14)C-CYANIDE TO MICE WAS EXCRETED IN URINE & FECES, 25% IN EXPIRED AIR,
& 3% WAS RETAINED ... PEAK EXCRETION OCCURRED WITHIN 10 MIN IN EXPIRED AIR
& WITHIN 6-24 HR IN URINE & FECES. /CYANIDE/
CYANIDE ION IS READILY ABSORBED AFTER ORAL OR
PARENTERAL ADMIN. PROLONGED LOCAL CONTACT WITH CYANIDE SOLN ... MAY RESULT IN
ABSORPTION OF TOXIC AMT THROUGH SKIN. PART OF ABSORBED CYANIDE IS EXCRETED
UNCHANGED BY THE LUNG. LARGER PORTION ... CONVERTED BY SULFURTRANSFERASE TO
RELATIVELY NONTOXIC THIOCYANATE ION. /CYANIDE/
AFTER IM INJECTION OF POTASSIUM CYANIDE AT 10
MG(CN)/KG IN SHEEP, THE CN
CONCN IN WHOLE BLOOD WAS 2-3 TIMES AS HIGH AS IN PLASMA, SERUM, CEREBROSPINAL
FLUID, CAUDATE NUCLEUS & WHITE MATTER.
The excretion of (14)C-labeled cyanide in rats
exposed to chronic intake of potassium cyanide was studied in rats exposed to
daily intake of labeled potassium cyanide in the diet for 6 weeks. Urinary
excretion was the main route of elimination of cyanide carbon in these rats,
accounting for 83% of the total excreted radioactivity in 12 hr and 89% of the
total excreted radioactivity in 24 hr. The major excretion metabolite of cyanide
in urine was thiocyanate, and this metabolite accounted for 71 and 79% of the
total urinary activity in 12 hr and 24 hr, respectively. When these results were
compared with those observed for control rats, it was clear that the mode of
elimination of cyanide carbon in both urine and breath was not altered by the
chronic intake of cyanide.
CYANIDES ARE RAPIDLY ABSORBED FROM SKIN &
ALL MUCOSAL SURFACES & ARE MOST DANGEROUS WHEN INHALED, BECAUSE TOXIC AMT
ARE ABSORBED WITH GREAT RAPIDITY THROUGH BRONCHIAL MUCOSA & ALVEOLI.
/CYANIDES/
Cyanide is distributed to all organs and
tissues via the blood, where its concn in red cells is greater than that in
plasma by a factor of two or three. Presumably, the accumulation of cyanide in
erythrocytes is a reflection of its binding to methemoglobin. /Cyanides/
Once absorbed into the body, cyanide can form
complexes with heavy metal ions. /Cyanide/
Inhalation of cyanide salt dusts is dangerous
because the cyanide will dissolve on contact with most mucous membranes and be
absorbed into the bloodstream. /Cyanide salts/
Cyanide is concentrated in red blood cells at
a RBC/plasma ratio is 100/l. The volume of distribution of cyanide ion is
approximately 1.5 l/kg. About 60% if CN- in plasma is
protein bound. /Cyanide/
Biological Half-Life:
Half-life for the conversion of cyanide to
thiocyanate from a non-lethal dose in man is between 20 min and 1 hr. /Cyanide/
Mechanism of Action:
CYANIDE HAS A VERY HIGH AFFINITY FOR IRON IN
FERRIC STATE. WHEN ABSORBED IT REACTS READILY WITH ... IRON OF CYTOCHROME
OXIDASE IN MITOCHONDRIA; CELLULAR RESPIRATION IS THUS INHIBITED & CYTOTOXIC
HYPOXIA RESULTS. SINCE UTILIZATION OF OXYGEN IS BLOCKED, VENOUS BLOOD IS
OXYGENATED AND IS ALMOST AS BRIGHT RED AS ARTERIAL BLOOD. RESPIRATION IS
STIMULATED BECAUSE CHEMORECEPTIVE CELLS RESPOND AS THEY DO TO DECREASED OXYGEN.
A TRANSIENT STAGE OF CNS STIMULATION WITH HYPERPNEA AND HEADACHE IS OBSERVED;
FINALLY THERE ARE HYPOXIC CONVULSIONS AND DEATH DUE TO RESPIRATORY ARREST.
/CYANIDE/
SINGLE DOSES OF CYANIDE PRODUCE ALTERATIONS IN
PATTERN OF BRAIN METABOLITES CONSISTENT WITH DECR IN OXIDATIVE METABOLISM &
INCR IN GLYCOLYSIS. DECR IN BRAIN GAMMA-AMINOBUTYRIC ACID ... HAVE BEEN ASCRIBED
TO CYANIDE INHIBITION OF GLUTAMIC ACID DECARBOXYLASE. /CYANIDE/
THE CORTICAL GRAY MATTER, HIPPOCAMPUS (H1),
CORPORA STRIATA, & SUBSTANTIA NIGRA ARE COMMONLY AFFECTED /BY CYANIDE/. ...
CYANIDE ALSO HAS PROPENSITY FOR DAMAGING WHITE MATTER, PARTICULARLY CORPUS
CALLOSUM. CYANIDE INHIBITS CYTOCHROME OXIDASE & PRODUCES CYTOTOXIC ANOXIA,
BUT ALSO CAUSES HYPOTENSION THROUGH ITS EFFECTS ON HEART. /CYANIDE/
The cyanide ion (CN-)
forms complexes with a number of other chemicals (eg, in tissues) and has a
strong affinity for cobalt. /Cyanide ion/
The effect of cyanide on whole-brain calcium
levels was determined in mice administered potassium cyanide and correlated with
the neurotoxic signs manifested during acute cyanide poisoning. potassium
cyanide (10 mg/kg, sc) significantly increased whole-brain total calcium levels
from 48.1 + or - 1.8 to 66.5 + or - 3.9 micrograms/g dry wt within 15 min after
administration. They remained elevated for 3 hr and returned to control readings
after 12 hr. Dose-response studies revealed potassium cyanide at doses of 10-15
mg/kg, produced significant elevations of whole-brain calcium 30 min after
administration. No measureable effect was obtained from lower doses which
suggested a threshold effect. Pretreatment 15 min before potassium cyanide with
diltiazem, a calcium channel blocker, prevented the cyanide induced rise in
whole-brain total calcium. Cyanide induced tremors, which are centrally mediated
symptoms of intoxication, were quantified and correlated with the observed
changes in whole-brain calcium. Tremors were detected at 10 and 12 mg/kg
potassium cyanide and peak intensity was observed at 15 min postcyanide.
Pretreatment with diltiazem markedly attenuated the cyanide induced tremors.
/CYANIDE/ ... REACTS ... WITH TRIVALENT IRON
OF CYTOCHROME OXIDASE IN MITOCHONDRIA TO FORM THE CYTOCHROME OXIDASE-CN
COMPLEX ... THE CYTOCHROME-OXIDASE-CN COMPLEX IS
DISSOCIABLE; THE MITOCHONDRIAL ENZYME SULFURTRANSFERASE ... MEDIATES TRANSFER OF
SULFUR FROM THIOSULFATE TO CYANIDE ION. THUS, THIOCYANATE IS FORMED ... KINETIC
STUDIES INDICATE THAT THE CLEAVAGE OF THE THIOSULFATE SULFUR-SULFUR BOND IS THE
RATE-LIMITING STEP IN THIS REACTION. RELATIVELY MINOR PATHWAYS INCL COMBINATION
WITH CYSTINE TO FORM 2-IMINO-THIAZOLIDINE-4-CARBOXYLIC ACID, OXIDATION TO CARBON
DIOXIDE & FORMATE, & FORMATION OF CYANOCOBALAMIN. /CYANIDE/
Interactions:
CHLORPROMAZINE ANTAGONISM OF CYANIDE
INTOXICATION WAS POTENTIATED BY SODIUM THIOSULFATE. CHLORPROMAZINE & SODIUM
NITRITE DID NOT PROTECT AGAINST KCN LETHALITY BETTER THAN NITRITE ALONE.
To elucidate the interaction of carbon
monoxide (CO) and cyanide, the fluorescence which represents the intracellular
reduced pyridine nucleotide was measured on the rabbit kidney surface in situ.
Various doses of potassium cyanide, 2-8 umol/kg, were administered intravenously
with and without inhalation of 1, 2 and 3% carbon monoxide via a respirator. The
dose-response relationship between potassium cyanide and the fluorescence
increase fitted a salient sigmoid curve with a steep slope, and carbon monoxide
was potent to increase fluorescence independently and shifted the dose response
curve for potassium cyanide to the left. The combined effect of carbon monoxide
and potassium cyanide was of a critical dose for intracellular respiration, it
had the appearance of synergism.
