[Federal Register Volume 60, Number 158 (Wednesday, August 16, 1995)]
[Rules and Regulations]
[Pages 42450-42453]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-20010]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[PP 4E4410/R2160; FRL-4971-2]
RIN 2070-AB78
Plant Pesticide Inert Ingredient Phosphinothricin
Acetyltransferase (PAT) and the Genetic Material Necessary for Its
Production (Plasmid Vector pCIBP3064) in Corn; Tolerance Exemption
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This rule establishes an exemption from the requirement of a
tolerance for residues of the plant pesticide inert ingredient
phosphinothricin acetyltransferase and the genetic material necessary
for its production (plasmid vector pCIB3064) in corn. A request for an
exemption from the requirement of a tolerance was submitted by the
Ciba-Geigy Corp. (Ciba Seed). This regulation eliminates the need to
establish a maximum permissible level for residues of this plant
pesticide inert ingredient in the raw agricultural commodities of field
corn, sweet corn, and popcorn.
EFFECTIVE DATE: Effective on August 16, 1995.
ADDRESSES: Written objections and hearing requests, identified bythe
document control number [PP 4E4410/R2160], may be submitted to: Hearing
Clerk (1900), Environmental Protection Agency, Rm. M3708, 401 M St.,
SW.,
[[Page 42451]]
Washington, DC 20460. Fees accompanying objections shall be labeled
``tolerance Petition Fees'' and forwarded to: EPA Headquarters
Accounting Operations Branch, OPP (Tolerance Fees) P.O. Box 360277M,
Pittsburgh, PA 15251. A copy of any objections and hearing requests
filed with the Hearing Clerk should be identified by the document
control number and submitted 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 copy of objections and hearing requests to:
Rm. 1132, CM #2, 1921 Jefferson Davis Hwy., Arlington, VA 22202.
A copy of objections and hearing requests filed with the Hearing
Clerk may also be submitted electronically by sending electronic mail
(e-mail) to: opp-docket@epamail.epa.gov. Copies of objections and
hearing requests must be submitted as an ASCII file avoiding the use of
special characters and any form of encryption. Copies of objections and
hearing requests will also be accepted on disks in WordPerfect in 5.1
file format or ASCII file format. All copies of objections and hearing
requests in electronic form must be identified by the docket number,
[PP 4E4410/R2160]. No Confidential Business Information (CBI) should be
submitted through e-mail. Electronic copies of objections and hearing
requests on this rule may be filed online at many Federal Depository
Libraries. Additional information on electronic submissions can be
found below in this document.
FOR FURTHER INFORMATION CONTACT: By mail: Michael L. Mendelsohn,
Biopesticides and Pollution Prevention Division, Office of Pesticide
Programs, Environmental Protection Agency, 401 M St., SW., Washington,
DC 20460. Office location and telephone number: 5th Floor, CS #1, 2800
Crystal Drive, Arlington, VA 22202, Telephone No.: (703)-308-8715; e-
mail: mendelsohn.michael@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: EPA issued a notice, published in the
Federal Register of February 1, 1995 (60 FR 6093), which announced that
Ciba-Geigy Corp., P.O. Box 12257, Research Triangle Park, NC 27709-
2257, had submitted a pesticide petition (PP) 4E4410 to EPA requesting
that the Administrator, pursuant to section 408(d) of the Federal Food,
Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), establish an
exemption from the requirement of a tolerance for the plant pesticide
inert ingredient phosphinothricin acetyltransferase (PAT) as produced
in corn by the bar gene and its controlling sequences as found on
plasmid vector pCIB3064. EPA has assigned the inert ingredient of this
product the name phosphinothricin acetyltransferase and the genetic
material necessary for its production (plasmid vector pCIB3064) in
corn. ``Genetic material necessary for its production'' means the
genetic materials which comprise genetic material encoding the
phosphinothricin acetyltransferase (2) its regulatory regions.
``Regulatory regions'' are the genetic materials that control the
expression of the genetic material encoding the phosphinothricin
acetyltransferase, such as promoters, terminators, and enhancers.
There were no adverse comments or requests for referral to an
advisory committee received in response to the notice of filing of the
pesticide petition 4E4410.
Toxicology Assessment
EPA evaluated an acute oral toxicity study and an in vitro
digestibility study. In the acute mouse oral toxicity study, a 51% PAT
protein mixture was shown to have an LD50 greater than 5,050 mg/
kg. The Agency also expects that enzymes with no significant amino acid
homology to known protein toxins and which are readily inactivated by
heat or mild acidic conditions would also be readily degraded in an in
vitro digestibility assay and have little likelihood for displaying
oral toxicity. The PAT enzyme meets all the above criteria and, as
predicted, submitted data show that no toxicity results when high doses
of this protein are administered orally to laboratory rodents. When
proteins are toxic, they are known to act via acute mechanisms and at
very low dose levels [Sjobald, Roy D., et al., ``Toxicological
Considerations for Protein Components of Biological Pesticide
Products,'' Regulatory Toxicology and Pharmacology, 15, 3-9 (1992)].
