Pyrethroid

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. 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. 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). 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. 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. They are usually broken apart by sunlight and the atmosphere in one or two days, however when associated with sediment they can persist for some time. Pyrethroids are unaffected by conventional secondary treatment systems at municipal wastewater treatment facilities. They appear in the effluent, usually at levels lethal to invertebrates.