View source for Permethrin

{{Short description|Medication and insecticide}}
{{Use dmy dates|date=March 2024}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Infobox drug
| image             = Permethrin-2D-skeletal.png
| image_class       = skin-invert-image
| alt               =
| caption           = Two-dimensional chemical structure of permethrin
| image2             = Permethrin MT 20200909.png
| image_class2       = bg-transparent
| alt2               =
| caption2           = Three-dimensional chemical structure of permethrin

<!-- Clinical data -->
| pronounce         = 
| tradename         = Nix, Rid, Elimite, others
| Drugs.com         = {{Drugs.com|monograph|permethrin}}
| MedlinePlus       = a698037
| DailyMedID        = Permethrin
| pregnancy_AU      = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_AU_comment = 
| pregnancy_category=
| routes_of_administration = [[topical administration|Topical]]
| class             = 
| ATC_prefix        = P03
| ATC_suffix        = AC04
| ATC_supplemental  = {{ATCvet|P53|AC04}}

<!-- Legal status -->
| legal_AU          = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->
| legal_AU_comment  = 
| legal_BR          = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C5, D1, D2, E, F1, F2, F3, F4 -->
| legal_BR_comment  = 
| legal_CA          = OTC
| legal_CA_comment  = <ref>{{cite web |title=Nix Product Information |url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=37239 |website=[[Health Canada]]|access-date=19 June 2024}}</ref>
| legal_DE          = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment  = 
| legal_NZ          = <!-- Class A, B, C -->
| legal_NZ_comment  = 
| legal_UK = OTC 
| legal_UK_comment = (1%), Rx (5%)
| legal_US = OTC 
| legal_US_comment = (1% [[pediculicide]]),<ref>{{cite web | title=Good Sense Lice Killing Creme Rinse- permethrin lotion | website=DailyMed | date=21 November 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=056fb377-34dd-4d33-83d7-c895b105f574 | access-date=29 December 2024}}</ref> Rx (5% [[scabicide]])<ref name="Elimite FDA label">{{cite web | title=Elimite- permethrin cream | website=DailyMed | date=24 January 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=443c0446-ccba-4f52-83ed-4c3163f35807 | access-date=29 December 2024}}</ref>
| legal_EU          = 
| legal_EU_comment  = 
| legal_UN          = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment  = 
| legal_status      = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->
| bioavailability   =
| protein_bound     =
| 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.<ref name=PermGen/>
| metabolites       =
| onset             =
| elimination_half-life =
| duration_of_action =
| excretion         =

<!-- Identifiers -->
| CAS_number        = 52645-53-1
| CAS_supplemental  = {{cascite|correct|CAS}}
| PubChem           = 40326
| IUPHAR_ligand     =
| DrugBank          = DB04930
| ChemSpiderID      = 36845
| UNII              = 509F88P9SZ
| KEGG              = C14388
| ChEBI             = 34911
| ChEMBL            = 1525
| NIAID_ChemDB      =
| PDB_ligand        = 
| synonyms          =

<!-- Chemical and physical data -->
| IUPAC_name        = (±)-3-Phenoxybenzyl 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate
| C=21
| H=20
| Cl=2
| O=3
| SMILES            = Cl/C(Cl)=C/C3C(C(=O)OCc2cccc(Oc1ccccc1)c2)C3(C)C
| StdInChI          = 1S/C21H20Cl2O3/c1-21(2)17(12-18(22)23)19(21)20(24)25-13-14-7-6-10-16(11-14)26-15-8-4-3-5-9-15/h3-12,17,19H,13H2,1-2H3
| StdInChI_comment  =
| StdInChIKey       = RLLPVAHGXHCWKJ-UHFFFAOYSA-N
| density           = 1.19 g/cm<sup>3</sup>, solid
| density_notes     =
| melting_point     = 34
| melting_high      =
| melting_notes     =
| boiling_point     = 200
| boiling_notes     =
| solubility        = 5.5 x 10<sup>−3</sup> [[Parts per million|ppm]], 0.2 <ref>{{cite journal | vauthors = Metcalf RL, Horowitz AR |title=Insect Control, 2. Individual Insecticides |journal=Ullmann's Encyclopedia of Industrial Chemistry |date=19 November 2014 |pages=1–94 |doi=10.1002/14356007.s14_s01 |isbn=978-3-527-30673-2 }}</ref>
| sol_units  = &nbsp;mg/mL (25°C)
| specific_rotation =
}}

