10469
Federal
Register
/
Vol.
68,
No.
43
/
Wednesday,
March
5,
2003
/
Notices
iv.
Pet
treatment.
Human
exposure
from
the
use
of
imidacloprid
to
treat
dogs
and
cats
for
fleas
has
been
addressed
by
EPA
with
the
conclusion
that
due
to
the
fact
that
imidacloprid
is
not
an
inhalation
or
dermal
toxicant
and
that
while
dermal
absorption
data
are
not
available,
imidacloprid
is
not
considered
to
present
a
hazard
via
the
dermal
route.

D.
Cumulative
Effects
Imidacloprid
is
a
chloronicotinyl
insecticide.
At
this
time,
EPA
has
not
made
a
determination
that
imidacloprid
and
other
substances
that
may
have
a
common
mechanism
of
toxicity
would
have
cumulative
effects.
Therefore,
for
these
tolerance
petitions,
it
is
assumed
that
imidacloprid
does
not
have
a
common
mechanism
of
toxicity
with
other
substances
and
only
the
potential
risks
of
imidacloprid
in
its
aggregate
exposure
are
considered.

E.
Safety
Determination
1.
U.
S.
population.
EPA
has
considered
data
from
developmental
toxicity
studies
in
the
rat
and
rabbit
and
a
2­
generation
reproduction
study
in
the
rat.
These
studies
are
discussed
under
section
A
(
Toxicology
Profile)
above.
The
developmental
toxicity
data
demonstrated
no
increased
sensitivity
of
rats
or
rabbits
to
in
utero
exposure
to
imidacloprid.
In
addition,
the
multigeneration
reproductive
toxicity
study
did
not
identify
any
increased
sensitivity
of
rats
to
in
utero
or
postnatal
exposure.
Parental
NOAELs
were
lower
or
equivalent
to
developmental
or
offspring
NOAELs.
The
developmental
toxicity
studies
are
designed
to
evaluate
adverse
effects
on
the
developing
organism
resulting
from
maternal
pesticide
exposure
during
gestation.
Reproduction
studies
provide
information
relating
to
effects
from
exposure
to
the
pesticide
on
the
reproductive
capability
of
mating
animals
and
data
on
systemic
toxicity.
FFDCA
section
408
provides
that
EPA
shall
apply
an
additional
tenfold
margin
of
safety
for
infants
and
children
in
the
case
of
threshold
effects
to
account
for
prenatal
and
postnatal
toxicity
and
the
completeness
of
the
data
base
unless
EPA
determines
that
a
different
MOS
will
be
safe
for
infants
and
children.
MOS
are
incorporated
into
EPA
risk
assessments
either
directly
through
use
of
a
MOE
analysis
or
through
using
uncertainty
(
safety)
factors
(
UF)
in
calculating
a
dose
level
that
poses
no
appreciable
risk
to
humans.
EPA
believes
that
reliable
data
support
using
the
standard
UF
(
usually
100
for
combined
inter­
species
and
intraspecies
variability)
and
not
the
additional
tenfold
MOE/
UF
when
EPA
has
a
complete
data
base
under
existing
guidelines
and
when
the
severity
of
the
effect
in
infants
or
children
or
the
potency
or
unusual
toxic
properties
of
a
compound
do
not
raise
concerns
regarding
the
adequacy
of
the
standard
MOE/
UF.
Although
developmental
toxicity
studies
showed
no
increased
sensitivity
in
fetuses
as
compared
to
maternal
animals
following
in
utero
exposures
in
rats
and
rabbits,
no
increased
sensitivity
in
pups
as
compared
to
adults
was
seen
in
the
2­
generation
reproduction
toxicity
study
in
rats,
and
the
toxicology
data
base
is
complete
as
to
core
requirements,
EPA
has
determined
that
the
additional
safety
factor
for
the
protection
of
infants
and
children
will
be
retained
but
reduced
to
3x
based
on
the
following
weight­
of­
the­
evidence
considerations
relating
to
potential
sensitivity
and
completeness
of
the
data:
i.
There
is
concern
for
structure
activity
relationship.
Imidacloprid,
a
chloronicotinyl
compound,
is
an
analog
to
nicotine
and
studies
in
the
published
literature
suggests
that
nicotine,
when
administered
causes
developmental
toxicity,
including
functional
deficits,
in
animals
and/
or
humans
that
are
exposed
in
utero.
ii.
There
is
evidence
that
imidacloprid
administration
causes
neurotoxicity
following
a
single
oral
dose
in
the
acute
study
and
alterations
in
brain
weight
in
rats
in
the
2
 
