UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
MEMORANDUM
February
21,
2006
SUBJECT:
Piperonyl
Butoxide
HED
Revised
Risk
Assessment
for
Reregistration
Eligibility
Document
(
RED)
PC
Code
No
067501;
DP
Barcode
No.
326576
FROM:
Becky
Daiss
Environmental
Health
Scientist
Reregistration
Branch
4
Health
Effects
Division
(
7509C)

THROUGH:
Susan
V.
Hummel
Branch
Senior
Scientist
Reregistration
Branch
4
Health
Effects
Division
(
7509C)

TO:
Cathryn
O'Connell
Chemical
Review
Manager
Reregistration
Branch
2
Special
Review
and
Registration
Division
(
7508C)

Attached
is
Health
Effects
Division's
(
HED's)
risk
assessment
of
piperonyl
butoxide
for
purposes
of
issuing
a
Reregistration
Eligibility
Decision
(
RED)
Document
for
this
active
ingredient.
This
document
updates
the
September
8,
2005
Piperonyl
Butoxide
HED
Risk
Assessment.
The
risk
assessment
has
been
revised
to
address
public
comments.
The
revised
disciplinary
science
chapters
and
other
supporting
documents
are
included
as
appendices
as
follows:

Report
of
the
Hazard
Identification
Assessment
Review
Committee,
S.
Ramasamy
(
TXR
No.
0052600,
6/
8/
04)
(
Note:
This
is
an
archive
data
base
document
which
cannot
be
revised.
Revisions
to
the
toxicology
assessment
have
been
addressed
in
the
Risk
Assessment)
Report
of
the
Metabolism
Assessment
Review
Committee,
T
Morton,
S.
Ramasamy,
W.
Eckel
(
D321269,
9/
1/
05)
Product
&
Residue
Chemistry
Assessment,
T.
Morton
(
D310030,
11/
23/
04)
Occupational
and
Residential
Exposure
Assessment,
B.
Daiss
(
D318743,
9/
7/
05),
Occupational
and
Residential
Exposure
Assessment
for
the
Use
of
Piperonyl
Butoxide
in
Residential
Outdoor
Automatic
Mister
Systems,
M.
Crowley
(
D315334,
8/
30/
05)
Dietary
Exposure
and
Risk
Estimates
for
Tolerance
Reassessment,
T.
Morton
(
D310032,
11/
23/
04)
Review
of
Pyrethrins
Incident
Reports
­
Second
Revision,
J.
Blondell,
Ph.
D
(
D320300,
8/
16/
04)
Tier
I
Drinking
Water
Assessment,
William
Eckel
(
D286223,
5/
17/
04)
Page
2
of
61
TABLE
OF
CONTENTS
pg.
1.0
EXECUTIVE
SUMMARY
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
3
2.0
PHYSICAL/
CHEMICAL
PROPERTIES
CHARACTERIZATION
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
8
3.0
HAZARD
CHARACTERIZATION
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
9
3.1
Hazard
Profile
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
9
3.1.1
Toxicity
Profile
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
10
3.1.2
Hazard
Characterization
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
15
3.2
FQPA
Considerations
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
17
3.3
Dose
Response
Assessment
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
18
3.3.1
Dietary
Exposure
Endpoints
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
19
3.3.2
Occupational
and
Residential
Exposure
Endpoints
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
20
3.4
Endocrine
Disruptor
Effects
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
22
4.0
DIETARY
&
DRINKING
WATER
EXPOSURE/
RISK
ASSESSMENT
.
.
.
.
.
.
.
.
.
.
22
4.1
Summary
of
Registered
Uses
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
22
4.2
Dietary
Exposure/
Risk
Pathway
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
23
4.2.1
Residue
Profile
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
23
4.2.2
Dietary
Exposure/
Risk
Assessment
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
29
4.3
Drinking
Water
Exposure/
Risk
Pathway
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
31
4.3.1
Environmental
Fate
Assessment
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
31
4.3.2
Estimated
Environmental
Concentrations
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
31
5.0
RESIDENTIAL
EXPOSURE/
RISK
ASSESSMENT
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
33
5.1
Residential
Exposure
Scenarios
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
33
5.1.1
Handler
Exposure
Scenarios
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
34
5.1.2
Post­
application
Exposure
Scenarios
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
34
5.2
Residential
Exposure
Data
and
Assumptions
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
34
5.2.1
Application
Parameters
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
34
5.2.2
Handler
Exposure
Data
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
35
5.2.3
Post­
application
Exposure
Data
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
35
5.2.4
Exposure
Assumptions
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
36
5.3
Residential
Exposure
and
Risk
Estimates
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
39
6.0
AGGREGATE
RISK
ASSESSMENT
AND
RISK
CHARACTERIZATION
.
.
.
.
.
.
.
.
39
6.1
Acute
Aggregate
Risk
Assessment
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
40
6.2
Short­
term
Aggregate
Risk
Assessment
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
41
6.3
Chronic
Aggregate
Risk
Assessment
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
41
7.0
CUMULATIVE
EXPOSURE
AND
RISK
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
42
8.0
OCCUPATIONAL
EXPOSURE/
RISK
ASSESSMENT
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
43
8.1
Occupational
Exposure
Scenarios
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
43
8.1.1
Agricultural
Handler
Scenarios
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
43
8.1.2
Pest
Control
Operator
Handler
Scenarios
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
44
8.1.3
Mosquito
Abatement
Handler
Scenarios
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
44
8.1.4
Direct
Application
to
Pets
and
Farm
Animals
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
44
8.2
Occupational
Exposure
Data
and
Assumptions
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
45
8.2.1
Exposure
Data
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
45
8.2.2
Exposure
Assumptions
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
45
8.3
Occupational
Exposure
and
Risk
Estimates
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
47
9.0
INCIDENT
REPORT
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
49
10.0
UNCERTAINTIES
AND
RISK
CHARACTERIZATION
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
49
11.0
DATA
NEEDS
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
51
11.1
Product
Chemistry
Data
Requirements
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
51
Page
3
of
61
11.2
Residue
Chemistry
Data
Requirements
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
52
1.0
EXECUTIVE
SUMMARY
This
assessment
provides
information
to
support
the
issuance
of
a
risk
management
decision
document
known
as
a
Reregistration
Eligibility
Decision
(
RED)
Document
for
piperonyl
butoxide.
EPA's
pesticide
reregistration
process
provides
for
the
review
of
older
pesticides
(
those
initially
registered
prior
to
November
1984)
under
the
Federal
Insecticide,
Fungicide,
and
Rodenticide
Act
(
FIFRA)
to
ensure
that
they
meet
current
scientific
and
regulatory
standards.
The
process
considers
the
human
health
and
ecological
effects
of
pesticides
and
incorporates
a
reassessment
of
tolerances
(
pesticide
residue
limits
in
food)
to
ensure
that
they
meet
the
safety
standard
established
by
the
Food
Quality
Protection
Act
(
FQPA)
of
1996.

Use
Profile
Piperonyl
butoxide
is
an
insecticide
synergist.
Synergists
are
chemicals
that
lack
pesticidal
effects
of
their
own
but
enhance
the
pesticidal
properties
of
other
chemicals.
Piperonyl
butoxide
is
used
in
combination
with
a
wide
variety
of
insecticides
in
ratios
ranging
from
3:
1
to
20:
1
by
weight.
It
is
usually
formulated
with
natural
pyrethrins
or
synthetic
pyrethroids
and
is
an
ingredient
in
1600
to
1700
registered
pest
control
products.
It
has
numerous
and
varied
commercial
and
residential
applications,
is
available
in
a
broad
range
of
formulations,
and
is
applied
by
wide
variety
of
application
methods.
Commercial
uses
include
pre­
and
post­
harvest
application
to
food
and
non­
food
agricultural
crops,
applications
in
food
and
non­
food
handling
commercial
and
agricultural
structures
and
outdoor
premises,
housing
for
veterinary
and
farm
animals,
and
direct
application
to
veterinary
and
farm
animals.
Piperonyl
butoxide
currently
has
70
tolerances
(
40
CFR
180.127)
in/
on
various
crop
and
livestock
food
commodities.
Residentially,
it
is
used
to
control
insects
both
inside
the
home,
and
outside
on
gardens,
lawns
and
ornamentals,
patios,
and
other
outdoor
structures,
and
is
directly
applied
to
pets.
As
a
synergist,
it
inhibits
the
mixed
function
oxidase
system
of
insects
and
reduces
the
oxidative
breakdown
of
other
pesticides
like
pyrethrum
and
synthetic
pyrethroids.
Comprehensive
information
on
use
patterns
and
formulations
is
provided
in
the
Piperonyl
Butoxide
Master
Label
which
was
submitted
to
the
EPA
by
the
Piperonyl
Butoxide
Task
Force
II.
The
risk
assessments
for
piperonyl
butoxide
are
based
solely
on
the
Master
Label,
since
it
only
lists
the
uses
that
the
Task
Force
II
are
supporting
(
C.
Rodia,
Use
Closure
Memo,
11/
17/
03).

Screening
level
estimate
of
piperonyl
butoxide
usage
performed
by
HED's
Biological
and
Economical
Analysis
Division
(
BEAD)
indicates
that
5,000
to
10,000
pounds
of
piperonyl
butoxide
are
used
annually
in
the
U.
S.
for
application
to
agricultural
crops,
with
highest
usage
on
potatoes
(
30%
crop
treated)
and
other
uses
at
5%
or
less.
An
estimated
100,000
to
200,000
pounds
are
used
annually
for
non­
crop
uses.

Regulatory
History
Page
4
of
61
Piperonyl
butoxide
is
a
FIFRA
List
B
reregistration
pesticide.
The
Phase
4
Reviews
of
available
residue
chemistry
data
were
issued
in
February,
1991.
Data­
Call­
In
Notices
for
piperonyl
butoxide
were
issued
in
May,
1991
and
September,
1995
requiring
the
registrants
to
submit
several
residue
chemistry
studies
in
order
to
fulfill
reregistration
requirements.
Reregistration
of
piperonyl
butoxide
is
being
supported
by
the
Piperonyl
Butoxide
Task
Force
II,
whose
members
are
Prentiss,
Inc.,
McLaughlin
Gormley
King
Co.,
S.
C.
Johnson
&
Son,
Inc.,
Takasago
International
Corp.,
Endura
S.
p.
A.,
and
Valent
Biosciences
Corp.
Data
has
been
submitted
in
response
to
data
deficiencies
outlined
in
the
Phase
4
Reviews;
to
date,
all
studies
have
been
reviewed.

Hazard
Identification
and
Dose
Response
Assessment
The
toxicology
data
base
is
adequate
to
characterize
the
toxicity
of
piperonyl
butoxide.
Piperonyl
butoxide
has
a
low
acute
toxicity
by
oral,
inhalation
and
dermal
routes
and
it
has
been
assigned
toxicity
Category
IV
by
all
exposure
routes.
In
the
acute
studies,
piperonyl
butoxide
has
been
identified
as
minimally
irritating
to
eyes
and
skin.

The
liver
is
primary
target
organ
for
piperonyl
butoxide
induced
toxicity.
Subchronic
studies
in
rats
showed
increases
in
liver
weight,
increases
in
cholesterol
and
gamma
glutamyl
transpeptidase
activity,
and
histopathological
effects
such
as
enlargement
of
hepatocytes,
oval
cell
proliferation,
bile
duct
hyperplasia,
and
focal
necrosis.
Similar
effects
occurred
in
subchronic
mice
study
after
20
days.
The
liver
effects
(
increased
liver
weight,
focal
hyperplasia
and
changes
in
clinical
parameters)
appeared
pronounced
upon
chronic
exposure
to
piperonyl
butoxide
in
rodents
and
dogs.

In
a
subchronic
dermal
toxicity
study
in
rabbits,
no
systemic
treatment
related
effects
were
observed.
However,
piperonyl
butoxide
was
observed
to
be
a
mild
irritant
i.
e.,
macro
and
micropathology
of
the
tested
sites
exhibited
dermal
lesions
associated
with
irritation.
A
subchronic
inhalation
toxicity
study
in
rats
showed
histopathological
changes
in
the
respiratory
tract
indicated
by
metaplasia/
hyperplasia
in
the
larynx
in
all
treated
groups.

In
a
combined
chronic/
carcinogenic
study
in
rats,
positive
carcinogenic
effects
were
reported
at
doses
where
high
incidence
of
ileocaecal
ulcers
were
noticed.
Liver
adenomas
and
carcinomas
were
reported
in
Fischer
344
rats
only
when
tested
at
excessive
doses.
A
slight
increase
in
thyroid
follicular
cell
tumor
alone
was
reported
in
Sprague
Dawley
rats
when
tested
at
adequate
doses.
A
1979
National
Toxicology
Program
(
NTP)
study
reported
negative
effects
for
carcinogenicity
in
same
strain
of
rats
and
in
B6C3F1
mice.
However,
in
CD­
1
mice,
piperonyl
butoxide
tested
positive
for
liver
tumor
effects.
Piperonyl
butoxide
is
classified
as
a
Group
Cpossible
human
carcinogen
with
no
cancer
quantification
required
for
piperonyl
butoxide
risk
assessment.

The
toxicity
database
is
considered
adequate
for
evaluation
of
risks
to
infants
and
children.
Studies
indicate
that
there
is
a
low
degree
of
concern
for
fetal
susceptibility
effects
and
no
Page
5
of
61
evidence
of
residual
uncertainties
for
pre­
and
post­
natal
toxicity
from
exposure
to
piperonyl
butoxide.
No
developmental
toxic
effects
were
noted
in
guideline
studies
in
rats
and
rabbits.
Neurotoxic
effects
are
not
evident
from
the
clinical
signs
reported
in
guideline
developmental,
reproductive
and
chronic
studies.
Therefore,
the
special
FQPA
safety
factor
is
reduced
from
10x
to
1x.

Piperonyl
butoxide
tested
negative
in
bacterial
gene
mutation
assays.
The
in
vitro
mammalian
cell
mutation
assays
indicate
a
questionable
positive
effect
for
mutation.
Piperonyl
butoxide
tested
negative
for
chromosomal
aberration
and
sister
chromatid
exchange
in
CHO
cells
and
no
induction
of
unscheduled
DNA
synthesis
was
observed
in
rat
primary
hepatocytes.

Piperonyl
butoxide
is
well
known
to
inhibit
microsomal
enzymes
in
insects.
It
also
inhibits
the
microsomal
enzymes
in
several
other
species
(
e.
g.,
rats,
rabbits,
mice).
In
the
mammalian
system,
it
is
shown
to
exhibit
initial
inhibition
followed
by
stimulation
of
microsomal
enzymes
upon
continued
exposure.
The
kinetics
of
piperonyl
butoxide
inhibition
and/
or
stimulation
of
microsomal
enzymes
in
humans
is
not
established.
However,
one
study
in
humans
reports
no
inhibition
of
microsomal
enzymes
(
measured
as
antipyrine
half­
life
in
blood)
at
a
dose
of
0.7
mg/
kg.

Metabolism
studies
show
the
main
route
of
piperonyl
butoxide
excretion
in
rats
is
via
urine
and
feces
(
64­
85%
in
feces,
11­
30%
in
urine)
with
the
majority
of
the
radioactivity
being
excreted
within
48
hours.
The
parent
and
the
M3
metabolite
(
parent
with
opened
methylene
dioxy
ring)
were
the
major
compounds
identified
in
feces
(
approximately
20%
of
the
radioactivity
each).

Dietary,
drinking
water,
and
occupational
and
residential
exposure
scenarios
are
the
relevant
scenarios
for
exposure
to
piperonyl
butoxide.
The
acute
oral
endpoint
was
selected
based
on
a
developmental
toxicity
study
in
rats.
The
chronic
oral
endpoint
was
selected
based
on
a
chronic
oral
toxicity
study
in
dogs.
No
dose
or
endpoints
were
selected
for
dermal
exposure
because
no
systemic
effects
were
observed
at
the
limit
dose
in
the
21­
day
dermal
toxicity
study
in
rabbits.
The
short­,
intermediate­
term
and
long­
term
inhalation
endpoints
were
selected
based
on
a
subchronic
inhalation
study
in
rats.
Short
and
intermediate
term
incidental
oral
endpoints
were
selected
based
on
a
two
generation
reproduction
study
in
rats.
Endpoints
used
in
the
assessment
are
provided
in
Table
1.

Table
1.
Endpoints
Used
for
Piperonyl
Butoxide
Risk
Assessment
Dietary
NOAEL
mg/
kg/
day
RfD
mg/
kg/
day
PAD
mg/
kg/
day
acute
­
all
populations
630
6.3
(
UF=
100;
FQPA
=
1)
6.3
chronic
­
all
populations
15.5
0.155
(
UF=
100;
FQPA
=
1)
0.155
Occupational
and
Residential
NOAEL
mg/
kg/
day
MOE
short
intermediate
&
long­
term
dermal
NA
NA
short­
term
incidental
oral
89
100
Table
1.
Endpoints
Used
for
Piperonyl
Butoxide
Risk
Assessment
Page
6
of
61
short
&
intermediate­
term
inhalation
4
300
long­
term
inhalation
4
1000
Exposure
Assessment
Analysis
of
dietary,
drinking
water,
occupational
and
residential
exposure
pathways
were
included
in
the
piperonyl
butoxide
risk
assessment.
Sources
of
dietary
exposure
include
pre­
and
post
harvest
food
crops,
livestock,
and
food
from
treated
food
processing
facilities
and
food
storage
warehouses.
Drinking
water
exposure
may
occur
due
to
run­
off
from
agricultural
use,
outdoor
pest
control,
mosquito
abatement
and
some
direct
aquatic
uses
(
e.
g.,
carp
bait).
Occupational
exposure
may
occur
through
use
of
piperonyl
butoxide
during
application
for
agricultural,
commercial
and
residential
pest
control,
and
mosquito
abatement
activities.
Residential
exposures
may
occur
through
homeowner
use
of
piperonyl
butoxide
to
control
pests
indoors,
outdoors
and
on
pets.
For
the
occupational
exposures,
short­,
intermediate­,
and
long
term
inhalation
pathways
were
assessed
based
on
label
directed
use
patterns.
For
residential
exposures,
short­
and
intermediate­
term
inhalation
and
incidental
oral
pathways
were
assessed.
Dermal
exposures
were
not
assessed
because
HIARC
concluded
that
no
quantitative
dermal
assessment
is
required
because
no
systemic
effects
were
observed
at
high
doses
in
dermal
toxicity
studies.

Risk
Assessment
and
Risk
Characterization
Risk
assessments
were
conducted
for
dietary,
drinking
water,
residential
and
occupational
exposure
pathways.
An
aggregate
assessment
of
risk
from
the
combined
food
and
drinking
water
pathways
was
also
conducted.
Oral
and
inhalation
residential
exposures
to
piperonyl
butoxide
were
not
aggregated
because
the
toxicity
endpoints
selected
for
these
routes
of
exposure
are
not
common.
A
cumulative
risk
assessment
considering
risks
from
other
pesticides
or
chemical
compounds
having
a
common
mechanism
of
toxicity
has
not
been
conducted
for
this
RED
because
HED
has
not
yet
determined
if
there
are
any
other
chemical
substances
that
have
a
mechanism
of
toxicity
common
with
that
of
piperonyl
butoxide.

Food
Pathway
Exposure
and
Risk
HED
conducted
highly
refined
acute
and
chronic
dietary
exposure
analyses
using
the
Dietary
Exposure
Evaluation
Model
with
the
Food
Commodity
Intake
Database
(
DEEMFCID
 
)
and
the
Lifeline
model.
Dietary
analyses
were
conducted
for
the
general
U.
S.
population
and
all
population
subgroups.

Acute
and
chronic
dietary
risks
are
expressed
as
a
percentage
of
the
acute
or
chronic
Population
Adjusted
Dose
(
aPAD
or
cPAD).
A
dietary
risk
of
100%
of
the
PAD
is
the
target
level
of
exposure
that
should
not
be
exceeded,
(
i.
e.,
estimated
risk
less
than
100%
of
PAD
is
not
of
concern).
The
PAD
is
the
Acute
reference
dose
(
RfD)
or
the
Chronic
RfD
modified
by
the
FQPA
Safety
Factor.
The
safety
factor
for
both
the
acute
and
chronic
dietary
assessments
is
1X.
Page
7
of
61
Based
on
these
analyses,
acute
and
chronic
dietary
risk
from
existing
and
proposed
uses
of
piperonyl
butoxide
are
below
HED's
level
of
concern
for
the
general
US
population
and
population
subgroups.
The
99.9th
percentile
acute
exposure
estimates
were
<
100%
of
the
aPAD.
The
highest
acute
exposures
(
1.2
mg/
kg/
day)
were
in
children
1­
2
years
old
(
20%
aPAD).
Chronic
exposure
estimates
were
also
<
100%
of
the
cPAD,
with
the
highest
chronic
exposure
(
0.02
mg/
kg/
day)
occurring
in
children
1­
2
years
old
(
12%
cPAD).

Drinking
Water
Pathway
Exposure
and
Risk
The
Environmental
Fate
and
Effects
Division
(
EFED)
performed
a
Tier
I
drinking
water
assessment
for
piperonyl
butoxide
in
surface
water
and
groundwater
(
D286223,
W.
Eckel,
5/
17/
04).
EFED
used
the
FIRST
(
FQPA
Index
Reservoir
Screening
Tool)
model
for
estimating
the
upper
bound
on
the
concentrations
that
could
occur
in
surface­
water­
source
drinking
water,
and
SCIGROW
(
Screening
Concentration
in
Ground
Water)
to
estimate
the
concentrations
in
groundwater
used
for
drinking
water.
The
peak
estimated
drinking
water
concentration
(
EDWC)
of
piperonyl
butoxide
in
surface
water
is
240
ppb.
The
annual
average
drinking
water
EDWC
in
surface
water
is
60
ppb.
The
peak
and
annual
average
groundwater
EDWCs
are
0.26
ppb.

Aggregate
Exposures
and
Risks
Since
there
is
potential
for
concurrent
exposure
via
food
and
water,
the
combined
exposures
are
estimated
for
the
aggregate
assessment.
To
assess
aggregate
risk,
drinking
water
levels
of
comparison
(
DWLOCs)
are
compared
with
model­
based
EDWCs
determined
by
EFED.
The
DWLOC
is
a
theoretical
concentration
limit
of
a
chemical
in
drinking
water
that
would
be
acceptable
as
an
upper
limit
in
light
of
total
aggregate
exposure
to
that
chemical
from
food,
water,
and
residential
sources.
Aggregate
risk
for
piperonyl
butoxide
exposure
is
calculated
for
acute
and
long­
term
exposure.
Acute
and
chronic
DWLOCs
include
aggregate
exposure
from
food
and
drinking
water
only.
The
short­
term
DWLOC
aggregates
exposures
from
food,
water
and
residential
routes
associated
with
application
of
piperonyl
butoxide
and
is
calculated
when
there
is
a
common
toxicity
endpoint
for
each
route
of
exposure.

The
acute
DWLOC
is
>
51000
ppb
based
on
the
food
exposure
from
the
most
highly
exposed
subgroup
(
children
1­
2
years).
The
chronic
DWLOC
is
>
1400
ppb
also
based
on
the
food
exposure
for
children
1­
2
years.
The
short
term
DWLOC
for
children
1­
2
years
old
is
8500
ppb.
EFED's
model
based
estimates
for
peak
concentrations
of
piperonyl
butoxide
in
surface
and
ground
water
are
240
and
0.26
ppb
respectively;
estimates
for
average
surface
and
ground
water
concentrations
are
60
and
0.26
ppb
respectively.
Since
the
model­
based
estimates
for
concentrations
in
surface
water
and
groundwater
are
well
below
the
calculated
acute,
short­
term,
and
chronic
DWLOCs,
HED
concludes
that
aggregate
exposure
to
food
and
drinking
water
will
not
result
in
an
unacceptable
risk.

Occupational
and
Residential
Pathway
Exposure
and
Risk
Page
8
of
61
O
O
O
O
CH
3
OC
4
H
9
Occupational
exposure
to
piperonyl
butoxide
can
occur
from
agricultural,
pest
control,
mosquito
abatement
and
veterinary
and
farm
animal
applications.
Thirty­
two
exposure
scenarios
were
identified
and
assessed
as
representative
of
occupational
exposure
for
piperonyl
butoxide
uses.
Post­
application
occupational
exposure
scenarios
are
not
assessed
because
there
is
no
endpoint
for
dermal
exposure,
the
relevant
route
of
exposure
for
post­
application
activities.
Residential
exposure
can
occur
from
indoor
and
outdoor
pest
control
uses
and
pet
application.
Fifteen
residential
handler
and
post­
application
exposure
scenarios
were
assessed.
Short,
intermediate­
and
long­
term
MOEs
were
calculated
for
this
assessment
as
required
based
on
scenario
specific
use/
exposure
patterns.

Exposure
data
used
for
the
piperonyl
butoxide
assessment
are
taken
primarily
from
HED's
Standard
Operating
Procedures
for
residential
and
occupational
exposure.
Risk
estimates
were
conducted
using
maximum
application
rates
from
the
Piperonyl
Butoxide
Master
Label.
A
target
Margin
of
Exposure
(
MOE)
of
300
is
considered
adequate
for
short­
and
intermediate­
term
occupational
and
residential
exposure
via
inhalation
routes.
For
long­
term
occupational
inhalation
exposures,
an
adequate
target
MOE
is
1000.
The
target
MOE
for
residential
incidental
oral
exposures
is
100.
Exposure
estimates
indicate
MOEs
of
concern
(<
the
target
MOE)
at
the
maximum
application
rate
for
ten
of
the
occupational
scenarios
assessed.
The
results
of
the
residential
exposure
assessment
indicate
that,
with
one
exception,
all
of
residential
exposure
scenarios
assessed
result
in
MOEs
greater
than
the
applicable
target
MOEs
and
are
therefore
below
the
level
of
concern.
The
short­
term
residential
bystander
inhalation
from
use
of
piperonyl
butoxide
in
residential
outdoor
automatic
mister
systems
is
the
only
scenario
with
risks
of
concern.
An
assessment
of
residential
exposure
from
use
of
indoor
metered
release
misters
was
not
conducted
due
to
data
limitations.
HED
recommends
that
label
restrictions
provided
in
the
master
label
be
required
for
indoor
automatic
mister
uses.

