Absorption, Distribution and Excretion
1. Dose-excretion studies were conducted on cypermethrin (as a 1:1 mixture of cis and trans isomers) and α-cypermethrin (one of the two trans isomers of cis-cypermethrin), with two volunteers enrolled at each dose level. The studies included: (a) a single oral dose of 0.25 mg, 0.50 mg, and 0.75 mg of α-cypermethrin, followed by repeated daily doses for five consecutive days; (b) repeated daily oral doses of 0.25 mg, 0.75 mg, and 1.5 mg of cypermethrin for five consecutive days; and (c) a single topical application of 25 mg of cypermethrin to the forearm. The concentrations of free and bound 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid in urine were monitored before and after administration. 2. The metabolism and excretion rates of a single oral dose of α-cypermethrin were similar to those of cis-cypermethrin; on average, 43% of the dose was excreted in the urine as cyclopropane carboxylic acid within 24 hours after administration. Repeated oral administration of α-cypermethrin did not increase the excretion of metabolites in the urine. Subjects excreted an average of 49% of the dose as cyclopropane carboxylic acid within the subsequent 24 hours after administration. 3. Repeated oral administration of cypermethrin did not increase the excretion of cyclopropane carboxylic acid in the urine. Subjects excreted an average of 72% of the trans isomer dose and 45% of the cis isomer dose, respectively, within 24 hours after administration. 4. Approximately 0.1% of 25 mg of cypermethrin administered transdermally was excreted in the urine as cyclopropane carboxylic acid within 72 hours. Based on the urinary excretion data, no conclusions can be drawn regarding the concentrations of cypermethrin and its metabolites in the skin or other organs, or whether other metabolic or excretion pathways exist.
/Pyrethroids/ Topical LD50 shows their easy penetration of insect epidermis (e.g., cockroaches).../Pyrethroids/
When radioactive pyrethroids are administered orally to mammals, they are absorbed into the animal's intestines and distributed to all tested tissues. Excretion of radioactive material in rats after administration of the trans isomer: Dose: 500 mg/kg; 20-day interval; urine 36%; feces 64%; total 100%./Pyrethroids/
When applied topically, pyrethroids can be absorbed through intact skin. When animals are exposed to aerosols containing pyrethroids and synergistic ethers, little or no systemic absorption of the mixture is observed./Pyrethroids/
While limited absorption may be the reason for the lower toxicity of some pyrethroids, rapid biodegradation by mammalian liver enzymes (ester hydrolysis and oxidation) is likely a major factor. Most pyrethroid metabolites are rapidly excreted, at least partially, via the kidneys. /Pyrethroids/
Male and female rats were administered a single oral dose of (14)C-(1RS)-trans- and (1RS)-cis-cypermethrin labeled with benzyl ring, cyclopropane ring, or CN group at doses of 1–5 mg/kg. Results showed that the C-14 of the acid and alcohol groups was rapidly and almost completely excreted from urine and feces. The C-14 of the CN group was excreted relatively slowly from urine and feces, with an overall recovery rate of 50–67%. Except for adipose tissue (approximately 1 ppm), residual amounts in rat tissues treated with the acid or alcohol-labeled formulations were generally very low. In contrast, the CN-labeled formulations showed relatively high residual levels, particularly in the stomach (contents), intestines, and skin.
At spray doses up to 46 mg/h, approximately 3% of cypermethrin was absorbed through the skin after exposure.
This study investigated exposure to and absorption of cypermethrin when sprayed in ultra-low volume formulations in the air. At two commercial cotton farms in Mississippi, one contract pilot and one blender/loader were monitored for skin exposure to cypermethrin during 12 aerial spraying operations. Each operation consisted of one blending/loading maneuver and one spraying of 50 gallons of diluted spray solution, lasting approximately 30 minutes. Three volunteer blenders/loaders collected all their urine samples from 1 or 2 days prior to exposure to 24 hours within 6 days post-exposure. Cypermethrin uptake was assessed by measuring urinary metabolites. All blenders/loaders wore protective equipment. Potential and actual total skin exposures were estimated. The mean potential exposure (protected skin and exposed skin) for the pilot and blender/loader were 1.07 mg/8 hours/day and 10.5 mg/day, respectively. The mean actual skin exposures for the pilot and blender/loader were 0.67 mg/day and 2.43 mg/day, respectively. 67% of the pilot's total potential exposure occurred in the hands. Exposure to the mixing/loading personnel primarily involved the arms, torso, and hands, accounting for 37%, 24%, and 17% of total exposure, respectively. Analysis of urinary metabolites determined that the absorption by mixing/loading personnel ranged from 46 to 78 micrograms of cypermethrin equivalent per 3 mixed loads and per 12 simulated mixed loads. The conclusion is that exposure to both pilots and mixing/loading personnel is extremely low during ultra-low volume aerial spraying operations. Only a small amount of cypermethrin absorbed through skin contact is absorbed.
1. Dose-excretion studies were conducted using cypermethrin (a 1:1 cis-trans mixture) and α-cypermethrin (one of the two trans isomers constituting cis-cypermethrin), with two volunteers participating at each dose level. The study included: (a) a single oral dose of 0.25 mg, 0.50 mg, and 0.75 mg of α-cypermethrin, followed by repeated daily doses for 5 consecutive days; (b) repeated daily oral doses of 0.25 mg, 0.75 mg, and 1.5 mg of cypermethrin for 5 consecutive days; and (c) a single topical application of 25 mg of cypermethrin to the forearm. The concentrations of free and bound 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid in urine were monitored before and after administration. 2. The metabolism and excretion rates of a single oral dose of α-cypermethrin were similar to those of cis-cypermethrin, with an average of 43% of the dose excreted as cyclopropanecarboxylic acid within 24 hours after administration. Repeated oral administration of α-cypermethrin did not increase the excretion of metabolites in urine. Within 24 hours following administration, an average of 49% of the dose was excreted as cyclopropanecarboxylic acid in the subjects. 3. Repeated oral administration of cypermethrin did not increase the excretion of cyclopropanecarboxylic acid in urine. Subjects excreted an average of 72% of the trans isomer and 45% of the cis isomer dose within 24 hours of administration. 4. Approximately 0.1% of 25 mg cypermethrin administered transdermally was excreted as cyclopropanecarboxylic acid in urine within 72 hours. These urinary excretion data cannot be used to draw conclusions about the concentrations of cypermethrin and its metabolites in the skin or other organs, or whether other metabolic or excretion pathways exist.
For more complete data on the absorption, distribution, and excretion of cypermethrin (9 species), please visit the HSDB records page.

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Metabolism/Metabolites
The metabolic pathways of pyrethroids do not differ significantly among different mammalian species, but may vary slightly depending on structure. ...Essentially, pyrethroids and allethrin are primarily decomposed through the oxidation of the isobutylene side chain of the acid moiety and the unsaturated side chain of the alcohol moiety, with ester hydrolysis also playing a significant role; while other pyrethroids are mainly decomposed through ester hydrolysis. /Pyrethroids and Pyrethroids/
The relative resistance of mammals to pyrethroids is almost entirely attributed to their ability to rapidly hydrolyze pyrethroids into inactive acid and alcohol components, as direct injection into the mammalian central nervous system results in sensitivity similar to that of insects. Partial additional resistance in homeothermic organisms can also be attributed to the negative temperature coefficient of pyrethroids, resulting in lower toxicity at mammalian body temperature, but the primary mechanism of action is metabolic. Pyrethroids are metabolized and cleared very quickly, meaning that intravenous injection results in high toxicity, oral absorption in moderately slow toxicity, and skin absorption in typically unmeasurable toxicity. /Pyrethroids/
Primary alcohol esters of trans-substituted acids decompose the fastest due to their rapid hydrolysis and oxidation. For all secondary alcohol esters and primary alcohols of cis-substituted cyclopropane carboxylic acids, oxidation is dominant. /Pyrethroids/
Pyrethroids are reported to be inactivated in the gastrointestinal tract after ingestion. In animals, pyrethroids are rapidly metabolized into water-soluble, inactive compounds. Pyrethroids/
Synthetic pyrethroid insecticides are generally metabolized in mammals via ester hydrolysis, oxidation, and conjugation, and do not accumulate in tissues. In the environment, synthetic pyrethroid insecticides degrade relatively quickly in soil and plants. Ester hydrolysis and oxidation at different sites on the molecule are the main degradation processes. /Synthetic Pyrethroids/
For cypermethrin, esterase attack is more important than oxidative attack than for permethrin; in the mouse system, the ratio of esterase attack to oxidative attack for trans-cypermethrin was 93.2% vs. 17.3%, and for cis-cypermethrin it was 41.5% vs. 37.6%. For deltamethrin, which is only the cis isomer, the ratio of esterase attack to oxidative attack was 28.3% to 41%. Given the higher oxidation rate observed in the mouse system, these data suggest that esterase metabolism in these pyrethroids is at least as important as oxidative metabolism. The primary degradation pathway of deltamethrin is ester bond hydrolysis, ultimately yielding 3-phenoxybenzoic acid and 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid. (The cis isomer yields both cis and trans-cyclopropanecarboxylic acids.) The secondary degradation pathway is cyclohydroxylation to α-cyano-3-(4-hydroxyphenyl)benzyl ester, followed by hydrolysis to the corresponding hydroxycarboxylic acid. Following administration to rats and mice, most of the trans-deltamethrin was excreted in the urine within 24 hours. Under similar conditions, 80% of the 3-phenoxybenzoic acid was excreted. Following administration of cis-deltamethrin, the amount excreted in feces increased. Using mass spectrometry and nuclear magnetic resonance (NMR), the major metabolite of trans-cypermethrin and 3-phenoxybenzoic acid in mouse urine was identified as N-(3-phenoxybenzoyl)taurine. The minor metabolite was sulfate of 3-(4-hydroxyphenoxy)benzoic acid. Taurine conjugates were not detected in rat urine. In rats, the major metabolite was sulfate conjugate of 3-(4-hydroxyphenoxy)benzoic acid. Mouse liver microsomes with NADPH preparations hydroxylated the tert-methyl and cyclic methyl groups of trans- and cis-cypermethrin, as well as the 4' and 5-positions. Hydroxylation at the 5-position of trans-cypermethrin was only detected in microsomes treated with tetraethyl pyrophosphate to inhibit esterase activity. The major metabolic reactions of trans- and cis-cypermethrin included ester bond cleavage, oxidation of the trans- and cis-methylcyclopropane rings and the phenoxy group at the 4' position, and conversion of the cyano group to a thiocyanate ion. The following subtle interspecies differences were observed: (1) oxidation at positions 5 and 6 of the alcohol moiety was observed in mice but not in rats; (2) ester metabolites such as 2'-OH, 5-OH, and trans-OH,4'-OH-cypermethrin were detected in mouse feces but not in rat feces. A significant interspecies difference in metabolites was found in the PBacid-taurine conjugate, the major metabolite in mice but not in rats. More complete metabolite/metabolite data for cypermethrin (9 metabolites in total) can be found on the HSDB record page. Studies have shown that oral cypermethrin 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 (L857).

Toxicity Summary
Product Characteristics: Cypermethrin is a highly effective pyrethroid insecticide, effectively controlling a variety of common pests in agriculture and livestock. It is available in emulsifiable concentrates, ultra-low volume formulations, suspension concentrates, and mixtures with other insecticides. The technical grade is a crystalline powder, readily soluble in acetone, cyclohexanone, and xylene, but with low water solubility. It is stable under acidic and neutral conditions. Human Exposure: The risk of exposure to cypermethrin in the general population is negligible when used according to good agricultural practices. Good work practices, hygiene measures, and safety precautions make occupational exposure to cypermethrin unlikely. Facial discomfort may indicate exposure to cypermethrin. In such cases, work practices should be reviewed. Animal Studies: Cypermethrin exhibits moderate to high acute oral toxicity in rodents. Acute oral exposure can lead to clinical symptoms related to central nervous system activity. Technical grade cypermethrin has been reported to have minimal skin irritation in rabbits. Some formulations can cause severe eye irritation. In guinea pigs, α-cypermethrin can stimulate sensory nerve endings in the skin. An oral study in rats showed that α-cypermethrin can cause neurotoxicity, manifested as histopathological changes, axonal degeneration, and increased β-galactosidase activity in the tibial and sciatic nerves. Currently, there are no data on long-term toxicity, reproductive toxicity, teratogenicity, immunotoxicity, or carcinogenicity. Based on existing data on α-cypermethrin, it can be concluded that this compound has not been found to be mutagenic in tests against Salmonella typhimurium, Escherichia coli, and Saccharomyces cerevisiae, nor in in vivo and in vitro tests on rat hepatocytes, and does not induce chromosomal aberrations or DNA single-strand damage. α-Cypermethrin is highly toxic to aquatic invertebrates, fish, and bees. The mechanism of action of type I and type II pyrethroid insecticides is to prolong the opening time of sodium ion channels during nerve cell excitation. They appear to bind to membrane lipids near sodium ion channels, thereby altering channel dynamics. This blocks the closure of sodium ion channels in nerves, thus prolonging the time it takes for the membrane potential to return to its resting state. Repetitive (sensory, motor) neuronal firing and sustained negative afterpotentials produce effects very similar to DDT, leading to nervous system overactivity, which can potentially cause paralysis and/or death. Other mechanisms of action of pyrethroids include antagonizing GABA-mediated inhibition, regulating nicotinic cholinergic transmission, enhancing norepinephrine release, and acting on calcium ions. They also inhibit calcium channels and Ca2+,Mg2+-ATPase. (T10, T18, L857)

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Toxicity Data
LC50 (Rat) > 400 mg/m3/4h
LD50: 250-300 mg/kg (oral, mouse) (L873)

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Interactions
/Pyrethroid/Detoxification…Important for fruit flies, but the addition of synergists (organophosphates or carbamates) may delay detoxification to ensure lethality. …/Pyrethroid/
Synergist ethers enhance/insectic activity/ by inhibiting hydrolytic enzymes responsible for pyrethroid metabolism in arthropods. When piperitin is used in combination with pyrethroids, the latter's insecticidal activity can be increased by 2-12 times. /Pyrethroids/
When 1000 ppm pyrethroids and 10000 ppm piperonyl butyl ether were added to the diet…/enlargement, marginalization, and cytoplasmic inclusions in rat hepatocytes/were noticeable within just 8 days, but…did not reach their maximum. These changes were dose-dependent and similar to the effects of DDT. The effects of the two drugs had an additive effect. /Pyrethroids/
This study investigated the effects of dissolved organic carbon in the form of Aldrich humic acid on the accumulation and acute toxicity of three synthetic pyrethroids—cypermethrin, deltamethrin, and cyhalothrin—in Daphnia magna under laboratory conditions. When the dissolved organic carbon concentrations were as low as 2.6 mg/L, 3.2 mg/L, and 3.1 mg/L, the bioaccumulation of deltamethrin, cypermethrin, and cyhalothrin were all significantly reduced. The acute toxicity of all three pyrethroids decreased with increasing dissolved organic carbon (COC) concentration; for example, the acute toxicity of cypermethrin decreased 17-fold at a COC concentration of 15.5 mg/L. At 2 and 24 hours of exposure, the percentage of cypermethrin and deltamethrin bound to COC increased with increasing COC concentration. At low COC concentrations (e.g., 1.7 mg/L), up to 40% of cypermethrin and 20% of deltamethrin were adsorbed by COC. At 24 hours of exposure, 76.4% and 80.8% of cypermethrin and deltamethrin, respectively, were bound to COC. The reverse partition coefficients of cypermethrin and deltamethrin varied with COC concentration, ranging from 1.0 to 4.8 to 5.6. Acute administration of 1R,cis,αS-cypermethrin, deltamethrin, cypermethrin, and permethrin dose-dependently reduced the pentylenetetrazol dose required to induce seizures in rats. The proconvulsant effect of cypermethrin was stereoselective, with the 1R,cis,αS-cypermethrin isomer exhibiting the strongest activity among the tested compounds, while the non-insecticide isomer 1S,cis,αR-cypermethrin showed no proconvulsant activity. Pretreatment of rats with the peripheral benzodiazepine binding site antagonist PK 11195 completely reversed the proconvulsant effects of deltamethrin and permethrin. Conversely, pretreatment with phenytoin sodium did not alter the pyrethroid-induced proconvulsant activity. These results indicate that the effect of pyrethroids on the pentylenetetrazol epileptogenic threshold is mediated through interactions with peripheral benzodiazepine binding sites. The detoxification effect of pyrethroids is important in fruit flies, but the addition of synergists—organophosphates or carbamates—may delay detoxification to ensure lethality. Pyrethroid synergists enhance the insecticidal activity of pyrethroids by inhibiting hydrolytic enzymes responsible for pyrethroid metabolism in arthropods. When piperitin is used in combination with pyrethroids, the latter's insecticidal activity can be increased 2-12 times. For more complete data on interactions of cypermethrins (9 in total), please visit the HSDB record page.

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Non-human toxicity values
Oral LD50 in rats: 79-400 mg/kg (soluble in corn oil, values depend on concentration), 474 mg/kg (technical concentration)
Dermal LD50 in rats: > 2000 mg/kg
Dermal LD50 in rabbits: > 2000 mg/kg
Oral LD50 in 8-day-old rats: 14.9 mg/kg
Oral LD50 in adult male rats: 250.0 mg/kg
Oral LD50 in rats: 4123 mg/kg
Dermal LD50 in rabbits: > 2460 mg/kg
For more complete non-human toxicity data for cypermethrin (10 in total), please visit the HSDB record page.

Therapeutic Uses
Pyrethroids and synergist are used for the topical treatment of head lice (lice infestation). The combination of pyrethroids and synergist is ineffective against scabies (scabies mite infestation). Although there are currently no well-controlled studies, many clinicians consider 1% lindane to be the first-line lice killer. However, some clinicians recommend the use of the combination of pyrethroids and synergist, especially in infants, children, and pregnant or lactating women… If used properly, 1-3 treatments usually achieve 100% efficacy… Oil-based (e.g., petroleum fraction) combinations… work fastest. When treating lice, apply an appropriate amount of gel, shampoo, or solution to the affected area and surrounding hair. After 10 minutes, thoroughly wash the hair. Repeat the treatment after 7-10 days to kill newly hatched lice. /Pyrethroids/
Therapeutic Category (Veterinary): External Parasite Killer

415.074

67375-30-8

2912

Viscous yellowish brown semisolid mass.
Colorless crystals
Viscous semi-solid
Colorless crystals - pure isomers

1.3±0.1 g/cm3

511.3±50.0 °C at 760 mmHg

78-81ºC

263.0±30.1 °C

0.0±1.3 mmHg at 25°C

1.622

6.27

0

4

7

28

643

0

KAATUXNTWXVJKI-UHFFFAOYSA-N

InChI=1S/C22H19Cl2NO3/c1-22(2)17(12-19(23)24)20(22)21(26)28-18(13-25)14-7-6-10-16(11-14)27-15-8-4-3-5-9-15/h3-12,17-18,20H,1-2H3

[cyano-(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.)