 tefluthrin (racemic) | |
| Names | |
|---|---|
| Preferred IUPAC name rac-(2,3,5,6-Tetrafluoro-4-methylphenyl)methyl (1R,3R)-2,2-dimethyl-3-[(1Z)-2-chloro-3,3,3-trifluoroprop-1-en-1-yl]cyclopropane-1-carboxylate | |
| Other names Tefluthrine | |
| Identifiers | |
3D model (JSmol) | |
| ChEBI | |
| ChEMBL | |
| ChemSpider |
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| ECHA InfoCard | 100.124.968 |
| EC Number |
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| KEGG | |
| UNII | |
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| Properties[1] | |
| C17H14ClF7O2 | |
| Molar mass | 418.74 g·mol−1 |
| Appearance | colorless solid |
| Density | 1.48 g/mL |
| Melting point | 44.6 °C |
| Boiling point | 156 °C at 1 mmHg |
| 0.02 mg/L in water >500 g/L in acetone, hexane, toluene | |
| logP | 6.4 |
| Hazards[2] | |
| GHS labelling: | |
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| Danger | |
| H300,H310,H330,H410 | |
| P260,P262,P264,P270,P271,P273,P280,P284,P301+P310,P302+P350,P304+P340,P310,P320,P321,P322,P330,P361,P363,P391,P403+P233,P405,P501 | |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Tefluthrin is theISOcommon name[3] for anorganic compound that is used as apesticide.[1] 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 tefluthrin are often preferred asactive ingredients in agricultural insecticides because they are more cost-effective and longer acting than natural pyrethrins.[4]It is effective against soil pests because it can move as a vapour without irreversibly binding to soil particles: in this respect it differs from most other pyrethroids.[5]
Tefluthrin (X=CH3) is manufactured by theesterification ofcyhalothrin acid chloride[6] with 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol.[7] The latter was a novel compound when tefluthrin was invented[8] and the choice of routes to it has been discussed.[9]
By 1974, a team ofRothamsted Research scientists had discovered three pyrethroids suitable for use inagriculture, namelypermethrin,cypermethrin and deltamethrin.[10] 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, 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 second relied on a process chemists developed to practically manufacture the Z-cis acid by controlling thestereochemistry of the cyclopropane ring in addition to that of the double bond.[6] This led to the commercialisation ofcyhalothrin and made available a relatively large supply of the acid. Exploratory studies continued in which it was combined with a large number of commercially available benzyl alcohols. In the main, these had little or nobiological activity but when penta-fluorobenzyl alcohol was used the ester with X=F not only had substantial intrinsic activity onDiabrotica balteata but continued to be effective when soil was present, in contrast to other known pyrethroids. Further research allowed the analogue with X=CH3 (i.e. what became tefluthrin) to be identified after field trials as the optimum for development under the ICI code number PP993.[5] It was first marketed in 1987 using the trademark Force.[11]In 2000, the agrochemical business of ICI merged with that ofNovartis to formSyngenta, which still manufactures and supplies tefluthrin. The US patent covering the parent compound expired in November 2002.[12]Tefluthrin was registered for sale in the European Union until December 5, 2008, when it was added to a group of pesticides whose authorization was withdrawn and it could no longer be sold.[13] However, on January 1, 2012, it was re-approved for use.[14][15]
Pyrethroid insecticides, including tefluthrin, disrupt the functioning of the nervous system in an organism. They are fast-actingaxonicexcitotoxins, which affect thevoltage-gated sodium channels.[16] The sodium channels are heteromultimeric complexes consisting of one large 𝛼-subunit and two smaller 𝛽-subunits. The binding site of tefluthrin is on the 𝛼-subunit, which also forms the pore of the channel. It alters the functioning of the channel by blocking the inactivation and slowing the deactivation.[17] This results in persistent and prolonged activation of sodium channels and inflow of sodium, which is lethal to the insect. There are many different forms of sodium channels: in mammals, nine different sodium channel 𝛼-subunits have been identified (namedNav1.1-Nav1.9).[18] The channel isoforms differ in affinity for tefluthrin; for example theNav1.6 is at least 15-fold more sensitive than theNav1.2 isoform.[19][20]
Tefluthrin is made available to end-users only informulated products. Its main use is for the control of soil-dwelling insects inmaize when formulated as granules.[21] It can also be incorporated inseed treatments.
All pesticides are required to seekregistration from appropriate authorities in the country in which they will be used.[22] 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).[23] 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 offense.[24] The current (2020) label for tefluthrin in the USA covers its use on field corn, popcorn, seed corn and sweetcorn and specifies the amount to be applied.[25]Within the European Union, a 2-tiered approach is used for theapproval and authorisation of pesticides. Firstly, 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 main use of tefluthrin is to control the larvae of corn rootworms (Diabrotica spp) and it is also lethal tocutworm andwireworm larvae. Related insects share this susceptibility to the compound, including pests such asspringtails,symphylids,millipedes,pygmy beetle,fire ants andwhite grubs.[1] The advantage to the farmer comes in the form of improved yield at harvest. Farmers can act in their best economic interest: the value of the additional yield can be estimated and the total cost of using the insecticide informs the decision to purchase. Thiscost-benefit analysis by the end user sets a maximum price which the supplier can demand. The estimated annual use of tefluthrin in US agriculture is mapped by the US Geological Survey.[26] This shows that use peaked in 2003 but by 2017, the latest date for which figures are available, has fallen to about 150,000 pounds (68,000 kg) annually, almost exclusively in thecorn belt.The ability of tefluthrin to control soil pests, in contrast to other pyrethroids, is due to its relatively highvolatility, which allows its vapour to move from the site of application to the surrounding soil.[5] Its vapour pressure at 20 °C is 8.4 mPa while that of permethrin, for example, is 0.007 mPa.[1]
Tefluthrin is arestricted use pesticide. One consequence of this is that, in the US, 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. It can be absorbed into the body by inhalation of dust or mist and by ingestion. It causes moderate eye irritation. Prolonged or frequently repeated skin contact may cause allergic reactions in some individuals. Skin exposure may result in a transient 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 apparent skin damage.[25]First aid measures are included with the label information.[25]
The mammalianLD50 is 21.8 mg/kg (rats, oral).[1] Phase Imetabolism of tefluthrin proceeds via bothoxidation andhydrolysis.[27]Initial targets for oxidation are its methyl groups. Those on the cyclopropane ring and on the tetrafluorobenzene ring are oxidized to alcohol groups which can be further oxidized into carboxylic acids. Hydrolysis of tefluthrin occurs at the ester bond which results in cyhalothrin acid and 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol, which can be further oxidized into the corresponding carboxylic acid.In phase II metabolism, the phase I metabolites areglucuronidated on any available alcohol groups to facilitate membrane transport and eventually excretion.
Tefluthrin is very highly toxic to freshwater and estuarine fish and invertebrates.[25] Its properties and effects on the environment have been summarized in several publications.[1][2][28]Ultimately it is the regulatory authorities in each country who must weigh up the benefits to end users and balance these against the compound's inherenthazards and consequentrisks to consumers and the wider environment. These authorities stipulate the conditions under which tefluthrin may be used.
Species have the ability toevolve and developresistance to pyrethroids (and, indeed, almost all pesticides). This potential can be mitigated by carefulmanagement. Reports of individual pest species becoming resistant to tefluthrin are monitored by manufacturers, regulatory bodies such as the EPA and theInsecticide Resistance Action Committee (IRAC).[29] 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.
