HPA Compendium of Chemical Hazards Hydrogen cyanide
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HPA Compendium of Chemical Hazards
Hydrogen cyanide
Key Points
Fire
Extremely flammable
Vapour / air mixtures may be explosive
Use foam and liquid-tight protective clothing with breathing apparatus
Health
Hydrogen cyanide and its solutions may be fatal following exposure via all routes
The onset of signs and symptoms following exposure is rapid after inhalation and
ingestion
Features are mostly non-specific and include headache, nausea, dizziness and
dyspnoea
High concentrations may cause loss of consciousness, cardiac arrhythmias, coma
and death
Chronic exposure to low levels of cyanide may lead to neurological effects
Hydrogen cyanide does not have any mutagenic properties and is not considered to
be a carcinogen
Hydrogen cyanide is not considered to be a human reproductive or developmental
toxicant
Environment
Dangerous for the environment
Inform Environment Agency of substantial incidents
Prepared by J D Pritchard,
CRCE HQ, HPA
2011
Version 3Contents
GENERAL INFORMATION
Background ................................................................................................................................... 5
Frequently Asked Questions ......................................................................................................... 6
INCIDENT MANAGEMENT
Hazard Identification...................................................................................................................... 9
Standard (UK) Dangerous Goods Emergency Action Codes 9
Chemical Hazard Information and Packaging for Supply Classification 12
Globally Harmonised System of Classification and Labelling of Chemicals (GHS) 13
Physicochemical Properties ........................................................................................................ 14
Threshold Toxicity Values ........................................................................................................... 15
Published Emergency Response Guidelines .............................................................................. 16
Emergency Response Planning Guideline (ERPG) Values 16
Acute Exposure Guideline Levels (AEGLs) 16
Exposure Standards, Guidelines or Regulations......................................................................... 17
Occupational standards 17
Public health guidelines 17
Health Effects .............................................................................................................................. 18
Major routes of exposure 18
Immediate signs or symptoms of acute exposure, 18
Decontamination and First Aid .................................................................................................... 19
Dermal exposure 19
Ocular exposure 19
Inhalation 19
Ingestion 20
Further management 20
TOXICOLOGICAL OVERVIEW
Toxicological Overview................................................................................................................ 22
Summary of Health Effects 22
Kinetics and metabolism 23
Sources and routes of human exposure 23
Health Effects of Acute / Single Exposure................................................................................... 24
Human Data 24
General toxicity .............................................................................................................. 24
Contents: Page 2 of 31Inhalation ....................................................................................................................... 24
Ingestion ........................................................................................................................ 25
Dermal / ocular exposure .............................................................................................. 25
Delayed effects following an acute exposure ................................................................ 25
Animal and In-Vitro Data 26
Inhalation ....................................................................................................................... 26
Ingestion ........................................................................................................................ 26
Dermal / ocular exposure .............................................................................................. 26
Health Effects of Chronic / Repeated Exposure .......................................................................... 28
Human Data 28
General toxicity .............................................................................................................. 28
Inhalation ....................................................................................................................... 28
Genotoxicity ................................................................................................................... 28
Carcinogenicity .............................................................................................................. 28
Reproductive and developmental toxicity ...................................................................... 28
Animal and In-Vitro Data 29
Ingestion ........................................................................................................................ 29
Genotoxicity ................................................................................................................... 29
Carcinogenicity .............................................................................................................. 29
Reproductive and developmental toxicity ...................................................................... 29
References .................................................................................................................................. 30
Contents: Page 3 of 31Hydrogen cyanide
General information
Key Points
Fire
Extremely flammable
Mixtures of hydrogen cyanide vapour and air may be explosive
Use foam and liquid-tight protective clothing with breathing apparatus
Health
Exposure to hydrogen cyanide and its solutions may be fatal by all routes of exposure
The onset of signs and symptoms following exposure is rapid after inhalation and
ingestion
Features are mostly non-specific and include headache, nausea, dizziness and
difficultly breathing
High concentrations may cause loss of consciousness, abnormal heart rhythm, coma
and death
Long term exposure to low levels of cyanide may affect the nervous system
Hydrogen cyanide does not have any mutagenic properties and is not considered to
be a carcinogen
Hydrogen cyanide is not considered to be a human reproductive or developmental
toxicant
Environment
Dangerous for the environment
Inform Environment Agency of substantial incidents
Prepared by J D Pritchard
CRCE HQ, HPA
2007
Version 2HYDROGEN CYANIDE – GENERAL INFORMATION
Background
Hydrogen cyanide is a colourless or light Hydrogen cyanide is not used domestically,
blue liquid or gas and is extremely but may be given off in fires involving
flammable. It has a faint bitter almond plastics. Hydrogen Cyanide is also present
odour, though not everyone is able to detect in car exhausts fumes and cigarette smoke.
this. Other names for hydrogen cyanide
include prussic acid and hydrocyanic acid.
Hydrogen cyanide is an important industrial
chemical and over a million tonnes are
produced globally each year. It is produced
industrially by reacting methane and
ammonia in air at high temperature.
Hydrogen cyanide is poisonous and
prevents oxygen being used by the body.
Exposure to low concentrations or small
amounts may cause headaches, dizziness
and nausea; symptoms usually improve
soon after removal from an exposure. At
higher concentrations, a rapid loss of
consciousness, coma or death may occur.
There are many uses for hydrogen cyanide, People surviving a serious exposure may
primarily in the manufacture of other have long term effects from damage to the
chemicals and plastics and also as a brain.
fumigant. Cyanide compounds are used for
metal process including electroplating. Children may be more sensitive to the
Sodium cyanide is produced from hydrogen effects of hydrogen cyanide due to their
cyanide and is used to extract gold and smaller size.
silver from ores.
