PROFESSIONAL VERSION

Cyanide Poisoning in Animals

By Rhian B. Cope, BVSc, BSc, PhD, DABT, DABVT, FACTRA, Australian Pesticides and Veterinary Medicines
Authority, Australian Government
Reviewed/Revised Apr 2021 | Modified Sept 2024

Etiology | Clinical Findings | Diagnosis | Treatment, Control, and Prevention |

Key Points | For More Information
Cyanide poisoning results from exposure to a source of cyanide ions (CN-). There are four main
syndromes in animals:

Classical acute cyanide poisoning is when CN- binds to, and inhibits, the ferric (Fe3+) heme
moeity form of mitochondrial cytochrome c oxidase (synonyms: aa3, complex IV,
cytochrome A3, EC 1.9.3.1). This blocks the fourth step in the mitochondrial electron
transport chain (reduction of O2 to H2O), resulting in the arrest of aerobic metabolism,
systemic hypoxia, and death from histotoxic anoxia. Tissues that heavily depend on
aerobic metabolism such as the heart and brain are particularly susceptible to these
effects. Cyanide also binds to other heme-containing enzymes, such as members of the
cytochrome p450 family, and to myoglobin. However, these tissue cyanide "sinks" do not
provide sufficient protection from histotoxic anoxia. The acute lethal dosage of hydrogen
cyanide (HCN) in most animal species is ~2 mg/kg. Plant materials containing ≥200 ppm of
cyanogenic glycosides are dangerous. Cyanide poisoning is often a component of smoke
inhalation poisoning.
Chronic cyanide poisoning-related hypothyroidism is due to disruption of iodide uptake by
the follicular thyroid cell sodium-iodide symporter by thiocyanate, a metabolite in the
detoxification of cyanide.
Chronic cyanide and cyanide metabolite (eg, various glutamyl beta-cyanoalanines)-
associated neuropathy toxidromes, which include diseases such as sorghum cystitis ataxia
syndrome in horses, as well as various cystitis ataxia syndromes in cattle, sheep, and goats
Chronic cyanogenic glycoside exposure (notably from Sorghum spp) -associated
musculoskeletal teratogenesis (ankyloses or arthrogryposes) and abortion
Although cyanide levels can be determined in various biological media from poisoned animals, often
the most reliable method of diagnosis is determination of cyanide (and/or cyanide glycoside and/or
relevant cyanide metabolite) concentrations in food and stomach contents. Feed analysis and
neurohistopathology are the gold-standard method of diagnosis of cyanide-associated neuropathy
toxidromes. Likewise, feed analysis and fetal pathology are the gold-standard methods of diagnosis of
chronic cyanogenic glycoside-associated teratogenic syndromes.

Etiology of Cyanide Poisoning in Animals

Various chemical forms of cyanides are found in plants, fumigants, soil sterilizers, fertilizers (eg,
cyanamide), pesticides/rodenticides (eg, calcium cyanomide), and salts used in industrial processes,
such as gold mining, metal cleaning and electroplating, photographic processes, and others. Hydrogen
cyanide is also known as prussic acid, and cyanide salts liberate cyanide gas in the presence of acids
(eg, in the stomach).

Cyanide preparations are still used as control agents for vertebrate pests, such as feral pigs, fox,
Australian brush-tailed possums, and other pest or predator species in a number of countries.

Cyanide salts are still used as killing agents in entomology and (illegally) as a method of fishing and/or
collection of aquarium fish species (ie, cyanide fishing). Various nitriles can be metabolized in such a
way that cyanide is released.

Combustion of common polyacrylonitriles (plastics), wool, silk, keratin, polyurethane

(insulation/upholstery), melamine resins (household goods), and synthetic rubber results in the release
of cyanide gas.

Car fires are notorious sources of cyanide exposure, and cyanide is also a notable component of
internal combustion engine exhaust and tobacco smoke. Cyanide poisoning is thus a common
component of smoke inhalation toxidromes.

