Editing Pyrethroid

{{Short description|Class of insecticides}}
[[File:Allethrin 2D.svg|300px|thumb|Chemical structure of [[Allethrin]] isomers]]
[[File:Permethrin-2D-skeletal.png|300px|thumb|Chemical structure of [[Permethrin]] isomers]]

A '''pyrethroid''' is an [[organic compound]] similar to the natural [[pyrethrin]]s, which are produced by the flowers of [[pyrethrum]]s (''[[Chrysanthemum cinerariaefolium]]'' and ''[[Chrysanthemum coccineum|C. coccineum]]''). Pyrethroids are used as commercial and household [[insecticides]].<ref name="Ullmann" />

In household concentrations pyrethroids are generally harmless to humans.<ref name=Ullmann>{{Ullmann |doi=10.1002/14356007.a14_263 |chapter=Insect Control |year=2000 |last1=Metcalf |first1=Robert L |isbn=3527306730 }}</ref>  However, pyrethroids are toxic to insects such as [[bee]]s, [[dragonflies]], [[mayflies]], [[Horse-fly|gadflies]], and some other [[invertebrates]], including those that constitute the base of aquatic and terrestrial [[food webs]].<ref name=dc>{{cite news |url=http://archive.dailycal.org/article/108103/study_links_pesticides_to_river_contamination|title=Study Links Pesticides to River Contamination |last=Zaveri |first=Mihir |date=February 4, 2010|work=The Daily Californian|publisher=The [[Daily Californian]]|access-date=9 June 2012}}</ref> Pyrethroids are toxic to [[aquatic organism]]s, especially fish.<ref name=idph>[http://www.idph.state.il.us/envhealth/factsheets/pyrethroid.htm Pyrethroids fact sheet] from the Illinois Department of Public Health.</ref> They have been shown to be an effective control measure for malaria outbreaks, through indoor applications.<ref name=VHEMBE>{{cite Q|Q52880664}}</ref>

==Mode of action==
Pyrethroids are [[excitotoxin|excitotoxic]] to [[axon]]s. They act by preventing the closure of the [[voltage-gated sodium channel]]s in the axonal [[membrane]]s. The sodium channel is a [[membrane protein]] with a [[hydrophilic]] interior. This interior is shaped precisely to allow [[sodium ion#aqueous solutions|sodium ions]] to pass through the membrane, enter the axon, and propagate an [[action potential]]. When the toxin keeps the channels in their open state, the nerves cannot [[repolarization|repolarize]], leaving the axonal membrane permanently [[depolarization|depolarized]], thereby paralyzing the organism.<ref name=Soderlund>{{cite journal |doi=10.1016/s0300-483x(01)00569-8 |pmid=11812616 |title=Mechanisms of pyrethroid neurotoxicity: Implications for cumulative risk assessment |journal=[[Toxicology (journal)|Toxicology]]|volume=171 |issue=1 |pages=3–59 |year=2002 |last1=Soderlund |first1=David M |last2=Clark |first2=John M |last3=Sheets |first3=Larry P |last4=Mullin |first4=Linda S |last5=Piccirillo |first5=Vincent J |last6=Sargent |first6=Dana |last7=Stevens |first7=James T |last8=Weiner |first8=Myra L |bibcode=2002Toxgy.171....3S }}</ref> Pyrethroids can be combined with the synergist [[piperonyl butoxide]], a known [[enzyme inhibitor|inhibitor]] of [[microsomal P450]] enzymes which are important in metabolizing the pyrethroid. By that means, the efficacy (lethality) of the pyrethroid is increased.<ref name=Denholm>{{cite journal |doi=10.1017/S0007485300054262 |title=An unconventional use of piperonyl butoxide for managing the cotton whitefly, ''Bemisia tabaci'' (Hemiptera: Aleyrodidae) |journal=[[Bulletin of Entomological Research]] |volume=88 |issue=6 |pages=601–10 |year=2009 |last1=Devine |first1=G.J |last2=Denholm |first2=I }}</ref> It is likely that there are other mechanisms of intoxication also.<ref name="Soderlund-Bloomquist-1989" /> Disruption of [[neuroendocrine cell|neuroendocrine]] activity is thought to contribute to their irreversible effects on insects, which indicates a pyrethroid action on [[voltage-gated calcium channel]]s (and perhaps other [[voltage-gated ion channel|voltage-gated channels]] more widely).<ref name="Soderlund-Bloomquist-1989" />

