Wednesday, October 8, 2008

Part III

Environmental Protection Agency 40 CFR Parts 158 and 161 Data Requirements for Antimicrobial Pesticides; Proposed Rule

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00001 Fmt 4717 Sfmt 4717 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59382 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

ENVIRONMENTAL PROTECTION consider to be CBI or otherwise I. General Information protected through regulations.gov or e- AGENCY A. Does this Action Apply to Me? mail. The regulations.gov website is an 40 CFR Parts 158 and 161 ‘‘anonymous access’’ system, which You may be affected by this action if RIN 2070–AD30 means EPA will not know your identity you are a producer of pesticide products or contact information unless you (NAICS 32532), antifoulants (NAICS Data Requirements for Antimicrobial provide it in the body of your comment. 32551), antimicrobial pesticides (NAICS Pesticides If you send an e-mail comment directly 32561) or wood preservatives (NAICS to EPA without going through 32519), importers of such products, or AGENCY: Environmental Protection regulations.gov, your e-mail address any person or company who seeks to Agency (EPA). will be automatically captured and register an antimicrobial, antifoulant ACTION: Proposed rule. included as part of the comment that is coating, ballast water treatment, or placed in the docket and made available wood preservative pesticide or to obtain SUMMARY: EPA proposes to revise and on the Internet. If you submit an a tolerance for such a pesticide. This update the existing data requirements electronic comment, EPA recommends listing is not intended to be exhaustive, for antimicrobial pesticides. The that you include your name and other but rather provides a guide for readers proposed revisions are needed to reflect contact information in the body of your regarding entities likely to be affected by current scientific knowledge and comment and with any disk or CD-ROM this action. Other types of entities not current Agency regulatory practices, and you submit. If EPA cannot read your listed above could also be affected. The to improve protection of the general comment due to technical difficulties North American Industrial population as well as sensitive and cannot contact you for clarification, Classification System (NAICS) codes subpopulations. The proposed EPA may not be able to consider your have been provided to assist you and requirements are intended to further comment. Electronic files should avoid others in determining whether this enhance the Agency’s ability to make the use of special characters, any form action might apply to certain entities. If regulatory decisions about the human of encryption, and be free of any defects you have any questions regarding the health and environmental fate and or viruses. applicability of this action to a effects of antimicrobial pesticide particular entity, please contact Norm products. Docket: All documents in the docket are listed in the docket index available Cook, Chief of the Risk Assessment and DATES: Comments must be received on in regulations.gov. To access the Science Support Branch in the or before January 6, 2009. electronic docket, go to http:// Antimicrobials Division of the Office of ADDRESSES: Submit your comments, www.regulations.gov, select ‘‘Advanced Pesticide Programs at 703–308–8253 or identified by docket identification (ID) Search,’’ then ‘‘Docket Search.’’ Insert via email, [email protected]. number EPA–HQ–OPP–2008–0110, by the docket ID number where indicated B. What Should I Consider as I Prepare one of the following methods: and select the ‘‘Submit’’ button. Follow My Comments for EPA? • Federal eRulemaking Portal: http:// the instructions on the regulations.gov www.regulations.gov. Follow the on-line website to view the docket index or 1. Docket. EPA has established a instructions for submitting comments. access available documents. Although docket for this action under docket • Mail: Office of Pesticide Programs listed in the index, some information is identification (ID) number EPA–HQ– (OPP) Regulatory Public Docket (7502P), not publicly available, e.g., CBI or other OPP–2008–0110. Publicly available Environmental Protection Agency, 1200 information whose disclosure is docket materials are available either in Pennsylvania Ave., NW., Washington, restricted by statute. Certain other the electronic docket at http:// DC 20460–0001. material, such as copyrighted material, www.regulations.gov, or, if only • Delivery: OPP Regulatory Public is not placed on the Internet and will be available in hard copy, at the Office of Docket (7502P), Environmental publicly available only in hard copy Pesticide Programs (OPP) Regulatory Protection Agency, Rm. S–4400, One form. Publicly available docket Public Docket in Rm. S–4400, One Potomac Yard (South Bldg.), 2777 S. materials are available either in the Potomac Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, VA 22202. electronic docket at http:// Crystal Dr., Arlington, VA 22202. The Deliveries are only accepted during the www.regulations.gov, or, if only hours of operation of this Docket Docket’s normal hours of operation available in hard copy, at the OPP Facility are from 8:30 a.m. to 4 p.m., (8:30 a.m. to 4 p.m., Monday through Regulatory Public Docket in Rm. S– Monday through Friday, excluding legal Friday, excluding legal holidays). 4400, One Potomac Yard (South Bldg.), holidays. The Docket Facility telephone Special arrangements should be made 2777 S. Crystal Dr., Arlington, VA number is (703) 305–5805. for deliveries of boxed information. The 22202. The hours of operation of this 2. Tips for preparing your comments. Docket Facility telephone number is Docket Facility are from 8:30 a.m. to 4 When submitting comments, remember (703) 305–5805. p.m., Monday through Friday, excluding to: Instructions: Direct your comments to legal holidays. The Docket Facility i. Identify the document by docket ID docket ID number EPA–HQ–OPP–2008– telephone number is (703) 305–5805. number and other identifying 0110. EPA’s policy is that all comments FOR FURTHER INFORMATION CONTACT: information (subject heading, Federal received will be included in the docket Kathryn Boyle, Field and External Register date and page number). without change and may be made Affairs Division, Office of Pesticide available on-line at http:// ii. Follow directions. The Agency may Programs, Environmental Protection www.regulations.gov, including any ask you to respond to specific questions Agency, 1200 Pennsylvania Ave., NW., personal information provided, unless or organize comments by referencing a Washington, DC 20460–0001; mail code the comment includes information Code of Federal Regulations (CFR) part 7506P; telephone number: 703–305– claimed to be Confidential Business or section number. 6304; fax number: 703–305–5884; e-mail Information (CBI) or other information iii. Explain why you agree or disagree; address: [email protected]. whose disclosure is restricted by statute. suggest alternatives and substitute Do not submit information that you SUPPLEMENTARY INFORMATION: language for your requested changes.

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00002 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59383

iv. Describe any assumptions and docket for this proposed rule (Ref. 43). requirements for antimicrobial provide any technical information and/ The white paper discusses the current pesticides until a new rule tailored or data that you used. level of information and usage of specifically to antimicrobial pesticides v. If you estimate potential costs or structure-activity-relationship (SAR) could be promulgated. Part 161 is burdens, explain how you arrived at assessments and Quantitative SAR intended to be transitional. Once your estimate in sufficient detail to (QSAR) modeling to fulfill data subpart W of part 158 is promulgated, allow for it to be reproduced. requirements in the Pesticide Program. there will be no need for part 161. vi. Provide specific examples to The Agency specifically seeks comment Accordingly, EPA proposes to revoke illustrate your concerns and suggest on this support document. part 161 upon the effective date of a alternatives. Since many antimicrobial pesticides final rule arising from today’s proposal. vii. Explain your views as clearly as are typically rinsed down the drain, B. Reasons for Today’s Action possible, avoiding the use of profanity EPA has considered the potential or personal threats. impacts of pesticides that are discharged Since the promulgation of part 158 in viii. Make sure to submit your into wastewater treatment plants 1984, the Agency has recognized that comments by the comment period (WWTPs). This proposed rule addresses the tables and test notes promulgated in deadline identified. the issue of down-the-drain 1984 failed to adequately address the antimicrobials by proposing four new unique applications, use patterns, and II. Background data requirements for use in a screening- other factors germane to antimicrobial A. What Action is the Agency Taking? level assessment on the fate of pesticides. Part 158 specifies the types antimicrobials that reach a WWTP. To of data and information generally The Environmental Protection Agency assess the impacts of this screening required for making sound regulatory (EPA or the Agency) is proposing to assessment and utility of the new data judgments under the Federal establish a separate listing of the data requirements for decision-making, EPA Insecticide, Fungicide, and Rodenticide requirements for antimicrobial prepared four case studies (Ref. 42). The Act (FIFRA). The types of actions for pesticides in Title 40 of the Code of case studies, copies of which are which these data are needed include Federal Regulations (CFR) in subpart W contained in the docket for this experimental use, registration, amended of part 158. This proposal sets out use proposed rule, are discussed in more registration, reregistration, or patterns that are designed to make it detail in Unit XII.D. The Agency registration review (collectively referred easier to determine which requirements specifically seeks comment on the to in this proposal as ‘‘registration’’). apply to antimicrobial products. In proposed approach for evaluating the The information required under FIFRA addition to retaining most current data potential impact of antimicrobial for registration of food-use pesticides is requirements for antimicrobials, this pesticide chemicals on WWTPs and also information the Agency needs in proposal incorporates nine new data nontarget organisms in receiving water order to grant tolerances or exemptions requirements and revises other existing bodies, and on the case studies, from the requirement of tolerances data requirements. This rule, once final, including the assumptions used in those under section 408 of the Federal Food, is intended to further enhance the studies, that were used to develop the Drug, and Cosmetic Act (FFDCA). Agency’s ability to make regulatory proposed approach. EPA will consider Required data are intended to provide decisions about the human health, and comments specific to the case studies information about the potential adverse environmental fate and effects of along with comments on the proposed effects of uses of pesticides, and to antimicrobial pesticide products. approach, as the Agency evaluates the define what is generally expected from The Agency has previously issued use of the proposed approach for down- applicants for registration in support of updated data requirements for the-drain antimicrobials in the final rule their products. However, it must be conventional pesticides, and for antimicrobial data requirements. emphasized that each applicant has the biochemical and microbial pesticides in On October 26, 2007, EPA continuing obligation under FIFRA to part 158. This proposal is part of a larger promulgated final rules establishing demonstrate that an individual product effort to update and improve all of the data requirements for conventional meets the standard for registration data requirements for pesticide pesticides (72 FR 60934), and under section 3 of FIFRA or section 408 regulatory purposes. Data requirements biochemical pesticides and microbial of FFDCA. Accordingly, as indicated in for antimicrobial pesticides, currently pesticides (72 FR 60988). These final current § 158.75 and § 161.75, contained in part 161, are proposed to rules were effective on December 24, additional data may be needed to reflect be revised and included in part 158 2007, and are therefore the current part the characteristics and use of specific upon promulgation. 158. As part of those actions, on October pesticide products under review. Generally, antimicrobials are 24, 2007, (72 FR 60251) EPA preserved Since the data requirements now set considered to be those chemicals that the original part 158 data requirements out in part 161 (formerly part 158) were disinfect and sanitize. However, within to provide continued regulatory first published in 1984, every this proposal EPA is using the term coverage for antimicrobial pesticides disciplinary area and requirement has antimicrobials to collectively refer to until the Agency could promulgate a been reconsidered and many have been antimicrobial pesticides, antifoulant final regulation. To accomplish this, revised in practice. These changes have coatings and paints, and wood EPA transferred intact the original 1984 been needed because the state of the preservatives. data requirements of part 158 into a new science underlying the data As discussed in Unit XVIII.A., EPA part 161, entitled ‘‘Data Requirements requirements has advanced, and has prepared a white paper entitled for Antimicrobial Pesticides.’’ Part 161, because the Agency has learned in ‘‘Use of Structure-Activity Relationship which applies only to antimicrobial specific registration actions that (SAR) Information and Quantitative pesticides, contains the current data additional or different data are SAR (QSAR) Modeling For Fulfilling requirements for antimicrobial pesticide necessary to make sound regulatory Data Requirements for Antimicrobial chemicals. decisions. These case-by-case decisions Pesticide Chemicals and Informing As explained in the preamble to the have been made in accordance with EPA’s Risk Management Process,’’ a conventional pesticide final rule, EPA § 158.75, which allows the Agency to copy of which is contained in the intended to preserve the existing data impose additional data requirements

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00003 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59384 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

beyond those specified in part 158 and lenient, but also benefit the regulated submitted to the extent it helps inform now part 161. industry by reducing the uncertainty in their decisions about whether or how to Use patterns specific to antimicrobial Agency risk assessments. Thus, today’s use particular pesticides to avoid pesticides are not specified in part 161, proposal will reduce, but not eliminate, potential exposure. as they were not set out separately when uncertainty related to the risks posed by D. What is the Agency’s Authority for originally promulgated in 1984. As a antimicrobial pesticides. result, applicants have needed to 2. Clarity and transparency to Taking this Action? interpret the data requirements often via regulated community means savings. This action is issued under the extensive consultation with and The enhanced clarity and transparency authority of sections 3, 4, 5, 10, 12, and interpretation from the Agency to of the information presented in part 158, 25 of FIFRA as amended and section determine the antimicrobial data subpart W should enhance the ability of 408 of FFDCA. The data required for a requirements for a particular product. industry to efficiently manage their registration, reregistration, experimental Today, EPA is proposing that the antimicrobial registration submissions. use permit, or tolerance are listed in 40 antimicrobial pesticide requirements be Applicants may save time and money by CFR part 158. codified in a separate subpart W to part understanding when studies are needed. 158 with use patterns (see Unit IV.I. of Having all required studies available to III. Statutory and Historical this preamble) and groups of use EPA at the time of application should Framework patterns specific to antimicrobials. halt potential delays in the registration A. FIFRA Today’s proposed rule is part of a process, thereby enabling registration of Under FIFRA section 3, every series of rules to update all of the data antimicrobial pesticides sooner. pesticide product must be registered requirements for pesticide products. On Products would enter the market faster. October 26, 2007, EPA published in the 3. EPA information assists other with EPA or specifically exempted Federal Register two final rules to communities in assessing pesticide under FIFRA section 25(b) before being promulgate the data requirements for risks. Scientific, environmental, and sold or distributed in the United States. conventional (72 FR 60934), and health communities find antimicrobial Under FIFRA, an applicant for a new biochemical and microbial (72 FR pesticide toxicity information useful to registration or an existing registrant 60988) pesticide chemicals. These rules respond to a variety of needs. For (collectively referred to as applicant in and their proposals (conventional example, medical professionals are this proposal) must demonstrate to the (March 11, 2005) (70 FR 12276) and concerned about the health of patients Agency’s satisfaction that, among other biochemical and microbial (March 8, exposed to antimicrobials; poison things, the pesticide product, when 2006) (71 FR12072)) state the rationales control centers use and distribute used in accordance with widespread for requiring and/or revising particular information on toxicity and treatment and commonly recognized practice, will data requirements. With few exceptions, associated with poisoning; and not cause ‘‘unreasonable adverse these rationales are also applicable to scientists use toxicity information to effects’’ to humans or the environment. antimicrobial pesticide chemicals, and characterize the effects of antimicrobial This safety determination requires the as such have not been repeated in pesticides and to assess risks of Agency to weigh the risks of the use of today’s proposed rule. Today’s proposal pesticide exposure. Similarly, those the pesticide against any benefits. EPA discusses in detail only those revisions responsible for protection of nontarget must determine that the standard for that are singularly applicable to wildlife need reliable information about registration contained in FIFRA is met antimicrobial pesticides, including antimicrobial pesticides and assurance before granting a registration. antifoulants and wood preservatives. that pesticides do not pose an 1. Registration. Section 3 of FIFRA unreasonable threat. The proposed contains the requirements for C. Benefits of this Proposal changes will help the scientific, registration. Specifically, FIFRA section Greater detail on the benefits of this environmental, and health communities 3(c)(2) provides EPA broad authority, proposal is provided in the document by increasing the breadth, quality, and before and after registration, to require entitled ‘‘Economic Analysis of the reliability of Agency regulatory scientific testing and submission of the Proposed Change in Data Requirements decisions by improving their scientific resulting data to the Agency by for Antimicrobial Pesticides’’ which is underpinnings. applicants for registration of pesticide available in the docket for this 4. Better informed users mean products. An applicant must furnish rulemaking (Ref. 44). The following informed risk-reduction choices. Better EPA with substantial amounts of data briefly highlights the anticipated regulatory decisions resulting from the on the pesticide, its composition, benefits: proposed changes should also mean that toxicity, potential human exposure, 1. More refined assessments mean less the label will provide better information environmental properties, and uncertainty and clearer understanding on the use of the antimicrobial ecological effects, as well as information of actual risks. EPA’s current applicator/ pesticide. A pesticide label is the user’s on its product performance (efficacy) in user exposure data base is not direction for using pesticides safely and certain cases. Although the data comprehensive, especially regarding effectively. It contains important requirements are imposed primarily as a exposures to antimicrobials in industrial information about where to use (or not part of initial registration, EPA is and residential settings. The new data use) the product, health and safety authorized under FIFRA section that would be collected once this information to be read and understood 3(c)(2)(B) to require a registrant to proposal becomes final would allow the before using a pesticide product, and develop and submit additional data to Agency to conduct improved pre- and how to dispose of that product. This maintain a registration. post-application exposure assessments benefits users by enhancing their ability 2. Reregistration. FIFRA section 4 for applicators/users, and the general to obtain antimicrobial pesticide requires that EPA reregister each public. This will benefit not only products appropriate to their needs, and pesticide product first registered before workers (including applicators) and to use and dispose of products in a November 1984. This date was chosen consumers by helping EPA to make manner that is safe and environmentally because pesticides registered after 1984 better informed regulatory decisions sound. Applicators/users may benefit were subject to the part 158 that are neither too stringent nor too from label information based on the data requirements of the 1984 regulation.

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00004 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59385

EPA has completed the reregistration/ reviews to risks and benefits, ensuring a determination of ‘‘reasonable certainty tolerance reassessment process for food- efficacy, and meeting review time goals. of no harm’’ under FFDCA are an use pesticides and expects to complete EPA believes that this rule assists in integral part of the data needed for an all reregistration activities by the meeting the section 3(h) mandate. By ‘‘unreasonable adverse effects’’ statutory deadline of August 2008. defining the 12 use patterns for determination under FIFRA. 3. Registration review. FIFRA section antimicrobials in relation to the data Consequently, when promulgated, these 3(g) mandates that the registrations of required for a registration under FIFRA, proposed data requirements would all pesticides are to be periodically EPA is providing clearer and more encompass the basic data requirements reviewed. Changes in science, public transparent information to applicants. for both registration and tolerance- policy, and pesticide use practices occur This should result in submissions to setting determinations. EPA has over time. Through the new registration EPA that contain the required data and authority to require additional data on review program implemented via a therefore can be reviewed and evaluated a case-by-case basis. regulation promulgated on August 9, more expeditiously. 2006 (71 FR 45719) (40 CFR part 155, D. Scope of Proposed Subpart W subpart C), the Agency is periodically B. FFDCA FIFRA contains a number of reevaluating all registered pesticides to FFDCA requires EPA to determine provisions specific to ‘‘antimicrobial assure that they continue to meet the that the level of pesticide chemical pesticides’’ as defined in FIFRA section statutory standard of no unreasonable residues in food and feed will be safe for 2(mm). The statutory definition contains adverse effects. Starting in 2006, human consumption. The safety a complex construction of functionality, registration review began to replace standard set under FFDCA section types of organisms, and intended use to EPA’s reregistration program as the 408(b) and (c) defines safe as ‘‘a describe what is encompassed by the mechanism for systematic review of reasonable certainty that no harm’’ will term ‘‘antimicrobial pesticide.’’ EPA existing pesticides. The registration result from exposures to pesticide believes that the definition was review process begins by reviewing the chemical residues. The combination of primarily intended to be used in available information in the possession aggregate and cumulative exposure conjunction with the provisions of of the Agency and then determining the assessments required by FFDCA section section 3(h), which contains specific data needed for assessing a 408 increases the nature and scope of requirements for process improvements, particular pesticide. Thus, the data EPA’s risk assessment, and potentially timeframes for review purposes, and needed, and the scope and depth of the increases the types and amounts of data other regulatory matters, but, Agency’s review will be tailored to the needed to determine that the FFDCA significantly, does not include specific circumstances of a particular safety standard is met. provisions pertaining to data pesticide. This means that reviews will Under FFDCA section 408, EPA is requirements. The definition in section be commensurate with the complexity authorized to establish tolerances for 2(mm) as it relates to section 3(h) was of the issues associated with each pesticide residues in food and feed, or discussed fully in a proposed rule pesticide. to exempt a pesticide from the issued in the Federal Register of 4. Experimental Use Permits (EUPs). requirement of a tolerance, if warranted. September 17, 1999 (64 FR 50672). Subject to some exceptions, FIFRA In this preamble, references to The statutory definition, however, section 5 requires persons seeking tolerances include exemptions from does not mesh with the Agency’s needs permission for experimental use of a tolerance since the standards and in developing this proposed rule pesticide under controlled condition to procedures for both are the same. The concerning data requirements. Data obtain an experimental use permit. A safety standard applies to tolerances in requirements depend upon the use EUP allows limited use of a pesticide for a number of regulatory situations, pattern, taking into account the specified experimental and data including: pesticide’s hazard and exposure collection purposes intended to support • Tolerances that support registration profiles. How well the pesticide kills or future registration of the pesticide. under FIFRA; repels particular pests are relevant Because a EUP is for limited use under • Tolerances for imported products factors in the determination of product controlled conditions, the data needed which are established to allow performance data requirements. to support issuance of the permit are importation of pesticide-treated Neither FIFRA section 3(c)(2) nor correspondingly less than those commodities, but for which no U.S. section 3(h) requires the Agency to required for full registration. The registration is sought; develop data requirements for an regulations governing the issuance of • Time-limited tolerances which are ‘‘antimicrobial pesticide’’ as defined EUPs are found in 40 CFR part 172. In established for FIFRA section 18 specifically in section 2(mm). Therefore, its final rule ‘‘Data Requirements for emergency exemptions; and the scope of this proposal has been Conventional Pesticides’’ EPA • Temporary tolerances established for expanded beyond ‘‘antimicrobial promulgated subpart C of part 158 to experimental use permits under FIFRA pesticide’’ as defined by FIFRA section contain the data requirements for EUPs, section 5. 2(mm) to include related pesticides that which will be applied on a case-by-case are excluded from the 2(mm) definition. basis to any EUP applications for an C. Linking FIFRA and FFDCA Safety Standards The broader applicability of this 40 CFR antimicrobial pesticide. part 158, subpart W is intended to 5. Registration requirements for Under FIFRA section 2(bb), a ensure that all pesticides currently antimicrobials. FIFRA section 3(h) pesticide that is inconsistent with, or considered as antimicrobial products for requires that EPA evaluate its does not meet, the FFDCA section 408 purposes of FIFRA section 33 fees and registration process to identify safety standard poses an unreasonable review periods are covered. improvements and reforms that will adverse effect that precludes new or Accordingly, this proposal applies to: reduce historical review times for continued registration. Given this • Antimicrobial pesticides, as defined antimicrobial applications. This linkage between registration and in FIFRA section 2(mm). includes defining the classes of tolerances, it makes sense for EPA to • Pesticide products for antimicrobial antimicrobial use patterns and the types define data requirements for both uses in/on food or feed. of application review, conforming purposes: The data required to support • Antifoulant paints and coatings.

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00005 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59386 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

• Wood preservatives. devoted to biochemical (subpart U) and standard under FIFRA and that of • Pesticide products intended to be microbial (subpart V) pesticides. The FFDCA. Accordingly, applicants are manufactured into any of the above. revised data requirements for encouraged to consult with the Agency antimicrobial pesticides would be on the appropriate data requirements, as IV. Introduction to Subpart W incorporated into part 158 as subpart W. proposed here, as related to their A. Data Requirements for Registration specific product prior to and during the C. Subpart W of Part 158 First promulgated in 1984, EPA’s registration process. Subpart W is proposed to be a EPA is continuing its current system pesticide data requirements outline the freestanding series of tables and of identifying the applicability of data kinds of data and related information regulatory text establishing specific data requirements in the data tables. In typically needed to register a pesticide. requirements for each scientific essence, the data requirements illustrate In this proposal, the data requirements discipline for antimicrobial pesticides. the questions the registrant will need to are organized by scientific discipline EPA recognizes that antimicrobial uses answer about the safety of the pesticide (e.g., toxicology), just as the existing are generally different from the uses product before the Agency can register data requirements in part 158 for more typically associated with it. Because of the variety of chemicals conventional, and biochemical and conventional pesticides (e.g., and use patterns, and because EPA must microbial pesticides and those in part agricultural outdoor uses) and therefore retain flexibility to tailor data 161 for antimicrobials. A significant can have different combinations of requirements as appropriate, only change in this proposal from the exposure considerations. The use qualitative descriptors are in the tables. existing data requirements in part 161 is patterns and expected exposures Test notes provide more specific the introduction of 12 use patterns typically determine the data information on the applicability of specific to antimicrobials. Since there is requirements for any pesticide. specific data requirements. much variety in pesticide chemistry, Antimicrobial pesticides are no different The table descriptors NR (not exposure, and hazard, the requirements in this regard from conventional, required), R (required), and CR are designed to be flexible. Test notes to biochemical, and microbial pesticides. (conditionally required) should be the data requirements tables explain the The order of proposed subpart W viewed as a general presentation, conditions under which data are mirrors that of the larger part 158: from indicating the likelihood that the data typically needed. Essentially, the data product chemistry, to efficacy, to requirement applies. The use of R does requirements identify the questions that hazard/toxicity requirements (both not necessarily indicate that a study is the applicant will need to answer human health and ecological toxicity), always required, but that it is more regarding a pesticide product before the to exposure data requirements likely to be required than not. For Agency can register it. Data (application and post-application example, if the applicant wanted to requirements address both components human exposures, and exposure to apply his pesticide to apples, then crop of a risk assessment, i.e., the hazards residues in food), and environmental field trials would be required almost that the pesticide presents, and the fate requirements, which overlap human always on apples. However, if the estimated level of exposure to humans exposure through drinking water. Units physical/chemical properties of the or nontarget species. Having the V–XIV of this preamble describe the chemical did not lend themselves to the appropriate information enables the revisions to the current requirements. test, such as performing an inhalation Agency to understand when those The proposed data requirement tables test with a chemical that is a solid and hazards pose risks. The answer to one are comprehensive. Generally, the data has an extremely low vapor pressure, question may inform the kind of requirements for each discipline are then a waiver might be granted. information needed to answer other discussed separately, but the applicator Generally test notes for R studies questions. For example, a pesticide that and post-application exposure discuss any particular circumstances is persistent and toxicologically potent disciplines are discussed together in a when the testing might not be required. may require more extensive exposure single unit. The use of CR means a study is less data to help establish a safe level of likely to be required. Triggers in the test exposure. In addition, because a number D. Clarifying How to Use the Data notes indicate the circumstances under of antimicrobials are used for public Tables which the Agency has learned through health purposes (for example, Part 158 subpart B contains a step- experience that the information is disinfectants, sterilants, or sanitizers), wise process to assist the applicant in needed. Although only an there are product performance data determining the data needed to support approximation, if percentages were to be requirements to assure that the its particular product. At this time assigned to indicate the need for a antimicrobial product works as subpart B is specific to the needs of particular study, then R could be intended. conventional, and biochemical and viewed as representing the submission microbial pesticides. The process of a study 50% to 100% of the time and B. Structure of Part 158 needed for antimicrobials is no CR would be up to 50%. At this time data requirements for different. EPA is proposing certain Thus, NR, R, and CR are used for conventional, biochemical, and clarifying changes to subpart B to convenience to make the table format microbial pesticides are established in specify the needs of antimicrobial feasible, but serve only as a general 40 CFR part 158. Data requirements for pesticides. Specifically, EPA proposes indication of the applicability of a data antimicrobial pesticides are established to include antimicrobial use patterns in requirement. In all cases, the test notes in 40 CFR part 161. § 158.100 and a reference to the referred to in the table must be Part 158 contains general provisions antimicrobial use site index that will be consulted to determine the actual need concerning all pesticide data (subpart available on the EPA website. for the data. Applicants are also A), instructions on how to use the data While EPA is attempting to assist the encouraged to visit the Agency’s tables that follow (subpart B), and a applicant in subpart B, it is important to website, entitled ‘‘Data Requirements for series of disciplinary data tables that are emphasize that it is the applicant’s Pesticide Registration’’ (see http:// focused on conventional pesticides obligation under FIFRA to demonstrate www.epa.gov/pesticides/regulating/ (subparts C – O). Individual subparts are that an individual product meets the data_requirements.htm). Since it is not

