APPENDIX II-O: Piperonyl Butoxide Factsheet:
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●
I N S E C T I C I D
E S Y N E R G I S T F A C T S H E E T
Caroline Cox is
NCAP’s staff scientist.
BY CAROLINE COX
Piperonyl
butoxide (PBO) is an
insecticide
synergist, a chemical that
is
used to make insecticides more potent.
(See
Figure 1 for PBO’s molecular
structure.)
The discovery of PBO’s
properties
as a synergist occurred in
the
1940s, following the development
of
aerosol cans to apply insecticides.1
PBO
is now frequently used, particularly
in
aerosol products. About 1700
insecticide
products contain PBO,2 8
percent
of the over 20,000 pesticide
products3
registered in the
Major
U.S. manufacturers of PBO
pesticides
include MGK (McLaughlin
Gormley
King Company), Prentiss, Inc.
and
S.C. Johnson & Son, Inc.1
PBO
is often used as a synergist
with
pyrethrins (JPR 22(1):14-20) and
the
chemically related synthetic pyrethroids.
4
However, it also can synergize
a
variety of other pesticides, including
the
insecticides fipronil,5 parathion,6
PIPERONYL BUTOXIDE
Piperonyl butoxide (PBO) is a
synergist used to increase the potency of insecticides like pyrethrins and
pyrethroids.
According to the
household pesticide products.
PBO acts as a synergist by inhibiting
the activity of a family of enzymes called P450s. These enzymes have many
functions, including breakdown of
toxic chemicals and transformation of hormones.
Symptoms
of PBO exposure include nausea, diarrhea, and labored breathing.
EPA classifies PBO as a “possible
human carcinogen” because it caused liver tumors and cancers in laboratory
tests.
In a study conducted by PBO
manufacturers, PBO caused atrophy of the testes in male rats. Other researchers
found
behavioral changes (a decrease in
home recognition behavior) in the offspring of exposed mothers.
PBO affects a variety of
hormone-related organs, including thyroid glands, adrenal glands and the
pituitary gland.
PBO reduces the immune response of
human lymphocytes, cells in our blood that help fight infections.
Concentrations of less than one part
per million of PBO reduce fish egg hatch and growth of juvenile fish. PBO also
inhibits hormone-related enzymes in
fish and slows the breakdown of toxic chemicals in their tissues. PBO is very
toxic to earthworms and highly toxic
to aquatic animals.
taining
products are
made
indoors every
year
in the U.S, and
almost
60 million
applications
outdoors.
10
In
addition to
these
household
uses,
other significant
uses
include
use
in public health
pest
control, commercial
indoor
pest control, buildings
that
house animals, commercial landscape
maintenance,
and lettuce
production.12
Mode
of Action
Piperonyl butoxide acts as a synergist
by
slowing the breakdown in
insects
of certain insecticides. The first
step
in the breakdown of many drugs,
pesticides,
and other compounds is
oxidation
by a family of enzymes called
the
P450 mono-oxygenases. PBO inhibits
the
activity of these enzymes. If
the
breakdown product is less toxic
than
the insecticide itself, the insecticide
remains
toxic longer when PBO
dichlorvos,7
linalool, and D-limonene,8
the
insect growth regulators methoprene,
hydroprene,
and fenoxycarb,8
as
well as alpha-naphthylthiourea (formerly
used
as a rodenticide).9
Use
In a household pesticide use survey
done
for the U.S. Environmental
Protection
Agency (EPA), products contained
PBO
more frequently than any
other
ingredient. Over 12 percent of
the
products used by households in
the
survey contained PBO.10 A recent
The
EPA survey estimates that almost
300
million applications of PBO-con-
Figure
1
Piperonyl
Butoxide
2-(2-butoxyethoxy)ethyl
6-propylpiperonyl ether
O
O
O
O
O
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Raid Flea Killer Plus (EPA Reg. No.
4822-273) contains
butane,
propane, and isobutane as
“inert” propellants.