==Chemistry and classification==
[[File:(R,R)-(+)-trans-chrysanthemic acid.svg|thumb|(1''R'',3''R'')- or (+)-trans-[[chrysanthemic acid]].]]
Pyrethroids are classified based on their mechanism of biological action, as they do not share a common chemical structure. Many are 2,2-dimethylcyclopropanecarboxylic acid derivatives, like [[chrysanthemic acid]], [[ester]]ified with an [[Alcohol (chemistry)|alcohol]]. However, the [[cyclopropyl]] ring does not occur in all pyrethroids. [[Fenvalerate]], which was developed in 1972, is one such example and was the first commercialized pyrethroid without that group. 

Pyrethroids which lack an α-cyano group are often classified as ''type I pyrethroids'' and those with it are called ''type II pyrethroids''. Pyrethroids that have a common name starting with "cy" have a cyano group and are type II. Fenvalerate also contains an α-[[cyano group]].

Some pyrethroids, like [[etofenprox]], also lack the ester bond found in most other pyrethroids and have an [[ether]] bond in its place. [[Silafluofen]] is also classified as a pyrethroid and has a [[silicon]] atom in the place of the ester. Pyrethroids often have [[chiral centers]] and only certain stereoisomers work efficiently as [[insecticide]]s.<ref>{{Cite journal|last=Ujihara|first=K|date=2019|title=The history of extensive structural modifications of pyrethroids|journal=[[Journal of Pesticide Science]]|volume=44|issue=4|pages=215–224|doi=10.1584/jpestics.D19-102|pmc=6861428|pmid=31777441}}</ref>

==Examples==
{{colbegin}}
*[[Allethrin]], the first pyrethroid synthesized 
*[[Bifenthrin]], active ingredient of ''Talstar'', ''Capture'', ''Ortho Home Defense Max'', and ''Bifenthrine''
*[[Cyfluthrin]], an active ingredient in [[Baygon]], Temprid, Fumakilla Vape Aerosol, Tempo SC, and many more, dichlorovinyl derivative of pyrethrin
*[[Cypermethrin]], including the resolved isomer alpha-cypermethrin, dichlorovinyl derivative of pyrethrin. Commonly found in crawling insect killers and some mosquito sprays.
*[[Cyphenothrin]], active ingredient of K2000 Insect spray sold in Israel. Mostly used in some aerosols as a Cypermethrin substitute in developing countries.
*[[Deltamethrin]], dibromovinyl derivative of pyrethrin
*[[Dimefluthrin]]
*[[Esfenvalerate]]
*[[Etofenprox]]
*[[Fenpropathrin]]
*[[Fenvalerate]]
*[[Flucythrinate]]
*[[Flumethrin]]
*[[Imiprothrin]]
*[[lambda-Cyhalothrin]]
*[[Metofluthrin]]
*[[Permethrin]], dichlorovinyl derivative of [[pyrethrin]] and most widely used pyrethroid.
*[[Phenothrin]] (Sumithrin), active ingredient of [[Anvil (insecticide)|Anvil]]
*[[Prallethrin]]
*[[Resmethrin]], active ingredient of ''Scourge''
*[[Silafluofen]]
*[[tau-Fluvalinate]]
*[[Tefluthrin]]
*[[Tetramethrin]]
*[[Tralomethrin]]
*[[Transfluthrin]], an active ingredient in Baygon and other products.
{{colend}}

==Safety==
===Environmental effects===
Pyrethroids are toxic to insects such as [[bee]]s, [[dragonflies]], [[mayflies]], [[Horse-fly|gadflies]], and some other [[invertebrates]], including those that constitute the base of aquatic and terrestrial [[food webs]].<ref name=dc/> They are toxic to aquatic organisms including fish.<ref name=idph/>