Toxicity can result from accidental, improper, or malicious use or exposure. However, in livestock
species, the most frequent cause of acute and chronic cyanide poisoning is ingestion of plants that
either constitutively contain cyanogenic glycosides or are induced to produce cyanogenic glycosides
and cyanolipids as a protective response to environmental conditions (plant cyanogenesis). Plant
cyanogenesis is a common process and has been documented in >3,000 different plant species
distributed over ~110 different families of ferns, gymnosperms, and angiosperms. Of these plants,
~300 species are potential causes of acute and chronic cyanogenic glycoside poisoning, and there are
~75 different cyanogenic glycosides (all of which are O-beta-glycosidic derivatives of alpha-
hydroxynitriles).

Plant species of notable veterinary importance include Sorghum spp (Johnson grass, Sudan grass, and S
bicolor, the common cereal grain crop referred to as "sorghum" or the synonyms durra, jowari, milo),
Acacia greggii (guajillo), Amelanchier alnifolia (western service berry), Linum spp (linseeds and flaxes),
Sambucus nigra (elderberry), Suckley suckleyana (poison suckleya), Triglochin maritima and T palustris
(marsh arrow grasses), Mannihot esculentum (cassava), all members of the Prunus genus until proved
otherwise (apricot, peach, chokecherry, pincherry, wild black cherry, ornamental cherry, peaches,
nectarines, apricots, almonds, bird cherries, black thorn, cherry laurels [commercial orchard species
are often specifically bred for low cyanide content; however, ornamental members of this genus are
often highly poisonous]), Nandina domestica (heavenly or sacred bamboo), Phaseolus lunatus (lima
beans), members of the Vicia genus until proved otherwise (vetches; often, pasture species have been
bred for low cyanogenesis), Lotus spp (bird's-foot treefoils; often, pasture species have been bred for
low cyanogenesis), Trifolium sp (clovers; often, pasture species have been bred for low cyanide content),
Zea mays (corn), Eucalyptus spp (gum trees), Hydrangea spp (hydrangeas), Pteridium aquilinum (bracken
fern), Bahia oppositifolia (bahia), and Chaenomales spp (flowering quince).
A number of insect species are also able to synthesize hydrogen cyanide and/or sequester hydrogen
cyanide that is derived from the cyanogenic glycosides of their plant hosts (notably the USA eastern
tent caterpillar Malacosoma americanum that is associated with mare reproductive loss syndrome;
however, cyanide is not the cause of mare reproductive loss syndrome. Invertebrates such as Burnet
moths (Zygaena spp) that feed on bird's-foot trefoils), as well as certain centipede and millipedes, are
potentially hazardous food sources for exotic pet species.

Plant cyanogenesis in response to environmental stressors is an important part of the etiology and risk
of acute cyanogenic glycoside poisoning. Within plants, amino acids that are not used for protein
synthesis can be metabolized to alpha-hydroxynitriles and then to cyanogenic glycosides. Plants are
protected from the potential adverse effects of cyanogenic glycosides by two features: cyanogenic
glycosides are largely found within cell vacuoles, and the presence of the detoxifying enzyme beta-
cyanoalanine synthase (which is responsible for production of some of the cyanide derivatives
putatively involved in the chronic cyanide-associated neurologic toxidromes). Even so-called
"acyanogenic" plants can become toxic under appropriate environmental circumstances.

Environmental conditions that damage relevant plant species, reduce protein synthesis, enhance the
conversion of nitrate to amino acids in the presence of reduced protein synthesis, and/or inhibit beta-
cyanoalanine synthase potentially increase the risk of cyanogenesis. Relevant environmental factors
include crushing, wilting, freezing, high environmental temperatures, herbicide treatment, water stress,
cool and moist growing conditions, nitrate fertilization, high soil nitrogen:phosphorus ratios, soil
phosphorus deficiency, low soil sulfur (decreases detoxification of cyanogenic glycosides to
thiocyanates within plants), insect attack, and various plant diseases. Herbicide treatment of plants is
important in that it may also increase plant palatability.

Crushing and/or mastication of potentially cyanogenic plants is important in development of the acute
toxidrome, because this releases cyanogenic glycosides from plant cell vacuoles and exposes them to
catabolism by beta-glucosidase and hydroxynitrile lyase present in the plant cell cytosol.

