[Federal Register: July 19, 2001 (Volume 66, Number 139)]
[Rules and Regulations]
[Page 37817-37830]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr19jy01-20]

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 174

[OPP-300371B; FRL-6057-5]
RIN 2070-AC02


Exemption From the Requirement of a Tolerance Under the Federal
Food, Drug, and Cosmetic Act for Residues of Nucleic Acids that are
Part of Plant-Incorporated Protectants (Formerly Plant-Pesticides)

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: The substances plants produce for protection against pests,
and the genetic material necessary to produce these substances, are
pesticides under the Federal Insecticide, Fungicide and Rodenticide Act
(FIFRA), if humans intend to use these substances for ``preventing,
destroying, repelling or mitigating any pest.'' These substances,
produced and used in living plants, along with the genetic material
necessary to produce them, are also ``chemical pesticide residues''
under the Federal Food, Drug, and Cosmetic Act (FFDCA). EPA calls these
substances along with the genetic material necessary to produce them,
``plant-incorporated protectants.'' In this final rule, EPA exempts
from the FFDCA section 408 requirement of a tolerance, residues of
nucleic acids that are part of a plant-incorporated protectant. Nucleic
acids are ubiquitous in all forms of life, have always been present in
human and domestic animal food and are not known to cause any adverse
health effects when consumed as part of food. EPA believes there is a
reasonable certainty that no harm will result from aggregate exposure
to residues of nucleic acids that are part of a plant-incorporated
protectant.

DATES: This regulation is effective September 17, 2001. Objections and
requests for hearings must be received by EPA on or before September
17, 2001.

ADDRESSES: Written objections and hearing requests may be submitted by
regular mail, electronically, or in person. Follow the detailed
instructions for the regular mail and in person methods in Unit II. of
the SUPPLEMENTARY INFORMATION.

FOR FURTHER INFORMATION CONTACT: By mail: Philip Hutton, Biopesticides
and Pollution Prevention Division, Office of Pesticide Programs
(7511C), Environmental Protection Agency, 1921 Jefferson Davis Highway,
Arlington, VA 22202; telephone number: (703) 308-8260; e-mail address:
hutton.phil@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Document Apply to Me?

    You may be potentially affected by this action if you are a person
or company involved with agricultural biotechnology that may develop
and market plant-incorporated protectants. Potentially affected
categories and entities may include, but are not limited to:

------------------------------------------------------------------------
                                                         Examples of
           Categories                NAICS codes         potentially
                                                      affected entities
------------------------------------------------------------------------
Pesticide manufacturers          32532               Establishments
                                                      primarily engaged
                                                      in the formulation
                                                      and preparation of
                                                      agricultural and
                                                      household pest
                                                      control chemicals
------------------------------------------------------------------------
Seed companies                   111                 Establishments
                                                      primarily engaged
                                                      in growing crops,
                                                      plants, vines, or
                                                      trees and their
                                                      seeds
------------------------------------------------------------------------

[[Page 37818]]

Colleges, universities, and      611310              Establishments of
 professional schools                                 higher learning
                                                      which are engaged
                                                      in development and
                                                      marketing of plant-
                                                      incorporated
                                                      protectants
------------------------------------------------------------------------
Establishments involved in       54171               Establishments
 research and development in                          primarily engaged
 the life sciences                                    in conducting
                                                      research in the
                                                      physical,
                                                      engineering, or
                                                      life sciences,
                                                      such as
                                                      agriculture and
                                                      biotechnology
------------------------------------------------------------------------

    This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed above could also be
affected. The North American Industrial Classification System (NAIC)
codes have been provided to assist you and others in determining
whether or not this action might apply to certain entities. To
determine whether you or your business may be affected by this action,
you should carefully examine the applicable provisions of 40 CFR part
174. If you have questions regarding the applicability of this action
to a particular entity, consult the person listed under FOR FURTHER
INFORMATION CONTACT.

B. How Can I Get Additional Information, Including Copies of this
Document and Other Related Documents?

    1. Electronically.You may obtain electronic copies of this
document, and certain other related documents that might be available
electronically, from the EPA Internet Home Page at http://www.epa.gov/.
To access this document, on the Home Page select ``Laws and
Regulations,'' ``Regulations and Proposed Rules,'' and then look up the
entry for this document under the ``Federal Register--Environmental
Documents.'' You can also go directly to theFederal Register listings
at http://www.epa.gov/fedrgstr/. To access information about the EPA's
program for biopesticides go directly to the Home Page for the Office
of Pesticide Programs at http://www.epa.gov/pesticides/biopesticides.
    2. In person. The Agency has established an official record for
this action under docket control number OPP-300371B. The official
record consists of the documents specifically referenced in this
action, any public comments received during an applicable comment
period, and other information related to this action, including any
information claimed as Confidential Business Information (CBI). This
official record includes the documents that are physically located in
the docket, as well as the documents that are referenced in those
documents. The public version of the official record does not include
any information claimed as CBI. The public version of the official
record, which includes printed, paper versions of any electronic
comments submitted during an applicable comment period is available for
inspection in the Public Information and Records Integrity Branch
(PIRIB), Rm. 119, Crystal Mall #2, 1921 Jefferson Davis Hwy.,
Arlington, VA, from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The PIRIB telephone number is (703) 305-5805.

C. How Should I Handle CBI that I Want to Submit to the Agency?

    Do not submit any information electronically that you consider to
be CBI. You may claim information that you submit to EPA in response to
this document as CBI 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. In addition to one complete
version of the comment that includes any information claimed as CBI, a
copy of the comment that does not contain the information claimed as
CBI must be submitted for inclusion in the public version of the
official record. Information not marked confidential will be included
in the public version of the official record without prior notice. If
you have any questions about CBI or the procedures for claiming CBI,
please consult the person listed under FOR FURTHER INFORMATION CONTACT.

II. Objections and Hearing Requests

    Under section 408(g) of the FFDCA, as amended by the Food Quality
Protection Act (FQPA), any person may file an objection to any aspect
of this regulation and may also request a hearing on those objections.
The EPA procedural regulations which govern the submission of
objections and requests for hearings appear in 40 CFR part 178.
Although the procedures in those regulations require some modification
to reflect the amendments made to the FFDCA by the FQPA of 1996, EPA
will continue to use those procedures, with appropriate adjustments,
until the necessary modifications can be made. The new section 408(e)
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 FFDCA
sections 408 and 409. However, the period for filing objections is now
60 days, rather than 30 days.

A. What Do I Need to Do to File an Objection or Request a Hearing?

    You must file your objection or request a hearing on this
regulation in accordance with the instructions provided in this unit
and in 40 CFR part 178. To ensure proper receipt by EPA, you must
identify docket control number OPP-300371B in the subject line on the
first page of your submission. All requests must be in writing, and
must be mailed or delivered to the Hearing Clerk on or before September
17, 2001.
    1. Filing the request. Your objection must specify the specific
provisions in the regulation that you object to, and the grounds for
the objections (40 CFR 178.25). If a hearing is requested, the
objections must include a statement of the factual issues(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).
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.
    Mail your written request to: Office of the Hearing Clerk (1900),
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460. You may also deliver your request to the

[[Page 37819]]

Office of the Hearing Clerk in Rm. C400, Waterside Mall, 401 M St.,
SW., Washington, DC 20460. The Office of the Hearing Clerk is open from
8 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The
telephone number for the Office of the Hearing Clerk is (202) 260-4865.
    2. Tolerance fee payment. If you file an objection or request a
hearing, you must also pay the fee prescribed by 40 CFR 180.33(i) or
request a waiver of that fee pursuant to 40 CFR 180.33(m). You must
mail the fee to: EPA Headquarters Accounting Operations Branch, Office
of Pesticide Programs, P.O. Box 360277M, Pittsburgh, PA 15251. Please
identify the fee submission by labeling it ``Tolerance Petition Fees.''
    EPA is authorized to waive any fee requirement ``when in the
judgement of the Administrator such a waiver or refund is equitable and
not contrary to the purpose of this subsection.'' For additional
information regarding the waiver of these fees, you may contact James
Tompkins by phone at (703) 305-5697, by e-mail at tompkins.jim@epa.gov,
or by mailing a request for information to Mr. Tompkins at Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
    If you would like to request a waiver of the tolerance objection
fees, you must mail your request for such a waiver to: James Hollins,
Information Resources and Services Division (7502C), Office of
Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania
Ave., NW., Washington, DC 20460.
    3. Copies for the docket. In addition to filing an objection or
hearing request with the Hearing Clerk as described in Unit II., you
should also send a copy of your request to the PIRIB for its inclusion
in the official record that is described in Unit I.B.2. Mail your
copies, identified by docket control number OPP-300371B, to: Public
Information and Records Integrity Branch, Information Resources and
Services Division (7502C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
In person or by courier, bring a copy to the location of the PIRIB
described in Unit I.B.2. You may also send an electronic copy of your
request via e-mail to: opp-docket@epa.gov. Please use an ASCII file
format and avoid 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 6.1/8.0 file format or ASCII
file format. Do not include any CBI in your electronic copy. You may
also submit an electronic copy of your request at many Federal
Depository Libraries.

B. When Will the Agency Grant a Request for a Hearing?

    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 issues(s) in the manner sought
by the requestor would be adequate to justify the action requested (40
CFR 178.32).

