[Federal Register Volume 62, Number 95 (Friday, May 16, 1997)]
[Proposed Rules]
[Pages 27132-27142]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-12784]


      

[[Page 27131]]

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Part VI





Environmental Protection Agency





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40 CFR Part 180



Plant-Pesticides, Supplemental Notice; Proposed Rule



Plant-Pesticides; Nucleic Acids; Proposed Rule



Plant-Pesticides; Viral Coat Proteins; Proposed Rule

  Federal Register / Vol. 62, No. 95 / Friday, May 16, 1997 / Proposed 
Rules  

[[Page 27132]]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-300368A; FRL-5717-2]
RIN 2070-AC02


Plant-Pesticides; Supplemental Notice of Proposed Rulemaking

AGENCY: Environmental Protection Agency (EPA).

ACTION: Supplemental notice of proposed rulemaking.

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SUMMARY: This document announces the availability of information for 
additional public comment regarding a proposed exemption from the 
requirement of a tolerance under the Federal Food, Drug, and Cosmetic 
Act (FFDCA) for pesticidal substances that are a component of certain 
plant-pesticides, i.e., those plant-pesticides that are derived from 
closely related plants. Comments on this document may also affect EPA's 
final determination on a proposed exemption under the Federal 
Insecticide, Fungicide, and Rodenticide Act (FIFRA) for this same 
category of plant-pesticides. In 1994, EPA proposed to exempt from the 
requirement of a tolerance the pesticidal substance portion of plant-
pesticides moved between closely related plants because a tolerance 
would not be necessary to protect the public health. Since publication 
of the proposal, Congress enacted the Food Quality Protection Act 
(FQPA) which amended FFDCA and FIFRA. EPA is issuing this document 
today to provide the public with an opportunity to comment on EPA's 
analysis of how certain FQPA amendments to FFDCA and FIFRA apply to the 
proposed exemption from the requirement of a tolerance for pesticidal 
substances moved between closely related plants. EPA believes that it 
considered most of the substantive issues associated with the FQPA 
amendments when it issued the proposals in 1994. EPA is thus, in this 
document, specifically seeking comment only on its evaluation of the 
requirements imposed by FQPA that the Agency did not address in the 
proposals.

DATES: Comments, identified by the docket control number ``OPP-
300368A,'' must be received on or before June 16, 1997.

ADDRESSES: By mail, submit written comments to: Public Information and 
Records Integrity Branch, Information Resources and Services Division 
(7506C), Office of Pesticide Programs, Environmental Protection Agency, 
401 M St., SW., Washington, DC 20460. In person deliver comments to: 
Rm. 1132, Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA.
    Comments and data may also be submitted electronically by following 
the instructions under Unit IV.D. of this document. No Confidential 
Business Information (CBI) should be submitted through e-mail.

FOR FURTHER INFORMATION CONTACT: By mail: Elizabeth Milewski, Office of 
Science, Coordination and Policy, Office of Prevention, Pesticides and 
Toxic Substances (7101), Environmental Protection Agency, 401 M St., 
SW., Washington, DC 20460, Telephone: (202) 260-6900, e-mail address: 
[email protected].

SUPPLEMENTARY INFORMATION:

I. Introduction

    EPA issued in the November 23, 1994 Federal Register a package of 
five separate Federal Register proposals (59 FR 60496, 60519, 60535, 
60542 and 60545) (FRL-4755-2, FRL-4755-3, FRL-4758-8, FRL-4755-5, and 
FRL-4755-4) which together described EPA's approach to substances 
produced in plants that enable the plants to resist pests or disease. 
EPA's package of proposals indicated that these substances are 
pesticides under section 2 of FIFRA (7 U.S.C. 136(u)) if they are 
``intended for preventing, destroying, repelling, or mitigating any 
pest'' or if they are ``. . . intended for use as a plant regulator, 
defoliant, or desiccant'' regardless of whether the pesticidal 
capabilities evolved in the plants or were introduced by breeding or 
through the techniques of modern biotechnology. These substances, and 
the genetic material necessary to produce them, were designated 
``plant-pesticides'' by EPA in the November 23, 1994 Federal Register 
notices. The proposals defined a ``plant-pesticide'' as ``a pesticidal 
substance that is produced in a living plant and the genetic material 
necessary for the production of the pesticidal substance where the 
pesticidal substance is intended for use in the living plant'' (59 FR 
at 60534).
    One of the five documents (59 FR 60535) proposed to exempt the 
pesticidal substance portion of plant-pesticides moved between closely 
related plants from the FFDCA (21 U.S.C. 346a) requirement of a 
tolerance based upon an evaluation of the potential for new dietary 
exposures to the substances when they are produced in plants, or in 
plant parts, used as food or feed. EPA proposed in the same Federal 
Register (59 FR at 60537) to define closely related plants as plants 
that are sexually compatible. In the proposal, 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. EPA stated in the proposed exemption that 
a tolerance is not necessary to protect the public health for these 
pesticidal substances because no new dietary exposures are likely to 
occur for pesticidal substances moved between sexually compatible 
plants. For pesticidal substances in this category, many years of 
experience of human use suggest that under normal dietary conditions 
these pesticidal substances present negligible risk. Specifically, EPA 
proposed that ``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'' (59 FR at 60542).
    This supplemental notice addresses the pesticidal substance portion 
of plant-pesticides produced in food plants. A companion supplemental 
notice issued elsewhere in today's Federal Register addresses the 
proposed exemption for the nucleic acid component of plant-pesticides 
with regard to the FQPA amendments to FFDCA.
    Because FQPA modified FIFRA (7 U.S.C. 136 et seq.) by incorporating 
the FFDCA safety standard into the FIFRA test for determining whether a 
pesticide poses an unreasonable adverse effect, comments on these 
supplemental notices may also affect EPA's final determination on the 
proposed exemption (59 FR 60519) under FIFRA for plant-pesticides that 
are derived from plants sexually compatible with the recipient plant.
    EPA is issuing this supplemental notice, as well as the companion 
supplemental notice on nucleic acids to ensure that the public has had 
adequate opportunity to comment on certain new considerations raised by 
the FQPA amendments to FFDCA as these considerations relate to the 
proposed exemption from tolerance for residues of pesticidal substances 
derived from sexually compatible plants. In evaluating a pesticide 
chemical residue for exemption from FFDCA tolerance requirements, EPA 
must now explicitly address certain factors, and make a determination 
that there is a reasonable certainty that aggregate exposure to the

[[Page 27133]]

residue will cause no harm to the public. The factors to be considered 
are iterated in Unit II. of this supplemental notice. EPA's evaluation 
of these factors relative to the proposed exemption (59 FR 60535) is 
contained in Unit IV. of this supplemental notice. Consistent with 
FFDCA section 408(c)(2)(B), EPA has reviewed the available scientific 
data and other relevant information in support of this action. In 
today's supplemental notice, EPA requests comment only on the new 
conclusions identified in Unit V.C. of this supplemental notice.
    In light of FQPA, EPA is engaged in a process, including 
consultation with registrants, states, and other interested 
stakeholders, to make decisions on the new policies and procedures that 
will be appropriate as a result of enactment of FQPA. In establishing 
this exemption from the requirement of a tolerance for pesticidal 
substances derived from sexually compatible plants, EPA does not intend 
to set precedents for the application of section 408 and the new safety 
standard to other tolerances and exemptions. This exemption from the 
requirement of a tolerance will not restrict EPA's options with regard 
to general procedures and policies for implementation of the amended 
FFDCA section 408.

