PERMETHRIN
Human Health Effects:
Evidence for Carcinogenicity:
Evaluation: No data were available from studies in humans. There is inadequate evidence
for the carcinogenicity of permethrin in
experimental animals. Overall evaluation: Permethrin
is not classifiable as to its carcinogenicity to humans (Group 3).
Human Toxicity Excerpts:
To assess the human tolerance, absorption, and persistence of permethrin
when used against human lice, 10 adult volunteers (four men, six women) were treated with
15-40 ml of permethrin (25:75) (1%) head louse
solution. Their hair was allowed to dry naturally and then washed with baby shampoo. Urine
samples were collected at 0-24, 24-48, 120-144, and 336-360 hr to measure dermal
absorption. On assessment, 3 out of 10 volunteers developed mild, patchy erythema, which
faded between days 4-7. Permethrin excretion
during the first 24 hr was only about 1% of the applied dose, while the cumulative maximum
over 14 days was only about 5.5 mg.
In a study to assess the degree the dermal absorption of permethrin
from impregnated clothing, a group of 10 male volunteer soldiers for 48 hr wore military
clothing that had previously been treated with an aqueous suspension of permethrin
(0.2% w/v). Subsequent analysis showed that the mean permethrin
(25:75) concn of the shirts & trousers was 0.32 g/100 g. However, the average
individual exposure to permethrin was 3.8
mg/day. No volunteers complained of irritation & there were no abnormal findings on
physical examination.
The difference in the degree of paraesthesia induced by a number of pyrethroids /was
studied/. On five occasions, 0.05 ml of field-strength-formulated permethrin
(0.13 mg/cu m) was applied to a 4 cu cm area of earlobe. The opposite earlobe received
distilled water. Participant evaluation after each application continued for 48 hr and
involved description of the cutaneous sensations. Each participant was treated after each
application with one of the remaining compounds. Permethrin,
like the other pyrethroids, induced skin sensations. Paraesthesia developed with a latency
period of approximately 30 min, peaked by 8 hr, and deteriorated within 24 hr. In the case
of permethrin these sensations were
approximately four times less marked than those induced by cypermethrin and fenvalerate,
which both contain an alpha-cyano-group. It was also found that local application of
di-alpha-tocopheryl acetate markedly inhibited the occurrence of skin sensations.
Studies of occupational exposure to permethrin
were reported in Sweden. In the first study, six forestry workers using an aqueous
emulsion of permethrin (trans:cis=75:25) were
studied. The duties of these workers involved dipping conifer seedlings in a 2% aqueous
emulsion of permethrin (one worker) &
packaging the permethrin-treated seedlings (five
workers). The permethrin concn in the breathing
zones of these workers varied between 0.011 & 0.085 mg/cu m. One person excreted permethrin metabolites at 0.26 ug/ml urine the
following morning, but the same afternoon the urinary excretion of permethrin
residues was below the detection limit of 0.1 ug/ml. The urine from other workers did not
contain detectable amounts of permethrin
residues. No symptoms of permethrin poisoning
were reported in this field study. The second study performed on the basis of a
questionnaire & interviews, was conducted 1-2 months after the planting season. It
involved 87 persons at various plant nurseries that used the insecticide (trans:cis-60:40
or 75/25). This study showed that the major work related symptoms amongst workers were
irritative, such as itching & burning of the skin, & itching & irritation of
the eyes. Irritative symptoms in the skin & upper respiratory tract were reported in
63% of workers who were exposed to permethrin
(trans:cis=75:25) & 33% who were exposed to permethrin
with a different isomer composition (trans:cis=60:40). The frequency of each symptom was
about 10% in each case. Incr nasal secretion was reported by 13% of the workers handling permethrin (trans:cis=75:25).
23 Laboratory workers involved in field trials, formulation, or general laboratory work
with permethrin, cypermethrin, fenvalerate,
& fenpropathrin /were examined/. The study involved electrophysiological monitoring
& interviews to ascertain subjective symptoms. The most frequently reported symptom
was facial sensation described as tingling, burning, or nettle rash by workers who had
experienced it on one or more occasions. This sensation ususally occurred about 30 min to
3 hr after exposure & lasted for about 30 min to 8 hr. Apparently this did not occur
when permethrin alone was involved. All the
workers were examined neurologically & no abnormal findings were recorded.
Electrophysiological measurements from these workers were compared with those of an
age-matched control group. No difference in response was found between the two groups.
When dermally exposed to permethrin (25:75)
1% w/w in soft paraffin for up to 9 days using a patch test, 2 out of 17 volunteers
developed mild erythema.
A 25% water-wettable powder formulation of permethrin
was applied as an indoor residual spray at a target dosage of 0.5 g/sq m. One bagger, one
mixer, and three spraymen treated a village in 2 days. Each man wore overalls (washed
daily) shoes, and a hat. The mixer wore a cartridge-type respirator and rubber gloves. The
bagger wore the same plus an apron. The spraymen did not wear masks. All practiced good
personal hygiene. The men were examined before and 1 day after exposure. No complaints
were received, and no abnormalities were detected. Protective clothing of the spraymen was
the same, and the man who absorbed more had sprayed only slightly more.
Mild, limited pruritus occurs in about 6% of patients. The pruritus, erythema, &
edema that normally accompany head lice infestation may be exacerbated temporarily.
Transient burning, stinging, tingling, numbness, or scalp discomfort occurs in approx 3.4%
of patients, & 2.1% experience mild transient erythema, edema, or rash of the scalp.
The potential for contact dermatitis and photosensitization is very low.
An observational, epidemiological study was undertaken to evaluate the safety of permethrin 1% creme rinse (Nix) for treatment of head
lice infestations. 37 local public health departments enrolled a total of 38,160 patients
for 47,578 treatments with permethrin or other
pediculicides from September 1, 1986, through January 31, 1988. Follow-up safety
information was collected between 7 & 14 days following treatment via return visit or
telephone contact. 103 adverse events were reported among 41,955 evaluable treatments. The
rates of reported adverse events were 2.2 per 1000 treatments among permethrin
treatments, 3.4 per 1000 treatments among lindane treatments, & 1.5 per 1000
treatments among other over the counter treatments. No serious, unexpected adverse events
were detected in the 18,950 patients treated with permethrin.
This study confirmed the safety profile of permethrin
in conditions of general use, as seen in clinical trials. Postmarketing safety monitoring
in public health departments of drugs used to treat public health conditions was shown to
be feasible.
Synthetic pyrethroids are neither cutaneous sensitizers nor irritants. Although these
compounds do not cause signs of inflammation (edema, erythema, vesiculation), they do
produce paresthesias after contact. Typically, symptoms begin several hours after
cutaneous exposure, peak in the evening, and resolve by the following day. /Synthetic
pyrethroids/
One of 28 subjects with pediculosis pubis treated with 1% permethrin
rinse developed mild scrotal erythema and irritation 12 hours after application.
The allergenic properties of pyrethroids /with early pyrethrum preparations/ are marked
in comparison with other pesticides. Many cases of contact dermatitis and respiratory
allergy have been reported. Persons sensitive to ragweed pollen are particularly prone to
such reactions. Preparations containing synthetic pyrethroids are less likely to cause
allergic reactions than are the preparations made from pyrethrum powder. /Pyrethroids/
Some pyrethroid (eg, deltamethrin, fenvalerate, cyhalothrin, lambda-cyhalothrin,
flucythrinate, & cypermethrin) may cause a transient itching &/or burning
sensation in exposed human skin. /Synthetic pyrethroids/
Synthetic pyrethroids are neuropoisons acting on the axons in the peripheral & CNS
by interacting with sodium channels in mammals &/or insects. A single dose produces
toxic signs in mammals, such as tremors, hyperexcitability, salivation, choreoathetosis,
& paralysis. ... At near-lethal dose levels, synthetic pyrethroids cause transient
changes in the nervous system, such as axonal swelling &/or breaks & myelin
degeneration in sciatic nerves. They are not considered to cause delayed neurotoxicity of
the kind induced by some organophosphorus compounds. /Synthetic prethroids/
The clinical manifestations of inhalation exposure to pyrethrins can be local or
systemic. Localized reactors confined to the upper respiratory tract include rhinitis,
sneezing, scratchy throat, oral mucosal edema, & even laryngeal mucosal edema.
Localized reaction of the lower respiratory tract include cough, shortness of breath,
wheezing, & chest pain. An asthmalike reaction occurs with acute exposures in
sensitized patients. Hypersensitivity pneumonitis characterized by chest pain, cough,
dyspnea, & bronchospasm may occur in an individual chronically exposed. /Pyrethrum and
synthetic pyrethroids/
The low toxicity of pyrethroids in mammals is due largely to their rapid
biotransformation by ester hydrolysis and/or hydroxylation. /Pyrethroids/
Skin, Eye and Respiratory Irritations:
Mild irritant to skin and eyes. /Technical permethrin/
Immediately irritating to the eye. /Pyrethrins/
The chief effect from exposure ... is skin rash particularly on moist areas of the
skin. ... May irritate the eyes. /Pyrethroids/
Drug Warnings:
The safety and effectiveness of permethrin in
children less than 2 years of age have not been established.
Patients who cannot tolerate chrysanthemums, pyrethrins, and other synthetic
pyrethroids may not tolerate permethrin.
Medical Surveillance:
Initial medical screening: Employees should be screened for history of certain medical
conditions ... which might place the employee at increased risk from /pyrethroid/
exposure. Chronic respiratory disease: In persons with chronic respiratory disease,
especially asthma, the inhalation of /pyrethroids/ might cause exacerbation of symptoms
due to its sensitizing properities. Skin disease: /Pyrethroids/ can cause dermatitis which
may be allergic in nature. Persons with pre-existing skin disorders may be more
susceptible to the effects of this agent. Any employee developing the above-listed
conditions should be referred for further medical examination. /Pyrethrum/
Probable Routes of Human Exposure:
Occupational exposure to permethrin may occur
through inhalation and dermal contact with this compound at workplaces where permethrin is produced or used(SRC). Monitoring data
indicate that the general population may be exposed to permethrin
via inhalation of ambient air and ingestion of food, and with the household use of
insecticides containing permethrin(SRC). In
Japan, the concn of permethrin in the air near a
spreader's mouth area was 14.6 ug/cu m during application of the pesticide(1).
Permethrin is applied to several crops via
aerial or ground spraying(1). In pesticide formulating plants, exposure to permethrin may be from spillage; furthermore, there is
a high potential for exposure at mixing and bagging stations(2). Crop workers may be
exposed during application; however, their main exposure results from contact with treated
foliage or to pesticide or pesticide-contaminated material made airborn through agitation
of foliage during work activity(2). Incidental to treating a crop, some pesticides, such
as permethrin, may drift onto workers in
neighboring fields or in nearby suburban areas without there being any intent to treat
those areas(2). Therefore exposure of the general population to permethrin
may occur through inhalation and dermal contact resulting from spraying nearby areas(2).
According to a pilot investigation of pesticides in 9 homes in Jacksonville, FL during
August of 1985, potential respiratory exposure to permethrin
was estimated in 1 home using a personal monitor carried by a resident of each
household(1).
Body Burden:
The concn 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 a 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).
Average Daily Intake:
The average daily intake (AVDI) of permethrin
in 8 population groups in 1982-1984 was determined according to the FDA's monitoring
program for chemical contaminants in the U.S. food supply (Total Diet Study or Market
Basket Study). In 6-11 month old infants, the AVDI was 1.2 ng/kg-body weight-per day. In 2
yr old toddlers, the AVDI was 5.6 ng/kg-body weight-per day. In 14-16 year old females,
the AVDI was 3.3 ng/kg-body weight-per day. In 14-16 year old males, the AVDI was 3.0
ng/kg-body weight-per day. In 25-30 year old females, the AVDI was 5.0 ng/kg-body
weight-per day. In 25-30 year old males, the AVDI was 4.1 ng/kg-body weight-per day. In
60-65 year old females, the AVDI was 6.5 ng/kg-body weight-per day. In 60-65 year old
males, the AVDI was 5.4 ng/kg-body weight-per day(1).
The average daily intake (AVDI) of permethrin
(total) in 8 population groups in 1986-1991 was determined according to the FDA's
monitoring program for chemical contaminants in the U.S. food supply (Total Diet Study or
Market Basket Study). In 6-11 month old infants, the AVDI was 4.7 ng/kg-body weight-per
day. In 2 yr old toddlers, the AVDI was 7.1 ng/kg-body weight-per day. In 14-16 year old
females, the AVDI was 3.6 ng/kg-body weight-per day. In 14-16 year old males, the AVDI was
4.2 ng/kg-body weight-per day. In 25-30 year old females, the AVDI was 5.7 ng/kg-body
weight-per day. In 25-30 year old males, the AVDI was 4.6 ng/kg-body weight-per day. In
60-65 year old females, the AVDI was 5.9 ng/kg-body weight-per day. In 60-65 year old
males, the AVDI was 5.9 ng/kg-body weight-per day(1).
The average daily intake (AVDI) of permethrin
(total) in 8 population groups in 1984-1996 was determined according to the FDA's
monitoring program for chemical contaminants in the U.S. food supply (Total Diet Study or
Market Basket Study). In 6-11 month old infants, the AVDI was 44.1 ng/kg-body weight-per
day. In 2 yr old toddlers, the AVDI was 12.8 ng/kg-body weight-per day. In 14-16 year old
females, the AVDI was 5.5 ng/kg-body weight-per day. In 14-16 year old males, the AVDI was
7.6 ng/kg-body weight-per day. In 25-30 year old females, the AVDI was 7.7 ng/kg-body
weight-per day. In 25-30 year old males, the AVDI was 7.0 ng/kg-body weight-per day. In
60-65 year old females, the AVDI was 12.4 ng/kg-body weight-per day. In 60-65 year old
males, the AVDI was 11.5 ng/kg-body weight-per day(1).
Emergency Medical Treatment:
Emergency Medical Treatment:
| EMT Copyright Disclaimer: |
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reference. THE COMPLETE POISINDEX(R) DATABASE, AVAILABLE FROM MICROMEDEX, SHOULD BE
CONSULTED FOR ASSISTANCE IN THE DIAGNOSIS OR TREATMENT OF SPECIFIC CASES. Copyright
1974-1998 Micromedex, Inc. Denver, Colorado. All Rights Reserved. Any duplication,
replication or redistribution of all or part of the POISINDEX(R) database is a violation
of Micromedex' copyrights and is strictly prohibited. The following Overview, *** PYRETHRINS ***, is relevant for this HSDB record chemical. |
| Life Support: |
o This overview assumes that basic life support measures
have been instituted.
|
| Clinical Effects: |
SUMMARY OF EXPOSURE
0.2.1.1 ACUTE EXPOSURE
o The mammalian toxicity of natural pyrethrins is
generally low. Very young children are perhaps more
susceptible to poisoning because they may not hydrolyze
the pyrethrum esters efficiently. In humans, allergic
reactions are the main toxic manifestations of
pyrethrin exposure.
1. Pyrethrum and the pyrethrins produce typical type I
motor symptoms in mammals. Severe type I poisoning
may include the following signs in humans:
Severe fine tremor
Marked reflex hyperexcitability
Sympathetic activation
Paresthesia (dermal exposure)
o DERMAL - These compounds are not primary irritants.
The chief effect, however, from exposure is dermatitis.
