May
19,
2004
FIFRA
SCIENTIFIC
ADVISORY
PANEL
(
SAP)
OPEN
MEETING
JUNE
8­
10,
2004
FIFRA
SAP
WEB
SITE
http://
www.
epa.
gov/
scipoly/
sap/
OPP
Docket
Telephone:
(
703)
305­
5805
Docket
Number:
OPP­
2004­
0146
PRODUCT
CHARACTERIZATION,
HUMAN
HEALTH
RISK,
ECOLOGICAL
RISK,
AND
INSECT
RESISTANCE
MANAGEMENT
FOR
Bacillus
thuringiensis
(
Bt)
Cotton
Products
CHARGE/
QUESTIONS
TO
THE
PANEL
WideStrike
Cotton
Questions
Product
Characterization/
Human
Health
Risk
Assessment
1.
The
Agency
examines
the
safety
of
proteins
based
on
the
source
of
the
protein,
the
protein&
rsquo;
s
pesticidal
mode
of
action,
comparisons
of
the
amino
acid
sequence
to
toxins
and
allergens
and
the
results
of
acute
oral
toxicity
testing.
The
company
provided
numerous
mammalian
oral
toxicity
studies
to
demonstrate
the
safety
of
the
introduced
Cry
1Ac
and
Cry1F
protein
insecticidal
toxins.
The
toxins
were
tested
both
separately
and
in
combination.
The
Agency
believes
tests
with
combinations
of
pure
proteins
may
address
possible
synergistic
interactions
between
introduced
proteins.
However,
the
Agency
believes
that
unless
there
is
an
indication
that
the
two
proteins
would
interact,
such
as
being
parts
of
a
binary
toxin
or
attaching
to
the
same
receptor,
there
is
little
to
justify
testing
the
two
proteins
together
when
separate
oral
toxicity
tests
indicate
a
lack
of
toxicity
for
the
individual
proteins.

Does
the
Panel
have
additional
comments
on
this
position
including
identifying
instances
where
it
would
be
justified
to
require
the
toxicity
testing
of
two
proteins
in
combination?

2.
When
traits
are
introduced
into
crop
plants
using
the
transformation
techniques
of
modern
biotechnology
or
even
traditional
breeding,
one
of
the
areas
of
concern
is
the
possibility
of
unintentional
changes.
There
is
a
general
difficulty
in
screening
for
these
unforeseen
changes
since
it
is
a
conceptual
leap
to
anticipate
the
unexpected.
However,
in
general
the
approach
has
been
to
examine
general
performance
of
the
new
cultivars
like
agronomic
performance
and
compositional
analysis
to
detect
unintentional
effects.
PIP
products
can
be
both
transformed
lines
and
the
result
of
traditional
breeding
of
two
transformed
lines
to
yield
a
new
product
with
combined
traits
like
WideStrike
cotton.
In
both
cases,
the
new
PIP
product
must
be
registered
just
as
other
new
combinations
of
pesticide
active
ingredients
must
be
registered.

For
PIP
products
resulting
from
traditionally
bred
transformed
lines,
under
what
circumstances,
if
any,
would
it
be
appropriate
to
examine
agronomic
performance
and
compositional
analysis
to
provide
a
screen
for
unintentional
changes
in
the
crop?
Please
describe
other
ways
EPA
might
consider
screening
for
potential
unintentional
changes
in
a
crop.

Ecological
Risk
Assessment
1.
WideStrike
cotton
is
a
product
expressing
pyramided
Cry1F
and
Cry1Ac
Bt
proteins.
The
submitted
non­
target
effects
studies
examined
the
effects
of
the
Cry1F
and
Cry1Ac
proteins
separately
and
in
combination
to
detect
any
synergistic
effects
on
non­
target
wildlife.
No
synergistic
effects
or
increase
in
non­
target
host
range
were
seen
as
a
result
of
combining
these
two
proteins
in
the
same
product.

The
Panel
is
requested
to
comment
on
the
need
for
non­
target
hazard
data
development
on
the
combinations
of
Cry
proteins
being
considered
for
registration
when
data
on
the
effects
of
the
individual
Cry
proteins
are
readily
available
and
show
no
adverse
effects.