III. Under What Authority is EPA Issuing this Final Rule?

    This exemption from the requirement of a tolerance is being issued
under the authority of section 408(c) of the FFDCA (21 U.S.C. 346a(c)).
Under FFDCA section 408, EPA regulates pesticide chemical residues by
establishing tolerances limiting the amounts of residues that may be
present in or on food, or by establishing exemptions from the
requirement of a tolerance for such residues. Food includes articles
used for food or drink by humans or other animals. A food containing
pesticide residues may not be moved in interstate commerce without an
appropriate tolerance or an exemption from the requirement of a
tolerance.
    Section 408 of the FFDCA applies to all ``pesticide chemical
residues'' which are defined as residues of either a ``pesticide
chemical'' or ``any other added substance that is present on or in a
commodity or food primarily as a result of the metabolism or other
degradation of a pesticide chemical'' (21 U.S.C. 321(q)(2)). The FFDCA
defines ``pesticide chemical'' as: ``any substance that is a pesticide
within the meaning of the Federal Insecticide, Fungicide, and
Rodenticide Act, including all active and inert ingredients of such
pesticide.'' (21 U.S.C. 321(q)(1)). FIFRA section 2(u) defines
``pesticide'' as: ``(1) any substance or mixture of substances intended
for preventing, destroying, repelling, or mitigating any pest, (2) any
substance or mixture of substances intended for use as a plant
regulator, defoliant, or desiccant, and (3) any nitrogen stabilizer''
(7 U.S.C. 136(u)). Under FIFRA section 2(t), the term ``pest'' includes
``(1) any insect, rodent, nematode, fungus, weed, or (2) any other form
of terrestrial or aquatic plant or animal life or virus, bacteria, or
other microorganism'' with certain exceptions (7 U.S.C. 136(t)).
    Under FFDCA section 408(c), EPA can establish an exemption from the
requirement of a tolerance for a ``pesticide chemical residue'' only if
EPA determines that granting such an exemption is ``safe'' (21 U.S.C.
346a(c)(2)(A)(i)). The FFDCA defines ``safe'' to mean that ``there is a
reasonable certainty that no harm will result from aggregate exposure
to the pesticide chemical residue, including all anticipated dietary
exposures and all other exposures for which there is reliable
information'' (21 U.S.C. 346a(c)(2)(A)(ii)). This includes exposure
through drinking water, and residential and other indoor uses, but does
not include occupational exposure. In establishing an exemption from
the requirement of a tolerance, FFDCA section 408(c) does not authorize
EPA to consider potential benefits associated with use of the pesticide
chemical in determining whether the pesticide chemical may be exempted.
    FFDCA section 408 requires EPA to give special consideration to
exposure of infants and children to the pesticide chemical residue in
establishing an exemption and to ``ensure that there is a reasonable
certainty that no harm will result to infants and children from
aggregate exposure to the pesticide chemical residue'' (21 U.S.C.
346a(b)(2)(C)(ii)(I) and (c)(2)(B)). FFDCA section 408(b)(2)(D)
specifies other general factors EPA must consider in establishing an
exemption. FFDCA section 408(c)(3) prohibits an exemption unless there
is either a practical method for detecting and measuring levels of
pesticide chemical residue in or on food or there is no need for such a
method, requiring EPA to state the reason for this determination (21
U.S.C. 346a(c)(3)).

IV. Context

A. What Role Does this Final Exemption Play in EPA's Approach toPlant-
Incorporated Protectants?

    The substances plants produce for protection against pests are
pesticides under the FIFRA definition of pesticide, if humans intend to
use these substances for ``preventing, destroying, repelling or
mitigating any pest.'' These substances, produced and used in living
plants, along with the genetic material necessary to produce them, are
designated ``plant-incorporated protectants'' by EPA.
    To understand the pivotal role this exemption plays in EPA's
approach to plant-incorporated protectants, the two following
considerations must be understood. First, the role nucleic acids

[[Page 37820]]

play in the concept of plant-incorporated protectant and how this
exemption from the FFDCA requirement of a tolerance relates to this
role. Second, how this exemption relates to the exemption from the
FFDCA requirement of a tolerance published elsewhere in a companion
document in this issue of the Federal Register for residues of the
substance portion of plant-incorporated protectants derived through
conventional breeding from sexually compatible plants.
    1. What role do nucleic acids play in the concept of plant-
incorporated protectant and how does this role relate to this
exemption? The genetic material necessary for the production of a
pesticidal substance is included in the definition of plant-
incorporated protectant because the genetic material meets, in and of
itself, the FIFRA section 2 definition of pesticide. A thorough
discussion of why the genetic material is included in the definition of
plant-incorporated protectant can be found in a companion document
published elsewhere in this issue of the Federal Register on FIFRA
regulations for plant-incorporated protectants.
    As noted in Unit III., section 408 of FFDCA applies to residues of
pesticides in or on food or feed. (Hereafter, EPA will use the term
``in food'' in the preamble to represent the concept of ``in or on food
or feed.'') Under section 408 of the FFDCA, the term residue is applied
broadly to include residues of the pesticide itself and residues that
are present in the food as a result of the metabolism or other
degradation of the pesticide. EPA anticipates that for plant-
incorporated protectants, the residues will consist of the pesticidal
substance and any inert ingredient as defined for plant-incorporated
protectants (e.g., any selectable marker), and the genetic material
necessary for production of the pesticidal substance and any inert
ingredient. In instances where the pesticidal substance is a nucleic
acid (e.g., satellite RNA from plant viruses), EPA anticipates these
residues will be the nucleic acid functioning as the pesticidal
substance and the nucleic acid comprising the genetic material
necessary for the production of the pesticidal substance (as well as
any inert ingredient and the genetic material necessary to produce the
inert ingredient). For anti-sense technology, EPA anticipates that
these residues will consist of the the anti-sense RNA, and the DNA
encoding the anti-sense RNA (as well as any inert ingredient and the
genetic material necessary to produce the inert ingredient).
    In developing its approach to plant-incorporated protectants, EPA
recognized that nucleic acids are ubiquitous in all forms of life,
including food plants. There is a long history of consumption by humans
of nucleic acids in food and the Agency knows of no instance where
nucleic acids have been associated with any toxic effects related to
the consumption of food. It is therefore appropriate to exempt residues
of nucleic acids that are part of a plant-incorporated protectant from
the FFDCA section 408 requirement of a tolerance.
    For EPA to exempt any residue of a pesticide, including any residue
of a plant-incorporated protectant, from regulation under FFDCA section
408(e), EPA must find that there is a reasonable certainty that no harm
will result from aggregate exposure to the residues, including all
anticipated dietary exposures and all other exposures, for which there
is realiable information. EPA is exempting in this action residues of
nucleic acids that are part of plant-incorporated protectant active and
inert ingredients, because it has determined that there is a reasonable
certainty that no harm will result from aggregate exposure to the
residues, including all anticipated dietary exposures and all other
exposures for which there is reliable information. This exemption from
the requirement of a tolerance applies to the nucleic acid portion of
all plant-incorporated protectants.
    2. How does this exemption relate to the exemption from the FFDCA
requirement of a tolerance for the substance portion of plant-
incorporated protectants derived through conventional breeding from
sexually compatible plants? This exemption can be paired with EPA's
decision, published elsewhere in a companion document in this issue of
the Federal Register, to exempt residues of pesticide chemical residues
derived through conventional breeding from sexually compatible plants.
    Because of these actions, all residues of plant-incorporated
protectants derived through conventional breeding from sexually
compatible plants are exempt from FFDCA section 408 requirements.

B. Does this Final Rule Have Any Relevance to Other Types of
Pesticides?

    Nonviable plant tissues, organs or parts that are used as
pesticides, will not be covered by this exemption. Residues of such
pesticides are subject to the regulations found in 40 CFR parts 177
through 180 rather than 40 CFR part 174. An example of this type of
pesticide would be the powder, produced by drying and grinding cayenne
pepper, dusted on plants to protect them from pests.
    Residues of substances that are isolated from a plant's tissues and
then applied to plants and/or to food for pest control will not be
covered by this exemption. Residues of these types of pesticides in
formulations such as those for foliar application are subject to
regulations found in 40 CFR parts 177 through 180 rather than 40 CFR
part 174. An example of this type of pesticide would be pyrethrum
isolated from chrysanthemum plants, formulated with other ingredients
for foliar application, and sprayed onto other plants for pest control.
    Residues of substances that are synthesized will not be covered by
this exemption. Residues of such pesticides are subject to regulations
found in 40 CFR parts 177 through 180 rather than 40 CFR part 174. An
example of this type of pesticide is the herbicide atrazine.

C. What is the History of this Final Rule?

    This final rule is an additional step in fully implementing the
``Coordinated Framework for Regulation of Biotechnology'' of the United
States of America which was published in the Federal Register by the
Office of Science and Technology Policy (OSTP) on June 26, 1986 (51 FR
23302).
    EPA sponsored, or cosponsored with other Federal agencies, three
conferences dealing with plant related issues: On October 19-21, 1987,
a meeting on ``Genetically Engineered Plants: Regulatory
Considerations'' at Cornell University, Ithaca, New York; on September
8-9, 1988, a ``Transgenic Plant Conference'' in Annapolis, Maryland; on
November 6-7, 1990, a conference on ``Pesticidal Transgenic Plants:
Product Development, Risk Assessment, and Data Needs'' in Annapolis,
Maryland. Information from these conferences has been incorporated as
appropriate in development of this final rule.
    In developing its approach to plant-incorporated protectants, EPA
requested the advice of two scientific advisory groups in three
meetings. On December 18, 1992, pursuant to section 25 of FIFRA, a
subpanel of the FIFRA Scientific Advisory Panel (SAP) was convened to
review a draft policy on plant-pesticides (now called plant-
incorporated protectants) and to respond to a series of questions posed
by the Agency primarily on EPA's approach under FIFRA. On July 13,
1993, EPA requested the advice of a subcommittee of the EPA
Biotechnology Science Advisory Committee (BSAC) on a series of
scientific questions dealing with approaches to plant-pesticides under
FFDCA. On January 21, 1994, a

[[Page 37821]]

joint meeting of the subpanel of the SAP and the BSAC Subcommittee was
held and EPA asked advice on EPA's approach to plant-pesticides under
both statutes. Advice from these scientific advisory groups was
considered in finalizing this final rule.
    EPA published in the November 23, 1994 Federal Register, a package
of five separate documents (59 FR 60496, 60519, 60535, 60542 and 60545)
(FRL-4755-2, FRL-4755-3, FRL-4755-4, FRL-4755-5, FRL-4755-8) which
described EPA's policy and proposals for plant-pesticides under FIFRA
and FFDCA.
    On July 22, 1996, EPA published a supplemental document in the
Federal Register (61 FR 37891) (FRL-5387-4) on one aspect of its
November 23, 1994, Federal Register document, i.e., how the concept of
inert ingredient related to plant-pesticides.
    In August of 1996, Congress enacted the FQPA which amended FFDCA
and FIFRA. On May 16, 1997, EPA published in the Federal Register a
supplemental document (62 FR 27132) (FRL-5717-2) to provide the public
with an opportunity to comment on EPA's analysis of how certain FQPA
amendments to FFDCA and FIFRA apply to the proposed exemption from the
requirement of a tolerance for residues of nucleic acids that are part
of a plant-pesticide.
    On April 23, 1999, EPA published a supplemental document (64 FR
19958) (FRL-6077-6) in the Federal Register soliciting comment on
whether to change the name of this type of pesticide.
    The documents and the reports of the meetings described above are
available in the official record for the rulemaking as described in
Unit X.

