FRIDAY January 22, 1993 Part VII Environmental Protection Agency 40 CFR Part 172 Microbial Pesticides; Experimental Use Permits and Notifications; Proposed Rule (This reprint was prepared from the electronic file that accompanied the original signed documents transmitted to the Office of the Federal Register. This file was certified to be a true copy of the original.) (This document appeared at 58 FR 5877-5902.) Federal Register / Vol. 58, No. 13 / Friday, January 22, 1993 / Proposed Rules ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 172 [OPP - 50668A; FRL - 3887 - 9] [RIN No. 2070 - AB77] Microbial Pesticides; Experimental Use Permits and Notifications AGENCY: Environmental Protection Agency (EPA). ACTION: Proposed rule. SUMMARY: EPA proposes to amend its experimental use permit regulations for pesticides to clarify the circumstances under which an experimental use permit is presumed not to be required. As part of that amendment, EPA proposes to implement a screening procedure that requires notification to the Agency before initiation of small-scale testing of certain microbial pesticides. Three options for defining which microbial pesticides would be subject to the notification requirement are discussed. The Agency will review notifications to assess the potential for adverse impacts on human health or the environment and will then determine whether to require an experimental use permit. This notification scheme would implement provisions of the Agency's policy statement of June 26, 1986, with modifications. DATES: Comments identified by the docket control number [OPP - 50668A] must be received on or before March 23, 1993. ADDRESSES: Submit written comments by mail to: Program Resources Section, Public Response and Program Resources Branch, Field Operations Division (H7506C), Environmental Protection Agency, 401 M St., SW., Washington, DC 20460. In person, bring comments to: Rm. 1132, Crystal Mall 2, 1921 Jefferson Davis Highway, Arlington, VA 22202, FOR FURTHER INFORMATION CONTACT: By mail: Frederick Betz, Acting Chief, Science Analysis and Coordination Staff, Environmental Fate and Effects Division (H7507C), Environmental Protection Agency, 401 M St., SW., Washington, DC 20460. Office location and telephone number: Rm. 1016A, Crystal Mall 2, 1921 Jefferson Davis Highway, Arlington, VA, (703 - 305 - 6307). SUPPLEMENTARY INFORMATION: Electronic Availability: This document is available as an electronic file on The Federal Bulletin Board at 9 a.m. the day of publication in the Federal Register. By modem dial 202 - 512 - 1387 or call 202 - 512 - 1530 for disks or paper copies. This file is available in Postscript, Wordperfect 5.1 and ASCII. Section 5 of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), 7 U.S.C. 136c, and 40 CFR part 172 provide for issuance by the Agency of experimental use permits (EUPs) for the testing of new pesticides or new uses of existing pesticides. Such permits are generally issued for large-scale testing of pesticides. Large-scale tests include any terrestrial application to more than 10 acres of land or any aquatic application to more than 1 surface acre of water. EPA has generally presumed that smaller tests would not require EUPs. However, the Agency believes that small-scale environmental studies with some microbial pesticides may pose sufficiently different risk considerations from conventional pesticides that a closer evaluation at the small-scale testing stage may be warranted. Therefore, the Agency proposes to amend 40 CFR part 172 to require notification before initiation of small-scale testing in the environment of certain microbial pesticides so that the EPA may determine whether these tests should be conducted under an EUP. This proposal would codify the notification provisions of the Agency's policy statement of June 26, 1986 (51 FR 23302), with modifications. Three options for defining the scope of microbial pesticides that would be subject to the notification requirement are discussed. The approach that the Agency is proposing could limit the scope of the notification requirement to a smaller group of microbial pesticides than is currently subject to notification. Until this rulemaking process is complete, however, the Agency will continue to operate under the provisions of the June 26, 1986 policy statement. I. Statutory Authority and Regulatory Background Section 5 of FIFRA provides that any person wishing to test an unregistered pesticide or a registered pesticide for an unregistered use may apply for an EUP. As stated in the preamble proposing the issuance of regulations under section 5 (39 FR 11306, March 27, 1974), ``The purpose behind section 5 is to facilitate the generation of data necessary to support an application for registration under section 3 and yet provide sufficient regulatory control to prevent adverse environmental effects.'' EPA shall issue an EUP only if issuance of such a permit will not cause unreasonable adverse effects on the environment. Similarly, EPA may revoke an existing EUP if it is determined that the terms and conditions of the permit are inadequate to avoid unreasonable adverse effects, 7 U.S.C. 136c; 40 CFR 172.10. Section 2(bb) of FIFRA, 7 U.S.C. 136(bb), defines ``unreasonable adverse effects on the environment'' as ``any unreasonable risk to man or the environment, taking into account the economic, social and environmental costs and benefits of use of [the] pesticide.'' When the EUP regulations, 40 CFR part 172, were originally promulgated (40 FR 18782, April 30, 1975), the Agency recognized that the development of an effective pesticide, culminating in registration, is a multistage process that warrants a scaling in the level of oversight by EPA. Initial testing of a substance is for the purpose of evaluating its value for pesticidal purposes or for determining its toxicity or other properties. This initial testing may include laboratory screening for pesticidal activity, laboratory and greenhouse screening for spectrum of activity, and limited outdoor testing to evaluate pesticidal activity under actual use conditions. Later testing may involve use of larger test plots, often in multiple areas. Both the initial and later testing generate information necessary for registration under section 3 of FIFRA. An EUP issued pursuant to section 5 authorizes limited use of a pesticide on a limited number of acres, under specific and controlled conditions, to develop the necessary data. In proposing the existing regulations governing the issuance of EUPs, EPA stated: The most important environmental consideration in the development of these proposed regulations is the necessity of striking a balance between facilitating -- or, at a minimum, not unduly impeding -- pesticide research and development and protecting against human and environmental injury. Experimental use of pesticides can, of course, pose both human and environmental hazards.... On the other hand, experimental use and testing are essential to the development of new, less hazardous, more effective pesticides, including both chemical and biological agents. In short, there are both risks and benefits associated with experimental use of pesticides (39 FR 11306, March 27, 1974). Given these considerations, EPA set forth procedures that would ``...place experimental programs under reasonable constraints without imposing burdens unrelated to needed protection of human health and the environment'' (39 FR 11306, March 27, 1974). EPA believed that because small-scale tests generally are controlled by the researchers, involve small quantities of pesticides, and are conducted by highly trained personnel, they would pose minimal hazards. Thus, the final regulations included a presumption that EUPs would not be required for most small-scale tests (40 CFR 172.3). However, the regulations also explicitly recognized that a wide variety of testing situations may arise and that a flexible regulatory approach is needed to deal with these situations. EPA retains and exercises the authority to require an EUP for small-scale testing if it determines that such Agency oversight is warranted. The Agency recognizes that there has been a long history of safe use of microbial pesticides. With respect to small-scale testing of most microbial pesticides, the Agency believes that the likelihood that such tests will result in significant adverse impacts on human health or the environment is sufficiently low that Agency oversight is unnecessary. Thus, the Agency believes that, in most instances, small-scale tests (e.g., tests on 10 acres or less of land or on 1 surface acre or less of water) with microbial pesticides should continue to be excluded from the requirement for an EUP. However, since the issuance of the existing EUP regulations, new and different microbial pesticides have been developed that warrant a closer review before being excluded from the EUP requirements. Specifically, the Agency believes that certain microbial pesticides may pose sufficiently different risk considerations from conventional chemical pesticides and other microbial pesticides that screening by EPA through a notification process, before they are used in the environment, is warranted. In amending the EUP regulations, the Agency's goal is to set forth a system that focuses on the characteristics and risks of the product, protects human health and the environment, establishes a screening mechanism that does not unduly impede potentially beneficial research, and is designed to accommodate rapid advances in biotechnology. To achieve this goal, particularly in terms of establishing a screening process that does not unduly impede research, the scope of coverage should clearly describe the kinds of microbial pesticides subject to notification in a way that is uniformly interpretable. In the 1988 amendments to FIFRA, Congress specifically addressed the question of EPA oversight of the use of unregistered pesticides and clarified the enforcement mechanism for failure to comply. Section 3(a) of FIFRA, 7 U.S.C. 136a(a), provides that ``[to] the extent necessary to prevent unreasonable adverse effects on the environment, [EPA] may by regulation limit the distribution, sale, or use ... of any pesticide that is not registered ... and is not the subject of an experimental use permit under section 5 or an emergency exemption under section 18.'' Violations of such regulations are enforceable under sections 12(a)(2)(S) and 13 of FIFRA. In addition to section 5, these regulations are being proposed pursuant to sections 3(a) and 25 of FIFRA. II. Historical Development In 1984, EPA issued an interim policy statement entitled ``Microbial Pesticides: Interim Policy on Small-Scale Field Testing'' (49 FR 40659, October 17, 1984). This statement announced that the presumption in the 1975 EUP regulations (40 CFR 172.3) would not automatically apply to tests using genetically altered and nonindigenous microbial pesticide products and that the Agency should be notified before initiation of any such testing. Since 1984, the Agency has used this notification scheme to evaluate small-scale tests involving genetically altered and/or nonindigenous microbial pesticides for possible risk to human health or the environment and to determine whether EUPs would be required before the tests could be initiated. Subsequent to publication of the Interim Policy, this same basic position was published for comment in EPA's section of the Office of Science and Technology Policy (OSTP) ``Proposal for a Coordinated Framework for Regulation of Biotechnology'' (49 FR 50856, December 31, 1984). The final OSTP statement of policy was published on June 26, 1986 (51 FR 23302, June 26, 1986). In the 1986 Policy Statement, the Agency stated its intention to codify the major elements of the notification procedure in the EUP regulations (40 CFR part 172). The development of this proposed rule began at that time. In June 1988, as required by FIFRA section 25, the Agency made available copies of a draft proposal to the U.S. Congress and the U.S. Department of Agriculture (USDA). A subpanel of the FIFRA Scientific Advisory Panel (SAP) reviewed, in a public meeting held November 22, 1988, a draft similar to that reviewed by USDA and Congress, but modified to reflect USDA's comments. On February 15, 1989 (54 FR 7026, February 15, 1989), the Agency issued a Federal Register notice requesting comments on three issues, and announcing availability of a draft proposal (dated January 12, 1989) in the public docket to facilitate comment. Both of the draft rule proposals included for review and comment, a scope definition essentially equivalent to the scope identified as Option 1 in this proposal. Public comments on the 1984 Interim Policy, the 1984 ``Proposal for a Coordinated Framework for Regulation of Biotechnology,'' the 1986 statement of policy in the ``Coordinated Framework for Regulation of Biotechnology,'' the EPA's January 1989 draft proposal, and in response to the February 15, 1989 Federal Register notice are available in the public docket. These comments have been taken into consideration in development of this proposal. The docket also contains the comments provided by the USDA and the FIFRA SAP subpanel in 1988, together with the Agency's responses. In 1989, the Ecological Society of America (ESA) and the National Academy of Sciences (NAS) published reports on the assessment of potential impacts related to the use of genetically modified organisms in the environment. Respectively, these reports are titled ``The Planned Introduction of Genetically Engineered Organisms: Ecological Considerations and Recommendations'' (Tiedje, J. M. et al., 1989, Ecology 70:297 - 315) and ``Field Testing Genetically Modified Organisms: Framework for Decisions,'' (National Academy Press, 1989, Washington, DC). The Agency has considered both reports in the development of this proposed rule. Also in October 1989, a subcommittee of the Federal government's interagency Biotechnology Science Coordinating Committee (BSCC) was charged with drafting principles for the scope of organisms subject to Federal oversight of planned introductions into the environment. The subcommittee developed a preliminary definition that was made available, along with three other approaches it had examined, for public meetings of the EPA's Biotechnology Science Advisory Committee (BSAC) and USDA's Agricultural Biotechnology Research Advisory Committee (ABRAC). Both committees commented on the preliminary definition. Subsequently, the OSTP, in coordination with the Biotechnology Working Group of the President's Council on Competitiveness, developed a proposed policy, based on the preliminary definition reviewed by the BSAC and ABRAC, entitled ``Principles of Scope of Oversight for the Planned Introduction into the Environment of Organisms with Modified Hereditary Traits'' which was published for public comment in the Federal Register of July 31, 1990 (55 FR 31118). In September 1990, the Agency made available copies of a draft proposed rule (dated September 4, 1990) which included a scope definition that used language adapted from the July 1990 proposed policy on scope of oversight. That definition was similar to Option 2 in this proposal. The September 1990 draft also included for comment the initial scope definition, set forth as Option 1 in this proposal, that was directly tailored to FIFRA and pesticides. At a public meeting held September 7, 1990, a subcommittee of the BSAC reviewed these two scope definitions. The subcommittee developed a third scope definition that attempted to merge the two options contained in the September 4, 1990 draft and provided recommendations in a final report dated November 14, 1990. The final report is available in the public docket and is summarized in Unit VII.A. of this preamble. On September 26, 1990, a subpanel of the FIFRA SAP reviewed the September 4, 1990 draft proposal containing scope definitions essentially equivalent to Options 1 and 2 in this proposal, as well as the draft third definition developed by the BSAC subcommittee at its September 7, 1990 meeting. The recommendations of the FIFRA SAP subpanel are summarized together with the Agency's responses in Unit VII.B. of this preamble. The full report of the subpanel (dated October 9, 1990) is available in the public docket. Subsequently, additional guidance by the United States Government concerning Federal oversight of biotechnology products was provided in the four principles of regulatory review recommended in the ``Report on National Biotechnology Policy,'' issued in February 1991 by the President's Council on Competitiveness. The first principle indicates that agencies should focus on the characteristics and risks of the biotechnology product, and not on the process by which it is created. The second principle states that for biotechnology products that require review, regulatory review should be designed to minimize regulatory burden while assuring protection of public health and welfare. This includes developing expedited review procedures for products likely to pose lesser risk, and clarifying the jurisdictions of the regulatory agencies to avoid unnecessary confusion and delay. The third principle states that regulatory programs should be designed to accommodate the rapid advances in biotechnology, and performance-based standards are generally preferable to design-based standards. The fourth principle indicates that all regulation in environmental and health areas should use performance-based standards for compliance. On February 27, 1992 (57 FR 6753), the OSTP published a policy announcement entitled ``Exercise of Federal Oversight Within Scope of Statutory Authority: Planned Introductions of Biotechnology Products Into the Environment,'' which finalized the proposed policy that was published July 31, 1990. This notice set forth the basis for Federal agencies' exercise of oversight within the scope of discretion afforded by their statutes. It indicated that oversight should be exercised only where the risk posed by the introduction is unreasonable, that is, when the value of the reduction in risk obtained by oversight is greater than the cost thereby imposed. The Agency notes that the final OSTP policy statement rejected an approach that relied upon exclusion categories that were substantially similar to the five exclusion categories provided for in Option 2. As discussed in that document, the proposed OSTP exclusion categories were rejected for several reasons, in part because an appropriate risk basis for these exclusions had not been provided. The Agency believes that exclusion categories can be used effectively to reduce the burden of regulations, but that such categories should only be used when they are supported by appropriate risk-based rationales. Because Option 2 is substantially similar to the approach in the proposed policy on oversight, the Agency is no longer considering Option 2. EPA has retained Option 2 in the preamble only for illustrative and comparative purposes and will not consider Option 2 during development of the final rule. As indicated above, EPA currently prefers Option 1, but is also interested in comments on Option 3. The principles espoused in the 1991 National Biotechnology Policy and the February 27, 1992 announcement are to encourage the use of innovative new biotechnology products, and EPA has used these concepts in developing this proposal. The rule now being proposed reflects changes in the September 1990 draft made in response to public comments, the recommendations of the 1990 FIFRA SAP subpanel and 1990 BSAC subcommittee, and the 1990, 1991 and 1992 Federal biotechnology policy statements. In addition to scope Options 1 and 2, which have been reviewed and commented on one or more times by the FIFRA SAP subpanel and the BSAC subcommittee, this proposal also contains a third option, Option 3, which was developed recently during interagency discussions. Option 3 has not been reviewed by EPA's SAP or BSAC, nor has it been a part of the public comment process prior to this proposal. III. Proposed Regulatory Changes A. Rationale for Notification Pesticides by their very nature are designed to disrupt or alter the environment in which they are used. To achieve their intended beneficial purpose, they must have an adverse or otherwise limiting effect on some organism. Microbial pesticides achieve their effect in a number of ways. They may, for example, produce a substance that exerts a toxic effect; they may be pathogens that cause disease in the organisms they infect; or by simply being present, they may outcompete and displace certain types of pests. As with other types of pesticides, a microbial pesticide may also affect nontarget organisms. EPA, to date, has registered 24 different microbial pesticides in hundreds of different formulations. These microbial pesticides have, in general, enjoyed a history of safe use. They appear to be kept in check by various factors such as the actions of other organisms and the parameters of the physical environment that exist in the environment where the microbial pesticide is used. For example, microorganisms that are present in the environment of use may interact with the microbial pesticide in a number of ways. Indigenous microorganisms may compete with the microbial pesticide for space and nutrients; they may modify the environment to repel other microorganisms such as the microbial pesticide; or they may prey on the microorganisms comprising the microbial pesticide. Environmental conditions, such as temperature, humidity, pH, and available nutrients also limit the applied pesticide's survival and growth. These factors together are referred to in this preamble as ``natural control mechanisms.'' The characteristics of the microbial pesticide play a role in the effectiveness of natural control mechanisms. If the microorganism is too weak to compete effectively against other microorganisms, or to withstand environmental conditions, it will be easily held in check by natural control mechanisms. Experience