This report contains the collective views of an international group of experts and does not 

necessarily represent the decisions or the stated policy of the United Nations Environment 

Programme, the International Labour Organization, or the World Health Organization. 

 

 

Concise International Chemical Assessment Document 61

 

HYDROGEN CYANIDE AND CYANIDES: 

HUMAN HEALTH ASPECTS

 

Please note that the layout and pagination of this pdf file are not identical to the 

version in press

First draft prepared by Prof. Fina Petrova Simeonova, Consultant, National Center of Hygiene, 

Medical Ecology and Nutrition, Sofia, Bulgaria; and Dr Lawrence Fishbein, Fairfax, Virginia, USA 

 

 

Published under the joint sponsorship of the United Nations Environment Programme, the 

International Labour Organization, and the World Health Organization, and produced within the 

framework of the Inter-Organization Programme for the Sound Management of Chemicals. 

 

World Health Organization 

Geneva, 2004
 The International Programme on Chemical Safety (IPCS), established in 1980, is a joint venture of 

the United Nations Environment Programme (UNEP), the International Labour Organization (ILO), and the 

World Health Organization (WHO). The overall objectives of the IPCS are to establish the scientific basis 

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following recommendations made by the 1992 UN Conference on Environment and Development to 

strengthen cooperation and increase coordination in the field of chemical safety. The purpose of the IOMC is 

to promote coordination of the policies and activities pursued by the Participating Organizations, jointly or 

separately, to achieve the sound management of chemicals in relation to human health and the environment. 

WHO Library Cataloguing-in-Publication Data 

 

Hydrogen cyanide and cyanides : human health aspects. 

 

 (Concise international chemical assessment document ; 61) 

1.Cyanides - adverse effects 2.Hydrogen cyanide - adverse effects 3.Risk assessment 

4.Environmental exposure I.International Programme on Chemical Safety II.Series 

 ISBN 92 4 153061 8 (LC/NLM Classification: QV 632) 

 ISSN 1020-6167 

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Technically and linguistically edited by Marla Sheffer, Ottawa, Canada, and printed by Wissenchaftliche 

Verlagsgesellschaft mbH, Stuttgart, Germany 
Concise International Chemical Assessment Document 61 

iii 

TABLE OF CONTENTS 

 FOREWORD ......................................................................................................................................................1 

1. EXECUTIVE SUMMARY ................................................................................................................................4 

2. IDENTITY AND PHYSICAL/CHEMICAL PROPERTIES............................................................................6 

3. ANALYTICAL METHODS ..............................................................................................................................8 

4. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE................................................................9 

 4.1 Natural occurrence...................................................................................................................................9

 4.2 Anthropogenic sources ............................................................................................................................9 

 4.2.1 Production .....................................................................................................................................9 

 4.2.2 Use.................................................................................................................................................9

 4.2.3 Release to the environment.........................................................................................................10 

5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE .......................................................................11 

 

 5.1 Environmental levels .............................................................................................................................11 

 5.1.1 Air................................................................................................................................................11 

5.1.2 Water ...........................................................................................................................................12 

5.1.3 Soil ..............................................................................................................................................12 

5.1.4 Food.............................................................................................................................................12 

5.1.5 Other............................................................................................................................................13 

 5.2 Human exposure ....................................................................................................................................13 

 5.2.1 General population......................................................................................................................13 

 5.2.2 Occupational exposure................................................................................................................14 

6. COMPARATIVE KINETICS AND METABOLISM IN LABORATORY ANIMALS AND 

 HUMANS .........................................................................................................................................................14

 

 6.1 Absorption..............................................................................................................................................14 

 6.2 Distribution ............................................................................................................................................15

 6.3 Metabolism and excretion......................................................................................................................15 

 6.4 Biological monitoring............................................................................................................................17 

7. EFFECTS ON LABORATORY MAMMALS AND IN VITRO TEST SYSTEMS ......................................17 

 7.1 Single exposure......................................................................................................................................17 

 7.2 Short-term exposure...............................................................................................................................19 

 7.2.1 Oral..............................................................................................................................................19

 7.2.2 Inhalation ....................................................................................................................................19 

 7.2.2.1 Hydrogen cyanide ........................................................................................................19 

 7.2.2.2 Acetone cyanohydrin ...................................................................................................19 

 7.3 Medium-term exposure..........................................................................................................................19 

 7.3.1 Oral..............................................................................................................................................19

 7.3.2 Inhalation ....................................................................................................................................21 

 7.3.2.1 Cyanogen......................................................................................................................21 

 7.3.2.2 Acetone cyanohydrin ...................................................................................................21 

 7.4 Long-term exposure...............................................................................................................................22 

 7.5 Genotoxicity and related end-points......................................................................................................22 

 7.6 Reproductive and developmental toxicity.............................................................................................23 
iv

 7.6.1 Effects on fertility .......................................................................................................................23 

 7.6.2 Developmental toxicity...............................................................................................................23 

 7.7 Neurotoxicity .........................................................................................................................................24

 7.8 Irritation and sensitization .....................................................................................................................25 

 7.9 Mode of action .......................................................................................................................................25 

8. EFFECTS ON HUMANS ................................................................................................................................25 

 8.1 General population.................................................................................................................................25 

 8.1.1 Exposure to cyanides ..................................................................................................................25 

 8.1.2 Food containing cyanogenic glycosides.....................................................................................27 

 8.2 Occupational exposure...........................................................................................................................28 

9. HEALTH EFFECTS EVALUATION .............................................................................................................30 

 9.1 Hazard identification and dose–response assessment...........................................................................30 

 9.2 Criteria for setting tolerable intakes/concentrations for cyanides ........................................................31 

 9.3 Sample risk characterization..................................................................................................................32 

 9.4 Uncertainties in the hazard characterization .........................................................................................32 

10. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES.................................................................32 

REFERENCES.........................................................................................................................................................33 

APPENDIX 1 — SOURCE DOCUMENTS...........................................................................................................41 

APPENDIX 2 — CICAD PEER REVIEW.............................................................................................................42 

APPENDIX 3 — 10TH FINAL REVIEW BOARD ..............................................................................................43 

APPENDIX 4 — 11TH FINAL REVIEW BOARD ..............................................................................................44 

APPENDIX 5 — ABBREVIATIONS AND ACRONYMS ..................................................................................45 

INTERNATIONAL CHEMICAL SAFETY CARDS ............................................................................................46 

RÉSUMÉ D’ORIENTATION.................................................................................................................................62 

RESUMEN DE ORIENTACIÓN............................................................................................................................65
Hydrogen cyanide and cyanides: Human health aspects 

1 

FOREWORD

 Concise International Chemical Assessment 

Documents (CICADs) are the latest in a family of 

publications from the International Programme on 

Chemical Safety (IPCS) — a cooperative programme of 

the World Health Organization (WHO), the International 

Labour Organization (ILO), and the United Nations 

Environment Programme (UNEP). CICADs join the 

Environmental Health Criteria documents (EHCs) as 

authoritative documents on the risk assessment of 

chemicals. 

 International Chemical Safety Cards on the relevant 

chemical(s) are attached at the end of the CICAD, to 

provide the reader with concise information on the 

protection of human health and on emergency action. 

They are produced in a separate peer-reviewed 

procedure at IPCS. They may be complemented by 

information from IPCS Poison Information Monographs 

(PIM), similarly produced separately from the CICAD 

process. 

 CICADs are concise documents that provide summaries of the relevant scientific information concerning 

the potential effects of chemicals upon human health 

and/or the environment. They are usually based on 

selected national or regional evaluation documents or on 

existing EHCs. Before acceptance for publication as 

CICADs by IPCS, these documents undergo extensive 

peer review by internationally selected experts to ensure 

their completeness, accuracy in the way in which the 

original data are represented, and the validity of the 

conclusions drawn. 

 The primary objective of CICADs is characterization of hazard and dose–response from exposure to a 

chemical. CICADs are not a summary of all available 

data on a particular chemical; rather, they include only 

that information considered critical for characterization 

of the risk posed by the chemical. The critical studies 

are, however, presented in sufficient detail to support the 

conclusions drawn. For additional information, the 

reader should consult the identified source documents 

upon which the CICAD has been based. 

 Risks to human health and the environment will 

vary considerably depending upon the type and extent of 

exposure. Responsible authorities are strongly encouraged to characterize risk on the basis of locally measured 

or predicted exposure scenarios. To assist the reader, 

examples of exposure estimation and risk characterization are provided in CICADs, whenever possible. These 

examples cannot be considered as representing all 

possible exposure situations, but are provided as 

guidance only. The reader is referred to EHC 170.1

 While every effort is made to ensure that CICADs 

represent the current status of knowledge, new information is being developed constantly. Unless otherwise 

stated, CICADs are based on a search of the scientific 

literature to the date shown in the executive summary. In 

the event that a reader becomes aware of new information that would change the conclusions drawn in a 

CICAD, the reader is requested to contact IPCS to 

inform it of the new information. 

Procedures

 The flow chart on page 2 shows the procedures 

followed to produce a CICAD. These procedures are 

designed to take advantage of the expertise that exists 

around the world — expertise that is required to produce 

the high-quality evaluations of toxicological, exposure, 

and other data that are necessary for assessing risks to 

human health and/or the environment. The IPCS Risk 

Assessment Steering Group advises the Coordinator, 

IPCS, on the selection of chemicals for an IPCS risk 

assessment based on the following criteria:

• there is the probability of exposure; and/or 

• there is significant toxicity/ecotoxicity. 

Thus, it is typical of a priority chemical that 

• it is of transboundary concern; 

• it is of concern to a range of countries (developed, 

developing, and those with economies in transition) 

for possible risk management; 

• there is significant international trade; 

• it has high production volume; 

• it has dispersive use. 

The Steering Group will also advise IPCS on the appropriate form of the document (i.e., a standard CICAD or a 

de novo CICAD) and which institution bears the responsibility of the document production, as well as on the 

type and extent of the international peer review. 

The first draft is usually based on an existing 

national, regional, or international review. When no 

appropriate source document is available, a CICAD may 

be produced de novo. Authors of the first draft are 

usually, but not necessarily, from the institution that 

developed the original review. A standard outline has 

been developed to encourage consistency in form. The 

 

1 International Programme on Chemical Safety (1994) 

Assessing human health risks of chemicals: derivation of 

guidance values for health-based exposure limits. Geneva, 

World Health Organization (Environmental Health Criteria 

170) (also available at http://www.who.int/pcs/).
Concise International Chemical Assessment Document 61

 CICAD PREPARATION FLOW CHART 

Selection of priority 

chemical, author 

institution, and agreement 

on CICAD format

Preparation of first draft 

Primary acceptance 

review by IPCS and 

revisions as necessary 

Selection of review 

process 

Peer review 

Review of the comments 

and revision of the 

document 

Final Review Board:

Verification of revisions 

due to peer review 

comments, revision, and 

approval of the document 

Editing 

Approval by Coordinator, 

IPCS

Publication of CICAD on 

web and as printed text

Advice from Risk Assessment 

Steering Group

Criteria of priority: 

• there is the probability of exposure; and/or

• there is significant toxicity/ecotoxicity. 

Thus, it is typical of a priority chemical that 

• it is of transboundary concern; 

• it is of concern to a range of countries 

(developed, developing, and those with 

economies in transition) for possible risk

management; 

• there is significant international trade;

• the production volume is high;

• the use is dispersive. 

Special emphasis is placed on avoiding 

duplication of effort by WHO and other 

international organizations. 

A usual prerequisite of the production of a 

CICAD is the availability of a recent highquality national/regional risk assessment

document = source document. The source 

document and the CICAD may be produced in 

parallel. If the source document does not 

contain an environmental section, this may be

produced de novo, provided it is not 

controversial. If no source document is 

available, IPCS may produce a de novo risk 

assessment document if the cost is justified. 

Depending on the complexity and extent of

controversy of the issues involved, the steering 

group may advise on different levels of peer 

review: 

• standard IPCS Contact Points

• above + specialized experts 

• above + consultative group 

2 
Hydrogen cyanide and cyanides: Human health aspects 

3 

first draft undergoes primary review by IPCS to ensure 

that it meets the specified criteria for CICADs. 

 The second stage involves international peer review 

by scientists known for their particular expertise and by 

scientists selected from an international roster compiled 

by IPCS through recommendations from IPCS national 

Contact Points and from IPCS Participating Institutions. 

Adequate time is allowed for the selected experts to 

undertake a thorough review. Authors are required to 

take reviewers’ comments into account and revise their 

draft, if necessary. The resulting second draft is 

submitted to a Final Review Board together with the 

reviewers’ comments. At any stage in the international 

review process, a consultative group may be necessary 

to address specific areas of the science. When a CICAD 

is prepared de novo, a consultative group is normally 

convened. 

 The CICAD Final Review Board has several 

important functions:

• to ensure that each CICAD has been subjected to an 

appropriate and thorough peer review; 

• to verify that the peer reviewers’ comments have 

been addressed appropriately; 

• to provide guidance to those responsible for the 

preparation of CICADs on how to resolve any 

remaining issues if, in the opinion of the Board, the 

author has not adequately addressed all comments 

of the reviewers; and 

• to approve CICADs as international assessments. 

Board members serve in their personal capacity, not as 

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industry. They are selected because of their expertise in 

human and environmental toxicology or because of their 

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chosen according to the range of expertise required for a 

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 Board members, authors, reviewers, consultants, 

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discussion at any stage of the process. Representatives 

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observe the proceedings of the Final Review Board. 

Observers may participate in Board discussions only at 

the invitation of the Chairperson, and they may not 

participate in the final decision-making process.
Concise International Chemical Assessment Document 61 

4 

1. EXECUTIVE SUMMARY 

This CICAD on hydrogen cyanide and cyanides 

(human health aspects) was prepared by Prof. Fina 

Petrova Simeonova and Dr Lawrence Fishbein, based 

principally on the Agency for Toxic Substances and 

Disease Registry toxicological profile for cyanide 

(ATSDR, 1997) and the Joint FAO/WHO Expert 

Committee on Food Additives document on cyanogenic 

glycosides (JECFA, 1993). The source documents and a 

description of their review processes are presented in 

Appendix 1. A comprehensive literature search of 

several online databases was performed in October 2002 

to identify any relevant references published subsequent 

to those cited in the source documents. This CICAD was 

first discussed at the 10th Final Review Board meeting, 

held in Monks Wood, United Kingdom, on 16–19 

September 2002. Following revision, it was discussed 

again and approved as an international assessment at the 

11th Final Review Board meeting, held in Varna, 

Bulgaria, on 8–11 September 2003. Participants at the 

10th and 11th Final Review Board meetings are listed in 

Appendices 2 and 3. The drafts discussed at these 

meetings were peer reviewed before the meetings; 

information on the peer review process is presented in 

Appendix 4. The International Chemical Safety Cards on 

hydrogen cyanide, sodium cyanide, potassium cyanide, 

calcium cyanide, cyanogen, cyanogen chloride, acetone 

cyanohydrin, and potassium ferricyanide, produced by 

the International Programme on Chemical Safety (IPCS, 

1999a,b, 2000b, 2001, 2002a,b,c,d), have also been 

reproduced in this document. 

 Cyanides comprise a wide range of compounds of 

varying degrees of chemical complexity, all of which 

contain a CN moiety, to which humans are exposed in 

gas, liquid, and solid form from a broad range of natural 

and anthropogenic sources. While many chemical forms 

of cyanide are used in industrial application or are 

present in the environment, the cyanide anion CN–

 is the 

primary toxic agent, regardless of origin. 

 Hydrogen cyanide is a colourless or pale blue liquid 

or gas with a faint bitter almond-like odour. Hydrogen 

cyanide is used primarily in the production of substances 

such as adiponitrile, methyl methacrylate, chelating 

agents, cyanuric chloride, methionine and its hydroxylated analogues, and sodium and potassium cyanide. 

Hydrogen cyanide is also used as a fumigant in ships, 

railroad cars, large buildings, grain silos, and flour mills, 

as well as in the fumigation of peas and seeds in vacuum 

chambers.

 Other cyanides, such as sodium and potassium 

cyanide, are solid or crystalline hygroscopic salts widely 

used in ore extracting processes for the recovery of gold 

and silver, electroplating, case-hardening of steel, base 

metal flotation, metal degreasing, dyeing, printing, and 

photography. They are also widely used in the synthesis 

of organic and inorganic chemicals (e.g., nitriles, 

carboxylic acids, amides, esters, and amines; heavy 

metal cyanides) and in the production of chelating 

agents. 

 Anthropogenic sources of cyanide release to the 

environment are diverse. Releases to air include chemical manufacturing and processing industries, such as 

metallurgical industries and metal plating, and extraction 

of gold and silver from low-grade ores. Other sources 

include volatilization from cyanide wastes disposed of in 

landfills and waste ponds, emissions from municipal 

solid waste incinerators, biomass burning, fossil fuel 

combustion, including vehicle emissions, fumigation 

operations, and the production of coke or other coal 

carbonization procedures. 

 Hydrogen cyanide is formed during the incomplete 

combustion of nitrogen-containing polymers, such as 

certain plastics, polyurethanes, and wool. Hydrogen 

cyanide is present in cigarette smoke.

 Non-point sources of cyanide released to water can 

result from runoff from cyanide-containing anti-caking 

salts used on roads, migration from landfills, and agricultural and atmospheric fallout and washout. Point 

sources of releases to water include discharges from gold 

mining plants, wastewater treatment works, iron and 

steel production, and organic chemical industries. 

 Principal natural sources of cyanides are over 

2000 plant species, including fruits and vegetables, 

that contain cyanogenic glycosides, which can release 

cyanide on hydrolysis when ingested. Among them, 

cassava (tapioca, manioc) and sorghum are staple foods 

for hundreds of millions of people in many tropical 

countries. Known cyanogenic glycosides in plants 

include amygdalin, linamarin, prunasin, dhurrin, 

lotaustralin, and taxiphyllin. Hydrogen cyanide is 

released into the atmosphere from natural biogenic 

processes from higher plants, bacteria, and fungi. 

 In air, cyanide is present as gaseous hydrogen 

cyanide, with a small amount present in fine dust 

particles. Cyanides have the potential to be transported 

over long distances from their respective emission 

sources. 

 The majority of the population is exposed to very 

low levels of cyanide in the general environment. There 

are, however, specific subgroups with higher potential 

for exposure. These include individuals involved in 

large-scale processing of cassava and those consuming 

significant quantities of improperly prepared foods 

containing cyanogenic glycosides, such as cassava, 
Hydrogen cyanide and cyanides: Human health aspects 

5 

speciality foods such as apricot pits, and bitter almonds. 

Other subgroups with greatest potential for exposure 

include those in the vicinity of accidental or intended 

releases from point sources, active and passive smokers, 

and fire-related smoke inhalation victims. 

 Workers may be exposed to cyanides during fumigation operations and the production and use of cyanides 

in many industrial processes — for example, electroplating, case-hardening of steel, and extraction of gold 

and silver from ores. 

 Cyanides are well absorbed via the gastrointestinal 

tract or skin and rapidly absorbed via the respiratory 

tract. Once absorbed, cyanide is rapidly and ubiquitously 

distributed throughout the body, although the highest 

levels are typically found in the liver, lungs, blood, and 

brain. There is no accumulation of cyanide in the blood 

or tissues following chronic or repeated exposure. 

 Approximately 80% of absorbed cyanide is metabolized to thiocyanate in the liver by the mitochondrial 

sulfur transferase enzyme rhodanese and other sulfur 

transferases. Thiocyanate is excreted in the urine. Minor 

pathways for cyanide detoxification involve reaction 

with cystine to produce aminothiazoline- and iminothiazolidinecarboxylic acids and combination with hydroxycobalamin (vitamin B12a) to form cyanocobalamin 

(vitamin B12); these end-products are also excreted in the 

urine. 

 The principal features of the toxicity profile for 

cyanide are its high acute toxicity by all routes of administration, with a very steep and rate-dependent dose–

effect curve, and chronic toxicity, probably mediated 

through the main metabolite and detoxification product, 

thiocyanate. The toxic effects of cyanide ion in humans 

and animals are generally similar and are believed to 

result from inactivation of cytochrome oxidase and 

inhibition of cellular respiration and consequent histotoxic anoxia. The primary targets of cyanide toxicity in 

humans and animals are the cardiovascular, respiratory, 

and central nervous systems. The endocrine system is 

also a potential target for long-term toxicity, as a function of continued exposure to thiocyanate, which prevents the uptake of iodine in the thyroid and acts as a 

goitrogenic agent. 

 In humans, whereas slight effects occur at exposure 

levels of 20–40 mg/m3

, 50–60 mg/m3 can be tolerated 

without immediate or late effects for 20 min to 1 h, 120–

150 mg/m3

 may lead to death after 0.5–1 h, 150 mg/m3

is likely to be fatal within 30 min, 200 mg/m3

 is likely 

fatal after 10 min, and 300 mg/m3

 is immediately fatal. 

The lowest reported oral lethal dose for humans is 

0.54 mg/kg body weight, and the average absorbed dose 

at the time of death has been estimated at 1.4 mg/kg 

body weight (calculated as hydrogen cyanide). Sequelae 

after severe acute intoxications may include neuropsychiatric manifestations and Parkinson-type disease. 

Cyanide from tobacco smoke has been implicated as a 

contributing factor in tobacco–alcohol amblyopia. Longterm exposure to lower concentrations of cyanide in 

occupational settings can result in a variety of symptoms 

related to central nervous system effects. 

 Long-term consumption of cassava containing high 

levels of cyanogenic glycosides has been associated with 

tropical ataxic neuropathy, spastic paraparesis, and, in 

areas with low iodine intake, development of hypothyroidism, goitre, and cretinism. While exposure to 

cyanide has been crudely estimated to be 15–50 mg/day 

in endemic areas in some such cases, owing to the 

limitations of data on exposure and potential impact of 

confounders such as malnutrition, low protein content of 

the diet, vitamin deficiencies, and iodine status, the 

available data do not provide meaningful information on 

dose–response for cyanide. 

 Data on end-points other than acute toxicity are 

somewhat limited. This is attributable in large part to 

difficulties in conducting, for example, investigations of 

repeated-dose or chronic toxicity due to the high acute 

toxicity of the compound. Cyanides are weakly irritating 

to the skin and eye; data on sensitizing properties or 

carcinogenicity of hydrogen cyanide or its alkali salts 

have not been identified. Although somewhat limited, 

the weight of evidence of available data indicates that 

cyanide is not genotoxic and that it induces developmental effects only at doses or concentrations that are 

overtly toxic to the mothers. 

 Available data in human populations are considered 

inadequate as a basis for characterization of dose–

response for chronic ingestion of cyanide. In a 13-week 

repeated-dose toxicity study in which cyanide was 

administered in drinking-water, there were no clinical 

signs associated with central nervous system effects or 

histopathological effects in the brain or thyroid of rats or 

mice exposed to doses up to 12.5 mg and 26 mg cyanide/kg body weight per day, respectively. At 12.5 mg 

cyanide/kg body weight per day, there were slight 

changes in the reproductive tract in male rats, which, 

although they apparently would not affect fertility in 

rats, are possibly significant to humans. The noobserved-adverse-effect level (NOAEL) for these effects 

was 4.5 mg/kg body weight per day. The examination of 

neurotoxicity in this study was limited to clinical observation and optical microscopy in autopsy. The few available studies specifically intended to investigate neurotoxicity, while reporting adverse effects at exposure 

levels of 1.2 mg cyanide/kg body weight per day in rats 

and 0.48 mg cyanide/kg body weight per day in goats, 

suffer from weaknesses that preclude their quantitative 

assessment. 
Concise International Chemical Assessment Document 61 

6 

 In relation to characterization of concentration–

response for repeated-dose toxicity for inhalation 

(relevant principally to the occupational environment), 

in three separate studies in rats, there were no adverse 

systemic effects in rats exposed to acetone cyanohydrin, 

which is rapidly hydrolysed to hydrogen cyanide at 

physiological pH, at concentrations up to 211 mg/m3

(corresponding to a concentration of 67 mg hydrogen 

cyanide/m3

). The steepness of the dose–effect curve is 

illustrated by the observation of 30% mortality among 

rats exposed part of the day to 225 mg acetone cyanohydrin/m3

 (71 mg hydrogen cyanide/m3). 

 Adverse effects of exposure to the low concentrations of cyanide that are generally present in the general 

environment (<1 μg/m3

 in ambient air; <10 μg/litre in 

water) are unlikely. Acute cyanide intoxications may 

arise from eating apricot kernels, choke cherries, and 

other stone fruit kernels with high concentrations of 

cyanogenic glycosides. Inadequately prepared cassava, 

when constituting the major part of the diet, may be 

hazardous.

2. IDENTITY AND PHYSICAL/CHEMICAL 

PROPERTIES 

 Hydrogen cyanide (HCN) is a colourless or pale 

blue liquid or gas with a faint bitter almond-like odour. 

Common synonyms are hydrocyanic acid and prussic 

acid. Hydrogen cyanide is a very weak acid, with a pKa

value of 9.22 at 25 °C. It is soluble in water and alcohol. 

Hydrogen cyanide is commercially available as a gas or 

as a technical-grade liquid in concentrations of 5, 10, 

and 96–99.5%. Phosphoric acid is added to liquid 

hydrogen cyanide as a stabilizer to prevent decomposition and explosion (ATSDR, 1997). Some important 

physical and chemical properties of hydrogen cyanide 

are summarized in Table 1. 

The conversion factors1

 for hydrogen cyanide in air 

(at 20 °C and 101.3 kPa) are as follows: 

1 ppm = 1.12 mg/m3

1 mg/m3

 = 0.890 ppm

 

1 In keeping with WHO policy, which is to provide measurements in SI units, all concentrations of gaseous chemicals in air 

will be given in SI units in the CICAD series. Where the 

original study or source document has provided concentrations 

in SI units, these will be cited here. Where the original study or 

source document has provided concentrations in volumetric 

units, conversions will be done using the conversion factors 

given here, assuming a temperature of 20 °C and a pressure of 

101.3 kPa. Conversions are to no more than two significant 

digits.

Table 1: Physical and chemical properties of hydrogen 

cyanide (CAS No. 74-90-8).a 

Property Value 

Relative molecular mass 27.03 

Boiling point (°C) 25.70 

Solubility (30 °C) Miscible with water; 

soluble in ethanol 

Specific density: vapours (31 °C) 0.937 

Odour threshold 0.7 mg/m3

 in air 

0.17 mg/litre in water 

Henry’s law constant 

(dimensionless) 

180–300b

 

Octanol/water partition coefficient 

(log Kow) 

0.66 

Vapour pressure (kPa) 35.2 at 0 °C 

107.2 at 27.2 °C 

a From ACGIH (2001); DECOS (2002). b

 Hine & Weimar (1965); Edwards et al. (1978); Gaffney et al. 

(1987).

 Sodium cyanide (NaCN) is a white hygroscopic 

crystalline powder with a faint bitter almond-like odour. 

Common synonyms are cyanide of sodium and hydrocyanic acid, sodium. Commercially available sodium 

cyanide generally achieves a purity of 95–98%. The 

aqueous solution of sodium cyanide is strongly alkaline 

and rapidly decomposes. Sodium cyanide produces 

hydrogen cyanide on contact with acids or acid salts. 

 Potassium cyanide (KCN) is a white deliquescent 

solid with an odour of hydrogen cyanide. Common 

synonyms are hydrocyanic acid, potassium salt and 

cyanide of potassium. Potassium cyanide is commercially available at a 95% purity. An aqueous solution of 

potassium cyanide in water is strongly alkaline. Potassium cyanide also produces hydrogen cyanide on contact 

with acids or acid salts. 

 Calcium cyanide (Ca(CN)2), also commonly called 

cyanide of calcium, calcid, or calsyan, is a white crystalline solid. Its aqueous solution gradually liberates 

hydrogen cyanide. Cyanides such as sodium cyanide, 

potassium cyanide, and calcium cyanide form strong 

complexes with many metals (Table 2). 

 Cyanogen is a colourless toxic gas with an almondlike odour. Common synonyms are carbon nitrile, 

dicyanogen, ethane dinitrile, and oxalic acid dinitrile. 

Cyanogen is slowly hydrolysed in aqueous solution, 

yielding oxalic acid and ammonia. The conversion factors for cyanogen in air at 20 °C and 101.3 kPa are as 

follows: 

 1 ppm = 2.16 mg/m3

1 mg/m3 = 0.462 ppm
Hydrogen cyanide and cyanides: Human health aspects 

7 

Table 2: Physical and chemical properties of selected cyanide compounds.a 

Species 

CAS 

number 

Molecular 

formula 

Relative 

molecular 

mass Common synonym(s) 

Boiling 

point 

(°C) Solubility 

Sodium 

cyanide 

143-33-9 NaCN 49.02 Cyanide of sodium Soluble in water, slightly 

soluble in alcohol 

Potassium 

cyanide 

151-50-8 KCN 65.11 Cyanide of potassium Soluble in water, slightly 

soluble in alcohol 

Calcium 

cyanide 

592-01-8 Ca(CN)2 92.12 Calcid; calsyan Soluble in water, slightly 

soluble in alcohol 

Copper 

cyanide 

54-92-3 CuCN 89.56 Cupricin Insoluble in water 

Potassium 

silver cyanide 

501-61-6 KAg(CN)2 198.01 Potassium 

dicyanoargentate 

 Soluble in water, slightly 

soluble in ether 

Sodium 

ferrocyanide 

13601-19-9 Na4Fe(CN)6 303.91 Sodium 

hexacyanoferrate (II) 

 Soluble in water 

Potassium 

ferrocyanide 

13943-57-3 K4Fe(CN)6 368.35 Yellow prussiate of 

potash 

 Soluble in water 

Potassium 

ferricyanide 

13746-66-2 K3Fe(CN)6 329.95 Red prussiate of 

potash 

 Slowly soluble in 2.5 

parts of cold water; 

decomposes slowly in 

water 

Cyanogen 460-19-5 NCCN 52.04 Carbon nitrile; 

dicyanogen 

–20.7 Soluble in water, 

alcohol, and ether 

Cyanogen 

chloride 

506-77-4 CNCl 61.47 Chlorine cyanide 13.8 Soluble in water and 

alcohol 

Acetone 

cyanohydrin 

75-86-5 (CH3)2C(OH)CN 85.10 ACH; methyllactonitrile 82 Soluble in water 

Sodium 

nitroprusside 

14402-89-2 Na2[Fe(CN)5NO] 261.97 Sodium nitroferrocyanide; sodium 

nitrosyl pentacyanoferrate (III) 

 Soluble in 2.3 parts of 

water, slightly soluble in 

alcohol 

a From Windholz (1983); ACGIH (2001); ECETOC (2004). 

