APPENDIX II-CO: Dangerous Inerts: Trimethylbenzene Added to Piperonyl
Butoxide, Cox, “Piperonyl Butoxide,” Journal of Pesticide Reform, v.22,no.2, Summer
2002.
This appendix is
copied from:
http://www.pesticide.org/PiperonylButoxide.pdf
NORTHWEST COALITION FOR ALTERNATIVES
TO PESTICIDES/NCAP
P.
O. B O X 1 3 9 3, E U G E N E, O R E G O N 9 7 4 4 0
/ ( 5 4 1 ) 3 4 4 - 5 0 4 4
JOURNAL OF
PESTICIDE REFORM/ SUMMER 2002 • VOL. 22, NO. 2
12
●
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
NORTHWEST COALITION FOR ALTERNATIVES
TO PESTICIDES/NCAP
P.
O. B O X 1 3 9 3, E U G E N E, O R E G O N 9 7 4 4 0
/ ( 5 4 1 ) 3 4 4 - 5 0 4 4
JOURNAL OF
PESTICIDE REFORM/ SUMMER 2002 • VOL. 22, NO. 2
13
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.
NORTHWEST COALITION FOR ALTERNATIVES
TO PESTICIDES/NCAP
P.
O. B O X 1 3 9 3, E U G E N E, O R E G O N 9 7 4 4 0
/ ( 5 4 1 ) 3 4 4 - 5 0 4 4
JOURNAL OF
PESTICIDE REFORM/ SUMMER 2002 • VOL. 22, NO. 2
14
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)
NORTHWEST COALITION FOR ALTERNATIVES
TO PESTICIDES/NCAP
P.
O. B O X 1 3 9 3, E U G E N E, O R E G O N 9 7 4 4 0
/ ( 5 4 1 ) 3 4 4 - 5 0 4 4
JOURNAL OF
PESTICIDE REFORM/ SUMMER 2002 • VOL. 22, NO. 2
15
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
NORTHWEST COALITION FOR ALTERNATIVES
TO PESTICIDES/NCAP
P.
O. B O X 1 3 9 3, E U G E N E, O R E G O N 9 7 4 4 0
/ ( 5 4 1 ) 3 4 4 - 5 0 4 4
JOURNAL OF
PESTICIDE REFORM/ SUMMER 2002 • VOL. 22, NO. 2
16
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
of
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:
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.
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
NORTHWEST COALITION FOR ALTERNATIVES
TO PESTICIDES/NCAP
P.
O. B O X 1 3 9 3, E U G E N E, O R E G O N 9 7 4 4 0
/ ( 5 4 1 ) 3 4 4 - 5 0 4 4
JOURNAL OF
PESTICIDE REFORM/ SUMMER 2002 • VOL. 22, NO. 2
17
(
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
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 (
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
documented
how often this exposure
occurs.
In this study, women from
northern
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
NORTHWEST COALITION FOR ALTERNATIVES
TO PESTICIDES/NCAP
P.
O. B O X 1 3 9 3, E U G E N E, O R E G O N 9 7 4 4 0
/ ( 5 4 1 ) 3 4 4 - 5 0 4 4
JOURNAL OF
PESTICIDE REFORM/ SUMMER 2002 • VOL. 22, NO. 2
18
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
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
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
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
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
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
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)
NORTHWEST COALITION FOR ALTERNATIVES
TO PESTICIDES/NCAP
P.
O. B O X 1 3 9 3, E U G E N E, O R E G O N 9 7 4 4 0
/ ( 5 4 1 ) 3 4 4 - 5 0 4 4
JOURNAL OF
PESTICIDE REFORM/ SUMMER 2002 • VOL. 22, NO. 2
19
females.87
Toxicity to Earthworms
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
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
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
and
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
(
persisted
for at least two weeks after
a
cockroach treatment on toys and in
dust in a
kindergarten.98
References
1.
Tozzi, A. 1998. A brief history of the development
of piperonyl butoxide as an insecticide synergist.
In
D.G. Jones, ed. Piperonyl butoxide:
The insecticide
synergist.
Press. Pp. 1-5.
2.
USEPA/OPP chemical ingredients database.
www.cdpr.ca.gov.
3.
Aspelin, A.L. and A.H. Grube.
1999. Pesticides
industry sales and usage: 1996 and 1997 market
estimates.
p. 20. www.epa.gov/pesticides.
4.
