Bacillus thuringiensis Cry3Bb1; Notice of Filing a Pesticide Petition to Establish a Tolerance Exemption 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, identified by docket identification (ID) number OPP-2003-0317, must be received on or before November 21, 2003.

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-2003-0317. 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 EPA's 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. 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 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-2003-0317. 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-2003-0317. 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-2003-0317.

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-2003-0317. 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

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.

I. Monsanto Company

PP 7F4888

EPA has received a pesticide petition request from Monsanto Company, 800 North Lindberg Blvd., St. Louis, Missouri 63167, proposing pursuant to section 408(d) of the 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 Cry3Bb1 protein and the genetic material necessary for its production in corn in or on field corn, sweet corn, and popcorn. 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

Corn has been genetically transformed to produce variants of the Bacillus thuringiensis protein Cry3Bb1. The production of Cry3Bb1 protein in root tissue protects corn from damage caused by corn rootworm larval feeding. Plants producing this protein are derived from transformation events that contain the insecticidal gene and the genetic material necessary for its expression in corn. Data developed with multiple Cry3Bb1 variants and corn transformation events indicate that the protein poses no foreseeable risks to nontarget organisms, including mammals, birds, fish, beneficial insects and earthworms. Cry3Bb1 corn is less toxic than all other currently registered rootworm control products. Cry3Bb1 corn provides growers with a highly efficacious product for controlling damage caused by corn rootworms that is compatible with integrated pest management practices.

B. Product Identity/Chemistry

1. Identity of the pesticide and corresponding residues. The gene encoding Cry3Bb1 protein was isolated from Bacillus thuringiensis subspecies kumamotoensis and modified before insertion into corn. Data characterizing the Cry3Bb1 variant produced in corn have been submitted to and reviewed by EPA. Safety studies were conducted with purified extracts of Cry3Bb1 produced in a heterologous bacterial fermentation system. Data submitted by Monsanto demonstrate that the plant- and bacterial-produced proteins are equivalent with respect to immunoreactivity, molecular weight, amino acid sequence, level of glycosylation, and insecticidal activity. Production of microbial Cry3Bb1 was needed to obtain sufficient quantities of the protein for use in safety testing.

2. Magnitude of residue at the time of harvest and method used to determine the residue. Cry3Bb1 residue data should not be required for a human health effects assessment because of the demonstrated lack of mammalian toxicity.

3. A statement of why an analytical method for detecting and measuring the levels of the pesticide residue are not needed. A validated method for extraction and direct enzyme linked immunosorbent assay (ELISA) analysis of Cry3Bb1 in corn grain has been submitted to the Agency.

C. Mammalian Toxicological Profile

Cry proteins have been used safely and effectively as pest control agents in microbial Bacillus thuringiensis formulations for more than 40 years. The numerous toxicology studies conducted with these microbial products show no significant adverse effects, and demonstrate that the products are practically nontoxic to mammals. An exemption from the requirement of a tolerance has been in place for these products since at least 1971 (40 CFR 180.1011).

Data have been submitted demonstrating the lack of mammalian toxicity at high levels of exposure to purified Cry3Bb1 proteins. These data demonstrate the safety of the proteins at levels well above maximum possible exposure levels that are reasonably anticipated in crops. This conclusion is consistent with the Agency position regarding toxicity and residue data requirements for the microbial Bacillus thuringiensis products from which this plant-incorporated protectant was derived (40 CFR 158.740(b)(2)(i)). For microbial products, further toxicity testing and residue data are only triggered by significant acute effects in studies such as the mouse oral toxicity study, to verify the observed effects and clarify the source of these effects (i.e., Tier II and Tier III testing).

Acute oral toxicity studies have been submitted for three Cry3Bb1 variants. These variants of the wild type Cry3Bb1 protein contain a small number of amino acid substitutions (four to seven) to enhance insecticidal activity against corn rootworm larvae. The acute oral toxicity data submitted support a prediction that Cry3Bb1 protein will be nontoxic to humans. Male and female mice (10 per sex per dose level) were dosed with 36, 396, or 3,780 milligrams/kilogram bodyweight (mg/kg bwt) of Cry3Bb1 protein for one variant. Mice were dosed with 39, 419, or 2,980 mg/kg bwt for a second Cry3Bb1 variant. Mice were dosed with 400, 1,100, or 3,200 mg/kg bwt of Cry3Bb1 for a third Cry3Bb1 variant. In one study, two animals in the high dose group died within a day of dosing. These animals both had signs of trauma probably due to dose administration (i.e., lung perforation or severe discoloration of lung, stomach, brain, and small intestinal tissue). No clinical signs were observed in the surviving animals and body weight gains were normal throughout the 14-day study for the remaining animals. Gross necropsies performed at the end of the study indicated no findings of toxicity attributed to exposure to the test substance in any of the three studies. No other mortality or clinical signs attributed to the test substance were noted in any of the studies.

