[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: [email protected]. 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: [email protected].

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-D[email protected]


    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:

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    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]
BILLING CODE 6560-50-F