suggests natural control mechanisms exist in most environments where the microbial pesticides developed to date have been applied. Because of the likelihood that natural control mechanisms will limit microbial pesticides, the Agency has generally presumed that the relatively small amounts of microbial pesticides used in small-scale testing would not pose unreasonable adverse effects, i.e., the benefits of these types of tests would outweigh the risks. However, as first indicated in the 1984 Interim Policy Statement, it is now possible to develop microbial pesticides expressing new pesticidal properties. Such properties may allow for significantly new or expanded host ranges, new or enhanced toxin production, and new fitness and survivability characteristics. In addition, the genetic components responsible for the added or altered pesticidal properties may be mobile and may allow for transfer of the pesticidal traits to other organisms that would otherwise be unable or unlikely to acquire these pesticidal properties. Many of these kinds of microbial pesticides would have been unlikely to arise under natural conditions, and may not be subject to existing natural control mechanisms. Because these microbial pesticides may raise different risk concerns than the more traditional microbial pesticides in small-scale testing, the Agency believes that the presumption that they would not pose unreasonable adverse effects should not automatically apply. In 1984, the Agency set forth a notification requirement that had a broad scope of coverage: specifically, all genetically altered and nonindigenous microbial pesticides would be subject to screening before application in the environment. Since then, the Agency has had almost 8 years experience reviewing over 75 notifications for small-scale testing with genetically altered and nonindigenous microbial pesticides. Based on that experience, and a growing body of information from other sources such as the scientific literature, EPA has concluded that certain of these microbial pesticides need not be subject to the limited screening involved in the EPA notification process. Accordingly, one goal in developing the scope of coverage for this proposed rule is to reduce regulatory burden by eliminating the notification requirement for those microbial pesticides that scientific knowledge, experience, or expertise indicate do not warrant review because they are unlikely to pose unreasonable adverse effects at this stage of development. In other words, the scope of coverage for this rule should be reduced, from that articulated in 1986, to focus only on those microbial pesticides for which the Agency has risk concerns or where the Agency lacks sufficient information or knowledge to conclude that their use at small-scale is unlikely to cause unreasonable adverse effects. Another EPA goal is to implement a scope that clearly identifies those microbial pesticides subject to the notification requirement in a way that could be easily understood and used. Such a scope would make sufficiently clear to the regulated community, the Agency and other interested parties, whether a specific microbial pesticide is subject to the notification requirement. B. Description of Notification A notification would contain sufficient data and information to allow EPA to review the proposed test, including the identity of the microbial pesticide, a characterization of its relevant biology and ecology, a description, if applicable, of how the microbial pesticide has been modified, and a description of the objectives, experimental design, and other relevant parameters of the proposed test. Proposed subpart C at 172.48 includes a discussion of the kinds of data and information to be submitted in a notification. The notification could be in the form of a letter. It may describe a range of testing, from a single specific test to a complete research program. A notification for a research program could address, for example, multiple year testing in multiple sites with multiple microbial pesticides. This approach has been employed with some of the notifications submitted under the 1984 and 1986 policy statements, and EPA finds it advantageous to both the Agency and submitters to treat a series of field tests that are variations on a theme under a single notification. Data and information provided to the Agency in a notification may be claimed as confidential business information (CBI), and should be accompanied by comments substantiating the CBI claims. (See 172.46(d)). Agency review of a notification would be completed within 90 days. At the conclusion of the review, the Agency may make one of the following determinations: approve the test; approve the test without requiring an EUP as long as certain modifications in the proposed test plan are incorporated; require additional information; require an EUP for the test; or disapprove the test because of the potential for unreasonable adverse effects. In the past, EPA has, in several instances, informed submitters on an individual basis when no further notification to EPA was required for certain specific microbial pesticides, even though these microbial pesticides were within the scope of the 1984 and 1986 policies. The Agency has taken this action in those instances where sufficient information was available to EPA to approve a range of future small-scale testing without specific prior notification for each test. EPA anticipates it will continue this approach, where warranted, under the current policy and when a final rule is in place. C. Proposed Regulatory Scheme The Agency proposes to revise 40 CFR 172.3 to clarify its rationale for presuming that an EUP is not required prior to small-scale testing with most pesticides. The Agency would modify the language of the rule to clarify that the determination of whether an EUP is required is based on risk considerations, rather than on a definitional presumption about whether the substance is a pesticide. Whether a substance is a pesticide, and therefore under the jurisdiction of FIFRA, is governed by the definition in section 2(u) of FIFRA; whether a pesticide should be regulated under FIFRA is governed by risk/benefit considerations and the availability of appropriate regulatory alternatives. EPA believes that EUPs are usually not warranted for small-scale testing because most applications of most pesticides are presumed not to involve unreasonable adverse effects to human health or the environment. The Agency also proposes, by adding a subpart C to the existing EUP regulation (40 CFR part 172), to incorporate the requirement that the Agency be notified before initiation of small-scale testing with microbial pesticides whose pesticidal properties have been enhanced or imparted by the introduction of genetic material that has been deliberately modified. This is referred to in this preamble as Option 1. Two other scope definitions, designated Options 2 and 3, are also discussed in this preamble. Currently, the Agency requires notification for small-scale testing of all genetically altered and nonindigenous microbial pesticides. EPA now, in the proposed regulatory text, proposes to limit the focus of the notification requirement to a smaller group of microbial pesticides. The proposed notification scheme would codify the Agency procedure of screening planned small-scale tests to evaluate the potential for adverse effects on human health or the environment and allow the Agency to take further action, if appropriate. Testing conducted in a facility with adequate containment and inactivation controls would not be subject to the notification requirement. Responsibility for selection and use of adequate containment and inactivation controls would lie with the researcher or institution conducting the test (See Unit V.A. of this preamble). A mechanism for designating, in the future, exemptions from the requirement for notification prior to testing at the small-scale stage, as information and/or experience indicates this is warranted, is included at proposed 172.52. Using this mechanism, certain subgroups of the microbial pesticides, otherwise subject to notification, could, on the basis of scientific knowledge and experience, be added to a list of exemptions from the notification requirement. Proposed 172.57 and 172.59 are included to enable the Agency to address situations where small-scale tests covered by subpart C result in unanticipated and untoward effects. Proposed 172.57 addresses situations where a person using a microbial pesticide in small-scale testing obtains information concerning the potential for unreasonable adverse effects, but there is no threat of immediate or serious harm to human health or the environment. This section would require that person to submit such information to EPA within 30 days so that the Agency can evaluate the information and take any necessary action to minimize the potential for adverse effects. In situations where threat of harm to human health or the environment is immediate and serious, proposed 172.59(a) sets out the manner in which EPA would act immediately to prevent adverse impacts. For example, if necessary and appropriate to the specific situation, EPA may use its authority under FIFRA section 16(c) to prevent continuance of the experiment. Such actions would be taken only when there is a tangible threat of serious harm that must be attended to without delay. EPA does not intend to use the authority in proposed 172.59(a) to respond to situations that could be addressed in other, less precipitous ways. The provisions set forth in proposed Subpart C (172.43 through 172.59) for the review of small-scale tests of certain microbial pesticides would not affect the already established Agency procedures for the review of pesticides for EUPs or for registration purposes. Together, the notification procedure and the existing EUP procedures would provide oversight of microbial pesticides that meets EPA's objectives under FIFRA, as well as those set forth in the 1986 ``Coordinated Framework for Regulation of Biotechnology,'' the 1990 ``Proposed Principles on Scope of Oversight,'' the 1991 ``Report on National Biotechnology Policy,'' and the 1992 ``Exercise of Federal Oversight Within Scope of Statutory Authority.'' EPA believes that this notification procedure is also consistent with the recommendations contained in the ESA and NAS reports, and the recommendations of the FIFRA SAP and BSAC concerning the assessment and screening of microbial pesticides. IV. Options for Scope of Coverage A. Identification of the Options To provide a full opportunity for analysis and comment by the public, this preamble discusses three options for redefining the scope of microbial pesticides subject to screening before small-scale testing in the environment. The Agency's goal in setting forth these options is to discuss alternative approaches to identifying those microbial pesticides having the greatest potential to pose risks, or those where sufficient information and knowledge are lacking about the potential risk when the microbial pesticide is introduced into the environment. Each option is accompanied by definitions and/or footnotes that have been developed to provide the necessary specificity for use within the regulatory context of FIFRA. The three options are presented below, followed by the Agency's analysis of the options in Unit IV.B. of this preamble, and a discussion of the implementation of these options within the FIFRA regulatory context in Unit IV.B.4. of this preamble. For a variety of reasons discussed in the analysis and in the summary in Unit VI. of this preamble, the Agency prefers Option 1, and it is embodied in the proposed regulatory text. EPA is also interested in comments on Option 3. As noted above, Option 2 is discussed for illustrative and historical reasons. Option 1: Microbial pesticides whose pesticidal properties have been imparted or enhanced by the introduction of genetic material that has been deliberately modified. Key terms used in Option 1 are defined as follows: 1. ``Pesticidal property'' means a characteristic exhibited by a microorganism that contributes to the intentional use of the microorganism to prevent, destroy, repel, or mitigate a pest or to act as a plant regulator, defoliant, or desiccant. 2. ``Introduction of genetic material'' means the movement of nucleotide sequence(s) into a microorganism, regardless of the technique used. 3. ``Deliberately modified'' means the directed addition, rearrangement, or removal of a nucleotide sequence(s) to or from genetic material. Option 2: Microbial pesticides that have been deliberately modified in hereditary traits, with the exception of: 1. Microorganisms modified solely: a. Through chemical or physical mutagenesis. b. By the movement of nucleic acids using physiological processes including, but not limited to, transduction, transformation, or conjugation;Also excluded are microorganisms modified solely by anastomosis.or c. By plasmid loss or spontaneous deletion. 2. Organisms that have been modified by the introduction of noncoding, nonexpressed nucleotide sequences that cause no phenotypic or physiological changes in the parental organism.Also excluded are microorganisms modified as in 1 or 3 above that have also been modified by the introduction of noncoding, nonexpressed nucleotide sequences that cause no phenotypic or physiological changes. 3. Organisms resulting from a deletion, rearrangement, or amplification,Applies only to microorganisms where the amplification has not imparted, enhanced, or altered pesticidal properties.within a single genome, including its extrachromosomal elements.Also excluded are microorganisms resulting solely from a point mutation. This definition uses several key terms and phrases that require further clarification as follows: a. ``Deliberately modified in hereditary traits'' means modified by alteration of the genome. b. ``Genome'' means the sum total of chromosomal and extrachromosomal genetic material of an isolate and any descendants derived under axenic culture conditions from that isolate. c. ``Organisms'' means microorganisms. d. ``Movement of nucleic acids'' means movement of nucleotide sequences into a microorganism. e. ``Physiological processes'' means there has been no directed addition, rearrangement, or removal of a nucleotide sequence(s) to or from the nucleic acids that are moved. In addition, the recipient microorganism must not have lost the ability to recognize and cleave foreign genetic material and must not have been exposed to conditions to induce competence artificially by treatments that render the microorganism surface structure permeable to transforming genetic material. f. ``Organisms resulting from rearrangements'' means microorganisms resulting from translocations or inversions. g. ``Noncoding, nonexpressed nucleotide sequences'' means the nucleotide sequences are not transcribed and are not involved in gene expression or replication. Examples of noncoding, nonexpressed nucleotide sequences that cause no phenotypic or physiological changes in the recipient include linkers, adaptors, homopolymers, and flanking sequences. Option 3: Indigenous microbial pesticides for which specific pesticidal activities have been created or increased by deliberate processes or techniques. Notification is not required for microbial pesticides whose pesticidal activities have been increased, but which are unlikely to pose a greater risk in the test site environment, in terms of increased host range, competitiveness, survivability, or genetic mobility, compared to the microorganism(s) from which they were derived. Notification is not required for microorganisms whose phenotype has been changed only by the microorganism's introduction into a new environment, but which are unlikely to pose a greater risk in the test site environment resulting from an increase in host range, competitiveness, survivability, or genetic mobility. Key terms used in Option 3 are defined as follows: 1. ``Pesticidal activities,'' for the purpose of this option, means hazard characteristics expressed by the microorganism, which is the active ingredient, that prevent, repel, destroy or mitigate a pest or act as a plant growth regulator, defoliant, or desiccant through toxin production, infectivity, pathogenicity, or virulence. Pesticidal activities do not include noncytotoxic modes of action such as those brought about by niche exclusion, substrate competition, or nutrient sequestration. 2. ``Created'' means the microorganism has been given a pesticidal activity that is not part of the normal genetic complement of the species in nature. 3. ``Increased pesticidal activity'' means an augmentation of a pesticidal activity that can be shown to be part of the normal genetic complement of the species in nature. 4. ``Deliberate processes or techniques'' means the intentional movement of the microorganism to a new environment or a change in the genetic information of the microorganism resulting from natural breeding, selection for spontaneous mutations, chemical or physical mutagenesis, transduction, transformation, conjugation, cell fusion, recombinant DNA or other genetic manipulations. 5. ``Test site environment'' means the immediate test site and the area surrounding the test site to which the microorganism or its genetic material may reasonably be expected to be dispersed. 6. ``Genetic mobility'' means the horizontal movement [i.e., from the genome of one species to the genome of another] of genetic material. Option 1 uses an ``inclusionary'' scope. This approach is termed ``inclusionary'' because it is based on an initial statement that describes which microbial pesticides are included in the scope and therefore subject to notification. Options 2 and 3 are termed ``exclusionary'' because they both begin by circumscribing a larger group of microbial pesticides and then delineate subsets to be excluded from the scope. B. Analysis of Options 1. Options 1 and 2. Options 1 and 2 are discussed together because they share many of the same key terms and definitions. Options 1 and 2 are approaches in which the EPA has made the initial assessment of the potential risk presented by certain categories of small-scale testing with microbial pesticides. In these options, EPA directly indicates in the scope definitions the categories of microbial pesticides subject to notification. Options 1 and 2 are based on three major premises: (1) Notification should be limited to tests involving microbial pesticides with the potential for presenting new and different hazard traits and/or a potential that organisms which heretofore might not have been exposed to these traits could be exposed, particularly when this exposure occurs through new or additional routes; (2) that a site-specific analysis of risk potential for tests other than those in (1) above is not necessary, and these tests can be excluded from the notification requirement; and (3) the decision of which tests are subject to notification is made by EPA, and encoded in the scope definition. EPA's decision is based on its 40 years of experience in regulating microbial pesticides, including 8 years of experience evaluating genetically altered and nonindigenous microbial pesticides at all stages of product development and registration, as well as the knowledge and expertise of its personnel and other scientists in fields such as microbial ecology, plant and insect pathology, soil microbiology and molecular biology. Options 1 and 2 create a structure (See Unit IV.B.3. of this preamble) wherein the assessment of whether a test is subject to notification to EPA is made on the basis of simple and directly addressable criteria that form the scope definitions. Under these approaches, all interested parties (e.g., industry, researchers, public interest groups, EPA) would, in most instances, deduce from a reading of the definitions alone whether a test involving a specific microbial pesticide is subject to the notification requirement. Both options significantly reduce the number of notifications that would be sent to EPA relative to existing EPA policy. Option 1 focuses the scope of microbial pesticides subject to notification through a single statement that directly describes the types of tests that would be subject to notification. Option 2 defines the scope of microbial pesticides subject to notification through a somewhat broader initial statement, which is then narrowed by exclusions. Option 1 identifies and focuses attention on microbial pesticides with (1) new or different hazard trait(s); and (2) the potential to present new or different exposures, e.g., organisms which heretofore might not have been exposed to a particular substance might now be exposed to that substance through the microbial pesticide. EPA judges pesticides in these categories to present relatively greater potential for risk than those microbial pesticides EPA would no longer subject to the notification requirement. The following discussion provides the rationale for EPA's determination of those microbial pesticides which would be subject to the notification requirement and those that would not under Options 1 and 2. Examples are provided in order to illustrate the types of issues presented by microbial pesticides covered by Options 1 and 2. Useful and effective microbial pesticides can now be developed by introducing new pesticidal properties into a microorganism. This can be accomplished, for example, by giving a microorganism the ability to produce a toxin that heretofore, it could not produce. A gene encoding a toxin could be isolated, for example, from a parasitic wasp, introduced into a microorganism, and be functionally expressed by the microorganism (Example 1). Such a microbial pesticide might present new hazard and exposure considerations. The microorganism, which had no previous pesticidal properties, is now able to produce a potent toxin, which might present a new hazard consideration. The microorganism's acquisition of the ability to produce