Document ID: EPA-HQ-OPP-2003-0166-0001
Agency: epa
Document Type: Notice
Title: Flufenpyr-ethyl; Notice of Filing a Pesticide Petition to Establish a Tolerance for a Certain Pesticide Chemical in or on Food
Posted Date: 2003-06-25T04:00Z

37813
Federal
Register
/
Vol.
68,
No.
122
/
Wednesday,
June
25,
2003
/
Notices
TABLE
1.
 
REGISTRATIONS
WITH
REQUESTS
FOR
AMENDMENTS
TO
DELETE
USES
IN
CERTAIN
PESTICIDE
REGISTRATIONS
 
Continued
Registration
No.
Product
Name
Active
Ingredient
Delete
From
Label
062719
 
00100
Balan
Technical
Benfluralin
Peanuts
068156
 
00001
Technical
Benefin
Benfluralin
Peanuts
Users
of
these
products
who
desire
continued
use
on
crops
or
sites
being
deleted
should
contact
the
applicable
registrant
before
dates
indicated
in
DATES
section
of
this
notice
to
discuss
withdrawal
of
the
application
for
amendment.
This
30
 
day
or
180
 
day
period
will
also
permit
interested
members
of
the
public
to
intercede
with
registrants
prior
to
the
Agency's
approval
of
the
deletion.
Table
2
of
this
unit
includes
the
names
and
addresses
of
record
for
all
registrants
of
the
products
in
Table
1
of
this
unit,
in
ascending
sequence
by
EPA
company
number.

TABLE
2.
 
REGISTRANTS
REQUESTING
VOLUNTARY
CANCELLATION
EPA
Company
No.
Company
Name
and
Address
001270
Zep
Manufacturing
Company
Agent
for:
Zep
Manufacturing
Company,
1310
Seaboard
Industrial
Blvd.,
NW,
Atlanta,
GA
30318
001812
Griffin
L.
L.
C.,
P.
O.
Box
1847,
Valdosta,
GA
31603
002393
Haco
Inc,
P.
O.
Box
7190,
Madison
WI
53707
019713
Drexel
Chemical
Co,
1700
Channel
Avenue,
P.
O.
Box
13327,
Memphis,
TN
38113
040322
Equine
Chemical
Co.
Inc.,
P.
O.
Box
771,
Skiatook,
OK
74070
042750
Pyxis
Regulatory
Consulting
Agent
for:
Albaugh
Inc.,
11324
17th
Avenue
Court
NW,
Gig
Harbor,
WA
98332
062719
Dow
AgroSciences
LLC,
9330
Zionsville
Rd
308/
2E225,
Indianapolis
IN
46268
068156
Dintec
AgriChemicals,
9330
Zionsville
Rd,
Indianapolis,
IN
46268
III.
What
is
the
Agency
Authority
for
Taking
this
Action?

Section
6(
f)(
1)
of
FIFRA
provides
that
a
registrant
of
a
pesticide
product
may
at
any
time
request
that
any
of
its
pesticide
registrations
be
amended
to
delete
one
or
more
uses.
The
Act
further
provides
that,
before
acting
on
the
request,
EPA
must
publish
a
notice
of
receipt
of
any
such
request
in
the
Federal
Register.
Thereafter,
the
Administrator
may
approve
such
a
request.

IV.
Procedures
for
Withdrawal
of
Request
Registrants
who
choose
to
withdraw
a
request
for
use
deletion
must
submit
the
withdrawal
in
writing
to
James
A.
Hollins
using
the
instructions
in
Unit
I.
C.
The
Agency
will
consider
written
withdrawal
requests
postmarked
on
or
before
dates
indicated
in
DATES
section
of
this
notice.

V.
Provisions
for
Disposition
of
Existing
Stocks
The
Agency
has
authorized
the
registrants
to
sell
or
distribute
products
under
the
previously
approved
labeling
for
a
period
of
18
months
after
approval
of
the
revision,
unless
other
restrictions
have
been
imposed,
as
in
Special
Review
actions.

List
of
Subjects
Environmental
protection,
Pesticides
and
pests.

Dated:
June
11,
2003.

Arnold
E.
Layne,

Director,
Information
Resources
and
Services
Division,
Office
of
Pesticide
Programs.

[
FR
Doc.
03
 
16031
Filed
6
 
24
 
03;
8:
45
am]

BILLING
CODE
6560
 
50
 
S
ENVIRONMENTAL
PROTECTION
AGENCY
[
OPP
 
2003
 
0166;
FRL
 
7307
 
8]

Flufenpyr­
ethyl;
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
 
0166,
must
be
received
on
or
before
July
25,
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:
Joanne
I.
Miller,
Registration
Division
(
7505C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460
 
0001;
telephone
number:
(
703)
305
 
6224;
e­
mail
address:
Miller.
Joanne@
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.
Potential
affected
entities
may
include,
but
are
not
limited
to:
 
Crop
production
(
NAICS)
 
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
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/
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68,
No.
122
/
Wednesday,
June
25,
2003
/
Notices
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
 
0166.
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
 
0166.
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
 
0166.
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
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68,
No.
122
/
Wednesday,
June
25,
2003
/
Notices
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
 
0166.
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
 
0166.
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:
June
16,
2003.
Debra
Edwards,
Director,
Registration
Division,
Office
of
Pesticide
Programs.

Summary
of
Petition
The
petitioner
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.

Valent
U.
S.
A.
Corporation
PP
0F6164
EPA
has
received
a
request
from
Valent
U.
S.
A.
Corporation
at
1333
North
California
Boulevard,
Suite
600,
Walnut
Creek,
California
94596
 
8025
pursuant
to
section
408(
d)
of
FFDCA,
21
U.
S.
C.
346a(
d),
to
amend
40
CFR
part
180
to
establish
tolerances
for
residues
of
the
herbicide
chemical
flufenpyr­
ethyl,
ethyl
[
2­
chloro­
4­
fluoro­
5­(
5­
methyl­
6­
oxo­
4­
trifluoromethyl­
1,6­
dihydropyridazin­
1­
yl)
phenoxy]
acetate,
in
or
on
the
raw
agricultural
commodities
corn,
field,
grain;
soybean,
seed;
and
sugarcane,
cane
at
0.01
parts
per
million
(
ppm)
and
for
the
combined
residues
of
the
herbicide
chemical
flufenpyr­
ethyl,
and
its
metabolite,
S­
3153­
acid­
4­
OH,
[
2­
chloro­
4­
hydroxy­
5­
(
5­
methyl­
6­
oxo­
4­
trifluoromethyl­
1,6­
dihydropyridazin­
1­
yl)
phenoxy]
acetic
acid,
free
and
conjugated,
in
or
on
the
raw
agricultural
commodities
corn,
field,
forage
and
corn,
field,
stover
at
0.05
ppm.
EPA
has
determined
that
the
request
contains
data
or
information
consistent
with
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
request.

