[Federal Register: July 19, 2001 (Volume 66, Number 139)]
[Rules and Regulations]
[Page 37771-37817]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr19jy01-19]

[[Page 37771]]

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Part IV

Environmental Protection Agency

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40 CFR Parts 152 and 174

Plant-Incorporated Protectants; Final Rules and Proposed Rule

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Parts 152 and 174

[OPP-300369B; FRL-6057-7]
RIN 2070-AC02


Regulations Under the Federal Insecticide, Fungicide, and
Rodenticide Act for 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,
repelling or mitigating any pest.'' In this rule, EPA finalizes certain
of the proposed rules published in 1994, 1996, and 1997. Specifically,
EPA changes the name of this type of pesticide from ``plant-pesticide''
to ``plant-incorporated protectant''; clarifies the relationship
between plants and plant-incorporated protectants under FIFRA; exempts
from FIFRA requirements plant-incorporated protectants derived through
conventional breeding from sexually compatible plants; and establishes
a new part in the Code of Federal Regulations (CFR) specifically for
plant-incorporated protectants. Procedures are also set forth for
Confidential Business Information (CBI); any claim of confidentiality
must be substantiated when the claim is made. This rule will benefit
the public by ensuring that public health and the environment are
adequately protected while reducing burden on the regulated community,
thereby potentially reducing costs for consumers.

DATES: This rule is effective September 17, 2001.

FOR FURTHER INFORMATION CONTACT: Philip Hutton, Biopesticides and
Pollution Prevention Division, Office of Pesticide Programs (7511C),
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460; telephone number: (703) 308-8260; e-mail address:
hutton.phil@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action 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
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 in
 the life sciences                                  conducting research
                                                    in the physical,
                                                    engineering, or life
                                                    sciences, such as
                                                    agriculture and
                                                    biotechnology
------------------------------------------------------------------------

    This table is not intended to be exhaustive, but rather provides a
guide for readers regarding the types of entities potentially affected
by this action. Other types of entities not listed in the table could
also be affected. The North American Industrial Classification System
(NAICS) 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 provisions in 40 CFR part 174.
If you have any questions regarding 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 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 the docket control number OPP-300369B. 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, which includes
printed, paper versions of any electronic comments submitted during an
applicable comment period, is available for inspection in the Public
Information and Record Integrity Branch (PIRIB), Rm. 119, Crystal Mall
#2, 1921 Jefferson Davis Highway, 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.

II. Under What Authority Is EPA Issuing The Rule?

A. FIFRA

    This rule is promulgated under the authority of FIFRA section 3 and
section 25(a) and (b) (7 U.S.C. 136a and 136w(a) and (b)) and FFDCA
section 346a and 371.
    FIFRA section 3(a) provides, with some exceptions, that no person
may distribute or sell in the United States any pesticide that is not
registered

[[Page 37773]]

under the Act (7 U.S.C. 136a(a)). 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)).
    Although FIFRA requires the registration of most pesticides, it
also authorizes the regulation of unregistered pesticides. FIFRA
section 3(a) provides that, to the extent necessary to prevent
unreasonable adverse effects on the environment, the Administrator may
limit the distribution, sale, or use of any pesticide that is not
registered under section 3 of FIFRA, or subject to an experimental use
permit under section 5 of FIFRA, or subject to an emergency exemption
under section 18 of FIFRA (7 U.S.C. 136a(a)). Pesticides that are ``not
registered'' include pesticides that are exempt from FIFRA requirements
under section 25(b).
    Before EPA may register a pesticide under FIFRA, the applicant must
show that the pesticide ``when used in accordance with widespread and
commonly recognized practice, . . . will not generally cause
unreasonable adverse effects on the environment'' (7 U.S.C.
136a(c)(5)). The term ``environment'' includes ``water, air, land, and
all plants and man and other animals living therein, and the
interrelationships which exist among these'' (7 U.S.C. 136(j)). FIFRA
section 2(bb) defines the term ``unreasonable adverse effects on the
environment'' to mean: ``(1) any unreasonable risk to man or the
environment, taking into account the economic, social, and
environmental costs and benefits of the use of any pesticide, or (2) a
human dietary risk from residues that result from a use of a pesticide
in or on any food inconsistent with the standard under section 408 of
the Federal Food, Drug, and Cosmetic Act'' (7 U.S.C. 136(bb)).
    When EPA published its proposed rules and policy for plant-
incorporated protectants in 1994, the FIFRA definition of
``unreasonable adverse effects'' contained only the first criterion of
unreasonable risk to man or the environment. Subsequently, Congress
enacted the Food Quality Protection Act (FQPA) in 1996, and expanded
the FIFRA definition of ``unreasonable adverse effects on the
environment'' by adding the second criterion of consistency with the
standard under section 408 of the Federal Food, Drug, and Cosmetic Act
(FFDCA) (Public Law 104-170 (August 3, 1996)). As a result of this
change, a pesticide must meet both criteria of the unreasonable adverse
effects test to qualify for registration. In the case of a pesticide
whose use would not result in residues in or on food, the second
criterion would not apply. Once a pesticide has been registered, it may
be sold and distributed in the United States.
    Section 25(b)(2) of FIFRA allows EPA to exempt, by regulation, any
pesticide from some or all of the requirements of FIFRA, if the
pesticide is of a character which is unnecessary to be subject to FIFRA
in order to carry out the purposes of that Act (7 U.S.C. 136w(b)(2)).
EPA interprets FIFRA section 25(b)(2) to authorize EPA to exempt a
pesticide or category of pesticides that EPA determines poses a low
probability of risk to the environment, and that is not likely to cause
unreasonable adverse effects to the environment even in the absence of
regulatory oversight under FIFRA.
    To determine whether a pesticide qualifies for an exemption under
section 25(b)(2), EPA evaluates both the potential risks and benefits
of the use of the pesticide. In evaluating a pesticide under the first
exemption criterion, whether use of the pesticide poses a low
probability of risk to the environment, EPA considers the extent of the
potential risks caused by use of the pesticide to the environment,
including humans and other animals, plants, water, air and land.
Potential risks to humans include dietary risks as well as non-dietary
risks such as those resulting from occupational or residential exposure
to the pesticide. EPA uses the FFDCA section 408 standard in evaluating
dietary risks as discussed in Unit II.B. EPA will not exempt pesticides
under section 25(b)(2) that fail the low probability of risk criterion.
    In evaluating a pesticide under the second exemption criterion,
whether the use of the pesticide is likely to cause unreasonable
adverse effects on the environment even in the absence of regulatory
oversight under FIFRA, EPA balances all the potential risks to human
health, including any dietary risks (see Unit II.B. for a discussion of
the relationship between this finding and section 408 of the FFDCA),
and risks to the remainder of the environment from use of the pesticide
against the potential benefits associated with its use. In balancing
risks and benefits, EPA considers the economic, social, and
environmental costs and benefits of the use of the pesticide. If the
pesticide meets both exemption criteria, EPA may exempt the pesticide
from regulation under FIFRA section 25(b)(2).

B. Relationship of FIFRA Exemptions to the FFDCA Section 408 Standard

    Under FFDCA section 408(a), a pesticide chemical residue in or on
food is not safe unless EPA has issued either: A tolerance for the
residue and the residue is within the tolerance limits, or an exemption
from the requirement of a tolerance for the residue (21 U.S.C.
346a(a)(1)). FFDCA section 408 authorizes EPA to determine a residue is
safe and exempt from the requirement of a tolerance if the
Administrator ``. . . has determined 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)). Section 408 of the FFDCA also directs EPA to
specifically consider harm that may result to infants and children as a
result of pesticide chemical residues. For additional discussion of
this standard, see the exemptions from the FFDCA requirement of a
tolerance published elsewhere in this issue of the Federal Register
(i.e., exemptions for residues of plant-incorporated protectants
derived through conventional breeding from a plant sexually compatible
with the recipient plant, and residues of nucleic acids that are part
of a plant-incorporated protectant).
    EPA uses the FFDCA section 408 safety standard in evaluating
whether a pesticide used in food meets the two FIFRA exemption criteria
with respect to human dietary risk. A pesticide in food qualifies under
the first FIFRA exemption criterion of low probability of human dietary
risk if it meets the FFDCA section 408 standard for an exemption from
the requirement of a tolerance. Such a pesticide also meets the second
FIFRA exemption criterion of no likely unreasonable adverse effects,
with respect to human dietary risks only, if the risks resulting from
use of that pesticide are consistent with the FFDCA section 408
exemption standard, and the potential benefits of use outweigh any
human health risk even in the absence of regulatory oversight.
    A determination that a pesticide chemical meets the safety standard
of section 408(c) of the FFDCA may also be relevant to whether a
pesticide qualifies for a FIFRA section 25(b)(2) exemption with respect
to human health risks arising from other routes of exposure. In

[[Page 37774]]

determining whether a pesticide chemical residue is safe, EPA must
consider ``available information regarding the aggregate exposure
levels of consumers . . . to the pesticide chemical residue and to
other related substances, including dietary exposure under the
tolerance and all other tolerances in effect for the pesticide chemical
residue, and exposures from other non-occupational sources.'' (21
U.S.C. section 346a(b)(2)(D)(vi)). Consequently, a finding that a
pesticide qualifies for a tolerance exemption could also demonstrate
that the pesticide chemical meets the first exemption criterion of low
probability of risk with respect to human health risks arising from
other non-occupational routes of exposure. Such a pesticide also meets
the second FIFRA exemption criterion of no likely unreasonable adverse
effects, with respect to human health risks arising from all non-
occupational exposures, if the risks resulting from use of that
pesticide are consistent with the FFDCA section 408 exemption standard,
and the potential benefits of use outweigh any human health risk even
in the absence of regulatory oversight.
    However, FIFRA does not provide for exemption of a pesticide in
food based solely upon consistency with the FFDCA section 408 exemption
standard. At a minimum, EPA also must evaluate risks arising from
occupational exposure to humans and determine that such risks meet both
exemption criteria. In addition, EPA must evaluate the risks to the
environment from the pesticide and determine both that the pesticide
poses only a low probability of environmental risks, and that use of
the pesticide is not likely to cause any unreasonable adverse effects
on the remainder of the environment in the absence of regulation under
FIFRA.

III. What is the Background for this Rule?

    This final rule establishes certain basic parameters of EPA's
regulatory program under FIFRA for plant-incorporated protectants. In
this rule, EPA defines the scope of products subject to FIFRA
jurisdiction, and identifies the category of products over which it
will exert regulatory oversight. EPA also establishes certain
fundamental definitions to clarify what will be subject to regulation
as a plant-incorporated protectant. The rule also finalizes certain
regulatory procedures specific to plant-incorporated protectants. This
document also provides some guidance on the way in which the Agency
intends to interpret the existing regulations for these products until
it is able to establish additional regulations specific to plant-
incorporated protectants.
    Specifically, the rule clarifies that plants used as biological
control agents remain exempt from FIFRA requirements, but that plant-
incorporated protectants are not. Second, the rule exempts plant-
incorporated protectants derived through conventional breeding from
sexually compatible plants. Third, this final rule establishes a new 40
CFR part 174, specifically for plant-incorporated protectants; any
additional regulations specific to plant-incorporated protectants will
be codified in 40 CFR part 174. The final rule also imposes a
requirement at Sec. 174.71, that any person producing an otherwise
exempt plant-incorporated protectant for sale and distribution, who
obtains any information regarding adverse effects of this otherwise
exempt plant-incorporated protectant on human health or the environment
report that information to EPA. Finally, the rule includes a provision
that any claim of confidentiality must be made at the time of
submission and substantiated at the time the claim is made.

A. What Is a Plant-Incorporated Protectant?

    Plants have evolved, and thus naturally possess, various mechanisms
to resist pests. The mechanisms of resistance can be varied, including,
for example, structural characteristics of the plant, the production of
metabolites that have toxic properties, biochemical cascades resulting
in localized necrosis of plant tissue, or the production of specific
toxic substances in response to pest attack. Humans have for
approximately 10,000 years selected and bred certain plants as sources
of, for example, food, feed, and fiber, and a frequently selected
characteristic was the ability to resist pests. More recently, humans
have developed scientific techniques by which traits from any living
organism, including an ability to resist pests, can be introduced into
a plant. When humans intend to use substances involved in these
mechanisms in plants for ``preventing, destroying, repelling or
mitigating any pest,'' the substances are pesticides under the FIFRA
definition of pesticide, regardless of whether the pesticidal
capability evolved in the plants or was introduced by breeding or
through the techniques of modern biotechnology.
    The genetic material necessary for the production of such a
pesticidal substance also meets the FIFRA statutory definition of a
pesticide. Such genetic material is introduced into a plant with the
intent of ultimately producing a pesticidal effect even though the
genetic material may not, itself, directly affect pests. The pesticidal
substance, along with the genetic material necessary to produce it,
produced and used in living plants, is designated a ``plant-
incorporated protectant'' by EPA.
    Plant-incorporated protectants are primarily distinguished from
other types of pesticides because they are intended to be produced and
used in the living plant. This difference in use pattern dictates in
some instances differences in approach. For example, because the plant-
incorporated protectant is produced by the plant itself and used in the
living plant, exposure considerations in risk assessments may be
different, although as noted in Unit VII.D.2., the risk assessment
framework used for other types of pesticides can be used for plant-
incorporated protectants.

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

    Nonviable plant tissues, organs, or parts that are used as
pesticides, will not be subject to the provisions of this rule, which
will be codified in regulations at 40 CFR part 174. Rather, such
pesticides are subject to the regulations found in 40 CFR parts 150
through 173 and 40 CFR parts 177 through 180. An example of this type
of pesticide would be the powder, produced by drying and grinding
cayenne peppers, dusted on plants to protect them from pests.
    Substances that are isolated from a plant's tissues and then
applied to plants for pest control will not be subject to the
regulations in 40 CFR part 174. Rather these types of pesticides in
formulations such as those for foliar application are subject to
regulations found in 40 CFR parts 150 through 173 and 40 CFR parts 177
through 180. An example of this type of pesticide would be pyrethrum
isolated from chrysanthemum plants, formulated with other ingredients
for foliar application, and sprayed on other plants for pest control.
    Substances that are synthesized will not be subject to the
regulations in 40 CFR part 174. Such pesticides are subject to
regulations found in 40 CFR parts 150 through 173 and 40 CFR parts 177
through 180. An example of this type of pesticide is the herbicide,
atrazine.

C. What is the History of this Rule?

    This rule is an additional step in fully implementing the
``Coordinated Framework for Regulation of

[[Page 37775]]

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 rule.
    In developing its approach to plant-incorporated protectants, EPA
requested advice from two scientific advisory groups at three meetings.
On December 18, 1992, a Subpanel of the FIFRA Scientific Advisory Panel
(SAP) was convened to review a draft proposed policy statement and to
answer a series of scientific questions concerned primarily with EPA's
proposed exemptions under FIFRA. On July 13, 1993, a Subcommittee of
the EPA Biotechnology Science Advisory Committee (BSAC) was convened to
address a series of scientific questions concerned primarily with EPA's
proposed exemptions under the FFDCA. On January 21, 1994, a joint
meeting of the Subpanel of the SAP and the BSAC Subcommittee was
convened to address a series of scientific questions on approaches to
plant-pesticides under both FIFRA and FFDCA. Advice from these
scientific advisory groups was considered in finalizing this 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, and FRL-4755-8) which described
EPA's policy and proposals for plant-pesticides (now called plant-
incorporated protectants) 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
documents; 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
supplemental documents (62 FR 27132, 27142, 27149) (FRL-5716-6, FRL-
5716-7, 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 exemptions from the FFDCA requirement of a
tolerance for two categories of residues relevant to this final rule.
    On April 23, 1999, EPA published a supplemental document in the
Federal Register (64 FR 19958) (FRL-6077-6) soliciting comment on
whether to change the name of this type of pesticide.
    The documents and reports of the meetings described in this unit
are available in the official record for this rule as described in Unit
VIII.

D. Other Federal Agencies

    EPA is the Federal agency primarily responsible for the regulation
ofpesticides. In fulfilling this mission, EPA works closely with the
U.S. Department of Agriculture (USDA) which has responsibilities under
the Plant Protection Act (PPA), and the U.S. Food and Drug
Administration (FDA) which has responsibilities under the FFDCA. EPA,
USDA, and FDA consult and exchange information when such consultation
is helpful in resolving safety questions. The three agencies also
strive for consistency between programs following one of the basic
tenets of the Coordinated Framework for Regulation of Biotechnology (51
FR 23302, June 26, 1986); i.e., that the agencies composing the
Framework adopt consistent approaches, to the extent permitted by the
respective statutory authorities. A consistent approach between
agencies is easier for the regulated community to understand. It is
also more likely to conserve resources as submitters would more likely
be able to use data developed for one agency to meet requirements posed
by another agency for the same or similar products.
    1. USDA. USDA has authority to prevent the introduction and
dissemination of plant pests under the PPA. Before introducing into the
environment a plant that is regulated under either of these statutes,
approval must be obtained from the USDA/Animal Plant Health Inspection
Service (APHIS) unless the plant is exempt from USDA/APHIS regulation.
The USDA regulations use genetic engineering as a criterion for
determining the scope of its regulations (Refs. 1, 2, and 3).
    EPA recognizes that there is a potential for duplicative oversight
with respect to certain issues that may arise in plant-incorporated
protectant decisions. For example, some of the plant-incorporated
protectants not exempted by EPA are also subject to APHIS/USDA
requirements under the PPA. The potential for most plants containing
plant-incorporated protectants to pose weediness concerns is directly
considered by USDA/APHIS under PPA. In its reviews of Petitions for
Determination of Nonregulated Status under regulations at 7 CFR part
340, the potential for weediness, for displacement of native species,
and potential consequences of gene transfer are evaluated by USDA/
APHIS. EPA and USDA/APHIS will continue to consult and collaborate when
reviews of any plant-incorporated protectant indicates reason for
concern over any of these issues. Weediness is generally thought to be
due to a multiplicity of factors. The Agencies will work to coordinate
their analyses of these factors in accordance with their respective
expertise and jurisdiction. EPA's focus in considering these issues is
on the statutory determination on unreasonable adverse effects the
Agency must make with respect to pesticides, rather than on the
engineered plant itself. In particular, these plant-related issues may
potentially impact use patterns of pesticides, which are of relevance
to the Agency. EPA and USDA/APHIS will work together to avoid potential
duplication and inconsistencies.
    2. FDA. FDA is the primary U.S. agency responsible forensuring the
safety of commercial food and food additives. FDA's authority under
FFDCA extends to any nonpesticidal substance that may be introduced
into a new plant variety and that is expected to become a component of
food. Pursuant to FFDCA and the reorganization that created EPA,
pesticides as defined by FIFRA are subject to EPA's regulatory
authority under FFDCA. Recently, FDA announced its intent to propose a
pre-market notification scheme for foods derived from plants modified
through the use of modern biotechnology.

IV. What Are the Key Features of the Proposed Rule?

    The development of this rule consists of a proposed rule that
appeared in the November 23, 1994, Federal Register and four
supplemental documents affecting the final form of the rule (59 FR
60496, 60519, 60535, 60542, and 60545); a supplemental document that
appeared in the July 22, 1996, Federal Register (61 FR 37891), two
supplemental documents that appeared in the May 16, 1997, Federal
Register (62 FR 27132, 27142), and a supplemental document that
appeared in the April 23, 1999, Federal Register (64 FR 19958).

[[Page 37776]]

A. What Are the Key Features of the November 23, 1994, Federal
Register?

    In the November 23, 1994, Federal Register document (59 FR 60519),
EPA proposed to: first, clarify how the exemption at 40 CFR 152.20
relates to plants used as biological control agents and to plant-
incorporated protectants; second, exempt under FIFRA section 25(b)(2),
plant-incorporated protectants that are derived from plants closely
related to the recipient plant, except for a requirement that sellers
or distributors of an otherwise exempt plant-incorporated protectant
submit to EPA any information they may obtain regarding potential
unreasonable adverse effects caused by an exempt plant-incorporated
protectant; and third, establish new part 40 CFR part 174 specifically
for plant-incorporated protectants. This document also contained a
proposed rule on substantiation of any claim of confidentiality at the
time the claim was made.
    1. Clarification of exemption at 40 CFR 152.20; status of plants
used as biological control agents with regard to FIFRA requirements. In
the November 23, 1994, Federal Register document, EPA proposed to amend
40 CFR 152.20 to clarify that plants used as biological control agents
are exempt from FIFRA requirements under section 25(b)(1). The proposed
amendment at 40 CFR 152.20 would also indicate that this exemption does
not apply to plant-incorporated protectants and would refer the reader
to 40 CFR part 174 for regulations, including a listing of exemptions,
on plant-incorporated protectants.
    2. Proposed exemption of plant-incorporated protectants derived
from plants closely related to the recipient plant. In 1994, EPA
described three options for defining when a plant-incorporated
protectant would be exempt because it is derived from plants closely
related to the recipient plant. EPA proposed to exempt plant-
incorporated protectants derived from plants closely related to the
recipient plant based on the rationale that the probability of new
exposures from this group of plant-incorporated protectants is very
low. Option 1, the Agency's preferred option, used sexual
compatibility, including hybridization achieved by wide and bridging
crosses, as a measure of relatedness between plants. Under this option,
plant-incorporated protectants would be exempt from all FIFRA
requirements, except for the adverse effects reporting requirement, if
the genetic material that leads to the production of the pesticidal
substance is derived from plants that are sexually compatible with the
recipient plant and has never been derived from a source that is not
sexually compatible with the recipient plant. Recipient plant was
described as the plant into which the plant-incorporated protectant is
introduced and in which the plant-incorporated protectant is produced.
Sexually compatible, when referring to plants, was described as capable
of forming a viable zygote through the fusion of two gametes including
the use of bridging or wide crosses between plants.
    Option 2 would utilize the rank of genus as the taxonomic standard
for describing closely related plants such that plant-incorporated
protectants derived from plants classified in the same genus as the
recipient plant would be exempt from all FIFRA requirements, except for
the adverse effects reporting requirement. Taxonomy is a system of
orderly classification of organisms according to their presumed natural
relationships. Taxonomy reflects current scientific observations about
phenotypic, and to a certain extent, genotypic, similarities between
organisms.
    Option 3, also an alternative option, would utilize both the
taxonomic rank of genus and sexual compatibility to describe closely
related plants. This option would exempt from all FIFRA requirements,
except for the adverse effects reporting requirement, plant-
incorporated protectants derived from plants classified in the same
genus as the recipient plant, as well as plant-incorporated protectants
derived from plants sexually compatible with the recipient plant. Under
Options 1 and 3, plant-incorporated protectants derived from plants
sexually compatible with the recipient plant would be exempt even if
the source and recipient plants are classified in different genera.
    None of the options offered by the EPA were intended to exempt a
plant-incorporated protectant that has been modified so that it is
significantly different functionally from the plant-incorporated
protectant as it occurs in the source organism (59 FR 60524).
    i. Associated definitions. In 1994, pertinent definitions
associated with the proposed exemptions included:
    ``Bridging crosses between plants'' would be the utilization of an
intermediate plant in a cross to produce a viable zygote between the
intermediate plant and a first plant, in order to cross the plant
resulting from that zygote with a third plant that would not otherwise
be able to produce viable zygotes from the fusion of its gametes with
those of the first plant. The result of the bridging cross is the
mixing of genetic material of the first and third plant through the
formation of an intermediate zygote.
    ``Wide crosses between plants'' would be to facilitate the
formation of viable zygotes through the use of surgical alteration of
the plant pistil, bud pollination, mentor pollen, immunosuppressants,
in vitro fertilization, pre-pollination and post-pollination hormone
treatments, manipulation of chromosome numbers, embryo culture, or
ovary and ovule cultures, or any other technique that the Administrator
determines meets this definition.
    In 1994, EPA also presented a definition for plant-pesticide, now
termed plant-incorporated protectant, and definitions of active and
inert ingredient for plant-pesticides.
    ``Plant-pesticide'' was defined 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.
    ``Active ingredient,'' when referring to plant-incorporated
protectants only, was defined 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.
    ``Genetic material necessary for the production'' was defined as:
Genetic material that encodes for a pesticidal substance or leads to
the production of a pesticidal substance and regulatory regions. It
does not include noncoding, nonexpressed nucleotide sequences.
    ``Inert ingredient,'' when referring to plant-incorporated
protectants only, was defined 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.
    ``Living plant'' was defined as a plant that is alive, including
periods of dormancy, and all viable plant parts/organs involved in the
plant's life cycle.
    ``Noncoding, nonexpressed nucleotide sequences'' were defined as
the nucleotide sequences that are not transcribed and are not involved
in gene expression. Examples of noncoding, nonexpressed nucleotide
sequences include linkers, adapters, homopolymers, and sequences of
restriction enzyme recognition sites.
    ii. Potential exemption criterion based on process. The Agency also
requested

[[Page 37777]]

in the 1994 Federal Register document (50 FR 60514, 60530), comment on
the utility of an exemption criterion based on the process (e.g., rDNA)
used to introduce the plant-incorporated protectant into a plant. In
this approach, plant-incorporated protectants developed through
techniques other than those of modern biotechnology would be exempted,
e.g., those developed through conventional plant breeding would be
exempted. Categories of those plant-incorporated protectants that were
not exempted could subsequently be considered for exemption on the
basis of risk potential.
    iii.Reporting of unreasonable adverse effects for exempted plant-
incorporated protectants. In 1994, EPA proposed to require, under FIFRA
section 3(a), that any person who sells or distributes any otherwise
exempt plant-incorporated protectant, who obtains any information
regarding potential unreasonable adverse effects on human health or the
environment, must within 30 days of receipt of such information submit
the information to EPA. This provision was proposed to enable the
Agency to address unforeseeable events from use of otherwise exempt
plant-incorporated protectants. (This reporting requirement is referred
to, in this preamble, as the ``adverse effects reporting
requirement.'')
    3. Proposed new 40 CFR part 174. In the November 23, 1994, Federal
Register document, EPA proposed to establish a new part in the CFR, 40
CFR part 174, specifically for plant-incorporated protectants.
Establishment of a new part would allow the Agency to consolidate
regulations specifically applicable to plant-incorporated protectants
in one part of the CFR. EPA believed such a consolidation would be
appropriate and justified because of the characteristics that
distinguish plant-incorporated protectants from other types of
pesticides. The proposed consolidation was expected to benefit the
public by providing greater focus, enhanced clarity, and ease of use,
because all the regulations specific for plant-incorporated protectants
would be in one part of title 40. The proposed 40 CFR part 174 would
include, for example, definitions that are generally applicable
throughout part 174, exemptions from FIFRA regulation, and a subpart
for tolerances and exemptions from the requirement of a tolerance
published under FFDCA section 408 for residues of plant-incorporated
protectants.
    4. Proposed rule regarding upfront substantiation of confidential
business information. EPA proposed in 1994 that any claim of
confidentiality would have to be made at the time of submission and
substantiated at the time the claim is made.

B. What Issues Were Discussed in the Supplemental Federal Register
Documents?

    Subsequent to publication of the November 23, 1994 Federal Register
document (59 FR 60519), EPA published four supplemental documents
relevant to this document. These supplemental documents are described
below.
    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 documents; i.e., how the concept of
inert ingredient related to plant-incorporated protectants. In 1994,
EPA stated that an inert ingredient for plant-incorporated 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.''
However, additional information caused EPA to request further public
comment on its treatment of inert ingredients, including whether there
should be inert ingredients for plant-incorporated protectants.
    2. May 16, 1997. In August of 1996, Congress enacted the FQPA which
amended the FFDCA and FIFRA. On May 16, 1997, EPA published in the
Federal Register two supplemental documents (62 FR 27132, 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
tolerance exemptions, and thus, to the proposed exemption of certain
plant-incorporated protectants from FIFRA requirements. These
supplemental documents are discussed in detail in companion documents
published elsewhere in this issue of the Federal Register addressing
tolerance exemptions for pesticide chemical residues derived through
conventional breeding from sexually compatible plants and residues of
nucleic acids that are part of a plant-incorporated protectant.
    3. April 23, 1999. In response to the request that EPA consider
another name for this type of pesticide, the Agency published in the
April 23, 1999 Federal Register (64 FR 19958) a document requesting
comment on the advisability of substituting an alternative name for the
term ``plant-pesticide,'' and requesting appropriate alternative names
for this class of pesticides. EPA also specifically requested comment
on whether the alternative name, ``plant-expressed protectants,'' would
be an acceptable name for this category of pesticides. EPA noted that
if the Agency changed the name of the pesticides termed, ``plant-
pesticides,'' the change would only affect the name. It would not
affect the status of the pesticidal substance or the genetic material
necessary to produce it. The Agency also noted that even with a
different name, these would still be pesticides under FIFRA section
2(u), and a change of name would not affect any regulatory
requirements.

V. What are the Key Features of this Final Rule?

    In this final rule, EPA, first, clarifies that plants used as
biological control agents remain exempt from FIFRA requirements, as
well as clarifying the relationship between plants and plant-
incorporated protectants; second, issues an exemption for a category of
plant-incorporated protectants; and third, establishes a new 40 CFR
part 174, specifically for plant-incorporated protectants. This rule
also imposes a requirement at 40 CFR 174.71 that any person producing,
for sale and distribution an otherwise exempt plant-incorporated
protectant, who obtains any information regarding adverse effects of
this otherwise exempt plant-incorporated protectant on human health or
the environment, report that information to EPA. Finally, the rule
includes a provision that any claim of confidentiality must be made at
the time of submission and substantiated at the time the claim is made.

A. Clarification of Exemption at 40 CFR 152.20; Status of Plants Used
as Biological Control Agents with Regard to FIFRA Requirements

    This final rule amends 40 CFR 152.20 to clarify that plants used as
biological control agents remain exempt from FIFRA regulation, but
plant-incorporated protectants will be subject to the requirements of
FIFRA unless otherwise exempted. The final rule also refers the reader
to 40 CFR part 174 for regulations, including a list of exemptions, on
plant-incorporated protectants.

B. Exemption of Plant-Incorporated Protectants Derived Through
Conventional Breeding from Sexually Compatible Plants

    This rule exempts from all FIFRA requirements, except for the
adverse effects reporting requirements at 40 CFR

[[Page 37778]]

174.71, plant-incorporated protectants that are derived through
conventional breeding from sexually compatible plants. The exempt
plant-incorporated protectants represent a subcategory of the plant-
incorporated protectants described in Option 1 in the November 23,
1994, Federal Register document (59 FR 60522). (EPA is seeking
additional comment in a supplemental document published elsewhere in
this issue of the Federal Register on whether all plant-incorporated
protectants derived from plants sexually compatible with the recipient
plant should be exempt from FIFRA requirements, regardless of how they
are introduced into the recipient plant.)
    The following language appears in 40 CFR 174.25 to describe this
subcategory:
    A plant-incorporated protectant is exempt if all of the
following conditions are met:
    (a) The genetic material that encodes the pesticidal substance
or leads to the production of the pesticidal substance is from a
plant that is sexually compatible with the recipient plant.
    (b) The genetic material has never been derived from a source
that is not sexually compatible with the recipient plant.

    The following language addressing inert ingredients in plants
derived through conventional breeding from sexually compatible plants
is added to 40 CFR 174.485, subpart X:

    An inert ingredient, and residues of the inert ingredient, are
exempt if all of the following conditions are met:
    (a) The genetic material that encodes the inert ingredient or
leads to the production of the inert ingredient is derived from a
plant sexually compatible with the recipient food plant.
    (b) The genetic material has never been derived from a source
that is not sexually compatible with the recipient food plant.
    (c) The resides of the inert ingredient are not present in food
from the plant at levels that are injurious or deleterious to human
health.

