PIPERONYL BUTOXIDE
Human Health Effects:
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.
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. ...
Probable Routes of Human Exposure:
Exposure to piperonyl butoxide would occur by inhalation of aerosols or by dermal
contact during application(SRC). Dermal contact with piperonyl butoxide also will occur by
touching treated plants, soil, and surfaces before the chemical is dissipated. (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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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, *** 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: |
SUMMARY OF EXPOSURE
0.2.1.1 ACUTE EXPOSURE
o 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.
o The MINIMAL TOXIC OR LETHAL DOSE is not established.
o PHARMACOLOGIC EFFECT - Piperonyl butoxide inhibits
mixed function oxidase enzymes of the liver which
metabolize pyrethrins and pyrethroids, with which they
are combined.
HEENT
0.2.4.1 ACUTE EXPOSURE
o Piperonyl butoxide may cause eye irritation, but is not
damaging.
NEUROLOGIC
0.2.7.1 ACUTE EXPOSURE
o 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.
GASTROINTESTINAL
0.2.8.1 ACUTE EXPOSURE
o Nausea, vomiting, anorexia, or diarrhea may be seen.
HEPATIC
0.2.9.1 ACUTE EXPOSURE
o Hepatic changes and liver injury have been seen with
large doses given to various animal species.
HEMATOLOGIC
0.2.13.1 ACUTE EXPOSURE
o Various anemias have been reported in animal studies.
DERMATOLOGIC
0.2.14.1 ACUTE EXPOSURE
o Skin irritation or significant percutaneous absorption
is not expected following normal dermal exposure.
METABOLISM
0.2.17.1 ACUTE EXPOSURE
o Animal studies have shown elevated metabolic enzymes
after ingestion of this compound.
REPRODUCTIVE HAZARDS
o Mixed results for teratogenicity have been obtained in
animals.
CARCINOGENICITY
0.2.21.2 HUMAN OVERVIEW
o Piperonyl butoxide induced hepatocellular carcinomas in
mice and rats in dietary studies (Takahashi et al,
1994a, 1994b).
GENOTOXICITY
o At the time of this review, no data were available to
assess the mutagenic or genotoxic potential of this
agent.
|
| Laboratory: |
o PIPERONYL BUTOXIDE LEVELS are not clinically useful.
o No specific lab work is needed unless otherwise indicated
by the patient's condition.
|
| Treatment Overview: |
SUMMARY EXPOSURE
o GENERAL -
Little if any treatment is required for exposure to
amounts normally found in products. Treatment may be
required for the hydrocarbons or other insecticides with
which it is combined. Other treatment is symptomatic
and supportive. Severe toxicity is not expected.
o EMESIS-
Is not indicated at home if hydrocarbons are present.
ORAL EXPOSURE
o Piperonyl butoxide is of low toxicity. Gastric
decontamination is only indicated if there is a
coingestant with significant toxicity.
o 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.
o ACTIVATED CHARCOAL: Administer charcoal as 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.
o NATIONAL PESTICIDE HOTLINE -
1. Provides consultation to poison centers and other
health professionals for the management of pesticide
poisoning. Calls regarding emergency cases requiring
immediate medical response will be transferred to the
Oregon Poison Center. The National Pesticide
Telecommunications Network has a toll-free number,
1-800-858-7378, or if outside the U.S., the
non-toll-free number is 541-737-6094. Hours are 6:30
AM to 4:30 PM Pacific time 7 days/week excluding
holidays. FAX: 1-541-737-0761. email:
nptn@ace.orst.edu
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.
|
| Range of Toxicity: |
o 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.
o Male volunteers tolerated a single oral dose of 50 mg
(0.71 mg/kg body weight) piperonyl butoxide with no signs
of toxicity.
|
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.
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).
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).
Tests on eyes and skin of rabbits, rats, cats, and dogs showed that it was not
damaging, although it may be irritating.
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
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 ASELLUS 12 UG/L/96 HR @ 15 DEG C (95% CONFIDENCE LIMIT 7-22 UG/L), MATURE
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...
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.
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.
...ADMIN (14)C-CHLOROFORM TO MALE MICE & MONITORED RENAL NECROSIS & CONVALENT
BINDING OF (14)C TO RENAL PROTEIN. CHLOROFORM PRODUCED NECROSIS...IN PROXIMAL TUBULES.
