RESMETHRIN
Human Health Effects:
Human Toxicity Excerpts:
Although the resmethrins have been used for many years, no data have been reported on
their toxicity for human beings.
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/
Contact allergy from pyrethroids ... has not been observed. /Pyrethroids/
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, and cypermethrin) may cause a transient itching and/or burning sensation in
exposed human skin. /Synthetic pyrethroids/
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, and even laryngeal mucosal edema. Localized
reaction of the lower respiratory tract include cough, shortness of breath, wheezing, and
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/
Skin, Eye and Respiratory Irritations:
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.
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/
Populations at Special Risk:
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. ... /Pyrethroids/
Probable Routes of Human Exposure:
NIOSH (NOES Survey 1981-1983) has statistically estimated that 27,596 workers (3,998 of
these are female) are potentially exposed to resmethrin
in the US(1). Occupational exposure to resmethrin
may occur through inhalation and dermal contact with this compound at workplaces where resmethrin is produced or used(SRC). Resmethrin
was detected in indoor air of 10 commercial pest control firms in North Carolina at concns
of 0.31-5.22 ug/cu m(2). Since resmethrin is a
widely used insecticide that can be employed for the control of a variety of insects,
mosquitos, and in pet sprays and shampoos, the general population may be exposed to
resmethrind through use of insecticides containing this compound(SRC). Resmethrin
was identified, but not quantified, in households after application from spray cans, pet
shampoos and hand-pumped broadcast sprayers(3).
Average Daily Intake:
Using the Total Exposure Assessment Methodology (TEAM), air samples in residential
households were collected over 24-hr periods in indoor, outdoor and personal air in two
areas (Jacksonville, FL and Springfield/Chicopee, MA)(1); based upon air sample
detections, the annual avg daily concn to resmethrin
was estimated to be 0.1 ng/cu m in Jacksonville, FL(1); resmethrin
was not detected in the MA area samplings(1).
Emergency Medical Treatment:
Emergency Medical Treatment:
| EMT Copyright Disclaimer: |
| Portions of the POISINDEX(R) database are provided here for general
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/
Basic treatment: . Establish a patent airway. Suction if necessary. Watch for signs of
respiratory insufficiency and assist ventilations if necessary. Administer oxygen by
nonrebreather mask at 10 to 15 L/min. Anticipate seizures and treat if necessary... . For
eye contamination, flush eyes immediately with water. Irrigate each eye continuously with
normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and
administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a
strong gag reflex, and does not drool. Administer activated charcoal ... . /Pyrethrins,
pyrethroids, and related compounds/
Advanced treatment: Consider orotracheal or nasotracheal intubation for air way control
in the patient who is unconscious. Monitor cardiac rhythm and treat arrhythmias if
necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/.
Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid
overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride
to assist eye irrigation ... . /Pyrethrins, pyrethroids, and related compounds/
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/
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:
Non-Human Toxicity Excerpts:
ACUTE APPLICATION TO RABBIT SKIN FAILED TO IRRITATE OR CAUSE ACNEFORM REACTIONS. COTTON
SATEEN CLOTH IMPREGNATED WITH RESMETHRIN
PRODUCED ONLY SLIGHT IRRITANT EFFECT IN 24-DAY WEAR TEST WITH RABBITS. DAILY INGESTION OF
1500 MG/KG WAS NEEDED TO KILL SPRAGUE-DAWLEY OR LONG EVANS RATS IN 14 & 90 DAY FEEDING
STUDIES. DAILY IV ADMIN OF 25 MG/KG FOR 15 DAYS IN BEAGLE DOGS PRODUCED NO TOXIC EFFECTS,
OR COMPOUND-RELATED ENZYME CHANGES.
IN ACUTE TOXICITY STUDIES RESMETHRIN IN CORN
OIL WAS ADMIN INTRAGASTRICALLY, 0.1 MG/10 G BODY WT & 0.5-1 ML/100 G BODY WT TO DD
STRAIN MICE & SPRAGUE-DAWLEY (SD) RATS, RESPECTIVELY. HYPERSENSITIVITY, TREMORS &
ATAXIA /WERE OBSERVED/.
Toxic to bees.
RATS AND MICE WERE EXPOSED /VIA INHALATION/ FOR 4 HR TO (+)-TRANS,CIS-RESMETHRIN.
NO DEATHS OCCURRED. SYMPTOMS WERE ATAXIA AND URINARY INCONTINENCE. MINIMUM TOXIC DOSE 400
MG/CU M. 500, 1500, AND 5000 PPM WERE ADMIN ORALLY TO SD STRAIN RATS. DURATION OF STUDY 24
WK. AT 5000 PPM, LIVER WT AND ALANINE PHOSPHATASE INCREASED.
IN A HOST-MEDIATED ASSAY USING SALMONELLA TYPHIMURIUM STRAIN G46, RESMETHRIN
DID NOT INCR REVERSION FREQUENCY.
... Resmethrin ... was not found to be
mutagenic in (a) Salmonella typhimurium strains TA100 or TA98 in the presence or absence
of a rat liver activation system using the plate incorporation assay and fluctuation tests
or (b) V79 Chinese hamster cells in the presence or absence of hepatocytes. ...
Resmethrin was applied twice a week for 3
weeks to the shaved skin of 4 groups of 10 male New Zealand White rabbits. Cotton cloth
treated with resmethrin at 0.247 mg/cu m was
applied over 1 ml of liquid (imitating sweat) to rabbits in the first group. In the second
group, cotton cloth treated with resmethrin was
applied without the sweat, and in the third group, the cotton cloth was fixed to skin that
had been pretreated with 10 g of technical grade resmethrin.
In the fourth group, untreated cotton cloth was fixed over skin pretreated with pyrax
powder containing 1% resmethrin at the rate of 1
g/kg of body weight. The 3 control groups received cotton cloth treated with acetone,
cotton cloth treated with acetone over 1 ml of the sweat, and untreated cotton cloth over
1 g pyrax powder/kg, respectively. No significant changes were noted, on day 24 of the
test in rabbit body weights and organ-to-body weight ratios of liver, lung, kidney,
testis, and spleen. Average dermal irritation scores for resmethrin-treated
rabbits were not significantly higher than those for the control groups and did not
increase during the test. No significant trends compared with the controls were seen in
clinical chemistry values (serum-glutamic oxaloacetic dehydrogenase, alkaline phosphatase,
blood-urea nitrogen) on days 5, 12, 19, and 24 of the test. There were no compound-related
lesions of the skin or any of the other tissues and organ examined at the termination of
the study.
When Sprague-Dawley or Long-Evans rats were fed resmethrin
in the diet at levels of up to 6000 mg/kg for 14 days, mortality was observed at the
highest dose level, and tremor and reduced body weight and food consumption were noted at
levels of 1500 mg/kg or more. The maximum no-observed-adverse-effect dietary level was 188
mg/kg for Long-Evans rats.
When Long-Evans rats were given resmethrin in
the diet at levels of up to 750 mg/kg (male) and up to 2400 mg/kg (female) for 90 days,
all females died at 2400 mg/kg and tremor and reduced body weight were noted at 750 mg/kg.
The maximum no-observed-adverse-effect dietary level was 75 mg/kg for both female and male
rats.
Technical resmethrin was administered via
inhalation to Wistar rats for 6 h/day on 5 days of each week, for a period of 90 days, at
nominal exposure levels of 0.1, 0.3, or 1.0 g/cu m. The non-observed-adverse-effect level
was at 0.1 g/cu m.
Dogs (males and females) were administered bioresmethrin at levels of up to 500 mg/kg
body weight for 90 days. A no-observed-adverse-effect level was observed of 80 mg/kg body
weight.
When rats were fed bioresmethrin in the diet at levels of up to 8000 mg/kg for 91 days,
body weight was reduced at the highest level, and was accompanied by changes in blood
chemistry indicating liver dysfunction. The no-observed-adverse-effect level in this study
was 400 mg/kg diet, which corresponds to 32.8 mg/kg body weight and 36.1 mg/kg body weight
for males and females, respectively.
