[Federal Register Volume 59, Number 225 (Wednesday, November 23, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-28823]


[[Page Unknown]]

[Federal Register: November 23, 1994]


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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180

[OPP-300368; FRL-4758-8]
RIN 2070-AC02

 

Plant-Pesticides; Proposed Exemption From the Requirement of a 
Tolerance Under the Federal Food, Drug, and Cosmetic Act

AGENCY: Environmental Protection Agency (EPA).

ACTION: Proposed rule.

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SUMMARY: This document proposes an exemption from the requirement of a 
tolerance under the Federal Food, Drug, and Cosmetic Act (FFDCA) for 
specific categories of pesticidal substances produced by plants to 
protect them against pests and disease. Pesticidal substances produced 
by plants, along with the genetic material necessary for the production 
of these substances, have been designated ``plant-pesticides'' by the 
Agency. The categories of plant-pesticides EPA is proposing to exempt 
from the requirement of a tolerance are based upon evaluation of the 
potential for new dietary exposures to these pesticidal substances when 
they are produced in plants or plant parts used as raw agricultural 
commodities. EPA believes that a tolerance for these categories of 
plant-pesticides is not necessary to protect the public health.

DATES: Comments identified by the docket control number [OPP-300368] 
must be received on or before January 23, 1995.

ADDRESSES: Submit written comments by mail to: Program Resources 
Section, Public Response and Program Resources Branch, Field Operations 
Division (7506C), Environmental Protection Agency, 401 M St., SW., 
Washington, DC 20460. In person, bring comments to Rm. 1132, Crystal 
Mall #2, 1921 Jefferson Davis Highway, Arlington, VA 22202.
    Information submitted as a comment concerning this document may be 
claimed confidential by marking any part or all of that information as 
``Confidential Business Information'' (CBI). Information so marked will 
not be disclosed except in accordance with procedures set forth in 40 
CFR part 2. A copy of the comment that does not contain CBI must be 
submitted for inclusion in the public record. Information not marked 
confidential may be disclosed publicly by EPA without prior notice. All 
written comments will be available for public inspection in Rm. 1132 at 
the Virginia address given above from 8 a.m. to 4 p.m., Monday through 
Friday, excluding legal holidays.

FOR FURTHER INFORMATION CONTACT: By mail: Bernice Slutsky, Science and 
Policy Staff, Office of Prevention, Pesticides and Toxic Substances 
(7101), Environmental Protection Agency, 401 M St., SW., Washington, DC 
20460, Telephone number: 202-260-6900.

SUPPLEMENTARY INFORMATION:

I. Introduction

    Substances that are produced in plants to enable the plants to 
resist pests or disease are pesticides under section 2 of the Federal 
Insecticide, Fungicide, and Rodenticide Act (FIFRA) (i.e., if they are 
. . .``intended for preventing, destroying, repelling, or mitigating 
any pest'') regardless of whether the pesticidal capabilities evolved 
in the plants or were introduced by breeding or through the techniques 
of modern biotechnology. These substances, along with the genetic 
material necessary to produce the substances, are designated by the 
Agency as ``plant-pesticides.''
    There are a number of types of substances that are produced in 
plants to protect them against pest attack and disease. For example, 
phytoalexins (plant-produced substances that act against microbial 
phytopathogens) could be considered plant-pesticides because of their 
role in plant resistance to plant pests. These substances are examples 
of plant-pesticides that can be introduced into a plant through 
traditional breeding. Another example of a plant-pesticide is an 
insecticidal delta endotoxin from the bacterium, Bacillus 
thuringiensis, introduced into plants through biotechnology techniques 
to impart or enhance resistance to insect pests.
    In the past, EPA has addressed, under FFDCA, how it regulates 
substances that are extracted from plants and used as pesticides on 
food or feed. For example, a tolerance has been set for pyrethrum that 
is extracted from plants and applied to food or feed. However, until 
now, the Agency has not clearly explained how it intends to regulate 
pesticidal substances produced in plants and not extracted from the 
plant (``plant-pesticides'') under FFDCA. For example, if a food plant 
could be modified, for pesticidal purposes, to produce pyrethrum, EPA 
has not explained how this pyrethrum would be regulated under FFDCA.
    The Agency is proposing to exempt certain categories of plant-
pesticides that the Agency believes would not result in new dietary 
exposures (e.g., not significantly different from what humans are 
currently exposed to in the food supply) and therefore do not require 
the establishment of a tolerance to protect the public health. There 
are circumstances where EPA believes that plant-pesticides should be 
regulated by EPA for the purpose of either setting a tolerance or 
issuing a specific exemption from the requirement of a tolerance for a 
particular plant-pesticide. In general, plant-pesticides that would 
result in significantly new or different dietary exposures would be 
subject to EPA review under FFDCA tolerance procedures. These 
categories of plant-pesticides would not be exempt from the requirement 
of a tolerance under this proposal.
    This proposed rule, is one of several documents published in 
today's Federal Register that address EPA's regulation of plant-
pesticides. The other notices are: (1) A proposed policy statement that 
generally describes how EPA proposes to regulate plant-pesticides under 
the FIFRA and FFDCA (``Plant-pesticides subject to the Federal 
Insecticide, Fungicide, and Rodenticide Act and the Federal Food, Drug, 
and Cosmetic Act; Proposed Policy''); (2) a proposed regulatory 
amendment that would describe categories of plant-pesticides that are 
subject to or exempt from regulation under FIFRA and clarifies the 
status of plants that produce plant-pesticides (``Plant-pesticides 
Subject to the Federal Insecticide, Fungicide, and Rodenticide Act; 
Proposed Rule''); (3) a proposed exemption from the requirement of a 
tolerance under FFDCA for viral coat proteins (``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''); and (4) a proposed exemption from the requirement of a 
tolerance under FFDCA for nucleic acids, including deoxyribonucleic and 
ribonucleic acids (``Plant-pesticides; Proposed Exemption from the 
Requirement of a Tolerance Under the Federal Food, Drug, and Cosmetic 
Act for Nucleic Acids Produced in Plants''). A plant-pesticide would be 
defined as a pesticidal substance that is produced in a living plant 
and the genetic material necessary for the production of the substance, 
where the substance is intended for use in the living plant. The 
definition of the active ingredient for plant-pesticide would be the 
same as the definition for plant-pesticide (see Federal Register 
document entitled, ``Plant-pesticides Subject to the Federal 
Insecticide, Fungicide, and Rodenticide Act; Proposed Rule'').
    This proposal addresses only the component of plant-pesticides 
comprising the pesticidal substance produced in food plants. The 
component comprising the genetic material necessary for the production 
of these substances is addressed in another proposed exemption from the 
requirement of a tolerance for nucleic acids produced in plants as part 
of a plant-pesticide (see the Federal Register 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'').