the toxin also creates a potential for either increased exposures of nontargets, or exposure of a different range of nontarget organisms. For example, when the toxin is produced by the parasitic wasp, generally only those insects preyed upon by the wasp are exposed to and affected by the toxin. However, when the toxin is produced by the microorganism, a new range of organisms may be exposed to the toxin. If the microorganism colonizes leaves or roots, then any insects or other organisms feeding on, or living in close association with, a plant colonized by the microorganism could be exposed to the toxin and could be adversely affected by such exposure. A newly acquired toxin production capability may also impart selective advantage and/or competitive characteristics such that the microbial pesticide could establish itself in the environment and continuously present these new exposures. It is possible that the newly acquired trait could assist in overcoming natural control mechanisms. For example, organisms killed by the toxin may serve as an additional source of nutrients for the microorganism. This may allow the pesticidal microorganism to exhibit superior multiplication and dissemination compared to other microorganisms whose populations are kept in check because they do not have access to additional nutrients. There is also the possibility that the genetic material encoding the pesticidal trait could move, under natural environmental conditions, from the microorganism that was the original recipient, into other microorganisms that would have otherwise been unlikely to acquire it. These other microorganisms may occupy different environmental niches than the original recipient. Such unintended movement may allow for ever increasing environmental exposure as the gene is transferred from one type of microorganism to another. A wider variety and greater number of nontarget organisms could thereby be exposed to the toxin. The ability of a microorganism to function as a microbial pesticide can also be increased by enhancing the pesticidal properties that the microorganism already possesses. For example, the efficacy of Bacillus thuringiensis could be enhanced by modifying its delta endotoxin gene so it encodes a more potent toxin. It may also be possible to broaden the target spectrum of the microbial pesticide through modification of the gene encoding the toxin. For example, in the case of B. thuringiensis, the microorganism produces a protein molecule which itself does not have insecticidal activity; i.e., the microorganism produces a protoxin. In order for toxic activity to occur, the protoxin must be broken down into fragments or subunits, one of which is toxic. It is believed that most insects are unaffected by B. thuringiensis because their gastrointestinal tract does not degrade the protoxin to produce the toxic subunit. If the gene producing the protoxin were modified so that the B. thuringiensis produced only the insecticidally active subunit, and the active subunit were coupled with another protein to enhance transport across membranes, additional insect species could be susceptible to this microbial pesticide (Example 2). Such microbial pesticides may be able to compete in the environment and could thus become a permanent part of the B. thuringiensis population. A microorganism's pesticidal activity could also be enhanced by changes to genes other than those that encode the toxin, but which nonetheless, affect pesticidal properties. For example, changes could be made in genes controlling host specificity. When this is done, the range of hosts the microorganism can affect could be decreased, or increased to encompass other types of organisms that were not previously affected by the microbial pesticide (Example 3). Some modifications can be undertaken to increase the ability of the microorganism to survive. For example, modifications enhancing resistance to UV radiation could increase microorganisms' ability to survive solar radiation (Example 4). Such an ability would be important for microorganisms living on plant leaves, and could lead to microbial pesticides with increased pesticidal properties. For example, if a toxin producing microorganism persisted longer in the environment because of an ability to resist solar radiation, additional nontarget organisms might be adversely affected because these nontargets have greater opportunity to chance upon the toxin, and/or might be exposed to the toxin for a sufficiently long period of time for the adverse effects to occur. The above are examples of the kinds of microbial pesticides that are the general focus of Options 1 and 2. They are directly the focus of Option 1 since it identifies microbial pesticides whose pesticidal properties have been imparted or enhanced with the term ``enhanced'' interpreted broadly. For example, ``enhanced'' would include circumstances involving an increase in the ability of a microbial pesticide to survive. It would also include any increase, improvement, extension, augmentation, intensification, or amplification of a pesticidal property, and would include situations where the mobility of the pesticidal property is increased. Option 2 indirectly focuses on these microbial pesticides through a broader initial scope and exclusions for categories of microbial pesticides which do not have these properties. Because of the potential for microbial pesticides covered by Options 1 and 2 to express new or enhanced pesticidal traits, and to disseminate and increase in numbers and biomass, the Agency believes that the risk issues associated with such microbial pesticides should be considered by EPA at the small-scale testing stage, rather than deferring EPA consideration to later stages of testing and development. Both Options 1 and 2 exclude from notification all microbial pesticides comprised of microorganisms simply isolated from the environment (naturally occurring), and laboratory generated microbial pesticides similar to those that would be likely to occur in microbial populations in nature. As mentioned previously, EPA has a significant amount of experience with naturally occurring microbial pesticides. EPA's experience to date suggests that the populations of most microbial pesticides of this type are limited, often by natural control mechanisms, so that they generally die off or return to low numbers. Thus, these microbial pesticides are not likely to present new hazard or exposure issues when tested at small-scale, and do not necessitate a site-specific analysis of potential risk. (The exception to this statement may be certain nonindigenous microorganisms. See Unit IV.B.5. of this preamble for a discussion of EPA's position on such microorganisms.) EPA believes that certain laboratory-generated microbial pesticides will behave like the population from which that microbial pesticide was derived. No population of microorganisms in the environment is homogenous in genetic composition, or in traits expressed. Members of a population change their characteristics through, for example, random loss of genetic material (i.e., random deletions, including plasmid and chromosome loss) and rearrangement of genetic material within a microorganism. Random loss and rearrangement of genetic material can result from exposure to UV radiation, starvation, and exposure to mutagenic chemicals, as well as from errors when the microorganism duplicates its genetic material. These types of conditions and events occur in nature, and some members of a population will, at any time, experience loss or rearrangement of genetic material. Therefore, microorganisms that have experienced these types of changes in the laboratory, are likely to exhibit characteristics within the range of characteristics exhibited by populations in the environment. A microbial pesticide that results from the transfer of genetic information, under conditions simulating conditions in nature, would also be likely to be similar to members of the population in nature. Bacteria, for example, engage in such transfer through: (1) transduction, a process in which a virus can pick up the genetic information encoding for a heritable trait(s) of one bacterium and transfer it to the bacterium that it subsequently infects; (2) transformation, a process in which a bacterium takes up genetic material from the environment (perhaps released into the environment by the death of another microorganism); and (3) conjugation, a process in which genetic material is transferred from one bacterium to another through direct physical contact. Successful transfer of genetic information depends, among other things, on the ability of the recipient microorganism to incorporate and express the genetic information. Transfer of genetic information is restricted generally to members of a single population, since the cellular machinery that expresses genetic information generally is highly organism specific. Occasionally, members of more distantly related populations of microorganisms may exchange genetic information, e.g., in conjugation, but these wider exchanges have limitations. In any event, these types of transfers of, and changes, in genetic information are likely to occur in nature. Therefore, some members of each population probably already possess genetic information that can be transferred into the population by natural transduction, transformation, and conjugation. Thus, microorganisms produced in the laboratory under conditions simulating conditions in nature are likely to be the same as, or similar to, variants found in natural microbial populations. Thus, they, would not present new hazard or exposure issues and would be subject to the constraints imposed by the environment. Although Options 1 and 2 are similar with respect to the kinds of microbial pesticides covered and not covered, the two options differ in two important respects. First, while Option 2 includes most modifications that enhance, impart, or alter pesticidal properties by the introduction of modified genetic material, it is not limited to this group of modifications. For example, Option 2 would also cover microbial pesticides modified by the introduction of marker genes that have been inserted only to improve the ability to identify and detect the microbial pesticide. Option 2, which is not as specifically targeted to pesticides as Option 1, includes these kinds of microbial pesticides since the exclusion categories on which it is based are not so precisely drawn as to exclude only marker genes. Therefore, Option 2 casts a somewhat broader net in order to capture for review, the few microbial pesticides that may fall in the same category as marker genes and that may pose risk concerns. A second area where the options differ is that Option 1 would encompass within the scope, microbial pesticides in which pesticidal properties have been altered by the deletion or rearrangement of genetic material within the genome of the microorganism when the deletion or rearrangement has been brought about by isolating a segment of genetic material from a microorganism, deliberately modifying it, and subsequently returning that segment to the microorganism. Option 2 does not capture this category of microorganism within its scope. The argument supporting the approach in Option 2 is that these kinds of deletions and rearrangements can only: (1) inhibit the expression of characteristics possessed by the parent organism or, (2) allow previously unexpressed characteristics to manifest themselves. Since no new genetic material is added, no characteristic can be expressed that could not potentially have been expressed by the parental microorganism, or that may not already be expressed by a variant in the natural population. The microorganism is not likely to possess characteristics outside the range of those that could occur in the environment. It would, thus, be subject to natural constraints. However, for microbial pesticides, the intent underlying such modifications would usually be to cause the microorganism to exhibit specific pesticidal characteristics, such as enhanced toxin production, increased virulence or expanded host range. It is well documented that changes in these kinds of characteristics can result from deletion and rearrangement of genetic material. Deletions and rearrangements brought about by deliberately modifying a segment of genetic material from a microorganism and returning that segment to the microorganism (i.e., targeted changes) may present somewhat different considerations than microbial pesticides that have acquired such characteristics randomly as a result of insults such as UV radiation, exposure to toxic chemicals or starvation conditions. Targeted modifications minimize the possibility of unintended changes occurring in other parts of the microorganism's genetic information that could render it less fit for survival, or that could trigger rounds of repair activity leading to changes in the desired modification. Moreover, targeted changes can be engineered to be more stable, and, on average, less likely to revert to the characteristic that existed prior to the change. Targeted changes in pesticidal properties may result in microbial pesticides with a relatively higher potential for maintaining and expressing the changed characteristic(s) than those microorganisms resulting from random changes. Thus, targeted deletions and rearrangements in microbial pesticides may present relatively higher levels of potential risk than random changes. As a result, EPA has, consistent with the advice of the FIFRA SAP subpanel (see Unit VII.B. of this preamble), elected in Option 1 to propose that some microbial pesticides resulting from a targeted deletion or rearrangement would be subject to the notification requirement. However, EPA proposes in this rulemaking a mechanism that could be used to exempt categories of microbial pesticides (See Unit V.B. of this preamble). Should experience and/or public comment indicate it is warranted, EPA could exempt from notification those microbial pesticides that result from a targeted deletion or rearrangement. EPA requests comment at Unit VIII.G. on this issue. 2. Option 3. Option 3 is an approach in which the researcher (or research institution) makes the initial assessment of the potential for risk presented by the test. Option 3 is based on three major premises: (1) Notification should be limited to microbial pesticides that have the potential to pose greater risk because of increased hazard and/or exposure compared to their parental(s); (2) the researcher (or the research institution) is in the best position to make the initial determination of whether notification is required for a test; and (3) the researcher can choose to evaluate the potential risks of the specific small-scale experiment (including the test site environment) and determine if it satisfies premise (1) above. Option 3 defines the scope of microbial pesticides potentially subject to notification through a broad initial statement that brings in many tests; it then proceeds to narrow the scope focus in two ways. First, certain key terms and definitions narrow the scope. Second, Option 3 narrows the scope through two exclusions based on exposure considerations. These terms and definitions were developed to give researchers addressable criteria from which to determine the need to notify EPA of a planned test. The breadth of the initial statement of scope is determined by the words ``by deliberate processes or techniques.'' For this option, ``by deliberate processes or techniques'' refers to changes in the genetic information possessed by the microorganism and/or the intentional movement of the microorganism to a new environment. A change in the genetic information of the microorganism can be effected in a number of ways, and all of these are within the initial statement of scope. These include natural breeding, selection for spontaneous mutations, chemical or physical mutagenesis, transduction, transformation, conjugation, and recombinant DNA, or other genetic changes such as those arising from anastomosis, plasmid loss, site-directed mutagenesis, and cell fusion. Selection for spontaneous mutation would include the deliberate use of selective pressure to affect the efficacy of the microbial pesticide. For example, viruses whose virulence has been enhanced by serial passage would be within the initial statement of scope. In serial passage, a host is successively inoculated with the virus; the progeny viruses are then screened and those progeny with the most pesticidal activity are selected. This process is repeated sequentially, if needed, to increase the virus' virulence. The term ``natural breeding'' would include microorganisms that have been cultured. The initial statement of scope also includes microbial pesticides moved from one environment of testing to another, different or ``new environment,'' whether they have experienced changes in genetic information or not. The ``new environment'' could be a significant change in geographic location, climatic condition, ecosystem or habitat. The broad initial statement of scope is then narrowed by several other key terms and definitions. First, the definition of ``pesticidal activities'' narrows the scope to address only those microbial pesticides which exert their pesticidal effects through the specific modes of action of toxicity and/or host-pathogen interactions. Microbial pesticides that act through other mechanisms are outside of the scope and would not be subject to the notification requirement. ``Pesticidal activities'' do not include noncytotoxic modes of action such as those brought about by niche exclusion, substrate competition, or nutrient sequestration. The terms ``created'' and ``increased'' further limit the scope. In Option 3, ``created'' means that the microbial pesticide has acquired the ability to perform as a pesticide via toxin production and/or host-pathogen interaction, as a result of the deliberate introduction of genetic material that is not part of the normal genetic complement of the species in nature. ``Increased'' means that the ability of the microorganism to act as a pesticide through toxin production and/or host-pathogen interaction has been augmented, and that the genetic material controlling these activities is part of the normal genetic complement found in the species in nature. Microorganisms whose genetic information has not been changed but whose pesticidal activity is increased by movement to a new environment would fall in this category. Microorganisms whose pesticidal activities have not been changed or have been decreased, through changes in genetic information or movement from one environment to another, would not be within the scope. For example, attempts are being made to reduce the host range of the plant pathogen, Sclerotinia sclerotiorum, and should this pathogen be field tested as a microbial pesticide, it would not trigger notification under Option 3 because its pesticidal activities have been decreased. Having narrowed the scope through these key terms and definitions, Option 3 then utilizes two exclusions to remove certain other microbial pesticides from the notification requirement. These exclusions are based on an evaluation of several exposure considerations. The first exclusion operates through a comparative analysis of the risk potential of the microbial pesticide whose pesticidal activities have been increased with the potential risk of the microorganism(s) from which it was derived. This comparison is conducted within the context of the area to which the microorganism or its genetic material may reasonably be expected to spread, and the likelihood of increased risks that may occur due to greater exposure potential because of increased host range, competitiveness, or survivability of the microbial pesticide, or because of increased genetic mobility. Consideration of these factors is intended to focus the evaluation on the potential for increased exposure of the microbial pesticide, its genetic material, or the products of the microorganism, to susceptible nontarget organisms. Increased competitiveness means the microbial pesticide is able to survive, reproduce and spread in the environment in a way that is more effective than its parental(s). For example, it would be able to increase its numbers at the expense of other organisms, or it would become established in a new niche thereby increasing opportunities for exposure. Either of these mechanisms implies that the microbial pesticide would be better suited to survive and expand its population and thus pose a greater potential risk to the environment relative to the parental organism(s). Similarly, greater survivability means the microbial pesticide persists longer than its progenitor(s) and, thus, there may be greater opportunities for exposures to nontarget organisms. Mobility refers to the horizontal movement of genetic material from the genome of one organism to the genome of another organism(s). The significance of genetic mobility depends on what material is moved and the nature of the recipient species. For example, if the mobility of a toxin gene is increased, the gene may be transferred to organisms where it did not exist previously and would not be expected to exist naturally. The result of this transfer may be to confer greater competitiveness or survivability on the recipient organism, and/or to allow the recipient to become established in a new niche, thereby increasing exposure to the toxin. The second exclusion considers similar exposure factors except that it specifically applies to microorganisms whose pesticidal activities are increased by movement to a new environment. It would apply to microbial pesticides arising from natural breeding and microorganisms selected from one environment for use in a new environment. Under the exclusion mechanisms, the researcher would consider the host of factors that may affect hazard and exposure to determine whether a test, in which the microorganism's pesticidal activity is increased, is