    1. Associated definitions. Pertinent definitions associated with
the exemption include:
    ``Bridging crosses between plants'' means the utilization of an
intermediate plant in a cross to produce a viable zygote between the
intermediate plant and a first plant, in order to cross the plant
resulting from that zygote with a third plant that would not otherwise
be able to produce viable zygotes from the fusion of its gametes with
those of the first plant. The result of the bridging cross is the
mixing of genetic material of the first and third plant through the
formation of an intermediate zygote.
    ``Cell fusion'' means the fusion in vitro of two or more cells or
protoplasts.
    ``Conventional breeding of plants'' means the creation of progeny
through either: The union of gametes, i.e., syngamy, brought together
through processes such as pollination, including bridging crosses
between plants and wide crosses; or vegetative reproduction. It does
not include use of any one of the following technologies: Recombinant
DNA; other techniques wherein the genetic material is extracted from an
organism and introduced into the genome of the recipient plant through,
for example, micro-injection, macro-injection, micro-encapsulation; or
cell fusion.
    ``Genome'' means the sum of the heritable genetic material in the
plant, including genetic material in the nucleus and organelles.
    ``Recombinant DNA'' means the genetic material has been manipulated
in vitro through the use of restriction endonucleases and/or other
enzymes that aid in modifying genetic material, and subsequently
introduced into the genome of the plant.
    ``Sexually compatible,'' when referring to plants, means a viable
zygote is formed only through the union of two gametes through
conventional breeding.
    ``Source'' means the donor of the genetic material that encodes a
pesticidal substance or leads to the production of a pesticidal
substance,
    ``Vegetative reproduction'' means: In seed plants, reproduction by
apomixis; and in other plants, reproduction by vegetative spores,
fragmentation, or division of the somatic body.
    ``Wide crosses'' means to facilitate the formation of viable
zygotes through the use of surgical alteration of the plant pistil, bud
pollination, mentor pollen, immunosuppressants, in vitro fertilization,
pre-pollination and post-pollination hormone treatments, manipulation
of chromosome numbers, embryo culture, or ovary and ovule cultures.
    Pertinent associated definitions in 40 CFR 174.3, several of which
are discussed in Unit VII.B.8., include:
    ``Active ingredient'' means a pesticidal substance that is intended
to be produced and used in a living plant, or in the produce thereof,
and the genetic material necessary for the production of such a
pesticidal substance.
    ``Genetic material necessary for the production'' means both:
Genetic material that encodes a substance or leads to the production of
a substance, and regulatory regions. It does not include noncoding,
nonexpressed nucleotide sequences.
    ``Inert ingredient'' means any substance, such as a selectable
marker, other than the active ingredient, where the substance is used
to confirm or ensure the presence of the active ingredient, and
includes the genetic material necessary for the production of the
substance, provided the genetic material is intentionally introduced
into a living plant in addition to the active ingredient.
    ``Living plant'' means a plant, plant organ, or plant part that is
alive, viable or dormant. Examples of plant parts include, but are not
limited to, seeds, fruits, leaves, roots, stems, flowers and pollen.
    ``Noncoding, nonexpressed nucleotide sequences'' means the
sequences are not transcribed and are not involved in gene expression.
Examples of noncoding, nonexpressed nucleotide sequences include, but
are not limited to, linkers, adaptors, homopolymers, and sequences of
restriction recognition sites.
    ``Pesticidal substance'' means a substance that is intended to be
produced and used in a living plant, or in the produce thereof, for a
pesticidal purpose during any part of a plant's life cycle (e.g., in
the embryo, seed, seedling, mature plant).
    ``Plant-incorporated protectant'' means a pesticidal substance that
is intended to be produced and used in a living plant, or in the
produce thereof, and the genetic material necessary for the production
of such a pesticidal substance. It also contains any inert ingredient
contained in the plant, or produce thereof.
    ``Produce thereof,'' when used with respect to plants containing
plant-incorporated protectants only, means a product of a living plant
containing a plant-incorporated protectant, where the pesticidal
substance is intended to serve a pesticidal purpose after the product
has been separated from the living plant. Examples of such products
include, but are not limited to, agricultural produce, grains and
lumber. Products such as raw agricultural commodities bearing pesticide
chemical residues are not ``produce thereof'' when the residues are not
intended to serve a pesticidal purpose in the produce.
    ``Recipient plant'' means the living plant in which the plant-
incorporated protectant is intended to be produced and used.
    Other definitions, relevant for plant-incorporated protectants
only, can be found at 40 CFR 174.3. 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,

[[Page 37779]]

gymnosperms such as conifers, and angiosperms such as most major crop
plants.
    2. Reporting of adverse effects for exempted plant-incorporated
protectants. This document publishes a requirement under FIFRA section
3(a) that any person who produces, for sale or distribution an
otherwise exempt plant-incorporated protectant, who obtains any
information regarding adverse effects on human health or the
environment alleged to have been caused by the plant-incorporated
protectant, must submit such information to EPA. EPA must receive the
report within 30 calendar days of receipt of such information. The
language of the requirement is set forth at 40 CFR 174.71, subpart D.

C. Establishment of 40 CFR Part 174

    This final rule establishes a new 40 CFR part 174, specifically for
plant-incorporated protectants. Subpart A sets forth definitions
specific for plant-incorporated protectants, including definitions that
are generally applicable throughout part 174. Subpart A also contains
procedures for confidential business information. Exemptions from FIFRA
are contained in subpart B. Subpart D sets forth the unreasonable
adverse effects reporting requirement at Sec. 174.71. A subpart W is
established for tolerances and exemptions from the requirement of a
tolerance published for residues of plant-incorporated protectants
under FFDCA section 408. Subpart X lists the inert ingredients that may
be used with plant-incorporated protectants that are exempt from FIFRA
and FFDCA requirements.

D. Upfront Substantiation of Confidential Business Information

    Procedures for confidential business information are set forth at
40 CFR part 174, subpart A. The rule requires that any claim of
confidentiality must accompany the information at the time the
information is submitted to EPA, and must be substantiated at the time
the claim is made.

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

    This final rule is adopted with several changes from the
1994Federal Register proposed rule. As discussed in the supplemental
document published in the April 23, 1999 Federal Register (64 FR
19958), EPA has changed the name of this type of pesticide from
``plant-pesticide'' to ``plant-incorporated protectant'' for reasons
described at Unit VII.B.2. A second significant change is due to the
1996 FQPA amendment to FIFRA. Because of this amendment, and as
discussed in supplemental documents published in the May 16, 1997,
Federal Register (62 FR 27133, 27143, 27150), ``a pesticide used in or
on food that does not meet the FFDCA section 408 safety standard also
would pose an unreasonable adverse effect under FIFRA and would not
qualify for an exemption from the requirements of FIFRA under FIFRA
section 25(b)(2).'' EPA revises the language at 40 CFR 174.21 to add
the general qualification that a plant-incorporated protectant used in
a food plant can be exempt from FIFRA requirements only if residues of
the plant-incorporated protectant in or on food or feed qualify for an
exemption from the requirement of a tolerance under FFDCA section 408.
(See Unit II. and Unit VII.D.1.iv. for additional discussion). EPA has
also determined it will adopt the definition of inert ingredient it
proposed for plant-incorporated protectants in 1994 and includes
language at 40 CFR 174.21, subpart X, to implement this decision.
    EPA in this rule finalizes only a portion of the exemptions it
proposed in 1994; specifically, the Agency exempts plant-incorporated
protectants derived through conventional breeding from plants sexually
compatible with the recipient plant. EPA has received comments that
raised significant questions on its 1994 proposed rule, and the Agency
is currently considering how to address these questions. In a
supplemental document published elsewhere in this issue of the Federal
Register EPA solicits additional public comment on the various options
it is considering to respond to the comments it has already received.
    EPA has also narrowed the adverse effects reporting requirement at
40 CFR 174.71 so that only persons who produce plant-incorporated
protectants for sale and distribution are responsible for submitting
information to EPA concerning adverse effects on human health or the
environment caused by the otherwise exempt plant-incorporated
protectant. EPA narrowed this requirement in response to comments
suggesting that the proposed language could lead to the submission of
information that was not relevant to EPA's primary concern of adverse
effects caused by the plant-incorporated protectant.
    Some modifications, primarily for clarity, or clarification, have
also been made to the language of the exemption and associated
definitions. These modifications are discussed in this document.
Discussion of these modifications can also be found in the documents
(Ref. 2) summarizing public comments and EPA response on issues
associated with plant-incorporated protectants which can be found in
the record for this rule as described in Unit VIII.

VII. Discussion of Final Rule and Public Comments

    In this unit, EPA discusses the final rule and summarizes comments
it received on the November 23, 1994, Federal Register documents. EPA
reviewed and considered all comments received on the documents
published in the November 23, 1994, Federal Register and prepared
detailed responses to these comments. These can be found at appropriate
points in this preamble, and in the Agency's summary of public comments
and EPA's response on issues associated with plant-incorporated
protectants (Ref. 2), which is located in the official record for the
rule as described in Unit VIII.

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 addressed to all five dockets.
    On July 22, 1996, EPA published in the Federal Register (61 FR
37891) a supplemental document seeking additional comment on how it
should view the concept of inert ingredient with regard to plant-
incorporated protectants. EPA received comments in response to that
supplemental document. On May 16, 1997, EPA published in the Federal
Register (62 FR 27132, 27142, 27149) supplemental documents to provide
the public an opportunity to comment on EPA's analysis of how certain
amendments to FFDCA and FIFRA by the FQPA apply to EPA's proposed
exemptions under FIFRA for plant-incorporated protectants derived from
closely related plants, and proposed exemptions under FFDCA for
residues of these plant-incorporated protectants and received comment.
On April 23, 1999, EPA published in the Federal Register (61 FR 19958)
a supplemental document on whether to rename this type of pesticide.
EPA received comments on that supplemental document. Copies of all
comments received are available in the official record for the rule as
described in Unit VIII.

[[Page 37780]]

    EPA also received comments after the comment period for the rule
had closed. Eleven scientific societies sent a report entitled
``Appropriate oversight of plants with inherited traits for resistance
to pests'' (Ref. 3). The National Academy of Sciences produced a report
entitled ``Genetically modified pest-protected plants: Science and
regulation'' (Ref. 4). These comments did not raise issues beyond those
that had been raised by comments submitted during the comment period
for the rule. Therefore, EPA has not included these comments as part of
this rulemaking, and will not respond to them in this action.

B. What Are the Major Comments on EPA's Approach?

    More comments supported EPA's approach than opposed it. Comments on
EPA's approach to plant-incorporated protectants can be categorized as
follows. In general, those comments supporting EPA's approach agree
that FIFRA gives EPA the authority to regulate substances that plants
produce for protection against pests if humans intend to use these
substances for preventing, destroying, repelling or mitigating any
pest. Second, the commenters believe an approach that regulates the
substance while exempting the plant from regulation is appropriate.
Some comments, while in general supporting the approach, had
reservations about the definition of plant-incorporated protectant, and
definitions directly associated with the definition of plant-
incorporated protectant. Others, while recognizing EPA's authority
under FIFRA, thought an approach to regulation based on whether genetic
engineering, e.g., recombinant DNA (rDNA), was used to introduce
genetic material for pesticidal purposes into plants, better addressed
risk and public concerns. These commenters urged EPA to implement such
an approach.
    Those comments opposing EPA's approach can in general be described
as: First, those opposed to designating plant defense substances as
pesticides, including those that believe that FIFRA should only apply
to chemical pesticides; second, those who urged a more narrow
definition of plant-incorporated protectant; third, those who believe
that use of non-governmental peer review and standards of practice
accepted in the plant breeding industry are adequate and EPA oversight
is unnecessary; and fourth, those who believe that EPA's approach
discriminates against rDNA technology and that any discrimination
against rDNA technology is unscientific. There also appears to be some
confusion evidenced in comments concerning the concept of ``intent'' in
the FIFRA section 2 definition of pesticide. Some comments expressed
concern that the term, ``pesticide,'' has a negative connotation with
the public. Some of these commenters requested that, at a minimum,
plant defense substances not be given the name ``plant-pesticide.''
    1. How can plant defense substances be pesticides? EPA received
seven comments that expressed concern with the designation of defense
substances produced by plants as pesticides. Most of these comments
stated that it was inappropriate to consider plant defense substances
to be pesticides and questioned the Agency's determination that plant
defense substances are pesticides.
    FIFRA section 2(u) defines ``pesticide'' to include any substance
or mixture of substances intended for preventing, destroying,
repelling, or mitigating any pest. Plant defense substances are clearly
pesticides under the FIFRA section 2 definition of pesticide when
humans intend to use them ``for preventing, destroying, repelling, or
mitigating any pest'' regardless of how the pesticidal capabilities
were introduced into the plant (e.g., whether by traditional breeding
or through the techniques of modern biotechnology). The suggestion that
substances, or mixtures of substances, in plants that humans
intentionally use for preventing, destroying, repelling, or mitigating
a pest, should not be considered pesticides is not tenable. If the
substances were isolated from the plant and sold as pesticides, no one
would argue that they were pesticides. Clearly, substances in plants
that humans intend to use for preventing, destroying, repelling or
mitigating a pest meet the FIFRA section 2 definition of pesticide and
Congress has specifically made EPA responsible for regulating
pesticides under FIFRA and FFDCA section 408.
    2. Why is EPA giving these pesticides a different name? EPA
recognizes the unique use pattern of these pesticides, which are
produced and used in the living plant. Thus, in the November 23, 1994,
Federal Register (59 FR 60496), EPA suggested giving these types of
pesticides a unique name, ``plant-pesticides,'' in order to distinguish
them from chemical, microbial, or biochemical pesticides. EPA believes
a unique name for this type of pesticides benefits the public by
providing the means to more readily identify regulations specific to
this type of pesticide in the CFR.
    In response to the request that EPA consider another name, the
Agency published in the April 23, 1999, issue of the Federal Register
(64 FR 19958) a document requesting comment on the advisability of
substituting an alternative name for the term ``plant-pesticide,'' and
requesting appropriate alternative names for this type of pesticide.
EPA also specifically requested comment on whether the alternative
name, ``plant-expressed protectants,'' would be an acceptable name for
this type of pesticide. EPA noted that if the Agency changed the name
of such pesticides, the change would only affect the name. It would not
affect the status of the pesticidal substance or the genetic material
necessary to produce it. Even with a different name, these would still
be pesticides under FIFRA section 2(u). Similarly, a change of name
would not affect any regulatory requirements.
    In response to the April 23, 1999, Federal Register supplemental
document, EPA received 60 comments. Of these 60 comments, eight
comments supported the name ``plant-expressed protectants.'' These
commenters argued that the term ``plant-pesticide'' is inappropriate
and inaccurate because in standard English it means ``pest killer,''
and many of the pest-resistance mechanisms enhanced by genetic
modification do not kill pests in any way, but rather make the crop
plants undesirable to pests or not vulnerable to pest attack. These
commenters also argued that if plants are labeled as pesticides, a
negative connotation could attach to plants. Such plants might be
poorly received by the public, and the public perception of a promising
branch of science could be tarnished. These commenters also expressed
concern that such negative perceptions might lead to labeling
requirements or nontariff trade barriers.
    Seven comments offered other alternative names without comment on
the merit of changing the name. Examples of such names include:
Endocides, endogenous bio-control (ebc, or endobio, or endob), enhanced
plant protectant, plant protection agent, plant defense agent,
plantocides, plendocides, pliocides, intrinsic plant biocontrol agent,
intrinsic floral protectant, expressogen, floral defense agent (fda),
floral protectant, and gene-transferred protectants.
    Eight comments opposed a change of name. These comments, for the
most part, thought the name ``plant-pesticide'' appropriate. Some of
these commenters argued that the term ``plant-pesticide'' succinctly
explains the meaning of the term, i.e., pesticidal

[[Page 37781]]

substances introduced into plants. Others arguing for retention of the
name ``plant-pesticide'' stated that the term ``pesticide'' does not
necessarily have a negative connotation. Several of these commenters
asked why the Agency would propose to fix something that is not broken.
Several commenters arguing against a change of name stated that EPA
should be transparent in its actions, and a pesticide should be called
a pesticide. One commenter argued that the term ``plant-pesticide'' has
been used by EPA since the early 1990s. It has become a term of art and
it would be confusing to change the name. Other commenters stated that
if EPA changes the name ``plant-pesticide'' to a more euphemistic name
to satisfy one interest group, other interest groups will soon be
urging it to change the names of other types of pesticide products to
have better marketing potential. These commenters argued against
setting such a precedent. Others feared that it would make EPA's effort
to control unregistered pesticides more difficult.
    Four comments offered alternative names such as Franken-plants,
Frankenstein pesticides, Pandora pesticides, products-of-sexual-abuse,
alien pesticides, or foreign pesticides.
    Among the commenters opposed to a renaming, some also specifically
opposed the term ``plant-expressed protectants''. Those opposed to the
name ``plant-expressed protectants'' stated that the name obscures the
legal issues and attempts to mislead the public into believing that
these pesticides are not pesticides at all.
    After reviewing all comments, EPA decided to change the name of
this category of pesticides from ``plant-pesticides'' to ``plant-
incorporated protectants.'' From comments EPA has received both in the
comment period on the 1999 supplemental document discussing the
possibility of changing the name, and over the years since the 1994
proposed rule was issued, the Agency concludes that many people are not
aware of, or do not understand, the FIFRA definition of pesticide. For
example, some comments argued that the term ``plant-pesticide'' is
inappropriate and inaccurate because it means ``pest killer'' and many
pest-resistance mechanisms do not kill pests but rather make the plant
undesirable or not vulnerable to pest attack. EPA notes that the term
``pesticide'' in FIFRA section 2 means, in part, ``any substance or
mixture of substances intended for preventing, destroying, repelling,
or mitigating any pest.'' A pest-resistance mechanism that makes the
plant undesirable or not vulnerable to pest attack falls within the
definition of pesticide because such mechanisms ``prevent'' or
``repel'' a pest. EPA recognizes that the term ``protectant'' may
better describe for the general public pesticides in plants that
function by preventing, repelling or mitigating a pest because the term
encompasses these concepts, in addition to the concept of destroying a
pest. A number of suggested names received in response to the April 23,
1999, Federal Register, document utilized the word ``protectant.''
    In addition, the name ``plant-pesticide'' appears in some instances
to have led some people to believe the Agency is regulating plants,
despite the Agency's numerous statements that EPA would not regulate
the plant per se, but rather substances within the plant when these
were used for pesticidal purposes. EPA recognizes that the name
``plant-pesticide'' may have contributed to this confusion, as some
people may interpret the term ``plant-pesticide'' to mean a ``plant
that acts like a pesticide.'' EPA believes the adjective ``plant-
incorporated'' more accurately conveys the sense that these pesticides
are produced and used in the plant. EPA will therefore utilize this
adjective in concert with the term ``protectant'' to describe this type
of pesticide. EPA chose the adjective ``plant-incorporated'' rather
than the adjective ``plant-expressed,'' because the word ``expressed''
represents a technical term of art, and in this instance it appeared
preferable to use the term ``incorporated'' which also encompasses a
meaning found in the common English dictionary (Ref . 5), i.e.,
``joined or combined into a single unit or whole''. The term ``plant-
incorporated'' may thus be better understood by the general public than
the term ``plant-expressed.''
    EPA discounted names received in comments that focus inaccurately
on pesticides introduced into plants through genetic modification,
e.g., gene-transferred protectants. Names focusing on those pesticides
introduced into the plant through the techniques of genetic engineering
are too limited, in that such names do not describe the full range of
this type of pesticide. This rule addresses pesticides that can be
present in a plant because they evolved in the plant, were moved
between plants through mating, or were introduced into plants through
the techniques of modern biotechnology (e.g., rDNA).
    With regard to the concern that other interest groups will soon
urge the Agency to change the names of other types of pesticide
products to have better marketing potential, EPA recognizes that this
may indeed be the case. Indeed, one commenter on the April 23, 1999
Federal Register document supplied lengthy comments supporting a name
change, and indicating that in the future his organization will suggest
that EPA initiate a rulemaking to adopt other terms to describe other
products which are regulated under FIFRA. EPA will evaluate each such
request on its own merits.
    It is not clear to EPA how changing the name of this type of
pesticide would affect the Agency's ability to control unregistered
pesticides. The comment did not provide a description of how this might
occur. As previously stated, the name of the product does not affect
the manner in which it is sold or intended to be used, which determines
whether a product falls within EPA's jurisdiction under FIFRA.
    3. Does FIFRA apply to pesticides other than traditional
pesticides? EPA does not agree with the contention that FIFRA was meant
to regulate only chemical pesticides, such as those extracted from
plants or synthesized by petroleum chemistry. The definition of
pesticide in FIFRA section 2(u) is not, and has never been, limited to
chemical pesticides. Indeed, FIFRA section 2(u) specifically states
that a pesticide is any substance or mixture of substances intended for
preventing, destroying, repelling, or mitigating any pest, or intended
for use as a plant regulator, defoliant or desiccant or a nitrogen
stabilizer. Pesticides other than chemical pesticides have been, and
continue to be, registered under FIFRA. The first microbial pesticide
was registered in 1948 and other biological substances, e.g.,
pheromones, have been regulated by EPA as pesticides since 1979.
Moreover, in 1975, the Committee on Agriculture of the House of
Representatives during the debate on the bill (House Report 8841) to
extend FIFRA, as amended, for one year, specifically rejected a
proposed amendment that would have excluded from the definition of
pesticide ``biological parasites, living organisms and predators of
pests'' other than microorganisms such as bacteria, fungi or viruses
(Ref. 6). Congress again acknowledged in 1996 that the term
``pesticide'' is not limited to chemicals when it enacted FIFRA section
3(c)(10)(B) and established expedited review for both ``biological and
conventional pesticides'' (7 U.S.C. 136a(c)(10)(B)). Plant-incorporated
protectants, microbial pesticides, biochemicals and semiochemicals
(e.g., pheromones) are included under the rubric of biological
pesticides.
    EPA also does not agree with the implication that risks associated
with

[[Page 37782]]

pesticide use stem only from the use of chemical pesticides. While EPA
believes that as a pesticide class, biological pesticides are more
likely to present lower levels of risk, there are certainly chemical
pesticides that also fall into the category of ''safer pesticides.''
There may also be biological pesticides, including some plant-
incorporated protectants, that could present higher levels of risk.
    4. Why has EPA not implemented a narrower definition of plant-
incorporated protectant? Some comments urged EPA to adopt a more narrow
definition of plant-incorporated protectant. These comments include
those who urged EPA to define plant-incorporated protectants to be only
those pesticidal substances that are introduced into plants from
sources outside the plant kingdom, and those who urged the Agency to
utilize toxicity to define a plant-incorporated protectant.
    FIFRA section 2 defines pesticide broadly as any substance or
mixture of substances intended for preventing, destroying, repelling,
or mitigating any pest, or intended for use as a plant regulator,
defoliant, or desiccant or a nitrogen stabilizer (7 U.S.C. 136 (u)).
The FIFRA section 2 definition of pesticide does not make any reference
to conditions such as origin nor the level or kind of toxicity that a
product must exhibit in order to be considered a pesticide. Instead of
defining a substance either in or out of FIFRA based on its toxicity or
origin, FIFRA section 25(b) authorizes EPA to exempt pesticides from
FIFRA requirements. In the actions it takes today, EPA exempts plant-
incorporated protectants derived through conventional breeding from
sexually compatible plants. These actions significantly reduce the
number of plant-incorporated protectants subject to FIFRA requirements,
although they have no effect on the FIFRA section 2 definition of
pesticide.
    5. How do substances produced and used in living plants meet the
intent standard in the FIFRA definition of pesticide? EPA received
comments indicating some confusion may exist in the broader community
regarding the concept of ``intent'' in the FIFRA section 2(u)
definition of pesticide, and in how this concept applies to plant-
incorporated protectants. One comment, for example, argued that plant
defense substances should not be pesticides and stated that by ``strict
interpretation of the FIFRA definition of pesticide, substances
produced by plants that provide protection against pests and disease
cannot be considered pesticides because plants do not `intend' nor
`produce to protect themselves.''' The commenter went on to state that
``this argument would certainly be correct for wild plants because only
natural selection has been involved in stabilization of the character.
This argument would also hold for many cases of cultivars improved
through breeding programs because many times breeders select for the
best yielding plants without specific regard to specific disease or
pest; thus there is no intent.''
    A key statutory element in the FIFRA definition of pesticide is
whether a human ``intends'' that a substance or mixture of substances
be used for destroying, preventing, repelling, or mitigating a pest.
Just as EPA does not evaluate whether a granule of a traditional
chemical pesticide ``intends'' to function as a pesticide in
determining whether a substance is a pesticide, the Agency did not base
its determination that plant-incorporated protectants are pesticides on
the belief that a plant ``intends'' to prevent, destroy, repel, or
mitigate a pest. Rather, EPA considers the actions of the humans
selling, distributing, or using the substance. To the extent a human
relies on a plant's existing pest control properties, the human
demonstrates pesticidal intent; if he or she uses, or sells a plant
knowing that it typically produces a pesticidal substance he or she
``intends'' for it to be produced. For example, EPA considers that a
clear human intent is present when a seller or distributor claims,
states, or implies (by labeling or advertising or otherwise) that a
substance or organism, either by itself or in combination with other
substances or organisms, can or should be used as a pesticide. An
example of this would be a company advertising that the cotton seed it
is selling would produce cotton plants expressing an insecticidal
protein effective against lepidopteran pests. Another example of intent
would be a company advertising that a certain variety of squash resists
fungal disease.
    Yet a third example of a situation where a human displays a
pesticidal intent involves a person who sells or distributes a product
with actual or constructive knowledge that the product will be used, or
is intended to be used, for a pesticidal purpose (see 40 CFR 152.15).
EPA considers that the person introducing genetic material encoding a
pesticidal substance into a plant displays such an intent. For example,
the Bt delta-endotoxin is a well-known insecticidal protein with no
other known function; introduction of such a protein into a plant
displays a clear pesticidal intent.
    Another example of such intent is the use of a name for the product
which includes the name of a substance commonly recognized as having
pesticidal properties. Such a product will be recognized as a pesticide
because the targeted consumer would recognize from the product name
that the product contains a pesticide.
    A substance in a plant evolving in the wild in response to natural
selection is not subject to FIFRA until a human intends the substance
to be sold, distributed in commerce, or used to prevent, destroy,
repel, or mitigate a pest. Similarly, a cultivar selected, sold and
distributed with reference only to yield considerations, without
exhibiting any indicia of intent for the cultivar to be used as a
pesticide, does not contain substance(s) meeting the FIFRA section 2(u)
definition of pesticide. EPA would not treat such a cultivar, or a
substance within it, as a pesticide until a human exhibits the
requisite intent that the substance(s) or cultivar be used for
preventing, destroying, repelling or mitigating a pest.
    6. Why does EPA have a role to play, in light of peer review and
existing standards of practice in the plant breeding industry? Some
commenters opposed to EPA's approach argued that use of non-
governmental peer review and standards of practice accepted in plant
breeding are adequate. As discussed in Unit VII.A.5., whether a
substance is a pesticide under the FIFRA section 2 definition depends
on the intent of those selling or distributing it. Once something falls
within the FIFRA definition of a pesticide, it must generally be
registered before it can be sold or distributed in the United States,
unless EPA can make the requisite findings to exempt it. For some
plant-incorporated protectants, EPA believes that there are
circumstances where it is necessary that the Agency employ its
statutory authorities to ensure use will not cause unreasonable adverse
effects on the environment, and/or ensure that residues of the plant-
incorporated protectant can be safely consumed. Some plant-incorporated
protectants may be isolated from novel sources (e.g., scorpions, frogs,
microorganisms), and may present novel, unknown and/or unfamiliar,
toxicological profiles. For example, most of the plant-incorporated
protectants reviewed to date by EPA have been insecticidal proteins
isolated from microbial sources. These insecticidal proteins are
regulated by EPA when they are formulated to be sprayed/dusted on
plants. Many of the risk considerations associated with use of the
insecticidal proteins in the sprayed/dusted product are present

[[Page 37783]]

when the proteins are formulated as a plant-incorporated protectant,
even though the route of exposure may be different for the different
formulations.
    There are also substances that occur naturally in plants, including
major crop plants, that can cause toxic effects when present at high
concentrations or when presented in novel exposures (Refs. 7 and 8). As
these substances could be used as plant-incorporated protectants, EPA
believes it is important for the Agency to be able to employ its
statutory authorities to ensure use will not cause unreasonable adverse
effects on the environment.
    EPA, nonetheless, recognizes that plant breeding in the United
States has a good record of providing a safe food supply and that plant
breeders employ accepted standards of practice to maintain this record.
This good record provides support to the Agency's determination that it
can exempt plant-incorporated protectants derived through conventional
breeding from sexually compatible plants from almost all regulatory
oversight, relying only on the post-market reporting of adverse
effects. EPA believes that the clarification in this rule that the
Agency will not regulate plants per se, in conjunction with the
exemption it is issuing today, limits EPA's regulatory role in
conventional plant breeding and ensures that the Agency does not
unnecessarily supplant the self-regulating aspects of plant breeding.
    Some comments that in general otherwise supported EPA's approach,
encouraged EPA to ensure that pest resistant crops derived by
conventional plant breeding are not subjected to unnecessary
regulation. As explained above, EPA believes that its clarification
that it would not regulate plants per se, and the exemption it is
issuing today, limit EPA's regulatory role in conventional plant
breeding and ensures that the Agency does not subject pest-resistant
crops derived by conventional breeding to unnecessary regulation.
    7. What were the comments on regulatory procedures? One comment
recommended that, before EPA's regulations are finalized, EPA address
issues such as labeling, and field testing and seed production. Another
comment recommended that the Agency develop guidelines, in conjunction
with the scientific community and industry, to help those who are
developing products from these new technologies to determine the
factors and situations that might merit regulation by the EPA.
    Subsequent to publication of the 1994 Federal Register documents,
EPA under existing regulations in 40 CFR parts 152 through 173 and 40
CFR parts 177 through 180, took several actions with regard to plant-
incorporated protectants. EPA issued, for example, a number of EUPs for
field testing of plant-incorporated protectants, exemptions from the
requirement of a tolerance for residues of plant-incorporated
protectants, and registrations for plant-incorporated protectants.
    Together, these actions show how EPA to date has approached
labeling, field testing, large scale planting for seed increase, and
data needs for evaluating plant-incorporated protectants. In the
future, EPA anticipates proposing additional regulations for plant-
incorporated protectants that would tailor existing regulations for
pesticides so that the procedures would better fit the characteristics
of plant-incorporated protectants. Until such regulations can be
issued, EPA will continue to apply the regulations in 40 CFR parts 152
through 173 and 40 CFR parts 177 through 180 to plant-incorporated
protectants, unless superceded by the regulations published in 40 CFR
part 174.
    i. How has EPA approached labeling? One commenter asked whether
labels are expected to appear on bags of seed, and, if so, what
information should be on the label. Labeling is generally required by
FIFRA for pesticides. Labeling includes both written material
accompanying the pesticides and labels on or attached to the pesticide,
its container, or wrapper (7 U.S.C. 136 (p)). In its 1994 policy
statement for plant-incorporated protectants, EPA attempted to provide
the broad outlines of how it would approach labeling. The Agency
recognized in the 1994 Federal Register policy statement (59 FR 60510)
that certain types of labeling which are appropriate for chemical
pesticides will not be practical for plant-incorporated protectants. In
issuing registrations for plant-incorporated protectants, EPA has
followed the labeling regulations at 40 CFR part 156. Under current
procedures for plant-incorporated protectants, the pesticide label is
held by the producer or the producer's agent(s) and is attached to seed
sent to seed propagators. The actual pesticide label requires that
informational material must be provided to the farmer with bags of seed
sold to farmers. The informational material should indicate that the
seed contains a registered plant-incorporated protectant, and its
primary purpose is to prevent needless spraying of chemical pesticides.
The informational material also conveys any other information pertinent
to the grower on the registration and use of the plant-incorporated
protectant. Recognizing that the regulations at 40 CFR part 156 were
written for chemical pesticides, EPA intends in the future to propose
at 40 CFR part 174, labeling requirements specifically tailored for
plant-incorporated protectants. No label of any type is required for
the plant-incorporated protectants exempted in new 40 CFR part 174.
    ii. How has EPA approached seed increase? One commenter noted that
to produce seed for sale, companies will need to plant significant
acreage to generate commercial quantities of seed. The commenter asked
how such developmental work will be carried out, as such work does not
fall under the traditional usage of an Experimental Use Permit (EUP),
because an EUP is granted for generation of data to support
registration. Since 1994, EPA issued three ``seed increase''
registrations. Seed increase registrations were issued to allow
producers to grow seed for commercial sale, and were limited to seed
increase activities. Most registrants, however, currently obtain a
registration prior to beginning seed increase activities sufficiently
large to produce seed for commercial sale and distribution.
    iii. What is EPA doing in terms of guidance? With regard to the
comment that the Agency develop guidelines to help those who are
developing products from these new technologies, EPA, in its November
23, 1994 Federal Register policy statement (59 FR 60511), attempted to
provide a general perspective on information needs for plant-
incorporated protectants. The Agency in the future intends to establish
data requirements specific to plant-incorporated protectants through a
public notice and comment process. In establishing these testing
requirements, EPA will propose the tests it believes are appropriate,
indicating the circumstances when each study would be required,
conditionally required, or not required. These proposed requirements
will be widely available for public comment and will be reviewed in a
public meeting of the FIFRA SAP. Amendments can be made to the proposed
guidelines as part of the notice and comment process. EPA has already
begun this process with the public meetings on December 8, 1999,
February 29, 2000 and June 7, 2000 of the FIFRA SAP on data
requirements for product identity, human health and non-target organism
effects of proteineous plant-incorporated protectants.
    8. What comments were received on the definitions? Some commenters
who supported EPA's approach thought the