II. Statutory Authority

    Under FFDCA, EPA regulates pesticide chemical residues by 
establishing tolerances limiting the amounts of residues that may be 
present in food, or by establishing exemptions from the requirement of 
a tolerance for such residues. Pesticide chemical residues subject to 
regulation under FFDCA are defined by reference to the definition of 
pesticide under FIFRA. FFDCA section 201(q)(1) defines a ``pesticide 
chemical residue'' to mean the residue in or on food of a pesticide 
chemical or other added substance resulting primarily from the 
metabolism or degradation of a pesticide chemical (21 U.S.C. 
321(q)(2)). A ``pesticide chemical'' means ``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 authorizes EPA to regulate the sale and distribution of 
pesticides in the United States and to exempt a pesticide from the 
requirements of FIFRA if it is not of a character requiring regulation 
(7 U.S.C. 136a(a) and 136w(b)). 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)).
    FQPA amends both FFDCA and FIFRA. FQPA, which took effect on August 
3, 1996, among other things, amends FIFRA such that a registration 
cannot be issued for a pesticide to be used on or in food unless the 
residue of the pesticide in food qualifies for a tolerance or exemption 
from the requirement for a tolerance. FQPA modified FIFRA section 2(bb) 
by incorporating the FFDCA section 408 safety standard into the test 
for determining whether a pesticide poses an unreasonable adverse 
effect (7 U.S.C. 136(bb)). FIFRA section 2(bb) defines the term 
``unreasonable adverse effects on the environment'' to mean (1) any 
unreasonable risk to man or the environment, taking into account the 
economic, social, and environmental costs and benefits of the use of 
any pesticide, or (2) a human dietary risk from residues that result 
from a use of a pesticide in or on any food inconsistent with the 
standard under section 408 of the FFDCA. Thus, a pesticide used in or 
on food that does not meet the FFDCA section 408 safety standard also 
would pose an unreasonable adverse effect under FIFRA and would not 
qualify for an exemption from the requirements of FIFRA under FIFRA 
section 25(b)(2).
    FQPA amends FFDCA section 408(c)(2)(A)(i) to allow EPA to establish 
an exemption from the requirement of a tolerance for a ``pesticide 
chemical residue'' only if EPA determines that the exemption is 
``safe'' (21 U.S.C. 346a(c)(2)(A)(i)). Section 408(c)(2)(A)(ii) 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, but does not include 
occupational exposure. In establishing an exemption from the 
requirement of a tolerance, FFDCA section 408(c), like the statute 
prior to FQPA, does not require EPA to consider benefits that might be 
associated with use of the pesticide chemical.
    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 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). Section 408(b)(2)(D) specifies 
other, general factors EPA is to consider in establishing an exemption. 
Section 408(c)(3)(B) 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 
(21 U.S.C. 346a(c)(3)(B)).
    Specifically, EPA must consider the following in deciding whether 
to grant an exemption:
    1. The validity, completeness, and reliability of the available 
data from studies of the pesticide chemical and pesticide chemical 
residue.
    2. Nature of any toxic effect shown to be caused by the pesticide 
chemical or residues in studies.
    3. Available information concerning the relationship of the results 
of such studies to human risk.
    4. Available information concerning the dietary consumption 
patterns of consumers (and major identifiable subgroups of consumers).
    5. Available information concerning the cumulative effects of such 
residues and other substances that have a common mechanism of toxicity.
    6. Available information concerning the aggregate exposure levels 
of consumers to the pesticide chemical residue and to other related 
substances, including dietary exposure and non-occupational exposures.
    7. Available information concerning the variability of the 
sensitivities of major identifiable subgroups of consumers.
    8. Such information as the Administrator may require on whether the 
pesticide chemical may have an effect in humans that is similar to an 
effect produced by a naturally-occurring estrogen or other endocrine 
effects.
    9. Safety factors which in the opinion of experts qualified by 
scientific training and experience to evaluate the safety of food 
additives are generally recognized as appropriate for the use of animal 
experimentation data (21 U.S.C. 346a(b)(2)(D).
    Additionally, with respect to exposure of infants and children, 
consistent with section 408(b)(2)(C), EPA must assess the risk of the 
pesticide based on available information concerning:
    1. Consumption patterns that are likely to result in 
disproportionately high consumption of food with pesticide residues.
    2. Special susceptibility of infants and children to such residues.
    3. Cumulative effects of residues with other substances that have a 
common

[[Page 27134]]

mechanism of toxicity (21 U.S.C. 346a(b)(2)(C) and (c)(2)(B)).

III. Summary of Proposed Regulations

    This supplemental notice affects three of the proposals that 
appeared in the November 23, 1994 Federal Register: (1) A proposal 
under FFDCA to exempt from the requirement of a tolerance, residues of 
the pesticidal substance portion of any plant-pesticide that is derived 
from a plant that is sexually compatible with the recipient plant (59 
FR 60535); (2) a companion proposal (59 FR 60542) under FFDCA to exempt 
``residues of nucleic acids produced in living plants as part of a 
plant-pesticide''; and (3) a proposal (59 FR 60519) under FIFRA to 
exempt from most of the requirements of FIFRA, plant-pesticides derived 
from a plant that is sexually compatible with the recipient plant.
    In the November 23, 1994 Federal Register, the Agency proposed to 
exempt from the FFDCA requirement of a tolerance (59 FR 60535) and most 
requirements of FIFRA (59 FR 60519) pesticidal substances moved between 
plants that are closely related. EPA discussed two options for 
describing plants that are closely related: (1) Plants that are 
sexually compatible, or (2) plants that are within the same taxonomic 
genus or are sexually compatible. Sexual compatibility would include 
use of techniques such as wide and bridging crosses. EPA's preferred 
approach for describing closely related plants was the option based on 
sexual compatibility alone. Thus, EPA proposed that plant-pesticides 
derived from plants that are sexually compatible would be exempt from 
most FIFRA requirements, and residues of pesticidal substances that are 
derived from sexually compatible plants would be exempted from the 
FFDCA requirement of a tolerance.
    The rationale underlying the proposed exemptions is that plants in 
a sexually compatible population are likely to have the same 
information encoded in their genetic material and to share traits in 
common. Groups of plants having a common pool of genetic material have 
resulted from the processes of evolution. Generations of directed 
breeding to produce improved crops for cultivation have tended to 
increase the relatedness of agricultural crop plants and reduce the 
variability in the common pools of genetic information of crop plants. 
Because sexually compatible plants share a common pool of genetic 
material, movement of genetic material encoding pesticidal substances 
between plants in a sexually compatible population is unlikely to 
result in novel environmental or dietary exposures. If a crop plant 
normally produces a pesticidal substance, humans consuming the crop, 
and organisms coming into contact with the plant, have been exposed to 
that substance in the past, perhaps over long periods of time. No new 
exposures are likely to occur. Because of the high degree of 
relatedness among plants comprising sexually compatible populations, 
the potential for new human exposures, either dietary or environmental, 
is low for pesticidal substances in sexually compatible plants or plant 
parts used as food or feed. Under the exemptions for plant-pesticides 
derived from sexually compatible plants, EPA exempts from the FFDCA 
requirement of a tolerance those plant-pesticides that are normally a 
component of (not new to) the recipient plant. EPA believes that crops 
grown for food in the U.S. today would qualify for this exemption (59 
FR at 60535 and 60542) based on the standard of relatedness as 
described by sexual compatibility.
    The proposed exemption from the requirement of a tolerance (59 FR 
60535) was examined 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. Although very large 
numbers of plant varieties are used and large numbers of varieties are 
introduced into agricultural use each year, there are only a few 
examples of plant varieties causing food safety concerns.
    Based on these considerations, and as required by the FFDCA prior 
to enactment of the FQPA, EPA concluded that plant-pesticides found in 
the current food supply would present no hazard under potential use 
conditions and, hence, a tolerance would not be necessary to protect 
the public health.
    EPA's alternative option for describing relatedness in plants (59 
FR at 60537) used both sexual compatibility and taxonomy (genus). Under 
this alternative option, if a plant-pesticide was derived from a plant 
classified in the same genus as the recipient plant or if the donor 
plant was sexually compatible with the recipient plant, that plant-
pesticide would be exempt. The assumption underlying this alternative 
option was that the taxonomic grouping of genus correlated to a 
relatively high degree of relatedness. This option was not EPA's 
preferred approach, because even though plants grouped within a genus 
may be fairly closely related, certain species within a genus may never 
have contributed traits to plants currently found in the food supply 
and thus no known dietary exposure exists for traits from such plants. 
Therefore, EPA preferred the option based on sexual compatibility alone 
which EPA believes best describes plant-pesticides found in the food 
supply.
    In the 1994 Federal Register (59 FR 60535), EPA also proposed to 
exempt from the requirement of a tolerance a second category of 
pesticidal substances. This second category consists of pesticidal 
substances that are derived from food plants that are not closely 
related to the recipient plant but which would not result in 
significantly different dietary exposures when produced in the 
recipient plant. This second category will not be addressed in this 
supplemental notice but will be addressed in a separate Federal 
Register in the future.

