[Federal Register Volume 62, Number 16 (Friday, January 24, 1997)]
[Notices]
[Pages 3682-3685]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-1754]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-660; FRL-5380-2]
DeKalb Genetics Corporation; Pesticide Tolerance Petitions
Filings
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice of filing.
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SUMMARY: This notice announces the filing of pesticide petitions
proposing regulations establishing exemptions from the requirement of a
tolerance for residues of the active ingredient plant-pesticide
Bacillus thuringiensis subsp. kurstaki CrylA(c) protein and the genetic
material necessary for the production of this protein in or on all raw
agricultural commodities and the inert ingredient plant-pesticide
phosphinothricin acetyltransferase protein and the genetic material
necessary for the production of this protein in or on all raw
agricultural commodities. This notice includes a summary of the
petition that was prepared by the petitioner, DeKalb Genetics
Corporation.
DATES: Comments, identified by the docket number PF-660, must be
received on or before February 24, 1997.
ADDRESSES: By mail, submit written comments to: Public Response and
Program Resources Branch, Field Operations Division (7506C), Office of
Pesticide Programs, Environmental Protection Agency, 401 M St., SW.,
Washington, DC 20460. In person, bring comments to: Rm. 1132, Crystal
Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA.
A record has been established for this notice document under docket
number PF-660 (including any comments and data submitted electronically
as described below). A public version of this record, including
printed, paper versions of electronic comments, which does not 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
public record is located in the Public Response and Program Resources
Branch, Field Operations Division (7506C), Office of Pesticide
Programs, Environmental Protection Agency, Rm. 1132, Crystal Mall #2,
1921 Jefferson Davis Highway, Arlington, VA.
Comments and data may also be submitted electronically by sending
electronic mail (e-mail) to: opp-docket@epamail.epa.gov or by
submitting disks. Electronic comments must be submitted either in ASCII
format (avoiding the use of special characters and any form of
encryption) or in WordPerfect in 5.1 file format. All comments and data
in electronic form must be identified by the docket number PF-660.
Electronic comments on this notice may be filed online at many Federal
Depository Libraries. The official record for this rulemaking, as well
as the public version described above, will be kept in paper form.
Accordingly, EPA will transfer all comments received electronically
into printed, paper form as they are received and will place the paper
copies in the official rulemaking record, which will also include all
comments submitted directly in writing.
Information submitted as a comment concerning this notice may be
claimed confidential by marking any part or all of that information as
``Confidential Business Information'' (CBI). Information so marked will
not be disclosed except in accordance with procedures set forth in 40
CFR part 2. No CBI should be submitted through e-mail. 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.
[[Page 3683]]
FOR FURTHER INFORMATION CONTACT: Mike Mendelsohn, Biopesticides and
Pollution Prevention Division (7501W), Office of Pesticide Programs,
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460.
Office location, telephone number, and e-mail address: 5th Floor, CS
B1, 2805 Jefferson Davis Hwy., Arlington, VA, 703-308-8715; e-mail:
mendelsohn.mike@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: EPA has received pesticide petitions (PP)
6E4710 and 6F4711 from DeKalb Genetics Corporation (Dekalb), 3100
Sycamore Road, DeKalb, IL 60115. The petitions propose, pursuant to
section 408 of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21
U.S.C. 346a, to amend 40 CFR part 180 to establish exemptions from the
requirement of a tolerance for the plant-pesticides Bacillus
thuringiensis subsp. kurstaki CrylA(c) protein and the genetic material
necessary for the production of this protein in or on all raw
agricultural commodities and phosphinothricin acetyltransferase protein
and the genetic material necessary for the production of this protein
in or on all raw agricultural commodities. EPA has determined that the
petition contains 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.
Dekalb has stated that analytical methods for the detection and
measurement of the CryIA(c) and PAT proteins are not needed since they
are petitioning for exemptions from the requirement of a tolerance on
the basis of mammalian safety.
As required by section 408(d) of the FFDCA, as recently amended by
the Food Quality Protection Act, Dekalb included in the petition a
summary of the petition and authorization for the summary to be
published in the Federal Register in a notice of receipt of the
petition. The summary represents the views of Dekalb; EPA, as mentioned
above, is in the process of evaluating the petition. As required by
section 408(d)(3) EPA is including the summary as a part of this notice
of filing. EPA may have made minor edits to the summary for the purpose
of clarity.