2.0
PHYSICAL/
CHEMICAL
PROPERTIES
CHARACTERIZATION
The
nomenclature
and
physicochemical
properties
of
piperonyl
butoxide
are
provided
in
Table
2.

TABLE
2.
Piperonyl
Butoxide
Nomenclature
Compound
Chemical
Structure
Common
name
Piperonyl
butoxide
IUPAC
name
5­[
2­(
2­
butoxyethoxy)
ethoxymethyl]­
6­
propyl­
1,3­
benzodioxole
or
2­(
2­
butoxyethoxy)
ethyl
6­
propylpiperonyl
ether
CAS
name
5­[[
2­(
2­
butoxyethoxy)
ethoxy]
methyl]­
6­
propyl­
1,3­
benzodioxole
TABLE
2.
Piperonyl
Butoxide
Nomenclature
Page
9
of
61
CAS
#
51­
03­
6
Physicochemical
Properties
of
the
Technical
Grade
of
Piperonyl
Butoxide
Parameter
Value
Reference
Boiling
point
202­
204
°
C
at
1.9
mm/
Hg
D207185,
1/
27/
99,
T.
Morton
180
°
C
at
1.0
mm/
Hg
2002
Farm
Chemicals
Handbook
Molecular
Weight
338.433
2002
Farm
Chemicals
Handbook
pH
Not
applicable
because
the
TGAI
has
low
solubility
in
water
Density,
bulk
density,
or
specific
gravity
1.059
g/
mL
at
20
°
C
D172854,
11/
30/
92,
A.
Aikens
Water
solubility
14.34
:
g/
mL
at
25
°
C
RD
Memorandum,
12/
31/
90
(
cited
under
D207185,
1/
27/
99,
T.
Morton)

Solvent
solubility
Completely
miscible
(
95%
solution)
in
acetone,
methanol,
petroleum
distillate,
petroleum
ether,
methylene
chloride,
and
isooctane
D207185,
1/
27/
99,
T.
Morton
Vapor
pressure
<
1
x
10­
7
mm
Hg
at
25
°
C
(
extrapolated
from
1.59
x
10­
7
mm
Hg
at
60
°
C
D172854,
11/
30/
92,
A.
Aikens
Dissociation
constant,
pKa
Not
applicable
because
the
TGAI
has
low
solubility
in
water
Octanol/
water
partition
coefficient
4.51
x
104
RD
Memorandum,
12/
31/
90
(
cited
under
D207185,
1/
27/
99,
T.
Morton)

log
Kow
=
4.95
D172854,
11/
30/
92,
A.
Aikens
UV/
visible
absorption
spectrum
Not
available
3.0
HAZARD
CHARACTERIZATION
3.1
Hazard
Profile
The
toxicity
data
base
for
piperonyl
butoxide
is
adequate
for
the
selection
of
doses
and
endpoints
for
use
in
risk
assessment.
HED's
Hazard
Identification
Assessment
Review
Committee
(
HIARC)
evaluated
the
available
studies
and
established
acute
and
chronic
RfDs,
as
well
as
doses
and
endpoints
for
acute,
and
short­,
intermediate­,
and
long­
term
dermal
and
inhalation
exposure
scenarios.
The
Acute
RfD
is
an
estimate
of
a
single
day
oral
exposure
level
for
the
human
population
that
is
likely
to
be
without
an
appreciable
risk
of
deleterious
effects.
The
chronic
RfD
is
an
estimate
of
a
daily
oral
exposure
level
that
is
likely
to
be
without
an
appreciable
risk
of
deleterious
effects
during
a
lifetime.
Acute
and
chronic
RfDs
are
calculated
by
dividing
the
No
Observable
Adverse
Effect
Level
(
NOAEL)
by
the
Uncertainty
Factors
(
UF).
UFs
are
used
to
account
for
differences
between
humans
(
intraspecies
variability)
and
for
differences
between
the
test
animals
and
humans
(
interspecies
extrapolation).
For
occupational
and
residential
exposures,
UFs
are
used
to
determine
adequate
margins
of
exposure
(
MOEs).
The
MOE
is
the
ratio
of
the
route
appropriate
NOAEL
to
the
estimated
exposure.
The
HIARC
also
evaluated
available
studies
to
determine
if
there
was
a
special
sensitivity
for
infants
and
children.
The
toxicological
data
for
piperonyl
butoxide
are
summarized
in
Tables
3
and
4.
Page
10
of
61
3.1.1
Toxicity
Profile
Acute
toxicity
categories
for
piperonyl
butoxide
are
shown
in
Table
3.
Table
4
identifies
guideline
studies
and
open
literature
studies
conducted
for
piperonyl
butoxide
and
summarizes
their
results.

Table
3.
Acute
Toxicity
Data
on
Piperonyl
Butoxide
Study/
Species
MRID
Results
Classification
870.1100
Acute
Oral,
Rats
41969001
LD50
=
4570
mg/
kg
(
m)
7220
mg/
kg
(
f)
Category
IV
(
Under
Review)

870.1200
Acute
Dermal,
Rabbits
41969002
LD50
=
>
2000mg/
kg
Category
IV
(
Under
Review)

870.1300
Acute
Inhalation,
Rats
41990001
LC50
=
>
5.9
mg/
L
Category
IV
870.2400
Primary
Eye
Irritation,
Rabbits
41969004
Minimally
irritating
Category
III
(
Under
Review)

870.2500
Primary
Skin
Irritation,
Rabbits
41969003
Minimally
irritating
Category
III
(
Under
Review)

870.2600
Dermal
Sensitization,
Guinea
pig
41969005
Negative
Category
IV
(
Under
Review)

Table
4.
Piperonyl
Butoxide
Toxicity
Study
Profile
Developmental/
Reproduction
Toxicity
Developmental
Toxicity
Rat
42380801
Doses:
0,
200,
500
and
1000
mg/
kg/
day
Maternal
NOAEL:
200
mg/
kg/
day
Maternal
LOAEL:
500
mg/
kg/
day
Reduction
in
body
weight
gain
and
food
consumption
during
6­
15
days
of
gestation
Developmental
NOAEL:
500
mg/
kg/
day
(
HDT)
Acceptable
Guideline
Developmental
Toxicity
Rabbit
00157157
Doses:
0,
50,
100,
and
200
mg/
kg/
day
Maternal
NOAEL:
200
mg/
kg/
day
(
HDT)
Developmental
NOAEL:
200
mg/
kg/
day
(
HDT)
Acceptable
Guideline
2­
Gen
Reproduction
Study
Rat
00161118
Doses:
0,
300,
1000
and
5000
ppm
0,
27,
89,
469
mg/
kg/
day
(
males)
0,
30,
102,
528
mg/
kg/
day
(
females)
Parental
NOAEL:
89
mg/
kg/
day
Parental
LOAEL:
469
mg/
kg/
day
Decreased
body
weight
gain
Reproductive
NOAEL:
469
mg/
kg/
day
Offspring
NOAEL
89
mg/
kg/
day
Offspring
LOAEL:
469
mg/
kg/
day
(
HDT)
Decreased
body
weight
gain
in
F1
and
F2
pups
Acceptable
Guideline
Table
4.
Piperonyl
Butoxide
Toxicity
Study
Profile
Page
11
of
61
Developmental
Rats
Kennedy
et
al.,
1977
Doses:
0,
300,
1000
mg/
kg/
day
Maternal
NOAEL/
LOAEL:
300/
1000
mg/
kg/
day
Reduction
in
mean
body
weight
gain
during
6­
20
days
of
gestation
Developmental
NOAEL
1000
mg/
kg/
day
(
HDT)
Non­
Guideline
Developmental
Rats
Tanaka
et
al.,
1995
Doses:
0,
630,
1065
or
1800
mg/
kg/
day
Maternal
NOAEL/
LOAEL:
630/
1065
mg/
kg/
day
Reduction
in
bodyweight
gain
(
24­
37%)
during
gestation
Developmental
NOAEL/
LOAEL:
630/
1065
mg/
kg/
day,
Limb
deformities;
HDT
had
increased
resorption
rate
and
decreased
number
of
viable
fetuses
Non­
Guideline
Developmental
Mice
Tanaka
et
al.,
1994
Doses:
0,
1065,
1385,
or
1800
mg/
kg/
day
Maternal
NOAEL:
1800
mg/
kg/
day
(
HDT)
Developmental
NOAEL/
LOAEL:
1065/
1385
mg/
kg/
day:
Early
and
late
fetal
death
and
increased
resorption
rate;
HDT
had
increased
incidence
of
limb
deformities
Non­
Guideline
Reproduction
Single
Generation
Mice
Tanaka,
1992
Doses:
0,1500,
3000,
6000
ppm
Estimated
Dose:
0,
225,
450,
900
mg/
kg/
day
Offspring
NOAEL/
LOAEL:
225/
450
mg/
kg/
day
Decreased
weight
of
the
pups
at
postnatal
days
7
and
14
Neurobehavioral
(
Parental)
NOAEL/
LOAEL:
450/
900
mg/
kg/
day
Decreased
ambulation
and
possibly
rearing
in
F0
male
mice
at
900
mg/
kg/
day
Neurobehavioral
(
Offspring)
NOAEL/
LOAEL:
225/
450
mg/
kg/
day
Decreased
olfactory
orientation
in
F1
mice
Non­
Guideline
Reproduction
Two
Generation,
Mice
Tanaka
et
al.,
1992
Doses:
0,1000,
2000,
4000,
8000
ppm
Chemical
intake:
159,
317,
648,1237
mg/
kg/
day
(
F0);
171,
319,
665,
1341
mg/
kg/
day
(
F1)
NOAEL/
LOAEL
(
Parental):
N/
A
(
No
measurements
made)
NOAEL/
LOAEL
(
Offspring):
319/
665
mg/
kg/
day;
Reduction
in
litter
size
and
litter
weight
in
F2
generation
and
decreased
weight
of
the
F1
and
F2
pups
during
lactation.
Neurobehavioral
NOAEL/
LOAEL
(
Offspring):
171/
319
mg/
kg/
day.
Decreased
olfactory
orientation
in
F2
pups
at
postnatal
day
14
Non­
Guideline
.

Subchronic
Oral
Toxicity
Table
4.
Piperonyl
Butoxide
Toxicity
Study
Profile
Page
12
of
61
Subchronic
(
13
weeks)
Rats
Fujitani
et
al.,
1992
Doses:
0,
6000,
12000,
or
24000
ppm
(
diet)
Estimated
dose
0,
600,
1200,
2400
mg/
kg/
day
NOAEL:
<
600mg/
kg/
day
LOAEL:
600
mg/
kg/
day
based
on
36­
39
%
increase
in
relative
liver
weight
and
133­
150%
increase
in
gamma
glutamyl
transpeptidase
Non­
Guideline
Subchronic
(
12
weeks)
Rats
Fujitani
et
al.,
1993a
Doses:
0,
6000,
12000,
or
24000
ppm
(
diet)
Estimated
dose
0,
600,
1200,
2400
mg/
kg/
day
NOAEL:
<
600mg/
kg/
day
LOAEL:
600
mg/
kg/
day
based
on
increases
in
relative
liver
weight
and
in
gamma
glutamyl
transpeptidase
Non­
Guideline
Subchronic
(
20
days)
Mice
Fujitani
et
al.,
1993b
Doses:
0,1000,
3000
or
9000
ppm
(
diet)
Estimated
dose
0,
150,
450,
1350
mg/
kg/
day
NOAEL/
LOAEL:
150/
450
mg/
kg/
day
based
on
increased
cholesterol,
gamma
glutamyl
transpeptidase
and
liver
weights
Non­
Guideline
Subchronic
(
6
weeks)
Mice
Tanaka,
1993
Doses:
0,
1500,
3000
and
6000
ppm
Equivalent
to
0,
236,
448
and
880
mg/
kg/
day
Neurobehavioral
NOAEL:<
236
mg/
kg/
day
LOAEL:
236
mg/
kg/
day
based
on
effects
on
motor
activity­
i.
e.,
increased
number
of
turnings
and
total
distance
traveled
per
10
minutes
Non­
Guideline
Chronic
Oral
Toxicity
870.4100
Chronic
Toxicity
­
Dogs
42926001,
42926002
Doses:
0,
100,
600
or
2000ppm
0,
2.9,
15.5,
52.8
mg/
kg/
day
(
males),
0,
2.8,
16.3,
or
71.0
mg/
kg/
day
(
females)
NOAEL:
15.5
mg/
kg/
day
LOAEL:
52.8
mg/
kg/
day
­
Decreased
body
weight
gain,
increased
in
alkaline
phosphatase
and
relative
liver
weights
and
hepatocellular
hypertrophy
(
75­
100%
animals)
Acceptable­
Guideline
Combined
Chronic
Carcinogenicity
870.4300
Combined
chronic
toxicity/
carcinogenicity
Rats
40323701
Doses:
0,30,
100
or
500
mg/
kg/
day
NOAEL:
30
mg/
kg/
day
LOAEL:
100
mg/
kg/
day
­
increased
liver
weight,
increased
cholesterol
levels,
gross
and
histopathological
liver
effects
Negative
for
liver
tumors
Note:
Butler
et
al.,
1998
confirmed
the
negative
tumor
effects
after
reevaluation
of
pathological
findings
Acceptable/
Guideline
Table
4.
Piperonyl
Butoxide
Toxicity
Study
Profile
Page
13
of
61
870.4300
Combined
chronic
toxicity/
carcinogenicity
Rats
42839601,
42920201
Doses:
0,
547,
1052,
1877
mg/
kg/
day
(
males)
0,
537,
1061,
and
2002
mg/
kg/
day
(
females)
NOAEL:
<
537
mg/
kg/
day
LOAEL:
537
mg/
kg/
day
­
Decreased
body
weight
gain,
increased
liver
weights,
effect
on
RBC
parameters
(
abnormal
shaped
erythrocytes),
enlargement
and
hemorrhage
effects
in
cecum
Hepatocellular
adenoma
and
carcinomas
in
both
sexes
Acceptable/
Non­
Guideline
870.4300
Combined
chronic
toxicity/
carcinogenicity
Mice
42903701,
42978001
Doses:
0,
30,
100
or
300
mg/
kg/
day
NOAEL:
30
mg/
kg/
day
LOAEL:
100
mg/
kg/
day
­
Increased
liver
weight
relative
to
body
weight,
and
liver
hypertrophy
Hepatocellular
adenomas
and
carcinomas
in
males
and
hepatocellular
adenomas
alone
in
females
Note:
Butler
et
al.,
1998
confirmed
the
negative
tumor
effects
after
reevaluation
of
pathological
findings
Acceptable/
Guideline
2­
year
Carcinogenicity
Rats
NTP,
1979
Doses:
0,
5000
and
10,000
ppm
(
diet)
Negative
for
tumor
effects
Non­
Guideline
2­
year
Carcinogenicity
Rats
Maekawa
et
al.,
1985
Doses:
0,
5000
and
10,000
ppm
(
diet)
Estimated
Chemical
Intake:
0,
500
and
1000
mg/
kg/
day
Negative
for
tumor
effects
Non­
Guideline
1­
year
Carcinogenicity
Mice
Takahashi
et
al.,
1994
Doses:
0,
6000
and
12,000
ppm
(
diet)
Dose
dependent
increase
in
hepatocellular
adenomas
and
carcinomas;
Hemangioendothelial
sarcomas
in
males
Takahashi
et
al.,
1997reported
similar
findings
in
females.
Non­
Guideline
11/
2
­
year
Carcinogenicity
Mice
NTP,
1979
Doses:
0,
6000
and
12,000
ppm
(
diet)
Negative
for
tumor
effects
Non­
Guideline
Subchronic
Dermal/
Inhalation
Toxicity
21­
Day
Dermal
Toxicity
Rabbit
42218201
Doses:
0,
100,
300
and
1000
mg/
kg/
day
Systemic
NOAEL:
$
1000
mg/
kg/
day
(
HDT)
Dermal
LOAEL:
100
mg/
kg/
day
(
LDT)
mild
irritant
,
Very
slight
erythema,
edema
and
desquamation
and
histpathological
effects
such
as
acanthosis,
hyperkeratosis
and
chronic
inflammation
of
the
epidermis
Acceptable/
Guideline
Table
4.
Piperonyl
Butoxide
Toxicity
Study
Profile
Page
14
of
61
90­
day
Inhalation
Toxicity
Rat
42477101
Doses:
0,
0.015,
0.074,
0.155
and
0.512
mg/
L
Systemic
NOAEL:
0.155
mg/
L
Systemic
LOAEL:
0.512
mg/
L
increased
liver
and
kidney
weights
Respiratory
NOAEL
­
Not
Established
Respiratory
LOAEL­
0.015
mg/
L
(
LDT)
metaplasia/
hyperplasia
in
the
larynx
Acceptable/
Guideline
Metabolism
Rat
Metabolism
41998701
41998401
Most
of
the
administered
radioactivity
was
found
in
feces
and
urine
in
48
hours
after
single
oral
dose
of
50
or
500
mg/
kg
bw.
Less
than
1.5%
of
the
administered
radioactivity
was
present
in
tissues
after
168
hours.
The
highest
levels
were
in
the
small
intestine
and
liver.
Acceptable
Guideline
Rat
Metabolism
45582701
The
dose
administration
was
similar
to
the
metabolism
study
above.
PBO
was
excreted
mainly
in
0­
48
hour
urine
and
feces
and
less
than
0.5%
identified
in
tissues
at
168
hours.
Major
metabolite
in
feces
was
identified
as
M3
i.
e.,
PBO
opened
at
the
methylene
dioxy
ring
(
approximately
20%
of
the
radioactivity).
Urine
contained
several
radioactive
peaks
(~
20
peaks)
and
none
of
these
individual
peaks
exceeded
5%
of
the
administered
radioactivity.
The
urine
metabolites
are
found
conjugated
with
sulfate
or
glucuronide
subsequent
to
oxidation
of
PBO
in
the
methylenedioxy
ring
and/
or
2­(
2­
butoxyethoxy)
ethoxymethyl
side
chain.
Acceptable
Guideline
Mutation/
Genotoxicity
870.5100
Bacterial
Reverse
Mutation
Assay
42004502
No
evidence
of
mutagenicity
in
Salmonella
typhimurium
strains
TA1535,
TA1537,
TA1538,
TA98
or
TA100
in
the
presence
or
absence
of
metabolic
activation
Doses
100­
5000
:
g/
plate
Acceptable
Guideline
870.5100
Bacterial
Reverse
Mutation
Assay
NTP
00143499
No
evidence
of
gene
mutations
in
Salmonella
typhimurium
(
TA
1535,
TA1537,
TA98,
TA100)
with
and
without
metabolic
activation.
Dose
up
to
10
mg/
plate
Acceptable
Guideline
870.5300
In
vitro
Mammalian
Cell
Gene
Mutation
Assay
00147693
Equivocal
response
in
75
:
g/
ml
only
under
nonactivated
conditions
in
CHO
cells.
Doses10­
100
:
g/
ml
(
without
activation)
Doses
25­
500
:
g/
ml
(
with
activation)
Acceptable
Guideline
Table
4.
Piperonyl
Butoxide
Toxicity
Study
Profile
Page
15
of
61
870.5375
In
vitro
Mammalian
Cell
Chromosomal
Aberrations
Test
43013801
No
induction
of
chromosomal
aberration
in
CHO
cells
Doses
in
non
activated
condition:
15.0­
30.0
:
g/
mL
for
10
or
20
hours
Doses
in
S9activated
condition:
12­
120
:
g/
mL
for
2,
10,
20
or
30
hours
Acceptable
Guideline
870.5375
In
vitro
Mammalian
Cell
Chromosomal
Aberrations
Test
NTP
00143499
No
evidence
of
induction
of
chromosomal
aberrations
in
CHO
cells
Acceptable
Guideline
870.5550
Unscheduled
DNA
Synthesis
in
Rat
Primary
Hepatocytes
42004503
No
evidence
of
induction
of
unscheduled
DNA
synthesis
Dose
Levels
tested:
5,10,
25
and
50
:
g/
ml
Cytotoxic
at
$
74.9
:
g/
ml
Acceptable
Guideline
870.5900
In
vitro
Sister
Chromatid
Exchange
Assay
NTP
00143499
The
study
does
not
indicate
sister
chromatid
exchanges
in
CHO
cells
with
and
without
metabolic
activation.
Acceptable
Guideline
Microsomal
Enzyme
Inhibition/
Others
In
vitro
study
Liver
microsomes
Rats,
Rabbits,
Mice
Franklin,
1972
Inhibition
of
ethylmorphine
N­
demethylation
by
PBO
is
proportional
to
amount
of
Cytochrome
P­
450
and
PBO
metabolite
complex
Non­
Guideline
Regulation
of
cytochrome
P450
enzymes
Mice
Adams
et
al.,
1993
Single
i.
p.
dose
at
0,
52,
104,
156,
208
or
400
mg
PBO/
kg
bw
Induction
of
cytochrome
P450
1a1mRNA,
protein
and
enzyme
activity
at
doses
$
104
mg/
kg
at
24
hours
Non­
Guideline
Regulation
of
cytochrome
P450
enzymes
Mice
Ryu
et
al.,
1997
Single
i.
p.
dose
at
0,
400
mg
PBO/
kg
bw
Induction
of
cytochrome
P450
1a1and
1a2
mRNAs
at
24
hours
in
liver
by
PBO
treatment.
Non­
Guideline
WHO
Report
JMPR,
1995
PBO
Toxicological
Evaluation
N/
A
3.1.2
Hazard
Characterization
Piperonyl
butoxide
has
a
low
acute
toxicity
by
oral,
inhalation
and
dermal
routes.
It
has
been
assigned
toxicity
Category
IV
by
all
exposure
routes.
In
the
acute
studies,
piperonyl
butoxide
has
been
identified
as
minimally
irritating
to
eyes
and
skin.
In
the
subchronic
dermal
study
using
rabbits,
piperonyl
butoxide
is
classified
as
a
mild
irritant.
The
dermal
lesions
include
gross
effects
such
as
very
slight
erythema,
edema
and
desquamation
(
30%
of
the
animals)
and
histopathological
effects
such
as
acanthosis,
hyperkerartosis
and
chronic
inflammation
of
epidermis.
Piperonyl
butoxide
is
reported
negative
for
dermal
sensitization
effects.
In
a
Page
16
of
61
subchronic
inhalation
toxicity
study,
mild
hyperplasia
and
metaplasia
were
noticed
in
the
respiratory
tract
of
rats
The
major
target
organ
for
piperonyl
butoxide
induced
toxicity
is
the
liver.
Subchronic
studies
in
rats
showed
piperonyl
butoxide
treatment
caused
increases
in
liver
weight,
and
in
clinical
parameters
such
as
cholesterol
and
gamma
glutamyl
transpeptidase
activity
compared
to
controls.
Liver
histopathological
effects
such
as
enlargement
of
hepatocytes
with
glassy
cytoplasm,
oval
cell
proliferation,
bile
duct
hyperplasia,
and
focal
necrosis
were
observed
in
treated
rats.
In
ICR
mice,
similar
effects
(
increased
liver
weight,
cholesterol
and
gamma
glutamyl
transpeptidase
activity
as
well
as
liver
histolopathological
effects)
occurred
after
20
days
of
treatment.
One
year
treatment
of
dogs
with
piperonyl
butoxide
also
resulted
in
pronounced
liver
effects
such
as
increased
liver
weight,
hepatocyte
hypertrophy
and
elevated
serum
alkaline
phosphatase
activity.

In
combined
chronic/
carcinogenic
oral
toxicity
studies,
liver
tumorigenic
effects
were
reported
in
rats
only
when
tested
at
excessive
doses.
In
Fisher
344
rats
increases
in
liver
adenomas
and
carcinomas
were
reported
in
both
sexes
of
the
rats
at
doses
close
to
or
higher
than
the
limit
dose.
At
these
doses,
hemorrhage
effects
in
the
stomach
and
cecum
were
also
noticed.
No
liver
tumor
effects
were
reported
in
Sprague
Dawley
rats
when
tested
at
half
limit
dose.
Maekawa
et
al.
also
reported
negative
carcinogenic
effects
in
F344/
DuCrj
rats
even
at
doses
where
high
incidence
of
ileocaecal
ulcers
were
noticed.
A
1979
NTP
study
also
reported
negative
effects
for
carcinogenicity
in
same
strain
of
rats.
In
chronic
oral
toxicity
studies
using
CD­
1
mice,
statistically
significant
increases
in
hepatocellular
adenomas,
carcinomas
and
combined
adenomas/
carcinomas
in
males
and
adenomas
alone
in
females
(
all
at
p<
0.01)
were
reported.
The
non­
guideline
studies
also
reported
increased
incidences
of
hepatocellular
adenomas
and
carcinomas
and
hemangioendothelial
sarcoma
in
CD­
1
mice
treated
with
piperonyl
butoxide.
The
NTP
study
reported
negative
effects
for
carcinogenicity
in
B6C3F1
mice.
Piperonyl
butoxide
is
classified
as
a
Group
C
­
possible
human
carcinogen.
No
cancer
quantification
is
required
for
piperonyl
butoxide
uses.

No
developmental
toxic
effects
were
noted
in
guideline
studies
using
rats
and
rabbits.
A
few
developmental
studies
in
the
open
literature
reported
limb
deformities,
increased
resorption
and
decreased
number
of
viable
fetuses
in
rodents
at
doses
close
to
or
higher
than
the
limit
dose.
Neurotoxic
effects
of
piperonyl
butoxide
are
not
evident
from
the
clinical
signs
reported
in
developmental,
reproductive
and
chronic
studies
submitted
to
the
Agency.

Piperonyl
butoxide
tested
negative
in
bacterial
gene
mutation
assays.
The
in
vitro
mammalian
cell
mutation
assays
indicate
a
questionable
positive
effect
for
mutation.
Piperonyl
butoxide
tested
negative
for
chromosomal
aberration
and
sister
chromatid
exchange
in
CHO
cells
and
no
induction
of
unscheduled
DNA
synthesis
was
observed
in
rat
primary
hepatocytes.