<!-- Definition and uses -->
'''Permethrin''' is a medication and an [[insecticide]].<ref name=AHFS2016 /><ref name=Key2013>{{cite book| vauthors = Keystone JS, Kozarsky PE, Freedman DO, Connor BA |title=Travel Medicine|date=2013|publisher=Elsevier Health Sciences|isbn=978-1-4557-1076-8|page=58|url=https://books.google.com/books?id=hSf30j2YFSMC&pg=PA58|language=en|url-status=live|archive-url=https://web.archive.org/web/20161220155051/https://books.google.ca/books?id=hSf30j2YFSMC&pg=PA58|archive-date=20 December 2016}}</ref> As a medication, it is used to treat [[scabies]] and [[lice]].<ref name=WHO2008>{{cite book | title = WHO Model Formulary 2008 | year = 2009 | isbn = 978-92-4-154765-9 | vauthors = ((World Health Organization)) | veditors = Stuart MC, Kouimtzi M, Hill SR | hdl = 10665/44053 | author-link = World Health Organization | publisher = World Health Organization | page = 213 }}</ref> It is applied to the skin as a cream or lotion.<ref name=AHFS2016>{{cite web|title=Permethrin|url=https://www.drugs.com/monograph/permethrin.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161221013040/https://www.drugs.com/monograph/permethrin.html|archive-date=21 December 2016}}</ref> As an insecticide, it can be sprayed onto outer clothing or [[mosquito nets]] to kill the insects that touch them.<ref name=Key2013 /><ref name="usepa">{{cite web |title=Repellent-Treated Clothing |date=15 July 2013 |url=https://www.epa.gov/insect-repellents/repellent-treated-clothing |publisher=United States Environmental Protection Agency |access-date=28 May 2023}}</ref>

<!-- Side effects and mechanism -->
Side effects include rash and irritation where it is [[Topical medication|applied]].<ref name=WHO2008 /> Use during [[pregnancy]] appears to be safe, and it is approved for use on and around people over the age of two months in the United States.<ref name=AHFS2016 /> Permethrin is in the [[pyrethroid]] family of medications.<ref name=AHFS2016 /> It works by disrupting the function of the [[neuron]]s of lice and scabies mites.<ref name=AHFS2016 /> Permethrin is highly toxic to [[cat]]s and fish.

<!-- Society and culture -->
Permethrin was discovered in 1972.<ref name=":0" /> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref> In 2022, it was the 351st most commonly prescribed medication in the United States, with more than 40,000 prescriptions.<ref>{{cite web | title = Permethrin Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Permethrin | access-date = 30 August 2024 }}</ref>

== Uses ==
=== Insecticide ===
* In agriculture, to protect crops (a drawback is that it is lethal to bees)
* In agriculture, to kill livestock parasites
* For industrial and domestic insect control
* In the textile industry, to prevent insect attack of woollen products
* In aviation, the [[WHO]], [[International Health Regulations|IHR]] and [[ICAO]] require arriving aircraft be [[Aircraft disinsection|disinsected]] prior to embarkation, departure, descent, or deplaning in certain countries. Aircraft disinsection with permethrin-based products is recommended only prior to embarkation. Prior to departure (after boarding), at the top of descent or on arrival, d-phenothrin-based (1R-trans phenothrin) aircraft insecticides are recommended.
[[File:Permethrin 0.5%.png|thumb|0.5% permethrin powder]]

=== Insect incapacitation ===
* As a personal protective measure, 0.5% permethrin is applied to outer clothing. It is a cloth impregnant, notably in mosquito nets and field wear. While permethrin may be marketed as an insect repellent, it does not prevent insects from landing. Instead it works by incapacitating or killing insects on contact before they can bite. In 2016, Consumer Reports found that, as consecutive washes reduce permethrin concentration, incapacitation becomes too slow to prevent bites. In these cases, other common topical [[Insect repellent|repellents]] such as [[icaridin]] may be applied to the clothing, though some, such as [[DEET]] and [[Ethyl butylacetylaminopropionate|IR3535]], can damage certain synthetic fabrics.<ref>{{cite web | vauthors = Jeneen I |title=Can Permethrin Treated Clothing Help You Avoid Mosquito Bites? |url=https://www.consumerreports.org/insect-repellents/permethrin-treated-clothing-mosquito-bites/ |website=Consumer Reports |date=26 May 2016 |access-date=31 May 2019 |archive-date=31 May 2019 |archive-url=https://web.archive.org/web/20190531050608/https://www.consumerreports.org/insect-repellents/permethrin-treated-clothing-mosquito-bites/ |url-status=live }}</ref><ref name="usepa"/><ref>{{cite web |title=How to Use Permethrin on Clothing, Safely |url=https://www.consumerreports.org/health/insect-repellent/how-to-use-permethrin-on-clothing-safely-a4370607226/ |publisher=Consumer Reports |access-date=29 May 2023 |archive-date=6 May 2023 |archive-url=https://web.archive.org/web/20230506205018/https://www.consumerreports.org/health/insect-repellent/how-to-use-permethrin-on-clothing-safely-a4370607226/ |url-status=live }}</ref><ref>{{cite web |title=How to Use Permethrin |date=18 March 2020 |url=https://www.cdc.gov/mosquitoes/prevention/about-permethrin-treated-clothing-and-gear.html |publisher=U.S. [[Centers for Disease Control and Prevention]] (CDC) |access-date=11 September 2023}}</ref>
* In pet flea preventive collars or treatment (safe for use on dogs but not cats<ref>{{cite journal | vauthors = Malik R, Ward MP, Seavers A, Fawcett A, Bell E, Govendir M, Page S | title = Permethrin spot-on intoxication of cats Literature review and survey of veterinary practitioners in Australia | journal = Journal of Feline Medicine and Surgery | volume = 12 | issue = 1 | pages = 5–14 | date = January 2010 | pmid = 20123482 | doi = 10.1016/j.jfms.2009.12.002 | s2cid = 1234198 | pmc = 10845477 }}</ref>)
* In timber treatment