IV. Risk Assessment and Safety Determinations

A. Risk Assessment in the 1994 Proposal

    This section reviews the analysis that EPA used to support its 1994 
proposal (59 FR 60535) to exempt pesticidal substances derived from 
sexually compatible plants from the requirement of a food tolerance 
under the FFDCA. EPA also relied upon the analysis in the 1994 FFDCA 
proposal to evaluate human dietary risks in support of its proposal (59 
FR 60519) to exempt plant-pesticides from sexually compatible plants 
from most FIFRA requirements. Non-dietary human risks from exposure to 
such pesticidal substances were examined under the analysis for the 
proposed FIFRA exemption and are discussed in this supplemental notice 
only as they pertain to the dietary risks.
    When EPA proposed in 1994 to exempt residues of pesticidal 
substances that are derived from sexually compatible plants from the 
requirement of a tolerance (59 FR 60535), it concluded that a food 
tolerance for such substances would not be necessary to protect the 
public health because such substances presented no significant hazards 
under potential use conditions. EPA based this conclusion upon its 
analysis of potential dietary exposure, hazard and risk from 
consumption of plants that contain these substances. EPA recognized and 
relied on the long history of human experience with growing and 
consuming plants for food and with the procedures of plant breeding. 
Plant breeding combines the scientific knowledge of experimental 
laboratory disciplines such as plant

[[Page 27135]]

physiology, plant genetics, and phytopathology into a practical field 
science that develops new plant cultivars for use in agriculture. EPA 
has used these bases of knowledge and experience in its estimation of 
exposures and hazards of the residues of pesticidal substances 
addressed by this supplemental notice as well as for the 1994 proposal.
    EPA concluded in the 1994 proposal (59 FR 60535) that the vast 
majority of plant varieties developed by plant breeders using traits 
from sexually compatible plants produce foods that are safe for human 
consumption. This conclusion is based on the experience of consuming 
crops resulting from scientific breeding as well as the historical 
consumption of crops since the prehistorical origins of agriculture. 
These foods undoubtedly contain(ed) pesticidal substances (and the 
genetic material necessary to produce them) and share a history of safe 
consumption. In addition, appropriate processing procedures are widely 
known and are routinely used by consumers in preparation of food from 
such sources, including those foods which require specific processing/
preparation steps to avoid dietary problems.
    In the 1994 proposal, EPA stated that 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, some of which might be pesticidal in function, are known. 
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 documented cases of new 
plant cultivars causing food safety problems despite the large numbers 
of new varieties introduced into commerce each year, is a reflection of 
the effectiveness of this process (59 FR at 60538).
    Plant varieties for the food market have been developed by breeders 
seeking better products, higher yields, and other desirable crop 
characteristics. In this process, it has been common agricultural 
practice to move traits among sexually compatible food plant varieties 
as well as to introduce traits from sexually compatible wild relatives 
into plant varieties that are used as food plants. This type of 
breeding process has been used on most sexually compatible crop plants, 
and tended to increase the extent of relatedness among plant varieties 
in agricultural crops. The 1994 proposal 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. The sexually compatible, wild relatives of 
cultivated plants that are used in this process do not themselves 
necessarily have any history of human consumption but have safely 
contributed traits through sexual recombination to cultivars on the 
market. For example, wild species of tomatoes have been used, in plant 
breeding, as a source of increased resistance to economically important 
diseases in tomato (Ref. 1). Sexually compatible crop varieties of the 
same plant species are also crossed with each other to achieve better 
pest resistance in their progeny. Food plant varieties developed in 
this way have been introduced, cultivated, and consumed by humans for 
many years with very few observed adverse affects (59 FR at 60538).
    If a food plant or its close relative normally produces a 
pesticidal substance, humans have likely been exposed to that substance 
in the past. Experience with both growing agricultural plants and 
consuming food from plants which undoubtedly contain pesticidal 
substances demonstrates the safety of the current food supply, 
including substances in the food supply that may be plant-pesticides. 
The Agency believes this experience combined with the knowledge of 
plant genetics, plant physiology, phytopathology and plant breeding are 
the appropriate considerations in evaluating the potential risks of 
residues of the pesticidal substances proposed for the tolerance 
exemption (59 FR 60535).
    The residues of the pesticidal substances that are the subject of 
the proposed exemption have evolved in populations of sexually 
compatible plants. They are part of the metabolic cycles of these 
plants. They are thus subject to the processes of degradation and decay 
that all organic matter undergoes. They are not likely to persist in 
the environment nor bioaccumulate in the tissues of living organisms. 
Because they do not persist, the potential for new exposures to the 
residues to occur, beyond direct physical exposures to the plant, would 
be limited. As noted in the proposal (59 FR at 60516), plant-pesticides 
present negligible exposure of the pesticidal substances to humans 
outside the dietary route because the substances are in the plant 
tissue and thus are found either within the plant or in close proximity 
to the plant. In contrast, applied synthetic chemicals have much 
greater potential for new dietary exposures. Prior to the use of 
synthetic pesticides, there may be very little scientific experience 
with the new pesticidal substance or even a complete lack of known 
dietary exposure to the pesticidal substance.
    EPA evaluated the potential risks of a pesticidal substance derived 
from a closely-related plant relative based upon the unique 
characteristics of plant-pesticides. In evaluating the pesticidal 
substance component of plant-pesticides, EPA took into account 
available knowledge from a number of scientific disciplines. 
Experimental data in the area of plant genetics provided an estimate of 
the exchange, between plants, of genetic material that is necessary for 
the production of the pesticidal substances. 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 production of such 
substances. This information provided a basis for EPA's estimation of 
the physiological limitations to production of substances that may have 
a pesticidal effect. The Agency also used experimental data derived 
from the science of phytopathology to characterize the disease and pest 
resistant mechanisms known to occur in plants. All of these bases of 
knowledge and experience were integral to EPA's assessment of exposures 
and hazards associated with pesticidal substances.
    EPA considered whether there are variations in the levels of 
pesticidal substances that are the subject of the proposed exemption 
(59 FR 60535) within and between plant varieties, and thus variation in 
exposure that might affect the Agency's determination that pesticidal 
substances that are the subject of the proposed exemption present 
negligible risk. The amount of pesticidal substance produced by plants 
normally varies among members of a closely related population (even 
within a single variety), because of the effects of conditions such as 
genetic constitution and environment (e.g., weather) on trait 
expression. This variation in turn leads to differences in the levels 
and types of exposure to the pesticidal substance. Since such variation 
is a natural phenomenon common to all plants, humans have been and are 
always exposed to varying levels of the pesticidal substances that are 
the subject

