Document ID: EPA-HQ-OPP-2003-0211-0001
Agency: epa
Document Type: Notice
Title: Dinotefuran; Notice of Filing a Pesticide Petition to Establish a Tolerance for a Certain Pesticide Chemical in or on Food
Posted Date: 2003-07-02T04:00Z

39547
Federal
Register
/
Vol.
68,
No.
127
/
Wednesday,
July
2,
2003
/
Notices
F.
International
Tolerances
To
date,
no
international
tolerances
exist
for
indoxacarb.
[
FR
Doc.
03
 
16739
Filed
7
 
1
 
03;
8:
45
am]

BILLING
CODE
6560
 
50
 
S
ENVIRONMENTAL
PROTECTION
AGENCY
[
OPP
 
2003
 
0211;
FRL
 
7312
 
8]

Dinotefuran;
Notice
of
Filing
a
Pesticide
Petition
to
Establish
a
Tolerance
for
a
Certain
Pesticide
Chemical
in
or
on
Food
AGENCY:
Environmental
Protection
Agency
(
EPA).
ACTION:
Notice.

SUMMARY:
This
notice
announces
the
initial
filing
of
a
pesticide
petition
proposing
the
establishment
of
regulations
for
residues
of
a
certain
pesticide
chemical
in
or
on
various
food
commodities.
DATES:
Comments,
identified
by
docket
ID
number
OPP
 
2003
 
0211,
must
be
received
on
or
before
August
1,
2003.
ADDRESSES:
Comments
may
be
submitted
electronically,
by
mail,
or
through
hand
delivery/
courier.
Follow
the
detailed
instructions
as
provided
in
Unit
I.
of
the
SUPPLEMENTARY
INFORMATION.

FOR
FURTHER
INFORMATION
CONTACT:
Rita
Kumar,
Registration
Division
(
7505C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460
 
0001;
telephone
number:
(
703)
308
 
8291;
e­
mail
address:
kumar.
rita@
epa.
gov.

SUPPLEMENTARY
INFORMATION:

I.
General
Information
A.
Does
this
Action
Apply
to
Me?

You
may
be
potentially
affected
by
this
action
if
you
are
an
agricultural
producer,
food
manufacturer,
or
pesticide
manufacturer.
Potentially
affected
entities
may
include,
but
are
not
limited
to:
 
Crop
production
(
NAICS
111)
 
Animal
production
(
NAICS
112)
 
Food
manufacturing
(
NAICS
311)
 
Pesticide
manufacturing
(
NAICS
32532)
This
listing
is
not
intended
to
be
exhaustive,
but
rather
provides
a
guide
for
readers
regarding
entities
likely
to
be
affected
by
this
action.
Other
types
of
entities
not
listed
in
this
unit
could
also
be
affected.
The
North
American
Industrial
Classification
System
(
NAICS)
codes
have
been
provided
to
assist
you
and
others
in
determining
whether
this
action
might
apply
to
certain
entities.
If
you
have
any
questions
regarding
the
applicability
of
this
action
to
a
particular
entity,
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.

B.
How
Can
I
Get
Copies
of
This
Document
and
Other
Related
Information?
1.
Docket.
EPA
has
established
an
official
public
docket
for
this
action
under
docket
identification
(
ID)
number
OPP
 
2003
 
0211.
The
official
public
docket
consists
of
the
documents
specifically
referenced
in
this
action,
any
public
comments
received,
and
other
information
related
to
this
action.
Although
a
part
of
the
official
docket,
the
public
docket
does
not
include
Confidential
Business
Information
(
CBI)
or
other
information
whose
disclosure
is
restricted
by
statute.
The
official
public
docket
is
the
collection
of
materials
that
is
available
for
public
viewing
at
the
Public
Information
and
Records
Integrity
Branch
(
PIRIB),
Rm.
119,
Crystal
Mall
#
2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA.
This
docket
facility
is
open
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
docket
telephone
number
is
(
703)
305
 
5805.
2.
Electronic
access.
You
may
access
this
Federal
Register
document
electronically
through
the
EPA
Internet
under
the
``
Federal
Register''
listings
at
http://
www.
epa.
gov/
fedrgstr/.
An
electronic
version
of
the
public
docket
is
available
through
EPA's
electronic
public
docket
and
comment
system,
EPA
Dockets.
You
may
use
EPA
Dockets
at
http://
www.
epa.
gov/
edocket/
to
submit
or
view
public
comments,
access
the
index
listing
of
the
contents
of
the
official
public
docket,
and
to
access
those
documents
in
the
public
docket
that
are
available
electronically.
Although
not
all
docket
materials
may
be
available
electronically,
you
may
still
access
any
of
the
publicly
available
docket
materials
through
the
docket
facility
identified
in
Unit
I.
B.
1.
Once
in
the
system,
select
``
search,''
then
key
in
the
appropriate
docket
ID
number.
Certain
types
of
information
will
not
be
placed
in
EPA's
Dockets.
Information
claimed
as
CBI
and
other
information
whose
disclosure
is
restricted
by
statute,
which
is
not
included
in
the
official
public
docket,
will
not
be
available
for
public
viewing
in
EPA's
electronic
public
docket.
EPA's
policy
is
that
copyrighted
material
will
not
be
placed
in
EPA's
electronic
public
docket
but
will
be
available
only
in
printed,
paper
form
in
the
official
public
docket.
To
the
extent
feasible,
publicly
available
docket
materials
will
be
made
available
in
EPA's
electronic
public
docket.
When
a
document
is
selected
from
the
index
list
in
EPA
Dockets,
the
system
will
identify
whether
the
document
is
available
for
viewing
in
EPA's
electronic
public
docket.
Although
not
all
docket
materials
may
be
available
electronically,
you
may
still
access
any
of
the
publicly
available
docket
materials
through
the
docket
facility
identified
in
Unit
I.
B.
EPA
intends
to
work
towards
providing
electronic
access
to
all
of
the
publicly
available
docket
materials
through
EPA's
electronic
public
docket.
For
public
commenters,
it
is
important
to
note
that
EPA's
policy
is
that
public
comments,
whether
submitted
electronically
or
in
paper,
will
be
made
available
for
public
viewing
in
EPA's
electronic
public
docket
as
EPA
receives
them
and
without
change,
unless
the
comment
contains
copyrighted
material,
CBI,
or
other
information
whose
disclosure
is
restricted
by
statute.
When
EPA
identifies
a
comment
containing
copyrighted
material,
EPA
will
provide
a
reference
to
that
material
in
the
version
of
the
comment
that
is
placed
in
EPA's
electronic
public
docket.
The
entire
printed
comment,
including
the
copyrighted
material,
will
be
available
in
the
public
docket.
Public
comments
submitted
on
computer
disks
that
are
mailed
or
delivered
to
the
docket
will
be
transferred
to
EPA's
electronic
public
docket.
Public
comments
that
are
mailed
or
delivered
to
the
docket
will
be
scanned
and
placed
in
EPA's
electronic
public
docket.
Where
practical,
physical
objects
will
be
photographed,
and
the
photograph
will
be
placed
in
EPA's
electronic
public
docket
along
with
a
brief
description
written
by
the
docket
staff.

