Document ID: EPA-HQ-OPP-2003-0147-0001
Agency: epa
Document Type: Rule
Title: Bacillus thuringiensis Cry1F Protein in Cotton; Temporary Exemption from the Requirement of a Tolerance
Posted Date: 2003-04-30T04:00Z

23073
Federal
Register
/
Vol.
68,
No.
83
/
Wednesday,
April
30,
2003
/
Rules
and
Regulations
[
FR
Doc.
03
 
10262
Filed
4
 
29
 
03;
8:
45
a.
m.]

BILLING
CODE
6560
 
50
 
S
ENVIRONMENTAL
PROTECTION
AGENCY
40
CFR
Part
180
[
OPP
 
2003
 
0147;
FRL
 
7302
 
4]

Bacillus
thuringiensis
Cry1F
Protein
in
Cotton;
Temporary
Exemption
from
the
Requirement
of
a
Tolerance
AGENCY:
Environmental
Protection
Agency
(
EPA).
ACTION:
Final
rule.

SUMMARY:
This
regulation
establishes
a
temporary
exemption
from
the
requirement
of
a
tolerance
for
residues
of
the
Bacillus
thuringiensis
Cry1F
protein
in
cotton
when
applied/
used
as
a
plant­
incorporated
protectant.
Mycogen
Seeds,
c/
o
Dow
AgroSciences
LLC,
submitted
a
petition
to
EPA
under
the
Federal
Food,
Drug,
and
Cosmetic
Act
(
FFDCA),
as
amended
by
the
Food
Quality
Protection
Act
of
1996
(
FQPA),
requesting
the
temporary/
tolerance
exemption.
This
regulation
eliminates
the
need
to
establish
a
maximum
permissible
level
for
residues
of
Bacillus
thuringiensis
Cry1F
protein
in
cotton.
The
temporary
tolerance
exemption
will
expire
on
May
1,
2004.
DATES:
This
regulation
is
effective
April
30,
2003.
Objections
and
requests
for
hearings,
identified
by
docket
ID
number
OPP
 
2003
 
0147,
must
be
received
by
EPA
on
or
before
June
30,
2003.
ADDRESSES:
Written
objections
and
hearing
requests
may
be
submitted
electronically,
by
mail,
or
through
hand
delivery/
courier.
Follow
the
detailed
instructions
as
provided
in
Unit
VIII.
of
the
SUPPLEMENTARY
INFORMATION.
FOR
FURTHER
INFORMATION
CONTACT:
Leonard
Cole,
Biopesticides
and
Pollution
Prevention
Division
(
7511C),
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460
 
0001;
telephone
number:
(
703)
305
 
5412;
e­
mail
address:
cole.
leonard@
epa.
gov.

SUPPLEMENTARY
INFORMATION:

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

You
may
be
affected
by
this
action
if
you
are
an
agricultural
producer,
food
manufacturer,
or
pesticide
manufacturer.
Potentially
affected
categories
and
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
 
0147.
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/.
A
frequently
updated
electronic
version
of
40
CFR
part
180
is
available
at
http://
www.
access.
gpo.
gov/
nara/
cfr/
cfrhtml
_
00/
Title
_
40/
40cfr180
_
00.
html,
a
beta
site
currently
under
development.
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.

II.
Background
and
Statutory
Findings
In
the
Federal
Register
of
October
9,
2002
(
67
FR
62971)
(
FRL
 
7196
 
2),
EPA
issued
a
notice
pursuant
to
section
408
of
the
FFDCA,
21
U.
S.
C.
346a,
as
amended
by
FQPA
(
Public
Law
104
 
170),
announcing
the
filing
of
a
pesticide
tolerance
petition
(
PP
2G6494)
by
Mycogen
Seeds,
c/
o
Dow
AgroSciences
LLC,
9330
Zionsville
Road,
Indianapolis,
IN
46268
 