year
carcinogenicity
study.
iii.
The
concern
for
structure
activity
relationship
along
with
the
evidence
of
neurotoxicity
dictates
the
need
of
a
developmental
neurotoxicity
study
for
assessment
of
potential
alterations
on
functional
development.
Because
a
developmental
neurotoxicity
study
potentially
relates
to
both
acute
and
chronic
effects
in
both
the
mother
and
the
fetus,
EPA
has
applied
the
additional
UF
for
FQPA
for
all
population
subgroups,
and
in
both
acute
and
chronic
risk
assessments.
Based
on
the
exposure
assessments
described
above
and
on
the
completeness
and
reliability
of
the
toxicity
data,
it
can
be
concluded
that
the
dietary
exposure
estimates
from
all
label
and
pending
uses
of
imidacloprid
are
7.73%
of
the
aPAD
at
the
99.9th
percentile
and
1.4%
of
the
cPAD
for
the
U.
S.
population.
Thus,
it
can
be
concluded
that
there
is
a
reasonable
certainty
that
no
harm
will
result
from
aggregate
exposure
to
imidacloprid
residues.
2.
Infants
and
children.
Based
on
the
exposure
assessments
described
above
for
the
safety
determination
of
the
U.
S.
population
and
on
the
completeness
and
reliability
of
the
toxicity
data,
it
can
be
concluded
that
the
dietary
exposure
estimates
from
all
label
and
pending
uses
of
imidacloprid
are
16.42%
of
the
aPAD
at
the
99.9th
percentile
and
3.0%
of
the
cPAD
for
the
most
sensitive
population
subgroup,
children
1
 
6
years.
Thus,
it
can
be
concluded
that
there
is
a
reasonable
certainty
that
no
harm
will
result
from
aggregate
exposure
to
imidacloprid
residues.

F.
International
Tolerances
No
CODEX
Maximum
Residue
Levels
have
been
established
for
residues
of
imidacloprid
on
any
crops
pending
in
EPA's
2003
work
plan.
[
FR
Doc.
03
 
5034
Filed
3
 
4
 
03;
8:
45
am]

BILLING
CODE
6560
 
50
 
S
ENVIRONMENTAL
PROTECTION
AGENCY
[
OPP
 
2003
 
0047;
FRL
 
7294
 
5]

Trifloxystrobin;
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
 
0047,
must
be
received
on
or
before
April
4,
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:
Sidney
Jackson,
Registration
Division
(
7505C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460
 
0001;
telephone
number:
(
703)
305
 
7610;
e­
mail
address:
jackson.
sidney@
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:

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Federal
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/
Vol.
68,
No.
43
/
Wednesday,
March
5,
2003
/
Notices
 
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.
To
determine
whether
you
or
your
business
may
be
affected
by
this
action,
you
should
carefully
examine
the
applicability
provisions
in
OPP
 
2003
 
0047.
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
 
0047.
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
the
EPA
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
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
 
0047.
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
 
0047.
In
contrast
to
EPA's
electronic
public
docket,
EPA's
e­
mail
system
is
not
an
``
anonymous
access''

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Federal
Register
/
Vol.
68,
No.
43
/
Wednesday,
March
5,
2003
/
Notices
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
 
0047.
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
 
0047.
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
a
pesticide
petition
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
this
petition
contains
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
petition.
Additional
data
may
be
needed
before
EPA
rules
on
the
petition.

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

Dated:
February
21,
2003.
Peter
Caulkins,
Acting
Director,
Registration
Division,
Office
of
Pesticide
Programs.

Summary
of
Petition
The
petitioner's
summary
of
the
pesticide
petition
is
printed
below
as
required
by
FFDCA
section
408(
d)(
3).
The
summary
of
the
petition
was
prepared
by
the
petitioner
and
represents
the
view
of
the
petitioner.
The
petition
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.
The
Interregional
Research
Project
No.
4
(
IR
 
4)
assembled
and
submitted
the
petition
to
EPA
in
behalf
of
Bayer
CropScience,
the
registrant.

