[Federal Register Volume 66, Number 139 (Thursday, July 19, 2001)]
[Rules and Regulations]
[Pages 37772-37817]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-17981]



[[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

  Federal Register / Vol. 66, No. 139 / Thursday, July 19, 2001 / Rules 
and Regulations  

[[Page 37772]]


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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: 
[email protected].

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. [email protected].
    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 
[email protected]. 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]

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