[[Page 27136]]

of this exemption when they consume food from plants.
    EPA also considered the constraints upon the extent to which 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, uniformity of seed drop) in 
developing marketable plant varieties. Plants have, as do all 
organisms, only a limited capacity to express a particular trait 
without an unacceptable drain on energy reserves. Greatly increased 
levels of a pesticidal substance would, in general, only be 
accomplished at the expense of expressing other agriculturally 
desirable traits (e.g., yield). EPA does not believe that levels of 
pesticidal substances that are the subject of the proposed exemption 
(59 FR 60535) will be increased to a point that will result in an 
adverse dietary effect. EPA has extensively evaluated whether 
quantitative changes in levels of the pesticidal substances that are 
the subject of the proposed exemption would warrant regulation by the 
setting of a food tolerance. EPA has determined that changes in the 
levels of these pesticidal substances present a reasonable certainty of 
causing no harm because the highest levels likely to be attained in 
plants are not likely to result in overall significantly different 
dietary exposures. EPA does not anticipate that attempts to increase 
the levels of these pesticidal substances would lead to a significantly 
different spectrum of exposure than that with which there is 
substantial experience.
    The evaluation of potential dietary risk associated with the 
pesticidal substances that are the subject of the proposed exemption 
(59 FR 60535) were considered within the context of the food supply and 
dietary consumption patterns. The residues of pesticidal substances 
that are the subject of the proposed exemption are components of a 
human diet. In developing the proposal, the Agency considered that the 
diet includes all of the food items that are customarily eaten by human 
populations or subpopulations. The consumption of food plants is part 
of a balanced and varied diet. Individuals recognize and are familiar 
with the plant crop derived food they consume and, based on prior 
experience with food, individuals avoid potential exposures to foods 
containing substances they know, either through personal experience or 
through acquired knowledge, cause them problems. Since the proposed 
exemption will not affect the current pattern of exposure to the 
pesticidal substances that are the subject of the proposed exemption, 
the current method whereby sensitive individuals recognize and avoid 
foods known to cause them problems will not be altered. As noted in the 
proposal (59 FR at 60505), ``consumer experience with the handling and 
preparation of food from these plants contributes to the safety of food 
from these plants.
    The approach used by EPA to evaluate the dietary risk posed by the 
pesticidal substance component of plant-pesticides derived from 
sexually compatible plants (59 FR 60535) differs somewhat from the 
approach the Agency uses for other pesticides. For more traditional 
pesticides, EPA's risk evaluation relies on, for the most part, data 
generated by testing in laboratories using representative, single 
species animal model systems to estimate risk end-points such as 
toxicity and carcinogenicity. Conclusions from data generated from 
these single species testing systems are then extrapolated to 
conclusions concerning hazards to humans, including conclusions on 
dietary hazards presented by chemical pesticide residues in crops and 
domestic animals used as food sources for humans. Mathematical models, 
as well as experimental data, on pesticide residues, provide 
information on exposure. Exposure and hazard considerations are 
combined to quantify the potential risk associated with a traditional 
pesticide. Safety factors are often used in the risk assessment as an 
added measure of caution when toxicity data from surrogate animal 
testing are used to estimate human toxicity. Such safety factors are 
not necessary in risk assessment when data on human effects is directly 
available, as is the case for the proposed exemption from the 
requirement of a tolerance for residues of pesticidal substances 
derived from sexually compatible plants.
    The approach to assessing risk described in the preceding paragraph 
is appropriate for analyzing risks posed by pesticide residues from 
pesticides such as chemical pesticides, pesticides extracted from 
plants, and some types of non-exempt plant-pesticides. For example, 
some chemicals used as pesticides may have no history of safe dietary 
consumption because they were created by humans and are synthetic. 
Single species animal testing may provide the only data on the effect 
of these pesticides on living organisms. Chemical pesticides that do 
not occur in nature, but are a product of human intervention, may not 
necessarily be subject to the processes by which biotic substances are 
degraded or cycled in nature. Thus, they may persist in the environment 
for long periods of time and may bioaccumulate in the tissues of living 
organisms.
    The risk assessment methodology appropriate for such chemicals is 
not appropriate for the pesticidal substances that evolved in the plant 
and are the subject of the proposed exemption (59 FR 60535). Plant-
pesticides derived from sexually compatible plants differ from more 
traditional pesticides in a number of ways. As noted in the proposal 
(59 FR at 60511), the major characteristic of plant-pesticides that is 
different from traditional pesticides is that the plant itself produces 
the pesticidal substance rather than the pesticide being applied to the 
plant. Thus, the exposure pattern may be very different for plant-
pesticides than for traditional pesticides both because of how the 
pesticide is produced and the biology of plants. . . . the potential 
for causing adverse health effects may be more circumscribed than for 
traditional pesticides because, in many cases, the only significant 
route of human exposure may be oral.'' Several conditions limit the 
potential for exposure to plant-pesticides as compared to traditional 
pesticides. These include that: (1) Exposure with plant-pesticides 
would be primarily through one route (dietary), (2) production of the 
pesticidal substance is limited by the plant's physiological 
constraints, (3) plant-pesticides derived from sexually compatible 
plants are integral parts of a plant's metabolism and thus are 
compatible with the biological processes of other organisms. Because of 
their biotic nature, the pesticidal substances that are the subject of 
the proposed exemption do not persist in the environment nor do they 
bioaccumulate in the tissues of living organisms. Thus, the number of 
routes of exposure that must be considered in performing a risk 
assessment are reduced since the primary route of exposure to plant-
pesticides will be ingestion of plant tissues that contain the 
pesticidal substances that are the subject of the proposed exemption.
    When EPA proposed to exempt residues of pesticidal substances 
derived from sexually compatible plants from the requirement of a 
tolerance (59 FR 60535), it considered health risks to the general 
population, which included infants and children. Children and infants, 
like adults, have been consuming food containing the pesticidal 
substances that are the subject of the proposed exemption. There is no 
evidence such pesticidal substances, as a component of food, present a 
different level of dietary risk for infants and children than they 
would for the adult

[[Page 27137]]

population. EPA's risk assessment in the proposed exemption included 
subgroups as part of the general population, (i.e., infants and 
children and the effects of culture on diet), and allowed for 
consumption pattern differences of such subgroups. For infants and 
children and other subgroups, EPA relied on the human experience base 
that it describes in summary form in this supplemental notice. On the 
basis of its analysis, EPA determined that a tolerance would not be 
necessary to protect the health of infants and children because 
pesticidal substances derived from sexually compatible plants would not 
pose significant new dietary exposures and experience indicates that 
plant-pesticides that are the subject of the exemption present no 
hazard under the use conditions.