Technical grade resmethrin was found to be a
slight irritant in rabbits in a 24 day dorsal/ventral rabbit ear test. Dermal irritation
was evident on both intact and abraded skin at 72 hr and up to7 days. Resmethrin
did not cause sensitization reactions in guinea-pigs, or photochemical irritation in New
Zealand White rabbits. Repeated daily applications of 0.1 g of the technical grade
compound to one ear of each of 5 New Zealand White rabbits were carried out for 30
consecutive days as well as applications of compound-impregnated cotton sateen cloth
(0.247 mg/sq cm) with artificial sweat for 24 days. In this study, resmethrin
did not produce acne-form dermatitis.
In order to better characterize the behavioural effects of pyrethroid insecticides,
comparisons were made of the effects of cismethrin and deltamethrin exposure on motor
activity and the acoustic startle response in male Long-Evans rat. Acute dose effect,
acute time course, and 30 day repeated-exposure determinations of 1 hr motor activity were
made using figure-eight mazes. The acoustic startle response to a 13 kHz, 120 dB, 40
msecond tone was measured at each of the three background white noise levels (50, 65, and
80 dB). Deltamethrin (0, 2, 4, 6, or 8 mg/kg) or cismethrin (0, 6, 12, 18, or 24 mg/kg)
was administered orally in 0.2 ml corn oil/kg. Both compounds produced similar
dose-dependent decreases in motor activity. The time course of onset and recovery for this
decreased activity was rapid (1-4 hr). No cumulative effects on motor activity were found
of a 30 day exposure to 2 mg deltamethrin/kg per day or 6 mg cismethrin/kg per day. The
effects of cismethrin and deltamethrin on the acoustic startle response differed.
Deltamethrin produced a dose-dependent decrease in amplitude and an increase in latency,
and cismethrin produced an increase in amplitude and no change in latency. The
differential effects of cismethrin (Type I pyrethroids) and deltamethrin (Type II
pyrethroids) on the acoustic startle response may be related to the contrasting effects
previously shown with neurophysiological and/or neurochemical techniques.
Pregnant New Zealand White Minnikin rabbits were given resmethrin
by oral intubaton at 0, 10, 30, or 100 mg/kg body weight per day on days 6-18 of
gestation. On day 29 of gestation, all animals were killed for examination. No teratogenic
effects were seen at dose levels up to and including 100 mg/kg.
Sprague-Dawley female albino rats were given resmethrin
in corn oil, by gavage, at dose levels of 0, 20, 40, or 80 mg/kg during the period of
major organogenesis (days 6-15 of gestation). Resmethrin
was not teratogenic in rats at levels up to, and including, 80 mg/kg. The
no-observed-adverse-effect level for fetotoxicity was 40 mg/kg.
The isolated rat neurohypophysis, which shows a calcium-dependent hormone release when
depolarized in vitro, was used as a model system to investigate the effects of the
pyrethroids deltamethrin and resmethrin on
mammalian nervous tissue. Both compounds inhibited neurohypophysical hormone release in
response to electrical stimulation, deltamethrin being more potent than resmethrin.
Deltamethrin reduced the hormone content of the neurohypophysis. Resmethrin
did not reduce stored hormone significantly and its effects on release were dose
dependent. They could be mimicked by raising the Na+ of the medium, but not by lowering te
Ca2+. Resmethrin did not have any effects on the
release of hormone following depolarization of the tissue with a raised K+. The results
are consistent with the suggestion that the compounds do not act on the
potential-dependent secretion process but rather on the mechanism linking depolarization
of the secretory terminals with the arrival of action potentials, possibly by interfering
with sodium-channel activation and inactivation.
Three groups of 30 pregnant Long-Evans rats were administered resmethrin
in the diet at concentrations of 0, 188, or 1500 mg/kg from day 6 to day 16 of gestation.
The dams showed tremors and decreased food and water consumption at 1500 mg/kg and 2 dams
died; the lower fetal weight seen at this dose and the resorption of embryos and fetuses
in 15 out of 30 dams were probably due to maternal toxicity. No gross abnormalities of
fetal skeletons and soft tissues were observed in the treated groups. Thus, the
consumption of resmethrin in ground feed was not
teratogenic at 188 and 1500 mg/kg.
When [1R, trans, cis]-resmethrin was
administered orally to female ICR mice (10, 30, or 100 mg/kg daily) and Sprague-Dawley
rats (10, 20, or 50 mg/kg daily) during the period of gestation, to examine maternal and
embryotoxic effects, no significant adverse effects, such as abortion, resorption of
fetuses or embryos, external or skeletal abnormalities of pups, and abnormalities in
growth or organ differentiation, were observed at any dose.
In a 3-generation study, Sprague-Dawley rats were fed resmethrin
in the diet at 0, 500, 800, or 1250 mg/kg. A slight increase in the number of pups cast
dead and a decrease in pup weights were noted at the 500 mg/kg level. A
no-observed-adverse-effect level of < 500 mg/kg was established for pups cast dead and
reduced pup weights at 21 days.
The influence of various pesticides on the humoral and cellular immune response to
fluorescein-labelled ovalbumin has been analysed. Resmethrin
was administered intragastrically in corn oil as a single dose (one half of LD50) before
primary immunization. Control groups included animals treated with corn oil alone, or
immunosuppressed with methotrexate. Booster immunizations and test bleedings were
scheduled to follow at weekly intervals. The cellular immune response was quantified by
redness and swelling, histological examination, and by differential temperature
measurements of the foot pads after antigen challenge. The concentration, binding
affinity, and heterogeneity of the serum antibody were determined by fluorescence
polarization measurements. Resmethrin gave an
early, sometimes very marked, stimulation of the cellular immune response.
Outbred albino mice /fed/ with 0, 250, 500, or 1000 mg resmethrin/kg
basal diet for an 85-week period. No oncogenicity was observed at any doses up to and
including 1000 mg/kg.
When Beagle dogs were administered 0, 10, 30, or 300 mg resmethrin/kg
body weight for 6 months, the no-observed-adverse-effect level was 10 mg/kg per day. On
day 57 of the study, the highest dose level was increased from 100 mg/kg per day to 300
mg/kg per day. Increased liver weights were noted at 30 mg/kg body weight per day.
Saccharomyces cerevisiae D4 and five strains of Salmonella typhimurium (TA1535, TA1537,
TA1538, TA98, and TA100) were used to evaluate the mutagenic potential of resmethrin. The compound was tested in the absence or
presence of liver microsomal enzyme preparations from rats pre-treated with Aroclor 1254. Resmethrin was not mutagenic to any of the indicator
organisms under both conditions.
When [1R, trans,cis]-resmethrin was fed to
Sprague-Dawley rats (male and female) at dietary levels of 500, 1500, or 5000 mg/kg for 24
weeks, toxic symptoms, such as tremors and decreased body weight, increased liver and
kidney weights and an increase in alkaline phosphatase activity were observed at 5000
mg/kg. The no-observed-adverse-effect level was 1500 mg/kg (77.7 mg/kg per day for males
and 86.6 mg/kg per day for females).
Resmethrin fed to Wistar rats at dosage
levels of 0, 500, 2500, or 5000 mg/kg in the basal diet over a 112-week period, was
determined not to be oncogenic up to, and including, 5000 mg/kg, which was the highest
dose tested. The no-observed-adverse-effect level of 500 mg/kg for toxic effects, was the
lowest effect level for hypertrophy of hepatocytes, which was not considered a definite
toxic response.
/From examination of/ species and structural variations affecting pyrethroid
neurotoxicity. ... /it was/ concluded that the mammalian nervous system, or at least the
brain, appears to lack sites sensitive to bioresmethrin and to a lesser extent to [1R,
trans]-permethrin, yet small structural changes restore the toxicity (e.g.,
[1R,trans]-ethano-resmethrin and [1R, cis]-resmethrin. The authors reported that birds and
mammals in general respond to cis- but not to trans-resmethrin
in contrast to insects, crustaceans, and fish, which are highly sensitive to both isomers.
Furthermore, common green lacewing larvae are very tolerant to pyrethroids, suggesting
possible involvement of nerve insensitivity in addition to detoxification in this species.
These examples of insensitivity may be associated with modified sites of action or perhaps
an increased stabilization of nerve membranes making them more resistant to
pyrethroid-induced excitation.
