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Cyfluthrin (0-50 μM; 24 hours) inhibits the proliferation of SH-SY5Y cells growth with an IC50 and an IC30 of 19.39 μM and 4.81 μM, respectively[1].

Absorption, Distribution and Excretion
Nine male volunteers were exposed to the pyrethroid insecticide cyfluthrin. The study was performed in an exposure room, where an aerosol containing cyfluthrin was sprayed to obtain atmospheres with mean cyfluthrin concentrations of 160 and 40 ug/cu m. Four volunteers were exposed for 10, 30 and 60 min at 160 ug/cu m and another five volunteers were exposed for 60 min at 40 ug/cu m. For 160 ug/cu m exposure urine samples were collected before and immediately after exposure as well as for the periods 1-2, 2-3, 3-4, 4-5, 5-6, 6-12 and 12-24 hr after exposure. For 40 ug/cu m exposure urine samples were collected before and 2 hr after exposure. ... Of the metabolites, 93% was excreted within the first 24 hr (peak excretion rates between 0.5 and 3 hr) after inhalative exposure of 160 ug/cu m. ... The amount of metabolites in urine depends on the applied dose, on the exposure time and shows interindividual differences.
14C derived from the alcohol moiety was rapidly and completely excreted into urine and feces after single oral administration of 14C-alcohol labeled preparation to rats at 0.5 and 10 mg/kg, 55-70 and 25-35% of the dose being excreted into urine and feces, respectively. Excretion of 14C into bile was about 34%. The fat and sciatic nerve showed relatively higher 14C tissue residues.
The influence of the formulation vehicle on the rate of absorption of cyfluthrin was studied in groups of 14 fasted male Wistar rats given single doses by gavage of 10 mg/kg bw dissolved in either polyethylene glycol (PEG) 400 or a Cremophor EL:water emulsion. Two rats from each group were killed 0.5, 1, 2, 4, 6, 16, and 24 hr after treatment. The concentrations of cyfluthrin and its respective enantiomers were determined in the blood and stomach. When the compound was emulsified in the Cremophor EL:water solution, absorption was rapid; the cis isomer was that most frequently detected within 30 min after treatment. Maximum peak blood concentrations occurred within 1 hr of treatment. Cyfluthrin emulsified in PEG 400 was not detected until 4 hr after administration, and peak blood levels were observed only 6 hr after treatment. Examination of the stomach contents revealed a larger quantity of cyfluthrin in the stomachs of rats treated with the drug in a PEG 400 emulsion
Four groups of 30 male and 24 female Mura:SPRA (SPF 68 Han) rats received 14C-radiolabelled cyfluthrin as either oral doses of 0.5 or 10 mg/kg bw or iv or intraduodenal doses of 0.5 mg/kg bw. Another group received unlabelled cyfluthrin orally once a day for 14 consecutive days, followed by a single oral dose of 0.5 mg/kg bw 14C-cyfluthrin. Excreta, organs, tissues, and blood samples were collected at several intervals and assayed for radiolabel. After oral administration by any schedule, up to 80% of the labelled cyfluthrin was effectively absorbed by females and about 90% by males. ... Less than 2% of radiolabelled drug was present 48 hr after oral administration. No significant pulmonary excretion pathway exists, as < 0.001% was detected in the expired gaseous phase as 14CO21. About 98-99% of the orally administered dose was readily available for renal and fecal excretion ... . Males excreted two to three times more in the urine than in the feces, whereas the renal:fecal excretion ratio in females was 1.2-1.7:1 after oral administration. Consequently, the area under the curve (AUC) is two times larger for females than males. Forty-eight hours after the iv injection, 93-95% of the dose was excreted, with a renal:fecal excretion ratio of 2.9:1 in males and 2.3:1 in females. Therefore, excretion depends somewhat on the route of administration and on sex. ... The residues found in the organs and tissues were influenced by the route of administration, as the mean relative concentration of cyfluthrin in the bodies of males and females at sacrifice was lower after oral administration (0.013) than after intravenous injection (0.06). Female rats had higher plasma concentrations after oral administration of the single high or low dose; 48 hr after administration, lower concentrations were detected in the bone and muscle of animals of each sex and in the testes of males rats. The sciatic nerve showed a similar relative concentration value, which may explain the toxic effects observed on the peripheral nervous system. Higher concentrations were detected in the spleen, adrenal glands, liver, and plasma of both males and females and in the ovaries. The renal fatty tissue concentration was about seven times higher after either oral or intravenous administration, whereas the mean concentration in brain was significantly lower ( p = 0.0006-0.006)...
For more Absorption, Distribution and Excretion (Complete) data for CYFLUTHRIN (9 total), please visit the HSDB record page.