The
main
route
of
phenyl
labeled
piperonyl
butoxide
excretion
in
rats
occurs
via
urine
and
feces.
The
amount
of
administered
labeled
radioactivity
was
found
at
64­
85%
in
feces,
11­
30%
in
Page
17
of
61
urine
and
below
0.5%
in
tissues.
The
majority
of
the
administered
radioactivity
was
excreted
in
0­
48
hour
urine
and
feces.
The
parent
and
the
M3
metabolite
i.
e.,
piperonyl
butoxide
opened
at
the
methylene
dioxy
ring
were
the
major
compounds
identified
in
feces
(
approximately
20%
of
the
radioactivity
for
each).
Several
radioactive
peaks
(~
20
peaks)
were
observed
in
urine
samples
and
none
of
these
individual
peaks
exceeded
5%
of
the
administered
radioactivity.
The
metabolites
in
the
urine
are
polar
and
are
found
conjugated
with
sulfate
or
glucuronide
subsequent
to
oxidation
of
piperonyl
butoxide
in
the
methylenedioxy
ring
and/
or
2­(
2­
butoxyethoxy)
ethoxymethyl
side
chain.

Piperonyl
butoxide
is
well
known
to
inhibit
microsomal
enzymes
in
insects
by
direct
binding
to
these
enzymes
and
inhibit
the
breakdown
of
other
insecticides
such
as
pyrethrins
and
pyrethroids.
It
also
inhibits
the
microsomal
enzymes
in
several
other
species
(
e.
g.,
rats,
rabbits,
mice).
The
concentrations
at
which
piperonyl
butoxide
binds
to
the
enzyme
and
the
affinity
of
binding
to
the
enzyme
and
the
stability
of
the
cytochrome
P450­
piperonyl
butoxide
metabolite
complex
are
some
major
factors
that
determine
the
potency
of
inhibition
among
different
species.

Piperonyl
butoxide
is
used
as
a
classical
compound
in
several
pharmacological
experiments
to
compare
the
therapeutical
or
toxicological
effects
of
several
drugs
before
or
after
metabolism
in
rodents.
Although
piperonyl
butoxide
is
reported
to
inhibit
the
microsomal
enzymes
in
mammalian
system,
it
is
shown
to
exhibit
biphasic
effects,
i.
e.,
initial
inhibition
followed
by
stimulation
of
microsomal
enzymes
upon
continued
exposure.
Evidence
from
the
published
literature
indicates
that
piperonyl
butoxide
is
administered
as
a
single
dose
at
$
100
mg/
kg
bw
in
rats
and
mice
(
with
the
exception
of
5­
25
mg/
kg
bw
in
a
couple
of
mice
studies)
to
inhibit
microsomal
enzymes.
Evidence
suggests
that
the
inhibition
of
microsomal
enzymes
is
a
transient
effect
in
these
drug
interaction
studies.
As
early
as
24
hours
after
the
dosing,
the
increase
in
microsomal
enzymes
are
observed
at
the
activity
level
as
well
as
at
mRNA
and
protein
levels.
The
kinetics
of
the
inhibition
and/
or
stimulation
and
the
influence
on
the
specificity
of
the
microsomal
enzymes
affected
upon
exposure
to
piperonyl
butoxide
are
not
established
in
humans.

3.2
FQPA
Considerations
HIARC
determined
that
the
special
FQPA
safety
factor
should
be
reduced
from
10x
to
1x
due
to
low
degree
of
concern
for
the
fetal
susceptibility
effects
and
no
evidence
of
residual
uncertainties
for
pre­
and
postnatal
toxicity.
The
FQPA
safety
factor
recommended
by
the
HIARC
assumes
that
the
exposure
databases
(
dietary
food,
drinking
water,
and
residential)
are
complete
and
that
the
risk
assessment
for
each
potential
exposure
scenario
includes
all
metabolites
and/
or
degradates
of
concern
and
does
not
underestimate
the
potential
risk
for
infants
and
children.

There
are
no
residual
uncertainties
identified
in
the
exposure
databases
relevant
to
potential
exposure
to
infants
and
children.
The
highly
refined
dietary
food
exposure
assessment
uses
residue
data
from
the
USDA
Pesticide
Data
Program,
actual
percent
crop
treated
data
from
BEAD
where
available,
and
processing
factors
from
processing
study
data.
The
drinking
water
Page
18
of
61
assessment
utilizes
water
concentration
values
generated
by
model
and
associated
modeling
parameters
which
are
designed
to
provide
health
protective,
high­
end
estimates
of
water
concentrations
which
will
not
likely
be
exceeded.
Use
of
piperonyl
butoxide
specific
dietary
food
exposure
data
is
intended
to
enhance
the
accuracy
of
the
assessment
but
will
not
result
in
an
underestimation
of
actual
exposures/
risks.
Therefore,
these
assessments
will
not
underestimate
the
potential
exposure
to
infants
and
children
resulting
from
the
use
of
piperonyl
butoxide.

3.3
Dose
Response
Assessment
Doses
and
toxicological
endpoints
selected
for
various
exposure
scenarios
are
summarized
in
Table
5.

Table
5.
Endpoints
selected
by
HIARC
for
Assessing
Occupational
and
Residential
Risks
for
Piperonyl
Butoxide
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
General
Population
NOAEL=
630
mg/
kg/
day
UF
=
100
Acute
RfD
=
6.3
mg/
kg/
day
FQPA
SF
=
1X
aPAD
=
acute
RfD
FQPA
SF
=
6.3
mg/
kg/
day
Developmental
toxicity
study,
rats
(
Tanaka
et
al.,
1995)

LOAEL
=
1065
mg/
kg/
day
based
on
decrease
in
maternal
body
weight
gain
Acute
Dietary
Females
13­
49
years
N/
A
N/
A
Acute
Dietary
Endpoint
for
General
Population
is
considered
protective
for
this
population.
No
separate
endpoint
is
selected.

Chronic
Dietary
(
All
populations)
NOAEL=
15.5
mg/
kg/
day
UF
=
100
Chronic
RfD
=
0.16
mg/
kg/
day
FQPA
SF
=
1X
cPAD
=
chronic
RfD
FQPA
SF
=
0.16
mg/
kg/
day
Chronic
oral
toxicity
study,
dogs
LOAEL
=
52.8
mg/
kg/
day
based
on
decrease
in
body
weight
gain,
and
increases
in
alkaline
phosphatase
activity,
liver
weight
and
hepatocellular
hypertrophy
Short­
Term
Incidental
Oral
(
1­
30
days)
NOAEL=
89
mg/
kg/
day
Residential
MOE
=
100
Occupational
MOE
=
100
Two
generation
reproduction
study,
rats
LOAEL
=
469
mg/
kg/
day
based
on
the
decrease
in
body
weight
gain
of
F1
and
F2
pups
at
postnatal
day
21
Intermediate­
Term
Incidental
Oral
(
1­
6
months)
NOAEL=
89
mg/
kg/
day
Residential
MOE
=
100
Occupational
MOE
=
100
Two
generation
reproduction
study,
rats
LOAEL
=
469
mg/
kg/
day
based
on
the
decrease
in
body
weight
gain
of
F1
and
F2
pups
at
postnatal
day
21
Short­
Term
Dermal
(
1
to
30
days);
Intermediate­
Term
Dermal
(
1
to
6
months);
Long­
Term
Dermal
(>
6
months)
N/
A
N/
A
No
systemic,
developmental
and
neurotoxicity
concerns
at
the
limit
dose.
Therefore,
no
quantification
is
required.
PBO
is
classified
as
mild
irritant.
Contact
should
be
avoided.
Table
5.
Endpoints
selected
by
HIARC
for
Assessing
Occupational
and
Residential
Risks
for
Piperonyl
Butoxide
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Page
19
of
61
Acute
Inhalation
(<
2
hrs)
(
inhalation
absorption
rate
=
100
%)
NOAEL=
630
mg/
kg/
day
Residential
MOE
=
100
Developmental
toxicity
study,
rats
(
Tanaka
et
al.,
1995a)
LOAEL
=
1065
mg/
kg/
day
based
on
decrease
in
maternal
body
weight
gain
Short­
Term
Inhalation
(
1
to
30
days)
Respiratory
LOAEL=
3.91
mg/
kg/
day
(
0.015
mg/
L)
Residential
MOE
=
300
Occupational
MOE
=
300
Subchronic
inhalation
toxicity
study,
rats
Respiratory
LOAEL
=
3.91
mg/
kg/
day
(
0.015
mg/
L)
based
on
laryngeal
hyperplasia
and
metaplasia
Intermediate­
Term
Inhalation
(
1
to
6
months)
Respiratory
LOAEL=
3.91
mg/
kg/
day
(
0.015
mg/
L)
Residential
MOE
=
300
Occupational
MOE
=
300
Subchronic
inhalation
toxicity
study,
rats
Respiratory
LOAEL
=
3.91
mg/
kg/
day
(
0.015
mg/
L)
based
on
laryngeal
hyperplasia
and
metaplasia
Long­
Term
Inhalation
(>
6
months)
Respiratory
LOAEL=
3.91
mg/
kg/
day
(
0.015
mg/
L)
Residential
MOE
=
1000
Occupational
MOE
=
1000
Subchronic
inhalation
toxicity
study,
rats
Respiratory
LOAEL
=
3.91
mg/
kg/
day
(
0.015
mg/
L)
based
on
laryngeal
hyperplasia
and
metaplasia
Cancer
NA
NA
Classified
as
"
Group
C
carcinogen"
with
no
quantification
3.3.1
Dietary
Exposure
Endpoints
3.3.1.1
Acute
Reference
Dose
For
acute
dietary
general
population
exposure,
an
oral
NOAEL
of
630
was
selected
from
a
rat
developmental
study
based
on
maternal
decrease
in
body
weight
gain
during
gestation
at
the
LOAEL
of
1065
mg/
kg/
day.
Although
the
study
reported
the
body
weight
changes
after
two
gavage
doses
during
gestation
days
11­
12,
it
is
reasonable
to
assume
that
effects
could
have
occurred
after
a
single
dose
administration
and
thus
are
considered
appropriate
for
acute
RfD
selection.
The
HIARC
recommended
a
UF
of
100x
(
10x
for
interspecies
and
10x
for
intraspecies
is
extrapolation)
which
results
in
an
RfD
of
6.3
mg/
kg/
day.
No
separate
endpoint
was
selected
for
the
subpopulation
of
females,
ages
13­
49
years,
because
the
study
selected
for
the
general
population
is
considered
protective
for
this
subpopulation.

3.3.1.2
Chronic
Reference
Dose
Acute
RfD
(
General
population)
=
630
mg/
kg/
day
(
NOAEL)
=
6.3
mg/
kg/
day
100
(
UF)
Page
20
of
61
For
chronic
dietary
exposure
for
all
populations,
the
toxicology
endpoint
was
selected
from
a
chronic
oral
toxicity
study
in
dogs
in
which
the
NOAEL
was
15.5
mg/
kg/
day
and
the
LOAEL
was
52.8
mg/
kg/
day,
based
on
decreases
in
body
weight
gain,
increased
alkaline
phosphatase
activity
and
increased
liver
weight
and
hepatocellular
hypertrophy.
This
study
was
selected
because;
1)
dogs
appear
to
be
the
more
sensitive
species
for
the
toxic
effects
of
piperonyl
butoxide
than
rats
and
mice,
2)
it
is
appropriate
for
the
duration
and
route
of
exposure,
3)
it
has
endpoints
similar
to
those
reported
in
other
chronic
studies
such
as
combined
chronic
and
carcinogenicity
studies
in
mice
and
rats
4)
there
are
no
developmental
and
reproductive
concerns
at
the
doses
selected
for
risk
assessment,
and
5)
it
was
also
used
for
deriving
the
Acceptable
Daily
Intake
(
ADI)
of
piperonyl
butoxide
by
the
Joint
FAO/
WHO
Meeting
on
Pesticide
Residues
in
1995.
The
HIARC
recommended
application
of
a
conventional
UF
of
100
resulting
in
a
chronic
RfD
of
0.155
mg/
kg/
day.

3.3.2
Occupational
and
Residential
Exposure
Endpoints
3.3.2.1
Dermal
Exposure
No
dose
or
endpoints
were
selected
for
dermal
exposure.
HIARC
concluded
that
no
quantitative
dermal
assessment
is
required
because
no
systemic
effects
were
observed
at
the
limit
dose
in
the
21­
day
dermal
toxicity
study
in
rabbits.
In
the
21­
day
rabbit
dermal
toxicity
study,
dose
levels
of
1000
mg/
kg/
day
produced
no
treatment
related
effect
on
mortality
rate,
food
consumption,
body
weight
gain,
hematology,
clinical
chemistry,
absolute/
relative
organ
weights,
and
histopathology.
However,
piperonyl
butoxide
was
observed
to
be
a
mild
irritant
i.
e.,
macro
and
micropathology
of
the
tested
sites
exhibited
dermal
lesions
associated
with
irritation.
The
dermal
lesions
include
gross
effects
such
as
very
slight
erythema,
edema
and
desquamation
(
30%
of
the
animals)
and
histopathological
effects
such
as
acanthosis,
hyperkeratosis
and
chronic
inflammation
of
epidermis.

3.3.2.2
Dermal
Absorption
Since
no
dermal
endpoint
was
selected,
a
dermal
absorption
factor
is
not
needed.

3.3.2.3
Inhalation
Exposure
Acute­,
Short­,
Intermediate­,
and
Long­
Term
For
acute
inhalation
exposure
(
e.
g.,
<
2
hours)
the
toxicology
endpoint
was
selected
from
a
rat
developmental
study
in
which
the
oral
NOAEL
was
630
mg/
kg/
day
based
on
maternal
decrease
in
body
weight
gain
during
gestation
at
the
LOAEL
of
1065
mg/
kg/
day.
In
the
absence
of
appropriate
acute
inhalation
toxicity
studies,
the
default
value
of
100%
for
inhalation
Chronic
RfD
=
15.5
mg/
kg/
day
(
NOAEL)
=
0.155
mg/
kg/
day
100
(
UF)
Page
21
of
61
absorption
was
used
for
route­
to­
route
extrapolations.
The
target
margin
of
exposure
(
MOE)
for
acute
inhalation
exposures
to
piperonyl
butoxide
is
100
based
on
the
conventional
uncertainty
factor
of
100X.

For
short­,
intermediate­
and
long­
term
inhalation
exposures,
the
toxicology
endpoint
was
selected
from
a
subchronic
inhalation
toxicity
study
in
rats
in
which
the
LOAEL
was
3.91
mg/
kg/
day
based
on
the
laryngeal
hyperplasia
and
metaplasia.
A
respiratory
NOAEL
was
not
established
because
lesions
in
the
larynx
were
present
in
all
treated
groups.
The
selected
endpoint
is
considered
appropriate
for
assessing
all
durations
of
inhalation
exposure
based
on
route
and
duration
of
the
study.

A
target
MOE
of
300
was
determined
by
HIARC
to
be
adequate
for
short
and
intermediate
term
inhalation
exposures
to
piperonyl
butoxide.
The
short­
and
intermediate­
term
target
MOE
includes
the
conventional
uncertainty
factor
of
100X
and
an
additional
3X
uncertainty
factor
for
the
use
of
a
LOAEL.
For
long
term
exposures,
HIARC
recommended
a
target
of
1000.
HIARC
recommended
that
the
long­
term
target
MOE
be
increased
to
1000
to
account
for
lesions
in
the
respiratory
tract
that
might
progress
into
long
term
adverse
effects
(
e.
g.,
cancer).

3.3.2.4
Incidental
Oral
Exposure
­
Short­
and
Intermediate­
Term
For
short­
and
intermediate­
term
incidental
oral
exposure,
an
oral
NOAEL
of
89
mg/
kg/
day
was
selected
from
a
two
generation
reproduction
study
in
rats
based
on
the
decrease
in
body
weight
gain
of
F
1
and
F
2
pups
at
postnatal
day
21
at
the
LOAEL
of
469
mg/
kg/
day.
Since
the
pup
weights
are
affected
significantly
during
lactation
phase
at
postnatal
day
21,
and
there
is
a
trend
for
decrease
in
pup
weight
at
postnatal
day
4,
the
endpoints
selected
are
considered
appropriate
for
assessing
risks
to
infants
and
children
from
this
exposure
scenario.
A
target
MOE
of
100
was
selected
as
adequate
for
incidental
oral
exposures
based
on
the
conventional
uncertainty
factor
of
100X.

3.3.2.5
Common
Toxicological
Endpoints
for
Aggregate
Exposure
&
Risk
When
there
are
potential
residential
exposures
to
the
pesticide,
aggregate
risk
assessment
must
consider
exposures
from
oral,
dermal
and
inhalation
exposures.
The
toxicity
endpoints
selected
for
these
routes
of
exposure
may
be
aggregated
if
there
are
common
toxicity
endpoints
(
clinical
signs)
via
these
routes.
However,
since
the
toxicity
endpoints
selected
for
oral
and
inhalation
routes
of
exposure
are
not
common,
the
risk
may
not
be
aggregated
for
piperonyl
butoxide
uses.

3.4
Endocrine
Disruptor
Effects
EPA
is
required
under
the
FFDCA,
as
amended
by
FQPA,
to
develop
a
screening
program
to
determine
whether
certain
substances
(
including
all
pesticide
active
and
other
ingredients)
"
may
Page
22
of
61
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
other
such
endocrine
effects
as
the
Administrator
may
designate."
Following
recommendations
of
its
Endocrine
Disruptor
and
Testing
Advisory
Committee
(
EDSTAC),
EPA
determined
that
there
was
a
scientific
basis
for
including,
as
part
of
the
program,
the
androgen
and
thyroid
hormone
systems,
in
addition
to
the
estrogen
hormone
system.
EPA
also
adopted
EDSTAC's
recommendation
that
the
Program
include
evaluations
of
potential
effects
in
wildlife.
For
pesticide
chemicals,
EPA
will
use
FIFRA
and,
to
the
extent
that
effects
in
wildlife
may
help
determine
whether
a
substance
may
have
an
effect
in
humans,
FFDCA
authority
to
require
the
wildlife
evaluations.
As
the
science
develops
and
resources
allow,
screening
of
additional
hormone
systems
may
be
added
to
the
Endocrine
Disruptor
Screening
Program
(
EDSP).
In
the
available
toxicity
studies
on
piperonyl
butoxide,
there
was
no
toxicologically
significant
evidence
of
endocrine
disruptor
effects.

When
additional
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
EDSP
have
been
developed,
piperonyl
butoxide
may
be
subjected
to
further
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.

4.0
DIETARY
AND
DRINKING
WATER
EXPOSURE/
RISK
ASSESSMENT
4.1
Summary
of
Registered
Uses
The
food/
feed
uses
of
piperonyl
butoxide
which
are
being
supported
by
the
Piperonyl
Butoxide
Task
Force
II
for
reregistration
include;
preharvest
and
postharvest
uses
on
agricultural
crops,
direct
and
indirect
treatments
of
livestock
animals
and
premises,
treatments
of
commercial
and
industrial
facilities
and
storage
areas
where
raw
and
processed
food/
feed
commodities
are
stored
or
processed,
and
mosquito
abatement
on
agricultural
fields,
including
aquatic
areas.
BEAD
provided
a
screening
estimate
of
usage
based
on
1997
­
2001
data
from
OPP's
principal
agricultural
pesticide
usage
databases.
Based
on
BEAD's
estimates
the
highest
usage
of
piperonyl
butoxide
is
on
potatoes
(
30%
crop
treated)
with
all
other
uses
at
5%
or
less.
Page
23
of
61
4.2
Dietary
Exposure/
Risk
Pathway
4.2.1
Residue
Profile
4.2.1.1
Nature
of
the
Residue
­
Plants
and
Livestock
Plants
The
registrants
have
submitted
acceptable
plant
metabolism
studies
on
lettuce,
cotton,
and
potatoes.
The
nature
of
the
residue
in
plants
is
adequately
understood.
The
HED
Metabolism
Assessment
Review
Committee
(
MARC)
concluded
the
terminal
residues
of
concern
in
plants
(
i.
e.,
residues
that
need
to
be
regulated
or
included
in
the
tolerance
expression)
is
piperonyl
butoxide
per
se)
(
T.
Morton,
D304469,
6/
30/
04).
Metabolism
studies
conducted
on
lettuce,
cotton,
and
potato
indicated
that
parent
is
the
only
major
residue
(>
10%
total
radioactive
residue
(
TRR)).
However,
all
the
plant
metabolism
studies
are
poorly
conducted
in
that
only
20
­
40
%
of
the
TRR
were
successfully
identified.
Only
the
lettuce
study
firmly
identified
any
metabolites.
The
latter
represented
conjugates
in
which
the
polyether
side
chain
had
been
hydroxylated
or
cleaved
at
one
of
the
ether
linkages.
These
conjugates
are
similar
to
some
metabolites
observed
in
the
rat.
MARC
does
not
believe
that
these
metabolites
will
be
significantly
more
toxic
than
the
parent,
but
can
not
exclude
them
as
being
significantly
less
toxic.
Since
these
metabolites
were
present
in
lettuce
at
about
the
same
level
as
the
parent,
MARC
suggested
that
the
risk
assessment
team
use
2X
the
parent
residue
levels
for
risk
assessment,
unless
field
trial
data
on
metabolites
on
related
crops
indicate
as
lower
ratio
is
appropriate.
For
tolerance
expression,
parent
only
is
adequate
to
serve
as
the
misuse
indicator.

Piperonyl
butoxide
is
currently
exempt
from
the
requirements
of
tolerances
when
applied
to
growing
crops
in
accordance
with
good
agricultural
practices
(
40
CFR
§
180.1001(
b)(
4)).
Results
of
studies
submitted
by
the
Task
Force
II
on
preharvest
uses
for
some
crops
(
based
on
a
reduced
number
of
field
trials)
show
detectable
and
variable
residues
of
piperonyl
butoxide
in/
on
nearly
all
raw
agricultural
commodities
tested.
Therefore,
additional
residue
data
reflecting
preharvest
uses
are
required
for
reregistration
and
tolerance
reassessment.
When
the
requested
data
have
been
evaluated,
HED
will
recommend
revocation
of
the
tolerance
exemption
in
40
CFR
§
180.1001(
b)(
4)
along
with
the
establishment
of
crop
group
tolerances,
if
appropriate.
The
established
tolerances
for
plant
commodities,
resulting
from
postharvest
uses,
are
currently
expressed
in
terms
of
piperonyl
butoxide
per
se.
Plant
tolerances
range
from
0.25
ppm
(
potato
and
sweet
potato)
to
20
ppm
(
most
cereal
grains).
The
available
data
are
inadequate
to
support
many
of
the
established
tolerances
resulting
from
postharvest
uses,
and
additional
data
are
required.

Livestock
The
HED
MARC
concluded
the
terminal
residue
of
concern
in
livestock
is
piperonyl
butoxide
per
se.
The
qualitative
nature
of
the
residue
in
ruminants
and
poultry,
resulting
from
Page
24
of
61
dermal
treatments,
is
adequately
understood.
However,
the
nature
of
the
residue
in
ruminants
and
poultry,
resulting
from
oral
treatments,
is
only
partially
understood.
The
oral
metabolism
studies
may
be
upgraded
to
acceptable
status
pending
further
characterization/
identification
of
radioactive
residues
in
certain
matrices/
fractions
(
data
are
under
review)
and
radiovalidation
of
the
enforcement
or
data­
collection
method
using
samples
from
either
the
dermal
or
oral
studies.
The
metabolism
of
PBO
in
lactating
goat
and
hen
poultry
following
dermal
administration
indicated
that
parent
is
the
major
metabolite
(>
30%
TRR
except
for
goat
kidney
and
liver).
There
are
no
specific
toxicity
concerns
for
all
metabolites,
which
with
few
exceptions
were
present
at
<
10%
TRR.
Since
the
major
route
of
exposure
would
most
likely
come
from
dermal
treatment
of
livestock
with
piperonyl
butoxide,
MARC
concluded
that
parent
only
is
the
residue
of
toxicological
concern
to
be
included
in
risk
assessment
and
tolerance
expression
.

Tolerances
of
0.25
ppm
for
milk
fat,
reflecting
negligible
residues
in
milk,
and
0.1
ppm
for
the
fat,
meat,
and
meat
byproducts
of
cattle,
goats,
hogs,
horses,
and
sheep
have
been
established.
Tolerances
of
1
ppm
for
eggs
and
3
ppm
for
the
fat,
meat,
and
meat
byproducts
of
poultry
have
been
established.
Additional
data
are
required
to
reassess
the
established
livestock
commodity
tolerances
and
estimate
residues
from
all
possible
exposure
scenarios
which
include
direct
application
to
livestock,
premise
treatment,
and
feeding
of
piperonyl
butoxide
treated
livestock
feed.

4.2.1.2
Residue
Analytical
Method
Plant
Commodities
The
Pesticide
Analytical
Manual
(
PAM)
Volume
II
lists
a
colorimetric
method
(
Method
II)
for
the
enforcement
of
tolerances
for
residues
of
piperonyl
butoxide
per
se
in/
on
plant
commodities.
An
improved
method,
HPLC/
fluorescence
method
has
been
proposed
to
replace
the
existing
colorimetric
method.
The
new
method
can
separately
determine
residues
of
piperonyl
butoxide
per
se
and
piperonyl
butoxide
metabolites
collectively
determined
as
hydroxymethyl
dihydrosafrol
(
HMDS).
The
HPLC/
fluorescence
method
has
been
subjected
to
a
successful
independent
laboratory
validation
and
has
been
forwarded
to
ACL/
BEAD
for
method
validation
by
Agency
chemists.
The
data­
collection
method
used
for
the
analysis
of
samples,
harvested
from
recent
studies
pertaining
to
magnitude
of
the
residue
and
storage
stability
studies,
was
the
same
HPLC/
fluorescence
method.