The neurological effects of four synthetic pyrethroids resmethrin,
permethrin, cypermethrin, and deltamethrin were investigated in the rat to establish
whether there is a correlation between the clinical-functional status of the animal and
peripheral nerve damage, as measured biochemically. Neuromuscular dysfunction was assessed
by means of the inclined plane test and peripheral nerve damage by reference to
b-glucuronidase and b-galactosidase activity increases in nerve tissue homogenates from
treated and control animals. A transient functional impairment was found in animals
treated with any one of the four pyrethroids tested and, in all cases, this was maximal at
the end of the 7-day dosing regimen (resmethrin
doses of 500-2000 mg/kg per day). Significant increases in b-glucuronidase and
b-galactosidase were found, 3-4 weeks after the start of dosing in the distal portion of
the sciatic/posterior tibial nerves of animals treated with permethrin, cypermethrin, or
deltamethrin; however, no changes were found in resmethrin
treated animals. Thus, it is concluded that there is no direct correlation between the
time-course of the neuromuscular dysfunction and the neurobiochemical changes. This
suggests that these pyrethroids have at least two distinct actions, a short-term
pharmacological effect and, at near-lethal dose levels, a more chornic neurotoxic effect
that results in sparse axonal nerve damage.
Toxic symptoms of resmethrin are like those
of other pyrethrins and include immediate irritability, tremors, coma and death.
Four pyrethroids, allethrin, resmethrin,
permethrin and fenvalerate, were tested for mutagenicity in bacterial reversion assay
systems with seven strains (TA1535, TA100, TA1538, TA98, TA1537, TA97 and TA104) of
Salmonella typhimurium. Our results show that three pyrethroids, namely resmethrin,
permethrin and fenvalerate, were not found to be mutagenic in Salmonella typhimurium in
the presence or absence of a rat liver activation system. Allethrin was found to be
mutagenic with TA100, TA104 and TA97 strains and required metabolic activation (S9 mix) in
order to show its activity, mainly with TA100 and TA104 strains.
Synthetic pyrethroids are neuropoisons acting on the axons in the peripheral and
central nervous systems by interacting with sodium channels in mammals and/or insects. A
single dose produces toxic signs in mammals, such as tremors, hyperexcitability,
salivation, choreoathetosis, and paralysis. ... At near-lethal dose levels, synthetic
pyrethroids cause transient changes in the nervous system, such as axonal swelling and/or
breaks and myelin degeneration in sciatic nerves. They are not considered to cause delayed
neurotoxicity of the kind induced by some organophosphorus compounds. /Synthetic
prethroids/
The /SRP: pyrethrins and pyrethrum/ are ... contact poisons that rapidly penetrate into
the nerve system and cause characteristic symptomatology in the insect. A phase of
exceptional excitation is followed by disturbance in coordination of movement, paralysis,
and finally death. The initial effect is of such rapid onset that within a few minutes the
insect is incapable of moving or flying away. This knockdown effect is attained by few
insecticides, particularly against flies. The dose necessary for knockdown is usually
insufficient to be lethal because the /SRP: pyrethrins and pyrethrum/ are rapidly
detoxified in the insect by enzymatic action, and some of them recover. ... Resmethrin ... has ... a weaker knockdown effect but a
much higher toxicity towards a variety of insects.
Synthetic pyrethroids have been shown to be toxic for fish, aquatic arthropods, and
honeybees in laboratory tests. But, in practical usage, no serious adverse effects have
been noticed because of the low rates of application and lack of persistence in the
environment. The toxicity of synthetic pyrethroids in birds and domestic animals is low.
/Synthetic pyrethroids/
Following absorption through the chitinous exoskeleton of arthropods, pyrethrins
stimulate the nervous system, apparently by competitively interfering with cationic
conductances in the lipid layer of nerve cells, thereby blocking nerve impulse
transmissions. Paralysis and death follow. /Pyrethrins/
Non-systemic insecticide with contact action. Causes paralysis initially, with death
occurring later. Has some acaricidal activity. /Pyrethrins/
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/
The type I pyrethroids /including resmethrin/
produce the simplest poisoning sydrome & 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,
incoordinated 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.
Non-Human Toxicity Values:
LD50 Rat oral 1400 mg/kg
LD50 Rat oral >2500 mg/kg
LD50 Rat percutaneous >3000 mg/kg
LD50 Rat (male) dermal 2500 mg/kg
LD50 Rat (female) dermal 2500 mg/kg
LD50 Rabbit dermal 2500 mg/kg
LC50 Rat inhalation >9490 mg/cu m/4 hr
LC50 Rat inhalation >12,000 mg/cu m/1 hr
LC50 Rabbit inhalation >12,000 mg/cu m/1 hr
LC50 Dog inhalation >420 mg/cu m/4 hr
LD50 Rat (Male) oral 1244 mg/kg
LD50 Rat (female) oral 1721 mg/kg
LD50 Rat (weanling, male) oral 1987 mg/kg
LD50 Mice (male) oral 690 mg/kg
LD50 Mice (female) oral 940 mg/kg
LD50 Rat dermal 3.0 g/kg
LD50 Rat subcutaneous >5 g/kg
LD50 Mouse oral 300 mg/kg
LD50 Mouse skin >5 g/kg
LD50 Mouse ip >1 g/kg
LD50 Mouse subcutaneous >2 g/kg
Ecotoxicity Values:
LC50 ONCORHYNCHUS KISUTCH (COHO SALMON) 1.8 UG/L/96 HR @ 18 DEG C (95% CONFIDENCE LIMIT
0.55-5.6 UG/L) WT 0.5 G /TECHNICAL MATERIAL, 84.5%/
LC50 SALVELINUS NAMAYCUSH (LAKE TROUT) 1.7 UG/L/96 HR @ 12 DEG C (95% CONFIDENCE LIMIT
1.1-2.5 UG/L) WT 0.7 G /TECHNICAL MATERIAL, 84.5%/
LC50 PIMEPHALES PROMELAS (FATHEAD MINNOW) 3.0 UG/L/96 HR @ 17 DEG C (95% CONFIDENCE
LIMIT 0.89-9.9 UG/L) WT 0.7 G /TECHNICAL MATERIAL, 84.5%/
LC50 ICTALURUS PUNCTATUS (CHANNEL CATFISH) 16.6 UG/L/96 HR @ 18 DEG C (95% CONFIDENCE
LIMIT 9.6-28.6 UG/L) WT 0.7 G /TECHNICAL MATERIAL, 84.5%/
LC50 LEPOMIS MACROCHIRUS (BLUEGILL) 1.7 UG/L/96 HR @ 18 DEG C (95% CONFIDENCE LIMIT
0.31-9.3 UG/L) WT 0.6 G /TECHNICAL MATERIAL, 84.5%/
LD50 California quail oral > 2000 mg/kg, 5-6 mo old male
LC50 Coho salmon > 150 ug/l/96 hr (static test); < 0.277 ug/l/96 hr (flow-through
test)
LC50 Steelhead trout 0.450 ug/l/96 hr (static test); 0.275 ug/l/96 hr (flow-through
test)
LC50 Bluegill 2.62 ug/l/96 hr (static test); 0.750 ug/l/96 hr (flow-through test)
LC50 Yellow perch 2.36 ug/l/96 hr (static test); 0.513 ug/l/96 hr (flow-through test)
LC50 Daphnia pulex 15000 ug/l/3 hr (static @ 25 deg C) /Technical/
LC50 Moina macrocopa 14000 ug/l/3 hr (static @ 25 deg C) /Technical/
LC50 Sigara substriate (Size = 0.59 cm: 6.1 mg) 2 ug/l/48 hr (static @ 25 deg C)
/Technical/
LC50 Micronecta sedula (size = 0.32 cm: 1.8 mg) 3.3 ug/l/48 hr (static @ 25 deg C)
/Technical/
LC50 Cloeon dipterum (Size = 0.93; 5.6 mg) 4.5 ug/l/48 hr (static @ 25 deg C)
/Technical/
LC50 Orthetrum albistylum speciosum (Size = 2.3 cm; 0.62 g) 7.3 ug/l/48 hr (static @ 25
deg C) /Technical/
LC50 Eretes stricticus (Size = 1.5 cm; 0.2 g) 25 ug/l/48 hr (static @ 25 deg C)
/Technical/
Sympetrum frequens (Size = 2.1 cm; 0.56 g) 10 ug/l/48 hr (static @ 25 deg C)
/Technical/
LC50 (Cyprinus carpio) Carp 44 ug/l/48 hr (static system) /Technical/
LC50 Oryzias latipes (killifish), adult 300 ug/l/48 hr (statis system) /Technical/
Metabolism/Pharmacokinetics:
Metabolism/Metabolites:
THE TRANS-ISOMERS AS RESMETHRIN ARE
METABOLIZED MAINLY THROUGH HYDROLYSIS OF ESTER LINKAGE WITH SUBSEQUENT OXIDATION &/OR
CONJUGATION OF COMPONENT ALCOHOL & ACID MOIETIES. 1/3 OF ACID-DERIVED METAB OF
(+)-TRANS-RESMETHRIN ADMIN TO RATS WERE
CHARACTERIZED & AMONG THEM CIS-HYDROXYMETHYL CHRYSANTHEMUMIC ACID &
CIS-CHRYSANTHEMUM DICARBOXYLIC ACID WERE IDENTIFIED. (+)-CIS-RESMETHRIN
YIELDED TRANS ISOMERS OF ACIDS.