 Cyanogen chloride is a colourless gas. Its common 

synonym is chlorine cyanide, and its common trade 

name is Caswell No. 267. Cyanogen chloride releases 

hydrogen cyanide by hydrolysis. Its conversion factors 

in air are: 

 1 ppm = 2.56 mg/m3 

1 mg/m3 = 0.391 ppm

 Common synonyms of acetone cyanohydrin are 

ACH, 2-cyano-2-propanol, 2-methyllactonitrile, and 2-

hydroxy-2-methyl propanenitrile. It dissociates on 

standing to liberate hydrogen cyanide. Its boiling point is 

120 °C (with decomposition to hydrogen cyanide and 

acetone). Its conversion factors in air are: 

 1 ppm = 3.54 mg/m3 

1 mg/m3 = 0.283 ppm

 The half-time of ACH in water was reported to be 

9 min (Ellington et al., 1986); further studies reported 

that this hydrolysis to acetone and hydrogen cyanide was 

pH dependent, and half-times of 58, 27, and 8 min were 

observed at pH 4.8, 6.3, and 6.8 (ICI, 1993). In a more 

recent study, similar findings were reported (half-times 

of 54.7, 31.2, 5.4, and 4.0 min at pH 6.00, 6.40, 6.86, 

and 7.00, respectively) (Frank et al., 2002). 

 Some chemical properties of other cyanides are 

given in Table 2. Copper cyanide is a white to creamcoloured solid. Its common name is cuprous cyanide, 

and its synonym is cupricin. Potassium silver cyanide 

occurs as white crystals; its common synonym is 

potassium dicyanoargentate. It is sensitive to light. 

Sodium ferrocyanide decomposes at 435 °C, forming 

sodium cyanide. 

 Cyanogenic glycosides are produced naturally by 

many plants; when hydrolysed, they produce hydrogen 

cyanide. Chemical structures of some commonly occurring cyanogenic glycosides are depicted in Figure 1. 

 Further chemical and physical properties of hydrogen cyanide and some cyanides are summarized in the 

International Chemical Safety Cards included in this 

document.
Concise International Chemical Assessment Document 61 

8 

Dhurrin (CAS No. 499-20-7) Linamarin (CAS No. 554-35-8) 

Amygdalin (CAS No. 29883-15-6) Lotaustralin (CAS No. 534-67-8) 

Prunasin (CAS No. 99-18-3) Taxiphyllin (CAS No. 21401-21-8) 

Fig. 1: Cyanogenic glycosides in major edible plants (JECFA, 1993) 

Amygdalin occurs in (among others) almonds, dhurrin in sorghum, linamarin in cassava, lotaustralin in cassava and lima beans, 

prunasin in stone fruits, and taxiphyllin in bamboo shoots.

3. ANALYTICAL METHODS

 Cyanides in environmental media are usually 

collected in sodium or potassium hydroxide solution and 

measured by spectrophotometry (Agrawal et al., 1991), 

colorimetry, or ion-specific electrode or by headspace 

gas chromatography with a nitrogen-specific detector or 

electron capture detector (Maseda et al., 1989; Seto et al, 

1993). Cyanide in aqueous matrices is usually measured 

by colorimetric, titrimetric (US EPA, 1983), or electrochemical methods after pretreatment to produce hydrogen cyanide and absorption in sodium hydroxide 

solution. Total cyanide (irrespective of origin) includes

all of the available cyanide in a sample; in drinkingwater, it is measured by semi-automated colorimetry 

(EPA Method 335.4) as well as by selective electrode, 

ultraviolet/distillation/spectrophotometry, and ion 

chromatography (EPA Method 300.0) (US EPA, 1993a). 

Free cyanide can also be determined by one method 

(SM-4500-CN-F) approved for drinking-water 

compliance monitoring analysis that does not require 

distillation, the specific ion electrode method (US EPA, 

2003a). Weak acid dissociable cyanide analysis (used 

principally by the precious metals mining industry) 

includes those cyanide species liberated at moderate pH 

4.5, such as aqueous hydrogen cyanide and cyanide 

anion, the majority of copper, cadmium, nickel, zinc, 

silver, and tin complexes, and others with similar low 

dissociation constants. Weak acid dissociable cyanide 

can be determined in wastewaters by a ligand 

exchange/flow injection/amperometric technique (EPA 

Method 1677) (Milosavlievic et al., 1995; US EPA, 

1997).

 A chromatographic technique with fluorescence 

detection is used to detect trace amounts of cyanide in 

blood cells (Chinaka et al., 1998). Cyanide in biological 

tissue and fluids can be measured spectrophotometrically 

after reaction with methaemoglobin. 

 Since many cyanides are unstable and emit volatile 

hydrogen cyanide gas, sampling, storage, and analysis 

must be done with caution, preferably immediately upon 

collection. 

 The three commonly used techniques (colorimetric, 

titrimetric, and electrochemical) may all suffer from 

interference problems, unless proper precautions are 

taken (ATSDR, 1989). 

HO

H

CH2OH

H O

OH

H

H

OH

H

O C

H

CN

OH

O

CH2OH

HO

OH

OH

H

H H

H

H

O C

CN

CH3

CH3

O

O

CH2OH

HO OH

OH

H

H H

H

H

CH2

O

HO OH

OH

H

H H

H

H

O

CN

CH

H

H

H

H

H

OH

OH

HO

CH2OH

O

O C

CN

CH3

O

O

CH2OH

HO

OH

OH

H

H H

H

H

CH

CN CN

CH

H

H

H H

H

OH

OH

HO

CH2OH

O

O OH
Hydrogen cyanide and cyanides: Human health aspects 

9 

 Metals suppress the transformation of cyanide to 

formic acid, thus lowering the measured hydrogen 

cyanide concentration (Dolzine et al., 1982). Carbonyl 

compounds also decrease the hydrogen cyanide recovery 

(Honig et al., 1983), as in the case with soybean 

samples, in which carbonyl compounds occur naturally. 

 Sodium thiosulfate can interfere with potentiometric 

(Sylvester et al., 1982) or colorimetric analysis 

(Ganjeloo et al., 1980). Care should be taken, since it is 

often used as an antidote to treat chemical poisoning. 

 Continuous monitoring of cyanide is also available 

using equipment based on diffusion and amperometric 

detection of hydrogen cyanide (NIOSH, 1976). 

 Detection limits for the different methods for 

hydrogen cyanide range from 0.8 to 400 mg/m3 for air 

samples, from 0.04 to 200 μg/litre for aqueous samples, 

and from 0.8 to 300 μg/litre for biological samples. 

NIOSH Method 7904 for workplace air has a limit of 

detection of 2.5 μg cyanide (NIOSH, 1994). 

 

4. SOURCES OF HUMAN AND 

ENVIRONMENTAL EXPOSURE 

4.1 Natural occurrence 

 Hydrogen cyanide is ubiquitous in nature. It is 

found in the stratosphere and non-urban troposphere (US 

EPA, 1990). It is released into the atmosphere from 

biomass burning, volcanoes, and natural biogenic 

processes from higher plants, bacteria, algae, and fungi 

(Fiksel et al., 1981; Cicerone & Zellner, 1983; Way, 

1984; ATSDR, 1997; Li et al., 2000). An estimate of the 

amount of cyanide released to the environment from 

natural biogenic processes is not available (ATSDR, 

1997). 

 Cyanide occurs naturally as cyanogenic glycosides 

in at least 2000 plants (Figure 1). Amygdalin (D-mandelonitrile-β-D-glucoside-6-β-D-glucoside) has been 

found in about 1000 species of plants, including cassava 

(tapioca, manioc), sweet potato, corn, cabbage, linseed, 

millet, and bamboo, in pits of stone fruits, such as 

cherries, peaches, and apricots, and in apple seeds 

(JECFA, 1993; Sharma, 1993; Padmaja, 1995). It is also 

present in bitter almonds and American white lima beans 

(Ermans et al., 1972). After ingestion, linamarin can be 

hydrolysed by either cassava linamarase or an endogenous β-glucosidase to yield D-glucose and ACH (Frakes 

et al., 1986a). 

4.2 Anthropogenic sources 

4.2.1 Production 

 Hydrogen cyanide is principally produced by two 

synthetic catalytic processes involving the reaction of 

ammonia and natural gas (or methane) with or without 

air. It is also obtained as a by-product in the production 

of acrylonitrile by the ammoxidation of propylene, 

which accounts for approximately 30% of the worldwide 

production of hydrogen cyanide. 

 Sodium and potassium cyanides are principally 

prepared by the direct reaction of hydrogen cyanide with 

the respective alkali in closed systems (European 

Chemicals Bureau, 2000a,b). Sodium cyanide is also 

prepared to a lesser extent by melting sodium chloride 

with calcium cyanamide or by heating sodium amide salt 

with carbon. 

 Calcium cyanide is produced by the reaction of 

coke, coal, and limestone. 

 Cyanogen chloride is a reaction product of organic 

precursors with hypochlorous acid in the presence of 

ammonia and may be formed as a by-product of the 

chloramination of water (WHO, 1996; IPCS, 2000a). 

 ACH was first produced in the 1930s as an intermediate in the production of methyl methacrylate from 

hydrogen cyanide. It is currently produced from the 

liquid-phase reaction of hydrogen cyanide and acetone 

in the presence of an alkali catalyst at atmospheric 

pressure (ECETOC, 2004). 

 Hydrogen cyanide capacity is generally treated as 

the sum of purposeful direct synthesis and that derived 

as a by-product of acrylonitrile production. Annual US 

hydrogen cyanide capacity by 11 companies in 1991 was 

666 000 tonnes. US production of hydrogen cyanide 

from 1983 to 1989 rose from 300 000 to 445 000 tonnes 

(Pesce, 1993). Output of hydrogen cyanide in the USA 

was 545 000 tonnes in 1992 (Cohrssen, 2001). Worldwide annual production and capacity of hydrogen 

cyanide in 1992 were estimated to be 950 000 and 

1 320 000 tonnes, respectively (Pesce, 1993; Cohrssen, 

2001). It has been estimated that the present total annual 

production of hydrogen cyanide worldwide is 1.4 million 

tonnes (Mudder & Botz, 2000). 

4.2.2 Use 

 In 1983, the major end uses of hydrogen cyanide in 

the USA were in the production of adiponitrile (200 000 

tonnes), ACH (128 000 tonnes), cyanuric chloride 

(28 500 tonnes), sodium cyanide (69 000 tonnes), 

chelating agents (15 800 tonnes), and nitrilotriacetic acid 

(10 100 tonnes) and for miscellaneous uses (20 000 
Concise International Chemical Assessment Document 61 

10 

tonnes) (US EPA, 1990). Hydrogen cyanide is also used 

in the production of methyl methacrylate, methionine 

and its hydroxylated analogues, and potassium cyanide 

(ATSDR, 1997; ECETOC, 2004). 

 Sodium cyanide is extensively employed in a large 

number of industrial processes, including electroplating 

and case-hardening of metals; the extraction (cyanidation) of gold and silver from ores; base metal flotation; 

coal gasification; and the fumigation of ships, railroad 

cars, buildings, grain silos, flour mills, seeds in vacuum 

chambers, and soil. Large quantities of sodium cyanide 

are used to introduce cyano groups into organic compounds, in particular through a reaction with organic 

halogen compounds to yield nitriles. The nitriles can 

then be converted to a variety of carboxylic acids, 

amides, esters, and amines. Potassium cyanide is used 

for electrolytic refining of platinum, for metal colouring, 

and as an electrolyte for the separation of gold, silver, 

and copper from platinum (Eisler et al., 1999; Patnaik, 

1999; ACGIH, 2001; ECETOC, 2004). Cyanide salts are 

used as chelating agents, and the complex cyanides of 

copper, zinc, and cadmium are used in electroplating 

processes, principally the plating of iron, steel, and zinc 

(ECETOC, 2004). 

 Calcium cyanide is used chiefly as a fumigant, 

because it readily releases hydrogen cyanide when 

exposed to air; as a fertilizer, defoliant, herbicide, and 

rodenticide; as a stabilizer for cement; and in stainless 

steel manufacture (ACGIH, 2001). 

 Cyanogen is used as a fumigant, as a fuel gas for 

welding and cutting heat-resistant metals, and as a rocket 

and missile propellant (ATSDR, 1997). 

 Cyanogen chloride is used as a fumigant gas and as 

a reagent in chemical synthesis. 

 Cuprous cyanide is used in plating baths for silver, 

brass, and copper–tin alloy plating (ATSDR, 1997), as 

an antifouling agent in marine paint, and as an insecticide and fungicide (Windholz, 1983). 

 Potassium silver cyanide is used in silver plating 

and as a bactericide. 

 Potassium ferricyanide is used chiefly for blueprints, in photography, for staining wood, in calico 

printing, and in electroplating. 

 Sodium ferrocyanide is used in ore flotation, as an 

anti-caking agent in rock salt, and in photography for 

bleaching, toning, and fixing. 

 Sodium nitroprusside has been used as an antihypertensive agent and in congestive heart failure and is 

used for deliberate induction of hypotension during 

certain neurosurgical procedures. 

 ACH is used in preparative transcyanohydrination 

reactions. 

4.2.3 Release to the environment 

 More than 30 large-scale accidental releases of 

cyanide to water systems have been reported since 1975; 

these include transportation accidents, pipe failures, and 

tailings dam-related releases (Korte et al., 2000; Mudder 

& Botz, 2000). 

 Non-point sources of cyanide released to water can 

result from runoff from cyanide-containing anti-caking 

salts (i.e., sodium ferrocyanide) used on roads, migration 

from landfills, and agricultural and atmospheric fallout 

and washout (ATSDR, 1997).

 The extraction of gold from low-grade ores by 

cyanidation processes was estimated to result in a 

worldwide emission of 20 000 tonnes of hydrogen 

cyanide into the atmosphere (Korte & Coulston, 1998). 

Another estimate suggested that currently 45 300 tonnes 

of cyanide are used in the USA in the cyanidation 

process. The wastes from these processes result in large 

cyanide-containing ponds near the mining operations 

(Clark & Hothem, 1991; Henny et al., 1994; Ma & 

Pritsos, 1997; Eisler et al., 1999). 

 The major point sources of cyanide release to water 

are discharges from gold mining plants, publicly owned 

wastewater treatment plants, iron and steel production, 

and the organic chemical industries. An estimated 

3 billion litres (i.e., 3 × 109

 litres) of wastes containing 

cyanides were generated in the USA in 1983, principally 

from spent cyanide plating bath solutions from electroplating operations (except for precious metals) and from 

spent stripping and cleaning bath solutions from electroplating operations (Grosse, 1986).

 During cassava starch production, large amounts of 

cyanoglycosides are released and hydrolysed by plantborne enzymes, leading to cyanide concentrations in 

wastewater as high as 200 mg/litre (Siller & Winter, 

1998). 

 The major sources of cyanide released to air, in 

addition to exhaust from vehicle emissions, are diverse, 

including chemical manufacturing (hydrogen cyanide, 

methyl methacrylate, acrylonitrile); processing 

industries, such as metallurgical industries and metal 

plating (i.e., electroplating metals and finishing [metal 

polishes]); extraction of gold and silver from low-grade 

ores; volatilization from cyanide wastes disposed of in 

landfills and waste ponds; the production of coke or 

other coal carbonization procedures; emissions from 
Hydrogen cyanide and cyanides: Human health aspects 

11 

municipal solid waste incinerators; and direct release of 

cyanides to the atmosphere resulting from fumigation 

operations, combustion of polyurethanes, acrylonitrile, 

and polyamide plastics, and combustion of wool, silk, 

and fibres (Carotti & Kaiser, 1972; Fiksel et al., 1981; 

ATSDR, 1997; Eisler et al., 1999). 

 An estimated total of 1 million tonnes of hydrogen 

cyanide, amounting to 73.1% of the total environmental 

releases in the USA, was discharged to the air from 

manufacturing and processing facilities (ATSDR, 1997). 

 The estimated amounts of hydrogen cyanide 

released to air in 1976 from the most common nonindustrial sources were as follows: agricultural pest 

control, 62 tonnes; incineration, 8.2–82 tonnes; and 

tobacco smoke, 5.9–340 tonnes (Fiksel et al., 1981; 

ATSDR, 1997). 

 In 2001, from various locations in the USA, about 

1300 tonnes of hydrogen cyanide were released on- and 

off-site; 540 tonnes were emitted to the atmosphere, 

0.1 tonne was released to surface waters, 770 tonnes 

were injected into Class I wells,1

 and 0.42 tonne was 

released to land (US EPA, 2003c). In 2001, from various 

locations in the USA, approximately 3400 tonnes of 

cyanides (not otherwise specified) were released on- and 

off-site; 220 tonnes were emitted to the atmosphere, 

47 tonnes were released to surface waters, 1800 tonnes 

were injected into Class I wells, and 1300 tonnes were 

released to land (US EPA, 2003c). 

 Hydrogen cyanide has been found following the 

combustion of a number of synthetic polymers. The 

maximum yield of hydrogen cyanide per gram of polyurethane foam ranged from 0.37 to 0.93 mg under nonflaming conditions and from 0.5 to 1.02 mg under 

flaming combustion (Sklarew & Hayes, 1984). Hydrogen cyanide concentrations in the off-gas from the shale 

oil retorting process ranged from 7 to 44 mg/m3

(Sklarew & Hayes, 1984). 

 One cigarette without a filter liberates 500 μg 

hydrogen cyanide, while filter cigarettes liberate only 

100 μg in mainstream smoke. Hydrogen cyanide 

concentrations in mainstream and sidestream smoke 

ranging from 280 to 550 μg/cigarette and from 53 to 

111 μg/cigarette, respectively, have been reported; 

sidestream:mainstream ratios of hydrogen cyanide 

concentrations ranged from 0.06 to 0.50 (ATSDR, 

1997). The level of hydrogen cyanide found in Canadian 

cigarette smoke under International Organization for 

Standardization standard smoking conditions were as 

 

1 Deep, isolated rock formations that are separated from the 

lowermost underground source of drinking-water by layers of 

impermeable clay and rock (US EPA, 2003b).

follows: mainstream smoke, 32–156 μg/cigarette; and 

sidestream smoke, 77–136 μg/cigarette (Health Canada, 

2002). 

 The average rate of emission of hydrogen cyanide 

by automobile exhaust was reported to be 7–9 mg/km 

for cars not equipped with catalytic converters and on 

the order of 0.6 mg/km for cars with catalytic converters 

operating under optimum conditions in the mid- to late 

1970s (ATSDR, 1997). 

 Cyanogen chloride is formed as a reaction product 

of organic precursors with hypochlorous acid in the 

presence of ammonia and may be formed as a byproduct of the chloramination of water (e.g., via the 

reaction of humic substances with chlorine and chloramine used for water disinfection) (Ohya & Kanno 

1987; WHO, 1996; IPCS, 2000a). In the USA, 35% of 

the surface water plants and 23% of the groundwater 

plants using chloramine as a primary or secondary 

disinfectant report cyanogen chloride formation (US 

EPA, 2002).

 Cyanogen is generated in the combustion of 

nitrogen–carbon compounds and appears in automobile 

exhaust gases and gases from blast furnaces 

(CHEMINFO, 1998). 

 Cyanide is present in the air mostly as a gas, and 

cyanides have the potential to be transported over long 

distances from their respective emission sources.

5. ENVIRONMENTAL LEVELS AND HUMAN 

EXPOSURE 

5.1 Environmental levels 

5.1.1 Air 

 Cyanide is found in ambient air as hydrogen cyanide and to a smaller extent in particulate matter. The 

concentration of hydrogen cyanide measured since 1981 

in the northern hemisphere’s non-urban troposphere 

ranged from 180 to 190 ng/m3

 (Cicerone & Zellner, 

1983; Jaramillo et al., 1989). 

 Ambient air monitoring data for cyanides in Bulgaria in areas near petrochemical plants showed concentrations ranging from 0.2 to 0.8 μg/m3

 (annual average 

value) (Kaloyanova et al., 1985). 

 Cyanide has been detected at levels of 20–46 mg/m3

in the air near large-scale cassava processing facilities in 

Nigeria (Okafor & Maduagwu, 2000). 
Concise International Chemical Assessment Document 61 

12 

5.1.2 Water 

 Cyanides, reported as cyanide, hydrogen cyanide, 

sodium cyanide, potassium cyanide, calcium cyanide, or 

copper(I) cyanide, have been detected in surface water 

samples at 70 of the 154 hazardous waste sites where 

they were studied in the USA; they have also been 

detected in groundwater samples at 191 of the 419 waste 

sites studied and in leachate samples of 16 of the 52 sites 

studied. The median concentrations in the positive 

samples were 160 μg/litre for groundwater, 70 μg/litre 

for surface water, and 479 μg/litre for the leachates 

(HazDat, 2003). 

 Data from the US National Urban Runoff Program 

in 1982 revealed that 16% of urban runoff samples 

collected from four cities across the USA contained 

cyanides at levels of 2–33 μg/litre (ATSDR, 1997). 

 According to the US Environmental Protection 

Agency’s (EPA) STORET database, the mean cyanide 

concentration in most surface waters in the USA is less 

than 3.5 μg/litre. Data from the late 1970s to early 1980s 

indicated that the levels are higher only in limited areas 

and may exceed 200 μg/litre (ATSDR, 1997). 

 In 1978, a US EPA survey of drinking-water 

supplies showed that about 7% of the supplies had 

cyanide concentrations greater than 10 μg/litre (US 

EPA, 1993a). Cyanogen chloride is one of the 18 compounds that occur most frequently (8 of 10 city surveys) 

in potable water within the framework of the US 

National Organic Reconnaissance Survey (Bedding et 

al., 1982). In a survey in 1987 of over 35 drinking-water 

supplies, the quarterly median cyanogen chloride 

concentrations in drinking-water ranged from 0.45 to 

0.80 μg/litre (from 0.19 to 0.34 μg cyanide/litre) 

(Krasner et al., 1989; ATSDR, 1997). More current data 

regarding the cyanide and cyanogen chloride levels in 

drinking-water are lacking. 

 Levels of 1.58–7.89 mg cyanide/litre have been 

found in natural water sources near large-scale cassava 

processing facilities in Nigeria (Okafor et al., 2001). 

5.1.3 Soil 

 Cyanide has been identified in the soil of hazardous 

waste sites in the USA; the median concentrations for 

the positive sites were 0.8 mg/kg in the subsurface soil 

(found at 77 sites of the 124 studied) and 0.4 mg/kg in 

the topsoil (51 positive sites out of 91 sites) (HazDat, 

2003). 

 Cyanide-containing wastes are commonly found in 

soils at former manufactured gas plant sites in the USA. 

Most concentrations of cyanide compounds at the 

manufactured gas plant sites are below 2000 mg/kg. The 

most prevalent types of cyanide compounds are ironcomplexed forms, e.g., ferric ferrocyanide (Prussian 

blue), rather than the highly toxic free cyanide forms. 

Iron-complexed cyanides, dominated by the ferrocyanide 

ion, comprise over 97% of total cyanides in either 

weathered or unweathered soils (Shifrin et al., 1996). 

5.1.4 Food 

 Many edible plants contain cyanogenic glycosides, 

whose concentrations can vary widely as a result of 

genetic and environmental factors, location, season, and 

soil types (Ermans et al., 1980; JECFA, 1993). Some of 

the foodstuffs and their cyanide contents are shown in 

Table 3. Cassava tubers vary widely in their cyanogenic 

glycoside content, although most varieties contain 15–

400 mg cyanide/kg fresh weight. Occasionally varieties 

of cassava tubers contain 1300–2000 mg cyanide/kg 

fresh weight, and cassava leaves contain 1000–2000 mg 

cyanogenic glucosides/kg on a dry matter basis 

(Padmaja, 1995). Fermentation of cassava pulp for 96 h 

during gari production reduced the hydrogen cyanide

content by 50%; soaking of sliced cassava for 24 h, 

40%; and sun-drying, some 15% (Kendirim et al., 1995). 

It should be noted that the ranges of cyanide concentrations shown in Table 3 are very broad in several cases 

(i.e., cereals and their products, soy protein products, 

and apricot pits), which may be due to their different 

sources and differences in analytical procedures; as well, 

the values may reflect the older literature. 

 Hydrogen cyanide can be produced by hydrolytic 

reaction catalysed by one or more enzymes from the 

plants containing cyanogenic glycosides. In kernels, for 

example, this reaction is catalysed by the enzyme 

emulsin (Lasch & El Shawa, 1981) when the seeds are 

crushed and moistened. Amygdalin (which is also 

present in cassava, bitter almonds, and peach stones) is 

converted to glucose, benzaldehyde, and hydrogen 

cyanide (Figure 2) (IPCS, 1992). Hydrogen cyanide 

release can occur during maceration, which activates 

intracellular β-glucosidases. This reaction can also result 

from chewing, which causes the enzyme and the 

cyanogenic glycosides stored in different compartments 

to combine (Ermans et al., 1980; Nahrstedt, 1993). The 

reaction occurs rapidly in an alkaline environment, and 

the hydrolysis is complete in 10 min. Hydrolysis is 

possible in an acid solution and takes place slowly. 

 Liberation of hydrogen cyanide from cyanogenic 

glycosides occurs usually after ingestion and hydrolysis 

by the glycosidases of the intestinal microflora and, to a 

lesser degree, by glucosidases of the liver and other 

tissues (Padmaja, 1995). However, hydrolysis may also 

occur during the preparation of the food, which may 

account for the short interval between ingestion and the 

appearance of signs of poisoning in some accidents 

(Lasch & El Shawa, 1981). 
Hydrogen cyanide and cyanides: Human health aspects 

13 

Table 3: Cyanide concentrations in food products.a 

Type of product 

Cyanide

concentration (in 

mg/kg or mg/litre) 

Cereal grains and their products 0.001–0.45 

Soy protein products 0.07–0.3 

Soybean hulls 1.24 

Apricot pits, wet weight 89–2170 

Home-made cherry juice from pitted 

fruits 

5.1 

Home-made cherry juice containing 

100% crushed pits 

23 

Commercial fruit juices 

Cherry 4.6 

Apricot 2.2 

Prune 1.9 

Tropical foodstuffs 

Cassava (bitter) / dried root cortex 2360 

Cassava (bitter) / leaves 300 

Cassava (bitter) / whole tubers 380 

Cassava (sweet) / leaves 451 

Cassava (sweet) / whole tubers 445 

Gari flour (Nigeria) 10.6–22.1 

Sorghum / whole immature plant 2400 

Bamboo / immature shoot tip 7700 

Lima beans from Java (coloured) 3000 

Lima beans fom Puerto Rico (black) 2900 

Lima beans from Burma (white) 2000 

a

 From Nartey (1980); Honig et al. (1983); JECFA (1993); 

ATSDR (1997). 

5.1.5 Other

 Laetrile (another name for amygdalin derived from 

apricot kernels), which was formerly used as an anticancer agent, releases cyanide upon metabolism. Bitter 

almonds and apricot pits containing cyanogenic glycosides are still sold in health food stores and over the 

Internet (Suchard et al., 1998). Other drugs, such as 

sodium nitroprusside, which is used as an antihypertensive and in congestive heart failure (Guiha et al., 

1974; Tinker, 1976; Aitken et al., 1977; Schultz, 1984; 

Rindone & Sloane 1992), also liberate hydrogen cyanide 

in the body. In sodium nitroprusside, the CN–

 moiety 

represents 44% by weight of the molecule. Some 

aliphatic nitriles that are widely used in the chemical 

industry — i.e., acetonitrile (IPCS, 1993), acrylonitrile 

(IARC, 1999), succinonitrile, and adiponitrile — also 

release cyanide upon metabolism (Willhite & Smith, 

1981).

5.2 Human exposure 

5.2.1 General population 

 The general population may be exposed to cyanide 

from ambient air, drinking-water, and food. 

 Based on an atmospheric hydrogen cyanide 

concentration of 190 ng/m3

 and an average daily 

inhalation of 20 m3

 air, the inhalation exposure of the 

general US non-urban, non-smoking population to 

hydrogen cyanide is estimated to be 3.8 μg/day 

(ATSDR, 1997). 

 Based on a daily drinking-water consumption of 

2 litres for an adult, the daily intake of cyanogen 

chloride is estimated to be 0.9–1.6 μg (equivalent to 0.4–

0.7 μg of cyanide) (ATSDR, 1997) for cyanogen 

chloride concentrations in water of 0.45–0.80 μg/litre 

(0.19–0.34 μg cyanide/litre). 

 Among the general population, subgroups with the 

highest potential for exposure to cyanide include active 

and passive smokers, individuals involved in large-scale 

processing of foods high in cyanogenic glycosides, 

individuals consuming foods high in cyanogenic glycosides, and, to a lesser degree, fire-related smoke inhalation victims. 

 Human exposure to cyanide by dietary intake is 

estimated to be potentially of major significance for 

cassava-consuming populations; cassava has been 

estimated to be the staple food for 500 million people. 

However, data on the concentrations of cyanides in the 

total diet are lacking; hence, the daily cyanide intake 

from food cannot be calculated. For human consumption, cassava can be eaten raw, cooked, or grated and 

roasted into flour and eaten as “gari,” which is the 

common form in Nigeria (Kendirim et al., 1995). In 

Mozambique, it was estimated that in families affected 

by the “mantakassa” disease (spastic paraparesis; see 

section 8), the daily intake of cyanogens was 14–30 mg 

(as cyanide) at the time of a mantakassa epidemic in 

1981 (Ministry of Health, Mozambique, 1984b). In 

Nigeria, it was estimated that the intake of hydrogen 

cyanide in the tropical ataxia-endemic areas may be as 

high as 50 mg/day (Osuntokun, 1981).

 Urinary excretion of thiocyanate has been applied in 

the biological monitoring of exposure to cyanogenic 

glycosides, especially among cassava-consuming populations. The average urinary thiocyanate concentration 

among children in the Bandundu region of the Democratic Republic of the Congo (formerly Zaire) was 

757 μmol/litre in the south and 50 μmol/litre in the north 

(both populations consumed cassava as their staple diet, 

but the cassava was well processed in the north and
Concise International Chemical Assessment Document 61 

14 

2 H2O + 

 

2 + HCN + 

Water + amygdalin → 2 glucose + cyanide + benzaldehyde 

Fig. 2: Hydrolysis of amygdalin 

inadequately processed in the south). These concentrations can be compared with an average of 31 μmol/litre 

in a non-smoking Swedish reference population (BaneaMayambu et al., 2000). In the same Bandundu region, it 

was shown that there was a marked seasonal variation in 

urinary thiocyanate concentrations in the villages with a 

high “konzo” (spastic paraparesis) incidence (563–

627 μmol/litre in the dry season and 344–381 in the wet 

season), while the average in non-konzo areas was 

241 μmol/litre (Banea-Mayambu et al., 1997). In 

Mozambique, the average urinary thiocyanate levels 

among healthy children from areas with epidemic spastic 

paraparesis varied between 33 and 1175 μmol/litre, 

whereas levels in areas with no paraparesis were 

between 18 and 400 μmol/litre (Casadei et al., 1990). In 

Nampula province in Mozambique, where spastic paraparesis epidemics had been observed in 1981–1982 and 

during the civil war in 1992–1993, average urinary thiocyanate concentrations among schoolchildren in five 

areas were between 225 and 384 μmol/litre in October 

1999 (Ernesto et al., 2002). In Malawi, in an area where 

cassava was typically soaked for 3–6 days for processing 

to flour, urinary thiocyanate concentrations were 

between 2 and 410 μmol/litre, with a median of 

32 μmol/litre (Chiwona-Karltun et al., 2000). 

