[Federal Register Volume 69, Number 207 (Wednesday, October 27, 2004)]
[Notices]
[Pages 62688-62692]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-23586]


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ENVIRONMENTAL PROTECTION AGENCY

[OPP-2004-0224; FRL-7370-1]


Modified Cry3A Protein mCry3A and the Genetic Material Necessary 
for its Production in Corn; 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.

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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, entified by docket identification (ID) number OPP-
2004-0224, must be received on or before November 26, 2004.

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:  Mike Mendelsohn, Biopesticides and 
Pollution Prevention Division (7511C), Office of Pesticide Programs, 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460-0001; telephone number: (703) 308-8715; e-mail 
address: [email protected].

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. 
Potentially affected 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 ID number OPP-2004-0224. 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, 1801 South Bell St., 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.1. 
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

[[Page 62689]]

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 e-mail 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-2004-0224. 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 [email protected], 
Attention: Docket ID number OPP-2004-0224. 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 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-2004-0224.
    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, 1801 South Bell St., Arlington, VA, Attention: Docket ID 
number OPP-2004-0224. 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: October 13, 2004.
Phil Hutton,
Acting Director, Biopesticides and Pollution Prevention Division, 
Office of Pesticide Programs.

Summary of Petition

     The petitioner's 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

[[Page 62690]]

the detection and measurement of the pesticide chemical residues or an 
explanation of why no such method is needed.

 Syngenta Seeds, Inc.

 PP 4F6838

     EPA has received a pesticide petition (PP 4F6838) from Syngenta 
Seeds, Inc., P.O. Box 12257, 3054 Cornwallis Road, Research Triangle 
Park, NC 27709-2257, proposing pursuant to section 408(d) of the 
Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to 
amend 40 CFR part 174 to establish an exemption from the requirement of 
a tolerance for the plant-incorporated protectant (modified Cry3A 
protein and the genetic material necessary for its production) in corn.
     Pursuant to section 408(d)(2)(A)(i) of the FFDCA, as amended, 
Syngenta Seeds, Inc. has submitted the following summary of 
information, data, and arguments in support of their pesticide 
petition. This summary was prepared by Syngenta Seeds, Inc. and EPA has 
not fully evaluated the merits of the pesticide petition. The summary 
may have been edited by EPA if the terminology used was unclear, the 
summary contained extraneous material, or the summary unintentionally 
made the reader conclude that the findings reflected EPA's position and 
not the position of the petitioner.

A. Product Name and Proposed Use Practices

     A modified Cry3A insect control protein and the genetic material 
necessary for its production in all corn is proposed for use as a 
plant-incorporated protectant active ingredient. Production of the 
modified Cry3A protein within corn plants confers resistance to damage 
caused by the western corn rootworm and northern corn rootworm, which 
are major corn pests in the United States. A permanent exemption from 
tolerances is being requested in conjunction with an application for 
commercial FIFRA section 3 registration of the active ingredient for 
use in corn.

B. Product Identity/Chemistry

    1. Identity of the pesticide and corresponding residues A modified 
Cry3A insect control protein is produced in transgenic corn plants 
derived from transformation Event MIR604. A cry3A gene from Bacillus 
thuringiensis subsp. tenebrionis was recreated synthetically to 
optimize for expression in corn. Additional changes in this corn-
optimized gene were made, such that the encoded modified Cry3A protein 
(mCry3A) has enhanced activity against larvae of the western corn 
rootworm (Diabrotica virgifera virgifera) and northern corn rootworm 
(D. longicornis barberi). Event MIR604-derived corn plants express the 
synthetic modified cry3A gene, introduced via transformation vector 
pZM26, and display resistance to these pests. The native Cry3A protein 
of B. thuringiensis subsp. tenebrionis is a ca. 73 kDa polypeptide of 
644 amino acids. By comparison, the mCry3A protein expressed in Event 
MIR604 corn is a ca. 67 kDa polypeptide of 598 amino acids. Its amino 
acid sequence corresponds to that of the native Cry3A protein, except 
that (1) its N-terminus corresponds to methionine-48 of the native 
protein and (2) a cathepsin G protease recognition site has been 
introduced into the protein, conferring markedly enhanced commercially 
exploitable activity toward western and northern corn rootworms. 
Residues of the mCry3A protein, and/or breakdown products thereof, are 
present in corn grain and other tissues of Event MIR604-derived plants.
    2. Magnitude of residue at the time of harvest and method used to 
determine theresidue. A determination of the magnitude of residue at 
harvest is not required for residues exempt from tolerances. However, 
the petitioner has provided data on the quantity of mCry3A protein 
measured in various plant parts. Average mCry3A levels in grain from 
Event MIR604-derived hybrid field corn plants were less than one part 
per million (ppm) on a dry-weight or fresh-weight basis, as measured by 
ELISA. Average mCry3A levels measured in chopped whole Event MIR604-
derived hybrid corn plants were less than or equal to ca. 20 ppm on a 
dry-weight basis and less than or equal to ca. 8 ppm on a fresh-weight 
basis.
    3. A statement of why an analytical method for detecting and 
measuring the levels of the pesticide residue are not needed. An 
analytical method is not required because this petition requests an 
exemption from tolerances. However, the petitioner has submitted an 
analytical method for detection of the mCry3A protein by ELISA.