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00006 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59387

possible to sufficiently delineate all There are nine new data requirements While not a new data requirement, circumstances in test notes, consultation for antimicrobials set out in this subchronic dermal testing of end-use with EPA is encouraged. proposal. Two (developmental products has not been routinely The table format includes a column neurotoxicity and immunotoxicity) are required and therefore would be heading entitled ‘‘Guideline,’’ which the same new data requirements as considered a new testing requirement. refers to the OPPTS (Office of Pollution promulgated in the final rule for The circumstances for requiring the Prevention and Toxic Substances) conventional chemicals (72 FR 60934) testing is the same as for conventional Harmonized Test Guidelines. Guideline (see Unit VIII). While photodegradation chemicals. (See Unit VIII). numbers are provided as information/ in soil studies have been routinely Each data requirement proposed in guidance to applicants. These required for conventional chemicals, Units, VIII, IX, X, XII, XIII, and XIV is Guidelines set forth recommended this study would be a new data described as ‘‘new,’’ ‘‘current practices,’’ instructions and test methods for requirement for wood preservatives (see or ‘‘existing.’’ ‘‘New’’ means that the performing a study to generate the Unit XII). Similarly, two new exposure data requirement has never been required data. Since these are guidance data requirements (soil residue required or has rarely been required on documents, the applicant is not required dissipation and non-dietary ingestion a case-by-case basis, and has not been to use these Guidelines, but may instead exposure) are today proposed for routinely considered during the seek to fulfill the data requirement by antimicrobials (see Unit IX.D). Agency’s evaluation of the data needed other appropriate means such as Four new data requirements for the purpose of risk assessment. alternative test methods, submission of (activated sludge sorption isotherm ‘‘Current practices’’ encompasses the an article from open literature, or use of study; ready biodegradability study; data that is typically required to register modeling. The applicant may submit a porous pot study; and modified an antimicrobial pesticide product. This would include existing data protocol of his own devising for the activated sludge, respiration inhibition requirements that are codified in part Agency to review. However, the OPPTS test) are proposed today for 161 as well as those that are not codified Harmonized Guidelines have been antimicrobials that are not included in in part 161 and are now being proposed developed through a rigorous scientific the final rule for conventional for codification in part 158, subpart W. process, including extensive peer pesticides. This is due to the nature of It would also include any study that has review by the FIFRA Scientific Advisory antimicrobial pesticides, which been routinely required on a case-by- Panel. Additionally, many of the includes many down-the-drain uses, i.e. case basis, or any study that is routinely Guidelines have been harmonized those discharged to public treatment considered during the Agency’s internationally. As such, they represent systems, and is discussed in Units XII.B. evaluation of the data needed for the and C. the recommended approach to purpose of risk assessment but is developing high-quality data that Most screening-level environmental infrequently required because the should satisfy EPA’s data needs for risk fate assessments would be performed triggers for that study are infrequently assessment. using the hydrolysis, photodegradation met. in water, activated sludge sorption E. The Nature of Changes to ‘‘Existing’’ requirements are a subset isotherm, ready biodegradability, and Requirements of ‘‘current practices.’’ This particular modified activated sludge, respiration subset means that the data requirement Proposed subpart W does not differ inhibition tests. For wood preservatives, is codified in part 161 and being greatly from the data requirements for the results of the photodegradation in transferred to part 158, subpart W either conventional pesticides promulgated in soil study may also be considered in the ‘‘as is’’ or with specified changes to the October 2007. Where this proposal screening-level assessment. If the test notes, to the Rs, CRs, and NRs, or differs is in the explicit adaptation of porous pot study is triggered based on to the use patterns for which required. those data requirements to the results of the ready biodegradability If there are proposed revisions to an antimicrobials. As previously discussed, study, then those results would also be existing data requirement, then antimicrobial uses were covered in the considered. clarifications on these proposed original (1984) part 158. However part EPA notes that its proposed approach revisions are included in the preamble. 158 (now transitioned for antimicrobials for performing a screening-level fate Such revisions include proposing as part 161) was developed primarily for assessment could potentially result in changes such as a change from agricultural pesticides. Since the use the submission of higher-tiered studies. conditionally-required to required, a patterns which now appear in tables in There are seven higher-tiered change in the number of test species, or part 161 are not specific to environmental fate studies, that could expanding the number of use patterns antimicrobials, often it has been be triggered based on a weight-of- for which the test is required. difficult to discern directly from such evidence evaluation of the results of the As previously discussed, there are tables the data requirements for certain screening-level studies. For example, if frequently consultations to discern data antimicrobials. Without extensive the screening-level assessment were to requirements for certain of the consultation with and interpretation indicate that a down-the-drain chemical antimicrobial use patterns. These from the Agency, frequently it has been would partition to sludge, soil, or consultations have led to general difficult for applicants to effectively use sediment, then higher-tiered understandings as to the data required the tables to determine which data environmental fate studies such as the for a particular use pattern. For certain requirements apply to antimicrobials. aerobic and anaerobic soil metabolism use patterns, all of the studies are Today’s proposal reflects the Agency’s studies may be required. If the chemical considered to be the Agency’s current current needs for risk assessment of would partition to water then higher- practices. As an example, for the wood antimicrobials. Describing the tiered ecotoxicity studies such as the preservative use patterns, there is not a antimicrobial data requirements in fish early life stage may be required. good fit to any of the part 161 use terms of use patterns specific to Thus, the higher-tiered studies that patterns in the tables and therefore the antimicrobial uses provides a clarity could be triggered include both the data needed to register a wood that should reduce the need for environmental fate and ecotoxicity preservative is difficult to interpret from extensive consultations. scientific disciplines. those tables. Given these circumstances,

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00007 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59388 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

EPA developed a series of requirements For ecotoxicity data requirements, the requirements and of potential expansion developed specifically for wood Agency requires a first tier of required of existing data requirements to preservatives. These requirements are data for all antimicrobials regardless of additional antimicrobial use patterns. not codified in CFR, but the applicants the use pattern. The need for higher Applicants and potential applicants for understand that these are the data tiered data depends not only on the new registrations as well as registrants needed for wood preservatives and they frequency, duration, or magnitude of the of existing products may wish to routinely provide these studies to EPA. exposure, but also on the results of the evaluate their products in light of the first tier of the data. F. Tiered Data Requirements proposed requirements. As always, the Such a flexible approach allows EPA Agency encourages applicants to The Agency has organized the to require enough data, but not more consult with EPA, if they have any proposed requirements for antimicrobial than enough, to make the required questions regarding data requirements. pesticide products to support a tiered safety finding. Such an approach is the testing approach. Under such an same as that used for other pesticides; H. Weight-of-Evidence Approach approach the Agency prescribes a however, for antimicrobials the The weight-of-evidence (WOE) specific subset of ‘‘lower tier’’ studies progression from lower to higher tier approach is referenced in several that are conducted first. The results of requirements may differ from that of subpart W test notes. Such an approach this first- or lower-tiered testing are then conventional pesticides because the requires a critical analysis of the entire used in conjunction with exposure data uses and expected exposures are body of available data for consistency or other information to determine the different. and biological plausibility. Some need for more complex ‘‘higher tier’’ considerations in this approach are studies. The risk assessment must G. Impact of this Proposal on Future and Existing Registrations listed below: provide sufficient information to make • Sufficiency of data. Studies that the risk management decisions needed This proposal concerns prospective completely characterize both the effects to register the product or establish a data requirements for future and exposure of the agent have more tolerance. This is a significant factor in registrations of antimicrobial pesticides. credibility and support than studies that the tiering process. That is, these proposed data contain data gaps. Data requirements have been tiered requirements, once final, would apply • Quality of the data. Potentially when EPA believes it can adequately to all new applications for registration relevant studies are judged for quality conduct a risk assessment using a tiered of antimicrobial pesticides submitted and studies of higher quality are given approach. The conditions for after the effective date of the rule. The more weight than those of lower quality. ‘‘triggering’’ these higher tiered studies new data requirements would also • Evidence of causality. The degree of are specified in the test notes to the apply to applications of antimicrobial correlation between the presence of an tables in proposed subpart W. A tiered pesticides that are undergoing Agency agent and some adverse effect is an data submission process is intended to review when the new regulation goes important consideration. allow the Agency to assess a pesticide’s into effect. EPA believes that there may • Corroborative information. risk without requiring the applicant to be a need for some type of a limited Supplementary information relevant to conduct and submit studies that may transition ‘‘window’’ for certain the conclusions reached in the not be needed for the regulatory antimicrobial registration applications. assessment is incorporated, e.g., studies decision. For certain chemicals, data EPA anticipates applicants of demonstrating agreement between from lower tiered requirements may be applications that were submitted, but model predictions and observed effects. sufficient in and of themselves or in not yet approved when the new WOE considers the kinds of evidence combination with other data to address regulations go into effect, may need to available, how that evidence fits the Agency’s risk concerns without discuss with EPA the specifics of their together in drawing conclusions, and submission of higher tiered data application and whether additional time significant issues/strengths/limitations requirements. In other cases, data from may be needed to complete generation of the data and conclusions. WOE is not lower tiered requirements may indicate of certain studies that may then be simply tallying the number of positive that higher tiered data need to be required to fulfill new data or negative studies. provided. The Agency expects requirements. The Agency specifically applicants to consult with the Agency, requests comment on implementing the I. Use Patterns in Subpart W as needed, to determine when effective date of the final rule for The general use pattern groups submission of higher tiered data may be antimicrobials with regards to future described in subpart B of part 158 are required. registrations of antimicrobials. not used as the bases for describing The Agency has tiered the data The Agency does not intend to apply antimicrobial data requirements. Those requirements based on an these requirements automatically or general use patterns were developed for understanding of the potential exposure routinely to all existing pesticide and are appropriate to conventional for a specific use pattern. As an registrations. While EPA intends a pesticide chemicals. example, for toxicology studies used to flexible approach to imposing the new Some years ago, 12 use categories support human health risk assessments, requirements upon existing products, were developed specifically for the high human exposure grouping the Agency may find it necessary to call- antimicrobials. At that time the specifies 19 toxicology studies as in data on certain existing registrations, Agency’s data requirements for all required at the lower tier. The low for example, as warranted by emerging pesticide chemicals were specified by human exposure grouping specifies 13 risks of concern for particular pesticides use patterns developed for and toxicology studies as required. The or as a result of possible future appropriate to conventional pesticide Agency considered the frequency, programmatic changes and priorities on chemicals. To fit antimicrobial uses into duration, and/or magnitude of the existing pesticides, or during this agricultural scheme, the exposure to determine the lower tier of registration review. antimicrobial use categories referred toxicology testing requirements for both However, EPA notes that issuance of back to the then-existing use patterns. the high and low human exposure this proposed rule provides notice to With the Agency’s intention to establish groupings. applicants of potential new data specific data requirements for

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00008 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59389

antimicrobials in subpart W, this • Food storage or distribution exposures via drinking water, as well as referral is no longer needed. facilities. dermal exposures to the treated water. Therefore, the Agency is proposing • Commercial transportation vehicles, • Public water systems. that the use categories employed in shipping, and storage containers. • Individual water systems. recent years to generalize the range of • • Emergency water systems. Food or feed stores and markets. • uses for individual antimicrobial • Vending machines. Water purifier units. • Private water systems of individual pesticide chemicals, now constitute the 3. Commercial, institutional and homes, farms, institutions, camps, use patterns for specifying the industrial premises and equipment. resorts, and industrial plants. antimicrobials data requirements in the This use pattern includes nonfood • Emergency water systems for the tables in proposed subpart W. contact areas of commercial sites. public, campers, travelers, military, and Additionally, EPA is proposing to Typically, antimicrobial pesticides codify in § 158.2201 the specific use fishermen. would be applied to ceilings, doors, 7. Materials preservatives. Materials patterns for antimicrobials. doorknobs, fixtures, floors, light FIFRA section 3(h)(3)(A)(ii)(I) requires preservatives are antimicrobial switches, stairs, walls, windows, and chemicals added during industrial that EPA ‘‘define the various classes of woodwork as part of routine cleaning antimicrobial use patterns.’’ For processes to prevent the growth of practices. Included within this use microorganisms. Examples of such uses antimicrobial pesticides, the Agency pattern are residential school and proposes to structure its requirements include paints, coatings, adhesives, daycare institutions. textiles, and paper. This use pattern by using a system of 12 use patterns This use pattern includes both indoor based on similarity of use, purpose, includes food and nonfood, and mostly and outdoor uses. Some of the uses have indoor uses. pesticidal function, the nature of the the potential for significant exposure exposure, and, in some cases, 8. Industrial processes and water due to the repetitive nature of certain systems. Certain antimicrobial application methods. Today’s proposal exposures and therefore may be meshes with the statutory mandate to chemicals, known as microbiocides, are considered as high human exposure. used to control the growth of bacteria, identify classes of antimicrobial use 4. Residential and public access patterns by defining for each use pattern fungi, and algae in circulating water premises. This use pattern includes systems. There are two types of systems: the data requirements that apply. EPA mostly nonfood areas, although it requests comment not only on the 12 ‘‘once-through’’ and ‘‘recirculating.’’ includes food-handling areas in homes. For ‘‘once-through’’ systems, the antimicrobial use patterns described in Some of the uses have the potential for water is not re-used and is therefore this Unit, but also on the usefulness of significant exposure due to the released into the aquatic environment or these use patterns. EPA also requests repetitive nature of certain exposures a wastewater treatment plant after a comment on whether or not any and therefore may be considered as high single cycle through the system. Once- different/additional use patterns should human exposure. Most uses are indoor. through uses have the potential for be codified by splitting or recombining • Premises, contents, and equipment significant environmental exposure the existing use patterns to make of homes, apartments, mobile homes when the treated water is released to the separate and distinct use patterns. and shelters, including home-based Antimicrobial use patterns also reflect environment. Large volumes of water (as daycare. much as millions of gallons per minute) environmental concerns for indoor • Public areas, public buildings, and versus outdoor use, as well as food may be released directly to a river, public rooms. estuary, or marine environment within versus nonfood-use, and high versus • Commercial kennels, or living low human exposure. The 12 general minutes or hours of adding the quarters of pets, zoo animals, race antimicrobial to the system. In addition use patterns for antimicrobial pesticides horses, or laboratory animals. are described below. Examples within to the potential for environmental 5. Medical premises and equipment. exposure after release, there is the each use pattern are provided: Medical waste is defined as any solid 1. Agricultural premises and potential for high human exposure via waste that is generated in the diagnosis, equipment. This use pattern includes drinking water if the intake pipe for a treatment, or immunization of human many indirect food uses with mostly drinking water treatment plant is beings or animals, in research pertaining indoor use sites. downstream. Also, the water could be thereto, or in the production of • Farm and farm animal premises such used in crop and/or livestock biologicals including, but not limited to, as animal houses and pens (including production thus providing for culture and stocks, pathological wastes, milk houses), parlors, stalls, and barns. additional human exposure. • Transportation vehicles used to human blood and blood products, and However, for many uses of water in transport animals. sharps. This use pattern is considered to industrial plants the treated water is re- • Equipment such as forks, shovels, be indoor nonfood. Some of the uses used repeatedly within the system, scrapers; halters, ropes, other restraining have the potential for repeated exposure ‘‘recirculating’’ in the system multiple equipment; racks, mangers, feeders, and therefore may be considered as high times until released into the aquatic waterers, troughs, and fountains. human exposure. environment or a wastewater treatment • • Food-handling equipment such as Hospital or medical environments plant. EPA has assumed that the milking equipment. such as clinics, dental offices, nursing releases are scheduled as the 2. Food-handling/storage homes, sick rooms, morgues, and antimicrobial has been ‘‘used-up.’’ establishments, premises, and veterinary clinics. Given the lower frequency of release, equipment. This use pattern also • Non-critical medical equipment resulting in lower volumes released to includes many indirect food uses due to such as bedpans, basins, and furniture. the environment, recirculating uses are the treatment of food contact surfaces 6. Human drinking water systems. likely to have less environmental and the resultant human exposures. All Human drinking water systems include exposure than that of once-through use sites are indoor. any methods used to provide potable systems. • Food or feed processing plants. water from raw water supplies. This use As will be explained later in Unit XI, • Eating establishments such as pattern is considered to be high human for the purposes of determining data restaurants and cafeterias. exposure due to the potential for human requirements for environmental fate and

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00009 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59390 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

ecological effects, the industrial • Structures and dwellings. • 12 general use patterns, suggestions processes and water systems use pattern • Transportation vehicles (truck beds for different/additional use patterns, will be subdivided. Because of the and support structures). and their utility. distinct differences between the once- • Crop containers. • Proposed new down-the-drain through and recirculating water • Lawn furniture and decks. requirements. systems, the once-through water system • Playground equipment. Additionally, in other parts of this will be grouped with those use patterns • Garden/landscape timbers. proposed rule, EPA is specifically with potential for higher environmental • Log homes. requesting comments on certain issues. As appropriate during the exposures and the recirculating water 11. Swimming pools. Products in this development of this proposal, EPA has system with those use patterns with the use pattern are used to prevent/control occasionally shared information with potential for lower environmental the growth of bacteria or algae in the the regulated community on the data exposures. water systems of swimming pools, requirements that were under 9. Antifoulant paints and coatings. Jacuzzis, and hot tubs. This use pattern consideration. Commenters are Antifoulants are coatings and paints is considered to be high human applied to boat hulls and bottoms, crab encouraged to comment on such sharing exposure. Under routine use little or no and lobster pots, and underwater of information as part of the environmental exposure is expected, as structures or equipment to control the administrative process of developing the water in swimming pools, Jacuzzis, growth of freshwater or marine fouling this proposed rule. or hot tubs is considered to be separated organisms. Antifoulant coatings have The Agency welcomes comments on from the natural environment. However, the potential for high environmental the following topics of particular when draining is needed, depending on exposure most particularly for marine interest to the Agency: the volume of water and the location of (both freshwater and saltwater) • All aspects of the administrative the pool or hot tub, it is most likely that environments. process used to develop this proposed Also included within this use pattern discharge would be down-the-drain to a rule including outreach activities. is ballast water, that is, the water that is wastewater treatment plant, to a storm • The need for, value of, and any pumped in and out of ballast tanks as drain that discharges to a stream, or alternatives to, the data requirements a ship’s weight changes due to loading directly to soil. described in this document. and unloading of cargo. Ballast water 12. Aquatic areas. Products in this use • The scientific basis of this proposed provides needed stability for safe pattern are designed to control or kill rule. operation of marine vessels. In recent slime-forming bacteria, fungi, or algae in • The clarity of the proposed data years there have been significant lakes, ponds, streams, drainage ditches, requirements for antimicrobial concerns about transport of marine and other bodies of water. In addition to pesticides and the relationship between species from one marine environment to the potential for environmental the proposed data requirements and another in ballast water. When exposure, there is the potential for high EPA’s statutory determinations. discharged into a new environment, the human exposure via drinking water if • The economic analysis of the new species may become invasive and the intake pipe for a drinking water proposed rule, as well as on its disrupt the native ecology. Ballast water treatment plant is in a lake or underlying assumptions, economic data, treatments (such as adding an downstream, or through recreational and high- and low-cost options and antimicrobial to the ballast water before activities such as swimming. Also, the alternatives. discharge) are intended to prevent this. water could be used in crop and/or Commenters are encouraged to The Agency has reviewed few livestock production thus providing for present any data or information that applications for ballast water additional human exposure. should be considered by EPA during the treatments, presumably because J. Use Site Index development of the final rule. Describe treatment of ballast water to prevent the any assumptions and provide any transfer of microorganisms from one As part of this action, the Agency is technical information and data used in marine environment to another is proposing to place on its website an preparing your comments. Explain relatively new. Since ballast water Antimicrobial Use Site Index similar to estimates in sufficient detail to allow for treatments also have the potential for the existing Pesticide Use Site Index at them to be reproduced for validation. high exposure to the aquatic (both http://www.epa.gov/pesticides/ EPA’s underlying principle in freshwater and seawater) environment, regulating/usesite/index.htm. developing the proposed revisions has EPA has grouped the ballast water Information similar to that which would been to strike an appropriate balance treatment pesticide chemicals with the be included on the Antimicrobial Use between the need for adequate data to antifoulant coating pesticide chemicals. Site Index is included in the docket for make the statutorily mandated 10. Wood preservatives. Wood this action (Ref. 41). The existing determinations and informed risk preservative products are those which Pesticide Use Site Index will be re- management decisions, while claim to control wood degradation titled, the Pesticide Use Site Index for minimizing data collection burdens on problems due to fungal rot or decay, Conventional, Biochemical, and applicants. Microbial Pesticides to distinguish it sapstain, molds, or wood-destroying V. Product Chemistry insects. This use pattern has the from the Antimicrobial Use Site Index. The Agency proposes to apply the potential for high exposure for both K. Request for Comments humans and the environment with product chemistry data requirements for mostly outdoor use sites. Certain uses The Agency invites the public to conventional pesticide chemicals, in can be food-uses. The types of wood and provide its views and suggestions for subpart D, to antimicrobial products. the products that can be manufactured changes on all of the various proposals These requirements were promulgated with this treated wood are: in this document. Specifically included in the final rule on October 26, 2007, (72 • Freshly cut logs or lumber. within the Agency’s request for FR 60934). Product chemistry • Seasoned building materials. comments are the following proposals: requirements identify the basic identity, • Utility poles, fence posts and rails. • SAR white paper. and chemical and physical • Structural members. • Four case studies. characteristics of a pesticide chemical.

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00010 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59391

These data, to a limited extent, are used explicit what antimicrobial claims data requirements are discussed in Unit to determine if a pesticide contains would be considered public health VIII of this preamble. contaminants which are of toxicological claims for purposes of product For EPA to assess the potential risks or environmental concern and are performance data submission. that antimicrobial products pose to necessary to determine proper label At the time of application, EPA humans, it is necessary not only to precautions. Product chemistry requires the submission of product assess the hazard of the antimicrobial requirements are generally not performance data for products making a active ingredient based on toxicology dependent on a pesticide’s intended use public health claim. An application will information, but also to estimate human pattern, and therefore it is appropriate not be approved in the absence of exposures to the antimicrobial based on to apply the same requirements to acceptable data substantiating a public the product use patterns. For antimicrobial pesticides as required for health claim. EPA requires the antimicrobials, three types of exposure conventional pesticides. If development of product performance data are required: applicator, post- circumstances particular to data for all other (non-public–health) application, and residue chemistry antimicrobial pesticides should arise, products, but does not review or (which includes exposure via food and then the Agency has the authority to approve such data as part of a new or water). require the appropriate product amended registration. If, after the Applicator and post-application chemistry data on a case-by-case basis. product has been registered, EPA has exposure data are used to evaluate VI. Product Performance Data reason to review such data (for example, exposures to persons in occupational Requirements there are indications that the product and non-occupational settings, does not perform as claimed), then EPA EPA is not proposing to revise including residential, commercial, will require the registrant to submit product performance data requirements institutional, and recreational sites. such data within a reasonable time. A (§ 158.2220) at this time. At this time Exposure data include: dermal and request for submission of product there are nearly identical product inhalation exposure data for applicators, performance data after product performance data requirements for post-application residue data, post- registration is not required to be done antimicrobial chemicals in both application monitoring data, use under the Data Call-In provisions of § 158.400 and part 161. EPA proposes to information, and human activity FIFRA section 3(c)(2)(B), but is instead transfer the contents of the existing information. Applicator and post- authorized by regulation. product performance data requirements application data requirements are for antimicrobial pesticides into subpart Accordingly, if an antimicrobial discussed in Unit IX of this preamble. W, specifically § 158.2220. The table is product makes a claim to control Residue chemistry information is transferred essentially unchanged. EPA microorganisms that pose a threat to used to establish tolerances for residues is also proposing to delete the human health, the applicant is then of pesticide chemicals (and any duplicative data requirements for required to submit product performance metabolites of concern) in/on food antimicrobials from the table in data to support its registration. The crops, processed foods, and animal § 158.400. After the publication of the types of product performance data products consumed by humans when final rule, all product performance data required by the Agency to support the animal consumes a feed item requirements for antimicrobials will be registration of an antimicrobial are derived from these crops. The Agency contained in § 158.2220. determined by the types of claims made estimates the dietary exposure of the In the Federal Register of September on the product’s label (e.g., sanitizer, general population and various 17, 1999, (64 FR 50726), EPA published disinfectant) and the intended use site population subgroups to pesticide a proposed rule entitled, ‘‘Registration for the product (e.g., hard surface, residues in food by using the residue Requirements for Antimicrobial fabric). data as inputs to the dietary modeling. Pesticide Products and Other Pesticide VII. Human Health Risk Assessment The dietary exposure is then used in Regulatory Changes.’’ In that proposed conjunction with toxicity data to rule, EPA proposed various definitions The data needed to conduct a human determine risk. Residue chemistry data for public health pesticides. Today, the health risk assessment include both requirements are discussed in Unit X. Agency is re-proposing definitions for toxicology and exposure data. the following terms: disinfectant, Toxicology studies are used to assess VIII. Toxicology Data Requirements fungicide, microbiological water hazards of pesticides to humans and A. Toxicology Data Requirements for purifier, sanitizer, sterilant, domestic animals, and include a variety Antimicrobials tuberculocide, and virucide. These of acute, subchronic, and chronic proposed definitions are identical to toxicity studies; developmental/ EPA proposes to adapt the basic those in the 1999 proposal. The Agency reproductive tests; and tests to assess toxicology data types as listed in is also re-proposing the 1999 criteria mutagenicity and pesticide metabolism. subpart F of current part 158 to support that EPA would use to consider whether To assess human health risk, there must applications for antimicrobial products. a product makes a public health claim. be sufficient information to select the However, EPA also proposes to modify The comments that were received on the appropriate doses and end-points, i.e., the applicability of those requirements 1999 proposed rule were considered for the Agency must know the level of to reflect the differing risks of and levels today’s proposed rule. exposure at which an adverse effect is of exposure to antimicrobials. The current regulations in part 161 observed. This requires a toxicological As with conventional pesticides, the require that each applicant must ensure database that is not only complete in the types of toxicology studies required for through testing that its products are endpoints it covers, but is also of antimicrobials can include acute, efficacious when used in accordance acceptable quality. The duration of the subchronic, and chronic toxicity with label directions and commonly toxicity study approximates the studies, as well as carcinogenicity, accepted practices. The requirement to estimated duration of the human prenatal developmental toxicity, submit product performance data is exposure, while considering species reproductive toxicity, mutagenicity, directly linked to making a public differences in maturational milestones neurotoxicity, immunotoxicity, and health claim. Today’s proposal makes and overall life span. The toxicology other studies.

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00011 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59392 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

1. Acute toxicity studies provide toxicity data for antimicrobials. In 1987, testing. There are many factors that information that serves as a basis for based on its evolving understanding of could affect the testing progression. classification and precautionary labeling antimicrobial uses, the Agency issued Rather, decisions regarding the and the need for child resistant an Antimicrobial Toxicology Data Call- sequence in which the tests are packaging. In (DCI) Notice (52 FR 595, January 7, conducted are left up to the applicant. 2. Subchronic toxicity studies provide 1987) (Ref. 24), which specified a tiered Thus, the applicant has flexibility to information that can be used to assess approach for submission of toxicology determine the sequence of testing, as human health hazards that may result and human exposure data. best suited for their particular chemical. from repeated exposures to a pesticide The 1987 Antimicrobial Toxicology Early consultation with the Agency is over a limited period of time. These data DCI divided antimicrobial pesticides recommended to attain a common also provide information for selecting into three exposure categories: low, understanding of the sequencing that proper dose levels for chronic/ medium, and high. The toxicology data should be used. required was tiered according the carcinogenicity studies. C. Groupings for Antimicrobial 3. Chronic toxicity studies are used to amount of exposure. The first tier Toxicology Data Requirements assess potential hazards resulting from toxicology data requirements (low prolonged and repeated exposures to a exposure) were the standard acute 1. Overview. This proposal divides the pesticide over a significant portion of studies, a 90–day dermal or inhalation antimicrobial uses into two groups, high the life span. study, a prenatal developmental toxicity human exposure and low human 4. Prenatal developmental toxicity study in one species, and a battery of exposure uses. Because high human studies are designed to assess the mutagenicity studies. The second tier exposure uses may pose higher risks, potential of a pesticide to induce effects (medium exposure) included the first- more toxicology studies are required in offspring as the result of exposure of tier toxicology studies and a subchronic than for uses with less exposure. For the the mother during pregnancy. feeding study, a prenatal developmental purpose of determining toxicology data 5. Multigeneration reproduction study in a second species, and a dermal requirements, high human exposure is studies are designed to provide absorption study. The third tier (high defined as that resulting in human information concerning the general exposure) included the first- and exposures over a considerable portion of effects of a pesticide on overall second-tier studies and the chronic the human lifespan. Exposure to food reproductive capability. feeding, carcinogenicity, reproduction, and water, which occurs throughout the 6. Mutagenicity studies assess the and metabolism studies. All food-use human life span, is therefore a high ability of the pesticide to interact antimicrobials were considered high human exposure. For other exposures directly or indirectly with cellular DNA, exposure. such as occupational and residential, RNA, proteins, or chromosomes and the Applicants could fulfill the toxicology the Agency has considered the potential for adverse effects on cellular data requirements by submitting the frequency, duration, or magnitude of the genetic material. appropriate toxicity studies or by exposure to determine in its best 7. Neurotoxicity studies evaluate the submitting a combination of toxicity professional judgment if the exposure is potential of the pesticide to adversely studies and exposure data. The Agency high. One or a combination of these affect the structure and functions of the used the exposure data and submitted parameters led the Agency to make the nervous system. toxicology data to determine whether determination that the exposure is high. 8. Immunotoxicity studies evaluate and which additional toxicology studies As an example, swimmers may swim the potential of the pesticide to were needed to assess the hazard of the daily or weekly, from several minutes to adversely impact the immune system. antimicrobial. several hours with almost their entire 9. Metabolism studies evaluate the In proposing part 158, subpart W, the body in the water. There are workers absorption, distribution, Agency is specifying the toxicology data who manually pour concentrates into biotransformation, and excretion of the requirements it believes are appropriate vessels for mixing (with water or other pesticide. for specific antimicrobial use categories, chemicals) in order to prepare dilute drawing upon EPA’s experience since B. The History of Toxicology solutions for use. Such exposures can 1987. EPA is now proposing two Requirements for Antimicrobials occur daily, weekly, monthly, or groupings: Low- and high-exposure. In episodically as dictated by the By 1984, the Agency had reconsidered practice, the submission, review, and circumstances of the job. Particularly in its toxicology data requirements for all evaluation of toxicity data merged the the absence of personal protective pesticides, including antimicrobials. For low- and medium-exposure categories. equipment, these workers have the instance, it had become clear that Therefore, the low- and medium- potential for high dermal and inhalation exposure to antimicrobial pesticides exposure categories from the 1987 DCI exposures. Accordingly, for the might well be long-term and frequent were combined to create what is today purposes of defining data requirements, since many antimicrobials were used the low exposure category. EPA proposes to categorize food and indoors in close proximity to humans. Today’s proposed approach feed uses and certain nonfood-uses as Occupational users often were exposed conceptually follows the tiering high human exposure. to concentrated antimicrobial products approach used in 1987. Generally, data As discussed, the Agency considers while mixing and diluting the product requirements proceed in a tiered high human exposure uses to be those for use, and might be exposed to an manner from simpler to more complex that could result in pesticide residues antimicrobial pesticide for large studies considering the frequency, occurring in food or feed, or in drinking portions of their working lifetimes. In duration, and magnitude of exposure as water. These would include, but are not response to the reregistration program well as the dermal absorption of the limited to: initiated under the 1988 amendments to pesticide. Knowledge gained from • Human or animal drinking water. FIFRA, EPA concluded that additional results of assessments performed using • Fruit and vegetable rinses. data were needed to properly evaluate these lower tiered studies is used to • Egg washes. the potential hazards associated with indicate if any higher tiered studies are • Outdoor aquatic uses in lakes, rivers, antimicrobial pesticides. Consequently, required. The Agency does not prescribe or streams which have the potential to the Agency began to require more a required sequence of toxicological contaminate potable water.