II. Statutory Authority

    This exemption from the requirement of tolerance is being proposed 
under the authority of section 408(c) of the Federal Food, Drug, and 
Cosmetic Act (21 U.S.C. 321 et. seq.). The reorganization plan of 1970 
reallocated the authority under FFDCA to regulate pesticide residues in 
foods and animal feeds to EPA. Under FFDCA section 408, pesticide 
chemicals added to a raw agricultural commodity, that are not 
``generally recognized as safe'' (GRAS), are deemed to be unsafe unless 
a tolerance, or an exemption from the requirement of a tolerance, for 
such pesticide residues is established and the pesticide residue is 
within the tolerance limits. Section 408 of the FFDCA applies to all 
``pesticide chemicals'' which are defined in section 201(q) of the 
FFDCA as:

    any substance which, alone, in chemical combination or in 
formulation with one or more other substance, is ``a pesticide'' 
within the meaning of [FIFRA] . . .and which is used in the 
production, storage, or transportation of raw agricultural 
commodities.

    Under FFDCA section 408(c), EPA can exempt, by regulation, any 
pesticidal chemical from the necessity of a tolerance when such 
tolerance is not necessary to protect the public health. The result of 
such an exemption is also to authorize residues of the pesticidal 
chemical in any processed foods made from the raw agricultural 
commodity that contain the residue as a result of the pesticide on the 
raw agricultural commodity.

III. Proposed Exemptions

    In developing this proposal, EPA identified three categories of 
plant-pesticides that can be produced in recipient food plants where 
the recipient food plant would be defined as the plant into which the 
plant-pesticide is introduced and in which the plant-pesticide is 
produced. The three categories of plant-pesticides are: (1) Plant-
pesticides that are derived from food or non-food plants that are 
closely related to the recipient plant; (2) plant-pesticides that are 
derived from food plants that are not closely related to the recipient 
food plant and that would not result in significantly different dietary 
exposures when produced in the recipient food plant; and (3) plant-
pesticides either derived from nonfood plants that are not closely 
related to the recipient plant or derived from a nonplant source. EPA 
is proposing to exempt from the requirement of a tolerance plant-
pesticides in categories (1) and (2) above and these are defined in the 
proposed regulatory text. In the preamble of this document, these two 
categories are described in Units III.A. and III.B., respectively and 
analyzed in Unit III.D. Plant-pesticides in category (3) above would 
not be exempt from the requirement of a tolerance under this proposal.

A. Category 1: Exemption of Plant-pesticides Derived from Closely 
Related Plants

    This exemption is based upon the premise 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.
    For the purposes of describing this category of plant-pesticides, 
EPA is presenting three options for a standard based on the relatedness 
of plants. These options are described in Unit III.A. with the analysis 
of the options in Unit III.D. of this preamble. The Agency's aim when 
it selects one of these approaches for its final rule is to: (1) 
Distinguish, on a risk basis, those plant-pesticides that would result 
in new dietary exposures from those that would not; (2) provide a 
standard of sufficient regulatory clarity so that the public, industry, 
and the Agency can easily identify those plant-pesticides that would be 
subject to regulation; and (3) create as similar a scope of regulation 
as possible under FFDCA and FIFRA given the differences in mandate and 
structure of the two statutes. (See ``Plant-pesticides Subject to the 
Federal Insecticide, Fungicide, and Rodenticide Act; Proposed Rule'' 
for details on the scope options proposed under FIFRA.) Note, that some 
options offered in the proposed rule under FIFRA are not offered in 
this proposed regulation under FFDCA because EPA believes that they 
would not be appropriate for describing a category of plant-pesticides 
that would not present new dietary exposures. The options that are not 
discussed under FFDCA are not EPA's preferred option under FIFRA.
    1. Option 1: Plant-pesticides derived from sexually compatible 
plants. The preferred approach EPA is proposing to use, in establishing 
this exemption, is based on the concept of sexual compatibility as a 
measure of relatedness between plants. The use of the standard of 
sexual compatibility is embodied in the following language from the 
proposed regulatory text:

    Residues of pesticidal substances produced in living plants as 
plant-pesticides are exempt from the requirement of a tolerance if 
the genetic material that encodes for a pesticidal substance or 
leads to the production of a pesticidal substance is derived from 
plants that are sexually compatible with the recipient plant and has 
never been derived from a source that is not sexually compatible 
with the recipient plant;. . . .
    2. Option 2: Plant-pesticides derived from plants within the same 
genus or from sexually compatible plants. The standard under this 
option would rely primarily on the taxonomic grouping of genus and 
would exempt from the requirement of a tolerance plant-pesticides that 
are moved between source and recipient plants that are in the same 
genus. The assumption underlying this approach is that this grouping 
correlates to a relatively high degree of relatedness even though not 
all plants in a genus are sexually compatible. For example, traits 
ranging from flower morphology to the presence of particular alkaloids 
and flavonoids have been used to determine whether to classify a plant 
species in a particular genus. Recognizing that some plants that are 
sexually compatible are classified in different genera and assuming 
that sexual compatibility correlates with a high degree of relatedness, 
EPA also includes a provision extending the exemption to include 
sexually compatible plants from any genera. The language defining this 
option would be as follows. [Residues of pesticidal substances produced 
in living plants as plant-pesticides are exempt from the requirement of 
a tolerance if:]

    The genetic material that encodes for a pesticidal substance or 
leads to the production of a pesticidal substance:
    (1) Is derived from plants that are within the same genus as the 
recipient plant [regardless of sexual compatibility] or, is derived 
from plants that are sexually compatible with the recipient plant; 
and
    (2) Has never been derived from a source outside the same genus 
that is not sexually compatible with the recipient plant.

B. Category 2: Plant-pesticides Derived from Food Plants that are Not 
Closely Related to the Recipient Plant

    There are circumstances where experience with exposure can be 
inferred for plant-pesticides introduced into food plants from other 
food plants that are not closely related to the recipient plant. For 
plant-pesticides derived from a food plant that is not closely related 
to the recipient food plant, there is experience with exposure because 
both plants have contributed to the food supply. Thus, the Agency is 
proposing to exempt from the requirement of a tolerance plant-
pesticides derived from food plants that are not closely related to the 
recipient plant, if there would not be significantly different dietary 
exposures when the plant-pesticide is produced in the recipient food 
plant. The criteria defining this exemption are as follows:

    Residues of pesticidal substances produced in living plants as 
plant-pesticides are exempt from the requirement of a tolerance when 
the genetic material that encodes for a pesticidal substance or 
leads to the production of a pesticidal substance is derived from 
plants that are not sexually compatible with the recipient plant if:
    (1) The genetic material that encodes for a pesticidal substance 
or leads to the production of a pesticidal substance is derived from 
food plants; and
    (2) The pesticidal substance would not result in significantly 
different dietary exposures.

C. Terms Used

    The following are terms used in the two options for the Category 1 
exemption presented in Unit III.A. and the Category 2 exemption 
presented in Unit III.B. of this preamble.
    The phrase ``the genetic material that encodes for a pesticidal 
substance or leads to the production of a pesticidal substance'' refers 
to genetic material that directly encodes for the production of a 
pesticidal substance or encodes for enzymes that lead to the production 
of a pesticidal substance (e.g., phenylalanine ammonia-lyase (PAL) 
catalyzes the first reaction in the synthesis of such phytoalexins as 
pterocarpans in Leguminosae and furanocoumarins in Solanaceae and 
Umbelliferae; Ref. 2). For the purposes of this exemption under FFDCA, 
this phrase is not intended to include regulatory regions or noncoding, 
nonexpressed nucleotide sequences when the gene would otherwise be 
exempt. For the exemptions proposed in this document, these regulatory 
regions and noncoding, nonexpressed nucleotide sequences may be derived 
from any source. For example, if a viral promoter attached to a corn 
gene encoding a pesticidal substance is introduced into another corn 
variety, the gene and the viral promotor genetic construct would meet 
the criteria of these exemptions.
    The definition for ``sexually compatible'' would mean being capable 
of forming a viable zygote through the fusion of two gametes and can 
include the use of bridging crosses and the use of wide cross breeding 
techniques of surgical alteration of the plant pistol, bud pollination, 
mentor pollen, immunosuppressants, in vitro fertilization, pre- and 
post- pollination hormone treatments, manipulation of chromosome 
numbers, and embryo culture. Wide crosses, for the purpose of this 
exemption, also include ovary and ovule cultures. EPA believes that the 
production of viable zygotes through these techniques indicates a 
sufficient level of relatedness between the parental plants involved to 
be included under the rubric of ``sexually compatible.''
    The phrase, ``. . .result in significantly different dietary 
exposure. . .'' relates only to the Category 2 exemption and would 
mean:

    (1) The pesticidal substance is produced in inedible portions of 
the source food plant, but, in the recipient plant, the pesticidal 
substance is present in the plant's edible portions;
    (2) The pesticidal substance is produced in the immature, but 
not in the mature, edible portions of the source food plant, but, in 
the recipient plant, the pesticidal substance is present in the 
mature, edible portions;
    (3) The pesticidal substance is from a source food plant 
normally cooked or processed prior to consumption and is produced in 
a recipient plant that is not normally cooked or processed prior to 
consumption;
    (4) The pesticidal substance is derived from a source food plant 
that is not a major crop for dietary consumption and is introduced 
into a recipient plant that is a major crop for dietary consumption.

    The ``source food plant'' is the donor of the genetic material that 
encodes for a pesticidal substance or leads to the production of a 
pesticidal substance.
    The phrase ``. . .has never been derived from a source plant that 
is not sexually compatible to the recipient plant. . .'' (Category 1) 
is meant to indicate in the proposed regulatory text that the plant-
pesticide would not qualify for the exemption in this proposal if the 
genetic material, for example, is introduced into a plant from a 
sexually incompatible source and subsequently introduced into other, 
sexually compatible plants. An example of such a situation would be if 
the Bacillus thuringiensis delta endotoxin is introduced into wheat and 
the endotoxin producing wheat plants subsequently hybridized using wide 
cross techniques with rye to produce triticale. The endotoxin produced 
in the triticale would not be eligible for the exemption.