Resmethrin isomers were metabolized in
microsome-NADPH systems to the extent of 95 to 98%. The extent to which trans- and
cis-isomers were metabolized differed. In the presence of NADPH, ester cleavage was much
greater with tetraethylpyrophosphate-treated microsomes. An oxidative ester cleavage
seemed to be most important with (-)-cis-resmethrin.
In the latter case, alcohol moieties released include unstable compounds and protein-bound
metabolites. Seventeen precent of the initial radiocarbon appeared in 11 ester metabolites
(not identified) of (+)-trans-resmethrin. These
were recovered only with tetraethylpyrophosphate-treated microsomes fortified with NADPH.
Oxidized chrysanthemic acid derivatives (VIII to XXII and XXVI) were comparatively stable.
The metabolites IV and VII were major products only in the presence of NADPH and the
supernatant fraction. Compounds II, III, V and VI were not isolated.
Some degradative products of the resmethrins are 5-benzyl-3-furoic acid, chrysanthemic
acid, the intermediary alcohol and aldehyde oxidation products, and conjugates of each of
these acids. The isobutenyl moiety is oxidized products, and conjugates of each of these
acids. The isobutenyl moiety is oxidized at either the cis-or trans-methyl group in
(+)-cis-resmethrin, but only at the trans-methyl
group in (+)-trans-resmethrin. An unanticipated
metabolic pathway involves epimerization at C-3 of the cyclopropane ring. Some metabolites
of (+)-trans-resmethrin are more toxic than the
parent compound.
When four resmethrin isomers ([1R,trans]-,
[1S,trans]-, [1R,cis]-, and [1S,cis]-) were incubated with mouse and rat microsomes in 50
mmol/litre tris-HCl buffer (pH 7.4) at 37 deg C for 1 h, microsomal esterases readily
cleaved the trans- but not the cis-isomers. The ester linkage also appeared to undergo
oxidative cleavage when esterase attack was minimal. Ester metabolites were detected in
significant amounts only with [1R,cis]-resmethrin
in which case oxidation had occurred at isobutenyl moiety, with or without oxidation at
the benzylfuryl methyl group. Most of the in vitro metabolites were identical with those
in the excreta of rats given resmethrin orally.
The preferred site of oxidation in the isobutenyl moiety varies with the resmethrin
isomer and microsomal source. Mouse microsomes predominantly oxidized the trans-methyl
group of both [1R,trans]- and [1S,trans]- resmethrin,
the selectivity, however, being the greatest with [1S,trans]-resmethrin.
Rat microsomes were relatively nonselective in attacking the isobutenyl methyl groups of
[1R,trans]-resmethrin.
PYRETHROID INSECTICIDE CIS- & TRANS(+)- & -(-)-RESMETHRIN
IS HYDROLYZED BY RAT-LIVER MICROSOMAL ENZYME. TRANS-ISOMERS ARE HYDROLYZED 10-20 TIMES
FASTER THAN CIS-ISOMERS. LATTER ARE ALSO METABOLIZED AT OTHER SITES IN THE MOLECULE
(REFLECTING GREATER AVAIL FOR MONO-OXYGENATION). ... WHEN THE SLOWLY HYDROLYZED
CIS-ISOMERS WERE INCUBATED WITH MICROSOMES, AN NADPH-DEPENDENT ESTER CLEAVAGE WAS NOTED. A
SIMILAR REACTION WAS FOUND WHEN RAPIDLY HYDROLYZED TRANS-ISOMERS WERE INCUBATED WITH
TEPP-TREATED /TETRAETHYL PYROPHOSPHATE/ (ESTERASE-INHIBITED) MICROSOMES. THE METABOLITE
DERIVED FROM ALCOHOL MOIETY ... WAS NOT FULLY CHARACTERIZED.
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/
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/
The metabolic pathways for the breakdown of the pyrethroids vary little between
mammalian species but vary somewhat with structure. ... Essentially, pyrethrum &
allethrin are broken down mainly by oxidation of the isobutenyl side chain of the acid
moiety & of the unsaturated side chain of the alcohol moiety with ester hydrolysis
playing an important part, whereas for the other pyrethroids ester hydrolysis
predominates. /Pyrethrum and pyrethroids/
The low toxicity of pyrethroids in mammals is due largely to their rapid
biotransformation by ester hydrolysis and/or hydroxylation. /Pyrethroids/
Absorption, Distribution & Excretion:
The cis- & trans- isomers of the synthetic pyrethroid resmethrin,
labeled with radiocarbon in either the alcohol or acid moiety, were individually admin
orally to White Leghorn laying hens at 10 mg/kg. With each isomer & label position,
>90% of the radiocarbon was eliminated in the excreta within 24 hr after the treatment.
Radiocarbon residues in the egg white & yolk fractions were low, with peak levels
observed 1 & 4-5 days after treatment in white & yolk, respectively. In birds
sacrificed 12 hr after treatment, radiocarbon residues in tissues were low; the highest
levels were found in the liver & kidney.
Resmethrin (insecticide) labeled with
radiocarbon in either the acid or alcohol moiety & admin orally to lactating Jersey
cows at 10 mg/kg was rapidly absorbed, metabolized, & excreted. The cis-isomer was
eliminated primarily in the feces, but the trans-isomer was eliminated primarily in the
urine. Tissue residues at 48 hr post-treatment were low (<1 ppm) except in liver &
kidney which were generally higher with the alcohol labeled compounds. ...
Six days after admin of (14)C-resmethrin to
rats at a dose of 1 mg/kg, 53-73% was accounted for in urine & feces. Low residue
levels were observed in tissues. In urine, there were almost equal parts of free &
conjugated metabolites.
When (14)C-[1RS,trans]-resmethrin labelled in
the alcohol moiety was admin orally to Sprague-Dawley rats at 500 mg/kg, the radiocarbon
was rapidly absorbed from the GI tract & it took 3 wk for the complete elimination of
the radioactivity in the urine (36% of the dose) & feces (64%). A negligible amount
(<0.1%) of the radiocarbon was expired as (14)CO2. The radiocarbon was not completely
excreted, even after 2 wk, in rats given an iv dose of 50 mg/kg; notably, appreciable
amounts of (14)C were found in feces.
/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/
Mechanism of Action:
PYRETHROIDS ARE DIVIDED INTO 2 CLASSES (TYPES I & II) BASED ON THEIR EFFECTS ON
CERCAL SENSORY NERVES & ON SYMPTOMATOLOGY THEY PRODUCED IN DOSED COCKROACHES. TYPE I
INCL RESMETHRIN.
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 ((3H)H12-HTX) 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 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. /Pyrethroids/
/In rat brain in vitro/ resmethrin (at 30 uM)
induced the release of transmitters was not affected by manipulation of the Na+ current
with either choline or tetrodotoxin agents ... . Resmethrin
(at 2.2 uM) inhibited the ATP-dependent uptake of Ca+ ... also it displaced Ca+ from crude
synaptosomal membranes.
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.
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 symptoms of pyrethrin poisoning follow the typical pattern ... : (1) excitation,
(2) convulsions, (3) paralysis, and (4) death. The effects of pyrethrins on the insect
nervous system closely resemble those of DDT, but are apparently much less persistent.
