Document ID: EPA-HQ-OPP-2006-0024-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-04-12T04:00Z

FILE
NAME:
company.
wpt
(
7/
1/
2005)
(
xml)
Template
Number
P25
COMPANY
FEDERAL
REGISTER
DOCUMENT
SUBMISSION
TEMPLATE
(
1/
1/
2005)

EPA
Registration
Division
contact:
John
Bazuin,
(
703)
308­
7381
Syngenta
Crop
Protection,
Inc.

PP
9E5076,
8F4953,
0F6155,
and
6F4748
EPA
has
received
pesticide
petitions
PP
9E5076,
8F4953,
0F6155,
and
6F4748
from
Syngenta
Crop
Protection,
Inc.,
PO
Box
18300,
Greensboro,
NC
27419
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
by
establishing
tolerances
for
residues
of
difenoconazole
in
or
on
the
raw
agricultural
commodities
as
follows:
1.
PP
8F4953.
Cotton,
undelinted
seed
at
0.05
parts
per
million
(
ppm),
Cotton,
gin
byproducts
at
0.05
parts
per
million
(
ppm)
2.
PP
0F6155.
Corn,
sweet,
forage
at
0.01
parts
per
million
(
ppm),
Corn,
sweet,
stover
at
0.01
parts
per
million
(
ppm),
Corn,
sweet,
kernal
plus
cob
with
husks
removed
at
0.01
parts
per
million
(
ppm)

3.
PP
6F4748.
Barley,
hay
at
0.05
parts
per
million
(
ppm),
Barley,
straw
at
0.05
parts
per
million
(
ppm),
Barley,
forage
at
0.05
parts
per
million
(
ppm)

4.
PP
9E5076.
Proposes
the
establishment
of
an
import
tolerance
in
or
on
Grapes
at
0.1
parts
per
million
(
ppm),
and
pome
fruit
0.1
parts
per
million
(
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
residues
in
plants
is
understood
for
the
purpose
of
the
proposed
tolerance.
The
metabolism
of
14C­
difenoconazole
has
been
studied
using
both
phenyl
and
triazole
labels
in
wheat,
tomatoes,
potatoes,
grapes,
and
spring
rape.
The
metabolic
pathway
was
the
same
in
these
four
separate
and
distinct
crops.

2.
Analytical
method­
i.
Food.
Syngenta
Crop
Protection,
Inc.
has
submitted
a
practical
analytical
method
(
AG­
575B,
master
record
identification
(
MRID)
No.
428065­
04)
for
detecting
and
2
measuring
levels
of
difenoconazole
in
or
on
food
with
a
limit
of
quantitation
(
LOQ)
that
allows
monitoring
of
food
with
residues
at
or
above
the
levels
set
in
the
proposed
tolerances.
EPA
has
validated
this
method
and
copies
have
been
provided
to
FDA
for
insertion
into
pesticide
analytical
manual
(
PAM)
II.
The
method
is
available
to
anyone
who
is
interested,
and
may
be
obtained
from
the
Field
Operations
Division,
Office
of
Pesticide
Programs.

ii.
Livestock.
Syngenta
Crop
Protection,
Inc.
has
submitted
a
practical
analytical
method
(
AG­
544A,
MRID­
43292401)
for
detecting
and
measuring
levels
of
difenoconazole
in
or
on
cattle
tissues
and
milk
and
poultry
tissues
and
eggs,
with
a
LOQ
that
allows
monitoring
of
food
with
residues
at
or
above
the
levels
set
in
the
proposed
tolerances.
EPA
has
validated
this
method
and
copies
have
been
provided
to
FDA
for
insertion
into
PAM
II.
The
method
is
available
to
anyone
who
is
interested,
and
may
be
obtained
from
the
Field
Operations
Division,
Office
of
Pesticide
Programs.
Tolerances
in
meat,
milk,
poultry
or
eggs
were
established
for
enforcement
purposes.