V. What are the Key Features of the Proposed Exemption?

    The development of this exemption consists of a proposed rule that
appeared in the November 23, 1994, Federal Register (59 FR 60542) and
two supplemental documents; one document that appeared in the July 22,
1996, Federal Register (61 FR 37891) and a second document that
appeared in the May 16, 1997, Federal Register (62 FR 27142).

A. November 23, 1994, Federal Register Proposed Rule

    In the November 23, 1994, Federal Register document, EPA proposed
at 40 CFR 180.1138 to exempt residues of nucleic acids that are part of
a plant-pesticide (now called a plant-incorporated protectant) from the
requirement of a tolerance (59 FR 60542). Specifically, EPA proposed
that ``residues of nucleic acids produced in living plants as part of a
plant-pesticide active or inert ingredient, including both
deoxyribonucleic and ribonucleic acids,'' would be exempt from the
requirement of a tolerance. ``Nucleic acids'' were described as
``ribosides or deoxyribosides of adenine, thymine, guanine, cytosine,
and uracil and the polymers of these ribosides and deoxyribosides and
does not apply to nucleic acid analogues.''
    ``Active ingredient,'' when referring to plant-incorporated
protectants only, was described as ``a pesticidal substance that is
produced in a living plant and the genetic material necessary for the
production of the substance, where the substance is intended for use in
the living plant.''
    ``Inert ingredient,'' when referring to plant-incorporated
protectants only, was described as ``any substance, such as a
selectable marker, other than the active ingredient, and the genetic
material necessary for the production of the substance, that is
intentionally introduced into a living plant along with the active
ingredient, where the substance is used to confirm or ensure the
presence of the active ingredient.''
    The proposal to exempt nucleic acids that are part of a plant-
incorporated protectant from the requirement of a tolerance was based
on the ubiquity of nucleic acids in human and domestic animal food and
the consumption of food containing nucleic acids without observed
adverse health effects. Nucleic acids are widespread in foods and as
part of a balanced diet, do not have toxic or pathogenic effects on
animals or humans.
    EPA also addressed in the proposal the status of nucleic acids used
in anti-sense technology. In the proposal, EPA stated its belief that
nucleic acids involved in this technology would qualify for the
proposed exemption. The rationale used in the proposal to support
exemption of naturally-occurring nucleic acids applies to nucleic acids
used in anti-sense technology, as the anti-sense RNA and DNA are
composed of the same naturally-occurring nucleic acids commonly found
in living cells (ribosides or deoxyribosides of cytosine, guanine,
adenine, thymine, and uracil).
    In 1994, the Agency clearly stated that it was not proposing to
exempt nucleic acid analogues from the requirement of a food tolerance.
Certain nucleic acid analogues are being developed as therapeutic
agents for human diseases (e.g., dideoxycytidine) and nucleic acid
analogues could conceivably be developed and used as pesticides. These
analogues are not naturally-occurring and those used as therapeutic
agents frequently have significant toxicity associated with their use.
The intent of EPA's 1994 proposal was to exempt only the naturally-
occurring nucleic acids (ribosides or deoxyribosides of cytosine,
guanine, adenine, uracil, and thymine) and polymers of such substances
commonly found in living cells that serve as the mechanism of encoding
traits associated with pesticidal substances produced by plants. The
risk assessment supporting exemption for naturally-occurring nucleic
acids does not support exemption of nucleic acid analogues (e.g.,
dideoxycytidine), or polymers containing such analogues.

B. What Issues Were Discussed in the Supplemental Documents?

    1. July 22, 1996. On July 22, 1996, EPA published a supplemental
document in the Federal Register (61 FR 37891) on one aspect of its
November 23, 1994, Federal Register document, i.e., how the concept of
inert ingredient related to plant-incorporated protectants.
    2. May 16, 1997. In August of 1996, FFDCA and FIFRA were amended by
the FQPA. On May 16, 1997, EPA published in the Federal Register, a
supplemental document (62 FR 27142) to provide the public with an
opportunity to comment on EPA's analysis of how certain FQPA amendments
to FFDCA and FIFRA affect the proposed exemption from the requirement
of a tolerance for residues of nucleic acids that are part of a plant-
incorporated protectant.
    EPA stated in the May 16 document its belief that most of the
substantive factors that the FFDCA now requires EPA to consider in
evaluating pesticides were considered when it proposed the exemption
(59 FR 60542, November 23, 1994). EPA, thus, in the supplemental
document, specifically sought comment only on its evaluation of the
requirements imposed by FQPA that the Agency had not addressed in the
proposal. EPA sought comment on the following five considerations.
First, EPA's conclusion that there are no substances outside of the
food supply that may have a cumulative toxic effect with residues of
nucleic acids produced in plants as part of a plant-incorporated
protectant. Second, EPA's conclusion that there are no additional
substances outside the food supply that are related, via a common
mechanism of toxicity, to residues of nucleic acids produced in plants
as part of a plant-incorporated protectant, for which EPA must consider
exposure in aggregate with

[[Page 37822]]

nucleic acids. Third, commenters who possess information on nucleic
acids causing estrogenic effects were requested to send such
information to EPA. Fourth, EPA described in greater detail the
rationale supporting the statement made in the 1994 Federal Register
document (59 FR at 60513) that ``plant-pesticides are likely to present
a limited exposure of pesticidal substances to humans. In most cases,
the predominant, if not the only route of exposure will be dietary.
Significant respiratory and dermal exposures will be unlikely.'' No
comments were received on this statement during the first comment
period for the proposal. The public was given the opportunity to
comment on EPA's more detailed rationale supporting the statement.
Fifth, EPA also described in greater detail how the rationale presented
in the 1994 Federal Register document (59 FR at 60538, November 23,
1994) concerning the safety for human consumption of food containing
residues of nucleic acids produced in plants as part of a plant-
incorporated protectant applies to infants and children. The public was
given the opportunity to comment on EPA's more detailed rationale
addressing infants and children as part of the larger human population.

VI. What are the Key Features of the Final Rule?

    In this final rule, EPA exempts residues of nucleic acids that are
part of a plant-incorporated protectant. The following language is
added to 40 CFR 174.475:
    Residues of nucleic acids that are part of a plant-incorporated
protectant are exempt from the requirement of a tolerance.
    Definitions at 40 CFR 174.3 relevant to the language at 40 CFR
174.475 include:
    ``Nucleic acids'' means ribosides or deoxyribosides of adenine,
thymine, guanine, cytosine and uracil; polymers of the deoxyribose-5'-
monophosphates of thymine, cytosine, guanine, and adenine linked by
successive 3'-5'-phosphodiester bonds (also known as deoxyribonucleic
acid); and polymers of the ribose-5'-monophosphates of uracil,
cytosine, guanine and adenine linked by successive 3'-5'-phosphodiester
bonds (also known as ribonucleic acid). The term does not apply to
nucleic acid analogues (e.g., dideoxycytidine), or polymers containing
nucleic acid analogues.
    Other definitions, relevant for plant-incorporated protectants
only, can be found at 40 CFR 174.3 and are discussed in a companion
document on FIFRA regulations published elsewhere in this issue of the
Federal Register.
    In this final rule, ``plant'' means an organism classified using
the 5-kingdom classification system of Whittaker (Ref. 1) in the
kingdom, Plantae. Therefore, the term ``plant'' includes, but is not
limited to, bryophytes such as mosses, pteridophytes such as ferns,
gymnosperms such as conifers, and angiosperms such as most major crop
plants.
    This exemption applies to the residues of genetic material
necessary for the production of pesticidal substances in living plants,
to residues of the genetic material necessary to produce any inert
ingredient, to residues of nucleic acids used as the pesticidal
substance (e.g., satellite RNA from plant viruses), and to residues of
nucleic acids used in anti-sense technology. This exemption applies to
naturally-occurring nucleic acids regardless of the sequence of the
nucleic acid, the source of the sequence, or the function (e.g.,
template for a protein, or a regulatory element such as a promotor) the
sequence encodes.
    This final rule exempts only naturally-occurring nucleic acids,
i.e., ribosides or deoxyribosides of adenine, guanine, cytosine,
thymine, and uracil; polymers of the deoxyribose-5'-monophosphates of
thymine, cytosine, guanine, and adenine linked by successive 3'-5'-
phosphodiester bonds (also known as deoxyribonucleic acid); and
polymers of the ribose-5'-monophosphates of uracil, cytosine, guanine
and adenine linked by successive 3'-5'-phosphodiester bonds (also known
as ribonucleic acid). It does not apply to nucleic acid analogues
(e.g., didioxycytidine) or polymers containing nucleic acid analogues.

VII. How Do the Proposed Rule and Final Rule Differ?

    This exemption from the requirement of a tolerance is adopted with
a few changes from the proposed rule published in 1994 (59 FR 60545).
EPA has changed the name of this type of pesticide from ``plant-
pesticide'' to ``plant-incorporated protectant,'' as described in the
companion document on FIFRA regulations for plant-incorporated
protectants published elsewhere in this issue of the Federal Register.
    Some modifications have been made to the text of the exemption and
to associated definitions, for purposes of clarification. The
definition of the term ``nucleic acids'' was modified to provide
greater technical clarity; this modification does not change the scope
of the exemption. These modifications are discussed in this document. A
discussion of modifications to other relevant definitions, including an
analysis of comments on those definitions, can be found in a companion
document published elsewhere in this issue of the Federal Register on
FIFRA regulations for plant-incorporated protectants.
    When EPA proposed this exemption at 40 CFR 180.1138 from the
requirement of a tolerance in 1994, it also stated its intention (59 FR
at 60520) to establish a new 40 CFR part 174 specifically for plant-
incorporated protectants. This new 40 CFR part 174 is being established
in a companion document published elsewhere in this issue of the
Federal Register. EPA adds this exemption from the requirement of a
tolerance in Sec. 174.475, subpart W, rather than adding it to 40 CFR
part 180 as proposed.