5.2.2 Occupational exposure 

 The principal routes of occupational exposure to 

cyanides are via inhalation and, to a lesser degree, skin 

absorption. Skin absorption may be significant under 

some circumstances — for example, when airborne 

concentrations are very high, such as in fumigation 

operations. It may occur as well when personal 

protection is inadequate and operators are splashed. 

 Workers involved in electroplating, metallurgy, 

pesticide application, firefighting, gas works operations, 

tanning, blacksmithing, metal cleaning, photoengraving, 

photography, and the manufacture of steel, cyanides, 

adiponitrile and other nitriles, methyl methacrylate, 

cyanuric acid, dyes, pharmaceuticals, or chelating agents 

have the potential to be occupationally exposed to higher 

concentrations of cyanide (Prohorenkov & Kolpakov, 

1978; Philips, 1989; IPCS, 1992; Banerjee et al., 1997). 

 A number of illustrative levels of cyanide in the 

breathing zone of workers in working environments 

monitored at different production facilities in the USA 

during the period 1976–1982 have been reported. The 

concentration of cyanide in air at a plating facility of a 

national airline was 0.001–0.004 mg/m3

 (NIOSH, 1982). 

Concentrations of hydrogen cyanide in air at a plating 

facility of an electrical and electronic company in 

Virginia, USA, ranged from 0.07 mg/m3

 in a salt pot 

room to 4.3 mg/m3

 in a stripping tank (NIOSH, 1976). 

The concentration of cyanide in air at a plating facility in 

Ohio, USA, was 1.7 mg/m3

 (NIOSH, 1978). 

6. COMPARATIVE KINETICS AND 

METABOLISM IN LABORATORY ANIMALS 

AND HUMANS

6.1 Absorption 

 Hydrogen cyanide is readily absorbed following 

inhalation, oral, and dermal exposure. Following 

exposure to cyanide in the atmosphere, toxic amounts of 

cyanide are absorbed with great rapidity through the 

bronchial mucosa and alveoli (ATSDR, 1997). Humans 

retained 58% of the hydrogen cyanide in the lungs after 

inhaling the gas through normal breathing (Landahl & 

Herrmann, 1950; ATSDR, 1997). Alkali metal cyanides 

are rapidly absorbed from the gastrointestinal tract. 

Absorption is affected by the presence of food in the gut, 

the pH of the gut, and the lipid solubility of the cyanide 

compound. 

 Gastrointestinal absorption of inorganic cyanide 

salts is slower than pulmonary absorption, and the onset 

of symptoms is delayed and the severity of symptoms 

diminished compared with inhalation. When simple 

cyanide salts such as potassium and sodium cyanide are 

ingested, free cyanide ion can rapidly bind hydrogen ion 

to form hydrogen cyanide in the highly acidic medium 

of the stomach. Essentially all cyanide ingested as 

cyanide salts will form hydrogen cyanide and will be 

quickly absorbed. However, after oral intake, only part 

O

O

CH2OH

HO OH

OH

H

H H

H

H

CH2

O

HO OH

OH

H

H H

H

H

O

CN

CH CHO

H

H

H H

H

OH

OH HO

CH2OH

O OH
Hydrogen cyanide and cyanides: Human health aspects 

15 

of the dose reaches the blood due to first-pass metabolism by the liver (ECETOC, 2004). 

 Liquid cyanide compounds are easily absorbed 

through intact skin upon direct contact due to their lipid 

solubility and rapid epidermal penetration. Skin 

absorption of vapours of hydrogen cyanide is also 

possible when the air concentrations are high. The 

amount and rate of absorption of cyanides from aqueous 

solutions or atmospheric hydrogen cyanide depend upon 

the presence of moisture in the skin, concentration and 

pH of the solution, the surface area of contact, and the 

duration of contact (Dugard, 1987). In vitro studies with 

human skin have shown that penetration of sodium 

cyanide in aqueous solution through skin decreases with 

increasing pH (increasing dissociation), reflecting the 

more rapid absorption of the undissociated hydrogen 

cyanide. The permeability constant measured for the 

cyanide ion in aqueous solution was 3.5 × 10–4 cm/h, and 

that calculated for hydrogen cyanide was 1 × 10–4 cm/h 

(Dugard, 1987). 

6.2 Distribution 

 Hydrogen cyanide has a pKa of 9.22; thus, at 

physiological pH (about pH 7), hydrocyanic acid is 

distributed in the body as hydrogen cyanide and is not 

present as the free cyanide ion. Hence, the form of 

cyanide to which exposure occurs, the salt or the free 

acid, does not influence distribution, metabolism, or 

excretion from the body (ECETOC, 2004). Inhaled or 

percutaneously absorbed hydrogen cyanide passes 

immediately into the systemic circulation. The distribution of cyanide to the various tissues is rapid and fairly 

uniform. Somewhat higher levels are generally found in 

the liver, lungs, blood, and brain. The tissue levels of 

hydrogen cyanide were 0.75, 0.42, 0.41, 0.33, and 

0.32 mg/100 g of tissue in lung, heart, blood, kidney, 

and brain, respectively, in a man who died following 

inhalation exposure to hydrogen cyanide gas (Gettler & 

Baine, 1938; Ballantyne, 1983a; ATSDR, 1997; 

ECETOC, 2004). In contrast, high proportions of 

ingested sodium and potassium cyanide will pass 

through the liver and are detoxified by the first-pass 

effect. 

 The major portion of cyanide in blood is sequestered in the erythrocytes, and a relatively small proportion is transported via the plasma to target organs. 

Cyanide is concentrated in red blood cells at a red blood 

cell to plasma ratio of 199:1; levels in plasma reflect 

tissue levels better than levels in whole blood or erythrocytes. Small but significant levels of cyanide are found 

in normal blood plasma (<140 μg/litre) and other tissues 

(<0.5 mg cyanide/kg) of humans without known occupational cyanide exposure (Feldstein & Klendshoj, 1954). 

These levels are related mostly to exposure to cyanogenic food, vitamin B12, and tobacco smoke. A detailed 

survey of normal plasma cyanide levels in 10 cases 

showed a maximum level of 106 μg/litre, with a mean of 

48 μg/litre (Feldstein & Klendshoj, 1954). After cessation of exposure, plasma cyanide levels tend to return to 

normal within 4–8 h (Feldstein & Klendshoj, 1954; 

Ansell & Lewis, 1970). 

 In rats dosed by gavage, highest concentrations of 

cyanide were found in the liver, followed by the lungs 

and blood (Yamamoto et al., 1982). After inhalation 

exposure, the highest concentrations of cyanide in rats 

were found in the lungs, followed by the blood and liver. 

 Cyanide has not been shown to accumulate in the 

blood and tissues following oral exposue to inorganic 

cyanide (ATSDR, 1997), and no cumulative effect on 

the organism during repeated exposure has been demonstrated. There is a cumulative effect of exposure to thiocyanate (from the breakdown of cyanogenic glycosides 

in food plants), resulting in thyroid toxicity, including 

goitre and cretinism (Nahrstedt, 1993). 

 A number of illustrative levels of cyanide in organs 

and blood after oral intake in humans (Ansell & Lewis, 

1970; ATSDR, 1997) and rabbits (Ballantyne, 1983a) 

have been reported. For a given exposure route, whole 

blood and serum cyanide levels are quite similar for 

different species (Ballantyne, 1983a). 

6.3 Metabolism and excretion 

 Although cyanide can interact with substances such 

as methaemoglobin in the bloodstream, the majority of 

cyanide metabolism occurs within the tissues. Cyanide is 

metabolized in mammalian systems by one major route 

and several minor routes. The major route of metabolism 

for hydrogen cyanide and cyanides is detoxification in 

the liver by the mitochondrial enzyme rhodanese, which 

catalyses the transfer of the sulfane sulfur of thiosulfate 

to the cyanide ion to form thiocyanate (Figure 3) 

(Williams, 1959; Ansell & Lewis, 1970). About 80% of 

cyanide is detoxified by this route. The rate-limiting step 

is the amount of thiosulfate. While rhodanese is present 

in the mitochondria of all tissues, the species and tissue 

distributions of rhodanese are highly variable. In 

general, the highest concentrations of rhodanese are 

found in the liver, kidney, brain, and muscle, but the 

supply of thiosulfate is limited (Aminlari et al., 1994). 

Rhodanese is present in rat nasal mucosal tissues, 

particularly in the olfactory region, at a 7-fold higher 

concentration (on a per milligram of mitochondrial 

protein basis) than in the liver (Dahl, 1989). Dogs have a 

lower overall activity of rhodanese than monkeys, rats, 

and rabbits (ATSDR, 1997).
Concise International Chemical Assessment Document 61 

16 

Fig. 3: Basic processes involved in the metabolism of cyanide (ATSDR, 1997) 

 A number of other sulfur transferases can also 

metabolize cyanide, and albumin, which carries 

elemental sulfur in the body in the sulfane form, can 

assist in the catalysis of cyanide to thiocyanate as well 

(Sylvester et al., 1982; Westley et al., 1983). Cyanide 

and thiocyanate can also be metabolized by several 

minor routes, including the combination of cyanide with 

hydroxycobalamin (vitamin B12a) to yield cyanocobalamin (vitamin B12) (Boxer & Rickards, 1952) and the 

non-enzymatic combination of cyanide with cystine, 

forming 2-iminothiazoline-4-carboxylic acid, which 

appears to be excreted without further change (Rieders, 

1971) (Figure 3). 

 In studies with rats orally administered potassium 

cyanide and maintained for up to 4 weeks on either a 

balanced diet or a diet lacking the sulfur amino acids Lcystine and L-methionine, a strongly positive linear 

relationship was found between blood cyanide and 

plasma cyanate (OCN–

) concentration (Tor-Agbidye et 

al., 1999). It was suggested that in Africa, where there 

are protein-deficient populations whose levels of sulfurcontaining amino acids are low, cyanide (from prolonged use of cassava) may conceivably be converted to 

cyanate, which is known to cause neurodegenerative 

disease in humans and animals. 

 While absorbed cyanide is principally excreted as 

thiocyanate in the urine, traces of free hydrogen cyanide 

may also be excreted unchanged in the lungs, saliva, 

sweat, or urine (Hartung, 1982), as carbon dioxide in 

expired air, or as β-thiocyanoalanine in saliva and sweat 

S

NH

NH2

COOH

S

NH

NH

COOH

CN

S CH2CH COOH

NH2

S

S CH2CH COOH

NH2

CH2CH

NH2

COOH

HCNO

CO2

HCOOH

ß-Thiocyanoalanine

2-Aminothiazoline4-carboxylic acid

2-Iminothiazolidine4-carboxylic acid

Minor 

pathway

Major pathway

(80%)

Cystine

1 / 2

Metabolism of 

one-carbon

compounds

Formates

Some excreted

in urine

Cyanocobalamin

(Vitamin B12)

CN -

Cyanide

HCN

(expired air)

SCN -

Thiocyanate
Hydrogen cyanide and cyanides: Human health aspects 

17 

(Friedberg & Schwartzkopf, 1969; Hartung, 1982; 

JECFA, 1993). 

 Thiocyanate was found in the urine of non-exposed 

people at average concentrations of 2.16 mg/litre urine 

for non-smokers and 3.2 mg/litre urine for smokers 

(Chandra et al., 1980). Urinary excretion of thiocyanate 

was monitored in a man after ingestion of about 3–5 g 

potassium cyanide (15–25 mg cyanide/kg body weight) 

(Liebowitz & Schwartz, 1948; ATSDR, 1997). The 

results indicated that the patient excreted 237 mg of 

thiocyanate over a 72-h period. This quantity was substantially more than the normal average amount of thiocyanate in urine, which varies from 0.85 to 14 mg/24 h 

(ATSDR, 1997). 

 The limiting factor in cyanide metabolism is the low 

concentration of the sulfur-containing substrates in the 

body — primarily thiosulfate, but also cystine and 

cysteine. The rate of spontaneous detoxification of 

cyanide in humans is about 1 μg/kg body weight per 

minute (Schultz et al., 1982), which is considerably 

slower than in small rodents (Schubert & Brill, 1968) or 

dogs (Lawrence, 1947). 

 After administration of an intravenous dose of 3–

4 mg potassium cyanide to beagle dogs, blood levels 

decreased in a manner consistent with first-order 

elimination kinetics for the first 80 min (Bright & Marrs, 

1988). The half-time for this phase was about 24 min, 

corresponding to an elimination rate constant of 

0.03/min. After 80 min, the blood cyanide concentrations fell at a slower rate, with a half-time of 5.5 h. In 

rats, after a single oral dose, the blood elimination halftime of cyanide was 14.1 min, corresponding to a rate 

constant of 0.05/min (Leuschner et al., 1991). 

 Rats treated orally with 2 mg cyanide/kg body 

weight excreted 47% of the dose in the urine within 24 h 

(Farooqui & Ahmed, 1982). A [14C]cyanide intake study 

with rats (exposed to a regular intake of cyanide in the 

diet for 3 weeks) indicated the existence of a gastrointestinal circulation of thiocyanate, in which a substantial amount of thiocyanate, which was excreted into the 

stomach contents of the rat, was reabsorbed by the 

intestine into the body fluid, to be partly excreted in the 

urine and partly resecreted into the gastric contents 

(Okoh & Pitt, 1982). The relative proportion of cyanide 

to thiocyanate in body fluids is about 1:1000 (Pettigrew 

& Fell, 1973). The half-time for hydrogen cyanide 

elimination is about 1 h (Ansell & Lewis, 1970; IPCS, 

1992). 

 Half-time values of the principal metabolite thiocyanate in humans have been reported as 4 h (Blaschle 

& Melmon, 1980), 2 days (Bödigheimer et al., 1979), 

and 2.7 days (Schultz et al., 1979). In patients with renal 

insufficiency, a mean half-time of 9 days was reported 

(Bödigheimer et al., 1979). 

6.4 Biological monitoring 

 Levels of the cyanide metabolite thiocyanate in 

blood serum and plasma and urine have been employed 

as indicators of high cyanide exposure in humans 

(Lauwerys & Hoet, 2001). However, at low levels of 

occupational exposure, the relationship between exposure and urinary thiocyanate concentrations shows a 

wide inter- and intraindividual variation due to a variety 

of factors (e.g., diet); therefore, measuring cyanide 

and/or thiocyanate levels in blood and urine is not a 

reliable biomarker for exposure to low concentrations of 

cyanide. 

7. EFFECTS ON LABORATORY MAMMALS 

AND IN VITRO TEST SYSTEMS 

7.1 Single exposure 

 Symptoms of cyanide toxicity can occur within 

seconds of inhalation of hydrogen cyanide or within 

minutes of ingestion of cyanide salts. Onset may be 

delayed up to 12 h after ingestion of cyanogenic glycosides, nitriles, or thiocyanates. 

 Inhalation LC50 values of hydrogen cyanide in rats 

ranged from 158 mg/m3

 for 60 min to 3778 mg/m3 for 

10 s (Ballantyne, 1983a). Exposure of mice to cyanide 

resulted in similar LC50 values (Higgins et al., 1972; 

Matijak-Schaper & Alarie, 1982), and LC50 values of 

hydrogen cyanide in rabbits ranged from 2432 mg/m3

 for 

45 s to 208 mg/m3

 for 35 min (Ballantyne, 1983a). The 

concentration of hydrogen cyanide in inhaled air 

markedly affects the acute toxicity: the total amount of 

hydrogen cyanide inhaled leading to death is disproportionately larger at low exposure levels than at high 

exposure levels (and thus the time leading to death is 

disproportionately longer) (Table 4). A similar dose rate 

dependence of acute toxicity was observed in hamsters: 

(pregnant) hamsters did not show signs of toxicity until 

they had received a total dose of 30–40 times the single 

subcutaneous LD50 when given sodium cyanide subcutaneously by an osmotic minipump (Doherty et al., 

1982). 

 A similar dose rate dependence has also been noted 

for oral exposure. While the single-dose gavage LD50

of potassium cyanide was 10 mg/kg body weight in 

Sherman rats, no mortality was observed when a dose 

of 250 mg/kg body weight was given in the diet for 

90 days. The author ascribed this remarkable difference 
Concise International Chemical Assessment Document 61 

18 

to the difference in dose rate (bolus vs. dietary exposure): at the low dose rate, the liver is capable of 

detoxifying cyanide before it reaches the general 

circulation (Hayes, 1967). 

Table 4: Acute inhalation toxicity of hydrogen cyanide 

vapour in rats.a

 

Median lethal toxicity 

Exposure time 

as LC50 

(mg/m3

) 

as total doseb

 

(min × mg/m3

) 

10 s 3778 631 

1 min 1471 1129 

5 min 493 2463 

30 min 173 5070 

60 min 158 9441 

a

 From Ballantyne (1983a). 

b

 Details of calculation not provided. 

 The information on the relative sensitivity of 

various animals to hydrogen cyanide vapours is mainly 

based on early studies by Barcroft (1931). In an extensive series of inhalation experiments, in which different 

species of animals were exposed to usually 5–8 different 

concentrations of hydrogen cyanide and followed until 

death, he showed that the lethal time (time for 50% of 

animals to die at 1000 mg/m3

) was 0.8, 1.0, 1.0, 1.0, 2.0, 

2.0, 3.0, and 3.5 min for dogs, mice, cats, rabbits, rats, 

guinea-pigs, goats, and monkeys. Extrapolation to zero 

mortality gave the following maximal non-lethal concentrations to dogs, rats, mice, rabbits, monkeys, cats, goats, 

and guinea-pigs: 100, 100, 140, 180, 180, 180, 240, and 

400 mg/m3

. There was thus a rough inverse relationship 

between sensitivity to hydrogen cyanide and body size, 

dogs being a notable exception. 

 Severe dyspnoea has been observed in dogs exposed 

to 170–740 mg hydrogen cyanide/m3

 for 2–12 min. 

Pulmonary oedema was found in some dogs at necropsy 

(Haymaker et al., 1952). Exposure of cynomolgus 

monkeys to 110–180 mg hydrogen cyanide/m3

 led 

quickly to incapacitation; the time to incapacitation was 

inversely related to the level of exposure, being 8 min 

for 180 mg/m3

 and 19 min for 110 mg/m3 (Purser et al., 

1984). At 70 mg/m3

 for 30 min, slight depression of the 

central nervous system was reported (Purser, 1984). 

 Following oral administration to rats, LD50s of 

hydrogen cyanide, sodium cyanide, and potassium cyanide are very similar: 0.156, 0.117, and 0.115 mmol/kg 

body weight, respectively, i.e., 3–4 mg cyanide/kg body 

weight (Ballantyne, 1983a1

). In mice, an LD50 of 

15.8 mg potassium cyanide (corresponding to 6 mg 

cyanide)/kg body weight has been reported (Ferguson, 

 

1 In Table 1 of Ballantyne (1983a), the rat oral LD50 values are 

erroneously listed as coming from rabbits (Ballantyne, 1987).

1962). In rabbits, hydrogen cyanide, potassium cyanide, 

and sodium cyanide appear equitoxic on a molar basis 

(LD50s of 0.092, 0.104, and 0.090 mmol/kg for hydrogen 

cyanide, sodium cyanide, and potassium cyanide, 

respectively); rabbits appeared to be somewhat more 

susceptible to cyanides than mice or rats (Ballantyne, 

1983a). 

 Following application of cyanides in aqueous solution to the intact skin of New Zealand rabbits, the dermal 

LD50s of hydrogen cyanide, sodium cyanide, and potassium cyanide were 0.260, 0.298, and 0.343 mmol/kg 

body weight, respectively (corresponding to 6.8, 7.7, and 

8.9 mg cyanide/kg body weight) (Ballantyne, 1983a). 

The dermal toxicity of cyanide, especially of hydrogen 

cyanide, is markedly greater following application on 

abraded skin, which enhances the penetration of cyanide 

(LD50s of 0.087, 0.220, and 0.30 mmol/kg for hydrogen 

cyanide, sodium cyanide, and potassium cyanide, 

respectively) (Ballantyne, 1987).2

 Local contact may 

produce mild burns (IPCS, 1992). 

 In a range-finding toxicity study on ACH, the oral 

LD50 in rats and dermal LD50 in rabbits were both 17 mg 

ACH (5.2 mg cyanide)/kg body weight; 4-h inhalation 

mortality in rats was 2/6 at 220 mg/m3

 and 6/6 at 

440 mg/m3

 (Smyth et al., 1962). In a 4-week inhalation 

study, in which the average measured concentrations of 

ACH were 33, 106, and 211 mg/m3

, 3/10 male rats died 

after the first 6-h exposure at the highest concentration 

(Monsanto Co., 1985c). On this first day of exposure, 

the four measured concentrations of ACH in the chamber were 196, 214, 225, and 225 mg/m3

, 225 mg/m3

being the highest individual concentration measured 

during the 1-month exposure (when no further mortality 

was observed). No similar acute mortality was observed 

in a 14-week study at exposures up to 204 mg/m3

, in the 

male fertility study (202 mg/m3

), or in the female fertility study (207 mg/m3

) (see sections 7.3 and 7.6) (Monsanto Co., 1984a, 1985a,b). 

 There are no qualitative differences in acute poisoning between cyanide compounds, since the cyanide ion 

is the common agent that primarily inhibits tissue cytochrome oxidase activity in rats, mice, and rabbits, with 

resulting anoxia (Way, 1984; US EPA, 1988). Although 

acute oral doses of cyanide cause cardiovascular, respiratory, and neuroelectric alterations, many studies have 

shown that the brain is the organ most sensitive to cyanide toxicity. Death from cyanide poisoning is believed 

to result from central nervous system depression, subsequent to inhibition of brain cytochrome oxidase 

activity (Way, 1984). Typical signs of toxicity after 

inhalation of hydrogen cyanide in test species include 

rapid breathing, weak and ataxic movements, 

 

2 The information on the exposure regimen in these studies is 

incomplete.
Hydrogen cyanide and cyanides: Human health aspects 

19 

convulsions, loss of voluntary movement, coma, and 

decrease and irregularities in respiratory rate and depth 

preceding death (Ballantyne, 1983b; European Chemicals Bureau, 2000a,b).

7.2 Short-term exposure 

7.2.1 Oral 

 Forty-six male adult inbred Wistar rats were used in 

four experimental groups and one control group and 

treated with 0, 0.3, 0.9, 3.0, or 9.0 mg potassium cyanide/kg body weight per day in the drinking-water for 

15 days. This was equivalent to 0, 0.12, 0.36, 1.2, and 

3.6 mg cyanide/kg body weight per day. The high-dose 

group exhibited a 70% lower body weight gain than the 

control animals. In qualitative histological analysis, 

without statistical treatment or morphometric analysis, 

changes were observed in the kidney, liver, and thyroid. 

Cytoplasmic vacuolation, considered to reflect hydropic 

degeneration of proximal tubular epithelial cells, was 

noted in animals treated at doses of 3.0–9.0 mg 

potassium cyanide/kg body weight per day and in 

hepatocytes of those animals treated at a dose of 9.0 mg 

potassium cyanide/kg body weight per day. A dosedependent increase in the number of reabsorption 

vacuoles on follicular colloid in the thyroid gland was 

noted in all animals of the experimental groups. No 

changes were observed in serum triiiodothyronine (T3), 

thyroxine (T4), creatinine, or urea levels; a decrease was 

observed in serum alanine aminotransferase (ALAT)

activity at the two lowest exposure levels. Serum aspartate aminotransferase (ASAT) was elevated by 30% at 

the two lowest dose levels and by 21% at the 3.0 mg 

potassium cyanide/kg body weight per day dose; it was 

decreased by 29% at the highest dose level (Sousa et al., 

2002). 

7.2.2 Inhalation 

7.2.2.1 Hydrogen cyanide 

 No statistically significant increase in the incidence 

of histopathological changes in the lungs or cardiovascular tissues (e.g., myocardial ultrastructure) compared 

with the controls was noted in rabbits continuously 

exposed to 0.6 mg hydrogen cyanide/m3

 for 1 or 4 weeks 

(Hugod, 1981). 

 Dogs exposed to 50 mg hydrogen cyanide/m3

 for 

30 min every third day for 28 days exhibited extensive 

vascular and cellular central nervous system lesions, 

including vasodilation and haemorrhages (Valade, 

1952). 

7.2.2.2 Acetone cyanohydrin 

 Sprague-Dawley rats (10 per sex and dose level) 

were exposed to ACH in the atmosphere at average 

concentrations of 33, 106, or 211 mg/m3

 for 6 h/day, 

5 days/week, for 4 weeks. This was equivalent to 

hydrogen cyanide concentrations of 10, 34, and 

67 mg/m3

 (Monsanto Co., 1985c). On the first exposure 

day, the highest concentration of ACH in the chamber 

was 225 mg/m3

, corresponding to 71 mg hydrogen 

cyanide/m3

, and 3 out of the 10 males at the highest dose 

level died after the first exposure (see section 7.1). 

Irritation of the nose and eyes was observed at the two 

highest exposure levels. High-dose females had 

decreased blood haemoglobin and elevated blood urea 

nitrogen concentrations, and total serum protein levels 

were decreased in high- and mid-dose males; these 

laboratory changes were within the reference range. No 

gross or microscopic changes were observed in a wide 

range of organs at autopsy. No changes were observed in 

thyroid function, with the exception of an elevated T3

level in the mid-dose males. The NOAEL (the observed 

effect being irritation) reported from the study was 

33 mg ACH/m3

 (10 mg hydrogen cyanide/m3); this can 

be estimated to correspond to a daily dose of 2.7 mg 

cyanide/kg body weight per day.1

7.3 Medium-term exposure

7.3.1 Oral 

 In 13-week studies, groups of F344/N rats and 

B6C3F1 mice (10 of each sex) were administered 0, 3, 

10, 30, 100, or 300 mg sodium cyanide/litre in drinkingwater (NTP, 1993). The equivalent cyanide ion doses 

were 0, 0.2, 0.5, 1.4, 4.5, and 12.5 (in males) and 0, 0.2, 

0.5, 1.7, 4.9, and 12.5 (in females) mg cyanide/kg body 

weight per day for rats and 0, 0.3, 1, 3, 9, and 26 mg 

cyanide/kg body weight per day for mice. No deaths, 

clinically significant effects on body or organ weights, 

or histopathological or clinical pathology changes were 

noted in either rats or mice. In particular, no lesions were 

found in the brain or thyroid gland. Effects on the reproductive organs were analysed in animals in the three 

highest dose groups. A slight (7–13%) but statistically 

significant reduction was observed in sperm motility and 

in the weight of cauda epididymidis in all studied groups 

of male rats. In the males of the 300 mg/litre group 

(12.5 mg cyanide/kg body weight per day), a statistically 

significant decrease was observed in the weight of the 

left epididymis, left cauda epididymidis, left testis, and 

the number of spermatid heads per testis. Sodium cyanide at concentrations of 100 and 300 mg/litre (4.9 and 

12.5 mg cyanide/kg body weight per day, respectively) 

 

1

 Calculated with a minute volume of 150 ml/min and an 

average body weight of 200 g and assuming 100% absorption. 
Concise International Chemical Assessment Document 61 

20 

caused a statistically significant increase in the time 

spent by female rats in proestrus and diestrus relative to 

estrus and metestrus. In male mice, a statistically 

significant decrease in the left cauda epididymidis 

weights was noted at 26 mg cyanide/kg body weight per 

day, but no changes in sperm motility or spermatid head 

density were observed. No changes in the estrous cycle 

length in female mice were noted. The authors noted that 

the changes in male rats are consistent with a small but 

measurable adverse effect on reproduction. While these 

changes are insufficient to decrease fertility in rats, the 

relative sensitivity of humans to such changes is 

considered to be greater than that of rats; therefore, a 

potential for adverse reproductive effects exists in 

humans (NTP, 1993). One of the source documents 

(ATSDR, 1997) identified 12.5 mg cyanide/kg body 

weight per day as the lowest-observed-adverse-effect 

level (LOAEL), based on all the effects on reproductive 

organs observed in the male rats, and 4.5 mg cyanide/kg 

body weight per day as the NOAEL; the findings in 

female rats were not considered adverse (ATSDR, 

1997).1

 In a 13-week study, male Sprague-Dawley rats were 

administered potassium cyanide in drinking-water at a 

dose level of 40, 80, or 160/140 mg/kg body weight per 

day. These doses correspond to 16, 32, and 64/56 mg 

cyanide/kg body weight per day (Leuschner et al., 1989). 

Histopathological investigation of the brain, heart, liver, 

testes, thyroid, and kidneys did not reveal adverse 

effects. Urinary protein excretion was increased in dosed 

animals, and dose-dependent increases were observed in 

organ weights; these were interpreted to have arisen 

from decreased food and water consumption caused by 

decreased palatability.2

 All rats survived, but there was a dose-dependent 

loss of body weight, an increase in thyroid weight, and a 

decrease of blood haemoglobin and serum T4 levels in 

rats after 14 weeks on a diet containing 5 or 10 g 

potassium cyanide/100 g diet (corresponding to 

 

1 The German MAK Commission on occupational exposure 

limits also considered the isolated effects on cauda

epididymidis weight at the dose 1.4 mg cyanide/kg body 

weight as non-adverse and the more extensive changes 

observed at 12.5 mg cyanide/kg body weight as adverse. 

However, the MAK Commission considered the effects on the 

estrus cycle in female rats at 4.9 mg cyanide/kg body weight as 

adverse and thus set the NOAEL in rats at the lowest dose 

studied for this end-point (given as 1.7 mg cyanide/kg body 

weight in the original report, but as 1.6 mg cyanide/kg body 

weight in the German MAK report) (Greim, 2003).

2 In a kinetic study, apparently from the same experiment 

(Leuschner et al., 1991), it was noted that several animals at 

the highest dose died during the experiment; this was the 

reason why the dose was reduced from 160 to 140 mg/kg body 

weight per day at the beginning of week 12.

approximately 800 and 1600 mg cyanide/kg body weight 

per day) (Olusi et al., 1979). 