=== 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]].<ref>{{cite web|title=Permethrin (Lexi-Drugs)|url=http://www.lexi.com/|work=Lexicomp Online|publisher=Wolters Kluwer|access-date=19 April 2014|url-status=live|archive-url=https://web.archive.org/web/20140417164854/http://www.lexi.com/|archive-date=17 April 2014}}</ref>
In general, one treatment is curative.<ref>{{cite web|title=Permethrin Patient Package Insert|url=https://www.accessdata.fda.gov/drugsatfda_docs/anda/98/074806ap.pdf|publisher=FDA|access-date=19 April 2014|url-status=live|archive-url=https://web.archive.org/web/20140420043409/http://www.accessdata.fda.gov/drugsatfda_docs/anda/98/074806ap.pdf|archive-date=20 April 2014}}</ref> 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.<ref>{{cite journal | vauthors = Usha V, Gopalakrishnan Nair TV | title = A comparative study of oral ivermectin and topical permethrin cream in the treatment of scabies | journal = Journal of the American Academy of Dermatology | volume = 42 | issue = 2 Pt 1 | pages = 236–240 | date = February 2000 | pmid = 10642678 | doi = 10.1016/S0190-9622(00)90131-2 | publication-date = Feb 2000 }}</ref> When a second dose of ivermectin is days later, the efficacy between permethrin and ivermectin approach parity.<ref>{{cite journal | vauthors = Dhana A, Yen H, Okhovat JP, Cho E, Keum N, Khumalo NP | title = Ivermectin versus permethrin in the treatment of scabies: A systematic review and meta-analysis of randomized controlled trials | journal = Journal of the American Academy of Dermatology | volume = 78 | issue = 1 | pages = 194–198 | date = January 2018 | pmid = 29241784 | doi = 10.1016/j.jaad.2017.09.006 | s2cid = 29398956 | doi-access = free | publication-date = Jan 2018 }}</ref>  Contact with eyes should be avoided.<ref name="Package Label">{{cite web|title=Package Label|url=https://www.accessdata.fda.gov/drugsatfda_docs/anda/2000/75014_Permethrin_Prntlbl.pdf|publisher=Alpharma, USPD, Inc. Baltimore|access-date=19 April 2014|url-status=live|archive-url=https://web.archive.org/web/20140420031625/http://www.accessdata.fda.gov/drugsatfda_docs/anda/2000/75014_Permethrin_Prntlbl.pdf|archive-date=20 April 2014}}</ref>

==== Mechanism of action ====
Permethrin acts on the nerve cell membrane to disrupt the [[sodium channel]] current by which the [[Action potential|polarization]] of the membrane is regulated. Delayed repolarization and paralysis of the pests are the consequences of this disturbance.<ref>{{cite web |title=MarkerDB |url=https://markerdb.ca/conditions/6982 |access-date=2 January 2024 |website=markerdb.ca |archive-date=2 January 2024 |archive-url=https://web.archive.org/web/20240102133744/https://markerdb.ca/conditions/6982 |url-status=live }}</ref><ref>{{cite web |title=Permethrin Cream, 5%* |url=https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=041444b6-a71e-4d13-8d24-f2d104bf721d&type=display |access-date=2 January 2024 |website=dailymed.nlm.nih.gov}}</ref>

=== Pest control / effectiveness and persistence ===
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 bee]]s, as well as cats and aquatic life.<ref>{{cite journal | vauthors = Ian RH | title = Aquatic organisms and pyrethroids | year = 1989 | journal = [[Pesticide Science]] | volume = 27 | issue = 4 | pages = 429–457 | doi = 10.1002/ps.2780270408}}</ref><ref>{{cite journal | vauthors = Drago B, Shah NS, Shah SH | title = Acute permethrin neurotoxicity: Variable presentations, high index of suspicion | journal = Toxicology Reports | volume = 1 | pages = 1026–1028 | date = 2014 | pmid = 28962315 | pmc = 5598406 | doi = 10.1016/j.toxrep.2014.09.007 | bibcode = 2014ToxR....1.1026D }}</ref>

