Phosphinothricin Acetyltransferase and the Genetic Material Necessary
for

Its Production in All Plants; Exemption From the Requirement of a

Tolerance On All Raw Agricultural Commodities

\[Federal Register: April 11, 1997 (Volume 62, Number 70)\]

\[Rules and Regulations\]

\[Page 17717-17720\]

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

\[DOCID:fr11ap97_dat-11\]

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

\[OPP-300463; FRL-5597-3\]

RIN No. 2070-AB78

Phosphinothricin Acetyltransferase and the Genetic Material

Necessary for Its Production in All Plants; Exemption From the

Requirement of a Tolerance On All Raw Agricultural Commodities

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 the plant-pesticide inert ingredients

Phosphinothricin Acetyltransferase (PAT) and the genetic material

necessary for its production in all plants when used as plant-

pesticides in or on all raw agricultural commodities (RACs). Dekalb

Genetics Corporation submitted a petition to EPA under the Federal

Food, Drug, and Cosmetic Act (FFDCA) as amended by the Food Quality

Protection Act of l996 (FQPA) requesting the exemption from the

requirement of a tolerance. This regulation eliminates the need to

establish a maximum permissible level for residues of this plant-

pesticides in or on all RACS.

EFFECTIVE DATE: This regulation becomes effective on April 11, 1997.

ADDRESSES: Written objections and hearing requests, identified by the

docket control number, \[OPP-300463\], may be submitted to: Hearing
Clerk

(1900), Environmental Protection Agency, Rm. M3708, 401 M St., SW.,

Washington, DC 20460. Fees accompanying objections and hearing requests

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

docket 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 Highway., Arlington,

VA. A copy of objections and hearing requests filed with the Hearing

Clerk may also be submitted electronically to the OPP 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 control number \[OPP-300463\]. 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 in Unit VIII. of

this preamble.

FOR FURTHER INFORMATION CONTACT: By mail: Mike Mendelsohn,

Biopesticides and Pollution Prevention Division, Office of Pesticide

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

Washington, DC 20460. Office location, telephone number, and e-mail

address: 5th Floor CS, 2800 Crystal Drive, Arlington, VA 22202, (703)-

308-8715); email: mendelsohn.mike@epamail.epa.gov.

SUPPLEMENTARY INFORMATION: In the Federal Register of January 24, 1996

(62 FR 3682)(FRL-5380-2), EPA issued a notice pursuant to section

408(d) of FFDCA, 21 U.S.C. 346a(d) announcing the filing of a pesticide

petition for an exemption from the requirement for a tolerance by

Dekalb Genetics Corporation (Dekalb), 3100 Sycamore Road, Dekalb, IL

60115\. The notice contained a summary of the petition prepared by the

petitioner and this summary contained conclusions and arguments to

support its conclusion that the petition complied with the FQPA (Pub.

L. 104-170). The petition requested that an exemption from the

requirement of a tolerance be established for the plant-pesticides PAT

and the genetic material necessary for its production in plants in or

on all raw agricultural commodities (RACS). There were no comments or

requests for referral to an advisory committee received in response to

the notice of filing. The data submitted in the petition and other

relevant material have been evaluated. The toxicology and other data

listed below were considered in support of this exemption from the

requirement of a tolerance.

I. Toxicological Profile

The data submitted regarding potential health effects of PAT

include information on the characterization of the expressed protein in

corn, the acute oral toxicity of PAT, and in vitro digestibility

studies of the protein. The results of these studies were determined

applicable to evaluate human risk and the validity, completeness, and

reliability of the available data from the studies were considered.

The acute oral toxicity test of bacterially-derived PAT protein

showed no test substance related deaths at a dose of 2,500 milligrams

per kilogram (mg/kg). Residue chemistry data were not required for a

human health effects assessment of the subject plant-pesticide inert

ingredients because of the lack of mammalian toxicity. Both (1)

available information concerning the dietary

\[\[Page 17718\]\]

consumption patterns of consumers (and major identifiable subgroups of

consumers including infants and children) and (2) safety factors which,

in the opinion of experts qualified by scientific training and

experience to evaluate the safety of food additives, are generally

recognized as appropriate for the use of animal experimentation data

were not evaluated because the lack of mammalian toxicity at high

levels of exposure demonstrate the safety of the product at levels

above possible maximum exposure levels. This is similar to the Agency

position regarding toxicity and the requirement of residue data for the

microbial Bacillus thuringiensis. \[See 40 CFR 158.740(b).\] For

microbial products, further toxicity testing to verify the observed

effects and clarify the source of the effects (Tiers II and III) and

residue data are triggered by significant acute effects in studies such

as the mouse oral toxicity study.

