 λ-cyhalothrin (racemic) | |
| Names | |
|---|---|
| IUPAC name (R)-α-cyano-3-phenoxybenzyl (1S)-cis-3-[(Z)-2-chloro-3,3,3-trifluoropropenyl]-2,2-dimethylcyclopropanecarboxylate and (S)-α-cyano-3-phenoxybenzyl (1R)-cis-3-[(Z)-2-chloro-3,3,3-trifluoropropenyl]-2,2-dimethylcyclopropanecarboxylate | |
| Other names Cyhalothrine | |
| Identifiers | |
| |
| |
3D model (JSmol) |
|
| ChEBI |
|
| ChEMBL |
|
| ChemSpider | |
| ECHA InfoCard | 100.062.209 |
| EC Number |
|
| RTECS number |
|
| UNII |
|
| UN number | 2588 |
| |
| |
| |
| Properties[1] | |
| C23H19ClF3NO3 | |
| Molar mass | 449.85 g·mol−1 |
| Appearance | Colourless solid |
| Density | 1.33 g/cm3 |
| Melting point | 49.2 °C (120.6 °F; 322.3 K) |
| Boiling point | Decomposes before boiling |
| 0.005 mg/L [20 °C] | |
| Solubility in other solvents | Very soluble in hexane, toluene, methanol, acetone |
| logP | 5.5 |
| Acidity (pKa) | Not applicable |
| Pharmacology | |
| QP53AC06 (WHO) | |
| Hazards[2] | |
| GHS labelling: | |
   | |
| Danger | |
| H301,H312,H330,H410 | |
| P260,P264,P270,P271,P273,P280,P284,P301+P310,P302+P352,P304+P340,P310,P312,P320,P321,P322,P330,P363,P391,P403+P233,P405,P501 | |
| NFPA 704 (fire diamond) | |
| Flash point | 225 °C (437 °F; 498 K) |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Cyhalothrin (ISOcommon name[3]) is anorganic compound that, in specific isomeric forms, is used as apesticide.[4]It is apyrethroid, a class of syntheticinsecticides that mimic the structure and properties of the naturally occurring insecticidepyrethrin which is present in the flowers ofChrysanthemum cinerariifolium. Pyrethroids, such as cyhalothrin, are often preferred as an active ingredient in agricultural insecticides because they are more cost-effective and longer acting than natural pyrethrins. λ-and γ-cyhalothrin are now used to control insects andspider mites in crops including cotton, cereals, potatoes and vegetables.[5]
Gamma-cyhalothrin[6] andlambda-cyhalothrin[1] are theactive ingredients in the current commercial products based on cyhalothrin. Both arecyanohydrinesters of cis-3-[(Z)-2-chloro-3,3,3-trifluoropropenyl]-2,2-dimethylcyclopropanecarboxylic acid. All of the insecticidal activity is due to the proportion ofabsolute stereochemistry (1R) in the mixture.[7] The active isomer ofdeltamethrin, (1R)-cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylic acid, has the same stereochemistry.
γ-cyhalothrin (a singlechiral isomer) is indeed twice as active as λ-cyhalothrin on a weight-for-weight basis. The latter isracemic and contains the (1R) and inactive (1S) isomers in equal amounts.