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|date=December 2022}}

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.{{citation needed|date=February 2023}}

Permethrin is the most commonly used insecticide worldwide for the protection of wool from keratinophagous insects such as ''[[Tineola bisselliella]]''.<ref>{{cite journal | vauthors = Ingham PE, McNeil SJ, Sunderland MR | year = 2012 | title = Functional finishes for wool – Eco considerations | journal = Advanced Materials Research | volume = 441 | pages = 33–43 | doi = 10.4028/www.scientific.net/amr.441.33| s2cid = 136607213 }}</ref>

To better protect soldiers from the risk and annoyance of biting insects, the British<ref>{{cite web | url = http://www.army.mod.uk/documents/general/Black_Bag_A5_booklet.pdf | work = Personal Clothing – British Army Website | archive-url = https://web.archive.org/web/20150923185556/http://www.army.mod.uk/documents/general/Black_Bag_A5_booklet.pdf | archive-date=23 September 2015 | title = What's in the Black Bag? | access-date = 14 October 2015 }}</ref> and US armies are treating all new uniforms with permethrin.<ref>{{cite web | url = https://www.army.mil/article/88171/Army_s_new_ACUs_combat_insect_borne_diseases/ | title = Insect-repelling ACUs now available to all Soldiers | archive-url = https://web.archive.org/web/20131004213322/http://www.army.mil/article/88171/Army_s_new_ACUs_combat_insect_borne_diseases/ | archive-date = 4 October 2013| work = Canadian and United States Army | url-status = live | date = October 2012 }}</ref>

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.<ref>{{cite journal | vauthors = Nakagawa LE, do Nascimento CM, Costa AR, Polatto R, Papini S | title = Persistence of indoor permethrin and estimation of dermal and non-dietary exposure | journal = Journal of Exposure Science & Environmental Epidemiology | volume = 30 | issue = 3 | pages = 547–553 | date = May 2020 | pmid = 30926895 | doi = 10.1038/s41370-019-0132-7 | bibcode = 2020JESEE..30..547N | s2cid = 85566713 }}</ref><ref>{{cite journal | vauthors = Berger-Preiess E, Preiess A, Sielaff K, Raabe M, Ilgen B, Levsen K |doi=10.1111/j.1600-0668.1997.00004.x|title=The Behaviour of Pyrethroids Indoors: A Model Study|year=1997 |journal=Indoor Air|volume=7|issue=4|pages=248–262|bibcode=1997InAir...7..248B |doi-access=free}}</ref>

=== Resistance ===
In ''[[Aedes aegypti]]'' permethrin resistance is via "[[knockdown resistance]]" (kdr) mutations which is common to pyrethroids and [[DDT]]. This differs to the most common mechanism of [[insecticide resistance]] evolution which is [[selection (genetics)|selection]] for preexisting, low-frequency [[allele]]s. García et al. 2009 found that a kdr allele has rapidly spread throughout Mexico and become dominant there.<ref name="Labbe-et-al-2011">{{cite book | vauthors = Labbé P, Alout H, Djogbénou L, Pasteur N, Weill M | veditors = Tibayrenc M | title=Genetics and Evolution of Infectious Disease | chapter=Evolution of Resistance to Insecticide in Disease Vectors | publisher=[[Elsevier]] | year=2011 | isbn=978-0-12-384890-1 | pages=363–409}}</ref>

== Adverse effects ==
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 low [[vapor pressure]] and volatilizes slowly.<ref name="npic">{{cite web |title=Permethrin |url=http://npic.orst.edu/factsheets/archive/Permtech.html |publisher=National Pesticide Information Center |access-date=30 August 2023}}</ref>

Topical application of permethrin can cause mild skin irritation, burning and [[paresthesia]].<ref name="npic"/> 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 suggested that it may cause endocrine disruption by interfering with estrogenic activity<ref name="npic"/> and have shown no effects on fertility or [[Teratology|teratogenicity]], 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.<ref name="Package Label" /> Skin reactions are uncommon.<ref>{{cite web | url = http://www.dph.state.ct.us/BCH/infectiousdise/tickborne/tick.htm#Permethrin | title = Tick Bite Prevention | vauthors = Stafford III KC | date = February 1999 | publisher = Connecticut Department of Public Health | url-status = dead | archive-url = https://web.archive.org/web/20050912070432/http://www.dph.state.ct.us/BCH/infectiousdise/tickborne/tick.htm#Permethrin | archive-date = 12 September 2005}}</ref>
Excessive exposure to permethrin can cause [[nausea]], headache, muscle weakness, excessive [[salivation]], shortness of breath, and [[seizure]]s. Worker exposure to the chemical can be monitored by measurement of the [[urinary]] [[metabolite]]s, while severe [[Drug overdose|overdose]] may be confirmed by measurement of permethrin in [[Blood serum|serum]] or [[blood plasma]].<ref>{{cite book | vauthors = Baselt R | title = Disposition of Toxic Drugs and Chemicals in Man | edition = 8th | publisher = Biomedical Publications | location = Foster City, CA | date = 2008 | pages = 1215–1216 }}</ref>

