[Federal Register Volume 66, Number 139 (Thursday, July 19, 2001)]
[Rules and Regulations]
[Pages 37830-37854]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-17983]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 174

[OPP-300368B; FRL-6057-6]
RIN 2070-AC02


Exemption From the Requirement of a Tolerance Under the Federal 
Food, Drug, and Cosmetic Act for Residues Derived Through Conventional 
Breeding From Sexually Compatible Plants of Plant-Incorporated 
Protectants (Formerly Plant-Pesticides)

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: The substances plants produce for protection against pests, 
and the genetic material necessary to produce these substances, are 
pesticides under the Federal Insecticide, Fungicide and Rodenticide Act 
(FIFRA), if humans intend to use these substances for ``preventing, 
destroying, repelling or mitigating any pest.'' These substances, 
produced and used in living plants, along with the genetic material 
necessary to produce them, are also ``pesticide chemical residues'' 
under the Federal Food, Drug, and Cosmetic Act (FFDCA). EPA calls these 
substances, along with the genetic material necessary to produce them, 
plant-incorporated protectants. In this final rule, EPA exempts from 
the FFDCA section 408 requirement of a tolerance, residues of the 
pesticidal substance portion and residues of any inert ingredient of 
any plant-incorporated protectant derived through conventional breeding 
from a plant sexually compatible with the recipient food plant. EPA has 
determined that there is a reasonable certainty that no harm will 
result from aggregate exposure to these residues.

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

ADDRESSES: Objections and hearing requests may be submitted by regular 
mail, electronically, or in person. Please follow the detailed 
instructions for each method as provided in Unit II. of the 
SUPPLEMENTARY INFORMATION.

FOR FURTHER INFORMATION CONTACT: By mail: Philip Hutton, Biopesticides 
and Pollution Prevention Division, Office of Pesticide Programs 
(7511C), Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington DC 20460; telephone number: (703)

[[Page 37831]]

308-8260; e-mail address: [email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Document Apply to Me?

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

 
------------------------------------------------------------------------
                                                         Examples of
           Categories                NAICS codes         potentially
                                                      affected entities
------------------------------------------------------------------------
Pesticide manufacturers          32532               Establishments
                                                      primarily engaged
                                                      in the formulation
                                                      and preparation of
                                                      agricultural and
                                                      household pest
                                                      control chemicals
------------------------------------------------------------------------
Seed companies                   111                 Establishments
                                                      primarily engaged
                                                      in growing crops,
                                                      plants, vines, or
                                                      trees and their
                                                      seeds
------------------------------------------------------------------------
Colleges, universities, and      611310              Establishments of
 professional schools                                 higher learning
                                                      which are engaged
                                                      in development and
                                                      marketing of plant-
                                                      incorporated
                                                      protectants
------------------------------------------------------------------------
Establishments involved in       54171               Establishments
 research and development in                          primarily engaged
 the life sciences                                    in conducting
                                                      research in the
                                                      physical,
                                                      engineering, or
                                                      life sciences,
                                                      such as
                                                      agriculture and
                                                      biotechnology
------------------------------------------------------------------------

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

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

    1. Electronically.You may obtain electronic copies of this 
document, and certain other related documents that might be available 
electronically, from the EPA Internet Home Page at http://www.epa.gov/. 
To access this document, on the Home Page select ``Laws and 
Regulations,'' ``Regulations and Proposed Rules,'' and then look up the 
entry for this document under the ``Federal Register--Environmental 
Documents.'' You can also go directly to theFederal Register listings 
at http://www.epa.gov/fedrgstr/. To access information about the EPA's 
program for biopesticides go directly to the Home Page for the Office 
of Pesticide Programs at http://www.epa.gov/pesticides/biopesticides.
    2. In person. The Agency has established an official record for 
this action under the docket control number OPP-300368B. The official 
record consists of the documents specifically referenced in this 
action, any public comments received during an applicable comment 
period, and other information related to this action, including any 
information claimed as Confidential Business Information (CBI). This 
official record includes the documents that are physically located in 
the docket, as well as the documents that are referenced in those 
documents. The public version of the official record, which includes 
printed, paper versions of any electronic comments submitted during an 
applicable comment period, is available for inspection in the Public 
Information and Record Integrity Branch (PIRIB), Rm. 119, Crystal Mall 
#2, 1921 Jefferson Davis Highway, Arlington, VA, from 8:30 a.m. to 4 
p.m., Monday through Friday, excluding legal holidays. The PIRIB 
telephone number is (703) 305-5805.

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

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

II. Objections and Hearing Requests

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

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

    You must file your objection or request a hearing on this 
regulation in accordance with the instructions provided in this unit 
and in 40 CFR part 178. To ensure proper receipt by EPA,

[[Page 37832]]

you must identify docket control number OPP-300368B in the subject line 
on the first page of your submission. All requests must be in writing, 
and must be mailed or delivered to the Hearing Clerk on or before 
September 17, 2001.
    1. Filing the request. Your objection must specify the specific 
provisions in the regulation that you object to, and the grounds for 
the objections (40 CFR 178.25). If a hearing is requested, the 
objections must include a statement of the factual issues(s) on which a 
hearing is requested, the requestor's contentions on such issues, and a 
summary of any evidence relied upon by the objector (40 CFR 178.27). 
Information submitted in connection with an objection or hearing 
request may be claimed confidential by marking any part or all of that 
information as CBI. Information so marked will not be disclosed except 
in accordance with procedures set forth in 40 CFR part 2. A copy of the 
information that does not contain CBI must be submitted for inclusion 
in the public record. Information not marked confidential will be 
included in the public version of the official record without prior 
notice.
    Mail your written request to: Office of the Hearing Clerk (1900), 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460. You may also deliver your request to the Office 
of the Hearing Clerk in Rm. C400, Waterside Mall, 401 M St., SW., 
Washington, DC 20460. The Office of the Hearing Clerk is open from 8 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
telephone number for the Office of the Hearing Clerk is (202) 260-4865.
    2. Tolerance fee payment. If you file an objection or request a 
hearing, you must also pay the fee prescribed by 40 CFR 180.33(i) or 
request a waiver of that fee pursuant to 40 CFR 180.33(m). You must 
mail the fee to: EPA Headquarters Accounting Operations Branch, Office 
of Pesticide Programs, P.O. Box 360277M, Pittsburgh, PA 15251. Please 
identify the fee submission by labeling it ``Tolerance Petition Fees.''
    EPA is authorized to waive any fee requirement ``when in the 
judgement of the Administrator such a waiver or refund is equitable and 
not contrary to the purpose of this subsection.'' For additional 
information regarding the waiver of these fees, you may contact James 
Tompkins by phone at (703) 305-5697, by e-mail at [email protected], 
or by mailing a request for information to Mr. Tompkins at Registration 
Division (7505C), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
    If you would like to request a waiver of the tolerance objection 
fees, you must mail your request for such a waiver to: James Hollins, 
Information Resources and Services Division (7502C), Office of 
Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania 
Ave., NW., Washington, DC 20460.
    3. Copies for the docket. In addition to filing an objection or 
hearing request with the Hearing Clerk as described in Unit II., you 
should also send a copy of your request to the PIRIB for its inclusion 
in the official record that is described in Unit I.B.2. Mail your 
copies, identified by docket control number OPP-300368B, to: Public 
Information and Records Integrity Branch, Information Resources and 
Services Division (7502C), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460. 
In person or by courier, bring a copy to the location of the PIRIB 
described in Unit I.B.2. You may also send an electronic copy of your 
request via e-mail to: [email protected]. Please use an ASCII file 
format and avoid the use of special characters and any form of 
encryption. Copies of electronic objections and hearing requests will 
also be accepted on disks in WordPerfect 6.1/8.0 file format or ASCII 
file format. Do not include any CBI in your electronic copy. You may 
also submit an electronic copy of your request at many Federal 
Depository Libraries.

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

    A request for a hearing will be granted if the Administrator 
determines that the material submitted shows the following: There is a 
genuine and substantial issue of fact; there is a reasonable 
possibility that available evidence identified by the requestor would, 
if established resolve one or more of such issues in favor of the 
requestor, taking into account uncontested claims or facts to the 
contrary; and resolution of the factual issues(s) in the manner sought 
by the requestor would be adequate to justify the action requested (40 
CFR 178.32).

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

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

[[Page 37833]]

result to infants and children from aggregate exposure to the pesticide 
chemical residue'' (21 U.S.C. 346a(b)(2)(C)(ii)(I)) and (c)(2)(B)). 
FFDCA section 408(b)(2)(D) specifies other general factors EPA must 
consider in establishing an exemption (21 U.S.C. 346a(b)(2)(D)). FFDCA 
section 408(c)(3) prohibits an exemption unless there is either a 
practical method for detecting and measuring levels of pesticide 
chemical residue in or on food or there is no need for such a method, 
requiring EPA to state the reason for this determination (21 U.S.C. 
346a(c)(3)).

IV. Context

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

    The substances plants produce for protection against pests are 
pesticides under the FIFRA definition of pesticide, if humans intend to 
use these substances for ``preventing, destroying, repelling or 
mitigating any pest.'' These substances, produced and used in living 
plants, along with the genetic material necessary to produce them, are 
designated ``plant-incorporated protectants'' by EPA.
    To understand the role this exemption plays in EPA's approach to 
plant-incorporated protectants, the following two considerations must 
be understood. First, what constitutes the residues of plant-
incorporated protectants derived through conventional breeding from 
plants sexually compatible with the recipient plant and why EPA is 
exempting them from the requirement of a tolerance. Second, how this 
exemption from the FFDCA requirement of a tolerance for residues of 
plant-incorporated protectants derived through conventional breeding 
from sexually compatible plants relates to the exemption from the FFDCA 
requirement of a tolerance published elsewhere in this issue of the 
Federal Register for residues of nucleic acids that are part of a 
plant-incorporated protectant.
    1. What constitutes the residues of plant-incorporated protectants 
derived through conventional breeding from sexually compatible plants 
and why is EPA exempting them? In developing its approach to plant-
incorporated protectants, EPA took into account the properties of 
pesticidal and other substances produced and used in plants. In 
particular, EPA recognized that plants have evolved, and thus naturally 
possess, various mechanisms to resist pests. The mechanisms of 
resistance can be varied, including, for example, structural 
characteristics of the plant, the production of general metabolites 
that have toxic properties, or the production of specific toxic 
substances in response to pest attack. In breeding plant varieties, 
humans have frequently intentionally used these mechanisms to create 
varieties with varying abilities to prevent, destroy, repel or mitigate 
pests. Based on human experience in breeding, growing, preparing, and 
consuming food from such plant varieties and the large and varied 
information developed through systematic scientific study available in 
the literature, EPA recognized that residues of many plant-incorporated 
protectants, in or on food or feed, would qualify for exemption from 
regulation under FFDCA section 408. (Hereafter, EPA will use the term 
``in food'' to represent the concept of ``in or on food or feed'' in 
this preamble).
    For EPA to exempt any residue of a pesticide, including any residue 
of a plant-incorporated protectant, EPA must find that there is a 
reasonable certainty that no harm will result from aggregate exposure 
to the residue, including all anticipated dietary exposures and all 
other exposures for which there is reliable information. EPA takes this 
action today with regard to residues of plant-incorporated protectants 
derived through conventional breeding from sexually compatible plants 
because it has determined that there is a reasonable certainty that no 
harm will result from aggregate exposure to the residues, including all 
anticipated dietary exposures and all other exposures for which there 
is reliable information.
    Under FFDCA section 408, the term residue is defined broadly to 
include residues of the active and inert ingredients of the pesticide 
itself and residues that are present in the food as a result of the 
metabolism or other degradation of the pesticide (21 U.S.C. 321(q)). 
For plant-incorporated protectants derived through conventional 
breeding from sexually compatible plants, EPA anticipates the residues 
will consist of the pesticidal substance and the genetic material 
necessary for production of the pesticidal substance, and any substance 
that might function as an inert ingredient as defined for plant-
incorporated protectants (e.g., any selectable marker), and the genetic 
material necessary for production of the inert ingredient.
    This action exempts from the requirement of a tolerance under FFDCA 
section 408, residues of the pesticidal substance portion of plant-
incorporated protectants derived through conventional breeding from 
plants sexually compatible with the recipient plant, and residues of 
any inert ingredient introduced through conventional breeding from 
plants sexually compatible with the recipient plant. For plant-
incorporated protectants, the recipient plant is the living plant that 
receives the genetic material necessary to produce the pesticidal 
substance and in which the plant-incorporated protectant is intended to 
be produced and used.
    2. How does this exemption relate to the exemption from the FFDCA 
requirement of a tolerance for residues of nucleic acids? This 
exemption can be paired with EPA's tolerance exemption for residues of 
nucleic acids that are part of a plant-incorporated protectant, 
published elsewhere in a companion document in this issue of the 
Federal Register. That exemption applies to residues of the genetic 
material portion of all plant-incorporated protectants, and, thus, also 
applies to residues of the genetic material necessary for the 
production of the pesticidal substance portion of plant-incorporated 
protectants derived through conventional breeding from sexually 
compatible plants, and the residues of the genetic material necessary 
for the production of any inert ingredient introduced through 
conventional breeding from plants sexually compatible with the 
recipient plant. Because of these actions, all residues of plant-
incorporated protectants derived through conventional breeding from 
sexually compatible plants are exempt from FFDCA section 408 
requirements.

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

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

[[Page 37834]]

    Residues of substances that are synthesized will not be covered by 
this exemption. Residues of such pesticides are subject to regulations 
found in 40 CFR parts 177 through 180 rather than 40 CFR part 174. An 
example of this type of pesticide is the herbicide, atrazine.

C. What Is the History of this Final Rule?

    This final rule is an additional step in fully implementing the 
``Coordinated Framework for Regulation of Biotechnology'' of the United 
States of America which was published in the Federal Register by the 
Office of Science and Technology Policy (OSTP) on June 26, 1986 (51 FR 
23302).
    EPA sponsored, or co-sponsored with other Federal agencies, three 
conferences dealing with plant related issues: On October 19-21, 1987, 
a meeting on``Genetically Engineered Plants: Regulatory 
Considerations'' at Cornell University, Ithaca, New York; on September 
8-9, 1988, a ``Transgenic Plant Conference'' in Annapolis, Maryland; on 
November 6-7, 1990, a conference on ``Pesticidal Transgenic Plants: 
Product Development, Risk Assessment, and Data Needs'' in Annapolis, 
Maryland. Information from these conferences has been incorporated as 
appropriate in development of this final rule.
    In developing its approach to plant-incorporated protectants, EPA 
requested the advice of two scientific advisory groups at three 
meetings. On December 18, 1992, pursuant to section 25 of FIFRA, a 
subpanel of the FIFRA Scientific Advisory Panel (SAP) was convened to 
review a draft policy on plant-pesticides (now called plant-
incorporated protectants) and to respond to a series of questions posed 
by the Agency, primarily on EPA's approach under FIFRA. On July 13, 
1993, EPA requested the advice of a subcommittee of the EPA 
Biotechnology Science Advisory Committee (BSAC) on a series of 
scientific questions dealing with EPA's approach to plant-pesticides 
under FFDCA. On January 21, 1994, a joint meeting of the subpanel of 
the SAP and the BSAC subcommittee was held and EPA asked advice on 
approaches to plant-pesticides under both FIFRA and FFDCA. Advice from 
these scientific advisory groups was considered in finalizing this 
rule.
    EPA published in the November 23, 1994, Federal Register a package 
of five separate documents (59 FR 60496, 60519, 60535, 60542, 60545) 
(FRL-4755-2, FRL-4755-3, FRL-4755-4, FRL-4755-5, FRL-4755-8) which 
described EPA's policy and proposals for plant-pesticides under FIFRA 
and FFDCA. Included in that package was a proposal to exempt from the 
FFDCA requirement of a tolerance, residues of the pesticidal substance 
portion of plant-pesticides derived from closely related plants.
    On July 22, 1996, EPA published a supplemental document in the 
Federal Register (61 FR 27891) (FRL-5387-4) on one aspect of its 
November 23, 1994, Federal Register documents; i.e., how the concept of 
inert ingredient related to plant-pesticides.
    In August of 1996, Congress enacted the FQPA which amended the 
FFDCA and FIFRA. On May 16, 1997, EPA published in the Federal Register 
a supplemental document (62 FR 27132) (FRL-5717-2) to provide the 
public with an opportunity to comment on EPA's analysis of how certain 
FQPA amendments to the FFDCA and FIFRA apply to the proposed tolerance 
exemption for pesticide chemical residues derived from closely related 
plants.
    On April 23, 1999, EPA published a supplemental document (64 FR 
19958) (FRL-6077-6) in the Federal Register soliciting comment on 
whether to change the name of this type of pesticide.
    The documents and the reports of the meetings described above are 
available in the record for the rulemaking for plant-incorporated 
protectants as described in Unit X.

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

    The development of this exemption consists of a proposed rule which 
appeared in the November 23, 1994, Federal Register (59 FR 60535), and 
two supplemental documents; one document that appeared on July 22, 
1996, in the Federal Register (61 FR 37891), and a second that appeared 
in the May 16, 1997, Federal Register (62 FR 27132).

