DIAZINON = DIMPYLATE: Safety Summary for Veterinary Use

WHO Acute Hazard classification: Class II, moderately hazardous.


Mechanism of action of Diazinon

As all organophosphate insecticides, diazinon 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 Diazinon

  • LD50 acute, rats, p.o. 1250 mg/kg
  • LD50 acute, rats, dermal >2150 mg/kg
  • LD50 acute, dogs, p.o. >300 mg/kg
  • Lethal dose adult cattle, p.o. 10-25 mg/kg
  • Lethal dose calves, p.o. 0.5-1 mg/kg; toxic dose: p.o. 10 mg/kg
  • Lethal dose adult sheep, p.o. 20-30 mg/kg
  • Lethal dose adult pigs, p.o. 100 mg/kg
  • Lethal dose adult turkey, p.o. 2 mg/kg
  • Lethal dose adult chicken, p.o. 50 mg/kg; toxic dose: >10 mg/kg
  • As a general rule, dogs tolerate topically applied diazinon (shampoos, soaps, sprays, lotions, dusts, baths, collars, etc.)
  • are more sensitive to diazinon, particularly Persian cats.
  • Cattle, sheep, goats and swine also tolerate topically administered diazinon very well (sprays, dips, ear-tags, etc.).
  • Weak or stressed animals are more susceptible. Certain dog breeds (e.g. greyhounds) and geese are also more susceptible to diazinon.

Toxic Symptoms caused by Diazinon

  • 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 diazinon 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 m,iscles 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).

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

  • After slight overdose the following effects have been reported: salivation (drooling), stiff walking, vomit and depression.
  • Diazinon-impregnated collars for dogs and cats can cause local skin irritation.
  • In case of large skin injuries topical treatment with diazinon can lead to excessive cutaneous absorption with development of paraysmpathetic symptoms.
  • Organophosphates must not be administered together with other acetylcholinesterase inhibitors such as carbamates, levamisole, morantelpyrantel and neostigmine.
  • Certain solvents in the formulation can enhance the toxicity of diazinon because they accelerate its cutaneous or mucosal absorption.
  • Depolarising muscle relaxants must not be administered within 10 days following organophosphate administration because they enhance the side effects.
  • Diazinon must not be administered together with neuroleptic drugs such as phenotiazines.

Antidote and Treatment of Diazinon 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.
    • Recommended atropine dosing (one third i.v. the rest s.c.), or otherwise at the physician's discretion:
      • Cattle; 0.6 mg/kg
      • Sheep: 1.0 mg/kg
      • Horses: 0.1 mg/kg
      • Dogs: 0.3 mg/kg
      • Cats: 0.3 mg/kg
    • 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 Diazinon

  • Percutaneous absorption (i.e. through the skin) of topically administered diazinon depends on the animal species, the administered dose, and the extension of the treated body surface. As a general rule, only a relatively low amount is absorbed into blood after topical administration. Animals treated topically can ingest diazinon through licking and grooming.
  • Ingested diazinon is vastly absorbed into blood and quickly metabolized. Half-life of ingested diazinon is about 12 hours. In dogs 58% is excreted through urine in the first 24 hours after administration, >85% in the form of various metabolites.
  • One of the main metabolites, diazoxon is an acetylcholinesterase inhibitor substantially more potent (i.e. more toxic) than diazinon itself.

Environmental Toxicity of Diazinon

  • Diazinon is highly toxic to birds, fish and bees.
  • Diazinon is not very persistent in the environment. Half-life is 2 to 4 weeks
  • Diazinon does not penetrate into soil more than 2-3 cm, but there are reports on groundwater contamination with diazinon.
  • Break down of diazinon in water is much faster at low pH (half-life ~12 days) than at neutral pH (half-life ~6 months).
  • Correctly used on livestock and pets diazinon 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.

  • Diazinon belongs to the chemical class of the organophosphates.
  • Diazinon is not used in human medicines.
  • Diazinon is used in crop pesticides.
  • Diazinon 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 diazinon.

Emulsifiable concentrates (so-called ECs) as those used for spraying and dipping livestock can become extremely toxic if incorrectly stored (or manufactured!). The reason is that diazinon can break down to much more toxic pyrophosphates. This happens mainly when traces of water contaminate the original product: e.g. if open containers are stored too long and/or in wrong conditions, or if materials used for the containers are not absolutely waterproof, etc. Pyrophosphates are not built in the presence of excessive water (e.g. in plunge dips or spray races). But if pyrophosphates appear in an unduly stored product, and this product is used for dipping or spraying, the wash can be extremely toxic to livestock (and other mammals!), particularly to cattle. Back in the 60s-70s thousands of cattle and sheep died due to this problem, until formulations with stabilizers (e.g. epoxidized soybean oil) were introduced that prevented such water contaminations.

WARNING

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.

All information in this site is made available in good faith and following a reasonable effort to ensure its correctness and actuality. Nevertheless, no this regarding guarantee is given, and any liability on its accuracy, integrity, sufficiency, actuality and opportunity is denied. Liability is also denied for any possible damage or harm to persons, animals or any other goods that could follow the transmission or use of the information, data or recommendations in this site by any site visitor or third parties.

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