Plant-Incorporated Protectants (Formerly Plant-Pesticides), Supplemental Proposal

Note: EPA no longer updates this information, but it may be useful as a reference or resource.

[Federal Register: July 19, 2001 (Volume 66, Number 139)]
[Proposed Rules]
[Page 37855-37869]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr19jy01-34]

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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 174
[OPP-300370B; FRL-6760-4]
RIN 2070-AC02

Plant-Incorporated Protectants (Formerly Plant-Pesticides),
Supplemental Proposal

Agency: Environmental Protection Agency (EPA).
Action: Supplemental proposal; notice of data availability.

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SUMMARY: EPA solicits additional comment on the exemptions it proposed
in 1994 for plant-incorporated protectants. Specifically, EPA solicits
comment on two alternative regulatory approaches to plant-incorporated
protectants derived from plants sexually compatible with the recipient
plant that the Agency is considering in response to comments received
on the 1994 proposal. EPA requests comment on the issues raised by
commenters in response to EPA's 1994 proposed exemptions for plant-
incorporated protectants derived from sexually compatible plants, as
well as on any new issues presented by the proposed regulatory
alternatives. The Agency is requesting comment on whether a distinction
made on the basis of process is appropriate. EPA is also providing
notice that it has placed the report issued by the National Academy of
Sciences (NAS) entitled ``Genetically Modified Plants: Science and
Regulation'' in the dockets for the rulemakings relating to certain
proposals on plant-incorporated protectants under the Federal
Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal
Food, Drug, and Cosmetic Act (FFDCA). With this supplemental document,
EPA has reopened the comment period for these particular 1994 proposals
to allow the public an opportunity to comment on the information,
analyses, and conclusions in the NAS report pertaining to plant-
incorporated protectants that act primarily by affecting the plant or
are based on viral coat proteins, as well as on specific questions
posed by the Agency.

DATES: Comments, identified by docket control number OPP-300370B, must
be received on or before August 20, 2001.

ADDRESSES: Comments may be submitted by mail, electronically, or in
person. Please follow the detailed instructions for each method as
provided in Unit I. of the SUPPLEMENTARY INFORMATION. To ensure proper
receipt by EPA, it is imperative that you identify docket control
number OPP-300370B in the subject line on the first page of your
response.

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

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

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

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Examples of
Categories NAICS codes potentially
affected entities
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Pesticide manufacturers 32532 Establishments
primarily engaged
in the
formulation and
preparation of
agricultural and
household pest
control chemicals
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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
the life sciences in conducting
research in the
physical,
engineering, or
life sciences,
such as
agriculture and
biotechnology
------------------------------------------------------------------------

This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in this table could also be
affected. The North American Industrial Classification System (NAICS)
codes are 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
questions regarding the applicability of this action to a particular
entity, consult the person listed under FOR FURTHER INFORMATION
CONTACT.

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

1. Electronically. You may obtain electronic copies of this
document, and certain other related documents that might be available
electronically, from the EPA Internet Home Page at http://www.epa.gov/.
To access this document, on the Home Page select ``Laws and
Regulations,'' ``Regulations and Proposed Rules,'' and then look up the
entry for this document under the ``Federal Register--Environmental
Documents.'' You can also go directly to the Federal Register listings
at http://www.epa.gov/fedrgstr/.
2. In person. The Agency has established an official record for
this action under docket control number OPP-300370B. 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

[[Page 37856]]

as the documents that are referenced in those documents. The public
version of the official record does not include any information claimed
as CBI. The public version of the official record, which includes
printed, paper versions of any electronic comments submitted during an
applicable comment period, is available for inspection in the Public
Information and Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall
#2, 1921 Jefferson Davis Hwy., Arlington, VA, from 8:30 a.m. to 4 p.m.,
Monday through Friday, excluding legal holidays. The PIRIB telephone
number is (703) 305-5805.

C. How and to Whom Do I Submit Comments?

You may submit comments through the mail, in person, or
electronically. To ensure proper receipt by EPA, it is imperative that
you identify docket control number OPP-300370B in the subject line on
the first page of your response.
1. By mail. Submit your comments to: Public Information and Records
Integrity Branch (PIRIB), Information Resources and Services Division
(7502C), Office of Pesticide Programs (OPP), Environmental Protection
Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
2. In person or by courier. Deliver your comments to: Public
Information and Records Integrity Branch (PIRIB), Information Resources
and Services Division (7502C), Office of Pesticide Programs (OPP),
Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921
Jefferson Davis Hwy., Arlington, VA. The PIRIB is open from 8:30 a.m.
to 4 p.m., Monday through Friday, excluding legal holidays. The PIRIB
telephone number is (703) 305-5805.
3. Electronically. You may submit your comments electronically by
e-mail to: opp-docket@epa.gov, or you can submit a computer disk as
described above. Do not submit any information electronically that you
consider to be CBI. Avoid the use of special characters and any form of
encryption. Electronic submissions will be accepted in WordPerfect 6.1/
8.0 or ASCII file format. All comments in electronic form must be
identified by docket control number OPP-300370B. Electronic comments
may also be filed online at many Federal Depository Libraries.

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

Do not submit any information electronically that you consider to
be CBI. You may claim information that you submit to EPA in response to
this document as CBI by marking any part or all of that information as
CBI. Information so marked will not be disclosed except in accordance
with procedures set forth in 40 CFR part 2. In addition to one complete
version of the comment that includes any information claimed as CBI, a
copy of the comment that does not contain the information claimed as
CBI must be submitted for inclusion in the public version of the
official record. Information not marked confidential will be included
in the public version of the official record without prior notice. If
you have any questions about CBI or the procedures for claiming CBI,
please consult the person listed under FOR FURTHER INFORMATION CONTACT.

E. What Should I Consider as I Prepare My Comments for EPA?

You may find the following suggestions helpful for preparing your
comments:
1. Explain your views as clearly as possible.
2. Describe any assumptions that you used.
3. Provide copies of any technical information and/or data you used
that support your views.
4. If you estimate potential burden or costs, explain how you
arrived at the estimate that you provide.
5. Provide specific examples to illustrate your concerns.
6. Offer alternative ways to improve the proposed rule or
collection activity.
7. Make sure to submit your comments by the deadline in this
document.
8. To ensure proper receipt by EPA, be sure to identify the docket
control number assigned to this action in the subject line on the first
page of your response. You may also provide the name, date, and Federal
Register citation.

II. Background

A. Statutory Authority

Section 2(u) of FIFRA (7 U.S.C. 136 et seq.) 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)).
The substances plants produce for protection against pests are
pesticides under the FIFRA definition of pesticide, if humans intend to
use these substances for ``preventing, destroying, repelling or
mitigating any pest,'' regardless of whether the pesticidal capability
evolved in the plants, or were introduced through traditional breeding
or through the techniques of modern genetic engineering (e.g.,
recombinant DNA (rDNA)). These substances, produced and used in living
plants, along with the genetic material necessary to produce them, are
called ``plant-incorporated protectants'' by EPA.
FIFRA section 3 provides, with certain limited exceptions, that no
person may sell or distribute in the United States, any pesticide that
is not registered under the Act (7 U.S.C. 136a (a)). Before a product
may be registered as a pesticide under FIFRA, it must be shown that
``when used in accordance with widespread and commonly recognized
practice, it will not generally cause unreasonable adverse effects on
the environment'' (7 U.S.C. 136a (c)(5)). A pesticide causes
``unreasonable adverse effects on the environment'' if it causes ``(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 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)).
EPA is authorized to promulgate regulations under section 3(a),
``[t]o the extent necessary to prevent unreasonable adverse effects on
the environment, [that]
limit the distribution, sale, or use in any
State of any pesticide that is not registered under this Act and that
is not the subject of an experimental use permit under section 5 or an
emergency exemption under section 18'' (7 U.S.C. 136a(a)).
A person may, however, sell and distribute an unregistered
pesticide if EPA exempts the pesticide pursuant to FIFRA section
25(b)(2). FIFRA section 25(b)(2) authorizes EPA to exempt, by
regulation, any pesticide of a character that is unnecessary to be
subject to FIFRA in order to carry out the purposes of the Act (7
U.S.C. 136w(b)(2)).
Section 408 of the FFDCA applies to all ``pesticide chemical
residues'' which are defined as residues of either a ``pesticide
chemical'' or ``any other added substance that is present on or in a
commodity or food primarily as a

[[Page 37857]]

result of the metabolism or other degradation of a pesticide chemical''
(21 U.S.C. 321(q)(2)). The FFDCA defines ``pesticide chemical'' as:
``any substance that is a pesticide within the meaning of the Federal
Insecticide, Fungicide, and Rodenticide Act, including all active and
inert ingredients of such pesticide'' (21 U.S.C. 321(q)(1)).

B. Other Federal Agencies

EPA is the Federal agency primarily responsible for the regulation
of pesticides. 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 for ensuring 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.