3.
Magnitude
of
residues.
i.
Sweet
Corn.
Twelve
sweet
corn
and
three
popcorn
successful
field
trials
were
conducted
in
twelve
and
three
states
(
respectively)
in
typical
corn
growing
areas
in
the
United
States.
The
growing
regions
where
these
trials
were
conducted
collectively
represent
96%
and
95%
of
the
sweet
corn
and
popcorn,
respectively,
grown
in
the
United
States.
No
residues
of
difenoconazole
(<
0.01
ppm)
were
detected
in
any
sweet
corn
or
popcorn
substrates
in
this
study.

ii.
Cotton.
CGA­
169374
residues
found
on
the
17
cotton
samples
treated
at
a
rate
of
35
grams
a.
i./
100
kg
seed
(
350
ppm)
ranged
from
191
ppm
to
502
ppm,
illustrating
the
inherent
variation
of
the
seed
coating
process.
The
average
CGA­
169374
residues
found
on
the
1X
treated
seed
for
confirmatory
analysis
and
the
1X
treated
seed
for
storage
stability
were
323
ppm
and
336
ppm,
respectively.
This
indicates
acceptable
storage
stability
of
treated
seed,
prior
to
planting.

CGA­
169374
residues
found
on
the
4
samples
treated
at
a
3X
rate
of
105
grams
a.
i./
100
kg
seed
(
1050
ppm)
ranged
from
963
ppm
to
1565
ppm
and
further
elucidate
the
inherent
variation
of
the
seed
coating
process.
The
average
CGA­
169374
residue
found
on
the
3X
treated
seed
was
1216
ppm.

No
residues
(<
0.05
ppm)
of
CGA­
169374
were
detected
in
cotton
field
trash
or
cotton
processing
fractions
at
either
treatment
rate.

iii.
Barley.
Nine
barley
trials
were
conducted
in
eight
states.
Fifty­
four
1X
treated
grain,
hay,
and
straw
samples
(
fed
commodities)
were
analyzed.
In
addition,
18
1X
treated
forage
samples
were
analyzed.

Residues
of
difenoconazole
in
barley
grown
from
seed
treated
with
difenoconazole
were
below
the
LOQ
in
forage,
hay
and
straw
(<
0.05
ppm)
and
grain
(<
0.01
ppm).

iv.
Grapes
(
Import
Tolerance).
Data
have
been
provided
from
thirty
two
grape
residue
trials
3
conducted
in
France,
Chile,
South
Africa,
Italy,
and
Spain.
Score
®
and
Slick
®
are
registered
for
use
in
France
and
Switzerland,
respectively.
The
maximum
rate
for
any
country
is
50
grams
a.
i./
ha.
Up
to
3
applications
can
be
made
at
this
rate.
The
maximum
rate
in
France
is
30
grams
a.
i./
ha.
At
this
rate,
up
to
4
applications
can
be
made.
The
total
amounts
applied
ranged
from
120
to
480
grams
a.
i./
ha
to
cover
specific
country
labels
and
to
collect
data
at
exaggerated
doses.
Data
were
generated
on
transfer
of
residues
to
grape
juice
and
wine
from
12
and
13
samples,
respectively.
Grape
pomace
data
were
generated
from
17
samples.
Six
residue
decline
curves
were
produced.

The
results
of
these
studies
show
that
the
use
of
difenoconazole
as
a
foliar
treatment
to
grapes
results
in
low
(<
0.1
ppm)
residues
in
whole
fruit
at
harvest
and
no
detectable
residues
in
the
processed
commodities
grape
juice
or
wine.

v.
Pome
Fruit
(
Import
Tolerance).
Data
have
been
provided
from
forty
seven
field
residue
trials
conducted
with
apples
and
nine
field
trials
conducted
on
pears.
Trials
were
conducted
in
Germany,
Chile,
South
Africa,
New
Zealand,
Australia,
Switzerland,
and
Brazil.
The
maximum
use
rates
range
from
30
to
87.5
grams
active
ingredient/
ha/
application,
spraying
to
run
off.
Total
amounts
that
can
be
applied
per
season
range
from
120
to
455
grams
a.
i./
ha.