The acute oral toxicity data submitted support the prediction that

the PAT 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

\[Sjoblad, Roy D., et al. \`\`Toxicological Considerations for Protein

Components of Biological Pesticide Products,\'\' Regulatory Toxicology

and Pharmacology 15, 3-9 (1992)\]. Therefore, since no effects were

shown to be caused by the plant-pesticides, even at relatively high

dose levels, the PAT delta-endotoxin protein is not considered toxic.

Adequate information was submitted to show that the PAT test

material derived from microbial cultures was biochemically and,

functionally similar to the proteins produced by the plant-pesticide

inert ingredient in corn. Production of microbially produced protein

was chosen in order to obtain sufficient material for testing. In

addition, the in vitro digestibility studies indicate the proteins

would be rapidly degraded following ingestion.

The genetic material necessary for the production of the plant-

pesticides active and inert ingredients are the nucleic acids (DNA)

which comprise (1) genetic material encoding these proteins and (2)

their regulatory regions. \`\`Regulatory regions\'\' are the genetic

material that control the expression of the genetic material encoding

the proteins, 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 as a component of food. These

ubiquitous nucleic acids as they appear in the subject plant-pesticide

inert ingredient has 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 subject

active and inert plant pesticidal ingredients.

II\. Sensitivity of Subgroups

The Agency has considered available information on the variability

of the sensitivities of major identifiable subgroups of consumers

including infants and children and the physiological differences

between infants and children and adults and effects of in utero

exposure to the plant-pesticides. Since PAT is a protein, allergenic

sensitivities were considered. 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. Data has been submitted which demonstrate

that the PAT protein is rapidly degraded by gastric fluid in vitro and

is non-glycosylated. Thus, the potential for the PAT protein to be a

food allergen is minimal.

III\. Cumulative Effects

The Agency has considered available information on the cumulative

effects of such residues and other substances that have a common mode

of toxicity. These considerations included the cumulative effects on

infants and children of such residues and other substances with a

common mechanism of toxicity. Because there is no indication of

mammalian toxicity to these plant-pesticides, there are no cumulative

effects.

IV\. Aggregate Exposures

The Agency has considered available information on the aggregate

exposure levels of consumers (and major identifiable subgroups of

consumers) to the pesticide chemical residue and to other related

substances. These considerations include dietary exposure under the

tolerance exemption and all other tolerances or exemptions in effect

for the plant-pesticides chemical residue, and exposure from non-

occupational sources. Exposure via the skin or inhalation is not likely

since the plant-pesticides are contained within plant cells which

essentially eliminates these exposure routes or reduces these exposure

routes to negligible. Oral exposure, at very low levels, may occur from

ingestion of processed corn products and drinking water. However a lack

of mammalian toxicity and the digestibility of the plant-pesticides has

been demonstrated. At present, the use sites for PAT are all

agricultural. Therefore, exposure via residential or lawn use to

infants and children is not expected. Even if negligible exposure

should occur, the Agency concludes that such exposure would present no

risk due to the lack of toxicity.

FFDCA section 408 provides that EPA shall apply an additional

tenfold margin of exposure (safety) for infants and children in the

case of threshold effects to account for pre- and post-natal toxicity

and the completeness of the database unless EPA determines that a

different margin of exposure (safety) will be safe for infants and

children. In this instance EPA believes there is reliable data to

support the conclusion that the plant-pesticides are not toxic to

mammals, including infants and children, and thus there are no

threshold effects of concern. As a result, the provision requiring an

additional margin of exposure does not apply.

V. Endocrine Effects

EPA does not have any information regarding endocrine effects for

these kinds of pesticides at this time. The Agency is not requiring

information on the endocrine effects of these plant-pesticides at this

time; and Congress allowed 3 years after August 3, 1996, for the Agency

to implement a screening and testing program with respect to endocrine

effects.

VI\. Conclusion

There is a reasonable certainty that no harm will result from

aggregate exposure to the U. S. population, including infants and

children, to the PAT protein and the genetic material necessary for its

production. This includes all anticipated dietary exposures and all

other exposures for which there is reliable information. The Agency has

arrived at this conclusion because, as discussed above, no toxicity to

mammals has been observed for the plant-pesticides. As a result, EPA

establishes an exemption from tolerance requirements pursuant to FFDCA

section 408(j)(3) for PAT and the genetic material necessary for its

production in all plants.

