Document ID: EPA-HQ-OPP-2006-0670-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-08-25T04:00Z

Page
1
COMPANY
FEDERAL
REGISTER
DOCUMENT
SUBMISSION
TEMPLATE
(
7/
1/
2006)

EPA
Registration
Division
contact:
[
Joanne
I.
Miller
 
PM/
23
 
703­
305­
6224]

INSTRUCTIONS:
Please
utilize
this
outline
in
preparing
tolerance
petition
documents.
In
cases
where
the
outline
element
does
not
apply
please
insert
"
NARemove
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.]

TEMPLATE:

[
Dow
AgroSciences
LLC]

[
PP
7F4851]

EPA
has
received
a
pesticide
petition
([
PP
7F4851])
from
[
Dow
AgroSciences
LLC
formerly
known
as
DowElanco],
[
9330
Zionsville
Road
 
Indianapolis,
IN
46268­
1054]
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
2.
to
establish
an
exemption
from
the
requirement
of
a
tolerance
for
[
Flumetsulam]
in
or
on
the
raw
agricultural
commodity
[
dry
beans]
at
[
0.05]
parts
per
million
(
ppm).
The
proposed
analytical
method
involves
homogenization,
filtration,
partition
and
cleanup
with
analysis
by
high
performance
liquid
chromatography
using
UV
detection.
EPA
has
determined
that
the
petition
contains
data
or
information
regarding
the
elements
set
forth
in
section
408
(
d)(
2)
of
the
FDDCA;
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
Page
2
1.
Plant
metabolism
2.
Analytical
method.
[
There
is
a
practical
analytical
method
for
detecting
and
measuring
levels
of
Flumetsulam
in
or
on
food
with
a
limit
of
quantitation
(
LOQ)
of
0.010
ppm,
and
a
limit
of
detection
of
0.005
ppm
that
allows
monitoring
of
food
with
residues
at
or
above
the
levels
set
in
these
tolerances.
EPA
has
provided
information
on
this
method
to
FDA.
The
method
is
available
to
anyone
who
is
interested
in
pesticide
residue
enforcement.]

3.
Magnitude
of
residues.
[
No
detectable
residues
of
Flumetsulam
were
found
in
any
of
the
dry
bean
samples
obtained
from
multiple
sites
and
multiple
varieties
and
analyzed
using
a
method
with
a
limit
of
detection
of
0.005
ppm.]

B.
Toxicological
Profile
1.
Acute
toxicity.
[
Flumetsulam
has
low
acute
toxicity.
The
rat
oral
LD
INF
50/
INF
is
1.2
mg/
L
air
(
the
highest
attainable
concentration).
In
addition,
Flumetsulam
is
not
a
skin
sensitizer
in
guinea
pigs,
is
not
a
dermal
irritant
and
is
not
an
ocular
irritant.
Therefore
based
on
the
available
acute
toxicity
data,
Flumetsulam
does
not
pose
any
acute
dietary
risks.]

2.
Genotoxicity.
[
Flumetsulam
is
not
genotoxic.
The
following
studies
have
been
conducted
and
all
were
negative
for
genotoxic
responses:
a
dominant
lethal
assay,
an
In
vivo
rat
cytogenic
study,
an
In
vitro
Salmonella
and
Saccharomyces
assay,
and
In
vivo
mouse
host­
mediated
assay,
and
an
unscheduled
DNA
synthesis
assay
in
rats.]

3.
Reproductive
and
developmental
toxicity.
[
In
a
2­
generation
reproduction
study
in
rats,
there
was
no
compound­
related
reproductive
toxicity.
The
No­
Observed­
Effect
Level
(
NOEL)
was
greater
than
1,000
mg/
kg/
day.
Developmental
toxicity
was
studied
using
rats
and
rabbits.
The
developmental
study
in
rats
resulted
in
a
developmental
NOEL
greater
than
1.000
mg/
kg/
day
(
highest
dose
tested)
and
a
maternal
NOEL
of
500
mg/
kg/
day.
A
study
in
rabbits
resulted
in
a
developmental
NOEL
equal
to
or
greater
than
700
mg/
kg/
day
(
highest
dose
tested)
with
a
maternal
NOEL
of
100
mg/
kg/
day,
and
maternal
LOEL
(
lowest
observed
effect
level)
of
500
mg/
kg/
day
evidenced
by
decreased
body
weight
gain.
Based
on
all
of
the
data
for
Flumetsulam,
there
is
no
evidence
of
developmental
toxicity
at
dose
levels
that
do
not
result
in
maternal
toxicity.]