Young, rapidly growing areas of plants and areas of regrowth after cutting often have high cyanogenic
glycoside content. As a rough approximation, rapidly growing Sorghum spp are often hazardous until
they reach ~60 cm in height; however, this is no guarantee of safety, and if there is any doubt regarding
cyanogenic potential, samples of potential forage should be tested. Plant seeds and leaves typically
have higher cyanogenic potential, whereas the fleshy parts of fruits generally have low levels. Drying
often increases the cyanogenic potential of plants, whereas ensiling may reduce cyanide content by
~50%.

Beta-glucosidase and hydroxynitrile lyase are also present in the rumen microflora, and a rumen pH of
~6.5–7 favors conversion of cyanogenic glycosides to cyanide. Ruminants on high-energy grain rations
are somewhat less susceptible, because their lower rumen pH (~4–6) reduces the formation of cyanide.
Consumption of water before grazing on cyanogenic pastures appears to increase the risk.
Monogastric animals with low stomach pH are also somewhat less susceptible to cyanogenic glycoside
poisoning. However, these factors do not guarantee immunity from poisoning.

Under conditions of low-level exposure, mammals detoxify ~80% of ingested cyanide to thiocyanate via
mitochondrial rhodanese. Thiocyanate is then largely excreted in urine. Often, the rate of the
rhodanese pathway is limited by the availability of thiosulfate; also notably, dogs have lower overall
rhodanese activity than other species. Minor, but toxicologically important, pathways of detoxification
in mammals include the combination of cyanide with hydroxycobalamin (vitamin B12a) to yield
cyanocobalamin (vitamin B12), and the nonenzymatic combination of cyanide with cysteine to form
beta-thiocyanoalanine, which is converted to 2-iminothiazolidine-4-carboxylic acid and subsequently
excreted. Small amounts of beta-thiocyanoalanine are also excreted in saliva. Dietary levels of sulfur
amino acids (L-cysteine and L-methionine) strongly influence the rate of detoxification of cyanide, and
low dietary intakes are associated with higher blood cyanide levels, particularly under conditions of
chronic, low level exposure. Dietary sulfur and sulfur amino acid intake are known to strongly affect the
neurologic toxidromes associated with chronic cyanide/cyanogenic glycoside exposure in people.

Chronic low-level cyanide/cyanogenic glycoside exposure is associated with increased exposure to the
cyanide metabolite thiocyanate. Under conditions of thiocyanate overload, thiocyanate acts as a
competitive inhibitor of thyroid follicular cell iodine uptake by the sodium/iodide symporter. This
results in reduced iodination of tyrosine, reduced T3 synthesis, increased blood TSH, goiter, and
hypothyroidism. Similar effects occur with some plant glucosinolates (goitrogenic glycosides). Selenium
deficiency appears to enhance these effects.

Chronic, low-level cyanide/cyanogenic glycoside exposure (often in combination with low dietary sulfur
and/or sulfur amino acid intake) is associated with neuropathy syndromes in horses and ruminants.
Sorghum cystitis ataxia syndrome of horses is associated with diffuse nerve fiber degeneration in the
lateral and ventral funiculi of the spinal cord and brain stem. Similar syndromes have been described in
ruminants. Comparisons between these syndromes as chronic cyanogenic glycoside–associated human
myeloneuropathies (such as Konzo and tropical ataxic neuropathy) have been made; however, the
precise toxins and modes of action are yet to be fully defined. All of these toxidromes appear to be
related to a combination of chronic cyanide/cyanogenic glycoside exposure combined with low dietary
sulfur and/or sulfur amino acid intake and possibly other nutritional deficiencies. Lathyrogenic plant
cyanide metabolites such as beta-cyanoalanine have been implicated as causative or at least
contributory agents.

Chronic, low-level cyanogenic glycoside exposure (notably from Sorghum spp) has been associated with
musculoskeletal teratogenesis (ankyloses or arthrogryposes) and abortion.