TREATMENT OF MICE WITH PIPERONYL BUTOXIDE...REDUCED EXTENT OF RENAL NECROSIS & BINDING
OF (14)C TO RENAL PROTEINS IN VIVO.
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.
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.
...ADMIN (14)C-CHLOROFORM TO MALE MICE & MONITORED RENAL NECROSIS & CONVALENT
BINDING OF (14)C TO RENAL PROTEIN. CHLOROFORM PRODUCED NECROSIS...IN PROXIMAL TUBULES.
TREATMENT OF MICE WITH PIPERONYL BUTOXIDE...REDUCED EXTENT OF RENAL NECROSIS & BINDING
OF (14)C TO RENAL PROTEINS IN VIVO.
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.
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 will be released to the environment during its use as a synergist
for pyrethrins, rotenone and related insecticides for household and agricultural use. It
may also be released to the environment during its production, transport, formulation,
storage, and disposal. If released on soil, piperonyl butoxide would be expected to leach.
No information was found concerning its biodegradation; however based on data on related
chemicals, piperonyl butoxide may biodegrade. If released in water, piperonyl butoxide is
not expected to volatilize or adsorb to sediment. In the presence of photosensitizers, it
may photodegrade in surface waters. Otherwise, its degradation in the aquatic environment
is unknown. Piperonyl butoxide is estimated to be moderately bioconcentrating in aquatic
organisms. If piperonyl butoxide is released into the atmosphere as an aerosol during
spraying, it will be removed by gravitational settling. Vapor-phase piperonyl butoxide
will react with photochemically-produced hydroxyl radicals resulting in an estimated
atmospheric half-life of 3.4 hr. Exposure to piperonyl butoxide would be via inhalation
and dermal contact with the spray or dermal contact with treated surfaces. (SRC)
Probable Routes of Human Exposure:
Exposure to piperonyl butoxide would occur by inhalation of aerosols or by dermal
contact during application(SRC). Dermal contact with piperonyl butoxide also will occur by
touching treated plants, soil, and surfaces before the chemical is dissipated. (SRC)
Artificial Pollution Sources:
Piperonyl butoxide will be released to the environment during its use as a synergist
for pyrethrins, rotenone and related insecticides for household and agricultural use(1,4).
It is the synergist most commonly used with natural pyrethrins in pressurized aerosol
sprays(3). Products containing piperonyl butoxide are available as dusts, emulsifiable
concentrates, foggers, paper coatings, pressurized sprays, solutions, and wettable
powders(2) and the formulation used will affect its environmental release. Piperonyl
butoxide may also be released to the environment during its production, transport,
formulation, storage, and disposal.
Environmental Fate:
TERRESTRIAL FATE: If released on soil, piperonyl butoxide would be expected to leach
based on an estimated Koc of 70(1). No information was found concerning biodegradation of
piperonyl butoxide or half-lives in soil or other environmental media. However piperonyl
butoxide's biodegradability is suggested by data on related chemicals(SRC).
AQUATIC FATE: If released in water, piperonyl butoxide is not expected to volatilize or
adsorb to sediment. In the presence of photosensitizers, such as rotenone, it may
photodegrade in surface waters. Otherwise, its degradation in the aquatic environment is
unknown. (SRC)
ATMOSPHERIC FATE: If piperonyl butoxide is released into the atmosphere as an aerosol
during spraying, it will be removed by gravitational settling. Vapor-phase piperonyl
butoxide will react with photochemically-produced hydroxyl radicals resulting in an
estimated atmospheric half-life of 3.4 hr(1).
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(1,2,3) and they also degrade under anaerobic conditions using enriched cultures
from digester sludge(4). Linear side chains on benzene rings also biodegrade(5,6,7).
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).
Environmental Abiotic Degradation:
Piperonyl butoxide is stable to light and resistant to hydrolysis (1). 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(2). In the atmosphere,
piperonyl butoxide will exist partially as an aerosol and partially as the vapor(5).
