Cancer
PBO is classified as a Group C-possible
human carcinogen with no cancer quantification required
for PBO risk assessments. In a combined chronic/carcinogenic study
in rats, positive carcinogenic effects were reported at doses where
a high incidence of ileocecal ulcers were noticed in test mammals.
Liver adenomas and carcinomas were reported in Fischer 344 rats only
when tested at very high doses. A slight increase in thyroid
follicular cell tumors was reported in Sprague-Dawley rats. A 1979
National Toxicology Program (NTP) study reported negative effects
for carcinogenicity in the same strain of rats and in B6C3F1 mice.
In CD-1 mice, PBO tested positive for liver tumor effects.
2006 USEPA
No data are available in humans. Inadequate evidence of
carcinogenicity in animals. OVERALL EVALUATION: Group 3: The agent
is not classifiable as to its carcinogenicity to humans.
Human Toxicity Excerpts:
A single oral dose of 50 mg (about 0.71 mg/kg body weight)
piperonyl butoxide given to adult volunteers did
not influence the metabolism of antipyrine, and no sign of toxicity
was recorded.
There have been sporadic reports indicating a possible
association between pesticide exposure and adverse respiratory
effects ... . In Hawaii, blind follow-up of 1% random sample of
people on Oahu showed a correlation between reported household
pesticide use and the occurrence of both asthma and respiratory
impairment as measured by /spirometry/ was stronger when cigarette
smokers were excluded. The most commonly used agent was a
combination of pyrethrum, ... piperonyl butoxide,
and petroleum distillates. ...
Skin, Eye and Respiratory Irritations:
Tests on eyes and skin of rabbits, rats, cats, and dogs showed
that it was not damaging, although it may be irritating.
Probable Routes of Human Exposure:
Occupational exposure to piperonyl butoxide may
occur through inhalation and dermal contact with this compound at
workplaces where piperonyl butoxide is produced or
used. The general population may be exposed to piperonyl
butoxide via ingestion of food products containing
piperonyl butoxide. The general population may also be
exposed to piperonyl butoxide through the use of
insecticides containing this compound. (SRC)
Minimum Fatal Dose Level:
2. 2= SLIGHTLY TOXIC: PROBABLE ORAL LETHAL DOSE (HUMAN) 5-15
G/KG, BETWEEN 1 PINT & 1 QUART FOR A 70 KG PERSON (150 LB).
Emergency Medical Treatment:
Emergency Medical Treatment:
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The following Overview, *** PIPERONYL BUTOXIDE ***,
is relevant for this HSDB record chemical.
Life Support:
o This overview assumes that basic life support measures
have been instituted.
Clinical Effects:
0.2.1 SUMMARY OF EXPOSURE
0.2.1.1 ACUTE EXPOSURE
A) Piperonyl butoxide is minimally toxic. Acute oral or
dermal exposure is UNLIKELY to result in significant
signs and symptoms of systemic toxicity or dermal
irritation. This chemical is often combined with
hydrocarbons or other insecticides that may require
treatment.
B) The MINIMAL TOXIC OR LETHAL DOSE is not established.
C) PHARMACOLOGIC EFFECT - Piperonyl butoxide inhibits
mixed function oxidase enzymes of the liver which
metabolize pyrethrins and pyrethroids, with which they
are combined.
0.2.4 HEENT
0.2.4.1 ACUTE EXPOSURE
A) Piperonyl butoxide may cause eye irritation, but is not
damaging.
0.2.7 NEUROLOGIC
0.2.7.1 ACUTE EXPOSURE
A) One case of pathological laughter has been reported
with human exposure. Primary sources of data are from
animals which include reports of hyperexcitability,
unsteadiness, coma, seizures, and brain damage in large
overdoses.
0.2.8 GASTROINTESTINAL
0.2.8.1 ACUTE EXPOSURE
A) Nausea, vomiting, anorexia, or diarrhea may be seen.
0.2.9 HEPATIC
0.2.9.1 ACUTE EXPOSURE
A) Hepatic changes and liver injury have been seen with
large doses given to various animal species.
0.2.13 HEMATOLOGIC
0.2.13.1 ACUTE EXPOSURE
A) Various anemias have been reported in animal studies.
0.2.14 DERMATOLOGIC
0.2.14.1 ACUTE EXPOSURE
A) Skin irritation or significant percutaneous absorption
is not expected following normal dermal exposure.
0.2.17 METABOLISM
0.2.17.1 ACUTE EXPOSURE
A) Animal studies have shown elevated metabolic enzymes
after ingestion of this compound.
0.2.20 REPRODUCTIVE HAZARDS
A) Mixed results for teratogenicity have been obtained in
animals.
0.2.21 CARCINOGENICITY
0.2.21.1 IARC CATEGORY
A) IARC Carcinogenicity Ratings for CAS51-03-6 (IARC,
2004):
1) IARC Classification
a) Listed as: Piperonyl butoxide
b) Carcinogen Rating: 3
1) The agent (mixture or exposure circumstance) is not
classifiable as to its carcinogenicity to humans.
This category is used most commonly for agents,
mixtures and exposure circumstances for which the
evidence of carcinogenicity is inadequate in humans
and inadequate or limited in experimental animals.
Exceptionally, agents (mixtures) for which the
evidence of carcinogenicity is inadequate in humans
but sufficient in experimental animals may be placed
in this category when there is strong evidence that
the mechanism of carcinogenicity in experimental
animals does not operate in humans. Agents, mixtures
and exposure circumstances that do not fall into any
other group are also placed in this category.
0.2.21.2 HUMAN OVERVIEW
A) At the time of this review, no studies were found on
the possible carcinogenic activity of piperonyl
butoxide in humans.
0.2.22 GENOTOXICITY
A) At the time of this review, no data were available to
assess the mutagenic or genotoxic potential of this
agent.
Laboratory:
A) PIPERONYL BUTOXIDE LEVELS are not clinically useful.
B) No specific lab work is needed unless otherwise indicated
by the patient's condition.
Treatment Overview:
0.4.2 ORAL EXPOSURE
A) Piperonyl butoxide is of low toxicity. Gastric
decontamination is only indicated if there is a
coingestant with significant toxicity.
B) GASTRIC LAVAGE: Consider after ingestion of a
potentially life-threatening amount of poison if it can
be performed soon after ingestion (generally within 1
hour). Protect airway by placement in Trendelenburg and
left lateral decubitus position or by endotracheal
intubation. Control any seizures first.
1) CONTRAINDICATIONS: Loss of airway protective reflexes
or decreased level of consciousness in unintubated
patients; following ingestion of corrosives;
hydrocarbons (high aspiration potential); patients at
risk of hemorrhage or gastrointestinal perforation; and
trivial or non-toxic ingestion.
C) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240
mL water/30 g charcoal). Usual dose: 25 to 100 g in
adults/adolescents, 25 to 50 g in children (1 to 12
years), and 1 g/kg in infants less than 1 year old.
D) NATIONAL PESTICIDE HOTLINE -
1) The National Pesticide Information Center (NPIC) is a
cooperative effort of Oregon State University and the
US EPA. NPIC provides consultation to poison centers
and other health care professionals for the management
of pesticide poisoning. Calls regarding emergency cases
requiring immediate medical response will be
transferred to the Oregon Poison Center.
a) NPIC contact information: phone: 1-800-858-7378;
(outside the U.S. 541-737-6094). FAX: 1-541-737-0761.
email: npic@ace.orst.edu Hours: 6:30 AM to 4:30 PM
Pacific time 7 days/week excluding holidays.