C. Mammalian Toxicological Profile

     Syngenta Seeds has provided the results of a mammalian toxicology 
study, in vitro digestibility study, heat stability study and 
bioinformatics evaluations conducted on the mCry3A protein. These 
studies, summarized herein, demonstrate the lack of toxicity of the 
mCry3A protein following acute oral high-dose exposure to mice, rapid 
degradation of mCry3A upon exposure to simulated mammalian gastric 
fluid, instability of the mCry3A protein upon heating, and the lack of 
significant amino acid sequence homology of the mCry3A protein to 
proteins known to be mammalian toxins or human allergens.
     When proteins are toxic, they are known to act via acute 
mechanisms and at very low doses Sjoblad, R.D., J.T. McClintock and R. 
Engler (1992) Toxicological considerations for protein components of 
biological pesticide products. Regulatory Toxicol. Pharmacol. 15: 3-9]. 
Therefore, when a protein demonstrates no acute oral toxicity in high-
dose testing using a standard laboratory mammalian test species, this 
supports the determination that the protein will be non-toxic to humans 
and other mammals, and will not present a hazard under any realistic 
exposure scenario, including long-term exposures. Because it is not 
feasible to extract sufficient mCry3A protein from transformed plants 
for high-dose toxicology studies, mCry3A protein was produced in 
recombinant E. coli by over expressing the same modified cry3A gene 
that was introduced into Event MIR604 corn plants. Following 
purification from E. coli, dialysis and lyophilization, the resulting 
sample, designated test substance MCRY3A-0102, was estimated by ELISA 
to contain ca. 90.3% mCry3A protein by weight. Side-by-side comparisons 
of mCry3A in test substance MCRY3A-0102 with mCry3A extracted from 
Event MIR604-derived corn plants indicated that mCry3A from both 
sources is biologically active against the same target pest species, 
has the same apparent molecular weight by SDS-PAGE, immunoreacts with 
the same anti-Cry3A antibody, and is not apparently glycosylated post-
translation. Additionally, peptide mapping of ca. 60% of the mCry3A 
polypeptide by mass-spectral analysis confirmed the identity and 
intended amino sequence of mCry3A in test substance MCRY3A-0102. 
Nucleotide sequencing of the entire DNA insert in Event MIR604-derived 
plants also confirmed that the mCry3A protein produced in the plants 
has the exact intended amino acid sequence. These data justify the use 
of test substance MCRY3A-0102 in safety studies as a surrogate for 
mCry3A as produced in Event MIR604-derived plants.
     An acute toxicity study was conducted in mice according to EPA 
Test Guideline OPPTS 870.1100. Test substance MCRY3A-0102 was 
administered orally by gavage to 5 male and 5 female mice at a dose of 
2632 mg/

[[Page 62691]]

kg body weight, representing ca. 2,377 mg of pure mCry3A protein/kg 
body weight. A negative control group (5 males and 5 females) 
concurrently received the dosing vehicle alone, an aqueous suspension 
of 1% methylcellulose, at the same dosing volume used for the test 
substance mixture. No test substance-related mortalities or clinical 
signs of toxicity occurred during the 14-day study. One female mouse in 
the test group was euthanized the day following dosing due to adverse 
clinical signs resulting from a dosing injury (confirmed by post-mortem 
examination). At study termination, macroscopic and microscopic 
examination of all major organs of the surviving mice revealed no 
treatment-related abnormalities. Body weight, body weight gain and 
organ weights (brain, liver, kidneys and spleen) were comparable in the 
control and test groups. There was no evidence of toxicity. 
Accordingly, the LD50 value for MCRY3A-0102 in male and 
female mice is greater than 2,632 mg/kg body weight, and the 
LD50 value for pure mCry3A protein is greater than 2,377 mg/
kg body weight, the single dose tested.
     Extensive bioinformatics searches of public protein databases 
revealed that the mCry3A protein shows no significant amino acid 
homology to proteins known to be mammalian toxins or known or suspected 
to be human allergens. Additional information and testing indicate that 
the mCry3A protein does not have properties that would suggest it has 
the potential to become a food allergen. The source of native Cry3A 
protein (Bacillus thuringiensis) is not known to produce food 
allergens. Unlike allergenic proteins, which typically are present at 
1-80% of the total protein in an offending food, the average mCry3A 
concentration measured in raw grain derived from Event MIR604 corn 
represents less than 0.0001% of the total protein. (This calculation is 
based on corn grain containing 10% total protein by weight, and assumes 
less than 1 ppm mCry3A in the grain.) Additionally, due to degradation 
via food processing methods, mCry3A will not likely be present in 
processed food products, or will be present in only trace quantities. 
The mCry3A protein produced in transformed corn plants is not targeted 
to a cellular pathway for glycosylation, and shows no evidence of post-
translational glycosylation. Bioactivity of mCry3A is lost upon heating 
at 95 C for 30 minutes. Upon exposure to simulated mammalian gastric 
fluid containing pepsin, mCry3A rapidly degrades.
     The native Cry3A protein has had a history of safe use as a 
component of spore preparations of the microbial insecticide B. 
thuringiensis subsp. tenebrionis, as an encapsulated component of a 
microbial insecticide derived from B. thuringiensis subsp. San Diego, 
and as a plant-incorporated protectant in Bt potato.
     The genetic material occurring in the subject plant-incorporated 
protectant active ingredient has been adequately characterized. This 
genetic material (i.e., the nucleic acids DNA and RNA), including 
regulatory regions, necessary for the production of mCry3A in all corn 
will not present a dietary safety concern. ``Regulatory regions'' are 
the DNA sequences such as promoters, terminators, and enhancers that 
control the expression of the genetic material encoding the protein. 
Based on the ubiquitous occurrence and established safety of nucleic 
acids in the food supply, a tolerance exemption under the regulations 
has been established for residues of nucleic acids that are part of 
plant-incorporated protectants 40 CFR 174.475; 66 FR (139): 37817-
37830, July 19, 2001. Therefore, no mammalian toxicity is anticipated 
from dietary exposure to the genetic material necessary for the 
production of mCry3A protein in all corn.

