Growth Regulators of insects (IGRs) or ticks are parasiticides that interrupt the development of immature stages to adults. They do it in two major ways:
- Interfering with the molting process of immature stages such as larvae and nymphs.
- Preveting hatching of eggs deposited by adult females.
In both cases the life-cycle is interrupted and the population declines or is decimated.
IGRs are also called Insect Development Inhibitors (IDI), or Insect Growth Disruptors (IGDs).
Development of insects and ticks is regulated by two major hormones: ecdysone and juvenile hormone. In a nutshell, ecdysone brings the larvae to moult to the next larval stage if there is enough juvenile hormone. If not, larvae initiate a moult to the adult stage.
In dogs and cats they are used mainly against fleas, either alone or in combination with adulticides, applied both on and off the animals.
Use in horses is very scarce.
All Insect Growth Regulators are more or less veteran antiparasitics, i.e. they have lost patent protection. Many of them are available as generics manufactured by numerous chemical companies (typically in China, India, Israel, Brasil, etc.).
Click here for a general introduction to ectoparasiticides and their most important features.
Active ingredients, mode of action, characteristics and formulations of Insect Growth regulators
Strictly speaking Growth Regulators (or Development Inhibitors) are not a specific "chemical class" of parasiticides, but rather a "functional class". Chemically they belong to various unrelated chemical classes. But all have the same effect on parasites, they interfere with their development.
There are two major types of development inhibitors, depending on the physiological process they interfere with:
- Chitin Synthesis Inhibitors (= CSI)
- Juvenile Hormone Analogues (= JHA)
Chitin Synthesis Inhibitors
Chitin is a long-chain polymer of a glucose derivative called N-acetylglucosamine. It is a major constituent of the cuticle of insects, ticks, mites and other arthropods, which itself is an essential part of their external skeleton (exoskeleton). Chitin is also the major constituent of the cell wall of fungi where it has a similar function as cellulose in plants.
Since the exoskeleton of arthropods is rigid, for growing in size they have to molt, i.e. get rid of the old small "skin", expand, and produce a larger one. In this process a new cuticle has to be produced, which needs chitin that makes it hard. Chitin synthesis inhibitors hamper the synthesis and/or the correct deposit of chitin in the cuticle: larvae or nymphs cannot properly molt and die during the process.
The inhibition of egg hatching is due to the fact that young larvae develop inside the egg and have to moult before hatching. If an adult female was treated with a chitin synthesis inhibitor significant amounts of it are passed to the eggs. The embryo can develop quite normally but it dies during the first moult, still inside the eggshell.
Most Chitin Synthesis Inhibitors belong to the benzoylphenylureas (BPU) or simply benzoilureas. The benzoylureas most used on livestock and pets are the following ones:
- Diflubenzuron: Broad-spectrum insect larvicide. Used against houseflies, and against blowfly strike and lice in sheep.
- Fluazuron: Specific tick development inhibitor. Used only in cattle against cattle ticks.
- Lufenuron: Broad-spectrum insect larvicide. Used only against fleas in dogs and cats.
- Triflumuron: Broad-spectrum insect larvicide. Used against houseflies, and against blowfly strike and lice in sheep.
The benzoilureas diflubenzuron, lufenuron and triflumuron are broad-spectrum insect larvicides, i.e. they are effective against the immmature stages of many insects, but not of ticks or mites. Fluazuron has no effect on insects at the usual dosage, but is highly effective against tick larvae. In fact it is the only tick development inhibitor currently available.
Diflubenzuron was the first benzoylurea larvicide, discovered already in the 1970's. It is moderately used in livestock, mainly as pour-on against blowfly strike and lice in sheep (currently mostly abandoned due to resistance), as a feed-throug additive or as a slow-release bolus against hornfly larvae in cattle dung, and also as a concentrate for manure and waste treatment against houseflies and nuisance flies. It is not used in pets. It is also used as an agricultural and hygiene pesticide.
Triflumuron is used in livestock in a few countries (e.g. Australia and New Zealand), mainly as pour-on against blowfly strike and lice in sheep (currently mostly abandoned due to resistance) and as concentrate for manure and waste treatment against houseflies and nuisance flies. It is not used in pets. It is also used as an agricultural and household pesticide.