eligible for exclusion from the notification requirement, with ``increased'' referring to an augmentation of the ability of the microorganism to act as a pesticide and the genetic material controlling these activities being part of the normal genetic complement of the species in nature. When pesticidal activity has been created, rather than increased, the resulting microbial pesticide would not be eligible for consideration under the exclusions. Under the exclusions of Option 3, the researcher would make an assessment of the potential risk of the test, considering variables such as environment, exposure, and toxicity or pathogenicity. If, for example, the test has confinement measures/features designed to control the movement of the microorganism, the effective ``test site environment,'' may be diminished. With sufficient confinement controls, the microorganism and its genetic material may only be reasonably expected to occur in the immediate test site and not disperse to any surrounding area. In this case, the immediate test site is the ``test site environment.'' As the effective test site environment is narrowed, the researcher's assessment of the interactions between the microorganism and the environment becomes simpler because opportunities for unintended exposures that may increase potential risks--resulting from an increased host range, competitiveness, survivability or genetic mobility--are reduced. Thus, the researcher's determination as to whether any particular test qualifies for an exclusion requires an assessment of the likelihood of an incremental increase in exposure in the test site environment taking into account the adequacy of the confinement measures. In order to determine whether a test is eligible for exclusion, a researcher would first make a determination of whether there is an increase in pesticidal activity (e.g., increased toxin production) of the microorganism, and then if there is an increase in environmental exposure (e.g., an expanded host range). If the answer is ``yes'' to both parts of these questions, then notification would be required because the test poses a potentially greater risk. When the answer to the question of whether the microbial pesticide has greater survivability is ``yes,'' the test would require notification, assuming an increase in pesticidal activities. Here, the evaluation may focus on the characteristics that give the microorganism a greater chance to live and reproduce, such as increased reproductive rate, greater temperature or pH tolerance, or better defense mechanisms against predators, when compared with the progenitor(s). The researcher must then consider whether these enhanced characteristics will actually increase exposure to nontarget organisms inside the test plot or outside the test plot given the test's confinement measures. If the answer is ``yes,'' notification to EPA is required. Another exposure element that must be considered by the researcher to determine if notification is necessary is host range, specifically whether the host range of the microorganism has increased relative to that of the progenitor(s) in the test site environment. Such an evaluation would focus on whether different or additional types of nontarget organisms would potentially be exposed and whether any of these nontargets are likely to be in or around the test site environment, as well as the potential for actual exposure taking into account the test's confinement measures. When the answer is ``yes,'' notification would be required for the test (again assuming an increase in pesticidal activities) because the relative risk of the microorganism in the test may have been increased. EPA anticipates that many microbial pesticides included under the initial scope of Option 3 would, through the exclusion mechanisms, be removed from the requirement of notifying EPA. However, because of the experiment-specific nature of the analysis involved in the exclusion mechanisms, it is not possible to indicate a priori which microbial pesticides would qualify for exclusion. 3. Comparison of the Options. A primary objective in designing and selecting a scope of coverage is to provide a risk-based approach to identify those microbial pesticides subject to notification to EPA. The three options discussed in this proposal offer different conceptual approaches to meet this objective. These conceptual differences lead to differences in the type and number of microbial pesticides covered by each option, and necessitate differences in implementation. EPA anticipates that the three options will require notification for many of the same microbial pesticides, although it may be that some of the microbial pesticides subject to notification under Options 1 and 2 will not require notification under Option 3. Conversely, some microbial pesticides covered by Option 3 may not be covered by Options 1 and 2. In order to illustrate the relative coverage of the options and the decision process for evaluating whether the tests are subject to notification, the examples discussed in Unit IV.B.1. of this preamble are analyzed below: \ It is anticipated that a microbial pesticide comprised of a microorganism functionally expressing the gene for a toxin from a parasitic wasp would be subject to notification under all three options (Example 1 in Unit IV.B.1. of this preamble). \ A microbial pesticide such as that discussed as Example 2 in Unit IV.B.1. of this preamble (wherein the active subunit of a toxic protein is coupled to another protein to enhance transport of the toxic moiety across membranes) would be covered under Option 1. It would be covered under Option 2 unless the sequence for the recognition subunit was from the same genome as the sequence for the toxic subunit. It would likely be covered under Option 3 if pesticidal activities were increased and there was a greater risk in the test site environment in terms of increased host range, competitiveness, survivability or genetic mobility compared to the microorganism from which it was derived. \ A microbial pesticide with changes in genes controlling host range specificity (Example 3 in Unit IV.B.1. of this preamble) would be covered under Option 1, if the change were to enhance pesticidal properties and involved the introduction of genetic material that had been deliberately modified. The pesticide in Example 3 probably would not, under Option 2, be subject to the notification requirement because most changes in host range currently result from deletions or rearrangements within a single genome. For Option 3, if the host range were increased, the microbial pesticide in Example 3 would likely be subject to the notification requirement. However, if the host range were decreased or shifted, the microbial pesticide would not be subject to the notification requirement, unless the shift resulted in an increase in infectivity, pathogenicity or virulence and there was a greater risk in the test site environment in terms of competitiveness, survivability, or genetic mobility. \ Example 4 in Unit IV.B.1 of this preamble discusses increases in the ability of the microorganism to survive. This example would be covered by Option 1 if the change were to enhance pesticidal properties through introduction of genetic material that had been deliberately modified. It might be subject to the notification requirement under Option 2 depending on whether the ability to better resist solar radiation was due to rearrangements or deletions in a single genome. It would be covered under Option 3 if the ability to better survive increased the ability of the microbial pesticide to act as a pathogen, and there was an increase in competitiveness, survivability, or genetic mobility. Options 1 and 2 can be considered more centralized decision-making approaches than Option 3, which would, in contrast, be considered a decentralized approach. For Options 1 and 2, EPA made a generic determination, based on its experience and general knowledge, that for certain categories of microbial pesticides it has sufficient information to determine that the probability of unreasonable adverse effects during small-scale testing is low. The Option 1 and 2 scope definitions are structured so that these categories of microbial pesticides fall outside the scope (i.e., they are not covered by the notification requirement). Other categories are within the scope, and are described by EPA in the Options 1 and 2 scope definitions. A centralized approach leads to greater consistency in decision-making. There is one standard--that provided by EPA. The researcher determines whether a notification is required for a test based on that standard, which does not require interpretation to be implemented. The potential for differing interpretations is limited because of the nature of the scope criteria. Option 3 shifts responsibility to the researcher for evaluating whether there is an increase in risk potential in a test, and whether there should be notification to EPA. This determination could be made without direct EPA involvement. Under Option 3, essentially all tests of indigenous microbial pesticides would be evaluated by the researcher, taking into account site-specific factors, to determine whether the Option 3 criteria have been met (i.e., whether there is an increase in risk potential for the specific test). The initial range of microbial pesticides in Option 3 is broadly defined as those developed by deliberate processes or techniques, including those with changes in genotype and those with changes in phenotypic expression resulting from environmental factors. It, thus, includes both naturally occurring microorganisms and microorganisms that have experienced deliberate genetic modification. Hence, the initial range, or the starting point, for Option 3 is far broader than for Options 1 and 2. The type and extent of evaluation or assessment researchers must make to determine whether notification to EPA is required for a microbial pesticide test also differs between Option 3 and the other two options. Options 1 and 2 present the researcher with a limited number of factors that must be evaluated to determine notification status. For example, under Option 1, the researcher would need to answer only the following questions: (1) Have pesticidal properties been affected; (2) has genetic material been introduced; and (3) has the introduced genetic material been modified? Under Option 1, notification to EPA is required if the answer is ``yes'' to all three questions. Option 2 uses an analogous approach. Option 3 may require the researcher to consider more factors, including a consideration of the test site environment and an analysis to determine whether the Option 3 criteria regarding hazard and exposure have been met. For example, to determine whether a microbial pesticide will potentially ``pose a greater risk, in the test site environment in terms of increased host range, competitiveness, survivability, or genetic mobility, compared to the microorganism(s) from which [it was] derived'' the researcher would evaluate such factors as the test site, including confinement measures; the range of nontarget organisms likely to be exposed; the mechanism(s) by which organisms may be adversely affected by the microbial pesticide; and specific differences in the microbial pesticide compared to the microorganism(s) from which it was derived. For this option, as with the other two options, if the researcher finds during an analysis of notification status that a particular consideration would exclude the test from the notification requirement, then no further assessment of other factors would be necessary. EPA, in devising Options 1 and 2, generically considered environmental risk issues in determining whether microbial pesticides should be subject to the notification requirement. Two issues that were given particular consideration are the probability that the microbial pesticides not subject to the notification requirement would be competitive enough to result in significant exposures beyond the test site environment, and whether nonsubject microbial pesticides would be likely to have greater survivability or genetic mobility compared to the organisms from which they were derived. The decentralized approach of Option 3 shifts the responsibility for evaluation of these factors, and, thus, the determination of the notification status of a small-scale test from EPA to the researcher. Each pesticide to be tested or each change in environment or set of environmental conditions requires the researcher to evaluate the test to determine whether it is within the initial scope established by Option 3, and whether it is eligible for exclusion from the notification requirement. A consideration of the factors laid out as relevant to Option 3 would be made on site by the researcher rather than by EPA. Another difference among the options is that the boundaries circumscribing the categories of microbial pesticides subject to notification are more dynamic and fluid in Option 3 than they are in Options 1 or 2. For example, Option 3 relies on the term ``new environment.'' The determination of what constitutes a ``new environment'' must be made on a case-by-case basis. The decentralized approach of Option 3 places greater responsibility on the researcher and can result in variations in decisions regarding the notification status of a test, as well as the need for confinement or other measures. There are also differences between the options in terms of which types of microbial behavior are considered to raise hazard concerns meriting evaluation, with Option 3 covering a subset of the hazard endpoints addressed by Options 1 and 2. Option 3 only addresses the hazard endpoints associated with the creation or increase of toxin production, pathogenicity, infectivity, or virulence. Thus, Option 3 does not address hazard endpoints resulting from other mechanisms by which risk potentially can be presented. For example, Option 3 does not address the potential risks presented by competitive displacement. The narrower hazard focus of Option 3 is premised on the argument that the likelihood of significant environmental harm from competitive displacement is low for small-scale tests and therefore, microbial pesticides that act through this mechanism should not be subject to the notification requirement. Other mechanisms by which microorganisms exert adverse effects, such as the immobilization of substances important to other organisms, production of substances (e.g., lactic acid) that inhibit or repel other organisms, predation and some forms of parasitism, would not be covered by Option 3. One of the goals of this rulemaking is to create a system which could accommodate advances in the understanding of the hazards and exposures of microbial pesticides. All three options were crafted to achieve this goal. However, they differ in how they would achieve it. Options 1 and 2, which are centralized options, provide a means by which information would be transmitted to EPA, which would then use this information in evaluating notifications as discussed in Unit III.B. of this preamble, establishing exemptions (Unit V.B. of this preamble), or ultimately as a basis for changing scope of coverage. Option 3, the decentralized option, places on the researcher the responsibility of determining whether notification to EPA is necessary for a particular experiment. As the researcher gains information on potential risks, this information will be reflected in the specific determinations performed by that researcher. To the extent the researcher shares information with other researchers (e.g., publication in scientific journals), information concerning the potential for risk associated with specific types of tests could be disseminated to a wider community. 4. Implementation. The first three sections of Unit IV.B. of this preamble describe three approaches, Options 1, 2 and 3, for defining the scope of microbial pesticides to be subject to notification. In order to function in a regulatory context, each option must be implemented with the appropriate procedures to create equitable, accountable, consistent oversight that fulfills the goals of the regulation. This section identifies and discusses the use of four separate implementation procedures, and their utility, cost, and relevance for each option. The four procedures are: (1) Guidance from EPA on the considerations used in making a determination of whether a microorganism is covered by the scope; (2) documentation of the determination; (3) review of the determination by a third party; and, (4) retention of the records of the determination. ``Guidance from the Agency'' could consist of a ``points to consider'' document describing appropriate issues to consider before arriving at a determination. ``Documentation of the determination'' is a written account of the considerations evaluated in making the determination of whether a microorganism is covered by the scope, the conclusions of the evaluation, and how the conclusions were reached. ``Retention of the documentation'' addresses where, and for how long, documentation of the determination will be maintained. ``Third party review of the determination'' involves a review of the determination by a party other than the individual or group conducting the research activity. Both Options 1 and 2 are crafted such that the researcher would consider a limited number of simply addressable factors, answerable with a ``yes'' or ``no,'' to determine whether the notification requirement applies. The answers to the questions posed are readily apparent and would normally be part of the researcher's test protocols and records. Therefore, to determine whether a test would be subject to notification, researchers would look to their laboratory notebooks. For most of the considerations, the answers are relatively straightforward. For example, in Option 1, one of the key considerations is whether genetic material has been introduced. The determination can be made relatively simply since the test protocol either involves introduction of genetic material or does not. Option 3 may require the researcher to consider a broader range of factors than the other options, including a consideration of the specific environment in which the test would take place, and requires individual researchers to judge whether their tests are excluded from the notification requirement. Although Option 3 may, in some cases, increase the burden on the researcher by requiring the consideration of a broader range of factors, it may also allow a broader range of tests to be excluded from the notification requirement. As with Options 1 and 2, researchers may not need to evaluate every factor before determining that a test is excluded from the notification requirement. In some instances under all the options, the decision could be made early in the evaluation process without EPA's involvement. An additional consideration has a bearing on the implementation of Option 3--exclusion/inclusion of a specific microbial pesticide is substantially influenced by the individual judgment of the researcher. Although the qualifications and experience of researchers may vary, Option 3 is based on the premise that the individual or institution conducting the research is in the best position to make the required judgments concerning the potential risks associated with a specific test. As in Options 1 and 2, researchers must ultimately answer a series of ``yes'' or ``no'' questions; however, Option 3 may require researchers to consider other factors--not just material within their laboratory notebooks--in order to support their conclusions. Although Option 2 may, in some cases, increase the burden on the researcher by requiring the consideration of a broader range of factors, by taking a broader range of factors (including site-specific factors) into account, it may provide the opportunity for a broader range of tests to be excluded. Under FIFRA, the Agency must structure its regulatory program so that use of the microbial pesticides excluded from the notification requirement is unlikely to pose unreasonable adverse effects on human health and the environment. To meet this requirement, EPA, in determining what will be subject to the notification requirements and what will not, balances risks and benefits. When the potential benefits of the test outweigh the potential risks, the no-unreasonable-adverse-effects standard imposed by FIFRA has been attained. Therefore, the Agency must structure its program so that the risk determinations for anything excluded from the notification requirement, whether made by the Agency or the researcher, will support a risk/benefit balancing where the benefits outweigh the risks. Within this risk/benefit framework, EPA must make an initial determination to identify the types of microbial pesticides it believes warrant exclusion from notification. Because Options 1 and 2 identify specific categories of microbial pesticides, EPA would be relying on its own assessment of risks and benefits to exclude those microbial pesticides not within the scope of Options 1 and 2 from the notification requirement. Option 3 lays out an experiment-specific framework that places more responsibility with the researcher for determining whether the experiment is eligible for exclusion based on an assessment of risk. For Option 3, EPA would be relying on several factors in order to conclude that those experiments eligible for exclusion do not pose unreasonable adverse effects. These factors include: (1) The nature of the experiments (limited field tests); (2) the availability of appropriate guidance for researchers, (3); the traditional care taken in research; and (4) the potential liability to researchers and institutions. As discussed below, EPA believes that, in light of the discretion afforded the researcher under Option 2, Agency guidance will be an important part of the regulatory structure for this option. For the same reason, the Agency also believes that third party review of the determination