Hydrogen cyanide is unlikely to cause harm
Because it is widely used, exposure may to the unborn child.
occur in a number of situations.
Hydrogen cyanide is not considered to be a
Exposure may occur in the workplace cancer-causing chemical.
although safe levels allowed are enforced to
protect the employees. Such levels are
below those that are thought to cause
harmful effects.
Hydrogen cyanide is found naturally
throughout the environment at low levels as
it is released from volcanoes and certain
plants and bacteria.
General information: Page 5 of 31HYDROGEN CYANIDE – GENERAL INFORMATION
Frequently Asked Questions
What is hydrogen cyanide?
Hydrogen cyanide is a colourless or light blue extremely flammable gas or liquid which is
lighter than air.
What is hydrogen cyanide used for?
The main uses of hydrogen cyanide are in the manufacture of other chemicals to make
plastics or for use in metal processing.
How does hydrogen cyanide get into the environment?
Hydrogen cyanide is released from a number of natural processes including by bacteria and
fungi and from volcanic activity. Hydrogen cyanide may enter the environment from certain
industrial processes, from release during combustion or from accidents involving its
transport.
How will I be exposed to hydrogen cyanide?
Hydrogen cyanide is released from natural processes and so exposure will occur at very low
levels throughout the environment. As hydrogen cyanide is released from a number of
combustion processes, exposure may occur from smoke from cigarettes, fires or from car
exhaust fumes.
If there is hydrogen cyanide in the environment will I have any adverse health effects?
The presence of hydrogen cyanide in the environment does not always lead to exposure.
Clearly, in order for it to cause any adverse health effects you must come into contact with it.
You may be exposed by breathing, eating, or drinking the substance or by skin contact.
Following exposure to any chemical, the adverse health effects you may encounter depend
on several factors, including the amount to which you are exposed (dose), the way you are
exposed, the duration of exposure, the form of the chemical and if you were exposed to any
other chemicals.
Minor exposures may result in only headache, dizziness or nausea which usually cease on
removal from the exposure; long-term health effects are unlikely. Substantial exposure may
rapidly lead to unconsciousness, convulsions, coma and possibly death. If a substantial
exposure is survived, there may be long-term effects from damage to the brain.
Can hydrogen cyanide cause cancer?
Exposure to hydrogen cyanide has not been linked to the development of cancer. In other
words, hydrogen cyanide is not thought to be carcinogenic.
Does hydrogen cyanide affect children or damage the unborn child?
There is no evidence to suggest that hydrogen cyanide, at concentrations that do not affect
the mother, can affect the health of the unborn child.
General information: Page 6 of 31HYDROGEN CYANIDE – GENERAL INFORMATION
What should I do if I am exposed to hydrogen cyanide?
It is very unlikely that the general population will be exposed to a level of hydrogen cyanide
high enough to cause adverse health effects.
General information: Page 7 of 31Hydrogen cyanide
Incident management
Key Points
Fire
Extremely flammable
Incompatible or reactive with amines, oxidisers, acids, sodium hydroxide, calcium
hydroxide, sodium carbonate, water, caustics and ammonia
Emits very toxic cyanide fumes when heated to decomposition
In the event of a fire involving hydrogen cyanide, use alcohol resistant foam or fine
water spray and gas-tight protective clothing with breathing apparatus
Health
Exposure is usually by inhalation of hydrogen cyanide vapour. Hydrogen cyanide
liquid is rapidly absorbed through the skin
Exposure to high concentrations may be rapidly fatal
Environment
Dangerous to the environment
Inform Environment Agency of substantial release incidents
Prepared by J D Pritchard,
CRCE HQ, HPA
2011
Version 3HYDROGEN CYANIDE – INCIDENT MANAGEMENT
Hazard Identification
Standard (UK) Dangerous Goods Emergency Action Codes(a)
Hydrocyanic acid, aqueous solution (hydrogen cyanide,
UN 1613
aqueous solution) with not more than 20% hydrogen cyanide
Use alcohol resistant foam but, if not available, fine water
spray. Wear liquid-tight chemical protective clothing in
combination with breathing apparatus*. Spillages and
EAC 2WE decontamination run-off should be prevented from entering
drains and watercourses. Substance can be violently or
explosively reactive. There may be a public safety hazard
outside the immediate area of the incident**.
APP A(fl) Gas-tight chemical protective suit with breathing apparatus ***
Class 6.1 Toxic substance
Hazards
Sub
3 Flammable liquid
risks
Highly toxic, flammable (flash point not above 61 °C
HIN 663
inclusive)
a
Dangerous Goods Emergency Action Code List, HM Fire Service Inspectorate, Publications Section,
The Stationery Office, 2009.
Incident management: Page 9 of 31HYDROGEN CYANIDE – INCIDENT MANAGEMENT
Standard (UK) Dangerous Goods Emergency Action Codes(a)
Hydrogen cyanide, stabilised, containing less than 3 % water
UN 1614
and absorbed in a porous inert material
Use fine water spray. Wear liquid-tight chemical protective
clothing in combination with breathing apparatus*. Spillages
and decontamination run-off should be prevented from
EAC 2WE (1)
entering drains and watercourses. Substance can be
violently or explosively reactive. There may be a public safety
hazard outside the immediate area of the incident**.