B. Risk Assessment in Light of Amendment to FFDCA

    After EPA issued its proposed exemption from the requirement of a 
tolerance for plant-pesticides derived from sexually compatible plants 
(59 FR 60535), Congress enacted FQPA and amended certain FFDCA 
provisions governing pesticide chemical residues and FIFRA provisions 
governing pesticides (See Unit II. of this supplemental notice). 
Congress revised the specific wording of the section 408 standard for 
exemptions and provided more specific guidance regarding some of the 
factors that EPA should consider in establishing such exemptions (see 
Unit II. of this supplemental notice). When EPA proposed the exemption 
for residues of pesticidal substances derived from sexually compatible 
plants (59 FR 60535), it considered most of the safety factors spelled 
out in FQPA even though the Agency may not have explicitly discussed 
all those factors using the terminology specified in the FQPA 
amendments. This supplemental notice describes how the Agency took 
account of most of the FQPA factors in issuing its 1994 proposal to 
exempt pesticidal substances derived from sexually compatible plants 
and indicates which factors were considered in that proposal. The 
information the Agency relied on in considering these factors is part 
of the public record which was available to the public when EPA issued 
the proposed exemption from the requirement of a food tolerance. The 
supplemental notice also identifies the factors that were not 
considered in the proposal. Because FQPA amended FIFRA by incorporating 
the section 408 safety standard, commenters should be aware that 
comments on this supplemental notice may also affect EPA's final 
determination on the proposed exemption (59 FR 60519) under FIFRA for 
plant-pesticides that are derived from plants sexually compatible with 
the recipient plant.
    1. Validity, completeness, and reliability of available data. EPA 
considered in 1994 the validity, completeness, and reliability of the 
available data with regard to pesticidal substances derived from 
sexually compatible plants in the proposals (59 FR 60519 and 60535) and 
has summarized the evaluation in Unit IV.A. of this supplemental 
notice.
    2. Nature of toxic effect. EPA in 1994 considered the nature of the 
toxic effects caused by pesticidal substances derived from sexually 
compatible plants in the proposals (59 FR 60519 and 60535) and has 
summarized its evaluation in Unit IV.A. of this supplemental notice.
    3. Relationship of studies to humans. EPA in 1994 considered the 
available information concerning the relationship to humans of toxic 
effects of pesticidal substances that are the subject of the proposed 
exemption when it issued the proposals (59 FR 60519 and 60535) and has 
summarized that evaluation in Unit IV.A. of this supplemental notice. 
EPA based its evaluation on the history of human consumption of food 
derived from crop plants, and from products such as meat and milk from 
animals that consume forage and other crops (e.g., corn and other 
grains) that contain residues of pesticidal substances that are the 
subject of the proposed exemption (59 FR 60535). Because knowledge of 
human consumption of food derived from sexually compatible plants was 
available and adequately addressed the issues of hazard and exposure, 
the Agency did not use, for the proposed exemption (59 FR 60535), data 
generated in the laboratory through animal testing.
    4. Dietary consumption patterns. EPA considered in the 1994 
proposal (59 FR 60535) the available information on the varying dietary 
consumption patterns of major identifiable consumer subgroups as it 
pertains to pesticidal substances derived from sexually compatible 
plants. The Agency's evaluation is summarized in Unit IV.A. of this 
supplemental notice.
    5. Available information concerning cumulative effects of the 
pesticide chemical residue and other substances that have a common 
mechanism of toxicity. In the 1994 proposal (59 FR 60535), EPA examined 
available information on the cumulative effect of pesticidal substances 
derived from sexually compatible plants as well as other substances 
present in food that may have a common mechanism of toxicity with such 
pesticidal substances. EPA summarizes this information and its analysis 
in Unit IV.A. of this supplemental notice.
    With regard to the pesticidal substance itself, the proposal notes 
(59 FR at 60505) that this exemption ``is based upon the premise that 
new dietary exposures would not likely arise for plant-pesticides 
produced in food plants if the genetic material leading to the 
production of the plant-pesticide is derived from sexually compatible 
plants.'' Thus, the proposal would exempt residues of pesticidal 
substances that are normally components of (not new to) food from 
plants in sexually compatible populations. As discussed in Unit IV.A. 
of this supplemental notice, differences in the levels of pesticidal 
substances present may occur between plants in a sexually compatible 
population. EPA determined in the proposals that changes in the levels 
of these pesticidal substances are not likely to result in overall 
significantly different dietary exposures. As noted in the proposal (59 
FR at 60538) ``[e]xtensive use and experience show the safety of foods 
containing these substances.'' If, however, information becomes 
available that indicates this finding is no longer consistent with the 
FFDCA exemption standard for a pesticidal substance in this category, 
EPA will consider the validity of the new information and act to amend 
this tolerance exemption as necessary to protect the public health. In 
the 1994 proposal (59 FR at 60535), EPA is proposing a requirement that 
any person who sells or distributes plant-pesticides that have been 
exempted must report to EPA any information that comes into their 
possession regarding unreasonable adverse effects of an exempted plant-
pesticide on human health or the environment.
    With regard to substances in food that may share a common mechanism 
of toxicity with the residues of the pesticidal substances that are the 
subject of the proposed exemption (59 FR 65035), EPA considered the 
effects of these substances when it addressed the safety of food. Food 
from plants has thousands of constituents. Thus, EPA cannot rule out 
the possibility that the foods humans consume would also contain 
substances that have a common mechanism of action with the pesticidal 
substances that are the subject of the proposed exemption. However, 
because sexually compatible plants share a common pool of genetic 
material, any substances that may share a common mechanism of toxicity 
with the pesticidal substances that are the subject

[[Page 27138]]