Therefore, since no significant acute effects were observed, even at
relatively high dose levels, the PAT protein is not considered acutely
or chronicly toxic. The PAT acute oral toxicity study together with
data indicating that the PAT protein is rapidly degraded in the gastric
environment and is also readily denatured by heat or low pH are
sufficient to support a finding of no acute mammalian oral toxicity for
the PAT protein.
The genetic materials necessary for the production of the PAT
protein are the nucleic acids (DNA) which comprise the (1) genetic
material encoding the phosphinothricin acetyltransferase and (2) its
regulatory regions. ``Regulatory regions'' are the genetic materials
that control the expression of the genetic material encoding the
phosphinothricin acetyltransferase, such as promoters, terminators, and
enhancers. DNA is common to all forms of plant and animal life, and the
Agency knows of no instance where these nucleic acids have been
associated with toxic effects related to their consumption. These
ubiquitous nucleic acids as they appear in the subject inert ingredient
have been adequately characterized by the applicant. Therefore, no
mammalian toxicity is expected from dietary exposure to the genetic
material necessary for the production of the PAT protein in corn.
Allergenicity
Current scientific knowledge suggests that common food allergens
tend to be resistant to degradation by heat, acid, and proteases, are
glycosylated and are present at high concentrations in the food. Ciba-
Geigy has submitted data which indicates the PAT protein is rapidly
degraded in the gastric environment and is also readily denatured by
heat or low pH.
Submitted Data
1. Acute Oral Toxicity of Bacterially Produced PAT Protein. A white
powder (PAT-0195) containing 51% PAT enzyme by weight was obtained by
purification from an E. coli fermentation and dosed at 5,050 mg/kg to
mice. No treatment-related significant toxic effects were seen 14 days
after oral gavage of high levels of the purified PAT marker protein.
2. In-Vitro Digestibility of PAT Protein. The 22,000 M. W. PAT
enzyme is rapidly degraded in the presence of pepsin or low pH so that
it loses enzymatic activity and is not detected by SDS-PAGE. The enzyme
also loses activity if subject to temperatures over 35 degrees C. EPA
was relying on this study to demonstrate rapid degradation of the
protein.
3. Acute Oral Toxicity of Corn Leaf Protein Extracted from Bt/PAT
Corn. Application of this study to dietary risk assessment is not
possible because of extremely low doses administered, small test
populations, and the unexplained deaths occurring in both control and
treated groups. Therefore, EPA is not relying on this study to support
the tolerance exemption.
Residue Chemistry Data
Residue chemistry data were not required because of the lack of
mammalian toxicity of this active
[[Page 42452]]
ingredient. When proteins are toxic, they are known to act via acute
mechanisms and at very low dose levels [Sjobald, Roy D., et al.
``Toxicological Considerations for Protein Components of Biological
Pesticide Products,'' Regulatory Toxicology and Pharmacology, 15, 3-9
(1992)]. Therefore, since no significant acute effects were observed,
even at relatively high dose levels, the PAT protein is not considered
acutely or chronicly toxic. This is similar to the Agency position
regarding toxicity and the requirement of residue data for the
microbial Bacillus thuringiensis products. [See 40 CFR 158.740(b)] For
microbial products, further toxicity testing to verify the observed
effects and clarify the source of the effects (Tiers II & III) and
residue data are triggered by significant acute effects in studies such
as the mouse oral toxicity study.
The genetic material necessary for the production of the PAT
protein are the nucleic acids (DNA) which comprise (1) genetic material
encoding the phosphinothricin acetyltransferase and (2) its regulatory
regions. ``Regulatory regions'' are the genetic materials that control
the expression of the genetic material encoding the phosphinothricin
acetyltransferase, such as promoters, terminators, and enhancers. As
stated above, no mammalian toxicity is expected from dietary exposure
to the genetic material necessary for the production of the PAT protein
corn. Therefore, no residue data are required in order to grant an
exemption from the requirement of a tolerance for the plant pesticide
inert ingredient: phosphinothricin acetyltransferase (PAT) and the
genetic material necessary for its production (plasmid vector PCIB3064)
in corn.
Conclusions
Based on the information considered, the Agency concludes that
establishment of a tolerance is not necessary to protect the public
health. Therefore, the exemption from tolerance is established as set
forth below.