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00012 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59393

• Indirect food uses with residues toxicology data requirements requires toxicity studies than would generally be equal to or greater than 200 parts per fewer studies for lower exposures. The submitted are required. Upon request billion (ppb). Agency also works to design study the Agency will provide written • Any use that requires a tolerance or protocols that minimize the guidance concerning exposure, toxicity, tolerance exemption (except for indirect development burden and limit uses of and other data requirements for ‘‘open’’ food uses requiring a tolerance or test animals. Toxicity testing and ‘‘closed’’ MWF systems. tolerance exemption in which residues requirements may be satisfied in a 3. Data requirements for low human are less than 200 ppb). combined study, such as combining the exposure uses. As previously discussed, EPA also considers high human prenatal developmental and the Agency proposes to apply a tiered exposure uses to be those uses that reproductive toxicity testing system to toxicology testing could result in high exposure to requirements in a single study. requirements for low human exposure applicators, and any other antimicrobial However, if this option is chosen, the antimicrobials. The required data are: uses which could result in high protocol must be approved by the Acute oral, dermal, and inhalation exposure to humans. These would Agency prior to the initiation of the toxicity; primary eye and dermal include but are not limited to: study. Details for developing protocols irritation; dermal sensitization; a • Wood preservatives. are available from the Agency. subchronic toxicity study in the rodent; • Metal cutting (metalworking) fluids. 2. Data requirements for high human prenatal developmental toxicity studies • Swimming pools. exposure uses. For high human in two species; a two-generation This list is not exhaustive. There may exposure uses, EPA is proposing to reproduction study; mutagenicity be other uses that the Agency would require the following studies: Acute studies; and immunotoxicity testing. consider high human exposure uses oral, dermal, and inhalation toxicity; Based on the review of these studies, based on their potential for human primary eye and dermal irritation; additional studies may be required if exposure. Low human exposure uses are dermal sensitization; subchronic studies there is evidence of significant toxicity defined as those that are not high in two species; mutagenicity studies; in the submitted studies. Evidence that human exposure uses. acute and subchronic neurotoxicity could trigger concerns may include data The Agency is proposing an approach testing; prenatal developmental toxicity indicating neurotoxicity, that might allow an applicant for studies in two species; a two-generation immunotoxicity, developmental, registration of a pesticide with low reproduction study; a chronic feeding reproductive, or other systemic toxicity human exposure uses to generate fewer study in one species; carcinogenicity such as the presence of neoplastic studies in total than would be required studies in two species; a mammalian growth or significant target organ for high human exposure uses. Under metabolism study; and an toxicity. In such cases, appropriate this proposal, applicants with low immunotoxicity study. Based on a studies to address the Agency’s hazard human exposure antimicrobials may weight-of-evidence evaluation, a or risk concern would be required. The perform tests in a tiered fashion. As developmental neurotoxicity study may table in proposed § 158.2230 contains previously explained, for toxicology be required. If the Agency determines, test notes that explain how these studies the high human exposure based on use information that dermal toxicology requirements are proposed to grouping specifies 19 toxicology studies exposure is the major route of exposure, be applied to low human exposure as required, and for the low human then EPA may require dermal antimicrobials. exposure grouping, 13 toxicology absorption testing or toxicological 4. Data requirements for indirect food studies as required. After the 13 studies conducted by the dermal route. uses. For the purpose of determining required studies for low human i. Wood preservatives. For wood toxicology data requirements, an exposure are reviewed by the Agency, preservatives, the Agency may require antimicrobial use is considered an additional testing may be required for toxicity data on both the active indirect food use when the low-exposure uses based on the result(s) ingredient which is incorporated into antimicrobial pesticide is applied to a of the lower-tiered studies. These 13 the wood and on transformation/ surface or incorporated into a material studies could indicate a low risk degradation products which occur in that may contact food, but is not applied potential or could trigger the need for wood post-treatment. Such directly to food. Residues of the additional data. transformation/degradation products pesticide or its degradates can be The table in proposed § 158.2230 would include dislodgeable residues transferred to the food when it comes presents the toxicology data (i.e., residues that occur from hand into contact with these treated surfaces requirements. The proposed toxicology contact with treated wood) or leachate and articles. Examples of antimicrobial data requirements for the two groupings residues (i.e., residues that occur in soil uses which may result in residues in (high human exposure and low human or water in contact with treated wood). food, through normal use, are sanitizers exposure) are separated into two ii. Metal working fluids (MWFs). and disinfectants, which may be used in columns showing test by test whether it While both ‘‘open’’ and ‘‘closed’’ MWF food-handling areas, but not directly is typically required (shown as R) or systems are high human exposure uses, applied to the food. conditionally required (shown as CR). under the appropriate circumstances, With the passage of the Food Quality The Agency recognizes that the Agency distinguishes between Protection Act of 1996 (FQPA), as later toxicology testing can represent a large ‘‘open’’ and ‘‘closed’’ systems. Fewer modified by the Antimicrobial burden on applicants and can involve toxicity data may be required for a Regulation Technical Corrections Act of significant animal testing. ‘‘closed’’ system. If the use of the MWF 1998 (ARTCA), EPA currently has the Consequently, the Agency works with is limited to ‘‘closed’’ systems only, the responsibility for establishing tolerances applicants, the scientific community, applicant clearly identifies the use as or tolerance exemptions for all pesticide and other stakeholders to ensure that such, and the Agency agrees, then fewer uses that result in residues in or on data requirements produce the toxicity studies would be required for food, except for: information needed to enable the that ‘‘closed’’ system. Based upon • Residues that result from the use of Agency to make the safety findings review and evaluation of the submitted antimicrobial substances on food or in required under FIFRA and FFDCA. The toxicity studies and exposure data, EPA water that comes into contact with food, tiering process proposed within the may determine that fewer additional if such substances are used where food

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00013 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59394 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

is prepared, packed, or held for between high and low human 12276), and in the final rule preamble commercial purposes. (For raw food exposures. Antimicrobials used in a (October 26, 2007) (72 FR 60934). That commodities, this exclusion does not manner which results in residues in rationale is also applicable to apply if the antimicrobial is applied in food from an indirect use that are equal antimicrobial pesticide chemicals. a facility where only such foods are to or greater than 200 ppb would be EPA proposes to adopt the current treated and the treatment of the foods considered high exposure uses. The conventional pesticide data does not constitute food processing.) Agency specifically requests comment requirements for neurotoxicity testing to • Antimicrobial substances used as on the use of 200 ppb residues in food antimicrobials. Adopting the battery of food contact substances in or on food, as the differentiation between the high two neurotoxicity studies would codify such as those used in the manufacture and low human exposure for the the Agency’s current practices. of food contact packaging. This purposes of subpart W. The current adult neurotoxicity test exclusion does not apply to objects For indirect food uses, the applicant battery for antimicrobials in part 161 impregnated with a food contact should begin the process by collecting consists of three studies: Acute delayed substance (other than food packaging all available information. Since many neurotoxicity (hen), 90–day material) if the inclusion of the indirect food uses were previously neurotoxicity (hen), and 90–day substance is intended to have an evaluated by FDA, there may be a neurotoxicity (mammal). The mammal antimicrobial effect on the food contact petition that was submitted to FDA. For subchronic neurotoxicity study is surface of the object. some chemicals, toxicity testing may required if the acute oral, dermal, or FDA has the responsibility for have been conducted and reviewed in inhalation toxicity studies show regulating these antimicrobial the open literature. After identifying the neurotoxicity or neuropathy. The substances as food additives under available reliable information, the existing required data are inadequate for section 409 of the FFDCA. However, applicant should compare this evaluating neurotoxic effects of some under the provisions of FIFRA section information to the data requirements in chemicals. 2(bb) prior to registration of a pesticide the appropriate column in the table in The proposed battery of two studies that may result in residues of that § 158.2230. If the applicant believes that in the rat is more sensitive than the pesticide in or on food (including an existing study satisfies the data neurotoxicity tests currently required in sanitizers, disinfectants, and requirement, then this should be part 161. The objective of the proposed slimicides), EPA must make a safety discussed with EPA. acute and subchronic neurotoxicity finding that the pesticide residue meets The applicant is also encouraged to battery is to evaluate the incidence and the standard set forth in section 408 of review the approach discussed in Unit severity of the functional and behavioral FFDCA. This applies even if FDA will XVIII.A. of this preamble on the use of effects, the level of motor activity, and establish a food additive regulation for Structure-Activity-Relationship (SAR) the histopathology of the nervous the use of the antimicrobial substance assessments to ascertain if such system following exposure to a pesticide under section 409 of the FFDCA. techniques could provide useful chemical. Since publication in 2002 of its final information in preparing a submission Under this proposal, an adult guidance for toxicology to EPA. neurotoxicity test battery of two studies recommendations for food contact would replace the current battery of substances, FDA has used an approach D. Acute Toxicity Studies for End-Use three studies. The two studies are an with several tiers: residues less than 0.5 Products acute and a subchronic 90–day ppb, between 0.5 and 50 ppb, between EPA proposes to add a test note to neurotoxicity study in rats. The acute 50 ppb and 1,000 ppb, and greater than clarify that the currently required six study would detect possible neurotoxic 1,000 ppb. EPA recognizes the historic acute toxicity studies are to be effects resulting from a single exposure. usefulness of the FDA’s tiered approach conducted on the product as formulated The subchronic study would detect and proposes to adopt it conceptually, for sale and distribution. These six acute possible effects resulting from repeated but with a modification appropriate to studies may also be needed for the exposures. These studies were antimicrobials (biocides). FDA’s product as diluted for use. Many presented to the FIFRA SAP in 1994, guidance (Ref. 8) specifically antimicrobial products are diluted at the which endorsed them, and the Agency recommends that a factor of 5 be used point of use, but can still lead to has generally required them on a case- to account for the toxicity of biocides. significant exposure. The applicant has by-case basis since 1992 for all Further modifications to this approach the option of also conducting certain pesticides, including antimicrobial are needed for EPA to perform an studies using the highest diluted pesticides. assessment of risk that conforms to the concentration (i.e., the least diluted The required parameters for a FFDCA section 408 safety finding which product) permitted by the labeling. This subchronic neurotoxicity study may be now requires consideration of the ‘‘... test note codifies EPA’s current incorporated into the standard 90–day special susceptibility of infants and practices. Consultation with the Agency subchronic feeding study in rats. The children to the pesticide chemical is highly suggested to assure that the acute and subchronic neurotoxicity residues....’’. Thus, additional studies appropriate product and any studies in adult rats, in addition to are needed even for the lower exposures appropriate dilutions are tested. providing data on the potential for for which FDA historically would not adverse neurotoxic effects, may also have required data. E. Neurotoxicity provide a basis for comparing the Accordingly, EPA proposes to classify EPA promulgated toxicity potential for age-related differences in indirect food uses of antimicrobials requirements for conventional pesticide impacts on the nervous system if a which result in residues in or on food chemicals, in which the data developmental neurotoxicity study is of less than 200 ppb as low human requirements for neurotoxicity were triggered for the same chemical. exposure uses for purposes of subpart revised. The former test battery of three For high human exposure uses, EPA W. Given FDA’s historical experience studies was revised to include only two proposes to require both the acute with biocides, EPA believes that the 200 studies. The rationale for those revisions neurotoxicity and subchronic ppb (1,000 ppb divided by 5) was discussed in Unit XI of that neurotoxicity studies in the rat. For low benchmark is a reasonable delineation proposed rule (March 11, 2005) (70 FR human exposure uses, both

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00014 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59395

neurotoxicity studies are proposed to be Just as with conventional pesticides, sanitizer application to a hard surface conditionally required (CR) and would the Agency is proposing to require such as a desktop. Thus, there is a be triggered if there is evidence of subchronic dermal testing of the end- greater potential for the applicator to be neurotoxic effects in the 90–day oral use product if the product or any exposed to large amounts of pesticide. study in rodents or if other data show component of the product may increase In addition, many of the components of evidence of neurotoxicity. dermal absorption of the active HVAC&R systems are typically ingredient(s) or could potentiate toxic or F. 90–Day Oral Studies inaccessible and could create unique pharmacologic effects. Testing of an exposure scenarios for applicators. Post- EPA proposes to adopt the current end-use (formulated) product in either application exposure to building conventional pesticide data of these studies has not been routinely occupants is also a concern. When the requirements for subchronic (90–day) required and therefore would be a new treated system resumes operation, the studies to antimicrobials. Oral 90–day testing requirement for antimicrobials. potential exists for the pesticide to be toxicity studies in two species are A test note has been added to both of readily spread throughout the building. currently required in part 161 for high these existing data requirements to For these reasons, the Agency is human exposure uses and conditionally describe the triggers for end-use product proposing to modify the requirement for required in part 161 for low human testing. 90–day subchronic studies to address exposure uses. The Agency is proposing Currently, end-use products are HVAC&R uses. Specifically, the Agency to continue this existing requirement for required to be tested for acute dermal is proposing to replace the 90–day oral high human exposure uses in part 158, toxicity and dermal irritation. Without toxicity test with two 90–day toxicity subpart W. The Agency is proposing to additional subchronic testing of the end- tests, one by the dermal route, and one require an oral 90–day study in one use product, risk from dermal exposure by the inhalation route. These are the species (rodent) for low human to an end-use product may be primary routes of exposure from exposure uses and to conditionally underestimated for those products that HVAC&R uses, and such route-specific require testing in a second species (non- contain an inert ingredient that studies are intended to provide the rodent). For low human exposure uses, increases the dermal absorption of the Agency with the information needed to this change from two conditionally active ingredient. An example of such characterize the hazard for the risk required studies to one required and one an inert ingredient would be dimethyl assessment for HVAC&R uses of conditionally required study would sulfoxide. antimicrobial pesticides. codify current practices. H. 90–day Dermal and 90–day Often, range-finding studies of at least I. Chronic Studies 90 days are needed to select the Inhalation Testing for HVAC&R Uses appropriate dose levels for the mouse Heating, ventilation, air conditioning, Currently in part 161 a chronic carcinogenicity study. Thus, 90–day and refrigeration systems (collectively toxicity study in two species is required studies are often performed routinely by referred to as HVAC&R) refer to systems for all food-uses and conditionally most investigators prior to the initiation which refrigerate, exclusively air required for all other use patterns. of the carcinogenicity study. Often the condition, or exclusively heat, as well as Today the Agency is proposing to range-finding studies have been those in which one system provides continue this existing requirement by submitted to the Agency for review. both heating and cooling. HVAC&R requiring a chronic study in the rodent Because of their utility in determining systems are present in industrial, for high human exposures and the dose levels in the mouse institutional, commercial, and conditionally requiring the study for carcinogenicity study, in the test notes, residential establishments, and include, low human exposures. the Agency encourages the use of range- but are not limited to: air ducts, duct In its final rule for conventional finding studies in the mouse. fittings, duct liners, fans, supply ducts, pesticide chemicals, the Agency Additionally, all 90–day subchronic return ducts, exhaust ducts, intakes, eliminated the requirement for an oral studies in the rodent can be designed to outlets, louvers, diffusers, dampers, chronic study in a second, non-rodent simultaneously fulfill the requirements plenums, outdoor air intakes, air species, usually the dog. Similarly, EPA of the 90–day neurotoxicity study by handling units, and any other ductwork is proposing to eliminate the 1–year dog adding separate groups of animals for and similar components. The Agency is study as a data requirement for testing. Although the subchronic concerned with potential exposures and antimicrobial pesticides. EPA’s guidelines include the measurement of risks from application of antimicrobial reasoning is fully explained in the final certain neurological endpoints, they do pesticide products used to treat the rule (Unit X) for conventional pesticides not meet the requirement for a 90–day surfaces of HVAC&’s system (Refs. 36, 37, and 38). For antimicrobials neurotoxicity study. components. An example of such EPA would adopt the same criteria (as treatment would be use of an set out in the applicable test note to the G. 21/28–day Dermal and 90–day antimicrobial as part of air duct table in proposed § 158.2230) for the Dermal Testing with End-Use Product cleaning. rare circumstances when a 1–year dog Currently in part 161 there is a HVAC&R is a unique use site which study might be required. conditional requirement for 21–day must be specifically identified on the J. Carcinogenicity Studies and/or 90–day dermal toxicity studies label of the antimicrobial product. The for all use patterns. The Agency is application of an antimicrobial product Currently in part 161 two proposing to continue to conditionally to an HVAC&R system represents a use carcinogenicity studies are required for require 21/28–day and/or 90–day pattern substantially different from all food-uses and conditionally required dermal toxicity studies for all other hard surface disinfection or for all other use patterns. Today the antimicrobials. As determined by the sanitizer treatments. Application to Agency is proposing to continue this Agency, based on the use pattern, HVAC&R systems may require that existing requirement by requiring frequency of exposure, and magnitude larger volumes of the antimicrobial be carcinogenicity studies in two species of exposure, the 21/28 day study may applied to both internal and external for high human exposures and provide the appropriate information for system components than would conditionally requiring the studies for risk assessment purposes. typically be used as a disinfection/ low human exposures.

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00015 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59396 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

K. Prenatal Developmental Toxicity portion of the FIFRA SAP in June 1997 1. The antimicrobial pesticide causes The Agency proposes to require two (Ref. 13). Although the SAP did not treatment-related neurological effects in comment on this analysis, the Agency adult animal studies, such as: oral prenatal developmental toxicity • studies (one in rodents and one in a determined that a reproductive toxicity Clinical signs of neurotoxicity. study would ensure that it did not miss • Neuropathology. non-rodent species) to support the • Functional or behavioral effects. registration of every antimicrobial potential reproductive risks of concern. In making the safety finding under 2. The antimicrobial pesticide causes pesticide product. This not only codifies treatment-related neurological effects in the Agency’s current practices, but also FFDCA, the Agency is required to consider the special susceptibility/ developing animals, following pre- or harmonizes the requirements for post-natal exposure such as: antimicrobials with those of sensitivity of infants and children to • pesticide chemical residues. EPA cannot Nervous system malformations or conventional pesticides. neuropathy. The Agency encourages applicants for adequately characterize the • susceptibility of infants and children Brain weight changes in offspring. registration to consider the use of • Functional or behavioral changes in without a reproduction and fertility combined study protocols in satisfying the offspring. effects study that assesses the this requirement. A prenatal 3. The antimicrobial pesticide elicits occurrence of biologically adverse developmental toxicity study segment a causative association between effects on the male and female could be added to a two-generation exposures and adverse neurological reproductive system, as well as on the reproduction study in rodents. By effects in human epidemiological developing organisms from exposure combining protocols, a single study studies. could satisfy the requirement for both prior to conception (either parent), 4. The antimicrobial pesticide evokes prenatal developmental and during prenatal development, or post- a mechanism that is associated with reproductive toxicity in the rodent. natally in the offspring up to the time adverse effects on the development of While it is recognized that the cost of of sexual maturation. Thus, to make the the nervous system, such as: the reproduction study would increase safety finding requires reproduction • SAR relationship to known somewhat due to the additional work testing, since reproductive toxicity neurotoxicants. scope, the total cost of the combined testing endpoints are not adequately • Altered neuroreceptor or study would be substantially less than assessed in the other required toxicity neurotransmitter responses. that incurred by conducting the two studies. Therefore, these other studies EPA proposes the addition of the studies separately. Moreover, a do not provide adequate ‘‘triggers’’ developmental neurotoxicity study to combined reproduction/developmental which would indicate the potential for the toxicology testing requirements as a protocol should not require the use of reproductive toxicity. conditional requirement. The two additional animals and would increase Today’s proposal harmonizes the required developmental toxicity studies the efficient utilization of the animals requirements for antimicrobials with do not include an in-depth assessment being studied. The second required those of conventional pesticides. EPA of the development of the nervous prenatal developmental toxicity study has been requiring a reproductive system and therefore do not provide the in the non-rodent would then be toxicity study for all antimicrobials for same information as the DNT. In performed separately. the last several years. implementing this conditional The Agency may require an additional As noted in Unit VIII.K. of this requirement, applicants are encouraged prenatal developmental study by preamble, the prenatal developmental to apply what is known about the another route of exposure (usually and reproductive toxicity testing chemical and its toxicity to develop a dermal) if there is evidence of requirements may be combined in a rational, science-based approach to this developmental toxicity in any of the single study. If the applicant does not testing. available studies and the other route of choose this option, then separate N. Mutagenicity exposure is, in the Agency’s judgment, developmental and reproductive a significant route of exposure (Refs. 3, toxicity studies must be conducted. Mutagenicity testing is required in part 161; however, just as with 18, and 35). Submission of such a study M. Developmental Neurotoxicity (DNT) is an infrequent occurrence: only one conventional pesticide chemicals, the dermal prenatal developmental toxicity In practice, EPA evaluates each Agency is proposing to change the study has been submitted for an pesticide using all available specific types of tests to be performed to antimicrobial. toxicological information that might satisfy the mutagenicity testing indicate a need for a developmental requirement (Refs. 4 and 26). A battery L. Reproduction neurotoxicity study. The DNT study has of mutagenicity tests is currently The Agency proposes to require a been required on a case-by-case basis for required in part 161 to assess the reproductive toxicity study to support certain conventional chemicals for food- potential of the test chemical to the registration of every antimicrobial use and nonfood-use registrations since adversely affect the genetic material in pesticide product. This codifies the 1991. the cell and subsequently serve as part Agency’s current practices. Just as with conventional pesticide of the Agency’s weight-of-evidence For many years, for nonfood-uses, the chemicals, the Agency is now proposing approach for classifying potential Agency did not require a reproductive that DNT testing be conditionally human carcinogens. Mutagenicity data toxicity study for low human exposure required for all antimicrobial pesticides. are also used to evaluate potential antimicrobials. However, in 1997, it was This would be a new requirement for heritable effects in humans. suggested that, without a reproductive antimicrobial pesticides. The study is Mutagenicity testing would no longer be toxicity study, the Agency could be triggered based upon a weight-of- subdivided into the categories of gene missing reproductive risks of concern. evidence evaluation of the toxicological mutation, structural chromosomal For example, the Pest Management database. The criteria involved in this aberrations, and other genotoxic effects, Regulatory Agency (PMRA) of Canada, weight-of-evidence evaluation are the with selection from a wide range of presented the results of a retrospective same as those for conventional pesticide mutagenicity tests satisfying these analysis during the public comment chemicals and are presented below: categories.

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00016 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59397

For conventional pesticides, the requirements have been modified exposures and conditionally requiring Agency requires in § 158.500 an initial accordingly. the study for low human exposures. battery for mutagenicity testing that Since there are many different Q. Companion Animal Safety consists of a bacterial reverse mutation mutagenicity tests available besides assay with Salmonella typhimurium those in the initial battery, other types Currently in part 161 a domestic and Escherichia coli, an assay with of testing may have been performed in animal safety study is conditionally mammalian cells in culture, and an in the course of product research and required. According to the test note in vivo cytogenetics assay. The Agency has development. In addition to the initial § 161.340 this study would be required selected the bacterial assay because it is battery, data from such mutagenicity on a case-by-case basis. Today the a primary test for detecting intrinsic tests must be submitted to the Agency, Agency is proposing to continue this mutagenicity of many classes of along with a reference list of all studies existing requirement by conditionally biologically active chemicals. The and papers known to the applicant requiring the study for all antimicrobial genetics of each test strain of concerning the mutagenicity of the test use patterns. The test note specifies that Salmonella and select strains of E. coli chemical. Having this information at the the study would be triggered if the have been well-validated, and the assay beginning of a mutagenicity assessment product’s use would result in exposure is easy to perform, is used routinely will greatly facilitate EPA’s effort to to domestic animals. throughout the world, and has an provide a more accurate assessment of R. Dermal Penetration extensive data base of tested chemicals. the mutagenicity of the antimicrobial The mammalian cells in culture assay pesticide in question. Currently in part 161 a dermal will detect a wider spectrum of possible penetration study is conditionally genetic endpoints not assayed in the O. Immunotoxicity required for all antimicrobial use bacterial test. The in vivo cytogenetics Just as with conventional pesticide patterns. Today the Agency is proposing assay provides an important chemicals, the Agency proposes to to continue this existing requirement by examination of the potential effect a test require immunotoxicity testing for all conditionally requiring a dermal compound may have on an intact antimicrobial pesticides. This would be penetration study for all antimicrobial mammalian system. Data from this a new data requirement. use patterns. study provide information on in vivo Immunotoxicity testing is necessary to IX. Handler and Post-Application metabolism, repair capabilities, evaluate the potential of a chemical to Exposure Data Requirements pharmacokinetic factors (e.g., biological produce adverse effects on the immune half-life, absorption, distribution, system. Immune system suppression has A. General excretion) and target organ/tissue been associated with increased Exposure data are used in the effects. incidences of infections and neoplasia evaluation of the exposures to persons EPA is proposing to modify the (abnormal and uncontrolled cell in occupational and non-occupational requirement for a bacterial reverse growth). In 1993, the National Research settings (§ 158.2260 and § 158.2270). For mutation assay conducted with Council reviewed the technical antimicrobials this includes residential, Salmonella typhimurium and literature and found that some commercial and industrial, institutional, Escherichia coli. For antimicrobials, it is pesticides are immunosuppressive (Ref. agricultural premises, and recreational not always practical to test 19). sites. Data include dermal, inhalation, antimicrobials for mutagenicity in Because the immune system is highly and non-dietary oral exposures. bacterial test systems such as the complex, studies not specifically Most past exposure research with bacterial reverse mutation assay. Most conducted to assess immunotoxic antimicrobial products has studied antimicrobial pesticides are toxic to function are inadequate to characterize either handler exposure (i.e., exposure bacteria, and therefore can only be a pesticide’s potential immunotoxicity, of people who mix, load, or apply tested at very low doses in bacterial even if some tissues subject to antimicrobial pesticides in the course of assays. This means that, for immunotoxic insult are examined. the application process or through other antimicrobials, negative results in While data from hematology, lymphoid work-related tasks) or post-application studies done in bacterial test systems do organ weights, and histopathology of exposure of people to residues of not necessarily demonstrate non- routine chronic or subchronic toxicity antimicrobial pesticides after mutagenicity. Given this limitation of studies may offer useful information on application, in treated areas or on bacterial reverse mutation assays such potential immunotoxic effects, these treated surfaces. as the Ames test, EPA must carefully endpoints alone are insufficient to Handler exposure research may review Ames studies conducted using predict effects on immunotoxic function measure exposure to undiluted antimicrobials. Cytotoxicity and the test (Refs. 15 and 16). Therefore, the Agency antimicrobial products as the products levels used in the study are critical is proposing to require functional are mixed for application, or it may factors to consider when determining if immunotoxicity testing along with the measure exposure to antimicrobial the results of an Ames test is acceptable data from immunotoxicity endpoints in products diluted for use. Antimicrobial or not, that is, whether the test fulfills other studies to predict the potential pesticide applicators may be industrial the data requirement. However, the risk of pesticides on the immune system or other workers, professional Agency has previously accepted Ames more accurately. applicators, or consumers using the tests for antimicrobials after review and product in or around their homes. P. Metabolism and Pharmacokinetics evaluation indicates the validity of the EPA considers handler exposure data results. If the results of the Ames tests Currently in part 161 a metabolism essential for fulfilling its mandate to are not valid, then the applicant would study is required for all food-uses and protect human health from pesticide need to discuss other mutagenicity conditionally required for all other use risk, including aggregate and cumulative testing with the Agency, such as a patterns. Today the Agency is proposing risk, and is therefore proposing to forward mutation assay conducted using to continue this existing requirement by require handler exposure studies for all mouse lymphoma L5178Y cells. The test requiring a metabolism and antimicrobial products, when the notes to the proposed mutagenicity pharmacokinetics study for high human toxicity and exposure criteria are

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00017 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59398 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

triggered. Codifying this requirement B. Use of Surrogate Data the label uses and use rates. would assist applicants for registration To support registration of an Consultation with the Agency is of antimicrobial pesticides to determine antimicrobial pesticide product, recommended for determining the which studies are required and then to according to the proposed tables in appropriate use site(s) for testing. design and conduct acceptable studies § 158.2260 and § 158.2270, applicants Studies of dermal exposure are often measuring handler exposure. would generate needed exposure data designed to concurrently measure Post-application exposure research with a typical end-use product. inhalation exposure. measures exposures of people to 2. Inhalation exposure studies. Just as However, the Agency recognizes the residues of antimicrobial pesticides after with the dermal exposure studies, EPA need to minimize the economic burden their use or application, and thus does proposes to require data for both of generating data to meet human not involve the direct exposure that outdoor and indoor inhalation exposure exposure data requirements while occurs during use. Of particular concern studies. In the absence of surrogate data, to EPA is the potential exposure of obtaining sufficient data and generally, the selection of the infants and children to post-application information for exposure and risk appropriate testing site(s) is based on residues of products used in and around assessments. Whenever appropriate, the exposure sites with the highest homes, daycare centers, or schools. surrogate data may be used for the potential for exposure. For inhalation The data requirements proposed here assessment of antimicrobial pesticides. exposure studies, the use sites with the are based on the Agency’s current The Agency is currently working with potential for the highest exposure are practice of requiring exposure data several industry Task Forces that are almost always indoors. Based on its when certain toxicity and exposure generating exposure monitoring data experience, the Agency believes criteria are met. These criteria are that may be able to be used as surrogate potential exposure is highest indoors described in proposed § 158.2260 and data sources. The Antimicrobial because the pesticide is confined in a § 158.2270. Today’s proposal seeks to Exposure Assessment Task Force closed area and therefore is less likely harmonize the exposure requirements (AEATF-II) is developing handler to be rapidly diffused or dispersed. This for antimicrobials with those of exposure data for antimicrobial means that if the application rates are conventional pesticides. The applicator applications (such as mopping, wiping, the same for an indoor scenario and an (handler) exposure data requirements aerosol sprays, painting, etc.). Task outdoor scenario, then the Agency may are the same as those codified for Force members can consider using this require only the indoor inhalation conventional pesticides. The post- surrogate data, if determined by the study, as that would have the highest application data requirements are the Agency to be suitable, to assess potential exposure. Consultation with same as conventionals, with the antimicrobial handler risk instead of the Agency is recommended for exception of one study (Dislodgeable generating their own data. If surrogate determining the appropriate use site(s) Foliar Residue and Turf Transferable data are inadequate for the Agency to for testing. Studies of inhalation Residues) that is not needed for adequately predict likely exposures and exposure are often designed to antimicrobials. the resultant risks, then applicants concurrently measure dermal exposure. The proposed requirement of such would need to submit chemical-specific 3. Biological monitoring. Biological data for antimicrobial products when and/or product-specific data. monitoring is the only type of applicator the toxicity and exposure criteria are C. Handler Exposure exposure study proposed as a triggered would allow the Agency to conditional requirement. Data from conduct more thorough exposure The Agency proposes to require data biological monitoring studies provide assessments for residential as well as addressing handler exposure for the Agency with estimates of the occupational sites, and to cover all use antimicrobials when the toxicity and internal dose or amount of a pesticide and exposure scenarios for such sites. exposure criteria are triggered. As in the body. EPA proposes to allow the EPA presented the need for additional discussed in Unit IX.A., this not only submission of biological monitoring handler exposure data to the SAP in codifies the Agency’s current practices, data in addition to, or in lieu of, dermal January 2007 (Ref. 39) and to the Human but also harmonizes the requirements or inhalation exposure data, provided Studies Review Board (HSRB) in April for antimicrobials with those of the human pharmacokinetics of the 2007 (Ref. 40). Both groups agreed that conventional pesticides. EPA now pesticide residue is sufficiently additional data are warranted. proposes to codify these requirements in understood to permit the back Research undertaken to address the proposed § 158.2260 and set out calculation to determine the total proposed handler and post-application explicitly in § 158.2260(b) the triggers internal dose, and providing further that data requirements may involve describing the circumstances under there are adequate analytical methods intentional exposure of human subjects which such data must be submitted. available. Biological monitoring offers as those terms are defined in EPA’s For handler exposure, the proposed the advantage of assessing the internal rules at 40 CFR 26.1102, and if they do, data requirements are as follows: dose, as opposed to the exposure or protocols and supporting 1. Dermal exposure studies. EPA amount of chemical coming in contact documentation as specified in that rule proposes to require data for both with the surface of the skin or available must be submitted for review by EPA outdoor and indoor dermal exposures to for inhalation in the lungs as measured and the HSRB before any subjects are estimate the dermal exposure to persons using passive dosimetry techniques. enrolled in the research. If research directly handling pesticides. The Because biological monitoring is involving intentional exposure of number of exposure studies that may be necessarily specific to the material human subjects is initiated without required depends on the variety of use tested, generally it cannot be conducted EPA’s prior review, the resulting data sites, their similarities, and whether the using a surrogate chemical. will not be accepted in support of uses are indoor or outdoor. In the 4. Data reporting and calculations. registration. Parties who are unsure absence of surrogate data, generally, the EPA proposes to require applicants to whether proposed research involves selection of the appropriate testing submit data reporting and calculation intentional exposure are encouraged to site(s) is based on the exposure sites information whenever applicator consult with EPA before proceeding with the highest potential for exposure. exposure data are submitted. These data with the research. Generally, this is determined based on are needed by Agency scientists for an