C.
How
and
to
Whom
Do
I
Submit
Comments?
You
may
submit
comments
electronically,
by
mail,
or
through
hand
delivery/
courier.
To
ensure
proper
receipt
by
EPA,
identify
the
appropriate
docket
ID
number
in
the
subject
line
on
the
first
page
of
your
comment.
Please
ensure
that
your
comments
are
submitted
within
the
specified
comment
period.
Comments
received
after
the
close
of
the
comment
period
will
be
marked
``
late.''
EPA
is
not
required
to
consider
these
late
comments.
If
you
wish
to
submit
CBI
or
information
that
is
otherwise
protected
by
statute,
please
follow
the
instructions
in
Unit
I.
D.
Do
not
use
EPA
Dockets
or
e­
mail
to
submit
CBI
or
information
protected
by
statute.
1.
Electronically.
If
you
submit
an
electronic
comment
as
prescribed
in
this
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/
Vol.
68,
No.
127
/
Wednesday,
July
2,
2003
/
Notices
unit,
EPA
recommends
that
you
include
your
name,
mailing
address,
and
an
email
address
or
other
contact
information
in
the
body
of
your
comment.
Also
include
this
contact
information
on
the
outside
of
any
disk
or
CD
ROM
you
submit,
and
in
any
cover
letter
accompanying
the
disk
or
CD
ROM.
This
ensures
that
you
can
be
identified
as
the
submitter
of
the
comment
and
allows
EPA
to
contact
you
in
case
EPA
cannot
read
your
comment
due
to
technical
difficulties
or
needs
further
information
on
the
substance
of
your
comment.
EPA's
policy
is
that
EPA
will
not
edit
your
comment,
and
any
identifying
or
contact
information
provided
in
the
body
of
a
comment
will
be
included
as
part
of
the
comment
that
is
placed
in
the
official
public
docket,
and
made
available
in
EPA's
electronic
public
docket.
If
EPA
cannot
read
your
comment
due
to
technical
difficulties
and
cannot
contact
you
for
clarification,
EPA
may
not
be
able
to
consider
your
comment.
i.
EPA
Dockets.
Your
use
of
EPA's
electronic
public
docket
to
submit
comments
to
EPA
electronically
is
EPA's
preferred
method
for
receiving
comments.
Go
directly
to
EPA
Dockets
at
http://
www.
epa.
gov/
edocket,
and
follow
the
online
instructions
for
submitting
comments.
Once
in
the
system,
select
``
search,''
and
then
key
in
docket
ID
number
OPP
 
2003
 
0211.
The
system
is
an
``
anonymous
access''
system,
which
means
EPA
will
not
know
your
identity,
e­
mail
address,
or
other
contact
information
unless
you
provide
it
in
the
body
of
your
comment.
ii.
E­
mail.
Comments
may
be
sent
by
e­
mail
to
opp­
docket@
epa.
gov,
Attention:
Docket
ID
Number
OPP
 
2003
 
0211.
In
contrast
to
EPA's
electronic
public
docket,
EPA's
e­
mail
system
is
not
an
``
anonymous
access''
system.
If
you
send
an
e­
mail
comment
directly
to
the
docket
without
going
through
EPA's
electronic
public
docket,
EPA's
e­
mail
system
automatically
captures
your
e­
mail
address.
E­
mail
addresses
that
are
automatically
captured
by
EPA's
e­
mail
system
are
included
as
part
of
the
comment
that
is
placed
in
the
official
public
docket,
and
made
available
in
EPA's
electronic
public
docket.
iii.
Disk
or
CD
ROM.
You
may
submit
comments
on
a
disk
or
CD
ROM
that
you
mail
to
the
mailing
address
identified
in
Unit
I.
C.
2.
These
electronic
submissions
will
be
accepted
in
WordPerfect
or
ASCII
file
format.
Avoid
the
use
of
special
characters
and
any
form
of
encryption.
2.
By
mail.
Send
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(
PIRIB)
(
7502C),
Office
of
Pesticide
Programs
(
OPP),
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460
 
0001,
Attention:
Docket
ID
Number
OPP
 
2003
 
0211.
3.
By
hand
delivery
or
courier.
Deliver
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(
PIRIB),
Office
of
Pesticide
Programs
(
OPP),
Environmental
Protection
Agency,
Rm.
119,
Crystal
Mall
#
2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA,
Attention:
Docket
ID
Number
OPP
 
2003
 
0211.
Such
deliveries
are
only
accepted
during
the
docket's
normal
hours
of
operation
as
identified
in
Unit
I.
B.
1.

D.
How
Should
I
Submit
CBI
to
the
Agency?

Do
not
submit
information
that
you
consider
to
be
CBI
electronically
through
EPA's
electronic
public
docket
or
by
e­
mail.
You
may
claim
information
that
you
submit
to
EPA
as
CBI
by
marking
any
part
or
all
of
that
information
as
CBI
(
if
you
submit
CBI
on
disk
or
CD
ROM,
mark
the
outside
of
the
disk
or
CD
ROM
as
CBI
and
then
identify
electronically
within
the
disk
or
CD
ROM
the
specific
information
that
is
CBI).
Information
so
marked
will
not
be
disclosed
except
in
accordance
with
procedures
set
forth
in
40
CFR
part
2.
In
addition
to
one
complete
version
of
the
comment
that
includes
any
information
claimed
as
CBI,
a
copy
of
the
comment
that
does
not
contain
the
information
claimed
as
CBI
must
be
submitted
for
inclusion
in
the
public
docket
and
EPA's
electronic
public
docket.
If
you
submit
the
copy
that
does
not
contain
CBI
on
disk
or
CD
ROM,
mark
the
outside
of
the
disk
or
CD
ROM
clearly
that
it
does
not
contain
CBI.
Information
not
marked
as
CBI
will
be
included
in
the
public
docket
and
EPA's
electronic
public
docket
without
prior
notice.
If
you
have
any
questions
about
CBI
or
the
procedures
for
claiming
CBI,
please
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.

E.
What
Should
I
Consider
as
I
Prepare
My
Comments
for
EPA?

You
may
find
the
following
suggestions
helpful
for
preparing
your
comments:
1.
Explain
your
views
as
clearly
as
possible.
2.
Describe
any
assumptions
that
you
used.
3.
Provide
copies
of
any
technical
information
and/
or
data
you
used
that
support
your
views.
4.
If
you
estimate
potential
burden
or
costs,
explain
how
you
arrived
at
the
estimate
that
you
provide.
5.
Provide
specific
examples
to
illustrate
your
concerns.
6.
Make
sure
to
submit
your
comments
by
the
deadline
in
this
notice.
7.
To
ensure
proper
receipt
by
EPA,
be
sure
to
identify
the
docket
ID
number
assigned
to
this
action
in
the
subject
line
on
the
first
page
of
your
response.
You
may
also
provide
the
name,
date,
and
Federal
Register
citation.

II.
What
Action
is
the
Agency
Taking?

EPA
has
received
pesticide
petitions
as
follows
proposing
the
establishment
and/
or
amendment
of
regulations
for
residues
of
a
certain
pesticide
chemical
in
or
on
various
food
commodities
under
section
408
of
the
Federal
Food,
Drug,
and
Cosmetic
Act
(
FFDCA),
21
U.
S.
C.
346a.
EPA
has
determined
that
these
petitions
contain
data
or
information
regarding
the
elements
set
forth
in
FFDCA
section
408(
d)(
2);
however,
EPA
has
not
fully
evaluated
the
sufficiency
of
the
submitted
data
at
this
time
or
whether
the
data
support
granting
of
the
petitions.
Additional
data
may
be
needed
before
EPA
rules
on
the
petitions.

List
of
Subjects
Environmental
protection,
Agricultural
commodities,
Feed
additives,
Food
additives,
Pesticides
and
pests,
Reporting
and
recordkeeping
requirements.

Dated:
June
20,
2003.
Debra
Edwards,
Director,
Registration
Division,
Office
of
Pesticide
Programs.

Summary
of
Petition
The
petitioner's
summary
of
the
pesticide
petitions
is
printed
below
as
required
by
FFDCA
section
408(
d)(
3).
The
summary
of
the
petitions
was
prepared
by
the
petitioner
and
represents
the
view
of
the
petitioner.
The
petitions
summary
announces
the
availability
of
a
description
of
the
analytical
methods
available
to
EPA
for
the
detection
and
measurement
of
the
pesticide
chemical
residues
or
an
explanation
of
why
no
such
method
is
needed.

Mitsui
Chemicals,
Inc.

