Document ID: EPA-HQ-OPP-2006-0324-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-05-10T04:00Z

FILE
NAME:
company.
wpt
(
7/
1/
2004)

ATTENTION:
All
commodity
terms
must
comply
with
the
Food
and
Feed
Commodity
Vocabulary
database
(
http://
www.
epa.
gov/
pesticides/
foodfeed/).

COMPANY
FEDERAL
REGISTER
DOCUMENT
SUBMISSION
TEMPLATE
(
7/
1/
2004)

EPA
Registration
Division
contact:
[
Janet
Whitehurst,
(
703)
305­
6129]

INSTRUCTIONS:
Please
utilize
this
outline
in
preparing
tolerance
petition
documents.
In
cases
where
the
outline
element
does
not
apply
please
insert
"
NA­
Remove"
and
maintain
the
outline.
The
comment
notes
that
appear
on
the
left
margin
represent
hidden
typesetting
codes
designed
to
expedite
the
processing
of
the
Federal
Register
document.
Please
do
not
remove
or
alter
these
comment
notes
or
change
the
margins,
font,
or
format
in
your
document.
Simply
replace
the
instructions
that
appear
in
italics
and
brackets,
i.
e.,
"[
insert
company
name],"
with
the
information
specific
to
your
action.

[
7969­
pending]

Summary
of
Petitions
EPA
has
received
a
pesticide
petition
([
7969­
pending])
from
[
BASF
Corporation],
[
26
Davis
Drive,
P.
O.
Box
13528,
Research
Triangle
Park,
NC
27709]
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.

Options
(
pick
one)

1.
by
establishing
a
tolerance
for
residues
of
[(
3­
bromo­
6­
methoxy­
2­
methylphenyl)(
2,3,4­
trimethoxy­
6­
methylphenyl)
methanone]
in
or
on
the
raw
agricultural
commodity
[
table
and
wine
grapes]
at
[
0.5]
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.
2
A.
Residue
Chemistry
1.
Plant
metabolism.
[
In
plant
metabolism
studies
conducted
in
grapevines
with
BAS
560
F,
the
parent
compound
was
the
principal
residue
in
grapes.
BAS
560
F
is
metabolized
through
methyl
and
ring
oxidative
biotransformations,
followed
by
enzymatic
glucoside
conjugation
reactions
to
yield
the
conjugates
from
their
corresponding
aglycons.
All
major
metabolites,
which
were
present
at
very
low
levels,
are
considered
non­
relevant
as
all
were
detected
in
the
rat
metabolism
study
as
aglycons
or
conjugates,
and
can
therefore
be
considered
as
not
toxicologically
significant.
Thus,
only
parent
BAS
560
F
is
considered
relevant
to
define
the
residue
in
plants.

The
results
from
a
hydrolysis
study
designed
to
simulate
different
industrial
and
household
processes
(
pasteurization,
brewing,
boiling
and
sterilization)
showed
that
BAS
560
F
is
stable.
Therefore,
BAS
560
F
as
unchanged
parent
is
proposed
as
the
relevant
residue
in
grapes
and
industrial
or
household
preparations
of
grapes.]

2.
Analytical
method.
[
BASF
Analytical
Methods
No.
FAMS
105­
01
"
CL
375839:
Analytical
Method
for
the
Determination
of
the
Active
Ingredient
in
Grapes"
and
No.
FAMS
106­
01
"
CL
375839:
Analytical
Method
for
the
Determination
of
the
Active
Ingredient
in
Must
and
Wine"
were
developed
to
determine
residues
of
BAS
560
F
in
grapes
and
wine,
respectively.
In
Method
FAMS
105­
01,
BAS
560
F
residues
are
extracted
from
the
sample
with
n­
heptane
/
acetone
8
/
2
(
v/
v).
This
is
followed
by
liquid
/
liquid
partition
with
ethyl
acetate
/
water
to
remove
sugar
coextractives
and
the
organic
phase
is
then
dried
with
sodium
sulfate.
The
extract
is
subjected
to
further
clean
up
using
high
performance
liquid
chromatography.
Quantitative
determination
of
BAS
560
F
is
carried
out
by
capillary
gas
chromatography
with
an
electron
capture
detector
(
GC/
ECD).

