Pyrethroids

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Pyrethroids are synthetic insecticides that are based on the main active ingredients of the natural insecticide pyrethrum . A definition based on the chemical structure alone is not possible. The structure of a pyrethroid should be derived from one of the natural pyrethrins and its biological properties should essentially correspond to those of the known pyrethroids. Typical of pyrethroids are their rapid effectiveness (“ knock down ”) even at low doses, their low toxicity for warm-blooded animals , lipophilicity and a low vapor pressure . Pyrethroids are cheaper and can be produced in larger quantities than pyrethrum, and they are usually more effective. Some pyrethroids are photostable and therefore relatively long-lived.

history

Pyrethrin I, model for the pyrethroids

The effective components of the pyrethrum were determined around 1924 by Leopold Ružička and Hermann Staudinger . They largely clarified the structure of the effective pyrethrins and produced the first synthetic derivatives. The commercially produced pyrethroids can be assigned to four different generations depending on the development time.

Structure of allethrin I (R = −CH 3 ), the first pyrethroid, and allethrin II (R = −COOCH 3 )

Only allethrin I , which was first synthesized in 1949 and brought onto the market in 1954 by the Japanese company Sumitomo Chemical , whose structure is still very similar to pyrethrin I, belongs to the first generation . It decomposes very quickly when exposed to light, and synthesis is complex. Allethrin I is less effective against most insects than natural pyrethrins. A second generation of pyrethroids came from 1965 to 1973 with tetramethrin , resmethrin , bioresmethrin , bioallethrin and phenothrin to market. Some active ingredients of this second generation were 20 times (resmethrin) or 50 times (bioresmethrin) more effective than pyrethrum. Fenvalerate and permethrin are active ingredients of the third generation of pyrethroids. Due to their improved photostability, they were the first pyrethroid active ingredients to be used in agriculture.

Flucythrinate

All active ingredients that came onto the market later belong to the fourth generation, which includes, for example, bifenthrin , cypermethrin , cyfluthrin , deltamethrin , flucythrinate and prallethrin . The economic breakthrough of the pyrethroids came with the introduction of photostable compounds for agriculture. In 1976 pyrethroids with a retail value of US $ 10 million were sold on the world market; in 1983 it was US $ 630 million. This commercial success was based almost entirely on fenvalerate , deltamethrin , cypermethrin, and permethrin . The number of pyrethroids synthesized so far on a laboratory scale is estimated at around 1,000.

Michael Elliott of the British Rothamsted Research , whose group developed bioresmethrin and resmethrin in the 1960s and later deltamethrin, cypermethrin and permethrin in the 1970s, played a major role in the development .

Chemical structures

Allethrin I, an ester consisting of chrysanthemum acid (red) and the alcohol residue allethrolone (blue)

The naturally occurring pyrethrins and the majority of pyrethroids are esters of an acid component and an alcohol residue. The molecules usually have one or more centers of chirality , which means that the enantiomers or diastereomers that can be distinguished are almost always differently effective. Allethrin is, for example, the ester of the racemic alcohol allethrolone with racemic cis / trans - chrysanthemum acid . For the production of the far more effective bioallethrin , only (1 R ) - trans -Chrysanthemum acid is used with an identical structure . The same applies to ( S ) -Bioallethrin, which also only consists of the ( S ) -enantiomer of allethrolone.

Components of some early pyrethroids, all with chrysanthemum acid residue (red)

In the search for new active ingredients, the chrysanthemum acid residue was initially retained and the alcohol component varied. For example, it has been replaced by a 3,4-dimethylbenzyl radical (dimethrin), furyl (resmethrin) or phthalimide derivatives (tetramethrin). At the beginning of the 1970s, the alcohol residue was replaced by a 3-phenoxybenzyl group, in which the effectiveness can be increased significantly by adding a cyano group at the α position ( cyphenothrin and others).