VIII. Discussion of Final Rule and Public Comments

    In this unit, EPA discusses the final rule and summarizes the
comments it received on the November 23, 1994, proposed rule and
subsequent supplemental documents. EPA reviewed and considered all
comments received on the proposed rule and the supplemental documents
and prepared detailed responses to these comments, which can be found
at appropriate points in this preamble in its discussion of the final
rule and the statutory finding.
    In addition to being addressed in this preamble, comments are also
addressed in the Agency's summary of public comments and EPA's response
on issues associated with plant-incorporated protectants (Ref. 2).

A. From Whom Did EPA Receive Comment?

    In response to the package of documents published in the Federal
Register in 1994, EPA received letters from industry, academia,
professional and trade associations, government agencies, state
regulatory authorities, public interest groups and private citizens.
Some of the commenters sent separate letters for each of the five
dockets associated with the 1994 Federal Register documents. Other
commenters sent a single letter addressing all five dockets. On July
22, 1996, EPA published a supplemental document seeking comment on the
concept of inert ingredient with regard to plant-incorporated
protectants. EPA received comments on this supplemental document. On
May 16, 1997, EPA published a supplemental document to provide the
public an

[[Page 37823]]

opportunity to comment on EPA's analysis of how certain amendments to
FFDCA and FIFRA by the FQPA affected this proposed exemption. EPA
received comments on the supplemental document. Copies of all comments
received are available in the official record for this final rule as
described in Unit X.

B. Exemption of Residues of Nucleic Acids that are Part of a Plant-
Incorporated Protectant

    On November 23, 1994 (59 FR 60542), EPA proposed to exempt from the
FFDCA requirement of a tolerance, residues of nucleic acids (i.e.,
deoxyribonucleic acid and ribonucleic acid) produced in plants as part
of a plant-incorporated protectant active or inert ingredient.
    During the comment period for the 1994 proposal, EPA received 17
comments. Almost all of these comments supported the proposed
exemption. Commenters agreed that nucleic acids are abundant in all
plants and that humans have been and are routinely exposed to large
amounts of nucleic acids as a normal part of their diet. One commenter
stated that EPA's proposed exemption from the requirement of a
tolerance for nucleic acids is consistent with the position of the Food
and Drug Administration (FDA) with regard to nucleic acids.
    In response to the July 22, 1996, supplemental document, EPA
received 14 comments on the concept of inert ingredient with regard to
plant-incorporated protectants. None of these comments addressed the
issue of inert ingredient with regard to this exemption. (Comments on
other aspects of the concept of inert ingredient are discussed in a
companion document published elsewhere in this issue of the Federal
Register on FIFRA regulations for plant-incorporated protectants).
    In response to the May 16, 1997, supplemental document, EPA
received four comments. All four comments supported the exemption. One
of the four commenters indicated they knew of no information on
substances, having cumulative effects or common mechanisms of toxicity
with residues of nucleic acids, that would have a bearing on this
exemption from the requirement of a tolerance. No comments were
received on the other considerations raised by EPA in the supplemental
document.

C. What is the Language of the Exemption?

    No comments on the language of the proposed exemption were
received. EPA modified the language of the proposed exemption and the
proposed definition of nucleic acids, however, for greater clarity. In
this unit, EPA discusses those changes. EPA also discusses what
``nucleic acids'' means in the context of this exemption, and how EPA's
decision on inert ingredients for plant-incorporated protectants
affects this exemption.
    1. What does the term ``nucleic acid'' mean? Genetic material,
including genetic material necessary for the production of the
pesticidal substance, is composed of nucleic acids. Chemically, there
are two types of nucleic acids: Deoxyribonucleic acid (DNA) and
ribonucleic acid (RNA) (Ref. 3). DNA is a polymer of purine and
pyrimidine base deoxyribonucleoside monophosphates (also called
deoxynucleotides) that are commonly referred to by the names of purine
and pyrimidine bases: Adenine (A), cytosine (C), guanine (G), and
thymine (T). A deoxynucleotide is made up of a sugar, a phosphate, and
one of the four bases. In the DNA polymer, the sugars and phosphates of
the deoxynucleotides are hooked together to form the ``backbone.'' One
base is attached to each sugar in the sugar-phosphate backbone. RNA
polymers are formed of similar linkages. RNA is a polymer of purine and
pyrimidine base riboside monophosphates (also called nucleotides). The
RNA nucleotides are also referred to by their base names: Adenine (A),
cytosine (C), guanine (G), and uracil (U). In the RNA polymer, the
sugar and phosphate moieties are also hooked together to form a
backbone, with one base attached to each sugar moiety in the backbone.
The information encoded in nucleic acids (either DNA or RNA) is
determined by the sequence in which the bases are attached to the
sugar-phosphate backbone (Ref. 3, 4). Nucleic acids encode all of the
information necessary for the functioning of an organism. When a
nucleic acid encoding a pesticidal substance is stably integrated into
a plant, that plant and its progeny will, in most cases, have the
potential to produce the pesticidal substance.
    The ``nucleic acids'' of this exemption refer to the nucleic acids
encoding the information for making polypeptides (proteins) which are
the pesticidal substances or inert ingredients (e.g., selectable
markers), or alternatively, encoding for proteins necessary for making
(anabolizing) these substances. There may also be instances wherein
nucleic acids may serve as the pesticidal substance. For example,
satellite RNA of plant viruses may be used in strategies to control
viral diseases in plants. In this situation, the RNA may be the
pesticidal substance intended to control the pest. This exemption also
applies to such RNA. This exemption for nucleic acids also applies to
the DNA and RNA used in ``anti-sense'' technology, when this technology
is used for pest resistance in plants. ``Anti-sense'' technology is
used to block the production of a targeted enzyme or cellular
component. In this technology, a segment of DNA encoding an RNA
complementary (anti-sense) to the RNA necessary to produce the targeted
enzyme or cellular component is introduced into the plant. For example,
a company might wish to shut down an enzyme essential for pathogenesis
by an agent that can cause disease in plants. To do so, the company
would introduce into the genetic material of the plant, DNA encoding
the anti-sense version of the RNA necessary to produce the targeted
enzyme. The anti-sense version would bind to the normal version of the
RNA necessary to produce the targeted enzyme. The normal (``sense'')
version of the RNA would then no longer be available for processing in
the cell, and, thus, the enzyme necessary for pathogenesis would not be
produced. Because the essential enzyme cannot be produced, the disease-
causing agent is not able to carry out one of the functions necessary
for pathogenesis.
    2. What modifications were made to the language of the exemption?
In 1994, EPA proposed that residues of ``nucleic acids produced in
living plants as part of a plant-pesticide active or inert ingredient,
including both deoxyribonucleic and ribonucleic acids, are exempt from
the requirement of a tolerance.'' In this final rule, EPA removes from
the language of the exemption the phrase ``produced in living plants''
as this concept is part of the definition of plant-incorporated
protectant. EPA was concerned that use of the phrase in the language of
the exemption might cause some confusion because of this redundancy of
concept. EPA also removed from the language of the proposed exemption,
the phrase ``including both deoxyribonucleic and ribonucleic acids,''
also because of redundacy as the phrase appears in the definition of
nucleic acids. Finally, EPA spelled out for greater technical clarity
in the definition at 40 CFR 174.3 what substances are included in the
concept of ``nucleic acids'' for plant-incorporated protectants, and
what substances are excluded from the concept.
    3. How does the concept of inert ingredient relate to this
exemption? In the November 23, 1994, Federal Register document, EPA
stated that an inert ingredient for plant-incorporated

[[Page 37824]]

protectants would be ``any substance, such as a selectable marker,
other than the active ingredient, and the genetic material necessary
for the production of the substance, that is intentionally introduced
into a living plant along with the active ingredient, where the
substance is used to confirm or ensure the presence of the active
ingredient'' (59 FR 60521). In a companion document published elsewhere
in this issue of the Federal Register, EPA describes its consideration
of inert ingredients in light of existing regulations and comments
received in response to both the November 23, 1994, Federal Register
document (59 FR 60534) and the 1996 supplemental document (61 FR 37891,
July 22, 1996) discussing the Agency's treatment of selectable markers
as inert ingredients for plant-incorporated protectants. In the
companion document published elsewhere in this Federal Register, EPA
describes its determination that it will apply the concept of inert
ingredients to plant-incorporated protectants consistent with the 1994
proposal.
    The preamble discussion in the 1994 Federal Register document (59
FR at 60544) of the rationale supporting the proposed rule to exempt
residues of nucleic acids from the requirement of a tolerance addressed
the nucleic acids necessary to produce any substance, such as a
selectable marker, used to confirm or ensure the presence of the active
ingredient. The exemption at 40 CFR 174.475 contains language
indicating the exempt status of residues of the genetic material
necessary for the production such substances.

