EPA
Registration
Division
contact:
Barbara
Madden,
(
703)
305­
6463
Petition
Numbers
5E6965,
5E6966,
and
5E6967
Summary
of
Petitions
EPA
has
received
pesticide
petitions
(
PP#
5E6965,
5E6966,
and
5E6967)
from
Interregional
Research
Project
#
4
(
IR­
4),
681
US
Highway
#
1
South,
North
Brunswick,
NJ
08902­
3390,
proposing,
pursuant
to
section
408(
d)
of
the
Federal
Food,
Drug,
and
Cosmetic
Act
(
FFDCA),
21
U.
S.
C.
346a(
d),
to
amend
40
CFR
part
180.377
by
establishing
tolerances
for
residues
of
diflubenzuron,
(
N­
[[(
4­
chlorophenyl)
amino]
carbonyl]­
2,6­
difluorobenzamide
and
metabolites
convertible
to
pchloroaniline
expressed
as
diflubenzuron]
in
or
on
the
raw
agricultural
commodities
[
brassica,
leafy
greens
subgroup
5B
and
turnip
greens
at
8.0
ppm,
eggplant
and
okra
at
1.0
ppm,
peanut
at
0.2
ppm,
barley
grain,
oat
grain,
wheat
grain
at
0.06
ppm,
forage
of
barley,
oat
and
wheat
at
5.0
ppm,
hay
of
barley,
oat
and
wheat
at
2.0
ppm,
straw
of
barley,
oat
and
wheat
at
2.0
ppm,
and
aspirated
grain
fractions
of
barley,
oat
and
wheat
at
3.0
ppm
and
pummelo
at
0.5
ppm.]
EPA
has
determined
that
the
petition
contains
data
or
information
regarding
the
elements
set
forth
in
section
408(
d)(
2)
of
the
FFDCA;
however,
EPA
has
not
fully
evaluated
the
sufficiency
of
the
submitted
data
at
this
time
or
whether
the
data
supports
granting
of
the
petition.
Additional
data
may
be
needed
before
EPA
rules
on
the
petition.

A.
Residue
Chemistry
1.
Plant
metabolism.
The
nature
of
the
residue
in
plants
and
livestock
is
adequately
understood.
In
plants,
the
metabolism
of
diflubenzuron
was
investigated
in
soybeans,
oranges
and
rice.
The
main
component
of
residues
in
rice
was
CPU;
levels
of
PCA
were
negligible
to
nondetectable
The
main
component
of
the
residues
in
soybeans
and
oranges
was
the
parent
diflubenzuron
(
DFB).
A
considerable
portion
of
the
residues
were
bound.
DFB
showed
very
limited
absorption
and
translocation
in
plants
with
most
of
the
residues
remaining
on
the
surface.

2.
Analytical
method.
A
practical
analytical
method
for
detecting
and
quantifying
levels
of
diflubenzuron
in
or
on
food
with
a
limit
of
detection
that
allows
monitoring
of
the
residue
at
or
above
the
level
set
in
the
tolerance
was
used
to
determine
residues
in
wheat
and
barley
commodities.

Residues
of
the
individual
analytes
are
detectable
and
quantifiable
using
three
separate
analytical
methods.
Residues
of
diflubenzuron
are
extracted
from
wheat
and
barley
with
dichloromethane
and
are
purified
with
deactivated
florisil.
An
aliquot
of
the
extract
is
hydrolyzed
with
phosphoric
acid
and
the
diflubenzuron
is
partitioned
into
hexane.
The
resulting
extract
is
derivatized
in
heptafluorobutyric
anhydride
(
HFBA).
Quantification
of
diflubenzuron
is
accompanied
by
gas
chromatography
using
electron
capture
detection.

The
analytical
method
for
quantitation
of
the
4­
chlorophenylurea
requires
ethyl
acetate
extraction
of
the
residue
from
the
crop
matrix.
Column
chromatography
is
utilized
for
clean­
up
of
the
extract
immediately
prior
to
derivitiation
with
HFBA.
Derivatized
extracts
are
analyzed
by
gas
chromatography
equipped
with
an
electron
capture
detector.