D. Aggregate Exposure

    1. Dietary exposure--i. Food. Average mCry3A levels measured in 
grain from Event MIR604-derived hybrid field corn plants were less than 
one part per million (ppm) on a dry- or fresh-weight basis. Processed 
corn products or by-products used in food are unlikely to have 
measurable mCry3A protein, or will have only trace amounts. Oral 
exposure is not expected to result in adverse health effects, because 
of a demonstrated lack of toxicity to mammals and the rapid 
digestibility of the mCry3A protein. It is expected that any mCry3A 
protein consumed will be digested as conventional dietary protein.
    ii. Drinking water. Little to no exposure via drinking water is 
anticipated. Due to the demonstrated mammalian safety profile of 
mCry3A, such exposure would not present a risk.
    2. Non-dietary exposure. Non-dietary exposure is not anticipated, 
due to the proposed use pattern of the product. Exposure via dermal or 
inhalation routes is unlikely because the active ingredient is 
contained within plant cells. However, if exposure were to occur by 
non-dietary routes, no risk would be expected because the mCry3A 
protein is not toxic to mammals.

E. Cumulative Exposure

     Because there is no indication of mammalian toxicity of the mCry3A 
protein or the genetic material necessary for its production, it is 
reasonable to conclude, that there will be no cumulative effects for 
this active ingredient.

F. Safety Determination

    1. U.S. population. The lack of mammalian toxicity at high levels 
of exposure to the mCry3A protein demonstrates the safety of the 
product at levels well above possible maximum exposure levels 
anticipated via consumption of all food commodities produced from corn 
plants that produce mCry3A. Moreover, little to no human dietary 
exposure to mCry3A protein is expected to occur via transformed corn. 
Due to the digestibility and lack of toxicity of the mCry3A protein, 
and its very low potential to become an allergen in food, dietary 
exposure, if it occurred, is expected to not pose any harm for the U.S. 
population. No special safety provisions are applicable for consumption 
patterns or for any population sub-groups.
    2. Infants and children. Based on the mammalian safety profile of 
the active ingredient and the proposed use pattern, there is ample 
evidence to conclude a reasonable certainty of no harm to infants and 
children.

G. Effects on the Immune and Endocrine Systems

     The active ingredient is derived from sources that are not known 
to exert an influence on the endocrine or immune systems.

H. Existing Tolerances

     The registrant is not aware of any existing tolerances or 
tolerance exemptions for mCry3A protein and the genetic material 
necessary for its production as an active ingredient. The applicant has 
previously submitted a petition (File Symbol 4G6808) for temporary 
exemption from tolerances for the same active ingredient concurrently 
with an application for an Experimental Use Permit for use of the 
active ingredient in Event MIR604 corn. Exemptions from tolerances 
exist for use of the native form of Cry3A protein as a plant-
incorporated protectant in Bt potato (40 CFR 180.1147) and as a 
component of an encapsulated Bacillus thuringiensis microbial 
insecticide (40 CFR 180.1108).

[[Page 62692]]

I. International Tolerances

     No codex maximum residue levels exists for the plant-incorporated 
protectant modified Cry3A protein and the genetic material necessary 
for its production in corn.

[FR Doc. 04-23586 Filed 10-26-04; 8:45 am]
BILLING CODE 6560-50-S