FIPRONIL: Safety Summary for Veterinary Use

WHO Acute Hazard classification of pesticides: Class II, moderately hazardous.


Mechanism of action of Fipronil

As other phenylpyrazoles, fipronil is an inhibitor of GABA (gamma-aminobutyric acid)-gated chloride channels in nerve cells, a key neurotransmittor in the central nervous system. The nervous system of exposed parasites (fleas, ticks, mites, etc.) is overexcited, which kills them rather quickly.

This mechanism exists not only in insects but also in mammals and other vertebrates. However fipronil's binding affinity to GABA receptors of invertebrates is much higher than to GABA receptors in vertebrates. For this reason it is significantly less toxic to mammals than to insects and other pests.


Acute Toxicity and Tolerance of Fipronil

  • LD50 acute, rats, p.o. 97 mg/kg
  • LD50 acute, dogs, p.o. 640 mg/kg
  • LD50 acute, chicken, p.o. 11.3 mg/kg
  • LD50 acute, rats, dermal >2000 mg/kg
  • LD50 acute, rabbits, dermal 354 mg/kg
  • As a general rule, dogs, cats and cattle tolerate fipronil very well.
  • Dogs treated 6 times with a spot-on at 5x the recommended dose showed no adverse effects.
  • Puppies treated twice with a spot-on at 2x the recommended dose showed no adverse effects.
  • In a one-year study fipronil was administered daily to dogs in gelatin capsules at 0.2, 2, or 5 mg/kg. At doses of ≥2 mg/kg several neurotoxicity signs were recorded and one animal died. The NOAEL was 0.2 mg/kg/day.


Toxic Symptoms caused by Fipronil Poisoning

  • The primary symptoms of intoxication with fipronil and other phenylpyrazoles affect mainly the Central Nervous System (CNS).
  • Most frequent symptoms are:
    • Ataxia (uncoordinated movements)
    • Hyperreactivity (exaggerated reaction to stimuli)
    • Tremor (uncoordinated trembling or shaking movements)
    • Cramps (sudden, involuntary contractions of muscles)
    • Convulsions
    • Abnormal gait
    • Seizure
  • Other symptoms reported after fipronil poisoning include twitching, nodding, aggression, sweating, nausea, lack of appetite, vomiting, headache, abdominal pain, dizziness, agitation and weakness.
  • 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).
  • In chronic toxicity studies in rats, liver, kidneys and thyroid gland were also affected.
  • As a general rule, young animals are more sensitive to overdosing and react stronger.
  • Besides erroneous dosing, overdosing can occur due to excessive licking after spot-on delivery to dogs and cats (particularly in cats due to intense grooming).
  • A frequent administration error in dogs is partial administration to small dogs of spot-ons approved for large animals.
  • A frequent administration error in cats is partial administration to cats of spot-ons approved only for dogs.

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

  • Fipronil can be slightly irritant for the skin and the eyes.
  • When using sprays or aerosols, excessive inhalation of some solvents (e.g. isopropanol) can cause serious problems in young or weak animals. This is not related to fipronil.
  • Never use spot-ons for dogs on cats; never use spot-ons for large dogs on small dogs. It happens that some users want to save money buying large tablets or spot-ons for treating smaller dogs (or even cats!) twice or more times. The risk of overdosing is considerable, either due to erroneous calculations or to unskilled manipulation. In addition, dog medicines may sometimes contain other ingredients that are toxic to cats.
  • Fipronil is not approved for use on livestock in many countries (e.g. US, EU, Australia) but is abundantly used on cattle in other countries (mainly in Latin America: Argentina, Brazil, Mexico, etc.), mainly in pour-ons. Most such products have withholding periods of 3-4 months for meat and are not approved for use on dairy cows. Unfortunately little is known about the target-animal safety of such pour-ons.
  • Never use on rabbits, particularly on young one, which seem to be particularly sensitive to fipronil.
  • Never use on chickens and other poultry: they are much more sensitive to fipronil than mammals. However ducks and other aquatic birds tolerate fipronil better.
  • Unless prescribed by a veterinary doctor, never use on dogs or cats products for livestock that are not explicitly approved for such use. There is a high risk of overdosing or of adverse drug reactions due to ingredients that are not tolerated by pets or are even toxic to them.

Antidote and Treatment of Fipronil Intoxication

  • There is no antidote for fipronil 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 stomach lavage as well as administration of active charcoal administration and laxatives is recommended.

Pharmacokinetics of Fipronil

  • Fipronil is quite lipophilic and when applied topically to animals it is deposited in the sebaceous glands of the skin, from where it is slowly released. This allows a rather long residual effect against several external parasites, e.g. fleas and ticks.
  • Absorption of topically administered fipronil is rather low in dogs and cats, usually not more than 5% of the administered dose. The absorbed fipronil is found predominantly in fatty tissues.
  • Treated animals can ingest fipronil through licking or grooming. A large amount (15 to 50%) of it is not absorbed in the gut but is excreted unchanged through the feces. The rest is absorbed into blood and is partially metabolized.
  • The primary metabolite is the sulfone derivative, which is substantially more toxic, both for parasites and for mammals. Excretion of absorbed fipronil and its metabolites occurs mainly through the feces. In lactating animals up to 5% of the absorbed dose can be excreted through the milk.

Environmental Toxicity of Fipronil

  • Fipronil is highly toxic to fish and aquatic invertebrates. For this reason disposal of fipronil residues (e.g. in empty containers) in watercourses must be absolutely avoided.
  • Fipronil is highly toxic to some birds (e.g. chicken) but not to other ones (e.g. ducks).
  • Fipronil is also highly toxic to bees. The EU has recently banned the use of fipronil as a pesticide in certain crops because it is suspected to be associated with the Bee Colony Collapse Disorder.
  • Fipronil is quite stable in soils, with a half-life of ~125 days.
  • Fipronil is almost insoluble in water. Sunlight quickly breaks down solved fipronil  (half-life <24 hours). Therefore it is unlikely to contaminate groundwater. 
  • Fipronil does not bioaccumulate.
  • Correct use on dogs, cats 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 fipronil as a crop pesticide.

Additional information

  • Fipronil belongs to the chemical class of the phenylpyrazoles.
  • Fipronil is not used in human medicines.
  • Fipronil is used in crop pesticides.
  • Fipronil is used in public and domestic hygiene as a biocide.
  • Click here for technical and commercial information on fipronil.

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.