By 1974, a team ofRothamsted Research scientists had discovered three pyrethroids (MoA 3a),[8] suitable for use inagriculture, namelypermethrin,cypermethrin and deltamethrin.[9] These compounds were subsequentlylicensed by theNRDC, as NRDC 143, 149 and 161 respectively, to companies which could then develop them for sale in defined territories.Imperial Chemical Industries (ICI) obtained licenses to permethrin and cypermethrin but their agreement with the NRDC did not allow worldwide sales. Also, it was clear to ICI's own researchers atJealott's Hill that future competition in the marketplace might be difficult owing to the greaterpotency of deltamethrin compared to the other compounds. For that reason, in the period 1974–1977, chemists there soughtpatentable analogues which might have advantages compared to the Rothamsted insecticides by having widerspectrum or greatercost-benefit. The first breakthrough was made when atrifluoromethyl group was used to replace one of the chlorines in cypermethrin, especially when the double bond was in itsZ form. The resulting material was found to be more potent than cypermethrin, to which it is most closely related, but also with good activity against thespider miteTetranychus urticae, which added to its attractiveness as a potential new product.[10] The second breakthrough occurred when ICI process chemists developed a practical manufacturing process for the Z-cis acid, by controlling thestereochemistry of the cyclopropane ring in addition to that of the double bond.[11] This led to the initial commercialisation of cyhalothrin, under the trade name Grenade, but the resulting material was still a mixture of four isomers owing to theracemic nature of the Z-cis acid and because the alpha-cyano group was a 1:1 mixture of possibleR and S configurations.[12]
The process work made available a relatively large supply of the Z-cis acid and hence allowed two further commercially important steps to be taken. The first was to make the development and sales oftefluthrin feasible and the second was to spur research directed at making compositions of cyhalothrin with fewer isomers in the sales product. After further research and field tests, ICI chose to focus on λ-cyhalothrin, the mixture containing the single most active isomer together with its mirror image. This so-called "enantiomer pair", ICI code number PP321, could be used after a process for its economic production and purification was developed using crystallisation with recycling of the unwanted enantiomer pair.[13][14]
The new product was first launched in nine countries in 1985 using the trademark Karate.[15] At that time, γ-cyhalothrin, ICI code number PP345, was not a feasible alternative product owing to the difficulty of manufacturing that isomer alone, especially if this involved recycling the "wrong" isomer of the Z-cis acid.In 2000, the agrochemical business of ICI merged with that ofNovartis to formSyngenta, which still manufactures and supplies λ-cyhalothrin. The patents covering the parent compound expired in most major markets in 2003.[16]FMC has entered the market as a supplier of γ-cyhalothrin for use as a broad-spectrum insecticide under the brand name Scion.[17]
Pyrethroids, including cyhalothrin, disrupt the functioning of the nervous system in an organism. They are fast-actingaxonicexcitotoxins, the toxic effects of which are mediated by preventing the closure of thevoltage-gatedsodium channels inaxonal membranes. The sodium channel is amembrane protein with ahydrophilic interior. This interior is shaped precisely to allowsodium ions to pass through the membrane, enter the axon, and propagate anaction potential. The binding of the insecticide to the protein keeps the channels in their open state, so the nerves cannotrepolarize, thereby paralyzing the organism.[18]One consequence of the mode of action is that cyhalothrin has useful knockdown properties. That is, affected larvae rapidly cease feeding and may fall off the crop; flying insects drop to the ground. Paralysis and death follows provided the insect has absorbed a sufficient dose.
λ-cyhalothrin is made available to end-users only informulated products. Since the active ingredient has very low solubility in water, formulations aid its use in water-based sprays by creating anemulsion when diluted. Modern products use non-powdery formulations with reduced or no use of hazardous solvents: Examples include the capsule suspensions Warrior II[19] and Tandem, a mix withthiamethoxam,[20] both sold by Syngenta in the USA.
All pesticides are required to seekregistration from appropriate authorities in the country in which they will be used.[21] In theUnited States, theEnvironmental Protection Agency (EPA) is responsible for regulating pesticides under theFederal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and theFood Quality Protection Act (FQPA).[22] A pesticide can only be used legally according to the directions on the label that is included at the time of the sale of the pesticide. The purpose of the label is "to provide clear directions for effective product performance while minimizing risks to human health and the environment". A label is a legally binding document that mandates how the pesticide can and must be used and failure to follow the label as written when using the pesticide is a federal offence.[23]Within the European Union, a 2-tiered approach is used for theapproval and authorisation of pesticides. Before a formulated product can be developed for market, the active substance must be approved for the European Union. After this has been achieved, authorisation for the specific product must be sought from every Member State that the applicant wants to sell it to. Afterwards, there is a monitoring programme to make sure the pesticide residues in food are below the limits set by theEuropean Food Safety Authority.
The first, and still main, use of λ-cyhalothrin is to control the larvae oflepidopteran pests on crops such as cotton and cereals.