1054.
This
notice
included
a
summary
of
the
petition
prepared
by
the
petitioner
Mycogen
Seeds,
c/
o
Dow
AgroSciences
LLC.
Comments
were
received
in
response
to
the
notice
of
filing.
These
comments
were
from
grower
groups,
state
agencies,
and
academia.
All
comments
were
in
support
of
the
registration
of
Dow
AgroSciences'
stacked
gene
plant­
incorporated
protectant.
The
petition
requested
that
40
CFR
part
180
be
amended
by
establishing
a
temporary
exemption
from
the
requirement
of
a
tolerance
for
residues
of
Bacillus
thuringiensis
Cry1F
protein
and
the
genetic
material
necessary
for
its
production
in
cotton.
New
section
408(
c)(
2)(
A)(
i)
of
the
FFDCA
allows
EPA
to
establish
an
exemption
from
the
requirement
for
a
tolerance
(
the
legal
limit
for
a
pesticide
chemical
residue
in
or
on
a
food)
only
if
EPA
determines
that
the
exemption
is
``
safe.''
Section
408(
c)(
2)(
A)(
ii)
of
the
FFDCA
defines
``
safe''
to
mean
that
``
there
is
a
reasonable
certainty
that
no
harm
will
result
from
aggregate
exposure
to
the
pesticide
chemical
residue,
including
all
anticipated
dietary
exposures
and
all
other
exposures
for
which
there
is
reliable
information.''
This
includes
exposure
through
drinking
water
and
in
residential
settings,
but
does
not
include
occupational
exposure.
Section
408(
b)(
2)(
C)
of
the
FFDCA
requires
EPA
to
give
special
consideration
to
exposure
of
infants
and
children
to
the
pesticide
chemical
residue
in
establishing
a
tolerance
and
to
``
ensure
that
there
is
a
reasonable
certainty
that
no
harm
will
result
to
infants
and
children
from
aggregate
exposure
to
the
pesticide
chemical
residue.
*
*
*''
Additionally,
section
408(
b)(
2)(
D)
of
the
FFDCA
requires
that
the
Agency
consider
``
available
information
concerning
the
cumulative
effects
of
a
particular
pesticide's
residues
and
``
other
substances
that
have
a
common
mechanism
of
toxicity.''
EPA
performs
a
number
of
analyses
to
determine
the
risks
from
aggregate
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23074
Federal
Register
/
Vol.
68,
No.
83
/
Wednesday,
April
30,
2003
/
Rules
and
Regulations
exposure
to
pesticide
residues.
First,
EPA
determines
the
toxicity
of
pesticides.
Second,
EPA
examines
exposure
to
the
pesticide
through
food,
drinking
water,
and
through
other
exposures
that
occur
as
a
result
of
pesticide
use
in
residential
settings.

III.
Toxicological
Profile
Consistent
with
section
408(
b)(
2)(
D)
of
the
FFDCA,
EPA
has
reviewed
the
available
scientific
data
and
other
relevant
information
in
support
of
this
action
and
considered
its
validity,
completeness,
and
reliability
and
the
relationship
of
this
information
to
human
risk.
EPA
has
also
considered
available
information
concerning
the
variability
of
the
sensitivities
of
major
identifiable
subgroups
of
consumers,
including
infants
and
children.
Data
were
submitted,
reviewed,
and
determined
acceptable
for
product
characterization
of
Cry1F
expressed
in
cotton
(
construct
pAGM281).
Adequate
product
characterization
data
also
were
submitted
to
demonstrate
that
the
Cry1F
protein
expressed
in
or
on
cotton
and
Cry1F
protein
expressed
in
or
on
corn
were
the
same
protein
(
Ref.
2).
The
registrant
requested
that
the
data
submitted
for
corn
(
construct
PHI
8999)
be
used
to
support
the
acute
oral
toxicity,
in
vitro
digestibility,
and
heat
stability
studies
for
Cry1F
protein
expressed
in
or
on
cotton
based
on
the
substantial
similarity
to
Cry1F
protein
expressed
in
corn
which
is
already
exempt
from
the
requirement
of
a
tolerance
(
40
CFR
180.1217).
EPA
reviewed
the
product
characterization
data
for
both
Cry1F
expressed
in
or
on
cotton
and
corn
and
determined
that
the
Cry1F
proteins
are
the
same.
Therefore,
EPA
has
concluded
that
the
data
which
supported
the
tolerance
exemption
for
Cry1F
and
its
genetic
material
necessary
for
its
production
in
corn
can
also
support
Cry1F
and
its
genetic
material
necessary
for
its
production
in
or
on
cotton.
Adequate
data
also
was
submitted
to
demonstrate
that
the
Cry1F
test
material
derived
from
microbial
cultures
was
biochemically
and,
functionally
similar
to
the
protein
produced
by
the
plantincorporated
protectant
expressed
in
cotton
(
Ref.
2).
Production
of
microbially­
produced
protein
was
chosen
in
order
to
obtain
sufficient
material
for
testing
and
because
a
diet
of
only
cotton
seed
would
not
provide
an
adequate
diet
for
test
animals.
The
FIFRA
Scientific
Advisory
Panel
has
supported
this
approach.
See
Mammalian
Toxicity
Assessment
Guidelines
for
Protein
Plant
Pesticides
(
SAP
Report
No.
2000
 
03B,
September
28,
2000)
at
http://
www.
epa.
gov/
scipoly/
sap/
2000/
June/
finbtmamtox.
pdf.
Given
that
the
Cry1F
protein
produced
in
corn
and
cotton
have
been
determined
to
be
the
same
protein,
EPA
has
determined
that
the
acute
oral
toxicity
(
MRID
numbers
446911
 