is necessary under Option 2. EPA requests comment on this approach. EPA also requests comment on whether and how the following mechanisms could be used in Option 3: (1) Documentation of the determination; and (2) retention of the documentation for a specific period of time following review. EPA also requests comment on the need for any or all of the four implementation mechanisms for Options 1 and 2 (See Unit VIII.B. of this preamble). The following paragraphs discuss EPA's current thinking on the applicability and utility of the four implementation procedures as they relate to the three options. With regard to guidance provided by the Agency, for Options 1 and 2, EPA believes that the determination of notification status is relatively straightforward, and the selection criteria set forth in the scope definitions provide sufficient guidance from the Agency. No additional guidance is needed. Option 3 involves consideration of a larger number of factors in determining whether notification is required. As a result, EPA believes there is a greater potential for inconsistency among researchers in the interpretation of this option than for Options 1 and 2. To address this possibility, Agency guidance becomes a more important component of the regulatory approach. EPA anticipates such guidance would be based on the considerations identified in the ``Exercise of Federal Oversight Within Scope of Statutory Authority'' published in the February 27, 1992 Federal Register. In regard to review by a third party, there may be two types of benefits associated with this implementation component. First, independent reviewers may have experience and perspectives that complement and extend the experience and perspectives of the researcher, thereby improving the evaluation. Second, the use of independent reviewers will help provide consistency to the whole program and help ensure that individual decisions fall within mainstream thinking in the scientific community. Third party review could be performed by a local review group, composed of individuals with expertise in, for example, microbial ecology, molecular biology, human health, community and systems ecology, and toxicology. The third party could be similar to, or could actually be, the Institutional Biosafety Committees (IBCs) described in the National Institutes of Health (NIH) ``Guidelines for Research Involving Recombinant DNA Molecules'' (51 FR 16958, May 7, 1986), or some other responsible group or individual(s) in the research organization. Alternatively, the researcher could request that EPA serve as the third party reviewer. Some small scale experiments involving microbial pesticides are currently being reviewed, either voluntarily or through the specific requirements of mechanisms such as the NIH Guidelines, by a third party within the researcher's specific institutional setting. Because of the nature of Options 1 and 2, EPA does not believe that an EPA requirement for third party review is generally necessary. However, because of the breadth of factors to be weighed under Option 3, EPA currently believes that third party review of the researcher's determination that a microbial pesticide is not subject to the notification requirement may be appropriate, and is interested in comments on this issue. In terms of documentation of the decision, notebooks and test protocols would contain the information to support a determination under Options 1 and 2. Thus, for these options the documentation already routinely part of the research is adequate. Option 3 presents a different situation, since some of the information used in the determination would not likely be maintained as a matter of course in researchers' notebooks and test protocols. Given the availability of appropriate Agency guidance and the conditions under which research is typically developed and performed, it is likely that the appropriate factors will be considered. The Agency requests comment, however, on whether researchers should write down the key points of their analyses, to show that the relevant considerations have been evaluated and appropriate choices made. In terms of retention of records, many researchers would ordinarily maintain the necessary documentation as part of the records of the research activities. However, when the information important to the risk analysis is not a part of the research protocol, or ordinarily considered by the researcher, there may be a need to go to other sources to obtain the information. While researchers usually retain their laboratory notebooks for many years, this may not be true for the additional information gathered for the risk analysis required under Option 3. EPA requests comment on whether it would be appropriate to establish a period of time (perhaps 3 years) during which these records should be maintained. A related issue is who would retain the records once they are compiled and reviewed. The documentation could be maintained by the individual or group that made the initial determination, or reviewer(s) of that material. 5. Microbial Pesticides Covered by Current Notification Policy but not Covered by the Option. Since 1984, EPA has had in place policies that require notification to EPA for small-scale testing of all genetically altered and nonindigenous microbial pesticides. For the purposes of this rule EPA is using the definition of ``nonindigenous'' published in the 1986 ``Coordinated Framework for the Regulation of Biotechnology'' (51 FR 23302, June 26, 1986), which stated that a microorganism would be considered to be nonindigenous to ``any one of the geographic areas listed below if it is isolated from outside that area: (1) The continental United States, including Alaska, and the immediately adjoining countries; (2) the Hawaiian Islands; (3) the Caribbean Islands including Puerto Rico and the U.S. Virgin Islands.'' Some of the microbial pesticides covered by the 1984 and 1986 policy statement would no longer be subject to the notification requirement, should this proposal become a final rule. Under Options 1 and 2, two groups of microbial pesticides would no longer be subject to the notification requirement. These are: (1) Naturally occurring nonindigenous microbial pesticides; and (2) all microbial pesticides that have been genetically altered (whether they are indigenous or nonindigenous), but that do not fall within the scope of Options 1 or 2. Naturally occurring nonindigenous microbial pesticides would also be excluded from Option 3. Because of the nature of Option 3, EPA cannot a priori determine which other microbial pesticides currently covered by the 1984 Interim Policy Statement would no longer be subject to the notification requirement, should Option 3 become the scope of a final rule. Moreover, because Option 3 has a broad initial scope, some microbial pesticides that were not included in the 1984 scope would be initially captured under this option (e.g., some naturally occurring), although many of these microbial pesticides might be eligible for the exclusions of Option 3. Some genetically altered microbial pesticides would also be captured within the initial scope, although many of these would also be eligible for exclusion. Those pesticides EPA would exempt from the notification requirement, under the authority of FIFRA section 25(b), would be exempted because EPA has determined them to be adequately regulated by another Federal agency, or to be of a nature as to not require regulation. For naturally occurring nonindigenous microbial pesticides used at small-scale, the Agency believes adverse effects are most likely to occur in the areas of animal or plant pathogenicity or human health. Nonindigenous microorganisms that may have plant pest or adverse animal health effects are regulated by the Animal and Plant Health Inspection Service (APHIS). Under its own authority, and pursuant to its responsibilities under the National Environmental Policy Act (NEPA), 42 U.S.C. 4321 et seq., APHIS considers the human health and environmental impacts associated with nonindigenous microorganisms that are potential plant or animal pests. In recent years, the Agency has worked closely with APHIS in the review of nonindigenous microbial pesticides. The Agency believes that small-scale tests involving nonindigenous microbial pesticides, favorably acted upon by APHIS (i.e., granted a permit or determined that a permit is unnecessary), are unlikely to cause any significant impact on the environment. Another measure of oversight is provided by the U.S. Public Health Service, which regulates the importation and subsequent distribution of microorganisms that are of human health concern. EPA believes that it should review, prior to environmental release, nonindigenous microbial pesticides that pose a potential for significant risk to human health or the environment when used in testing at small-scale, that are not otherwise reviewed by another Federal agency, provided that a category of such microorganisms can be identified. However, the Agency is not aware of the existence of such a category of nonindigenous microbial pesticides and believes that continued imposition of the notification requirement for all nonindigenous microbial pesticides would constitute unnecessary duplicative oversight of research and development of these products. Thus, the Agency believes that review by EPA is unnecessary at this stage and is, therefore, willing to presume that small-scale tests with such naturally occurring nonindigenous microbial pesticides would not present an unreasonable adverse effect and would not require an EUP under FIFRA. Hence, the Agency proposes not to require notifications for these microbial pesticides. Indigenous microbial pesticides that do not otherwise fall within the scope of Options 1 and 2 would no longer be subject to the notification requirement. EPA judges these microbial pesticides to be less likely to pose significant risks to human health or the environment when applied in small-scale tests than those that would be covered under the options. In arriving at this conclusion, the Agency has taken into account its experience with naturally occurring microbial pesticides, and those altered by both classical and newer genetic techniques that would be similar to naturally occurring microbial pesticides. EPA particularly draws upon its experience since 1984 with the assessment of these types of microbial pesticide products at the small-scale testing stage. Therefore, under the conditions discussed for each option, the Agency is willing to presume that small-scale tests of microbial pesticides containing microorganisms other than those in the scope definitions do not need EUPs, and is proposing that these microbial pesticides not be subject to a notification requirement. V. Other Provisions A. Testing in Contained Facilities For any scope option, it is important to clearly distinguish circumstances where testing of those microbial pesticides otherwise within the scope would not be subject to notification. One such circumstance is testing within a contained facility, such as a laboratory or greenhouse, where appropriate containment procedures and controls are employed. EPA does not propose to require notification for testing occurring in such facilities, because it does not believe such testing raises sufficient risk concerns that notification is warranted. However, excluding testing in contained facilities raises the need to describe what constitutes a contained facility where appropriate containment procedures and controls are employed. One alternative would be to set a single standard with specific containment parameters for all microbial pesticides. Another approach would be to identify several increasingly stringent levels of containment and issue guidance on how the various microbial pesticides would be matched to the appropriate level of containment. Both of these approaches could be complex and unwieldy for EPA to develop and implement. Because of their prescriptive nature, such approaches would reduce the Agency's and the researcher's flexibility in defining appropriate containment for specific testing, and could result in EPA regulating based on a rigid standard rather than exempting the research. Each change in a prescriptive standard would have to be incorporated into the standard through rule amendments or variance procedures. EPA has chosen, therefore, to propose a ``performance standard'' to establish the boundary between research conducted in a contained facility and other testing. Under this proposal, the individual or institution conducting the testing is given the discretion to select and use procedures and controls appropriate to achieve adequate containment and inactivation in light of the characteristics of the microorganism being tested. These methods and controls would take into account the microorganism's ability to survive in the environment, potential routes of release, procedures for transfer of materials, and plans for routine and emergency clean-up and test termination. Under this performance standard, EPA would not establish a rigid prescriptive approach on how containment and inactivation are to be achieved, but would reserve the right to judge whether the selected controls are adequate to prevent unreasonable adverse effects. EPA's approach accepts, in this instance, the judgment of the individual or institution conducting the research, which EPA would not generally question. The approach recognizes that many different kinds of microorganisms displaying a wide range of characteristics could be used in research, and that a single containment standard may not be appropriate for all. For example, for certain microorganisms, emanation of small numbers of viable microorganisms could be of concern, while emanation of large quantities of other microorganisms would not. The approach also recognizes that the type of containment or inactivation controls (e.g., procedural, mechanical, and/or engineering) appropriate for one microorganism might have limited relevance to other microorganisms. EPA expects that the researcher will be cognizant of these factors when selecting controls appropriate to the microorganisms being studied. In addition, the researcher may choose to refer to existing standards such as the containment levels described in Appendix G of the National Institutes of Health (NIH) ``Guidelines for Research Involving Recombinant DNA Molecules'' (51 FR 16958, May 7, 1986). This proposed approach would enable EPA to review and evaluate the control measures, although the Agency does not anticipate such reviews becoming routine. In the limited number of instances where EPA does request to review the control measures, and as a result of that review determines that further action is called for to prevent unreasonable adverse effects, the proposal provides a flexible range of options that the Agency can use depending upon the specific situation. For example, in instances where improvement in containment is advisable, but there is no immediate problem, the Agency could recommend modifications to controls for future tests. Where a problem needs to be addressed in the current test, the Agency could request that the modifications be made immediately. Failure to comply with EPA's request would result in revocation of the exemption from the requirement to submit a notification. A performance standard approach such as that outlined above may be questioned as being somewhat ``vague,'' and therefore not having much regulatory utility. EPA believes that the standard provided is sufficiently clear for its intended purpose, while providing flexibility and discretion to the researcher. EPA believes this less prescriptive, performance standard approach is less burdensome than other alternative approaches to defining what constitutes a contained facility, while still meeting the objective of ensuring adequate containment. The Agency is also considering whether minimal recordkeeping to document the selection and use of the containment and inactivation controls should be required for eligibility for the exemption. Specifically, EPA is considering whether 172.45(e)(2) should be modified and 172.45(e)(3) should be added as follows: (2) The selection of containment and inactivation controls shall be approved in writing by an authorized official of the organization that is conducting the test prior to commencement of the test. (3) Records shall be maintained describing the selection and use of the containment and inactivation controls that will be used during the test. These records shall be made available, upon request, for inspection at the test facility. In addition, these records shall be submitted to EPA at the EPA's written request and within the timeframe specified in EPA's request. Under such an option, the individual or institution would maintain records demonstrating that the choices made were appropriate for ensuring the testing is adequately contained. The type of information that would be in these records would include: An identification of the microorganism, a description of the containment and inactivation measures selected, and a brief statement of why these measures were selected. The controls selected could be indicated by a simple reference to existing standards, such as the containment levels described in the NIH Guidelines. Such a proposal would require the researcher to keep records showing adequate containment, but would allow the researcher flexibility to decide what specific records should be kept. Those people who favor a recordkeeping provision believe it need not be overly burdensome nor require a significant change in the activities of researchers. Recordkeeping is currently an accepted standard practice among those conducting research in contained facilities under the NIH Guidelines. In most cases, laboratory notebooks normally kept in the course of research should contain the information that would be required by this provision. The level of recordkeeping to document the use of the controls selected for containment and inactivation would be at the discretion of the researcher. The extent of recordkeeping would be correlated with the characteristics of the microorganism and standard practices employed to address concerns. Thus, documentation could range from identification of routine standard operating procedures, to specific notations in laboratory notebooks, to daily log entries for microorganisms that present the greatest concerns. Others believe that records showing adequate containment was selected and employed are unnecessary, because the probability that microbial pesticides released from laboratories or greenhouses would subsequently establish in the environment in a manner harmful to humans or the environment is so low that the additional burden of a recordkeeping requirement is not warranted. They believe recordkeeping may increase the costs of research, and place a requirement on those who are supposed to be exempt under this proposal. They also believe it to be inconsistent with the rest of EPA's proposal which reduces burden and provides regulatory relief. These opponents would argue that the recordkeeping requirement by its existence increases the Federal presence in the laboratory, even if EPA does not routinely inspect the records, and this may be a disincentive to researchers. Finally, they question whether EPA should spend its limited resources determining if records have been kept; rather, they assert higher priority risk considerations should be the focus of EPA's efforts. EPA is requesting comment on these issues and the merits of its proposed approach on containment in Unit VIII.D. of this preamble. In addition, the Agency is requesting comment on whether minimal recordkeeping to document the selection and use of the containment and inactivation controls should be a required element for the exemption. B. Exemptions from the Notification Requirement The Agency has included in the proposal at 172.52, a mechanism for exempting, as information warranting such action becomes available, certain subgroups of microbial pesticides from the notification requirement. This provision allows EPA, on its own or in response to a petition, to initiate rulemaking to exempt a specific individual microbial pesticide or a class of microbial pesticides from the notification requirement. The exemption, which could be used in conjunction with any of the three options, would be based on supporting information that would allow the Agency to conclude that the microbial pesticide would not pose unreasonable adverse effects to human health or the environment. This provision was part of the January 1989 draft; no adverse comments were received on this provision. VI. Summary and Findings EPA has reviewed various possibilities for addressing small-scale testing of microbial pesticides, and has concluded that the regulatory scheme included in this proposal is adequate to protect human health and the environment from unreasonable adverse effects. In arriving at this conclusion, EPA has taken into account its interactions with other Federal agencies, comments received from various sectors, and its own experiences with risk issues associated with microbial pesticides, particularly its experiences since 1984 with reviewing small-scale tests using microbial pesticides. The Agency has also been mindful of the potential in this area for the development of generally safer, more beneficial pesticides, and the need to strike ``a balance between facilitating--or, at a minimum, not unduly impeding--pesticide research and development and protecting against human and environmental injury'' (39 FR 11306, March 27, 1974). Perhaps the most critical factor in the Agency's decisionmaking process is the selection of an appropriate scope of coverage. All three scope options address issues likely to be relevant to small-scale use of microbial pesticides; however, the options differ in the breadth of microbial pesticides covered with regard to the starting point for analysis, the kinds of risk issues