A.
Residue
Chemistry
Plant
and
animal
metabolism
studies
with
14C­
flufenpyr­
ethyl
have
demonstrated
that
the
residue
of
concern
is
adequately
understood
for
the
purposes
of
these
tolerances.
Practical,
validated
residue
methodology
is
available
to
analyze
all
appropriate
matrices
for
flufenpyr­
ethyl
residues
with
an
LOQ
(
limit
of
quantitation)
of
0.01
ppm,
and
for
S­
3153­
acid­
4­
OH
metabolite
with
an
LOQ
of
0.02
ppm,
adequate
to
enforce
all
proposed
tolerances.
The
potential
for
residues
of
flufenpyr­
ethyl
has
been
evaluated
in
field
corn
grain,
forage,
and
stover;
soybeans;
sugarcane;
feed
items;
in
appropriate
processed
products;
and
animals.
These
studies
are
adequate
to
support
appropriate
tolerances
and
dietary
risk
analyses.
1.
Plant
metabolism.
Metabolism
of
flufenpyr­
ethyl
radiolabeled
with
14C
in
the
phenyl
and
in
the
pyridazinyl
rings
has
been
studied
in
corn
and
soybean
plants
and
in
lactating
goats,
laying
hens,
and
rats.
The
major
metabolic
pathway
in
plants
is
hydrolysis
of
the
ethyl
ester,
followed
by
further
metabolism
into
more
polar
products
by
formation
of
phenolic
glyclones.
At
the
proposed
pre­
harvest
intervals
total
radiocarbon
residue
in
grain
samples
was
very
low
and
adequately
represented
by
parent.
However,
in
plant
material
and
forage
samples,
a
conjugated
carboxylic
acid
phenolic
metabolite
was
present,
the
aglycone
of
which,
S­
3153­
acid­
4­
OH,
was
not
detected
as
an
animal
metabolite.
This
metabolite
was
not
detected
in
any
raw
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Notices
agricultural
commodity
(
RAC)
grain
sample
or
in
sugarcane.
The
residue
of
concern
in
grain
and
sugarcane
is
best
defined
as
the
parent,
flufenpyr­
ethyl.
However,
consistent
with
plant
metabolism
studies,
finite
residues
of
S­
3153­
acid­
4­
OH
were
detected
in
field
corn
forage
and
stover,
and
tolerances
are
proposed.
2.
Ruminant
and
poultry
metabolism.
Metabolism
studies
in
goats
and
hens
demonstrated
that
transfer
of
administered
14C­
flufenpyr­
ethyl
residues
to
tissues
was
low.
Total
14Cresidues
in
goat
milk,
muscle
and
tissues
accounted
for
less
than
1%
of
the
administered
dose.
Total
radiocarbon
residues
(
parent
equivalent)
were
less
than
0.01
ppm
in
all
cases
except
for
approximately
0.15
ppm
in
kidney
and
0.04
ppm
in
liver.
Residues
were
identified
in
excreta
and
all
appropriate
tissues.
In
milk
(
0.002
to
0.008
ppm),
kidney,
and
liver
approximately
70
to
90
percent
of
the
residues
was
identified
as
the
ester
hydrolysis
product,
S­
3153­
acid.
In
poultry,
total
14C
residues
(
parent
equivalent)
in
eggs,
muscle
and
tissues
accounted
for
about
0.1%
of
the
administered
dose,
and
were
less
than
0.01
ppm
in
all
cases
except
for
approximately
0.02
ppm
in
liver.
More
than
half
of
the
liver
residue
was
S­
3153­
acid.
3.
Analytical
method.
Practical
analytical
method
for
detecting
and
measuring
levels
of
flufenpyr­
ethyl
and
validated
in/
on
all
appropriate
agricultural
commodities
and
respective
processing
fractions.
Methodology
that
converts
the
S­
3153­
acid­
4­
O­
glucoside
to
the
corresponding
aglycone,
S­
3153­
acid­
4­
OH,
was
developed
and
validated
with
an
LOQ
of
0.02
ppm.
The
extraction
methodologies
have
been
validated
using
plant
samples
containing
aged
radiochemical
residue
samples
from
14C­
metabolism
studies.
The
methods
have
been
validated
in
soybean
seed,
corn
grain,
and
corn
stover
at
an
independent
laboratory.
The
LOQ
for
flufenpyr­
ethyl
is
0.01
ppm
and
the
LOQ
for
S­
3153­
acid­
4­
OH
is
0.02
ppm
which
will
allow
monitoring
of
food
with
residues
at
the
levels
proposed
for
the
tolerances.
Both
flufenpyr­
ethyl
and
S­
3153­
acid­
4­
OH
have
been
evaluated
using
the
FDA
multiresidue
method
protocol.
4.
Magnitude
of
residues
 
