In animal modeling, fenpropathrin can be used to create models of Parkinson's disease.

Absorption, Distribution and Excretion
/PYRETHROIDS/ READILY PENETRATE INSECT CUTICLE AS SHOWN BY TOPICAL LD50 TO PERIPLANETA (COCKROACH) ... /PYRETHROIDS/
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/

---

Metabolism / Metabolites
Metabolism of fenproponate in rats involves rapid oxidase catalyzed ester cleavage followed by hydroxylation.
The metabolic pathways for the breakdown of the pyrethroids vary little between mammalian species but vary somewhat with structure. ... Essentially, pyrethrum & allethrin are broken down mainly by oxidation of the isobutenyl side chain of the acid moiety & of the unsaturated side chain of the alcohol moiety with ester hydrolysis playing & important part, whereas for the other pyrethroids ester hydrolysis predominates. /Pyrethrum and pyrethroids/
The relative resistance of mammals to the pyrethroids is almost wholly attributable to their ability to hydrolyze the pyrethroids rapidly to their inactive acid & alcohol components, since direct injection into the mammalian CNS leads to a susceptibility similar to that seen in insects. Some additional resistance of homeothermic organisms can also be attributed to the negative temperature coefficient of action of the pyrethroids, which are thus less toxic at mammalian body temperatures, but the major effect is metabolic. Metabolic disposal of the pyrethroids is very rapid, which means that toxicity is high by the iv route, moderate by slower oral absorption, & often unmeasureably low by dermal absorption. /Pyrethroids/
FASTEST BREAKDOWN IS SEEN WITH PRIMARY ALCOHOL ESTERS OF TRANS-SUBSTITUTED ACIDS SINCE THEY UNDERGO RAPID HYDROLYTIC & OXIDATIVE ATTACK. FOR ALL SECONDARY ALCOHOL ESTERS & FOR PRIMARY ALCOHOL CIS-SUBSTITUTED CYCLOPROPANECARBOXYLATES, OXIDATIVE ATTACK IS PREDOMINANT. /PYRETHROIDS/
For more Metabolism/Metabolites (Complete) data for FENPROPATHRIN (7 total), please visit the HSDB record page.
Fenpropathrin has been shown to be well absorbed after oral administration, extensively metabolized, and eliminated as polar conjugates in urine. The main route of metabolism was, as anticipated, via hydrolysis of the ester linkage. The cyclopropane-carboxylic acid moiety was subsequently excreted via the urine as the glucuronide conjugate. (L857)

Toxicity Summary
Pyrethroids exert their effect by prolonging the open phase of the sodium channel gates when a nerve cell is excited. They appear to bind to the membrane lipid phase in the immediate vicinity of the sodium channel, thus modifying the channel kinetics. This blocks the closing of the sodium gates in the nerves, and thus prolongs the return of the membrane potential to its resting state. The repetitive (sensory, motor) neuronal discharge and a prolonged negative afterpotential produces effects quite similar to those produced by DDT, leading to hyperactivity of the nervous system which can result in paralysis and/or death. Other mechanisms of action of pyrethroids include antagonism of gamma-aminobutyric acid (GABA)-mediated inhibition, modulation of nicotinic cholinergic transmission, enhancement of noradrenaline release, and actions on calcium ions. (T18, L857)

---

Toxicity Data
LC50 (rat) > 19,070,000 mg/m3/4h
LD50: 70.6 mg/kg (Oral, Rat) (T58)

---

Interactions
/Pyrethroid/ detoxification ... important in flies, may be delayed by the addition of synergists ... organophosphates or carbamates ... to guarantee a lethal effect. ... /Pyrethroid/
Piperonyl butoxide potentiates /insecticidal activity/ of pyrethrins by inhibiting the hydrolytic enzymes responsible for pyrethrins' metabolism in arthropods. When piperonyl butoxide is combined with pyrethrins, the insecticidal activity of the latter drug is increased 2-12 times /Pyrethrins/
At dietary level of 1000 ppm pyrethrins & 10000 ppm piperonyl butoxide ... /enlargement, margination, & cytoplasmic inclusions in liver cells of rats/ were well developed in only 8 days, but ... were not maximal. Changes were proportional to dosage & similar to those produced by DDT. Effects of the 2 ... were additive. /Pyrethrins/

---

Non-Human Toxicity Values
LD50 Rat male oral 70.6 mg/kg (in corn oil)
LD50 Rat female oral 66.7 mg/kg (in corn oil)
LD50 Rat male percutaneous 1000 mg/kg
LD50 Rat female percutaneous 870 mg/kg
LD50 Rabbit percutaneous >2000 mg/kg

[1]. Jing Xiong, et al. Fenpropathrin, a Widely Used Pesticide, Causes Dopaminergic Degeneration. Mol Neurobiol. 2016 Mar;53(2):995-1008.