III. Proposed Alternative Regulatory Approaches to Plant-
Incorporated Protectants Derived Through Genetic Engineering from
Sexually Compatible Plants

In this Unit, EPA describes the two alternative regulatory
approaches the Agency is considering to address the issues raised in
comment for this class of plant-incorporated protectants. EPA solicits
public comment on any new issues presented by the proposed regulatory
alternatives as well as on the issues raised in comment on the 1994
proposal. The Agency intends to consider public comments and make final
determinations to complete these other rulemakings within 9 to 12
months after the close of the comment period for the supplemental
proposal, which is currently set at 30 days. Until the Agency takes a
final action on these other exemptions, the Agency intends to maintain
its current practices on regulation of plant-incorporated protectants.

A. History

The plant-incorporated protectants that a plant population has
evolved, and thus naturally possesses, can be varied, including, for
example, structural characteristics of the plant, the production of
general 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. The plant-
incorporated protectants that characterize a particular plant
population can be shared among the members of the population by the
process of sexual hybridization. There is a large base of human
experience in selective breeding of plants within sexually compatible
populations using conventional hybridization techniques. There is much
experience growing such plants, and preparing and consuming food from
plants in such populations. Based on this experience and the
information base generated through scientific study of such plants and
their constituents, and on knowledge in plant genetics, plant
physiology, phytopathology, microbial ecology, ecology, plant breeding
and biochemistry, EPA proposed in 1994 to exempt plant-incorporated
protectants that plants normally possess and are moved between closely
related plants. EPA's preferred approach to describing for regulatory
purposes this category of plant-incorporated protectants used the
criterion of sexual compatibility, including hybridization achieved by
wide and bridging crosses.
1. 1994 Proposal. Plants that are sexually compatible form viable
zygotes through the fusion of gametes in sexual hybridization. In the
Federal Register of November 23, 1994 (59 FR 60519), EPA proposed that
plant-pesticides (now plant-incorporated protectants) would be exempt
from all FIFRA requirements, except for an 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. EPA
proposed in 1994 that this exemption for ``sexually compatible'' plant-
incorporated protectants would apply regardless of how a plant-
incorporated protectant came to be in the plant; e.g., whether they
evolved naturally in the plant, or were introduced through traditional
breeding or the techniques of genetic engineering, as long as the donor
and recipient plant are sexually compatible. EPA's proposal to exempt
plant-incorporated protectants from

[[Page 37858]]

sexually compatible plants subsumed plant-incorporated protectants in
plants propagated vegetatively. In 1994, EPA also published companion
proposals under section 408 of the FFDCA that would exempt all residues
of plant-incorporated protectants derived from plants sexually
compatible with the recipient plant (59 FR 60535, 60542). EPA caveated
the 1994 proposals by noting that the Agency did not intend 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 at 60524). In
1994, EPA also offered for comment two alternative proposed approaches
based in whole or in part on taxonomy. All three of these approaches
were based on the premise that closely related plants, whether
described by sexual compatibility or taxonomy, were unlikely to present
novel exposures.
In the 1994 proposals, 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. Basically this described the traditional breeding
techniques of controlled pollination among plants expressing desired
traits, seed collection and selection of the resulting progeny for
enhanced combinations.
In the 1994 proposals, ``bridging crosses between plants`` were
defined as 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.
In the 1994 proposal, ``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- 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.
The Agency also requested in the 1994 Federal Register, comment on
an exemption criterion based on the process (e.g., rDNA) used to
introduce the plant-incorporated protectant into a plant (50 FR at
60514 and 60530). In this approach, plant-incorporated protectants
developed through techniques other than those of modern genetic
engineering (e.g., rDNA) would be exempted, i.e., 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. The FIFRA Scientific Advisory Panel (SAP) and the
Biotechnology Science Advisory Committee at a joint meeting on January
21, 1994, considered the utility of such an approach, and supported use
of a criterion based on rDNA methodologies, based on: the success of
the National Institutes of Health Guidelines for Research Involving
Recombinant DNA Molecules (e.g., see 59 FR 34496, July 5, 1994);
uncertainties about how a gene will function in the new genetic
background; and to build public confidence in the products of genetic
engineering. The joint meeting report also recommended that further
exemptions . . .should be used in conjunction with the criterion based
on methodology. The SAP specifically recommended that ``[f]or example,
when rDNA methodologies are used to exchange genes between sexually
compatible crop plants, the products would be exempt from additional
regulation'' (Ref. 4 at 10).
2. Public comments. In response to its November 23, 1994 Federal
Register request for comment on the proposal to exempt plant-
incorporated protectants derived from plants sexually compatible with
the recipient plant (59 FR at 60533), EPA received 52 comments
addressing the issue of scope of exemption. These comments presented a
broad range of views. Twenty-seven comments discussed the merits of
EPA's 1994 preferred approach; i.e., the exemption proposal based on
sexual compatibility between the donor and recipient plants. The
majority of these comments favored such an approach, although some
commenters favored EPA's alternative proposed approach based in part on
taxonomy (Option 3). Others among the 27 comments expressed reservation
about the rationale underlying the preferred and alternative
approaches, i.e., relatedness among plants being equated to potential
for novel exposures. For example, one comment stated that while
superficially attractive, EPA's preferred approach was flawed in that
it did not consider nontarget exposure by the introduction of a plant
into an ecosystem in which it did not evolve.
EPA also received 35 comments on the propriety of relying on the
process by which the genetic material is introduced into the plant as a
criterion for defining the scope of EPA's regulatory oversight. Twenty
of these comments supported an approach based on process, i.e., that
those plant-incorporated protectants introduced by rDNA would be
regulated, while conventional breeding would be exempt. These comments
urged the Agency not to exempt plant-incorporated protectants
introduced into the recipient plant by the processes of genetic
engineering, regardless of whether they were derived from plants
sexually compatible with the recipient plant. The comments focused on a
common concern, which can be represented by the following excerpt:

Genetic engineering (particularly recombinant DNA [rDNA]
methodologies), represents a fundamental technical advance over
traditional plant breeding in the ability to manipulate plants
genetically. . . . 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. 5).

3. Current status. In companion documents published elsewhere today
in this issue of the Federal Register, EPA exempts plant-incorporated
protectants derived through conventional breeding from sexually
compatible plants. In that document, EPA describes conventional
breeding as 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 the techniques of genetic engineering. It does not
include use of: 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.
In this supplemental document, EPA specifically requests comment on
two proposed alternative regulatory approaches for plant-incorporated
protectants derived through genetic engineering (e.g., rDNA) from
plants sexually compatible with the recipient plant.

B. Description of Alternative Proposals

Under the first alternative, all plant-incorporated protectants
derived from plants sexually compatible with the recipient plant would
be exempt

[[Page 37859]]

regardless of the technique used to introduce the plant-incorporated
protectant into the plant. Under the second alternative, EPA would
establish a notification process that would implement a screening
procedure to determine whether a plant-incorporated protectant derived
through genetic engineering from a plant sexually compatible with the
recipient plant qualified for exemption.
1. Exemption of all plant-incorporated protectants derived from
plants sexually compatible with recipient plant. EPA will review
comment on this supplemental proposal, and reevaluate risk in light of
recent information and the comments. If EPA concludes that all plant-
incorporated protectants derived from plants sexually compatible with
the recipient plant meet the criteria for an exemption from all FIFRA
requirements, except for the adverse effects reporting requirement at
40 CFR 174.71, and the requirements of a tolerance under section 408 of
the FFDCA for the residues of such plant-incorporated protectants, the
following language would be substituted in the regulatory text at 40
CFR part 174.
i. FIFRA. The following language would be substituted at 40 CFR
174.25:

Sec. 174.25 Plant-incorporated protectant from 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 the production of the pesticidal substance is derived
from a plant that is sexually compatible with the recipient plant.
(b) The genetic material that encodes the pesticidal substance
or leads to the production of the pesticidal substance has never
been derived from a source that is not sexually compatible with the
recipient plant.
(c) The active ingredient has not been functionally modified
from the source.

