1854 Permethrin Permethrin is only found in individuals that have used or taken this drug. It is a pyrethroid insecticide commonly used in the treatment of lice infestations and scabies. It is a yellow to light orange-brown, low melt-ing solid or viscous liquid.Permethrin acts on the nerve cell membrane to disrupt the sodium channel current by which the polarization of the membrane is regulated. Delayed repolarization and paralysis of the pests are the consequences of this disturbance. 52645-53-1 40326 C21H20Cl2O3 390.078950 Colourless crystals (L864). 34°C 220°C at 5.00E-02 mm Hg 0.006 mg/L (at 20°C) Inhalation (L857) ; oral (L857) ; dermal (L857) ; eye contact (L857). Poorly absorbed through the skin. 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) The proposed metabolic pathway for cis- and trans-permethrin are as follows. The five principle sites of metabolic attack in both permethrin isomers is ester cleavage, oxidation at the trans- and cis-methyl of the geminal dimethyl group of the acid moiety, and oxidation at 2'- and 4'- position of the phenoxy group. Conjugation of the resultant carboxylic acids, alcohols, and phenols with glucuronic acid, glycine, and sulfuric acid occurs to varying extent. cis-Permethrin is more stable then trans-permethrin, and the cis isomer yields four faecally excreted ester metabolites that results from hydroxylation at the 2'- or 4'-position of the phenoxy group or at the trans- or cis methyl group on the cyclopropane ring. The estercleaved metabolites are extensively excreted into the urine whereas the metabolites retaining an ester bond are found only in the feces. The major metabolite from the acid moiety of both isomers was Cl2CA in free (1-8%) and glucuronide (14-42%) forms. Other significant metabolites are trans-OH-Cl2CA (1-5%) and cis-OH-Cl2CA in the free (3-5%), lactone (0-4%) and glucuronide (1-2%) forms. On the other hand, the alcohol moiety released after cleavage of the ester bond of both isomers is converted mainly to the sulfate of 3-(4'-hydroxyphenoxy)benzoic acid (4'-OH-PBacid) (29-43% of the dose) and PBacid in the free (1-10%) and glucuronide (7-15%) forms. Other significant metabolites of the alcohol moiety are PBalc, PBacid-glycine and the sulfate of 3-(2'-hydroxyphenoxy) benzoic acid (2'-OH-PBacid). A study by Nakamura et al. proposed that permethrin was hydrolyzed by CES (carboxylesterase), then PBAlc formed was oxidized to PBAld, and further, PBAld was oxidized to PBAcid by the P450 system in rat liver microsomes. (A559, A256) Route of Elimination: Permethrin is rapidly metabolized by ester hydrolysis to inactive metabolites which are excreted primarily in the urine. Oral, rat LD₅₀: 430 - 4000 mg/kg Skin, rabbit LD₅₀: 2000 mg/kg LD50: 3 801 mg/kg (Oral, Rat) (L857) 3, not classifiable as to its carcinogenicity to humans. (L135) For the treatment of infestation with <i>Sarcoptes scabiei</i> (scabies). Pyrethroids are used as insecticides. (L857) Intermediate Oral: 0.2 mg/kg/day (Rat) (L857) As for every type I pyrethroids , permethrin effects typically include rapid onset of aggressive behavior and increased sensitivity to external stimuli, followed by fine tremor, prostration with coarse whole body tremor, elevated body temperature, coma, and death. Paresthesia, severe corneal damage, hypotension and tachycardia, associated with anaphylaxis can also occur following permethrin poisoning. (L857) Following oral exposure, severe fine tremor, marked reflex hyperexcitability, sympathetic activation can occur. Nausea, vomiting and abdominal pain commonly occur and develop following ingestion. Sudden bronchospasm, swelling of oral and laryngeal mucous membranes, and anaphylactoid reactions have been reported after inhalation. Hypersensitivity reactions characterized by pneumonitis, cough, dyspnea, wheezing, chest pain, and bronchospasm may occur too . Dermatitis is the main effect of a dermal exposure to permethrin. (T36) Following oral exposure, the treatment is symptomatic and supportive and includes monitoring for the development of hypersensitivity reactions with respiratory distress. Provide adequate airway management when needed. Gastric decontamination is usually not required unless the pyrethrin product is combined with a hydrocarbon. Following inhalation exposure, move patient to fresh air. monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with inhaled beta2 agonist and oral or parenteral corticosteroids. In case of eye exposure, irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist, the patient should be seen in a health care facility. If the contamination occurs through dermal exposure, remove contaminated clothing and wash exposed area thoroughly with soap and water. A physician may need to examine the area if irritation or pain persists. Vitamin E topical application is highly effective in relieving parenthesis. (T36) 2009-06-23T18:10:09Z 2014-12-24T20:24:45Z Permethrin interacts with the nicotinic acetylcholine (ACh) receptor/channel, sodium as well as calcium channels. Permethrin inhibits basal adenylate cyclase. Ca2+ ATPase (T18, L857, A258, A260). Permethrin C14388 34911 D026023 Permethrin DB04930 2174 true Liver carboxylesterase 1 (P23141) Carboxylesterase 2 (O00748) Carboxylesterase 3 (Q6UWW8) Inactive carboxylesterase 4 (Q9UKY3) Carboxylesterase 7 ( Q6NT32) Carboxylesterase 8 (Q5XG92) (T18, L857, A255, A258) CC1(C)C(C=C(Cl)Cl)C1C(=O)OCC1=CC(OC2=CC=CC=C2)=CC=C1 C21H20Cl2O3 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 InChIKey=RLLPVAHGXHCWKJ-UHFFFAOYNA-N 391.288 390.07894992 Exogenous Solid 6.5 HMDB15604 CHEMBL1525 36845