Livestock
Commodities
Under
Section
180.127,
PAM
Volume
II
lists
several
methods
for
the
enforcement
of
tolerances
for
residues
of
piperonyl
butoxide
per
se
in
animal
commodities.
The
gas
liquid
chromatography
methods
(
Method
I
and
Methods
A
and
B)
are
preferred
over
the
colorimetric
methods
(
Methods
C
and
D).
Using
the
GLC
methods,
residues
in
samples
of
milk
and
tissues
are
extracted
with
a
mixture
of
ethyl
alcohol,
ether,
and
hexane.
Determination
is
by
GLC
equipped
with
flame
ionization
detector
for
Methods
I
and
B,
and
electron
capture
detector
for
Page
25
of
61
Method
A.
The
sensitivity
of
each
method
is
0.005
ppm.
A
new
GC/
MS
method
has
been
proposed
for
enforcement
of
piperonyl
butoxide
tolerances
in
livestock
commodities.
The
LOQ
is
0.01
ppm
in
milk
and
eggs
and
0.05
ppm
in
livestock
tissue.

4.2.1.3Multiresidue
Methods
According
to
PAM
Volume
I,
piperonyl
butoxide
per
se
is
completely
recovered
by
multiresidue
method
Protocols
A
and
D.
A
recent
submission
confirms
that
head
lettuce
gave
acceptable
recoveries
for
piperonyl
butoxide
per
se
when
taken
through
the
complete
method
in
Protocol
A
using
401E1
+
C1
+
DL2.

4.2.1.4
Storage
Stability
Data
Plants
The
registrant
has
submitted
the
results
of
several
studies
which
depict
the
freezer
storage
stability
of
piperonyl
butoxide
in/
on
oilseeds,
nonoily
grains,
leafy
vegetables,
root
crops
and
fruits
and
fruiting
vegetables.
The
available
data
indicate
that
fortified
residues
of
piperonyl
butoxide
per
se
are
reasonably
stable
under
frozen
storage
conditions
in
some
commodities
but
residues
may
also
decline
in
some
matrices.
The
Agency
will
make
appropriate
adjustments
of
maximum
residues
observed
in
the
field
trials,
if
needed,
in
order
to
compensate
for
losses
resulting
from
storage.
Storage
stability
data
for
piperonyl
butoxide
per
se
are
required
for
oilseeds,
nonoily
grains,
and
root
crops.
The
requested
data
for
oilseeds
and
root
crops
should
reflect
maximum
intervals
of
30
and
21
months,
respectively,
and
data
for
nonoily
grains
should
reflect
the
storage
intervals
of
samples
from
the
outstanding
field
trials.

Processed
Commodities
Data
on
the
storage
stability
of
piperonyl
butoxide
residues
on
some
processed
commodities
have
been
submitted.
These
data
indicate
that
fortified
residues
of
piperonyl
butoxide
per
se
are
reasonably
stable
under
frozen
conditions
for
up
to
12
months
in
bean
cannery
waste;
tomato
juice,
puree,
and
wet
and
dry
tomato
pomace;
orange
juice,
dried
pulp,
and
molasses;
and
cotton
meal,
soapstock,
and
crude
oil.
The
available
data
do
not
fully
support
the
maximum
intervals
and
conditions
of
samples
from
existing
tomato,
orange,
and
cotton
processing
studies.
Therefore,
additional
storage
stability
data
for
the
processed
commodities
of
oilseeds,
grains,
and
fruits/
fruiting
vegetables
are
required.
The
requested
data
for
the
processed
commodities
of
fruits/
fruiting
vegetables
and
oilseeds
should
reflect
a
maximum
interval
of
31and
32
months,
respectively.
The
Piperonyl
Butoxide
Task
Force
II
has
indicated
that
a
storage
stability
study
for
many
processed
food/
feed
items
is
ongoing.
Page
26
of
61
Livestock
Commodities
No
storage
stability
data
are
available
for
piperonyl
butoxide
residues
of
concern
in
milk,
eggs,
and
livestock
tissues.
Therefore,
storage
stability
data
as
well
as
information
pertaining
to
the
storage
conditions
and
intervals
of
samples
have
been
requested
by
HED
Storage
stability
data
is
required
to
support
the
storage
intervals
and
sample
conditions
from
the
following
submitted
studies;
feeding
studies
for
dairy
cattle
and
poultry,
cattle
dermal
study,
and
poultry
premise
study.
For
the
dairy
cattle
and
poultry
oral
feeding
studies,
the
data
should
reflect
the
actual
storage
conditions
of
the
samples,
and
therefore
should
include
frozen
storage
as
tissue/
eggs/
milk,
storage
as
the
dried
extract,
and
storage
as
the
reconstituted
extract.

Water
Water
storage
stability
data
indicate
that
fortified
residues
of
piperonyl
butoxide
are
reasonably
stable
in
potable
water
under
frozen
storage
conditions
for
up
to
­
18
months.
The
collected
potable
water
samples
from
the
submitted
field
residue
trials
were
stored
frozen
for
­
19­
23
months
prior
to
residue
analysis.
The
registrants
have
indicated
that
additional
fortified
potable
water
samples
will
be
analyzed
to
encompass
the
maximum
storage
interval
of
samples
from
the
field
trials.

4.2.1.5Magnitude
of
the
Residue
in
Plants
Overall,
the
available
magnitude
of
the
residue
data
for
supported
food/
feed
commodities
are
inadequate
to
support
these
uses,
and
therefore,
additional
data
are
required
for
reregistration.
The
number
of
trials
required
to
support
preharvest
uses
is
listed
in
the
Product
and
Residue
Chemistry
assessment
(
T.
Morton,
D288366,
6/
29/
04).
Requirements
are
based
on
OPPTS
860.1500
GLN
for
data
needed
to
establish
crop
group
tolerances.
Since
the
bulk
of
piperonyl
butoxide
end­
use
products
sold
in
the
market
are
likely
applied
to
field­
growing
crops,
the
majority
of
the
required
trials
reflect
this
use
pattern.
However,
HED
cannot
estimate
the
residues
expected
following
applications
to
greenhouses
because
data
are
not
available.
Therefore,
the
Agency
recommends
that
additional
side­
by­
side
trials
be
conducted
to
determine
the
magnitude
of
residues
from
applications
to
greenhouse
grown
crops
(
e.
g.,
lettuce,
pepper,
and
tomato).
The
postharvest
uses
of
piperonyl
butoxide
on
many
crop
commodities
are
also
not
supported
by
adequate
residue
data.
The
Agency
prefers
that
residue
data
reflecting
both
preharvest
uses
and
postharvest
uses
be
submitted
for
crops
with
both
uses.

Piperonyl
butoxide
is
currently
exempt
from
the
requirements
of
tolerances
when
applied
to
growing
crops
in
accordance
with
good
agricultural
practices
(
40
CFR
§
180.1001(
b)(
4)).
When
the
requested
data
have
been
evaluated,
HED
will
recommend
revocation
of
the
tolerance
exemption
and
the
establishment
of
crop
group
tolerances
if
appropriate.
Page
27
of
61
4.2.1.6Magnitude
of
the
Residue
­
Food
Handling
Adequate
data
on
the
magnitude
of
residues
of
piperonyl
butoxide
per
se
in
food­
handling
establishments
and
food
storage
areas
are
available.
These
data
indicate
that
the
established
tolerance
of
10
ppm
will
not
be
exceeded
in
representative
food
commodities
and
surfaces
that
had
been
covered
during
treatments
using
representative
formulations.
The
Piperonyl
Butoxide
Master
Label
provides
adequate
instructions
for
removing
or
covering
food
during
treatment,
and
for
covering
all
food
processing
surfaces
treatment
and/
or
thoroughly
cleaned
surfaces
after
treatment
and
before
use.

No
data
are
available
to
support
uses
of
piperonyl
butoxide
on
foods
stored
in
multiwalled
paper
or
cloth
bags,
and
additional
data
are
required
for
reregistration.
The
required
data
should
depict
the
magnitude
of
residues
of
concern
in
representative
food
types
stored
in
multiwalled
paper
or
cloth
bags
following
surface
treatments
followed
by
space
treatments
followed
by
bag/
container
treatments
at
the
maximum
use
rate
for
each
application
type.
The
bag/
container
treatments
should
be
in
accordance
with
the
conditions
and
specifications
listed
in
40
CFR
§
180.127.
Alternatively,
the
use
of
piperonyl
butoxide
on
foods
stored
in
multi­
walled
paper
or
cloth
bags
may
be
removed
from
all
product
labels
along
with
the
revocation
of
the
associated
tolerance.

4.2.1.7Magnitude
of
the
Residue
in
Processed
Food/
Feed
Studies
depicting
magnitude
of
the
residues
of
piperonyl
butoxide
per
se
in
the
processed
commodities
of
cotton,
grape,
orange,
potato,
sugar
beet,
and
tomato
are
considered
adequate
pending
submission
of
supporting
storage
stability
data.
These
studies
indicate
that
piperonyl
butoxide
may
concentrate
in
certain
processed
commodities.
At
this
time,
HED
is
unable
to
recommend
appropriate
tolerance
levels
for
processed
commodities
which
showed
residue
concentration
because
the
nature
of
the
residue
in
plants
has
not
been
determined
and
the
highest
average
field
trial
residue
values
for
many
crop
commodities
have
not
been
determined.
Processing
studies
for
apple,
barley,
coconut,
corn
(
field),
fig,
flax,
oat,
peanut,
pineapple,
plum,
rice,
rye,
and
sorghum
are
required
for
reregistration.
The
required
data
should
depict
magnitude
of
residues
of
concern
in
each
of
the
processed
commodities
for
each
of
these
crops.
A
wheat
processing
study
has
been
submitted
but
deemed
incomplete
because
no
data
were
provided
for
wheat
bran,
middlings,
shorts,
and
germ.
A
new
wheat
processing
study
is
therefore
also
required
for
reregistration.
The
Piperonyl
Butoxide
Task
Force
II
has
indicated
that
a
storage
stability
study
for
many
processed
food/
feed
items
is
ongoing.

4.2.1.8Magnitude
of
the
Residue
in
Meat,
Milk,
Poultry,
and
Eggs
Based
upon
the
initial
results
of
studies
depicting
the
magnitude
of
the
residue
in
animals
and
observed
residues
in
feedstuff
from
preharvest
trials,
piperonyl
butoxide
residues
of
concern
are
expected
to
occur
in
meat,
milk,
poultry,
and
eggs.
Submitted
ruminant
studies
reflecting
dermal
and
oral
treatments
have
been
reviewed
and
deemed
inadequate
but
upgradeable.
The
Page
28
of
61
reviewed
studies
suggest
that
the
established
tolerances
for
milk
and
ruminant
tissues
are
too
low.
A
premise
spray
treatment
study
with
ruminants
is
also
now
required
for
reregistration
because
the
results
of
the
reviewed
premise
study
with
poultry
suggest
that
detectable
residues
at
or
near
the
tolerance
levels
are
expected
at
1X.
Submitted
poultry
studies
reflecting
oral
and
premise
spray
treatments
have
been
reviewed
and
deemed
inadequate
but
upgradeable.
In
addition,
a
study
reflecting
dip
treatment
of
piperonyl
butoxide
on
laying
hens
was
reviewed
and
determined
to
be
inadequate
because
it
does
not
reflect
the
supported
maximum
use
rate
for
direct
application
to
poultry.
Therefore,
a
study
reflecting
direct
applications
on
poultry
using
a
10%
dust
formulation
is
required
for
reregistration.

HED
would
have
preferred
that
the
magnitude
of
the
residue
study
for
livestock
reflect
all
possible
exposure
scenarios
which
include
direct
application
to
livestock,
premise
treatment,
and
consumption
of
treated
feed.
The
Agency
will
add
the
residues
from
all
possible
exposure
routes
when
the
additional
requested
data
have
been
submitted
and
reviewed.

4.2.1.9
Magnitude
of
the
Residue
in
Water,
Fish,
and
Irrigated
Crops
Under
current
policy,
EPA
is
not
establishing
tolerances
for
pesticides
in
potable
water
and
no
maximum
contaminant
level
(
MCL)
for
piperonyl
butoxide
in
potable
water
has
been
established.
The
Task
Force
II
has
submitted
data
depicting
magnitude
of
the
residue
of
piperonyl
butoxide
per
se
in
potable
water
from
trials
conducted
in
aquatic
environments
simulating
uses
of
the
pesticide
in
flooded
rice
fields.
In
its
review
of
the
study,
HED
concluded
that
if
the
aquatic
uses
of
piperonyl
butoxide
and
pyrethrins
are
limited
to
flooded
rice
fields
for
the
control
of
adult
mosquitos
only,
then
the
reregistration
requirements
for
GLN
860.1400
will
be
considered
fulfilled
pending
label
amendments
to
specify
a
minimum
holding
interval
or
EPA's
Office
of
Water
may
wish
to
establish
an
MCL
for
piperonyl
butoxide
in
potable
water.

4.2.1.10
Confined
and
Field
Accumulation
in
Rotational
Crops
A
confined
rotational
crop
study
(
OPPTS
860.1850)
is
required
to
determine
the
nature
and
amount
of
pesticide
residue
uptake
in
rotational
crops
as
well
as
appropriate
rotational
crop
restrictions.
A
field
accumulation
study
in
rotational
crops
(
OPPTS
860.1900)
is
required
if
the
level
of
the
total
radioactive
residue
in
the
confined
rotational
crops
is
equal
to
or
exceeds
0.01
ppm
at
the
desired
rotational
interval
or
at
12
months,
whichever
is
shorter,
and
once
the
nature
of
the
residue
in
the
rotational
crops
is
understood.

4.2.1.11
Codex
Harmonization
The
Codex
Alimentarius
Commission
has
established
several
maximum
residue
limits
(
MRLs)
for
residues
of
piperonyl
butoxide.
The
Codex
MRLs
are
expressed
in
terms
of
Piperonyl
butoxide
per
se
which
is
identical
to
the
current
U.
S.
tolerance
expression.
A
numerical
comparison
of
the
Codex
MRLs
and
the
corresponding
current
U.
S.
tolerances
for
piperonyl
Page
29
of
61
butoxide
is
presented
in
the
Product
and
Residue
Chemistry
assessment
(
T.
Morton,
D288366,
6/
29/
04).

4.2.2
Dietary
Exposure/
Risk
Assessment
4.2.2.1
Consumption
Data
and
Dietary
Risk
Analysis
Piperonyl
butoxide
chronic
dietary
exposure
assessments
were
conducted
using
two
peer
reviewed
software
models,
the
Lifeline
 
model
(
Version
2.0),
and
the
Dietary
Exposure
Evaluation
Model
software
with
the
Food
Commodity
Intake
Database
(
DEEM­
FCID
 
,
Version
2.03).
Both
models
incorporate
consumption
data
from
USDA's
Continuing
Surveys
of
Food
Intakes
by
Individuals
(
CSFII),
1994­
1996
and
1998.
The
1994­
96,
98
data
are
based
on
the
reported
consumption
of
more
than
20,000
individuals
over
two
non­
consecutive
survey
days.

The
Lifeline
 
and
DEEM
 
programs
convert
raw
agricultural
commodity
(
RAC)
residues
into
residues
in/
on
foods
as
eaten
or
consumed
based
on
recipes
of
raw
ingredients
for
each
food
item.
Lifeline
 
converts
the
RAC
residues
by
randomly
selecting
a
RAC
residue
value
from
the
residue
distribution
and
calculating
a
net
residue
for
that
food
based
on
the
ingredients'
mass
contribution
to
that
food
item.
Lifeline
 
models
the
individuals's
dietary
exposures
over
a
season
by
selecting
a
new
CSFII
diary
each
day
from
a
set
of
similar
individuals
based
on
age
and
season
attributes
and
grouping
the
dairies
based
on
age
and
the
season.
This
probabilistic
methodology
is
used
to
estimate
both
acute
and
chronic
dietary
exposures
in
Lifeline
 
.

In
DEEM
 
,
consumption
data
are
averaged
for
the
entire
U.
S.
population
and
within
population
subgroups
for
chronic
exposure
assessment,
but
are
retained
as
individual
consumption
events
for
acute
exposure
assessment.
DEEM
 
estimates
chronic
dietary
exposure
by
estimating
the
residue
level
in
each
treated
food/
food
form,
multiplying
that
estimate
by
the
average
daily
consumption
estimate
for
that
food/
food
form,
and
summing
residue
intake
estimates
for
all
food/
food
forms
to
arrive
at
a
total
average
estimated
exposure.
For
acute
exposures
DEEM
 
uses
individual
on­
day
food
consumption
data
on
an
individual
by
individual
basis.
The
reported
consumption
amounts
of
each
food
item
are
matched
in
multiple
random
pairings
with
reside
values
and
them
summed
in
a
probabilistic
acute
dietary
exposure
assessment.

Both
the
acute
and
chronic
dietary
exposure/
risk
analyses
for
piperonyl
butoxide
were
conducted
using
a
highly
refined
dietary
exposure
assessment
for
all
supported
food
uses.
USDA
Pesticide
Data
Program
(
PDP)
data
were
used
for
commodities
which
have
a
preharvest
registered
uses
and
for
cereal
grain
crops
which
have
a
stored
grain
use.
All
other
commodities
were
assigned
residues
from
either
the
simulated
warehouse
space
spray
experiment
or
the
simulated
restaurant
experiment.
Residue
data
from
dermal
treatment
of
livestock
studies
were
used
for
meat,
milk
poultry,
and
eggs
because
dermal
treatment
of
livestock
is
the
most
likely
route
of
exposure
for
humans.
For
risk
assessment
purposes,
the
terminal
residues
of
concern
for
plants
include
the
parent
and
a
factor
to
account
for
metabolites.
Based
on
recommendations
Page
30
of
61
from
the
HED
MARC,
residues
were
estimated
at
2X
the
parent
residue
to
account
for
metabolites
unless
field
trial
data
on
metabolites
on
related
crops
indicate
that
a
lower
ratio
is
appropriate.
For
risk
assessment
purposes,
the
terminal
residue
of
concern
in
livestock
is
piperonyl
butoxide,
per
se.
Available
data
from
processing
studies
were
used
for
processed
commodities.
Percent
crop
treated
(
CT)
was
used
for
all
commodities
for
which
%
CT
data
are
available.
Where
no
percent
CT
data
are
available,
the
dietary
analyses
assumes
100%
CT.
(
T.
Morton,
6/
30/
04,
D296887).

4.2.2.2
Acute
Dietary
Exposure/
Risk
Assessment
The
highly
refined
probabilistic
acute
dietary
exposure
assessment
was
conducted
for
all
supported
piperonyl
butoxide
food
uses
and
dietary
risk
estimates
are
provided
for
the
general
U.
S.
population
and
various
population
subgroups.
This
assessment
concludes
that
for
all
supported
commodities,
the
acute
dietary
exposure
estimates
are
below
HED's
level
of
concern.
The
acute
dietary
exposure
estimate
for
the
highest
exposed
population
subgroup,
children
1­
2
years
of
age,
is
20%
of
the
aPAD.
Results
of
the
acute
dietary
exposure
analysis
are
presented
in
Table
6.

Table
6.
Piperonyl
Butoxide
Acute
Dietary
(
Food)
Exposure
Estimate
and
Percent
of
Acute
RfD
Population
Subgroup
aPAD
(
mg/
kg/
day)
Exposure
(
mg/
kg/
day)
99.9th
percentile
%
aPAD
99.9th
percentile
DEEM­
FCID
Lifeline
DEEM­
FCID
Lifeline
General
U.
S.
Population
6.3
0.2825
0.3761
4
6
All
Infants
(<
1
year
old)
0.1550
0.3908
2
6
Children
1­
2
years
old
0.6473
1.2296
10
20
Children
3­
5
years
old
0.4805
0.8027
8
13
Children
6­
12
years
old
0.3639
0.4112
6
7
Youth
13­
19
years
old
0.2005
0.3446
3
5
Adults
20­
49
years
old
0.1772
0.3030
3
5
Adults
50+
years
old
0.1818
0.2865
3
5
Females
13­
49
years
old
0.1768
0.3467
3
6
4.2.2.3
Chronic
Dietary
Exposure/
Risk
Assessment
The
highly
refined
chronic
dietary
exposure
assessment
was
conducted
for
all
supported
piperonyl
butoxide
food
uses
for
the
general
U.
S.
population
and
various
population
subgroups.
This
assessment
concludes
that
for
all
supported
commodities,
the
chronic
dietary
exposure
estimates
are
below
HED's
level
of
concern.
The
chronic
dietary
exposure
estimate
for
the
highest
exposed
population
subgroup,
children
1­
2
years
of
age,
is
12%
of
the
cPAD.
Results
of
the
chronic
dietary
exposure
analysis
are
presented
in
Table
7.
Page
31
of
61
Table
7.
Piperonyl
Butoxide
Chronic
Dietary
(
Food)
Exposure
Estimate
and
Percent
of
Chronic
RfD
Population
Subgroup
cPAD
(
mg/
kg/
day)
Exposure
(
mg/
kg/
day)
%
cPAD
DEEM­
FCID
Lifeline
DEEM­
FCID
Lifeline
General
U.
S.
Population
0.155
0.0078
0.0075
5
5
All
Infants
(<
1
year
old)
0.0034
0.0057
2
4
Children
1­
2
years
old
0.0182
0.0185
12
12
Children
3­
5
years
old
0.0169
0.0163
11
11
Children
6­
12
years
old
0.0130
0.0117
8
8
Youth
13­
19
years
old
0.0062
0.0059
4
4
Adults
20­
49
years
old
0.0063
0.0064
4
4
Adults
50+
years
old
0.0060
0.0066
4
4
Females
13­
49
years
old
0.0063
0.0070
4
5
4.3.
Drinking
Water
Exposure/
Risk
Pathway
4.3.1.
Environmental
Fate
Assessment
Environmental
fate
studies
indicated
that
piperonyl
butoxide
is
moderately
mobile
in
soilwater
systems.
Lab
studies
indicated
that
piperonyl
butoxide
degrades
in
the
environment
by
photolysis
in
water
(
half­
life
8.4
hours),
and
is
metabolized
by
soil
microorganisms
(
half­
life
14
days).
The
aqueous
photolysis
route
may
be
significant
for
piperonyl
butoxide
due
to
its
use
in
mosquito
control
applications
over
intermittently
flooded
areas.
The
major
degradates
of
piperonyl
butoxide
are
piperonyl
butoxide­
alcohol,
­
aldehyde,
and
­
acid
(
Attachment
1).
These
degradates
are
expected
to
be
more
soluble
in
water
and
therefore
more
mobile
in
soil­
water
systems
than
the
parent,
based
on
their
lower
molecular
weights
and
hydrophilic
moieties.
Based
on
the
structural
similarity,
HED's
MARC
believes
that
these
three
degradates
will
likely
share
the
same
toxicity
as
the
parent.
Therefore,
MARC
recommended
that
these
three
degradates
be
included
in
the
drinking
water
assessment.
There
are
no
specific
toxicity
concerns
for
all
other
minor
metabolites
(
T.
Morton,
D304469,
6/
30/
04).

4.3.2
Estimated
Environmental
Concentrations
Monitoring
data
are
not
available
to
assess
residues
of
piperonyl
butoxide
and
piperonyl
butoxide
in
drinking
water.
Therefore,
the
EFED
performed
a
Tier
I
drinking
water
assessment
for
piperonyl
butoxide
in
surface
water
and
groundwater
(
W.
Eckel,
D286223,
5/
17/
04).
EFED
used
the
FIRST
model
for
estimating
the
upper
bound
on
the
concentrations
that
could
occur
in
surface­
water­
source
drinking
water,
and
the
SCI­
GROW
model
to
estimate
the
concentrations
in
ground
water
used
for
drinking
water.
The
drinking
water
assessment
focuses
on
the
terrestrial
agricultural
uses
of
piperonyl
butoxide
since
they
are
considered
more
likely
to
contaminate
drinking
water
sources.
The
cranberry,
mosquito
adulticide
and
carp
bait
uses
are
not
considered,
although
each
has
the
potential
to
contaminate
water,
because
EFED
does
not
have
standard
Page
32
of
61
methods
for
estimating
drinking
water
contamination
from
these
use
patterns.
Estimated
drinking
water
concentrations
are
presented
in
Table
8.

Table
8.
Drinking
Water
EDWCs
for
Piperonyl
Butoxide
Drinking
Water
Source
Acute
(
ug/
L)
Chronic(
ug/
L)

Surface
Water
240
60
Groundwater
0.26
0.26
4.3.2.1
Surface
Water
The
FIRST
model
was
used
to
estimate
environmental
concentrations
in
drinking
water
from
surface
water.
FIRST
is
a
screening
model
and
produces
upper
bound
values
of
drinking
water
concentrations.
It
is
based
on
a
real
reservoir
in
Illinois.
It
is
a
single
event
model
which
assumes
that
a
single
run­
off
moves
a
percentage
of
the
applied
pesticide
into
the
pond.
Input
parameters
used
for
the
surface
water
analysis
are
summarized
in
Table
9.
The
peak
and
mean
surface
water
EDWCs
for
piperonyl
butoxide
are
240
and
60
ug/
L
respectively.

4.3.2.2
Groundwater
EFED
used
the
Screening
Concentration
in
Ground
Water
(
SCI­
GROW)
model
to
estimate
piperonyl
butoxide
concentrations
in
groundwater
contaminated
by
terrestrial
uses.
SCIGROW
is
a
regression­
based
model
that
uses
few
input
parameters:
pesticide's
organic
carbon
partition
coefficient
(
K
oc
),
aerobic
soil
degradation
half­
life,
and
product
label
application
rate
and
frequency
(
Barrett,
1997).
It
provides
a
groundwater
screening
concentration
for
use
in
determining
potential
risk
to
human
health
from
drinking
water
contaminated
with
a
pesticide.
The
groundwater
concentration
is
estimated
based
on
the
maximum
application
rates
in
areas
where
groundwater
is
exceptionally
vulnerable
to
contamination.
These
vulnerable
areas
are
characterized
by
high
rainfall,
rapidly
permeable
soil,
and
shallow
aquifer.
Input
parameters
are
summarized
in
Table
9.
The
peak
and
mean
groundwater
EDWCs
for
piperonyl
butoxide
are
0.26
ug/
L.

