PHENOTHRIN
Human Health Effects:
Human Toxicity Excerpts:
d-Phenothrin (talc powder formulation with Span 80 as a stabilizer) was applied to the
head hair and pudendal hair of eight male human volunteers (three times at intervals of 3
days) at a dose of 32 mg/man per administration (0.44 to 0.67 mg/kg body weight per day).
d-Phenothrin powder was washed off 1 hr after application. There were no significant
abnormalities due to d-phenothrin in terms of dermal irritation, clinical signs, or blood
biochemical and hematological parameters. The blood levels of d-phenothrin were below the
detection limit ... .
One hundred and one subjects with head louse infestation were entered into two separate
studies, in which a phenothrin aqueous/alcoholic lotion was compared to a carbaryl lotion
and a malathion lotion. Fifty subjects were treated with a single application of the
phenothrin lotion, 28 with the carbaryl lotion and 23 with the malathion lotion. In the
comparative study of the phenothrin and malathion lotions an inspection on the day
following treatment showed no live lice remained, but that six of the subjects treated
with malathion lotion still had evidence of viable eggs (p < 0.05). In one subject
viable eggs were still evident at two weeks post-treatment. There were no cases, however,
of live lice or viable eggs at four weeks post-treatment. Mild cutaneous side-effects were
reported in five subjects, the incidence of which was not significantly different by
treatment group. One subject in the phenothrin and carbaryl lotion comparative study had
evidence of live lice at one week post-treatment with phenothrin lotion. This subject
received no further treatment and was clear of both live lice and viable eggs at
subsequent visits. A separate case of live lice infestation was found at two weeks
post-treatment in a subject treated with phenothrin lotion and at four weeks
post-treatment in two subjects treated with carbaryl lotion. As these subjects were free
of live lice infestation at previous follow-up visits it was highly probable that these
were cases of re-infestation from another source.
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:
Occupational exposure to phenothrin may occur through inhalation and dermal contact
with this compound at workplaces where phenothrin is produced or used. The general
population may be exposed to phenothrin via inhalation and dermal contact with
insecticides containing phenothrin. (SRC)
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 (eg, 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/
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:
SYNTHETIC PYRETHROIDS (INCL PHENOTHRIN) INCREASED FREQUENCY OF SPONTANEOUS DISCHARGES
IN ABDOMINAL NERVE CORD EXCISED FROM CRAYFISH, PROCAMBARUS CLARKI. THE INCREASE IN
FREQUENCY IS RELATED TO THEIR EFFECTS TO DEPOLARIZE THE RESTING AXONIC MEMBRANE &,
POSSIBLY, TO SUPPRESS RELEASE OF INHIBITORY TRANSMITTERS FROM SYNAPTIC NERVE ENDING.
Rats fed 6000 ppm for 2 years showed only a small reduction in weight gain.
In a standard 3-generation (2 liters per generation) reproduction study groups of rats
(8 male and 16 female Charles River albino rats per group) were fed racemic phenothrin at
dose levels of 0, 200, 600, or 2000 mg/kg diet. Various reproductive indices (i.e. mating
index, fecundity index, male fertility index, female fertility index and incidence of
parturition) were measured. The adult rats showed no significant mortality or
complications during the study, and the reproductive parameters revealed no significant
dose-related adverse effects attributable to phenothrin. Gross and microscopic findings
indicated no adverse effect resulting from dietary phenothrin. It was concluded that
phenothrin had no effect on reproduction.
d-Phenothrin was fed to Charles River CD rats (30 of each sex per group) at dose levels
of 0, 300, 1000, or 3000 mg/kg diet throughout two successive generations and up to the
maturation of a third generaton. At 300 and 1000 mg/kg, there was no adverse effect upon
mortality, somatic growth, development, or reproductive performance. At 3000 mg/kg,
mortality, body weight, and reproductive performance showed no significant response to
treatment, and selected F2 animals reared to maturity were in respects comparable with
control rats. However, F0 and F1 females and selected F2B male and female weanlings showed
a slight but consistent increase in the relative liver weight. The NOEL in this study was
1000 mg/kg diet.
Pregnant New Zealand White rabbits (17 per group) were administered racemic phenothrin
orally at dose levels of 0, 3, 10, or 30 mg/kg body weight on days 6 to 18 of gestation.
They were sacrificed on day 29 and the the young obtained by caesarian section were
examined. At 30 mg/kg, the body weight of females decreased during gestation, and there
was a slight decrease in the number of live young and a slight reduction in fetal weight.
Racemic phenothrin had no apparent teratogenic effect, as shown by a lack of gross
internal or external somatic abnormalities and by normal fetal skeletal development
following prenatal exposure.
Sprague Dawley rats exposed to d-phenothrin by inhalation at concentrations of up to
3760 mg/cu m for 4 h showed no toxic signs as a result of exposure. Histopathologically,
there were no compound-related alterations in the sciatic nerve.
When d-phenothrin was given to Sprague Dawley rats orally for 5 consecutive days (5
g/kg body weight per day), one out of ten female rats died after four doses and signs of
poisoning (piloerections and urinary incontinence) were noted in several of the animals.
However, these signs disappeared rapidly at the end of the treatment and there were no
other signs of poisoning such as leg weakness or ataxia. All pathological examination of
the sciatic nerve revealed minute changes in axon and myelin, characterized by very slight
axonal swelling, axonal disintegration, and/or demyelination. Since there were similar
changes in the control animals, it was suggested that they were not due to the
d-phenothrin. It was considered that the oral administration of very high doses of
d-phenothrin does not lead to the neurotoxic effects observed with several other
pyrethroid esters.
d-Phenothrin /was examined/ for its ability to induce chromosomal aberrations in vivo
using bone marrow cells. ICR mice were treated intraperitoneally with single doses of
2500, 5000, or 10,000 mg/kg body weight and sacrificed 6, 24, or 48 hr after treatment. No
chromosomal aberrations as a result of d-phenothrin treatment were detected.
A mutagenicity test with Escherichia coli (WP2 uvr) and Salmonella typhimurium (TA
1535, TA 1537, TA 1538, TA 98, and TA 100) using d-phenothrin at dose levels of up to 5
mg/plate with and without metabolizing enzyme system (S9 mix) yielded negative results,
whereas a positive control gave a significant number of mutants.
The ability of d-phenothrin to induce sister-chromatid exchanges (SCEs) was tested in
cultured mouse embryonic cells in vitro. At doses of 1X10-5, 1X10-4, and 1X10-3 mol/l
(with and without S9 mix), d-phenothrin did not induce any increase in the frequency SCEs.
In a DNA-repair test with Bacillus subtilis (M45 rec- and H17 wild type strains) using
dose levels of up to 5 mg/disk per plate, d-phenothrin did not inhibit the growth of any
strain at any dose level, whereas the positive control, mitomycin C, showed a clear
effect. The negative control gave a result similar to that of d-phenothrin.