Previous reports indicated that prophylactic
protection against cyanide intoxication in mice can be enhanced by
administration of chlorpromazine when it is given with sodium thiosulfate. The
mechanism of potentiation of sodium thiosulfate by chlorpromazine was studied
alone and in combination with sodium nitrite. Although chlorpromazine was found
to induce a hypothermic response, the mechanism of enhancement of the antagonism
of cyanide by chlorpromazine does not correlate with the hypothermia produced.
Various other possible mechanisms were investigated, such as rate of
methemoglobin formation, enzymatic activity of rhodanese and cytochrome oxidase,
and alpha-adrenergic blockade. The alpha-adrenergic blocking properties of
chlorpromazine may provide a basis for its antidotal effect, since this
protective effect can be reversed with an alpha-antagonist, methoxamine.
/Cyanide/
The interaction of 7 beta-adrenergic blocking
agents with salbutamol and isoproterenol was studied in the potassium cyanide
test in rats. Salbutamol (albuterol) was used at a dose that provided protection
from potassium cyanide (KCN) lethality and isoproterenol at an overdose that
failed to protect, presumably because of latent cardiotoxicity. Salbutamol-induced
protection was abolished by drugs at the following doses (sc, mg/kg); timolol
(0.0085), bunolol (0.010), propranolol (0.038), pindolol (0.15), metoprolol
(3.93), atenolol (5.69), and practolol (>10.0). Survival was restored dose
dependently in isoproterenol-overdosed rats only by atenolol (0.44), practolol
(0.51) and metoprolol (1.06). The cardioselectivity ratio (ie, salbutamol
antagonism/isoproterenol antagonism) for these 3 compounds was as follows:
practolol (>19.6), atenolol (12.9), and metoprolol (3.82).
Cysteine, a sulfur-containing amino acid, is
required to metabolize ascorbic acid (as ascorbate sulfate) and detoxify cyanide
(to thiocyanate). In guinea pigs, concomitant use of laetrile (a cyanogenic
glycoside) and ascorbic acid (in large doses) decreases the detoxification of
cyanide derived from laetrile through diminishing the availability of cysteine,
but not impairing hepatic rhodanese activity, which is involved in the
detoxification of cyanide to thiocyanate. These results agree with the symptoms
of a sublethal dose of potassium cyanide toxicity manifested by the animals.
Flunarizine is a calcium entry blocking drug
possessing antihypoxic activity in animal models of cerebral and peripheral
ischemia-anoxia and has clinical usefulness in circulatory disorders of both
central and peripheral origin. This report compares the activity of flunarizine
and verapamil, another calcium entry blocking drug, on the central nervous
system (CNS) and peripheral consequences of cytotoxic hypoxia induced by high
and low doses of KCN. The lethal effect of potassium cyanide (6 mg/kg, ip) in
rats was prevented by orally administered flunarizine (ED50= 12 mg/kg with four
hr pretreatment) but not by verapamil (at oral doses up to 80 mg/kg with one hr
pretreatment). Since the lethal effect of KCN involves failure of respiration at
the CNS level, these results suggest that flunarizine protects against the
hypoxic effect of the cyanide ion by an action in brain tissue. We found also
that the stimulant effect of low intravenous doses (0.5 mg/kg/min) of KCN upon
respiration rate was not altered in pentobarbital- and chloralose-anesthetized
rats treated with oral doses of flunarizine up to 80 mg/kg (with four hr
pretreatment). In contrast, KCN-stimulated respiration rate in pentobarbital
anesthetized rats was significantly attenuated by verapamil (20 and 40 mg/kg, po
with one hr pretreatment). Since low doses of the cyanide ion render respiration
quicker and deeper by an action on chemoreceptive cells in peripheral arteries,
the effect of verapamil against the hypoxic effect of KCN is mediated by an
action in the periphery.
The anti-anoxic effect of sufoxazine was
investigated in various cerebral anoxia models with mice, in comparison with
those of various cerebroactive drugs. Sufoxazine reduced dose-dependently the
duration of coma induced by a sublethal dose of potassium cyanide (1.8 mg/kg,
iv) significantly stimulating recovery from the coma at 5 mg/kg, ip and 30
mg/kg, po. It also protected against a lethal dose of KCN (2.5 mg/kg, iv). These
findings suggest that sufoxazine has an anti-anoxic action superior to those of
the other cerebroactive drugs used.
Cyanide intoxication in mice can be
antagonized by the opiate antagonist, (-)naloxone HCl, alone or in combination
with sodium thiosulfate and/or sodium nitrite. Potency ratios, derived from LD50
values, were compared in groups of mice pretreated with sodium nitrite (sc, 100
mg/kg), sodium thiosulfate (ip, 1 g/kg), and (-)naloxone HCl (sc, 10 mg/kg)
either alone or in various combinations. These results indicate that naloxone
HCl provides a significant protection against the lethal effects of potassium
cyanide. The protective effect of sodium thiosulfate, but not sodium nitrite,
was enhanced with (-)naloxone HCl. The combined administration of sodium nitrite
and sodium thiosulfate was further enhanced with (-)naloxone HCl. The protective
effect of naloxone HCl against the lethal effect of cyanide appears to be
restricted to the (-)stereoisomer, as the (+)stereoisomer, the inactive opiate
antagonist, is also inactive in protecting against the lethal effects of
cyanide.
Protective effects of OP-2507
(15-cis-(4-propylcyclohexyl)16,17,18,19,20-pentanor-9-deoxy-9 alpha,
6-nitrilo-PGF1 methyl ester) against cerebral anoxia and edema were investigated
in a variety of experimental models in mice and rats. OP-2507 given sc or po led
to a consistent and dose-dependent prolongation of survival time against
cerebral anoxia in hypobaric and normobaric hypoxia, potassium cyanide induced
anoxia.
Pyruvic acid, an alpha-ketocarboxylic acid,
has been shown to antagonize the lethal effects of cyanide. It is suggested that
its mechanism of action rests in its ability to react with or "bind"
cyanide. alpha-Ketoglutaric acid increased the LD50 value of cyanide (6.7 mg/kg)
by a factor of five, a value statistically equivalent to that ascertained in
mice pretreated with sodium thiosulfate and sodium nitrite. The combination of
alpha-ketoglutaric acid and sodium thiosulfate increased the LD50 value of
cyanide to 101 mg/kg. Addition of sodium nitrite to the alpha-ketoglutaric
acid/sodium thiosulfate regimen increased the LD50 value of cyanide to 119
mg/kg. Unlike sodium nitrite, no induction of methemoglobin formation was
observed with alpha-ketoglutaric acid pretreatment.
The activity of a series of 9 beta-adrenergic
agonists was studied in the potassium cyanide (5.00 mg/kg iv) and the compound
48/80 (0.50 mg/kg iv) lethality tests in rats. All compounds were active in both
tests. The ED50 values in mg/kg for protection against KCN-induced lethality
were as follows: clenbuterol (0.0047), zinterol (0.0055), hexoprenaline
(0.0093), fenoterol (0.012), isoproterenol (0.014), colterol (0.019), salbutamol
(0.028), terbutaline (0.14), and metaproterenol (0.33). By increasing the dose
levels, the protective activity of some of the compounds disappeared and LD50s
at which lethality to KCN was restored could be calculated. The protective dose
range, which is defined as the ratio of the LD50 and the ED50, greatly varies
among the test compounds. Protection from KCN induced lethality seems to be due
to an increased tissue perfusion and to occur as long as myocardial activity is
not markedly changed from normal by the test compound.
The purpose of this study was to investigate
lethality induced by low concentrations of carbon monoxide and cyanide. Male ICR
mice were used in these studies. Doses of potassium cyanide (4-9 mg/kg, ip) were
administered to animals pretreated for 3 min with either air or carbon monoxide
(0.63-0.66%). From these data the LD50 value of potassium cyanide (KCN) was
determined in these animals pretreated with either air or carbon monoxide. A
significantly lower LD50 value for KCN was found in carbon monoxide pretreated
animals as compared to air pretreated animals. In another series of experiments,
animals were pretreated with either saline or KCN (1.00-6.35 mg/kg ip) and then
placed in the chamber containing a carbon monoxide atmosphere (0.325-0.375%).
Ten to 20% of saline pretreated animals were dead at the end of the monitoring
period. Sublethal doses of KCN (3.5-6.35 mg/kg ip) produced a synergistic
lethality as compared to the saline pretreated animals. Blood was analyzed for
carbon monoxide and cyanide content to determine if there were any changes that
could explain this augmented lethality. There was no difference in carbon
monoxide or cyanide blood concentration between these treatment groups.