Clinical Findings of Cyanide Poisoning in Animals

Acute cyanide poisoning: Signs generally occur within 15–20 minutes to a few hours after animals
consume toxic forage, and survival after onset of clinical signs is rarely >2 hours. Excitement can be
displayed initially, accompanied by rapid respiration rate. Dyspnea follows shortly, with tachycardia.
The classic "bitter almond" breath smell may be present; however, the ability to detect this smell is
genetically determined in people, and anosmic people (a significant proportion of the population)
cannot detect it. Salivation, excess lacrimation, and voiding of urine and feces may occur. Vomiting may
occur, especially in pigs. Muscle fasciculation is common and progresses to generalized spasms and
coma before death. Animals may stagger and struggle before collapse. In other cases, sudden
unexpected death may ensue. Mucous membranes are bright red but may become cyanotic terminally.
Venous blood is classically described as "cherry red" because of the presence of high venous blood
pO2; however, this color rapidly changes after death. Serum ammonia and neutral and aromatic amino
acids are typically increased. Cardiac arrhythmias are common due to myocardial histotoxic hypoxia.
Death occurs during severe asphyxial convulsions. The heart may continue to beat for several minutes
after struggling, and breathing stops. The elimination half-life of cyanide in dogs is reported to be 19
hours, so prognosis of recovery without therapeutic intervention is grave: it would take more than
4 days to eliminate >95% of the cyanide present.

Chronic cyanide poisoning: Chronic cyanogenic glycoside hypothyroidism will present as hypothyroidism
with or without goiter. Cystitis ataxia toxidromes are typically associated with posterior ataxia or
incoordination that may progress to irreversible flaccid paralysis, cystitis secondary to urinary
incontinence, and hindlimb urine scalding and alopecia. Death, although uncommon, is often
associated with pyelonephritis. Late-term abortion and musculoskeletal teratogenesis may also occur.

Lesions
Acute cyanide poisoning: Necropsy personnel may require appropriate personal protective equipment,
including respirators with suitable cartridges. Venous blood is classically described as being "bright
cherry red"; however, this color rapidly fades after death or if the blood is exposed to the atmosphere.
Whole blood clotting may be slow or not occur. Mucous membranes may also be pink initially, then
become cyanotic after respiration ceases. The rumen may be distended with gas; in some cases the
odor of “bitter almonds” may be detected after opening. Rumen contents may provide a positive
sodium picrate paper test (or positive results on other rapid cyanide test strip systems). Rumen gases
may provide positive results in cyanide Draeger tube rapid test systems. Agonal hemorrhages of the
heart may be seen. Liver, serosal surfaces, tracheal mucosa, and lungs may be congested or
hemorrhagic; some froth may be seen in respiratory passages. Cyanide also binds to iron (both Fe2+
and Fe3+) present in myoglobin (although this occurs more slowly than the binding to cytochrome c
oxidase and, hence, is not protective); this may result in a generalized dark coloration of skeletal
muscle. Neither gross nor histologic lesions are consistently seen.

Multiple foci of degeneration or necrosis may be seen in the CNS of dogs chronically exposed to
sublethal amounts of cyanide. These lesions have not been reported in livestock.

Chronic cyanide poisoning: Goiter may be present. Cystitis ataxia toxidromes are characterized by
opportunistic bacterial cystitis with or without pyelonephritis and diffuse nerve fiber degeneration in
the lateral and ventral funiculi of the spinal cord and brain stem. Hindlimb urine scalding and alopecia
may be present.

Diagnosis of Cyanide Poisoning in Animals

Determination of cyanide (and/or cyanide glycoside and/or relevant cyanide metabolite)
concentrations in food and stomach contents
For cyanide-associated neuropathy syndromes: feed analysis and neurohistopathology
For chronic cyanogenic glycoside-associated teratogenic syndromes, Feed analysis and
fetal pathologies
Appropriate history, clinical signs, postmortem findings, and demonstration of HCN in rumen (stomach)
contents or other diagnostic specimens support a diagnosis of cyanide poisoning. Veterinarians should
be aware of the possible need to use appropriate personal protective equipment, including a
respirator, when collecting samples that may liberate cyanide gas (eg, rumen contents and rumen gas
cap).

A rapid qualitative and presumptive diagnosis can be made by testing representative plant samples or
stomach contents using the picric acid paper test or by collecting rumen gas cap samples by
trocarization and testing with a Draeger cyanide gas detection tube or other cyanide gas detection
system. Negative results with such rapid presumptive tests do not completely exclude the possibility of
cyanide poisoning.

