Permethrin

Pesticides

Pesticide -> EPA IRIS

Insecticides

Active substance -> EU Pesticides database: Not approved

Pesticides -> Pyrethrins/Pyrethroids

Pesticide

log Kow = 6.50

6.50

6.5

1.19 - 1.27 at 20 °C

Relative density (water = 1): 1.2

Colorless crystals to a viscous liquid; Color, white to pale yellow

Pure permethrin cis-isomer forms colorless crystals at room temperature but a mixture of cis and trans isomers normally occurs as a liquid, with its appearance depending on the ratio of isomers. Pure permethrin (40:60) is a colorless, viscous liquid, whereas the technical compound is a yellow to yellow-brown viscous liquid.

In water, 0.0111 mg/L at 20 °C, pH 7.0-9.3 (OECD Method 105)

In water, 6.00X10-3 mg/L (pH 7, 20 °C); cis-isomers 0.20 mg/L (25 °C); trans-isomers 0.13 mg/L (25 °C)

In xylene and hexane >1000, methanol 258 (all in g/kg at 25 °C)

Soluble in most organic solvents except ethylene glycol. Soluble in acetone, ethanol, ether, and xylene

In water, 6.00X10-3 mg/ml @ 20 °C.

Breast Feeding; Lactation; Milk, Human; Anti-Infective Agents; Antiparasitic Agents; Insecticides

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Dermatological medicines > Scabicides and pediculicides

>290 °C at 760 mm Hg

BP: 200 °C at 0.1 mm Hg

Warning

H302: Harmful if swallowed [Warning Acute toxicity, oral]

P261, P264, P270, P271, P272, P273, P280, P301+P317, P302+P352, P304+P340, P317, P321, P330, P333+P317, P362+P364, P391, and P501 (click each P-code to see the statement)

This chemical does not meet GHS hazard criteria for 0.2% (1 of 519) of reports.

Warning

H302+H332 (13.5%): Harmful if swallowed or if inhaled [Warning Acute toxicity, oral; acute toxicity, inhalation]

Chemical: Cyclopropanecarboxylic acid, 3-(2,2-dichloroethenyl)-2,2-dimethyl-, (3-phenoxyphenyl)methyl ester

Permethrin is listed in the dataset of EPA Human Health Benchmarks for Pesticides under the Safe Drinking Water Act (40 eCFR 141)

00/817/EC

Permethrin: HSNO Approval: HSR003111 Approved with controls

The New Jersey Worker and Community Right to Know Act requires public and private employers to provide information about hazardous substances at their workplaces. (N.J.S.A. 34:5A-1 et. seq.)

Excerpt from ERG Guide 171 [Substances (Low to Moderate Hazard)]:

Combustible. Liquid formulations containing organic solvents may be flammable. Gives off irritating or toxic fumes (or gases) in a fire.

A skin, eye, and respiratory tract irritant; [ICSC] May be a skin sensitizer; [eChemPortal: ESIS] May cause irritation; May cause skin sensitization; Targets the CNS in high-dose animal studies; [MSDSonline] Rapidly metabolized; Does not accumulate in body; Causes hyperactivity and tremors in high-dose feeding studies of experimental animals; Exposed workers complain of skin and eye irritation; No skin sensitization in animal studies; [INCHEM PDS: Permethrin] See Imiprothrin.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including permethrin, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

USEPA/Office of Prevention, Pesticides and Toxic Substances; Reregistration Eligibility Decision Document - Permethrin EPA 738-R-09-306 (May 2009). The RED summarizes the risk assessment conclusions and outlines any risk reduction measures necessary for the pesticide to continue to be registered in the U.S.[Available from, as of January 27, 2014: http://www.epa.gov/pesticides/reregistration/status.htm]

U.S. Dept Health & Human Services/Agency for Toxic Substances & Disease Registry; Toxicological Profile for Pyrethrins and Pyrethroids (September 2003) PB2004-100004). The ATSDR toxicological profile succinctly characterizes the toxicologic and adverse health effects information for the hazardous substance described here. Each peer-reviewed profile identifies and reviews the key literature that describes a hazardous substance's toxicologic properties. Other pertinent literature is also presented, but is described in less detail than the key studies.[Available from, as of March 11, 2014: http://www.atsdr.cdc.gov/toxprofiles/index.asp]

Clark JR et al; Toxicity of Pyrethroids to Marine Invertebrates and Fish: A Literature Review and Test Results with Sediment-Sorbed Chemicals. Environ Toxicol Chem 8 (5): 393-401 (1989). Data on acute and chronic toxicity of permethrin, fenvalerate, cypermethrin, and flucythinate to marine invertebrates and fishes are reviewed.

Mian LS, Mulla MS; Effects of Pyrethroid Insecticides on Nontarget Invertebratesin Aquatic Ecosystems. J Agric Entomol 9 (2): 73-98 (1992). This review presents data on the impacts of pyrethroid insecticides on nontarget aquatic invertebrates.