D. Analysis of Exemptions

    This unit contains analysis of the two options presented in Unit 
III.A., the exemption presented in Unit III.B., and the relationship 
between the options in Unit III.A. and the exemption in Unit III.B. of 
this preamble.
    1. Analysis of options for category 1 exemption presented in Unit 
III.A. Under FFDCA, the options must be examined specifically within 
the context of the food supply and dietary consumption. Many substances 
having pesticidal activity occur naturally at low concentrations in the 
edible parts of plants and have long been accepted as part of the human 
diet. Extensive use and experience show the safety of foods containing 
these substances. For many foods, the naturally occurring toxicants 
they may contain, including pesticidal substances, are known (Ref. 1). 
Also, the established practices that plant breeders employ in selecting 
and developing new plant varieties, such as chemical analyses, taste-
testing, and visual analyses, have historically proven to be reliable 
for ensuring food safety. That there are few examples of new plant 
varieties causing food safety concerns, despite the large numbers of 
new varieties introduced into commerce each year, is a reflection of 
the effectiveness of this process.
    Sexually compatible plants are more apt to share traits than are 
unrelated plants. It is a common expectation that similarity is 
associated with the degree of relatedness. Natural hybridization and 
selection have produced groups of plants which have a common gene pool. 
Generations of artificial hybridization practiced to produce improved 
crops for cultivation have tended to increase the extent of relatedness 
among elements of a broader segment of agricultural plants.
    The practice of saving seed from desirable plants has been going on 
for thousands of years, and using controlled crosses to produce plant 
hybrids has been documented since the eighteenth century. Since the 
rediscovery of Mendel's work on the inheritance of traits, there is a 
base of experience of 50 to 100 years of breeding for most major crops. 
During that time, it has been common agricultural practice to cross 
sexually compatible wild relatives with crop plants to develop crop 
varieties with better pest resistance. Sexually compatible crop 
varieties are also crossed with each other to achieve better pest 
resistance in their progeny.
    EPA believes, based on this experience, that most plant varieties 
developed by plant breeders using genetic material from plants that 
meet the sexually compatible standard produce food that is safe for 
human consumption and/or that appropriate processing procedures are 
widely known and routinely used by consumers in preparation of food 
from such sources.
    A plant-pesticide would meet the criteria of this standard if the 
plants that are used as genetic donors are not themselves food plants, 
as long as they are sexually compatible with the recipient food plant 
that is producing the plant-pesticide. It has been common agricultural 
practice to introduce traits from sexually compatible wild relatives 
into plant varieties to be used as food plants. These wild, sexually 
compatible relatives of cultivated plants do not have any history of 
human consumption but have safely contributed traits through sexual 
recombination to cultivars on the market. Food plant varieties 
developed in this way have been introduced and consumed by humans for 
many years with no observed adverse affects. For example, under this 
standard, a wild species related to tomato may be used as a source of 
genetic material in developing a cultivated tomato variety.
    EPA proposes to extend the concept of sexual compatibility to 
include wide crosses because wide crosses are commonly used to expand 
the gene pool for varietal improvement, and EPA believes that the use 
of wide crosses to produce a viable zygote indicates a fairly high 
degree of relatedness and thus a high probability that the parental 
plants have common constitutions. However, for regulatory purposes it 
is somewhat difficult to define what constitutes a wide cross since 
techniques may change over time. EPA is thus proposing to define, for 
the purposes of this rulemaking, wide crosses based on existing 
techniques, with a provision to add to the definition as the 
Administrator determines is appropriate.
    As described in Unit III.A. of this preamble, EPA is considering a 
second option for describing relatedness based primarily on the 
taxonomic standard of genus rather than on sexual compatibility alone. 
Under this approach, a plant-pesticide would be exempt if the genetic 
material encoding for a pesticidal substance or leading to the 
production of a pesticidal substance is derived from a plant within the 
same genus as the recipient plant. EPA recognizes that some plants that 
are closely related (as evidenced by sexual compatibility) are not 
classified in the same genus. Under this second option, EPA would 
extend the exemption to plant-pesticides derived from plants sexually 
compatible with the recipient plant, as well as to intrageneric plant-
pesticides.
    Plant species within the same genus may have become separated by 
geography, timing of pollination, or other factors to form two distinct 
populations no longer sexually compatible. Events such as mutation and 
environmental selection most likely occurred and reinforced the 
isolation and uniqueness of the gene pools. However, the ability to 
overcome these incompatibility barriers between species in the same 
genera through human intervention (e.g., wide crosses) is evidence that 
such plants are fairly closely related and share a common constitution. 
The majority of successful wide crosses and bridging crosses to date 
have occurred between species within the same genus.
    However, taxonomy of plant genera may be an artificial standard 
within the context of the food supply since there may be species within 
any given genus that are not used as food or may not have contributed 
traits to food through breeding and thus experience with their risks 
may not exist. In addition, the experience base (e.g., experience with 
whether or not naturally occurring toxicants are present) for most of 
the species within most genera is more limited than for those species 
comprising the major food crops.
    Under Option 1, a plant-pesticide produced from genetic material 
derived from a plant in the same genus as, but not sexually compatible 
with, the recipient plant would not qualify for the exemption. In 
contrast, under Option 2, this plant-pesticide would qualify for the 
exemption. It is, therefore, possible under Option 2 for a plant-
pesticide to be exempt from the requirement of a tolerance without the 
base of experience that breeders have for sexually compatible plants.
    Finally, none of the options are intended to exempt plant-
pesticides which are significantly different in structure or function 
from the plant-pesticide as it occurs in the source plant. Such 
significantly modified plant-pesticides would no longer be considered 
by the Agency to be ``derived from the source plant.'' Rearrangements 
or modifications of the sequence encoding a plant-pesticide, for 
example, could result in plant-pesticides with significantly different 
structures and/or functions from that in the source plant and these 
would not be exempt. If this type of modification were to occur, the 
base of experience for that plant-pesticide in food would no longer be 
relevant.
    2. Analysis of Category 2 exemption presented in Unit III.B. Based 
on the experience with food plants, conclusions as to dietary safety of 
these foods can be drawn. EPA has concluded that an exemption from the 
requirement of a tolerance is appropriate for certain pesticidal 
substances produced from genetic material derived from food plants that 
are not close relatives to the recipient plant producing the plant-
pesticide if there will not be significantly different human dietary 
exposures. The Agency has defined a set of criteria to determine 
whether significantly different dietary exposures from the these plant-
pesticides would occur. For example, if a pesticidal substance is 
normally only produced in inedible portions or immature fruit of the 
food plant, the Agency would require a tolerance review if the modified 
food plant were to produce that substance in its mature fruit or edible 
portions. For example, tomatine is a toxicant produced in much higher 
amounts in immature tomato fruit (that is normally not eaten) than it 
is in the mature fruit. If the genetic material leading to the 
production of tomatine were introduced into a plant for pesticidal 
purposes such that the tomatine were produced in the mature fruit as it 
is in the immature fruit, EPA would need to conduct a tolerance review 
to determine whether a tolerance is necessary to protect the public 
health. Similarly, if a pesticidal substance is produced in a food that 
is almost always cooked or processed prior to consumption, the Agency 
would want to conduct a tolerance review if another food plant that is 
not cooked or processed prior to consumption is modified to produce the 
substance. For example, some beans are rich in lectins, glycoproteins 
that are natural toxicants. Soaking and cooking the beans destroys the 
lectin. If the genetic material encoding for the lectin were 
transferred, for pesticidal purposes, from beans to a plant which is 
not normally cooked (e.g., lettuce), EPA would need to conduct a 
tolerance review. A significantly different dietary exposure could also 
result if a widely consumed food staple such as corn is modified to 
produce a pesticidal substance from a food crop with minor consumption 
such as eggplant.
    EPA is also considering adding another criterion to the exemption 
from the requirement of a tolerance for categories of plant-pesticides 
that would not result in significantly different dietary exposures (see 
Unit III.B. of this preamble). This criterion would address the 
potential for allergenicity of plant-pesticides in food. Under this 
criterion, if a plant-pesticide is derived from a commonly allergenic 
food, the plant-pesticide would not be exempt from tolerance 
requirements and the Agency would conduct a tolerance review on a case-
by-case basis to determine whether to establish an exemption from the 
requirement of a tolerance, establish a tolerance, or deny a tolerance. 
Some examples of foods that commonly cause an allergenic response are 
milk, eggs, fish, crustacea, molluscs, tree nuts, wheat, and legumes 
(particularly peanuts and soybeans).
    3. Analysis of the relationship between the options for the 
Category 1 exemption in Unit III.A and the Category 2 exemption in Unit 
III.B. Option 2 discussed in Unit III.A. of this preamble has different 
implications for the exemption described in Unit III.B. of this 
preamble than does Option 1 in Unit III.A. If the concept in the Unit 
III.B. exemption were transcribed to fit with Option 2, a distinction 
would be drawn between plant-pesticides derived from food plants in the 
same genus as the recipient plant but not sexually compatible with the 
recipient plant, and plant-pesticides derived from food plants outside 
the same genus as the recipient plants and also not sexually compatible 
with the recipient plant. This distinction may be somewhat artificial 
under FFDCA since it is based on a taxonomic standard rather than one 
of experience with dietary exposure. The Unit III.B. exemption would 
read as follows if it were coupled with Option 2:

    Residues of pesticidal substances produced in plants that are 
not in the same genus as the recipient plants are exempt from the 
requirement of a tolerance if:
    (1) the genetic material that encodes for a pesticidal substance 
or leads to the production of a pesticidal substance is derived from 
food plants and
    (2) the pesticidal substances would not result in significantly 
different dietary exposures.
    ``Significantly different dietary exposures'' would be defined as 
in Unit III.C. of this preamble.
    Modifying the exemption in Unit III.B. in such a way raises the 
following specific question. Should EPA treat plant-pesticides derived 
from sexually incompatible food plants outside the genus of the 
recipient plant differently from plant-pesticides derived from sexually 
incompatible food plants within that genus? In the first case, the 
plant-pesticide (produced from genetic material derived from sexually 
incompatible food plants outside the genus of the recipient plant) 
would have to meet certain criteria to qualify for an exemption. In the 
latter case, the plant-pesticide (produced from genetic material 
derived from sexually incompatible food plants within the genus of the 
recipient plant) would be exempt unconditionally from the requirement 
of a tolerance (i.e., without any conditional criteria describing 
``significantly different dietary exposure''). The base of experience 
in relation to food safety may not justify not applying these criteria 
to sexually incompatible food plants within the same genus as the 
recipient plant. In addition, greater confusion concerning the status 
of a particular plant-pesticide may arise under the Option 2/
transcribed Unit III.B. exemption than with the Option 1/Unit III.B. 
exemption.