0.4.3 INHALATION EXPOSURE
A) 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 inhaled
beta2 agonist and oral or parenteral corticosteroids.
0.4.4 EYE EXPOSURE
A) DECONTAMINATION: Irrigate exposed eyes with copious
amounts of room temperature water for at least 15
minutes. If irritation, pain, swelling, lacrimation, or
photophobia persist, the patient should be seen in a
health care facility.
0.4.5 DERMAL EXPOSURE
A) OVERVIEW
1) 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.
Range of Toxicity:
A) Minimally toxic, specific toxic dose not determined.
There have been no human deaths reported due to acute
exposure. No irritation or toxic effects have been
observed after dermal contact.
B) Male volunteers tolerated a single oral dose of 50 mg
(0.71 mg/kg body weight) piperonyl butoxide with no signs
of toxicity.
Antidote and Emergency Treatment:
Basic treatment: Establish a patent airway. Suction if necessary.
Watch for signs of respiratory insufficiency and assist ventilations
if needed. Administer oxygen by nonrebreather mask at 10 to 15
L/min. Monitor for pulmonary edema and treat if necessary ... .
Monitor for shock and treat if necessary ... . 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 ... . Cover skin burns with dry sterile dressings
after decontamination ... . /Poison A and B/
Advanced treatment: Consider orotracheal or nasotracheal
intubation for airway control in the patient who is unconscious, has
severe pulmonary edema, or is in respiratory arrest. Positive
pressure ventilation techniques with a bag valve mask device may be
beneficial. Monitor cardiac rhythm and treat arrhythmias as
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. Consider drug therapy
for pulmonary edema ... . For hypotension with signs of hypovolemia,
administer fluid cautiously. Watch for signs of fluid overload ... .
Treat seizures with diazepam (Valium) ... . Use proparacaine
hydrochloride to assist eye irrigation ... . /Poison A and B/
Antihistamines are effective in controlling most allergic
reactions. Severe asthmatic reactions, particularly in predisposed
persons, may require administration of inhaled B2-agonists and/or
systemic corticosteroids. Inhalation exposure should be carefully
avoided in the future. /Pyrethrum and pyrethrins/
Anaphylaxis-type reactions may require subcutaneous epinephrine,
epinephrine, and respiratory support. /Pyrethrum and pyrethrins/
Contact dermatitis may require extended administration of topical
corticosteroid preparations. This should be done under the
supervision of a physician. Future contact with the allergen must be
avoided. /Pyrethrum and pyrethrins/
Other toxic manifestations caused by other ingredients must be
treated according to their respective toxic actions, independent of
pyrethrin-related effects. /Pyrethrum and pyrethrins/
Gastrointestinal decontamination. Even though most ingestions of
pyrethrin products present little risk, if a large amount of
pyrethrin-containing material has been ingested and the patient is
seen within one hour, consider gastric emptying. If the patient is
seen later, or if gastric emptying is performed, consider
administration of activated charcoal ... . /Pyrethrum and
pyrethrins/
Animal Toxicity Studies:
Evidence for Carcinogenicity:
No data are available in humans. Inadequate evidence of
carcinogenicity in animals. OVERALL EVALUATION: Group 3: The agent
is not classifiable as to its carcinogenicity to humans.
Non-Human Toxicity Excerpts:
PIPERONYL BUTOXIDE STIMULATED HEPATIC ALA
(DELTA-AMINOLEVULINIC ACID) SYNTHETASE ACTIVITY IN MICE.
NO MUTAGENIC ACTIVITY WAS DETECTED IN SPOT TESTS OF SALMONELLA
TYPHIMURIUM STRAINS TA 1537, TA 98, & TA 100 WITH & WITHOUT LIVER
MICROSOMAL ACTIVATION.
PREGNANT ALBINO RATS WERE TREATED BY GAVAGE WITH EITHER 300 OR
1000 MG/KG FROM DAY 6 TO 15 OF GESTATION. PIPERONYL BUTOXIDE
WAS FOUND NOT TO BE TERATOGENIC AT LEVELS BELOW THOSE THAT
ARE TOXIC TO DAMS.
DIETARY LEVEL OF 10,000 PPM, WHICH PRODUCED ABOUT 22% FOOD
REFUSAL COMPARED WITH THAT OF CONTROLS & THEREFORE A DOSAGE OF 650
MG/KG/DAY, LED TO MODERATE REDUCTION OF WT GAIN, INCREASED RELATIVE
WT OF KIDNEYS IN SOME EXPERIMENTS, INCREASED RELATIVE WT OF LIVER IN
ALL EXPERIMENTS, & DECREASED REPRODUCTION (AVG DELAY OF OVER 23 DAYS
TO 1ST LITTER, REDUCED AVG NUMBER OF LITTERS/FEMALE, REDUCED AVG WT
OF YOUNG/LITTER AT 4 WEEKS OF AGE, & TREND TO SMALLER NUMBER OF
YOUNG/LITTER). /ORAL, RATS/
Piperonyl butoxide was tested alone and as an
anticarcinogenic agent for N-Nitrosodiethylamine induced lung and
trachea tumors in hamsters. Nine wk old Syrian hamsters, NCI: (syr),
were divided into the following 5 groups of 10 aninmals: 1) 0.1 ml
0.9% NaC1; 2) 17.8 mg/kg N-nitrosodiethylamine in 0.9 NaC1, 0.1 ml;
3) 400 mg/kg piperonyl butoxide in sesame oil, 0.2
ml, 2 hours before 17.8 mg/kg N-nitrosodiethylamine in 0.9 NaC1, 0.1
ml; 4) 400 mg/kg piperonyl butoxide in sesame oil,
0.2 ml; and 5) 0.2 ml sesame oil, all injections were subcutaneous
and given twice per week for 20 weeks when all groups were
autopsied. There was no difference in growth rate and no mortality
in any group. Lung and trachea were examined both histologically and
with the electron microscope. There were no tumors of lung or
trachea induced in groups 1, 4, or 5 (confirmed with electron
microscopy). There were 6 animals out of 10 in the piperonyl
butoxide-N-nitrosodiethylamine-only treated animals (group
2) and 0 out of 10 animals in the piperonyl butoxide-N-nitrosodiethylamine
treated animals (group 3) with lung tumors. There were 10 out of 10
animals in the N-nitrosodiethylamine-only treated animals (group 2),
and 5 out of 10 animals in the piperonyl butoxide-N-nitrosodiethylamine
treated animals (group 3) with tracheal tumors. While showing no
carcinogenic effect itself under these conditions, completely
inhibited N-nitrosodiethylamine-induced pulmonary carcinogenesis and
reduced the incidence of tracheal tumors by 50%, this effect is
significant (P<.01).
