ETOFENPROX: Safety Summary for Veterinary Use
WHO Acute Hazard classification: class U, unlikely to present acute hazard.
Mechanism of action of Etofenprox
Etofenprox is a so-called pyrethroid ether pesticide, whereas most synthetic pyrethroids are pyrethroid esters. However, the mode of action of both types is basically the same. 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 Etofenprox
- LD50 acute, rats, p.o. >2000 mg/kg.
- LD50 acute, rats, dermal, >2000 mg/kg
- LD50 acute, dogs, dermal, >5000 mg/kg
- Etofenprox is less irritant than most pyrethroid esters (e.g. cyphenothrin, phenothrin, permethrin, etc.).
- Toxicity to mammals (including dogs and cats) can be higher in case of sustained skin or inhalation exposure, or after direct contact with open wounds.
- As a general rule, dogs tolerate etofenprox and most synthetic pyrethroids very well, since toxicity is about 1000x higher to insects and other arthropods than to mammals.
- Etofenprox seems to be less toxic for cats that other synthetic pyrethroids. BUT: cats are more susceptible to synthetic pyrethroids than dogs and do not tolerate doses that are harmless for dogs. This is associated with glucuronidase deficiency in cats, the enzyme responsible for breaking down most synthetic pyrethroids in the organism in a process called glucuronidation. As a consequence, synthetic pyrethroids remain much longer in the cat's organism than in dogs or other mammals.
Toxic Symptoms caused by Etofenprox Poisoning
- The primary symptoms of intoxication with most synthetic pyrethroids affect mainly the nervous and muscular systems. However, the liver was also a major target organ for the toxicity of etofenprox in dogs. Other target organs for toxicity in rats were the kidney, thyroid and hematopoietic (blood building) system.
- 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)
- 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.
- As a general rule, young animals are more sensitive to overdosing and react stronger.
- A frequent administration error in dogs is partial administration to small dogs of spot-ons approved for large dogs.
Etofenprox Side Effects, Adverse Drug Reactions (ADRs) and Warnings
- Adverse drug reactions are similar to those of intoxication previously described, but usually milder.
- Do not administer etofenprox topically (spot-on, shampoos, soaps, sprays, etc.) in case of extended skin lesions: this can lead to an excessive absorption through the damaged skin.
- Toxic effects can be potentiated after simultaneous exposure to organophosphates or other synthetic pyrethroids.
- Animals treated topically can ingest etofenprox through licking or grooming (particularly cats).
- Never use spot-ons or other products on cats that are approved only for dogs: synthetic pyrethroids can be toxic to cats.
- Never use spot-ons 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.
- Serious problems with adverse reactions after use of certain flea and tick spot-ons have been reported in the USA, especially on cats and small dogs. According to a report by the EPA from 2010, most problems occurred with spot-ons containing permethrin, phenothrin, cyphenothrin (all are synthetic pyrethroids) and amitraz, not approved for use on cats but erroneously used on them. There have been numerous overdosing cases of small dogs too, apparently because some users buy large vials for big dogs but use them several times in smaller dogs to save money. It seems also that small dogs are more sensitive than large ones and don't tolerate the treatment as large dogs. It also seems that some insufficiently investigated inert ingredients (e.g. solvents) in the formulations are not as harmless as they were supposed to be.
- Several spot-ons (= pipettes, squeeze-ons, drops, etc) for dogs and cats contain high concentrations of etofenprox (>50%!). This results in dermal doses of >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 containing also synthetic pyrethroids can have an irritant effect on individual animals already at doses <10 mg/kg. It is therefore not surprising that some dogs or cats (e.g. breeds with sensitive skin, old animals, puppies, kittens etc.) do not tolerate such high etofenprox doses.
Antidote and Treatment of Etofenprox Intoxication
- There is no antidote for etofenprox 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 Etofenprox
- Topically administered etofenprox remains mostly on the hair-coat of the treated animals and is very poorly absorbed through the skin.
- However, treated animals can ingest etofenprox through licking or grooming. In dogs, ingested etofenprox was quickly but incompletely (14 to 51%) absorbed to blood.
- Absorbed etofenprox is mostly metabolized in the liver to non-toxic metabolites that are excreted through urine. Excretion of parent etofenprox and its metabolites is completed up to 90% in the feces and the rest in urine 5 days after oral administration.
Environmental Toxicity of Etofenprox
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- Etofenprox, as all synthetic pyrethroids is highly toxic to fish and aquatic invertebrates. For this reason disposal of etofenprox residues (e.g. in empty containers) in watercourses must be absolutely avoided.
- In contrast with organophosphates etofenprox (as most synthetic pyrethroid) is not toxic to birds.
- Correct use on dogs or cats is unlikely to result in any significant environmental pollution.
- Etofenprox is moderately stable to photodegradation, but not as UV-resistant as modern ester-pyrethroids (e.g. cypermethrin, deltamethrin, permethrin, etc).
- Etofenprox breaks down in aerobic soil (i.e. soil containing oxygen) with a half-life of 1-3 weeks.
- Etofenprox is poorly soluble in water.
- Soil bacteria contribute to the biodegradation of etofenprox.
- Etofenprox does not bioaccumulate.
- Etofenprox belongs to the chemical class of the synthetic pyrethroids and to the so-called non-ester pyrethroids, or ether pyrethroids.
- Etofenprox is not used in livestock.
- Etofenprox is not used in human medicines.
- Etofenprox is used in crop pesticides.
- Etofenprox is used in public or domestic hygiene as a biocide against many household pests (ants, cockroaches, termites, etc.) and for vector control (e.g. against mosquitoes)
- 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 etofenprox.
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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