For more Special Reports (Complete) data for PERMETHRIN (10 total), please visit the HSDB record page.

Tolerances are established for the combined residues of the insecticide cis- and trans-permethrin isomers [cis-(3-phenoxyphenyl)methyl 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane carboxylate] and [trans-(3-phenoxyphenyl)methyl 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane carboxylate] in/on the following food commodities:[Table#6277]

Tolerances with regional registration, as defined in section 180.1(l) are established for the combined residues of the insecticide cis- and trans-permethrin isomers [cis-(3-phenoxyphenyl)methyl 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane carboxylate] and [trans-(3-phenoxyphenyl)methyl 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane carboxylate] in/on the following food commodities:[Table#6278]

The Agency has completed its assessment of the dietary, occupational, residential, and ecological risk associated with the use of pesticide products containing the active ingredient permethrin. Based on a review of these data and on public comments on the Agency's assessments for the active ingredient permethrin, the Agency has sufficient information on the human health and ecological effects to make decisions as part of the tolerance reassessment process under FFDCA and reregistration process under FIFRA, as amended by FQPA. The Agency has determined that permethrin-containing products are eligible for reregistration provided that: (i) the risk mitigation measures outlined in this document are adopted and (ii) label amendments are made to reflect these measures. ... Based on its evaluation of permethrin, the Agency has determined that permethrin products, unless labeled and used as specified in this document, would present risks inconsistent with FIFRA. Accordingly, should a registrant fail to implement any of the risk mitigation measures identified in this document, the Agency may take regulatory action to address the risk concerns from the use of permethrin. If all changes outlined in this document are incorporated into the product labels, then all current risks for permethrin will be adequately mitigated for the purposes of this determination under FIFRA.

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their continued use. Under this pesticide reregistration program, EPA examines newer health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether the use of the pesticide does not pose unreasonable risk in accordance to newer saftey standards, such as those described in the Food Quality Protection Act of 1996. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA '88 were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern than those on List C, and with List C containing pesticides of greater concern than those on List D. Permethrin is found on List B. Case No: 2510; Pesticide type: Insecticide; Case Status: OPP is reviewing data from the pesticide's producers regarding its human health and/or environmental effects, or OPP is determining the pesticide's eligibility for reregistration and developing the Reregistration Eligibility Decision (RED) document.; Active ingredient (AI): 3-(Phenoxyphenyl)methyl (+-)cis,trans-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate; Data Call-in (DCI) Date(s): 08/09/91, 01/02/92, 04/11/94, 03/03/95, 10/13/95; AI Status: The producers of the pesticide has made commitments to conduct the studies and pay the fees required for reregistration, and are meeting those commitments in a timely manner.

Excerpt from ERG Guide 171 [Substances (Low to Moderate Hazard)]:

Use powder, AFFF, foam, carbon dioxide. In case of fire: keep drums, etc., cool by spraying with water.

Fresh air, rest.

Remove contaminated clothes. Rinse and then wash skin with water and soap.

First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.

Rinse mouth. Refer for medical attention .

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal and plant life; and conformance with environmental and public health regulations.

Personal protection: filter respirator for organic gases and particulates adapted to the airborne concentration of the substance. Do NOT wash away into sewer. Do NOT let this chemical enter the environment. Sweep spilled substance into covered containers. If appropriate, moisten first to prevent dusting. Carefully collect remainder. Then store and dispose of according to local regulations.

Avoid contact with eyes, skin, or clothing. Avoid breathing vapor or spray mist. Wash thoroughly after handling.

SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

Mixing /of permethrin/, if not mechanical, should always be carried out with a paddle of appropriate length. Avoid contact with mouth and eyes. Before eating, drinking or smoking, hands and other exposed skin should be thoroughly washed with alkaline soap.

The concentration of permethrin in the urine of an agricultural worker exposed to the pesticide during application to cabbage was 0 (before application), 0 (after application), 1.8 (6 hrs), 2.8 (17 hrs), 1.4 (26 hrs), 1.9(30 hrs), and 1.6 (40 hrs) ng/mg(1). A person who packed conifer seedlings for 6 hrs in a tunnel in Sweden (whose face was close to the plants) excreted 0.26 ug/mL permethrin acid metabolite in the urine the following morning; in the afternoon, excretion was below the detection limit(2).