[[Page 37784]]

plant-incorporated protectant definitions and other associated
definitions appropriate. Other comments, while in general supporting
the approach, expressed reservations about the definitions. These
comments focused primarily on three issues: First, whether the
``genetic material necessary for the production'' should be part of the
plant-incorporated protectant definitions; second, clarification of how
this term is to be interpreted in several specific circumstances, e.g.,
with regard to multiple copies of a gene; and, third, what the term
``living'' was intended to signify in the definitions, particularly
with regard to regulation of plant-incorporated protectants intended
for post-harvest pest control.
    i. Why is EPA including genetic material in the plant-incorporated
protectant definitions? EPA received several comments on including
``genetic material necessary for the production'' in the plant-
incorporated protectant definitions. Some comments supported inclusion.
Other commenters opposed including genetic material in the definitions
for various reasons: First, that inclusion of genetic material in the
definition runs counter to the traditional definition of pesticide.
Second, commenters disagreed with the presumption that the presence in
a plant of genetic material necessary for producing a pesticidal
substance indicates a pesticidal intent since the genetic material will
still be in the plant when there is no longer any ``pesticidal
intent,'' e.g., once a crop has been harvested and regenerative
material no longer used for future plantings. Third, commenters argued
that including the genetic material necessary for the production in the
plant-incorporated protectant definitions is not necessary for EPA to
be able to request data on the genetic material. Fourth, commenters
asserted that including genetic material in the definitions results in
EPA effectively regulating the whole plant because genetic material is
found in all parts of the plant. Fifth, commenters alleged that
inclusion of the genetic material in the definitions makes EPA's
approach inconsistent with policies of the Food and Drug Administration
(FDA). Sixth, the comments raised arguments that inclusion of genetic
material in the definitions would add an unnecessary layer of
complexity to the regulatory process. One commenter suggested that EPA
should, on the basis of the above listed considerations, reevaluate
EPA's inclusion of the genetic material in the plant-incorporated
protectant definitions. The comment suggested that if the Agency
concludes that ``genetic material'' must remain in the plant-
incorporated protectant definitions, it should be an inert ingredient,
not part of the definition of active ingredient.
    Based on several considerations, EPA has determined that the
``genetic material necessary for the production'' will continue to be
part of the plant-incorporated protectant definitions. First, the
conclusion that such genetic material is part of a plant-incorporated
protectant is consistent with FIFRA which defines ``pesticide''
broadly, and encompasses both single substances and mixtures of
substances intended for preventing, destroying, repelling or mitigating
a pest. The genetic material and the substance it encodes for are such
a mixture. In this instance, the genetic material is introduced into
the plant with the intent to cause a pesticidal effect; i.e., with the
intent that the substance(s) produced from this genetic template will
ultimately result in a pesticidal effect. Thus, the genetic material,
as well as the pesticidal substance, are introduced with the intention
of obtaining a pesticidal benefit. Both the genetic material and the
pesticidal substance meet the FIFRA statutory definition of pesticide.
Second, including the genetic material in the definitions permits EPA
to address plant-incorporated protectants during stages of the plant's
life cycle or in plant parts (e.g., in pollen or seed) where the
pesticidal substance itself is not produced or is produced in amounts
below the limits of detection. EPA believes that including the genetic
material in the definitions maintains regulatory continuity during such
periods in a plant's life cycle and has concluded that this regulatory
continuity is important for comprehensively addressing potential risks
associated with plant-incorporated protectants within a cohesive and
rational regulatory policy. Third, inclusion of the genetic material in
the definitions allows the Agency to more readily verify the presence
of the plant-incorporated protectant in the plant or plant material
because, in many instances, it may be more difficult technically to
assay for the substance than it is to assay for the genetic material.
Fourth, inclusion of genetic material in the definitions allows EPA to
address the spread of the pesticidal substance in the environment
through the spread of the genetic material necessary for the production
of the pesticidal substance.
    a. Why is inclusion of genetic material in the definition
consistent with the traditional use of the term pesticide? Many of the
commenters that disagreed with the inclusion of genetic material in the
plant-incorporated protectant definitions argued that including the
genetic material runs counter to the traditional use of the term,
``pesticide.''
    EPA finds that inclusion of the genetic material in the plant-
incorporated protectant definitions is consistent with FIFRA. FIFRA
section 2(u) defines the term ``pesticide'' broadly to include ``any
substance or mixture of substances intended for preventing, destroying,
repelling, or mitigating any pest'' (7 U.S.C. 136 (u)). Section 2(u)
defines a pesticide in terms of the intent of humans to exert a
deleterious effect upon pests. It does not limit pesticides to
substances that directly cause such a deleterious effect (7 U.S.C. 136
(u)). Indeed, EPA has registered chemical substances that do not
directly have pesticidal effects but which, when applied to plants, are
transformed into the substance having the actual pesticidal effect.
    Consistent with FIFRA section 2(u), EPA has concluded that the
genetic material necessary for the production of a pesticidal
substance, intentionally introduced into a plant, meets the FIFRA
statutory definition of a pesticide. Such material is introduced into a
plant with the intent of ultimately producing a pesticidal effect even
though the genetic material may not itself directly affect pests. The
commenter did not identify any specific instances of past Agency usage
that would conflict with this conclusion, and EPA is not aware of any.
    b. Why is the genetic material part of the active ingredient
definition? EPA does not agree with the comment suggesting that the
genetic material be considered an inert ingredient and not part of the
active ingredient. In deciding to include the genetic material
necessary for the production of a pesticidal substance in the
definition of active ingredient, the Agency considered the statutory
definitions of inert and active ingredients. Based on these
definitions, EPA concluded that the genetic material necessary for the
production of a pesticide fit more closely within the section 2(a)
definition of ``active ingredient.'' Section 2(a) defines an active
ingredient as, among other things ``the ingredient which will prevent,
destroy, repel, or mitigate any pest'' (7 U.S.C. 136(a)(1)). The
genetic material is a necessary component of the ability of the plant-
incorporated protectant to prevent, destroy, repel or mitigate a pest,
as without the genetic material the plant cannot produce the pesticidal
substance (See also, 7 U.S.C. section 136(a)(2)). Moreover, the genetic
material was inserted with the intention

[[Page 37785]]

of obtaining a pesticidal effect: the expression of a substance that
will prevent, destroy, repel, mitigate any pest. Consequently, EPA will
not define the genetic material necessary for the production of a
pesticidal substance as an inert ingredient, as suggested by comment.
    c. How does including genetic material in the definitions relate to
EPA's ability to request data? EPA received comment stating that the
Agency has the authority to require all relevant data for a plant-
incorporated protectant, including data related to the genetic
material, regardless of whether the genetic material is part of the
definitions. The same comment noted that deleting the phrase ``genetic
material necessary for the production'' from the definitions will not
prevent EPA from addressing salient issues related to the spread of
genetic material in the environment, or to the levels of the pesticidal
substance present in the plant.
    EPA agrees that it has broad authority under FIFRA to gather and
review data/information on any aspect of a pesticide product or its use
in the environment, including data on fate in the environment. However,
if a particular aspect of a plant-incorporated protectant is not part
of the active or inert ingredient definition for plant-incorporated
protectants, it is part of the plant and this rule clarifies that the
plant is exempt under FIFRA section 25(b)(1) from FIFRA requirements
(40 CFR 152.20). Thus, data gathering considerations are not the
primary reason the Agency is including the genetic material in the
definitions.
    The comment also stated, with regard to EPA's argument that
including the genetic material in the definitions permits the Agency to
address plant-incorporated protectants during stages of the plant's
life cycle where the pesticidal substance itself is not produced, that
EPA has the authority to address pesticides at various stages of the
product's life cycle, in soil, water and food without including the
genetic material in the definitions. EPA agrees that it has the
authority to control pesticide residues and the metabolites and
degradates of pesticides in the environment and in food. However, as
previously noted, unless the genetic material is part of the plant-
incorporated protectant, it will be exempt under 40 CFR 152.20. The
Agency also believes that in certain circumstances for technical
reasons it is easier to identify the presence of the genetic material
than the pesticidal substance, and considered this in deciding whether
to include the genetic material in the definitions.
    d. Is inclusion of the genetic material in the definitions a
disincentive to developers? The comment provided no specific reason why
inclusion of genetic material in the definitions would hinder product
development or increase costs. EPA has registered eleven plant-
incorporated protectants to date, and including the genetic material in
the definitions does not appear to have discouraged companies from
developing plant-incorporated protectants.
    e. Is inclusion of the genetic material in the definitions
consistent with the assumption of ``intent''? One commenter opposed
EPA's proposal to include the genetic material necessary for production
of the pesticidal substance in the definitions of active ingredient and
plant-incorporated protectant on the grounds that it is inconsistent
with EPA's longstanding implementation of FIFRA, as well as the
statute. Specifically, the commenter disagreed with EPA's statement
that the genetic material ``is introduced into the plant with the
intent that it will ultimately result in a pesticidal effect,''
alleging that this equates the presence of genetic material with
pesticidal intent, and fails to acknowledge that a substance can have
both pesticidal and non-pesticidal uses, depending on how the substance
is intended to be used. The commenter contended that ``once the crop
has been harvested and regenerative material removed for future
plantings, any genetic material that remains in the food, feed, or
other product no longer is accompanied by any `pesticidal intent.'''
    EPA disagrees that its decision to include the genetic material in
its definitions of a plant-incorporated protectant and active
ingredient fails to adequately recognize the role ``intent'' plays
under FIFRA, or that its decision necessarily equates the presence of
genetic material with pesticidal intent. The commenter appears to have
misunderstood EPA's statements on this issue, and their implications
with respect to EPA's regulation of such substances under FIFRA.
    As a preliminary matter, EPA believes that including the genetic
material necessary to produce a pesticidal substance in the plant-
incorporated protectant definitions is consistent with key statutory
definitions, as explained at length in Unit VII.B.8.i. FIFRA section
2(u), defines pesticide to include ``any substance or mixture of
substances intended for preventing, destroying, repelling, or
mitigating any pest'' (7 U.S.C. 136(u)). Under FIFRA, a substance is a
pesticide if it is intended to be used for a pesticidal purpose. And as
EPA has previously explained, substances that are sold or distributed
with the intent that they ``prevent, destroy, repel, or mitigate any
pest'' fall within the FIFRA section 2(u) definition of a pesticide. In
the absence of other facts indicating a contrary intent, EPA believes
that it is reasonable to presume that the introduction into a plant of
genetic material that produces, or is intended to produce, a pesticidal
substance is clear evidence of a pesticidal purpose. EPA's
interpretation is based on the fact that without the genetic material,
the pesticidal substance, the substance that will actually ``prevent,
destroy, repel, or mitigate any pest,'' cannot be produced by the
plant. The sole reason the genetic material is inserted into the plant
is to ensure that the pesticidal substance is produced. This is fully
consistent with EPA's approach to traditional chemical pesticides (see,
40 CFR 152.15(b)).
    However, regulation of the genetic material necessary for the
production of a pesticidal substance as an active ingredient or a
plant-incorporated protectant in one plant does not mean that some
portion of the genetic material cannot be used for another purpose
without being subject to FIFRA. At no time has EPA stated that, for
example, once a particular promoter is used as part of the construct
inserted to produce a pesticidal substance in a plant, thereafter,
irrespective of the rest of the genetic construct that is inserted, EPA
will always consider insertion of the promoter to demonstrate
pesticidal intent. Rather, EPA's statement was intended to clarify
that, in the absence of indicia indicating a contrary intent, because
the purpose of the introduced genetic material is to produce a
pesticidal substance, the insertion of the genetic material will be
taken as evidence of a pesticidal intent, and the resulting product
will be considered a pesticide under FIFRA. In Unit VII.B.5., EPA
discusses in some detail, examples of actions that the Agency
interprets as indicia of a pesticidal intent. Clarity on this point is
of particular concern with respect to these products because the plant
in which the plant-incorporated protectant is contained will remain
exempt, and anything that is not part of the plant-incorporated
protectant will therefore not be regulated by the Agency under FIFRA.
    Thus, EPA agrees with the commenter that under some circumstances
the pesticidal intent would cease after harvest, and under such
circumstances, the sale of the produce as food or feed would be subject
to the FFDCA, rather than FIFRA. The mere presence of such genetic
material in the produce will not

[[Page 37786]]

cause EPA to treat the produce as a pesticide, absent any indicia of
intent to sell, distribute in commerce, or use the produce itself as a
pesticide, any more than the presence of traditional pesticide chemical
residues renders a food bearing those residues a pesticide. However, if
the produce is intended to be used, sold or distributed as containing a
plant-incorporated protectant, EPA will regulate it as such. To clarify
this, EPA has revised the definition of plant-incorporated protectant,
and included a definition of the term ``produce thereof,'' to
specifically exclude the products of a plant-incorporated protectant
merely bearing ``pesticide chemical residues,'' such as the genetic
material, from the definition of a plant incorporated protectant, when
the plant-incorporated protectant in the produce is not intended to
provide post-harvest control. EPA provides further discussion of its
treatment of products that are intended to provide post-harvest control
in Unit VII.B.8.iii., and the associated response to comments document
(Ref. 2).
    The question of pesticidal intent arises in making the
determination that the substance being sold or distributed in commerce
is a pesticide that must be registered under FIFRA, or whose use is
subject to regulation under section 3(a), and for which a tolerance
must be granted under section 408 of the FFDCA to permit food or feed
bearing the residues of that substance to be introduced into interstate
commerce. Unless the Agency is attempting to regulate the produce as a
pesticide, the issue of post-harvest control is irrelevant. Thus, as
explained in the preceding paragraph, the issue of post-harvest control
is essentially irrelevant to EPA's interpretation that the introduction
of genetic material into a plant that is expected to ultimately produce
a pesticidal effect provides evidence of pesticidal intent, absent any
other indicia to the contrary.
    In addition, EPA offered in 1994 several reasons in support of its
decision to include the genetic material necessary to produce the
pesticidal substance, as well as the pesticidal substance, in the
definition of a plant-pesticide (59 FR 60521). None of them rested on
an assumption that evidence of a pesticidal intent would always be
present after harvest.
    This approach is fully consistent with the Agency's approach to
traditional chemical pesticides. For example, the Agency follows the
fate of traditional chemical pesticides in the soil after the harvest
of the crop and during rotational crop plantings, even when there is no
intent to ``prevent, destroy, repel, or mitigate any pest'' after
harvest or during later plantings. This allows EPA, as required by
FIFRA, to ensure that a pesticide ``when used in accordance with
widespread and commonly recognized practice, . . . will not generally
cause unreasonable adverse effects on the environment'' (see 7 U.S.C.
sections 136a(c)(5) and 136d). This requirement applies even when the
intent of preventing, destroying, repelling or mitigating a pest is no
longer evident; for example, as part of its regulation of pesticides
EPA considers whether pesticide residues or metabolites can migrate
into groundwater, even though there is no intention of obtaining a
pesticidal effect from the presence of these substances in groundwater.
    f. How does the genetic material in the definitions relate to the
whole plant? Comments disagreeing with the inclusion of the genetic
material in the definitions also argued that including the genetic
material ``calls into question EPA's assertion that it has no intention
of regulating the plant, since the `genetic material' will be present
in all parts of the plant and in products derived from the plant.''
    EPA does not believe that including the genetic material in the
definitions calls into question EPA's assertion that it has no
intention of regulating the plant. The comment did not explain how
regulation of the genetic material would lead to regulation of the
whole plant, nor how regulation of genetic material would result in a
different outcome in this regard from regulation only of the substance
produced from the genetic material. EPA clarifies in this document that
plants used as biological control agents are exempt at 40 CFR 152.20.
As a result, EPA is not regulating plants or varieties of plants.
Rather, the Agency regulates the plant-incorporated protectant (i.e.,
the pesticidal substance, the genetic material necessary for the
production of the pesticidal substance, and any inert ingredient) for
use in a particular type of plant (e.g., cotton). To date, EPA has
registered several plant-incorporated protectants, and all have been
registered for use in the crop, rather than plant variety by plant
variety. Moreover, changes to a plant that are unrelated to the plant-
incorporated protectant would not be regulated by EPA, but by the
United State Department of Agriculture (USDA) and the FDA. For example,
changing the color of Bt cotton with the intent of marketing undyed but
nonetheless colored cotton would be evaluated by the USDA and FDA (if
the cottonseed were to be processed for meal or oil in food or feed
uses), even though EPA would evaluate and regulate the effects of the
pesticide, Bt.
    g. Is inclusion of the genetic material in the definitions
consistent with FDA policy? One comment suggested that inclusion of the
genetic material in the definition of plant-incorporated protectant
makes EPA's approach inconsistent with FDA's 1992 Statement of Policy
for Foods Derived from New Plant Varieties (57 FR 22984). The comment
stated that in its 1992 policy, FDA recognized that genetic material is
present in the cells of every living organism and as a result should be
presumed to be ``generally recognized as safe.''
    EPA disagrees that its approach is inconsistent with the 1992
policy issued by FDA. EPA is publishing elsewhere in this issue of the
Federal Register an exemption from the FFDCA section 408 requirement of
a tolerance, for residues in or on food or feed of nucleic acids that
are part of a plant-incorporated protectant. This exemption from FFDCA
section 408 requirements applies to the genetic material necessary for
the production of a pesticidal substance. Part of the rationale
supporting EPA's FFDCA exemption is that nucleic acids are ubiquitous
in nature and have always been present in human food and domestic
animal feed and have been consumed without harm. This rationale is
consistent with FDA's rationale which considers genetic material in
food to be ``Generally Recognized as Safe'' (GRAS). EPA believes its
approach under FFDCA is consistent with FDA's approach under FFDCA.
FIFRA does not automatically exempt substances FDA has classified as
GRAS. Instead, FIFRA requires entities who wish to sell or distribute a
pesticide to either register the pesticide or seek an exemption from
FIFRA requirements prior to such use. For example, garlic used as a
pesticide, was registered until EPA exempted it at 40 CFR 152.25(g) as
a minimum risk pesticide. Any person may petition EPA to establish an
exemption pursuant to FIFRA section 25(b) and FFDCA section 408(d). EPA
will make every effort to expedite its review of such petitions.
    h. Does inclusion of the genetic material in the definitions create
an overly complex regulatory process? One comment stated that inclusion
of the genetic material in the definitions will result in regulatory
uncertainty. The commenter did not explain how inclusion of the genetic
material in the definitions would lead to such uncertainty, and EPA
assumes that this commenter's uncertainty is related to issues posed by
the following questions.

[[Page 37787]]

Are all the genes in the vector used to transform the plant covered by
the definition? If fragments of a gene are present in the plant, but do
not encode a pesticidal substance, are the fragments covered by the
definition? Would a producer need to provide EPA with the number of
copies of the genes that are introduced into the plant? Would the
number of copies be a consideration in the registration process, e.g.,
in determining when a separate, distinct registration is required? How
would changes in regulatory regions affect the status of a registered
product; for example, would a new registration be required for a change
in a promoter?
    EPA does not believe that inclusion of the genetic material in the
definitions will lead to an unnecessary layer of complexity in the
regulatory process. Because the questions posed by the commenter relate
to how EPA views the phrase, genetic material necessary for the
production of the pesticidal substance, EPA responds in Unit
VII.B.8.ii. to the specific questions posed with regard to the genetic
material.
    ii. How is the phrase ``genetic material necessary for the
production'' to be interpreted? EPA's analysis of, and response to, the
specific questions posed with regard to the genetic material follows.
While conceptually parts of this analysis could apply to exempt as well
as non-exempt plant-incorporated protectants, the analysis has
practical relevance only for those plant-incorporated protectants that
are not exempt from FIFRA requirements and are, or are to be,
regulated. For example, the discussion in Unit VII.B.8.ii. on the
Confidential Statement of Formula is only relevant to registered plant-
incorporated protectants.
    a. How does EPA view genetic material introduced into the plant but
not expressed in the plant? One of the questions posed by comment was
whether all the genetic material in a vector used to transform a plant
is considered to be part of a plant-incorporated protectant, even if
some of the genetic material on the vector is not expressed in the
plant and does not play a role in regulation of expression of the
pesticidal substance in the plant. A second question concerned the
status of gene fragments that do not express a pesticidal substance.
    EPA does not intend that all genetic material present in the
genetic insert (e.g., in a vector) introduced into the plant must be
considered part of the plant-incorporated protectant. EPA defines the
term, ``genetic material necessary for the production'' to mean
``genetic material that encodes a pesticidal substance or leads to the
production of a pesticidal substance and regulatory regions.'' To more
fully describe how EPA interprets this language, two scenarios are
discussed.
    The first scenario involves sequences that do not function as
regulatory regions in the plant but do so in other organisms (e.g., in
bacteria). For example, quantities of the genetic material intended to
be introduced into a plant are often prepared through fermentation of
bacteria containing the desired genetic material on pieces of genetic
material called plasmids. To prepare the genetic material, large
quantities of bacteria are grown and the plasmids they contain are
isolated for subsequent introduction into plant cells. One specific
segment of genetic material in these plasmids, called an origin of
replication, controls the replication of the plasmids in the bacterium.
Even though these origins of replication only function as regulatory
regions in bacteria, for technical reasons, they are sometimes part of
the genetic material introduced into the plant along with the genetic
material that encodes for, or leads to the production of a pesticidal
substance. These plasmid origins of replication would not be considered
part of the plant-incorporated protectant, because they do not encode
for a pesticidal substance nor do they lead to production of the
pesticidal substance in the plant, i.e., they do not function as
regulatory regions in the plant. Genetic material necessary for vector
maintenance/transfer in an intermediate host system (e.g., bacteria)
and having no function in the plant would not be considered part of a
plant-incorporated protectant. Sequences that function as regulatory
regions in one organism (e.g., bacteria), but not in the plant are not
``genetic material necessary for the production of the pesticidal
substance'' in the context of a plant-incorporated protectant. These
sequences are not used in a living plant, or in the produce thereof.
    Under the second scenario, a plant-incorporated protectant is
introduced into a plant, but, because of constraints such as the
plant's genetic background, or the point of insertion in the plant's
genome, or accidents of insertion in which an incomplete copy of a gene
is inserted or a regulatory element is lost, the pesticidal substance
is never produced from the genetic material. In the absence of
pesticidal claims, or other indicia of intent, the genetic material
would not be considered part of a plant-incorporated protectant. If,
however, in subsequent generations, the previously silent genetic
material produces the pesticidal substance, and pesticidal claims or
other indicia of pesticidal intent are present, the previously silent
genetic material would be considered, along with the pesticidal
substance, a plant-incorporated protectant.
    b. Will EPA need to know how many copies of a gene are introduced
into a plant? One commenter questioned whether a registrant would need
to provide EPA with the number of copies of the genes that are
introduced into the plant when seeking a registration, and whether a
change in the number of copies present in the plant would trigger a new
registration action.
    The number of copies of the gene(s) introduced into the plant for
the production of the pesticidal substance will not necessarily be a
factor in EPA's determination of whether a new registration is needed.
However, the amount of the pesticidal substance (i.e., levels of
expression) in various plant tissues may be important for an assessment
of potential exposure, and levels of expression may, in some cases, be
related to number of gene copies. Thus, while, in general, changes in
gene copy number would not automatically require an amendment to the
registration, such information may, on occasion, be important in
identification and management of risk. Currently, the Confidential
Statement of Formula, containing information that must be submitted
with each application for registration, describes either the range of
levels of pesticidal substance(s) expected to be expressed in the
plant, or a maximum level expected to be produced by the plant. Should
the level of the pesticidal substance(s) be increased beyond, or
decreased below, the range or the maximum level described in the
Confidential Statement of Formula, EPA believes that the registrant
would generally be required to submit an application for an amended
registration pursuant to 40 CFR 152.44, as the risk assessment
performed for levels listed in the Confidential Statement of Formula
may not be relevant for the new levels. EPA may, in certain cases,
waive this requirement, as described in 40 CFR 152.44(b)(1), or permit
an applicant to modify a registration by notification or non-
notification, in accordance with 40 CFR 152.46. Registrants are
therefore encouraged to consult with the Agency in such cases.
Distribution or sale of products containing levels beyond those
described in the Confidential Statement of Formula may constitute an
unlawful act under FIFRA section 12. This approach for plant-
incorporated protectants is consistent with the Agency's approach for
more traditional

[[Page 37788]]

pesticides (e.g., pesticides synthesized through petroleum chemistry)
with regard to pesticide levels as described in the Confidential
Statement of Formula.
    c. Will EPA need to know about changes in regulatory regions? One
commenter questioned whether changes in regulatory regions would affect
the status of a registered product. For example, would a new
registration be required if one promoter is substituted for another in
an already registered plant-incorporated protectant?
    Regulatory regions such as promoters are part of the definition of
``genetic material necessary for the production'' of a pesticidal
substance. EPA does not anticipate that a new registration, or an
amendment to the existing registration, would always be required with
each modification to a regulatory region. However, EPA believes that in
general, an application for an amended registration would need to be
submitted pursuant to 40 CFR 152.44. Because the Agency has the
discretion to waive this requirement, or to permit an applicant to
modify a registration by notification or non-notification, registrants
are encouraged to consult with the Agency to determine whether the
Confidential Statement of Formula would need to be modified and
consequently a new registration or an amendment to the existing
registration would be required. In some cases a modification to a
regulatory region could result in a new formulation, a new use, or a
new active ingredient. For example, a change in a regulatory region
could result in the pesticidal substance being expressed in a different
plant tissue than where the pesticidal substance had been expressed for
the original registration. In the assessment for the original
registration, risk might only have been evaluated for production of the
pesticidal substance in the leaves of the plant. With the change in
promotor, the pesticidal substance could now be produced in the fruit,
and risk would have to be evaluated for production of the pesticidal
substance in the fruit. Evaluations to assess the potential for risk
associated with such changes typically occur in a new registration
action or an action amending an existing registration.
    d. How will EPA view enzymatic pathways? Several commenters asked
whether EPA would regulate genetic material encoding enzymatic pathways
leading to the production of a pesticidal substance. Another comment
noted that it ``is not clear from either the definition of active or an
inert ingredient how or whether EPA intends to regulate novel gene
products, and the genetic material necessary for their production, that
represents substances such as enzymes, precursors, or intermediates in
biosynthetic pathways that lead to the production of a pesticidal
substance.''
    With regard to the genetic material necessary for the production of
the enzymes that are part of a pathway anabolizing the pesticidal
substance, this genetic material is necessary for the production of the
pesticidal substance, and thus, it is part of the plant-incorporated
protectant.
    With regard to the enzymes, precursors, or intermediates in
biosynthetic pathways necessary for anabolizing the pesticidal
substance, EPA at this time considers them to be part of the plant-
incorporated protectant because the substance is intended to ``ensure
the presence of the active ingredient''--i.e., it is an inert
ingredient. Given that it is theoretically possible that at least some
of these substances could be associated with greater potential for
adverse effects than the actual substance acting as a pesticide (e.g.,
precursors could be more toxic to a nontarget species than the actual
pesticidal substance), EPA has at this time adopted a prudent course.
As the Agency gains greater experience, it may reconsider how it treats
enzymes, precursors or intermediates in anabolic pathways introduced
with the express purpose of producing a pesticidal effect.
    iii. What comments were received on the word ``living'' in the
plant-incorporated protectant definitions? Several comments suggested
that the word ``living'' be deleted from the definition of plant-
incorporated protectant because inclusion of that word in the
definition of plant-incorporated protectant confused the status of
pesticidal substances used for protection against pests post-harvest.
For post-harvest control, a pesticidal substance may be produced in the
plant during the growth portion of its life cycle, not for protection
of the growing plant against pests, but for use during the post-harvest
stage, e.g., to protect the seed or fruit during storage. Another
comment asked for clarification of the status of exudates and materials
that are active in intercellular spaces and/or apoplasts in light of
the clause ``for use in the living plant.''
    a. What does the word ``living'' signify in the plant-incorporated
protectant definitions? EPA believes it is important to include the
word, ``living'' in the definitions to distinguish plant-incorporated
protectants from other types of pesticides. A pesticide is a plant-
incorporated protectant only if the pesticide is intended to be
produced and used in situ in the plant.
    The characteristic of being produced in situ and used in the living
plant makes plant-incorporated protectants unique, particularly with
regard to exposure considerations. Exposure considerations for plant-
incorporated protectants will be dependent to a large part on the
biological characteristics of the living plant in which the plant-
incorporated protectant is produced and used. For example, if a plant
can outcross with nearby relatives, the potential for spread and
increase in the environment of that plant-incorporated protectant
through the spread of pollen must be evaluated.
    Inclusion of the word ``living'' in these definitions serves to
distinguish plant-incorporated protectants from other types of
pesticides. For example, it distinguishes plant-incorporated
protectants from pesticides like pyrethrum isolated from chrysanthemums
and applied to other plants, or pesticides such as the powder, produced
by drying and grinding cayenne peppers, dusted on plants with the
intent of preventing, destroying, repelling or mitigating a pest. A
pesticide that consists of a dead plant or a portion of a dead plant
that is intended to be used to control pests is currently regulated
under FIFRA as subject to 40 CFR parts 153 through 173 and 40 CFR parts
177 through 180. An example of such a pesticide is pyrethrum, isolated
from a plant and applied topically to other plants.
    Because of the importance of distinguishing plant-incorporated
protectants from other types of pesticides, EPA will retain the term
``living'' in the definitions of plant-incorporated protectant and
active ingredient. However, EPA agrees with the commenter that a
pesticidal substance produced in the plant during the growth portion of
its life cycle, not for protection of the growing plant against pests,
but for use during the post-harvest stage, would still be for a
pesticidal activity that should be treated by EPA as a plant-
incorporated protectant and thus subject to 40 CFR part 174. EPA
believes the 1994 Federal Register documents (59 FR 60496, 60519,
60535, 60542 and 60545) clearly indicates that this was EPA's intent.
However, because EPA does not believe it appropriate to delete the term
``living'' from the definition of plant-incorporated protectant, the
Agency clarifies its intent regarding post-harvest control by including
the phrase, ``or in the produce thereof,'' in the definition of plant-
incorporated protectant.
    To reinforce the distinction between plant-incorporated protectants
and other types of pesticides, the word ``living'' is