By inserting a dichloro, dibromo or difluorovinyl group into the chrysanthemum acid residue , photostable pyrethroids such as permethrin, deltamethrin and cypermethrin could be produced. The replacement of chrysanthemum acid by derivatives of phenylacetic acid also led to photostable products, as with fenvalerate.

Physico-chemical properties

The pyrethroids are highly lipophilic, their logarithmic octanol-water partition coefficient is in the range from 4.2 (tetramethrin) to 8.6 (flumethrin). The water solubility is low to very low with 5 mg / l (tetramethrin) to 0.0003 mg / l (flumethrin).

Mode of action

Like pyrethrum, pyrethroids are contact poisons that irreversibly block the voltage-dependent sodium channels in the nerve membranes so that they cannot be closed again from the open state. As a rule, they act very quickly against almost all insects. The effect occurs more quickly with the less lipophilic pyrethroids than with the highly lipophilic. Pyrethroids are not beneficial to beneficial organisms. However, they also have a disgraceful effect , which means that, for example, their high toxicity to bees in the wild does not come into play. They are also very toxic to fish, amphibians and reptiles.

By blocking the sodium channels, there is a spastic paralysis ( paralysis ) of insects and a fast immobilizing effect, which occurs before the death and " knock down is called".

Resistances

Resistance to pyrethroids is mainly due to the increased production of degrading enzymes such as esterases and “mixed-functional” oxidases . At a high activity of these enzymes also some other insecticides such are DDT , organophosphate and carbamates degrade faster, this is called cross-resistance . Synergists such as the frequently used piperonyl butoxide disrupt the enzymatic breakdown of pyrethroids. This improves their effectiveness and makes it more difficult to develop resistance. When developing new active ingredients, attempts are made to reduce the enzymatic degradability by adapting the molecular structure. Some insecticides from other families of active ingredients are first converted into their "active" form by esterases and oxidases. They show a "negative cross-resistance", that is, they have a stronger effect on pyrethroid-resistant insect strains than on non-resistant ones.

Resistance to pyrethroids can also be acquired if the protein in the nerve cell's sodium channel is changed. Several changes in the α-subunit of the channel protein (VGSC protein) caused by mutations are known, which occur individually or together and lead to an insensitivity to the pyrethroid. Since the inhibition of the sodium channel triggers a rapid immobilization of the insects through spastic paralysis, which is referred to as " knockdown ", the resistances are called " knockdown resistance " (abbreviated kdr ). While individual mutations reduce the sensitivity to all pyrethroids by a factor of 20 to 50, other mutations, also known as " super-kdr ", can increase the tolerance for certain type I pyrethroids by a factor of 500. These mutations, on the other hand, increase susceptibility to two other classes of insecticides, the N -alkylamides and the dihydropyrazoles. However, the most common form of resistance is now a combination of three point mutations (M815I, T917I, L920F), which are becoming increasingly common. In 2010–2012, these mutations were found in 33–100% of head lice in California, Florida and Texas, 97% in Canada and 98.7% in Paris.

use

medicine

Pyrethroids are insecticidal active ingredients in preparations against lice . In Germany, allethrin and permethrin are active ingredients of approved preparations against head lice , felt lice and clothing lice as well as against itch mites ( scabies ). Since 2004, an ointment containing permethrin has also been approved there for the treatment of scabies. In a study in Wales, head lice found resistance or decreased effectiveness of pyrethroids in 82% of cases . An Israeli study also reported widespread pyrethroid resistance in head lice. According to the Robert Koch Institute , these results cannot be directly transferred to Germany, where so far only a few resistant lice have appeared.

Vector control

Some states require that insecticides be applied to the interior of arriving aircraft to prevent disease vectors from being introduced. For this purpose, pyrethroids with short-term effects (pyrethrins, d-phenothrin, resmethrin, bioresmethrin) are sprayed into the cabin air, substances with long-term effects (permethrin) are used to treat surfaces.