2.
The
weight
of
evidence
from
the
reviewed
data
indicates
that
there
will
not
be
a
hazard
to
wildlife
from
the
commercialization
of
WideStrike
cotton.
Although
the
Bt
proteins
expressed
by
WideStrike
are
known
to
affect
only
lepidopteran
insect
species,
the
Agency
evaluated
studies
of
potential
effects
on
a
wide
variety
of
non­
target
organisms
that
might
be
exposed
to
the
Cry1F
and
Cry1Ac
protein,
i.
e.,
wild
mammals,
birds,
invertebrates,
and
aquatic
species.
EPA
concluded
that
aquatic
and
terrestrial
wildlife
was
not
likely
to
be
harmed
and
that
WideStrike
cotton
was
not
likely
to
threaten
the
long­
term
survival
of
any
non­
target
wildlife
populations.

The
Panel
is
requested
to
comment
on
the
Agency's
analysis
of
the
currently
available
data
on
the
potential
impacts
of
WideStrike
cotton
on
non­
target
species.

3.
The
Agency
has
sufficient
information
to
conclude
that
there
is
no
hazard
from
the
proposed
uses
of
WideStrike&
trade;
cotton
to
non­
target
wildlife,
aquatic
and
soil
organisms.
However,
the
Agency
is
requesting
additional,
primarily
long
term
effects
data
that
were
recommended
by
previous
Panels
for
PIP
corn.
The
supplementary
studies
would
provide
additional
weight
to
support
the
Agency's
conclusions.

The
Panel
is
asked
to
comment
on
(
a)
the
scientific
value
of
the
proposed
additional
studies
that
are
identified
at
the
end
of
the
Environmental
Assessment
section,
including
avian
chronic
exposure
testing
and
multi­
year
field
and
soil
persistence/
terrestrial
expression
studies,
and
(
b)
the
applicability
of
these
data
to
PIP
cotton.
Insect
Resistance
Management
1.
Dose.
Three
methods
(
two
laboratory
and
one
field)
outlined
by
USEPA&
rsquo;
s
Scientific
Advisory
Panel
(
1998)
were
used
to
demonstrate
that
WideStrike
cotton
expresses
a
high
dose
of
Cry1Ac
and
Cry1F
against
tobacco
budworm
(
Heliothis
virescens,
TBW).
Dow
AgroSciences
(
Dow)
employed
one
laboratory­
based
and
one
field­
based
method
to
demonstrate
that
WideStrike
cotton
has
a
high
dose
(
Cry1Ac
only,
Cry1F
is
non­
toxic)
against
pink
bollworm
(
Pectinophora
gossypiella,
PBW)
Results
of
two
field
studies
indicate
that
WideStrike
cotton
produces
a
moderate
dose
against
cotton
bollworm
(
Helicoverpa
zea,
CBW),
but
a
very
high
level
of
control
(
94%).
The
Agency
concluded
that
WideStrike
cotton
expresses
a
high
dose
of
Cry1F
and
Cry1Ac
against
TBW
(
Cry1Ac
alone
expresses
a
high
dose
and
Cry1F
a
nearly
high
dose);
a
moderate
dose
of
Cry1F
and
Cry1Ac
against
CBW,
and
a
high
dose
of
Cry1Ac
against
pink
bollworm.

The
Agency
asks
the
SAP
to
comment
on
the
Agency&
rsquo;
s
analysis
of
dose
for
TBW,
CBW,
and
PBW,
the
likelihood
that
resistance
will
be
inherited
as
a
recessive
trait,
and
its
impact
on
insect
resistance
management
for
WideStrike
cotton.

2.
Cross­
resistance.
Resistance
to
Bt
proteins
can
occur
through
several
different
mechanisms.
Alteration
of
binding
receptors
has
been
the
most
common
mechanism
observed.
The
binding
patterns
of
the
Cry1F
and
Cry1Ac
proteins
in
CBW
and
TBW
indicate
there
are
shared
and
unique
binding
sites.
In
TBW,
Cry1Ac
binds
to
at
least
three
receptors,
while
Cry1F
binds
to
at
least
two,
only
one
of
which
binds
Cry1Ac.
In
CBW,
Cry1Ac
and
Cry1F
each
bind
to
at
least
four
receptors,
of
which
two
are
shared.
For
CBW,
approximately
60%
of
Cry1Ac
binding
is
to
receptors
that
also
bind
Cry1F,
and
the
remaining
40%
of
Cry1Ac
binding
is
to
receptors
that
do
not
bind
Cry1F.
Incomplete
shared
binding
is
expected
to
lead
to
incomplete
cross­
resistance
when
resistance
is
mediated
by
receptor
changes.
Thus,
a
mutation
in
a
gene
that
codes
for
a
receptor
that
binds
both
insecticidal
control
proteins
(
ICPs)
will
not
prevent
all
binding
of
either
ICP
and
thus
alone
will
not
allow
high
survival
of
the
insect
bearing
even
two
copies
of
it,
on
WideStrike
(
Cry1F/
Cry1Ac)
cotton
plants.

