The prolonged depolarization of the neural membrane is caused by the delayed inactivation of sodium channels, which is the mechanism of λ-Cyhalothrin poisoning. In rat brain synaptosomes, λ-Cyhalothrin induces membrane depolarization, calcium ion influx, and neurotransmitter release [1]. In vitro proliferation of human breast cancer cells is promoted by λ-cyhalothrin, which possesses estrogenic characteristics [1]. Many applications exist for λ-Cyhalothrin in the control of pests (fly, cockroaches, ants, and fleas) [1]. λ-Cyhalothrin is very effective against the Anopheles mosquito, which is the carrier of malaria [1].

Researchers looked examined how lambda-cyhalothrin (i.p.) affected subjects' motor function, memory, and coordination while they were subjected to bilateral carotid artery cross-clamping (BCCA). Neither memory nor motor coordination are hampered by BCCA or lambda-cyhalothrin. A substantial reduction in exploratory motor activity was observed in the BCCA/LCH BCCA/λ-cyhalothrin group. There was a notable decrease in locomotor activity in the BCCA/λ-cyhalothrin group. Over the course of the next two to thirty minutes, mice exposed to lambda-cyhalothrin concurrent with BCCA showed decreased locomotor activity [1].

Absorption, Distribution and Excretion
In rats, following oral admin, cyhalothrin is rapidly eliminated in urine & feces. The ester group is hydrolyzed, both moieties forming polar conjugates.
After twice daily oral ingestion of (14)C-benzyl- or (14)C-cyclopropyl-labelled cyhalothrin (1 mg/kg/day for 7 days), absorption of the insecticide by cows was apparently slow and incomplete. Approximately 50% of the dosed radioactivity was excreted in the feces, mainly as unchanged cyhalothrin, but only small amounts were detected in the bile. With both labelled forms, most of the radioactive material was rapidly eliminated in the urine (27%) and feces (49%) within 24 hr of each daily dose. Only a very small proportion of the dose was secreted in the milk (0.8%) and this was found to be unchanged cyhalothrin. Tissue residues of radioactive material were low and were in the following order: fats> liver> blood> muscle. Residues in fat consisted of unchanged cyhalothrin. The liver and kidney contained small amounts of cyhalothrin, but the residues were largely due to a number of ester-cleavage metabolites that were probably present because the animals were still actively metabolizing and eliminating a significant fraction of the most recent day's intake of cyhalothrin. The almost two-fold difference in the plasma levels of total radiolabelled components obtained with the different labelled forms suggests that little cyhalothrin was present in blood. The ester link must therefore be hydrolysed very rapidly, apart from a small fraction that is distributed into fatty tissues.
The absorption,distribution, excretion, and metabolism of cyhalothrin have been studied in the dog using cyhalothrin labelled either in the acid (14)C-cyclopropyl or alcohol (14)C-benzyl moieties of the molecule. Groups of three male and three female beagle dogs were given a single oral dose of cyhalothrin (1 mg/kg or 10 mg/kg) and, after a 3-week interval, a further single intravenous administration of 0.1 mg/kg. Samples of blood and excreta were collected for 7 days after dosing and were analysed for total radioactivity. The proportions of unchanged cyhalothrin and of metabolites in urine and feces were determined by thin-layer chromatography. The identity of major metabolites was confirmed by mass spectrometry. The absorption of cyhalothrin after oral administration was variable. The degree of absorption was difficult to assess but was within the range 48%-80%. Excretion of radioactivity after both oral and intravenous dosing was initially rapid, with most of the administered radioactivity being excreted in the first 48 hr after dosing. After 7 days, a mean of 82-93% had been excreted.
Groups of six male and six female Alderly Park rats received a single oral dose (1 or 25 mg/kg) of radiolabelled cyhalothrin in corn oil. As it was known that the metabolism of related pyrethroids involves extensive cleavage of the ester bond, duplicate experiments were performed using two forms of cyhalothrin labelled with (14)C in the acid (14)C-cyclopropyl or alcohol (14C-benzyl) portions of the ester. ... Following oral administration of cyhalothrin, absorption was variable but accounted for about 55% of the dose. The proportions absorbed were similar at both dose levels. Excretion was rapid for both (14)C-cyclopropyl- and (14)C-benzyl- labelled cyhalothrin at both dose levels, although excretion rates were faster with the (14)C-benzyl label than with the (14)C-cyclopropyl label. Urinary excretion accounted for approximately 20-40% of the dose and fecal excretion for 40-65% of the dose during the first 7 days. Peak blood concentrations of radioactivity were reached within 4-7 hr, and by 48 hr these concentrations had declined to 10% or less of peak values. A small proportion of an oral dose (2-3%) was retained in the animals after seven days; analysis of twelve different tissues indicated that this radioactivity was present mainly in white fat.
For more Absorption, Distribution and Excretion (Complete) data for CYHALOTHRIN (13 total), please visit the HSDB record page.