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00018 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59399

appropriate level of review and application product use information around and are in contact with treated evaluation, and offer a submission was presented to the FIFRA Science wood structures such as decks, play format that the Agency has found Advisory Panel (SAP) in March 1998. sets, and gazebos, and the surrounding useful. This information is important (The draft guideline is available at soils. This would be a new data because it allows EPA to assess the http://www.epa.gov/scipoly/sap/ requirement for antimicrobials. quality and validity of the exposure meetings/1998/march/contents.htm.) Protocols must be approved by the study and thus the accuracy of the The Agency will finalize both Agency prior to the initiation of the estimates and resultant exposure guidelines before publishing a final rule study. Details for developing protocols calculations derived from that study. establishing antimicrobial data are available from the Agency. The types of information that would be requirements. 2. Indoor surface residue dissipation. included under this data requirement The Agency proposes to require the D. Post-Application Exposure include: indoor surface residue dissipation study • The chemical formulas used in the The current data requirements for (sometimes known as a surface wipe calculations. post-application exposure in § 161.390 sampling study). This study supplies • The data used in the calculations, are focused on reentry to treated areas information on residue dissipation from including the raw data manipulation/ by agricultural workers. Since the treated areas and articles such as correction used in order to calculate promulgation of these requirements in carpets, hardwood floors, and counter limits of detection/limits of 1984, the Agency has become tops, after antimicrobial pesticides have quantification. increasingly concerned about post- been used. It is also used to determine • The statistical analyses required. application risks to persons in residue dissipation from decks and • The quality control data for lab/field occupational settings other than other structures manufactured from recovery and storage stability. conventional food, feed, and fiber crop treated wood. • The actual calculations. agriculture. The Agency is now These data would quantify residue Included within the data reporting proposing to require post-application loads and characterize the dissipation and calculations requirement would be exposure data for other settings where rate (i.e., how fast pesticide residues information on the ethical conduct of people may be exposed, regardless of disperse over time following the research. EPA regulations at 40 CFR whether they are on-the-job or application) of antimicrobial pesticides 26.1303 require that the ethical conduct bystanders. Under current practice, on indoor surfaces. The Agency could of all research involving human subjects post-application exposure data are then assess the magnitude and duration be fully documented at the time of generally required for occupational and of human exposure to antimicrobials submission of the data resulting from residential settings on a case-by-case present as surface residues. Without the research. This requirement will basis when specific toxicity and such data, the Agency has no precise apply to all exposure studies involving exposure criteria have been met. means of calculating human exposures human subjects submitted to EPA under Moreover, FFDCA mandates that EPA to such substances from contacting the pesticide laws, without regard to perform additional scientific analyses surfaces over time. This requirement whether the research involves which before 1996 had not been a would not apply to uses that are not intentional exposure. Data from routine part of the Agency’s risk surface treatments, e.g., aquatic areas, exposure studies not accompanied by assessment process, including the swimming pools, antifoulant coatings the required documentation of ethical assessment of aggregate exposures from and paints. conduct will not be accepted for review. multiple pathways including dietary The draft guideline for indoor surface 5. Product use information. EPA is and non-dietary routes of exposure. residue dissipation is available at http:// proposing to require product use The Agency proposes to require data www.epa.gov/scipoly/sap/meetings/ information for both occupational and addressing post-application exposure 1998/march/contents.htm. This draft residential use patterns. Product use for antimicrobials when the toxicity and guideline was externally peer-reviewed information assists EPA to more exposure criteria are triggered. Two new before presentation to the SAP in 1998. accurately assess pesticide exposure to exposure data requirements (soil residue An examination of the FIFRA SAP applicators by describing how the dissipation and non-dietary ingestion website since 1998 to the present will pesticide is actually used and applied. exposure) are today proposed for show many presentations to the SAP on EPA requires this information because antimicrobials. As discussed in Unit assessing occupational and residential differences in use can translate to IX.A., this not only codifies the exposures. Science has evolved in this significant differences in exposure, and Agency’s current practices, but also area. thus in risk. For applicator exposure, harmonizes the requirements for EPA notes that it has reviewed and use information may include, but is not antimicrobials with those of accepted many studies, on a case-by- limited to, who applies the conventional pesticides. EPA now case basis, that were not conducted in antimicrobial pesticide, the use sites, proposes to codify these requirements in accordance with current guidelines, but site locations, use directions, proposed § 158.2270 and set out which serve its needs and provide application rates and frequencies, explicitly in § 158.2270(b) the triggers suitable information for risk assessment application equipment and methods, describing the circumstances under purposes. The guidelines themselves do protective equipment used, protective which such data must be submitted. not impose mandatory requirements. clothing worn, and other information For post-application exposure, the Instead, they present recognized that will determine exposure to proposed data requirements are as standards for conducting acceptable antimicrobial pesticide handlers. follows: tests, guidance on evaluating and The Agency acknowledges that the 1. Soil residue dissipation. These data reporting data, definition of terms, and guideline for applicator product use are needed to characterize exposures to suggested study protocols. The draft information has not yet been finalized. residues of antimicrobials, and most guideline, therefore, serves as a starting However, the guideline for applicator particularly wood preservatives, that point for pre-protocol submission product use information should be occur through contact with outdoor meetings where the Agency’s scientists substantially similar to the one for post- soils. This information is critical for can provide guidance to registrants or application. The guideline for post- assessing risks to children who play task forces on aspects of study design.

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00019 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59400 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

The Agency’s scientists are always proposing to require a description of to antimicrobial pesticide residues must willing to work with individual human activities. Information on those only be an observational study, registrants to develop study designs to persons who may enter treated areas involving no intentional exposure of fulfill data requirements. The Agency after the application is complete has children. will finalize this guideline before been routinely submitted to EPA by Incidental oral exposure via hand-to- publishing a final rule establishing applicants and is now being codified as mouth, object-to-mouth and direct antimicrobial data requirements. a separate and distinct requirement mouthing/ingestion is an important For wood preservatives, EPA has These data will allow for a more exposure pathway for infants and worked with the Consumer Product accurate evaluation of the exposure toddlers. The results from these studies Safety Commission (CPSC) to develop potential associated with use of an will be used to assess the risks methodologies for conducting surface antimicrobial pesticide. The description associated with the incidental ingestion wipe sampling studies on wood. of human activity data would define the of antimicrobial pesticides by children Protocols for wood preservative treated activity patterns that affect exposures following antimicrobial pesticide surface wipe sampling studies must be (e.g., defining the exposed populations applications in residential or public approved by the Agency prior to the in commercial/institutional and settings, or exposure to treated surfaces initiation of the study. Details for residential settings, the application (e.g., carpets, toys, wood structures). developing protocols are available from sites, site-specific information on This study would be required for uses the Agency. exposure time per activity, type of in and around the home, daycare 3. Dermal exposure. EPA proposes to protective clothing worn, and any other centers and schools. require dermal exposure data for both relevant use activity data). The The Agency is primarily concerned outdoor and indoor dermal exposures to description of human activity with non-dietary exposures immediately estimate the dermal exposure to persons information would be used with the use following application of the exposed after the pesticide application information (both application and post- antimicrobial pesticide; therefore, has been completed. The discussion in application), to help the Agency dissipation studies alone would not Unit IX.C. of this preamble for handler determine whether the exposure provide the information needed to dermal studies is also applicable to potential for humans is likely to be assess risks from non-dietary ingestion. post-application exposures. significant, and if additional data will Information such as frequency/duration 4. Inhalation exposure. EPA proposes be needed. of hand-to-mouth activities and surface to require inhalation exposure data for 8. Data reporting and calculations. area mouthed are often needed as input both outdoor and indoor inhalation EPA proposes to require applicants to values for the calculations that are exposures to estimate the inhalation submit data reporting and calculation performed to assess non-dietary exposure to persons exposed after the information whenever post-application ingestion exposure. When appropriate, pesticide application has been exposure data are submitted. Such EPA’s Exposure Factors Handbooks (see completed. The discussion in Unit IX.C. information has been routinely http://cfpub.epa.gov/ncea/cfm/ of this preamble for handler inhalation submitted to EPA by applicants as part recordisplay.cfm?deid=20563) can be studies is also applicable to post- of any submission of exposure data and used as the source of this frequency/ application exposures. is now being codified as a separate and duration information. However, the data 5. Biological monitoring. A distinct requirement. The discussion in in these Handbooks cannot replace conditional requirement for biological Unit IX.C. of this preamble for handler chemical-specific information from monitoring data was discussed in Unit data reporting and calculations is also studies of treated articles/surfaces that IX.C. That discussion is also applicable applicable to post-application quantifies the amount of pesticide to the proposed conditional requirement exposures. Note in particular the residue on such surfaces. for biological monitoring for post- discussion of the requirement at 40 CFR Non-dietary ingestion may also occur application exposure which codifies the 26.1303 for full documentation of the through hand-to-mouth or object-to- Agency’s current practices. ethical conduct of all submitted mouth transfer of antimicrobial 6. Product use information. EPA research involving human subjects, pesticide residues during activities proposes to require product use whether or not they were intentionally performed by children (e.g., crawling) information for all antimicrobials. Such exposed. that put them in close proximity with information has been routinely 9. Non-dietary ingestion exposure. treated surfaces. Non-dietary ingestion submitted to EPA by applicants and is The Agency proposes to require a non- exposure would be expected in now being codified as a separate and dietary ingestion exposure study for residential or public (e.g., schools, distinct requirement. For post- residential types of exposures only. This daycare) settings following exposures to: application exposure, required product study is not required for occupational • Soils in contact with, or adjacent to, use information includes information on exposures since the primary concern for preservative-treated wood structures reapplication rates and frequencies, adult workers is exposure via the such as play structures. post-application entry restrictions, re- dermal and inhalation routes. This • Outdoor surfaces such as decks. entry intervals, rinsing and other would be a new data requirement that • Indoor surfaces such as residue removal practices, and other use evaluates the potential oral exposures to antimicrobial pesticide-treated paint data relevant to exposure after humans, particularly children, from chips, or antimicrobial-sprayed floors or application. The draft guideline for antimicrobial pesticide residues from walls. post-application product use sources other than food. • Antimicrobial-treated textiles, information is available at http:// Note that EPA regulations at 40 CFR polymers, or other items (e.g., clothing, www.epa.gov/scipoly/sap/meetings/ 26.1203 prohibits, without exception, bedding, carpets, or toys). 1998/march/contents.htm. The Agency conduct of any research intended for Non-dietary ingestion studies would, will finalize this guideline before submission to EPA under the pesticide for example, monitor the amounts of promulgating a final rule establishing laws which involves intentional pesticide residues in the rinsate from antimicrobial data requirements. exposure of children under 18. Thus, hand washing, and thus allow the 7. Description of human activity. For any study of potential exposure of Agency to develop science-based post-application exposure the Agency is children, oral or by any other pathway, models or formulas to estimate

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00020 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59401

inadvertent exposure. The draft The residue chemistry database is classified as either direct or indirect guideline for non-dietary ingestion is designed to determine the composition food uses, which are generally available at http://www.epa.gov/scipoly/ of the pesticide residue and how much delineated in Units X.B. and C. of this sap/meetings/1998/march/ of that residue is present in food or preamble. For the purposes of defining contents.htm. This draft guideline was animal feed. Residue chemistry studies the residue chemistry data requirements externally peer-reviewed before include those which define: for antimicrobials, the table in proposed presentation to the SAP in 1998. An • The nature of the residue, i.e., § 158.2290 further delineates direct and examination of the FIFRA SAP website metabolism studies. indirect uses into four categories: direct since 1998 to the present will show • The magnitude of the residue, i.e., and indirect food uses, agricultural many presentations to the SAP on those studies which measure how much premises, and aquatic uses. Applicants assessing occupational and residential of the residue of concern is present in should consult with the Agency on the exposures. Science has evolved in this food, feed, and water. appropriate category(ies) for their area. Food-use pesticides require both product. EPA notes that it has reviewed and types of studies. Both plant and accepted many studies, on a case-by- livestock metabolism studies are needed B. Direct Food Uses case basis, that were not conducted in to determine the breakdown of the If the antimicrobial is applied directly accordance with current guidelines, but pesticide chemical in a living system, to food or water, it is a direct food use. which serve its needs and provide that is, whether the chemical stays Such uses would include, but are not suitable information for risk assessment intact or is converted into metabolites. limited to: purposes. The guidelines themselves do Occasionally, the metabolites are toxic • Livestock. not impose mandatory requirements. and are included in the analyses as a • Livestock feed. • Instead, they present recognized residue of concern. Magnitude of the Drinking water for humans, livestock residue (MOR) studies are performed to and/or poultry. standards for conducting acceptable • tests, guidance on evaluating and determine the level of residues of Egg washes. concern in food. Data collection residue • Fruit and vegetable rinses. reporting data, definition of terms, and • suggested study protocols. The draft analytical methods are reviewed by EPA Aquatic areas that have the potential guideline, therefore, serves as a starting as part of the validation of the to contaminate potable water. • Post-harvest applications that occur point for pre-protocol submission metabolism and MOR studies which are in the field, at a treatment facility (such meetings where the Agency’s scientists used to establish tolerances. In addition to dietary risk as a packing shed), during transport, can provide guidance to registrants or assessments, residue chemistry data are and while in storage, until the task forces on aspects of study design. used to establish pesticide tolerances, processing of the raw agricultural The Agency’s scientists are always the maximum level of pesticide residue commodity begins. willing to work with individual that may remain on food. Because these No currently registered antimicrobial registrants to develop study designs to are legal limits enforced by FDA, products are applied to agricultural field fulfill data requirements. The Agency enforcement methods for detecting the crops. Should an application for such an will finalize this guideline before presence and amount of the residue are antimicrobial product be submitted to publishing a final rule establishing needed, and are used by FDA, USDA, EPA, then the Agency would likely antimicrobial data requirements. and the States for food inspection require the same data as specified in X. Residue Chemistry Data purposes. part 158, subpart O for other field-use Requirements There are distinct differences between pesticides applied to crops, as the test the residue chemistry requirements of notes more accurately reflect the A. General conventional pesticides that are applied conditionalities of a terrestrial use EPA proposes to adapt the basic to crops in a field setting and those of pattern. residue chemistry data requirements antimicrobials that are more likely to be (§ 158.2290) as listed in subpart O of applied in a confined setting such as a C. Indirect Food Uses current part 158 to support applications food processing plant. Those differences For the purpose of determining for antimicrobial products. However, are reflected in the data requirements. residue chemistry data requirements, an EPA also proposes to modify the For example, no migration studies are antimicrobial use is considered an applicability of those requirements to required for terrestrial food and feed indirect food use when the reflect the differing risks and levels of uses in part 158, subpart O, and no antimicrobial pesticide is applied to a exposure of antimicrobials. Residue rotational crop studies are required for surface or incorporated into a material chemistry data are used by the Agency any antimicrobial uses. Certain test that will subsequently contact food, that to estimate dietary exposure to pesticide notes in part 158, subpart O and in is, the pesticide is not applied directly residues from food. If there are no direct subpart W are also different. As to the food. Residues of the pesticide or or indirect food uses for the expected, the differences result from the its degradates can be transferred to the antimicrobial, then no residue different use patterns. food when it comes into contact with chemistry data are required. Units X.B. and C. of this preamble these treated surfaces and articles. The proposed changes will allow EPA discuss the two main categories of food- Antimicrobial products labeled for to better estimate human dietary uses for the purpose of antimicrobial treatment of hard non-porous surfaces exposure to antimicrobial residues in or residue chemistry data requirements, which may come into contact with food on food or feed, to more accurately direct and indirect. Units X.D. through (e.g., food area premises and equipment) assess tolerances and tolerance Q. of this preamble explain changes to are classified as indirect food contact exemptions, and to provide additional specific residue chemistry data uses. Sanitizers and disinfectants which tools for the enforcement of pesticide requirements appropriate to remain on the surface of food-handling residue tolerances to ensure that food antimicrobials. For the purpose of or processing equipment are indirect entering the commercial market meets determining antimicrobial residue food uses. Sanitizers incorporated into the ‘‘reasonable certainty of no harm’’ chemistry data requirements, most articles (e.g., plastic products such as standard under FFDCA. antimicrobial pesticides will be coffee cups or cutting boards) intended

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00021 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59402 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

for food contact are also indirect food evaluate the need for a tolerance or proposing to continue to conditionally uses. tolerance exemption by assuming require a nature of the residue in Hard surfaces are considered to be complete transference of the chemical livestock study to support direct food food surfaces when food is prepared for into food over the lifetime of the treated contact uses and aquatic areas. As with consumption, either commercially or product. Alternatively, the applicant the data requirements for conventional residentially on such surfaces. Examples may submit migration studies to pesticide chemicals EPA is proposing to of hard surfaces are eating utensils, demonstrate the rate or amount of change the chemical substance with dinnerware, pots and pans, cutting transference of the antimicrobial into which the test is performed. This would boards, food preparation surfaces, food items. codify existing practices. countertops, refrigerator shelves, For antimicrobials used to treat refrigerator bins, ice trays, dining table D. Chemical Identity animal drinking water, or to treat wood tops, and cabinet shelves. Wood treated Currently in part 161, information on in contact with animals or animal feed, with an antimicrobial pesticide product chemical identity is required for all use or in aquatic areas, the Agency proposes could be used to construct or maintain patterns. Today the Agency is proposing to change the test substance for the a bee hive, a cattle trough or feeding to continue this existing requirement by nature of the residue in livestock study station. These and other indirect requiring information on chemical from ‘‘pure active ingredient, contacts with food or feed are assessed identity for all antimicrobial use radiolabeled (PAIRA) and plant to evaluate the need for a tolerance or patterns. metabolites’’ to ‘‘PAIRA or radiolabeled tolerance exemption. plant metabolite.’’ The test substance For the purpose of conducting a risk E. Directions for Use ‘‘metabolites’’ will be changed to assessment for a sanitizer (an Currently in part 161, directions for ‘‘metabolite’’ to clarify that dosing with antimicrobial not rinsed from food- use are required for all use patterns. more than one compound in any one contact surfaces), the Agency uses the Today the Agency is proposing to study is not acceptable. This is needed directions on the antimicrobial product continue this existing requirement by because in studies involving label in combination with modeled data requiring this information for all simultaneous dosing with both the to determine the amount of the sanitizer antimicrobial use patterns. active ingredient and plant metabolites, remaining. Under this approach, EPA it is impossible to determine the amount will initially assume that all of the F. Proposed Tolerance of metabolite due to active metabolism sanitizer residues remain on the surface Currently in part 161, a proposed from that introduced through and thus have the potential to enter the tolerance is required for all food-use intentional dosing. Simultaneous dosing food. This is a worst-case or screening- patterns. Today the Agency is proposing with the active ingredient and any level assumption. EPA will then use this to continue this existing requirement by metabolites may not produce useful modeled estimate in combination with requiring a proposed tolerance for all results, because the active ingredient toxicity data to determine if there is a antimicrobial food-use patterns. and metabolites may have different risk of concern and/or whether to metabolic pathways that cannot be establish a tolerance or tolerance G. Reasonable Grounds in Support of differentiated. In most cases dosing with exemption. If there are risk concerns Petition only the parent compound is necessary. and if scientifically appropriate, EPA Currently in part 161, reasonable However, in cases where plant and may refine the estimate of residues grounds in support of petition is animal metabolites are found to differ, remaining on the surface using more required for all food-use patterns. Today separate studies in which livestock are realistic model assumptions. If no risks the Agency is proposing to continue this dosed separately with each unique plant of concern are identified using these existing requirement by requiring this metabolite may also be required. refined assumptions, then most likely information for all antimicrobial food- The Agency proposes to specify in the EPA would not require higher-tiered, use patterns. test note that the livestock metabolism measured surface residue data. Of study would be required when an course, as an alternative to the Agency’s H. Submittal of Analytical Reference antimicrobial is applied directly to use of these screening-level or refined, Standards livestock, to livestock premises, to modeled estimates, the applicant may Currently in part 161, submittal of livestock drinking water, to livestock provide data that measures the actual analytical reference standards is feed, or to crops used for livestock feed. amount of sanitizer remaining on the required for all food-use patterns. Today This would also include antimicrobial treated surface or transferring to food. the Agency is proposing to continue this uses to treat wood in contact with For disinfectants (antimicrobials with existing requirement by requiring animals or animal feed, or in aquatic potable water rinses) EPA proposes to submittal of these standards for all areas given the potential use for crop generally follow the risk assessment antimicrobial food-use patterns. and livestock production. Such approach outlined for sanitizer I. Nature of the Residue in Plants applications may result in both oral and solutions. EPA would disregard the dermal exposure of animals to the potable water rinsing and assume that The Agency proposes to continue to pesticide and, depending on the results, worst-case residues (estimated using the require a nature of the residue study in may necessitate magnitude of the sanitizer model) are available for plants for aquatic uses and direct food residue studies to quantify the residues entering food items. Alternatively, the contact uses. The Agency proposes to in meat, milk, poultry, and eggs. applicant can provide data measuring continue to conditionally require this the actual amount of disinfectant study to support agricultural premise K. Residue Analytical Methods remaining on the surface or transferring uses. EPA proposes to require development to food after rinsing the treated surface. and submission of analytical methods J. Nature of the Residue in Livestock If the antimicrobial is to be whenever a numerical tolerance is incorporated into products with food The Agency proposes to continue to established. Residue analytical methods contact uses and bears a claim of surface require a nature of the residue in have two primary purposes: sanitizing activity, the Agency will livestock study to support agricultural • To collect residue data for generally, in the absence of data, premise uses. The Agency is also establishing tolerance levels and

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00022 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59403

conducting dietary exposure As with the data requirements for possible, it is clearer to list these as two assessments. conventional pesticide chemicals, the separate data requirements. • To enforce the tolerances established Agency proposes to change the chemical M. Storage Stability by EPA in 40 CFR part 180. substance for residue analytical Residue analytical methods are methods from ‘‘TGAI and metabolites’’ As with conventional pesticides, the currently required in part 161, and EPA to ‘‘residue of concern.’’ This would Agency proposes to add a storage proposes to continue this requirement. codify existing test practices. stability study as an explicit These methods are required only if a As with conventional pesticide requirement to validate the results of the numerical tolerance is established and chemicals (subpart O of part 158), the various magnitude of the residue since numerical tolerances are rarely Agency is proposing to require an studies. Such data have been required established for antimicrobials, independent laboratory validation (ILV) previously as a part of the magnitude of submission of this data should be a rare of residue analytical methods to ensure the residue study, but will now, as with occurrence. the accuracy and reproducibility of data conventional pesticides, be codified as a In part 158, subpart W, EPA is used for tolerance enforcement separate requirement. As discussed in a proposing to create separate entries in purposes. Codifying this current (since test note to the proposed table in the proposed table in § 158.2290 for 1988) practice (Ref. 28) would promote § 158.2290 storage stability data are these two types of residue analytical development of clearly written, required for any food or feed use methods to clearly indicate the need for complete descriptions of analytical requiring magnitude of the residue both types of methods, or a method that methods that can be used by Federal studies unless analytical samples are can be used for both data collection and and State enforcement agencies. stored frozen for 30 days or less, and the active ingredient is not know to be enforcement purposes. EPA believes L. Multiresidue Method Testing that the separation of the combined volatile or labile. This test note would requirement into separate and distinct The current requirement in 40 CFR clarify when storage stability data are requirements will provide clarity to part 161 for residue analytical methods needed and also harmonizes the applicants. actually encompasses several requirements for antimicrobials with The enforcement method has the submissions to the Agency. The first is those of conventional pesticides. following characteristics: the chemical-specific method(s) Magnitude of the residue studies • Analyzes for the residues of discussed in Unit X.K. of this preamble address how levels of pesticide residues regulatory concern, i.e., those named in and the second is the multiresidue in samples of human foods and the established tolerance. testing. In promulgating its part 158 livestock feeds are determined. These • Is reasonably rapid (typically one conventional pesticide data samples are often stored for extended day or less). requirements, the Agency separated this periods of time prior to analysis. Since • Uses readily available equipment combined requirement into separate and tolerances are based on residues at the and reagents. distinct requirements. EPA is proposing time of harvest (or sample collection) • Must be clearly and completely to do the same for antimicrobial and the residues may be lost by described in a stepwise manner such pesticides. processes such as degradation and that laboratory personnel competent Today, the Agency is proposing to volatilization during storage prior to using similar procedures can codify the requirement for testing the analysis, storage stability data successfully perform the procedure on residue of concern of the antimicrobial predicting the pattern of degradation, if the first trial. pesticide using the FDA’s and the any, of residues during this period are • Is subject to an independent USDA’s multiresidue methods (MRM) critical to understanding the results of laboratory validation. as a separate data requirement. As the field trial studies. • Has a mechanism to confirm the above, the Rs and CRs in the proposed N. Magnitude of Residue (MOR) Studies results. table in § 158.2290 reflect the Agency’s The data collection method has the best professional estimate of the As with conventional pesticides, the following characteristics: likelihood of a numerical tolerance Agency proposes to change the test • Analyzes for all residues of being established. This testing is substance from EP (end-use product) to toxicological concern. required only if a numerical tolerance is TEP (typical end-use product) for the • No limitation on duration of established and since numerical following types of MOR studies: Crop procedure. tolerances are rarely established for field trials, processed food or feed, • May use specially-developed and antimicrobials, submission of this data potable water, fish, irrigated crops, and very expensive equipment. should be a rare occurrence. food handling studies. • Validation is subject only to internal MRMs are important components of Residue data are needed for only one laboratory controls. pesticide monitoring and enforcement TEP of each formulation type used on a If the applicant can develop one programs. In food monitoring programs, given commodity or site. When newer method and the Agency finds that this such as those of FDA and USDA, it is or other types of formulations are one method satisfies the criteria for both not practical or feasible to test for each proposed for use, either additional the enforcement and the data collection individual pesticide in a separate test. residue data can be submitted to show method, then only one method needs to The MRMs are used to detect the that the use of these new or different be submitted. Otherwise, two methods presence of many pesticides, and then if formulations result in residues must be submitted. For the proposed needed, re-testing is done with the comparable to those arising from the table in § 158.2290 the ‘‘Rs’’ and ‘‘CRs’’ chemical-specific tolerance enforcement original formulation for which residue specified in the residue analytical method. Since the residue analytical chemistry data already exist, or side-by- method data requirements reflect the method requirement is intended to refer side bridging studies can be conducted Agency’s best professional estimate of to a method that is specific for one for the different types of formulations. If the likelihood of a numerical tolerance pesticide (sometimes called a ‘‘single the new formulation results in residues being established for an antimicrobial residue method’’) and the multiresidue higher than those from use of the pesticide chemical and thus resulting in methods currently in use are designed original formulation, then the same the requirement to submit the data. to measure as many pesticides as number of trials would generally be