Interregional
Research
Project
Number
4
and
Bayer
CropScience
PP
3E6522
EPA
has
received
a
pesticide
petition
(
3E6522)
from
Interregional
Research
Project
Number
4
(
IR
 
4),
681
U.
S.
Highway
#
1
South,
North
Brunswick,
NJ
08902
 
3390
proposing,
pursuant
to
section
408(
d)
of
the
FFDCA,
21
U.
S.
C.
346a(
d),
to
amend
40
CFR
180.555
by
establishing
a
tolerance
for
residues
of
trifloxystrobin
in
or
on
the
raw
agricultural
commodities
(
RACs)
vegetable,
root,
except
sugar
beet,
subgroup
1B,
except
radish
at
0.1
part
per
million
(
ppm)
and
leafy
petiole
subgroup
4B
at
2.0
ppm.
EPA
has
determined
that
the
petition
contain
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
petition.
Additional
data
may
be
needed
before
EPA
rules
on
the
petition.

A.
Residue
Chemistry
1.
Plant
metabolism.
The
metabolism
of
trifloxystrobin
in
plants
(
cucumbers,
apples,
wheat,
sugar
beets,
and
peanuts),
is
well
understood.
Identified
metabolic
pathways
are
substantially
similar
in
plants
and
animals
(
goat,
rat,
and
hen).
EPA
has
determined
that
trifloxystrobin
parent
and
its
metabolite
CGA
 
321113
are
the
residues
of
concern
for
tolerance
setting
purposes.
2.
Analytical
method.
A
practical
analytical
methodology
for
detecting
and
measuring
levels
of
trifloxystrobin
in
or
on
RACs
has
been
submitted.
The
limit
of
detection
(
LOD)
for
each
analyte
of
this
method
is
0.08
nanogram
(
ng)
injected,
and
the
limit
of
quantitation
(
LOQ)
is
0.02
ppm.
The
method
is
based
on
crop
specific
cleanup
procedures
and
determination
by
gas
chromatography
(
GC)
with
nitrogen­
phosphorus
detection.
3.
Magnitude
of
residues
 
i.
Vegetable
root,
except
sugar
beet,
subgroup
1B,
except
radish.
Interregional
Research
Project
Number
4
received
a
request
from
Michigan
for
the
use
of
trifloxystrobin
on
carrots.
Interregional
Research
Project
Number
4
performed
VerDate
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Federal
Register
/
Vol.
68,
No.
43
/
Wednesday,
March
5,
2003
/
Notices
10
field
trials
to
support
the
requested
tolerance
of
0.1
ppm.
ii.
Leaf
petiole
subgroup
4B.
Interregional
Research
Project
Number
4
received
a
request
from
Florida,
Michigan,
Oregon,
California,
and
Ohio,
for
the
use
of
trifloxystrobin
on
celery.
Interregional
Research
Project
Number
4
performed
nine
field
trials
to
support
the
requested
tolerance
of
2.0
ppm.

B.
Toxicological
Profile
1.
Acute
toxicity.
Studies
conducted
with
the
technical
material
of
trifloxystrobin:
 
Rat.
Acute
oral
toxicity
study
with
a
lethal
dose
(
LD)
50
>
5,000
milligrams/
kilogram
(
mg/
kg).
 
Mouse.
Acute
oral
toxicity
study
with
a
LD50
>
5,000
mg/
kg.
 
Rabbit.
Acute
dermal
toxicity
study
with
a
LD50
>
2,000
mg/
kg.
 
Rat.
Acute
dermal
toxicity
study
with
a
LD50
>
2,000
mg/
kg.
 
Rat.
Acute
inhalation
toxicity
study
with
a
lethal
concentration
(
LC)
50
>
4.65
milligrams/
liter
(
mg/
L).
 
Rabbit.
Eye
irritation
study
showing
slight
irritation
(
toxicity
category
III).
 
Rabbit.
Dermal
irritation
study
showing
slight
irritation
(
toxicity
category
IV).
 
