[Federal Register Volume 59, Number 225 (Wednesday, November 23, 1994)] [Unknown Section] [Page 0] From the Federal Register Online via the Government Publishing Office [www.gpo.gov] [FR Doc No: 94-28822] [[Page Unknown]] [Federal Register: November 23, 1994] ======================================================================= ----------------------------------------------------------------------- ENVIRONMENTAL PROTECTION AGENCY 40 CFR Parts 152 and 174 [OPP-300369; FRL-4755-3] RIN 2070-AC02 Plant-Pesticides Subject to the Federal Insecticide, Fungicide, and Rodenticide Act; Proposed Rule AGENCY: Environmental Protection Agency (EPA). ACTION: Proposed rule. ----------------------------------------------------------------------- SUMMARY: The substances plants produce to protect themselves against pests and disease are considered to be pesticides under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) definition of ``pesticide'' (i.e., if they are ``. . . intended for preventing, destroying, repelling or mitigating any pest. . .''). These substances, along with the genetic material necessary to produce them, are designated ``plant-pesticides'' by EPA. EPA proposes to amend an existing regulation and to create a new regulation to clarify the relationship between plants and plant-pesticides and their regulatory status under FIFRA. EPA also proposes to exempt from FIFRA requirements classes of plant-pesticides that the Agency has determined pose low probability of risk and are not likely to cause unreasonable adverse affects on the environment. Recognizing the unique characteristics of plant-pesticides, the Agency proposes to create a new part in the CFR for regulations unique to plant-pesticides. DATES: Comments identified by the docket control number [OPP-300369] must be received on or before January 23, 1995. ADDRESSES: Submit written comments by mail to: Program Resources Section, Public Response and Program Resources Branch, Field Operations Division (7506C), Environmental Protection Agency, 401 M St., SW., Washington, DC 20460. In person, bring comments to Rm. 1132, Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA. Information submitted as a comment concerning this document may be claimed confidential by marking any part or all of that information as ``Confidential Business Information'' (CBI). Information so marked will not be disclosed except in accordance with procedures set forth in 40 CFR part 2. A copy of the comment that does not contain CBI must be submitted for inclusion in the public record. Information not marked confidential may be disclosed publicly by EPA without prior notice. All written comments will be available for public inspection in Rm. 1132 at the Virginia address given above from 8 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. FOR FURTHER INFORMATION CONTACT: By mail: Bernice Slutsky, Science and Policy Staff, Office of Prevention, Pesticides and Toxic Substances (7101), Environmental Protection Agency, 401 M St., SW., Washington, DC 20460, Telephone number: (202) 260-6900. SUPPLEMENTARY INFORMATION: I. Introduction EPA proposes to clarify the regulatory status, under FIFRA, of pesticidal substances produced in plants (plant-pesticides) and of plants that produce pesticidal substances and act as biological control agents. EPA defines a biological control agent as ``any living organism applied to or introduced into the environment that is intended to function as a pesticide against another organism declared to be a pest by the Administrator'' (40 CFR 152.3). EPA also proposes to exempt from FIFRA regulation certain types of pesticidal substances produced in plants that EPA believes do not warrant regulation. In the Federal Register of June 2, 1982 (47 FR 23928), EPA promulgated a final regulation under FIFRA section 25(b) that exempted all biological control agents, except for certain microorganisms, from the requirements of FIFRA. This exemption was promulgated because EPA found that the risks posed by biological control agents other than microorganisms were adequately addressed by other Federal agencies such as the U.S. Department of Agriculture's (USDA's) Animal and Plant Health and Inspection Service (APHIS) and the U.S. Department of the Interior. Although plants used as biological control agents were not specifically addressed in 40 CFR 152.20 or in the June 2, 1982, Federal Register document, EPA has considered these plants to be excluded from regulation under FIFRA through this exemption. EPA continues to believe that plants used as biological control agents are adequately regulated by other Federal agencies. However, EPA believes that the status of pesticidal substances produced in plants (i.e., plant-pesticides) requires regulatory clarification. Although plants used as biological control agents were exempted from FIFRA regulation under 40 CFR 152.20, substances that are extracted from plants and used as pesticides are not similarly exempted. For example, chrysanthemums produce pyrethrum, a substance that has insecticidal activity. Chrysanthemums that produce pyrethrum are exempt from regulation when used as biological control agents (i.e., living chrysanthemums), but pyrethrum itself, as the pesticide substance, is not exempt when it is extracted from chrysanthemum plants and applied to other plants as an insecticide. This distinction is reasonable in light of the potential for increased and unique exposures due to large-scale application of extracted pyrethrum to plants that do not naturally produce it. The use of extracted pyrethrum as an insecticide can involve exposure to the pesticide over large acreages, whereas the exposure associated with pyrethrum produced by living chrysanthemum plants would not be expected to reach such proportions. In addition, application of pyrethrum beyond the environment in which it is normally produced (i.e., beyond the living chrysanthemum plant) could result in new or unique exposures of nontarget organisms, including humans. Although it has been EPA's policy under FIFRA to regulate pesticidal substances that have been extracted from plants, to date the Agency has not clearly stated its policies for regulation of pesticidal substances that are produced in living plants and function in situ to protect the plant from pests or disease (i.e., not extracted from the plants). This proposed rule is designed to provide such clarification. FIFRA section 2(u) defines ``pesticide'' as: ``(1) any substance or mixture of substances intended for preventing, destroying, repelling, or mitigating any pest, and (2) any substance or mixture of substances intended for use as a plant regulator, defoliant, or desiccant. . . .'' The substances that are produced in plants to protect them against pests and disease are considered to be pesticides under the definition of FIFRA section 2, (i.e., if they are ``. . . .intended for preventing, destroying, repelling, or mitigating any pest. . .'') regardless of whether the pesticidal capabilities evolved in the plants or were introduced by traditional breeding or through the techniques of modern biotechnology. These substances, along with the genetic material necessary to produce them, are designated ``plant-pesticides'' by the Agency. There are a number of types of substances produced in plants that enable plants to resist pest attack and disease. These substances include both those pesticidal substances that would be considered normally a component of a plant and those that would be considered new to a plant. Examples of plant-pesticides that would be considered normally a component of a plant are phytoalexins (plant-produced substances that act against phytopathogenic microorganisms). An example of a plant-pesticide that would not be considered normally a component of a plant is the insecticidal delta endotoxin that is produced in the bacterium, Bacillus thuringiensis. This proposal would clarify the relationship between plants and plant-pesticides. It applies to all pesticidal substances produced in living plants, including bryophytes such as mosses, seedless vascular plants such as ferns, gymnosperms such as conifers, and angiosperms such as most major crop plants. This proposal would reaffirm that plants continue to be exempt under 40 CFR 152.20 and, under a new part 174 (in the 40 CFR) would codify which categories of plant-pesticides would be exempt and which would be regulated by EPA under FIFRA. Recognizing the unique characteristics of plant-pesticides, the Agency will, in the future, include, in part 174, other regulations specific to plant-pesticides. As part of the effort to develop this proposal, EPA requested advice from two scientific advisory committees at three meetings. On December 18, 1992, a Subpanel of the FIFRA Scientific Advisory Panel (SAP) was convened to review a draft proposed policy statement and to answer a series of scientific questions concerned primarily with EPA's proposed approach for plant-pesticides under FIFRA. On July 13, 1993, a Subcommittee of the EPA Biotechnology Science Advisory Committee (BSAC) was convened to address a series of scientific questions concerned primarily with EPA's proposed approach for plant-pesticides under the Federal Food, Drug, and Cosmetic Act (FFDCA). On January 21, 1994, a joint BSAC/SAP Subpanel was convened to address a series of scientific questions concerned with the scope of regulation under both FIFRA and FFDCA and guidance for data needs for the evaluation of plant- pesticides. This proposed rule is one of several documents published in today's issue of the Federal Register that address EPA's approach to regulating plant-pesticides. The other documents are: (1) A proposed policy statement that generally describes how EPA proposes to regulate plant- pesticides under FIFRA and the FFDCA (``Plant-pesticides Subject to the Federal Insecticide, Fungicide, and Rodenticide Act and the Federal Food, Drug, and Cosmetic Act; Proposed Policy''; (2) a proposed exemption from the requirement of a tolerance for categories of plant- pesticides that do not result in significantly different dietary exposures (``Plant-pesticides; Proposed Exemption from the Requirement of a Tolerance Under the Federal Food, Drug, and Cosmetic Act''; (3) a proposed exemption from the requirement of a tolerance for coat proteins from plant viruses (``Plant-pesticides; Proposed Exemption from the Requirement of a Tolerance Under the Federal Food, Drug, and Cosmetic Act for Viral Coat Proteins Produced in Plants'' and (4) a proposed exemption from the requirement of a tolerance for nucleic acids produced in plants as part of a plant-pesticide (``Plant- pesticides; Proposed Exemption from the Requirement of a Tolerance Under the Federal Food, Drug, and Cosmetic Act for Nucleic Acids Produced in Plants''). II. Statutory Authority This rule is being proposed under the authority of section 3 and section 25(a) and (b) of the Federal Insecticide, Fungicide, and Rodenticide Act (7 U.S.C. 136 et. seq.). FIFRA section 2(u) defines ``pesticide'' as: ``(1) any substance or mixture of substances intended for preventing, destroying, repelling, or mitigating any pest, and (2) any substance or mixture of substances intended for use as a plant regulator, defoliant, or desiccant . . . '' FIFRA section 3 provides that no person may distribute or sell in the United States any pesticide that is not registered under the Act. Before a product may be registered as a pesticide under FIFRA, it must be shown that when used in accordance with widespread and commonly recognized practice, it will not generally cause ``unreasonable adverse effects on the environment.'' FIFRA section 2(bb) defines the term ``unreasonable adverse effects on the environment'' as any unreasonable risk to humans or the environment, taking into account the economic, social, and environmental costs and benefits of the use of any pesticide. Thus, FIFRA involves a balancing of the risks presented by the use of the pesticide against the benefits associated with the use of that pesticide. In addition, FIFRA section 3(a) provides that, to the extent necessary to prevent unreasonable adverse effects on the environment, the Administrator may by regulation limit the distribution, sale or use of any pesticide that is not registered under FIFRA or subject to an Experimental Use Permit under FIFRA section 5 or subject to an emergency exemption under FIFRA section 18. Under FIFRA section 25(b), EPA may exempt, by regulation, any pesticide determined to be adequately regulated by another Federal agency, or of a character which is unnecessary to be subject to the Act in order to carry out the purposes of the Act. III. 40 CFR Part 174 EPA is proposing to set forth, under FIFRA, a new part in 40 CFR specifically for plant-pesticides regulated under FIFRA. In proposed part 174, as well as at Sec. 152.20, EPA would clarify the regulatory relationship between plants and plant-pesticides and, at Sec. 174.5, EPA would define the scope of regulation for plant-pesticides under FIFRA. Although EPA is not proposing in today's issue of the Federal Register specific regulatory requirements for plant-pesticides in part 174 (e.g., labeling and Experimental Use Permit requirements), EPA plans to propose such regulations in the future. In the interim period before these additional regulatory amendments are proposed and promulgated, EPA will use existing pesticide regulations (see 40 CFR parts 152 to 173 and 40 CFR parts 177 to 186) for plant-pesticides where applicable. However, these existing regulations were developed generally for traditional, chemical pesticides. Because of the unique characteristics of plant-pesticides, EPA recognizes that the existing regulations may not always be appropriate for these products. The characteristics of plant-pesticides such as both their production and use in plants; their biological properties; and their potential ability to spread and increase in quantity in the environment distinguishes them from traditional, chemical pesticides. The Agency therefore intends to apply the existing regulations to plant-pesticides in a manner that addresses the unique issues associated with plants. Producers are encouraged to consult with the Agency well in advance of any proposed activities involving plant-pesticides. (Refer to the Federal Register document entitled, ``Proposed Policy; Plant-pesticides Subject to the Federal Insecticide, Fungicide, and Rodenticide Act and the Federal Food, Drug, and Cosmetic Act.'') IV. Definitions Because of the unique nature of plant-pesticides, the Agency is proposing certain definitions that will apply to plant-pesticides only. These definitions are contained in the proposed regulatory text under 40 CFR 152.3, and in 40 CFR 174.3. The following unit describes the key definitions for plant-pesticides under FIFRA and the rationales underlying these definitions. A. Definition of Plant-pesticide EPA would define ``plant-pesticide'' under FIFRA as: A pesticidal substance that is produced in a living plant and the genetic material necessary for the production of the substance, where the substance is intended for use in the living