 In a 3-month study, weanling male Wistar rats were 

given potassium cyanide at 0, 0.15, 0.3, or 0.6 mg/kg 

body weight per day daily (0, 0.06, 0.12, and 0.24 mg 

cyanide/kg body weight per day) by gavage (SotoBlanco et al., 2002b). In plasma samples collected on the 

last day of the administration, no changes were observed 

in the concentrations of T3, T4, or glucose, while a 

decrease was observed in the concentration of cholesterol, significant at the highest dose (45%, P < 0.05). 

The authors made a qualitative statement that dosedependent neuropathological findings were observed, 

including spheroids on the ventral horn of the spinal 

cord, neuron loss in the hippocampus, damaged Purkinje 

cells, and loss of cerebellar matter. No further details or 

statistical analysis was presented. 

 No effects were noted in Sprague-Dawley rats fed 

potassium cyanide at concentrations up to 187.5 mg/100 

g diet (750 mg cyanide/kg diet) for 56 days. On proteindeficient diets, the lowest body weight gain was 

obtained at the highest dietary cyanide concentration 

(Tewe & Maner, 1985). 

 In a 40-week study in rabbits, the animals were fed 

potassium cyanide at a level of 1.76 g/kg diet (corresponding to 24–17 mg cyanide/kg body weight per day) 

(Okolie & Osagie, 1999). The weight gain of the treated 

animals was decreased by 33%; at the end of the 

experimental period, serum urea and creatinine levels 

were elevated, as were the activities of serum lactate 

dehydrogenase, sorbitol dehydrogenase, ALAT, and 

alkaline phosphatase.

 In a neuropathological study (Soto-Blanco et al., 

2002a), goats, 30–45 days old at the beginning of the 

study, were given potassium cyanide in milk (until 

weaning) and in drinking-water thereafter at a dose level 

of 0.3, 0.6, 1.2, or 3.0 mg (0.12, 0.24, 0.48, or 1.2 mg 

cyanide)/kg body weight per day for 5 months. In a 

qualitative morphological and immunohistochemical 

study, presence of gliosis and spongiosis in the medulla 

oblongata and spinal cord and gliosis in the pons and 

damage to Purkinje cells in the cerebellum were 

observed at the highest dose, but no increase in apoptotic 

cells was reported. Congestion and haemorrhage in the 

cerebellum were observed at the 0.48 mg cyanide/kg 

body weight per day group. No quantification or 

statistical analysis of the findings was presented. 

 Hyperactivity tremors, convulsions, and laboured 

breathing were noted in Sprague-Dawley rats exposed to 

7.8 mg cyanide/kg body weight per day as copper 

cyanide for 90 days by gavage. No similar effects were 

reported at 1.45 mg cyanide/kg body weight per day.

Laboured respiration occurred in rats exposed at a lower 
Hydrogen cyanide and cyanides: Human health aspects 

21 

dose of 0.8 mg cyanide/kg body weight per day when 

administered potassium silver cyanide for 90 days 

(Gerhart, 1987). 

 The only sign of toxicity observed in male rats 

exposed by gavage to copper cyanide (14.5 mg 

cyanide/kg body weight per day) (Gerhart, 1986) or 

potassium silver cyanide (2.6 mg cyanide/kg body 

weight per day) for 90 days was an increase in testis 

weight (Gerhart, 1987). No effects were observed in 

female rats in either study. The NOAELs were 4.35 mg 

cyanide/kg body weight per day (Gerhart, 1986) and 

0.8 mg cyanide/kg body weight per day (Gerhart, 1987). 

 Kamalu and co-workers (Kamalu & Agharanya, 

1991; Kamalu, 1993) compared the effects of cassava 

containing linamarin with those of a diet containing an 

equivalent amount of sodium cyanide in three groups 

of growing dogs, each comprising six animals, for 

14 weeks. One group was fed cassava (gari) as the 

carbohydrate source, which was expected to release 

10.8 mg hydrogen cyanide/kg cooked food; another 

group was fed on the control diet with rice as the 

carbohydrate source, to which enough sodium cyanide 

was added at feeding time to release 10.8 mg hydrogen 

cyanide/kg cooked food (for both, the daily dose was 

1.08 mg hydrogen cyanide/kg body weight). The control 

group was fed this rice diet without added sodium 

cyanide. Nephrosis and changed plasma free amino acid 

profile were observed in the sodium cyanide-treated 

group, while no effect was observed in the plasma 

glutamyltransferase, ALAT, or isocitrate dehydrogenase 

activities or in the histology of the liver, kidney, or 

myocardium. Adrenal hyperplasia and hypertrophy and 

pancreatic necrosis and fibrosis were observed. (In 

contrast, the gari diet caused generalized congestion and 

haemorrhage, periportal vacuolation of the liver, 

swelling, vacuolation, and rupture of the epithelial cells 

of the proximal convoluted tubule of the kidney, 

myocardial degeneration, adrenal gland degeneration, 

and pancreatic haemorrhage, necrosis, and fibrosis.) A 

36% decrease in the serum T3 concentration was noted, 

together with histological changes of the thyroid 

consistent with parenchymatous goitre. A significantly 

reduced frequency of testicular tubules in stage 8 of the 

spermatogenic cycle as well as marked testicular germ 

cell sloughing and degeneration were also observed. 

7.3.2 Inhalation 

7.3.2.1 Cyanogen 

 Groups of 30 male albino rats (Charles River) were 

each exposed for 6 months (6 h/day, 5 days/week) by 

inhalation to 0, 24, or 54 mg cyanogen/m3 (corresponding to 0, 25, and 56 mg hydrogen cyanide/m3

). There 

were no effects on haematological or clinical chemistry 

parameters, gross pathology, or histopathology (liver, 

kidney, cardiovascular system) attributable to the 

cyanogen exposure. Body weights were significantly 

lower in rats exposed to 54 mg cyanogen/m3

 than in the 

controls (Lewis et al., 1984). 

 In an inhalation study, groups of five rhesus monkeys (Macacca mulatta) were exposed to 24 or 54 mg 

cyanogen/m3

 for 6 h/day, 5 days/week, for 6 months. 

This corresponded to 25 and 56 mg hydrogen cyanide/m3

. There were no effects on haematological or 

clinical chemistry parameters attributable to the inhalation exposure. Total lung moisture content was significantly lower in both treatment groups than in control 

animals (Lewis et al., 1984). 

7.3.2.2 Acetone cyanohydrin 

 Sprague-Dawley rats (15 per sex and dose level) 

were exposed to ACH at concentrations of 0, 36, 101, or 

204 mg ACH/m3

, 6 h/day, 5 days/week, for 14 weeks. 

The exposures were equivalent to 0, 11, 32, and 65 mg 

hydrogen cyanide/m3

 (Monsanto Co., 1984a). There 

were no treatment-related deaths or significant changes 

in body weight gain or haematology. Irritation of the 

nose and eyes was observed, but no more in exposed 

than in non-exposed animals. A decrease in blood 

glucose was recorded in high- and mid-exposure 

females, and a decrease in total serum protein and 

globulin concentrations was noted in the mid- and lowdose females. A comprehensive microscopic evaluation 

of tissues revealed no abnormalities, and no changes in 

serum T3 or T4 levels were observed. The NOAEL 

reported from the study was 204 mg ACH/m3

, 

corresponding to 65 mg hydrogen cyanide/m3

. This can 

be estimated to correspond to a daily dose of 15 mg 

cyanide/kg body weight per day.1

 In the male fertility study described in section 7.6.1, 

no mortality, clinical signs of toxicity, changes in body 

weight, or changes in gross necropsy were observed 

after 48 exposures to up to 202 mg ACH (64 mg hydrogen cyanide)/m3

, 6 h/day, 5 days/week (Monsanto Co., 

1985a). 

 In the female fertility study described in section 

7.6.1, there was a dose-dependent increase in red nasal 

discharge of encrustation, but no other clinical signs of 

toxicity, mortality, changes in body weight, or changes 

in gross necropsy during or after 34–36 exposures to up 

to 207 mg ACH (66 mg hydrogen cyanide)/m3

, 6 h/day, 

7 days/week (Monsanto Co., 1985b). 

 

1

 Calculated with a minute volume of 175 ml/min and an 

average body weight of 275 g and assuming 100% absorption. 
Concise International Chemical Assessment Document 61 

22 

7.4 Long-term exposure 

 Few data exist on the effects of chronic cyanide 

exposure. In a 2-year dietary study, weanling albino rats 

(10 per sex per group) were administered food fumigated 

with hydrogen cyanide (special jars were used in order 

to limit volatilization of hydrogen cyanide from the feed) 

(Howard & Hanzal, 1955). The average concentrations 

of cyanide in the feed were 0, 73, and 183 mg/kg diet, as 

estimated (US EPA, 1993b) based on the authors’ data 

for concentrations at the beginning and end of each food 

preparation and by assuming a first-order rate of loss for 

the intervening period and on the corresponding daily 

doses of 4.3 and 10.8 mg cyanide/kg body weight per 

day. No treatment-related effects on survival or growth 

rate, signs of toxicity, or haematological or histopathological changes in the organs examined (heart, lung, 

liver, spleen, gastrointestinal tract, kidneys, adrenals, 

thyroid, testes, uterus, ovaries, cerebrum, cerebellum, 

and brain) were observed in the treated male or female 

animals. A NOAEL of 10.8 mg cyanide/kg body weight 

per day was established. 

 The effects of cyanide on thyroid function were 

investigated in groups of 10 male weanling rats fed a 

semipurified casein-based diet for 11.5 months either 

supplemented by added methionine, vitamin B12, and 

potassium iodide or without added vitamin B12 and 

potassium iodide and with the methionine addition 

restricted to a third. Both dietary groups were divided 

into three: one served as the control, the second received 

1500 mg potassium cyanide/kg, and the third received 

2240 mg potassium thiocyanate/kg. The rats given the 

potassium cyanide would have received doses of 30 mg 

cyanide/kg body weight per day. Cyanide, but not 

thiocyanate, caused a consistent reduction in weight gain 

in the complete and restricted diet fed animals. Both 

cyanide and thiocyanate caused decreased thyroid gland 

activity in young rats, particularly in those fed the 

restricted diet. Depression of both plasma T4 and the T4

secretion rate, suggestive of depressed thyroid function, 

was found at 4 months, but to a lesser degree after 

1 year. At autopsy, the animals were found to have 

enlarged thyroids, which suggested a mechanism of 

adaptation (Philbrick et al., 1979). 

 In order to study the possible contribution of 

cyanide exposure to malnutrition-related diabetes 

mellitus (see section 8), Okolie & Osagie (1999, 2000) 

fed New Zealand White rabbits potassium cyanide for 

10 months (702 mg cyanide/kg diet, corresponding to 

approximately 20 mg/kg body weight per day). No 

effects were observed on the serum amylase activity, 

blood glucose concentration, or the morphology of the 

pancreas, while degenerative changes were reported in 

the liver and kidney. Similarly, 1-year feeding of cassava 

to rats induced no changes in blood glucose homeostasis 

or pancreatic histology (Mathangi et al., 2000). 

 Because of the small group size and limited 

exposure time in most of them, these studies are not 

informative with regard to the possible carcinogenicity 

of cyanides.

7.5 Genotoxicity and related end-points 

 Sodium cyanide was not mutagenic in Salmonella 

typhimurium strains TA100, TA1535, TA97, or TA98 

with or without exogenous metabolic activation (NTP, 

1993). Potassium cyanide was not mutagenic in five 

strains (TA1535, TA1537, TA1538, TA98, and TA100) 

of S. typhimurium with or without metabolic activation 

(De Flora, 1981). Hydrogen cyanide induced mutations 

in S. typhimurium TA100 in the absence of S9 activation, but was not mutagenic to strain TA98 with or 

without S9 activation (Kushi et al., 1983). ACH did not 

induce mutations in S. typhimurium strains TA1535, 

TA1537, TA1538, TA100, or TA98 in a plate incorporation assay or at concentratons of 100–950 μg/ml in a 

CHO/HGPRT assay (Monsanto Co., 1983b,c). 

 DNA repair tests in Escherichia coli WP67, 

CM871, and WP2 with potassium cyanide were negative 

(De Flora et al., 1984). Potassium cyanide induced both 

time- and dose-dependent DNA fragmentation accompanied by cytotoxicity in rat thymocytes in vitro. 

Cyanide also induced DNA damage in baby hamster 

kidney cells (BHK-21) in vitro, where, unlike thymocytes, internucleosome DNA fragmentation was not 

observed (Bhattacharya & Rao, 1997). The cytotoxic 

mode of double strand breaks in the pathogenesis of 

DNA fragmentation was studied by Vock et al. (1998), 

employing an A549 human epithelial-like lung carcinoma cell line treated with potassium cyanide. Induction 

of double strand breaks by potassium cyanide was 

observed only after cell viability was reduced to less 

than 60%, indicating that double strand breaks were the 

consequence of extragenomic damage, as a secondary 

effect of high cytotoxicity in combination with cell 

lethality. 

 Sodium cyanide was a highly effective inducer of 

germline aneuploidy in Drosophila (Osgood & Sterling, 

1991). 

 No statistically significant increases in the frequency of chromosomal aberrations or changes in 

mitotic index compared with control values were found 

in bone marrow cells from four groups of 24 male and 

24 female Sprague-Dawley rats administered a single 

dose of ACH by oral gavage at levels of 0, 1.5, 5, or 

15 mg/kg body weight with preparation intervals of 6, 

12, and 24 h post-administration (Monsanto Co., 1984b). 

 No testicular DNA synthesis inhibition was detected 

in mice after a single oral potassium cyanide dose of 

1 mg/kg body weight (Friedman & Staub, 1976). 
Hydrogen cyanide and cyanides: Human health aspects 

23 

7.6 Reproductive and developmental 

toxicity 

 Relatively few data are available on the reproductive and developmental toxicity of cyanides. No reproductive and developmental toxicity studies are available 

for hydrogen cyanide. 

7.6.1 Effects on fertility 

 After 2 weeks on a diet containing 5 or 10 g 

potassium cyanide/100 g diet, female rats (10 per group) 

were mated with untreated males. No pregnancies 

resulted. The dose corresponds roughly to 1000 and 

2000 mg cyanide/kg body weight per day (Olusi et al., 

1979). There was a dose-dependent decrease in body 

weight gain, blood haemoglobin (18% and 23%), and 

serum T4 concentration (54% and 75%). 

 In a male fertility study (Monsanto Co., 1985a), 

Sprague-Dawley rats (n = 15) were exposed by inhalation to ACH (0, 35, 101, or 202 mg/m3

; 0, 11, 32, or 

64 mg hydrogen cyanide/m3

), 6 h/day, 5 days/week, 

during a period of 69 days (i.e., 48 exposure days). After 

the treatment period, the males were mated with three 

non-exposed females each. There were no effects on the 

mean body weight, clinical signs of toxicity, or anatomical changes in gross necropsy. The mating efficiency, 

number of live implants, and pre- and post-implantation 

losses were not different between treated and control 

groups. 

 Female Sprague-Dawley rats were exposed by 

inhalation (6 h/day, 7 days/week) for 21 days to ACH at 

at 38, 108, or 207 mg/m3

 and then mated with untreated 

males. Exposure of the females, which was equivalent to 

12, 34, and 66 mg hydrogen cyanide/m3

, was continued 

until the day of mating, and the females were sacrificed 

at mid-gestation (gestation days 13–15). No treatmentrelated effects on female fertility were observed in any 

of the exposure groups. The only frequently observed 

clinical sign post-exposure was red nasal discharge or 

encrustation. The highest exposure in the study could be 

considered as the no-observed-effect level (NOEL) for 

female reproductive effects (Monsanto Co., 1985b). 

7.6.2 Developmental toxicity 

 Preliminary experiments with pregnant Golden 

Syrian hamsters showed that at a dose rate of 

0.125 mmol/kg body weight per hour, no effects on 

the fetus were observed, while at a dose rate of 

0.133 mmol/kg body weight per hour or more, there was 

a 100% resorption rate and maternal deaths. Toxicity to 

dams increased with increasing dose levels and included 

shortness of breath, incoordination, reduced body temperature, and loss of body weight. Co-administration of 

thiosulfate eliminated the teratogenic effect, protecting 

the dams and fetuses from the toxic effects of cyanide 

(Doherty et al., 1982). In a follow-up experiment, 

pregnant Golden Syrian hamsters (5–7 animals per 

group) were continuously exposed to sodium cyanide 

from day 6 to day 9 of gestation at 0, 0.126, 0.1275, or 

0.1295 mmol/kg body weight per hour by using osmotic 

minipumps implanted subcutaneously. These doses are 

equivalent to 0, 3.28, 3.32, and 3.37 mg cyanide/kg body 

weight per hour or 0, 78.7, 79.6, and 80.9 mg/kg body 

weight per day. The treatment induced a remarkable 

increase in resorptions as well as fetal malformations. 

These included non-closure of the neural tube, exencephaly, encephalocoele, and malformations of the heart 

and limbs or tail (Doherty et al., 1982). 

 Pregnant Wistar rats (10 animals per group) were 

fed a cassava diet liberating 21 mg hydrogen cyanide/kg

diet, fortified with 500 mg potassium cyanide/kg diet, 

throughout gestation and lactation. This is equivalent to 

an estimated daily dose of 16 mg cyanide/kg body 

weight. No effects were observed on the number, 

mortality at birth, or body weight of offspring or weight 

gain of pups during lactation (Tewe & Maner, 1981a). 

 In equivalent studies with pregnant Yorkshire pigs, 

three groups of six animals were given potassium 

cyanide in the diet (30.3, 277, or 521 mg cyanide/kg 

diet)1 throughout gestation. No effects were seen on the 

number or weight of offspring or subsequent lactational 

performance. Pregnant sows treated at the highest dose 

level had proliferative changes in the kidney glomeruli 

and increased thyroid weights. Fetal spleen to body 

weight and head to body weight ratios in the highcyanide group were significantly reduced (P > 0.05) 

compared with the low-cyanide exposed group (Tewe & 

Maner, 1981b). 

 In a preliminary study with limited experimental 

details, pregnant albino rats were fed milled cassava 

powder as 50% and 80% of their diet during the 15 days 

of gestation. Growth retardation and an increased 

frequency of resorptions were observed at both dose 

levels; in addition, limb defects were observed at the 

high dose. The weight gain of the dams was lowered; no 

further information on maternal toxicity was given. No 

indication of the cyanide content of the cassava diet was 

given. The effects observed may have resulted from 

nutritional deficiencies, such as the low protein content 

of cassava (Singh, 1981). 

 Groups of pregnant hamsters were fed diets 

consisting of two types of cassava meal, either a “lowcyanide” (sweet cassava meal) or a “high-cyanide” 

(bitter cassava meal) variety. These were mixed (80:20) 

 

1 From the weight of the gilts and the daily feed intake, it can 

be roughly estimated that the daily dose of cyanide was 1, 7, 

and 19 mg/kg body weight.
Concise International Chemical Assessment Document 61 

24 

with laboratory chow and administered on days 3–14 of 

gestation. The cyanide concentration of the sweet 

cassava meals was 0.6–0.7 mmol/kg; that of the bitter 

cassava meal was 5–11 (mean 7.9) mmol/kg.1 Cassavafed dams gained significantly less weight than did 

control animals (fed diet similar in nutritional value as 

cassava, but without cyanogenic glycosides), and their 

offspring showed evidence of fetotoxicity (reduced fetal 

body weight and reduced ossification of sacrocaudal 

vertebrae, metatarsals, and sternebrae). The bitter 

cassava also produced a significant increase in the 

number of runts compared with litters from dams fed 

either low-protein2 or laboratory-stock diets. The only 

teratogenic effects noted were hydrocephalus in three 

animals in the low-cyanide (sweet cassava) test group 

and one encephalocoele found in one animal in the highcyanide (bitter cassava) test group (Frakes et al., 1986b). 

 In a teratogenicity study, hamsters were given a 

single oral dose of linamarin (0, 70, 100, 120, or 

140 mg/kg body weight, corresponding to 0, 7.4, 11, 13, 

or 15 mg cyanide/kg body weight per day) on day 8 of 

the pregnancy. The animals were killed on day 15 of the 

pregnancy, and the numbers of resorption sites, dead 

fetuses, and living fetuses were recorded. Living fetuses 

were examined for gross external malformations and for 

internal malformations using histopathological methods. 

Linamarin had no effect on fetal body weight, ossification, embryonic mortality, or litter size. At the two 

highest doses, which caused overt maternal toxicity 

(dyspnoea, hyperpnoea, ataxia, tremor, and hypothermia), vertebral and rib anomalies and encephalocoeles were observed (Frakes et al., 1985). 

 A single oral dose of D,L-amygdalin at gestational 

day 8 resulted in exencephaly, encephalocoele, and 

skeletal malformations at doses of ≥250 mg/kg body 

weight (≥14 mg cyanide/kg body weight) in hamsters 

(these doses were also clearly toxic to the mothers). At 

the lowest dose tested, 200 mg/kg body weight (11 mg 

cyanide/kg body weight), fused ribs were observed in 

two offspring of one mother (maternal toxicity not 

reported). Encephalocoele and rib anomalies were also 

observed after a dose of D-prunasin (177 mg/kg body 

weight [16 mg cyanide/kg body weight]) in the absence 

of maternal toxicity in hamsters. No teratogenic effects 

were noted when hamsters received D,L-amygdalin 

(275 mg/kg body weight [16 mg cyanide/kg body 

weight]) intravenously (Willhite, 1982). The teratogenic 

effects found were considered to be due to cyanide 

 

1 If the hamsters weighed 110 g at the beginning of the experiment, this would lead to a daily dose of cyanide of 1 and 

15 mg/kg body weight in the sweet and bitter cassava groups, 

respectively.

2 Diet formulated to simulate the cassava diet with a low (4%) 

protein content, in contrast to the 25% protein content in the 

standard laboratory diet.

released by bacterial β-glucosidase in the gastrointestinal 

tract (Willhite, 1982).

 Groups of 25 pregnant Sprague-Dawley rats were 

dosed by gavage on days 6–15 of gestation with 0, 1, 3, 

or 10 mg ACH/kg body weight (equivalent to 0, 0.3, 0.9, 

or 3 mg cyanide/kg body weight). Maternal toxicity was 

evidenced by slight reductions in body weight gain in 

the mid- and high-exposure groups, and statistically 

significant differences between the high-dose group and 

controls were found for the number of corpora lutea 

implantations per dam. There were no comparable 

differences in the number of viable fetuses per dam, 

post-implantation losses per dam, mean fetal body 

weight, or fetal sex distribution for all dose groups and 

the controls. The incidences of fetal malformations and 

developmental variations for all fetuses of treated 

animals and controls were also comparable. It was 

concluded that 10 mg ACH/kg body weight (3 mg 

cyanide/kg body weight) was not teratogenic in the rat in 

the presence of maternal toxicity (Monsanto Co., 1982, 

1983a). 

7.7 Neurotoxicity 

 The effects of cyanide on behaviour were studied in 

fasted 25-week-old miniature pigs (12 litter mates: 

5 females and 7 castrated males) randomized in four 

groups. The animals were dosed daily for 24 weeks with 

a single bolus of cyanide as aqueous potassium cyanide 

just prior to the daily feeding. The doses were 0, 0.4, 0.7, 

or 1.2 mg cyanide/kg body weight, chosen to be equivalent to those consumed by West Africans in their diet 

(Jackson et al., 1985). Every 6 weeks, thyroid function 

(T3 and T4) and fasting blood glucose were measured, 

but not thyroid-stimulating hormone (TSH). Daily 

observations were made of clinical signs and various 

behavioural measurements, including social, antagonistic, exploratory, learning, feeding, and excretory 

behaviour. In all treatment groups, dose-related 

decreases were evident from week 6 in blood levels of 

T3 and T4, and an increase in fasting blood glucose was 

noted, particularly in top-dose animals. Statistical 

analysis was not provided for each dose group versus 

control, but changes in top-dose animals appeared 

significant by week 18; by week 24, decreases of 35% 

for T3 and 15% for T4 and an increase of 60% in fasting 

blood glucose were observed. Behavioural observations 

revealed a picture of decreased high energy-demanding 

behaviour, such as exploration and aggression, slower 

eating, more frequent drinking, and shivering consistent 

with the decreased thyroid activity. A LOAEL of 

1.2 mg/kg body weight per day could be suggested from 

this study (Jackson, 1988). 

 Dogs administered sodium cyanide in capsules at 

levels of 0, 0.5, 2, or 1–4 mg/kg body weight (one dog at 

each dose level) daily for 13–15 months showed severe 
Hydrogen cyanide and cyanides: Human health aspects 

25 

signs of acute cyanide poisoning right after the daily 

dosing (the dog at the lowest dose died). In the autopsy, 

the only significant findings were degenerative changes 

in ganglia cells of the central nervous system, interpreted 

to be caused by multiple episodes of acute cerebral 

hypoxia (Hertting et al., 1960). 

 Transient behavioural changes in monkeys but not 

in rats exposed for 6 months to 54 mg cyanogen/m3

 have 

been reported (Lewis et al., 1984). 

 Potentiation to noise-induced hearing loss by 

exposure of rats to low concentrations of hydrogen 

cyanide was reported by Fechter et al. (2002). It was 

suggested that hydrogen cyanide (34 mg/m3

 for 3.5 h) 

plus noise produced impaired auditory function by 

producing significant oxidative stress in the cochlea. 

Hydrogen cyanide alone did not cause significant 

hearing loss or hair cell loss. 

 A single intraperitoneal dose and 25 repeated 

intraperitoneal doses of sodium cyanide (2 mg/kg body 

weight [1 mg cyanide/kg body weight]), stated to represent 25% of the LD50, administered to Wistar strain 

albino rats resulted in similar reductions of memory (Tmaze test), along with reductions in the levels of 

dopamine and 5-hydroxytryptamine and increases in 

norepinephrine and epinephrine levels in the hippocampus, measured after a month of treatment (Mathangi & 

Namasivayam, 2000). 

7.8 Irritation and sensitization 

 Local effects of cyanides on the eye are demonstrated by conjunctival hyperaemia with mild chemosis, 

lacrimation, photophobia, and tingling sensation (IPCS, 

1992). No information was located on the sensitizing 

capacity of cyanides. 

7.9 Mode of action 

 As a respiratory poison, free cyanide (hydrogen 

cyanide or cyanide ion) has high acute toxicity due to its 

primary toxic effect of inhibiting cytochrome oxidase 

(by binding haem iron), the terminal enzyme of the 

mitochondrial electron transport chain (Isom & Way, 

1974). Tissue utilization of oxygen is impaired, and, 

with time, a state of histotoxic anoxia occurs (oxidative 

metabolism is brought to complete cessation). Cyanide 

can also inhibit approximately 40 enzymes, including a 

number of other important metalloenzymes containing, 

for the most part, iron, copper, or molybdenum (e.g., 

alkaline phosphatase, carbonic anhydrase, catalase, 

peroxidase, ascorbic acid oxidase, xanthine oxidase, and 

succinic dehydrogenase); these reactions may also 

contribute to cyanide toxicity (Rieders, 1971; Ardelt et 

al., 1989; US EPA, 1990; ATSDR, 1997). 

 Due to its high dependency on oxidative metabolism 

and limited anaerobic capacity, the central nervous 

system is particularly vulnerable to cyanide intoxication 

(Way, 1984). The central nervous system symptoms 

observed in cyanide toxicity parallel those observed 

following accumulation of calcium in the brain. Potassium cyanide also alters calcium homeostasis in a 

neuronal model, the PC-12 cell, and cytosolic calcium 

ion overload has been implicated as an intracellular 

mediator of cellular injury during and after anoxic 

hypoxia (Maduh et al., 1988; Pettersen & Cohen, 1993).

 Hydroperoxide generation with subsequent 

peroxidation of lipids and subsequent changes in 

structure and function of certain membranes have been 

suggested as a possible further mechanism of cyanide 

toxicity (Ardelt et al., 1989). 

 A number of animal and human cyanide and 

cyanogenic glycoside toxicological studies have cited 

evidence of poor diet, low protein, and vitamin B12 and 

folic acid deficiencies and suggested that these factors 

may have confounded or exacerbated the observed 

toxicities. Although the role of vitamin B12 deficiency, 

for example, has not been fully elaborated, it has been 

suggested that vitamin B12 may be a protective factor in 

cyanide neurotoxic effects. Experimentally, vitamin B12

restriction is hypothesized to sensitize the animal to 

cyanide toxic reactions (Philbrick et al., 1979). One 

study has demonstrated depletion of stores of proteinbound cobalamin in cyanide-treated animals, and it is 

theoretically possible that cyanide exposure might 

“chelate” vitamin B12, leading to its eventual depletion 

and to secondary folate effects (Blanc et al., 1985). 

8. EFFECTS ON HUMANS 

8.1 General population 

8.1.1 Exposure to cyanides

 The dose–effect curve of the acute effects in 

humans is steep. Whereas slight effects occur at 

exposure to hydrogen cyanide levels of 20–40 mg/m3

, 

50–60 mg/m3

 can be tolerated without immediate or late 

effects for 20 min to 1 h, 120–150 mg/m3

 is dangerous to 

life and may lead to death after 0.5–1 h, 150 mg/m3

 is 

likely to be fatal within 30 min, 200 mg/m3

 is likely to 

be fatal after 10 min, and 300 mg/m3

 is immediately 

fatal. It should be emphasized that this represents crude 

average exposure estimates, based on various studies 

(DECOS, 2002). 
Concise International Chemical Assessment Document 61 

26 

 A fire fatalities study in Maryland, USA, covering 

mostly residential fires over a 6-year period during 

which 523 fire fatalities occurred as a result of 392 fires, 

was reported by Birky & Clarke (1981). Although the 

predominant cause of death was attributed to carbon 

monoxide, toxic levels of hydrogen cyanide were found 

in the blood of a substantial percentage of the victims. A 

study of blood cyanide and carboxyhaemoglobin 

concentrations in 18 victims found dead in buildings 

after fires indicated that 50% of the victims had been 

exposed to toxic levels of hydrogen cyanide and 90% to 

toxic levels of carbon monoxide (Lundquist et al., 1989). 

Eighty-eight per cent of the fatalities in fire deaths in 

Glasgow, Scotland, during the period 1976–1979 had 

elevated blood cyanide levels; 31% had toxic levels of 

cyanide, and 12% would have shown severe cyanide 

poisoning (Anderson & Harland, 1982). Alarie (2002) 

reviewed the carboxyhaemoglobin and cyanide in blood 

of fire and non-fire victims resulting from 15 major 

episodes during the years 1971–1990 in France, the 

USA, and the United Kingdom. Analysis revealed that 

hydrogen cyanide is likely to be present in appreciable 

amounts in the blood of fire victims in modern fires. A 

review of the resultant mechanism of action of acute 

carbon monoxide and cyanide exposure and how they 

may interact concluded that it remains difficult to 

attribute death in fires to inhalation of hydrogen cyanide 

per se, given the complexity of interactions of smoke 

components (principally carbon monoxide). 