Vapor-phase piperonyl butoxide will react with photochemically-produced hydroxyl radicals
with an estimated rate constant of 1.11X10-10 cu cm/molecule-s(4). Assuming a hydroxyl
radical concn of 5X10+5 radicals/cu cm, the half-life of piperonyl butoxide in the
atmosphere would be 3.4 hr(SRC).
Environmental Bioconcentration:
Using the estimated log Kow of 4.29(1) for piperonyl butoxide, one would estimate a BCF
of 1100 using a recommended regression equation(2). This would indicate that piperonyl
butoxide would bioconcentrate in aquatic organisms(SRC).
Soil Adsorption/Mobility:
The Koc for piperonyl butoxide estimated from molecular structure is 70(1). According
to a suggested classification scheme(2), chemicals with Koc values of this magnitude will
have high mobility in soil(SRC).
Volatilization from Water/Soil:
The Henry's Law constant for piperonyl butoxide estimated from structure activity
relationships is 2.45X10-9 atm-cu-m/mol(1). Chemicals with such low Henry's Law constants
will be nonvolatile from water(2). In view of its low estimated vapor pressure, 2.6X10-7
mm Hg at 25 degC(3), little volatilization from soil would be expected(SRC).
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 residues.
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 are established in or on
the following raw agricultural commodities: almonds; apples; barley; beans; birdseed
mixtures; blackberries; blueberries (huckleberries); boysenberries; buckwheat; cattle
(fat, mbyp, and meat); cherries; cocoa beans; copra; corn (including popcorn); cottonseed;
crabapples; currants; dewberries; eggs; figs; flaxseed; goats (fat, mbyp, and meat);
gooseberries; grain sorghum; guavas; hogs (fat, mbyp, and meat); horses (fat, mbyp, and
meat); loganberries; mangoes; milk fat (reflecting negligible residues in milk);
muskmelons; oats; oranges; peaches; peanuts (with shell removed); pears; peas; pineapples;
plums (fresh prunes); potatoes; poultry (fat, mbyp, and meat); raspberries; rice; rye;
sheep (fat, mbyp, and meat); sweet potatoes; tomatoes; walnuts (post-H); and wheat.
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.
In cereal grain mills and in storage areas for milled cereal grain products, whereby
the amount of piperonyl butoxide is at least equal to but not more than 10 times the
amount of pyrethrins in the formulation.
On the outer ply of multiwall paper bags of 50 pounds or more capacity in amounts not
exceeding 60 milligrams per square foot, whereby the amount of piperonyl butoxide is equal
to 10 times the amount of pyrethrins in the formulation. Such treated bags are to be used
only for dried foods.
On cotton bags of 50 pounds or more capacity in amounts not exceeding 55 milligrams per
square foot of cloth, whereby the amount of piperonyl butoxide is equal to 10 times the
amount of pyrethrins in the formulation. Such treated bags are constructed with wax paper
liners and are to be used only for dried foods that contain 4% fat or less.
In two-ply bags consisting of cellophane/ polyolefin sheets bound together by an
adhesive layer when it is incorporated in the adhesive. The treated sheets shall contain
more than 50 milligrams of piperonyl butoxide per square foot (538 milligrams per square
meter). Such treated bags are to be used only for packaging prunes, raisins, and other
dried fruits and are to have a maximum ratio of 3.12 milligrams of piperonyl butoxide per
ounce of fruit (0.10 milligram of piperonyl butoxide per gram of product).
It is used or intended for use in combination with pyrethrins and N-octylbicycloheptene
dicarboximide for insect control in accordance with 40 CFR 178.3730.
Milled fractions derived from cereal grains when present therein as a result of its use
in cereal grain mills and in storage areas for milled cereal grain products.
Dried foods when present as a result of migration from its use on the outer ply of
multiwall paper bags of 50 pounds or more capacity.
Dried foods that contain 4% fat, or less, when present as a result of migration from
its use on the cloth of cotton bags of 50 pounds or more capacity constructed with waxed
papaer liners.
To assure safe use of the additive, its label and labeling shall conform to that
registered with the U.S. EPA and it shall be used in accordance with such label and
labeling.
Where tolerances are established under sections 408 and 409 of the Act on both raw
agricultural commodities and processed foods made therefrom, the total residues of
piperonyl butoxide in or on the processed food shall not be greater than that permitted by
the larger of the two tolerances.