plant. EPA is including the genetic material necessary to produce the substance in the proposed definition of plant-pesticide for a number of reasons. First, it is the genetic material that is introduced into the plant with the intent that it will ultimately result in a pesticidal effect. Additionally, EPA's regulation of pesticides is based on an evaluation of the potential for unreasonable adverse effects associated with the pesticidal substance, in this case, the pesticidal substance produced in the plant. Regulation also includes risk management considerations. A focus on the genetic material would permit the Agency to address the potential for the spread of the pesticidal substance in the environment through the spread of the genetic material necessary for the production of the substance. Moreover, the amount of pesticidal substance likely to be produced by the plant is also an important consideration that the Agency may, in some circumstances, be able to address through the inclusion of genetic material in the definition of plant-pesticide. In addition, including the genetic material in the definition of plant-pesticide would permit the Agency to address plant- pesticides during stages of the plant's life cycle or in plant parts where the pesticidal substance itself is not produced or is produced in very small amounts (e.g., in pollen or seed). In these cases it is technically easier to verify the presence of the genetic material than the pesticidal substance. B. Definition of Active and Inert Ingredients The regulation of pesticides under FIFRA entails the identification of ``active ingredients'' and ``inert ingredients.'' Under FIFRA section 2, the term active ingredient means ``. . . an ingredient which will prevent, destroy, repel, or mitigate any pest. . . [or acts as a plant regulator, defoliant or desiccant].'' The term inert ingredient means ``. . . an ingredient which is not active.'' EPA recognizes that plant-pesticides have certain characteristics that are different from those of more traditional chemical pesticides. EPA believes that the overall characteristics of plant-pesticides require specifically tailored active and inert ingredient definitions. In light of this consideration, EPA proposes to use the following definitions for plant-pesticides. Active ingredient, when referring to plant-pesticides only, means a pesticidal substance that is produced in a living plant and the genetic material necessary for the production of the substance, where the substance is intended for use in the living plant. Inert ingredient, when referring to plant-pesticides only, means any substance, such as a selectable marker, other than the active ingredient, and the genetic material necessary for the production of the substance, that is intentionally introduced into a living plant along with the active ingredient, where the substance is used to confirm or ensure the presence of the active ingredient. Note that the plant-pesticide active ingredient is the plant- pesticide and therefore the proposed definition of active ingredient for plant-pesticides is the same as the definition of plant-pesticide. The plant-pesticide product includes both the active and inert ingredients. The definition of plant-pesticide and the active and inert ingredient definitions would include all of the genetic material ``necessary for the production'' of the pesticidal and inert substance. The following genetic regions are considered ``necessary for the production'' of the plant-pesticide active and inert substances: (1) The genetic material that encodes for the pesticidal substance or leads to the production of the pesticidal substance, and (2) regulatory regions such as promoters, enhancers, and terminators. The genetic material can either directly encode for the pesticidal substance or may encode for enzymes that lead to the production of a pesticidal substance (e.g., phenylalanine ammonia-lyase (PAL) catalyzes the first reaction in the synthesis of such phytoalexins as pterocarpans in Leguminosae and furanocoumarins in Solanaceae and Umbelliferae; Ref. 4). It might also include genetic regions encoding for RNA that acts as the pesticidal substance or leads to the production of the pesticidal substance (e.g., antisense mRNA). The active and inert ingredients would also include any regulatory regions, such as promoters, that control the expression of the genetic material encoding for the pesticidal or inert substance or leading to the production of the pesticidal or inert substance and are introduced into the plant along with that gene. For example, a different regulatory element could lead to the production of the pesticidal substance in new plant parts or for new durations, resulting in new exposure scenarios. The genetic material ``necessary for the production'' of the plant- pesticide active and inert substances does not include genetic regions that are not involved in DNA expression (i.e., noncoding, nonexpressed sequences such as linkers, adapters, homopolymers, and sequences of restriction enzyme recognition sites). However, the Agency would require information concerning these sequences if it determines that such information is necessary for the evaluation of the active or inert ingredient. There may be genetic material encoding other functions (e.g., genetic material intended to alter the amount of carbohydrate in the plant) that are introduced into the plant along with the active and inert ingredients. These activities would be subject to the Food and Drug Administration (FDA) authorities. V. Proposed Exemptions for Plant-pesticides EPA has attempted to identify those types of plant-pesticides that have greater potential for environmental and/or human health risks and to focus its regulatory scrutiny on these plant-pesticides. To exempt from regulation those plant-pesticides having low potential for risk, EPA is proposing to employ its exemption authority under FIFRA section 25(b). FIFRA section 25(b)(2) allows the Agency to exempt a pesticide from the requirements of FIFRA if it is of a character unnecessary to be subject to the Act in order to carry out the purposes of the Act. Through FIFRA section 25(b)(2), EPA proposes to exempt certain categories of plant-pesticides that EPA believes pose low probability of risk and are not likely to cause unreasonable adverse effects even in the absence of any regulatory oversight under FIFRA and, thus, are of a character unnecessary to be subject to the Act. Those plant- pesticides not exempted would form the scope of EPA's regulatory scrutiny under FIFRA. EPA finds that the plant-pesticides it is proposing to exempt have a low probability of risk and have potential benefits associated with them (e.g., economic benefits to farmers and reducing the need for chemical pesticides) that outweigh any potential risks associated with them, and that the low probability of risk does not justify the cost of regulation. Therefore, the Agency proposes under 40 CFR 174.5 to exempt, from FIFRA regulation, the categories of plant-pesticides that EPA has identified as those that are likely to pose little risk and are not likely to cause unreasonable adverse effects on the environment even in the absence of regulatory oversight. While EPA's analysis of the potential risks and benefits of plant- pesticides has led the Agency to the conclusion that some categories of plant-pesticides warrant regulation while others do not, the Agency cannot foresee all potential adverse effects to human health or the environment which may potentially arise for testing and use of specific plant-pesticides. Thus, in Sec. 174.7 EPA is proposing to require reporting of information on adverse effects from the testing and use of plant-pesticides that EPA is proposing to exempt in Sec. 174.5. Proposed Sec. 174.7 is meant to address unforeseeable events resulting from use of such pesticides. EPA believes that such events are likely to be extremely rare; however, Sec. 174.7 is a means of ensuring that any potential risk is addressed and that the Agency's data base is as complete as possible. Information on potential unreasonable adverse effects would be required to be reported if such information is obtained, from any source, by any person who sells or distributes a plant-pesticide. Failure to comply with Sec. 174.7 would be an unlawful act under FIFRA section 12(a)(2)(S) and could result in an enforcement action (for penalties) under FIFRA section 14. In addition, FIFRA section 6(a)(2) applies to plant-pesticides that would not be exempt under this proposed rule. As with traditional pesticides, the underlying considerations in analyzing risks posed by plant-pesticides are the potential for exposure to the pesticidal substance and hazards of the pesticidal substance to humans, other nontarget organisms, and the environment. For plant-pesticides, exposure and hazard will be determined by the chemical and toxicological properties of the pesticidal substance and the biological characteristics of the plant that is producing the substance. The properties of the plant-pesticide, including the mechanism by which it affects the target pest, will determine the potential for hazards to nontarget organisms, including humans. The type of organism exposed to the plant-pesticide will be determined by the characteristic of the plants that produce the substance and the environment where the plants are grown; e.g., whether the production of the substance is limited to particular plant parts, the organisms that normally associate with the plant, and the acreage and location planted. An important consideration not seen with traditional pesticides is the potential for spread of the plant's genetic material. Because plants can reproduce sexually and/or asexually, the ability to produce the plant-pesticide could spread through the agro- or natural ecosystems, particularly if wild relatives acquire the ability to produce the plant-pesticide through successful hybridization. Such hazard and exposure considerations form the bases of the three exemptions, discussed in Units V.A., V.B., and V.C. of this preamble, that the Agency is proposing for plant-pesticides under FIFRA. The benefits associated with use of some categories of plant- pesticides include the economic benefit to farmers for use of plant- pesticides in circumstances where traditional pesticides may not be as effective (e.g., for some systemic plant pests) or may be more expensive, thus increasing crop yield and/or reducing farmers' costs. An additional benefit is the environmental benefit associated with potential reduced use of pesticides that may be less environmentally benign than these plant-pesticides. A. Exemption of Plant-pesticides Derived from Closely Related Plants A primary consideration in evaluating plant-pesticides is the potential for new exposures of nontarget organisms to the pesticide. If a plant normally produces a pesticidal substance, organisms that come in contact with the plant have likely been exposed to that substance in the past, perhaps over long periods of time. The potential for new exposures to occur would be very low. In contrast, if a plant-pesticide is not normally produced by a plant, the organisms that come in contact with the plant may never have been exposed to the substance. For instance, certain spiders produce a toxin that is targeted for their insect prey. Plants are not known to produce this toxin in nature or in cultivation. If this toxin were to enter the gene pool of specific plants, organisms that had never previously been exposed to the toxin could now be exposed. Prior to the introduction of the toxin into these plants, only the insect prey of the spider would potentially be exposed to the toxin. If plants could now express the toxin, a different or larger group of organisms could be exposed to it, possibly resulting in adverse effects to these organisms. For instance, insects that feed on the plant could be exposed to the toxin. If the toxin is found in pollen, pollinators could also be exposed. EPA is proposing to concentrate its regulatory efforts under FIFRA on those plant-pesticides that are new to the plant and, thus, have the greatest potential for exposing nontarget organisms to a new pesticidal substance. The Agency is proposing to exempt from FIFRA regulation those plant-pesticides that are normally a component of (not new to) a plant. In defining, for regulatory purposes, those substances it considers to be normally a component of a plant, the Agency is presenting three approaches to the proposed exemption for public comment. In selecting among these three options, the Agency will consider how well each of the options: (1) Distinguishes, on a risk basis, those plant-pesticides that would result in new environmental exposures from those that would not; (2) provides a standard of sufficient regulatory clarity so that the public, industry, and the Agency can easily identify those plant-pesticides that would be subject to regulation; (3) does not place an undo burden on producers/ developers; and (4) creates as similar a scope of regulation as possible for this exemption under FIFRA as EPA is proposing under FFDCA, given the differences in mandate and structure of the two statutes. The three options are described below followed by a description of terms used in the options in Unit V.A.4. of this preamble and an analysis of the options in Unit V.A.5. of this preamble. For the reasons discussed in Unit V.A.5. of this preamble, EPA prefers Option 1 over Options 2 or 3. 1. Option 1: Plant-pesticides derived from sexually compatible plants. This approach is based on the concept of sexual compatibility. The Agency believes this concept describes a measure of relatedness between plants and views plant-pesticides moved between sexually compatible plants as not new to the plant. The use of the standard of sexual compatibility is embodied in the following language from the proposed regulatory text: [Plant-pesticides are exempt from FIFRA requirements if:] . . .The genetic material that encodes for a pesticidal substance or leads to the production of a pesticidal substance is derived from plants that are sexually compatible with the recipient plant and has never been derived from a source that is not sexually compatible with the recipient plant;. . . 