Piperonyl butoxide induced ileocaecal mucosa
ulcers at a high incidence but was not found to be carcinogenic
after a 2-year dietary study in F344/DuCrj rats. From 6 weeks of
age, 50 rats of each sex were given a powdered basal diet mixed with
2% corn oil and either 0%, 0.5%, or 1% piperonyl butoxide
for 104 weeks. Moribund or dead animals and all survivors
at 110 weeks were autopsied and examined histologically. Various
tumors were detected in all groups including the untreated controls,
but no significant dose-related increase in the incidence of any
tumor was found. Growth curves were depressed. Cumulative deaths
were 16% (controls), 38% (0.5% piperonyl butoxide),
and 42% (1% piperonyl butoxide) in males; 14%
(controls), 22% (0.5% piperonyl butoxide), and 34%
(1% piperonyl butoxide) in females. Differences
were found between the controls and the treated groups of rats for
ileocaecal ulcers of 0/48 (0% piperonyl butoxide),
17/48 (0.5% piperonyl butoxide), and 24/46 (1%
piperonyl butoxide) for males, and 0/47 (0%
piperonyl butoxide), 1/49 (0.5% piperonyl
butoxide), and 22/49 (1% piperonyl butoxide)
for females. In males given 0.5% piperonyl butoxide
and in both sexes given 1% piperonyl butoxide,
these differences were statistically significant compared
to the controls (P<0.01).
Piperonyl butoxide, like other methylene
dioxybenzene synergists ... , inhibits hepatic microsomal oxidase
enzymes in laboratory rodents and by inference in man; it also
inhibits a related group of enzymes in insects, apparently by
serving as a competitive substrate.
A single large oral dose produces anorexia, unsteadiness, rough
coat, watering eyes, irritability, prostration, coma, and death.
Onset may be as early as 20 minutes after dosing. Illness may last
several days, and death may be delayed as much as 1 week. The signs
are similar but are delayed, following a small number of repeated
doses sufficient to produce death. Repeated doses that kill rats
only after several or many weeks produce anorexia, stunting, and
cachexia. Dogs react in a similar way but also vomit.
Undiluted piperonyl butoxide is mildly
irritating to rabbit skin on repeated application, but it is not
sensitizing.
The acute oral toxicity of piperonyl butoxide is
low. The compound is even less toxic to rats when injected
subcutaneously, presumably because of poor absorption. A spray
concentrate containing unusually high proportions of
piperonyl butoxide (20%) and pyrethrins (2.5%) was found to
be little, if any more, toxic for rats than the petroleum oil
solvent alone.
A goat tolerated about 66 mg/kg/day for a year without clinical
effect. During that period, she successfully nursed a kid. At
autopsy the liver of the mother showed minimal change, but that of
the kid was entirely normal.
African green monkeys tolerated piperonyl butoxide
better than dogs at doses as high as 105 mg/kg/day, but the
monkeys received only 24 doses, rather than a year of treatment.
Groups of 18 male and 18 female (C57BL/6 X C3H/Anf)F mice and 18
male and 18 female (C57BL/6 X AKR)F mice received piperonyl
butoxide (80% pure) according to the following schedule:
100 mg/kg body weight in 0.5% gelatin at seven days of age by
stomach tube and the same amount (not adjusted for increasing body
weight) daily up to four weeks of age; subsequently, the mice were
fed 300 mg/kg of diet. (The dose was the maximum tolerated dose for
infant and young mice but not necessarily that for adults.) The
experiment was terminated at 70 weeks of age, when all animals were
killed. Tumor incidences were compared with those in 79-90
necropsied mice of each sex and strain, which had either been
untreated or had received gelatine only. No significant difference
in the incidence of tumors was found between treated and control
mice.
Rabbits generally survive a single dermal application at the rate
of 1880 mg/kg in the form of a 20% solution in dimethyl phthalate;
it causes no skin irritation but does cause hyperexcitability and
convulsions ... .
Dogs showed a progressive increase in liver weight associated
with dosage rates of 3, 31, 105, and 315 mg/kg/day. Dosages of 105
and 315 mg/kg/day produced weight loss; morphological changes in the
liver, kidney, and adrenal gland; and at the higher level, death of
all animals in 4-15 weeks attributed to liver injury ... . The death
of one dog that received 31 mg/kg/day was attributed to natural
causes but involved severe, unexplained liver injury ... .
Groups of 50 male and 50 female B6C3F mice, six weeks of age,
were fed diets containing piperonyl butoxide (technical
grade; purity 88.4%; containing 2.1% butyl carbinol, 2.4% of an
isomer of piperonyl butoxide and several minor
contaminants) as follows: the low-dose group received 2,500 mg/kg of
diet for 30 weeks and 2,000 mg/kg for an additional 82 weeks
(time-weighted average dose, 2,804 mg/kg of diet). All surviving
animals were killed at 112 weeks. A matched control group consisted
of 20 male and 20 female mice. Although variations in tumor
incidence were observed, no significant difference attributable to
treatment was found for any tumor type.
Groups of 50 male and 50 female Fischer 344 rats, six weeks old,
were fed ad libitum diets containing either 5,000 or 10,000 mg/kg
piperonyl butoxide (technical grade; purity 88.4%;
containing 2.1% butyl carbinol, 2.4% piperonyl butoxide
isomer and several minor contaminants) for 107 weeks.
Matched controls consisted of 20 untreated rats of each sex. All
surviving rats were killed at 107 weeks. Of the treated females,
7/30 in the low-dose group and 15/50 in the high-dose group (p =
0.02) developed lymphomas, compared with 1/20 matched controls
(Although these tumors occurred at incidences that were dose related
(p = 0.007), the validity of the results was considered questionable
in view of the high incidence of lymphomas and leukemias in
historical female controls of that strain (0-32%). No significant
difference attributable to treatment was found for any tumor type in
male rats.
Groups of 18 male and 18 female (C57BL/6 x C3H/Anf)F mice and 18
male and 18 female (C57BL/6 x AKR)F mice were given single sc
injections of 1,000 mg/kg body weight piperonyl butoxide
as Butacide in corn oil on the 28th day of
life and were observed until they were about 78 weeks of age, at
which time almost all mice were still alive. A group of negative
controls comprised untreated animals and animals treated with
gelatine, corn oil or dimethyl sulfoxide. No significant difference
in tumor incidence was observed.
In a reproductive study, groups of 12 male and 12 female Wistar
rats, four weeks of age, were fed piperonyl butoxide (technical
grade; 80% pure; impurities undefined) at concentrations of 100,
1,000, 10,000 or 25,000 mg/kg of diet for up to 104 weeks. A group
of 12 male and 12 female rats served as controls. Male and female
rats from the corresponding groups were paired to assess
reproductive efficacy. By 68 weeks, all of the rats fed the highest
dose had died, presumably due to liver damage. A few tumors were
found in the liver and lymphoid system in similar incidences in
treated and non-treated groups.
Groups of 18 male and 18 female (C57BL/6 x C3H/Anf)F mice and 18
male and 18 female (C57BL/6 x AKR)F mice were given single sc
injections of 100 mg/kg body weight piperonyl butoxide (80%
pure) in corn oil on the 28th day of life and were observed until
they were about 78 weeks of age, at which time 17, 16, 17 and 18
mice were still alive in the four groups, respectively. A group of
negative controls comprised untreated animals and animals treated
with gelatine, corn oil or dimethyl sulfoxide. No increased
incidence in tumor incidence was observed between treated and
control animals.
