[Federal Register: September 15, 2004 (Volume 69, Number 178)]
[Notices]
[Page 55605-55608]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr15se04-38]
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ENVIRONMENTAL PROTECTION AGENCY
[OPP-2004-0275; FRL-7675-7]
Bacillus thuringiensis VIP3A Insect Control Protein and the
Genetic Material Necessary for its Production; Notice of Filing to a
Pesticide Petition to Amend the Exemption from the Requirement of 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-
2004-0275, must be received on or before October 15, 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: Leonard Cole, Biopesticides and
Pollution Prevention Division (7511C), Office of Pesticide Programs,
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460-0001; telephone number: (703) 305-5412; e-mail
address: cole.leonard@epa.gov.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be potentially affected by this action if you those persons
who are interested in agricultural biotechnology or may be required to
conduct testing of chemical substances under the Federal Food, Drug,
and Cosmetic Act (FFDCA), or the Federal Insecticide, Fungicide, and
Rodenticide Act (FIFRA) 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 identification (ID) number OPP-2004-0275. 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
[[Page 55606]]
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 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-2004-0275. 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-2004-0275. 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-2004-0275.
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-2004-0275. 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 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.
[[Page 55607]]
List of Subjects
Environmental protection, Agricultural commodities, Feed additives,
Food additives, Pesticides and pests, Reporting and recordkeeping
requirements.
Dated: August 24, 2004.
Janet L. Andersen,
Director, Biopesticides and Pollution Prevention Division, Office of
Pesticide Programs.
Summary of Petition
The petitioner 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 the detection and measurement
of the pesticide chemical residues or an explanation of why no such
method is needed.
Syngenta Seeds
PP 3G6547
EPA has received a pesticide petition, 3G6547, from Syngenta Seeds,
3054 Cornwallis Road, Research Triangle Park, NC 27709-2257 proposing,
pursuant to section 408(d) of FFDCA, 21 U.S.C. 346a(d) to amend 40 CFR
part 180 by amending an existing exemption from the requirement of a
tolerance, to include all VIP3A events. Bacillus thuringiensis VIP3A
insect control protein is expressed as a plant-incorporated protectant
in transgenic cotton plants to provide protection from key lepidopteran
pests including, but not limited to, Helicoverpa zea (cotton bollworm),
Heliothis virescens (tobacco budworm), and Pectinophora gossypiella
(pink bollworm).
Pursuant to section 408(d)(2)(A)(i) of the FFDCA, as amended,
Syngenta Seeds has submitted the following informmation, data, and
arguments in support of their pesticide petition. This summary was
prepared by Syngenta Seeds 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
VIP3A is one of a novel class of recently discovered insecticidal
proteins that occur naturally in Bacillus thuringiensis (Bt). The VIPs
(vegetative insecticidal proteins) are produced during vegetative
bacterial growth. Other than its demonstrated insecticidal activity,
VIP3A is not known to have any other biological or catalytic function.
Although VIP3A protein shares no homology with known Bt Cry proteins,
extensive testing has established that VIP3A is similarly very specific
in its activity, and has demonstrated toxicity only to the larvae of
certain lepidopteran species, including key pests of cotton. Further,
because VIP3A appears to target a different receptor than Cry proteins
in sensitive species, it represents a potentially useful tool in the
prevention or management of pest resistance to Cry proteins.
Upon commercial introduction, the use of transgenic VIP3A cotton
plants is expected to offer an important new option in lepidopteran
pest control and integrated pest management programs. Moreover, VIP3A
cotton will be an attractive, biologically based alternative to the use
of foliar insecticides. The use of VIP3A cotton plants is expected to
offer substantial environmental and worker safety benefits associated
with the reduced need for broad-spectrum insecticides. Additionally,
benefits to cotton growers will likely include greater profitability,
convenience and predictability in producing a high-yielding cotton
crop.
