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Bacillus thuringiensis var. tolworthi, Cry9C Protein - Pesticide Petition Filing 3/99

[Federal Register: April 7, 1999 (Volume 64, Number 66)]
[Notices]
[Page 16965-16967]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr07ap99-69]
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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:
    opp-docket@epamail.epa.gov

    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