Suitable specimens for more sophisticated testing include the suspected food source, rumen/stomach
contents, samples of the rumen gas cap, heparinized whole blood, liver, and muscle. Antemortem
whole blood is preferred; other specimens should be collected as soon as possible after death,
preferably within 4 hours. Specimens should be sealed in an airtight container, refrigerated or frozen,
and submitted to the laboratory without delay. When cold storage is unavailable, immersion of
specimens in 1%–3% mercuric chloride has been satisfactory. The rationale for using liver as a
diagnostic sample is that cyanide binds to the Fe3+ form of cytochrome p450 and other heme-
containing metabolic enzymes. The rationale for using skeletal muscle is that cyanide will bind to the
iron moiety in myoglobin.

Measurement of the urinary metabolite of cyanide, thiocyanate, may reveal increased concentrations
after cyanide poisoning.

Hay, green chop, silage, or growing plants containing >220 ppm cyanide as HCN on a wet-weight (as is)
basis are very dangerous as animal feed. Forage containing < 100 ppm HCN, wet weight, is usually safe
to pasture. Analyses performed on a dry-weight basis have the following criteria: >750 ppm HCN is
hazardous, 500–750 ppm HCN is suspect, and < 500 ppm HCN is considered safe.

Normally expected cyanide concentrations in blood of most animal species are usually < 0.5 mcg/mL.
Minimal lethal blood concentrations are ~3 mcg/mL or less. Cyanide concentrations in muscle are
similar to those in blood, but concentrations in liver are generally lower than those in blood. In dogs,
whole blood cyanide concentrations may be 4–5 times greater than serum concentrations because of
binding to ferric ions and sequestration in RBCs.

Differential diagnoses include poisonings by:

nitrate or nitrite
urea
organophosphates
carbamates
chlorinated hydrocarbon pesticides
toxic gases (carbon monoxide and hydrogen sulfide)
as well as infectious or noninfectious diseases and other toxidromes that cause sudden
death
Treatment, Control, and Prevention of Cyanide Poisoning in
Animals
Immediate treatment with hydroxocobalamin and oxygen
Methylene blue if diagnosis is in doubt (signs are similar to those of nitrate poisoning)
Removal from the source of exposure
In cases of acute cyanide poisoning, immediate treatment is necessary. Activated charcoal is ineffective,
and its use is not recommended. Hydroxocobalamin (vitamin B12a ) is the gold-standard antidote for
cyanide because of its effectiveness and low toxicity. It has a great advantage of not further
compromising tissue oxygenation and not inducing hypotension. Hydroxocobalamin detoxifies cyanide
by binding to it and forming cyanocobalamin (ie, a decoy receptor approach), which is then excreted in
urine. The suggested dosage is 70 mg/kg, infused IV over 15 minutes, repeated as necessary.
Hydroxocobalamin produces chromaturia (which may result in false urinalysis results), as well as
infusion site reactions, GI upset, pruritus, and dysphagia. Hydroxocobalamin is costly, which may limit
its use in herd and flock animals.

When available, oxygen should be used to supplement antidotal therapy, especially in small animals.
Hyperbaric oxygen therapy (100% oxygen breathed intermittently at a pressure >1 atmosphere
absolute) causes an above-normal partial pressure of oxygen (pO2) in arterial blood and markedly
increases the amount of oxygen dissolved in plasma. Oxygen-dependent cellular metabolic processes
benefit from heightened oxygen tension in capillaries and enhanced oxygen diffusion from capillaries
to critical tissues.

The older (and less expensive—making it likely more practical for grazing animals) approach to the
treatment of acute cyanide poisoning is to break the cyanide-cytochrome c oxidase bond and
reestablish the mitochondrial electron transport chain. One way to accomplish this is by using Fe3+ in
hemoglobin (ie, inducing methemoglobinemia), which then acts as a high-affinity decoy chemical
receptor for cyanide and forms cyanmethemoglobin. Classically, various nitrites have been used for
this purpose; eg, inhaled amyl nitrite followed by IV injection of a nitrite salt (typically sodium nitrite)
has been used to rapidly induce methemoglobinemia. Cyanide bound to methemoglobin can then be
detoxified by rhodanese to thiocyanate. Because the rhodanese-mediated detoxification of cyanide to
thiocyanate is usually capacity and rate limited by the availability of sulfur donors, treatment with
nitrites is usually followed up by injection of sodium thiosulfate. Oral dosing with sodium thiosulfate
into the rumen and/or stomach has also been suggested because the reaction between thiosulfate and
cyanide can also occur nonenzymatically, and this may reduce any ongoing production of cyanide in
the rumen/stomach environments.