B. Product Identity/Chemistry
1. Identity of the pesticide and corresponding residues. The
VIPA(a) gene expressed in VIP3A cotton encodes a protein that is
identical to that encoded by the native VIP3A(a) gene originally
isolated from Bt strain AB88, with the exception of a single amino acid
difference at position 284; the native Bt gene encodes lysine, whereas
the synthetic gene in VIP3A cotton encodes glutamine at this position.
Research has demonstrated the specific insecticidal properties of VIP3A
to certain lepidopteran insects as well as its lack of effects on
nontarget organisms such as mammals, birds, fish, and beneficial
insects.
2. Magnitude of residue at the time of harvest and method used to
determine the residue. A determination of the magnitude of residue at
harvest is not required for residues exempt from tolerances.
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 a
validated analytical method for detection of the VIP3A protein in
cottonseed.
C. Mammalian Toxicological Profile
The VIP3A(a) gene expressed in cotton is very similar (ca. 99%
homology) to VIP3A or VIP3A-like genes that appear to occur commonly in
Bt strains from a variety of sources. It has been determined that the
VIP3A protein demonstrates insect-specific toxicity and must be
ingested and processed by a sensitive lepidopteran larval insect to be
active. Once in the insect gut, the activated VIP3A protein binds to
specific receptors (different from those bound by Bt Cry1A proteins),
inserts into the gut membrane and forms ion-specific pores. The
resulting ion imbalances cause death of the insect. However, the mode
of action of VIP3A in sensitive insects is not relevant to humans and
most other organisms, because they lack gut receptors that recognize
the VIP3A protein. The mammalian safety of VIP3A has been confirmed in
numerous studies conducted in laboratory animals, which are traditional
experimental surrogates for humans. These studies, summarized herein,
demonstrate the lack of toxicity of the VIP3A protein following high-
dose acute oral exposures to mice, rapid degradation of VIP3A upon
exposure to simulated mammalian gastric fluid; instability of the VIP3A
protein upon heating; and the lack of amino acid sequence similarity of
the VIP3A protein to proteins known to be mammalian toxins or human
allergens. It can be concluded from these studies that the VIP3A
protein will be non-toxic to humans.
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.
Studies conducted to assess the mammalian safety of VIP3A protein
have demonstrated no toxicity. Four acute oral toxicity studies in mice
have been completed. Three of the VIP3A test substances used were
produced via microbial expression systems and one was prepared by
extracting protein from
[[Page 55608]]
leaves of VIP3A-expressing corn plants. Two of the test substances
contained the exact same VIP3A protein as is expressed in VIP3A cotton;
the remaining two test substances contained VIP3A protein that differed
from the VIP3A protein expressed in cotton by one or two amino acids
(out of a total of 789). At maximum dosage the microbially expressed
test substance was administered at a level of 5,000 milligrams/kilogram
(mg/kg) body weight, representing 3,675 mg of pure VIP3A protein per kg
body weight. Because toxicity was not observed at this dose, it can be
concluded that the lethal dose (LD)50 for pure VIP3A protein
is >3,675 mg/kg body weight. The VIP3A protein in both the microbial
and plant-derived test substances were determined to be substantially
equivalent to VIP3A produced in cotton plants, as measured by
biological activity, protein size, immunoreactivity, mass spectral
analysis of amino acid sequence, and apparent lack of post-
translational modifications. Nucleotide sequencing of the entire DNA
insert in VIP3A cotton plants also confirmed that the VIP3A protein
encoded therein has the intended amino acid sequence. These data
justify the use of VIP3A test substances as surrogates for VIP3A
protein as produced in transgenic cotton plants.
The amino acid sequence of VIP3A is not homologous to that of any
known or putative allergens described in public databases. The VIP3A
protein is not derived from a known source of allergens and does not
display characteristics commonly associated with allergens, including
glycosylation or stability to heat and food processing. Additionally,
VIP3A is susceptible to gastric digestion by pepsin and did not provoke
an allergic response in an experimental atopic dog model of human food
allergy.