The
Agency
asks
the
SAP
to
comment
on
EPA&
rsquo;
s
conclusion
that
incomplete
shared
binding
of
Cry1Ac
and
Cry1F
receptors,
in
TBW
and
CBW,
is
expected
to
lead
to
incomplete
cross­
resistance
and
thus
the
likelihood
of
enhanced
survival
on
WideStrike
cotton
is
expected
to
be
small.
Please
comment
on
EPA&
rsquo;
s
conclusion
that
resistance
is
more
likely
to
be
associated
with
receptor
binding
modifications
rather
than
other
mechanisms
of
resistance
such
as
detoxification
in
the
midgut
lumen
by
proteases
that
cleave
the
insecticidal
control
protein(
s),
metabolic
adaptations,
protease
inhibition,
gut
recovery,
and
behavioral
adaptations.

3.
CBW
modeling.
Dow&
rsquo;
s
CBW
modeling
efforts
show
that
EPA
can
have
high
confidence
that
there
will
not
be
a
significant
change
in
population
fitness
of
CBW
on
WideStrike
cotton
in
a
15­
year
time
horizon
even
without
a
high
dose
for
either
Cry1Ac
or
Cry1F
and
incomplete
cross­
resistance
(
20
to
60%
maximum
shared
binding).
Market
share
analysis
of
WideStrike
cotton
versus
other
Bt
cotton
products
had
little
effect
on
the
rate
at
which
CBW
may
adapt
in
either
the
North
Carolina
or
Mississippi
Delta
agroecosystem.
Refuge
size,
whether
sprayed
or
unsprayed,
had
no
significant
impact
on
CBW
population
fitness
on
WideStrike
cotton
after
15
years.
In
the
Delta,
the
immigrating
non­
selected
population
from
alternate
hosts
further
reduces
the
local
rate
of
adaptation.
The
local
structured
refuge
only
supplies
a
small
proportion
of
the
non­
selected
insects
in
the
Delta.
The
availability
of
CBW
alternate
hosts,
coupled
with
a
non­
Bt
cotton
refuge
are
additional
levels
of
assurance
for
WideStrike
cotton
product
durability.
Additional
empirical
information
is
needed
on
the
function
and
effectiveness
of
alternate
hosts
on
the
rate
of
CBW
adaption.

The
Agency
asks
the
SAP
to
comment
on
the
predictions
made
by
the
DAS
CBW
model,
i.
e.,
the
likelihood
that
the
population
fitness
of
CBW
on
WideStrike
cotton
in
a
15­
year
time
horizon
will
remain
unchanged,
even
without
a
high
dose
for
either
Cry1Ac
or
Cry1F
and
incomplete
cross­
resistance
(
60%
of
Cry1Ac
binds
to
the
Cry1F
receptor).

4.
TBW
modeling.
For
TBW,
durability
is
expected
to
be
greater
than
that
predicted
using
the
TBW
model
by
Peck
et
al.
(
1999)
where
the
worst
case
(
structured
refuge
is
moved
each
year)
is
17
years.
TBW
exhibits
similar
patterns
in
binding
studies
as
does
CBW
and
WideStrike
cotton
expresses
a
high
dose
against
TBW.
The
Cry1Ac
component
alone
is
a
high
dose
and
the
Cry1F
component
alone
is
not
quite
a
high
dose.

The
Agency
asks
the
SAP
to
comment
on
the
relative
WideStrike
cotton
durability
against
TBW
using
the
Peck
et
al.
(
1999)
model.

5.
Alternate
hosts.
Dow
utilizes
its
CBW
model
that
simulates
two
agroecosystems
that
consist
of
CBW
crops
hosts
soybean,
maize,
and
cotton
in
varying
amounts,
three
insecticidal
control
proteins
(
Cry1Ac,
Cry1F,
and
Cry2Ab),
and
three
protein
receptors.
Dow
also
uses
the
HOSTS
data
base,
and
carbon
isotope
work
by
Gould
et
al.
(
2002)
to
support
the
use
of
CBW
alternate
hosts
as
an
effective
means
of
reducing
the
population­
wide
selection
pressure
to
the
two
ICPs
expressed
in
WideStrike
cotton
(
metapopulation
dynamics
effects).
To
support
the
effectiveness
of
alternate
hosts
as
natural
refugia,
data
are
needed
on
the
larval
and
adult
production
of
CBW
on
each
alternate
host
for
each
generation
relative
to
cotton
and
WideStrike
cotton
and
the
spatial
scale
and
source
of
moth
production.