The usual lesion is a mild erythematous dermatitis with
vesicles, papules in moist areas, and intense pruritus;
a bulbous dermatitis may also occur. Pyrethrins can
cause allergic dermatitis and systemic allergic
reactions.
o INHALATION is the major route of exposure, with airway
irritation as the primary toxic effect. Following
inhalation, a stuffy, runny nose and scratchy throat
are common. Hypersensitivity reactions including
wheezing, sneezing, shortness of breath and
bronchospasm may be noted.
o OCULAR - Eye exposures may result in mild to severe
corneal damage that generally resolves with
conservative care.
o Piperonyl butoxide and other compounds are often added
to pyrethrin insecticides as synergists and may
contribute to toxicity.
o Synthetic pyrethroids, which are related to pyrethrins,
are covered in a separate management.
HEENT
0.2.4.1 ACUTE EXPOSURE
o A stuffy, runny nose and scratchy throat following
inhalational exposure may be noted.
o Eye exposures may result in mild to severe corneal
damage, decreased visual acuity and periorbital edema.
CARDIOVASCULAR
0.2.5.1 ACUTE EXPOSURE
o Hypotension and tachycardia, associated with
anaphylaxis, may occur.
RESPIRATORY
0.2.6.1 ACUTE EXPOSURE
o Hypersensitivity reactions characterized by
pneumonitis, cough, dyspnea, wheezing, chest pain, and
bronchospasm may occur. Rare cases of respiratory
failure and cardiopulmonary arrest have been reported.
NEUROLOGIC
0.2.7.1 ACUTE EXPOSURE
o Paresthesias, headaches, and dizziness are common.
Massive exposure may result in hyperexcitability and
seizures, but this is rare.
GASTROINTESTINAL
0.2.8.1 ACUTE EXPOSURE
o Nausea, vomiting and abdominal pain commonly occur and
develop within 10 to 60 minutes following ingestion.
DERMATOLOGIC
0.2.14.1 ACUTE EXPOSURE
o Irritant and contact dermatitis may develop. Erythema
which mimics sunburn has also been noted after
prolonged repeated exposure.
ENDOCRINE
0.2.16.1 ACUTE EXPOSURE
o Type I motor symptoms following severe poisoning may
result in sympathetic activation.
IMMUNOLOGIC
0.2.19.1 ACUTE EXPOSURE
o Sudden bronchospasm, swelling of oral and laryngeal
mucous membranes, and anaphylactoid reactions have been
reported after pyrethrum inhalation. Hypersensitivity
pneumonitis characterized by cough, shortness of
breath, chest pain, and bronchospasm may be noted.
GENOTOXICITY
o Pyrethrum is not mutagenic in bacterial reversion tests
(Ray, 1991).
|
| Laboratory: |
o Pyrethrin plasma levels are not clinically useful or
readily available.
o Monitor for allergic responses such as asthma or contact
dermatitis.
|
| Treatment Overview: |
ORAL EXPOSURE
o There is no specific antidote for pyrethrin poisoning.
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.
o ALLERGIC REACTION: MILD: antihistamines with or
without epinephrine. SEVERE: oxygen, aggressive
airway management, antihistamines, epinephrine (ADULT:
0.3 to 0.5 mL of a 1:1000 solution subcutaneously;
CHILD: 0.01 mL/kg; may repeat in 20 to 30 min),
corticosteroids, ECG monitoring, and IV fluids.
INHALATION EXPOSURE
o INHALATION: 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
beta2 agonist and corticosteroid aerosols.
EYE EXPOSURE
o DECONTAMINATION: Irrigate exposed eyes with copious
amounts of tepid water for at least 15 minutes. If
irritation, pain, swelling, lacrimation, or photophobia
persist, the patient should be seen in a health care
facility.
DERMAL EXPOSURE
o DECONTAMINATION: 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.
o Vitamin E topical application is highly effective in
relieving paresthesias.
|
| Range of Toxicity: |
o The minimal lethal dose of pyrethrum is not established,
but is probably in the range of 10 to 100 grams.
o Hypersensitivity reactions may be noted, especially
following a chronic dermal or inhalation exposure.
Patients with underlying asthma may be predisposed to
severe bronchospastic reactions after exposure.
|
Antidote and Emergency Treatment:
Treatment is supportive, and most casual exposures require only decontamination.
Topical vitamin E may ameliorate the paresthesias that accompany contact with synthetic
pyrethroids containing an alpha-cyano group (e.g., fenvalerate, cypermethrin,
flucythrinate). /Synthetic pyrethroids/
The additives (e.g. petroleum distillate), when present, represent a greater toxic
threat to the patient than the active ingredient itself. ... Emesis should not be induced
when petroleum distillate additives are present. ... The alert person with an intact gag
reflex & a sublethal pyrethrum ingestion without other toxic constituents may have
emesis induced by ipecac, followed by a saline cathartic & slurry of activated
charcoal. ... Pulmonary & allergic sequelae are treated symptomatically with airway
maintenance, oxygen, & ventilatory assistance as required. Standard drugs and
management protocols may be used for treatment of bronchospasm & anaphylaxis. Seizures
are treated with diazepam. /Pyrethrum and synthetic pyrethroids/
Skin decontamination. Wash skin promptly with soap and water ... . If irritant or
paresthetic effects occur, obtain treatment by a physician. Because volatilization of
pyrethroids apparently accounts for paresthesia affecting the face, strenuous measures
should be taken (ventilation, protective face mask and hood) to avoid vapor contact with
the face and eyes. Vitamin E oil preparations (dL-alpha tocopheryl acetate) are uniquely
effective in preventing and stopping the paresthetic reaction. They are safe for
application to the skin under field conditions. Corn oil is somewhat effective, but
possible side effects with continuing use make it less suitable. Vaseline is less
effective than corn oil. Zinc oxide actually worsens the reaction. /Pyrethroids/
Eye contamination. Some pyrethroid compounds can be very corrosive to the eyes.
Extraordinary measures should be taken to avoid eye contamination. the eye should be
treated immediately by prolonged flushing of the eye with copious amounts of clean water
or saline. If irritation persists, obtain professional ophthalmologic care. /Pyrethroids/
Gastrointestinal decontamination. If large amounts of pyrethroids, especially the
cyano-pyrethroids, have been ingested and the patient is seen soon after exposure,
consider gastrointestinal decontamination ... . Based on observations in laboratory
animals and humans, large ingestions of allethrin, cismethrin, fluvalinate, fenvalerate,
or deltamethrin would be the most likely to generate neurotoxic manifestations. If only
small amounts of pyrethroid have been ingested, or if treatment has been delayed, oral
administration of activated charcoal and cathartic probably represents optimal management.
Do not give cathartic if patient has diarrhea or on ileus. /Pyrethroids/
Other treatments. Several drugs are effective in relieving the pyrethroid neurotoxic
manifestations observed in deliberately poisoned laboratory animals, but none has been
tested in human poisonings. Therefore, neither efficacy nor safety under these
circumstances is known. Furthermore, moderate neurotoxic symptoms and signs are likely to
resolve spontaneously if they do occur. /Pyrethroids/
Animal Toxicity Studies:
Evidence for Carcinogenicity:
Evaluation: No data were available from studies in humans. There is inadequate evidence
for the carcinogenicity of permethrin in
experimental animals. Overall evaluation: Permethrin
is not classifiable as to its carcinogenicity to humans (Group 3).
Non-Human Toxicity Excerpts:
Long-term studies with rats and mice fed diets containing up to 2500 ppm (mg/kg) permethrin (40:60 cis:trans) indicated effects on the
central nervous system, such as tremors and hypersensitivity to noise, in rats only and
only during and first two weeks. Liver hypertrophy, increased microsomal enzyme activity
and proliferation of smooth endoplasmic reticulum occurred in both species but was less
pronounced in mice.
Non-phytotoxic when used as directed (except that some ornamentals may be injured)
Rats fed 3000 ppm permethrin in their diet
for 6 months showed typical motor symptoms in the early stages of the study but no other
changes except for a slight incr in liver weight assoc with an incr in smooth endoplasmic
reticulum. Rats fed 5000 ppm or more for 14 days developed acute poisoning & deaths
occurred. Animals showing severe symptoms showed axonal swelling & myelin degeneration
in the sciatic nerve.
Permethrin has no teratogenic or mutagenic
activity.
Permethrin has a low acute toxicity to rats,
mice, rabbits, & guinea-pigs, though the LD50 value varies considerably according to
the vehicle used & the cis-trans isomeric ratio. Signs of acute poisoning become
apparent within 2 hr of dosing & persist for up to 3 days. [1R,cis]- & [1R,trans]-permethrin belong to the type I group of pyrthroids,
which typically cause tremor (T-syndrome), incoordination, hyperactivity, prostration,
& paralysis. Core temperature is markedly incr during poisoning.
Oral subacute & subchronic toxicity studies of permethrin
have been performed in rats & mice at dose levels up to 10,000 mg/kg diet & for 14
days to 26 wk in duration. Changes detected at the higher level were an incr in liver/bw
ratio, hypertrophy in the liver, & clinical signs of poisoning such as tremor. The
no-observed-effects levels (NOEL) in rats ranged from 20 mg/kg diet (in studies lasting 90
days or 6 months) to 1500 mg/kg diet (in a 6-month study).
Permethrin caused a mild primary irritation
of the intact & abraded skin of rabbits but did not cause a photochemical irritation
reaction after exposure of treated areas of rabbit skin to uv light. Permethrin
did not cause a sensitization reaction in guinea-pigs.
Permethrin & cypermethrin were evaluated
for their ability to alter microsomal cytochrome p450 and NADPH cytochrome c reductase in
Long-Evans rats. When permethrin
(cis-trans=80:20) was orally admin to rats at 50 mg/kg bw/day, it incr cytochrome p450
after 4, 8, or 12 days of admin & NADPH cytochrome c reductase after 8 or 12 days,
whereas cypermethrin (alpah-cyano analog of permethrin)
did not induce either cytochrome p450 or the reductase. Neither of the two pyrethroids
altered body weight gain.
Hens were admin permethrin orally
(cis:trans=1:1) (as a 40% w/v solution in dimethylsulfoxide) at a daily dose level of 1
g/kg bw for 5 days. After 3 wk, the dosing regimen was repeated, & the animals were
maintained for an addtl period of 3 wk before being sacrificed. There were no signs of
neurological disturbance or mortality in any of the animals. All hens treated with
tri-ortho-cresyl phosphate (positive control) displayed clinical & histopathological
evidence of neurotoxicity, whereas none of the birds dosed with permethrin
showed any signs of intoxication. Histological exam of nerve tissue revealed no lesions.
Hence, permethrin was considered to have no
delayed neurotoxic potential such as that associated with certain organophosphates.
15 Adult hens were orally admin permethrin at
9 g/kg bw & again 21 days later. After a further 21 days, they were sacrificed. All
positive control animals (given tri-ortho-cresyl phosphate at 500 mg/kg) showed signs of
delayed neurotoxicity ranging from slight muscular incoordination to paralysis. No signs
of ataxia were recorded in any of the hens in the permethrin-treated
or negative control groups. Histopathological exam of the nervous tissues of permethrin-treated animals revealed none of the
degenerative changes noted in the tissues of the positive controls.
Behavioral observations were carried out on immature male Sprague-Dawley rats
habituated to inhalation of permethrin aerosols.
Habituation was carried out by exposing 3 groups of rats (5/group) to aerosols of permethrin firstly at 500 mg/cu m for 21 days then at
1000 mg/cu m for an addtl 21 days. Three other groups of rats (5/group) served as
controls; they were similarly treated but were not exposed to permethrin.
At the end of this conditioning period, all rats, including the controls, were exposed to
a permethrin aerosol at 5000 mg/cu m for 4 hr.
At the end of the habituation period, there were no differences in retention of avoidance
training or the ability to learn the same task between controls & aerosol exposed
groups. However, after exposure to permethrin at
5000 mg/cu m, the non-habituated control group of rats showed significantly lower
retention capacity compared with the habituated rats or with their own pre-exposure
performances. The non-habituated control rats also showed decr in coordination &
balance & a higher incidence of conflict behavior & tremors. The performance of
the rats in the habituated groups was not changed.
When groups of 10 males & 10 female Sprague-Dawley rats were given permethrin (25:75) (94.5% pure) at 4000, 6000, or 9000
mg/kg diet for 21 days, all animals developed severe trembling & lost weight. Some of
the highest dose rats of each sex died. Subsequent exam of brain, spinal cord, trigeminal
& dorsal root ganglia, proximal & distal root trunks, & terminal motor &
sensory nerves revealed no consistent histopathological abnormalities.
A detailed morphological evaluation of the nervous system was performed on rats in 2
long-term feeding studies. In the first, Long-Evans rats were fed diets containing permethrin at concn of 0, 20, 100, or 500 mg/kg diet
for 2 yr, & 5 male & 5 female randomly selected survivors from each group were
examined. In the second study, Long-Evans rats were fed diets containing permethrin
at concn of 0, 20, or 100 mg/kg diet for 3 successive generations, & 5 male & 5
female rats from each group were randomly selected from the third generation parental
animals. Exam of central & peripheral nerves & of extensive morphometric data
& teased myelinated fibers of distal sural & tibial nerves & of the maxillary
division of the fifth cranial nerve did not reveal any changes attributable to the feeding
of the pesticide.
In a short-term study designed to assess the effects of high concn of permethrin
on the sciatic nerve, male Wistar rats (10 per group) were fed permethrin
at dose levels of 0, 2500, 3000, 3750, 4500, 5000, & 7000 mg/kg diet for 14 days.
Clinical signs of acute poisoning & death occurred in the animals that were dosed at
5000 or 7000 mg/kg. Some rats that received the lower dose levels showed slight to
moderate tremors, & food consumption & growth were reduced in these animals. At
the two lowest dose levels, clinical signs of poisoning disappeared within the first week
whereas, at the higher dose levels, signs of poisoning persisted throughout the study.
Rats receiving permethrin at doses of up to 4500
mg/kg showed no ultra structural changes in their sciatic nerve. A variety of mild ultra
structural changes, such as vacuolation & swelling of unmyelinated fibres &
hypertrophy of Schwann cells, were observed in the nerves of rats receiving 5000 mg/kg.
When male & female Charles River rats (6 of each sex group) were fed permethrin at dose levels of 0 or 6000 mg/kg diet for
up to 14 days, severe clinical signs of poisoning were evident in all the permethrin treated rats. Only one permethrin
treated male survived the 14 day trial. Fragmented & swollen sciatic nerve axons &
myelin degeneration were observed in 4 out of 5 permethrin-reated
animals.
Female Sprague-Dawley rats (5-8 rats per group) /were fed/ permethrin
in the diet at levels of 0, 500, 1000, 1500, 2000, 2500, 3000, 3500, & 4000 mg/kg diet
from day 6 to day 15 of pregnancy. Laparotomy was performed on day 20 of gestation, &
the number of live fetuses was determined. Plancentae were excised & cleaned of
extraneous connective tissue. Analysis of the protein & glycogen contents of the
placentae on day 16 of pregnancy indicated that they were only influenced by very high
doses (2500-4000 mg/kg diet) of permethrin.