 Acute exposure to cyanide has occurred most 

frequently by the oral route from attempted suicides and 

homicides by ingestion of sodium or potassium cyanide 

or by accidental poisonings due to ingestion of apricot 

kernels or almond seeds (Rieders, 1971; NIOSH, 1976; 

US EPA, 1990; ATSDR, 1991; Alarie, 2002). Based on 

analyses of cyanide contents in tissues and in gastrointestinal tract contents among fatal (oral) poisoning 

cases (and comparative kinetics with dogs), Gettler & 

Baine (1938) estimated that death occurred after absorption of an average of 1.4 mg hydrogen cyanide/kg body 

weight; the lowest fatal absorbed dose was 0.54 mg 

hydrogen cyanide/kg body weight. In most poisoning 

cases, a large part of the ingested cyanide remained in 

the gastrointestinal tract (thus, using the dose ingested as 

an indicator of the lethality of cyanide is misleading). 

Some individuals ingesting 1–3 g of cyanide salts have 

survived (ATSDR, 1991). 

 The effects of acute cyanide exposure are dominated 

by central nervous system and cardiovascular disturbances (ATSDR, 1991). Typical signs of acute cyanide 

poisoning include tachypnoea, headache, vertigo, lack of 

motor coordination, weak pulse, cardiac arrhythmias, 

vomiting, stupor, convulsions, and coma (Ballantyne, 

1983b; Way, 1984; Johnson & Mellors, 1988). Pathological findings may include tracheal congestion with 

haemorrhage, cerebral and pulmonary oedema, gastric 

erosions, and petechiae of the brain meninges and 

pericardium (Way, 1984). Sequelae of severe acute 

cyanide exposure may also include Parkinson-like 

syndromes and cardiovascular signs of delayed posthypoxic myocardial lesions, as well as neuropsychiatric 

manifestations similar to those seen with post-hypoxic 

post-carbon monoxide encephalopathy (Uitti et al., 1985; 

Carella et al., 1988; Kadushin et al., 1988; ATSDR, 

1991). 

 Dermal absorption of hydrogen cyanide is much 

slower than pulmonary absorption, and the amount and 

speed of absorption through human skin are dependent 

on the amount of skin moisture and duration of skin 

contact (see also section 6.1). An average LD50 value for 

dermal exposure of 100 mg/kg body weight was estimated for humans (Rieders, 1971). Concentrations of 

7000–12 000 mg/m3

 were estimated to be fatal after a 5-

min exposure of workers with self-contained respirators 

without effective skin protection (Minkina, 1988). 

 Even healthy individuals have a small amount of 

cyanide in their bodies; concentrations up to 50 μg/100 g 

tissue have been found in different organs. A survey of 

plasma cyanide levels in 10 cases showed a maximum 

level of 106 μg/litre, with a mean of 48 μg/litre. The 

presence of cyanides in the plasma among “nonexposed” people has been variously attributed to factors 

including the breakdown of cyanogenic foods, vitamin 

B12, and heavy smoking (Ansell & Lewis, 1970). 

 No additive or synergistic effect was observed in the 

fatalities between cyanide and other factors, such as 

carbon monoxide, alcohol, age of victims, and presence 

of heart disease (US EPA, 1990). 

 Among patients with a serious hypertensive disease, 

intravenous administration of sodium nitroprusside was 

reported to lead to lowered serum T4 levels in approximately two-thirds of the patients; this effect became 

apparent at serum thiocyanate levels in excess of 

approximately 18 mg/litre, which was reported to 

correspond approximately to a daily dose of 200 mg 

sodium nitroprusside (20 mg cyanide) (Bödigheimer et 

al., 1979). Elevation of cyanide levels in blood was 

observed in patients receiving more than 2 μg nitroprusside/kg body weight per hour intravenously (Schultz 

et al., 1982). 

 Cyanide in tobacco smoke together with large 

amounts of alcohol and malnutrition have been proposed 

as culprits in tobacco–alcohol amblyopia, a syndrome at 

present seldom seen in Western countries, but still 

occasionally reported elsewhere (Solberg et al., 1998). 
Hydrogen cyanide and cyanides: Human health aspects 

27 

8.1.2 Food containing cyanogenic glycosides 

 Although acute cassava poisoning — sometimes 

leading to the death of whole families — has been 

occasionally reported after the consumption of inadequately processed cassava (Osuntokun, 1981; Cliff & 

Countinho, 1995), a much larger literature is available 

on the effects of long-term exposure to food containing 

cyanogenic glycosides. Clinical signs are often confounded by dietary deficiencies, including lack of 

protein, iodine, and vitamin B12. 

 Accidental poisonings have been reported in children (and, exceptionally, in adults) who had ingested 

apricot kernels or seeds or candy made from apricot 

kernels containing D,L-amygdalin, which, after hydrolysis, yields cyanide (Sayre & Kaymakcalan, 1964; Lasch 

& El Shawa, 1981; Suchard et al., 1998). Presumably 

because of lower body weight, children are especially 

vulnerable, with several fatal poisonings occurring after 

they had consumed apricot seeds. It has been estimated 

that, depending on the total cyanogenic potential of 

apricot seeds, 10 or more seeds could be fatal to a child 

(Nahrstedt, 1993). 

 Accidental choke cherry poisonings (attributed to 

D,L-amygdalin) have also been reported (Pijoan, 1942; 

Pentore et al., 1996). Pentore et al. (1996) described a 

case of a 56-year-old woman in Italy who was accidentally poisoned when she ingested choke cherries whose 

pulp contained cyanide (amygdalin). After recovery 

from coma, the patient showed signs resembling 

Parkinson disease, retrobulbar neuritis, and sensorimotor 

neuropathy. The choke cherries showed cyanide levels 

ranging from 4.7 to 15 mg/kg in the cherries and from 43 

to 45 mg/kg in the spirit. The quantity of cyanide was 

reported to depend on the ripeness of the cherries and the 

year in which they were harvested. 

 Consumption of food containing cyanogenic glycosides has been linked to several different diseases affecting mainly the nervous system, such as tropical ataxic 

neuropathy in Nigeria, spastic paraparesis (called mantakassa in Mozambique and konzo in the Democratic 

Republic of the Congo) in Cameroon, Central African 

Republic, Mozambique, Tanzania, and the Democratic 

Republic of the Congo (formerly Zaire), as well as 

retrobulbar neuritis and optic atrophy associated with 

pernicious anaemia. Cyanides have also been implicated 

in tobacco–alcohol amblyopia and thyroid effects such 

as goitre and even cretinism (Osuntokun et al., 1969; 

Ermans et al., 1972; Makene & Osuntokun, 1972, 1980; 

Wilson, 1972, 1983; Howlett et al., 1990; US EPA, 

1990; ATSDR, 1991; Tylleskär et al., 1994; Boivin, 

1997; Lantum, 1998; Ernesto et al., 2002). 

 Tropical ataxic neuropathy, an upper motor neuron 

disease characterized by irreversible paraparesis 

(Ernesto et al., 2002), was described in Nigeria in the 

1930s, and dietary cassava was proposed to be the 

causative factor in 1934. The essential neurological 

components of the disease are myelopathy, bilateral 

optic atrophy, bilateral perceptive deafness, and polyneuropathy. The peak incidence is in the 5th and 6th 

decades of life, and the disease occurs rarely in children 

under 10 years of age. Patients usually give a history of 

almost total dependence on a monotonous diet of 

cassava derivatives. The plasma thiocyanate level in 

patients within 48 h of admission to hospital was 113 ± 

0.2 μmol/litre, while in the referents it was 2.4 ± 0.15 

μmol/litre (Osuntokun, 1981). However, the role of 

cyanide exposure as the only causative agent in tropical 

neuropathy is made questionable by the finding that 

when comparing two villages in Nigeria, one with a high 

prevalence (490/10 000) of tropical ataxic neuropathy 

and another with a low prevalence (17/10 000) (giving 

an age-adjusted prevalence ratio of 4), the estimated 

intake of cassava foods was higher in the latter, and no 

difference was observed in the urinary thiocyanate 

excretion between the two villages (Oluwole et al., 

2002). 

 An epidemic of spastic paraparesis occurred in a 

drought-stricken cassava staple area of Mozambique in 

1981–1982. Altogether, 1102 cases were identified. The 

highest recorded village prevalence rate found by active 

case detection was 29 per 1000 inhabitants; 65% of the 

cases were under 15 years of age. In contrast to tropical 

neuropathy, the onset of mantakassa was acute. General 

symptoms around the time of onset included fever, pain 

(especially in the legs), paraesthesiae, headache, dizziness, and vomiting; many patients also complained of 

weakness in the arms and difficulty in speaking and in 

seeing. Some mothers said that their children had difficulty in hearing. Neurological investigation revealed 

symmetrical spastic paraparesis of the lower extremities, 

symmetrically increased upper limb reflexes, diminished 

visual acuity, and dysarthria. Some of the patients had 

sensory changes as well. The mean hydrogen cyanide 

contents (mg/kg) of cassava from the affected area were 

as follows: fresh bitter cassava leaves, 377; fresh sweet 

cassava leaves, 347; fresh bitter cassava roots, 327; fresh 

sweet cassava roots, 138; dried bitter cassava roots, 95; 

dried sweet cassava roots, 46; cassava flour, 40; and 

cooked cassava, 10. The estimated intake of cyanide was 

14–30 mg/day. The mean thiocyanate level in 246 specimens of blood and serum from patients from the whole 

area was 330 μmol/litre. In the village with the most 

patients, the mean thiocyanate level among the patients 

was 324 ± 18 μmol/litre, while 22 controls from this 

village showed serum thiocyanate levels of 288 ± 23 

μmol/litre. There was no correlation between the disease 

severity and serum thiocyanate level. Also, because of 

the drought, there was a general lack of food, specifically of protein-rich food, with many cases of 
Concise International Chemical Assessment Document 61 

28 

kwashiorkor1 appearing in February 1982 (Ministry of 

Health, Mozambique, 1984a,b). 

 Outbreaks of konzo have been reported in the 

Democratic Republic of the Congo (formerly Zaire)

since 1938. The outbreaks have occurred during 

droughts and dry seasons. Again, the affected 

populations have relied almost exclusively on bitter 

cassava roots as the staple food (Tylleskär et al., 1991, 

1992). In konzo-affected villages, the urinary thiocyanate levels were 563–629 μmol/litre during the dry 

season and 344–381 μmol/litre during the wet season; in 

reference villages without konzo, the levels were on 

average 241 μmol/litre. However, the urinary concentrations of linamarin showed a closer association with 

the disease than those of thiocyanate, and the authors 

interpreted it to indicate that more important than 

cyanide in the causation of konzo might be the neurotoxic action of linamarin itself (Banea-Mayambu et al., 

1997). 

 Iodine deficiency and goitre, hypothyroidism, and 

cretinism are endemic in many areas of Africa. Several 

surveys in the endemic areas have demonstrated that 

there is also a strong correlation between cassava consumption and the thyroid effects (Delange & Ermans, 

1971; Delange et al., 1971; Ermans et al., 1972; JECFA, 

1993; Abuye et al., 1998). A cassava meal also diminished the uptake of 131I in the thyroid (Delange et al., 

1971). A study in rural Mozambique found that in a 

population suffering from endemic spastic paraparesis, 

adequate iodine intake mitigated against the development of hypothyroidism or goitre, and high levels of 

dietary cyanogenic glycosides fom cassava could be 

tolerated (Cliff et al., 1986). 

 Originally based on a geographical link between the 

prevalence of diabetes and cassava consumption 

(McGlashan, 1967), dietary exposure to cyanides has 

been linked to the malnutrition-related diabetes mellitus 

(WHO, 1985), also known as the “type-J” or “type-Z” 

diabetes (Hugh-Jones, 1955; Zuidema, 1959). The very 

existence of this third type of diabetes (in addition to the 

juvenile-onset and maturity-onset types) has been 

controversial (Gill, 1996), and not all studies have 

detected a relationship between cassava consumption 

and diabetes prevalence (Cooles, 1988; Swai et al., 

1992). The results of the standard glucose tolerance test 

were no more often abnormal among 88 Nigerian 

patients with tropical neuropathy than among 88 referents (Famuyiwa et al., 1995). 

8.2 Occupational exposure 

 Chronic occupational exposure to hydrogen cyanide 

per se resulting in serious injury is rather rare. 

 

1 Form of malnutrition caused by inadequate protein intake.

Symptoms of such poisonings include headache, 

dizziness, confusion, muscular weakness, poor vision, 

slurred speech, gastrointestinal tract disturbances, 

trauma, and enlarged thyroid. 

 A cross-sectional study was performed on the health 

effects of long-term cyanide exposure from a plating 

bath that contained 3% copper cyanide, 3% sodium 

cyanide, and 1% sodium chloride in the electroplating 

sections of three factories in Egypt that employed 

36 male workers (non-smokers) with 5–15 years of 

experience; cyanide concentrations in the breathing 

zones of workers (15-min averaging time) ranged from 

5 to 14 mg/m3

, the averages in the three factories being 

12, 7, and 9 mg/m3

 at the time of the study. There was 

also exposure to petrol fumes, solutions of strong soap 

and alkalis, and hydrochloric acid. The exposed group 

reported symptoms such as headache, weakness, changes 

in taste and smell, giddiness, irritation of the throat, 

vomiting, effort dyspnoea, lacrimation, salivation, and 

precordial pain more frequently than controls. Twenty of 

the exposed workers (56%) exhibited thyroid enlargement to a mild or moderate degree. None of the workers 

had clinical manifestations of hypo- or hyperthyroidism, 

but the exposed group showed a lower uptake of radiolabelled iodine in the thyroid; there was no difference in 

the protein-bound 131I. The exposed workers had significantly higher haemoglobin and cyanomethaemoglobin 

values and lymphocyte counts compared with 20 male 

unexposed controls. Punctate basophilia of erythrocytes 

was present in 28 of 36 subjects (El Ghawabi et al., 

1975). The contribution of the other exposures to the 

findings is difficult to discern. 

 A retrospective examination employing a questionnaire was performed with 36 former male workers 

(employees who could be reached and who volunteered, 

out of an unknown number of people actually employed) 

of a silver-reclaiming facility in the USA in 1983, which 

had been closed after the death of a worker because of 

cyanide poisoning. The only quantitative information on 

the concentrations of cyanide in the air came from a 24-h 

measurement 1 day after the factory had been closed; it 

was 17 mg/m3

. The study revealed a high prevalence of 

symptoms, including eye irritation, fatigue, dizziness, 

headache, disturbed sleep, ringing in ears, paraesthesia

of extremities, nausea, vomiting, dyspnoea, chest pain, 

palpitation, and weight loss (about 14% of workers 

reported palpitations, and 31% reported chest pain). 

Mild subclinical abnormalities in vitamin B12, folate, 

TSH levels, and thyroid function were found in silverreclaiming workers 7 months after cyanide exposure had 

ceased. It was noted that inhalation of hydrogen cyanide 

was not the only possible route of exposure of these 

workers in this occupational setting, as the questionnaire 

disclosed that more than half reported frequent direct 

contact with liquids containing cyanide and 22% of 

exposed workers were at risk of inadvertent cyanide 
Hydrogen cyanide and cyanides: Human health aspects 

29 

ingestion from food and drink in the production area 

(Blanc et al., 1985). 

 Effects of occupational exposure (5–19 years) of 

111 workers and 30 non-exposed referents to hydrogen 

cyanide were studied in two large case-hardening and 

electroplating facilities in India (Chandra et al., 1988). 

From a daily work profile and air cyanide measurements, the workers were categorized in exposure groups 

between 1.11 and 4.66 “cyanide-hours” (mg/m3

 × h). An 

abnormal psychological test result overall score (composite score of “delayed memory, visual ability, visual 

learning, and psychomotor ability”) was observed in 

31.5% of the exposed subjects, and an increase in the 

overall number of symptoms (headaches/heaviness in 

head, giddiness, lacrimation, itching of eyes, congestion 

of eyes, coated tongue) was found in 12.5% of the 

exposed workers. “Moderate” impairment in healthrelated scores showed an increase (no statistical analysis) at exposure levels in excess of 2.5 mg/m3

 × h in 

one factory and 4.35 mg/m3

 × h in the other, while 

findings classified as “diseased” were observed at levels 

in excess of 2.9 mg/m3

 × h. The authors did not provide 

the incidences of these findings among referents or 

actual measurements of cyanide concentrations in the 

air, and few details on the carrying out of the investigations were given.1

 Thiocyanate, the major detoxification product of 

cyanide, prevents the uptake of iodine and acts as a 

goitrogenic agent. This effect is more pronounced in 

individuals with decreased capacity to excrete thiocyanate in urine due to kidney dysfunction, etc. 

(VanderLaan & Bissell, 1946; Schultz, 1984; US EPA, 

1990; ATSDR, 1993). 

 Banerjee et al. (1997) reported a study of 35 male 

cyanide workers (of 201 male workers) who had worked 

in an Indian electroplating process of a cable industry for 

more than 5 consecutive years. Thirty-five non-exposed 

workers who had worked outside the manufacturing 

building were matched with the exposed workers for age 

and dietary habits. The mean serum thiocyanate concentration of the 35 non-smoking exposed employees was 

316 ± 15 μmol/litre, which was significantly higher (P < 

0.01) than that of the control subjects (90 ± 9.02 μmol/litre). Cyanide exposure resulted in a decrease of serum T4

and T3 concentrations (P < 0.05) and an increase in TSH 

concentration (P < 0.05) compared with the control subjects. 

 A case of cerebrovascular accident and hyperthyroidism with struma and another with struma and 

hypothyroidism were reported among metal case-

 

1 Apparently as a typographical error, all referents were also 

listed as “diseased.”

hardeners. No information on the level of exposure to 

cyanide was given (Hardy et al., 1950). 

 Leeser et al. (1990) reported a cross-sectional study, 

carried out between April and September 1986, of the 

health of sodium, copper, and potassium cyanide salt 

production workers from plants in a facility in the 

United Kingdom. Sixty-three employees from these 

cyanide salt plants were compared in a controlled study 

with 100 employees from a diphenyl oxide plant in the 

same facility. The breathing-zone cyanide concentrations 

ranged between 0.01 and 3.6 mg/m3

. Cyanide workers 

were examined before and after a block of six shifts in 

the spring and autumn, while diphenyl oxide workers 

were seen during their shifts. Haemoglobin and lymphocyte levels tended to be higher in the cyanide workers, 

although neither was pathologically raised, and no 

relationship between exposure and haematological 

findings was found. The absence of a dose–response 

relationship would suggest that cyanide work was not 

causal. Thyroid function was normal in both groups, and 

no goitres were found. Vitamin B12 and T4 levels 

revealed no differences between cyanide and diphenyl 

oxide exposure groups. 

 Biochemical effects of occupational and dietary 

exposure to cyanide were investigated in a preliminary 

study of cyanide poisoning from large-scale cassava 

processing and ingestion of cassava foods in Nigeria 

(Okafor et al., 2002). The study population included 

20 volunteers (female non-smokers, 24–50 years old and 

without overt signs of sickness or disease; 10 were 

cassava processors, 5 were “frequent” consumers of 

cassava, and 5 were “infrequent” consumers of cassava). 

The mean urinary thiocyanate level of the cassava 

processors (mean ± SD: 153.50 ± 25.2 μmol/litre) was 

2.2 and 2.6 times higher than that of frequent (mean ± 

SD: 70.1 ± 21.8 μmol/litre) and infrequent (mean ± SD: 

59.3 ± 17.0 μmol/litre) cassava consumers, respectively. 

An increase in plasma activity by 10% above normal 

ASAT (not statistically significant) was observed in 40% 

of the cassava processors, whereas it was within normal 

range in all consumers. No change was observed in the 

ALAT, alkaline phosphatase, or serum creatinine values. 

 There are no reported data on the carcinogenicity of 

cyanides in exposed human populations. 
Concise International Chemical Assessment Document 61 

30 

9. HEALTH EFFECTS EVALUATION 

9.1 Hazard identification and dose–

response assessment 

 The principal features of the toxicity profile for 

cyanide are its high acute toxicity with a very steep 

dose–effect curve and chronic toxicity, probably 

mediated through the main metabolite and detoxification 

product, thiocyanate. 

 Consistent with the results of studies in experimental animals, available data from case reports and the 

limited data from occupationally exposed populations 

and populations principally exposed to dietary cyanogenic glycosides from consumption of cassava indicate 

that the cardiovascular, respiratory, central nervous, and 

endocrine systems are the major targets of acute and 

chronic cyanide exposure by all routes. 

 The generally similar toxic effects of cyanide, 

whether acute or chronic, in animals and humans are 

believed to result primarily from inhibition of cellular 

respiration and consequent histotoxic anoxia. Effects on 

the thyroid resulting from long-term exposure are likely 

to be caused by thiocyanate.

 Human data on the concentration–effect relationship 

for acute cyanide toxicity are derived principally from 

case-studies of poisonings (accidental or intentional); as 

a result, characterization of concentration–response is 

uncertain. Whereas slight effects occur at inhalation 

exposure levels of 20–40 mg hydrogen cyanide/m3

, 50–

60 mg/m3

 can be tolerated without immediate or late 

effects for 20 min to 1 h, 120–150 mg/m3

 may lead to 

death after 0.5–1 h, 150 mg/m3

 is likely to be fatal 

within 30 min, 200 mg/m3

 is likely to be fatal after 

10 min, and 300 mg/m3

 is immediately fatal (DECOS, 

2002). Based on analyses of cyanide contents in tissues 

and in gastrointestinal tract contents from fatal poisoning 

cases (and comparative kinetics with dogs), Gettler & 

Baine (1938) estimated that death occurred after absorption of an average of 1.4 mg hydrogen cyanide/kg body 

weight; the lowest fatal absorbed dose was 0.54 mg 

hydrogen cyanide/kg body weight. Fatal intoxications 

have been reported after ingestion of apricot pits containing cyanogenic glycosides, especially in children. 

 Intravenous administration of nitroprusside, which 

liberates cyanide, has been reported to affect thyroid 

function in patients (Bödigheimer et al., 1979). In some 

(but not all) studies, thyroid dysfunction and goitre have 

been reported among cyanide-exposed workers (El 

Ghawabi et al., 1975; Blanc et al., 1985; Leeser et al., 

1990; Banerjee et al., 1997). Thyroid dysfunction in 

some of these individuals was reported to be accompanied by neurological symptoms, including headache, 

dizziness, and confusion, as well as mild subclinical 

abnormalities in vitamin B12 and folate (El Ghawabi et 

al., 1975; Blanc et al., 1985). Although this neurological 

and thyroid gland damage could not be unequivocally 

ascribed to cyanide, since other exposures may have 

occurred, the similarity of these lesions in humans to 

those produced in experimental animals treated with 

cyanide makes a strong case for the role of cyanide in 

these conditions. Limited information on exposure and 

confounding factors precludes the use of studies on 

people exposed at work in hazard characterization. 

 Long-term consumption of cassava containing high 

levels of cyanogenic glycosides, usually when constituting the principal source of calories, and associated 

with malnutrition and protein and vitamin deficiencies, 

has been associated with neurological diseases involving 

tropical ataxic neuropathy and endemic spastic paraparesis. In areas with low iodine intake, development of 

hypothyroidism and goitre, sometimes accompanied by

the neurological diseases, has also been linked to cassava. While daily cyanide exposure has been crudely 

estimated to be 15–50 mg/day in endemic areas, owing 

to the limitations of data on exposure, which is likely to 

be quite variable, and the potential impact of confounders, such as general malnutrition, low protein content of 

the diet, and iodine status, the available data do not 

provide meaningful information on dose–response for 

cyanide. 

 By extrapolating from time to death at different 

concentrations in single inhalation exposures, maximal 

non-lethal concentrations for dogs, rats, mice, rabbits, 

monkeys, cats, goats, and guinea-pigs were estimated to 

be 100–180 mg hydrogen cyanide/m3

 (Barcroft, 1931). 

 Cyanide is slightly irritating to the skin and eye 

(IPCS, 1992); data on the sensitizing properties of 

hydrogen cyanide and its alkali salts have not been 

identified. 

 Few repeated-dose toxicity studies have been 

performed (mainly because of the high acute toxicity), 

and the information on medium- to long-term effects is 

limited both for expected target organs and in the range 

of end-points studied. The possibility of mechanisms of 

chronic toxicity different from those of acute toxicity 

cannot, therefore, be totally excluded. 

 In a 13-week repeated-dose toxicity study (NTP, 

1993) in which cyanide was administered in drinkingwater, there were no clinical signs (associated with 

central nervous system effects) or histopathological 

effects in the brain or thyroid of rats and mice exposed 

to doses up to 12.5 and 26 mg/kg body weight per day, 

respectively. In contrast, effects on testicular and 

epididymal weight and testicular sperm counts and 
Hydrogen cyanide and cyanides: Human health aspects 

31 

epididymal sperm motility were observed in male rats at 

the highest dose level studied, 12.5 mg/kg body weight.

 In a 14-week repeated-dose toxicity study and in 

fertility toxicity studies in male and female rats, inhalation exposure to ACH (which is rapidly hydrolysed to 

hydrogen cyanide at physiological pH) resulted in no 

systemic toxicity at average ACH concentrations of 202, 

204, or 207 mg/m3

 (corresponding to 64, 65, and 66 mg 

hydrogen cyanide/m3

). In a similar 4-week inhalation 

study at an average ACH concentration of 211 mg/m3

(67 mg hydrogen cyanide/m3

), no systemic effects were 

observed, except on the first day of exposure, when the 

concentrations in the chamber fluctuated and reached 

values of 225 mg ACH/m3

 (71 mg hydrogen cyanide/m3

): 3 out of 10 animals died (Monsanto Co., 

1984a, 1985c). 

 Although somewhat limited, the weight of evidence 

of available data indicates that cyanide is not genotoxic 

and that it induces developmental effects only at doses 

or concentrations that are overtly toxic to the mothers. 

No data on cyanide carcinogenicity have been identified. 

9.2 Criteria for setting tolerable intakes/ 

concentrations for cyanides 

 The high acute toxicity of cyanide complicates the 

interpretation of available data as a basis for development of tolerable daily intakes or concentrations for 

potential effects associated with long-term low-level 

exposure to cyanide. 

 Available data in human populations are considered 

inadequate as a basis for characterization of dose–

response for long-term ingestion of cyanide because of 

very uncertain information on level and duration of 

exposure, likely confounding by simultaneous other 

exposures and dietary deficiencies, limited end-points 

studied, limited statistical power, and limited reporting. 

 Rather, effect levels in the animal studies considered most robust in the characterization of longer-term 

effects associated with cyanide are presented here as a 

basis for comparison with specific exposure levels (i.e., 

to facilitate development of margins of exposure for 

assessment of risk in specific, local, or regional circumstances). 

 In a 13-week repeated-dose toxicity study (NTP, 

1993) in which sodium cyanide was administered in 

drinking-water, there were no mortalities or clinical 

signs (associated with central nervous system effects) or 

histopathological effects in the brain, thyroid, or other 

organs of rats or mice exposed to doses up to 12.5 and 

26 mg/kg body weight per day, respectively. The reproductive tract in the males was the most sensitive organ to 

cyanide exposure in this study: lowered weight of testis 

and epididymis, together with a decrease in the number 

of spermatid heads in the testis and decreased motility of 

epididymal sperm, were observed at the highest dose 

level. The NOAEL in this study, 4.5 mg/kg body weight 

per day,1 is consistent with the only available long-term 

study, in that no adverse effects were observed in rats 

after 2 years of exposure to cyanide in the diet at 

10.8 mg cyanide/kg body weight per day (Howard & 

Hanzal, 1955). It is also roughly consistent with the 

NOAEL in the 14-week inhalation study (Monsanto Co., 

1984a) in which the airborne systemic no-effect level of 

204 mg ACH/m3

 can be estimated to correspond to a 

daily dose of approximately 15 mg cyanide/kg body 

weight per day. 

 The examination of neurotoxicity in the NTP (1993) 

study was limited to clinical observation and optical 

microscopy at autopsy. The few available studies 

specifically intended to investigate neurotoxicity suffer 

from major weaknesses: the study in miniature pigs 

(Jackson, 1988), which reported slight functional thyroid 

changes and behavioural aberrations at 1.2 mg cyanide/kg body weight per day, used a bolus dose with 

consequent high peaks of cyanide concentration in the 

organism and involved a very small number of animals 

(three animals in four groups) and limited statistical 

analysis. Similarly, the neuropathological study in goats 

(Soto-Blanco et al., 2002a), which reported ultrastructural changes in animals given ≥0.48 mg cyanide/kg 

body weight per day in drinking-water for 5 months, did 

not present quantitative data or statistical analysis. 

 Inhalation exposure is relevant principally to the 

occupational environment and in the vicinity of cassava 

processing facilities. For the reasons stated above, data 

on people exposed at work cannot be used to characterize the hazard for inhalation exposure. Information on 

repeated-exposure studies in animals exposed to hydrogen cyanide itself is scanty. In contrast, several studies 

are available on ACH, which is rapidly hydrolysed at 

physiological pH (Monsanto Co., 1984a, 1985c). Three 

separate studies give a systemic no-effect level of 202–

207 mg ACH/m3

, corresponding to 64–66 mg hydrogen 

cyanide/m3

. However, at an only slightly higher concentration of 225 mg ACH/m3

 (71 mg hydrogen cyanide/m3

), there was 30% mortality in one of the studies. 

The dose–effect relationship for cyanide is thus very 

steep for inhalation exposure. Because in these studies 

the effects observed were due to acute toxicity exclusively, they do not provide an adequate basis for the 

derivation of a tolerable concentration for any exposure 

of longer duration. 

 

1 ATSDR has used this information to derive an intermediateterm (15–364 days) exposure minimal risk level of 50 μg/kg 

body weight per day, applying uncertainty factors of 10 for 

interspecies extrapolation and 10 for human variability.
Concise International Chemical Assessment Document 61 

32 

9.3 Sample risk characterization 

 Information on levels of cyanide in air and water is 

limited and tends to be old. Adverse effects are not 

expected at the low levels reported in ambient air 

(usually below 1 μg/m3

). In the USA, concentrations in 

surface water and drinking-water are generally below 

10 μg/litre; at even the highest concentrations reported 

(200 μg/litre), adverse effects are not anticipated. 