01
and
450201
 
18),
heat
stability
(
MRID
numbers
452748
 
01
and
449717
 
01),
and
in
vitro
digestibility
(
MRID
number
447149
 
03)
studies
which
support
40
CFR
180.1217
also
support
this
exemption
from
the
requirement
of
a
tolerance.
Although
Cry1F
expression
level
data
were
required
for
an
environmental
fate
and
effects
assessment,
residue
chemistry
data
were
not
required
for
a
human
health
effects
assessment
of
the
subject
plant­
incorporated
protectant
ingredients
because
of
the
lack
of
mammalian
toxicity.
Data
were
submitted
and
reviewed
which
demonstrate
the
lack
of
mammalian
toxicity
at
high
levels
of
exposure
to
the
pure
Cry1F
protein
(
Ref.
3).
These
data
adequately
demonstrate
the
safety
of
the
Cry1F
protein
at
levels
well
above
maximum
possible
exposure
levels
that
are
reasonably
anticipated
in
the
cotton
crops
(
Ref.
2).
This
is
similar
to
the
Agency
position
regarding
toxicity
and
the
requirement
of
residue
data
for
the
microbial
Bacillus
thuringiensis
products
from
which
this
plant­
incorporated
protectant
was
derived.
See
40
CFR
158.740(
b)(
2)(
i).
For
microbial
products,
further
toxicity
testing
and
residue
data
are
triggered
by
significant
acute
effects
in
studies
such
as
the
mouse
oral
toxicity
study,
to
verify
the
observed
effects
and
clarify
the
source
of
these
effects
(
Tiers
II
and
III).
Refer
to
the
Bacillus
thuringiensis
Plant­
Incorporated
Protectants
Reassessment
Biopesticide
Regulatory
Action
Document
(
BRAD)
dated
October
15,
2001
(
Ref.
3).
The
acute
oral
toxicity
data
(
MRID
numbers
446911
 
01
and
450201
 
18)
submitted
support
the
prediction
that
the
Cry1F
protein
is
non­
toxic
to
humans.
Male
and
female
mice
(
5
of
each)
were
dosed
with
15%
(
w/
v)
of
the
test
substance,
which
consisted
of
Bacillus
thuringiensis
var.
aizawai
Cry1F
protein
at
a
net
concentration
of
11.4%.
Two
doses
were
administered
approximately
an
hour
apart
to
achieve
the
dose
totaling
33.7
milliliter/
kilogram
(
mL/
kg)
body
weight.
Outward
clinical
signs
and
body
weights
were
observed
and
recorded
throughout
the
14
 
day
study.
Gross
necropsies
performed
at
the
end
of
the
study
indicated
no
findings
of
toxicity.
No
mortality
or
clinical
signs
were
noted
during
the
study.
A
lethal
dose
(
LD)
50
was
estimated
at
greater
than
5,050
mg/
kg
body
weight
of
this
microbially
produced
test
material.
The
actual
dose
administered
contained
576
mg
Cry1F
protein/
kg
body
weight.
At
this
dose,
no
LD50
was
demonstrated
as
no
toxicity
was
observed.
Cry1F
cotton
seeds
contain
0.0017
to
0.0034
mg
of
Cry1F/
gram
of
cotton
tissue
which
is
a
much
lower
level
than
the
highest
no
observable
effect
level.
When
proteins
are
toxic,
they
are
known
to
act
via
acute
mechanisms
and
at
very
low
dose
levels
(
Ref.
1).
Therefore,
since
no
effects
were
shown
to
be
caused
by
the
plant­
incorporated
protectant,
even
at
relatively
high
dose
levels,
the
Cry1F
protein
is
not
considered
toxic.
Further,
amino
acid
sequence
comparisons
showed
no
similarity
between
Cry1F
protein
to
known
toxic
proteins
available
in
public
protein
data
bases.
Since
Cry1F
is
a
protein,
allergenic
sensitivities
were
considered.
Current
scientific
knowledge
suggests
that
common
food
allergens
tend
to
be
resistant
to
degradation
by
heat,
acid,
and
proteases
may
be
glycosylated
and
present
at
high
concentrations
in
the
food
(
Ref.
3).
Data
were
submitted
and
reviewed,
and
these
data
demonstrate
that
the
Cry1F
protein
is
rapidly
degraded
by
gastric
fluid
in
vitro
and
is
non­
glycosylated.
In
a
solution
of
Cry1F:
pepsin
at
a
molar
ratio
of
1:
100,
complete
degradation
of
Cry1F
to
amino
acids
and
small
peptides
occurred
in
5
minutes.
A
heat
lability
study
demonstrated
the
loss
of
bioactivity
of
Cry1F
protein
to
neonate
tobacco
budworm
larvae
after
30
minutes
at
75
°
C.
Studies
submitted
to
EPA
using
laboratory
animals
have
not
indicated
any
potential
for
allergic
reactions
to
Bacillus
thuringiensis
or
its
components,
including
the
deltaendotoxin
of
the
crystal
protein.
Additionally,
a
comparison
of
amino
acid
sequences
of
known
allergens
uncovered
no
evidence
of
any
homology
with
Cry1F,
even
at
the
level
of
eight
contiguous
amino
acids
residues.
The
potential
for
the
Cry1F
protein
to
be
a
food
allergen
is
minimal
(
Ref.
2).
Regarding
toxicity
to
the
immune
system,
the
acute
oral
toxicity
data
submitted
support
the
prediction
that
the
Cry1F
proteins
are
non­
toxic
to
humans.
When
proteins
are
toxic,
they
are
known
to
act
via
acute
mechanisms
and
at
very
low
dose
levels
(
Ref.
1).
Therefore,
since
no
effects
were
shown
to
be
caused
by
the
plant­
incorporated
protectant,
even
at
relatively
high
dose
levels,
the
Cry1F
protein
is
not
considered
toxic.