i.
Soybean
seed.
Twenty­
two
field
trials
in
soybeans
were
conducted
in
1997
and
1998
in
15
states
representing
approximately
99%
of
the
soybean
acreage
in
the
U.
S.
(
EPA
Regions
II,
IV,
and
V).
Analysis
of
duplicate
samples
from
these
trials
showed
that
at
the
proposed
maximum
application
rate
(
24.5
grams
active
ingredient
(
a.
i.)/
acre),
or
at
5
times
the
proposed
maximum
application
rate,
there
were
no
measurable
residues
of
flufenpyr­
ethyl
in
soybean
seed
(<
0.005
ppm).
The
analytical
LOQ
was
0.01
ppm.
A
processing
study
in
soybean
seed
treated
at
the
5­
fold
application
rate
demonstrated
that
flufenpyr­
ethyl
was
undetectable
in
all
processed
commodities.
All
these
data
support
a
proposed
tolerance
of
0.01
ppm
for
flufenpyr­
ethyl
in/
on
soybean
seed.
No
additional
tolerances
are
necessary
for
processed
commodities.
ii.
Sugarcane
cane.
Nine
field
trials
in
sugarcane
were
conducted
in
1998
in
4
states
representing
approximately
100%
of
the
sugarcane
acreage
in
the
U.
S.
(
EPA
Regions
II,
IV
and
V).
Analysis
of
duplicate
samples
from
these
trials
showed
that
at
the
proposed
seasonal
maximum
application
rate
(
24.5
grams
a.
i./
acre),
or
at
five
times
the
proposed
maximum
application
rate,
there
were
no
measurable
residues
of
flufenpyrethyl
in
sugarcane
cane
(<
0.005
ppm).
The
analytical
LOQ
was
0.01
ppm.
Because
sugarcane
is
the
vegetative
portion
of
the
plant,
it
is
possible
that
residues
of
the
carboxylic
acid
phenol
metabolite
(
S­
3153­
acid­
4­
OH)
might
be
present.
With
an
LOQ
of
0.02
ppm,
there
was
no
detected
metabolite
in
any
sugarcane
sample.
Samples
of
processed
commodities
from
the
sugarcane
processing
studies
treated
at
5­
fold
were
not
analyzed
because
of
the
absence
of
finite
residues
in
any
of
the
cane
RAC
samples.
All
these
data
support
a
proposed
tolerance
of
0.01
ppm
for
flufenpyr­
ethyl
in/
on
sugarcane
cane.
No
additional
tolerances
are
necessary
for
processed
commodities.
5.
Field
corn.
Twenty­
four
field
trials
in
field
corn
were
conducted
in
1997
(
10)
and
1998
(
14)
in
16
states
representing
approximately
97%
of
the
field
corn
acreage
in
the
U.
S.
(
EPA
Regions
I,
II,
V,
VI,
VII,
VIII,
and
X).
Field
plots
were
treated
at
the
V10
crop
stage.
Forage
was
sampled
32
to
65
days
after
treatment
at
late
R4
to
early
R5
crop
stage.
Grain
and
stover
were
sampled
at
dry
maturity
58
to
115
days
after
application.
i.
Field
corn
grain.
Analysis
of
duplicate
samples
of
grain
from
these
trials
showed
that
at
the
proposed
maximum
application
rate
(
24.5
grams
a.
i./
acre),
at
half
the
proposed
maximum
application
rate
(
12
grams
a.
i./
acre),
or
from
two
field
plots
treated
at
five
times
the
proposed
maximum
application
rate
(
121
grams
a.
i./
acre)
there
were
no
measurable
residues
of
flufenpyr­
ethyl
(<
0.005ppm).
The
analytical
LOQ
was
0.01
ppm.
A
processing
study
in
field
corn
grain
treated
at
the
five
times
the
normal
application
rate
demonstrated
that
flufenpyr­
ethyl
was
undetectable
in
all
processed
commodities.
All
these
data
support
a
proposed
tolerance
of
0.01
ppm
for
flufenpyr­
ethyl
in/
on
field
corn
grain.
No
additional
tolerances
are
necessary
for
processed
commodities.
ii.
Field
corn
forage
and
stover.
Analysis
of
duplicate
samples
of
forage
and
stover
from
these
trials
showed
that
at
the
proposed
maximum
application
rate
(
24.5
grams
a.
i./
acre),
and
at
half
the
proposed
maximum
application
rate
(
12
grams
a.
i./
acre)
there
were
no
measurable
residues
of
flufenpyr­
ethyl
(<
0.005
ppm).
In
forage
and
stover
from
plots
treated
at
5
times
the
proposed
application
rate
(
121
grams
a.
i./
acre)
finite
residue
of
flufenpyr­
ethyl
were
detected
(
0.015
to
0.008
ppm).
Forage
and
stover
samples
were
also
analyzed
for
S­
3153­
acid­
4­
OH.
Finite
residues
of
the
metabolite
were
detected
in
28
of
52
forage
samples,
and
11
of
54
stover
samples
from
plots
treated
at
24.5
grams
a.
i./
acre.
Maximum
residue
values
in
the
two
feed
commodities
were
0.03
ppm.
Forage
and
stover
samples
from
the
two
plots
treated
at
the
5­
fold
rate
showed
maximum
residue
values
of
0.05
ppm.
All
these
data
support
proposed
tolerances
of
0.01
ppm
for
flufenpyr­
ethyl
and
0.04
ppm
S­
3153­
acid­
4­
OH
in/
on
field
corn
forage
and
stover.
6.
Secondary
residues.
Using
proposed
tolerances,
or
for
field
corn
forage
and
stover
the
sum
of
the
tolerances
for
parent
and
metabolite,
to
calculate
the
maximum
feed
exposure
to
fed
animals,
and
using
the
very
low
potential
for
residue
transfer
demonstrated
in
the
lactating
goat
and
laying
hen
metabolism
studies,
detectable
secondary
residues
in
animal
tissues,
milk,
and
eggs
are
not
expected.
Therefore,
tolerances
are
not
proposed
for
these
commodities.
7.
Rotational
crops.
The
results
of
a
confined
rotational
crops
accumulation
study
with
14C­
flufenpyr­
ethyl
indicate
that
no
rotational
crop
planting
restrictions
or
rotational
crop
tolerances
are
required.