 In the vicinity of cassava processing facilities, concentrations considerably in excess of those associated 

with adverse effects have been reported in both surface 

water and ambient air. Inadequately prepared cassava, 

when constituting the major part of the diet, may be 

hazardous. Concentrations of cyanogens in some other 

staple food items have been reported to be even higher 

than those in inadequately prepared cassava and are, 

therefore, potentially dangerous, although adverse health 

effects have not been reported. 

 Apricot and choke cherry kernels contain enough 

cyanogens to cause acute intoxication, and fatalities have 

been reported, especially in children. 

9.4 Uncertainties in the hazard 

characterization 

 Studies on humans deal mainly with acute effects of 

hydrogen cyanide/cyanides or, where longer term, lack 

adequate information on exposure and thus cannot be 

used in quantitative hazard characterization. Similarities 

in the likely mode of action and outcome from humans 

and experimental studies on animals, however, tend to 

confirm the most important end-points of hydrogen 

cyanide toxicity. 

 The available database on repeated-dose or chronic 

toxicity of cyanide is limited, primarily due to the high 

acute toxicity of the compound. While data are lacking 

on several relevant end-points such as carcinogenicity, 

significant longer-term adverse effects have not been 

induced at doses that have not been acutely toxic. 

 The contribution of factors other than cyanide in 

cassava-induced health impairment cannot be fully 

assessed. 

10. PREVIOUS EVALUATIONS BY 

INTERNATIONAL BODIES 

The WHO Guidelines for Drinking-water Quality 

(WHO, 2003) derived a tolerable daily intake of 

12 μg/kg body weight by considering 1.2 mg/kg body 

weight in the Jackson (1988) study as a LOAEL and 

applying an uncertainty factor of 100. By allocation of 

20% of the tolerable daily intake to drinking-water, a 

guideline value of 0.07 mg/litre was reached. 

 JECFA (1993) concluded that because of lack of 

quantitative toxicological and epidemiological information, a safe level of intake of cyanogenic glycosides 

could not be estimated. However, the committee concluded that a level of up to 10 mg hydrogen cyanide/kg 

in the Codex Standard for cassava flour is not associated 

with acute toxicity (JECFA, 1993). 
Hydrogen cyanide and cyanides: Human health aspects 

33 

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APPENDIX 1 — SOURCE DOCUMENTS 

ATSDR (1997) Toxicological profile for cyanide. 

Atlanta, GA, US Department of Health and 

Human Services, Public Health Service, Agency 

for Toxic Substances and Disease Registry 

The ATSDR Toxicological profile for cyanide may be 

ordered from: 

National Technical Information Service 

5285 Port Royal Road 

Springfield, VA 22161 

USA 

Telephone: (800) 553-6847 or (703) 605-6000 

It is also available online at 

http://www.atsdr.cdc.gov/toxprofiles/tp8.html. 

Chemical managers/authors of the ATSDR Toxicological 

profile on cyanide were: 

Carolyn Harper, Division of Toxicology, ATSDR, Atlanta, 

GA, USA 

Susan Goldhaber, Research Triangle Institute, Research 

Triangle Park, NC, USA 

The profile has undergone the following ATSDR internal 

reviews: 

1. Green Border Review: Green Border Review assures 

consistency with ATSDR policy. 

2. Health Effects Review: The Health Effects Review 

Committee examines the health effects chapter of 

each profile for consistency and accuracy in 

interpreting health effects and classifying end-points. 

3. Minimal Risk Level Review: The Minimal Risk Level 

Workgroup considers issues relevant to substancespecific minimal risk levels (MRLs), reviews the health 

effects database of each profile, and makes 

recommendations for derivation of MRLs. 

The peer review panel for cyanide consisted of the 

following members: 

Dr Joseph Borowitz, Professor of Pathology, Department of 

Pharmacology and Toxicology, School of Pharmacy and 

Pharmaceutical Sciences, Purdue University, West 

Lafayette, IN, USA 

Dr Gary Isom, Professor of Toxicology, Department of 

Pharmacology and Toxicology, Purdue University, West 

Lafayette, IN, USA 

Dr James Way, Professor of Pharmacology and 

Toxicology, Department of Medical Pharmacology and 

Toxicology, Texas A&M University, College Station, TX, 

USA 

JECFA (1993) Cyanogenic glycosides. In: 

Toxicological evaluation of certain food 

additives and naturally occurring toxicants. 

Geneva, World Health Organization, 39th 

Meeting of the Joint FAO/WHO Expert 

Committee on Food Additives (WHO Food 

Additives Series 30)

 The JECFA monograph Cyanogenic glycosides is available 

from: 

 Marketing and Dissemination 

World Health Organization 

1211 Geneva 27 

Switzerland 

or at bookorders@who.int. It is also available online at 

http://www.inchem.org/documents/jecfa/jecmono/v30je18.htm. 

 The first draft of the document was prepared by Dr G. 

Speijers, Laboratory for Toxicology, National Institute of Public 

Health and Environmental Protection, Bilthoven, The 

Netherlands. The document was reviewed at the 39th meeting 

of the Joint FAO/WHO Expert Committee on Food Additives 

(JECFA). 

 The procedure for the preparation of the JECFA 

monographs is described at 

http://www.who.int/pcs/jecfa/FA%20procedural%20guidelines.pd

f.
Concise International Chemical Assessment Document 61 

42 

APPENDIX 2 — CICAD PEER REVIEW 

 The two consecutive drafts of the CICAD on hydrogen 

cyanide and cyanides (human health aspects) were sent for 

review to IPCS national Contact Points and Participating 

Institutions, as well as to identified experts. Comments were 

received from: 

M. Baril, Institut de Recherche en Santé et en Sécurité du 

Travail, Montreal, Canada 

R. Benson, Drinking Water Program, US Environmental 

Protection Agency, Denver, CO, USA 

D. Chakrabarti, Jadavpur University, Calcutta, India 

R.S. Chhabra, National Institute of Environmental Health 

Sciences, Research Triangle Park, NC, USA 

N. Chiu, Office of Water, US Environmental Protection 

Agency, Washington, DC, USA 

M. Cikrt, National Institute of Public Health, Prague, Czech 

Republic 

C. Cooke, Health and Safety Executive, Bootle, 

Merseyside, United Kingdom 

I. Desi, University of Szeged, Szeged, Hungary 

G. Dura, National Institute of Environmental Health of 

Jozsef Fodor, Budapest, Hungary 

C. Elliot-Minty, Health and Safety Executive, Bootle, 

Merseyside, United Kingdom 

H. Greim, National Research Center for Environment and 

Health, Technical University of Munich, Munich, Germany 

M. Gully, Health Canada, Ottawa, Canada 

G.K. Hatfield, National Institute for Occupational Safety and 

Health, Cincinnati, OH, USA 

R.F. Hertel, Federal Institute for Risk Assessment, Berlin, 

Germany 

J. Hopkins, Toxicology Advice & Consulting Ltd, Sutton, 

Surrey, United Kingdom 

P. Howe, Centre for Ecology and Hydrology, Monks Wood, 

United Kingdom 

S. Jacobi, Cyanides Task Force, European Centre for 

Ecotoxicology and Toxicology of Chemicals (ECETOC), 

and European Chemical Industry Council (CEFIC), 

Brussels, Belgium 

U. Kierdorf, Justus-Liebig-University of Giessen, Giessen, 

Germany 

G. Koennecker, Fraunhofer Institute for Toxicology and 

Experimental Medicine, Hanover, Germany 

T. Kuiper-Goodman, Health Canada, Ottawa, Canada 

S. Melching-Kollmuβ, Fraunhofer Institute for Toxicology 

and Experimental Medicine, Hanover, Germany 

L. Murthy, National Institute for Occupational Safety and 

Health, Cincinnati, OH, USA 

M.A. Pemberton, Cyanides Task Force, European Centre 

for Ecotoxicology and Toxicology of Chemicals (ECETOC), 

and European Chemical Industry Council (CEFIC), 

Brussels, Belgium 

J. Rantanen, Institute of Occupational Health, Helsinki, 

Finland 

T. Santonen, Institute of Occupational Health, Helsinki, 

Finland 

S. Schmidt, Fraunhofer Institute for Toxicology and 

Experimental Medicine, Hanover, Germany 

P. Schulte, National Institute for Occupational Safety and 

Health, Cincinnati, OH, USA 

J.C. Stadler, DuPont Haskell Laboratory, Newark, DE, USA 

J.L. Stauber, Commonwealth Scientific and Industrial 

Research Organisation (CSIRO) Energy Technology, 

Bangor, NSW, Australia 

U. Stenius, Karolinska Institute, Stockholm, Sweden 

J.H.M. Temmink, Wageningen Agricultural University, 

Wageningen, The Netherlands 

S. Vainiotalo, Institute of Occupational Health, Helsinki, 

Finland 

A. Vyskocil, University of Montreal, Montreal, Canada 

D. Willcocks, Existing Chemicals, National Industrial 

Chemicals Notification and Assessment Scheme 

(NICNAS), Sydney, NSW, Australia 

K. Ziegler-Skylakakis, Commission of European 

Communities, Luxembourg 
Hydrogen cyanide and cyanides: Human health aspects 

43 

APPENDIX 3 — 10TH FINAL REVIEW 

BOARD 

Monks Wood, United Kingdom 

16–19 September 2002

Members 

Dr R. Benson, US Environmental Protection Agency, Region 

VIII, Denver, CO, USA 

Mr R. Cary, Health and Safety Executive, Bootle, Merseyside, 

United Kingdom 

Dr R. Chhabra, National Institute of Environmental Health 

Sciences, Research Triangle Park, NC, USA 

Dr S. Chou, Agency for Toxic Substances and Disease Registry 

(ATSDR), Atlanta, GA, USA 

Dr S. Czerczak, Nofer Institute of Occupational Medicine, Lodz, 

Poland 

Dr S. Dobson, Centre for Ecology and Hydrology, Monks Wood, 

Abbots Ripton, Huntingdon, Cambridgeshire, United Kingdom 

Dr G. Dura, National Institute of Environmental Health, Jozsef 

Fodor Public Health Centre, Budapest, Hungary 

Dr L. Fishbein, Fairfax, VA, USA 

Dr H. Gibb, National Center for Environmental Assessment, US 

Environmental Protection Agency, Washington, DC, USA 

Dr Y. Hayashi, Division of Chem-Bio Informatics, National 

Institute of Health Sciences, Ministry of Health, Labour and 

Welfare, Tokyo, Japan 

Dr R.F. Hertel, Federal Institute for Health Protection of 

Consumers and Veterinary Medicine, Berlin, Germany 

Dr A. Hirose, Division of Risk Assessment, National Institute of 

Health Sciences, Tokyo, Japan 

Mr P. Howe, Centre for Ecology and Hydrology, Monks Wood, 

Abbots Ripton, Huntingdon, Cambridgeshire, United Kingdom 

Prof. J. Jeyaratnam, Colombo, Sri Lanka 

Dr J. Kielhorn, Fraunhofer Institute of Toxicology and Aerosol 

Research, Hanover, Germany 

Prof. Y.-X. Liang, School of Public Health, Fudan University, 

Shanghai Medical College, Shanghai, People’s Republic of 

China 

Dr R. Liteplo, Existing Substances Division, Environmental 

Contaminants Bureau, Health Canada, Ottawa, Ontario, Canada 

Ms M.E. Meek, Existing Substances Division, Safe 

Environments Programme, Health Canada, Ottawa, Ontario, 

Canada 

Mr F.K. Muchiri, Directorate of Occupational Health and Safety 

Services, Nairobi, Kenya 

Dr O. Sabzevari, Department of Toxicology & Pharmacology, 

Faculty of Pharmacy, Tehran University of Medical Sciences, 

Tehran, Iran 

Dr J. Sekizawa, Division of Chem-Bio Informatics, National 

Institute of Health Sciences, Tokyo, Japan 

Dr F.P. Simeonova, Sofia, Bulgaria 

Dr J. Stauber, CSIRO Energy Technology, Centre for Advanced 

Analytical Chemistry, Bangor, Australia 

Dr M.H. Sweeney, Document Development Branch, Education 

and Information Division, National Institute for Occupational 

Safety and Health, Cincinnati, OH, USA 

Dr K. Ziegler-Skylakakis, European Commission, DG 

Employment & Social Affairs, Luxembourg 

Resource Persons

Dr C. Cowles, Health and Safety Executive, Industrial Chemicals 

Unit HD, Bootle, Merseyside, United Kingdom 

Dr C. Elliott-Minty, Health and Safety Executive, Industrial 

Chemicals Unit HD, Bootle, Merseyside, United Kingdom 

Dr K. Fuller, Health and Safety Executive, Industrial Chemicals 

Unit HD, Bootle, Merseyside, United Kingdom 

 

Observers

Mr A.G. Berends, Solvay S.A., Brussels, Belgium; European 

Chemical Industry Council / European Centre for Ecotoxicology 

and Toxicology of Chemicals (CEFIC/ECETOC) 

Mr W. Gulledge, American Chemistry Council, Arlington, VA, 

USA 

Mr C. Newsome, Dow Chemical Company Limited, West 

Drayton, Middlesex, United Kingdom; European Chemical 

Industry Council / European Centre for Ecotoxicology and 

Toxicology of Chemicals (CEFIC/ECETOC) 

Mr M.A. Pemberton, Wilmslow, United Kingdom; European 

Chemical Industry Council / European Centre for Ecotoxicology 

and Toxicology of Chemicals (CEFIC/ECETOC) 

Mr W. Stott, Dow Chemical Company, Midland, MI, USA; 

European Chemical Industry Council / European Centre for 

Ecotoxicology and Toxicology of Chemicals (CEFIC/ECETOC) 

Mr J.M. Waechter, Jr, The Dow Chemical Company, Midland, 

MI, USA; European Chemical Industry Council / European 

Centre for Ecotoxicology and Toxicology of Chemicals 

(CEFIC/ECETOC) 

Secretariat

Dr A. Aitio, International Programme on Chemical Safety, World 

Health Organization, Geneva, Switzerland 

Mr T. Ehara, International Programme on Chemical Safety, 

World Health Organization, Geneva, Switzerland 

Mr H. Malcolm, Centre for Ecology and Hydrology, Monks 

Wood, Abbots Ripton, Huntingdon, Cambridgeshire, United 

Kingdom 

Ms C. Vickers, International Programme on Chemical Safety, 

World Health Organization, Geneva, Switzerland
Concise International Chemical Assessment Document 61 

44 

APPENDIX 4 — 11TH FINAL REVIEW 

BOARD 

Varna, Bulgaria 

8–11 September 2003

Members 

Dr I. Benchev, Sofia, Bulgaria 

Dr R. Chhabra, National Institute of Environmental Health 

Sciences, Research Triangle Park, NC, USA 

Dr C. De Rosa, Agency for Toxic Substances and Disease 

Registry, Centers for Disease Control and Prevention, Atlanta, 

GA, USA 

Dr S. Dobson, Centre for Ecology and Hydrology, Monks Wood, 

Abbots Ripton, Huntingdon, Cambridgeshire, United Kingdom 

Dr G. Dura, National Institute of Environment, József Fodor 

Public Health Centre, Budapest, Hungary 

Dr L. Fishbein, Fairfax, VA, USA 

Dr H. Gibb, National Center for Environmental Assessment, US 

Environmental Protection Agency, Washington, DC, USA 

Dr R.F. Hertel, Federal Institute for Risk Assessment, Berlin, 

Germany 

Mr P. Howe, Centre for Ecology and Hydrology, Monks Wood, 

Abbots Ripton, Huntingdon, Cambridgeshire, United Kingdom 

Dr S. Ishimitsu, Division of Safety Information on Drug, Food 

and Chemicals, National Institute of Hygienic Sciences, Tokyo, 

Japan 

Dr D. Kanungo, Central Insecticides Board, Directorate of Plant 

Protection, Quarantine & Storage, Ministry of Agriculture, 

Haryana, India 

Dr J. Kielhorn, Fraunhofer Institute for Toxicology and 

Experimental Medicine, Hanover, Germany 

Ms B. Meek, Environmental Health Directorate, Health Canada, 

Ottawa, Ontario, Canada 

Dr T. Morita, Division of Safety Information on Drug, Food and 

Chemicals, National Institute of Hygienic Sciences, Tokyo, 

Japan 

Mr F.K. Muchiri, Directorate of Occupational Health and Safety 

Services, Nairobi, Kenya 

Dr L. Olsen, Biological Monitoring & Health Assessment Branch, 

Division of Applied Research & Technology, National Institute 

for Occupational Safety and Health, Cincinnati, OH, USA 

Dr N. Rizov, National Center of Hygiene, Medical Ecology and 

Nutrition, Sofia, Bulgaria 

Dr P. Schulte, Education and Information Division, National 

Institute for Occupational Safety and Health, Cincinnati, OH, 

USA 

Dr J. Sekizawa, Faculty of Integrated Arts and Sciences, 

Tokushima University, Tokushima, Japan 

Dr F.P. Simeonova, Sofia, Bulgaria 

Dr S. Soliman, Faculty of Agriculture, Alexandria University, El 

Shatby, Alexandria, Egypt 

Dr J. Stauber, CSIRO Energy Technology, Centre for Advanced 

Analytical Chemistry, Bangor, NSW, Australia 

Mr P. Watts, Toxicology Advice & Consulting Ltd, Surrey, United 

Kingdom 

Ms D. Willcocks, National Industrial Chemicals Notification and 

Assessment Scheme, Sydney, NSW, Australia 

Dr K. Ziegler-Skylakakis, European Commission, Luxembourg 

 

Observers 

Dr S. Jacobi, Degussa AG, Fine Chemicals, Hanau-Wolfgang, 

Germany 

Mr M. Southern, Shell International Petroleum Company Ltd, 

London, United Kingdom 

Dr W. ten Berge, DSM, Heerlen, The Netherlands 

Secretariat

Dr A. Aitio, International Programme on Chemical Safety, World 

Health Organization, Geneva, Switzerland 

Mr T. Ehara, International Programme on Chemical Safety, 

World Health Organization, Geneva, Switzerland 
Hydrogen cyanide and cyanides: Human health aspects 

45 

APPENDIX 5 — ABBREVIATIONS AND 

ACRONYMS 

ACH acetone cyanohydrin 

ALAT alanine aminotransferase 

ASAT aspartate aminotransferase 

ATSDR Agency for Toxic Substances and Disease Registry 

(USA) 

CAS Chemical Abstracts Service 

CHO Chinese hamster ovary 

CICAD Concise International Chemical Assessment 

Document 

DNA deoxyribonucleic acid 

EHC Environmental Health Criteria 

EPA Environmental Protection Agency (USA) 

FAO Food and Agriculture Organization of the United 

 Nations 

HGPRT hypoxanthine–guanine phosphoribosyltransferase 

ILO International Labour Organization 

IPCS International Programme on Chemical Safety 

JECFA Joint FAO/WHO Expert Committee on Food Additives 

Kow octanol/water partition coefficient 

LC50 median lethal concentration 

LD50 median lethal dose 

LOAEL lowest-observed-adverse-effect level 

MAK Maximum Allowable Concentration (Germany) 

MRL minimal risk level 

NIOSH National Institute for Occupational Safety and Health 

(USA) 

NOAEL no-observed-adverse-effect level 

NOEL no-observed-effect level 

PIM Poison Information Monograph 

SD standard deviation 

SI International System of Units (Système international 

d’unités) 

T3 triiodothyronine 

T4 thyroxine 

TSH thyroid-stimulating hormone 

UNEP United Nations Environment Programme 

USA United States of America 

US EPA United States Environmental Protection Agency 

WHO World Health Organization 
Prepared in the context of cooperation between the International

Programme on Chemical Safety and the European Commission 

© IPCS 2002

SEE IMPORTANT INFORMATION ON THE BACK.

IPCS

International

Programme on

Chemical Safety

HYDROGEN CYANIDE, LIQUEFIED 0492

May 2003

CAS No: 74-90-8

RTECS No: MW6825000

UN No: 1051

EC No: 006-006-00-X

Hydrocyanic acid

Prussic acid

Formonitrile

HCN

Molecular mass: 27.03

TYPES OF

HAZARD/

EXPOSURE

ACUTE HAZARDS/SYMPTOMS PREVENTION FIRST AID/FIRE FIGHTING

FIRE Extremely flammable. Gives off

irritating or toxic fumes (or gases)

in a fire.

NO open flames, NO sparks, and

NO smoking.

Shut off supply; if not possible and

no risk to surroundings, let the fire

burn itself out; in other cases

extinguish with powder, water spray,

foam, carbon dioxide.

EXPLOSION Gas/air mixtures are explosive. Closed system, ventilation,

explosion-proof electrical equipment

and lighting.

In case of fire: keep cylinder cool by

spraying with water. Combat fire

from a sheltered position.

EXPOSURE AVOID ALL CONTACT! IN ALL CASES CONSULT A

DOCTOR!

Inhalation Confusion. Drowsiness.

Headache. Nausea. Convulsions.

Shortness of breath.

Unconsciousness. Death.

Ventilation, local exhaust, or

breathing protection.

Fresh air, rest. Half-upright position.

No mouth-to-mouth artificial

respiration. Administer oxygen by

trained personnel. Refer for medical

attention. See Notes.

Skin MAY BE ABSORBED! (Further see

Inhalation).

Protective gloves. Protective

clothing.

Rinse skin with plenty of water or

shower. Refer for medical attention.

Wear protective gloves when

administering first aid.

Eyes VAPOUR WILL BE ABSORBED!

Redness. (See Inhalation).

Safety goggles, or eye protection in

combination with breathing

protection.

First rinse with plenty of water for

several minutes (remove contact

lenses if easily possible), then take

to a doctor.

Ingestion Burning sensation. (Further see

Inhalation).

Do not eat, drink, or smoke during

work. Wash hands before eating.

Rinse mouth. Do NOT induce

vomiting. No mouth-to-mouth

artificial respiration. Administer

oxygen by trained personnel. Refer

for medical attention. See Notes.

SPILLAGE DISPOSAL PACKAGING & LABELLING

Evacuate danger area immediately! Consult an

expert! Ventilation. Remove all ignition sources.

Absorb remaining liquid in sand or inert absorbent

and remove to safe place. NEVER direct water jet

on liquid. Do NOT let this chemical enter the

environment. Gas-tight chemical protection suit

including self-contained breathing apparatus.

F+ Symbol

T+ Symbol

N Symbol

R: 12-26-50/53

S: (1/2-)7/9-16-36/37-38-45-60-61

UN Hazard Class: 6.1

UN Subsidiary Risks: 3

UN Pack Group: I

Marine pollutant.

EMERGENCY RESPONSE STORAGE

Transport Emergency Card: TEC (R)-61S1051

NFPA Code: H4; F4; R2

Fireproof. Separated from food and feedstuffs. Cool. Store only if stabilized.
Boiling point: 26°C

Melting point: -13°C

Relative density (water = 1): 0.69 (liquid)

Solubility in water: miscible

Vapour pressure, kPa at 20°C: 82.6

Relative vapour density (air = 1): 0.94

Flash point: -18°C c.c.

Auto-ignition temperature: 538°C

Explosive limits, vol% in air: 5.6-40.0

Octanol/water partition coefficient as log Pow: -0.25

LEGAL NOTICE Neither the EC nor the IPCS nor any person acting on behalf of the EC or the IPCS is responsible

 for the use which might be made of this information

©IPCS 2002

0492 HYDROGEN CYANIDE, LIQUEFIED

IMPORTANT DATA

Physical State; Appearance

COLOURLESS GAS OR LIQUID, WITH CHARACTERISTIC

ODOUR.

Physical dangers

The gas mixes well with air, explosive mixtures are easily

formed.

Chemical dangers

The substance may polymerize due to heating under the

influence of base(s), over 2% water, or if not chemically

stabilized, with fire or explosion hazard. On combustion, forms

toxic and corrosive gases including nitrogen oxides. The

solution in water is a weak acid. Reacts violently with oxidants,

hydrogen chloride in alcoholic mixtures, causing fire and

explosion hazard.

Occupational exposure limits

TLV: 4.7 ppm; (Ceiling value); (skin); (ACGIH 2003).

MAK: 1.9 ppm, 2.1 mg/m3

; H; Peak limitation category: II(2);

Pregnancy risk group: C; (DFG 2002).

Routes of exposure

The substance can be absorbed into the body by inhalation,

through the skin and by ingestion.

Inhalation risk

A harmful contamination of the air will be reached very quickly

on evaporation of this substance at 20°C.

Effects of short-term exposure

The substance is irritating to the eyes and the respiratory tract.

The substance may cause effects on the cellular respiration,

resulting in convulsions and unconsciousness. Exposure may

result in death. Medical observation is indicated. See Notes.

Effects of long-term or repeated exposure

The substance may have effects on the thyroid.

PHYSICAL PROPERTIES

ENVIRONMENTAL DATA

The substance is very toxic to aquatic organisms.

NOTES

The occupational exposure limit value should not be exceeded during any part of the working exposure.

Specific treatment is necessary in case of poisoning with this substance; the appropriate means with instructions must be available.

The odour warning when the exposure limit value is exceeded is insufficient.

The recommendations on this Card also apply to hydrogen cyanide, stabilized, absorbed in a porous inert material.

Other UN numbers: 1613, Hydrogen cyanide, aqueous solution, not more than 20% of hydrogen cyanide; 1614, Hydrogen cyanide

stabilized, absorbed in a porous inert material; 3294, Hydrogen cyanide solution in alcohol, not more than 45% of hydrogen

cyanide.

Never work alone in an area if hydrogen cyanide exposure is possible.

Depending on the degree of exposure, periodic medical examination is suggested.

ADDITIONAL INFORMATION
Prepared in the context of cooperation between the International

Programme on Chemical Safety and the European Commission 

© IPCS 2002

SEE IMPORTANT INFORMATION ON THE BACK.

IPCS

International

Programme on

Chemical Safety

SODIUM CYANIDE 1118

May 2003

CAS No: 143-33-9

RTECS No: VZ7525000

UN No: 1689

EC No: 006-007-00-5

Hydrocyanic acid, sodium salt

NaCN

Molecular mass: 49.01

TYPES OF

HAZARD/

EXPOSURE

ACUTE HAZARDS/SYMPTOMS PREVENTION FIRST AID/FIRE FIGHTING

FIRE Not combustible but forms

flammable gas on contact with

water or damp air. Gives off

irritating or toxic fumes (or gases)

in a fire.

NO hydrous agents. NO water. NO

carbon dioxide. In case of fire in the

surroundings: foam and powder.

EXPLOSION In case of fire: cool drums, etc., by

spraying with water but avoid

contact of the substance with water.

EXPOSURE PREVENT DISPERSION OF DUST!

STRICT HYGIENE!

IN ALL CASES CONSULT A

DOCTOR!

Inhalation Sore throat. Headache. Confusion.

Weakness. Shortness of breath.

Convulsions. Unconsciousness.

Local exhaust or breathing

protection.

Fresh air, rest. No mouth-to-mouth

artificial respiration. Administer

oxygen by trained personnel. Refer

for medical attention.

Skin MAY BE ABSORBED! Redness.

Pain. (Further see Inhalation).

Protective gloves. Protective

clothing.

Remove contaminated clothes.

Rinse skin with plenty of water or

shower. Refer for medical attention.

Eyes Redness. Pain. (Further see

Inhalation).

Safety goggles, face shield, or eye

protection in combination with

breathing protection if powder.

First rinse with plenty of water for

several minutes (remove contact

lenses if easily possible), then take

to a doctor.

Ingestion Burning sensation. Nausea.

Vomiting. Diarrhoea. (See

Inhalation).

Do not eat, drink, or smoke during

work. Wash hands before eating.

Induce vomiting (ONLY IN

CONSCIOUS PERSONS!). Wear

protective gloves when inducing

vomiting. No mouth-to-mouth

artificial respiration. Administer

oxygen by trained personnel. Refer

for medical attention. See Notes.

SPILLAGE DISPOSAL PACKAGING & LABELLING

Evacuate danger area! Consult an expert!

Ventilation. Sweep spilled substance into dry,

sealable and labelled containers. Cautiously

neutralize remainder with sodium hypochlorite

solution. Then wash away with plenty of water. Do

NOT let this chemical enter the environment.

Chemical protection suit including self-contained

breathing apparatus.

T+ Symbol

N Symbol

R: 26/27/28-32-50/53

S: (1/2-)7-28-29-45-60-61

Note: A

UN Hazard Class: 6.1

UN Pack Group: I

Airtight. Unbreakable packaging;

put breakable packaging into closed

unbreakable container. Do not

transport with food and feedstuffs.

Marine pollutant.

EMERGENCY RESPONSE STORAGE

Transport Emergency Card: TEC (R)-61S1689

NFPA Code: H3; F0; R0

Separated from strong oxidants, acids, food and feedstuffs, carbon dioxide,

water or products containing water. Dry. Well closed. Keep in a

well-ventilated room.
Boiling point: 1496°C

Melting point: 563.7°C

Density: 1.6 g/cm3

Solubility in water, g/100 ml at 20°C: 58

LEGAL NOTICE Neither the EC nor the IPCS nor any person acting on behalf of the EC or the IPCS is responsible

 for the use which might be made of this information

©IPCS 2002

1118 SODIUM CYANIDE

IMPORTANT DATA

Physical State; Appearance

WHITE, HYGROSCOPIC CRYSTALLINE POWDER, WITH

CHARACTERISTIC ODOUR. ODOURLESS WHEN DRY.

Chemical dangers

The substance decomposes rapidly on contact with acids, and

slowly on contact with water, moisture or carbon dioxide

producing hydrogen cyanide (see ICSC 0492). The solution in

water is a medium strong base.

Occupational exposure limits

TLV: as CN 5 mg/m3

; (Ceiling value); (skin); (ACGIH 2003).

MAK: 3.8 mg/m3

 I; H; Peak limitation category: II(1); Pregnancy

risk group: C; (DFG 2002).

Routes of exposure

The substance can be absorbed into the body by inhalation,

through the skin and by ingestion.

Inhalation risk

A harmful concentration of airborne particles can be reached

quickly when dispersed.

Effects of short-term exposure

The substance is severely irritating to the eyes, the skin and the

respiratory tract. The substance may cause effects on the

cellular respiration, resulting in convulsions and

unconsciousness. Exposure may result in death. Medical

observation is indicated. See Notes.

Effects of long-term or repeated exposure

The substance may have effects on the thyroid.

PHYSICAL PROPERTIES

ENVIRONMENTAL DATA

The substance is very toxic to aquatic organisms.

NOTES

The occupational exposure limit value should not be exceeded during any part of the working exposure.

Specific treatment is necessary in case of poisoning with this substance; the appropriate means with instructions must be available.

Do NOT take working clothes home.

Depending on the degree of exposure, periodic medical examination is suggested.

Never work alone in an area if hydrocyanic acid exposure is possible.