A. November 23, 1994, Federal Register Proposed Rule

    In the 1994 Federal Register document (59 FR 60535, November 23, 
1994), EPA proposed to exempt residues of a category of plant-
pesticides it believed would qualify for an exemption. The proposed 
exemption was based upon the premise that new dietary exposures would 
not likely arise for these residues if the genetic material leading to 
the production of the pesticide chemical residues is derived from a 
plant that is closely related to the recipient plant; i.e., if the 
plant that is the donor of the genetic material is closely related to 
the plant receiving the genetic material.
    In the 1994 Federal Register document, EPA presented two options 
for describing a standard based on the relatedness of plants. Option 1, 
the Agency's preferred option proposed at 40 CFR 180.1137(a), used 
sexual compatibility as a measure of relatedness between plants. Under 
this option, residues of a pesticidal substance produced in a living 
plant as part of a plant-pesticide would be exempt from the requirement 
of a tolerance if 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 
plant and has never been derived from a source that is not sexually 
compatible with the recipient plant.
    Option 2 would utilize the rank of genus as the taxonomic standard 
for describing closely related plants, as well as sexual compatibility. 
This option would exempt residues of a pesticidal substance derived 
from a plant classified in the same genus as the recipient plant, as 
well as residues of a pesticidal substance derived from a plant 
sexually compatible with the recipient plant. Under both Options 1 and 
2, residues of the pesticidal substance derived from plants sexually 
compatible with the recipient plant would be exempt, even if the source 
and recipient plants are classified in different genera.
    EPA proposed that ``sexually compatible,'' when referring to 
plants, would mean ``capable of forming a viable zygote through the 
fusion of two gametes, including the use of bridging and/or wide 
crosses between plants.'' EPA proposed that ``bridging crosses between 
plants'' would mean the ``utilization of an intermediate plant in a 
cross between the intermediate plant and the 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 the first and third plant through the 
formation of an intermediate zygote.'' EPA proposed that ``wide crosses 
between plants'' would mean ``to facilitate the formation of viable 
zygotes through the use of surgical alteration of the plant pistil, bud 
pollination, mentor pollen, immunosuppression, in vitro fertilization, 
pre-pollination and post-pollination hormone treatments, manipulation 
of chromosome numbers, embryo culture, or ovary and ovule cultures or 
any other technique that the Administrator determines meets this 
definition.''

[[Page 37835]]

    Neither of the options was intended to exempt residues of a 
pesticidal substance that is significantly different functionally from 
the pesticidal substance as it occurs in the source plant.
    The Agency also requested comment on the utility of an exemption 
criterion based on the process (e.g., rDNA) used to introduce the 
plant-incorporated protectant into a plant (59 FR at 60514, 60540, 
60541). This approach was discussed by the SAP Subpanel and BSAC 
Subcommittee at the joint meeting of these scientific advisory groups 
held on January 21, 1994. In this approach, residues of plant-
incorporated protectants developed through techniques other than those 
of modern biotechnology would be exempted, e.g., residues of those 
plant-incorporated protectants developed through conventional plant 
breeding would be exempted. Residues of those plant-incorporated 
protectants that were not exempted could subsequently be considered for 
exemption on the basis of risk potential.
    The joint Subcommittee/Subpanel report justified such an approach 
on the following three considerations. First, the National Institutes 
of Health Guidelines for Research Involving Recombinant DNA Molecules 
established a precedent that has worked well. Second, although new 
techniques, such as rDNA are more precise than conventional plant 
breeding, it is possible to make with rDNA novel genetic modifications 
never before possible. The novel combinations possible with modern 
genetic techniques create uncertainties about how the gene will 
function and how its products may affect the plant's phenotype and its 
impact upon the environment and human health. Third, establishing rDNA 
methodologies as a criterion for oversight may give the public more 
confidence that risk potential is being evaluated. As a result, 
approved products may move to the marketplace more easily (Ref. 6).

B. What Issues Were Discussed in the Supplemental Documents?

    Subsequent to publication of the November 23, 1994 Federal Register 
document (59 FR 60535), EPA published two supplemental documents 
directly relevant to this exemption: one on July 22, 1996 (61 FR 
37891), and another on May 16, 1997 (62 FR 27132).
    1. July 22, 1996. The July 22, 1996, supplemental document (61 FR 
37891) discussed how the concept of inert ingredient related to plant-
pesticides.
    2. May 16, 1997. In August of 1996, the FFDCA and FIFRA were 
amended by the FQPA. On May 16, 1997, EPA published in the Federal 
Register, a supplemental document (62 FR 27132) to provide the public 
with an opportunity to comment on EPA's analysis of how certain FQPA 
amendments to the FFDCA and FIFRA affect this proposed exemption.
    EPA stated in the May 16, 1997, supplemental document its belief 
that most of the substantive factors the FFDCA now requires EPA to 
consider when evaluating pesticide residues were considered when the 
Agency proposed the exemption in 1994. EPA, thus, in the supplemental 
document, specifically sought comment only on its evaluation of the 
requirements imposed by FQPA that the Agency had not addressed in the 
proposed rule. EPA sought comment on the following five considerations. 
First, whether there are substances, outside of the food supply, 
sharing a common mechanism of toxicity with residues of pesticidal 
substances derived from sexually compatible plants. Commenters were 
asked to submit information on the cumulative effects of such 
substances and the pesticidal substances that were the subject of the 
proposed exemption (59 FR 60535). Second, whether there are substances, 
outside of the food supply, related via a common mechanism of toxicity 
to such residues to which humans might be exposed through non-
occupational routes of exposure. Commenters were asked to describe 
routes through which such exposure might occur, including exposure to 
major identifiable subgroups of human populations (e.g., infants and 
children). Commenters were requested, if such routes were identified, 
to provide information on the nature and levels of expected exposures. 
Comments were also sought on these two issues with regard to Option 2, 
the alternative option for describing closely related plants (described 
in Unit V.A.). Third, commenters who possess information on substances 
occurring in food from plants that may have estrogenic effects and may 
be used as plant-incorporated protectants were requested to send such 
information to EPA. Fourth, EPA described in greater detail the 
rationale supporting the statement made in the 1994 Federal Register 
document (59 FR at 60513) that ``plant-pesticides are likely to present 
a limited exposure of pesticidal substances to humans. In most cases, 
the predominant, if not the only, route of exposure will be dietary. 
Significant respiratory and dermal exposures will be unlikely.'' No 
comments were received on this statement during the first comment 
period for the proposed rule. The public was given the opportunity to 
comment on EPA's more detailed rationale supporting the statement. 
Fifth, EPA also described in greater detail how the rationale presented 
in the 1994 Federal Register document (59 FR at 60538) concerning the 
safety for human consumption of food from plants that meet the sexually 
compatible standard applies to infants and children. The public was 
given the opportunity to comment on the more detailed rationale 
specifically addressing infants and children as part of the larger 
human population.

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

    In this final rule, EPA exempts residues of the pesticidal 
substance and inert ingredient portion of plant-incorporated 
protectants derived through conventional breeding from plants sexually 
compatible with the recipient plant. The following language is added to 
40 CFR 174.479:

    Residues of a pesticidal substance that is part of a plant-
incorporated protectant 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 
from a plant that is sexually compatible with the recipient food 
plant.
    (b) The genetic material has never been derived from a source 
that is not sexually compatible with the recipient food plant.
    (c) The residues of the pesticidal substance are not present in 
food from the plant at levels that are injurious or deleterious to 
human health.

    Pertinent associated definitions in 40 CFR 174.3 are discussed in 
greater detail in a companion document published elsewhere in this 
issue of the Federal Register on FIFRA regulations for plant-
incorporated protectants.
    In this final rule, plant means an organism classified using the 5-
kingdom classification system of Whittaker (Ref. 1) in the kingdom, 
Plantae. Therefore, the term ``plant'' includes, but is not limited to, 
bryophytes such as mosses, pteridophytes such as ferns, gymnosperms 
such as conifers, and angiosperms such as most major crop plants.
    Also included in the regulatory text at Sec. 174.485, subpart X, is 
an exemption for residues of inert ingredients in plants derived 
through conventional breeding from sexually compatible plants.

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

    This exemption from the requirement of a tolerance is adopted with 
several

[[Page 37836]]

changes from the proposed rule published in 1994 (59 FR 60535, November 
23, 1994). EPA has changed the name of this type of pesticide from 
``plant-pesticide'' to ``plant-incorporated protectant'' as described 
in the companion document on FIFRA regulations for plant-incorporated 
protectants published elsewhere in this issue of the Federal Register. 
EPA exempts at this time only a subgroup of the category it proposed to 
exempt in 1994: Residues of pesticidal substances and inert ingredients 
derived through conventional breeding from plants sexually compatible 
with the recipient plant. In a companion document published elsewhere 
in this issue of the Federal Register, EPA solicits additional comment 
on alternative options for the plant-incorporated protectants derived 
through modern biotechnology, e.g., recombinant DNA techniques, from 
plants sexually compatible with the recipient plant.
    In response to concerns expressed in comments and to make EPA's 
approach more consistent with the policy of the Food and Drug 
Administration (FDA), EPA has added a condition to the exemption that 
addresses levels of substances that are injurious or deleterious to 
human health in food from plants in sexually compatible populations. A 
few other modifications have been made to the text of the exemptions, 
for purposes of clarification. A discussion of modifications to other 
relevant definitions, including an analysis of comments on those 
definitions, can be found in a companion document published elsewhere 
in this issue of the Federal Register on FIFRA regulations for plant-
incorporated protectants. Discussion of all modifications can be found 
in the documents summarizing public comments and EPA responses on 
issues associated with plant-incorporated protectants (Ref. 2) located 
in the record for this rule as described in Unit X.
    When EPA proposed the exemption in 1994 at 40 CFR 180.1137(a), it 
also stated its intention (59 FR at 60520) to establish a new 40 CFR 
part 174 specifically for plant-incorporated. This new 40 CFR part 174 
is being established in a companion document published elsewhere in 
this issue of the Federal Register. EPA adds this tolerance exemption 
to 40 CFR 174.479, subpart W, rather than adding it to 40 CFR part 180 
as proposed.

VIII. Discussion of Final Rule and Public Comments

    In this unit, EPA discusses the final rule and summarizes the 
comments it received on the November 23, 1994 proposed rule and the May 
16, 1997 supplemental document. EPA reviewed and considered all 
comments received on the proposed rule and supplemental document and 
prepared detailed responses to these comments. These responses can be 
found at appropriate points in this preamble and in the Agency's 
summary of public comments and EPA's response on issues associated with 
plant-incorporated protectants (Ref. 2).

A. From Whom Did EPA Receive Comments?

    In response to the package of documents published in the Federal 
Register in 1994, EPA received letters from industry, academia, 
professional and trade associations, government agencies, state 
regulatory authorities, public interest groups and private citizens. 
Some of the commenters sent separate letters for each of the five 
dockets associated with the 1994 Federal Register documents. Other 
commenters sent a single letter addressing all five dockets. EPA 
received comments on the July 22, 1996, supplemental document, and on 
the May 16, 1997, supplemental document, which provided the public an 
opportunity to comment on EPA's analysis of how certain amendments to 
the FFDCA and FIFRA by FQPA affected this proposed exemption. Copies of 
all comments received are available in the record for this rule as 
described in Unit X.

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

    On November 23, 1994 (59 FR 60535), EPA proposed to exempt from the 
FFDCA requirement of a tolerance, all residues of a category of plant-
incorporated protectants based on the premise that new dietary 
exposures would be unlikely if the genetic material leading to the 
production of the plant-incorporated protectant is derived from a plant 
closely related to the recipient plant. EPA offered two options for 
defining plant-incorporated protectants derived from plants closely 
related to the recipient plant. The options were somewhat different 
approaches to describing a high degree of relatedness between the 
genetic donor and the recipient plant. Neither of the options was based 
on the process by which a plant-incorporated protectant was introduced 
into the recipient plant. Option 1, based upon sexual compatibility, 
was EPA's preferred option (59 FR 60542). Option 2, used taxonomy 
(genus) in conjunction with sexual compatibility to define closely 
related plants. The Agency also requested comment on the utility of an 
exemption criterion based on the process (e.g., rDNA) used to introduce 
the plant-incorporated protectant into a plant (59 at FR 60514, 60540, 
60541).
    During the comment period for the 1994 proposed rule, EPA received 
19 comments addressing the options for describing pesticidal substances 
derived from closely related plants. Nine of these comments supported 
Option 1 and generally agreed that the sexual compatibility standard is 
reasonable and adequately addresses food safety issues. Three comments 
favored Option 2, with one of these comments arguing that species 
belonging to the same genus are closely related and thus have a high 
degree of biochemical similarity even though they may not be sexually 
compatible. The commenter also cited the history of safe use of foods 
from plant varieties developed through plant breeding. EPA also 
received comments expressing serious reservations about using, for this 
exemption, a taxonomic standard for describing closely related plants 
(i.e., Option 2), because taxonomic categories, and the relationship of 
a given plant species to a given taxon, may be transient since 
taxonomic categories may change as information accrues. Others 
expressed concern that dietary risk may be presented by such a 
standard.
    EPA received 37 comments on the use of the process by which the 
genetic material is introduced into the plant as an exemption 
criterion. Twenty of these comments supported an approach based on 
process, i.e., that those plant-incorporated protectants introduced by 
rDNA would be regulated. The arguments advanced by these commenters can 
be represented by the comment that:

    Genetic engineering (particularly recombinant DNA [rDNA] 
methodologies), represents a fundamental technical advance over 
traditional plant breeding in the ability to manipulate plants 
genetically. Genes which code for production of plant-pesticides can 
be readily turned `on' or `off' to dramatically increase the 
existing levels of plant-pesticides within plants, turning plants 
into pesticide factories and delivery systems. . . . given the fact 
that rDNA technologies represent such a fundamental technical 
advance over plant breeding, and given that plant-pesticides are by 
their very nature toxic substances, all plant-pesticides produced 
via rDNA methodologies should undergo some form of review under both 
FIFRA and FFDCA . . . (Ref. 3).

    Several letters described quantitative changes in the levels of 
plant-incorporated protectants as specific

[[Page 37837]]

instances in which the commenter believed risk would be better 
addressed by an approach based on process. One of these commenters did 
not agree with EPA's analysis that levels of the plant-incorporated 
protectants (and thus of their residues) are likely to fall, in the 
vast majority of cases, within ranges currently found in safely 
consumed food from plants. Another of these commenters urged EPA to 
modify the proposed exemption so that the Agency would be notified if 
levels of pesticidal substances are ``deliberately increased through 
the introduction or modification of promoters or other noncoding 
regulatory sequences or there is reason to believe that levels of a 
plant-pesticide in food or feed derived from a particular crop will be 
increased by an order of magnitude or more'' (Ref. 3).
    In response to the May 16, 1997, supplemental document, EPA 
received six comments. Five comments supported exemption of residues of 
plant-incorporated protectants derived from sexually compatible plants, 
with four comments addressing specific questions posed by EPA. One 
commenter, however, opposed any exemption that did not take into 
account quantitative changes in the levels of these residues, stating 
that ``current knowledge is certainly inadequate to sanction greatly 
increased levels of these substances'' in food (Ref. 4).
    Some comments urging regulation based on whether rDNA had been used 
to introduced the plant-incorporated protectant, supported exempting 
conventional breeding. One commenter, for example, stated ``that a long 
record of experience with the products of natural evolution and 
traditional breeding shows that they typically do not present new 
dietary exposures and should be exempt from tolerance requirements'' 
(Ref. 5).
    Based on the advice of the BSAC and SAP at the joint meeting held 
January 21, 1994, and the comments received in response to the November 
23, 1994 Federal Register document, EPA has determined that it is 
appropriate at this time to exempt from the FFDCA tolerance requirement 
those residues of the pesticidal substance portion of plant-
incorporated protectants, as well as any inert ingredients derived 
through conventional breeding from plants sexually compatible with the 
recipient plant. In a companion document published elsewhere in this 
issue of the Federal Register, EPA solicits public comment on 
alternative options for the category of residues of pesticidal 
substances derived through the techniques of modern biotechnology, 
e.g., recombinant DNA, from plants sexually compatible with the 
recipient plant. The Agency is considering these options in response to 
public comment on its earlier proposals. One of these options would 
establish notification procedures, and as the public has not had an 
opportunity to comment on either the procedures themselves, or the 
criteria on which EPA would base its regulatory decisions, the Agency 
believes it would be appropriate to seek additional public comment 
prior to adopting a particular option. In addition, as these 
alternatives would distinguish between categories of residues of plant-
incorporated protectants based solely on the processes by which they 
are derived, the public will also have an opportunity to present 
comments on whether this is an appropriate distinction for regulatory 
purposes.