Farnham, A.W. 1998. The mode of action of
piperonyl butoxide with reference to studying
pesticide resistance. In D.G. Jones, ed. Piperonyl
butoxide: The insecticide synergist.
Academic Press. Pp. 199-213.
5.
Hainzal, D., L.M. Cole, and J.E. Casida.
1998.
Mechanisms
for selective toxicity of fipronil insecticide
and its sulfone
metabolite and desulfinyl
photoproduct. Chem. Res. Toxicol. 11:
1529-
1535.
6.
Levine, B.S. and S.D. Murphy. 1977. Esterase
inhibition and reactivation in relation to piperonyl
butoxide-phosphorothionate
interactions.
Toxicol. Appl. Pharmacol. 40: 379-391.
7.
Tripathi, A.M. and R.A. Agarwal.
1998. Molluscicidal
and anti-AChE activity
of tertiary mixtures
of pesticides. Arch. Environ. Contam. Toxicol.
34:
271-274.
8.
Keane, P. 1998. The use of piperonyl butoxide
in formulations for the control of pests of
humans,
domestic pets and food animals. In
D.G.
Jones,
ed. Piperonyl butoxide:
The insecticide
synergist.
300.
9.
Carpenter, L.J. and R.A. Roth. 1988. Potentiation
by piperonyl butoxide of alphanaphthylthiourea
toxicity in the isolated, perfused
rat lung. Biochem. Pharmacol. 37:
771-772.
10.
Whitmore, R.W., J.E. Kelly, and P.L. Reading.
1992.
National home and garden pesticide use
survey. Final report, vol. 1: Executive summary,
results, and recommendations. Research Triangle
Table G-1.
11.
Adgate, J.L. et al. 2000. Pesticide storage and
use patterns in
J. Exp. Anal. Environ. Epidemiol.
10: 159-
167.
12.
of pesticide use report data 2000. Indexed
by chemical. Preliminary data.
www.cdpr.ca.gov.
13.
Hodgson, E. and P.E. Levi. 1998. Interactions
of piperonyl butoxide with cytochrome P450. In
D.G.
Jones, ed. Piperonyl butoxide: The insecticide
synergist.
41-54.
14.
Federal Insecticide, Fungicide, and Rodenticide
Act
Sec. 2(m).
15.
40 Code of Federal
Regulations § 158.340.
16.
Prentiss, Inc. 1998. Material safety data sheet:
655-113 Prentox® piperonyl butoxide
technical.
www.prentiss.com/msds/pdf/655_113.pdf.
17.
World Health Organization and Food and Agricultural
Organization. 1996. Pesticide residues
in food — Evaluations 1995. [Part II]
Toxicological
and environmental.
World Health Organization. Pp.
282.
18.
Bateman, D.N. 2000. Management of pyrethroid
exposure. Clin. Toxicol. 38:
107-109.
19.
Tanaka, T. 1993. Behavioral effects of piperonyl
butoxide
in male mice. Toxicol. Lett. 69:
155-
161.
20.
Ware, G.W. 2000. The pesticide book.
CA:
Thomson Publications. p. 379.
21.
Takahashi, O. et al. 1994. Chronic toxicity studies
of piperonyl butoxide in F344 rats. Induction
of hepatocellular
carcinoma. Fund. Appl.
Pharmacol. 22: 291-303.
22.
Friedman, M.A. and L. R. Eaton. 1978. Potentiation
of methyl mercury toxicity by piperonyl
butoxide. Bull. Environ. Contam. Toxicol. 20:
9-
10.
23.
Maekawa, A. et al. 1985. Lack of evidence of
carcinogenicity of technical-grade piperonyl butoxide
in F344 rats: Selective induction of
ileocaecal
ulcers. Fd. Chem.
Toxic. 23: 675-682.
24.
Toxic Substances. 1994. EPA Id# 067501. Piperonyl
butoxide.
Review of a series 82-4
subchronic
inhalation toxicity study in rats. Memo
from J. Doherty, Health Effects Division, to A.
Reregistration Division.
22.
25.
National Cancer Institute. Undated. Cancer.gov
dictionary. www.nci.nih.gov/dictionary.
26.
Fujitani, T., Y. Tada, and M. Yoneyama.
1993.
Hepatotoxicity of piperonyl
butoxide in male F344
rats. Toxicol. 84: 171-183.
27.
Ref. #17, p. 287-288.
28.
Fujitani, T., T. Tanaka, Y. Hashimoto, and M.
Yoneyama.