PP
2F6427
and
3F6566
EPA
has
received
pesticide
petitions
(
2F6427
and
3F6566)
from
Mitsui
Chemicals,
Inc.,
Chiyoda­
ku,
Tokyo,
Japan,
proposing
pursuant
to
section
408(
d)
of
the
FFDCA,
21
U.
S.
C.
346a(
d),
to
amend
40
CFR
part
180
by
establishing
tolerances
for
residues
of
dinotefuran,
(
RS)­
1­
methyl­
2­
nitro­
3­
(
tetrahydro­
3­
furylmethyl)
guanidine
and
its
major
metabolites,
1­
methyl­
3­
(
tetrahydro­
3­
furylmethyl)
guanidine,

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Vol.
68,
No.
127
/
Wednesday,
July
2,
2003
/
Notices
and
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)­
urea,
in
or
on
fruiting
vegetables,
leafy
vegetables,
head
and
stem
brassica
vegetables,
cotton,
cucurbits,
grapes,
and
potato.
The
tolerances
are
set
at
the
following
value:
Fruiting
vegetables,
0.7
part
per
million
(
ppm);
leafy
vegetables,
5.0
ppm;
tomato
paste,
1.0
ppm;
cucurbits,
0.5
ppm;
head
and
stem
brassica
vegetables,
1.4
ppm;
grape,
0.8
ppm;
raisin,
2.5
ppm;
potato,
0.05
ppm;
chips,
0.10
ppm;
granules,
0.15
ppm;
cotton
seed
undelinted
at
0.2
ppm,
and
cotton
gin
byproducts
at
7.0
ppm.
Tolerances
for
meat,
milk,
and
byproducts
is
set
at
0.05
ppm.
This
new
active
ingredient
has
been
accepted
by
EPA
as
a
reduced
risk
chemical.
EPA
has
determined
that
the
petitions
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
support
granting
of
the
petitions.
Additional
data
may
be
needed
before
EPA
rules
on
the
petitions.

A.
Residue
Chemistry
1.
Plant
metabolism.
The
primary
metabolic
pathways
of
dinotefuran
in
plants
(
rice,
apple,
potato,
oilseed,
rape,
and
lettuce)
were
similar
to
those
described
for
animals,
with
certain
extensions
of
the
pathway
in
plants.
Parent
compound,
dinotefuran,
and
two
metabolites,
1­
methyl­
3­(
tetrahydro­
3­
furymethyl)
guanidine
and
1­
methyl­
3­
(
tetrahydro­
3­
furymethyl)­
urea
were
major
metabolites
in
all
crops.
The
metabolism
of
dinotefuran
in
plants
and
animals
is
understood
for
the
purposes
of
the
proposed
tolerances.
Parent
dinotefuran
and
the
metabolites,
1­
methyl­
3­(
tetrahydro­
3­
furymethyl)
guanidine
and
1­
methyl­
3­
(
tetrahydro­
3­
furymethyl)­
urea
are
the
residues
of
concern
for
tolerance
setting
purposes.
2.
Analytical
method.
Mitsui
Chemicals,
Inc.,
has
submitted
practical
analytical
methodology
for
detecting
and
measuring
levels
of
dinotefuran
and
its
metabolites,
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)
guanidine
and
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)­
urea,
in
or
on
raw
agricultural
commodities
(
RACs).
The
high
performance
liquid
chromotography
(
HPLC)
method
was
validated
for
determination
of,
dinotefuran,
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)
guanidine,
and
1­
methyl­
3­
(
tetrahydro­
3­
furylmethyl)­
urea
in
or
on
tomatoes,
peppers,
cucurbits,
brassica,
grapes,
potatoes,
and
lettuce
for
raw
agricultural
commodity
matrices
and
in
or
on
tomato
paste,
puree,
grape
juice,
raisins,
potato
chips,
granules,
and
wet
peel
for
processed
commodity
matrices.
After
extraction
with
a
water/
acetonitrile
mixture
and
clean
up
with
hexane
and
extraction
columns,
concentrations
of
dinotefuran
and
its
metabolites
were
quantified
after
HPLC
separation
by
mass
spectrometry/
molecular
size
(
MS/
MS)
detection.
The
limit
of
quantitation
(
LOQ)
was
0.01
ppm
for
all
matrices.
The
HPLC
method
was
validated
for
the
determination
of
dinotefuran
and
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)­
urea
in
or
on
cotton
(
undelinted
seed,
gin
trash,
meal,
hulls,
refined
oil),
and
leafy
vegetables.
After
extraction
with
a
water/
acetonitrile
mixture
and
clean
up
dinotefuran,
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)
guanidine,
and
1­
methyl­
3­
(
tetrahydro­
3­
furylmethyl)­
urea
were
quantified
after
HPLC
separation
by
MS/
MS
detection.
For
undelinted
seed,
gin
trash,
meal,
and
hulls,
a
LOQ
of
0.05
milligram/
kilogram
(
mg/
kg)
and
a
working
range
from
0.05
to
0.50
mg/
kg
were
successfully
validated
for
dinotefuran,
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)
guanidine,
and
1­
methyl­
3­
(
tetrahydro­
3­
furylmethyl)­
urea.
For
refined
oil,
a
LOQ
of
0.01
mg/
kg
and
a
working
range
from
0.01
to
0.10
mg/
kg
were
successfully
validated
for
dinotefuran,
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)
guanidine,
and
1­
methyl­
3­
(
tetrahydro­
3­
furylmethyl)­
urea.
An
HPLC
method
was
validated
for
the
determination
of
dinotefuran,
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)
guanidine,
and
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)­
urea,
in
lettuce.
After
extraction
with
water/
acetonitrile
mixture
and
clean­
up,
dinotefuran
was
quantified
after
HPLC
separation
by
ultraviolet
ray
(
UV)
detection,
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)
guanidine,
and
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)­
urea
by
MSD.
A
LOQ
0.010
mg/
kg
and
a
working
range
from
0.01
to
5.00
mg/
kg
were
successfully
validated
from
dinotefuran,
1­
methyl­
3­
(
tetrahydro­
3­
furylmethyl)
guanidine,
and
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)­
urea.
All
of
the
above
methods
have
been
independently
validated.
3.
Magnitude
of
residues.
Crops
in
residue
trials
were
treated
at
maximum
label
rates
and
harvested
at
the
specified
minimum
treatment
to
harvest
intervals.
The
residue
method
for
dinotefuran,
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)
guanidine,
and
1­
methyl­
3­
(
tetrahydro­
3­
furylmethyl)­
urea,
in
all
components
utilized
HPLC
separation
with
MS/
MS
detection.
For
cucurbit
vegetables
(
crop
group
9),
residue
trials
were
conducted
for
each
of
the
three
representative
crops,
cucumbers,
melons,
and
squash.
The
proposed
tolerance
in
or
on
cucurbit
vegetables
for
combined
residues
of
dinotefuran,
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)
guanidine,
and
1­
methyl­
3­
(
tetrahydro­
3­
furylmethyl)­
urea,
is
0.5
ppm.
The
maximum
combined
residue
found
for
the
representative
cucurbit
vegetable
crops
was
0.44
ppm
for
a
melon
sample.
For
leafy
vegetables
(
crop
group
4),
residue
trials
were
conducted
for
each
of
the
four
representative
crops,
celery,
leaf
lettuce,
head
lettuce,
and
spinach,
at
six
locations.
The
proposed
tolerance
in
or
on
leafy
vegetables
for
combined
residues
of
dinotefuran,
1­
methyl­
3­
(
tetrahydro­
3­
furylmethyl)
guanidine,
and
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)­
urea,
is
5.0
ppm.
The
maximum
combined
residue
found
for
the
representative
leafy
vegetable
crops
was
4.36
ppm
for
a
spinach
sample.
Residue
trials
for
cotton
were
conducted
at
13
locations
and
undelinted
cotton
seed
samples
were
collected
and
analyzed.
Cotton
gin
byproducts
(
gin
trash)
samples
were
obtained
for
7
of
the
locations.
Processing
studies
with
analyses
of
cotton
seed
meal,
hulls,
and
oil
were
performed
with
cotton
seed
harvested
at
two
locations
that
were
both
treated
with
5X
the
maximum
label
rate.
The
proposed
tolerance
for
combined
residues
of
dinotefuran,
1­
methyl­
3­
(
tetrahydro­
3­
furylmethyl)
guanidine,
and
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)­
urea,
in
or
on
cotton
seed
undelinted
is
0.2
ppm.
All
cotton
seed
residue
samples
had
combined
residues
of
less
than
0.2
ppm.
The
proposed
tolerance
for
cotton
gin
byproducts
is
7.0
ppm
for
combined
residues
of
dinotefuran
and
its
two
major
metabolites.
The
maximum
combined
residues
for
cotton
gin
byproducts
in
these
trials
was
6.4
ppm.
Processing
studies
established
that
residues
of
dinotefuran
and
its
metabolites,
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)
guanidine,
and
1­
methyl­
3­
(
tetrahydro­
3­
furylmethyl)­
urea,
did
not
concentrate
in
cotton
seed
meal,
oil,
or
hulls.
Therefore,
tolerances
are
not
proposed
for
these
processing
fractions.
Residue
trials
for
grapes
were
conducted
at
13
locations
and
2
grape
juice
and
raisin
processing
studies
were
performed
with
grapes
from
exaggerated
treatment
rate
applications.
The
proposed
tolerance
for
combined
residues
of
dinotefuran,
1­
methyl­
3­
(
tetrahydro­
3­
furylmethyl)
guanidine,
and
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)­
urea,
in
or
on
grapes
is
0.8
ppm.
The
maximum
combined
residue
for
an
individual
grape
residue
sample
was
0.73
ppm
and
the
highest
average
field
trial
(
HAFT)
for
grapes
had
VerDate
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39550
Federal
Register
/
Vol.
68,
No.
127
/
Wednesday,
July
2,
2003
/
Notices
combined
residues
of
0.55
ppm.
The
proposed
tolerance
for
raisins
is
2.5
ppm
for
combined
residues
of
dinotefuran
and
its
two
major
metabolites
based
on
the
average
concentration
factor
of
4.0
for
processing
grapes
to
raisins.
The
grape
juice
processing
studies
established
an
average
concentration
factor
of
1.3
for
residues
of
dinotefuran
and
its
metabolites
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)
guanidine,
and
1­
methyl­
3­
(
tetrahydro­
3­
furylmethyl)­
urea,
because
the
product
of
multiplying
the
grape
HAFT
times
the
average
concentration
factor
for
processing
grapes
into
juice
is
less
than
the
proposed
grape
tolerance,
a
separate
tolerance
is
not
proposed
for
grape
juice.
For
potatoes,
residue
trials
were
performed
at
17
locations
and
2
studies
processing
potatoes
into
chips,
granules,
and
wet
peel
were
performed
with
potatoes
that
were
treated
with
exaggerated
application
rates.
The
proposed
tolerance
for
combined
residues
of
dinotefuran
and
its
metabolites
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)
guanidine,
and
1­
methyl­
3­
(
tetrahydro­
3­
furylmethyl)­
urea,
on
potatoes
is
0.05
ppm.
The
maximum
combined
residues
found
on
potatoes
were
less
than
0.05
ppm
with
maximum
residues
of
dinotefuran
less
than
0.03
ppm.
The
HAFT
result
was
0.04
ppm
of
combined
residues.
The
average
concentration
factors
for
processing
potatoes
into
chips,
granules,
and
wet
peel
were
2.2,
3.65,
and
less
than
1
respectively.
No
separate
tolerance
is
proposed
for
wet
peel.
Based
on
the
average
concentration
factors
and
the
HAFT,
tolerances
for
combined
residues
of
dinotefuran,
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)
guanidine,
and
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)­
urea,
are
proposed
for
potato
chips
at
0.1
ppm
and
for
potato
granules
at
0.15
ppm.
For
fruiting
vegetables
(
crop
group
8)
residue
trials
were
conducted
for
the
three
representative
commodities,
tomatoes,
bell
pepper,
and
non­
bell
pepper.
The
proposed
tolerance
for
combined
residues
of
dinotefuran,
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)
guanidine,
and
1­
methyl­
3­
(
tetrahydro­
3­
furylmethyl)­
urea,
in
or
on
fruiting
vegetables
is
0.7
ppm.
The
maximum
combined
residue
for
the
representative
fruiting
vegetables
was
0.58
ppm
on
peppers.
The
HAFT
result
for
combined
residues
on
tomatoes
was
0.20
ppm.
Three
studies
for
processing
tomatoes
into
tomato
puree
and
tomato
paste
were
performed
with
tomatoes
that
were
treated
at
exaggerated
application
rates.
The
average
concentration
factors
determined
in
these
studies
were
1.8
for
processing
tomatoes
into
puree
and
4.8
for
processing
tomatoes
into
paste.
Since
the
product
of
the
average
concentration
factor
for
puree
and
the
HAFT
for
tomatoes
is
less
than
the
proposed
tolerance
for
fruiting
vegetables,
no
separate
tolerance
is
proposed
for
tomato
puree.
A
combined
tolerance
of
1.0
ppm
is
proposed
for
tomato
paste,
based
on
the
average
concentration
factor
for
processing
of
4.8
and
the
HAFT
of
0.20
ppm
for
tomatoes.
For
vegetables,
brassica
head,
and
stem
crop
subgroup
(
crop
subgroup
5
 