C. What is the Language of the Exemption?

    In this final rule, EPA is, at 40 CFR 174.479, exempting only a 
subgroup of the category of residues it proposed to exempt in 1994, 
pesticide chemical residues derived through conventional breeding from 
plants sexually compatible with the recipient plant. EPA discusses the 
language of the exemption as it applies to this subcategory.
    1. Why is sexual compatibility an appropriate standard? EPA 
believes that sexual compatibility is an appropriate standard because 
sexually compatible plants share a common pool of genetic material, 
even though there may be some variability among plants in sexually 
compatible populations. Sexual compatibility, the ability to produce 
viable offspring, is only possible in nature for plants that possess 
many traits in common. Traits, and the genetic material encoding them, 
can be passed through sexually compatible plant populations by 
hybridization, and the mixing of genetic material that occurs through 
this process of mating tends to a situation where the members of 
sexually compatible population have similar traits and similar genetic 
material. This is particularly true with crop plants where generations 
of selection and breeding have tended to increase the homogeneity of 
traits used to produce agriculturally important cultivars. Sexual 
compatibility thus presents a natural grouping of plants which can be 
readily described and used as a regulatory standard, and about which a 
large amount of information exists in the scientific literature. This 
information can be used in assessing risk.
    Using sexual compatibility as a standard affords a clear 
delineation of whether the residues of a plant-incorporated protectant 
meet the conditions of the exemption. In most cases, whether two plants 
are sexually compatible is known; thus, testing to determine whether 
the plants are sexually compatible is not likely to be necessary. If, 
in rare cases, it is not known whether two plants are sexually 
compatible, the means of determining sexual compatibility is 
straightforward and simple. Sexual compatibility is empirically 
demonstrable. EPA believes that the criterion of sexual compatibility 
provides a high level of regulatory clarity and the greatest ease of 
implementation, while at the same time presenting the lowest 
probability of novel dietary exposure. This standard allows the public, 
industry, and EPA to easily and readily identify those plant-
incorporated protectants that meet the criterion of being derived from 
plants closely related to the recipient plant.
    i. Why is sexual compatibility limited to conventional breeding? As 
explained in a companion document published elsewhere in this issue of 
the Federal Register, EPA is soliciting additional comment on the 
various options it is considering in response to the significant 
comments it has received raising issues specific to plant-incorporated 
protectants derived through genetic engineering. Because none of the 
comments raised significant issues relative to pesticide chemical 
residues of plant-incorporated protectants derived through conventional 
breeding, the Agency is finalizing its proposals with respect to 
residues of this subgroup of products. In a final rule under FIFRA 
described elsewhere in a companion document in this issue of the 
Federal Register, EPA includes in the definition of sexually compatible 
at 40 CFR 174.3 the clause ``through conventional breeding.'' EPA also 
provides a definition of conventional breeding that equates it to the 
creation of progeny through either: The union of gametes, i.e., 
syngamy, brought together through processes such as pollination, 
including bridging crosses between plants and wide crosses; or 
vegetative reproduction. Conventional breeding does not include use of 
any of the following technologies: Recombinant DNA; other techniques 
wherein the genetic material is extracted from an organism and 
introduced into the genome of the recipient plant through, for example, 
micro-injection, macro-injection, micro-encapsulation; or cell fusion. 
EPA believes that this

[[Page 37838]]

definition addresses the recommendation of the SAP/BSAC that ``the 
Agency define methodologies in a way that clearly delineates to the 
scientific community and the public what is and is not included in the 
regulatory scope'' (Ref. 6).
    In the 1994 proposed rule (59 FR at 60538) and in the 1997 
supplemental document (62 FR at 27135), EPA states that its proposed 
rule is based on ``experience with the exposure of human populations to 
crops developed through the breeding process, i.e., crops developed 
through 50 to 100 years of scientific breeding among sexually 
compatible plant populations using Mendelian genetics.'' In its 1994 
proposed rule, EPA calls this type of breeding, ``traditional 
breeding'' (see e.g., 59 FR 60519). When the Agency determined that it 
would exempt a subgroup of residues of the sexually compatible 
grouping, while allowing additional comment on how the Agency should 
treat the residues of those plant-incorporated protectants introduced 
into the plant through the techniques of modern biotechnology, EPA 
chose to describe the exempt group of residues in the most 
straightforward manner, as those derived through breeding in sexually 
compatible populations. Recognizing that many consider the modern 
techniques of biotechnology as simply an extension of breeding 
techniques, EPA determined that an adjective was needed to modify the 
word ``breeding'' to adequately describe the exempt group. Although the 
Agency used the word ``traditional'' in its 1994 proposed rule, EPA 
chose the word ``conventional'' to describe this type of breeding in 
this rule because the SAP/BSAC in the report of their January 21, 1994 
joint meeting used the adjective ``conventional'' in its advice to EPA 
(Ref. 6), and the word ``conventional'' might more readily connote 
techniques such as wide crosses.
    ii. Why is conventional breeding described by processes such as 
pollination and vegetative reproduction? One comment received on the 
1994 proposed rule suggested that there is ambiguity in the proposed 
regulatory language at 40 CFR 174.5(a) in the November 23, 1994, 
Federal Register document (59 FR 60535). The commenter indicated the 
perceived ambiguity could lead to questions about whether plant-
incorporated protectants that are ``native'' to a food crop would meet 
the criteria of exemption.
    Because of the use of the word ``food'' in the comment, it was not 
clear whether the comment is directed toward EPA's proposed exemption 
under FIFRA or that under the FFDCA for residues of plant-incorporated 
protectants derived from plants sexually compatible with the recipient 
plant. EPA assumes this comment is directed at both exemptions, and 
that the commenter's suggestion is that EPA ensure that the regulatory 
language exempts from the FFDCA tolerance requirements, residues of 
those plant-incorporated protectants that normally occur in a plant 
(i.e., are ``native'' to the plant) and will be used in that plant. For 
example, if corn normally produced a plant-incorporated protectant, the 
regulatory text should be clear that the residues of the plant-
incorporated protectant would be exempt when produced and used in corn. 
EPA believes inclusion of the word ``pollination'' as an example of a 
process leading to syngamy in the definition of conventional breeding 
addresses this concern. EPA believes the word ``pollination'' is 
appropriate because pollination is the process through which 
traditional breeding occurs (see e.g., 59 FR 60537) (Ref. 7). Inclusion 
of the word ``pollination'' in the definition emphasizes that plant-
incorporated protectants that occur naturally in a plant growing from a 
viable zygote that arises by the mating in conventional breeding of one 
corn variety with another, or the mating of a corn plant with a corn 
plant of the same variety, are exempt.
    EPA recognizes that this same concern also applies to plant-
incorporated protectants in plants that are propagated vegetatively. 
EPA believes inclusion of the phrase ``vegetative reproduction'' in the 
definition of conventional breeding addresses this concern. The 
language of the exemption for pesticide chemical residues derived 
through conventional breeding from sexually compatible plants 
specifically exempts residues in plants reproduced vegetatively. For 
example, residues of a plant-incorporated protectant in a plant 
propagated only vegetatively, (e.g., bananas), are exempt. Also exempt 
are residues of a plant-incorporated protectant in a plant propagated 
primarily vegetatively (e.g., potatoes), as long as, under conditions 
of reproduction through hybridization, the plant donating the genetic 
material is sexually compatible with the recipient plant as defined in 
at 40 CFR 174.3, and the other conditions described at 40 CFR 174.479 
are met. Inclusion of this term in the definition of conventional 
breeding reflects EPA's statement in the 1994 proposed rule (59 FR 
60524) on the status of crop plant varieties propagated vegetatively.
    iii. Will wide and bridging crosses be part of the definition of 
conventional breeding? In the final rule under FIFRA described 
elsewhere in a companion document in this issue of the Federal 
Register, EPA defines ``conventional breeding'' to include wide and 
bridging crosses. These definitions are also important to this FFDCA 
tolerance exemption, and thus, EPA discusses them in this preamble.
    In the final rule, wide crosses include use of surgical alteration 
of the plant pistil, bud pollination, mentor pollen, 
immunosuppressants, in vitro fertilization, pre-pollination and post-
pollination hormone treatments, manipulation of chromosome numbers, 
embryo culture or ovary and ovule cultures. Generations of artificial 
hybridizations through these techniques have taken place in the well-
established practices of plant breeding (Ref. 8). Wide crosses, have 
been in the past and are currently, commonly used to expand the plant 
gene pool for varietal improvement, and a history of safe use has been 
associated with plant varieties developed through the use of wide cross 
techniques (Ref. 8). A fairly high degree of relatedness between the 
parental plants is indicated when a wide cross produces a viable 
zygote. This high degree of relatedness indicates a low probability of 
new exposures. Agricultural plants safely consumed as food have been 
developed in the past 100 years utilizing wide crosses in the breeding 
process.
    The definition of ``bridging crosses between plants'' is intended 
to convey the concept that an intermediate plants could be used in a 
cross to move traits from a source plant into a desired recipient 
plant. The intermediate plant can form viable zygotes with both the 
source and recipient plants, whereas the source and recipient plant 
cannot form viable zygotes. The intermediate plant serves as a bridge 
for gene flow between the two incompatible plants. The result of the 
bridging cross is the mixing of genetic material of the first and third 
plant through the formation of an intermediate zygote. No comments were 
received on the proposed definition of bridging crosses between plants, 
also part of the definition of conventional breeding for sexually 
compatible. EPA is adopting this definition as proposed.
    iv. Will cell or protoplast fusion be part of the definition of 
wide crosses? EPA received one comment suggesting that protoplast 
fusion should be included in the definition of wide crosses between 
plants. That request was made in the context of the proposal to exempt 
plant-incorporated protectants derived from plants sexually

[[Page 37839]]

compatible with the recipient plant from FIFRA requirements, but as the 
definition of wide crosses is also relevant for this FFDCA exemption, 
EPA will discuss that comment in this preamble.
    In the technique of protoplast fusion, protoplasts are made in the 
laboratory through the removal of the cell walls of somatic cells. A 
somatic cell is a type of cell that forms plant vegetative tissues and 
organs and is distinguished from a germ cell which undergoes meiosis to 
produce reproductive tissues (e.g., pollen and egg cells). In the 
technique of protoplast fusion, protoplast are made from the somatic 
tissues of two different plants. The membranes of the different 
protoplasts are then fused together mechanically through processes such 
as treatment with polyethylene glycol, producing a hybrid somatic cell 
with a genetic make-up resulting from the combination and sorting of 
the two plant genomes. The somatic hybrid cell is then grown on 
specialized media into a mature plant.
    In support of the request, the commenter argued that the 
hybridization of somatic cells (i.e., protoplast fusion) has a history 
of use to artificially induce sexual compatibility. The commenter 
argued that movement of genetic material by this means has historically 
been considered safe.
    EPA did not, in its 1994 proposed rule include protoplast fusion in 
the definition of wide crosses between plants, nor did it perform an 
analysis of the potential for new dietary exposures when protoplast 
fusion is used to perform wide crosses between plants. The commenter 
did not provide such information in response to the 1994 proposed rule 
nor the 1997 supplemental document. EPA does not believe information 
currently in the record supports inclusion of protoplast fusion in the 
definition of wide crosses. Therefore, EPA does not include protoplast 
fusion in the definition of wide crosses and specifically excludes cell 
fusion from the definition of conventional breeding. However, EPA 
requests comment on whether protoplast fusion should be included in the 
definition of wide crosses in a supplemental document published 
elsewhere in this issue of the Federal Register. EPA would welcome 
submission of information on protoplast fusion. If the Agency obtains 
sufficient information demonstrating a low probability of risk, EPA may 
initiate notice-and-comment rulemaking under FIFRA section 25(b) and 
FFDCA section 408 to include protoplast fusion in the definition of 
wide crosses between plants.
    v. ``Recombinant DNA'' and genetic material ``extracted from an 
organism and introduced into the genome of the recipient plant.'' As 
explained previously, EPA restricted this exemption to conventionally 
bred plant-incorporated protectants while the Agency solicits 
additional comment on the alternatives it is considering in response to 
the comments received on the 1994 proposal. Thus, in order to fully 
describe which plant-incorporated protectants are exempt under this 
exemption, EPA includes limiting phrases. EPA in the 1994 Federal 
Register document (59 FR 60541, November 23, 1994) discussion of the 
advice of the joint SAP/BSAC at the January 21, 1994 meeting on the use 
of a process-based criterion to define a category of plant-incorporated 
protectants that would be subject to review, stated that the Agency 
would define such a process-based criterion in the following way: ``The 
genetic material that encodes for the pesticidal substance or leads to 
the production of the pesticidal substance is extracted from an 
organism and introduced into the genome of the recipient plant or is 
synthesized in vitro and introduced into the genome of the recipient 
plant.'' EPA in this action uses the language it put forth in the 1994 
Federal Register to fashion two of the exclusions from the conventional 
breeding definition at 40 CFR 174.3. One exclusion is for techniques 
involving the direct introduction into an organism of genetic material 
extracted from the source and introduced into a recipient plant. 
Processes such as micro-injection, macro-injection and micro-
encapsulation would be excluded from the conventional breeding 
definition because they are used to introduce such extracted genetic 
material into the recipient plant. These processes have been included 
in the definition as examples to assist in understanding the concept.
    The second exclusion from the conventional breeding definition uses 
the term ``recombinant DNA'' to represent the concept of ``extracted 
from an organism. . ., synthesized in vitro and introduced into the 
genome of the recipient plant.'' To provide greater technical accuracy, 
EPA provides a definition at 40 CFR 174.3 for recombinant DNA as 
follows: ``Recombinant DNA means the genetic material has been 
manipulated in vitro through the use of restriction endonucleases and/
or other enzymes that aid in modifying genetic material, and 
subsequently introduced into the genome of the plant.''
    2. Why is the concept of ``functionally modified from the source'' 
important and how does the definition of conventional breeding address 
it? In the November 23, 1994 Federal Register document (59 FR at 
60539), EPA explained that in proposing the exemptions the Agency did 
not intend to exempt residues of a pesticidal substance that is 
significantly different functionally, from the pesticidal substance as 
it occurs in the source plant. EPA believed this limitation is 
appropriate because rearrangements or modifications of the genetic 
sequence encoding a pesticidal substance made through the use of 
techniques such as rDNA could, for example, result in a plant-
incorporated protectant, and/or residues of such 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. 8 and 9). 
Residues of such a significantly modified pesticidal substance would 
not necessarily present risks similar to the substance prior to 
modification, nor would the base of experience on which EPA relies for 
support of the exemption necessarily be relevant. If the genetic 
material encoding the pesticidal 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 there is a reasonable certainty that no harm will 
result from aggregate exposure to the residues of the plant-
incorporated protectant, would not apply.
    In this final rule, this concern is addressed by the limitation 
placed on the definition of sexually compatible. Under this definition, 
residues of pesticidal substances from sexually compatible plants are 
only exempt if the genetic material is introduced into the plant 
through conventional breeding as defined at 40 CFR 174.3. The types of 
changes discussed above (Refs. 8 and 9) that can be made through modern 
molecular techniques, are very unlikely to be made through conventional 
breeding as defined at Sec. 174.3, and residues of plant-incorporated 
protectants modified through modern molecular techniques are not 
eligible for today's exemption.
    3. Why is the phrase ``never derived from source not sexually 
compatible with recipient plant'' important? EPA discussed the 
relevance of this phrase to the proposed exemption in the November 23, 
1994 Federal Register

[[Page 37840]]

document (59 FR 60539). The phrase, ``has never been derived from a 
source that is not sexually compatible with the recipient plant,'' was 
included in the proposed regulatory text to clearly indicate that 
pesticide chemical residues of a plant-incorporated protectant would 
not qualify for the exemption if the genetic material is introduced 
into a recipient plant from a sexually incompatible source and then 
subsequently introduced from this recipient plant into other plants 
sexually compatible with the recipient plant. For example, the 
exemption does not extend to a situation where the genetic material 
encoding the Bacillus thuringiensis delta endotoxin is introduced into 
wheat, and the endotoxin-producing wheat is subsequently hybridized 
with rye using wide cross techniques to produce triticale. The residues 
of the endotoxin produced in the triticale would not be eligible for 
the exemption because the genetic material encoding the endotoxin 
originated from a bacterium, a source that is not sexually compatible 
with the original recipient plant (wheat in this example).
    One commenter suggested that the Agency delete this phrase from the 
regulatory text and instead include a period of time after which a 
plant-incorporated protectant would be treated as part of a plant's 
``accessible'' gene pool. EPA disagrees and will continue to include 
this language in the final rule at 40 CFR 174.479. Further, EPA 
disagrees with the commenter's suggestion that a gene, derived from a 
phylogenetically distant source and successfully used in a crop, be 
treated after a period of time as though it had become part of the 
crop's gene pool (i.e., equivalent to a gene that had evolved in a 
sexually compatible population of plants). The commenter does not 
suggest what an appropriate period of time would be nor how this would 
correlate with the potential for dietary exposures. Without additional 
information, EPA cannot find that there is a ``reasonable certainty 
that no harm will result from aggregate exposure to the pesticide 
chemical residue'' as required by FFDCA section 408(c).
    4. Why is EPA placing a condition on the exemption limiting the 
levels of pesticidal substances? To address concerns raised in comment 
on its original proposal concerning the possibility that certain 
substances normally present in plants in sexually compatible 
populations may in rare circumstances be present in food at levels that 
are hazardous, EPA is limiting this exemption by requiring that the 
residues of the pesticidal substance not be present in food from the 
plant at levels that are injurious or deleterious to human health. EPA 
is including at 40 CFR 174.479, the following condition to the language 
of the exemption: ``(c) The residues of the pesticidal substance are 
not present in food from the plant at levels that are injurious or 
deleterious to human health.''
    If the residues of the plant-incorporated protectant do not meet 
this criterion, they are not exempt from the requirement of a 
tolerance, nor would a tolerance have been established for them. A food 
containing residues of a pesticide may not be moved in interstate 
commerce without either an appropriate tolerance or an exemption from 
the requirement of a tolerance. Should such an occurrence be 
identified, the condition will allow expeditious removal of the 
offending food from the market. EPA does not believe that such an 
occurrence will result a priori in a reevaluation of the categorical 
exemption for pesticidal substances derived through conventional 
breeding from sexually compatible plants under FFDCA section 408 
because any problem will likely be associated with a single variety.
    Producers who wish to increase the levels of pesticidal substances 
in plants in sexually compatible populations beyond the ranges of 
levels generally seen in plant varieties currently on the market and 
known to produce food safe for consumption are strongly encouraged to 
consult with EPA to determine whether their plant-incorporated 
protectant is eligible for the exemption from the requirement of a 
tolerance, or whether a tolerance, and therefore, a registration is 
necessary. Based on the record compiled for this rulemaking on the 
historical safety of food from plants in sexually compatible 
populations, as described in Unit IX.A. and Unit IX.B.1., EPA believes 
that such a circumstance, will be extremely unlikely for residues 
derived through conventional breeding from plants sexually compatible 
with the recipient plant.
    This condition makes EPA's approach to plant-incorporated 
protectants more consistent with FDA's regulatory approach, and allows 
the agencies to act more expeditiously in the rare circumstance that a 
risk associated with higher levels of substances normally part of a 
plant in a sexually compatible population is identified in food.
    This condition, in conjunction with the reporting requirement at 40 
CFR 174.71, is conceptually similar to the suggestion of one commenter 
that the Agency be notified if levels of pesticidal substances are 
significantly increased. EPA disagrees, however, with the commenter's 
suggestion that notification be required only when levels of pesticidal 
substances are increased by 10 fold. There is natural variability in 
levels of expression in a plant of any substance, including plant-
incorporated protectants, influenced by factors such as genetic 
composition, soil composition, climate and weather. Humans are 
currently being exposed to variation in the food they consume. The 
commenter did not provide information to support the suggestion that a 
10-fold increase would represent an unacceptable risk, and broad 
adoption of such a standard would be arbitrary. The variations normally 
seen in food from plants, such as the 20-fold variation for ascorbic 
acid in muskmelon depending on variety planted, and the variation in 
the levels of carotene in carrots which can range from none detectable 
to 370 mg/100 g tissue depending on the variety (Ref. 8), are greater 
than the 10-fold increase suggested by comment. Other examples can be 
offered where the variation falls within a more narrow range, for 
example, one researcher (Ref. 8) reported that depending on maturity of 
the fruit, the level of ascorbic acid in tomato can range from 2.7 mg/
100 g tissue to 7.6 mg/100 g tissue, a 2.8-fold variation. The 
conditions on the exemption at Sec. 174.479 and reporting requirement 
at Sec. 174.71, on the other hand, have no numerical standards. 
Nevertheless, the Agency believes that the adverse effects reporting 
requirement will allow the Agency to monitor for any rare instances in 
which significant increases in levels of plant-incorporated protectants 
might present a hazard, and that the condition at Sec. 174.479 will 
allow EPA and FDA to act expeditiously. (The adverse effects reporting 
requirement is described in a companion document published elsewhere in 
this issue of the Federal Register on FIFRA regulations for plant-
incorporated protectants).
    The historical safety of the food supply as described by the record 
EPA has compiled for this exemption, the reporting requirement imposed 
as a condition of the FIFRA exemption, taken in conjunction with the 
strong likelihood that manufacturers and companies will choose to 
consult with EPA rather risk seizure of their food by FDA, cause EPA to 
believe that the condition placed on the exemption sufficiently address 
the commenters' concerns.
    5. Why does 40 CFR 174.479 include language limiting the recipient 
to food plants? In the preamble to the 1994

