Absorption, Distribution and Excretion
WHEN RADIOACTIVE PYRETHROID IS ADMIN ORALLY TO MAMMALS, IT IS ABSORBED FROM INTESTINAL TRACT OF THE ANIMALS & DISTRIBUTED IN EVERY TISSUE EXAMINED. EXCRETION OF RADIOACTIVITY IN RATS ADMIN TRANS-ISOMER: DOSAGE: 500 MG/KG; INTERVAL 20 DAYS; URINE 36%; FECES 64%; TOTAL 100%. /PYRETHROIDS/
Pyrethrins are absorbed through intact skin when applied topically. When animals were exposed to aerosols of pyrethrins with piperonyl butoxide being released into the air, little or none of the combination was systemically absorbed. /Pyrethrins/
Although limited absorption may account for the low toxicity of some pyrethroids, rapid biodegradation by mammalian liver enzymes (ester hydrolysis and oxidation) is probably the major factor responsible. Most pyrethroid metabolites are promptly excreted, at least in part, by the kidney. /Pyrethroids/
There were no major /metabolic/ differences between sexes, between low and high dose groups, nor between single-dose groups and repeated dose groups. The majority of radioactivity was eliminated within 3 days. Urinary elimination ranged from approximately 25 - 50% and fecal elimination ranged from 50 - 70%. There was no bioaccumulation of residue in tissues. ... /d-trans-Allethrin/
When allethrin labelled with (14)C in the acid moiety or with (3)H in the alcohol moiety was administered orally to male Sprague Dawley rats at levels ranging from 1 to 5 mg/kg body weight, the radiocarbon and tritium from the acid- and alcohol-labellings were eliminated in the urine (30% and 20.7%, respectively) and feces (29% and 27%, respectively) in 48 hr. ... Most of the metabolites excreted in the urine were ester-form metabolites together with two hydrolyzed products, chrysanthemum dicarboxylic acid (CDCA) and allethrolone. ...

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Metabolism / Metabolites
AFTER ADMINISTRATION OF LABELED ALLETHRIN TO MALE RATS, THE MAJOR METABOLITES FOUND WERE ALCOHOL-ACIDS. FROM NMR AND MASS SPECTRA A THIRD METABOLITE WAS IDENTIFIED AS ALLETHRIN WITH ONE CYCLOPROPANE METHYL HYDROXYLATED AND OXIDATION OF THE TRANSMETHYL TO A CARBOXYL GROUP. ...
/IN STUDYING THE METABOLISM OF ALLETHRIN IN HOUSEFLIES, IT WAS FOUND THAT IN/ ALLETHRIN LABELED IN THE KETOCYCLOPENTENYL PORTION OF THE MOLECULE, A METABOLITE THAT BEHAVED AS KETOCYCLOPENTENOL WAS ISOLATED BY PAPER CHROMATOGRAPHY. ... INVESTIGATORS USING ALLETHRIN LABELED IN CHRYSANTHEMUMIC ACID PORTION OF MOLECULE WERE ABLE TO DETECT ONLY TRACES OF ACID IN HOUSEFLY HOMOGENATES OR EXCRETA. ... ONLY TRACES OF UNCHANGED ALLETHRIN WERE RECOVERABLE AND THE BULK OF THE RECOVERED MATERIAL MUST BE A DERIVATIVE OF THE INTACT ESTER OR OF THE ACID.
Allethrin is oxidized not only at the chrysanthemate isobutenyl moiety to the corresponding primary alcohol but also at the allyl group to 1'-hydroxyprop-2'-enyl and 2',3'-dihydroxy-propyl derivatives, or at a methyl group on the cyclopropyl moiety to a hydroxy derivative. Allethrin is also converted to chrysanthemum dicarboxylic acid and allethrolone.
When allethrin was applied topically to houseflies, chromatography indicated the presence of allethrone and chrysanthemic acid in addition to allethrin and three unidentified compounds.
For more Metabolism/Metabolites (Complete) data for ALLETHRINS (10 total), please visit the HSDB record page.
Upon absorption of allethrine , biotransformation takes place through hydrolysis of the