of the proposed exemption (59 FR 60535) are normally components of (not 
new to) food from plants in sexually compatible populations. As 
discussed in the 1994 preamble and supporting record for the proposal, 
food from plants in sexually compatible populations have historically 
been 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 indicates that any cumulative effects 
between substances in food that may have a common mechanism of toxicity 
with the pesticidal substances that are the subject of the proposed 
exemption present a very low probability of human risk. The analysis 
made in the preceding paragraph concerning potential increases in 
levels of pesticidal substances apply equally to constituents of food 
that may have a common mechanism of action with the pesticidal 
substances that are the subject of this exemption (59 FR 60535). 
Variation in the levels of these substances are not likely to result in 
overall significantly different dietary exposures. As noted in the 
proposal (59 FR at 60538) ``plant varieties that meet the sexually 
compatible standard produce food that is safe for human consumption 
and/or appropriate processing procedures are widely known and routinely 
used by consumers in preparation of food from such sources.'' However, 
should EPA in the future identify substances with a common mechanism of 
toxicity with the plant-pesticides that are the subject of the proposed 
exemption, both FIFRA and FFDCA give the Agency adequate authority to 
take appropriate action to address any risks to humans health.
    EPA is not aware of any other substances outside of the food supply 
that may have a common mechanism of toxicity with the residues of the 
pesticidal substances that are the subject of the proposed exemption 
(59 FR 60535), although it cannot rule out the possibility. Should EPA 
in the future identify substances with a common mechanism of toxicity 
other than those found in the parts of plants used as food, both FIFRA 
and FFDCA give the Agency adequate authority to take appropriate action 
to address any risks to humans health.
    Because EPA already considered the safety of food containing 
residues of pesticidal substances derived from sexually compatible 
plants and other constituents of food that may share a common mechanism 
of toxicity with those residues when it issued the proposal (FR 60535), 
it is not requesting additional comment on that topic. Comments are 
requested only on the new issue of whether there are any substances 
outside of the food supply that have a common mechanism of toxicity 
with the residues of the pesticidal substances that are the subject of 
the proposed exemption, and the effects of any such substances on human 
health.
    6. Aggregate exposures of consumers including non-occupational 
exposures. EPA considered the available information on the aggregate 
exposure level of consumers to pesticidal substances in the plant-
pesticides to be exempt in the 1994 FFDCA and FIFRA proposals (59 FR 
60519 and 60535). This included a consideration of exposures from 
dietary sources (59 FR 60535) as well as from other non-occupational 
sources (59 FR 60519). As indicated in EPA's policy statement, ``plant-
pesticides are likely to present a limited exposure of the pesticidal 
substance to humans. In most cases, the predominant, if not the only, 
exposure route will be dietary. Significant respiratory and dermal 
exposures will be unlikely'' (59 FR at 60513). As explained in the 
FFDCA and FIFRA proposals and the EPA's policy statement (59 FR 60494) 
and associated dockets, plant-pesticides present negligible exposure of 
pesticidal substances to humans outside of the dietary route because 
the substances are in the plant tissue and thus are found either within 
the plant or in close proximity to the plant. EPA considered dietary 
exposure to the pesticidal substances in the proposed FFDCA exemption 
(59 FR 60535) and summarized its evaluation in Unit IV.A. of this 
supplemental notice.
    Despite EPA's belief that, because of the nature of plant-
pesticides, there is little likelihood of exposure other than through 
the dietary route, EPA in this supplemental notice sets forth in 
greater detail its considerations concerning other exposure routes. 
With regard to the dermal route of exposure, the pesticidal substances 
that are the subject of the proposed exemption (59 FR 60535) 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. However, on a per person basis, the potential 
amounts involved in these exposures are negligible in comparison to 
potential exposure through the dietary route. Moreover, substances that 
occur naturally in food, including the pesticidal substances that are 
the subject of the proposed exemption, are unlikely to cross the 
barrier provided by the skin and thus the responses seen on rare 
occasions to substances in food are most likely to be localized skin 
irritations. Whether these irritations are caused by the pesticidal 
substance component of plant-pesticides is unknown but given the 
thousands of constituents of any food of plant origin, the probability 
that substances other than the plant-pesticides are the irritants is 
very high. Because substances present in food are unlikely to pass 
through the skin, dermal exposures are not additive to dietary 
exposures.
    With regard to exposure through inhalation, the pesticidal 
substances may in some cases be present in pollen and some individuals 
(those near enough to farms, nurseries or other plant-growing areas to 
be exposed to wind-blown pollen) may be exposed, through inhalation, to 
the pollen. On a per person basis, the potential amounts of pollen 
involved in these exposures are negligible in comparison to potential 
exposure through the dietary route. Moreover, it is unlikely that 
exposure to the pollen is equivalent to exposure to the pesticidal 
substance. The pesticidal substance will not in every case be present 
in the pollen. When it is present in pollen, the pesticidal substance 
will be integrated into the tissue of the pollen grain. EPA cannot rule 
out the possibility that in some cases, the pesticidal substance or 
some piece of the pesticidal substance might be bound to the surface of 
the pollen grain (as opposed to the more likely circumstance of the 
substance being within the pollen grain). If the substance is bound to 
the surface of the pollen, lung or respiratory tract tissue in humans 
might be exposed to the pesticidal substance. Substances that occur 
naturally in pollen, including the pesticidal substances that are the 
subject of the proposed exemption, are unlikely to cross the barrier 
provided by the mucous membrane of the respiratory tract and thus are 
not additive to dietary exposure.
    EPA also evaluated potential non-occupational exposures in drinking 
water. As noted in the preceding paragraphs, the substances in plants 
or parts of plants, including the pesticidal substances that are the 
subject of the proposed exemption (59 FR 60535), are produced inside 
the plant itself. The pesticidal substances are integrated into and an 
integral part of the living tissue of the plant. When the plant dies or 
a part is removed from the plant,

[[Page 27139]]