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00023 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59404 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

required for the new formulation as was most common studies applicable to AR data would be required when required for the original formulation. antimicrobials. estimates of risk have been refined using This would codify a longstanding information and any measured data P. Anticipated Residues practice at EPA for various MOR initially available to EPA, and these studies. The Rs and CRs reflect the The term ‘‘anticipated residue’’ (AR) refined risks result in a risk of concern. likelihood of the need for MOR studies refers to exposure data that would Taking samples from treated hard in the Agency’s best professional permit significant refinement of dietary surfaces is an example of one source of judgment. Test notes to the table in the exposure estimates. Refinement means residue data that could be used to proposed § 158.2290 describe the that the Agency would estimate very generate more realistic dietary exposure specific circumstances in which MOR realistic dietary exposure estimates after estimates for an indirect food-use. studies may be required for an first using the screening-level estimates If there is no food-use, then AR data antimicrobial. that allow EPA to perform a very quick, would not be submitted to EPA. AR data but conservative dietary risk O. Magnitude of Residue in Meat, Milk, would be a conditional requirement that assessment. is triggered only when estimates of risk Poultry, and Eggs As previously discussed, no currently conducted using residues at the registered antimicrobial products are Similar to the livestock metabolism tolerance level may result in a risk of applied to agricultural field crops. study, the Agency proposes to change concern. This means that AR data Generally, for antimicrobial direct food- the test substance for the meat/milk/ would be required only for a food-use, uses, when performing the initial, poultry/egg (M/M/P/E) MOR studies. and only if a numerical tolerance is screening-level dietary risk assessment, Due to the difficulties in interpreting established, and then only if the risk EPA uses the antimicrobial tolerances as results of studies in which a mixture is assessment conducted at tolerance level the input values for dietary modeling. If fed, the Agency is currently results in a risk of concern. This would there are risk concerns and if discouraging the feeding of mixtures be an infrequent occurrence for scientifically appropriate, EPA may and is instead requesting the feeding of refine (that is to be more realistic) the antimicrobials. Establishing this data isolated compounds in livestock input values by using data showing the requirement for antimicrobials not only studies. Hence, to codify current pesticide residues in food closer to the codifies the Agency’s current practices, practice, the test substance will be point of consumption. Market basket but also harmonizes the requirements changed to read a single plant surveys are an example of one source of for antimicrobials with those of metabolite instead of metabolites in the residue data that could be used to conventional pesticides. plural. Provided that plant and animal generate more realistic dietary exposure Q. Food Migration Studies metabolites are the same, the parent estimates for direct food-uses. compound must be the test substance in Anticipated residue data would be This study is unique to antimicrobials livestock feeding studies. If any plant required when estimates of risk using and this proposal codifies current metabolite exists that is not also an residues at the tolerance level result in practices. EPA is proposing to animal metabolite, a separate feeding a risk of concern, and a more realistic conditionally require a migration study study may be required involving dosing estimate is needed. for indirect food uses when modeled with that unique plant metabolite. The However, antimicrobials also include estimates of the amount of antimicrobial Agency will inform the applicant when indirect food uses such as sanitizers and residues transferred to the food or feed this additional testing is required. It is disinfectants which remain on the may result in a risk of concern. This expected that this study will be rarely surface of food-handling or processing study would not be required for any requested. equipment. For these indirect food-uses, other uses. The Agency proposes to continue the generally when performing the initial, A migration study is performed to conditional requirement for M/M/P/E screening-level dietary risk assessment, determine the amount of a chemical MOR studies for agricultural premises, EPA uses several high-end (over- substance that can enter a food indirect food uses, direct food uses and estimated) assumptions as the input commodity through contact with a aquatic uses. There are three types of M/ values for dietary modeling. In such an treated surface. There are two basic M/P/E MOR studies: livestock feeding assessment, the same assumptions are types of migration studies. The first type studies, direct livestock treatments, and used for every dietary assessment. Such includes sanitizing and disinfecting agricultural premise treatments. The an assessment can be performed solutions that are applied to equipment Agency proposes to clarify that livestock quickly, and if there are no risk in a food-processing facility. The second feeding studies generally are not concerns, then the dietary assessment is type includes matrices such as wood, required when (1) residues are not considered to be complete. However, if plastic, paper, cloth, or rubber which found in/on feed items or (2) livestock there are risk concerns and as may be impregnated with antimicrobial metabolism studies indicate minimal scientifically appropriate, EPA would pesticides. The migration of the transfer of the pesticide residue to begin a process of using the available antimicrobial into the food occurs when tissues, milk or eggs. For those information and data to refine, that is to the food commodity comes into contact pesticides which leave non-detectable be more realistic, in estimating input with the treated surface or the or low residues in feed items and for values. impregnated matrix. which the livestock metabolism study Since the screening-level risk As previously discussed, the Agency shows little transfer of radioactivity to assessment did not consider the believes that it is possible to model a tissues, the Agency may be able to particular use pattern of the worst-case estimate of the amount of the conclude that data on the level of antimicrobial chemical, as a first antimicrobial chemical that migrates residues in livestock and their refinement, EPA would modify the into the food commodity. If the worst- byproducts are not necessary. Livestock assumptions to account for the case estimates do not result in a risk of premise treatment studies are required particular use pattern of the chemical. concern, then the applicant would not for those antimicrobials used to clean or Refinements to the assumptions can also need to submit a migration study. As an otherwise treat livestock premises such be made if measured data such as a alternative to these worst-case estimates, as feedlots. These are expected to be the migration study were available. the applicant may provide data for the

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00024 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59405

amount of sanitizer/disinfectant high environmental exposure grouping • Commercial, institutional and remaining on the surface. as discussed in Unit XI.B. industrial premises and equipment. There is no Agency guideline for • Residential and public access B. Determination of the Two Groupings: conducting a migration study. EPA premises. Low and High Environmental Exposure routinely accepts studies performed • Medical premises and equipment. according to FDA’s food migration 1. Factors considered in determining • Human drinking water systems. protocol/guidance. Applicants are the groupings. As previously discussed, • Materials preservatives. encouraged to use existing FDA EPA is proposing to establish its 12 • Swimming pools. methodologies. Information that could antimicrobial use patterns in § 158.2201. • Recirculating industrial processes be of value to applicants developing EPA examined these use patterns and and water systems (part of the industrial protocols is on the FDA website (Refs. identified those that occur outdoors, processes and water systems use 7, 9, 10, and 11). Protocols must be discharge effluent directly to the pattern). approved by the Agency prior to the outdoors, or result in materials treated initiation of the study. However, if a with antimicrobials (i.e., wood C. Data Requirements for Wood migration study has been reviewed and preservatives and antifoulants) being Preservatives accepted by FDA, then this fact should placed in the environment. Given this As discussed previously in this be included in the submission to EPA, direct link to the environment, and proposal, wood preservatives are along with the migration study. correspondingly higher exposure considered to be an antimicrobial use potential, there is a greater potential for XI. Environmental Risk Assessment pattern with high expectation of concern. In fact, EPA has been requiring environmental exposure. Wood that has A. General more data for such use patterns than for been treated with a wood preservative other antimicrobial use patterns. Environmental fate studies evaluate product is placed directly into the 2. The high environmental exposure outdoor environment, thus leading to the mobility, distribution and grouping. The Agency believes that the dissipation of a pesticide in various the potential for significant release of potential for environmental exposure is the wood preservative into the compartments of the environment, such high for three of the use patterns and as water, soil, air, and sediment. These environment. The data required to part of a fourth use pattern. For the register a wood preservative product studies are designed to identify which purposes of requiring data, the dissipation processes are likely to occur depend on the use site of the treated following use patterns represent the wood, which can be land-only, aquatic- when the pesticide is released into the high environmental exposure grouping environment and characterize the only or both. For instance, a wood for environmental fate (§ 158.2280) and preservative product which would be significant degradates likely to result ecotoxicity (§ 158.2240 and § 158.2250) from these processes. Data from these used in or near water will usually have data requirements: more data requirements concerning the studies are used as inputs in exposure • Once-through industrial processes effects of the pesticide on aquatic models, and, in conjunction with and water systems (part of the industrial organisms than a product that is not ecological effects studies, are used to processes and water systems use used in or near water. assess whether a pesticide has the pattern). potential to cause adverse effects to • Antifoulant paints and coatings. Therefore, if a product specifies that wildlife, fish, plants, and humans. • Wood preservatives. wood that has been treated with that Environmental fate studies are • Aquatic areas. product cannot be used in areas with discussed in Unit XII. of this preamble. The data that have been typically the potential for that wood coming into Ecological effects data are used by the required for the use patterns now contact with water, then EPA believes Agency to determine the toxicological included in the high environmental that the potential for exposure is hazards of pesticides to various exposure grouping are used to calculate decreased. Accordingly, it is current nontarget organisms, such as birds, estimated environmental concentrations EPA practice to require fewer mammals, fish, bees, terrestrial and (EECs) of the pesticide in different environmental fate and ecological aquatic invertebrates, and plants. These environmental media. These EECs are effects studies for such products. In tests include short-term acute, subacute, needed to conduct quantitative practice it is difficult to assure that reproduction, simulated field, and full environmental and ecological risk wood treated with a wood preservative field studies arranged in a tiered system assessments. These data would also that is for land-use only will not come that progresses from the basic laboratory have applicability to drinking water in contact with water. Treated wood tests to the applied field tests. exposure assessments that are used in intended for a use with little potential Ecological effects testing for nontarget human health risk assessments. aquatic exposure could be inadvertently organisms are discussed in Unit XIII, 3. The low environmental exposure diverted to other uses, such as marine and nontarget plants in Unit XIV of this grouping. The low environmental docks or pilings, which would have preamble. exposure grouping is defined as those considerable aquatic exposure. The These data provide a foundation for use patterns that are not included in the Agency does not know if or how often an environmental risk assessment. The high environmental exposure grouping. this kind of diversion occurs. However, results of the environmental fate For the purposes of requiring data, the the Agency notes that in the United assessment are evaluated in conjunction following use patterns represent the low States, wood preservatives are with the results of the ecological effects environmental exposure grouping for categorized using the American Wood data to determine the potential of the environmental fate (§ 158.2280) and Preservers’ Association Use Category pesticide to cause harmful effects to ecotoxicity (§ 158.2240 and § 158.2250) system. These categories describe the nontarget organisms and plants. data requirements: exposure conditions which treated The Agency has divided the • Agricultural premises and wood products can be subjected to antimicrobial pesticides into two groups equipment. when in service. The categories, for determining environmental fate and • Food-handling and storage although general, provide some measure ecotoxicity data requirements: the low establishments, premises and of control over how treated wood environmental exposure grouping and equipment. products are used.

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00025 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59406 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

A concern that has been raised to EPA ecological effects data will be needed to to the SAP, this was ‘‘to ensure the is the difference in how different support registration. safety of environmental discharge but countries regulate wood preservative Once the higher-tiered studies have also for protection of publicly owned products. This could present a challenge been reviewed and evaluated, then the treatment works (POTWs) and other for joint reviews of wood preservatives Agency would use all these data to treatment systems which often rely on since different data requirements and develop quantitative environmental fate microbial treatment processes.’’ In differing programmatic objectives could and drinking water exposure response to the SAP’s concerns, the result in different regulatory decisions. assessments, and to calculate estimated Agency reexamined the need for Today’s proposed data requirements environmental concentrations of the environmental fate data other than are based on EPA’s current practice of pesticide in different media (such as hydrolysis. As a result of this 1997 determining the data required for a water, sediment, or soils) under various reexamination, the Agency determined pesticide application and site scenarios. wood preservative product dependent to conditionally require data on The Agency uses these estimates of on the usage (land-only versus land and photodegradation in water for low exposure in conjunction with toxicity aquatic). The Agency requests environmental exposures. At that time, data to assess whether a pesticide has comments on the regulation of wood the Agency determined not to require the potential to cause adverse effects on preservative products, and based on the biodegradation or microbial data. human health via exposure through More recently, as part of its comments received could continue with drinking water and the environment via development of this proposed rule, EPA the split usage or determine to no longer exposures through both water and soil. re-evaluated the 1997 SAP have such a split usage. recommendations concerning the data B. History of Environmental Fate Data requirements for environmental fate, XII. Environmental Fate Data Requirements for Antimicrobials Requirements and nontarget plant and organisms. The In 1984, at the time of promulgation reason for this re-evaluation was, in A. Environmental Fate Data of the original part 158 data part, due to certain comments that were Requirements for Antimicrobials requirements, there were no received in response to the 2005 The Agency proposes to adapt the environmental fate data requirements proposed rule for conventional pesticide basic environmental fate data types for the indoor use pattern. At that time, chemicals (70 FR 12276, March 11, EPA assumed that many of the indoor (§ 158.2280) as listed in subpart N of 2005). Additionally, the Agency was uses went down-the-drain to a current part 158 to support applications also becoming increasingly aware of wastewater treatment plant (WWTP), at for antimicrobial products. EPA also detections of antimicrobial chemicals in which point dilution and degradation, proposes to modify the applicability of various environmental compartments. or removal by WWTP processes would those requirements to antimicrobials to The Agency received comments from mitigate environmental concerns. Thus, reflect differing risks and levels of four California water treatment currently, in part 161, there are no exposure. Moreover, new types of data authorities and from environmental environmental fate data requirements are needed to evaluate the risks agencies from two cities in California. for the indoor use pattern. The comments centered on their strong associated with use patterns more In 1997, the Agency presented a draft typically associated with antimicrobials, recommendations that FIFRA data of the antimicrobial data requirements requirements should be equivalent to such as discharge through sewer to the FIFRA Science Advisory Panel the data required to develop water systems and wastewater treatment (SAP) (Ref. 29). As part of its quality criteria (WQC) under the Clean plants to the environment. As discussed presentation EPA explained its intent to Water Act (CWA) and should consider in this Unit, such studies could include: divide antimicrobial uses into two water quality issues related to urban Activated sludge sorption isotherm, groupings based on the potential for pesticide use. California water-treatment ready biodegradability, and modified environmental exposure (high authorities questioned the adequacy of activated sludge, respiration inhibition environmental exposure and low the Agency’s assessment of risks with test. environmental exposure). In 1997, the regard to water quality considerations Fate studies characterize how a Agency defined the low environmental including: Use of aquatic toxicity data, pesticide chemical dissipates once it is exposure grouping as the following surface water quality studies, and urban released into the environment, and eight use scenarios: Agricultural uses of pesticides, particularly when identify the significant transformation premises and equipment; food- these uses result in pesticide residues in products likely to result from these handling/storage establishments receiving waters from storm sewers or processes. Fate studies include both premises and equipment; commercial, sewage treatment plants. laboratory and field studies. Such institutional and industrial premises EPA believes that even though these studies can provide input parameters and equipment; residential and public comments were received in response to needed in simulation modeling. Under access premises; medical premises and the conventional pesticide chemicals a tiered testing scheme, a specified set equipment; human drinking water proposed rule, the submitted of laboratory studies determined by the systems; materials preservatives; and information on receiving waters for use patterns is performed first, and then swimming pools. For these eight use wastewater treatment plants is a preliminary, qualitative environmental scenarios for environmental fate data particularly applicable to fate and transport assessment is the Agency intended to require a very antimicrobials, many of which are used developed from the results of those reduced data set (hydrolysis data). indoors. This means that the lower-tiered studies and the modeling. In its report, the SAP expressed its antimicrobial goes down-the-drain and This assessment could determine that concerns about ‘‘the lack of chemical eventually reaches a wastewater no additional studies are needed. Or, fate data,’’ indicated that hydrolysis treatment plant. Therefore, in its this assessment could trigger higher- would be an important pathway of response to comments document for the tiered laboratory-based studies, and/or concern for only a subset of final rule for conventional pesticide to design or trigger appropriate field antimicrobial chemicals, and stated that chemicals, EPA agreed that pesticide studies. Fate studies can also be used as both biodegradation data, and microbial discharge into municipal sewage triggers for determining which data should also be required. According systems is an important issue

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00026 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59407

particularly for those antimicrobial the environment, or result in materials studies that would be triggered are pesticides which are typically rinsed treated with antimicrobials being placed based on a weight-of-evidence down the drain. EPA stated it would in the environment. Since these use evaluation of the results of the lower- consider the issue of down-the-drain patterns are unlikely to go down-the- tiered studies are discussed in Units chemicals in the proposed rule for drain, a screening-level environmental XII.L. – Q. EPA’s proposal to antimicrobials. fate assessment is not needed. conditionally require these data for the As a first step toward re-evaluating its low environmental exposure grouping C. Today’s Proposal for Low processes and procedures for would for these studies expand the Environmental Exposure Antimicrobials conducting a risk assessment for an number of use patterns for which the antimicrobial chemical that goes down- The Agency believes that test is conditionally required. the-drain, the Pesticide Program environmental exposures from the use It may be possible to model some of discussed these issues with EPA’s Office patterns discussed in Unit XI.B.3. of this the needed parameters. The applicant is of Water (OW). The Agency is becoming preamble are likely to be small, because encouraged to review the approach increasingly aware of detections of (1) the sites where these uses occur are discussed in Unit XVIII.A. of this antimicrobial pesticide chemicals in not rapidly or directly connected to preamble on the use of Structure- various environmental compartments, aquatic environments, (2) some of the Activity-Relationship (SAR) including surface water. An example of applications occur on a very infrequent assessments to ascertain if such a chemical with such detections is basis and other applications involve techniques could provide useful triclosan (Refs. 12, 17, 22, and 23). The very small amounts of the antimicrobial, information in preparing their detection of such chemicals in surface and (3) in many cases wastewaters submission to EPA. water indicates that the antimicrobial containing these antimicrobials are EPA is proposing to conduct the (or its degradate) is moving from the processed in WWTPs. The indirect screening-level of its fate assessment for area of application, down-the-drain to a movement of antimicrobials from the these low environmental exposure WWTP, and then into the environment use sites into the outdoor environment antimicrobials with non-direct, delayed via the treated effluent. Certain occurs mostly through water. In many environmental connections in a three- chemicals can pose a risk even at low cases, leachates, rinsates, and flushes pronged approach. The three prongs are levels. Based on the Agency’s concerns are released down-the-drain, and designed to (1) estimate the number of about the potential effects of eventually reach a WWTP. WWTPs days per year of exceedance of the antimicrobials on the biological degrade chemicals in their influent, antimicrobial surface water treatment processes used in WWTPs, although the degree of degradation concentration of concern to aquatic concerns about potential varies widely depending on the organisms in a surface water body bioconcentration of antimicrobials after chemical, the treatment process and downstream of a treatment plant, (2) release, and possible effects on other factors (e.g., ambient temperature). determine any negative effect of the nontarget species, the Agency now After treatment, the effluent (the treated antimicrobials in the influent on the believes that new environmental fate water and any chemicals remaining in activated sludge biomass in biological data requirements are needed for down- that water) is released into the aquatic wastewater treatment systems, and (3) the-drain antimicrobial uses. environment, or to the terrestrial determine the potential for the Therefore, EPA is proposing to require environment via land application of antimicrobial to accumulate in sediment data to address environmental fate sewage sludge. or in organisms downstream from the (degradation), biodegradation data, and Given the expectation of low WWTP release, or for there to be microbial data, for the low exposures to the environment, EPA negative impacts on nontarget environmental exposure grouping (as proposes to use a tiered system of data organisms in the receiving water body. defined in Unit XI.B. and once-through requirements to determine the type of For the first prong, modeling would industrial processes and water systems. environmental fate assessment needed be used to estimate a screening-level These data reflect the Agency’s concern for the low environmental exposure exposure concentration of the about the potential movement of grouping. A screening-level assessment antimicrobial in a surface water body antimicrobials and their degradates from would be used to determine the that receives effluent from a WWTP. the indoor environment to the outdoor potential of the antimicrobial chemical EPA anticipates using the Down-the- environment. Additionally, these lower- to directly harm the microbial treatment Drain model with the Probabilistic tiered data will allow EPA to conduct processes present in wastewater Dilution Model (PDM) option in the screening-level environmental fate treatment systems, the environmental Exposure and Fate Assessment assessments which can then indicate the compartment(s) that the antimicrobial is Screening Tool (E-FAST) (Version 2.0) need for higher-tiered fate and likely to partition to, and the amount of available from the Agency’s website (see ecotoxicity studies and higher-tiered antimicrobial that could be present in http://www.epa.gov/oppt/exposure/ environmental assessments. the effluent that the treatment plant pubs/efast.htm). This model option uses EPA specifically requests comments releases to the environment. The readily available data as inputs to on the Agency’s rationale for requiring presence of antimicrobials in an effluent estimate conservative (i.e., high-end) data to perform a screening assessment release means that an ecological exposure concentrations. E-FAST has on down-the-drain antimicrobial uses, assessment could be required to been independently peer-reviewed by the potential for performing higher- evaluate risks to endangered species. It EPA’s Science Advisory Board. tiered studies based on the results of the is also possible that estimation of Comments from that peer review have screening assessment, and the cost and concentrations to use in a drinking been incorporated into Version 2.0 of E- burden of performing the studies. water assessment could be required. FAST. EPA also notes that three use patterns, The lower-tiered environmental fate The PDM option of E-FAST can wood preservatives, antifoulants, and studies being proposed for the predict downstream chemical aquatic uses are not considered down- screening-level assessment for the low concentrations from an industrial the-drain use patterns. As previously environmental exposure grouping are discharge and from disposal of discussed, these uses either occur discussed in detail in Units XII.E. – K. consumer products into household outdoors and thus discharge directly to of this preamble. The higher-tiered wastewater. The module uses a simple

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00027 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59408 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

mass balance approach that uses breakdown products should also be found in a biological WWTP, the probability distributions as inputs. The considered in the environmental fate Agency could determine if there are risk concentration of the chemical in the assessment. concerns. Based on the concerns, EPA receiving surface water body is also • The data from the photodegradation would be able to determine if a more in- calculated as a probability distribution in water study would allow EPA to depth risk assessment would be of the ratio of WWTP effluent flow and determine if the antimicrobial degrades required for certain environmental stream flow immediately downstream of in shallow water due to exposure to media. Higher-tiered data could be the WWTP. The Down-the-Drain Model sunlight. These data are used to required to support such a risk can be run with or without the PDM understand the persistence of a assessment. The specific data would option. chemical in surface water. depend on the environmental medium The Down-the-Drain Model requires • The modified activated sludge, in which the antimicrobial and its as an input value the production respiration inhibition test would allow transformation products reside, and on volume of the chemical. If this EPA to identify antimicrobials which the concentrations in the environment. information cannot be supplied by the could harm the microorganisms found • If the antimicrobial is completely applicant, then the Agency would need in biological wastewater treatment degraded to non-toxic degradates, then to estimate the volume. The production systems and would also indicate it is likely that no higher-tiered volume would be used as if the entire suitable antimicrobial concentrations for environmental fate data would be volume of the chemical were expected use in the ready biodegradability test. required. to go down the drain. However, the • The activated sludge sorption • If the antimicrobial is not completely Agency would be able to modify the isotherm study would allow EPA to degraded by the WWTP and is in the production volume to account for the assess the distribution of the effluent released to surface water, then percentage of the chemical that is antimicrobial between the sludge and depending on the concentrations that expected to actually go down the drain. aqueous phases. then occur in the environment, an As an example, almost all of a toilet • The ready biodegradability study assessment similar to that of an bowl cleaner can be reasonably would allow the Agency to determine antimicrobial with high environmental expected to go down the drain, but a whether the chemical tested achieves exposure could be needed. hard surface cleaner could also vaporize ‘‘pass levels’’ for ready biodegradability. • If the antimicrobial partitions to into the air, dry on the surface, or be These screening tests are so stringent water, then the possible higher-tiered disposed of on paper towels into the that it is assumed that the chemicals environmental fate studies would trash. Therefore it may be reasonable to that meet the pass levels will rapidly include: Leaching and adsorption/ adjust the production volume used as an and completely biodegrade in aquatic desorption, and aerobic and anaerobic input to the Down-the-Drain model. The environments under aerobic conditions. aquatic metabolism. model estimates human exposure from Modeling could also be used to • If the antimicrobial is likely to ingestion of drinking water and fish, predict the removal of a chemical in a partition to sludge, soil, or sediment, and concentrations of chemicals in sewage treatment plant. STPWINTM is then possible higher-tiered surface waters downstream of WWTPs. part of the EPI SUITE modeling environmental fate studies would The PDM option estimates the number available via the Agency’s website (see include aerobic and anaerobic soil of days of exceedance of a concentration http://www.epa.gov/oppt/exposure/ metabolism studies, and sediment of concern for aquatic organisms. pubs/episuite.htm). STPWINTM can studies. EPA has considered that Concentrations of concern are based on predict values not only for the total antimicrobials may be present in measurements of acute and/or chronic removal but also three contributing biosolids (sewage sludge) that are land effects to aquatic organisms. processes: Biodegradation, sorption to applied. While soil and sediment data For the second prong of the sludge, and stripping to air. would be required for an antimicrobial assessment, EPA intends to require five The third prong of the fate assessment risk assessment, these data may also be environmental fate studies to determine would use the available product useful to EPA’s Biosolids Program the potential of the antimicrobial to chemistry data (for example octanol/ conducted under 40 CFR part 503. harm the microbial treatment processes water partition coefficient, vapor The Agency specifically seeks in wastewater treatment systems, and to pressure, or solubility in water) or comment on this proposed approach for determine the potential amount of predicted/modeled data to determine performing a screening-level antimicrobial present in the effluent that the potential for the antimicrobial to environment fate assessment and the the treatment plant releases to the bioconcentrate. This is consistent with potential for triggering higher-tiered environment. Higher-tiered studies the approach used in the Agency’s PBT studies. would be triggered based on a weight- profiler, an assessment tool that D. Case Studies of-evidence evaluation of the results of estimates environmental persistence (P), the following lower tiered studies: bioconcentration potential (B), and To assess whether the proposed Hydrolysis; photodegradation in water; aquatic toxicity (T) of a chemical based approach provides the data needed to modified activated sludge, respiration on its molecular structure. (see http:// assess exposure and risk of inhibition test; activated sludge sorption www.epa.gov/oppt/pbtprofiler.) antimicrobial pesticides released to the isotherm; and ready biodegradability. The Agency would then use the environment via down-the-drain use These tests are discussed in Units XII.E., results of all three prongs to conduct a patterns, the Agency has conducted four F., H., I., and K. of this preamble. screening-level environmental fate case studies. All of the models used for • The data from the hydrolysis study assessment. It is also possible that the case studies are peer-reviewed, and would allow EPA to determine if the information from open literature could publicly available. These case studies, antimicrobial hydrolyzes in water be useful to the Agency for its entitled ‘‘Four Case Studies of during transport to the WWTP, and also assessment. By combining the modeled Antimicrobial Pesticides in the Down- after release to the environment. These exposure estimates with information on the-Drain Screening Model, Using the data are routinely used to understand the persistence of the antimicrobial, its Proposed Approach for a Screening- the persistence of a chemical in the distribution in the environment, and its Level Environmental fate Assessment’’ environment, and when the hydrolysis ability to harm the microorganisms (Ref. 42) reflect a particular integration

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00028 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59409

of the modeling results specific to the activated sludge, and fairly low toxicity TABLE 1.—CASE STUDIES—Continued needs of antimicrobials. to fish and aquatic invertebrates. Four antimicrobial pesticides that The specific identities of the Study Results have completed scientific review in the antimicrobials have been ‘‘blinded’’ to reregistration process were selected to Chemical C: An Or- There are no data to represent a range of influent volumes to focus those who may wish to comment ganic Acid that is show that Chem- WWTPs, and general environmental fate on the proposed approach, and not what Highly Soluble in ical C would harm Water microorganisms and transport properties. Antimicrobials the result ‘‘should’’ be for a particular chemical. found in biological undergoing reregistration were chosen wastewater treat- because they have fairly complete Many, but not all, of the values ment systems. supporting data bases, and are well selected for input data for the case understood; that is, they allow a studies were based on measured or Chemical D: A Mix- Chemical D does comparison of the proposed approach estimated values for existing ture of Chemicals not appear to with real-world information. antimicrobial pesticides. In some pose ecological In selecting these four chemicals, the risks at the as- instances, values for input data needed sumed production Agency attempted to select at least one to run models to assess exposure and chemical that should trigger higher tier levels. However, risk from down-the-drain releases were the potential for data requirements and one that should not available. In those instances, biodegradation trigger no higher tier data requirements. and any potential The environmental fate and transport hypothetical values were used. Hypothetical values were also impacts on waste characteristics considered during the water treatment case studies were environmental sometimes selected to enable the cases plant organisms persistence, biodegradability, hydrolytic to have sufficiently different key could not be stability, and sorption potential. environmental fate and transport ascertained with Although not intended to represent all properties to be able to more rigorously the available infor- possible combinations of chemical test the proposed tiered approach for mation. Therefore, characteristics, use scenarios, and usage assessing exposure and risk to the proposed new lower tiered envi- volumes, the four antimicrobials chemicals that are released down-the- ronmental fate selected for the case studies were drain. studies are re- intended to include a sufficiently broad quired. range of possible outcomes to credibly TABLE 1.—CASE STUDIES assess the proposed approach. From these case studies the Agency • Chemical A was intended to Study Results concludes that the proposed approach represent a chemical with a high produces the results desired by the loading (mass) within the WWTP’s Chemical A: A The proposed ap- Agency. The proposed approach influent, high toxicity to fish and Chemical that proach indicated effectively distinguishes between aquatic invertebrates, high hydrolytic Does Not Hydro- Chemical A has chemicals that will require more in- lyze and Only Par- considerable po- stability, relatively high potential to depth review and therefore higher-tiered biodegrade during wastewater tially Biodegrades tential to pose ec- ological concerns. studies versus chemicals that require treatment, and low to moderate Aerobic and an- only the lower tiered environmental fate potential to adsorb to activated sludge. aerobic soil me- and ecotoxicity studies to determine This chemical was picked as a ‘‘worst- tabolism studies that no or few additional higher tiered case’’ example. are needed to re- studies are needed. • Chemical B was intended to fine environmental The Agency specifically seeks represent a chemical with a relatively fate and dissipa- comment on the case studies (Ref. 42) low to moderate loading (mass) within tion, and higher- performed, including the assumptions the WWTP’s influent, high toxicity to tier ecotoxicity used as model inputs. EPA will consider fish and aquatic invertebrates, high studies are need- comments specific to the case studies hydrolytic stability, and no available ed to determine risk to nontarget along with comments on the proposed data on biodegradability during species. approach, as the Agency evaluates the wastewater treatment or the potential to use of the proposed approach for down- adsorb to activated sludge. Chemical B: A The proposed ap- the-drain antimicrobials in the final rule • Chemical C represents a ‘‘best-case’’ Chemical Which Is proach indicated for antimicrobial data requirements. example. It is an organic acid that has Stable to Hydrol- that the lower a high loading (mass) within the ysis, But There Is tiered environ- E. Hydrolysis Study WWTP’s influent, potential to No Data on the mental fate stud- EPA proposes to require a hydrolysis bioaccumulate, high water solubility, no Potential to Bio- ies are needed to study for all antimicrobial pesticides. In environmental fate data, and no degrade During determine Chem- 40 CFR part 161, hydrolysis studies are ecotoxicity data. This chemical was Wastewater Treat- ical B’s dissipation currently required for all use patterns ment or Adsorb to rate in wastewater except indoor. (The indoor part 161 use selected as a case study because it Activated Sludge treatment plants. degrades quickly and would be Several higher pattern is being considered by EPA to be expected to have little potential for tiered ecotoxicity similar to the low environmental ecotoxicity. studies are need- exposure grouping.) Accordingly, EPA • Chemical D represents a mixture of ed to determine proposes to continue to require two organic chemicals with relatively risk to nontarget hydrolysis studies for all of the high low loading (mass) within the WWTP’s species. environmental exposure use patterns influent volume, high resistance to (once-through industrial processes and biodegradation during wastewater water systems, antifoulant paints and treatment, low potential to sorb to coatings, wood preservatives, and