2. Option 2: Plant-pesticides derived from plants within the same genus. A second approach that EPA is considering for defining when a plant-pesticide is new to the plant is a standard based on taxonomy. Under this approach, the standard would rely on the taxonomic grouping of genus; plant-pesticides moved between plants in the same genus would be exempt. The assumption under this approach is that the genus grouping correlates with a relatively high degree of relatedness among plants even though not all plants in a genus are sexually compatible. Similarity in traits ranging from flower morphology to the presence of particular alkaloids and flavonoids, for example, have been used to determine whether to classify a plant species in a particular genus and these traits likely bespeak a high degree of relatedness. The language defining this option would be as follows: [Plant-pesticides are exempt from FIFRA requirements if:] The genetic material that encodes for a pesticidal substance or leads to the production of a pesticidal substance is derived from plants that are within the same genus as the recipient plant [regardless of sexual compatibility] and has never been derived from a source outside of that genus; 3. Option 3: Plant-pesticides derived from plants within the same genus or from sexually compatible plants. The third approach EPA is considering combines the above two standards of taxonomy and sexual compatibility. The standard under this option would rely primarily on the taxonomic grouping of genus as a measure of relatedness. Recognizing that some plants that are sexually compatible are classified in different genera and assuming that sexual compatibility bespeaks a high degree of relatedness, EPA also includes a provision extending the exemption to include sexually compatible plants from any genera. The language defining this option would be as follows: [Plant- pesticides are exempt from FIFRA requirements if:] The genetic material that encodes for a pesticidal substance or leads to the production of a pesticidal substance: (1) Is derived from plants that are within the same genus as the recipient plant [regardless of sexual compatibility] or, is derived from plants that are sexually compatible with the recipient plant; and (2) Has never been derived from a source outside the same genus that is not sexually compatible with the recipient plant. 4. Terms used in the options. The phrase ``genetic material that encodes for the pesticidal substance or leads to the production of the pesticidal substance'' refers to genetic material that: (1) Directly encodes for the pesticidal substance; (2) encodes for enzymes that lead to the production of a pesticidal substance (as in the example of the PAL gene discussed in Unit IV. of this preamble); or (3) encodes for RNA that acts as a pesticide or leads to the production of a pesticidal substance (e.g., antisense RNA). For the purposes of the options for this exemption under FIFRA, this phrase is not intended to include regulatory regions or noncoding, nonexpressed nucleotide sequences when the genetic material encoding for or leading to the production of the pesticidal substance would otherwise be exempt. For this specific exemption, these regulatory regions and noncoding, nonexpressed nucleotide sequences may be derived from any source. For example, if a viral promoter attached to a corn structural gene encoding a pesticidal substance is introduced into another corn variety, the structural gene and the viral promotor genetic construct would meet the criteria of the options for this exemption. Note that whereas regulatory elements are not, for the purposes of the proposed exemptions, considered part of the genetic material ``that encodes for a pesticidal substance or leads to the production'' of a pesticidal substance, regulatory elements are considered part of the genetic material ``necessary for the production'' of a pesticidal substance under the definitions of the plant-pesticide active and inert ingredients (see Unit IV. of this preamble). The definition for ``sexually compatible'' means being capable of forming a viable zygote through the fusion of two gametes and can include the use of bridging crosses and wide cross breeding techniques such as surgical alteration of the plant pistil, bud pollination, mentor pollen, immunosuppressants, in vitro fertilization, pre- and post-pollination hormone treatments, manipulation of chromosome numbers, and embryo culture. It can also include, for the purposes of this exemption, ovary and ovule cultures. EPA believes that the production of viable zygotes through these techniques indicates a sufficient level of relatedness between the parental plants involved to be included under the rubric of ``sexually compatible.'' The phrase ``. . . has never been derived from a source that is not sexually compatible with the recipient plant . . .'' is meant to indicate in the proposed regulatory text that the genetic material would not qualify for the exemption if it is introduced into a plant from a sexually incompatible source and subsequently introduced into other sexually compatible plants. An example of such a situation would be if the Bacillus thuringiensis delta endotoxin is introduced into wheat and the endotoxin producing wheat subsequently hybridized with rye using wide cross techniques to produce triticale. The endotoxin produced in the triticale would not be eligible for the exemption. 5. Analysis of options. EPA's goal in developing these options for defining an exemption under FIFRA is to identify those plant-pesticides with a higher potential for new environmental exposures to nontarget organisms. Under Option 1, the Agency would consider plant-pesticides produced in sexually compatible plants to be least likely to result in these new exposures. Since traits can be passed through a plant population by sexual recombination, it is reasonable to predict that, in a sexually compatible population, new exposures of organisms that associate with plants in the population to the pesticidal substance are unlikely. Sexually compatible plants are more apt to share traits than are unrelated plants. It is a common expectation that similarity is associated with the degree of relatedness. Natural hybridization and selection have produced groups of plants which have a common gene pool. Generations of artificial hybridization practiced to produce improved crops for cultivation have tended to increase the extent of relatedness among elements of a broader segment of agricultural plants. The practice of saving seed from desirable plants has been going on for thousands of years and controlled crosses to produce plant hybrids have been documented since the eighteenth century. Since the rediscovery of Mendel's work on the inheritance of traits, there is a base of experience of 50 to 100 years of breeding for most major crops. During that time, it has been common agricultural practice to cross sexually compatible wild relatives with crop plants to develop crop varieties with better pest resistance. Techniques such as genetic mapping reveal the presence of genetic loci in cultivated plants that previously were considered to be present only in the wild species. Sexually compatible crop varieties are also crossed with each other to achieve better pest resistance in their progeny. Because of these common practices, the potential for significantly different environmental exposures from current crop plants is likely to be low. EPA proposes to extend the concept of sexual compatibility to include wide crosses because wide crosses are commonly used to expand the plant gene pool for varietal improvement, and EPA believes that a fairly high degree of relatedness between the parental plants is indicated when a wide cross produces a viable zygote. However, for regulatory purposes it is somewhat difficult to define what constitutes a wide cross since techniques may change over time. EPA is thus proposing, for the purposes of this proposed rulemaking, a definition of wide crosses that is based on existing techniques with a provision to add new techniques if they meet the definition. Options 2 and 3 both rely on taxonomy, and this standard may also represent an acceptable degree of relatedness. Plant species within the same genus may have become separated by geography, timing of pollination, or other factors to form two distinct populations no longer sexually compatible. Events such as mutation and environmental selection can reinforce the isolation and uniqueness of the gene pools. However, the ability to overcome these incompatibility barriers between species in the same genera through human intervention (e.g., bridging crosses and wide crosses) is evidence that such plants are fairly closely related. The majority of successful wide crosses to date have occurred between species within the same genus. The second option is based solely on the taxonomic standard of genus. Sexual compatibility (including the use of bridging crosses and wide crosses) with the recipient plant would not be a criterion. The third option relies primarily on taxonomy but also includes the standard of sexual compatibility. Unlike Option 2, under this option, plant-pesticides derived from a plant outside of the same genus as the recipient plant could still be eligible for the exemption if sexual compatibility between the source and the recipient plant is demonstrated. The use of a taxonomic standard may, from a regulatory perspective, be somewhat clearer than a standard based solely on sexual compatibility (including bridging and wide crosses). However, taxonomy may be a more artificial standard than sexual compatibility as a predictor of different environmental exposures of a plant-pesticide, particularly for unmanaged or semi-managed plants. Isolation, adaptation to unique environments, and low natural rates of gene flow even between populations of the same species characterize many natural populations. For these types of plants, the taxonomic standard used in Options 2 and 3 may not be as appropriate as the sexual compatibility standard used in Option 1 with regard to novel exposures to plant- pesticides produced in unmanaged or semi-managed plants. In addition, classification of plants in different genera is not fixed and could change over time and between scientific authorities. Option 1 is more compatible than either Option 2 or 3 with EPA's preferred approach to plant-pesticides under FFDCA. Under FFDCA, EPA sets tolerances for pesticide residues in foods. EPA may also exempt pesticides from the requirement of a tolerance when such tolerance is not needed to protect the public health. EPA is proposing to exempt from FFDCA requirements certain plant-pesticides that would not result in significantly new dietary exposures as it is proposing to exempt plant-pesticides that would not result in new environmental exposures from FIFRA requirements. Under both statutes, EPA's preferred approach uses the standard of sexual compatibility presented in Option 1 in this document. In addition, using a taxonomic standard alone (Option 2) is not considered a viable option under FFDCA (see Federal Register document entitled, ``Plant-pesticides; Proposed Exemption from the Requirement of a Tolerance Under the Federal Food, Drug, and Cosmetic Act.'' For some crop plant varieties, e.g., potatoes, vegetative propagation is commonly used in addition to breeding. Since vegetatively propagated plants have the same genetic makeup, EPA intends that a plant-pesticide produced in a vegetatively propagated plant would meet the criteria of Option 1 as long as the plant- pesticide is either produced during vegetative propagation or, during breeding, the original genetic source of the plant-pesticide is sexually compatible with the recipient plant, as defined in the proposed regulatory text. A plant-pesticide produced in vegetative plants would meet the criteria of Option 2 and 3 as long as the plant- pesticide is produced during vegetative propagation or the original genetic source of the plant-pesticide is in the same genus as or, in the case of Option 3, is sexually compatible with the recipient plant. None of the options presented in this unit are intended to exempt plant-pesticides which are significantly different in structure or function from the plant-pesticide as it occurs in the source plant. Such significantly modified plant-pesticides would not be eligible for exemption under any of the options. Rearrangements or modifications of the sequence encoding a plant-pesticide, for example, could result in plant-pesticides with significantly different structures and/or functions from those in the source plant and these would not be exempt. If this type of modification were to occur, the potential for new and different exposures in the environment could be significant. Under all of the approaches discussed in this unit, the Agency has evaluated whether changes in the levels of plant-pesticides that plants normally produce would warrant regulation under FIFRA. (Ref. 1) The Agency's analysis indicates that changes in the levels of such plant- pesticides expressed by a plant could result in increased or decreased exposures of nontarget organisms to a plant-pesticide. However, EPA believes, for the reasons outlined below, that the potential for unreasonable adverse effects from these exposures is low and these types of plant-pesticides do not warrant regulation under FIFRA. In deciding whether and how to regulate such plant-pesticides, EPA first considered whether an increase in the levels of these plant- pesticides is likely to exceed the ranges normally found within and between plant varieties (both cultivated and uncultivated). EPA believes that increases in the levels of such plant-pesticides are not likely to result in overall significantly different exposures of nontarget organisms to the pesticide. The level of production of such pesticidal substances normally varies among related plants because of differences in genetic makeup and environmental conditions. This variation, in turn, results in natural variations in the levels of exposure to the pesticide. Nontarget organisms that associate with the plants, such as birds and insect pollinators, are exposed to a range of such plant-pesticide levels in nature. EPA also considered the extent to which any substance can be increased in cultivated plants without unwanted effects on other, desirable characteristics of the plant (e.g., yield or palatability of fruit). In general, breeders balance all of these characteristics in developing marketable plant varieties. Considerations of characteristics such as yield could serve to mitigate against exceeding certain ranges of pesticide levels. Agricultural crop plants, those most likely to be grown in large acreages with concomitant large exposures, are not likely to be in the higher portion of the expression range because of these constraints and are not likely to produce as broad a range of levels of plant-pesticides that plants normally produce. EPA anticipates that the majority of agricultural crop plants with modified levels of plant-pesticide expression will fall within existing ranges of pesticide levels and does not anticipate that increasing the level of a plant-pesticide that is normally a component of a plant would lead to a signficantly different spectrum of exposure to the plant-pesticide. There are also difficulties in establishing what constitutes ``significantly higher levels'' for regulatory purposes. At the July 13, 1992 meeting, the BSAC Subcommittee was specifically asked and the subcommittee extensively discussed approaches to determining what constitutes significantly higher levels of a plant pesticide. During discussion at the meeting, the BSAC Subcommittee indicated it would be very difficult to establish standards for ``significantly higher levels'' since no formal complete data base of plant constituents and their concentration ranges exists. Because of these difficulties, the