Pyrethroids are usually [[Chemical decomposition|broken apart]] by [[sunlight]] and the atmosphere in one or two days, however when associated with sediment they can persist for some time.{{better reference|date=October 2024}}<ref>{{cite journal |doi=10.1371/journal.pone.0015794 |pmid=21246035 |pmc=3016336 |title=Environmental Modeling and Exposure Assessment of Sediment-Associated Pyrethroids in an Agricultural Watershed |journal=[[PLOS ONE]]|volume=6 |issue=1 |pages=e15794 |year=2011 |last1=Luo |first1=Yuzhou |last2=Zhang |first2=Minghua |bibcode=2011PLoSO...615794L |doi-access=free }}</ref>

Pyrethroids are unaffected by conventional secondary treatment systems at municipal [[wastewater treatment]] facilities. They appear in the effluent, usually at levels lethal to invertebrates.{{better reference|date=October 2024}}<ref name="weston">{{cite journal |doi=10.1021/es9035573 |pmid=20121184 |title=Urban and Agricultural Sources of Pyrethroid Insecticides to the Sacramento-San Joaquin Delta of California |journal= [[Environmental Science & Technology]] |volume=44 |issue=5 |pages=1833–40 |year=2010 |last1=Weston |first1=Donald P |last2=Lydy |first2=Michael J |bibcode=2010EnST...44.1833W }}</ref>

===Humans===
Pyrethroid absorption can happen via skin, inhalation or ingestion.<ref name=":0">{{Cite journal|last1=Bradberry|first1=Sally M.|last2=Cage|first2=Sarah A.|last3=Proudfoot|first3=Alex T.|last4=Vale|first4=J. Allister|date=2005|title=Poisoning due to pyrethroids|journal=[[Toxicological Reviews]]|volume=24|issue=2|pages=93–106|doi=10.2165/00139709-200524020-00003|issn=1176-2551|pmid=16180929|s2cid=32523158}}</ref> Pyrethroids often do not bind efficiently to mammalian [[sodium channel]]s.<ref>{{Cite journal|display-authors=etal|vauthors=Silver KS|date=2014|title=Voltage-gated sodium channels as insecticide targets|journal=[[Advances in Insect Physiology]]|volume=46|pages=389–433|doi=10.1016/B978-0-12-417010-0.00005-7|pmc=6005695|pmid=29928068|isbn=9780124170100}}</ref> They also absorb poorly via skin and human liver is often able to metabolize them relatively efficiently. Pyrethroids are thus much less toxic to humans than to insects.<ref>{{Cite journal|last1=Ray|first1=David E.|last2=Ray|first2=Dr David|last3=Forshaw|first3=Philip J.|date=2000-01-01|title=Pyrethroid Insecticides: Poisoning Syndromes, Synergies, and Therapy|journal=[[Journal of Toxicology: Clinical Toxicology]]|volume=38|issue=2|pages=95–101|doi=10.1081/CLT-100100922|issn=0731-3810|pmid=10778904|s2cid=22213256}}</ref> 

It is not well established if chronic exposure to small amounts of pyrethroids is hazardous or not.<ref>{{Cite journal|last1=Burns|first1=C|last2=Pastoor|first2=T|date=2018|title=Pyrethroid epidemiology: a quality-based review|journal=[[Critical Reviews in Toxicology]]|volume=48|issue=4|pages=297–311|doi=10.1080/10408444.2017.1423463|pmid=29389244|doi-access=free}}</ref> However, large doses can cause acute poisoning, which is rarely life threatening. Typical symptoms include facial [[paresthesia]], itching, burning, dizziness, nausea, vomiting and more severe cases of muscle twitching. Severe poisoning is often caused by ingestion of pyrethroids and can result in a variety of symptoms like seizures, [[coma]], bleeding or [[pulmonary edema]].<ref name=":0" /> There is an association of pyrethroids with poorer early social-emotional and language development.<ref name=VHEMBE />