APP A(fl) Gas-tight chemical protective suit with breathing apparatus ***
Class 6.1 Toxic substance
Hazards
Sub
3 Flammable liquid
risks
HIN -
Hydrogen cyanide, solution in alcohol, with not more than
UN 3294
45% hydrogen cyanide
Use alcohol resistant foam but, if not available, fine water
spray. Wear liquid-tight chemical protective clothing in
combination with breathing apparatus*. Spillages and
EAC 2WE decontamination run-off should be prevented from entering
drains and watercourses. Substance can be violently or
explosively reactive. There may be a public safety hazard
outside the immediate area of the incident**.
APP A(fl) Gas-tight chemical protective suit with breathing apparatus ***
Class 6.1 Toxic substance
Hazards
Sub
3 Flammable liquid
risks
Highly toxic, flammable (flash point not above 61 °C
HIN 663
inclusive)
a
Dangerous Goods Emergency Action Code List, HM Fire Service Inspectorate, Publications Section,
The Stationery Office, 2009.
Incident management: Page 10 of 31HYDROGEN CYANIDE – INCIDENT MANAGEMENT
Standard (UK) Dangerous Goods Emergency Action Codes(a)
Hydrogen cyanide, stabilised, containing less than 3%
UN 1051
material
Use fine water spray. Wear liquid-tight chemical protective
clothing in combination with breathing apparatus*. Spillages
and decontamination run-off should be prevented from
EAC 2WE(1)
entering drains and watercourses. Substance can be
violently or explosively reactive. There may be a public safety
hazard outside the immediate area of the incident**.
APP A(fl) Gas-tight chemical protective suit with breathing apparatus ***
Class 6.1 Toxic substance
Hazards
Sub
3 Flammable liquid
risks
HIN -
UN – United Nations number; EAC – Emergency Action Code; APP – Additional Personal
Protection; HIN - Hazard Identification Number
(1) Not applicable to the carriage of dangerous goods under Regulations Concerning the
International Carriage of Dangerous Goods by Rail (RID) and in the European Agreement
Concerning the International Carriage Dangerous Goods by Road (ADR)
* Liquid-tight clothing conforming to BS 8428 with breathing apparatus conforming to BS EN 137.
** People should stay indoors with windows and doors closed, ignition sources should be eliminated
and ventilation stopped. Non-essential personnel should move at least 250 m away from the incident.
*** Gas-tight chemical protective clothing conforming to BS EN 943 part 2 in combination with self-
contained open circuit positive pressure compressed air breathing apparatus to BS EN 137.
a
Dangerous Goods Emergency Action Code List, HM Fire Service Inspectorate, Publications Section,
The Stationery Office, 2009.
Incident management: Page 11 of 31HYDROGEN CYANIDE – INCIDENT MANAGEMENT
Chemical Hazard Information and Packaging for Supply Classification(a)
Hydrogen cyanide, hydrocyanic acid
F+ Extremely flammable
Classification T+ Very toxic
N Dangerous for the environment
R12 Extremely flammable
Risk phrases R26 Very toxic by inhalation
Very toxic to aquatic organisms, may cause long-term
R50/53
adverse effects in aquatic environment
S1/2 Keep locked up and out of the reach of children
S7/9 Keep container tightly closed and in a well ventilated place
S16 Keep away from sources of ignition – No smoking
S36/37 Wear suitable protective clothing and gloves
In case of insufficient ventilation, wear suitable respiratory
S38
Safety phrases equipment
In case of accident or if you feel unwell seek medical advice
S45
immediately (show the label where possible)
This material and its container must be disposed of as
S60
hazardous waste
Avoid release to the environment. Refer to special
S61
instructions/Safety data sheets.
a
Annex VI to Regulation (EC) No 1272/2008 on Classification, Labelling and Packaging of
Substances and Mixtures- Table 3.2.
http://esis.jrc.ec.europa.eu/index.php?PGM=cla (accessed 11/2011)
Incident management: Page 12 of 31HYDROGEN CYANIDE – INCIDENT MANAGEMENT
Globally Harmonised System of Classification and Labelling of Chemicals
)
(GHS)(a *
Hydrogen cyanide, hydrocyanic acid
Flam. Liq. 1 Flammable liquid, category 1
Acute Tox. Acute toxicity (oral, dermal, inhalation),
2* category 2
Hazard Class
and Category
Aquatic Acute hazards to the aquatic
Acute 1 environment, category 1
Aquatic Chronic hazards to the aquatic
Chronic 1 environment, category 1
H224 Extremely flammable liquid and vapour
Hazard H330 Fatal if inhaled
Statement H400 Very toxic to aquatic life
H410 Very toxic to aquatic life with long lasting effects
Signal Words DANGER
* Implemented in the EU on 20 January 2009.
a
Annex VI to Regulation (EC) No 1272/2008 on Classification, Labelling and Packaging of
Substances and Mixtures- Table 3.1.
http://esis.jrc.ec.europa.eu/index.php?PGM=cla (accessed 11/2011)
Incident management: Page 13 of 31HYDROGEN CYANIDE – INCIDENT MANAGEMENT
Physicochemical Properties
CAS number 74-90-8
Molecular weight 27
Empirical formula HCN
Common synonyms Hydrocyanic acid; Prussic acid
State at room temperature Gas
Volatility Vapour pressure = 400 mm Hg at 9.8 °C
Specific gravity Liquid: 0.7 at 20 °C (water = 1)
Vapour density Gas: 0.9 (air = 1)
Flammability Extremely flammable
Lower explosive limit 5.6%
Upper explosive limit 40%
Water solubility Miscible with water
Incompatible or reactive with amines, oxidisers, acids, sodium
Reactivity hydroxide, calcium hydroxide, sodium carbonate, water,
caustics and ammonia
Reaction or degradation
Emits very toxic cyanide fumes when heated to decomposition
products
Odour Bitter almond-like odour
Structure
References(a,b,c)
a
WHO / UN / ILO International Programme on Chemical Safety: International Chemical Safety Card
(ICSC) 0492: Hydrogen Cyanide, 2003.
b
Hydrogen Cyanide (HAZARDTEXT® Hazard Management). In: Klasco RK (Ed): TOMES® System.
