 Two-dimensional chemical structure of permethrin | |
 Three-dimensional chemical structure of permethrin | |
| Clinical data | |
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| Trade names | Nix, Rid, Elimite, others |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a698037 |
| License data | |
| Routes of administration | Topical |
| ATC code | |
| Legal status | |
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| Pharmacokinetic data | |
| 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 are more sensitive to this toxin.[4] |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.052.771 |
| Chemical and physical data | |
| Formula | C21H20Cl2O3 |
| 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 10−3ppm, 0.2[5] mg/mL (25°C) |
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Permethrin is a medication and aninsecticide.[6][7] As a medication, it is used to treatscabies andlice.[8] It is applied to the skin as a cream or lotion.[6] As an insecticide, it can be sprayed onto outer clothing ormosquito nets to kill the insects that touch them.[7][9]
Side effects include rash and irritation where it isapplied.[8] Use duringpregnancy appears to be safe, and it is approved for use on and around people over the age of two months in the United States.[6] Permethrin is in thepyrethroid family of medications.[6] It works by disrupting the function of theneurons of lice and scabies mites.[6] Permethrin is highly toxic tocats and fish.
Permethrin was discovered in 1972.[10] It is on theWorld Health Organization's List of Essential Medicines.[11] In 2022, it was the 351st most commonly prescribed medication in the United States, with more than 40,000 prescriptions.[12]
Permethrin is available for topical use as a cream or lotion. It isindicated for the treatment and prevention in exposed individuals ofhead lice and treatment ofscabies.[17]In general, one treatment is curative.[18] A single application of permethrin is more effective than a single oral dose of ivermectin for scabies. In addition permethrin provides more rapid symptomatic relief than ivermectin.[19] When a second dose of ivermectin is days later, the efficacy between permethrin and ivermectin approach parity.[20] Contact with eyes should be avoided.[21]
Permethrin acts on the nerve cell membrane to disrupt thesodium channel current by which thepolarization of the membrane is regulated. Delayed repolarization and paralysis of the pests are the consequences of this disturbance.[22][23]
In agriculture, permethrin is mainly used on cotton, wheat,maize, and alfalfa crops. Its use is controversial because, as abroad-spectrum chemical, it kills indiscriminately; as well as the intended pests, it can harm beneficial insects, includinghoney bees, as well as cats and aquatic life.[24][25]
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 kills any immature ticks feeding on the mice.[citation needed]
Permethrin is used in tropical areas to prevent mosquito-borne disease such asdengue fever andmalaria. 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.[citation needed]
Permethrin is the most commonly used insecticide worldwide for the protection of wool from keratinophagous insects such asTineola bisselliella.[26]
To better protect soldiers from the risk and annoyance of biting insects, the British[27] and US armies are treating all new uniforms with permethrin.[28]
Permethrin (as well as other long-term pyrethroids) is effective over several months, in particular when used indoors. International studies report that permethrin can be detected in house dust, in fine dust, and on indoor surfaces even years after the application. Its degradation rate under indoor conditions is approximately 10% after 3 months.[29][30]
InAedes aegypti permethrin resistance is via "knockdown resistance" (kdr) mutations which is common to pyrethroids andDDT. This differs to the most common mechanism ofinsecticide resistance evolution which isselection for preexisting, low-frequencyalleles. García et al. 2009 found that a kdr allele has rapidly spread throughout Mexico and become dominant there.[31]
Permethrin is moderately toxic if ingested, causing abdominal pain, sore throat, nausea and vomiting. If inhaled, permethrin may cause headache, respiratory irritation, difficulty breathing, dizziness, nausea and vomiting. Inhalation is more likely from aerosols than from vapors from surfaces and clothing, as permethrin has a lowvapor pressure and volatilizes slowly.[32]
Topical application of permethrin can cause mild skin irritation, burning andparesthesia.[32] 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 aspregnancy category B. Animal studies have suggested that it may cause endocrine disruption by interfering with estrogenic activity[32] and have shown no effects on fertility orteratogenicity, but studies in humans have not been performed. The excretion of permethrin in breastmilk is unknown, and it is recommended that breastfeeding be temporarily discontinued during treatment.[21] Skin reactions are uncommon.[33]Excessive exposure to permethrin can causenausea, headache, muscle weakness, excessivesalivation, shortness of breath, andseizures. Worker exposure to the chemical can be monitored by measurement of theurinarymetabolites, while severeoverdose may be confirmed by measurement of permethrin inserum orblood plasma.[34]