At
harvest
residues
of
difenoconazole
in
apples
(
whole
fruit)
ranged
from
0.02
ppm
to
0.08
ppm
and
from
0.03
ppm
to
0.10
ppm
in
pears
in
studies
conducted
under
maximum
label
conditions.
Whole
fruit
residues
declined
rapidly
with
time.
No
residues
(<
0.02
ppm)
were
found
in
apple
juice
regardless
of
the
treatment
(
even
up
to
4X
the
use
rate
for
each
country).
Residues
did
not
concentrate
in
applesauce
or
in
preserved
pears.
Slight
concentration
(
1.8X)
was
observed
in
dried
apple
slices,
while
dried
pears
showed
no
detectable
residues.
Difenoconazole
residues
concentrated
in
apple
pomace(
4X).
The
use
of
difenoconazole
as
a
foliar
treatment
to
pome
fruit
results
in
low
(
0.1
ppm
or
less)
residues
in
whole
fruit
at
harvest
and
no
detectable
residues
in
the
processed
commodities
apple
juice,
applesauce,
or
preserved
pears.
Trace
residues
(<
0.02
ppm
to
0.11
ppm)
were
found
in
dried
fruit.

vi.
Livestock.
The
worst
case
theoretical
dietary
burden
for
either
beef
or
dairy
cattle,
when
sweet
corn,
cotton,
and
cereal
commodities
are
fed
results
in
residues
below
the
limit
of
detection
(<
0.05
ppm).
Extrapolated
CGA­
169374
residues
based
on
the
maximum
cotton,
sweet
corn,
and
cereal
commodities,
and
dairy
cattle
residue
values
representing
the
maximum
cattle
exposure
and
subsequent
cattle
residues
demonstrate
that
feeding
difenoconazole
commodities
to
beef
or
dairy
cattle
will
not
result
in
residues
in
tissues
or
milk
above
established
tolerances.

No
sweet
corn
commodities
are
fed
to
poultry.
Contribution
to
poultry
diet
from
meal
from
CGA­
169374
treated
cotton
and
/
or
other
commodities
with
established
or
proposed
difenoconazole
uses
would
be
negligible
(<
0.05
ppm).
Extrapolated
CGA­
169374
residues
based
on
the
maximum
grain
and
poultry
residue
values
representing
the
maximum
poultry
exposure
and
subsequent
poultry
residues
demonstrate
that
proposed
difenoconazole
uses
will
not
result
in
residues
in
tissues
or
eggs
above
established
tolerances.]
4
B.
Toxicological
Profile
1.
Acute
toxicity.
Difenoconazole
has
a
low
order
of
acute
toxicity.
The
oral
rat
LD
50
is
1,453
milligram/
kilogram
(
mg/
kg).
The
rabbit
acute
dermal
LD
50
is
>
2,010
mg/
kg
and
the
rat
inhalation
LC
50
is
>
3.285
milligrams
per
liter
(
mg/
L).
Difenoconazole
is
not
a
skin
sensitizer
in
guinea
pig
and
shows
slight
eye
and
dermal
irritation
in
the
rabbit.

2.
Genotoxicty.
There
was
no
evidence
of
the
induction
of
point
mutations
in
an
Ames
test,
no
evidence
of
mutagenic
effects
in
a
mouse
lymphoma
test
or
in
a
nucleus
anomaly
test
with
Chinese
hamsters,
and
no
evidence
of
induction
of
DNA
damage
in
a
rat
hepatocyte
DNA
repair
test
or
in
a
human
fibroblast
DNA
repair
test.