Lufenuron is exclusively used against fleas in dogs and cats. It is available as tablets for dogs, alone or in combination with other active ingredients, as well as an oral suspension and injectable for cats. It is also used as an agricultural pesticide. It acts systemically, i.e. after ingestion or injection it gets into the blood of the pet from where it reaches the bloodsucking fleas. The eggs of these fleas will not hatch.
Fluazuron is a special case, because it is only effective against ticks. It is used exclusively in cattle as a pour-on for population control of cattle ticks (Boophilus = Rhipicephalus microplus) and blue cattle ticks (Boophilus = Rhipicephalus decoloratus), alone or combined with other parasiticides. It is not adequate for knocking down acute tick infestations, but is an excellent preventative. Protection of beef cattle can last up to 12 weeks. Protection of breeding cows is shorter (usually 6 to 8 weeks) because it is partially passed to the calves through the mother's milk. This way the calves do not need to be treated.
Another less relevant benzoylurea is flufenoxuron used in sheep in a few countries (e.g. South Africa) as pour-on against blowfly strike and lice, but is not used in pets. It is also used as an agricultural and hygiene pesticide.
Juvenile Hormone Analogues (JHA)
These compounds mimic the activity of natural juvenile hormone during insect development. They are also called juvenoids and juvenile hormone mimics. They interfere with the last larval molt to pupae or adults. The effect is that either pupae die, or no mature adults develop, which progressively decimates the population. Most JHA have a broad spectrum of activity against insects, but no effect on ticks or mites.
The Juvenile Hormone Analogues most used on livestock and pets are the following ones:
- Methoprene: Moderately used in pets, rather scarce use in livestock.
- Pyriproxyfen: Scarcely used in pets. Not used in livestock.
Methoprene is used in livestock for direct manure treatment against larvae of houseflies and nuisance flies, but also in various feed-through formulations (e.g. mineral blocks, slow-release boluses) for cattle against hornfly larvae. It is also used to control fleas in dogs and cats, either for on-animal use in spot-ons, sprays , etc. mixed with various flea adulticides; or for off-animal use in various products for the environmental control of fleas on pet premises (carpets, furniture, etc). It is quickly degraded by UV-light and consequently not very persistent if the animals are exposed to sunlight. It is also used in agriculture and against household pests.
Pyriproxyfen is effective at extremely low concentrations and is resistant to sunlight, i.e. it is very persistent and residual effect can last for 6 months and beyond. It is used in various products for on and off-animal control of pet fleas in dogs and cats, alone or in mixtures with various adulticides. It is also used in agriculture and against household pests.
Another less relevant JHA is fenoxycarb, used in a few pet products, mostly mixed with flea adulticides. It is also used in agriculture. Another JHA not used on animals but in public and domestic hygiene is hydropene.
Other insect development inhibitors
A few development inhibitors are neither Chitin Synthesis Inhibitors, nor Juvenile Horme Analogues:
- Cyromazine: Chemical class: triazine. Specific larvicide. Used against houseflies in poultry and livestock operations, and against blowfly strike in sheep. In a few countries is is also used as a feed-through larvicide in horses.
- Dicyclanil: Chemical class: pyrimidine derivative. Specific larvicide. Used only against blowfly strike in sheep.
Cyromazine is a narrow spectrum larvicide effective against dipteran larvae (flies, mosquitoes, etc.), fleas and a few other insect species. Its mode of action is not completely elucidated. Instead of inhibiting the chitin synthesis it seems to interfere with its deposition in the cuticle immediately after the molt. It is used in sheep against blowfly strike in concentrates (for dipping, spraying and jetting) or as a pour-on or spray-on, alone or in mixtures with other parasiticides. It can protect sheep from blowfly strike for up to 12 weeks. For the control of houseflies it is also used as feed-thtough larvicide for poultry, and as concentrate for direct manure treatment in livestock operations. Being quite specific against houseflies it ist not toxic to many beneficial insects that live in livestock manure. It is not used in pets, but there are crop pesticides with cyromazine.