A),
residue
trials
were
conducted
with
three
representative
crops,
broccoli,
cauliflower,
and
cabbage.
The
proposed
tolerance
for
combined
residues
of
dinotefuran,
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)
guanidine,
and
1­
methyl­
3­
(
tetrahydro­
3­
furylmethyl)­
urea,
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)
guanidine,
and
1­
methyl­
3­
(
tetrahydro­
3­
furylmethyl)­
urea,
on
stem
and
head
brassica
vegetables
is
1.4
ppm.
The
maximum
combined
residue
in
field
trials
was
1.25
ppm
on
broccoli.
Metabolism
studies
in
livestock
and
poultry
(
nature
of
residue
studies
with
goats
and
hens),
established
that
dinotefuran
was
rapidly
metabolized
and
excreted
and
that
there
was
very
little
transmittal
of
residues
of
dinotefuran
and
its
metabolites
to
meat,
milk,
or
eggs.
For
goats
fed
10
ppm
of
radiolabeled
dinotefuran,
the
total
radioactive
residues
(
TRR)
in
meat
and
milk
were
less
than
0.05
ppm.
The
maximum
livestock
dietary
burden
from
feeding
cotton
commodities
and
potatoes
(
which
all
contain
residues
at
the
proposed
tolerance
levels)
was
1.9
ppm
for
beef
cattle
and
1.9
ppm
for
dairy
cattle.
To
provide
for
the
possible
transmittal
of
the
residues
of
dinotefuran
and
its
metabolites,
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)
guanidine,
and
1­
methyl­
3­
(
tetrahydro­
3­
furylmethyl)­
urea,
in
cattle
and
other
livestock,
tolerances
are
proposed
for
combined
residues
of
dinotefuran,
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)
guanidine,
and
1­
methyl­
3­
(
tetrahydro­
3­
furylmethyl)­
urea,
in
milk
at
0.05
ppm,
in
meat
(
from
cattle,
goats,
hogs,
horses,
and
sheep)
at
0.05
ppm
and
in
meat
byproducts,
including
fat,
liver,
and
kidney,
(
from
cattle,
goats,
hogs,
horses,
and
sheep)
at
0.05
ppm.
These
proposed
tolerances
are
based
on
the
results
of
a
cow
feeding
study
where
dairy
cows
received
dosages
of
combined
residues
of
dinotefuran
and
its
metabolites
and
1­
methyl­
3­
(
tetrahydro­
3­
furylmethyl)­
urea,
representing
5ppm
(
1X),
15
ppm
(
3X),
and
50
ppm
(
10X)
in
the
daily
diet.
The
dosages
contained
dinotefuran,
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)
guanidine,
and
1­
methyl­
3­
(
tetrahydro­
3­
furylmethyl)­
urea,
in
a
3:
1:
1
ratio,
thus,
the
5
ppm
level
contained
3
ppm
of
dinotefuran,
1
ppm
of
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)
guanidine,
and
1
ppm
of
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)­
urea.
The
dosing
period
was
29
to
30
days,
whole
milk,
skim
milk,
and
cream
were
analyzed
through
the
collection
period
and
meat,
fat,
and
edible
tissues
were
analyzed
at
conclusion
of
the
dosing
period.
There
were
only
low
levels
of
residues
transmitted
to
milk,
meat,
fat,
and
edible
tissues
in
the
study.
No
dinotefuran
residues
(<
0.01
ppm)
were
measured
in
milk
from
5
ppm
dosage
cows.
Maximum
residues
of
dinotefuran
in
milk
were
0.012
ppm
in
the
3X
level
cows
and
0.032
ppm
in
the
10X
level
cows.
No
detectable
residues
of
parent
dinotefuran
were
found
in
muscle,
fat,
or
edible
tissues
from
cows
at
any
dosage
level.
Milk,
muscle,
fat,
and
edible
tissues
were
also
analyzed
for
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)
guanidine,
and
1­
methyl­
3­
(
tetrahydro­
3­
furylmethyl)­
urea,
the
two
dinotefuran
metabolites
included
in
the
combined
residues
in
the
proposed
tolerance
expression.
Transmittal
of
quantifiable
residues
of
1­
methyl­
3­
(
tetrahydro­
3­
furylmethyl)
guanidine
was
found
at
the
1X
dosage
level
with
maximum
residues
of
0.013
ppm
of
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)
guanidine
in
milk
and
at
the
10X
level
with
0.011
ppm
of
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)
guanidine
in
milk
and
0.02
ppm
of
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)
guanidine
in
muscle,
liver,
and
kidney.
Quantifiable
residues
of
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)­
urea
were
found
in
the
1X
dosage
level,
with
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)­
urea
residues
up
to
0.02
ppm
in
whole
milk
and
1­
methyl­
3­
(
tetrahydro­
3­
furylmethyl)­
urea
residues
of
0.011
to
0.012
in
muscle,
liver,
and
kidney.
The
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)­
urea
residues
increased
proportional
to
dosage
with
the
10X
level
having
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)­
urea
residues
of
up
to
0.24
ppm
in
milk,
0.13
ppm
in
muscle,
0.07
ppm
in
fat,
0.12
ppm
in
liver,
and
0.18
ppm
in
kidney.
In
the
cow
feeding
study
at
the
1X
dosage
level
comprising
combined
residues
of
dinotefuran,
1­
methyl­
3­(
tetrahydro­
3­
furylmethyl)
guanidine,
and
1­
methyl­
3­
(
tetrahydro­
3­
furylmethyl)­
urea
of
5
ppm
of
diet,
the
total
combined
residues
for
milk,
muscle,
fat,
liver,
and
kidney
were
each
less
than
0.05
ppm.
Since
the
maximum
theoretical
combined
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Notices
residues
from
the
proposed
uses
of
dinotefuran
on
cotton
and
potatoes
would
be
1.9
ppm,
for
dairy
and
beef
cattle,
the
proposed
tolerances
in
milk,
meat,
and
meat
byproducts,
would
be
sufficient
to
provide
for
potential
transmittal
of
residues
from
livestock
diets
containing
residues
of
dinotefuran
and
its
metabolites.
The
maximum
theoretical
poultry
dietary
burden
from
feeding
cotton
commodities
containing
residues
of
dinotefuran
and
its
metabolites
at
the
proposed
tolerance
levels
was
calculated
to
be
0.09
ppm.
Since
the
TRR
in
meat
and
eggs
from
hens
fed
10
ppm
of
radiolabeled
dinotefuran
in
the
poultry
metabolism
study
was
less
than
0.05
ppm
it
can
be
concluded
that
there
is
no
reasonable
expectation
of
transmittal
of
finite
residues
of
dinotefuran
and
its
metabolites
to
meat
and
eggs,
for
poultry
fed
cotton
commodities
treated
with
dinotefuran.
Therefore
no
tolerances
are
proposed
for
combined
residues
of
dinotefuran
and
its
metabolites
in
poultry
or
eggs.