IV.
Aggregate
Exposures
In
examining
aggregate
exposure,
section
408
of
the
FFDCA
directs
EPA
to
consider
available
information
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/
Rules
and
Regulations
concerning
exposures
from
the
pesticide
residue
in
food
and
all
other
nonoccupational
exposures,
including
drinking
water
from
ground
water
or
surface
water
and
exposure
through
pesticide
use
in
gardens,
lawns,
or
buildings
(
residential
and
other
indoor
uses).
The
Agency
has
considered
the
product
characterization
data
showing
expression
levels
of
Cry1F
protein
in
cotton
seed
exposure
levels
of
consumers
(
and
major
identifiable
subgroups
of
consumers)
to
the
pesticide
chemical
residue
and
to
other
related
substances.
These
considerations
include
dietary
exposure
under
the
tolerance
exemption
and
all
other
tolerances
or
exemptions
in
effect
for
the
plant­
incorporated
protectants'
chemical
residue,
and
exposure
from
non­
occupational
sources.
Exposure
via
the
skin
or
inhalation
is
not
likely
since
the
plant­
incorporated
protectant
is
contained
within
plant
cells,
which
essentially
eliminates
these
exposure
routes
or
reduces
these
exposure
routes
to
negligible.
Oral
exposure,
at
very
low
levels,
may
occur
from
ingestion
of
processed
cottonseed
oils
and,
potentially,
drinking
water.
However,
a
lack
of
mammalian
toxicity
and
the
digestibility
of
the
plant­
incorporated
protectants
have
been
demonstrated.
The
use
sites
for
the
Cry1F
protein
are
all
agricultural
for
control
of
insects.
Therefore,
exposure
via
residential
or
lawn
use
to
infants
and
children
is
not
expected.
Even
if
negligible
exposure
should
occur,
the
Agency
concludes
that
such
exposure
would
present
no
risk
due
to
the
lack
of
toxicity
demonstrated
for
the
Cry1F
protein.
Refer
to
the
Bacillus
thuringiensis
Reassessment
BRAD
dated
October
15,
2001.

V.
Cumulative
Effects
Pursuant
to
FFDCA
section
408(
b)(
2)(
D)(
v),
EPA
has
considered
available
information
on
the
cumulative
effects
of
such
residues
and
other
substances
that
have
a
common
mechanism
of
toxicity.
These
considerations
included
the
cumulative
effects
on
infants
and
children
of
such
residues
and
other
substances
with
a
common
mechanism
of
toxicity.
Because
there
is
no
indication
of
mammalian
toxicity
to
these
plantincorporated
protectants,
EPA
concludes
that
there
are
no
cumulative
effects
for
the
Cry1F
protein.
VI.
Determination
of
Safety
for
U.
S.
Population,
Infants
and
Children
A.
Toxicity
and
Allergenicity
Conclusions
The
product
characterization
data
are
acceptable
for
Cry1F
protein
expressed
in
cotton.
The
Agency
was
able
to
determine
that
the
Cry1F
protein
expressed
in
cotton
was
the
same
protein
as
the
Cry1F
expressed
in
corn
which
is
covered
by
an
existing
tolerance
exemption
(
40
CFR
180.1217).
Also
the
Cry1F
protein
produced
by
microbial
culture
was
biochemically
and
functionally
similar
to
the
protein
produced
by
the
plant­
incorporated
protectant
in
cotton.
Therefore,
the
Agency
was
able
to
bridge
mammalian
toxicity
data
from
a
previous
submission
for
Cry1F
protein
expressed
in
corn
to
cover
the
mammalian
toxicity
studies
required
for
Cry1F
protein
expressed
in
cotton.
These
studies
are
the
acute
oral
toxicity
(
MRID
numbers
446911
 