Regular, rhythmic, and spontaneous nerve discharges have been observed in insect and
crustacean nerve-muscle preparations poisoned with pyrethrins. The primary target of
pyrethrins seems to be the ganglia of the insect central nervous system although some
pyrethrin-poisoning effect can be observed in isolated legs. /Pyrethrins/
Electrophysiologically, pyrethrins cause repetitive discharges and conduction block.
/Pyrethrins/
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/
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/
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/
Resmethrin (30 umol/litre)-induced release of
transmitters was not affected by manipulation of the Na+ current with either choline or
tetrodotoxin agents, which readily reversed the effects of veratridine, deltamethrin, and
cypermethrin. Resmethrin (I50: 2.2 umol/litre)
inhibited the ATP-dependent uptake of Ca2+ but deltamethrin and cypermethrin were much
less effective. Resmethrin also displaced Ca2+
from crude synaptosomal membranes. The release-promoting effects of resmethrin
in rat brain in vitro are better explained by its effects on Ca2+ rather than by a
specific effect on the Na+ channel. In contrast, deltamethrin and cypermethrin promote
transmitter release by a Na+ dependent process.
Interactions:
/Pyrethroid/ detoxification ... important in flies, may be delayed by the addition of
synergists ... organophosphates or carbamates ... to guarantee a lethal effect. ...
/Pyrethroid/
Piperonyl butoxide potentiates /insecticidal activity/ of pyrethrins by inhibiting the
hydrolytic enzymes responsible for pyrethrins' metabolism in arthropods. When piperonyl
butoxide is combined with pyrethrins, the insecticidal activity of the latter drug is
increased 2-12 times /Pyrethrins/
At dietary level of 1000 ppm pyrethrins & 10000 ppm piperonyl butoxide ...
/enlargement, margination, & cytoplasmic inclusions in liver cells of rats/ were well
developed in only 8 days, but ... were not maximal. Changes were proportional to dosage
& similar to those produced by DDT. Effects of the 2 ... were additive. /Pyrethrins/
Pharmacology:
Therapeutic Uses:
Pyrethrins with piperonyl butoxide are used for topical treatment of pediculosis (lice
infestations). Combinations of pyrethrins with piperonyl butoxide are not effective for
treatment of scabies (mite infestations). Although there are no well-controlled
comparative studies, many clinicians consider 1% lindane to be pediculicide of choice.
However, some clinicians recommend use of pyrethrins with piperonyl butoxide, esp in
infants, young children, & pregnant or lactating women ... . If used correctly, 1-3
treatments ... are usually 100% effective ... Oil based (eg, petroleum distillate)
combinations ... produce the quickest results. ... For treatment of pediculosis, enough
gel, shampoo, or solution ... should be applied to cover affected hair & adjacent
areas ... After 10 min, hair is ... washed thoroughly ... treatment should be repeated
after 7-10 days to kill any newly hatched lice. /Pyrethrins/
Interactions:
/Pyrethroid/ detoxification ... important in flies, may be delayed by the addition of
synergists ... organophosphates or carbamates ... to guarantee a lethal effect. ...
/Pyrethroid/
Piperonyl butoxide potentiates /insecticidal activity/ of pyrethrins by inhibiting the
hydrolytic enzymes responsible for pyrethrins' metabolism in arthropods. When piperonyl
butoxide is combined with pyrethrins, the insecticidal activity of the latter drug is
increased 2-12 times /Pyrethrins/
At dietary level of 1000 ppm pyrethrins & 10000 ppm piperonyl butoxide ...
/enlargement, margination, & cytoplasmic inclusions in liver cells of rats/ were well
developed in only 8 days, but ... were not maximal. Changes were proportional to dosage
& similar to those produced by DDT. Effects of the 2 ... were additive. /Pyrethrins/
Environmental Fate & Exposure:
Environmental Fate/Exposure Summary:
Resmethrin's production and use as a contact
insecticide effective against a wide range of insects has resulted in its direct release
to the environment. If released to air, a vapor pressure of 1.1X10-8 mm Hg at 30 deg C
indicates resmethrin will exist solely in the
particulate phase in the ambient atmosphere. Resmethrin
undergoes direct photolysis in the environment. The photolysis half-life of resmethrin films on glass plates ranged from about 20
to 90 minutes when exposed to forenoon and midday sunlight conditions. Particulate phase resmethrin may be removed from the atmosphere by wet
and dry deposition. If released to soil, resmethrin
is expected to have no mobility based upon an estimated Koc of 21,400. Volatilization from
moist soil surfaces is not expected to be an important fate process based upon an
estimated Henry's Law constant of 1.3X10-7 atm-cu m/mole. Resmethrin
is not expected to volatilize from dry soil surfaces based upon its vapor pressure. Resmethrin is expected to undergo hydrolysis in moist
soil under alkaline conditions and may also undergo direct photolysis on soil surfaces.
Although biodegradation data for resmethrin are
not available, the pyrethroid class of insecticides is readily degraded by environmental
microorganisms and based upon its structure, resmethrin
is also expected to biodegrade readily. If released into water, resmethrin
is expected to adsorb to suspended solids and sediment based upon the estimated Koc.
Volatilization from water surfaces is not expected to be an important fate process based
upon this compound's estimated Henry's Law constant. Hydrolysis is an important
environmental fate process based upon estimated hydrolysis half-lives of 1.3 yrs, 47 days
and 4.7 days at pH 7, 8 and 9, respectively. Photolysis in surface waters is also expected
to be an important fate process. The predicted near-surface half-life for the
photosensitized oxidation of resmethrin in
natural water has been reported as 0.2 hr. An estimated BCF of 68 suggests the potential
for bioconcentration in aquatic organisms is moderate. Occupational exposure to resmethrin may occur through inhalation and dermal
contact with this compound at workplaces where resmethrin
is produced or used. Since resmethrin is a
widely used insecticide that can be employed for the control of a variety of insects,
mosquitos, and in pet sprays and shampoos, the general population may be exposed to
resmethrind through use of insecticides containing this compound. (SRC)
Probable Routes of Human Exposure:
NIOSH (NOES Survey 1981-1983) has statistically estimated that 27,596 workers (3,998 of
these are female) are potentially exposed to resmethrin
in the US(1). Occupational exposure to resmethrin
may occur through inhalation and dermal contact with this compound at workplaces where resmethrin is produced or used(SRC). Resmethrin
was detected in indoor air of 10 commercial pest control firms in North Carolina at concns
of 0.31-5.22 ug/cu m(2). Since resmethrin is a
widely used insecticide that can be employed for the control of a variety of insects,
mosquitos, and in pet sprays and shampoos, the general population may be exposed to
resmethrind through use of insecticides containing this compound(SRC). Resmethrin
was identified, but not quantified, in households after application from spray cans, pet
shampoos and hand-pumped broadcast sprayers(3).
Average Daily Intake:
Using the Total Exposure Assessment Methodology (TEAM), air samples in residential
households were collected over 24-hr periods in indoor, outdoor and personal air in two
areas (Jacksonville, FL and Springfield/Chicopee, MA)(1); based upon air sample
detections, the annual avg daily concn to resmethrin
was estimated to be 0.1 ng/cu m in Jacksonville, FL(1); resmethrin
was not detected in the MA area samplings(1).
Artificial Pollution Sources:
Resmethrin's production and use as a contact
insecticide effective against a wide range of insects(1) is expected to result in its
direct release to the environment(SRC).
Environmental Fate:
TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of
21,400(SRC), determined from a log Kow of 5.43(2) and a regression-derived equation(3),
indicates that resmethrin is expected to be
immobile in soil(SRC). Volatilization of resmethrin
from moist soil surfaces is not expected to be an important fate process(SRC) given an
estimated Henry's Law constant of 1.3X10-7 atm-cu m/mole(SRC), calculated from its vapor
pressure of 1.1X10-8 mm Hg(4) and water solubility of 0.0379 mg/l(2). Resmethrin
is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor
pressure(2). Although biodegradation data for resmethrin
are not available, the pyrethroid class of insecticides is readily degraded by
environmental microorganisms(5,6) and based upon its structure, resmethrin
is also expected to biodegrade readily(5,6). Hydrolysis in moist soil surfaces is expected
to be an important fate process for resmethrin
under alkaline conditions(SRC). The second-order aqueous hydrolysis rate constant for resmethrin has been estimated to be 0.1705 L/mole-sec
at 25 deg C(SRC) using a structure estimation method(7), which corresponds to aqueous
hydrolysis half-lives of 1.3 yrs, 47 days and 4.7 days at pH 7, 8 and 9,
respectively(SRC). Photolysis may also be an important fate process for this compound on
soil surfaces(SRC). The photolysis half-life of resmethrin
films on glass plates ranged from about 20 to 90 minutes when exposed to forenoon and
midday sunlight conditions(8).