The
Agency
asks
the
SAP
to
comment
on:
a)
the
sufficiency
of
the
WideStrike
cotton
database
to
address
the
issue
of
CBW
alternate
hosts
as
natural
refugia,
and,

b)
whether
additional
data
are
needed
on
the
larval
and
adult
production
of
CBW
on
each
alternate
host
for
each
generation
relative
to
cotton
and
WideStrike
cotton
and
the
spatial
scale
and
source
of
moth
production
to
confirm
the
effectiveness
of
CBW
alternate
hosts
as
natural
refugia.

6.
IRM
Plan.
The
WideStrike
cotton
IRM
plan
has
the
following
proposed
refuge
requirements:

a.
5%
external
unsprayed
refuge
option.
Five
percent
of
the
cotton
fields
must
be
planted
to
non­
Bt
cotton
and
not
be
treated
with
any
lepidopteran­
control
technology.
The
refuge
must
be
at
least
150
ft.
wide
(
preferably
300
ft.)
and
within
½
mile
(
preferably
adjacent
or
within
1/
4
mile
or
closer)
of
the
Bt
cotton.

b.
20%
external
sprayable
refuge
option.
Twenty
percent
of
the
cotton
fields
must
be
planted
to
non­
Bt
cotton
and
may
be
treated
with
lepidopteran­
active
insecticides
(
or
other
control
technology)
except
for
microbial
Bt
formulations.
The
refuge
must
be
within
1
mile
(
preferably
within
½
mile
or
closer)
of
the
Bt
cotton
fields.

c.
5%
embedded
refuge
option
for
TBW
and
CBW.
Five
percent
of
a
cotton
field
(
or
fields)
must
be
planted
with
non­
Bt
cotton
as
a
block
within
a
single
field,
at
least
150
ft.
wide
(
preferably
300
ft.
wide)
or
single­
field
blocks
within
a
one
mile
squared
field
unit.
The
refuge
may
be
treated
with
lepidopteran­
active
insecticides
(
or
other
control
technology)
only
if
the
entire
field
or
field
unit
is
treated
at
the
same
time.

d.
Embedded
(
in­
field
strip)
refuge
option
for
PBW.
One
single
row
of
a
non­
Bt
cotton
variety
must
be
planted
for
every
6
to
10
rows
of
Bt
cotton.
This
can
be
treated
with
lepidopteran­
active
insecticides
(
or
other
control
technology)
only
if
the
entire
field
is
treated
at
the
same
time.

e.
Community
refuge
option.
Farmers
can
combine
neighboring
fields
within
a
one­
mile
squared
field
unit
that
act
as
a
20%
sprayable
refuge
or
the
5%
unsprayed
refuge.
Participants
in
the
community
refuge
option
must
have
a
community
refuge
coordinator,
and
appropriate
documentation
is
required.
It
also
includes
the
requirements
for
annual
resistance
monitoring,
annual
compliance
assurance
program,
grower
education,
remedial
action
plans,
and
annual
reporting.
Any
plan
that
focuses
on
TBW,
CBW,
and
PBW
should
be
adequate
to
maintain
susceptibility
in
secondary
pests,
such
as
fall
armyworm,
beet
armyworm,
southern
armyworm,
cabbage
looper,
and
soybean
looper.
A
market
mix
of
different
Bt
cottons
and
other
control
technologies
further
reduces
the
expected
selection
pressure
for
resistance
from
the
Cry1F
and
Cry1Ac
proteins
expressed
in
WideStrike
cotton.

The
Agency
asks
the
SAP
to
comment
on
the
scientific
data
available
to
support
the
proposed
IRM
plan
and
whether
that
data
support
a
delay
in
resistance
of
TBW,
CBW,
and
PBW
resistance
to
the
Cry1F
and
Cry1Ac
proteins
expressed
in
WideStrike
cotton
for
at
least
15
years.