B.
Toxicological
Profile
A
full
battery
of
toxicology
testing
including
studies
of
acute,
chronic,
oncogenicity,
developmental,
mutagenicity,
and
reproductive
effects
is
available
for
flufenpyr­
ethyl.
The
acute
toxicity
of
flufenpyr­
ethyl
is
low
by
all
routes.
Subchronic
and
chronic
toxicity
studies
exhibit
no
observable
adverse
effect
level
(
NOAEL)
values
from
a
low
of
40
milligrams/
kilogram/
day
(
mg/
kg/
day)
(
male
mouse
18­
month
oncogenicity)
to
greater
than
1,000
mg/
kg/
day.
Flufenpyr­
ethyl
is
not
oncogenic
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Notices
or
mutagenic,
and
it
is
not
a
reproductive
or
developmental
toxicant
when
tested
in
standard
toxicity
studies.
Animal
metabolism
and
excretion
is
rapid;
there
appear
to
be
no
special
toxicity
concerns
for
a
unique
plant
metabolite;
and
there
is
no
evidence
for
endocrine
effects.
The
kidney
and
liver
appear
to
be
the
target
organs
of
flufenpyr­
ethyl.
EPA
has
not
had
the
opportunity
to
review
the
toxicity
studies
on
flufenpyr­
ethyl
and
has
not
established
toxic
endpoints.
For
chronic
oral
exposure,
Valent
has
chosen
the
NOAEL
from
the
second
rat
reproduction
study
of
100
ppm
(
5
mg/
kg/
day
nominal)
as
the
toxic
endpoint.
There
is
no
study
with
flufenpyr­
ethyl
that
showed
toxicity
that
could
be
associated
with
a
single,
or
acute,
oral
exposure.
Therefore
no
acute
endpoint
could
be
identified,
and
no
acute
oral
risk
analyses
are
performed.
1.
Acute
toxicity.
The
acute
toxicity
of
technical
grade
flufenpyr­
ethyl
is
low
by
all
routes.
Flufenpyr­
ethyl
produces
minimal
toxicity
following
acute
oral,
dermal
or
inhalation
exposures.
The
technical
material
is
essentially
nonirritating
to
the
eye,
is
not
irritating
to
the
skin
and
does
not
cause
dermal
sensitization
in
guinea
pigs.
Flufenpyrethyl
technical
will
be
classified
as
Toxicity
Class
IV.
2.
Genotoxicity.
Flufenpyr­
ethyl
does
not
present
a
genetic
hazard.
Flufenpyrethyl
technical
was
negative
in
the
following
tests
for
mutagenicity:
Ames
assay
with
and
without
S9,
in
vitro
mammalian
cell
gene
mutation
assay
using
L5178Y/
TK /­
mouse
lymphoma
cells,
and
the
in
vivo
mouse
bone
marrow
micronucleus
test.
3.
Reproductive
and
developmental
toxicity.
Developmental
toxicity
studies
have
been
performed
in
rats
and
rabbits,
and
multigenerational
effects
on
reproduction
were
tested
in
rats.
i.
Rats.
In
the
developmental
toxicity
study
conducted
with
rats,
technical
flufenpyr­
ethyl
was
administered
by
gavage
at
levels
of
0,
100,
300,
and
1,000
mg/
kg/
day
during
gestation
days
6
through
19.
There
were
no
adverse
maternal
or
fetal
effects
observed.
The
NOAEL
for
both
maternal
and
developmental
toxicity
was
found
to
be
1,000
mg/
kg/
day,
the
highest
dose
tested.
ii.
Rabbits.
Flufenpyr­
ethyl
technical
was
tested
in
a
developmental
toxicity
study
in
rabbits
at
doses
of
0,
100,
300
and
1,000
mg/
kg/
day
during
gestation
days
6
through
28.
Maternal
mortality
occurred
at
the
two
highest
doses
tested
but
the
deaths
at
300
ppm
were
not
considered
to
be
the
result
of
systemic
toxicity.
In
surviving
animals
and
their
fetuses,
there
were
no
adverse
effects.
Based
on
these
results,
the
maternal
toxicity
NOAEL
was
300
mg/
kg/
day
and
the
developmental
toxicity
NOAEL
was
1,000
mg/
kg/
day.
A
second
developmental
toxicity
study
was
conducted
to
confirm
the
maternal
NOAEL
at
dose
levels
of
0,
100,
200,
300
or
1,000
mg/
kg/
day
during
gestation.
Again,
maternal
mortality
occurred,
but
at
all
dose
levels.
Detailed
examination
of
these
animals
showed
in
the
majority
of
cases
the
cause
of
death
to
be
test
material
aspiration
into
the
lungs.
The
cause
of
death
for
several
animals
at
the
high
dose
could
not
be
determined.
Their
deaths
were
therefore
attributed
to
systemic
toxicity.
There
were
no
other
adverse
effects
in
the
surviving
dams
or
fetuses.
The
NOAEL
for
this
study
(
and
overall
for
both
rabbit
developmental
toxicity
studies)
were
found
to
be
300
mg/
kg/
day
(
maternal)
and
1,000
mg/
kg/
day
(
developmental).
iii.
Reproduction.
In
the
rat
reproduction
study,
flufenpyr­
ethyl
technical
was
administered
in
the
diet
at
levels
of
0,
200,
2,000,
and
20,000
ppm
for
2
 
generations.
Parental
toxicity
was
observed
at
all
dose
levels,
although
the
effects
at
the
low
dose
were
minimal.
Parental
toxicity
was
exhibited
by
dose­
related
microscopic
changes
in
the
kidney
in
high
dose
F0
animals,
in
all
treated
F1
males,
and
in
high
dose
F1
females.
There
were
also
2
high
dose
F1
males
that
died
possibly
as
a
result
of
treatment.
Midzonal
cytoplasmic
vacuolation
of
the
hepatocytes
was
also
observed
in
the
liver
of
all
groups
of
treated
animals
in
both
generations.
Based
on
the
results
of
this
study,
the
NOAEL
for
parental
toxicity
was
considered
to
be
less
than
200
ppm.
The
NOAEL
for
reproductive
and
neonatal
toxicity
was
considered
to
be
20,000
ppm.
A
second
1
 
generation
reproduction
study
was
performed
to
establish
a
clear
NOAEL
for
adult
kidney
lesions
using
the
dose
levels
of
20,
50
and
100
ppm.
The
results
of
the
study
indicate
that
the
NOAEL
for
histological
changes
in
the
kidneys
of
F1
male
rats
was
100
ppm.
No
other
treatment
related
findings
were
noted
at
any
dose
level
indicating
100
ppm
as
the
NOAEL
for
treatment
and
reproductive
effects
evaluated
in
the
study.
A
mechanistic
study
was
also
conducted
to
investigate
the
reproducibility
and
reversibility
of
the
kidney
lesions
observed
in
the
initial
2­
generation
reproduction
study.
In
the
first
study,
the
effects
observed
at
200
ppm
in
the
F1
males,
basophilic
tubules
and
interstitial
inflamation,
were
minimal
but
slightly
increased
in
incidence
and
severity
and
a
slight
increase
in
interstitial
fibrosis
of
the
cortex
was
also
observed.
In
this
mechanistic
study,
using
dose
levels
of
0
and
2,000
ppm,
the
NOAEL
for
histological
changes
in
the
kidneys
of
F0
and
F1
male
rats
and
reproductive
effects
was
2,000
ppm.
The
histological
changes
seen
in
the
kidneys
in
the
original
study
was
not
reproducible.
4.
Subchronic
toxicity.
Subchronic
oral
toxicity
studies
conducted
with
flufenpyr­
ethyl
in
the
rat,
mouse
and
dog
indicate
a
low
level
of
toxicity.
i.
Rats.
Pure
(
99.4%)
flufenpyr­
ethyl
was
tested
in
rats
at
dose
levels
of
0,
600,
2,000,
6,000,
and
20,000
ppm
in
the
diet
for
13
weeks.
Effects
observed
included
urinary
incontinence,
increased
food
and
water
consumption,
slight
hematological
and
blood
biochemistry
changes,
decreased
spleen
weights,
an
increase
in
the
incidence
and
severity
of
basophilic
tubules
of
the
kidneys
and
slight
to
mild
diffusely
distributed
vacuolation
in
the
liver.
Based
on
these
results,
the
NOAEL
was
2,000
ppm
(
134.2
mg/
kg/
day)
for
the
males
and
20,000
ppm
(
1,509.6
mg/
kg/
day)
for
the
females.
In
an
additional
study,
flufenpyr­
ethyl
technical
was
tested
in
rats
at
dose
levels
of
0,
1,000,
10,000,
and
20,000
ppm
in
the
diet
for
13
weeks.
Effects
observed
included
urinary
incontinence,
increased
food
and
water
consumption,
and
mild
urinalysis,
hematological
and
blood
biochemistry
changes.
Thymus
weights
were
slightly
increased.
Diffusely
distributed
hepatic
vacuolation
was
seen
in
the
high
dose
males.
Based
on
these
findings,
the
NOAEL
was
10,000
ppm
(
595.2
mg/
kg/
day)
in
the
males
and
20,000
ppm
(
1,377.5
mg/
kg/
day)
in
the
females.
ii.
Mice.
In
a
4
 