Guinea
pig.
Dermal
sensitization
study
with
the
Buehler's
method
showing
negative
findings.
 
Guinea
pig.
Dermal
sensitization
study
with
the
maximization
method
showing
some
positive
findings.
2.
Genotoxicity.
No
genotoxicity
activity
is
expected
of
trifloxystrobin
under
in
vivo
or
physiological
conditions.
The
compound
has
been
tested
for
its
potential
to
induce
gene
mutation
and
chromosomal
changes
in
five
different
test
systems.
The
only
positive
finding
was
seen
in
the
in
vitro
test
system
(
chinese
hamster
V79
cells)
as
a
slight
increase
in
mutant
frequency
at
a
very
narrow
range
(
250
 
278
micrograms/
milliliter
(
µ
g/
ml)
of
cytologic
and
precipitating
concentrations
(
compound
solubility
in
water
was
reported
to
be
0.61
µ
g/
ml;
precipitate
was
visually
noted
in
culture
medium
at
150
µ
g/
ml).
The
chemical
was
found
to
be
non­
mutagenic
in
the
in
vivo
system
or
all
other
in
vitro
systems.
Consequently,
the
limited
gene
mutation
activity
in
the
V79
cell
line
is
considered
a
nonspecific
effect
under
non­
physiological
in
vitro
conditions
and
not
indicative
of
a
real
mutagenic
hazard.
3.
Reproductive
and
developmental
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
prenatal
and
postnatal
toxicity
and
the
completeness
of
the
data
base.
Based
on
the
current
toxicological
data
requirements,
the
data
base
on
trifloxystrobin
relative
to
prenatal
and
postnatal
effects
for
children
is
complete.
In
assessing
the
potential
for
additional
sensitivity
of
infants
and
children
to
residues
of
trifloxystrobin,
data
were
considered
from
teratogenicity
studies
in
the
rat,
rabbit,
and
a
2
 
generation
reproduction
studies
in
the
rat.
The
teratogenicity
studies
are
designed
to
evaluate
adverse
effects
on
the
developing
embryo
as
a
result
of
chemical
exposure
during
the
period
of
organogenesis.
Reproduction
studies
provide
information
on
effects
from
chemical
exposure
on
the
reproductive
capability
of
mating
animals
and
systemic
and
developmental
toxicity
from
in
utero
exposure.
In
the
rat
teratology
study,
reductions
in
body
weight
gain
and
food
consumption
were
observed
in
the
dam
at
 
100
mg/
kg.
No
teratogenic
effects
or
any
other
effects
were
seen
on
pregnancy
or
fetal
parameters
except
for
the
increased
incidence
of
enlarged
thymus,
which
is
a
type
of
variation,
at
1,000
mg/
kg.
The
developmental
no
observed
adverse
effect
level
(
NOAEL)
was
100
mg/
kg.
In
the
rabbit
teratology
study,
body
weight
loss
and
dramatically
reduced
food
consumption
were
observed
in
the
dam
at
 
250
mg/
kg.
No
teratogenic
effects
or
any
other
effects
were
seen
on
pregnancy
or
fetal
parameters
except
for
the
increase
in
skeletal
anomaly
of
fused
sternebrae
 
3
and
 
4
at
the
top
dose
level
of
500
mg/
kg.
This
finding
is
regarded
as
a
marginal
effect
on
skeletal
development
that
could
have
resulted
from
the
40
 
65%
lower
food
intake
during
treatment
at
this
dose
level.
The
developmental
NOAEL
was
250
mg/
kg.
In
the
2
 
generation
rat
reproduction
study,
body
weight
gain
and
food
consumption
were
decreased
at
 