B.
Toxicological
Profile
1.
Acute
toxicity.
Dinotefuran
has
low
acute
oral,
dermal,
and
inhalation
toxicity.
The
oral
lethal
dose
(
LD)
50
in
rats
is
2,450
mg/
kg,
the
dermal
LD50
is
>
2,000
mg/
kg
and
the
inhalation
4­
hour
lethal
concentration
(
LC)
50
is
>
4.09
milligrams/
Liter
(
mg/
L)
air.
Dinotefuran
is
not
a
skin
sensitizer
in
guinea
pigs,
but
is
slightly
irritating
to
the
skin
and
eyes
of
rabbits.
End­
use
formulations
of
dinotefuran
have
similar
low
acute
toxicity
profiles.
2.
Genotoxicity.
Dinotefuran
and
its
metabolites
do
not
induce
gene
mutations
in
bacterial
and
mammalian
cells,
chromosome
aberrations
in
mammalian
cells
or
deoxyribonucleic
acid
(
DNA)
damage
in
bacterial
cells
in
in
vitro
test
systems.
Similarly,
it
does
not
exhibit
a
clastogenic
effect
in
vivo
in
the
mouse
micronucleus
test.
Therefore,
there
is
no
evidence
to
suggest
a
genotoxic
hazard
at
any
of
the
three
main
levels
of
genetic
organization.
3.
Reproductive
and
developmental
toxicity.
In
rat
and
rabbit
developmental
toxicity
studies
with
dinotefuran,
there
was
no
evidence
of
teratogenicity
or
other
embryotoxic
effects
at
the
highest
dose
levels,
although
maternal
toxicity
was
evident.
There
were
no
treatmentrelated
effects
on
litter
parameters
at
any
dose
level
in
either
species.
In
rats,
1,000
mg/
kg
produced
decreased
food
consumption,
body
weight
gain,
and
increased
water
intake.
In
rabbits,
300
mg/
kg
produced
hypoactivity,
prone
position,
panting,
flushing
of
the
nose
and
ears,
tremors,
reduced
weight
gain,
food
consumption,
and
water
intake.
Necropsy
revealed
pale
brown
discoloration
of
liver
and
gray/
white
plaques
in
the
stomach
at
125
and
300
mg/
kg.
The
no
adverse
effect
level
(
NOAEL)
values
in
maternal
rats
and
rabbits
were
300
and
52
mg/
kg/
day,
respectively.
The
NOAEL
values
in
rats
and
rabbits
for
embryonic
development
and
teratogenicity
were
the
highest
dose
levels
administered,
1,000
and
300
mg/
kg/
day,
respectively.
In
a
2­
generation
study,
parental
animals
of
both
sexes
and
both
generations
showed
reduced
body
weight
gain
and
food
consumption
at
the
highest
dose
level
evaluated
(
10,000
ppm),
but
there
was
no
effect
of
treatment
at
any
dose
level
in
either
generation
on
reproductive
performance
indicators.
There
were
no
treatmentrelated
effects
at
any
dose
level
on
the
histopathological
appearance
of
the
reproductive
organs
of
either
sex.
Similarly,
there
were
no
effects
at
any
dose
level
in
either
generation
on
quantitative
ovarian
histopathology
or
on
sperm
counts,
motility
and
morphology.
Reduced
spleen
weight
in
probit
dose
extrapolation
model
(
P)
generation
animals
and
reduced
thyroid
weight
in
F1
generation
parental
females
were
apparent
at
10,000
ppm.
F1
pup
behavioral
and
sexual
development
was
unaffected
by
treatment
at
all
dose
levels
but
pup
weight
gain
during
lactation
was
reduced
at
10,000
ppm
in
both
generations.
Furthermore,
the
spleen
weight
of
F1
generation
progeny
was
reduced
at
10,000
ppm.
Based
on
reduced
weight
gain
and
food
consumption
in
parental
animals
at
10,000
ppm
and
reduced
pre­
weaning
weight
gain
in
the
offspring,
the
NOAEL
value
for
parental
animals
and
offspring
is
241
mg/
kg.
4.
Subchronic
toxicity.
Dinotefuran
was
evaluated
in
a
13­
week
oral
(
diet)
toxicity
studies
in
rats,
mice,
and
dogs.
No
specific
target
organs
were
identified
in
any
species.
In
the
rat
study,
a
NOAEL
of
500
ppm
(
34/
38
mg/
kg/
day
for
males
and
females)
was
established,
based
on
minimal
growth
retardation
in
females
and
adrenal
cortical
vacuolation
in
males.
A
NOAEL
was
established
at
5,000
ppm
(
336/
384
mg/
kg/
day
for
males/
females)
based
on
marked
growth
retardation
at
25,000
ppm
(
adrenal
cortical
vacuolation
not
adverse).
In
the
mouse
study,
a
NOAEL
of
25,000
ppm
(
4,442/
5,414
mg/
kg/
day
for
males/
females)
was
established
based
on
growth
retardation
at
50,000
ppm.
In
the
dog
study,
a
NOAEL
of
8,000
ppm
(
307/
323
mg/
kg/
day
in
males/
females)
was
established
based
on
growth
retardation.
Dinotefuran
was
also
evaluated
for
dermal
and
inhalation
toxicity
for
4
weeks
in
rats.
Daily
inhalation
exposure
of
rats
for
6
hours/
day
for
4
weeks
did
not
elicit
toxicologically
significant
effects
at
any
exposure
concentration
up
to
and
including
the
highest
technically
achievable
concentration
(
2.08
mg/
L)
with
a
low
mass
median
aerodynamic
diameter)
(
MMAD 
±
GSM
of
2.03
µ
m
±
3.60.
Dinotefuran
was
well
tolerated
and
there
were
no
treatment­
related
effects
on
clinical
condition,
hematology,
and
clinical
chemistry
profiles,
organ
weights,
macroscopic,
and
microscopic
pathology.
Dermal
application
for
4
weeks
at
dose
levels
up
to
1,000
mg/
kg/
day
did
not
elicit
any
local
or
systemic
effects
on
any
of
the
parameters
examined.
Therefore,
no
target
organs
were
identified
in
the
rat
either
by
dermal
or
inhalation
exposure.
5.
Neurotoxicity.
Dinotefuran
did
not
produce
any
functional
or
histomorphological
evidence
of
neurotoxicity
in
acute
(
gavage)
and
13
 