BSAC Subcommittee final report did not suggest a scope criterion based on ``significantly higher levels.'' For these reasons, EPA is not proposing, under FIFRA, to regulate using a criterion based on ``significantly higher levels'' of a plant-pesticide. Consistent with the Agency's proposed statement of policy on plant- pesticides, EPA recognizes that plant defense compounds found in plants that are not sexually compatible, or in other organisms such as microorganisms, can be structurally and functionally equivalent to compounds found in the recipient plant or in a plant sexually compatible with the recipient plant. EPA is willing to consider, in the future, exemptions for plant-pesticides (as are proposed for viral coat proteins) if a producer can provide evidence that the plant-pesticide is structurally and functionally equivalent to a plant-pesticide found in the recipient plant or in a plant sexually compatible with the recipient plant. Specifically, the Agency is willing to consider development of procedures and criteria for these plant-pesticides. Please see Request for Comment unit, Unit VII., of this preamble for a fuller discussion of how such exemptions might be granted in future rulemakings. B. Exemption of Plant-pesticides That Act Primarily by Affecting the Plant One of EPA's primary goals in regulating pesticides is to control the potential for adverse effects of pesticides on nontarget organisms. An important component in the evaluation of this potential is the way in which the pesticidal substance acts on the target pest since it would also likely affect nontarget organisms through the same mechanism. A pesticidal substance that acts directly on the target pest through a toxic mechanism of action might also exert a similar effect on other organisms. For example, a substance that acts by inhibiting DNA synthesis of the pest could inhibit DNA synthesis in other nontarget organisms.Toxic mechanisms of action include, but are not limited to, those that affect: (i) Membrane permeability, (ii) cell division, (iii) gene expression, (iv) DNA replication, or (v) other metabolic functions (Ref. 3). Pesticidal substances can also act through mechanisms that are less likely to be directly toxic. Although it is possible for these substances to adversely affect nontarget organisms, the Agency believes that, in most cases, they pose significantly lower levels of environmental risk than plant-pesticides with a generalized toxic mechanism of action. Plant-pesticides that are less directly toxic generally act primarily by affecting the plant so that the pest is inhibited from attaching to the plant, penetrating the plant's surface or invading the plant's tissue. For example, if a plant is modified so that it can counter specific disease-producing compounds by inactivating them, it is less likely that organisms that interact with the plant in other, more beneficial ways will be affected. Similarly, a plant may be modified to produce defense structures such as layers of cork cells in response to infection by fungi or bacteria. These structures form a barrier to further penetration by the pests and may block the spread of any toxins. Other, nontarget organisms that do not stimulate this response are not likely to be adversely affected. The Agency believes that it would be appropriate to exempt from regulation, under FIFRA, plant-pesticides that act through mechanisms such as these. EPA believes that by focusing its regulatory attention on plant- pesticides that act through toxic mechanisms, it will be able to focus on those plant-pesticides presenting higher levels of risk potential. The proposed regulatory text presents criteria to define mechanisms of action that are not directly toxic to the target pest. EPA proposes that producers would assess whether they meet the criteria presented in the proposed regulatory text. Proving eligibility would rest with the producer claiming the exemption and the producer could meet this responsibility by producing documentation of their determination should a question arise concerning their claim for exemption. If the producer's assessment is incorrect and the plant- pesticide does not qualify for the exemption, anyone selling or distributing the plant-pesticide would be subject to enforcement actions for selling or distributing an unregistered pesticide. Producers would be encouraged to consult with the Agency with regard to specific cases. EPA is also considering whether to extend this exemption to include substances such as plant hormones because they act by ``primarily affecting the plant'' and do not act directly on a target pest (see Unit VII.B. of this preamble and the proposed statement of policy published elsewhere in today's issue of the Federal Register entitled ``Proposed Policy; Plant-pesticides Subject to the Federal Insecticide, Fungicide, and Rodenticide Act and the Federal Food, Drug, and Cosmetic Act''). C. Exemption of Coat Proteins from Plant Viruses Coat proteins are those substances that encapsulate and protect the genetic material of certain viruses. In some cases, when the genetic material encoding for the coat protein is introduced into a plant's genome, the plant is able to resist subsequent infections by the same virus or related strains (termed viral coat protein mediated resistance or vcp-mediated resistance). The Agency is proposing to exempt the genetic material encoding for the coat protein and the coat protein itself when these are introduced into a plant to effectuate viral coat protein mediated resistance. The Agency's proposal is based on a number of considerations which, when taken together, bring EPA to the conclusion that coat proteins used in vcp-mediated resistance pose low probability of risk and would not cause unreasonable adverse effects. These considerations include the low potential for adverse affects to nontarget organisms and the potential benefits (environmental and economic) of utilizing vcp- mediated resistance. To promote the fullest discussion of the issue possible, however, the Agency is also offering for discussion an alternative, more limited exemption. The two options are described below followed by an analysis of the options in Unit V.C.3. of this document. 1. Option 1: Exemption of all coat proteins from plant viruses. Under EPA's preferred option, all coat proteins from plant viruses (vcp-mediated resistance coat protein) and the genetic material encoding for the coat protein would be exempt from FIFRA requirements when produced in plants for viral coat protein mediated resistance. This exemption would include the regulatory regions and noncoding, nonexpressed sequences needed to introduce the genetic material encoding for the viral coat protein into the plant. This exemption is embodied in the proposed regulatory text. 2. Option 2: Exemption of coat proteins from plant viruses produced in plants with low potential for outcrossing to wild relatives. Under this exemption, the Agency would limit its exemption of vcp-mediated resistance coat proteins to those viral coat protein/plant combinations that would have the least potential to confer selective advantage on free-living wild relatives. The regulatory language defining these viral coat protein/plant combinations would be as follows: The pesticidal substance is a coat protein from a plant virus and the genetic material necessary to produce the coat protein has been introduced into a plant's genome, and the plant has at least one of the following characteristics: (1) The plant has no wild relatives in the United States with which it can successfully exchange genetic material, i.e., corn, tomato, potato, soybean, or any other plant species that EPA has determined has no sexually compatible wild relatives in the United States. (2) It has been demonstrated to EPA that the plant is incapable of successful genetic exchange with any existing wild relatives (e.g., through male sterility, self-pollination). (3) If the plant can successfully exchange genetic material with wild relatives, it has been empirically demonstrated to EPA that existing wild relatives are resistant or tolerant to the virus from which the coat protein is derived or that no selective pressure is exerted by the virus in natural populations. For the purposes of this option, ``introduced into the plant's genome'' would mean movement of nucleotide sequences into the genetic material in a plant cell's nucleus, mitochondria, chloroplasts, and any other plastids. ``Successfully exchange genetic material'' would mean capable of forming zygotes viable in the laboratory and/or field through the fusion of two gametes. Under this option, if a plant is not on the list of plants with no wild relatives in criterion (1), a producer would be required to submit a written request for a determination by EPA as to whether their viral coat protein/plant combination meets criterion (1), i.e., the Agency would have to determine that this particular plant species has no wild relatives in the United States. If criterion (1) could not be met, the producer would have to submit information to the Agency to show that criterion (2) is met or submit empirical evidence that criterion (3) is met. 3. Analysis of options. The Agency's preferred option of exempting all vcp-mediated resistance coat proteins is based on the limited potential for adverse effects to nontarget organisms and/or new exposures to the coat protein and the potential environmental and economic benefits from using vcp-mediated resistance. Environmental benefits associated with the use of viral coat proteins include the reduction of the use of chemical pesticides for viruses that are spread by vectors (usually insects). Chemical pesticides are used for those crop plants where the most effective method of protection against viral attack is by controlling the vector. These pesticides may not be environmentally benign. The expression of viral coat proteins by plants for protection from viral infection would likely reduce the amount of chemical pesticide used to control the vectors. In addition to environmental benefits associated with the use of viral coat proteins, an effective method for controlling virus infection will have economic benefits. Plant viruses create economic losses for a vast variety of crops by reducing yields and negatively affecting the quality of the crop. Yield losses and quality effects for a specific crop may vary depending on the host plant and strains of the virus present, the incidence and activity of vectors, timing of the infection, health and nutritional state of the plant, and weather (Ref. 5). Presently, growers may need to use several control methods during a crop season in an attempt to prevent viral infection and dissemination, primarily by planting virus free material (for mechanically transmitted viruses) and by controlling plant virus vectors, such as insect populations (for vector transmitted viruses). Insecticides, nematicides, and fungicides are all used for vector control with varying success, depending upon the virus/vector relationship and vector efficiency. Plants developed through conventional breeding techniques offer some degree of virus resistance. Such resistance may not be uniform or the virus may develop new strains. However, breeding for resistance has not been successful for the majority of field crops and, in particular, vegetable crops that are severely affected by viruses (Ref. 6). In enabling plants to resist viral attack, viral coat proteins act in a very specific fashion, apparently adversely affecting only viruses by blocking or limiting their ability to infect, replicate, and/or translocate within the plant. This specificity minimizes the potential for viral coat proteins produced in plants to adversely affect nonviral organisms. In addition, plants in nature and in the agro-ecosystem frequently exhibit viral infections; nontarget organisms, including humans, have been and continue to be exposed to the viral coat proteins with no observed adverse effects. The possibility that environmental risk might be associated with the use of vcp-mediated resistance was discussed at the December 18, 1992 FIFRA Scientific Advisory Panel (SAP) Subpanel meeting (see Unit VI. of this preamble for a more thorough discussion of the issues discussed by EPA's science advisory committees). EPA agrees with the conclusions of the SAP Subpanel and in developing its proposal has utilized the advice of the Subpanel to supplement EPA's own evaluation of the scientific literature (Ref. 2). The considerations discussed by the Subpanel included: (1) The potential for new viruses to be formed through transcapsidation (also called heterologous encapsidation) and recombination, (2) the potential for synergistic infections, (3) the potential for seed transmission, and (4) the potential for the development of selective advantage in wild relatives through successful hybridization with the plant producing the viral coat protein. The SAP Subpanel report offered advice on these potential risk considerations and this advice is incorporated into the discussion below. Most plant viruses are composed of genetic material enclosed in a protein coat. For these viruses, the coat protein is the site of interaction with the host plant at several stages of the viral cycle (e.g., virus replication and movement within the plant). The coat protein also plays an essential role in transmission by vectors such as insects. The issue of transcapsidation revolves around the question: if a plant that produces a vcp-mediated resistance viral coat protein from Virus A is infected by Virus B, can the Virus B genome be encapsidated by the Virus A derived vcp-mediated resistance coat protein synthesized by the plant? The consequence of such transcapsidation is the possible extension of the host range of the virus through the possible transmission of the Virus B genetic material by vectors that would not normally transmit Virus B and possible infection of plants that would not normally be exposed to and/or infected by virus B. Heterologous encapsidation or transencapsidation has been observed both in vitro and in vivo between coinfecting whole viruses. However, transencapsidation between coinfecting viruses occurs more frequently between related viruses than unrelated viruses. Although some researchers have examined this question, there is no evidence that transencapsidation involving vcp-mediated resistance coat proteins produced in plants would occur at a higher frequency than has been observed with coinfecting whole viruses. With regard to transencapsidation involving vcp-mediated resistance coat proteins and horizontal transmission, the SAP Subpanel concluded that transencapsidation and transmission to other plants would most likely occur at low levels or would not occur, depending on: (1) The level of vcp-mediated resistance coat protein being produced by the plant (larger concentrations of vcp-mediated resistance coat protein would increase the probability of transcapsidation); (2) the efficiency of transencapsidation (this varies for transencapsidation of whole viruses); and (3) the efficiency of virus