It is used or intended for use in combination with pyrethrins for control of insects:
On the outer ply of multiwall paper bags of 50 pounds or more capacity in amounts not
exceeding 60 milligrams per square foot.
On cotton bags of 50 pounds or more capacity in amounts not exceeding 55 milligrams per
square foot of cloth. Such treated bags are constructed with waxed paper liners and are to
be used only for dried feeds that contain 4% fat or less.
It is used in combination with pyrethrins, whereby the amount of piperonyl butoxide is
equal to 10 times the amount of pyrethrins in the formulation. Such treated bags are to be
used only for dried feeds.
In or on dried feeds from its use on the outer ply of multiwall paper bags of 50 pounds
or more capacity.
In or on dried feeds that contain 4% fat, or less, from its use on cotton bags of 50
pounds or more capacity constructed with waxed paper liners.
To assure safe use of the additive, its label and labeling shall conform to that
registered with the U.S. EPA.
Where tolerances are established under sections 408 and 409 of the Act on both raw
agricultural commodities and processed foods made therefrom, the total residues of
piperonyl butoxide in or on the processed food shall not be greater than that permitted by
the larger of the two tolerances.
Acceptable Daily Intakes:
FAO/WHO ADI: 0.03 mg/kg
Allowable Tolerances:
Tolerances for residues of the insecticide piperonyl butoxide are established in or on
the following raw agricultural commodities: almonds (post-H), 8 ppm; apples (post-H), 8
ppm; barley (post-H), 20 ppm; beans (post-H), 8 ppm; birdseed mixtures (post-H, 20 ppm);
blackberries (post-H), 8 ppm; blueberries (huckleberries) (post-H), 8 ppm; boysenberries
(post-H), 8 ppm; buckwheat (post-H), 20 ppm; cattle (fat, mbyp, and meat), 0.1 (N) ppm;
cherries (post-H), 8 ppm; cocoa beans (post-H), 8 ppm; copra (post-H), 8 ppm; corn
(including popcorn) (post-H), 20 ppm; cottonseed (post-H), 8 ppm; crabapples (post-H), 8
ppm; currants (post-H), 8 ppm; dewberries (post-H), 8 ppm; eggs, 1 ppm; figs (post-H), 8
ppm; flaxseed (post-H), 8 ppm; goats (fat, mbyp, and meat), 0.1 (N) ppm; gooseberries
(post-H), 8 ppm; grain sorghum (post-H), 8 ppm; guavas (post-H), 8 ppm; hogs (fat, mbyp,
and meat), 0.1 (N) ppm; horses (fat, mbyp, and meat), 0.1 (N) ppm; loganberries (post-H),
8 ppm; mangoes (post-H), 8 ppm; milk fat (reflecting negligible residues in milk), 0.25
ppm; muskmelons (post-H), 8 ppm; oats (post-H), 8 ppm; oranges (post-H), 8 ppm; peaches
(post-H), 8 ppm; peanuts (with shell removed) (post-H), 8 ppm; pears (post-H), 8 ppm; peas
(post-H), 8 ppm; pineapples (post-H), 8 ppm; plums (fresh prunes) (post-H), 8 ppm;
potatoes (post-H), 8 ppm; poultry (fat, mbyp, and meat), 3 ppm; raspberries (post-H), 8
ppm; rice (post-H), 20 ppm; rye (post-H), 20 ppm; sheep (fat, mbyp, and meat), 0.1 (N)
ppm; sweet potatoes (post-H), 0.25 ppm; tomatoes (post-H), 8 ppm; walnuts (post-H), 8 ppm;
wheat (post-H), 20 ppm.
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.
The food additive piperonyl butoxide may be safely used in accordance with the
following prescribed conditions:
It is used or intended for use in combination with pyrethrins for control of insects:
In cereal grain mills and in storage areas for milled cereal grain products, whereby
the amount of piperonyl butoxide is at least equal to but not more than 10 times the
amount of pyrethrins in the formulation.
On the outer ply of multiwall paper bags of 50 pounds or more capacity in amounts not
exceeding 60 milligrams per square foot, whereby the amount of piperonyl butoxide is equal
to 10 times the amount of pyrethrins in the formulation. Such treated bags are to be used
only for dried foods.
