[Federal Register Volume 66, Number 139 (Thursday, July 19, 2001)]
[Proposed Rules]
[Pages 37855-37869]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-17984]



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

[[Page 37855]]


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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:

 
------------------------------------------------------------------------
                                                        Examples of
           Categories               NAICS codes         potentially
                                                     affected entities
-----------------------------------------------------------------------
Pesticide manufacturers          32532              Establishments
                                                     primarily engaged
                                                     in the
                                                     formulation and
                                                     preparation of
                                                     agricultural and
                                                     household pest
                                                     control chemicals
------------------------------------------------------------------------
Seed companies                   111                Establishments
                                                     primarily engaged
                                                     in growing crops,
                                                     plants, vines, or
                                                     trees and their
                                                     seeds
------------------------------------------------------------------------
Colleges, universities, and      611310             Establishments of
 professional schools                                higher learning
                                                     which are engaged
                                                     in development
                                                     and marketing of
                                                     plant-
                                                     incorporated
                                                     protectants
------------------------------------------------------------------------
Establishments involved in       54171              Establishments
 research and development in                         primarily engaged
 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. http://www.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