acquisition by the virus vector. For viruses in which a specific protein-RNA-helper factor complex is essential for transencapsidation or transmission to occur, transmission is virtually impossible. With regard to the potential for recombination between the plant- encoded coat protein and coat protein from an infecting virus different from the virus contributing the coat protein gene, the consequence of such recombination is the potential for the formation of a new virus. The December 18, 1992, SAP Subpanel concluded that recombination is not a risk consideration meriting regulatory oversight. Most recombination events demonstrated to date involve either a debilitated virus under strong selection pressure for restoration of the wildtype virus, or the exchange of terminal regulatory sequences. In both conditions, recombination was only demonstrated between very similar or identical viruses. New viruses are thus unlikely to arise through a recombinational event involving substitution of the vcp-mediated resistance coat protein genetic material for the coat protein genetic material of the infecting virus. Should variants of a virus arise through recombination, these variants would be subject to selection/ competitive pressures throughout the infection cycle as are variants that arise from recombination between replicating viruses. In addition, there is no evidence that recombination between plant-produced coat proteins and an infecting virus would occur at greater frequencies than currently occur in nature between replicating viruses. Synergistic-infection occurs when two viruses infect the same plant, causing more severe damage than would occur if either virus alone infected the plant. With regard to the potential for synergistic- infection, the SAP Subpanel stated that plants expressing Virus A vcp- mediated resistance coat proteins do not express a synergistic response when the plant is inoculated with Virus B that potentially could act synergistically with Virus A, either because coat proteins are not involved in synergy, or because the level of expression of the protein is too low to potentiate the interaction. In some species of plants, infecting viruses can be transmitted vertically to progeny plants through seed. The question posed with vcp- mediated coat proteins is whether their presence in the plant might affect seed transmission of infecting viruses. With regard to the possibility of coat protein modifications affecting the ability of seed to transmit viruses, the SAP Subpanel report states that in two cases where the viral genetics of seed transmission of viruses has been analyzed, genes other than those encoding the coat protein genes are involved in potentiating the transmission. There is no reason a priori to believe that introduction into the plant of viral coat protein genes would affect the level of vertical transmission of viruses through seed. The possibility that transfer of the vcp-mediated resistance coat protein gene to a wild relative of the modified crop plant might bestow a selective advantage on the wild relative has also been examined by the SAP Subpanel and the Agency. The SAP Subpanel report indicates that even if the low probability events of transfer and expression of the coat protein gene from crop plant to wild relative occur, the wild plant may not acquire a selective advantage. The Subpanel report noted, however, that while the series of events that must occur for the wild plant to acquire a selective advantage is rather improbable, such a series of events is not impossible. To address this possibility, the Agency is offering an alternative option that is a more limited exemption of vcp-mediated resistance coat proteins. For this alternative option, the Agency has defined a set of criteria and a process that would be used to identify those viral coat protein/plant combinations that have the greatest potential to outcross to wild, free-living relatives and thus have the possibility to endow these wild relatives with a competitive advantage. Viral coat proteins that potentially could be outcrossed would be subject to regulation. Those viral coat protein/plant combinations with a lesser or no probability of outcrossing and thus having a lesser or no probability of resulting in selective advantage would be exempt from regulation. An example of the latter situation would occur when a plant has no wild relatives in the United States or, if it has such relatives, cannot exchange genetic material with any of them. Under such circumstances, there is no opportunity for selective advantage through acquisition of the gene encoding the viral coat protein to occur in the wild relative since successful genetic exchange would not occur. It should be noted that neither of the exemptions described by Option 1 nor Option 2 for viral coat proteins extends to other methods used to create viral resistance in plants, such as the introduction of the gene encoding for RNA replicase or the introduction of genes encoding for satellite RNA (supernumary RNA with essentially no sequence similarity with the host virus) into plants. EPA does not believe it should exempt satellite RNA since single nucleotide base changes have been shown to significantly alter the characteristics of satellite RNAs including turning a nonnecrogenic satellite into a necrogenic satellite. At this point, the Agency is only proposing an exemption for vcp-mediated resistance coat proteins from plant viruses. EPA prefers Option 1 for a number of reasons. EPA believes that the use of vcp-mediated resistance represents little potential for adversely affecting nontarget organisms and has a low potential for other environmental risks even in the absence of any regulatory oversight under FIFRA. In addition, vcp-mediated resistance is associated with potential environmental benefits such as decreased use of chemical pesticides and economic benefits to farmers and society because it represents a means of controlling losses to viral disease in the absence of effective alternative methods to control viral infection. Option 1 represents a clearer regulatory line than Option 2 in terms of which plant-pesticides will be regulated under FIFRA. Option 1 is more consistent with the approach taken for plant- pesticides under FFDCA. Option 1 allows the Agency to focus on plant- pesticides posing higher potential risks. In addition, under the Plant Pest Act, USDA/APHIS addresses the potential for selective advantage among wild plants in its review of plants genetically engineered to produce viral coat proteins. At the January 21, 1994 joint SAP/Biotechnology Science Advisory Committee (BSAC) meeting (see Unit VI of this preamble), the alternative option (Option 2) for the exemption of viral coat proteins was discussed. The joint Subpanel agreed that Option 2 created a process to address the possibility of selective advantage being acquired by a wild relative through outcrossing of the vcp-mediated resistance coat protein gene from the modified crop plant. However, the joint Subpanel did not believe that there was a high enough level of concern to warrant the inclusion of this option. The report of the January 21, 1994 meeting summarizes that: (1) Wild relatives are not found growing near many of the important crop plants grown in the United States; (2) criteria 2 and 3 of the alternative option address extremely rare situations, the existence of which would be very difficult to completely disprove; (3) the potential for increasing the ability of wild relatives to resist viral infection is likely to be beneficial because it could lead to a reduction of the reservoir for plant viruses; and (4) the use of vcp-mediated resistance is more ``environmentally friendly'' than the application of chemical pesticides to control virus vectors. The Agency's preferred option would be to completely exempt vcp- mediated coat proteins from FIFRA regulation. Because of the potential benefits and the low probability of risks from the use of vcp-mediated resistance coat proteins in plants, EPA believes they warrant exemption under FIFRA 25(b) as being ``of a character that is not necessary to be subject to the Act.'' In addition, USDA/APHIS's review of field testing of plants genetically engineered to produce vcp-mediated resistance proteins addresses the possibility that the use of vcp-mediated coat proteins may create some potential for a selective advantage to be acquired by wild plants as well as the possibility of creating new viruses through recombination and/or transencapsidation. EPA is aware that, in addition to viral coat proteins, there are viral components such as viral movement proteins and viral replicase that are being tested for virus resistance strategies in plants. Many of the risk issues considered by EPA for viral coat proteins may be similar to those most likely to be addressed when examining the risks that could potentially be associated with the use of other viral components. USDA/APHIS's review of plants genetically engineered to produce viral coat proteins addresses such potential risks. EPA is committed to minimizing duplicative review of products between Federal agencies and is also committed to developing an appropriate regulatory approach for biologically-based pesticides in general, potentially including pesticides based on viral components produced in plants. EPA would tailor its regulatory procedures according to the biological characteristics of these products. These procedures could, for example, include expedited procedures for registration, the development of performance-based criteria for exemptions, and specific product exemptions. For example, the exemption of plant-pesticides that ``primarily affect the plant'' could be extended in the future, through the inclusion of an additional criterion, to include viral components that are used in viral resistance strategies in plants when they affect the plant so that the viral pest cannot invade the plant. VI. External Review In developing its approach to regulating plant-pesticides, EPA has requested the advice of two scientific advisory committees at three meetings. On December 19, 1992, pursuant to section 25 of FIFRA, a Subpanel of the FIFRA SAP was convened to review a draft policy statement on plant-pesticides and respond to a series of scientific questions posed by the Agency primarily on EPA's approach under FIFRA. On July 13, 1993, a Subcommittee of the EPA BSAC was convened to address a series of scientific questions primarily on EPA's approach under FFDCA. On January 21, 1994, a joint meeting of a SAP/BSAC Subpanel on plant-pesticides was held. The issues raised at these meetings are discussed below, together with the Agency's response. (Full reports from these meetings are available in the public docket.) A. Substances New to the Plant Questions on how best to describe ``substances that are new to the plant'' were posed at all three science advisory meetings. At its December 1992 meeting, the FIFRA SAP Subpanel was asked whether the taxonomic demarcation of ``genus'' was appropriate, or whether some other demarcation would be more appropriate. The Subpanel expressed concern over an exemption based on a taxonomic definition and suggested the Agency evaluate a series of considerations involving the potential for quantitative and qualitative differences in exposure to a plant- pesticide. The SAP Subpanel suggested that the Agency would ``need to create a workable balance between effective regulatory oversight and encouragement of the development of plant-produced pesticides.'' At its July 13, 1993 meeting, the BSAC Subcommittee addressed a related issue with regard to the regulation of plant-pesticides under the FFDCA and human dietary exposures to plant pesticides. Included in questions to the Subcommittee were queries on the availability of information on current levels of exposure in the diet to plant-pesticides in raw agricultural commodities and on which plant- pesticides might be of concern should their levels be significantly increased. The BSAC Subcommittee in their report stated that no formal, complete data base for such information exists. Rather most of this knowledge is part of breeders' experience, with breeders depending primarily on familiarity with food crops (e.g., knowledge of which crop plants have the ability to produce which toxicants) to ensure consumers are not exposed to deleterious levels of such substances. In general, little information exists on the range of levels of plant-pesticides in plants, including ranges within the most studied grouping, food plants. The mechanisms through which plants display resistance to pests, moreover, have not been well worked out. Based on experience, however, the BSAC Subcommittee suggested EPA consider a scheme based on sexual compatibility to identify those groupings wherein plant-pesticides might present new and novel dietary exposures and those that would not. The use of sexual compatibility and/or taxonomy as a standard for the potential for significantly different environmental exposures was discussed at the January 21, 1994, joint SAP/BSAC Subpanel meeting. The panel members were supplied with the reports of the previous meetings and drafts of proposals analyzing the strengths and weaknesses of approaches based on sexual compatibility and/or taxonomy. In response to the question of whether plants in a sexually compatible population are likely to share substances or traits, the joint Subpanel agreed that sexually compatible plants are more likely to have a common constitution than unrelated plants and thus movement of genetic material between sexually compatible plants is less likely to lead to novel exposures. Natural hybridization and selection have produced groups of plants which have a common gene pool. Generations of artificial hybridization to produce improved cultivated plants have tended to increase the extent of relatedness among elements of a broader segment of the natural diversity. In addition, modern techniques of genetic mapping have revealed the presence of genetic loci in cultivated plants that previously were considered to be present only in the wild species. In regard to the correlation of the concept of ``genus'' with significantly different environmental exposures, the panel noted that the taxonomic classification of a genus and the measure of sexual compatibility are closely interrelated. Sexual compatibility tends to promote genetic interchange and this interchange leads to populations of plants more like each other than like groups that have been sexually isolated. Because plants in the same genus likely have common ancestors that at some period in their evolution were sexually compatible, plants in the same genus are more apt to be sexually compatible with each other than with plants from other genera. Some barriers to sexual compatibility exist between species in the same genus even though the species are similar taxonomically. However, many of these sexual barriers can be overcome through the use of wide cross techniques by breeders. The report of the January 21, 1994, joint SAP/BSAC Subpanel meeting, indicates that the joint