On cotton bags of 50 pounds or more capacity in amounts not exceeding 55 milligrams per
square foot of cloth, whereby the amount of piperonyl butoxide is equal to 10 times the
amount of pyrethrins in the formulation. Such treated bags are constructed with wax paper
liners and are to be used only for dried foods that contain 4% fat or less.
In two-ply bags consisting of cellophane/ polyolefin sheets bound together by an
adhesive layer when it is incorporated in the adhesive. The treated sheets shall contain
more than 50 milligrams of piperonyl butoxide per square foot (538 milligrams per square
meter). Such treated bags are to be used only for packaging prunes, raisins, and other
dried fruits and are to have a maximum ratio of 3.12 milligrams of piperonyl butoxide per
ounce of fruit (0.10 milligram of piperonyl butoxide per gram of product).
In food processing and food storage areas: Provided, that the food is removed or
covered prior to such use.
It is used or intended for use in combination with pyrethrins and N-octylbicycloheptene
dicarboximide for insect control in accordance with 40 CFR 178.3730.
Milled fractions derived from cereal grains when present therein as a result of its use
in cereal grain mills and in storage areas for milled cereal grain products.
Dried foods when present as a result of migration from its use on the outer ply of
multiwall paper bags of 50 pounds or more capacity.
Foods treated in accordance with 40 CFR 178.3730.
Dried foods that contain 4% fat, or less, when present as a result of migration from
its use on the cloth of cotton bags of 50 pounds or more capacity constructed with waxed
papaer liners.
To assure safe use of the additive, its label and labeling shall conform to that
registered with the U.S. EPA and it shall be used in accordance with such label and
labeling.
Where tolerances are established under sections 408 and 409 of the Act on both raw
agricultural commodities and processed foods made therefrom, the total residues of
piperonyl butoxide in or on the processed food shall not be greater than that permitted by
the larger of the two tolerances.
It is used or intended for use in combination with pyrethrins for control of insects:
On the outer ply of multiwall paper bags of 50 pounds or more capacity in amounts not
exceeding 60 milligrams per square foot.
On cotton bags of 50 pounds or more capacity in amounts not exceeding 55 milligrams per
square foot of cloth. Such treated bags are constructed with waxed paper liners and are to
be used only for dried feeds that contain 4% fat or less.
It is used in combination with pyrethrins, whereby the amount of piperonyl butoxide is
equal to 10 times the amount of pyrethrins in the formulation. Such treated bags are to be
used only for dried feeds.
A tolerance of 10 ppm is established for residues of piperonyl butoxide when present as
the result of migration:
In or on dried feeds from its use on the outer ply of multiwall paper bags of 50 pounds
or more capacity.
In or on dried feeds that contain 4% fat, or less, from its use on cotton bags of 50
pounds or more capacity constructed with waxed paper liners.
To assure safe use of the additive, its label and labeling shall conform to that
registered with the U.S. EPA.
Chemical/Physical Properties:
Molecular Formula:
C19-H30-O5
Molecular Weight:
338.43
Color/Form:
LIGHT BROWN LIQ
PALE YELLISH LIQ
Odor:
ODORLESS
Odor: mild.
Taste:
FAINT BITTER TASTE
Boiling Point:
180 DEG C @ 1 MM HG
Density/Specific Gravity:
1.05-1.07 @ 25 DEG C
Solubilities:
MISCIBLE WITH METHANOL, ETHANOL, BENZENE, FREONS, GEONS, PETROLEUM OILS, & OTHER
ORGANIC SOLVENTS
Very slightly soluble in water.
Spectral Properties:
Intense mass spectral peaks: 176 m/z (100%), 177 m/z (41%), 194 m/z (26%), 57 m/z (19%)
INDEX OF REFRACTION: 1.497-1.512 @ 20 DEG C/D
Other Chemical/Physical Properties:
RESISTANT TO HYDROLYSIS & NONCORROSIVE
Stable to light, resistant to hydrolysis.