Any person adversely affected by this regulation may, within 30
days after publication of this document in the Federal Register, file
written objections to the regulation and may also request a hearing on
those objections. Objections and hearing requests must be filed with
the Hearing Clerk, at the address given above (40 CFR 178.20). A copy
of the objections and/or hearing requests filed with the Hearing Clerk
should be submitted to the OPP docket for this rulemaking. The
objections submitted must specify the provisions of the regulation
deemed objectionable and the grounds for the objections (40 CFR
178.25). Each objection must be accompanied by the fee prescribed by 40
CFR 180.33(i). If a hearing is requested, the objections must include a
statement of the factual issue(s) on which a hearing is requested, the
requestor's contentions on such issues, a summary of any evidence
relied upon by the objector as well as the other materials required by
40 CFR 178.27. A request for a hearing will be granted if the
Administrator determines that the material submitted shows the
following: There is genuine and substantial issue of fact; there is
reasonable possibility that available evidence identified by the
requestor would, if established, resolve one or more of such issues in
favor of the requestor, taking into account uncontested claims or facts
to the contrary; and resolution of the factual issue(s) in the manner
sought by the requestor would be adequate to justify the action
requested (40 CFR 178.32).
A record has been established for this rulemaking under docket
number [PP 4E4410/R2160] (including objections and hearing requests
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 a.m. to 4:30 p.m., Monday through Friday, excluding
legal holidays. The public record is located in Room 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.
Written objections and hearing requests, identified by the document
control number [PP 4E4410/R2160], may be submitted to the Hearing Clerk
(1900), Environmental Protection Agency, Rm. 3708, 401 M St., SW.,
Washington, DC 20460.
A copy of electronic objections and hearing requests filed with the
Hearing Clerk can be sent directly to EPA at:
opp-Docket@epamail.epa.gov
A copy of electronic objections and hearing requests filed with the
Hearing Clerk 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 any objections and hearing requests 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 objections and hearing requests submitted directly in
writing. The official rulemaking record is the paper record maintained
at the address in ``ADDRESSES'' at the beginning of this document.
Under Executive Order 12866 (58 FR 51735, October 4, 1993), the
Agency must determine whether the regulatory action is ``significant''
and therefore subject to all the requirements of the Executive Order
(i.e., Regulatory Impact Analysis, review by the Office of Management
and Budget (OMB)). Under section 3(f), the order defines
``significant'' as those actions likely to lead to a rule (1) having an
annual effect on the economy of $100 million or more, or adversely and
materially affecting a sector of the economy, productivity,
competition, jobs, the environment, public health or safety, or State,
local or tribal governments or communities (also known as
``economically significant''); (2) creating serious inconsistency or
otherwise interfering with an action taken or planned by another
agency; (3) materially altering the budgetary impacts of entitlement,
grants, user fees, or loan programs; or (4) raising novel legal or
policy issues arising out of legal mandates, the President's
priorities, or the principles set forth in this Executive Order.
Pursuant to the terms of this Executive Order, EPA has determined
that this rule is not ``significant'' and is therefore not subject to
OMB review.
Pursuant to the requirements of the Regulatory Flexibility Act
(Pub. L. 96-354, 94 Stat. 1164, 5 U.S.C. 601-612), the Administrator
has determined that regulations establishing new tolerances or raising
tolerance levels or establishing exemptions from tolerance requirements
do not have a significant economic impact on a substantial number of
small entities. A certification statement to this effect was published
in the Federal Register of May 4, 1981 (46 FR 24950).
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: August 7, 1995.
Penelope A. Fenner-Crisp,
Acting Director, Office of Pesticide Programs.
PART 180--[AMENDED]
Therefore, 40 CFR part 180 is amended as follows:
[[Page 42453]]
1. The authority citation for part 180 continues to read as
follows:
Authority: 21 U.S.C. 346a and 371.
2. In subpart D, by adding new Sec. 180.1151, to read as follows:
Sec. 180.1151 Phosphinothricin acetyltransferase and the genetic
material necessary for its production (plasmid vector pCIB3064) in
corn; exemption from the requirement of a tolerance.
Phosphinothricin acetyltransferase and the genetic material
necessary for its production (plasmid vector pCIB3064) in corn is
exempt from the requirement of a tolerance when used as a plant
pesticide inert ingredient in the raw agricultural commodities of field
corn, sweet corn, and popcorn. ``Genetic material necessary for its
production'' means the genetic materials which comprise genetic
material encoding the phosphinothricin acetyltransferase and its
regulatory regions. ``Regulatory regions'' are the genetic materials
that control the expression of the genetic material encoding the
phosphinothricin acetyltransferase, such as promoters, terminators, and
enhancers.
[FR Doc. 95-20010 Filed 8-15-95; 8:45 am]
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