If possible, the contents of one 0.3-mL vial of amyl nitrite should be inhaled by the animal as soon as
possible after exposure, followed by an IV infusion of sodium nitrite (10 g/100 mL of distilled water or
isotonic saline; 20 mg/kg body weight) over 3–4 minutes. Nitrite treatment is then followed by a slow IV
injection of sodium thiosulfate (20% w/w) at ≥500 mg/kg. Thiosulfate is generally well tolerated;
however, vomiting and hypotension can occur. The thiosulfate injection can be repeated if necessary.
Oral administration of thiosulfate can also be considered in an attempt to convert any cyanide in the
stomach/rumen into thiocyanate. Sodium nitrite therapy may be carefully repeated at 10 mg/kg, every
2–4 hours or as needed. Ideally, decisions regarding repeated treatment with nitrites should consider
the degree of methemoglobinemia present.

Notably, thiosulfate treatment alone (sodium thiosulfate at ≥500 mg/kg, IV, plus 30 g/cow orally for
ruminants, with the objective of facilitating the detoxification of any remaining HCN in the rumen) has
been successful in some cases. However, thiosulfate treatment should ideally be preceded by nitrite
induction of methemoglobinemia in cases of confirmed cyanide poisoning. However, because
thiosulfate is generally well tolerated, it is often administered alone in situations when cyanide
exposure is likely but unconfirmed (eg, smoke inhalation or exposure to fires).

The best preventive step is to test suspect feed and/or pastures before allowing consumption. Pasture
and forage sorghums (eg, Sudan grass and sorghum-Sudan grass hybrids) should not be grazed until
they are >60 cm tall or have been proved by testing to have acceptable cyanide levels, to reduce danger
from prussic acid poisoning. Animals should be fed before first turning out to pasture; hungry animals
may consume forage too rapidly to detoxify HCN released in the rumen. Animals should be turned out
to new pasture later in the day; potential for prussic acid release is reported to be highest during early
morning hours. Free-choice salt and mineral with added sulfur may help protect against prussic acid
toxicity. Grazing should be monitored closely during periods of environmental stress, eg, drought or
frost. Abundant regrowth of sorghum can be dangerous; these shoots should be frozen and wilted
before grazing.

Green chop forces livestock to eat both stems and leaves, thereby reducing problems caused by
selective grazing. Cutting height can be raised to minimize inclusion of regrowth.

Sorghum hay and silage usually lose ≥50% of prussic acid content during curing and ensiling processes.
Free cyanide is released by enzyme activity and escapes as a gas. Although a rare occurrence,
hazardous concentrations of prussic acid may still remain in the final product, especially if the forage
had an extremely high cyanide content before cutting. Hay has been dried at oven temperatures for up
to 4 days with no significant loss of cyanide potential. These feeds should be analyzed before
use whenever high prussic acid concentrations are suspected. Potentially toxic feed should be diluted
or mixed with grain or forage that is low in prussic acid content to achieve safe concentrations in the
final product. At least in theory, the risk of chronic cyanide poisoning syndromes may be reduced by
iodine supplementation in the case of hypothyroidism and by sulfur-containing amino acids in the case
of chronic neurologic toxidromes. Great care must be taken when providing supplemental elemental
sulfur sources in ruminants because of the possible risk of polioencephalomalacia.

Key Points

Manage grazing and feed conditions for environmental stress to minimize risk, and
analyze feed before allowing consumption.
Hydroxocobalamin plus 100% oxygen should be administered as soon as possible
after suspected cyanide poisoning.
Treatment should not be delayed for diagnostic confirmation.
 Removal from the source of exposure is the main clinical priority in chronic cyanide-
associated toxidromes.
Prognosis for cases of chronic cyanide poisoning other than those associated with
thyroid syndromes is guarded.

For More Information

Also see pet health content regarding cyanide poisoning.

Cyanide Poisoning in Animals Cyanide Poisoning in Animals