PERMETHRIN: Safety Summary for Veterinary Use

WHO Acute Hazard classification: Class II, moderately hazardous.


Mechanism of action of Permethrin

Synthetic pyrethroids, including permethrin, have a similar mode of action as organochlorines. They act on the membrane of nerve cells blocking the closure of the ion gates of the sodium channel during re-polarization. This strongly disrupts the transmission of nervous impulses, causing spontaneous depolarization of the membranes or repetitive discharges. At low concentrations insects and other arthropods suffer from hyperactivity. At high concentrations they are paralyzed and die. Sensory and nervous cells are particularly sensitive.


Acute Toxicity and Tolerance of Permethrin

  • Toxicity of permethrin depends strongly on the cis:trans isomer ratios (usually 80:20; 40:60; 25:75), whereby the cis isomers are biologically more active but also more toxic than the trans isomers. Studies in mice suggest that oral cis-permethrin is >10x more toxic than trans-permethrin, and 2-5x more toxic than the 40:60 mixture most used in toxicity studies.
  • LD50 acute, rats, p.o. 400 mg/kg (in oil vehicle, 40:60 cis:trans mixture) to 1350 - 4000 mg/kg (in aqueous vehicle, depending on the study). The vehicle-dependant and isomer-dependent differences in the acute oral toxicity are typical for synthetic pyrethroids and some other active ingredients.
  • LD50 acute, rats, dermal, 4000 mg/kg
  • LD50 acute, cats, dermal, 100 mg/kg!
  • As a general rule, dogs, livestock (cattle, sheep, goats, swine), horses, and poultry tolerate permethrin and most synthetic pyrethroids very well, since toxicity is about 1000x higher to insects and other arthropods than to mammals. But in case of sustained skin or inhalation exposure, or after direct contact with open wounds toxicity to mammals can be higher.
  • Besides neurotoxic effects, permethrin has also hepatotoxic effects and induces microsomal enzymes in the liver.
  • WARNING: permethrin is toxic to cats! Cats do not tolerate therapeutic doses for dogs. This is associated with glucuronidase deficiency in cats, the enzyme responsible for breaking down permethrin and other synthetic pyrethroids in the organism in a process called glucuronidation. As a consequence, permethrin remains much longer in the cat's organism than in dogs or other mammals.

Toxic Symptoms caused by Permethrin Poisoning

  • The primary symptoms of intoxication with permethrin and other synthetic pyrethroids affect mainly the nervous and muscular systems.
  • Most frequent symptoms are:
    • Ataxia (uncoordinated movements)
    • Hyperreactivity (exaggerated reaction to stimuli)
    • Tremor (uncoordinated trembling or shaking movements)
    • Paresthesia (skin sensation of tingling, tickling, prickling)
    • Exhaustion (lethargy, fatigue)
    • Hypersalivation (drooling)
    • Vomit
    • Diarrhea
    • Urinary incontinence
  • Other symptoms after severe poisoning include: hyperthermia (fever) or hypothermia (too low body temperature), dyspnea (difficult breathing), disorientation, cramps or spasms (sudden, involuntary contractions of muscles or hollow organs).
  • Symptoms appear a few hours after exposure, but depend strongly on the formulation, the dose and the kind of contact (skin, inhalation, ingestion etc).
  • Sustained skin exposure can cause local dermatitis (skin irritation) with pruritus (itching) and erythema (red skin).
  • Mucous membranes are particularly sensitive to synthetic pyrethroids, e.g. in the nose and the respiratory system (coughing), in the eyes (conjunctivitis), genital organs, etc.
  • After excessive inhalation of synthetic pyrethroids patients can develop allergic sensitization with asthmatic symptoms. In extreme cases, sustained inhalation of high doses can cause respiratory paralysis and death.
  • Cats can develop many of the previously mentioned symptoms 1 to 72 hours after off-label treatment with permethrin-containing products (e.g. spot-ons for dogs). Deaths have also been reported.
  • As a general rule, young animals are more sensitive to overdosing and react stronger. 
  • A frequent administration error in dogs is partial administraton to small dogs of spot-ons approved for large dogs.