01
and
450201
 
18),
heat
stability,
amino
acid
homology
(
MRID
numbers
452749
 
01
and
449717
 
01)
and
in
vitro
digestibility
(
MRID
number
447149
 
03)
studies.
The
data
submitted
and
cited
regarding
potential
health
effects
for
the
Cry1F
protein
include
the
characterization
of
the
expressed
Cry1F
protein
in
corn,
as
well
as
the
acute
oral
toxicity,
heat
stability,
and
in
vitro
digestibility
of
the
proteins.
The
results
of
these
studies
were
determined
applicable
to
evaluate
human
risk
and
the
validity,
completeness,
and
reliability
of
the
available
data
from
the
studies
were
considered.
The
acute
oral
toxicity
data
submitted
supports
the
prediction
that
the
Cry1F
protein
would
be
non­
toxic
to
humans.
When
proteins
are
toxic,
they
are
known
to
act
via
acute
mechanisms
and
at
very
low
dose
levels
(
Ref.
1).
Since
no
effects
were
shown
to
be
caused
by
Cry1F
protein,
even
at
relatively
high
dose
levels
(>
5,050
mg
test
substance/
kg
body
weight;
576
mg
Cry1F/
kg
body
weight),
the
Cry1F
protein
is
not
considered
toxic.
This
is
similar
to
the
Agency
position
regarding
toxicity
and
the
requirement
of
residue
data
for
the
microbial
Bacillus
thuringiensis
products
from
which
this
plantincorporated
protectant
was
derived.
See
40
CFR
158.740(
b)(
2)(
i).
For
microbial
products,
further
toxicity
testing
and
residue
data
are
triggered
by
significant
acute
effects
in
studies
such
as
the
mouse
oral
toxicity
study
to
verify
the
observed
effects
and
clarify
the
source
of
these
effects
(
Tiers
II
and
III).
Although
Cry1F
expression
level
data
were
required
for
an
environmental
fate
and
effects
assessment,
residue
chemistry
data
were
not
required
for
a
human
health
effects
assessment
of
the
subject
plant­
incorporated
protectant
ingredients
because
of
the
lack
of
mammalian
toxicity.
Both:
available
information
concerning
the
dietary
consumption
patterns
of
consumers
(
and
major
identifiable
subgroups
of
consumers
including
infants
and
children);
and
safety
factors
which,
in
the
opinion
of
experts
qualified
by
scientific
training
and
experience
to
evaluate
the
safety
of
food
additives,
are
generally
recognized
as
appropriate
for
the
use
of
animal
experimentation
data.
The
lack
of
mammalian
toxicity
at
high
levels
of
exposure
to
the
Cry1F
protein
demonstrates
the
safety
of
the
product
at
levels
well
above
possible
maximum
exposure
levels
anticipated
in
the
crop.
Refer
to
the
Bacillus
thuringiensis
Reassessment
BRAD
dated
October
15,
2001.
Its
genetic
material
necessary
for
the
production
of
the
plant­
incorporated
protectant
active
ingredients
are
the
nucleic
acids
(
DNA,
RNA)
which
comprise
genetic
material
encoding
these
proteins
and
their
regulatory
regions.
The
genetic
material
(
DNA,
RNA)
necessary
for
the
production
of
Cry1F
protein
in
cotton
has
been
exempted
under
the
blanket
exemption
for
all
nucleic
acids
(
40
CFR
174.175).

B.
Infants
and
Children
Risk
Conclusions
FFDCA
section
408(
b)(
2)(
C)
provides
that
EPA
shall
assess
the
available
information
about
consumption
patterns
among
infants
and
children,
special
susceptibility
of
infants
and
children
to
pesticide
chemical
residues
and
the
cumulative
effects
on
infants
and
children
of
the
residues
and
other
substances
with
a
common
mechanism
of
toxicity.
In
addition,
FFDCA
section
408(
B)(
2)(
C)
also
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
margin
of
safety
will
be
safe
for
infants
and
children.
In
this
instance,
based
on
all
the
available
information,
the
Agency
concludes
that
there
is
a
finding
of
no
toxicity
for
the
Cry1F
protein
and
its
genetic
material
necessary
for
its
production
in
or
on
cotton.
Thus,
there
are
no
threshold
effects
of
concern
and,
as
a
result,
the
provision
requiring
an
additional
margin
of
safety
does
not
apply.
Further,
the
provisions
of
consumption
patterns,
special
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Rules
and
Regulations
susceptibility,
and
cumulative
effects
do
not
apply.

C.
Overall
Safety
Conclusion
There
is
a
reasonable
certainty
that
no
harm
will
result
from
aggregate
exposure
to
the
U.
S.
population,
including
infants
and
children,
to
the
Cry1F
protein
and
its
genetic
material
necessary
for
its
production
in
or
on
cotton.
This
includes
all
anticipated
dietary
exposures
and
all
other
exposures
for
which
there
is
reliable
information.
The
Agency
has
arrived
at
this
conclusion
because,
as
discussed
above,
no
toxicity
to
mammals
has
been
observed
for
the
plant­
incorporated
protectants.

VII.
Other
Considerations
A.
Endocrine
Disruptors
The
pesticidal
active
ingredients
are
proteins,
derived
from
sources
that
are
not
known
to
exert
an
influence
on
the
endocrine
system.
Therefore,
the
Agency
is
not
requiring
information
on
the
endocrine
effects
of
these
plantprotectants
at
this
time.

B.
Analytical
Method
A
method
for
extraction
and
direct
enzyme
linked
immunosorbent
assay
analysis
of
Cry1F
in
cotton
has
been
submitted
(
MRID
number
458084
 
23).
This
method
is
adequate
to
support
a
temporary
tolerance
exemption.

C.
Codex
Maximum
Residue
Level
No
Codex
maximum
residue
levels
exists
for
the
plant­
incorporated
protectants
Bacillus
thuringiensis
Cry1F
protein
and
its
genetic
material
necessary
for
its
production
in
or
on
cotton.

