A pyrethroid is an
organic compound
In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. T ...
similar to the natural
pyrethrins, which are produced by the flowers of
pyrethrum
''Pyrethrum'' was a genus of several Old World plants now classified as ''Chrysanthemum'' or ''Tanacetum'' which are cultivated as ornamentals for their showy flower heads. Pyrethrum continues to be used as a common name for plants formerly inclu ...
s (''
Chrysanthemum cinerariaefolium
''Pyrethrum'' was a genus of several Old World plants now classified as ''Chrysanthemum'' or ''Tanacetum'' which are cultivated as ornamentals for their showy flower heads. Pyrethrum continues to be used as a common name for plants formerly inclu ...
'' and ''
C. coccineum''). Pyrethroids are used as commercial and household
insecticides
Insecticides are substances used to kill insects. They include ovicides and larvicides used against insect eggs and larvae, respectively. Insecticides are used in agriculture, medicine, industry and by consumers. Insecticides are claimed t ...
.
In household concentrations pyrethroids are generally harmless to humans.
However, pyrethroids are toxic to insects such as
bees,
dragonflies
A dragonfly is a flying insect belonging to the infraorder Anisoptera below the order Odonata. About 3,000 extant species of true dragonfly are known. Most are tropical, with fewer species in temperate regions. Loss of wetland habitat threa ...
,
mayflies
Mayflies (also known as shadflies or fishflies in Canada and the upper Midwestern United States, as Canadian soldiers in the American Great Lakes region, and as up-winged flies in the United Kingdom) are aquatic insects belonging to the order ...
,
gadflies, and some other
invertebrates
Invertebrates are a paraphyletic group of animals that neither possess nor develop a vertebral column (commonly known as a ''backbone'' or ''spine''), derived from the notochord. This is a grouping including all animals apart from the chordat ...
, including those that constitute the base of aquatic and terrestrial
food webs.
Pyrethroids are toxic to
aquatic organisms, especially fish.
[Pyrethroids fact sheet]
from the Illinois Department of Public Health. They have been shown to be an effective control measure for malaria outbreaks, through indoor applications.
Mode of action
Pyrethroids are
axon
An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action p ...
ic
excitotoxin
In excitotoxicity, nerve cells suffer damage or death when the levels of otherwise necessary and safe neurotransmitters such as glutamate become pathologically high, resulting in excessive stimulation of receptors. For example, when glutamate re ...
s, 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
Membrane proteins are common proteins that are part of, or interact with, biological membranes. Membrane proteins fall into several broad categories depending on their location. Integral membrane proteins are a permanent part of a cell membrane ...
with a
hydrophilic
A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press.
In contrast, hydrophobes are ...
interior. This interior is shaped precisely to allow
sodium ions to pass through the membrane, enter the axon, and propagate an
action potential
An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...
. 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
microsomal cytochrome P450
Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various co ...
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
s which are important in metabolizing the pyrethroid. By that means, the efficacy (lethality) of the pyrethroid is increased.
It is likely that there are other mechanisms of intoxication also.
Disruption of
neuroendocrine
Neuroendocrine cells are cells that receive neuronal input (through neurotransmitters released by nerve cells or neurosecretory cells) and, as a consequence of this input, release messenger molecules (hormones) into the blood. In this way they bri ...
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 classification
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
Chrysanthemic acid is an organic compound that is related to a variety of natural and synthetic insecticides. It is related to the pyrethrin I and II, as well as the pyrethroids. One of the four stereoisomers, (1''R'',3''R'')- or (+)-''trans''- ...
,
ester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides a ...
ified with an
alcohol. However, the
cyclopropyl
A cyclopropyl group is a chemical structure derived from cyclopropane, and can participate in organic reactions that constitute cycloadditions and rearrangement organic reactions of cyclopropane. The group has an empirical formula of C3H5 and che ...
ring does not occur in all pyrethroids.