microorganisms colonizing the tissue immediately begin to digest it, 
using the components of the tissue (including any pesticidal substances 
in the tissue) as building blocks for making their own tissues or for 
fueling their own metabolisms. The pesticidal substances that EPA 
proposed to exempt are subject to the same processes of degradation and 
decay that all organic matter undergoes. This turnover of biochemical 
materials in nature through a process of degradation occurs fairly 
rapidly. Therefore, these pesticidal substances do not persist in the 
environment or bioaccumulate. There is no indication that naturally 
occurring plant biochemical compounds, including the pesticidal 
substances that are the subject of the proposed exemption, are 
resistant to this degradation. Because of the fairly rapid turnover of 
these substances, 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 from surface water sources. 
Should they resist degradation long enough to enter groundwater, they 
are unlikely to present anything other than a negligible exposure in 
drinking water drawn from groundwater. Therefore, although a potential 
for non-dietary exposure (i.e., non-food oral, dermal and inhalation) 
in non-occupational settings may exist, EPA expects such exposure to be 
negligible.
    With regard to exposure to ``other related substances,'' EPA is not 
aware of any other substances that may be related, via a common 
mechanism of toxicity, to the pesticidal substances that are the 
subject of the proposed exemption (59 FR 60535), other than related 
substances that are present in parts of plants used as food. Thousands 
of substances are present in the edible parts of plants. These may 
include substances related, via a common mechanism of toxicity, to the 
pesticidal substances that are the subject of the proposed exemption. 
These related substances have long been accepted as part of the human 
diet. Extensive use and experience show the safety of foods containing 
these substances. It also shows the safety of these substances consumed 
in aggregate through the dietary route with the pesticidal substances 
that are the subject of the proposed exemption. With regard to non-
occupational exposure through routes other than dietary exposure, no 
evidence, in the many years of human experience with the growing and 
consumption of food from plants that may contain substances that may be 
related via a common mechanism of toxicity to the pesticidal substances 
that are the subject of the proposed exemption, indicates that adverse 
effects due to aggregate exposure through the dietary, non-food oral, 
dermal and inhalation routes occurs.
    Should EPA in the future identify substances related via a common 
mechanism of toxicity to the pesticidal substances that are the subject 
of the proposed exemption, FIFRA and the FFDCA provide the Agency 
adequate authority to take appropriate action to address any risks 
associated with those related substances. Substances that are isolated 
from the plant's tissues, concentrated and then applied topically as 
pesticides to the plant or to food would not be covered by the proposed 
exemption (59 FR 60535), but would be subject to the tolerance 
requirements of FFDCA.
    Because the Agency already considered exposure to the pesticidal 
substances that are the subject of the proposed exemption (59 FR 60535) 
and to substances related via a common mechanism of toxicity to these 
pesticidal substances in food when it issued the proposal, it is not 
requesting additional comment on this topic. Comments are requested 
only on the issue of whether there are additional substances outside 
that food supply that are related, via a common mechanism of toxicity, 
to residues of the pesticidal substances that are the subject of the 
proposed exemption and the effects of exposure to any such substances 
on human health.
    7. Sensitivities of subgroups. In 1994, EPA considered available 
information on the sensitivities of subgroups as it pertains to the 
pesticidal substances derived from sexually compatible plants in the 
proposal (59 FR 60535) and has summarized the evaluation in Unit IV.A. 
of this supplemental notice.
    8. Naturally occurring estrogen or other endocrine effects. FFDCA 
now directs EPA, in establishing an exemption from the requirement of a 
tolerance, to consider ``such information as the Administrator may 
require on whether the pesticide chemical may have an effect in humans 
that is similar to an effect of a naturally occurring estrogen or other 
endocrine effect'' (21 U.S.C. 346(a)(q)). Congress allowed EPA 2 years 
to establish a screening program to determine whether certain pesticide 
chemicals may have estrogenic effects and an additional year to 
implement the program (21 U.S.C. 408(p)). As part of the screening and 
implementation process, EPA is determining what information might be 
required and how it will address estrogenic effects from pesticide 
residues in general.
    While there is some information on estrogenic effects from exposure 
to certain pesticides, the data are limited. It is known that certain 
food plants contain estrogen mimics, termed phytoestrogens. Such 
phytoestrogens are currently being consumed by humans in food derived 
from plants. EPA cannot rule out the possibility that such 
phytoestrogens could be used as plant-pesticides. Potential exposure of 
humans via consumption of plant tissue to phytoestrogens exerting 
estrogenic effects and used as plant-pesticides may need to be 
considered when the issue of endocrine disruptors is examined by EPA. 
If dietary exposure to phytoestrogens (that are also plant-pesticides) 
is discovered to be a significant factor, the Agency will re-examine 
this proposed exemption from the requirement of a tolerance (59 FR 
60535) in light of that information.
    9. Safety factors. In the 1994 proposal, EPA did not rely on the 
available animal data in reaching its determination that a tolerance is 
not necessary to protect the public from pesticidal substances derived 
from sexually compatible plants (59 FR 60535). As discussed in Unit 
IV.A. of this supplemental notice, EPA relied on the long history of 
safe human consumption of the pesticidal substances that are the 
subject of the proposed exemption in food from sexually compatible 
plant populations and in food derived from animals that consume forage 
and other crops (e.g., corn and other grains). EPA continues to believe 
that long-term evidence of human consumption, not animal 
experimentation data, is the appropriate information base for the 
proposed exemption (59 FR 60535). Because EPA did not rely on animal 
experimentation data, the Agency did not consider which safety factors 
would be appropriate to use in assessing risk to humans based on data 
generated through experiments on animals.
    10. Infants and children.--a. Dietary consumption patterns. In the 
1994 proposal (59 FR 60535), EPA considered available information on 
the dietary consumption pattern of infants and children as pertains to 
the pesticidal substances derived from sexually compatible plants and 
has summarized the evaluation in Unit IV.A. of this supplemental 
notice. 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 soy based products. Infants begin as early as 4-months of age to 
consume

[[Page 27140]]

specific types of solid foods containing residues of pesticidal 
substances that are the subject of the proposed exemption. Subsequent 
to 4 months of age, apart from processing to facilitate swallowing, the 
diets of infants are 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.
    b. Special susceptibility. In the 1994 proposal (59 FR 60535), EPA 
considered available information on the potential for susceptibility of 
infants and children, including pre- and post-natal toxicity, as these 
factors pertain to the pesticidal substances derived from sexually 
compatible plants and has summarized the evaluation in Unit IV.A. of 
this supplemental notice.
    c. Cumulative effects of residues with other substances with a 
common mechanism of toxicity. In the 1994 proposal (59 FR 60535), EPA 
examined the available information on the cumulative effect of residues 
of pesticidal substances derived from sexually compatible plants as 
well as other substances in food that may have a common mechanism of 
toxicity. The Agency's consideration in the proposal of the effects of 
the residues of pesticidal substances that are the subject of the 
proposed exemption (59 FR 60535) for the general population also 
included consideration of effects for infants and children. See Unit 
IV.B.5. of this supplemental notice for a discussion of cumulative 
effects of the pesticide chemical residues and other substances that 
have a common mechanism of toxicity.
    Because EPA already considered the safety of food containing 
residues of pesticidal substances derived from sexually compatible 
plants and other constituents of food when it issued the proposal (FR 
60535), the Agency is not requesting additional comment on that topic. 
Comments are requested only on the new issue of whether there are any 
substances outside of the food supply with a common mechanism of 
toxicity to the residues of the pesticidal substances that are the 
subject of the proposed exemption and the effects of any such 
substances on infants and children.
    d. Margin of safety. In determining whether the residues of the 
pesticidal substances that are the subject of the proposed exemption 
(59 FR 60535) are safe, FFDCA section 408(b)(2)(C) directs EPA to apply 
a tenfold margin of safety for the residues and other sources of 
exposure to infants and children to account for potential pre- and 
post-natal toxicity and completeness of data on threshold effects with 
respect to exposure and toxicity to infants and children, unless a 
different margin will be safe. In proposing the exemption, EPA based 
its assessment of exposure and toxicity upon reliable information (Ref. 
1) including the long history of safe human consumption of food 
containing residues of the pesticidal substances that are the subject 
of the proposed exemption and other substances in food that may have a 
common mechanism of toxicity, and the unique nature of plant-
pesticides. EPA did not rely on animal data. EPA relied on observations 
concerning whole food consumption by humans and did not rely on single 
entity testing, wherein substances are isolated from a plant source, 
and fed to animals at high concentrations (Ref. 1). EPA relied on the 
vast experiential base of actual food consumption patterns rather than 
limited testing situations. EPA thus, did not utilize animal or other 
studies that would yield data that could be subjected to an additional 
margin of safety. (See Units IV.A. and IV.B.3. of this supplemental 
notice). As a result, the FQPA amendments to FFDCA do not affect EPA's 
analysis.

C. Safety Determinations in Light of FFDCA Amendment

    Based on the information discussed in the 1994 proposals (59 FR 
60496 through 60547), the discussion in Unit IV.A. and the analysis in 
Unit IV.B. of this supplemental notice, EPA concludes that there is a 
reasonable certainty that no harm will result to the U.S. population in 
general, and U.S. infants and children, from aggregate exposure to 
residues of pesticidal substances derived from sexually compatible 
plants, including all anticipated dietary exposures and all other 
exposures for which there is reliable information. Under the proposed 
exemption from the requirement for a tolerance (59 FR 60535), EPA would 
exempt residues of pesticidal substances that are normally components 
of (not new to) food from plants in sexually compatible populations. 
Extensive use and experience show the safety of foods containing these 
substances. No evidence, in the many years of human experience with the 
growing and consumption of food from plants containing the pesticidal 
substances that are the subject of the proposed exemption (59 FR 
60535), indicates that adverse effects due to aggregate exposure 
through the dietary, non-food oral, dermal and inhalation routes occur.
    The conclusion that residues of pesticidal substances derived from 
sexually compatible plants should be exempt from tolerance requirements 
under the FFDCA section 408 safety standard also lends support to EPA's 
proposed FIFRA exemption (59 FR 60519) for plant-pesticides derived 
from sexually compatible plants with respect to human dietary risks. In 
the FIFRA proposal, EPA utilized two criteria to determine whether 
plant-pesticides should be exempt: (1) Whether they posed a low 
probability of risk, and (2) whether they caused unreasonable adverse 
effects on the environment. Based upon the determination that residues 
of pesticidal substances subject to the proposed exemption (59 FR 
60535) and the nucleic acid component of plant-pesticides (59 FR 60542) 
meet the FFDCA section 408 safety test, EPA concludes plant-pesticides 
derived from sexually compatible plants would pose only a low 
probability of human dietary risk and also would not pose an 
unreasonable adverse effect with respect to such risks.