[[Page 37789]]

also added to the definition of recipient plant. Similarly, to
emphasize that a plant-incorporated protectant is a pesticide produced
and used in situ in a plant, a definition of ``pesticidal substance''
is added at 40 CFR 174.3 and 40 CFR 152.3.
    To further clarify how EPA views a plant-incorporated protectant
when the pesticidal substance is produced, or used, in perhaps only
part of a plant's life cycle, EPA is including the phrase, ``during any
part of the living plant's life cycle,'' in the definition of
pesticidal substance. This phrase clarifies that, if a pesticidal
substance is intended to be produced and used for preventing,
destroying, repelling or mitigating a pest at any time in a plant's
life cycle, the pesticidal substance and the genetic material necessary
for the production of the pesticidal substance are considered a plant-
incorporated protectant, even if the substance is not continually
produced at detectable levels throughout all parts of the plant's life
cycle, or intended to be used in every part of a plant's life cycle for
preventing, destroying, repelling or mitigating a pest. For example,
the pesticidal substance may not be produced in the seedling but is
produced in the tissues of the mature plant for preventing, destroying,
repelling or mitigating a pest. In this situation, the seedling would
be considered to contain a plant-incorporated protectant, because the
pesticidal substance is produced and used during at least one stage of
the plant's life cycle. Further, the genetic material necessary for the
production of the pesticidal substance, which itself falls within the
definition of pesticide under FIFRA section 2(u), and is defined as
part of the plant-incorporated protectant in this rulemaking, would be
present during all phases of the plant's life cycle. Depending on the
biology of the plant, the life cycle could include, for example, a
seed, an embryo, a seedling, a mature or senescent plant.
    EPA has broad authority to regulate a pesticide. For example, the
Agency follows the fate of substances applied as pesticides in the soil
after the harvest of the crop and during rotational crop plantings.
This allows EPA, as required by FIFRA, to ensure that a pesticide does
not cause unreasonable adverse effects even when the intent of
preventing, destroying, repelling or mitigating a pest is not evident.
    A plant's life cycle is considered to be one generation, such as a
seed to seedling to a mature plant and back to a seed for sexually
reproducing plant species, and a vegetative propagule to adult plant to
vegetative propagule for plants reproducing asexually. As in the common
understanding of the term (Ref. 5), a propagule is the part of an
organism that may be disseminated and reproduce the organism.
    b. How does EPA view exudates and materials that are active in
intercellular spaces and/or apoplasts? One commenter requested
clarification on the status of exudates and materials that are active
in intercellular spaces and/or apoplasts. An apoplast is a cell wall
continuum of a plant (Ref. 9). Materials that are active in
intercellular spaces are those active between the cells of the plant
(Ref. 9). Apoplasts and intercellular spaces are within the living
plant. An exudate is composed of substances that were within a plant
and were exuded from the plant, within one of the commonly understood
meanings of the word exude; i.e.,``to give off gradually through
pores'' (Ref. 5). EPA views apoplasts, intercellular spaces and
exudates as properly being part of a living plant as described in the
1994 Federal Register document (e.g., see 59 FR 60534). EPA believes
that this view of a living plant as the sum of its parts is evident in
the preamble discussions of the November 23, 1994 policy (59 FR 60496)
and proposed rule (59 FR 60519). In order to ensure that this view of
the living plant is clear to the regulated community, EPA is adding at
40 CFR 174.3 a definition for the phrase, ``in a living plant,'' which
is part of the definition of ``plant-incorporated protectant.'' The
definition of ``in a living plant'' is intended to clarify that, for
plant-incorporated protectants, the pesticidal substance is part of a
plant-incorporated protectant when it is inside the living plant, on
the surface of the living plant or an exudate given off gradually as
part of a naturally occurring process by a living plant (Ref. 10). The
term ``in a living plant'' is defined at 40 CFR 174.3 to mean ``inside
the living plant, on the surface of the living plant, or as an exudate
from the living plant.'' For the purposes of this rule, EPA defines an
``exudate'' as ``a substance gradually discharged or secreted across
intact cellular membranes or cell walls and present in the
intercellular spaces or on the exterior surfaces of the plant.'' EPA
believes these actions address the commenter's request for
clarification.
    Sap or other material that is collected through mechanical means
from a plant (e.g., sap exuded from a gash resulting from intentional
wounding in the bark of a tree) by a human and sold or distributed as a
pesticide does not fall within the definition of ``exudate'' because it
was not given off gradually as part of a naturally occurring process
from the plant. Rather it results from the wounding of the plant.
Materials such as maple syrup may meet the definition of ``produce
thereof'' if a substance within the syrup is intended to serve a
pesticidal purpose by protecting the syrup after it has been collected
from the tree. However, sap collected by mechanical means sold or
distributed as a pesticide to protect some other produce or thing would
be subject to regulations found in 40 CFR parts 150 through 173 and 40
CFR parts 177 through 180, rather than 40 CFR part 174.
    iv. What other modifications have been introduced into the
definitions? EPA, for purposes of clarity, introduces two other
modifications to the plant-incorporated protectant definitions. First,
EPA modifies the definition of ``plant-incorporated protectant'' for
greater clarity, to include the concept of intention to use in a living
plant as well as to be produced in a living plant, and to include the
concept of the produce thereof, for similar reasons as discussed in
Unit VII.B.8.iii.a. ``Produce thereof'' is defined to mean, when used
with respect to plants containing plant-incorporated protectants only,
a product of a living plant containing a plant-incorporated protectant,
where the pesticidal substance is intended to serve a pesticidal
purpose after the product has been separated from the living plant.
Examples of such products include, but are not limited to, agricultural
produce, grains and lumber. Products such as raw agricultural
commodities bearing pesticide chemical residues, are not ``produce
thereof'' when the residues are not intended to serve a pesticidal
purpose in the produce.
    Second, the definition of living plant at 40 CFR 174.3 and 40 CFR
152.3 is revised to read:
    Living plant means a plant, plant organ or plant part that is
alive, viable or dormant. Examples of plant parts include, but are
not limited to, seeds, fruits, leaves, roots, stems, flowers and
pollen.

    v. What is an inert ingredient for this type of pesticide? EPA
originally proposed to define inert ingredients for plant-incorporated
protectants 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'' (59
FR 60521).
    In this section, EPA focuses on selectable markers. EPA discusses
other inert ingredients in Unit VIII.B.8.ii.d. Therefore, throughout
this discussion,

[[Page 37790]]

EPA uses the phrases ``substances used to confirm or ensure the
presence of a plant-incorporated protectant in a plant'' and
``selectable markers'' interchangeably. Selectable markers are genetic
material introduced into the plant or plant cells concomitant with the
genetic material that confers the desired trait (e.g., a pesticidal
trait). A selectable marker provides a means of distinguishing and
selecting plants or plant cells that have successfully incorporated the
genetic material conferring the desired trait from the vast majority of
plants or plant cells that have not. For example, the selectable marker
may endow the recipient cell with the ability to resist a lethal agent
and the selection process may depend upon the cells that acquired the
introduced genetic material being resistant to the lethal agent. When
the cells are exposed to the lethal agent, the cells that did not
incorporate the genetic material are killed, while the cells that did
incorporate the introduced genetic material survive. When the
researcher uses the toxic agent to select those cells that can resist
the lethal agent, the researcher also selects the cells that acquired
the desired trait (e.g., a pesticidal trait).
    In response to its proposed rule in 1994, EPA received several
comments suggesting that plant-incorporated protectant inert
ingredients that had been reviewed by FDA should be exempt from EPA
review. One commenter, noting that the 1992 FDA policy statement (57 FR
22984) addresses the relevant food safety issues associated with
selectable markers, suggested these should only be reviewed by FDA.
Other commenters suggested that the genetic material necessary for the
production of the pesticidal substance be defined as an inert
ingredient for plant-incorporated protectant, along with selectable
markers, rather than as an active ingredient. Yet other commenters
suggested that EPA broaden its original proposed rule to include ``a
substance used to assist in the identification of plants or plant cells
containing the active ingredient.'' Another commenter suggested that
marker genes and their products should be considered active ingredients
in order to ensure some type of ``safety review'' of the marker genes.
Another commenter urged EPA to make clear that plant-incorporated
protectant inert ingredients are excluded from EPA's ``new inerts''
policy (52 FR 13305, April 22, 1987) which requires testing and EPA
approval of inerts not already on the Agency's approved inerts list.
    During development of the final rule, EPA reconsidered its 1994
proposed rule and published a supplemental document on July 22, 1996 in
the Federal Register (61 FR 37891), discussing the Agency's treatment
of inert ingredients. In the supplemental document, EPA discussed
several considerations that argued against treating selectable markers
as inert ingredients, including: the unique nature of plant-
incorporated protectants and substances such as selectable markers; the
function of selectable markers in plants; and the effects of selectable
markers on the performance of the plant-incorporated protectant. The
Agency pointed out that substances such as selectable markers are
intentionally introduced into plants to aid in the selection of plants
or plant cells that contain the desired genetic material necessary for
producing the plant-incorporated protectant and consequently are
typically introduced into the plant at the same time as the active
ingredient (61 FR 37892-37893, July 22, 1996). Because the requisite
intent to include such substances in the pesticide product is present
in the use of selectable markers in plant-incorporated protectants, the
markers would be considered to be an inert ingredient under the
Agency's traditional interpretation of that term. But EPA also noted
that selectable markers do not have pesticidal properties themselves,
are not necessary for the plant-incorporated protectant to function in
the plant and are usually used only once in the early stages of product
development, and are of no use in modifying or enhancing the pesticidal
activity of the plant-incorporated protectant. EPA also speculated that
the marker genes could be lost from the plant during subsequent
breeding with no effect on the active ingredient, and provided the
public an additional opportunity to comment on how such substances
should be viewed under FIFRA (61 FR 37893, July 22, 1996).
    Many of the comments EPA received in response to the supplemental
document recommended that selectable markers not be considered inert
ingredients. Several of these commenters supported their recommendation
by noting that it would reduce the ``potential for duplication with
reviews by the FDA,'' which already reviews the food and feed safety of
selectable markers. One commenter, who supported a decision not to
consider all selectable markers as inert ingredients, nevertheless
noted that the commenter was ``particularly concerned about adverse
environmental impacts of such substances on non-target organisms,
particularly salmon or members of aquatic ecosystems upon which their
survival depends.'' Another commenter, while concurring that EPA should
not regulate selectable markers as inert ingredients, suggested that
EPA explore in greater detail the ramifications of using herbicide
tolerant traits as selectable markers. This commenter was concerned
that potentially widespread use of herbicide resistance traits as
selectable markers ``may tempt unscrupulous farmers to apply the
herbicide to crop plants in the field, even though the herbicide is not
registered for use with the crop plant.''
    To determine how to proceed, the Agency considered the comments
received in response to both its original proposed rule and the
supplemental document, and the degree to which they addressed the
considerations laid out in the supplemental document. This included
comments on the Agency's treatment of individual selectable markers, as
well as the Agency's overall approach to inert ingredients. None of the
comments, however, provided information or analyses that definitively
resolved the question one way or another.
    Although the majority of commenters supported a decision not to
treat selectable markers as inert ingredients, most of these comments
appeared to be based on concerns over the potential for duplicative
oversight between EPA and FDA. In addition, several comments received
in response to both notices raised human health and environmental
safety issues surrounding certain selectable markers, such as genes
coding for herbicide or antibiotic resistance, and supported some
government oversight to ensure that a ``safety review'' was conducted.
    With respect to the potential for duplicative oversight, EPA
acknowledges that some degree of overlapping jurisdiction with FDA
currently exists in that both agencies share responsibility for
evaluating different aspects of a selectable marker. As previously
explained, both agencies have agreed that EPA will address under its
regulatory jurisdiction the food safety issues associated with the
pesticide, including selectable markers. Any food safety questions
beyond those associated with the pesticide, such as those raised by
unexpected or unintentional compositional changes, are under FDA's
jurisdiction (57 FR 22984 and 59 FR 60514).
    Bearing in mind the concerns with respect to duplicative review,
EPA considered whether relinquishing

[[Page 37791]]

jurisdiction to FDA would best address the health and safety concerns
raised. Although many of the issues with respect to the safety of the
food or the development of antibiotic resistance are within FDA's
traditional purview and expertise, the issues with respect to impact on
non-target organisms and ecosystems are ones with which EPA has greater
experience in regulating under FIFRA. And given EPA's longstanding
expertise in considering food safety concerns under the FFDCA, it was
determined that on balance, the totality of the concerns could be
better addressed by regulating under both FIFRA and the FFDCA than by
regulating under the FFDCA alone. These considerations thus weighed in
favor of considering selectable markers to be inert ingredients in a
plant-incorporated protectant. Moreover, EPA and FDA can work together
to minimize the impacts arising from any overlap in jurisdiction, and
will coordinate extensively towards that end.
    As EPA explained in the 1996 supplemental document, FIFRA and FFDCA
contain only general definitions of the relevant terms. FIFRA section
2(u) defines a ``pesticide'' as any substance or mixture of substances
intended ``for preventing, destroying, repelling, or mitigating any
pest'' or ``for use as a plant regulator, defoliant, or desiccant'' or
``any nitrogen stabilizer (7 U.S.C. 136(u)).'' An ``active ingredient''
is defined as ``in the case of a pesticide other than a plant
regulator, defoliant, desiccant, or nitrogen stabilizer, an ingredient
which will prevent, destroy, repel, or mitigate any pest'' (7 U.S.C.
136(a)). FIFRA defines ``inert ingredient'' to mean ``an ingredient
which is not active'' (7 U.S.C. 136(m)). Under the FFDCA, a substance
is a ``pesticide chemical'' if it is ``a pesticide within the meaning
of [FIFRA], including all active and inert ingredients of such
pesticide'' (21 U.S.C. 321(q)(1)).
    Although the statutory definitions provide some guidance, they do
not definitively resolve whether the Agency should define substances
intentionally introduced into the plant with the active ingredients as
inert ingredients. EPA's current pesticide regulations, along with
EPA's past practice and interpretation of those regulations, however,
although not specifically addressing selectable markers, do provide
considerable insight into the issue of inert ingredients. EPA's
longstanding regulatory definition of ``inert ingredient'' includes as
an inert ``any substance (or group of structurally similar substances
if designated by the Agency), other than an active ingredient, which is
intentionally included in a pesticide product'' (40 CFR 152.3(m); see
also 40 CFR 158.153(f)). A ``pesticide product'' is defined by
regulation to be ``a pesticide in the particular form (including
composition, packaging, and labeling) in which the pesticide is, or is
intended to be, distributed or sold'' (40 CFR 152.3(t)).
    These definitions capture as inert ingredients, all those
substances that are intentionally included in the pesticide product
that are not active. Further, EPA has consistently interpreted these
definitions to include substances that serve no useful purpose in the
product. The Agency has never required that inert ingredients have
pesticidal properties themselves, nor has the Agency required that
inert ingredients modify or enhance the pesticidal activity of the
pesticide although inert ingredients are often used for at least one of
these purposes. In fact, the Agency has indicated on several occasions
that inert ingredients are generally not ``pesticidally active'' (See,
e.g., Inert Ingredients in Pesticide Products; Policy Statement, (52 FR
13305, April 22, 1987); see also Pesticide Registration Procedures;
Pesticide Data Requirements, (53 FR 15952, 15963, May 4, 1988)). Thus,
the essential criterion that the Agency has used to determine whether
an ingredient is an ``inert'' is the intent of the producer to include
the substance in the pesticide product.
    In the case of plant-incorporated protectants, the Agency has
emphasized in both the 1994 proposed rule and the 1996 supplemental
document that substances ``such as selectable markers are intentionally
introduced into plants'' (61 FR 37892-37893; see also 57 FR 60521). In
the 1996 supplemental document, the Agency pointed out that substances
such as selectable markers are intentionally introduced into plants to
aid in the selection of plants or plant cells that contain the desired
genetic material necessary for producing the plant-incorporated
protectant and consequently are typically introduced into the plant at
the same time as the active ingredient (61 FR 37892-37893). Because the
requisite intent to include such substances in the pesticide product is
present in the use of selectable markers in plant-incorporated
protectants, the markers would be considered to be an inert ingredient
under the Agency's traditional interpretation of that term. No
commenters provided information or analyses that would contradict this
interpretation or that would lend support to the other considerations
laid out in the 1996 notice arguing against treating these markers as
inert ingredients.
    Moreover, since the 1994 proposed rule and 1996 supplemental
document, EPA has had experience with selectable markers in the
registration of several plant-incorporated protectants that is relevant
to the considerations presented in the 1996 supplemental document. For
example, contrary to the speculation in the 1996 document, some
selectable markers are not used only once, i.e., to distinguish the
cells transformed with the pesticidal trait from those that had not
acquired the trait. Rather, the ability to resist the lethal agent is
being used during the breeding process to develop commercially viable
lines as a phenotypic identifier to select progeny plant lines having
the desired pesticidal trait. In such cases, the role played by the
selectable marker is somewhat different than was considered in 1996. In
addition, in the interim, EPA has become aware of other substances that
could be used as selectable markers, e.g., green fluorescent protein
(Ref. 11), and while EPA can make some prediction about the potential
interactions with and effects on the pesticidal substance of currently
used selectable markers, e.g., antibiotic and herbicide resistance, it
cannot do so for selectable markers that may be developed and used in
the future.
    In light of this experience, and in light of the concerns raised by
some of the commenters regarding safety issues associated with the use
of selectable markers, the Agency believes it prudent to consider these
substances to be inert ingredients and to continue to assess their
safety. EPA believes that these considerations outweigh the
considerations discussed in the 1996 supplemental document, arguing
against treating such substances as inert ingredients. Moreover, to
ensure that health and safety issues are addressed by the Agency with
the greatest technical expertise without duplicative oversight, EPA and
FDA will work closely to address areas of potentially overlapping
jurisdiction, and to share expertise in reviews. Consequently, for
these reasons, as well as for the reasons outlined in the 1994 proposed
rule, the Agency has determined that it will adopt the definition it
proposed in 1994 with minor modification.
    One comment asked whether EPA intended to treat the enzymes leading
to the production of the pesticidal substance as inert ingredients. As
noted in Unit VII.D.8.ii.d., EPA will consider the enzymes, precursors,
or intermediates in biosynthetic pathways necessary for anabolizing the
pesticidal

[[Page 37792]]

substance to be an inert ingredient of the plant-incorporated
protectant.
    One comment suggested that in ``anticipation of inerts that would
be introduced to perform other nonpesticidal functions, the restrictive
language should be removed and the relationship to the active
ingredient characterized as intentionally introduced into a living
plant in association with the active ingredient.'' EPA disagrees. The
commenter's suggested language is so broad that it would cover
introduced genetic sequences that EPA considers to be appropriately
within USDA's or FDA's sphere, e.g., modifications to the starch
content of a potato. As noted in the preceding paragraph, EPA
anticipates that as it gains experience, it may change its view of what
is appropriately an inert ingredient for plant-incorporated
protectants, although the Agency does not anticipate that it would
subsume in its definition all modifications affecting substances that
have traditionally been in USDA's or FDA's purview. EPA acknowledges
that any modification of the definition of inert ingredient for plant-
incorporated protectant would be made through rulemaking.
    With regard to the comment urging EPA to make clear that plant-
incorporated protectant inert ingredients are excluded from EPA's ``new
inerts'' policy (52 FR 13305), EPA has created 40 CFR part 174, subpart
X, specifically for inert ingredients for plant-incorporated
protectants. Inert ingredients in 40 CFR part 174, subpart X, are not
part of EPA's ``new inerts'' policy (52 FR 13305) per se; however EPA's
approach for plant-incorporated protectants is consistent with the
policy.
    Several commenters requested that EPA consider the genetic material
necessary for the production of the pesticidal substance to be an inert
ingredient. For reasons described in Unit VII.B.8.i., EPA will not
consider this genetic material to be part of the inert ingredient.

C. Clarification of Exemption at 40 CFR 152.20; Status of Plants Used
as Biological Control Agents with Regard to FIFRA Requirements

    Most comments supported EPA's proposal to clarify that, although
plants used as biological control agents will remain exempt under 40
CFR 152.20, plant-incorporated protectants will not fall within that
exemption, but will be subject to FIFRA requirements, including the
regulations codified at 40 CFR part 174. However, some commenters
argued that the ability to resist pests is a characteristic of the
plant and should not for regulatory purposes be separated from the
plant itself. Another comment opposed exempting plants from FIFRA
requirements and argued that the definition of biological control agent
at 40 CFR 152.3 does not apply to plants. This commenter argued that
the definition at Sec. 152.3 was meant to apply to classical biological
control agents--predaceous and parasitic arthropods--whose sole use is
to control pests. The commenter further argued that plants cannot be
considered classical biological control agents because the primary use
of plants is not pest control but yield of a product; pest control for
plants is merely an attribute which helps to achieve yield.
    With regard to the comment concerning ``classical biocontrol
agents,'' EPA recognizes that classical biocontrol generally involves
the use of one organism such as a predaceous or parasitic arthropod to
protect another organism such as a plant (Refs. 10 and 12). Plants were
not specifically addressed in the regulation EPA published in the June
2, 1982, Federal Register document (47 FR 23928) that exempted, under
FIFRA section 25(b)(1), most biological control agents from the
requirements of FIFRA. There are, however, circumstances in which
plants are used as ``classical'' biological control agents analogous to
the use of predaceous and parasitic arthropods to protect other
organisms. For example, organic gardeners use living plants, such as
marigolds, chrysanthemums and geraniums, in their gardens with the
intent of protecting other plants, such as vegetable plants. This type
of plant for this type of use clearly meets the 40 CFR 152.3 definition
of biological control agent because it is a ``living organism applied
to or introduced into the environment that is intended to function as a
pesticide against another organism declared to be a pest by the
Administrator.''
    Plants, when humans intentionally use them for preventing,
destroying, repelling or mitigating a pest, meet the FIFRA section 2(u)
definition of pesticide, and thus are pesticides. A living plant that
is intended to have a pesticidal effect meets the definition at 40 CFR
152.3 of biological control agent because it is a ``living organism
applied to or introduced into the environment that is intended to
function as a pesticide against another organism declared to be a pest
by the Administrator.'' In 1994, EPA advised the public that the Agency
considered plants that protect themselves against pests to fall within
the definition of biological control agents (59 FR 60496). This
statement created some uncertainty regarding the regulatory status of
such plants under FIFRA, in part because such plants were not
explicitly addressed in the preamble to either the proposed or final
rule establishing the exemption at 40 CFR 152.20 (46 FR 18, 322, March
24, 1981; 47 FR 23928, June 2, 1982). Today's action clarifies the
status of such plants. The plants themselves will remain exempt, but
EPA will continue to regulate the pesticidal substances in such plants
under FIFRA and the FFDCA, even when they are intended to be used in
the exempt plants.
    Moreover, the commenter fails to provide any meaningful distinction
between ``predaceous and parasitic arthropods whose sole use is to
control pests'' and plant-incorporated protectants. All agricultural
use pesticides are, in some sense, applied to crops to increase yields,
or to otherwise obtain the maximum profit from the crop. It has been
EPA's experience that farmers do not apply pesticides simply to kill
insects without also intending to affect yield, or to otherwise protect
or increase a crop's profitability.
    EPA also disagrees with the comment that, for regulatory purposes,
a characteristic of the plant should not be separated from the plant
itself. EPA believes that its decision to regulate plant-incorporated
protectants, while exempting the plants themselves is an appropriate
regulatory approach because it allows the Agency to focus its oversight
on the ``pesticidal'' characteristics of the plant, and any associated
risks. In addition, this approach is consistent with the Agency's long-
standing regulation under FIFRA.
    Under existing regulations, although the plant itself is exempt
from FIFRA requirements, substances that are extracted from plants and
used as pesticides are not similarly exempted. For example,
chrysanthemums produce pyrethrum, a substance that has insecticidal
activity. Chrysanthemums that produce pyrethrum are exempt from
regulation when used as biological control agents (i.e., living
chrysanthemums), but pyrethrum itself as the pesticidal substance, is
not exempt when it is extracted from chrysanthemum plants and applied
to other plants as a pesticide. This distinction is reasonable in light
of the potential for increased and unique exposures due to large-scale
application of extracted pyrethrum to plants that do not naturally
produce it. The use of extracted pyrethrum as an insecticide can
involve exposure to the pesticide over large acreage, whereas the
exposure

[[Page 37793]]

associated with pyrethrum produced by living chrysanthemum plants would
not be expected to reach such proportions. In addition, application of
pyrethrum beyond the environment in which it is naturally produced
(i.e., beyond the living chrysanthemum plant) could result in new or
unique exposures of nontarget organisms, including humans.
    With the development of modern biotechnology, the number of such
plants sold with the intention that the pesticidal substances in the
plant function while in the plant, rather than extracting the
pesticidal substance from the plant, have dramatically increased. But
of greater regulatory significance, with these techniques, a plant can
be endowed with properties that were previously not possible; for
example, the ability to produce pyrethrum can be given to a crop plant
such as corn. Different exposure considerations would exist for
pyrethrum in corn than for pyrethrum in chrysanthemums. Given that
millions of acres are planted to corn in the US, some of the exposure
considerations of pyrethrum in corn might be more analogous to the
considerations for exposure from sprayed pyrethrum than to
considerations for pyrethrum in chrysanthemums.
    Similarly, potato, cotton and corn plants have recently been
engineered to produce the endotoxin from the bacterium, Bacillus
thuringiensis (Bt). EPA assessed the risk of these Bt-based plant-
incorporated protectants in a manner consistent with EPA's treatment of
Bt in other formulations. Bt is regulated under FIFRA when formulated
in products to be dusted/sprayed on plants for protection against
pests. Many of the risk considerations evaluated for Bt used as a
plant-incorporated protectant are the same considerations evaluated for
Bt sprayed or dusted on plants as a pesticide.
    In this final rule, EPA clarifies that plants that humans use with
the intention of controlling pests will remain exempt from FIFRA
requirements pursuant to the exemption at 40 CFR 152.20, but that the
pesticidal substances, and inert ingredients contained in the plants,
remain subject to the requirements of FIFRA, as codified at 40 CFR part
174. The regulatory text at Sec. 152.20 is also modified to make clear
that the exemption for plants used as biological control agents applies
to living plants and does not apply to plants or plant parts that have,
for example, been dried or processed for use as pesticides. An example
of this latter type of pesticide would be the powder, produced by
drying and grinding cayenne peppers, dusted on plants with the intent
that it would protect the plants against disease. This type of
pesticide does not meet the definition of biological control agent and
is not exempted at Sec. 152.20. Processed plants or plant parts used as
pesticides are currently subject to the regulations at 40 CFR parts 150
through 173 and 40 CFR parts 177 through 180.
    EPA believes it is appropriate to exempt the living plant from
FIFRA requirements. The Agency believes its focus on the plant-
incorporated protectant rather than on the plant allows it to ensure a
low probability of risk to humans and the environment, while imposing a
minimum burden on the development of plants containing novel plant-
incorporated protectants and conserving limited Agency resources. Had
EPA chosen to regulate the plant, it would have issued registrations
for plant varieties. By focusing on plant-incorporated protectants, in
contrast, EPA can issue a registration for use of the plant-
incorporated protectant within a larger grouping, such as a crop. This
allows the Agency to focus its resources on evaluating the pesticidal
properties of the plant, rather than on other properties of the plant.
EPA believes that the clarification in this rule today that it will not
regulate plants per se, and the exemption it is issuing today in
another section of this document, and in a companion document published
elsewhere in this issue of the Federal Register, limit EPA's effect on
plant breeding and allow most aspects of plant breeding to be pursued
without EPA regulation.
    However, EPA also believes it is appropriate to exclude certain
plant-incorporated protectants from the exemption at 40 CFR 152.20.
Section 25(b) requires the Agency to support its determination that a
class of pesticides meet the standard for an exemption. EPA's
assessment supporting the 1982 exemption did not encompass all of the
plant-incorporated protectants being developed and marketed today, and
the Agency could not rely on those assessments to support such an
exemption. As noted above, with modern biotechnology, a plant can be
endowed with properties that were not possible in 1982, and different
exposure and hazard considerations would exist for such plants. Nor
could the Agency develop sufficient evidence to maintain a categorical
exemption for all plant-incorporated protectants, given all of the
possible genetic modifications that can be achieved with these
techniques, even if the Agency were inclined to do so. As an initial
matter, Agency could not anticipate all potential modifications, let
alone develop a risk assessment for all potential intended, and
unintended, effects from such modifications.
    EPA is exempting those plant-incorporated protectants for which the
Agency can support the necessary findings, based on the available
scientific evidence and the Agency's technical expertise. For example,
the exemptions established in another section of this document, and in
a companion document published elsewhere in this issue of the Federal
Register, encompass the chrysanthemum discussed above, as long as it
meets the exemption criteria, even though it contains a plant-
incorporated protectant. As the Agency's base of knowledge and
experience increases, exemptions for additional categories of plant-
incorporated protectants may be warranted. But until then, the Agency
believes that a case-by-case review of plant-incorporated protectants
not specifically exempted in this rule, is necessary to ensure that
such products can be sold and used without generally posing
unreasonable adverse effects on the environment. Case-by-case review
will also allow the Agency to increase the available body of scientific
knowledge and experience to determine whether additional exemptions are
warranted. In addition, any person may petition EPA to establish an
exemption pursuant to FIFRA section 25(b) and FFDCA section 408(d). EPA
encourages additional exemptions when supported by scientific data and
will make every effort to expedite its review of such petitions,
consistent with the requirements of these sections.

D. Exemption of Plant-Incorporated Protectants Derived Through
Conventional Breeding from Sexually Compatible Plants

    This rule exempts from FIFRA requirements, except for the adverse
effects reporting requirements at 40 CFR 174.71, plant-incorporated
protectants derived through conventional breeding from sexually
compatible plants.
    In 1994, EPA proposed to exempt from all FIFRA requirements, except
for the adverse effects reporting requirements now at 40 CFR 174.71, a
category of plant-incorporated protectants based on the premise that
new exposures would be unlikely if the genetic material leading to the
production of the plant-incorporated protectant is derived from a plant
closely related to the recipient plant. EPA offered three options for
defining plant-incorporated protectants derived from plants closely
related to the recipient plant. All of the options were

[[Page 37794]]

based on the concept of source organism and the phylogenetic
relatedness of the genetic donor and recipient. None of the three
options was based on the process by which a plant-incorporated
protectant was introduced into the recipient plant. Option 1, based
upon sexual compatibility, was EPA's preferred option (59 FR 60534).
Under this option, plant-incorporated protectants derived from plants
sexually compatible with the recipient plant would be exempt from FIFRA
regulation. Options 2 and 3 used taxonomy (genus) to define closely
related plants, either exclusively (Option 2) or in conjunction with
sexual compatibility (Option 3). The Agency also requested comment on
the utility of an exemption criterion based on the process (e.g., rDNA)
used to introduce the plant-incorporated protectant into a plant (59 FR
60514 and 60530). This approach was discussed by the SAP Subpanel and
BSAC Subcommittee at the joint meeting of these scientific advisory
groups held on January 21, 1994. In this approach, plant-incorporated
protectants developed through techniques other than those of modern
biotechnology would be exempted, e.g., those developed through
conventional plant breeding would be exempted. Categories of those
plant-incorporated protectants that were not exempted by this criterion
could subsequently be considered for exemption on the basis of risk
potential.
    The joint subcommittee/subpanel report recommended such a
``process-based'' approach on the following three considerations.
First, the National Institutes of Health Guidelines for Research
Involving Recombinant DNA Molecules established a precedent that has
worked well. Second, although new techniques, such as rDNA, are more
precise than conventional plant breeding, it is possible to make with
rDNA novel genetic modifications never before possible. The novel
combinations possible with modern genetic techniques create
uncertainties about how the gene will function and how its products may
affect the plant's phenotype and its impact upon the environment and
human health. Third, establishing rDNA methodologies as a criterion for
oversight may give the public more confidence that risk potential is
being evaluated. As a result, approved products may move to the
marketplace more easily (Ref. 15).
    The majority of the comments on the proposed exemption based on the
degree of relatedness between the donor and recipient plants favored
the option based on sexual compatibility between the donor and
recipient plants (preferred option in the November 23, 1994 Federal
Register document (59 FR 60533)). The Agency did not receive any
comments that favored the option based on taxonomy, Option 2. Although
several comments favored the option that relied on both taxonomy and
sexual compatibility, Option 3, EPA also received comments that
expressed reservations about using taxonomy to describe a close degree
of relatedness for regulatory purposes.
    EPA received numerous comments supporting an approach based on
process, i.e., that those plant-incorporated protectants introduced by
rDNA would be regulated. The arguments advanced by these commenters can
be represented by the comment that:
    genetic engineering (particularly recombinant DNA [rDNA]
methodologies), represent a fundamental technical advance over
traditional plant breeding in the ability to manipulate plants
genetically. Genes which code for production of plant-pesticides can
be readily turned `on' or `off' to dramatically increase the
existing levels of plant-pesticides within plants, turning plants
into pesticide factories and delivery systems. . . . given the fact
that rDNA technologies represent such a fundamental technical
advance over plant breeding, and given that plant-pesticides are by
their very nature toxic substances, all plant-pesticides produced
via rDNA methodologies should undergo some form of review under both
FIFRA and FFDCA . . . . (Ref. 13).