In
Method
FAMS
106­
1,
BAS
560
F
residues
are
extracted
from
the
sample
by
means
of
an
Extrelut
cartridge
(
Extrelut
NT
20,
pre­
packed
columns
for
extraction
of
lipophilic
compounds
from
aqueous
solutions).
The
extract
is
subjected
to
further
clean
up
using
high
performance
liquid
chromatography.
Quantitative
determination
of
BAS
560
F
is
carried
out
by
capillary
gas
chromatography
with
an
electron
capture
detector
(
GC/
ECD).
An
independent
laboratory
validation
demonstrated
good
performance
of
these
methods.]

3.
Magnitude
of
residues.
[
A
total
of
14
crop
residue
trials
were
conducted
in
representative
vine
growing
areas
in
Northern
and
Southern
Europe;
6
trials
generated
7
results
in
Northern
Europe
and
8
trials
generated
11
results
in
Southern
Europe
(
duplicate
samples
were
taken
from
some
of
the
at­
harvest
residue
trials).
Trials
were
performed
in
Northern
and
Southern
France,
Germany,
Italy
and
Spain
in
1999
and
2000.

In
all
trials,
a
500
g/
L
suspension
concentrate
formulation
of
BAS
560
F
(
designated
BAS
560
01
F)
was
applied
eight
times
at
approximate
weekly
intervals,
at
a
target
application
rate
of
100
g
a.
i./
ha.
At
two
sites
in
Germany
and
Italy,
dose
rates
applied
to
the
vines
were
marginally
3
higher
due
to
differing
viticulture
practices
in
these
countries.
In
Germany
and
Italy,
dose
rates
applied
to
the
vines
are
dependent
upon
the
plant
size;
with
time
the
applied
dose
increases,
but
as
the
surface
area
of
the
fruit
is
also
increasing
the
applied
concentration
remains
relatively
constant.
It
is
therefore
considered
appropriate
to
include
results
from
these
sites
to
determine
the
proposed
tolerance.

In
decline
curve
trials,
fruit
samples
were
taken
directly
before
and
after
the
last
application,
and
at
approximately
7
day
intervals
up
to
48
days
after
the
final
(
i.
e.,
eighth)
application.

Residues
in
the
raw
agricultural
commodity
consisted
of
parent
BAS
560
F
only.
Detectable
residues
were
recorded
immediately
after
the
last
application.
For
Northern
Europe,
initial
residue
levels
ranged
from
0.24
mg/
kg
to
0.37
mg/
kg,
declining
to
0.10
mg/
kg
to
0.19
mg/
kg
by
the
proposed
post
harvest
interval
(
PHI)
(
28
days
after
the
final
application).
For
Southern
Europe,
initial
residue
levels
ranged
from
0.38
mg/
kg
to
0.54
mg/
kg,
declining
to
0.07
mg/
kg
to
0.30
mg/
kg
by
the
proposed
PHI
(
28
days
after
the
final
application).

A
comparison
of
data
from
Northern
and
Southern
European
trials
demonstrate
that
the
residue
levels
were
comparable
in
the
two
regions.
The
mean
residue
level
in
Northern
Europe
(
0.15
mg/
kg;
0.10
 
0.19
mg/
kg)
was
very
similar
to
that
in
Southern
Europe
(
0.17
mg/
kg;
0.07
 
0.30
mg/
kg).

The
results
from
processing
studies
demonstrated
the
absence
of
detectable
residues
(
LOQ
=
0.05
mg/
kg)
in
wine
or
in
raisins
following
processing
of
treated
grapes.

Since
grape
vines
are
a
permanent
crop,
no
confined
or
field
rotation
studies
are
needed
to
support
this
petition.]

B.
Toxicological
Profile
1.
Acute
toxicity.
[
In
an
acute
toxicity
study
with
rats,
BAS
560
F
was
practically
non­
toxic
(
EPA
Tox.
Category
IV).
In
an
acute
neurotoxicity
study
with
rats,
no
signs
of
neurotoxicity
were
detected
up
to
2,000
mg/
kg
b.
w.,
the
highest
dose
tested.]