IV. External Review

    In developing its approach to plant-pesticides under FFDCA, EPA 
requested the advice of two scientific advisory committees on FFDCA 
related issues. 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 under 
the FFDCA. On January 21, 1994, a joint meeting of a Subpanel of the 
FIFRA Scientific Advisory Panel (SAP) and BSAC was held and EPA asked 
advice from this joint Subpanel on EPA's approach under FFDCA. The 
primary goal of the questions posed at both meetings was to identify, 
for regulatory purposes, those circumstances in which new or 
significantly different human dietary exposures to plant-pesticides 
could occur. The reports from these meetings are available in the 
public docket for this proposed rule.
    At the July 13, 1993, meeting the Agency questioned the 
subcommittee on: what information exists on which plant-pesticides in 
food might be of concern should their levels be significantly increased 
via breeding or via engineering methodologies; whether information 
exists on exposure in the diet to levels of plant-pesticides in raw 
agricultural commodities; and how plant breeders ensure that natural 
plant toxicants do not exceed acceptable levels in foods.
    The Subcommittee said:

    ``Breeders depend primarily on familiarity with food crops 
(e.g., knowledge of which crop plants have the ability to produce 
which toxicants) to ensure the safety of food from the various crop 
plant varieties. If the plant species is known to possess the 
ability to produce a toxicant (e.g., potato plants can express 
solanine), new varieties of the plant are tested for toxicant 
content (e.g., potato varieties are tested for alkaloid content). At 
this time, most of this knowledge is part of breeders' experience; 
no formal, complete data bases exist.''

    However, the Subcommittee believed that in light of breeders' 
experience and familiarity with the characteristics of crop plants and 
their sexually compatible relatives, the screening procedures employed 
in traditional breeding and known food processing considerations, 
plant-pesticides under certain conditions could be exempted from 
regulatory oversight. The Subcommittee suggested the following scheme 
to identify those groupings wherein plant-pesticides might present new 
and novel exposures. They suggested that:

    (1) 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).
    (2) Plant pesticides in plants in which the genetic material is 
derived from plants commonly used as food, but which are not members 
of the same family would be subject to review if one or more of the 
following criteria are met:
    (a) The pesticidal substance, normally produced in the inedible 
portions of the source food plant, is present in the edible portions 
of the modified host plant.
    (b) The pesticidal substance, derived from a source food plant 
almost always cooked or processed, is introduced into a food plant 
that is not cooked or processed prior to consumption.
    (c) The pesticidal substance is derived from a minor food crop 
and introduced into a major food crop.
    (3) Any pesticidal substance intentionally modified to have a 
significantly different structure, function or composition from that 
known to exist in food would require a food tolerance determination 
by the Agency.
    (4) Any pesticidal substance introduced into a food plant and 
derived from a source not used as food, except as described in (1) 
above, would require review under FFDCA.

    At the January 21, 1994, joint SAP/BSAC Subpanel meeting, the use 
of sexual compatibility (and thus sexual recombination) and/or taxonomy 
as a standard for the potential for significantly different dietary 
exposures was once again discussed. In response to the question of 
whether plants in a sexually compatible population are likely to share 
many substances or traits, the joint Subpanel agreed that sexually 
compatible plants are more likely to have a common constitution than 
unrelated plants and thus are less likely to lead to novel exposures. 
They noted that natural hybridization and selection have produced 
groups of plants which have a common gene pool. Generations of 
artificial hybridization to produce improved cultivated plants have 
tended to increase the extent of relatedness among elements of a 
broader segment of the natural diversity. In addition, modern 
techniques of genetic mapping have revealed the presence of genetic 
loci in cultivated plants that previously were considered to be present 
only in the wild species.
    In regard to the correlation of the concept of ``genus'' with 
significantly different exposures, the joint Subpanel noted that the 
taxonomic classification of a genus and the measure of sexual 
compatibility are closely interrelated. Sexual compatibility tends to 
promote genetic interchange, and this interchange leads to populations 
of plants more like each other than like groups that have been sexually 
isolated. Because plants in the same genus likely have common ancestors 
that at some period in their evolution were sexually compatible, plants 
in the same genus are more apt to be sexually compatible with each 
other than with plants from other genera. Some barriers to sexual 
compatibility exist between species in the same genus even though the 
species are similar taxonomically. However, many of these sexual 
barriers can be overcome through the use of wide cross techniques by 
breeders.
    The Agency also included a question, at the January 21, 1994, joint 
BSAC/SAP meeting, concerning an approach using a criterion based on the 
process used to modify the plant, e.g., recombinant DNA methodologies. 
As described in the report of the joint BSAC/SAP Subpanel meeting, if 
the Agency were to use this approach, it would first exempt plant-
pesticides developed through techniques other than those of modern 
biotechnology from its regulatory scope. For those plant-pesticides 
that are not exempted because they were developed through techniques of 
modern biotechnology, the exemptions proposed by the Agency would apply 
(i.e., Category 1 and 2 exemptions; see Units III.A. and III.B. of this 
preamble).
    EPA's response: EPA has utilized the suggestions of the BSAC 
Subcommittee and joint SAP/BSAC Subpanel in developing this proposal. 
In particular, EPA has utilized the concepts put forth by the advisory 
committees in developing the language of the Agency's preferred 
approaches. EPA also used the advice in developing the alternative 
options.
    EPA captured in Option 1 in Unit III.A. of this preamble the 
concept of exempting from tolerance requirements plant-pesticides 
derived from plants sexually compatible with the recipient plants as 
suggested by the first part of a two part recommendation of the BSAC 
subcommittee at the July 13, 1993, meeting; the BSAC subcommittee 
suggested exemption of plant-pesticides 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).'' This approach was reaffirmed at the January 21, 1994, 
joint SAP/BSAC meeting.
    The Agency, in creating the approach described in Unit III.B. of 
this preamble, essentially captured the second half of the scheme 
suggested by the BSAC subcommittee at the July 13, 1993, meeting; i.e., 
that under certain conditions plant-pesticides encoded by genetic 
material from food plants that are not sexually compatible can be 
exempt.
    In terms of the alternative option, at the January 1994 meeting, 
the concept of ``genus'' as a criterion of relatedness between plants 
was confirmed, and EPA used that concept to create Option 2 of Unit 
III.A. of this preamble.
    With regard to the advice of the January 21, 1994, joint SAP/BSAC 
Subpanel concerning the use of a process-based criterion in the scope, 
if the Agency were to use this approach, plant-pesticides developed 
through techniques other than those involving in vitro manipulation of 
genetic material would be exempt. In order to meet the recommendations 
of the joint Subpanel, the Agency would define this category of plant-
pesticides 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. The exemptions proposed by the 
Agency in Unit III. of this preamble would be used in concert with this 
criterion. The Agency believes this approach would meet the 
recommendations of the SAP/BSAC joint Subpanel. The Agency is 
soliciting comment on this approach (see Unit V. of this preamble).