IX. Statutory Finding

A. What Methodology Did EPA Use to Assess these Residues?

    For most pesticides (e.g., chemical pesticides), EPA's dietary risk
evaluation relies on data generated by testing in laboratories using
representative animal models to estimate acute, subchronic, or chronic
hazard end-points (e.g., acute toxicity, carcinogenicity, developmental
toxicity). Conclusions from animal models are used to assess dose-
response and describe such endpoints for potential human hazard. Other
information, including residue data and information generated by use of
mathematical models, are used to develop human exposure estimates.
These exposure and hazard components are combined to quantify the
potential risk associated with the pesticide's use. Uncertainty factors
are often used in the risk assessment to account for extrapolation from
animal models to human toxicity and from limited studies using humans
to the larger population. The data requirements describing the types of
information to be generated and other guidance for assessing dietary
risk are detailed in 40 CFR part 158.
    The questions posed as part of the risk assessment in evaluating
residues of most pesticides (e.g., chemical pesticides) can also be
posed for pesticide chemical residues that are the subject of this
exemption, and 40 CFR part 158 can be used as guidance in evaluating
these substances for hazard end-points (including, for example, acute
toxicity, carcinogenicity, and developmental toxicity). To address the
hazard endpoints described in 40 CFR part 158 for residues of nucleic
acids that are part of a plant-incorporated protectant, EPA relied on a
very large body of information found for the most part in the public
scientific literature. A very large body of experience with actual
human dietary consumption, over hundreds if not thousands of years,
exists for the substances that are the subject of this exemption. And
thus, a large and varied amount of information developed through
systematic scientific study exists in the literature that can be used
for assessing the risk of exempting nucleic acids. For example, there
are numerous epidemiological studies on humans on foods containing
nucleic acids (Refs. 5, 6, 7, 8, 9, 10, 11, 12, and 13), as well as a
large literature on constituents of food from plants accumulated by a
century of systematic study (Ref. 4).
    EPA also considered other information in the literature in
evaluating the potential for exposure to residues of nucleic acids that
are part of a plant-incorporated protectant. Plant-incorporated
protectants are produced within the living plant itself and the
pesticidal substance is used in situ in a living plant to protect
against pests, in contrast to most other pesticides which must be
applied to the plant or the area around the plant (Ref. 14). Because a
plant-incorporated protectant is produced and used within the plant,
physiological constraints limit the amount of residue produced by the
plant (Ref. 14). Because a plant-incorporated protectant is within the
plant, routes by which other organisms may be exposed to the plant-
incorporated protectant may be more limited; e.g., dietary exposure is
likely to be the predominant route of exposure.
    EPA relied on data in the area of plant genetics to provide
information and knowledge on the genetic material that is necessary for
the production of the pesticidal substances (Ref. 3). The Agency used
experimental data derived from the science of phytopathology to
characterize the disease and pest resistance mechanisms known to occur
in plants (Ref. 15). EPA also considered information from the field of
plant physiology regarding plant metabolism, particularly the
metabolism of nucleic acids in plants (Refs. 3 and 17). EPA also used
information from the fields of biochemistry, microbial ecology and
ecology (Refs. 3, 15, 17, and 21).
    For this exemption, EPA's risk assessment was based primarily on
information in the publically available scientific literature as well
as through experience with breeding and growing agricultural plants,
and preparing and consuming food from such plants. Such food contains
nucleic acids, as nucleic acids are ubiquitous in nature and in the
food supply (Ref. 4). In exempting residues in food of nucleic acids
that are part of a plant-incorporated protectant from the requirement
of a tolerance, EPA considered health risks to the general population,
including infants and children. Infants and children have always and
currently consume food containing nucleic acids. There is no evidence
that nucleic acids, as components of food, present a different level of
dietary risk for infants and children than they would for the adult
population. EPA's risk assessment also included subgroups as part of
the general population, (i.e., differences in diet due to the influence
of culture), and allowed for consumption pattern differences of such
subgroups.
    EPA believes human experience in consuming food containing nucleic
acids combined with the numerous epidemiological and other studies and
the knowledge of plant genetics, plant physiology, phytopathology,
microbial ecology, ecology, biochemistry and plant breeding are the
appropriate considerations in evaluating the potential risks of
residues of nucleic acids that are part of a plant-incorporated
protectant. All of these bases of knowledge and experience were
integral to EPA's assessment of exposures and hazards associated with
residues of nucleic acids that are part of a plant-incorporated
protectant.

B. What Factors Has EPA Considered in Making the Findings Required by
408(c) of the FFDCA?

    FFDCA section 408(c)(2)(B) requires EPA to consider several factors
in determining whether to exempt a pesticide from the requirement of a
tolerance. Information relevant to EPA's consideration of these factors
with regard to this exemption is contained in this document, as well as
in other

[[Page 37825]]

documents in the record for this final rule as described in Unit X.
    1. Validity, completeness and reliability of available data. As
noted in Unit IX.A., EPA's risk assessment was based primarily on an
analysis of human experience with breeding and growing agricultural
plants, and preparing and consuming food from such plants, and
associated epidemiological studies, nutritional assessments with human
volunteers and animal model testing (Refs. 5, 6, 7, 8, 9, 10, 11, 12,
13). EPA combined this information with knowledge from the disciplines
of plant genetics, plant physiology, phytopathology, microbial ecology,
ecology, biochemistry and plant breeding (Refs. 3, 15, 17, and 21, for
example) to evaluate the potential risks of residues of nucleic acids
that are part of a plant-incorporated protectant. EPA considered the
validity, completeness and reliability of all available information.
EPA concluded that this information was valid, complete and reliable,
and adequately addressed the issues of hazard and exposure with regard
to residues of nucleic acids in food.
    2. Nature of toxic effect. EPA considered the nature of any toxic
effects shown by this information to be caused by residues of nucleic
acids that are part of a plant-incorporated protectant active or inert
ingredient. Nucleic acids are widespread in foods (Ref. 4) and are not
associated with toxic effects on animals or humans (Ref. 4, 18).
Neither nucleic acids nor the substances of which nucleic acids are
composed are known to be acute toxicants, but like proteins and other
normal constituents of food, may cause indirect, adverse metabolic
effects if consumed exclusively at high doses over a long period of
time in the absence of a balanced diet. A person consuming food from
plants containing residues of nucleic acids would not be consuming
nucleic acids exclusively, and nucleic acids do not occur at these high
doses in food plants. Consumption of nucleic acids in food has not been
associated with any toxic effects (Ref. 18). Thus, because the residues
of nucleic acids that are part of a plant-incorporated protectant are
no different than other nucleic acids, including those that have been
safely consumed, consumption of food containing residues of nucleic
acids that are part of a plant-incorporated protectant are not expected
to present a toxic effect. Simiarly, the nucleic acids in food from
plants have not been associated with pathogenic effects on humans or
other animals (Ref. 16), and residues in food of nucleic acids that are
part of a plant-incorporated protectant are not expected to have
pathogenic effects on humans or other animals.
    3. Relationship of studies to humans. EPA considered the available
information concerning the relationship of this information on nucleic
acids in foods to human risk. The effect of nucleic acids on humans was
assessed in light of the known presence of nucleic acids in all foods
(Refs. 3 and 4) and the long history of human consumption of plant food
containing nucleic acids, i.e., food derived from crop plants and from
animals that consume forage and other crops containing nucleic acids.
The epidemiological studies supply data generated on humans and thus
are directly applicable to humans. Information from the disciplines of
plant genetics, plant physiology, phytopathology, microbial ecology,
ecology, biochemistry (including studies on the constituents of food)
and plant breeding can be used to predict effects on humans. Nucleic
acids in foods do not have a toxic effect and cause no adverse effects
to humans. Because information on human consumption of food containing
nucleic acids was available and adequately addressed the issues of
hazard and exposure, EPA relied primarily on the epidemiological and
other information generated directly from humans rather than relying on
data generated in the laboratory through animal testing.
    4. Dietary consumption patterns. EPA considered the available
information on the varying dietary consumption patterns of consumers
and major identifiable consumer subgroups as it pertains to residues of
nucleic acids that are part of a plant-incorporated protectant in food.
Issuance of this exemption from the requirement of a tolerance is not
expected to alter the current consumption pattern of nucleic acids by
consumers or major identifiable consumer subgroups. Nucleic acids are
ubiquitous in all living organisms and in the food supply; thus, no
subgroup is likely to receive a greater exposure nor a different
exposure than any other subgroup.
    5. Available information concerning cumulative effects of the
pesticide chemical residue and other substances that have a common
mechanism of toxicity. EPA has examined the available information as
described in Unit IX.A. and Unit IX.B.1., on the cumulative effect of
residues in food of nucleic acids that are part of a plant-incorporated
protectant, and other substances that may have a common mechanism of
toxicity. Nucleic acids are widespread in food (Ref. 4) and have not
been associated with direct toxic effects to animals or humans (Ref.
18). Because nucleic acids in foods have no human toxicity, no
cumulative effects can be identified for residues of nucleic acids that
are part of a plant-incorporated protectant. The FQPA also directs the
Agency to examine whether there are other substances that have a common
mechanism of toxicity with nucleic acids that are part of a plant-
incorporated protectant. Based on available information which indicates
that nucleic acids in food have no human toxicity, EPA is not aware of
any other substances that might have a common mechanism of human
toxicity with residues of nucleic acids that are part of a plant-
incorporated protectant.
    The four comments EPA received on the May 16, 1997, supplemental
document all supported the exemption. One of the four commenters
indicated they knew of no information on substances, having cumulative
effects or common mechanisms of toxicity with residues of nucleic
acids, that would have a bearing on the exemption from the requirement
of a tolerance.
    EPA is not aware of any substances outside of the food supply that
may have a common mechanism of toxicity with nucleic acids that are
part of a plant-incorporated protectant since nucleic acids in food are
not toxic. EPA has identified nucleic acid analogues (e.g.,
dideoxycytidine, zidovudine, dideoxyinosine) as substances having some
level of toxicity (Ref. 19, 20). However, the mechanisms of toxicity of
such analogues are not cumulative with that of residues of naturally-
occurring nucleic acids.
    6. Aggregate exposure of consumers including non-occupational
exposures. EPA considered the available information on the aggregate
exposure level of consumers to residues of nucleic acids that are part
of a plant-incorporated protectant and to other related substances
including nucleic acids that are not part of a plant-incorporated
protectant. This included a consideration of exposures from dietary
sources as well as from other non-occupational sources. Plant-
incorporated protectants and their residues are likely to present a
limited exposure to humans.
    Nucleic acids produced in living plants are part of the metabolic
cycles of plants. They are biotic and thus subject to the processes of
biodegradation and decay that all biotic materials undergo (Ref. 21).
Biotic materials are broken down to constituent parts through the
enzymatic processes of living organisms, and these constituent parts
used as the building