1993. Subacute toxicity of piperonyl
butoxide
in ICR mice. Toxicol. 83: 93-100.
29.
Fujitani, T., Y. Tada, and M. Yoneyama.
1993.
Hepatotoxicity of piperonyl
butoxide in male F344
rats. Toxicol. 84: 171-183.
30.
Takahashi, O. et al. 1994. Chronic toxicity studies
of piperonyl butoxide in F344 rats: Induction
of hepatocellular
carcinoma. Fund. Appl.
Pharmacol. 22: 291-303.
31.
Fujitani, T. et al. 1992. Sub-acute toxicity of piperonyl
butoxide
in F344 rats. Toxicol. 72: 291-
298.
32.
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.
Apr.
28.
33.
Toxic Substances. 1995. Carcinogenicity
peer
review of piperonyl butoxide. Memo from J.
Doherty
and
to R. Keigwin,
Registration Division, and A. Dixon
and B. Sidwell, Special
Review and
Reregistration Division.
7.
34.
National Cancer Institute. Undated. Cancer.gov
dictionary. www.nci.nih.gov/dictionary.
35.
Takahashi, O. et al. 1997. Chronic toxicity studies
of piperonyl butoxide in CD-1 mice: Induction
of hepatocellular
carcinoma. Toxicol. 124:
95-103.
36.
Ref. #17, p. 291
37.
Takahashi, O. et al. 1994. Chronic toxicity studies
of piperonyl butoxide in F344 rats. Induction
of hepatocellular
carcinoma. Fund. Appl.
Pharmacol. 22: 291-303.
38.
Public Health Service. National
Toxicology Program.
2001.
9th report on
carcinogens. Safrole.
NORTHWEST COALITION FOR ALTERNATIVES
TO PESTICIDES/NCAP
P.
O. B O X 1 3 9 3, E U G E N E, O R E G O N 9 7 4 4 0
/ ( 5 4 1 ) 3 4 4 - 5 0 4 4
JOURNAL OF
PESTICIDE REFORM/ SUMMER 2002 • VOL. 22, NO. 2
20
http://ehp.niehs.nih.gov/roc/ninth/rahc/safrole.pdf.
39.
Schreiber-Deturmeny, E.M., A.M. Pauli,
and
J.L.
Pastor. 1993. Determination of safrole,
dihydro-safrole,
and chloromethyldihydrosafrole
in piperonyl butoxide by high-performance liquid
chromatography. J. Pharmaceut. Sci.
82:
813-816.
40.
Epstein, S. et al. 1967. Synergistic toxicity and
carcinogenicity of ‘Freons’
and piperonyl butoxide.
Nature 214: 526-528.
41.
Fujii, K. and S. Epstein. 1979. Effects of piperonyl
butoxide
on the toxicity and hepatocarcinogenicity
of 2-acetylaminofluorene and 4-
acetylaminobiphenyl,
and their N-hydroxylated
derivatives, following administration to newborn
mice. Oncol. 36: 105-112.
42.
Ref. #17, pp. 288-293.
43.
Breathnach, R. 1998. The safety of piperonyl
butoxide.
In D.G. Jones, ed. Piperonyl butoxide:
The insecticide
synergist.
Press. p. 23.
44.
Suzuki, H. and N. Suzuki. 1995. Piperonyl butoxide
mutagenicity
in human cells. Mut. Res.
344:
27-30.
45.
Tayama, S. 1996. Cytogenetic
effects of piperonyl
butoxide
and safrole in CHO-K1 cells. Mut.
Res. 368: 249-260.
46.
1998.
Health effects test guidelines:
OPPTS 870.5915. In vivo sister chromatid exchange
assay. www.epa.gov/pesticides.
47.
1985.
Piperonyl butoxide-mutagenicity
study submitted in response to Special Review
DCI.
Accession No. 257430. Registration No.
1021-974.
Caswell: 670. Memo from
Hazard Evaluation Div. to T. Gardner and P.
Shroeder,
Registration Div.
June
27.
48.
Ref. # 32, p. R12-13.
49.
Ref. # 43, p. 20.
50.
Tanaka, T. 1992. Effects of piperonyl butoxide
on F1 generation mice. Toxicol. Lett. 60:
83-90.
51.
Tanaka, T., O. Takahashi, and S. Oishi. 1992.
Reproductive
and neurobehavioral effects in the
three-generation toxicity study of piperonyl butoxide
administered to mice. Fd. Chem. Toxic.