Analysis
for
the
determination
of
PCA
residues
in
wheat
and
barley
matrices
utilizes
an
internal
standard
method.
Samples
of
matrix
to
be
analyzed
are
fortified
with
an
internal
standard.
Residues
of
14C­
PCA
and
the
internal
standard
are
subjected
to
acid
and
base
hydrolysis.
The
final
extract
is
passed
through
a
florisil
column
for
clean­
up
and
derivatized
with
HFBA
in
hexane.
An
aliquot
of
the
derivatized
extract
is
analyzed
by
gas
chromatography
equipped
with
Mass
Spectrometry
detection.
Recovery
of
PCA
is
determined
from
the
combined
peak
areas
for
the
two
mass
spectral
ions
obtained
from
the
derivatized
PCA
relative
to
the
response
factor
derived
from
the
combined
areas
of
the
corresponding
two
mass
spectral
ions
of
the
internal
standard.

3.
Magnitude
of
residues.
Raw
agricultural
commodities,
treated
according
to
the
proposed
label,
were
sampled.
The
analytical
data
demonstrated
that
residues
in
crops
are
not
expected
to
exceed
the
proposed
tolerance
levels.

Analysis
of
treated
crops
shows
that
the
proposed
tolerances
are
adequate
to
cover
residues
likely
to
be
present
from
the
use
of
diflubenzuron
on
the
proposed
crops.

B.
Toxicological
Profile
1.
Acute
toxicity.
Studies
for
diflubenzuron
technical
indicate
the
acute
oral
toxicity
in
rats
and
mice
is
>
4,640
mg/
kg,
and
the
acute
dermal
toxicity
in
rats
is
>
10,000
mg/
kg.
The
acute
inhalation
LC50
in
rats
is
>
35
mg/
l
(
6
hours).
Diflubenzuron
technical
is
not
an
eye
or
skin
irritant
to
rabbits,
and
is
not
a
dermal
sensitizer
in
guinea
pigs.

2.
Genotoxicity.
Diflubenzuron
did
not
show
any
mutagenic
activity
in
point
mutation
assays
employing
S.
typhimurium,
S.
cerevisiae,
or
L5178Y
Mouse
Lymphoma
cells.
Diflubenzuron
did
not
induce
chromosomal
aberrations
in
Chinese
Hamster
Ovary
cells
and
did
not
induce
unscheduled
DNA
synthesis
in
human
WI­
38
cells.
Diflubenzuron
was
also
negative
in
Mouse
Micronucleus
and
Mouse
Dominant
Lethal
assays
and
it
did
not
induce
cell
transformation
in
Balb/
3T3
cells.

3.
Reproductive
and
developmental
toxicity.
In
a
rat
developmental
toxicity
study,
diflubenzuron
was
administered
by
oral
gavage
to
pregnant
female
rats
at
dosage
levels
of
0,
1,
2
and
4
mg/
kg/
day.
No
treatment
related
effects
were
seen.
A
subsequent
study
was
conducted
in
pregnant
Sprague
Dawley
rats
at
a
dose
of
0
and
1,000
mg/
kg/
day.
No
maternal
toxicity
was
observed.
The
incidence
of
fetuses
with
skeletal
abnormalities
was
slightly
increased
in
the
treated
group,
but
was
within
historical
background
range.
The
NOEL
for
maternal
and
developmental
toxicity
in
rats
was
greater
than
1,000
mg/
kg/
day.
Diflubenzuron
was
also
administered
by
oral
gavage
to
pregnant
New
Zealand
White
rabbits
at
dosage
levels
of
0,
1,
2
and
4
mg/
kg/
day.
No
treatment
related
effects
were
seen.
A
subsequent
study
was
conducted
in
pregnant
rabbits
at
a
dose
of
0
and
1,000
mg/
kg/
day.
No
maternal
or
developmental
toxicity
was
seen.
The
NOEL
for
maternal
and
developmental
toxicity
in
rabbits
was
greater
than
1,000
mg/
kg/
day.