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Metabolism / Metabolites
Nine male volunteers were exposed to the pyrethroid insecticide cyfluthrin. ... The main urinary cyfluthrin metabolites, cis-/trans-3-(2,2-dichlorovinyl)-2,2-dimethylycyclopropane carboxylic acid (DCCA) and 4-fluoro-3-phenoxybenzoic acid (FPBA), were determined. The limit of detection (LOD) for all metabolites was 0.0025 ug in an urine sample of 5 mL (0.5 ug/L). After inhalative exposure of 40 ug cyfluthrin/cu m air for 60 min, the amount of metabolites in urine collected in the first 2 hr after exposure was less than the LOD, namely 0.14 ug for cis-DCCA, 0.15-0.28 ug for trans-DCCA and 0.12-0.23 ug for FPBA. Of the metabolites, 93% was excreted within the first 24 hr (peak excretion rates between 0.5 and 3 hr) after inhalative exposure of 160 ug/cu m. ... The amount of metabolites in urine depends on the applied dose, on the exposure time and shows interindividual differences.
Eight hours after oral administration of 14C-labelled cyfluthrin at a dose of 10 mg/kg bw to three male Sprague-Dawley rats, about 60% of the labelled cyfluthrin was eliminated in the urine in conjugated forms. Conjugates of 4'-hydroxy-3-phenoxyfluorobenzoic acid (50%) were identified; a second major metabolite was identified after hydrochloric acid hydrolysis as a conjugate of 3-phenoxy-4-fluorohippuric acid (40%). These metabolites represented 33 and 27% of the administered radiolabel, respectively. A glycine conjugate constituted 2.5% of the conjugated metabolites.
In another study ... , four groups of five male and five female rats received 14C-cyfluthrin ... . The initial step in cyfluthrin biotransformation was ester hydrolysis, giving a 3-phenoxy-4-fluorobenzyl alcohol intermediate and the permethric acid fraction. The metabolism of permethric acid has been well established in the rat in studies with chemically similar pyrethroids. After ester hydrolysis, the 3-phenoxy-4-fluorobenzyl alcohol moiety was oxidized to the free metabolite 3-phenoxy-4-fluorobenzoic acid. This metabolite can then either be conjugated with glycine to form 3-phenoxy-4-fluorohippuric acid (a minor metabolite constituting < 3% of the recovered urinary radiolabel, dependent on neither sex nor dose) or hydroxylated to give 4'-hydroxy-3-phenoxy-4-fluorobenzoic acid (conjugates of which account for 41-50% of the total urinary radiolabel recovered from rats given one or multiple doses of cyfluthrin at 0.5 mg/kg bw). Females tended to excrete more of this metabolite as the free form in the faeces than did males. Males and females at the high dose (10 mg/kg bw) excreted about 35% of the administered dose as conjugates of 4'-hydroxy-3-phenoxy-4-fluorobenzoic acid, whereas females excreted about 5% more than males as the free metabolite. After repeated oral doses of 0.5 mg/kg bw for 14 days, 12-16% of labelled metabolite was found in the faeces as cyfluthrin, whereas < 1% was found when single oral doses were administered. After a single high dose of 10 mg/kg bw, 17-19% was recovered in the faeces as parent compound. The authors concluded that the metabolism of cyfluthrin is slightly dose-dependent.
The metabolic pathways for the breakdown of the pyrethroids vary little between mammalian species but vary somewhat with structure. ... Essentially, pyrethrum and allethrin are broken down mainly by oxidation of the isobutenyl side chain of the acid moiety and of the unsaturated side chain of the alcohol moiety with ester hydrolysis playing and important part, whereas for the other pyrethroids ester hydrolysis predominates. /Pyrethrum and pyrethroids/
For more Metabolism/Metabolites (Complete) data for CYFLUTHRIN (8 total), please visit the HSDB record page.
The initial step in cyfluthrin biotransformation is ester hydrolysis, giving a 3-phenoxy-4-fluorobenzyl alcohol intermediate and the permethric acid fraction. After ester hydrolysis, the 3-phenoxy-4-fluorobenzyl alcohol moiety is oxidized to the free metabolite 3-phenoxy-4-fluorobenzoic acid. This metabolite can then either be conjugated with glycine to form 3-phenoxy-4-fluorohippuric acid or hydroxylated to give 4'-hydroxy-3-phenoxy-4-fluorobenzoic acid. The metabolites as well as a small pert of the unmetabolized compound are excreted in the urine in the feces. (L857, A562)