In a host-mediated assay using Salmonella typhimurium G46 (indicator bacteria),
d-phenothrin in corn oil was given orally (twice with a 24-hr interval) to groups of six
male ICR mice at dose levels of 2500 or 5000 mg/kg body weight. Soon after the last
administration, each mouse was injected intraperitoneally with the indicator cells. Three
hours later, the bacterial mutation frequency in d-phenothrin-treated mice was no greater
than that in the control group.
B6C3F1 Hybrid mice (90 of each sex per group) were fed d-phenothrin in the diet at dose
levels of 0, 300, 1000, or 3000 mg/kg. Fifty of each sex per group were allocated to a
standard oncogenicity study lasting 104 weeks. The remaining mice were assigned to a
chronic toxicity study, where 10 of each sex per group were sacrificed for interim study
after 26 or 53 weeks and the remaining animals were examined after 78 weeks of treatment.
There were no compound-related effects on clinical signs, mortality, ophthalmology, blood
biochemistry, hematology, or urinalysis. However, body weight gains for males fed
d-phenothin at 3000 mg/kg were reduced and relative liver weights were increased in both
sexes fed 3000 mg/kg and in males receiving 1000 mg/kg. Microscopic examination revealed
that the incidence of periacinar hepatocyte hypertrophy with cytoplasmic eosinophilia was
higher in males fed 3000 mg/kg. The incidence of liver tumors appeared higher in
phenothrin-treated female mice than in control females, but the difference was not
statistically significant. It was concluded, therefore, that administration of
d-phenothrin to mice for 2 years at dietary levels of up to 3000 mg/kg diet did not
significantly disturb the tumor burden or tumor profile of B6C3F1 hybrid mice. The NOEL in
this study was 300 mg/kg diet for males (40 mg/kg body weight per day) and 1000 mg/kg diet
for females (164 mg/kg body weight per day).
When beagle dogs (six of each sex per group) were fed d-phenothrin at dose levels of 0,
100, 300, or 1000 mg/kg diet for 26 weeks, there were no compound-related abnormal
findings in mortality, clinical signs, body weight, food consumption, ophthalmology, gross
or microscopic pathology, hematology, or urinalysis studies. However, the alkaline
phosphatase activity in males fed 300 mg/kg and males and females fed 1000 mg/kg was
noted. The NOEL in this study was 300 mg/kg.
In a study of unscheduled DNA synthesis, Hela S3 cells were treated with d-phenothrin
at dose levels of 0, 0.25, 0.5, 1.0, 2.0 or 4.0 mg/ml in the presence of (3)H-thymidine
(with and without S9 mix) for 3 hr, and the incorporation of 3H-thymidine into DNA was
measured. There was no significant increase in the radioactivity of DNA from cells treated
with d-phenothrin.
In an in vitro chromosomal aberration test, Chinese hamster ovary cells (CHO-K1) were
treated with d-phenothrin (dose levels: 2 x 10-5 to 2 x 10-4 mol/litre for 24 and 48 hr in
the absence of S9 mix; 5 x 10-5 to 5 x 10-4 mol/litre for 6 hr in the presence of S9 mix).
No significant increase in the number of cells with chromosomal aberrations was observed.
Beagle dogs (four of each sex per group) were fed d-phenothrin at dose levels of 0,
100, 300, 1000, or 3000 mg/kg diet for 52 weeks. There were no significant effects on
clinical signs, body weight, food consumption, ophthalmology, or urinalysis. However,
decreases in erythrocyte count, hemoglobin concentration, hematocrit, and total blood
protein were noted in both male and female dogs fed 3000 mg/kg, whereas mean absolute and
relative liver weights increased. Compound-related histopathological alterations were
noted in the adrenal glands and liver. Focal degeneration of the adrenal cortex with
cytoplasmic deposition of crystalline material was seen in one male dog fed 1000 mg/kg and
four dogs fed 3000 mg/kg. The chemical nature or biological significance of this
crystalline material was not recorded. Hepatocytes appeared to enlarge slightly in one
male dog fed 1000 mg/kg and seven dogs fed 3000 mg/kg. The NOEL in this study was 300
mg/kg diet for males and 1000 mg/kg for females (8.24 and 26.77 mg/kg body weight per day
for males and females, respectively).
When Sprague Dawley rats (50 of each sex per group) were fed a diet containing racemic
phenothrin (0, 200, 600, 2000, and 6000 mg/kg diet) for 2 years, body weight and food
consumption were slightly depressed at 6000 mg/kg in both males and females. There were no
abnormal clinical or behavioral problems associated with phenothrin administration. The
survival rate of all groups of treated rats was similar to that of controls. Males fed
6000 mg/kg showed a significant increase in serum glutamine-pyruvate aminotransferase
activity. Ophthalmological examinations revealed some abnormalities, all of which appeared
to be age related. Histopathological examination revealed no significant differences
between the treated groups and the control group with respect to severity of lesions. No
histopathological changes suggestive of oncogenicity resulting from phenothrin treatment
were found.
When Swiss White mice (50 of each sex per group) were fed racemic phenothrin for 18
months at dose levels of 0, 300, 1000, or 3000 mg/kg diet, there were no significant
effects on mortality, clincial signs, hematologic values, clinical chemistry parameters,
or gross pathological findings. Slight body weight depression occurred in males fed 3000
mg/kg, and increased liver weight was found at the highest dose level in both males and
females. There was a statistically significant difference (compared with the controls) in
lung amyloidosis in the 1000 and 3000 mg/kg dose groups, but no significant increase in
tumors attributed to phenothrin ingestion.
[1R,cis]-Phenothrin (d-phenothrin) was administered to Sprague Dawley rats (20 of each
sex per group) at dose levels of 0, 1, 3, or 10 g/kg diet for 6 months. Ten rats of each
sex per group were sacrificed after 3 months. d-Phenothrin had no significant effect on
mortality, clinical signs, ophthalmology, urinalysis, or gross and histopathological
findings. The serum albumin level was elevated after 3 months in males fed 10 g/kg and in
females fed 3 or 10 g/kg, and after 6 months in males fed 3 or 10 g/kg. The
albumin-blobulin ratio was raised after 3 months in males fed 3 or 10 g/kg and in females
fed 10 g/kg, and in both males and females fed 10 g/kg after 6 months. Absolute and
relative liver weights in both males and females fed 3 or 10 g/kg were increased. Based on
these data, it was concluded that the NOEL for d-phenothrin in this study was 1 g/kg diet
for both sexes (55.4 mg/kg body weight per day for males and 63.3 mg/kg body weight per
day for females).
In a standard oncogenicity study, Fisher-344 rats (50 of each sex per group) were fed
d-phenothrin at dose levels of 0, 300, 1000 or 3000 mg/kg diet for at least 105 weeks in
males and at least 118 weeks in females. Additional rats (30 of each sex per group) were
assigned to a chronic toxicity study with a 52-week interim sacrifice. There were no
significant effects on clinical signs mortality, food and water consumption,
ophthalmology, blood biochemistry, hematology, or urinalysis. However, the body weight
gain in females fed d-phenothrin at 3000 mg/kg was reduced, and the relative liver weight
was increased in females fed 3000 mg/kg for 52 weeks and, at the end of the oncogenicity
study, in males fed 3000 mg/kg. Microscopic examination revealed that the incidence of
cystic dilatation of the sinuses of the mesenteric lymph nodes and of periacinar
hepatocytic hypertrophy was higher in males fed 3000 mg/kg for at least 105 weeks.
d-Phenothrin did not show any oncogenic activity to rats at up to 3000 mg/kg. Although at
this time and dose increase in the incidence of adenomas and carcinomas of the preputial
gland was seen in males, the 1988 Joint FAO/WHO Meeting on Pesticide Residues considered
it unlikely that this finding was of toxicological significance. The NOEL was 1000 mg/kg
diet for both sexes (47 mg/kg body weight per day for males and 56 mg/kg body weight per
day for females).