Dicyclanil is another narrow spectrum larvicide with a similar spectrum as cyromazine. Chemically it is very similar to cyromazine but belongs to another chemical class. It is used exclusively in sheep as pour-on or spray-on for the prevention of blowfly strike and other cutaneous myiasis (e.g. Wohlfahrtia magnifica). Protection against blowfly strike lasts for up to 24 weeks, depending on sheep breeds and climatic conditions. It is neither used in pets, nor in crop protection or hygiene.
Safety of IGRs
Most Insect Growth Regulators have a very low mammalian toxicity. A major reason is that they act upon molecular mechanisms that exist only in arthropods. Consequently they are substantially safer for humans, livestock and pets than most other classic ectoparasiticides. They are also quite safe for birds, fish, reptiles, amphibians and other vertebrates.
However, broad spectrum IGRs such as benzoylureas and Juvenile Hormone Analogues act at very low concentrations and can be highly toxic to soil and aquatic invertebrates in the environment (mainly arthropods), including many beneficial species. Several ones (e.g. pyriproxyfen) are quite persistant in the environment. Correctly used in livestock and pets they should not bear undue risks for the environment. But accidental contamination with concentrates of such products can seriously damage the environment, since many soil and aquatic arthropods are at the base of the food chain, which would be abruptely interrupted.
Those used for manure treatment against housefly larvae can negatively affect the populations of other beneficial arthropods, predators of housefly larvae, or dung feeding species that are natural recyclers of manure. A notable exception is cyromazine that is quite specific against dipteran larvae and does not harm the other beneficial arthropods in dung.
Additional specific information (toxicity, intoxication symptoms, adverse drug reactions, antidote, etc.) on the safety for veterinary use of certain IGRs is available in specific articles in this site:
General safety information for 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 livestock, horse or poultry products on dogs and/or cats, unless explicitly approved for dogs and/or cats too. Without reliable use instructions they can be easily overdosed, and pets may not tolerate formulations developed for use on livestock, horses and/or poultry. Some active ingredients may be toxic to particular animals.
Never use agricultural or hygiene products on livestock, horses, poultry or pets, unless explicitly approved for veterinary use, which is quite unusual. Even if the specific active ingredient is approved for some veterinary use. The formulations for agricultural and/or hygiene use are mostly different than those for veterinary use and may be toxic to or not be tolerated by animals.
It is obvious that veterinary medicines are not intended for and should never be used on humans!!!
Resistance of parasites to IGRs
There are numerous parasite species with confirmed field resistance to various IGRs. They include sheep lice (Bovicola = Damalinis ovis) and blowflies (Lucilia cuprina and L. sericata) resistant to benzoylureas (diflubenzuron and triflumuron) in Australia and New Zealand; cattle ticks (Rhipicephalus microplus) resistant to fluazuron in Australia and Brazil, and houseflies resistant to diflubenzuron, triflumuron and methoprene, and tolerant (i.e. slightly resistant) to cyromazine in various countries. There are also reports on mosquito resistance to methoprene
Resistance to some benzoylureas (diflubenzuron and triflumuron) and to methoprene can reach factors of >100, whereas cyromazine resistance factors are seldom >10 and may recede if product usage is interrupted.
Curiously, the massive use of cyromazine against blowfly strike in Australia, New Zealand, UK and Ireland for more than 40 years after its introduction (30 years in UK and Ireland), did not result in development of serious resistance by these flies. This although such flies developed resistance to other larvicides such as organophosphates and benzoylureas in not much more than 10 years after their introduction. The reasons for this are still not completely elucidated.
However, in 2020 resistance has been reported in two field strains of Lucilia cuprina in Australia reaching in vitro resistant factors of 13 to 25 when compared with suscetible dicyclanil and cyromazine strains, respectively. In-vivo studies showed that protection against re-infestation was reduced by 69% to 78% when compared with the claims of the manufacturer. These strains also showed a 55% and 33% reduction of the length of protection after treatment with commercial products based on cyromazine and ivermectin, respectively.
A personal message
During my years in Ciba-Geigy and Novartis (1984-1998) I was heavily involved in the discovery and development of three of the IGRs previously mentioned, dicyclanil, fluazuron and lufenuron. If you are interested in such "insider" stories you can visit the following articles in this site: