Absorption, Distribution and Excretion
Following oral administration, pyrethroids are absorbed via the gastrointestinal tract. Studies in male rats with oral administration of 3 mg/kg pyrethroids showed almost complete absorption and metabolism within 100 hours. Pyrethroids were not detected in urine, but significant amounts of metabolites were present. Small amounts of maternal pyrethroids, also accompanied by metabolites, were detected in feces. Topical application of pyrethroids can be absorbed through intact skin. When animals were exposed to aerosols containing pyrethroids and synergist ethers, little or no systemic absorption of the mixture was observed. /Pyrethroids/ It is currently unclear whether pyrethroids or their metabolites are stored in the body or excreted in breast milk… Following a single oral administration of pyrethroid II in rats, 53% of the administered dose was excreted as carbon dioxide, and 7% appeared in the urine. After administration of an equivalent dose of pyrethroid I, 0.3% was excreted as carbon dioxide, and 46% was excreted in the urine.

---

Metabolism/Metabolites
Pyrethroids are widely metabolized, with only 10% of the parent compound remaining in feces and urine. Six metabolites have been identified, and two main metabolic pathways have been proposed: the first involves the oxidation of double bonds and/or methyl groups; the second involves the hydrolysis of ester bonds. Pyrethroid I is primarily metabolized via oxidation, while pyrethroid II is metabolized via a combination of hydrolysis and oxidation.
...Within 48 hours after oral administration of 14C-labeled pyrethroid II to rats, 53% of the 14C was recovered as exhaled carbon dioxide... The 14C recovered from urine... was 7%... Some orally administered substances are excreted in feces, at least partially in metabolic form. Three compounds have been isolated from urine and identified by NMR and mass spectrometry. All three compounds are produced by pyrethroids I and II. All three compounds are the result of partial oxidation of acidic and alcoholic components, while the main molecular structure remains unchanged. After oral administration of radiolabeled pyrethroid I or II to rats, multiple metabolites were produced in their urine. Each compound contained a trans-2-carboxypropyl-1-enyl side chain, resulting from the oxidation of the isobutylene group of chrysanthemin or the hydrolysis of the methoxycarbonyl group of pyrethroid. Furthermore, the cis-2',4'-pentadienyl side chain of pyrethroid I and pyrethroid II was oxidized at the pent-2,4-dienyl group to generate cis-4',5'-dihydroxypent-2'-enyl, the 4' conjugate of the diol, or trans-2',5'-dihydroxypent-3'-enyl. The 2-methylpropenyl group of (S)-bioallethrin (A) and the pentadienyl group of pyrethrin II are selectively oxidized in dichloromethane by m-chloroperoxybenzoic acid to generate 7,8-epoxide (1) from A and a mixture of 8',9'- and 10',11'-epoxides (7 and 8) from pyrethrin II. These epoxides are hydrated in acidic aqueous solution to generate the corresponding diols and other hydroxyl derivatives, which are generated due to ring-opening of the cyclopropyl ring or migration of adjacent double bonds. The epoxide and hydroxyl derivatives can be identified by two-dimensional nuclear magnetic resonance (NMR). The hydration reaction of epoxide 1 with mouse liver enzymes is undetectable, but epoxides 7 and 8 are rapidly hydrated without double bond migration. High-performance liquid chromatography (HPLC) analysis of the microsomal metabolites of pyrethrin I and II showed that 10',11'-diol is the major metabolite and 8',9'-diol is the minor metabolite. For more complete metabolite/metabolite data on pyrethroid II (12 metabolites in total), please visit the HSDB record page.

Interactions
Synergists enhance the insecticidal activity of pyrethroids by inhibiting hydrolytic enzymes responsible for pyrethroid metabolism in arthropods. When synergists are used in combination with pyrethroids, the latter's insecticidal activity can be increased 2-12 times. Adding 1000 ppm pyrethroids and 10000 ppm synergists to feed resulted in noticeable enlargement, marginalization, and cytoplasmic inclusions in rat hepatocytes within just 8 days, though these changes did not reach their maximum. These changes were dose-proportional and similar to the effects of DDT. The effects of the two synergists have an additive effect. There is currently no evidence that synergists increase the toxicity of pyrethroids to mammals. /Pyrethroids/ Antioxidants used to protect pyrethroid insecticidal residues include trace amounts of catechol, pyrogallol, and hydroquinone; 1-benzano-2-naphthol is used to protect them from sunlight.
/Experimental Animals: Developmental or Reproductive Toxicity/...Extracts containing pyrethroids and synergistic ethers were applied to the chorioallantoic membrane of chicken embryos, resulting in testicular damage and gonadal cell loss in surviving chicken embryos. /Pyrethrum Extract/

---

Non-human Toxicity Values
LD50 Male Rat Oral > 600 mg/kg
LD50 Mouse Intraperitoneal < 240 mg/kg
LD50 Female Cat Intravenous 1 mg/kg
LD50 Rat Oral 1.2 g/kg
For more complete non-human toxicity data on pyrethroid II (8 in total), please visit the HSDB record page.

