WHO Acute Hazard classification of pesticides: Not listed

Mechanism of action of Pyriprole

As other phenylpyrazoles, pyriprole 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 pyriprole'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 Pyriprole

• LD50 acute, rats, p.o. >300 mg/kg
• LD50 acute, rats, dermal >2000 mg/kg.
• Rats treated orally at 20 mg/kg/day during 28 days showed increased liver size and necrotic hepatocytes.
• As a general rule, dogs tolerate pyriprole very well.
• In one study, dogs treated topically (spot-on) at 3x the therapeutic dose monthly during 6 consecutive months a few dogs showed uncoordinated movements and unsteadiness that disappeared 3 hours after treatment.
• In another study, out of 8 dogs treated topically (spot-on) at 5x the therapeutic dose one dog showed transient ataxia (uncoordinated movements), trembling, panting and convulsions that disappeared 18 hours after administration. 
• In another study dogs treated topically (spot-on) once at 10x the therapeutic dose showed clinical symptoms including muscular contractions, seizures, unsteadiness, difficult breathing, vomiting, loss of appetite and reduced weight gain. Al symptoms disappeared 48 hours after treatment, excepting loss of appetite.

Toxic Symptoms caused by Pyriprole Poisoning

• The primary symptoms of intoxication with pyriprole 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

• Sustained skin exposure can cause local dermatitis (skin irritation) with pruritus (itching) and erythema (red skin).
• In chronic toxicity studies in rats, liver 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.
• A frequent administration error in dogs is partial administration to small dogs of spot-ons approved for large animals.

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

• Pyriprole can be slightly irritant for the skin and the eyes.
• The most frequent side effects at the therapeutic dose are transient local skin reactions: itching, hair loss, and light cosmetic effects on the hair coat (e.g. clogging).
• After licking the application site transient hypersalivation (drooling) has been reported as well as sticky and tangled appearance of hair for up to 24 hours.
• Never use spot-ons for large dogs in 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.
  

Antidote and Treatment of Pyriprole Intoxication

• There is no antidote for pyriprole 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 Pyriprole

• Pyriprole is quite lipophilic and when applied topically to animals it spreads quickly in the hair coat within 21 hours and 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 pyriprole is slow and rather low in dogs, usually not more than 5% of the administered dose. The absorbed pyriprole is quickly metabolized in the liver: no pyriprole was found in blood samples. Three weeks after administration ~45% of the administered dose still remained on skin and hair coat.
• Treated animals can ingest pyriprole through licking or grooming.
• The primary metabolites are the sulfone and sulfoxide derivatives.
• Excretion of absorbed pyriprole and its metabolites occurs mainly through the feces (up to 60%) and urine (up to 20%).

Environmental Toxicity of Pyriprole

• Pyriprole is highly toxic to aquatic invertebrates. For this reason disposal of pyriprole residues (e.g. in empty vials) in watercourses must be absolutely avoided.
• Pyriprole is not susceptible to photodegradation.
• Since pyriprole is only used on dogs, little is known about its environmental fate and toxicity.
• Correct use on dogs is unlikely to result in any significant environmental pollution.

Additional information

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

• Pyriprole belongs to the chemical class of the phenylpyrazoles.
• Pyriprole is not used in livestock.
• Pyriprole is not used in human medicines.
• Pyriprole is not used in crop pesticides.
• Pyriprole is not used in public and 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 pyriprole.