Pregnant New Zealand White rabbits (15 per group) were orally administered d-phenothrin
by intubation (0, 10, 100 or 1000 mg/kg body weight per day) on days 6 to 18 of gestation,
and were sacrificed on day 29 or 30. Following caesarian section, 50% of the pups were
maintained for 24 h to evaluate survival. No abnormalities were observed among the does
(body weight, food consumption, clinical observations, and necropsy) or fetuses
(implantation sites, corpora lutea, resorption sites, weight, condition, and viability).
Data on fetal survival and from internal and external examinations for abnormalities
showed no significant effects from administrating d-phenothrin during gestation.
d-Phenothrin was orally administered to pregnant ICR mice (17 or 18 per group) at dose
levels of 0, 30, 300, or 3000 mg/kg per body weight on days 7 to 12 of gestation (not
covering the whole period of organogenesis). The dams were sacrificed on day 18 of
gestation and the pups were obtained by caesarian section. Other mice (7 per group) were
given d-phenothrin at dose levels of 0, 300, or 3000 mg/kg to evaluate postnatal effects.
These mice were allowed to deliver naturally and the pups were kept for 29 days. At these
levels, d-phenothrin showed no adverse effects, as indicated by maternal growth, fetal
mortality and external and internal examination of fetuses for teratorgenic or embryotoxic
effects.
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/
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/
No d-phenothrin-attributable pharmacological effects were detected in various tests
(e.g., spontaneous movement of isolated guinea pig ileum, contraction of the rat phrenic
nerve diaphragm preparation, cadiopulmonary physiology of anaesthetized cats, coordination
and spontaneous movement of mice, and rectal temperature of rats) at doses of 100-300
ug/ml in vitro, 3 mg/kg intravenous, or 100-300 mg/kg intraperitoneal. A tentative arousal
response was recorded in the electroencephalogram of cats given d-phenothrin (4 mg/kg)
intraperitoneally, as is commonly observed in animals given synthetic pyrethroids.
The type I pyrethroids /including phenothrin/ 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, 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.
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 symptoms of pyrethrin poisoning follow the typical pattern of nerve poisoning: (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/
Non-Human Toxicity Values:
LD50 Rat oral greater than 500 mg/kg
LD50 Mouse oral greater than 500 mg/kg
LD50 Rat oral greater than 10000 mg/kg /(1R)-cis,trans-isomeric mixture/
LD50 Mouse oral greater than 10000 mg/kg /(1R)-cis,trans-isomeric mixture/
LD50 Mouse (male) iv 470 mg/kg /Racemic/
LD50 Mouse (female) iv 600 mg/kg /Racemic/
LD50 Mouse (male) iv 265 mg/kg
LD50 Mouse (female) iv 315 mg/kg
LC50 Rat (Sprague Dawley) >1210 mg/cu m/4 hr /Racemic/
LC50 Mouse (ICR) >1210 mg/cu m/4 hr /Racemic/
LC50 Rat (Sprague Dawley) >3760 mg/cu m/4 hr
LC50 Mouse (ICR) 1180 mg/cu m/4 hr
LD50 Rat percutaneous >2000 mg/kg
LC50 Rat inhalation >3760 mg/cu m/4 hr
Ecotoxicity Values:
LC50 Goldfish 0.25-0.5 mg/L/48 hr
LC50 Rainbow trout 0.0167 mg/L/96 hr /(1R)-cis,trans-isomeric mixture/
LC50 Bluegill (Lepomis macrochirus) 18 ug/l/96 hr /Conditions of bioassay not
specified/
LC50 Daphnia pulex @ 25 deg C, Static system 50,000 ug/l/3 hr /Racemic/
LC50 Daphnia pulex @ 25 deg C, Static system 25,000-50,000 ug/l/3 hr /(+)-trans/
LC50 Daphnia pulex @ 25 deg C, Static system 50,000 ug/l/3 hr /(+)-cis/
LC50 Daphnia pulex @ 25 deg C, Static system 50,000 ug/l/3 hr /(-)-trans/
LC50 Daphnia pulex @ 25 deg C, Static system 50,000 ug/l/3 hr /(-)-cis/
LC50 Killifish (Oryzias litipes) adult @ 25 deg C, 200 ug/l/48 hr /Racemic/
LC50 Killifish (Oryzias litipes) adult @ 25 deg C, 120 ug/l/48 hr /(+)-trans/
LC50 Killifish (Oryzias litipes) adult @ 25 deg C, 170 ug/l/48 hr /(+)-Cis/
LC50 Killifish (oryzias litipes) adult @ 25 deg C, 10,000 ug/l/48 hr /(-)-trans/
LC50 Killifish (Oryzias litipes) adult @ 25 deg C, 10,000 ug/l/48 hr /(-)-cis/
Metabolism/Pharmacokinetics:
Metabolism/Metabolites:
(14)C-PHENOTHRIN ... WAS ORALLY ADMIN AT ... 200 MG/KG TO MALE SPRAGUE-DAWLEY RATS. ...
URINE CONTAINED LOW LEVELS OF 3-PHENOXYBENZOIC ACID & ITS GLYCINE CONJUGATE & SOME
ETHER & WATER SOL MATERIAL. IN ADDN ...3-(4'-HYDROXYPHENOXY)BENZOIC ACID WAS PRESENT
& ACCOUNTED FOR 42.3% OF RADIOACTIVITY ... THIS COMPD WAS ... MAJOR METAB IN FECES BUT
ACCOUNTED FOR ONLY 11.9% OF ... RADIOACTIVITY. IN ADDN TO UNCHANGED PHENOTHRIN &
UNIDENTIFIED WATER & ETHER SOLUBLES, FECES CONTAINED 3-PHENOXYBENZOIC ACID & THE
GLYCINE CONJUGATE. 3-PHENOXYBENZYL ALCOHOL WAS NOT OBSERVED IN URINE OR FECES.
DERMAL & ORAL ADMIN OF (+)TRANS- & (+)CIS-PHENOTHRIN TO MALE RATS FROM DUST OR
EMULSIFIABLE CONCENTRATE PRODUCED NEARLY THE SAME METABOLITES. MAJOR METABOLITES FROM
(+)TRANS-ISOMER WERE 3-PHENOXYBENZOIC ACID & ITS GLYCINE CONJUGATE &
(3,4'-HYDROXYPHENOXY)BENZOIC ACID & ITS SULFATE. THE CIS-ISOMER GAVE LARGER AMOUNTS OF
ESTER METABOLITES.