The toxicity of piperonyl butoxide in ICR mice
was investigated. Male and female mice were allowed free access to
diets containing 0, 0.1, 0.3, or 0.9% piperonyl butoxide
for 20 days. These dose levels corresponded to 0, 1,000,
3,000, or 9,000 ppm. Food consumption was reduced ln the 0.9% group,
especially during the first 3 days. Dietary intake of 0.9%
piperonyl butoxide for 20 days produced liver damage in
male and female ICR mice as demonstrated in increased liver weights,
elevated levels of serum cholesterol, total protein and
gamma-glutamyl-transpeptidase. Macroscopic hepatomegaly was marked
in the 0.3 and 0.9% groups. The livers of all mice in the 0.9% group
showed enlarged hepatocytes with glassy basophilic cytoplasm, mild
anisonucleosis, an incr in multinucleated cells, single cell
necrosis, and cell infiltration in the centrilobular area of the
liver. The dietary concn that caused liver damage in ICR mice, 0.3%,
by 20 days was one quarter of that required in F344 rats by 13 weeks
of dosing in a previous study. These findings indicated that ICR
mice may be more sensitive to piperonyl butoxide
with respect to hepatotoxic effects than F344 rats. Significant decr
in kidney weight were noted in male and female mice of the 0.9%
group, but no other evidence for kidney damage was noted.
Liver and kidney changes were investigated in male F344/Ducrj
rats fed diets containing 0.6%, 1.2%, or 2.4% piperonyl
butoxide for 1, 2, 4 or 12 weeks. Rats were sacrificed at
the conclusion of the experimental period. ... Kidneys and livers
were examined histologically. Body weights were depressed in a dose
dependent manner. Absolute and relative liver weights of treated
rats were significantly higher that those of the corresponding
control group. Pathological changes were seen in the livers and
kidneys. Liver changes included oval cell proliferation, bile duct
hyperplasia, single cell necrosis, enlargement of hepatocytes,
enlargement of hepatocyte nuclei, and anisonucleosis in rats in the
1.2 and 2.4% groups. In the 2.4% group, multivesiculated vacuoles
were seen the hepatocytes in the periportal area. No pathological
changes were observed in the kidneys at 1 or 2 weeks after starting
the study, while serum urea nitrogen levels were increased from 1
week in the 2.4% group. At 12 weeks atrophy and deposition of yellow
brown pigment in the proximal tubules, dilation of tubules, cell
infiltration and fibrosis appeared in all treated groups. /Results/
suggest that subacute effects of piperonyl butoxide
were greater in the liver than in the kidney.
Piperonyl butoxide was tested for teratogenicity
using ICR mice. Piperonyl butoxide suspended in
olive oil was given orally to pregnant mice at days 7-15, or day 9
of gestation. All fetuses were removed from the uterus on day 18 of
gestation, and were examined for external and skeletal anomalies. In
mice given 150, 300 or 600 mg piperonyl butoxide/kg
body weight/day on days 7-15 of gestation, no external and skeletal
anomalies directly related to /this cmpd/ were observed. In mice
given one of 7 doses of piperonyl butoxide (1,000-5,000
mg/kg) on day 9 of gestation, reduction deformity of limbs
especially the reduction of digit V in the right and left forelimb,
was found. The number of litters having fetuses with reduction
deformity of limbs and of those having fetuses with skeletal fusion
increased in proportion to the dose of piperonyl butoxide.
The regression lines of Y (probit response) on X (log dose)
for reduction deformity of limbs and for skeletal fusion were Y =
7.8X - 4.3 and Y = 4.6X - 1.1, respectively. The effective doses
(ED1) for the two malformations were 700 and 660 mg/kg,
respectively.
Piperonyl butoxide was administered to pregnant
mice by gavage at a level of 0 (control), 1065, 1385 and 1800 mg/kg
body weight only on day 9 of gestation. The animals were sacrificed
on day 18 of gestation. Early and late fetal deaths were
significantly increased in the higher dose groups and those effects
were significantly dose related. The average body weights of male
and female fetuses were significantly reduced in a dose related
fashion. The external malformation of oligodactyly in forelimbs was
significantly incr in higher treatment groups in a dose related
manner. The dose levels of piperonyl butoxide in
the present study produced adverse effects on developmental
parameters.
Piperonyl butoxide was admin continuously to
mice from 5 weeks of age in the F0 generation to weanling of the F2
generation. Piperonyl butoxide was admin in the
diet at levels of 0 (control), 0.1, 0.2, 0.4 and 0.8%. Selected
reproductive developmental and behavioral parameters were measured.
Litter size and litter weight were reduced in higher dosed groups
and the body weight of the pups in the lactation period was reduced
in dosed pups in each generation. The survival index at postnatal
day 21 of the group receiving 0.8% piperonyl butoxide
was reduced in each generation. The developmental and
behavioral parameters in the lactation period were little different
from those of the controls apart from olfactory orientation in the
F1 generation. However in the F2 generation mice, surface righting,
cliff avoidance and olfactory orientation were adversely affected in
treatment groups. The results suggest that piperonyl
butoxide had adverse effects on reproductive developmental
and behavioral parameters of mice with increasing effects in
subsequent generations of offspring.
The ability of piperonyl butoxide to induce
hepatocellular carcinoma in male mice was assessed. Male CD-l mice
were placed in groups of 52, 52 and 100, and given diets containing
piperonyl butoxide at levels of 0, 0.6%, and 1.2%.
Daily clinical signs and mortality were recorded, and dead mice were
examined histopathologically with hematoxylin and eosin for tumors
and nonneoplastic lesions. After 12 months, surviving mice were
sacrificed and examined histopathologically as before in liver. The
results indicated that most lethalities occurred after 6 months, and
11 of the 1.2% group died between 9.5 and 12 months. Most of the
dead and surviving mice treated had single or multiple nodules in
all lobes of the liver. The number and sizes of nodules were greater
in the 1.2% group. Hepatocellular adenomas and carcinomas were
increased in a dose related manner, with an incr of five fold after
a doubling in dose. /Results suggest/ that piperonyl
butoxide can induce hepatocellular carcinoma in mice as
well as in rats.
Male and female F344 rats (30-33 rats/group) were admin
piperonyl butoxide at levels of 0 (control), 0.6, 1.2, and
2.4% for nearly 2 years. Beginning at about 40 weeks, 10 rats ln the
1.2% treated male group died due to cecal hemorrhages.
Piperonyl butoxide induced hepatocellular carcinoma in both
sexes in a dose dependent manner. Hepatocellular carcinoma was found
even in the 1.2% treated male group (incidence, 26.7%), and
incidence in the 2.4% groups of males and females were 80.0 and
57.7% respectively of all those surviving. Piperonyl
butoxide also caused essential thrombocythemia with a dose
response relationship. Hemorrhages in stomach and cecum, anemia,
degenerative lesions of alveoli, and nephrotoxicity were also
observed related to exposure. These results indicate that
piperonyl butoxide is a hepatocarcinogenic to the rat.
Piperonyl butoxide ... inhibits
dimethylnitrosamine demethylase involved on dimethylnitrosamine
activation. Short term exposure to piperonyl butoxide (640
mg/kg) decr dimethylnitrosamine mutagenicity, but effects on
macromolecular alkylation by dimethylnitrosamine are controversial.