[[Page 37841]]

proposed rule (see e.g., 59 FR 60537), EPA discussed the premise for 
this exemption; that ``new dietary exposures would not likely arise for 
plant-pesticides produced in recipient food plants if the genetic 
material leading to the production of the pesticidal substance is 
derived from closely related plants.'' In addition, the BSAC in its 
report on the July 13, 1993 meeting (Ref. 10) emphasized to the Agency 
that the focus of an exemption should be on plant-incorporated 
protectants in food plants. They suggested that ``plant-pesticides in 
plants commonly consumed by humans as food be exempt as long as the 
plant's genetic material is derived from related plants within the same 
family that have contributed traits to the food plant through the 
mechanism of sexual recombination (including wide crosses and embryo 
rescue)'' (59 FR 60540). In this final rule, EPA has revised 
Sec. 174.479 to clearly state that the recipient plant must be a food 
plant by including the phrase ``recipient food plant'' in the 
regulatory text at Sec. 174.479(a) and (b). In the final rule, EPA has 
revised the definition of ``food plant'' proposed in the 1994 proposed 
rule at 40 CFR 180.1137 (59 FR at 60542) to read: ``Food plant means a 
plant which, either in part or in toto, is used as food''. EPA includes 
this definition at 40 CFR 174.3. EPA also includes at Sec. 174.3 the 
definition of food found in the FFDCA. Thus, for these regulations for 
plant-incorporated protectants: Food includes articles used for food or 
drink by humans or other animals.
    6. What is the status of substances within sexually compatible 
plant populations that might be used as inert ingredients? In a 
companion document published elsewhere in this issue of the Federal 
Register, EPA describes its consideration of inert ingredients in light 
of existing regulations and comments received in response to both the 
November 23, 1994 Federal Register document (59 FR 60534) and a 1996 
supplemental document (61 FR 37891) discussing the Agency's treatment 
of selectable markers as inert ingredients for plant-incorporated 
protectants. In the companion document published elsewhere in this 
Federal Register on FIFRA regulations, EPA describes its determination 
that it will apply the concept of inert ingredients to plant-
incorporated protectants consistent with the 1994 proposal.
    The preamble discussion in the 1994 Federal Register document (59 
FR at 60523) of the rationale supporting the proposal to exempt plant-
incorporated protectants derived from sexually compatible plants 
extends to any substance that is derived from plants sexually 
compatible with the recipient plant, including substances such as a 
selectable marker, used to confirm or ensure the presence of the active 
ingredient. EPA's analysis in Unit IX., applies equally to all the 
substances that normally are found in a population of sexually 
compatible plants, including inert ingredients as long as these are 
derived through conventional breeding from plants sexually compatible 
with the recipient plant, and have never been derived from a source 
that is not sexually compatible with the recipient plant. An example of 
such an inert ingredient in sexually compatible populations could be 
tightly linked traits, such as unusual leaf pigmentation always found 
with a pest resistance trait.
    EPA includes these residues at 40 CFR part 174, subpart X, to 
ensure that readers understand that any trait used as a selectable 
marker, and the genetic material necessary to produce it, that occurs 
normally in a plant sexually compatible with the recipient plant or is 
introduced through conventional breeding, is exempt from the FFDCA 
section 408 requirement of a tolerance, as well as FIFRA requirements 
on inert ingredients when used with a plant-incorporated protectant 
derived through conventional breeding from a plant sexually compatible 
with the recipient plant. EPA believes this interpretation is a logical 
implication of the preamble discussion in the 1994 proposed rule (59 FR 
at 60538).
    Because the Agency recognizes that a substance described in Unit 
IX.B.2. (i.e., a toxicant) could theoretically be used as an inert 
ingredient, EPA places the same limiting condition on residues of the 
inert ingredient in food as is placed on residues of the pesticidal 
substance portion of the active ingredient; i.e., the residues of the 
inert ingredient do not qualify for the exemption if they are present 
in food from the plant at levels that are injurious or deleterious to 
human health.
    Discussion supporting this exemption can also be found in a 
companion document published elsewhere in this issue of the Federal 
Register on FIFRA regulations for plant-incorporated protectants. 
Regulatory text has been established at 40 CFR 174.485, subpart X, 
which is entitled ``Inert ingredients from sexually compatible 
plant,''in a companion document on FIFRA regulations for plant-
incorporated protectants published elsewhere in this issue of the 
Federal Register.

D. What Were the Other Potential Approaches to the Scope of Exemption?

    In the November 23, 1994 Federal Register document (59 FR 60537), 
EPA discussed the merits of an approach using taxonomy, along with 
sexual compatibility (Option 2), as a standard for describing closely 
related plants, and received comment on use of such a criterion. EPA 
also received a comment, made in the context of the FIFRA regulations, 
suggesting that the criterion of sequence homology be used to limit the 
concept of sexual compatibility. In light of the relevance of this 
comment to this FFDCA exemption, EPA discusses this suggestion, as well 
as the comments on taxonomy, here. EPA also discusses a comment 
suggesting that EPA consider extending the exemption, on a case-by-case 
basis, to residues of plant-incorporated protectants derived from 
plants unrelated to the recipient plant, and a suggestion that 
exemptions should be based on a documented history of safe use.
    1. Taxonomy. Two commenters expressed reservation about using a 
taxonomic standard for describing closely related plants. They pointed 
out that taxonomic categories, and the relationship of a given plant 
species to a given taxon, may be transient since taxonomic 
classification may change as information accrues. EPA agrees. In the 
1994 Federal Register document, EPA noted (59 FR at 60524) that a 
taxonomy- based standard (e.g., Option 2) may be artificial: 
classification of plants in different taxonomic genera is not fixed and 
could change over time and between scientific authorities. Taxonomy 
reflects current observations about phenotypic, and to some extent, 
genotypic, differences between organisms. Currently, some plant genera 
are narrowly defined; for other plant genera, membership is based on 
broader criteria. These differences in classification criteria may lead 
to different probabilities between genera that new exposures may occur 
when genetic material from one species in a genus is introduced into 
another species in the genus. In recent years new tools have become 
available to taxonomists, allowing them to better clarify phylogenetic 
relationships among organisms. New information, particularly that 
obtained through the use of new genetic tools, concerning organisms' 
properties and relationships may in the future alter current taxonomic 
designations. In light of these advances, EPA anticipates there may be 
some reorganizations among the Plantae, and that these 
reclassifications will better reflect the relationships

[[Page 37842]]

among plants, and the probability of new exposures in intrageneric 
crosses.
    The possibility that taxonomic classification may change as 
information accrues would add an extra layer of complexity to any 
regulations based on a taxonomic standard, and EPA probably would not 
be able to structure an exemption to accommodate for potential changes 
in classification. The possibility of reclassification also creates 
some uncertainty within the regulated community about the future status 
of a product.
    Furthermore, under the FFDCA, an exemption must be examined 
specifically within the context of the food supply and dietary 
consumption. Although some species in a genus might be food plants, 
others in that genus might not. Moreover, in a genus containing food 
plants, there may be such barriers to hybridization that some of the 
non-food species in that genus would never have contributed to the food 
supply. Thus, there may be no experience with the potential dietary 
risks associated with such non-food species. In addition, knowledge of 
whether substances such as naturally-occurring toxicants are present 
is, in general, more limited for all the plant species constituting a 
genus than it is for species used to produce the major food crops. 
Consequently, there is a greater degree of uncertainty in any finding 
applicable to all potential members of taxonomic categories. The large 
body of information supporting this exemption was generated for food 
crops in sexually compatible populations (Refs. 8, 11, 12, 13, 14, 15, 
16, 17, 18, and 19, for example). Overall, the base of dietary 
experience is not as broad or as deep for populations of plants 
described by the taxonomic standard of genus as it is for populations 
of plants described by sexual compatibility. EPA does not believe it 
possesses sufficient information at this time to allow the Agency to 
issue an exemption based on taxonomy.
    2. Sequence homology. EPA received one comment suggesting that an 
additional criterion be used to limit the concept of sexual 
compatibility. While this suggestion was made in the context of a 
comment made on the proposal to exempt plant-incorporated protectants 
derived from plants sexually compatible with the recipient plant from 
FIFRA requirements, EPA discusses that suggestion here because of its 
relevance to EPA's decision to exempt residues of pesticidal substances 
derived through conventional breeding from plants sexually compatible 
with the recipient plant. The suggested criterion of sequence homology 
would base relatedness on the degree of sequence homology between the 
source and recipient plant. Sequence homology refers to the extent that 
the sequence of deoxynucleotides in two pieces of genetic material are 
the same. A deoxynucleotide is made up of a sugar, a phosphate, and one 
of four purine or pyrimidine bases (adenine, cytosine, guanine, 
thymine). The sugars and phosphates of the deoxynucleotides are 
covalently linked by phosphodiester bonds to form the ``backbone'' of 
the deoxynucleotide polymer (DNA). One base is attached to each sugar 
in the sugar-phosphate backbone. The information encoded in the genetic 
material is determined by the sequence in which the bases are attached 
to the sugar-phosphate backbone. The extent to which two pieces of 
genetic material have the same base sequence is often described in 
terms of percent homology, with 100% homology meaning the pieces of 
genetic material have an identical sequence. The Agency currently 
believes that DNA sequence homology is a less straightforward standard 
for regulatory purposes than a standard such as sexual compatibility. 
Sexual compatibility is known in most cases, and if it is not, it is 
less burdensome and simpler to demonstrate than is relatedness based on 
DNA sequence homology. Use of homology as a criterion presents the 
following complex issues. First, where should homology be assessed? For 
example, how many genes of the source and recipient plants should be 
compared to determine the degree of homology? All the genes of both 
plants? A few genes? If only a few, which genes? Second, what degree of 
homology would be sufficient to indicate a high degree of relatedness? 
Third, under what conditions should homology be measured? Fourth, 
appropriate test procedures would need to be developed and validated in 
order to set a standard procedure for measuring homology. All of these 
issues would need to be resolved, and converted into regulatory text, 
in order to develop an exemption standard based on DNA sequence 
homology.
    3. Other potential exemptions suggested by comment. One comment 
suggested that EPA consider extending the exemption, on a case-by-case 
basis, to residues of the pesticidal substance portion of plant-
incorporated protectants derived from plants unrelated to the recipient 
plant: ``Should a gene be taken from a commonly consumed food plant and 
inserted into another commonly used food plant, and the trait is 
expressed at approximately the same (or lower) level, an exemption 
would be warranted.'' A second commenter proposed that exemptions 
should be based on a documented history of safe use.
    With regard to the suggestion that EPA consider extending 
exemptions on a case-by-case basis to residues of pesticidal substances 
of plant-incorporated protectants derived from plants unrelated to the 
recipient plant, the Agency has the option to exempt residues of 
pesticides from the requirement of a tolerance on a case-by-case basis 
provided that the residues meet the exemption standard in FFDCA section 
408(c). In addition, any person may petition EPA to establish a 
tolerance exemption pursuant to section 408(d). Section 408(d)(2)(A) 
establishes the minimum requirements for such a petition. As additional 
information becomes available, EPA will consider, in future, exempting 
from the FFDCA requirement of a tolerance, residues of plant-
incorporated protectants derived from plants unrelated to the recipient 
plant when these can be shown to meet the FFDCA section 408 safety 
standard. EPA also has the option of exempting residues of plant-
incorporated protectants based on a history of safe use where there is 
sufficient information to meet the FFDCA section 408(c) test.

IX. Statutory Finding

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

    For most pesticides (e.g., chemical pesticides), EPA's dietary risk 
evaluation relies on data generated by testing in laboratories using 
representative animal models to estimate acute, subchronic or chronic 
hazard end-points (e.g., acute toxicity, carcinogenicity, developmental 
toxicity). Conclusions from animal models are used to assess dose-
response and describe such endpoints for potential human hazard. Other 
information, including residue data and information generated by use of 
mathematical models, are used to develop human exposure estimates. 
These exposure and hazard components are combined to quantify the 
potential risk associated with the pesticide's use. Uncertainty factors 
are often used in the risk assessment to account for extrapolation from 
animal models to human toxicity and from limited studies using humans 
to the larger population. The data requirements describing the types of 
information to be generated and other guidance for assessing dietary 
risk are detailed in 40 CFR part 158.
    The questions posed as part of the risk assessment in evaluating 
residues of

[[Page 37843]]

most pesticides (e.g., chemical pesticides) can also be posed for the 
pesticide chemical residues that are the subject of this exemption, and 
40 CFR part 158 can be used as guidance in evaluating these residues 
for hazard end-points (including, for example, acute toxicity, 
carcinogenicity, and developmental toxicity). To address the hazard 
endpoints described in 40 CFR part 158 for residues of plant-
incorporated protectants derived through conventional breeding from 
sexually compatible plants, EPA relied on a very large body of 
information found, for the most part, in the public scientific 
literature. In performing the assessment for this exemption from the 
requirement of a tolerance, EPA did not need to rely as much on 
information generated from animal models as it would in assessing other 
pesticides (e.g., chemical pesticides). A very large body of experience 
with actual human dietary consumption over hundreds, if not thousands, 
of years exists for the substances that are the subject of this 
exemption. And thus, a large and varied amount of information developed 
through systematic scientific study exists in the literature, and can 
be used for assessing the risk of exempting these residues. Numerous 
epidemiological studies on humans show the health benefits of consuming 
foods containing residues of the plant-incorporated protectants that 
are the subject of this exemption (Refs. 11, 12, 13, 14, 15, 16, 17, 
18, and 19). The epidemiological studies in particular provide 
information on the effects of chronic exposure of a far longer term 
than is possible with animal model experimentation, given the large 
differences in life span between humans and most animals used in animal 
model testing. The results of many nutritional assessment studies using 
human volunteers are available on the effects of either whole foods 
from plants in sexually compatible populations or isolated constituents 
from food from such plants (Refs. 11, 12, 13, 14, 15, 16, 17, 18, and 
19). Studies have also been performed using animal models to test the 
effects of either whole foods from crops in sexually compatible 
populations or constituents from food from such crops (Refs. 11, 12, 
13, 14 15, 16, 17, 18, and 19). There is a large literature on 
constituents of food from plants in sexually compatible populations 
accumulated by a century of systematic study (Ref. 8), and EPA also 
used these sources of information.
    EPA also considered other information in the literature in 
evaluating the potential for exposure to residues of plant-incorporated 
protectants derived through conventional breeding from sexually 
compatible plants. Plant-incorporated protectants are produced within 
the living plant itself and the pesticidal substance is used in situ in 
a living plant to protect against pests, in contrast to most other 
pesticides which must be applied to the plant (Ref. 20). Because a 
plant-incorporated protectant is produced and used within the plant, 
physiological constraints limit the amounts of residues produced by the 
plant (Ref. 20). Because the plant-incorporated protectant is within 
the plant, routes by which other organisms may be exposed to the plant-
incorporated protectant may be more limited, e.g., dietary exposure is 
likely to be the predominant route of exposure.
    EPA used experimental data derived from the science of 
phytopathology to characterize the disease and pest resistance 
mechanisms known to occur in plants (Ref. 21). EPA also considered 
information from the field of plant physiology regarding plant 
metabolism, the production of substances that may have pesticidal 
effects, and conditions that may limit the plant's production of such 
substances (Refs. 7 and 20). This information also provided a basis for 
EPA's estimation of the physiological limitations to production in 
plants of substances that may be pesticidal and thus to production of 
their residues. EPA also used information from the fields of 
biochemistry, microbial ecology, and ecology (Refs. 7, 21, and 37).
    EPA's conclusion that the vast majority of plant varieties 
developed by conventional breeding in sexually compatible populations 
produce foods that are safe for human consumption is based on this 
information and the historical consumption of crops since the 
prehistorical origins of agriculture. EPA also considered its knowledge 
of the practices that plant breeders routinely employ in selecting and 
developing plant varieties in sexually compatible plant populations, 
such as chemical analyses, taste-testing, and visual analyses, and that 
such practices have historically proven reliable for ensuring the 
safety of food from such plants (Refs. 8 and 22). EPA also considered 
that appropriate processing procedures are widely known and are 
routinely used by consumers in preparation of food containing residues 
that are the subject of this exemption, including those foods which 
require specific processing and/or preparation steps to avoid dietary 
problems.
    Residues of plant-incorporated protectants derived through 
conventional breeding from sexually compatible plants were evaluated 
for dietary risk within the context of the food supply and dietary 
consumption patterns. In performing its assessment, the Agency 
considered that the diet includes all of the food items that are 
customarily eaten by human populations or subpopulations as part of a 
normal diet. (EPA did not consider that the normal diet includes plants 
or plant parts consumed in times of deprivation, for religious reasons, 
in substance abuse or by misidentification. The information base on 
which EPA relied in performing its risk assessment (Refs. 8, 11, 12, 
13, 14, 15, 16, 17, 18, and 19, for example) did not address such 
plants.)
    EPA considered health risks to the general population, including 
infants and children. Children, and to some extent infants, have always 
and currently consume food containing residues that are the subject of 
this exemption. EPA's risk assessment also included subgroups as part 
of the general population, (i.e., differences in diet due to the 
influence of culture), and allowed for consumption pattern differences 
of such subgroups. The consumption of food plants is part of a balanced 
and varied diet.
    EPA believes that the numerous epidemiological and nutritional 
assessment studies found in the literature of human experience in 
consuming food containing residues that are the subject of this 
exemption, combined with information generated from animal model 
testing and biochemical studies and knowledge from the disciplines of 
plant genetics, plant physiology, phytopathology, microbial ecology, 
ecology, biochemistry, and plant breeding form the appropriate 
information base for evaluating the potential risks of such residues.