central ester bond, oxidative attacks at several sites, and conjugation reactions to produce a complex array of primary and secondary water-soluble metabolites that undergo urinary and biliary excretion. Allethrin is oxidized not only at the chrysanthemate isobutenyl moiety to the corresponding primary alcohol but also at the allyl group to 1'-hydroxyprop-2'-enyl and 2',3'-dihydroxy-propyl derivatives, or at a methyl group on the cyclopropyl moiety to a hydroxy derivative. It is widely accepted that metabolism results in the formation of compounds that have little or no demonstrable toxicity, although the formation of reactive or toxic intermediates cannot be ruled out, and it appears that cleavage of the ester bond results in substantial detoxification. Allethrin is also converted to chrysanthemum dicarboxylic acid and allethrolone. Allethrin leaves the body quickly, mainly in the urine, but also in feces and breath. (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 appears as a clear amber-colored viscous liquid. Insoluble and denser than water. Toxic by ingestion, inhalation, and skin absorption. A synthetic household insecticide that kills flies, mosquitoes, garden insects, etc.
D-trans-allethrin is a clear to amber viscous liquid. A synthetic insecticide structurally similar to pyrethrin.
Allethrin is a cyclopropanecarboxylate ester. It has a role as a pyrethroid ester insecticide. It is functionally related to a chrysanthemic acid.
Allethrin is a pyrethroid (type I) insecticide. A pyrethroid is a synthetic chemical compound similar to the natural chemical pyrethrins produced by the flowers of pyrethrums (Chrysanthemum cinerariaefolium and C. coccineum). Pyrethroids are common in commercial products such as household insecticides and insect repellents. In the concentrations used in such products, they are generally harmless to human beings but can harm sensitive individuals. They are usually broken apart by sunlight and the atmosphere in one or two days, and do not significantly affect groundwater quality except for being toxic to fish. (L811)
Synthetic analogs of the naturally occurring insecticides cinerin, jasmolin, and pyrethrin. (From Merck Index, 11th ed)
See also: Bioallethrin (annotation moved to); S-Bioallethrin (annotation moved to).

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Mechanism of Action
Mode of Action: The allethrins are a type I pyrethroid (i.e., lacking a cyano group at the alpha carbon position of the alcohol moiety). The allethrins are axonic poisons that block the closing of the sodium gates in the nerves, and, thus, prolong the return of the membrane potential to its resting state leading to hyperactivity of the nervous system which can result in paralysis and/or death.
The mechanisms by which pyrethroids alone are toxic are complex and become more complicated when they are co-formulated with either piperonyl butoxide or an organophosphorus insecticide, or both, as these compounds inhibit pyrethroid metabolism. The main effects of pyrethroids are on sodium and chloride channels. Pyrethroids modify the gating characteristics of voltage-sensitive sodium channels to delay their closure. A protracted sodium influx (referred to as a sodium 'tail current') ensues which, if it is sufficiently large and/or long, lowers the action potential threshold and causes repetitive firing; this may be the mechanism causing paraesthesiae. At high pyrethroid concentrations, the sodium tail current may be sufficiently great to prevent further action potential generation and 'conduction block' ensues. Only low pyrethroid concentrations are necessary to modify sensory neurone function.
The interactions of natural pyrethrins and 9 pyrethroids with the nicotinic acetylcholine (ACh) receptor/channel complex of Torpedo electronic organ membranes were studied. None reduced (3)H-ACh binding to the receptor sites, but all inhibited (3)H-labeled perhydrohistrionicotoxin binding to the channel sites in presence of carbamylcholine. Allethrin inhibited binding noncompetitively, but (3)H-labeled imipramine binding competitively, suggesting that allethrin binds to the receptor's channel sites that bind imipramine. The pyrethroids were divided into 2 types according to their action: type A, which included allethrin, was more potent in inhibiting (3)H-H12-HTX binding and acted more rapidly. Type B, which included permethrin, was less potent and their potency increased slowly with time. The high affinities that several pyrethroids have for this nicotinic ACh receptor suggest that pyrethroids may have a synaptic site of action in addition to their well known effects on the axonal channels.
Phosphoinositide breakdown in guinea pig cerebral cortical synaptoneurosomes induced by the Type I pyrethroids allethrin, resmethrin, and permethrin and the Type II pyrethroid deltamethrin and fenvalerate were investigated with various receptor agonists as well as sodium channel blockers and agents. Phosphoinositide breakdown was determined from inositol-phosphate formation by tritiated inositol labeled synaptoneurosomes. All five pyrethroids dose dependently induced phosphoinositide breakdown. Type II pyrethroids exhibited higher potency and deltamethrin was more efficacious than the Type I pyrethroids. Five micromolar tetrodotoxin, a blocker of voltage dependent sodium channels, partially inhibited deltamethrin (85%) and fenvalerate (60%) responses but not allethrin or resmethrin. Fenvalerate induced stimulation of phosphoinositide breakdown was additive with stimulation elicited by the receptor agonists carbamylcholine (1 mM) and norepinephrine (1000 uM) but less than additive with the sodium channel agents batrachotoxin, pumiliotoxin-B, and scorpion venom. Allethrin (100 uM) was less than additive with receptor agonists or sodium channel agents and actually significantly inhibited response to scorpion venom. Effects for 100 uM allethrin with either fenvalerate or deltamethrin were not different from allethrin alone. Ten micromolar allethrin slightly decreased response to 10 to 100 uM deltamethrin. The local anesthetic dibucaine, a sodium channel activation inhibitor, completely blocked deltamethrin induced phosphoinositide breakdown but was much less effective in inhibiting allethrin response. It appears likely that Type-I pyrethroids induce phosphoinositide breakdown through a mechanism other than sodium channel activation while Type-II pyrethroids act in a manner analogous to other sodium channel agents.
For more Mechanism of Action (Complete) data for ALLETHRINS (13 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.)