A pyrethroid is an organic compound similar to the natural pyrethrins, which are produced by the flowers of pyrethrums (Chrysanthemum cinerariaefolium and C. coccineum). Pyrethroids are used as commercial and household insecticides.
In household concentrations pyrethroids are generally harmless to humans. However, pyrethroids are toxic to insects such as bees, dragonflies, mayflies, gadflies, and some other invertebrates, including those that constitute the base of aquatic and terrestrial food webs. Pyrethroids are toxic to aquatic organisms including fish. It has been shown to be an effective control for malaria through indoor applications.
Mode of actionEdit
Pyrethroids are axonic excitotoxins, the toxic effects of which are mediated through preventing the closure of the voltage-gated sodium channels in the axonal membranes. The sodium channel is a membrane protein with a hydrophilic interior. This interior is shaped precisely to allow 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 repolarize, leaving the axonal membrane permanently depolarized, thereby paralyzing the organism. Pyrethroids can be combined with the synergist piperonyl butoxide, a known inhibitor of key microsomal cytochrome P450 enzymes from metabolizing the pyrethroid, which increases its efficacy (lethality). It is likely that there are other mechanisms of intoxication also. Disruption of neuroendocrine activity is thought to contribute to their irreversible effects on insects, which indicates a pyrethroid action on voltage-gated calcium channels (and perhaps other voltage-gated channels more widely).
Chemistry and classificationEdit
Pyrethroids are mostly defined as pyrethroids based on their biological action, as they do not have common chemical structures. They often contain some 2,2-dimethylcyclopropanecarboxylic acid derivative, like chrysanthemic acid, which is esterified with a large alcohol. Cyclopropyl does not occur in all pyrethroids. Fenvalerate, which was developed in 1972, is one such example and was the first pyrethroid without the cyclopropyl group. Fenvalerate also has an α-cyano group. Pyrethroids which lack this α-cyano group are often classified as type I pyrethroids and those with it are called type II pyrethroids. Some pyrethroids, like etofenprox, lack the ester bond found from most pyrethroids and have an ether bond in its place. Silafluofen is also classified as a pyrethroid and it has silicon atom in the place of an ester. Pyrethroids often have chiral centers and only certain stereoisomers work efficiently as insecticides.
- 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
- Cyphenothrin, active ingredient of K2000 Insect spray sold in Israel and the Palestinian territories
- Deltamethrin, dibromovinyl derivative of pyrethrin
- Permethrin, dichlorovinyl derivative of pyrethrin and most widely used pyrethroid.
- Resmethrin, active ingredient of Scourge
- Sumithrin, active ingredient of Anvil
- Transfluthrin, an active ingredient in Baygon
Pyrethroids are toxic to insects such as bees, dragonflies, mayflies, gadflies, and some other invertebrates, including those that constitute the base of aquatic and terrestrial food webs. They are toxic to aquatic organisms including fish.
Pyrethroid absorption can happen via skin, inhalation or ingestion. Pyrethroids often do not bind efficiently to mammalian sodium channels. 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.
It is not well established if chronic exposure to small amounts of pyrethroids is hazardous or not. 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. There is an association of pyrethroids with poorer early social-emotional and language development.
Pyrethroids are very toxic to cats, but not to dogs. 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. Aside from cats, pyrethroids are typically not toxic to mammals or birds. They are often toxic to fish, reptiles and amphibians.
The use of pyrethroids as insecticides has led to the development of resistance to them among some insect populations. Although bedbugs were almost eradicated in North America through the use of DDT and organophosphates, populations of bedbugs resistant to both have developed. The use of DDT for this purpose was banned, and its reintroduction would not offer a solution to the problem of bedbugs, due to resistance. Pyrethroids became more commonly used against bedbugs, but resistant populations have now developed to them as well. Diamondback moths are also resistant to pyrethroids.
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. The pyrethroids represented a major advancement in the chemistry that would synthesize the analog of the natural version found in pyrethrum. Its insecticidal activity has relatively low mammalian 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).
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, 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).
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