Nicergoline (16 mg/kg, ip) prolonged the
survival time of mice exposed to hypobaric hyoxia (165 mm Hg); nicergoline (1-16
mg/kg ip, or 16-64 mg/kg orally) also protected from a lethal dose of potassium
cyanide (3 mg/kg iv). Nicergoline (8-128 ug/kg iv) dose-dependently shortened
the duration of disappearance of spontaneous EEG in rats exposed to a sublethal
dose of KCN (1.5 mg/kg iv) and promoted the recovery from behavioral disorders
and disturbance of cerebral energy metabolism in mice exposed to a sublethal
dose of KCN. /In vitro/ Nicergoline (100 uM) protected the inhibition of mouse
brain cytochrome oxidase activity in the presence of KCN (2 uM).
Pharmacology:
Interactions:
CHLORPROMAZINE ANTAGONISM OF CYANIDE
INTOXICATION WAS POTENTIATED BY SODIUM THIOSULFATE. CHLORPROMAZINE & SODIUM
NITRITE DID NOT PROTECT AGAINST KCN LETHALITY BETTER THAN NITRITE ALONE.
To elucidate the interaction of carbon
monoxide (CO) and cyanide, the fluorescence which represents the intracellular
reduced pyridine nucleotide was measured on the rabbit kidney surface in situ.
Various doses of potassium cyanide, 2-8 umol/kg, were administered intravenously
with and without inhalation of 1, 2 and 3% carbon monoxide via a respirator. The
dose-response relationship between potassium cyanide and the fluorescence
increase fitted a salient sigmoid curve with a steep slope, and carbon monoxide
was potent to increase fluorescence independently and shifted the dose response
curve for potassium cyanide to the left. The combined effect of carbon monoxide
and potassium cyanide was of a critical dose for intracellular respiration, it
had the appearance of synergism.
Previous reports indicated that prophylactic
protection against cyanide intoxication in mice can be enhanced by
administration of chlorpromazine when it is given with sodium thiosulfate. The
mechanism of potentiation of sodium thiosulfate by chlorpromazine was studied
alone and in combination with sodium nitrite. Although chlorpromazine was found
to induce a hypothermic response, the mechanism of enhancement of the antagonism
of cyanide by chlorpromazine does not correlate with the hypothermia produced.
Various other possible mechanisms were investigated, such as rate of
methemoglobin formation, enzymatic activity of rhodanese and cytochrome oxidase,
and alpha-adrenergic blockade. The alpha-adrenergic blocking properties of
chlorpromazine may provide a basis for its antidotal effect, since this
protective effect can be reversed with an alpha-antagonist, methoxamine.
/Cyanide/
The interaction of 7 beta-adrenergic blocking
agents with salbutamol and isoproterenol was studied in the potassium cyanide
test in rats. Salbutamol (albuterol) was used at a dose that provided protection
from potassium cyanide (KCN) lethality and isoproterenol at an overdose that
failed to protect, presumably because of latent cardiotoxicity. Salbutamol-induced
protection was abolished by drugs at the following doses (sc, mg/kg); timolol
(0.0085), bunolol (0.010), propranolol (0.038), pindolol (0.15), metoprolol
(3.93), atenolol (5.69), and practolol (>10.0). Survival was restored dose
dependently in isoproterenol-overdosed rats only by atenolol (0.44), practolol
(0.51) and metoprolol (1.06). The cardioselectivity ratio (ie, salbutamol
antagonism/isoproterenol antagonism) for these 3 compounds was as follows:
practolol (>19.6), atenolol (12.9), and metoprolol (3.82).
Cysteine, a sulfur-containing amino acid, is
required to metabolize ascorbic acid (as ascorbate sulfate) and detoxify cyanide
(to thiocyanate). In guinea pigs, concomitant use of laetrile (a cyanogenic
glycoside) and ascorbic acid (in large doses) decreases the detoxification of
cyanide derived from laetrile through diminishing the availability of cysteine,
but not impairing hepatic rhodanese activity, which is involved in the
detoxification of cyanide to thiocyanate. These results agree with the symptoms
of a sublethal dose of potassium cyanide toxicity manifested by the animals.
Flunarizine is a calcium entry blocking drug
possessing antihypoxic activity in animal models of cerebral and peripheral
ischemia-anoxia and has clinical usefulness in circulatory disorders of both
central and peripheral origin. This report compares the activity of flunarizine
and verapamil, another calcium entry blocking drug, on the central nervous
system (CNS) and peripheral consequences of cytotoxic hypoxia induced by high
and low doses of KCN. The lethal effect of potassium cyanide (6 mg/kg, ip) in
rats was prevented by orally administered flunarizine (ED50= 12 mg/kg with four
hr pretreatment) but not by verapamil (at oral doses up to 80 mg/kg with one hr
pretreatment). Since the lethal effect of KCN involves failure of respiration at
the CNS level, these results suggest that flunarizine protects against the
hypoxic effect of the cyanide ion by an action in brain tissue. We found also
that the stimulant effect of low intravenous doses (0.5 mg/kg/min) of KCN upon
respiration rate was not altered in pentobarbital- and chloralose-anesthetized
rats treated with oral doses of flunarizine up to 80 mg/kg (with four hr
pretreatment). In contrast, KCN-stimulated respiration rate in pentobarbital
anesthetized rats was significantly attenuated by verapamil (20 and 40 mg/kg, po
with one hr pretreatment). Since low doses of the cyanide ion render respiration
quicker and deeper by an action on chemoreceptive cells in peripheral arteries,
the effect of verapamil against the hypoxic effect of KCN is mediated by an
action in the periphery.
The anti-anoxic effect of sufoxazine was
investigated in various cerebral anoxia models with mice, in comparison with
those of various cerebroactive drugs. Sufoxazine reduced dose-dependently the
duration of coma induced by a sublethal dose of potassium cyanide (1.8 mg/kg,
iv) significantly stimulating recovery from the coma at 5 mg/kg, ip and 30
mg/kg, po. It also protected against a lethal dose of KCN (2.5 mg/kg, iv). These
findings suggest that sufoxazine has an anti-anoxic action superior to those of
the other cerebroactive drugs used.
Cyanide intoxication in mice can be
antagonized by the opiate antagonist, (-)naloxone HCl, alone or in combination
with sodium thiosulfate and/or sodium nitrite. Potency ratios, derived from LD50
values, were compared in groups of mice pretreated with sodium nitrite (sc, 100
mg/kg), sodium thiosulfate (ip, 1 g/kg), and (-)naloxone HCl (sc, 10 mg/kg)
either alone or in various combinations. These results indicate that naloxone
HCl provides a significant protection against the lethal effects of potassium
cyanide. The protective effect of sodium thiosulfate, but not sodium nitrite,
was enhanced with (-)naloxone HCl. The combined administration of sodium nitrite
and sodium thiosulfate was further enhanced with (-)naloxone HCl. The protective
effect of naloxone HCl against the lethal effect of cyanide appears to be
restricted to the (-)stereoisomer, as the (+)stereoisomer, the inactive opiate
antagonist, is also inactive in protecting against the lethal effects of
cyanide.
Protective effects of OP-2507
(15-cis-(4-propylcyclohexyl)16,17,18,19,20-pentanor-9-deoxy-9 alpha,
6-nitrilo-PGF1 methyl ester) against cerebral anoxia and edema were investigated
in a variety of experimental models in mice and rats. OP-2507 given sc or po led
to a consistent and dose-dependent prolongation of survival time against
cerebral anoxia in hypobaric and normobaric hypoxia, potassium cyanide induced
anoxia.
Pyruvic acid, an alpha-ketocarboxylic acid,
has been shown to antagonize the lethal effects of cyanide. It is suggested that
its mechanism of action rests in its ability to react with or "bind"
cyanide. alpha-Ketoglutaric acid increased the LD50 value of cyanide (6.7 mg/kg)
by a factor of five, a value statistically equivalent to that ascertained in
mice pretreated with sodium thiosulfate and sodium nitrite. The combination of
alpha-ketoglutaric acid and sodium thiosulfate increased the LD50 value of
cyanide to 101 mg/kg. Addition of sodium nitrite to the alpha-ketoglutaric
acid/sodium thiosulfate regimen increased the LD50 value of cyanide to 119
mg/kg. Unlike sodium nitrite, no induction of methemoglobin formation was
observed with alpha-ketoglutaric acid pretreatment.