In
a
rat
reproduction
study,
diflubenzuron
was
fed
to
two
generations
of
male
and
female
rats
at
dietary
concentrations
of
0,
10,
20,
40,
and
160
ppm.
No
effects
were
seen
on
parental
body
weight
gain
and
there
were
no
reproductive
effects.
In
a
subsequent
study,
diflubenzuron
was
fed
to
two
generations
of
male
and
female
rats
at
dietary
concentrations
of
500,
5,000
and
50,000
ppm.
Systemic
adult
toxicity
was
seen
at
all
dosage
levels.
No
effects
were
seen
on
reproductive
parameters,
however,
litter
and
mean
pup
weights
of
F1
offspring
were
reduced
at
50,000.
The
NOEL
for
reproductive
toxicity
in
rats
was
50,000
ppm
(
2.5
g/
kg/
day),
and
for
pre­
weaning
development
it
was
5,000
ppm
(
250
mg/
kg/
day).

4.
Subchronic
toxicity.[
To
assess
subchronic
toxicity,
a
four­
week
inhalation
study
and
a
three­
week
dermal
study
were
conducted.
In
the
inhalation
study
rats
were
exposed
nose
only
to
10,
30
or
100
mg/
m3
for
6
hours
per
day,
5
days
per
week
for
4
weeks.
Treatment
related
findings
were
a
slight
reduction
in
erythrocytes,
hemoglobin
and
hematocrit
in
male
and
female
rats
at
a
concentration
of
100
mg/
m3
and
an
increase
in
total
bilirubin
in
high
dose
female
rats.
There
was
no
effect
on
methemoglobin
concentration
at
any
dose
level.
The
NOEL
for
subchronic
inhalation
toxicity
was
30
mg/
m3.

In
the
dermal
toxicity
study,
diflubenzuron
was
applied
to
the
backs
of
male
and
female
CD
rats
for
three
weeks
at
dose
levels
of
20,
500
and
1,000
mg/
kg/
day.
Hematology
evaluation
showed
reductions
in
red
blood
cell
(
RBC),
hemoglobin
(
Hgb)
and
hematocrit
values
at
500
and
1,000
mg/
kg/
day.
An
increased
incidence
of
polychromasia,
hypochromasia
and
anisocytosis
was
seen
at
500
and
1,000
mg/
kg/
day.
An
increase
in
methemoglobin
and
sulfhemoglobin
values
was
seen
at
1,000
mg/
kg/
day.
The
NOEL
for
systemic
toxicity
was
20
mg/
kg/
day.
Also,
a
dermal
absorption
factor
of
0.5%
for
systemic
absorption,
was
derived
from
a
study
where
rats
were
dosed
with
either
0.005
or
0.05
mg/
cm2
of
[
14C]
diflubenzuron
technical.
This
value
can
be
used
for
converting
dermal
exposure
to
oral
equivalents.

5.
Chronic
toxicity.
Diflubenzuron
was
given
by
capsule
to
male
and
female
Beagle
dogs
for
one
year
at
dose
levels
of
0,
2,
10,
50
and
250
mg/
kg/
day.
Body
weight
gain
was
slightly
reduced
in
females
at
250
mg/
kg/
day.
Absolute
liver
and
spleen
weights
were
increased
in
males
given
50
and
250
mg/
kg/
day.
A
reduction
in
hemoglobin
and
mean
corpuscular
hemoglobin
concentration,
with
an
elevation
in
reticulocyte
count,
was
seen
at
50
and
250
mg/
kg/
day.
Methemoglobin
and
sulfhemoglobin
values
were
increased
at
doses
of
10
mg/
kg/
day
and
greater.
Histopathological
findings
were
limited
to
pigmented
macrophages
and
Kupffer
cells
in
the
liver
at
doses
of
50
and
250
mg/
kg/
day.
The
NOEL
for
chronic
toxicity
in
dogs
was
2
mg/
kg/
day.