VIII.
Objections
and
Hearing
Requests
Under
section
408(
g)
of
the
FFDCA,
as
amended
by
the
FQPA,
any
person
may
file
an
objection
to
any
aspect
of
this
regulation
and
may
also
request
a
hearing
on
those
objections.
The
EPA
procedural
regulations
which
govern
the
submission
of
objections
and
requests
for
hearings
appear
in
40
CFR
part
178.
Although
the
procedures
in
those
regulations
require
some
modification
to
reflect
the
amendments
made
to
the
FFDCA
by
the
FQPA,
EPA
will
continue
to
use
those
procedures,
with
appropriate
adjustments,
until
the
necessary
modifications
can
be
made.
The
new
section
408(
g)
of
the
FFDCA
provides
essentially
the
same
process
for
persons
to
``
object''
to
a
regulation
for
an
exemption
from
the
requirement
of
a
tolerance
issued
by
EPA
under
new
section
408(
d),
as
was
provided
in
the
old
sections
408
and
409
of
the
FFDCA.
However,
the
period
for
filing
objections
is
now
60
days,
rather
than
30
days.

A.
What
Do
I
Need
to
Do
to
File
an
Objection
or
Request
a
Hearing?
You
must
file
your
objection
or
request
a
hearing
on
this
regulation
in
accordance
with
the
instructions
provided
in
this
unit
and
in
40
CFR
part
178.
To
ensure
proper
receipt
by
EPA,
you
must
identify
docket
ID
number
OPP
 
2003
 
0147
in
the
subject
line
on
the
first
page
of
your
submission.
All
requests
must
be
in
writing,
and
must
be
mailed
or
delivered
to
the
Hearing
Clerk
on
or
before
June
30,
2003.
1.
Filing
the
request.
Your
objection
must
specify
the
specific
provisions
in
the
regulation
that
you
object
to,
and
the
grounds
for
the
objections
(
40
CFR
178.25).
If
a
hearing
is
requested,
the
objections
must
include
a
statement
of
the
factual
issues(
s)
on
which
a
hearing
is
requested,
the
requestor's
contentions
on
such
issues,
and
a
summary
of
any
evidence
relied
upon
by
the
objector
(
40
CFR
178.27).
Information
submitted
in
connection
with
an
objection
or
hearing
request
may
be
claimed
confidential
by
marking
any
part
or
all
of
that
information
as
CBI.
Information
so
marked
will
not
be
disclosed
except
in
accordance
with
procedures
set
forth
in
40
CFR
part
2.
A
copy
of
the
information
that
does
not
contain
CBI
must
be
submitted
for
inclusion
in
the
public
record.
Information
not
marked
confidential
may
be
disclosed
publicly
by
EPA
without
prior
notice.
Mail
your
written
request
to:
Office
of
the
Hearing
Clerk
(
1900C),
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460
 
0001.
You
may
also
deliver
your
request
to
the
Office
of
the
Hearing
Clerk
in
Rm.
104,
Crystal
Mall
#
2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA.
The
Office
of
the
Hearing
Clerk
is
open
from
8
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
telephone
number
for
the
Office
of
the
Hearing
Clerk
is
(
703)
603
 
0061.
2.
Tolerance
fee
payment.
If
you
file
an
objection
or
request
a
hearing,
you
must
also
pay
the
fee
prescribed
by
40
CFR
180.33(
i)
or
request
a
waiver
of
that
fee
pursuant
to
40
CFR
180.33(
m).
You
must
mail
the
fee
to:
EPA
Headquarters
Accounting
Operations
Branch,
Office
of
Pesticide
Programs,
P.
O.
Box
360277M,
Pittsburgh,
PA
15251.
Please
identify
the
fee
submission
by
labeling
it
``
Tolerance
Petition
Fees.''
EPA
is
authorized
to
waive
any
fee
requirement
``
when
in
the
judgement
of
the
Administrator
such
a
waiver
or
refund
is
equitable
and
not
contrary
to
the
purpose
of
this
subsection.''
For
additional
information
regarding
the
waiver
of
these
fees,
you
may
contact
James
Tompkins
by
phone
at
(
703)
305
 
5697,
by
e­
mail
at
tompkins.
jim@
epa.
gov,
or
by
mailing
a
request
for
information
to
Mr.
Tompkins
at
Registration
Division
(
7505C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460
 
0001.
If
you
would
like
to
request
a
waiver
of
the
tolerance
objection
fees,
you
must
mail
your
request
for
such
a
waiver
to:
James
Hollins,
Information
Resources
and
Services
Division
(
7502C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460
 
0001.
3.
Copies
for
the
Docket.
In
addition
to
filing
an
objection
or
hearing
request
with
the
Hearing
Clerk
as
described
in
Unit
VIII.
A.,
you
should
also
send
a
copy
of
your
request
to
the
PIRIB
for
its
inclusion
in
the
official
record
that
is
described
in
Unit
I.
B.
1.
Mail
your
copies,
identified
by
docket
ID
number
OPP
 