Analysis of variance indicated no significant effect of protein level, but the treatment
did decr the glycogen concn. No significant dose-related effects on implantational
sites/intrauterine fetuses were observed. These results appeared to confirm that permethrin possesses low mammalian toxicity.
In a 3 generation reproduction study, groups of 20 male & 20 female Wistar COBS
rats received permethrin (25:75) in the diet at
0, 5, 30, & 180 mg/kg bw/day during growth, mating, gestation, parturition, &
lactation for three generations, each with 2 litters. Fetal toxicity & teratogenicity
was assessed in the second pregnancy of the F2 generation. Treatment with permethrin had no effect on general behavior or
condition, food intake, body weight gain, or pregnancy rate of the dams, or on
parturition, sex ratio, or pup weight. A small number of rats of each group developed eye
abnormalities, including ocular hemorrhage & chronic glaucoma, but this was not
related to the treatment. Exam of F3b fetuses showed no treatment-related effect on sex
ratio, body weight, or the occurrence of visceral or skeletal abnormalities. This study
indicated that permethrin (25:75) has no effect
on the reproduction of rats at doses up to 180 mg/kg bw/day.
Groups of Long-Evans rats (10 males & 20 females per group) were fed permethrin at dose levels of 0, 20, & 100 mg/kg
diet in a 3-generation (two litters per generation) reproduction study. There was no
effect on mortality, mating, pregnancy, or fertility, with the exception of the F2 mating
index, which was reduced in both controls & treatment groups. Pup survival &
growth were unaffected. Hematological evaluations of F2 adults between the second &
third mating showed no unusual effects. This study indicated that dietary permethrin does not adversely affect reproduction in
the rat.
Mated female Dutch rabbits (18 per group) were orally admin permethrin
(at dose levels of 0, 600, 1200, or 1800 mg/kg bw/day) in 0.5% v/v aqueous Tween 80 from
days 6-18 inclusive of pregnancy. On day 29 pregnancy the animals were killed & their
uteri were examined for resorptions & live implantations. The fetuses were examined
for gross abnromalities of skeleton & soft tissue. At all dose levels, permethrin depressed body weight gain during dosing
& was embryotoxic at the two highest dose levels. It was toxic to the dams at 1800
mg/kg bw/day, but no teratogenic activity was detectable at any dose level.
Groups of Wistar (12 males & 24 females per group) were fed permethrin
at dose levels of 0, 500, 1000, & 2500 mg/kg diet for 12 wk. At 12 wk the animals were
mated to initiate a standard 3-generation (two litters per generation) reproduction study.
Clinical signs of acute poisoning (tremors, etc.) were noted, predominantely in females
given the highest dose. There were no effects attributed to permethrin
on fertility, gestation, viability of pups, sex ratio, litter size, or lactation. Ten male
& female weanlings from the second litter of the F3 generation were examined for
histopathological changes. Centrilobular hypertrophy & cytoplasmic eosinophilia were
observed at all dose levels, the incidence & severity of which appeared to be dose
dependent. Rats in the third litter of the F3 generation were sacrificed on day 12 of
gestation for teratogenic exam, but no abnormalities were observed. Based on the results
of this study, permethrin does not appear to
induce reproductive toxicity in rats.
When groups of 22 female Wistar rats received permethrin
(25:75) at 0 or 200 mg/kg bw in corn oil by daily oral gavage on days 6-16 (inclusive) of
pregnancy, treatment was without apparent effect on maternal body weight gain or general
conditions. The animals were sacrificed on day 20 so that their uterine contents could be
examined. Treatment had no effect on the number of corpora lutea, implantations, live
fetuses, early & late fetal deaths, or fetal abnormalities. Exam of the fetuses, which
included dissection & skeletal staining, showed no morphological effects of treatment.
These results indicate that permethrin (25:75)
at 200 mg/kg bw/day is not fetotoxic to rats.
Pregnant Sprague-Dawley rats (29-34 per group) were orally admin permethrin
at dose levels of 0, 10, 20, or 50 mg/kg bw from day 9 to 14 pregnancy. On day 20, approx
2/3 of the pregnant females were sacrificed & the remaining rats were allowed to
deliver & wean pups. After lactation, the pups were examined for behavior & for
growth & differentiation before being sacrificed at 6 wk of age & examined for
internal & external gross malformations. Pregnant females fed at the highest dose
showed toxic signs of poisoning, including ataxia, tremor, & a slight reduction in
body weight. There was no mortality, although fetal loss at the highest dose level was
slightly higher than that in the control animals. A slightly higher incidence of
non-ossified sternebra was noted at 50 mg/kg. The number of implantation sites & the
litter size were not affected, & growth & differentiation were similarly
unaffected. Internal & external exam showed that, with the exception of the slight
skeletal variation noted at 50 mg/kg, there were no permethrin
assoc changes. In those animals allowed to bear & wean pups, there were no notable
differences from control values with respect to gestation, implantation sites, delivery,
& numbers of live young. Growth & differentiation of the offspring did not appear
to be affected by permethrin, & there were
no abnormalities with respect to gross pathology or in the weights of major tissue &
organs at the conclusion of the study. permethrin
did not elicit a teratogenic effect in this bioassay.
In dominant lethal studies, permethrin
dissolved in corn oil was admin orally for 5 successive days to groups of male CD mice
(15/group) at doses of 15, 48, or 150 mg/kg. Each male mated with 16 virgin females, &
on the 12th day of gestation the females were killed. There was no dose related effect on
pregnancy or early or late fetal deaths. Admin of permethrin
thus had no dominant lethal effect on male mice. On the other hand, the positive control
(ethylmethanesulfonate) induced pre-implantation losses & the early death of embryos.
Permethrin (25:75) gave a negative response
when mouse lymphoma L5178Y cells were treated with permethrin
(up to 125 ug/ml) with or without activation.
Permethrin (4, 41, & 83 mg/kg/diet),
aspirin (200 mg/kg diet), & corn oil (2 mg/kg diet) were each admin to groups of 20
pre-impregnated Sprague-Dawley rats from day 6 to day 16 of gestation. The animals were
sacrificed on day 20 of gestation, & the fetuses were removed & examined for gross
abnormalities, sex, weight, & body length. The admin of aspirin (the positive control)
resulted in significantly lower body weight & length & a variety of abnormalities
including craniorachischisis in the fetuses. Permethrin,
admin to pregnant rats during gestation by intragastric intubation, did not appear to
present a teratogenic or lethal hazard to the developing fetus.
Pregnant CD rats (20 rats per group) were orally admin permethrin
at dose levels of 0, 22.5, 71.0, or 225 mg/kg from day 6 to day 16 of gestation. On day
20, the animals were sacrificed & the corpora lutea were examined. Somatic &
skeletal investigations were performed on the fetuses. No adverse toxicological response
was seen at the highest dose used. There were no abortions or maternal deaths & no
significant differences in pregnancy frequency, corpora lutea, or total number of
implantations between treated & control rats. Placental & fetal weights were
similar to those of the controls & no skeletal or structural abnormalities were
observed. Based upon the standard teratological rat bioassay, permethrin
did not show any teratological potential.
Groups of pregnant ICR mice (27 to 32 mice/group) were orally admin permethrin
at dose levels of 0, 15, 50, or 150 mg/kg bw from day 7 to day 12 of pregnancy. On day 18,
2/3 of the animals were sacrificed & examined for implantation & resorption sites.
Viable offspring were examined for somatic & skeletal abnormalities, & after 3 wk
of lactation, pups were examined for behavioral abnormalities & for differentiation
& growth. At 6 wk of age, all animals were sacrificed & subjected to internal
& external exam. There were no effects on maternal toxicity over the course of the
study. Growth & differentiation of pregnant females were not affected by permethrin nor were the number of implantation sites
for litter size adversely affected. The size of individual pups & the incidence of
gross external, internal, & skeletal abnormalities were not significantly different
from those in the control mice. Permethrin, at
dose levels up to including 150 mg/kg, did not appear to affect those animals allowed to
bear & wean young. The growth of young animals did not appear to differ from control
values, & 3 wk after weaning the surviving animals did not differ from controls with
respect to growth or major organ changes. There was no teatogenicity associated with permethrin in this mouse bioassay, although the
duration of dosing was a little too short to cover both the early & late stage of
organ development.
Permethrin was tested for its ability to
induce complete & partial chromosome loss in Drosophila melanogaster males by adding 5
mg/l (soaked onto a filter paper) to the feeding solution. Treated males were mated with
mus-302 repair-defective females to detect chromosome loss in the zygotes. Permethrin did not induce a significant incr in
chromosome loss, compared to negative controls.
The mutagenic activity of permethrin was
evaluated using the Ames test. There was no increase in the number of revertant colonies
at doses up to 2500 ug permethrin/plate in five
strains of Salmonella typhimurium (TA1535, TA1537, TA1538, TA98, & TA100) with or
without S9-mix prepared from rat liver or S9 prepared from PCB-treated mice.
Two reverse-mutation tests in Escherichia coli WP2 gave negative results.
In a host-mediated assay, permethrin (200
mg/kg body weight) was orally administered to ICR mice. The indicator organism, salmonella
typhimurium G46, harvested from the abdominal cavity of mice 3 hr after treatment, did not
reveal any mutagenic effect. In another host-mediated assay employing a similar test
system, (+)-trans-permethrin at dose levels of
600 and 3000 mg/kg body weight and (+)-cis-permethrin
at 21 and 54 mg/kg body weight gave negative results.
Permethrin was admin to groups of 8 males by
a single ip injection or by 5 daily injections at doses of 600, 3000, or 6000 mg/kg. The
cytogenetic effect on bone marrow cells was evaluated 24 hr after the single injection
& 6 hr after the last multiple dosing. No differences were observed in the rate of
chromosomal aberrations between any permethrin
treated groups & the vehicle controls. Two positive controls (trimethyl phosphate
& mitomycin C) produced a significantly higher incidence of chromosomal aberrations.
When tested for mutagenicity in V79 Chinese hamster cells, permethrin
& 5 other synthetic pyrethroids were shown to be non-mutagenic.
Permethrin & 6 other synthetic
pyrethroids were tested for mutagenicity in salmonella typhimurium TA98 & TA100
strains in the presence & absence of a metabolic activation system. All pyrethroids
tested gave negative results.
Wistar rats (60 of each sex per group) were fed permethrin
in the diet at dose levels of 0, 500, 1000, or 2500 mg/kg diet for 2 yr, & 12 rats of
each sex/group were sacrificed at 1 yr. Signs of poisoning such as tremors &
hyperexcitability were noted during the first 2 wk of dosing in the animals that received
the highest dose. There was no mortality attributed to permethrin,
& growth & food consumption were unaffected. There were no effects on
hematological, ophthalmological, urological, or other clinical chemistry parameters. Liver
aminopyrene N-demethylase activity was incr in all permethrin
treated animals. Bone marrow smears of the animals showed no unusual findings. Gross &
microsocopic exam of tissues & organs was performed after 1 & 2 yr, & all
animals that died with neoplastic changes were examined. Liver weights were higher after 1
yr of dosing in male & female rats that received permethrin
at 2500 mg/kg than in the control animals. After 2 yr, the liver weight & liver to
body weight ratios were higher in all permethrin
treated males than in the corresponding controls. In the females, higher values of
absolute & relative liver weights, compared to the controls, were recorded only in the
group of animals dosed at 1000 mg/kg. Kidney weight was also incr, predominantly in males,
at all dose levels. Hepatocyte vacuolation was seen at 1 year in males fed at the highest
dose level only & in females at all dose levels. The smooth endoplasmic reticulum
showed significant incr at 52 wk in both males & females at all dietary levels. At the
end of the study, notable endoplasmic reticulum incr were detected only at the highest
dose levels, although non-significant incr were noted to all dose levels in both males
& females. Exam of the sciatic nerve showed no effects attributed to permethrin.
No oncogenic effects were noted at any dose level.
The inhalation toxicity of technical grade permethrin
was determined in 3 species of lab animals. Male Hartley guinea pigs, male & female
Sprague-Dawley rats, & male & female beagle dogs were exposed to an aerosol of permethrin at concn of 125, 250, or 500 mg/cu m, 6
hr/day, 5 days/wk for 13 wk. The mass median diameter of the aerosol droplets was 5.1 um,
& 85% of the total droplets had a diameter of 1.0 um or less. At 500 mg/cu m, tremors
& convulsions occurred in the rats during the first wk of exposure but disappeared in
the second wk. There was no difference in oxygen consumption between control & treated
rats. Urine metabolite studies indicated that permethrin
was rapidly metabolized & excreted. Post-exposure experiments in male rats showed that
the hexobarbital induced sleeping time was significantly shortened after exposure at 500
mg/cu m but not at lower doses. No clinical signs of poisoning were observed in the guinea
pigs & dogs when exposed to aerosols of permethrin
under similar conditions. Pulmonary function, clinical chemistry parameters, & blood
cell counts were unaffected in the beagle dogs following exposure. No cmpd related gross
or microscopic pathological changes or other permanent changes were observed in the dogs,
rats, or guinea pigs as a result of permethrin
inhalation.
Long-Evans rats (60 males and 60 females per group) fed permethrin
in the diet at dose levels of 0, 20, 100, or 500 mg/kg for 2 yr did not reveal any
mortality or adverse effects on growth, food consumption, or behavior attributable to the
admin. Hematology, clinical chemistry, & urinalysis measurements were performed at
either 6 months or 1 yr & at the end of the study. There were no cmpd related effects
at the end of the study. There were no cmpd related effects on a wide variety of
parameters examined, & ophthalmological exam indicated no abnormalities. Blood glucose
levels were higher in the highest dose males at 24 months & in the highest dose
females at 18 months, compared to the values of the control animals. Two independent
evaluations of the histopathological data concluded that there was no oncogenic potential
for permethrin. While there was a dose dependent
incr in gross liver weight in both males & females, these values are small & not
statistically significant. The NOEL for general toxicity in this study was estimated to be
100 mg/kg.
SPF Alderly Park strain mice (70 males & 70 females/group) were fed permethrin (cis 35-45%; trans 65-55%) at dose levels
of 0, 250, 1000, or 2500 mg/kg diet for 2 yr. 10 males & 10 females were designated
for interim kills at 26 & 52 wk. The mortality rate was unaffected by the admin of permethrin. Growth was slightly decr at the 2 highest
dose levels at various periods during the study. At the interim sacrifice of 52 wk &
at the end of study, a significant dose dependent incr in liver to body weight ratio was
observed at the 2 highest dose levels in females (with 2500 mg/kg only at the end of the
study) & the highest dose level in males. Hepatic aminopyrene N-demethylase activity
was also substantially incr, although not consistently, in both male & female mice
given the highest dose. Gross & microscopic exam of tissues & organs (&
specific exam for hepatic neoplasia) did not reveal any significant carcinogenic effect as
a result of permethrin admin. Many of the
non-tumor abnormalities observed were considered to be those associated with aging of the
mice, characterized by incr eosinophilia of the centrilobular hepatocytes. Also, a decr in
vacuolation of the proximal tubular epithelium of the kidney was noted at all dietary
levels in males. A high incidence of lung adenomas was observed with all animals in the
study, but statistical analysis suggested that this was not related to permethrin
feeding. Electronmicroscopic exam of subcellular liver components showed a proliferation
of the smooth endoplasmic reticulum at dose levels of 1000 & 2500 mg/kg. No notable
effects on the sciatic nerve were found as the result of permethrin
admin.