V. Request for Comment

    The Agency requests comments on whether EPA has appropriately 
identified in this proposed exemption from the requirement of a 
tolerance those plant-pesticides that are not likely to result in new 
dietary exposures. EPA proposes to exempt from the requirement of a 
tolerance under FFDCA: (1) Plant-pesticides derived from closely 
related plants and (2) under certain conditions, plant-pesticides 
derived from food plants that are not sexually compatible with the 
recipient food plant because EPA believes tolerances for these plant-
pesticides are not necessary to protect the public health.
    Under the first exemption (Category 1), EPA has described two 
options, with Option 1 presented in the proposed regulatory text. EPA 
requests comments on these three options, specifically as to whether 
they appropriately identify, plant-pesticides that would not result in 
new dietary exposures and whether the language it uses in the two 
options to define this grouping for regulatory purposes is clear. EPA 
also requests comments on which option is most appropriate and why.
    With regard to an exemption criterion based on the process used to 
modify the plant, the Agency is soliciting comment on the joint BSAC/
SAP Subpanel advice and the utility of an approach based on that advice 
(see Unit IV. of this preamble). EPA also requests comment on whether 
the group of plant-pesticides that would be regulated under this 
approach would be equivalent to the group of plant-pesticides that 
would be regulated under Options 1, or 2.
    EPA requests comments on whether it has appropriately identified in 
the second exemption (Category 2) those plant-pesticides that should 
not be exempted because significantly different dietary exposures could 
occur from plant-pesticides derived from food plants not closely 
related to the recipient plant (i.e., substances produced in inedible 
portions of source plants but in edible portions of recipient plant, in 
immature fruits of source plant but in mature fruits of recipient 
plant, derived from plants normally cooked or processed before 
consumption and introduced into a plant not normally processed or 
cooked, or derived from a crop that is not a major crop for human 
dietary consumption and introduced into a major crop). EPA requests 
comment on whether the language it used to describe these criteria is 
sufficiently clear. It requests comment on whether cereal grains would 
be an appropriate category to be included in the definition of ``major 
crops for human dietary consumption.'' EPA also recognizes that some 
crops are highly consumed by children but not by the rest of the 
population and requests comment on whether these criteria adequately 
address categories of crops that are highly consumed by children.
    The Agency also specifically requests comment on whether it should 
include, as a qualification to the second exemption (Category 2) a 
criterion restricting the possibility that a breeder might take a 
plant-pesticide derived from a non-food plant and introduce it into a 
sexually compatible food plant (under the Category 1 exemption 
described in Unit III.A. of this preamble) and then subsequently move 
the plant-pesticide into a sexually incompatible food plant (under the 
Category 2 exemption described in Unit III.B. of this preamble). By 
bridging these two exemptions, breeders might take a plant-pesticide 
from a wild relative which is never eaten and introduce it into another 
crop that is not sexually compatible to the wild relative. The Agency 
is also requesting comment on whether this would be more critical to 
Option 1 or Option 2. The Agency is also requesting comment on whether, 
for the Category 2 exemption, a qualification should be included 
restricting the possibility that a plant-pesticide from a nonplant 
source, such as Bacillus thuringiensis, is introduced into a food plant 
and then subsequently introduced into another sexually incompatible 
food plant.

VI. Rulemaking Record and Procedures

    Any person who has registered or submitted an application for 
registration of a pesticide, under FIFRA as amended, which contains any 
plant-pesticide that falls within a category proposed for exemption may 
request within 30 days after publication of this proposed rule in the 
Federal Register that this rulemaking proposal be referred to an 
Advisory Committee in accordance with section 408(e) of the FFDCA.
    EPA has established a record for this rulemaking. Interested 
persons are invited to submit written comments on the proposed 
regulation. Comments must bear a notation indicating the document 
control number, (OPP-300368). All written comments filed in response to 
this petition will be available in the Public Response and Program 
Resources Branch, at the location listed under the ADDRESSES unit from 
8 a.m. to 4 p.m., Monday through Friday, except legal holidays.