[1].Residual determination of pyrethrins in Lycium barbarum (goji) by GC-MS/MS and a dietary risk assessment of Chinese goji consumption. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2020 Mar;37(3):478-487.

Pyrethroid II is a member of the pyrethroid family, and its function is related to that of pyrethroid I.

---

Mechanism of Action
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 were observed in neuromuscular specimens of insects and crustaceans poisoned with pyrethroids. The primary target of pyrethroids appears to be the ganglia of the insect central nervous system, although some pyrethroid poisoning effects were also observed in detached legs. /Pyrethroids/
From an electrophysiological perspective, pyrethroids cause repetitive discharges and conduction block. Pyrethroid Compounds
The primary site of action for pyrethroid compounds is the sodium ion channels of nerve cells. Using various methods, including voltage-clamp and patch-clamp techniques, it has been confirmed that pyrethroids can slow down the closure of sodium ion channel gates after the initial influx of sodium ions during the depolarization phase of the action potential, thereby prolonging the sodium ion tail current. After absorption by the chitinous exoskeleton of arthropods, pyrethroids stimulate the nervous system. Their mechanism of action appears to be through competitive interference with the cation conductivity in the lipid layer of nerve cells, thereby blocking nerve impulse transmission, ultimately leading to paralysis and death. This study investigated the interaction between natural pyrethroids and nine pyrethroid compounds with the nicotinic acetylcholine (ACh) receptor/channel complex on the electron organ membrane of the electric ray. None of the compounds reduced the binding of 3H-ACh to the receptor site, but in the presence of carbamoylcholine, all compounds inhibited the binding of 3H-labeled perhydrohistidine toxin to the channel site. Allethrin inhibits binding non-competitively, while 3H-labeled imipramine inhibits binding competitively, indicating that allethrin binds to the channel site on the receptor where imipramine binds. Based on their mechanism of action, pyrethroids are divided into two classes: Class A (including allethrin) has a stronger ability to inhibit 3H-H12-HTX binding and a faster onset of action; Class B (including permethrin) is less potent, and its potency increases slowly over time. The high affinity of several pyrethroids for nicotinic acetylcholine receptors suggests that, in addition to their known effects on axonal channels, pyrethroids may also have synaptic action sites. /Pyrethroids and Pyrethroids/

---

Therapeutic Use
…This insecticide was once considered harmless, so much so that ointments containing 0.75% pyrethrin were recommended for the treatment of scabies, but this use resulted in only a few cases of dermatitis, some of which remain questionable in relation to treatment. Pyrethroids are widely used to control human lice. Head lice can be treated with 0.3% pyrethroid plus 3% synergist. Drug Warnings: Commercially available formulations are irritating to the eyes and mucous membranes and should not be used to treat pubic lice on the eyelashes. People allergic to ragweed may have cross-sensitivity to unrefined pyrethroids but not to refined pyrethroids; however, manufacturers of pyrethroid combination formulations warn that these products should not be used by people with ragweed allergies. Local irritation may occur, including erythema, itching, urticaria, edema, eczema, and mild corneal erosion and stromal edema… Avoid contact with the face, eyes, mucous membranes, and urethral opening. …Pyrethroid and synergist combination formulations should not be applied to acutely inflamed skin or broken, oozing skin. …This medication should not be used more than twice in 24 hours.

C22H28O5

372.45

372.193

121-29-9

5281555

Light yellow to yellow liquid

1.1±0.1 g/cm3

473.7±45.0 °C at 760 mmHg

203.8±28.8 °C

0.0±1.2 mmHg at 25°C

1.528

4.43

0

5

9

27

751

3

CC1=C(C(=O)C[C@@H]1OC(=O)[C@@H]2[C@H](C2(C)C)/C=C(\C)/C(=O)OC)C/C=C\C=C

VJFUPGQZSXIULQ-XIGJTORUSA-N

InChI=1S/C22H28O5/c1-7-8-9-10-15-14(3)18(12-17(15)23)27-21(25)19-16(22(19,4)5)11-13(2)20(24)26-6/h7-9,11,16,18-19H,1,10,12H2,2-6H3/b9-8-,13-11+/t16-,18+,19+/m1/s1

[(1S)-2-methyl-4-oxo-3-[(2Z)-penta-2,4-dienyl]cyclopent-2-en-1-yl] (1R,3R)-3-[(E)-3-methoxy-2-methyl-3-oxoprop-1-enyl]-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)

DMSO :~100 mg/mL (~268.49 mM; with sonication)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.71 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (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 and add it to 400 μL PEG300 and mix well. Then add 50 μL Tween-80 to the above system and mix well. Then continue to add 450 μL of physiological saline to make up to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

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