Groups of 4 six wk old female CBA mice were given a single ip
injection of 600 mg/kg piperonyl butoxide and 3 hr
later each mouse was injected ip with (14)C-dimethylnitrosamine (17
uCi/uM), 2 mg/kg. Mice were sacrificed /4, 8, 12 and 24 hr) after
piperonyl butoxide treatment and the cytochrome
p450 level and macromolecules alkylation were investigated in the
liver. Piperonyl butoxide treatment reduced the
cytochrome p450 level within 4 hr by 34% but induced an incr of
alkylation of macromolecules by (14)C-dimethylnitrosamine: 74% in
cytosolic proteins, 55% in microsomal proteins and 30% in DNA. These
results suggest that p450 dimethylnitrosamine demethylase may not be
the only enzyme involved in dimethylnitrosamine activation. The time
course of this study of this response demonstrates that methylation
of DNA reaches maximal value on the 4 hr and that piperonyl
butoxide had no effect on the DNA repair.
National Toxicology Program Studies:
A bioassay of technical-grade piperonyl butoxide
for possible carcinogenicity was conducted by administering the test
chemical in feed to Fischer 344 rats and B6C3F1 mice. Groups of 50
rats of each sex were administered piperonyl butoxide
in the diet at one of two doses, either 5,000 or 10,000
ppm, for 107 weeks. Matched controls consisted of 20 untreated rats
of each sex. All surviving rats were killed at the end of the period
of administration of the test chemical. Groups of 50 mice of each
sex were initially administered piperonyl butoxide
at one of two doses, either 2,500 or 5,000 ppm. After week 30, the
doses for the mice were reduced to 500 and 2,000 ppm, respectively,
and administration of the test chemical at the lowered doses was
continued for 82 weeks. The time-weighted average doses for the mice
were either 1,036 or 2,804 ppm. Matched controls consisted of 20
untreated mice of each sex. All surviving mice were killed at the
end of the period of administration of the test chemical. It is
concluded that under the conditions of this bioassay,
piperonyl butoxide was not carcinogenic for Fischer 344
rats or B6C3F1 mice. Levels of Carcinogenicity: Male Rats: Negative;
Female Rats: Negative; Male Mice: Negative; Female Mice: Negative.
Non-Human Toxicity Values:
LD50 Rat oral 11.5 g/kg
LD50 Dog oral >7,500 mg/kg
LD50 Cat oral >7,500 mg/kg
LD50 Mouse ip 3,800 mg/kg
LD50 Rat percutaneous >7950 mg/kg
LD50 Rabbit percutaneous 1880 mg/kg
LD50 Mouse oral 2600 mg/kg
LD50 Rabbit oral 2650 mg/kg
Ecotoxicity Values:
LC50 Japanese quail (Coturnix japonica), 14 days old, oral (5 day
ad libitum in diet) > 5,000 ppm /Technical grade, 100% active
ingedient/
LC50 RAINBOW TROUT 3.4 UG/L/96 HR @ 12 DEG C (95% CONFIDENCE
LIMIT 2.7-4.3 UG/L), WT 0.6 G
LC50 BLUEGILL 4.2 UG/L/96 HR @ 18 DEG C (95% CONFIDENCE LIMIT
3.8-4.6 UG/L), WT 0.7 G
Metabolism/Pharmacokinetics:
Metabolism/Metabolites:
IN MICE, THE MAJOR METABOLIC PATHWAY FOR PIPERONYL
BUTOXIDE...INCL CLEAVAGE OF THE METHYLENEDIOXYPHENOL
RESIDUE & EXHALATION OF METHYLENE CARBON ATOM AS CO2. PRODUCTS IN
URINE...COMPRISE MANY COMPOUNDS WITHOUT METHYLENEDIOXYPHENYL RESIDUE
PLUS SMALL AMT OF 6-PROPYLPIPERONYLIC ACID & ITS GLYCINE
CONJUGATE...
In mammals (and also in insects), oxidative attack on the carbon
atom of the methylenedioxy group leads to the formation of the
dihydroxyphenyl compound. Oxidative degradation of the side-chain
also occurs.
Absorption, Distribution & Excretion:
NO...SIGNIFICANT PERCUTANEOUS ABSORPTION /IN TEST MAMMALS/.
DISTRIBUTION OF RADIOACTIVITY SHOWED THAT THE BRAIN & THORACIC
GANGLIA, FORE- & HIND-GUT, & MALPIGHIAN TUBULES OF THE KIDNEY
CONTAINED GREATEST AMT OF.../(14)C-LABELED PIPERONYL
BUTOXIDE/ PER UNIT WT.../IN MADEIRA ROACHES/.
PIPERONYL BUTOXIDE IS POORLY ABSORBED FROM GI
TRACT. IN 2 EXPERIMENTS, 78% & 87%, RESPECTIVELY, OF DOSE ADMIN
ORALLY TO DOGS WERE RECOVERED IN FECES. THE SMALL PROPORTION THAT
WAS ABSORBED FROM GI TRACT WAS RAPIDLY EXCRETED IN URINE.
INTRATRACHEAL ADMIN LED TO MORE PROLONGED EXCRETION OF METABOLITES
IN THE BILE & URINE, BUT EVEN IN THIS INSTANCE RESIDUES IN LUNG
TISSUE WERE LESS THAN THEY WERE FOLLOWING IV ADMIN.
...48 HR AFTER ORAL ADMIN OF...(14)C-PIPERONYL
BUTOXIDE...TO MICE, 76% OF (14)C HAD BEEN EXCRETED IN
EXPIRED AIR, 7% IN URINE, & 4% IN FECES. ...IN RATS, ABOUT 40% WAS
EXCRETED AS (14)C-CO2 IN EXPIRED AIR, 8 HR AFTER IV DOSE...
AFTER IV ADMIN OF LABELED PIPERONYL BUTOXIDE TO
RATS, THE RADIOACTIVITY WAS WIDELY DISTRIBUTED TO VARIOUS TISSUES,
BUT AFTER ORAL ADMIN THE SYNERGIST WAS RATHER POORLY ABSORBED FROM
THE GI TRACT & RAPIDLY EXCRETED IN THE URINE & FECES. INTRATRACHEAL
ADMIN LED TO INITIALLY HIGH LEVELS OF BILIARY EXCRETION FOLLOWED BY
A PROLONGED PERIOD OF ELIMINATION. LOWER LUNG TISSUE RESIDUES OF
UNMETABOLIZED SYNERGIST WERE FOUND AFTER BOTH ORAL & INTRATRACHEAL
ADMIN AS COMPARED TO THAT FOLLOWING IV DOSAGE.
Elimination is as the glucoside or amino acid derivative.
Biological Half-Life:
In order to determine the human in vivo percutaneous absorption
of piperonyl butoxide, a commercial formulation
containing (14C)piperonyl butoxide (3.4 mCi/uM) was
applied to the ventral forearm of six human volunteers. The
formulation contained 3.0% piperonyl butoxide.
Spreadability studies showed that concn 75.8 ug piperonyl
butoxide/sq cm (used in this study) would be consistent
with levels found in actual use. The forearms were thoroughly
cleansed with soap and water 30 min after application (as
recommended for actual use). Percutaneous absorption was determined
by urinary cumulative excretion following dose application. With a 7
day urinary accumulation, ... 2.1+/- 0.6% of the dose of
piperonyl butoxide applied was absorbed through the forearm
skin. 1 hr after application blood samples contained no detectable
radioactivity. The percutaneous absorption ... of piperonyl
butoxide from the scalp was calculated to be 8.3%. ... The
calculated half life of (14)C excretion was 32 hr for
piperonyl butoxide. ...