Subpanel agrees that basing an exemption on both the concept of sexual compatibility and the concept of taxonomy should restrict the occurrence of significantly different exposures and finds that Option 3 is a reasonable approach for agricultural plants. However, the joint Subpanel questioned whether an assumption of low probability of novel exposures can be extended to wild or semi-wild plants. For these types of plants, the genus standard ``in particular,'' may result in the exemption from regulation of plant-pesticides that may present novel exposures. The Agency also included a question, at the January 21, 1994, joint BSAC/SAP meeting, concerning an approach using a criterion based on the process used to modify the plant, e.g., recombinant DNA methodologies. As described in the report of the joint BSAC/SAP Subpanel meeting, if the Agency were to use this approach, it would first exempt plant- pesticides developed through techniques other than those of modern biotechnology from its regulatory scope. For those plant-pesticides that are not exempted because they were developed through techniques of modern biotechnology, the exemptions proposed by the Agency would apply (i.e., the exemption based on plants' relatedness and the exemption of plant-pesticides that act by ``primarily affecting the plant''; see Units V.A. and V.B. of this preamble). The joint Subpanel supported the inclusion of an option using a criterion based on methodologies such as rDNA as a rational approach to making the first cut as to which plant-pesticides would be regulated. However, the joint Subpanel cautioned that further exemptions such as those proposed by EPA should be used in conjunction with the criterion based on methodology. In addition, the joint Subpanel recommended that the Agency define methodologies in a way that clearly delineates to the scientific community and the public what is and is not included in the regulatory scope, based on current state-of-the science. EPA Response: The Agency has chosen to propose to use under both statutes, an approach based on sexual compatibility. First, this approach would exempt under both FIFRA and FFDCA, plant-pesticides having a high probability of being derived from plants having high numbers of genes in common. Under such circumstances, the likelihood of new or novel exposures both to the environment and in terms of human consumption is low. Second, use of the standard of sexual compatibility is the preferred option under both FIFRA and FFDCA and would allow EPA to use its authorities under FIFRA and FFDCA in concert to regulate plant- pesticides, and thus to utilize, to the extent possible in light of the different statutory standards, similar approaches to oversight under each of the two statutes. Third, the Agency believes that its proposed approach would be consistent with the December 1992 SAP Supbanel's concern that EPA ``. . . create a workable balance between effective regulatory oversight and encouragement of the development of plant-produced pesticides.'' Under the preferred approach, novel exposures are not likely to occur with plant-pesticides exchanged between plants that are sexually compatible (See also Unit V. of this preamble for additional discussion). With regard to the advice of the January 21, 1994, joint SAP/BSAC Subpanel concerning the use of a process-based criterion in the scope, if the Agency were to use this approach, plant-pesticides developed through techniques other than those involving in vitro manipulation of genetic material would be exempt. In order to meet the recommendations of the joint Subpanel, the Agency would define this category of plant- pesticides in the following way: The genetic material that encodes for the pesticidal substance or leads to the production of the pesticidal substance is extracted from an organism and introduced into the genome of the recipient plant or is synthesized in vitro and introduced into the genome of the recipient plant. The exemptions proposed by the Agency in Unit V. of this preamble would be used in concert with this criterion. The Agency believes this approach would meet the recommendations of the SAP/BSAC joint Subpanel. The Agency is soliciting comment on this approach (see Unit VII.A. of this preamble). B. Plant-pesticides That Act Primarily by Affecting the Plant The SAP Subpanel at its December 1992 meeting considered whether EPA's language clearly and sufficiently identified plant resistance mechanisms that do not involve substances whose mode of action produces a direct toxic effect on the pest. The SAP Subpanel stated that for the most part the language EPA was proposing was clear and appropriately identified plant resistance mechanisms whose mode of action was not directly toxic. The Subpanel noted, however, that the issue of resistance to toxins produced by the pests was not addressed by that language. The Subpanel recommended insertion of the following statement into EPA's proposed language: ``Acts in the host plant to produce target(s) of the toxin that are resistant to the toxin's deleterious action.'' EPA Response: EPA accepted this recommendation and modified the language of its approach to incorporate the issue of resistance to toxins. C. Viral Coat Proteins The December 18, 1992, SAP Subpanel meeting and the January 21, 1994, joint SAP/BSAC Subpanel meeting addressed the use of viral coat protein genes to modify plants to protect the plant from damage from viral infection. In the discussion at the December 18, 1992, SAP Subpanel meeting, several risk considerations were identified and the probability of occurrence of each addressed in the SAP Subpanel report. The SAP Subpanel report stated that the probability of occurrence of the risks examined is very low. The January 21, 1994, joint SAP/BSAC Subpanel meeting discussed the alternative option for the exemption of viral coat proteins from FIFRA regulation. The joint Subpanel did not believe that the potential risks associated with the use of vcp- mediated resistance coat proteins warranted inclusion of the alternative option. Unit IV.C.3. of this document describes how the SAP and joint SAP/BSAC discussion of vcp-mediated resistance viral coat proteins supplements and influences EPA's analysis. EPA Response: EPA agrees that the probability of risks from the introduction of viral coat protein genes into plant genomes is low, and as its preferred option proposes to exempt these plant-pesticides from FIFRA oversight. Because of public comments received at the December 18, 1992, SAP Subpanel meeting and the January 21, 1994, joint SAP/BSAC meeting, however, concerning viral coat protein and selective advantage to wild relatives of managed plants, EPA is offering for comment in this proposal the alternative approach to viral coat proteins to allow the fullest discussion possible. D. U.S. Congress and U.S. Department of Agriculture In accordance with FIFRA section 25, a draft of this proposed regulation and a draft of the statement of policy published elsewhere in today's issue of the Federal Register entitled ``Proposed Policy; Plant-pesticides Subject to the Federal Insecticide, Fungicide, and Rodenticide Act and the Federal Food, Drug, and Cosmetic Act'' (proposed policy statement) was submitted in June 1994, to the U.S. Congress and USDA. USDA provided written comments on these two drafts on August 18, 1994. These comments are discussed below together with EPA's response. 1. USDA suggests that the exemption EPA is proposing under FIFRA for viral coat proteins should be extended to include all plant viral proteins used in viral resistance strategies and the viral genetic sequences that encode them (including antisense constructs). EPA response: While EPA does not believe that, at this time, it can exempt all viral components from regulation under FIFRA it has requested comment on such an exemption. EPA is committed to minimizing duplicative review and would develop a coordinated approach with USDA for viral-based products other than viral coat proteins. As the experience base grows for these products, the two agencies can develop a regulatory course that is mutually acceptable. These procedures could, for example, include expedited procedures for registration, the development of performance-based criteria for exemptions, and specific product exemptions. 2. USDA suggested that ambiguity exists in the use of the term ``user'' in the discussion on informational labeling for plant- pesticides in the proposed policy statement. EPA Response: EPA agrees that this discussion in the proposed policy statement may be ambiguous and proposes to replace the term ``user'' with the term ``farmer and grower.'' 3. USDA noted that EPA's exemption based on the premise that plant- pesticides derived from sexually compatible plants would not result in new environmental exposures does not take into account that similar or equivalent genes can be found in plants that are not sexually compatible. EPA's Response: EPA recognizes that plant defense compounds found in plants that are not sexually compatible, or in other organisms such as microorganisms, can be structurally and functionally equivalent to compounds found in the recipient plant or in a plant sexually compatible with the recipient plant. The Agency is willing to consider development of procedures and criteria for these plant-pesticides. A discussion of these procedures and criteria can be found in the Request for Comment unit, Unit VII., of this preamble. 4. Although not included in USDA's written comments, USDA suggested, in a discussion at an August 18, 1994 meeting between USDA and EPA representatives, some clarifications in the discussion on plant regulators and plant hormones in the proposed policy statement. USDA indicated that there was some ambiguity as to how EPA would regulate plant hormones under FIFRA. EPA Response: EPA agrees that the plant regulator discussion may lead to some confusion as to how EPA would regulate plant hormones. EPA has agreed to include a discussion in the section on plant regulators in the proposed policy statement that would more fully describe the status of these plant-pesticides in relation to the proposed exemption of plant-pesticides derived from sexually compatible plants or under the proposed exemption of plant-pesticides that ``. . .primarily affect the plant. . .'' (see Unit IV.D.in the proposal published elsewhere in today's issue of the Federal Register entitled ``Plant-pesticides Subject to the Federal Insecticide, Fungicide, and Rodenticide Act; Proposed Rule''). VII. Request for Comment The Agency requests comments on the proposed exemptions of plant- pesticides under FIFRA. A. Exemption of Plant-pesticides Derived from Closely Related Plants 1. Three options. EPA requests comment on whether the Agency has appropriately identified in this proposed exemption (see Unit V.A. of this preamble) those plant-pesticides that are not likely to result in significantly different environmental exposures. EPA requests comment on its three options, specifically as to whether the options appropriately identify plant-pesticides that would not result in significantly different exposures to nontarget organisms and whether the language the Agency uses in the options clearly circumscribes the appropriate groupings. EPA requests comments on which option is most appropriate and why. 2. Criterion based on process. With regard to an exemption criterion based on the process used to modify the plant, the Agency is soliciting comment on the joint BSAC/SAP Subpanel advice and the utility of an approach based on that advice (see Unit VI. of this preamble). EPA also requests comment on whether the group of plant- pesticides that would be regulated under this approach would be equivalent to the group of plant-pesticides that would be regulated under Options 1, 2, or 3. 3. Equivalent plant-pesticides. As described in Unit V.A.6. of this preamble, EPA is considering the development of procedures and criteria for how EPA can exempt a plant-pesticide if a producer can provide evidence that the plant-pesticide is structurally and functionally equivalent to a plant-pesticide found in a recipient plant or in a plant sexually compatible with the recipient plant. To effect such rulemaking, the Agency would need to meet statutory standards under FIFRA. In the instance of plant-pesticides, EPA would need, for example, to determine whether a plant-pesticide is indeed structurally and functionally equivalent to a plant-pesticide that has been exempted. Under such a rulemaking effort, a producer would provide information to the Agency showing that a plant-pesticide meets the standard for exemption under FIFRA. The Agency would respond, within a limited period of time, to the producer as to whether the plant- pesticide meets that standard. The Agency envisions that producers would have a fairly high degree of latitude in types of specific data that could be used to demonstrate that a plant-pesticide meets the standard for exemption. The Agency is requesting comment on this framework for the exemption rulemakings. In particular, the Agency is soliciting comment and information on whether to incorporate specific data requirements/ methodologies into exemption criteria and on appropriate time-frames for the Agency determinations. The main challenge for EPA in engaging in such future rulemakings will be to develop criteria that can be used to create a standard for what constitutes equivalency. There are a number of different approaches that EPA believes it could utilize. The following discussion describes these approaches and some of the strengths and weaknesses of these options. The Agency requests comment on these approaches and solicits suggestions on additional factors that the Agency should weigh in the development of criteria for equivalency. In developing criteria for exempting a plant-pesticide from FIFRA, the first consideration for EPA is what parameters, in general, are good measurements for equivalency of function. The next consideration for the Agency in the development of criteria for creating exemptions is to examine these parameters in light of what is known concerning the characteristics of plant defense mechanisms. Turning first to the general parameters, some examples of the types of parameters that the Agency could use in developing criteria for proteinaceous substances are amino acid sequence homology, posttranslational processing, structure, stability, receptor/ligand specificity, and substrate specificity. For nonproteinaceous substances, equivalence in chemical composition and structure are additional examples of parameters that could be used as the basis for developing criteria. Any measures of equivalence that the Agency chooses to adopt should be applicable to particular plant-pesticides that may operate by a variety of mechanisms. The Agency requests comment on how evidence of structurally homology for proteinaceous defense compounds could be used in the future as reliable predictors of functional homology. Would it be more appropriate to develop an approach that does not rely soley on percent amino acid sequence homology but