Absorption, Distribution and Excretion
The estimated rates of dermal absorption of (+) trans- and (+) cis-benzylpyrrolizide (powder or emulsifiable concentrate) in male rats were 3-7% and 8-17%, respectively. The emulsifiable concentrate was absorbed 4-5 times faster than the powder, and had a 2-3 times longer half-life (T/2) in the blood. Male Sprague-Dawley rats were orally administered (200 mg/kg) benzylpyrrolizide labeled with (14)C on an alcohol hydroxymethyl group. Absorption and elimination were rapid. Within 3 days, approximately 60% of the radioactive material was excreted in the urine and 40% in the feces. In addition to benzylpyrrolizide, 3-phenoxybenzyl alcohol and 3-phenoxybenzoic acid were also detected in the brain, liver, kidneys, and blood. Unidentified water-soluble and ether-soluble substances were also present.
The estimated rates of trans- and (+) cis-benzylpyrrolizide (powder or emulsifiable concentrate) absorption via the skin in male rats were 3-7% and 8-17%, respectively. The emulsifiable concentrate was absorbed 4-5 times faster than the powder. Almost all of the absorbed drug was excreted in urine and feces within 6 days. Following a single oral dose of 2 mg/kg (either isomer), approximately 96% of the dose was recovered from excrement within the following 6 days. The amount of (+) cis isomer excreted in feces was greater than that of (+) trans isomer, and the amount of (+) trans isomer excreted in urine was greater than that of (+) cis isomer.
Seven days after a single oral dose of 10 mg/kg body weight of (14)C-(1R, cis)- or (14)C-(1R, trans)-benzylpyrrolizide, tissue residues were generally low, but fat residues were slightly higher (1-2.5 mg/kg). Similarly, 7 days after a single oral administration of 200 mg/kg body weight of the [1R,cis] isomer, high concentrations of 14C residues (up to 23 mg/kg) were detected in fat. For more complete data on the absorption, distribution, and excretion of phenoxy ... Male Sprague-Dawley rats were orally administered a dose of mg/kg. …The urine contained low concentrations of 3-phenoxybenzoic acid and its glycine conjugate, as well as some ethers and water-soluble substances. In addition… 3-(4'-hydroxyphenoxy)benzoic acid was also present, accounting for 42.3% of the radioactivity… This compound is… the main metabolite in feces, but accounts for only… 11.9% of the radioactivity. Besides unmetabolized permethrin and unidentified water-soluble and ether-soluble substances, feces also contained 3-phenoxybenzoic acid… 3-Phenoxybenzoic acid and its glycine conjugate. 3-Phenoxybenzyl alcohol was not detected in urine or feces.
In male rats, transdermal and oral administration of powdered or emulsifiable concentrates of (+)trans and (+)cis-phenoxybenzoic acid produced almost identical metabolites. The major metabolites of the (+)trans isomer were 3-phenoxybenzoic acid and its glycine conjugate, and (3,4'-hydroxyphenoxy)benzoic acid and its sulfate. The cis isomer produced higher levels of ester metabolites.
When administered at 4, 10, or 200... When rats were administered [1R, trans]-phenoxybenzoic acid at doses of 4 mg/kg body weight (single oral dose) or 4 mg/kg body weight (oral dose for 14 consecutive days), the sulfate conjugate of 4'-hydroxyphenoxybenzoic acid was dominant, accounting for 28%, 43%, 28%, and 55% of the total dose, respectively. In addition, phenoxybenzoic acid (4%, 10%, 5%, and 6%), its glycine conjugate (1%, 3%, 2%, and 2%), its glucuronide (2%, 3%, 1%, and 3%), and free 4'-hydroxyphenoxybenzoic acid (2%, 11%, 3%, and 3%) were also detected. The sulfate conjugate of 3-(2'-hydroxyphenoxy)benzoic acid (2'-OH-PBacid) was also found to be a minor metabolite. When Sprague Dawley rats were given a single oral dose of 4 or 200 mg/kg body weight of [1R, trans]-phenoxybenzoic acid, or 4 mg/kg body weight orally for 14 consecutive days... At doses of mg/kg body weight, unmetabolized compounds were found in feces (44-45%, 44-60%, and 14-16% of the dose, respectively). An ester metabolite, a 4'-hydroxyphenoxybenzoic acid derivative of trans-phenoxybenzyl, was also detected (0.4-0.6%). For more complete data on the metabolism/metabolites of phenoxybenzyl (14 in total), please visit the HSDB record page. d-Phenoxybenzyl is a fast-acting insecticide that exerts its effects through contact and stomach poisoning. It is rapidly metabolized and excreted by the human body and has low toxicity to humans. Both the cis and trans isomers are metabolized via hydrolysis, oxidation, and conjugation, with most d-phenoxybenzyl excreted unchanged in urine and feces. After oral administration of the (1R)-trans isomer, urine is the primary route of excretion. This isomer is extensively metabolized into oxidized and conjugated derivatives of the hydrolyzed esters. Oxidation and conjugated derivatives of the (1R)-cis isomer were also found, but ester bond hydrolysis was a minor metabolic pathway. The primary excretion route for this isomer was feces. Metabolic profiles were similar after transdermal administration, although the excretion rates of the isomers differed slightly between the two routes of administration. The major metabolite was 3-phenoxybenzyl alcohol (PBalc). Additionally, trace amounts of PBacid and 4'-OH-PBacid were detected. The compound was stable under dark conditions; d-phenylephrine was relatively unstable in sunlight, ultraviolet radiation, or alkaline media. (L866, A561)