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of
21,400(SRC), determined from a log Kow of 5.43(2) and a regression-derived equation(3),
indicates that resmethrin is expected to adsorb
to suspended solids and sediment(SRC). Volatilization from water surfaces is not
expected(3) based upon an estimated Henry's Law constant of 1.3X10-7 atm-cu m/mole(SRC),
calculated from its vapor pressure of 1.1X10-8 mm Hg(4) and water solubility of 0.0379
mg/l(2). According to a classification scheme(5), an estimated BCF of 68(SRC), from its
log Kow(2) and a regression-derived equation(6), suggests the potential for
bioconcentration in aquatic organisms is moderate(SRC). Hydrolysis is expected to be an
important environmental fate process for resmethrin,
particularly in alkaline waters(SRC). The second-order aqueous hydrolysis rate constant
for resmethrin has been estimated to be 0.1705
L/mole-sec at 25 deg C(SRC) using a structure estimation method(7), which corresponds to
aqueous hydrolysis half-lives of 1.3 yrs, 47 days and 4.7 days at pH 7, 8 and 9,
respectively(SRC). Photolysis in surface waters is also expected to be an important fate
process(SRC). The predicted near-surface half-life for the photosensitized oxidation of resmethrin in natural water has been reported as 0.2
hr(8). Although biodegradation data for resmethrin
are not available, the pyrethroid class of insecticides is readily degraded by
environmental microorganisms(9,10) and based upon its structure, resmethrin
is also expected to biodegrade readily(9,10).
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile
organic compounds in the atmosphere(1), resmethrin,
which has a vapor pressure of 1.1X10-8 mm Hg at 30 deg C(2) is expected to exist solely in
the particulate phase in the ambient atmosphere. Particulate phase resmethrin
may be removed from the atmosphere by wet and dry deposition(SRC). Resmethrin
undergoes rapid photolysis in the environment with half-lives on the order of several
minutes to a few hours(3-5).
Environmental Biodegradation:
Although environmental biodegradation data specific to resmethrin
are not available, the pyrethroid class of insecticides is readily degraded by
environmental microorganisms(1,2); based upon its structure, resmethrin
are also expected to biodegrade readily(1,2).
Environmental Abiotic Degradation:
Photodecomposition of (+)-cis-resmethrin
produced cis-chrysanthemic acid; benzaldehyde; phenylacetic acid;
5-benzyl-5-hydroxy-2-oxo-2,5-dihydro-3- furylmethyl cis-chrysanthemate and
4-benzyl-5-hydroxy-3-oxo-cyclopent-1,2- enylmethyl cis-chrysanthemate.
Irradiation of the (+)-trans-isomer produced 11 photoproducts. The major component was
trans-chrysanthemic acid. Other compounds observed included benzaldehyde (VIII);
2-benzyloxy-5-oxo-2,5-dihydro-3-furylmethyl trans-chrysanthemate (IV); compound III,
compound V, benzyl alcohol, benzoic acid, phenylacetic acid and two epoxyresmethrin
isomers.
The second-order aqueous hydrolysis rate constant for resmethrin
has been estimated to be 0.1705 L/mole-sec at 25 deg C(SRC) using a structure estimation
method(1), which corresponds to aqueous hydrolysis half-lives of 1.3 yrs, 47 days and 4.7
days at pH 7, 8 and 9, respectively(SRC). When films on glass were exposed to outdoor
sunlight, (+)-trans-resmethrin decomposed very
rapidly (within 24 hr)(2). The photodegradation half-life of resmethrin
(adsorbed to silica gel) irradiated with a sunlamp was observed to be about 200 min(3);
virtually no degradation occurred in dark control(3); a 15-min exposure of resmethrin (adsorbed to silica gel) to sunlight
resulted in a 29% photodecomposition(3); 90-min sunlamp exposures on a glass plate and on
filter paper resulted in respective disappearances of 32% and 64%(3); a 60-min sunlamp
exposure of resmethrin in water resulted in 25%
photodecomposition(3). Photodecomposition products of resmethrin
include chrysanthemic acid, phenylacetic acid, benzyl alcohol, benzaldehyde, benzoic acid,
and various chrysanthemates(3). The predicted near-surface half-life for the
photosensitized oxidation of resmethrin in
natural water has been reported as 0.2 hr(4). The photolysis half-life of resmethrin films on glass plates ranged from about 20
to 90 minutes when exposed to forenoon and midday sunlight conditions(5). The fastest
rates were observed during midday sunlight and in the presence of the sensitizer methylene
blue. Resmethrin was also shown to undergo
direct photolysis when resmethrin aerosols were
irradiated with sunlight(5).
Environmental Bioconcentration:
An estimated BCF of 68 was calculated for resmethrin(SRC),
using a log Kow of 5.43(1) and a regression-derived equation(2). According to a
classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic
organisms is moderate(SRC).
Soil Adsorption/Mobility:
The Koc of resmethrin is estimated as
21,400(SRC), using a measured log Kow of 5.43(1) and a regression-derived equation(2).
According to a classification scheme(3), this estimated Koc value suggests that resmethrin is expected to be immobile in soil(SRC).
Volatilization from Water/Soil:
The Henry's Law constant for resmethrin is
estimated as 1.3X10-7 atm-cu m/mole(SRC) based upon its vapor pressure, 1.1X10-8 mm Hg(1),
and water solubility, 0.0379 mg/l(2). This Henry's Law constant indicates that resmethrin is expected to be essentially nonvolatile
from water surfaces(3). Resmethrin is not
expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).
Atmospheric Concentrations:
INDOOR AIR: Resmethrin was detected in indoor
air of 10 commercial pest control firms in North Carolina at concns of 0.31-5.22 ug/cu
m(1). Resmethrin was identified, not quantified,
in indoor air of homes following its application from aerosol spray cans and compressed
air sprayers(2).
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. Resmethrin is found on List A, which contains most
food use pesticides and consists of the 194 chemical cases (or 350 individual active
ingredients) for which EPA issued registration standards prior to FIFRA, as amended in
1988. Case No: 0421; Pesticide type: insecticide; Registration Standard Date: 12/88; 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): Resmethrin; Data Call-in
(DCI) Date(s): 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 are established for residues of the insecticide resmethrin
[5-phenylmethyl)-3-furanyl] methyl
2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylate in or on food items resulting
from use of the insecticide in food handling and storage areas as a space concentration
for spot/or crack and crevice treatment and shall be limited to a maximum of 3.00% of the
active ingredient by weight, and as a space treatment shall be limited to a maximum of 0.5
fluid ounce of 3.0% active ingredient by weight per 1000 cubic feet or space provided that
the food is removed or covered prior to such use. To assure safe use of the additive, its
label and labeling shall conform to that registered with the U.S. EPA, and shall be used
in accordance with such label and labeling.
Acceptable Daily Intakes:
OPP RfD= 0.03 mg/kg; EPA RfD= 0.03 mg/kg
Allowable Tolerances:
Tolerances are established for residues of the insecticide resmethrin
[5-phenylmethyl)-3-furanyl] methyl
2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylate in or on food items at 3.0 ppm
resulting from use of the insecticide in food handling and storage areas as a space
concentration for spot/or crack and crevice treatment and shall be limited to a maximum of
3.00% of the active ingredient by weight, and as a space treatment shall be limited to a
maximum of 0.5 fluid ounce of 3.0% active ingredient by weight per 1000 cubic feet or
space provided that the food is removed or covered prior to such use. To assure safe use
of the additive, its label and labeling shall conform to that registered with the U.S.
EPA, and shall be used in accordance with such label and labeling.
