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.

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

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