[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