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, after oral administration of Cyhalothrin, it was rapidly excreted in urine and feces. The ester group was hydrolyzed, and the two parts formed a polar conjugate. In dairy cows, after twice-daily oral administration of (14)C-benzyl or (14)C-cyclopropyl-labeled Cyhalothrin (1 mg/kg/day for 7 consecutive days), absorption of the insecticide was significantly slow and incomplete. Approximately 50% of the radioactive dose was excreted in feces, primarily as unmodified Cyhalothrin, with only trace amounts detected in bile. For both labeled forms of Cyhalothrin, the majority of the radioactive material was rapidly excreted in urine (27%) and feces (49%) within 24 hours of daily administration. Only a very small amount (0.8%) was secreted into milk, and this was found to be unmodified Cyhalothrin. The residual amount of radioactive material in tissues was very low, with the distribution order being: fat > liver > blood > muscle. The residues in fat were unmetabolized Cyhalothrin. Small amounts of Cyhalothrin were found in the liver and kidneys, but these residues primarily originated from various ester bond cleavage metabolites, likely due to the animals still actively metabolizing and eliminating most of the Cyhalothrin ingested in the past day. The difference in total radiolabeled component levels in plasma between different labeled forms of Cyhalothrin was nearly twofold, indicating extremely low levels of Cyhalothrin in the blood. Therefore, except for a small amount distributed to adipose tissue, the ester bonds must be rapidly hydrolyzed. The absorption, distribution, excretion, and metabolism of Cyhalothrin in dogs were investigated using Cyhalothrin labeled at either the acidic (14C-cyclopropyl) or alcoholic (14C-benzyl) moiety. Three male and three female beagle dogs were given a single oral dose of Cyhalothrin (1 mg/kg or 10 mg/kg), followed by a single intravenous injection of 0.1 mg/kg three weeks later. Blood and fecal samples were collected for 7 consecutive days after administration, and total radioactivity was analyzed. The proportion of unmetabolized cyhalothrin and its metabolites in urine and feces was determined by thin-layer chromatography. The identity of the major metabolites was confirmed by mass spectrometry. Individual differences existed in the absorption rate of cyhalothrin after oral administration. The extent of absorption was difficult to assess, but ranged from 48% to 80%. Following both oral and intravenous administration, the excretion of radioactive material was initially rapid, with most of the administered radioactive material being eliminated within 48 hours. After 7 days, an average of 82-93% of the drug was eliminated. Six male and six female Alderly Park rats were administered a single oral dose of 1 or 25 mg/kg of a radiolabeled cyhalothrin corn oil solution. Because the metabolism of pyrethroids is known to involve extensive ester bond cleavage, repeat experiments were conducted using two forms of Cyhalothrin, labeled with either the acidic moiety (14C-cyclopropyl) or the alcoholic moiety (14C-benzyl) of the ester. …After oral administration, the absorption rate of Cyhalothrin varied among individuals, but was approximately 55% of the dose. The absorption rates were similar at both dose levels. At both dose levels, both (14)C-cyclopropyl-labeled and (14)C-benzyl-labeled Cyhalothrin were rapidly excreted, but the (14)C-benzyl-labeled form was excreted faster than the (14)C-cyclopropyl-labeled form. Within the first 7 days, approximately 20-40% of the dose was excreted in urine and approximately 40-65% in feces. Peak concentrations of radioactive substances in the blood are reached within 4–7 hours, and by 48 hours, these concentrations have decreased to 10% or less of the peak. After 7 days, small amounts (2–3%) of the oral dose remain in the animals. Analysis of twelve different tissues showed that this radioactivity is primarily found in white fat. For more complete data on the absorption, distribution, and excretion of Cyhalothrin (13 in total), please visit the HSDB record page. Metabolism/Metabolites: The main metabolic reactions are ester hydrolysis and hydroxylation of the alcohol moiety. The metabolic pathway of the alcohol moiety (α-cyano-3-phenoxybenzyl alcohol) is the same as that of pyrethroid insecticides with the same alcohol moiety. …It is expected that the cyano group of the Cyhalothrin alcohol moiety will be converted to SCN ions. The main metabolites of the acidic moiety are cyclopropylcarboxylic acid and its glucuronide, while the main metabolites of the alcohol moiety are sulfates of PBacid, 4'-OH-PBacid, and 4'-pOH-PBacid. Comparative studies of the metabolism of γ-Cyhalothrin and its enantiomers showed that enantiomer A had almost no effect on the absorption, distribution, tissue retention, or metabolite profile of Cyhalothrin, indicating that the enantiomers of Cyhalothrin function independently. Like other structure-related pyrethroid insecticides, the main metabolic pathway of Cyhalothrin in cattle is similar to that observed in rats and dogs, involving ester bond cleavage followed by excretion in free, hydroxylated, or glucuronide conjugate forms. The phenoxybenzyl moiety is further metabolized, excreted via the loss of a