week
(
dietary)
neurotoxicity
studies
in
rats.
The
NOAEL
for
neurotoxicity
in
the
acute
study
was
1,500
mg/
kg,
the
highest
dose
level
administered.
The
NOAEL
for
neurotoxicity
in
the
13
 
week
dietary
study
was
50,000
ppm
(
3,413/
3,806
mg/
kg/
day
for
males
and
females).
The
NOAEL
for
all
effects
in
this
study
was
5,000
ppm
(
327/
400
mg/
kg/
day
for
males
and
females)
based
on
reduced
body
weight
gain
and
food
consumption.
6.
Chronic
toxicity.
Chronic
toxicity
studies
with
dinotefuran
have
been
conducted
in
rats,
mice,
and
dogs.
In
common
with
the
subchronic
studies
in
these
species,
no
specific
target
organs
could
be
identified.
In
the
52­
week
dog
study,
a
NOAEL
of
559/
512
mg/
kg/
day
for
males/
females
was
established
based
on
decreased
weight
gain
in
both
sexes
and
decreased
food
consumption
in
females.
In
the
78­
week
mouse
study,
a
NOAEL
of
345/
441
mg/
kg/
day
for
males/
females
was
established,
based
on
decreased
weight
gain
and
a
decrease
in
circulating
platelet
counts.
In
the
104­
week
rat
study,
a
NOAEL
of
991/
127
mg/
kg/
day
for
males/
females
was
established.
This
was
based
on
a
decrease
in
weight
gain
in
females.
7.
Carcinogenicity.
The
carcinogenic
potential
of
dinotefuran
has
been
evaluated
in
rats
and
mice.
Survival
incidences
in
the
oncogenicity
studies
were
unaffected
by
treatment
at
all
dose
levels.
There
were
no
treatment­
related
effects
on
the
nature
and
incidence
of
neoplastic
and
adverse
non­
neoplastic
histomorphological
findings
in
either
species
at
any
dose
level.
Therefore,
the
NOAEL
values
for
all
effects,
991/
127
mg/
kg/
day
(
male/
female
rats)
and
345/
441
mg/
kg/
day
(
male/
female
mice)
are
based
on
reduced
weight
gain,
and
also
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Notices
on
reduced
numbers
of
platelets
in
mice.
8.
Animal
metabolism.
In
the
rat,
dinotefuran
is
rapidly
and
almost
completely
absorbed
from
the
gastrointestinal
tract
into
the
general
circulation,
and
is
widely
distributed
throughout
the
tissues
and
fluids
of
the
body.
Elimination
is
rapid,
predominantly
by
urinary
excretion
and
almost
complete
within
7
days
of
administration.
There
is
no
evidence
for
tissue
accumulation.
Dinotefuran
is
rapidly
transferred
to
maternal
milk
and
widely
distributed
into
fetal
tissues
but
rapidly
eliminated
from
them.
More
than
90%
of
orally
and
intravenously
administered
dinotefuran
is
eliminated
as
unchanged
parent
molecule,
which
is
also
the
major
radioactive
component
in
plasma,
milk,
bile,
and
most
tissues.
The
major
route
of
metabolism
is
an
initial
enzymatic
hydroxylation
of
the
tetrahydrofuran
ring
to
form
isomers
of
6­
hydroxy­
5­(
2­
hydroxyethyl)­
1­
methyl­
1,3­
diazinane­
2­
ylidine­
N­
nitroamine,
followed
by
further
oxidation,
reduction
and
acetylation
of
6­
hydroxy­
5­(
2­
hydroxyethyl)­
1­
methyl­
1,3­
diazinane­
2­
ylidine­
N­
nitroamine,
to
produce
possible
isomers
of
1­
methyl­
2­
nitro­
3­
(
2­
oxotetrahydro­
3­
furylmethyl)
guanidine,
1­[
4­
hydroxy­
2­
(
hydroxymethyl)
butyl]­
3­
methyl­
2­
nitroguanidine,
6­
hydroxy­
5­(
2­
hydroxyethyl)­
1­
methyl­
1,
3­
diazinane­
2­
ylidene­
N­
nitroamine
acetyl
conjugate
and
3­
hydroxymethyl­
4­
(
3­
methyl­
2­
nitroguanidine)
butyric
acid.
Several
minor
pathways
of
metabolism
of
dinotefuran
were
identified
in
animals.
The
absorption,
distribution,
metabolism
and
elimination
of
dinotefuran
is
unaffected
by
sex
and
treatment
regimen.
In
hens
and
goats,
the
metabolite
profile
was
similar
as
in
plant
metabolism.
9.
Metabolite
toxicology.
The
metabolism
profile
for
dinotefuran
supports
the
use
of
an
analytical
enforcement
method
that
accounts
for
parent
dinotefuran,
and
1­
methyl­
3­
(
tetrahydro­
3­
furymethyl)
guanidine
and
1­
methyl­
3­(
tetrahydro­
3­
furymethyl)­
urea.
Other
metabolites
are
considered
of
equal
or
lesser
toxicity
than
parent
compound.
10.
Endocrine
disruption.
Dinotefuran
does
not
belong
to
a
class
of
chemicals
known
or
suspected
of
having
adverse
effects
on
the
endocrine
system.
There
is
no
evidence
that
dinotefuran
has
any
effect
on
endocrine
function
in
developmental
or
reproduction
studies.
Furthermore,
histological
investigation
of
endocrine
organs
in
chronic
dog,
rat,
and
mouse
studies
did
not
indicate
that
the
endocrine
system
is
targeted
by
dinotefuran.
C.
Aggregate
Exposure
1.
Dietary
exposure.
Chronic
dietary
exposure
assessments
were
conducted
using
a
Tier
I
approach.
This
Tier
I
assessment
incorporated
tolerance
level
residues
and
100%
crop­
treated
in
the
EXP
estimated
dietary
intake
trends
evaluation
system
(
EXPediteTM
system,
Version
4.1).
EXPediteTM
utilized
the
food
consumption
data
derived
from
the
1994
 
1996
U.
S.
Department
of
Agriculture
(
USDA)
Continuing
Surveys
of
Food
Intake
by
Individuals
(
CSFII)
with
the
1998
supplemental
children's
survey.
The
resulting
exposures
were
compared
to
a
RfD
of
1.27
mg/
kg/
day,
which
was
based
on
the
female
NOAEL
of
127
mg/
kg/
day
from
the
104­
week
rat
study
and
a
100
 
fold
uncertainty
factor.
Chronic
dietary
exposure
estimates
for
the
overall
U.
S.
population
and
25
population
subgroups
are
well
below
the
chronic
RfD.
Results
of
these
analyses
are
summarized
below.

TABLE
1.
 