3.
Reproductive
and
developmental
toxicity.
An
oral
teratology
study
in
rats
had
a
maternal
no­
observed
adverse
effect
level
(
NOAEL)
of
16
mg/
kg/
day
based
on
excess
salivation
and
decreased
body
weight
gain
and
food
consumption.
The
developmental
NOAEL
of
85
mg/
kg/
day
was
based
on
effects
seen
secondary
to
maternal
toxicity
including
slightly
reduced
fetal
body
weight
and
minor
changes
in
skeletal
ossification.
An
oral
teratology
study
in
rabbits
had
a
maternal
NOAEL
of
25
mg/
kg/
day
based
on
decreased
body
weight
gain,
death,
and
abortion.
The
developmental
NOAEL
of
25
mg/
kg/
day
was
based
on
effects
seen
secondary
to
maternal
toxicity
including
a
slight
increase
in
post­
implantation
loss
and
resorptions,
and
decreased
fetal
weight.
A
2­
generation
reproduction
study
in
rats
had
a
parental
and
reproductive
NOAEL
of
25
part
per
million
(
ppm)
based
on
significantly
reduced
female
body
weight
gain,
and
reductions
in
male
pup
weights
at
21­
days.

4.
Subchronic
toxicity.
A
13­
week
rat
feeding
study
identified
liver
as
a
target
organ
and
had
a
NOAEL
of
20
ppm.
A
13­
week
mouse
feeding
study
also
identified
liver
as
a
target
organ
and
had
a
NOAEL
of
20
ppm.
A
26­
week
dog
feeding
study
further
identified
liver,
and
also
the
eyes,
as
target
organs
and
had
a
NOAEL
of
100
ppm.
A
21­
day
dermal
study
in
rabbits
had
a
NOAEL
of
10
mg/
kg/
day
based
on
decreased
body
weight
gain
at
100
and
1,000
mg/
kg/
day.

5.
Chronic
toxicity.
A
24­
month
feeding
study
in
rats
had
a
NOAEL
of
20
ppm
based
on
liver
toxicity
at
500
and
2,500
ppm.
An
18­
month
mouse
feeding
study
had
an
overall
NOAEL
of
30
ppm
based
on
decreased
body
weight
gain
and
liver
toxicity
at
300
ppm.
A
12­
month
feeding
study
in
dogs
had
a
NOAEL
of
100
ppm
based
on
decreased
food
consumption
and
increased
alkaline
phosphatase
levels
at
500
ppm.

6.
Animal
metabolism.
The
metabolism
of
difenoconazole
is
well
understood.
Studies
with
14C­
difenoconazole
in
the
rat,
goat,
and
hen
demonstrate
that
the
majority
of
the
administered
dose
5
(
76
to
>
98%)
is
eliminated
via
the
excreta
as
parent
and
metabolites.
Very
low
concentrations
of
radioactivity,
accounting
for
<
1
to
4%
of
the
applied
dose,
remain
in
tissues.
The
liver
and
kidney
typically
show
the
highest
radioactivity,
but
in
the
rat,
the
highest
concentration
in
any
tissue
was
found
in
the
fat.
Concentrations
in
goat
milk
reached
a
plateau
on
day
6
of
the
study
at
0.043
ppm
for
the
triazole
label
and
0.007
ppm
for
the
phenyl
label
when
goats
were
fed
approximately
5
ppm
for
10
days.
Similarly,
very
little
radioactivity
was
deposited
in
eggs;
radioactivity
reached
a
plateau
of
0.248
to
0.299
ppm
in
yolks
after
7
to
8­
days,
and
0.007
to
0.153
ppm
in
whites
after
5
days,
in
hens
fed
at
a
rate
equivalent
to
5
ppm
in
the
diet
for
14
consecutive
days.
CGA­
205375,
an
alcohol
resulting
from
the
deketalization
of
the
dioxolane
ring
of
difenoconazole,
is
a
major
metabolite
found
in
animal
tissues,
excreta,
milk,
and
eggs.
The
presence
of
CGA­
71019,
containing
only
the
triazole
ring,
and
CGA­
189138,
containing
only
the
phenyl
ring,
indicates
that
bridge
cleavage
can
occur
in
animals
as
well
as
plants.
The
metabolite
patterns
in
the
excreta
of
hens,
goats,
and
rats
were
similar.