2003
 
0147,
to:
Public
Information
and
Records
Integrity
Branch,
Information
Resources
and
Services
Division
(
7502C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460
 
0001.
In
person
or
by
courier,
bring
a
copy
to
the
location
of
the
PIRIB
described
in
Unit
I.
B.
1.
You
may
also
send
an
electronic
copy
of
your
request
via
e­
mail
to:
oppdocket
epa.
gov.
Please
use
an
ASCII
file
format
and
avoid
the
use
of
special
characters
and
any
form
of
encryption.
Copies
of
electronic
objections
and
hearing
requests
will
also
be
accepted
on
disks
in
WordPerfect
6.1/
8.0
or
ASCII
file
format.
Do
not
include
any
CBI
in
your
electronic
copy.
You
may
also
submit
an
electronic
copy
of
your
request
at
many
Federal
Depository
Libraries.

B.
When
Will
the
Agency
Grant
a
Request
for
a
Hearing?

A
request
for
a
hearing
will
be
granted
if
the
Administrator
determines
that
the
material
submitted
shows
the
following:
There
is
a
genuine
and
substantial
issue
of
fact;
there
is
a
reasonable
possibility
that
available
evidence
identified
by
the
requestor
would,
if
established
resolve
one
or
more
of
such
issues
in
favor
of
the
requestor,
taking
into
account
uncontested
claims
or
facts
to
the
contrary;
and
resolution
of
the
factual
issues(
s)
in
the
manner
sought
by
the
requestor
would
be
adequate
to
justify
the
action
requested
(
40
CFR
178.32).

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23077
Federal
Register
/
Vol.
68,
No.
83
/
Wednesday,
April
30,
2003
/
Rules
and
Regulations
IX.
References
1.
Sjoblad,
Roy
D.,
et
al.
``
Toxicological
Considerations
for
Protein
Components
of
Biological
Pesticide
Products,''
Regulatory
Toxicology
and
Pharmacology
15L,
3­
9
(
1992).
2.
U.
S.
EPA.
Memorandum,
S.
R.
Matten,
Ph.
D.
to
L.
Cole.
March
26,
2003.
3.
U.
S.
EPA.
Bacillus
thuringiensis
Plant­
Incorporated
Protectants
Reassessment
BRAD.
October
15,
2001.

X.
Statutory
and
Executive
Order
Reviews
This
final
rule
establishes
a
temporary
exemption
from
the
requirement
of
a
tolerance
under
section
408(
d)
of
the
FFDCA
in
response
to
a
petition
submitted
to
the
Agency.
The
Office
of
Management
and
Budget
(
OMB)
has
exempted
these
types
of
actions
from
review
under
Executive
Order
12866,
entitled
Regulatory
Planning
and
Review
(
58
FR
51735,
October
4,
1993).
Because
this
rule
has
been
exempted
from
review
under
Executive
Order
12866
due
to
its
lack
of
significance,
this
rule
is
not
subject
to
Executive
Order
13211,
Actions
Concerning
Regulations
That
Significantly
Affect
Energy
Supply,
Distribution,
or
Use
(
66
FR
28355,
May
22,
2001).
This
final
rule
does
not
contain
any
information
collections
subject
to
OMB
approval
under
the
Paperwork
Reduction
Act
(
PRA),
44
U.
S.
C.
3501
et
seq.,
or
impose
any
enforceable
duty
or
contain
any
unfunded
mandate
as
described
under
Title
II
of
the
Unfunded
Mandates
Reform
Act
of
1995
(
UMRA)
(
Public
Law
104
 
4).
Nor
does
it
require
any
special
considerations
under
Executive
Order
12898,
entitled
Federal
Actions
to
Address
Environmental
Justice
in
Minority
Populations
and
Low­
Income
Populations
(
59
FR
7629,
February
16,
1994);
or
OMB
review
or
any
Agency
action
under
Executive
Order
13045,
entitled
Protection
of
Children
from
Environmental
Health
Risks
and
Safety
Risks
(
62
FR
19885,
April
23,
1997).
This
action
does
not
involve
any
technical
standards
that
would
require
Agency
consideration
of
voluntary
consensus
standards
pursuant
to
section
12(
d)
of
the
National
Technology
Transfer
and
Advancement
Act
of
1995
(
NTTAA),
Public
Law
104
 
