Absorption, Distribution and Excretion
When radioactive pyrethroids are administered orally to mammals, they are absorbed from 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 pyrethroid aerosols containing synergistic ethers, little or no systemic absorption of the mixture is observed. Pyrethroids
While the low toxicity of some pyrethroids may be related to their limited absorption, rapid biodegradation by mammalian liver enzymes (ester hydrolysis and oxidation) is likely the primary cause. Most pyrethroid metabolites are rapidly excreted, at least partially, by the kidneys.
No significant differences were observed in metabolism between sexes, low-dose and high-dose groups, or between single-dose and repeated-dose groups. Most radioactive material is cleared within 3 days. The urinary excretion rate was approximately 25% to 50%, and the fecal excretion rate was approximately 50% to 70%. No bioaccumulation of residues was observed in tissues. …/d-trans-allethrin/
When male Sprague Dawley rats were orally administered allethrin labeled with (14)C (acid moiety) or (3)H (alcohol moiety), radiocarbon and tritium from the acid and alcohol labels were excreted in urine (30% and 20.7%, respectively) and feces (29% and 27%, respectively) within 48 hours. …The metabolites excreted in urine were mostly ester metabolites, as well as two hydrolysis products: chrysanthemum dicarboxylic acid (CDCA) and acrylone. …

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Metabolism/Metabolites
The major metabolite found after administration of labeled allethrin to male rats was an alcoholic acid. The third metabolite was identified as allethrin by nuclear magnetic resonance and mass spectrometry analysis. One of its cyclopropane methyl groups was hydroxylated, and the trans methyl group was oxidized to a carboxyl group. ...
In studying the metabolism of allethrin in flies, a metabolite exhibiting the form of ketocepenol was isolated by paper chromatography from allethrin labeled with the ketocepenyl moiety. Researchers used allethrin labeled with chrysanthemic acid, and only trace amounts of chrysanthemic acid were detected in housefly homogenates or excrement. Only trace amounts of unmodified allethrin could be recovered; most of the recovered substance was necessarily an intact ester or a derivative of chrysanthemic acid. Allethrin is not only oxidized to the corresponding primary alcohol at the isobutylenyl moiety of chrysanthemic acid, but also oxidized at the allyl group to 1'-hydroxypropyl-2'-enyl and 2',3'-dihydroxypropyl derivatives, or oxidized at the methyl group of the cyclopropyl moiety to a hydroxyl derivative. Allethrin can also be converted into chrysanthemic dicarboxylic acid and allyl ketone. When allethrin was applied topically to houseflies, chromatographic analysis revealed the presence of allethrin and three unidentified compounds, as well as allethrin and chrysanthemic acid. For more complete metabolite/metabolite data on allethrin compounds (10 in total), please visit the HSDB record page. After absorption, allethrin undergoes biotransformation via: hydrolysis of the central ester bond, oxidative attack at multiple sites, and conjugation reactions, generating a complex series of water-soluble primary and secondary metabolites, which are ultimately excreted in urine and bile. Allethrin is oxidized not only at the isobutylenyl moiety of chrysanthemic acid to the corresponding primary alcohol, but also at the allyl moiety to 1'-hydroxypropyl-2'-enyl and 2',3'-dihydroxypropyl derivatives, or at the methyl group of the cyclopropyl moiety to a hydroxyl derivative. Its metabolites are generally considered to have low or negligible toxicity, although the possibility of generating active or toxic intermediates cannot be ruled out, and ester bond cleavage appears to significantly detoxify. Allethrin can also be converted into chrysanthemum dicarboxylic acid and acrylone. Allethrin is rapidly excreted from the body, primarily through urine, but also through feces and respiration. (L857, A558)

[1]. Differential state-dependent modification of inactivation-deficient Nav1.6 sodium channels by the pyrethroid insecticides S-bioallethrin, tefluthrin and deltamethrin. Neurotoxicology. 2012;33(3):384-390.

Allethrin is a transparent, amber-colored viscous liquid, insoluble in water, and denser than water. It can cause poisoning through ingestion, inhalation, and skin absorption. It is a synthetic household insecticide that kills flies, mosquitoes, garden insects, etc. D-trans-allethrin is a transparent to amber-colored viscous liquid, a synthetic insecticide with a structure similar to pyrethroids. Allethrin is a cyclopropane carboxylic acid ester, belonging to the pyrethroid insecticide class, and its function is similar to chrysanthemum acid. Allethrin is a type I pyrethroid insecticide. Pyrethroids are synthetic compounds whose structure is similar to that of pyrethroids, the natural chemicals produced by the flowers of plants in the genus Pyrethrum (such as Grey's Chrysanthemum and Red Chrysanthemum). 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 individuals. They are typically decomposed by sunlight and atmosphere within one or two days, and have no significant impact on groundwater quality except for their toxicity to fish. (L811)
Synthetic analogs of natural insecticides pyrethroids, jasmine, and pyrethroids. (From Merck Index, 11th edition)
See also: bio-allethrin (note moved to); S-bio-allethrin (note moved to).