Sexually compatible, when referring to plants, would mean capable
of forming a viable zygote through the union of two gametes, including
the use of bridging crosses or wide crosses between plants. Sexually
compatible would include the recombination that occurs in hybridization
between sexually compatible plants, e.g., the formation of a viable
zygote by the pollination of one corn plant with another. It would also
include plant-incorporated protectants that normally occur in the
plant, when such plants are propagated vegetatively, e.g., banana.
Functionally modified from the source, when referring to plant-
incorporated protectants only, would mean the genetic material that
encodes a pesticidal substance or leads to the production of a
pesticidal substance, has been modified in such a way that the
pesticidal substance produced from the genetic material in the
recipient plant is functionally different than the pesticidal substance
produced in the source. In the 1994 proposal (59 FR at 60524), EPA
explained that in proposing the exemptions the Agency did not intend to
exempt plant-incorporated protectants that are significantly different
in function from the plant-incorporated protectant as it occurs in the
source. EPA believes this limitation would be appropriate because
rearrangements or modifications of the genetic sequence encoding a
pesticidal substance could, for example, result in a plant-incorporated
protectant with significantly different functions from the function 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. 6 and 7).
Such a significantly modified plant-incorporated protectant would not
be eligible for the exemption because it would not 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 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. EPA does
not intend that the concept of functionally modified from the source
would apply to modifications, in the sequence of the genetic material
portion of the plant-incorporated protectant, that may be needed to
achieve correct expression, but which have no significant effect on the
specificity or function of the pesticidal substance.
In order to clearly indicate in the regulatory text that
significantly modified plant-incorporated protectants would not be
covered by this exemption, EPA would include a statement that the
exemption does not apply to a plant-incorporated protectant that has
been functionally modified from the source, and a definition of
functionally modified from the source at Sec. 174.3 as follows:

Functionally modified from the source, when referring to plant-
incorporated protectants only, means the genetic material that
encodes a pesticidal substance or leads to the production of a
pesticidal substance has been modified in such a way that the
pesticidal substance produced from the genetic material in the
recipient plant is functionally different than the pesticidal
substance produced in the source.

The definition of ``bridging crosses between plants'' would
continue to read as follows:

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.

EPA is also considering whether to modify the definition of ``wide
cross'' by including ``protoplast fusion.'' In part, this will depend
on the comment received in response to this proposal (see Unit
III.D.6.), and on whether EPA receives information demonstrating that
novel exposures would be unlikely even with such an expanded
definition.
``Genetic material that encodes for a pesticidal substance'' or
leads to the production of a pesticidal substance does not include
regulatory regions or noncoding, nonexpressed nucleiotide sequences.
ii. FFDCA section 408. To exempt all residues of the pesticidal
substance portion of plant-incorporated protectants derived from plants
sexually compatible with the recipient plant, regardless of the method
by which the plant-incorporated protectant is introduced into the
plant, EPA would substitute the following language at 40 CFR 174.479:

Sec. 174.479 Pesticidal substance from sexually compatible
plant; exemption from the requirement of a tolerance.
Residues of a pesticidal substance that is part of a plant-
incorporated protectant derived from a sexually compatible plant are
exempt from the requirement of a tolerance if all the following
conditions are met:
(a) The genetic material that encodes for the pesticidal
substance or leads to the production of the pesticidal substance is
derived from a plant that is sexually compatible with the recipient
food plant.
(b) The genetic material that encodes for the pesticidal
substance or leads to the production of the pesticidal substance has
never been derived from a source that is not sexually compatible
with the recipient plant.
(c) The active ingredient has not been functionally modified
from the source.
(d) The residues of the pesticidal substance are not present in
food from the plant at levels that are injurious or deleterious to
human health.

[[Page 37860]]

2. Case-by-case review of eligibility for exemption through
notification process. EPA also requests comment on a notification
process that would implement a screening procedure for plant-
incorporated protectants derived through genetic engineering from
plants sexually compatible with the recipient plant.
Under this alternative to registration, as part of the final rule
EPA would establish criteria to determine whether a plant-incorporated
protectant derived through genetic engineering from plants sexually
compatible with the recipient plant is ``substantially equivalent'' to
a plant-incorporated protectant that could have been derived through
conventional breeding from plants sexually compatible with the
recipient plant. Anyone intending to sell or distribute a plant-
incorporated protectant could submit a notification to EPA seeking a
determination that a plant-incorporated protectant qualified for this
exemption, accompanied by an analysis demonstrating that the plant-
incorporated protectant derived through genetic engineering from plants
sexually compatible with the recipient plant is substantially
equivalent to a plant-incorporated protectant derived through
conventional breeding from sexually compatible plants. The Agency would
review the submission and evaluate it against the regulatory criteria
to determine whether the plant-incorporated protectant met the criteria
for an exemption. At the end of this process, the submitter would
receive a letter describing EPA's conclusion. If EPA determines that
the plant-incorporated protectant met the criteria, it would be exempt
from further regulation under FIFRA, except for the adverse effects
reporting requirement at 40 CFR 174.71. However, if EPA determines that
the plant-incorporated protectant is not substantially equivalent to a
plant-incorporated protectant derived through conventional breeding
from sexually compatible plants, a registration would be required prior
to its sale or distribution, as well as, if residues of the plant-
incorporated protectant are in or on food or feed, a tolerance
exemption.
This proposed alternative would be an intermediate measure between
exemption of the plant-incorporated protectant and registration, and
would ensure that those plant-incorporated protectants derived through
genetic engineering from plants sexually compatible with the recipient
plant are as safe as those derived through conventional breeding. It
would allow the Agency to conduct a case-by-case review of these
products to address those endpoints with which the commenters expressed
the greatest concern over the strength of the Agency's factual basis
for exempting the group as a whole. This notification procedure would,
however, impose a lower degree of oversight than the standard
requirements of pesticide registration. For example, such
``substantially equivalent'' plant-incorporated protectants would only
be subject to the adverse effects reporting requirements at 40 CFR
174.71; unlike registered pesticides, manufacturers would not be
required to obtain establishment numbers or submit section 7 production
reports. Moreover, the plant-incorporated protectants would not be
required to bear FIFRA labels. Nor would the Agency envision requiring
the submission of the standard battery of toxicity testing currently
required under 40 CFR part 158; rather, only data relevant to a
determination of substantial equivalence would be required to be
submitted.
Any person who sells or distributes in commerce a plant-
incorporated protectant derived through genetic engineering without
having obtained either a determination of equivalence or a registration
would violate FIFRA section 12(a)(1)(A). Products sold or distributed
in commerce in violation of section 12 are subject to seizure, pursuant
to FIFRA section 13. In addition, any person selling or distributing
such products are subject to the penalties provided in FIFRA section
14.
This option would only exempt a plant-incorporated protectant from
the registration requirements under FIFRA. If the plant-incorporated
protectant was intended to be used in a food plant, resulting in
pesticide chemical residues, a tolerance exemption would need to be
established, prior to the introduction of the food in commerce. Without
a tolerance exemption, any food bearing residues of the plant-
incorporated protectant would be adulterated, pursuant to section
402(a)(2)(B) of FFDCA, and subject to seizure by FDA. An application
for an exemption from the tolerance requirement could be submitted
concomitantly with the submission for exemption from FIFRA registration
requirements.
i. Criteria for determining substantial equivalence. Currently, EPA
believes that the following considerations could be developed into
criteria relevant to determining whether a plant-incorporated
protectant is substantially equivalent to a plant-incorporated
protectant that could have been derived through conventional breeding
from sexually compatible plants.
a. The source of the gene of interest is a plant sexually
compatible with the recipient plant, and the active ingredient has not
been functionally modified from the source.
b. Any pesticidal substance is not present at deleterious or
injurious levels.
c. The plant-incorporated protectant has the same tissue expression
pattern, including levels of expression, observed in varieties of the
recipient plant currently in widespread agricultural use or consumed by
the U.S. population.
d. Any inert ingredient is on the list of approved inert
ingredients at subpart X of 40 CFR part 174.
Prior to adopting criteria in any final rule, EPA would seek the
advice of its SAP on criteria appropriate for evaluating whether a
plant-incorporated protectant derived through genetic engineering from
plants sexually compatible with the recipient plant is substantially
equivalent to a plant-incorporated protectant that could have been
derived through conventional breeding from sexually compatible plants.
ii. Where to submit notification. By mail, written notifications
would be submitted to: Document Processing Desk (7504C), Office of
Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania
Ave., NW., Washington, DC 20460. In person, deliver requests to:
Environmental Protection Agency, Crystal Mall #2, Room 258, Document
Processing Desk, 1921 Jefferson Davis Hwy., Arlington, VA. In order to
expedite processing, the request must be marked ``Attention: Plant-
Incorporated Protectant Notification Review.''
iii. Contents of notification. The notification could include, for
example:
a. Name and address of requester and name, address, e-mail address,
and telephone number of a person who may be contacted for further
information.
b. Data or information relating to a determination that the
specific plant-incorporated protectant and any inert ingredient(s) are
substantially equivalent to a plant-incorporated protectant derived
through conventional breeding from sexually compatible plants. Such
information could include:
A detailed description of the introduced genetic material,
including certification that the organism(s) that is the source of the
genetic material encoding the pesticidal substance is a plant that is
sexually compatible with the recipient plant.
The source of any selectable markers.
The product(s) of the genetic material, and whether and
how the

[[Page 37861]]

products (both active and inert ingredients) are expected to affect
the behavior of the recipient plant.
Information on all regulatory sequences including those
affecting specificity of tissue expression and information on the level
of expression of the structural genes.
Stability of the introduced genetic material.
c. Any other information the requester might consider relevant.
iv. CBI. To assert a claim of confidentiality, the requester would
have to comply with the applicable procedures in 40 CFR 174.9. Section
174.9(a) states that failure to assert a claim of confidentiality at
the time the information is submitted to EPA will be considered a
waiver of confidentiality for the information submitted, and the
information may be made available to the public, subject to section
10(g) of FIFRA, with no further notice to the submitter.
v. EPA review. EPA would review and evaluate notifications as
expeditiously as possible. If the request received by EPA is complete
(e.g., no additional information is required by EPA or submitted by the
requester as supplemental information, or no amendment to the request
made), EPA would complete its evaluation in between 150 and 180 days of
receipt of the request. EPA may require additional information from the
submitter in order to assess the equivalence of the plant-incorporated
protectant derived through genetic engineering to a plant-incorporated
protectant derived through conventional breeding from sexually
compatible plants. Should EPA require additional information or the
requestor submit supplemental information, more than 150 to 180 days
may be required to complete the assessment. At the conclusion of the
review, EPA will supply a letter to the submitter describing the
Agency's evaluation and determination.
The submitter may supplement, amend, or withdraw his or her
notification in writing, without EPA approval, at any time prior to
EPA's determination. The withdrawal of a request shall be without
prejudice to the resubmission of the notification at a later date.

