[Federal Register: October 27, 2004 (Volume 69, Number 207)]
[Notices]
[Page 62688-62692]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr27oc04-61]
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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: mendelsohn.mike@epa.gov.
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 opp-docket@epa.gov,
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