\[Federal Register: September 28, 1994\]

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

\[OPP-300362; FRL-4912-5\]

RIN 2070-AB78

Neomycin Phosphotransferase II; Tolerance Exemption

AGENCY: Environmental Protection Agency (EPA)

ACTION: Final rule.

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SUMMARY: This document establishes an exemption from the requirement of

a tolerance for residues of neomycin phosphotransferase II (NPTII) and

the genetic material necessary for its production when used as a plant

pesticide inert ingredient. Monsanto Co. petitioned EPA for this

exemption.

EFFECTIVE DATE: This regulation becomes effective September 28, 1994.

ADDRESSES: Written objections and hearing requests, identified by the

document control number, \[OPP-300362\], 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 to: EPA Headquarters Accounting

Operations Branch, OPP (tolerance fees), P.O. Box 36027M, Pittsburgh,

PA 15251.

FOR FURTHER INFORMATION CONTACT: By mail: Phillip O. Hutton, Product

Manager (PM 18), Registration Division (7505C), Office of Pesticide

Programs, Environmental Protection Agency, 401 M St., SW., Washington,

DC\. Office location and telephone number: Rm. 213, CM #2, 1921

Jefferson Davis Hwy., Arlington, VA 22202, (703)-305-7690.

SUPPLEMENTARY INFORMATION: In the Federal Register of December 8, 1993

(58 FR 64582, 64583), EPA issued notices which announced that Monsanto

Co., 700 Chesterfield Parkway North, St. Louis, MO 63193, had submitted

a pesticide petition (PP 3F4273) to EPA proposing to amend 40 CFR part

180 to establish an exemption from the requirement of a tolerance for

neomycin phosphotransferase II (NPTII), and the genetic material

necessary to produce NPTII when produced in plants as a plant pesticide

inert ingredient. The Agency did not receive any comments on the

notices. Selectable markers such as NPTII are considered inert

ingredients by the Agency when they are introduced into a plant in

order to ensure or confirm the presence of a plant pesticide. The

genetic material necessary to produce NPTII (the NPTII gene) is also

considered part of the inert ingredient; therefore, the NPTII gene is

also addressed in this final rule.

Neomycin phosphotransferase II (NPTII) is uniquely different from

other types of inert ingredients because it is a selectable marker used

to identify plant cells early in the product development that had been

successfully transformed to express the active ingredient.

The data submitted in the petition and other relevant material have

been evaluated and deemed sufficient to support the tolerance. The

rationale for this decision is described below.

Assessment of Data

The Agency has evaluated the toxicology data, information on

product identity, equivalence of microbially and plant produced NPTII,

and other information provided by the petitioner. The information

showed that the plant and microbially produced protein are similar with

respect to the protein characteristics of amino acid sequence, enzyme

activity, electrophoretic mobility, lack of glycosylation, and specific

antibody recognition. These findings justified the use of microbial

protein in the toxicity studies. The registrant provided the following

studies: Acute Oral Toxicity of NPTII in Mice and an In Vitro Digestion

of the NPTII Protein. A single oral exposure dose of 5 g/kg NPTII

protein produced no adverse effects in mice. The In Vitro Digestion

study showed that the protein was rapidly degraded in simulated gastric

or intestinal digestive fluids to fragments that were no longer

recognized by specific antibodies to NPTII. These results suggest the

NPTII protein will not survive passage through the gastrointestinal

tract. Therefore, the Agency concluded that the information provided

was sufficient to assess the acute toxicity of NPTII when used as a

marker gene in transgenic plants expressing plant pesticides and to

justify an exemption from the requirement for a food tolerance for

residues of the inert. The Agency recognizes that alternative

information could be used to indicate the lack of mammalian toxicity

and to justify a tolerance exemption.

Since no toxicity was indicated, residue chemistry data were not

required. Residue data are necessary only if the submitted toxicity

studies indicate that additional toxicology data were needed. These

additional data were not needed. Therefore, no residue data are

required in order to grant an exemption from the requirement of a

tolerance for the plant pesticide inert ingredient neomycin

phosphotransferase II when used as a plant pesticide inert ingredient,

as expressed in plant cells.

The exemption from a tolerance for the genetic material which

encodes for production of NPTII is based on the fact that the nucleic

acids which form the genetic material are found in all foods and have

not, by themselves, been associated with toxic or pathogenic effects in

animals and humans. None of the constituents of nucleic acids are known

to be acute toxicants by themselves but, like proteins and other normal

constituents in food, may cause indirect, adverse metabolic effects if

consumed exclusively at high doses over a long period of time in the

absence of a normal diet. The NPTII gene will not occur at these high

amounts in plants. Thus, EPA does not believe there is a potential for

adverse health effects related to the consumption of plants containing

the NPTII gene.

Acceptable daily intake (ADI) and maximum permissible intake (MPI)

considerations are not relevant to this petition because the data/

information submitted demonstrate that this plant-pesticide inert

ingredient (NPTII) and the NPTII gene are not toxic to mammalian

species. No enforcement actions are expected based upon the level of

residue for NPTII and the genetic material necessary for its

production. Therefore, the requirement for an analytical method for

enforcement purposes is not applicable to this exemption.

Based on the above information and review of its use, EPA has found

that when used in accordance with good agricultural practice, this

ingredient is useful for the purpose for which the tolerance exemption

is sought. Based on the information considered, EPA concludes that a

tolerance is not necessary to protect the public health. Therefore, the

exemption from the requirement of a 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 and/or a request for a hearing with the Hearing

Clerk, at the address given above (40 CFR 178.20). A copy of the

objections and 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 each such issue, and a summary of any

evidence relied upon by the objector (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 a genuine and

substantial issue of fact; there is a 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).

The Office of Management and Budget has exempted this rule from the

requirements of section 2 of Executive Order 12866.

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 effect on a substantial number of

small entities. A certification statement to this effect was published

in the Federal Register of May 4, 1981 (49 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: September 19, 1994.

Stephen L. Johnson,

Director, Registration Division, Office of Pesticide Programs.

Therefore, 40 CFR part 180 is amended as follows:

PART 180\--\[AMENDED\]

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. 180.1134, to read as follows:

Sec. 180.1134 Neomycin phosphotransferase II and genetic material

necessary for its production; exemption from the requirement of a

tolerance.

The neomycin phosphotransferase II (NPTII) and the genetic material

necessary for the production of this protein are exempted from the

requirement of a tolerance in or on all raw agricultural commodities

when used as a plant-pesticide inert ingredient.

\[FR Doc. 94-23762 Filed 9-27-94; 8:45 am\]

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