Table
9.
FIRST
and
SCI­
GROW
Input
Parameters
for
Piperonyl
butoxide
Input
Parameter
Value
Application
Rate
0.5
lb,
ten
times,
at
3­
day
intervals
Application
type
Aerial
spray
(
16%
drift)
or
ground
spray
(
6.4%
drift)
Unincorporated
Laboratory
Soil
Metabolism
Half­
life
73
days
(
3
x
single
value
of
24.2
days)

Laboratory
Aerobic
Aquatic
Metabolism
Half­
life
399
days
(
3
x
single
values
of
133
days)

Laboratory
Hydrolysis
Half­
life
(
pH
7)
stable
Laboratory
Aqueous
Photolysis
Half­
life
5.07
days
Table
9.
FIRST
and
SCI­
GROW
Input
Parameters
for
Piperonyl
butoxide
Input
Parameter
Value
Page
33
of
61
Soil­
Water
Partitioning
Coefficient
(
Koc)
FIRST:
399
(
lowest
non­
sand
Koc)
SCI­
GROW:
599
(
median
Koc)

Solubility
14.3
ppm
(
parent)

Percent
Cropped
Area
87%

5.0
RESIDENTIAL
EXPOSURE
AND
RISK
Based
on
the
Master
Label,
14
residential
exposure
scenarios
have
been
assessed
for
this
RED.
Only
inhalation
and
incidental
ingestion
exposure
assessments
have
been
conducted
for
the
residential
scenarios.
Dermal
exposures
were
not
assessed
because
no
dose
or
endpoints
were
selected
for
dermal
exposure.
Acute,
and
short­
and
intermediate­
term
exposures
are
expected/
assessed
for
residential
exposure
scenarios
based
on
use
and
exposure
patterns.
Acute
exposures
are
assessed
for
post­
application
inhalation
exposure
to
aerial
and
curbside
mosquito
abatement
applications
and
for
exposures
during
and
after
application
of
aerosol
space
sprays
indoors.
Short
and
intermediate
term
exposures
are
assessed
for
all
other
handler
and
postapplication
exposure
scenarios.
(
B.
Daiss,
D313107,
8/
05;
M
Crowley,
D315334,
8/
05)

5.1
Residential
Exposure
Scenarios
The
residential
exposure
assessment
includes
three
handler
and
eleven
post­
application
residential
exposure
scenarios.
The
term
"
handler"
applies
to
individuals
who
mix,
load,
and
apply
the
pesticide
product.
The
term
"
post­
application"
describes
individuals
who
are
exposed
to
pesticides
after
entering
areas
previously
treated
with
pesticides.
Based
on
information
provided
in
the
Master
Label
regarding
current
registrant
supported
uses,
HED
assessed
the
following
residential
exposure
scenarios
for
the
piperonyl
butoxide
RED.

Application
of
dust
with
shaker
can,
bulb
duster,
and
power
duster,
a
relevant
and
potentially
significant
exposure
scenario,
was
not
assessed
due
to
lack
of
dust­
specific
or
adequate
surrogate
data
on
inhalation
exposure
associated
with
this
activity.
Additionally,
HED
did
not
conduct
a
quantitative
assessment
of
potential
exposure
from
indoor
misters
due
to
data
limitations.
However,
HED
recommends
that
the
use
restrictions,
both
general
and
specific,
prescribed
by
the
master
label
be
required
for
all
labels
for
indoor
misters
that
contain
PBO.
These
restrictions
include
the
following:
general
use
restrictions
­
do
not
apply
when
other
persons
are
present,
do
not
apply
when
pets
(
except
fish)
are
present,
remove
or
cover
exposed
food
and
wataer
before
application,
remove
or
cover
dishes,
utensils,
food
processing
equipment,
and
food
preparation
surfaces
or
wash
them
thoroughly
before
use,
do
not
breathe
dust,
vapors,
or
spray
mist;
specific
metered
release
application
use
restrictions
­
do
not
use
in
nurseries
or
rooms
where
infants,
ill
or
aged
persons
are
confined,
do
not
place
metering
device
directly
over
or
within
8
feet
of
exposed
foods,
dishes,
utensils,
food
processing
equipment,
and
food
handling
or
prepartion
areas.
It
should
be
noted
that
a
screening
assessment
of
indoor
misters
was
Page
34
of
61
conducted
for
the
pyrethrin
risk
assessment.
HED
believes
the
pyrethrin
assessment
provides
support
for
the
label
restrictions
listed
above
for
indoor
misters.
(
T.
Dole,
D318630,
9/
05)

5.1.1
Handler
Exposure
Scenarios
1)
Mixing,
loading,
and
applying
liquid
spray
formulation
by
low­
pressure
handwand
for
indoor
surface
spray
application
2)
Mixing,
loading,
and
applying
liquid
spray
formulation
by
low­
pressure
handwand
for
indoor
crack
and
crevice
treatment
3)
Mixing,
loading,
and
applying
liquid
spray
formulation
by
hose­
end
sprayer
for
lawn
and
garden
application
4)
Mixing
and
loading
liquid
formulations
for
the
systems'
holding
tanks
for
outdoor
automatic
mister
systems
5.1.2
Postapplication
Exposure
Scenarios
1)
Inhalation
exposure
from
application
of
mosquito
adulticide
from
fixed
wing
aircraft
and/
or
helicopter
2)
Inhalation
exposure
from
application
of
mosquito
adulticide
from
ULV
truck
mounted
sprayer
3)
Toddler
incidental
ingestion
of
residue
from
treated
turf
grass
via
hand­
to­
mouth
activities
4)
Toddler
incidental
ingestion
of
residue
via
object­
to­
mouth
activity
while
on
treated
turf
grass
5)
Toddler
incidental
ingestion
of
soil
from
treated
area
6)
Toddler
incidental
ingestion
of
residues
deposited
on
carpet
via
hand­
to­
mouth
activities
after
use
of
total
release
foggers
7)
Toddler
incidental
ingestion
of
residues
deposited
on
vinyl
flooring
via
hand­
to­
mouth
activities
after
use
of
total
release
foggers
8)
Toddler
incidental
ingestion
of
residues
on
pets
via
hand­
to­
mouth
activities
after
pet
treatment
9)
Inhalation
exposure
to
aerosol
spray
during
and
after
space
spray
application
10)
Bystander
acute
inhalation
exposure
during
outdoor
automatic
mister
applications
11)
Bystander
short­
term
inhalation
exposure
during
outdoor
automatic
mister
applications
5.2
Residential
Exposure
Data
and
Assumptions
5.2.1
Application
Parameters
Application
rates
for
all
of
the
exposure
scenarios
assessed
are
based
on
information
provided
in
the
Piperonyl
Butoxide
Master
Label
submitted
to
the
Agency
by
the
Piperonyl
Butoxide
Task
Force
II
in
February
2003.
The
Master
Label
provides
application
parameters
including
type
of
application,
maximum
application
rate
or
concentration,
and
use
restrictions
pertinent
to
human
exposure
and
environmental
exposure.
The
Piperonyl
Butoxide
Master
Label
Page
35
of
61
lists
all
of
the
uses
that
the
Piperonyl
Butoxide
Task
Force
II
members
are
supporting.
Therefore,
it
is
important
all
labels
be
revised
to
reflect
the
supported
uses
and
maximum
allowable
application
rates
provided
in
the
Master
Label.
For
the
outdoor
automatic
mister
scenario,
the
application
rate
(
lb
ai/
gal
soln)
used
is
from
a
product
label
assumed
to
represent
typical
automatic
mister
systems.

5.2.2
Handler
Exposure
Data
It
is
the
policy
of
the
HED
to
use
data
from
the
Pesticide
Handlers
Exposure
Database
(
PHED)
or
Occupational
and
Residential
Exposure
Task
Force
(
ORETF)
data
to
assess
handler
exposures
for
regulatory
actions
when
chemical­
specific
monitoring
data
or
other
handler­
specific
data
are
not
available.
PHED
was
designed
by
a
task
force
of
representatives
from
the
US.
EPA,
Health
Canada,
the
California
Department
of
Pesticide
Regulation,
and
members
of
the
American
Crop
Protection
Association.
Currently,
the
database
contains
values
for
over
1,700
monitored
individuals
(
i.
e.,
replicates).
The
ORETF
completed
four
studies
which
were
designed
to
provide
representative
surrogate
exposure
data
for
pesticide
handler
risk
assessment.
The
studies
monitored
professionals
applying
granular
formulation
by
push
spreader
and
various
formulations
by
pressurized
hose­
end
"
handgun"
or
spray
gun;
and
volunteers
representing
non­
professional
consumers
applying
granular
formulation
by
push
spreader
and
liquid
formulations
by
garden
hose­
end
sprays.
Overall,
the
four
ORETF
studies
were
well­
conducted
and
the
data
for
all
scenarios
is
considered
of
better
quality
and
quantity
than
what
is
currently
contained
in
PHED.

Data
from
the
PHED
and/
or
ORETF
data
bases
were
used
to
assess
residential
handler
exposures.
Default
application
assumptions
regarding
areas
treated
or
amounts
applied
for
residential
handler
scenarios
are
documented
in
the
HED
Science
Advisory
Committee
on
Exposure
SOP
12:
"
Recommended
Revisions
To
The
Standard
Operating
Procedures
For
Residential
Exposure
Assessment"
(
2/
22/
2001).

5.2.3
Post­
application
Exposure
Data
5.2.3.1
HED
Residential
Exposure
SOPs
The
default
factors
used
for
the
assessment
are
taken
from
the
Exposure
Science
Advisory
Committee
SOP
12.
SOP
12
provides
values
to
assess
post
application
inhalation
and
non­
dietary
ingestion
exposure
to
lawn
care
pesticides,
and
indoor
broadcast
and
crack
and
crevice
treatments.

5.2.3.2
Non­
Dietary
Exposure
Task
Force
Exposure
Data
Primary
assumptions
for
assessing
post­
application
exposure
to
use
of
foggers
and
aerosols
in
indoor
residential
settings
were
based
on
data
provided
by
the
Non­
Dietary
Exposure
Task
Force
(
NDETF).
The
NDETF
was
formed
in
1996
from
members
of
the
Pyrethrin
Joint
Page
36
of
61
Venture
(
PJV)
and
Piperonyl
Butoxide
Task
Force
II,
Task
Forces
set
up
in
the
1980s
by
producers,
formulators,
and
marketers
of
the
AIs
to
respond
to
reregistration
needs.
NDETF
includes;
Bayer
CropSciences,
Botantical
Resources
Australia,
Endura
S.
p.
A,
McLaughlin
Gormley
King
Company,
Pyrethrum
Board
of
Kenya
Prentiss
Inc.,
S.
C.
Johnson
and
Son,
Inc.,
and
Valent
BioSciences
Corporation.
NDETF's
purpose
is
to
produce
scientifically
sound
data
on
non­
dietary
exposures
to
pyrethrin,
the
pyrethroids,
piperonyl
butoxide,
and
MGK­
264.

5.2.3.3
Spray
Drift
Task
Force
Exposure
Data
HED
used
the
AgDRIFT
model
to
calculate
airborne
concentrations
from
aerial
ULV
applications.
The
model
was
developed
by
the
Spray
Drift
Task
Force,
a
coalition
of
pesticide
registrants
whose
primary
objective
was
to
develop
a
comprehensive
data
base
of
off­
target
spray
drift
information
along
with
an
appropriate
modeling
system.
The
model
has
been
peer
reviewed
by
EPA's
Science
Advisory
Panel
and
has
been
used
in
previous
mosquito
adulticide
exposure
assessments
(
e.
g.
carbaryl,
malathion).

5.2.4
Exposure
Assumptions
The
following
assumptions
were
used
in
estimating
risks
from
residential
exposure
to
piperonyl
butoxide:

°
Average
body
weight
of
an
adult
is
70
kg
°
Average
body
weight
of
an
toddler
is
15
kg
°
Exposure
is
assessed
on
day
of
application
(
i.
e.,
day
zero)
°
Exposure
duration
is
short­
and
intermediate­
term
unless
otherwise
indicated
(
i.
e.,
acute
exposures
for
mosquito
and
indoor
space
spray
scenarios)
°
Maximum
application
rates
as
provided
by
the
Piperonyl
Butoxide
Task
Force
II
were
used
for
all
types
and
methods
of
application
For
outdoor
automatic
mister
systems,
application
rates
(
lb
ai/
ft3)
from
product
labels
are
assumed
to
represent
typical
automatic
systems
°
Maximum
daily
volumes
handled
and/
or
area
treated
are
as
follows
­
0.5
acre
is
used
to
represent
the
surface
area
treated
for
broadcast
applications
to
lawns
using
garden
hose­
end
sprayer;
­
average
home
treated
with
space
spray
or
crack
and
crevice
treatment
has
1600
square
feet
of
surface
area
­
holding
tank
size
for
outdoor
automatic
mister
systems
is
55
gallons
and
250
gallons
based
on
information
provided
to
SRRD
from
the
registrants.
It
is
assumed
that
a
homeowner
can
prepare
the
dilute
solution
and
re­
fill
the
holding
tank;
1
holding
tank
is
filled
per
day.
°
Mosquito
Abatement
Scenario
­
for
aerial
application
@
fixed
wing
aircraft
release
height
is
100
feet
@
rotary
aircraft
release
height
is
30
feet
Page
37
of
61
@
average
droplet
size
is
50
microns
(
per
label
and/
or
Public
Health
Pesticide
Applicator
Manual
(
25­
50
microns))

@
wind
speed
is
2
mph
(
per
label
and/
or
Applicator
Manual
(<
10
mph))

@
temperature
is
86
°
F
(
per
label
and/
or
pesticide
Applicator
Manual
(
50­
95
°
F))
­
for
truck
mounted
ULV
spray
application
a
dilution
factor
of
0.01
is
applied
to
the
airborne
concentration
at
the
maximum
application
rate
(
i.
e.,
1%
of
product
released
is
available
for
exposure)
­
breathing
zone
airborne
concentration
is
estimated
to
be
approximately
4­
6
ft
from
the
ground
­
adult
breathing
rate
is
1.0
m3
per
hour;
child
breathing
rate
is
0.8
m3
per
hour
(
NAFTA
breathing
rates
for
light
activity)
­
exposure
duration
is
<
2
hours
­
exposure
is
assessed
as
an
acute
exposure
°
Toddler
Outdoor
(
turf)
and
Indoor
Fogger
(
carpet
and
vinyl)
Hand
to
Mouth
Scenario
­
estimated
turf
transferable
residue
is
assumed
to
be
5%
of
the
maximum
application
rate
for
sprays
­
indoor
surface
residue
is
10
µ
g/
cm2
based
on
NDETF
study
data
and
a
maximum
application
rate
of
0.033
lbs
ai/
1000
ft3
for
indoor
foggers
­
hand
transfer
efficiency
is
13%
for
carpet;
8%
for
vinyl
based
on
NDETF
data
­
saliva
extraction
factor
is
50
percent
­
surface
portion
of
hand
put
in
mouth
is
20
cm2
­
hand­
to­
mouth
exposure
frequency
is
20
times
per
hour
­
saliva
extraction
factor
is
50
percent
­
Exposure
duration
is
2
hours
°
Toddler
Object
to
Mouth
Scenario
­
object
to
mouth
transfer
efficiency
is
equal
to
20%
of
the
application
rate
­
ingestion
rate
of
residues
from
mouthing
turf
or
a
small
object
is
25
cm2
°
Toddler
Incidental
Soil
Ingestion
Scenario
­
soil
ingestion
rate
is
100
mg/
day
­
fraction
of
ai
available
in
uppermost
cm
of
soil
(
fraction/
cm)
is
100
percent
based
on
soil
incorporation
into
top
1
cm
of
soil
after
application
°
Toddler
Pet
Treatment
Hand
to
Mouth
Scenario
­
one
half
of
a
16
oz
spray
container
is
used
to
treat
each
animal
­
transferable
residue
from
a
treated
pet
is
assumed
to
be
20%
of
the
maximum
application
rate
for
sprays
­
surface
area
of
a
treated
(
30
lb)
dog
is
6000
cm2
(
EPA
1993
Wildlife
Exposure
Factors
Handbook
­
carbaryl)
­
saliva
extraction
factor
is
50
percent
­
surface
portion
of
hand
put
in
mouth
is
20
cm2
­
frequency
of
hand­
to­
mouth
events
is
one
per
day
(
frequency
modified
to
reflect
transferable
residue
assumption
which
is
based
on
a
5
minute
heavy
rubbing/
petting
technique
that
would
lead
to
significantly
higher
hand
concentrations
than
would
result
from
a
single
contact)
Page
38
of
61
°
Inhalation
during
and
after
aerosol
space
spray
application
­
@
one
16
oz
spray
can
containing
likely
maximum
of
2.5%
ai
is
used
per
application
@
one
application
per
home
­
adult
breathing
rate
is
1.0
m3
per
hour;
child
breathing
rate
is
0.8
m3
per
hour
­
exposure
duration
is
<
2
hours
°
Acute
inhalation
exposure
to
residential
bystanders
from
outdoor
automatic
misters
­
all
active
ingredient
is
assumed
to
be
"
thrown
up"
in
the
air
immediately
and
available
for
exposure
(
100%
active
ingredient
available)
for
the
entire
exposure
duration
­
adult
breathing
rate
is
1.0
m3
per
hour;
child
breathing
rate
is
0.7
m3
per
hour
­
nozzle
height
outdoors
is
assumed
to
be
8
feet
from
the
ground
­
exposure
duration
is
assumed
to
be
1
minute
per
day
(
0.0167
hours/
day)
 
the
entire
duration
of
a
nozzle
spray
­
exposure
is
assumed
to
encompass
1,
1­
minute
spray
event
that
occurs
in
the
morning
or
evening
(
i.
e.,
exposure
is
to
air
concentration
following
1,
1­
minute
spray
event).
Note:
this
is
assumed
to
be
a
conservative
estimate
for
acute
exposure
duration
(
i.
e.,
labels
indicate
spray
durations
may
be
less
 
20­,
or
30­
seconds)
°
Short­
term
inhalation
exposure
to
residential
bystanders
from
outdoor
automatic
misters
­
all
active
ingredient
is
assumed
to
be
"
thrown
up"
in
the
air
immediately
and
available
for
exposure
(
100%
active
ingredient
available)
for
the
entire
exposure
duration
­
adult
breathing
rate
is
1.0
m3
per
hour;
child
breathing
rate
is
0.7
m3
per
hour
­
nozzle
height
outdoors
is
assumed
to
be
8
feet
from
the
ground
­
exposure
duration
is
assumed
to
be
5
hours
per
day
for
adults
and
3
hours
per
day
for
toddlers
­
Exposure
is
assumed
to
encompass
2,
1­
minute,
or
2,
30­
second
spray
events
that
occur
in
the
morning
or
evening
and
are
also
assumed
to
occur
within
the
5­
hour
or
3­
hour
exposure
duration
interval
(
i.
e.,
exposure
is
to
total
air
concentration
following
2,
1­
minute,
or
2,
30­
second
spray
events)

Non­
Standard
Exposure
Assumptions
Substance
and
scenario
specific
data
from
the
NDETF
study
was
used
to
determine
deposition
of
piperonyl
butoxide
on
vinyl
and
carpet
flooring
following
use
of
a
total
release
indoor
fogger.
Post­
fogger
release
floor
concentration
was
estimated
based
on
data
from
NDETF
Study
Volume
2,
"
Post­
Application
Deposition
Measurements
for
Pyrethrins
&
Piperonyl
Butoxide
Following
Use
of
a
Total
Release
Indoor
Fogger".
Transfer
of
piperonyl
butoxide
from
fogger
treated
carpet
was
assumed
to
be
13%
of
deposition
based
on
data
from
Volume
29
of
the
NDETF
Study,
"
Measurement
of
Transfer
of
Permethrin
and
Piperonyl
Butoxide
Residues
from
Vinyl
and
Carpet
Flooring
Treated
with
a
Fogger
Formulation
to
DSS
Wetted
Hands
Following
a
Single
Hand
Press".
Indoor
air
concentration
for
the
period
during
and
after
aerosol
space
spray
application
was
assumed
to
be
6
mg
per
cubic
meter
based
on
data
from
Volume
18
of
the
NDETF
Study,
"
Measurement
of
Air
Concentration
,
Dermal
Exposure,
and
Deposition
of
Pyrethrin
and
Piperonyl
Butoxide
Following
the
Use
of
an
Aerosol
Spray".
Page
39
of
61
The
approach
for
estimating
air
concentrations
from
truck­
mounted
ULV
spray
applications
is
based
on
a
modification
of
the
SOP
for
residential
exposure
assessment
for
inhalation
exposure
from
use
of
an
outdoor
space
spray
for
pest
control.

Specific
reference
to
"
automatic
mister
systems"
is
not
made
in
the
Piperonyl
Butoxide
Master
Label
however
there
is
reference
to
use
of
PBO
in
outdoor
domestic
sites
as
a
general,
crack­
and­
crevice,
or
spot
surface
spray.
Four
PBO­
containing
products
(
EPA
Reg.
No.
1021­
1785,
21165­
24,1021­
1800,
and
655­
797)
identified
in
a
Consumer
Specialty
Products
Association
(
CSPA)
discussion
paper
(
CSPA,
2005),
reference
specific
nozzle
spray
systems
used
in
outdoor
residential
sites.
The
following
is
additional
general
use
information
from
the
CSPA
discussion
paper:
holding
tanks
or
reservoirs
are
typically
plastic
with
30,
55,
or
250
gallon
capacity;
nozzle
height
is
approximately
8
 
10
feet;
nozzle
spacing
is
approximately
10
 
15
feet
apart
along
fences
or
foliage
(
i.
e.,
perimeter
separation);
automatic
dispersions
are
set
for
2
to
4
times
per
day
for
30
to
60
seconds
per
event;
systems
can
be
activated
manually
by
homeowners.

5.3
Residential
Exposure
and
Risk
Estimates
A
target
MOE
of
100
is
considered
adequate
for
acute
exposure
via
inhalation
and
for
short­
and
intermediate­
term
incidental
ingestion
exposures.
A
target
MOE
of
300
is
considered
adequate
for
short­
and
intermediate­
term
inhalation
exposures.
Mosquito
abatement
postapplication
and
indoor
aerosol
space
spray
application
scenarios
are
assessed
as
acute
exposures.
All
other
residential
handler
and
post­
application
exposure
scenarios
are
assessed
as
short­
and
intermediate­
term
exposures.
Exposure
and
risk
estimates
for
each
scenario
are
summarized
below
and
a
more
detailed
summary
of
risk
calculations,
critical
assumptions,
and
results
is
provided
in
Tables
13­
21
on
pages
53­
56
of
this
document.

The
results
of
the
residential
exposure
assessment
indicate
that
with
one
exception,
all
residential
exposure
scenarios
assessed
based
on
master
label
specified
uses
result
in
MOEs
greater
than
the
applicable
target
MOEs
i.
e.,
all
but
one
result
in
exposures
below
the
level
of
concern.
The
short­
term
residential
bystander
inhalation
risk
from
outdoor
automatic
misters
is
the
only
scenario
of
concern.
Bystander
inhalation
risk
for
toddlers
is
of
concern
when
exposure
is
to
the
piperonyl
butoxide
air
concentration
resulting
from
2,
1­
minute
spray
durations
(
MOE
Toddlers
=
190).
When
exposure
is
to
2,
30­
second
spray
durations,
risk
is
not
of
concern
(
MOE
Toddlers
=
370).

6.0
AGGREGATE
RISK
ASSESSMENT
AND
RISK
CHARACTERIZATION
The
aggregate
risk
assessment
integrates
the
assessments
conducted
for
dietary,
drinking
water,
and
residential
exposure.
Since
there
is
potential
for
concurrent
exposure
via
the
food,
water
and
residential
pathways,
the
combined
exposures
are
estimated
using
the
methodology
described
below
and
are
compared
with
modeling­
based
estimates
of
drinking
water
contamination
determined
by
EFED.
Page
40
of
61
For
the
aggregate
exposure
assessment,
DWLOCs
were
calculated
and
compared
with
the
estimated
drinking
water
concentrations
of
piperonyl
butoxide
in
ground
water
and
surface
water.
The
DWLOC
is
the
concentration
of
a
chemical
in
drinking
water
that
would
be
acceptable
as
an
upper
limit
in
light
of
total
aggregate
exposure
to
that
chemical
from
food,
water,
and
residential
sources.
The
acute
and
chronic
DWLOCs
for
piperonyl
butoxide
consider
aggregate
exposure
from
food
and
water
only.
The
short­
term
DWLOC
aggregates
exposures
from
food,
water
and
residential
routes
associated
with
application
of
piperonyl
butoxide
and
is
calculated
only
if
there
is
a
common
toxicity
endpoint
for
each
route
of
exposure.

6.1
Acute
Aggregate
Risk
Assessment
Acute
DWLOCs
were
calculated
based
on
acute
dietary
exposure
estimates
and
default
body
weights
and
water
consumption
figures.
The
Agency's
default
body
weight/
water
consumption
assumptions
are
70
kg/
2
L
(
adult
male),
60
kg/
2
L
(
youth
13­
19
and
adult
female)
and
10
kg/
1
L
(
infants
and
children
<
12
years).
To
calculate
the
DWLOC,
the
acute
dietary
food
exposure
is
subtracted
from
the
aPAD.
Acute
DWLOCs
and
EDWCs
are
provided
in
Table
10.

Table
10.
Piperonyl
Butoxide
­
Drinking
Water
Levels
of
Comparison
for
Acute
Dietary
Exposure
Population
Subgroup
Acute
PAD
(
mg/
kg/
day)
Food
Exposure
(
mg/
kg/
day)
99.9th
percentile
Acute
Water
Exposure
(
mg/
kg/
day)
DWLOC
acute*
(
ug/
L)
Surface
Water
EDWC
(
ug/
L)
Ground
Water
EDWC
(
ug/
L)

US
Population
6.3
0.38
6
210000
240
0.26
All
Infants
0.39
6
59000
240
0.26
Children
1­
2
1.23
5
51000
240
0.26
Children
3­
5
0.80
5.5
55000
240
0.26
Children
6­
12
0.41
6
59000
240
0.26
Youths
13­
19
0.35
6
180000
240
0.26
Adults
20­
49
0.30
6
210000
240
0.26
Females
13­
49
0.35
6
180000
240
0.26
Adults
50+
0.29
6
210000
240
0.26
*
DWLOCacute
=
[
acute
water
exposure
(
mg/
kg/
day)
x
(
body
weight)]
[
consumption
(
L)
x
10­
3
mg/
µ
g]
where,
acute
water
exposure
(
mg/
kg/
day)
=
[
aPAD
­
(
acute
food
(
mg/
kg/
day)]

The
EDWCs
for
both
surface
water
and
groundwater
are
well
below
the
acute
DWLOCs
for
the
general
U.
S.
population
and
all
other
population
subgroups
indicating
that
acute
aggregate
exposure
to
piperonyl
butoxide
in
food
and
water
is
less
than
HED's
level
of
concern
for
these
populations.