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)

The effects of pyrethroids were studied on phosphoinositide breakdown in guinea pig synaptoneurosomes. Similar to other agents that activate voltage-dependent sodium channels, type I and type II pyrethroids stimulated phosphoinositide breakdown. Type II pyrethroids, like deltamethrin and fenvalerate, were more potent and, at least for deltamethrin, more efficacious than type I pyrethroids, like allethrin, resmethrin and permethrin. The effects of type II pyrethroids could be partially inhibited by the sodium channel blocker tetrodotoxin. The effects of allethrin and resmethrin were not affected by 5 microM tetrodotoxin. Stimulation of phosphoinositide breakdown by fenvalerate was additive to the stimulation elicited by the receptor agonists carbamylcholine and norepinephrine, but not to the stimulation elicited by sodium channel agents (batrachotoxin, scorpion venom and pumiliotoxin B). Stimulation by allethrin was not additive to the stimulation elicited either by receptor agonists or sodium channel agents. A submaximal concentration of allethrin, a type I pyrethroid, did not greatly affect the dose-dependent stimulation elicited by a type II pyrethroid, deltamethrin, while a higher concentration of allethrin prevented further stimulation by type II pyrethroids. A local anesthetic, dibucaine, which inhibits sodium channel activation, inhibited phosphoinositide breakdown induced by type II, but not by type I pyrethroids, except at higher concentrations. Thus, type II pyrethroids appear to stimulate phosphoinositide breakdown in synaptoneurosomes in a manner analogous to other sodium channel agents, while type I pyrethroids elicit phosphoinositide breakdown by a different mechanism, probably not involving sodium channels.

/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 and 10000 ppm piperonyl butoxide ... /enlargement, margination, and cytoplasmic inclusions in liver cells of rats/ were well developed in only 8 days, but ... were not maximal. Changes were proportional to dosage and similar to those produced by DDT. Effects of the 2 ... were additive. /Pyrethrins/

/Nuclear magnetic resonance/ (NMR) combined with pattern recognition was recently introduced as a new technique for rapid xenobiotic toxicity evaluation. In this article, metabolic changes in the biofluid of rats after 90-day oral treatment with propoxur, permethrin and a combination of these two pesticides were investigated. Propoxur dosing induced increased urinary taurine, creatinine and glucose, whereas urinary lactate and acetate were increased in the highest permethrin dose group. Urinary acetate, alanine, lactate and trimethylamine levels were increased in the mixture group, accompanied by decreased urinary tricarboxylic acid cycle intermediates. In addition, the highest dose of the mixture displayed raised 3-D-hydroxybutyrate, acetate and lactate levels in the serum sample. Chronic exposure to a combination of propoxur and permethrin may induce hepatotoxicity and nephrotoxicity. An increase in acetate, alanine and formate in the urine could be a potentially sensitive biomarker of the chronic, combined effects of permethrin and propoxur.

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)

LD50; Species: Anas platyrhynchos (Mallard Duck) age 19 months; oral via capsule >2000 mg/kg

LC50; Species: Anas platyrhynchos (Mallard Duck) age 7 days; diet (chemical incorporated into food) >5200 ppm for 8 days

LD50; Species: Anas platyrhynchos (Mallard Duck) adult; oral via capsule >9868 mg/kg

LD50; Species: Anas platyrhynchos (Mallard Duck) age 14 days; oral via capsule >4640 mg/kg

For more Ecotoxicity Values (Complete) data for PERMETHRIN (55 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), Koc values ranging from 10,471 to 86,000(2), indicate that permethrin is expected to be immobile in soil(SRC). Volatilization of permethrin from moist soil surfaces is possible(SRC) given an estimated Henry's Law constant of 2.4X10-6 atm-cu m/mole(SRC), derived from its vapor pressure, 5.18X10-8 mm Hg(3), and water solubility, 0.0111 mg/L(3). However, adsorption to soil is expected to attenuate volatilization(SRC). Permethrin is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure. Permethrin is susceptible to biodegradation in soil and sediment as demonstrated by incubation studies using sterile and non-sterile conditions(4,5). Degradation in soil and sediments occurs through biodegradation and abiotic hydrolysis(6). Permethrin is susceptible to direct photolysis on soil surfaces exposed to sunlight(3); cis- and trans-permethrin photolysis half-lives of 23.1 and 36.8 days have been measured in water respectively(3). The degradation half-life of permethrin in aerobically incubated soil was less than 4 weeks, and the degradation of the trans-isomer was more rapid than the cis-isomer(7). Faster degradation of the trans-isomers versus the cis-isomers was also observed in soil and sediment studies(8). In two Japanese soils, both the 1R, trans- and 1R, cis-isomers were rapidly degraded under dry conditions with half-lives of less than 2 days(9). Under anaerobic conditions in flooded silt loam soils, degradation half-lives were 32-34 days for 14C-labeled trans-permethrin and greater than 64 days for 14C-labeled cis-permethrin(7). Field dissipation half-lives for permethrin generally fall in the range from 6 to 106 days with 42 days as a selected value for modeling(2). Under aerobic conditions, the field dissipation half-life is roughly 30 days (4-40 day range) and under anaerobic conditions, the field dissipation half-life is roughly 108 days (3-204 day range)(2).