2.
Genotoxicty.
[
BAS
560
F
was
evaluated
for
its
potential
genotoxicity
in
vitro
using
bacterial
and
mammalian
cell
mutagenicity
tests
and
a
chromosome
damage
(
clastogenicity)
test.
The
results
of
these
studies
demonstrated
the
absence
of
a
genotoxic
effect.
In
vivo,
the
test
substance
was
assessed
for
the
induction
of
micronuclei
in
mice.
The
result
of
this
study
showed
that
BAS
560
F
has
no
chromosome­
damaging
potential.
4
It
is
therefore
concluded,
that
BAS
560
F
has
no
mutagenic
or
genotoxic
properties
both
in
vitro
and
in
vivo.]

3.
Reproductive
and
developmental
toxicity.
[
The
reproductive
and
developmental
toxicity
of
BAS
560
F
was
investigated
in
a
2­
generation
reproduction
study
in
rats
as
well
as
in
prenatal
toxicity
studies
in
rats
and
rabbits.

In
the
definitive
2­
generation
reproduction
study
in
rats,
the
NOAEL
for
fertility
and
reproduction
was
10,000
ppm
(
the
highest
concentration
tested),
equivalent
to
approximately
811
mg/
kg
b.
w./
day
based
on
food
consumption
data
during
the
premating
periods.
The
parental
NOAEL
of
BAS
560
F
is
500
ppm
(
approximately
39
mg/
kg
b.
w./
day
based
on
food
consumption
data).
The
1,000
ppm
treatment
showed
statistically
significant
decreases
in
body
weight
and
weight
gain
in
F1
parental
males
and
increased
absolute
and
relative
liver
weights
in
females.
The
NOAEL
for
pup
(
offspring)
toxicity
was
1,000
ppm
(
approximately
79
mg/
kg
b.
w./
day
based
on
food
consumption
data);
the
10,000
ppm
treatment
showed
a
statistically
significant
decrease
in
pup
body
weight
(
31%)
during
lactation,
an
increase
in
relative
liver
weights
at
weaning,
and
a
delay
in
vaginal
opening
(
F1
only).

In
the
prenatal
toxicity
study
in
rats,
there
was
no
treatment­
related
maternal
or
developmental
toxicity
observed,
even
at
the
highest
dose
tested
(
1,000
mg/
kg
b.
w./
day).
On
the
basis
of
these
data,
the
maternal
NOAEL
of
BAS
560
F
is
1,000
mg/
kg
b.
w./
day
(
highest
dose
tested).
The
1,000
mg/
kg
b.
w./
day
dose
showed
a
statistically
significantly
increased
ratio
of
liver
weight
to
terminal
body
weights.
However,
no
correlating
microscopic
changes
were
diagnosed,
indicating
that
the
increased
relative
liver
weight
was
not
considered
toxicologically
significant.
The
developmental
NOAEL
for
BAS
560
F
is
1,000
mg/
kg
b.
w./
day
(
no
effects
were
observed
at
the
highest
dose
tested).
Based
on
the
above
results,
BAS
560
F
is
not
selectively
toxic
to
the
fetus.
In
addition,
BAS
560
F
was
not
teratogenic
in
rats.

In
the
rabbit
prenatal
toxicity
study,
developmental
toxicity
was
observed
in
the
presence
of
maternal
toxicity.
Specifically,
the
maternal
NOAEL
is
50
mg/
kg
b.
w./
day
based
on
the
following:
reduced
body
weight
gains
and
reduced
feed
consumption
(
absolute
and
relative)
at
both
350
and
700
mg/
kg
b.
w./
day.
In
addition,
at
these
two
dose
levels,
a
doserelated
statistically
significant
increase
in
absolute
and
relative
(
to
body
weight)
liver
weights
occurred,
as
compared
to
controls.
Also,
increased
incidences
and/
or
severities
of
periportal
hepatocellular
hypertrophy
and
diffuse
and/
or
periportal
hepatocellular
vacuolation
were
observed
at
350
and
700
mg/
kg
b.
w./
day.
In
this
prenatal
toxicity
study
in
rabbits,
the
developmental
NOAEL
of
BAS
560
F
is
350
mg/
kg
b.
w./
day,
as
based
on
the
slight
but
statistically
significant
reduction
in
fetal
body
weights
at
700
mg/
kg
b.
w./
day.
Therefore,
because
developmental
toxicity
was
only
observed
at
dose
levels
that
were
maternally
toxic,
BAS
560
F
is
not
selectively
toxic
to
the
fetus.
In
addition,
BAS
560
F
was
not
teratogenic
in
rabbits.
5
Overall,
for
the
reproductive
and
developmental
toxicity
studies,
the
lowest
NOAEL
for
maternal/
parental
toxicity
was
39
mg/
kg
b.
w./
day
(
two­
generation
reproduction
study)
and
for
pup
toxicity
was
79
mg/
kg
b.
w./
day
(
two­
generation
reproduction
study).]