30:
1015-1019.
52.
Tanaka, T. et al. 1994. Developmental toxicity
evaluation of piperonyl
butoxide in CD-1 mice.
Toxicol Lett. 71:
123-129.
53.
Toxic Substances. 1993. EPA ID # 067501.
Memo
from G.B. Reddy, Health Effects Division,
to B. Sidwell and T.
Chin, Reregistration Division..
data evaluation record, pp. 8-9.
54.
Lee, T.-P., R. Moscati, and
Effects
of pesticides on human leukocyte function.
Res. Comm. Chem. Pathol.
Pharmacol.
23:
597-609.
55.
Diel, F. et al. 1999. Pyrethroids
and piperonylbutoxide
affect human T-lymphocytes in vitro.
Toxicol. Lett. 107:
65-74.
56.
National Research Council. Commission on Life
Sciences. Board on Environmental Studies and
Toxicology. Committee on Hormonally Active
Agents in the Environment. 1999. Hormonally
active agents in the environment.
D.C.:
57.
Eubanks, M.W. 1997. Hormones and health.
Environ. Health Persp. 105: 482-487.
58.
Ref. #17, 290-291.
59.
Baynes, R.E. and J.E. Riviere.
1998. Influence
of inert ingredients in pesticide formulations on
dermal absorption of carbaryl.
AJVR 59:
168-
175.
60.
J.R. Thornton-Manning, and A.R. Dahl. 1997.
Metabolic
capacity of nasal tissue interspecies
comparisons of xenobiotic-metabolizing
enzymes.
Mut. Res. 380: 43-59.
61.
Lu, P.-Y. 1977. The environmental fate of three
carcinogens: benzo-(a)-pyrene, benzidine, and
vinyl chloride evaluated in laboratory model ecosystems.
Arch. Environ. Contam. Toxicol. 6:
129-
142.
62.
Whyatt, R.M. 2002. Residential pesticide use
during pregnancy among a cohort of urban minority
women. Environ. Health Persp.
110: 507-
514.
63.
Service. Science and Technology
Division. 1997.
Pesticide
data program: Annual summary calendar
year 1995. Appendix E. p. 9.
64.
Service. Science and Technology
Division. 1998.
Pesticide
data program: Annual summary calendar
year 1996. Appendix D. p. 23.
65.
Service. Science and Technology
Division. 1998.
Pesticide
data program: Annual summary calendar
year 1997. Appendix E. p. 23.
66.
Service. Science and Technology
Division. 2000.
Pesticide
data program: Annual summary calendar
year 1998. Appendix E. p. 29.
67.
Service. Science and Technology
Division. 2001.
Pesticide
data program: Annual summary calendar
year 1999. Appendix E. p. 30.
68.
Service. Science and Technology
Division. 2001.
Pesticide
data program: Annual summary calendar
year 2000. Appendix E. p. 39.
69.
Osimitz, T.G. and J.F. Hobson. 1998. An ecological
risk assessment of piperonyl
butoxide. In
D.G.
Jones, ed. Piperonyl butoxide: The insecticide
synergist.
122-135.
70.
Siddiqui, M.K.J. et al. 1993. Alterations in extra
hepatic glutathione S-transferase
activity in pigeon
exposed to dimethoate, piperonyl butoxide
and DDT. Indian J. Exper. Biol. 31: 278-279.
71.
Paul, E.A., and H.A. Simonin. 1995. Comparison
of the toxicity of a synergized and nonsynergized
insecticide to young trout. Bull.
Environ. Contam. Toxicol. 55:
453-460.
72.
Paul, E.A. and H.A. Simonin. 1996. Effects of
naled,
synergized and non-synergized resmethrin
on the swimming performance of young trout.
Bull. Environ. Contam. Toxicol. 57:
495-502.
73.
Miyamoto, M. et al. 1992. Effect of metabolism
on bioconcentration of
geometric isomers of dphenothrin
in fish. Chemosphere 24: 2001-2007.
74.
Erickson, D.A., F.E. Laib, and J.J. Lech. 1992.
Biotransformation
of rotenone by hepatic microsomes
following pretreatment of rainbow trout
with inducers of cytochrome
P450.
Biochem. Physiol. 42:
140-150.
75.
Reinbold, K.A. and R.L. Metcalf. 1976. Effects
of the pesticide synergist piperonyl
butoxide on
metabolism of pesticides in green sunfish.
Biochem. Physiol. 6:
401-412.
