Neurotoxicity is observed at 15 mg/kg/day of esfenvalerate (0.1, 1, 7.5, or 15 mg/kg/day; gavage; from GD 13 to 19) [1].

Absorption, Distribution and Excretion
Pregnant rats on day 13 of gestation were administered (14)C-labeled ivermectate or (14)C-labeled fenvalerate (acid fraction) orally once or five times daily at doses of 2.5 and 10 mg/kg/day, respectively. Results showed that (14)C levels were generally higher in maternal blood and placenta compared to fetal and amniotic fluid. Neither compound nor its metabolites readily transferred from maternal blood to the fetus, with less than 0.07% of the dose transferred. There were no significant differences between the two labeled formulations in fetal (14)C levels and the transfer rate ((14)C tissue level/(14)C maternal blood level). The major 14C compounds in fetal, maternal blood, and placenta were the maternal compound CPIA (2-(4-chlorophenyl)isovalerate) and its hydroxylated derivatives. Aside from the detection of trace amounts of CPIA cholesterol ester (cholesterol(2R)-2-(4-chlorophenyl)isovalerate) in maternal blood and placenta, the metabolic pathways of the two compounds remain inconclusive. CPIA cholesterol ester does not appear to transfer from maternal blood to the fetus. Overall, fenvalerate and fenvalerate appear to behave similarly in terms of placental transport. Yttrium-rich pyridine insecticides are an isomer-enriched form of fenvalerate, with the ratio of the active diastereomers SS and RR (labeled Y) to the less active diastereomers RS and SR (labeled X) being approximately 85:15. The ratio of Y to X in fenvalerate is 45:55. Following a single oral administration of yttrium-rich insecticides (8.4 mg/kg) to male and female Sprague-Dawley rats, over 90% of the radioactivity from the acidic moiety (chlorophenyl-(14)C) and the alcoholic moiety (phenoxyphenyl-(14)C) was eliminated within 24 hours. The two different fenvalerate formulations showed no significant difference in elimination rate or metabolite distribution. Ester bond cleavage was the primary metabolic pathway. The acid and alcohol portions of the parent molecule underwent hydroxylation, oxidation, and conjugation reactions. These metabolic reactions were independent of the isomer composition of the test material. Tissue residue data showed that (14)C residues were not retained in various organs… /Pyridine insecticides (Y-rich)/
After a single oral administration of four chiral isomers (2.5 mg/kg body weight) of (14)C-chlorophenyl cypermethrin to Sprague-Dawley rats and ddY mice, the (2R, αS) isomer showed relatively high residue levels in the analyzed tissues (excluding adipose tissue) of both rats and mice, particularly in the adrenal glands, compared to the other three isomers. Similarly, when mice were fed a diet containing 500 mg/kg of the (2S, αS), (2R, αS), or (2R, αR) isomer for two consecutive weeks, the concentration of this isomer in tissues was higher than that of the other isomers. Compared to other isomers, the (2R, αS) isomer exhibited higher radioactive residues after administration. This is because the (2R, αS) isomer preferentially generates a lipophilic metabolite, which is present in all tested tissues and is not readily excreted. The content of this lipophilic metabolite varied across different tissues, with higher levels observed in the adrenal glands, liver, and mesenteric lymph nodes. This metabolite was identified as cholesterol (2R)-2-(4-chlorophenyl)isovalerate. The same metabolite was also detected in rat tissues… /Cypermethrin Isomers/
Two 3-month-old lambs were slaughtered after being fed a diet containing 45 mg/kg cypermethrin for 10 days. The concentrations of cypermethrin in the kidneys, liver, leg muscles, and kidney fat were determined… Among the analyzed tissues, the highest cypermethrin content was found in fat (3.6–4.4 mg/kg dry weight), while other tissues contained less than 0.3 mg/kg. Cypermethrin exhibits two peaks in gas chromatography, each containing a pair of enantiomers. In all cases, the peak area ratio (peak 1 (RS,SR)/peak 2 (SS,RR)) of cypermethrin in the diet and that recovered from fortified control fat was 1.08. In contrast, the peak area ratio of cypermethrin isolated from lamb fat was 0.76–0.78. Therefore, one or both of the first two enantiomers eluted appear to be metabolized more rapidly than the others. /Cypermethrin Isomers/
For more complete data on the absorption, distribution, and excretion of ESFENVALERATE (9 in total), please visit the HSDB record page.