    Several letters described quantitative changes in the levels of
plant-incorporated protectants as specific instances in which the
commenter believed risk would be better addressed by an approach based
on process.
    Some comments urging regulation based on whether rDNA had been used
to introduce the plant-incorporated protectant supported exempting
conventional breeding. One commenter, for example, stated that
pesticidal products that ``are introduced by traditional breeding pose
generally low risk and should be exempt'' (Ref. 14).
    Based on the advice of the BSAC and SAP at the joint meeting held
January 21, 1994, and the comments received in response to the November
23, 1994 Federal Register document, EPA has determined that it is
appropriate to issue a limited exemption for those plant-incorporated
protectants derived through conventional breeding from plants sexually
compatible with the recipient plant. In a companion document published
elsewhere in this issue of the Federal Register, EPA solicits public
comment on alternate options for the category of plant-incorporated
protectants derived through modern biotechnology, e.g., rDNA
techniques, from plants sexually compatible with the recipient plant.
The Agency is considering these options in response to the public
comment received on its earlier proposals. One of these options would
establish notification procedures, and as the public has not had an
opportunity to comment on either the procedures themselves, or the
criteria on which EPA would base its regulatory decisions, the Agency
believes it is appropriate to seek additional public comment prior to
adopting a particular option. In addition, as these alternatives would
distinguish between categories of plant-incorporated protectants based
solely on the processes by which they are derived, the public will also
have an opportunity to present additional comments on whether this is
an appropriate distinction for regulatory purposes.
    1. What is the language of the exemption? In this action, EPA is
exempting only a subgroup of the category it proposed to exempt in
1994, those plant-incorporated protectants derived through conventional
breeding from sexually compatible plants.
    i. Why is sexual compatibility an appropriate standard? EPA
believes sexual compatibility is an appropriate standard because
sexually compatible plants share a common pool of genetic material,
even though there may be some variability among plants in sexually
compatible populations. Sexual compatibility, the ability to produce
viable offspring, is only possible in nature for plants that possess
many traits in common. Traits, and the genetic material encoding them,
can be passed through sexually compatible plant populations by
hybridization, and the mixing of genetic material that occurs through
this process of mating tends to a situation where the members of
sexually compatible population have similar traits and similar genetic
material. This is particularly true with crop plants where generations
of selection and breeding have tended to decrease the total genetic
variability in many agronomic species. Sexually compatible thus
presents a natural grouping of plants which can be readily described
and used as a regulatory standard, and about which a large amount of
information exists in the scientific literature. This information can
be used in assessing risk.
    Using sexual compatibility as a standard affords a clear
delineation of whether a plant-incorporated protectant meets the
conditions of the exemption. In most cases, whether two plants are
sexually compatible is known; thus, testing to determine whether the
plants

[[Page 37795]]

are sexually compatible is not likely to be necessary. If, in rare
cases, it is not known whether two plants are sexually compatible, the
means of determining sexual compatibility is straightforward and
simple. Sexual compatibility is empirically demonstrable. EPA believes
that the criterion of sexual compatibility provides a high level of
regulatory clarity and the greatest ease of implementation, while at
the same time presenting the lowest probability of novel dietary
exposure. This standard allows the public, industry, and EPA to easily
and readily identify those plant-incorporated protectants that meet the
criterion of being derived from plants closely related to the recipient
plant.
    a. Why is sexual compatibility limited to conventional breeding? As
explained in a companion document published elsewhere in this issue of
the Federal Register, EPA is soliciting additional comment on the
various options it is considering in response to the significant
comments it has received raising issues specific to plant-incorporated
protectants derived through genetic engineering. Because none of the
comments raised significant issues relative to plant-incorporated
protectants derived through conventional breeding, the Agency is
finalizing its proposals with respect to this subgroup of products.
Therefore, EPA includes in the definition of sexually compatible at 40
CFR 174.3 the clause ``through conventional breeding.'' EPA also
provides a definition of conventional breeding that equates it to the
creation of progeny through either: The union of gametes, i.e.,
syngamy, brought together through processes such as pollination,
including bridging crosses between plants and wide crosses; or
vegetative reproduction. Conventional breeding does not include use of
any of the following technologies: Recombinant DNA; other techniques
wherein the genetic material is extracted from an organism and
introduced into the genome of the recipient plant through, for example,
micro-injection, macro-injection, micro-encapsulation; or cell fusion.
EPA believes that this definition addresses the recommendation of the
SAP/BSAC at the January 21, 1994 joint meeting that ``the Agency define
methodologies in a way that clearly delineates to the scientific
community and the public what is and is not included in the regulatory
scope'' (Ref. 15).
    In the 1994 proposed rule (59 FR 60524) EPA states that its
proposed rule is based on ``experience with the exposure of human
populations to crops developed through the breeding process, i.e.,
crops developed through 100 years of scientific breeding among sexually
compatible plant populations using Mendelian genetics.'' In its 1994
proposed rule, EPA calls this type of breeding, ``traditional
breeding'' (see e.g., 59 FR 60519). When the Agency determined that it
would exempt a subgroup of plant-incorporated protectants in the
sexually compatible grouping while allowing additional comment on how
EPA should treat those plant-incorporated protectants introduced into
the plant through the techniques of modern biotechnology, EPA chose to
describe the exempt group in the most straightforward manner; i.e.,
those derived through breeding. Recognizing that many consider the
modern techniques of biotechnology as simply an extension of breeding
techniques, EPA determined that an adjective was needed to modify the
word ``breeding'' to adequately describe the exempt group. Although the
Agency used the word ``traditional'' in its 1994 proposed rule, EPA
chose the word ``conventional'' to describe this type of breeding in
this rule because the SAP/BSAC in their report of the January 21, 1994,
joint meeting used the adjective ``conventional'' in its advice to EPA
(Ref. 15), and the word ``conventional'' might more readily connote
techniques such as wide crosses.
    b. Why is conventional breeding described by processes such as
pollination and vegetative reproduction? One comment received on the
1994 proposed rule suggested that there is ambiguity in the proposed
regulatory language at 40 CFR 174.5(a) in the November 23, 1994,
Federal Register document (59 FR 60535) about whether plant-
incorporated protectants that are ``native'' to a food crop would meet
the criteria of exemption.
    Because of the use of the word ``food'' in the comment, it was not
clear whether the comment is directed toward EPA's proposed exemption
under FIFRA or that under FFDCA for residues of plant-incorporated
protectants derived from sexually compatible plants. EPA assumes this
comment is directed at both exemptions, and that the commenter's
suggestion is that EPA ensure that the regulatory language exempts from
FIFRA requirements, those plant-incorporated protectants that normally
occur in a plant (i.e., are ``native'' to the plant) and will be used
in that plant. For example, if corn normally produced a plant-
incorporated protectant, the regulatory text should be clear that the
plant-incorporated protectant would be exempt when produced and used in
corn. EPA believes inclusion of the word ``pollination'' as an example
of a process leading to syngamy in the definition of conventional
breeding addresses this concern. Pollination, the transfer of pollen
from an anther to a stigma (Ref. 9), is the process through which
traditional breeding with most angiosperms, i.e., most major crop
plants, occurs (see e.g., 59 FR 60537) (Ref. 9). Inclusion of the word
``pollination'' in the definition emphasizes that plant-incorporated
protectants that occur naturally in a plant growing from a viable
zygote that arises by the mating in conventional breeding of one corn
variety with another, or the mating of a corn plant with a corn plant
of the same variety are exempt.
    EPA recognizes that this same concern of ambiguity also applies to
plant-incorporated protectants in plants that are propagated
vegetatively. EPA believes inclusion of the phrase ``vegetative
reproduction'' in the definition of conventional breeding addresses
this concern. The language of the exemption for plant-incorporated
protectants derived through conventional breeding from plants sexually
compatible with the recipient plant specifically exempts plant-
incorporated protectants in plants reproduced vegetatively. For
example, plant-incorporated protectants in a plant propagated only
vegetatively, (e.g., bananas), are exempt. Also exempt are plant-
incorporated protectants in a plant propagated primarily vegetatively
(e.g., potatoes), as long as, under conditions of reproduction through
hybridization, the plant donating the genetic material is sexually
compatible with the recipient plant as defined in at 40 CFR 174.3, and
the other conditions described at subpart B, in particular 40 CFR
174.25, are met. Inclusion of the term vegetative reproduction in the
definition of conventional breeding reflects EPA's statement in the
1994 proposed rule (59 FR 60524) on the status of crop plant varieties
propagated vegetatively.
    c. Will wide and bridging crosses be part of the definition of
conventional breeding? In this final rule, EPA is implementing a
definition of ``sexually compatible'' that includes wide and bridging
crosses. In this final rule, wide crosses means to facilitate the
formation of viable zygotes through the use of surgical alteration of
the plant pistil, bud pollination, mentor pollen, immunosuppressants,
in vitro fertilization, pre-pollination and post-pollination hormone
treatments, manipulation of chromosome numbers, embryo culture or ovary
and ovule cultures.

[[Page 37796]]

    Generations of artificial hybridizations through these techniques
have taken place in the well-established practices of plant breeding
(Ref. 7). Wide crosses have been in the past, and are currently,
commonly used to expand the plant gene pool for varietal improvement
(Ref. 7), and a history of safe use has been associated with plant
varieties developed through the use of wide cross techniques (Ref. 7).
A fairly high degree of relatedness between the parental plants is
indicated when a wide cross produces a viable zygote. This high degree
of relatedness indicates a low probability of new exposures.
    The definition of ``bridging crosses between plants'' is intended
to convey the concept that an intermediate plant could be used in a
cross to move traits from a source plant into a desired recipient
plant. The intermediate plant can form viable zygotes with both the
source and recipient plants, whereas the source and recipient plant
cannot form viable zygotes. The intermediate plant serves as a bridge
for gene flow between the two incompatible plants. The result of the
bridging cross is the mixing of genetic material of the first and third
plant through the formation of an intermediate zygote. No comments were
received on the proposed definition of bridging crosses between plants,
also part of the definition of conventional breeding for sexually
compatible. EPA is adopting this definition as proposed.
    d. Will cell or protoplast fusion be part of the definition of wide
crosses? EPA received one comment suggesting that protoplast fusion
should be included in the definition of wide crosses between plants. In
the technique of protoplast fusion, protoplasts are made in the
laboratory through the removal of the cell walls of somatic cells. A
somatic cell is a type of cell that forms plant vegetative tissues and
organs and is distinguished from a germ cell which undergoes meiosis to
produce reproductive tissues (e.g., pollen and egg cells). In the
technique of protoplast fusion, protoplasts are made from the somatic
tissue of two different plants. The membranes of the different
protoplasts are then fused together mechanically through processes such
as treatment with polyethylene glycol, producing a hybrid somatic cell
with a genetic make-up resulting from the combination and sorting of
the two plant genomes. The somatic hybrid cell is then grown on
specialized media into a mature plant.
    In support of the request, the commenter argued that the
hybridization of somatic cells has a history of use to artificially
induce sexual compatibility. The commenter argued that movement of
genetic material by this means has historically been considered safe.
    EPA did not, in its 1994 proposed rule include protoplast fusion in
the definition of wide crosses between plants, nor did it perform an
analysis of the potential for new exposures when protoplast fusion is
used to perform wide crosses between plants. The commenter did not
provide such information in response to the 1994 proposed rule nor the
1997 supplemental document. EPA does not believe information currently
in the record supports inclusion of protoplast fusion in the definition
of wide crosses. Therefore, EPA does not in this rule include
protoplast fusion in the definition of wide crosses, and specifically
excludes cell fusion from the definition of conventional breeding.
However, EPA requests comment on whether protoplast fusion should be
included in the definition of wide crosses in a supplemental document
published elsewhere in this issue of the Federal Register. EPA would
welcome submission of information on protoplast fusion. If the Agency
obtains sufficient information demonstrating a low probability of risk,
EPA may initiate notice-and-comment rulemaking under FIFRA section
25(b) and FFDCA section 408 to include protoplast fusion in the
definition of wide crosses between plants.
    e. ``Recombinant DNA'' and genetic material ``extracted from an
organism and introduced into the genome of the recipient plant.'' As
explained previously, EPA restricted this exemption to conventionally
bred plant-incorporated protectants while the Agency solicits
additional comment on the alternatives it is considering in response to
the comments received on the 1994 proposal. Thus, in order to fully
describe which plant-incorporated protectants are exempt under this
exemption, EPA includes limiting phases. EPA in the 1994 Federal
Register document (59 FR 60529) discussion of the advice of the SAP and
BSAC at the January 21, 1994 meeting on the use of a process-based
criterion to define a category of plant-incorporated protectants that
would be subject to review, stated that the Agency would define such a
process-based criterion in the following way: ``The genetic material
that encodes for the pesticidal substance or leads to the production of
the pesticidal substance is extracted from an organism and introduced
into the genome of the recipient plant or is synthesized in vitro and
introduced into the genome of the recipient plant.'' In this action,
EPA uses the language it put forth in the 1994 Federal Register
document (59 FR 60529) to fashion two of the exclusions from the
conventional breeding definition at 40 CFR 174.3. One exclusion is for
techniques involving genetic material that has been extracted from the
source and introduced into a recipient plant. Processes such as micro-
injection, macro-injection and micro-encapsulation would be excluded
from the conventional breeding exemption because they are used to
introduce such extracted genetic material into the recipient plant.
These processes have been included in the definition as examples to
assist in understanding the concept.
    The second exclusion from the conventional breeding exemption uses
the term ``recombinant DNA'' to represent the concept of ``extracted
from an organism. . ., synthesized in vitro and introduced into the
genome of the recipient plant.'' To provide greater technical accuracy,
EPA provides a definition at 40 CFR 174.3 for recombinant DNA as
follows:
    Recombinant DNA means the genetic material has been manipulated
in vitro through the use of restriction endonucleases and/or other
enzymes that aid in modifying genetic material, and subsequently
introduced into the genome of the plant.

    ii. Why is the concept of ``functionally modified from the source''
important and how does the definition of conventional breeding address
it? In the November 23,1994 Federal Register document (59 FR 60524),
EPA explained that in proposing the exemptions the Agency did not
intend to exempt a plant-incorporated protectant that is significantly
different in structure or function from a plant-incorporated protectant
as it occurs in the source. EPA believed this limitation was
appropriate because rearrangements or modifications of the genetic
sequence encoding a pesticidal substance made through the use of
techniques such as rDNA could, for example, result in a plant-
incorporated protectant with significantly different functions from the
functions in the source plant. For example, if the pesticidal substance
is an enzyme, it could be modified so that it acts on a different
substrate in the recipient plant than it did in the source plant (Refs.
7 and 16). Such a significantly modified plant-incorporated protectant
would not necessarily present risks similar to the substance prior to
modification, nor would the base of experience on which EPA relies for
support of the exemption necessarily be relevant. If the genetic
material encoding the pesticidal

[[Page 37797]]

substance has been modified in such a way that the pesticidal substance
functions differently in the recipient plant than it did in the source
plant, the analysis performed to determine that the plant-incorporated
protectant poses a low probability of risk to the environment and is
not likely to cause unreasonable adverse effects to the environment
even in the absence of regulatory oversight under FIFRA, would not
apply.
    In this final rule, this concern is addressed by the limitation
placed on the definition of sexually compatible. Under this definition,
plant-incorporated protectants derived from plants sexually compatible
with the recipient plant are only exempt if they are introduced into
the plant through conventional breeding as defined at 40 CFR 174.3. The
types of changes discussed above (Refs. 7 and 16) that can be made
through modern molecular techniques, are very unlikely to be made
through conventional breeding as defined at Sec. 174.3, and plant-
incorporated protectants modified through modern molecular techniques
are not eligible for this exemption.
    iii. Why is the phrase ''never derived from source not sexually
compatible with recipient plant'' important? EPA discussed the
relevance of this phrase to the exemption in the November 23, 1994
Federal Register document (59 FR 60523). The phrase, ``has never been
derived from a source that is not sexually compatible with the
recipient plant,'' which is part of the language of the exemption at 40
CFR 174.25, was meant to clearly indicate that a plant-incorporated
protectant would not qualify for the exemption if the genetic material
introduced into a recipient plant is from a sexually incompatible
source and then this recipient plant subsequently used to move the
introduced genetic material into plants sexually compatible with this
first recipient plant. For example, the exemption does not extend to a
situation where the genetic material encoding the Bacillus
thuringiensis delta endotoxin is introduced into wheat, and the
endotoxin-producing wheat is subsequently hybridized with rye using
wide cross techniques to produce triticale. The endotoxin produced in
the triticale would not be eligible for the exemption because the
genetic material encoding the endotoxin originated from a bacterium, a
source that is not sexually compatible with the original recipient
plant (wheat in this example).
    EPA received a comment that suggested that the Agency delete this
phrase from the regulatory text and instead include a period of time
after which a plant-incorporated protectant would be treated as part of
a plant's ``accessible'' gene pool. EPA does not accept the suggestion
to delete this phrase from the regulatory text, and continues to
include this language in the final rule at 40 CFR 174.25. EPA will not
implement the commenter's suggestion that a gene, derived from a
phylogenetically distant source and successfully used in a crop, be
treated after a period of time as though it had become part of the
crop's gene pool (i.e., equivalent to a gene that had evolved in a
sexually compatible population of plants). The commenter does not
suggest what an appropriate period of time would be, nor how this would
correlate with the potential for new exposures or low probability of
risk. Without additional information, it is difficult for EPA to make a
finding that there is a low probability of risk, or to assess the
likelihood of unreasonable adverse effects as required by FIFRA section
25(b).
    iv. What other general qualifications apply to exemptions and how
do these qualifications apply to plant-incorporated protectants derived
through conventional breeding from sexually compatible plants? EPA at
40 CFR 174.21 lists general qualifications that must be met in order to
qualify for an exemption from FIFRA requirements. These include
qualifications relating to plant-incorporated protectants intended to
be produced and used in a crop to be used as food, and to inert
ingredients.
    a. Plant-incorporated protectants in a crop used as food. As noted
in Unit II., the FQPA in 1996 modified the FIFRA definition of
``unreasonable adverse effects on the environment'' by adding a
criterion requiring consistency with the standard under FFDCA section
408 (Public Law 104-170 (August 3, 1996)). EPA includes at 40 CFR
174.21 a general qualification that clearly states this requirement in
the context of conditions necessary for the exemption of plant-
incorporated protectants.
    To understand how the status of a plant-incorporated protectant
under FFDCA affects the status of the plant-incorporated protectant
under FIFRA, the following must be considered: first, is the plant-
incorporated protectant in a crop used as food; second, are the
residues of the pesticidal substance and the residues of the genetic
material of that plant-incorporated protectant exempt from FFDCA
section 408?
    Is the plant-incorporated protectant in a crop used as food? In
order to exempt a plant-incorporated protectant from regulation under
FIFRA, EPA must determine that the plant-incorporated protectant poses
a low probability of risk, and will not cause unreasonable adverse
effects on the environment even in the absence of regulatory oversight.
How a plant-incorporated protectant can meet these standards differs
somewhat depending on whether or not residues of the plant-incorporated
protectant are in food. As noted in Unit II., as a practical matter a
plant-incorporated protectant in food cannot be exempted from FIFRA
requirements unless an exemption from the FFDCA section 408 requirement
of a tolerance has been issued for the residues of the plant-
incorporated protectant in food.
    If a plant-incorporated protectant is used in a crop used for food,
unless there will be no residues in the food, the FFDCA section 408
requirements must be considered when determining whether the plant-
incorporated protectant can be exempted from FIFRA requirements. To be
exempted from FIFRA requirements, exemptions from the FFDCA requirement
of a tolerance must exist for all of the residues of the plant-
incorporated protectant. In accordance with the statutory definition of
a ``pesticide chemical residue,'' EPA anticipates that in most cases
the residues of a plant-incorporated protectant will consist of the
pesticidal substance, the genetic material necessary to produce the
pesticidal substance, any substance that might function as an inert
ingredient as defined for plant-incorporated protectants (e.g.,
selectable marker), and the genetic material necessary for production
of the inert ingredient (21 U.S.C. 321(q)).
    If a plant-incorporated protectant is not used in a crop used for
food (e.g., the plant-incorporated protectant is produced and used in a
plant in a species used only for ornamental purposes), the FFDCA
section 408 requirements do not need to be considered when determining
whether the plant-incorporated protectant can be exempted from FIFRA
requirements.
    If the plant-incorporated protectant is used in a crop used as
food, are the residues of the pesticidal substance exempt from FFDCA
section 408? In a companion document published elsewhere in this issue
of the Federal Register, EPA exempts from the requirement of a
tolerance residues of the pesticidal substance portion of plant-
incorporated protectants produced through conventional breeding from
sexually compatible plants, and the residues of any substance used to
confirm or ensure the presence of the active ingredient. The basis for
this exemption is the determination that there is a reasonable
certainty that no

[[Page 37798]]

harm will result from aggregate exposure to these residues. Thus, the
answer to this question is yes for plant-incorporated protectants
derived through conventional breeding from sexually compatible plants,
with the limitation that the exemption does not apply when the residues
are present in food at levels that are injurious or deleterious to
human health. (For a detailed discussion of this limitation, see the
companion document published elsewhere in this issue of the Federal
Register.)
    If the plant-incorporated protectant is used in a crop used as
food, are the residues of nucleic acids that are part of a plant-
incorporated protectant exempt from FFDCA section 408? The answer to
this question is yes. In a companion document published elsewhere in
this issue of the Federal Register, EPA exempts from the requirement of
a tolerance residues of nucleic acids that are part of a plant-
incorporated protectant because there is a reasonable certainty that no
harm will result from aggregate exposure to these residues.
    What is the status under FIFRA of plant-incorporated protectants
derived through conventional breeding from sexually compatible plants
in light of FFDCA requirements? Because of actions EPA takes in this
document, and in two companion documents published elsewhere in this
issue of the Federal Register under FFDCA section 408, plant-
incorporated protectants derived through conventional breeding from
plants sexually compatible with the recipient plant are exempt, whether
or not they are in food, from all FIFRA requirements, except for the
reporting requirements at 40 CFR 174.71.
    b. Inert ingredients. EPA also includes at 40 CFR 174.21 a general
qualification that describes how inert ingredients relate to the
exemptions at 40 CFR part 174, subpart B.
    With regard to how this general qualification applies to the
exemption of plant-incorporated protectants derived through
conventional breeding from sexually compatible plants, the preamble
discussion in the 1994 Federal Register document (59 FR 60523) of the
rationale supporting the proposal to exempt these plant-incorporated
protectants extends to any substance that is derived from plants
sexually compatible with the recipient plant, including substances such
as a selectable marker, used to confirm or ensure the presence of the
active ingredient. EPA's analysis in Units VII.D.3. and VII.D.4.,
applies equally to all the substances that normally characterize a
population of sexually compatible plants, including inert ingredients,
as long as these are derived through conventional breeding from plants
sexually compatible with the recipient plant, and have never been
derived from a source that is not sexually compatible with the
recipient plant. An example of such an inert ingredient in sexually
compatible plant populations could be tightly linked traits such as
unusual leaf pigmentation always found with a pest resistance trait.
    EPA includes in this final rule language at 40 CFR part 174,
subpart X, to ensure that readers understand that any inert ingredient,
and the genetic material necessary to produce it, that occurs naturally
in a plant or is introduced through conventional breeding, is exempt
when used with a plant-incorporated protectant derived through
conventional breeding from a plant sexually compatible with the
recipient plant. EPA believes this interpretation is a logical
implication of the preamble discussion in the 1994 proposed rule (59 FR
60538).
    Because the Agency recognizes that a substance with potential for
adverse effects (i.e., a toxicant) could theoretically be used as a
selectable marker, or inert ingredient, EPA places the same limiting
condition on residues of the inert substance in food as is placed on
residues of the pesticidal substance portion of the active ingredient;
i.e., the residues of the substance portion of a selectable marker, or
inert ingredient, do not qualify for the exemption if they are present
in food from the plant at levels that are injurious or deleterious to
human health.
    Additional findings and conclusions supporting this exemption may
be found in the companion document published elsewhere in this issue of
theFederal Register 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.''
    The regulatory text of new 40 CFR 174.485, which is entitled
``Inert ingredients from sexually compatible plant,'' can be found in
the regulatory text of this document.
    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 subpart X 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. 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(e), 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. For more details on filing objections or
requesting hearings pursuant to regulations promulgated under the
FFDCA, see the discussion in the companion document published elsewhere
in this issue of the Federal Register (under ``Objections and Hearing
Requests'').
    v. What were the other potential approaches to scope of exemption?
In the November 23, 1994 Federal Register document (59 FR 60523), EPA
discussed the merits of two approaches using taxonomy, in whole (Option
2) or in part (Option 3), as a standard for describing closely related
plants, and received comment on use of such a criterion. EPA also
received a comment suggesting that the criterion of sequence homology
be used to limit the concept of sexual compatibility.
    a. Taxonomy. Two commenters expressed reservation about using a
taxonomic standard for describing closely related plants. They pointed
out that taxonomic categories, and the relationship of a given plant
species to a given taxon, may be transient since taxonomic
classification may change as information accrues. EPA noted in the
discussion of Option 2 and Option 3 in the 1994 Federal Register
document (59 FR 60524) that a taxonomy-based standard may be
artificial: classification of plants in different taxonomic genera is
not fixed and could change over time and between scientific
authorities. Taxonomy reflects current observations about phenotypic,
and to some extent, genotypic, differences between organisms.
Currently, some plant genera are narrowly defined; for other plant
genera, membership is based on broader criteria. These differences in
classification criteria may lead to different probabilities between
genera that new exposures may occur when genetic material from one
species in a genus is introduced into another species in the genus. In
recent years new tools have become available to taxonomists, allowing
them to better clarify phylogenetic relationships among organisms. New
information,

[[Page 37799]]

particularly that obtained through the use of new genetic tools,
concerning organisms' properties and relationships may in the future
alter current taxonomic designations. In light of these advances, EPA
anticipates there may be some reorganizations among the Plantae, and
that these reclassifications will better reflect the relationships
among plants, and the probability of new exposures in intrageneric
crosses.
    The possibility that taxonomic classification may change as
information accrues adds an extra layer of complexity to any
regulations based on a taxonomic standard, and EPA probably would not
be able to structure an exemption to accommodate for potential changes
in classification. The possibility of reclassification also creates
some uncertainty within the regulated community about the future status
of a product.
    In addition, taxonomy may be a more artificial standard than sexual
compatibility as a predictor of different environmental exposures of a
plant-incorporated protectant, particularly for unmanaged or semi-
managed plants. Isolation, adaptation to unique environments, and low
natural rates of gene flow characterize many natural populations. For
these types of plants, a taxonomic standard may not be as appropriate
as a standard based on sexual compatibility with regard to novel
exposures to plant-incorporated protectants. At the January 21, 1994,
joint meeting of the Subpanel of the SAP and the BSAC Subcommittee, the
scientific advisory groups questioned whether the reasoning supporting
use of a standard based on sexual compatibility supported equally well
a standard based on taxonomy for semi-managed plants (e.g., trees).
They indicated it probably did not for the reasons cited in this
paragraph (Ref. 15).
    b. Sequence homology. The suggested criterion of sequence homology
would base relatedness on the degree of sequence homology between the
source and recipient plant. Sequence homology refers to the extent that
the sequence of deoxynucleotides in two pieces of genetic material are
the same (Ref. 17). A deoxynucleotide is made up of a sugar, a
phosphate, and one of four purine or pyrimidine bases (adenine,
cytosine, guanine, thymine). The sugars and phosphates of the
deoxynucleotides are covalently linked by phosphodiester bonds to form
the ``backbone'' of the deoxynucleotide polymer (DNA). One base is
attached to each sugar in the sugar-phosphate backbone. The information
encoded in the genetic material is determined by the sequence in which
the bases are attached to the sugar-phosphate backbone. The extent to
which two pieces of genetic material have the same base sequence is
often described in terms of percent homology, with 100% homology
meaning the pieces of genetic material have an identical sequence. The
Agency believes that, in general, DNA sequence homology is a less
straight-forward standard for regulatory purposes than a standard such
as sexual compatibility. Sexual compatibility is known in most cases,
and if it is not, it is less burdensome and simpler to demonstrate than
is relatedness based on DNA sequence homology. Use of homology as a
criterion presents the following complex issues. First, where should
homology be assessed? For example, how many genes of the source and
recipient plants should be compared to determine the degree of
homology? All the genes of both plants? A few genes? If only a few,
which genes? Second, what degree of homology would be sufficient to
indicate a high degree of relatedness? Third, under what conditions
should homology be measured? Fourth, appropriate test procedures would
need to be developed and validated in order to set a standard procedure
for measuring homology. All of these issues would need to be resolved,
and converted into regulatory text, in order to develop an exemption
standard based on DNA sequence homology.
    2. How did EPA assess this category of plant-incorporated
protectants? Typically, in assessing a pesticide for environmental
risk, EPA uses the information requirements generated pursuant to 40
CFR part 158 to evaluate the potential effect of the pesticide on
birds, mammals, freshwater fish and invertebrates, estuarine and marine
animals, and nontarget plants and insects (e.g., predators, parasites
and honey bees). For most pesticides, this information is generated
using animal models. To address these same questions for the plant-
incorporated protectants that are the subject of this exemption, EPA
was able to rely on the large and varied information base available in
the public scientific literature.
    Generally, when EPA assesses the risks caused by the use of a
pesticide, it considers both the potential hazard that the pesticide
poses to the environment and the potential for exposure to the
pesticide due to its use. For most pesticides (e.g., chemical
pesticides), EPA's risk evaluation relies on data generated by testing
in laboratories using representative animal models to estimate risk
end-points. Other information, including product analysis data and
information generated by use of mathematical models, are used to
develop exposure estimates. Exposure and hazard estimates are combined
to quantify the potential risk associated with the pesticide's use. The
data requirements describing the types of information to be generated
and other guidance for assessing risk is detailed in 40 CFR part 158.
    The questions posed as part of the risk assessment in evaluating
most pesticides (e.g., chemical pesticides) can also be posed for the
plant-incorporated protectants that are exempted in today's action, and
40 CFR part 158 can be used as guidance. EPA adopted an approach for
evaluating the potential risks of plant-incorporated protectants
exempted by this final rule, that is consistent with the unique
characteristics of pesticides produced and used in a living plant, and
the scientific knowledge and experience accumulated on these
substances.
    To address the hazard endpoints described in 40 CFR part 158 for
the plant-incorporated protectants that are the subject of this
exemption, EPA relied on a very large body of information developed
through systematic scientific study that exists in the public
literature (Ref. 18). This literature was developed through many
decades of testing and observation. EPA thus could rely on this
information and did not need to rely only on animal model testing to
assess risk. EPA was also able to rely on information in the literature
in evaluating the potential for exposure to the plant-incorporated
protectants that are the subject of this exemption. Plant-incorporated
protectants are produced within the living plant and the pesticidal
substance is used in situ in the plant and this affects the exposure
paradigm.
    3. On what basis did EPA determine that plant-incorporated
protectants derived through conventional breeding from sexually
compatible plants present a low probability of risk? EPA considered
several factors in determining whether plant-incorporated protectants
derived through conventional breeding from sexually compatible plants
could be exempted from FIFRA requirements. These include: First, the
large body of knowledge that currently exists on plants in sexually
compatible populations derived through conventional breeding; second,
the potential for novel exposures; third, the potential for
quantitative changes in the levels of substances normally found in
plants in sexually compatible populations that might cause adverse
effects; and, fourth outcrossing of the