CD-1 Strain mice (75 of each sex per group) were fed permethrin
in the diet for 104 wk. Alterations were made in the dietary dose levels during the course
of the study. From wk 1 to 19, the animals were given dose levels of 0, 20, 100, & 500
mg/kg diet. At wk 19, the dose level of 500 mg/kg was incr to 5000 mg/kg & maintained
for 2 wk before returning to 500 mg/kg. At wk 21 the 100 mg/kg dose was incr to 4000 mg/kg
& maintained for the remainder of the dosing period. Growth was inhibited in males at
4000 mg/kg. With the exception of a reduced blood glucose level in the animals receiving
4000 mg/kg dietary admin of permethrin had no
other effects on hematology or clinical chemistry parameters in the mouse. The liver
weight was higher than it was in control animals in both male & female animals at a
dose level of 500 mg/kg or more. In addtn, the heart weight was higher at 4000 mg/kg.
Neoplastic changes, not associated with dietary levels of permethrin,
were observed in some animals in all groups. While there was no direct effect with respect
to hepatic neoplasms, it was noted that hepatocellular hypertrophy, pleomorphism &
degeneration occurred in treated mice with incr frequency & appeared to show a dose
response relationship. No oncogenic effects were observed in the test animals.
In a study 0.1 ml of undiluted technical permethrin
(91.35 purity) was applied to the eyes of Japanese White rabbits. The eyes were washed
with distilled water 5 min or 24 hr after the application of permethrin.
No eye irritation was observed.
Undiluted permethrin applied to the eyes of
female rabbits caused minimal pain, redness, chemosis of the conjunctiva, and a slight
discharge.
Permethrin (25:75) (40% in corn oil) did not
produce any ocular effects when 0.1 ml was instilled into the ocular sac of New Zealand
rabbits.
In feeding experiments in dogs, the 90-day no-effect level was 200 ppm.
In 2 yr feeding trials, rats receiving 100 mg/kg diet showed no ill effects. No
mutagenic, teratogenic, or carcinogenic activity.
Permethrin caused mild primary irritation of
the intact or abraded skin of rabbits; it also caused mild conjunctivitis. Acneform
dermatitis was not produced when the compound was applied to the ears.
Even though permethrin is about 30 times more
toxic to houseflies than pyrethrinI, it is substantially less toxic to rats. The oral and
intravenous LD50 values in rats are 1,500 and >270 mg/kg, respectively. Other studies
indicate oral LD50 values of 3800 and 410 mg/kg in female rats for the undiluted compound
and for the active ingredient dissolved in an unsaturated oil, respectively. Dermal
application for 21 days elicited no toxicity.
In reproductive studies in mice, rats, and rabbits, oral doses of 200 to 400 mg/kg had
no effect on the fetus.
The Type I poisoning syndrome or "T syndrome" is produced by esters lacking
the alpha-cyano substituent and is characterized by restlessness, incoordination,
prostration, and paralysis in the cockroach, ascompared to the rat, which exhibits such
signs as sparring and aggressive behavior, enhanced startle response, whole body tremor,
and prostration. /Pyrethroid esters lacking the alpha-cyano substituent/
Synthetic pyrethroids have been shown to be toxic for fish, aquatic arthropods, &
honeybees in laboratory tests. But, in practical usage, no serious adverse effects have
been noticed because of the low rates of application & lack of persistence in the
environment. The toxicity of synthetic pyrethroids in birds & domestic animals is low.
/Synthetic pyrethroids/
The in vitro effects of pyrethroids on the mitogenic responsiveness of murine splenic
lymphocytes to concanavalin A and lipopolysaccharide were determined. Allethrin was the
most potent inhibitor, with effective concn in the range of 1X10-6 to 1.5X10-5 M. The
results support the possibility of immune suppression by pyrethroid exposure.
/Pyrethroids/
The type I pyrethroids /incl permethrin/
produce the simplest poisoning syndrome & produce sodium tail currents with relatively
short time constants. Poisoning closely resembles that produced by DDT & ... involves
a progressive development of fine whole-body tremor, exaggerated startle response,
in-coordinated twitching of the dorsal muscles, hyperexcitability, & death. The tremor
is assoc with a large incr in metabolic rate & leads to hyperthermia, which, with
metabolic exhaustion, is the usual cause of death. Respiration & blood pressure are
well sustained but plasma noradrenaline, lactate, & to a lesser extent adrenaline are
greatly incr.
Based on the signs of toxicity to mammals, & to cockroaches, pyrethroids may be
classified into two types: Type I & Type II cmpds. 1R-cis- & 1R-trans-permethrin belong to Type I. Electrophysiological
recording from dosed cockraoches reveal trains of cercal sensory spikes &, sometimes,
spike trains from the cercal motor nerves & the CNS. The signs of poisoning caused by
Type I pyrethroid cmpds are restlessness, incoordination, hyperactivity, prostration,
& paralysis.
Exposure of sensory nerve fibres from clawed frogs (Xenopus laevis) to permethrin (10-7 to 10-5 mol/l) resulted in marked
repetitive activity. This heightened activity was not observed in the motor fibres of
frogs that were similarly tested. Treatment of isolated lateral-line preparations of frogs
with permethrin (5x10-6 mol/l) also resulted in
pronounced repetitive activity.
Permethrin (cis, trans, & technical
grade) & deltamethrin, as representatives of the non-cyano- & cyano-containing
classes, respectively, of synthetic pyrethroids, were examined regarding their major site
of action on the mammalian nervous system in mice. ED50 values for the ability of both
types of pyrethroids to cause prostration & loss of righting reflex were estimated
following either intravenous or intracerebroventricular injections. The comparative
potencies of the 4 pyrethroids (deltamethrin >cis-permethrin
>technical grade permethrin >trans-permethrin) were the same following either route of
admin. All 4 cmpds tested showed a much greater potency (>200-fold for deltamethrin,
cis-permethrin, & technical grade permethrin & 85-fold for trans-permethrin)
after intracerebroventricular admin than after iv admin. In addtn, the poisoning symptoms
seen following direct central injection were almost identical to those obtained with
peripheral admin. These results suggest that poisoning from both classes of pyrethroids in
mammals is due predominantly to central mechanisms.
Non-Human Toxicity Values:
LD50 Rat oral 600 mg/kg
LD50 Rat iv >270 mg/kg
LD50 Rat oral 430-4000 mg/kg /cis:trans-isomer ratio of 40:60/
LD50 Rat oral 1.3 g/kg
LD50 Rat oral 6000 mg/kg /cis-: trans-isomer ratio of 20:80/
Ld50 Rat percutaneous > 4000 mg/kg
LD50 Rabbit percutaneous > 2000 mg/kg
LD50 Chicken oral >3000 mg/kg /cis-:trans-isomer ratio of 40:60/
LD50 Rat (female) 3,800 mg/kg /Undiluted compound/
LD50 Rat (female) 410 mg/kg /AI dissolved in an unsaturated oil/
LD50 Rat (male) oral (in water) 2949 mg/kg
LD50 Rat (female) oral (in water) >4000 mg/kg
LD50 Rat (male) oral (in corn oil) 430 mg/kg
LD50 Rat (female) oral (in corn oil) 470 mg/kg
LD50 Rat (male) dermal (in water) >5176 mg/kg
LD50 Rat (male) dermal >25000 mg/kg
LD50 Rat (female) dermal >4000 mg/kg
LD50 Mouse (female) oral (in water) >4000 mg/kg
LD50 Mouse (male & female) oral (in DMSO) 250-500 mg/kg
LD50 Mouse (male) oral (in corn oil) 650 mg/kg
LD50 Mouse (female) oral (in corn oil) 540 mg/kg
LD50 Mouse dermal >2500 mg/kg
LD50 Guinea pig oral (in water) >4000 mg/kg
LD50 Rabbit (female) oral (in water) >4000 mg/kg
LD50 Rabbit (female) dermal >2000 mg/kg
LD50 Hen oral >1500 mg/kg
LD50 Rat skin 2500 mg/kg
LD50 Rat subcutaneous 6600 mg/kg
LD50 Mouse ip 514 mg/kg
LD50 Mouse iv 31 mg/kg
Ecotoxicity Values:
LC50 Pimephales promelas (fathead minnow) 16.0 mg/l/96 hr (confidence limit 8.71- 29.6
mg/l), flow-through bioassay with measured concentrations, 25.4 deg C, dissolved oxygen
7.5 mg/l, hardness 45.7 mg/l calcium carbonate, alkalinity 41.6 mg/l calcium carbonate,
and pH 7.1.
LD50 Japanese quail >13,500 mg/kg /cis-:trans-isomer ratio of 40:60/
LC50 Bluegill sunfish 1.8 ug/l/48 hr /Conditions of bioassay not specified/
LC50 Rainbow trout 5.4 ug/l/48 hr /Conditions of bioassay not specified/
LC50 Brook trout (1.2g) @ 12 deg C 3.2 (2.2-4.8) ug/l/96 hr. Static bioassay without
aeration, pH 7.2-7.5, water hardness 40-50 mg/l as calcium carbonate and alkalinity of
30-35 mg/l. /Technical material 92.5%/
LC50 Brook trout (1.2 g) @ 12 deg C. 5.2 (3.5 - 7.9) ug/l/96/hr . Static bioassay
without aeration, pH 7.2-7.5, water hardness 40-50 mg/l as calcium carbonate and
alkalinity of 30-35 mg/l. /Liquid 5.7%/
LC50 Brook trout (1.2 g) @ 12 deg C 2.3 (1.4 - 3.7) ug/l/96/hr. Static bioassay without
aeration, pH 7.2-7.5, water hardness 40-50 mg/l as calcium carbonate and alkalinity of
30-35 mg/l. /Emulsifiable concentrate 13.3%/
Metabolism/Pharmacokinetics:
Metabolism/Metabolites:
Permethrin is rapidly metabolized in rats
& other species by ester cleavage & hydroxylation.
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.
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.
The proposed metabolic pathway for cis- and trans-permethrin
are /as follows/. The five principle sites of metabolic attack in both permethrin
isomers were 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 occurred to varying extent. cis-Permethrin was more stable then trans-permethrin, and the cis isomer yielded four faecally
excreted ester metabolites that resulted 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 were extensively excreted into the urine whereas the metabolites
retaining an ester bond were 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 were 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 was 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 were PBalc, PBacid-glycine and the sulfate of 3-(2'-hydroxyphenoxy)
benzoic acid (2'-OH-PBacid). [1RS,trans]- and [1RS,cis]-permethrin
showed no significant differences in metabolic fate in the rat from [1R,trans]- and
[1R,cis]-permethrin, respectively.
The metabolites are primarily 3-phenoxybenzyl alcohol and its oxidation products, which
are rapidly excreted in urine. The other hydrolysis products are dimethyl or dichlorovinyl
acids, which are partially hydroxylated and rapidly excreted. In radiolabel experiments,
no accumulation of the parent compounds or of their metabolites was observed.
Less than 2% of an applied topical dose is absorbed systemically. The compound is
rapidly metabolized by ester hydrolysis to inactive metabolites that are excreted in the
urine. Permethrin persists on hair for at least
10 days.
Phosphoinositide breakdown in guinea pig cerebral cortical synaptoneurosomes induced by
the Type I pyrethroids allethrin, resmethrin, and permethrin
and the Type II pyrethroid deltamethrin and fenvalerate were investigated with various
receptor agonists as well as sodium channel blockers and agents. Phosphoinositid breakdown
was determined from inositol phosphate formation by tritiated inositol labeled
synaptoneurosomes. All five pyrethroids dose dependently induced phosphoinositide
breakdown. Type II pyrethroids exhibited higher potency and deltamethrin was more
efficacious than the Type I pyrethroids. Five micromolar tetrodotoxin, a blocker of
voltage dependent sodium channels, partially inhibited deltamethrin (85%) and fenvalerate
(60%) responses but not allethrin or resmethrin. Fenvalerate induced stimulation of
phosphoinositide breakdown was additive with stimulation elicited by the receptor agonists
carbamylcholine (1 mM) and norepinephrine (1000 uM) but less than additive with the sodium
channel agents batrachotoxin, pumiliotoxin-B, and scorpion venom. Allethrin (100 uM) was
less than additive with receptor agonists or sodium channel agents and actually
significantly inhibited response to scorpion venom. Effects for 100 uM allethrin with
either fenvalerate or deltamethrin were not different from allethrin alone. Ten micromolar
allethrin slightly decreased response to 10 to 100 uM deltamethrin. The local anesthetic
dibucaine, a sodium channel activation inhibitor, completely blocked deltamethrin induced
phosphoinositide breakdown but was much less effective in inhibiting allethrin response.
It appears likely that Type I pyrethroids induce phosphoinositide breakdown through a
mechanism other than sodium channel activation while Type II pyrethroids act in a manner
analogous to other sodium channel agents.
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 addtl 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/
Pyrethrins are reportedly inactivated in the GI tract following ingestion. In animals,
pyrethrins are rapidly metabolized to water soluble, inactive compounds. /Pyrethrins/
Synthetic pyrethroids are generally metabolized in mammals through ester hydrolysis,
oxidation, and conjugation, and there is no tendency to accumulate in tissues. In the
environment, synthetic pyrethroids are fairly rapidly degraded in soil and in plants.
Ester hydrolysis and oxidation at various sites on the molecule are the major degradation
processes. /Synthetic pyrethroids/
Absorption, Distribution & Excretion:
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, &
growth & 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 & not to incr with time. Analysis of individual
cis & 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 & 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% & 25-36% of the trans & 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.
To assess the human tolerance, absorption, & persistence of permethrin
when used against human lice, ten adult volunteers (four men, six women) were treated with
15-40 ml of permethrin (25:75) (1%) head louse
solution. Their hair was allowed to dry naturally & then washed with baby shampoo.
Urine samples were collected at 0-24, 24-48, 120-144, & 336-360 hr to measure dermal
absorption. Permethrin excretion during the
first 24 hr was only about 1% of the applied dose, while the cumulative maximum over 14
days was only about 5.5 mg.
To assess the safety of permethrin dusts for
the control of human body lice, approximately 350 people were individually dusted with 50
g of powder containing either 2.5 or 5.0 g permethrin/kg.
Urine samples, taken at the time of treatment and subsequently, indicated that maximal
absorption of permethrin was 39 ug/kg, 24 hr
after treatment.
Ten scabies patients (five men and five women) had about 25 g (range 21-32 g) of a 5% permethrin cream applied to the skin of the whole
body, with the exception of the head and neck. Dermal absorption of permethrin
was calculated from the quantity of conjugated and nonconjugated cis- and
trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (CVA) metabolites of
permetherin determined in the urine. In samples of urine collected by seven patients one
and two days after application of the permethrin
cream, 414 and 439 ug mean total CVA were found, respectively. The mean total CVA in the
urine of three patients who collected their urine in the same container for two days was
1435 ug. The urinary concentration of trans-CVA varied during the first 48 hours from 0.11
to 1.07 ug/ml and that of the cis-isomer form 0.02 to 0.21 ug/ml. CVA was still detectable
in the urine of three patients after a week and in the urine of one patient, reported to
be an alcoholic, after two weeks. The absorption of permethrin
over the first 48 hours after application was estimated from the urinary CVA excretion
levels to be 6 mg (range, 3-11 mg), i.e., 0.5% of the dose applied.