Once an active ingredient has achieved registration in major territories, suppliers often expand the market by seeking label approval[23] for additional crops and pests, afterfield trials have been carried out to confirm the efficacy of the product in the new situation. In the case of λ-cyhalothrin, the current US label includes its use on alfalfa; canola; corn; rice; sorghum; cereals including barley, oats and wheat; vegetable crops including broccoli, cabbage and cauliflower; cotton; legumes including soybeans; lettuce; onion; peanuts; fruit including apples and pears; sugarcane; sunflower, and tobacco.[19] The estimated annual use of λ-cyhalothrin in US agriculture is mapped by the US Geological Survey.[24] While the original use was almost exclusively in cotton, the compound is now applied to many crops. In 2018, the latest date for which figures are available, 600,000 pounds (270,000 kg) were used. The equivalent map for γ-cyhalothrin is also available but its use was never high and is now declining.[25]
Many insecticides, includingDDT have been used to controlmosquito species carrying the malaria parasite. The use of insecticide-treated bed nets has been shown to be an effective preventative measure.[26] TheWorld Health Organization (WHO) has approved λ-cyhalothrin (as its 2.5% capsule suspension formulation) for this use.[27]
In 2003, the EPA approved the use of Impasse termite blocker containing λ-cyhalothrin to controltermites around building foundations, especially where plumbing, electrical, and other utilities penetrated the concrete. Use in this way was intended to give long-term protection from the pest.[28] FMC later introduced a similar product using γ-cyhalothrin[17]
Cyhalothrin is arestricted use pesticide. One consequence of this is that (in the USA) it is a violation of federal law to use the product in a manner inconsistent with its labelling and the labelling must be in possession of the user at the time of the application.[19] It can be absorbed into the body by inhalation of dust or mist and by ingestion. It causes serious eye irritation. Symptoms of poisoning include burning sensation, convulsions, cough, laboured breathing, shortness of breath, sore throat.[2] Skin exposure may also result in a sensation described as a tingling, itching, burning, or prickly feeling. Onset may occur immediately to four hours after exposure and may last 2–30 hours, without damage.First aid measures are included with the label information.[19]
TheWorld Health Organization (WHO) andFood and Agriculture Organization (FAO) joint meeting on pesticide residues has determined that theacceptable daily intake for λ-cyhalothrin is 0–0.02 mg/kg bodyweight per day.[29][30]TheCodex Alimentarius database maintained by the FAO lists the maximum residue limits for cyhalothrin isomers in various food products.[31]
While cyhalothrin is inherently highly toxic to many fish and aquatic invertebrate species, binding to soil and sediment reduces exposure and lessens the risk to fish: field studies found no significant adverse effects: according to theWHO expert committee, "The concentrations of cyhalothrin and lambda-cyhalothrin that are likely to arise in water from normal agricultural application will be low. Since the compound is rapidly adsorbed and degraded under natural conditions, there will not be any practical problems concerning the accumulation of residues or the toxicity of cyhalothrin or lambda-cyhalothrin in aquatic species.[13]
Honeybees,Apis mellifera have been shown to be particularly sensitive to λ-cyhalothrin, with fatal doses as small as 0.04 micrograms per bee.[1] However, field studies found few effects.[citation needed] Nevertheless, due to this sensitivity andpollinator decline, all pyrethroids are recommended to be applied at night to avoid typical pollinating hours, and not to be used in dust form.[32]
In laboratory studies, alkaline water (pH of 9) degraded λ-cyhalothrin with an approximate half-life of 7 days, although at neutral and acidic pHs, degradation did not occur. Sunlight accelerates degradation in water and soil. Its half-life on plant surfaces is 5 days and it has a low potential to contaminate ground water due to its low water solubility and high potential to bind to soil organic matter.[1][33]TheLD50 is 56 mg/kg (rats, oral)[1] and its effects on the environment have been summarized in many publications.[13][34][35][36]
As with many pesticides, species have the ability toevolve and developresistance to pyrethroids. This potential can be mitigated by carefulmanagement. Reports of individual pest species becoming resistant to λ-cyhalothrin[1] are monitored by manufacturers, regulatory bodies such as the EPA and theInsecticide Resistance Action Committee (IRAC).[37] In some cases, the risks of resistance developing can be reduced by using a mixture of two or more insecticides which each have activity on relevant pests but with unrelated mechanisms of action. IRAC assigns insecticides into classes so as to facilitate this. For example,chlorantraniliprole and λ-cyhalothrin are now sold in mixture under the trade name Besiege.[38]
A comprehensive list of brand names for products containing λ-cyhalothrin and γ-cyhalothrin is not available. A brief set for the former are Karate, Kung-fu, Warrior, Cyzmic CS, Demand CS and Foliam. The latter has been sold using names including Bolton, Cobalt, Declare, Proaxis and Scion.
In the United States, Ortho "Home Defense" (for indoor use), Spectracide Bug Stop, Triazicide and Hot Shot are used in the home landscape and garden markets.[39] The Pesticide Properties Database attempts to keep track of the major brands in use.[1]
