A pyrethroid is an organic compound that is a synthetic derivative of pyrethrins produced by the flowers of pyrethrums (Chrysanthemum cinerariaefolium and C. coccineum). Pyrethroids constitute the majority of commercial household insecticides. In the concentrations used in such products, they may also have insect repellent properties.
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).)
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).
Classes of pyrethroidsEdit
The earliest pyrethoids are related to pyrethrin I and II by changing the alcohol group of the ester of chrysanthemic acid. This relatively modest change can lead to substantially altered activities. For example, the 5-benzyl-3-furanyl ester called resmethrin is only weakly toxic to mammals (LD50 (rat, oral) = 2,000 mg/kg) but is 20–50 times more effective than natural pyrethrum and is also readily biodegraded. Other commercially important esters include tetramethrin, allethrin, phenothrin, barthrin, dimethrin, and bioresmethrin. Another family of pyrethroids have altered acid fragment together with altered alcohol components. These require more elaborate organic synthesis. Members of this extensive class include the dichlorovinyl and dibromovinyl derivatives. Still others are tefluthrin, fenpropathrin, and bioethanomethrin.
- 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, 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
- lambda-Cyhalothrin active ingredient in Demand CS (known as Icon CS in Asian region), in a micro capsulated formulation but with a strong paint-like odour.
- 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 beneficial 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, possibly at extremely small levels, such as 4 parts per trillion.
Safety and effectivenessEdit
Earlier studies suggested that most vertebrates have sufficient enzymes for rapid breakdown of pyrethroids, except for cats. Pyrethroids are highly toxic to cats because they do not have glucuronidase, which participates in hepatic detoxifying metabolism pathways.
A recent study, however, suggests that developing mice exposed to deltamethrin (a pyrethroid pesticide) show neurological and behavioral changes resembling Attention-Deficit/Hyperactivity Disorder (ADHD) in humans. In terms of LD50 for rats, Tefluthrin is the most toxic at 29 mg/kg. Anaphylaxis has been reported after pyrethrum exposure, but allergic reaction to pyrethroids has not been documented. Increased sensitivity occurs following repeated exposure to nitrile containing pyrethroids, such as beta-cyfluthrin.
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 this as well. Diamondback moths are also resistant to pyrethroids.
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