What are phenylpyrazoles?
Phenylpyrazoles are a relatively modern chemical class of pesticides introduced in the early 1990's both for agricultural and veterinary use. However, they can be considered as classic synthetic pesticides both by their mode of action and by their general features.
They have a broad spectrum of insecticidal and acaricidal activity and are effective against a number of veterinary parasites such as fleas, flies, ticks, lice and mites. They are not systemic and have a tarsal activity, i.e. they act by contact.
Fipronil, the first phenylpyrazole introduced in the market has already lost patent protection and generics are available from numerous chemical companies (typically in China, India, Israel, Brazil, etc.).
Click here for a general introduction to ectoparasiticides and their most important features.
Mode of action and characteristics of phenylpyrazoles
Phenylpyrazoles are inhibitors of GABA (gamma-aminobutyric acid), a key neurotransmitter in the central nervous system. This mechanism exists not only in insects but also in mammals and other vertebrates. However phenylpyrazoles seem to be much less effective on GABA receptors in vertebrates than in invertebrates.
Phenylpyrazoles are quite lipophilic and when applied topically to animals they are deposited in the sebaceous glands of the skin from where they are slowly released. This allows a rather long residual effect against several external parasites, e.g. fleas.
The most relevant phenylpyrazoles for veterinary use are:
- Fipronil: insecticide and acaricide; used a lot in dogs and cats, less in livestock
- Pyriprole: insecticide and acaricide; used only in dogs
Delivery forms of phenylpyrazoles
Phenylpyrazoles most used formulations are ready-to-use spot-ons for use in pets against fleas and ticks. Fipronil spot-ons are probably the pet product category most sold worldwide. There are also mixtures with other parasiticidal active ingredients (e.g. insect development inhibitors, amitraz, etc.). So far, pyriprole is only sold as a spot-on for dogs.
Besides its veterinary usage, fipronil is extensively used as an agricultural and hygiene pesticide.
Safety of phenylpyrazoles
For livestock and pets, as well as for operators and pet owners, the safety risks when using phenylpyrazoles are comparable to those of using products with other chemicals such as organophosphates, amidines, pyrethroids, etc. Correctly used they should be well tolerated by the treated animals and should not bear unreasonable risks for humans.
However, care must be taken that children do not get in close contact with pets during the first days after treatment with such products (either spot-ons or sprays) containing phenylpyrazoles.
It is good to know that fipronil is not yet allowed for use on livestock in many countries (e.g. USA, EU, Australia, etc.), although a product efficient against resistant cattle ticks and horn flies would be quite useful. There are no official reasons to this, but presumably it has to do with prohibitive residues in beef. MERIAL introduced a fipronil pour-on for cattle in Brazil years ago, but not elsewhere. In the meantime, numerous generic fipronil pour-ons for cattle have been introduced in several Latin American countries. They have withholding periods of up to 12 weeks.
Regarding the environment, fipronil has been involved in cases of mass mortality of bees. As a consequence agricultural products with fipronil were temporarily withdrawn in several countries. In one case in France, a relation has been demonstrated between the use of seeds inadequately treated with fipronil and bee mortality. Such seeds produced fipronil dust that killed the bees. The use of such seeds was subsequently prohibited. Otherwise fipronil is highly toxic to fish, certain birds and aquatic invertebrates, and is relatively stable in the environment (av. half-life in soil = 125 days).
Additional specific information (toxicity, intoxication symptoms, adverse drug reactions, antidote, etc.) on the safety for veterinary use of phenylpyrazoles is available in specific articles in this site:
General information on the safety of veterinary antiparasitics is available in specific articles in this site (click to visit):
- General safety of antiparasitics for domestic animals
- General safety of antiparasitics for humans
- General safety of antiparasitics for the environment
Never use products for livestock on dogs and cats unless they are explicitly approved for both livestock and pets. Pets may not tolerate livestock formulations.
Never use agricultural or hygiene products with this or any other active ingredient on livestock or pets, even if there are veterinary products with this same active ingredient approved for use on animals. The formulations for agricultural or hygiene use are different and may be toxic for livestock or pets.
It is obvious that veterinary products are not intended for and should never be used on humans!!!
Resistance of parasites to phenylpyrazoles
Various studies have confirmed cross-resistance between fipronil and organochlorines in natural horse fly (Musca domestica) and cockroach (Blatella germanica) populations. It seems that cattle ticks resistant to permethrin show cross-resistance with fipronil as well.
There are reports about cattle tick populations resistant to fipronil in Brazil, Mexico and Uruguay.
So far there are no confirmed reports on flea (Ctenocephalides spp) resistance to fipronil. But the number of cases of product failure is apparently increasing in several countries (e.g. the USA). Considering the extensive use of fipronil spot-ons for more than 15 years, the question now is not whether it will be confirmed, but when and where it will happen.