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 [[tumor]]s.<ref>{{cite report | title = Permethrin Facts | url = https://nepis.epa.gov/Exe/ZyNET.exe/P1005J0O.txt?ZyActionD=ZyDocument&Client=EPA&Index=2006%20Thru%202010&Docs=&Query=Permethrin&Time=&EndTime=&SearchMethod=2&TocRestrict=n&Toc=&TocEntry=&QField=&QFieldYear=&QFieldMonth=&QFieldDay=&UseQField=&IntQFieldOp=0&ExtQFieldOp=0&XmlQuery=&File=D%3A%5CZYFILES%5CINDEX%20DATA%5C06THRU10%5CTXT%5C00000012%5CP1005J0O.txt&User=ANONYMOUS&Password=anonymous&SortMethod=h%7C-&MaximumDocuments=15&FuzzyDegree=0&ImageQuality=r85g16/r85g16/x150y150g16/i500&Display=hpfr&DefSeekPage=x&SearchBack=ZyActionL&Back=ZyActionS&BackDesc=Results%20page&MaximumPages=1&ZyEntry=1&SeekPage=x | work = National Service Center for Environmental Publications (NSCEP) | publisher = U.S. Environmental Protection Agency | date = June 2006 | access-date = 24 March 2023 | archive-date = 24 March 2023 | archive-url = https://web.archive.org/web/20230324192313/https://nepis.epa.gov/Exe/ZyNET.exe/P1005J0O.txt?ZyActionD=ZyDocument&Client=EPA&Index=2006%20Thru%202010&Docs=&Query=Permethrin&Time=&EndTime=&SearchMethod=2&TocRestrict=n&Toc=&TocEntry=&QField=&QFieldYear=&QFieldMonth=&QFieldDay=&UseQField=&IntQFieldOp=0&ExtQFieldOp=0&XmlQuery=&File=D%3A%5CZYFILES%5CINDEX%20DATA%5C06THRU10%5CTXT%5C00000012%5CP1005J0O.txt&User=ANONYMOUS&Password=anonymous&SortMethod=h%7C-&MaximumDocuments=15&FuzzyDegree=0&ImageQuality=r85g16%2Fr85g16%2Fx150y150g16%2Fi500&Display=hpfr&DefSeekPage=x&SearchBack=ZyActionL&Back=ZyActionS&BackDesc=Results%20page&MaximumPages=1&ZyEntry=1&SeekPage=x | url-status = live }}</ref> A 2018 review failed to link permethrin exposure in humans to cancer.<ref>{{cite journal | vauthors = Boffetta P, Desai V | title = Exposure to permethrin and cancer risk: a systematic review | journal = Critical Reviews in Toxicology | volume = 48 | issue = 6 | pages = 433–442 | date = July 2018 | pmid = 29687728 | doi = 10.1080/10408444.2018.1439449 | s2cid = 26073529 }}</ref>

== Pharmacokinetics ==

Permethrin is a chemical categorized in the pyrethroid insecticide group.<ref name=PermGen/> The chemicals in the pyrethroid family are created to emulate the chemicals found in the [[chrysanthemum]] flower.<ref name=PermGen/>

=== 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.<ref name="van der Rhee 1989 170–3">{{cite journal | vauthors = van der Rhee HJ, Farquhar JA, Vermeulen NP | title = Efficacy and transdermal absorption of permethrin in scabies patients | journal = Acta Dermato-Venereologica | volume = 69 | issue = 2 | pages = 170–173 | date = 1989 | pmid = 2564238 }}</ref>

=== Distribution ===
Distribution of permethrin has been studied in rat models, with highest amounts accumulating in fat and the brain.<ref>{{cite journal |vauthors=Tornero-Velez R, Davis J, Scollon EJ, Starr JM, Setzer RW, Goldsmith MR, Chang DT, Xue J, Zartarian V, DeVito MJ, Hughes MF |date=November 2012 |title=A pharmacokinetic model of cis- and trans-permethrin disposition in rats and humans with aggregate exposure application |journal=Toxicological Sciences |publisher=[[Oxford University Press]] |publication-date=2012-08-01 |volume=130 |issue=1 |pages=33–47 |doi=10.1093/toxsci/kfs236 |pmid=22859315 |s2cid=20980566 |via=Silverchair}}</ref> This can be explained by the lipophilic nature of the permethrin molecule.{{citation needed|date=December 2022}}

=== Metabolism ===
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.<ref name="van der Rhee 1989 170–3" />

=== Excretion ===
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.<ref name="npic"/>