Mechanism of Action:
INTERACTION OF THESE COMPD WITH CYTOCHROME P-450 RESULTS IN
INHIBITION OF MIXED-FUNCTION OXIDASE ACTIVITY IN MAMMALS.
Interactions:
INHIBITION OF METAB OF DRUGS HAS ALSO BEEN DEMONSTRATED. ...PIPERONYL
BUTOXIDE COMPETITIVELY INHIBITS N-DESETHYLATION OF
ETHYLMORPHINE & O-DEMETHYLATION OF P-NITROANISOLE...
...MOUSE TRIALS INDICATE THAT IT CAN DRAMATICALLY INCR TOXICITY
OF FREONS & GRISEOFULVIN OR VICE VERSA.
IN THE CASE OF CERTAIN SULFUR-CONTAINING ORGANOPHOSPHORUS
INSECTICIDES, WHICH REQUIRE METABOLIC ACTIVATION.../IT IS/
ANTAGONISTIC TO DEVELOPMENT OF NORMAL INSECTICIDAL POTENCY.
PYRETHRIN SYNERGISTS SUCH AS PIPERONYL BUTOXIDE...ARE
EFFECTIVE FOR DDT...FOR CARBAMATES...& FOR DIAZINON, TRICHLORFON, &
OTHER PHOSPHATES...BUT THEY ARE ANTAGONISTIC FOR MALATHION...
PRETREATMENT (24-HR FEEDING) OF DROSOPHILA MELANOGASTER CANTON-S
MALES WITH PIPERONYL BUTOXIDE PRIOR TO EXPOSURE TO
1250 R OF X-RAYS REDUCED YIELD OF 2:3 RECIPROCAL TRANSLOCATIONS &
INCR YIELD OF DOMINANT LETHALS (PROP OF EGGS FAILING TO HATCH).
IN RATS FED 20 OR 40 PPM METHYLMERCURY, ADDITION OF 1%
PIPERONYL BUTOXIDE TO DIET DECREASED MEAN SURVIVAL TIME &
MEAN LATENCY TIME TO NEUROTOXICITY.
PRE-FEEDING OF DROSOPHILA MELANOGASTER WITH PIPERONYL
BUTOXIDE SIGNIFICANTLY INCREASED THE FREQUENCY OF
HELIOTRINE INDUCED CHROMOSOME LOSSES, BUT PRODUCED ONLY A SMALL &
INCONSISTENT REDUCTION IN THE YIELD OF HELIOTRINE INDUCED SEX-LINKED
RECESSIVE LETHALS.
PIPERONYL BUTOXIDE IN VITRO INHIBITS OXIDN &
HYDROLYSIS OF DI-2-ETHYLHEXYL PHTHALATE & HYDROLYSIS OF BUTYL ESTER
OF 2,4-DICHLOROPHENOXYACETIC ACID BY LIVER HOMOGENATE FRACTIONS &
SERUM FROM RAINBOW TROUT (SALMO GAIRDNERI).
Pharmacology:
Therapeutic Uses:
Piperonyl butoxide itself has no known
therapeutic use. ... Formulations of pyrethrins containing
piperonyl butoxide are used as a pediculicide to control
the body louse Pediculus humanus humanus, the head louse, P. humanus
capitus, and the crab louse Pthirus pubis ... .
Interactions:
INHIBITION OF METAB OF DRUGS HAS ALSO BEEN DEMONSTRATED. ...PIPERONYL
BUTOXIDE COMPETITIVELY INHIBITS N-DESETHYLATION OF
ETHYLMORPHINE & O-DEMETHYLATION OF P-NITROANISOLE...
...MOUSE TRIALS INDICATE THAT IT CAN DRAMATICALLY INCR TOXICITY
OF FREONS & GRISEOFULVIN OR VICE VERSA.
IN THE CASE OF CERTAIN SULFUR-CONTAINING ORGANOPHOSPHORUS
INSECTICIDES, WHICH REQUIRE METABOLIC ACTIVATION.../IT IS/
ANTAGONISTIC TO DEVELOPMENT OF NORMAL INSECTICIDAL POTENCY.
PYRETHRIN SYNERGISTS SUCH AS PIPERONYL BUTOXIDE...ARE
EFFECTIVE FOR DDT...FOR CARBAMATES...& FOR DIAZINON, TRICHLORFON, &
OTHER PHOSPHATES...BUT THEY ARE ANTAGONISTIC FOR MALATHION...
PRETREATMENT (24-HR FEEDING) OF DROSOPHILA MELANOGASTER CANTON-S
MALES WITH PIPERONYL BUTOXIDE PRIOR TO EXPOSURE TO
1250 R OF X-RAYS REDUCED YIELD OF 2:3 RECIPROCAL TRANSLOCATIONS &
INCR YIELD OF DOMINANT LETHALS (PROP OF EGGS FAILING TO HATCH).
IN RATS FED 20 OR 40 PPM METHYLMERCURY, ADDITION OF 1%
PIPERONYL BUTOXIDE TO DIET DECREASED MEAN SURVIVAL TIME &
MEAN LATENCY TIME TO NEUROTOXICITY.
PRE-FEEDING OF DROSOPHILA MELANOGASTER WITH PIPERONYL
BUTOXIDE SIGNIFICANTLY INCREASED THE FREQUENCY OF
HELIOTRINE INDUCED CHROMOSOME LOSSES, BUT PRODUCED ONLY A SMALL &
INCONSISTENT REDUCTION IN THE YIELD OF HELIOTRINE INDUCED SEX-LINKED
RECESSIVE LETHALS.
PIPERONYL BUTOXIDE IN VITRO INHIBITS OXIDN &
HYDROLYSIS OF DI-2-ETHYLHEXYL PHTHALATE & HYDROLYSIS OF BUTYL ESTER
OF 2,4-DICHLOROPHENOXYACETIC ACID BY LIVER HOMOGENATE FRACTIONS &
SERUM FROM RAINBOW TROUT (SALMO GAIRDNERI).
Minimum Fatal Dose Level:
2. 2= SLIGHTLY TOXIC: PROBABLE ORAL LETHAL DOSE (HUMAN) 5-15
G/KG, BETWEEN 1 PINT & 1 QUART FOR A 70 KG PERSON (150 LB).
Environmental Fate & Exposure:
Environmental Fate/Exposure Summary:
Piperonyl butoxide's production and use as a
synergist for pyrethrins, rotenone and related insecticides has
resulted in its direct release to the environment. If released to
air, an estimated vapor pressure of 2.6X10-7 mm Hg at 25 deg C
indicates piperonyl butoxide will exist in both the
vapor and the particulate phase in the ambient atmosphere.
Vapor-phase piperonyl butoxide is degraded in the
atmosphere by reaction with photochemically-produced hydroxyl
radicals; the half-life for this reaction in air is estimated to be
4 hours. Particulate-phase piperonyl butoxide may
be removed from the air by wet and dry deposition. If released to
soil, piperonyl butoxide is expected to have
moderate to low mobility based upon Koc values in the range of
399-830. Volatilization from moist soil surfaces is not expected to
be an important fate process based upon an estimated Henry's Law
constant of 8.9X10-11 atm-cu m/mole. Piperonyl butoxide
is not expected to volatilize from dry soil surfaces based
on its estimated vapor pressure. Piperonyl butoxide
is rapidly degraded in soil, with a half-life of 14 days in aerobic
soils. If released into water, piperonyl butoxide
is expected to adsorb to suspended solids and sediment based upon
the Koc. Volatilization from water surfaces is not expected to be an
important fate process based upon this compound's estimated Henry's
Law constant. Piperonyl butoxide is stable to
hydrolysis at pH 5, 7 and 9 under sterile, dark conditions, but was
rapidly degraded (half-life 8.4 hours) in aqueous solution when
illuminated with sunlight. An estimated BCF of 90 suggests the
potential for bioconcentration in aquatic organisms is moderate.