Fenvalerate
Fenvalerate is a synthetic pyrethroid insecticide. It is a mixture of four optical isomers which have different insecticidal activities. The 2-S ''alpha'' (or SS) configuration, known as esfenvalerate, is the most insecticidally active isomer. F ...
, 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
In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom connected to two alkyl or aryl groups. They have the general formula , where R and R′ represent the alkyl or aryl groups. Ethers can again be ...
bond in its place.
Silafluofen is also classified as a pyrethroid and has a
silicon
Silicon is a chemical element with the symbol Si and atomic number 14. It is a hard, brittle crystalline solid with a blue-grey metallic luster, and is a tetravalent metalloid and semiconductor. It is a member of group 14 in the periodic ta ...
atom in the place of the ester. Pyrethroids often have
chiral centers and only certain stereoisomers work efficiently as
insecticides.
Examples
*
Allethrin
The allethrins are a group of related synthetic compounds used in insecticides. They are classified as pyrethroids, i.e. synthetic versions of pyrethrin, a chemical with insecticidal properties found naturally in ''Chrysanthemum'' flowers. They w ...
, the first pyrethroid synthesized
*
Bifenthrin
Bifenthrin is a pyrethroid insecticide. It is widely used against ant infestations.
It is not a restricted chemical in the United States and is commonly sold in hardware stores to control pests in homes.
Chemical properties
Bifenthrin is poorly ...
, 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
Esfenvalerate is a synthetic pyrethroid insecticide marketed under the brand Asana. It is the (''S'')-enantiomer
In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(en ...
*
Etofenprox
*
Fenpropathrin
*
Fenvalerate
Fenvalerate is a synthetic pyrethroid insecticide. It is a mixture of four optical isomers which have different insecticidal activities. The 2-S ''alpha'' (or SS) configuration, known as esfenvalerate, is the most insecticidally active isomer. F ...
*
Flucythrinate
Flucythrinate is a pyrethroid insecticide and acaricide
Acaricides are pesticides that kill members of the arachnid subclass ''Acari'', which includes ticks and mites.
Acaricides are used both in medicine and agriculture, although the desired s ...
*
Flumethrin
*
Imiprothrin
*
lambda-Cyhalothrin
Cyhalothrin is the ISO common name for an organic compound that, in specific isomeric forms, is used as a pesticide.
It is a pyrethroid, a class of synthetic insecticides that mimic the structure and properties of the naturally occurring insectic ...
*
Metofluthrin
*
Permethrin, dichlorovinyl derivative of
pyrethrin and most widely used pyrethroid.
*
Phenothrin (Sumithrin), active ingredient of
Anvil
*
Prallethrin
*
Resmethrin
Resmethrin is a pyrethroid insecticide with many uses, including control of the adult mosquito
Mosquitoes (or mosquitos) are members of a group of almost 3,600 species of small flies within the family Culicidae (from the Latin ''culex'' meani ...
, active ingredient of ''Scourge''
*
Silafluofen
*
tau-Fluvalinate
*
Tefluthrin
*
Tetramethrin
*
Tralomethrin
*
Transfluthrin, an active ingredient in Baygon and other products.
Environmental effects
Pyrethroids are toxic to insects such as
bees,
dragonflies
A dragonfly is a flying insect belonging to the infraorder Anisoptera below the order Odonata. About 3,000 extant species of true dragonfly are known. Most are tropical, with fewer species in temperate regions. Loss of wetland habitat threa ...
,
mayflies
Mayflies (also known as shadflies or fishflies in Canada and the upper Midwestern United States, as Canadian soldiers in the American Great Lakes region, and as up-winged flies in the United Kingdom) are aquatic insects belonging to the order ...
,
gadflies, and some other
invertebrates
Invertebrates are a paraphyletic group of animals that neither possess nor develop a vertebral column (commonly known as a ''backbone'' or ''spine''), derived from the notochord. This is a grouping including all animals apart from the chordat ...
, including those that constitute the base of aquatic and terrestrial
food webs.