113,
section
12(
d)
(
15
U.
S.
C.
272
note).
Since
tolerances
and
exemptions
that
are
established
on
the
basis
of
a
petition
under
section
408(
d)
of
the
FFDCA,
such
as
the
temporary
exemption
in
this
final
rule,
do
not
require
the
issuance
of
a
proposed
rule,
the
requirements
of
the
Regulatory
Flexibility
Act
(
RFA)
(
5
U.
S.
C.
601
et
seq.)
do
not
apply.
In
addition,
the
Agency
has
determined
that
this
action
will
not
have
a
substantial
direct
effect
on
States,
on
the
relationship
between
the
national
government
and
the
States,
or
on
the
distribution
of
power
and
responsibilities
among
the
various
levels
of
government,
as
specified
in
Executive
Order
13132,
entitled
Federalism
(
64
FR
43255,
August
10,
1999).
Executive
Order
13132
requires
EPA
to
develop
an
accountable
process
to
ensure
``
meaningful
and
timely
input
by
State
and
local
officials
in
the
development
of
regulatory
policies
that
have
federalism
implications.''
``
Policies
that
have
federalism
implications''
is
defined
in
the
Executive
Order
to
include
regulations
that
have
``
substantial
direct
effects
on
the
States,
on
the
relationship
between
the
national
government
and
the
States,
or
on
the
distribution
of
power
and
responsibilities
among
the
various
levels
of
government.''
This
final
rule
directly
regulates
growers,
food
processors,
food
handlers
and
food
retailers,
not
States.
This
action
does
not
alter
the
relationships
or
distribution
of
power
and
responsibilities
established
by
Congress
in
the
preemption
provisions
of
section
408(
n)(
4)
of
the
FFDCA.
For
these
same
reasons,
the
Agency
has
determined
that
this
rule
does
not
have
any
``
tribal
implications''
as
described
in
Executive
Order
13175,
entitled
Consultation
and
Coordination
with
Indian
Tribal
Governments
(
65
FR
67249,
November
6,
2000).
Executive
Order
13175,
requires
EPA
to
develop
an
accountable
process
to
ensure
``
meaningful
and
timely
input
by
tribal
officials
in
the
development
of
regulatory
policies
that
have
tribal
implications.''
``
Policies
that
have
tribal
implications''
is
defined
in
the
Executive
Order
to
include
regulations
that
have
``
substantial
direct
effects
on
one
or
more
Indian
tribes,
on
the
relationship
between
the
Federal
Government
and
the
Indian
tribes,
or
on
the
distribution
of
power
and
responsibilities
between
the
Federal
Government
and
Indian
tribes.''
This
rule
will
not
have
substantial
direct
effects
on
tribal
governments,
on
the
relationship
between
the
Federal
Government
and
Indian
tribes,
or
on
the
distribution
of
power
and
responsibilities
between
the
Federal
government
and
Indian
tribes,
as
specified
in
Executive
Order
13175.
Thus,
Executive
Order
13175
does
not
apply
to
this
rule.

XI.
Congressional
Review
Act
The
Congressional
Review
Act,
5
U.
S.
C.
801
et
seq.,
as
added
by
the
Small
Business
Regulatory
Enforcement
Fairness
Act
of
1996,
generally
provides
that
before
a
rule
may
take
effect,
the
agency
promulgating
the
rule
must
submit
a
rule
report,
which
includes
a
copy
of
the
rule,
to
each
House
of
the
Congress
and
to
the
Comptroller
General
of
the
United
States.
EPA
will
submit
a
report
containing
this
rule
and
other
required
information
to
the
U.
S.
Senate,
the
U.
S.
House
of
Representatives,
and
the
Comptroller
General
of
the
United
States
prior
to
publication
of
this
final
rule
in
the
Federal
Register.
This
final
rule
is
not
a
``
major
rule
''
as
defined
by
5
U.
S.
C.
804(
2).

List
of
Subjects
in
40
CFR
Part
180
Environmental
protection,
Administrative
practice
and
procedure,
Agricultural
commodities,
Pesticides
and
pests,
Reporting
and
recordkeeping
requirements.

Dated:
April
11,
2003.
Janet
L.
Andersen,
Director,
Biopesticides
and
Pollution
Prevention
Division,
Office
of
Pesticide
Programs.


Therefore,
40
CFR
chapter
I
is
amended
as
follows:

PART
180
 
AMENDED

1.
The
authority
citation
for
part
180
continues
to
read
as
follows:

Authority:
21
U.
S.
C.
321(
q),
346(
a)
and
371.


2.
Section
180.1227
is
added
to
subpart
D
to
read
as
follows:

§
180.1227
Bacillus
thuringiensis
Cry1F
protein
and
its
genetic
material
necessary
for
its
production
in
or
on
cotton;
temporary
exemption
from
the
requirement
of
a
tolerance.

Bacillus
thuringiensis
Cry1F
protein
and
its
genetic
material
necessary
for
its
production
in
cotton
are
exempt
from
the
requirement
of
a
tolerance
when
used
as
a
plant­
incorporated
protectant
in
the
food
and
feed
commodity
of
cotton.
This
temporary
tolerance
exemption
expires
on
May
1,
2004.

[
FR
Doc.
03
 
10663
Filed
4
 
29
 
03;
8:
45
am]

BILLING
CODE
6560
 
50
 
S
ENVIRONMENTAL
PROTECTION
AGENCY
40
CFR
Part
300
[
FRL
 
7490
 
3]

National
Priorities
List
for
Uncontrolled
Hazardous
Waste
Sites
AGENCY:
Environmental
Protection
Agency.

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