[Federal Register Volume 64, Number 66 (Wednesday, April 7, 1999)]
[Notices]
[Pages 16965-16967]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-8260]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-867; FRL-6069-8]


AgrEvo USA Company; Cry9C Plant-Pesticides; Notice of Filing of 
Pesticide Petition

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: This notice announces the initial filing of a pesticide 
petition proposing the amendment of a regulation to exempt from the 
requirement of a tolerance residues of plant-pesticides Bacillus 
thuringiensis subsp. tolworthi Cry9C and the genetic material necessary 
for the production of this protein in or on all raw agricultural 
commodities.

DATES: Comments, identified by the docket control number PF-867, must 
be received on or before May 7, 1999.
ADDRESSES: By mail submit written comments to: Information and Records 
Integrity Branch, Public Information and Services Divison (7502C), 
Office of Pesticides Programs, Environmental Protection Agency, 401 M 
St., SW., Washington, DC 20460. In person bring comments to: Rm. 119, 
CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
    Comments and data may also be submitted electronically by following 
the instructions under ``SUPPLEMENTARY INFORMATION.'' No confidential 
business information should be submitted through e-mail.
    Information submitted as a comment concerning this document may be 
claimed confidential by marking any part or all of that information as 
``Confidential Business Information'' (CBI). CBI should not be 
submitted through e-mail. Information marked as CBI will not be 
disclosed except in accordance with procedures set forth in 40 CFR part 
2. A copy of the comment that does not contain CBI must be submitted 
for inclusion in the public record. Information not marked confidential 
may be disclosed publicly by EPA without prior notice. All written 
comments will be available for public inspection in Rm. 119 at the 
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday, 
excluding legal holidays.

FOR FURTHER INFORMATION CONTACT: By mail: Mike Mendelsohn, Regulatory 
Action Leader, Biopesticides and Pollution Prevention Division, 
(7511C), Office of Pesticide Programs, Environmental Protection Agency, 
401 M St., SW., Washington, DC 20460. Office location and telephone 
number: Rm. 9th floor, Crystal Mall #2, 1921 Jefferson Davis Hwy., 
Arlington, VA. 22202, telephone (703) 308-8715; e-mail:mendelsohn.mike@
epamail.epa.gov.

SUPPLEMENTARY INFORMATION: 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 all raw agricultural 
commodities under section 408 of the Federal Food, Drug, and Comestic 
Act (FFDCA), 21 U.S.C. 346a. EPA has determined that this petition 
contain data or information regarding the elements set forth in section 
408(d)(2); however, EPA has not fully evaluated the sufficiency of the 
submitted data at this time or whether the data supports granting of 
the petition. Additional data may be needed before EPA rules on the 
petition.
    The official record for this notice, as well as the public version, 
has been established for this notice of filing under docket control 
number PF-867 (including comments and data submitted electronically as 
described below). A public version of this record, including printed, 
paper versions of electronic comments, which does not

[[Page 16966]]

include any information claimed as CBI, is available for inspection 
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal 
holidays. The official record is located at the address in 
``ADDRESSES'' at the beginning of this document.
    Electronic comments can be sent directly to EPA at:
    [email protected]


    Electronic comments must be submitted as an ASCII file avoiding the 
use of special characters and any form of encryption. Comment and data 
will also be accepted on disks in Wordperfect 5.1 file format or ASCII 
file format. All comments and data in electronic form must be 
identified by the docket control number (insert docket number) and 
appropriate petition number. Electronic comments on this notice may be 
filed online at many Federal Depository Libraries.
    Authority: 21 U.S.C. 346a.

List of Subjects

    Environmental protection, Agricultural commodities, Food additives, 
Feed additives, Pesticides and pests, Reporting and recordkeeping 
requirements.

    Dated: March 24, 1999.

Janet L. Andersen,

Director, Biopesticides and Pollution Prevention Division, Office of 
Pesticide Programs.

Petition Summary

    Below a summary of the pesticide petition is printed. The summary 
of the petition was prepared by 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.

AgrEvo USA Company

9F5050

    EPA has received a pesticide petition 9F5050 from AgrEvo USA 
Company, Little Centre One, 2711 Centerville Rd., Wilmington, DE 19808, 
proposing the amendment of 40 CFR 180.1192 to exempt from the 
requirement of a tolerance residues of the plant-pesticides Bacillus 
thuringiensis subspecies toliworthi Cry9C protein and the genetic 
material necessary for the production of this protein in or on all raw 
plant agricultural commodities under section 408 of the Federal Food, 
Drug, and Comestic Act (FFDCA), 21 U.S.C. 346a(d).
    Pursuant to section 408(d)(2)(A)(i) of the FFDCA, as amended, 
AgrEvo USA Company has submitted the following summary of information, 
data, and arguments in support of their pesticide petition. This 
summary was prepared by AgrEvo USA 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 plants have been protected from lepidopteran insect pests such 
as European corn borer [Ostrinia nubilalis (Huber)], by expressing a 
Cry9C protein. The Cry9C protein expressed by the corn plants 
corresponds to the insecticidal moiety of the Cry9C crystal protein of 
a Bacillus thuringiensis subsp. tolworthi strain. The Cry9C protein 
poses no foreseeable risks to non-target organisms, including mammals, 
birds and non-target insects. Transgenic corn plants, expressing Cry9C 
protein, represents an excellent addition to growers' options for 
insect control that reduces or eliminates the need for chemical inputs 
and fits well within an integrated pest management program.