addressed, the extent of site-specific analysis, who performs the analysis, and the extent to which additional measures may be necessary for consistent, effective implementation. EPA believes that while Options 1 and 3 provide risk-based definitions for the scope of coverage, each accomplishes the goal of identifying subject microbial pesticides in a different way. Option 1 incorporates an inclusionary definition that is designed to minimize regulatory burden by directly identifying the specific microbial pesticides covered by the regulation. It has the highest degree of regulatory clarity, and thus, is more easily understood and used by the researcher (or research institution) and EPA. Moreover, because the majority of the analysis to determine whether notification is required has been made by EPA, Option 1 requires less analysis by the researcher and fewer measures to ensure effective implementation. Options 2 and 3 are exclusionary definitions in that they provide broad general definitions that are subsequently narrowed by exclusions. These are in turn modified by explanatory footnotes to provide the necessary specificity for regulatory use. EPA is concerned that these options may introduce various degrees of complexity that could render the regulation more difficult to interpret, understand, and use than would be the case with Option 1. This complexity could ultimately result in both the Agency and the regulated community expending valuable resources to clarify whether a given microbial pesticide is within the scope. In particular, Option 3 involves site-specific analysis by the researcher to determine notification status and the Agency believes that procedure may be associated with relatively higher cost and effort relative to either Option 1 or 2. However, by taking a broader range of factors (including site-specific factors) into account, Option 2 may provide the opportunity for a broader range of tests to be excluded from the notification requirement. EPA believes that satisfaction of the unreasonable adverse effects criterion for Options 1 and 2 can be achieved without requiring additional implementation procedures. However, for Option 3, the Agency currently believes that a determination of no-unreasonable-adverse-effects should be premised on inclusion of specific implementation procedures, specifically guidance to researchers and third party review, to assure the adequacy of the decision on the notification status of the microbial pesticide. Considering all factors, including the four priniciples enunciated in the ``Report on National Biotechnology Policy,'' the FIFRA SAP and BSAC recommendations and public comments, EPA prefers Option 1. The Agency believes Option 1 identifies the appropriate microbial pesticides for notification, most reduces the burden for the researcher, and has the highest degree of effective regulatory utility. The proposed regulatory scheme includes specific procedures to be followed by EPA and submitters in order to facilitate an expeditious and effective screening process. Similarly, flexible data requirements are included to provide the information necessary for the Agency to review the proposed testing. EPA believes that, taken together, the proposed scope of coverage, procedures, and data requirements are sufficient to allow the Agency to screen small-scale testing of microbial pesticides in a manner that will adequately protect human health and the environment. Therefore, experimental use of microbial pesticides as described in this proposal will not pose unreasonable adverse effects. Finally, in order to reduce the regulatory burden at this stage of pesticide development, the proposal contains several provisions for exempting certain microbial pesticides from review, including an exemption mechanism that would allow the Agency to further reduce the scope of coverage at a later date. EPA continues to believe that small-scale tests of microbial pesticides adequately contained in research facilities are unlikely to pose unreasonable adverse effects to human health or the environment, and therefore do not warrant review. EPA also believes that it should not continue to review small-scale use of nonindigenous microbial pesticides, not otherwise captured within the scope, since at this time EPA has not been able to identify any pesticides in this category that raise risk concerns that are not already being reviewed by other Federal agencies. Therefore, EPA believes that the risk/benefit analysis for these pesticides results in a conclusion that use of them is unlikely to cause unreasonable adverse effects. VII. Statutory and Other External Review A. EPA Biotechnology Science Advisory Committee The BSAC met on September 7, 1990, to review and comment on the issue of scope of coverage of microbial pesticides for notification before small-scale testing. The BSAC was provided with an issue paper that presented and described two scope definitions. After reviewing the two scope definitions, the BSAC developed, with annotation, the following definition for the Agency's consideration: ``Microbial pesticidesThe Subcommittee suggests EPA should add a footnote referring to active ingredients. [Note: Specifically, the Subcommittee wished to ensure that consideration of microbial pesticides included both the active ingredients and any inerts.] whose pesticidal properties have been imparted, enhanced, or modified by alteration of the genome would be subject to oversight before small-scale testing, with the exception of: 1. Microorganisms modified solely: (a) Through chemical and physical mutagenesis; (b) by movement of nucleic acids using the physiological processes``By physiological processes'' means there has been no directed addition to, rearrangement of, or removal of nucleic acids from the nucleotide sequences that are introduced.of transduction or conjugation; (c) by movement of nucleic acids by transformation between organisms that engage in natural exchange;The Agency should develop a definition specifically addressing physiological processes as applied to transformation such that only transformations between microorganisms that exchange genetic material in nature are excluded.(d) by plasmid loss or spontaneous deletion; and (e) by anastomosis. 2. Microorganisms modified solely by point mutations, deletions, or rearrangements of sequences (i.e., translocation and inversions) within a single genome,A ``single genome'' means the genome of a single isolate or a single strain, or a single species with ``species'' defined as organisms sharing a certain (to be defined) percentage of DNA relatedness as demonstrated under supra-optimal conditions for DNA reassociation.including its extrachromosomal elements. 3. Microorganisms modified as in 1 or 2 above that also have been modified by the introduction of noncoding, nonexpressed nucleotide sequences that cause no phenotypic or physiological changes in the recipient microorganism.''``Noncoding, nonexpressed nucleotide sequences that cause no phenotypic or physiological changes in the recipient microorganism'' means sequences not involved in gene expression or replication. The BSAC recommended this scope of coverage in their final report dated November 14, 1990. EPA Response: The Agency has not provided this specific definition as an option for discussion in this preamble because it is encompassed by Options 1 and 2. Several of the BSAC's specific recommendations have been incorporated in drafting Options 1 and 2. B. FIFRA Scientific Advisory Panel Pursuant to section 25 of FIFRA, a Subpanel of the FIFRA SAP reviewed drafts of these proposed part 172 regulations in public meetings held November 22, 1988, and September 26, 1990. In 1988, the Subpanel agreed with the Agency's overall intent in revising 40 CFR part 172, but believed it was premature to codify, at that time, the scope of microbial pesticides to be subject to notification at the small-scale testing stage. The Subpanel believed that EPA oversight should continue under the existing 1984 and 1986 policy statements until after the Agency had the opportunity to consider the reports under development at that time by the NAS and the ESA. The NAS and ESA reports were to address criteria for the assessment of potential impacts related to the release of genetically modified microorganisms. These reports have now been published, and the Agency has considered them in developing this proposed rule. In its final written report (November 1988), the Subpanel also made several specific recommendations on the 1988 draft proposed regulation. These recommendations, together with the Agency's response, are available in the public docket. Subsequently, the Subpanel reviewed and commented on a draft proposal (dated September 4, 1990) and an addendum which together outlined three approaches for defining the scope of coverage for microbial pesticides. The September 1990 draft proposal contained the same two definitions of scope reviewed by the BSAC and the addendum contained the scope language developed by the BSAC as presented above in section A of this Unit. In its final report (dated October 9, 1990), the Subpanel strongly supported the timely promulgation of part 172, and noted that EPA's leadership in this area is ``important to bring focus to this topic for the benefit of industry, government and public-interest groups.'' The SAP Subpanel also made several specific recommendations which are discussed below, together with the Agency's response. 1. With regard to the three scope definitions, the Subpanel concluded that the proposals now embodied in Options 1 and 2, as well as the BSAC attempt to merge the two into a single approach, were all potentially acceptable. However, the majority of the Subpanel preferred the scope embodied by Option 1. The Subpanel explained their preference as follows: ``(i) This is the clearest statement defining the group of microbial pesticides that require oversight, (ii) it defines a slightly more appropriate group for oversight than Option 2 or the BSAC approach by including organisms that contain certain deletions, (iii) it is risk-based and focuses on the qualities of the product, and (iv) it appears to allow less opportunity for unintended gaps in oversight.'' Finally, the Subpanel recommended that the notification requirement should include organisms containing any introduced nucleotide sequences produced by restriction enzymes. EPA Response: Each of the scope alternatives reviewed by the SAP (Options 1 and 2) offers certain advantages and disadvantages. EPA agrees with the Subpanel's recommendation and believes that on balance, Option 1 comes the closest to meeting the Agency's requirements for regulatory clarity and scientific soundness. 2. The Subpanel stated that because some deletions may lead to large alterations in virulence and/or in host range, host-associated microbial pesticides obtained by deletion should not be exempted from notification before small-scale testing. EPA Response: With respect to coverage of microbial pesticides obtained by deletion, the Agency agrees (See Unit IV.B.1. of this preamble) with the Subpanel that certain deletions or rearrangements of genetic material within a single genome could impart or enhance characteristics of potential concern (e.g., expanded host range or virulence). Option 1 has been developed to include these microbial pesticides for coverage. However, as noted by the Subpanel, the long-term survival and/or competitiveness of these kinds of organisms may be compromised by the modification. Therefore, one could argue that they may not warrant notification before small-scale testing. The Agency has requested comment (See Unit VIII.G. of this preamble) on excluding some or all of these microorganisms from coverage at the small-scale testing stage. 3. The Subpanel recommended that coverage should include those situations where there has been directed addition to, rearrangement of, or removal of nucleic acids from the nucleotide sequences that are introduced into a microbial pesticide regardless of how the genetic material is introduced into the recipient microorganism. EPA Response: EPA agrees with the Subpanel's suggestion, and Options 1 and 2 have been developed to be consistent with this recommendation. 4. The Subpanel suggested that for a claim of natural genetic exchange to be acceptable, the exchange must occur under physical/chemical conditions typical of the organism's natural habitat and that the recipient organism and the organism that is the source of the DNA must coexist in the same habitat in nature. In addition, the Subpanel concluded that claims of natural genetic exchange and anastomosis made for the purpose of the scope definition must be evaluated within the context of the natural frequency of these events, so as not to include those that occur only very rarely, and when the microorganisms are kept under stringent selection conditions. EPA Response: The Agency agrees with the Subpanel's recommendation concerning clarification of the term ``natural exchange.'' To achieve the intent of this recommendation, the Agency has developed Option 2 such that the movement of nucleic acids by physiological processes is limited by three conditions: Recipient microorganisms must not have lost their ability to recognize and cleave foreign genetic material; must not have been exposed to conditions to induce competence artificially; and the nucleotide sequences that are moved must not have been altered. 5. With regard to the BSAC comments on the issue of scope (See Unit VII.A. of this preamble), the Subpanel recommended that the definition of a single genome be restricted to a single strain. They did not believe it should be broadened to encompass a species concept for the definition. EPA Response: EPA agrees with the Subpanel's recommendation on the definition of a single genome. The Agency believes that a broader definition could possibly allow for the exclusion of microbial pesticides that warrant coverage before small-scale testing. In addition, a definition of genome based on ``percentage of DNA relatedness as demonstrated under supraoptimal conditions for DNA reassociation'' would be difficult and costly to implement. As a result, genome is defined in Option 2 as the ``sum total of chromosomal and extrachromosomal genetic material of an isolate and any descendants derived under axenic culture conditions from that isolate.'' This focus of attention on the strain, as defined above, recognizes the differences in risk potentials that may exist between strains of the same species, and is also consistent with the manner in which microbial pesticides are handled under FIFRA for the purpose of pesticide product registration. 6. The Subpanel noted that the ``environmental release of microbial pesticides could be made more acceptable if the organisms were engineered with unique genetic markers that enable their detection to a high level of sensitivity in the environment and, where possible, selection from the population of ambient organisms.'' The Subpanel recommended that EPA consider requiring such markers for microbial pesticides to be used in small-scale field tests. EPA Response: The Agency acknowledges the benefits that could accrue from requiring that certain microbial pesticides be engineered with unique genetic markers, and has carefully considered including such a requirement in this proposal. The Agency believes that there may be instances where compliance with such a requirement could pose technical difficulties that outweigh the benefits of having the microbial pesticide so marked. The draft proposal reviewed by the Subpanel already contained the requirement for specific identification and detection of the microbial pesticide using sensitive detection methods. The Agency has added language in this proposal at 172.48 to encourage researchers to mark their microbial pesticides with unique genetic markers that enable sensitive identification in the environment. The Agency may require such markers on a case-specific basis. 7. In response to an EPA question, the Subpanel indicated that the data and information EPA proposes to require to support an assessment (as specified in the September 1990 draft) were appropriate, and offered two additional suggestions. First, the Subpanel suggested it would be useful to have an explicit statement calling for a literature review of information available on relevant aspects of the ecology and biology of the parent organisms. Second, the Subpanel suggested that EPA review the USDA's Agricultural Biotechnology Research Advisory Committee (ABRAC) guidelines and establish as much consistency as possible. EPA Response: With regard to the first suggestion, the Agency has included language at 172.48 of this proposal concerning the need to provide information on relevant aspects of the ecology and biology of the parent organism(s). Concerning the second suggestion, the Agency agrees that consistency among Federal agencies is desirable and is working with other agencies to achieve the consistency attainable in light of the various statutes and guidelines used to oversee biotechnology products. 8. The Subpanel noted that responsibility for oversight of the introduction into the environment of potentially harmful microbiological agents is split among several Federal agencies, particularly EPA and USDA. Therefore, the Subpanel recommended that EPA, along with the other appropriate regulatory agencies, adopt a more formal mechanism to ensure close coordination of the agencies and to avoid gaps in regulatory coverage. EPA Response: The Agency believes that coordination among Federal agencies for the review and approval of small-scale testing has been efficient and successful thus far. However, EPA agrees that a more formal mechanism for coordination may be appropriate and has initiated work with the appropriate groups to develop such a coordination. C. U.S. Congress and U.S. Department of Agriculture In accordance with FIFRA section 25, a draft of this proposed regulation was submitted in June 1988 to the U.S. Congress and USDA. USDA provided written comments on that draft in September 1988. These comments, together with the Agency's response, are available in the public docket. In July 1991, a second draft of the proposed regulation (dated June 28, 1991) was submitted to the U.S. Congress and USDA. USDA provided written comments on that draft on November 1, 1991. USDA strongly supported ``EPA's intent to eliminate any unnecessary burden on research activity which could impede the development of useful alternative pesticide products,'' commended the Agency for defining, in Options 1 and 2, a risk-based scope of organisms to be covered, and agreed with EPA that scope Option 1 is preferable for use under FIFRA. USDA also agreed that EPA should review, prior to small-scale testing, those nonindigenous microbial pesticides that may pose a potential for significant risk to human health or the environment that are not otherwise reviewed by another Federal agency, provided that a category of such microorganisms can be identified. In its comments, USDA indicated that it was not aware of any such category of microorganisms. USDA also provided several specific suggestions which are discussed below, together with the Agency's response. 1. USDA indicated that some of the discussion in the preamble could be interpreted to suggest that EPA believes that high risks are routinely associated with testing microbial pesticides. Understanding that this is not EPA's position, USDA suggested several editorial changes to reflect more accurately EPA's position. USDA also stated that it would be helpful to include in the preamble a more complete presentation of the potential risks to be addressed by the notification scheme as well as an indication of which risk concerns are addressed by other Federal authorities. EPA Response: EPA believes that testing with microbial pesticides will not routinely pose high risks to human health or the environment and the preamble has been modified as recommended. EPA agrees that it is important to provide a discussion of the kinds of concerns to be addressed by the notification scheme. The Agency has chosen to discuss this area in the context of the analysis of the options for scope of microorganisms to be subject to notification. Thus, in Unit IV.B. of the preamble, the Agency has developed an in-depth discussion of specific concerns, and the manner in which they are addressed. 2. USDA responded favorably to the discussion of rationales for scope Options 1 and 2, but felt that the discussion could be improved by replacing or modifying a reference to Dutch Elm disease in order to more accurately illustrate potential risk from the introduction of a microbial pesticide. EPA Response: EPA has modified the discussion as recommended. 3. USDA stated its belief that the definition of pesticidal property as it appeared in the June 28, 1991 draft, ``any characteristic exhibited by a microorganism that contributes to the ability of the microorganism to prevent, destroy, repel, or mitigate a pest or to act as a plant regulator, defoliant, or desiccant,'' was too broad and seemed ``to go beyond the intent of FIFRA in defining pesticidal properties.'' USDA expressed concern that the definition might expand the definition of pesticide to cover microorganisms that have not in the past been regulated under FIFRA as pesticides. For example, USDA was concerned that the definition ``might be applied to plant-associated microorganisms modified solely for the purpose of improving their ability to perform natural functions associated with plant growth protection.'' EPA Response: EPA agrees with USDA that the term ``pesticidal property'' as used in Options 1 and 2 in this proposed regulation should be consistent with FIFRA and the Agency did not intend to suggest an enlargement of the scope of microorganisms subject to FIFRA. Whether a microorganism is subject to FIFRA authority depends on whether it falls within the statutory definition of a pesticide, which cannot be extended by promulgation within a regulation. To address the USDA's concern of a perception of an enlargement, however, the Agency has modified the definition of ``pesticidal property'' to focus on characteristics contributing to the intentional use of the microorganism to prevent, destroy, repel, or mitigate any pest or intended for use as a plant growth regulator, defoliant, or desiccant. With regard to plant associated microorganisms, such microorganisms would only be subject to FIFRA if they met the statutory definition of pesticide. Once a plant-associated microorganism is determined to be a pesticide, it would only be subject to notification if it met the conditions specified in EPA's final scope. It is not, and has never been, EPA's intention to broaden the definition of pesticide by the terms used in this proposed regulation. EPA believes that the language modification discussed above will clarify the Agency's position. 