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Mechanism of Action
Method of action: Allethrin belongs to type I pyrethroids (i.e., lacking a cyano group at the α-carbon position of the alcohol moiety). Allethrins are axonotoxins that block the closure of sodium ion channels in nerves, thereby prolonging the time it takes for the membrane potential to return to the resting state, leading to nervous system hyperactivity, which may ultimately cause paralysis and/or death. The mechanisms by which pyrethroids produce toxicity on their own are complex, and become even more complicated when co-formulated with synergistic ethers or organophosphate insecticides (or both), as these compounds inhibit pyrethroid metabolism. The primary targets of pyrethroids are sodium and chloride channels. Pyrethroids alter the gating properties of voltage-sensitive sodium channels, delaying their closure. This generates a sustained sodium influx (called a sodium "tail current"), which, if large enough and/or prolonged enough, lowers the action potential threshold, leading to repetitive discharges; this may be the mechanism causing sensory abnormalities. In high-concentration pyrethroid solutions, the sodium tail current can be large enough to prevent further action potential generation, resulting in "conduction block." Even low concentrations of pyrethroids can alter the function of sensory neurons. This study investigated the interactions of natural pyrethroids and nine other pyrethroids with nicotinic acetylcholine (ACh) receptor/channel complexes 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 perhydrohistamine toxin to the channel site. Allethrin inhibited binding non-competitively, while 3H-labeled imipramine inhibited 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 (3)H-H12-HTX binding and a faster onset of action; Class B (including permethrin) has a weaker inhibitory ability, and its efficacy increases slowly over time. Many pyrethroids have high affinity for nicotine acetylcholine receptors, suggesting that pyrethroids may have synaptic action sites in addition to their known effects on axonal channels. This study investigated the induction of phosphatidylinositol degradation in the synaptosomes of the cerebral cortex in guinea pigs by various class I pyrethroids (allethrin, permethrin, and cypermethrin) and class II pyrethroids (deltamethrin and cypermethrin). The degradation of phosphatidylinositol was determined by measuring the production of inositol phosphate in tritium-labeled inositol-labeled synaptosomes. All five pyrethroids induced phosphatidylinositol degradation in a dose-dependent manner. Class II pyrethroids were more potent, with deltamethrin being more potent than class I pyrethroids. 5 μM tetrodotoxin (a voltage-dependent sodium channel blocker) partially inhibited the response of deltamethrin (85%) and cypermethrin (60%), but had no effect on allethrin and permethrin. Cypermethrin-induced phosphatidylinositol degradation exhibits an additive effect with stimulation from the receptor agonists carbamoylcholine (1 mM) and norepinephrine (1000 μM), but not with stimulation from sodium channel blockers such as dart poison, pumilatoxin-B, and scorpion venom. The interaction of 100 μM allethrin with receptor agonists or sodium channel blockers is less than additive and significantly inhibits the response to scorpion venom. The effect of 100 μM allethrin in combination with cypermethrin or deltamethrin is not significantly different from that of allethrin alone. 10 μM allethrin slightly reduces the response to 10–100 μM deltamethrin. The local anesthetic debucaine, a sodium channel activation inhibitor, completely blocks deltamethrin-induced phosphatidylinositol degradation, but its inhibitory effect on the allethrin response is much weaker. Type I pyrethroid insecticides may induce phosphatidylinositol degradation through mechanisms other than sodium channel activation, while Type II pyrethroid insecticides act in a manner similar to other sodium channel blockers. For more complete data on the mechanisms of action of allethrin insecticides (13 in total), please visit the HSDB record page.

C19H26O3

302.41

302.188

28434-00-6

11442

Light yellow to yellow liquid

1.05 g/cm3

386.8ºC at 760 mmHg

49.5ºC

166ºC

3.46E-06mmHg at 25°C

1.505 (25ºC)

4.002

0

3

6

22

574

0

[C@@H]1([C@@H](C1(C)C)C(O[C@@H]2C(=C(CC=C)C(C2)=O)C)=O)C=C(C)C

ZCVAOQKBXKSDMS-UHFFFAOYSA-N

InChI=1S/C19H26O3/c1-7-8-13-12(4)16(10-15(13)20)22-18(21)17-14(9-11(2)3)19(17,5)6/h7,9,14,16-17H,1,8,10H2,2-6H3

(2-methyl-4-oxo-3-prop-2-enylcyclopent-2-en-1-yl) 2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropane-1-carboxylate

AI-3-29024; AI 3-29024; S-Bioallethrin

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 (~330.68 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.27 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: 2.5 mg/mL (8.27 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
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 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (8.27 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.)