ADDITIONAL INFORMATION
Prepared in the context of cooperation between the International

Programme on Chemical Safety and the European Commission 

© IPCS 2002

SEE IMPORTANT INFORMATION ON THE BACK.

IPCS

International

Programme on

Chemical Safety

POTASSIUM CYANIDE 0671

May 2003

CAS No: 151-50-8

RTECS No: TS8750000

UN No: 1680

EC No: 006-007-00-5

Hydrocyanic acid, potassium salt

KCN

Molecular mass: 65.1

TYPES OF

HAZARD/

EXPOSURE

ACUTE HAZARDS/SYMPTOMS PREVENTION FIRST AID/FIRE FIGHTING

FIRE Not combustible but forms

flammable gas on contact with

water or damp air. Gives off

irritating or toxic fumes (or gases)

in a fire.

NO hydrous agents. NO water. NO

carbon dioxide. In case of fire in the

surroundings: foam and powder.

EXPLOSION In case of fire: cool drums, etc., by

spraying with water but avoid

contact of the substance with water.

EXPOSURE PREVENT DISPERSION OF DUST!

STRICT HYGIENE!

IN ALL CASES CONSULT A

DOCTOR!

Inhalation Sore throat. Headache. Confusion.

Weakness. Shortness of breath.

Convulsions. Unconsciousness.

Local exhaust or breathing

protection.

Fresh air, rest. No mouth-to-mouth

artificial respiration. Administer

oxygen by trained personnel. Refer

for medical attention.

Skin MAY BE ABSORBED! Redness.

Pain. (Further see Inhalation).

Protective gloves. Protective

clothing.

Remove contaminated clothes.

Rinse skin with plenty of water or

shower. Refer for medical attention.

Eyes Redness. Pain. (Further see

Inhalation).

Safety goggles, face shield, or eye

protection in combination with

breathing protection.

First rinse with plenty of water for

several minutes (remove contact

lenses if easily possible), then take

to a doctor.

Ingestion Burning sensation. Nausea.

Vomiting. Diarrhoea. (See

Inhalation).

Do not eat, drink, or smoke during

work. Wash hands before eating.

Induce vomiting (ONLY IN

CONSCIOUS PERSONS!). Wear

protective gloves when inducing

vomiting. No mouth-to-mouth

artificial respiration. Administer

oxygen by trained personnel. Refer

for medical attention.

SPILLAGE DISPOSAL PACKAGING & LABELLING

Evacuate danger area! Consult an expert!

Ventilation. Sweep spilled substance into dry

sealable and labelled containers. Cautiously

neutralize remainder with sodium hypochlorite

solution. Then wash away with plenty of water. Do

NOT let this chemical enter the environment.

Chemical protection suit including self-contained

breathing apparatus.

T+ Symbol

N Symbol

R: 26/27/28-32-50/53

S: (1/2-)7-28-29-45-60-61

Note: A

UN Hazard Class: 6.1

UN Pack Group: I

Airtight. Unbreakable packaging;

put breakable packaging into closed

unbreakable container. Do not

transport with food and feedstuffs.

Marine pollutant.

EMERGENCY RESPONSE STORAGE

Transport Emergency Card: TEC (R)-61S1680.

NFPA Code: H3; F0; R0

Separated from strong oxidants, acids, food and feedstuffs, carbon dioxide,

water, or products containing water. Dry. Well closed. Keep in a

well-ventilated room.
Boiling point: 1625°C

Melting point: 634°C

Density: 1.52 g/cm3

Solubility in water, g/100 ml: 71.6

LEGAL NOTICE Neither the EC nor the IPCS nor any person acting on behalf of the EC or the IPCS is responsible

 for the use which might be made of this information

©IPCS 2002

0671 POTASSIUM CYANIDE

IMPORTANT DATA

Physical State; Appearance

HYGROSCOPIC CRYSTALS OR SOLID IN VARIOUS FORMS,

WITH CHARACTERISTIC ODOUR. ODOURLESS WHEN DRY.

Chemical dangers

The substance decomposes rapidly on contact with acids, and

slowly on contact with water, moisture or carbon dioxide

producing hydrogen cyanide (see ICSC 0492). The solution in

water is a medium strong base.

Occupational exposure limits

TLV: as CN 5 mg/m3

; (Ceiling value); (skin); (ACGIH 2003).

MAK: 5.0 mg/m3

 I; H; Pregnancy risk group: C; Peak limitation

category: II(1); (DFG 2002).

Routes of exposure

The substance can be absorbed into the body by inhalation,

through the skin and by ingestion.

Inhalation risk

A harmful concentration of airborne particles can be reached

quickly when dispersed.

Effects of short-term exposure

The substance is severely irritating to the eyes, the skin and the

respiratory tract. The substance may cause effects on the

cellular respiration, resulting in convulsions and

unconsciousness. Exposure may result in death. Medical

observation is indicated. See Notes.

Effects of long-term or repeated exposure

The substance may have effects on the thyroid.

PHYSICAL PROPERTIES

ENVIRONMENTAL DATA

This substance may be hazardous to the environment; special attention should be given to aquatic organisms.

NOTES

The occupational exposure limit value should not be exceeded during any part of the working exposure.

Specific treatment is necessary in case of poisoning with this substance; the appropriate means with instructions must be available.

Depending on the degree of exposure, periodic medical examination is suggested.

Do NOT take working clothes home.

Never work alone in an area if hydrogen cyanide exposure is possible.

ADDITIONAL INFORMATION
Prepared in the context of cooperation between the International

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© IPCS 1999

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Programme on

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CALCIUM CYANIDE 0407

November 1998

CAS No: 592-01-8

RTECS No: EW0700000

UN No: 1575

EC No: 020-002-00-5

Calcyanide

Calcyan

C2CaN2 / Ca(CN)2

Molecular mass: 92.1

TYPES OF

HAZARD/

EXPOSURE

ACUTE HAZARDS/SYMPTOMS PREVENTION FIRST AID/FIRE FIGHTING

FIRE Not combustible but forms

flammable gas on contact with

water or damp air. Gives off

irritating or toxic fumes (or gases)

in a fire.

NO open flames, NO sparks, and

NO smoking. NO contact with

water, carbon dioxide, acids. NO

contact with hot surfaces.

Powder, dry sand, NO hydrous

agents. NO water. NO carbon

dioxide.

EXPLOSION

EXPOSURE STRICT HYGIENE! IN ALL CASES CONSULT A

DOCTOR!

Inhalation Chest tightness. Confusion.

Convulsions. Cough. Dizziness.

Headache. Laboured breathing.

Nausea. Shortness of breath.

Unconsciousness. Vomiting.

Weakness. Red coloration of the

skin.

Local exhaust or breathing

protection.

Fresh air, rest. Artificial respiration

if indicated. Refer for medical

attention. See Notes.

Skin MAY BE ABSORBED! Redness.

Pain. (Further see Inhalation).

Protective gloves. Protective

clothing.

Remove contaminated clothes.

Rinse and then wash skin with

water and soap. Refer for medical

attention. Wear protective gloves

when administering first aid. See

Notes.

Eyes Redness. Pain. Safety spectacles, face shield, or

eye protection in combination with

breathing protection if powder.

First rinse with plenty of water for

several minutes (remove contact

lenses if easily possible), then take

to a doctor.

Ingestion Burning sensation in the throat

and chest. (Further see

Inhalation).

Do not eat, drink, or smoke during

work. Wash hands before eating.

Rinse mouth. Induce vomiting

(ONLY IN CONSCIOUS

PERSONS!). Refer for medical

attention. See Notes.

SPILLAGE DISPOSAL PACKAGING & LABELLING

Evacuate danger area! Consult an expert! Do NOT

wash away into sewer. Sweep spilled substance

into containers. Carefully collect remainder, then

remove to safe place. Prevent contact with water or

moist substances. Do NOT let this chemical enter

the environment. Chemical protection suit including

self-contained breathing apparatus.

T+ Symbol

R: 28-32

S: (1/2-)7/8-23-36/37-45

UN Hazard Class: 6.1

UN Pack Group: I

Airtight. Do not transport with food

and feedstuffs. Marine pollutant.

EMERGENCY RESPONSE STORAGE

Transport Emergency Card: TEC (R)-61G16a.

NFPA Code: H 3; F 0; R 0.

Fireproof. Provision to contain effluent from fire extinguishing. Separated

from strong oxidants, acids, food and feedstuffs. Dry. Well closed.
Decomposes below melting point at 350C

Density: 1.8 g/cm3

Solubility in water: reaction

LEGAL NOTICE Neither the EC nor the IPCS nor any person acting on behalf of the EC or the IPCS is responsible

© IPCS 1999

0407 CALCIUM CYANIDE

IMPORTANT DATA

Physical State; Appearance

COLOURLESS CRYSTALS OR WHITE POWDER, WITH

CHARACTERISTIC ODOUR.

Chemical Dangers

The substance decomposes on heating above 350C,

producing toxic fumes including nitrogen oxides and hydrogen

cyanide. Reacts violently with water, moist air, carbon dioxide,

acids and acid salts producing highly toxic and flammable

hydrogen cyanide. Reacts violently when heated with oxidizing

substances causing fire and explosion hazard.

Occupational Exposure Limits

TLV not established.

Routes of Exposure

The substance can be absorbed into the body by inhalation,

through the skin or by ingestion.

Inhalation Risk

Evaporation at 20C is negligible; a harmful concentration of

airborne particles can, however, be reached quickly when

dispersed.

Effects of Short-term Exposure

The substance irritates the eyes the skin and the respiratory

tract. The substance may cause effects on the intracellular

oxygen metabolism, resulting in seizures and

unconsciousness. Exposure may result in death.

Effects of Long-term or Repeated Exposure

Repeated or prolonged contact with skin may cause dermatitis.

PHYSICAL PROPERTIES

ENVIRONMENTAL DATA

The substance is very toxic to aquatic organisms.

NOTES

Depending on the degree of exposure, periodic medical examination is indicated. Specific treatment is necessary in case of

poisoning with this substance; the appropriate means with instructions must be available. No odour warning if toxic concentrations

are present. Do NOT take working clothes home.

ADDITIONAL INFORMATION
Prepared in the context of cooperation between the International

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© IPCS 2001

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CYANOGEN 1390

October 2001

CAS No: 460-19-5

RTECS No: GT1925000

UN No: 1026

EC No: 608-011-00-8

Dicyanogen

Ethanedinitrile

Oxalonitrile

(cylinder)

C2N2

Molecular mass: 52.04

TYPES OF

HAZARD/

EXPOSURE

ACUTE HAZARDS/SYMPTOMS PREVENTION FIRST AID/FIRE FIGHTING

FIRE Highly flammable. Gives off

irritating or toxic fumes (or gases)

in a fire.

NO open flames, NO sparks, and

NO smoking.

Shut off supply; if not possible and

no risk to surroundings, let the fire

burn itself out; in other cases

extinguish with dry powder, carbon

dioxide.

EXPLOSION Gas/air mixtures are explosive.

Risk of fire and explosion on

contact with strong oxidants.

Closed system, ventilation,

explosion-proof electrical equipment

and lighting.

In case of fire: keep cylinder cool by

spraying with water.

EXPOSURE AVOID ALL CONTACT! IN ALL CASES CONSULT A

DOCTOR!

Inhalation Convulsions. Cough. Dizziness.

Headache. Laboured breathing.

Sore throat. Unconsciousness.

Vomiting.

Ventilation, local exhaust, or

breathing protection.

Fresh air, rest. Half-upright position.

Artificial respiration may be needed.

No mouth-to-mouth artificial

respiration. Refer for medical

attention. See Notes.

Skin ON CONTACT WITH LIQUID:

FROSTBITE.

Cold-insulating gloves. ON FROSTBITE: rinse with plenty

of water, do NOT remove clothes.

Refer for medical attention.

Eyes Redness. Pain. Face shield, or eye protection in

combination with breathing

protection.

First rinse with plenty of water for

several minutes (remove contact

lenses if easily possible), then take

to a doctor.

Ingestion

SPILLAGE DISPOSAL PACKAGING & LABELLING

Evacuate danger area! Consult an expert!

Ventilation. Remove all ignition sources. NEVER

direct water jet on liquid. (Extra personal protection:

) gas-tight chemical protection suit including

self-contained breathing apparatus.

F Symbol

T Symbol

N Symbol

R: 11-23-50/53

S: (1/2-)23-45-60-61

UN Hazard Class: 2.3

UN Subsidiary Risks: 2.1

EMERGENCY RESPONSE STORAGE

Transport Emergency Card: TEC (R)-20G2TF

NFPA Code: H4; F4; R2

Fireproof. Cool.
Boiling point: -21.2°C

Melting point: -27.9°C

Relative density (water = 1): 0.95 at -21°C

Solubility in water, ml/100 ml at 20°C: 450

Relative vapour density (air = 1): 1.8

Flash point: Flammable Gas

Explosive limits, vol% in air: 6.6-42.6

Octanol/water partition coefficient as log Pow: 0.07

LEGAL NOTICE Neither the EC nor the IPCS nor any person acting on behalf of the EC or the IPCS is responsible

 for the use which might be made of this information

©IPCS 2001

1390 CYANOGEN

IMPORTANT DATA

Physical State; Appearance

COLOURLESS GAS OR COMPRESSED LIQUEFIED GAS,

WITH CHARACTERISTIC ODOUR.

Physical dangers

The gas is heavier than air and may travel along the ground;

distant ignition possible.

Chemical dangers

On combustion, forms toxic gases including hydrogen cyanide,

carbon monoxide, nitrogen oxides. Reacts with strong oxidants

causing fire and explosion hazard. The substance reacts with

acids forming highly toxic gases such as hydrogen cyanide.

Occupational exposure limits

TLV: 10 ppm as TWA (ACGIH 2001).

MAK: 10 ppm; 22 mg/m3

; (2000)

Routes of exposure

The substance can be absorbed into the body by inhalation.

Inhalation risk

A harmful concentration of this gas in the air will be reached

very quickly on loss of containment.

Effects of short-term exposure

The substance is irritating to the eyes and the respiratory tract.

Rapid evaporation of the liquid may cause frostbite. The

substance may cause effects on the central nervous system,

resulting in respiratory failure and collapse. Exposure far above

the OEL may result in death.

PHYSICAL PROPERTIES

ENVIRONMENTAL DATA

The substance is very toxic to aquatic organisms.

NOTES

Specific treatment is necessary in case of poisoning with this substance; the appropriate means with instructions must be available.

The odour warning when the exposure limit value is exceeded is insufficient.

Turn leaking cylinder with the leak up to prevent escape of gas in liquid state.

ADDITIONAL INFORMATION
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© IPCS 2000

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CYANOGEN CHLORIDE 1053

October 1999

CAS No: 506-77-4

RTECS No: GT2275000

UN No: 1589 (inhibited)

Chlorine cyanide

Chlorocyanide

Chlorocyanogen

(cylinder)

ClCN

Molecular mass: 61.5

TYPES OF

HAZARD/

EXPOSURE

ACUTE HAZARDS/SYMPTOMS PREVENTION FIRST AID/FIRE FIGHTING

FIRE Not combustible. Heating will

cause rise in pressure with risk of

bursting. Gives off irritating or toxic

fumes (or gases) in a fire.

In case of fire in the surroundings:

all extinguishing agents allowed.

EXPLOSION In case of fire: cool cylinder by

spraying with water but avoid

contact of the substance with water.

EXPOSURE AVOID ALL CONTACT!

Inhalation Sore throat. Drowsiness.

Confusion. Nausea. Vomiting.

Cough. Unconsciousness.

Symptoms may be delayed (see

Notes).

Local exhaust or breathing

protection.

Fresh air, rest. Half-upright position.

Artificial respiration if indicated.

Refer for medical attention.

Skin ON CONTACT WITH LIQUID:

FROSTBITE. THE LIQUID MAY

BE ABSORBED. Redness. Pain.

Cold-insulating gloves. Protective

clothing.

ON FROSTBITE: rinse with plenty

of water, do NOT remove clothes.

Refer for medical attention.

Eyes ON CONTACT WITH LIQUID:

FROSTBITE. Redness. Pain.

Face shield, or eye protection in

combination with breathing

protection.

First rinse with plenty of water for

several minutes (remove contact

lenses if easily possible), then take

to a doctor.

Ingestion Do not eat, drink, or smoke during

work.

SPILLAGE DISPOSAL PACKAGING & LABELLING

Evacuate danger area! Consult an expert!

Ventilation. NEVER direct water jet on liquid.

Remove vapour cloud with fine water spray. Do

NOT wash away into sewer. Chemical protection

suit including self-contained breathing apparatus.

UN Hazard Class: 2.3

UN Subsidiary Risks: 8

Marine pollutant.

EMERGENCY RESPONSE STORAGE

Transport Emergency Card: TEC (R)-801 Fireproof if in building. Provision to contain effluent from fire extinguishing.

Cool.
Boiling point: 13.8°C

Melting point: -6°C

Solubility in water: soluble

Vapour pressure, kPa at 21.1°C: 1987

Relative vapour density (air = 1): 2.16

LEGAL NOTICE Neither the EC nor the IPCS nor any person acting on behalf of the EC or the IPCS is responsible

 for the use which might be made of this information

©IPCS 2000

1053 CYANOGEN CHLORIDE

IMPORTANT DATA

Physical State; Appearance

COLOURLESS COMPRESSED LIQUEFIED GAS, WITH

PUNGENT ODOUR.

Physical dangers

The gas is heavier than air.

Chemical dangers

The substance decomposes on heating producing toxic and

corrosive fumes (hydrogen cyanide, hydrochloric acid, nitrogen

oxides). Reacts slowly with water or water vapour to form

hydrogen chloride.

Occupational exposure limits

TLV: 0.3 ppm; as (ceiling value) (ACGIH 1999).

Routes of exposure

The substance can be absorbed into the body by inhalation.

Inhalation risk

A harmful concentration of this gas in the air will be reached

very quickly on loss of containment.

Effects of short-term exposure

Tear drawing. The substance severely irritates the eyes, the

skin and the respiratory tract. The substance may cause effects

on the cellular respiration, resulting in convulsions and

unconsciousness. Exposure may result in death. Medical

observation is indicated. See Notes. Inhalation of the substance

may cause lung oedema (see Notes). The effects may be

delayed. Rapid evaporation of the liquid may cause frostbite.

Medical observation is indicated.

PHYSICAL PROPERTIES

ENVIRONMENTAL DATA

The substance is very toxic to aquatic organisms.

NOTES

The occupational exposure limit value should not be exceeded during any part of the working exposure.

The symptoms of lung oedema often do not become manifest until a few hours have passed and they are aggravated by physical

effort. Rest and medical observation is therefore essential.

Immediate administration of an appropriate spray, by a doctor or a person authorized by him/her, should be considered.

Specific treatment is necessary in case of poisoning with this substance; the appropriate means with instructions must be available.

Do NOT spray water on leaking cylinder (to prevent corrosion of cylinder).

Turn leaking cylinder with the leak up to prevent escape of gas in liquid state.

ADDITIONAL INFORMATION
Prepared in the context of cooperation between the International

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© IPCS 1999

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Chemical Safety

ACETONE CYANOHYDRIN 0611

March 1998

CAS No: 75-86-5

RTECS No: OD9275000

UN No: 1541

EC No: 608-004-00-X

2-Hydroxy-2-methyl propionitrile

2-Methyl-lactonitrile

2-Cyanopropan-2-ol

p-Hydroxyisobutyronitrile

(CH3)2C(OH)CN / C4H7NO

Molecular mass: 85.1

TYPES OF

HAZARD/

EXPOSURE

ACUTE HAZARDS/SYMPTOMS PREVENTION FIRST AID/FIRE FIGHTING

FIRE Combustible. Gives off irritating or

toxic fumes (or gases) in a fire.

NO open flames. Powder, AFFF, foam, carbon

dioxide.

EXPLOSION Above 74C explosive vapour/air

mixtures may be formed.

Above 74C use a closed system,

ventilation.

In case of fire: cool drums, etc., by

spraying with water but avoid

contact of the substance with water.

Combat fire from a sheltered

position.

EXPOSURE AVOID ALL CONTACT! IN ALL CASES CONSULT A

DOCTOR!

Inhalation Convulsions. Cough. Dizziness.

Headache. Laboured breathing.

Nausea. Shortness of breath.

Unconsciousness. Vomiting.

Irregular heartbeat, tightness in

the chest.

Closed system and ventilation. Fresh air, rest. Half-upright

position. Artificial respiration if

indicated. Refer for medical

attention.

Skin MAY BE ABSORBED! Redness.

Pain (See Inhalation).

Protective gloves. Protective

clothing.

Rinse and then wash skin with

water and soap. Refer for medical

attention.

Eyes Redness. Pain. Face shield, or eye protection in

combination with breathing

protection.

First rinse with plenty of water for

several minutes (remove contact

lenses if easily possible), then take

to a doctor.

Ingestion Abdominal cramps. Burning

sensation. Convulsions.

Unconsciousness. See Notes (see

Inhalation).

Do not eat, drink, or smoke during

work.

Rinse mouth. Refer for medical

attention.

SPILLAGE DISPOSAL PACKAGING & LABELLING

Sweep spilled substance into containers. Carefully

collect remainder, then remove to safe place. Do

NOT let this chemical enter the environment (extra

personal protection: complete protective clothing

including self-contained breathing apparatus).

T+ Symbol

N Symbol

R: 26/27/28-50

S: (1/2-)7/9-27-45-61

UN Hazard Class: 6.1

UN Pack Group: I

Airtight. Do not transport with food

and feedstuffs. Marine pollutant.

EMERGENCY RESPONSE STORAGE

Transport Emergency Card: TEC (R)-172

NFPA Code: H4; F1; R2

Provision to contain effluent from fire extinguishing. Separated from strong

bases, acids, water, food and feedstuffs. Well closed. Keep in a

well-ventilated room.
Boiling point: 95C

Melting point: -19C

Relative density (water = 1): 0.93

Solubility in water: freely soluble, but decomposes in water

Vapour pressure, kPa at 20C: 3.0

Relative vapour density (air = 1): 2.93

Flash point: 74C c.c. 

Explosive limits, vol% in air: 2.2-12

LEGAL NOTICE Neither the EC nor the IPCS nor any person acting on behalf of the EC or the IPCS is responsible

 for the use which might be made of this information

© IPCS 1999

0611 ACETONE CYANOHYDRIN

IMPORTANT DATA

Physical State; Appearance

COLOURLESS LIQUID, WITH CHARACTERISTIC ODOUR.

Physical Dangers

The vapour is heavier than air.

Chemical Dangers

The substance decomposes rapidly on heating or on contact

with bases or water, producing highly toxic and flammable

hydrogen cyanide (see ICSC # 0492), and acetone (see ICSC #

0087). Reacts violently with acids and oxidants causing fire and

explosion hazard.

Occupational Exposure Limits

TLV: 4.7 ppm; 5 mg/m3 (ceiling values) as CN (skin) (ACGIH

1997).

Routes of Exposure

The substance can be absorbed into the body by inhalation,

through the skin and by ingestion.

Inhalation Risk

A harmful contamination of the air can be reached rather

quickly on evaporation of this substance at 20C.

Effects of Short-term Exposure

The substance irritates the eyes, the skin and the respiratory

tract. The substance may cause effects on the cardiovascular

system and central nervous system, resulting in asphyxia,

cardiac disorders, convulsions, cyanosis and respiratory

failure. Exposure may result in death. Medical observation is

indicated. See Notes.

Effects of Long-term or Repeated Exposure

The substance may have effects on the central nervous system

and thyroid, resulting in impaired functions.

PHYSICAL PROPERTIES

ENVIRONMENTAL DATA

The substance is very toxic to aquatic organisms. Avoid release to the environment in circumstances different to normal use.

NOTES

Specific treatment is necessary in case of poisoning with this substance; the appropriate means with instructions must be

available. Hazard and toxicity of this substance is due to its major metabolite - hydrogen cyanide (see ISCS # 0492).

ADDITIONAL INFORMATION
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POTASSIUM FERRICYANIDE 1132

October 2002

CAS No: 13746-66-2

RTECS No: LJ8225000

Tripotassium hexacyanoferrate (-3)

Potassium cyanoferrate

Potassium ferricyanate

Iron potassium cyanide

C6FeK3N6 / K3Fe(CN)6

Molecular mass: 329.25

TYPES OF

HAZARD/

EXPOSURE

ACUTE HAZARDS/SYMPTOMS PREVENTION FIRST AID/FIRE FIGHTING

FIRE Not combustible. Gives off irritating

or toxic fumes (or gases) in a fire.

In case of fire in the surroundings:

use appropriate extinguishing

media.

EXPLOSION

EXPOSURE

Inhalation Cough. Sore throat. Avoid inhalation of dust. Fresh air, rest.

Skin Redness. Pain. Protective gloves. Remove contaminated clothes.

Rinse skin with plenty of water or

shower.

Eyes Redness. Pain. Safety spectacles. First rinse with plenty of water for

several minutes (remove contact

lenses if easily possible), then take

to a doctor.

Ingestion Abdominal pain. Nausea.

Vomiting.

Do not eat, drink, or smoke during

work.

Rinse mouth. Give plenty of water

to drink.

SPILLAGE DISPOSAL PACKAGING & LABELLING

Sweep spilled substance into containers; if

appropriate, moisten first to prevent dusting.

Carefully collect remainder, then remove to safe

place. Do NOT let this chemical enter the

environment. (Extra personal protection: P2 filter

respirator for harmful particles.)

EMERGENCY RESPONSE STORAGE

Separated from acids. Dry.
Density: 1.89 g/cm3 Solubility in water, g/100 ml: 46

LEGAL NOTICE Neither the EC nor the IPCS nor any person acting on behalf of the EC or the IPCS is responsible

 for the use which might be made of this information

©IPCS 2002

1132 POTASSIUM FERRICYANIDE

IMPORTANT DATA

Physical State; Appearance

RED CRYSTALLINE POWDER

Chemical dangers

The substance decomposes on heating producing toxic gases

including hydrogen cyanide. Reacts with acids, to produce

cyanides, causing toxic hazard.

Occupational exposure limits

TLV not established.

Routes of exposure

The substance can be absorbed into the body by inhalation and

by ingestion.

Inhalation risk

A nuisance-causing concentration of airborne particles can be

reached quickly when dispersed, especially if powdered.

Effects of short-term exposure

The substance is mildly irritating to the eyes, the skin and the

respiratory tract.

PHYSICAL PROPERTIES

ENVIRONMENTAL DATA

This substance may be hazardous in the environment; special attention should be given to aquatic organisms.

NOTES

Temperature of decomposition unknown in literature.

Health effects of exposure to the substance have not been investigated adequately.

ADDITIONAL INFORMATION
Concise International Chemical Assessment Document 61 

62 

RÉSUMÉ D’ORIENTATION 

 Le présent CICAD relatif au cyanure d’hydrogène 

(acide cyanhydrique) et aux cyanures (aspects touchant 

la santé humaine) a été préparé par le Pr Fina Petrova 

Simeonova et le Dr Lawrence Fishbein, principalement 

sur la base du profil toxicologique des cyanures établi 

par l’Agency for Toxic Substances and Disease Registry 

(ATSDR, 1997) et d’un document du Comité mixte 

FAO/OMS d’experts des additifs alimentaires portant 

sur les glucosides cyanogéniques (JECFA, 1993). 

L’appendice 1 est consacré à ces documents de base 

ainsi qu’à la manière dont ils ont été passés en revue. En 

octobre 2002, il a été procédé à un dépouillement 

exhaustif de la bibliographie contenue dans plusieurs 

bases de données en ligne à la recherche d’articles 

publiés postérieurement à ceux qui sont cités dans les 

documents de base. Ce CICAD a fait l’objet d’un 

premier examen lors de la dixième réunion du Comité 

d’évaluation finale qui s’est tenue à Monks Wood 

(Royaume-Uni) du 16 au 19 septembre 2002. Après 

avoir été révisé, il a été réexaminé et approuvé en tant 

qu’évaluation internationale lors de la onzième réunion 

du Comité d’évaluation finale qui a eu lieu à Varna 

(Bulgarie) du 8 au 11 septembre 2003. La liste des 

participants à la dixième et à la onzième réunion du 

Comité d’évaluation finale figure aux appendices 2 et 3. 

Les documents préparatoires discutés lors de ces 

réunions avaient été préalablement examinés par des 

pairs; des renseignements sur ces examens sont donnés à 

l’appendice 4. Les fiches internationale sur la sécurité 

chimique du cyanure d’hydrogène, du cyanure de 

sodium, du cyanure de potassium, du cyanure de 

calcium, du cyanogène, du chlorure de cyanogène, de la 

cyanhydrine d’acétone - plus couramment appelée 

acétone cyanhydrine - et du ferricyanure de potassium 

établies par le Programme international sur la sécurité 

chimique (IPCS, 1999a,b, 2000b, 2001, 2002a,b,c,d) 

sont également reproduites dans le présent document. 

 On désigne sous le nom de cyanures des composés 

très divers et de complexité chimique variable, mais qui 

contiennent tous un groupement CN et auxquels 

l’Homme peut se trouver exposé lorsqu’ils sont produits 

à l’état gazeux, liquide ou solide par toutes sortes de 

sources naturelles ou anthropogéniques. Différents types 

de cyanures sont utilisés dans un certain nombre 

d’applications industrielles ou sont présents dans 

l’environnement, mais quelle qu’en soit l’origine, c’est 

l’anion cyanure CN–

 qui représente l’agent toxique 

essentiel. 

 Le cyanure d’hydrogène se présente sous la forme 

d’un liquide ou d’un gaz incolore à bleu pâle dégageant 

une légère odeur d’amande amère. On l’utilise 

principalement pour la préparation de substances telles 

que l’adiponitrile, le méthacrylate de méthyle, divers 

agents chélatants, le chlorure cyanurique (2,4,6-

trichlorotriazine), la méthionine et ses analogues 

hydroxylés, ainsi que le cyanure de potassium et le 

cyanure de sodium. On s’en sert également comme 

fumigant à l’intérieur des navires, des voitures de 

chemin de fer, des grands bâtiments, des silos à grain et 

des minoteries ainsi que pour traiter les pois et les 

semences en chambre étanche. 

 D’autres cyanures, comme le cyanure de potassium 

et le cyanure de sodium se présentent sous la forme de 

sels solides ou de cristaux hygroscopiques dont on fait 

grand usage pour extraire l’or et l’argent de leurs 

minerais, en galvanoplastie, pour la cémentation de 

l’acier, la flottation des métaux de base et le dégraissage 

des métaux, la teinture, l’impression et la photographie. 

Ils sont également très largement utilisés pour la 

synthèse de composés organiques ou minéraux (comme 

les nitriles, les acides carboxyliques, les amides, les 

esters et les amines ou les cyanures de métaux lourds) 

ainsi que pour la production d’agents chélatants. 