== Stereochemistry ==
Permethrin has four [[Stereoisomerism|stereoisomers]] (two [[enantiomer]]ic pairs), arising from the two [[stereocenter]]s in the [[cyclopropane]] ring. The ''[[Cis-trans isomerism|trans]]'' enantiomeric pair is known as transpermethrin. (1''R'',3''S'')-''trans'' and (1''R'',3''R'')-''cis'' enantiomers are responsible for the insecticidal properties of permethrin.<ref>{{cite journal | vauthors = Dornetshuber J, Bicker W, Lämmerhofer M, Lindner W, Karwan A, Bursch W |title=Impact of stereochemistry on biological effects of permethrin: induction of apoptosis in human hepatoma cells (HCC-1.2) and primary rat hepatocyte cultures |journal=BMC Pharmacology |date=14 November 2007 |volume=7 |issue=Supplement 2 |article-number=A65 |doi=10.1186/1471-2210-7-S2-A65 |issn=1471-2210 |quote=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.|doi-access=free }}</ref>

<div class="skin-invert-image"><gallery widths="240" heights="80" perrow="2">
(1S)-trans-permethrin.svg|(1''S'',3''R'')-''trans'' enantiomer
(3S)-trans-permethrin.svg|(1''R'',3''S'')-''trans'' enantiomer
Cis-permethrin-A.svg|(1''S'',3''S'')-''cis'' enantiomer
Cis-permethrin-B.svg|(1''R'',3''R'')-''cis'' enantiomer
</gallery></div>

== Environment ==
Permethrin has a [[half-life]] of about 40 days in soil, 1–3 weeks on the surface of plants, over 20 days indoors, and 19–27 hours in the [[water column]].<ref>{{cite web |title=Pesticide Half-life |url=http://npic.orst.edu/factsheets/half-life.html |publisher=National Pesticide Information Center |access-date=11 September 2023 |date=May 2015}}</ref> Permethrin-contaminated indoor surfaces can be decontaminated with bleach.<ref>{{cite journal | vauthors = Oudejans L, Mysz A, Gibb Snyder E, Wyrzykowska-Ceradini B, Nardin J, Tabor D, Starr J, Stout D, Lemieux P | title = Remediating Indoor Pesticide Contamination from Improper Pest Control Treatments: Persistence and Decontamination Studies | journal = Journal of Hazardous Materials | volume = 397 | article-number = 122743 | date = October 2020 | pmid = 32361138 | pmc = 7472880 | doi = 10.1016/j.jhazmat.2020.122743 | bibcode = 2020JHzM..39722743O }}</ref>

== History ==
In the early 1970s, it was identified that in many pyrethroids, including all natural [[pyrethrin]]s and some synthetic analogs developed by that time (such as [[resmethrin]]), the [[furan]] 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 the [[Rothamsted Experimental Station]] led by [[Michael Elliott (chemist)|Michael 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 the [[chrysanthemic 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 in [[Nature (journal)|Nature]] in 1973.<ref name=":0">{{cite journal | vauthors = Elliott M, Farnham AW, Janes NF, Needham PH, Pulman DA, Stevenson JH | title = A photostable pyrethroid | journal = Nature | volume = 246 | issue = 5429 | pages = 169–170 | date = November 1973 | pmid = 4586114 | doi = 10.1038/246169a0 | s2cid = 4176154 | bibcode = 1973Natur.246..169E }}</ref><ref>{{Cite patent|country=GB|number=1413491|title=3-SUBSTITUTED-2,2-DIMETHYL-CYCLOPROPANE CARBOXYLIC ACID ESTERS THEIR PREPARATION AND THEIR USE IN PESTICIDAL COMPOSITIONS|pubdate=1973-04-30|gdate=1975-11-12|invent1=Elliott|invent2=James|invent3=Pulman|inventor1-first=Michael|inventor2-first=Norman Frank|inventor3-first=David Allen|assign1=National Research Development Corporation}}</ref>

Numerous synthetic routes exist for the production of the DV-acid ester precursor.<ref>DV-acid = 3-(2,2-'''D'''ichloro'''v'''inyl)-2,2-dimethylcyclopropanecarboxylic acid</ref> The pathway known as the Kuraray Process uses four steps.<ref name="Leonard A. Wasselle 1981" /> In general, the final step in the [[total synthesis]] of any of the synthetic [[pyrethroid]]s 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.<ref name="Leonard A. Wasselle 1981">{{cite web | vauthors = Wasselle LA | title = Pyrethroid Insecticides | url = https://www.spglobal.com/pdf/RP143_toc_173236110917062932.pdf | work = SRI International Report #143 | location = Menlo Park, CA | date = June 1981 | access-date = 17 September 2023 | archive-date = 16 March 2024 | archive-url = https://web.archive.org/web/20240316192334/https://www.spglobal.com/pdf/RP143_toc_173236110917062932.pdf | url-status = live }}</ref>