[[Page 37826]]

blocks to make other biotic substances. Because of these
characteristics, the potential for exposures to the residues to occur,
beyond direct physical exposure to the plant, is limited.
    The residues that are the subject of this exemption are
biodegradable to their constituent elements through catabolism by
living organisms (Ref. 21). Because of their biodegradable nature,
residues of nucleic acids do not bioaccumulate (bioaccumulation occurs
when a substance is taken into the body through processes such as
eating, and as the body is unable to either break the substance down or
eliminate it, the substance accumulates in the tissues) or biomagnify
in the tissues of living organisms (biomagnification occurs when a
substance bioaccumulates in the bodies of organisms lower in the food
chain, and as predators higher in the food chain consume organisms
lower in the food chain, more and more of the substance accumulates in
the bodies of organisms higher in the food chain). Humans ingesting the
nucleic acids in food are likely to quickly degrade them and use their
constituent elements as nutrients.
    In most cases, the predominant exposure route will be dietary.
Exposure through other routes is unlikely because the substances are in
the plant tissue and thus are found either within the plant or in close
proximity to the plant. This is particularly true for residues of
nucleic acids that are part of a plant-incorporated protectant, because
large polymers are susceptible to rapid degradation. EPA expects non-
dietary exposure (i.e., non-food oral, dermal and inhalation) in non-
occupational settings to be negligible.
    i. Dietary exposure. EPA considered dietary exposure to nucleic
acids that are part of a plant-incorporated protectant. Nucleic acids
are widespread in foods (Ref. 4), and all foods consumed by humans
contain nucleic acids. As nucleic acids are ubiquitous in food, EPA
concluded that all humans are exposed to nucleic acids throughout their
lives as part of their diet. As described in Unit IX.A. and Unit
IX.B.1., a large base of experience exists, including information on
human dietary exposure, for foods that undoubtedly contain nucleic
acids. Nucleic acids in food are not toxic and there is no evidence
that consumption of nucleic acids in food leads to any harm.
    ii. Dermal exposure. Residues of nucleic acids that are part of a
plant-incorporated protectant may in some cases be present in sap or
other exudates from the plant or the food, and, thus, may present some
limited opportunity for dermal exposure to persons coming physically
into contact with the plant or raw agricultural food from the plant.
Individuals preparing meals are those most likely to experience dermal
contact with the residues on a non-occupational basis. However, on a
per person basis, the potential amounts involved in these exposures are
likely to be negligible in comparison to potential exposure through the
dietary route. Moreover, nucleic acids as they occur in food are
unlikely to cross the barrier provided by the skin (Refs. 22 and 23).
This is particularly true for residues of nucleic acids that are part
of a plant-incorporated protectant as these nucleic acids, for the most
part, exist in the plant as polymers (Refs. 22 and 23).
    iii. Inhalation exposure. Residues of nucleic acids that are part
of a plant-incorporated protectant may be present in pollen, and some
individuals (e.g., those near enough to farms, nurseries or other
plant-growing areas to be exposed to wind-blown pollen, or visiting
such areas) may be exposed, through inhalation, to the pollen. On a per
person basis, the potential amounts of pollen involved in these
exposures are likely to be negligible in comparison to potential
exposure through the dietary route. It is unlikely that exposure to the
pollen is equivalent to exposure to residues of nucleic acids that are
part of a plant-incorporated protectant. In pollen, residues of nucleic
acids will likely be integrated into the tissue of the pollen grain.
Pollen grains are solid, insoluble particles of sufficiently large
diameter that they are filtered out in the nasopharynx or in the upper
respiratory tract (Refs. 23 and 24). Pollen grains containing residues
that are the subject of this exemption are unlikely to cross the
barrier provided by the mucous membrane of the respiratory tract (Refs.
23 and 24) and thus exposure through this route is not likely to be
additive to dietary exposure of nucleic acids (Refs. 23 and 24).
    iv. Drinking water. EPA also evaluated potential non-occupational
exposures in drinking water. Residues of nucleic acids that are part of
a plant-incorporated protectant are produced inside the plant itself.
Nucleic acids, and residues of nucleic acids, are an integral part of
the living tissue of the plant. When the plant dies or a part is
removed from the plant, microorganisms colonizing the tissue
immediately begin to degrade it, using the components of the plant
tissue (including residues of nucleic acids that are part of a plant-
incorporated protectant) as building blocks for making their own
cellular components or for fueling their own metabolisms (Ref. 21).
Nucleic acids that are part of a plant-incorporated protectant are
subject to the same processes of biodegradation and decay that all
biotic materials undergo (Ref. 21) . This turnover of biotic materials
in nature through a process of biodegradation occurs fairly rapidly. In
addition, nucleic acids are, for the most part, highly unstable outside
of the cellular environment and are usually very quickly broken down
(Refs. 3 and 21). Because of the very rapid turnover of these residues,
even if they reach surface waters (e.g., through plant parts falling
into bodies of water), they are unlikely to present anything other than
a very negligible exposure in drinking water drawn either from surface
or ground water sources.
    v. Residential exposure. EPA is not aware of any residential uses
of plant-incorporated protectants that might result in exposure to
residues of nucleic acids that are part of a plant-incorporated
protectant.
    7. Sensitivities of subgroups. EPA considered available information
on the sensitivities of subgroups as it pertains to residues of nucleic
acids that are part of a plant-incorporated protectant. As nucleic
acids are ubiquitous in food, are not known to cause any adverse health
effects when consumed in food and are not toxic, EPA does not expect
that one subgroup would be more sensitive than another to residues of
nucleic acids that are part of a plant-incorporated protectant.
    8. Estrogenic or other endocrine effects. Based on available
information concerning their structure and mode of action, plus the
fact that nucleic acids are ubiquitous in foods and have no known
adverse effects when consumed as part of the diet, EPA does not expect
residues of nucleic acids that are part of a plant-incorporated
protectant to cause estrogenic or other endocrine effects. No comment
was received indicating that nucleic acids might have estrogenic or
other endocrine effects in response to the specific request for such
information in the May 16, 1997, supplemental document (62 FR 27142).
If EPA becomes aware of a potential for estrogenic or endocrine effects
from exposure to nucleic acids that are part of a plant-incorporated
protectant, the Agency will reexamine this tolerance exemption in light
of that information.
    9. Safety factors. EPA did not rely solely on available animal data
in reaching its determination that residues of nucleic acids that are
part of a plant-incorporated protectant can be exempted from the
requirement of a tolerance. There is a long history of safe human
consumption of nucleic acids in

[[Page 37827]]

food derived from plants and from animals that consume forage and other
crops (e.g., corn and other grains) containing nucleic acids. EPA thus
was able to rely on epidemiological studies on humans (Refs. 5, 6, 7,
8, 9, 10, 11, 12, and 13) and a century of systematic scientific study
of the constituents of food available in the public literature (Ref.
4). EPA also relied on knowledge in plant genetics, plant physiology,
phytopathology, microbial ecology, ecology, biochemistry and plant
breeding. EPA believes that long-term evidence of human consumption and
the associated information base (Refs. 4, 5, 6, 7, 8, 9, 10, 11, 12,
and 13), with a more limited reliance on animal experimentation data,
are the appropriate information base for this exemption. Because the
EPA was able to rely on data from humans, the Agency concluded that a
safety factor designed to account for uncertainties in extrapolating
from animal data would not be necessary. Because the available
epidemiological and other information generated on humans was based on
studies employing very large numbers of individuals, the Agency
concluded that aten-fold safety factor to account for uncertainties in
analyzing the human data would not be necessary.
    10. Infants and children. EPA considered available information on
consumption patterns of infants and children, including special
sensitivity, cumulative effects of residues of nucleic acids that are
part of a plant-incorporated protectant with other substances that may
have a common mechanism of toxicity with these residues, and the need
for a margin of safety for infants and children.
    i. Dietary consumption patterns. EPA considered available
information on the dietary consumption pattern of infants and children
as it pertains to residues in food of nucleic acids that are part of a
plant-incorporated protectant. The range of foods consumed by infants
and children is in general more limited than the range of foods
consumed by adults. Most newborns rely on milk products for nutrition,
although some infants are fed soy-based products. Infants begin as
early as four months of age to consume specific types of solid foods.
Subsequent to four months of age, apart from processing to facilitate
swallowing, the diets of infants begin to be based on foods consumed by
the general adult population albeit in different proportions. As
infants and children mature, more and more of the foods normally
consumed by adults become part of their diets, and the relative
proportions of the different types of food consumed changes to more
closely resemble an adult diet. All foods consumed by infants and
children, including milk and soy-based products, contain nucleic acids
as do all foods consumed by adults. Since nucleic acids are ubiquitous
in food, from the products infants consume after birth through the
changing diets children consume as they mature, EPA concluded that
infants and children have been, and are, exposed to nucleic acids as
part of their diet. Although the diets of humans change from infancy
through childhood and into adulthood, there is no evidence that such
changes are likely to result in disproportionately high consumption of
residues of nucleic acids, among infants and children in comparison to
the general population. Nucleic acids in food are not toxic and there
is no evidence that exposure to nucleic acids in food, including
changes in exposure because of changes in the relative proportions of
the different types of food consumed from infancy through childhood and
into adulthood, leads to any harm.
    ii. Special susceptibility. EPA considered available information on
the potential for special susceptibility of infants and children,
including pre-natal and post-natal toxicity, to residues of nucleic
acids that are part of a plant-incorporated protectant. Nucleic acids
in food are not toxic and there is no scientific evidence that nucleic
acids as a component of food would have a different effect on children,
in light of neurological differences between infants and children and
adults, than they would on the adult population.
    iii. Cumulative effects of residues with other substances with a
common mechanism of toxicity. EPA examined the available information on
the cumulative effect of residues of nucleic acids that are part of a
plant-incorporated protectant as well as other substances in food that
may have a common mechanism of toxicity. The Agency's consideration of
the effects of the residues of nucleic acids that are part of a plant-
incorporated protectant on the general population also included
consideration of effects on infants and children. Nucleic acids are not
toxic when consumed as part of the diet, and EPA is not aware of
substances that might have a common mechanism of toxicity with nucleic
acids. There is no evidence indicating that adverse effects on infants
and children due to aggregate exposure to residues of nucleic acids and
other substances could occur.
    iv. Margin of safety. In determining whether the residues of
nucleic acids that are part of a plant-incorporated protectant are
safe, FFDCA section 408(b)(2)(C) directs EPA to apply a tenfold margin
of safety for the residues and other sources of exposure to infants and
children to account for potential prenatal and postnatal toxicity and
completeness of data on threshold effects with respect to exposure and
toxicity to infants and children, unless a different margin will be
safe. For residues of nucleic acids that are part of a plant-
incorporated protectant, EPA has determined that a tenfold margin of
safety is not necessary to protect infants and children. EPA reaches
this determination based on reliable, valid and complete information.
As noted in other sections of Unit IX., EPA based its assessment of
exposure and toxicity upon the long history of safe human consumption
of food containing nucleic acids from plants, and other animals that
consume plants containing nucleic acids, and other substances in food
that may have a common mechanism of toxicity (Ref. 4), and associated
epidemiological and other studies (Refs. 4, 5, 6, 7, 8, 9, 10, 11, 12,
and 13). EPA also relied upon information from the disciplines of plant
genetics, plant physiology, phytopathology, microbial ecology, ecology,
biochemistry and plant breeding. Based on all of this information, EPA
concludes that nucleic acids in food are not toxic and may be safely
consumed, including by infants and children. There is no evidence that
exposure to nucleic acids in food, including changes in exposure
because of differences in the relative proportions of the different
types of food consumed from infancy through childhood and into
adulthood, leads to any harm. Thus, on the basis of valid, complete and
reliable information, EPA has concluded that nucleic acids in food are
safe for infants and children, and that a margin of safety need not be
applied for residues in food of nucleic acids that are part of a plant-
incorporated protectant.
    11. Analytical methods. EPA has decided that even though
methodology exists to detect and measure the amount of nucleic acids in
food and to detect and measure the residues of nucleic acids that are
part of a plant-incorporated protectant (Ref. 4), there is no need to
employ a practical method for detecting and measuring the levels of
such residues. The effect of nucleic acids on humans was assessed in
light of the known presence of nucleic acids in all foods (Refs. 3 and
4), the long history of safe human consumption of plant food containing
nucleic acids, i.e., food derived from crop plants and from animals
that consume forage and other crops containing nucleic acids, and
associated epidemiological and other studies (Refs. 4, 5, 6, 7, 8, 9,
10, 11, 12,