I. Petition Summary for PP 6F4711
This unit summarizes information cited by DeKalb to support the
proposed tolerance exemption for Bacillus thuringiensis subsp. kurstaki
CryIA(c) protein and the genetic material necessary for the production
of this protein in or on all raw agricultural commodities when used as
a plant-pesticide active ingredient.
A. Bacillus thuringiensis subsp. kurstaki CryIA(c) Protein Uses
Corn, Zea mays L., has been genetically engineered to be resistant
to Lepidopteran insect pests. Insect protection was accomplished by
insertion of the cryIA(c) gene from Bacillus thuringiensis subsp.
kurstaki which encodes a protein that is specifically insecticidal to
Lepidopteran insect larvae but Dekalb believes is safe to nontarget
organisms such as mammals, birds, fish, and nontarget insects. CryIA(c)
protein is used as a ``plant-pesticide'' in transgenic corn plants to
control Lepidopteran insects including European corn borer. CryIA(c)
corn will be deployed in situations where Lepidopteran insect control
is important.
B. Product Identity and Chemistry
Product analysis data demonstrated that microbially expressed and
purified CryIA(c) delta endotoxin used for mammalian toxicological
testing purposes is not significantly different than the delta
endotoxin expressed in the plant. The following assays were used to
determine the similarity of the microbially expressed and purified
CryIA(c) delta endotoxin and that produced in corn: SDS-PAGE, Western
blots, amino acid sequencing, testing for post translational
modification, and insect bioactivity. These assays demonstrated that
the truncated CryIA(c) delta endotoxin expressed in corn and the
tryptic core of the microbially-produced CryIA(c) endotoxin are
similar.
C. Mammalian Toxicological Profile
The CryIA(c) protein produced in transgenic corn is the tryptic
core of CryIA(c) found in nature and used in Bacillus thuringiensis
susp. kurstaki microbial formulations that have been registered with
the EPA and have been commercially available for over 30 years. To be
active against the target insect, CryIA(c) protein must be ingested. In
the insect gut, the protein binds to specific receptors in the insect
mid-gut, inserts into the membrane and forms ion-specific pores. These
events disrupt the digestive processes and cause the death of the
insect. There are no receptors for the protein delta endotoxins of
Bacillus thuringiensis subspecies on the surface of mammalian
intestinal cells; therefore humans are not susceptible to these
proteins.
The mammalian toxicological data submitted in support of the
exemption from the requirement for a tolerance include an acute oral
toxicity study with mice and a test for digestibility under simulated
gastric conditions. The results of these studies demonstrate that
CryIA(c) protein has an acute LD50 greater than 3,325 mg/kg. In
tests for digestibility in simulated gastric fluid, CryIA(c) protein
was found to degrade to below detectable levels within a few seconds
when exposed to full strength gastric fluid. When exposed to simulated
gastric fluid that had been diluted 100-fold, CryIA(c) protein degraded
to below detectable levels in five minutes. Given the rapid
digestibility of CryIA(c) delta endotoxin, no chronic effects are
expected. CryIA(c) delta endotoxin, or metabolites of the endotoxin are
not known to, or expected to have any effect on the immune or endocrine
systems. Proteins in general are not carcinogenic, therefore, no
carcinogenic risk is associated with the CryIA(c) protein.
Current scientific knowledge suggests that common food allergens
tend to be resistant to degradation by heat, acid, and proteases and
are glycosylated and present at high concentrations in food. CryIA(c)
delta endotoxin is rapidly degraded by simulated gastric fluid, is not
present as a major component in food, and is apparently nonglycosylated
or otherwise post-translationally modified when produced in plants.
Despite decades of widespread use of Bacillus thuringiensis as a
pesticide (it has been registered since 1961), there have been no
confirmed reports of immediate or delayed allergic reactions to the
delta endotoxins despite significant oral, dermal, and inhalation
exposure to microbial products containing the delta endotoxins.
The genetic material necessary for the production of Bacillus
thruringiensis CryIA(c) delta endotoxin are nucleic acids (DNA) which
comprise the genetic material encoding the CryIA(c) delta endotoxin and
the regulatory regions associated with the gene. Regulatory regions are
the genetic material that control the expression of the genetic
material encoding the CryIA(c) delta endotoxin, such as promoters,
terminators, introns, and enhancers. DNA is common to all forms of
plant and animal life, and there are no known instances of where
nucleic acids have been associated with toxic effects related to their
consumption. The nucleic acids introduced into CryIA(c) corn have been
characterized. No mammalian toxicity is expected from dietary exposure
to the genetic material necessary for the production of the
[[Page 3684]]
Bacillus thuringiensis CryIA(c) endotoxin in corn.