4.
Subchronic
toxicity.
[
The
subchronic
toxicity
of
BAS
560
F
was
investigated
in
a
dietary
28­
day
study
in
rats,
a
28­
day
oral
toxicity
study
in
dogs,
and
3­
month
toxicity
studies
in
rats,
mice,
and
dogs.
In
addition,
a
28­
day
neurotoxicity
study
was
conducted
with
rats.

The
signs
of
toxicity
observed
in
the
three
species
tested
were
overall
similar
and
consisted
of
reduced
body
weight
gain
at
the
highest
tested
dose
levels.
The
observed
effects
on
clinical
chemistry
in
rats
and
mice
can
be
linked
to
the
microscopic
effects
observed
in
the
liver.
The
effects
observed
typically
included
increased
cholesterol,
total
protein,
and
total
bilirubin
(
mice
only).
Organ
weights
and/
or
pathology
indicated
the
liver
to
be
the
only
consistent
target
organ
in
all
three
species
tested.
The
changes
included,
periportal
cytoplasmic
vacuolation
in
rats,
centrilobular
hepatocellular
hypertrophy
in
mice,
and
increased
liver
weights
in
rats,
mice,
and
dogs.

In
the
28­
day
neurotoxicity
study
with
rats,
there
was
no
evidence
of
neurotoxicity
in
all
treatment
groups,
with
an
No­
Observed­
Adverse­
Effect
Level
(
NOAEL)
for
neurotoxicity
of
15,000
in
the
diet
(
equivalent
to
1,371
mg/
kg
b.
w./
day
for
both
sexes
based
on
food
consumption
data).
These
results,
coupled
with
lack
of
neurotoxic
effects
observed
in
acute,
sub­
chronic
and
chronic
studies
with
other
species,
indicate
that
BAS
560
F
is
not
neurotoxic.]

5.
Chronic
toxicity.
[
The
chronic
toxicity
of
BAS
560
F
was
evaluated
in
a
1­
year
oral
administration
study
in
dogs,
a
24­
month
feeding
study
with
rats
and
an
18­
month
feeding
study
with
mice.

Administration
of
BAS
560
F
to
dogs
for
one
year
resulted
in
mild
increases
in
mean
alkaline
phosphatase
in
males
after
9
and
12
months
of
dosing
at
500
mg/
kg
b.
w./
day
(
highest
dose
tested).
Mean
absolute
and
relative
liver
weights
were
both
statistically
significantly
increased
in
females
at
500
mg/
kg
b.
w./
day
and
relative
liver
weights
were
statistically
significantly
increased
in
males
at
500
mg/
kg
b.
w./
day.
However,
there
were
no
associated
macroscopic
or
microscopic
findings
in
the
livers
of
these
animals.
Therefore,
the
slight
but
statistically
significant
differences
in
liver
weights
and
alkaline
phosphatase
(
in
males)
were
not
considered
to
be
of
toxicological
significance.
All
other
parameters
evaluated
including
mortality,
clinical
observations,
body
weights
and
food
consumption
data,
ophthalmology,
hematology,
coagulation
and
urinalysis
data,
and
macroscopic
and
microscopic
examinations
revealed
no
adverse
effects
due
to
administration
of
BAS
560
F.
Therefore,
the
NOAEL
for
oral
administration
of
BAS
560
F
to
pure­
bred
Beagle
Dogs
was
500
mg/
kg
b.
w./
day,
the
highest
dose
tested.
6
Treatment
of
Sprague­
Dawley
rats
with
BAS
560
F
for
24
months
resulted
in
markedly
reduced
body
weight
gains
in
females
at
5,000
(
26%)
and
20,000/
10,000
ppm
(
42%)
and
a
lesser
reduction
in
body
weight
gain
for
males
at
20,000
ppm
(
14%).
Microscopic
effects
in
the
liver
and
kidney
were
associated
with
clinical
chemistry
changes
in
males
and
females
at
doses
of
5,000
ppm
and
greater.
Slight
anemia
was
observed
in
females
at
5,000
ppm
and
higher,
which
was
reversed
at
24
months.
An
increase
in
the
incidence
of
hepatocellular
necrosis
after
12
months
and
benign
hepatocellular
adenomas
was
observed
in
females
at
5,000
ppm
and
greater
which
are
dietary
concentrations
that
exceeded
the
MTD.
Therefore,
the
NOAEL
for
systemic
toxicity
and
for
oncogenic
effects
following
dietary
administration
of
BAS
560
F
to
Sprague­
Dawley
rats
for
24
months,
was
500
ppm
(
25
mg/
kg
b.
w./
day
as
based
on
food
consumption
data).