The activity of a series of 9 beta-adrenergic
agonists was studied in the potassium cyanide (5.00 mg/kg iv) and the compound
48/80 (0.50 mg/kg iv) lethality tests in rats. All compounds were active in both
tests. The ED50 values in mg/kg for protection against KCN-induced lethality
were as follows: clenbuterol (0.0047), zinterol (0.0055), hexoprenaline
(0.0093), fenoterol (0.012), isoproterenol (0.014), colterol (0.019), salbutamol
(0.028), terbutaline (0.14), and metaproterenol (0.33). By increasing the dose
levels, the protective activity of some of the compounds disappeared and LD50s
at which lethality to KCN was restored could be calculated. The protective dose
range, which is defined as the ratio of the LD50 and the ED50, greatly varies
among the test compounds. Protection from KCN induced lethality seems to be due
to an increased tissue perfusion and to occur as long as myocardial activity is
not markedly changed from normal by the test compound.
The purpose of this study was to investigate
lethality induced by low concentrations of carbon monoxide and cyanide. Male ICR
mice were used in these studies. Doses of potassium cyanide (4-9 mg/kg, ip) were
administered to animals pretreated for 3 min with either air or carbon monoxide
(0.63-0.66%). From these data the LD50 value of potassium cyanide (KCN) was
determined in these animals pretreated with either air or carbon monoxide. A
significantly lower LD50 value for KCN was found in carbon monoxide pretreated
animals as compared to air pretreated animals. In another series of experiments,
animals were pretreated with either saline or KCN (1.00-6.35 mg/kg ip) and then
placed in the chamber containing a carbon monoxide atmosphere (0.325-0.375%).
Ten to 20% of saline pretreated animals were dead at the end of the monitoring
period. Sublethal doses of KCN (3.5-6.35 mg/kg ip) produced a synergistic
lethality as compared to the saline pretreated animals. Blood was analyzed for
carbon monoxide and cyanide content to determine if there were any changes that
could explain this augmented lethality. There was no difference in carbon
monoxide or cyanide blood concentration between these treatment groups.
Nicergoline (16 mg/kg, ip) prolonged the
survival time of mice exposed to hypobaric hyoxia (165 mm Hg); nicergoline (1-16
mg/kg ip, or 16-64 mg/kg orally) also protected from a lethal dose of potassium
cyanide (3 mg/kg iv). Nicergoline (8-128 ug/kg iv) dose-dependently shortened
the duration of disappearance of spontaneous EEG in rats exposed to a sublethal
dose of KCN (1.5 mg/kg iv) and promoted the recovery from behavioral disorders
and disturbance of cerebral energy metabolism in mice exposed to a sublethal
dose of KCN. /In vitro/ Nicergoline (100 uM) protected the inhibition of mouse
brain cytochrome oxidase activity in the presence of KCN (2 uM).
Environmental Fate & Exposure:
Probable Routes of Human Exposure:
Poisoning may occur by ingestion, absorption
through injured skin or inhalation of hydrogen cyanide, liberated by action of
carbon dioxide or other acids.
... SYMPTOMS OF CHRONIC DISEASE ... REPORTED
IN ELECTROPLATERS & SILVER POLISHERS AFTER SEVERAL YEARS OF EXPOSURE.
/CYANIDES/
AMONG FUMIGATORS ... CYANIDE POISONING IS
RECOGNIZED ... /CYANIDES/
DERMATITIS ... IN WORKERS CHRONICALLY EXPOSED
TO CYANIDE SOLN. ELECTROPLATERS SUFFER FROM SUCH IRRITATION. /CYANIDE SOLN/
Body Burden:
Cyanide is present in normal healthy human
organs at concentrations ranging up to 0.5 mg/kg. /Cyanide/
Natural Pollution Sources:
In bacteria, cyanide production has been
observed in Chromobacterium violaceum and certain species of Pseudomonas.
/Cyanide/
Artificial Pollution Sources:
Material containing cyanide compounds disposed
of on land may lead to elevated levels of cyanide in underlying strata and in
groundwater. /Cyanides/
Environmental Fate:
Aquatic Fate: The alkali metal salts are very
soluble in water, and as a result, they readily dissociate into their respective
anions and cations upon release to water. The resulting cyanide ion may then
form hydrogen cyanide or react with various metals present in natural water. If
the cyanide ion is present in excess, complex metallocyanides may form; however,
if metals are prevalent, simple metal cyanides may form. /Alkali metal cyanides/
Environmental Standards & Regulations:
FIFRA Requirements:
As the federal pesticide law FIFRA directs,
EPA is conducting a comprehensive review of older pesticides to consider their
health and environmental effects and make decisions about their future use.
Under this pesticide reregistration program, EPA examines health and safety data
for pesticide active ingredients initially registered before November 1, 1984,
and determines whether they are eligible for reregistration. In addition, all
pesticides must meet the new safety standard of the Food Quality Protection Act
of 1996. Pesticides for which EPA had not issued Registration Standards prior to
the effective date of FIFRA 1988 were divided into three lists based upon their
potential for human exposure and other factors, with List B containing
pesticides of greater concern and List D pesticides of less concern. Potassium
cyanide is found on List C. Case No: 3086; Pesticide type: rodenticide; Case
Status: Reregistration Eligibility Decision Approved 9/94, PB95-173514 - OPP has
made a decision that some/all uses of the pesticide are eligible for
reregistration, as reflected in a Reregistration Eligibility Decision (RED)
document.; Active ingredient (AI): potassium cyanide; AI Status: Cancelled - The
AI is no longer contained in any registered pesticide product.
CERCLA Reportable Quantities:
Persons in charge of vessels or facilities are
required to notify the National Response Center (NRC) immediately, when there is
a release of this designated hazardous substance, in an amount equal to or
greater than its reportable quantity of 10 lb or 4.54 kg. The toll free number
of the NRC is (800) 424-8802; In the Washington D.C. metropolitan area (202)
426-2675. The rule for determining when notification is required is stated in 40
CFR 302.4 (section IV. D.3.b).
Releases of CERCLA hazardous substances are
subject to the release reporting requirement of CERCLA section 103, codified at
40 CFR part 302, in addition to the requirements of 40 CFR part 355. Potassium
cyanide is an extremely hazardous substance (EHS) subject to reporting
requirements when stored in amounts in excess of its threshold planning quantity
(TPQ) of 100 lbs.
RCRA Requirements:
P098; As stipulated in 40 CFR 261.33, when
potassium cyanide, as a commercial chemical product or manufacturing chemical
intermediate or an off-specification commercial chemical product or a
manufacturing chemical intermediate, becomes a waste, it must be managed
according to federal and/or state hazardous waste regulations. Also defined as a
hazardous waste is any container or inner liner used to hold this waste or any
residue, contaminated soil, water, or other debris resulting from the cleanup of
a spill, into water or on dry land, of this waste. Generators of small
quantities of this waste may qualify for partial exclusion from hazardous waste
regulations (40 CFR 261.5(e)).
/SRP:/ D003; A solid waste containing
potassium cyanide may become characterized as a hazardous waste when subjected
to testing for reactivity as stipulated in 40 CFR 261.23, and if so
characterized, must be managed as a hazardous waste.
Clean Water Act Requirements:
Potassium cyanide is designated as a hazardous
substance under section 311(b)(2)(A) of the Federal Water Pollution Control Act
and further regulated by the Clean Water Act Amendments of 1977 and 1978. These
regulations apply to discharges of this substance. This designation includes any
isomers and hydrates, as well as any solutions and mixtures containing this
substance.
Toxic pollutant designated pursuant to section
307(a)(1) of the Federal Water Pollution Control Act and is subject to effluent
limitations. /Cyanides/
Federal Drinking Water Guidelines:
EPA 200 ug/l /Cyanide ion/
State Drinking Water Guidelines:
(AZ) ARIZONA 220 ug/l /Cyanide ion/
(ME) MAINE 154 ug/l /Cyanide ion/
(MN) MINNESOTA 100 ug/l /Cyanide ion/
Chemical/Physical Properties:
Molecular Formula:
C-K-N
Molecular Weight:
65.11
Color/Form:
White, granular powder or fused pieces
White amorphous lumps or crystalline mass
White cubic crystals
White, granular or crystalline solid.
Odor:
Faint odor of bitter almonds
Odor of hydrogen cyanide.
Faint almond-like odor.