Bollgard
and
Bollgard
II
cotton
IRM:
Cotton
Bollworm
IRM
Questions
As
a
condition
of
the
Bollgard
and
Bollgard
II
registrations,
EPA
required
that
the
Monsanto
Company
conduct
CBW
alternate
host
research
studies
and
pyrethroid
overspray
studies
to
support
the
adequacy
of
the
5%
external,
unsprayed,
structured
refuge.
In
addition,
EPA
required
that
the
Monsanto
Company
conduct
research
on
the
north­
south
movement,
i.
e.,
reverse
migration,
of
CBW
and
its
impact
on
Bt
corn
and
cotton
insect
resistance
management.

1.
North­
south
movement.
Based
on
the
modeling
studies
submitted
using
the
data
in
Gould
et
al.
(
2002),
CBW
(
also
called
corn
earworm
in
corn)
reverse
migration
has
no
significant
impact
(
0.05<
P)
on
CBW
adaptation
to
Bt
corn
and
cotton.

The
Agency
requests
that
the
SAP
comment
on
whether
CBW
reverse
migration
is
expected
to
have
any
significant
impact
on
CBW
adaptation
to
Bt
crops.

2.
Pyrethroid
oversprays.
Pyrethroid
oversprays
in
Bollgard
cotton
fields
will
increase
the
level
of
control
of
CBW,
delay
the
evolution
of
resistance,
and
increase
the
relative
effectiveness
of
the
5%
external,
unsprayed,
structured
refuge.
These
findings
support
the
general
predictions
of
the
Gustafson
et
al.
(
2001/
2004)
model.
Pyrethroid
sprays
on
Bollgard
II
plots
do
not
provide
a
statistically
significant
difference
in
reduction
of
CBW
infestation
or
damage
from
untreated
Bollgard
II
cotton
fields
or
from
treated
Bollgard
cotton
fields,
and
should
not
be
included
as
a
parameter
in
the
Gustafson
et
al.
(
2004)
model.

a.
The
Agency
requests
that
the
SAP
comment
on
whether
pyrethroid
oversprays
in
Bollgard
cotton
fields
are
likely
to
increase
the
level
of
control
of
CBW,
delay
the
evolution
of
resistance,
and
increase
the
relative
effectiveness
of
the
5%
external,
unsprayed,
structured
refuge.

b.
The
Agency
also
requests
that
the
SAP
comment
on
EPA&
rsquo;
s
recommendation
that
pyrethroid
oversprays
not
be
included
as
a
parameter
in
the
Gustafson
et
al.
(
2004)
model
for
Bollgard
II.

c.
Marcus
et
al.
(
2004)
found
that
CBW
larvae
(
late
instars)
in
North
Carolina
Bollgard
plots
were
half
as
susceptible
to
Cry1Ac
(
i.
e.,
more
tolerant)
as
were
populations
from
non­
Bollgard
cotton
survivors
in
the
F1
generation.

The
Agency
requests
the
SAP
comment
on
whether
the
cotton
bollworm
larvae
coming
from
Bollgard
fields
are
more
tolerant
to
the
Cry1Ac
protein
than
those
larvae
coming
from
the
non­
Bollgard
fields.
What,
if
any,
additional
genetic
work
should
be
conducted
to
better
understand
the
nature
of
this
Cry1Ac
tolerance.

d.
The
Agency
requests
the
SAP
to
comment
on
the
value
of
using
a
Cry1Ac­
resistant
CBW
colony
to
investigate
the
genetic
basis
for
CBW
survival
on
Bollgard
cotton.

3.
Alternate
hosts.
Based
on
the
two­
year,
studies
in
five
states,
both
C3
and
C4
alternate
hosts
serve
as
unstructured
refugia.
Data
show
that
CBW
moths
are
produced
on
alternate
hosts
throughout
the
landscape
(
spatial
scale
is
greater
than
10
miles)
in
sufficient
numbers
throughout
the
cotton
growing
season
to
mate
with
any
putative
resistant
CBW
moths
emerging
in
Bollgard
or
Bollgard
II
cotton
fields
and
dilute
resistance.
That
is,
the
susceptible
CBW
moths
coming
from
alternate
hosts
will
reduce
the
intensity
of
Cry1Ac
and
Cry2Ab2
resistance
selection
in
CBW
and
lower
the
likelihood
of
resistance
evolution.
The
contribution
of
susceptible
CBW
adults
from
alternate
hosts
is
greater
than
that
from
the
5%
external,
unsprayed,
structured
non­
Bt
cotton
refuge.
Despite
the
limitations
EPA
has
identified
associated
with
the
Gustafson
et
al.
(
2001/
2004)
model,
the
CBW
alternate
host
data
support
the
model&
rsquo;
s
predictions
that
alternate
hosts
will
substantially
delay
resistance.