AQUATIC FATE: Based on a classification scheme(1), Koc values ranging from 10,471 to 86,000(2), indicate that permethrin is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is possible(3) based upon an estimated Henry's Law constant of 2.2X10-6 atm-cu m/mole(SRC), derived from its vapor pressure, 5.18X10-8 mm Hg(4), and water solubility, 0.00111 mg/L(4). Using this Henry's Law constant and an estimation method(5), volatilization half-lives for a model river and model lake are 39 days and 289 days, respectively(SRC). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column(SRC). The estimated volatilization half-life from a model pond exceeds 100 years if adsorption is considered(6). According to a classification scheme(7), BCF values of approximately 560 and 480 for rainbow trout (Oncorhynchus mykiss) and sheepshead minnow (Cyprinodon vagiegatus), respectively(8,9), suggests the potential for bioconcentration in aquatic organisms is high(SRC). At pH 4, pH 5 and pH 7 (25 °C), permethrin is stable towards abiotic hydrolysis(2,4). At pH 9, the abiotic hydrolysis rate constant is 0.0139 per day at 25 °C(2) which corresponds to a half-life of 50 days(SRC). The hydrolysis half-lives of cis- and trans-permethrin at pH 9(25 °C, sterile water) have been measured as 42.3 and 37.7 days respectively(4). In water, a photolysis rate constant of 0.021 per day has been reported(2) which corresponds to photodegradation half-life of 33 days(SRC). In sterile buffer solutions (pH 4) exposed to irradiation equivalent to natural sunlight (Tokyo, 35 deg N, April-June), cis- and trans-permethrin had photolysis half-lives of 23.1 and 38.6 days respectively(4); using synthetic humic water, the photolysis half-lives decreased to 14.6 and 25.5 days respectively(2). The photolysis half-life of permethrin in seawater exposed to outdoor light was determined to be 14 days(9). Photolysis half-lives of 27.1 and 19.6 hrs were determined for respective cis- and trans-isomers in 800 mL pond water exposed to sunlight(10). Faster photodegradation in humic and natural waters can result from reaction with photo-oxidant species such hydroxyl radicals, peroxy radicals and singlet oxygen(11). Permethrin is susceptible to biodegradation as demonstrated by incubation studies using sterile and non-sterile conditions(9,12). The biodegradation half-life of permethrin in a sediment-seawater solution was less than 2.5 days(9); under sterile conditions there was no significant change in permethrin concentration(9).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), permethrin, which has a vapor pressure of 5.18X10-8 mm Hg at 25 °C(2), will exist in both the vapor and particulate phases in the ambient atmosphere(SRC). Vapor-phase permethrin is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals and ozone(SRC); the half-life for reaction with hydroxyl radicals in air is estimated to be 17 hours(SRC), calculated from its rate constant of 2.3X10-11 cu cm/molecule-sec at 25 °C(3); the half-life for reaction with ozone in air is estimated to be 49 days(SRC), calculated from its rate constant of 2.3X10-19 cu cm/molecule-sec at 25 °C(3). Particulate-phase permethrin may be removed from the air by wet and dry deposition(SRC). Permethrin absorbs light in the environmental spectrum(4) and has been shown to photodegrade in sunlight(2); therefore, permethrin can degrade through direct photolysis(SRC).

During October 1, 1981 and September 30, 1986, permethrin was found in 309 U.S. agricultural commodity samples at a concentration range of >0-0.05 ppm, 155 samples at 0.05-0.1 ppm, 283 samples at 0.1-0.5 ppm, 104 samples at 0.5-1.0 ppm, 51 samples at 1.0-2.0 ppm, and 17 agricultural commodity samples at a concentration >2.0 ppm(1). This study does not distinguish between domestic and imported commodities or between surveillance and compliance samples(1). During October 1, 1981 and September 30, 1986, permethrin was found in 89 U.S. domestic agricultural commodities conducted by surveillance sampling at a concentration range of >0-0.05 ppm, 75 samples at 0.05-0.1 ppm, 217 samples at 0.1-0.5 ppm, 100 samples at 0.5-1.0 ppm, 47 samples at 1.0-2.0 ppm, and 11 domestic agricultural commodities at a concentration >2.0 ppm(2). During October 1, 1981 and September 30, 1986, permethrin was found in 234 U.S. imported agricultural commodities conducted by surveillance sampling at a concentration range of >0-0.05 ppm, 97 samples at 0.05-0.1 ppm, 36 samples at 0.1-0.5 ppm,1 sample at 0.5-1.0 ppm, and 1 imported agricultural commodity sample at a concentration 1.0-2.0 ppm(2). As part of the FDA Total Diet Study in 1992-1993, the max concentration of permethrin (total) in domestic and imported tomatoes was 0.28 ppm (24% of samples) and 0.38 ppm (26% of samples), respectively(3); the average concentration (weighted) in imported tomatoes was 0.03 ppm(3).

cis-Permethrin Concentrations - FDA Total Diet Study Market Baskets (1991-93) (1).[Table#6279]

Permethrin food detections(1-4).[Table#6280]

Neurotoxin - Other CNS neurotoxin

Adverse effects reported during the treatment of scabies with permethrin include increased or new onset of pruritus, burning, or a stinging sensation. These dermatologic adverse events were mild in severity and temporary. There have also been reports of stinging when applying 1% permethrin for pediculosis capitis.