When [1R,trans]-phenothrin was given to rats at 4, 10, or 200 mg/kg body weight (oral
single dose) or 4 mg/kg body weight (repetitive oral dose for 14 days), the sulfate
conjugate of 4'-OH-phenoxy benzoic acid was predominant, accounting for 28, 43, 28, and
55%, respectively, of the dose. In addition, phenoxy benzoic acid (4, 10, 5, and 6%), its
glycine conjugate (1,3,2, and 2%) and glucuronide (2,3,1, and 3%), and free
4'-OH-phenoxybenzoic acid (2,11,3, and 3%) were found. The sulfate conjugate of
3-(2'-hydroxyphenoxy)benzoic acid (2'-OH-PBacid) was also found as a minor metabolite.
When Sprague Dawley rats were administered a single oral dose of [1R,trans]-phenothrin
at 4 or 200 mg/kg body weight level or given an oral dose of 4 mg/kg body weight per day
for 14 days, unmetabolized compound was found in the feces (44-45, 44-60, and 14-16% of
the dose, respectively). An ester-form metabolite, the 4'-hydroxy phenoxy benzoic acid
derivative of trans-phenothrin, was also detected (0.4-0.6%).
When Sprague Dawley rats were given a single oral dose of [1R,cis]-phenothrin at 4 or
200 mg/kg body weight level or an oral dose of [1R,cis]-phenothrin at 4 mg/kg body weight
per day for 14 days, ester-form metabolites (1-9% of the dosed radioactivity) were found,
in additon to unmetabolized compound (17-50% of the dose). The urine contained
4'-OH-phenoxybenzoic acid as a sulfate conjugate (7-18%) and in the free form (0.3-1%),
and phenoxy benzoic acid as glycine or glucuronide conjugates and in the free form
(0.3-1%).
[IR,trans]-Phenothrin (1 mmol/l) was incubated with the 8000 g supernatant from a liver
homogenate of rats, mice, guinea-pigs, rabbits, or dogs at 37 deg C for 60 min in the
absence of NADPH. the supernatant from the guinea-pig was the most active in degrading
[1R,trans]-phenothrin, followed by that of dog, rabbit, rat, and mouse. The major
metabolite in all the mammalian species tested was 3-phenoxybenzyl alcohol (PBalc).
Smaller amounts of PBacid and trace amounts of 4'-OH-PBacid were also found. However, in
the presence of NADPH, the amounts of PBacid and unidentified ether-soluble metabolites
increased in all species except dog. In contrast to [1R-trans]-phenothrin,
[1R,cis]-phenothrin was hardly metabolized at all by the rat liver preparation in the
absence of NADPH. NADPH enhanced the degradation rate of the cis isomer, leading to the
formation of unidentified metabolites, while estercleaved metabolites such as PBacid,
PBalc and 4'-OH-PBacid were found in very small amounts. When [1R,trans]-, [1R,cis]-,
[1S,trans]-, and [1S,cis]-phenothrin were incubated with rat liver microsomes at 37.5 deg
C for 30-60 min to estimate Km and Vmax using a Lineweaver-Burk plot, the values for Km
(0.11-0.17 mmol/litre) were similar for the four isomers, whereas the values for Vmax were
different both the trans isomers values for Vmax 20-30 times larger than did the cis
isomers.
When male Sprague Dawley rats were given cis-phenothrin (200 mg/kg body weight), three
ester-form metabolites, which accounted for 14% of the dosed radioactivity, were found in
the feces. These were 4'hydroxy-cis-phenothrin (4'-OH-c-phe), an ester-form derivative
with the trans methyl of the isobutenyl group being oxidized to carboxyl gorup, and a
compound with the geminaldimethyl groups oxidized (2-OH-) in addition to both of the above
modifications (4'-OH,wt-acid, 2-OH(t)-c-phe).
The relative resistance of mammals to the pyrethroids is almost wholly attributable to
their ability to hydrolyze the pyrethroids rapidly to their inactive acid and alcohol
components, since direct injection into the mammalian CNS leads to a susceptibility
similar to that seen in insects. Some additional 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 intravenous route, moderate by slower oral absorption, and 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/
The metabolic pathways for the breakdown of the pyrethroids vary little between
mammalian species but vary somewhat with structure. ... Essentially, pyrethrum and
allethrin are broken down mainly by oxidation of the isobutenyl side chain of the acid
moiety and of the unsaturated side chain of the alcohol moiety with ester hydrolysis
playing and 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:
(14)C-PHENOTHRIN LABELED AT THE HYDROXYMETHYL GROUP OF THE ALCOHOL MOIETY, WAS ORALLY
ADMIN AT ... 200 MG/KG TO MALE SPRAGUE-DAWLEY RATS. ABSORPTION & ELIMINATION WAS
RAPID. ABOUT 60% OF RADIOACTIVITY WAS ELIMINATED IN URINE & 40% IN FECES IN 3 DAYS. IN
ADDN TO PHENOTHRIN, 3-PHENOXYBENZYL ALCOHOL & 3-PHENOXYBENZOIC ACID WERE FOUND IN
BRAIN, LIVER, KIDNEY & BLOOD. UNIDENTIFIED WATER & ETHER SOLUBLES WERE ALSO
PRESENT.
DERMAL ADSORPTION OF (+)TRANS- & (+)CIS-PHENOTHRIN INTO BODY OF MALE RATS FROM DUST
OR EMULSIFIABLE CONCENTRATE (EC) WAS ESTIMATED TO BE 3-7% & 8-17%. RATE OF ABSORPTION
WAS 4-5 TIMES FASTER WITH EC THAN WITH DUST. AMOUNT ABSORBED THROUGH SKIN WAS ALMOST
COMPLETELY EXCRETED INTO URINE & FECES WITHIN 6 DAYS. WHEN ADMIN ONCE ORALLY, AT RATE
OF 2 MG/KG (EITHER ISOMER), ABOUT 96% OF DOSE WAS RECOVERED IN EXCRETA DURING FOLLOWING 6
DAYS. A LARGER AMT OF (+)CIS-ISOMER WAS EXCRETED IN FECES THAN (+)TRANS-ISOMER & A
LARGER AMT OF (+)TRANS-ISOMER WAS EXCRETED IN URINE THAN (+)CIS-ISOMER.
The tissue residues in rats 7 days after a single oral dose of (14)C-(1R,cis)- or
(14)C-(1R,trans)-phenothrin at 10 mg/kg body weight were generally very low although the
fat showed somewhat higher residue levels (1-2.5 mg/kg). Similarly, high 14C residue
levels (up to 23 mg/kg) were found in the fat, 7 days after a single oral dose of the
[1R,cis] isomer at 200 mg/kg body weight.