6.2
Short­
Term
Aggregate
Risk
Assessment
The
short
term
aggregate
risk
is
the
estimated
risk
associated
with
aggregated
risks
from
Page
41
of
61
average
food
exposures,
average
drinking
water
exposures,
and
short­
term
oral,
dermal
and
inhalation
exposures.
The
toxicity
endpoints
selected
for
the
dietary,
drinking
water
,
and
incidental
oral
routes
of
exposure
may
be
aggregated
because
of
the
common
toxicity
endpoints
(
decreased
body
weight
gain)
via
these
routes.
Inhalation
exposures
are
not
included
in
the
short­
term
aggregate
risk
estimate
because
the
toxicity
endpoints
selected
for
the
chronic
dietary/
drinking
water
routes
of
exposure
and
those
selected
for
inhalation
route
of
exposure
are
not
based
on
common
effects
i.
e.,
the
chronic
dietary
endpoint
is
based
decreased
body
weight
gain
and
liver
effects
and
the
short­
term
inhalation
endpoint
is
based
on
laryngeal
hyperplasia
and
metaplasia.
The
short
term
aggregate
risk
for
piperonyl
butoxide
is
calculated
by
adding
exposure
estimates
from
dietary,
drinking
water,
and
incidental
oral
exposure
pathways
for
children
age
1­
2
and
comparing
them
with
model
based
EDWCs
determined
by
EFED.
The
calculated
short­
term
DWLOC
and
EDWCs
are
presented
in
Table
11.

Table
11.
Piperonyl
Butoxide
­
Short­
Term
Aggregate
Risk
and
DWLOC
Calculations
Population
Target
Aggregate
MOE1
MOE
food2
MOE
Incidental
Oral3
Aggregate
MOE
(
food
&
residential)
4
MOE
water5
Allowable
water
exposure6
(
mg/
kg/
day)
Ground
Water
EDWC
(
ug/
L)
Surface
Water
EDWC
(
ug/
L)
DWLOC7
(
ug/
L)

Child
1­
2
100
4800
4700
2400
100
0.85
0.26
60
8500
1
Target
MOE
based
on
UF
of
10
for
intraspecies
variation
and
10
for
intraspecies
extrapolation
2
MOE
food
=
[(
short/
intermediate­
term
incidental
oral
NOAEL
=
89
mg/
kg/
day)/(
chronic
dietary
exposure
=
0.0185
mg/
kg/
day)]
3
MOE
incidental
oral
=
[(
short
or
intermediate­
term
oral
NOAEL
=
89
mg/
kg/
day)/(
incidental
oral
residential
exposure
=
0.019
mg/
kg/
day)];
4
Aggregate
MOE
(
food
and
residential)
=
1
÷
[(
1
÷
MOE
food)
+
(
1
÷
MOE
incidental
oral)]
5
Water
MOE
=
1
÷
[(
1
÷
Target
Aggregate
MOE)
­
(
1
÷
Aggregate
MOE
(
food
and
residential)]
6
Allowable
water
exposure
=
Short
or
Intermediate
Term
Oral
NOAEL
÷
MOE
water
7
DWLOC
(
ug/
L)
=
[
allowable
water
exposure
(
mg/
kg/
day)
x
body
weight
(
kg)]
BW
=
10
kg
[
water
consumption
(
L)
x
10­
3
mg/
ug]
Daily
Water
Consumption
=
1L
EFED's
model
based
estimates
for
average
concentrations
of
piperonyl
butoxide
in
surface
and
ground
water
are
60
and
0.26
ppb
respectively.
The
short
term
DWLOC
for
children
1­
2
years
old
is
8500
µ
g/
L.
Since
the
model­
based
estimates
for
allowable
concentrations
in
surface
water
and
groundwater
are
below
the
calculated
short
term
DWLOC,
HED
concludes
that
aggregate
exposure
to
food
and
drinking
water
will
not
result
in
an
unacceptable
risk.

6.3
Chronic
Aggregate
Risk
Assessment/
DWLOCs
Chronic
DWLOCs
were
calculated
based
on
the
chronic
dietary
exposure
estimates
and
default
body
weights
and
water
consumption
figures.
Calculated
chronic
DWLOCs
and
EDWCs
are
provided
in
Table
11.
To
calculate
the
chronic
DWLOC,
the
chronic
dietary
food
exposure
is
subtracted
from
the
chronic
PAD.

Table
12.
Drinking
Water
Levels
of
Comparison
for
Chronic
Dietary
Exposure
Population
Subgroup
Chronic
PAD
(
mg/
kg/
day)
Food
Exposure
(
mg/
kg/
day)
Max.
Water
Exposure
(
mg/
kg/
day)
DWLOC
(
ug/
L)
Surface
Water
Annual
Avg
EDWC
(
ug/
L)
Ground
Water
Annual
Avg
EDWC
(
ug/
L)

US
Population
0.155
0.0078
0.15
5200
60
0.26
Table
12.
Drinking
Water
Levels
of
Comparison
for
Chronic
Dietary
Exposure
Population
Subgroup
Chronic
PAD
(
mg/
kg/
day)
Food
Exposure
(
mg/
kg/
day)
Max.
Water
Exposure
(
mg/
kg/
day)
DWLOC
(
ug/
L)
Surface
Water
Annual
Avg
EDWC
(
ug/
L)
Ground
Water
Annual
Avg
EDWC
(
ug/
L)

Page
42
of
61
All
Infants
(<
1
year)
0.155
0.0057
0.15
1500
60
0.26
Children
1­
2
years
0.155
0.0185
0.14
1400
60
0.26
Children
3­
5
years
0.155
0.0169
0.14
1400
60
0.26
Children
6­
12
years
0.155
0.0130
0.14
1400
60
0.26
Youth
13­
19
years
0.155
0.0062
0.15
4500
60
0.26
Adults
20­
49
years
0.155
0.0064
0.15
5200
60
0.26
Females
13­
49
years
0.155
0.0070
0.15
4500
60
0.26
Adults
50+
0.155
0.0066
0.15
5200
60
0.26
DWLOCchronic
=
[
chronic
water
exposure
(
mg/
kg/
day)
x
(
body
weight)]
[
consumption
(
L)
x
10­
3
mg/
µ
g]
where,
chronic
water
exposure
(
mg/
kg/
day)
=
[
cPAD
­
(
chronic
food
(
mg/
kg/
day)]

The
average
EDWCs
for
both
surface
water
(
60
ug/
L)
and
groundwater
(
0.26
ug/
L)
are
less
than
the
chronic
DWLOCs,
indicating
that
chronic
exposure
to
piperonyl
butoxide
in
food
and
water
is
less
than
HED's
level
of
concern.

7.0
CUMULATIVE
RISK
Section
408(
b)(
2)(
D)(
v)
of
FFDCA
requires
that,
when
considering
whether
to
establish,
modify,
or
revoke
a
tolerance,
the
Agency
consider
"
available
information"
concerning
the
cumulative
effects
of
a
particular
pesticide's
residues
and
"
other
substances
that
have
a
common
mechanism
of
toxicity."

EPA
does
not
have,
at
this
time,
available
data
to
determine
whether
piperonyl
butoxide
has
a
common
mechanism
of
toxicity
with
other
substances.
Unlike
other
pesticides
for
which
EPA
has
followed
a
cumulative
risk
approach
based
on
a
common
mechanism
of
toxicity,
EPA
has
not
made
a
common
mechanism
of
toxicity
finding
as
to
piperonyl
butoxide
and
any
other
substances
and,
piperonyl
butoxide
does
not
appear
to
produce
a
toxic
metabolite
produced
by
other
substances
which
have
tolerances
in
the
U.
S.
For
the
purposes
of
this
tolerance
reassessment
action,
therefore,
EPA
has
not
assumed
that
piperonyl
butoxide
has
a
common
mechanism
of
toxicity
with
other
substances.
For
information
regarding
EPA's
efforts
to
determine
which
chemicals
have
a
common
mechanism
of
toxicity
and
to
evaluate
the
cumulative
effects
of
such
chemicals,
see
the
policy
statements
released
by
EPA's
OPP
concerning
common
mechanism
determinations
and
procedures
for
cumulating
effects
from
substances
found
to
have
a
common
mechanism
on
EPA's
website
at
http://
www.
epa.
gov/
fedrgstr/
EPA­
PEST/
2002/
January/
Day­
16/.

8.0
OCCUPATIONAL
EXPOSURE
AND
RISK
Page
43
of
61
Based
on
the
Master
Label,
31
occupational
exposure
scenarios
have
been
assessed
for
this
RED.
Only
inhalation
exposures
have
been
assessed
for
each
of
the
occupational
scenarios.
Dermal
exposures
were
not
assessed
because
no
dose
or
endpoints
were
selected
for
dermal
exposure.
Short,
intermediate,
and
long­
term
exposures
are
expected/
assessed
for
occupational
exposure
scenarios
based
on
use
patterns.
Agricultural
handler
exposures
are
assessed
as
shortand
intermediate­
term.
Pesticide
control
operator
exposures
are
assessed
as
short­,
intermediateand
long­
term.
Mosquito
abatement
exposures
are
assessed
as
short­
and
intermediate­
term
for
aerial
and
backpack
spray
applications
and
short­,
intermediate­,
and
long­
term
for
truck
mounted
ULV
spray
applications.
(
B.
Daiss,
D313107,
3/
xx/
04)

8.1
Occupational
Exposure
Scenarios
Only
occupational
handler
scenarios
were
assessed
for
the
piperonyl
butoxide
RED.
The
term
"
handler"
applies
to
individuals
who
mix,
load,
and
apply
the
pesticide
product.
Occupational
post­
application
scenarios
were
not
assessed
because
there
is
no
endpoint
for
the
dermal
exposure,
the
only
relevant
route
of
concern
for
post­
application
worker
exposure.
Based
primarily
on
information
provided
in
the
Master
Label
regarding
current
registrant
supported
uses,
HED
assessed
the
following
scenarios
for
agricultural,
professional
pest
control
operator,
and
mosquito
control
applications
for
the
piperonyl
butoxide
RED.
Application
of
dust
with
shaker
can,
bulb
duster
and
power
duster,
a
relevant
and
potentially
significant
exposure
scenario
was
not
assessed
due
to
lack
of
dust­
specific
or
adequate
surrogate
data
on
inhalation
exposure
associated
with
this
activity.

8.1.1
Agricultural
Handler
Scenarios
1)
mixing
and
loading
liquids
for
aerial
and/
or
chemigation
application
to
field
crops
2)
mixing
and
loading
liquids
for
groundboom
application
to
field
crops
3)
mixing
and
loading
liquids
for
airblast
application
to
field
crops
4)
mixing
and
loading
wettable
powders
for
aerial
and/
or
chemigation
application
to
field
crops
5)
mixing
and
loading
wettable
powders
for
groundboom
application
to
field
crops
6)
mixing
and
loading
wettable
powders
for
airblast
application
to
field
crops
7)
applying
liquids
aerially
to
field
crops
8)
applying
liquids
with
ground
boom
sprayer
to
field
crops
9)
applying
liquids
with
airblast
sprayer
to
field
crops
10)
mixing,
loading
and
applying
liquids
with
high
pressure
hand
wand
for
greenhouse
application
11)
mixing,
loading
and
applying
liquids
with
backpack
sprayer
or
low
pressure
handwand
for
greenhouse
application
12)
mixing
loading
and
applying
wettable
powder
with
backpack
sprayer
or
low
pressure
hand
wand
for
greenhouse
application
13)
mixing,
loading
and
applying
liquids
with
backpack
sprayer
or
low
pressure
hand
wand
for
Page
44
of
61
agricultural
premise
and
equipment
application
14)
flagging
for
aerial
spray
application
8.1.2
Pesticide
Control
Operator
Handler
Scenarios
1)
mixing,
loading
and
applying
liquids
indoors
for
surface
spray
application
with
low
pressure
handwand;
2)
mixing,
loading
and
applying
liquids
indoors
for
crack
and
crevice
application
with
low
pressure
handwand;
3)
mixing,
loading
and
applying
wettable
powders
indoors
for
surface
spray
application
with
low
pressure
handwand;
4)
mixing,
loading
and
applying
wettable
powders
indoors
for
crack
and
crevice
application
with
low
pressure
handwand;
5)
mixing,
loading
and
applying
liquids
with
backpack
sprayer
or
low
pressure
hand
wand
for
general
outdoor
sites;
6)
mixing,
loading
and
applying
liquids
for
hand
gun
sprayer
application
to
lawns;
7)
mixing,
loading
and
applying
liquids
for
groundboom
application
to
golf
courses
8)
mixing,
loading
and
applying
liquids
for
back
pack
sprayer
or
low
pressure
handwand
application
to
stored
grain
9)
mixing,
loading
and
applying
liquids
for
high
pressure
handwand
application
to
stored
grain
1)
mixing,
loading
and
applying
liquids
for
low
pressure
handwand
application
to
warehouse
stored
produce
11)
applying
liquids
to
golf
courses
with
groundboom
sprayer
12)
aerosol
spray
application
indoors
13)
mixing
and
loading
liquid
formulations
for
the
systems'
holding
tanks
for
outdoor
automatic
mister
systems
8.1.3
Mosquito
Abatement
Scenarios
1)
mixing,
loading
liquids
for
aerial
application
2)
mixing,
loading
liquids
for
ULV
truck
mounted
spray
application
3)
mixing,
loading,
applying
liquids
with
truck
mounted
ULV
ground
spray
(
airblast
sprayer
unit
exposure
used
as
surrogate)
4)
mixing,
loading,
applying
liquids
with
back
pack
sprayer
8.1.4
Direct
Application
to
Pets
and
Farm
Animals
(
by
veterinarians
and
groomers)

C
spray
application
Page
45
of
61
8.2
Occupational
Exposure
Data
and
Assumptions
8.2.1
Exposure
Data
8.2.1.1
Application
Parameters
Application
rates
for
all
of
the
occupational
exposure
scenarios
assessed
are
based
on
information
provided
in
the
Piperonyl
Butoxide
Master
Label
which
lists
all
of
the
uses
that
Piperonyl
Butoxide
Task
Force
II
members
are
supporting.
Therefore,
it
is
important
all
labels
be
revised
to
reflect
the
supported
uses
and
maximum
allowable
application
rates
provided
in
the
Master
Label.

8.2.1.2
Handler
Exposure
Data
Data
from
the
PHED
or
ORETF
data
bases
were
used
to
assess
occupational
handler
exposures.
Default
application
assumptions
regarding
areas
treated
or
amounts
applied
for
agriculture
and
mosquito
abatement
handler
exposure
scenarios
are
documented
in
the
HED
Science
Advisory
Committee
on
Exposure's
SOP
9,
"
Standard
Values
for
Daily
Acres
Treated
in
Agriculture"
(
7/
5/
2000).
Information
on
how
pest
control
operators
use
pesticide
products
was
obtained
from
a
survey
conducted
by
the
National
Pest
Management
Association
(
NPMA).
NPMA
sponsored
a
"
Pest
Control
Operators
(
PCO)
Product
Use
and
Usage
Information
Survey".

8.2.2
Exposure
Assumptions
The
following
assumptions
were
used
in
estimating
risks
to
occupational
handlers
from
exposure
to
piperonyl
butoxide:

°
Average
body
weight
of
an
adult
handler
is
70
kg
°
Exposure
duration
is
short­
term
and
intermediate
term
for
agricultural
handlers
and
short­,
intermediate­
and
long­
term
for
PCOs
and
mosquito
control
applicators
°
Baseline
inhalation
exposure
(
no
respiratory
protection)
°
Maximum
application
rates
as
provided
by
Piperonyl
Butoxide
Task
Force
II
were
used
for
all
types
and
methods
of
application;
rates
used
for
exposure
assessment
are
provided
in
Table
3
of
the
Occupational
Exposure
Assessment
(
B.
Daiss,
D310033,
11/
04)
Outdoor
automatic
mister
systems
­
application
rate
(
lb
ai/
gal
soln)
used
is
from
a
product
label
assumed
to
represent
typical
automatic
mister
systems
(
M.
Crowley,
D315334,
8/
05)
°
Maximum
daily
volumes
handled
and/
or
area
treated
used
for
the
scenarios
assessed
are
as
follows
­
aerial
applications
@
350
acres
per
day
for
typical
acreage
field
crops;
1200
for
high
acreage
field
crops
(
e.
g.,
corn,
rice,
wheat)

@
7500
acres
per
day
for
mosquito
control
adulticide
applications
­
groundboom
applications
Page
46
of
61
@
80
acres
treated
per
day
for
field
crops
@
40
acres
treated
per
day
for
golf
course
turf
­
airblast
applications
­
40
acres
treated
per
day
for
agricultural
applications;
­
ULV
truck
mounted
sprayer
­
3000
acres
treated
per
day
for
mosquito
control
(
airblast
used
as
surrogate)
­
pet
groomer/
veterinary
applications
@
8
pet
animals
are
treated
per
day
@
one
half
of
a
16
oz
spray
container
used
to
treat
each
animal
­
high
pressure
handwand
application
­
10
acres
treated
or
1000
gallons
of
spray
solution
used
per
day
­
backpack
sprayer
or
a
low
pressure
handwand
sprayer
applications
@
2
acres
treated
or
40
gallons
spray
solution
used
per
day
for
agricultural
premise/
mosquito
control/
general
outdoor
site
applications
@
5
grain
storage
bins
treated
per
day
with
cross­
sectional
area
of
1000
square
feet
per
bin
@
5
food
produce
storage
warehouses
treated
per
day,
area
treated
per
warehouse
is
10,000
square
feet
­
pest
control
operator
applications
@
a
maximum
of
7
commercial
buildings
or
residential
homes
treated
per
day
for
general
pest
control
management
activities
@
average
area
treated
per
building
is
1600
square
feet
for
surface
spray
and
crack
and
crevice
treatment
and
12800
cubic
feet
for
space
spray
application
(
EPA
Exposure
Factors
Handbook)

@
for
outdoor
automatic
mister
systems,
holding
tank
size
is
55
gallons
and
250
gallons
based
on
information
provided
to
SRRD
from
the
registrants;
handlers
(
i.
e.,
system
maintenance
workers)
are
assumed
to
fill
5
holding
tanks
per
day
Non­
Standard
Exposure
Assumptions
°
Assumptions
used
for
veterinary
and
grain
storage
treatments
are
not
included
in
the
Occupational
Exposure
SOPs
but
represent
values
that
have
been
used
by
the
Agency
in
previous
assessments
(
e.
g.,
carbaryl,
cyfluthrin).
°
Assumptions
used
for
daily
area
treated
for
produce
storage
warehouses
are
based
on
best
professional
judgement.
°
Assumptions
used
for
general
pest
control
applicators
are
based
data
from
the
NPMA
survey.
Based
on
BEAD's
review
of
the
NPMA
survey,
PCOs
conducting
general
pest
control
activities
would
treat
an
average
of
between
6
and
7
buildings
per
day,
assuming
an
8­
hour
work
day.
°
Airblast
application
unit
exposure
data
was
used
to
assess
exposure
resulting
from
truck
mounted
ULV
application
of
mosquito
adulticide.
In
the
absence
of
more
equipment
specific
data,
airblast
unit
exposure
data
is
thought
to
provide
reasonable
surrogate
exposure
information
based
on
the
similarity
of
the
two
application
methods
and
has
been
used
for
this
purpose
in
previous
HED
occupational
exposure
assessments
(
e.
g.,
carbaryl).
Page
47
of
61
°
Specific
reference
to
"
automatic
mister
systems"
is
not
made
in
the
Piperonyl
Butoxide
Master
Label
however
there
is
reference
to
use
of
PBO
in
outdoor
domestic
sites
as
a
general,
crack­
and­
crevice,
or
spot
surface
spray.
Four
PBO­
containing
products
(
EPA
Reg.
No.
1021­
1785,
21165­
24,1021­
1800,
and
655­
797)
identified
in
a
Consumer
Specialty
Products
Association
(
CSPA)
discussion
paper
(
CSPA,
2005),
reference
specific
nozzle
spray
systems
used
in
outdoor
residential
sites.
The
following
is
additional
general
use
information
from
the
CSPA
discussion
paper:
holding
tanks
or
reservoirs
are
typically
plastic
with
30,
55,
or
250
gallon
capacity;
nozzle
height
is
approximately
8
 
10
feet
(
i.
e.,
off
the
ground);
nozzle
spacing
is
approximately
10
 
15
feet
apart
along
fences
or
foliage
(
i.
e.,
perimeter
separation);
automatic
dispersions
are
set
for
2
to
4
times
per
day
for
30
to
60
seconds
per
event;
systems
can
be
activated
manually
by
homeowners.

8.3
Occupational
Exposure
and
Risk
Estimates
A
target
MOE
of
300
for
the
inhalation
route
is
considered
adequate
for
short­
and
intermediate­
term
occupational
exposure
and
risk.
A
target
MOE
of
1000
is
considered
adequate
for
long­
term
worker
exposure
via
the
inhalation
route.
Agricultural
handler
exposures
are
assessed
as
short­
and
intermediate­
term.
Pesticide
control
operator
exposures
are
assessed
as
short­,
intermediate­
and
long­
term.
Mosquito
abatement
worker
exposures
are
assessed
as
shortand
intermediate­
term
for
aerial
and
backpack
spray
applications
and
short­,
intermediate­,
and
long­
term
for
truck
mounted
ULV
spray
applications.
Exposure
and
risk
estimates
for
each
scenario
are
summarized
below
and
a
more
detailed
summary
of
exposure
and
risk
calculations,
critical
assumptions,
and
results
is
provided
in
Tables
22­
26
on
pages
56­
61
of
this
document.

The
results
of
the
worker
exposure
assessment
indicate
that
the
following
agricultural
application
exposure
scenarios
result
in
MOEs
less
than
the
target
MOE
of
300
for
inhalation
for
short­
and
intermediate­
term
exposure.

­
Mixing
and
loading
wettable
powders
for
aerial
and/
or
chemigation
application
to
field
crops.
The
MOE
at
the
maximum
application
rate
of
0.5
lb
ai/
acre
for
typical
acreage
field
crops
is
s
40;
the
MOE
for
high
acreage
field
crops
is
11.
MOEs
greater
than
the
target
MOE
of
300
result
at
an
application
rate
of
0.06
lb
ai/
acre
for
the
typical
acreage
field
crop
scenario
and
0.018
lb
ai/
acre
for
the
high
acreage
scenario.

­
Mixing
and
loading
wettable
powders
for
groundboom
application
to
field
crops.
The
MOE
at
the
maximum
application
rate
of
0.5
lb
ai/
acre
is
160.
MOEs
greater
than
the
target
MOE
of
300
MOEs
result
at
an
application
rate
of
0.25
lb
ai/
acre
for
this
scenario.

­
Mixing,
loading
and
applying
liquids
for
high
pressure
handwand
application
to
greenhouse
crops.
The
MOE
at
the
maximum
application
rate
of
1.5
lb
ai/
acre
is
160.
MOEs
greater
than
the
target
MOE
of
300
result
at
an
application
rate
of
0.7
lb
ai/
acre
for
this
scenario.
Page
48
of
61
­
Mixing,
loading
and
applying
wettable
powders
for
low
pressure
handwand
application
to
greenhouse
crops.
The
MOE
at
the
maximum
application
rate
of
1.5
lb
ai/
acre
is
85.
MOEs
greater
than
the
target
MOE
of
300
result
at
an
application
rate
of
0.4
lb
ai/
acre
for
this
scenario.

The
results
of
the
worker
exposure
assessment
indicate
that
the
following
pest
control
operator
application
exposure
scenarios
result
in
MOEs
less
than
the
target
MOE
of
1000
for
long­
term
exposure.

­
Mixing,
loading
and
applying
liquids
for
low
pressure
handwand
application
for
crack
and
crevice
treatment.
The
MOE
at
the
maximum
application
rate
of
2.2
lb
ai/
1000
ft2
and
7
buildings
treated
per
day
is
380.
MOEs
greater
than
the
target
MOE
of
1000
result
at
the
maximum
application
rate
of
2.2
lb
ai/
1000
ft2
if
the
number
of
buildings
treated
per
day
is
reduced
to
one,
or
if
the
application
rate
is
reduced
to
0.3
ai/
1000
ft2
for
7
buildings
treated
per
day.

­
Mixing,
loading
and
applying
wettable
powders
for
low
pressure
handwand
application
for
indoor
surface
spray
treatment.
The
MOE
at
the
maximum
application
rate
of
0.56
lb
ai/
1000
ft2
and
7
buildings
treated
per
day
is
40.
MOEs
greater
than
the
target
MOE
of
1000
result
if
the
application
rate
is
reduced
to
of
0.16
lb
ai/
1000
ft2
and
only
1
building
is
treated
per
day.

­
Mixing,
loading
and
applying
wettable
powders
for
low
pressure
handwand
application
for
crack
and
crevice
treatment.
The
MOE
at
the
maximum
application
rate
of
2.2
lb
ai/
1000
ft2
and
7
buildings
treated
per
day
is
10.
MOEs
greater
than
the
target
MOE
of
1000
result
if
the
application
rate
is
reduced
to
of
0.16
lb
ai/
1000
ft2
and
only
1
building
is
treated
per
day.

­
Applying
aerosols
for
indoor
space
spray
application.
The
MOE
at
the
likely
maximum
application
rate
of
0.025
lb
ai
per
16
oz.
can
with
two
cans
applied
per
building
and
7
buildings
treated
per
day
is
615.
MOEs
greater
than
the
target
MOE
of
1000
result
if
the
application
rate
is
reduced
to
0.012
lb
ai
per
16
oz
can.