Melting Point:
634 deg C
Density/Specific Gravity:
1.55 at 20 deg C
pH:
11.0 (0.1 N aq soln)
Solubilities:
Sol in 2 parts cold, 1 part boiling water
Sol in 2 parts glycerol
100 g/100 cc hot water above 176 deg F
Sol in 25 parts methanol
4.55 g/100 g anhydrous liq ammonia @ -33.9 deg
C
4.91 g/100 g methanol @ 19.5 deg C
0.57 g/100 g ethanol @ 19.5 deg C
146 g/l formamide @ 25 deg C
41 g/100 g hydroxylamine @ 17.5 deg C
24.24 g/100 g glycerol of specific gravity
1.2561 @ 15.5 deg C
0.73 g/l phosphorus oxychloride soln @ 20 deg
C
0.017 g/100 g liq sulfur dioxide @ 0 deg C
0.22 g/100 g dimethylformamide @ 25 deg C
Spectral Properties:
INDEX OF REFRACTION: 1.410
Other Chemical/Physical Properties:
Deliquescent
Approximate Amount of Substance Absorbed by 1
g Charcoal: 35 mg.
Specific heat: 1.01 J/g @ 25-72 deg C; heat of
fusion: 14.7X10+3 J/mole; heat of formation: -113X10+3 J/mole (exothermic); heat
of soln: 11.7X10-3 J/mole; hydrolysis constant: 2.54X10-5 @ 25 deg C
Kh= 2.54x10-5, hydrolysis to hydrogen cyanide.
Chemical Safety & Handling:
DOT Emergency Guidelines:
Health: TOXIC; inhalation, ingestion or
contact (skin, eyes) with vapors, dusts or substance may cause severe injury,
burns, or death. Reaction with water or moist air will release toxic, corrosive
or flammable gases. Reaction with water may generate much heat which will
increase the concentration of fumes in the air. Fire will produce irritating,
corrosive and/or toxic gases. Runoff from fire control or dilution water may be
corrosive and/or toxic and cause pollution.
Fire or explosion: Non-combustible, substance
itself does not burn but may decompose upon heating to produce corrosive and/or
toxic fumes. Vapors may accumulate in confined areas (basement, tanks,
hopper/tank cars etc.). Substance will react with water (some violently),
releasing corrosive and/or toxic gases. Reaction with water may generate much
heat which will increase the concentration of fumes in the air. Contact with
metals may evolve flammable hydrogen gas. Containers may explode when heated or
contaminated with water.
Public safety: CALL Emergency Response
Telephone Number. ... Isolate spill or leak area immediately for at least 50 to
100 meters (160 to 330 feet) in all directions. Keep unauthorized personnel
away. Stay upwind. Keep out of low areas. Ventilate enclosed areas.
Protective clothing: Wear positive pressure
self-contained breathing apparatus (SCBA). Wear chemical protective clothing
which is specifically recommended by the manufacturer. Structural firefighters'
protective clothing is recommended for fire situations ONLY; it is not effective
in spill situations.
Evacuation: Spill: Fire: If tank, rail car or
tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all
directions; also, consider initial evacuation for 800 meters (1/2 mile) in all
directions.
Fire: Note: Most foams will react with the
material and release corrosive/toxic gases. Small fires: CO2 (except for
Cyanides), dry chemical, dry sand, alcohol-resistant foam. Large fires: Water
spray, fog or alcohol-resistant foam. Move containers from fire area if you can
do it without risk. Do not use straight streams. Dike fire control water for
later disposal; do not scatter the material. Fire involving tanks or car/trailer
loads: Fight fire from maximum distance or use unmanned hose holders or monitor
nozzles. Do not get water inside containers. Cool containers with flooding
quantities of water until well after fire is out. Withdraw immediately in case
of rising sound from venting safety devices or discoloration of tank. ALWAYS
stay away from the ends of tanks.
Spill or leak: ELIMINATE all ignition sources
(no smoking, flares, sparks or flames in immediate area). All equipment used
when handling the product must be grounded. Do not touch damaged containers or
spilled material unless wearing appropriate protective clothing. Stop leak if
you can do it without risk. A vapor suppressing foam may be used to reduce
vapors. DO NOT GET WATER INSIDE CONTAINERS. Use water spray to reduce vapors or
divert vapor cloud drift. Prevent entry into waterways, sewers, basements or
confined areas. Small spills: Cover with DRY earth, DRY sand, or other
non-combustible material followed with plastic sheet to minimize spreading or
contact with rain. Use clean non-sparking tools to collect material and place it
into loosely covered plastic containers for later disposal.
First aid: Move victim to fresh air. Call
emergency medical care. Apply artificial respiration if victim is not breathing.
Do not use mouth-to-mouth method if victim ingested or inhaled the substance;
induce artificial respiration with the aid of a pocket mask equipped with a
one-way valve or other proper respiratory medical device. Administer oxygen if
breathing is difficult. Remove and isolate contaminated clothing and shoes. In
case of contact with substance, immediately flush skin or eyes with running
water for at least 20 minutes. For minor skin contact, avoid spreading material
on unaffected skin. Keep victim warm and quiet. Effects of exposure (inhalation,
ingestion or skin contact) to substance may be delayed. Ensure that medical
personnel are aware of the material(s) involved, and take precautions to protect
themselves.
List of Dangerous Water-Reactive Materials:
Materials Which Create Large Amounts of Toxic (PIH) Vapor When Spilled in Water
(Dangerous From 0.5 to 10 km (0.3 to 6.0 miles) Downwind) Name of Material:
Potassium cyanide, Toxic Vapor (PIH) Produced: Hydrogen cyanide.
Fire Fighting Procedures:
Do not use carbon dioxide extinguisher.
Extinguish fire using agent suitable for surrounding fire. Water may be used on
nearby fires not involving potassium cyanide. Use water spray to keep
fire-exposed containers cool. Use alkali dry chemical.
Carbon dioxide fire extinguishers must not be
used where cyanide salts are present. /Cyanide salts/
If material involved in fire: Extinguish fire
using agent suitable for type of surrounding fire. (Material itself does not
burn or burns with difficulty.) Use water in flooding quantities as fog. Cool
all affected containers with flooding quantities of water. Use
"alcohol" foam, dry chemical, or carbon dioxide. Use water spray to
knock-down vapors. /Potassium cyanide solution/
If material involved in fire: Extinguish fire
using agent suitable for type of surrounding fire. (Material itself does not
burn or burns with difficulty.) Use foam, dry chemical, or carbon dioxide. Do
not use water on material itself. If large quantities of combustibles are
involved, use water in flooding quantities as spray and fog. Use water spray to
knock-down vapors. /Potassium cyandie, solid/
Toxic Combustion Products:
When heated to decomp it emits very toxic
fumes of cyanide & oxides of nitrogen.
Hazardous Reactivities & Incompatibilities:
Reacts with water or any acid releasing
hydrogen cyanide.
INCOMPATIBILITIES: ACIDS & ACID SYRUPS,
ALKALOIDS, CHLORAL HYDRATE, IODINE, METALLIC SALTS, PERMANGANATES, CHLORATES,
PEROXIDES
Chlorates plus potassium cyanide explode when
heated.
A mixture of /potassium cyanide and nitrites/
may cause an explosion.
Nitrogen trichloride explodes on contact with
... potassium cyanide. ...
Hydrogen cyanide and mercury (II) cyanide: The
cyanide, /mercury(II) cyanide/, is a friction- and impact-sensitive explosive
and may initiate detonation of liquid hydrogen cyanide. Other metal cyanides are
similar. /Cyanides/
Mixtures /of mercuric nitrate and potassium
cyanide/ exploded when heated, but only if contained in narrow igintion tubes.
Formation of nitrite, a more powerful oxidant than nitrate, may have been
involved.
Perchloryl fluoride /& potassium cyanide/:
Explosive reaction at 100-300 deg C.
... Reaction with ammoniacal silver
/following/ heating, shock, /or/ standing /can cause an/ explosion (formation of
silver fulminate - self-explosive). ... Heating /of potassium cyanide &/
chromium tetraoxide /can cause an/ explosion.
Cyanide may react with carbon dioxide in
ordinary air to form toxic hydrogen cyanide gas. /Cyanide/
Readily oxidized by heating to potassium
cyanate in presence of oxygen or easily reduced oxides
Fusion of mixtures of metal cyanides with
metal chlorates, perchlorates, or nitrates ... causes a violent explosion.
/Metal cyanides/
Contact with acids and acid salts causes
immediate formation of toxic and flammable hydrogen cyanide gas. ... /Cyanides/
Strong oxidizers (such as acids, acid salts,
chlorates & nitrates) [Note: Absorbs moisture from the air forming a syrup].
Hazardous Decomposition:
Potassium ... cyanide solutions give off
hydrogen cyanide when heated above 176 deg F. /Potassium cyanide soln/
Toxic gases and vapors (such as hydrogen
cyanide and carbon monoxide) may be released when cyanide decomposes. /Cyanide/
When heated to decomposition, it emits very
toxic fumes of /dipotassium oxide, hydrogen cyanide, and nitrogen oxides/.