[[Page 37828]]

and 13). EPA combined this information with knowledge from the
disciplines of plant genetics, plant physiology, phytopathology,
microbial ecology, ecology, biochemistry and plant breeding. Nucleic
acids in foods do not have a toxic effect and cause no adverse effects
to humans. There is no reason to believe that nucleic acids that are
part of a plant-incorporated protectant would behave any differently
than all of the other nucleic acids in food. There is a reasonable
certainty that no harm will result from exposure to any amount of
residues of nucleic acids that are part of a plant-incorporated
protectant in food. Because these residues may be present in food at
any level without causing harm, EPA has concluded that an analytical
method is not required for detecting and measuring the levels in food
of the residues of nucleic acids that are part of a plant-incorporated
protectant. EPA consulted with the Department of Health and Human
Services (DHHS) in developing the proposed exemption and in issuing
this final rule for residues of nucleic acids that are part of a plant-
incorporated protectant.

C. Determination of Safety for United States Population, and Infants
and Children

    Based on the information discussed in this document and that
discussed in the 1994 Federal Register documents and the supplemental
documents and the record as described in Unit X., EPA concludes that
there is a reasonable certainty that no harm will result to the United
States population in general, and to infants and children in the United
States, from aggregate exposure to residues of nucleic acids that are
part of a plant-incorporated protectant, including all anticipated
dietary exposures and all other exposures for which there is reliable
information. Under this exemption from the requirement for a tolerance,
EPA exempts residues of nucleic acids that are part of a plant-
incorporated protectant. Nucleic acids are normally a component of food
from plants. Extensive use and experience show the safety of foods
containing nucleic acids. The many years of human experience with the
growing, preparing and consuming food from plants containing nucleic
acids and information generated through years of study of the food
supply (Refs. 4, 5, 6, 7, 8, 9, 10, 11, 12, and 13), indicate that
adverse effects due to aggregate exposure through the dietary, non-food
oral, dermal and inhalation routes are highly unlikely.

X. Documents in the Official Record

    As indicated in Unit I.B.2., the official record for this final
rule has been established under docket control number OPP-300371B, the
public version of which is available for inspection as specified in
Unit I.B.2.

A. References

    The following books, articles and reports were used in preparing
this final rule and were cited in this document by the number
indicated:
    1. Whittaker, R. H. 1969. New concepts of kingdoms of organisms.
Science, 163:150-160.
    2. Environmental Protection Agency (EPA). 2000. Summary of public
comments and EPA response on issues associated with plant-incorporated
protectants (formerly plant-pesticides) for dockets OPP-300371 and OPP-
300371A.
    3. Goodwin, T. W. and E. I. Mercer. 1983. Introduction to Plant
Biochemistry. Pergamon Press. Oxford, New York, Toronto, Sydney, Paris,
Frankfurt.
    4. International Food Biotechnology Council. 1990. Biotechnologies
and food; Assuring the safety of foods produced by genetic
modification. In: Regulatory Toxicology and Pharmacology. Volume 12.
Academic Press, Inc. New York, New York.
    5. World Cancer Research Fund and American Institute for Cancer
Research. 1997. Food, Nutrition and the Prevention of Cancer: A Global
Perspective. BANTA Book Group, Menasha, Wisconsin.
    6. Lampe, J. M. 1999. Health effects of vegetables and fruit:
assessing mechanisms of action in human experimental studies. American
Journal of Clinical Nutrition. Sep;70(3 Suppl):475S-490S.
    7. Ogomoto, I. A. Shibata and K. Fukuda. 2000. World Cancer
Research Fund/American Institute of Cancer Research 1997
recommendation: applicability to digestive tract cancer in Japan.
Cancer Causes Control Jan;11(1):9-23.
    8. Joseph, J. A., B. Shukitt-Hale, N. A. Denisova, D. Bielinski, A.
Martin, J. J. McEwen and P. C. Bickford. 1999. Reversals of age-related
declines in neuronal signal transduction, cognitive, and motor
behavioral deficits with blueberry, spinach, or strawberry dietary
supplementation. Journal of Neuroscience. Sep 15;19(18):8114-21.
    9. Segasothy, M. And P. A. Phillips. 1999. Vegetarian diet: panacea
for modern lifestyle diseases? QJM Monthly Journal of the Association
of Physicians Sep;92(9):531-44.
    10. Joshipura, K. J., A. Ascherio, J. E. Manson, M. J. Stampfer, E.
B. Rimm, F. E. Speizer, C. H. Hennekens, D. Spiegelman and W. C.
Willett. 1999. Fruit and vegetable intake in relation to risk of
ischemic stroke. Journal of the American Medical Association.
Oct6;282(13)1233a-9.
    11. Thompson, H. J., J. Heimendinger, A. Haegele, S. M. Sedlacek,
C. Gillette, C. O'Neill, P. Wolfe and C. Conry. 1999. Effect of
increased vegetable and fruit consumption on markers of oxidative
cellular damage. Carcinogenesis Dec;20(12):2261-6.
    12. New, S. A., S. P. Robins, M. K. Campbell, J. C. Martin, M. J.
Garton, C. Boltin-Smith, D. A. Grubb, S. J. Lee and D. M. Reid. 2000.
Dietary influences on bone mass and bone metabolism: further evidence
of a positive link between fruit and vegetable consumption and bone
health? American Journal of Clinical Nutrition. Jan;71(1):142-51.
    13. Michaud, D. S., D. Spiegelman, S. K. Clinton, E. B. Rimm, W. C.
Willett and E. L. Giovannucci. 1999. Fruit and vegetable intake and
incidence of bladder cancer in a male prospective cohort. Journal of
the National Cancer Institute. Apr7;91(7):605-13.
    14. EPA issue paper. 1994. FIFRA: Benefit and environmental risk
considerations for inherent plant-pesticides.
    15. Agrios, George. 1988. Plant Pathology. Third Edition. Academic
Press. New York, New York.
    16. Principles and Practice of Infectious Diseases. 1979. Edited by
G. L. Mandell, R. G. Douglas, Jr. and J. E. Bennett. John Wiley and
Sons, New York.
    17. Raven, P. H., R. F. Evert, and S. E. Eichhorn. 1992. Biology of
Plants. Fifth Edition. Worth Publishers, New York, New York.
    18. Environmental Protection Agency (EPA). Meeting of the EPA
Biotechnology Science Advisory Committee (BSAC); Subcommittee on plant-
pesticides. July 13, 1993. Final Report.
    19. Hayden, F. G. 1996. Antiviral agents. In: Goodman and Gilmans's
The Pharmacological Basis of Therapeutics. Ninth Edition. Edited by J.
G. Hardman, L. E. Limbird, P. B. Molinoff, and R. W. Rudden. McGraw-
Hill Health Profession Division. New York, New York.
    20. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of
Human Poisoning. 1997. Second Edition. M. J. Ellenhorn, S. Schonwald,
G. Ordog, J. Wasserberger. Williams and Wilkins. Baltimore, Maryland.
    21. Atlas, R. and R. Bartha. 1987. Microbial Ecology. Benjamin/
Cummings

[[Page 37829]]

Publishing Company, Inc. Menlo Park, California.
    22. Guy, R. H., and J. Hadgraft. 1991. Principles of skin
permeability relevant to chemical exposure. In: Dermal and Ocular
Toxicology: Fundamentals and Methods. Edited by D. W. Hobson. CRC Press
Boca Raton, Florida.
    23. Environmental Protection Agency (EPA) issue paper. 2000. Dermal
and inhalation exposure to plant substances.
    24. Environmental Protection Agency. 1997. Exposure Factors
Handbook. Volume 1. National Center for Environmental Assessment. EPA/
600/P-95/002Fa.
    25. Environmental Protection Agency (EPA). 2000. Economic analysis
of the plant-incorporated protectant regulations under the Federal
Insecticide, Fungicide, and Rodenticide Act.