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Metabolism/Metabolites
The metabolism of racemic cypermethrin and its (2S, αS) isomers was investigated in cabbage plants grown under laboratory conditions. These plants were treated with two compound formulations labeled (14)C-chlorophenyl and phenyl-(14)C-benzyl (20 μg per leaf). Both compounds disappeared from the treated leaves with a half-life of approximately 12–14 days. Significant ester bond cleavage occurred, along with hydroxylation at the 2 or 4 position of the phenoxy ring, and hydrolysis of the nitrile group to generate amide and carboxyl groups. Most of the resulting carboxylic acids and phenolic compounds existed as glycoside conjugates. …In the laboratory, we studied the absorption and metabolism of 2-(4-chlorophenyl)isoglutaric acid (CPIA) using leaves from common bean, cabbage, cotton, cucumber, and tomato plants. The results showed that the acid…is mainly converted to glucose or 6-O-malonyl glucose ester in common bean, cabbage, and cucumber; to glucosyl xylose ester, sophorose ester, and gentiobiose ester in cotton; and to two different isomers of triglucose ester in tomato. One of the acetyl-derived glucoside conjugates is identical to the standard decaacetyl(1-6)-triglucoester derivative… Pyridine insecticides (enriched with Y) are enriched isomers of cypermethrin, with the ratio of the active diastereomers SS and RR (labeled Y) to the less active diastereomers RS and SR (labeled X) being approximately 85:15. The ratio of Y to X in cypermethrin is 45:55. After a single oral administration of the Y-enriched insecticide (8.4 mg/kg) to male and female Sprague-Dawley rats… there were no significant differences in metabolite distribution between chlorophenyl-(14)C- and phenoxyphenyl-(14)C-cypermethrin formulations. Ester bond cleavage was the dominant metabolic pathway. The acid and alcohol portions of the parent molecule underwent hydroxylation, oxidation, and conjugation reactions. These metabolic reactions were independent of the isomer composition of the test material. Tissue residue data showed that (14)C residues were not retained in various organs… /Pyridine insecticides (rich in Y)/
In mice, cypermethrin is metabolized similarly to rats, but the following significant species differences were observed…(a) The taurine conjugate of phenoxybenzoic acid (PBacid) was found in mice but not in rats; (b) The content of 4'-OH-PBacid sulfate was higher in rats than in mice; (c) Mice excreted more thiocyanate than rats. No significant sex differences were observed in rats and mice. The metabolism of flufenoxuron stereoisomers ((2S, αRS) and (2S, αS)) was significantly similar to that of racemic flufenoxuron.
In an in vitro study, researchers investigated the metabolism of four chiral isomers of flufenoxuron using various tissue homogenates from mice, rats, dogs, and monkeys. The results showed that only the (2R, αS) isomer produced cholesterol-(2R)-2-(4-chlorophenyl)isovalerate (CPIA-cholesterol ester) as the major metabolite. The rate of CPIA-cholesterol ester formation in mouse tissues was higher than in other animals. Among the mouse tissues tested, the kidneys, brain, and spleen showed the strongest ability to produce this ester, with the relevant enzymatic activity primarily localized in the microsomal fraction. Mouse renal microsomal carboxylesterase hydrolyzed only the (2R, αS) isomer of cyanovalerate to generate CPIA, and in the presence of cholesterol-containing artificial liposomes, generated the corresponding cholesterol ester. CPIA-cholesterol ester formation appears to be due to the stereoselectivity of the CPIA-carboxylesterase complex (only (2R, αS)), which subsequently reacts with cholesterol to generate CPIA-cholesterol ester… Mouse kidney, spleen, and brain tissues hydrolyzed only the (2R, αS) isomer. The liver hydrolyzes the (2R, αS) and (2R, αR) isomers to a greater extent than the (2S, αR) and (2S, αS) isomers, while plasma hydrolyzes the (2S, αR) and (2R, αR) isomers faster than the (2S, αS) and (2R, αS) isomers. The stereoselectivity of mouse liver microsomes for hydrolysis of these four isomers is consistent with that in vivo. Of these four isomers, only the (2R, αS) isomer can be converted to cholesterol-(2R)-2-(4-chlorophenyl)isovalerate (CPIA-cholesterol ester) by brain, kidney, spleen, or liver microsomes, but not by plasma. The rate of CPIA-cholesterol ester formation in the liver is lower than in other tissues. The optimal pH for ester formation (7.4–9.0) is almost identical to the optimal pH for the hydrolysis of the (2R, αS) isomer to CPIA in mouse kidney microsomes. /Fenvalerate isomers/
For more complete metabolite/metabolite data on fenvalerate (8 in total), please visit the HSDB record page.