Treatment
of
albino
mice
with
BAS
560
F
for
18
months
resulted
in
statistically
significant
increases
in
the
following:
liver
weights
(
absolute
and
relative,
in
females),
hepatocellular
hypertrophy
in
males,
renal
chronic
nephropathy
in
males
and
extramedullary
hematopoiesis
in
the
spleen
of
females
at
1,000
ppm,
the
next
highest
concentration
tested.
Therefore,
the
NOAEL
for
systemic
toxicity
following
dietary
administration
of
BAS
560
F
to
albino
mice
for
18
months,
was
250
ppm
(
46
mg/
kg
b.
w./
day
as
based
on
food
consumption
data).

A
statistically
significant
(
P<
0.01)
increase
in
the
incidence
of
hepatocellular
neoplasms
(
adenomas
and
carcinomas)
was
observed
in
the
livers
of
male
mice
receiving
7,000
ppm
(
19/
66,
28.8%),
as
compared
to
controls
(
6/
65,
9.2%).
There
was
also
a
marginal
increase
in
the
incidence
of
hepatocellular
neoplasms
in
females
receiving
7,000
ppm
(
4/
65),
as
compared
to
the
control
mice
(
2/
65).
The
incidence
of
14/
66
(
21.2%)
hepatocellular
adenoma
for
males
at
7,000
ppm
is
slightly
above
the
maximum
range
of
historical
control
data
at
the
testing
laboratory
(
14.8%)
and
at
Charles
River
Laboratories
(
19.2%).
The
incidence
of
5/
66
(
7.6%)
hepatocellular
carcinoma
in
males
at
7,000
ppm
is
within
the
maximum
range
of
historical
control
data
at
both
the
testing
facility
(
9.2%)
and
Charles
River
Laboratories
(
11.5%).
Although
the
number
of
hepatocellular
neoplasms
in
males
receiving
1,000
ppm
was
also
slightly
increased
(
9/
65,
13.8%)
compared
to
the
untreated
controls
(
6/
65,
9.2%),
this
slight
increase
was
not
statistically
significant
(
p<
0.05)
and
was
within
the
range
of
the
historical
controls
(
9.2­
18.5%)
at
the
testing
laboratory.
The
slight
increase
in
hepatocellular
neoplasms
in
male
mice
at
1,000
ppm
may
have
resulted
from
increased
survival
observed
at
termination
in
male
mice
at
1,000
ppm
as
compared
to
controls
(
55
versus
45
in
the
surviving
male
controls).
The
incidences
of
hepatocellular
neoplasms
in
terminally
sacrificed
male
mice
were
5/
45
or
11%,
3/
53
or
6%,
8/
55
or
15%
and
18/
54
or
33%,
at
respective
treatment
levels
of
0,
250,
1,000
and
7,000
ppm.

For
females,
whereas
the
incidence
of
hepatocellular
adenoma
was
the
same
(
2/
65
or
3.1%)
at
7,000
ppm
and
for
controls,
the
incidence
of
hepatocellular
carcinoma
was
slightly
increased
at
7,000
ppm
(
2/
65
or
3.1%)
versus
control
(
0/
65
or
0%).
Since
this
incidence
of
hepatocellular
carcinoma
(
3.1%)
for
females
at
7,000
ppm
is
slightly
above
the
maximum
range
of
historical
control
data
at
both
the
testing
facility
(
1.5%)
and
Charles
River
Laboratories
(
2.0%),
the
incidence
represents
an
equivocal
finding.
However,
because
this
increase
was
very
small,
was
7
not
statistically
significant,
and
did
not
demonstrate
decreased
latency
compared
to
the
controls,
this
finding
was
considered
to
represent
only
equivocal
toxicologic
significance.