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Biological Half-Life
Nine male volunteers were exposed to the pyrethroid insecticide cyfluthrin. ... The mean half-lives were 6.9 hr for cis-3-(2,2-dichlorovinyl)-2,2-dimethylycyclopropane carboxylic acid (cis-DCCA), 6.2 hr for trans- 3-(2,2-dichlorovinyl)-2,2-dimethylycyclopropane carboxylic acid (trans-DCCA) and 5.3 hr for 4-fluoro-3-phenoxybenzoic acid. The mean trans-:cis-DCCA ratio was 1.9 for the time course as well as for each subject. ...
... A cyfluthrin elimination experiment showed that cyfluthrin metabolites are eliminated following first-order kinetics (t 1/2 = 6.4 hr )...

Toxicity Summary
Both type I and type II pyrethroids exert their effect by prolonging the open phase of the sodium channel gates when a nerve cell is excited. They appear to bind to the membrane lipid phase in the immediate vicinity of the sodium channel, thus modifying the channel kinetics. This blocks the closing of the sodium gates in the nerves, and thus prolongs the return of the membrane potential to its resting state. The repetitive (sensory, motor) neuronal discharge and a prolonged negative afterpotential produces effects quite similar to those produced by DDT, leading to hyperactivity of the nervous system which can result in paralysis and/or death. Other mechanisms of action of pyrethroids include antagonism of gamma-aminobutyric acid (GABA)-mediated inhibition, modulation of nicotinic cholinergic transmission, enhancement of noradrenaline release, and actions on calcium ions. They also inhibit calium channels and Ca2+, Mg2+-ATPase. (T10, T18, L857)

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Toxicity Data
LD50: 869-1271 mg/kg (Oral, Rat) (L862)
LD50: 291-609 mg/kg (Oral, Mouse) (L862)
L50: > 5000 mg/kg (Dermal, Rat) (L862)

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Interactions
/Pyrethroid/ detoxification ... important in flies, may be delayed by the addition of synergists ... organophosphates or carbamates ... to guarantee a lethal effect. ... /Pyrethroid/
Piperonyl butoxide potentiates /insecticidal activity/ of pyrethrins by inhibiting the hydrolytic enzymes responsible for pyrethrins' metabolism in arthropods. When piperonyl butoxide is combined with pyrethrins, the insecticidal activity of the latter drug is increased 2-12 times /Pyrethrins/
At dietary level of 1000 ppm pyrethrins & 10000 ppm piperonyl butoxide ... /enlargement, margination, & cytoplasmic inclusions in liver cells of rats/ were well developed in only 8 days, but ... were not maximal. Changes were proportional to dosage & similar to those produced by DDT. Effects of the 2 ... were additive. /Pyrethrins/

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Non-Human Toxicity Values
LD50 Rat male oral 500-800 mg/kg, and in female rat 1,200 mg/kg
LD50 Mouse male oral 300 mg/kg, and in female mouse 600 mg/kg
LD50 Rat oral 500 mg/kg (in polyethyleneglycol)
LD50 Rat oral 270 mg/kg (in xylene)
For more Non-Human Toxicity Values (Complete) data for CYFLUTHRIN (9 total), please visit the HSDB record page.

[1]. Jin-Sung Choi,et al.Structure-activity Relationships for the Action of 11 Pyrethroid Insecticides on Rat Na v 1.8 Sodium Channels Expressed in Xenopus Oocytes.Toxicol Appl Pharmacol. 2006 Mar 15;211(3):233-44
[2]. María-Aránzazu Martínez, et al. Oxidative Stress and Related Gene Expression Effects of Cyfluthrin in Human Neuroblastoma SH-SY5Y Cells: Protective Effect of Melatonin. Environ Res. 2019 Oct;177:108579.

Cyfluthrin appears as a viscous amber partly crystalline oil. Used as an insecticide.
Cyfluthrin is a carboxylic ester obtained by formal condensation between 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylic acid and (4-fluoro-3-phenoxyphenyl)(hydroxy)acetonitrile. It has a role as a pyrethroid ester insecticide and an agrochemical. It is an organochlorine compound, an organofluorine compound, a nitrile, an aromatic ether and a cyclopropanecarboxylate ester. It is functionally related to a 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid.
Cyfluthrin is a synthetic (type 2) pyrethroid insecticide that has both contact and stomach poison action. It is a non-systemic chemical used to control cutworms, ants, silverfish, cockroaches, termites, grain beetles, weevils, mosquitoes, fleas, flies, corn earworms, tobacco budworm, codling moth, European corn borer, cabbageworm, loopers, armyworms, boll weevil, alfalfa weevil, Colorado potato beetle, and many others. Its primary agricultural uses have been for control of chewing and sucking insects on crops such as cotton, turf, ornamentals, hops, cereal, corn, deciduous fruit, peanuts, potatoes, and other vegetables. Cyfluthrin is also used in public health situations and for structural pest control. (L862)

