Plant Pesticide Inert Ingredient CP4 Enolpyruvylshikimate-3-D and the 

Genetic Material Necessary for Its Production in All Plants 

[Federal Register: August 2, 1996 (Volume 61, Number 150)]

[Rules and Regulations]               

[Page 40338-40340]

From the Federal Register Online via GPO Access [wais.access.gpo.gov]

[DOCID:fr02au96-14]

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[PP 5E4516/R2269; FRL-5391-2]

RIN 2070-AB78

 

Plant Pesticide Inert Ingredient CP4 Enolpyruvylshikimate-3-D and 

the Genetic Material Necessary for Its Production in All Plants

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 CP4 

Enolpyruvylshikimate-3-D (CP4 EPSPS) and the genetic material necessary 

for its production in all plants. A request for an exemption from the 

requirement of a tolerance was submitted by Monsanto Company 

(Monsanto). This

[[Page 40339]]

regulation eliminates the need to establish a maximum permissible level 

for residues of these plant pesticide inert ingredients in all plants.

EFFECTIVE DATE: Effective on August 2, 1996.

ADDRESSES: Written objections and hearing requests, identified by the 

document control number, [PP 5E4516/R2269], may be submitted to: 

Hearing Clerk (1900), Environmental Protection Agency, Rm. M3708, 401 M 

St., SW., Washington, DC 20460. 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. Fees accompanying objections shall be labeled ``Tolerance 

Petition Fees'' and forwarded: EPA Headquarters Accounting Operations 

Branch, OPP (Tolerance Fees), P.O. Box 360277M, Pittsburgh, PA 15251.

    An electronic copy of objections and hearing requests filed with 

the Hearing Clerk may be submitted to OPP by sending electronic mail 

(e-mail) to: opp-docket@epamail.epa.gov

    Copies of electronic objections and hearing requests must be 

submitted as an ASCII file avoiding the use of special characters and 

any form of encryption. Copies of electronic objections and hearing 

requests will also be accepted on disks in WordPerfect 5.1 file format 

or ASCII file format. All copies of electronic objections and hearing 

requests must be identified by the docket number [PP 5E4516/R2269] . No 

Confidential Business Information (CBI) should be submitted through e-

mail. Copies of electronic 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 (7501W), Office of 

Pesticide Programs, U. S. Environmental Protection Agency, 401 M St., 

SW., Washington, DC 20460. Office location and telephone number: 5th 

Floor CS, 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 October 25, 1995 (60 FR 54689)(FRL-4984-4), which 

announced that Monsanto Company, 700 Chesterfield Parkway North, St. 

Louis, MO 63198, had submitted a pesticide petition (PP) 5E4516 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 CP4 EPSPS 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. EPA has assigned these inert ingredients the name CP4 EPSPS 

and the genetic material necessary for its production in plants. 

``Genetic material necessary for its production'' means the genetic 

material which comprise (1) genetic material encoding the CP4 EPSPS and 

(2) its regulatory regions. ``Regulatory regions'' are the genetic 

material that control the expression of the genetic material encoding 

the CP4 EPSPS, 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 5E4516.

Toxicology Assessment

Product Characterization

     CP4 EPSPS protein produced in E. coli gave SDS-PAGE, western blot, 

N-terminal amino acid sequence and enzyme activity similar to the 

reference standard. The E. coli preparation lacked detectable 

glycosylation based on the staining reaction compared to transferritin 

and horseradish peroxidase positive controls.

    CP4 EPSPS protein as expressed in either E. coli or corn line 523-

06-1 were compared by SDS-PAGE, western blot, N-terminal amino acid 

sequence and specific enzyme activity against shikimate-3-phosphate and 

shown to have essentially equivalent characteristics save the specific 

activity which was lower in the plant preparation. The similarity of 

the CP4 EPSPS expressed in corn line 523-06-1 and MON80100 were shown 

to yield identical banding patterns indicating similar molecular weight 

and immunoreactivity.

    Western blot and enzymatic activity assays indicate that CP4 EPSPS 

is readily degraded in less than 2 minutes by incubation in simulated 

gastric fluid. In simulated intestinal fluid the enzyme activity and 

immunoreactivity lasts longer being still detectable at 10 minutes and 

undetectable by 270 minutes.

    CP4 EPSPS is an enzyme involved in aromatic amino acid synthesis. 