Chemical Safety & Handling:
Fire Potential:
SLIGHT, WHEN EXPOSED TO HEAT OR FLAME; CAN REACT WITH OXIDIZING MATERIALS
Flash Point:
340 DEG F
Fire Fighting Procedures:
FOAM, CARBON DIOXIDE, DRY CHEM
Stability/Shelf Life:
STABLE TO LIGHT
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:
INSECTICIDE SYNERGIST, ESP FOR PYRETHRUM & ROTENONE
SYNERGIST FOR THE PYRETHRINS & 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, (612)
544-0341
Hardwicke Chemical, Inc., 2114 Larry Jeffers Rd, Elgin, SC 29045; (803) 438-3471.
International Chemical Group, Hqr, 1801 Diamond St, Suite 3-118, Pacific Beach, CA
92109, (619) 274-7215; Manufacturing site: Int Marketing Ctr, 4740 La Rueda Dr, La Mesa,
CA 91941, (619) 441-9108.
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...
General Manufacturing Information:
WACHS, US PATENTS, 2,485,681; 2,550,737 (1949, 1951, BOTH TO US INDUSTRIAL CHEMICALS);
SCIENCE 105, 530 (1947).
Formulations/Preparations:
MIXT OF PYRETHRIN & PIPERONYL BUTOXIDE REGISTERED AS PYRENONES BY FAIRFIELD AMERICA
CORP IN USA, AS PYBUTHRINS BY COOPER, MCDOUGALL & ROBERTSON LTD IN GREAT BRITAIN,
& PYROCIDES BY MCLAUGHLIN GORMLEY KING CO IN USA.
Available in various mixtures with synthetic pyrethroids, eg, Derringer, Duracide,
Grovex, Prentox, Scourge; also in combination with rotenone, qv, PB-NOX, Chem-fish,
Rotacide.
Dust, emulsifiable concentrate, fogger, paper coating, pressurized spray, solution,
wettable powder.
INGREDIENT OF INSECTICIDAL OIL SOLN, AEROSOLS, DUSTS, WETTABLE POWDERS, SLURRIES
Anvil is a pesticide product that is used to control mosquitoes ... contains sumithrin,
piperonyl butoxide and petroleum solvents.
Consumption Patterns:
SYNERGIST WITH INSECTICIDES, OF WHICH 80% IS USED IN HOUSEHOLD, COMMERCIAL, &
INDUSTRIAL APPLICATIONS AND 20% IN AGRICULTURE FOR LIVESTOCK & POULTRY (1975)
U. S. Production:
(1975) 4.54X10+8 GRAMS (CONSUMPTION)
(1976) PROBABLY GREATER THAN 2.27X10+6 GRAMS
Laboratory Methods:
Analytic Laboratory Methods:
(A) BY REACTION WITH GALLIC ACID IN PRESENCE OF SULFURIC ACID, BLUE COMPLEX MEASURED AT
660 MU...BLUM, MS, J AGR FOOD CHEM, 3, 122, 1955. (B) BY REACTION WITH...TANNIC ACID IN
MIXTURE OF PHOSPHORIC & ACETIC ACIDS TO GIVE BLUE COLOR, DETERMINE AT 625-635
MU...(JONES, HA ET AL, J ASSOC OFF AGR CHEM, 35, 771, 1952). (C) LIBERATION OF
FORMALDEHYDE FROM METHYLENEDIOXYL OR COMBINED FORMALDEHYDE GROUPS BY STRONG SULFURIC ACID
& DETERMINATION OF FORMALDEHYDE WITH CHROMOTROPIC SULFURIC ACID. BEROZA CLAIMED
SENSITIVITY TO 1 UG, (J AGR CHEM, 4, 55, 1956).../&/ (E) ANAL METHODS FOR PESTICIDES
& PLANT GROWTH REGULATORS, EDITORS, ZWEIG, G & SHERMA J, ACADEMIC PRESS, VI, 458,
1972. PRODUCT ANALYSIS: DETERMINATION IN PESTICIDES BY COLORIMETRY.
DETERMINATION IN PESTICIDES BY COLORIMETRY.
SEVERAL PROCEDURES FOR EXAMINING SPECIMENS ARE PRESENTED SUCH AS THIN LAYER
CHROMATOGRAPHY, NUCLEAR MAGNETIC RESONANCE & SPECTROSCOPY.
APPLICABLE TO ALASKA PEAS, BARLEY, HULLED RICE, OATS, & PINTO BEANS. ...MEASURE
ABSORPTION IN SPECTROPHOTOMETER AT 575 NM...