B. Product Identity/Chemistry

    The cry9C gene, was isolated from the B.t. tolworthi strain, 
truncated and modified before it was stably inserted into corn plants. 
The tryptic core of the microbially produced Cry9C delta-endotoxin is 
similar to the Cry9C protein found in event CBH-351. The Cry9C protein 
was produced and purified from a bacterial host, for the purposes of 
mammalian toxicity studies. Product analysis that compared the Cry9C 
protein from the two sources included: SDS-PAGE, Western blots, N-
terminal amino acid sequencing, glycosylation tests (for possible post-
translational modifications) and insect bioassays.
    No analytical method is included since this petition requests an 
exemption from the requirement of a tolerance.

C. Mammalian Toxicological Profile

    Bacillus thuringiensis proteins have insecticidal properties and 
have been used commercially for more than 30 years. This long history 
of safe use is the primary reason that Bt proteins have been chosen as 
the basis for the first insecticidal plants produced by biotechnology. 
Bt mode-of-action can be divided into a series of critical steps: 
ingestion by the insect, specific binding to brush border membrane 
receptors, membrane insertion, and pore formation. Bt proteins do not 
bind or cause any other effects to mammalian gut membranes thereby 
displaying human safety properties. The Cry9C protein mode-of-action is 
apparently similar to that of the well known Cry1A proteins. Although 
Bt strains have been used for decades as sprayable microbial products, 
no confirmed cases of allergic reactions have been documented, despite 
dermal, oral and inhalation exposures. A reference to this is made by 
the EPA in a FR notice, dated August 16, 1995, (60 FR 42443)(FRL-4971-
3).
    In addition to the safe history of Bt proteins outlined above, 
several other studies were performed to provide evidence for mammalian 
safety of the Cry9C protein. An acute toxicological study was performed 
with mice, which demonstrated that the Cry9C protein had an 
LD50 >3,760 mg/kg. A test for in vitro digestibility under 
simulated gastric conditions showed that the Cry9C protein found in 
bacteria and the protein produced in plants was stable for 4 hours when 
exposed to simulated gastric juice. An amino acid sequence homology 
search performed using three different data banks (against 135,867 
sequences) only found homology to other related Bt proteins. All other 
proteins in the data bank have no major stretches of sequence homology, 
indicating that the sequence homology is not significant. Therefore, no 
homology with any known allergen or protein toxin could be 
demonstrated.
    The Cry9C protein or metabolites of the protein are not expected to 
interact with the immune system, the endocrine system or to have any 
carcinogenic activity since the protein sequence does not match any 
known allergens, hormones or since proteins, in general, are not known 
to be carcinogenic.
    All living organisms contain DNA and there are no examples of 
nucleic acids causing any toxicological effects from dietary 
consumption. The genetic material necessary for the production of the 
Cry9C protein in plants includes the genetic construct that encodes the 
Cry9C protein and all other necessary genetic elements for it's 
expression. These elements include: a promotor, polylinker sequences, 
leader sequences and terminators and none of which are expected to 
cause any toxicological effects.
    Taken together, the data supports the lack of mammalian 
toxicological effects

[[Page 16967]]

for the plant-pesticide Bacillus thuringiensis subsp. tolworthi Cry9C 
protein and the genetic material necessary for the production of this 
protein in or on all raw plant agricultural commodities.

D. Aggregate Exposure

    Since the Cry9C protein is expressed in plant tissues, dermal or 
inhalation will be negligible to non-existent. Drinking water is 
unlikely to be contaminated with Cry9C protein due to the rapid 
degradation of plant materials in the soil. Processed plant products 
may allow for low levels of exposure to the Cry9C protein, but the lack 
of mammalian toxicity and the lack of sequence homology to known toxins 
or allergens, has already been demonstrated.

E. Cumulative Exposure

    The unique mode-of-action of Bt proteins in general, coupled with 
the lack of mammalian toxicity for the Cry9C protein provides no basis 
for the expectation of cumulative exposure with other compounds.

F. Safety Determination

    Bt microbial pesticides containing Cry proteins have been applied 
for more than 30 years to food and feed crops consumed by the U.S. 
population. There have been no human safety problems attributed to Cry 
proteins. The extensive mammalian toxicity studies performed to support 
the safety of Bacillus thuringiensis - containing pesticides clearly 
demonstrate that the tested isolates are not toxic or pathogenic 
(McClintock, et al., 1995, Pestic. Sci. 45:95-105). The lack of 
mammalian toxicity or allergenic properties of the Cry9C protein 
provides support for our request of an exemption from the requirement 
of a tolerance set forth in this petition. Non-dietary exposure of 
infants, children or the US population in general, to the Cry9C protein 
expressed in plant materials, are not expected due to the uses of this 
product within agricultural settings.

G. Existing Tolerances

    An exemption from the requirement of a tolerance for residues of 
the insecticide, Bacillus thuringiensis subspecies tolworthi Cry9C 
protein and the genetic material necessary for its production in corn 
for feed use only; as well as in meat, poultry, milk, or eggs resulting 
from animals fed such feed was issued on May 22, 1998.

[FR Doc. 99-8260 Filed 4-6-99; 8:45 am]
BILLING CODE 6560-50-F