[[Page 37800]]

ability to produce these substances to wild or weedy relatives. To
support its conclusions that this category of plant-incorporated
protectants present a low probability of risk, EPA also relied on the
analyses laid out in the tolerance exemptions published elsewhere in
companion documents in this issue of the Federal Register. Rather than
reiterate all of these analyses here, EPA refers readers to the
detailed discussions in those documents. EPA believes that the
conclusions reached for plant-incorporated protectants derived through
conventional breeding from sexually compatible plants also apply for
other substances that might be considered part of the pesticide product
(e.g., inert ingredients) for these plant-incorporated protectants.
    i. Large body of knowledge and experience exists. In the issue
paper entitled ``FIFRA: Benefit and Environmental Risk Considerations
for Inherent Plant-Pesticides,'' (Ref. 18) EPA describes a large part
of the information base on nontarget plants, insects, birds, mammals
and other herbivores the Agency utilizes for its evaluation of the
potential effects of the plant-incorporated protectants that are the
subject of this exemption (Ref. 18). In addition, EPA uses the large
literature on the effect on humans of consumption of food from plants
in sexually compatible populations developed through conventional
breeding generated from epidemiological studies, nutritional
assessments, animal model testing and biochemical studies (Refs. 7, 8,
19, 20, 21, 22, 23, 24, 25, 26, and 27) to draw conclusions on the
potential risk for animal non-targets, including birds and fish, which
might consume food or feed containing plant-incorporated protectants
that are the subject of this exemption. Just as testing in animal
models can supply information that is extrapolated to conclusions on
the effect of a substance on humans, so too can information and
conclusions drawn in the dietary risk assessment on the effects on
humans be extrapolated to predict effects on non-human mammals and
other animals in an assessment of environmental risk. In addition,
there is a long history of hundreds, if not thousands of years, of
humans using foods containing the plant-incorporated protectants that
are the subject of this exemption as feed for domesticated and other
animals, including birds and fish (Ref. 28, for example). EPA relies on
these experiences and the large literature generated by a century of
systematic studies of the constituents of food (Refs. 7, 8, and 18) to
assess the plant-incorporated protectants that are the subject of this
exemption.
    EPA also took into account scientific knowledge from a number of
disciplines including plant genetics, plant physiology, phytopathology,
entomology, biochemistry, microbial ecology, ecology and plant
breeding. From these disciplines, EPA considered, for example,
information on plant metabolism, the production of substances that may
have a pesticidal effect, and conditions that may limit the production
of such substances (Refs. 9, 17, 18, 29, and 30). The Agency also used
experimental data derived from the science of phytopathology to
characterize the pest resistance mechanisms in plants (Ref. 29).
    ii. Low potential for novel exposures. Humans and the environment
are currently being, and have been for long periods of time, exposed to
plants containing the plant-incorporated protectants that are the
subject of this exemption. Based on the knowledge base described above
in Unit VII.D.2., current conditions of exposure pose a low probability
of risk.
    Sexually compatible plants share a common pool of genetic material,
even though there may be some variability among plants in sexually
compatible populations. Sexual compatibility, the ability to produce
viable offspring, is only possible in nature for organisms that possess
many traits in common. Traits, and the genetic material encoding them,
can be passed through a sexually compatible plant population by mating,
and the mixing of genetic material that occurs through mating tends to
a situation where the members of a sexually compatible population have
similar traits and similar genetic material. Thus, movement through
conventional breeding of genetic material encoding pesticidal
substances between plants in a sexually compatible population is
unlikely to result in exposure of organisms that associate with a plant
in that population to plant-incorporated protectants that they, and
their ancestors, had not been exposed to previously. If a population of
plants normally possesses a pesticidal substance, organisms that come
into contact with some plants in that population have likely been
exposed to that substance in the past, perhaps over long periods of
time. These past exposures, particularly if they occur over long
periods of time, may lead to a degree of adaptation, or tolerance, in
the population of organisms exposed to the pesticidal substance (Ref.
9). The potential for novel, or significantly different environmental
exposures to occur in such a situation, would be low.
    Further, the potential for exposure to plant-incorporated
protectants is in general lower than for other types of pesticides,
because plant-incorporated protectants are produced within the living
plant and used in situ in the plant. Most other pesticides must be
applied to the plant, or near the plant. Because a plant-incorporated
protectant is produced and used within the plant, physiological
constraints limit the amount of pesticidal substance produced by the
plant. Because the plant-incorporated protectant is within the plant,
the 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. Because plant-
incorporated protectants are produced and used in the living plant,
actual physical contact with the plant or plant parts will, in general,
be necessary for exposure to occur. In addition, the plant-incorporated
protectants exempted by this final rule are part of the metabolic
cycles of plants. They, thus, are biotic and are subject to the
processes of biodegradation and decay that all biotic materials undergo
(Ref. 31). Biotic materials are broken down to constituent parts
through the enzymatic processes of living organisms, and these
constituent parts used as building blocks to make other biotic
substances. Furthermore, the plant-incorporated protectants that are
exempted in this action are biodegradable to their constituent elements
through catabolism by living organisms. Because of their biodegradable
nature, these plant-incorporated protectants 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 (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) in the tissues of living organisms
as do substances, such as dioxin (Ref. 32). Because of these
characteristics, the potential for new exposures to occur, beyond
direct physical exposures to the plant or plant parts, is limited for
plant-incorporated protectants derived through conventional breeding
from sexually compatible plants.
    EPA received a comment raising the concern that ``wild-type or

[[Page 37801]]

conventionally bred plants in new environments attract, repel or
otherwise influence biota surrounding them.'' In response, EPA would
first point out that as described in Unit VII.B.5., a key statutory
element in the FIFRA definition of pesticide is whether a human
``intends'' that a substance or mixture of substances be used for
destroying, preventing, repelling or mitigating a pest. A plant
introduced into the United States with reference only to its ornamental
beauty or its food value, without regard to ability to resist pests,
does not contain substance(s) meeting the FIFRA section 2(u) definition
of pesticide until a human intends the substance(s) be used for
preventing, destroying, repelling or mitigating a pest. Substances
within a plant introduced into the United States with pesticidal claims
are pesticides within the FIFRA section 2(u) definition. However, as
pointed out by the commenter, these substances would be exempt from
FIFRA requirements if derived through conventional breeding from
sexually compatible plants even though they present a potential for
novel environmental exposure. EPA believes this is appropriate. When
EPA proposed to exempt plant-incorporated protectants derived from
sexually compatible plants from FIFRA requirements, EPA recognized that
most crop plants, including all major crop plants, were not native to
the United States. The risk assessment the Agency performed and its
analysis of risks versus benefits as prescribed by FIFRA, led it to
propose the exemption based on a determination that the benefits of use
of agricultural crops already in the United States outweigh the low
probability of risk. The Agency also anticipated that the probability
that nonindigenous plants representing wide-spread exposure being
commercially introduced into the United States with pesticidal claims
in the future was low (Ref. 7). EPA also considered that the adverse
effects reporting requirement it was placing on the exemption would
serve to alert the Agency should any environmental or human health risk
be identified with such plants. In addition, EPA considered whether new
dietary exposures could occur with such plants. EPA concluded that for
any such plant introduced into the United States for food use, there
will likely be in the country of origin, a history of experience with
the dietary use of the plant or parts of the plant, even if a similar
history does not exist in the United States at the time of the
introduction. In performing its analysis of dietary risk, EPA found no
basis for assuming that the dietary effects of any plant-incorporated
protectant residues in such a food from such a plant would differ for
the United States population from that of the source country. Moreover,
EPA believes that the limitation in the tolerance exemption for
residues of the pesticidal substance portion of plant-incorporated
protectants derived through conventional breeding from plants sexually
compatible with the recipient plant will allow EPA and FDA to act
expeditiously should any substances meeting the FIFRA section 2
definition of pesticide be identified as problematic.
    iii. Low potential for significant increases in levels of plant-
incorporated protectants. EPA has evaluated whether there are likely to
be quantitative changes in levels of plant-incorporated protectants
derived through conventional breeding from sexually compatible plants,
such that adverse effects on the environment might occur. EPA has
determined that the probability of such an event is low because the
highest levels of pesticidal substances likely to be attained with
plant-incorporated protectants in this group are not likely to result
overall in significantly different environmental exposure levels. This
analysis was presented in an EPA issue paper, entitled: ``Benefit and
Environmental Risk Considerations for Inherent Plant-Pesticides'' (Ref.
18) located in the record for this rule as described in Unit VIII. A
summary of the analysis is presented here.
    EPA first considered whether an increase in the levels of
substances, including plant-incorporated protectants, that plants
normally produce is likely to exceed the ranges normally found within
and between plant varieties and uncultivated plants. The level of
production of such substances normally varies among sexually compatible
plants because of differences in potential to express a substance and
environmental conditions. Indeed, variation is seen even among plants
in the same variety because of differences such as weather and soil
condition. For example, one report (Ref. 7) has shown an 8.3-fold
variation in the amount of ascorbic acid in turnip greens depending on
the degree of exposure to light. Such variation could also characterize
natural variation in the levels of a plant-incorporated protectant and
variation in exposure for organisms that associate with the plant.
Nontarget organisms, such as birds and insect pollinators, that
associate with plants have been, and are currently being exposed to the
range of levels of plant-incorporated protectants being expressed by
plants within sexually compatible populations. This exemption will not
affect these exposure patterns.
    EPA also considered the extent to which any substance can be
increased in highly managed plants without unwanted effects on other,
desirable characteristics of the plant such as yield or palatability of
fruit. In general, breeders balance all of these characteristics in
developing marketable plant varieties. Plants have, as do all
organisms, only a limited capacity to express a particular trait
without a drain on energy reserves. Greatly increased levels of a
plant-incorporated protectant would, in general, only be accomplished
at the expense of the expression of other, agriculturally desirable
traits (Ref. 18).
    EPA anticipates that for the majority of agricultural plants,
levels of expression of substances such as plant-incorporated
protectants will continue to fall within currently observed ranges of
expression; EPA does not anticipate that variations in the level of a
plant-incorporated protectant that is normally a component of a plant
and derived through conventional breeding from plants sexually
compatible with the recipient plant would lead to a significantly
different spectrum of exposure to a plant-incorporated protectant.
Moreover, EPA believes that the history of familiarity with
agricultural plants in sexually compatible populations, and thus with
the likely progeny of genetic exchanges between plants in such
populations, and the procedures currently employed in plant breeding to
screen out undesirable traits also support this conclusion.
    Comments on quantitative changes and on the potential for plants
consumed in toto or in part as food to produce injurious or deleterious
effects have, however, caused EPA to reconsider its approach under
FFDCA to pesticidal substances derived through conventional breeding
from sexually compatible plants. To address concerns raised in comment
on the possibility that certain substances normally present in plants
in sexually compatible populations may in rare circumstances be present
in food at levels that are hazardous, EPA places a condition on the
exemption under FFDCA section 408 for pesticidal substances derived
through conventional breeding from sexually compatible plants.
Eligibility for exemption is based on the condition that the residues
of the pesticidal substance not be present in food from the plant at
levels that are injurious or

[[Page 37802]]

deleterious to human health. If the residues of the plant-incorporated
protectant do not meet this criterion, they are not exempt from the
requirement of a tolerance. Because the residues would not qualify for
the exemption and no tolerance would have been established, any food
containing such residues would be ``adulterated'' pursuant to section
402(a)(2)(A) of the FFDCA and subject to seizure (21 U.S.C. 342
(a)(2)(A)). As noted in Unit II., the status of a plant-incorporated
protectant under FFDCA can affect its status under FIFRA.
    EPA also considered issues of variation in levels of plant-
incorporated protectants and exposure of nontarget organisms to such
plant-incorporated protectants for plants in semi-managed systems
(e.g., trees) (Ref. 18). EPA anticipates that for such plants, levels
of expression of substances such as plant-incorporated protectants will
continue to fall within currently observed ranges of expression. EPA
does not anticipate that variations in the level of a plant-
incorporated protectant in these plants would lead to a significantly
different spectrum of exposure to a plant-incorporated protectant. It
is not anticipated that the levels of plant-incorporated protectants in
these plants would significantly exceed existing expression ranges of
their free-living relatives (Ref. 18).
    One commenter worried that because levels of substances in plants
vary in response to environmental conditions, the legal status of a
plant-incorporated protectant could change from exempt to non-exempt as
the levels of pesticidal substances fluctuate. While it is possible,
particularly in light of the condition placed on the exemption from the
requirement of tolerance, that the legal status of a plant-incorporated
protectant could change from exempt to non-exempt, EPA anticipates this
will occur only very rarely, if at all. In its assessment, EPA
considered the probability of variations in levels of plant-
incorporated protectants derived through conventional breeding from
sexually compatible plants presenting risk. EPA concluded that although
variations will occur in response to environmental conditions, in the
range of levels likely to occur they pose a low probability of risk
from quantitatively different exposures. EPA's conclusion that it is
unlikely that variation due to environmental conditions, or to breeding
decisions, would result in risk from quantitatively different exposures
is reflected in the Agency's reliance on the post marketing monitoring
afforded by the adverse effects reporting requirement at 40 CFR 174.71.
    iv. Low potential for weediness from outcrossing from plants
derived through conventional breeding to wild relatives. A question
directly affecting the exposure component of the risk assessment that
has no equivalent in the assessment of more traditional pesticides
(e.g., chemical pesticides) must be posed for plant-incorporated
protectants. Because plant-incorporated protectants are produced and
used in the living plant, the possibility that the ability to produce a
plant-incorporated protectant may be transferred by outcrossing and
hybridization from the crop plant to a cultivated, wild or weedy
relative was considered for the plant-incorporated protectants exempted
in this action. A large volume of information is available in the
public literature (Ref. 33) on this possibility for plant-incorporated
protectants derived through conventional breeding from sexually
compatible plants. EPA's issue paper entitled ``Risk Considerations for
Outcrossing and Hybridization'' describes in part the information base
used to address this aspect of the assessment (Ref. 33).
    One of the considerations evaluated for this exemption was whether
a capacity to express higher levels of pesticidal substances could be
transmitted to wild relatives through outcrossing of the genetic
material necessary for the production of the pesticidal substance. A
second and more important consideration is whether such an outcrossing
event, could in turn, increase weediness of the wild relative. EPA
believes that the potential for weediness to increase in wild relatives
through the transfer of the genetic material for the pesticidal
substance from a crop plant is low for the following reasons.
    First, there are several factors which govern whether gene flow
occurs between crops and their wild relatives (Ref. 34). Genetic
barriers can prevent hybrids from forming, render them sterile, or
reduce the fertility of hybrids, and, thus, restrict their contribution
to subsequent generations. The strength of genetic barriers is
correlated to degree of evolutionary relatedness between the crop and
wild relatives (Ref. 34). Space is an effective barrier to
hybridization. The wild relatives of corn with which it can hybridize,
are restricted to Mexico and Central America. There is no danger of
hybridization in other regions (Ref. 34). Time of flowering can prevent
hybridization when there is no overlap in the time of flowering of
cultivated and wild forms (Ref. 34). The breeding system of the crop
plays an important role. For some species (e.g., peanut), the flowers
do not ordinarily open, and self-pollination may be very near 100%
(Ref. 34). The ploidy level may differ between a crop and its
relatives, and differences in ploidy levels can severely reduce the
likelihood that the cultivated plant and wild relative will form
fertile hybrids (Ref. 34). Some varieties of certain crop species, such
as banana, are sterile, and thus are incapable of hybridizing not only
with members of other species, but also of their own species (Ref. 34).
For some crops in the United States, the probability of gene transfer
and hybridization with the wild relative is zero, while for other
crops, despite the variety of potential barriers to and selection
against hybridization, it is possible.
    Second, in general, wild members of sexually compatible populations
tend to already possess higher levels of resistance to pests and
disease than do the cultivated members of those populations (Ref. 18).
Wild members of sexually compatible plant populations also tend to
express a greater range of levels of inherent plant defense compounds
than do cultivated plants, including production of higher levels of
substances that could potentially be used as plant-incorporated
protectants (Ref. 18). Indeed, during the past 100 years, it has been
common practice to cross crop plants with sexually compatible wild
relatives, since these wild relatives usually have higher levels of
resistance to a pest, in order to develop crop varieties with improved
resistance to the pest. For example, wild species of tomatoes have been
used, in conventional plant breeding, as a source of increased
resistance to economically important diseases in tomato (Ref. 7).
    EPA anticipates that for the majority of agricultural and semi-
managed plants, levels of expression of substances such as plant-
incorporated protectants, within plants in sexually compatible
populations, will continue to fall within currently observed ranges of
expression. EPA does not anticipate that variations in the levels of
substances such as plant-incorporated protectants, that are normally
components of a plant would lead to a significantly different range of
expression as a result of this exemption (Ref. 18). Thus, even should a
crop plant containing a plant-incorporated protectant in this exempt
category hybridize with a wild relative, it is unlikely that the range
of expression of the plant-incorporated protectant by the wild relative
will be substantially increased by acquisition of the trait from the
crop plant.
    4. On what basis did EPA determine that these plant-incorporated
protectants are not likely to present

[[Page 37803]]

unreasonable adverse effects to the environment even in the absence of
oversight? As explained in Unit II., a pesticide chemical meets the
standard for a FIFRA 25(b) exemption if the risks resulting from use of
that pesticide are consistent with the FFDCA section 408 exemption
standard, and the potential benefits of use outweigh any human health
or environmental risks even in the absence of regulatory oversight. EPA
considered several factors in determining whether the exempted plant-
incorporated protectants are not likely to cause an unreasonable
adverse effects to the environment. These include consideration of the
potential for dietary, both non-occupational and occupational human
health risks, and environmental risks. Also considered was whether the
language of the exemption clearly describes for the regulated community
what plant-incorporated protectants are exempt; how the scope of the
exemption under FIFRA relates to a companion exemption from the FFDCA
requirement of a tolerance for residues of these plant-incorporated
protectants; and general benefits to society, growers, consumers and
the environment.
    Some of these considerations were analyzed in detail in the
tolerance exemptions published elsewhere in companion documents in this
issue of the Federal Register. Rather than reiterate the analyses here,
the Agency has, in this section, limited its discussion of the human
health risks addressed in great detail in those documents to the
remaining risks for which the probability is so low that,
notwithstanding their existance, the residues meet the section 408(c)
standard. The standard for granting an exemption under section 408(c)
requires a ``reasonable certainty of no harm,'' not absolute certainty.
EPA can make the safety finding required under FFDCA section 408(c)
based on an extremely low probability or risks; a demonstration of ``no
risk'' is not required.
    i. Dietary risk considerations. EPA has determined that there is a
reasonable certainty that no harm will result from aggregate exposure
to residues of the plant-incorporated protectants that are the subject
of this exemption. For a full explanation of the factual bases for this
determination, readers are referred to EPA's assessment of human
dietary risks in the tolerance exemptions published elsewhere in
companion documents in this Federal Register, and to related documents
in the record for the rule as described at Unit VIII.
    In addition, the Agency evaluated the remaining dietary risks that
pose a negligible probability of causing adverse effects. As explained
throughout this preamble, and in associated rules, EPA believes that
the likelihood of dietary risks associated with the residues of plant-
incorporated protectants that are the subject of this exemption are
extremely low. However, it is possible that, notwithstanding the best
efforts of plant breeders, a toxicant could enter the food supply at
levels that could cause adverse effects. Because of the conditions of
the exemption, such food would no longer qualify for the exemption, and
would be subject to seizure. Thus, the extent of the harm is
anticipated to be extremely low.
    ii. Occupational and non-occupational risk to humans. Plant-
incorporated protectants are likely to present a limited exposure to
humans. In most cases, the predominant, if not the only, exposure route
will be dietary. Significant respiratory and dermal exposures are
unlikely because the substances are in the plant tissue and thus are
found either within the plant or in close proximity to the plant.
Although a potential for non-dietary exposure (e.g., dermal and
inhalation) in occupational settings may exist, EPA expects such
exposure to be negligible and thus human health risks to be negligible.
    a. Dermal exposure. Plant-incorporated protectants derived through
conventional breeding from sexually compatible plants may in some cases
be present in sap or other exudates from the plant or the produce 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. Farmers and food handlers (e.g.,
individuals harvesting produce by hand, preparing food for sale, or
stocking produce bins in grocery stores) or floral workers, are those
most likely to experience dermal contact with the substances on an
occupational basis. Although contact dermatitis is fairly common in
such workers (Refs. 35 and 36), these dermal reactions are generally
mild, of a self-limiting nature or self-diagnosed, and treated.
    Most of the substances that could be the subject of this exemption
are unlikely to pass through the skin to affect other organ systems
(Refs. 36 and 37). For those substances which possess to some degree
properties that allow some penetration of the skin, the potential
amounts passing through the upper layer of the skin (epidermis) are
negligible or the substances do not present adverse effects (Ref. 36).
    A group of substances that might be plant-incorporated protectants,
if humans intend to use them as pesticides, with the ability to present
an effect on dermal exposure in the occupational setting beyond a mild
contact dermatitis are the psoralens. These substances occur naturally
in a wide range of plants but occur in the highest concentrations in
celery, dill and parsley (Refs. 8 and 36). Psoralens can be phototoxic
to the skin in conjunction with sunlight (UV light). Due to their
relative solubility in oils, psoralens can penetrate into the skin
cells, where they intercalate into the genetic material of the skin
cell (Ref. 8). Subsequent exposure to sunlight (UV light) causes the
genetic material to ``cross link'', affecting the ability of the cell
to further process its genetic material. This may result in skin
blisters and rashes. This UV-dependent phototoxicity has also been
implicated in mutations that may lead to skin cancer (Ref. 8). In spite
of the potential for this type of adverse effect with the psoralens,
there are few reported incidents of this type of problem for substances
derived through conventional breeding from sexually compatible plants.
There is one reported incident in the 1980's where a celery variety
with high levels of psoralen caused rashes and dermatitis in produce
handlers (Ref. 7). The problem was identified and the variety removed
from the market.
    b. Inhalation exposure. Plant-incorporated protectants derived
through conventional breeding from sexually compatible plants may in
some cases be present in pollen and some individuals (e.g., those
working on farms in nurseries or other plant-growing areas) may be
exposed, through inhalation, to wind-blown pollen. When present in
pollen, the pesticidal substance is likely to 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. 36 and 38).
This exemption will not change current exposures nor affect strategies
for dealing with plant-incorporated protectants that are the subject of
the exemption (Refs. 36 and 38).
    iii. Environmental considerations. EPA examined, in Unit VII.D.3.,
the potential for environmental effects from the plant-incorporated
protectants that are exempted by this action. The Agency has determined
on the basis of its analysis that the probability of novel exposures to
nontarget organisms and to the surrounding ecosystems are low. EPA's
analyses indicate that the risks of outcrossing with wild relatives are
also anticipated to be low. Similarly, EPA's

[[Page 37804]]

analyses indicate that the risks of groundwater, or surface water,
contamination from these products are extremely low. EPA has thus
concluded that potential risks of environmental effects are not
significant.
    iv. Exemption criteria provide high degree of regulatory clarity.
EPA believes that using sexual compatibility coupled with the process
by which the plant-incorporated protectant is introduced into a plant
as a standard affords the most clear description of whether a plant-
incorporated protectant is exempt. Most plants have some form of sexual
reproduction characterized by the formation of gametes from haploid
germ cells, although some do not (Ref. 9). The definition of
conventional breeding at 40 CFR 174.3 provides for this latter category
of plants, which reproduce vegetatively. Plants reproduce either by
sexual processes or vegetative reproduction, and the limitations posed
by these natural barriers limits the transfer of genetic material to
plants within a sexually compatible population. These barriers can also
be effectively used to establish scope within regulations for plants.
    In most cases, whether two plants are sexually compatible is known;
thus, testing to determine whether the plants are sexually compatible
is not likely to be necessary. If, in some cases, it is not known
whether two plants are sexually compatible, the means of determining
sexual compatibility is straightforward and simple. Sexual
compatibility is empirically demonstrable. EPA believes that a standard
based on sexual compatibility provides a high level of regulatory
clarity and great ease of implementation. This standard allows the
public, industry, and EPA to easily and readily identify those plant-
incorporated protectants that are exempt.
    v. Exemption criteria create similar scopes under FIFRA and FFDCA
section 408. When EPA proposed its exemptions in 1994, one of its goals
was to create as similar a scope of exemption under FIFRA and the
section of FFDCA dealing with pesticides as possible, given the
differences in mandate and structure of the two statutes. EPA believed
that because it utilized the two authorities in concert to regulate
pesticides, similar exemptions under the two statutes would be
desirable. Such an approach would be simpler for the regulated
community to understand and for EPA to administer.
    In considering dietary risk under FFDCA section 408, EPA concluded
that a standard based on sexual compatibility exempts those plant-
incorporated protectants for which there is a reasonable certainty that
no harm will result from aggregate exposure. EPA, in a companion
document published elsewhere in this issue of the Federal Register,
exempts from the FFDCA section 408 requirement of a tolerance, residues
of pesticidal substances derived through conventional breeding from
sexually compatible plants. The information supporting that exemption
was generated on food from plants in sexually compatible populations
developed through conventional breeding.
    vi. No undue burden. The standard provided by criteria based on
sexual compatibility creates a similar exemption under FFDCA and FIFRA,
while at the same time implementing the standard with a high degree of
regulatory clarity. Implementing a standard with a high degree of
regulatory clarity that also creates similar exemptions under FFDCA and
FIFRA results in less burden on producers. In addition, EPA believes
that implementation of the exemption described in this document, and
the exemptions under FFDCA section 408 published elsewhere in companion
documents in this issue of the Federal Register, and the clarification
that plants used as biological control agents are exempt from FIFRA
requirements, minimize the burden of producers/developers while
appropriately addressing risk.
    One comment questioned the cost of EPA's proposed exemptions (59 FR
60519), appearing to believe that research scientists and industry
would have to notify and consult with EPA in order to qualify for
exemption. This final rule does not require producers to notify or
consult with EPA, or present data to the Agency in order to qualify for
exemption. The producer would determine whether a particular plant-
incorporated protectant meets the exemption criteria. EPA expects that
a producer will not have to create additional information specifically
to determine if a product is exempt, because producers will already
have such information from the ordinary course of product development.
There is no requirement to notify EPA associated with the exemption,
and no costs can be ascribed to such a notification process.
    Some comments offered general observations that costs would curb
the development of crop varieties. EPA believes that the clarification
that it will not regulate plants per se, and the exemptions it is
publishing in this document and in companion documents in this issue of
the Federal Register, limit EPA's effect on plant breeding and allow
most aspects of plant breeding to be pursued without EPA regulation.
    Some comments suggested that costs would inhibit the development of
alternatives to chemical pesticides. EPA has been, and continues to be,
committed to the development of safer pesticides, many of which are
biological pesticides, as possible alternatives to more toxic
pesticides. The Agency believes the actions it takes with regard to
plant-incorporated protectants encourage public confidence in the
safety of plants and foods from plants, developed using traditional and
modern techniques of biotechnology. The Agency believes that consumer
acceptance is key to the success of agricultural products, and that
consumer acceptance is strongly influenced by confidence that
regulatory agencies have ensured the public safety.
    vii. Benefits. The benefits to society associated with exemption
from FIFRA requirements of this category of plant-incorporated
protectants include general benefits to society from the practices of
horticulture and of agriculture in producing the food supply and other
plant based products (e.g., fiber, lumber), and economic benefits to
growers, and the environment.
    a. General benefits to society. Agriculture based on conventional
breeding allows much of the current world population of 6 billion
humans to feed itself. Development of higher yielding varieties through
conventional breeding in sexually compatible crop plant populations has
been an important means of feeding a growing human population (Refs. 39
and 40). For example, it has been estimated that the development of new
varieties of plants in sexually compatible populations through
conventional breeding accounts for about 80% of the increase in corn
yields from 1930 to 1980 and more than half of the increase in soybean
yields since 1920 (Refs. 41, 42, and 43). Similarly, genetic
improvements of plants in sexually compatible populations through
conventional breeding have been estimated to account for half the
increase in wheat yields from 1954 to 1979, almost two-fifths of the
increase in sorghum yields from 1950 to 1980 (Refs. 44, 45, and 46).
This exemption of plant-incorporated protectants derived through
conventional breeding from sexually compatible plants will allow the
type of genetic modifications leading to these types of yield gains to
continue with very minimal regulatory requirements.
    b. Growers. Growers who use plant-incorporated protectants derived
through conventional breeding from sexually compatible plants should be

[[Page 37805]]

able to maintain or increase their productivity. Use of these plant-
incorporated protectants could translate into lower grower costs
because growers will use fewer inputs. Growers should be able to reduce
the amount and type of chemical pesticides applied to a crop. Chemical
costs, energy costs (e.g., use of tractor) and labor expenditures will
be lower if the number of chemical pesticide applications decrease
(Refs. 47, 48, and 49). This category of plant-incorporated protectants
may also offer economic benefits to growers in circumstances where
traditional pesticides may not be as effective. For example, because
plant-incorporated protectants are produced and used in plants, they
may be more useful for combating pests that act systemically (e.g.,
stalk borers) than are some traditional pesticides sprayed on the
plant.
    c. Consumers. Lower food prices for consumers are anticipated
through use of plant-incorporated protectants derived through
conventional breeding from sexually compatible plants, because the use
of these plant-incorporated protectants may contribute to, or help
maintain, yield increases. If yields increase, the supply of food
should also increase. Consumer purchasing power could potentially
increase with the decrease in food prices.
    d. Environment. Environmental benefits associated with the use of
plant-incorporated protectants derived through conventional breeding
from sexually compatible plants include reduction in the use of
chemical pesticides. These chemical pesticides may not be
environmentally benign (Refs. 47, 48, and 49). Assuming that growers
reduce the number and type of chemical pesticide applications, field
workers would have reduced exposure. Other problems associated with
chemical pesticide use such as spray drift to other crops or plants,
exposure of nontarget species, groundwater contamination and spills
could also be reduced.
    In addition, breeding programs that develop varieties with, for
example, increased yield, better resistance to pests, and better
nutritional quality, could be part of an approach to agriculture that
would decrease some of the impacts of agriculture on the environment
while continuing to supply food to the growing human population. For
example, breeding programs that increase crop yields could reduce some
of the future impacts of agriculture by decreasing the amount of
additional land that would have to be brought into agricultural
production to feed the growing human population. The exemption
described in this document would allow breeding activities among plants
in sexually compatible populations through conventional breeding to
continue while imposing minimal burden.
    Finally, by exempting those plant-incorporated protectants unlikely
to result in novel exposures, EPA is concentrating its regulatory
efforts on those plant-incorporated protectants about which less
certainty exists with regard to the risk that would result from the use
of the plant-incorporated protectant. EPA would, for example, focus its
efforts on plant-incorporated protectants such as the toxin from a
spider. This toxin is targeted for the insect prey of the spider mite.
Plants are not known to produce this toxin in nature or in cultivation.
If this toxin were to enter the gene pool of a plant, organisms that
associate with the plant and that had never previously been exposed to
the toxin could now be exposed. Prior to the introduction of the toxin
into these plants, only the insect prey of the spider would potentially
be exposed to the toxin. If plants could now express the toxin, a
different or larger group of organisms could be exposed to it, possibly
resulting in adverse effects to these organisms. For example, if the
toxin is found in pollen, pollinators could be exposed to the toxin. By
concentrating its regulatory efforts in this way, EPA more efficiently
uses its own resources.
    viii. Reporting of adverse effects for exempted plant-incorporated
protectants. EPA has decided to adopt its proposed reporting
requirement for otherwise exempt plant-incorporated protectants. Under
40 CFR 174.71, anyone who produced an otherwise exempt plant-
incorporated protectant will be required to report any adverse effects
associated with the testing or use of the exempted plant-incorporated
protectant. Failure to comply with 40 CFR 174.71 would be an unlawful
act under FIFRA section 12(a) and could result in monetary penalties
pursuant to FIFRA section 14.
    As discussed throughout this preamble, EPA's analysis of the
potential risks has led it to conclude that the plant-incorporated
protectants that are the subject of this exemption present a low
probability of risk. But the Agency cannot rule out completely the
possibility of adverse effects to human health or the environment from
the testing and use of this large category of exempted plant-
incorporated protectants. The Agency cannot foresee all potential
adverse effects to human health and the environment that may
potentially arise for testing and use of specific plant-incorporated
protectants. This is compounded by the fact that the exemption is
broad, covering literally thousands of potential substances, some of
which have the potential to be toxic (Ref. 8, for example). The
reporting requirement is meant to address such unforeseeable events
resulting from the use of these pesticides.
    After weighing the remaining low probability of potential risks
against the potential benefits of the plant-incorporated protectants
within this category, EPA determined that the risks outweighed the
benefits in the complete absence of regulatory oversight. Even though
the potential benefits are very high, and the likelihood of risks are
estimated to be low, the nature of the potential hazard, a toxicant(s)
in the food supply, is extremely significant. Moreover, these products
present issues not seen with traditional pesticides: the potential for
spread of the plant's genetic material. Because plants can reproduce
sexually and/or asexually, the ability to produce the plant-
incorporated protectant could spread through the agro- or natural
ecosystems, particularly if wild relatives acquire the ability to
produce the plant-incorporated protectant through successful
hybridization. In addition, the extremely large category of substances
that will be exempt itself adds some degree of uncertainty to the
Agency's finding. EPA continues to believe that such risks are likely
to be extremely rare. However, these considerations would outweigh even
the benefits of the plant-incorporated protectants that are the subject
of this exemption in the absence of regulatory oversight.
    However, as discussed in Unit VII.D.5., EPA does not believe that
these risks justify requiring these products to be subject to the full
degree of regulatory oversight under FIFRA. Rather, taking into account
the very low probability of the risks, EPA believes that the post-
market requirement to report adverse effects, when taken with the
condition of the FFDCA exemption limiting the level of toxicants,
represents a sufficient degree of oversight to allow the Agency to
determine that the benefits outweigh the risks. The reporting
requirement at 40 CFR 174.71 is a means of ensuring that EPA and FDA
can address any potential hazard, and that the Agency's data base with
respect to such products is as complete as possible. The costs of
reporting are low for the regulated community, being calculated at
$669.00 per notification, with EPA anticipating three adverse effects
reports in 20 years,