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

    FFDCA section 408(c)(2)(B) requires EPA to consider several factors 
in determining whether to exempt a pesticide from the requirement of a 
tolerance (21 U.S.C. 346a(c)(2)(B)). Information relevant to EPA's 
consideration of these factors with regard to this exemption of the 
pesticide chemical residues of a plant-incorporated protectant derived 
through conventional breeding from sexually compatible plants, is 
contained in this document, as well as in other

[[Page 37844]]

documents in the record for this rule as described in Unit X.
    The preamble discussion in the 1994 Federal Register document (59 
FR at 60538), and in the May 16, 1997, supplemental document (62 FR 
27132), of the rationale supporting the proposal to exempt residues of 
plant-incorporated protectants derived from sexually compatible plants 
extends to any substance that is normally a component of a population 
of sexually compatible plants. It thus, applies to any substance, such 
as a selectable marker, used to confirm or ensure the presence of the 
active ingredient, that is also derived from plants sexually compatible 
with the recipient plant. EPA's analysis in Unit IX., applies equally 
to all the substances that are normally a component of a population of 
sexually compatible plants, including inert ingredients as long as 
these are derived through conventional breeding from plants sexually 
compatible with the recipient plant, and have never been derived from a 
source that is not sexually compatible with the recipient plant.
    1. Validity, completeness and reliability of available data. As 
described in Unit IX.A., EPA's risk assessment for residues of plant-
incorporated protectants derived through conventional breeding from 
sexually compatible plants was based primarily on an analysis of the 
long human experience with breeding and growing agricultural plants and 
preparing and consuming food from such plants, and associated 
epidemiological studies, nutritional assessments with human volunteers 
and animal model testing (Refs. 8, 11, 12, 13, 14, 15, 16, 17, 18, and 
19). EPA combined this information with knowledge from the disciplines 
of plant genetics, plant physiology, phytopathology, microbial ecology, 
ecology, biochemistry (including studies on the constituents of food), 
and plant breeding to evaluate the potential risks of pesticide 
chemical residues of plant-incorporated protectants derived through 
conventional breeding from sexually compatible plants. EPA considered 
the validity, completeness and reliability of the available information 
on human consumption of food containing substances that are the subject 
of this exemption including epidemiological studies, nutritional 
assessments with human volunteers and animal model testing, as well as 
information from the disciplines of plant genetics, plant physiology, 
phytopathology, microbial ecology, ecology, biochemistry (including 
studies on the constituents of food) and plant breeding. EPA concluded 
that this information was valid, complete and reliable, and adequately 
addressed the issues of hazard and exposure with regard to residues in 
food of plant-incorporated protectants derived through conventional 
breeding from sexually compatible plants.
    2. Nature of toxic effect. In light of comments raising concern 
about possible adverse effects from increases in the levels of 
substances that naturally occur at low levels in food from plants, EPA 
considered the nature of toxic effects shown by the data described in 
Unit IX.B.1., above to be caused by substances that might potentially 
be residues of plant-incorporated protectants derived through 
conventional breeding from sexually compatible plants, should these 
substances be used as pesticides (i.e., if humans intend to use these 
substances for preventing, repelling or mitigating any pest) and 
present at high levels. The examination led EPA to conclude that as the 
vast majority of substances in plants are not toxic, any of these 
nontoxic substances, should they be used as plant-incorporated 
protectants, would not present toxic effects. EPA has identified 21 
substances of plant origin that are in foods that could be considered 
part of a normal diet and could potentially present toxic effects if 
present at high levels (Ref. 8). (The normal diet does not include 
plants, or parts of plants, consumed in times of deprivation, for 
religious reasons, in substance abuse, or by misidentification. The 
normal diet is considered to be balanced and varied and include food 
from a variety of sources.) This analysis is based on an accumulation 
of millennia of human experience and a century of systematic scientific 
study of food constituents (Ref. 8). The conclusion of the analysis 
described in Unit IX.B.2., for these 21 substances indicates that they 
are either: Beyond the scope of the exemption; in foods that are not 
part of the normal diet of the United States population; and/or, 
millennia of human experience and use have given rise to procedures, on 
the part of the plant breeder, the food processor and/or the consumer, 
that combined with the condition determining eligibility for this 
exemption, adequately address the risk posed by these substances.
    These 21 substances, of the hundreds of thousands of plant-produced 
substances in food, represent less than one-tenth of 1% of the total 
number of constituents of food (Ref. 8). Of these 21 substances, seven 
(acetylandromedol, andromedol, anhydroandromedol, desacetylpireistoxin 
B, gelsamine, tutin, hyenanchin) are in honey, being ``pass-through'' 
contaminants of honey introduced by bees collecting pollen from 
rhododendron, azalea, yellow jasmine, or the tutu tree. (The substances 
from the tutu tree, tutin and hyenanchin, can cause delirium and 
convulsions). Similarly, four (cicutoxin, coiinine, methylconiine, 
conhydrine) of the 21 substances capable of causing toxic effects in 
the normal diet are pass-through contaminants in the milk of cows that 
have consumed water hemlock or hemlock. These substances are nervous 
system stimulants. None of the plant sources of these 11 pass-through 
contaminants are used or intended to be used as food plants and thus 
this section 408 exemption does not apply to them. Another of the 21 
substances in the normal diet identified as potentially causing toxic 
effects is nitrate. Exposure to excessive amounts of nitrates can cause 
methemoglobinemia, a condition in which some portion of the hemoglobin 
molecules become incapable of binding oxygen. Levels of nitrates high 
enough to cause such effects can be found in spinach and other green, 
leafy vegetables subjected to intensive application of high-nitrate 
fertilizers. Nitrates that enter the plant through uptake of fertilizer 
applied intensively are not ``produced'' by the plant per se, i.e., 
they are not biosynthesized by the plant. This exemption is not 
relevant to such nitrates. The toxic effect presented by high levels of 
nitrates is generally addressed in agriculture by use of proper 
fertilization practices.
    Of the 21 substances originally identified (Ref. 8), nine of these 
(solanine, linamarin, lotaustralin, cucurbitacin, vicine, convicine, 
hypoglycin A, sparteine, beta-N-oxalylamino-L-alanine) are 
biosynthesized by plants that could be used as food in a normal diet 
somewhere in the world, and, thus, if used by humans for pesticidal 
purposes, could potentially be pesticide chemical residues derived 
through conventional breeding from sexually compatible plants. Three of 
these nine substances (sparteine, hypoglycin A, beta-N-oxalylamino-L-
alanine) are found in food not customarily consumed as part of the 
normal diet in the United States. Their risks appear to be well known 
locally where plants containing such substances are consumed, and 
native methods of processing exist to reduce the potential for toxic 
effects (Ref. 22).
    Sparteine is a quinolizidine alkaloid found in the lupines. The 
lupines are forage or range crops, but can also be cultivated for feed 
and have some limited use in human food, primarily as

[[Page 37845]]

a ``traditional'' grain used by indigenous cultures in South America 
and the Mediterranean. The presence in the plant of the quinolizidine 
alkaloids appears to protect the plant against fungal infection. 
Reduction of the levels of quinolizidine alkaloids in the plant can 
result in increased levels of potentially more hazardous mycotoxins. 
Toxic effects from consumption of food containing higher levels of 
sparteine include breathing problems, weakness and loss of motor 
control (Ref. 22, 23). These alkaloids can be removed by cooking, or by 
rinsing for several days (Ref. 22, 24).
    Beta-N-oxalylamino-L-alanine is found in the seeds of the chickling 
vetch. It is a neurotoxin that can cause spastic paralysis, probably by 
interfering with the action of the neurotransmitter, glutamate (Ref. 
22, 25). Reported cases of toxicity are mostly confined to the Indian 
subcontinent. Most of the toxin can be leached out by soaking the seeds 
in hot water for several minutes, followed by cooking.
    Hypoglycin A is an amino acid analogue found in the immature ackee 
fruit that can result in severe hypoglycemia and vomiting. Ackee fruit 
is primarily consumed in Africa and Jamaica (Ref. 22). The primary 
method of dealing with the potential adverse effect presented by 
hypoglycin A is avoidance of (i.e., not consuming) immature ackee 
fruit.
    Of the remaining six substances, two (vicine and convicine) affect 
a small subpopulation of the United States population. Vicine and 
convicine are found in the fava bean. Exposure of individuals with the 
Mediterranean form of an inherited deficiency of the enzyme, glucose-6-
phosphate dehydrogenase (G6PD), to these substances in the fava bean 
can result in an hemolytic anemia. The anemia is manageable (Ref. 26). 
Physicians attempt to prevent hemolytic episodes by warning patients 
with the Mediterranean form of G6PD deficiency about the risks of 
consuming fava beans (Ref. 27). Thus, the primary strategy employed by 
persons with this G6PD deficiency with regard to food is avoidance of 
(i.e., not consuming) foods containing fava beans. Drying the beans or 
exposing them to sunlight reduces the potential for hemolytic episodes 
(Ref. 22).
    Several strategies, including breeding for varieties that produce 
low levels of the substances and monitoring, as well as general 
knowledge in the population, reduce the potential for toxic effects to 
occur with the remaining four toxicants (cucurbitacin, linamarin, 
lotastralin, solanine). Cucurbitacins are naturally present in edible 
squash and cucumbers at very low levels. Cucurbitacins are purgatives 
and impart a bitter taste to the fruit. Cucurbitacins if consumed at 
extremely high concentrations may cause stomach aches or cramps (Refs. 
22 and 28). On rare occasions, in producing seed for cultivated 
varieties, pollen from a wild relative may contaminate the seed plot, 
resulting in seeds that may produce higher levels of cucurbitacin. 
Breeding isolation is employed by seed producers to ensure that such 
contamination does not occur (Refs. 7 and 22).
    Linamarin and lotaustralin (also called phaseolutin) are cyanogenic 
glycosides (Refs. 8 and 22) biosynthesized by cassava and lima beans. 
When the plant tissue is damaged, enzymes are released that act on the 
cyanogenic glycoside to produce hydrogen cyanide. The toxicity of 
cyanide is due to its ready reaction with the iron atom of the enzyme, 
cytochrome oxidase. The ability of the cell to utilize oxygen is 
inhibited by formation of the cytochrome oxidase-cyanide complex. Toxic 
effects associated with cyanide include neurological disorders, 
breathing difficulties, and thyroid enlargement (Ref. 22). The lima 
bean varieties on the United States market today were bred and are 
monitored to ensure that they produce very low levels of cyanogenic 
glycosides (Refs. 22 and 29). Imported lima beans are monitored to 
ensure only low levels of cyanogenic glycosides (Refs. 22 and 29). 
Similarly, cassava used in the United States today comes from varieties 
that were bred and are monitored to ensure that they produce very low 
levels of cyanogenic glycosides. Populations outside of the United 
States (e.g., Africa) that consume cassava from varieties that produce 
higher levels of cyanogenic glycoalkaloids are aware of the risk 
associated with this food and use native methods of processing 
(peeling, chopping and grinding in running water, also boiling and 
fermentation) to reduce the cyanogenic glycoside content. Cases of 
toxicity are observed primarily in these populations when the cassava 
is eaten without adequate processing, because a scarcity of other food 
items causes individuals to risk consuming inadequately processed 
cassava to ease their hunger (Ref. 26). There are also ongoing breeding 
and monitoring efforts to assist these populations to reduce the 
cyanogenic glycoside content in cassava varieties grown in their 
countries.
    The glycoalkaloids collectively referred to in this document as 
solanine are biosynthesized by potatoes, and to some extent eggplant 
and peppers. A related glycoalkaloid, tomatine, can be found in green 
tomatoes. The solanines are membrane disruptors. Some members of the 
class have been shown in vitro and through intraperitoneal and 
intravenous injection to be weak to moderate cholinesterase inhibitors 
(Ref. 30). While solanine poisoning is very rare, in large doses 
solanine can cause gastrointestinal tract irritation, including 
moderate nausea, vomiting and diarrhea, as well as headaches, 
drowsiness, sweating, changes in blood pressure and heart rate, and 
edema (Ref. 22). Solanine imparts a bitter taste to the tuber, and at 
high concentrations solanine can leave a persistent irritation and 
burning sensation on the tongue (Ref. 22). Potato varieties are bred 
and monitored in the United States to ensure that they produce only low 
levels of solanine (Refs. 22 and 31). Monitoring for these 
glycoalkaloids also occurs during the grading and shipping of potatoes. 
Peeling or removing any damaged portion of the potato is the best way 
to reduce solanine levels. In an undamaged, unsprouted potato, thirty 
to eighty percent of the solanine is found in, and directly under, the 
skin. Cooking, e.g., boiling in steam or water or deep frying in oil at 
170 degrees, may lower solanine concentrations (Refs. 22 and 32).
    For the reasons described in the preceding paragraphs, EPA does not 
believe that this exemption would result in levels in food of residues 
of these four substances significantly different from those observed in 
food currently safely consumed. That there have been few instances in 
the United States of toxic effects on humans due to substances normally 
found in food from plants in sexually compatible populations in the 
past 50 years, despite the hundreds of food plant varieties from 
sexually compatible plant populations going onto the market each year 
(Ref. 8), supports a conclusion that the probability of risk is low 
even for the few substances discussed in this Unit. As an added 
protection, EPA has placed a condition limiting the exemption to 
residues present in food from the plants at levels that are not 
injurious or deleterious to human health.
    3. Relationship of studies to humans. EPA considered the available 
information concerning the relationship to human risk of this 
information on residues in food of plant-incorporated protectants 
derived through conventional breeding from sexually compatible plants. 
The effect of these residues on humans was assessed in light of the 
long history of human