CHRONIC
DIETARY
RISK
(
DEEMTM)
ANALYSIS
OF
DINOTEFURAN
Population
Subgroup
Mg/
Kg
Bwt/
Day
%
RfD
U.
S.
population
0.004109
0.32%

All
infants
(<
1
 
year
old)
0.002815
0.22%

Non­
nursing
infants
0.003438
0.27%

Children
(
1
to
6)
0.007247
0.57%

Children
(
7
to
12)
0.004348
0.34%

Females
(
13
to
50)
0.003350
0.26%

Males
13+
years
0.003173
0.25%

There
are
no
acute
toxicity
concerns
with
dinotefuran
as
there
is
no
toxicological
endpoint
attributable
to
a
single
exposure
in
the
dinotefuran
toxicology
data
base,
including
the
rat
and
rabbit
developmental
studies.
Therefore,
only
chronic
dietary
exposures
have
been
assessed.
2.
Non­
dietary
exposure.
Mitsui
also
requests
registrations
for
the
use
of
dinotefuran
on
cats,
turf,
ornamentals,
indoor
foggers,
and
ready
to
use
sprays.
Mitsui
has
considered
potential
nondietary
and
aggregate
(
non­
dietary
+
dietary)
exposures
to
adults,
adult
females,
and
toddlers
(
1
to
3
years
of
age)
for
these
uses.
Applicator
and
post­
application
exposures
can
result
from
dermal
and
inhalation
routes
for
both
adults
and
toddlers.
Additionally,
toddlers
can
be
exposed
through
the
post­
application
incidental
ingestion
route
via
hand­
tomouth
behavior.
Based
on
the
label
instructions
and
typical
use
patterns
of
these
product
types,
only
short­
term
and
intermediate­
term
exposure
scenarios
should
be
considered
for
dinotefuran
products.
However,
since
there
are
no
toxicological
endpoints
attributable
to
a
single
or
possible
multiple
exposures
in
a
very
short
duration,
as
in
a
short­
term
scenario,
only
the
intermediate­
term
exposure
scenario
has
been
evaluated
for
this
document.
Dermal
exposures
for
applicator
and
post­
application
activities
were
not
assessed
because
the
very
high
dermal
NOAEL
(>
1,000
mg/
kg/
day)
for
dinotefuran
indicates
that
dermal
exposures
are
not
of
concern.
Short­
term
oral
(
e.
g.,
incidental
ingestion)
exposures
for
toddlers,
as
mentioned
above,
were
not
assessed
because
there
are
no
toxicological
endpoints
attributable
to
a
single
exposure
or
multiple
exposures
during
a
very
shortterm
time
frame
in
the
dinotefuran
toxicology
data
base.
Since
the
oral
endpoint
is
used
to
calculate
inhalation
risks,
short­
term
inhalation
exposures
for
toddlers
and
adults
were
also
not
evaluated
since
there
is
no
toxicological
endpoint
attributable
to
a
short­
term
endpoint.
Intermediate­
term
inhalation
exposures
for
applicator
and
postapplication
activities
also
were
not
assessed
because
the
very
high
inhalation
NOAEL
(>
7,000
mg/
kg/
day)
for
dinotefuran
indicates
that
inhalation
exposures
are
not
of
concern.
Therefore,
only
intermediate­
term
oral
(
incidental
ingestion)
exposures
for
toddlers
were
assessed.
These
exposures
were
assessed
for
each
individual
dinotefuran
product,
as
well
as
for
the
aggregation
of
all
products.
In
the
aggregate
assessment,
it
was
assumed
that
the
toddlers
would
be
exposed
to
residues
resulting
from
the
agricultural
uses
(
chronic
dietary),
all
within
1­
day.
These
non­
dietary
assessments
were
conducted
using
equations
and
default
parameters
from
EPA's
Residential
Standard
Operation
Procedures
(
SOPs)
(
EPA,
1997
and
2001)
and
maximum
application
rates.
Although
these
exposures
are
based
on
the
intermediate­
term
time
frame,
the
residue
on
the
day
of
application
was
used
in
the
SOP
equations
in
order
to
maintain
an
extra
level
of
conservatism.
This
assumption
implies
that
the
toddlers
are
exposed
to
residue
levels,
which
are
equivalent
to
levels
resulting
on
the
day
of
application,
every
day
over
an
intermediate­
term
time
frame.
The
resulting
oral
and
aggregate
exposures
were
compared
to
the
NOAEL
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Notices
of
307
mg/
kg/
day
observed
in
the
13­
week
dog
study.
These
risk
estimates
(
margin
of
exposures
(
MOE))
for
toddlers
(
1
to
3
years
of
age)
are
summarized
below.
From
the
results
below,
Mitsui
concludes
there
is
reasonable
certainty
of
no
harm
associated
with
the
aggregate
(
dietary
+
non­
dietary)
exposure
to
dinotefuran.

TABLE
2.
 
INTERMEDIATE­
TERM
AGGREGATE
MOES
Exposure
Routes
Dietary
RTU
Spray
Fogger
Turf
Cat
Aggregate
Toddlers
(
1
to
3
years
old)

Dietary
184,163
NA
NA
NA
NA
184,163
Incidental
Ingestion
NA
23,356
11,431
80,050
1,850
1,410
Total
1,410
3.
Drinking
water
exposure.
EPA
uses
the
drinking
water
level
of
comparison
(
DWLOC)
as
a
theoretical
upper
limit
on
a
pesticide's
concentration
in
drinking
water
when
considering
total
aggregate
exposure
to
a
pesticide
in
food,
drinking
water,
and
residential
uses.
DWLOCs
are
not
regulatory
standards
for
drinking
water;
however,
EPA
uses
DWLOCs
in
the
risk
assessment
process
as
a
surrogate
measure
of
potential
exposure
from
drinking
water.
In
the
absence
of
monitoring
data
for
pesticides,
it
is
used
as
a
point
of
comparison
against
conservative
model
estimates
of
a
pesticides
concentration
in
water.
An
estimate
of
the
drinking
water
environmental
concentration
(
DWEC)
in
ground
water
and
surface
water
for
dinotefuran
has
been
made
for
this
notice
of
filing.
The
DWEC
of
dinotefuran
in
ground
water
was
estimated
to
be
0.94
part
per
billion
(
ppb)
using
screening
concentration
in
ground
water
(
SCI
 
GROW)
(
the
screening
model
for
ground
water),
and
the
DWEC
for
surface
water
was
estimated
to
be
6.24
ppb
(
for
chronic
and
intermediate­
term
aggregate
assessments)
using
FQPA
Index
Reservoir
Screening
Tool
(
FIRST).
To
calculate
the
DWLOC
for
chronic
aggregate
exposure
relative
to
a
chronic
toxicity
endpoint,
the
chronic
dietary
food
exposure
from
EXPediteTM,
as
addressed
above,
was
subtracted
from
the
reference
dose
(
RfD)
to
obtain
the
acceptable
chronic
exposure
to
dinotefuran
in
drinking
water.
DWLOCs,
as
presented
below,
were
then
calculated
using
default
body
weights
and
drinking
water
consumption
figures.

TABLE
3.
 
CHRONIC
AGGREGATE
DRINKING
WATER
ASSESSMENT
Population
Subgroup
Dietary
Mg/
Kg
Bwt/
Day
Maximum
Water
Exposure
Mg/
Kg
Bwt/
Day
Kg
Bwt
SCI
 
GROW
(
ppb)
FIRST
(
ppb)
DWLOC
(
ppb)

U.
S.
population
0.004109
1.265891
70
0.94
6.24
44,306
All
infants
(<
1
 
year
old)
0.002815
1.267185
10
0.94
6.24
12,672
Non­
nursing
infants
0.003438
1.266562
10
0.94
6.24
12,666
Children
(
1
to
6)
0.007247
1.262753
20
0.94
6.24
25,255
Children
(
7
to
12)
0.004348
1.265652
40
0.94
6.24
50,626
Females
(
13
to
50)
0.003350
1.266650
60
0.94
6.24
38,000
Males
(
13+
years)
0.003173
1.266827
70
0.94
6.24
44,339
Chronic
RfD
used
in
assessments
­
1.27
mg/
kg
bwt/
day
The
estimated
average
concentration
of
dinotefuran
in
surface
water
is
6.24
ppb.
This
value
is
less
than
the
lowest
DWLOC
for
dinotefuran
as
a
contribution
to
chronic
aggregate
exposure
(
12,666
ppb
for
non­
nursing
infants,
the
most
highly
exposed
population
group
for
the
chronic
scenario).
Therefore,
taking
into
account
the
proposed
uses,
it
can
be
concluded
with
reasonable
certainty
that
residues
of
dinotefuran
in
food
and
drinking
water
will
not
result
in
unacceptable
levels
of
human
health
risk.
To
calculate
the
DWLOC
for
the
intermediate­
term
aggregate
exposure
relative
to
a
sub­
chronic
toxicity
endpoint,
the
chronic
dietary
food
exposure
from
EXPediteTM
plus
the
intermediate­
term
non­
dietary
exposures
were
subtracted
from
the
NOAEL,
divided
by
the
target
MOE
(
100),
to
obtain
the
acceptable
intermediate­
term
exposure
to
dinotefuran
in
drinking
water.
DWLOCs,
as
presented
below,
were
then
calculated
using
default
body
weights
and
drinking
water
consumption
figures.