Pyrethroids now play an important role in combating the malaria-transmitting Anopheles mosquitoes . However, you can not (for spraying the walls in the same way as DDT English Indoor Residual Spraying ) are used. Their strong repellent effect prevents the mosquitoes from settling on the walls. If mosquitoes do settle down, they are numbed by the " knock down " effect, fall to the floor and often recover after a while. Long-lasting pyrethroids are used to impregnate mosquito nets, which has been recommended by the WHO since 1992 for combating malaria.

Veterinary medicine

In veterinary medicine, pyrethroids are used to repel or treat ectoparasites in pets . These include head and willow flies, horseflies , fleas and animal lice , louse flies , ticks , various mites , hair and feather flies . In Germany, cyfluthrin , cypermethrin , deltamethrin , flumethrin and permethrin are currently approved drugs for this purpose, in the past fenvalerate and flucythrinate were also approved. For food-producing animals, according to Annex 1 of Regulation (EEC) No. 2377/90 on maximum levels for veterinary drug residues in food, cypermethrin, cyhalothrin , cyfluthrin, deltamethrin, flumethrin, fenvalerate and permethrin are permitted in the EU .

Cypermethrin and Deltamethrin have a particularly long-lasting effect and are therefore used preventively as active ingredients in insect-repellent ear tags or collars. To protect against the Varroa mite in honey bees, strips soaked in fluvalinate or flumethrin are hung in the hives. In fish farming, cypermethrin can be used against salmon and fish lice .

There are restrictions on the use of pyrethroids in cats because they are more difficult to break down than many other animal species. Cats are therefore particularly susceptible to pyrethroid poisoning, which is usually fatal for them.

Plant protection

One of the main areas of application for pyrethroids is against caterpillars in cotton cultivation. Pyrethroids continue to be used against a wide variety of insect pests; Exceptions are the woolly and scale insects , which protect themselves well, as well as the hardly sensitive phytopathogenic mite species.

In Germany, the total amount of pyrethroids used as pesticides is low. In 2001, with 52  tons, only about 0.8% of the insecticides used in crop protection were pyrethroids. Because of their high effectiveness, only application rates of 10 to 200 g of active ingredient per hectare are required, which is significantly less than with most other insecticides.

In Germany and Austria, alpha- and zeta-cypermethrin, esfenvalerate , deltamethrin and lambda-cyhalothrin are approved for a relatively wide range of uses, particularly in the cultivation of grain and rape . The use of cypermethrin is permitted in Austria and Switzerland. In Switzerland, as well as alpha- and zeta-cypermethrin and deltamethrin and bifenthrin and cypermethrin high-cis permissible pesticide active ingredients . The areas of application can be different: Cyfluthrin is approved in Germany against codling moth, in Switzerland against storage pests and in Austria for a variety of agricultural applications. Tefluthrin and beta-cyfluthrin are components of seed treatments approved in Germany and Austria .

Pest Control and Households

In 2000, the member companies of the Agricultural Industry Association, which cover around 70% of the market, sold 2.7 t of pyrethroids for “domestic use” in Germany. For this purpose each year about 2.6 t permethrin for the equipment used by wool carpets from moth and beetle.

Pyrethroids, which have been used in households, are very long-lived and represent a persistent contamination. Permethrin is only degraded by 10% within 112 days, and similar courses have been observed for cypermethrin.

toxicology

Pyrethroids are only partially absorbed through the digestive system; their absorption through the skin is very low and therefore occurs mainly through breathing. Resorbed pyrethroids are largely broken down in the body within a few hours or days by esterases and monooxygenases . An accumulation in the fatty tissue is possible, there the half-life for the degradation is up to 30 days.