[[Page 37846]]

consumption of food derived from plants, and from products such as meat 
and milk from animals that consume forage and other crops (e.g., corn 
and other grains), containing residues that are the subject of this 
exemption, and associated epidemiological studies, nutritional 
assessments with human volunteers and animal model testing (Refs. 8, 
11, 12, 13, 14, 15, 16, 17, 18, and 19). The epidemiological studies 
and nutritional assessments performed with human volunteers supply data 
generated on humans and, thus, directly applicable to humans. 
Information from animal model testing as well as information from the 
disciplines of plant genetics, plant physiology, phytopathology, 
microbial ecology, ecology, biochemistry (including studies on the 
constituents of food) and plant breeding were also used to predict 
effects on humans. Because information on human consumption of food 
derived from plants comprising sexually compatible populations was 
available and adequately addressed the issues of hazard and exposure 
for residues that are the subject of this exemption, the Agency relied 
primarily on the epidemiological and other information generated 
directly from humans rather than relying on data generated in the 
laboratory through animal testing.
    4. Dietary consumption patterns. EPA considered the available 
information on the varying dietary consumption patterns of consumers 
and major identifiable consumer subgroups as it pertains to residues 
that are the subject of this exemption. The consumption of food from 
plants is part of a balanced and varied diet (Ref. 33). Humans have 
been consuming food containing substances that may be residues of 
plant-incorporated protectants derived through conventional breeding 
from sexually compatible plants and thus, all consumers, and all major 
identifiable consumer subgroups, are, and have been, exposed to the 
substances that are the subject of this exemption. It is not 
anticipated that publication of this exemption from the requirement of 
a tolerance will affect current consumption patterns of food from crop 
plants by consumers or major identifiable consumer subgroups, and thus 
no differences in exposure patterns are anticipated.
    5. Available information concerning cumulative effects of the 
pesticide chemical residue and other substances that have a common 
mechanism of toxicity. EPA examined available information on the 
cumulative effect of residues of plant-incorporated protectants derived 
through conventional breeding from sexually compatible plants, as well 
as other substances present in food that may have a common mechanism of 
toxicity with such residues.
    i. What information is available on the cumulative effects of the 
residues that are the subject of this exemption? A large amount of 
information exists for the residues that are the subject of this 
exemption. The extensive information described in Unit IX.A. and Unit 
IX.B.1., e.g., epidemiological studies, nutritional assessment studies 
and animal model testing (Refs. 11, 12, 13, 14, 15, 16, 17, 18, and 19) 
indicates a very low probability of harm. The few substances occurring 
naturally in food from plants that EPA has identified as being 
problematic are discussed in Unit IX.B.2. A discussion of the variation 
in the levels of substances that may be pesticide chemical residues and 
may occur naturally among the plants of a sexually compatible 
population, and the potential consequences of that variation are 
discussed in Unit IX.B.6.
    If information becomes available that indicates its analysis of 
cumulative effects in Unit IX.B.5., is no longer consistent with the 
FFDCA exemption standard for residues of a pesticidal substance in this 
category, EPA will consider the validity of the new information and may 
act to amend this tolerance exemption.
    ii. Are there substances that occur naturally in food that may 
share a common mechanism of toxicity with residues that are the subject 
of this exemption? Because of the conditions of this exemption, i.e., 
the genetic material leading to the production of the plant-
incorporated protectant is derived through conventional breeding from 
plants sexually compatible with the recipient plant, the potential for 
new dietary exposures is low. Thus, EPA considered the effects of all 
the substances in food from plants when it addressed the safety of food 
from plants in sexually compatible populations, including those that 
occur naturally in plants along with the substances that are the 
subject of this exemption. Food from plants has hundreds of thousands 
of constituents, and EPA cannot rule out the possibility that in the 
foods humans consume, common mechanisms of action might exist between 
some of these substances and the various residues that are the subject 
of this exemption. For example, the word ``solanine'' generically 
refers to a group of related steroid glycoalkaloids that naturally 
occur in plants in the nightshade family such as potatoes, eggplant, 
peppers and green tomatoes. EPA's analysis considered the effects of 
these substances in food from plants cumulatively when it addressed the 
safety of food from plants in sexually compatible populations.
    Food from plants in sexually compatible populations is being safely 
consumed by humans either directly, or indirectly in products such as 
meat and milk that are derived from animals that consume forage and 
other crops (e.g., corn and other grains). The history of safe 
consumption and the information base described in Unit IX.A. and Unit 
IX.B.1. indicates that any cumulative effects between substances in 
food that may have a common mechanism with residues that are the 
subject of this exemption present a very low probability of harm. The 
analysis made in this preamble in Unit IX.B.6., concerning potential 
increases in levels of residues apply equally to constituents of food 
that may have a common mechanism of action with residues that are the 
subject of this exemption. Variations in the levels of these substances 
are not expected to be any different than those currently observed in 
conventional breeding. Experience has shown that food from crop plants 
in sexually compatible populations is safe for human consumption and/or 
appropriate processing procedures are widely known and routinely used 
by processors and consumers in preparing food from such sources. Should 
EPA in the future identify substances with a common mechanism of 
toxicity with the residues that are the subject of this exemption, both 
FIFRA and the FFDCA give the Agency adequate authority to take 
appropriate action to address any risks these substances may present to 
human health. Should substances in food that may share a common 
mechanism of toxicity with residues that are the subject of this 
exemption present cumulative effects resulting in food safety concerns, 
the condition limiting this exemption at 40 CFR 174.479 and the 
requirement to report adverse effects at Sec. 174.71 will provide a 
mechanism to monitor the effects of this class of products and allow 
the EPA and FDA to act expeditiously.
    iii. Are there substances that do not occur naturally in food that 
may share a common mechanism of toxicity with residues that are the 
subject of this exemption? EPA examined two groups of substances to 
determine whether these substances have a common mechanism of toxicity 
with residues that could be the subject of this exemption.
    a. Do the organophophate and carbamate pesticides have a common 
mechanism of toxicity with the naturally occurring toxicants solanine? 
EPA examined certain of the

[[Page 37847]]

organophosphate and carbamate pesticides and the naturally-occurring 
toxicants, solanine (described in Unit IX.B.2.). EPA examined these 
substances because many members of these two classes of pesticides 
inhibit the cholinesterase enzymes (Refs. 30 and 34), and some in vitro 
and intraperitoneal and intravenous injection studies have shown that 
some of the glycoalkaloids comprising the solanines also can inhibit 
these enzymes (Refs. 22 and 30). The solanines have also been shown to 
disrupt cell membranes (Ref. 30).
    EPA examined available information generated both in vitro and 
through in vivo animal studies on solanine. EPA gave greater weight in 
its analysis to information generated by animal studies where the 
animals were exposed through oral ingestion, as such studies are far 
more likely to provide physiologically significant information. Animal 
studies performed with the solanines administered to the animals in 
similar manner that plant-incorporated protectants would be presented 
in the diet (i.e., through ingestion) show that death could not be 
attributed to cholinesterase inhibition and its neurotoxic consequences 
but was due to severe gastrointestinal necrosis from cell membrane 
disruption (Ref. 35).
    Given this information, EPA has concluded that available 
information is insufficient to create a presumption of the existence of 
a common mechanism of toxicity between solanine and the organophosphate 
and carbamate pesticides (Ref. 36), particularly as animal studies 
suggest the solanines, when used as plant-incorporated protectants, 
lead to the endpoint of death through membrane disruption.
    b. Do microorganisms have metabolic pathways in common with plants? 
One commenter, in response to the May 16, 1997, supplemental document, 
suggested that some microorganisms may have some metabolic pathways in 
common with plants, although the commenter was of the opinion that this 
is not likely to be problematic. EPA agrees that this route of exposure 
to any substances that may be related to residues that are the subject 
of this exemption is unlikely to be problematic, and notes that 
possession of the same metabolic pathways does not equate to expression 
of the same characteristics. Raw plant foods commonly contain hundreds 
to several million microorganisms per gram (Ref. 8). Some of these 
microorganisms are commensals of the plant, others come from the 
natural environment of the plant (e.g., soil, water, air, other 
plants). Such microorganisms are routinely consumed with raw 
agricultural produce. Certain microorganisms are deliberately consumed 
routinely in high numbers by humans with no ill effects (e.g., Marmite 
based on a yeast, natto based on the bacterium Bacillus subtilis, 
yogurt made with bacteria of the genus Lactobacillus, cheese made with 
the fungus Penicillium roquefortii). This base of experience with 
actual human consumption indicates that should such microbes have any 
metabolic pathways in common with foodstuffs from plants, the 
cumulative effect of substances from these pathways with residues that 
are the subject of this exemption, presents a very low probability of 
harm.
    c. Are there any other substances? EPA cannot rule out the 
possibility that there may be other substances outside of the food 
supply that may have a common mechanism of toxicity with the residues 
that are the subject of this exemption, although it is not aware of any 
other such substances. Should EPA in future identify substances with a 
common mechanism of toxicity other than those found in food plants, 
both FIFRA and the FFDCA give the Agency adequate authority to take 
appropriate action.
    6. Aggregate exposures of consumers including non-occupational 
exposures. EPA considered the available information on the aggregate 
exposure level of consumers to the residues of plant-incorporated 
protectants derived through conventional breeding from sexually 
compatible plants, including exposure to these substances in plants 
when they are not intended to be used as plant-incorporated protectants 
(i.e., when humans are not intending to use the substance for a 
pesticidal purpose). This evaluation included a consideration of 
exposures from dietary sources as well as from other non-occupational 
sources. Plant-incorporated protectants and their residues are likely 
to present a limited exposure to humans. In most cases, the 
predominant, if not the only, exposure route will be dietary. Exposure 
through other routes is likely to be negligible because the substances 
are in the plant tissue and thus are found either within the plant or 
in close proximity to the plant.
    In addition, the substances evolved by populations of sexually 
compatible plants are part of the metabolic cycles of these plants. 
These substances are biotic and are subject to the processes of 
biodegradation and decay that all biotic materials undergo (Ref. 37). 
Biotic materials are broken down to constituent parts through the 
enzymatic processes of living organisms, and these constituent parts 
used as the building blocks to make other biotic substances.
    Because of their biodegradable nature, the residues that are the 
subject of this exemption do not bioaccumulate (bioaccumulation occurs 
when a substance is taken into the body through processes such as 
eating, and as the body is unable to either break the substance down or 
eliminate it, the substance accumulates in the tissues) or biomagnify 
in the tissues of living organisms (biomagnification occurs when a 
substance bioaccumulates in the bodies of organisms lower in the food 
chain, and as predators higher in the food chain consume organisms 
lower in the food chain, more and more of the substance accumulates in 
the bodies of organisms higher in the food chain) as do such long-lived 
persistent substances such as DDT (Ref. 38). Humans ingesting the 
substances that are the subject of this exemption are likely to quickly 
degrade them and use their constituent elements as nutrients. Because 
of these characteristics, the potential for exposures to the residues 
to occur, beyond direct physical exposure to, or consumption of, the 
plant, is limited. This also contributes to EPA's conclusion that non-
dietary exposure (i.e., non-food oral, dermal and inhalation) in non-
occupational settings is likely to be negligible.
    i. Dietary exposures? As described in Unit IX.A. and Unit IX.B.1., 
a large base of experience exists, including information on human 
dietary exposure, for the residues exempted by this action. Moreover, 
dietary exposures other than those for which a large base of 
information exists, are unlikely to result from this exemption for 
residues of plant-incorporated protectants derived through conventional 
breeding from sexually compatible plants. Plants in a sexually 
compatible population are likely to have similar genetic information 
and have many traits in common. Generations of directed breeding to 
produce improved crops for cultivation have tended to increase the 
relatedness, and reduce the genetic variability, of populations of 
agricultural crop plants (Ref. 6). Sexually compatible plants share a 
common pool of genetic material, and movement of genetic material 
encoding pesticidal substances between plants in a sexually compatible 
population through conventional breeding is unlikely to result in 
exposure of humans consuming food from such plants to residues to which 
no humans previously has been exposed and to which the information base 
underlying this exemption cannot be applied. The SAP Subpanel and the 
BSAC

[[Page 37848]]

Subcommittee at the joint meeting held on January 21, 1994, supported 
this conclusion and noted that genetic mapping of the genomes of both 
wild and crop plants reinforce the thesis that plants in sexually 
compatible populations are likely to possess similar genetic 
information (Ref. 6). It is likely that substances that are the subject 
of this exemption are present at low concentrations in the edible parts 
of plants, and that such substances have long been part of the human 
diet. There is no evidence at present in the many studies performed on 
the relationship of diet to health that food from plants in sexually 
compatible populations, properly handled, has any significant adverse 
health effect (Refs. 8, 11, 12, 13, 14, 15, 16, 17, 18, and 19).
    The primary exposure consideration associated with the substances 
that are the subject of this exemption is whether the substances, 
identified in Unit IX.B.2. as toxic at higher concentrations, are 
likely to be present in food from plants in sexually compatible 
populations at such concentrations. EPA carefully examined whether 
there are variations, within and among food plant varieties in sexually 
compatible plant populations, in levels of plant-incorporated 
protectants and thus in the residues that are the subject of this 
exemption from the FFDCA requirement of a tolerance (Ref. 20). The 
amount of any substance produced by plants normally varies among 
members of a sexually compatible plant population because of the 
effects of conditions such as genetic constitution and environment 
(e.g., weather) (Refs. 8 and 20). Indeed, such variation is observed 
among plants of the same variety. For example, one researcher (Ref. 8) 
has shown a 20-fold variation in the amount of ascorbic acid (3 to 61 
mg/100g tissue) in different varieties of muskmelon. Because such 
variation is ubiquitous in populations, differences in the levels of 
exposure to substances in plants are likely when humans consume food 
from plants, including differences in exposure to residues that are the 
subject of this exemption. Such variation is a natural phenomenon 
common to all plants, however, in controlled food production the 
variation in the substances identified in Unit IX.B.2. is limited (Ref. 
22).
    EPA also examined whether the levels of substances any variety 
within a sexually compatible population could produce are likely to 
exceed the range of low concentrations found in crop plant varieties 
safely consumed. For the following reasons, the Agency concluded that 
such occurrences were unlikely. First, there are several constraints on 
the extent to which expression of any substance can be increased in 
highly managed food crop plants without unwanted effects on other, 
desirable characteristics of the plant such as yield or palatability. 
In general, breeders balance a number of characteristics (e.g., yield, 
palatability, height, uniformity of seed drop) in developing marketable 
plant varieties. Solanine and cucurbitacin, for example, affect 
palatability as they taste bitter to humans.
    Moreover, in conventional breeding, plant breeders assess the new 
cultivar for food safety, based in part on knowledge of and familiarity 
with the characteristics of agricultural plants in sexually compatible 
populations (Ref. 22). EPA's assessment of the likelihood of breeders 
ensuring that plants developed through conventional breeding will 
continue to be safe for consumption is supported by the record of 
safety of the food products from plants in sexually compatible 
populations. Although hundreds of new varieties come on the market each 
year, within the past 50 years, conventional plant breeding of plants 
in sexually compatible populations has recorded very few instances of 
plant varieties causing food safety problems. The two identified 
instances (Ref. 8), high psoralen expressing celery that in the 1980s 
caused dermatitis in grocery employees and the Lenape potato in the 
late 1960s with increased glycoalkaloid levels, involved increases in 
the level of known toxicants (which may or may not be plant-
incorporated protectants depending on whether humans intend to use 
these substances for preventing, destroying, repelling or mitigating 
any pest). In both cases, the problem was identified and the 
appropriate measures taken to protect the public health. In the case of 
the Lenape potato, food processors in routine screening detected the 
high levels of solanine and the potatoes were removed from the market 
before exposure of consumers (Ref. 8). In contrast to these few 
problematic occurrences, there are many studies indicating the health 
benefits of consuming plant foods that likely contain residues that are 
the subject of this exemption (Refs. 8, 11, 12, 13, 14, 15, 16, 17, 18, 
and 19).
    A second exposure consideration is whether this exemption will 
affect the ability of individuals with food sensitivities to manage 
these sensitivities. To protect themselves, individuals with food 
sensitivities generally avoid the food, and related foods, that cause 
them problems (Ref. 39). This exemption will not affect the efficacy of 
this strategy of avoidance, because the exemption will not affect the 
ability of individuals to recognize and avoid foods that cause them 
problems (Refs. 27, 39, and 40). For example, the ability of persons 
who have the Mediterranean form of the inherited G6PD deficiency to 
deal with their disease by avoiding (i.e., not consuming) fava beans or 
foods made with fava beans will not be affected. The substances in fava 
beans that can cause hemolytic anemias in such persons will be exempt 
only if they are moved through conventional breeding among fava bean 
plants and plant varieties sexually compatible with fava beans; a 
population of plants in which such substances normally occur, and the 
food of which individuals with the inherited G6PD deficiency avoid 
(Ref. 27). Similarly, the efficacy of the strategy of avoidance will 
not be affected for individuals suffering from food allergy (Ref. 39) 
or enteropathies such as celiac disease (gluten-sensitive enteropathy) 
(Ref. 40). Moreover, the efficacy of the monitoring, processing, and 
preparation methodology which humans are familiar with and have been 
adequate in the past to produce food safe for consumption will not be 
affected by publication of the exemption, e.g., the monitoring 
procedures for solanine used in the breeding and marketing of potatoes.
    EPA believes the history of familiarity with agricultural plants in 
sexually compatible populations, and thus with the likely progeny of 
genetic exchanges between plants in such populations (Ref. 8), and the 
procedures currently employed in plant breeding to screen out 
undesirable traits in such populations, support a tolerance exemption 
for residues of plant-incorporated protectants derived through 
conventional breeding from sexually compatible plants. However, to 
ensure that the Agency can act expeditiously should any rare instances 
of risk arise, EPA is placing at 40 CFR 174.479 a condition on this 
exemption from the requirement of a tolerance limiting the 
concentrations in food of substances such as toxicants that may be 
injurious or deleterious to human health. EPA is also implementing an 
adverse effects reporting requirement at Sec. 174.71 that will serve to 
alert the Agency to any such rare instances of risk.
    One comment received in response to the May 16, 1997, supplemental 
document (62 FR 27132), suggested that plant extracts might be used in 
some pharmaceutical preparations. The commenter did not provide any 
examples of these types of situations, nor any information on such 
extracts. Without such additional information, it