Thomson Micromedex, Greenwood Village, Colorado (accessed 02/2010).
c
The Merck Index (14th Edition), Entry 4795: Hydrogen Cyanide, 2006.
Incident management: Page 14 of 31HYDROGEN CYANIDE – INCIDENT MANAGEMENT
Threshold Toxicity Values
EXPOSURE VIA INHALATION
ppm mg m-3 SIGNS AND SYMPTOMS
Difficulty breathing, rapid heart rate, paralysis,
50 55 palpitations, unconsciousness, respiratory arrest,
death
150 166 Endangering to life (30 – 60 minute exposure)
100 – 200 111 – 221 Lethal (30 – 60 minutes)
300 332 Death in minutes
Reference(a)
a
Hydrogen Cyanide (MEDITEXT® Medical Management). In: Klasco RK (Ed): TOMES® System.
Thomson Micromedex, Greenwood Village, Colorado (02/2010).
Incident management: Page 15 of 31HYDROGEN CYANIDE – INCIDENT MANAGEMENT
Published Emergency Response Guidelines
Emergency Response Planning Guideline (ERPG) Values(a)
Listed value Calculated value
(ppm) (mg m-3)
ERPG-1* N/A N/A
ERPG-2* 10 11
ERPG-3* 25 28
* Maximum airborne concentration below which it is believed that nearly all individuals could be
exposed for up to 1 hr without experiencing other than mild transient adverse health effects or
perceiving a clearly defined, objectionable odour.
** Maximum airborne concentration below which it is believed that nearly all individuals could be
exposed for up to 1 hr without experiencing or developing irreversible or other serious health effects or
symptoms which could impair an individual's ability to take protective action.
*** Maximum airborne concentration below which it is believed that nearly all individuals could be
exposed for up to 1 hr without experiencing or developing life-threatening health effects.
N/A – not appropriate
Acute Exposure Guideline Levels (AEGLs)(b)
ppm
10 min 30 min 60 min 4 hr 8 hr
AEGL-1† 2.5 2.5 2.0 1.3 1.0
AEGL-2†† 17 10 7.1 3.5 2.5
AEGL-3††† 27 21 15 8.6 6.6
†
The level of the chemical in air at or above which the general population could experience notable
discomfort.
††
The level of the chemical in air at or above which there may be irreversible or other serious long-
lasting effects or impaired ability to escape.
†††
The level of the chemical in air at or above which the general population could experience life-
threatening health effects or death.
a
American Industrial Hygiene Association (AIHA). 2010 Emergency Response Planning Guideline
Values and Workplace Environmental Exposure Level Guides Handbook, Fairfax, VA (accessed
01/2011).
b
U.S. Environmental Protection Agency. Acute Exposure Guideline Levels,
http://www.epa.gov/oppt/aegl/pubs/chemlist.htm (accessed 01/2011).
Incident management: Page 16 of 31HYDROGEN CYANIDE – INCIDENT MANAGEMENT
Exposure Standards, Guidelines or Regulations
Occupational standards
LTEL(8 hour reference period): No guideline value
specified
WEL(a)
STEL(15 min reference period): 10 ppm
(11 mg m-3)
Public health guidelines
DRINKING
50 µg L-1 (cyanide)
WATER QUALITY GUIDELINE(b)
AIR QUALITY GUIDELINE No guideline value specified
SOIL GUIDELINE VALUE AND
No guideline value specified
HEALTH CRITERIA VALUES
WEL – Workplace exposure limit; LTEL - Long-term exposure limit; STEL – Short-term
exposure limit
a
List of approved workplace exposure limits (as consolidated with amendments October 2007).
http://www.hse.gov.uk/coshh/table1.pdf (An update to EH40/2005: Workplace Exposure Limits 2005.
The Stationery Office, London) (accessed 01/2011)
b
The Water Supply (Water Quality) Regulations 2000 (England) and the Water Supply (Water Quality
Regulations 2001 (Wales) (accessed 01/2011).
Incident management: Page 17 of 31HYDROGEN CYANIDE – INCIDENT MANAGEMENT
Health Effects
Major routes of exposure(a)
Extremely toxic by ingestion, inhalation and dermal exposure.
Immediate signs or symptoms of acute exposure(b,c)
Inhalation causes headache, nausea, dyspnoea, drowsiness, dizziness, anxiety
confusion, tachycardia and palpitations. High concentrations cause hyperventilation,
brief episodes of loss of consciousness, convulsions, vomiting and hypotension. In
severe poisoning deep coma, fixed unreactive pupils, cardiovascular collapse,
respiratory depression, myocardial ischaemia, cardiac arrhythmias and pulmonary
oedema may develop. Cyanosis is often a late sign and may not occur, even in
patients with cardiovascular collapse.
There may be the characteristic "bitter almond" odour on the patient's breath (due to
excretion of hydrocyanic acid). However it is estimated that 20-40% of people are
genetically unable to detect this odour.
Inhalation: mild poisoning causes nausea, dizziness, drowsiness, hyperventilation,
anxiety. Moderate poisoning causes reduced conscious level, vomiting, convulsions,
hypotension. Severe poisoning causes coma, fixed dilated pupils, cardiovascular
collapse, respiratory failure, cyanosis.
Ingestion: mild poisoning causes nausea, dizziness, drowsiness, hyperventilation,
anxiety. Moderate poisoning causes reduced conscious level, vomiting, convulsions,
hypotension. Severe poisoning causes coma, fixed dilated pupils, cardiovascular
collapse, respiratory failure, cyanosis.