Penetration of pesticides through the GI tract compound: permethrin;
species: mouse; application site: oral; solvent: emulfor; penetration parameter: 39%, 1
hr; Method: GI content. /From table/
Dermal penetration of pesticides. Compound: permethrin;
species; mouse; Application site: dermal; Solvent: acetone; Penetration-parameter: 80%, 1
hr; Method: patch. /From table/
Dermal penetration of pesticides. Compound: permethrin;
species: roach; application site: dermal; solvent: acetone; penetration: 24%, 1 hr;
Method: patch. /From table/
Dermal penetration of pesticides. Compound: permethrin;
species: hornworm; application site: dermal; solvent: acetone; penetration parameters:
15%, 1 hr; Method: patch. /From table/
Dermal penetration of pesticides. Compound: permethrin;
species: frog; Applicaton site: dermal; Solvent: acetone; Penetraton parameters: 20%, 1
hr; Method: patch. /From table/
A 25% water-wettable powder formulation of permethrin
was applied as an indoor residual spray at a target dosage of 0.5 g/sq m. One bagger, one
mixer, and three spraymen treated a village in 2 days. Each man wore overalls (washed
daily) shoes, and a hat. The mixer wore a cartridge-type respirator and rubber gloves. The
bagger wore the same plus an apron. The spraymen did not wear masks. All practiced good
personal hygiene. The men were examined before and 1 day after exposure. No complaints
were received, and no abnormalities were detected. Based on the measurement of metabolites
in the urine, it was estimated that one sprayman absorbed from 1 to 2 mg in each 12-hour
period of work, but that the other men absorbed < 1 mg/period. Protective clothing of
the spraymen was the same, and the man who absorbed more had sprayed only slightly more.
Whereas permethrin is relatively stable to
air and light, rats readily metabolize both the [1R-trans]- and [1C-cis]-esters by ester
cleavage, by hydroxylaton of a geminal dimethyl group in the acid or the pheoxy group of
the alcohol, and by conjugation of the resulting carboxylic acids and phenols. The
metabolites are quickly excreted and do not persist significantly in the tissues. In spite
of the rapid metabolism of each dose, residues of unmetabolized compound did persist 12 or
13 days in mild fat and in other fat of cows that received (14)C-permethrin
by mouth at a rate of about 1 mg/kg for 3 consecutive days.
Less than 2% of an applied topical dose is absorbed systemically. The compound is
rapidly metabolized by ester hydrolysis to inactive metabolites that are excreted in the
urine. Permethrin persists on hair for at least
10 days.
A study was conducted to define permethrin
toxicokinetics in Sprague-Dawley rats after iv (iv) administration and to assess its oral
bioavailability. Orally dosed rats received a single dose of 460 mg/kg by gastric
intubation. Injected rats received 46 mg/kg iv. All animals were sacrificed at 0.25, 0.5,
1, 2, 3, 4, 6, 8, 12, 24, or 48 hr after dosing. For permethrin
the elimination half life and the mean residence time from plasma were 8.67 and 11.19 hr
after iv and 12.37 and 17.77 hr after oral administration. The total plasma clearance was
not influenced by dose concentration or route and reached a value of 0.058 l/hr. After a
single oral dose permethrin was absorbed slowly.
The maximum plasma concentration was 49.46 ug/milliliter. The oral bioavailability of permethrin was 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 maximum amounts of permethrin
in cerebellum, hippocampus, caudata 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,
suggesting an accumulation of pyrethroids by nervous tissue itself. The metabolites of permethrin, m-phenoxybenzyl 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.
/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/
In spraying trials in Kenya it was estimated that permethrin
absorption did not exceed 2 mg per 12 hr period. After oral dosage of 2 or 4 mg permethrin, urinary excretion accounted for 18 or 35%
of the dose, with most being excreted over the first 12 hr.
Biological Half-Life:
A study was conducted to define permethrin
toxicokinetics in Sprague Dawley rats after iv administration and to assess its oral
bioavailability. Orally dosed rats received a single dose of 460 mg/kg by gastric
intubation. Injected rats received 46 mg/kg intravenously. All animals were sacrificed at
0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, or 48 hr after dosing. For permethrin
the elimination half life and the mean residence time from plasma were 8.67 and 11.19 hr
after iv and 12.37 and 17.77 hr after oral administration. The total plasma clearance was
not influenced by dose concentration or route and reached a value of 0.058 l/hr. After a
single oral dose permethrin was absorbed slowly.
The maximum plasma concentration was 49.46 ug/ml. The oral bioavailability of permethrin was 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 maximum amounts of permethrin
in cerebellum, hippocampus, caudata 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,
suggesting an accumulation of pyrethroids by nervous tissue itself. The metabolites of permethrin, m-phenoxybenzyl 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.
Mechanism of Action:
1RS-cis-Permethrin and 1RS-trans-permethrin cause tremor (known as T-syndrome) when
injected intravenously into rats at a dose level of more than 270 mg/kg body weight. The
onset of the T-syndrome is usually rapid. Rats suffering from T-syndrome exhibit
aggressive sparring behavior and increased sensitivity to external stimuli. This is
followed by the appearance of a slight tremor, which gradually becomes more severe and
finally reaches a state of prostration and vigorous whole body tremor. The core
temperature is markedly increased during poisoning; this may result from the excessive
muscular activity associated with tremor.
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.
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 partical
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 incr sodium entry. /Pyrethroids/
The interaction of a series of pyrethroid insecticides with the sodium channels in
myelinated nerve fibers of the clawed frog, Xenopus laevis, was investigated using the
voltage clamp technique. Of 11 pyrethroids, 9 insecticidally active cmpd induced a slowly
decaying sodium tail current on termination of a step depolarization, whereas the sodium
current during depolarization was hardly affected. /Pyrethroids/
Mode of action of pyrethrum & related cmpd has been studied more in insects &
in other invertebrates than in mammals. This action involves ion transport through the
membrane of nerve axons &, at least in invertebrates & lower vertebrates, it
exhibits a negative temperature coefficient. In both of these important ways & in many
details, the mode of action of pyrethrin & pyrethroids resembles that of DDT.
Esterases & mixed-function oxidase system differ in their relative importance for
metabolizing different synthetic pyrethroids. The same may be true of the constituents of
pyrethrum, depending on strain, species, & other factors. /Pyrethrins and pyrethroids/
Type I Pyrethroid esters /lacking the alpha-cyano substituents/ affect sodium channels
in nerve membranes, causing repetitive (sensory, motor) neuronal discharge and a prolonged
negative afterpotential, the effects being quite similar to those produced by DDT.
/Pyrethroid esters lacking the alpha-cyano substituent/
The interactions of natural pyrethrins and 9 pyrethroids with the nicotinic
acetylcholine (ACh) receptor/channel complex of Torpedo electronic organ membranes were
studied. None reduced (3)H-ACh binding to the receptor sites, but all inhibited
(3)H-labeled perhydrohistrionicotoxin binding to the channel sites in presence of
carbamylcholine. Allethrin inhibited binding noncompetitively, but (3)H-labeled imipramine
binding competitively, suggesting that allethrin binds to the receptor's channel sites
that bind imipramine. The pyrethroids were divided into 2 types according to their action:
type A, which included allethrin, was more potent in inhibiting (3)H-H12-HTX binding and
acted more rapidly. Type B, which included permethrin,
was less potent and their potency increased slowly with time. The high affinities that
several pyrethroids have for this nicotinic ACh receptor suggest that pyrethroids may have
a synaptic site of action in addition to their well known effects on the axonal channels.
/Pyrethrins and Pyrethroids/
The primary target site of pyrethroid insecticides in the vertebrate nervous system is
the sodium channel in the nerve membrane. Pyrethroids without an alpha-cyano group
(allethrin, d-phenothrin, permethrin, and
cismethrin) cause a moderate prolongation of the transient increase in sodium permeability
of the nerve membrane during excitation. This results in relatively short trains of
repetitive nerve impulses in sense organs, sensory (afferent) nerve fibers, and, in
effect, nerve terminals. On the other hand the alpha-cyano pyrethroids cause a long
lasting prolongation of the transient increase in sodium permeability of the nerve
membrane during excitation. This results in long-lasting trains of repetitive impulses in
sense organs and a frequency-dependent depression of the nerve impulse in nerve fibers.
The difference in effects between permethrin and
cypermethrin, which have identical molecular structures except for the presence of an
alpha-cyano group on the phenoxybenzyl alcohol, indicates that it is this alpha-cyano
group that is responsible for the long-lasting prolongation of the sodium permeability.
Since the mechanisms responsible for nerve impulse generation and conduction are basically
the same throughout the entire nervous system, pyrethroids may also induce repetitive
activity in various parts of the brain. The difference in symptoms of poisoning by
alpha-cyano pyrethroids, compared with the classical pyrethroids, is not necessarily due
to an exclusive central site of action. It may be related to the long-lasting repetitive
activity in sense organs and possibly in other parts of the nervous system, which, in a
more advance state of poisoning, may be accompanied by a frequency-dependent depression of
the nervous impulse. /Synthetic pyrethroids/
Pyrethroids also cause pronounced repetitive activity and a prolongation of the
transient increase in sodium permeability of the nerve membrane in insects and other
invertebrates. Available information indicates that the sodium channel in the nerve
membrane is also the most important target site of pyrethroids in the invertebrate nervous
system. /Synthetic pyrethroids/
Interactions:
Phosphoinositide breakdown in guinea pig cerebral cortical synaptoneurosomes induced by
the Type I pyrethroids allethrin, resmethrin, and permethrin
and the Type II pyrethroid deltamethrin and fenvalerate were investigated with various
receptor agonists as well as sodium channel blockers and agents. Phosphoinositide
breakdown was determined from inositol phosphate formation by tritiated inositol labeled
synaptoneurosomes. All five pyrethroids dose dependently induced phosphoinositide
breakdown. Type II pyrethroids exhibited higher potency and deltamethrin was more
efficacious than the Type I pyrethroids. Five micromolar tetrodotoxin, a blocker of
voltage dependent sodium channels, partially inhibited deltamethrin (85%) and fenvalerate
(60%) responses but not allethrin or resmethrin. Fenvalerate induced stimulation of
phosphoinositide breakdown was additive with stimulation elicited by the receptor agonists
carbamylcholine (1 mM) and norepinephrine (1000 uM) but less than additive with the sodium
channel agents batrachotoxin, pumiliotoxin-B, and scorpion venom. Allethrin (100 uM) was
less than additive with receptor agonists or sodium channel agents and actually
significantly inhibited response to scorpion venom. Effects for 100 uM allethrin with
either fenvalerate or deltamethrin were not different from allethrin alone. Ten micromolar
allethrin slightly decreased response to 10 to 100 uM deltamethrin. The local anesthetic
dibucaine, a sodium channel activation inhibitor, completely blocked deltamethrin induced
phosphoinositide breakdown but was much less effective in inhibiting allethrin response.
It appears likely that Type I pyrethroids induce phosphoinositide breakdown through a
mechanism other than sodium channel activation while Type II pyrethroids act in a manner
analogous to other sodium channel agents.
/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/
Pharmacology:
Therapeutic Uses:
MEDICATION (VET): ectoparasiticide
Permethrin is a synthetic pyrethroid that has
low mammalian toxicity and an insecticidal effectiveness higher that of the natural
pyrethrins. Because of its high ovicidal activity and persistence on hair, a properly
applied 1% cream rinse preparation eliminates head lice infestation after a single
application. Fewer than 1% of patients have required retreatment after seven days.
Permethrin is stressed as a photostable
insecticide that is very effective against a large variety of insects and mites with low
mammalian toxicity and virtually no allergic side effects. Only 10-20 min after
application, permethrin (1% cream rinse or 0.5%
in ethanol) proved to be safe, reliable and cosmetically acceptable in the treatment of
infestations with head lice and the prevention of reinfestations, and also in failures
with lindane owing to the development of tolerance in the lice. The same was true of 5% permethrin cream (2.5% in children below 5 yr of age)
used in the treatment of scabies. Permethrin is
absorbed percutaneously in only small amounts, is metabolized rapidly in the skin and
excreted in the urine. A single "head to toe" application is ideal for
eradication programs allowing lice to be targetted and the prevalence of secondary
bacterial infections decreased at the same time.
Permethrin is recommended in scabies therapy
in premature infants, small children, patients with seizures and neurological
complications, in treatment failures with lindane entailing the need to repeat the
therapy, in scabies crustosa and in pregnant women and nursing mothers.
Crusted (Norwegian) scabies, a rare variant of ordinary scabies, is a highly contagious
infection in which the skin is infested with thousands to millions of mites. The infection
is frequently overlooked because of its atypical presentations. Patients with cognitive
deficiency or an immunodeficiency disorder (including immunosuppressive therapy) are
predisposed to developing crusted scabies. The infection often presents as generalized
dermatitis with crusted hyperkeratosis on the palms and soles. Diagnosis is made by
examining skin scrapings from the crusted lesions. Lindane is the scabicide most widely
used in the treatment of crusted scabies. Eradication frequently requires repeated
applications, and care must be taken to avoid lindane toxicity. Permethrin
cream is as efficacious as lindane in the treatment of ordinary scabies. Because of its
wider margin of safety, permethrin may become
the preferred treatment for crusted scabies.
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/
In controlled clinical trials, an experimental 5% dermal cream was effective against
scabies (investigational use).
Drug Warnings:
The safety and effectiveness of permethrin in
children less than 2 years of age have not been established.
Patients who cannot tolerate chrysanthemums, pyrethrins, and other synthetic
pyrethroids may not tolerate permethrin.
Interactions:
Phosphoinositide breakdown in guinea pig cerebral cortical synaptoneurosomes induced by
the Type I pyrethroids allethrin, resmethrin, and permethrin
and the Type II pyrethroid deltamethrin and fenvalerate were investigated with various
receptor agonists as well as sodium channel blockers and agents. Phosphoinositide
breakdown was determined from inositol phosphate formation by tritiated inositol labeled
synaptoneurosomes. All five pyrethroids dose dependently induced phosphoinositide
breakdown. Type II pyrethroids exhibited higher potency and deltamethrin was more
efficacious than the Type I pyrethroids. Five micromolar tetrodotoxin, a blocker of
voltage dependent sodium channels, partially inhibited deltamethrin (85%) and fenvalerate
(60%) responses but not allethrin or resmethrin. Fenvalerate induced stimulation of
phosphoinositide breakdown was additive with stimulation elicited by the receptor agonists
carbamylcholine (1 mM) and norepinephrine (1000 uM) but less than additive with the sodium
channel agents batrachotoxin, pumiliotoxin-B, and scorpion venom. Allethrin (100 uM) was
less than additive with receptor agonists or sodium channel agents and actually
significantly inhibited response to scorpion venom. Effects for 100 uM allethrin with
either fenvalerate or deltamethrin were not different from allethrin alone. Ten micromolar
allethrin slightly decreased response to 10 to 100 uM deltamethrin. The local anesthetic
dibucaine, a sodium channel activation inhibitor, completely blocked deltamethrin induced
phosphoinositide breakdown but was much less effective in inhibiting allethrin response.
It appears likely that Type I pyrethroids induce phosphoinositide breakdown through a
mechanism other than sodium channel activation while Type II pyrethroids act in a manner
analogous to other sodium channel agents.