Chemical/Physical Properties:
Molecular Formula:
C22-H26-O3
Molecular Weight:
338.4
Color/Form:
Waxy off-white to tan solid
Colorless crystals
Odor:
Chrysanthemate odor
Boiling Point:
Decomposes at >180 deg C
Melting Point:
56.5 deg C (pure (1-RS)-trans isomer)
Corrosivity:
Non-corrosive
Density/Specific Gravity:
0.958-0.968 @ 20 deg C
Octanol/Water Partition Coefficient:
log Kow= 5.43
Solubilities:
Very sol in xylene and aromatic petroleum hydrocarbons; solubility in kerosene 10%
INSOL IN WATER @ 25 DEG C; METHYLENE CHLORIDE @ 25 DEG C: GREATER THAN 50% WT/WT; IN
ACETONE @ 25 DEG C: GREATER THAN 50% WT/WT; IN ETHANOL & ISOPROPANOL 8 & 7%,
/RESPECTIVELY/
In water, 0.0379 mg/l @ 25 deg C
Spectral Properties:
Refractive index at 20 deg C= 1.5287
Vapor Pressure:
1.13X10-8 mm Hg @ 30 deg C
Other Chemical/Physical Properties:
Wax solid /Technical resmethrin/
Mp: 43-48 deg C (isomeric mixture with 20-30% cis and 80-70% trans)
... Contains 20-30% (1RS)-cis-and 80-70% (1RS)-trans-isomers.
Chemical Safety & Handling:
Skin, Eye and Respiratory Irritations:
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.
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 Reactivities & Incompatibilities:
Incompatibility: Strong oxidizers. /Pyrethrins/
... Incompatible with lime & ordinary soaps because acids & alkalies speed up
processes of hydrolysis. /Pyrethrins/
Hazardous Decomposition:
When heated to decomp it emits acrid and irritating fumes.
Decomposes rapidly on exposure to air and light (more slowly than pyrethrins).
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: Contaminated protective clothing should be segregated in such a manner so that
there is no direct personal contact by personnel who handle, dispose, or clean the
clothing. Quality assurance to ascertain the completeness of the cleaning procedures
should be implemented before the decontaminated protective clothing is returned for reuse
by the workers. Contaminated clothing should not be taken home at end of shift, but should
remain at employee's place of work for cleaning.
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 and to oxidation. Decomposes rapidly on exposure to air and light (more
slowly than pyrethrins). Unstable in alkaline media.
Pyrethrins ... /are/ stable for long periods in water-based aerosols where ...
emulsifiers give neutral water systems. /Pyrethrins/
Storage Conditions:
... /Store/ under dry conditions.
Store away from food and feedstuffs. ...
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/
Cleanup Methods:
Spillages of pesticides at any stage of their storage or handling should be treated
with great care. Liquid formulations may be reduced to solid phase by evaporation. Dry
sweeping of solids is always hazardous: these should be removed by vacuum cleaning /SRP:
with HEPA filter/, or by dissolving them in water, or other solvent in the factory
environment. /Pesticides/
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.
It could be ... buried in noncrop land away from water. In each of these cases it would
be better to mix the product with lime. Incineration would be an effective disposal
procedure where permitted. If an efficient incinerator is not available, the product
should be mixed with large amt of combustible material. Recommendable methods: Hydrolysis,
landfill, incineration, & open burning. Not recommendable method: Discharge to sewer.
Peer-review: Mix with sawdust and burn at a remote place. (Peer-review conclusions of an
IRPTC expert consultation (May 1985))
Incineration would be an effective disposal procedure where permitted. ... /Pyrethrin
products/
Occupational Exposure Standards:
Manufacturing/Use Information:
Major Uses:
For Resmethrin (USEPA/OPP Pesticide Code:
097801) 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./
... potent contact insecticide effective against a wide range of insects.
... HIGHLY ACTIVE INSECTICIDE RECOMMENDED FOR USE AGAINST HOUSEFLIES, GERMAN
COCKROACHES. ...
APPLIED ON INSECTS FOUND IN HOUSEHOLD, GREENHOUSE, INDOOR LANDSCAPING, MUSHROOM HOUSES,
INDUSTRIAL, STORED PRODUCT, MOSQUITO & INSECT CONTROL.
PET SPRAYS, PET SHAMPOO, AND APPLICATION ON HORSES AND HORSE STABLES.
CLEARED FOR USE IN AEROSOLS, AQUEOUS PRESSURIZED SPRAYS, EMULSIFIABLE CONCENTRATES,
TRANSPARENT EMULSIONS, & OIL BASE LIQ, INCL ULV CLEARED FOR FABRIC PROTECTION.
Resmethrin (2%) has replaced Pyrethrum-DDT
formulation in aircraft disinfection.
Control of wood lice
Resmethrin is currently used for mosquito
control (by aerial application) in the USA, and it can also be used for the control of
white fly in greenhouses.
Resmethrin is mainly used in aerosol
formulations, but also in oil formulations and emulsifiable concentrates, for the control
of household and public health insects. It is also used in combination with other
insecticides (e.g., tetramethrin, malathion).
MEDICATION
Methods of Manufacturing:
ESTERIFICATION OF 5-BENZYL-3-FURYLMETHYL ALCOHOL (BRITISH PATENTS 1168797-9) ...
CONTAINING 20-30% OF THE (+/-)-CIS ISOMER AND 80-90% OF THE (+/-)-TRANS.
ESTERIFICATION OF ETHEREAL 5-BENZYL-3-FURYLMETHYL ALCOHOL WITH
(+/-)-CIS,TRANS-CHRYSANTHEMIC ACID CHLORIDE IN BENZENE. AFTER ADDING PYRIDINE, AND
STANDING OVERNIGHT, WATER IS ADDED AND THE ORGANIC LAYER WASHED WITH SULFURIC ACID,
POTASSIUM BICARBONATE, SODIUM CHLORIDE, DRIED AND THEN DISTILLED.
General Manufacturing Information:
Cleared for USDA meat and poultry inspection programs.
NIA 17370 discontinued by FMC Corporation
Compatible with other neutral insecticides and fungicides.
/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 097801; Trade Names: Synthrin,
NIA-17370, SBP 1382, Benzofuroline, Chrysron,
Pynosect, FMC 17370, Pyretherm, Premgard, For-Syn, NRDC 104.
Resmethrin /formulations/ contain
70%(+/-)trans-isomer and 30%(+/-)cis-isomer.
FOR-SYN
NRDC 104
PENICK 1382
Penncapthrin
Premgard
Pyretherm
Synthrin- Trade Name product from Fairfield
American
Tetramethrin with resmethrin (Tetralate)
Cismethrin
Bioresmethrin
Aerosol generator, emulsifiable concentrate, wettable powder, ultra-low volume liquid.
Mixtures include: resmethrin + tetramethrin; resmethrin + malathion.
Mixed formulations: (resmethrin+)
bioallethrin; pyrethrins; pyrethrins + piperonyl butoxide.
Resmethrin is supplied in a water- or
oil-based syrup, often in combination with tetramethrin.
Pyrethroids are formulated as emulsifiable concentrates, wettable powders, granules,
and concentrates for ultra low volume application. /Pyrethroids/
Laboratory Methods:
Clinical Laboratory Methods:
Residues of resmethrin are extracted from
most food products with acetonitrile and from milk with acetonitrile-acetone (95+5). The
extracts are cleaned up by partitioning with petroleum ether, followed by Florisil column
chromatography and then alumina column chromatography. The initial extraction step is
omitted for sugar samples, which are dissolved in distilled water. Resmethrin
is determined by gas chromatography with a column of 3% OV-1 on Gas-Chrom Q and flame
ionization detection. An alternative column of 3% OV-210 can be used if interfering peaks
appear in the initial chromatogram. In a method tryout, EPA obtained resmethrin
recoveries that ranged from 87 to 123% for milk samples fortified at the 0.1 and 1.0 ppm
levels; recoveries ranged from 78 to 106% for bread samples fortified at the same levels.
Product application: fruits, meat, milk, vegetables. Detection limt: 0.1 ppm.
Analytic Laboratory Methods:
Product and residue analysis are by gas liquid chromatography with flame ionization
detection with internal std such as dicyclohexyl phthalate or di-octyl phthalate. Cis- and
trans-isomer. ... separated and est by high pressure liq chromatography or by gas liquid
chromatography. Residues may be determined by gas liquid chromatography.
RESMETHRIN IN FORMULATED PRODUCT WAS ANALYZED
BY USING HIGH PERFORMANCE LIQ CHROMATOGRAPHY WITH SILICA COLUMN & CARBON TETRACHLORIDE
MOBILE PHASE CONTAINING ACETONITRILE (VOL/VOL).