===Other organisms===
Pyrethroids are very toxic to [[cat]]s, but not to [[dog]]s. Poisoning in cats can result in seizures, fever, [[ataxia]] and even death. Poisoning can occur if pyrethroid containing [[flea treatment]] products, which are intended for dogs, are used on cats. The livers of cats detoxify pyrethroids via [[glucuronidation]] more poorly than dogs, which is the cause of this difference.<ref>{{Cite journal|last1=Boland|first1=L|last2=Angles|first2=J|date=2010|title=Feline permethrin toxicity: retrospective study of 42 cases|journal=[[Journal of Feline Medicine and Surgery]]|volume=12|issue=2|pages=61–71|doi=10.1016/j.jfms.2009.09.018|issn=1532-2750|pmid=19897392|s2cid=206051191|pmc=10911430}}</ref> Aside from cats, pyrethroids are typically not toxic to [[mammal]]s or [[bird]]s.<ref>{{Cite book|title=Veterinary toxicology: basic and clinical principles|vauthors=Gupta RC|publisher=Elsevier|year=2007|isbn=978-0-08-048160-9|edition=1st|pages=676–677|doi=10.1016/B978-012370467-2/50153-X|display-authors=etal}}</ref> They are often toxic to [[fish]], [[reptile]]s and [[amphibian]]s.<ref>{{Cite journal|display-authors=etal|vauthors=Ortiz-Santaliestra ME|date=2018|title=Validity of fish, birds and mammals as surrogates for amphibians and reptiles in pesticide toxicity assessment|journal=[[Ecotoxicology (journal)|Ecotoxicology]]|volume=27|issue=7|pages=819–833|doi=10.1007/s10646-018-1911-y|pmid=29492806|bibcode=2018Ecotx..27..819O |s2cid=3604324}}</ref>

==Resistance==
{{further|Insecticide resistance}}
The use of pyrethroids as insecticides has led to the development of widespread resistance to them among some insect populations, especially mosquitoes.<ref name="Jeran-et-al-2020">{{cite journal | last1=Jeran | first1=Nina | last2=Grdiša | first2=Martina | last3=Varga | first3=Filip | last4=Šatović | first4=Zlatko | last5=Liber | first5=Zlatko | last6=Dabić | first6=Dario | last7=Biošić | first7=Martina | title=Pyrethrin from Dalmatian pyrethrum (''Tanacetum cinerariifolium''/Trevir./Sch. Bip.): biosynthesis, biological activity, methods of extraction and determination | journal=[[Phytochemistry Reviews]] | publisher=[[Springer Science+Business Media]]| volume=20 | issue=5 | date=2020-10-06 | issn=1568-7767 | doi=10.1007/s11101-020-09724-2 | pages=875–905| s2cid=225152789|id=[[Phytochemical Society of Europe]]+[[Phytochemical Society of North America]]. MG [[ORCID]]: [http://orcid.org/0000-0002-4584-4851 0000-0002-4584-4851])}}</ref>