Information concerning the comparative metabolism of racemic (1RS) phenothrin and its
d-isomer (1R) was obtained through a study of CD rats and ddY mice given a single oral
dose of either [1R,trans]-, [1S,trans]-, [1RS,trans]-, [1R,cis]-, [1S,cis]-, or
[1RS,cis]-phenothrin. The radiocarbon derived from each isomer was almost completely
eliminated from the rats and mice within six days after dosing. The trans isomers were
mainly eliminated in the urine (rat, 85-88%; mice, 65-75%) and the cis isomers mainly in
the feces (rat, 57-71%; mice, 54-71%). The amounts of (14)C in the urine and feces of rats
and mice treated with the [1R,trans] and [1R,cis] isomers did not differ significantly
from those corresponding to the [1RS,trans] and [1RS,cis] isomers, respectively. The (14)C
tissue residues were very low, except in the fat. There were no striking differences in
(14)C levels among the three trans isomers and the three cis isomers. The (14)C levels of
the cis isomers in fat (maximum 3.5 mg/kg) were three to seven times higher than those of
the trans isomers (less than 1 mg/kg). The major urinary and fecal metabolities were
remarkably similar in both rats and mice. In both rats and mice, there were virtually no
differences in the metabolic fate of the [1R,trans] and [1RS,trans] isomers or of the
[1R,cis] and [1RS,cis] isomers.
Following the dermal treatment of male Sprague Dawley rats with dust or emulsifiable
concentrates (EC) of either (14)C-[1R,trans]- or (14)C-[1R,cis]- phenothrin at 10 mg/kg
body weight, the (14)C absorption into the body was estimated to be 3-7% of the initial
dose with dust and 8-17% with the EC. After both dust and ECtreatments, the radiocarbon
excreta (as a percentage of the initial dose) recovered in the urine was 2.6-8.7% for the
trans isomer, and 1.5-4.8% for the cis isomer, and in the feces was 0.6-2.2% for the trans
isomer, and 3.0-12.3% for the cis isomer. Since the same metabolites are formed following
either oral exposure or dermal treatment, it appears that both phenothrin isomers undergo
the same metabolism once in the systemic circulation, regardless of the route of
administration.
When (14)C-[1R,cis]-phenothrin in corn oil was administered once orally to Sprague
Dawley male and female rats at 4 or 200 mg/kg body weight, the radiocarbon was excreted
into the urine (11-18%) and feces (81-87%) within 7 days. Similarly, when Sprague Dawley
rats were treated repeatedly with (14)C-[1R, trans] or (14)C-[1R,cis] isomers at 4 mg/kg
body weight per day for 14 days, the radiocarbon was rapidly and almost completely
excreted: 75-70% in urine and 24-29% in feces for the trans isomer, and 24% in the urine
and 72-73% in feces for the cis isomer.
/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/
Biological Half-Life:
DERMAL ADSORPTION OF (+)TRANS- & (+)CIS-PHENOTHRIN INTO BODY OF MALE RATS FROM DUST
OR EMULSIFIABLE CONCENTRATE (EC) WAS ESTIMATED TO BE 3-7% & 8-17%. RATE OF ABSORPTION
WAS 4-5 TIMES FASTER WITH EC THAN WITH DUST & T/2 IN BLOOD WAS 2-3 TIMES LONGER.
Mechanism of Action:
ALL PYRETHROIDS (WHICH INCL PHENOTHRIN) TESTED ON DESERT LOCUST (SCHISTOCERCA GREGARIA)
BLOCKED NEURALLY EVOKED MUSCLE CONTRACTIONS WITHIN 20 MIN. AMONG PYRETHROIDS TESTED 4
DIFFERENT EFFECTS WERE OBSERVED. KNOCKDOWN ACTIVITY OF ALL PYRETHROIDS WAS ASSOC WITH 1
PARTICULAR EFFECT, THE BLOCK OF NEURALLY EVOKED CONTRACTIONS.
Some synthetic pyrethroids given intravenously to rats cause either tremor (T-syndrome)
or choreoathetosis with salivation (CS-syndrome). However, d-phenothrin (>600 mg/kg
body weight) injected intravenously into the lateral tail vein caused neither T-syndrome
nor CS syndrome, due to its very low acute toxicity. From a study involving intracerebral
dosing with [1R,cis]- or [1R, trans]-phenothrin in mice, both compounds were classified as
Type I pyrethroids based on the occurrence of tremors and on neurophysiological studies in
cockroach cercal sensory nerves.
The effects of 4 different pyrethroid insecticides on sodium channel gating in
internally perfused, cultured mouse neuroblastoma cells (N1E-115) were studied using the
suction pipette, voltage clamp technique. Pyrethroids increased the amplitude of the
sodium current, sometimes by more than 200%. Activation of the sodium current occurred at
more hyperpolarized potentials than under control conditions. The declining phase of the
sodium current during depolarization was markedly slowed down and after repolarization of
the membrane a large, slowly decaying sodium tail current developed. Pyrethroids did not
affect the sodium current reversal potential, steady-state sodium inactivation or recovery
from sodium channel inactivation. The amplitude of the pyrethroid-induced slow tail
current was always proportional to the sodium current at the end of the preceding
depolarizing pulse. The rate of decay of the slow tail current strongly depended on
pyrethroid structure and increased in the order deltamethrin, cyphenothrin, fenfluthrin
and phenothrin. The rate of decay further depended on membrane potential and temperature.
Below -85 m V the instantaneous current-voltage relationship of the slow tail current
showed a negative slope conductance. The tail current decayed more slowly at low
temperatures. Arrhenius plots indicated that the relaxation of open sodium channels to a
closed state involved a higher energy barrier for pyrethroid-affected than for normal
channels. The energy barrier was higher after deltamethrin than after the non-cyano
pyrethroid fenfluthrin. It is concluded that in mammalian neuronal membrane pyrethroids
selectively reduce the rate of closing of sodium channels both during depolarization and
after repolarization of the nerve membrane.
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 (eg, 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 central nervous system 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, and most neurotransmitter
release is secondary to increased sodium entry. /Pyrethroids/
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 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 (3H)-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/
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/
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:
Phenothrin's production and use as an insecticide is expected to result in its direct
release to the environment. If released to air, a vapor pressure of 1.43X10-7 mm Hg at 21
deg C indicates phenothrin will exist in both the vapor and particulate phases in the
ambient atmosphere. Vapor-phase phenothrin 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 4 hours and 38 minutes, respectively.