Diflubenzuron
was
fed
to
male
and
female
Sprague
Dawley
rats
for
two
years
at
dose
levels
of
0,
156,
625,
2,500
and
10,000
ppm.
Methemoglobin
values
were
elevated
in
female
rats
at
all
dose
levels
and
in
male
rats
at
the
two
highest
dose
levels.
Sulfhemoglobin
was
elevated
in
females,
only,
at
dose
levels
of
2,500
and
10,000
ppm.
Mean
corpuscular
volume
(
MCV)
and
reticulocyte
counts
were
increased
in
high
dose
females.
Spleen
and
liver
weights
were
elevated
at
the
two
highest
doses.
Histopathological
examination
demonstrated
an
increase
in
hemosiderosis
of
the
liver
and
spleen,
bone
marrow
and
erythroid
hyperplasia
and
areas
of
cellular
alteration
in
the
liver.
In
another
study
diflubenzuron
was
administered
to
male
and
female
CD
rats
for
two
years
at
dose
levels
of
0,
10,
20,
40
and
160
ppm.
Elevated
methemoglobin
levels
were
seen
in
high
dose
males
and
females.
No
additional
effects,
including
carcinogenic
findings,
were
observed.
The
NOEL
for
chronic
toxicity
in
rats
was
40
ppm
(
2
mg/
kg/
day).

A
ninety­
one
week
oncogenicity
study
in
CFLP
mice
was
conducted
at
doses
of
0,
16,
80,
400,
2,000
and
10,000
ppm.
There
was
no
increase
in
tumor
incidence
as
a
result
of
diflubenzuron
administration.
Target
organ
effects
included:
increased
methemoglobin
and
sulfhemoglobin
values,
Heinz
bodies,
increased
liver
and
spleen
weight,
hepatocyte
enlargement
and
vacuolation,
extramedullary
hemopoiesis
in
the
liver
and
spleen,
siderocytosis
in
the
spleen
and
pigmented
Kupffer
cells.
A
NOEL
for
these
effects
was
16
ppm
(
2
mg/
kg/
day).

Diflubenzuron
was
fed
to
male
and
female
Sprague
Dawley
rats
for
two
years
at
dose
levels
of
0,
156,
625,
2,500
and
10,000
ppm.
Methemoglobin
values
were
elevated
in
female
rats
at
all
dose
levels
and
in
male
rats
at
the
two
highest
dose
levels.
Blood
sulfhemoglobin
was
elevated
in
females,
only,
at
dose
levels
of
2,500
and
10,000
ppm.
MCV
and
reticulocyte
counts
were
increased
in
high
dose
females.
Spleen
and
liver
weights
were
elevated
at
the
two
highest
doses.
Histopathological
examination
demonstrated
an
increase
in
hemosiderosis
of
the
liver
and
spleen,
bone
marrow
and
erythroid
hyperplasia
and
areas
of
cellular
alteration
in
the
liver.
There
was
no
increase
in
tumor
formation.
In
another
study
diflubenzuron
was
administered
to
male
and
female
CD
rats
for
two
years
at
dose
levels
of
0,
10,
20,
40
and
160
ppm.
Elevated
methemoglobin
levels
were
seen
in
high
dose
males
and
females.
No
additional
effects,
including
carcinogenic
findings,
were
observed.

6.
Animal
metabolism.
DFB
in
rats
at
a
single
dose
of
100
mg/
kg
and
5
mg/
kg
single
and
multiple
oral
doses
depicted
limited
absorption
from
the
gastrointestinal
tract.
No
major
difference
was
observed
between
the
single
and
multiple
doses.
In
single
dose
treatments,
after
7
days,
20%
and
3%
of
the
applied
dose
5
and
100
mg/
kg,
respectively
were
excreted
in
urine,
while
79%
and
98%
of
the
applied
dose
5
and
100
mg/
kg,
respectively,
were
eliminated
in
the
feces.
Very
little
bioaccumulation
in
the
tissues
was
observed.
In
the
feces,
only
unchanged
parent
compound
was
detected.
Several
metabolites
were
observed
in
the
urine
which
are,
among
others,
2­
6­
difluorobenzoic
acid
(
DFBA),
2,6­
diflurophippuric
acid,
2­
6­
difluorobenzamide
(
DFBAM),
and
2­
hydroxydiflubenzuron
(
2­
HDFB).
An
unresolved
peak
that
was
characterized
as
p­
chloroaniline
(
PCA)
and/
or
p­
chlorophenylurea
(
CPU)
was
found.
This
latter
peak
accounted
for
about
2%
of
the
administered
dose
(
5
mg/
kg).
To
resolve
if
PCA
and
CPU
are
indeed
metabolites
of
DFB,
rats
were
administered
a
single
oral
dose,
100
mg/
kg
of
14C
DFB.
The
major
metabolites
identified
in
rat
urine
were
4­
chloroaniline­
2­
sulfate,
accounting
for
almost
50%
of
the
total
radioactive
residue
(
TRR)
in
the
urine
and
N­
(
4­
chlorophenyl)
oxamic
acid
which
accounted
for
about
15%
of
the
(
TRR).
Neither
CPU,
PCA
nor
their
N­
hydroxylderivatives
were
found
in
rat
urine
at
a
limit
of
detection
of
23
parts
per
billion
(
ppb).
As
in
the
previous
study,
DFB
was
the
only
residue
found
in
the
feces.