VII. Regulatory Assessment Requirements

    The Office of Management and Budget has exempted this proposed rule 
from the requirement of review pursuant to Executive Order 12866.
    Pursuant to the requirements of the Regulatory Flexibility Act 
(Pub. L. 96-354, 94 Stat. 1164, 5 U.S.C. 601-612), the Administrator 
has determined that regulations establishing new tolerances or raising 
tolerance levels or establishing exemptions from tolerance requirements 
do not have a significant economic impact on a substantial number of 
small entities. A certification statement to this effect was published 
in the Federal Register of May 4, 1981 (46 FR 24950).
    This proposed rule is not subject to the Paperwork Reduction Act 
because it does not contain any collection of information requirements.

VIII. References

    (1) 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.
    (2) Lamb, C.J., J.A. Ryals, E.R. Ward, and R.A. Dixon. 1992. 
Emerging strategies for enhancing crop resistance to microbial 
pathogens. Bio/Technology. 10:1436-1445.

List of Subjects in 40 CFR Part 180

    Environmental protection, Administrative practice and procedure, 
Agricultural commodities, Pesticides and pests, Plants, Plant-
pesticides.

    Dated: November 15, 1994.
Carol M. Browner,
Administrator.
    Therefore, it is proposed that 40 CFR part 180 be amended as 
follows:

PART 180--[AMENDED]

    1. The authority citation for part 180 would continue to read as 
follows:

    Authority: 21 US.C. 346a and 371.

    2. By adding Sec. 180.1137 to read as follows:


Sec. 180.1137   Plant-pesticides; exemptions from the requirement of a 
tolerance.

    (a) Residues of pesticidal substances produced in living plants as 
plant-pesticides are exempt from the requirement of a tolerance if the 
genetic material that encodes for a pesticidal substance or leads to 
the production of a pesticidal substance is derived from plants that 
are sexually compatible with the recipient plant and has never been 
derived from a source that is not sexually compatible with the 
recipient plant.
    (b) Residues of pesticidal substances produced in living plants as 
plant-pesticides are exempt from the requirement of a tolerance when 
the genetic material that encodes for a pesticidal substance or leads 
to the production of a pesticidal substance is derived from plants that 
are not sexually compatible with the recipient plant if:
    (1) The genetic material that encodes for a pesticidal substance or 
leads to the production of a pesticidal substance is derived from food 
plants.
    (2) The pesticidal substances would not result in significantly 
different dietary exposures.
    (c) For the purposes of this section, the following definitions 
apply:
    Bridging crosses between plants means the utilization of an 
intermediate plant in a cross to produce a viable zygote between the 
intermediate plant and a first plant, in order to cross the plant 
resulting from that zygote with a third plant that would not otherwise 
be able to produce viable zygotes from the fusion of its gametes with 
those of the first plant. The result of the bridging cross is the 
mixing of genetic material of the first and third plant through the 
formation of an intermediate zygote.
    Food plant means a plant which, either in part or in toto, is used 
as food by humans.
    Genetic material necessary for the production means:
    (1) Genetic material that encodes for a pesticidal substance or 
leads to the production of a pesticidal substance.
    (2) Regulatory regions.
    It does not include noncoding, nonexpressed nucleotide sequences.
    Genetic material that encodes for a pesticidal substance or leads 
to the production of a pesticidal substance does not include regulatory 
regions or noncoding, nonexpressed nucleotide sequences.
    Living plant means a plant that is alive, including periods of 
dormancy, and all viable plant parts/organs involved in the plant's 
life cycle.
    Major crops for human dietary consumption means wheat, corn, 
soybeans, potatoes, oranges, tomatoes, grapes, apples, peanuts, rice, 
beans, and any other crop that the Agency has determined is a major 
crop for human dietary consumption.
    Noncoding, nonexpressed nucleotide sequences means the nucleotide 
sequences are not transcribed and are not involved in gene expression. 
Examples of noncoding, nonexpressed nucleotide sequences include 
linkers, adapters, homopolymers, and sequences of restriction enzyme 
recognition sites.
    Plant-pesticide means a pesticidal substance that is produced in a 
living plant and the genetic material necessary for the production of 
the substance, where the substance is intended for use in the living 
plant.
    Recipient plant means the plant into which the plant-pesticide is 
introduced and in which the plant-pesticide is produced.
    Regulatory region means genetic material that controls the 
expression of the genetic material that encodes for a pesticidal 
substance or leads to the production of a pesticidal substance. 
Examples of regulatory regions include promoters, enhancers, and 
terminators.
    Result in significantly different dietary exposure means:
    (1) The pesticidal substance is produced in inedible portions of 
the source food plant, but, in the recipient plant, the pesticidal 
substance is present in the plant's edible portion.
    (2) The pesticidal substance is produced in the immature, but not 
in the mature, edible portions of the source food plant, but, in the 
recipient plant, the pesticidal substance is present in the mature, 
edible portions.
    (3) The pesticidal substance is from a source food plant normally 
cooked or processed prior to consumption and is produced in a recipient 
plant that is not normally cooked or processed prior to consumption.
    (4) The pesticidal substance is derived from a source food plant 
that is not a major crop for human dietary consumption and is 
introduced into a recipient plant that is a major crop for human 
dietary consumption.
    Sexually compatible, when referring to plants, means capable of 
forming a viable zygote through the fusion of two gametes, including 
the use of bridging crosses and/or wide crosses between plants.
    Source food plant means the donor of the genetic material that 
encodes for a pesticidal substance or leads to the production of a 
pesticidal substance.
    Wide crosses, between plants, means to facilitate the formation of 
viable zygotes through the use of surgical alteration of the plant 
pistil, bud pollination, mentor pollen, immunosuppressants, in vitro 
fertilization, pre- 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.

[FR Doc. 94-28823 Filed 11-22-94; 8:45 am]
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