[Federal Register Volume 62, Number 95 (Friday, May 16, 1997)]
[Proposed Rules]
[Pages 27149-27155]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-12785]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300367A; FRL-5716-6]
RIN 2070-AC02
Plant-Pesticides; Viral Coat Proteins; Supplemental Notice of
Proposed Rulemaking
AGENCY: Environmental Protection Agency (EPA).
ACTION: Supplemental notice of proposed rulemaking.
-----------------------------------------------------------------------
SUMMARY: This document announces the availability of information for
additional public comment regarding the proposed exemption from the
requirement of a tolerance under the Federal Food, Drug, and Cosmetic
Act (FFDCA) for residues of coat proteins from plant viruses when these
coat proteins are produced and used as plant-pesticides in plants or
plant parts used as raw agricultural commodities. 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 viral coat
proteins produced in plants as part of a plant-pesticide 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 viral coat proteins produced in plants as part of a
plant-pesticide. EPA believes that it considered most of the
substantive issues associated with the FQPA amendments when it issued
the proposal 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 that proposal.
DATES: Comments, identified by the docket number ``OPP-300367A,'' 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 VI. of this document. No Confidential
Business Information (CBI) should be submitted through e-mail.
FOR FURTHER INFORMATION CONTACT: 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:
[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
documents. The notices 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). Viral coat proteins produced in plants for viral coat
protein mediated viral resistance are considered plant-pesticides
because of their intended role in plant resistance to viral infection.
One of the five notices (59 FR 60545) proposed to exempt viral coat
proteins produced in plants as part of a plant-pesticide, or segments
of coat proteins, 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 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 viral coat proteins produced in plants as part of a plant-
pesticide. For pesticidal substances in this category, many years of
human experience with consumption of food containing plant viruses
suggest that these pesticidal substances present negligible risk.
Specifically, EPA proposed that ``residues of coat proteins from plant
viruses, or segments of the coat proteins, produced in living plants as
plant-pesticides are exempt from the requirement of a tolerance'' (59
FR at 60547).
This supplemental notice addresses the coat protein portion of the
plant-pesticide 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 this supplemental notice may
also affect EPA's final determination on a proposed exemption under
FIFRA (59 FR at 60535) for plant-pesticides that are coat proteins from
plant viruses.
EPA is publishing this supplemental notice 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 a tolerance for
residues of viral coat proteins produced in plants as part of a plant-
pesticide. 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 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
[[Page 27150]]
relative to the proposed exemption (59 FR 60545) 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 residues of
viral coat proteins produced in plants as part of a plant-pesticide,
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 mechanism of toxicity (21 U.S.C. 346a(b)(2)(C) and (c)(2)(B)).
III. Summary of Proposed Rule
In the November 23, 1994 Federal Register, EPA proposed to exempt
from
[[Page 27151]]
the requirement of a tolerance coat proteins from plant viruses, or
segments of such proteins when these proteins, or segments of these
proteins, are produced in plants for the purpose of protecting plants
against viral disease. Coat proteins are those substances that viruses
produce to encapsulate and protect their genetic material. When the
genetic material encoding the coat protein is introduced into a plant's
genome, the plant is able to resist infections by the virus donating
the genetic material for the coat protein (as well as infections by
virus strains closely related to the donor virus). This resistance is
termed viral coat protein mediated resistance or vcp-mediated
resistance.
IV. Risk Assessment and Safety Determinations
A. Risk Assessment in Proposal
EPA's rationale for its 1994 proposal for an exemption from the
requirement of a tolerance for viral coat proteins was based on the
following points: (1) Virus-infected plants have always been a part of
the human and domestic animal food supply since most crops are
frequently infected with plant viruses and food from these crops have
been and are being consumed without detectable adverse human health
effects. (2) Plant viruses have never been shown to be infectious to
humans, including children and infants, or mammals. Plant viruses are
not able to replicate in mammals or other vertebrates, limiting the
possibility of human infection. In addition, this exemption applies
only to the portion of the viral genome coding for the whole coat
protein or a segment of the coat protein which will be expressed in the
plant. The coat protein or a segment of the coat protein by itself is
incapable of forming infectious particles. Since whole, intact plant
viruses are not known to cause deleterious human health effects, it is
reasonable to assume that a subunit of these viruses likewise will not
cause adverse human health effects when consumed at rates currently
found in the food supply.