VIP3A or VIP3A-like proteins appear to be present in multiple
commercial formulations of Bacillus thuringiensis (Bt) microbial
insecticides at concentrations estimated to be ca. 0.4 - 32 ppm. This
conclusion is based on the presence of proteins of the appropriate
molecular weight and immunoreactivity (by SDS-PAGE and western blot),
and quantitation by ELISA. Therefore, it is conceivable that small
quantities of VIP3A protein are present in the food supply because
VIP3A (or a very similar protein, based on size and immunoreactivity)
appears to be present in currently registered insecticide products used
on food crops, including fresh market produce. These commercial Bt
products are all exempt from food and feed tolerances.
The genetic material (i.e., the nucleic acids DNA and RNA),
including regulatory regions, necessary for the production of VIP3A
protein in cotton 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 has been established for residues of nucleic acids that are
part of plant-incorporated protectants (40 CFR part 174.475).
Therefore, no toxicity is anticipated from dietary exposure to the
genetic material necessary for the production of VIP3A protein in
cotton.
D. Aggregate Exposure
1. Dietary exposure--i. Food. Food products derived from cotton
(refined cottonseed oil and cellulose ``linters'' fiber) are highly
processed and are essentially devoid of any proteins. Little or no
human dietary exposure to VIP3A protein is expected to occur via VIP3A
cotton. However, even if exposure were to occur by this route, no risk
would be expected because the VIP3A protein is not toxic to mammals.
ii.Drinking water. No exposure to VIP3A and the genetic material
necessary for its production in cotton via drinking water is expected.
The proteins are incorporated into the plant and will not be available.
However, if exposure were to occur by this route, no risk would be
expected because the VIP3A protein is not toxic to mammals.
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 plant-incorporated protectant
is contained within plant cells. However, if exposure were to occur by
non-dietary routes, no risk would be expected because the VIP3A protein
is not toxic to mammals.
E. Cumulative Exposure
Because there is no indication of mammalian toxicity to the VIP3A
protein, it is reasonable to conclude that there are no cumulative
effects for this plant-incorporated protectant.
F. Safety Determination
1.U.S. population. The lack of mammalian toxicity at high levels of
exposure to the VIP3A protein demonstrates the safety of the product at
levels well above possible maximum exposure levels anticipated via
consumption of processed food products produced from VIP3A cotton.
Moreover, little to no human dietary exposure to VIP3A protein is
expected to occur via VIP3A cotton. Due to the digestibility and lack
of toxicity of the VIP3A protein and its very low potential for
allergenicity, dietary exposure is not anticipated to 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. Thus, there are no threshold effects of concern and,
consequently, there is no need to apply an additional margin of safety.
G. Effects on the Immune and Endocrine Systems
The safety data submitted show no adverse effects in mammals, even
at very high dose levels, and support the prediction that the VIP3A
protein would be non-toxic to humans. Therefore no effects on the
immune or endocrine systems are predicted. Further, the VIP3A protein
is derived from a source that is not known to exert an influence on the
endocrine system.
H. Existing Tolerances
A time-limited exemption from the requirement of a tolerance was
granted by EPA in the Federal Register of March 31, 2004 (69 FR 16806)
(FRL-7350-8) for the Bacillus thuringiensis VIP3A protein and the
genetic material necessary for its production in cotton event COT102
(40 CFR 180.1247). The VIP3A protein expressed in other cotton events
(such as COT202 and COT203) is equivalent, and likely identical, to
that protein expressed in event COT102.
I. International Tolerances
There are no existing international tolerances or exemptions from
tolerance for the Bacillus thuringiensis VIP3A protein and the genetic
material necessary for its production.
[FR Doc. 04-20681 Filed 9-14-04; 8:45 am]
BILLING CODE 6560-50-S