The alcohol precursor may be prepared in three steps. First, [[m-cresol]], [[chlorobenzene]], [[sodium hydroxide]], [[potassium hydroxide]], and [[cuprous chloride]] react to yield [[m-phenoxytoluene]].<ref>{{cite patent |inventor=Colby, Thomas H. |country=US |number=4229594A |pubdate=1980-10-21 |title=Preparation of meta-phenoxytoluene}}</ref> 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.<ref name="Leonard A. Wasselle 1981" />

== Brand names ==
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.<ref>{{cite web|url=https://www.lyclear.co.uk/products/head-lice-treatments/|website=Lyclear UK|title=Head Lice Treatments|access-date=24 September 2018|archive-date=25 September 2018|archive-url=https://web.archive.org/web/20180925025411/https://www.lyclear.co.uk/products/head-lice-treatments/|url-status=live}}</ref>

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.<ref name="Elimite FDA label" /><ref>{{cite web|url=https://www.cdc.gov/scabies/hcp/clinical-care/ |website=U.S. [[Centers for Disease Control and Prevention]] (CDC) |title=Resources for Health Professionals: Scabies Medications|date=19 April 2019|access-date=24 September 2018|archive-date=30 April 2015|archive-url=https://web.archive.org/web/20150430075605/http://www.cdc.gov/parasites/scabies/health_professionals/meds.html|url-status=live}}</ref>

==Other animals==
It is known to be highly toxic to cats, fish and aquatic species with long-lasting effects.<ref name=PermGen>{{cite web|url=http://npic.orst.edu/factsheets/PermGen.html#wildlife |title=Permethrin General Fact Sheet|website=npic.orst.edu|language=en|access-date=6 January 2018|archive-date=3 January 2018|archive-url=https://web.archive.org/web/20180103154911/http://npic.orst.edu/factsheets/PermGen.html#wildlife|url-status=dead}}</ref><ref>{{cite web |title=Permethrin |url=https://pubchem.ncbi.nlm.nih.gov/compound/Permethrin#section=GHS-Classification |website=pubchem.ncbi.nlm.nih.gov |publisher=PubChem |access-date=28 June 2020 |language=en |archive-date=28 June 2020 |archive-url=https://web.archive.org/web/20200628162254/https://pubchem.ncbi.nlm.nih.gov/compound/Permethrin#section=GHS-Classification |url-status=live }}</ref>

=== Cats ===
Permethrin is toxic to cats; however, it has little effect on dogs.<ref name=PermGen/><ref>{{cite web |url=https://www.consumerreports.org/pets/should-you-use-natural-tick-prevention-for-your-dog-or-cat/ |title=Should You Use Natural Tick Prevention for Your Dog or Cat? | vauthors = Roberts C |date=22 October 2018 |website=Consumer Reports |publisher=Consumer Reports Inc. |access-date=12 December 2018 |archive-date=15 December 2018 |archive-url=https://web.archive.org/web/20181215223121/https://www.consumerreports.org/pets/should-you-use-natural-tick-prevention-for-your-dog-or-cat/ |url-status=live }}</ref><ref>{{cite book | vauthors = Englar RE |title=Common Clinical Presentations in Dogs and Cats |date=2019 |publisher=John Wiley & Sons |isbn=978-1-119-41459-9 |page=333 |url=https://books.google.com/books?id=KNKgDwAAQBAJ&pg=PA333 |language=en |access-date=31 May 2020 |archive-date=19 August 2020 |archive-url=https://web.archive.org/web/20200819135524/https://books.google.com/books?id=KNKgDwAAQBAJ&pg=PA333 |url-status=live }}</ref> Many cats die after being given flea treatments intended for dogs, or by contact with dogs having recently been treated with permethrin.<ref>{{cite journal | vauthors = Linnett PJ | title = Permethrin toxicosis in cats | journal = Australian Veterinary Journal | volume = 86 | issue = 1–2 | pages = 32–35 | year = 2008 | pmid = 18271821 | doi = 10.1111/j.1751-0813.2007.00198.x }}</ref> In cats it may induce hyperexcitability, tremors, seizures, and death.<ref name="MaddisonPage2008">{{cite book| vauthors = Page SW | veditors = Maddison JE |others=Stephen W. Page, David Church|title=Small Animal Clinical Pharmacology|chapter-url=https://books.google.com/books?id=RpsROVqemk8C&pg=PA236|year=2008|publisher=Elsevier Health Sciences|isbn=978-0-7020-2858-8|page=236|chapter=10: Antiparasitic drugs|url-status=live|archive-url=https://web.archive.org/web/20170324014840/https://books.google.com/books?id=RpsROVqemk8C&pg=PA236|archive-date=24 March 2017}}</ref>