GENERAL SAMPLE; SPECTROPHOTOMETRY @ 625-635 NM: ZWEIG, GUNTER, ANALYTICAL METHODS FOR
PESTICIDES, PLANT GROWTH REGULATORS, & FOOD ADDITIVES, ACADEMIC PRESS, NY, NY, VOL 2:
396 (1964).
GAS-LIQ CHROMATOGRAPHY: BARRETTE, JP & R PAYFER, J ASSOC OFFIC AGR CHEM 47, 262
(1964). GUDZINOWICZ, BJ, "THE ANALYSIS OF PESTICIDES, HERBICIDES & RELATED COMPD
USING ELECTRON AFFINITY DETECTOR," JARELL-ASH CO, WALTHAM, MASS (JUNE 1965).
THIN-LAYER CHROMATOGRAPHY: BEROZA, MOLTEN, AGR FOOD CHEM 11, 52 (1963).
HIGH SPEED LIQ CHROMATOGRAPH EQUIPPED WITH FLUOROMETRIC DETECTOR WAS USED TO DETERMINE
RESIDUAL LEVELS OF PIPERONYL BUTOXIDE IN RICE, WHEAT, BARLEY, RYE & OTHER AGRICULTURAL
PRODUCTS. DETECTION LIMIT WAS 0.1 PPM.
VARIETY OF CHROMATOGRAPHIC PROCEDURES ARE DESCRIBED SUCH AS GLC, TLC, GLC/MS WITH
PARTICULAR FOCUS PLACED ON CHROMATOGRAPHIC ASPECTS OF PIPERONYL BUTOXIDE.
PIPERONYL BUTOXIDE WAS DETERMINED IN CROPS BY HIGH SPEED LIQ CHROMATOGRAPHY USING
EITHER FLUORESCENCE DETECTOR OR ULTRAVIOLET DETECTOR. DETECTION LIMITS WERE 10 & 1
MUG/ML RESPECTIVELY WITH THESE TWO DETECTORS.
Special References:
Special Reports:
-4,5-METHYLENEDIOXY-2-PROPYLTOLUENE: A REVIEW OF THE LITERATURE; ECOTOXICOL ENVIRON
SAFETY 2(1) 31 (1978)] A LITERATURE REVIEW ON PIPERONYL BUTOXIDE COVERING CHEMISTRY,
ADVERSE EFFECTS, BIOTRANSFORMATION, CARCINOGENICITY, & PESTICIDE SYNERGISTS.
Bioassay of Piperonyl Butoxide for Possible Carcinogenicity (1979) Technical Rpt Series
No. 120 DHEW Pub No. (NIH) 79-1375, U.S. Department of Health Education and Welfare,
National Cancer Institute, Bethesda, MD 20014
Synonyms and Identifiers:
Synonyms:
1,3-BENZODIOXOLE, 5-((2-(2-BUTOXYETHOXY)ETHOXY)METHYL)-6-PROPYL-
**PEER REVIEWED**
BUTACIDE
**PEER REVIEWED**
BUTOCIDE
**PEER REVIEWED**
BUTOXIDE
**PEER REVIEWED**
ALPHA-(2-(2-N-BUTOXYETHOXY)-ETHOXY)-4,5-METHYLENEDIOXY-2-PROPYLTOLUENE
**PEER REVIEWED**
5-((2-(2-BUTOXYETHOXY)ETHOXY)METHYL-6-PROPYL-1,3-BENZODIOXOLE
**PEER REVIEWED**
BUTYL CARBITOL 6-PROPYLPIPERONYL ETHER
**PEER REVIEWED**
BUTYL-CARBITYL (6-PROPYLPIPERONYL) ETHER
**PEER REVIEWED**
ENT 14,250
**PEER REVIEWED**
FMC 5273
**PEER REVIEWED**
3,4-METHYLENEDIOXY-6-PROPYLBENZYL-N-BUTYL-DIAETHYLENGLYKOLAETHER (GERMAN)
**PEER REVIEWED**
(3,4-METHYLENEDIOXY-6-PROPYLBENZYL) (BUTYL) DIETHYLENE GLICOL ETHER
**PEER REVIEWED**
3,4-METHYLENEDIOXY-6-PROPYLBENZYL N-BUTYL DIETHYLENEGLYCOL ETHER
**PEER REVIEWED**
NCI-C02813
**PEER REVIEWED**
NIA 5273
**PEER REVIEWED**
PB
**PEER REVIEWED**
6-(PROPYLPIPERONYL)-BUTYL CARBITYL ETHER
**PEER REVIEWED**
6-PROPYLPIPERONYL BUTYL DIETHYLENE GLYCOL ETHER
**PEER REVIEWED**
5-PROPYL-4-(2,5,8-TRIOXA-DODECYL)-1,3-BENZODIOXOL (GERMAN)
**PEER REVIEWED**
PYRENONE 606
**PEER REVIEWED**
TOLUENE, ALPHA-(2-(2-BUTOXYETHOXY)ETHOXY)-4,5-(METHYLENEDIOXY)-2-PROPYL-