/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/
Environmental Fate & Exposure:
Environmental Fate/Exposure Summary:
Permethrin's production and use as an
insecticide, acaricide, and nematocide is expected to result in its direct release to the
environment. If released to air, a vapor pressure of 2.18X10-8 mm Hg at 25 deg C indicates
permethrin will exist in both the vapor and
particulate phases in the ambient atmosphere. Vapor-phase permethrin
will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl
radicals and ozone; the half-lives for these reactions in air are estimated to be 9.8
hours and 49 days, respectively. Particulate-phase permethrin
will be removed from the atmosphere by wet and dry deposition. If released to soil, permethrin is expected to have no mobility based upon
a range of Koc values from 10,471 to 86,000. Volatilization from moist soil surfaces is
expected to be an important fate process based upon an estimated Henry's Law constant of
1.9X10-6 atm-cu m/mole. However, adsorption to soil is expected to attenuate
volatilization. In soil, the photolysis half-life is 30 days. The biodegradation half-life
of permethrin in an aerobically incubated soil
was less than 4 weeks. If released into water, permethrin
is expected to adsorb to suspended solids and sediment based upon its Koc values. The
biodegradation half-life of permethrin in a
sediment-seawater solution was less than 2.5 days. Volatilization from water surfaces is
expected to be an important fate process based upon this compound's estimated Henry's Law
constant. Estimated volatilization half-lives for a model river and model lake are 26 days
and 290 days, respectively. However, volatilization from water surfaces is expected to be
attenuated by adsorption to suspended solids and sediment in the water column. BCF values
for rainbow trout and sheepshead minnow of approx 560 and 480, respectively, suggest
bioconcentration in aquatic organisms is high. At pH 5 and pH 7, permethrin
is stable towards abiotic hydrolysis; at pH 9, the abiotic hydrolysis half-life is about
50 days. The photolysis half-life in water is 33 days. Occupational exposure to permethrin may occur through inhalation and dermal
contact with this compound at workplaces where permethrin
is produced or used. Monitoring data indicate that the general population may be exposed
to permethrin via inhalation of ambient air from
aerial spraying, ingestion of food, and with the household use of insecticides containing permethrin. (SRC)
Probable Routes of Human Exposure:
Occupational exposure to permethrin may occur
through inhalation and dermal contact with this compound at workplaces where permethrin is produced or used(SRC). Monitoring data
indicate that the general population may be exposed to permethrin
via inhalation of ambient air and ingestion of food, and with the household use of
insecticides containing permethrin(SRC). In
Japan, the concn of permethrin in the air near a
spreader's mouth area was 14.6 ug/cu m during application of the pesticide(1).
Permethrin is applied to several crops via
aerial or ground spraying(1). In pesticide formulating plants, exposure to permethrin may be from spillage; furthermore, there is
a high potential for exposure at mixing and bagging stations(2). Crop workers may be
exposed during application; however, their main exposure results from contact with treated
foliage or to pesticide or pesticide-contaminated material made airborn through agitation
of foliage during work activity(2). Incidental to treating a crop, some pesticides, such
as permethrin, may drift onto workers in
neighboring fields or in nearby suburban areas without there being any intent to treat
those areas(2). Therefore exposure of the general population to permethrin
may occur through inhalation and dermal contact resulting from spraying nearby areas(2).
According to a pilot investigation of pesticides in 9 homes in Jacksonville, FL during
August of 1985, potential respiratory exposure to permethrin
was estimated in 1 home using a personal monitor carried by a resident of each
household(1).
Body Burden:
The concn 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 a 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).
Average Daily Intake:
The average daily intake (AVDI) of permethrin
in 8 population groups in 1982-1984 was determined according to the FDA's monitoring
program for chemical contaminants in the U.S. food supply (Total Diet Study or Market
Basket Study). In 6-11 month old infants, the AVDI was 1.2 ng/kg-body weight-per day. In 2
yr old toddlers, the AVDI was 5.6 ng/kg-body weight-per day. In 14-16 year old females,
the AVDI was 3.3 ng/kg-body weight-per day. In 14-16 year old males, the AVDI was 3.0
ng/kg-body weight-per day. In 25-30 year old females, the AVDI was 5.0 ng/kg-body
weight-per day. In 25-30 year old males, the AVDI was 4.1 ng/kg-body weight-per day. In
60-65 year old females, the AVDI was 6.5 ng/kg-body weight-per day. In 60-65 year old
males, the AVDI was 5.4 ng/kg-body weight-per day(1).
The average daily intake (AVDI) of permethrin
(total) in 8 population groups in 1986-1991 was determined according to the FDA's
monitoring program for chemical contaminants in the U.S. food supply (Total Diet Study or
Market Basket Study). In 6-11 month old infants, the AVDI was 4.7 ng/kg-body weight-per
day. In 2 yr old toddlers, the AVDI was 7.1 ng/kg-body weight-per day. In 14-16 year old
females, the AVDI was 3.6 ng/kg-body weight-per day. In 14-16 year old males, the AVDI was
4.2 ng/kg-body weight-per day. In 25-30 year old females, the AVDI was 5.7 ng/kg-body
weight-per day. In 25-30 year old males, the AVDI was 4.6 ng/kg-body weight-per day. In
60-65 year old females, the AVDI was 5.9 ng/kg-body weight-per day. In 60-65 year old
males, the AVDI was 5.9 ng/kg-body weight-per day(1).
The average daily intake (AVDI) of permethrin
(total) in 8 population groups in 1984-1996 was determined according to the FDA's
monitoring program for chemical contaminants in the U.S. food supply (Total Diet Study or
Market Basket Study). In 6-11 month old infants, the AVDI was 44.1 ng/kg-body weight-per
day. In 2 yr old toddlers, the AVDI was 12.8 ng/kg-body weight-per day. In 14-16 year old
females, the AVDI was 5.5 ng/kg-body weight-per day. In 14-16 year old males, the AVDI was
7.6 ng/kg-body weight-per day. In 25-30 year old females, the AVDI was 7.7 ng/kg-body
weight-per day. In 25-30 year old males, the AVDI was 7.0 ng/kg-body weight-per day. In
60-65 year old females, the AVDI was 12.4 ng/kg-body weight-per day. In 60-65 year old
males, the AVDI was 11.5 ng/kg-body weight-per day(1).
Artificial Pollution Sources:
Permethrin's production and use as an
insecticide, acaricide, and nematocide(1) is expected to result in its direct release to
the environment(SRC).
Environmental Fate:
TERRESTRIAL FATE: Based on a classification scheme(1), Koc values ranging from 10,471
to 86,000(2,3), indicates that permethrin is
expected to be immobile in soil(SRC). Volatilization of permethrin
from moist soil surfaces is expected to be an important fate process(SRC) given an
estimated Henry's Law constant of 1.9X10-6 atm-cu m/mole(SRC), derived from its vapor
pressure, 2.18X10-8 mm Hg(2), and water solubility, 6.00X10-3 mg/l(2). 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(2). The biodegradation half-life of permethrin
in aerobically incubated soil was less than 4 weeks, and the degradation of the
trans-isomer is more rapid than the cis-isomer(4). 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(5). 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(4).
Field dissipation half-lives for permethrin
range from 6 to 106 days(2).
AQUATIC FATE: Based on a classification scheme(1), Koc values ranging from 10,471 to
86,000(2,3), indicates that permethrin is
expected to adsorb to suspended solids and sediment(SRC). Volatilization from water
surfaces is expected(4) based upon an estimated Henry's Law constant of 1.9X10-6 atm-cu
m/mole(SRC), derived from its vapor pressure, 2.18X10-8 mm Hg(2), and water solubility,
6.00x10-3 mg/l(2). Using this Henry's Law constant and an estimation method(4),
volatilization half-lives for a model river and model lake are 26 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 is 336 years if adsorption is
considered(5). At pH 5 and pH 7, permethrin is
stable towards abiotic hydrolysis(2); at pH 9, the abiotic hydrolysis rate constant is
0.0139 per day at 25 deg C(2) which corresponds to a half-life of 50 days(SRC). According
to a classification scheme(6), BCF values of approx 560 and 480 for rainbow trout
(Oncorhynchus mykiss) and sheepshead minnow (Cyprinodon vagiegatus), respectively(7,8),
suggests the potential for bioconcentration in aquatic organisms is high(SRC). In water,
the photolysis rate constant is 0.021 per day(2); this corresponds to photodegradation
half-life of 33 days(SRC). 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(9). The
photolysis half-life of permethrin in seawater
exposed to outdoor light was determined to be 14 days(8). The biodegradation half-life of permethrin in a sediment-seawater solution was less
than 2.5 days; under sterile conditions there was no significant change in permethrin concn(8).
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 2.18X10-8 mm Hg at 25 deg 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 9.8 hours(SRC), calculated from its rate constant of 3.9X10-11 cu cm/molecule-sec at 25
deg 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 deg C(4).
Particulate-phase permethrin may be removed from
the air by wet and dry deposition(SRC). Permethrin
absorbs light in the environmental spectrum(5) and has the potential for direct
photolysis(SRC).
Environmental Biodegradation:
Pure cultures of Bacillus cereus, Pseudomonas fluorescens, and Achromobacter sp.
transformed permethrin to
3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid, 3-phenoxybenzyl alcohol,
3-phenoxy benzoic acid, and 4-hydroxy-3-phenoxybenzoic acid; half-life of less than 5
days(1).
AEROBIC: The half-life of permethrin in
aerobically incubated soil is less than 4 weeks, and the degradation of the trans isomer
is more rapid than the cis isomer(1). Permethrin
was stable in sterile Hagerstown silty clay loam indicating that any degradation probably
was microbial(2); as expected ester hydrolysis predominated in non-sterile soil(2). 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(2). The half-life in a sediment-seawater
solution was less than 2.5 days; under sterile conditions there was no significant change
in permethrin concn(3).
ANAEROBIC: 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(1).
Environmental Abiotic Degradation:
The rate constant for the vapor-phase reaction of permethrin
with photochemically-produced hydroxyl radicals has been estimated as 3.90X10-11 cu
cm/molecule-sec at 25 deg C(1). This corresponds to an atmospheric half-life of about 9.8
hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(2). The rate
constant for the vapor-phase reaction of permethrin
with photochemically-produced ozone has been estimated as 2.33X10-17 cu cm/molecule-sec at
25 deg C(2). This corresponds to an atmospheric half-life of about 49 days at an
atmospheric concentration of 7X10+11 ozone molecules per cu cm(3). At pH 5 and pH 7, permethrin is stable towards abiotic hydrolysis(4); at
pH 9, the abiotic hydrolysis rate constant is 0.0139 per day at 25 deg C(4) which
corresponds to a half-life of 50 days(SRC). In water and soil, the photolysis rate
constants are 0.021 and 0.023 per day, respectively(4); this corresponds to
photodegradation half-lives of 33 and 30 days, respectively(SRC). The photodegradation
rate of permethrin on thin films in the 295-305
nm wavelength region was determined to range from 15.9X10-7 to 4.7X10-7 1/sec-1 which
corresponds to a half-life of 5-17 days, respectively(5). 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(6). The photolysis half-life of permethrin
in seawater exposed to outdoor light was determined to be 14 days(7).
Environmental Bioconcentration:
The BCF values for rainbow trout (Oncorhynchus mykiss) and sheepshead minnow
(Cyprinodon vagiegatus) were approximately 560 and 480, respectively(1,2). According to a
classification scheme(3), these BCF values suggest the potential for bioconcentration in
aquatic organisms is high(SRC). A BCF of 1,900 was also reported for oysters(2). Insect
BCF values after 6 hr of exposure to sublethal permethrin
concns were 18, 30, 7, 4, and 24 for black fly, caddisfly, damsefly, water scavenger, and
mayfly, respectively(4).
Soil Adsorption/Mobility:
Koc values for permethrin range from 10,471
to 86,000(1). Koc values for silt loam (Ohio), sandy loam (Wisconsin), sediment (Georgia),
and sand (Florida) were 19,300 (Kd = 236; organic matter, 0.71%), 20,900 (Kd = 217;
organic matter, 0.60%), 44,700 (Kd = 401; organic matter, 0.91%), and 60,900 (Kd = 140;
organic matter, 0.13%), respectively(1). The Kd for permethrin
was measured to be 400 on a red earth soil from Australia with an organic matter content
of 1.09%(2); the Koc was about 63,100(SRC). According to a classification scheme(3), these
Koc values suggest that permethrin is expected
to be immobile in soil(SRC). The distribution coefficients (Kd) for permethrin
on clean (i.e., without organic matter) montomorillonite, aluminum oxide and kaolinite
clay mineral surfaces were 61, 41, and 5 ml/g, respectively(4).
Volatilization from Water/Soil:
The Henry's Law constant for permethrin is
estimated as 1.87X10-6 atm-cu m/mole(SRC) based upon its vapor pressure, 2.18X10-8 mm
Hg(1), and water solubility, 6.0X10-3 mg/l(1). This Henry's Law constant indicates that permethrin is expected to volatilize from water
surfaces(2). Based on this Henry's Law constant, the volatilization half-life from a model
river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 26
days(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec,
wind velocity of 0.5 m/sec)(2) is estimated as 289 days(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 is 336
years if adsorption is considered(3). Permethrin's
estimated Henry's Law constant(1) indicates that volatilization from moist soil surfaces
may occur(SRC). However, volatilization from soil surfaces is expected to be attenuated by
adsorption to soil(SRC). Permethrin is not
expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).
Environmental Water Concentrations:
SURFACE WATER: As part of the National Drinking Water Contaminant Occurrence Database
(NDOD), permethrin was detected in 3 of 73
ambient spring water samples at an avg concn for positive samples of 0.0133 ug/l (max,
0.02; min, 0.01)(1); permethrin was also
detected in 24 of 12,253 other ambient surface water samples at an avg concn for positive
samples of 0.0137 ug/l (max, 0.03; min, 0.005)(1). Permethrin
was detected 6 hrs post-application at concns of 17 and 18 ng/l in 2 of 6 samples from a
creek approximately 60-100 m from a potato field where permethrin
was applied via aerial spraying(2). In 1996, permethrin
concn in surface waters from agricultural areas in Thailand was 2.81 ug/l(3). The
percentage of freshwater samples in England and Wales (UK) with concns of permethrin exceeding 0.01 ug/l in 1992 and 1993 were
6% of 816 samples(4).
GROUNDWATER: As part of the National Drinking Water Contaminant Occurrence Database
(NDOD), permethrin was detected in 3 of 5,728
ambient groundwater samples at an avg concn of 0.011 ug/l (max, 0.02; min, 0.006)(1).
Sediment/Soil Concentrations:
SOIL: Permethrin was detected in the
hydrosoil of a model outdoor pond at a concn of 1 ug/kg one year after treatment with 15
ug/l permethrin(1). Permethrin
was detected 30 days post-application at a concn of 10 ug/kg in 1 of 3 sediment samples
from a creek approximately 60-100 m from a potato field where permethrin
was applied via aerial spraying(2). Between 1996-1997, the concn of permethrin
in soil samples from cultivated areas in Thailand ranged from 62.41 to 1,178.40 ug/kg (24
samples)(3). The avg concn of permethrin in the
soil collected from 49 agrichemical facilities located throughout Illinois was 190 ug/kg
(range, 11 to 4.22X10+5 ug/kg)(4).