Permethrin does not present any notablegenotoxicity orimmunotoxicity in humans and farm animals, but is classified by the EPA as a likely humancarcinogen when ingested, based on reproducible studies in which mice fed permethrin developed liver and lungtumors.[35] A 2018 review failed to link permethrin exposure in humans to cancer.[36]
Permethrin is a chemical categorized in the pyrethroid insecticide group.[4] The chemicals in the pyrethroid family are created to emulate the chemicals found in thechrysanthemum flower.[4]
Absorption of topical permethrin is minimal. Onein vivo study demonstrated 0.5% absorption in the first 48 hours based upon excretion of urinary metabolites.[37]
Distribution of permethrin has been studied in rat models, with highest amounts accumulating in fat and the brain.[38] This can be explained by the lipophilic nature of the permethrin molecule.[citation needed]
Metabolism of permethrin occurs mainly in the liver, where the molecule undergoes oxidation by the cytochrome P450 system, as well as hydrolysis, into non-toxic metabolites.[37]
The elimination of permethrin and its metabolites occurs mainly through urinary excretion, but also through feces. In rats, the excretion half-life is 12 hours for plasma and 9 to 23 hours for certain nervous tissue.[32]
Permethrin has fourstereoisomers (twoenantiomeric pairs), arising from the twostereocenters in thecyclopropane ring. Thetrans enantiomeric pair is known as transpermethrin. (1R,3S)-trans and (1R,3R)-cis enantiomers are responsible for the insecticidal properties of permethrin.[39]
-trans-permethrin.svg)
-trans-permethrin.svg)
Permethrin has ahalf-life of about 40 days in soil, 1–3 weeks on the surface of plants, over 20 days indoors, and 19–27 hours in thewater column.[40] Permethrin-contaminated indoor surfaces can be decontaminated with bleach.[41]
In the early 1970s, it was identified that in many pyrethroids, including all naturalpyrethrins and some synthetic analogs developed by that time (such asresmethrin), thefuran ring, being a probable site for photo-sensitized attack by oxygen, was responsible for their instability in air and light. Hence, a group of agricultural chemists at theRothamsted Experimental Station led byMichael Elliott tried to substitute the 5-benzyl-3-furylmethyl alcohol with quite a few structurally similar ones. Discovering that an ester of 3-phenoxybenzyl alcohol with a slightly modified (chlorine-substituted) analog of thechrysanthemic acid they also found earlier was both photo-stable and very toxic for insects, they filed their patent applications in 1972 and published their results inNature in 1973.[10][42]
Numerous synthetic routes exist for the production of the DV-acid ester precursor.[43] The pathway known as the Kuraray Process uses four steps.[44] In general, the final step in thetotal synthesis of any of the syntheticpyrethroids is a coupling of a DV-acid ester and an alcohol. In the case of permethrin synthesis, the DV-acidcyclopropanecarboxylic acid, 3-(2,2-dichloroethenyl)-2,2-dimethyl-, ethyl ester, is coupled with the alcohol,m-phenoxybenzyl alcohol, through atransesterification reaction with base.Tetraisopropyl titanate orsodium ethylate may be used as the base.[44]
The alcohol precursor may be prepared in three steps. First,m-cresol,chlorobenzene,sodium hydroxide,potassium hydroxide, andcuprous chloride react to yieldm-phenoxytoluene.[45] Second, oxidation of m-phenoxytoluene overselenium dioxide providesm-phenoxybenzaldehyde. Third, aCannizzaro reaction of thebenzaldehyde informaldehyde and potassium hydroxide affords the m-phenoxybenzyl alcohol.[44]
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.[46]
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.[3][47]
It is known to be highly toxic to cats, fish and aquatic species with long-lasting effects.[4][48]
Permethrin is toxic to cats; however, it has little effect on dogs.[4][49][50] Many cats die after being given flea treatments intended for dogs, or by contact with dogs having recently been treated with permethrin.[51] In cats it may induce hyperexcitability, tremors, seizures, and death.[52]
Toxic exposure of permethrin can cause several symptoms, includingconvulsion,hyperaesthesia,hyperthermia,hypersalivation, and loss of balance and coordination. Exposure topyrethroid-derived drugs such as permethrin requires treatment by a veterinarian, otherwise the poisoning is often fatal.[53][54] This intolerance is due to a defect inglucuronosyltransferase, a common detoxification enzyme in other mammals, that also makes the cat intolerant toparacetamol (acetaminophen).[55] Based on those observations, the use of any external parasiticides based on permethrin is contraindicated for cats.
Permethrin is listed as a "restricted use" substance by the USEnvironmental Protection Agency (EPA)[56] due to its high toxicity to aquatic organisms,[57] 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.[58]
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.
Human lice and pediculosis | ||
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| Other terms of interest | ||