C. Request for Comment on Proposed Alternative Regulatory Approaches

EPA requests comment on the following issues for the proposed
alternatives described in Unit III.B. EPA requests that respondents
comment on the proposed alternative proposals, and include
consideration of the issues described in Unit III.D. in their comments
on Unit III.C.
1. Distinction between proposed approaches. The two proposed
regulatory alternatives distinguish between plant-incorporated
protectants on the basis of the process by which the plant-incorporated
protectant has been introduced into the plant. EPA requests comment on
whether a distinction based on the process of genetic modification is
justified in light of the state of the science, including the specific
questions and risk concerns raised by the comments received in response
to the Agency's 1994 proposal, and briefly described in Unit III.D.
Given the issues described in Unit III.D. with respect to plant-
incorporated protectants derived through genetic engineering from
plants sexually compatible with the recipient plant, are such products
sufficiently analogous to plant-incorporated protectants derived from
conventional breeding that the Agency can rely on the factual basis,
described in companion documents published elsewhere in this issue of
the Federal Register for plant-incorporated protectants derived through
conventional breeding, to support the exemption in the proposed
regulatory alternative described in Unit III.B.1.
2. Notification process. EPA requests comment on the utility of a
notification process for determining whether a plant-incorporated
protectant derived through genetic engineering from plants sexually
compatible with the recipient plant is equivalent to a plant-
incorporated protectant derived through conventional breeding from
sexually compatible plants. EPA is particularly interested in comments
addressing whether this level of regulatory oversight is necessary to
address the potential risks from plant-incorporated protectants derived
through genetic engineering from plants sexually compatible with the
recipient plant, and whether this level of oversight would adequately
address the safety questions surrounding these products. Can the
factual basis, described in companion documents published elsewhere in
this issue of the Federal Register for plant-incorporated protectants
derived through conventional breeding, be used on a case-by-case basis
to support exemption in the proposed regulatory alternative described
in Unit III.B.2.
EPA requests comment on the criteria described in Unit III.B.2.i.
for evaluating ``substantial equivalence.'' For example, EPA requests
comment on whether reliance on plants currently in widespread
agricultural use, or consumed by the U.S. population is an appropriate
standard, or whether it would be more appropriate to compare the
resulting plant-incorporated protectant to its parental organisms. The
Agency would welcome any information or data that might be of
assistance in developing proposed criteria for use in its potential
notification process. EPA would particularly welcome comment on whether
the criteria described in Unit III.B.2.i., would capture all of the
potential pleiotropic effects of concern with respect to this subgroup
of plant-incorporated protectants. In light of the fact that FDA is
proposing to review all genetically engineered foods for possible
effects resulting from the point of insertion, EPA requests comment on
whether there is any need for EPA to also examine this endpoint. The
Agency is concerned that the final criteria not prevent it from
examining all possible parameters of interest, but also recognizes the
need for determinate criteria for this option to function effectively.
EPA requests comment on whether the potential information needs
described in Unit III.B.2.iii. are adequate for demonstrating
substantial equivalence with plant-incorporated protectants derived
through conventional breeding from sexually compatible plants. EPA
solicits comment on whether there are any additional types of
information that might be useful for demonstrating substantial
equivalence.
3. Variant of notification process for broader group of plant-
incorporated protectants. Some components in plants are widely
distributed across the plant kingdom and thus may be found in many
plant populations, some of which are not sexually compatible with each
other. EPA requests comment on whether a notification process similar
to one described in Unit III.B.2. could be developed for plant-
incorporated protectants from outside the gene pool of the recipient
plant, but nonetheless equivalent to those that evolved within the gene
pool of the recipient plant.
EPA notes that to develop a notification process for such plant-
incorporated protectants, EPA must first develop criteria to describe
such plant-incorporated protectants. EPA would seek the advice of its
SAP in developing proposed criteria. Some of the factors EPA might ask
the SAP to consider in developing criteria for proteinaceous substances
include amino acid sequence homology, post-translational processing,
structure, stability, receptor/ligand specificity, substrate
specificity and equivalence of reaction products. For non-proteinaceous
plant-incorporated protectants, the chemical composition

[[Page 37862]]

and structure of the introduced plant-incorporated protectant could be
compared with the plant-incorporated protectants that are normally
components of the recipient plant. This information on composition and
structure could then be related to the function of the introduced
plant-incorporated protectant. Other factors that might also be
considered in this determination include:
i. When during the plant's life cycle the pesticidal substance is
produced.
ii. In which part of the plant (e.g., leaves, roots, fruit) the
pesticidal substance is produced.
iii. The levels at which it is produced.
EPA would welcome any information or data that might be of assistance
in developing proposed criteria for use in this variant of a potential
notification process.

D. Request for Comment on Risk Issues

Several risk issues have been raised for plant-incorporated
protectants derived through genetic engineering from plants sexually
compatible with the recipient plant. EPA requests comment on these
issues, described in this unit, in the context of the two proposed
alternative regulatory approaches described in Unit III.B.
1. Levels of toxicants? Some comments described toxic substances
naturally occurring in plants in sexually compatible populations, and
expressed concern that EPA's 1994 proposal to exempt all plant-
incorporated protectants derived from sexually compatible plants did
not include consideration of the potential for risk associated with
increases in levels of such substances. These comments implied that
such increases are more likely to occur with plant-incorporated
protectants derived through genetic engineering from sexually
compatible plants. One commenter stated, for example, that use of
``artificial regulators (regardless of source) may allow genes to
escape natural dampening mechanisms and to be produced at extremely
high levels not found in naturally occurring or traditionally bred
plants. Artificial promotors may also result in toxins being produced
in tissues where they are not ordinarily produced, or in some cases in
every cell of the plant'' (Ref. 8). Another commenter stated that ``EPA
appears to be ignoring a basic axiom of toxicology, e.g., the dose
makes the poison'' (Ref. 5).
In a companion document published elsewhere in this issue of the
Federal Register, EPA, recognizing that increases in levels of
toxicants can occur in conventional breeding as well as in varieties
developed through genetic engineering, imposed a condition on the
exemption at 40 CFR 174.479 to address this concern. In order to allow
EPA and FDA to act expeditiously, should a rare instance of levels high
enough to render food injurious or deleterious occur, residues of the
pesticidal substances derived through conventional breeding from
sexually compatible plants qualify for exemption from the tolerance
requirement only if the ``residues of the pesticidal substance are not
present in food from the plant at levels that are injurious or
deleterious to human health.''
EPA requests comment on whether, in the context of food and FFDCA
section 408 requirements, such a limitation is sufficient to address
the same concern for residues of pesticidal substances derived through
genetic engineering from plants sexually compatible with the recipient
plant, should EPA exempt this later subgroup, as described in Unit
III.B.1.
EPA also requests comment on whether, in the context of FIFRA
requirements, this condition would be sufficient to address the
concerns that have been raised with respect to potential effects on
nontarget organisms for plant-incorporated protectants derived through
genetic engineering from plants sexually compatible with the recipient
plant.
EPA requests comment on whether such a limitation is meaningful for
those plant-incorporated protectants not in plants used for food or
feed (e.g., trees), given that deleterious or injurious substances in
such semi-managed plants naturally tend to greater ranges of expression
than seen in crop plants, including higher ranges of expression (Ref.
9).
Commenters also discussed the potential for changes in promotors or
other regulatory elements to affect tissue specific expression of
toxicants, i.e., where previously a toxicant was expressed only in
trace amounts in the edible part of the plant, a new promotor might
result in high levels of expression in the edible part. EPA requests
comment on whether such events are more likely to occur with plants-
incorporated protectants derived through genetic engineering than with
those derived through conventional breeding from sexually compatible
plants. EPA also requests comment on whether the condition placed on
the tolerance exemption at 40 CFR 174.479, that the ``residues of the
pesticidal substance are not present in food from the plant at levels
that are injurious or deleterious to human health'' are adequate to
address this concern for plant-incorporated protectants derived through
genetic engineering from plants sexually compatible with the recipient
plant in the context of FFDCA section 408. Is this condition sufficient
to address the concern for FIFRA?
2. Potential for production of a novel toxicant? In developing the
final rule published elsewhere in this issue of the Federal Register in
companion documents, EPA also considered the possibility that
expression of a transgenic protein could result in the plant producing
a toxicant not observed in either of the parent species. An example of
this would be the case of somatic hybrids between Solanum brevidans and
S. tuberosum producing the toxicant, demissine, not found in either
parental line. Laurila et al. (Ref. 10) advanced the hypothesis that
the hydrogenase enzyme of S. brevidans produced the toxicant by
hydrogenating solanine, a compound that is found in S. tuberosum but
not in S. brevidans. Portions of the metabolic pathways necessary to
produce this substance apparently existed in the parental species, and
the mingling of the genetic material resulted in a complete pathway for
production of demissine. This example suggests that novel metabolic
pathways could be created in a plant through the introduction of a
single gene, should other components of the pathway already be present
in the plant. EPA requests comment on whether there is any difference
in the probability of this occurring in plants in sexually compatible
populations into which the plant-incorporated protectant was introduced
by genetic engineering as compared to conventional breeding.
3. Consequences of transfer of ability to produce higher levels of
a plant-incorporated protectant to wild or weedy relatives? EPA also
received comments on the potential for a food crop or other commercial
plant engineered to produce unusually high levels of a plant-
incorporated protectants to ``interbreed with a wild, weedy relative
which in turn would become very resistant to certain insect pests. The
wild relative, now free from certain pest damage, could increase in
number and either become a much worse pest itself or disrupt an
ecosystem. . .'' (Ref. 5). Gene flow from crop plants to wild relatives
has been observed in plants developed through conventional breeding in
sexually compatible populations (Refs. 11 and 12). It has not yet been
established whether gene flow into feral populations, from either
genetic engineered or conventionally bred plants, can endow wild
relative