1 Butane,
isobutane, and propane can cause
headache,
dizziness, numbness, sleepiness, mental confusion,
poor
coordination, and memory loss. They are
“extremely
flammable” and “will be easily ignited by
heat,
sparks, or flame.”2,3,4
Pyrenone®
Crop Spray (EPA Reg. No. 432-1033) and
Prentox®
PyronylTM Fogging &
Contact Spray (EPA Reg.
No. 655-675) contain a petroleum
solvent.5,6 This
solvent
is
called hydrotreated kerosene and
its Chemical
Abstract Service number is 64742-47-8.7
This solvent has
caused
skin tumors when applied to the skin of laboratory
mice.8
Exposure to this solvent also causes dizziness,
nausea,
and headache. Breathing droplets of this
solvent
can cause aspiration pneumonia.6
Scourge®
Insecticide with SBP-1382®/PBO 1.5%+4.5%
Forla
II (EPA Reg. No. 432-719) contains an aromatic
petroleum
solvent with Chemical Abstract Services number
64742-94-59 also
called solvent naphtha.
This solvent
contains
two aromatic hydrocarbons, naphthalene and 1,2,4-
trimethylbenzene.10
Naphthalene is classified by EPA as a
possible
human carcinogen because it causes lung tumors
in
mice following inhalation. Naphthalene exposure also
causes
headache, restlessness, lethargy, nausea, diarrhea,
and
anemia. Anemia in newborns can be caused by exposure
during
pregnancy.11 1,2,4-Trimethyl
benzene is irritating
to
eyes and skin. It can depress the central nervous
system
and cause headache, fatigue, nausea, and anxiety.
It has also caused asthmatic bronchitis.12
1.
S.C. Johnson & Son, Inc. 2000. Material safety data sheet: Raid® Flea
Killer
Plus.
2.
Hazardous Substance Data Bank. 2002. Butane. http://toxnet.nlm.nih.gov.
3.
Hazardous Substance Data Bank. 2002. Isobutane. http://
toxnet.nlm.nih.gov.
4.
Hazardous Substance Data Bank. 2001. Propane. http://toxnet.nlm.nih.gov.
5.
Aventis. 2001. Material safety data sheet: Pyrenone® Crop Spray.
www.cdms.net/ldat/mp0GC000.pdf.
6.
Prentiss, Inc. 1998. Material safety data sheet: Prentox® Pyronyl
Fogging &
Contact
Spray. www.prentiss.com/msds/pdf/655_675.pdf.
7.
National Institute for Occupational Safety and Health. Undated. The registry
of
toxic effects of chemical substances: Kerosene (petroleum),
hydrotreated.
www.cdc.gov/niosh/rtecs/oa53fc00.html.
8.
International Agency for Research on Cancer. 1989. Occupational exposures
in
petroleum refining. IARC
Monographs 45:39. http://193.51.164.11/
htdocs/monographs/Vol45/45-01.htm.
9.
Aventis. 2000. Material safety data sheet: Scourge® Insecticide with
SBP-1382®/PBO
1.5%+4.5% Forla II. www.cdms.net/ldat/mp57D000.pdf.
10.
Shell Chemical Company. 2002. Material safety data sheet: Shellsol®
A150.
www.euapps.shell.com/MSDS/GotoMsds.
11.
Hazardous Substance Data Bank. 2002. Naphthalene. http://
toxnet.nlm.nih.gov.
12.
Hazardous Substance Data Bank. 2002. 1,2,4-trimethylbenzene. http://
toxnet.nlm.nih.gov.
EXAMPLES
OF HAZARDOUS “INERTS” IN PRODUCTS
CONTAINING PIPERONYL BUTOXIDE
inhibits
the P450 enzymes.13
P450
enzymes have important biological
functions.
In addition to detoxification
of
synthetic compounds, they
also
transform sex hormones, vitamins,
and
other naturally occurring
molecules.13
Inert
Ingredients
Like most pesticides, commercial
PBO-containing
insecticides contain ingredients
other
than PBO many of
which,
according to
are
called “inert.”14 Except for
acute
toxicity
testing, all toxicology tests required
for
registration of PBO products
were
conducted with PBO, not
with
the combination of ingredients
found
in commercial products.15
Most
inert ingredients are not identified
on
product labels, and little
information
about them is publicly
available.