 Il existe différentes sources anthropogéniques qui 

libèrent des cyanures dans l’environnement. Ils peuvent 

par exemple être rejetés dans l’atmosphère par les 

industries qui les produisent ou les utilisent à diverses 

fins, comme les industries métallurgiques et celles qui 

pratiquent la galvanoplastie ou l’extraction de l’or et de 

l’argent à partir de minerais à faible teneur. Ils peuvent 

également s’échapper dans l’environnement par 

volatilisation à partir de déchets enfouis dans des 

décharges ou rejetés dans des bassins, émission à partir 

d’incinérateurs municipaux qui brûlent des déchets 

solides, combustion de biomasse ou de combustibles 

fossiles (notamment dans les gaz d’échappement des 

véhicules à moteur), lors d’opérations de fumigation ou 

encore pendant la production de coke ou autres 

opérations de carbonisation de la houille. 

 Il se forme du cyanure d’hydrogène lors de la 

combustion incomplète des polymères azotés, comme 

certains plastiques, les polyuréthanes et la laine. La 

fumée de cigarette en contient également. 

 Les cyanures qui passent dans le compartiment 

aquatique à partir de sources non ponctuelles peuvent 

être transportés par les eaux de ruissellement contenant 

des sels antiagglomérants cyanurés épandus sur les 

routes, provenir de déchets enfouis ou encore du 

lessivage de divers dépôts d’origine agricole ou 

atmosphérique. Au nombre des sources ponctuelles de 

cyanures figurent les installations d’extraction de l’or, 

les usines de traitement de l’eau, la sidérurgie et 

l’industrie chimique organique. 

 On compte plus de 2000 espèces végétales 

(notamment des fruits et des légumes) contenant des 

glucosides cyanogéniques qui constituent des sources 
Hydrogen cyanide and cyanides: Human health aspects 

63 

naturelles de cyanures et qui sont capables de libérer des 

ions cyanure par hydrolyse lorsqu’ils sont ingérés. Parmi 

ces denrées, on peut citer la cassave (tapioca, manioc) et 

le sorgho qui, dans de nombreux pays tropicaux, 

représentent l’alimentation de base de millions de gens. 

L’amygdaline, la linamarine, la prunasine, la dhurrine, la 

lotaustraline et la taxiphylline sont des glucosides 

cyanogéniques bien connus. Certains processus 

biologiques qui se déroulent dans les plantes supérieures, 

les champignons et les bactéries conduisent également à 

la libération de cyanures dans l’atmosphère. 

 Dans l’air, les cyanures sont présent sous la forme 

de cyanure d’hydrogène gazeux, avec une petite fraction 

sous forme de fines particules de poussière. Les 

cyanures sont susceptibles d’être transportés sur de 

longues distances à partir de leur source d’émission. 

 Dans sa majorité, la population n’est exposée qu’à 

de très faibles quantités de cyanures présents dans 

l’environnement général. Toutefois, pour certains 

groupes, la possibilité d’exposition est plus grande. Il 

s’agit notamment de personnes qui travaillent à la 

transformation à grande échelle du manioc ou qui 

consomment des quantités importantes d’aliments mal 

préparés contenant des glucosides cyanogéniques, 

comme le manioc ou encore certaines denrées 

particulières comme les noyaux d’abricots et les 

amandes amères. Parmi les autres groupes de population 

qui risquent le plus d’être exposés aux cyanures, on peut 

citer les personnes qui résident à proximité de sources 

ponctuelles à partir desquelles ces substances peuvent 

être libérées volontairement ou accidentellement dans 

l’environnement, les fumeurs actifs et passifs ou encore 

les personnes qui ont inhalé de la fumée à la suite d’un 

incendie. 

 Les travailleurs peuvent être exposés aux cyanures 

au cours d’opérations de fumigation, lors de la 

production de ces substances ou encore lors de 

nombreuses activités industrielles au cours desquelles 

elles sont utilisées - par exemple lors d’opérations de 

galvanoplastie ou de cémentation de l’acier ou lors de 

l’extraction de l’or et de l’argent de leurs minerais. 

 Bien résorbés au niveau des voies digestives ou par 

passage transcutané, les cyanures sont rapidement 

absorbés par la voie respiratoire. Une fois absorbés, ils 

se répandent rapidement dans tout l’organisme, mais les 

teneurs les plus élevées sont habituellement retrouvées 

au niveau du foie, des poumons, dans le sang et dans 

l’encéphale. Une exposition chronique ou répétée ne 

provoque pas d’accumulation de cyanures dans le sang 

ou les tissus. 

 Une fois absorbés, les cyanures sont métabolisés 

dans la proportion d’environ 80 % en thiocyanates au 

niveau du foie sous l’action d’une sulfo-transférase 

mitochondriale, la rhodanase, et d’autres sulfotransférases. Les thiocyanates sont excrétés dans les 

urines. Il existe des voies métaboliques mineures de 

détoxication des cyanures qui comportent une réaction 

avec la cystine conduisant aux acides aminothiazolineet iminothiazolidinecarboxyliques ou une combinaison 

avec l’hydroxycobalamine (vitamine B12a) conduisant à 

la formation de cyanocobalamine (vitamine B12). Ces 

produits finals sont également excrétés par la voie 

urinaire. 

 Les cyanures sont principalement caractérisés par 

une toxicité élevée quelle que soit la voie d’administration, avec une courbe dose-effet à très forte pente 

dépendant de la vitesse d’administration, ainsi que par 

une toxicité chronique dans laquelle intervient probablement l’ion thiocyanate, qui est leur principal métabolite 

et produit de détoxication. Les effets toxiques de l’ion 

cyanure sont généralement similaires chez l’Homme et 

l’animal et on pense qu’ils sont dus à l’inactivation de la 

cytochrome-oxydase qui conduit à l’inhibition de la 

respiration et à une anoxie histotoxique. Les principales 

cibles de l’action toxique de l’ion cyanure sont les 

appareils cardiovasculaire et respiratoire ainsi que le 

système nerveux central. Le système endocrinien est 

également une cible potentielle de l’activité toxique à 

long terme de l’ion cyanure, qui résulte d’une exposition 

permanente à l’ion thiocyanate ayant pour effet d’inhiber 

la fixation de l’iode par la thyroïde et par suite, de 

conduire à la formation d’un goitre. 

 Chez l’Homme, si de légers effets peuvent être 

notés aux doses de 20 à 40 mg/m3

, des doses de 50 à 60 

mg/m3 sont supportables pendant 20 minutes à 1 heure 

sans effets immédiats ou retardés. Une dose de l’ordre de 

120 à 150 mg/m3

 peut entraîner la mort au bout d’une 

demi-heure à une heure et à partir de 150 mg/m3

, la mort 

peut survenir en l’espace de 30 minutes. Une exposition 

à 200 mg/m3

 est probablement mortelle au bout de 

10 minutes et à partir de 300 mg/m3

, la mort est 

immédiate. Chez l’Homme, la dose la plus faible qui se 

soit révélée mortelle par voie orale est de 0,54 mg/kg de 

poids corporel et on estime que dans les cas d’empoisonnement, la dose moyenne absorbée au moment de la 

mort est de 1,4 mg/kg p.c. (calculée en cyanure d’hydrogène). Après une intoxication grave, les séquelles 

peuvent être de nature neuropsychiatrique ou de type 

parkinsonien. On estime que les cyanures présents dans 

la fumée de tabac contribuent à l’amblyopie alcoolotabagique. Une exposition prolongée à de faibles 

concentrations de cyanures sur le lieu de travail peut 

déterminer divers symptômes neurologiques centraux. 

 On attribue à la consommation prolongée de manioc 

riche en glucosides cyanogéniques diverses pathologies 

telles que la neuropathie ataxique tropicale ou la 
Concise International Chemical Assessment Document 61 

64 

paraparésie spastique et, dans les régions où l’apport 

d’iode est insuffisant, l’hypothyroïdie, le goitre et le 

crétinisme. Si l’on a pu quelquefois estimer l’exposition 

journalière aux cyanures dans les régions d’endémie à 

approximativement 15-50 mg, le caractère limité des 

informations sur l’exposition et l’influence possible de 

facteurs de confusion comme la malnutrition, la faible 

teneur en protéines de l’alimentation, les carences 

vitaminiques et l’insuffisance du bilan iodé font que les 

données ne permettent pas d’obtenir des renseignements 

valables sur la relation dose-réponse dans le cas des 

cyanures. 

 Les données concernant des points d’aboutissement 

de l’action toxique autres que la toxicité aiguë sont assez 

limitées. On peut attribuer pour une grande part cet état 

de choses à la difficulté d’effectuer, par exemple, des 

études avec des doses répétées ou des études de toxicité 

chronique sur une substance présentant une toxicité 

aiguë aussi forte. Les cyanures sont légèrement irritants 

pour la peau et la muqueuse oculaire. On n’a pas trouvé 

de données concernant d’éventuelles propriétés 

sensibilisantes ou une quelconque activité cancérogène 

de l’acide cyanhydrique ou de ses sels alcalins. Les 

éléments d’appréciation dont on dispose sont quelque 

peu limités, mais montrent cependant que les cyanures 

ne sont pas génotoxiques et qu’ils ne produisent d’effets 

sur le développement qu’à des doses toxiques pour la 

mère. 

 Les données relatives aux populations humaines ne 

sont pas suffisantes pour servir de base à la caractérisation de la relation dose-réponse dans le cas d’une 

ingestion chronique de cyanures. Lors d’une étude de 

13 semaines au cours de laquelle on a administré à 

plusieurs reprises à des rats et à des souris du cyanure 

dissous dans leur eau de boisson, on n’a pas observé de 

signes neurologiques centraux ni d’effets histopathologiques au niveau de l’encéphale ou de la thyroïde 

lorsque les animaux on reçu des doses journalières de 

cette substance allant respectivement jusqu’à 12,5 et 

26 mg par kg de poids corporel. A la dose journalière de 

12,5 mg/kg p.c., on a noté de petites anomalies au niveau 

des voies génitales chez rats mâles, anomalies qui, si elle 

n’avaient apparemment pas d’effet sur la fécondité des 

animaux, ne seraient peut-être pas négligeables chez 

l’Homme. La dose journalière sans effet nocif 

observable (NOAEL) pour ce type d’effets était de 

4,5 mg/kg de poids corporel. Les examens neurologiques 

effectués dans le cadre de cette étude se sont limités à 

des observations cliniques et à un examen au microscope 

optique lors de l’autopsie. Les rares études existantes qui 

soient spécialement consacrées à l’investigation de la 

neurotoxicité, font état d’effets nocifs chez le rat à la 

dose journalière de 1,2 mg de cyanure/kg de poids 

corporel et à celle de 0,48 mg/kg chez la chèvre, mais 

elles souffrent de faiblesses qui empêchent d’en tirer des 

conclusions quantitatives. 

 Lors de trois études distinctes effectuées sur des rats 

dans le but de caractériser la relation dose-réponse dans 

le cas de l’inhalation répétée de cyanure d’hydrogène 

(principalement sur le lieu de travail), on n’a pas relevé 

d’effet toxique général chez les animaux exposés à de 

l’acétone cyanhydrine, composé qui est rapidement 

hydrolysé en cyanure d’hydrogène au pH physiologique, 

pour des concentrations allant jusqu’à 211 mg/m3 (soit 

l’équivalent de 67 mg de cyanure d’hydrogène par m3

). 

La mortalité de 30 % observée chez les rats exposés une 

partie de la journée à 225 mg/m3

 d’acétone cyanhydrine 

(soit l’équivalent de 71 mg cyanure d’hydrogène par m3

) 

traduit la forte pente de la courbe dose-effet. 

 Il est peu probable que l’exposition à la faible concentration de cyanures habituellement présents dans 

l’environnement général (< 1 μg/m3

 dans l’air ambiant; 

< 10 μg/litre dans l’eau) ait des effets nocifs. Des 

intoxications aiguës par les cyanures peuvent se produire 

à la suite de la consommation de noyaux d’abricots, de 

cerises de Virginie ou d’autres drupes riches en glucosides cyanogéniques. Du manioc mal préparé peut être 

dangereux lorsqu’il constitue l’essentiel de l’alimentation.
Hydrogen cyanide and cyanides: Human health aspects 

65 

RESUMEN DE ORIENTACIÓN 

Este CICAD sobre el cianuro de hidrógeno y otros 

cianuros (aspectos relativos a la salud humana), 

preparado por la Profesora Petrova Simeonova y el Dr. 

Lawrence Fishbein, se basó principalmente en el perfil 

toxicológico de los cianuros de la Agencia para el 

Registro de Sustancias Tóxicas y Enfermedades 

(ATSDR, 1997) y el documento sobre glucósidos 

cianogénicos del Comité Mixto FAO/OMS de Expertos 

en Aditivos Alimentarios (JECFA, 1993). Los 

documentos originales y la descripción de sus procesos 

de examen se presentan en el apéndice 1. En octubre de 

2002 se realizó una búsqueda bibliográfica amplia de 

varias bases de datos en línea para localizar cualquier 

referencia pertinente publicada después de las citadas en 

los documentos originales. Este CICAD se debatió en 

primer lugar en la 10a reunión de la Junta de Evaluación 

Final, celebrada en Monks Wood (Reino Unido) del 16 

al 19 de septiembre de 2002. Tras la revisión, se debatió 

de nuevo y se aprobó como evaluación internacional en 

la 11a reunión de la Junta de Evaluación Final, celebrada 

en Varna (Bulgaria) del 8 al 11 de septiembre de 2003. 

Las listas de participantes en las reuniones 10a y 11a de 

la Junta de Evaluación Final figuran en los apéndices 2 y 

3. Los proyectos debatidos fueron objeto de un examen 

colegiado antes de dichas reuniones; la información 

sobre el proceso del examen colegiado aparece en el 

apéndice 4. También se reproducen en este documento 

las Fichas internacionales de seguridad química para el 

cianuro de hidrógeno, el cianuro de sodio, el cianuro de 

potasio, el cianuro de calcio, el cianógeno, el cianuro de 

cloro, la cianohidrina de acetona y el ferricianuro de 

potasio, preparadas por el Programa Internacional de 

Seguridad de las Sustancias Químicas (IPCS, 1999a,b, 

2000b, 2001, 2002a,b,c,d). 

Los cianuros comprenden una amplia gama de 

compuestos con distintos grados de complejidad 

química, que se caracterizan por contener todos ellos un 

grupo CN, a los cuales están expuestas las personas ya 

sea en forma gaseosa, liquida o sólida a partir de fuentes 

naturales y antropogénicas. Si bien hay muchas formas 

químicas de cianuro que se utilizan en aplicaciones 

industriales o están presentes en el medio ambiente, el 

agente tóxico principal, con independencia del origen, es 

el anión cianuro (CN–

). 

El cianuro de hidrógeno es un líquido o gas incoloro 

o de tono azul pálido con un ligero olor a almendras 

amargas. Se utiliza fundamentalmente en la producción 

de diversas sustancias, por ejemplo adiponitrilo, 

metacrilato de metilo, agentes quelantes, cianuro de 

cloro, metionina y sus compuestos análogos hidroxilados 

y cianuro de sodio y de potasio. También se utiliza como 

fumigante en embarcaciones, vagones de ferrocarril, 

edificios grandes, silos de cereales y molinos de harina, 

así como para la fumigación de guisantes y semillas en 

cámaras de vacío. 

Otros cianuros, como los de sodio y potasio, son 

sales higroscópicas sólidas o cristalinas que se utilizan 

ampliamente en los procesos de extracción de minerales 

para la recuperación del oro y la plata, la galvanoplastia, 

el endurecimiento superficial del acero, la flotación de 

metales no preciosos, el desengrasado, teñido e 

impresión de metales y la fotografía. También se utilizan 

con frecuencia en la síntesis de sustancias químicas 

orgánicas e inorgánicas (por ejemplo, nitrilos, ácidos 

carboxílicos, amidas, ésteres y aminas; cianuros de 

metales pesados) y en la producción de agentes 

quelantes. 

El cianuro que se libera en el medio ambiente 

procede de fuentes antropogénicas diversas. Las 

emisiones al aire se deben a las industrias de fabricación 

y elaboración de productos químicos, como las 

metalúrgicas y de chapado metálico, y la extracción de 

oro y plata a partir de minerales de baja calidad. Otras 

fuentes son la volatilización de los desechos de cianuro 

existentes en los vertederos y estanques utilizados para 

su eliminación, las emisiones de los incineradores 

municipales de residuos sólidos, la combustión de 

biomasa, el consumo de combustibles fósiles, en 

particular las emisiones de los vehículos, las operaciones 

de fumigación y la producción de coque u otros 

procedimientos de carbonización del carbón. 

Se forma cianuro de hidrógeno durante la 

combustión incompleta de polímeros que contienen 

nitrógeno, como ciertos plásticos, poliuretanos y lana. 

También está presente en el humo de los cigarrillos. 

Puede haber fuentes no puntuales de emisiones de 

cianuro al agua a partir de la escorrentía de sales 

antiaglutinantes con cianuro utilizadas en las carreteras, 

la migración desde los vertederos y el arrastre y lavado 

de los cultivos agrícolas y de la atmósfera. Entre las 

fuentes puntuales de emisiones al agua están las 

descargas de instalaciones de extracción de oro, las 

operaciones de tratamiento de las aguas residuales, la 

producción de hierro y acero y otras industrias de 

fabricación de productos químicos orgánicos. 

Las principales fuentes naturales de cianuro son más 

de 2000 especies de plantas, con inclusión de frutas y 

hortalizas, que contienen glucósidos cianogénicos, que 

cuando se ingieren pueden liberar cianuro por hidrólisis. 

Entre ellas, la yuca (tapioca, mandioca) y el sorgo son 

alimentos básicos de cientos de millones de personas en 

numerosos países tropicales. Son glucósidos cianogénicos conocidos de plantas la amigdalina, la linamarina, la prunasina, la durrina, la lotaustralina y la 
Concise International Chemical Assessment Document 61 

66 

taxifilina. Los procesos biogénicos naturales de las 

plantas superiores, las bacterias y los hongos desprenden 

cianuro de hidrógeno en la atmósfera. 

El cianuro está presente en el aire como cianuro de 

hidrógeno gaseoso, con una pequeña cantidad en 

partículas finas de polvo. Los cianuros pueden recorrer 

largas distancias desde sus respectivas fuentes de 

emisión. 

La mayoría de la población está expuesta a niveles 

muy bajos de cianuro en el medio ambiente general. Sin 

embargo, hay subgrupos específicos con un potencial 

más elevado de exposición. Entre ellos figuran las 

personas que intervienen en la elaboración de la yuca en 

gran escala o quienes consumen cantidades importantes 

de alimentos que contienen glucósidos cianogénicos 

preparados de manera inadecuada, como la yuca y 

alimentos especiales, como los huesos de albaricoque y 

las almendras amargas. Otros subgrupos con un gran 

potencial de exposición son los que se encuentran en las 

cercanías de emisiones accidentales o intencionadas de 

fuentes puntuales, los fumadores activos y pasivos y las 

víctimas de inhalación del humo a causa de incendios. 

Los trabajadores pueden estar expuestos a los 

cianuros durante las operaciones de fumigación y 

durante la producción y utilización de cianuros en 

numerosos procesos industriales, por ejemplo la 

galvanoplastia, el endurecimiento superficial del acero y 

la extracción de oro y plata de los minerales. 

Los cianuros se absorben bien a través del tracto 

gastrointestinal o la piel y con gran rapidez en el tracto 

respiratorio. Una vez absorbido, se distribuye de manera 

rápida y ubicua por todo el organismo, aunque las 

concentraciones más elevadas se suelen encontrar en el 

hígado, los pulmones, la sangre y el cerebro. No hay 

acumulación de cianuro en la sangre o los tejidos tras la 

exposición crónica o repetida. 

La rodanasa, enzima sulfotransferasa mitocondrial, 

y otras sulfotransferasas metabolizan en el hígado a 

tiocianato alrededor del 80% del cianuro absorbido. El 

tiocianato se excreta en la orina. Son vías secundarias 

para la desintoxicación del cianuro la reacción con la 

cistina para formar los ácidos aminotiazolincarboxílico e 

iminotiazolidincarboxílico y la combinación con la 

hidroxicobalamina (vitamina B12a) para forrmar cianocobalamina (vitamina B12); estos productos finales 

también se excretan en la orina. 

Las principales características del perfil toxicológico del cianuro son su elevada toxicidad aguda por 

todas las vías de administración, con una curva de la 

relación dosis-efecto de pendiente muy pronunciada y 

dependiente de la tasa de aplicación, y su toxicidad 

crónica, probablemente mediada por el tiocianato, 

metabolito principal y producto de la desintoxicación. 

Los efectos tóxicos del ión cianuro en las personas y los 

animales son en general semejantes y parece que se 

deben a la inactivación de la citocromo oxidasa y la 

inhibición de la respiración celular y la consiguiente 

anoxia histotóxica. La toxicidad del cianuro en las 

personas y los animales afecta fundamentalmente a los 

sistemas cardiovascular, respiratorio y nervioso central. 

El sistema endocrino también puede verse afectado por 

la toxicidad prolongada, debido a la exposición 

continuada al tiocianato, que impide la absorción de 

yodo en el tiroides y actúa como agente bociógeno. 

En las personas, si bien con niveles de exposición 

de 20-40 mg/m3

 se pueden producir efectos ligeros, son 

tolerables sin efectos inmediatos o tardíos concentraciones de 50-60 mg/m3

 durante un intervalo de 20 minutos a una hora, 120-150 mg/m3

 pueden provocar la 

muerte tras un intervalo de 0,5 a una hora, 150 mg/m3

probablemente son mortales en 30 minutos, 200 mg/m3

probablemente son mortales después de 10 minutos y 

300 mg/m3

 son mortales de manera inmediata. La dosis 

letal más baja por vía oral notificada en personas es de 

0,54 mg/kg de peso corporal y la dosis media absorbida 

en el momento de la muerte se ha estimado en 1,4 mg/kg 

de peso corporal (calculada como cianuro de hidrógeno). 

Entre las secuelas que aparecen tras una intoxicación 

aguda grave figuran manifestaciones neuropsiquiátricas 

y una enfermedad del tipo del Parkinson. Se ha señalado 

que el cianuro del humo del tabaco es un factor que 

contribuye a la ambliopía debida al alcohol y el tabaco. 

La exposición prolongada a concentraciones más bajas 

de cianuro en los entornos ocupacionales puede provocar 

diversos síntomas relacionados con efectos en el sistema 

nervioso central. 

El consumo prolongado de yuca, que contiene 

niveles elevados de glucósidos cianogénicos, se ha 

relacionado con la presencia de neuropatía atáxica 

tropical y paraparesia espástica y, en zonas con un 

consumo bajo de yodo, la aparición de hipotiroidismo, 

bocio y cretinismo. Si bien en zonas endémicas en 

algunos de esos casos se ha estimado la exposición al 

cianuro en alrededor de 15-50 mg/día, debido a las 

limitaciones de los datos sobre la exposición y el efecto 

potencial de factores de confusión, como la malnutrición, el bajo contenido en proteínas de la alimentación, 

las deficiencias de vitaminas y la concentración de yodo, 

los datos disponibles no proporcionan información 

fidedigna sobre la relación dosis-respuesta para el 

cianuro. 

Los datos sobre los efectos finales distintos de la 

toxicidad aguda son algo limitados. Esto se puede 

atribuir en gran parte a las dificultades para realizar, por 

ejemplo, investigaciones de dosis repetidas o de 

toxicidad crónica debido a la elevada toxicidad aguda 

del compuesto. Los cianuros son ligeramente irritantes 
Hydrogen cyanide and cyanides: Human health aspects 

67 

de la piel y los ojos; no se han localizado datos sobre las 

propiedades de sensibilización o carcinogenicidad del 

cianuro de hidrógeno o de sus sales alcalinas. Aunque 

los datos disponibles son algo limitados, su valor 

demostrativo indica que el cianuro no es genotóxico y 

que induce efectos en el desarrollo sólo a dosis o 

concentraciones que son claramente tóxicas para las 

madres. 

Los datos disponibles sobre poblaciones humanas se 

consideran insuficientes como base para una caracterización de la relación dosis-respuesta en el caso de la 

ingestión crónica de cianuro. En un estudio de toxicidad 

con dosis repetidas de 13 semanas en el que se administró cianuro en el agua de bebida, no se detectaron 

signos clínicos asociados con efectos en el sistema 

nervioso central ni efectos histopatológicos en el cerebro 

o el tiroides de ratas o ratones expuestos a dosis de hasta 

12,5 mg y 26 mg de cianuro/kg de peso corporal al día, 

respectivamente. Con 12,5 mg de cianuro/kg de peso 

corporal al día, se observaron ligeros cambios en el 

tracto reproductivo de las ratas macho, que, aunque 

aparentemente no afectarían a la fecundidad de las ratas, 

probablemente son importantes para las personas. La 

concentración sin efectos adversos observados 

(NOAEL) para estos efectos fue de 4,5 mg/kg de peso 

corporal al día. El examen de la neurotoxicidad en este 

estudio se limitó a la observación clínica y la microscopía óptica en la autopsia. Los escasos estudios 

disponibles orientados específicamente a investigar la 

neurotoxicidad, si bien informaban de efectos adversos 

con niveles de exposición de 1,2 mg de cianuro/kg de 

peso corporal al día en ratas y de 0,48 mg de cianuro/kg 

de peso corporal al día en cabras, tienen deficiencias que 

impiden realizar su evaluación cuantitativa. 

En tres estudios separados con ratas relativos a la 

caracterización de la relación concentración-respuesta 

para la toxicidad de dosis repetidas por inhalación 

(importante en particular para el entorno ocupacional), 

no se observaron efectos sistémicos adversos en las ratas 

expuestas a cianohidrina de acetona, que se hidroliza con 

rapidez a pH fisiológico para formar cianuro de hidrógeno, en concentraciones de hasta 211 mg/m3

 (equivalentes a una concentración de 67 mg de cianuro de 

hidrógeno/m3

). La pendiente de la curva de la relación 

dosis-respuesta se explica por la observación de una 

mortalidad del 30% entre las ratas expuestas durante una 

parte del día a 225 mg de cianohidrina de acetona/m3

(71 mg de cianuro de hidrógeno/m3

). 

Es poco probable la aparición de efectos adversos 

por la exposición a las bajas concentraciones de cianuro 

que normalmente se dan en el medio ambiente 

(<1 μg/m3

 en el aire exterior; <10 μg/l en el agua). Se 

pueden producir intoxicaciones agudas por cianuro 

comiendo almendras de albaricoque, cerezas de Virginia 

y almendras de otros frutos con concentraciones 

elevadas de glucósidos cianogénicos. La yuca preparada 

de manera inadecuada puede ser peligrosa cuando 

constituye la parte más importante de la alimentación.
THE CONCISE INTERNATIONAL CHEMICAL ASSESSMENT DOCUMENT SERIES

 

 

Acrolein (No. 43, 2002)

Acrylonitrile (No. 39, 2002) 

Arsine: Human health aspects (No. 47, 2002) 

Asphalt (bitumen) (No. 59, 2004) 

Azodicarbonamide (No. 16, 1999) 

Barium and barium compounds (No. 33, 2001) 

Benzoic acid and sodium benzoate (No. 26, 2000) 

Benzyl butyl phthalate (No. 17, 1999) 

Beryllium and beryllium compounds (No. 32, 2001) 

Biphenyl (No. 6, 1999) 

Bromoethane (No. 42, 2002) 

1,3-Butadiene: Human health aspects (No. 30, 2001) 

2-Butoxyethanol (No. 10, 1998) 

Carbon disulfide (No. 46, 2002) 

Chloral hydrate (No. 25, 2000) 

Chlorinated naphthalenes (No. 34, 2001) 

Chlorine dioxide (No. 37, 2001) 

4-Chloroaniline (No. 48, 2003) 

Chlorobenzenes other than hexachlorobenzene: environmental aspects (No. 60, 2004) 

Chloroform (No. 58, 2004) 

Crystalline silica, Quartz (No. 24, 2000) 

Cumene (No. 18, 1999) 

1,2-Diaminoethane (No. 15, 1999) 

3,3'-Dichlorobenzidine (No. 2, 1998) 

1,2-Dichloroethane (No. 1, 1998) 

1,1-Dichloroethene (Vinylidene chloride) (No. 51, 2003) 

2,2-Dichloro-1,1,1-trifluoroethane (HCFC-123) (No. 23, 2000) 

Diethylene glycol dimethyl ether (No. 41, 2002)

Diethyl phthalate (No. 52, 2003) 

N,N-Dimethylformamide (No. 31, 2001) 

Diphenylmethane diisocyanate (MDI) (No. 27, 2000) 

Elemental mercury and inorganic mercury compounds: human health aspects (No. 50, 2003) 

Ethylenediamine (No. 15, 1999) 

Ethylene glycol: environmental aspects (No. 22, 2000) 

Ethylene glycol: human health aspects (No. 45, 2002) 

Ethylene oxide (No. 54, 2003) 

Formaldehyde (No. 40, 2002) 

2-Furaldehyde (No. 21, 2000) 

Glyoxal (No. 57, 2004) 

HCFC-123 (No. 23, 2000) 

Hydrogen sulfide: human health aspects (No. 53, 2003) 

Limonene (No. 5, 1998) 

Manganese and its compounds (No. 12, 1999) 

Methyl and ethyl cyanoacrylates (No. 36, 2001) 

Methyl chloride (No. 28, 2000) 

Methyl methacrylate (No. 4, 1998) 

N-Methyl-2-pyrrolidone (No. 35, 2001) 

(continued on back cover) 
THE CONCISE INTERNATIONAL CHEMICAL ASSESSMENT DOCUMENT SERIES

(continued) 

Mononitrophenols (No. 20, 2000) 

N-Nitrosodimethylamine (No. 38, 2001) 

Phenylhydrazine (No. 19, 2000) 

N-Phenyl-1-naphthylamine (No. 9, 1998) 

Polychlorinated biphenyls: human health aspects (No. 55, 2003) 

Silver and silver compounds: environmental aspects (No. 44, 2002) 

1,1,2,2-Tetrachloroethane (No. 3, 1998) 

1,1,1,2-Tetrafluoroethane (No. 11, 1998) 

Thiourea (No. 49, 2003) 

o-Toluidine (No. 7, 1998) 

Tributyltin oxide (No. 14, 1999) 

Trichloropropane (No. 56, 2003) 

Triglycidyl isocyanurate (No. 8, 1998) 

Triphenyltin compounds (No. 13, 1999) 

Vanadium pentoxide and other inorganic vanadium compounds (No. 29, 2001) 

 

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