[[Page 37863]]

populations with a selective advantage that might enhance their
potential for weediness.
Given that wild relatives of crop plants are likely to already
possess traits similar to those in related crop plants, and express
these traits at a higher range of levels than crop plants, what is the
probability that outcrossing of the ability to express such traits at
high levels from crop plants to wild or weedy relatives, would give the
wild relatives a competitive advantage?
EPA also requests comment on whether this phenomenon could result
in significantly different consequences when comparing gene flow
between plant-incorporated protectants derived through genetic
engineering from sexually compatible plants as compared to plant-
incorporated protectants derived through conventional breeding from
sexually compatible plants.
4. Does use of antibiotic or herbicide resistance or other
selectable markers present risk? Because genetic engineering techniques
are so precise, a gene can be excised from the source organism without
unwanted, extraneous genetic material. The precise gene can then be
introduced into the recipient organism. However, there can be other
genetic information on the construct used to introduce the desired
gene, and although this genetic information may also be precise, it may
not be part of the gene pool of the recipient plant, e.g., genes for
herbicide resistance used as a selectable marker. In a companion
document published elsewhere in this issue of the Federal Register, EPA
describes its determination that the Agency will adopt the definition
of inert ingredient it proposed in 1994. An inert ingredient for plant-
incorporated protectants is ``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 that genetic material is intentionally introduced
into a living plant in addition to the active ingredient.'' In that
same companion document, EPA also describes the qualification that a
plant-incorporated protectant can only be exempt if the inert
ingredient(s) used with an exempt active ingredient is on the list of
approved inert ingredients at subpart X of 40 CFR part 174.
EPA anticipates that a plant-incorporated protectant qualifying for
exemption under the proposed regulatory alternative described in Unit
III.B.1. would be composed of an active ingredient derived through
genetic engineering from a plant sexually compatible with the recipient
plant and an ingredient on the approved list at subpart X of 40 CFR
part 174. In light of this assumption, and given that the inserted
structural gene of interest (for EPA's purposes, the gene encoding the
pesticidal substance) is taken from the same gene pool in which it
normally exists, EPA requests comment on whether, even if the
structural gene of interest in the inert ingredient is derived from a
source not sexually compatible with the recipient plant, the plant-
incorporated protectant can still be considered to be ``substantially
equivalent'' to a plant-incorporated protectant that could have been
derived through conventional breeding. Specifically, EPA requests
comment on whether the risks associated with such plant-incorporated
protectants derived through genetic engineering are any greater that
the risks associated with plant-incorporated protectants derived
through conventional breeding.
5. Should protoplast fusion be included in the definition of wide
cross? EPA requests comment on whether protoplast fusion should be
added to the definition of wide crosses. In the official comment period
for the November 23, 1994 Federal Register, EPA received one comment
that suggested protoplast fusion should be included among the
techniques listed in the definition of wide crosses between plants. A
protoplast is 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 from two different plants are fused together, producing a
hybrid somatic cell with a genetic makeup resulting from the
combination and sorting of the two plant genomes. The hybrid somatic
cell is grown on specialized media into a mature plant. In support of
the request, the commenter argued that the hybridization of somatic
cells (i.e., protoplast fusion) has a history of use to artificially
induce sexual compatibility. For the most part, the more closely
related the plants donating the protoplasts used for the fusion, the
more likely a viable hybrid will be obtained. Currently, in a companion
document published elsewhere in this issue of the Federal Register, EPA
specifically excludes cell fusion from the definition of conventional
breeding, with cell fusion defined as ``the fusion in vitro of two or
more cells or protoplasts.''
EPA requests comment on whether protoplast (or cell) fusion, or
alternatively, some subgroup of fusions (e.g., intraspecific or
intrageneric), should be included in the definition of wide crosses in
light of the following dietary and environmental considerations. First,
in the example provided in Unit III.D.2. describing the potential for
creation of new toxicants, dimissine arose through the fusion of
protoplasts of S. tuberosum and S. brevidans. Second, the FDA in its
1992 ``Statement of Policy: Foods Derived from New Plant Varieties''
(57 FR 22984, May 29, 1992) expresses a concern that protoplast fusion
might confer on food from the host plant the allergenic properties of
food from the donor plant.

IV. Notice of Data Availability and Request for Comment

In April 2000, the NAS released a report entitled ``Genetically
Modified Pest-Protected Plants: Science and Regulation'' (Ref. 13).
Prepared by an expert committee, this report examined the proposals
offered by EPA in the November 23, 1994, Federal Register (59 FR
60496). This report recommended that EPA reconsider the Agency's
proposed exemptions, raising a number of questions, primarily with
respect the Agency's factual support for the exemptions. EPA requests
comment on the information, analyses, and conclusions contained in the
NAS report only with respect to those portions of its original
proposals that remain pending. EPA is not soliciting comments on any
issues beyond those raised specifically by the information contained in
the NAS report; for example, the NAS report raised no issues with
respect to the Agency's analyses of the human health risks associated
with viral coat proteins. Any comments submitted on such issues will be
treated as having been submitted after the close of the comment period,
as the Agency has twice solicited comment on these issues, in 1994 and
1997.
The NAS report presents a number of competing considerations
without necessarily providing the Agency with a ready basis for
resolving these issues. For example, the report (Ref. 13 at 44-46)
states:

The 1987 NAS report noted that the risks associated with rDNA-
engineered organisms are ``the same in kind'' as those associated
with unmodified organisms and organisms modified by other methods.
The committee agrees with that statement for pest-protected plants
in that both transgenic and conventional plants may pose certain
risks and the resulting plant phenotypes are often similar.
Transgenic breeding techniques can be used to obtain the same
resistance

[[Page 37864]]

phenotype as conventional methods (for example resistance to
microbial pathogens, nematodes, and insects). Because both methods
have the potential to produce organisms of high or low risk, the
committee agrees that the properties of a genetically modified
organism should be the focus of risk assessments, not the process by
which it was produced (point 3).
In this regard, the committee found that:
There is no strict dichotomy between or new categories of the
health and environmental risks that might be posed by transgenic and
conventional pest-protected plants.
The committee recognizes that the magnitude of the risk varies
on a product by product basis. The committee also agrees with points
1 and 2 in the sense that the potential hazards and risks associated
with the organisms produced by conventional and transgenic methods
fall into the same general categories. As this report discusses,
toxicity, allergenicity, effects of gene flow, development of
resistant pests, and effects on non-target species are concerns for
both conventional and transgenic pest-protected plants.
The committee agrees with the 1987 NAS principles in that the
magnitude of quantitative risk does not depend on the genetic-
modification process. It depends on the new genes that are expressed
in the plant. End points of risk (such as illness in humans and
declines in nontarget species) can be the same regardless of whether
a specific new gene was transferred by conventional or transgenic
methods. For example, if the same alkaloid gene is transferred by
sexual hybridization or Agrobacterium-mediated insertion, the risk
should be similar. If a gene coding for a novel trait is transferred
by transgenic methods, but cannot be transferred by conventional
methods, it is the expressed trait that requires scrutiny, not the
method of transfer.