The substance can be absorbed into the body by inhalation of its aerosol and by ingestion.

Inhalation (L857) ; oral (L857) ; dermal (L857) ; eye contact (L857). Poorly absorbed through the skin.

Carcinogenesis, mutagenesis, and impairment of fertility: 6 carcinogenicity bioassays were evaluated with permethrin. No tumorigenicity has been observed in the rat studies. However, the 3 mouse studies saw an increase in pulmonary adenomas. In one of these studies, there was a raised incidence of pulmonary alveolar-cell carcinomas and benign liver adenomas in female mice. Permethrin exhibited no mutagenic potential in genetic toxicity studies (in vitro and in vivo). Permethrin did not adversely impact reproductive function when given orally at a 180 mg/kg/d dose in a 3-generation rat study.

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 Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including permethrin, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Tolerances are established for the combined residues of the insecticide cis- and trans-permethrin isomers [cis-(3-phenoxyphenyl)methyl 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane carboxylate] and [trans-(3-phenoxyphenyl)methyl 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane carboxylate] in/on the following food commodities:[Table#6277]

Tolerances with regional registration, as defined in section 180.1(l) are established for the combined residues of the insecticide cis- and trans-permethrin isomers [cis-(3-phenoxyphenyl)methyl 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane carboxylate] and [trans-(3-phenoxyphenyl)methyl 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane carboxylate] in/on the following food commodities:[Table#6278]

The Agency has completed its assessment of the dietary, occupational, residential, and ecological risk associated with the use of pesticide products containing the active ingredient permethrin. Based on a review of these data and on public comments on the Agency's assessments for the active ingredient permethrin, the Agency has sufficient information on the human health and ecological effects to make decisions as part of the tolerance reassessment process under FFDCA and reregistration process under FIFRA, as amended by FQPA. The Agency has determined that permethrin-containing products are eligible for reregistration provided that: (i) the risk mitigation measures outlined in this document are adopted and (ii) label amendments are made to reflect these measures. ... Based on its evaluation of permethrin, the Agency has determined that permethrin products, unless labeled and used as specified in this document, would present risks inconsistent with FIFRA. Accordingly, should a registrant fail to implement any of the risk mitigation measures identified in this document, the Agency may take regulatory action to address the risk concerns from the use of permethrin. If all changes outlined in this document are incorporated into the product labels, then all current risks for permethrin will be adequately mitigated for the purposes of this determination under FIFRA.

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their continued use. Under this pesticide reregistration program, EPA examines newer health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether the use of the pesticide does not pose unreasonable risk in accordance to newer saftey standards, such as those described in the Food Quality Protection Act of 1996. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA '88 were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern than those on List C, and with List C containing pesticides of greater concern than those on List D. Permethrin is found on List B. Case No: 2510; Pesticide type: Insecticide; Case Status: OPP is reviewing data from the pesticide's producers regarding its human health and/or environmental effects, or OPP is determining the pesticide's eligibility for reregistration and developing the Reregistration Eligibility Decision (RED) document.; Active ingredient (AI): 3-(Phenoxyphenyl)methyl (+-)cis,trans-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate; Data Call-in (DCI) Date(s): 08/09/91, 01/02/92, 04/11/94, 03/03/95, 10/13/95; AI Status: The producers of the pesticide has made commitments to conduct the studies and pay the fees required for reregistration, and are meeting those commitments in a timely manner.

P03AC04

P - Antiparasitic products, insecticides and repellents

QP - Antiparasitic products, insecticides and repellents

P03AC04

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.

Permethrin is pediculocidal by disrupting in sodium channel current in the louse's nerve cell membrane; this action causes delayed polarization of the membrane and paralysis of the insect.

Like natural pyrethrins, permethrin acts as a neurotoxin by depolarizing nerve cell membranes of parasites. The drug disrupts the sodium channel current by which membrane repolarization is regulated. Delayed repolarization results in paralysis of the nerves in the exoskeletal respiratory muscles of the parasite leading to death.

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/

Trans- and cis-permethrin were irradiated in sunlight and at gamma>290 nm in hexane, methanol, water and water acetone. Isomerization and ester cleavage occurred primarily. Observed products included monochloropermethrin and the monochlorovinyl acid from cleavage, 3-phenoxybenzyl 3,3-dimethylacrylate, 3-phenoxybenzaldehyde, 3-phenoxybenzoic acid, benzyl alcohol, benzaldehyde, 3-hydroxybenzyl alcohol, benzoic acid, 3-hydroxybenzoic acid, and 3-phenoxybenzyl alcohol.

For more Mechanism of Action (Complete) data for PERMETHRIN (10 total), please visit the HSDB record page.

