Document ID: EPA-HQ-OPP-2007-0574-0004
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-12-05T05:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY   

           WASHINGTON, D.C. 20460

	

				NOV 13 2007		

OFFICE OF PREVENTION,                                              
PESTICIDES AND TOXIC                                                    
                   SUBSTANCES 

      

MEMORANDUM

SUBJECT:	Review of Application to extend the existing temporary
exemption from the requirement of tolerance for Vip3Aa20 Bacillus
thuringiensis (Bt) insect control protein [40 CFR Part 174.528] and to
amend the Experimental Use Permit [EPA Reg. No. 67979-EUP-6] for
plant-incorporated protectants in corn events  MIR162, Bt11, MIR604, and
combined insecticidal trait corn hybrids Bt11 x MIR162, MIR162 x MIR604,
and Bt11 x MIR162 x MIR604, produced by conventional breeding; submitted
by Syngenta Seeds, Inc. – Field Crops- NAFTA.

TO:		Mike Mendelsohn, Regulatory Action Leader

		Microbial Pesticides Branch, Biopesticides and

		Pollution Prevention Division (7511P)

FROM:	Annabel Waggoner, Environmental Protection Specialist	[signed]

		Microbial Pesticides Branch, Biopesticides and		

		Pollution Prevention Division (7511P)

PEER		John L. Kough, Ph.D., Senior Scientist				[signed]

REVIEW:	Microbial Pesticides Branch, Biopesticides and			

		Pollution Prevention Division (7511P); and

		Zigfridas Vaituzis, Ph.D., Senior Scientist			[signed]

		Microbial Pesticides Branch, Biopesticides and			

		Pollution Prevention Division (7511P)

ACTION REQUESTED: To review Syngenta Seeds, Inc.’s application to
amend the Experimental Use Permit [EPA Reg. No. 67979-EUP-6] and extend
the existing temporary exemption from the requirement of tolerance [40
CFR Part 174.528] for Vip3Aa20 Bt insect control protein as expressed in
Event MIR162 corn and all corresponding events used in field testing in
conjunction with the EUP.

CONCLUSION:    The Agency previously concluded there is a reasonable
certainty of no harm to humans from the aggregate exposure to the
residues of theVip3Aa20, including all anticipated dietary exposures and
all other exposures for which there is reliable information.  It was
also concluded that it is unlikely that direct or indirect harmful
effects to non-target organisms (NTOs), including Federally listed
endangered species, would result from exposure to the insecticidal
protein Vip3Aa20 during the proposed field trials as outlined in the EUP
for MIR162 corn.  For the purposes of the EUP, the Agency continues to
support its original conclusions.  Since there are no new data concerns
of Vip3Aa20 since the granting of the EUP, these data can support the
extension of the EUP [EPA Reg. No. 67979-EUP-6] and the temporary
tolerance exemption [40 CFR 174.528] for the period of March 2008
through October 31, 2009.

DATA REVIEW RECORD:

Active Ingredient:		Vip3Aa20 Bacillus thuringiensis insecticidal protein
and the genetic material necessary for its production (via pNOV1300) in
transgenic corn plants derived from transformation Event MIR162 

Product Name(s):		Event MIR162 corn and combined insecticidal trait corn
hybrids: Bt11 x MIR162, MIR162 x MIR604, and Bt11 x MIR162 x MIR604 

Company Name:			Syngenta Seeds, Inc. – Field Corps- NAFTA

ID No:				67979

Chemical Number:	 	006599

Decision Number:		379040

DP Barcode:			340414						

MRID No:			Not-Assigned- Administrative Materials:  Application to amend
Experimental Use Permit [EPA Reg. No. 67979-EUP-6] and Petition to
extend the temporary tolerance exemption from the requirement of
tolerance (40 CFR 174.528, Petition No. 7F212).

BACKGROUND:

Vip3A is a vegetative insecticidal protein (Vip) from Bacillus
thuringiensis (Bt), a gram positive bacterium commonly found in soil. 
Vip proteins are produced during the vegetative stage of bacterial
growth and are active against the following lepidopteran pests of corn: 
Spodoptera frugiperda (fall armyworm), Pseudaletia unipunctata
(armyworm), Spodoptera exigua (beet armyworm), Helicoverpa zea (corn
earworm / cotton bollworm), Agrotis ipsilon (black cutworm), and
Striacosta albicosta (western bean cutworm).   

The native Vip protein, Vip3Aa1, was isolated from Bt strain AB88 and
characterized by Estruch et al. in 1996.  Syngenta engineered a variant
of the native gene for incorporation into corn.  This engineered gene
has been designated, vip3Aa20, and it was stably incorporated (via
pNOV1300 vector) into the genome of Event MIR162 corn by
Agrobacterium-mediated transformation.  Event MIR162 corn also contains
the pmi gene, which was introduced along with the Vip3Aa20 protein via
the same pNOV1300 transformation vector.  The gene represents the manA
gene from Escherichia coli and encodes the enzyme phosphomannose
isomerase (PMI), which was employed as a selectable marker during the
process of regenerating plant material following transformation
(Negrotto, et al., 2000).  

On March 27, 2007, EPA issued an experimental permit for the use Bt
Vip3Aa20 protein in Event MIR162 corn and associated activities (such as
breeding and observation, insect efficacy evaluation, agronomic
observation, inbred and hybrid seed production, and regulatory studies)
through March 18, 2008.  Planting proposed under the EUP took place in
22 states and Puerto Rico for a total of 3,099 acres of field corn.     
 