7.
Metabolite
toxicology.
NCI/
NTP
conducted
chronic
feeding
and
gavage
studies
with
pchloroaniline
(
PCA),
a
minor
potential
metabolite
of
diflubenzuron,
in
Fischer
344
rats
and
B6C3F1
mice.

PCA
was
administered
in
the
diet
to
Fischer
344/
N
rats
at
dietary
concentrations
of
250
and
500
ppm
for
78
weeks,
followed
by
a
24
week
observation
period.
A
slight
body
weight
depression
was
seen
in
high
dose
females
rats,
compared
to
controls.
Survival
was
reduced
in
high
dose
males
compared
to
controls.
In
male
rats
there
was
a
slight
increase
in
uncommon
fibromas
or
fibrosarcomas
of
the
spleen,
which
was
not
statistically
significant.
Non­
neoplastic
proliferative
and
chronic
inflammatory
lesions
were
found
in
spleens
of
treated
rats.
It
was
concluded
that,
under
the
conditions
of
the
assay,
sufficient
evidence
was
not
found
to
establish
the
carcinogenicity
of
PCA
for
Fischer
344/
N
rats.

PCA
was
administered
5
days/
week
by
oral
gavage,
as
a
hydrochloride
salt
in
water,
to
male
and
female
F344/
N
rats
at
doses
of
0,
2,
6
or
18
mg/
kg/
day.
Mean
body
weights
of
dosed
rats
were
generally
within
5%
of
those
of
controls
throughout
the
study.
High
dose
animals
generally
showed
mild
hemolytic
anemia
and
dose­
related
methemoglobinemia.
Non­
neoplastic
lesions
seen
were
bone
marrow
hyperplasia,
hepatic
hemosiderosis
and
splenic
fibrosis,
suggesting
treatment
related
effects
on
the
hematopoietic
system.
Adrenal
medullary
hyperplasia
was
observed
in
high
dose
female
rats.
The
incidence
of
uncommon
sarcomas
of
the
spleen
was
significantly
increased
in
high
dose
male
rats.
A
marginal
increase
in
pheochromocytomas
of
the
adrenal
gland
was
seen
in
high
dose
male
and
female
rats.
It
was
concluded
that,
under
the
conditions
of
this
2
year
gavage
study,
there
was
clear
evidence
of
carcinogenic
activity
of
PCA
hydrochloride
for
male
Fischer
344/
N
rats
and
equivocal
evidence
of
carcinogenic
activity
of
PCA
hydrochloride
for
female
Fischer
344/
N
rats.