Dermal exposure may produce systemic effects.
Ocular exposure may cause irritatation the eyes. Any resultant absorption may
produce systemic effects (see below).
TOXBASE - http://www.toxbase.org (accessed 01/2011)
a
TOXBASE: Hydrogen cyanide, 12/2000.
b
TOXBASE: Cyanide – features and management, 01/2009.
c
TOXBASE: Hydrogen cyanide – medical briefing
Incident management: Page 18 of 31HYDROGEN CYANIDE – INCIDENT MANAGEMENT
Decontamination and First Aid
Important Notes
Ambulance staff, paramedics and emergency department staff treating chemically-
contaminated casualties should be equipped with the Department of Health
approved, gas-tight (Respirex) decontamination suits based on EN466:1995,
EN12941:1998 and prEN943-1:2001, where appropriate.
Decontamination should be performed using local protocols in designated areas such
as a decontamination cubicle with adequate ventilation.
Flammability warning: prevent exposure to all sources of ignition such as naked
flames, electrical equipment, oxidising chemicals and the smoking of tobacco
products.
Hydrogen cyanide is volatile and secondary contamination from exposed individuals
is unlikely.
Dermal exposure(a,b)
Remove patient from exposure.
The patient should remove all clothing and personal effects.
Double-bag soiled clothing and place in a sealed container clearly labelled as a
biohazard.
Wash hair and all contaminated skin with copious amounts of water (preferably warm)
and soap for at least 10-15 minutes. Decontaminate open wounds first and avoid
contamination of unexposed skin.
Pay special attention to skin folds, axillae, ears, fingernails, genital areas and feet.
Ocular exposure(c)
Remove patient from exposure.
Remove contact lenses if necessary and immediately irrigate the affected eye
thoroughly with water or 0.9% saline for at least 10-15 minutes.
Patients with corneal damage or those whose symptoms do not resolve rapidly
should be referred for urgent ophthalmological assessment.
Inhalation(b)
Remove patient from exposure.
Ensure a clear airway and adequate ventilation.
Give 100 % oxygen to symptomatic patients via a high flow mask with a rebreather
bag or endotracheal tube.
Monitor pulse, blood pressure, respiratory rate, oxygen saturation and cardiac
rhythm.
Correct hypotension by raising the foot of the bed and by giving an appropriate fluid
challenge. Treat brady and tachyarrhythmias appropriately.
Apply other supportive measures as indicated by the patient’s clinical condition.
TOXBASE - http://www.toxbase.org (accessed 01/2011)
a
TOXBASE: Hydrogen cyanide, 12/2000.
b
TOXBASE: Cyanide – features and management, 01/2009
c
TOXBASE: Chemicals splashed or sprayed into the eyes, 07/2007.
Incident management: Page 19 of 31HYDROGEN CYANIDE – INCIDENT MANAGEMENT
Ingestion(b)
Ensure a clear airway and adequate ventilation.
Give 100 % oxygen to symptomatic patients via a high flow mask with a rebreather
bag or endotracheal tube.
Monitor pulse, blood pressure, respiratory rate, oxygen saturation and cardiac
rhythm.
Correct hypotension by raising the foot of the bed and by giving an appropriate fluid
challenge. Treat brady and tachyarrhythmias appropriately.
Apply other supportive measures as indicated by the patient’s clinical condition.
Further management(a)
Cyanide is rapidly detoxified in the body and any casualty who is fully conscious and
breathing normally more than five minutes after removal from exposure of hydrogen
cyanide will recover spontaneously and does not require antidotal treatment.
Patients with minor symptoms only should be administered supplemental oxygen.
a
TOXBASE: Hydrogen cyanide – medical briefing, 2000.
Incident management: Page 20 of 31Hydrogen Cyanide
Toxicological overview
Key Points
Kinetics and metabolism
Hydrogen cyanide is rapidly absorbed and distributed following inhalation, oral or
dermal exposure
Cyanide ion blocks oxidative respiration causing failure of oxygen usage with tissue
hypoxia leading to metabolic acidosis
Metabolism of cyanide occurs primarily through formation of thiocyanate, which is
readily excreted in the urine
Health effects of acute exposure
Hydrogen cyanide and its solutions may be fatal following exposure via all routes
The onset of signs and symptoms following exposure is rapid after inhalation and
ingestion
Features are mostly non-specific and include headache, nausea, dizziness and
dyspnoea
High concentrations may cause loss of consciousness, cardiac arrhythmias, coma
and death
Lactic acidosis is a key feature and correlates with the severity of cyanide intoxication
Profound neurological impairment manifest as Parkinsonism may develop and may
persist on survival from severe intoxication
Health effects of chronic exposure
Long term exposure to low levels of cyanide may lead to neurological effects
Hydrogen cyanide does not have any mutagenic properties and is not considered to
be a carcinogen
Hydrogen cyanide is not considered to be a human reproductive or developmental
toxicant
Prepared by J D Pritchard
CRCE HQ, HPA
2007
Version 2HYDROGEN CYANIDE – TOXICOLOGICAL OVERVIEW
Toxicological Overview
Summary of Health Effects
Hydrogen cyanide is a potent poison and may be toxic by all routes of exposure, with rapid
onset of symptoms noted following acute exposure. Symptoms may occur within seconds
following inhalation of hydrogen cyanide vapour or minutes following ingestion of salts.
The cyanide ion blocks oxidative respiration causing tissue hypoxia; tissues with high
metabolic demands such as the CNS and cardiac are therefore key targets for toxicity.