Phosphinothiricin Acetyltransferase (PAT) 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 plant raw agricultural commodities. \`\`Genetic

material necessary for its production\'\' means the genetic material

which comprise (1) genetic material encoding the PAT protein and (2)

its regulatory regions. \`\`Regulatory regions\'\' are the genetic
material

that control the

\[\[Page 17719\]\]

expression of the genetic material encoding the PAT protein, such as

promoters, terminators, and enhancers.

VII\. Objections and Hearing Requests

The new FFDCA section 408(g) provides essentially the same process

for persons to \`\`object\'\' to a regulation for an exemption from the

requirement of a tolerance issued by EPA under new section 408(d) as

was provided in the old section 408 and in section 409. However, the

period for filing objections is 60 days, rather than 30 days. EPA

currently has procedural regulations which governs the submission of

objections and hearing requests. These regulations will require some

modification to reflect the new law. However, until those modifications

can be made, EPA will continue to use those procedural regulations with

appropriate adjustments to reflect the new law. 0

Any person may, by June 10, 1997, file written objections to any

aspect of this 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 under the \`\`ADDRESSES\'\' section
(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, 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). Information submitted in connection with an objection or

hearing request may be claimed confidential by marking any part or all

of that information as CBI. Information so marked will not be disclosed

except in accordance with procedures set forth in 40 CFR part 2. A copy

of the information that does not contain CBI must be submitted for

inclusion in the public record. Information not marked confidential may

be disclosed publicly by EPA without prior notice.

VIII\. Public Docket

A record has been established for this rulemaking under docket

control number \[OPP-300463\]. A public version of this record, which

does not include any information claimed as CBI, is available for

inspection from 8:30 a.m. to 4 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. The

official record for this rulemaking, as well as the public version, as

described above, is kept in paper form. Accordingly, in the event there

are objections and hearing requests, 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 rulemaking record. The official rulemaking record is the paper

record maintained at the Virginia address in ADDRESSES at the beginning

of this document.

IX\. Regulatory Assessment Requirements

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 subject to

approval under 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 mandates\'\' as described in Title II of the Unfunded

Mandates Reform Act of 1995 (Pub. L. 104-4), or require prior

consultation as specified by Executive Order 12875 (58 FR 58093,

October 28, l993), or special considerations as required by Executive

Order 12898 (59 FR 7629, February 16, l994).

Because exemptions from the requirement of a tolerance established

on the basis of a petition under section 408(d) of FFDCA do not require

issuance of a proposed rule, the regulatory flexibility analysis

requirements of the Regulatory Flexibility Act (RFA), 5 U.S.C. 604(a),

do not apply. Prior to the recent amendment of the FFDCA, EPA had

treated such rulemakings as subject to the RFA; however, the amendments

to the FFDCA clarify that no proposal is required for such rulemakings

and hence that the RFA is inapplicable. Nonetheless, the Agency has

previously assessed whether establishing tolerances or exemptions from

tolerance, raising tolerance levels, or expanding exemptions adversely

impact small entities and concluded as a generic matter, that there is

no adverse impact (46 FR 24950)(May 4, 1981).

Pursuant to 5 U.S.C. 801(a)(1)(A), 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).

List of Subjects in 40 CFR Part 180

Environmental protection, Administrative practice and procedure,

Agricultural commodities, Pesticides and pests, Reporting and

recordkeeping requirements.

Dated: March 25, 1997.

Daniel M. Barolo,

Director, Office of Pesticide Programs.

Therefore, 40 CFR Chapter I 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\. Section 180.1151 is revised to read as follows:

Sec. 180.1151 Phosphinothricin Acetyltransferase (PAT) and the genetic

material necessary for its production all plants; exemption from the

requirement of a tolerance.

Phosphinothricin Acetyltransferase (PAT) 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 plant raw agricultural commodities. \`\`Genetic

material necessary for its production\'\' means the genetic material

which comprise genetic material encoding the PAT protein and its

regulatory regions. \`\`Regulatory regions\'\' are the genetic material

that control the expression of the genetic material encoding the PAT

protein, such as promoters, terminators, and enhancers.

\[\[Page 17720\]\]

Sec. 180.1175 \[Removed\]

3\. Section 180.1175 is removed.

\[FR Doc. 97-9373 Filed 4-10-97; 8:45 am\]

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