4.
Subchronic
toxicity.
[
In
a
13­
week
oral
feeding
study
in
mice
at
5,000
mg/
kg/
day,
slight
effects
on
the
liver,
kidney,
and
cecum
appeared
to
represent
adaptive
responses
to
treatment
and
have
questionable
toxicological
significance.
The
NOEL
was
1,000
mg/
kg/
day
(
limit
dose).
In
a
13­
week
oral
feeding
study
in
dogs,
the
lowest­
observed­
effect
level
(
LOEL)
for
both
male
and
female
dogs
was
500
mg/
kg/
day.
A
NOEL
was
not
established
for
males
or
females.
In
a
13­
week
Page
3
dietary
study
in
rats,
the
NOEL
was
250
mg/
kg/
day,
and
the
LOEL
was
1,000
mg/
kg/
day.]

5.
Chronic
toxicity.
[
In
a
1­
year
dietary
study
in
dogs,
the
NOEL
was
100
mg/
kg/
day,
and
the
LOEL
was
500
mg/
kg/
day.
The
animals
were
administered
feed
containing
0,
20,
100,
and
500
mg/
kg/
day.
Reduced
body
weights
and
inflammatory
and
atrophic
changes
in
the
kidneys
occurred
in
the
500
mg/
kg/
day
dose
groups.
In
a
combined
feeding
carcinogenicity/
chronic
study
in
mice,
there
were
no
treatment
related
effects,
and
there
was
no
evidence
of
a
carcinogenic
response.
Systemic
NOEL
was
greater
than
or
equal
to
1,000
mg/
kg/
day
(
limit
dose);
a
LOEL
was
not
established.
In
a
combined
feeding
carcinogenicity/
chronic
study
in
rats,
renal
pathological
alterations
were
seen
in
males.
No
treatment
related
effects
were
seen
in
females
at
the
highest
dose
(
1,000
mg/
kg/
day)
which
is
the
limit
dose.
There
was
no
carcinogenic
response.
The
NOELs
were
500
mg/
kg/
day
in
males
and
1,000
mg/
kg/
day
in
females.
The
LOEL
was
1,000
mg/
kg/
day
in
males;
a
LOEL
was
not
established
in
females.
Based
on
the
chronic
toxicity
data,
EPA
has
established
the
RfD
for
Flumetsulam
at
1.0
milligram
(
mg)/
kilogram
(
kg)/
day.
The
RfD
for
Flumetsulam
is
based
on
the
1
year
chronic
study
in
dogs
with
a
NOEL
of
100
mg/
kg/
day,
and
an
uncertainty
(
or
safety)
factor
of
100.
Thus,
it
would
not
be
necessary
to
require
the
application
of
an
additional
uncertainty
factor
above
the
100­
fold
factor
already
applied
to
the
NOEL.]

6.
Animal
metabolism.
[
Disposition
and
metabolism
of
Flumetsulam
were
tested
in
male
and
female
rats
and
male
mice
at
an
oral
dose
of
5
and
1,000
mg/
kg
for
rats
and
1,000
mg/
kg
for
mice.
Flumetsulam
was
rapidly
excreted.
The
majority
of
a
radioactive
dose
was
excreted
in
48
hours
of
all
dose
groups.
The
principle
route
for
elimination
was
the
urine,
and
to
a
lesser
extent
by
fecal
elimination.
Detectable
levels
of
residual
radioactivity
were
observed
in
the
carcass
and
stomach
at
72
hours
post­
dose.
HPLC
and
TLC
analysis
of
urine
and
fecal
extracts
showed
no
apparent
metabolism
of
Flumetsulam.]