Immediately Dangerous to Life or Health:
25 mg/cu m (as CN)
Protective Equipment & Clothing:
WHERE SKIN CAN BE EXPOSED ... PROTECTIVE
CLOTHING INCL IMPERVIOUS HAND PROTECTION SHOULD BE PROVIDED. ... WORKERS
ENTERING CONTAMINATED AREA MUST WEAR IMPERVIOUS PROTECTIVE CLOTHING AS WELL AS
... RESPIRATORY PROTECTIVE EQUIPMENT. /CYANIDES/
Respirator Selection: Less than or equal to 25
mg/cu m: (1) Filter type respirators, approved for toxic dust, with half-mask
(not applicable for calcium cyanide). (2) Chemical cartridge respirators with
replaceable cartridge for toxic dusts and acid gases; With half-mask. Maximum
service life 4 hr. Less than or equal to 50 mg/cu m: (1) Full-face gas mask,
chest or back mounted type, with industrial size canister for toxic dust and
hydrocyanic acid gas. Maximum service life 2 hr. (2) Type C supplied
air-respirator, continuous-flow or pressure-demand type (positive pressure) with
full facepiece. (3) Type A supplied-air respirator, (hose mask with blower) with
full facepiece. Greater than 50 mg/cu m: (1) Self-contained breathing apparatus
with positive pressure in full facepiece. (2) Combination supplied-air
respirator pressure-demand type with auxiliary self-contained air supply.
Emergency (no concentration limit): (1) Self-contained breathing apparatus with
positive pressure in facepiece. (2) Combination supplied-air respirator,
pressure-demand type, with auxiliary self-contained air supply. Evacuation or
Escape (no concentration limit): (1) Self-contained breathing apparatus in
demand or pressure-demand mode (negative or positive pressure). (2) Full-face
gas mask, front or back mount type with industrial size canister for toxic dust
and hydrocyanic acid gas. /Cyanide salts/
Chemical safety goggles shall be worn by
employees engaged in any operation wherein there is danger or likelihood that
dusts or solutions of cyanide salts will come into contact with the eye.
Full-length face shields with forehead protection shall be worn by employees
engaged in any operation wherein there is danger or likelihood that dusts,
molten salts, or solutions of cyanide salts may contact the face. /Cyanide
salts/
Wear ... rubber gloves ... overalls and
aprons.
Wear appropriate personal protective clothing
to prevent skin contact.
Wear appropriate eye protection to prevent eye
contact.
Eyewash fountains should be provided in areas
where there is any possibility that workers could be exposed to the substance;
this is irrespective of the recommendation involving the wearing of eye
protection.
Facilities for quickly drenching the body
should be provided within the immediate work area for emergency use where there
is a possibility of exposure. [Note: It is intended that these facilities
provide a sufficient quantity or flow of water to quickly remove the substance
from any body areas likely to be exposed. The actual determination of what
constitutes an adequate quick drench facility depends on the specific
circumstances. In certain instances, a deluge shower should be readily
available, whereas in others, the availability of water from a sink or hose
could be considered adequate.]
Recommendations for respirator selection. Max
concn for use: 25 mg/cu m. Respirator Class(es): Any supplied-air respirator.
Any self-contained breathing apparatus with a full facepiece.
Recommendations for respirator selection.
Condition: Emergency or planned entry into unknown concn or IDLH conditions:
Respirator Class(es): Any self-contained breathing apparatus that has a full
facepiece and is operated in a pressure-demand or other positive pressure mode.
Any supplied-air respirator that has a full facepiece and is operated in
pressure-demand or other positive pressure mode in combination with an auxiliary
self-contained breathing apparatus operated in pressure-demand or other positive
pressure mode.
Recommendations for respirator selection.
Condition: Escape from suddenly occurring respiratory hazards: Respirator
Class(es): Any air-purifying, full-facepiece respirator (gas mask) with a
chin-style, front- or back-mounted canister /SRP: rebreather or oxygen
generating/ providing protection against the compound of concern and having a
high-efficiency particulate filter. Any appropriate escape-type, self-contained
breathing apparatus.
Preventive Measures:
... ATTENTION TO ... VENTILATION IS NECESSARY.
... BECAUSE OF LOW PERMISSIBLE EXPOSURE LEVEL FOR HYDROGEN CYANIDE, COMPLETE
ENCLOSURE OF PROCESS IS RECOMMENDED. ... WHERE AN EXPOSURE EXISTS, WORKERS
SHOULD BE TRAINED TO RECOGNIZE THE ODOR ... & WHEN THIS IS DETECTED, THE
WORK AREA SHOULD BE EVACUATED IMMEDIATELY. /CYANIDES/
SRP: Local exhaust ventilation should be
applied wherever there is an incidence of point source emissions or dispersion
of regulated contaminants in the work area. Ventilation control of the
contaminant as close to its point of generation is both the most economical and
safest method to minimize personnel exposure to airborne contaminants.
Eyewash facilities and emergency showers shall
be provided in areas where contact with ... cyanide salts as either solids or
solutions is likely. Work clothing which has been contaminated by absorption of,
or contact with, cyanide shall be thoroughly laundered before it is worn again.
/Hydrogen cyanide and cyanide salts/
If the clothing is to be laundered or
otherwise cleaned to remove the cyanide, the person performing the operation
should be informed of cyanide's hazardous properties. /Cyanides/
Two physician's treatment kits shall be
immediately available to trained medical personnel at each plant where there is
a potential for the release of, accidental or otherwise, or for contact with,
hydrogen cyanide or cyanide salts. ... First-aid kits shall be immediately
available at workplaces where there is potential for the release, accidental or
otherwise, of hydrogen cyanide or a potential for exposure to cyanide salts. ...
Pertinent medical records shall be maintained ... /SRP: for the duraton of
employment plus 50 years [29 CFR 1910.1020]/ following the last exposure to
hydrogen cyanide or cyanide salts. /Hydrogen cyanide and cyanide salts/
PERSONS WHO WORK WITH & AROUND CYANIDE
PREPN SHOULD BE GIVEN SPECIFIC DETAILED INSTRUCTIONS ON MANAGEMENT OF CYANIDE
POISONING. /CYANIDES/
SRP: Contaminated protective clothing should
be segregated in such a manner so that there is no direct personal contact by
personnel who handle, dispose, or clean the clothing. Quality assurance to
ascertain the completeness of the cleaning procedures should be implemented
before the decontaminated protective clothing is returned for reuse by the
workers.
Food storage, preparation, and eating shall be
prohibited in areas where hydrogen cyanide is used. Smoking and the carrying of
tobacco and other smoking materials shall also be prohibited in these areas.
Clean and sanitary lunchroom facilities, if provided, must be in non-exposure
areas. ... Clothing-change and locker-room facilities shall be provided in a
non-exposure area. Workers should be encouraged to shower after work and to
change work clothing frequently. Showers and basin washing facilities shall be
located in the locker-room area. /Hydrogen cyanide or cyanide salts/
The worker should immediately wash the skin
when it becomes contaminated.
Work clothing that becomes wet or
significantly contaminated should be removed and replaced.
Workers whose clothing may have become
contaminated should change into uncontaminated clothing before leaving the work
premises.
ALL CONTAINERS ... SHOULD BE KEPT COVERED OR
IN EXHAUSTED HOOD WHEN NOT IN USE. ANY PROCESS THAT MAY RELEASE HYDROGEN CYANIDE
SHOULD BE MECHANICALLY EXHAUSTED, WITH PROVISION FOR HIGHER RATE DURING
EMERGENCIES. DIRECT READING INSTRUMENTS FOR DETERMINATION OF HYDROCYANIC ACID
ARE AVAILABLE. /CYANIDES/
Contact lenses should not be worn when working
with this chemical.
If material not involved in fire: Keep sparks,
flames, and other sources of ignition away. Keep material out of water sources
and sewers. Build dikes to contain flow as necessary. Attempt to stop leak if
without undue personnel hazard. Use water spray to knock-down vapors. /Potassium
cyanide solution/
If material not involved in fire: Keep sparks,
flames, and other sources of ignition away. Keep material out of water sources
and sewers. Use water spray to knock-down vapors. Do not use water on material
itself. /Potassium cyanide, solid/
Personnel protection: ... If contact with the
material anticipated, wear appropriate chemical protective clothing. /Potassium
cyanide, solid/
Personnel protection: Avoid breathing vapors.