Particulate-phase phenothrin will be removed from the atmosphere by wet and dry
deposition. If released to soil, phenothrin is expected to have no mobility based upon an
estimated Koc of 56,000. Volatilization from moist soil surfaces is expected to be an
important fate process based upon an estimated Henry's Law constant of 6.80X10-6 atm-cu
m/mole. However, adsorption to soil is expected to attenuate volatilization. Pyrethrins,
such as phenothrin, are expected to undergo rapid photodecomposition and biomineralization
in soils and aqueous systems. For example, residues of trans-phenothrin fell to <10 ppb
(initial concn unspecified) within 45 days in an aerobic soil. If released into water,
phenothrin is expected to adsorb to suspended solids and sediment based upon the estimated
Koc. 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 7 and 81 days, respectively. However, volatilization
from water surfaces is expected to be attenuated by adsorption to suspended solids and
sediment in the water column. An estimated BCF of 266 suggests the potential for
bioconcentration in aquatic organisms is high. However, bioconcentration studies on
compounds which are structurally similar suggest that bioconcentratoin may be lower than
that indicated, due to the ability of aquatic organisms to metabolize this class of
compounds readily. Estimated hydrolysis half-lives for phenothrin are 5.5 years and 200
days at pH values of 7 and 8, respectively. Occupational exposure to phenothrin may occur
through inhalation and dermal contact with this compound at workplaces where phenothrin is
produced or used. The general population may be exposed to phenothrin via dermal contact
with insecticides containing phenothrin. (SRC)
Probable Routes of Human Exposure:
Occupational exposure to phenothrin may occur through inhalation and dermal contact
with this compound at workplaces where phenothrin is produced or used. The general
population may be exposed to phenothrin via inhalation and dermal contact with
insecticides containing phenothrin. (SRC)
Artificial Pollution Sources:
Phenothrin's production and use as an insecticide(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
56,000(SRC), determined from a water solubility of 9.70X10-3 mg/l(2) and a
regression-derived equation(3), indicates that phenothrin is expected to be immobile in
soil(SRC). Volatilization of phenothrin from moist soil surfaces is expected to be an
important fate process(SRC) given an estimated Henry's Law constant of 6.80X10-6 atm-cu
m/mole(SRC), derived from its vapor pressure, 1.43X10-7 mm Hg(2), and water solubility,
9.70X10-3 mg/l(2). However, adsorption to soil is expected to attenuate
volatilization(SRC). Phenothrin is not expected to volatilize from dry soil surfaces(SRC)
based upon its vapor pressure(2). Although environmental biodegradation data specific to
phenothrin are not available, the pyrethroid class of insecticides is readily degraded by
environmental microorganisms(4,5); based upon its structure, phenothrin are also expected
to readily biodegrade(4,5). For example, residues of trans-phenothrin fell to <10 ppb
(initial concn unspecified) within 45 days in an aerobic soil(4). Residues of
trans-phenothrin remained close to 300 ppb (initial concn unspecified) after 60 days in an
anaerobic soil(4). Thus, degradation of phenothrin under anaerobic conditions is expected
to be slower than under aerobic conditions(SRC).
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of
56,000(SRC), determined from a water solubility of 9.70X10-3 mg/l(2) and a
regression-derived equation(3), indicates that phenothrin is expected to adsorb to
suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3)
based upon an estimated Henry's Law constant of 6.80X10-6 atm-cu m/mole(4) derived from
its vapor pressure, 1.43X10-7 mm Hg(2), and its water solubility(2). Using this Henry's
Law constant and an estimation method(3), volatilization half-lives for a model river and
model lake are 7 and 81 days, respectively(SRC). However, volatilization from water
surfaces is expected to be attenuated by adsorption to suspended solids and sediment in
the water column. The estimated volatilization half-life from a model pond is 1.47X10+4
years if adsorption is considered(4). According to a classification scheme(5), an
estimated BCF of 266(SRC), from an estimated log Kow and a regression-derived equation(6),
suggests the potential for bioconcentration in aquatic organisms is high(SRC). However,
bioconcentration studies on compounds which are structurally similar suggest that
bioconcentration may be lower than that indicated by the regression-derived equations due
to the ability of aquatic organisms to readily metabolize this class of compounds(7). A
base-catalyzed second-order hydrolysis rate constant of 4.02X10-2 l/mole-sec(SRC) was
estimated using a structure estimation method(8); this corresponds to half-lives of 5.5
years and 200 days at pH values of 7 and 8, respectively(8). Although environmental
biodegradation data specific to phenothrin are not available, the pyrethroid class of
insecticides is readily degraded by environmental microorganisms(7,9); based upon its
structure, phenothrin are also expected to readily biodegrade(7,9).
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile
organic compounds in the atmosphere(1), phenothrin, which has a vapor pressure of
1.43X10-7 mm Hg at 21 deg C(2), will exist in both the vapor and particulate phases in the
ambient atmosphere(SRC). Vapor-phase phenothrin is degraded in the atmosphere by reaction
with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in
air is estimated to be 4 hours(SRC), calculated from its rate constant of 1.06X10-10 cu
cm/molecule-sec at 25 deg C(SRC) determined using a structure estimation method(3).
Vapor-phase phenothrin is degraded in the atmosphere by reaction with
photochemically-produced ozone(SRC); the half-life for this reaction in air is estimated
to be 38 minutes(SRC), calculated from its rate constant of 4.30X10-16 cu cm/molecule-sec
at 25 deg C(SRC) determined using a structure estimation method(3). Particulate-phase
phenothrin may be removed from the air by wet and dry deposition(SRC). Pyrethrins, such as
phenothrin, undergo rapid decomposition primarily from UV-energized autooxidation (direct
reaction with atmospheric triplet oxygen)(4).
Environmental Biodegradation:
Although environmental biodegradation data specific to phenothrin are not available,
the pyrethroid class of insecticides is readily degraded by environmental
microorganisms(1,2); based upon its structure, phenothrin are also expected to readily
biodegrade(1,2). For example, residues of trans-phenothrin fell to <10 ppb within 45
days in an aerobic soil(2). Residues of trans-phenothrin remained close to 300 ppb
(initial concn unspecified) after 60 days in an anaerobic soil(2). Thus, degradation of
phenothrin under anaerobic conditions is expected to be slower than under aerobic
conditions(SRC).
Environmental Abiotic Degradation:
BOTH PHENOTHRIN ISOMERS (TRANS & CIS) WERE APPLIED TO WHEAT GRAIN CONTAINING 11%
MOISTURE AT RATE OF 4 PPM; LEVELS WERE MONITORED WHILE GRAIN WAS STORED IN DARK AT 15 OR
30 DEG C. BOTH ISOMERS DEGRADED SLOWLY, AFTER 12 MO, 79% & 97% REMAINED IN GRAIN
STORED AT 30 DEG C. BOTH ISOMERS WERE METABOLIZED THROUGH HYDROLYSIS OF ESTER LINKAGE, THE
OXIDATION OF BENZYL ALCOHOL TO BENZOIC ACID, & THE METHYLATION OF BENZOIC ACID.
The rate constant for the vapor-phase reaction of phenothrin with
photochemically-produced hydroxyl radicals has been estimated as 1.06X10-10 cu
cm/molecule-sec at 25 deg C(SRC) using a structure estimation method(1). This corresponds
to an atmospheric half-life of about 4 hours at an atmospheric concentration of 5X10+5
hydroxyl radicals per cu cm(1). The rate constant for the vapor-phase reaction of
phenothrin with ozone has been estimated as 4.30X10-16 cu cm/molecule-sec at 25 deg C(SRC)
using a structure estimation method(1). This corresponds to an atmospheric half-life of
about 38 minutes at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(2).
In addition, reaction with nitrate radicals may also be important(SRC). A base-catalyzed
second-order hydrolysis rate constant of 4.02X10-2 l/mole-sec(SRC) was estimated using a
structure estimation method(3); this corresponds to half-lives of 5.5 years and 200 days
at pH values of 7 and 8, respectively(3). Pyrethrins, such as phenothrin, undergo rapid
decomposition primarily from UV-energized autooxidation (direct reaction with atmospheric
triplet oxygen)(4).