TRANS-RESMETHRIN WAS SEPARATED BY THIN LAYER
CHROMATOGRAPHY ON SILICA GEL 60 F254, USING HEXANE-BENZENE-ACETONE MIXT (9:1:1). CMPD
DETERMINED BY FLAME IONIZATION GAS CHROMATOGRAPHY.
Cis and trans isomers of resmethrin,
permerthrin, allethrin, and ... fenvalerate were separated in less than 30 min using
reversed-phase high performance liquid chromatography . The separation procedure was
applied to the detection of residues of synthetic pyrethroids in ambient air to the
preparation of pure isomers of two of the compounds.
Five types of isomers of pyrethroids, ie, fenopathrin, resmethrin,
bioresmethrin, permethrin, phenothrin, fluvalinate, allethrin, and bioallethrin were
separated by Pirkle type 1-A chiral phase high performance liquid chromatography .
EAD Method 1660. The Determination of Pyrethrins and Pyrethroids in Municipal and
Industrial Wastewater by High-Performance Liquid Chromatography. Detection limit = 2 ug/l.
EMSLC Method 616. The Determination of Certain Carbon-, Hydrogen-, and
Oxygen-Containing Pesticides in Municipal and Industrial Wastewater by Gas Chromatography
with Flame Ionization Detection. Detection limit = 36 ug/l.
Special References:
Special Reports:
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.
Papadopoulou-Mourkidou E; Residue Rev 89: 179-208 (1983). A review with many references
on analysis of allethrin & other pyrethroid insecticides.
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.
Miyamato J; Environ Health Perspect 14: 15-28 (1976). Degradation, metabolism, and
toxicity of synthetic pyrethroids.
Hutson DH; Progress in Drug Metabolism 3: 215-252 (1979). The metabolic fate of
synthetic pyrethroid insecticides in mammals.
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:
BENZOFUROLINE
**PEER REVIEWED**
5-BENZYLFURFURYL CHRYSANTHEMATE
**PEER REVIEWED**
BENZYLFUROLINE
**PEER REVIEWED**
(5-BENZYL-3-FURYL) METHYL-2,2-DIMETHYL-3-(2-METHYLPROPENYL)-CYCLOPROPANECARBOXYLATE
**PEER REVIEWED**
5-BENZYL-3-FURYLMETHYL(+-)-CIS,TRANS-CHRYSANTHEMATE
**PEER REVIEWED**
(5-BENZYL-3-FURYL)METHYL CHRYSANTHEMATE
**PEER REVIEWED**
5-Benzyl-3-furylmethyl (1RS, 3RS; 1RS,
3SR)-2,2-dimethyl-3-(2-methylprop=1-enyl)cyclopropanecarboxylate
**PEER REVIEWED**
5-Benzyl-3-furylmethyl (1RS)-cis-trans-2,2-dimethyl-3-(2-methylprop-1-enyl)
cyclopropanecarboxylate
**PEER REVIEWED**
Chryson
**PEER REVIEWED**
CHRYSRON
**PEER REVIEWED**
CYCLOPROPANECARBOXYLIC ACID, 2,2-DIMETHYL-3-(2-METHYLPROPENYL)-, (4-(2-BENZYL)FURYL)
METHYL ESTER
**PEER REVIEWED**
CYCLOPROPANECARBOXYLIC ACID, 2,2-DIMETHYL-3-(2-METHYLPROPENYL)-,
(5-BENZYL-3-FURYL)METHYL ESTER
**PEER REVIEWED**
CYCLOPROPANECARBOXYLIC ACID, 2,2-DIMETHYL-3-(2-METHYL-1-PROPENYL)-,
(5-(PHENYLMETHYL)-3-FURANYL)METHYL ESTER
**PEER REVIEWED**
DIMETHYL 3-(2-METHYL-1-PROPENYL)CYCLOPROPANECARBOXYLATE
**PEER REVIEWED**
2,2-Dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylic acid
**PEER REVIEWED**
ENT 27474
**PEER REVIEWED**
Pesticide Code 097801
**PEER REVIEWED**
FMC 17370
**PEER REVIEWED**
FOR-SYN
**PEER REVIEWED**
Isathrine
**PEER REVIEWED**
NIA 17370
**PEER REVIEWED**
Nrdc 104
**PEER REVIEWED**
NSC 195022
**PEER REVIEWED**
OMS-1206
**PEER REVIEWED**
[5-Phenylmethyl-3-furan]methyl-2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropane
carboxylate.
**PEER REVIEWED**
(5-(Phenylmethyl)-3-furanyl) methyl 2,2-dimethyl-3-(2-methyl-1-propenyl)
cyclopropanecarboxylate)
**PEER REVIEWED**
(5-(Phenylmethyl)-3-furanyl)methyl ester
**PEER REVIEWED**
PREMGARD
**PEER REVIEWED**
Pynosect
**PEER REVIEWED**
PYRETHERM
**PEER REVIEWED**
Resmethrine
**PEER REVIEWED**
RESMETRINA (PORTUGUESE)
**PEER REVIEWED**
SBP 1382
**PEER REVIEWED**
SB Pennick 1382
**PEER REVIEWED**
Synthrin
**PEER REVIEWED**
Formulations/Preparations:
USEPA/OPP Pesticide Code 097801; Trade Names: Synthrin,
NIA-17370, SBP 1382, Benzofuroline, Chrysron,
Pynosect, FMC 17370, Pyretherm, Premgard, For-Syn, NRDC 104.
Resmethrin /formulations/ contain
70%(+/-)trans-isomer and 30%(+/-)cis-isomer.
FOR-SYN
NRDC 104
PENICK 1382
Penncapthrin
Premgard
Pyretherm
Synthrin- Trade Name product from Fairfield
American
Tetramethrin with resmethrin (Tetralate)
Cismethrin
Bioresmethrin
Aerosol generator, emulsifiable concentrate, wettable powder, ultra-low volume liquid.
Mixtures include: resmethrin + tetramethrin; resmethrin + malathion.
Mixed formulations: (resmethrin+)
bioallethrin; pyrethrins; pyrethrins + piperonyl butoxide.
Resmethrin is supplied in a water- or
oil-based syrup, often in combination with tetramethrin.
Pyrethroids are formulated as emulsifiable concentrates, wettable powders, granules,
and concentrates for ultra low volume application. /Pyrethroids/
RTECS Number:
NIOSH/GZ1310000
Administrative Information:
Hazardous Substances Databank Number: 1516
Last Revision Date: 20011010
Last Review Date: Reviewed by SRP on 5/10/2001
Update History:
Complete Update on 10/10/2001, 54 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 03/09/2000, 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 11/18/1999, 1 field added/edited/deleted.
Complete Update on 09/21/1999, 1 field added/edited/deleted.
Complete Update on 08/26/1999, 1 field added/edited/deleted.
Complete Update on 06/02/1998, 1 field added/edited/deleted.
Complete Update on 03/16/1998, 6 fields added/edited/deleted.
Field Update on 10/23/1997, 1 field added/edited/deleted.
Field Update on 05/08/1997, 1 field added/edited/deleted.
Field Update on 05/01/1997, 2 fields added/edited/deleted.
Complete Update on 10/13/1996, 1 field added/edited/deleted.
Complete Update on 05/10/1996, 1 field added/edited/deleted.
Complete Update on 03/21/1996, 1 field added/edited/deleted.
Complete Update on 01/21/1996, 1 field added/edited/deleted.
Complete Update on 12/28/1994, 1 field added/edited/deleted.
Complete Update on 03/25/1994, 1 field added/edited/deleted.
Complete Update on 03/01/1994, 58 fields added/edited/deleted.
Field update on 12/20/1992, 1 field added/edited/deleted.
Complete Update on 08/05/1991, 1 field added/edited/deleted.
Field update on 11/09/1990, 1 field added/edited/deleted.
Complete Update on 10/02/1990, 1 field added/edited/deleted.
Field Update on 05/14/1990, 1 field added/edited/deleted.
Field Update on 05/12/1988, 1 fields added/edited/deleted.
Complete Update on 02/24/1988, 46 fields added/edited/deleted.
Complete Update on 03/12/1987
Record Length: 144681