also incorporates the identification of conserved and variable amino acid sequences? For example, it is postulated that some disease resistance genes encode transmembrane receptors. Might sequences such as those involved in transmembrane interactions then be identified to provide additional assessment of equivalent function? A number of enzymes such as glucanase, chitinase, and proteinase inhibitors are also thought to be involved in plant defense responses. The question then arises as to whether a chitinase from, for example, tobacco or a microorganism is equivalent to a chitinase found in a plant sexually compatible with the recipient plant. As in the previous example, amino acid sequence homology could also assist in establishing equivalency for these enzymes. However, as with the previous example, the question of how much homology is sufficient remains. Would a better measurement be to use stability, substrate specificity, Km, and Vmax? Should these parameters be used in conjunction with homology? Nonproteinaceous compounds such as phenolics and phytoalexins are another class of plant defense compounds. For nonproteinaceous compounds structure/activity comparisons can be used to determine functional equivalence. For example, the presence of specific side chains could be used to establish equivalence. Other parameters such as stability could also be used. The question for the Agency is what amount/combinations of information would be necessary to use as a measure of equivalence.. B. Exemption of Plant-pesticides that Act Primarily by Affecting the Plant With regard to its exemption from FIFRA requirements of ``plant- pesticides that act primarily by affecting the plant,'' EPA requests comment on whether this exemption appropriately focuses the Agency's regulatory attention on the plant-pesticides likely to present higher levels of hazard. The Agency also requests comment on whether the language defining this exemption is sufficiently clear and inclusive to identify plant-pesticides that act through nontoxic modes of action. The Agency is considering whether to extend this exemption to include substances such as plant hormones because they primarily affect the plant and do not have a directly toxic mechanism of action toward the target pest. The Agency is requesting comment as to whether it would be more appropriate to specifically exempt plant hormones as a category or to include in this exemption a performance-based criterion based on a description of the characteristics and/or mechanism of action of hormones (see Unit V.B. of this preamble). C. Exemption of Coat Proteins from Plant Viruses EPA is also proposing to exempt from FIFRA regulation, coat proteins from plant viruses when the coat proteins are produced in plants. EPA has proposed two options for this exemption with Option 1 presented in the proposed regulatory text. EPA is requesting comment on the appropriateness and clarity of the two options presented in this proposal. EPA is also requesting comment on: (1) The potential for the recipient crop plant producing the viral coat protein to become a weed; (2) the potential for increased competitive advantage of wild relatives in their native habitat after cross hybridization with a crop plant producing a viral coat protein; and (3) the potential for a viral coat protein gene to recombine with infecting viruses to extend host range or create new virus diseases. EPA is considering whether to propose in the future, an exemption of viral components, other than viral coat proteins, used in viral resistance strategies in plants. This exemption would include performance-based criteria that would be used by EPA to determine if a viral component would be exempt from regulation. EPA is requesting comment on whether such an exemption would be appropriate and is requesting comment on criteria that could be used to construct this exemption. D. Substantiation of Claims for Confidential Information EPA requests comment on the proposed requirement (Sec. 174.9 of the regulatory text) that any claim of confidentiality must be substantiated at the time the claim is made. Specifically, EPA seeks comment on how to achieve the best balance between the burden on industry to provide substantiation before public disclosure becomes an active issue (e.g., in preparation for FIFRA Science Advisory Panel meetings) and the regulated community's desire to receive timely responses on submissions. This balance must take into consideration the needs of pesticide developers to protect information they believe to be critical to maintaining their competitiveness and the public's need for access to information related to potential environmental or human health effects early enough in the review process to provide informed comment before EPA makes a decision. EPA encourages the development of reduced risk pesticides and believes that, given the Agency's procedural requirements for CBI determinations, without up front substantiation, timely responses to subsmissions would be difficult when it becomes necessary to resolve the issue of CBI before a decision can be made. VIII. Economic Analysis The regulatory impact analysis (RIA) evaluates the costs and benefits of amending EPA's regulations to allow for the regulation or exemption of specific types of plant-pesticides under FIFRA (40 CFR 152.20 and 40 CFR part 174) and is intended to meet the requirements for a RIA as established by Executive Order No. 12866, the Regulatory Flexibility Act, and section 25 of FIFRA. The RIA presents the alternative regulatory options and the costs that were considered by the Agency including two options that were considered by the Agency but not included in this proposal. Four possible approaches to the regulation of plant-pesticides under FIFRA were evaluated in the RIA that allowed for varying degrees of regulatory coverage. RIA Option 1 is the most limited alternative in regulatory scope. RIA Option 2 represents EPA's proposed, and preferred, regulatory scope and is broader in coverage than RIA Option 1. In addition to those plant-pesticides regulated under RIA Option 2, RIA Option 3's scope would include viral coat proteins used as plant- pesticides. Finally, under RIA Option 4, all plant-pesticides, including those that result from traditional plant breeding, would be subject to the requirements of FIFRA. The costs of implementing the four options presented in Unit IV.A. of this preamble are comparable to each other and correspond to RIA Option 2. The costs for any of the four options presented in Unit IV.A. are substantially lower than RIA Option 4. Generally, costs will depend on whether the Agency exempts a plant- pesticide or whether it requires a registration. The costs of regulating plant-pesticides are dependent upon the data needed for the registration of the particular types of plant-pesticides. Data needs are irrelevant for exempted plant-pesticides. For regulated plant- pesticides, data needs will vary according to the gene product of the plant-pesticide and the recipient crop. Aggregate incremental compliance costs to the industry over a 10- year period under regulatory (RIA) Option 1 are estimated to range from $53,700 in the first year of implementation to $2.6 million in the 10th year of implementation, with an average annual revenue requirement (ARR) of $1.2 million. Under EPA's proposed scope (RIA Option 2), aggregate incremental compliance costs are predicted to range from $53,700 in year 1 to $3.1 million in year 10, with an ARR of $1.6 million. Aggregate incremental compliance costs for RIA Option 3 are estimated at nearly $741,100 in the first year of implementation and $5.1 million in the 10th year, with an ARR of $2.9 million. Finally, under RIA Option 4's broad regulatory scope, aggregate incremental compliance costs are projected to range from $76.6 million in year 1 to $81 million in year 10, with an ARR of $79 million. Costs were also estimated for the labor burden that would result from EPA staff preforming various activities associated with the registration of plant-pesticides. Some of these activities may include the establishment of the docket, internal reviews, requests for additional information, and consultations with applicants. The cost for the Agency to perform these activities under RIA Option 1 is estimated to range from nearly $40,000 in year 1 to approximately $259,000 in year 10. Under EPA's proposed regulatory scope, RIA Option 2, annual labor burden costs range from approximately $40,000 in the first year to $391,000 10 years after a final rule is promulgated. For RIA Option 3, EPA costs are estimated to range between $123,000 in year 1 to $640,000 in year 10. Under the broad regulatory scope of RIA Option 4, EPA's labor costs are predicted to range between $14.7 million in year 1 to $15.2 million in year 10. Labor burden cost estimates vary by year, due to the number and type of plant-pesticide submissions the Agency is predicted to receive. The aggregate cost to society of the proposed plant-pesticide regulation is the sum of the total costs to industry, plus the total costs to the Agency to implement the proposed rule. After calculating aggregate societal costs, they were discounted to allow for the time value of money and to determine a constant level annual cost. The annual societal revenue requirement over the 10-year period of analysis was estimated at nearly $1.4 million under RIA Option 1, $1.8 million under RIA Option 2, $3.3 million under RIA Option 3, and $93.7 million under RIA Option 4. Primarily affected by this proposed regulation will be those companies involved with agricultural biotechnology that have been identified as presently developing and testing plant-pesticides. While agricultural biotechnology is currently in its infancy with 1993 sales estimated at less than 2 percent of total biotechnology sales, future sales are forecasted to grow at an average annual rate of 33 percent to the year 2003. Firms developing biotechnology products are quite diverse and include large, multinational corporations, biotechnology companies (both large and very small), chemical companies, and seed companies. The impacts of EPA regulation of plant-pesticides to this growing market sector will not be all negative. Companies involved with agricultural biotechnology have asked for plant-pesticide regulations and they stand to benefit tremendously from this proposed regulation. The proposed rule will generate a wide range of benefits for the public, the firms involved with agricultural biotechnology, the environment, nontarget organisms, and states. Registrants of plant- pesticides should benefit from the resolution of uncertainty regarding regulatory issues. With the promulgation of the proposed regulation, firms developing and testing plant-pesticides can plan ahead for timely product development and commercialization which should, in turn, attract investors to the agricultural biotechnology sector. The environment will benefit from safety measures that will protect against unintended environmental effects of accidental and deliberate releases of genetically engineered organisms. Nontarget organisms, including endangered species, will benefit from a registration process that will carefully consider the potential effects that certain plant-pesticides may have upon them. Finally, states will benefit by having a set of standardized Federal regulations that will be more easily conveyed, interpreted, and enforced. Many states may also benefit by not having to establish their own set of agricultural biotechnology regulations. Adverse economic impacts from the implementation of the proposed plant-pesticide regulation are not expected under EPA's proposed scope (RIA Option 2). Due to the lack of detailed financial information on those firms that are currently developing and testing plant-pesticides, the conclusion of ``no adverse economic impacts'' was based on public and proprietary information provided to EPA by industry financial advisory groups, biotechnology associations, university biotechnology specialists, and small biotechnology firms. IX. Public Record EPA has established a public record for this rulemaking (docket control number OPP-300369). The record includes all information considered by EPA in developing this proposed rule. The record now includes the following items: 1. Reports of all SAP and BSAC meeting pertaining to this proposed rule. 2. Support documents and reports, including: (a) EPA issue paper. FIFRA: Benefit and environmental risk considerations for inherent plant-pesticides. (b) EPA issue paper. Issues associated with the regulation of viral coat proteins under FIFRA and FFDCA. 3. Published literature that is cited in this document. 4. The Regulatory Impact Analysis for this rule. 5. Records of communications between EPA personnel and persons outside EPA pertaining to the development of this proposed rule. (This does not include any inter- or intra-agency memoranda, unless specifically noted in the Index of this docket.) X. References (1) EPA issue paper. FIFRA: Benefit and environmental risk considerations for inherent plant-pesticides. (2) EPA issue paper. Issues associated with the regulation of viral coat proteins under FIFRA and FFDCA. (3) Klaasen, C.D., M.O. Amdur, and J.D. Doull. 1986. Casarett and Doull's Toxicology: The Basic Science of Poisons. Chapter 2. Third Edition. Macmillan Publishing Company, New York. (4) Lamb, C.J., J.A. Ryals, E.R. Ward, and R.A. Dixon. 1992. Emerging strategies for enhancing crop resistance to microbial pathogens. Bio/Technology. 