7.
Metabolite
toxicology.
The
residue
of
concern
for
tolerance
setting
purposes
is
the
parent
compound.
Metabolites
of
difenoconazole
are
considered
to
be
of
equal
or
lesser
toxicity
than
the
parent.

8.
Endocrine
disruption.
Developmental
toxicity
studies
in
rats
and
rabbits
and
a
2­
generation
reproduction
study
in
rats
gave
no
specific
indication
that
difenoconazole
may
have
effects
on
the
endocrine
system
with
regard
to
development
or
reproduction.
Furthermore,
histologic
investigations
were
conducted
on
endocrine
organs
(
thyroid,
adrenal,
and
pituitary,
as
well
as
endocrine
sex
organs)
from
long­
term
studies
in
dogs,
rats,
and
mice.
There
was
no
indication
that
the
endocrine
system
was
targeted
by
difenoconazole,
even
when
animals
were
treated
with
maximally
tolerated
doses
over
the
majority
of
their
lifetime.
Difenoconazole
has
not
been
found
in
RAC
at
the
LOQ.
Based
on
the
available
toxicity
information
and
the
lack
of
detected
residues,
it
is
concluded
that
difenoconazole
has
no
potential
for
interfering
with
the
endocrine
system,
and
there
is
no
risk
of
endocrine
disruption
in
humans.

C.
Aggregate
Exposure
1.
Dietary
exposure.
Tier
III/
IV
chronic
and
acute
dietary
exposure
evaluations
were
made
for
difenoconazole
using
the
Dietary
Exposure
Evaluation
Model
(
DEEM­
FCIDTM),
version
2.03
from
Exponent.
These
exposure
assessments
included
all
registered
and
proposed
uses.
Registered
uses
included
foliar
treatments
on
imported
bananas,
and
seed
treatments
on
canola,
wheat,
imported
barley
grain,
imported
rye
grain,
and
a
Section
18
seed
treatment
use
on
sweet
corn.
Proposed
uses
include
a
seed
treatment
use
on
cotton
and
foliar
treated
imported
grapes
and
pome
fruit.
Market
basket
monitoring
data
were
utilized
for
bananas,
milk,
and
wheat
flour
(
Syngenta
Study
1102
99,
MRID
45917401);
magnitude
of
residue
data
from
supervised
field
trials
were
utilized
for
all
other
crops.
Residue
trials
were
conducted
at
the
maximum
labeled
treatment
rate
and
harvested
at
the
6
minimum
pre­
harvest
interval
(
PHI)
to
obtain
maximum
expected
residues.
Experimental
processing
factors
were
used
for
apple
juice
(
0.67x),
apple
sauce
(
0.17x),
dried
bananas
(
3.90x),
dried
beef
(
1.92x),
grape
juice
(
0.365x),
and
raisins
(
1.969x);
all
other
processing
factors
used
DEEM
 
(
version
7.87)
default
processing
values.
Anticipated
residues
in
meat,
milk,
and
eggs
were
calculated
by
constructing
a
theoretical
worst­
case
diet,
consisting
of
a
nutritionally
balanced
mixture
of
feeds
(
typically
30%
protein
and
70%
carbohydrates).
Drinking
water
estimates
were
selected
using
the
higher
of
the
estimated
drinking
water
concentrations
(
EDWCs)
for
surface
and
ground
water.
All
consumption
data
for
these
assessments
were
taken
from
the
USDA's
Continuing
Survey
of
Food
Intake
by
individuals
(
CSFII)
with
the
1994­
96
consumption
database
and
the
Supplemental
CSFII
children's
survey
(
1998)
consumption
database.