Pyrethroids have been used against bedbugs, but resistant populations have developed to them.<ref name="JAMA2009">{{cite journal |doi=10.1001/jama.2009.405 |pmid=19336711 |title=Bed Bugs ''Cimex lectularius'' and Clinical Consequences of Their Bites |journal=[[JAMA]]|volume=301 |issue=13 |pages=1358–66 |year=2009 |last1=Goddard |first1=Jerome |last2=Deshazo |first2=R |doi-access= }}</ref><ref name="Kolb2009">{{cite journal |doi=10.1111/j.1529-8019.2009.01246.x |pmid=19580578 |title=Bedbugs |journal=[[Dermatologic Therapy]]|volume=22 |issue=4 |pages=347–52 |year=2009 |last1=Kolb |first1=Adam |last2=Needham |first2=Glen R |last3=Neyman |first3=Kimberly M |last4=High |first4=Whitney A |s2cid=221648188 |doi-access=free }}</ref><ref name="voiland">Voiland, Adam.  [http://health.usnews.com/usnews/health/articles/070708/16bedbug.htm "You May not be Alone"] {{webarchive|url=https://web.archive.org/web/20111107010535/http://health.usnews.com/usnews/health/articles/070708/16bedbug.htm |date=2011-11-07 }} U.S. News & World Report 16 July 2007, Vol. 143, Issue 2, p53–54.</ref><ref>{{cite journal |doi=10.1603/0022-2585(2008)45[1092:BAMAOD]2.0.CO;2 |pmid=19058634 |year=2008 |volume=45 |issue=6 |pages=1092–101 |title=Biochemical and Molecular Analysis of Deltamethrin Resistance in the Common Bed Bug (Hemiptera: Cimicidae) |journal=[[Journal of Medical Entomology]]|last1=Yoon |first1=Kyong Sup |last2=Kwon |first2=Deok Ho |last3=Strycharz |first3=Joseph P |last4=Hollingsworth |first4=Craig S |last5=Lee |first5=Si Hyeock |last6=Clark |first6=J. Marshall |doi-broken-date=16 January 2025 |s2cid=27422270 }}</ref> Populations of [[diamondback moth]]s have also commonly developed resistance to pyrethroids<ref>{{cite journal|last1=Leibee|first1=Gary L.|last2=Savage|first2=Kenneth E.|year=1992|title=Evaluation of Selected Insecticides for Control of Diamondback Moth and Cabbage Looper in Cabbage in Central Florida with Observations on Insecticide Resistance in the Diamondback Moth|journal=The Florida Entomologist|volume=75|issue=4|pages=585|doi=10.2307/3496140|issn=0015-4040|jstor=3496140}}</ref>{{better source needed|date=January 2022}} {{endash}} including in U.S. states [[North Dakota]]<ref name="NDSUExt">{{cite web | title=Pyrethroid Complaints for Diamondback Moth Control in Canola (08/26/21) | website=[[NDSU Extension|NDSU Agriculture and Extension]] | date=2021-08-26 | url=http://www.ag.ndsu.edu:8000/agriculture/ag-hub/ag-topics/crop-production/crop-pest-report/entomology/pyrethroid-complaints-diamondback-moth | access-date=2022-01-08 }}{{Dead link|date=December 2024 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> and [[Wisconsin]]<ref name="WiscHortDBM">{{cite web | last=Marsden | first=Christy | title=Diamondback Moth | website=[[Wisconsin Horticulture]] | date=2021-10-15 | url=http://hort.extension.wisc.edu/articles/diamondback-moth/ | access-date=2022-01-08}}</ref> while pyrethroids are still recommended in [[California]].<ref name="UCANRDBM">{{cite web | url=http://www2.ipm.ucanr.edu/agriculture/floriculture-and-ornamental-nurseries/Diamondback-moth/ | title=Diamondback Moth - Floriculture and Ornamental Nurseries Pest Management Guidelines | website=[[University of California Agriculture and Natural Resources]] (UCANR)}}</ref> Various mosquito populations have been discovered to have a high level of resistance, including ''[[Anopheles gambiae sensu lato|Anopheles gambiae s.l.]]'' in [[West Africa]] by Chandre et al 1999 through Pwalia et al 2019, ''[[Anopheles arabiensis|A. arabiensis]]'' in [[Sudan]] by Ismail et al 2018 and [[The Gambia]] by Opondo et al 2019, and ''[[Aedes aegypti]]'' in [[South East Asia]] by Amelia-Yap et al 2018, [[Papua New Guinea]] by Demok et al 2019, and various other locations by Smith et al 2016.<ref name="Jeran-et-al-2020" />

{{Vanchor|[[Knockdown resistance]]|knockdown resistance|kdr}} (''kdr'') is one of the stronger kinds of resistance.<ref name="Molecular" /> ''kdr'' [[mutation]]s confer [[target-site resistance]] to [[DDT]] and pyrethroids and [[cross-resistance]] to DDT.<ref name="Molecular" /> Most ''kdr'' mutations are within or proximate to the two arthropod [[sodium channel]] genes.<ref name="Molecular">{{cite journal|year=2014|publisher=[[Elsevier BV]]|pages=1–17|first8=Boris|first7=Kristopher|volume=50|first6=Lingxin|first5=Peng|first4=Yoshiko|first3=Frank|first2=Yuzhe|first1=Ke|last8=Zhorov|last7=Silver|last6=Wang|last5=Xu|last4=Nomura|last3=Rinkevich|last2=Du|last1=Dong|journal=[[Insect Biochemistry and Molecular Biology]]|issn=0965-1748|id=[[NIHMSID]]: 582398|s2cid=6332754|pmc=4484874|pmid=24704279|doi=10.1016/j.ibmb.2014.03.012|title=Molecular biology of insect sodium channels and pyrethroid resistance|bibcode=2014IBMB...50....1D }}</ref>