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Biological half-life
One male and one female Sprague-Dawley rat and four male and four female ddY mice were given a single oral dose of 7 mg/kg body weight of ((14)C-carbonyl)-, ((14)C-benzyl)-, or ((14)C-cyano)-fenvalerate, or 4.2 mg/kg body weight of ((14)C-chlorophenyl)-, ((14)C-phenoxybenzyl)-, or ((14)C-cyano)-fenvalerate. Each labeled compound was also given to two male and two female rats at a dose of 30 mg/kg body weight. Urine and feces were collected daily for 6–7 consecutive days, and carbon dioxide was collected from rats and mice that received (¹⁴C-cyano) labeled compounds. ...Two rats receiving low doses of (14C-chlorophenyl) or (14C-phenoxybenzyl)-ephedrine and fluvovallate...had an excretion half-life of... 0.5–0.6 days. ...Mice receiving the same dose levels had a radioactive excretion half-life of 0.5–0.6 days. Rats receiving 30 mg/kg body weight of (14C-chlorophenyl) or (14C-phenoxybenzyl)-ephedrine...had an excretion half-life of 0.6–0.9 days. In rats treated with lower doses of ((14)C-cyano)-cypermethrin and ephedrine, the drug excretion half-life was 1.7–2.0 days. In mice treated similarly, the drug excretion half-life was 1–1.7 days.

[1]. Anne-Marie Saillenfait, et al. The Pyrethroid Insecticides Permethrin and Esfenvalerate Do Not Disrupt Testicular Steroidogenesis in the Rat Fetus. Toxicology. 2018 Dec 1;410:116-124.

Lambda-cyhalothrin is a cyhalothrin insecticide and agrochemical. Mechanism of Action Lambda-cyhalothrin belongs to the type II synthetic pyrethroids. The main mechanism of action of pyrethroids is to interfere with the closure of voltage-dependent sodium channels, leading to repetitive neuronal firing. Following exposure, organisms may exhibit hyperexcitability, tremors, convulsions, and/or salivation, followed by drowsiness, paralysis, and death. Type II pyrethroids (containing a cyano group in the alcohol and a halogen in the acid) have also been reported to affect the presynaptic membrane of voltage-dependent calcium channels and interfere with ATPase enzymes involved in maintaining transmembrane ion concentration gradients. Interaction with sodium channels is not the only mechanism of action for pyrethroids. Their effects on the central nervous system have led many researchers to propose that their mechanisms of action may include antagonism of γ-aminobutyric acid (GABA)-mediated inhibition, regulation of nicotinic cholinergic transmission, enhancement of norepinephrine release, or action on calcium ions. Since neurotransmitter-specific drugs offer limited or only partial protection against poisoning, these effects are unlikely to be the primary mechanism of action for pyrethroids; most neurotransmitter release is secondary to increased sodium ion influx. /Pyrethroids/
We investigated the biochemical processes by which various pyrethroid insecticides altered the membrane-bound ATPase activity of the squid nervous system. Of the five ATP hydrolysis systems tested, only Ca²⁺-stimulated ATPase activity was significantly affected by pyrethroids. The natural type I pyrethroid compound, allethrin, primarily inhibited Ca²⁺-ATPase activity. Pyrethroid Compounds
This study explored the interactions of natural pyrethroids and nine other 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 all inhibited the binding of 3H-labeled perhydrohistidine toxin to the channel site in the presence of carbamoylcholine. Allethrin inhibited binding non-competitively, while 3H-labeled imipramine inhibited binding competitively, indicating that allethrin binds to the receptor channel site of imipramine. Based on their mechanism of action, pyrethroids can be divided into two classes: Class A (including allethrin) has a stronger and faster inhibitory effect on 3H-H12-HTX binding; Class B (including permethrin) has a weaker inhibitory effect, and its inhibitory efficacy increases slowly over time. Several pyrethroids exhibit high affinity for this nicotine acetylcholine receptor, suggesting that pyrethroids may possess synaptic action sites in addition to their known effects on axonal channels. /Pyrethroids and Pyrethroids/
For more complete data on the mechanisms of action of ethionyl esters (7 in total), please visit the HSDB record page.

C25H22CLNO3

419.91

419.128

66230-04-4

10342051

White crystalline solid
Colorless crystals
Clear viscous liquid at 23 °C

1.2±0.1 g/cm3

538.9±50.0 °C at 760 mmHg

59°C

279.7±30.1 °C

0.0±1.4 mmHg at 25°C

1.586

6.68

0

4

8

30

586

2

CC(C)[C@@H](C1=CC=C(C=C1)Cl)C(=O)O[C@H](C#N)C2=CC(=CC=C2)OC3=CC=CC=C3

NYPJDWWKZLNGGM-RPWUZVMVSA-N

InChI=1S/C25H22ClNO3/c1-17(2)24(18-11-13-20(26)14-12-18)25(28)30-23(16-27)19-7-6-10-22(15-19)29-21-8-4-3-5-9-21/h3-15,17,23-24H,1-2H3/t23-,24+/m1/s1

[(S)-cyano-(3-phenoxyphenyl)methyl] (2S)-2-(4-chlorophenyl)-3-methylbutanoate

Asana Esfenvalerate

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 (~238.15 mM)

Solubility in Formulation 1: 2.5 mg/mL (5.95 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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 (5.95 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 (5.95 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.)