B. Additional Information

    The complete official record for this rulemaking includes:
    The docket identified by the docket control number OPP-300370 for
the document entitled ``Proposed Policy; Plant-Pesticides Subject to
the Federal Insecticide, Fungicide, and Rodenticide Act and the Federal
Food, Drug, and Cosmetic Act'' (59 FR 60496, November 23, 1994) (FRL-
4755-2).
    The docket identified by the docket control number OPP-300369 for
the document entitled ``Plant-Pesticides Subject to the Federal
Insecticide, Fungicide and Rodenticide Act; Proposed Rule'' (59 FR
60519, November 23, 1994) (FRL-4755-3).
    The docket identified by the docket control number OPP-300368 for
the document entitled ``Plant-Pesticides; Proposed Exemption From the
Requirement of a Tolerance Under the Federal Food, Drug, and Cosmetic
Act'' (59 FR 60535, November 23, 1994) (FRL-4758-8).
    The docket identified by the docket control number OPP-300371 for
the document entitled ``Plant-Pesticides; Proposed Exemption From the
Requirement of a Tolerance Under the Federal Food, Drug, and Cosmetic
Act for Nucleic Acids Produced in Plants'' (59 FR 60542, November 23,
1994) (FRL-4755-5).
    The docket identified by the docket control number OPP-300367 for
the document entitled ``Plant-Pesticides; Proposed Exemption From the
Requirement of a Tolerance Under the Federal Food, Drug, and Cosmetic
Act for Viral Coat Protein Produced in Plants'' (59 FR 60545, November
23, 1994) (FRL-4755-4).
    The docket identified by the docket control number OPP-300370A for
the document entitled ``Plant-Pesticide Subject to the Federal
Insecticide, Fungicide, and Rodenticide Act and the Federal Food, Drug,
and Cosmetic Act; Reopening of Comment Period'' (61 FR 37891, July 22,
1996) (FRL-5387-4).
    The docket identified by the docket control number OPP-300368A for
the document entitled ``Plant-Pesticides; Supplemental Notice of
Proposed Rulemaking'' (62 FR 27132, May 16, 1997) (FRL-5717-2).
    The docket identified by the docket control number OPP-300371A for
the document entitled ``Plant-Pesticides; Nucleic Acids; Supplemental
Notice of Proposed Rulemaking'' (62 FR 27142, May 16, 1997) (FRL-5716-
7).
    The docket identified by the docket control number OPP-300367A for
the document entitled ``Plant-Pesticides; Viral Coat Proteins;
Supplemental Notice of Proposed Rulemaking'' (62 FR 27149 May 16, 1997)
(FRL-5716-6).
    The docket identified by the docket control number OPP-30069A for
the document entitled ``Plant-Pesticides, Supplemental Notice of
Availability of Information'' (64 FR 19958 April 23, 1999) (FRL-6077-
6).
    The docket identified by the docket control number OPP-300368B for
the companion document entitled ``Exemption From the Requirement of a
Tolerance Under the Federal Food, Drug, and Cosmetic Act for Residues
Derived Through Conventional Breeding From Sexually Compatible Plants
of Plant-Incorporated Protectants (Formerly Plant-Pesticides)'' (FRL-
6057-6) published elsewhere in this issue of the Federal Register.
    The docket identified by the docket control number OPP-300369B for
the document entitled ``Regulations Under the Federal Insecticide,
Fungicide, and Rodenticide Act for Plant-Incorporated Protectants
(Formerly Plant-Pesticides)'' (FRL-6057-7) published elsewhere in this
issue of the Federal Register, and the docket identified by the docket
control number OPP-300370B for the document entitled ``Plant-
Incorporated Protectants; Supplemental Notice of Availability of
Information'' (FRL-6760-4).
    Also included in the complete official public record are:
    1. Public comments submitted in response to the proposals and
supplemental documents cited in the above paragraph.
    2. Reports of all meetings of the Biotechnology Science Advisory
Committee and the FIFRA Science Advisory Panel pertaining to the
development of this final rule.
    3. The Economic Analysis (EA) on FIFRA regulations for plant-
incorporated protectants, and documents supporting the EA (Ref. 25).
    4. Support documents and reports.
    5. Records of all communications between EPA personnel and persons
outside EPA pertaining to the final rule. (This does not include any
inter-agency and intra-agency memoranda, unless specifically noted in
the Indices of the dockets).
    6. Published literature that is cited in this document.
    7. The response to comments document pertaining to the development
of this final rule (Ref. 2).

XI. Regulatory Assessment Requirements

    This final rule establishes an exemption from the tolerance
requirement under FFDCA section 408 and does not impose any other
regulatory requirements. As such, the Office of Management and Budget
(OMB) has exempted these types of actions from review under Executive
Order 12866, entitled Regulatory Planning and Review (58 FR 51735,
October 4, 1993).
    This action does not contain any information collections subject to
OMB approval under the Paperwork Reduction Act (PRA), 44 U.S.C. 3501 et
seq., nor does it require OMB review or any Agency action under
Executive Order 13045, entitled Protection of Children from
Environmental Health Risks and Safety Risks (62 FR 19885, April 23,
1997).
    This action does not require any special considerations under
Executive Order 12898, entitled Federal Actions to Address
Environmental Justice in Minority Populations and Low-Income
Populations (59 FR 7629, February 16, 1994), nor does it involve any
technical standards that would require Agency consideration of
voluntary consensus standards pursuant to section 12(d) of the National
Technology Transfer and Advancement Act of 1995 (NTTAA), Public Law
104-113, section 12(d) (15 U.S.C. 272 note).
    This action does not impose any enforceable duty or contain any
unfunded mandate, and will not otherwise significantly or uniquely
affect small governments as described under Title II of the Unfunded
Mandates Reform Act of 1995 (UMRA) (Public Law 104-4).This rule does
not significantly or uniquely affect the communities of Indian trial
governments, nor does it involve or impose any requirements that affect
Indian Tribes. Accordingly, the requirements of section 3(b) of
Executive Order 13084, entitled Consultation and Coordination with

[[Page 37830]]

Indian Tribal Governments (63 FR 27655, May 19, 1998), do not apply to
this rule. Executive Order 13175, entitled Consultation and
Coordination with Indian Tribal Governments (65 FR 67249, November 6,
2000), which took effect on January 6, 2001, revokes Executive Order
13084 as of that date. EPA developed this rulemaking, however, during
the period when Executive Order 13084 was in effect; thus, EPA
addressed tribal considerations under Executive Order 13084. For the
same reasons stated for Executive Order 13084, the requirements of
Executive Order 13175 do not apply to this rule either. For the same
reasons, this rule does not have any substantial direct effect on
States, on the relationship between the national government and the
States, or on the distribution of power and responsibilities among the
various levels of government, as specified in Executive Order 13132,
entitled Federalism (64 FR 43255, August 10, 1999). This rule directly
regulates growers, food processors, food handlers and food retailers,
not States. This action does not alter the relationships or
distribution of power and responsibilities established by Congress in
the preemption provisions of FFDCA section 408(n)(4).
    Pursuant to section 605(b) of the Regulatory Flexibility Act (RFA)
(5 U.S.C. 601 et seq.), the Agency hereby certifies that this final
rule will not have a significant economic impact on a substantial
number of small entities. The Agency's determination is based on the
fact that an exemption from the requirement of a tolerance under FFDCA
section 408, such as that contained in this rule, will not adversely
affect any small businesses. Additional information about the Agency's
determination may be found in the small entity impact analysis prepared
as part of the economic analysis for the FIFRA rulemaking, which is
available in the public version of the official record (Ref. 25). The
Agency has also previously assessed whether establishing tolerances,
exemptions from tolerances, raising tolerance levels or expanding
exemptions might adversely impact small entities and concluded, as a
general matter, that there is no adverse economic impact associated
with these actions. See 46 FR 24950, May 4, 1981.
    This rule is not subject to Executive Order 13211, entitled Actions
Concerning Regulations That Significantly Affect Energy Supply,
Distribution, or Use (66 FR 28355, May 22, 2001), because this action
is not expected to affect energy supply, distribution, or use.

XII. Submission to Congress and the Comptroller General

    The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the
Small Business Regulatory Enforcement Fairness Act of 1996, generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report, which includes a copy of the rule,
to each House of the Congress and to the Comptroller General of the
United States. EPA will submit 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 United States prior
to publication of this final rule in the Federal Register. This final
rule is not a ``major rule'' as defined by 5 U.S.C. 804(2).

List of Subjects in 40 CFR Part 174

    Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Plants, Reporn the public version of the official record (Ref. 25). The
Agency has also previously assessed whether establishing tolerances,
exemptions from tolerances, raising tolerance levels or expanding
exemptions might adversely impact small entities and concluded, as a
general matter, that there is no adverse economic impact associated
with these actions. See 46 FR 24950, May 4, 1981.
    This rule is not subject to Executive Order 13211, entitled Actions
Concerning Regulations That Significantly Affect Energy Supply,
Distribution, or Use (66 FR 28355, May 22, 2001), because this action
is not expected to affect energy supply, distribution, or use.

XII. Submission to Congress and the Comptroller General

    The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the
Small Business Regulatory Enforcement Fairness Act of 1996, generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report, which includes a copy of the rule,
to each House of the Congress and to the Comptroller General of the
United States. EPA will submit 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 United States prior
to publication of this final rule in the Federal Register. This final
rule is not a ``major rule'' as defined by 5 U.S.C. 804(2).

List of Subjects in 40 CFR Part 174

    Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Plants, Reporting and
recordkeeping requirements.

    Dated: July 12, 2001.
Christine T. Whitman,
Administrator.

    Therefore, 40 CFR chapter I is amended as follows:

PART 174--[AMENDED]

    1. The authority citation for part 174 continues to read as
follows:

    Authority: 7 U.S.C. 136-136y and 21 U.S.C. 346a and 371.

    2. Section 174.475 is added to subpart W to read as follows:

Sec. 174.475  Nucleic acids that are part of a plant-incorporateic acids that are part of a plant-incorporated
protectant; exemption from the requirement of a tolerance.

    Residues of nucleic acids that are part of a plant-incorporated
protectant are exempt from the requirement of a tolerance.

[FR Doc. 01-17982 Filed 7-16-01; 11:45 am]
BILLING CODE 6560-50-S