CP4 EPSPS is not closely related in amino acid homology to other 

described EPSPS enzymes. CP4 EPSPS is no more than 51.1% similar and 

26.0% identical to EPSPS in plants and 59.3% similar and 41.1% 

identical to EPSPS in other bacteria. The unique character of CP4 EPSPS 

is its ability to function in the presence of glyphosate which is a 

competitive inhibitor with PEP for the active site of other EPSPS
enzymes.

Toxicology

    In an acute oral toxicity test of bacterially-derived CP4 EPSPS 

protein, no test substance related deaths occurred at a dose of 572
mg/kg.

    The Agency expects that proteins with no significant amino acid 

homology to known mammalian protein toxins and which are readily 

inactivated by heat or mild acidic conditions and are readily degraded 

in an in vitro digestibility assay would have little likelihood for 

displaying oral toxicity.

    The data submitted and cited by Monsanto support the prediction 

that the CP4 EPSPS protein would be non-toxic to humans. 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 CP4 EPSPS is not considered acutely or chronically toxic. 

Adequate information was submitted to show that the test material 

derived from microbial cultures was biochemically similar to the CP4 

EPSPS as produced by the plant-pesticide in corn. Production of 

microbially produced protein was chosen in order to obtain sufficient 

material for testing.

    The genetic material necessary for the production of the CP4 EPSPS 

are the nucleic acids (DNA) which comprise (1) genetic material 

encoding the CP4 EPSPS and (2) its regulatory regions. ``Regulatory 

regions'' are the genetic material that control the expression of the 

genetic material encoding CP4 EPSPS, 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

[[Page 40340]]

consumption. These ubiquitous nucleic acids as they appear in the 

subject active ingredient have been adequately characterized by the 

applicant. Therefore, no mammalian toxicity is anticipated from dietary 

exposure to the genetic material necessary for the production of the 

CP4 EPSPS in any plant.

Conclusion

    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 the docket 

number [PP 5E4516/R2269] (including any comments and data submitted 

electronically). 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 22202.

    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 any copies of objections and hearing requests 

received electronically into printed, paper form as they are received 

and will place the paper copies in the official rule-making 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.

    Under Executive Order 12866 (58 FR 51735, October 4, 1993), this 

action is not a ``significant regulatory action'' and, since this 

action does not impose any information collection requirements as 

defined by the Paperwork Reduction Act, 44 U.S.C . 3501 et seq., it is 

not subject to review by the Office of Management and Budget. In 

addition, this action does not impose any enforceable duty or contain 

any unfunded mandate as described in the Unfunded Mandates Reform Act 

of 1995 (Pub. L. 104-4), or require prior consultation with State 

officials as specified by Executive Order 12875 (58 FR 58093, October 

28, 1993), or special considerations as required by Executive Order 

12898 (59 FR 7629, February 16, 1994).

    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 statement contianing the factual basis for this 

certification was published in the Federal Register of May 4, 1981 (46 

FR 24950).

    Under 5 U.S.C. 801(a)(1)(A) of the Administrative Procedure Act 

(APA) as amended by the Small Business Regulatory Enforcement Fairness 

Act of 1996 (Title II of Pub. L. 104-121, 110 Stat. 847), EPA submitted 

a report containing this rule and other required information to the 

U.S. Senate, the U.S. House of Representatives and the Comptroller 

General of the General Accounting Office prior to publication of the 

rule in today's Federal Register. This rule is not a ``major rule'' as 

defined by 5 U.S.C. 804(2) of the APA as amended.

List of Subjects in 40 CFR Part 180

    Environmental protection, Administrative practice and procedure, 

Agricultural commodities, Pesticides and pests, Reporting and 

recordkeeping requirements.

    Dated: July 30, 1996.

Daniel M. Barolo,

Director, Office of Pesticide Programs.

PART 180--[AMENDED]

    Therefore, 40 CFR Part 180 is amended as follows:

    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. 180.1174, to read as follows:

Sec. 180.1174   CP4 Enolpyruvylshikimate-3-phosphate (CP4 EPSPS) and 

the genetic material necessary for its production in all plants.

    CP4 Enolpyruvylshikimate-3-phosphate (CP4 EPSPS) and the genetic 

material necessary for its production in all plants are exempt from the 

requirement of a tolerance when used as plant pesticide inert 

ingredients in all raw agricultural commodities. ``Genetic material 

necessary for its production'' means the genetic material which 

comprise genetic material encoding the CP4 EPSPS and its regulatory 

regions. ``Regulatory regions'' are the genetic material that control 

the expression of the genetic material encoding the CP4 EPSPS, such as 

promoters, terminators, and enhancers.

[FR Doc. 96-19813 Filed 8-1-96; 8:45 am]

BILLING CODE 6560-50-F