[ They are toxic to aquatic organisms including fish.][
]
Biodegradation
Pyrethroids 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.
Safety
Humans
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
Pulmonary edema, also known as pulmonary congestion, is excessive liquid accumulation in the tissue and air spaces (usually alveoli) of the lungs. It leads to impaired gas exchange and may cause hypoxemia and respiratory failure. It is due t ...
. There is an association of pyrethroids with poorer early social-emotional and language development.
Other organisms
Pyrethroids are very toxic to cat
The cat (''Felis catus'') is a domestic species of small carnivorous mammal. It is the only domesticated species in the family Felidae and is commonly referred to as the domestic cat or house cat to distinguish it from the wild members of ...
s, but not to dog
The dog (''Canis familiaris'' or ''Canis lupus familiaris'') is a domesticated descendant of the wolf. Also called the domestic dog, it is derived from the extinct Pleistocene wolf, and the modern wolf is the dog's nearest living relative. Do ...
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
Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve gl ...
more poorly than dogs, which is the cause of this difference. Aside from cats, pyrethroids are typically not toxic to mammals or bird
Birds are a group of warm-blooded vertebrates constituting the class Aves (), characterised by feathers, toothless beaked jaws, the laying of hard-shelled eggs, a high metabolic rate, a four-chambered heart, and a strong yet lightweig ...
s. They are often toxic to fish
Fish are aquatic, craniate, gill-bearing animals that lack limbs with digits. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish as well as various extinct related groups. Approximately 95% of ...
, reptiles and amphibians.
Resistance
The use of pyrethroids as insecticides has led to the development of widespread resistance to them among some insect populations, especially mosquitoes.[ .]
Although bedbugs were almost eradicated in North America through the use of DDT
Dichlorodiphenyltrichloroethane, commonly known as DDT, is a colorless, tasteless, and almost odorless crystalline chemical compound, an organochloride. Originally developed as an insecticide, it became infamous for its environmental impacts. ...
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.[Voiland, Adam.]
"You May not be Alone"
U.S. News & World Report 16 July 2007, Vol. 143, Issue 2, p53–54. Populations of Diamondback moths have also commonly developed resistance to pyrethroids including in U.S. states North Dakota
North Dakota () is a U.S. state in the Upper Midwest, named after the indigenous Dakota Sioux. North Dakota is bordered by the Canadian provinces of Saskatchewan and Manitoba to the north and by the U.S. states of Minnesota to the east, So ...
and Wisconsin
Wisconsin () is a state in the upper Midwestern United States. Wisconsin is the 25th-largest state by total area and the 20th-most populous. It is bordered by Minnesota to the west, Iowa to the southwest, Illinois to the south, Lake M ...
while pyrethroids are still recommended in California
California is a state in the Western United States, located along the Pacific Coast. With nearly 39.2million residents across a total area of approximately , it is the most populous U.S. state and the 3rd largest by area. It is also the m ...
. Various mosquito populations have been discovered to have a high level of resistance, including '' Anopheles gambiae s.l.'' in West Africa
West Africa or Western Africa is the westernmost region of Africa. The United Nations defines Western Africa as the 16 countries of Benin, Burkina Faso, Cape Verde, The Gambia, Ghana, Guinea, Guinea-Bissau, Ivory Coast, Liberia, Mali, M ...
by Chandre et al 1999 through Pwalia et al 2019, '' A. arabiensis'' in Sudan by Ismail et al 2018 and The Gambia
The Gambia,, ff, Gammbi, ar, غامبيا officially the Republic of The Gambia, is a country in West Africa. It is the smallest country within mainland AfricaHoare, Ben. (2002) ''The Kingfisher A-Z Encyclopedia'', Kingfisher Publicatio ...
by Opondo et al 2019, and ''Aedes aegypti
''Aedes aegypti'', the yellow fever mosquito, is a mosquito that can spread dengue fever, chikungunya, Zika fever, Mayaro and yellow fever viruses, and other disease agents. The mosquito can be recognized by black and white markings on its le ...
