1
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
OCT
24
2003
NOTE
TO
FILE
SUBJECT:
Requirement
for
Acute
Oral
Toxicity
Testing
of
Combination
of
Cry1Ab
and
Cry
3Bb1
Proteins
for
Yield
gard
Plus
Corn
TO:
Mike
Mendelsohn
Regulatory
Action
Leader
Microbial
Pesticides
Branch,
Biopesticides
and
Pollution
Prevention
Division
(
7511C)

FROM:
John
L.
Kough,
Ph.
D.,
Biologist
Chris
A.
Wozniak,
Ph.
D.,
Plant
Patholgoist
Microbial
Pesticides
Branch,
Biopesticides
and
Pollution
Prevention
Division
(
7511C)

DATA
REVIEW
RECORD
Active
Ingredient:
Cry1Ab/
Cry3Bb1
proteins
as
expressed
in
maize
Product
Name:
Event
MON
810
x
MON
863
traditional
cross
hybrid,
Yieldgard
Plus
corn
Company
Name:
Monsanto
Corporation,
700
Chesterfield
Pkwy,
St.
Louis,
MO
ID
No:
000524­
LUL
Chemical
Number:
006484
Submission
Number:
S627345
DP
Barcode:
D287601
BACKGROUND:
Monsanto
Corporation
is
seeking
a
registration
to
sell
a
corn
product
expressing
two
insecticidal
proteins
based
on
 ­
endotoxins
found
in
Bacillus
thuringiensis
species.
Unlike
some
other
products
under
consideration,
the
Monsanto
Yieldgard
Plus
corn
expresses
 ­
endotoxins
aimed
at
controlling
insect
pests
from
two
different
orders,
is
supported
by
toxicity
data
for
each
protein
generated
by
the
company
itself,
has
existing
food
tolerance
exemptions
in
place
and
was
developed
through
traditional
hybrid
cross
plant
breeding.
2
DISCUSSION:
The
presence
of
two
or
more
newly
expressed
proteins
in
a
genetically
engineered
plant
is
not
expected
to
routinely
require
additional
toxicity
testing
if
there
are
existing
data
to
demonstrate
the
safety
of
the
individual
proteins
and
a
food
tolerance
determination
has
been
made.
This
rationale
is
similar
to
that
employed
for
the
current
products
which
often
consist
of
both
an
expressed
pesticidal
protein
and
a
marker
gene
protein
expressed
in
a
single
plant.
There
may
be
instances
where
information
available
on
the
mode
of
action
of
the
proteins
would
indicate
the
likelihood
that
the
combination
of
proteins
should
be
evaluated
and
the
Agency
reserves
the
right
to
test
combinations
in
those
instances.

RECOMMENDATION:
The
data
generated
for
the
Cry1Ab
and
Cry3Bb1
proteins
individually
can
support
a
food
tolerance
determination
for
the
combination
since
the
mode
of
action
for
these
proteins
does
not
suggest
an
enhanced
activity
in
combination
for
mammalian
species.
This
lack
of
synergism
is
also
suggested
by
the
absence
of
enhanced
responses
in
sensitive
target
species
tested
with
the
combination
of
Cry1Ab
and
Cry3Bb1proteins.