Environmental Bioconcentration:
An estimated BCF of 266 was calculated for phenothrin(SRC), using an estimated log Kow
of 7.54(1) and a regression-derived equation(1). According to a classification scheme(2),
this BCF suggests the potential for bioconcentration in aquatic organisms is high(SRC).
However, bioconcentration studies on compounds which are structurally similar suggest that
bioconcentration may be lower than that indicated by the regression-derived equations due
to the ability of aquatic organisms to readily metabolize this class of compounds(3).
Soil Adsorption/Mobility:
The Koc of phenothrin is estimated as 56,000(SRC), using a water solubility of
9.70X10-3 mg/l(1) and a regression-derived equation(2). According to a classification
scheme(3), this estimated Koc value suggests that phenothrin is expected to be immobile in
soil(SRC).
Volatilization from Water/Soil:
The Henry's Law constant for phenothrin is estimated as 6.80X10-6 atm-cu m/mole(SRC)
based upon its vapor pressure, 1.43X10-7 mm Hg(1), and water solubility, 9.70X10-3
mg/l(1). This Henry's Law constant indicates that phenothrin 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 7 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 81 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 1.47X10+4 years if adsorption is considered(3). Phenothrin's estimated
Henry's Law constant(1) indicates that volatilization from moist soil surfaces may
occur(SRC). However, volatilization from water surfaces is expected to be attenuated by
adsorption to soil(SRC). Phenothrin is not expected to volatilize from dry soil
surfaces(SRC) based upon a vapor pressure of 1.43X10-7 mm Hg(1).
Food Survey Values:
RESIDUES OF PHENOTHRIN WERE HIGHLY PERSISTENT ON STORED WHEAT. DURING MILLING, RESIDUES
ACCUMULATED IN BRAN FRACTIONS & WERE REDUCED IN WHITE FLOUR. THEY WERE NOT
SIGNIFICANTLY REDUCED DURING BAKING.
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.
Phenothrin 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: 0426; 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): Phenothrin; 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.
Acceptable Daily Intakes:
FAO/WHO ADI: 0.07 mg/kg
OPP RfD= 0.071 mg/kg
Chemical/Physical Properties:
Molecular Formula:
C23-H26-O3
Molecular Weight:
350.46
Color/Form:
Colorless liquid
Pale yellow to yellow-brown clear liquid
Odor:
Faint characteristic odor
Boiling Point:
>290 deg C
Density/Specific Gravity:
1.06 @ 20 deg C
Solubilities:
In methanol, >5.0 g/ml; hexane, >4.96 g/ml @ 25 deg C.
In water, <9.7 ug/l @ 25 deg C.
Spectral Properties:
Index of refraction: 1.5483 @ 25 deg C/D
Vapor Pressure:
1.43X10-7 mm Hg @ 21 deg C
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:
Incompatible with alkaline materials.
... Incompatible with lime & ordinary soaps because acids & alkalies speed up
processes of hydrolysis. /Pyrethrins/
Hazardous Decomposition:
When heated to decomp it emits acrid smoke and fumes. /(+)-cis,trans-Phenothrin/
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/
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.
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.
Stability/Shelf Life:
STABLE UNDER IRRADIATION, IN MOST ORGANIC SOLVENTS & ON INORGANIC MINERAL DILUENTS
Hydrolyzed by alkalis
Pyrethrins ... /are/ stable for long periods in water-based aerosols where ...
emulsifiers give neutral water systems. /Pyrethrins/
Stable under normal storage conditions. ... Stable under u.v. irradiation.
Storage Conditions:
VENTILATE WELL. STORE IN CLOSED DRUM IN COOL, DRY PLACE.
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. ... /Pyrethrin
products/
Occupational Exposure Standards:
Manufacturing/Use Information:
Major Uses:
For Phenothrin (USEPA/OPP Pesticide Code: 26002-80-2) 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./
Insecticide for stored grain, sanitary uses, flying and crawling insect control, and
for industrial locations and outdoor use.
Used to control injurious and nuisance insects of public health.
MEDICATION
Anvil is a pesticide product that is used to control mosquitoes in outdoor residential
and recreational areas. It contains sumithrin /phenothrin/, piperonyl butoxide and
petroleum solvents. Sumethrin is a synthetic pesticide similar to a natural pesticide
(pyrethrum) produced by chrysanthemum flowers. ... Other pesticide products containing
these ingredients are used indoors and on pets to control insects such as fleas, ticks,
and ants.
Methods of Manufacturing:
3-Phenoxybenzyl alcohol + (1RS)-cis/trans-chrysanthemic acid (esterification)
General Manufacturing Information:
Non-systemic insecticide with contact and stomach action. ... used to control injurious
and nuisance insects of public health (Acari, Cimex lectularius, Culicidae, Miscidae,
Siphonaptera and Pediculus humanus). Also used to protect stored grain.
FOR SANITARY USES. CONTROLS HOUSEFLIES, MOSQUITOES, COCKROACHES, BEDBUGS, LICE &
FLEAS.
PHENOTHRIN HAS STRONG ACTIVITY AGAINST HEMIPTERA, LEPIDOPTERA, & DIPTERA, & WAS
HIGHLY EFFECTIVE AGAINST INSECTS RESISTANT TO CHLORINATED HYDROCARBONS, ORGANOPHOSPHATES
& CARBAMATES.
PHENOTHRIN APPLIED TO WHEAT STORED FOR 52 WK HAD HALF-LIFE OF 72 & 29 WK AT 25 DEG
C (12% MOISTURE) & 35 DEG C (15% MOISTURE).
The commercial product is a mixture of isomers.
Potent synthetic pyrethroid insecticide.
Compatible with other insecticides, especially pyrethroids.
The technical product exists as the (1R)-cis, trans isomeric mixture. /Technical
phenothrin/
/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 069005; Trade Names: Forte, Phenothrin (26002-80-2),
Phenoxythrin, S-2539, Sumithrin, Phenothrin, Fenothrin.
Emulsifiable concentrate, aerosol, oil liquid, and powder.
A SYNERGISTIC INSECTICIDE COMPOSITION FOR CONTROL OF STORED-PRODUCT PESTS INCLUDE
PHENOTHRIN 0.2, FENITROTHION 20, PIPERONYL BUTOXIDE 0.4, ANTIOXIDANT 20, WETTING AGENT
0.5, DISPERSING AGENT 1, & DIATOMACEOUS EARTH 57.9% IN A WETTABLE POWDER.
Mixed formulations: (d-phenothrin +) allethrin; piperonyl butoxide; tetramethrin;
allethrin + piperonyl butoxide; piperonyl butoxide + tetramethrin.
Anvil is a pesticide product that is used to control mosquitoes ... contains sumithrin,
piperonyl butoxide and petroleum solvents.