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.<ref>{{cite journal | vauthors = Richardson JA | title = Permethrin spot-on toxicoses in cats. | journal = Journal of Veterinary Emergency and Critical Care | date = June 2000 | volume = 10 | issue = 2 | pages = 103–106 | doi = 10.1111/j.1476-4431.2000.tb00006.x }}</ref><ref>{{cite journal | vauthors = Dymond NL, Swift IM | title = Permethrin toxicity in cats: a retrospective study of 20 cases | journal = Australian Veterinary Journal | volume = 86 | issue = 6 | pages = 219–223 | date = June 2008 | pmid = 18498556 | doi = 10.1111/j.1751-0813.2008.00298.x }}</ref> This intolerance is due to a defect in [[glucuronosyltransferase]], a common detoxification enzyme in other mammals, that also makes the cat intolerant to [[paracetamol]] (acetaminophen).<ref>{{cite journal | vauthors = Bordeau W | date = January 2009 | journal = Sciences & Pratique | volume = 1018 |url=http://www.depecheveterinaire.com/basedocudv/actualites_dermatologiques_etude_retrospective_australienne_signes_nerveux_digestifs.pdf |title=Intoxications du chat par la perméthrine: rares mais graves |access-date=26 January 2015 |url-status=dead |archive-url=https://web.archive.org/web/20131227010357/http://www.depecheveterinaire.com/basedocudv/actualites_dermatologiques_etude_retrospective_australienne_signes_nerveux_digestifs.pdf |archive-date=27 December 2013}}</ref> Based on those observations, the use of any external parasiticides based on permethrin is contraindicated for cats.

=== Aquatic organisms ===
Permethrin is listed as a "restricted use" substance by the US [[United States Environmental Protection Agency|Environmental Protection Agency]] (EPA)<ref name=rupr>{{cite web | title =Restricted Use Products (RUP) Report | url =https://www.epa.gov/pesticide-worker-safety/restricted-use-products-rup-report | date=16 February 2024 | publisher=U.S. [[United States Environmental Protection Agency|Environmental Protection Agency]] (EPA) | access-date =1 December 2009| url-status =live| archive-url =https://web.archive.org/web/20100111030314/http://www.epa.gov/opprd001/rup/rup6mols.htm| archive-date =11 January 2010}}</ref> due to its high toxicity to aquatic organisms,<ref name=RED>{{cite web| author = Environmental Protection Agency| author-link = United States Environmental Protection Agency| title =Permethrin Facts (Reregistration Eligibility Decision (RED) Fact Sheet)| url =https://www3.epa.gov/pesticides/chem_search/reg_actions/reregistration/fs_PC-109701_1-Jun-06.pdf| date =June 2006| website =epa.gov| publisher =EPA Special Review and Reregistration Division| access-date =13 May 2020| archive-date =6 August 2020| archive-url =https://web.archive.org/web/20200806094905/https://www3.epa.gov/pesticides/chem_search/reg_actions/reregistration/fs_PC-109701_1-Jun-06.pdf| url-status =live}}</ref> 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.<ref>{{cite web | vauthors = Imgrund H | date = 28 January 2003 | publisher = Environmental Monitoring Branch, California Department of Pesticide Regulation, California Environmental Protection Agency | url = http://www.cdpr.ca.gov/docs/emon/pubs/fatememo/permethrin.pdf | title = Environmental Fate of Permethrin | url-status = live | archive-url = https://web.archive.org/web/20131007224634/http://www.cdpr.ca.gov/docs/emon/pubs/fatememo/permethrin.pdf | archive-date = 7 October 2013}}</ref>

== References ==
{{Reflist}}

== External links ==
* {{PPDB|515}}
* [https://npic.orst.edu/factsheets/PermGen.pdf Permethrin General Fact Sheet] National Pesticide Information Center
** [https://npic.orst.edu/factsheets/archive/Permtech.html Permethrin Technical Fact Sheet] National Pesticide Information Center
** [https://npic.orst.edu/pest/mosquito/ptc.html Permethrin-treated Clothing] National Pesticide Information Center
* [https://nap.nationalacademies.org/catalog/9274/health-effects-of-permethrin-impregnated-army-battle-dress-uniforms "Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms"] National Research Council
* [https://extoxnet.orst.edu/pips/permethr.htm Permethrin Pesticide Information Profile] Extension Toxicology Network

{{Human lice}}
{{Anti-arthropod medications}}
{{Insecticides}}
{{Xenobiotic-sensing receptor modulators}}
{{Portal bar | Medicine}}
{{Authority control}}

[[Category:Antiparasitic agents]]
[[Category:Household chemicals]]
[[Category:Organochlorides]]
[[Category:Endocrine disruptors]]
[[Category:(3-phenoxyphenyl)methyl 2,2,3-trimethylcyclopropane-1-carboxylates]]
[[Category:Acaricides]]
[[Category:Over-the-counter drugs in the United States]]
[[Category:World Health Organization essential medicines]]
[[Category:Wikipedia medicine articles ready to translate]]