Occupational exposure to piperonyl butoxide may
occur through inhalation and dermal contact with this compound at
workplaces where piperonyl butoxide is produced or
used. The general population may be exposed to piperonyl
butoxide via ingestion of food products containing
piperonyl butoxide. The general population may also be
exposed to piperonyl butoxide through the
application of insecticides containing this compound. (SRC)
Probable Routes of Human Exposure:
Occupational exposure to piperonyl butoxide may
occur through inhalation and dermal contact with this compound at
workplaces where piperonyl butoxide is produced or
used. The general population may be exposed to piperonyl
butoxide via ingestion of food products containing
piperonyl butoxide. The general population may also be
exposed to piperonyl butoxide through the use of
insecticides containing this compound. (SRC)
Artificial Pollution Sources:
Piperonyl butoxide's production and use as a
synergist for pyrethrins, rotenone and related insecticides(1) has
resulted in its direct release to the environment(SRC).
Environmental Fate:
TERRESTRIAL FATE: Based on a classification scheme(1), Koc values
in the range of 399-830(2), indicates that piperonyl
butoxide is expected to have moderate to low mobility in
soil(SRC). Volatilization of piperonyl butoxide
from moist soil surfaces is not expected to be an important fate
process(SRC) given an estimated Henry's Law constant of 4.6X10-9
atm-cu m/mole(SRC), developed using a fragment constant estimation
method(3). Piperonyl butoxide is not expected to
volatilize from dry soil surfaces(SRC) based upon its estimated
vapor pressure of 2.6X10-7 mm Hg(4). Piperonyl butoxide
is rapidly degraded in soil, with a half-life of 14
days(2).
AQUATIC FATE: Based on a classification scheme(1), Koc values in
the range of 399-830(2), indicates that piperonyl butoxide
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 8.9X10-11 atm-cu
m/mole(SRC), developed using a fragment constant estimation
method(4). According to a classification scheme(5), an estimated BCF
of 90(SRC), from a log Kow of 4.75(2) and a regression-derived
equation(6), suggests the potential for bioconcentration in aquatic
organisms is moderate(SRC). The biodegradation half-life of
piperonyl butoxide was reported as 14 days in aerobic
soils(2), suggesting that biodegradation may be important in aerobic
waters(SRC). Piperonyl butoxide is stable to
hydrolysis at pH 5, 7 and 9 under sterile, dark conditions, but was
rapidly degraded (half-life 8.4 hours) in aqueous solution when
illuminated with sunlight(2).
ATMOSPHERIC FATE: According to a model of gas/particle
partitioning of semivolatile organic compounds in the atmosphere(1),
piperonyl butoxide, which has an estimated vapor
pressure of 2.6X10-7 mm Hg at 25 deg C(2) is expected to exist in
both the vapor and the particulate phase in the ambient atmosphere.
Vapor-phase piperonyl butoxide 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 estimated rate constant of
1.07X10-10 cu cm/molecule-sec at 25 deg C(SRC) determined using a
structure estimation method(3). Particulate-phase piperonyl
butoxide may be removed from the air by wet and dry
deposition(SRC).
Environmental Biodegradation:
No information was located concerning the biodegradation of
piperonyl butoxide. However there is data to
indicate that the side chains on the benzodioxole moiety, as well as
the benzodioxole itself biodegrade. It is known that ethoxylate
chains degrade, undergoing rapid stepwise removal of the ethoxy
groups, during wastewater treatment using activated sludge(1-3) and
they also degrade under anaerobic conditions using enriched cultures
from digester sludge(4). Linear side chains on benzene rings also
biodegrade(5-7). Biodegradability has also been shown for two
compounds, piperonal and piperonylic acid, that are related to
piperonyl butoxide (without side chains). Piperonal
readily biodegraded in a screening study using an activated sludge
seed(8) and piperonylic acid is oxidized by soil bacteria(9). These
data suggest that piperonyl butoxide may biodegrade
in the environment(SRC).
AEROBIC: The half-life of piperonyl butoxide in
aerobic soils was reported as 14 days(1). Degradation in soil or
water is mainly via oxidation of the butyl side chain to form
methylenedioxypropyl benzyl alcohol followed by the corresponding
aldehyde, ultimately with mineralization to carbon dioxide; there is
no accumulation of the metabolites(1).
Environmental Abiotic Degradation:
The rate constant for the vapor-phase reaction of
piperonyl butoxide with photochemically-produced hydroxyl
radicals has been estimated as 1.07X10-10 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).
Piperonyl butoxide is stable to hydrolysis at pH 5, 7 and 9
under sterile, dark conditions, but was rapidly degraded (half-life
8.4 hours) in aqueous solution when illuminated with sunlight(2).
After 7 days of exposure to a sunlamp (open dish, weather chamber)
or exposed to sunlight (sealed tube), 95% and 96-98%, respectively
remained undegraded(3). However, piperonyl butoxide
degrades when exposed to sunlight in the presence of a
photosensitizer. When radiolabeled piperonyl butoxide
was combined with 0, 10 and 100 ppm of rotenone, a
photosensitizer with which it is often combined in insecticidal
products, and applied to bean leaves, 12.5. 24.2, and 38.0% of the
radioactivity was recovered in degradation products(4).
Environmental Bioconcentration:
An estimated BCF of 90 was calculated for piperonyl
butoxide(SRC), using a log Kow of 4.75(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.
Soil Adsorption/Mobility:
The Koc of piperonyl butoxide is in the range of
399-830(1). According to a classification scheme(2), these Koc
values suggest that piperonyl butoxide is expected
to have moderate to low mobility in soil.
Volatilization from Water/Soil:
The Henry's Law constant for piperonyl butoxide
is estimated as 8.9X10-11 atm-cu m/mole(SRC) using a fragment
constant estimation method(1). This Henry's Law constant indicates
that piperonyl butoxide is expected to be
essentially nonvolatile from water surfaces(2). Piperonyl
butoxide's estimated Henry's Law constant(1) indicates that
volatilization from moist soil surfaces is not expected(SRC).
Piperonyl butoxide is not expected to volatilize
from dry soil surfaces(SRC) based upon its estimated vapor pressure
of 2.6X10-7 mm Hg at 25 deg C(3).
Environmental Water Concentrations:
Piperonyl butoxide was detected in 1 out of 83
samples of surface water from Spain at a concn of 1.6 ug/l(1).
Effluent Concentrations:
Piperonyl butoxide was not detected in runoff
water following application of a multi-purpose insecticide
containing this compound(1).
Sediment/Soil Concentrations:
Piperonyl butoxide was detected at concns of
0.03-0.84 ug/g in soil following application of a multi-purpose
insecticide containing this compound to farmland in KY(1).