Features of systemic toxicity include nausea, headache and dizziness; and at higher
exposures hyperventilation, a rapid loss of consciousness, cardio-respiratory depression,
coma and death. Lactate acidosis may also be noted, which improves on administration of
appropriate cyanide antidotes.
After a single, brief exposure to a low concentration of hydrogen cyanide from which an
individual recovers quickly, no long term health effects are anticipated. However, severe
intoxication following deliberate ingestion of sodium or potassium salts has been reported to
cause neurological impairments and may result in Parkinsonism. Improvements in clinical
condition have been noted with therapy, though features may persist.
Studies of workers exposed chronically to hydrogen cyanide have reported a range of non-
specific neurological effects that include headache, dizziness and paresthesiae. These
features may persist after discontinuation of exposure.
Hydrogen cyanide has no structural alerts for DNA reactivity, and studies with sodium or
potassium cyanide solutions indicate that it is not mutagenic. Hydrogen cyanide has not been
classified as a human carcinogen and there is no evidence to suggest that cyanide has
carcinogenic potential.
It is unlikely that exposure to environmental levels of hydrogen cyanide would result in
reproductive or developmental toxicity. Data from animal studies show that fetal toxicity or
embryotoxicity may occur but only at levels that cause maternal toxicity.
Toxicological overview: Page 22 of 31HYDROGEN CYANIDE – TOXICOLOGICAL OVERVIEW
Kinetics and metabolism
The cyanide ion (CN_) is the toxic moiety in hydrogen cyanide. The toxicity of simple cyanide
salts, such as potassium and sodium cyanide is, therefore, similar to that of hydrogen
cyanide [1].
The small size and moderate lipid solubility of hydrogen cyanide favours rapid absorption
across mucous membranes and uptake by the alveolar epithelium before distribution
throughout the whole body [2]. Absorption of hydrogen cyanide from the stomach is also
rapid, with the acid environment favouring the non-ionized form and facilitating absorption [2].
Cyanide absorbed from the gastrointestinal tract undergoes first pass metabolism in the liver
[1]. Ingestion of simple cyanide salts rapidly results in formation of hydrogen cyanide in the
stomach as free cyanide ion is bound to hydrogen ion in the acidic stomach environment [1].
Cyanide in solution is absorbed across intact skin due to its lipid solubility [1].
Cyanide ion toxicity is mediated primarily by its high affinity for the ferric moiety of
cytochrome c oxidase in mitochondria, a key component in oxidative respiration. This stable
but reversible interaction blocks the last stage in the electron transfer chain, resulting in
cellular hypoxia and a shift of aerobic to anaerobic cellular respiration, leading to cellular ATP
depletion, lactic acidosis and cell and tissue death [2-4].
Metabolism of cyanide ion primarily involves its conversion to soluble thiocyanate (SCN-) by
the enzyme rhodanese, with about 80% of cyanide detoxified by this route [1]. This requires
sulphane-sulphur as a co-factor i.e. one sulphur atom bonded to another sulphur atom such
as in a thiosulphate salt (e.g. sodium thiosulphate). This conversion is irreversible and the
thiocyanate ion may then be readily excreted in the urine. Cyanide is therefore unlikely to
accumulate in human tissues after chronic oral exposure [2]. Cyanide may also be
metabolised by lesser pathways including the complexing of cyanide with cobalt in
hydroxocobalamin to form cyanocobalamin (vitamin B12). Both these pathways have been
exploited in antidote therapies for cyanide poisoning [3].
While the majority of absorbed cyanide is excreted in the urine as thiocyanate, small
amounts of free cyanide may also be excreted via the lungs, sweat, urine and saliva [1]. A
plasma half life of 20 min to 1 hour has been estimated for cyanides in humans [2].
Sources and routes of human exposure
Hydrogen cyanide is released from a range of combustion process, particularly those that
involve nitrogen containing materials such as polyurethane and PVC. Mainstream smoke
from one filter cigarette contains about 100 μg of hydrogen cyanide while the amount from
non-filter cigarettes may be 5 times that amount [1]. Hydrogen cyanide intoxication is a
contributing factor to morbidity and mortality arising from smoke inhalation, together with
other toxicants such as carbon monoxide [5, 6].
Hydrogen cyanide is an important industrial reagent and is used in a number of processes.
Human exposure may therefore occur in these settings, or from accidents during storage or
transportation. Ambient levels of cyanide in the atmosphere and in drinking water are low
and are considered not to be sources of significant exposure in the UK.
The main route of human exposure to hydrogen cyanide is by inhalation, with dermal and
other routes less common.
Toxicological overview: Page 23 of 31HYDROGEN CYANIDE – TOXICOLOGICAL OVERVIEW
Health Effects of Acute / Single Exposure
Human Data
General toxicity
The clinical manifestations of acute hydrogen cyanide exposure are usually rapid in
presentation; with symptoms occurring within seconds of substantial inhalation exposure and
within minutes after ingestion of simple cyanide salts [1]. Symptoms present less rapidly after
percutaneous absorption.
The effects of cellular hypoxia are most pronounced in organs with a high ATP and oxygen
demand [4] and so early findings of exposure include non-specific CNS and cardiovascular
effects such as dizziness, headache, confusion and cardiac arrhythmias.
Metabolic acidosis is a frequent finding in cyanide toxicity which arises from blockade of
oxidative respiration. Anaerobic respiration increases to compensate with a concomitant
increase in plasma lactate levels. Plasma lactate levels may, therefore, be indicative of
cyanide toxicity [5, 7].
Changes in the arteriovenous oxygen gradient may also be noted as tissue utilisation of
oxygen is reduced [2].
