WHO Acute Hazard classification: Class II, moderately hazardous.

Mechanism of action of Chlorpyrifos

As all organophosphate insecticides, chlorpyrifos acts on the nervous system of the parasites (but also of mammals, birds, fish and many organisms!) as inhibitor of acetylcholinesterase (also known as AchE), an enzyme that hydrolyzes acetylcholine (Ach). Ach is a molecule involved in the transmission of nervous signals from nerves to muscles (so-called neuromuscular junctions) and between neurons in the brain (so-called cholinergic brain synapses).

AchE's role is to terminate the transmission of nervous signals where Ach is the neurotransmitter (there are several other neurotrasmitters). By inhibiting the activity of AchE, carbamates prevent the termination of those nervous signals, i.e. the neurons remain in constant activity and excitation, massively disturbing the normal movements of the parasites. The bottom line for the parasites is that they are paralyzed and die more or less quickly. Organophosphates bind irreversibly to AchE, in contrast with carbamates, another chemical class of parasiticides, which bind reversibly to AchE.>

Acute Toxicity and Tolerance of Chlorpyrifos

  • LD50 acute, rats, p.o. 95 to 270 mg/kg
  • LD50 acute, mice, p.o. 60 mg/kg
  • LD50 acute, rabbits, p.o. 1000 mg/kg
  • LD50 acute, rats, dermal >2000 mg/kg
  • LD50 acute, chicken, p.o. 32 mg/kg
  • LD50 acute, pheasant, p.o. 8.4 mg/kg
  • LD50 acute, sheep, p.o. 800 mg/kg
  • Certain dog breeds (e.g. greyhounds, whippets), cats and certain birds (e.g. geese) and are also more susceptible to chlorpyrifos.
  • Weak or stressed animals are more susceptible.

Toxic Symptoms caused by Chlorpyrifos

  • Toxic symptoms caused by organophosphate intoxications are the same as those of carbamates intoxication, but are usually more severe and recovery is slower because organophosphates bind irreversibly to acetylcholinesterase, whereas carbamate binding is reversible.
  • Acute intoxication. Is caused by inhibition of the acetylcholinesterase: as a consequence acetylcholine accumulates in the neuromuscular synapses (including those in skeletal, smooth and cardiac muscles), in the neuroglandular connections, and in the CNS (Central Nervous System). This causes hyperexcitation in all the muscarinic and nicotinic cholinergic receptors, which disturbs the normal functioning of the affected organs.
  • After accidental ingestion or massive dermal overdose, intoxication follows an acute development. Ingested chlorpyrifos is vastly and quickly absorbed into blood. The symptoms appear a few minutes to 2 hours after ingestion, often dramatically. If the patient survives the first 24-48 hours, prognosis is favorable.
  • Usually muscarinic symptoms are the first to manifest, followed by hyperexcitation of the nicotinic receptors of vegetative ganglions and motor end plates. If the intoxication crosses the blood-brain barrier the CNS becomes hyperexcited as well.
  • Main muscarinic symptoms:
    • Exocrine glands: salivation (drooling), lacrimation (excessive secretion of tears), sudoration (excessive sweating).
    • Eyes: miosis (constriction of the pupil), in swine nystagmus (uncontrolled eye movements).
    • Digestive system: nausea, vomit (particularly in dogs), diarrhea, tenesmus (need for imperative defecation), fecal incontinence.
    • Cardiovascular system: bradycardia (low heart rate), low blood pressure.
    • Respiratory system: bronchoconstriction, bronchospasms, cough, tachypnea (low breathing rate), dispnea (shortness of breath).
    • Urinary system: frequent urination.
  • Main nicotinic symptoms
    • Muscles: anxiety followed by depression, trembling, ataxia (uncoordinated movements), muscular stiffness, generalized muscular spasms, paralysis.
  • Main CNS symptoms:
    • Lethargy, fatigue, trembling, spasms and coma with respiratory paralysis. Death is mostly a consequence of paralysis of the respiratory muscles, of the inhibition of the respiratory center and of excessive bronchial constriction and secretion. In swine death can follow within 15 to 30 minutes after exposure to the lethal dose.
  • Chronic intoxication. In addition to the acute intoxication, some organophosphates can have a delayed neurotoxic effect (so called OPIDN = organophosphorous ester-induced delayed neuropathy), which develops 7 to 21 days after exposure to the toxic dose and appears as weakness, ataxia (uncoordinated movements), proprioceptive dysfunctions (disturbed awareness of posture and movements), particularly of the hind legs, and paralysis. It is due to degeneration of the axons (nerve fibers) of central and peripheral nerve cells, which is species-specific. Depending on which particular organophosphate caused the intoxication, OPIDN is irreversible or allows a slow recovery after several weeks.
  • Organophosphate-induced Intermediate Syndrome (IMS) is another possible clinical development observed mainly in dogs and cats (and humans) after massive overdosing with certain organophosphates, including e.g. diazinon, chlorpyrifos, fenthion, malathionphosmet and trichlorfon. Clinical symptoms include acute paralysis and weakness in several muscles (e.g. neck flexors, proximal limbs, etc.), including respiratory muscles 1 to 4 days after intoxication. Other symptoms include weakness, depression, ptosis (drooping or falling of the lower of upper eyelids), double vision (diplopia), disturbed deep tendon reflexes. These symptoms may last for a few days or several weeks, depending on the compound involved and the dose.
  • DIAGNOSIS. An important diagnostic parameter is the global acetylcholinesterase (AchE) activity in blood. A drop below 25% of the normal value indicates intoxication with an AchE inhibitor (not necessarily an organophosphate or carbamate pesticide).