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00029 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59410 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

aquatic areas) and to codify the exposures to soils adjacent to would allow the Agency to determine requirement for all other antimicrobial preservative-treated wood structures. whether the chemical achieves ‘‘pass use patterns. In practice, hydrolysis Such soils may contain the parent levels’’ for ready biodegradability (e.g., studies have been required for all compound and/or transformation 70% removal of dissolved organic antimicrobial chemicals for over 10 products, which could include those carbon). These screening tests are so years. formed via photodegradation processes. stringent that it is assumed that As previously discussed, EPA intends antimicrobials that ‘‘pass’’ will rapidly H. Activated Sludge Sorption Isotherm to require the hydrolysis study as part and completely biodegrade in aquatic of the lower tier of environmental fate The activated sludge sorption environments under aerobic conditions. data requirements for down-the-drain isotherm study would be a new data Chemicals that degrade quickly and chemicals. Chemicals that hydrolyze requirement. EPA is proposing to completely may need few higher tiered rapidly to less toxic chemicals may need require this study only for the low studies. few higher tiered studies. This study environmental exposure grouping and will allow EPA to determine how fast the once-through industrial processes J. Porous Pot Test the antimicrobial breaks down in the and water systems. This study is not The Agency is proposing to presence of water and what degradates required for wood preservatives, conditionally require the porous pot are formed. antifoulants, or aquatic areas. study for antimicrobials based on the For antimicrobial chemicals that go results of the ready biodegradability F. Photodegradation in Water down-the-drain and reach a WWTP, as test. This would be a new data In 40 CFR part 161, the part of its screening-level environmental requirement. EPA is proposing to photodegradation in water study is fate assessment, EPA will analyze the require this study only for the low required for aquatic use patterns. The potential impact of the antimicrobial environmental exposure grouping and Agency proposes to continue its existing chemical on the microorganisms in the the once-through industrial processes requirement for a photodegradation in typical biological treatment processes of and water systems. This study is not water study for the antimicrobial a WWTP. The activated sludge sorption required for wood preservatives, aquatic areas use pattern. The Agency isotherm study would allow EPA to antifoulants, or aquatic areas. also proposes to require the study for all assess the distribution of the The porous pot study simulates the other antimicrobial uses. This would antimicrobial between the sludge and processes in the aeration basin of the expand the number of use patterns for aqueous phases. This information is activated sludge sewage treatment which this study is required. important in determining the method process. It is therefore a more realistic This study will allow EPA to used in the ready biodegradability test test than the biodegradability test. A determine the degradation of the and the higher-tiered studies that may chemical that did not ‘‘pass’’ the pesticide in shallow water bodies as a be required. Antimicrobials that are biodegradability test could degrade result of exposure to sunlight. predominantly in the water column and (partially or completely) under different Chemicals that degrade quickly in the do not sorb to sludge may not need conditions. The porous pot study would environment may need few higher tier testing that focuses on sediment and provide a measure of the extent of studies. As with the data requirements soils, such as the aerobic and anaerobic biodegradation or removal likely to for conventional pesticide chemicals, soil metabolism studies. Antimicrobials occur during sewage treatment. An EPA intends to clarify in a test note that predominantly sorb to the sludge, antimicrobial that degrades quickly and certain conditions when soil, and sediment may not need testing completely in a typical wastewater photodegradation testing would not be that focuses on water, such as the treatment plant may need few higher required. Data on photodegradation in aerobic and anaerobic aquatic tiered studies. water would not be required when the metabolism studies. electronic absorption spectra, measured K. Modified Activated Sludge, at pHs 5, 7, and 9 of the chemical and I. Ready Biodegradability Respiration Inhibition Test its hydrolytic products, if any, do not The ready biodegradability study The modified activated sludge, show absorption or tailing between 290 would be a new data requirement. EPA respiration inhibition test would be a and 800 nanometers. If no absorption or is proposing to require this study only new data requirement. EPA is proposing tailing occurs in this range, it is unlikely for the low environmental exposure to require this study only for the low that photodegradation occurs (Refs. 25 grouping and the once-through environmental exposure grouping and and 27). industrial processes and water systems. the once-through industrial processes This study is not required for wood and water systems. This study is not G. Photodegradation in Soil preservatives, antifoulants, or aquatic required for wood preservatives, The Agency is proposing to require areas. antifoulants, or aquatic areas. the photodegradation in soil study for For antimicrobial chemicals that go For antimicrobial chemicals that go wood preservatives only. Leaching of down-the-drain and reach a WWTP, as down-the-drain and reach a WWTP, as wood preservatives (both the parent or part of its screening-level environmental part of its screening-level environmental transformation products) from fate assessment, EPA will analyze the fate assessment, EPA will analyze the preservative-treated wood could potential impact of the antimicrobial potential impact of the antimicrobial contaminate the surrounding soils. This chemical on the microorganisms in the chemical on the microorganisms in the would be a new data requirement which biological treatment processes of a biological treatment processes of a would provide data on the dissipation, WWTP. Biodegradation is an important WWTP. The modified activated sludge, nature and persistence of wood environmental pathway in which the respiration inhibition test would allow preservative degradation products antimicrobial is broken down into EPA to identify antimicrobials which formed by soil surface catalyzed ‘‘smaller’’ chemicals by bacteria. This could harm the microorganisms found photolysis. Using these data the Agency study supplies information on the rate in WWTPs and thus impair the ability can assess the extent and duration of of breakdown and the completeness of of these bacteria to carry out their human (e.g., children playing below the degradation to carbon dioxide and intended function. Additionally, this decks) and/or nontarget organism water. A ready biodegradability study study would also indicate suitable

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00030 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59411

concentrations for use in the ready intermittently dry. This would codify soils, and what metabolites are formed. biodegradability test. current practices for aquatic areas. Chemicals that degrade quickly in soil For wood preservatives, the Agency are likely to have lower exposure L. Leaching and Adsorption/Desorption proposes to require an aerobic soil estimates. In 40 CFR part 161, leaching and metabolism study. This would codify adsorption/desorption studies are current practices for wood O. Aerobic and Anaerobic Aquatic required for all use patterns except the preservatives. Metabolism indoor. Accordingly, EPA proposes to The aerobic soil metabolism study In 40 CFR part 161 both the aerobic continue to require the leaching and would allow EPA to better understand and anaerobic aquatic metabolism adsorption/desorption studies for all of the antimicrobial pesticide’s studies are required for aquatic uses. For the high environmental exposure use degradation under aerobic (oxygen-rich) antimicrobial chemicals, the Agency patterns: Once-through industrial conditions in the laboratory. The results considers this to include the following processes and water systems, of the study would help to determine uses: Once-through industrial processes antifoulant paints and coatings, wood how fast the antimicrobial degrades in and water systems, antifoulant paints preservatives, and aquatic areas. the presence of microorganisms in and coatings, and aquatic areas. EPA is also proposing to conditionally different natural soils, and what Therefore, the Agency proposes to require these data for the low metabolites are formed. Chemicals that continue its current requirement for environmental exposure grouping. This degrade quickly in soil are likely to have aerobic and anaerobic aquatic would expand the number of use lower exposure estimates. metabolism studies for these uses. For patterns for which the test is wood preservatives these studies have N. Anaerobic Soil Metabolism conditionally required. For the low been required on a case-by-case basis; environmental exposure grouping, the Due to a printing error, the data therefore, this proposal would codify leaching and adsorption/desorption requirement for an anaerobic soil current practices. study is considered to be a higher-tiered metabolism study was inadvertently EPA is also proposing to conditionally study that would be triggered based on omitted from the data tables (now in 40 require these two studies for the low a weight-of-evidence evaluation of the CFR part 161) in 1991, and subsequent environmental exposure grouping. This results of the hydrolysis, publications of the CFR. EPA asserts would expand the number of use photodegradation in water, activated that this requirement is still in patterns for which the test is sludge sorption isotherm, ready existence: This data requirement was conditionally required.. biodegradability, and modified activated never intentionally removed from the Anaerobic aquatic metabolism studies sludge, respiration inhibition tests. CFR by notice and comment describe and measure the formation of The leaching and adsorption/ rulemaking, and is not considered a new pesticide residues in the water column desorption study would provide requirement. Therefore, EPA proposes or sediment under low-oxygen information on the mobility of the to adapt its current requirement for an conditions. Aerobic aquatic metabolism antimicrobial pesticide in soils. The anaerobic soil metabolism study to the studies determine the effects that antimicrobial pesticide may or may not specific needs of antimicrobial exposure to aerobic, or oxygen-rich be transported to surface water and/or chemicals by conditionally requiring the conditions in the water column or ground water bodies used for drinking study for the low environmental sediment can have on a pesticide when water. The presence of an antimicrobial exposure grouping, and wood it is dispersed through the aquatic pesticide in drinking water sources preservatives. environment. Since the degradation or could contribute to exposure via EPA is expanding the number of use dissipation pathways of pesticides in drinking water. patterns for which the test is aquatic environments are almost always conditionally required. For the low different from those of terrestrial M. Aerobic Soil Metabolism environmental exposure grouping, the systems, soil metabolism studies may The Agency proposes to adapt its anaerobic soil metabolism study is not clearly define the paths of current requirement in 40 CFR part 161 considered to be a higher-tiered study degradation found in aquatic for an aerobic soil metabolism study to that would be triggered based on a environments. For the low the specific needs of antimicrobial weight-of-evidence evaluation of the environmental exposure grouping, the chemicals. Currently, 40 CFR part 161 results of the hydrolysis, aerobic and anaerobic aquatic requires this study for terrestrial and photodegradation in water, activated metabolism studies are considered to be outdoor types of uses. sludge sorption isotherm, ready higher-tiered studies that would be The aerobic soil metabolism study biodegradability, and modified activated triggered based on a weight-of-evidence would be conditionally required for the sludge, respiration inhibition tests. evaluation of the results of the low environmental exposure grouping, For wood preservatives, the anaerobic hydrolysis, photodegradation in water, and once-through industrial processes soil metabolism study would be activated sludge sorption isotherm, and water systems. This would expand required if treated wood is used in ready biodegradability, and modified the number of use patterns for which aquatic environments or in soils which activated sludge, respiration inhibition the test is conditionally required. The may become flooded or waterlogged. tests. Chemicals that degrade quickly in aerobic soil metabolism study is This would codify current practices for water or sediment are likely to have considered to be a higher-tiered study wood preservatives. lower exposure estimates. that would be triggered based on a The anaerobic soil metabolism study weight-of-evidence evaluation of the would facilitate a better understanding P. Aquatic Sediment Studies results of the hydrolysis, of the antimicrobial pesticide’s Aquatic sediment studies are required photodegradation in water, activated degradation under anaerobic (oxygen- for aquatic use patterns in 40 CFR part sludge sorption isotherm, ready poor) conditions in the laboratory. The 161. Accordingly, the Agency proposes biodegradability, and modified activated results of the study would help to to continue its current requirement for sludge, respiration inhibition tests. determine how fast the antimicrobial aquatic sediment studies for the For aquatic areas, data would be degrades in the presence of antimicrobial aquatic areas use pattern. required only for use sites that are microorganisms in different natural EPA is also proposing to conditionally

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00031 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59412 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

require an aquatic sediment study for all by the Agency prior to the initiation of XIII. Nontarget Organisms Data other antimicrobial use patterns based the study. Details for developing Requirements on the antimicrobial’s potential for protocols are available from the Agency. A. Nontarget Organisms Data aquatic exposure. Based on past experience, the Agency For the low environmental exposure Requirements for Antimicrobials believes that these monitoring data grouping, the aquatic sediment study is EPA proposes to adapt the basic considered to be a higher-tiered study would be required only for a very small nontarget organism data types that would be triggered based on a number of antimicrobial pesticide (§ 158.2240) as listed in subpart G of weight-of-evidence evaluation of the registrations. Monitoring for tributyltin current part 158 to support applications results of the hydrolysis, antifoulants of the near coastal waters of for antimicrobial products. EPA photodegradation in water, activated the United States including the Great proposes to modify the applicability of sludge sorption isotherm, ready Lakes was required under the Organotin those requirements to antimicrobials to biodegradability, and modified activated Anti-fouling Paint Control Act of 1988. reflect differing risks and levels of sludge, respiration inhibition tests. This In 1989, pesticide registrants were exposure. Part 161 is not explicit in the would expand the number of use required to provide these monitoring data that are currently required because patterns for which the test is data under FIFRA section 3(c)(2)(B). those use patterns are not delineated conditionally required. These tributyltin antifoulants data are sufficiently for antimicrobial pesticide For the once-through industrial the only monitoring of representative U. chemicals. The proposed table, in processes and water systems, S. waters that has been required for an § 158.2240, will provide greater antifoulant paints and coatings, and antimicrobial to date. transparency and clarity. wood preservatives, data would be Ecological effects testing includes required based on the potential for R. Special Leaching Study short-term, acute, subacute, chronic, aquatic exposure and if the weight-of- The Agency is proposing to require and reproduction studies, which evidence indicates that the active special leaching studies for antifoulant progress from laboratory tests to applied ingredient or principal transformation paints and coatings, and wood field tests. These data allow the Agency products are likely to have the potential preservatives. Part 161 is not explicit in to determine if the standard for for persistence, mobility, nontarget the data that are currently required registration is met and whether aquatic toxicity or bioaccumulation. because those use patterns are not precautionary label statements This would codify current practices. concerning toxicity or potential adverse delineated sufficiently for antimicrobial The aquatic field dissipation study is effects to nontarget organisms are pesticide chemicals. This proposal used to determine the nontarget fate of necessary. a terrestrially applied pesticide that has would codify the Agency’s current The Agency is proposing to use a a high potential to enter aquatic practices. These studies are needed tiered system of ecological effects environments and to substantiate because leaching from treated materials testing to assess the potential risks of laboratory findings. The laboratory is the primary source of environmental pesticide uses to nontarget animals studies address one environmental fate exposure to antifoulants and wood (aquatic and terrestrial vertebrates and process at a time. The aquatic field preservatives. These studies would invertebrates) for antimicrobial dissipation study examines pesticide provide basic information about the pesticide chemicals. For the first tier of loss or movement in water and availability of the pesticide to the testing EPA proposes to require for all sediment. Under field conditions environment, and would be used to antimicrobial pesticides three types of degradation/dissipation processes can perform exposure and risk assessments. acute ecological effects studies. • proceed differently from how they There is no OPPTS Harmonized Avian acute oral LD50. occurred under laboratory conditions. • Acute freshwater fish LC50. guideline for these studies. The • Data from this study can reduce the applicant may perform the study with a Acute freshwater invertebrates EC50. These acute studies measure toxicity potential overestimation to both protocol of their choice, or may use the in representative species of the exposure and risk that can result from American Wood Preservers’ nontarget species most likely to be having only laboratory generated data. Association’s (AWPA) Standard Method adversely affected and allow EPA to Protocols must be approved by the of Determining the Leachability of develop precautionary labeling. Such Agency prior to the initiation of the Wood Preservatives (AWPA E11–97), labeling includes statements such as study. Details for developing protocols AWPA’s Standard Method for are available from the Agency. ‘‘This product is extremely toxic to Determining the Leachability of Wood birds’’ or ‘‘This product is toxic to fish.’’ Q. Monitoring of Representative U.S. Preservatives in Soil Contact (AWPA These statements provide needed Waters E20–04), and the American Society for information in case of unintended or co- The Agency is proposing to Testing and Materials (ASTM) Standard incident exposure to antimicrobials, conditionally require monitoring of Test Method for Organotin Release Rates such as a transportation accident. And, representative U.S. waters for all of Antifouling Coating Systems in Sea in fact, these studies are currently antimicrobial use patterns. This would Water (ASTM D5108–90), or their required for an application for include freshwater, saltwater, equivalents. As stated in the test notes registration. surfacewater, and groundwater. This to the table in proposed § 158.2280, These first tier data would be required would codify current practices. prior approval by the Agency of studies for all antimicrobial use patterns and The Agency would use a weight-of- conducted according to AWPA E11–97 performed with the technical grade evidence approach taking into account or ASTM D5108–90 is not required. active ingredient (TGAI). Higher-tiered factors such as available monitoring However, all studies that would be data would be required when the data; the vulnerability of the freshwater, conducted according to other protocols appropriate trigger in § 158.2240 is met. estuarine, or marine water resources; must be approved by the Agency prior For instance, results from these first tier and the persistence and fate of the to the initiation of the study. Details for studies may indicate the need for acute pesticide active ingredient (or developing protocols are available from toxicity testing in an additional species, degradate). Protocols must be approved the Agency. or higher-tiered studies to assess hazard

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00032 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59413

to other species or in other parts of the on the use pattern, other ecotoxicity E. Acute Aquatic Toxicity Studies environment. Other factors, such as, studies such as avian studies and TEP The Agency is proposing to require toxicity, persistence, and/or potential testing. The Agency may require acute aquatic toxicity studies (LC fish for bioaccumulation, may indicate the additional ecotoxicity studies based on 50 and EC50 invertebrate) for all need for higher-tiered ecological effects the results of these studies or on other antimicrobial uses. These studies are and environmental fate data. All typical information. needed as part of the tier one ecotoxicity end-use product (TEP) testing is testing, and as previously explained are considered to be higher tier. An D. Acute Avian Oral Toxicity used to develop precautionary labeling. applicant must carefully consider In 40 CFR part 161 acute avian studies 1. Tier 1 testing. In part 161, acute whether studies listed in the higher tier are conditionally required for ‘‘indoor’’ aquatic toxicity studies are data requirements are required for uses of antimicrobials, and are required conditionally required for ‘‘indoor’’ uses registration of his product and should for aquatic uses of antimicrobials. (The of antimicrobials, and are required for consult with the Agency, as needed. indoor part 161 use pattern is being aquatic uses of antimicrobials. The Agency has divided the considered by EPA to be similar to the antimicrobial pesticides into two groups For antimicrobial chemicals, the low environmental exposure grouping.) Agency considers the aquatic use for determining ecological effect data The Agency is proposing to require requirements, based on their expected pattern in part 161 to include the submission of acute avian LD50 toxicity following uses: Once-through industrial environmental exposure. The two studies for all antimicrobial use groupings are the same groupings used processes and water systems, patterns. These studies are needed as antifoulant paints and coatings, and for environmental fate data part of the tier one ecotoxicity testing, requirements: Low and high aquatic areas. Therefore, the Agency and as previously explained are used to proposes to continue its current environmental exposure groupings. (see develop precautionary labeling. Unit XI.B of this preamble.) requirement for two acute aquatic fish Testing in one avian species is toxicity studies (one warm water and B. The Low Environmental Exposure required for the low environmental one cold water species) and one Grouping exposure grouping. The shift from CR to invertebrate toxicity study for these use The use patterns within this grouping R for the low environmental exposure patterns. For wood preservatives these are the same as those described in Unit grouping would expand the number of three studies have been required on a XI.B. of this preamble for environmental use patterns for which this study is case-by-case basis; therefore, this fate data requirements. As previously required. proposal would codify current practices. discussed in this Unit, EPA proposes to For antimicrobial chemicals, the For the low environmental exposure require a first tier of three ecological Agency considers the aquatic use grouping, the Agency is proposing to effects studies for all antimicrobials. pattern in part 161 to include the require the acute freshwater fish toxicity These three acute ecotoxicity studies in following antimicrobial use patterns: study in one species, either a warm combination with the screening-level Once-through industrial processes and water or a cold water species. Testing on environmental fate assessment proposed water systems, antifoulant paints and a second species is required if the active to be required for assessing the impacts coatings, and aquatic areas. Therefore, ingredient or principal transformation of antimicrobial pesticides on WWTPs, the Agency proposes to continue its products are stable in the environment are the initial studies for environmental current requirement for acute avian oral or if the LC50 in the first species tested modeling for risk assessment purposes. acute toxicity studies for these uses. For is greater than 1 part per million (ppm) For the low environmental exposure wood preservatives these studies have or 1 milligram/liter (mg/L). This would grouping, higher-tiered ecotoxicity been required on a case-by-case basis; codify existing practices. Additionally, studies are conditioned on a weight-of- therefore, this proposal would codify the shift from CR to R for the low evidence evaluation of the results of the current practices. environmental exposure grouping tier one ecotoxicity studies and/or the (which contains many of the ‘‘indoor’’ As with the data requirements for results of the screening-level uses) would also codify current conventional pesticide chemicals, the environmental fate assessment. Thus, practices. Agency is proposing to change the the studies described in Unit XIII.F., G., 2. TEP testing. Typical End-Use testing requirement from one species to I., J., K., L., and M. could be triggered. Product (TEP) testing is proposed for two species for all antimicrobial use both the acute freshwater fish and C. The High Environmental Exposure patterns except the low environmental invertebrate toxicity studies. This is an Grouping exposure grouping. The change to two existing requirement according to the species is consistent with the Agency’s As with the environmental fate data test notes to the table in § 161.490. requirements, the high exposure current practices. environmental group consists of the The species proposed in this proposal F. Avian Dietary Toxicity once-through industrial processes and differ from those in the requirements for Currently in part 161 an avian dietary water systems, antifoulant paints and conventional pesticides. Many LC50 study is conditionally required for coatings, aquatic areas, and wood conventional chemicals are applied the greenhouse and indoor use patterns preservatives. These uses either occur outdoors and are considered to be and required for all other use patterns. outdoors, discharge effluent directly to terrestrial uses. For antimicrobials the Today the Agency is proposing to the outdoors, or result in materials Agency is proposing that the testing be continue this existing requirement by treated with antimicrobials (e.g., wood conducted with a waterfowl species and requiring the avian dietary study for preservatives and antifoulants) being an upland game bird species. The aquatic areas and conditionally placed in the environment, thereby selection of waterfowl and upland game requiring the study for all other leading to potentially significant species is consistent with the current antimicrobial use patterns. environmental exposure. For the high submissions by registrants of environmental exposure grouping, EPA antimicrobial products and reflects the G. Avian Reproduction proposes to require three first tier data needed for the many indoor and The Agency has adapted the current ecological effects studies and depending aquatic uses of antimicrobials. data requirements in part 161 for avian

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00033 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59414 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

reproduction testing to determine the conditionally required for the low preservative-treated wood are likely to avian reproduction data requirements environmental exposure grouping, this enter freshwater or estuarine/marine for antimicrobial chemicals. An avian would expand the number of use environments, as determined by the reproduction study is conditionally patterns for which these studies are Agency. required for aquatic uses in part 161. conditionally required. The Agency is proposing to require 2. TEP testing. For the acute estuarine J. Fish Life Cycle the avian reproduction study for the and marine studies, TEP testing is Currently, this existing data antimicrobial aquatic areas use pattern. proposed to be conditionally required requirement is conditionally required The proposed change from for the low environmental exposure conditionally required to required is grouping, once-through industrial for all antimicrobials except ‘‘indoor’’ consistent with the Agency’s current processes and water systems, and uses in part 161. The Agency is now practices. aquatic areas. This is an existing proposing to expand this conditional For all other antimicrobial use requirement according to the table in requirement to all antimicrobial use patterns, the Agency is proposing to § 161.490. patterns. conditionally require the avian The fish life cycle study is a two I. Fish Early Life Stage and Aquatic reproduction study. For wood generation reproductive study in fish Invertebrate Life-Cycle Study preservatives this study has always been that can characterize a number of considered when EPA made its case-by- The Agency proposes in § 158.2240 to sensitive life stages. Just as with case determinations on the data needed require both a fish early life stage and conventional pesticide chemicals, it is for risk assessment; therefore, this an aquatic invertebrate life-cycle study triggered on the results of the fish early- proposal would codify the current for once-through industrial processes life stage or invertebrate life cycle test, practices used for wood preservatives. and water systems, antifoulant paints or other information indicating the Since part 161 conditionally requires and coatings, and aquatic areas. For reproductive physiology of fish may be this testing for ‘‘aquatic uses,’’ the these use patterns this would codify affected. For the low environmental Agency’s proposal continues the current practices. exposure grouping, the screening-level The Agency also proposes to existing data requirement for the once- fate assessment would also inform the conditionally require both studies for through industrial processes and water determination to require this study. If the low environmental exposure systems. Since the testing is also the antimicrobial is not degraded by the grouping. This would expand the proposed to be conditionally required processes in the WWTP and is in the number of use patterns for which the for the low environmental exposure effluent released to surface water, then test is conditionally required. grouping, this would expand the this study may be required. number of use patterns for which these The Agency proposes to conditionally studies are conditionally required. require both studies for wood K. Aquatic Organisms, Bioavailability, preservatives. The studies would be Biomagnification Toxicity Tests H. Acute Estuarine and Marine Study required if pesticide residues from Acute estuarine and marine toxicity treated wood would be likely to enter This data requirement is composed of studies are performed on three species: freshwater or estuarine/marine three studies: The oyster An estuarine/marine mollusk, an environments, as determined by the bioconcentration factor, the fish estuarine/marine invertebrate, and an Agency. bioconcentration factor, and the aquatic estuarine/marine fish. These studies Currently, in part 161 only one of food chain transfer. All three studies are measure toxicity in representative these studies is conditionally required. not needed for every antimicrobial. The estuarine and marine species of the Part 161 requires the submission of most commonly submitted study is the nontarget species most likely to be either the fish early life stage or the fish bioconcentration factor. adversely affected. aquatic invertebrate life-cycle study, Currently, these studies are 1. TGAI testing. The Agency is based on the more sensitive of the two conditionally required for all proposing to require these three acute species, as determined by the acute antimicrobials except ‘‘indoor’’ uses in estuarine and marine studies for ecotoxicity studies. However, since both part 161. The Agency is now proposing antifoulant paints and coatings, and fish and invertebrates may be exposed to expand this conditional requirement conditionally require these studies for when an antimicrobial pesticide enters to all antimicrobial use patterns. For the wood preservatives. This would codify natural waters, the Agency now believes low environmental exposure grouping, the Agency’s current practices. both studies are needed. Neither study the screening-level fate assessment Testing for all other antimicrobial use would adequately substitute for the would also inform the determination to patterns would also be conditionally other. While data from acute require this study. If the antimicrobial is required. The Agency is proposing in invertebrate and acute fish studies not degraded by the processes in the part 158, subpart W to use the same would be available, EPA does not WWTP and is in the effluent released to conditionalities (as described in the test believe that these acute studies would surface water, then this study may be notes) for requiring these studies as in predict chronic sensitivity. required. part 161, i.e. the testing is required if For the low environmental exposure residues from the parent compound grouping the requirements are triggered For antimicrobials that have the and/or transformation products are if antimicrobial pesticide residues from potential to reach freshwater or likely to enter the estuarine/marine the parent compound and/or saltwater, these studies are needed to environment. transformation products are likely to identify those antimicrobials that could Part 161 conditionally requires this enter freshwater or estuarine/marine concentrate in various aquatic taxa. EPA testing for ‘‘aquatic uses.’’ Therefore, the environments, as determined by the is proposing to clarify in the test notes Agency’s proposal continues the Agency. For wood preservatives the the three specific circumstances under existing data requirement for the once- requirements are triggered if which the study is not required. These through industrial processes and water antimicrobial pesticide residues from three circumstances are the same as in systems, and aquatic areas. Since the the parent compound, transformation the final rule for conventional pesticide testing is also proposed to be products, and/or leachates from chemicals.

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00034 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59415

L. Simulated or Actual Field Testing for Testing of aquatic organisms exposed acute study for wood preservatives and Aquatic Organisms to treated sediments allows EPA to the low environmental exposure For all antimicrobial use patterns, the assess the effects of sediment-bound grouping. Since the study would be Agency is proposing to conditionally pesticide residues in aquatic required only for uses involving require simulated or field studies for environments. The effects of sediment- treatment of beehives, empty or aquatic organisms. These studies would bound pesticides (or their degradates) occupied, and since there are few such on aquatic environments cannot be be triggered when under actual use uses for antimicrobials, this study accurately assessed from bioassays on conditions significant impairment of would be infrequently required. This compounds suspended in the water nontarget aquatic organisms is likely to study may not be required if the use column alone. For example, lipophilic occur in the natural environment. This pattern (as described on the label) or hydrophobic chemicals can dissipate proposal would codify current practices. prohibits fumigating or spraying from the water column, but may remain The Agency currently determines beehives. in the aquatic environment adsorbed to whether simulated or field studies are Since beehives can be constructed of sediment. As discussed in the proposed required for antimicrobials on a case-by- materials that have been treated with rule for conventional pesticides (70 FR case basis, considering information such antimicrobials, the Agency proposes to 12275) sediment-bound pesticides may as: conditionally require a study to differ significantly from pesticides in • The pesticide’s intended use. determine the toxicity of treated wood solution, showing different physical, • The pesticide’s use rates. and other materials to bees. This study chemical, and biological properties, • The pesticide’s toxicity. must be conducted in a manner similar chemical partitioning, bioavailability, • The pesticide’s physical and to that of the Honey Bee Toxicity of concentrations in interstitial or pore chemical properties. Residues on Foliage. This would codify • water, exposure from sediment current practices. Protocols must be The parent compound’s ingestion and possible manifestations of environmental fate characteristics and approved by the Agency prior to the food chain effects. By serving as a initiation of the study. Details for transformation products (such as potential pesticide sink, exposure to metabolites and degradation products). developing protocols are available from • these compounds may lead to the Agency. Nontarget organisms likely to be significant environmental risk to a wide exposed. XIV. Plant Protection Data • variety of fish and aquatic invertebrates Likelihood of exposure. which live and feed at the bottom of a Requirements As with conventional pesticides, the lake or stream. Sediment toxicity testing A. Plant Protection Data Requirements Agency is proposing to require is needed to assess the bioavailability of independent laboratory validation of the a sediment-bound compound and to EPA proposes to adapt the basic environmental chemistry methods used characterize the possible impact to nontarget plant protection data types as to generate the data associated with this sediment-dwelling benthic organisms. listed in 40 CFR part 158, subpart G to study. Once the Agency determines or support applications for antimicrobial products. EPA proposes to modify the M. Sediment Testing extrapolates that the use pattern has the likelihood for chemical exposure to an applicability of those requirements to The Agency is proposing to require aquatic system, then the available antimicrobials to reflect differing risks acute invertebrate sediment testing, both information on the adsorption of the and levels of exposure. Part 161 is not freshwater and marine, for antifoulant chemical is reviewed. If the Agency explicit in the data that are currently paints and coatings and to conditionally determines that the antimicrobial meets required because those use patterns are require these studies for once-through one or more of the criteria for not delineated for antimicrobial industrial processes and water systems, adsorption, then the available pesticide chemicals. The proposed table wood preservatives, and aquatic areas. information on persistence of the in § 158.2250 will provide greater This would codify current practices. chemical is reviewed. If one or more of transparency and clarity. Additionally, EPA proposes to expand the criteria for persistence are met, then Plants represent the most basic the conditional requirement to all other a sediment study is required. component of any functioning antimicrobial use patterns. This study Persistence (half-life of the pesticide in ecosystem by providing oxygen and a would be triggered based on the sediment) drives the decision regarding food source for aquatic and terrestrial antimicrobials presence in the water whether the acute or chronic study is animals. Therefore, it is important to column (for example when released conducted. determine the toxicity of the from a WWTP), the potential to sorb to Before designing the protocol, antimicrobial to plants. The data sediment, and the persistence of the consultation with the Agency is needed obtained from these studies will be used antimicrobial. if the applicant is uncertain as to which to conduct nontarget plant risk The Agency is proposing to length of study is appropriate. For assessments. For aquatic environments conditionally require chronic certain antimicrobials that are highly such an assessment could include an invertebrate sediment testing, both persistent, only the chronic study may effluent from a wastewater treatment freshwater and marine, for all be required. Protocols must be approved plant being released into the antimicrobial use patterns. This study is by the Agency prior to the initiation of environment. For terrestrial triggered by the same criteria as the the study. Details for developing environments such an assessment could acute sediment study, but would be of protocols are available from the Agency. include wood preservatives in contact longer duration as determined by the with soil, land-application of biosolids, persistence of the antimicrobial. This N. Honeybee Protection or antimicrobials that partition to soil conditional requirement would codify The current data requirements for and sediment. current practices for the high testing pesticide toxicity to honeybees at environmental exposure grouping, and § 161.590 require the honeybee acute B. Requirement for Tier II Testing for Antimicrobials would then expand the requirement to contact LD50 study when honeybees are the low environmental exposure likely to be exposed. The Agency The Agency’s guidelines for grouping. proposes to conditionally require the conducting nontarget plant protection