PCA
was
administered
in
the
diet
to
B6C3F6
mice
at
dietary
concentrations
of
2500
and
5000
ppm
for
78
weeks
followed
by
a
13­
week
observation
period.
A
body
weight
depression
was
seen
in
treated
mice
of
both
sexes,
compared
to
controls.
An
increased
incidence
of
hemangiomas
and
hemangiosarcomas
in
spleen,
kidney,
liver
and
other
sites
was
seen
in
treated
mice
of
both
sexes;
however
this
increase
was
not
statistically
significant
compared
to
controls.
Non­
neoplastic
proliferative
and
chronic
inflammatory
lesions
were
found
in
spleens
of
treated
mice.
The
evidence
was
considered
insufficient
to
conclusively
relate
the
hemangiomatous
tumors
in
mice
to
compound
administration.
It
was
concluded
that,
under
the
conditions
of
the
assay,
sufficient
evidence
was
not
found
to
establish
the
carcinogenicity
of
PCA
for
B6C3F1
mice.
PCA
hydrochloride
was
administered
5
days/
week
by
oral
gavage
to
male
and
female
B6C3F1
mice
at
doses
of
0,
3,
10,
or
30
mg/
kg/
day.
Mean
body
weights
of
high
dose
male
and
female
mice
were
generally
within
5%
of
those
of
controls
throughout
the
study.
The
incidence
of
hepatocellular
adenomas
or
carcinomas
(
combined)
was
increased
in
a
non­
dose­
dependent
manner
in
treated
male
mice.
Metastasis
of
carcinoma
to
the
lung
was
seen
in
the
high
dose
group.
An
increased
incidence
of
hemangiosarcomas
of
the
liver
or
spleen
was
seen
in
high
dose
male
mice.
It
was
concluded
that,
under
the
conditions
of
this
2­
year
gavage
study,
there
was
some
evidence
of
carcinogenic
activity
of
PCA
hydrochloride
for
male
B6C3F1
mice
and
no
evidence
of
carcinogenic
activity
of
PCA
hydrochloride
for
female
B6C3F1
mice.

In
addition
to
PCA,
4­
chlorophenylurea
(
CPU)
is
also
a
potential
minor
metabolite
of
diflubenzuron.
By
association
with
Monuron,
the
EPA
had
assumed
that
CPU
has
oncogenic
potential
with
the
same
carcinogenic
potency
(
q1*)
as
Monuron.
9.
Endocrine
disruption
.
The
standard
battery
of
required
studies
has
been
completed
and
evaluated
to
determine
potential
estrogenic
or
endocrine
effects
of
diflubenzuron.
These
studies
include
an
evaluation
of
the
potential
effects
on
reproduction
and
development,
and
an
evaluation
of
the
pathology
of
the
endocrine
organs
following
repeated
or
long­
term
exposure.
These
studies
are
generally
considered
to
be
sufficient
to
detect
any
endocrine
effects.
No
such
effects
were
noted
in
any
of
the
studies
with
diflubenzuron.

C.
Aggregate
Exposure
1.
Dietary
Exposure.
An
evaluation
of
chronic
dietary
exposure,
including
drinking
water,
has
been
performed
for
the
U.
S.
population
and
various
population
subgroups
including
infants
and
children.
One
day
single
dose
oral
studies
in
rats
and
mice
indicated
there
were
no
significant
acute
effects
observed.
As
only
marginal
effects
were
noted,
an
acute
exposure
assessment
is
not
needed
for
diflubenzuron.

i.
Food.
The
dietary
exposure
from
diflubenzuron
was
estimated
based
on
the
average
residue
values
from
the
various
currently
labeled
raw
agricultural
commodities
(
RAC's),
the
proposed
brassica
leafy
greens
and
turnip
greens,
eggplant
and
okra,
peanut,
barley,
oat
and
wheat
uses.
Percent
of
crop
treated
was
also
factored
into
the
estimate.
Residues
in
meat,
milk
and
egg
products
were
obtained
from
extrapolation
of
metabolism
study
data
to
anticipated
livestock
dietary
burdens.
The
dietary
exposure
analysis
was
estimated
based
on
1989­
92
USDA
food
consumption
data.
For
the
U.
S.
population
(
total),
the
dietary
exposure
of
diflubenzuron
was
estimated
as
0.000172
mg/
kg/
day.
For
nursing
and
non­
nursing
infants,
the
exposure
was
estimated
as
0.000105
and
0.000225
mg/
kg/
day,
respectively.
For
children,
the
exposure
was
0.000303
and
0.000166
mg/
kg/
day
for
1­
6
year
olds
and
7­
12
year
olds,
respectively.