For
more information about the
hazards
of some of the inert ingredients
in
PBO products see “Examples
of
Hazardous ‘Inerts’,” below.
Exposure
Symptoms
Symptoms caused by ingestion of
PBO
include nausea, cramps, vomiting,
and
diarrhea.16 Symptoms caused
by
breathing PBO include tearing, salivation,
and
labored breathing.17 Accumulation
of
fluids in the lungs can
occur.18
PBO can also cause temporary
eye
and skin irritation.16
Effects
on the Nervous
System
PBO causes behavioral changes in
young
laboratory animals. A researcher
at
the
Laboratory
of Public Health observed
behavior
of mice after they had been
fed
PBO for six weeks. He found that
exposed
rats traveled longer distances
and
turned more frequently than unexposed
animals.
(See Figure 2.) The
effects
on travel distance occurred at
all
doses tested in this experiment.19
PBO
also reduces the activity of the
Figure
2
PBO
Changes Behavior
Source: Tanaka, T. 1993. Behavioral
effects
of piperonyl butoxide in male mice.
Toxicol. Lett. 69:
155-161.
Unexposed
Exposed
25
20
15
10
5
0
Distance
travelled (meters in 10 minutes)
Note:
Lines above
bars
are standard
errors.
In
a laboratory study, PBO affected motor
activity
at every dose level tested.
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enzyme
cholinesterase. This enzyme
plays
a role in transmitting nerve impulses
from
one nerve cell to another
or
to muscle cells.20 In a long-term
feeding
study with rats, researchers
from
the laboratory mentioned in the
previous
paragraph found that female
rats
fed PBO had 30 percent less blood
cholinesterase
activity than unexposed
rats.21
In
addition, PBO can increase the
neurotoxicity
of other compounds. For
example,
pharmacologists at
PBO
and methylmercury, a neurotoxic
metal.
They found that rats fed the
combination
developed neurological
symptoms
more frequently than rats
fed
methylmercury alone.22
Effects
on the Digestive
System
Researchers at the National Institute
of
Hygienic Sciences (
long-term
exposure to PBO caused
intestinal
ulcers in rats. Intestinal bleeding
was
also more common in exposed
rats
than in unexposed ones.23
Effects
on the Larynx
The larynx is susceptible to damage
from
breathing PBO-contaminated
air.
A study conducted by a manufacturers’
task
force found damage at
all
dose levels tested.24 (See Figure 3.)
The
damage consisted of metaplasia,
transformation
of cells to an atypical
form,
and hyperplasia, an abnormal
increase
in the number of cells in an
organ.25
Effects
on the Liver and
Kidney
In
laboratory toxicology studies,
PBO
often affects the liver. For example,
in
the study of the digestive
system
mentioned above, liver weights
in
all exposed rats were greater than
in
unexposed rats. The researchers also
observed
liver damage.23 Other
researchers
in
the same laboratory found
that
liver damage occurred following
as
little as one week of exposure.26 In
a
study with dogs conducted by a
manufacturers’
task force, liver damage
occurred
at all dose levels tested.27
A
similar study with a lower dose level
found
liver damage at all but the Piperonyl butoxide exposure increases
cholesterol levels.
Figure
4
Exposure
to Piperonyl Butoxide Increases Cholesterol Levels
Source:
4816-72. Piperonyl butoxide. Review of a
chronic feeding/oncogenicity study submitted by the
Piperonyl
Butoxide Task Force. Memo from J. Doherty, Hazard Evaluation Division, to P.
Hutton
and
G. Werdig, Registration Division.
0 30 100 500
200
100
0
Cholesterol
concentration(as percent of level in unexposed animals;males and females
combined)
Amount
of piperonyl butoxide consumed for 25 weeks
(milligrams
per kilogram of body weight per day)
Figure
3
Breathing
Piperonyl Butoxide Damages the Larynx
Source:
Piperonyl butoxide. Review of a series 82-4
subchronic inhalation toxicity study in rats. Memo
from
J. Doherty, Health Effects Division, to A. Dixon and B. Sidwell, Special Review
and
Reregistration
Division.