nitrile group as free 3-phenoxybenzoic acid and its amino acid conjugate, or possibly after aromatic hydroxylation at the 4' position. Cyhalothrin itself remains in fats; this is consistent with the lipophilicity of Cyhalothrin relative to its more polar metabolites. Identification of metabolites produced in rat studies showed that unabsorbed Cyhalothrin was excreted unchanged in feces after oral administration. The absorbed substance is rapidly and extensively metabolized, and unchanged Cyhalothrin was not detected in urine or bile. As expected, the primary metabolic pathway is via ester bond hydrolysis. The cyclopropane carboxylic acid moiety is subsequently excreted in urine as a glucuronide conjugate. This substance accounts for approximately 50% of urinary radioactivity after administration of 14C-cyclopropyl-labeled Cyhalothrin. The 3-phenoxybenzyl moiety is further metabolized, including the loss of the nitrile group, oxidation of the resulting aldehyde to a carboxylic acid, 4'-aromatic hydroxylation, and formation of a 4-O-sulfate conjugate of 3-(4-hydroxyphenoxy)benzoic acid. This conjugate accounts for approximately 75% of urinary radioactivity after administration of 14C-benzyl-labeled Cyhalothrin. No metabolites containing ester groups were detected. For more complete data on the metabolism/metabolites of Cyhalothrin (6 in total), please visit the HSDB record page. Studies have shown that oral Cyhalothrin is well absorbed, extensively metabolized, and excreted in the urine as a polar conjugate. As expected, its primary metabolic pathway is via ester bond hydrolysis. The cyclopropane carboxylic acid moiety is subsequently excreted in the urine as a glucuronide conjugate. The 3-phenoxybenzyl moiety is further metabolized, including the removal of the nitrile group, aldehyde oxidation to carboxylic acid, 4'-aromatic hydroxylation, and the formation of a 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 broad-spectrum insecticide. Cyhalothrin is a carboxylic acid ester formed by the condensation of 3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropanecarboxylic acid with cyano(3-phenoxyphenyl)methanol. It is a pyrethroid insecticide, pyrethroid acaricide, and agricultural chemical. It is an aromatic ether, nitrile, organochlorine compound, organofluorine compound, and cyclopropanecarboxylic acid ester. Its functional group is related to 3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropanecarboxylic acid. Cyhalothrin is a synthetic pyrethroid (type II) used as an insecticide. It is also marketed under the trade name "Karate". Pyrethroids are synthetic compounds whose structures are similar to those of the natural pyrethroids produced by the flowers of plants in the genus Pyrethrum (such as Grewia chinensis and Chrysanthemum indicum). Pyrethroids are commonly found in commercial products such as household insecticides and repellents. At the concentrations used in these products, they are generally harmless to humans but may cause harm to sensitive populations. They typically decompose within one or two days in sunlight and the atmosphere, and do not significantly affect groundwater quality except for their toxicity to fish. (L811, L871)

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Mechanism of Action
Synthetic pyrethroids delay the closure of sodium channels, thus generating a sodium tail current, characterized by the slow influx of sodium ions at the end of depolarization. Clearly, the pyrethroid molecule keeps the activation gate open. Pyrethroids containing α-cyano groups (such as Cyhalothrin) produce a more persistent sodium tail current than other pyrethroids (such as permethrin and bio-permethrin). The former type of pyrethroid is more likely to cause dermal paresthesia than the latter. /Synthetic Pyrethroids/
Interaction with sodium channels is not the only mechanism of action of pyrethroids. Their effects on the central nervous system have led many researchers to propose that their mechanisms of action may include antagonism of γ-aminobutyric acid (GABA)-mediated inhibition, regulation of nicotinic cholinergic transmission, enhancement of norepinephrine release, or action on calcium ions. Since the protective effect of neurotransmitter-specific drugs against poisoning is limited or incomplete, these effects are unlikely to be the main mechanisms of action of pyrethroids, and most neurotransmitter release is secondary to an increase in sodium ion influx. Pyrethroids/
Symptoms of pyrethroid poisoning follow a typical pattern: (1) excitation, (2) convulsions, (3) paralysis, (4) death. The effects of pyrethroids on the insect nervous system are very similar to those of DDT, but the duration is significantly shorter. Regular, rhythmic, and spontaneous neural discharges have been observed in neuromuscular specimens of insects and crustaceans poisoned with pyrethroids. The primary targets of pyrethroids appear to be ganglia of the insect central nervous system, although some pyrethroid toxicity effects have also been observed in detached legs. /Pyrethroids/
From an electrophysiological perspective, pyrethroids cause repetitive discharges and conduction block. /Pyrethroids/
For more complete data on the mechanisms of action of Cyhalothrins (10 species), 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.)