Therefore,
based
on
the
weight­
of­
the­
evidence
analysis,
the
NOAEL
for
oncogenicity
is
1,000
ppm
(
approximately
190
mg/
kg
of
b.
w./
day,
calculated
from
food
consumption
data
and
nominal
concentrations)
based
on
the
increased
incidence
of
hepatocellular
neoplasms
observed
in
male
mice
at
7,000
ppm,
as
compared
to
controls.

In
summary,
long­
term
exposure
studies
with
BAS
560
F
in
dogs,
rats
and
mice
resulted
in
increased
liver
weights
with
corresponding
changes
in
clinico­
chemical
parameters.
Microscopic
pathological
changes
were
identified
in
the
liver,
kidney,
and
spleen
for
rats
and/
or
mice.
The
main
target
organ
was
identified
as
the
liver
in
all
species.
Additionally,
increased
incidences
of
primary
hepatocellular
neoplasms
were
observed
at
the
highest
doses
in
rats
and
mice.]

6.
Animal
metabolism.
[
BAS
560
F
was
rapidly
absorbed
and
efficiently
excreted
following
oral
administration
in
the
rat.
The
amount
of
absorption
ranged
from
approximately
89
to
92%
of
the
administered
dose
of
10
mg/
kg
b.
w.
Most
of
the
administered
dose
was
eliminated
via
bile
within
72
hours
(
85.2
to
90.1%)
and
feces
within
7
days
(
84.1
to
98.8%),
with
a
small
amount
(
0.69
to
6.6%)
in
urine.
BAS
560
F­
related
residues
showed
no
potential
for
accumulation
as
<
1.2%
of
the
applied
dose
was
retained
over
seven
days,
with
highest
levels
of
residues
found
in
the
liver,
GI
tract,
plasma,
blood,
kidney,
and
fat.
The
tissue
retention
of
the
orally
administered
dose
was
less
than
2%
at
48­
72
hours
and
less
than
1.2%
at
168
hours.
BAS
560
F
was
extensively
metabolized
in
the
rat
to
multiple
metabolites
formed
via
demethylation
of
the
aromatic
methoxy­
group(
s)
followed
by
mono­
O­
glycosidation,
hydroxylation
of
the
bromophenyl
ring,
and
hydroxylation
of
the
methyl
substituent
to
hydroxymethyl
followed
by
O­
glycosidation
or
further
oxidation
to
aldehyde
or
lactone.]

7.
Metabolite
toxicology.
[
In
plant
metabolism
studies
conducted
in
grapevines
with
BAS
560
F,
the
parent
compound
was
the
principal
residue
in
grapes.
BAS
560
F
is
metabolized
through
methyl
and
ring
oxidative
biotransformations,
followed
by
enzymatic
glucoside
conjugation
reactions
to
yield
the
conjugates
from
their
corresponding
aglycons.
All
major
metabolites,
which
were
present
at
very
low
levels,
are
considered
non­
relevant
as
all
were
detected
in
the
rat
metabolism
study
as
aglycons
or
conjugates,
and
can
therefore
be
considered
as
not
toxicologically
significant.
Thus,
only
parent
BAS
560
F
is
considered
relevant
to
define
the
residue
in
plants.

The
results
from
a
hydrolysis
study
designed
to
simulate
different
industrial
and
household
processes
(
pasteurization,
brewing,
boiling
and
sterilization)
showed
that
BAS
560
F
is
stable.
Therefore,
BAS
560
F
as
unchanged
parent
is
proposed
as
the
relevant
residue
in
grapes
and
industrial
or
household
preparations
of
grapes.
8
Since
BAS
560
F
is
not
registered
for
use
in
the
United
States,
the
toxicity
of
metabolites
formed
in
matrices
other
than
the
raw
or
processed
treated
commodity
(
e.
g.,
water,
soil)
is
not
relevant.]

8.
Endocrine
disruption.
[
Data
from
the
reproduction
/
developmental
toxicity
and
short­
and
long­
term
repeated
dose
toxicity
studies
with
BAS
560
F
in
the
rat,
rabbit,
mouse,
or
dog,
do
not
suggest
any
endocrine
disruption
activity.
This
information
is
based
on
the
absence
of
any
treatment­
related
effects
from
the
histopathological
examination
of
endocrine
organs
as
well
as
the
low
level
of
concern
for
possible
effects
on
fertility,
reproductive
performance,
or
any
other
aspect
of
reproductive
function,
or
on
growth
and
development
of
the
offspring.]