week
study,
CD­
1
mice
were
fed
pure
flufenpyr­
ethyl
at
dose
levels
of
0,
300,
1,000,
3,000,
and
7,000
ppm.
Effects
were
slight
anemia,
changes
in
blood
biochemistry,
increased
liver
and
thymus
weights,
and
enlarged
liver.
Centrilobular
hepatocellular
hypertrophy
and
vacuolation
and
increases
in
the
severity
and
incidence
of
hepatic
focal
and
single
cell
necrosis
were
observed.
Based
on
these
findings,
the
NOAEL
was
300
ppm
(
44.9
mg/
kg/
day)
for
males
and
1,000
(
210.5
mg/
kg/
day)
for
females.
In
a
13­
week
study,
flufenpyrethyl
technical
was
administered
to
mice
at
dose
levels
of
0,
300,
1,000,
3,000,
and
7,000
ppm.
Slight
anemia
and
blood
biochemistry
changes
were
noted.
Liver
weights
were
increased
and
ovary
weights
were
decreased.
Histopathological
findings
included:
Hepatocellular
fatty
vacuolation.
The
NOAEL
for
this
study
in
both
sexes
was
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Notices
1,000
ppm
(
128.4
mg/
kg/
day
for
males
and
155.7
mg/
kg/
day
for
females).
iii.
Dogs.
Flufenpyr­
ethyl
technical
was
administered
for
13
weeks
via
capsule
to
Beagle
dogs
at
levels
of
0,
100,
300
or
1,000
mg/
kg/
day.
The
effects
were
very
minimal.
Only
small
nonsignificant
decreases
in
body
weight
and
slightly
elevated
alkaline
phosphatase
values
were
noted.
In
the
absence
of
other
effects,
the
NOAEL
in
both
sexes
was
determined
to
be
1,000
mg/
kg/
day.
iv.
Dermal.
A
21
 
day
dermal
toxicity
study
in
rats
with
flufenpyr­
ethyl
technical
did
not
produce
any
signs
of
dermal
or
systemic
toxicity
at
1,000
mg/
kg/
day,
the
highest
dose
tested.
5.
Chronic
toxicity.
Flufenpyr­
ethyl
technical
has
been
tested
in
chronic
studies
with
dogs,
rats
and
mice.
i.
Rats.
In
a
104
 
week
combined
chronic/
oncogenicity
study
in
rats,
flufenpyr­
ethyl
technical
was
administered
at
dose
levels
of
0,
100,
1,000,
10,000,
or
20,000
ppm
in
the
diet
for
24
months.
Urinary
incontinence,
increased
food
and
water
consumption,
changes
in
urinalysis,
hematological
and
blood
biochemistry
changes
were
observed
but
the
effects
were
not
toxicologically
significant.
No
neoplastic
lesions
were
observed.
The
NOAEL
was
found
to
be
20,000
ppm
(
777.5
mg/
kg/
day
for
males
and
1024
mg/
kg/
day
for
females).
ii.
Mice.
In
a
78
 
week
oncogenicity
study
with
mice,
flufenpyr­
ethyl
technical
was
administered
at
dose
levels
of
0,
350,
3,500,
and
7,000
ppm.
Male
animals
exhibited
slight
anemia.
Females
had
increased
liver
and
kidney
weights
(
week
53
only).
Slight
to
moderate
hepatocellular
fatty
vacuolation
and
necrosis
were
observed.
There
were
no
increases
in
incidence
of
pre­
neoplastic
or
neoplastic
lesions.
Based
on
these
results,
the
NOAEL
was
350
ppm
for
both
sexes
(
39.9
mg/
kg/
day
for
males
and
43.7
mg/
kg/
day
for
females).
iii.
Dogs.
In
a
52
 
week
chronic
study,
flufenpyr­
ethyl
technical
was
administered
by
capsule
to
Beagle
dogs
at
dose
levels
of
0,
50,
200,
and
1,000
mg/
kg/
day.
There
were
very
few
observations
related
to
treatment.
Slightly
elevated
alkaline
phosphatase
values
were
again
observed,
but
they
were
not
accompanied
with
any
other
findings
and
were
thus
considered
not
to
be
an
adverse
effect.
The
NOAEL
was
determined
to
be
1,000
mg/
kg/
day,
the
highest
dose
tested.
iv.
Carcinogenicity.
Flufenpyr­
ethyl
is
not
a
carcinogen.
Studies
with
flufenpyr­
ethyl
technical
have
shown
that
repeated
high
dose
exposures
produced
minimal
signs
of
toxicity,
including
slight
hematologic,
liver
and
kidney
effects,
but
did
not
produce
cancer
in
test
animals.
No
oncogenic
response
was
observed
in
a
rat
2
 
