Permethrin: Difference between revisions

Permethrin

Names
IUPAC name 3-Phenoxybenzyl (1RS)-cis,trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate
Identifiers
CAS Number	52645-53-1 Y
3D model (JSmol)	Interactive image
ChEBI	CHEBI:34911 Y
ChEMBL	ChEMBL1525 Y
ChemSpider	36845 Y
DrugBank	DB04930 Y
ECHA InfoCard	100.052.771
KEGG	C14388 Y
PubChem CID	40326
UNII	509F88P9SZ Y
CompTox Dashboard (EPA)	DTXSID8022292
InChI InChI=1S/C21H20Cl2O3/c1-21(2)17(12-18(22)23)19(21)20(24)25-13-14-7-6-10-16(11-14)26-15-8-4-3-5-9-15/h3-12,17,19H,13H2,1-2H3 Y Key: RLLPVAHGXHCWKJ-UHFFFAOYSA-N Y InChI=1/C21H20Cl2O3/c1-21(2)17(12-18(22)23)19(21)20(24)25-13-14-7-6-10-16(11-14)26-15-8-4-3-5-9-15/h3-12,17,19H,13H2,1-2H3 Key: RLLPVAHGXHCWKJ-UHFFFAOYAS
SMILES Cl/C(Cl)=C/C3C(C(=O)OCc2cccc(Oc1ccccc1)c2)C3(C)C
Properties
Chemical formula	C21H20Cl2O3
Molar mass	391.29 g·mol−1
Appearance	Colorless crystals
Density	1.19 g/cm³, solid
Melting point	34 °C (93 °F; 307 K)
Boiling point	200 °C (392 °F; 473 K)
Solubility in water	5.5 x 10−3 ppm
Hazards
Occupational safety and health (OHS/OSH):
Main hazards	Irritating to skin and eyes, damaging to lungs
Related compounds
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Y verify (what is YN ?) Infobox references

Permethrin is a common synthetic chemical, widely used as an insecticide, acaricide, and insect repellent. It belongs to the family of synthetic chemicals called pyrethroids and functions as a neurotoxin, affecting neuron membranes by prolonging sodium channel activation. It is not known to rapidly harm most mammals or birds, but is dangerously toxic to fish and to cats: in cats it may induce hyperexcitability, tremors, seizures, and even death.^[1] In general, it has a low mammalian toxicity and is poorly absorbed by skin.^[2]

In medicine, permethrin is a first-line treatment for scabies; a 5% (w/w) cream is marketed by Johnson & Johnson under the name Lyclear. In Nordic countries and North America, it is marketed under trade name Nix, often available over the counter.

It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.^[3]

Permethrin is used:

• as an insecticide
  • in agriculture, to protect crops
  • in agriculture, to kill livestock parasites
  • for industrial/domestic insect control
• as an insect repellent or insect screen
  • in timber treatment
  • as a personal protective measure (cloth impregnant, used primarily for US military uniforms and mosquito nets)
  • in pet flea preventative collars or treatment.

In agriculture, permethrin is mainly used on cotton, wheat, maize, and alfalfa crops. Its use is controversial because, as a broad-spectrum chemical, it kills indiscriminately; as well as the intended pests, it can harm beneficial insects including honey bees, and aquatic life.^[4]

Permethrin kills ticks on contact with treated clothing. A method of reducing deer tick populations by treating rodent vectors involves stuffing biodegradable cardboard tubes with permethrin-treated cotton. Mice collect the cotton for lining their nests. Permethrin on the cotton instantly kills any immature ticks that are feeding on the mice. It is important to put the tubes where mice will find them, such as in dense, dark brush, or at the base of a log; mice are unlikely to gather cotton from an open lawn.

Permethrin is used in tropical areas to prevent mosquito-borne disease such as dengue fever and malaria. Mosquito nets used to cover beds may be treated with a solution of permethrin. This increases the effectiveness of the bed net by killing parasitic insects before they are able to find gaps or holes in the net. Military personnel training in malaria-endemic areas may be instructed to treat their uniforms with permethrin, as well. An application should last several washes.

Permethrin is available for topical use as a cream or lotion. It is indicated for the treatment and prevention in exposed individuals of head lice (Pediculus humanus capitis) and treatment of scabies (Sarcoptes scabies).^[5] Permethrin formulations include a prescription-only 5% strength for scabies and an over-the-counter 1% strength for lice.

For treatment of scabies: Adults and children older than 2 months are instructed to apply the cream to the entire body from head to the soles of the feet. Wash off the cream after 8–14 hours. In general, one treatment is curative.^[6]

For treatment of head lice: Apply to hair, scalp, and neck after shampooing. Leave in for 10 minutes and rinse. Avoid contact with eyes.^[7]

Permethrin application can cause mild skin irritation and burning. Discontinue use if hypersensitivity occurs.