Piperonyl
butoxide damaged the larynx at all dose levels tested.
100
80
60
40
20
0
Percent
of animals with larynx lesions(metaplasia and hyperplasia,
males
and females combined)
0
0.2 0.4 0.6
Piperonyl
butoxide concentration (milligrams per liter)
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lowest
level.27 Liver damage
also occurred
in
studies with mice.28
Researchers
from the
Research
Laboratory studied effects
of
PBO on kidneys. In a threemonth
feeding
study with rats, they
found
kidney damage at all dose levels
tested.
Damage included atrophy
and
dilation of kidney structures.29
Effects
on the
Circulatory
System
Long-term feeding of PBO caused
anemia
in rats in a study conducted
by
researchers from the Tokyo Metropolitan
Research
Laboratory of Public
Health.
The amount of hemoglobin (an
oxygen-carrying
molecule in blood)
was
lower in exposed rats than unexposed
ones
at all dose levels tested.30
In
another study by the same group
of
researchers, a three-month exposure
to
PBO increased the blood levels
of
cholesterol in rats. Cholesterol
levels
at the highest dose were about
double
the level in unexposed rats.31
A
study by a manufacturers’ task
force
also found that PBO increased
cholesterol.
Rats exposed in a longterm
study
had higher cholesterol levels
than
unexposed rats at all but the
lowest
dose tested.32 (See Figure 4.)
Carcinogenicity
Since 1995, EPA has classified piperonyl
butoxide
as carcinogen (a
chemical
that causes cancer). EPA’s
classification
of piperonyl butoxide is
“Group
C,” a possible human carcinogen.
EPA
based its evaluation on a
study
of mice conducted by a
manufacturers’
task force. The study
found
that piperonyl butoxide caused
liver
tumors and cancer.33,34 (See
Figure
5.)
PBO
also caused liver cancer in
mice
in a study conducted by researchers
from
the
Laboratory.
At the highest dose
level,
almost half of the mice tested
developed
liver cancer.35
PBO
has also caused cancer in rats.
A
study conducted by PBO manufacturers
found
the incidence of lymph
and
thyroid tumors increased with increasing
exposure
to PBO.36 A second
study,
by the Japanese researchers
mentioned
above, found that PBO
Figure
5
Exposure
to Piperonyl Butoxide Causes Cancer
Source:
Carcinogenicity peer review of piperonyl
butoxide. Memo from J. Doherty and E. Rinde , Health
Effects
Division, to R. Keigwin, Registration Division, and A. Dixon and B. Sidwell,
Special
Review
and Reregistration Division.
35
30
25
20
15
10
5
0
EPA
classifies PBO as a carcinogen because it causes liver tumors and cancer.
Percent
of animals with liver tumors and cancer(both sexes combined)
0 100 200 300
Amount
of piperonyl butoxide consumed
(milligrams
per kilogram of body weight per day)
caused
liver cancer.37
A
contaminant of PBO causes cancer.
The
contaminant is safrole, which
the
National Toxicology Program classifies
as
“reasonably anticipated to be
a
human carcinogen.”38 Researchers at
the
UFR de Pharmacie (France) found
safrole
in all of the PBO samples they
tested.
The samples were provided
by
European manufacturers.39
In
addition, PBO can increase the
carcinogenicity
of other cancer-causing
chemicals.
Researchers at Harvard
Institute
found that the combination
of
Freon (a refrigerant that was
also
used as a propellant in aerosol
pesticides)
and PBO was more carcinogenic
than
either chemical alone.40
The
liver carcinogen N-hydroxy-2-
acetylaminofluorene
also is more carcinogenic
when
combined with PBO
than
it is alone.41
However,
the carcinogenicity of PBO
is
still controversial to some reviewers.
The
World Health Organization, in a
1995
review, identified five other
studies
that found no evidence that
PBO
exposure caused cancer.42
Mutagenicity
(Genetic Damage)
While
some tests for genetic damage
have
shown that PBO “does not demonstrate
any
significant potential for
mutagenicity,”43
this synergist does
cause
genetic damage in other tests.