i.
Food.
Acute
Exposure.
The
difenoconazole
acute
dietary
(
food
only)
risk
assessment
was
performed
for
all
population
subgroups
using
an
acute
reference
dose
of
0.25
mg/
kg­
bw/
day
based
upon
a
developmental
toxicity
study
in
rabbits
with
a
no
observable
adverse
effect
level
(
NOAEL)
of
25
mg/
kg­
bw/
day
and
an
uncertainty
factor
of
100X.
The
100X
safety
factor
includes
intra­
and
inter­
species
variations.
No
additional
FQPA
safety
factor
was
applied.
For
the
purpose
of
aggregate
risk
assessment,
the
exposure
values
were
expressed
in
terms
of
margin
of
exposure
(
MOE),
which
was
calculated
by
dividing
the
NOAEL
by
the
exposure
for
each
population
subgroup.
In
addition,
exposure
was
expressed
as
a
percent
of
the
acute
reference
dose
(%
aRfD).
Acute
(
food
only)
exposure
to
the
U.
S.
population
resulted
in
a
MOE
of
19,557
(
0.51%
of
the
aRfD
of
0.25
mg/
kg­
bw/
day).
The
most
exposed
sub­
population
was
children
(
1­
2
years
old)
with
a
MOE
of
9,426
(
1.06%
of
the
aRfD
of
0.25
mg/
kg­
bw/
day).
Since
the
benchmark
MOE
for
this
assessment
was
100
and
since
the
EPA
generally
has
no
concern
for
exposures
below
100%
of
the
aRfD,
Syngenta
believes
that
there
is
a
reasonable
certainty
that
no
harm
will
result
from
dietary
(
food
only)
exposure
to
residues
arising
from
the
current
and
proposed
uses
for
difenoconazole.

Chronic
Exposure.
The
difenoconazole
chronic
dietary
(
food
only)
risk
assessment
was
performed
for
all
population
subgroups
using
a
chronic
reference
dose
of
0.01
mg/
kg­
bw/
day
based
upon
a
2­
year
chronic
feeding/
oncogenicity
study
in
rats
with
a
no
observable
adverse
effect
level
(
NOAEL)
of
1.00
mg/
kg­
bw/
day
and
an
uncertainty
factor
of
100X.
The
100X
safety
factor
includes
intra­
and
inter­
species
variations.
No
additional
FQPA
safety
factor
was
applied.
For
the
purpose
of
aggregate
risk
assessment,
the
exposure
values
were
expressed
in
terms
of
margin
of
exposure
(
MOE),
which
was
calculated
by
dividing
the
NOAEL
by
the
exposure
for
each
population
subgroup.
In
addition,
exposure
was
expressed
as
a
percent
of
the
chronic
reference
dose
(%
RfD).
Chronic
(
food
only)
exposure
to
the
U.
S.
population
resulted
in
a
MOE
of
32,813
(
0.3%
of
the
RfD
of
0.01
mg/
kg­
bw/
day).
The
most
exposed
sub­
population
was
children
(
1­
2
years
old)
with
a
MOE
of
5,685
(
1.8%
of
the
RfD
of
0.01
mg/
kg­
bw/
day).
Since
the
benchmark
MOE
for
this
assessment
was
100
and
since
the
EPA
generally
has
no
concern
for
exposures
below
100%
of
the
RfD,
Syngenta
believes
that
there
is
a
reasonable
certainty
that
no
harm
will
result
from
dietary
(
food
only)
exposure
to
residues
arising
from
the
current
and
proposed
uses
for
difenoconazole.