The toxicokinetics of permethrin after single 460 mg/kg oral and 46 mg/kg intravenous doses were studied in male Sprague-Dawley rats. Serial blood samples after oral and intravenous dosage, and brain, medulla oblongata, sciatic nerve, and liver samples after oral administration were collected. Plasma, hypothalamus, cerebellum, frontal cortex, caudate putamen, hippocampus, medulla oblongata, sciatic nerve, and liver concentrations of permethrin and its metabolites, m-phenoxybenzyl alcohol and m-phenoxybenzoic acid, were determined by a high-performance liquid chromatographic assay. The permethrin plasma profile could be adequately described by a two-compartment open model. For permethrin, the elimination half-life (t1/2 beta) and the mean residence time from plasma were 8.67 and 11.19 hr after i.v. and 12.37 and 17.77 hr after /peroal/ administration. The total plasma clearance was not influenced by dose concentration or route and reached a value of 0.058 liter/hr. After the single oral dose, permethrin was absorbed slowly with a Tmax of 3.52 hr. The maximum plasma concentration was 49.46 micrograms/ml. The oral bioavailability of permethrin was found to be 60.69%. The plasma concentration-time data for permethrin metabolites as well as the tissue concentration-time data for permethrin and its metabolites after an oral dose of permethrin were found to fit a one-compartment open model. The elimination half-life (t1/2el) of permethrin was greater for the hippocampus, medulla oblongata, frontal cortex, and sciatic nerve (23.10, 22.36, 13.86, and 16.27 hr, respectively) than for plasma (t1/2 beta, 12.37 hr). The maximum amounts of permethrin in cerebellum, hippocampus, caudate putamen, frontal cortex, hypothalamus, and sciatic nerve were about 1.5, 2, 2, 2.7, 4.8, and 7.5 times higher than in plasma, respectively, indicating an accumulation of pyrethroid by nervous tissue itself. Nervous tissue accumulation of permethrin was also reflected by the area under the concentration curve ratios of tissue/plasma (1.16, 3.71, 1.57, 4.27, 3.48, and 8.77, respectively). The metabolites of permethrin, m-phenoxy-benzyl alcohol and m-phenoxybenzoic acid, were detected in plasma and in all selected tissues for 48 hr after dosing, suggesting that a combination of metabolism by the tissues and diffusion into it from the blood may be present.

In studies, the half-life of (+)-trans- and (+)-cis-permethrin applied to the leaf surface of bean plants was 7 and 9 days, respectively.

Rapidly metabolized by ester hydrolysis to inactive metabolites which are excreted primarily in the urine.

When the four (14)C-preparations of (IRS)-trans-, (IR)-trans- , (IRS)-cis, and (IR)-cis-permethrin labeled in the alcohol and acid moieties were administered orally to male rats at 1.6-4.8 mg/kg, the compounds were rapidly metabolized and the (14)C from the acid and alcohol moeity was almost completely eliminated from the body within a few days. ... The major metabolic reactions of both permethrin isomers /(trans and cis)/ were oxidation at the trans and cis portions of the gem-dimethyl group of the acid moiety and at the 2'- and 4'-positions of the alcohol moiety, ester cleavage, and the conjugation of the resulting carboxylic acids, alcohols, and phenols with glucuronic acid, glycine, and sulfuric acid. The cis isomer is more stable than the tans isomer, and the cis isomer yielded four fecal ester metabolites which resulted from hydroxylation at the 2'- and 4'-positions of the phenoxy group, at the trans- methyl group, and at both of the two latter sites. The ester-cleaved metabolites were extensively excreted into the urine, whereas the metablites retaining ester linkage were found only in the feces. There were no significant differences in metabolism between the (IRS)-isomers and (IR)-isomers.

When White Leghorn hens were treated orally three consecutive days with one of four (14)C-trans- and cis-permethrin isomers labelled in the alcohol or acid at 10 mg/kg body weight, they showed no signs of poisoning. More than 87% of the radiocarbon from the four labelled perparations was found in the excreta 9 days after the initial dose, 0.7-4.7% of the dose was exhaled as (14)CO2, and 0.12-0.47% and 0.06-0.66% of the radiocarbon was recovered in egg yolk and fat (subcutaneous and visceral fat), respectively. Both the cis isomers labelled in the alcohol and acid moieties showed recoveries 3 to >10 times higher in the fat and egg yolk than those shown by the corresponding trans isomers. The excreta (0-72 hr) contained 1.7 times more cis-permethrin than trans-permethrin. Hydroxylated ester metabolites of trans-permethrin were not excreted, but four monohydroxy and dihydroxy esters (i.e. trans-OH-permethrin, 4'-OH-permethrin, 4'-OH, trans-OH-permethrin and trans-OH-permethrin sulfate) of cis-permethrin were found. Metabolites from the acid moieties of both isomers were the Cl2CA isomers in free, glucuronide, and taurine conjugate forms, trans-OH-Cl2CA, cis-OH-Cl2CA, cis-OH-Cl2CA lactone, and cis-OH-Cl2CA sulfate. trans-OH-Cl2CA was obtained from the cis isomer to larger extents than from the trans isomer, whereas the amounts of cis-OH-Cl2-CA were larger with the trans isomer than with the cis isomer. The metabolites from the alcohol moiety included PBalc, PBacid, their 4'-hydroxy-derivatives and the corresponding sulfate the glucuronide of PBalc, and a variety of unidentified conjugates of 4'-OH-PBalc and 4'-OH-PBacid. The taurine conjugate of PBacid was not detected. The metabolites produced in largest amounts were the unidentified conjugates of 4'-OH-PBalc (6-13% of the dose) and 4'-OH-PBacid (2-11%). The yolk of eggs 5 and 6 days after initial dosing contained 4.4 times cis-perethrin than trans-permethrin in unchanged form and the same ester metabolites of cis-permethrin as those found in the excreta. Other metabolites in the yolk were generally the same as those in the excreta. Overall, cis-permethrin appeared at higher levels than trans-permethrin in the egg yolk, fatty tissues, and excreta. Radiocarbon from cis-permethrin preparations also persisted longer in the blood than that from trans-permethrin preparations. It probably resulted from more rapid ester cleavage of the trans isomer than the cis isomer, based on the relative amounts of hydrolysis products form the two isomers in hen excreta.