Keep upwind. ... Avoid bodily contact with the material. ... Do not handle
broken packages unless wearing appropriate personal protective equipment. Wash
away any material which may have contacted the body with copious amounts of
water or soap and water. /Potassium cyanide solution; potassium cyanide, solid/
Stability/Shelf Life:
In air, it is gradually decomp on exposure to
carbon dioxide and moisture.
Shipment Methods and Regulations:
No person may /transport,/ offer or accept a
hazardous material for transportation in commerce unless that person is
registered in conformance ... and the hazardous material is properly classed,
described, packaged, marked, labeled, and in condition for shipment as required
or authorized by ... /the hazardous materials regulations (49 CFR 171-177)./
The International Air Transport Association (IATA)
Dangerous Goods Regulations are published by the IATA Dangerous Goods Board
pursuant to IATA Resolutions 618 and 619 and constitute a manual of industry
carrier regulations to be followed by all IATA Member airlines when transporting
hazardous materials.
The International Maritime Dangerous Goods
Code lays down basic principles for transporting hazardous chemicals. Detailed
recommendations for individual substances and a number of recommendations for
good practice are included in the classes dealing with such substances. A
general index of technical names has also been compiled. This index should
always be consulted when attempting to locate the appropriate procedures to be
used when shipping any substance or article.
Storage Conditions:
PROTECT FROM LIGHT.
ALL CONTAINERS OF CYANIDE SALTS SHOULD BE KEPT
COVERED OR IN EXHAUST HOOD WHEN NOT IN USE. /CYANIDES/
Store in a cool, dry, well-ventilated
location. Separate from water, acids, and carbon dioxide. Outside or detached
storage in preferred.
Cyanide salts as solids must be stored in
sealed or tightly closed containers. No hooks should be used in handling cyanide
containers. ... Storage areas must be adequately ventilated to ensure that
cyanide concentrations do not exceed the recommended workplace environmental
limits. /Cyanide salts/
Cyanide salts as solids or solutions must be
... protected from corrosion or damage. They should be stored so there is no
contact with nitrate-nitrite mixtures or peroxides. /cyanide salts/
... SHOULD BE STORED IN COOL, WELL-VENTILATED
PLACE, OUT OF DIRECT RAYS OF SUN, AWAY FROM ... FIRE HAZARD, & SHOULD BE
PERIODICALLY INSPECTED & MONITORED. INCOMPATIBLE MATERIALS SHOULD BE
ISOLATED ... /CYANIDES & COPPER CMPD/
Cleanup Methods:
Spills of cyanide salts should be immediately
and carefully cleaned up by shoveling the material into a proper container. Care
must be exercised to minimize any dispersal of cyanide dust into the air.
/Cyanide salts/
WASTE CYANIDE SALTS FROM CASE HARDENING OF
STEEL ARE DESTROYED BY REACTING THE SALTS AT 650-700 DEG C WITH WASTE FERRIC
HYDROXIDE SLUDGES FROM VARIOUS SOURCES. /CYANIDE SALTS/
REMOVAL OF COPPER, NICKEL, ZINC, CADMIUM AND
CYANIDE FROM PLATING WASTEWATER BY ELECTROFLOTATION. /CYANIDES/
Keep water away from release. Flush spill area
with hypochlorite solution. Cover in noncombustible material for proper
disposal. Shovel into suitable dry container. Control runoff and isolate
discharged material for proper disposal.
Environmental considerations - Land spill: Dig
a pit, pond, lagoon, or holding area to contain liquid or solid material. /SRP:
If time permits, pits, ponds, lagoons, soak holes, or holding areas should be
sealed with an impermeable flexible membrane liner./ Cover solids with a plastic
sheet to prevent dissolving in rain or fire fighting water. /Potassium cyanide,
solid/
Environmental considerations - Land spill: Dig
a pit, pond, lagoon, or holding area to contain liquid or solid material. /SRP:
If time permits, pits, ponds, lagoons, soak holes, or holding areas should be
sealed with an impermeable flexible membrane liner./ Dike surface flow using
soil, sand bags, foamed polyurethane, or foamed concrete. Absorb bulk liquid
with fly ash or cement powder. /Potassium cyanide solution/
Environmental considerations - Air spill:
Apply water spray or mist to knock down vapors. Vapor knock down water is
corrosive or toxic and should be diked for containment. /Potassium cyanide
solution; potassium cyanide, solid/
Environmental considerations - Water spill:
Add dilute caustic soda (sodium hydroxide). Add calcium hypochlorite ... Adjust
pH to neutral (pH= 7). /Potassium cyanide solution; potassium cyanide, solid/
Disposal Methods:
Generators of waste (equal to or greater than
100 kg/mo) containing this contaminant, EPA hazardous waste number P098; D003,
must conform with USEPA regulations in storage, transportation, treatment and
disposal of waste.
Cyanide salts should not be flushed into any
drain which may contain or subsequently receive acid waste. ... Cyanide process
waste solutions and flushings from spills should be passed through a cyanide
waste disposal system. /Cyanide salts/
Potassium cyanide is a poor candidate for
incineration.
Occupational Exposure Standards:
OSHA Standards:
Permissible Exposure Limit: Table Z-1 8-hr
Time-Weighted Avg: 5 mg/cu m. Skin Designation. /Cyanides, as CN/
Threshold Limit Values:
Ceiling limit 5 mg/cu m, skin
NIOSH Recommendations:
Recommended Exposure Limit: 10 Min Ceiling
value: 5 mg/cu m (4.7 ppm).
Immediately Dangerous to Life or Health:
25 mg/cu m (as CN)
Other Occupational Permissible Levels:
Inorganic cyanide standards: Bulgaria 0.3
mg/cu m Czechoslovakia 3-15 mg/cu m, Finland 7 mg/cu m, Federal Republic of
Germany 5 mg/cu m, Hungary 0.3 mg/cu m, Poland 0.3 mg/cu m, Romania 0.3 mg/cu m,
USSR 0.3 mg/cu m, Yugoslavia 5 mg/cu m. /Calcium, potassium, sodium, cyanide
salts/
Manufacturing/Use Information:
Major Uses:
PC Code(s): 599600, 0 labels match
ELECTROPLATING, STEEL HARDENING, EXTRACTION OF
GOLD & SILVER FROM ORES; FUMIGATION OF FRUIT TREES, SHIPS, RAILWAY CARS,
WAREHOUSES
Reagent in analytical chemistry, in
insecticide, extraction of gold and silver from ores.
Primarily for silver plating and also for dyes
& specialty products; with sodium cyanide for nitriding steel
Manufacturers:
Du Pont de Nemours & Co., Inc, Hq, 1007
Market St., Wilmington, DE 19898, (302) 774-1000; Chemicals and Pigments
Department; Production site: Memphis, TN 38127
Eagle-Picher Industries, Inc., 250 East 5th
St., Suite 500, Cincinnati, OH 45202, (513)721-7010; Production site: Lenexa, KS
66215
Hampshire Chemical Corp., 55 Hayden Ave.,
Lexington, MA 02173, (781)861-9700; Production site: Nashua, NH 03060.
Methods of Manufacturing:
Manufactured by the reaction of an aqueous
solution of potassium hydroxide with hydrogen cyanide.
Formulations/Preparations:
Grades: Commercial; Pure; Solution; Reagent
The article of commerce contains about 95% KCN.
M-44 capsules (Potassium cyanide); Pelleted/tabletted;
89.0% potassium cyanide (599600)
To prepare 99.5% /use/ high quality potassium
cyanide and potassium hydroxide.
Commercial potassium cyanide made by
neutralization or wet process ... contains 99% potassium cyanide.
Impurities:
The principal impurities are potassium
carbonate, formate, and hydroxide.