Cancer.
A
quantitative
risk
assessment
using
a
cancer
endpoint
was
not
performed.
7
ii.
Drinking
water.
The
EPA
uses
the
Pesticide
Root
Zone/
Exposure
Analysis
Modeling
System
(
PRZM/
EXAMS)
to
estimate
pesticide
concentrations
in
surface
water
and
SCI­
GROW
to
predict
pesticide
concentrations
in
ground
water.
None
of
these
models
include
the
impact
of
processing
raw
water
(
mixing,
dilution,
or
treatment)
prior
to
distribution
as
drinking
water.
The
primary
use
of
these
models
by
the
Agency
is
to
provide
a
conservative
approximation
of
the
estimated
environmental
concentration
of
specific
pesticides
in
drinking
water.
The
highest
use
rate
for
any
current
or
pending
crop
use,
adjusted
for
percent
crop
area
(
PCA),
for
difenoconazole
in
the
United
States
is
a
seed
treatment
use
on
canola.
This
use
was
used
to
assess
the
potential
environmental
exposure
to
drinking
water.
For
ground
water
(
SCI­
GROW)
modeling,
Syngenta
has
determined
an
Estimated
Drinking
Water
Concentration
(
EDWC)
of
difenoconazole
at
the
highest
use
rate
(
0.036
lb
a.
i./
A
x
1
application,
seed
treatment)
of
0.00129
ppb.
Using
the
same
difenoconazole
seed
treatment
use
rate
for
surface
water
modeling
(
PRZM/
EXAMS),
the
acute
EDWC
was
0.475
ppb
and
the
chronic
(
non­
cancer,
annual
average)
EDWCs
was
0.330
ppb.
Since
the
surface
water
EDWCs
exceed
the
ground
water
EDWC,
the
PRZM/
EXAMS
surface
water
values
were
used
for
comparison
purposes
and
will
be
considered
protective
for
any
ground
water
concentration
concerns.

Acute
Exposure
from
Drinking
Water:
The
acute
EDWC
of
0.475
ppb
was
used
to
calculate
the
acute
drinking
water
exposure
values
for
the
U.
S.
Population
and
population
subgroups.
The
drinking
water
exposures
were
calculated
with
the
following
assumptions:
adult
males
and
general
population
(
70
kg)
with
a
consumption
of
2
liters
water
per
day,
adult
females
(
60
kg)
with
a
consumption
of
2
liters
water
per
day,
and
infants
and
all
children
<
13
years
old
(
10
kg)
with
a
consumption
of
1
liter
water
per
day.
Acute
drinking
water
exposure
to
the
U.
S.
population
resulted
in
a
MOE
of
<
1,000,000
(<
0.1%
of
the
aRfD
of
0.25
mg/
kg­
bw/
day).
Acute
drinking
water
exposure
to
the
most
sensitive
subpopulation
(
children
1­
2
years
old)
resulted
in
a
MOE
of
520,833
(<
0.1%
of
the
acute
RfD
of
0.25
mg/
kg­
bw/
day).
Since
the
benchmark
MOE
for
this
assessment
is
100
and
since
the
EPA
generally
has
no
concern
for
exposures
below
100%
of
the
aRfD,
Syngenta
believes
that
there
is
a
reasonable
certainty
that
no
harm
will
result
from
acute
dietary
(
drinking
water)
exposure
to
residues
arising
from
the
current
and
proposed
uses
for
difenoconazole.

Chronic
Exposure
from
Drinking
Water.
The
chronic
water
exposure
was
obtained
from
the
DEEM­
FCID
 
software
based
on
an
input
of
the
annual
average
surface
water
EDWC
of
0.330
ppb
for
water,
direct
and
indirect,
all
sources.
Chronic
drinking
water
exposure
to
the
U.
S.
population
resulted
in
a
MOE
of
143,769
(
0.1%
of
the
RfD
of
0.01
mg/
kg­
bw/
day).
Chronic
drinking
water
exposure
to
the
most
sensitive
subpopulation
(
all
infants
<
1
year
old)
resulted
in
a
MOE
of
43,852
(
0.2%
of
the
chronic
RfD
of
0.01
mg/
kg­
bw/
day).
Since
the
benchmark
MOE
for
this
assessment
was
100
and
since
the
EPA
generally
has
no
concern
for
exposures
below
100%
of
the
RfD,
Syngenta
believes
that
there
is
a
reasonable
certainty
that
no
harm
will
result
from
chronic
dietary
(
drinking
water)
exposure
to
residues
arising
from
the
current
and
proposed
uses
for
difenoconazole.
8
2.
Non­
dietary
exposure.
There
are
no
current
or
proposed
uses
of
difenoconazole
that
would
result
in
residential
exposure
D.
Cumulative
Effects
Cumulative
Exposure
to
Substances
with
a
Common
Mechanism
of
Toxicity.
Section
408(
b)(
2)(
D)(
v)
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".
The
EPA
does
not
have,
at
this
time,
available
data
to
determine
whether
difenoconazole
has
a
common
mechanism
of
toxicity
with
other
substances
or
how
to
include
this
pesticide
in
a
cumulative
risk
assessment.
For
the
purposes
of
this
tolerance
action,
the
EPA
has
not
assumed
that
difenoconazole
has
a
common
mechanism
of
toxicity
with
other
substances.

