[Federal Register Volume 69, Number 178 (Wednesday, September 15, 2004)]
[Notices]
[Pages 55605-55608]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-20681]


-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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: [email protected].

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 [email protected], 
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