Pyrethroids are formulated as emulsifiable concentrates, wettable powders, granules,
and concentrates for ultra low volume application. /Pyrethroids/
Laboratory Methods:
Analytic Laboratory Methods:
GAS CHROMATOGRAPHIC & HIGH PERFORMANCE LIQUID CHROMATOGRAPHIC METHODS WERE
DEVELOPED FOR DETERMINATION OF SYNTHETIC PYRETHOIDS (INCL PHENOTHRIN) IN FORMULATED
PRODUCTS.
METHODS OF EXTRACTION & ANALYSIS SUITED FOR ANALYSIS OF AGED, UNKNOWN RESIDUES ON
WHEAT, BARLEY, OATS, SORGHUM, RICE IN HUSK, MILLED RICE, POLISHED RICE & COOKED RICE
ARE REPORTED FOR PYRETHROIDS (INCL PHENOTHRIN & D-PHENOTHRIN). PYRETHROIDS, AFTER
ALKALINE HYDROLYSIS, WERE DETERMINED COLORIMETRICALLY FROM REACTION OF CHRYSANTHEMIC ACID
WITH ACIDIFIED MERCURY (II) SULFATE.
GAS CHROMATOGRAPHY USED FOR ANALYSIS OF PYRETHROID RESIDUES (INCL PHENOTHRIN) IN
VEGETABLES & FRUITS.
EPA Method 1660. The Determination of Pyrethrins and Pyrethroids in Municipal and
Industrial Wastewater by High-Performance Liquid Chromatography. Detection limit = 1 ug/l.
Special References:
Special Reports:
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 insecticides 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-2539
**PEER REVIEWED**
CYCLOPROPANECARBOXYLIC ACID, 2,2-DIMETHYL-3-(2-METHYLPROPENYL)-, M-PHENOXYBENZYL ESTER,
(+)-(Z,E)-
**PEER REVIEWED**
CYCLOPROPANECARBOXYLIC ACID, 2,2-DIMETHYL-3-(2-METHYLPROPENYL)-, M-PHENOXYBENZYL ESTER
**PEER REVIEWED**
CYCLOPROPANECARBOXYLIC ACID, 2,2-DIMETHYL-3-(2-METHYL-1-PROPENYL)-,
(3-PHENOXYPHENYL)METHYL ESTER
**PEER REVIEWED**
3-PHENOXYBENZYL
(1RS)-CIS,TRANS-2,2-DIMETHYL-3-(2-METHYLPROP-1-ENYL)CYCLOPROPANECARBOXYLATE
**PEER REVIEWED**
2,2-dimethyl-3-(2-methylpropenyl)cyclopropanecarboxylic acid m-phenoxybenzyl ester
**PEER REVIEWED**
2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylic acid (3-phenoxyphenyl)methyl
ester
**PEER REVIEWED**
ENT 27 972
**PEER REVIEWED**
Pesticide Code: 069005
**PEER REVIEWED**
(+)-TRANS,CIS-FENOTHRIN
**PEER REVIEWED**
Multicide Concentrate F-2271
**PEER REVIEWED**
OMS 1810
**PEER REVIEWED**
(+)-CIS,TRANS-PHENOTHRIN
**PEER REVIEWED**
Phenothrine
**PEER REVIEWED**
3-PHENOXYBENZYL CIS,TRANS-CHRYSANTHEMATE
**PEER REVIEWED**
3-phenoxybenzyl (+-)-cis-trans-chrysanthemate
**PEER REVIEWED**
3-PHENOXYBENZYL (1RS)-CIS,TRANS-CHRYSANTHEMATE
**PEER REVIEWED**
3-phenoxybenzyl (1RS, 3RS; 1RS, 3SR)-2,2-dimethyl-3-(2-methylprop-1-enyl)
cyclopropanecarboxylate.
**PEER REVIEWED**
m-phenoxybenzyl 2,2-dimethyl-3-(2-methylpropenyl)cyclopropanecarboxylate
**PEER REVIEWED**
3-phenoxybenzyl 2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropanecarboxylate
**PEER REVIEWED**
(3-PHENOXYPHENYL)METHYL 2,2-DIMETHYL-3-(2-METHYL-1-PROPENYL)CYCLOPROPANECARBOXYLATE
**PEER REVIEWED**
(3-PHENOXYPHENYL)METHYL 2,2-DIMETHYL-3-(2-METHYL-1-PROPENYL)CYCLOPROPANE- CARBOXYLATE
**PEER REVIEWED**
PHENOXYTHRIN
**PEER REVIEWED**
SUMETHRIN
**PEER REVIEWED**
SUMITHRIN
**PEER REVIEWED**
SUMITRIN
**PEER REVIEWED**
Formulations/Preparations:
USEPA/OPP Pesticide Code 069005; Trade Names: Forte, Phenothrin (26002-80-2),
Phenoxythrin, S-2539, Sumithrin, Phenothrin, Fenothrin.
Emulsifiable concentrate, aerosol, oil liquid, and powder.
A SYNERGISTIC INSECTICIDE COMPOSITION FOR CONTROL OF STORED-PRODUCT PESTS INCLUDE
PHENOTHRIN 0.2, FENITROTHION 20, PIPERONYL BUTOXIDE 0.4, ANTIOXIDANT 20, WETTING AGENT
0.5, DISPERSING AGENT 1, & DIATOMACEOUS EARTH 57.9% IN A WETTABLE POWDER.
Mixed formulations: (d-phenothrin +) allethrin; piperonyl butoxide; tetramethrin;
allethrin + piperonyl butoxide; piperonyl butoxide + tetramethrin.
Anvil is a pesticide product that is used to control mosquitoes ... contains sumithrin,
piperonyl butoxide and petroleum solvents.
Pyrethroids are formulated as emulsifiable concentrates, wettable powders, granules,
and concentrates for ultra low volume application. /Pyrethroids/
RTECS Number:
NIOSH/GZ1975000
Administrative Information:
Hazardous Substances Databank Number: 3922
Last Revision Date: 20011010
Last Review Date: Reviewed by SRP on 5/10/2001
Update History:
Complete Update on 10/10/2001, 45 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 07/24/2000, 2 fields 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 06/02/1998, 1 field added/edited/deleted.
Complete Update on 10/31/1997, 1 field added/edited/deleted.
Complete Update on 05/09/1997, 1 field added/edited/deleted.
Complete Update on 04/23/1997, 2 fields added/edited/deleted.
Complete Update on 03/11/1997, 1 field added/edited/deleted.
Complete Update on 10/18/1996, 1 field added/edited/deleted.
Complete Update on 05/13/1996, 1 field added/edited/deleted.
Complete Update on 03/25/1996, 29 fields added/edited/deleted.
Field Update on 01/27/1996, 1 field added/edited/deleted.
Complete Update on 12/30/1994, 1 field added/edited/deleted.
Complete Update on 11/28/1994, 1 field added/edited/deleted.
Complete Update on 03/25/1994, 1 field added/edited/deleted.
Complete Update on 03/01/1994, 48 fields added/edited/deleted.
Field update on 12/31/1992, 1 field added/edited/deleted.
Field update on 11/09/1990, 1 field added/edited/deleted.
Field update on 03/06/1990, 1 field added/edited/deleted.
Complete Update on 10/03/1986
Record Length: 129178