U. S. Imports:
(1984) 1.87X10+8 g
(1986) 1.47X10+6 lb
(1987) 1,468,423 lb
U. S. Exports:
(1984) 1.25X10+8 g
(1987) 32,145 lb
Laboratory Methods:
Clinical Laboratory Methods:
A FLUOROMETRIC MICRODIFFUSION METHOD IS
DESCRIBED FOR DETERMINING CYANIDE IN BIOLOGICAL FLUIDS. THIS DETECTION IS BASED
ON THE PRODUCTION OF FLUORESCENCE BY THE TREATMENT OF CN
WITH P-BENZOQUINONE DERIVATIVES. /TOTAL CYANIDE/
CYANIDE MAY BE LIBERATED FROM BIOLOGICAL
FLUIDS /BLOOD, URINE/ BY ACIDIFICATION. THE EVOLVED CYANIDE IS ABSORBED IN
ALKALI AND SODIUM CYANIDE THUS FORMED IS QUANTITATIVELY DETERMINED BY MEASURING
THE ABSORBANCE OF CHROMOPHORES FORMED BY INTERACTION OF THE CYANIDE ION WITH
SUITABLE REAGENTS ... /ANOTHER/ PROCEDURE PRESENTS A SENISITIVE GAS
CHROMATOGRAPHIC METHOD FOR DETERMINATION OF CYANIDE IN BIOLOGICAL SPECIMENS,
BASED ON ITS CONVERSION TO CYANOGEN CHLORIDE USING CHLORAMINE-T. /TOTAL CYANIDE/
A sensitive and specific radiolabel method for
measuring expired (hydrogen cyanide or carbon dioxide) derived from cyanide was
developed. An ethyl alcohol collecting solution containing 10-2M cobalt chloride
trapped 88% of the (14)hydrogen cyanide passed through the solution following
acid volatilization of a known amount of (14)potassium cyanide. The range of
linearity, r= 0.998, exceeded the 0.01-0.1 umoles tested for measuring the
pulmonary metabolites. The cobalt chloride collecting solution trapped <0.02%
of the 10-100 umoles of (14)carbon dioxide generated by acid hydrolysis of
(14)sodium bicarbonate introduction of a 2nd collecting solution specific for
carbon monoxide, composed of ethyl alcohol: ethanolamine (2:1), was used to
collect the carbon monoxide derived from cyanide. Following the sc
administration to mice of 4.6 mg/kg of potassium cyanide and 4.5 uCi
(14)potassium cyanide 1.2% and 2.3% of the dose was expired as (14)hydrogen
cyanide and (14)carbon dioxide, respectively. /Total cyanide/
GAS CHROMATOGRAPHIC DETERMINATION OF CYANIDES
IN BIOLOGICAL SPECIMENS BASED UPON ITS CONVERSION TO CYANOGEN CHLORIDE USING
CHLORAMINE-T (SODIUM P-TOLUENE SULFONCHLORAMIDE IS DESCRIBED. /TOTAL CYANIDE/
Analytic Laboratory Methods:
/DETERMINATION/ OF SODIUM & POTASSIUM
CYANIDES USING TITRIMETRIC METHOD. TITRATE WITH SILVER NITRATE.
Seven methods for the analysis of simple
cyanides have been investigated including: 1) An ion-exchange procedure; 2) A
continuous flow distillation; 3) An EDTA electrode method; 4) The AISI aeration
method; 5) An EDTA aeration method; 6) The modified Roberts-Jackson method; and
7) The EPA method for cyanides amenable to chlorination. Of all the seven
procedures studied, the modified Roberts-Jackson method is the best. It gives
complete recovery for all but one of the simple cyanides without decomposing the
complex cyanides. ... It has the unique ability to perform accurately in the
presence of both sulfide and thiocyanate. Incomplete recovery of cyanide is
found only from the mercury cyanide compounds. The addition of chloride ion
during analysis will probably overcome this deficiency. A lower limit of 2 ppb +
or - 1 ppb is possible with a precision of + or - 10% above 10 ppb. ... The
ligand-exchange procedure appears to be the most advantageous method of analysis
of total cyanides. /Total cyanides/
Color reaction: Oxidation of hemoglobin to
methemoglobin, which reacts with cyanide to form cyanomethemoglobin. This
compound has a characteristic red color and a characteristic absorption
spectrum. /Total cyanide/
Colorimetric method: Pyridine-pyrazolone.
/Total cyanide/
EPA Method 9010: Total and Amenable Cyanide
(Colorimetric, Manual) Method 9010 is used to determine the concentration of
inorganic cyanide in an aqueous waste or leachate. The method detects inorganic
cyanides that are present as either simple soluble salts or complex radicals. It
is used to determine values for both total cyanide and cyanide amenable to
chlorination; it is not intended to determine if a waste is hazardous by the
characteristic of reactivity. The cyanide, as hydrocyanic acid, is released by
refluxing the sample with strong acid and distillation of the hydrogen cyanide
into an absorber-scrubber containing sodium hydroxide solution. The cyanide ion
in the absorbing solution is then manually determined colorimetrically by
converting the cyanide to cyanogen chloride by reaction with chloramine-T at a
pH less than 8 without hydrolyzing the cyanate. ... Color is formed on addition
of the pyridine-barbituric acid reagent. In a single laboratory, using mixed
domestic and industrial waste samples at concentrations of 0.06, 0.13, 0.28, and
0.62 mg CN/l, the standard deviations were + or -
0.005, + or - 0.007, + or - 0.031, and + or - 0.094, respectively. In a single
laboratory, using mixed industrial and domestic waste samples at concentrations
of 0.28 and 0.62 mg CN/l, recoveries were 85% and 102%,
respectively. /Total and Amenable Cyanide/
Indirect atomic absorption spectrometric
analysis: (1) The complex dicyano-bis-(1,10-phenanthroline)-iron (II) is formed
and then extracted into chloroform. The chloroform is evaporated and the residue
is taken up in ethanol. The ethanol solution is aspirated directly into the
flame, and iron equivalent to a known amount of cyanide is then determined. (2)
The second method is based on precipitating silver cyanide, then determining the
excess silver ion in the supernatant by atomic absorption spectrometry. /Total
Cyanide/
REVIEW WHICH DISCUSSES THE METHODS & LIMIT
OF DETECTIONS OF CYANIDE IN NATURAL & TREATED WATERS, INDUST EFFLUENTS,
BIOLOGIC FLUIDS & SOLIDS: GAS CHROMATOGRAPHY (25 NG/ML), FLUOROMETRY (1
PPB), ION-SELECTIVE ELECTRODES (25 UG/L) & ABSORPTION SPECTROPHOTOMETRY (1-5
UG/L). /TOTAL CYANIDE/
Sampling Procedures:
AIR SAMPLES ARE USUALLY COLLECTED ON FILTERS.
Special References:
Special Reports:
NIOSH; Criteria Document: Hydrogen Cyanide and
Cyanide Salts (1976) DHEW Pub. NIOSH 77-108
USEPA/ODW; Health Advisory for: Potassium
Cyanide (Draft) (1985)
Nat'l Research Council Canada; Effects of
Cyanides on Aquatic Organisms with Emphasis Upon Fresh Water Fishes (1982) NRCC
No.19246
DHHS/ATSDR; Toxicological Profile for Cyanide
(Update) TP-92/09 (1993)
REVIEWS OF ENVIRONMENTAL EFFECTS OF
POLLUTANTS: V. CYANIDE, ORNL/EIS-81, EPA-600/1-78-027, OCTOBER 1978
USEPA; Ambient Water Quality Criteria Doc:
Cyanide (1984) EPA 440/5-84-028
Synonyms and Identifiers:
Synonyms:
AI3-28749
**PEER REVIEWED**
Caswell No 688A
**PEER REVIEWED**
CYANIDE OF POTASSIUM
**PEER REVIEWED**
CYANURE DE POTASSIUM (FRENCH)
**PEER REVIEWED**
EPA Pesticide Chemical Code 599600
**PEER REVIEWED**
HYDROCYANIC ACID, POTASSIUM SALT
**PEER REVIEWED**
Kalium cyanid (German)
**PEER REVIEWED**
M-44 capsules (Potassium cyanide)
**PEER REVIEWED**
POTASSIUM CYANIDE (K(CN))
**PEER REVIEWED**
Associated Chemicals:
Cyanide ion;57-12-5
Formulations/Preparations:
Grades: Commercial; Pure; Solution; Reagent
The article of commerce contains about 95% KCN.
M-44 capsules (Potassium cyanide); Pelleted/tabletted;
89.0% potassium cyanide (599600)
To prepare 99.5% /use/ high quality potassium
cyanide and potassium hydroxide.
Commercial potassium cyanide made by
neutralization or wet process ... contains 99% potassium cyanide.
Shipping Name/ Number DOT/UN/NA/IMO:
UN 1680; Potassium cyanide soln; potassium
cyanide, solid
IMO 6.1; Potsssium cyanide
Standard Transportation Number:
49 232 26; Potassium cyanide, solid
49 232 25; Potassium cyanide, solution
EPA Hazardous Waste Number:
P098; An acute hazardous waste when a
discarded commercial chemical product or manufacturing chemical intermediate or
an off-specification commercial chemical product or a manufacturing chemical
intermediate.
D003; /SRP:/ A waste containing potassium
cyanide may (or may not) be characterized a hazardous waste following testing
for the reactivity characteristics as prescribed by the Resource Conservation
and Recovery Act (RCRA) regulations.
RTECS Number:
NIOSH/TS8750000
Administrative Information:
Hazardous Substances Databank Number: 1245
Last Revision Date: 20020114
Last Review Date: Reviewed by SRP on 5/6/2000