In developing its regulatory approach for plant-pesticides, EPA
requested the advice of a subpanel, composed of experts in the relevant
scientific disciplines, of the FIFRA Scientific Advisory Panel (SAP).
On December 18, 1992, the SAP subpanel was convened to review a draft
policy statement for plant-pesticides and respond to a series of
scientific questions posed by the Agency. One question that the Agency
asked the SAP subpanel was whether coat proteins from plant viruses
might present a dietary risk. In answer to the question, the subpanel
stated that ``[s]ince viruses are ubiquitous in the agricultural
environment at levels higher than will be present in transgenic plants,
and there has been a long history of `contamination' of the food supply
by virus coat protein, there is [a] scientific rationale for exempting
transgenic plants expressing virus coat protein from the requirement of
a tolerance.''
As described in the proposed regulation (59 FR 60545), entire
infectious particles of the plant viruses, including the coat protein
component, have been and are being consumed by humans with no observed
adverse effects. Virus-infected food plants have always been a part of
the human and domestic animal food supply (Refs. 1, 2, 3, and 4). For
example, at the beginning of this century virtually every commercial
cultivar of potatoes grown in the United States and Europe was infected
with either one or some complex of potato viruses (Ref. 1).
All plants have viruses that can infect them. While some viruses
may be limited to certain tissues (e.g., the vascular system) or organs
(e.g., roots), most plant viruses are found throughout the various
organs and tissues of plants. Viruses, including the coat protein
component, are found in the fruit, leaves, and stems of most plants.
The long history of inadvertent mammalian consumption of the entire
plant virus particle in foods with no observed ill effects presents a
strong argument to support the human and domestic animal safety of the
entire virus in foods. Concentrations of the virus particles in
infected plants vary widely according to the host plant, length of
infection, and the reproductive life cycle of the virus itself. In
general, EPA anticipates that the amounts of viral coat protein
consumed in the diet due to the production of viral coat proteins in
vcp-mediated resistance will be similar to the amounts of viral coat
proteins currently consumed.
Plant pathogenic viruses have never been shown capable of infecting
or replicating in vertebrates (Refs. 1, 2, and 5). Intact, infectious,
whole plant viruses, therefore, are not infectious to humans, including
children and infants. Given that the complete virus is not infectious
to vertebrates, it is reasonable to assume that a noninfectious
subcomponent (i.e., a coat protein or a segment of a coat protein) of
the virus would not be hazardous to humans or animals.
B. Risk Assessment in Light of Amendment to FFDCA
After EPA issued its proposed exemption from the requirement of a
tolerance for viral coat proteins produced in plants as part of a
plant-pesticide (59 FR 60545), 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 viral coat proteins produced in
plants as part of a plant-pesticide, or segments of such proteins, 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 viral coat proteins, or
segments of such proteins, produced in plants as part of a plant-
pesticide 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.
This 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
viral coat proteins produced in plants as plant-pesticides.
1. Available data. EPA considered in 1994, the validity,
completeness and reliability of the available data with regard to coat
proteins from plant viruses in the proposals (59 FR 60519 and 60545)
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 viral coat proteins produced in plants as part
of a plant-pesticide in the proposals (59 FR 60519 and 60545) and has
summarized its evaluation in Unit IV.A. of this supplemental notice.
[[Page 27152]]
3. Relationship of studies to humans. EPA in 1994 considered the
available information concerning the relationship to humans of toxic
effects of viral coat proteins produced in plants as part of a plant-
pesticide when it issued the proposals (59 FR 60519 and 60545) 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. Because knowledge of human
consumption of food from virus infected crop plants (as well as meat
and milk products derived from animals eating such plants) was
available and adequately addressed the issues of hazard and exposure,
the Agency did not use, for the proposed exemption (59 FR 60545), data
generated in the laboratory through animal testing.