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Metabolism / Metabolites
Major metabolic reactions are ester hydrolysis and hydroxylation at the alcohol moiety. The metabolic fates of the alcohol moiety, alpha-cyano-3-phenoxybenzyl alcohol, was the same as those of pyrethroid insecticides having the same alcohol moiety. ... The cyano group of the alcohol moiety of cyhalothrin is expected to undergo conversion to SCN ion. The major metabolites of the acid moiety are cyclopropylcarboxylic acid and its glucuronide and those from the alcohol moiety is PBacid, 4'-OH-PBacid and sulfate of 4'pOH-PBacid.
The comparative metabolism of gamma-cyhalothrin with or without enantiomer pari A and cyhalothrin revealed that enantiomer pair A had little or no effect on the absorption, distribution, tissue retention, or metabolic profiles, implying that enantiomers of cyhalothrin behave independently.
In common with other structurally related pyrethroids, the main routes of metabolism of cyhalothrin in the cow have been found to be similar to those observed in rats and dogs, i.e cleavage of the ester bond with subsequent excretion of the cyclopropyl carboxylic moiety, either free, hydroxylated, or as a glucuronide conjugate. The phenoxybenzyl moiety was further metabolized by loss of the nitrile group and excreted as free 3-phenoxybenzoic acid and its amino acid conjugate, or after aromatic hydroxylation probably at the 4'position. Cyhalothrin itself gives rise to residues in fats; this is consistent with lipophilic properties of cyhalothrin compared to those of its more polar metabolites.
Identification of the metabolites produced in the rat studies revealed that, following oral administration, unabsorbed cyhalothrin was eliminated unchanged via the feces. The absorbed material was rapidly and extensively metabolized and no unchanged cyhalothrin was present in urine or bile. The main route of metabolism was, as anticipated, via hydrolysis of the ester linkage. The cyclopropanecarboxylic acid moiety was subsequently excreted via the urine as the glucuronide conjugate. This material accounted for about 50% of the radioactivity in urine following dosing with (14)C-cyclopropyl-labelled cyhalothrin. The 3-phenoxybenzyl moiety was further metabolized by loss of the nitrile group, oxidation of the aldehyde formed to a carboxylic acid, aromatic hydroxylation at the 4'-position, and formation of the 4-O-sulfate conjugate of 3-(4-hydroxyphenoxy)benzoic acid. This conjugate accounted for approximately 75% of the urinary radioactivity following dosing with (14)C-benzyl-labelled cyhalothrin. No metabolite containing the ester function was detected.
For more Metabolism/Metabolites (Complete) data for CYHALOTHRIN (6 total), please visit the HSDB record page.
Cyhalothrin has been shown to be well absorbed after oral administration, extensively metabolized, and eliminated as polar conjugates in urine. The main route of metabolism is, as anticipated, via hydrolysis of the ester linkage. The cyclopropane-carboxylic acid moiety is subsequently excreted via the urine as the glucuronide conjugate. The 3-phenoxybenzyl moiety is further metabolized by loss of the nitrile group, oxidation of the aldehyde form to a carboxylic acid, aromatic hydroxylation at the 4' position, and formation of the 4- O-sulfate conjugate of 3-(4-hydroxyphenoxy)benzoic acid. (L871)

[1]. Barbara Nieradko-Iwanicka, et al. Effect of Lambda-Cyhalothrin on Memory and Movement in Mice After Transient Incomplete Cerebral Ischemia. Ann Agric Environ Med. 2011;18(1):41-5.