C.
Aggregate
Exposure
1.
Dietary
exposure.
[
Assessments
were
conducted
to
evaluate
the
potential
risk
due
to
chronic
and
acute
dietary
exposure
of
the
U.
S.
population
to
residues
of
BAS
560
F.
This
fungicide
is
not
registered
for
use
in
the
United
States
and
therefore
exposure
to
BAS
560
F
residues
is
limited
to
consumption
of
imported
food
commodities.
This
analysis
was
conducted
to
support
the
BAS
560
F
U.
S.
import
tolerance
for
grapes
and
wine.]

i.
Food.
[
The
dietary
assessment
analysis
followed
an
initial
tier
approach.
Default
processing
factors,
100%
crop
treated,
and
proposed
tolerance
values
were
assumed
in
the
assessment.
Dietary
exposure
assessments
were
conducted
using
both
Exponent's
Dietary
Exposure
Evaluation
Module
(
DEEM­
FCID)
and
Infoscientific's
Cumulative
and
Aggregate
Risk
Evaluation
System
(
CARES,
version
1.1)
software.
Results
of
the
chronic
exposure
estimates
were
compared
against
the
chronic
Population
Adjusted
Dose
(
cPAD)
of
0.25
mg/
kg
b.
w./
day
that
was
based
on
the
NOAEL
from
the
rat
chronic
toxicity
study,
a
safety
factor
of
100,
and
no
additional
FQPA
safety
factor.
The
acute
dietary
exposure
estimates
are
reported
but
were
not
compared
to
aPAD
values
since
BAS
560
F
is
not
acutely
toxic
and
therefore
aRfD
and
aPAD
values
were
not
warranted
(
see
toxicology
results).

Results
of
the
chronic
dietary
exposure
assessments
are
listed
in
Table
1.
The
estimated
chronic
dietary
exposure
from
imported
grapes
was
less
than
1%
of
the
cPAD
for
all
subpopulations.
9
Table
1.
Chronic
Dietary
Exposure
Assessment
for
BAS
560
F
Population
Exposure
Estimate
%
cRfD
%
cPAD
Subgroups
(
mg/
kg
b.
w./
day)

U.
S.
population
0.000268
0.11
0.11
Birth
to
1
year
0.000523
0.21
0.21
1­
2
years
0.001881
0.75
0.75
3­
5
years
0.001138
0.46
0.46
1­
6
years
0.001289
0.52
0.52
6­
12
years
0.000427
0.17
0.17
13­
19
years
0.00015
0.06
0.06
Females
13­
49
years
0.000132
0.05
0.05
Males
20­
49
years
0.000121
0.05
0.05
Adults
50+
years
0.000138
0.06
0.06
Calculated
using
DEEM­
FCID
software
Assessment
conducted
with
import
tolerance
values,
100%
CT,
and
default
process
values
%
cPAD
=
percent
of
chronic
population
adjusted
dose
Exposure
estimates
for
BAS
560
F
acute
dietary
assessment
ranged
from
0.00182
to
0.06725
mg/
kg
b.
w./
day
for
all
subpopulations
at
the
99.9th
percentile
(
Tables
A­
2
and
A­
3).
The
acute
reference
dose
and
PAD
were
not
calculated
for
the
acute
dietary
assessment
since
toxicology
studies
have
shown
that
BAS
560
F
poses
no
acute
dietary
risk.
Therefore
no
%
aPAD
has
been
established.

Table
A­
2.
Acute
Dietary
Exposure
Assessment
for
BAS
560
F
Conducted
using
DEEM­
FCID
Software
Population
95th
percentile
99.9th
percentile
%
aRf
D
%
aPAD
Exposure
Estimate
Exposure
Estimate
Subgroups
(
mg/
kg
b.
w./
day)
(
mg/
kg
b.
w./
day)