4. Dietary consumption patterns. EPA considered in the 1994
proposal the available information on the varying dietary consumption
patterns of major identifiable consumer subgroups as it pertains to
consumption of food from virus infected 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. EPA has examined the available information on
the cumulative effect of consuming virus infected plants and other
substances in plants that may have a common mechanism of human
toxicity. EPA summarizes this information and its analysis in Unit
IV.A. of this supplemental notice.
Viral coat proteins are nontoxic proteins widespread in food. They
have not been associated with toxic or pathogenic effects to animals or
humans. Because viral coat proteins in foods have no known human
toxicity, no cumulative effects can be identified for viral coat
proteins produced in plants as part of a plant-pesticide. FQPA also
directs the Agency to examine whether there are other substances that
have a common mechanism of toxicity with residues of viral coat
proteins produced in plants as part of a plant-pesticide. Based on
available information which indicates that viral coat proteins in food
have no human toxicity, EPA is not aware of any other substances that
might have a common mechanism of human toxicity with residues of viral
coat proteins produced in plants as part of a plant-pesticide.
Experience with residues of viral coat proteins in the current food
supply gives no indication of human or animal toxicity. If information
becomes available that indicates this finding is not appropriate, EPA
will consider the validity of the new information and act to amend this
tolerance exemption as needed.
EPA is not aware of any substances outside of the food supply that
may have a common mechanism of toxicity with residues of viral coat
proteins produced in plants as part of a plant-pesticide since viral
coat proteins are not toxic to humans or animals.
EPA considered the safety of foods containing residues of viral
coat proteins when it issued the proposal and is not requesting
additional comment on that topic. Comments are only requested on EPA's
conclusion that there are no substances outside of the food supply that
may have a cumulative toxic effect with residues of viral coat proteins
produced in plants as part of a plant-pesticide.
6. Aggregate exposures including non-occupational exposures. EPA
has considered the available information on the aggregate exposure
level of consumers to viral coat proteins produced in plants as part of
a plant-pesticide in the 1994 FFDCA and FIFRA proposals (59 FR 60519
and 60545). This included a consideration of exposures from dietary
sources (59 FR 60545) 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 EPA's policy statement (59 FR 60496) 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 residues of viral coat proteins produced in plants as part
of a plant-pesticide in the proposed FFDCA exemption (59 FR 60545) and
summarized its evaluation in Unit IV.A. of this supplemental notice.
Despite EPA's belief that, because of the nature of viral coat
proteins produced in plants as part of a plant-pesticide, 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, viral coat proteins produced in plants as
part of a plant-pesticide 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
viral coat proteins produced in plants as part of a plant-pesticide,
are unlikely to cross the barrier provided by the skin.
With regard to exposure through inhalation, viral coat proteins
produced in plants as part of a plant-pesticide 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. It is unlikely that exposure to the pollen is
equivalent to exposure to viral coat proteins produced in plants as
part of a plant-pesticide. When present in pollen, the viral coat
proteins produced in plants as part of plant-pesticides will likely be
integrated into the tissue of the pollen grain and not likely to be
bound to the surface of the pollen grain. Pollen grains and the
substances that occur naturally in pollen are unlikely to cross the
barrier provided by the mucous membrane of the respiratory tract and
thus are not additive to dietary exposure. Some viruses are transmitted
by wind-borne vectors, i.e., pollen or fungal spores and individuals
near enough to farms, nurseries or other plant-growing areas to be
exposed to these wind-blown vectors may be exposed, through inhalation,
to the whole virus particle. Since no evidence suggests that exposure
to whole plant viruses borne by wind-blown pollen or fungal spores
results in adverse effects, it is unlikely that exposure to pollen that
may contain viral coat proteins produced in plants as part of a plant-
[[Page 27153]]
pesticide would result in adverse effects.
EPA also evaluated potential non-occupational exposures in drinking
water. As noted in the preceding paragraphs, most substances in plants
or parts of plants, including viral coat proteins produced in plants as
part of a plant-pesticide, are found only inside the plant itself.
