PYRIPROXYFEN: Safety Summary for Veterinary Use

WHO Acute Hazard classification of pesticides: U, unlikely to present acute hazard in normal use


Mechanism of action of Pyriproxyfen

Pyriproxyfen is a Juvenile Hormone Analogue (JHA) acting as an insect development inhibitor (also called Insect Growth Regulator = IGR) effective against numerous insect species, but with no effect whatsoever on ticks or mites. It only interferes with the molt from pupae to adults, i.e. it does not kill insect larvae and consequently it cannot be used against various myiases.

Pyriproxyfen and other JHAs suppress or stimulate the expression of various genes involved in insect metamorphosis otherwise regulated by natural juvenile hormone. Depending on which gene is affected different biochemical and cellular effects will result. The bottom line is that development is disturbed and interrupted. Since these biochemical processes do not occur in mammals, pyriproxyfen and most other JHAs can be considered as rather safe for humans, pets and livestock.

In dogs and cats pyriproxyfen it is mostly used in combination with flea adulticides (e.g. cyphenothrin, dinotefuran, etofenprox, fipronil, imidacloprid, permethrin, etc.) in numerous spot-ons (= squeeze-on = pipettes), as well as in shampoos, soaps, sprays, etc. It is used mainly to add efficacy against the developmental stages of the fleas (larvae, eggs), since most flea adulticides have an insufficient impact on the developmental stages in the pets' environment. From the safety point of view, the adulticides in such products are much more capable of causing adverse drug reactions than pyriproxyfen.


Acute Toxicity and Tolerance of Pyriproxyfen

  • LD50 acute, rats, oral >2000 mg/kg
  • LD50 acute, dogs, oral: >2000 mg/kg
  • Pyriproxyfen is not carcinogenic, teratogenic or mutagenic.
  • It is non-irritating to skin and eyes.
  • Dogs and cats tolerate pyriproxyfen very well.
    • In a tolerance study in cats treated at 300x the therapeutic dose no adverse drug reactions were recorded.
    • Kittens 4 - 6 weeks old tolerated up to 12x the recommended dose without adverse durg reactions.
    • Puppies 4 weeks old treated at 3x and 9x the recommended dose showed no adverse drug reactions.
  • Usual therapeutic dose (topical) in dogs is 0.5 - 13.3 mg/kg
  • Usual therapeutic dose (topical) in cats is 5 - 70 mg/kg

Toxic Symptoms, Side Effects, Adverse Drug Reactions (ADRs) and Warnings

  • As a general rule, intoxications with pyriproxyfen are very infrequent due to its low toxicity, the high safety margin and the excellent tolerance in pets.
  • After been treated with moderate to high doses of pyriproxyfen some animals were less active and gained weight less quickly. Some had diarrhea, unusual breathing, and loss of muscle control.
  • Dogs fed a high dose of pyriproxyfen vomited occasionally during the first day.
  • In pets, since it is mainly used in mixtures with other adulticidal insecticides, observed ADRs are more likely to be caused by other active or inert ingredients than by pyriproxyfen.

Antidote and Treatment of Pyriproxyfen Intoxication

  • There is no antidote for pyriproxyfen poisoning.
  • Treatment consists in preventing further exposure together with supportive and symptomatic measures.


Pharmacokinetics of Pyriproxyfen

  • After topical administration pyriproxyfen is distributed throughout the hair coat within 24 hours. After treatment at the recommended therapeutic dose (2-5 mg/kg) the highest concentration was observed at the application site (~800 mcg/kg) and at the back and the flanks (~66 mcg/kg). It remained detectable in the hair coat for about 42 days. It was stored in the hair follicles from where it was continuously released during a period of ~3 months.
  • Absorption through the skin is very low. Bioavailability reached ~37%, and the highest plasma concentration (2.8 ng/ml) was measured 1-3 days after administration. Half-life was 6 days.
  • In rats, pyriproxyfen concentrations were found to be highest in the fat, without evidence of accumulation. Pyriproxyfen was highly and quickly metabolised and excreted into faeces and urine, with the major route of excretion being via the faeces.

Environmental Toxicity of Pyriproxyfen

  • Pyriproxyfen is practically nontoxic to birds and mammal.
  • Pyriproxyfen is moderately to highly toxic to some fish species and to some aquatic arthropods such as insects and crustaceans. However, it is very poorly soluble in water, which limits the risk of harm to the aquatic fauna.
  • Pyriproxyfen is highly sensitive to sunlight and soil microbes. When exposed to sunlight, the half-life of pyriproxyfen is 6.8 to 16 days on soil surfaces and 3.7 to 21 days in water, more slowly in dark water. In water without oxygen half-life reached 346 days.
  • Pyriproxyfen binds strongly to soil particles. It is unlikely to move into ground water.
  • Pyriproxyfen does not cumulate in the environment or in the food chain.
  • Correctly used in dogs and cats it is unlikely to be detrimental for the environment.


Additional information

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

  • Pyriproxyfen is an insect growth regulator belonging to the group of the Juvenile Hormone Analogues.
  • Pyriproxyfen is not used in human medicines.
  • Pyriproxyfen is moderately used in crop pesticides.
  • Pyriproxyfen is used in public and domestic hygiene, mainly against mosquito larvae in water.
  • 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 pyriproxyfen.

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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