The
results
of
the
worker
exposure
assessment
indicate
that
the
following
mosquito
abatement
application
exposure
scenario
results
in
an
MOE
less
than
the
target
MOE
of
1000
for
long­
term
exposure.

­
Mixing
and
loading
liquids
for
aerial
spray
application.
The
MOE
at
the
maximum
application
rate
of
0.08
lb
ai/
acre
is
390
if
an
open
cab
is
assumed.
MOEs
greater
than
the
target
MOE
of
1000
result
if
the
maximum
application
rate
is
reduced
to
0.03
0.08
lb
ai/
acre.

­
Mixing,
loading
and
applying
liquids
for
ULV
truck
mounted
spray
application.
The
MOE
at
the
maximum
application
rate
of
0.08
lb
ai/
acre
is
260
if
an
open
cab
is
assumed.
MOEs
greater
than
the
target
MOE
of
1000
result
at
the
maximum
application
rate
if
a
closed
cab
is
assumed.
Page
49
of
61
All
other
occupational
exposure
scenarios
assessed
based
on
master
label
specified
uses
result
in
MOEs
greater
than
the
applicable
target
MOEs.

9.0
INCIDENT
REPORT
Based
on
data
from
Poison
Control
Centers,
there
appears
to
be
a
greater
risk
of
moderate
or
major
symptoms
among
those
exposed
to
products
containing
pyrethrins
and
piperonyl
butoxide
than
those
exposed
to
pyrethrins
alone.
A
detailed
review
of
symptoms
found
that
respiratory
symptoms
(
bronchospasm,
cough/
choke,
and
dyspnea)
and
selected
dermal
symptoms
(
dermal
irritation/
pain,
itching,
and
rash)
were
more
likely
if
the
exposure
included
piperonyl
butoxide.
These
symptoms
are
likely
the
reason
for
increased
risk
of
moderate
effects
which
typically
would
require
medical
attention.
Other
literature
suggests
that
pyrethrin­
based
products
may
pose
a
hazard
to
asthmatics.
The
findings
from
analysis
of
symptoms
from
Poison
Control
Centers
suggests
that
piperonyl
butoxide
adds
to
that
risk.

Based
on
these
findings,
it
is
recommended
that
labeling
advise
handlers
using
products
containing
piperonyl
butoxide
as
follows:
Avoid
contact
with
skin
or
eyes.
Susceptible
individuals
may
experience
irritant
or
allergic­
type
reactions.
Persons
with
respiratory
illness
may
experience
difficulty
breathing
and
should
avoid
use
in
enclosed
spaces
and
consult
their
physician
prior
to
use.
(
Review
of
Pyrethrins
Incident
Reports
­
Second
Revision,
J.
Blondell,
D320300,
8/
16/
04)

10.0
UNCERTAINTIES
AND
RISK
CHARACTERIZATION
The
dietary
exposure
analyses
conservatively
assume
use
of
maximum
application
rates.
The
highly
refined
acute
and
chronic
dietary
exposure
assessment
for
piperonyl
butoxide
could
be
refined
further
by
additional
residue
data
on
the
level
of
metabolites
and
parent
in
cereal
grains
and
beans/
peas
where
the
ratio
of
2
as
recommended
by
the
HED
MARC
was
used.
In
addition,
monitoring
data
or
field
trial
residues
for
field
corn,
sweet
corn,
and
cottonseed
could
further
refine
the
assessment.

The
drinking
water
assessment
focuses
on
the
terrestrial
agricultural
uses
of
piperonyl
butoxide
since
they
are
considered
more
likely
to
contaminate
drinking
water
sources.
The
cranberry,
mosquito
adulticide
and
carp
bait
uses
are
not
considered,
although
each
has
the
potential
to
contaminate
water,
because
EFED
does
not
have
standard
methods
for
estimating
drinking
water
contamination
from
these
use
patterns.

Inhalation
risk
estimates
are
conservatively
based
on
a
local
or
portal
of
entry
effect
(
i.
e.,
laryngeal
hyperplasia
and
metaplasia).
The
NOAEL
for
systemic
inhalation
effects
is
30
times
higher
than
the
endpoint
selected
based
on
local
effects.

Initial
exposure
estimates
for
the
occupational
and
residential
assessment
are
conservatively
based
use
of
maximum
application
rates
provided
in
the
master
label.
It
was
also
assumed,
based
on
the
master
label,
that
products
for
all
applications
are
supported/
available
in
multiple
forms
i.
e.,
Page
50
of
61
liquids,
dust,
wettable
powders.
However,
given
that
the
majority
of
piperonyl
butoxide
products
are
available
as
liquid
formulations,
scenarios
involving
handling
and
application
of
liquid
formulations
are
likely
to
be
more
representative
of
actual
exposure.

The
SOP
default
occupational
and
residential
unit
exposures
selected
for
each
scenario
were
based
on
central­
tendency
values
from
PHED.
The
mean
exposure
data
from
the
NDETF
study
used
to
estimate
exposures
from
indoor
fogger
release
is
comprehensive
and
should
accurately
represent
likely
exposures
from
total
release
foggers.

Uncertainties
identified
by
BEAD
regarding
the
NPMA
survey
data
used
to
determine
potential
exposures
to
PCOs
should
also
be
noted.
Regarding
the
robustness
and
validity
of
the
NPMA
survey
data
BEAD
drew
the
following
conclusions.
Given
that
there
are
approximately
19,000
PCO
firms
in
the
U.
S.,
it
is
highly
unlikely
that
a
sample
size
of
67
represents
a
statistically
valid
sample.
The
use
of
a
retrospective
survey
methodology
may
have
introduced
errors
in
the
data.
Pesticide
survey
firms
like
Doane
use
a
prospective
survey
instrument
sent
to
growers
in
advance
thus
allowing
them
to
keep
detailed
accounts
of
their
pesticide
usage
in
real
time
throughout
the
year.
Despite
its
small
size
and
retrospective
methodology,
however,
the
information
collected
is
more
robust
than
BEAD
typically
gets
when
asking
questions
of
this
nature.
BEAD
typically
contacts
1­
5
PCO's
and
asks
chemical
specific
questions
which
may
bias
the
responses
if
PCO's
value
the
chemical
under
review.
(
D.
Brassard,
D305276,
7/
04)
HED
believes
the
NPMA
survey
provides
reasonable
estimates
of
average
number
of
buildings
treated
per
day
by
PCOs.

For
pest
control
operator
and
mosquito
abatement
scenarios,
assuming
full
day,
long
term
application
for
each
application
method
may
significantly
overestimate
total
exposure.
Based
on
data
on
usage
of
likely
piperonyl
butoxide
containing
pesticides
presented
in
the
NPMA
survey,
this
assumption
would
result
in
significant
overestimate
of
exposure
for
PCOs.
Similarly,
assuming
continuous
usage
of
piperonyl
butoxide
containing
pesticides
for
mosquito
abatement
applications
would
also
significantly
overestimate
total
exposure
based
on
personal
communication
with
mosquito
control
district
officials
regarding
current
usage
of
these
products.
However,
piperonyl
butoxide
is
used
to
control
a
large
number
and
a
wide
variety
of
pests
and
labels
do
not
restrict
or
preclude
repeated
applications
or
long
term
use.
Given
the
potential
for
multiple
applications
and
long­
term
use
for
occupational
handlers,
inclusion
of
a
repeated
use/
long­
term
exposure
scenario
for
pest
control
operators
and
mosquito
abatement
is
considered
reasonable.

Application
of
dust
with
shaker
can,
bulb
duster
and
power
duster,
a
relevant
and
potentially
significant
exposure
scenario
for
both
residential
and
occupational
exposures,
was
not
assessed
due
to
lack
of
dust­
specific
or
adequate
surrogate
data
on
inhalation
exposure
associated
with
this
activity.
Use
of
existing
applicator
data
for
surrogate
exposure
assumptions
for
this
exposure
scenario
would
likely
underestimate
potential
risk
HED
did
not
conduct
a
quantitative
assessment
of
potential
exposure
from
indoor
misters
due
to
data
limitations.
However,
HED
recommends
that
the
use
restrictions,
both
general
and
Page
51
of
61
specific,
prescribed
by
the
master
label
be
required
for
all
labels
for
indoor
misters
that
contain
PBO.
These
restrictions
include
the
following:
general
use
restrictions
­
do
not
apply
when
other
persons
are
present,
do
not
apply
when
pets
(
except
fish)
are
present,
remove
or
cover
exposed
food
and
water
before
application,
remove
or
cover
dishes,
utensils,
food
processing
equipment,
and
food
preparation
surfaces
or
wash
them
thoroughly
before
use,
do
not
breathe
dust,
vapors,
or
spray
mist;
specific
metered
release
application
use
restrictions
­
do
not
use
in
nurseries
or
rooms
where
infants,
ill
or
aged
persons
are
confined,
do
not
place
metering
device
directly
over
or
within
8
feet
of
exposed
foods,
dishes,
utensils,
food
processing
equipment,
and
food
handling
or
prepartion
areas.
It
should
be
noted
that
a
screening
assessment
of
indoor
misters
was
conducted
for
the
pyrethrin
risk
assessment.
HED
believes
the
pyrethrin
assessment
provides
support
for
the
label
restrictions
listed
above
for
indoor
misters.

For
outdoor
automatic
misters,
the
exposure
durations
used
in
the
short­
term
inhalation
exposure
(
5
hours/
day
for
adults,
3
hours/
day
for
toddlers)
represent
the
95th
percentile
values
for
time
spent
outdoors
at
a
restaurant/
picnic
area
(
USEPA,
1997).
During
this
exposure
period
the
individual
is
assumed
to
be
exposed
to
the
average
air
concentration
following
2
spray
events
each
lasting
a
period
of
either
1
minute
or
30
seconds.
Inhalation
risks
of
concern
are
seen
when
exposure
results
from
air
concentrations
after
2,
1­
minute
spray
durations.
Although
this
spray
duration
is
considered
reasonable,
lower
spray
durations
(
i.
e.,
20­
or
30­
second
durations)
may
be
more
representative
of
actual
system
rates.
Standard
label
language
for
use
rates
could
provide
a
more
refined
risk
assessment.
Label
language
requiring
systems
to
activate
at
times
when
people
are
not
present
(
i.
e.,
EPA
Reg.
No.
1021­
1785)
or
systems
with
motion
detectors
would
also
significantly
reduce
inhalation
exposure.
Risks
were
calculated
based
on
automatic
dispersions
(
i.
e.,
2­
6
pre­
set
spray
events
per
day)
throughout
the
day.
It
was
noted
in
the
CSPA
discussion
paper
that
the
systems
can
be
manually
activated
by
the
homeowner.
Although
costs
of
re­
filling
and
service
maintenance
costs
would
likely
deter
homeowners
from
frequent
or
over­
use,
label
language
indicating
appropriate
daily
spray
cycles
should
be
considered.

11.0
DATA
NEEDS
11.1
Product
Chemistry
Data
Requirements
Outstanding
product
chemistry
data
requirements
for
piperonyl
butoxide
Technical
Grade
Active
Ingredients
are
listed
for
each
individual
registrant
in
Table
1
of
the
Product
and
Residue
Chemistry
Document
(
T.
Morton,
D288366,
6/
30/
04).
In
addition,
the
Agency
requires
that
the
registrants
of
all
products
listed
in
Table
1
submit
updated
Confidential
Statements
of
Formulation
for
all
basic
and
alternate
formulations
on
which
the
name
of
the
producer
or
producers
and
the
site(
s)
where
the
piperonyl
butoxide
TGAIs
are
produced
are
clearly
identified.
Page
52
of
61
11.2
Residue
Chemistry
Data
Requirements
C
Label
revisions
and
clarifications
are
required
for
some
crops
in
order
to
reflect
the
use
pattern
parameters
for
which
adequate
residue
data
are
available.

C
Further
analytical
work
to
upgrade
the
previously
submitted
oral
metabolism
studies
with
ruminant
and
poultry.
Representative
egg,
milk,
and
tissue
samples
from
the
dermal
or
oral
ruminant/
poultry
metabolism
studies
must
be
analyzed
using
the
enforcement
method
or
any
preferred
data­
collection
method
to
determine
whether
the
method(
s)
adequately
recover
Piperonyl
butoxide
residues
of
concern.
Data
are
under
review.

C
Additional
storage
stability
data
for
plant
(
and
processed)
and
livestock
commodities
to
upgrade
previously
submitted
studies
or
to
support
new
studies.

C
Data
to
support
uses
of
piperonyl
butoxide
on
foods
stored
in
multi­
walled
paper
or
cloth
bags.

C
A
magnitude
of
the
residue
study
with
ruminants
reflecting
premise
treatment.
In
addition,
the
registrants
need
to
perform
further
analysis
on
milk
samples
from
the
dermal
and
oral
studies.

C
A
magnitude
of
the
residue
study
with
poultry
reflecting
direct
applications
to
laying
hens
using
a
10%
dust
formulation.

C
Magnitude
of
the
residue
studies
reflecting
preharvest
uses
on
representative
commodities
of
all
crop
groups
(
and
a
few
miscellaneous
commodities)
which
are
being
supported
for
reregistration.

C
Magnitude
of
the
residue
studies
reflecting
postharvest
uses
for
all
crops
(
except
potato
and
sweet
potato)
which
are
being
supported
for
reregistration
C
Processing
studies
on
apple,
barley,
coconut,
corn
(
field),
fig,
flax,
oat,
peanut,
pineapple,
plum,
potato,
rice,
rye,
sorghum,
and
wheat.

C
A
confined
rotational
crop
study.
A
field
accumulation
study
in
rotational
crops
(
OPPTS
860.1900)
is
required
if
the
level
of
the
total
radioactive
residue
in
the
confined
rotational
crops
is
equal
to
or
exceeds
0.01
ppm
at
the
desired
rotational
interval
or
at
12
months,
and
once
the
nature
of
the
residue
in
the
rotational
crops
is
understood.
Page
53
of
61
Tables
13­
21
­
Residential
Exposure
and
Risk
Estimates
Table
13.
Piperonyl
Butoxide
Inhalation
Exposure
&
MOEs
for
Residential
Handler
Activities
Target
Short
and
Intermediate
Term
MOE
=
300
Exposure
Scenario
Inhalation
Unit
Exposure
(
µ
g/
lb
ai)
1
Crop2
Application
Rate3
Daily
Area
Treated4
Inhalation
Dose
(
mg/
kg/
day)
5
Inhalation
MOE6
Mixing/
Loading/
Applying
Liquids
for
Low
Pressure
Handwand
application
(
1)
30
Indoor
Residential
Surface
Spray
0.56
lb
ai
per
1000
ft2
1
home
of
avg
area
of
1600
sf
0.0004
10400
Mixing/
Loading/
Applying
Liquids
for
Low
Pressure
Handwand
application
(
2)
30
Indoor
Residential
Crack
&
Crevice
2.2
lb
ai
per
1000
ft2
1
home
of
avg
area
of
1600
sf
0.0015
2700
Mixing/
Loading/
Applying
Liquids
for
Garden
hose­
end
sprayer
application
(
3)
11
Lawn
1
lb
ai
per
acre
0.5
Acres
per
day
0.000079
51000
1Baseline
inhalation
unit
exposures
represent
no
respirator.
Values
are
reported
in
the
PHED
Surrogate
Exposure
Guide
dated
August
1998
or
are
from
data
submitted
by
the
Outdoor
Residential
Exposure
Task
Force
dated
May
2000.
2Crops
and
use
patterns
are
from
the
master
label
3Application
rates
are
based
on
maximum
values
provided
in
the
master
label
Most
application
rates
upon
which
the
analysis
is
based
are
presented
as
lb
ai/
A.
In
some
cases,
the
application
rate
is
based
on
applying
a
solution
at
concentrations
specified
by
the
label
(
i.
e.,
presented
as
lb
ai/
gallon).
4Amount
treated
is
based
on
the
area
or
gallons
that
can
be
reasonably
applied
in
a
single
day
for
each
exposure
scenario
of
concern
based
on
the
application
method
and
formulation/
packaging
type.
(
Standard
EPA/
OPP/
HED
values).
5Inhalation
dose
(
mg/
kg/
day)
=
[
unit
exposure
(
ug/
lb
ai)
*
0.001
mg/
g
unit
conversion
*
Inhalation
absorption
(
100%)
*
Application
rate
(
lb
ai/
acre
or
lb
ai/
gallon)
*
Daily
area
treated
(
acres
or
gallons)]
/
Body
weight
(
70
kg).
6Inhalation
MOE
=
short­
term
and
intermediate­
term
endpoint
for
inhalation;
4
mg/
kg/
day
(
inhalation
LOAEL)/
Daily
Inhalation
Dose.
Target
Short
and
Intermediate
Term
Inhalation
MOE
is
300.
Target
Long
Term
Inhalation
MOE
is
1000.

Table
14.
Piperonyl
Butoxide
Inhalation
Exposure
&
MOEs
for
Residential
Handler
Activities
for
Outdoor
Automatic
Mister
(
4)
Application
Rate
(
lb
PBO/
gal)
Reservoir
size
(
gallons)
System
Maintenance
(
tanks
filled/
day)
Daily
Dose
(
mg/
kg/
day)
Acute
(
Target
MOE
=
100)
ST/
IT
(
Target
MOE
=
300)

0.0384
55
1
0.0000362
17000000
110000
250
1
0.0001645
3800000
24000
1
Daily
Dose
(
mg/
kg/
day)
=
[
Application
Rate
(
lb
PBO/
gal
soln)
*
Unit
Exposure
(
1.2
ug/
lb
PBO
handled)
*
Holding
Tank
Size
(
gallons/
tank)
*
System
Maint.
(
tanks/
day)
*
Inhalation
Abs.
Factor
(
100%)]
/
[
CF
(
1000
ug/
mg)
*
Body
Weight
(
70
kg)]
2
MOE
=
Acute
NOAEL
(
630
mg/
kg/
day)
/
Daily
Dose
(
mg/
kg/
day)
or
ST/
IT
LOAEL
(
3.91
mg/
kg/
day)
/
Daily
Dose
(
mg/
kg/
day)

Table
15.
Piperonyl
Butoxide
Post­
application
Inhalation
Risks
To
Adults
and
Children
Following
Mosquito
Adulticide
Application
­
Acute
Target
MOE
=
100
Exposed
Individual
Breathing
Zone
Concentration
(
mg/
m3)
Breathing
Rate
(
m3/
hr)
Inhalation
Dose
(
mg/
kg/
day)
1
MOE
Aerial
Spray
(
Fixed
Wing
and
Rotary
Aircraft)
(
1)

Adult
0.03
1.0
0.0009
740000
Child
0.03
0.8
0.004
160000
Truck
Mounted
ULV
Sprayer
(
2)

Adult
0.3
1.0
0.005
75000
Table
15.
Piperonyl
Butoxide
Post­
application
Inhalation
Risks
To
Adults
and
Children
Following
Mosquito
Adulticide
Application
­
Acute
Target
MOE
=
100
Exposed
Individual
Breathing
Zone
Concentration
(
mg/
m3)
Breathing
Rate
(
m3/
hr)
Inhalation
Dose
(
mg/
kg/
day)
1
MOE
Page
54
of
61
Child
0.3
0.8
0014
20000
ID
(
mg/
kg/
day)
=
Inhalation
Dose
=
PDR/
BW
PDR
(
t)
(
mg/
day)
=
((
AR
t)
(
lb
ai/
A)­
BZC
*
BR
*
ED
where:
PDR
=
Potential
Dose
Rate
­
inhalation
dose
in
breathing
zone
after
spray
application
(
mg/
m3)
AR
=
application
rate
lb/
ai
per
acre
converted
to
mg/
m3
BZC
=
Breathing
Zone
Concentration
(
mg/
m3)
­
from
Ag
Drift
Model
for
aerial
spray
application;
1%
of
application
rate
for
truck
mounted
ULV
sprayer
application
BR
=
Breathing
rate
for
adult
or
child
(
m3/
hr)
(
1.0
m3/
hr
adult,
0.8
m3/
hr
child)
BW
=
70
kg
for
adult;
15
kg
for
toddler
ED
=
Exposure
Duration
(
2
hr/
day)
MOE
=
Acute
Inhalation
NOAEL
(
630
mg/
kg/
day)/
Inhalation
Dose
(
mg/
kg/
day)
MOEs
are
reported
to
two
significant
figures.

Table
16.
Piperonyl
Butoxide
Post­
application
Incidental
Ingestion
Risks
to
Toddlers
Reentering
Treated
Lawns
Hand
to
Mouth
(
HTM),
Object
to
Mouth
(
OTM),
Incidental
Soil
Ingestion
(
SI),
Aggregate
­
Short­
Term
Target
MOE
=
100
Inputs
Hand
to
Mouth
(
3)
Object
to
Mouth
(
4)
Soil
Ingestion
(
5)
Aggregate
Max
App
Rate
(
lb
ai/
A)
Hand
Transfer
(
ug/
cm2)
Daily
Oral
Dose
(
mg/
kg/
day)
MOE
Dislogeable
Foliar
Residue
(
ug/
cm2)
Daily
Oral
Dose
(
m/
k/
d)
MOE3
Soil
Residue
(
ug/
g)
Daily
Oral
Dose
(
m/
k/
d)
MOE
Aggregate
MOE
1.0
0.56
0.015
6000
2.2
0.004
24000
0.00075
0.00005
>
1E+
06
4800
1
DOD(
mg/
kg/
day)
=
Daily
Oral
Dose
(
PDR/
BW)
BW
=
15
kg
for
toddler
Hand
To
Mouth
Calculation
PDR
(
t)
(
mg/
day)
=
(
HTF
(
t)
(
µ
g/
cm2)
*
SEF
*
SA
*
Freq
*
ED/
1000
(
µ
g/
mg)
where:
PDR
=
Potential
Dose
Rate
at
time
(
t)
attributable
for
activity
in
a
previously
treated
area
(
mg/
day)
HTE
(
t)
=
Hand
Transfer
Efficiency
at
time
t
=
5%
of
Application
Rate
(
µ
g/
cm2)
SEF
=
Saliva
Extraction
Factor
(
50%)
SA
=
Surface
Area
of
Two
Fingers
(
20
cm2)
Freq
=
Frequency
of
Hand
to
Mouth
Events
(
20)
ED
=
Exposure
Duration
in
hours
(
2
hr/
day)
t
=
Postapplication
Day
on
which
exposure
is
being
assessed
(
day
0)
MOE
=
Short
Term
Oral
NOAEL
(
89
mg/
kg/
day)/
Daily
Oral
Dose
(
mg/
kg/
day)
Object
to
Mouth
Calculation
PDR
(
t)
(
mg/
day)
=
(
DFR
(
t)
(
µ
g/
cm2)
*
SA/
1000
(
µ
g/
mg)
where:
PDR
=
Potential
Dose
Rate
at
time
(
t)
attributable
for
activity
in
a
previously
treated
area
(
mg/
day)
DFR
(
t)=
Dislogeable
Foliar
Residue
at
time
t
=
20%
of
Application
Rate
(
µ
g/
cm2)
SA
=
Surface
Area
of
grass
or
toy
mouthed
by
toddler
(
25
cm2
day)
t
=
Postapplication
day
on
which
exposure
is
being
assessed
(
day
0)
MOE
=
Short
Term
Oral
NOAEL
(
25
mg/
kg/
day)/[
Daily
Oral
Dose
(
mg/
kg/
day)
MOEs
are
reported
to
two
significant
figures
Soil
Ingestion
Calculation
PDR
(
t)
(
mg/
day)
=
(
SR
t
*
IgR
*
CF1)
where:
PDR
=
Potential
Dose
Rate
­
nondietary
ingestion
rate
from
contact
with
treated
surface
(
mg/
day)
SR
t
=
Soil
Residue
on
day
"
t"
(
µ
g/
g)

IgR
=
Ingestion
Rate
of
soil
(
mg/
day);
(
100
mg/
day)
CF1
=
Weight
unit
conversion
factor
(
1E­
6
g/
µ
g)
where:
SR
t
=
Application
Rate
(
µ
g/
cm2)
*
1/
cm
*
0.67
cm3/
g
soil
[
1/
cm
is
fraction
of
ai
available
in
uppermost
cm
of
soil]
t
=
Postapplication
Day
on
which
exposure
is
being
assessed,
assumed
to
be
day
zero
MOE
=
Short
Term
Oral
NOAEL
(
25
mg/
kg/
day)/[
Daily
Oral
Dose
(
mg/
kg/
day)
MOEs
are
reported
to
two
significant
figures
AggMOE=
1/(
1/
MOE
HTM
+
1/
MOE
OTM
+
1/
MOE
SI)
Page
55
of
61
Table
17.
Piperonyl
Butoxide
Post­
application
Incidental
Ingestion
Risks
To
Toddlers
Playing
on
Vinyl
Floor
and
Carpet
after
Treatment
with
Fogger
Formulation
­
Short­
Term
Target
MOE
=
100
Indoor
Surface
Indoor
Surface
Residue
(
ug/
cm2)
Hand
Transfer
Efficiency
(%)
Daily
Oral
Dose
(
mg/
kg/
day)
1
MOE
carpet
(
6)
10
13
0.021
4200
vinyl
(
7)
10
8
0.035
2600
1
DOD(
mg/
kg/
day)
=
Daily
Oral
Dose
=
PDR/
BW
PDR
(
t)
(
mg/
day)
=
(
ISR
t)
(
µ
g/
cm2)
*
TE
*
SEF
*
SA
*
Freq
*
ED/
1000
(
µ
g/
mg)
where:
PDR
=
Potential
Dose
Rate
on
day
of
application
(
mg/
day)
ISR
=
Indoor
Surface
Residue
(
µ
g/
cm2)
at
maximum
AR
of
0.033
lbs
ai/
1000
ft2
HTE
=
Hand
Transfer
Efficiency
­
transfer
of
(
13%
for
carpet;
8%
for
vinyl)
SEF
=
Saliva
Extraction
Factor
(
50%)
SA
=
Surface
Area
of
Two
Fingers
(
20
cm2)
Freq
=
Frequency
of
Hand
to
Mouth
Events
(
20)
ED
=
Exposure
Duration
in
hours
=
2
hr/
day
t
=
Postapplication
Day
on
which
exposure
is
being
assessed
(
day
0)
BW
=
15
kg
for
toddler
MOE
=
Short
Term
Oral
NOAEL
(
89
mg/
kg/
day)/
Daily
Oral
Dose
(
mg/
kg/
day)
MOEs
are
reported
to
two
significant
figures.