750
ppm,
especially
in
females
during
lactation.
Consequently,
the
reduced
pup
weight
gain
during
lactation
( 
750
ppm)
and
the
slight
delay
in
eye
opening
(
1,500
ppm)
are
judged
to
be
a
secondary
effect
of
maternal
toxicity.
No
other
fetal
effects
or
any
reproductive
changes
were
noted.
The
low
developmental
NOAEL,
50
ppm
(
5
mg/
kg),
seen
in
this
study
was
probably
due
to
the
lack
of
intermediate
dose
levels
between
50
and
750
ppm.
Based
on
an
evaluation
of
the
dose­
response
relationship
for
pup
weight
at
750
ppm
and
1,500
ppm,
the
NOAEL
should
have
been
nearly
ten­
fold
higher
if
such
a
dose
was
available.
Based
on
all
these
teratology
and
reproduction
studies,
the
lowest
NOAEL
for
developmental
toxicity
is
5
mg/
kg
while
the
lowest
NOAEL
in
the
subchronic
and
chronic
studies
is
2.5
mg/
kg/
day
(
from
the
rat
chronic
study).
Therefore,
no
additional
sensitivity
for
infants
and
children
to
trifloxystrobin
is
suggested
by
the
data
base.
4.
Subchronic
toxicity.
In
subchronic
studies,
several
mortality
related
changes
were
reported
for
the
top
dose
in
dogs
(
500
mg/
kg)
and
rats
(
800
mg/
kg).
At
these
dose
levels,
excessive
toxicity
has
resulted
in
body
weight
loss
and
mortality
with
the
associated
and
nonspecific
changes
in
several
organs
(
such
as
atrophy
in
the
thymus,
pancreas,
bone
marrow,
lymph
node,
and
spleen)
which
are
not
considered
specific
target
organs
for
the
test
compound.
In
the
dog,
specific
effects
were
limited
to
hepatocellular
hypertrophy
at
 
150
mg/
kg
and
hyperplasia
of
the
epithelium
of
the
gall
bladder
at
500
mg/
kg.
Target
organ
effects
in
the
rat
were
noted
as
hepatocellular
hypertrophy
( 
200
mg/
kg)
and
the
related
liver
weight
increase
( 
50
mg/
kg).
In
the
mouse,
target
organ
effects
included
single
cell
necrosis
( 
300
mg/
kg)
and
hypertrophy
(
1,050
mg/
kg)
in
the
liver
and
extramedullary
hematopoiesis
( 
300
mg/
kg)
and
hemosiderosis
in
the
spleen
(
1,050
mg/
kg).
In
general,
definitive
target
organ
toxicity,
mostly
in
the
liver,
was
seen
at
high
feeding
levels
of
over
100
mg/
kg
for
an
extended
treatment
period.
At
the
lowest
observed
adverse
effect
level
(
LOAEL),
no
serious
toxicity
was
observed
other
than
mostly
non­
specific
effects
including
a
reduction
in
body
weight
and
food
consumption
or
liver
hypertrophy.
5.
Chronic
toxicity.
The
liver
appears
to
be
the
major
primary
target
organ
based
on
the
chronic
studies
conducted
in
mice,
rats,
and
dogs.
It
was
identified
as
a
target
organ
in
both
the
mouse
and
the
dog
studies
with
trifloxystrobin.
However,
no
liver
effect
was
seen
in
the
chronic
rat
study
which
produced
the
lowest
NOAEL
of
2.5
mg/
kg
based
on
reduced
body
weight
gain
and
food
consumption
seen
at
higher
dose
levels.
The
compound
did
not
cause
any
treatment­
related
increase
in
general
tumor
incidence,
any
elevated
incidence
of
rare
tumors,
or
shortened
time
to
the
development
of
palpable
or
rapidly
lethal
tumors
in
the
18
 
month
mouse
and
the
24
 
month
rat
studies.
Dosages
in
both
studies
were
sufficient
for
identifying
a
cancer
risk.
In
the
absence
of
carcinogenicity,
a
reference
dose
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10473
Federal
Register
/
Vol.
68,
No.
43
/
Wednesday,
March
5,
2003
/
Notices
(
RfD)
approach
is
appropriate
for
quantitation
of
human
risks.
6.
Animal
metabolism.
Trifloxystrobin
is
moderately
absorbed
from
the
gastrointestinal
tract
of
rats
and
is
rapidly
distributed.
Subsequent
to
a
single
oral
dose,
the
half
life
of
elimination
is
about
2
days
and
excretion
is
primarily
via
bile.
Trifloxystrobin
is
extensively
metabolized
by
the
rat
into
about
35
metabolites,
but
the
primary
actions
are
on
the
methyl
ester
(
hydrolysis
into
an
acid),
the
methoxyimino
group
(
Odemethylation
and
the
methyl
side
chain
(
oxidation
to
a
primary
alcohol).
Metabolism
is
dose
dependent
as
it
was
almost
complete
at
low
doses
but
only
about
60%
complete
at
high
doses.
In
the
goat,
elimination
of
orally
administered
trifloxystrobin
is
primarily
via
the
feces.
The
major
residues
were
the
parent
compound
and
the
acid
metabolite
(
CGA
 