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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 central nervous system 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 partical protection against poisoning, it is unlikely that one of these effects represents the primary mechanism of action of the pyrethroids, and most neurotransmitter release is secondary to increased sodium entry. /Pyrethroids/
... Type II pyrethroids are a group of insecticides largely used in agriculture and public health. The nervous system is the main target for pyrethroids in insects and mammals. One notable form of toxicity associated with over exposure has been a facial cutaneous paraesthesia and irritation-related respiration symptoms including behavioral excitation mainly observed in workers spraying pyrethroids or in occupational settings. In acutely exposed rats, type II pyrethroids produce a severe syndrome characterized by salivation and choreoathetosis. Because many of the acute functional effects of type II pyrethoids can be associated with the neurotoxic effect on 5-hydroxytryptamine (5-HT) neurones, the objective of the present study was to examine whether deltamethrin, cyfluthrin and lambda-cyhalothrin administration results in changes of 5-HT content in rat brain. ... Rats were injected with either corn oil or pyrethroids (deltamethrin, 20 mg/kg per day, ip, for 6 days; cyfluthrin, 14 mg/kg per day, ip, for 6 days; lambda-cyhalothrin, 8 mg/kg per day, ip, for 6 days). The frontal cortex, hippocampus, midbrain and striatum were removed at 24 hours post treatment and were analysed for content of 5-HT and 5-HIAA using a HPLC method with electrochemical detection. ... A serotonin depleting effect was produced by these type II pyrethroids. The concentration of 5-HT and its metabolite 5-HIAA decreased in the brain regions from pyrethroid treated animals. Pyrethroids accelerated the turnover of 5-HT in midbrain and striatum areas. It is concluded that pyrethroids affect serotonin neurotransmission.
... Since the type II pyrethroids deltamethrin and cypermethrin, but not the type I pyrethroid cismethrin act on chloride channels, this could contribute to the bimodal nature of pyrethroid poisoning syndromes. ... Excised inside-out membrane patches from differentiated mouse neuroblastoma cells were used, and mean channel open probabilities calculated. For single dosing at 10 uM, bioallethrin, beta-cyfluthrin, cypermethrin, deltamethrin, and fenpropathrin were all found to significantly decrease open channel probability (p < 0.05). Bifenthrin, bioresmethrin, cispermethrin, cisresmethrin, cyfluthrin isomers 2 and 4, lambda-cyhalothrin, esfenvalerate, and tefluthrin, did not significantly alter open channel probability (p > 0.05). Since the type II pyrethroids, esfenvalerate, and lambda-cyhalothrin were ineffective, /one/ must conclude that actions at the chloride ion channel target cannot in themselves account for the differences between the two types of poisoning syndrome. Sequential dosing with type II pyrethroids caused no further chloride ion channel closure. The type I pyrethroid cisresmethrin did however prevent a subsequent effect by the mixed type pyrethroid fenpropathrin. In contrast, the type I pyrethroid cispermethrin did not prevent a subsequent effect due to the type II pyrethroid deltamethrin. The difference in effect may be the result of differences in potency, as deltamethrin had a greater effect than fenpropathrin. It therefore appears clear that in some combinations the type I and type II pyrethroids can compete and may bind to the same chloride channel target site.
For more Mechanism of Action (Complete) data for CYFLUTHRIN (7 total), please visit the HSDB record page.

C22H18CL2FNO3

434.28762

433.064

68359-37-5

104926

Yellowish-brown oil
Colorless crystals

1.4±0.1 g/cm3

496.3±45.0 °C at 760 mmHg

60ºC

253.9±28.7 °C

0.0±1.3 mmHg at 25°C

1.611

6.29

0

5

7

29

679

0

CC1(C)C(C=C(Cl)Cl)C1C(=O)OC(C#N)C2=CC(=C(C=C2)F)OC3=CC=CC=C3

QQODLKZGRKWIFG-UHFFFAOYSA-N

InChI=1S/C22H18Cl2FNO3/c1-22(2)15(11-19(23)24)20(22)21(27)29-18(12-26)13-8-9-16(25)17(10-13)28-14-6-4-3-5-7-14/h3-11,15,18,20H,1-2H3

[cyano-(4-fluoro-3-phenoxyphenyl)methyl] 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carboxylate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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