Two human volunteers, who consumed about 2 and 4 mg of permethrin (25:75), respectively, excreted 18-37% and 32-39% of the administered dose, detected as the metabolite Cl2CA, after acid hydrolysis of their urine collected over 24 hr.

The permethrin metabolites in goats were formed through cleavage of the ester linkage, hydroxylation at the cis- or trans-methyl of the geminal dimethyl group, and hydroxylation at the 4'-position of the phenoxybenzyl moiety. Some of these metabolic products were further oxidized and/or conjugated with glycine, glutamic acid and glucuronic acid. The major compounds found in feces after dosing with cis-permethrin were unmetabolized parent compound 4'-OH-permethrin, trans-OH-permethrin, PBalc, cis-OH-cis-Cl2CA-lactone and eight unidentified ester metabolites. The feces of goats treated with the trans isomer contained large amounts of the parent compound (41-79% of the fecal (14)C and of PBalc (8-25%) and cis-OH-trans-Cl2CA-lactone. Also, three unidentified ester metabolites were found (8-23%). On the other hand, major urinary metabolites from the alcohol moiety of both isomers were PBacid-glycine (7-9% of the urinary (14)C) and r'-OH-PBacid-glycine (4-12%). PBalc, PBacid, 4'-OH-PBalc, 4'-OH-PBacid, PBacid-glutamic acid and 4'-OH-PBacid-glutamic acid were also identified as minor metabolites. The urine of goats treated with both isomers contained as major components, Cl2CA in the free form (2-4% of the urinary (14)C) and as a glucuronide (27-71%). Cl2CA-glucuronide was obtained to a larger extent with the trans isomer than with the cis isomer. Other major metabolites of the cis isomer were cis-OH-Cl2CA (33) (9-11%) and cis-OH-cis-Cl2CA-lactone (11-16%). trans-OH-Cl2CA was detected as a minor metabolite of both isomers. The milk of goats contained the parent compounds, PBacid-glycine, and 4'-OH-PBacide-glycine. On administration of the cis isomer, a large amount of the parent compund was excreted in the milk than in the case of the trans isomer. Comparatively, when the trans isomer was administered, PBacid-glycine was detected in the milk to a larger extent than with the cis isomer. Most of the radioactivity in the fat was attributed to the parent compound or ester metabolites such as trans-OH-permethrin and trans-OH-permethrin conjugate.

For more Metabolism/Metabolites (Complete) data for PERMETHRIN (25 total), please visit the HSDB record page.

509F88P9SZ

PERMETHRIN

Chemical Structure [CS] - Pyrethrins

Established Pharmacologic Class [EPC] - Pyrethroid

Permethrin is a Pyrethroid.

AIRLINE PESTICIDE DETOX

Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.

Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics.

Poorly absorbed through the skin.

Permethrin is rapidly metabolized by ester hydrolysis to inactive metabolites which are excreted primarily in the urine.

Lactating cows (three/group) fed permethrin at dose levels of 0, 0.2, 1.0, 10, 50 mg/kg diet for 28 days showed no mortality, and growth and milk production were normal. Permethrin residues were observed in the milk within 3 days at the two highest dietary levels; levels appeared to reach a plateau rapidly and not to increase with time. Analysis of individual cis and trans isomers showed that the ratio of permethrin isomers in milk appeared to change during the course of the study with the cis isomer predominating. Permethrin residues were not found in the tissues of animals that received doses of 1 mg/kg or less. At dose levels of 10 or 50 mg/kg, residues were detected in the tissues, predominantly in the fat. Low levels were also present in the muscle and kidney at the highest dose level. Permethrin did not appear to accumulate in the fat but to reach a plateau rapidly.