[[Page 37806]]

but, as noted in the preceding paragraph, among other benefits, it will
provide a mechanism that will allow EPA and FDA to react quickly to
address the hazard, in the unlikely event it should arise. (See the
Economic Assessment for this rule (Ref. 50)). Therefore, to ensure that
there will be no unreasonable adverse effects on the environment from
the plant-incorporated protectants that are the subject of this
exemption, EPA is including in this final rule the reporting
requirement codified at 40 CFR 174.71.
    a. Comments on the reporting requirement. The majority of comments
supported the Agency's proposal. Two of these comments noted that
traditionally bred plants are monitored, both formally and informally,
for desirable properties, as well as for pests and disease, and
suggested that the Agency include a ``sunset clause'' in the
requirement.
    One comment disagreed with the adverse effects reporting
requirement and pointed out that the language of the proposed rule has
the potential of bringing in numerous reports of effects that are not
due to the plant-incorporated protectant.
    EPA carefully examined the comments it received on the proposed
adverse effects reporting requirement, including comments received from
other Federal agencies during the review process for this rule. In
establishing this reporting requirement EPA took into account the need
to target the requirement so that to the extent possible the Agency
would not receive numerous reports of effects that are not due to the
plant-incorporated protectant. On the other hand, guidance on what to
report that is too specific would be counterproductive given that the
purpose of the requirement is to be able to monitor for unforeseen
events. EPA balanced all of these considerations in developing its
final adverse effects reporting requirement at 40 CFR 174.71.
    EPA will not adopt a ``sunset clause'' for this requirement, i.e.,
a clause that would designate a period of time after which information
regarding adverse effects would no longer need to be reported to EPA.
EPA appreciates that plant breeders monitor for properties such as
yield, nutrients and resistance to pests. However, EPA does not have
adequate information on which to base such a clause. The commenters do
not define the parameters of the suggested ``sunset clause.'' In
addition, records would probably have to be kept to know when reports
would no longer be required for a particular plant-incorporated
protectant, adding an additional level of complexity to the
requirement. Finally, EPA believes that adverse effects reporting for
otherwise exempt plant-incorporated protectants should be the
responsibility of persons who produce plant-incorporated protectants
for sale or distribution. Plant breeders are not necessarily involved
in sale and distribution activities, and thus their access to
information that an adverse effect may have occurred may be limited.
    With regard to the concern expressed with respect to over-
reporting, EPA recognizes that the proposed regulatory text (59 FR
60535) could have led to the submission of information that was not
relevant to EPA's primary concern of adverse effects caused by the
plant-incorporated protectant. In addition, the proposed requirement
would have applied to some persons who would not necessarily be in a
position to know if adverse effects had occurred. Therefore, EPA has
revised the language of the regulatory text at 40 CFR 174.71 of the
final rule to clarify that the Agency's intention is to provide a
mechanism for reporting information on adverse effects related to a
plant-incorporated protectant in a plant, and that only persons who
``produce'' plant-incorporated protectants for sale and distribution
are responsible for submitting information to EPA. This requirement
applies to the person who manufactures, for sale or distribution, a
plant-incorporated protectant. It does not apply, for example, to
researchers performing field experiments, nor to breeders making
crosses among plant varieties with the goal of developing new plant
varieties, nor to a person who only sells propagative materials (e.g.,
seed) to farmers without producing the propagative materials
themselves.
    During interagency discussion on this final rule, the question was
posed of whether the commonly observed phenomenon of emergence of
resistance in a pest population to one variety of plant, which
necessitates the replacement of that one variety by another variety of
the same crop plant, would be considered reportable by EPA under 40 CFR
174.71. EPA recognizes that this phenomenon occurs continually in
agriculture and is one of the primary reasons that conventional plant
breeding programs were instituted and continue to be needed by farmers.
Plant breeders must continually develop plant varieties to counter the
evolution in pest populations of the ability to be able to successfully
attack a previously resistant variety. EPA, when it evaluated plants in
sexually compatible populations for potential exemption from the
requirements of FIFRA, took this phenomenon into account. Although in
some instances, e.g., for Bt plant-incorporated protectants, the
evolution of resistance to a pesticide in pest populations is of
concern (Ref. 51), based on the history of plant breeding, adaptation
between pest and plants in populations of sexually compatible plants
derived through conventional breeding should not trigger adverse
effects reporting under Sec. 174.71.
    b. Guidance on adverse effects reporting. To further address the
comment that this requirement may lead to over-reporting, EPA has
clarified both the procedures for reporting and the types of incidents
that must be reported to meet the reporting requirement at 40 CFR
174.71. The text at 40 CFR 174.71 describes the conditions under which
reporting should occur, the information which, if available, should be
provided in the report, and where the reports should be directed at the
EPA. In addition, EPA intends to develop specific guidance to provide
further assistance to avoid confusion and unnecessary reporting. For
example, the guidance would reiterate that this final rule does not
require researchers to notify or consult with EPA, unless they are
selling or distributing the plant-incorporated protectant to the
public. As indicated previously, producers who sell or distribute an
otherwise exempt plant-incorporated protectant must only notify EPA if
they have information on actual adverse effects. Furthermore, this
final rule does not require anyone, including researchers, to maintain
any records.
    EPA, in developing the adverse effects reporting requirement at 40
CFR 174.71 for otherwise exempt plant-incorporated protectants, was
cognizant that in rare circumstances unanticipated effects may occur
with a plant-incorporated protectant. For example, although the Agency
judges it highly unlikely, it is possible that a celery variety
expressing, for pesticidal purposes, high enough levels of psoralen, to
cause dermatitis in humans, could arrive on the market. A celery
variety expressing such levels emerged from the varietal development
programs once in the past 50 years (Ref. 7). It is to enable the
Federal government to address quickly circumstances of this magnitude
that EPA implements the reporting requirement at Sec. 174.71 for
otherwise exempt plant-incorporated protectants.
    If the producer believes the effect is due to consumption of a food
but is unsure whether the effect was due to a plant-incorporated
protectant, the incident must still be reported to EPA. While reports
on human health would be made to EPA, EPA will share such reports with
FDA, and EPA and FDA

[[Page 37807]]

will make a determination of whether any action is necessary to protect
the public health, and if so, what constitutes appropriate action.
    c. Relationship of 40 CFR 174.71 reporting requirement to other
reporting requirements. The reporting requirements imposed upon
registrants under FIFRA section 6(a)(2) for registered pesticides
(including registered plant-incorporated protectants), and under 40 CFR
152.50(f)(3) for applicants for a registration are not affected by this
provision. Nor would either 6(a)(2) or 40 CFR 152.50(f)(3) apply to
those who would be subject to 40 CFR 174.71.
    5. Statutory finding. EPA concludes that plant-incorporated
protectants, derived through conventional breeding from plants sexually
compatible with the recipient plant, as described at 40 CFR 174.25,
warrant exemption under FIFRA section 25(b) because these substances
are of a character that is unnecessary to be subject to FIFRA in order
to carry out the purposes of the Act. EPA makes this finding with
respect to both active and inert ingredients derived through
conventional breeding from sexually compatible plants.
    As discussed above, EPA has determined that plant incorporated
protectants derived through conventional breeding from sexually
compatible plants, pose a low probability of risk to humans and the
environment. As explained in this preamble, and in the tolerance
exemptions for the residues of such plant-incorporated protectants
published elsewhere in this issue of the Federal Register, EPA has
determined that there is a reasonable certainty that no harm will
result from aggregate exposure to the residues of such products,
including all anticipated dietary residues and all other exposures for
which there is reliable information. EPA has also determined that these
pesticide products pose a low probability of non-dietary risks to
humans and the environment. The Agency bases these conclusions on
information from the fields of plant genetics, plant physiology,
phytopathology, microbial ecology, ecology, biochemistry, and plant
breeding, supplemented by the hundreds, if not thousands, of years of
experience growing and consuming plants that contain the substances
that are the subject of this exemption, and by Agency knowledge of
horticultural and agricultural practices.
    EPA has also determined that the use of plant-incorporated
protectants is not likely to cause unreasonable adverse effects on the
environment in the absence of regulatory oversight other than the
adverse effects reporting requirement at 40 CFR 174.71.
    The remaining low probability of risks, both dietary and non-
dietary human risk, as well as all environmental risks, were weighed
against the potential benefits to determine whether, these remaining
risks outweigh the benefits in the absence of regulatory oversight.
Despite the very low level of remaining risks, and the significant
potential benefits, EPA concluded that the balance between the two was
extremely close. This was based on several considerations. First, the
action at issue is an exemption, which could complicate EPA's ability
to respond in the unlikely event a problem should arise. Moreover, the
nature of the potential risks of these products themselves present
particular regulatory challenges. Both the nature of the possible
hazards and the exposure considerations presented by the potential for
the plant's genetic material to spread to wild relatives, weigh heavily
in any risk benefit balance. In addition, because it is an exemption,
EPA bears the burden of both adducing the necessary evidence to support
the rulemaking, and ensuring that the facts continue to support the
exemption over time. Given the breadth of the exemption, EPA believed
that it could not ensure over time that it could continue to support a
finding that the benefits outweigh the risks in the complete absence of
regulatory oversight.
    But EPA does not believe that the potential risks outweigh the
benefits to a degree that would warrant the pre-market approval system
of registration. As described throughout this preamble, even though the
nature of the risks are substantial, the probability of the risks is
slight. In general, EPA believes that, given the probability of the
potential risks there would be a minimal societal benefit in imposing
the full degree of pre-market and post-market oversight associated with
FIFRA registration. Rather, EPA believes that the imposition of the
adverse effects reporting requirement, when taken with the other
conditions of the FIFRA and FFDCA exemptions, tips the balance of the
risks and benefits. The reporting requirement will allow the Agency to
ensure that the exempted plant-incorporated protectants will continue
to meet the conditions of the exemption, and will provide a mechanism
to monitor the effects of this class of products. Further, because the
exemption is expressly conditioned on the levels of the pesticidal
substance remaining at levels that will not be injurious or deleterious
to human health, EPA and FDA will be able to address the risk presented
by a particular plant-incorporated protectant should a toxicant or high
levels of a toxicant occur in the food supply, without the need to
revoke the exemption. This permits some continuing degree of post-
market oversight analogous to that provided through the registration
process.

E. Establishment of 40 CFR Part 174

    EPA received three comments addressing the establishment of new 40
CFR part 174. All of the comments supported the Agency's proposed rule.
    As proposed in the 1994 Federal Register document, EPA establishes
a new 40 CFR part 174. The new part will consolidate regulations
specifically applicable to plant-incorporated protectants into one part
of the CFR. EPA believes that establishment of a new part specifically
for plant-incorporated protectants is appropriate and justified because
of the characteristics that distinguish plant-incorporated protectants
from other types of pesticides. This consolidation is expected to
benefit the public by providing greater focus, enhanced clarity and
ease of use. The regulatory requirements found in 40 CFR part 174 apply
to plant-incorporated protectants only. Regulations in 40 CFR part 174
supersede other pesticide regulations found in 40 CFR parts 150 through
173 and 40 CFR parts 177 through 180 when these regulations conflict
with a regulation in 40 CFR part 174. Unless otherwise superseded by 40
CFR part 174, the regulations in 40 CFR parts 150 through 173 apply to
plant-incorporated protectants.
    In this final rule, EPA establishes subparts in 40 CFR part 174 to
contain either regulations EPA is implementing through this rule, or
regulations EPA may implement in the future, tailored to apply
specifically to plant-incorporated protectants. EPA has numbered and
organized 40 CFR part 174 somewhat differently in this final rule than
proposed in the November 23, 1994, Federal Register document (59 FR
60533), in part to provide greater flexibility for including future
regulations at 40 CFR part 174, and for greater ease of use.
    In 40 CFR part 174, subpart A, ``General Provisions,'' Sec. 174.1
describes the scope and purpose of part 174. For clarification, some
revisions have been made to the language of proposed Sec. 174.1 as it
appeared in proposed subpart A of the November 23, 1994, Federal
Register document (59 FR 60534). Subpart A also contains at

[[Page 37808]]

Sec. 174.3 the definitions relevant to plant-incorporated protectants.
As described elsewhere in this document, some definitions proposed at
Sec. 174.3 in the November 23, 1994, Federal Register document (59 FR
60534) were revised for clarity, to limit the exemption, and to
accommodate the change of name of this type of pesticide from ``plant-
pesticide'' to ``plant-incorporated protectant.'' Subpart A also
describes at Sec. 174.9 procedures for dealing with confidential
business information (CBI) claims for plant-incorporated protectants.
    Subpart B is established in 40 CFR part 174 and describes at
Sec. 174.21 ``General qualifications for exemptions.'' The exemption
promulgated with this final rule is described at Sec. 174.25, ``Plant-
incorporated protectant derived from sexually compatible plant.'' The
proposed rule in the November 23, 1994, Federal Register document (59
FR 60535) described the proposed exemption in proposed subpart A at
Sec. 174.5. The exemption has been described in a separate subpart B,
in the final rule, to facilitate ease of use and ability to easily
expand the list of exemptions.
    Subpart D is established in 40 CFR part 174 for monitoring and
recordkeeping requirements and sets forth requirements for submission
of information regarding adverse effects caused by otherwise exempted
plant-incorporated protectants. In the November 23, 1994, Federal
Register document (59 FR 60535) the proposed language describing this
proposed reporting requirement appeared at proposed 40 CFR 174.7. A
subpart D has been established and the adverse effects reporting
requirement has been placed at Sec. 174.71 in subpart D to establish a
distinct subpart for monitoring and recordkeeping requirements. The
establishment of this subpart should facilitate ease of use by the
regulated community.
    Subpart C is established and reserved in 40 CFR part 174 for
registration procedures and requirements. Similarly, subparts E through
V are established and reserved in 40 CFR part 174 for regulations
addressing other activities associated with plant-incorporated
protectants; e.g., labeling, data requirements and experimental use
permits. It is anticipated that future rulemakings will address these
activities specifically for plant-incorporated protectants, and that
the final regulations for these activities will be placed in these
subparts.
    Subpart W is established in 40 CFR part 174 to contain tolerances
and exemptions from the requirement of a tolerance for plant-
incorporated protectants under FFDCA section 408. Because 40 CFR part
174 did not exist at the time of the publication of the proposals to
exempt certain categories of residues of plant-incorporated protectants
(59 FR 60535, 60542, 60545) from the FFDCA requirement of a tolerance,
the proposals were presented as amendments to 40 CFR part 180. With the
establishment of 40 CFR part 174 through this final rule, the
exemptions from the requirement of a tolerance published in companion
documents elsewhere in this issue of the Federal Register are listed at
40 CFR 174.475, ``Nucleic acids that are part of a plant-incorporated
protectant; exemption from the requirement of a tolerance'', and at
Sec. 174.479, ``Pesticidal substance derived from sexually compatible
plant; exemption from the requirement of a tolerance''. Tolerances or
exemptions from the requirement of a tolerance issued for plant-
incorporated protectants prior to establishment of 40 CFR part 174 and
thus currently listed at 40 CFR part 180 will be moved in the near
future to 40 CFR part 174, subpart W. It is anticipated that
establishment of subpart W in 40 CFR part 174 will facilitate ease of
the use of the CFR for the general community, particularly those
manufacturing and using plant-incorporated protectants.
    A subpart X is established in 40 CFR part 174 and titled ``List of
Approved Inert Ingredients.'' At Sec. 174.485 EPA, EPA lists inert
ingredients from sexually compatible plants.

F. Upfront Substantiation of Confidential Business Information

    EPA continues to believe that substantiation of CBI claims for
plant-incorporated protectants at the time of submission of information
to the Agency will help to ensure a timely response to submissions for
plant-incorporated protectants, further the public's right to access
information and, consistent with FIFRA, protect confidential business
information. EPA has concluded that up-front substantiation of CBI
claims does not invalidate or jeopardize legitimate CBI claims. The
Agency recognizes that the regulated community has a legitimate and
legally cognizable interest in protecting trade secrets and other CBI.
EPA has concluded that the requirement at 40 CFR 174.9 in the final
rule allows the Agency to respond to requests for access to
information, provide (where appropriate) expurgated copies of
submissions and a rationale for any exclusions, and where necessary,
make final determinations with respect to the validity of CBI claims
without delaying regulatory action while CBI claims are being
substantiated.
    The release of information prior to registration is controlled in
part by the Freedom of Information Act (FOIA), 5 U.S.C. 552, and
section 10 of FIFRA (7 U.S.C. 136h). FOIA requires Federal agencies to
provide the public with copies of agency records upon request, but
contains exemptions from disclosure. Among those exemptions is one for
``trade secrets and commercial or financial information obtained from a
person and privileged or confidential'' (5 U.S.C. 552(b)(4)). FIFRA
section 10(b) requires protection of the same class of information.
However, section 10(d)(1) limits confidentiality protection for safety
and efficacy data (unless disclosure of such data in turn would
disclose manufacturing or quality control processes, the method for
detecting any deliberately added inert ingredient, or the identity or
percentage quality of any deliberately added inert ingredient) for
registered or previously registered pesticides (7 U.S.C. 136h(d)(1)).
Even these excepted categories must meet the section 10(b) requirements
in order to be protected. Section 3(c)(2)(A) of FIFRA provides for
disclosure of certain non-confidential data 30 days after registration
(7 U.S.C. 136a(c)(2)(A)).
    The Agency received five comments that address the proposed
requirement for up-front substantiation of CBI. Four commenters agreed
with the provision. These commenters generally agreed that up-front
substantiation of CBI claims will help to both ensure that the public
has adequate access to information and provide timely responses to the
regulated community.
    One commenter disagreed with the provision for up-front
substantiation of CBI. The commenter suggested that data developers
would suffer substantial harm to their competitive position if data
were released prematurely and asserted that EPA does not have the
authority to release data to the public prior to a registration
decision.
    After considering these comments, EPA continues to believe that up-
front substantiation of CBI claims is warranted and includes such a
provision at 40 CFR 174.9. The commenter incorrectly implies that
Sec. 174.9 authorizes release of information entitled to confidential
protection. All Sec. 174.9 does is accelerate the process for
determining whether information claimed as confidential is, in fact,
entitled to protection under FIFRA section 10(b). Congress did not
provide for absolute protection of pesticide information prior to
registration; rather, it required the Agency to protect that

[[Page 37809]]

information which lies within the ambit of section 10(b) (7 U.S.C.
136h).
    The proposed rule contained a provision that substantiations that
themselves were claimed as confidential would be presumptively treated
as CBI by the Agency and would not be disclosed except where ordered by
a Federal court, in accordance with 40 CFR 2.205(c) (part of EPA's
general confidentiality regulations at 40 CFR part 2, subpart B). This
proposed provision would not have changed EPA's practice in any way; it
merely echoed the pre-existing agency-wide treatment of CBI
substantiations. Recently, however, the Agency proposed to amend 40 CFR
2.205(c), to eliminate the automatic protection of CBI substantiations
that are themselves claimed confidential (65 FR 52684, August 30,
2000). EPA believes that such treatment of substantiations is no longer
necessary to support the original purpose of the regulation, i.e.,
encouraging businesses to provide sufficient information to support
their claims. Because the Agency is contemplating removing
Sec. 2.205(c) and because the proposed provision in 40 CFR 174.9 merely
echoes the existing more general provision in Sec. 2.205(c), the
Sec. 174.9 provision is not included in this final rule.

VIII. Documents in the Official Record

    As indicated in Unit I.B.2., the official record for this rule has
been established under the docket control number OPP-300369B, 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 are 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-300369, OPP-
300370, OPP-300370A, and OPP-300369A''.
    3. Cook, R. J., and C. O. Qualset. 1996. (Eds) Appropriate
oversight for plants with inherited traits for resistance to pests.
Institute of Food Technologists. Info@ift.org.
    4. National Research Council. 2000. Genetically Modified Pest-
Protected Plants: Science and Regulation. National Academy Press.
Washington DC.
    5. Webster's Unabridged Third New International Dictionary. 1961.
Philip Babcock, Editor-in-Chief. G+C Merriam Co. Springfield
Massachusetts.
    6. H.R. Rep. No. 497, 94th Cong., 1st sess. 36(1975).
    7. International Food Biotechnology Council. 1990. Biotechnologies
and food; Assuring the safety of foods produced by genetic
modification. In: Regulatory Toxicology and Pharmacology. Vol. 12.
Academic Press. New York, New York.
    8. Environmental Protection Agency (EPA) issue paper. 2000. Natural
toxicants in food.
    9. Raven, P. H., R. F. Evert, and S. E. Eichhorn. 1992. Biology of
Plants. Fifth Edition. Worth Publishers, New York, New York.
    10. Cook, R. J., and K. F. Baker. 1993. The nature and practice of
biological control of plant pathogens. APS Press. St. Paul, Minnesota.
    11. Harper, B. K., S. A. Mabon, S. M. Leffel, M. D. Halfhill, H. A.
Richards, K. A. Moyer, and C. N. Steward, Jr. 1999. Green fluorescent
protein as a marker for expression of a second gene in transgenic
plants. Nature Biotechnology. Vol. 17: 1125-1129.
    12. Hoy, M. A. 2000. Current status of biological control of
insects. In: Emerging technologies for integrated pest management.
Edited by G. G. Kennedy and T.B. Sutton. APS Press. St. Paul,
Minnesota.
    13. Hanson, M., and J. Halloran. In a letter dated February 22,
1995 on dockets OPP-300367 through OPP-300371.
    14. Rissler, J., and M. Mellon. In a letter dated January 23, 1995
on dockets OPP-300367 through OPP-300371.
    15. Environmental Protection Agency (EPA). Joint meeting of the EPA
Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory
Panel (SAP), Subpanel on Plant-pesticides and the EPA Biotechnology
Science Advisory Committee (BSAC), Subcommittee on Plant-Pesticides.
January 21, 1994. Final report.
    16. Wilks, H.M., A. Cortes, D. C. Emery, D. J. Halsall, A. R.
Clarke and J. J. Holbrook. 1992. Opportunities and limits in creating
new enzymes. In: Enzyme Engineering XI. Edited by D. S. Clark and D. A.
Estell. Annals of the New York Academy of Sciences. Vol. 672. The New
York Academy of Sciences. New York. New York.
    17. Watson, J. D., N. H. Hopkins, J. W. Roberts, J. A. Steitz and
A. M. Weiner. 1987. Molecular Biology of the Gene. Fourth Edition. The
Benjamin/Cummings Publishing Company, Inc. Menlo Park, California.
    18. Environmental Protection Agency (EPA) issue paper. 1994. FIFRA:
Benefit and environmental risk considerations for inherent plant-
pesticides.
    19. 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.
    20. 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.
    21. 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.
    22. 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.
    23. 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.
    24. 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 American Medical Association
Oct6;282(13)1233-9.
    25. 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.
    26. 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.
    27. 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
National Cancer Institute Apr7;91(7):605-13.
    28. Association of American Feed Control Officials. Model
regulations for pet food at http://

[[Page 37810]]

www.mindspring.com/woofsportusa/aafco.htm; Corey, B. 1991. Life on a
fish farm: Food safety a priority at http://www.fda.gov/bbs/topics/
CONSUMER/CONN00154.htm; Williams, G. W. And J. B. Ward. 1991 The use of
cottonseed meal in animal feed rations:A survey of feed formulators at
htp://agrinet.tamu.edu/tamrc/pubs/cm291.htm;
    29. Agrios, George. 1988. Plant Pathology. Third edition. Academic
Press, New York, New York.
    30. Goodwin, T. W. and E. I. Mercer. 1983. Introduction to Plant
Biochemistry. Pergamon Press. Oxford, New York, Toronto, Sydney, Paris,
Frankfurt.
    31. Atlas, R. and Bartha, R. 1987. Microbial Ecology. Benjamin/
Cummings Publishing Company, Inc. Menlo Park, California.
    32. National Resarch Council. 1999. Hormonally Active Agents in the
Environment. National Academy Press, Washington DC.
    33. Environmental Protection Agency (EPA) issue paper. 1994. Risk
considerations for outcrossing and hybridization.
    34. Doebley, J. 1988. In: ``Transgenic Plant Conference.''
Proceedings of a meeting held September 7-9, 1988, in Annapolis,
Maryland. Pages 137-145. Prepared by the Keystone Center. Frisco,
Colorado.
    35. Lovell, C. R. 1993. Plants and the skin. First edition. Oxford,
Blackwell Scientific Publications.
    36. Environmental Protection Agency (EPA) issue paper. 2000. Dermal
and inhalation exposure to plant substances.
    37. 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.
    38. Environmental Protection Agency. 1997. Exposure Factors
Handbook. Volume 1. National Center for Environmental Assessment. EPA/
600/P-95/002Fa.
    39. Evans, L.T. 1998. Feeding the ten billion: Plants and
population growth. Cambridge University Press. Cambridge, United
Kingdom.
    40. Conway, G. 1998. The doubly green revolution: Food for all in
the 21st century. Cornell University Press, New York. Pp. 44-68.
    41. Duvick D. N. 1984. Genetic contributions to yield gains of US
hybrid maize, 1930 to 1980. In: Genetic contribution yield gains of
five major crop plants. Edited by W. R. Fehr. Crop Science Society of
America Special Publication Number 7. Madison, Wisconsin: CSSA.
    42. Specht, R. F., and J. H. Williams. 1984. Contributions of
genetic technology to soybean productivity - retrospect and prospect.
In: Genetic contribution to yield gains of five major crop plants.
Edited by W. R. Fehr. Crop Science Society of America Special
Publication Number 7. Madison, Wisconsin: CSSA.
    43. Huffman, W. E., and R. E. Evensen. 1993. Science for
agriculture: A long term perspective. Ames: University of Iowa Press.
    44. Miller, F. R., and Y. Kebede. 1984. Genetic contributions to
yield gains on sorghum. In: Genetic contribution yield gains of five
major crop plants. Edited by W. R. Fehr. Crop Science Society of
America Special Publication Number 7. Madison, Wisconsin: CSSA.
    45. Schmidt, J. W. 1984. Genetic contributions to yield gains in
wheat. In: Genetic contribution yield gains of five major crop plants.
Edited by W. R. Fehr. Crop Science Society of America Special
Publication Number 7. Madison, Wisconsin: CSSA.
    46. Feyerherm, A. M., K. E. Kemp, and G. M. Paulsen. 1988. Wheat
yield analysis in relation to advancing technology in the Midwest
United States. Agronomy Journal 80:998-1001.
    47. Bucknell, A. and A. Moxey. 1990. Biotechnology and agriculture.
Food Policy Westbury, United Kingdom, Vol. 15: 44-53.
    48. Hill, L. D. and W. J. Florkowski. 1991. The economics of
biotechnology in field-crop production. Illinois Research, Spring/
Summer. pp. 8-10.
    49. Stanley, J. A. 1991. Agricultural biotechnology: Dividends and
drawbacks. Federal Reserve Bank of Kansas City. Economic Review, May/
June, pp. 43-55.
    50. Environmental Protection Agency (EPA). 2000. Economic analysis
of the plant-incorporated protectant regulations under the Federal
Insecticide, Fungicide, and Rodenticide Act.
    51. Environmental Protection Agency. 1998. The Environmental
Protection Agency's white paper on Bacillus thuringiensis plant-
pesticide resistance management. EPA 739-S-98-001. (http://www.wpa.gov/
fedrgstr/).

B. Additional Information

    The 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)(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-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-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-300371B for
the companion document entitled ``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-

[[Page 37811]]

Incorporated Protectants (Formerly Plant-Pesticides)'' (FRL-6057-5)
published elsewhere in this issue of the Federal Register.
    The docket identified by the docket control number OPP-300370B for
the document entitled ``Plant-Incorporated Protectants; Supplemental
Notice of Availability'' (FRL-6760-4).
    The docket identified by the docket control number OPP-300369B for
this document [FRL-6057-7].
    Also include in the official 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 for this final rule, and supporting
documents (Ref. 50).
    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 documents pertaining to the development
of this final rule (Ref. 2).

IX. Statutory Review Requirements

    In accordance with FIFRA section 25(a), this proposed rule was
submitted to the FIFRA Scientific Advisory Panel, the Secretary of
Agriculture (USDA), and appropriate Congressional Committees. The
Scientific Advisory Panel waived its review of this final rule. Any
changes made in response to comments received from USDA have been
documented in the public version of the official record, along with any
other comments received during the inter-agency review under Executive
Order 12866.

X. Regulatory Assessment

A. Executive Order 12866

    Pursuant to Executive Order 12866 (58 FR 51735, October 4, 1993),
it has been determined that this is a ``significant regulatory action''
because it may raise potentially novel legal or policy issues arising
out of legal mandates, the President's priorities, or the principles
set forth in the Executive Order. Therefore, this action was submitted
to OMB for review, and any comments or changes made during that review
have been documented in the public version of the official record for
this rulemaking.
    EPA has prepared an economic analysis of the impacts related to
this final action, which evaluates the direct costs of regulating
certain types of plant-incorporated protectants and exempting one
specific type of plant-incorporated protectants from FIFRA requirements
(40 CFR part 174) and discusses the non-quantifiable benefits of this
action. Direct compliance costs include cost estimates for the
requirements to substantiate CBI when the claim is made and adverse
effects reporting for otherwise exempt plant-incorporated protectants.
This economic analysis is contained in a document entitled ``Economic
Analysis: Regulations for Plant-Incorporated Protectants Under the
Federal Insecticide, Fungicide, and Rodenticide Act,'' hereinafter
``the EA.'' This document is available as a part of the public version
of the official record for this rulemaking (Ref. 50) and is briefly
summarized here. (See Unit I. for instructions on obtaining support
documents).
    The EA presents the potential costs and benefits associated with
the various requirements considered by the Agency during the
development of the final action. This rule may impose direct compliance
costs of $2.4 million in year 1 and $7.9 million in year 10. The
benefits include the non-quantifiable benefits of assurance of
protection of the environment, a more certain regulatory climate for
industry, and reassurance to the public of the safety of these
products. As such, the Agency believes that the potential annual costs
associated with the exemption is minimal.
    The Agency's EA at the time of proposed rule in 1994 estimated and
compared the costs and benefits associated with four options, ranging
from implementation of regulating few types of plant-incorporated
protectants with exemptions of several types of plant-incorporated
protectants, through implementation of increasing numbers of types of
plant-incorporated protectants regulated and decreasing the exemptions.
The EA for the final rule calculates the direct compliance costs
associated with four similar options. The methodology employed in both
the proposed EA and the final EA is the same. The costs of each of the
four options in the final EA are lower than the costs of the four
options in the EA for the proposed rule. This can, in general, be
attributed to an agreement between EPA and USDA that costs for data
generation would not be ``double counted'', i.e., if USDA required
certain data, EPA would not count the costs of that data in its EA.
Based on the Agency's experience over the past several years, EPA also
lowered its estimate of the probability when more expensive, higher
tiered testing would for required. The Agency also increased its
estimates of projected number of plant-incorporated protectants
submitted annually for registration.
    This rule will also generate a wide range of non-monetized benefits
for the public, the firms involved with agricultural biotechnology, the
environment, nontarget organisms, and states. These benefits include
greater certainty in the regulated community of the status of their
plant- incorporated protectant. Because EPA issued a proposal to exempt
several broad categories of plant-incorporated protectants in 1994,
some uncertainty may exist in industry regarding the status of many
plant-incorporated protectants under FIFRA and this uncertainty may
also be a cost on industry. The final rule will clarify the status of
one category of plant-incorporated protectants and thereby eliminate
some of this uncertainty. With this action, firms developing and
testing plant-incorporated protectants can plan ahead for timely
product development and commercialization, which should, in turn,
attract investors to the agricultural biotechnology sector. States will
benefit by having a set of standardized Federal regulations that will
be more easily conveyed, interpreted, and enforced. In addition,
through this rule, EPA can help reassure the public of the safety of
these types of products; registrants of plant-incorporated protectants
can expend the considerable resources on research and development of
products which may not be accepted by the public if EPA cannot assure
their safety. Industry thus benefits by a reduction of uncertainty
about the acceptability of their products and by greater market
acceptance of the products.