a.
Based
on
the
larval
productivity
analyses,
adult
productivity
analyses,
and
satellite
imaging
analysis,
the
Agency
asks
the
SAP
to
comment
on
the
relative
contribution
of
the
C3
and
C4
alternate
hosts
as
unstructured
refugia
to
dilute
CBW
resistance.

b.
Based
on
the
data,
the
Agency
also
asks
the
SAP
to
comment
on
the
spatial
and
temporal
scale
across
the
landscape,
e.
g.,
1
mile,
10
mile
etc.,
in
which
CBW
adult
production
should
be
evaluated.

c.
EPA
concludes
that
&
ldquo;
effective
refuge
size&
rdquo;
should
be
a
weighted
average
of
the
proportion
of
moths
coming
from
each
alternate
host
for
each
CBW
generation
(
5
to
6
generations)
in
each
cotton
production
system
(
geography).

The
Agency
asks
the
SAP
to
comment
on
how
to
quantitatively
or
semi­
quantitatively
calculate
&
ldquo;
effective
refuge
size&
rdquo;
locally
and
regionally
using
available
data
(
see
above).

4.
Gustafson
et
al.
CBW
model.
Monsanto
modified
Caprio&
rsquo;
s
(
1998a)
two­
patch,
deterministic,
non­
random,
population
genetics
model
(
publically
available)
to
create
a
new
CBW
model,
Gustafson
et
al.
(
2004,
originally
submitted
to
the
Agency
in
September
2001
as
part
of
the
Bt
Crops
Reassessment)
that
included
alternate
hosts
and
synthetic
pyrethroid
oversprays
as
parameters.
Sensitivity
analyses
showed
that
the
model
output
(
years
to
resistance)
was
sensitive
to
both
of
these
parameters.
Gustafson
et
al.
(
2004)
have
calculated
&
ldquo;
effective
refuge
size&
rdquo;
as
the
sum
of
the
total
acres
by
county
represented
by
the
four
alternate
crop
hosts
&
ndash;
corn,
sorghum,
peanuts,
and
soybeans,
and
wild
hosts
(
defaulted
as
10%
of
the
cotton
acreage)
as
a
percent
of
cotton
acres.
This
model
predicts
that
the
5%
external,
unsprayed,
structured
refuge
option
is
adequately
protective
to
delay
CBW
resistance
if
effective
refuge
size
(
alternate
hosts)
and
typical
use
practices
for
Bollgard
cotton,
i.
e.,
synthetic
pyrethroid
oversprays,
are
included.
When
this
model
was
submitted
to
the
Agency
in
2001,
empirical
data
to
support
the
use
of
alternate
hosts
and
synthetic
pyrethroid
were
lacking.

a.
The
Agency
asks
the
SAP
to
comment
on
the
&
ldquo;
effective
refuge
size&
rdquo;
calculation.
Does
the
SAP
agree
with
the
Agency&
rsquo;
s
conclusion
that
&
ldquo;
effective
refuge
size&
rdquo;
is
a
weighted
average
of
the
proportion
of
moths
coming
from
each
alternate
host
for
each
CBW
generation
(
5
to
6
generations)
in
each
cotton
production
system
(
geography)?

b.
The
Agency
requests
the
SAP
to
comment
on
the
strengths
and
weaknesses
of
the
Gustafson
et
al.
(
2004)
model
and
its
utility
with
regard
to
the
effective
contribution
of
alternate
hosts
as
natural
refuge
per
generation.
How
would
the
model
output
be
altered
if
the
calculation
of
&
ldquo;
effective
refuge
size&
rdquo;
is
changed
(
see
a.
above).
What
are
the
SAP&
rsquo;
s
recommendations
for
refining
the
Gustafson
et
al.
(
2004)
CBW
resistance
management
model
or
using
a
different
CBW
resistance
management
model
to
more
appropriately
consider
the
spatial
and
temporal
dynamics
of
CBW
utilization
of
alternative
hosts
by
generation
based
on
the
data
in
Head
and
Voth
(
2004)?

c.
The
Agency
requests
the
SAP
to
comment
on
validity
of
using
the
average
pyrethroid
efficacy
value
against
CBW
based
on
all
the
field
studies
conducted
in
all
four
states
(
North
Carolina,
Louisiana,
Mississippi,
and
South
Carolina)
as
the
parameter
value
in
the
Gustafson
et
al.
(
2004)
model
rather
than
just
the
Brickle
et
al.
(
2001)
data
from
South
Carolina.