**PEER REVIEWED**
Formulations/Preparations:
MIXT OF PYRETHRIN & PIPERONYL BUTOXIDE REGISTERED AS PYRENONES BY FAIRFIELD AMERICA
CORP IN USA, AS PYBUTHRINS BY COOPER, MCDOUGALL & ROBERTSON LTD IN GREAT BRITAIN,
& PYROCIDES BY MCLAUGHLIN GORMLEY KING CO IN USA.
Available in various mixtures with synthetic pyrethroids, eg, Derringer, Duracide,
Grovex, Prentox, Scourge; also in combination with rotenone, qv, PB-NOX, Chem-fish,
Rotacide.
Dust, emulsifiable concentrate, fogger, paper coating, pressurized spray, solution,
wettable powder.
INGREDIENT OF INSECTICIDAL OIL SOLN, AEROSOLS, DUSTS, WETTABLE POWDERS, SLURRIES
Anvil is a pesticide product that is used to control mosquitoes ... contains sumithrin,
piperonyl butoxide and petroleum solvents.
RTECS Number:
NIOSH/XS8050000
Administrative Information:
Hazardous Substances Databank Number: 1755
Last Revision Date: 20010808
Last Review Date: Reviewed by SRP on 5/11/1995
Update History:
Field Update on 08/08/2001, 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 03/09/2000, 1 field added/edited/deleted.
Complete Update on 02/02/2000, 1 field added/edited/deleted.
Complete Update on 11/04/1999, 2 fields added/edited/deleted.
Complete Update on 09/21/1999, 1 field added/edited/deleted.
Complete Update on 08/26/1999, 1 field added/edited/deleted.
Complete Update on 03/19/1999, 1 field added/edited/deleted.
Complete Update on 06/02/1998, 1 field added/edited/deleted.
Complete Update on 03/13/1998, 2 fields added/edited/deleted.
Field Update on 10/23/1997, 1 field added/edited/deleted.
Field Update on 09/17/1997, 1 field added/edited/deleted.
Complete Update on 01/30/1997, 2 fields added/edited/deleted.
Complete Update on 06/06/1996, 1 field added/edited/deleted.
Complete Update on 01/21/1996, 1 field added/edited/deleted.
Complete Update on 09/05/1995, 51 fields added/edited/deleted.
Field Update on 05/26/1995, 1 field added/edited/deleted.
Field Update on 12/28/1994, 1 field added/edited/deleted.
Complete Update on 11/28/1994, 1 field added/edited/deleted.
Complete Update on 10/27/1994, 2 fields added/edited/deleted.
Complete Update on 03/25/1994, 1 field added/edited/deleted.
Complete Update on 09/14/1993, 1 field added/edited/deleted.
Field update on 12/22/1992, 1 field added/edited/deleted.
Complete Update on 09/03/1992, 1 field added/edited/deleted.
Complete Update on 09/26/1991, 1 field added/edited/deleted.
Complete Update on 10/22/1990, 5 fields added/edited/deleted.
Field Update on 05/14/1990, 1 field added/edited/deleted.
Field Update on 03/06/1990, 1 field added/edited/deleted.
Field Update on 03/01/1989, 1 field added/edited/deleted.
Complete Update on 04/22/1988, 3 fields added/edited/deleted.
Complete Update on 12/27/1984
Record Length: 99235