Food Survey Values:
In a study in which 531 samples of grain and beans from the U.S.,
Japan, Australia, Korea, Canada and other countries were analyzed
for piperonyl butoxide, only 6 of 201 samples of
grain, 3 wheat from the U.S. and 3 barley from the U.S. and
Australia, contained residues up to 1.4 ppm(1). None of the 226
samples of hulled and unhulled rice or 52 samples of soy and red
beans contained piperonyl butoxide. Piperonyl butoxide
was identified, not quantified, in domestic and imported
pears(2). Piperonyl butoxide was detected in 46 out
of 769 domestic apples at a max concn of 1.6 ppm and in 52 out of
1,062 imported apples at a max concn of 0.47 ppm(3).
Environmental Standards & Regulations:
FIFRA Requirements:
As the federal pesticide law FIFRA directs, EPA is conducting a
comprehensive review of older pesticides to consider their health
and environmental effects and make decisions about their future use.
Under this pesticide reregistration program, EPA examines health and
safety data for pesticide active ingredients initially registered
before November 1, 1984, and determines whether they are eligible
for reregistration. In addition, all pesticides must meet the new
safety standard of the Food Quality Protection Act of 1996.
Pesticides for which EPA had not issued Registration Standards prior
to the effective date of FIFRA, as amended in 1988, were divided
into three lists based upon their potential for human exposure and
other factors, with List B containing pesticides of greater concern
and List D pesticides of less concern. Piperonyl butoxide
is found on List B. Case No: 2525; Pesticide type:
Insecticide, fungicide, rodenticide, antimicrobial; 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): Butylcarbitol (6-propylpiperonyl) ether 80% and
related compounds; Data Call-in (DCI) Date(s): 05/13/91, 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 for residues of the insecticide piperonyl
butoxide [(butyl carbityl)(6-propyl piperonyl)ether] are
established in or on the following food commodities: almonds
(post-H); apples (post-H); barley (post-H); beans (post-H); birdseed
mixtures (post-H); blackberries (post-H); blueberries
(huckleberries) (post-H); boysenberries (post-H); buckwheat
(post-H); cattle (fat, mbyp, and meat); cherries (post-H); cocoa
beans (post-H); copra (post-H); corn (including popcorn) (post-H);
cottonseed (post-H); crabapples (post-H); currants (post-H);
dewberries (post-H); eggs, 1 ppm; figs (post-H); flaxseed (post-H);
goats (fat, mbyp, and meat); gooseberries (post-H); grain sorghum
(post-H); grapes (post-H); guavas (post-H); hogs (fat, mbyp, and
meat); horses (fat, mbyp, and meat); loganberries (post-H); mangoes
(post-H); milk fat (reflecting negligible residues in milk);
muskmelons (post-H); oats (post-H); oranges (post-H); peaches
(post-H); peanuts (with shell removed) (post-H); pears (post-H);
peas (post-H); pineapples (post-H); plums (fresh prunes) (post-H);
potatoes (post-H); poultry (fat, mbyp, and meat), 3 ppm; raspberries
(post-H); rice (post-H); rye (post-H); sheep (fat, mbyp, and meat);
sweet potatoes (post-H); tomatoes (post-H); walnuts (post-H); wheat
(post-H).
When applied to growing crops, in accordance with good
agricultural practice, the following pesticide chemicals are exempt
from the requirement of a tolerance: piperonyl butoxide.
These pesticides are not exempted from the requirement of a
tolerance when applied to a crop at the time of or after harvest.
When applied to growing crops, in accordance with good
agricultural practice, the following pesticide chemicals are exempt
from the requirement of a tolerance: piperonyl butoxide.
These pesticides are not exempted from the requirement of a
tolerance when applied to a crop at the time of or after harvest.
Chemical/Physical Properties:
Molecular Formula:
C19-H30-O5
Molecular Weight:
338.43
Color/Form:
Colorless liquid
PALE YELLISH LIQ
Odor:
ODORLESS
Odor: mild.
Taste:
FAINT BITTER TASTE
Boiling Point:
180 deg C @ 1 mm Hg
Corrosivity:
NONCORROSIVE
Density/Specific Gravity:
1.06 @ 20 deg C
Octanol/Water Partition Coefficient:
log Kow= 4.75
Solubilities:
Miscible with methanol, ethanol, benzene, freons, geons,
petroleum oils, and other organic solvents
Tests on eyes and skin of rabbits, rats, cats, and dogs showed
that it was not damaging, although it may be irritating.
Fire Potential:
COMBUSTIBLE WHEN EXPOSED TO HEAT OR FLAME; CAN REACT WITH
OXIDIZING MATERIALS.
Flash Point:
340 DEG F
Fire Fighting Procedures:
TO FIGHT FIRE, USE FOAM, CARBON DIOXIDE, DRY CHEMICAL.
Hazardous Reactivities & Incompatibilities:
... CAN REACT WITH OXIDIZING MATERIALS.
Hazardous Decomposition:
When heated to decomp it emits acrid smoke and irritating fumes.
Stability/Shelf Life:
Very stable to hydrolysis and uv irradiation.
STABLE AT 100 DEG C; THIN FILMS OF COMMERCIAL GRADE MATERIAL ARE
STABLE TO INTENSE FLUORESCENT LIGHT FOR UP TO 7 DAYS
Storage Conditions:
IN GENERAL MATERIALS...TOXIC AS STORED OR WHICH CAN DECOMP INTO
TOXIC COMPONENTS...SHOULD BE STORED IN COOL...VENTILATED PLACE, OUT
OF...SUN, AWAY FROM...FIRE HAZARD.../& SHOULD BE/ PERIODICALLY
INSPECTED & MONITORED. INCOMPATIBLE MATERIALS SHOULD BE ISOLATED.
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.
Occupational Exposure Standards:
Manufacturing/Use Information:
Major Uses:
For Piperonyl butoxide (USEPA/OPP Pesticide
Code: 067501) 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 synergist, esp for pyrethrum and rotenone
Synergist for the pyrethrins and related insecticides
MEDICATION
Anvil is a pesticide product that is used to control mosquitoes
in outdoor residential and recreational areas. It contains
sumithrin, piperonyl butoxide and petroleum
solvents. ... Piperonyl butoxide does not directly
kill insects on its own but acts to increase the ability of
sumithrin to kill insects. Other pesticide products containing these
ingredients are used indoors and on pets to control insects such as
fleas, ticks, and ants.
Manufacturers:
McLaughlin Gormley King Co., Hq, 8810 Tenth Ave. North,
Minneapolis, MN 55427, (763) 544-0341; Production site: Chaska, MN
55318
Archimica, Inc., 2114 Larry Jeffers Rd, Elgin, SC 29045; (803)
438-3471; Production site: Elgin, SC 29045
Findett Corp., 8 Governor Dr., St. Charles, MO 63301-7311, (636)
723-0240; Production site: St. Charles, MO 63301-7311
Methods of Manufacturing:
REACTION OF THE CHLOROMETHYL DERIVATIVE OF DIHYDROSAFROLE WITH
THE SODIUM SALT OF BUTYL CARBITOL
...BY CONDENSING 5-CHLOROMETHYL-6-PROPYL-1,3-BENZODIOXOLE WITH
SODIUM-2(2-BUTOXYETHOXY)ETHOXIDE...
Wachs, US patents, 2,485,681; 2,550,737 (1949, 1951, both to US
Industrial Chemicals); Science 105, 530 (1947).