76.
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.
77.
Melancon, M.J., J. Saybolt,
and J.L. Lech. 1977.
Effect
of piperonyl butoxide on
disposition of di-
2-ethylhexyl phthalate by rainbow trout.
Xenobiotica 7: 633-640.
78.
System. Di(2-ethylhexyl)phthalate (DEHP).
www.epa.gov/iris/subst/0014.htm
79.
Meldahl, A.C., K. Nithipatikom,
and J.J. Lech.
1996.
Metabolism of several 14C-nonylphneol
isomers by rainbow trout ( Oncorhynchus mykiss):
In vivo and
in vitro microsomal metabolites.
Xenobiotica 26: 1167-1180.
80.
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.
81.
Paolucci, M., N. Custodia,
and I.P. Callard. 1998.
Progesterone
effects and receptors, subavian
species. In Knobil,
E. and J.D. Neill. Encyclopedia
of reproduction. Vol. 4.
Press. Pp. 16-23.
82.
of multiple steroid hydroxylases
in Daphnia
magna and their modulation by xenobiotics.
Environ. Toxicol. Chem. 13:
1013-1021.
83.
Hagler, J.R., G.D. Waller, and B.E. Lewis. 1989.
Mortality
of honeybees (Hymenoptera: Apidae)
exposed to permethrin and
combinations of
permethrin
with piperonyl butoxide. J. Apicult.
Res. 28: 208-211.
84.
Federle, P.F. and W.J. Collins. 1976. Insecticide
toxicity to three insects from
85.
Lindsay, R.J. and A.M. Clark. 1978. The effect
of microsomal enzyme
inhibitor, piperonyl butoxide,
on mutagenesis in Drosophila
melanogaster. (Abstract.) Mut. Res. 53: 221.
86.
Fang, N., P.E.A. Teal, and J.H. Tumlinson. 1995.
Characterization
of oxidase(s) associated with
the sex pheromone gland in Manduca sexta (L.)
females. Arch. Insect Biochem. Physiol. 29: 243-
257.
87.
Ref. # 20, p. 387.
88.
Roberts, B.L. and H.W. Dorough. 1984. Relative
toxicities of chemicals to the earthworm
Eisenia foetida. Environ. Toxicol. Chem. 3:
67-
78.
89.
Kato, H., O. Kodama, and T. Akatsuka. 1995.
Characterization
of an inducible P450 hydroxylase
involved in the rice diterpene
phytoalexin
biosynthetic pathway. Arch. Biochem.
Biophys.
316:
707-712.
90.
Tanigaki, F. 1993. Interaction of microsomal
cytochrome
P-450s
and n-phenylcarbamates that
induce flowering in Asparagus seedlings. Z.
Naturforsch. 48 c: 879-885.
91.
Simarmata, M. and D. Penner.
1993. Protection
from primisulfuron injury
to corn ( Zea mays) and
sorghum ( Sorghum bicolor) with herbicide
safeners. Weed Technol.
7: 174-179.
92.
Kotoula-Syka, E. and K.K. Hatzios.
1996. Interactions
of tribenuron with four
safeners and piperonyl
butoxide
on corn ( Zea mays). Weed Sci.
44:
215-218.
93.
Cottingham, C.K., K.K. Hatzios,
and
Meredith.
1993. Comparative responses of selected
corn ( Zea mays L.)
hybrids to EPTC and
metolachlor. Weed Res. 33:
161-170.
94.
Varsano, R. and B. Rubin. 1991. Increased herbicidal
activity of triazine
herbicides by piperonyl
butoxide. Phytoparasitica 19: 225-236.
95.
Kwon, C.S., J.J. Kells, and D. Penner.
1995.
Combined
effects of acetolactate synthase-inhibiting
herbicides with terbufos
and piperonyl
butoxide
on corn ( Zea mays) and soybean ( Glycine
max).
Weed Technol.
9: 696-702.
96.
Kwon, C. and D. Penner. 1996. The effect of
piperonyl butoxide and adjuvants on
sulfonylurea
herbicide activity. Weed Technol.
10: 127-133.
97.
Arnold, D.J. 1998. The fate and behavior of piperonyl
butoxide
in the environment. In D.G.
Jones,
ed. Piperonyl butoxide:
The insecticide
synergist.
117.
98.
Fischer, A, and T. Eikmann. 1996. Improper use
of an insecticide at a kindergarten. Toxicol. Lett.
88:
359-364.