4. USDA stated that a requirement to maintain records describing the selection and use of containment and inactivation controls is not justified, and is so vague as to not have much regulatory utility. EPA Response: EPA has more fully developed the preamble discussion (See Unit V.A. of this preamble) to clarify the provision on the selection and use of containment and inactivation controls, and the advantages and disadvantages of the provision, and has modified the regulatory text. In terms of the comment that the provision is vague, EPA reiterates its perception that this less prescriptive, performance standard approach is less burdensome than other alternative approaches to defining what constitutes a contained facility, while still meeting the objective of ensuring adequate containment. 5. USDA provided several comments concerning the requirements for a notification in 172.48 of the proposal. USDA suggested that the request to provide ``Means and limit of detection using the most sensitive and specific methods available'' was not appropriate for ``risk screening during notification.'' Additional comments focused on the need for unique genetic markers, use of data from the scientific literature, and the identification of habitat for endangered species. EPA Response: EPA believes that the use of sensitive and specific detection methods is essential, but agrees that there will be instances where use of the ``most sensitive and specific methods available'' may not be warranted. Therefore, this provision has been modified to more clearly reflect the Agency's position. EPA also agrees with USDA's additional comments, and has modified 172.48 accordingly. 6. In 172.50(a), EPA states that the Agency will review each notification within 90 days. USDA noted that this section further states that ``under no circumstances shall the proposed test proceed until the submitter has received notice from EPA of its approval....'' USDA interpreted this latter statement as giving EPA unlimited review time, and suggested that it be deleted. EPA Response: EPA is committed to reviewing Notifications in an expeditious manner. EPA believes that the regulation formalizes this commitment, rather than providing unlimited review time and has therefore not deleted the phrase. VIII. Request for Comment The Agency is requesting comment on this proposed rule only to the extent that it would amend or change the existing regulations. The Agency is not soliciting comments on provisions of the existing regulations that would not be changed by this proposal. Specifically, and notwithstanding the inclusion of some of the existing language from 40 CFR 172.3 in this proposal, the Agency will only entertain comments to the extent that they address the proposed changes in that section. 40 CFR 172.3 is reproduced in its entirety solely for clarity and to facilitate understanding of how the changes and amendments fit within the existing regulatory structure. A. Scope of Coverage for the Notification Scheme Under the 1984 and 1986 Policy Statements, notification to EPA prior to initiation of small-scale testing with any genetically modified or nonindigenous microbial pesticide is required. As described in Units III. and IV. of this preamble, the Agency now believes that a smaller subset of these microbial pesticides should be subject to notification prior to initiation of small-scale testing in the environment. The Agency recognizes there may be multiple approaches for identifying the scope of coverage and has discussed three options in Unit IV. of this preamble. The Agency requests comment on the scientific merit of Options 1 and 3 and the extent to which they focus attention on risk issues that warrant consideration before small-scale testing. Specifically, the Agency requests comment on the regulatory clarity of these options, considered in light of the definition of terms for each option, the variability of the criteria for determining whether a microbial pesticide is covered, the level of analysis necessary to determine whether a microbial pesticide is covered, and any explanatory footnotes included for the option. The Agency is particularly interested in commenters' opinions regarding ambiguity or confusion in the meaning or interpretation of terms or footnotes for determining whether a microbial pesticide is subject to notification. Is the Option 3 scope definition with its footnotes sufficient for the researcher to make a determination on the need for notification, or is additional guidance needed? If additional guidance is needed, what criteria or standards should be established for evaluating the relevant risk concerns? The Agency also requests comment on the following issues. Is the inclusion, within the initial scope of Option 3, of microbial pesticides arising from ``natural breeding'' appropriate? With regard to Option 1, does the somewhat higher risk probability associated with targeted changes resulting from deletions and rearrangements of genetic material directly contributing to the microorganism's ability to act as a pesticide justify a requirement for notification at the small-scale testing stage? The definition of ``pesticidal properties'' in Option 1 addresses a broader set of potential risk endpoints than the definition of ``pesticidal activities'' in Option 3. ``Pesticidal properties'' addresses all mechanisms, including those that are indirect, by which microbial pesticides prevent, repel, destroy, or mitigate a pest, or act as plant regulators, defoliants, or desiccants. ``Pesticidal activities'' address a subset of mechanisms (toxin production, infectivity, pathogenicity, or virulence) through which a microorganism prevents, repels, destroys, or mitigates a pest or acts as a plant regulator, defoliant or desiccant. Specifically excluded from the definition of ``pesticidal activities'' in Option 3 are noncytotoxic modes of action such as those brought about by niche exclusion, substrate competition, or nutrient sequestration. Is the broader range of risk endpoints addressed by Option 1 appropriate, or is the Option 3 focus on toxicity and host-pathogen interactions sufficient? Option 3 has a broader initial range or starting point than Option 1 and 2. However, it is probable that many of the microbial pesticides initially covered will ultimately be eligible for exclusion. Do the benefits associated with this approach outweigh the time and effort expended in evaluating, to determine eligibility for exclusion, the microbial pesticides captured by the broader initial starting point? Are the Option 3 exclusions appropriately focused on survivability, competitiveness, and genetic mobility, or should other characteristics also be taken into consideration? Does the second exclusion of Option 3 provide sufficient guidance to researchers to allow them to make a determination of whether their test is eligible for exclusion? Is there sufficient guidance to allow researchers to determine that there is an increase in pesticidal activity when a microorganism is moved from one environment to another? B. Implementation Procedures Unit IV.B.4. of this preamble discusses four mechanisms of implementation: guidance, documentation, third-party review, and retention of records, and discusses the merits of the mechanisms for each scope option. It also indicates the relative need for, and burden associated with, each component for each option. The Agency requests comment on the relative burden posed by these implementation procedures for each option in light of the benefits derived from each approach. EPA is considering a ``points to consider'' guidance document as a part of Option 3 to help guide researchers in arriving at a determination on whether to notify the Agency about a test. Are there appropriate models or criteria for this guidance? What are the benefits of issuing such guidance; and what burdens (if any) would such guidance impose on the research community? EPA also solicits comment on the need for (and, where needed, the nature of) several implementation mechanisms, including documentation, mandatory third-party review, and record retention. In commenting on these mechanisms, EPA is particularly interested in the likelihood that such tests could cause harm, the burden of carrying out these procedures, and their effect on research in this area. EPA also solicits comments on the merits of relying on the scientific judgment of the researcher (and the associated institution) in assessing the broad range of hazard and exposure characteristics associated with small-scale field tests. Will the researcher be cognizant of the risks of the test? Will good experimental practices avoid any significant risk scenarios? EPA also solicits comment on the existence of other mechanisms or incentives that would be effective in limiting the risks of these tests. Such mechanisms may include the use of enforcement measures and existing State liability law. Or, alternatively, does 172.59 provide adequate enforcement powers to address tests that pose unreasonable adverse effects? Are there mechanisms other than the four implementation procedures discussed in this preamble that could assure the Agency that an appropriate risk/benefit balance can be achieved for each test and the FIFRA standard of ``no unreasonable adverse effects'' can be attained? EPA is specifically requesting comment on one procedure for implementing Option 3--third-party review of determinations of whether a microbial pesticide is within the scope. The Agency is proposing that the third party could be local peer review groups such as IBCs, or some other responsible group or individual(s) in the affected organization. The Agency also requests comments on whether this third-party review should be voluntary or mandatory. In the February 15, 1989 Federal Register notice (54 FR 7026, February 15, 1989), EPA specifically asked for comment on the merit and feasibility of establishing specific, formal, EPA-approved type of local peer review groups, Environmental Biosafety Committees (EBCs). While there was some support for this concept in principle, a large number of issues were raised in the comments. These included: Liability of the individual members and the supporting institution/company; consistency and equality of reviews; allocation of costs and burdens of establishing and maintaining committees; availability of peer review groups to those who could not afford to establish them; delegation of Agency authority; public access to proceedings and records; conflict of interest; protection of CBI; timeliness of committee reviews; amount of discretion allowed peer review groups in decision-making; availability of experts to staff them; avoidance of duplicative reviews; need for procedures to govern nomination, selection and removal of members and consultants; and, need for a process that would allow an interested party to petition EPA to review the committee's decisions. The third-party review procedure EPA would utilize to implement Option 3 differs in several important ways from the 1989 approach to EBCs, and thus avoids some of the concerns raised by the public with regard to that proposal. The primary function of the third-party review associated with Option 3 would be to ensure that a researcher's determination of whether a microbial pesticide test is subject to the notification process is appropriate. EPA is not proposing to place specific membership requirements, certification procedures, conflict-of-interest provisions, approval procedures or provisions for public participation on the third party that would evaluate the status of tests involving microbial pesticides potentially subject under Option 3. Some issues the public raised concerning EBCs can be resolved, others may be obviated, and others remain outstanding by the third-party review procedures of Option 3. However, EPA believes that some type of third-party review is essential to integrating the scope set out by Option 3 into the FIFRA regulatory structure. In this context, the advantages of third-party review outweigh the disadvantages. EPA requests comment on the utility of third-party review, including the possible use of biosafety committees to implement Option 3. Finally, EPA requests comment on whether researchers, if given the choice, would prefer to have the biosafety committee or EPA perform the third-party review to ensure the determination of notification status is appropriate. C. Nonindigenous Microbial Pesticides In Unit IV.B.5. of this preamble, EPA stated its rationale for excluding from the notification requirement naturally occurring nonindigenous microbial pesticides. The Agency requests comment on whether a category can be identified at this time consisting of nonindigenous microbial pesticides that pose a potential for significant risk to human health or the environment when used in testing at small-scale that are not otherwise reviewed by another Federal agency. D. Testing in Contained Facilities The Agency does not propose to require notification for testing conducted in facilities for which there are adequate containment and inactivation controls. As discussed in Unit V.A. of this preamble, selection and use of specific containment and inactivation controls would be at the discretion of the individual or institution conducting the test. EPA requests comment on the scientific merit, regulatory utility and burden of this approach, particularly with regard to whether the regulatory text is sufficiently clear to allow researchers to comply. In addition, EPA is requesting comment on whether records describing the selection and use of the containment and inactivation controls should be required, and how this type of documentation might best be accomplished. For example, the Agency seeks comment on what level of documentation (e.g., protocols and operational records) would be appropriate to support a claim that adequate containment controls are in place during testing and whether there is a need for additional Agency guidance on containment. EPA also requests comment on how these provisions might be handled for Option 3, which has a broader initial scope of coverage. E. Substantiation of Claims for Confidential Information The Agency requests comment on the proposed requirement (172.46(d)) that any claim of confidentiality must be substantiated at the time the claim is made. Specifically, the Agency 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 SAP meetings) and industry's desire to receive timely responses on notifications. 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 environmental releases and their potential environmental or human health effects. EPA believes that, given the Agency's procedural requirements for CBI determinations, without up front substantiation, a 90 - day response time would be difficult or impossible when it becomes necessary to resolve the issue of CBI before a decision can be made. F. Voluntary Submissions Interested parties representing industry and public interest groups have suggested that, in addition to the notification requirement, the Agency offer industry the opportunity to obtain review from a Federal agency on a voluntary basis, (e.g., a ``courtesy letter'') before the initial introduction of any microorganism that the company believes could benefit by such a review, regardless of the scope of coverage for notification in the final rule. For example, certain microbial pesticides not covered by the scope, would be evaluated to confirm that they are indeed excluded from the scope of coverage, and that no further notification is necessary until large-scale testing. This approach, although more burdensome for the Agency, would provide additional assurance to non-Federal agencies and the public that the responsible Federal authorities are informed of the testing, and would assure that the researcher and the regulatory authority are in agreement on whether the microbial pesticide is excluded from the scope. The Agency requests comment on this suggestion. G. Potential Exemptions from the Scope of Coverage EPA requests comment on the scientific merit of adding one or more of the following categorical exemptions to Option 1, by adding these categories to  172.45 (d)(1): (1) Microorganisms modified solely by rearrangement (i.e., translocation or inversion) or deletion of nucleotide sequences, within a single genome, including its extrachromosomal elements; or, (2) microorganisms that do not have a host dependent stage and that have been modified solely by rearrangement (i.e., translocation or inversion) or deletion of nucleotide sequences, within a single genome, including its extrachromosomal elements. (``Genome'' would be defined as the sum total of chromosomal and extrachromosomal genetic material of an isolate and any descendant derived under axenic culture conditions from that isolate.) Option 1, as set forth in 172.45, already excludes all microbial pesticides modified by deletions or rearrangements that do not affect pesticidal properties. It also excludes deletions and rearrangements that may affect pesticidal properties but do not involve the introduction of modified genetic material. Similarly, Options 2 and 3 could be further modified by the addition of exclusion categories. IX. Regulatory Requirements A. Executive Order 12291 Under Executive Order 12291, EPA must judge whether a rule is ``major'' and, therefore, subject to the requirement of a Regulatory Impact Analysis. The Agency has evaluated this proposal against the requirements of E.O. 12291 and concludes that the proposal is not a major rule. This proposal has been submitted to the Office of Management and Budget (OMB) for review as required by section 3 of E.O. 12291. B. Regulatory Flexibility Act Under the Regulatory Flexibility Act (5 U.S.C. 605 (b)), EPA certifies that this proposed rule will not have a significant economic impact on a substantial number of small businesses. This conclusion is based on the fact that this proposal is only the codification, with modification, of relevant operative provisions of the June 26, 1986 Policy Statement. As such, this proposal will not create any additional impacts on affected small businesses or other small entities beyond those currently in effect. In fact, this proposal would reduce the number and scope of microbial pesticides requiring EPA oversight from those covered under the current policy. C. Paperwork Reduction Act The information collection requirements in this proposed rule were submitted to OMB for approval under the Paperwork Reduction Act, 44 U.S.C. 3501 et seq. Public reporting burden for this collection of information is estimated to vary from 45 to 181 hours per response when no EUP is required and to vary from 2,887 to 4,475 hours per response when an EUP is required. The average number of burden hours are estimated to be 113 and 3,681 hours per response, respectively. This includes 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, PM - 223, U.S. 