321113)
plus
its
conjugates.
In
the
hen,
trifloxystrobin
is
found
as
the
major
compound
in
tissues
and
in
the
excreta,
but
hydroxylation
of
the
trifluormethyl­
phenyl
moiety
and
other
transformations,
including
methyl
ester
hydrolysis
and
demethylation
of
the
methoxyimino
group,
are
also
seen.
In
conclusion,
the
major
pathways
of
metabolism
in
the
rat,
goat,
and
hen
are
the
same.
7.
Metabolite
toxicology.
Metabolism
of
trifloxystrobin
has
been
well
characterized
in
plants,
soil,
and
animals.
In
plants
and
soil,
photolytically
induced
isomerization
results
in
a
few
minor
metabolites
not
seen
in
the
rat;
however,
most
of
the
applied
materials
remained
as
parent
compound
as
shown
in
the
apple
and
cucumber
studies.
All
quantitatively
major
plant
and/
or
soil
metabolites
were
also
seen
in
the
rat.
The
toxicity
of
the
major
acid
metabolite,
CGA
 
321113
(
formed
by
hydrolysis
of
the
methyl
ester),
has
been
evaluated
in
cultured
rat
hepatocytes
and
found
to
be
20
times
less
cytologic
than
the
parent
compound.
Additional
toxicity
studies
were
conducted
for
several
minor
metabolites
seen
uniquely
in
plants
and/
or
soil.
The
studies
indicate
that
these
metabolites,
including
CGA
 
357261,
CGA
 
373466,
and
NOA
 
414412,
are
not
mutagenic
to
bacteria
and
are
of
low
acute
toxicity
(
LD50
>
2,000
mg/
kg).
In
conclusion,
the
metabolism
and
toxicity
profiles
support
the
use
of
an
analytical
enforcement
method
that
accounts
for
parent
trifloxystrobin.
8.
Endocrine
disruption.
CGA
 
279202
does
not
belong
to
a
class
of
chemicals
known
for
having
adverse
effects
on
the
endocrine
system.
Developmental
toxicity
studies
in
rats,
rabbits,
and
reproduction
study
in
rats,
gave
no
indication
that
CGA
 
279202
might
have
any
effects
on
endocrine
function
related
to
development
and
reproduction.
The
subchronic
and
chronic
studies
also
showed
no
evidence
of
a
long­
term
effect
related
to
the
endocrine
system.

C.
Aggregate
Exposure
1.
Dietary
exposure.
Assessments
were
conducted
to
evaluate
potential
risks
due
to
chronic
and
acute
dietary
exposure
of
the
U.
S.
population
and
selected
population
subgroups
to
residues
of
trifloxystrobin.
These
analyses
cover
all
registered
crops
plus
the
crops
of
vegetable,
root,
except
sugar
beet,
subgoup1B,
except
radish;
and
the
leafy
petiole
subgroup
4B.
The
dietary
exposure
evaluation
model
((
DEEMTM)
v.
7.76
software)
was
used
to
estimate
the
chronic
and
acute
dietary
exposure.
This
software
uses
the
food
consumption
data
from
the
United
States
Department
of
Agriculture
(
USDA)
Continuing
Surveys
of
Food
Intake
by
Individuals
CSFII
1994
 