year
chronic
feeding/
oncogenicity
study
or
in
a
78­
week
study
on
mice.
Valent
anticipates
that
the
oncogenicity
classification
of
flufenpyr­
ethyl
will
be
``
E''
(
no
evidence
of
carcinogenicity
for
humans).
6.
Animal
metabolism.
Following
oral
administration
of
14C­
phenyl­
labeled
flufenpyr­
ethyl
to
rats
at
50
mg/
kg,
the
majority
of
the
radiocarbon
is
eliminated
from
the
body
within
2
days.
Approximately
half
is
excreted
in
the
urine
and
the
balance
is
excreted
in
the
feces.
Tissue
residues
are
very
low
7
days
after
administration
(<
0.09%
of
the
administered
dose).
The
major
metabolite
was
identified
as
[
2­
chloro­
4­
fluoro­
5­(
5­
methyl­
6­
oxo­
4­
trfluoromethyl
1,6­
dihydropyridazin­
1­
yl)
phenoxy]
acetic
acid
(
S­
3153­
acid)
which
accounted
for
93.2%
of
the
dose.
Two
other
minor
metabolites
each
accounted
for
less
than
5%
of
the
administered
radiocarbon.
Flufenpyrethyl
was
detected
only
in
feces
(
0.5%).
The
major
reaction
was
cleavage
of
the
ester
linkage;
minor
reactions
were
hydroxylation
of
the
5­
methyl
of
pyridazine
ring
and
cleavage
of
the
ether
linkage
between
the
phenyl
group
and
the
carboxymethyl
group.
7.
Metabolite
toxicity.
Metabolism
studies
of
flufenpyr­
ethyl
in
rats,
goats
and
hens,
as
well
as
the
fish
bioaccumulation
study
demonstrate
that
the
parent
is
very
rapidly
metabolized
and
eliminated.
Because
parent
and
metabolites
are
not
retained
in
the
body,
the
potential
for
acute
toxicity
from
in
situ
formed
metabolites
is
low.
The
potential
for
chronic
toxicity
is
adequately
tested
by
chronic
exposure
to
the
parent
at
the
maximum
tolerated
dose
(
MTD)
and
consequent
chronic
exposure
to
the
internally
formed
metabolites.
One
plant
metabolite,
S­
3153­
acid­
4­
OH
was
not
detected
as
an
animal
metabolite.
This
compound
was
tested
for
acute
oral
toxicity
in
rats,
and
for
mutagenicity
Ames
testing
with
and
without
mixed
function
oxidation
(
S9
mix).
The
metabolite
caused
no
mortality
in
rats
at
5,000
mg/
kg
the
highest
dose
tested,
and
was
not
mutagenic
at
up
to
5,000
micrograms
per
plate.
8.
Potential
endocrine
effects.
No
special
studies
to
investigate
the
potential
for
estrogenic
or
other
endocrine
effects
of
flufenpyr­
ethyl
have
been
performed.
However,
as
summarized
above,
a
large
and
detailed
toxicology
data
base
exists
for
the
compound
including
studies
in
all
required
categories.
These
studies
include
acute,
sub­
chronic,
chronic,
developmental,
and
reproductive
toxicology
studies
including
detailed
histology
and
histopathology
of
numerous
tissues,
including
endocrine
organs,
following
repeated
or
long­
term
exposures.
These
studies
are
considered
capable
of
revealing
endocrine
effects.
The
results
of
all
of
these
studies
show
no
evidence
of
any
endocrine­
mediated
effects
and
no
pathology
of
the
endocrine
organs.
Consequently,
it
is
concluded
that
flufenpyr­
ethyl
does
not
possess
estrogenic
or
endocrine
disrupting
properties.

C.
Aggregate
Exposure
1.
Dietary
exposure.
A
full
battery
of
toxicology
testing
including
studies
of
acute,
chronic,
oncogenicity,
developmental,
mutagenicity,
and
reproductive
effects
is
available
for
flufenpyr­
ethyl.
EPA
has
not
had
the
opportunity
to
review
the
toxicity
studies
on
flufenpyr­
ethyl
and
has
not
established
toxic
endpoints
of
concern
for
use
in
risk
analyses.
For
chronic
oral
exposure,
Valent
has
chosen
the
NOAEL
from
the
second
rat
reproduction
study
of
100
ppm
(
5
mg/
kg/
day
nominal)
as
the
toxic
endpoint.
There
is
no
study
with
flufenpyr­
ethyl
that
showed
toxicity
that
could
be
associated
with
a
single,
or
acute,
oral
exposure.
Therefore
no
acute
endpoint
could
be
identified,
and
no
acute
oral
risk
analyses
are
performed.
The
chronic
RfD
using
the
standard
100­
fold
uncertainty
factor
is
0.05
mg/
kg/
day,
and
because
there
is
no
evidence
of
enhances
susceptibility
of
infants
and
children,
the
FQPA
extra
10­
fold
uncertainty
factor
is
removed.
Thus,
the
Population
Adjusted
Dose
for
chronic
oral
exposure
(
cPAD)
used
in
these
risk
assessments
is
0.05
mg/
kg/
day.
i.
Food
 
a.
Acute
dietary
exposure.
There
is
no
acute
oral
toxic
endpoint
identified,
and
so
no
acute
exposure
and
risk
analysis
was
performed.
b.
Chronic
dietary
exposures
to
flufenpyr­
ethyl
residues
were
calculated
for
the
U.
S.
population
and
25
population
subgroups.
This
Tier
I
analysis
includes
residue
contribution
from
the
field
corn,
soybean
and
sugarcane
uses
and
assumes
tolerancelevel
residues
and
100%
of
the
crops
treated.
The
results
from
several
representative
subgroups
are
listed
below.
For
all
population
subgroups,
chronic
dietary
exposure
was
below
0.2%
of
the
cPAD.
Generally,
the
Agency
has
no
cause
for
concern
if
total
chronic
exposure
to
residues
contributed
by
published
and
proposed
tolerances
is
less
than
100%
of
the
cPAD.

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Notices
TIER
I
 
CALCULATED
CHRONIC
DIETARY
EXPOSURES
TO
THE
TOTAL
U.
S.
POPULATION
AND
SELECTED
SUBPOPULATIONS
TO
FLUFENPYR­
ETHYL
RESIDUES
IN
FOOD
(
CPAD
=
0.05
MG/
KG/
DAY)

Population
Subgroup
Exposure
(
mg/
kg/
day)
Percent
of
cPAD
Total
U.
S.
population
0.000025
0.05
Males
(
13
­
19
years)
0.000032
0.06
Females
(
13
+
(
nursing))
0.000019
0.04
Females
(
13
+
(
pregnant/
not
nursing))
0.000021
0.04
Children
(
7
­
12
years)
0.000043
0.09
Children
(
1
­
6
years)
0.000056
0.11
All
infants
(<
1
year)
0.000067
0.13
Non­
nursing
infants
0.000082
0.16
Nursing
infants
0.000017
0.03
ii.
Drinking
water.
Since
flufenpyrethyl
is
applied
outdoors
to
growing
agricultural
crops
and
can
be
applied
by
aircraft,
the
potential
exists
for
the
parent
or
its
metabolites
to
reach
ground
water
or
surface
water
that
may
be
used
for
drinking
water.
Because
of
the
physical
and
environmental
fate
properties
of
flufenpyr­
ethyl,
it
is
unlikely
that
flufenpyr­
ethyl
or
its
metabolites
can
leach
to
potable
ground
water.
To
quantify
potential
exposure
from
drinking
water,
surface
water
concentrations
for
flufenpyr­
ethyl
were
estimated
using
Generic
Expected
Enviornmental
Concentration
(
GENEEC
1.2.).
The
56
 
day
average
GENEEC
concentration
was
0.027
ppb.
Using
standard
assumptions
about
body
weight
and
water
consumption,
the
maximum
chronic
exposure
from
this
drinking
water
would
be
0.000000763
and
0.00000267
mg/
kg/
day
for
adults
and
children,
respectively;
0.0053
percent
of
the
cPAD
of
0.05
mg/
kg/
day
for
children.
The
contribution
of
drinking
water
to
chronic
dietary
exposures
is
much
smaller
than
that
from
food,
and
adds
negligible
risk.
2.
Non­
dietary
exposure.
Flufenpyrethyl
is
proposed
only
for
agricultural
uses
and
no
homeowner,
turf,
or
industrial
uses.
Thus,
no
non­
dietary
risk
assessment
is
needed.

