[Federal Register: December 10, 2003 (Volume 68, Number 237)]
[Notices]               
[Page 68911-68915]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr10de03-80]                         

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ENVIRONMENTAL PROTECTION AGENCY

[OPP-2003-0361; FRL-7336-2]

 
Bacillus thuringiensis Cry2Ab2 Protein and the Genetic Material 
Necessary for its Production in Cotton; Notice of Filing a Pesticide 
Petition to Amend a Tolerance Exemption 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, identified by docket ID number OPP-2003-0361, must be 
received on or before January 9, 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 are an 
agricultural producer, food manufacturer, or pesticide manufacturer. 
Potentially affected entities may include, but are not limited to:
    [sbull] Crop production (NAICS 111)
    [sbull] Animal production (NAICS 112)
    [sbull] Food manufacturing (NAICS 311)
    [sbull] Pesticide manufacturing (NAICS 32532)

[[Page 68912]]

    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-2003-0361. 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, 1921 Jefferson Davis Hwy., 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 on 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 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-2003-0361. 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-2003-0361. 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

[[Page 68913]]

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-2003-0361.
    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, 1921 Jefferson Davis Hwy., Arlington, VA, Attention: Docket 
ID number OPP-2003-0361. 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: November 19, 2003.
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 Monsanto Company 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.

Monsanto Company

PP 7F4888

    EPA has received a request (PP 7F4888) from Monsanto Company, 800 
N. Lindberg Blvd., St. Louis, MO 63167, 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 180, by removing the time limitation for 
the exemption from the requirement of a tolerance for the plant-
incorporated protectant Bacillus thuringiensis (Bt) Cry2Ab2 protein and 
the genetic material necessary for its production in cotton or on 
cotton. The tolerance exemption was originally requested under 
pesticide petition number (PF 7F4888).
    Pursuant to section 408(d)(2)(A)(i) of the FFDCA, as amended, 
Monsanto Company has submitted the following summary of information, 
data, and arguments in support of their pesticide petition. This 
summary was prepared by Monsanto Company 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

    Using plant molecular biology methods, Monsanto developed the 
Cry2Ab2 protein expressed in cotton plants. The production of Cry2Ab2 
protein provides highly effective and selective control of lepidopteran 
insect pests in cotton. Plants producing this protein are derived from 
plants transformed with the Cry2ab2 gene and the genetic material 
necessary for its expression in cotton. Cotton plants using the Cry2Ab2 
protein provide increased spectrum of activity over present products 
and in combination with existing technologies has the potential to 
increase the durability of the Bt proteins currently used for insect 
protection in cotton and increase the opportunities for integrated pest 
management.

B. Product Identity/Chemistry

    1. Identity of the pesticide and corresponding residues. The 
Cry2Ab2 protein is derived from Bacillus thuringiensis class of Cry2A 
proteins which are designated to have a greater than 95% sequence 
identity. Data characterizing the Cry2Ab2 protein used in cotton have 
been submitted to EPA.

[[Page 68914]]

Because it would be difficult, or impossible, to extract sufficient 
biologically active protein from plants to perform safety tests, 
Cry2Ab2 protein from bacteria was produced. Product analysis data show 
that the microbially expressed and purified Cry2Ab2 delta-enodtoxin is 
sufficiently similar to that expressed in the plant to be used for 
safety assessment purposes. Plant- and microbially produced Cry2Ab2 
delta-endotoxins were shown by these studies to have similar molecular 
weights and immunoreactivity (SDS-PAGE and Western blots), to lack 
detectable post-translational modification (glycosylation), to have 
identical amino acid sequences in the N-terminal region and to have 
similar results in bioassays against Heliothus vierscens and 
Heliocoverpa zea. The combined results of the above studies indicate a 
high probability that these two sources produce proteins that are 
essentially identical by available protein analytical assays.
    2. Magnitude of residue at the time of harvest and method used to 
determine the residue. The Cry2Ab2 protein is derived from Bacillus 
thuringiensis class of Cry2A proteins which are designated to have a 
greater than 95% sequence identity. Data characterizing the Cry2Ab2 
protein used in cotton have been submitted to EPA, because it would be 
difficult, or impossible, to extract sufficient biologically active 
protein from plants to perform safety tests, Cry2Ab2 protein from 
bacteria was produced. Product analysis data show that the microbially 
expressed and purified Cry2Ab2 delta-enodtoxin is sufficiently similar 
to that expressed in the plant to be used for safety assessment 
purposes. Plant- and microbially produced Cry2Ab2 delta-endotoxins were 
shown by these studies to have similar molecular weights and 
immunoreactivity (SDS-PAGE and Western blots), to lack detectable post-
translational modification (glycosylation), to have identical amino 
acid sequences in the N-terminal region and to have similar results in 
bioassays against Heliothus vierscens and Heliocoverpa zea. The 
combined results of the above studies indicate a high probability that 
these two sources produce proteins that are essentially identical by 
available protein analytical assays.
    3. A statement of why an analytical method for detecting and 
measuring the levels of the pesticide residue are not needed. A 
validated extraction and qualitative analytical method (ELISA) for the 
detection of Cry2Ab2 protein has been submitted to the Agency.