Yet by contrast, on page 128, the report states:

The committee recognizes the realistic limitations of overseeing
the pesticidal substances in conventional pest-protected plants and,
given their history of safe use, recognizes that there are practical
reasons for exempting those substances. However, the committee
questions the scientific basis used by EPA for this exemption
because no strict dichotomy or new categories appear to exist
between the risks to health and the environment that might be posed
by conventional and transgenic pest-protected plant products
(section 2.2.1).
The categorical exemption also applies to transgenic pest-
protected plant products that contain transgenes from sexually
compatible species, and the committee questions the scientific basis
for this exemption as well, specifically because the genes and gene
products can be expressed at concentrations far greater than the
concentrations at which they are naturally expressed (sections 2.4.1
and 2.5.2). Even though the risks of many transgenic pest-protected
plants containing genes from sexually compatible species are
expected to be low and would justify exemption, lack of experience
with these products and public concern over genetic engineering
suggest that a blanket exemption for them is inadvisable.

EPA requests comment on how to best reconcile these competing
considerations.

V. Proposed Alternative Regulatory Approaches to Plant-Incorporated
Protectants Based on Viral Coat Proteins

This Unit solicits additional comment on the two alternative
regulatory approaches the Agency discussed in greater detail in the
1994 proposal (59 FR 60496, e.g., see 60525 through 60528). EPA
solicits additional public comment on these alternatives in light of
the issues raised by the NAS report, as well as on the issues raised by
commenters on the 1994 proposal. The Agency intends to consider public
comments and make final determinations to complete these other
rulemakings within 9 to 12 months after the close of the comment period
for the supplemental proposal, which is currently set at 30 days. Until
the Agency takes a final action on these other exemptions, the Agency
intends to maintain its current practices on regulation of plant-
incorporated protectants.

A. History

Coat proteins are those substances that viruses produce to
encapsulate and protect the nucleic acids comprising their genetic
material. When the genetic material encoding the information for making
the coat protein of a plant virus is introduced into a plant's genome,
the plant becomes resistant to infection by the virus donating the
genetic material for the coat protein (and frequently to viruses
closely related to the donor virus) (Refs. 14 and 15). This resistance
is termed viral coat protein mediated-resistance or vcp-mediated
resistance (Refs. 14 and 15). Coat proteins from plant viruses intended
to be produced and used in living plants for vcp-mediated resistance to
viral disease, along with the genetic material necessary to produce the
coat proteins, are plant-incorporated protectants.
1. 1994 Proposal. In the 1994 proposal, EPA proposed to exempt from
all FIFRA requirements, except for the adverse effects reporting
requirement at Sec. 174.71, all plant-incorporated protectants based on
coat proteins from plant viruses (Option 1) (59 FR at 60525). EPA also
described an alternative option (Option 2) offering a more limited
exemption (59 FR 60526). Under this alternative option, the exemption
would be limited to those plant-incorporated protectants based on coat
proteins from plant viruses that would have the least potential to
confer selective advantage on free-living wild plant relatives of the
plants containing these plant-incorporated protectants. Under Option 2,
a coat protein would be exempt if:

The pesticidal substance is a coat protein from a plant virus
and the genetic material necessary to produce the coat protein has
been introduced into a plant's genome, and the plant has at least
one of the following characteristics:
(1) The plant has no wild relatives in the United States with
which it can successfully exchange genetic material, i.e., corn,
tomato, potato, soybean, or any other plant species that EPA has
determined has no sexually compatible wild relatives in the United
States.
(2) It has been demonstrated to EPA that the plant is incapable
of successful genetic exchange with any existing wild relatives
(e.g., through male sterility, self-pollination).
(3) If the plant can successfully exchange genetic material with
wild relatives, it has been empirically demonstrated to EPA that
existing wild relatives are resistant or tolerant to the virus from
which the coat protein is derived or that no selective pressure is
exerted by the virus in natural populations.

2. Public comments. In response to its November 23, 1994 Federal
Register request for comment on the proposal to exempt plant-
incorporated protectants based on the coat proteins of plant viruses,
EPA received 65 comments. Many of the comments supported Option 1. Some
of the comments supported adoption of Option 2. In the opinion of these
commenters, Option 2 appropriately addresses concerns about the
potential effects of outcrossing of plant-incorporated protectants
based on coat proteins from plant viruses from crop plants to wild or
weedy relatives. These comments pointed out that there is scientific
evidence indicating that crops may transfer traits to wild relatives,
and that many crops grown in the United States have wild relatives that
are either native or have been introduced. These comments questioned
the adequacy of available data to evaluate the probability that
outcrossing of plant-incorporated protectants based on coat proteins
from plant viruses could confer a selective advantage on wild or weedy
relatives of crop plants. Approximately one-third of the comments
opposed the exemption of plant-incorporated protectants based on coat
proteins from plant viruses. Most of these comments offered no
explanation for their opposition. Those who explained their opposition
cited among their concerns, a potential for creation of more aggressive
weeds and disturbance to centers of diversity

[[Page 37865]]

3. Current status. The Agency received scientific information both
from commenters supporting Option 1 and commenters supporting Option 2.
In this supplemental document, EPA requests additional public comment
on the proposed alternative approaches discussed in the 1994 Federal
Register and the risk considerations associated with weediness raised
in comment. EPA will consider all comments received on this proposal,
including comments received in response to the original proposal in
1994, and any comments received in response to this supplemental
document, in arriving at a decision on how to proceed.

B. Description of Proposed Modification to Language of Proposed
Exemption

Were EPA to implement either of the two options proposed in 1994,
it would modify the language to clearly state that plant-incorporated
protectants that are significantly different in structure or function
from the plant-incorporated protectant as it occurs in the source would
not be exempt.
In the 1994 proposal (59 FR at 60524), EPA explained that the
Agency did not intend to exempt plant-incorporated protectants that are
significantly different in structure or function from the plant-
incorporated protectant as it occurs in the source. EPA believes this
limitation is appropriate for coat proteins from plant viruses because
rearrangements or modifications of the genetic sequence encoding a
pesticidal substance could, for example, result in a plant-incorporated
protectant with significantly different functions from the function 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. 6 and 7).
Such a significantly modified plant-incorporated protectant would not
be eligible for the exemption. It 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.
Should EPA implement either Option 1 or Option 2, the Agency would
include a statement that the exemption does not apply to a plant-
incorporated protectant functionally modified from the source.

C. Request for Comment

The NAS report recommends that the:

EPA should not categorically exempt viral coat proteins from
regulation under FIFRA. Rather, EPA should adopt an approach, such
as the Agency's alternative proposal. . ., that allows the agency to
consider the gene transfer risks associated with the introduction of
viral coat proteins to plants. (Ref. 13 at 132)

The NAS bases its recommendation primarily on a lack of information on
the effects of the transfer of genes conferring pest resistance from
crop plants to weedy or wild relatives.
EPA solicits any additional information that might assist the
Agency in determining whether it should implement Option 1, i.e.,
exempt all plant-incorporated protectants based on viral coat proteins,
or Option 2, i.e., an approach that allows the Agency to evaluate the
gene transfer risks associated with the introduction of viral coat
proteins to each candidate plant. In addition, in light of the fact
that USDA reviews potential plant-pest related issues relative to viral
coat proteins, EPA requests comment on whether there is any need for
EPA to also examine this endpoint.
EPA solicits comment on whether outcrossing of plant-incorporated
protectants based on coat proteins from plant viruses could confer a
selective advantage on wild or weedy relatives of crop plants, and if
so, which crop plants. EPA would be particularly interested in
receiving data on this issue.
EPA specifically requests comment on whether acquired virus-
resistance could, for example: (1) Allow a wild plant to increase its
range or population density; and/or (2) permit a plant's population
density to increase so that the plant dominates a community where it
was far less common before acquisition of the trait.
As a condition of the exemption, EPA could require applicants for
the exemption to submit studies or generate data on the gene transfer
risks associated with the candidate plant-incorporated protectant.
Alternatively, EPA could require some degree of monitoring beyond that
which would be required by the adverse effects reporting requirement.
EPA requests comment on whether either of these approaches is necessary
to address the concerns raised by the NAS and the commenters, or
whether sufficient data currently exists to evaluate the gene transfer
risks presented by the class of products that would be covered under
either Option 1 or 2.

VI. Proposal on Plant-Incorporated Protectants that Act Primarily
by Affecting the Plant

In this Unit, EPA solicits additional public comment on this
proposed exemption and on the scientific issues raised by the NAS
report (Ref. 13) and in comments received on the 1994 proposal. The
Agency intends to consider public comments and make final
determinations to complete these other rulemakings within 9 to 12
months after the close of the comment period for the supplemental
proposal, which is currently set at 30 days. Until the Agency takes a
final action on these other exemptions, the Agency intends to maintain
its current practices on regulation of plant-incorporated protectants.