D.
Cumulative
Effects
Section
408(
b)(
2)(
D)(
v)
requires
that
the
Agency
must
consider
``
available
information''
concerning
the
cumulative
effects
of
a
particular
pesticide's
residues
and
``
other
substances
that
have
a
common
mechanism
of
toxicity.''
Available
information
in
this
context
include
not
only
toxicity,
chemistry,
and
exposure
data,
but
also
scientific
policies
and
methodologies
for
understanding
common
mechanisms
of
toxicity
and
conducting
cumulative
risk
assessments.
For
most
pesticides,
although
the
Agency
has
some
information
in
its
files
that
may
turn
out
to
be
helpful
in
eventually
determining
whether
a
pesticide
shares
a
common
mechanism
of
toxicity
with
any
other
substances,
EPA
does
not
at
this
time
have
the
methodologies
to
resolve
the
complex
scientific
issues
concerning
common
mechanism
of
toxicity
in
a
meaningful
way.
There
are
other
pesticidal
compounds
that
are
structurally
related
to
flufenpyrethyl
and
may
have
similar
effects
on
animals.
In
consideration
of
potential
cumulative
effects
of
flufenpyr­
ethyl
and
other
substances
that
may
have
a
common
mechanism
of
toxicity,
there
are
currently
no
available
data
or
other
reliable
information
indicating
that
any
toxic
effects
produced
by
flufenpyrethyl
would
be
cumulative
with
those
of
other
chemical
compounds.
Thus,
only
the
potential
risks
of
flufenpyr­
ethyl
have
been
considered
in
this
assessment
of
aggregate
exposure
and
effects.
Valent
will
submit
information
for
EPA
to
consider
concerning
potential
cumulative
effects
of
flufenpyr­
ethyl
consistent
with
the
schedule
established
by
EPA
in
the
Federal
Register
of
August
4,
1997
(
62
FR
42020)
(
FRL
 
5734
 
6)
and
other
subsequent
EPA
publications
pursuant
to
the
Food
Quality
Protection
Act
of
1996
(
FQPA).

E.
Safety
Determination
The
FQPA
introduced
a
new
standard
of
safety,
a
reasonable
certainty
of
no
harm.
To
make
this
determination,
at
this
time
the
Agency
should
consider
only
the
incremental
risk
of
flufenpyrethyl
in
its
exposure
assessment.
Since
the
potential
chronic
and
acute
exposures
to
flufenpyr­
ethyl
are
small
(<
100%
of
cPAD
and
aPAD)
the
provisions
of
the
FQPA
will
not
be
violated.
1.
U.
S.
population
 
i.
Acute
risk.
There
is
no
acute
oral
toxic
endpoint
available,
so
no
risk
analysis
was
performed.
ii.
Chronic
risk.
Using
the
dietary
exposure
assessment
procedures
described
above
for
flufenpyr­
ethyl,
calculated
chronic
dietary
exposure
resulting
from
residue
exposure
from
proposed
uses
of
flufenpyr­
ethyl
is
minimal.
The
estimated
chronic
dietary
exposure
from
food
for
the
overall
U.
S.
population
and
many
non­
child/
infant
subgroups
is
0.064
to
0.042%
of
the
cPAD.
Addition
of
the
small
but
worse
case
potential
exposure
from
drinking
water
(
calculated
above)
increases
exposure
by
only
0.000000763
mg/
kg/
day
(
0.0053%
of
cPAD)
and
the
maximum
occupancy
of
the
cPAD
from
0.064%
to
0.066%.
Generally,
the
Agency
has
no
cause
for
concern
if
total
residue
contribution
is
less
than
100%
of
the
cPAD.
It
can
be
concluded
that
there
is
a
reasonable
certainty
that
no
harm
will
result
to
the
overall
U.
S.
population
and
many
non­
child/
infant
subgroups
from
aggregate,
chronic
exposure
to
flufenpyr­
ethyl
residues.
2.
Safety
factor
for
infants
and
children.
In
assessing
the
potential
for
additional
sensitivity
of
infants
and
children
to
residues
of
flufenpyr­
ethyl,
FFDCA
section
408
provides
that
EPA
shall
apply
an
additional
margin
of
safety,
up
to
10­
fold,
for
added
protection
for
infants
and
children
in
the
case
of
threshold
effects
unless
EPA
determines
that
a
different
margin
of
safety
will
be
safe
for
infants
and
children.

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/
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25,
2003
/
Notices
In
assessing
the
potential
for
additional
sensitivity
of
infants
and
children
to
residues
of
flufenpyr­
ethyl,
EPA
considers
the
completeness
of
the
human
health
effects
data,
particularly
those
studies
that
evaluate
toxicity
to
reproduction
and
to
fetal
and
developing
young
experimental
animals.
These
studies
include
developmental
toxicity
studies
in
the
rat
and
rabbit
and
a
2
 
generation
reproduction
study
in
the
rat.
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
prenatal
and
postnatal
effects
from
exposure
to
the
pesticide,
information
on
the
reproductive
capability
of
both
male
and
female
mating
animals
and
data
on
systemic
toxicity.
3.
Developmental
toxicity.
Flufenpyrethyl
is
not
a
developmental
toxicant
in
either
rats
or
rabbits.
In
the
developmental
toxicity
study
conducted
with
rats,
the
NOAEL
for
both
maternal
and
developmental
toxicity
was
found
to
be
1,000
mg/
kg/
day,
the
highest
dose
tested.
Flufenpyr
technical
was
tested
in
two
developmental
toxicity
studies
in
rabbits
because
of
unexpected
maternal
mortality.
In
the
first
study
maternal
mortality
occurred
at
the
two
highest
doses
tested.
In
surviving
animals
and
their
fetuses,
there
were
no
adverse
effects.
Based
on
these
results,
the
maternal
toxicity
NOAEL
was
100
mg/
kg/
day
and
the
developmental
toxicity
NOAEL
was
1,000
mg/
kg/
day.
In
the
second
study
maternal
mortality
again
occurred,
but
at
all
dose
levels.
Detailed
examination
of
most
these
animals
showed
the
cause
of
death
to
be
test
material
aspiration
into
the
lungs.
There
were
no
other
adverse
effects
in
the
surviving
dams
or
fetuses.
The
NOAEL
for
this
study
and
the
overall
NOAEL
for
rabbits
was
found
to
be
300
mg/
kg/
day
(
maternal)
and
1,000
mg/
kg/
day
(
developmental).
4.
Reproduction.
In
the
rat
reproduction
study,
flufenpyr­
ethyl
technical
was
administered
for
2
 