Chlorpyrifos Side Effects, Adverse Drug Reactions (ADRs) and Warnings

  • After slight overdose the following effects have been reported: salivation (drooling), soft feces, frequent urination and defecation, etc.
  • Chlorpyrifos-impregnated collars for dogs and cats can cause local skin irritation.
  • Young animals must be treated with utmost care.
  • Chlorpyrifos should not be administered to pregnant dams during the last third of pregnancy.
  • Chlorpyrifos should not be administered to animals suffering diarrhea, chronic constipation, colic, convulsions, respiratory, renal and/or cardiac disturbances.
  • In case of large skin injuries topical treatment with chlorpyrifos can lead to excessive cutaneous absorption with development of paraysmpathetic symptoms.
  • Certain solvents in the formulation can enhance the toxicity of chlorpyrifos because they accelerate its cutaneous or mucosal absorption.
  • Organophosphates must not be administered together with other acetylcholinesterase inhibitors such as carbamates, levamisole, morantelpyrantel and neostigmine.
  • Depolarising muscle relaxants must not be administered within 10 days following organophosphate administration because they enhance the side effects.>
  • Chlorpyrifos must not be administered together with neuroleptic drugs such as phenotiazines.

Antidote and Treatment of Chlorpyrifos Intoxication

  • Atropine (a parasympatholytic drug) is the antidote for the acute muscarinic symptoms, the most dangerous ones. It is an antagonist of acetylcholine in the muscarinic receptors of the nervous system.
    • Cattle; 0.6 mg/kg
    • Sheep: 1.0 mg/kg
    • Horses: 0.1 mg/kg
    • Dogs: 0.3 mg/kg
    • Recommended atropine dosing (one third i.v. the rest s.c.), or otherwise at the physician's discretion:
    • Atropinization efficacy peaks when the pupils dilate and salivation stops. If necessary treatment can be repeated every 4 to 6 hours up to a max. dose of 6 mg/kg.
  • Causal antidotes that act upon the toxic mechanisms can also be used. Pralidoxime (2 to 5 mg/kg i.v.; maybe i.m.) and obidoxime (20 to 100 mg/kg) can reactivate the cholinesterase but not later than 24 hours after ingestion, and treatment should not be repeated more than once or twice. Both should be administered after atropine. Re-treatment not earlier than 20 minutes, usually after 2 hours. WARNING: obidoxime can also act as a cholinesterase inhibitor!
  • Symptomatic and support measures may be advisable:
    • Breathing support: artificial respiration, aspiration of bronchial secretions, oxygen support
    • After oral poisoning: induced vomit (not later than 2 hours after ingestion; contraindicated if the patient is depressed) or stomach lavage, administration of active charcoal or mineral oil.
    • After dermal poisoning: rinse the injury with abundant water with alkaline detergent, but without scratching or scrubbing.
    • Treatment of acidosis and spasms.
    • Administration of electrolytes and multivitamins to support the hepatic metabolism.