The
dietary
exposure
from
p­
chloroaniline
and
4­
chlorophenylurea
(
CPU)
which
have
been
detected
in
some
food
products
was
also
determined.
Average
residues
or
½
the
LOQ
from
field
trials
for
registered
and
proposed
crops
were
used.
Residues
in
meat,
milk,
and
eggs
were
obtained
from
extrapolation
of
metabolism
data
to
anticipated
livestock
dietary
burdens.
The
percent
treated
of
each
crop
was
also
factored
into
the
exposure
estimate.
For
the
U.
S.
population
(
total),
the
dietary
exposure
of
PCA
was
estimated
at
0.000003
mg/
kg/
day.
For
the
U.
S.
population
(
total),
the
dietary
exposure
of
CPU
was
estimated
at
0.000006
mg/
kg/
day.

ii.
Drinking
water.
[
Diflubenzuron
degrades
in
soil
relatively
quickly
with
an
aerobic
half­
life
ranging
from
3­
7
days.
Major
degradates
include
difluorobenzoic
acid
(
DFBA)
and
CPU.
DFBA
is
further
metabolized
through
decarboxylation
and
ring
cleavage
by
soil
microbes
whereas
CPU
is
slowly
degraded
to
soil­
bound
entities.
Under
anaerobic
aquatic
conditions,
diflubenzuron
has
a
half­
life
of
34
days
with
the
main
degradates
being
DFBA
and
CPU.
In
surface
water,
diflubenzuron
is
degraded
by
microbes
with
a
half­
life
of
5­
10
days.

The
soil
mobility
of
diflubenzuron
is
considered
quite
limited
based
on
a
number
of
experimental
studies
as
well
as
by
computer
modeling.
CPU
has
also
been
shown
to
be
relatively
immobile
in
soil.
Although
DFBA
shows
mobility
in
soil,
it
is
rapidly
degraded.
Therefore,
based
on
results
of
laboratory
and
field
studies,
it
is
not
likely
that
diflubenzuron
or
its
degradates
will
impact
ground
water
quality
to
any
significant
extent.

Based
on
EPA's
SCI­
GRO
and
Tier
II
PRZM­
EXAM
(
IR
and
PC
area)
modeling,
the
average
annual
mean
concentration
of
diflubenzuron
in
ground
and
surface
water
sources
is
not
expected
to
exceed
0.067
ppb
and
0.32
ppb,
respectively.
CPU
in
ground
and
surface
water
is
not
expected
to
exceed
0.065
ppb
and
0.23
ppb,
respectively.
Because
PCA
is
only
a
minor
metabolite
in
the
environment,
it
will
not
be
considered
in
the
drinking
water
assessment.
The
Drinking
Water
Level
of
Concern
(
DWLOC)
for
chronic
(
non­
cancer)
exposure
to
diflubenzuron
in
drinking
water
from
registered
and
proposed
uses
was
determined
as
694
ppb
for
the
U.
S.
population
(
total)
and
approximately
196
ppb
for
children
1­
2,
the
most
highly
exposed
population
sub­
group.
The
DWLOC
for
chronic
(
cancer)
exposure
to
CPU
in
drinking
water
was
determined
as
2.1
ppb
for
the
U.
S.
population
(
total).
The
estimated
maximum
concentrations
of
diflubenzuron
and
CPU
in
ground
and
surface
water
are
less
than
the
DWLOC's
as
a
contribution
to
chronic
aggregate
exposure.
2.
Non­
dietary
exposure.
Diflubenzuron
is
a
restricted
use
pesticide
based
on
its
toxicity
to
aquatic
invertebrates.
This
restricted
use
classification
makes
it
unavailable
for
use
by
homeowners.
Occupational
uses
of
diflubenzuron
may
expose
people
in
residential
locations,
parks,
or
forests
treated
with
diflubenzuron.
Based
on
very
low
residues
detected
in
forestry
dissipation
studies,
a
low
dermal
absorption
rate
(
0.5%),
and
extremely
low
dermal
and
inhalation
toxicity,
these
uses
are
expected
to
result
in
insignificant
risk,
and
are
therefore
not
included
in
the
aggregate
risk
assessment.

D.
Cumulative
Effects
The
registrant
has
considered
the
potential
for
cumulative
effects
of
diflubenzuron
and
other
substances
with
a
common
mechanism
of
toxicity.
The
mammalian
toxicity
of
diflubenzuron
is
well
defined.
We
are
not
aware
of
any
other
pesticide
product
registered
in
the
United
States
that
could
be
metabolized
to
p­
chloroaniline.
For
this
reason,
consideration
of
potential
cumulative
effects
of
residues
from
pesticidal
substances
with
a
common
mechanism
of
action
as
diflubenzuron
is
not
appropriate.
Thus,
only
the
potential
exposures
to
diflubenzuron
were
considered
in
the
total
exposure
assessment.