D. Other Considerations

    When the Agency proposed to establish an exemption from the 
requirement of a tolerance for residues of pesticidal substances 
derived from sexually compatible plants (59 FR 60535), EPA did not 
propose any numerical limitation on the amount of pesticidal substance 
that could be present in food containing these residues. EPA consulted 
in 1994 with the Department of Health and Human Services (DHHS) in 
developing the proposed exemption (59 FR 60535) and this supplemental 
notice and will consult with the Secretary of HHS prior to issuing the 
final rule. Because the 1994 proposal was for the exemption from the 
requirement of a tolerance, the Agency has concluded that an analytical 
method for detecting and measuring the levels of the residues of the 
subject pesticidal substances in or on food is not required.

V. Comments

A. Confidential Business Information

    Information submitted as comments concerning this supplemental 
notice may be claimed confidential by marking any part or all of that 
information as ``Confidential Business Information'' (CBI). CBI should 
not be submitted through e-mail. Information marked as CBI will not be 
disclosed except in accordance with procedures set forth in

[[Page 27141]]

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.

B. 30-Day Comment Period

    EPA is allowing a 30-day comment period because it has determined 
that such a period will provide the public with an adequate opportunity 
to respond to the additional issues raised in this supplemental notice. 
FFDCA and FIFRA do not specify a comment period for this type of 
notice. EPA has decided that a 30-day comment period is reasonable 
because this supplemental notice raises very few new issues that were 
not already available for public comment. As discussed in Unit IV. of 
this supplemental notice, EPA effectively considered most of the 
factors required by the FQPA amendments of FFDCA and FIFRA relevant to 
the proposed exemptions when it issued the proposed package of notices 
describing EPA's approach in 1994 (59 FR 60496, 60519, 60535, 60542 and 
60545). At that time, the public had an opportunity to review both the 
Agency's rationale for the proposals and the underlying support 
documents during a 90-day public comment period. Only a limited number 
of new issues have been raised by the FQPA amendments to FFDCA and 
FIFRA and the Agency continues to rely upon the information already in 
the docket for the 1994 proposals and thus 30 days should provide 
adequate time for public comment. In addition, EPA believes that it is 
in the interest of the public to publish the final exemption from the 
requirement of a tolerance in a timely manner.

C. Request for Comments

    Interested persons are invited to submit written comments on the 
new issues raised in this supplemental notice specifically on:
    (1) Whether there are substances, outside of the food supply, 
sharing a common mechanism of toxicity with pesticidal substances that 
are derived from sexually compatible plants. Commenters are asked to 
submit information on the cumulative effects of such substances and the 
pesticidal substances that are the subject of the proposed exemption 
(59 FR 60535).
    (2) Whether there are substances, outside of the food supply, 
related via a common mechanism of toxicity to pesticidal substances 
that are derived from sexually compatible plants, to which humans might 
be exposed through non-occupational routes of exposure. Commenters are 
asked to describe routes through which such exposure might occur, 
including exposure to major identifiable subgroups of human populations 
(e.g., infants and children). If such routes are identified, commenters 
are requested to provide information on the nature and levels of the 
expected exposure.
    Entities may also offer comments on issues V.C.1. and V.C.2. above 
as they apply to Option 2 as described in the November 23, 1994 Federal 
Register (59 FR at 60537) ``Plant-pesticides derived from plants within 
the same genus or from sexually compatible plants'' under the revised 
FFDCA section 408 safety standard. The Agency will not consider 
comments that address issues or information already presented for 
public comment in the proposed rule issued in the November 23, 1994, 
Federal Register.
    Commenters who possess information on substances occurring in food 
that may have estrogenic effects and may be used as plant-pesticides 
are requested to send such information to EPA.
    In this supplemental notice, EPA describes in greater detail the 
rationale supporting the statement made in the 1994 Federal Register 
(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 official comment 
period. Commenters may comment on this more detailed rationale.
    In this supplemental notice, EPA also describes in greater detail 
how the rationale presented in the 1994 Federal Register (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. No comments were received on this statement during the 
official comment period. Commenters may comment on this more detailed 
rationale specifically addressing infants and children as part of the 
larger human population.

VI. Public Docket

    The official record for this rulemaking, as well as the public 
version, has been established for this rulemaking under docket control 
number ``OPP-300368A'' (including comments and data submitted 
electronically as described below). A public version of this record, 
including printed, paper versions of electronic comments, which does 
not include any information claimed as CBI, is available for inspection 
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal 
holidays. The official rulemaking record is located at the address in 
``ADDRESSES'' at the beginning of this document.
    Electronic comments can be sent directly to EPA at:

    [email protected]
    Electronic comments must be submitted as an ASCII file avoiding the 
use of special characters and any form of encryption. Comment and data 
will also be accepted on disks in Wordperfect 5.1 file format or ASCII 
file format. All comments and data in electronic form must be 
identified by the docket control number ``OPP-300368A.'' Electronic 
comments on this supplemental notice may be filed online at many 
Federal Depository Libraries.

VII. 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.

VIII. Regulatory Assessment Requirements

    This supplemental notice merely seeks additional comments on the 
proposed rules with regard to the potential impact that the new 
statutory amendments imposed by the August 3, 1996 Food Quality 
Protection Act (FQPA) might have on the provisions as proposed. As 
such, this notice does not contain any new proposed requirements that 
would require additional consideration by the Office of Management and 
Budget (OMB) under Executive Order 12866, entitled Regulatory Planning 
and Review (58 FR 51735, October 4, 1993) or the Paperwork Reduction 
Act (PRA), 44 U.S.C. 3501 et seq. It does not require any other action 
under Executive Order 12875, entitled Enhancing the Intergovernmental 
Partnership (58 FR 58093, October 28, 1993), Executive Order 12898, 
entitled Federal Actions to Address Environmental Justice in Minority 
Populations and Low-Income Populations (59 FR 7629, February 16, 1994), 
or the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et seq.). The 
Agency's activities related to these regulatory assessment requirements 
are discussed in the proposed rules.
    EPA did not consider Title II of the Unfunded Mandates Reform Act 
of 1995 (UMRA) (Pub. L. 104-4) at the proposal stage because the 
proposed rules were

[[Page 27142]]

issued prior to its enactment. Although this supplemental notice is not 
subject to UMRA because it neither proposes or finalizes any regulatory 
requirements, the applicability of the UMRA requirements will be 
addressed in the final rules.

List of Subjects in 40 CFR Part 180

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

    Dated: May 7, 1997.
Lynn R. Goldman
Assistant Administrator for Prevention, Pesticides and Toxic 
Substances.

[FR Doc. 97-12784 Filed 5-15-97; 8:45 am]
BILLING CODE 6560-50-F