[[Page 37849]]

is difficult to determine whether the extracts would contain substances 
related to residues that are the subject of this exemption. However, 
even if such related substances are present in some pharmaceutical 
preparations, on a per person basis, the potential amounts involved in 
these exposures are likely to be a negligible contribution to aggregate 
exposure. The commenter also was of the opinion that such uses are not 
likely to be problematic.
    ii. Dermal exposure. With regard to the dermal route of exposure, 
residues of plant-incorporated protectants derived through conventional 
breeding from sexually compatible plants may in some cases be present 
in sap or other exudates from the plant or the food and thus may 
present some limited opportunity for dermal exposure to persons coming 
physically into contact with the plant or raw agricultural food from 
the plant. Individuals preparing meals are those most likely to 
experience dermal contact with the substances on a non-occupational 
basis. Although contact dermatitis can occur from such exposure (Refs. 
41 and 42), these reactions are generally mild, of a self-limiting 
nature or self-diagnosed and treated.
    Most of the substances that could be the subject of this exemption 
are unlikely to pass through the skin to affect other organ systems 
(Refs. 41, 42, and 43). For those substances which possess to some 
degree properties that allow some penetration of the skin, the 
potential amounts of such exposures, on a per person basis, are likely 
to be a negligible contribution to aggregate exposure, or do not 
present adverse effects.
    There are a few substances with the ability to present an effect on 
dermal exposure on a non-occupation basis, that might be residues of 
plant-incorporated protectants, if humans intend to use these 
substances as pesticides. For example, one substance present in a food 
(condiment) Americans might use in preparing meals and identified as a 
potential skin irritant (Refs. 8 and 22) is the phenolic, capsaicin, 
found in cayenne pepper. Capsaicin is used medically in a topically 
applied cream, which facilitates passage of the capsaicin across the 
barrier of the outer layer of the skin, at concentrations of 0.025 to 
0.075% capsaicin. The cream is applied up to four times daily for pain 
control and treatment of psoriasis (Refs. 22 and 44). Cayenne pepper 
can be used liberally in the diet. Currently, cayenne pepper is exempt 
from the requirement of tolerance when it is used on food crops (40 CFR 
180.1165). Acute toxicity through the oral route has been examined in 
several animal species, and it is estimated that the lethal dietary 
dose for a 150 pound individual is 2.2 kilograms (Refs. 22 and 45). 
Given the low toxicity of capsaicin, even if capsaicin should penetrate 
through the barrier of the skin, aggregate exposure through the dermal 
and dietary routes is not anticipated to present harm.
    A second substance examined because of known effects beyond mild 
dermatitis with dermal exposure are the psoralens. These substances 
occur naturally in a wide range of plants but occur in the highest 
concentrations in celery, dill and parsley (Refs. 22 and 41). Psoralens 
can be phototoxic to the skin in conjunction with sunlight (UV light). 
Due to their relative solubility in oils, psoralens can penetrate into 
the skin cells, where they intercalate into the genetic material of the 
skin cell (Refs. 22 and 41). Subsequent exposure to sunlight (UV light) 
causes the genetic material to ``cross link,'' affecting the ability of 
the cell to further process its genetic material. This may result in 
skin blisters and rashes. This UV-dependent phototoxicity has also been 
implicated in mutations that may lead to skin cancer (Refs. 22 and 41). 
In spite of the potential for this type of adverse effect with the 
psoralens, there are few reported incidents for substances derived 
through conventional breeding from sexually compatible plants (Ref. 8).
    Psoralens (supervised and in small doses) are also used in the 
treatment of a variety of skin diseases, including vitiligo and 
psoriasis (Ref. 22), primarily through topical application.
    The primary route through which humans in general are exposed to 
psoralens is dietary, and the psoralens are not toxic when ingested. 
Given the low oral toxicity, the supervised use of psoralen in 
medicine, the low concentrations of psoralen in celery, dill and 
parsley currently on the market, and the condition EPA has placed on 
this exemption limiting the amount of substances in food that may have 
an injurious or deleterious effect on human health, EPA finds that for 
psoralen, were this substance to be used as a plant-incorporated 
protectants derived through conventional breeding from sexually 
compatible plants, there is a reasonable certainty that no harm will 
result from aggregate exposure.
    Those few substances from food plants discussed in Unit IX.B.2., 
which might be present in foods Americans might use in preparing meals 
and which at higher concentrations can cause adverse effects, do so 
when ingested (Refs. 22, 26, 29, and 31). Substances that are the 
subject of this exemption are unlikely to pass through the skin to 
affect target organs. For those substances which possess to some degree 
properties that allow some penetration of the skin, the potential 
amounts of such exposures, on a per person basis, are likely to be 
negligible in comparison to potential exposure through the dietary 
route, or do not cause adverse effects. Dermal exposures are, thus, 
unlikely to contribute significantly to aggregate exposure.
    One comment received in response to the May 16, 1997, supplemental 
document (62 FR 27132) suggested that plant extracts might be used in 
some cosmetic preparations. The commenter was of the opinion that such 
uses are not likely to be problematic. The commenter did not provide 
any examples of these types of extracts, nor any information on the 
source or composition of such extracts. Without such additional 
information, it is difficult to determine whether the extracts would 
contain substances related to residues that are the subject of this 
exemption. EPA is aware that some floral extracts are used in perfumes, 
e.g., lavender, jasmine, rose. However, lavender, jasmine and rose are 
not generally consumed as staple foods, although parts of these plants 
can be brewed into teas or tisane. The amounts ingested through the 
tisane or by passing through the skin from perfumes is likely to be 
very small. Further, EPA is not aware of any reports of adverse effects 
from use of these flowers in tisane or perfumes. Even if such 
substances are present in some cosmetic preparations, on a per person 
basis, the potential amounts involved in these exposures are likely to 
be negligible.
    EPA is also aware of other extracts used in perfumes from plants 
consumed as food, e.g., carrot, fennel, garlic, lemon. Even if such 
substances are present in some cosmetic preparations, on a per person 
basis, the potential amounts involved in these exposures are likely to 
be a negligible contribution to potential exposure through the dietary 
route.
    iii. Inhalation exposure. With regard to exposure through 
inhalation, residues of plant-incorporated protectants derived through 
conventional breeding from sexually compatible plants may in some cases 
be present in pollen and some individuals (e.g., those living or 
working near enough to farms, nurseries or other plant-growing areas to 
be exposed towind-blown pollen, or visiting such areas) may be exposed, 
through inhalation, to the pollen. On a per person basis, the potential 
amounts of pollen involved in these exposures are likely to be 
negligible in comparison

[[Page 37850]]

to potential exposure through the dietary route. Residues of the 
pesticidal substance will not in every case be present in the pollen. 
When present in pollen, the residues are likely to be integrated into 
the tissue of the pollen grain. Pollen grains are solid, insoluble 
particles of sufficiently large diameter that they are filtered out in 
the nasopharynx or in the upper respiratory tract (Refs. 41 and 46). 
This exemption will not change current exposures nor affect strategies 
for dealing with residues that are the subject of the exemption. (Ref. 
41).
    iv. Drinking water. EPA also evaluated potential non-occupational 
exposures in drinking water. The substances in plants or parts of 
plants, including residues of plant-incorporated protectants derived 
through conventional breeding from sexually compatible plants, are 
produced and used inside the living plant itself. The residues are part 
of the living tissue of the plant. When the plant dies or a part is 
removed from the plant, microorganisms colonizing the tissue 
immediately begin to degrade it, using the components of the tissue 
(including any residues that are the subject of this exemption in the 
tissue) as building blocks for making their own cellular components or 
for fueling their own metabolisms. The residues that EPA is exempting 
in this action, including those identified at Unit IX.B.2., as toxic at 
higher concentrations, are subject to the same processes of 
biodegradation and decay that all biotic materials undergo. This 
turnover of biotic materials in nature through a process of 
biodegradation occurs fairly rapidly (Ref. 37). There is no indication 
that naturally-occurring plant biotic materials, including the residues 
that are the subject of this exemption, are resistant to 
biodegradation. Because of the fairly rapid turnover of these residues, 
even if they reach surface waters (through pollen dispersal or parts of 
the plants (leaves, fruits etc.) falling into bodies of water), they 
are unlikely to present anything other than a negligible exposure in 
drinking water drawn either from surface or ground water sources.
    v. Residential exposure. EPA is not aware of any residential uses 
of plant-incorporated protectants that might result in exposure to 
residues that are the subject of this exemption.
    7. Sensitivities of subgroups. EPA considered available information 
on the sensitivities of subgroups as it pertains to residues of plant-
incorporated protectants derived through conventional breeding from 
sexually compatible plants. In performing its assessment, the Agency 
considered that the diet includes all of the food items that are 
customarily eaten by human populations or subpopulations. As discussed 
in this preamble, this exemption will not affect the current pattern of 
exposure to residues that are the subject of this exemption. 
Individuals recognize and are familiar with the plant-derived food they 
consume, and, based on prior experience with food, individuals avoid 
consuming foods containing substances they know, either through 
personal experience or through acquired knowledge, cause them problems 
(Refs. 8, 39, and 40). Because the exposure pattern will not be 
affected by publication of this exemption, the efficacy of the current 
strategy whereby sensitive individuals recognize and avoid foods known 
to cause them problems will not be affected by this exemption (Ref. 39, 
40). For example, the ability of persons who have the Mediterranean 
form of the inherited G6PD deficiency to deal with their disease by 
avoiding (i.e., not consuming) fava beans will not be affected. Thus, 
no subgroup should be adversely affected by the exemption.
    8. Estrogenic or other endocrine effects. While there is some 
information on estrogenic effects from exposure to certain pesticides, 
the data are limited. It is known that certain food plants (e.g., 
soybeans) contain estrogen mimics, termed phytoestrogens. Such 
phytoestrogens are currently being consumed by humans in food derived 
from plants and are part of the extensive history of safe human 
consumption of food from plants. Although no information was submitted 
to EPA on this issue despite the Agency specifically soliciting it in 
the May 16, 1997, supplemental document (62 FR 27132), EPA cannot rule 
out the possibility that such phytoestrogens could be used as plant-
incorporated protectants. Potential exposure of humans via consumption 
of plant tissue to phytoestrogens exerting estrogenic effects and used 
as plant-incorporated protectants may need to be considered as EPA 
examines the issue of endocrine disruptors. If dietary exposure to 
phytoestrogens (that are also plant-incorporated protectants) is 
discovered to be a significant factor, the Agency will re-examine this 
exemption from the requirement of a tolerance in light of that 
information.
    9. Safety factors. EPA did not rely solely on available animal data 
in reaching its determination that residues of plant-incorporated 
protectants derived through conventional breeding from sexually 
compatible plants can be exempted from the requirement of a tolerance. 
There is a long history of safe human consumption of food containing 
residues that are the subject of this exemption, and of food derived 
from animals that consume forage and other crops containing these 
residues (e.g., corn and other grains). EPA thus was able to rely on 
epidemiological studies on humans, nutritional assessments with human 
volunteers and animal model testing generated through a century of 
systematic scientific study and available in the public literature 
(Refs. 8, 11, 12, 13, 14, 15, 16, 17, 18, and 19). EPA also relied on 
knowledge from the disciplines of plant genetics, plant physiology, 
phytopathology, microbial ecology, ecology, biochemistry (including 
studies on plant constituents) and plant breeding. EPA believes that 
long-term evidence of human consumption and the large base of 
scientific data generated by epidemiological studies on humans and 
nutritional assessments with human volunteers, with a more limited 
reliance on animal experimentation data, is the appropriate information 
for evaluating whether residues of plant-incorporated protectants 
derived through conventional breeding from sexually compatible plants 
warrant exemption. Because EPA was able to rely on data from humans, 
the Agency concluded that a safety factor designed to account for 
uncertainties in extrapolating from animal data would not be necessary. 
In addition, because the available epidemiological and other 
information generated on humans was based on studies employing very 
large numbers of individuals, the Agency concluded that a ten-fold 
safety factor to account for uncertainties in analyzing the human data 
would not be necessary.
    10. Infants and children. EPA considered available information on 
consumption patterns of infants and children, including special 
sensitivity, cumulative effects of residues of plant-incorporated 
protectants derived through conventional breeding from sexually 
compatible plants with other substances that may have a common 
mechanism of toxicity with these residues, and the need for a margin of 
safety for infants and children.
    i. Dietary consumption patterns. EPA considered available 
information on the dietary consumption pattern of infants and children 
as pertains to residues of plant-incorporated protectants derived 
through conventional breeding from sexually compatible plants. The 
range of foods consumed by infants and children is in general more 
limited than the range of foods consumed by adults. Most newborns rely 
on milk products for nutrition, although some infants are fed

[[Page 37851]]

soy-based products. Soy-based products may contain residues that are 
the subject of this exemption. Infants begin as early as four months of 
age to consume specific types of solid foods from plants that may 
contain residues that are the subject of this exemption. Subsequent to 
four months of age, apart from processing to facilitate swallowing, the 
diets of infants begin to be based on foods consumed by the general 
adult population albeit in different proportions. As infants and 
children mature, more and more of the foods normally consumed by adults 
become part of their diets and the relative proportions of the 
different types of food consumed changes to more closely resemble an 
adult diet. The substances that are the subject of this exemption occur 
in the normal diet. They have been consumed by infants and children 
over very long periods of time and currently are being consumed by 
infants and children. Exposure as part of a normal diet to these 
substances is highly unlikely to lead to harm to infants and children. 
As the diets of humans change from infancy through childhood and into 
adulthood, there is some possibility that the amount of the substances 
that are the subject of this exemption being consumed may change with 
those consuming the greatest amounts of food of plant origin receiving 
the highest exposure to substances that are the subject of this 
exemption. There is no evidence that such changes are likely to result 
in disproportionately high consumption of these residues in comparison 
to the general population. The evidence strongly suggests that 
consumption of foods containing the substances that are the subject of 
this exemption, including changes in exposure because of changes in the 
relative proportions of the different types of food consumed from 
infancy through childhood and into adulthood, is highly unlikely to 
lead to any harm.
    ii. Special susceptibility. EPA considered available information on 
the potential for special susceptibility of infants and children, 
including prenatal and postnatal toxicity, to residues of plant-
incorporated protectants derived through conventional breeding from 
sexually compatible plants. The substances that are the subject of this 
exemption occur in the normal diet, and there is no evidence that 
exposure to such residues, as components of food, present a different 
level of dietary risk for infants and children, in light of 
neurological differences between infants and children and adults, than 
they would present for the adult population.
    iii. Cumulative effects of residues with other substances with a 
common mechanism of toxicity. EPA examined the available information on 
the cumulative effect of residues of plant-incorporated protectants 
derived through conventional breeding from sexually compatible plants 
as well as other substances in food that may have a common mechanism of 
toxicity with these residues. The Agency's consideration of the effects 
of the residues that are the subject of this exemption, and other 
substances that have a common mechanism of toxicity, in Unit IX.B.5. 
and Unit IX.B.6., included consideration of effects on infants and 
children.
    iv. Margin of safety. In determining whether the residues of plant-
incorporated protectants derived through conventional breeding from 
sexually compatible plants are safe, FFDCA section 408(b)(2)(C) directs 
EPA in the case of threshold effects to apply a tenfold margin of 
safety for the residues and other sources of exposure to infants and 
children to account for potential prenatal and postnatal toxicity and 
completeness of data effects with respect to exposure and toxicity to 
infants and children, unless a different margin will be safe (21 U.S.C. 
346a(b)(2)(C)). For residues of plant-incorporated protectants derived 
through conventional breeding from sexually compatible plants, EPA has 
determined that a tenfold margin of safety is not necessary to protect 
infants and children. EPA reaches this determination based on valid, 
complete and reliable information. EPA based its assessment of exposure 
and toxicity upon the information base described in Unit IX.A. and Unit 
IX.B.1. (Refs. 8, 11, 12, 13, 14, 15, 16, 17, 18, and 19) that arose 
through the long history of human consumption of food containing 
substances which are the subject of this exemption, and other animals 
that consume plants containing these substances, and other substances 
in food that may have a common mechanism of toxicity (Ref. 8). EPA also 
relied upon knowledge from the disciplines of plant genetics, plant 
physiology, phytopathology, microbial ecology, ecology, biochemistry 
(including the constituents of food) and plant breeding. Based on all 
of this information, EPA concludes that it is unlikely that consumption 
of food containing residues that are the subject of this exemption, 
including changes in exposure because of changes in the relative 
proportions of the different types of food consumed from infancy 
through childhood and into adulthood, would lead to any harm. Thus, EPA 
has concluded that consumption of food containing residues of plant-
incorporated protectants derived through conventional breeding from 
sexually compatible plants is safe for infants and children, and that a 
margin of safety need not be applied for these residues in food.
    11. Analytical methods. EPA has decided that there is no need to 
employ a practical method for detecting and measuring the levels of 
most of the substances in plants that might be used as plant-
incorporated protectants and thus might be residues of plant-
incorporated protectants derived through conventional breeding from 
sexually compatible plants. It is not anticipated that these substances 
would cause adverse effects. EPA has identified nine substances of 
plant origin that are found in plants that are part of the normal 
American diet and if present at high levels can present toxic effects. 
These are discussed in Unit IX.B.2. Practical methods exist for 
detecting and measuring the concentration of these substances in food 
(Ref. 22). EPA consulted with the Department of Health and Human 
Services (DHHS) in developing the proposed exemption and in issuing 
this final rule.

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

    Based on the information discussed in this document today and that 
discussed in the 1994 Federal Register documents and the supplemental 
documents and the associated record as described in Unit X., EPA 
concludes that there is a reasonable certainty that no harm will result 
to the United States population in general, and infants and children in 
the United States, from aggregate exposure to any residues of the 
pesticidal substance portion, or inert ingredients, of plant-
incorporated protectants derived through conventional breeding from 
plants sexually compatible with the recipient plant, including all 
anticipated dietary exposures and all other exposures for which there 
is reliable information. This finding is based on extensive use and 
experience, and the large associated literature on epidemiological 
studies, nutritional assessments with human volunteers and animal model 
testing of foods from plant varieties developed by moving traits among 
plants in sexually compatible populations. This information shows that 
adverse effects due to aggregate exposure through the dietary, non-food 
oral, dermal and inhalation routes are highly unlikely for pesticidal 
substances, or inert ingredients, derived through

[[Page 37852]]

conventional breeding from plants sexually compatible with the 
recipient plant. And in the unlikely event such adverse effects do 
occur, EPA has implemented mechanisms to ensure that it will be 
notified, and that FDA will be able to seize the adulterated food; 
i.e., the adverse effects reporting requirement at 40 CFR 174.71 and 
the condition limiting this exemption at Sec. 174.479.

X. Documents in the Official Record

    As indicated in Unit I.B.2., the official record for this rule has 
been established under docket control number OPP-300368B, the public 
version of which is available for inspection as specified in Unit 
I.B.2.