Cyhalothrin is a colorless solid. Insoluble in water. Used as a wide spectrum insecticide.
Cyhalothrin is a carboxylic ester obtained by formal condensation between 3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropanecarboxylic acid and cyano(3-phenoxyphenyl)methanol. It has a role as a pyrethroid ester insecticide, a pyrethroid ester acaricide and an agrochemical. It is an aromatic ether, a nitrile, an organochlorine compound, an organofluorine compound and a cyclopropanecarboxylate ester. It is functionally related to a 3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropanecarboxylic acid.
Cyhalothrin is a synthetic pyrethroid (type 2), used as an insecticide. It is also marketed as Karate. A pyrethroid is a synthetic chemical compound similar to the natural chemical pyrethrins produced by the flowers of pyrethrums (Chrysanthemum cinerariaefolium and C. coccineum). Pyrethroids are common in commercial products such as household insecticides and insect repellents. In the concentrations used in such products, they are generally harmless to human beings but can harm sensitive individuals. They are usually broken apart by sunlight and the atmosphere in one or two days, and do not significantly affect groundwater quality except for being toxic to fish. (L811, L871)

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Mechanism of Action
The synthetic pyrethroids delay closure of the sodium channel, resulting in a sodium tail current that is characterized by a slow influx of sodium during the end of depolarization. Apparently the pyrethroid molecule holds the activation gate in the open position. Pyrethroids with an alpha-cyano group (e.g., fenvalerate) produce more prolonged sodium tail currents than do other pyrethroids (e.g., permethrin, bioresmethrin). The former group of pyrethroids causes more cutaneous sensations than the latter. /Synthetic pyrethroids/
Interaction with sodium channels is not the only mechanism of action proposed for the pyrethroids. Their effects on the CNS have led various workers to suggest actions via antagonism of gamma-aminobutyric acid (GABA)-mediated inhibition, modulation of nicotinic cholinergic transmission, enhancement of noradrenaline release, or actions on calcium ions. Since neurotransmitter specific pharmacological agents offer only poor or partial protection against poisoning, it is unlikely that one of these effects represents the primary mechanism of action of the pyrethroids, & most neurotransmitter release is secondary to incr sodium entry. /Pyrethroids/
The symptoms of pyrethrin poisoning follow the typical pattern ... : (1) excitation, (2) convulsions, (3) paralysis, and (4) death. The effects of pyrethrins on the insect nervous system closely resemble those of DDT, but are apparently much less persistent. Regular, rhythmic, and spontaneous nerve discharges have been observed in insect and crustacean nerve-muscle preparations poisoned with pyrethrins. The primary target of pyrethrins seems to be the ganglia of the insect central nervous system although some pyrethrin-poisoning effect can be observed in isolated legs. /Pyrethrins/
Electrophysiologically, pyrethrins cause repetitive discharges and conduction block. /Pyrethrins/
For more Mechanism of Action (Complete) data for CYHALOTHRIN (10 total), please visit the HSDB record page.

C23H19CLF3NO3

449.85

898.201

91465-08-6

5281873

Viscous liquid yellow-brown

1.33

187-190°C

49.2°C

255.5ºC

1.574

13.088

0

7

7

31

736

0

C(/[C@H]1C(C)(C)[C@H]1C(=O)O[C@H](C1C=CC=C(OC2C=CC=CC=2)C=1)C#N)=C(/Cl)\C(F)(F)F

ZXQYGBMAQZUVMI-UNOMPAQXSA-N

InChI=1S/C23H19ClF3NO3/c1-22(2)17(12-19(24)23(25,26)27)20(22)21(29)31-18(13-28)14-7-6-10-16(11-14)30-15-8-4-3-5-9-15/h3-12,17-18,20H,1-2H3/b19-12-

[cyano-(3-phenoxyphenyl)methyl] 3-[(Z)-2-chloro-3,3,3-trifluoroprop-1-enyl]-2,2-dimethylcyclopropane-1-carboxylate

Karate; Icon; lambda-Cyhalothrin

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~33.33 mg/mL (~74.09 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.56 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)