Permethrin has little systemic absorption, and is considered safe for topical use in adults and children over the age of 2 months. The FDA has assigned it as pregnancy category B. Animal studies have shown no effects on fertility or teratogenicity, but studies in humans have not been performed. The excretion of permethrin in breastmilk is unknown, and breastfeeding is recommended to be temporarily discontinued during treatment.^[7]

Absorption of topical permethrin is minimal. One in vivo study demonstrated 0.5% absorption in the first 48 hours based upon excretion of urinary metabolites.^[8]

Distribution of permethrin has been studied in rat models, with highest amounts accumulating in fat and the brain.^[9] This can be explained by the lipophilic nature of the permethrin molecule.

Metabolism of permethrin occurs mainly in the liver, where the molecule undergoes oxidation by the cytochrome p450 system, as well as hydrolysis, into metabolites.^[8] Elimination of these metabolites occurs via urinary excretion.

To better protect soldiers from the risk and annoyance of biting insects, the US^[10] and British^{[citation needed]} armies are treating all new uniforms with permethrin.

Permethrin has four stereoisomers (two enantiomeric pairs), arising from the two stereocentres in the cyclopropane ring. The trans enantiomeric pair is known as transpermethrin.

• 
  (1S)-trans-acid moiety
• 
  (3S)-trans-acid moiety
• 
  one cis enantiomer
• 
  the other cis enantiomer

Permethrin acts as a neurotoxin, slowing down the nervous system through binding to sodium channels. This action is negatively correlated to temperature, thus, in general, showing more acute effects on cold-blooded animals (insects, fish, frogs, etc.) over warm-blooded animals (mammals and birds):

• Permethrin is extremely toxic to fish and aquatic life in general, so extreme care must be taken when using products containing permethrin near water sources.
• Permethrin is also highly toxic to cats, and flea and tick-repellent formulas intended and labeled for (the more resistant) dogs may contain permethrin and cause feline permethrin toxicosis in cats.^[11]
• Very high doses will have tangible neurotoxic effects on mammals and birds, including human beings.

Permethrin is listed as a "restricted use" substance by the US Environmental Protection Agency (EPA)^[12] due to its high toxicity to aquatic organisms,^[13] so permethrin and permethrin-contaminated water should be properly disposed. Permethrin is quite stable, having a half life of 51–71 days in an aqueous environment exposed to light. It is also highly persistent in soil.^[14]

According to the Connecticut Department of Public Health, permethrin "has low mammalian toxicity, is poorly absorbed through the skin, and is rapidly inactivated by the body. Skin reactions have been uncommon."^[15]

Excessive exposure to permethrin can cause nausea, headache, muscle weakness, excessive salivation, shortness of breath, and seizures. Worker exposure to the chemical can be monitored by measurement of the urinary metabolites, while severe overdosage may be confirmed by measurement of permethrin in serum or blood plasma.^[16]

Permethrin does not present any notable genotoxicity or immunotoxicity in humans and farm animals, but is classified by the EPA as a likely human carcinogen, based on reproducible studies in which mice fed permethrin developed liver and lung tumors.^[17] Carcinogenic action in nasal mucosal cells due to inhalation exposure is suspected, due to observed genotoxicity in human tissue samples, and in rat livers the evidence of increased preneoplastic lesions raises concern over oral exposure.^[18][19]

Animal studies by Bloomquist et al.^[20] suggest a possible link of permethrin exposure to Parkinson's disease, including very small exposures:

2002 study – "Our studies have documented low-dose effects of permethrin, doses below one-one thousandth of a lethal dose for a mouse, with effects on those brain pathways involved in Parkinson's disease [...] We have found effects consistent with a pre-parkinsonsian condition, but not yet full-blown parkinsonism." ^[21][22]

However, a 2007 study by the same researcher concluded "little hazard to humans" existed.

2007 study – "long-term, low-dose exposure to permethrin alone did not cause signs of neurotoxicity to striatal dopaminergic neural terminals, or enhance the effects of MPTP. We conclude that, under typical use conditions, permethrin poses little parkinsonian hazard to humans, including when impregnated into clothing for control of biting flies"^[23]

A 2006 study in South Africa found residues of permethrin in breast milk in an area that experienced the use of pyrethroids in small-scale agriculture.^[24]

Pesticide-grade permethrin is toxic to cats. Many cats die after being given flea treatments intended for dogs, or by contact with dogs having recently been treated with permethrin.^[25]

• Methoprene
• Pyrethrin
• Pyrethrum

• Pesticide Properties Database (PPDB) record for Permethrin
• Permethrin Technical Fact Sheet – National Pesticide Information Center
• Permethrin General Fact Sheet – National Pesticide Information Center
• Permethrin-treated Clothing Hot Topic – National Pesticide Information Center
• "Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms", National Research Council (1994, US)
• "Permethrin summary report", Committee for Veterinary Products, European Agency for the Evaluation of Medical Products (1998, EU)
• Pesticide link to Parkinson Disease
• Permethrin Pesticide Information Profile – Extension Toxicology Network
• Permethrin chemical data