Atmospheric Concentrations:
URBAN: The mean concn of permethrin residues
in air particulates after use of the pesticide in the Muna Valley region of Saudi Arabia
ranged from 6.35 to 15.67 ug/cu m(1).
INDOOR AIR: According to a pilot investigation of pesticides in 9 homes in
Jacksonville, FL during August of 1985, permethrin
was qualitatively detected in the outdoor air (porch or patio) of 2 homes(1). The concn of
cis- and trans-permethrin in household dust
ranged between 255- 2850 and 365-3850 ug/kg, respectively, for 4 of 7 NJ homes in 1985(2).
In 1993, permethrin was detected in the ambient
air of insecticide storage and office rooms of a commercial pest control building in North
Carolina at a mean concn of 0.45 ug/cu m(3).
Food Survey Values:
During October 1, 1981 and September 30, 1986, permethrin
was found in 309 U.S. agricultural commodity samples at a concn 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 concn >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 concn 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 concn >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 concn 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 concn
1.0-2.0 ppm(2). As part of the FDA Total Diet Study in 1992-1993, the max concn 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 avg
concn (weighted) in imported tomatoes was 0.03 ppm(3).
As part of the FDA Total Diet Study as of 1991(1), the concn (in ppm) of cis-permethrin was determined in the following food items:
ham (baked, 0.001); eggs (fried, 0.001); peanuts (dry roasted, 0.006); popcorn (popped in
oil, 0.007); rye bread (0.0099); peach (raw, 0.0107); cantaloupe (raw, 0.0045); sweet
cherries (raw, 0.022); prunes (dried, 0.002); spinach (boiled, 0.6283); collards (boiled,
0.3331); iceberg lettuce (raw, 0.0104); sauerkraut (canned, 0.0005); broccoli (boiled,
0.0047); celery (raw, 0.0113); asparagus (boiled, 0.0862); cauliflower (boiled, 0.004);
red tomato (raw, 0.0072); green beans (boiled, 0.005); green pepper (raw, 0.0332); radish
(raw, 0.001); meatloaf (homemade, 0.0006); butter (salted, 0.002); half/half cream
(0.0003); tomato catsup (0.0009); pumpkin pie (0.0024); chicken (strained/junior, 0.001);
vegetables and chicken (strained/junior, 0.001); green beans (strained/junior, 0.0035);
creamed spinach (strained/junior, 0.0372); peaches (strained/junior, 0.0185); pears
(strained/junior, 0.0013); fruit dessert/pudding (strained/junior, 0.0045); veal cutlet
(pan-cooked, 0.002); cracked wheat bread (0.0009); peach (canned, 0.0004); tomato
(stewed/canned, 0.0015); Brussels sprouts (boiled, 0.0154); mushrooms (raw, 0.0285);
turnip (boiled, 0.001); okra (boiled, 0.002); beef stroganoff (0.018); green peppers
(stuffed, 0.0138); tuna noddle casserole (0.0014); cheeseburger (fast-food, 0.005); taco
or tostada (carry-out, 0.0015); cheese pizza (carry-out, 0.0006); pepperoni pizza
(carry-out, 0.0006); beef chow mein (carry-out, 0.0016); split peas with vegetables and
ham (0.0008); squash (strained/junior, 0.0009).
During the 32 month period ending Dec 1991, permethrin
was found in domestic Canadian agricultural commodities conducted by surveillance
sampling, eg, apples (fresh; range, 0.1 to 2> ppm)(1); permethrin
was also found in imported Canadian agricultural commodities, eg, celery (fresh; range,
<0.5 to 0.5 ppm), lettuce (fresh; range, <0.05-0.5 ppm), pepper (fresh; range,
<0.05 ppm), and spinach (fresh; range <0.05-2.0)(1). During January 1, 1992 and
March 31, 1994, permethrin was found in domestic
Canadian agricultural commodities conducted by surveillance sampling, eg, apples (fresh;
range, 0.5-2> ppm), celery (fresh; range, 0.5-1.0 ppm), head lettuce (fresh; range,
0.50 to >2.0 ppm), and spinach (fresh; range, 0.10-0.50 ppm)(2); permethrin
was also found in imported Canadian agricultural commodities, eg, artichokes (fresh;
range, 2.0> ppm), beets (fresh; range, 0.1-0.5 ppm), celery (fresh; range, <0.05 to
>2.0 ppm), cucumbers (fresh; range, 0.1-0.5 ppm), head lettuce (fresh; range <0.05
to >2.0 ppm), pears (fresh; range, 0.05-0.5 ppm), peppers (fresh sweet; range <0.05
to >2.0), spinach (fresh; range, 0.50 to >2.0 ppm), and tomatoes (fresh; range,
<0.05-2.0 ppm)(2). As part of the Ministry of Agriculture of Egypt's Residue Monitoring
Program in 1995, the avg concn of permethrin was
0.79 mg/kg (1 sample) and 0.11 mg/kg (1 sample) in tomatoes and peaches, respectively(3).
As part of the Ministry of Agriculture of Belgium's Total Diet Study between 1991-1993, permethrin was detected in lettuce (avg, 0.048 ppm;
max 1.02 ppm; 3.6% of samples), peppers (avg, 0.078 ppm; max, 1.06 ppm; 0.8% of samples),
and Lamb's lettuce (avg, 0.037 ppm; max, 0.75 ppm; 3.0% of samples)(4).
Plant Concentrations:
In a 1986 field study, the avg permethrin
concn found on strawberry flowers or young fruit were 0.637, 0.463, 0.0142, 0.071, 0.039,
and 0.015 ppm at 0, 2, 4, 7, 11, and 18 days after treatment, respectively(1); the avg
concn in 1987 were 2.180, 0.090, 0.143, 0.083, 0.089, and 0.027 ppm at 0, 2, 4, 7, 11, and
18 days after treatment, respectively(1).
Fish/Seafood Concentrations:
Permethrin was not detected at concns greater
than 10 ug/kg in 182 fish taken from 2 creeks approximately 60-100 m from potato fields
where permethrin was applied via aerial
spraying(1).
Environmental Standards & Regulations:
FIFRA Requirements:
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 future use. Under this pesticide reregistration program, EPA examines health
and safety data for pesticide active ingredients initially registered before November 1,
1984, and determines whether they are eligible for reregistration. In addition, all
pesticides must meet the new safety standard of the Food Quality Protection Act of 1996.
Pesticides for which EPA had not issued Registration Standards prior to the effective date
of FIFRA, as amended in 1988, were divided into three lists based upon their potential for
human exposure and other factors, with List B containing pesticides of greater concern and
List D pesticides of less concern. 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.
Tolerances, to expire on November 15, 1997, are established for residues of the
insecticide permethrin
[93-phenoxyphenyl)methyl-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane carboxylate] in
or on the following raw agricultural commodity: Cottonseed.
Tolerances are established for residues of the insecticide permethrin
and the sum of its metabolites
[(3-phenoxyphenyl)methyl-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxy late)]
and the sum of its metabolites 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane carboxylic
acid (DCVA) and (3-phenoxyphenyl)methanol (3-PBA) in or on the following raw agricultural
commodities: alfalfa, fresh; alfalfa, hay; almonds; almond hulls; apples; asparagus;
avocados; broccoli; Brussels sprouts; cabbage; cauliflower; celery; cherries; corn,
fodder; corn, forage; corn grain (field and pop); corn, sweet (K + CWHR); garlic;
horseradish; kiwi fruit; lettuce (head); mushrooms; onions, dry bulb; peaches; pears;
pistachios; potatoes; soybeans; spinach; tomatoes; vegetables, cucurbit; walnuts; and
watercress.
Tolerances are established for residues of permethrin
and the sum total of its metabolites 3-(2,2-dichloroethenyl)-2,2-dimethyl cyclopropane
carboxylic acid (DCVA) and (3-phenoxyphenyl)methanol (3-PBA) and 3-phenoxybenzoic acid in
or on the following animal commodities: cattle, fat; cattle, meat; cattle, mbyp; eggs;
goats, fat; goats, meat; goats, mbyp; hogs, fat; hogs, meat; hogs, mbyp; horses, fat;
horses, meat; horses, mbyp; milk fat (reflecting 0.25 ppm in whole milk); poultry, fat;
poultry, meat; poultry, mbyp; sheep, fat; sheep, meat; and sheep, mbyp.
Tolerances with regional registration, as defined in section 180.1(n), are established
for residues of permethrin
[(3-phenoxyphenyl)methyl-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane carboxylate] and
the sum of its metabolites 3-(2,2-dichloroethenyl)-(2,2-dimethylcyclopropane carboxylic
acid (DCVA) and (3-phenoxyphenyl)methanol (3-PBA) in or on the following raw agricultural
commodities: collards; papayas; turnip greens; and turnip roots.
Acceptable Daily Intakes:
OPP RfD= 0.05 mg/kg; EPA RfD= 0.05 mg/kg;
FAO/WHO ADI: 0.05 mg/kg bw
State Drinking Water Guidelines:
(FL) FLORIDA 350 ug/l
Allowable Tolerances:
Tolerances, to expire on November 15, 1997, are established for residues of the
insecticide permethrin
[93-phenoxyphenyl)methyl-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane carboxylate] in
or on the following raw agricultural commodity: Cottonseed: 0.5 ppm.
Tolerances are established for residues of the insecticide permethrin
and the sum of its metabolites
[(3-phenoxyphenyl)methyl-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxy late)]
and the sum of its metabolites 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane carboxylic
acid (DCVA) and (3-phenoxyphenyl)methanol (3-PBA) in or on the following raw agricultural
commodities: alfalfa, fresh, 25.0 ppm; alfalfa, hay, 55.0 ppm; almonds, 0.2 ppm; almond
hulls, 20.0 ppm; apples, 0.05 ppm; asparagus, 1.0 ppm; avocados, 1.0 ppm; broccoli, 1.0
ppm; Brussels sprouts, 1.0 ppm; cabbage, 6.0 ppm; cauliflower, 1.0 ppm; celery, 5.0 ppm;
cherries, 3.0 ppm; corn, fodder, 60 ppm; corn, forage, 60 ppm; corn grain (field and pop),
0.05 ppm; corn, sweet (K + CWHR), 0.1 ppm; garlic, 0.1 ppm; horseradish, 1.0 ppm; kiwi
fruit, 2.0 ppm; lettuce (head), 20.0 ppm; mushrooms, 6.0 ppm; onions, dry bulb, 0.1 ppm;
peaches, 5.0 ppm; pears, 3.0 ppm; pistachios, 0.1 ppm; potatoes, 0.05 ppm; soybeans, 0.05
ppm; spinach, 20.0 ppm; tomatoes, 2.0 ppm; vegetables, cucurbit, 3.0 ppm; walnuts, 0.05
ppm; and watercress, 5.0 ppm.
Tolerances are established for residues of permethrin
and the sum total of its metabolites 3-(2,2-dichloroethenyl)-2,2-dimethyl cyclopropane
carboxylic acid (DCVA) and (3-phenoxyphenyl)methanol (3-PBA) and 3-phenoxybenzoic acid in
or on the following animal commodities: cattle, fat, 3.0 ppm; cattle, meat, 0.25 ppm;
cattle, mbyp, 2.0 ppm; eggs, 1.0 ppm; goats, fat, 3.0 ppm; goats, meat, 0.25 ppm; goats,
mbyp, 2.0 ppm; hogs, fat, 3.0 ppm; hogs, meat, 0.25 ppm; hogs, mbyp, 3.0 ppm; horses, fat,
3.0 ppm; horses, meat, 0.25 ppm; horses, mbyp, 2.0 ppm; milk fat (reflecting 0.25 ppm in
whole milk), 6.25 ppm: poultry, fat, 0.15 ppm; poultry, meat, 0.05 ppm; poultry, mbyp,
0.25 ppm; sheep, fat, 3.0 ppm; sheep, meat, 0.25 ppm; and sheep, mbyp, 2.0 ppm.
Tolerances with regional registration, as defined in section 180.1(n), are established
for residues of permethrin
[(3-phenoxyphenyl)methyl-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane carboxylate] and
the sum of its metabolites 3-(2,2-dichloroethenyl)-(2,2-dimethylcyclopropane carboxylic
acid (DCVA) and (3-phenoxyphenyl)methanol (3-PBA) in or on the following raw agricultural
commodities: collards, 20 ppm; papayas, 1.0 ppm; turnip greens, 20 ppm; and turnip roots,
1 ppm.
Chemical/Physical Properties:
Molecular Formula:
C21-H20-Cl2-O3
Molecular Weight:
391.29
Color/Form:
Water white to pale yellow; colorless crystals to a viscous liquid
Boiling Point:
200 deg C at 0.1 mmHg; >290 deg C at 760 mmHg
Melting Point:
34-35 deg C
Corrosivity:
Does not corrode aluminum
Density/Specific Gravity:
1.19 - 1.27 @ 20 deg C
Octanol/Water Partition Coefficient:
log Kow= 6.50
Solubilities:
In xylene and hexane >1000, methanol 258 (all in g/kg at 25 deg C)
Soluble in most organic solvents except ethylene glycol.
In water, 6.00X10-3 mg/ml @ 20 deg C.
Vapor Pressure:
2.18X10-8 mm Hg @ 25 deg C
Other Chemical/Physical Properties:
Vapor pressure (pure): 2.5 mPa (cis), 1.5 mPa (trans)
Mixture of approx 60% trans- and 40% cis-isomers; colorless crystals to a pale yellow
viscous liquid; mp: ca 35 deg C; bp: 220 deg C at 0.05 mm Hg; sp gr: 1.190-1.272 at 20 deg
C/4 deg C; vapor pressure: < 1X10-6 mm Hg at 50 deg C; solubility in water: < 1 ppm;
sol or miscible with organic solvents except ethylene glycol. /Technical permethrin/
MP: cis-isomers, 63-65 deg C; trans-isomers, 44-47 deg C
Stable to heat (> 2 yrs at 50 deg C), more stable in acid than alkaline media with
optimum stability ca. pH 4.
Chemical Safety & Handling:
Skin, Eye and Respiratory Irritations:
Mild irritant to skin and eyes. /Technical permethrin/
Immediately irritating to the eye. /Pyrethrins/
The chief effect from exposure ... is skin rash particularly on moist areas of the
skin. ... May irritate the eyes. /Pyrethroids/
Fire Fighting Procedures:
Use carbon dioxide, foam, or dry chemical /on fires involving pyrethroids/. /Pyrethrum/
Fire-fighting: Self-contained breathing apparatus with a full facepiece operated in
pressure-demand or other positive-pressure mode. /Pyrethrum/
Hazardous Decomposition:
When heated to decomp it emits toxic fumes of /hydrogen chloride/.