Viral coat proteins produced in plants as part of a plant-pesticide are
an integral part of the living tissue of the plant. When the plant dies
or a part is removed from the plant, microorganisms colonizing the
tissue immediately begin to digest it, using the components of the
tissue (including viral coat proteins produced in plants as part of a
plant-pesticide) as building blocks for making their own tissues or for
fueling their own metabolisms. Viral coat proteins, or segments of
these proteins, produced in plants as part of a plant-pesticide 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,
viral coat proteins produced in plants as part of a plant-pesticide do
not persist in the environment or bioaccumulate. There is no indication
that naturally occurring plant biochemical compounds, including viral
coat proteins produced in plants as part of plant-pesticides, are
particularly resistant to this degradation. Because of the rapid
turnover of these substances, even if they reach surface waters, they
are unlikely to present anything other than a very negligible exposure
in drinking water drawn from either surface or ground water sources.
Therefore, the potential for non-dietary exposure (i.e., non-food oral,
dermal and inhalation) in non-occupational settings is limited and EPA
expects such exposure to be negligible.
With regard to exposure to ``other related substances,'' EPA is not
aware of any other substances either in food or outside the food supply
that may be related, via a common mechanism of toxicity, to viral coat
proteins produced in plants as part of a plant-pesticide since viral
coat proteins are not toxic to humans or animals. With regard to non-
occupational exposure through routes other than dietary exposure, since
viral coat proteins are not toxic, EPA is not aware of substances
outside the food supply that may be related via a common mechanism of
toxicity to the viral coat proteins produced in plants as part of a
plant-pesticide. No evidence indicates that adverse effects due to
aggregate exposure of viral coat proteins with such substances through
the dietary, non-food oral, dermal and inhalation routes occurs.
EPA considered exposure to residues of viral coat proteins produced
in plants as part of a plant-pesticide when it issued the proposal and
is not requesting additional comment on that topic. Comments are only
requested on EPA's conclusion that there are no substances outside of
the food supply that are related, via a common mechanism of action, to
residues of viral coat proteins produced in plants as part of a plant-
pesticide for which EPA must consider exposure in aggregate with viral
coat proteins.
7. Sensitivities of subgroups. In 1994, EPA considered available
information on the sensitivities of subgroups as it pertains to viral
coat proteins produced in plants as part of a plant-pesticide in the
proposal (59 FR 60545). The Agency's evaluation is summarized 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.
There is some information on estrogenic effects by exposure to
pesticides but the data are limited and do not pertain to viral coat
proteins. Based on available information concerning the presence of
viruses in the food supply with no detectable adverse human health
effects, EPA does not expect viral coat proteins expressed in plants as
part of a plant-pesticide to cause estrogen or other endocrine effects.
If EPA becomes aware of a potential for estrogenic or endocrine effect
from exposure to viral coat proteins produced in plants as part of a
plant-pesticide, EPA will reexamine this tolerance exemption 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 viral coat proteins produced
in plants as part of a plant-pesticide (59 FR 60545). As discussed in
Unit IV.A. of this supplemental notice, EPA relied on the long history
of safe human consumption of food containing plant viruses and
consumption of food derived from animals that consume forage and other
crops (e.g., corn and other grains) that are also likely to contain
plant viruses. 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 60545). 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 60545), EPA considered available information on
the dietary consumption pattern of infants and children as it pertains
to viral coat proteins in food 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 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. Since plant viruses are ubiquitous in
plant foods, EPA concluded that infants and children are exposed as
part of a normal diet to viral coat proteins. There is no evidence that
such exposure leads to any harm.
b. Special susceptibility. In the 1994 proposal (59 FR 60545), EPA
considered available information on the potential for susceptibility of
infants and children, including pre- and post-natal toxicity, as these
factors pertain to viral coat proteins produced in plants as part of a
plant-pesticide. There is no scientific evidence that viral coat
proteins as a component of food would have a different effect on
children than
[[Page 27154]]
they would on the adult population. EPA summarizes its analysis of the
effect of consumption in food of viral coat proteins on human health 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 60545), EPA
examined the available information on the cumulative effect of residues
of viral coat proteins produced in plants as part of a plant-pesticide
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 viral coat proteins produced in plants as part of a
plant-pesticide on 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 viral
coat proteins and other substances that have a common mechanism of
toxicity.