7.
Metabolite
toxicology.
[
There
are
no
Flumetsulam
metabolites
of
toxicological
significance.]

8.
Endocrine
disruption.
[
There
is
no
evidence
to
suggest
that
Flumetsulam
has
an
effect
on
any
endocrine
system.]

C.
Aggregate
Exposure
1.
Dietary
exposure.
[
For
purposes
of
assessing
the
potential
dietary
exposure
under
these
tolerances,
exposure
is
estimated
based
on
the
Theoretical
Maximum
Residue
Contribution
(
TMRC)
from
the
existing
and
pending
tolerances
for
Flumetsulam
on
food
crops.]

i.
Food.
[
The
TMRC
is
obtained
by
multiplying
the
tolerance
level
residues
by
the
consumption
data
which
estimates
the
amount
of
those
food
products
eaten
Page
4
by
various
population
subgroups.
Exposure
of
humans
to
residues
could
also
result
if
such
residues
are
transferred
to
meat,
milk,
poultry
or
eggs.
The
following
assumptions
were
used
in
conducting
this
exposure
assessment:
100%
of
the
crops
were
treated,
the
RAC
residues
would
be
at
the
level
of
the
tolerance,
certain
processed
food
residues
would
be
at
anticipated
(
average)
levels
based
on
processing
studies,
and
all
current
and
pending
tolerances
were
included.
This
results
in
an
overestimate
of
human
exposure
and
a
conservative
assessment
of
risk.
Based
on
a
NOEL
of
100
mg/
kg/
day
in
a
1
year
chronic
feeding
study
in
the
dog
and
a
hundredfold
safety
factor,
the
reference
dose
(
RfK)
would
be
1.0
mg/
kg/
day.
The
TMRC
for
the
general
population
would
be
4.1
X
10­<
SUP>­
5</
SUP>
mg/
kg/
day
or
0.0041%
of
the
RfD.
For
non­
nursing
infants,
the
TMRC
would
be
1.37
X
10<
SUP>­
5/
SUP>
mg/
kg/
day
or
0.014%
of
the
RfD.]

ii.
Drinking
Water.
[
Another
potential
source
of
dietary
exposure
to
residues
of
pesticides
is
residues
in
drinking
water.
There
is
no
established
Maximum
Concentration
Level
for
residues
of
Flumetsulam
in
drinking
water.
Although
there
have
been
limited
detections
at
ppb
levels
in
some
of
the
specially
designed
studies
under
highly
vulnerable
test
conditions,
and
at
elevated
non­
labeled
application
rates,
no
ongoing
monitoring
studies
have
reported
residues
of
Flumetsulam
in
ground
or
surface
waters.

Based
on
the
physical
and
chemical
characteristics
of
Flumetsulam
such
as
water
solubility
and
its
stability
under
hydrolysis
and
photolysis,
it
has
potential
for
downward
movement
through
the
soil
profile.
Degradation
based
on
over
20
laboratory
studies
indicated
a
half­
life
range
of
2
weeks
to
4
months
with
80%
less
than
2
months.
Degradation
is
driven
primarily
by
microbial
processes.
However
based
on
the
low
application
rate
and
detection
in
groundwater
samples,
and
only
under
extremely
vulnerable
soil
conditions
at
elevated
non­
labeled
application
rates
with
detections
in
single
digit
ppb
levels,
Flumetsulam
is
not
anticipated
to
be
a
groundwater
contaminant.

In
summary,
these
data
on
potential
water
exposure
indicate
insignificant
additional
dietary
intake
of
Flumetsulam,
and
any
exposure
is
more
than
compensated
for
in
the
conservative
dietary
risk
evaluation.
Therefore,
it
is
concluded
that
there
is
a
reasonable
certainty
of
no
harm
even
at
potential
upper
limit
exposures
to
Flumetsulam
from
drinking
water.]

2.
Non­
dietary
exposure.
[
There
are
no
non­
dietary
uses
for
Flumetsulam
registered
under
the
Federal
Insecticide,
Fungicide
and
Rodenticide
Act.
Potential
exposures
for
children
are,
therefore,
limited
to
dietary
exposure.]

D.
Cumulative
Effects
[
The
potential
for
cumulative
effects
of
Flumetsulam
and
other
substances
that
have
a
common
mechanism
of
toxicity
was
considered.
The
mammalian
toxicity
of
Flumetsulam
is
well
defined.
However,
no
reliable
information
exists
to
Page
5
indicate
that
toxic
effects
produced
by
Flumetsulam
would
be
cumulative
with
those
of
any
other
chemical
compound.
Additionally,
Flumetsulam
does
not
appear
t
produce
a
toxic
metabolite
produced
by
other
substances.
Therefore,
consideration
of
a
common
mechanism
of
toxicity
with
other
compounds
is
not
appropriate
at
this
time.
Thus,
only
the
potential
exposures
to
Flumetsulam
were
considered
in
the
aggregate
exposure
assessment.]