U.
S.
population
0.00118
0.01646
NA
NA
Birth
to
1
year
0.00307
0.03087
NA
NA
1­
2
years
0.00995
0.06725
NA
NA
3­
5
years
0.00625
0.03076
NA
NA
1­
6
years
0.00721
0.03873
NA
NA
6­
12
years
0.00223
0.01643
NA
NA
13­
19
years
0.00076
0.00831
NA
NA
Females
13­
49
years
0.00067
0.00565
NA
NA
Males
20­
49
years
0.00056
0.00492
NA
NA
Adults
50+
years
0.00069
0.00438
NA
NA
Assessment
conducted
with
import
tolerance
values,
100%
CT,
and
default
process
values
%
aPAD
=
percent
of
chronic
population
adjusted
dose
10
NA
=
not
applicable
Table
A­
3.
Acute
Dietary
Exposure
Assessment
for
BAS
560
F
Conducted
using
CARES
Software
Population
Exposure
Estimate
%
aPAD
Subgroups
(
mg/
kg
b.
w./
day)
Birth
to
1
year
0.02475
NA
1­
2
years
0.02238
NA
3­
5
years
0.01328
NA
1­
6
years
0.01678
NA
6­
12
years
0.00695
NA
13­
19
years
0.00235
NA
Females
13­
49
years
0.00278
NA
Males
20­
49
years
0.00182
NA
Adults
50+
years
0.00239
NA
Exposure
estimates
represent
the
99.9th
percentile
Assessment
conducted
with
import
tolerance
values,
100%
CT,
and
default
process
values
%
aPAD
=
percent
of
chronic
population
adjusted
dose
NA
=
not
applicable
ii.
Drinking
water.
[
The
only
potential
exposure
of
BAS
560
F
to
the
U.
S.
population
is
through
the
consumption
of
imported
wine
or
grapes
from
the
European
Union.
BAS
560
F
products
are
not
labeled
for
any
uses
in
the
U.
S.
Therefore,
this
eliminates
the
potential
for
contamination
of
U.
S.
drinking
water
supplies.
The
potential
for
drinking
water
exposure
to
the
U.
S.
general
population
is
considered
to
be
insignificant.]

2.
Non­
dietary
exposure.
[
The
only
potential
exposure
of
BAS
560
F
to
the
U.
S.
population
is
through
the
consumption
of
imported
wine
or
grapes
from
the
European
Union.
BAS
560
F
products
are
not
labeled
for
any
uses
in
the
U.
S.
Therefore,
this
eliminates
the
potential
for
occupational
or
residential
exposure.
The
potential
for
nondietary
exposure
to
the
U.
S.
general
population
is
considered
to
be
insignificant.]

D.
Cumulative
Effects
[
At
this
time,
there
is
no
available
information
to
indicate
that
BAS
560
F
or
its
metabolites
have
a
common
mechanism
of
toxicity
with
other
substances.
Therefore,
there
is
no
reason
to
include
this
pesticide
or
its
metabolites
in
a
cumulative
risk
assessment.
For
the
purposes
of
this
tolerance
action
EPA
has
not
assumed
that
BAS
560
F
and
its
metabolites
have
a
common
mechanism
of
toxicity
with
other
substances.]

E.
Safety
Determination
11
1.
U.
S.
population.
[
Results
of
the
dietary
exposure
analysis
demonstrate
with
reasonable
certainty
that
no
harm
to
the
general
U.
S.
population
or
any
subpopulation
would
results
from
the
acceptance
of
the
proposed
BAS
560
F
U.
S.
import
tolerances
for
table
and
wine
grapes.
Exposure
estimates
remained
well
below
the
U.
S.
EPA's
level
of
concern
(
100%
of
PAD)
with
%
cPAD
values
not
exceeding
1%
for
all
subpopulations.]

2.
Infants
and
children.
[
Results
of
the
dietary
exposure
analysis
demonstrate
with
with
reasonable
certainty
that
no
harm
to
the
general
U.
S.
population
or
any
subpopulation,
including
infants
and
children,
would
results
from
the
acceptance
of
the
proposed
BAS
560
F
U.
S.
import
tolerances
for
table
and
wine
grapes.
Exposure
estimates
remained
well
below
the
U.
S.
EPA's
level
of
concern
(
100%
of
PAD)
with
%
cPAD
values
not
exceeding
1%
for
all
subpopulations,
including
infants
and
children.]

F.
International
Tolerances
[
No
maximum
residue
levels
(
MRLs)
have
been
established
for
BAS
560
F
by
the
Codex
Alimentarius
Commission
(
CODEX)
or
in
Canada
or
Mexico.]