In
1995, researchers from the
Metropolitan
Research Laboratory of
Public
Health studied PBO’s effects
on
a cell culture derived from human
embryo
cells. They found that
PBO
caused mutations in a gene
called
OuaR.
Also, PBO caused mutations
in
K-ras,
a gene “believed to
be
involved in neoplastic [tumorous]
changes.”44
Another
study from the same
laboratory
found that PBO caused sister
chromatid
exchanges in cultures of
cells
from hamster ovaries.45 (Sister
chromatid
exchanges are exchanges of
genetic
material within a chromosome.46)
PBO’s
contaminant safrole also
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caused
sister chromatid exchanges in
this
study.45
In
addition, a study conducted by a
PBO
manufacturer found that the frequency
of
a mutation called HGPRT
was
2 to 4 times higher in hamster
ovary
cells exposed to PBO than in
unexposed
cells. However, EPA agreed
with
the study authors that this was
“not
of biological significance.”47
Effects
on Reproduction
In laboratory tests, PBO has adversely
affected
a variety of reproductive
functions.
Atrophy
of the testes was observed
in
a two-year feeding study with rats
conducted
by a manufacturers’ task
force,48
along with some decreases in
weight
of the seminal vesicles (spermproducing
structures).49
(See Figure 6.)
Increased
incidence of testicular atrophy
occurred
at all dose levels tested.
However,
because the average weight
of
the testes did not decrease, EPA
concluded
that “the data did not
provide
conclusive evidence.”48
A
series of studies at the
Metropolitan
Research Laboratory
found
other effects on reproduction.
The
offspring of mice that were fed
PBO
before, during, and after pregnancy
weighed
less than the offspring
of
unexposed mice. This decrease occurred
at
all the dose levels tested in
this
experiment. In addition, PBO
caused
changes in the home recognition
olfactory
behavior of the offspring
of
exposed mothers. In a test where
the
mice had a choice of entering a
compartment
with wood chips from
their
home cage or entering a compartment
with
fresh (unused) chips,
the
offspring of exposed mothers were
less
likely to enter the compartment
that
smelled like home than the offspring
of
unexposed mothers. This
behavioral
change occurred at all but
the
lowest dose level tested.50
A
three-generation study by researchers
from
the same laboratory
found
that litter size and weight were
less
for exposed mothers than for unexposed
ones.
(Animals were fed PBO
continuously
from an age of 5 days in
the
first generation through the weaning
of
the third generation.) Also, nursing
pups
of exposed mothers weighed
less
than pups with unexposed
mothers.
In the third generation, several
behaviors,
including the olfactory
home-recognition
behavior mentioned
above,
were also affected by PBO exposure.
The
effects on the weight of
nursing
pups occurred at all dose levels
tested,
the behavioral effects occurred
at
all but the lowest dose
level.51
A
third study from the same laboratory
used
a different kind of exposure.
In
this study, pregnant mice were
given
a single dose of PBO on the
ninth
day of their pregnancy. The
weight
of fetuses from exposed mothers
was
less than the weight of fetuses
from
unexposed mothers. This
effect
occurred at all dose levels tested
for
female fetuses and all but the lowest
dose
level for males. The number
of
fetal deaths was also higher for exposed
mothers.
These increased fetal
deaths
occurred at all but the lowest
dose
level tested. These researchers
also
found that the frequency of fetuses
with
defective or missing fingers
was
higher for mothers exposed at all
but
the lowest dose level.52
A
study conducted by a manufacturers’
task
force found that the incidence
of
a bone defect was higher
in
the offspring of rats exposed during
pregnancy
than in the offspring of
unexposed
rats. The incidence was
dose-related
and was 2 to 4 times
higher
for exposed rats than for unexposed
ones.
However, EPA concurred
“with
the study author’s conclusions
that
these effects were not related to
treatment.”53
Effects
on the Immune
System
Medical researchers first documented
PBO’s
ability to inhibit normal
functions
of the immune system in
1979.