E.
Safety
Determination
1.
U.
S.
population.
Based
on
the
available
toxicology
and
exposure
database
for
diflubenzuron,
the
registrant
has
determined
that
the
total
non­
occupational
aggregate
exposure
from
diflubenzuron
would
occur
from
food
and
drinking
water
routes.
Based
on
the
0.02
mg/
kg/
day
RfD
(
reference
dose)
derived
from
the
dog
chronic
NOEL
of
2
mg/
kg/
day
and
a
100­
fold
safety
factor,
chronic
dietary
exposure
to
the
U.
S.
population
(
total)
is
0.9%
of
the
RfD.
Aggregate
exposure
does
not
exceed
100%
of
the
RfD
when
the
potential
theoretical
residues
in
drinking
water
are
included.

For
PCA,
the
total
non­
occupational
aggregate
exposure
would
occur
from
the
dietary
route.
The
risk
from
diflubenzuron­
derived
PCA
can
be
estimated
using
a
linear
extrapolation
of
the
dose­
response
from
the
rat
chronic
study
conducted
by
the
National
Toxicology
Program
in
which
rats
were
dosed
via
gavage
with
p­
chloroaniline
[
hydrochloride]
for
24
months.
EPA
has
determined
the
q1*
as
0.112
based
on
the
combined
incidence
of
liver
adenomas
and
carcinomas
in
male
mice.
Using
this
q1*,
the
theoretical
risk
to
the
U.
S.
population
(
total)
from
dietary
exposure
to
diflubenzuron­
derived
PCA
was
estimated
at
3.81
x
10­
7.

For
CPU,
total
aggregate
exposure
could
occur
from
food
and
drinking
water.
The
EPA
has
determined
that
since
CPU
is
structurally
related
to
Monuron
the
most
potent
Q1*
of
1.52
x
10­
2
(
based
on
male
rat
liver
neoplastic
nodule
and/
or
carcinoma
combined
tumor
rates)
from
the
NTP
carcinogenesis
data
for
Monuron
should
be
used
for
assessing
cancer
risk
from
CPU.
Using
this
Q1*
the
theoretical
risk
to
the
U.
S.
population
(
total)
from
dietary
exposure
to
CPU
was
estimated
at
8.53
x
10­
8.
The
aggregate
cancer
risk
including
drinking
water
does
not
exceed
the
level
of
concern.

2.
Infants
and
children.
The
dietary
exposure
of
diflubenzuron
was
calculated
as
0.000105
and
0.000225
mg/
kg/
day
respectively
for
nursing
and
non­
nursing
infants.
These
values
are
0.5%
and
1.1%
respectively
of
the
RfD
for
diflubenzuron.
The
dietary
exposure
from
diflubenzuron
in
children
3­
5
and
6­
12
years
old
was
determined
as
0.000299
mg/
kg/
day
and
0.000176
mg/
kg/
day,
respectively,
These
values
are
1.5%
and
0.9%
of
the
RfD,
respectively.
Aggregate
exposure
from
food
and
drinking
water
does
not
exceed
the
level
of
concern.
As
previously
discussed,
the
NOEL's
for
maternal
and
developmental
toxicity
in
rats
and
rabbits
were
greater
than
1,000
mg/
kg/
day,
and
the
NOEL
for
reproductive
toxicity
was
greater
than
5,000
mg/
kg/
day.
Therefore,
based
on
the
completeness
and
reliability
of
the
toxicity
data
and
the
conservative
exposure
assessment,
the
registrant
concludes
that
there
is
reasonable
certainty
that
no
harm
will
result
in
infants
and
children
from
aggregate
exposure
to
residues
of
diflubenzuron
and
its
conversion
products
containing
the
p­
chloroaniline
moiety.

F.
International
Tolerances
There
are
no
Codex,
Canadian,
or
Mexican
limits
for
residues
of
diflubenzuron
on
brassica
leafy
greens,
turnip
greens,
eggplant,
okra,
peanut,
barley,
oat,
wheat
or
pummelo.