(14)C-cis-Permethrin was applied to the clipped skin of mice at a level of 1 mg/kg body weight in 0.1 mL of acetone. The mice were restrained until the solvent had evaporated and then placed in mouse metabolism cages. They were sacrificed at 1, 5, 15, 50, 480, and 2880 min after treatment and examined for absorption, distribution, and excretion of the insecticide. About 40% of the applied permethrin had moved from the site of application within 5 min and appeared to move rapidly to other parts of the body.

When ten consecutive oral doses of (14)C-trans- or (14)C-cis- permethrin (labelled in the acid or alcohol moieties) at 0.2-0.3 mg/kg bw/day were given to lactating goats, they excreted 72-79% and 25-36% of the trans and cis isomer doses, respectively, in urine & 12-15%, respectively, in the feces. The amounts of the radiocarbon appearing in the milk were <0.7% with any one of the four (14)C-labelled preparations. Concerning the tissue residues 24 hr after the last dose, detectable levels of radiocarbon were found in most tissue, but none was >0.04 mg/kg for the trans isomer or 0.25 mg/kg for the cis isomer.

Two human volunteers, who consumed about 2 and 4 mg of permethrin (25:75), respectively, excreted 18-37% and 32-39% of the administered dose, detected as the metabolite Cl2CA, after acid hydrolysis of their urine collected over 24 hr.

Used as an ectoparasiticide in humans and animals; [Merck Index] Used as a nematocide, acaricide, and insecticide; [Hawley]

Farming (Pesticides) [Category: Industry]

For permethrin (USEPA/OPP Pesticide Code: 109701) ACTIVE products with label matches. /SRP: Registered for use in the U.S. but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./

The pyrethroids are the most widely used class of insecticides in wood preservation because of their broad-spectrum activity, high efficacy especially against wood boring beetle, and high resistance to leaching. /Synthetic pyrethroids/

Insecticide, seed treatment/protectant.

It has a potential application for forest protection and vector control for the control of noxious insects in the household and on cattle, for the control of body lice, and in mosquito nets.

Permethrin can be produced by condensation of 3-phenoxybenzyl alcohol with (1RS)-cis/trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid.

The starting acid is prepared by a variation of the conventional chrysanthemic acid synthesis using ethyldiazoacetate in which 1,1-dichloro-4-methyl-1,3-pentadiene is reacted with ethyldiazoacetate in the presence of a copper catalyst and the resulting ethyl (+,-)- cis,trans-2,2-dimethyl-3-(2,2-dichlorovinyl)cyclopropanecarboxylate hydrolysed to the free acid. The cis- and trans-isomers can be separated from one another by selective crystallization from n-hexane in which the cis-isomer is more soluble. The starting acid is then reacted with 3-phenoxybenzyl alcohol to give permethrin.

Preparation of the racemic mixture: T. Mizutani et al, German patent 2437882 (1975 to Sumitomo); F. Mori et al; German patent 2544150; eidem, United States of America patent 4113968 (1976, 1978, both to Kuraray).

Dust, emulsifiable concentrate, smokes, ULV /ultra low volume/, wettable powder.

Premix Partners: carboxin; dichlofluanid; piperonyl butoxide; tebuconazole; tetramethrin.

Technical material is a mixture of ~60% trans- and 40% cis-isomers.

Permethrin is typically a mixture of (+) cis and (+) trans esters ... in either a 40:60 or 25:75 ratio.

For more Formulations/Preparations (Complete) data for PERMETHRIN (46 total), please visit the HSDB record page.

Cosmetics product ingredient: Permethrin (including cis- and trans-)

Information on 256 consumer products that contain Permethrin in the following categories is provided:

Veterinary Drug -> INSECTICIDE -> JECFA Functional Classes

INSECTICIDES

The WHO Recommended Classification of Pesticides by Hazard identifies permethrin (technical grade) as Class II: moderately hazardous; Main Use: insecticide.

Synthetic pyrethroid insecticide. ... Of the four possible isomers, the (1R,trans)- and the (1R,cis)-isomers are the two esters primarily responsible for insecticidal activity.

Permethrin was first registered and tolerances established in the United States in 1979 for use on cotton (April 29, 1979 44FR 24287). The registration was made conditional due to the need for additional toxicology data to fully evaluate carcinogenicity and the need for additional ecological effects data to fully evaluate aquatic risk. Laboratory studies indicated that permethrin was highly toxic to fish and aquatic invertebrates and the use on cotton was classified as Restricted Use pesticide (RUP). In making its decision to conditionally register the product, EPA considered the beneficial role of this compound in cotton pest management, the reduction of use of other cotton insecticides with known carcinogenic potentials, and the absence of suitable and sufficient supplies of alternatives for control of resistant insect strains.

Permethrin is a restricted use pesticide for crop and wide area applications (i.e. nurseries, sod farms) due to high toxicity to aquatic organisms. It is a general use pesticide for residential and industrial applications.

For more General Manufacturing Information (Complete) data for PERMETHRIN (7 total), please visit the HSDB record page.