Physicians from the State University
of
New York (Buffalo) showed
that
PBO inhibited the immune response
of
human blood cells called
lymphocytes.
PBO caused stronger inhibition
(25
percent) than the seven
other
pesticide chemicals tested.54
In
a recent (1999) study, researchers
from
the University of Applied Sciences
Figure
6
Exposure
to Piperonyl Butoxide Causes Atrophied Testes
Source:
U.S. EPA. Office of Prevention, Pesticides and Toxic Substances. 1988. EPA Reg.
No.:
4816-72. Piperonyl butoxide. Review of a
chronic feeding/oncogenicity study submitted by the
Piperonyl
Butoxide Task Force. Memo from J. Doherty, Hazard Evaluation Division, to P.
Hutton
and
G. Werdig, Registration Division. Washington, D.C., Apr. 28. p. R12-R13.
Number
of animals with bilateral testicular atrophy(both right and left testes
damaged)
30
20
10
0
Piperonyl
butoxide caused atrophied testes in a long-term feeding study of rats.
Amount
of piperonyl butoxide consumed
(milligrams
per kilogram of body weight per day)
0
30 100 500
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(Germany)
found similar results: PBO
caused
about a 50 percent reduction
in
the immune response of human
lymphocytes.55
(See Figure 7.)
Effects
on Hormones
The impact of environmental contaminants
on
the normal function of
human
and animal hormone systems
has
been a significant concern in the
last
decade.56 Hormones are
biologically
active
molecules that control all
responses
and functions of the body.
Dramatic
changes in the activity of cells
in
humans and other animals “are
caused
by extremely small amounts”
of
hormones or other chemicals that
disrupt
this system.57
Since
the P450 enzymes inhibited
by
PBO break down steroids (a class
of
chemicals that includes many sex
hormones),13
it is not surprising that
PBO
can have this kind of hormonal
effect.
A study conducted by a task
force
of PBO manufacturers showed
that
long-term exposure of rats to PBO
damages
hormone-related organs. In
exposed
animals, thyroid glands were
larger
than in unexposed animals. Also,
adrenal
glands in exposed females
were
larger than in unexposed females,
and
pituitary glands were smaller in
exposed
males.58
Increasing
Exposure to
Potentially
Toxic Chemicals
PBO can increase exposure of
people
and other species to toxic
chemicals
in several different ways.
First,
this synergist affects the
amount
of certain toxic chemicals that
are
absorbed through skin. Veterinarians
at
North Carolina State University
found
that PBO exposure increased
the
absorption of the insecticide carbaryl
through
skin. When exposure to
PBO
occurred, skin absorption was
about
double the rate without PBO
exposure.
The veterinarians believe
that
the increased absorption was
caused
by PBO’s ability to irritate the
skin.59
Second,
PBO can inhibit the activity
of
P450 enzymes in the nose that
would
otherwise detoxify chemicals
that
are inhaled. Researchers from the
Lovelace
Respiratory Institute showed
that
high levels of detoxifying enzymes
occur
in the noses of many species,
and
some of these enzymes are
inhibited
by PBO.60
Finally,
PBO can inhibit the breakdown
of
toxic chemicals in the soil by
inhibiting
the enzymes in microorganisms
that
usually do the detoxification.
For
example, researchers at the
Institute
for Environmental Studies (Illinois)
found
that about 1 1/2 times as
much
benzidine, a carcinogen, persisted
for
a month when the soil was
treated
with both benzidine and PBO
as
persisted when the treatment used
only
benzidine.61
Exposure
Because PBO is frequently used for
household
pesticide treatments, people
are
frequently exposed. A recent (2002)
study
of pregnant women conducted
by
researchers from Columbia University
documented
how often this exposure
occurs.
In this study, women from
northern
Manhattan and the South
Bronx
(New York) wore personal air
monitors
for two days and left the
monitor
near their beds at night. The
monitoring
found PBO in air samples
from
over 80 percent of women in the
study.
PBO was the fourth most com-
Contamination
of Food
PBO
is regularly found on food.