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

  • Do not administer permethrin topically (spot-on, shampoos, soaps, sprays, etc.) in case of extended skin lesions: this can lead to an excessive absorption through the damaged skin.
  • Pour-ons containing permethrin and other synthetic pyrethroids can be irritant for cattle. This can be particularly annoying when handling dairy cows for milking.
  • In small dogs paresthesia (skin sensation of tingling, tickling, prickling) can happen at the therapeutic dose, which usually disappears in 12 to 24 hours.
  • Toxic effects can be potentiated after simultaneous exposure to organophosphates or other synthetic pyrethroids.
  • In horses permethrin can extend the effects of barbiturates.
  • Permethrin is used in numerous spot-ons (= pipettes, squeeze-ons) for dogs that contain high concentrations of permethrin (up to 65%!). This results in dermal doses of up to 100 mg/kg. Mistakes during administration (e.g. overestimating the dog's weight, or using a spot-on vial for larger dogs) can easily double this dose. Comparable pour-on products for cattle can have an irritant effect on individual animals already at doses <10 mg/kg. It is therefore not surprising that some dogs (e.g. breeds with sensitive skin, old animals, etc.) do not tolerate such high permethrin doses.
  • Never use spot-on or other products on cats that are approved only for dogs: permethrin is toxic to cats!
  • Never use spot-on for large dogs on small dogs. It happens that some users want to save money buying large spot-ons for treating smaller dogs twice or more times. The risk of overdosing is considerable, either due to erroneous calculations or to unskilled manipulation. Remaining product in opened spot-on vials can deteriorate.

Antidote and Treatment of Permethrin Intoxication

  • There is no antidote for permethrin poisoning.
  • Treatment consists in preventing further exposure together with supportive and symptomatic measures.
  • In case of dermal exposure rinse the skin with abundant water and soft detergents.
  • After accidental ingestion administer activated charcoal (2g/kg), magnesium sulphate or sodium sulphate (0.5 mg/kg in a 10% aqueous solution)
  • Spasms can be treated with anticonvulsants (e.g. diazepam). If ineffective, fenobarbital or pentobarbital can be tried.
  • Hypersalivation can be treated with atropine.
  • In case of strong vomit and/or diarrhea rehydration measures should be considered.
  • Calcium gluconate and vitamins of the B complex can be used to protect the liver.

Pharmacokinetics of Permethrin

  • Topically administered permethrin remains mostly on the hair-coat of the treated animals and is very poorly absorbed through the skin. In contrast with natural pyrethrins and older synthetic pyrethroids, permethrin is quite resistant to UV-light, which allows a residual effect between 5 and 10 days after topical administration.
  • Treated animals can ingest permethrin through licking or grooming. Absorption to blood is low. The absorbed permethrin is quickly metabolized in the liver to non-toxic metabolites that are excreted through urine. This is done by a specific enzyme called glucuronidase. However, cats lack this enzyme and cannot metabolize permethrin and other synthetic pyrethroids. This is why permethrin and most other synthetic pyrethroids are toxic to cats.
  • Permethrin products are approved for use on dairy animals and on laying hens in many countries.

Environmental Toxicity of Permethrin

  • Permethrin, as all synthetic pyrethroids is extremely toxic to fish and aquatic invertebrates. For this reason disposal of permethrin residues (e.g. in empty containers) in watercourses must be absolutely avoided. Disposal of old dip wash charged with permethrin (or other synthetic pyrethroids) into watercourses is strictly forbidden worldwide because it would have catastrophic consequences for fish and other aquatic animals. There are countries where products for livestock dipping containing synthetic pyrethroids have been withdrawn by the regulatory authorities for this reason.
  • In contrast with organophosphates permethrin (as most synthetic pyrethroids) is not toxic to birds.
  • Correct use on dogs and livestock is unlikely to result in any significant environmental pollution.
  • There is a certain environmental risk of water pollution from run-off after pour-on administration to large cattle herds. However this risk is substantially lower than the one associated with the use of permethrin (or other synthetic pyrethroids) as a crop pesticide.
  • Permethrin is quite resistant to photodegradation, i.e. exposed to sunlight it breaks down rather slowly.
  • Permethrin is almost insoluble in water and tends to bind to soil particles. Therefore groundwater contamination is unlikely to occur. Persistence in water depends on pH and temperature. Under usual conditions persistence in water is ~5 days.
  • Persistence in soils is moderate but depends strongly on their structure. It breaks down faster in sandy soils with scarce organic material than in clayey soils or those rich in organic material.
  • Soil bacteria contribute to the biodegradation of permethrin.
  • Permethrin does not bioaccumulate.

Additional information

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

  • Permethrin belongs to the chemical class of the synthetic pyrethroids and to the so-called type-I pyrethroids (without a cyano group in their molecular structure).
  • Commercial products with permethrin may use different qualities regarding the cis-trans isomer ratios, usually 80:20, 40:60 or 25:75.
  • Permethrin is used in human medicines (e.g. against lice and mange mites).
  • Permethrin is used in crop pesticides.
  • Permethrin 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 permethrin.

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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