==History==
Pyrethroids were introduced by a team of [[Rothamsted Research]] scientists in the 1960s and 1970s following the elucidation of the structures of pyrethrin I and II by [[Hermann Staudinger]] and [[Leopold Ružička]] in the 1920s.<ref name="StaudingerRuzicka1924">{{cite journal |doi=10.1002/hlca.19240070124 |title=Insektentötende Stoffe I. Über Isolierung und Konstitution des wirksamen Teiles des dalmatinischen Insektenpulvers |trans-title=Insecticidal substances I. On isolation and constitution of the active part of the Dalmatian insect powder |journal=[[Helvetica Chimica Acta]]|volume=7 |issue=1 |pages=177–201 |year=1924 |last1=Staudinger |first1=H |last2=Ruzicka |first2=L }}</ref> The pyrethroids represented a major advancement in the chemistry that would synthesize the analog of the natural version found in [[Chrysanthemum#Insecticidal uses|pyrethrum]]. Its insecticidal activity has relatively low [[mammal]]ian [[toxicity]] and an unusually fast biodegradation. Their development coincided with the identification of problems with [[DDT]] use. Their work consisted firstly of identifying the most active components of [[pyrethrum]], extracted from East African chrysanthemum flowers and long known to have insecticidal properties. Pyrethrum rapidly knocks down flying insects but has negligible persistence — which is good for the environment but gives poor efficacy when applied in the field. Pyrethroids are essentially chemically stabilized forms of natural pyrethrum and belong to IRAC MoA group 3 (they interfere with sodium transport in insect nerve cells).<ref name=resistance>{{cite journal |doi=10.1016/j.ibmb.2012.03.008 |pmid=22504519 |title=Identification of mutations associated with pyrethroid resistance in the voltage-gated sodium channel of the tomato leaf miner (Tuta absoluta) |journal=[[Insect Biochemistry and Molecular Biology]]|volume=42 |issue=7 |pages=506–13 |year=2012 |last1=Haddi |first1=Khalid |last2=Berger |first2=Madeleine |last3=Bielza |first3=Pablo |last4=Cifuentes |first4=Dina |last5=Field |first5=Linda M |last6=Gorman |first6=Kevin |last7=Rapisarda |first7=Carmelo |last8=Williamson |first8=Martin S |last9=Bass |first9=Chris |doi-access=free |bibcode=2012IBMB...42..506H |url=https://repository.rothamsted.ac.uk/download/d740e025fe45d0f2cca5d0f582176c8641c90afcf8dc497d6e7ed7fb7407c889/4615152/1-s2.0-S0965174812000471-main.pdf }}</ref>

The ''first-generation pyrethroids'', developed in the 1960s, include [[bioallethrin]], [[tetramethrin]], [[resmethrin]], and bioresmethrin. They are more active than the natural pyrethrum but are unstable in sunlight. With the 91/414/EEC review,<ref>{{cite web|url=http://eur-lex.europa.eu/legal-content/EN/ALL/?uri=CELEX:31991L0414|title=EUR-Lex - 31991L0414 - EN - EUR-Lex|work=europa.eu|date=15 July 1991 }}</ref> many 1st-generation compounds have not been included on Annex 1, probably because the market is not big enough to warrant the costs of re-registration (rather than any special concerns about safety).

By 1974, the Rothamsted team had discovered a ''second generation'' of more persistent compounds notably: [[permethrin]], [[cypermethrin]] and [[deltamethrin]]. They are substantially more resistant to degradation by light and air, thus making them suitable for use in [[agriculture]], but they have significantly higher mammalian toxicities. Over the subsequent decades these derivatives were followed with other proprietary compounds such as [[fenvalerate]], [[lambda-cyhalothrin]] and beta-[[cyfluthrin]]. Most patents have now expired, making these compounds cheap and therefore popular (although permethrin and fenvalerate have not been re-registered under the 91/414/EEC process). 

==References==
{{Reflist|refs=

<ref name="Soderlund-Bloomquist-1989">{{cite journal | last1=Soderlund | first1=David M | last2=Bloomquist | first2=Jeffrey R | title=Neurotoxic Actions of Pyrethroid Insecticides | journal=[[Annual Review of Entomology]] | publisher=[[Annual Reviews (publisher)|Annual Reviews]] | volume=34 | issue=1 | year=1989 | issn=0066-4170 | doi=10.1146/annurev.en.34.010189.000453 | pages=77–96 | s2cid=31881940 | pmid=2539040}}</ref>

}}

{{Insecticides}}

[[Category:Pyrethroids]]
[[Category:Household chemicals]]