1998.
EPA
established
an
acute
population
adjusted
dose
(
aPAD)
of
2.5
milligrams/
kilogram/
day
(
mg/
kg/
day)
for
acute
dietary
risk
assessments
based
on
a
NOAEL
of
250
milligrams/
kilogram
of
body
weight/
day
from
a
rabbit
developmental
toxicity
study
and
an
uncertainty
factor
(
UF)
of
100.
For
chronic
dietary
analyses,
EPA
established
a
chronic
population
adjusted
dose
(
cPAD)
of
0.038
based
on
a
NOAEL
of
3.8
from
a
rat
reproductive
toxicity
study
and
UF
of
100.
Bayer
CropScience
believes
that
results
from
the
acute
and
chronic
dietary
exposure
analyses
described
below
demonstrate
a
reasonable
certainty
that
no
harm
to
the
overall
U.
S.
population
or
any
population
subgroup
will
result
from
the
use
of
trifloxystrobin
on
currently
registered
uses
plus
the
pending
uses
on
vegetable
root
crops,
except
sugar
beets,
subgoup1B,
except
radish;
and
the
leafy
petiole
subgroup
4B.
i.
Food.
Acute
and
chronic
dietary
exposure
assessments
were
performed
using
tolerance
values
for
all
crops
and
assuming
100%
crop
treated.
Acute
exposure,
expressed
at
the
95th
percentile
of
exposure,
was
0.59%
of
the
aPAD
for
females
13
to
50
years
old
(
only
population
subgroup
of
concern).
The
chronic
exposure
was
17.3%
cPAD
for
the
total
U.
S.
population
and
51.5%
cPAD
for
the
most
sensitive
population,
children
1
to
6
years
old.
ii.
Drinking
water.
Using
DEEM
software,
acute
and
chronic
drinking
water
levels
of
concern
(
DWLOC)
were
calculated.
The
acute
DWLOC
was
74,560
and
the
chronic
DWLOC
was
1,100
for
the
total
U.
S.
population
and
184
for
the
most
sensitive
population
subgroup,
children
1
to
6
years
old.
These
values
are
above
the
estimated
concentrations
of
trifloxystrobin
and
its
metabolites
in
drinking
water
as
published
in
the
Federal
Register
of
May
22,
2002,
(
67
FR
35915
 
35924)
(
FRL
 
7178
 
6).
Therefore,
Bayer
CropScience
believe
that
there
is
reasonable
certainty
that
exposure
from
trifloxystrobin
will
not
result
in
harm
to
the
adult
U.
S.
population
or
infants
and
children.
2.
Non­
dietary
exposure.
As
published
in
the
Federal
Register
of
May
22,
2002,
(
67
FR
35915
 
35924)
(
FRL
 
7178
 
6),
EPA
calculated
post
application
exposure
estimates
and
risk
estimates
for
adults
and
children
resulting
from
the
use
of
trifloxystrobin
on
turf
and
recreational
use
sites.
The
margin
of
exposure
(
MOE)
that
resulted
were
above
100
and
all
risks
were
considered
below
EPA's
level
of
concern
(
LOC).

D.
Cumulative
Effects
EPA
has
determined
that
unlike
other
pesticides
for
which
EPA
has
followed
a
cumulative
risk
approach
based
on
a
common
mechanism
of
toxicity,
trifloxystrobin
does
not
appear
to
produce
a
toxic
metabolite
produced
by
other
substances.
Therefore,
EPA
has
not
assumed,
as
published
in
the
Federal
Register
of
May
22,
2002,
(
67
FR
35915
 
35924)
(
FRL
 
7178
 
6),
that
trifloxystrobin
has
a
common
mechanism
of
toxicity
with
other
substances.

E.
Safety
Determination
1.
U.
S.
population.
Based
on
the
information
supplied
under
aggregate
exposure
described
above,
Bayer
CropScience
believe
that
there
is
reasonable
certainty
that
exposure
from
trifloxystrobin
will
not
result
in
harm
to
the
adult
U.
S.
population.
2.
Infants
and
children.
Based
on
the
information
supplied
under
aggregate
exposure
described
above,
Bayer
CropScience
believes
that
there
is
reasonable
certainty
that
exposure
from
trifloxystrobin
will
not
result
in
harm
to
infants
and
children.

F.
International
Tolerances
There
are
no
codex,
Canadian,
or
Mexican
maximum
residue
limits
(
MRLs)
established
for
trifloxystrobin.
[
FR
Doc.
03
 
5193
Filed
3
 
4
 
03;
8:
45
am]

BILLING
CODE
6560
 
50
 
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