generations.
Parental
toxicity
(
kidney
and
liver
effects)
was
observed
at
all
dose
levels,
although
the
effects
at
the
low
dose
were
minimal.
There
were
no
effects
at
any
dose
on
any
reproductive
parameter.
Based
on
the
results
of
this
study,
the
NOAEL
for
parental
toxicity
was
considered
to
be
less
than
200
ppm.
The
NOAEL
for
reproductive
and
neonatal
toxicity
was
considered
to
be
20,000
ppm.
A
second
1
 
generation
reproduction
study
was
performed
to
establish
a
clear
NOAEL
for
adult
kidney
lesions
using
the
dose
levels
of
20,
50
and
100
ppm.
The
results
of
the
study
indicate
that
the
NOAEL
for
histological
changes
in
the
kidneys
for
F1
male
rats
was
100
ppm.
No
other
treatment­
related
findings
were
noted
at
any
dose
level
indicating
100
ppm
as
the
NOAEL
for
treatment
and
reproductive
effects
evaluated
in
the
study.
A
mechanistic
study
was
also
conducted
to
investigate
the
reproducibility
and
reversibility
of
the
kidney
lesions
observed
in
the
initial
2
 
generation
reproduction
study.
In
the
first
study,
the
effects
observed
at
200
ppm
in
the
F1
males,
basophilic
tubules
and
interstitial
inflamation,
were
minimal
but
slightly
increased
in
incidence
and
severity
and
a
slight
increase
in
interstitial
fibrosis
of
the
cortex
was
also
observed.
In
this
mechanistic
study,
using
dose
levels
of
0
and
2,000
ppm,
the
NOAEL
for
histological
changes
in
the
kidneys
of
F0
and
F1
male
rats
and
reproductive
effects
was
2,000
ppm.
The
histological
changes
seen
in
the
kidneys
in
the
original
study
was
not
reproducible.
The
toxicological
data
base
for
evaluating
prenatal
and
postnatal
toxicity
for
flufenpyr­
ethyl
is
complete
with
respect
to
current
data
requirements.
Valent
concludes
that
there
is
no
evidence
that
fetal,
or
developing
young
experimental
animals
are
any
more
susceptible
to
the
effects
of
flufenpyr­
ethyl
than
adult
animals.
Therefore
there
is
no
need
for
an
extra
FQPA
uncertainly
factor
to
be
further
protective
of
infants
and
children.
5.
Acute
exposure
and
risk.
There
is
no
acute
oral
toxic
endpoint
available,
so
no
risk
analysis
was
performed.
6.
Chronic
exposure
and
risk.
Using
the
conservative
exposure
assumptions
described
above,
the
percentage
of
the
cPAD
that
will
be
utilized
by
dietary
(
food
only)
exposure
to
residues
of
flufenpyr­
ethyl
ranges
from
0.16%
for
non­
nursing
infants,
to
0.03%
for
nursing
infants.
Adding
the
worse
case
potential
incremental
exposure
to
infants
and
children
from
flufenpyrethyl
in
drinking
water
(
0.00000267
mg/
kg/
day)
increases
the
aggregate,
chronic
dietary
exposure
by
0.0053%
The
addition
of
the
exposure
attributable
to
drinking
water
increases
the
occupancy
of
the
cPAD
for
Non­
Nursing
Infants
from
0.164
to
0.169
percent.
EPA
generally
has
no
concern
for
exposures
below
100%
of
the
cPAD
because
the
cPAD
represents
the
level
at
or
below
which
daily
aggregate
dietary
exposure
over
a
lifetime
will
not
pose
appreciable
risks
to
human
health.
It
can
be
concluded
that
there
is
a
reasonable
certainty
that
no
harm
will
result
to
infants
and
children
from
aggregate,
chronic
exposure
to
flufenpyr­
ethyl
residues.
7.
Safety
determination
summary.
Aggregate
chronic
dietary
exposure
to
various
sub­
populations
of
children
and
adults
demonstrate
acceptable
risk.
Chronic
dietary
exposures
to
flufenpyrethyl
occupy
considerably
less
than
100%
of
the
cPAD.
Acute
dietary
risk
to
children
from
flufenpyr­
ethyl
should
not
be
of
concern.
Further,
flufenpyrethyl
has
only
agricultural
uses
and
no
other
uses,
such
as
indoor
pest
control,
homeowner
or
turf,
that
could
lead
to
unique,
enhanced
exposures
to
vulnerable
sub­
groups
of
the
population.
It
can
be
concluded
that
there
is
a
reasonable
certainty
that
no
harm
will
result
to
the
U.
S.
population
or
to
any
sub­
group
of
the
U.
S.
population,
including
infants
and
children,
from
aggregate
chronic
exposures
to
flufenpyr­
ethyl
residues
resulting
from
proposed
uses.
There
is
no
evidence
that
acute
oral
exposures
to
flufenpyr
ethyl
causes
appreciable
toxicity,
and
no
exposure
and
risk
analyses
are
appropriate.

F.
International
Tolerances
There
are
no
existing
U.
S.
tolerances
or
Codex
Maximum
Residue
Limits
for
flufenpyr­
ethyl.
[
FR
Doc.
03
 
16033
Filed
6
 
24
 
03;
8:
45
am]

BILLING
CODE
6560
 
50
 
S
ENVIRONMENTAL
PROTECTION
AGENCY
[
OPPT
 
2003
 
0031;
FRL
 
7315
 
1]

Certain
New
Chemicals;
Receipt
and
Status
Information
AGENCY:
Environmental
Protection
Agency
(
EPA).
ACTION:
Notice.

SUMMARY:
Section
5
of
the
Toxic
Substances
Control
Act
(
TSCA)
requires
any
person
who
intends
to
manufacture
(
defined
by
statute
to
include
import)
a
new
chemical
(
i.
e.,
a
chemical
not
on
the
TSCA
Inventory)
to
notify
EPA
and
comply
with
the
statutory
provisions
pertaining
to
the
manufacture
of
new
chemicals.
Under
sections
5(
d)(
2)
and
5(
d)(
3)
of
TSCA,
EPA
is
required
to
publish
a
notice
of
receipt
of
a
premanufacture
notice
(
PMN)
or
an
application
for
a
test
marketing
exemption
(
TME),
and
to
publish
periodic
status
reports
on
the
chemicals
under
review
and
the
receipt
of
notices
of
commencement
to
manufacture
those
chemicals.
This
status
report,
which
covers
the
period
from
May
26,
2003
to
June
2,
2003,
consists
of
the
PMNs
and
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