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00035 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59416 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

studies specify two types of tests: D. The High Environmental Exposure Lemna gibba or duckweed is an Single-dose studies (referred to in the Grouping important wildfowl food source and is guidelines as Tier I tests) and multiple- The use patterns within this grouping used in wastewater reclamation. Therefore, it is important to understand dose studies (Tier II). Usually, the are the same as those described in the the impact of an antimicrobial on this applicant would conduct the single- Unit XI.B. of this preamble for food source. dose studies first, and then, based on environmental fate data requirements. the results of the single-dose studies, H. Aquatic Plant Growth (Tier II – Dose- E. Seedling Emergence (Tier II – Dose- proceed to the multiple-dose studies, Response) Response) which evaluate the effects of multiple The Agency is proposing to require dosage levels on plant growth and are This terrestrial plant toxicity test is one or more of the Aquatic Plant Growth used to determine acute toxicity levels designed to evaluate toxicity to (Tier II – Dose-Response) studies for all in comparison with environmental germinating seedlings and their ability antimicrobial use patterns. As with the concentrations. Such studies are used to to survive after chemical uptake from aquatic plant study discussed in the estimate the risk to nontarget plants and the surrounding soil. The Agency is previous section, part 161 requires the endangered plant species. proposing to require this study for the Tier I study and conditionally requires high environmental exposure grouping. Many antimicrobial pesticides are the Tier II study. For the high This proposal would codify the shift used to control plant pests such as algae environmental exposure grouping, this from the use of the Tier I study to a Tier would codify the shift from the use of in industrial processes (paper making, II study and thereby would codify cooling towers, wastewater, sewage the Tier I study to a Tier II study and current practices. thereby would codify current practices. water treatment), and residential uses The Agency is also proposing to (swimming pools, ornamental ponds, Testing is required for four species conditionally require the Tier II study representing green algae, freshwater moss growing on roofs). Some for low environmental exposure cyanobacteria, a freshwater diatom and antifoulants, ballast water treatments, grouping based on the results of the a marine diatom. These four species are and wood preservatives are also algal study. This would expand the used to represent hundreds of different intended to control plant pests. number of use patterns for which this species. Therefore, antimicrobial pesticides used study is conditionally required. Testing is required in only one for plant pest control are expected to be species (green algae) for the low phytotoxic to nontarget plants once F. Vegetative Vigor (Tier II – Dose- Response) environmental exposure grouping. This released into terrestrial or aquatic would expand the number of use environments. This terrestrial plant toxicity test is patterns for which this study is Accordingly, for all antimicrobial use designed to evaluate toxicity to young required. patterns, the Agency is proposing only plants. The antimicrobial is applied to Green algae produce oxygen, serve as the foliage to evaluate uptake of the to require multiple-dose studies, which a food source for aquatic animals, and antimicrobial from the exposed green is consistent with the testing of certain provide the basic energy needs of any tissue. The Agency is proposing to phytotoxic conventional chemicals such aquatic ecosystem. The results of the require this study for wood as herbicides which also start at Tier II. green algae study will allow the Agency preservatives and aquatic areas. For to determine if the other three aquatic In part 161, for most plant studies, the wood preservatives, this would codify Tier II study is conditionally required plant growth studies are required for the current practices. For aquatic areas, this low environmental exposure grouping. and the Tier I study is required. For would codify the shift from the use of antimicrobials, EPA believes that the the Tier I study to a Tier II study and I. Terrestrial and Aquatic Field Studies nontarget plant studies have been thereby would codify current practices. The Agency is proposing to interpreted in the context of, and The Agency is also proposing to conditionally require Terrestrial and consistent with other phytotoxic conditionally require this study for the Aquatic Field Studies for all chemicals, and this proposal would low environmental exposure grouping, antimicrobial use patterns. Field studies codify the shift from the use of the Tier and industrial processes and water provide more realistic information on a I study to a Tier II study. systems (once-through). This would pesticide’s impacts than laboratory If the applicant is in possession of expand the number of use patterns for studies which focus only on one single-dose studies that the applicant which this study is conditionally parameter, because field studies believes provide sufficient information, required. consider all potential impacts on plant growth. The need for these higher tier then the applicant is encouraged to G. Aquatic Plant Growth (Lemna gibba) studies would be based on the results of consult early in the application process (Tier II – Dose-Response) with EPA. The Agency can evaluate the the lower tier plant protection studies, information and inform the applicant as The Agency is proposing to require adverse incident reports, intended use the Aquatic Plant Growth (Lemna gibba) to the sufficiency, or the need for pattern, and environmental fate (Tier II – Dose-Response) study for the multiple-dose studies. If the applicant characteristics that indicate potential high environmental exposure grouping. does not have any studies, then exposure. This would codify the shift from the use These two studies are conditionally multiple-dose studies must be of the Tier I study to a Tier II study and required in part 161 for three use conducted. thereby would codify current practices. patterns. Due to the use patterns C. The Low Environmental Exposure The Agency is also proposing to currently used in part 161, there is not Grouping conditionally require the Tier II study sufficient delineation for comparison to for low environmental exposures based the antimicrobial use patterns proposed The use patterns within this grouping on the results of the algal study. This today. While EPA routinely considers are the same as those described in the would expand the number of use the need for these studies in Unit XI.B. of this preamble for patterns for which this study is determining the data needed for its risk environmental fate data requirements. conditionally required. assessments, it has required these

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00036 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59417

studies based on case-by-case B. FIFRA Scientific Advisory Panel ii. Residue chemistry. The Agency circumstances on a very infrequent basis (SAP) asked the SAP if the scientific approach for antimicrobials. to obtaining dietary residue information 1. 1994 meeting. In 1994, EPA held a Since the testing is proposed to be in general, but specifically for indirect 2–day meeting of the SAP to review the conditionally required for all food contact sanitizers, was reasonable. Agency’s proposed amendments to the antimicrobial pesticide use patterns, The SAP agreed that the scientific data requirements for pesticide this would expand the number of use approach was reasonable, and remarked registrations contained in 40 CFR part patterns for which these studies are extensively on the residue chemistry 158, which covered antimicrobials. The conditionally required. Additionally, data requirements for indirect food uses SAP was asked to comment on each this would harmonize the requirements such as sanitizers. They noted that such data requirement and identify, in their for antimicrobials with those of products had generally been of low scientific opinion, which requirements conventional pesticides. toxicity or low persistence, and their were necessary to fully and thoroughly belief that a tolerance or tolerance XV. Peer Review evaluate the potential hazard of a exemption for such uses was chemical compound and which were A. National Research Council unnecessary, based on FDA’s practice not intrinsically useful in providing Recommendations with such products. The SAP also practical scientific information. The suggested the use of default surface The National Academy of Sciences revisions presented to the Panel, i.e., the residue values for estimating sanitizer issued a report in 1993 entitled, changes to the data requirements residues to obviate the need for ‘‘Pesticides in the Diets of Infants and presented in this document, were measured data. Children’’ (Ref. 19). The study, generally endorsed. A very complete Although the SAP believes that a conducted by the National Research discussion of the 1994 SAP meeting was tolerance or tolerance exemption is Council (NRC), was initiated to address presented in the proposed rule for unnecessary, under FFDCA, EPA is the question of whether the current conventional pesticides (70 FR 12276). required to establish either a numerical regulatory system adequately protected 2. June 1997 meeting: A set of tolerance, or an exemption from the infants and children from pesticide scientific issues being considered by the requirement of a tolerance for indirect residues in food. The Council reviewed Agency to determine antimicrobial food uses. To obviate the need for EPA’s then-current practices and data issues. On June 3, 1997, the Agency measured data, EPA uses modeling and requirements related to dietary risk presented an early version of the part ‘‘worst-case’’ estimates, as appropriate. assessment as well as testing 158, subpart W proposal in an open As discussed in Unit X. of this modifications planned by the Agency. meeting to the SAP. The Agency asked preamble, if such estimates when paired The panel of experts concluded that, at for specific comments in five areas with the toxicity data do not indicate a that time, EPA approaches to data covered by proposed 158W data concern, then it is unlikely that requirements and risk assessments requirements: Toxicology; residue measured surface residue data would be emphasized the evaluation of the effects chemistry, ecological effects and required. of pesticides in mature animals and, in environmental fate, human exposure, iii. Human exposure. The Agency general, there was a lack of data on and efficacy. The SAP’s full comments asked the SAP if the approaches pesticide toxicity in developing are found in the docket for this action presented were reasonable and if the organisms. (Ref. 29) and are summarized here. Agency had adequately accounted for all antimicrobial use and exposure The Council’s recommendations with i. Toxicology. The Agency asked if its respect to regulatory needs for data scenarios. Additionally, the Agency division of antimicrobial pesticide uses asked if multiple exposure scenarios for development included the following: into high human exposure and low • Discussed the need to investigate the one pesticide product would be better human exposure groups, with extensive accounted for by data for all applicable effects of pesticide exposure on data requirements for high exposure immunotoxic responses in infants and exposure scenarios or a subset of uses and tiered data requirements for applicable scenarios. children. low exposure uses, was an acceptable • • The SAP agreed that the Agency’s 12 Supported the need for acute and approach. The SAP agreed that the use categories for antimicrobials were a subchronic neurotoxicity testing and Agency’s tiered approach was reasonable approach to organizing encouraged the Agency to have these reasonable, and made several exposure data requirements, and were, studies as part of the required data for suggestions to improve the proposal. in fact, similar to the approaches used all food-use pesticides. Two of these suggestions were by PMRA and the California EPA. EPA • Encouraged further work in the area ‘‘unambiguous trigger points indicating is proposing that these use categories be of developmental neurotoxicity. next Tier level of toxicity testing,’’ and codified in § 158.2201 as the Many of the NRC recommendations ‘‘to continue dialogue with Canadian antimicrobial use patterns. were incorporated into the data counterparts to harmonize, clearly • The SAP also advised that initially, requirements that were promulgated for define trigger points, and improve the all applicable exposure scenarios should conventional pesticides (72 FR 60933), guidelines.’’ be considered for a single antimicrobial and for biochemical and microbial The Agency has worked to provide product. The Agency accepted this pesticides (72 FR 60988). By clear, unambiguous triggers in the test recommendation which is now part of deliberately building on the foundation notes to the toxicology data its standard exposure assessment of these promulgated rules, and requirements tables. EPA is also practices. harmonizing to the extent practicable committed to dialogue with its • The SAP expressed concern that considering the differences in use Canadian counterpart. PMRA has post-application exposure might be too patterns, many of the NRC routinely received updates on the status narrowly defined, and noted some recommendations, such as of the draft antimicrobial data possible exposure scenarios involving immunotoxicity testing, are requirements, and has been actively persons not in the 1997 presentation. In incorporated into this proposed rule for engaged throughout the development of response, the Agency has broadened the antimicrobial pesticides. this proposal. scope of post-application exposure to

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00037 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59418 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

include persons who may come in fate and ecological effects data for The SAP cautioned that although contact with materials after treatment. conducting an ecological risk wildlife exposure to antimicrobials via This includes contact with impregnated assessment for down-the-drain water was the most likely source of materials and children’s exposure to antimicrobials. The rationale for this exposure, terrestrial exposure is also treated wood. In response, the Agency is decision is discussed in Unit XII.B. of possible. The Agency concurred, and is proposing to require the indoor surface this preamble. proposing to require for the aquatic residue dissipation study and the non- The SAP expressed its concerns about areas use pattern and to conditionally dietary ingestion exposure study for ‘‘the lack of chemical fate data,’’ and require for all other use patterns, the residential uses to address this concern. also stated that biodegradation data avian dietary and avian reproductive iv. Ecological effects and (both aerobic and anaerobic) should be studies for performing such an environmental fate. For the 1997 required. assessment. presentation to the SAP, EPA divided • In response to the SAP, EPA Finally, the SAP expressed concern the antimicrobial use sites into two reexamined the need for environmental that antimicrobial metabolites may be groupings: high expected environmental fate data other than hydrolysis, and as more toxic than their parent exposure and low expected a result of this 1997 reexamination, the compounds, and therefore may also environmental exposure. The Agency Agency determined to conditionally need to be tested. The Agency agrees, asked if a tiered data set to support an require data on photodegradation in and has revised many of the test notes ecological risk assessment for uses with water for these low expected in this proposal to clarify the need for high expected environmental exposure environmental exposures. EPA is now data on metabolites when the available was appropriate. The SAP agreed that a proposing to require the information demonstrate that the tiered data set to support an ecological photodegradation in water study for all metabolites are more toxic or otherwise risk assessment would be appropriate. antimicrobial chemicals, including the pose environmental risks. EPA also asked if ecological risk low environmental exposure grouping. 3. 1998 and 1999 meetings. Data assessments were necessary for the low • Initially, in 1997, the Agency requirements, as related to the expected environmental exposure determined to not require application of the newly mandated grouping. In its presentation EPA stated biodegradation data. EPA has FFDCA safety factor (required under the its intention to require a very reduced reconsidered this 1997 decision and FQPA amendments) were presented to data set suitable for developing today is proposing to require an the SAP in 1998 and 1999. Copies of precautionary labeling for activated sludge sorption isotherm, a documents prepared for the 1998 and manufacturing and certain end-use ready biodegradability test, and a 1999 SAP meetings and the final reports products. At that time EPA considered modified activated sludge, respiration from each of the meetings are in the that ‘‘indoor’’ uses had minimal inhibition study for the low docket for this action (Refs. 30, 31, 32, environmental exposures or releases of environmental exposure grouping. and 33) and can be found on EPA’s web pesticide residues to the environment. The SAP also questioned why site at http://www.epa.gov/scipoly/sap. The SAP commented that the reduced microbial data to protect publicly A summary of the issues specific to the data set could be justified only if data owned treatment works (POTWs) and proposed antimicrobial data available from other programs within other treatment systems which often requirements follows: EPA and elsewhere were adequate to rely on microbial treatment processes i. Toxicology. In December 1998, EPA assess ecological risk. As a result of the were not required. The Agency presented the SAP an issues paper on SAP’s concerns, the Pesticide Program investigated this possibility, but could the use of the FQPA safety factor to discussed these issues with EPA’s Office not in the early 1990s determine a address the special sensitivity of infants of Solid Waste and Office of Water. satisfactory set of data that would then and children to pesticides. The As a result of these discussions in the be useful in protecting the highly discussion on the developmental late 1990s, the Pesticide Program variable conditions of specific POTWs. neurotoxicity study was specifically continued to believe that EPA is proposing as part of its discussed in the context of the • ‘‘Indoor’’ residential uses of environmental fate data requirements, to appropriateness of using an additional antimicrobials with the rinses going require the data that would allow EPA safety factor. At that time, the SAP did down-the-drain had minimal to assess the impacts of antimicrobials not reach a consensus recommendation environmental exposures or releases of on wastewater treatment plants. on whether this study should be pesticide residues to the environment, The SAP questioned the use of routinely or conditionally required. The • Industrial effluents that could precautionary labeling to protect fish issue of what is a complete and reliable possibly contain antimicrobials would and wildlife from improper use of data set was brought before the SAP be adequately regulated via the antimicrobials, especially considering again in May 1999. The majority of the permitting process under the National that some use categories would pose Panel supported the Agency’s approach Pollutant Discharge Elimination System exposure via sewage systems. As a to applying data requirements but Program of the Clean Water Act and result, EPA prepared sample labeling to advised the Agency to revisit the first wastes possibly containing reduce this source of exposure: ‘‘This tier of required toxicity studies every antimicrobials would be adequately product is toxic to fish and aquatic few years to update data requirements regulated under the Resource invertebrates. Do not discharge effluent as needed. The Panel also agreed with Conservation and Recovery Act. containing this product into lakes, the Agency on the need to require the Therefore, in 1997, the Agency streams, ponds, estuaries, oceans, or neurotoxicity battery of studies, determined not to require public water unless this product is including developmental neurotoxicity biodegradation or microbial data. specifically identified and addressed in testing, for high exposure pesticides More recently, as part of its a NPDES permit. Do not discharge such as food-use pesticides. The SAP’s development of this proposed rule, EPA effluent containing this product to recommendations are reflected in re-evaluated its belief that ‘‘indoor’’ sewer systems without previously today’s proposed antimicrobial data residential uses had minimal notifying the sewage treatment plant requirements for developmental environmental exposures. EPA is now authority.’’ This type of labeling is still neurotoxicity and immunotoxicity. This proposing to require the environmental in use today. also harmonizes the data requirements

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00038 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59419

for conventional pesticides and for • Maintain high standards for the Regulatory Agency (PMRA), the USEPA antimicrobials. protection of human health and the and California’s EPA have been ii. Post-application exposure. environment. cooperating on a joint review for the re- Working in collaboration with Health • Increase the efficiency of the evaluation/reregistration of the Canada and the Organization for registration process by lessening the following three heavy-duty wood Economic Cooperation and resource burden on governments and preservatives: Pentachlorophenol, Development (OECD), EPA drafted the regulatory community. creosote, and chromated copper • guidelines for post-application Provide more equal access to pest arsenate. The review of submitted data, exposures studies. They were internally management tools. writing of the risk assessments, and peer • Strengthen the regulatory process. review activities are being shared. peer-reviewed and shared with the • California Department of Pesticide Facilitate the registration of Exposure data used in the preliminary alternative pest control tools. risk assessment were collected from Regulation, representatives from • Minimize trade problems. both U.S. and Canadian wood-treatment academia, and the American Crop Harmonization activities are Protection Association. The Agency facilities. Both PMRA and EPA are increasing and evolving as agencies and contributing to the public comment presented its post-application exposure applicants build upon their experiences. guidelines and standard operating process. The cooperative activities procedures to the SAP in 1998 and A. Joint Data Reviews and Evaluations continue as both EPA and PMRA work toward issuance of their decision again in 1999. In 1999, the SAP EPA is working closely with other documents in September 2008. commended the Agency for making countries toward greater uniformity in significant strides toward developing testing, reviewing and evaluating all B. Harmonization of Data Requirements scenario-based residential and non- pesticides. The benefits of international As the international regulatory occupational exposure assessments that regulatory cooperation on community works toward greater are sufficiently conservative as to not antimicrobials are potentially great: harmonization on pesticide review, underestimate exposures. The data Improved science through greater attention has also focused on the data requirements proposed for post- information exchange, and reduced requirements, how the requirements application exposure to antimicrobials regulatory and resource burdens on compare from one country to another, are drawn from this body of work. national governments and regulated and what can or should be done to 4. 2000 meeting. In its response to an parties through harmonized pesticide establish common requirements. To the April 2000 presentation on certain regulatory review. Over the last several extent that data requirements for scientific issues concerning years, substantial progress has been pesticide registration are similar, probabilistic ecological risk assessment, made toward international cooperation sharing reviews and comparing the SAP was asked for on pesticide regulatory review. Member evaluations is easier and more recommendations on sediment toxicity countries of the Organization for meaningful. Requirements that differ testing. The SAP stated that the extent Economic Cooperation and considerably from one country to to which a compound partitions from Development (OECD), including the another can mean that applicants who the aqueous phase to the sediment is a United States, have agreed upon are looking to register a pesticide in key consideration in determining the harmonized guidance for the formats of more than one country may have to need for testing benthic organisms. industry data submissions (dossiers) conduct many different studies to There was a consensus among SAP and country data review reports satisfy all the various national members that compounds with high (monographs). Countries now frequently requirements. Therefore, from the Kocs (organic carbon-water partition exchange pesticide reviews or consult perspective of the applicant, coefficient) or Kows (octanol-water with one another on key technical establishing similar requirements also partition coefficient) required sediment aspects of a review. can reduce the resources that must be testing for benthic fish or invertebrates. Under the North American Free Trade spent to conduct testing. A copy of the final report is in the Act (NAFTA), EPA has worked OECD Member countries have had docket for this action (Ref. 34) and can cooperatively with Canada and/or discussions about harmonizing be found on EPA’s web site at http:// Mexico, dividing up detailed evaluation pesticide data requirements within the www.epa.gov/scipoly/sap. Based on this work on a number of pesticides. The OECD community. The pesticide meeting, the guidelines for sediment Agency has also entered into similar industry took on the complex task of testing were developed. For information exchange and comparative looking at data requirement differences antimicrobials, acute and chronic review arrangements with other among Member countries to identify sediment testing are proposed to be countries. There have been multiple areas that might benefit from required or conditionally required. bilateral joint reviews and/or work harmonization. Preliminary findings XVI. International Activities sharing with member countries of the presented to the OECD Working Group European Union. Trilateral joint reviews on Pesticides Meeting in June 2001, EPA actively works through and workshares have been performed reported, consistent with the positions international and regional organizations with Canada and Australia. A global of scientific reviewers in OECD Member and directly with other countries to joint review is being conducted among countries, that toxicology data develop common or compatible six countries (the United States, requirements are quite similar across international approaches to pesticide Australia, New Zealand, Canada, countries. This does not mean that there registration, including data Ireland, and the United Kingdom.) The is no room for additional harmonization requirements. Joint reviews and work peer reviewers will be four other EU work on toxicology data requirements, sharing are two of the approaches used countries. The primary objective of all but rather that there are other testing by EPA to increase the harmonization of of these arrangements has been to use areas where there is much less pesticide regulatory programs. EPA resources in the most efficient way consistency on data requirements across believes that making pesticide possible. countries. regulatory programs more consistent Concerning antimicrobials, since Ecotoxicological and environmental internationally will: 2000, Health Canada’s Pest Management fate studies present a particular

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00039 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59420 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

challenge for harmonization. Data information on the existing become invasive and disrupt the native requirements in these areas can differ requirements across countries. The ecology. considerably from one country to survey served two purposes: (1) To The International Convention for The another depending upon how countries’ improve OECD’s understanding of how Control and Management of Ships’ tiered approaches to data requirements Member countries regulate biocides, and Ballast Water and Sediments, 2004 (also are applied. National data requirements (2) to provide information that could be referred to as the Ballast Water must be tied to national use patterns used to prepare the way for future Convention) was adopted by consensus and environmental and ecological efforts to increase international co- at a diplomatic conference in London on conditions. A reliable environmental operation in biocide regulation. The February 13, 2004. The U. S. delegation hazard assessment, for example, must be survey shows great variability. At this was led by the Coast Guard with based on studies that accurately reflect time OECD has no plans to work toward participation by EPA and other Federal the climate, soil types and agricultural harmonizing these data requirements, agencies. The treaty opened for practices of the country doing the but instead has worked at harmonizing signature on June 1, 2004, and will enter assessment. Because ecological and tools and methodologies in order to into force 12 months after ratification by environmental studies must be reduce duplication and harmonize 30 countries representing 35% of the representative of national conditions to review procedures for possible work world’s merchant shipping tonnage. adequately support national risk sharing. Once in force, the treaty will require assessments, harmonization of data C. Protocol/Guideline Harmonization that ships manage their ballast water to requirements for these types of studies meet discharge standards according to a can be difficult. Harmonization can Harmonization can also involve schedule in the treaty. In order to meet require extensive dialogue between protocol/guideline development or those discharge standards, ships will scientists to determine which data revisions so that the studies produced need to install equipment to treat their requirements can act as common can meet common data requirements. ballast water, including disinfection. To requirements. Such dialogue can also Issues can arise because the study date, ten countries representing 3.42% include discussions of test protocols or guidelines used to generate of the world shipping tonnage have ‘‘conditionalities,’’ that are reflected in the studies to meet the requirements can become Parties to the treaty. the test notes to the tables for the be different. In other words, a particular Although the United States has not proposed data requirements. data requirement might be the same signed the treaty, ballast water Since 1995, the United States and from one country to the next, but the discharges in U.S. waters are already Canada under the NAFTA Technical study submitted to meet the regulated by the Coast Guard under the Working Group on Pesticides, requirement can run into acceptance Nonindigenous Aquatic Nuisance Harmonization of the Evaluation of Prevention and Control Act, as amended Antimicrobial Pesticides Project have problems if done according to a protocol worked together to harmonize data that is acceptable in one country, but (16 U.S.C. 4701 et seq.) The existing requirements for antimicrobials. These not in another. There is significant Coast Guard ballast water management harmonization activities represent two commonality in protocol design for regulations can be found at 33 CFR part efforts. EPA coordinates with Canada’s toxicology studies among various 151, subparts C and D. At present, the PMRA on harmonization activities for countries, but less for ecotoxicology and Coast Guard is engaged in further all disciplines except efficacy. For environmental fate studies. Information rulemaking that would set a harmonization activities for efficacy on how to satisfy data requirements is performance standard for the quality of requirements EPA coordinates with specified in § 158.70. This section ballast water discharged in U.S. waters Health Canada’s Therapeutic Product provides for both the recommended use and which will further foster Directorate (TPD). of EPA Guidelines and for the development of ballast water treatment EPA and PMRA approach acceptability of OECD protocols with technologies. antimicrobial data requirements certain caveats. Section 158.80 allows The Agency has reviewed few differently. EPA uses a tiered testing for the use of data developed in foreign applications for ballast water strategy, while PMRA bases its data countries, again with certain caveats to treatments, presumably because such requirements on a defined use pattern ensure that the data will meet EPA’s treatments and technologies are approach. EPA and PMRA’s data needs under FIFRA and FFDCA. relatively new. Therefore, for the requirements have been carefully D. Ballast Water Treaty purpose of determining data compared. TPD and EPA recently requirements EPA determined to group completed a crosswalk of EPA and TPD Both domestically and ballast water treatments with antifoulant efficacy data requirements, which is internationally, an emerging significant paints and coatings since both have the being used for planning purposes to use of antimicrobials is the treatment of potential for exposure to marine explore future harmonization activities. ballast water. Ballast water provides organisms. OECD has not developed The data requirements proposed in this needed stability for safe operation of data requirements for ballast water. marine vessels. It is the water that is document for antimicrobials represent XVII. Research Involving Human pumped in and out of the ship’s ballast U.S. national requirements but they Subjects reflect extensive consultation with tanks to ensure safe operation, such as Canada. The data requirements are compensating for the ship’s weight Research with human subjects which harmonized to a high degree. The two changes due to loading and unloading of is conducted or supported by the U. S. countries plan to continue to work cargo. In recent years there have been government is subject to regulations for together to keep data requirements for significant concerns about transport of the protection of human subjects all disciplines as similar as possible. marine species from one marine referred to as the Common Rule. EPA OECD has not conducted any activity environment to another, via ballast was one of many federal departments specifically aimed at harmonizing data water. Ballast water treatments are and agencies who jointly promulgated requirements for biocides. In 1997– intended to kill the marine species prior the Common Rule in 1991. EPA’s 1998, the OECD Pesticide Program to discharge. When discharged into a codification of the Common Rule conducted a survey to collect new environment, a new species may appears at 40 CFR part 26, subpart A.

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00040 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59421

On February 6, 2006, EPA published intentional exposure of human subjects flexibility in the design of an integrated in the Federal Register (71 FR 6138) a are also subject to subparts K, L, and M approach in which the selection of the final rule amending 40 CFR part 26 by of 40 CFR part 26. The following data required studies as well as the design of adding nine new subparts. These requirements in proposed § 158.2260 the study protocols is influenced by the amendments extend regulatory and § 158.2270 call for studies likely to existing, reliable information about the protection to human subjects of research involve intentional exposure of human chemical. EPA is committed to moving involving intentional exposure and subjects: towards alternative testing paradigms intended for submission to EPA under • Biological monitoring studies. that are more efficient, reduce the use of the pesticide laws, when the research is • Mixer/loader or applicator exposure animal testing, take full advantage of conducted not by the Federal studies. advances in science, and provide a • government but by private parties with Post-application exposure studies. sufficient, credible amount of data for no support from Federal Common Rule If any studies undertaken to address use in a risk assessment that will departments or agencies. As these requirements involve intentional support a risk management decision. subsequently amended effective August exposure of a human subject (as defined EPA is charged with developing a 22, 2006 (71 FR 36171), this rule (1) at 40 CFR §26.1102(i)), then the study pesticide regulatory program that is forbids both EPA and third parties who must not be initiated before submission protective of human health and the intend to submit the research to EPA to of protocols and supporting environment. Other factors that also conduct new research involving documentation for review by EPA and deserve consideration in the intentional exposure of pregnant or the Human Studies Review Board. The implementation of such a program are nursing women or of children; (2) requirements for protocol submissions efficiency and effectiveness. It would be extends the substantive provisions of are specified at 40 CFR 26.1125. It may a poor use of societal resources to the Common Rule to third-party human be possible to design some studies routinely require the submission and research involving intentional exposure responsive to the proposed data governmental review of a multi-million of non-pregnant adults that is intended requirements for antimicrobials so that dollar database for every active for submission to EPA under the they do not meet the regulatory ingredient if there were alternative pesticide laws; (3) requires submission definition of research involving methods of determining which to EPA of protocols and related intentional exposure of a human chemicals could be evaluated in a information about covered human subject. If there is any question, scientifically rigorous manner using research before it is initiated; (4) however, about whether a proposed means other than measured data. From establishes an independent Human study intended for submission to EPA the Agency’s perspective an alternative Studies Review Board to review both falls within or outside this regulatory testing paradigm may also allow for a proposals for new research and reports definition, consultation with EPA is stream-lined review process for of covered human research on which recommended before initiating the chemicals of potential lower toxicity, EPA proposes to rely under the study. If EPA did not review the thus freeing resources for more in- pesticide laws; and (5) forbids EPA to protocol for a study involving depth, complex reviews of higher rely, in its actions under the pesticide intentional exposure of a human toxicity chemicals. laws, on research involving intentional subject, the study if subsequently An integrated approach would focus exposure of pregnant or nursing women submitted to the Agency would not be on using all relevant, credible or of children, or which otherwise fails acceptable under 40 CFR 26.1705. information on the chemical of interest. to meet criteria for acceptance, except in Applicants are cautioned that such an narrowly defined circumstances. XVIII. Alternative Testing Paradigms The provisions of this amended rule As with conventional pesticide approach will require a different type of directly affecting third-party research chemicals, the Agency is committed to thought process which will incorporate intended for submission to EPA are 40 moving towards a more efficient and significantly more planning and ‘‘data CFR part 26, subparts K, L, and M. refined testing/risk assessment mining’’ types of activities than making Subpart K extends the substantive paradigm for antimicrobial pesticide arrangements to conduct the required provisions of the Common Rule to third- chemicals. studies. However, it could also offer a party research involving intentional flexibility that is not always present A. Structure Activity Relationship (SAR) exposure of non-pregnant adult subjects under the currently-used, guideline- that is intended for submission to EPA EPA must rely upon information of driven (study-by-study) approach. under the pesticide laws. Subpart K also appropriate quality and reliability for Both SAR and QSAR techniques play requires submission to EPA of proposals each decision made by the Agency. In a critical role in an integrated approach. for any covered research for review by the Office of Pesticide Programs (OPP), In the SAR process, a chemical’s EPA staff and the Human Studies the evaluation process for a pesticide molecular structure is compared to that Review Board before it is initiated, and chemical traditionally begins with the of other chemicals for which data are specifies the range of information applicant’s submission of a set of available. These structural similarities required to support any such proposal. studies conducted with the specific are then used to make predictive Subpart L prohibits conduct of any new pesticide chemical of interest. The use judgments about a chemical’s physical, third-party research intended for of the results of such testing (measured chemical, and biological properties. submission to EPA involving intentional data) is a logical, scientifically-rigorous Thus, the chemical’s physical, chemical, exposure of pregnant or nursing women process that identifies the physical, and biological properties are a function or of children. Subpart M specifies the chemical, and environmental fate of (or directly related to) the chemical’s range of information required to be properties of the pesticide, as well as molecular structure. Quantitative SAR is submitted with every report of the dose and endpoints at which an referred to as QSAR. To develop a completed research with human adverse effect can occur in various QSAR, a selected set of measured data subjects to document its ethical animal species. on a single physical, chemical, or conduct. Today, there is significant interest in biological property are used to derive a Studies required under proposed 40 determining alternative testing model (an equation) to predict the value CFR part 158, subpart W which involve paradigms that could offer more of that property.