Toxicity Summary
Both type I and type II pyrethroids exert their effects by prolonging 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 closing of sodium ion channels in the nerve, thus prolonging the time it takes for the membrane potential to return to its resting state. Repetitive (sensory, motor) neuronal firing and prolonged negative afterpotentials produce effects very similar to DDT, leading to nervous system hyperactivity, which may result in paralysis and/or death. Other mechanisms of action of pyrethroids include antagonism of γ-aminobutyric acid (GABA)-mediated inhibition, regulation of nicotinic cholinergic transmission, enhancement of norepinephrine release, and action on calcium ions. They also inhibit calcium ion channels and Ca2+,Mg2+-ATPase. (T10, T18, L857)

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Toxicity Data
LD50: > 5000 mg/kg (oral, rat) (A561)
LD50: 10000 mg/kg (dermal, rat) (A561)

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Interactions
/Pyrethroid/Antidote…is important for fruit flies, but the addition of synergists…organophosphates or carbamates…may delay the antidote to ensure lethality. .../Pyrethroids/

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Non-human toxicity values
Oral LD50 in rats > 500 mg/kg
Oral LD50 in mice > 500 mg/kg
Oral LD50 in rats > 10000 mg/kg /(1R)-cis,trans isomer mixture/
Oral LD50 in mice > 10000 mg/kg /(1R)-cis,trans isomer mixture/
For more complete non-human toxicity data on pyrethroids (18 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 breastfeeding women… If used properly, 1-3 treatments usually achieve 100% efficacy… Oil-based (e.g., petroleum fraction) combinations… work fastest. …When treating head lice, apply sufficient gel, shampoo, or solution… covering the affected hair and surrounding area… After 10 minutes, thoroughly wash the hair… Repeat treatment after 7-10 days to kill any newly hatched lice. Two independent studies of pyrethroid insecticides included 101 patients with head lice, comparing the efficacy of permethrin water/alcohol shampoo, carbaryl shampoo, and malathion shampoo. Fifty subjects received a single treatment with permethrin shampoo, 28 with carbaryl shampoo, and 23 with malathion shampoo. In the comparison study of permethrin and malathion shampoo, no live lice were found on the second day after treatment, but live lice eggs were still visible in 6 subjects in the malathion shampoo group (p < 0.05). One subject still had live lice eggs visible two weeks after treatment. However, no live lice or eggs were found four weeks after treatment. Five subjects reported mild skin side effects, with no significant difference in incidence among the treatment groups. In the comparison study of permethrin and carbaryl emulsion, one subject was found to have live lice one week after treatment with permethrin emulsion. This subject did not receive further treatment, and no live lice or eggs were found during subsequent follow-up. In another case, a subject treated with permethrin emulsion developed live lice two weeks after treatment, and two subjects treated with carbaryl emulsion developed live lice four weeks after treatment. Since no live lice were found in these subjects during previous follow-ups, it is highly likely that these cases were due to reinfection from other sources.

C23H26O3

350.458

350.188

26002-80-2

D-Phenothrin;26046-85-5

4767

Colorless liquid
Pale yellow to yellow-brown clear liquid

1.1±0.1 g/cm3

437.0±45.0 °C at 760 mmHg

186.6±23.3 °C

0.0±1.0 mmHg at 25°C

1.588

7.47

0

3

7

26

512

0

O=C(C1C(C)(C)C1/C=C(C)\C)OCC2=CC=CC(OC3=CC=CC=C3)=C2

SBNFWQZLDJGRLK-UHFFFAOYSA-N

InChI=1S/C23H26O3/c1-16(2)13-20-21(23(20,3)4)22(24)25-15-17-9-8-12-19(14-17)26-18-10-6-5-7-11-18/h5-14,20-21H,15H2,1-4H3

(3-Phenoxyphenyl)methyl 2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropane-1-carboxylate

KC-1001 KC 1001KC1001 Phenothrin umithrin and d-phenothrin

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 (~285.35 mM)

Solubility in Formulation 1: 2.5 mg/mL (7.13 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 (7.13 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 (7.13 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.)