In conjunction with the EUP, the Agency also established a temporary
exemption from the requirement of a tolerance for Vip3Aa20 and the
genetic material necessary for their production in corn which will
expire March 31, 2008 [see 40 CFR 174.528 (72 FR 20435, dated Apr. 25,
2007)]. To support their requests for EUP and a temporary tolerance
exemption, Syngenta Seeds, Inc. submitted product characterization,
human health and environmental fate and effects data.  These data were
reviewed and found acceptable by the Agency (EPA, 2007a and 2007b).  

In this report, Syngenta Seeds, Inc. is seeking an extension and
amendment of its current  EUP [EPA Reg. No. 67979-EUP-6] to allow:  1)
continued field planting of the Vip3Aa20 Bt insect control protein in
Event MIR162-derived field corn plants, and 2) the further large-scale
field testing of conventional breeding ‘stacks’ of Event MIR162 corn
with Event Bt11 corn expressing a Cry1Ab Bt insect control protein
(MIR162 x Bt11 corn), Event MIR162 with Event MIR604 corn expressing
mCry3A Bt insect control protein (MIR162 x MIR604), as well as the
combined insecticidal trait corn hybrids (MIR162 x Bt11 x MIR604).  By
combining the MIR162, Bt11, and MIR604 via conventional breeding, corn
hybrids produce Vip3Aa20 and Cry1Ab proteins for control of key
lepidopteran pests and mCry3A protein for control of key coleopteran
pests.  Syngenta is requesting authorization to amend the EUP for
continued plantings and associated field activities for 31 states and
Puerto Rico for a total of 4,844 acres of field corn in 2008 and 4,856
acres in 2009 and extend the temporary tolerance exemption through
October 31, 2009.  

The purpose of this report is to confirm that the previously submitted
product characterization, human health, and environmental fate and
effects data can support the extension and amendment to the EUP and
temporary tolerance exemption and that there are no new data concerns
for the purposed of the EUP.  For Sec. 3 registration and full
commercial cultivation of MIR162 corn and its associated breeding
stacks, Syngenta Seeds, Inc. submitted additional data and these data
are currently under Agency review.

SUMMARY OF DATA:

The Agency previously concluded that, “there is a reasonable certainty
that no harm will result from aggregate exposure to the U.S. population
to Vip3Aa20 protein and the genetic material necessary for its
production” (EPA, 2007a) for the EUP of MIR162 corn.  Since the
granting of the EUP, there have been no new data that indicates a
potential for adverse effects on humans,  therefore, the Agency supports
its original conclusions for the purposes of this EUP.

It was also previously concluded that, “it is unlikely that direct or
indirect harmful effects to non-target organisms (NTOs), including
Federally listed endangered species, would result from exposure to the
insecticidal protein Vip3Aa20, which is expressed in MIR162 corn,” nor
its associated breeding stacks, as a result of the proposed field trials
outlined in the EUP for MIR162 corn (EPA, 2007b).  Although Syngenta
Seeds, Inc. is requesting an increase of acreage and additional states
for further field testing sites, the limited exposure of these plants
would result in minimal risk to the overall populations of the NTOs due
to the small acreage of the trials in the amended EUP, the continued
containment procedures, and disposition of plant materials. 
Furthermore, there are no new data that indicates a potential of adverse
effects on non-target organisms since the granting of the EUP,
therefore, the Agency supports its original conclusions for the purposes
of the amended EUP.  

CONCLUSION:

The previously reviewed data submitted for the original EUP for MIR162
corn and its breeding stacks are sufficient to support the amendment and
extension of the EUP [EPA Reg. No. 67979-EUP-6] and the temporary
exemption from the requirement of tolerance for Vip3Aa20 [40 CFR
174.528] for the period of March 2008 through October 31, 2009. 

REFERENCES:

EPA, 2007a.  “Review of Product Characterization and Human Health Data
for Plant- Incorporated 

Protectant Bacillus thuringiensis (Bt) Vip3Aa20 insect control protein
(EPA Reg. No. 67979-EUP-A) and the genetic material necessary for its
production in Event MIR162 corn in support for a temporary exemption
from tolerances and Experimental Use Permit (EUP).” Memorandum- from A
Waggoner, through J. Kough, Ph.D., to M. Mendelsohn, dated Feb. 8, 2007.

EPA, 2007b.  “Environmental effects risk assessment for Syngenta’s
MIR162 Bt corn EUP.” 

	Memorandum- from T. Milofsky, through Z. Vaituzis, to A. Reynolds,
dated Jan. 3, 2007.

Estruch, J. J., G. W. Warren, M. A. Mullins, G. J. Nye, J. A. Craig, and
M. G. Koziel (1996). 	

	Vip3A, a novel Bacillus thuringiensis vegetative insecticidal protein
with a wide spectrum 	of activities against lepidopteran insects.  Proc.
Natl. Acad. Sci. 93:  5389 – 5394.

Negrotto, et al. (2000). The use of phosphomannose-isomerase as a
selectable marker to recover 			transgenic maize plants (Zea mays L. via
Agrobacterium transformation). Plant Cell 			Reports, 19: 798-803.

 An existing permanent exemption from the requirement of a tolerance is
established for PMI in all crops when used as a plant-incorporated
protectant inert ingredient (see 40 CFR 174.527).  

 The Cry1Ab PIP in Bt11 field corn has been registered as a PIP since
1996 [EPA Reg. No. 67979-1] and an 

exemption from the requirement of a tolerance has been established in
all crops (see 40 CFR 174.511).

 The mCry3A PIP in MIR604 field corn is registered as a PIP [EPA Reg.
No. 67979-5] and an exemption from the 

	requirement of a tolerance has been established in corn (see 40 CFR
174.505). 

 PAGE   

 PAGE   - 4 - 

*THIS REVIEW DOES NOT CONTAIN CONFIDENTIAL BUSINESS INFORMATION*