Permethrin

Uses

Permethrin is used:

Medical use

Permethrin is available for topical use as a cream or lotion. It is indicated for the treatment and prevention in exposed individuals of head lice and treatment of scabies.

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.

Pest control

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 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. Military personnel training in malaria-endemic areas may be instructed to treat their uniforms with permethrin, as well.

Permethrin is the most commonly used insecticide worldwide for the protection of wool from keratinophagous insects such as Tineola bisselliella.

Side effects

Permethrin application can cause mild skin irritation and burning. Discontinue use if hypersensitivity occurs.

Safety

Permethrin has little systemic absorption, and is considered safe for topical use in adults and children over the age of 2 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.

According to the Connecticut Department of Public Health, permethrin "has low mammalian toxicity, is poorly absorbed through the skin, and is rapidly inactivated by the body. Skin reactions have been 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, based on reproducible studies in which mice fed permethrin developed liver and lung tumors.

Absorption

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

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

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.

Military use

To better protect soldiers from the risk and annoyance of biting insects, the US and British armies are treating all new uniforms with permethrin.

Stereochemistry

Permethrin has four stereoisomers (two enantiomeric pairs), arising from the two stereocenters in the cyclopropane ring. The trans enantiomeric pair is known as transpermethrin.

History

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.

Brand names

It is marketed by Johnson & Johnson under the name Lyclear. In Nordic countries and North America, it is marketed under trade name Nix, often available over the counter.

Other animals

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. 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.

Domestic animals

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 and many essential oils). The use of any external parasiticides based on permethrin is contraindicated for cats. (Cat ecotoxicology : cutaneous 100 mg/kg - oral 200 mg/kg.)