E.
Safety
Determination
1.
U.
S.
population.
[
Based
on
a
NOEL
of
100
mg/
kg/
bwt/
day
from
a
one
year
dog
feeding
study
with
a
reduced
weight
and
inflammatory
and
atrophic
kidney
effect,
and
using
an
uncertainty
factor
of
100
to
account
for
the
interspecies
extrapolation
and
intraspecies
variability,
a
Reference
Dose
(
RfD)
of
1.0
mg/
kg/
bwt/
day
was
used
for
this
assessment
of
chronic
risk.
As
indicated,
there
is
no
endpoint
of
concern
identified
with
acute
and
short
or
intermediate
term
exposures.
The
existing
and
proposed
tolerances
would
utilize
0.000041
mg/
kg/
bwt/
day,
or
less
than
0.01%
of
the
RfD
for
the
U.
S.
population.
And,
as
indicated
previously,
whatever
upper
limit
might
be
used
for
drinking
water
exposure,
the
exposure
estimate
for
Flumetsulam
would
not
exceed
the
RfD.
Generally,
exposures
below
100
percent
of
the
RfD
are
of
no
concern
because
the
RfD
represents
the
level
at
or
below
which
daily
aggregate
dietary
exposure
over
a
lifetime
will
not
pose
appreciable
risk
to
human
health.
Thus,
there
is
a
reasonable
certainty
that
no
harm
will
result
from
aggregate
exposure
to
Flumetsulam
residues.]

2.
Infants
and
children.
[
In
assessing
the
potential
for
additional
sensitivity
of
infants
and
children
to
residues
of
Flumetsulam,
data
from
developmental
toxicity
studies
in
the
rat
and
rabbit,
and
a
2
generation
reproduction
study
in
the
rat
were
considered.
The
developmental
toxicity
studies
are
designed
to
evaluate
adverse
effects
on
the
developing
organism
during
prenatal
development
resulting
from
pesticide
exposure
to
one
or
both
parents.
Reproduction
studies
provide
pesticide
exposure
to
one
or
both
parents.
Reproduction
studies
provide
(
1)
information
relating
to
effects
from
exposure
to
the
pesticide
on
the
reproductive
capability
of
mating
animals
and
(
2)
data
on
systemic
toxicity.

As
indicated
previously,
reproductive
and
developmental
toxicity
was
studied
using
rats
and
rabbits.
The
data
base
is
complete,
and
based
on
all
of
the
data
for
Flumetsulam;
there
is
no
evidence
of
reproductive
or
developmental
toxicity
at
dose
levels
that
do
not
result
in
maternal
toxicity.

FFDCA
section
408
provides
that
EPA
may
apply
an
additional
safety
factor
for
infants
and
children
in
the
case
of
threshold
effects
to
account
for
pre­
and
postnatal
effects
for
children
is
complete.
These
data
suggest
minimal
concern
for
developmental
or
reproductive
toxicity,
and
do
not
indicate
any
increased
pre­
or
post­
natal
sensitivity.
Therefore,
an
additional
uncertainty
factor
is
not
necessary
to
Page
6
protect
the
safety
of
infants
and
children,
and
that
the
RfD
at
1.0
mg/
kg/
day
is
appropriate
for
assessing
aggregate
risk
to
infants
and
children.

The
percent
of
the
RfD
that
will
be
utilized
by
the
aggregate
exposure
from
all
tolerances
to
Flumetsulam
will
be
less
than
0.1%
for
non­
nursing
infants
and
for
children
(
1­
6
years
of
age).
Therefore,
based
on
the
completeness
and
reliability
of
the
toxicity
data
and
the
conservative
exposure
assessment,
it
is
concluded
that
there
is
a
reasonable
certainty
that
no
harm
will
result
to
infants
and
children
from
aggregate
exposure
to
Flumetsulam
residues.]

F.
International
Tolerances
[
There
are
no
Codex
Maximum
Residue
Levels
established
for
Flumetsulam
(
Joanne
Miller).]