The
U.S. Department of Agriculture has
found
PBO on spinach,63 peas, sweet
potatoes,64
tomatoes, peaches,
squash,65
strawberries,66 bell
peppers,67
grapes,
and pineapples.68
Effects
on Birds
According to a study conducted by
a
manufacturers’ task force, PBO
adversely
affected reproduction in mallard
ducks.
PBO affected the number
of
eggs laid, the number of eggs that
cracked
while being hatched, and the
Figure
7
Piperonyl
Inhibits Immune System Function
Proliferation
of lymphocytes in response tostimulation by phytohemagglutinin(percent of
unexposed cells)
100
80
60
40
20
0
Unexposed
Source:
Diel, F. et al. 1999. Pyrethroids and piperonyl-butoxide affect human
T-lymphocytes in
vitro.
Toxicol. Lett. 107:
65-74.
Piperonyl
butoxide reduces the activity of immune system cells in human blood.
Exposed
“The
monitoring
found PBO in air
samples from
over 80 percent
of the women in
the study.”
monly
detected pesticide. PBO concentrations
were
highest in homes that
had
been treated with insecticide aerosol
spray
cans or “bombs.”62
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thickness
of the eggshells.69
Researchers
from the Indian Institute
of
Chemical Technology found
that
PBO inhibited “important detoxification
enzymes”
in the kidney, lung,
brain,
and heart of pigeons. These enzymes
“protect
the cell against chemically
induced
damages” so that inhibition
of
their activity could make the
birds
more susceptible to a variety of
toxic
chemicals.70
Effects
on Fish
In terms of its acute toxicity (ability
to
cause mortality in a time period up
to
96 hours long), PBO is classified as
“moderately
toxic” to fish. Concentrations
between
3 and 7 parts per million
(ppm)
are sufficient to kill fish.69
PBO
affects the ability of fish to
successfully
reproduce at much lower
concentrations
than are required for
mortality.
In a study conducted by a
manufacturers’
task force, concentrations
of
less than 1 ppm reduced egg
hatch
and larval growth in the fathead
minnow,
a standard test fish.69
PBO
also increases the toxicity to
fish
of a variety of pesticides. For example,
studies
done by the New York
Department
of Environmental Conservation
found
that, compared to fish
exposed
to the insecticide resmethrin
alone,
mortality was higher and swimming
stamina
less in fish exposed to
both
PBO and resmethrin.71,72 PBO
also
increased bioconcentration of the
insecticide
phenothrin in a study of
carp
conducted by the Sumitomo
Chemical
Co., Ltd.73 Other studies
(by
researchers
at the University of Wisconsin-
History
Survey) found that PBO
decreased
the ability of fish to detoxify
the
pesticides rotenone, aldrin, methoxychlor,
and
trifluralin.74,75
PBO
increases the toxicity of other
chemicals
to fish. A study from the
University
of Utrecht (The Netherlands)
found
that PBO slowed the transformation
of
the dioxin 2,8-DCDD (a
chemical
relative of the notorious
2,3,7,8-TCDD)
into a form that goldfish
can
eliminate.76 This resulted
in
higher
bioaccumulation of the dioxin.
(See
Figure 8.) Researchers at the Medical
College
of Wisconsin found that
PBO
inhibited the breakdown of di-2-
ethylhexyl
phthalate77 (DEHP, a
chemical
that
causes cancer and genetic damage)
78
and nonyl phenol (an estrogen
mimic
that disrupts normal hormone
function)
in rainbow trout.79
In
addition, PBO can disrupt fish
hormone
systems. Researchers from
Oregon
State University showed that
PBO
strongly inhibits the activity of
an
enzyme called progesterone-6ß-hydroxylase
in
rainbow trout livers.80 (See
Figure
8.) Progesterone regulates egg
maturation
in fish.81
Effects
on Other Aquatic
Animals
PBO is “highly” acutely toxic to
water
fleas, shrimp and oysters. Studies
conducted
by a manufacturers’ task
force
found that concentrations of less
than
one ppm killed all three of these
species.69
Another
of the task force’s studies
found
adverse effects on water flea
reproduction
at concentrations as low
as
12 parts per billion.69 Supporting
these
results, a study from North Carolina
State
University found that exposure
of
water fleas to PBO altered the
transformation
of the sex hormone
testosterone.