Inhalation
Exposure to low concentrations may result in a range of non-specific features including
headache, dizziness, throat discomfort, chest tightness, skin itching and eye irritation and
hyperventilation [8, 9]. With more substantial exposures, features may include severe
dizziness (near syncope)[2, 9].
Exposure to a massive concentration of hydrogen cyanide gas may render an individual
unconscious within seconds [10, 11] and may lead to coma and death within minutes.
There are few data that detail hydrogen cyanide concentrations and the effects after
inhalation in humans, although some estimates of lethal concentrations have been reported
(Table 1).
Table 1. Time to death following hydrogen cyanide inhalation in humans [1]
Dose
Time to Death
mg m-3 ppm
150 135 30 min
200 180 10 min
300 270 Immediate
Values in ppm are approximate calculations from mg, where ppm = mg m-3 / gram molecular weight x 24.45
(molar volume of air at standard temperature and pressure)
Hydrogen cyanide is reported to have a characteristic odour of almonds or bitter almonds.
However, not all individuals can detect this for genetic reasons and therefore, odour is not to
be considered as a reliable indicator of exposure, or the extent of an exposure.
Toxicological overview: Page 24 of 31HYDROGEN CYANIDE – TOXICOLOGICAL OVERVIEW
Ingestion
Ingestion of hydrogen cyanide may rapidly lead to an onset of systemic toxicity including
non-specific CNS and cardio-respiratory effects. Dyspnoea and convulsions may occur early
in severe poisoning [12].
Features noted after deliberate ingestion of cyanide compounds may include nausea,
retching and collapse [13]. Patients may be unresponsive to painful stimuli and have restless,
non-purposeful movements with intermediate decorticate posturing of upper and lower
extremities [13, 14], together with severe anion gap metabolic acidosis. Improvement in the
metabolic acidosis has been noted after administration of appropriate cyanide antidotes [13].
Amounts of cyanide salts administered for suicide or with murderous intent are not usually
known so that toxic oral doses of cyanide in humans are difficult to determine. The acute
lethal oral dose for hydrogen cyanide has been reported at between 50-90 mg for hydrogen
cyanide and 200 mg for potassium or sodium cyanide (equivalent to 81 mg and 110 mg of
hydrogen cyanide, respectively) [15].
Dermal / ocular exposure
Cyanide may be absorbed across primarily uninjured skin [10] and may result in systemic
toxicity. Absorption across abraded skin may be enhanced [12].
Breathing abnormalities (including Cheyne–Stokes respiration), peripheral vasoconstriction
and plasma extravasation together with deep coma have been noted in humans after
accidents involving immersion in cisterns containing copper or potassium cyanide solutions
[2].
There is limited human data on which to assess the toxicity of hydrogen cyanide following
ocular exposure. Clearly, topical exposure to cyanide with subsequent absorption poses a
risk of systemic toxicity.
Delayed effects following an acute exposure
After a single brief exposure to a low concentration of hydrogen cyanide from which an
individual recovers quickly, no long term health effects are anticipated.
Intoxication following deliberate ingestion of sodium or potassium cyanide has been reported
to cause severe neurological impairment. Parkinsonism is widely reported; the clinical details
of which may be highly variable [14] with reported features including akinesia, rigidity,
hypersalivation and micrographia [14, 16-18]. Memory impairment has also been reported
following cyanide intoxications [13]. MRI investigations have revealed effects in the basal
ganglia including multiple areas of low signal intensity in the globus pallidus and posterior
putamen [19-21]. These findings in CNS structures with a high metabolic demand such as
basal ganglia, cerebral cortex and sensorimotor cortex [16, 18] have been attributed to both
direct toxicity of cyanide and as a consequence of cerebral hypoxia secondary to the cyanide
intoxication [22].
A slow recovery from severe dystonia syndromes arising from cyanide intoxication has been
noted in some cases and has involved treatment with Parkinsonism therapies such as
levodopa [16, 18, 19, 23].
Toxicological overview: Page 25 of 31HYDROGEN CYANIDE – TOXICOLOGICAL OVERVIEW
Animal and In-Vitro Data
Inhalation
In a study of 5 Cynomologus monkeys, incapacitation (defined in the study as semi-
consciousness and loss of muscle tone) occurred within 8-19 minutes of exposure to
100-156 ppm (110-172 mg m-3) of hydrogen cyanide [24]. Early in the exposure period
marked hyperventilation developed and was associated with an increase in EEG delta wave
activity. Respiration then slowed and a pattern of slow deep breaths with a pause at the end
of expiration between each successive breath occurred. Heart rate decreased over the
exposure period. Exposure was terminated before the full 30 min exposure period in 3/5
animals as a precautionary measure due to the severity of the signs noted. A rapid recovery
to a conscious and fairly active state was noted in the first 10 minutes of a recovery period.
Consciousness was regained in 3-7 minutes with heart rate normal within 5 min of the
recovery period starting [24]. One animal was noted to have signs of convulsions after
exposure for 28 min to 123 ppm (136 mg m-3) of hydrogen cyanide. Values in mg m-3 are
approximate calculations from ppm, where mg m-3 = ppm x gram molecular weight/24.45
(molar volume of air at standard temperature and pressure).
Maximal non-lethal concentrations in a number of species have been reported in an early
study as approximately 100 mg m-3 (dogs, rats), 140 mg m-3 (mice), 180 mg m-3 (rabbits,
monkeys, cats) and 400 mg m-3 (guinea pigs) [1].
The concentration of hydrogen cyanide inhaled markedly affects the acute toxicity and is
illustrated below in the rat (Table 2). The total dose of hydrogen cyanide leading to death is
disproportionately larger at low concentrations than at high concentrations levels;
consequently the time to death is disproportionately longer [1]. This effect has been
attributed to the proportionally greater detoxification of cyanide at the lower delivery levels
[25].