B. Regulatory Flexibility Act (RFA)

    Pursuant to section 605(b) of the Regulatory Flexibility Act (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 factual basis for the Agency's determination is
presented in the small entity impact analysis prepared as part of the
economic analysis for this rule (Ref. 50), and is briefly summarized
here.
    For the purpose of analyzing the potential impacts of this rule on
small entities, EPA used the definition for

[[Page 37812]]

small entities that is found in section 601 of the RFA. Under section
601, ``small entity'' is defined as: (1) A small business that meets
Small Business Administration (SBA) size standards codified at 13 CFR
121.201; (2) a small governmental jurisdiction that is a government of
a city, county, town, school district or special district with a
population of less than 50,000; and (3) a small organization that is
any not-for-profit enterprise which is independently owned and operated
and is not dominant in its field. This rule is not expected to
adversely impact small local governments. EPA's analysis, therefore,
assesses the potential impacts on small not-for-profit organizations
(i.e., universities with $5 million or less in annual revenues under
the SBA size standard for SIC 8221), and small businesses i.e., small
pesticides and agricultural chemical producers with 500 or less
employees under SBA size standard for SIC 2879.
    In determining whether a rule has a significant economic impact on
a substantial number of small entities, the impact of concern is any
significant adverse economic impact on small entities, since the
primary purpose of the regulatory flexibility analyses is to identify
and address regulatory alternatives ``which minimize any significant
economic impact on [...] small entities.'' 5 U.S.C. sections 603 and
604. Thus, an agency may certify that a rule will not have a
significant economic impact on a substantial number of small entities
if the rule relieves regulatory burden, or otherwise has a positive
economic effects on all of the small entities subject to the rule.
    The aggregate potential impacts of the rule are expected to be
minimal on small pesticide and other chemical manufacturers. Seed
companies were not evaluated separately because the data available
indicate that most seed companies have been purchased by larger, parent
companies, many of which are pesticide manufacturers. The anticipated
impact on universities, colleges, and professional schools cannot be
determined. It appears that a majority of universities and colleges
that would be expected to develop and research plant-incorporated
protectants would not be small. Since small R&D firms lack the
expertise and resources to produce, sell and manufacture plant-
incorporated protectants, the burden of registration will not fall on
specialized R&D firms. The Agency anticipates that many of the R&D
firms with specialized expertise in this area will either work with or
be purchased by larger firms with the expertise and financial resources
to produce, sell, and/or distribute viable plant-incorporated
protectants.
    Information relating to this determination will be provided to the
Chief Counsel for Advocacy of the SBA upon request.

C. Paperwork Reduction Act

    Pursuant to the Paperwork Reduction Act (PRA), 44 U.S.C. 3501 et
seq., an agency may not conduct or sponsor, and a person is not
required to respond to, an information collection request unless it
displays a currently valid OMB control number. The OMB control numbers
for EPA's regulations, after appearing in the preamble of the final
rule, are listed in 40 CFR part 9, and included on the related
collection instrument.
    The information collection requirements contained in this final
rule have been submitted to OMB for review and approval under the PRA
in accordance with the procedures at 5 CFR 1320.11. The burden and
costs related to the information collection requirements contained in
this rule are described in an Information Collection Request (ICR)
identified as EPA ICR No. 1693.02, which has been included in the
public version of the official record described in Unit I.B.2., and is
available electronically as described in Unit I.B.1., at http://
www.epa.gov/opperid1/icr.htm, or by e-mailing a request to
farmer.sandy@epa.gov. You may also request a copy by mail from Sandy
Farmer, Collection Strategies Division, U.S. Environmental Protection
Agency (Mail Code 2822), 1200 Pennsylvania Ave. NW., Washington, DC
20460, or by calling (202) 260-2740.
    As defined by the PRA and 5 CFR 1320.3(b), ``burden'' means the
total time, effort, or financial resources expended by persons to
generate, maintain, retain, or disclose or provide information to or
for a Federal agency. This includes the time needed for rule
familiarization and to review instructions; develop, acquire, install,
and utilize technology and systems for the purpose of collecting,
validating, and verifying information, processing and maintaining
information, and disclosing and providing information; adjust the
existing ways to comply with any previously applicable instructions and
requirements; train personnel to be able to respond to a collection of
information; search data sources; complete and review the collection of
information; and transmit or otherwise disclose the information.
    The information collection requirements contained in this rule
include up-front substantiation for claims of CBI for plant-
incorporated protectant activities (e.g., EUP submissions, registration
applications, tolerance requests, and adverse effects reporting), and
for adverse effects reporting for the otherwise exempt plant-
incorporated protectants. The annual respondent burden associated with
the CBI substantiation and averse effects reporting for exempted plant-
incorporated protectants is estimated to average 352 hours per
submission, with a potential individual respondent burden of 25 hours
for each CBI substantiation required, and 7.8 hours for each adverse
effects reporting event. The annual respondent burden associated with
the CBI substantiation for those plant-incorporated protectants that
are not exempted by this rule is estimated to be 595 hours.

D. Unfunded Mandates Reform Act

    Pursuant to Title II of the Unfunded Mandates Reform Act of 1995
(UMRA), Public Law 104-4, EPA has determined that this action does not
contain a Federal mandate that may result in expenditures of $100
million or more for State, local or tribal governments, in the
aggregate, or on the private sector in any one year. The analysis of
the costs associated with this action are described in Unit X.A.
    The UMRA requirements in sections 202, 204, and 205 do not apply to
this rule, because this action does not contain any ``Federal
mandates'' or impose any ``enforceable duty'' on State/Tribal, or local
governments or on the private sector. The requirements in section 203
do not apply because this rule does not contain any regulatory
requirements that might significantly or uniquely affect small
governments.

E. Executive Order 13132

    Executive Order 13132, entitled ``Federalism'' (64 FR 43255, August
10, 1999) requires EPA to develop an accountable process to ensure
``meaningful and timely input by State and local officials in the
development of regulatory policies that have federalism implications.''
``Policies that have federalism implications'' is defined in the
Executive Order to include regulations that have ``substantial direct
effects on the 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.''
    This final rule does not have federalism implications, because it
will not have substantial direct effects on the States, on the
relationship between the national government and the States, or on the
distribution of power and responsibilities among the various

[[Page 37813]]

levels of government, as specified in Executive Order 13132. The
primary result of this action is to exempt certain pesticides from most
FIFRA requirements. Thus, the requirements of section 6 of the
Executive Order do not apply to this rule.

F. Executive Orders 13084 and 13175

    This rule does not significantly or uniquely affect the communities
of Indian tribal 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 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.

G. Executive Order 12898

    Pursuant to Executive Order 12898 (59 FR 7629, February 11, 1994),
entitled Federal Actions to Address Environmental Justice in Minority
Populations and Low-Income Populations, the Agency has considered
environmental justice related issues with regard to the potential
impacts of this action on the environmental and health conditions in
low-income and minority communities. The Agency is required to consider
the potential for differential impacts on sensitive sub-populations.
EPA considered available information on the sensitivities of subgroups
as pertains to the exemptions. EPA concluded that no subgroup would be
differentially affected. (See also the exemptions from the FFDCA
section 408 requirement of a tolerance for residues of nucleic acids
that are part of a plant-incorporated protectant and residues of plant-
incorporated protectants derived through conventional breeding from
sexually compatible plants published elsewhere in companion documents
in this issue of the Federal Register).

H. Executive Order 13045

    Executive Order 13045, entitled: Protection of Children from
Environmental Health Risks and Safety Risks (62 FR 19885, April 23,
1997), does not apply to this rule because it is not economically
significant as defined in section 3(f) of Executive Order 12866, and
because the Agency does not have reason to believe that the
environmental health or safety risks addressed by this action present
disproportionate risks to children. The Agency has determined that the
plant-incorporated protectants exempted in the rule pose only a low
probability of risk to human health, including the health of infants
and children, and that there is a reasonable certainty no harm will
result to infants and children from aggregate exposure to residues of
these plant-incorporated protectants in food. Existing information
suggests there are no disproportionate effects on infants or children
from dietary or other exposures. EPA's assessment and the results of
its assessment for infants and children are contained in Unit IX.B.10.
of companion documents published elsewhere in this issue of the Federal
Register exempting from the FFDCA section 408 requirement of a
tolerance, residues of plant-incorporated protectants derived through
conventional breeding from sexually compatible plants, and residues of
nucleic acids that are part of a plant-incorporated protectant.

I. Voluntary Consensus Standards

    This rule does not involve a regulatory action that would require
the Agency to consider 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). Section 12(d) directs EPA to use voluntary consensus standards
in its regulatory activities unless to do so would be inconsistent with
applicable law or otherwise impractical. Voluntary consensus standards
are technical standards (e.g., materials specifications, test methods,
sampling procedures, business practices, etc.). that are developed or
adopted by voluntary consensus standards bodies. The NTTAA requires EPA
to provide Congress, through OMB, explanations when the Agency decides
not to use available and applicable voluntary consensus standards when
the NTTAA directs the Agency to do so.

J. Executive Order 12630

    EPA has complied with Executive Order 12630, entitled Governmental
Actions and Interference with Constitutionally Protected Property
Rights (53 FR 8859, March 15, 1988), by examining the takings
implications of this rule in accordance with the ``Attorney General's
Supplemental Guidelines for the Evaluation of Risk and Avoidance of
Unanticipated Takings'' issued under the Executive Order.

K. Executive Order 12988

    In issuing this rule, EPA has taken the necessary steps to
eliminate drafting errors and ambiguity, minimize potential litigation,
and provide a clear legal standard for affected conduct, as required by
section 3 of Executive Order 12988, entitled Civil Justice Reform (61
FR 4729, February 7, 1996).

L. FIFRA section 25(a)(2)(b)

    FIFRA section 25(a)(2)(b), requires that the Administrator of EPA
consider such factors as ``. . . the effect of the regulation on
production and prices of agricultural commodities, retail food prices,
and otherwise on the agricultural economy. . .'' when issuing
regulations under section 25 (7 U.S.C. 136w(a)(2)(B). The total direct
compliance costs for the rule were estimated to be $2.4 in year 1 and
$7.9 in year 10. Based on the 1997 Agricultural Census, total U.S. crop
production was valued at $98 billion. The impact of these requirements
will not have a significant impact on U.S. crop production or prices.
The compliance costs of the rule will affect those who plan to
register, manufacture and sell plant-incorporated protectants. This
rule is expected to have a minimal impact on pesticide and other
chemical manufacturers who in turn will sell the plant-incorporated
protectants to agricultural producers. Factors, other than this rule,
that occur as a result of the production of genetically altered
products (i.e., consumer acceptance and the international market desire
to separately market genetically altered products in the market) may
affect agricultural producers and international markets. This rule may
provide some benefits to the agricultural industry by helping to ensure
the public on the safety of these products and positively affect
consumer acceptance.

M. Executive Order 13211

    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.

XI. 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

[[Page 37814]]

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
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 Comptroller General of
the United States prior to publication of the rule in the Federal
Register. This rule is not a ``major rule'' as defined by 5 U.S.C.
804(2).

List of Subjects in 40 CFR Parts 152 and 174

    Environmental protection, Administrative practice and procedures,
Pesticides and pests, Reporting and recordkeeping requirements.

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

    Therefore, 40 CFR chapter I is amended as follows:

    1. By amending part 152 as follows:

PART 152--[AMENDED]

    a. The authority citation for part 152 continues to read as
follows:

    Authority: 7 U.S.C. 136-136y; subpart U is also issued under 31
U.S.C. 9701.

    b. Sec. 152.1 is revised to read as follows:

Sec. 152.1  Scope.

    Except as provided in part 174, part 152 sets forth procedures,
requirements, and criteria concerning the registration and
reregistration of pesticide products under FIFRA sec. 3, and for
associated regulatory activities affecting registration. These latter
regulatory activities include data compensation and exclusive use
(subpart E), and the classification of pesticide uses (subpart I). Part
152 also sets forth procedures, requirements, and criteria applicable
to plant-incorporated protectants. Unless specifically superceded by
part 174, the regulations in part 152 apply to plant-incorporated
protectants.

    c. In Sec. 152.3, by removing the paragraph designations,
alphabetizing the terms, alphabetically inserting the new definitions
listed below, and revising the definitions for ``active ingredient''
and ``inert ingredient'' to read as follows:

Sec. 152.3  Definitions.

* * * * *
    Active ingredient means any substance (or group of structurally
similar substances if specified by the Agency) that will prevent,
destroy, repel or mitigate any pest, or that functions as a plant
regulator, desiccant, or defoliant within the meaning of FIFRA sec.
2(a), except as provided in Sec. 174.3 of this chapter.
* * * * *
    Genetic material necessary for the production means both: Genetic
material that encodes a substance or leads to the production of a
substance, and regulatory regions. It does not include noncoding,
nonexpressed nucleotide sequences.
    In a living plant means inside the living plant, on the surface of
the livingplant, or as an exudate from the living plant.
    Inert ingredient means any substance (or group of structurally
similar substances if designated by the Agency), other than an active
ingredient, which is intentionally included in a pesticide product,
except as provided by Sec. 174.3 of this chapter.
* * * * *
    Living plant means a plant, plant organ, or plant part that is
alive, viable, ordormant. Examples of plant parts include, but are not
limited to, seeds, fruits, leaves, roots, stems,flowers, and pollen.
* * * * *
    Noncoding, nonexpressed nucleotide sequences means the
nucleotidesequences are not transcribed and are not involved in gene
expression. Examples of noncoding,nonexpressed nucleotide sequences
include, but are not limited to, linkers, adapters, homopolymers, and
sequences ofrestriction enzyme recognition sites.
* * * * *
    Pesticidal substance, when referring to a plant-
incorporatedprotectant only, means a substance that is intended to be
produced and used in a living plant, or inthe produce thereof, for a
pesticidal purpose during any part of a plant's life cyle (e.g., in
theembryo, seed, seedling, mature plant).
    Plant-incorporated protectant means a pesticidal substance that
isintended to be produced and used in a living plant, or in the produce
thereof, and the geneticmaterial necessary for production of such a
pesticidal substance. It also includes any inertingredient contained in
the plant, or produce thereof.
    Produce thereof, when referring to plant-incorporated
protectantsonly, means a product of a living plant containing a plant-
incorporated protectant, where thepesticidal substance is intended to
serve a pesticidal purpose after the product has been separatedfrom the
living plant. Examples of such products include, but are not limited
to, agriculturalproduce, grains, and lumber. Products such as raw
agricultural commodities bearing pesticidechemical residues are not
``produce thereof'' when the residues are not intended to serve
apesticidal purpose in the produce.
    Regulatory region means genetic material that controls
theexpression of the genetic material that encodes a pesticidal
substance or leads to the production ofa pesticidal substance. Examples
of regulatory regions include, but are not limited to, promoters,
enhancers, andterminators.
* * * * *

    d. In Sec. 152.20, by revising paragraph (a)(1) and adding
paragraph (a)(4)to read as follows:

Sec. 152.20  Exemptions for pesticidesregulated by another Federal
agency.

* * * * *
    (a) * * *
    (1) Except as provided by paragraphs (a)(3) and (a)(4) of this
section, all biologicalcontrol agents are exempt from FIFRA
requirements.
* * * * *
    (4) All living plants intended for use as biological control agents
are exempt from therequirements of FIFRA. However, plant-incorporated
protectants are not exempt pursuant to thissection. Regulations,
including exemptions, for plant-incorporated protectants are addressed
inpart 174 of this chapter.
* * * * *

    2. By adding a new part 174 to read as follows:

PART 174--PROCEDURES AND REQUIREMENTS FORPLANT-INCORPORATED
PROTECTANTS

Subpart A--General Provisions
Sec.
174.1  Scope and purpose.
174.3  Definitions.
174.9  Confidential business information claims for plant-
incorporated protectant submissions.
Subpart B--Exemptions
174.21  General qualifications for exemptions.
174.25  Plant-incorporated protectant from sexually compatibleplant.
Subpart C--Registration Procedures and Requirements [Reserved]
Subpart D--Monitoring and Recordkeeping
174.71  Submission of information regarding adverse effects.

[[Page 37815]]

Subparts E--F [Reserved]
Subpart G--Labeling Requirements [Reserved]
Subpart H--Data Requirements [Reserved]
Subpart I--[Reserved]
Subpart J--Good Laboratory Practices [Reserved]
Subpart K--Export Requirements [Reserved]
Subparts L--T [Reserved]
Subpart U--Experimental Use Permits [Reserved]
Subpart V--[Reserved]
Subpart W--Tolerances and Tolerance Exemptions
174.451  Scope and purpose.
Subparts X--List of Approved Inert Ingredients
174.480  Scope and purpose.
174.485  Inert ingredients from sexually compatible plant.
Subpart Y--Z [Reserved]

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

Subpart A--General Provisions

Sec. 174.1  Scope and purpose.

    The characteristics of plant-incorporated protectants such as their
production and use inplants, their biological properties, and their
ability to spread and increase in quantity in theenvironment
distinguish them from traditional chemical pesticides. Therefore,
plant-incorporatedprotectants are subject to some different regulatory
requirements and procedures than traditionalchemical pesticides. This
part sets forth regulatory requirements, criteria, and
proceduresapplicable to plant-incorporated protectants under FIFRA and
FFDCA. When applied toplant-incorporated protectants, the definitions
and regulations in this part supercede theregulations found in parts
150 through 180 of this chapter to the extent that the
regulationsconflict. Unless otherwise superceded by this part, the
regulations in parts 150 through 180 of thischapter apply to plant-
incorporated protectants.

Sec. 174.3  Definitions.

    Terms used in this part have the same meaning as in FIFRA. In
addition, the following termshave the meaning set forth in this
section.
    Active ingredientmeans a pesticidal substance that is intended to
be produced and used in a living plant, or in theproduce thereof, and
the genetic material necessary for the production of such a
pesticidalsubstance.
    Administrator means the Administrator of the United States
EnvironmentalProtection Agency or his/her delegate.
    Bridging crosses between plants means the utilization of
anintermediate plant in a cross to produce a viable zygote between the
intermediate plant and a firstplant, in order to cross the plant
resulting from that zygote with a third plant that would nototherwise
be able to produce viable zygotes from the fusion of its gametes with
those of the firstplant. The result of the bridging cross is the mixing
of genetic material of the first and third plantthrough the formation
of an intermediate zygote.
    Cell fusion means the fusion in vitro of two ormore cells or
protoplasts.
    Conventional breeding of plants means the creation of
progenythrough either: The union of gametes, i.e., syngamy, brought
together through processes such aspollination, including bridging
crosses between plants and wide crosses, or vegetative reproduction. It
does not include use of any of the following technologies: Recombinant
DNA;other techniques wherein the genetic material is extracted from an
organism and introduced intothe genome of the recipient plant through,
for example, micro-injection, macro-injection, micro-encapsulation; or
cell fusion.
    EPA means the United States Environmental Protection Agency.
    Exudate means a substance gradually discharged or secreted
acrossintact cellular membranes or cell walls and present in the
intercellular spaces or on the exteriorsurfaces of the plant.
    FFDCA means the Federal Food, Drug, and Cosmetic Act (21 U.S.C.
321et seq.).
    FIFRA means the Federal Insecticide, Fungicide, and Rodenticide
Act, asamended (7 U.S.C. 136 et seq.).
    Food includes articles used for food or drink by humans or
otheranimals.
    Food plant means a plant which either in part or intoto, is used as
food.
    Genetic material necessary for the production means both: Genetic
material that encodes a substance or leads to the production of a
substance; and regulatory regions. It does not include noncoding,
nonexpressed nucleotide sequences.
    Genome means the sum of the heritable genetic material in the
plant, including genetic material in the nucleus and organelles.
    In a living plant means inside the living plant, on the surface of
the livingplant, or as an exudate from the living plant.
    Inert ingredient, means any substance, such as a selectable marker,
other than the active ingredient, where thesubstance is used to confirm
or ensure the presence of the active ingredient, and includes the
geneticmaterial necessary for the production of the substance, provided
that genetic material isintentionally introduced into a living plant in
addition to the active ingredient.
    Living plant means a plant, plant organ, or plant part that is
alive, viable, ordormant. Examples of plant parts include, but are not
limited to, seeds, fruits, leaves, roots, stems,flowers, and pollen.
    Noncoding, nonexpressed nucleotide sequences means the
nucleotidesequences are not transcribed and are not involved in gene
expression. Examples of noncoding,nonexpressed nucleotide sequences
include, but are not limited to, linkers, adapters, homopolymers, and
sequences ofrestriction enzyme recognition sites.
    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 asdeoxyribonucleic
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
containingnucleic acid analogues.
    Pesticidal substance, means a substance that is intended to be
produced and used in a living plant, orin the produce thereof, for a
pesticidal purpose, during any part of a plant's life cyle (e.g., in
theembryo, seed, seedling, mature plant).
    Plant, for plant-incorporated protectants, means an
organismclassified using the 5-kingdom classification system of
Whittaker in the kingdom Plantae. Thisincludes, 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.
    Plant-incorporated protectant means a pesticidal substance that is
intendedto be produced and used in a living plant, or in the produce
thereof, and the genetic materialnecessary for production of such a
pesticidal substance. It also includes any inert ingredientcontained in
the plant, or produce thereof.

[[Page 37816]]

    Produce thereof, when used with respect to plants containing plant-
incorporated protectants only, means a product of a living plant
containing a plant-incorporatedprotectant, where the pesticidal
substance is intended to serve a pesticidal purpose after theproduct
has been separated from the living plant. Examples of such products
include, but are notlimited to, agricultural produce, grains, and
lumber. Products such as raw agriculturalcommoditiesbearing pesticide
chemical residues are not ``produce thereof'' when the residues are not
intendedto serve a pesticidal purpose in the produce.
    Recipient plant means the living plant in which theplant-
incorporated protectant is intended to be produced and used.
    Recombinant DNA means the genetic material has been manipulatedin
vitro through the use of restriction endonucleases and/or other enzymes
that aid in modifyinggenetic material, and subsequently introduced into
the genome of the plant.
    Regulatory region means genetic material that controls
theexpression of the genetic material that encodes a pesticidal
substance or leads to the production ofa pesticidal substance. Examples
of regulatory regions include, but are not limited to, promoters,
enhancers, andterminators.
    Sexually compatible, when referring to plants, means a viable
zygoteis formed only through the union of two gametes through
conventional breeding.
    Source means the donor of the genetic material that encodes
apesticidal substance or leads to the production of a pesticidal
substance.
    Vegetative reproduction means either:
    (1) In seed plants, reproduction by apomixis, or
    (2) In other plants, reproduction by fragmentation, or division of
the somatic body.
    Wide crosses means to facilitate the formation of viable
zygotesthrough the use of surgical alteration of the plant pistil, bud
pollination, mentor pollen,immunosuppressants, in vitro fertilization,
pre-pollination and post-pollination hormone treatments,manipulation of
chromosome numbers, embryo culture, or ovary and ovule cultures.

Sec. 174.9  Confidential businessinformation claims for plant-
incorporated protectant submissions.

    Although it is strongly recommended that the submitter minimize the
amount of dataand other information claimed as Confidential Business
Information (CBI), a submitter may asserta claim of confidentiality for
all or part of the information submitted to EPA in a submission for
aplant-incorporated protectant. (See part 2, subpart B of this
chapter.) To assert such a claim, thesubmitter must comply with all of
the following procedures:
    (a) Any claim of confidentiality must accompany the information at
the time theinformation is submitted to EPA. Failure to assert a claim
at that time constitutes a waiver ofconfidentiality for the information
submitted, and the information may be made available to thepublic,
subject to section 10(g) of FIFRA, with no further notice to the
submitter.
    (b) Any claim of confidentiality must be accompanied, at the time
the claim is made,by comments substantiating the claim and explaining
why the submitter believes that theinformation should not be disclosed.
The submitter must address each of the points listed inSec. 2.204(e)(4)
of this chapter in the substantiation. EPA will consider incomplete
allplant-incorporated protectant submissions containing information
claimed as CBI that are notaccompanied by substantiation, and will
suspend any applicable review of such submissionsuntil the required
substantiation is provided.

Subpart B--Exemptions

Sec. 174.21  General qualifications forexemptions.

    A plant-incorporated protectant is exempt from the requirements of
FIFRA, other than therequirements of Sec. 174.71, if it meets all of
the following criteria:
    (a) The plant-incorporated protectant meets the criteria listed in
at least one of thesections in Sec. Sec. 174.25 through 174.50.
    (b) When the plant-incorporated protectant is intended to be
produced and used in acrop used as food, the residues of the plant-
incorporated protectant are either exempted from therequirement of a
tolerance under FFDCA (as amended, 21 U.S.C. 321 et seq.) ascodified at
Sec. Sec. 174.475 through 174.479, or no tolerance wouldotherwise be
required for the plant-incorporated protectant.
    (c) Any inert ingredient that is part of the plant-incorporated
protectant is on the listcodified at Sec. Sec. 174.485 through
174.490.Plant-incorporated protectants that are not exempt from the
requirements of FIFRA under thissubpart are subject to all the
requirements of FIFRA.

Sec. 174.25  Plant-incorporated protectantfrom sexually compatible
plant.

    A plant-incorporated protectant is exempt if all of the following
conditions are met:
    (a) The genetic material that encodes the pesticidal substance or
leads to theproduction of the pesticidal substance is from a plant that
is sexually compatible with the recipientplant.
    (b) The genetic material has never been derived from a source that
is not sexuallycompatible with the recipient plant.

Subpart C--Registration Procedures and Requirements [Reserved]

Subpart D--Monitoring and Recordkeeping

Sec. 174.71  Submission of informationregarding adverse effects.

    (a) Any person who produces, for sale or distribution, a plant-
incorporated protectantexempt under subpart B of this part, who obtains
any information regarding adverse effects onhuman health or the
environment alleged to have been caused by the plant-incorporated
protectantmust submit such information to EPA. This requirement does
not apply to any person who does not produce a plant-incorporated
protectant exempt under supart B of this part. This may include, for
example, researchers performing field experiments, breeders making
crosses among plant varieties with the goal of developing new plant
varieties, or a person who only sells propagative materials (e.g.,
seed) to farmers without producing the propagative materials
themselves. EPA must receive the report within 30 calendar days of
thedate the producer first possesses or knows of the information.
    (b) Adverse effects on human health or the environment for purposes
of plant-incorporated protectant means at a minimum information about
incidents affecting humans orother nontarget organisms where both:
    (1) The producer is aware, or has been informed, that a person or
nontarget organismallegedly suffered a toxic or adverse effect due to
exposure to (e.g., ingestion of) a plant-incorporated protectant.
    (2) The producer has or could reasonably obtain information
concerning where theincident occurred.
    (c) All of the following information, if available, must be
included in a report.
    (1) Name of reporter, address, and telephone number.
    (2) Name, address, and telephone of contact person (if different
than reporter).

[[Page 37817]]

    (3) Description of incident.
    (4) Date producer became aware of incident.
    (5) Date of incident.
    (6) Location of incident.
    (d) Mail reports and questions to: Biopesticides and Pollution
Prevention Division (7511C), Office of Pesticide Programs,
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460 or deliver reports and questions to: Crystal Mall
#2, Room 910, 1921 Jefferson Davis Hwy., Arlington, VA.

Subparts E--F [Reserved]

Subpart G--Labeling [Reserved]

Subpart H--Data Requirements [Reserved]

Subpart I--[Reserved]

Subpart J--Good Laboratory Practices [Reserved]

Subpart K--Export Requirements [Reserved]

Subparts L--T [Reserved]

Subpart U--Experimental Use Permits [Reserved]

Subpart V--[Reserved]

Subpart W-Tolerances and Tolerance Exemptions

Sec. 174.451  Scope and purpose.

    This subpart lists the tolerances and exemptions from the
requirement of a tolerancefor residues of plant-incorporated
protectants in or on raw agricultural commodities, in food, andin
animal feeds.

Subpart X--List of Approved Inert Ingredients

Sec. 174.480  Scope and purpose.

    This subpart lists the inert ingredients that have been exempted
from FIFRA andFFDCA section 408 requirements and may be used in a
plant-incorporated protectant listed insubpart B of this part.

Sec. 174.485  Inert ingredients from sexually compatible plant.

    An inert ingredient, and residues of the inert ingredient, are
exempt if all of the following conditions are met:
    (a) The genetic material that encodes the inert ingredient or leads
to the production of the inert ingredient is derived from a plant
sexually compatible with the recipient food plant.
    (b) The genetic material has never been derived from a source that
is not sexually compatible with the recipient food plant.
    (c) The residues of the inert ingredient are not present in food
from the plant at levels that are injurious or deleterious to human
health.

Subparts Y--Z [Reserved]--Exemptions

Sec. 174.21  General qualifications forexemptions.

    A plant-incorporated protectant is exempt from the requirements of
FIFRA, other than therequirements of Sec. 174.71, if it meets all of
the following criteria:
    (a) The plant-incorporated protectant meets the criteria listed in
at least one of thesections in Sec. Sec. 174.25 through 174.50.
    (b) When the plant-incorporated protectant is intended to be
produced and used in acrop used as food, the residues of the plant-
incorporated protectant are either exempted from therequirement of a
tolerance under FFDCA (as amended, 21 U.S.C. 321 et seq.) ascodified at
Sec. Sec. 174.475 through 174.479, or no tolerance wouldotherwise be
required for the plant-incorporated protectant.
    (c) Any inert ingredient that is part of the plant-incorporated
protectant is on the listcodified at Sec. Sec. 174.485 through
174.490.Plant-incorporated protectants that are not exempt from the
requirements of FIFRA under thissubpart are subject to all the
requirements of FIFRA.

Sec. 174.25  Plant-incorporated protectantfrom sexually compatible
plant.

    A plant-incorporated protectant is exempt if all of the following
conditions are met:
    (a) The genetic material that encodes the pesticidal substance or
leads to theproduction of the pesticidal substance is from a plant that
is sexually compatible with the recipientplant.
    (b) The genetic material has never been derived from a source that
is not sexuallycompatible with the recipient plant.

Subpart C--Registration Procedures and Requirements [Reserved]

Subpart D--Monitoring and Recordkeeping

Sec. 174.71  Submission of informationregarding adverse effects.

    (a) Any person who produces, for sale or distribution, a plant-
incorporated protectantexempt under subpart B of this part, who obtains
any information regarding adverse effects onhuman health or the
environment alleged to have been caused by the plant-incorporated
protectantmust submit such information to EPA. This requirement does
not apply to any person who does not produce a plant-incorporated
protectant exempt under supart B of this part. This may include, for
example, researchers performing field experiments, breeders making
crosses among plant varieties with the goal of developing new plant
varieties, or a person who only sells propagative materials (e.g.,
seed) to farmers without producing the propagative materials
themselves. EPA must receive the report within 30 calendar days of
thedate the producer first possesses or knows of the information.
    (b) Adverse effects on human health or the environment for purposes
of plant-incorporated protectant means at a minimum information about
incidents affecting humans orother nontarget organisms where both:
    (1) The producer is aware, or has been informed, that a person or
nontarget organismallegedly suffered a toxic or adverse effect due to
exposure to (e.g., ingestion of) a plant-incorporated protectant.
    (2) The producer has or could reasonably obtain information
concerning where theincident occurred.
    (c) All of the following information, if available, must be
included in a report.
    (1) Name of reporter, address, and telephone number.
    (2) Name, address, and telephone of contact person (if different
than reporter).

[[Page 37817]]

    (3) Description of incident.
    (4) Date producer became aware of incident.
    (5) Date of incident.
    (6) Location of incident.
    (d) Mail reports and questions to: Biopesticides and Pollution
Prevention Division (7511C), Office of Pesticide Programs,
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460 or deliver reports and questions to: Crystal Mall
#2, Room 910, 1921 Jefferson Davis Hwy., Arlington, VA.

Subparts E--F [Reserved]

Subpart G--Labeling [Reserved]

Subpart H--Data Requirements [Reserved]

Subpart I--[Reserved]

Subpart J--Good Laboratory Practices [Reserved]

Subpart K--Export Requirements [Reserved]

Subparts L--T [Reserved]

Subpart U--Experimental Use Permits [Reserved]

Subpart V--[Reserved]

Subpart W-Tolerances and Tolerance Exemptions

Sec. 174.451  Scope and purpose.

    This subpart lists the tolerances and exemptions from the
requirement of a tolerancefor residues of plant-incorporated
protectants in or on raw agricultural commodities, in food, andin
animal feeds.

Subpart X--List of Approved Inert Ingredients

Sec. 174.480  Scope and purpose.

    This subpart lists the inert ingredients that have been exempted
from FIFRA andFFDCA section 408 requirements and may be used in a
plant-incorporated protectant listed insubpart B of this part.

Sec. 174.485  Inert ingredients from sexually compatible plant.

    An inert ingredient, and residues of the inert ingredient, are
exempt if all of the following conditions are met:
    (a) The genetic material that encodes the inert ingredient or leads
to the production of the inert ingredient is derived from a plant
sexually compatible with th ingredient or leads
to the production of the inert ingredient is derived from a plant
sexually compatible with the recipient food plant.
    (b) The genetic material has never been derived from a source that
is not sexually compatible with the recipient food plant.
    (c) The residues of the inert ingredient are not present in food
from the plant at levels that are injurious or deleterious to human
health.

Subparts Y--Z [Reserved]

[FR Doc. 01-17981 Filed 7-16-01; 11:42 am]
BILLING CODE 6560-50-S