A. History

In the 1994 proposal (59 FR at 60525), EPA stated that one of the
Agency's primary goals in regulating pesticides is to control the
potential for adverse effects of pesticides on nontarget organisms. EPA
reasoned that an important component in the evaluation of this
potential is the way in which the pesticidal substance acts on the
target pest since it would also likely affect nontarget organisms
through the same mechanism. EPA further reasoned that some plant-
incorporated protectants could act through mechanisms that are less
likely to be directly toxic. The Agency stated a belief that although
it is possible for these substances to adversely affect nontarget
organisms, in most cases, they would pose significantly lower levels of
environmental risk than plant-incorporated protectants with a
generalized toxic mechanism of action. EPA identified those plant-
incorporated protectants it thought would act in this manner as those
that act primarily by affecting the plant so that the pest is inhibited
from attaching to the plant, penetrating the plant's surface, or
invading the plant's tissue.
1. 1994 Proposal. In the November 23, 1994 Federal Register, EPA
proposed to exempt from all FIFRA requirements, except for the adverse
effects reporting requirement at 40 CFR 174.71, plant-incorporated
protectants that act primarily by affecting the plant. The proposed
regulatory text presented criteria to define mechanisms of action that
exert the pesticidal action primarily by affecting the plant. The
proposed language reads as follows:

The pesticidal substance acts primarily by affecting the plant
so that the target pest is inhibited from attaching to the plant,
penetrating the plant, or invading the plant's tissue in at least
one of the following ways:
(i) The pesticidal substance acts as a barrier to attachment of
the pest to the host plant, a structural barrier to penetration of
the pest into the host plant, or a structural barrier to spread of
the pest in the host plant, for example, through the production of
wax or lignin, or length of trichomes (plant hairs).

[[Page 37866]]

(ii) The pesticidal substance acts in the host plant to
inactivate or resist toxins or other disease-causing substances
produced by the target pest.
(iii) The pesticidal substance acts by creating a deficiency of
a plant nutrient or chemical component essential for pest growth on/
in the host plant.

In the 1994 Federal Register document, EPA also indicated that it
was considering extending this exemption to include substances such as
plant hormones, because plant hormones act within the plant to
``primarily affect the plant'' and do not act directly on a target pest
(59 FR at 60525, 60531). EPA requested public comment on whether plant
hormones should be included in the exemption for plant-incorporated
protectants that act primarily by affecting the plant.
2. Public comments. EPA received 23 comments that addressed this
proposed exemption. A majority of comments supported the exemption of
plant-incorporated protectants that act primarily by affecting the
plant. The comments opposing the exemption primarily expressed concern
about the potential for outcrossing of the trait from crop plants to
wild relatives to increase weediness in the wild relatives. These
concerns were variously described as concerns that outcrossing of these
plant-incorporated protectants to wild relatives might result in the
following outcomes: First, produce hardier plants that become weeds in
agro-ecosystems; second, produce hardier plants that displace less
hardy types; or, third, adversely impact nontarget organisms that
depend for their survival on interactions with wild plants. Some
comments urged EPA, in order to address the concerns, to adopt an
approach that would subject a plant-incorporated protectant to
regulation based on whether the plant-incorporated protectant was
introduced into the recipient plant through use of rDNA or other
techniques of modern biotechnology.
Fourteen comments responded to EPA's request for comment on whether
to exempt plant hormones because they act primarily by affecting the
plant. Most comments favored the exemption of plant hormones, stating
that plant hormones act within the plant to affect the plant's behavior
and do not have a toxic mode of action. A few comments favored
exemption of plant hormones except when there is clear indication of
unreasonable adverse effects to the plants as can occur in some plant
diseases mediated by microorganisms. The comments disagreeing with the
exemption expressed concern that outcrossing of plant hormones from
crop plants to wild relatives might confer competitive advantage on the
wild relatives.
3. Current status. In this supplemental document, EPA requests
additional public comment on this proposed exemption and several risk
issues raised in comment. EPA will consider all comments received on
this proposal in arriving at a determination, including comments
received in response to the original proposal in 1994, and any comments
in response to this supplemental document.

B. Proposed Modification to Language of Proposed Exemption

The Agency is considering whether to modify the language of the
proposed exemption as follows:
1. Hypersensitive response. Some comments suggested the
hypersensitive response in plants would fall within the definition of a
plant-incorporated protectant that functions by primarily affecting the
plant. EPA understands the hypersensitive response to involve compounds
that initiate, potentiate, or enhance hypersensitive or hypersensitive-
type responses that result in area-specific necrosis in response to
microbial invasion of plant tissue, thus limiting spread of the
pathogen within the plant. EPA believes that the criteria of this
exemption as proposed in 1994 would include substances involved in the
hypersensitive response. EPA requests comment on whether, for
regulatory clarity, the Agency should add language to the regulatory
text at 40 CFR part 174 to clearly show that substances involved in
hypersensitive or hypersensitive-type responses are exempt. That
language would read as follows:

(iv) By initiating, potentiating, or enhancing hypersensitive or
hypersensitive-type responses that, in response to invasion by a
phytopathogen, results in necrosis of specific areas of plant tissue
thereby limiting the spread of the pathogen in or on the plant.

2. Functionally modified from the source. As described in Unit
V.B., in proposing the exemptions the Agency did not intend to exempt
plant-incorporated protectants that are significantly different in
structure or function from the plant-incorporated protectant as it
occurs in the source (59 FR at 60524). The discussion at Unit III.B.i.
and Unit V.B., applies equally to this proposed exemption for plant-
incorporated protectants that act primarily by affecting the plant. In
order to clearly indicate in the regulatory text that significantly
modified plant-incorporated protectants would not be covered by this
exemption, EPA would include a statement in this exemption that it does
not apply to a plant-incorporated protectant that has been functionally
modified from the source.
To this end, the following language would be added to the proposed
exemption:

A plant-incorporated protectant acts primarily by affecting the
plant if the plant-incorporated protectant has not been functionally
modified from the source and the pesticidal substance:
(1) . . . .

The proposed definition of ``functionally modified from the
source'' as described at Unit III.B.i., would also apply to this
proposed language.
3. Plant hormones. Plant hormones are substances produced by plants
that play a major role in the regulation of plant growth by either
accelerating or retarding, through physiological action, the rate of
growth or rate of maturation of the plant, or the produce thereof (Ref.
16). Known classes of plant hormones occurring naturally in plants are
auxins, cytokinins, ethylene, abscisic acid, and gibberellins. Plant
hormones are active in the living plant in very small quantities.
Were EPA to add specific language to this proposed exemption
indicating that plant hormones act primarily by affecting the plant,
the Agency would also add a definition of plant hormone in the context
of plant-incorporated protectants at Sec. 174.3 as follows:

Plant hormone, when referring to plant-incorporated protectants
only, would mean naturally occurring auxins, cytokinins, ethylene,
abscisic acid, and gibberellins, produced and used in a living
plant, or in the produce thereof.

C. Request for Comment

1. Hypersensitive response. EPA solicits comment on whether the
substances involved in the hypersensitive response meet the proposed
criteria and act primarily by affecting the plant. EPA requests comment
on whether the language it proposes in this supplemental document
adequately describes substances involved in the hypersensitive
response.
2. Functionally modified from the source. EPA solicits comment on
whether the language it has proposed adequately addresses its concern
that the genetic material not be functionally modified from the source.
EPA solicits comment on whether this language effectively ensures that
the genetic material may not be so modified that it has a significantly
different specificity or function in the recipient plant than it did in
the source plant, yet permits modifications that may be needed to