D. Aggregate Exposure
Exposure via dermal exposure or inhalation is unlikely given that
the delta endotoxin is contained in plant cells. Transfer of the
pesticide to drinking water is highly unlikely given that CryIA(c)
protein has been shown to degrade in senescing corn plants and Bt
proteins are known to rapidly degrade in the soil. Oral exposure, at
very low levels, may occur from ingestion of processed corn products
however the lack of mammalian toxicity, and the digestibility of the
protein have been demonstrated.
E. Cumulative Exposure
Consideration of a common mode of toxicity is not appropriate given
that there is no indication of mammalian toxicity of CryIA(c) protein
and no information that indicates that toxic effects would be
cumulative with any other compounds.
F. Safety Determination
1. U.S. population in general. The lack of acute toxicity and the
rapid digestibility of CryIA(c) delta endotoxin provides evidence for
the lack of toxicity and allergenicty and Dekalb believes support an
exemption from the requirement for a tolerance for Bacillus
thuringiensis subsp. kurstaki CryIA(c) protein. Bacillus thuringiensis
subsp. kurstaki delta endotoxins have been used in microbial
insecticide formulations that have been registered by the EPA and
commercially available since the early 1960s.
2. Infants and children. The use sites for CryIA(c) delta endotoxin
are all agricultural for control of Lepidopteran insects. Therefore,
nondietary exposure to infants and children is not expected. Dekalb
believes that the lack of toxicity of CryIA(c) delta endotoxin and
history of safe use of Bacillus thruringiensis subsp. kurstaki delta
endotoxins provides reasonable certainty that no harm will result to
infants and children from aggregate dietary exposure to residues of
CryIA(c).
G. Existing Tolerances or Tolerance Exemptions
An exemption from the requirement for a tolerance was granted by
the EPA for ``Plant-pesticide Bacillus thuringiensis CryIA(c) Delta-
Endotoxin and the Genetic Material Necessary for Its Production in
Cotton,'' Federal Register: September 15, 1995, (60 FR 47871; FRL-4976-
9).
II. Petition Summary for PP 6E4710
This unit summarizes information cited by DeKalb to support the
proposed tolerance exemption for phosphinothricin acetyltransferase
protein and the genetic material necessary for the production of this
protein in or on all raw agricultural commodities when used as a plant-
pesticide inert ingredient.
A. Phosphinothricin Acetyltransferase Protein Uses
Phosphinothricin acetyltransferase or PAT protein, is used as
``plant-pesticide inert ingredient'' in transgenic, insect protected
corn plants. PAT functions as a selectable marker and as well as a
source of resistance to glufosinate herbicides. PAT protein is encoded
by the bar gene, originally cloned from a common soil bacterium,
Streptomyces hygroscopicus. Insect protected corn will be deployed in
situations where Lepidopteran insect control is important.
B. Product Identity and Chemistry
Product analysis data demonstrated that microbially expressed and
purified PAT protein used for mammalian toxicological testing purposes
is not significantly different than the PAT protein expressed in the
plant. The following assays were used to determine the similarity of
the microbially expressed and purified PAT protein and that produced in
corn: SDS-PAGE,Western blots, amino acid sequencing and testing for
post translational modification. These assays demonstrated that the PAT
protein expressed in corn and PAT protein produced in and purified from
a microbial source are similar.
C. Mammalian Toxicological Profile
The PAT enzyme catalyzes the transfer of an acetyl group from
acetyl CoA to the amino group of phosphinothricin (also known as
glufosinate). The enzyme is highly substrate specific. Dekalb believes
it is therefore highly unlikely that PAT will acetylate any naturally
occurring compound in maize cells.
The mammalian toxicological data submitted in support of the
exemption from the requirement for a tolerance include an acute oral
toxicity study with mice and a test for digestibility under simulated
gastric conditions. The results of these studies demonstrate that PAT
protein has an acute LD50 greater than 2,500 mg/kg. In tests for
digestibility in simulated gastric fluid, PAT protein was found to
degrade to below detectable levels within 2 minutes when exposed to
full strength gastric fluid. When exposed to simulated gastric fluid
that had been diluted 100-fold, PAT protein degraded to below
detectable levels in 5 minutes. Given the rapid digestibility of PAT
protein, no chronic effects are expected. PAT protein or metabolites
protein are not known to, or expected to have any effect on the immune
or endocrine systems. Proteins in general are not carcinogenic,
therefore, no carcinogenic risk is associated with the PAT protein.