When proteins are toxic, they are known to act via acute mechanisms and at very low levels (Sjoblad, R. et al. “Toxicological Considerations for Protein Components of Biological Pesticide Products.” Regulatory Toxicol. Pharmacol. 15:3-9, 1992). Since no acute effects were shown to be caused by Cry3Bb1 proteins, even at relatively high dose levels, they are not considered toxic. Furthermore, amino acid sequence comparisons between the Cry3Bb1 variants and known toxic proteins available in public databases showed no similarities.

Since Cry3Bb1 variants are proteins, the potential for allergic sensitivities was evaluated. Current scientific knowledge suggests that common food allergens are present at high concentrations in food, are resistant to pepsin digestion, may be resistant to acid or heat, and can be glycosylated. Data have been submitted demonstrating that the Cry3Bb1 proteins are rapidly degraded by gastric fluid in vitro. In a solution of simulated gastric fluid (pH 1.2 U.S. Pharmacopeia), complete degradation of detectable Cry3Bb1 protein occurred within 30 seconds. Insect bioassay data indicate that the protein loses insecticidal activity within 2 minutes of incubation in simulated gastric fluid. Incubation in simulated intestinal fluid resulted in a ~59 kDa protein digestion product. Cry3Bb1 protein produced in corn is not glycosylated and it is not detectable in grain following baking at elevated temperatures.

An analysis of amino acid sequences of known allergens uncovered no evidence of sequence homology with Cry3Bb1, even at the level of eight contiguous amino acid residues. The potential for Cry3Bb1 proteins to be food allergens is minimal. Regarding toxicity to the immune system, the acute oral toxicity data submitted support the prediction that Cry3Bb1 proteins will be nontoxic to humans.

The genetic material encoding the Cry3Bb1 proteins and the regulatory regions controlling expression of the nucleotide sequence encoding Cry3Bb1 proteins are nucleic acids deoxyribonucleic acid/ribonucleic acid ((DNA) and (RNA)). DNA and RNA occur in all forms of plant and animal life and there is no documented instance of nucleic acids being associated with toxic effects when consumed as a component of food. Data characterizing the genetic material necessary for the production of Cry3Bb1 in corn has been provided to the Agency. No mammalian toxicity is anticipated from dietary exposure to the genetic material necessary for production of the subject plant-incorporated protectant.

D. Aggregate Exposure

Data have been submitted with which to evaluate aggregate exposure levels for consumers to residues of the plant-incorporated protectant.

1. Dietary exposure. Cry3Bb1 is a plant-incorporated protectant in corn, thus dietary exposure is deemed to be the most relevant route for assessing human risk.

i. Food. Oral exposure, at very low levels, may occur from ingestion of processed corn products. However, a lack of mammalian toxicity and the rapid digestibility of the plant-incorporated protectant have been demonstrated.

ii. Drinking water. Oral exposure from ingestion of drinking water is unlikely because the protein is present at low levels within the plant and submitted studies demonstrate that Cry3Bb1 is rapidly degraded in soil.

2. Non-dietary exposure. Exposure via skin or inhalation is not likely since the plant-incorporated protectant is contained within plant cells, which essentially eliminates these exposure routes or reduces them to negligible. The use sites for Cry3Bb1 proteins are all agricultural for control of insects. Therefore, exposure via residential or lawn use to infants and children is not expected.

E. Cumulative Exposure

Since there is no indication of mammalian toxicity to the plant-incorporated protectant there will be no opportunity for cumulative toxic effects.

F. Safety Determination

1. U.S. population. Sufficient data have been submitted for the purpose of assessing health risk of Cry3Bb1 proteins and the genetic materials necessary for their production in raw agricultural commodities. The complete absence of toxicity in high dose acute oral studies, the lack of sequence homology with known protein toxins, rapid digestion in a gastric matrix, and minimal allergenicity potential provide a reasonable certainty of no harm for the U.S. general population potentially exposed to Cry3Bb1 proteins.

2. Infants and children. Nondietary exposure to infants and children is not anticipated due to the patterns of use for this plant-incorporated protectant. The submitted data provide no evidence of adverse threshold effects for Cry3Bb1 proteins that would warrant application of an additional safety factor for the protection of infants and children. Furthermore, the provisions for consumption patterns, special susceptibility, and cumulative effects do not apply.

G. Effects on the Immune and Endocrine Systems

The lack of Cry3Bb1 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 pesticidal active ingredient is a protein, derived from sources that are not known to exert an influence on the endocrine system.

H. Existing Tolerances

There is an existing time-limited tolerance exemption for Bacillus thuringiensis Cry3Bb1 protein and the genetic material necessary for its production in food and feed commodities of field corn, sweet corn and popcorn (40 CFR 180.1214). Unless amended, this exemption is scheduled to expire on May 1, 2004.

I. International Tolerances

No Codex maximum residue levels have been established for this plant-incorporated protectant at this time.