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Notices
TABLE
4.
 
INTERMEDIATE­
TERM
AGGREGATE
DRINKING
WATER
ASSESSMENT
Population
Subgroup
NOAEL/
MOE
Mg/
Kg/
Day
Aggregate
Exposure
Mg/
Kg/
Day
Maximum
Water
Exposure
mg/
kg/
day
SCI
 
GROW
(
ppb)
FIRST
(
ppb)
DWLOC
(
ppb)

Toddlers
(
1
to
3)
1
0.307
0.217
2.852
0.94
6.24
42,785
1
Assume
70kg
bodyweight
The
estimated
average
concentration
of
dinotefuran
in
surface
water
is
6.24
ppb.
This
value
is
less
than
the
DWLOC
for
dinotefuran
as
a
contribution
to
intermediate­
term
aggregate
exposure
(
42,785
ppb).
Therefore,
taking
into
account
the
proposed
uses,
it
can
be
concluded
with
reasonable
certainty
that
residues
of
dinotefuran
in
residential
environments
and
in
food
and
drinking
water
will
not
result
in
unacceptable
levels
of
human
health
risk.

D.
Cumulative
Effects
The
potential
for
cumulative
effects
of
dinotefuran
and
other
substances
that
have
a
common
mechanism
of
toxicity
has
also
been
considered.
Dinotefuran
belongs
to
a
pesticide
chemical
class
known
as
the
neonicotinoids
and
subclass
nitroguanadines.
There
is
no
reliable
information
to
indicate
that
toxic
effects
produced
by
dinotefuran
would
be
cumulative
with
those
of
any
other
chemical
including
another
pesticide.
Therefore,
Mitsui
believes
it
is
appropriate
to
consider
only
the
potential
risks
of
dinotefuran
in
an
aggregate
risk
assessment.

E.
Safety
Determinations
1.
U.
S.
population.
Using
the
chronic
exposure
assumptions
and
the
proposed
RfD
described
above,
the
dietary
exposure
to
dinotefuran
for
the
U.
S.
population
(
48
states,
all
seasons)
was
calculated
to
be
0.32%
of
the
RfD
of
1.27
mg/
kg/
day.
The
resulting
DWLOC,
44,306
ppb,
is
much
greater
than
the
estimated
average
concentration
of
dinotefuran
in
surface
water,
6.24
ppb.
Therefore,
taking
into
account
the
proposed
uses,
it
can
be
concluded
with
reasonable
certainty
that
residues
of
dinotefuran
in
residential
environments
and
in
food
and
drinking
water
will
not
result
in
unacceptable
levels
of
human
health
risk.
2.
Infants
and
children.
FFDCA
section
407
provides
that
EPA
shall
apply
an
additional
safety
factor
for
infants
and
children
to
account
for
prenatal
and
postnatal
toxicity
and
the
completeness
of
the
data
base.
Only
when
there
is
no
indication
of
increased
sensitivity
of
infants
and
children
and
when
the
data
base
is
complete,
may
the
extra
safety
factor
be
removed.
In
the
case
of
dinotefuran,
the
toxicology
data
base
is
complete.
There
is
no
indication
of
increased
sensitivity
in
the
data
base
overall,
and
specifically,
there
is
no
indication
of
increased
sensitivity
in
the
developmental
and
multi­
generation
reproductive
toxicity
studies.
Therefore,
Mitsui
concludes
that
there
is
no
need
for
an
additional
safety
factor;
the
RfD
of
1.27
mg/
kg/
day
and
sub­
chronic
NOAEL
of
307
mg/
kg/
day
are
protective
of
infants
and
children.
Using
the
chronic
exposure
assumptions
and
the
proposed
RfD
described
above,
the
dietary
exposure
to
dinotefuran
for
infants
and
children
(
1
to
6
years)
was
calculated
to
be
0.57%
of
the
reference
dose
of
1.27
mg/
kg
bwt/
day.
The
resulting
DWLOC
for
nonnursing
infants,
12,666
ppb,
is
much
greater
than
the
estimated
average
concentration
of
dinotefuran
in
surface
water,
6.24
ppb.
Using
the
intermediate­
term
exposure
assumptions
and
the
proposed
NOAEL
described
above,
the
intermediate­
term
aggregate
exposure
to
dinotefuran
for
the
toddlers
(
1
to
3
years)
resulted
in
an
MOE
of
1,410.
The
resulting
DWLOC,
42,785
ppb,
is
much
greater
than
the
estimated
average
concentration
of
dinotefuran
in
surface
water,
6.24
ppb.
Therefore,
taking
into
account
the
proposed
uses,
it
can
be
concluded
with
reasonable
certainty
that
residues
of
dinotefuran
in
residential
environments
and
in
food
and
drinking
water
will
not
result
in
unacceptable
levels
of
human
health
risk.

F.
International
Tolerances
No
codex
maximum
residue
levels
have
been
established
for
residues
of
dinotefuran
on
any
crops
at
this
time.

[
FR
Doc.
03
 
16737
Filed
7
 
1
 
03;
8:
45
am]

BILLING
CODE
6560
 
50
 
S
ENVIRONMENTAL
PROTECTION
AGENCY
[
OPP
 
2003
 
0226;
FRL
 
7315
 
2]

Copper
Hydroxide;
Notice
of
Filing
of
a
Pesticide
Petition
to
Establish
a
Tolerance
for
a
Certain
Pesticide
Chemical
in
or
on
Food
AGENCY:
Environmental
Protection
Agency
(
EPA).
ACTION:
Notice.

SUMMARY:
This
notice
announces
the
initial
filing
of
a
pesticide
petition
proposing
the
establishment
of
regulations
for
residues
of
a
certain
pesticide
chemical
in
or
on
various
food
commodities.
DATES:
Comments,
identified
by
docket
ID
number
OPP
 
2003
 
0226,
must
be
received
on
or
before
August
1,
2003.
ADDRESSES:
Comments
may
be
submitted
electronically,
by
mail,
or
through
hand
delivery/
courier.
Follow
the
detailed
instructions
as
provided
in
Unit
I.
of
the
SUPPLEMENTARY
INFORMATION.

FOR
FURTHER
INFORMATION
CONTACT:
Kathryn
Boyle,
Registration
Division
(
7505C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460
 
0001;
telephone
number:
(
703)
305
 
6304;
e­
mail
address:
boyle.
kathryn@
epa.
gov.

SUPPLEMENTARY
INFORMATION:

I.
General
Information
A.
Does
this
Action
Apply
to
Me?

You
may
be
potentially
affected
by
this
action
if
you
are
an
agricultural
producer,
food
manufacturer,
or
pesticide
manufacturer.
Potentially
affected
entities
may
include,
but
are
not
limited
to:
 
Crop
production
(
NAICS
code
111)
 
Animal
production
(
NAICS
code
112)
 
Food
manufacturing
(
NAICS
code
311)
 
Pesticide
manufacturing
(
NAICS
code
32532)
This
listing
is
not
intended
to
be
exhaustive,
but
rather
provides
a
guide
for
readers
regarding
entities
likely
to
be
affected
by
this
action.
Other
types
of
entities
not
listed
in
this
unit
could
also
be
affected.
The
North
American
Industrial
Classification
System
(
NAICS)
codes
have
been
provided
to
assist
you
and
others
in
determining
whether
this
action
might
apply
to
certain
entities.
If
you
have
any
questions
regarding
the
applicability
of
this
action
to
a
particular
entity,
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.

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