Less than one ppm
inhibited
most enzymes that transform
testosterone
over 60 percent.82
Effects
on Insects
In addition to making other insecticides
more
toxic to pest insects, PBO
can
increase the toxicity of insecticides
to
beneficial insects, such as honey
bees
and water beetles.83,84
PBO
also has more unexpected effects.
Researchers
from the University
of
exposure
of fruit flies increased the
genetic
damage caused by X-rays and
the
mutagenic chemical heliotrine.85
U.S.
Dept. of Agriculture researchers
showed
that PBO inhibits the activity
of
enzymes involved in the breakdown
or
synthesis of insect sex pheromones,
86
chemicals insects use for
communication
between males and
Figure
8
Effects
of Piperonyl Butoxide on Fish
Sources:
Sijm, D.T.H.M., G. Schaap, and A. Opperhuizen.
1993. The effect of the biotransformation
inhibitor
piperonyl butoxide on the bioconcentration of 2,8-dichlorodibenzo-p-dioxin and
pentachlorobenzene
in goldfish. Aquat.
Toxicol. 27: 345-360.
Miranda, C.L., M.C. Henderson, and D.R. Buhler.
1998. Evaluation of chemicals as inhibitors of
trout
cytochrome P450s. Toxicol.
Appl. Pharmacol. 148: 237-244.
100
80
60
40
20
0
Piperonyl
butoxide can disrupt fish hormone systems and increase the concentration of
toxic
chemicals
in fish tissues.
Bioconcentration
of a dioxin
Activity
of a hormonetransforming
enzyme
Bioconcentration
factor(concentration in fish/concentration in water)
150
100
50
0
Unexposed
Exposed Unexposed Exposed
Activity
of progesterone-6Â-hydroxylase(percent of the activity
in unexposed cells)
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females.87
Toxicity
to Earthworms
University of Kentucky researchers
tested
the acute toxicity of a variety of
chemicals
to a common earthworm,
Eisenia foetida. They found
that piperonyl
butoxide
was “very toxic” to
this
earthworm.88
Effects
on Plants
Although it is perhaps unexpected
for
a chemical usually used as an insecticide
synergist,
PBO can affect plant
physiology.
For example, researchers
at
Ibaraki University (Japan) found that
PBO
inhibited P450 enzymes in rice
leaves
that produce phytoalexins, compounds
that
inhibit the germination of
disease-causing
fungus spores.89 PBO
causes
flowering in asparagus, also by
inhibiting
P450 enzymes.90
PBO
also increases herbicide damage
to
plants. It increases the damage
to
corn caused by the sulfonylurea
herbicides
primisulfuron91 and
tribenuron,92
the thiocarbamate herbicide
EPTC,93
and the triazine herbicides
atrazine,
terbutryn, and prometryn.
94
Similar increases in the toxicity
of
sulfonylurea herbicides have
been
documented in soybeans,
lambsquarter,
and a variety of weedy
grasses.95,96
Persistence
Outdoors: PBO’s
half-life (the time
required
for half of applied PBO to
break
down or move away from the
application
site) is about 4 days in
field
tests of agricultural soils conducted
by
a manufacturers’ task force.
In
the same tests, conducted in California,
Georgia,
and Michigan, PBO
persisted
(measured as the time required
for
all applied PBO to dissipate)
up
to 30 days.97
The
manufacturers’ task force also
measured
PBO’s half-life and persistence
in
water and aquatic sediments.
In
water tested in California, Arkansas,
and
Mississippi, the half-life was
about
a day. In sediments, the halflife
was
up to 24 days and PBO
persisted
up to 120 days.97
Indoors:
There is less information
available
about PBO’s persistence indoors,
but
a study from Justus Liebig
University
(Germany) found that PBO
persisted
for at least two weeks after
a
cockroach treatment on toys and in
dust
in a kindergarten.98
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