[[Page 37867]]

achieve correct expression, but which have no significant effect on the
specificity or function of the pesticidal substance.
3. Plant hormones. EPA solicits comment on whether the proposed
definition of plant hormone appropriately describes this group of plant
substances, and whether these substances act primarily by affecting the
plant.
EPA solicits comment on whether plant hormones present a low
probability of risk, particularly in light of the NAS report statement
that plant hormones ``often cause multiple changes in plants, including
changes in secondary metabolites that might be toxic'' (Ref. 13 at
133).
EPA also specifically solicits comment on the NAS statement that
``there is a need to consider separately the impact of plant hormones
on nontarget species and the potential for the genes that code for
these substances to move to feral populations of weedy relatives of the
crop, where they could increase recipient plants' fitness'' (Ref. 13 at
133). In light of this NAS statement, EPA specifically solicits
information supporting the broad exemption that EPA proposed in 1994
for plant-incorporated protectants that act by primarily affecting the
plant. EPA also requests comment on whether there are subgroups within
this category of plant-incorporated protectants for which information
exists supporting a finding that the products present a low probability
of risk. Commenters are encouraged to submit such information to the
Agency.
EPA also solicits comment on the comment received in response to
the 1994 proposal that favored exemption of plant hormones except when
there is clear indication of unreasonable adverse effects to the plants
as can occur in some plant diseases mediated by microorganisms (Ref.
17, for example). The Agency cannot determine the direct relevance that
these pathogenic effects would have to this specific exemption, and
requests additional information.
4. Are there subgroups of this category meeting the FFDCA section
408(c) exemption standard? A plant-incorporated protectant in or on
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 or on food. If
a plant-incorporated protectant is not used in a crop used as food
(e.g., the plant-incorporated protectant is produced and used in an
ornamental plant), the FFDCA section 408 requirements do not need to be
considered when determining whether the plant-incorporated protectant
can be exempted from FIFRA requirements. However, if a plant-
incorporated protectant is used in a crop used as food (e.g., the
plant-incorporated protectant is produced and used in corn), the FFDCA
section 408 requirements must be considered when determining whether
the plant-incorporated protectant can be exempted from FIFRA
requirements. To be considered for full exemption from FIFRA
requirements, exemptions from the FFDCA requirement of a tolerance must
exist for all of the residues. (See Unit VII.D.1.iv. of the companion
document published elsewhere in this issue of the Federal Register on
regulations for plant-incorporated protectants under FIFRA for
additional details).
When EPA proposed in 1994 to exempt from FIFRA requirements plant-
incorporated protectants that act primarily by affecting the plant, it
did not, because of the broad range and variety of plant-incorporated
protectants comprising this category, propose a companion proposal
exempting residues of the substance portion of plant-incorporated
protectants in this category from the FFDCA section 408 requirement of
a tolerance. The Agency would also be interested in comments that
describe subgroups of plant-incorporated protectants in this category
that would meet the FFDCA section 408(c) standard for an exemption. EPA
will treat such comments as a petition for a tolerance exemption
pursuant to FFDCA section 408(d); commenters therefore are encouraged
to review sections 408(b)(2), (c) and (d) in preparing their comments.

VII. Documents in the Official Record

As indicated in Unit I.B.2., the official record for this
supplemental proposal has been established under docket control number
OPP-300370B, 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 supplemental proposal and were cited in this document by the
number indicated:
1. USDA/APHIS. 1987. Plant pests; Introduction of genetically
engineered organisms or products; Final rule. (52 FR 22891, June 16,
1987).
2. USDA/APHIS. 1993. Genetically engineered organisms and products;
Notification procedures for the introduction of certain regulated
articles; and petition for nonregulated status; Final rule. (58 FR
17044, March 31, 1993).
3. USDA/APHIS. 1997. Genetically engineered organisms and products;
Simplification of requirements and procedures for genetically
engineered organisms. (62 FR 23945, May 2, 1997).
4. 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.
5. Hansen, M. and J. Halloran. In a letter dated February 22, 1995
on docket numbers OPP-300367 through 300371.
6. International Food Biotechnology Council. 1990. Biotechnologies
and food; Assuring the safety of foods produced by genetic
modification. Regulatory Toxicology and Pharmacology. Vol. 12. Academic
Press. New York, New York.
7. 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. 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.
8. Rissler, J. and M. Mellon. In a letter dated January 23, 1995,
on docket control numbers OPP-300367 through OPP-300371.
9. EPA issue paper. 1994. FIFRA: Benefit and environmental risk
considerations for inherent plant-pesticides.
10. Laurila, J., I. Lasko, J. P. T. Valkonen, R. Hiltunen, and E.
Pehu. 1996. Formation of parental type and novel glycoalkaloids in
somatic hybrids between Solanum brevidans and S. tuberosum. Plant
Science. 118:145-155.
11. Linder, C. R. Long-Term Introgression of Crop Genes into Wild
Sunflower Populations. Theoretical Applied Genetics. 87:339-347. 1998.
12. Goldburg, R. In a letter dated February 6, 1995, on docket
control number OPP-300370.
13. National Research Council. 2000. Genetically Modified Pest-
Protected Plants: Science and Regulation. (Prepublication copy).
National Academy Press. Washington DC.
14. Cook, R. J. and C. O. Qualset. 1996. (Eds) Appropriate
oversight for plants with inherited traits for resistance to pests.
Institute of Food Technologists. info@ift.org.
15. EPA. 2000. Economic analysis of the plant-incorporated
protectant regulations under the Federal

[[Page 37868]]

Insecticide, Fungicide, and Rodenticide Act.
16. EPA. 2000. Summary of public comments and EPA response on
issues associated with plant-incorporated protectants for dockets
listed in OPP-300368, OPP-300368A, OPP-300369, OPP-300369A, OPP-300370,
OPP-300370A, OPP-300371, and OPP-300371A.

B. Additional Information

The following additional sources of information are included in the
complete official record for this rulemaking:
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 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-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-300369B for
the document entitled ``Regulations Under the Federal Insecticide,
Fungicide, and Rodenticide Act for Plant-Incorporated Protectants
(Formerly Plant-Pesticides)'' (FRL-6057-7) published elsewhere in this
issue of the Federal Register.
The docket identified by the docket control number OPP-300370B for
this document (FRL-6760-4).
Also included in the complete official record for this document
are:
1. Public comments submitted in response to the proposals and
supplemental documents cited in the Unit III.B. In addition, comments
received subsequent to the close of the comment period for the 1994
proposal have been included in the record for this supplemental
proposal. This includes a report entitled ``Appropriate Oversight for
Plants with Inherited Traits for Resistance to Pests'' (Ref. 14), as
well as the NAS report (Ref. 13).
2. Reports of all meetings of the Biotechnology Science Advisory
Committee and the FIFRA Science Advisory Panel pertaining to the
development of the final rule for plant-incorporated protectants
published in companion documents elsewhere in this issue of the Federal
Register.
3. The Economic Analysis of the final rule for plant-incorporated
protectants published in companion documents elsewhere in this issue of
the Federal Register (Ref. 15) and supporting documents.
4. Support documents and reports.
5. Records of all communications between EPA personnel and persons
outside EPA pertaining to this supplemental proposal. (This does not
include any inter- 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 actions taken
by the Agency on dockets OPP-300368, OPP-300368A, OPP-300369, OPP-
300369A, OPP-300370, OPP-300370A, OPP-300371, and OPP-300371A (Ref.
16).

VIII. Regulatory Assessment Requirements

This action merely announces the availability of and requests
comments on additional data and/or information related to a proposed
rule that previously published in the Federal Register of November 23,
1994 (59 FR 60519). As such, the regulatory assessment requirements
imposed on rulemakings do not apply to this supplemental proposal.
Nevertheless, since there have been several revisions to the regulatory
assessment mandates that are imposed on rulemakings, the Agency
welcomes your comments on the following determinations.
Should the Agency finalize an exemption under FFDCA section 408,
and not impose any other requirements, such an action would not require
any special considerations under Executive Order 12898, entitled
Federal Actions to Address Environmental Justice in Minority
Populations and Low-Income Populations (59 FR 7629, February 16, 1994),
nor would it involve any technical standards that would require Agency
consideration of voluntary consensus standards pursuant to section
12(d) of the National Technology Transfer and Advancement Act of 1995
(NTTAA), Public Law 104-113, section 12(d) (15 U.S.C. 272 note).
Such an action would only directly affect growers, food processors,
food handlers and food retailers, not States. It would not impose any
enforceable duty or contain any unfunded mandate, and would not
otherwise significantly or uniquely affect small governments as
described under Title II of the Unfunded Mandates Reform Act of 1995
(UMRA) (Public Law 104-4). It would not require any prior consultation
as specified by Executive Order 13084, entitled Consultation and
Coordination with Indian Tribal Governments (63 FR 27655, May 19,
1998). Executive Order 13175, entitled Consultation and Coordination
with Indian Tribal Governments (65 FR 67249, November

[[Page 37869]]

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. EPA does
not expect its analysis to change, and will fully comply with the
requirements of Executive Order 13175 before promulgating any final
rules. For the same reasons, EPA does not expect these proposed actions
to have any substantial direct effect on States, on the relationship
between the national government and the States, or on the distribution
of power and responsibilities among the various levels of government,
as specified in Executive Order 13132, entitled Federalism (64 FR
43255, August 10, 1999). Such an action would not alter the
relationships or distribution of power and responsibilities established
by Congress in the preemption provisions of FFDCA section 408(n)(4).
Such an action would not require a regulatory flexibility analysis
under the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et seq.),
because an exemption from the requirement of a tolerance under FFDCA
section 408 would not adversely affect any small entities.
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.
For information about the applicability of the regulatory
assessment requirements to the previously published proposed rule,
please refer to the discussion in Unit XI. of that document (59 FR at
60533).

List of Subjects in 40 CFR Part 174

Environmental protection, Agricultural commodities, Pesticides and
pests, Plants.

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

[FR Doc. 01-17984 Filed 7-16-01; 11:42 am]
BILLING CODE 6560-50-S

Plant-Incorporated Protectants (Formerly Plant-Pesticides), Supplemental Proposal

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