EPA considered the safety of foods containing residues of viral
coat proteins when it issued the proposal and it is not requesting
additional comment on that topic. Comments are only requested on EPA's
conclusion that there are no substances outside of the food supply that
may have a cumulative toxic effect with residues of viral coat proteins
produced in plants as part of a plant-pesticide.
d. Margin of safety. In determining whether the residues of viral
coat proteins produced in plants as part of a plant-pesticide 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 including the long history of
safe human consumption of food containing residues of viral coat
proteins produced in plants as part of a plant-pesticide and other
substances in food, 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 animals are exposed to high concentrations of substances
isolated from a plant source. EPA relied on the vast base of the human
experience with actual food consumption rather than limited testing
situations involving exposure to high concentrations of viral coat
proteins. 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 viral coat proteins produced in plants as part of a plant-
pesticide, 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 60545), EPA would
exempt residues of viral coat proteins produced in plants as part of a
plant-pesticide. 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 viral coat proteins, indicates that adverse effects due to
aggregate exposure through the dietary, non-food oral, dermal and
inhalation routes occur.
The conclusion that residues of viral coat proteins produced in
plants as part of a plant-pesticide should be exempt from tolerance
requirements under the FFDCA section 408 safety standard also lends
support to one of EPA's proposed FIFRA exemptions (59 FR 60519) with
respect to human dietary risks: plant-pesticides that are coat proteins
from plant viruses (59 FR at 60535). 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 viral coat proteins (59
FR 60545) and the nucleic acid component of a plant-pesticide (59 FR
60542) meet the FFDCA section 408 safety test, EPA concludes viral coat
proteins produced in plants as part of a plant-pesticide 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 viral coat proteins produced in plants
as part of a plant-pesticide (59 FR 60545), EPA did not propose any
numerical limitation on the amount of viral coat proteins 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 and this supplemental notice, and will consult with
the Secretary of HHS prior to issuing the final rule. Because the 1994
proposal was an 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 viral coat proteins in or on
food is not required.
V. Comments
A. Confidential Business Information
Information submitted as a comment 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 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 raise 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
[[Page 27155]]
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) EPA's conclusion that there are no substances outside of the
food supply that may have a cumulative toxic effect with residues of
viral coat proteins produced in plants as part of a plant-pesticide.
(2) EPA's conclusion that there are no substances outside of the
food supply that are related via a common mechanism of toxicity to
residues of viral coat proteins produced in plants as part of a plant-
pesticide to which humans might be exposed through non-occupational
routes of exposure.
Commenters who possess information on viral coat proteins causing
estrogenic effects 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 for
viral coat proteins.
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 containing
viral coat proteins applies to infants and children. No comments were
received on this rationale 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-300367A'' 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-300367A.'' Electronic
comments on this supplemental notice may be filed online at many
Federal Depository Libraries.
VII. References
(1) Gibbs, A. and B Harrison. 1976. Plant Virology: The Principles,
Chap. 1. J. Wiley Sons, New York.
(2) Matthews, R.E.F. 1981. Plant Virology. Chaps. 12, 16, and 19.
Second edition, Academic Press, New York.
(3) Provvidenti, R., R.W. Robinson, and H.M. Munger. 1984.
Occurrence of Zucchini Yellow Mosaic Virus in Curcubits from
Connecticutt, New York, Florida and California, Plant Disease 68:443-
446.
(4) Beemster, A.B.R. and J.A. de Bokx. 1987. Survey of Properties
and Symptoms of Potato Viruses, pp. 84-93 In: Viruses of Potatoes and
Seed Potato Production; J.A. de Bokx and J.P.H. vanderWant. PuDOC,
Wageningen, The Netherlands.
(5) Brun, G. 1991. Rhabdoviridae, Chap. 17, pp. 443-460; In: Atlas
of Invertebrate Viruses, eds. J.R. Adams and J.R. Bonami. CRC Press,
Boca Raton, FL.
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 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. 97-12785 Filed 5-15-97; 8:45 am]
BILLING CODE 6560-50-F