Current scientific knowledge suggests that common food allergens
tend to be resistant to degradation by heat, acid, and proteases and
are glycosylated and present at high concentrations in food. PAT
protein is rapidly degraded by simulated gastric fluid, is not present
as a major component in food, and is apparently nonglycosylated or
otherwise post-translationally modified when produced in plants.
The genetic material necessary for the production of PAT protein
are nucleic acids (DNA) which comprise the genetic material encoding
the PAT protein and the regulatory regions associated with the gene.
Regulatory regions are the genetic material that control the expression
of the genetic material encoding the PAT protein, such as promoters,
terminators, introns, and enhancers. DNA is common to all forms of
plant and animal life, and there are no known instances of where
nucleic acids have been associated with toxic effects related to their
consumption. The nucleic acids introduced into insect protected corn
have been characterized. No mammalian toxicity is expected from dietary
exposure to the genetic material necessary for the production of the
PAT protein in corn.
D. Aggregate Exposure
Exposure via dermal exposure or inhalation is unlikely given that
the PAT protein is contained in plant cells. Transfer of the pesticide
to drinking water is highly unlikely given that PAT protein is
undetectable in pollen, has been shown to degrade in senescing corn
plants. Oral exposure, at very low levels, may occur from ingestion of
processed corn products; however, Dekalb believes that the lack of
mammalian toxicity, and the digestibility of the protein have been
demonstrated.
E. Cumulative Exposure
Dekalb believes that consideration of a common mode of toxicity is
not appropriate given that there is no indication of mammalian toxicity
of PAT protein and no information that indicates that toxic effects
would be cumulative with any other compounds.
[[Page 3685]]
F. Safety Determination
1. U.S. population in general. Dekalb believes that the lack of
acute toxicity and the rapid digestibility of PAT protein provide
evidence for the lack of toxicity and allergenicty and support an
exemption from the requirement for a tolerance for PAT protein.
2. Infants and children. The use sites for insect protected corn
containing PAT protein are all agricultural for control of Lepidopteran
insects. Therefore, nondietary exposure to infants and children is not
expected. Dekalb believes that the lack of toxicity of PAT protein
provides reasonable certainty that no harm will result to infants and
children from aggregate dietary exposure to residues of PAT.
G. Existing Tolerances or Tolerance Exemptions
An exemption from the requirement for a tolerance was granted by
the EPA for ``Plant-pesticide Inert Ingredient Phosphinothricin
Acetyltransferase (PAT) and the Genetic Material Necessary for Its
Production (Plasmid Vector pCIBP3064) in Corn,'' Federal Register:
August 16, 1995, (60 FR 42450; FRL-4971-2).
III. Administrative Matters
EPA invites interested persons to submit comments on this notice of
filing. Comments must bear a notification indicating the document
control number [PF-660]. All written comments filed in response to this
petition will be available in the Public Response and Program Resources
Branch, at the address given above from 8:30 a.m. to 4 p.m., Monday
through Fridy, except legal holidays.
A record has been established for this notice under docket number
[PF-660] (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 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 public
record is located in Rm. 1132 of the Public Response and Program
Resources Branch, Field Operations Division (7506C), Office of
Pesticide Programs, Environmental Protection Agency, Crystal Mall #2,
1921 Jefferson Davis Highway, Arlington, VA.
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.
The official record for this rulemaking, as well as the public
version, as described above will be kept in paper form. Accordingly,
EPA will transfer all comments received electronically into printed,
paper form as they are received and will place the paper copies in the
official rulemaking record which will also include all comments
submitted directly in writing. The official rulemaking record is the
paper record maintained at the address in ``ADDRESSES'' at the
beginning of this document.
Authority: 21 U.S.C. 346a.
List of Subjects
Environmental protection, Agricultural commodities, Pesticides and
pests, Reporting and recordkeeping.
Dated: January 17, 1997.
Flora Chow,
Acting Director, Biopesticides and Pollution Prevention Division,
Office of Pesticide Programs.
[FR Doc. 97-1754 Filed 1-23-97; 8:45 am]
BILLING CODE 6560-50-F
