Insect Growth Regulators
The insect growth regulators (IGR) or juvenile hormone (JH) analogs target insect growth and development at an early stage; by contrast, most ectoparasiticides used are adulticides. The IGRs specifically target insects and not mammalians because mammalians do not have a JH system. The effect of IGRs and JH analogs is to prevent reproduction by preventing metamorphosis of insect larvae into viable adults when such insecticides are applied to the larvae.
Methoprene
Methoprene (1-methylethyl (E,E)-11- methoxy-3,7,11-trimethyl- 2,4-dodecadienoate) has a chemical formula of C19H34O3, with a molecular weight of 310.48.
Courtesy of Dr. Ramesh Gupta and Dr. Robin Doss.
Methoprene is a racemic mixture of the R- and S-enantiomers in a 1:1 ratio, with its activity as a JH analog (growth regulator) being restricted to the S-enantiomer. Methoprene does not kill insects. Instead, it interferes with an insect’s life cycle and prevents it from reaching maturity and reproducing. S-methoprene is commonly used in ectoparasiticide products.
The acute oral LD50 of racemate and S-methoprene in rats is >5,000 mg/kg and is between 5,000 and 10,000 mg/kg in dogs. The acute dermal LD50 for both racemate and S-methoprene in rabbits is >2,000 mg/kg. These acute toxicity data suggest that S-methoprene is very safe to animals and humans. Methoprene can cause irritation to the mucous membranes and upper respiratory tract. It can be harmful by inhalation, ingestion, or skin absorption. Experimentally, dogs treated topically with ectoparasiticide products containing S-methoprene did not show any signs of toxicosis or reaction at the site of application.
Hydropene
Courtesy of Dr. Ramesh Gupta and Dr. Robin Doss.
Hydroprene (ethyl (2E,4E)-3,7,11-trimethyl-2,4-dodecadienoate) has a chemical formula of C17H30O2 with a molecular weight of 266.425.
Like methoprene, hydroprene is a racemic mixture of R- and S-enantiomers, and its activity as a JH analog is attributed to the S-enantiomer. The oral LD50 of racemate and s-hydroprene in rat is >5,000 mg/kg. Toxicity and safety profiles of hydroprene are similar to that of methoprene.
Pyriproxyfen
Courtesy of Dr. Ramesh Gupta and Dr. Robin Doss.
Pyriproxyfen (4-Phenoxyphenyl (R/S)-2-(2-pyridyloxy)propyl ether 2-[1-(4-phenoxyphenoxy)propan-2-yloxy]pyridine), has a chemical formula of C20H19NO3, with a molecular weight of 321.376.
Pyriproxyfen is a JH analog and an IGR affecting the embryonic, larval, and reproductive stages of insects. It prevents larvae from developing into adulthood, thus rendering them unable to reproduce. In veterinary medicine, pyriproxyfen is commonly used for flea control on household pets and for killing indoor and outdoor ants and roaches.
Pyriproxyfen has a low mammalian toxicity. At higher doses (>5,000 mg/kg), pyriproxyfen may affect the liver, alter cholesterol concentration, and cause anemia in animals.
Chitin Synthesis Inhibitors
Chitin is the main component of the outer shell (exoskeleton) of arthropods, such as insects and crustaceans. Insects grow by repeatedly molting or hatching and creating a new exoskeleton, and this requires the synthesis of chitin. Inhibitors of chitin synthesis can prevent this process. A few chitin synthesis inhibitors are diflubenzuron, flufenoxuron, and lufenuron.
Diflubenzuron
Courtesy of Dr. Ramesh Gupta and Dr. Robin Doss.
Diflubenzuron is an insecticide of the benzoylurea class. It has a chemical structure of C14H9ClF2N2O2, with a molecular weight of 310.68.
Diflubenzuron is a widely used larvicide for the control of mosquitoes and it has been approved by the WHO. It is also used as a larvicide in cattle to control fly populations. The mechanism of action of diflubenzuron involves inhibiting the production of chitin. It triggers insect larvae to molt early without a properly formed exoskeleton, resulting in the death of the larvae. Diflubenzuron has no toxic effects on adult insects.
The acute toxicity of diflubenzuron is very low. The oral LD50 in rats and mice is >4,600 mg/kg. It is not a skin irritant or a skin sensitizer.
Flufenoxuron
Courtesy of Dr. Ramesh Gupta and Dr. Robin Doss.
Flufenoxuron (N-[[4-[2-chloro-4-(trifluoromethyl)phenoxy]-2-fluorophenyl] carbamoyl]-2,6-difluorobenzamide) has a chemical formula of C21H11ClF6N2O3 and a molecular weight of 488.77.
Flufenoxuron is of very low toxicity to humans and mammals. The acute oral LD50s are >5000 mg/kg in male and female rats, ICR mice and dogs and >3000 mg/kg in male and female STCF1 mice. The acute dermal LD50 is >2000 mg/kg in male and female rats and mice. Due to high bioaccumulation, it is toxic to fish.
Lufenuron
Courtesy of Dr. Ramesh Gupta and Dr. Robin Doss.
Lufenuron (1-[2,5-dichloro-4-(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-3-(2,6-difluorobenzoyl)urea) is a benzoylphenyl urea, which has a chemical formula of C17H8Cl2F8N2O3, with a molecular weight of 511.15.
Lufenuron is an active ingredient in flea control, and is also used in combination with milbemycin oxime for heartworm and ringworm and as an anthelmintic. Lufenuron is stored in the animal’s body fat and transferred to adult fleas through the host’s blood. Adult fleas transfer it to their eggs through their blood and to hatched larvae feeding on their excrement. Lufenuron is classified as an insect development inhibitor (IDI). Lufenuron does not kill adult fleas. It inhibits the production of chitin in insects, and without chitin, a larval flea will never develop a hard exoskeleton. As a result, the flea's inner organs are exposed to air and the insect dies from dehydration soon after hatching or molting. In cats, lufenuron must be given orally once a month or injected every 6 months to be effective.
Lufenuron is safe for its use in dogs and cats, as its acute oral toxicity in rats and mice is >2,000 mg/kg, and it is nonirritating to the skin and eyes.