E.
Safety
Determination
1.
U.
S.
population.
Using
the
conservative
assumptions
described
above,
and
based
on
the
completeness
and
reliability
of
the
toxicity
data,
the
acute
aggregate
(
food
plus
water)
exposure
calculation
for
current
and
proposed
uses
of
difenoconazole
provided
a
MOE
of
19,345
for
the
U.
S.
population.
The
chronic
aggregate
exposure
analysis
(
food
and
water)
showed
that
exposure
from
all
current
and
proposed
difenoconazole
uses
resulted
in
a
MOE
of
26,716
for
the
U.
S.
population.
Since
the
worst
case
aggregate
MOE
of
19,345
(
acute
aggregate
exposure)
exceeds
the
benchmark
MOE
of
100,
Syngenta
believes
that
there
is
a
reasonable
certainty
that
no
harm
will
occur
to
the
U.
S.
Population
from
chronic
and
acute
aggregate
exposures
arising
from
all
current
and
proposed
uses
for
difenoconazole.

2.
Infants
and
children.
Using
the
conservative
assumptions
described
above,
and
based
on
the
completeness
and
reliability
of
the
toxicity
data,
the
acute
aggregate
(
food
plus
water)
exposure
calculation
for
current
and
proposed
uses
of
difenoconazole
provided
a
MOE
of
9,258
for
children
1­
2
years
old.
The
chronic
aggregate
exposure
analysis
(
food
and
water)
showed
that
exposure
from
all
current
and
proposed
difenoconazole
uses
resulted
in
a
MOE
of
5,370
for
children
1­
2
years
old.
Since
the
worst
case
aggregate
MOE
of
5,370
(
chronic
aggregate
exposure)
exceeds
the
benchmark
MOE
of
100,
Syngenta
believes
that
there
is
a
reasonable
certainty
that
no
harm
will
occur
to
infants
and
children
from
chronic
and
acute
aggregate
exposures
arising
from
all
current
and
proposed
uses
for
difenoconazole.

F.
International
Tolerances
There
are
no
Codex
maximum
residue
levels
(
MRLs)
established
for
residues
of
difenoconazole
in
any
commodity.
In
Canada,
MRLs
have
been
established
for
residues
of
difenoconazole
in
barley
(
0.01
ppm),
canola/
rapeseed
(
0.03
ppm),
eggs
(
0.05
ppm),
corn
grain,
field
(
0.01
ppm),
meat
and
meat
by­
products
of
cattle,
goats,
hogs,
poultry
and
sheep
(
0.05
ppm),
milk
(
0.01
ppm),
mustard
seed
(
0.05
ppm),
and
wheat
(
0.1
ppm).
Mexico
relies
upon
current
U.
S.
9
tolerances
and
has
not
established
national
MRLs
for
difenoconazole
in
any
commodity.

In
the
United
States,
tolerances
have
been
established
for
residues
of
difenoconazole
in
bananas,
imported
(
0.2
ppm),
barley
(
0.1
ppm),
eggs
(
0.05
ppm),
meat
and
meat
by­
products
of
cattle,
goats,
hogs,
poultry
and
sheep
(
0.05
ppm),
milk
(
0.01
ppm),
rye
(
0.1
ppm),
and
wheat
(
0.1
ppm).
When
established
U.
S.
tolerances
are
compared
to
Canadian
MRLs,
a
3X
difference
is
observed
in
canola
(
0.03
ppm
Canada,
0.01
ppm
US)
and
a
10X
difference
is
observed
in
barley
(
0.10
ppm
US,
0.01
ppm
Canada).