The acute toxicity of pyrethroids in warm-blooded animals is low compared to insecticides from the groups of organophosphates and organochlorine compounds . The LD 50 in rats for pyrethroids is between 100 and 5000 mg / kg body weight. Acute poisoning in humans occurs rarely. After oral ingestion, nausea, vomiting or diarrhea occur within 10 to 60 minutes. If a significant amount has been absorbed, the patient will suffer from impaired consciousness and convulsions for a few days. Permanent nerve damage after acute poisoning is possible. Direct skin contact with the pure substances or surfaces heavily contaminated with them can lead to local paresthesias within a few minutes to a few hours . The sensitive nerve endings in the skin are irritated, causing tingling, burning or itching that lasts for about a day. Children are generally more sensitive to skin contact with pyrethroids because of their more sensitive skin.

Permethrin (type I pyrethroid)

Type I pyrethroids (without alpha-cyano group) and type II pyrethroids (with alpha-cyano group) differ in terms of their acute effects. In animal experiments, type I leads to the “T syndrome”, named after the tremor that occurs . Ataxia , increased excitability and hypersensitivity to stimuli are also observed in the "T syndrome" .

Cypermethrin (type II pyrethroid)

Type II pyrethroids cause a "CS syndrome", which is named after the characteristic symptoms of choreo - athetosis (involuntary slow movements) and salivation . A gross tremor and clonic convulsions also occur here.

In animal experiments, pyrethroids showed no embryotoxic or teratogenic effects. The US EPA has classified permethrin as a likely carcinogen if ingested orally . This was done on the basis of reproducible studies with mice that developed lung and liver tumors after feeding with permethrin.

Various pyrethroids act as endocrine disruptors , especially androgen receptors. In rabbits, cypermethrin has been found to bind to the testosterone receptor and thus damage male sexual development and the immune system. Permethrin can also bind to the testosterone receptor, but in high concentrations it can act like estrogen . Fenvalerate inhibits the function of thyroid hormones in mice.

Environmental behavior

Pyrethroids do not accumulate via the food chain . Residues in food are a result of direct contamination.

proof

Since pyrethroids are among the most toxic insecticides for aquatic organisms, an analytical detection method is necessary for surface waters, which is very sensitive, i.e. H. extends to the range of picograms per liter.

Other detection methods are based, for example, on determining the concentrations of metabolites in urine or house dust samples.

