Chemical structure of permethrin
|Trade names||Nix, Rid, Elimite, others|
|Metabolism||Insects are more affected by permethrin than humans or dogs because they are unable to metabolise the toxins as quickly as humans and dogs. Cats, although not experiencing the full effect of permethrin, are more sensitive toward this toxin.|
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||391.29 g·mol−1|
|3D model (JSmol)|
|Density||1.19 g/cm3, solid g/cm3|
|Melting point||34 °C (93 °F)|
|Boiling point||200 °C (392 °F)|
|Solubility in water||5.5 x 10−3 ppm mg/mL (20 °C)|
Permethrin, sold under the brand name Nix among others, is a medication and insecticide. As a medication, it is used to treat scabies and lice. It is applied to the skin as a cream or lotion. As an insecticide, it can be sprayed on clothing or mosquito nets to kill the insects that touch them.
Side effects include rash and irritation at the area of use. Use during pregnancy appears to be safe. It is approved for use on and around people over the age of two months. Permethrin is in the pyrethroid family of medications. It works by disrupting the function of the neurons of lice and scabies mites.
Permethrin was discovered in 1973. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. The wholesale cost in the developing world is about US$0.02 to US$0.06 per gram. In the United States, a course of treatment costs US$25 to US$50, and it is available over the counter.
For treatment of scabies: Adults and children older than 2 months are instructed to apply the cream to the entire body from head to the soles of the feet. Wash off the cream after 8–14 hours. In general, one treatment is curative.
For treatment of head lice: Apply to hair, scalp, and neck after shampooing. Leave in for 10 minutes and rinse. Avoid contact with eyes.
In agriculture, permethrin is mainly used on cotton, wheat, maize, and alfalfa crops. Its use is controversial because, as a broad-spectrum chemical, it kills indiscriminately; as well as the intended pests, it can harm beneficial insects, including honey bees, and aquatic life.
Permethrin kills ticks and mosquitoes on contact with treated clothing. A method of reducing deer tick populations by treating rodent vectors involves stuffing biodegradable cardboard tubes with permethrin-treated cotton. Mice collect the cotton for lining their nests. Permethrin on the cotton instantly kills any immature ticks feeding on the mice.
Permethrin is used in tropical areas to prevent mosquito-borne disease such as dengue fever and malaria. Mosquito nets used to cover beds may be treated with a solution of permethrin. This increases the effectiveness of the bed net by killing parasitic insects before they are able to find gaps or holes in the net. Personnel working in malaria-endemic areas may be instructed to treat their clothing with permethrin as well.
Permethrin application can cause mild skin irritation and burning.
Permethrin has little systemic absorption, and is considered safe for topical use in adults and children over the age of two months. The FDA has assigned it as pregnancy category B. Animal studies have shown no effects on fertility or teratogenicity, but studies in humans have not been performed. The excretion of permethrin in breastmilk is unknown, and breastfeeding is recommended to be temporarily discontinued during treatment. Skin reactions are uncommon. Excessive exposure to permethrin can cause nausea, headache, muscle weakness, excessive salivation, shortness of breath, and seizures. Worker exposure to the chemical can be monitored by measurement of the urinary metabolites, while severe overdose may be confirmed by measurement of permethrin in serum or blood plasma.
Permethrin does not present any notable genotoxicity or immunotoxicity in humans and farm animals, but is classified by the EPA as a likely human carcinogen when ingested, based on reproducible studies in which mice fed permethrin developed liver and lung tumors. It is known to be highly toxic to fish and aquatic species.
Absorption of topical permethrin is minimal. One in vivo study demonstrated 0.5% absorption in the first 48 hours based upon excretion of urinary metabolites.
Distribution of permethrin has been studied in rat models, with highest amounts accumulating in fat and the brain. This can be explained by the lipophilic nature of the permethrin molecule.
Metabolism of permethrin occurs mainly in the liver, where the molecule undergoes oxidation by the cytochrome P450 system, as well as hydrolysis, into metabolites. Elimination of these metabolites occurs via urinary excretion.
Permethrin has four stereoisomers (two enantiomeric pairs), arising from the two stereocenters in the cyclopropane ring. The trans enantiomeric pair is known as transpermethrin. (1R,3S)-trans and (1R,3R)-cis enantiomers are responsible for the insecticidal properties of permethrin.
Permethrin was first made in 1973.
Numerous synthetic routes exist for the production of the DV-acid ester precursor. The pathway known as the Kuraray Process uses four steps. In general, the final step in the total synthesis of any of the synthetic pyrethroids is a coupling of a DV-acid ester and an alcohol. In the case of permethrin synthesis, the DV-acid cyclopropanecarboxylic acid, 3-(2,2-dichloroethenyl)-2,2-dimethyl-, ethyl ester, is coupled with the alcohol, m-phenoxybenzyl alcohol, through a transesterification reaction with base. Tetraisopropyl titanate or sodium ethylate may be used as the base.
The alcohol precursor may be prepared in three steps. First, m-cresol, chlorobenzene, sodium hydroxide, potassium hydroxide, and copper chloride react to yield m-phenoxytoluene. Second, oxidation of m-phenoxytoluene over selenium dioxide provides m-phenoxybenzaldehyde. Third, a Cannizzaro reaction of the benzaldehyde in formaldehyde and potassium hydroxide affords the m-phenoxybenzyl alcohol.
In Nordic countries and North America, a permethrin formulation for lice treatment is marketed under trade name Nix, available over the counter. Johnson & Johnson's UK brand Lyclear covers an assortment of different products, mostly non-insecticidal, but a few of which are based on permethrin.
Stronger concentrations of permethrin are used to treat scabies (which embed inside the skin), compared to lice (which remain outside the skin). In the U.S. the more concentrated products such as Elimite are available by prescription only.
Permethrin is listed as a "restricted use" substance by the US Environmental Protection Agency (EPA) due to its high toxicity to aquatic organisms, so permethrin and permethrin-contaminated water should be properly disposed of. Permethrin is quite stable, having a half life of 51–71 days in an aqueous environment exposed to light. It is also highly persistent in soil.
Permethrin has little effect on dogs; however, it is toxic to cats. Pesticide-grade permethrin is toxic to cats. Many cats die after being given flea treatments intended for dogs, or by contact with dogs having recently been treated with permethrin. In cats it may induce hyperexcitability, tremors, seizures, and death.
Toxic exposure of permethrin can cause several symptoms, including convulsion, hyperaesthesia, hyperthermia, hypersalivation, and loss of balance and coordination. Exposure to pyrethroid-derived drugs such as permethrin requires treatment by a veterinarian, otherwise the poisoning is often fatal. This intolerance is due to a defect in glucuronosyltransferase, a common detoxification enzyme in other mammals, that also makes the cat intolerant to paracetamol. The use of any external parasiticides based on permethrin is contraindicated for cats (cat ecotoxicology: cutaneous 100 mg/kg – oral 200 mg/kg).[medical citation needed]
Stereochemistry plays a crucial role in determining the toxicological profile of many chiral xenobiotics, e.g. the insecticidal action of mixtures containing the four stereoisomers of permethrin is essentially brought about by the (1R, cis)- and (1R, trans)-forms.