Yellowish to brown liquid or solid, depending on purity and temperature. Used as an acaricide and insecticide.
Fenpropathrin is a cyclopropanecarboxylate ester obtained by formal condensation between 2,2,3,3-tetramethylcyclopropanecarboxylic acid and cyano(3-phenoxyphenyl)methanol. It has a role as a pyrethroid ester insecticide, a pyrethroid ester acaricide and an agrochemical. It is an aromatic ether and a cyclopropanecarboxylate ester. It is functionally related to a 2,2,3,3-tetramethylcyclopropanecarboxylic acid.
Fenpropathrin is a pyrethroid (type 1) 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. Insects with certain mutations in their sodium channel gene may be resistant to pyrethroid insecticides. (L811, L708)

---

Mechanism of Action
The synthetic pyrethroids delay closure of the sodium channel, resulting in a sodium tail current that is characterized by a slow influx of sodium during the end of depolarization. Apparently the pyrethroid molecule holds the activation gate in the open position. Pyrethroids with an alpha-cyano group (e.g., fenvalerate) produce more prolonged sodium tail currents than do other pyrethroids (e.g., permethrin, bioresmethrin). The former group of pyrethroids causes more cutaneous sensations than the latter. /Synthetic pyrethroids/
Interaction with sodium channels is not the only mechanism of action proposed for the pyrethroids. Their effects on the CNS have led various workers to suggest actions via antagonism of gamma-aminobutyric acid (GABA)-mediated inhibition, modulation of nicotinic cholinergic transmission, enhancement of noradrenaline release, or actions on calcium ions. Since neurotransmitter specific pharmacological agents offer only poor or partial protection against poisoning, it is unlikely that one of these effects represents the primary mechanism of action of the pyrethroids, & most neurotransmitter release is secondary to increased sodium entry. /Pyrethroids/
The symptoms of pyrethrin poisoning follow the typical pattern ... : (1) excitation, (2) convulsions, (3) paralysis, and (4) death. The effects of pyrethrins on the insect nervous system closely resemble those of DDT, but are apparently much less persistent. Regular, rhythmic, and spontaneous nerve discharges have been observed in insect and crustacean nerve-muscle preparations poisoned with pyrethrins. The primary target of pyrethrins seems to be the ganglia of the insect central nervous system although some pyrethrin-poisoning effect can be observed in isolated legs. /Pyrethrins/
Electrophysiologically, pyrethrins cause repetitive discharges and conduction block. /Pyrethrins/
For more Mechanism of Action (Complete) data for FENPROPATHRIN (12 total), please visit the HSDB record page.

---

Therapeutic Uses
Pyrethrins with piperonyl butoxide are used for topical treatment of pediculosis (lice infestations). Combinations of pyrethrins with piperonyl butoxide are not effective for treatment of scabies (mite infestations). Although there are no well-controlled comparative studies, many clinicians consider 1% lindane to be pediculicide of choice. However, some clinicians recommend use of pyrethrins with piperonyl butoxide, esp in infants, young children, & pregnant or lactating women ... . If used correctly, 1-3 treatments ... are usually 100% effective ... Oil based (eg, petroleum distillate) combinations ... produce the quickest results. ... For treatment of pediculosis, enough gel, shampoo, or solution ... should be applied to cover affected hair & adjacent areas ... After 10 min, hair is ... washed thoroughly ... treatment should be repeated after 7-10 days to kill any newly hatched lice. /Pyrethrins/

C22H23NO3

349.43

349.167

39515-41-8

Fenpropathrin-d5

47326

Pale yellow oil
Yellow brown liquid or solid

1.1±0.1 g/cm3

448.2±35.0 °C at 760 mmHg

50 - 51ºC

195.5±16.2 °C

0.0±1.1 mmHg at 25°C

1.552

5.48

0

4

6

26

553

0

CC1(C)C(C(=O)OC(C#N)C2=CC(=CC=C2)OC3=CC=CC=C3)C1(C)C

XQUXKZZNEFRCAW-UHFFFAOYSA-N

InChI=1S/C22H23NO3/c1-21(2)19(22(21,3)4)20(24)26-18(14-23)15-9-8-12-17(13-15)25-16-10-6-5-7-11-16/h5-13,18-19H,1-4H3

[cyano-(3-phenoxyphenyl)methyl] 2,2,3,3-tetramethylcyclopropane-1-carboxylate

Fenpropathrin XE-938 S 3206

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 (~286.19 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.15 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.

---

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