'' in South East Asia
Southeast Asia, also spelled South East Asia and South-East Asia, and also known as Southeastern Asia, South-eastern Asia or SEA, is the geographical south-eastern region of Asia, consisting of the regions that are situated south of mainland ...
by Amelia-Yap et al 2018, Papua New Guinea
Papua New Guinea (abbreviated PNG; , ; tpi, Papua Niugini; ho, Papua Niu Gini), officially the Independent State of Papua New Guinea ( tpi, Independen Stet bilong Papua Niugini; ho, Independen Stet bilong Papua Niu Gini), is a country i ...
by Demok et al 2019, and various other locations by Smith et al 2016.
History
Pyrethroids were introduced by a team of Rothamsted Research
Rothamsted Research, previously known as the Rothamsted Experimental Station and then the Institute of Arable Crops Research, is one of the oldest agricultural research institutions in the world, having been founded in 1843. It is located at Harp ...
scientists in the 1960s and 1970s following the elucidation of the structures of pyrethrin I and II by Hermann Staudinger and Leopold Ružička
Leopold Ružička (; born Lavoslav Stjepan Ružička; 13 September 1887 – 26 September 1976) was a Croatian-Swiss scientist and joint winner of the 1939 Nobel Prize in Chemistry "for his work on polymethylenes and higher terpenes" "including t ...
in the 1920s. The pyrethroids represented a major advancement in the chemistry that would synthesize the analog of the natural version found in pyrethrum
''Pyrethrum'' was a genus of several Old World plants now classified as ''Chrysanthemum'' or ''Tanacetum'' which are cultivated as ornamentals for their showy flower heads. Pyrethrum continues to be used as a common name for plants formerly inclu ...
. Its insecticidal activity has relatively low mammalian toxicity
Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subs ...
and an unusually fast biodegradation. Their development coincided with the identification of problems with DDT
Dichlorodiphenyltrichloroethane, commonly known as DDT, is a colorless, tasteless, and almost odorless crystalline chemical compound, an organochloride. Originally developed as an insecticide, it became infamous for its environmental impacts. ...
use. Their work consisted firstly of identifying the most active components of pyrethrum
''Pyrethrum'' was a genus of several Old World plants now classified as ''Chrysanthemum'' or ''Tanacetum'' which are cultivated as ornamentals for their showy flower heads. Pyrethrum continues to be used as a common name for plants formerly inclu ...
, 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
Bioallethrin is a brand name for an ectoparasiticide. It consists of two of the eight stereoisomers of allethrin I in an approximate ratio of 1:1. The name ''Bioallethrin'' is a registered trademark of Sumitomo Chemical.
''Esbiothrin'' (CAS numb ...
, tetramethrin, resmethrin
Resmethrin is a pyrethroid insecticide with many uses, including control of the adult mosquito
Mosquitoes (or mosquitos) are members of a group of almost 3,600 species of small flies within the family Culicidae (from the Latin ''culex'' meani ...
, 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
Agriculture or farming is the practice of cultivating plants and livestock. Agriculture was the key development in the rise of sedentary human civilization, whereby farming of domesticated species created food surpluses that enabled people t ...
, but they have significantly higher mammalian toxicities. Over the subsequent decades these derivatives were followed with other proprietary compounds such as fenvalerate
Fenvalerate is a synthetic pyrethroid insecticide. It is a mixture of four optical isomers which have different insecticidal activities. The 2-S ''alpha'' (or SS) configuration, known as esfenvalerate, is the most insecticidally active isomer. F ...
, lambda-cyhalothrin
Cyhalothrin is the ISO common name for an organic compound that, in specific isomeric forms, is used as a pesticide.
It is a pyrethroid, a class of synthetic insecticides that mimic the structure and properties of the naturally occurring insectic ...
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
{{Insecticides
Pyrethroids
Household chemicals