10:1436-1445. (5) Matthews, R.E.F. 1981. Plant Virology. Chap. 17. Second edition, Academic Press, New York. (6) Tolin, S.A. 1991. Persistence, establishment, and mitigation of phytopathogenic viruses. In: Risk Assessment in Genetic Engineering. Edited by M.A. Levin and H.S. Strauss. McGraw Hill, Inc., New York. pp. 140-161. XI. Regulatory Assessment Requirements A. Executive Order 12866 Under Executive Order 12866 (58 FR 51735, October 4, 1993), the Agency must determine whether the proposed regulatory action is ``significant'' and therefore subject to review by the Office of Management and Budget (OMB) and the requirements of the Executive Order. Under section 3(f), the Order defines a ``significant regulatory action'' as an action that is likely to result in a rule (1) Having an annual effect on the economy of $100 million or more, or adversely and materially affecting a sector of the economy, productivity, competition, jobs, the environment, public health or safety, or State, local, or tribal governments or communities (also referred to as ``economically significant''); (2) creating serious inconsistency or otherwise interfering with an action taken or planned by another agency; (3) materially altering the budgetary impacts of entitlement, grants, user fees, or loan programs or the rights and obligations of recipients thereof; or (4) raising novel legal or policy issues arising out of legal mandates, the President's priorities, or the principles set forth in this Executive Order. Pursuant to the terms of this Executive Order, EPA has determined that this proposed rule is a ``significant regulatory action'' because it raises novel policy issues arising out of FIFRA legal mandates. Thus, this proposal will be submitted to OMB for review, and any comments or changes made in response to OMB suggestions or recommendations, are documented in the public record. B. Regulatory Flexibility Act This proposed rule was reviewed under the provisions of section 3(a) Regulatory Flexibility Act (RFA) [5 U.S.C. 605(b)]. The RFA requires that agencies take special note of the impact of proposed regulations on small entities. Analysis requirements under the RFA can and should be combined with the analysis required under Executive Order 12866. The regulatory flexibility analysis of this proposed regulation for plant-pesticides on small entities is demonstrated within the structuring of the four regulatory options proposed. These options were considered after extensive evaluations of the benefit/risk tradeoffs between option cost and risk reduction provided. The Agency has structured the resulting options from a narrow regulatory scope (RIA Option 1) to a broad regulatory scope (RIA Option 4) and, as such, has conducted an ``inherent'' sensitivity analysis for small firms likely to be affected by this proposed regulation. The Agency has determined that the tradeoffs between the benefits and risks of the proposed regulation are optimized under RIA Option 2, EPA's proposed scope. C. Paperwork Reduction Act Paperwork Reduction Act The information collection requirements in this proposed rule have been submitted for approval to the Office of Management and Budget (OMB) under the Paperwork Reduction Act, 44 U.S.C. 3501 et seq. An Information Collection Request document has been prepared by EPA (ICR No. 1693.01) and a copy may be obtained from Sandy Farmer, Information Policy Branch, (Mail Code 2136), Environmental Protection Agency, 401 M St., SW., Washington, DC 20460, or by calling (202) 260-2740. This collection of information has an estimated reporting burden averaging 1,143 hours per response and an estimated annual recordkeeping burden averaging 74 hours per respondent. These estimates include time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding the burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Chief, Information Policy Branch, (Mail Code 2136), Environmental Protection Agency, 401 M St., SW., Washington, DC 20460; and to the Office of Information and Regulatory Affairs, Office of Management and Budget, Washington, DC 20503, marked ``Attention: Desk Officer for EPA.'' The final rule will respond to any OMB or public comments on the information collection requirements contained in this proposal. List of Subjects in Parts 152 and 174 Environmental protection, Biotechnology pesticides, Pesticides and pests, Plants, Plant-pesticides, Reporting and recordkeeping requirements. Dated: November 15, 1994. Carol M. Browner, Administrator. Therefore, it is proposed that 40 CFR Chapter I be amended as follows: PART 152--[AMENDED] 1. In part 152: a. The authority citation for part 152 would continue to read as follows: Authority: 7 U.S.C. 136-136y; subpart U is also issued under 31 U.S.C. 9701. b. In Sec. 152.1, by designating existing text as introductory text and adding paragraphs (a) and (b) to read as follows: Sec. 152.1 Scope. * * * * * (a) For procedures, requirements and criteria applicable to plant- pesticides, refer to part 174 of this chapter. (b) [Reserved] c. In Sec. 152.3, by removing all alphabetic paragraph designations and alphabetically inserting the following definitions to read as follows: Sec. 152.3 Definitions. * * * * * Genetic material necessary for the production means: (1) Genetic material that encodes for a pesticidal substance or leads to the production of a pesticidal substance. (2) Regulatory regions. It does not include noncoding, nonexpressed nucleotide sequences. * * * * * Living plant means a plant that is alive, including periods of dormancy, and all viable plant parts/organs involved in the plant's life cycle. * * * * * Noncoding, nonexpressed nucleotide sequences means the nucleotide sequences are not transcribed and are not involved in gene expression. Examples of noncoding, nonexpressed nucleotide sequences include linkers, adapters, homopolymers, and sequences of restriction enzyme recognition sites. * * * * * Plant-pesticide means a pesticidal substance that is produced in a living plant and the genetic material necessary for the production of the substance, where the substance is intended for use in the living plant. Regulatory region means genetic material that controls the expression of the genetic material that encodes for a pesticidal substance or leads to the production of a pesticidal substance. Examples of regulatory regions include promoters, enhancers, and terminators. * * * * * d. In Sec. 152.20, by revising paragraph (a)(1) and adding paragraph (a)(4) to read as follows: Sec. 152.20 Exemptions for pesticides regulated by another Federal agency. * * * * * (a) * * * (1) Except as provided by paragraphs (a)(3) and (a)(4) of this section, all biological control agents are exempt from FIFRA requirements. * * * * * (4) All plants intended for use as biological control agents and any portion thereof, except plant-pesticides, are exempt from the requirements of FIFRA. Plant-pesticides are addressed in part 174, subpart A, of this chapter. * * * * * 2. By adding part 174 to read as follows: PART 174--PROCEDURES AND REQUIREMENTS FOR PLANT-PESTICIDES Subpart A--General Provisions Sec. 174.1 Scope and purpose. 174.3 Definitions. 174.5 Scope of coverage. 174.7 Submission of information regarding potential unreasonable adverse effects. 174.9 Confidential business information claims for plant- pesticide submissions. Subpart B--[Reserved] Authority: 7 U.S.C. 136-136y and 21 U.S.C. 346a and 371. Subpart A--General Provisions Sec. 174.1 Scope and purpose. Pesticidal substances produced in plants are pesticides as defined in FIFRA section 2. The characteristics of these pesticides such as their production and use in plants, their biological properties, and their ability to spread and increase in quantity in the environment distinguishes them from traditional, chemical pesticides. Therefore, plant-pesticides are subject to different regulatory requirements and procedures than traditional, chemical pesticides. This part 174 sets forth regulatory requirements, criteria, and procedures applicable to plant-pesticides under FIFRA and FFDCA. Unless otherwise provided by this part, the regulations in parts 152 through 173 and parts 177 through 186 of this chapter, where applicable, apply to plant- pesticides. EPA recognizes the unique nature of plant-pesticides necessitates flexibility in the application of regulations designed for traditional pesticides to plant-pesticides. Sec. 174.3 Definitions. Terms used in this part have the same meaning as in FIFRA. In addition, the following terms have the meaning set forth in this section. Active ingredient, when referring to plant-pesticides only, means a pesticidal substance that is produced in a living plant and the genetic material necessary for the production of the substance, where the substance is intended for use in the living plant. Administrator means the Administrator of the United States Environmental Protection Agency or his/her delegate. Biological control agent means any living organism applied to or introduced into the environment that is intended to function as a pesticide against another organism declared to be a pest by the Administrator. Bridging crosses between plants means the utilization of an intermediate plant in a cross to produce a viable zygote between the intermediate plant and a first plant, in order to cross the plant resulting from that zygote with a third plant that would not otherwise be able to produce viable zygotes from the fusion of its gametes with those of the first plant. The result of the bridging cross is the mixing of genetic material of the first and third plant through the formation of an intermediate zygote. EPA means the United States Environmental Protection Agency unless otherwise specified. FFDCA means the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321 et seq.) FIFRA means the Federal Insecticide, Fungicide, and Rodenticide Act, as amended (7 U.S.C. 136-136y). Genetic material necessary for the production means: (1) Genetic material that encodes for a pesticidal substance or leads to the production of a pesticidal substance. (2) Regulatory regions. It does not include noncoding, nonexpressed nucleotide sequences. Genetic material that encodes for a pesticidal substance or leads to the production of a pesticidal substance does not include regulatory regions or noncoding, nonexpressed nucleotide sequences. Inert ingredient, when referring to plant-pesticides only, means any substance, such as a selectable marker, other than the active ingredient, and the genetic material necessary for the production of the substance, that is intentionally introduced into a living plant along with the active ingredient, where the substance is used to confirm or ensure the presence of the active ingredient. Living plant means a plant that is alive, including periods of dormancy, and all viable plant parts/organs involved in the plant's life cycle. Noncoding, nonexpressed nucleotide sequences means the nucleotide sequences are not transcribed and are not involved in gene expression. Examples of noncoding, nonexpressed nucleotide sequences include linkers, adapters, homopolymers, and sequences of restriction enzyme recognition sites. Pesticide means any substance or mixture of substances intended for preventing, destroying, repelling, or mitigating any pest, or intended for use as a plant regulator, defoliant, or desiccant, other than any article that: (1) Is a new animal drug under FFDCA section 201 (w); or (2) Is an animal drug that has been determined by regulation of the Secretary of Health and Human Services not to be a new animal drug; or (3) Is an animal feed under FFDCA section 201(x) that bears or contains any substances described by Sec. 152.3(s)(1) or (2) of this chapter. Plant-pesticide means a pesticidal substance that is produced in a living plant and the genetic material necessary for the production of the substance, where the substance is intended for use in the living plant. Recipient plant means the plant into which the plant-pesticide is introduced and in which the plant-pesticide is produced. Regulatory region means genetic material that controls the expression of the genetic material that encodes for a pesticidal substance or leads to the production of a pesticidal substance. Examples of regulatory regions include promoters, enhancers, and terminators. Sexually compatible, when referring to plants, means capable of forming a viable zygote through the fusion of two gametes, including the use of bridging crosses or wide crosses between plants. Source means the donor of the genetic material that encodes for a pesticidal substance or leads to the production of a pesticidal substance. Wide crosses between plants means to facilitate the formation of viable zygotes through the use of surgical alteration of the plant pistil, bud pollination, mentor pollen, immunosuppressants, in vitro fertilization, pre- and post-pollination hormone treatments, manipulation of chromosome numbers, embryo culture, or ovary and ovule cultures or any other technique that the Administrator determines meets this definition. Sec. 174.5 Scope of coverage. (a) Plant-pesticides not exempt from the requirements of FIFRA under paragraph (b) of this section are subject to the requirements of FIFRA. (b) All plant-pesticides (both the pesticidal substance and the genetic material necessary for its production) meeting at least one of the following criteria are exempt from the requirements of FIFRA: (1) The genetic material that encodes for a pesticidal substance or leads to the production of a pesticidal substance is derived from plants that are sexually compatible with the recipient plant and has never been derived from a source that is not sexually compatible with the recipient plant. (2) The pesticidal substance acts primarily by affecting the plant so that the target pest is inhibited from attaching to the plant, penetrating the plant, or invading the plant's tissue in at least one of the following ways: (i) The pesticidal substance acts as a structural barrier to attachment of the pest to the host plant, a structural barrier to penetration of the pest into the host plant, or a structural barrier to spread of the pest in the host plant, for example, through the production of wax or lignin, or length of trichomes (plant hairs). (ii) The pesticidal substance acts in the host plant to inactivate or resist toxins or other disease-causing substances produced by the target pest. (iii) The pesticidal substance acts by creating a deficiency of a plant nutrient or chemical component essential for pest growth on/in the host plant. (3) The pesticidal substance is a coat protein from a plant virus. Sec. 174.7 Submission of information regarding potential unreasonable adverse effects. Any person who sells or distributes any plant-pesticide exempt under Sec. 174.5 who obtains any information regarding potential unreasonable adverse effects on human health or the environment must within 30 days of receipt of such information submit the information to EPA, unless the person has actual knowledge that EPA has been adequately informed of such information. Sec. 174.9 Confidential business information claims for plant- pesticide submissions. Although it is strongly recommended that the submitter minimize the amount of data and other information claimed as CBI, a submitter may assert a claim of confidentiality for all or part of the information submitted to EPA in a submission for a plant-pesticide. (See part 2, subpart B, of this chapter.) To assert such a claim, the submitter must comply with the following procedures: (a) Any claim of confidentiality must accompany the information at the time the information is submitted to EPA. Failure to assert a claim at that time will be considered a waiver of confidentiality for the information submitted, and the information may be made available to the public, subject to section 10(g) of FIFRA, with no further notice to the submitter. (b) Any claim of confidentiality must be accompanied, at the time the claim is made, by comments substantiating the claim and explaining why the submitter believes that the information should not be disclosed. The submitter should refer to Sec. 2.205(e)(4) of this chapter for points to address in the substantiation. If such comments are marked confidential when submitted to EPA, they will be treated as such in accordance with Sec. 2.205(c) of this chapter. EPA will consider incomplete all plant-pesticide submissions containing information claimed as CBI that are not accompanied by substantiation, and will suspend the review period of such submissions until the required substantiation is provided. Subpart B--[Reserved] [FR Doc. 94-28822 Filed 11-22-94; 8:45 am] BILLING CODE 6560-50-F