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 40 CFR Part 172 Environmental protection, Intergovernmental relations, Labeling, Pesticides and pests, Recordkeeping and reporting requirements, Research. Dated: January 14, 1993. William K. Reilly, Administrator. Therefore, it is proposed that 40 CFR part 172 be amended as follows: Part 172--[AMENDED] 1. The authority citation for part 172 would be revised to read as follows: Authority: 7 U.S.C. 136a, 136c, 136v, and 136w. 2. By revising 172.3 to read as follows: 172.3 Scope of requirement. (a) An experimental use permit is generally required for testing of any unregistered pesticide or any registered pesticide for a use not previously approved by EPA in the pesticide's registration. However, as described below in paragraph (b) of this section, certain of such test using a pesticidal substance or mixture of substances are presumed not to involve unreasonable risks and, therefore, do not require an experimental use permit. (b) Except as provided in subpart C of this part or as specifically determined by EPA, it may be presumed that experimental use permits are not required when: (1) The experimental use of the substance or mixture of substances is limited to: (i) Laboratory or greenhouse tests, (ii) Limited replicated field trials as described in paragraph (c) of this section to confirm such tests, or (iii) Other tests as described in paragraph (c) of this section whose purpose is only to assess the pesticide's potential efficacy, toxicity, or other properties; and (2) The producer, applicator, or any other person conducting the test does not expect to receive any benefit in pest control from the pesticide's use. (c) For purposes of paragraphs (b)(1)(ii) and (b)(1)(iii) of this section, the following types of experimental tests are presumed not to need an experimental use permit: (1) A small-scale test involving use of a particular pesticidal substance or mixture of substances that is conducted on a cumulative total of no more than 10 acres of land, provided that: (i) When more than one intended target pest occurs at the same time in the same locality, the 10 acre limitation shall encompass all of the intended target pests. (ii) When more than one target pest is intended, and they do not occur at the same time or in the same locality (or application of the pesticide would not be at the same time), up to 10 acres may be treated for each target pest. (iii) Any food or feed crops involved in, or affected by, such tests (including, but not limited to, crops subsequently grown on such land which may reasonably be expected to contain residues of the tested pesticidal substances) shall be destroyed or consumed only by experimental animals unless a tolerance or an exemption from a tolerance has been established under the Federal Food, Drug, and Cosmetic Act for residues of the pesticide in or on the crop. (2) A small-scale test involving the use of a particular pesticidal substance or mixture of substances that is conducted on a cumulative total of no more than 1 surface acre of water, provided that: (i) When more than one intended target pest occurs at the same time in the same locality, the 1 acre limitation shall encompass all of the intended target pests. (ii) When more than one target pest is intended, and they do not occur at the same time or in the same locality (or application of the pesticide would not be at the same time), up to 1 acre may be treated for each target pest. (iii) Waters which are involved in or affected by such tests are not used for irrigation purposes, drinking water supplies, or body contact recreational activities. (iv) Testing shall not be conducted in any waters which contain or affect fish, shellfish, plants, or animals taken for recreational or commercial purposes and used for food or feed, unless a tolerance or exemption from a tolerance has been established under the Federal Food, Drug, and Cosmetic Act for residues of the test substance in or on the crop. (3) Animal treatment tests involving the use of a particular pesticidal substance or mixture of substances that are conducted only on experimental animals which will not be used for food or feed, unless a tolerance or an exemption from a tolerance has been established for animal products and byproducts. (d) The examples in paragraphs (c)(1) and (c)(2) of this section are all-inclusive and do not preclude testing in larger areas or larger numbers of units if the intended use meets the criteria of paragraph (b) of this section. However, tests which do not come within the examples in paragraphs (c)(1) and (c)(2) of this section, absent a specific determination by EPA to the contrary, require an experimental use permit. Subdivision I of the Pesticide Assessment Guidelines specifies, by way of further example, testing which requires an experimental use permit. Persons intending to conduct tests who are uncertain whether the testing may be conducted without a permit may submit a request for determination to the Registration Division, Office of Pesticide Programs. Such a request shall include the information listed in 172.4(b)(1)(ii) and (b)(1)(iii), and in the case of an unregistered product, the information in  172.4(b)(3)(i). (e) Notwithstanding paragraphs (b) through (d) of this section, EPA may, on a case-by-case basis, require that certain testing of a particular pesticide or class of pesticides be carried out under an experimental use permit, if it is determined that such EPA oversight is warranted. (f) No experimental use permit is required for a substance or mixture of substances being put through tests for the sole purpose of gathering data required for approval of such substances or mixture under the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 301 et seq.) as: (1) A ``new drug'' (21 U.S.C. sec. 321(p) and sec. 355). (2) A ``new animal drug'' (21 U.S.C. sec. 321(w) and sec. 360(b)), or (3) An ``animal feed'' (21 U.S.C. sec. 321 (x)) containing a ``new animal drug'' (21 U.S.C. sec. 360(b)). (g) Paragraph (f) of this section shall not apply when a purpose of such test is to accumulate information necessary to register a pesticide under section 3 of the Act. 3. By establishing a new subpart C to read as follows: Subpart C--Notification for Certain Genetically Modified Microbial Pesticides Sec. 172.43 Definitions. 172.45 Requirement for a Notification. 172.46 Submission of a Notification. 172.48 Data requirements for a Notification. 172.50 Response to a Notification. 172.52 Notification exemption process. 172.57 Submission of information regarding potential unreasonable adverse effects. 172.59 Enforcement. Subpart C--Notification for Certain Genetically Modified Microbial Pesticides 172.43 Definitions. Terms used in this subpart shall, with the exception of those defined below, have the meaning set forth in the Act and in 172.1. Containment and inactivation controls means any combination of mechanical, procedural, or biological controls designed and operated to restrict environmental release of viable microorganisms from a facility. Deliberately modified means the directed addition, rearrangement, or removal of a nucleotide sequence(s) to or from genetic material. Introduction of genetic material means the movement of a nucleotide sequence(s) into a microorganism, regardless of the technique used. Microbial pesticide means any pesticide whose active ingredient is a bacterium, fungus, alga, virus, or protozoan intended for preventing, destroying, repelling, or mitigating any pest, or intended for use as a plant regulator, defoliant, or desiccant. Pesticidal property means a characteristic exhibited by a microorganism that contributes to the intentional use of the microorganism to prevent, destroy, repel, or mitigate a pest or to act as a plant regulator, defoliant, or desiccant. Small-scale test means the experimental use of a microbial pesticide in a facility such as a laboratory or greenhouse, or use in limited replicated field trials or other tests as described in 172.3(c). Test or testing means any use of a microbial pesticide consistent with section 5 of the Act, including limited replicated field trials and associated activities. 172.45 Requirement for a Notification. (a) Who must submit a Notification. Notwithstanding 172.3, any person who plans to conduct small-scale testing of a type of microbial pesticide identified in paragraph (c) of this section must submit a Notification to EPA and obtain prior approval for either of the following tests: (1) Small-scale tests that involve an intentional environmental introduction of that microbial pesticide. (2) Small-scale tests performed in a facility without adequate containment and inactivation controls as provided in paragraph (e) of this section. (b) Alternative to Notification. In lieu of a Notification, any person required to submit a Notification under paragraph (a) of this section may submit an application for an experimental use permit (EUP) to EPA for approval. (c) Small-scale testing that requires a Notification. As provided in paragraph (a) of this section, and notwithstanding any other approval, EPA review and approval are required prior to the initiation of any small-scale test involving microbial pesticides whose pesticidal properties have been imparted or enhanced by the introduction of genetic material that has been deliberately modified. (d) Small-scale testing that does not require a Notification. (1) Testing conducted with microbial pesticides exempt pursuant to 172.52 does not require a Notification. The following microbial pesticides (or classes of pesticides) identified in paragraph (c) of this section are exempt from the notification requirement in paragraph (a) of this section: (i) [Reserved] (ii) [Reserved] (2) Testing conducted in a facility with adequate containment and inactivation controls, as provided in paragraph (e) of this section does not require a Notification. (e) Selection and use of containment and inactivation controls. (1) Selection and use of containment and inactivation controls for a particular microorganism shall take into account the following: (i) Factors relevant to the microorganism's ability to survive in the environment. (ii) Potential routes of release in air, solids, and liquids; in or on waste materials and equipment; in or on people (including maintenance and custodial personnel); and in or on other organisms such as insects and rodents. (iii) Procedures for transfer of materials between facilities. (iv) Plans for routine or emergency clean-up and test termination. (2) The selection of containment and inactivation controls shall be approved by an authorized official of the organization that is conducting the test prior to commencement of the test. (3) [Reserved] (4) Subsequent to any EPA review of the containment/ inactivation controls selected under paragraph (e)(1) of this section, changes to the controls necessary to prevent unreasonable adverse effects must be made upon EPA request. Failure to comply with EPA's request shall result in automatic revocation of the exemption from the requirement to submit a Notification. 172.46 Submission of Notification. (a) When to submit a Notification. A Notification shall be submitted for approval at least 90 days prior to the initiation of the proposed test. (b) Where to submit a Notification. A Notification shall be submitted to the Registration Division (H7505C), Office of Pesticide Programs, Environmental Protection Agency, 401 M St., SW., Washington, DC 20460, and clearly marked ``ATTN: Biotechnology Notification Review.'' (c) How to format a Notification. A Notification submitted under this section must comply with the following procedures, but is not required to comply with the format and other provisions governing submission of data in 158.32 and 158.33 of this chapter. However, because data submitted with the Notification may subsequently be used to support other regulatory actions (e.g., used in EUP or registration applications), it is recommended that such data comply with EPA requirements. (1) Each Notification must be accompanied by a transmittal document that clearly identifies the EPA action supported as a Biotechnology Notification Review. (2) Five copies of each Notification must be submitted to EPA. (3) Any claims of confidentiality for information submitted in the Notification must be made as described in paragraph (d) of this section. (d) How to make confidential business information (CBI) claims in a Notification. 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 Notification. (See part 2, subpart B of this chapter.) To assert such a claim, the submitter must comply with the following procedures: (1) 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 the Act, with no further notice to the submitter. (2) Of the five copies of the Notification required by paragraph (c) of this section, four copies must be complete with the information that is claimed confidential clearly marked in the manner described in 2.203(b) of this chapter. All information claimed as confidential must be deleted from the fifth copy, but it must be otherwise complete. The first page of the fifth copy must be marked ``Contains no information claimed as confidential.'' EPA may include the fifth copy in a public file. EPA will consider incomplete a Notification containing information claimed as CBI that is not submitted in accordance with this paragraph and will suspend the review period on the Notification until such procedures are followed. (3) 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 2.204(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 2.205(c) of this chapter. EPA will consider incomplete all Notifications containing information claimed as CBI that are not accompanied by substantiation, and will suspend the review period on such Notifications until the required substantiation is provided. (4) EPA will disclose information that is subject to a claim of confidentiality asserted under this section only to the extent and by means of the procedures set forth in section 10 of the Act, in this subpart, and in part 2 of this chapter. 172.48 Data requirements for a Notification. This section identifies the data and information to be included in each Notification. When specific information is not submitted, an explanation of why it is not practical or necessary to provide the information is to be provided. (a) The identity of the microorganism which constitutes the microbial pesticide including: (1) Summary of data supporting the taxonomic designation and its interpretation. (2) Means and limit of detection using sensitive and specific methods (e.g., note the use of any markers that are used to distinguish the introduced population from native microorganisms). Introduction into the microorganism of a unique genetic marker is encouraged. (b) Description of the natural habitat of the parental strain of the microorganism including information on: (1) Physical and chemical features important to growth and survival of the microorganism. (2) Biological features that would have an impact on the microorganism (e.g., presence of phages that infect the microorganism). (3) Competitors. (c) Information on the host range of the microorganism, if any, with an assessment of infectivity and pathogenicity to nontarget organisms. (d) Information on survival and ability of the microorganism to increase in numbers (biomass) in the environment (e.g., in the environment into which the microbial pesticide will be introduced, and in substantially different environments that may be in the immediate vicinity). These data may be derived from the scientific literature or from tests conducted in a laboratory or other containment facility. (e) The identity of possible transmission vectors (e.g., insects). (f) Data on relative environmental competitiveness compared to the parental strain of the microorganism. (g) Description of the methods used to genetically modify the microorganism. (h) The identity and location of the gene segments that have been rearranged or inserted/deleted (host source, nature, and, for example, base sequence data, or restriction enzyme map of the gene(s)). (i) Information on the control region of the gene(s), and a description of the new trait(s) or characteristic(s) that are expressed. (j) Data on potential for genetic transfer and exchange with other organisms and on genetic stability of any inserted sequence. (k) A description of the proposed testing program including: (1) The purpose or objectives of the proposed testing. (2) Designation of the pest organism(s) involved (common and scientific names). (3) The State(s) in which the proposed program will be conducted. (4) The exact location of the test site(s) (including proximity to residences and human activities, surface water, etc.). (5) The crops, fauna, flora, geographical description of sites, modes, dosage rates, frequency, and situation of application on or in which the pesticide is to be used. (6) The total amount of pesticide product proposed for use in the testing. (7) The method of application. (8) A comparison of the natural habitat of the microorganism with the proposed test site. (9) The number of acres, structural sites, or animals/plants by State, to be treated or included in the area of experimental use. (10) Procedures to be used to protect the test area from intrusion by unauthorized individuals. (11) The proposed date(s) or period(s) during which the testing program is to be conducted, and the manner in which supervision of the program will be accomplished. (12) Description of procedures for monitoring the microorganism within and adjacent to the test site during the test. (13) The method of sanitation or disposal of plants, animals, soils, farm tools, machinery etc., that will be exposed to the microbial pesticide during or after the test. (14) Means of evaluating potential adverse effects and methods of controlling the microorganism if detected beyond the test area. (l) A statement of composition for the formulation to be tested, giving: (1) The name and percentage by weight (or other suitable units) of each ingredient, active and inert. (2) Production methods. (3) Extraneous microorganisms present as contaminants. (4) Amount and potency of any toxin present. (5) Where applicable, the number of viable microorganisms per unit weight or volume of the product or other appropriate system for designating the quantity of active ingredient. (m) Any additional factual information regarding the potential for unreasonable adverse effects on the environment. 172.50 Response to a Notification. (a) EPA will review and evaluate each Notification as expeditiously as possible and will make a determination no later than 90 days after receipt of the complete Notification; however, under no circumstances shall the proposed test proceed until the submitter has received notice from EPA of its approval of such test. (b) For each Notification, EPA may make the following determinations: (1) Require additional information from the submitter to assess the proposed test adequately. (2) Approve the proposed test. (3) Approve the proposed test provided that the submitter makes certain modifications to the test proposal. (4) Require an experimental use permit for the test. (5) Disapprove the proposed test because of the potential for unreasonable adverse effects. Such disapproval by EPA shall be considered the equivalent of denial of an experimental use permit and the remedies for such denial provided by 172.10 are available to the submitter. (c) If the proposed test is approved by EPA, then the submitter shall perform the test in the same manner described in the Notification, subject to any requirements imposed under paragraph (b)(3) of this section. 172.52 Notification exemption process. (a) Initiation of the exemption process. Pesticides may be added to the list of exemptions in 172.45(d) by rule at EPA's initiative or in response to a petition submitted in accordance with paragraph (f) of this section. (b) Petitions for exemption from the requirement for a Notification--(1) Who may submit a petition. Any person may submit a petition requesting an exemption from the notification requirements of this subpart for a specific microbial pesticide or class of microbial pesticides. (2) Where to submit a petition. All petitions shall be submitted to the following location: Registration Division (H7507C), Office of Pesticide Programs, Environmental Protection Agency, 401 M St., SW., Washington, DC 20460. (3) Content of petition. Each petition shall contain the following: (i) Name and address of petitioner and name, address, and telephone number of person who may be contacted for further information. (ii) Description of the exemption requested, including the specific microorganisms or class of microorganisms to be tested. (iii) Basis for the petitioner's contention that the specific microbial pesticide or class of microbial pesticides meets the criteria of 172.3 for small-scale tests of pesticides that do not require an experimental use permit. (iv) Discussion of the extent to which the microbial pesticide or class of microbial pesticides covered by the petition differ from microbial pesticides that are already registered or subject to an experimental use permit under the Act. (4) Administrative action on a petition. EPA will review and evaluate petitions as expeditiously as possible and may request further information from the petitioner to assess the proposed exemption adequately. No later than 180 days after the submission of a petition, or 90 days after the last submission of additional information by the petitioner, whichever is later, EPA will take one of the following actions with respect to the petition: (i) Grant the petition and publish a notice of proposed rulemaking in the Federal Register for a 30 - day comment period proposing the exemption requested by the petitioner. (ii) Grant the petition and publish a notice of proposed rulemaking in the Federal Register for a 30 - day comment period proposing an exemption under such terms and conditions as EPA deems appropriate. (iii) Deny the petition and provide the petitioner with a written explanation of EPA's decision. (5) Confidential business information (CBI) claims. To assert a claim of confidentiality, the petitioner must comply with the applicable procedures in 172.46(d). (6) Supplements, amendments, and withdrawals. The petitioner may supplement, amend, or withdraw his or her petition in writing without EPA approval at any time prior to the granting or denial of the petition under paragraph (b)(4) of this section. The withdrawal of a petition shall be without prejudice to the resubmission of the petition at a later date. 172.57 Submission of information regarding potential unreasonable adverse effects. Any person using a microbial pesticide in small-scale testing covered by this subpart who obtains information regarding potential unreasonable adverse effects on 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. The requirement to submit information applies both to those microbial pesticides subject to the notification requirements under 172.45(c) and those that are exempt under 172.45(d). 172.59 Enforcement. (a) Imminent threat of substantial harm to health or the environment. The use of a microbial pesticide in small-scale testing covered by this subpart (whether subject to the notification requirements of 172.45(c) or exempt under 172.45(d)) in a manner that creates an imminent threat of substantial harm to health or the environment is prohibited, and is considered a violation of section 12(a)(2)(S) of the Act. (b) EPA response to violations. Under sections 14 and 16(c) of the Act, EPA may at any time take appropriate action against violators to prevent or otherwise restrain use of a microbial pesticide in small-scale testing if it is determined that: (1) Such use would create an imminent threat of substantial harm to health or the environment that is prohibited under paragraph (a) of this section; or (2) The terms or conditions on which approval of the testing was granted under 172.43 through 172.55 are violated. [FR Doc. 93 - 1596 Filed 1 - 19 - 93; 9:57 am] BILLING CODE 6560 - 50 - F