Table
18.
Piperonyl
Butoxide
Post­
application
Incidental
Ingestion
Risks
To
Toddlers
Playing
with
Pets
after
Treatment
with
Spray
Formulation
­
Short­
Term
Target
MOE
=
100
Application
Method
AR
(
mg
ai/
cm2)
Transferable
Residue
(%)
Daily
Oral
Dose
(
mg/
kg/
day)
1
MOE
Aerosol
Spray
(
8)
1.14
20
0.15
600
1
DOD(
mg/
kg/
day)
=
Daily
Oral
Dose
=
PDR/
BW
PDR
(
t)
(
mg/
day)
=
((
AR
t)
(
mg
ai/
animal)
*
F)/
SA
pet
)
*
SEF
*
SA
hands
*
Freq
where:
PDR
=
Potential
Dose
Rate
­
nondietary
ingestion
dose
from
contact
with
treated
pets
(
mg/
day)
AR
=
Application
Rate
or
amount
applied
to
animal
in
a
single
treatment
(
mg
ai/
animal)
=
½
of
16
oz
spray
container
with
maximum
of
3%
ai
per
6000
cm2/
animal
F
AR
=
Fraction
of
Application
Rate
available
for
dermal
contact
as
transferable
residue
(
20%)
SA
pet
=
Surface
Area
of
a
treated
dog
(
6000
cm2/
animal)
t
=
Time
After
Application
(
0
days)
SEF
=
Saliva
Extraction
Factor
(
50%)
SA
hands
=
Surface
Area
of
the
hands
(
20
cm2)
Freq
=
Hand­
to­
Mouth
Events
(
1
event/
day)
BW
=
15
kg
for
toddler
MOE
=
Short
Term
Oral
NOAEL
(
89
mg/
kg/
day)/
Daily
Oral
Dose
(
mg/
kg/
day)
MOEs
are
reported
to
two
significant
figures.

Table
19.
Piperonyl
Butoxide
Inhalation
Risks
To
Adults
and
Children
During
and
After
Indoor
Space
Spray
Application
­
Acute
Target
MOE
=
100
Application
Method
Exposed
Individual
Breathing
Zone
Concentration
(
mg/
m3)
Breathing
Rate
(
m3/
hr)
Inhalation
Dose
(
mg/
kg/
day)
1
MOE
Aerosol
Spray
(
9)
Adult
5.8
1.0
0.09
3800
Child
5.8
0.8
0.28
1000
Inhalation
Dose
(
mg/
kg/
day)
=
PDR/
BW
PDR
(
t)
(
mg/
day)
=
((
AR
t)
(
lb
ai/
A)­
BZC
*
BR
*
ED
where:
PDR
=
Potential
Dose
Rate
­
inhalation
dose
in
breathing
zone
after
spray
application
(
mg/
m3)
AR
=
application
rate
­
1
16
oz
can
containing
2.5%
ai
applied
to
a
16
x
16
x
8
ft
room
BZC
=
Breathing
Zone
Concentration
(
mg/
m3)
­
measured
air
concentration
from
NDETF
study
adjusted
to
reflect
a
likely
maximum
application
rate
BR
=
Breathing
rate
for
adult
or
child
(
m3/
hr)
(
1.0
m3/
hr
adult,
0.8
m3/
hr
child)
BW
=
70
kg
for
adult;
15
kg
for
toddler
ED
=
Exposure
Duration
(
2
hr/
day)
34
Page
56
of
61
MOE
=
Acute
Inhalation
NOAEL
(
630
mg/
kg/
day)/
Inhalation
Dose
(
mg/
kg/
day)
MOEs
are
reported
to
two
significant
figures.

Table
20.
Outdoor
Automatic
Mister
Residential
Outdoor
Bystander
 
Acute
Inhalation
Exposure
and
Risk
Estimates
(
10)

Population
Sub­
Group
Application
Rate
(
lb
PBO/
ft3­
min)
Air
Concentration1
(
mg
PBO/
m3)
Inhalation
Rate
(
m3/
hour)
Daily
Dose2
(
mg/
kg/
day)
MOE3
(
Target
MOE
=
100)

Adult
0.000000469
7.50974
1
0.00179
350000
Toddler
0.000000469
7.50974
0.7
0.00585
110000
1
Air
Concentration
(
mg
PBO/
m3)
=
Application
Rate
(
lb
PBO/
ft3­
min)
*
CF
(
454000
mg/
lb)
*
CF
(
35
ft3/
m3)
*
#
Spray
Events
(
1)
*
Spray
Duration
(
1
minute)
2
Daily
Dose
(
mg/
kg/
day)
=
[
Air
Concentration
(
mg
PBO/
m3)
*
Inhalation
Rate
(
m3/
hr)
*
Inhalation
Abs.
Factor
(
100%)
*
Exposure
Duration
(
0.0167
hrs/
day)]
/
Body
Weight
(
kg)
3
MOE
=
Acute
NOAEL
(
630
mg/
kg/
day)
/
Daily
Dose
(
mg/
kg/
day)

Table
21.
Outdoor
Automatic
Mister
Residential
Outdoor
Bystander
 
Short­
Term
Inhalation
Exposure
and
Risk
Estimates
(
11)

Population
Sub­
Group
Application
Rate
(
lb
PBO/
ft3­
min)
Inhalation
Rate
(
m3/
hour)
Spray
Duration
(
minutes)
Air
Concentration1
(
mg
PBO/
m3)
Daily
Dose2
(
mg/
kg/
day)
MOE3
(
Target
MOE
=
300)

Adult
0.000000469
1
1
0.150195
0.010728
360
0.5
0.0750974
0.005364
730
Toddler
0.000000469
0.7
1
0.150195
0.0210273
190
0.5
0.0750974
0.0105136
370
1
Air
Concentration
(
mg
PBO/
m3)
=
[
Application
Rate
(
lb
PBO/
ft3­
min)
*
CF
(
454000
mg/
lb)
*
CF
(
35
ft3/
m3)
*
#
Spray
Events
(
2)
*
Spray
Duration
(
min)]/
Dilution
Factor
(
100)
2
Daily
Dose
(
mg/
kg/
day)
=
[
Air
Concentration
(
mg
PBO/
m3)
*
Exposure
Duration
(
hrs/
day)
*
Inhalation
Rate
(
m3/
hr)
*
Inhalation
Abs.
Factor
(
100%)]/
Body
Weight
(
kg)
3
MOE
=
ST/
IT
NOAEL
(
3.91
mg/
kg/
day)
/
Daily
Dose
(
mg/
kg/
day)

Tables
19­
23
 
Occupational
Exposure
and
Risk
Estimates
Table
22.
Piperonyl
Butoxide
Inhalation
Exposure
&
MOEs
for
Agricultural
Handler
Activities
Target
Short
and
Intermediate
Term
MOE
=
300
Exposure
Scenario
Inhalation
Unit
Exposure
(
µ
g/
lb
ai)
1
Crop2
Application
Rate3
Daily
Area
Treated4
Inhalation
Dose
(
mg/
kg/
day)
5
Inhalatio
n
MOE6
Mixer/
Loader
Mixing/
Loading
Liquids
for
Aerial
and/
or
Chemigation
application
(
1)
1.2
Field
Crops
0.50
lb
ai/
acre
350
Acres/
day
0.003
1300
High
Acre
Crops
1200
A/
day
0.01
380
Mixing/
Loading
Liquids
for
Groundboom
application
(
2)
1.2
Field
Crops
0.5
lb
ai/
acre
80
Acres/
day
0.00069
5800
Mixing/
Loading
Liquids
for
Airblast
application
(
3)
1.2
Field
Crops
0.5
lb
ai
per
acre
40
Acres/
day
0.00021
19000
Mixing/
Loading
Wettable
Powders
for
Aerial
application
and/
or
Chemigation
application
(
4)
43
Field
Crops
0.50
lb
ai/
acre
350
Acres/
day
0.11
40
0.06
lb
ai/
acre
0.013
310
High
Acre
Crops
0.50
lb
ai/
acre
1200
Acres/
day
0.37
11
0.018
lb
ai/
acre
0.013
300
Table
22.
Piperonyl
Butoxide
Inhalation
Exposure
&
MOEs
for
Agricultural
Handler
Activities
Target
Short
and
Intermediate
Term
MOE
=
300
Exposure
Scenario
Inhalation
Unit
Exposure
(
µ
g/
lb
ai)
1
Crop2
Application
Rate3
Daily
Area
Treated4
Inhalation
Dose
(
mg/
kg/
day)
5
Inhalatio
n
MOE6
Page
57
of
61
Mixing/
Loading
Wettable
Powders
for
Groundboom
application
(
5)
43
Field
Crops
0.50
lb
ai/
acre
80
Acres/
day
0.025
160
0.25
lb
ai/
acre
0.012
325
Mixing/
Loading
Wettable
Powders
for
Airblast
application
(
6)
43
Field
Crops
0.50
lb
ai/
acre
40
Acres/
day
0.012
330
Applicator
Sprays
for
Aerial
application
(
7)
0.07
Field
Crops
0.50
lb
ai/
acre
350
Acres/
day
0.00018
23000
Sprays
for
Groundboom
applic
(
8)
0.74
Field
Crops
0.50
lb
ai/
acre
80
Acres/
day
0.00042
9500
Sprays
for
Airblast
application
(
9)
4.5
Field
Crops
0.50
lb
ai/
acre
40
Acres/
day
0.0013
3100
Mixer/
Loader/
Applicator
Mixing/
Loading/
Applying
Liquids
for
High­
Pressure
Handwand
application
(
10)
120
Greenhouse
1.5
lb
ai/
acre
10
Acres/
day
0.026
160
0.07
lb
ai/
acre
0.012
330
Mixing/
Loading/
Applying
Liquids
for
Low
Pressure
Handwand
or
Backpack
Sprayer
application
(
11)
30
Greenhouse
1.5
lb
ai/
acre
2
Acres/
day
0.0013
3100
Mixing/
Loading/
Applying
Wettable
Powders
for
Low­
Pressure
Handwand
or
Backpack
Sprayer
application
(
12)
1100
Greenhouse
1.5
lb
ai/
acre
2
Acres/
day
0.05
85
0.4
lb
ai/
acre
0.013
320
Mixing/
Loading/
Applying
Liquids
for
Low
Pressure
Handwand
or
Backpack
Sprayer
application
(
13)
30
Outdoor
Premise
&
Equipment
1
lb
lb
ai/
acre
2
Acres/
day
0.0009
4700
Flagger
Flagging
for
Spray
application
(
14)
0.35
Field
Crops
0.5
lb
ai
per
acre
350
Acres
per
day
0.00088
4600
1Baseline
inhalation
unit
exposures
represent
no
respirator.
Values
are
reported
in
the
PHED
Surrogate
Exposure
Guide
dated
August
1998
or
are
from
data
submitted
by
the
Outdoor
Residential
Exposure
Task
Force
dated
May
2000.
2Crops
and
use
patterns
are
from
the
master
label
3Application
rates
are
based
on
maximum
values
provided
in
the
master
label
Most
application
rates
upon
which
the
analysis
is
based
are
presented
as
lb
ai/
A.
In
some
cases,
the
application
rate
is
based
on
applying
a
solution
at
concentrations
specified
by
the
label
(
i.
e.,
presented
as
lb
ai/
gallon).
4Amount
treated
is
based
on
the
area
or
gallons
that
can
be
reasonably
applied
in
a
single
day
for
each
exposure
scenario
of
concern
based
on
the
application
method
and
formulation/
packaging
type.
(
Standard
EPA/
OPP/
HED
values).
5Inhalation
dose
(
mg/
kg/
day)
=
[
unit
exposure
(
ug/
lb
ai)
*
0.001
mg/
g
unit
conversion
*
Inhalation
absorption
(
100%)
*
Application
rate
(
lb
ai/
acre
or
lb
ai/
gallon)
*
Daily
area
treated
(
acres
or
gallons)]
/
Body
weight
(
70
kg).
6Inhalation
MOE
=
short­
term
and
intermediate­
term
endpoint
for
inhalation;
4
mg/
kg/
day
(
inhalation
LOAEL)/
Daily
Inhalation
Dose.
Target
Short
and
Intermediate
Term
Inhalation
MOE
is
300.
Target
Long
Term
Inhalation
MOE
is
1000.

Table
23
Piperonyl
Butoxide
Inhalation
Exposure
&
MOEs
for
Residential
Handler
Activities
for
Outdoor
Automatic
Mister
(
4)

Application
Rate
(
lb
PBO/
gal)
Reservoir
size
(
gallons)
System
Maintenance
(
tanks
filled/
day)
Daily
Dose1
(
mg/
kg/
day)
Acute
(
Target
MOE
=
100)
ST/
IT
(
Target
MOE
=
300)
Page
58
of
61
0.0384
55
5
0.0002534
3500000
22000
250
5
0.0011516
770000
4800
1
Daily
Dose
(
mg/
kg/
day)
=
[
Application
Rate
(
lb
PBO/
gal
soln)
*
Unit
Exposure
(
1.2
ug/
lb
PBO
handled)
*
Holding
Tank
Size
(
gallons/
tank)
*
System
Maint.
(
tanks/
day)
*
Inhalation
Abs.
Factor
(
100%)]
/
[
CF
(
1000
ug/
mg)
*
Body
Weight
(
70
kg)]
2
MOE
=
Acute
NOAEL
(
630
mg/
kg/
day)
/
Daily
Dose
(
mg/
kg/
day)
or
ST/
IT
LOAEL
(
3.91
mg/
kg/
day)
/
Daily
Dose
(
mg/
kg/
day)

Table
24.
Piperonyl
Butoxide
Inhalation
Exposure
&
MOEs
for
Pesticide
Control
Operator
Activities
Target
Short
and
Intermediate
Term
MOE
=
300
Target
Long
Term
MOE
=
1000
Exposure
Scenario
Inhalation
Unit
Exposure
(
µ
g/
lb
ai)
1
Use2
Application
Rate3
Daily
Area
Treated4
Inhalation
Dose
(
mg/
kg/
day)
5
Inhalation
MOE6
Mixer/
Loader/
Applicator
Mixing/
Loading/
Applying
Liquids
for
Low
Pressure
Handwand
application
­
Surface
Spray
(
1)
30
Indoor
Surface
Spray
0.56
lb
ai
per
1000
sf
7
buildings
avg
area
treated
­
1600
sf
0.0034
1500
Mixing/
Loading/
Applying
Liquids
for
Low
Pressure
Handwand
application
­
Crack
&
Crevice
Treatment
(
2)
30
Indoor
Crack
&
Crevice
2.2
lb
ai
per
1000
sf
7
buildings
avg
area
treated
­
1600
sf
0.12
380
1
building
avg
area
treated
­
1600
sf
0.0004
2700
Mixing/
Loading/
Applying
Wet
Powders
for
Low
Pressure
Handwand
application
­
Surface
Spray
(
3)
1100
Indoor
Surface
Spray
0.56
lb
ai
per
1000
sf
7
buildings
avg
area
treated
­
1600
sf
0.113
40
1
building
avg
area
treated
­
1600
sf
0.0015
280
0.16
lb
ai
per
1000
sf
1
building
avg
area
treated
­
1600
sf
0.004
1020
Mixing/
Loading/
Applying
Wettable
Powders
for
Low
Pressure
Handwand
application
­
Crack
&
Crevice
Treatment
(
4)
1100
Indoor
Crack
&
Crevice
2.2
lb
ai
per
1000
ft2
7
buildings
avg
area
treated
­
1600
sf
0.385
10
1
building
avg
area
treated
­
1600
sf
0.055
70
0.16
lb
ai
per
1000
ft2
1
building
avg
area
treated
­
1600
sf
0.004
1020
Mixing/
Loading/
Applying
Liquids
for
Low
Pressure
Handwand
and
Backpack
Sprayer
application
(
5)
30
Outdoor
Premise
3.5
lb
ai
per
acre
2
acres
per
day
0.003
1300
Mixing/
Loading/
Applying
Liquids
for
Handgun
(
lawn)
Sprayer
application
(
6)
1.8
Lawn
Care
1
lb
ai
per
acre
5
Acres
per
day
0.00013
31000
Mixing/
Loading
Liquids
for
Groundboom
application
(
7)
1.2
Golf
course
1
lb
ai
per
acre
40
Acres
per
day
0.0007
5800
Mixing/
Loading/
Applying
Liquids
for
Low
Pressure
Handwand
and
Backpack
Sprayer
application
(
8)
30
Stored
Grain
0.5
lb
ai
per
1000
ft2
5
bins
per
day
1000
ft2
per
bin
0.0011
3700
Table
24.
Piperonyl
Butoxide
Inhalation
Exposure
&
MOEs
for
Pesticide
Control
Operator
Activities
Target
Short
and
Intermediate
Term
MOE
=
300
Target
Long
Term
MOE
=
1000
Exposure
Scenario
Inhalation
Unit
Exposure
(
µ
g/
lb
ai)
1
Use2
Application
Rate3
Daily
Area
Treated4
Inhalation
Dose
(
mg/
kg/
day)
5
Inhalation
MOE6
Page
59
of
61
Mixing/
Loading/
Applying
Liquids
for
High­
Pressure
Handwand
application
(
9)
120
Stored
Grain
0.5
lb
ai
per
1000
ft2
5
bins
per
day
1000
ft2
per
bin
0.0043
930
Mixing/
Loading/
Applying
Liquids
for
Low­
Pressure
Handwand
application
(
10)
30
Stored
Produce
0.1
lb
ai
per
1000
ft2
5
storage
facilities
per
day
10000
ft2
per
facility
0.0021
1900
Applicator
Sprays
for
Groundboom
application
(
11)
0.74
Golf
course
1
lb
ai
per
acre
40
Acres
per
day
0.0004
9500
Sprays
for
Aerosol
Application
(
12)
1300
Indoor
Space
Spray
0.025
lb
ai
per
16
oz
can
7
homes
per
day
2
cans
per
home
0.0065
615
0.012
lb
ai
per
16
oz
can
0.0033
1200
1Baseline
inhalation
unit
exposures
represent
no
respirator.
Values
are
reported
in
the
PHED
Surrogate
Exposure
Guide
dated
August
1998
or
are
from
data
submitted
by
the
Outdoor
Residential
Exposure
Task
Force
dated
May
2000.
2
Use
patterns
are
from
the
master
label
3Application
rates
are
based
on
maximum
values
provided
in
the
master
label
Most
application
rates
upon
which
the
analysis
is
based
are
presented
as
lb
ai/
A.
In
some
cases,
the
application
rate
is
based
on
applying
a
solution
at
concentrations
specified
by
the
label
(
i.
e.,
presented
as
lb
ai/
gallon).
4Amount
treated
is
based
on
the
area
or
gallons
that
can
be
reasonably
applied
in
a
single
day
for
each
exposure
scenario
of
concern
based
on
the
application
method
and
formulation/
packaging
type.
(
Standard
EPA/
OPP/
HED
values).
5Inhalation
dose
(
mg/
kg/
day)
=
[
unit
exposure
(
ug/
lb
ai)
*
0.001
mg/
g
unit
conversion
*
Inhalation
absorption
(
100%)
*
Application
rate
(
lb
ai/
acre
or
lb
ai/
gallon)
*
Daily
area
treated
(
acres
or
gallons)]
/
Body
weight
(
70
kg).
6Inhalation
MOE
=
short­
term
and
intermediate­
term
endpoint
for
inhalation;
4
mg/
kg/
day
(
inhalation
LOAEL)/
Daily
Inhalation
Dose.
Target
Short
and
Intermediate
Term
Inhalation
MOE
is
300.
Target
Long
Term
Inhalation
MOE
is
1000.

Table
25.
Piperonyl
Butoxide
Inhalation
Exposure
&
MOEs
for
Mosquito
Abatement
Activities
Target
Short
and
Intermediate
Term
MOE
=
300
Target
Long
Term
MOE
=
1000
Exposure
Scenario
Inhalation
Unit
Exposure
(
µ
g/
lb
ai)
1
Use2
Application
Rate3
Daily
Area
Treated4
Inhalation
Dose
(
mg/
kg/
day)
5
Inhalation
MOE6
Mixer/
Loader
Mixing/
Loading
Liquids
for
Aerial
application
(
1)
1.2
Mosquito
Control
0.08
lb
ai
per
acre
7500
Acres
per
day
0.0100
390
0.03
lb
ai
per
acre
0.0040
1000
Mixing/
Loading
Liquids
for
ULV
truck
mounted
spray
application
(
2)
1.2
Mosquito
Control
0.08
lb
ai
per
acre
3000
Acres
per
day
0.0041
970
Mixer/
Loader/
Applicator
Sprays
for
ULV
truck
mounted
spray
(
Airblast
Surrogate
Unit
Exposure)
(
3)
4.5
(
Open
Cab)
Mosquito
control
0.08
lb
ai
per
acre
3000
Acres
per
day
0.0150
260
0.45
(
Closed
Cab)
0.0004
2600
Table
25.
Piperonyl
Butoxide
Inhalation
Exposure
&
MOEs
for
Mosquito
Abatement
Activities
Target
Short
and
Intermediate
Term
MOE
=
300
Target
Long
Term
MOE
=
1000
Exposure
Scenario
Inhalation
Unit
Exposure
(
µ
g/
lb
ai)
1
Use2
Application
Rate3
Daily
Area
Treated4
Inhalation
Dose
(
mg/
kg/
day)
5
Inhalation
MOE6
Page
60
of
61
Mixing/
Loading/
Applying
Liquids
for
Backpack
sprayer
application
(
4)
30
Mosquito
Control
0.08
lb
ai
per
acre
2
acres
per
day
0.00007
58000
1Baseline
inhalation
unit
exposures
represent
no
respirator.
Values
are
reported
in
the
PHED
Surrogate
Exposure
Guide
dated
August
1998
or
are
from
data
submitted
by
the
Outdoor
Residential
Exposure
Task
Force
dated
May
2000.
2Use
patterns
are
from
the
master
label
3Application
rates
are
based
on
maximum
values
provided
in
the
master
label.
Most
application
rates
upon
which
the
analysis
is
based
are
presented
as
lb
ai/
A.
In
some
cases,
the
application
rate
is
based
on
applying
a
solution
at
concentrations
specified
by
the
label
(
i.
e.,
presented
as
lb
ai/
gallon).
4Amount
treated
is
based
on
the
area
or
gallons
that
can
be
reasonably
applied
in
a
single
day
for
each
exposure
scenario
of
concern
based
on
the
application
method
and
formulation/
packaging
type.
(
Standard
EPA/
OPP/
HED
values).
5Inhalation
dose
(
mg/
kg/
day)
=
[
unit
exposure
(
ug/
lb
ai)
*
0.001
mg/
g
unit
conversion
*
Inhalation
absorption
(
100%)
*
Application
rate
(
lb
ai/
acre
or
lb
ai/
gallon)
*
Daily
area
treated
(
acres
or
gallons)]
/
Body
weight
(
70
kg).
6Inhalation
MOE
=
short­
term
and
intermediate­
term
endpoint
for
inhalation;
4
mg/
kg/
day
(
inhalation
LOAEL)/
Daily
Inhalation
Dose.
Target
Short
and
Intermediate
Term
Inhalation
MOE
is
300.
Target
Long
Term
Inhalation
MOE
is
1000.

Table
26.
Piperonyl
Butoxide
Inhalation
Exposure
&
MOEs
for
Pet
Groomer
and
Veterinarian
Activities
Target
Short
and
Intermediate
Term
MOE
=
300
Long­
Term
MOE
=
1000
Exposure
Scenario
Inhalation
Unit
Exposure
(
µ
g/
lb
ai)
1
Use2
Application
Rate3
Daily
Area
Treated4
Inhalation
Dose
(
mg/
kg/
day)
5
Inhalation
MOE6
Aerosol
Application
1300
Pet
Spray
0.03
lb
ai
per
16
oz
can
8
pets
treated
per
day
½
can
of
spray
per
pet
0.002
1800
1Baseline
inhalation
unit
exposures
represent
no
respirator.
Values
are
reported
in
the
PHED
Surrogate
Exposure
Guide
dated
August
1998
or
are
from
data
submitted
by
the
Outdoor
Residential
Exposure
Task
Force
dated
May
2000.
2
Use
pattern
is
from
the
master
label
3Application
rates
are
based
on
maximum
values
provided
in
the
master
label
4Amount
treated
is
based
on
the
area
or
gallons
that
can
be
reasonably
applied
in
a
single
day
for
each
exposure
scenario
of
concern
based
on
the
application
method
and
formulation/
packaging
type.
(
Standard
EPA/
OPP/
HED
values).
5Inhalation
dose
(
mg/
kg/
day)
=
[
unit
exposure
(
ug/
lb
ai)
*
0.001
mg/
g
unit
conversion
*
Inhalation
absorption
(
100%)
*
Application
rate
(
lb
ai/
acre
or
lb
ai/
gallon)
*
Daily
area
treated
(
acres
or
gallons)]
/
Body
weight
(
70
kg).
6Inhalation
MOE
=
short­
term
and
intermediate­
term
endpoint
for
inhalation;
4
mg/
kg/
day
(
inhalation
LOAEL)/
Daily
Inhalation
Dose.
Target
Short
and
Intermediate
Term
Inhalation
MOE
is
300.
Target
Long
Term
Inhalation
MOE
is
1000.
Page
61
of
61
O
O
O
O
O
O
PBO
prop­
1­
one
"
M16"

O
O
O
O
PBO
prop­
1­
one
benzaldehyde
"
M11"

O
O
OH
O
O
O
O
OH
5[
2­(
2­
butoxyethoxy)­
hydroxymethyl]­
6­
carboxy­
1,3­
benzodioxole
"
M8"

O
O
O
O
O
PBO­
alcohol
dimer
PBO
PBO
Degradation:
Aerobic
Soil
Pathway
2
PBO­
acid
PBO­
alcohol
(
Soil
Photodeg.
only)
Attachment
1