Pharmacokinetics of Chlorpyrifos

  • Percutaneous absorption (i.e. through the skin) of topically administered chlorpyrifos depends on the animal species, the administered dose, and the extension of the treated body surface. Animals treated topically can ingest chlorpyrifos through licking and grooming.
  • Orally administered chlorpyrifos is partly excreted unchanged through the feces. Once absorbed into blood it is quickly metabolized in the liver and rapidly excreted through urine. Excretion half-life is about 2 to 3 days. Administered as a spray to cows it was detected in their milk for 4 days following treatment.

Environmental Toxicity of Chlorpyrifos

  • Chlorpyrifos is highly toxic to certain bird species (e.g. house sparrow, red-winged blackbird, Japanese quail, ring-necked pheasant, common pigeon and mallard duck) but not to other species (e.g. bobwhite quail).
  • Chlorpyrifos is highly toxic to fish and aquatic invertebrates. Toxicity increases significantly with temperature.
  • Chlorpyrifos tend to bioaccumulate significantly in the aquatic food chain.
  • Chlorpyrifos is moderately persistent in the soil. Half-life ranges from 2 weeks to 1 year, depending on temperature, soil type, pH, etc. It is less persistent in sandy than in clay soils, and in acid than in alkaline soils.
  • Chlorpyrifos binds strongly to soil particles and is poorly soluble in water. For these reasons it tends to accumulate in soils.
  • Due to its poor motility in soil groundwater contamination is unlikely to occur.
  • In aquatic environments dissipation is mainly due to volatilization (half-life 3 to 20 days). Hydrolysis is slow and strongly depending on temperature. Photo-hydrolysis half-life is 3 to 4 weeks. Hiogh temperature and alkaline pH accelerate degradation.
  • Correctly used on livestock and pets chlorpyrifos is unlikely to be detrimental for the environment, provided that disposal of old dip wash, product waste and used containers is done according to the label recommendations.

Additional information

Click here for a list and overview of all safety summaries of antiparasitic active ingredients in this site.

  • Chlorpyrifos belongs to the chemical class of the organophosphates.
  • Chlorpyrifos is not used in human medicines.
  • Chlorpyrifos is used in crop pesticides.
  • Chlorpyrifos is used in public or domestic hygiene as a biocide.
  • Click here for General safety of antiparasitics for domestic animals.
  • Click here for General safety of antiparasitics for humans.
  • Click here for General safety of antiparasitics for the environment.
  • Click here for technical and commercial information on chlorpyrifos.


If you intend to use a veterinary drug containing this active ingredient you must carefully read and follow the safety instructions in the product label.  Always ask your veterinary doctor, or pharmacist, or contact the manufacturer. Be aware that the safety instructions for the same veterinary medicine may vary from country to country.

The information in this page must not be confused with the Materials and Safety Datasheets (MSDS) officially issued by manufacturers for active ingredients and many other chemicals. MSDSs target safety during manufacturing, transport, storage and handling of such materials. This safety summary is a complement to the information on product labels and MSDS.

The toxicity of an active ingredient must not be confused with the toxicity of finished products, in this case parasiticidal drugs or pesticides. Finished products contain one or more active ingredients, but also other ingredients that can be relevant from the safety point of view.

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