A. References

    The following books, articles and reports were used in preparing 
this final rule and were cited in this document by the number 
indicated:
    1. Whittaker, R. H. 1969. New concepts of kingdoms of organisms. 
Science, 163:150-160.
    2. Environmental Protection Agency. 2000. Summary of public 
comments and EPA responses on issues associated with plant-incorporated 
protectants (formerly plant-pesticides) for docket OPP-300368 and OPP-
300368A.
    3. Hanson, M., and J. Halloran. In a letter dated February 22, 1995 
on dockets OPP-300367 through OPP-300371.
    4. Goldburg, R. In a letter dated February 6, 1995 on dockets OPP-
300367 through OPP-300371.
    5. Rissler, J., and M. Mellon. In a letter dated January 23, 1995 
on dockets OPP-300367 through OPP-300371.
    6. Environmental Protection Agency. 1994. Joint meeting of the 
FIFRA 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.
    7. Raven, P. H., R. F. Evert, and S. E. Eichhorn. 1992. Biology of 
Plants. Fifth Edition. Worth Publishers, New York, New York.
    8. International Food Biotechnology Council. 1990. Biotechnologies 
and food; Assuring the safety of foods produced by genetic 
modification. In: Regulatory Toxicology and Pharmacology. Vol 12. 
Academic Press, New York, New York.
    9. Wilks, H. M., A. Cortes, D. C. Emery, D. J. Halsall, A. R. 
Clarke and J. J. Holbrook. 1992. Opportunities and limits in creating 
new enzymes. In: Enzyme Engineering XI. Edited by D. S. Clark and D. A. 
Estell. Annals of the New York Academy of Sciences. Vol. 672. The New 
York Academy of Sciences. New York, New York.
    10. Environmental Protection Agency. Meeting of the EPA 
Biotechnology Science Advisory Committee (BSAC); Subcommittee on plant-
pesticides. July 13, 1993. Final Report.
    11. World Cancer Research Fund and American Institute for Cancer 
Research. 1997. Food, Nutrition and the Prevention of Cancer: A Global 
Perspective. BANTA Book Group, Menasha, Wisconsin.
    12. Lampe, J. M. 1999. Health effects of vegetables and fruit: 
assessing mechanisms of action in human experimental studies. American 
Journal of Clinical Nutrition. Sep;70(3 Suppl):475S-490S.
    13. Ogomoto, I. A. Shibata and K. Fukuda. 2000. World Cancer 
ResearchFund/American Institute of Cancer Research 1997 recommendation: 
applicability to digestive tract cancer in Japan. Cancer Causes Control 
Jan;11(1):9-23.
    14. Joseph, J. A., B. Shukitt-Hale, N. A. Denisova, D. Bielinski, 
A. Martin, J. J. McEwen and P. C. Bickford. 1999. Reversals of age-
related declines in neuronal signal transduction, cognitive, and motor 
behavioral deficits with blueberry, spinach, or strawberry dietary 
supplementation.Journal of Neuroscience. Sep 15;19(18):8114-21.
    15. Segasothy, M. and P. A. Phillips. 1999. Vegetarian diet: 
panacea for modern lifestyle diseases? QJM Monthly Journal of the 
Association of Physicians. Sep;92(9):531-44.
    16. Joshipura, K. J., A. Ascherio, J. E. Manson, M. J. Stampfer, E. 
B. Rimm, F. E. Speizer, C. H. Hennekens, D. Spiegelman and W. C. 
Willett. 1999. Fruit and vegetable intake in relation to risk of 
ischemic stroke. Journal of the American Medical Association. 
Oct6;282(13)1233-9.
    17. Thompson, H. J., J. Heimendinger, A. Haegele, S. M. Sedlacek, 
C. Gillette, C. O'Neill, P. Wolfe and C. Conry. 1999. Effect of 
increased vegetable and fruit consumption on markers of oxidative 
cellular damage. Carcinogenesis. Dec;20(12):2261-6.
    18. New, S. A., S. P. Robins, M. K. Campbell, J. C. Martin, M. J. 
Garton, C. Boltin-Smith, D. A. Grubb, S. J. Lee and D. M. Reid. 2000. 
Dietary influences on bone mass and bone metabolism: further evidence 
of a positive link between fruit and vegetable consumption and bone 
health?American Journal of Clinical Nutrition. Jan;71(1):142-51.
    19. Michaud, D. S., D. Spiegelman, S. K. Clinton, E. B. Rimm, W. C. 
Willett and E. L. Giovannucci. 1999. Fruit and vegetable intake and 
incidence of bladder cancer in a male prospective cohort. Journal of 
the National Cancer Institute. Apr7;91(7):605-13.
    20. Environmental Protection Agency issue paper. 1994. FIFRA: 
Benefit and environmental risk considerations for inherent plant-
pesticides.
    21. Agrios, George. 1988. Plant Pathology. Third Edition. Academic 
Press. New York, New York.
    22. Environmental Protection Agency issue paper. 2000. Natural 
toxicants in food.
    23. USDA Agricultural Research Service Poisonous Plant Research 
Laboratory. Bulletin 415: Poisonous plants of the western United 
States: Neurotoxic and mycotoxic plants. [http://www.pprl.usu.edu/bulletin.htm]
    24. Hernando, J. E. and J. Leon (eds) Neglected Crops: 1492 from a 
different perspective. FAO Plant production and protection series No. 
26. Rome Italy, p. 131-148. 1994.
    25. Shibamoto, T. And L.F. Bjeldanes. 1993. Introduction to Food 
Toxicology. Academic Press, Inc. San Diego, New York, Boston.
    26. Ellenhorn, M. J. S. Schonwald, G. Ordog and J. Wasserberger. 
1997. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human 
Poisoning. Second Edition. Williams and Wilkins. Baltimore, MD
    27. Cooper, R. A., and H. F. Bunn. Hemolytic anemias. 1980. In: 
Harrison's Principles of Internal Medicine. Edited by. K. J. 
Isselbacher, R. D. Adams, E. Braunwald, R. G. Petersdorf and J. D. 
Wilson. McGraw-Hill Company.
    28. Coulston, F., and A. C. Kolbye. 1990. (Eds) Regulatory 
Toxicology and Pharmacology. 12(3), S20-S30.
    29. Concon, J. M. 1988. Food Toxicology: Principles and Concepts. 
Marcel Decker Inc. New York and Basel.
    30. Environmental Protection Agency issue paper. 2000. The 
glycoalkaloid class; solanine and chaconine: Mechanisms of action.
    31. D'Mello, J. P. F. 1997. Handbook of Plant and Fungal Toxicants. 
CBC Press. Boca Raton, New York.
    32. Tice, R. 1998. Chacoline and solanine: Review of the 
Toxicological Literature. Prepared for E. Zeiger, National Toxicology 
Program, National Institute of Environmental Health Sciences, National 
Institutes of Health. [http://ntp-server.niehs.nih.gov/htd. ...und/
ExecSumm/ChaconineSolanine.html
    33. Environmental Protection Agency. 2000. Benefits of fruits and 
vegetables.
    34. Taylor, P. 1996. Anticholinesterase agents. In: Goodman and 
Gilman's The Pharmacological Basis of Therapeutics. Ninth Edition. 
Edited by J. G. Hardman, L. E. Limbird,

[[Page 37853]]

P. B. Molinoff, and R. W. Rudden. McGraw-Hill Health Profession 
Division. New York, New York.
    35. Baker, D. C., R. F. Keeler, and W. P. Gaffield. 1988. Mechanism 
of death in syrian hamsters gavaged potato sprout material. Toxicologic 
Pathology. Vol. 16:333
    36. Environmental Protection Agency. 1999. Guidance for identifying 
pesticide chemicals and other substances that have a common mechanism 
of toxicity. FAX-on-Demand Number : (202) 401-0527. Item: 6055.
    37. Atlas, R. and R. Bartha. 1987. Microbial Ecology. Benjamin/
Cummings Publishing Company, Inc. Menlo Park, California.
    38. National Research Council. 1999. Hormonally Active Agents in 
the Environment. National Academy Press. Washington DC.
    39. Yunginger, J. W. 1991. Food Antigens. In: Food Allergy: Adverse 
Reactions to Foods and Food Additives. Edited by D. D. Metcalfe, H. A. 
Sampson, and R. A. Simon. Blackwell Scientific Publications. Cambridge, 
Massachusetts.
    40. O'Mahony, S. And A. Ferguson. 1991. Gluten-Sensitive 
Enteropathy (Celiac Disease). In: Food Allergy: Adverse Reactions to 
Foods and Food Additives. Edited by D. D. Metcalfe, H. A. Sampson, and 
R. A. Simon. Blackwell Scientific Publications. Cambridge, 
Massachusetts.
    41. Environmental Protection Agency issue paper. 2000. Dermal and 
inhalation exposure to plant substances.
    42. Lovell, C. R. 1993. Plants and the skin. First edition. Oxford, 
Blackwell Scientific Publications.
    43. Guy, R. H., and J. Hadgraft. 1991. Principles of skin 
permeability relevant to chemical exposure. In: Dermal and Ocular 
Toxicology: Fundamentals and Methods. Edited by D. W. Hobson. CRC Press 
Boca Raton, Florida.
    44. Murray, M. T. 1995. The Healing Power of Herbs. Prima 
Publishing, Rocklin, California.
    45. Glinsukon, T., Stitmunnaithum, V., Toskulkao, C., Buranawuti, 
T., and V. Tangkrisanavinont. Acute toxicity of capsaicin in several 
animal species. Toxicon. 18(2):215-20. 1980.
    46. Environmental Protection Agency. 1997. Exposure Factors 
Handbook. Volume 1. National Center for Environmental Assessment. EPA/
600/P-95/002Fa.
    47. Environmental Protection Agency. 2000. Economic analysis of the 
plant-incorporated protectant regulations under the Federal 
Insecticide, Fungicide, and Rodenticide Act.

B. Additional Information

    The complete official record for this rulemaking includes:
    The docket identified by the docket control number OPP-300370 for 
the document entitled ``Proposed Policy: Plant-Pesticides Subject to 
the Federal Insecticide, Fungicide, and Rodenticide Act and the Federal 
Food, Drug, and Cosmetic Act'' (59 FR 60496, November 23, 1994) (FRL-
4755-2).
    The docket identified by the docket control number OPP-300369 for 
the document entitled ``Plant-Pesticides Subject to the Federal 
Insecticide, Fungicide and Rodenticide Act; Proposed Rule'' (59 FR 
60519, November 23, 1994) (FRL-4755-3).
    The docket identified by the docket control number OPP-300368 for 
the document entitled ``Plant-Pesticides; Proposed Exemption From the 
Requirement of a Tolerance Under the Federal Food, Drug, and Cosmetic 
Act'' (59 FR 60535, November 23, 1994) (FRL-4758-8).
    The docket identified by the docket control number OPP-300371 for 
the document entitled ``Plant-Pesticides; Proposed Exemption From the 
Requirement of a Tolerance Under the Federal Food, Drug, and Cosmetic 
Act for Nucleic Acids Produced in Plants'' (59 FR 60542, November 23, 
1994) (FRL-4755-5).
    The docket identified by the docket control number OPP-300367 for 
the document entitled ``Plant-Pesticides; Proposed Exemption From the 
Requirement of a Tolerance Under the Federal Food, Drug, and Cosmetic 
Act for Viral Coat Proteins Produced in Plants'' (59 FR 60545, November 
23, 1994) (FRL-4755-4).
    The docket identified by the docket control number OPP-300370A for 
the document entitled ``Plant-Pesticide Subject to the Federal 
Insecticide, Fungicide, and Rodenticide Act and the Federal Food, Drug, 
and Cosmetic Act; Reopening of Comment Period'' (61 FR 37891, July 22, 
1996) (FRL-5387-4).
    The docket identified by the docket control number OPP-300368A for 
the document entitled ``Plant-Pesticides; Supplemental Notice of 
Proposed Rulemaking'' (62 FR 27132, May 16, 1997) (FRL-5717-2).
    The docket identified by the docket control number OPP-300371A for 
the document entitled ``Plant-Pesticides; Nucleic Acids; Supplemental 
Notice of Proposed Rulemaking'' (62 FR 27142, May 16, 1997) (FRL-5716-
7).
    The docket identified by the docket control number OPP-300367A for 
the document entitled ``Plant-Pesticides; Viral Coat Proteins; 
Supplemental Notice of Proposed Rulemaking'' (62 FR 27149, May 16, 
1997) (FRL-5716-6).
    The docket identified by the docket control number OPP-30069A for 
the document entitled ``Plant-Pesticides, Supplemental Notice of 
Availability of Information'' (64 FR 19958, April 23, 1999) (FRL-6077-
6).
    The docket identified by the docket control number OPP-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-300368B for 
this document (FRL-6057-6).
    Also include in the complete official public record are:
    1. Public comments submitted in response to the proposals and 
supplemental documents cited in this Unit X.B.
    2. Reports of all meetings of the Biotechnology Science Advisory 
Committee and the FIFRA Science Advisory Panel pertaining to the 
development of this final rule.
    3. The Economic Analysis (EA) for the final rule on FIFRA 
regulations for plant-incorporated protectants, and documents 
supporting the EA (Ref. 47).
    4. Support documents and reports.
    5. Records of all communications between EPA personnel and persons 
outside EPA pertaining to the final rule. (This does not include any 
inter-agency and intra-agency memoranda, unless specifically noted in 
the Indices of the dockets).
    6. Published literature that is cited in this document.
    7. The response to comments document pertaining to the development 
of this final rule (Ref. 2).

XI. Regulatory Assessment Requirements

    This final rule establishes an exemption from the tolerance 
requirement under FFDCA section 408 and does not impose any other 
regulatory requirements. As such, The Office of Management and Budget 
(OMB) has exempted these types of actions from review under Executive

[[Page 37854]]

Order 12866, entitled Regulatory Planning and Review (58 FR 51735, 
October 4, 1993).
    This action does not contain any information collections subject to 
OMB approval under the Paperwork Reduction Act (PRA), 44 U.S.C. 3501 et 
seq., nor does it require OMB review or any Agency action under 
Executive Order 13045, entitled Protection of Children from 
Environmental Health Risks and Safety Risks (62 FR 19885, April 23, 
1997).
    This action does not require any special considerations under 
Executive Order 12898, entitled Federal Actions to Address 
Environmental Justice in Minority Populations and Low-Income 
Populations (59 FR 7629, February 16, 1994), nor does it involve any 
technical standards that would require Agency consideration of 
voluntary consensus standards pursuant to section 12(d) of the National 
Technology Transfer and Advancement Act of 1995 (NTTAA), Public Law 
104-113, section 12(d) (15 U.S.C. 272 note).
    This action does not impose any enforceable duty or contain any 
unfunded mandate, and will not otherwise significantly or uniquely 
affect small governments as described under Title II of the Unfunded 
Mandates Reform Act of 1995 (UMRA) (Public Law 104-4). This rule does 
not significantly or uniquely affect the communities of Indian trial 
governments, nor does it involve or impose any requirements that affect 
Indian Tribes. Accordingly, the requirements of section 3(b) of 
Executive Order 13084, entitled Consultation and Coordination with 
Indian Tribal Governments (63 FR 27655, May 19, 1998), do not apply to 
this rule. Executive Order 13175, entitled Consultation and 
Coordination with Indian Tribal Governments (65 FR 67249, November 6, 
2000), which took effect on January 6, 2001, revokes Executive Order 
13084 as of that date. EPA developed this rulemaking, however, during 
the period when Executive Order 13084 was in effect; thus, EPA 
addressed tribal considerations under Executive Order 13084. For the 
same reasons stated for Executive Order 13084, the requirements of 
Executive Order 13175 do not apply to this rule either. For the same 
reasons, this rule does not have any substantial direct effect on 
States, on the relationship between the national government and the 
States, or on the distribution of power and responsibilities among the 
various levels of government, as specified in Executive Order 13132, 
entitled Federalism (64 FR 43255, August 10, 1999). This rule directly 
regulates growers, food processors, food handlers and food retailers, 
not States. This action does not alter the relationships or 
distribution of power and responsibilities established by Congress in 
the preemption provisions of FFDCA section 408(n)(4).
    Pursuant to section 605(b) of the Regulatory Flexibility Act (RFA) 
(5 U.S.C. 601 et seq.), the Agency hereby certifies that this final 
rule will not have a significant economic impact on a substantial 
number of small entities. The Agency's determination is based on the 
fact that an exemption from the requirement of a tolerance under FFDCA 
section 408, such as that contained in this rule, will not adversely 
affect any small businesses. Additional information about the Agency's 
determination may be found in the small entity impact analysis prepared 
as part of the economic analysis for the FIFRA rulemaking, which is 
available in the public version of the official record under OPP-
300368B (Ref. 47). The Agency has also previously assessed whether 
establishing tolerances, exemptions from tolerances, raising tolerance 
levels or expanding exemptions might adversely impact small entities 
and concluded, as a general matter, that there is no adverse economic 
impact associated with these actions. See 46 FR 24950, May 4, 1981.
    This rule is not subject to Executive Order 13211, entitled Actions 
Concerning Regulations That Significantly Affect Energy Supply, 
Distribution, or Use (66 FR 28355, May 22, 2001), because this action 
is not expected to affect energy supply, distribution, or use.

XII. Submission to Congress and the Comptroller General

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

List of Subjects in 40 CFR Part 174

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


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

    Therefore, 40 CFR chapter I is amended as follows:

PART 174--[AMENDED]

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

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


    2. Section 174.479 is added to subpart W to read as follows:


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 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 from a plant 
that is sexually compatible with the recipient food plant.
    (b) The genetic material has never been derived from a source that 
is not sexually compatible with the recipient food plant.
    (c) The residues of the pesticidal substance are not present in 
food from the plant at levels that are injurious or deleterious to 
human health.

[FR Doc. 01-17983 Filed 7-16-01; 11:42 am]
BILLING CODE 6560-50-S