C. Mammalian Toxicological Profile

    The data submitted regarding potential health effects of Cry2Ab2 
include information on the characterization of the expressed protein in 
cotton. The acute oral toxicity data submitted support the 
determination that the Cry2Ab2 protein is non-toxic to humans. When 
proteins are toxic, they are known to act via acute mechanisms and at 
very low dose levels.
    The acute oral toxicity data submitted support the prediction that 
the Cry2Ab2 protein would be non-toxic to humans. Male and female mice 
(10 of each) were dosed with 67,359 and 1,450 milligrams/kilogram body 
weight (mg/kg bwt) of Cry2Ab2 protein. Outward clinical signs were 
observed and body weights recorded throughout the 14-day study. Gross 
necropsies performed at the end of the study indicated no findings of 
toxicity attributed to exposure to the test substance. No mortality or 
clinical signs attributed to the test substance were noted during the 
study. When proteins are toxic, they are known to act via acute 
mechanisms and at very lose dose levels (Sjoblad, Roy D., et al. 
``Toxicological Considerations for Protein Components of Biological 
Pesticide Products,'' Regulatory Toxicology and Pharmacolocy 15, 3-9 
(1992)). Therefore, because no effects were shown to be caused by the 
Cry2Ab2 proteins, even at relatively high dose levels, the Cry2Ab2 
protein is not considered to be toxic. Furthermore, amino acid sequence 
comparisons showed no similarity between Cry2Ab2 proteins and known 
toxic proteins available in public protein data bases.
    Data were submitted that demonstrate that the Cry2Ab2 delta-toxin 
is rapidly degraded by gastric fluid in vitro. In a solution of 
simulated gastric fluid (U.S. Pharmacopeia), complete degradation of 
detectable Cry2Ab2 protein occured within 15 seconds. Incubation in 
simulated intestinal fluid resulted in a 50 kDa protein digestion 
product. A comparison of amino acid sequences of know allergens 
uncovered no evidence of any homology with Cry2Ab2.
    Collectively, the submitted data on Cry2Ab2 protein, as well as the 
history of safe use with other plant-expressed and microbially produced 
Bacillus thuringiensis products, establishes the safety of the Cry2Ab2 
protein.
    The genetic material necessary for the production of the Cry2Ab2 
protein is nucleic acid (DNA) which is common to all forms of plant and 
animal life and there is no instance where these nucleic acids have 
been associated with toxic effects related to their consumption as a 
component of food.

D. Aggregate Exposure



    1. Dietary exposure--i. Food. Monsanto has considered available 
information on the aggregate exposure levels of consumers (and major 
identifiable subgroups of consumers) to the protein residue and to 
other related substances. These considerations include dietary exposure 
under the existing tolerance exemption and all other tolerances or 
exemptions in effect for the plant-incorporated protectant residue, and 
exposure from non-occupational sources. Oral exposure at very low 
levels may occur, but lack of mammalian toxicity and digestibility has 
been demonstrated.
    ii. Drinking water. Movement of the Cry2Ab2 protein to drinking 
water is highly unlikely given that Cry proteins are known to rapidly 
degrade in the soil. Oral exposure at very low levels may occur but 
lack of mammalian toxicity and the digestibility of this protein have 
been demonstrated.
    2. Non-dietary exposure. Exposure to Cry2Ab2 proteins via dermal 
exposure or inhalation is unlikely given that these proteins are 
contained in the plant and are not exuded and are not volatile. 
Therefore, worker and bystander exposure resulting from plant 
pesticides will be negligible and would be unlikely to add measurably 
to any worker or bystander exposure resulting from microbial or other 
Bacillus thuringiensis formulations.

E. Cumulative Exposure

    Available information on the cumulative effects of such residues 
and other substances that have a common mechanism of toxicity have been 
submitted. Because there is no indication of mammalian toxicity from 
this plant-incorporated protectant, there are no cumulative effects.

F. Safety Determination

    1. U.S. population. There is reasonable certainty that no harm will 
result from aggregate exposure to the U.S. population, including 
infants and children, to the Cry2Ab2 protein and the genetic material 
necessary for its production. This includes all anticipated dietary 
exposures and all other exposures for which there is reliable 
information. This conclusion is based on the low toxicity of the 
protein, lack of allergenicity, digestibility, and low dietary 
exposure.
    2. Infants and children. Nondietary exposure to infants and 
children is not anticipated due to the patterns of use for

[[Page 68915]]

this plant-incorporated protectant. Submitted data provide no evidence 
that Cry2Ab2 protein poses any adverse threshold effects that would 
warrant application of an additional safety factor for the protection 
of infants and children.

G. Effects on the Immune and Endocrine Systems

    The lack of Cry2Ab2 toxicity in high dose acute oral studies and 
its rapid degradation in a mammalian digestive system suggests minimal 
risk for adverse effects on the immune system. This pesticidally active 
ingredient is a protein, derived from sources that are not known to 
exert an influence on the endocrine system.

H. Existing Tolerances

    Bacillus thuringiensis Cry2Ab2 protein and the genetic material 
necessary for its production in corn and cotton is exempt from the 
requirement of a tolerance when used as a plant-pesticide in the food 
and feed commodities of field corn, sweet corn, popcorn, cottonseed, 
cotton oil, cotton meal, cotton hay, cotton hulls, cotton forage, and 
cotton gin byproducts (40 CFR 180.1215). Unless amended, this exemption 
will expire on May 1, 2004.

I. International Tolerances

    No Codex maximum residue levels have been established for this 
plant-incorporated protectant.
[FR Doc. E3-00490 Filed 12-9-03; 8:45 am]

BILLING CODE 6560-50-S