Web links

Individual evidence

  1. a b c d J. H. Davies: The pyrethroids: an historical introduction . In: JP Leahey (Ed.): The Pyrethroid Insecticides . Taylor & Francis, London / Philadelphia 1985, ISBN 0-85066-283-4 .
  2. a b Bhupinder PS Khambay: Pyrethroid Insecticides . (PDF; 144 kB) Pesticide Outlook - April 2002, pp. 49–54.
  3. George W. Ware, David M. Whitacre: An Introduction to Insecticides . Excerpt from: The Pesticide Book , 6th Edition, 2004 (accessed September 22, 2007).
  4. a b c J. J. Hervé: Agricultural, public health and animal health usage . in JP Leahey (Ed.): The Pyrethroid Insecticides . Taylor & Francis, London / Philadelphia 1985, ISBN 0-85066-283-4 .
  5. a b c d Susanne Smolka, Patricia Cameron: Dangers from hormonally effective pesticides and biocides ( Memento from November 9, 2012 in the Internet Archive ) (PDF; 1.1 MB) . WWF Germany (Ed.), Frankfurt am Main, as of May 2002.
  6. ^ Klaus Naumann: Synthetic Pyrethroid Insecticides: Structures and Properties . Springer-Verlag, Berlin, 1990, ISBN 0-387-51313-2 .
  7. a b Entry on permethrin at Vetpharm, accessed on August 5, 2012.
  8. Olivier Chosidow, Bruno Giraudeau: Topical Ivermectin - A Step toward Making Head Lice Dead Lice? In: New England Journal of Medicine. 2012, Volume 367, Edition 18 of November 1, 2012, pp. 1750–1752, doi: 10.1056 / NEJMe1211124 .
  9. ^ Richter, Müller-Stöver, Walter, Mehlhorn, Häussinger: Head lice - dealing with a resurgent parasitosis . In: Deutsches Ärzteblatt. 102, September 9, 2005, pp. A-2395.
  10. Haustein, Paasch: Scabies still common: Endemics in nursing homes require consistent synchronous treatment . In: Deutsches Ärzteblatt. 102, January 10, 2005, p. A-45.
  11. aerzteblatt-studieren.de: Welsh head lice try out resistance - frequent pyrethoride resistances. ( Memento of September 4, 2007 in the Internet Archive ) June 16, 2006.
  12. BfR : New method for aircraft disinfection protects passengers and crew (PDF; 40 kB).
  13. Christian Felten: Air quality in the cabin (with special consideration of pyrethroids) , May 15, 2003. ( Memento of December 3, 2008 in the Internet Archive )
  14. Christian Simon : DDT - cultural history of a chemical compound . Christoph Merian Verlag, Basel 1999, ISBN 3-85616-114-7 .
  15. Medicines Commission: Use restrictions for pyrethroids in cats. (No longer available online.) ABDA , archived from the original on January 23, 2007 ; Retrieved November 13, 2012 .
  16. ^ Opinion of the "Human Biomonitoring" commission of the Federal Environment Agency: Internal exposure of the general population in Germany to pyrethroids and reference values ​​for pyrethroid metabolites in urine. In: Federal Health Gazette . 48 (2005), pp. 101187-101193.
  17. Federal Office for Agriculture (Switzerland): List of Plant Protection Products .
  18. BVL (Germany): List of approved plant protection products .
  19. Plant protection product register. Retrieved June 28, 2019 .
  20. Lia Emi Nakagawa, Cristiane Mazarin do Nascimento, Alan Roberto Costa, Ricardo Polatto, Solange Papini: Persistence of indoor permethrin and estimation of dermal and non-dietary exposure . In: Journal of Exposure Science & Environmental Epidemiology . March 2019, doi : 10.1038 / s41370-019-0132-7 .
  21. ^ Allum pediatrician portal .
  22. ^ A b Franz-Xaver Reichl (Ed.): Pocket Atlas of Toxicology . Georg Thieme Verlag, Stuttgart 1997, ISBN 3-13-108971-7 .
  23. a b c Forth, Henschler, Rummel, Förstermann, Starke: General and special pharmacology and toxicology . 8th edition. Urban & Fischer, Munich 2001, ISBN 3-437-42520-X .
  24. H Mueller Mohnssen: Chronic sequelae and irreversible injuries Following acute pyrethroid intoxication , Toxicology Letters, Volume 107, Issue 1-3, June 30, 1999, pp 161-176 doi: 10.1016 / S0378-4274 (99) 00043-0 .
  25. EPA (2009): Permethrin Facts. , United States Environmental Protection Agency, Washington DC 2009, accessed June 30, 2017 (PDF).
  26. Christoph Moschet, Etiënne LM Vermeirssen, Remo Seiz, Hildegard Pfefferli, Juliane Hollender: Picogram per liter detections of pyrethroids and organophosphates in surface waters using passive sampling . In: Water Research . tape 66 , December 2014, p. 411-422 , doi : 10.1016 / j.watres.2014.08.032 .
  27. Andrea Rösch, Birgit Beck, Juliane Hollender, Christian Stamm, Heinz Singer: Low concentrations with great effect - detection of pyrethroid and organophosphate insecticides in Swiss streams in the pg · l - range . In: Aqua & Gas . tape 11 , 2019, pp. 54-66 ( PDF ).
  28. Edith Berger-Preiß, Susanne Gerling, G. Leng, et al: Pyrethrum and pyrethroid metabolites (after liquid phase extraction) in urine [Biomonitoring Methods, 2013] . In: The MAK Collection for Occupational Health and Safety. Pt.4: Biomonitoring methods. Vol.13 . 2013, ISBN 978-3-527-60041-0 , pp. 215–248 , doi : 10.1002 / 3527600418.bi800334e0013b ( fraunhofer.de ).