Table 2. Acute inhalation toxicity of hydrogen cyanide in rats [1, 25]
Median Lethal toxicity
Exposure
as LC50* as total dose
Duration -3
(mg m ) (min x mg m-3)
10 s 3778 631
1 min 1471 1471
5 min 493 2463
30 min 173 5070
60 min 158 9441
Ingestion
Oral LD50 values in the range 3-4 mg kg-1 have been reported in the rat (using HCN, KCN or
NaCN) and slightly lower values in the rabbit (2-3 mg kg-1) in the rabbit. Signs of toxicity
occur within minutes of dosing [1].
Dermal / ocular exposure
Dermal LD50 following application of cyanides in aqueous solutions to rabbit skin, have been
reported in the range of 7-10 mg kg-1. Toxicity is markedly greater following application to
abraded skin[1].
Toxicological overview: Page 26 of 31HYDROGEN CYANIDE – TOXICOLOGICAL OVERVIEW
Administration of sodium cyanide (1.7-5.3 mg kg-1 day-1) to the inferior conjunctival sac of
rabbits resulted in irritation, lacrimation and conjunctival hyperaemia immediately after
treatment [2].
Toxicological overview: Page 27 of 31HYDROGEN CYANIDE – TOXICOLOGICAL OVERVIEW
Health Effects of Chronic / Repeated Exposure
Human Data
General toxicity
Chronic exposure to cyanide may result in a range of non-specific neurological effects similar
to those reported following acute exposures.
Inhalation
In one study, workers exposed chronically (duration not specified) to 15 ppm hydrogen
cyanide reported a range of effects including fatigue, dizziness, headache, disturbed sleep,
tinnitus and parathesias [2]. Similar findings have been reported in another study and also
included delayed memory and/or visual impairment in around 31.5% of workers.
Concentrations of hydrogen cyanide were not, however, specified [2]. Neurological features
have been reported to persist on cessation of chronic exposure [2].
Genotoxicity
There is no in-vivo human data on which to assess the genotoxicity of hydrogen cyanide.
However, hydrogen cyanide has no structural alerts for DNA damage and taking into account
the in-vitro data, it can be concluded that hydrogen cyanide does not have significant
mutagenic potential.
Carcinogenicity
There is insufficient evidence to classify hydrogen cyanide as a carcinogen in humans and it
has not been classified by the IARC. Hydrogen cyanide is considered not to be a carcinogen.
Reproductive and developmental toxicity
There is no data that suggests that hydrogen cyanide is teratogenic in humans. There are
limited data that indicate that continued exposure to high doses of sodium cyanide may be
teratogenic, however the clinical relevance of this data is unclear; and no syndromes of
human malformation after exposure to cyanide compounds have been reported.
Cyanide ions can, however, cross the placenta and maternal exposures to high
concentrations of cyanide ion may therefore be toxic to the fetus.
Toxicological overview: Page 28 of 31HYDROGEN CYANIDE – TOXICOLOGICAL OVERVIEW
Animal and In-Vitro Data
Ingestion
There is limited data on the chronic ingestion of hydrogen cyanide. In a 2 year feeding study,
rats were provided with food fumigated with hydrogen cyanide, with customised jars used to
limit loss through volatilisation. Intakes in treated animals were 4.3 mg kg-1 day-1 and 10.8 mg
kg-1 day-1. No treatment related effects on survival or growth rate, signs of toxicity or
haematological or histopathological changes in examined organs was noted and a NOAEL of
10.8 mg kg-1 day-1 was established [1].
Genotoxicity
There are no studies on which to assess the genotoxicity of hydrogen cyanide per se.
However, the simple salt, sodium cyanide, was not mutagenic in Ames tests using S.
typhimurium strains TA100, TA1535, TA97, or TA98 with or without exogenous metabolic
activation [26]. Similarly, potassium cyanide was negative in Ames tests using S.
typhimurium strains TA1535, TA1537, TA1358, TA98 and TA100 [27].
It has been stated that the weight of evidence is that cyanide is not genotoxic [1].
Hydrogen cyanide has no structural alerts for DNA reactivity and in view of this and from the
battery of Ames tests (all negative) on its simple salts it is concluded that cyanide does not
have any significant mutagenic properties.
Carcinogenicity
No studies of the carcinogenicity of hydrogen cyanide have been conducted. Hydrogen
cyanide is not considered, however, to be a carcinogen.
Reproductive and developmental toxicity
There are no data available on the reproductive or developmental toxicity of hydrogen
cyanide.
In a study using hamsters, sodium cyanide (78.7-80.9 mg kg-1 day-1) was administered by
continuous infusion by mini-pumps on days 6-9 of gestation. A range of developmental
abnormalities were reported including neural tube defects, exencephaly, encephalocele and
malformations of the heart, limbs or tail [28]. Maternal toxicity was apparent in the majority of
dams and included weight loss, dyspnoea, in-coordination and hypothermia. Removal of the
pumps resulted in improvement and recovery of findings in the dams. The incidence of both
maternal and fetal toxicity was reduced in animals that were co-administered sodium
thiosulphate and sodium cyanide, providing support for its use in antidote regimens for
cyanide intoxication [28].
Based on limited data, it was concluded that cyanide induces developmental effects only at
doses that are overtly toxic to the mothers [1].
Toxicological overview: Page 29 of 31HYDROGEN CYANIDE – TOXICOLOGICAL OVERVIEW
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This document will be reviewed not later than 3 years or sooner if substantive evidence becomes
available.
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