Protective Equipment & Clothing:
Employees should be provided with and required to use dust- and splash-proof safety
goggles where /pyrethroids/ ... may contact the eyes. /Pyrethroids/
Employees should be provided with and be required to use impervious clothing, gloves,
and face shields (eight-inch minimum). /Pyrethroids/
Wear appropriate equipment to prevent: Repeated or prolonged skin contact. /Pyrethrum
and pyrethrins/
Wear eye protection to prevent: Reasonable probability of eye contact. /Pyrethrins/
Recommendations for respirator selection. Max concn for use: 50 mg/cu m: Respirator
Classes: Any chemical cartridge respirator with organic vapor cartridge(s) in combination
with a dust, mist, and fume filter. May require eye protection. Any supplied-air
respirator. May require eye protection. Any self-contained breathing apparatus. May
require eye protection. /Pyrethrins/
Recommendations for respirator selection. Max concn for use: 125 mg/cu m: Respirator
Classes: Any supplied-air respirator operated in a continuous flow mode. May require eye
protection. Any powered, air-purifying respirator with organic vapor cartridge(s) in
combination with a dust, mist, and fume filter. May require eye protection. /Pyrethrins/
Recommendations for respirator selection. Max concn for use: 250 mg/cu m: Respirator
Classes: Any chemical cartridge respirator with a full facepiece and organic vapor
cartridge(s) in combination with a high-efficiency particulate filter. Any self-contained
breathing apparatus with a full facepiece. Any supplied-air respirator with a full
facepiece. Any powered, air-purifying respirator with a tight-fitting facepiece and
organic vapor cartridge(s) in combination with a high-efficiency particulate filter. May
require eye protection. /Pyrethrins/
Recommendations for respirator selection. Max concn for use: 5,000 mg/cu m: Respirator
Class: Any supplied-air respirator with a full facepiece and operated in a pressure-demand
or other positive pressure mode. /Pyrethrins/
Recommendations for respirator selection. Condition: Emergency or planned entry into
unknown concn or IDLH conditions: Respirator Classes: Any self-contained breathing
apparatus that has a full facepiece and is operated in a pressure-demand or other positive
pressure mode. Any supplied-air respirator with a full face piece and operated in
pressure-demand or other positive pressure mode in combination with an auxiliary
self-contained breathing apparatus operated in pressure-demand or other positive pressure
mode. /Pyrethrins/
Recommendations for respirator selection. Condition: Escape from suddenly occurring
respiratory hazards: Respirator Classes: Any air-purifying, full-facepiece respirator (gas
mask) with a chin-style, front- or back-mounted organic vapor canister having a
high-efficiency particulate filter. Any appropriate escape-type, self-contained breathing
apparatus. /Pyrethrins/
Preventive Measures:
Skin that becomes contaminated with /pyrethrum/ should be promptly washed or showered
with soap or mild detergent and water. /Pyrethrum/
Clothing contaminated with /pyrethrum/ should be placed in closed containers for
storage until provision is made for the removal of /pyrethrum/ from the clothing.
/Pyrethrum/
Respirators may be used when engineering and work practice controls are not technically
feasible, when such controls are in the process of being installed, or when they fail or
need to be supplemented. Respirators may also be used for operations which require entry
into tanks or closed vessels, and in emergency situations. /Pyrethrum/
Employees who handle /pyrethrum/ ... should wash their hands thoroughly with soap or
mild detergent and water before eating, smoking, or using toilet facilities. /Pyrethrum/
Avoid contact with skin. Keep out of any body of water. Do not contaminate water by
cleaning of equipment or disposal of waste. Do not reuse empty container. Destroy it by
perforating or crushing. /Pyrethrum/
Contact lenses should not be worn when working with this chemical. /Pyrethrins/
Workers should wash: Promptly when skin becomes contaminated. /Pyrethrins/
Work clothing should be changed daily: If it is reasonably probable that the clothing
may be contaminated. /Pyrethrins/
Remove clothing: Promptly if it is non-impervious clothing that becomes contaminated.
/Pyrethrins/
SRP: The scientific literature for the use of contact lenses in industry is
conflicting. The benefit 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.
Stability/Shelf Life:
Stable to heat (> or = 2 yr at 50 deg C), more stable in acid than alkaline media
with optimum stability ca. pH 4; some photochemical degradation has been observed in
laboratory studies but field data indicate this does not adversely affect biological
performances.
Pyrethrins ... /are/ stable for long periods in water-based aerosols where ...
emulsifiers give neutral water systems. /Pyrethrins/
Storage Conditions:
Pyrethrins with piperonyl butoxide topical preparations should be stored in well-closed
containers at a temperature less than 40 deg C, preferably between 15-30 deg C.
/Pyrethrins/
Disposal Methods:
SRP: At the time of review, criteria for land treatment or burial (sanitary landfill)
disposal practices are subject to significant revision. Prior to implementing land
disposal of waste residue (including waste sludge), consult with environmental regulatory
agencies for guidance on acceptable disposal practices.
Incineration would be an effective disposal procedure where permitted. If an efficient
incinerator is not available, the product should be mixed with large amounts of
combustible material and contact with the smoke should be avoided. /Pyrethrin products/
Occupational Exposure Standards:
Manufacturing/Use Information:
Major Uses:
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./
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.
Nematocide; acaricide; insecticide
A contact insecticide effective against a broad range of pests. ... it is effective as
a wood preservative ...
Tick repellent
MEDICATION
MEDICATION (VET)
Manufacturers:
AstraZeneca LP, Zeneca Ag Products, 725 Chesterbrook Blvd, Wayne, PA 19087, (800)
237-8898; Production site: Cold Creek, AL 36512
FMC Corp., Agricultural Products Group, 200 E. Randolph Dr., Chicago, IL 60601, (312)
681-6000; Production site: Baltimore, MD 21226
Methods of Manufacturing:
3-Phenoxybenzy alcohol +
(1RS)-cis/trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboylic acid
(esterification)
General Manufacturing Information:
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.
Compatible with many common insecticides and fungicides.
Mixing with calcium nitrate is not recommended.
/Pyrethroids/ are modern synthetic insecticides similar chemically to natural
pyrethrins, but modified to increase stability in the natural environment. /Pyrethroids/
Formulations/Preparations:
USEPA/OPP Pesticide Code 109701; Trade Names: Permanone 10, Ambush.
Permanone 40, pounce, Matadan, NRDC 143, PP 557,
Ectiban, Indothrin, Pramex,
AI-29158, Diffusil H, Anomethrin N, Kavil, Perigen.
Emulsifiable concentrate; wettable powder; ULV liquid; fumigant; aerosol; dustable
powder; water-dispersible granules.
It is used as a broad-spectrum insecticide in a variety of formulations. The cis/trans
ratio varies depending on conditions of manufacture and can also vary with time due to
differential rates of hydrolysis and photolysis. A common ratio is 40:60 for agricultural
use, with veterinary preparations having lower ratios.
Mixtures (permethrin +) dimethoate;
pyrethrins; malathion; tetramethrin; heptenophos; bioallethrin + piperonyl butoxide;
primiphos-methyl; chloropyrifos-methyl+pyrethrins; bioallethrins S-cyclopentenyl isomer;
bioallethrin S-cyclopentenyl isomer + piperonyl butoxide.
Premixes: Pyra Perm (+ pyrethrins), Tetra Perm (+ tetramethrin), Per Super (+
S-bioallethrin), Tennin (+ tetramethrin), Chinetrin (+ piperonyl butoxide + tetrametrhin),
Killout (+ piperonyl butoxide + tetramethrin), Mobeesol (+ piperonyl butoxide +
tetramethrin) Duracide P, Super Duracide P (+ piperonyl butoxide + tetramethrin), Permethrin K (+ fenitrothion), Phinoco-T22 (+
piperonyl butoxide + tetramethrin)
Consumption Patterns:
In 1992, the estimated agricultural use of permethrin
in the United States was about 4,560 metric tons.
Laboratory Methods:
Analytic Laboratory Methods:
AOAC Method 986.03. Permethrin in Pesticide
Formulations by Gas Chromatography. Detection limit unspecified.
... Liquid chromatography method has been developed to quantitate pyrethrins in
pesticide formulations. ... Detection was monitored at 240 nm. ... Percent coefficients of
variation ranged from 1.39 to 9.68 with the majority less than 5.00. ... /Pyrethrins/
Pyrethrins were detected in soils by gas chromatography after extraction with hexane.
/Pyrethrins/
Low level pyrethrin formulations are extracted with tetrahydrofuran and determined via
capillary gas chromatography with electron capture detection. ... Analysis of 5
formulations gave an average standard deviation of 3.3%. /Pyrethrins/
Special References:
Special Reports:
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.
Miyamoto J; Environ Health Perspect 14: 15-28 (1976). Degradation, metabolism, and
toxicity of synthetic pyrethroids.
Miyamoto J, et al; Pure Appl Chem 53: 1967-2022 (1981). The chemistry, metabolism, and
residue analysis of synthetic pyrethroids.
Hutson DH; Progress in Drug Metabolism 3: 215-252 (1979). The metabolic fate of
synthetic pyrethroid insecticides in mammals.
Gammon DW; Fundam Appl Toxicol (5) 1: 9-23 (1985). Correlations between in vitro and in
vivo mechanisms of pyrethroid insecticide action.
Casida JE et al; Ann Rev Pharmacol Toxicol 23: 413-38 (1983). The mechanisms of
selective action of pyrethroid insecticide are discussed.
Papadopoulou-Mourkidou E; Residue Rev 89: 179-208 (1983). A review with many references
on analysis of allethrin & other pyrethroid insecticides.
Synonyms and Identifiers:
Synonyms:
S 3151
**PEER REVIEWED**
Ambush
**PEER REVIEWED**
biopermethrin (trans isomer)
**PEER REVIEWED**
BW 21-Z
**PEER REVIEWED**
cispermethrin (cis isomer)
**PEER REVIEWED**
Coopex
**PEER REVIEWED**
Corsair
**PEER REVIEWED**
Cosair
**PEER REVIEWED**
3-(2,2-Dichloroethenyl)-2,2-dimethylcyclopropanecarboxylic acid (3-
phenoxyphenyl)methyl ester
**PEER REVIEWED**
Dragnet
**PEER REVIEWED**
Dragon
**PEER REVIEWED**
Ectiban
**PEER REVIEWED**
Eksmin
**PEER REVIEWED**
Pesticide Code 109701
**PEER REVIEWED**
EXMIN
**PEER REVIEWED**
Expar
**PEER REVIEWED**
FMC 33297
**PEER REVIEWED**
FMC 41655
**PEER REVIEWED**
ICI-PP 557
**PEER REVIEWED**
Imperator
**PEER REVIEWED**
Kafil
**PEER REVIEWED**
Kestrel
**PEER REVIEWED**
NDRC 143
**PEER REVIEWED**
NIA 33297
**PEER REVIEWED**
Nix
**PEER REVIEWED**
NRDC 143
**PEER REVIEWED**
Outflank
**PEER REVIEWED**
OUTFLANK STOCKADE
**PEER REVIEWED**
Perigen
**PEER REVIEWED**
Permasect
**PEER REVIEWED**
Permethrine (French spelling)
**PEER REVIEWED**
Permit
**PEER REVIEWED**
Perthrine
**PEER REVIEWED**
m-Phenoxybenzyl(+1)-cis,trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-
carboxylate
**PEER REVIEWED**
3-Phenoxybenzyl (1RS)-cis,trans-3-(2,2-dichlorvinyl)-2,2-dimethylcyclopropane-
carboxylate
**PEER REVIEWED**
3-(Phenoxyphenyl)methyl (+-)-cis,trans-3-(2,2-dichloroethenyl)-2,2-
dimethylcyclopropanecarboxylate
**PEER REVIEWED**
(3-Phenoxyphenyl)methyl 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane- carboxylate
**PEER REVIEWED**
(3-phenoxyphenyl)methyl-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane- carboxylate
**PEER REVIEWED**
Picket
**PEER REVIEWED**
Pounce
**PEER REVIEWED**
PP 557
**PEER REVIEWED**
Pramex
**PEER REVIEWED**
Pynosect
**PEER REVIEWED**
Quamlin
**PEER REVIEWED**
Ridect Pour-On
**PEER REVIEWED**
SBP 1513
**PEER REVIEWED**
Stomoxin
**PEER REVIEWED**
Talcord
**PEER REVIEWED**
WL 43479
**PEER REVIEWED**
Formulations/Preparations:
USEPA/OPP Pesticide Code 109701; Trade Names: Permanone 10, Ambush.
Permanone 40, pounce, Matadan, NRDC 143, PP 557,
Ectiban, Indothrin, Pramex,
AI-29158, Diffusil H, Anomethrin N, Kavil, Perigen.
Emulsifiable concentrate; wettable powder; ULV liquid; fumigant; aerosol; dustable
powder; water-dispersible granules.
It is used as a broad-spectrum insecticide in a variety of formulations. The cis/trans
ratio varies depending on conditions of manufacture and can also vary with time due to
differential rates of hydrolysis and photolysis. A common ratio is 40:60 for agricultural
use, with veterinary preparations having lower ratios.
Mixtures (permethrin +) dimethoate;
pyrethrins; malathion; tetramethrin; heptenophos; bioallethrin + piperonyl butoxide;
primiphos-methyl; chloropyrifos-methyl+pyrethrins; bioallethrins S-cyclopentenyl isomer;
bioallethrin S-cyclopentenyl isomer + piperonyl butoxide.
Premixes: Pyra Perm (+ pyrethrins), Tetra Perm (+ tetramethrin), Per Super (+
S-bioallethrin), Tennin (+ tetramethrin), Chinetrin (+ piperonyl butoxide + tetrametrhin),
Killout (+ piperonyl butoxide + tetramethrin), Mobeesol (+ piperonyl butoxide +
tetramethrin) Duracide P, Super Duracide P (+ piperonyl butoxide + tetramethrin), Permethrin K (+ fenitrothion), Phinoco-T22 (+
piperonyl butoxide + tetramethrin)
Administrative Information:
Hazardous Substances Databank Number: 6790
Last Revision Date: 20011010
Last Review Date: Reviewed by SRP on 5/10/2001
Update History:
Complete Update on 10/10/2001, 60 fields added/edited/deleted.
Field Update on 08/08/2001, 1 field added/edited/deleted.
Field Update on 05/16/2001, 1 field added/edited/deleted.
Complete Update on 09/12/2000, 1 field added/edited/deleted.
Complete Update on 06/12/2000, 1 field added/edited/deleted.
Complete Update on 03/13/2000, 1 field added/edited/deleted.
Complete Update on 02/08/2000, 1 field added/edited/deleted.
Complete Update on 02/02/2000, 1 field added/edited/deleted.
Complete Update on 09/21/1999, 1 field added/edited/deleted.
Complete Update on 08/27/1999, 1 field added/edited/deleted.
Complete Update on 06/08/1999, 6 fields added/edited/deleted.
Field Update on 03/23/1999, 1 field added/edited/deleted.
Field Update on 06/03/1998, 1 field added/edited/deleted.
Field Update on 11/01/1997, 1 field added/edited/deleted.
Field Update on 05/09/1997, 1 field added/edited/deleted.
Complete Update on 03/17/1997, 2 fields added/edited/deleted.
Complete Update on 02/28/1997, 1 field added/edited/deleted.
Complete Update on 10/20/1996, 1 field added/edited/deleted.
Complete Update on 09/06/1996, 1 field added/edited/deleted.
Complete Update on 05/14/1996, 1 field added/edited/deleted.
Complete Update on 02/01/1996, 1 field added/edited/deleted.
Complete Update on 08/21/1995, 1 field added/edited/deleted.
Complete Update on 06/16/1994, 1 field added/edited/deleted.
Complete Update on 03/01/1994, 70 fields added/edited/deleted.
Record Length: 200506