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00041 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59422 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

EPA’s Office of Pollution Prevention microbial, and antimicrobial pesticide using different sets of data) would and Toxics administers two programs, chemicals. The Agency specifically necessarily have trade-offs. Therefore, the Interagency Testing Committee (ITC) seeks comment on this issue. Comments QSAR models must be used with and the New Chemicals Program (NCP) will be used in the further development caution. Expert judgment is required to under the Toxic Substances Control Act, of SAR and QSAR approaches for determine the appropriate model to use that have been using various forms of fulfilling data requirements, but will not and if the results of the model strike the SAR and QSAR since the late 1970s. be addressed in the final rule for correct balance of accuracy and The ITC is an independent advisory antimicrobial data requirements. precision, with the potential for few committee that screens chemicals or Those applicants considering use of false negatives or false positives. classes of chemicals and prioritizes SAR and QSAR as part of a submission At this time, EPA believes that for them for testing. The NCP uses an package to OPP should realize SAR and certain endpoints, especially physical/ expert judgment SAR process to assess Quantitative SAR (QSAR) modeling chemical and fate properties, that SAR human health and has developed QSAR results can sometimes be used instead of and QSAR might be effectively utilized models to evaluate physical, chemical measured data, but modeled data cannot to fulfill these data requirements for and environmental fate properties and be preferentially substituted for well- many antimicrobial pesticide chemicals. ecological effects. conducted studies (measured data). If When considering biological properties, Additionally, other agencies (both measured data are available for a EPA believes that SAR and QSAR can U.S. and non-U.S.) are investigating particular endpoint, then the measured be most effectively utilized in the how to use these alternative techniques. data should carry the greatest weight for evaluation of chemicals that exhibit OECD has devoted a significant amount hazard and risk assessment purposes. lower toxicity for human health and/or of time and effort to coordinating model Applicants are cautioned that if the ecotoxicity parameters. This is development and model validation for Agency determines that the SAR and/or appropriate because the risk assessment such an integrated approach. EPA has QSAR do not fulfill the data for lower toxicity chemicals can be participated on these workgroups. requirement, then the registration may streamlined, i.e., through use of a During the last 6 years, OPP has made be delayed while a study (measured screening-level assessment procedure increasing use of SAR as part of its data) is generated according to part 158 rather than multiple tiers of assessments regulatory decision-making process. requirements. with progressively more data Documents to establish tolerance At this time, the Agency intends to requirements. exemptions, documents to support continue its initial explorations and As appropriate, OPP will consider the tolerance reassessment, and begin the process to shift from the use of SAR and/or QSAR predictive Reregistration Eligibility Decision current guideline-driven (study-by- techniques as part of the hazard Documents have incorporated the use of study) approach to a more integrated assessment, and eventually the dose and SAR, when appropriate. OPP recognizes approach in which the use of predicted endpoint selection process for the usefulness of incorporating data, generated using validated models, antimicrobial chemicals. Under a predictive techniques into its hazard is considered along with information QSAR-based approach an applicant and risk assessments, and that for from open literature and studies could provide the Agency with an certain chemicals SAR assessments and specifically generated under part 158 analysis that could frame the actual data QSAR modeling could potentially form data requirements. All relevant required to register the antimicrobial a scientifically-sound basis for hazard information would be considered as part pesticide chemical. For some and risk assessments used for regulatory of a weight-of-evidence evaluation. antimicrobials, applicants may have the decisions. Over time, OPP has The shift to an integrated approach option of characterizing certain of the progressed from using SAR techniques would occur over some time. OPP has active ingredient properties via to support a dataset of guideline type deliberately chosen to begin this shift predictive techniques. It is the studies to, for certain assessments, with antimicrobial pesticide chemicals responsibility of the applicant to relying on SAR techniques as an instead of conventional pesticide provide sufficient information to acceptable source of information on the chemicals for two reasons: First, most conduct a risk assessment that can be chemical. OPP is now considering when conventional pesticide chemicals are used to support a risk management and how to codify in subpart A of deliberately created for their biological decision. If the applicant believes that a current part 158 that information activity and many require complex risk SAR assessment and/or QSAR model derived from SAR assessments and/or assessments. Few conventional would provide scientifically credible QSAR modeling could be acceptable for pesticides have non-pesticidal uses. information that would be useful to fulfilling a data requirement. The Second, antimicrobials also have EPA, then it is the responsibility of the submitter of such information would be biological activity, but are more likely to applicant to provide to the Agency a expected to supply a rationale have non-pesticidal uses and, in fact, rationale on the appropriateness of SAR describing the utility of the information may have been assessed by other or QSAR for that particular endpoint and provide documentation on the regulatory agencies. The ready and sufficient documentation on how scientific validity of the information. availability of published literature and the assessment and/or model is The determination that the predicted publicly-available assessments offer a scientifically valid. Without such data fulfills the data requirement would unique opportunity for the applicant to information OPP cannot judge the be at the sole discretion of the Agency. use the available information as a validity of the model and therefore the The Agency seeks comment on the use starting point for fulfilling data acceptability of the results of the model of predictive techniques to fulfill the requirements, and offering the possible for OPP’s decision-making purposes. part 158 subpart W data requirements, option, when appropriate, of SAR and At this time, the use of SAR is not yet and specifically on when and if the use QSAR for those data requirements that a standardized approach in OPP, and is of SAR and QSAR should be codified in are not yet fulfilled by measured data. being handled on a case-by-case basis. part 158, subpart A. Codification in part It should be realized that just as Therefore, OPP has not yet developed a 158, subpart A means that SAR and measured data have uncertainties, standardized format for submission of QSAR techniques would be applicable predicted data also have uncertainties. such information. Further information to conventional, biochemical and Use of different models (developed on OPP’s current thinking on how SAR

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00042 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59423

and QSAR modeling can be used as part that examine age-related sensitivity or information would be the triggers, that of an integrated approach to hazard and susceptibility to chemical exposure, and is, the points at which a concern is risk assessment to support a regulatory information on potential or actual indicated and thus a higher level of decision-making process and guidance exposure to humans. These data could testing is needed. The retrospective on submission formats is contained in be used to inform a more targeted analyses will aid the Agency in the support document, ‘‘Use of testing approach in the design of confirming the proposed ACSA triggers Structure-Activity Relationship (SAR) studies, or to support a position that the or in determining new ones. Once the Information and Quantitative SAR requirement for specific toxicology tests analysis is complete, EPA will be able (QSAR) Modeling For Fulfilling Data should be waived (i.e., the studies are to complete draft guidance on testing. Requirements for Antimicrobial not needed)or fulfilled via a means EPA plans to request SAP review and Pesticide Chemicals and Informing other than data generation, such as SAR. public comment of the analyses and EPA’s Risk Management Process’’ which ACSA represents the first draft guidance in 2008. is contained in the docket for this comprehensive effort to scientifically re- Additionally, there are plans to proposed rule (Ref. 43). The Agency design the toxicology animal-testing conduct several case studies using the specifically seeks comment on this framework for pesticide chemicals. A ACSA tiered testing proposal. It is support document. series of reports authored by HESI/ILSI essential to test how the ACSA scheme were published in a special edition of B. International Life Sciences Institute works in practice. From such case the Journal of Critical Reviews in studies, EPA will be able to assess the and Health and Environmental Sciences Toxicology in January 2006 (Refs. 1, 2, Institute Approaches feasibility of a testing laboratory’s 3, and 6). These four articles ability to perform such a complex study, In both the proposed (70 FR 12276) summarized the initial findings and and will have the opportunity to and final (72 FR 60934) rules for recommendations. evaluate the ability of the approach and conventional pesticide chemicals, EPA The ACSA proposal is consistent with its parameters to characterize known EPA’s direction and goals to develop a discussed the relevance and importance toxicants and address risk assessment more efficient and reliable testing of the ILSI/HESI project. There have needs. paradigm. The ACSA approach departs been discussions on alternative testing In considering regulatory changes to paradigms with the International Life significantly from the current standardized list of hazard studies used reflect the results of EPA’s consideration Sciences Institute (ILSI) Health and of ACSA, the Agency will develop Environmental Sciences Institute (HESI) by many national and international authorities to assess pesticides. Some scientific position papers on the new under the Agricultural Chemical Safety approach and recommendations for Assessment (ACSA) Technical studies could be eliminated while endpoint coverage might be increased in internal and external review. Internal Committee, since 2001 (Ref. 14). The review includes review by the FIFRA focus of this effort has been toxicity redesigned studies based on responses observed in a core set of toxicity tests. SAP and opportunities for public testing for agricultural chemicals, but comment. External peer review and the results would also be applicable to Thus, it will be essential to conduct retrospective and prospective data acceptability by other national and antimicrobial pesticides. international regulatory authorities are This project, with the participation of analyses to determine whether this new considered before implementation of EPA scientists, represents an evolution testing paradigm will meet EPA’s risk any new testing paradigm and data of the current paradigm of animal (in assessment needs. requirements. Harmonization of data vivo) toxicity testing toward a more The first retrospective analysis has requirements with our NAFTA and integrated tiered testing approach for been completed for the 1–year chronic OECD partners is also an important pesticide chemicals. Under this dog study. Based on this retrospective factor. International regulations integrated approach, both the selection analysis, which was reviewed by the currently require studies that were of studies that would be required, as FIFRA SAP, the 1–year chronic dog omitted in ACSA. If EPA had well as the design of the tests study is no longer required for requirements that were significantly themselves, could be influenced by conventional pesticide chemicals and is different from those of the international other substantive and reliable not proposed as a data requirement for community, then there could be information about the pesticide. antimicrobial chemicals. Another The goals being pursued by EPA for retrospective analysis on the 2- significant problems for applicants in this next generation of toxicity testing generation reproductive toxicity study is trying to satisfy multiple and different are to: underway. To this end, the Office of requirements world-wide. • Incorporate advances in science and Pesticide Programs is currently working Thus, as these analyses and the technology in an expeditious manner. with EPA’s National Center for needed peer reviews are completed, • Identify cost effective and Computational Toxicology to populate a EPA will have the opportunity to scientifically sound alternatives to Toxicological Reference Database determine if the new testing paradigm current animal tests. (ToxRef) with data from the rat 2- will meet its risk assessment needs. EPA • Define a transparent, step wise plan generation reproductive study, prenatal will then be able to determine what that leads to an evolution, not developmental toxicity and systemic revisions to current data requirements revolution, in testing and assessment. toxicity studies on hundreds of and testing guidelines may be • Define a clear and credible process, pesticides that represent different appropriate. with external peer-review and classes, modes of action, and toxicity C. Computational Toxicology stakeholder participation. profiles. EPA will use this relational All available information would be database to determine the value of EPA’s Office of Research and considered: Not only toxicity and dose- endpoints currently evaluated in risk Development (ORD) established the response data from other guideline or assessment (i.e., the F1 versus F2 National Center for Computational non-guideline studies, but also responses). Toxicology (NCCT) in 2005. The NCCT structure-activity relationships, data on From these analyses the Agency will is developing computational tools for the mechanism or mode of action of the gain other information critical for interpreting data from computational chemical, pharmacokinetic data, studies gaining scientific consensus. Such chemistry, high-throughput screening

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00043 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59424 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

(HTS) and genomic technologies as impact of chemicals on biological identification and dose-response follows: pathways critical for the function of assessment. • Computational chemistry is the systems such as the heart, lungs, brain, • Breadth, providing data on the integration of modern computing and or reproductive organs quickly and in a broadest possible universe of chemicals, information technology with cost-efficient manner. Thus, results from endpoints, and life stages. information on molecular biology and these bioassays will provide a • Animal welfare, causing the least chemistry to predict bioactivity profiles. comprehensive and detailed overview of animal suffering possible and using the • HTS is a system to rapidly and the potential impact of environmental fewest possible animals. efficiently test large batches of chemicals upon key cellular activities. • Conservation, minimizing the chemicals for bioactivity utilizing As the ToxCastTM database grows so expenditure of money and time on robotics and automation applied to will confidence in the models testing and regulatory review. molecular biology and assay methods. developed from that data, as well as the The report acknowledged that it was • Genomics is the study of all the resultant predictions of toxicity and difficult to simultaneously meet all four genes of a cell or tissue, and their potential mechanisms of action derived objectives. function. from the models. This could result in EPA’s ToxCastTM Program began in In 2007 NAS released its Part II report changing and/or reducing the use and 2006. The underlying hypothesis for entitled ‘‘Toxicity Testing in the 21st numbers of animals in toxicity testing. ToxCastTM is that an organism’s Century: A Vision and a Strategy’’ (Ref. This could also result in fewer in vivo toxicological response is driven by 21). According to NAS, toxicity testing tests being conducted as scientists and interactions between chemicals and is approaching a ‘‘scientific pivot regulators learn how to interpret and biomolecular targets. ToxCastTM also point.’’ Today, there are advances in the use ToxCastTM predictions to then includes model development to predict biological sciences that are already determine the chemicals that must be the potential toxicity of environmental impacting how toxicity testing is tested using traditional toxicity testing. chemicals based on bioactivity profiles. conducted. NAS concluded that a Results from the first phase of These models will identify predictive paradigm shift would be needed to ToxCastTM are anticipated by the signatures, derived from the bioassay transform the current testing system but summer of 2008. However, significant data. This means that EPA under that ‘‘the result will be a more efficient, effort will be needed as ToxCastTM ToxCastTM will develop methods of informative and less costly system for transitions from proof-of-concept to a prioritizing chemicals for further assessing the hazards posed by useful prioritization tool. screening and testing to assist the industrial chemicals and pesticides.’’ Agency’s programs in the management D. National Academy of Sciences (NAS) E. Next Steps and regulation of environmental Report Concerning Toxicity Testing and contaminants (Ref. 5). Assessment of Environmental Agents EPA will undertake rule-makings on a There are three phases to the timely basis as the science progresses EPA asked NAS to undertake a development of ToxCastTM: and changes to the data requirements 1. The proof-of-concept phase of comprehensive review of established are appropriate. and emerging toxicity-testing methods ToxCastTM will examine more than 300 XIX. Animal Welfare Concerns chemicals, with rich toxicological and strategies. In response to this databases, in over 400 different HTS request NAS convened the Committee The Agency understands many bioassays. Predictive signatures will be on Toxicity Testing and Assessment of people’s concern about the use of created by correlating the HTS bioassay Environmental Agents. EPA asked the animals for research and data data to the known toxicity of the 300 Committee to conduct their assessment development purposes. In both the chemicals. in two parts. Part I is a review proposed rule (70 FR 12276) and in the 2. A signature evaluation and document, discussing current and near- final rule (72 FR 60934) for expansion phase will focus on testing term methods and strategies for conventional pesticide chemicals, EPA and extending the ToxCastTM predictive collecting information for human health discussed its commitment to the signatures, through the generation of risk assessment. Part II is a long-range development and use of alternative HTS data on over 1,000 additional vision and strategic plan for changes to approaches to animal testing. chemicals. human health risk assessment Taking into consideration principles 3. The application phase of ToxCastTM paradigms. of sound science and the requirements will be expanded to include a variety of In June 2006, NAS released Toxicity of FIFRA to protect humans and the high-priority chemicals that are either Testing for Assessment of environment, the Agency is committed regulated and/or considered for Environmental Agents: Interim Report to avoiding unnecessary or duplicative regulation by EPA and potentially (Ref. 20). This report fulfills EPA’s Part animal testing. As a result, the Agency thousands of environmental chemicals I request. In conducting its research has invested significant resources to requiring prioritization. ToxCastTM is NAS considered numerous documents investigate more integrated testing envisioned as delivering an affordable, and resources such as (1) current approaches that include, in silico, in science-based system for categorizing toxicity testing protocols and various vitro, and focused in vivo testing. The chemicals. testing strategies using these protocols, Agency’s long-term goal is to create a In 2007 the NCCT awarded nine (2) impediments to the use of human testing paradigm so that chemicals are contracts for the generation of HTS and data, (3) strategies that rank or screen tested in animals only for those genomics data as part of the ToxCastTM chemical substances, and (4) human endpoints most relevant to each chemical prioritization research health risk assessment guidance chemical’s exposure or intended use. program, in order to develop the ability documents. The Part I report identified The Agency acknowledges that to predict, or forecast toxicity based on four objectives that EPA should strive to substantial work remains to achieve this bioactivity profiling. State-of-the-art meet as it works to evolve its current long-term goal, but the Agency is also HTS and genomic approaches paradigm of toxicity testing: working on the important short-term developed by the pharmaceutical • Depth, providing the most accurate, goal to make the existing animal testing industry provide information on the relevant information possible for hazard paradigm more efficient, reliable, and

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00044 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59425

responsive to its risk assessment and will be much more difficult to delineate, 7. Food and Drug Administration management needs. and overlay with endangered or (FDA) (January 1993). Sanitizing As a result of the Agency’s activities threatened species locations. Solutions: Chemistry Guidelines for to move towards a more efficient animal The Agency seeks comment on: Food Additive Petitions. (accessed July paradigm, EPA is proposing to eliminate 1. The types of data that could be 2, 2008) http://www.cfsan.fda.gov/ the existing requirement for the 1–year useful for conducting the assessment ~dms/opa-cg3a.html. chronic dog study for antimicrobial required. 8. FDA (April 2002a). Guidance for pesticide chemicals. 2. Projections of how long it would Industry: Preparation of Premarket XX. Potential Rule-Makings of the take to generate the needed data. Notifications for Food Contact Future for Endangered Species 3. Whether antimicrobial use sites can Substances: Toxicology be adequately correlated with Recommendations. (accessed July 2, EPA is charged with protecting endangered species locations, and 2008) http://www.cfsan.fda.gov/~dms/ endangered and threatened species from suggested methods for doing so. opa2pmnt.html. potential harm from pesticide use. 9. FDA (April 2002b). Guidance For Under the Endangered Species Act, EPA XXI. References Industry: Preparation of Food Contact must ensure that the registered uses of 1. Barton, A, Pastoor, TP, Baetcke, K, Notifications and Food Additive pesticides will not jeopardize the Chambers, JE, Diliberto, J, Doerrer, NG, Petitions for Food Contact Substances: continued existence of endangered or Driver, JH, Hastings, CE, Iyengar, S, Chemistry Recommendations. Final threatened species, or adversely modify Krieger, R, Stahl, B, and Timchalk, C. Guidance. (accessed July 2, 2008) http:// habitat designated as critical by the U.S. 2006. The acquisition and application of www.cfsan.fda.gov/~dms/ Fish and Wildlife Service or National absorption, distribution, metabolism, opa2pmnc.html. Marine Fisheries Service. Accordingly, and excretion (ADME) data in 10. FDA (August 2006) Estimating in its proposed and final rules for both agricultural chemical safety Dietary Intake of Substances in Food conventional pesticide chemicals, and assessments. Critical Reviews in (accessed July 2, 2008) http:// biochemical and microbial pesticide ~ Toxicology. 36, 9–35. www.cfsan.fda.gov/ dms/opa2cg8.html chemicals, the Agency discussed the 2. Carmichael, NG, Barton, HA, 11. FDA (December 2007) Guidance possibility of future data and for Industry: Preparation of Premarket information needs to develop and/or Boobis, AR, Cooper, RL, Dellarco, VL, Doerrer, NG, Fenner-Crisp, PA, Doe, JE, Submissions for Food Contact refine risk assessments for endangered Substances: Chemistry and threatened species. As a result of Lamb, JC, and Pastoor, TP. 2006. Agricultural chemical safety assessment: Recommendations. (accessed July 2, those proposed rules, EPA received 2008) http://www.cfsan.fda.gov/~dms/ comments. For the present, EPA will a multi-sector approach to the modernization of human safety opa3pmnc.html consider those comments in the context 12. Halden, R, and Paull, D. 2005. Co- requirements. Critical Reviews in of its ongoing risk assessments, Occurrence of Triclocarban and Toxicology. 36, 1–7. including those for antimicrobials. If Triclosan in U.S. Water Resources. 3. Cooper, RL, Lamb, JC, Barlow, SM, EPA finds that it needs to amend Environmental Science and Toxicology. Bentley, K, Brady, AM, Doerrer, NG, subpart W of part 158 to normalize 39: 6, 1420–1426. endangered species data requirements, Eisenbrandt, DL, Fenner-Crisp, PA, 13. Health Canada, Pesticide it will consider those comments and any Hines, RN, Irvine, L, Kimmel, CA, Management Regulatory Agency: comments submitted in response to this Koeter, H, Li, AA, Makris, SL, Sheets, L, Memorandum from Don Grant, Director proposed rule in the development of a Speijers, GJA, and Whitby, K. 2006. A Health Evaluation Division: future proposed rule. tiered approach to life stages testing for Reproductive Toxicity Testing in For agricultural pesticides, there is agricultural chemical safety assessment. Proposed 40 CFR 158, Subdivision W - generally greater specificity relative to Critical Reviews in Toxicology. 36, 69– Data Requirements for Antimicrobial where a pesticide may be used. If 98. Pesticides. December 1, 1997. adequate geographic delineation of the 4. Dearfield, KL, Auletta, AE, Cimino, Attachment to Memorandum: The use site is possible, then overlap with MC, and Moore, MM. 1991. Assessment of Reproductive Toxicity for the locations of an endangered or Consideration in the U. S. Antimicrobial Pesticides: The Tiered threatened species may also be possible. Environmental Protection Agency’s Approach of USEPA and Proposals for However, antimicrobial pesticides are Testing Approach for Mutagenicity. Change; November 1997 draft. different from agricultural pesticides. Mutation Research. 258, 259–283. 14. International Life Sciences The Agency expects that most 5. Dix, DJ, Houck, KA, Martin, MT, Institute, Health and Environmental antimicrobial uses with potential for Richard, AM, Setzer, RW, Kavlock, RJ. Sciences Institute Developing strategies environmental exposure (e.g., wood 2007. The ToxCast Program for for agricultural chemical safety preservatives, antifoulant paints, Prioritizing Toxicity Testing of evaluation, a report from an April 22– industrial wastewater discharges, ballast Environmental Chemicals; Toxicological 23, 2001 workshop. (September 2001) water discharges) could impact Sciences 95(1), 5–12 (accessed July 2, 15. Luster et al. 1992. Risk geographic areas of the United States 2008) http://toxsci.oxfordjournals.org/ Assessment in Immunotoxicology I. that are less well defined. For example, cgi/content/abstract/95/1/5. Sensitivity and Predictability of vessels treated with antifoulant paints 6. Doe, JE, Boobis, AR, Blacker, A, Immune Tests, Fundamental and can occur in freshwater, estuarine, or Dellarco, VL, Doerrer, NG, Franklin, C, Applied Toxicology. 18: 200–210. marine areas within the U.S. (such as Goodman, JI, Kronenberg, JM, Lewis, R, 16. Luster et al. 1993. Risk lakes and rivers) and in coastal waters. McConnell, EE, Mercier, T, Moretto, A, Assessment in Immunotoxicology II. Wood preservatives could be used in Nolan, C, Padilla, S, Phang, W, Solecki, Relationships Between Immune and locations that may result in an impact R, Tilbury, L, van Ravenswaay, B, and Host Resistance Tests, Fundamental and to terrestrial and/or aquatic organisms Wolf, DC. 2006. A tiered approach to Applied Toxicology. 21: 71–82. depending on the use of the wood, systemic toxicity testing for agricultural 17. McAvoy, D, Schatowitz, B, Jacob, which could occur throughout the chemical safety assessment. Critical M, Hauk, A, and Eckhoff, W. 2002. United States. Antimicrobial use sites Reviews in Toxicology. 36, 37–68. Measurement of Triclosan in

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00045 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59426 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

Wastewater Treatment Systems. Being Considered by the Agency to Health Effects Division/Office of Environmental Toxicology and Determine Antimicrobials Issues Pesticide Programs. Chemistry, 21: 7, 1323–29. (accessed July 1, 2008) http:// 39. USEPA (January 2007) FIFRA SAP 18. Marzulli, F. and Maibach, H. www.epa.gov/scipoly/sap/meetings/ Meeting Minutes (accessed June 25, Dermatotoxicology (5th ed.). page 284. 1997/june/antimicr.htm. 2008) http://www.epa.gov/scipoly/sap/ 19. National Research Council, 30. USEPA FIFRA SAP Meeting of meetings/2007/january/ ‘‘Pesticides in the Diets of Infants and December 1998: A Retrospective january2007finalmeetingminutes.pdf. Children,’’ National Academy Press, Analysis of Twelve Developmental 40. USEPA (April 2, 2007) Human Washington, D.C., 1993. Neurotoxicity Studies (Draft 11/12/98) Studies Review Board Meeting Minutes 20. National Research Council 2006. (accessed July 1, 2008) http:// (EPA-HSRB–07–02) (accessed June 25, Executive Summary: Toxicity Testing www.epa.gov/scipoly/sap/meetings/ 2008) http://www.epa.gov/OSA/hsrb/ for Assessment of Environmental 1998/december/neuro.pdf. files/ Agents: Interim Report. (Note: click on 31. USEPA FIFRA SAP Report No. April2007HSRBMtgFinalReport.pdf. download free executive summary) 99–01B: II - A Retrospective Analysis of 41. USEPA (February 5, 2007) (accessed July 1, 2008) http:// Twelve Developmental Neurotoxicity Appendix B – Antimicrobial Product www.nap.edu/catalog/11523.html. Studies (January 22, 1999) (accessed Use Sites and Categories Index. USEPA, 21. National Research Council 2007. July 1, 2008) http://www.epa.gov/ Antimicrobials Division, Office of Executive Summary: Toxicity Testing in scipoly/sap/meetings/1998/december/ Pesticide Programs. the 21st Century: A Vision and a final2.pdf. 42. USEPA (December 31, 2007). Four Strategy (Note: click on download free 32. USEPA FIFRA SAP Meeting of Case Studies of Antimicrobial Pesticides executive summary) (accessed July 1, December 1998: Toxicology Data in the Down-the-Drain Screening Model, 2008) http://www.nap.edu/catalog/ Requirements for Assessing Risks of Using the Proposed Approach for a 11970.html. Pesticide Exposure to Children’s Health. Screening-Level Environmental Fate 22. Santa Clara Basin Watershed (Draft—November 30, 1998). http:// Assessment. USEPA, Antimicrobials Management Initiative. 2006. White www.epa.gov/scipoly/sap/meetings/ Division, Office of Pesticide Programs. Paper: Environmental Emergence of 1998/december/10xreq.pdf. 43. USEPA (December 17, 2007). Use Triclosan.(accessed July 2, 2008) http:// 33. USEPA FIFRA SAP Meeting of of Structure-Activity Relationship (SAR) www.scbwmi.org/PDFs/ May 1999: Toxicology Data Information and Quantitative SAR WMI_Triclosan_FinalJan06.pdf. Requirements for Assessing Risks of (QSAR) Modeling For Fulfilling Data 23. Singer, H, Muller, S. Tixiewr, C., Pesticide Exposure to Children’s Health. Requirements for Antimicrobial and Pillonel, L. 2002. Triclosan: (Draft—April 28, 1999). (accessed July 1, Pesticide Chemicals and Informing Occurrence and Fate of a Widely Used 2008) http://www.epa.gov/scipoly/sap/ EPA’s Risk Management Process. Biocide in the Environment: Field meetings/1999/may/10xtx428.pdf. 44. USEPA (2008). Economic Analysis Measurements in Wastewater Treatment 34. USEPA FIFRA SAP Meeting of of the Proposed Data Requirements for Plants, Surface Waters, and Lake April 2000: Implementation Plan for Antimicrobial Pesticides, EAB/BEAD/ Sediments. Environmental Science and Probabilistic Ecological Assessment OPP. Toxicology. 36: 23, 4998–5004. (August 2, 2000). (accessed July 2, 2008) 45. USEPA (August 26, 2008). 24. USEPA Federal Register Notice. http://www.epa.gov/oscpmont/sap/ Supporting Statement for an Toxicology Data Call-In for meetings/2000/april/ Information Collection Request (ICR), Antimicrobial Pesticides (January 7, freportapril572000.pdf. Data Requirements for Antimicrobial 1987) (FRL–3136–3). 35. USEPA (November 28, 2001). Pesticides (Proposed Rule), EPA ICR No. 25. USEPA (March 9, 1992). General Principles for Performing 2318.01, OMB Control No. 2070–(new). Environmental Fate and Effects Division Aggregate Exposure and Risk Policy Note 1–2: Waiver of the Assessments (page 16) (accessed July 2, XXII. FIFRA Review Requirements Photodegradation in Water Data 2008) http://www.epa.gov/oppfead1/ Under FIFRA section 25(a), EPA has Requirement Based on the Electronic trac/science/aggregate.pdf. submitted a draft of the proposed rule Absorption Spectra of the Pesticide 36. USEPA FIFRA SAP Meeting May to the Secretary of the Department of (Henry Jacoby). 2005: A Comparison of the Results of Agriculture and the appropriate 26. USEPA (August 5, 1991). Studies on Pesticides from 12– or 24– Congressional Committees. There were Memorandum: Revised Mutagenicity Month Dog Studies with Dog Studies of no comments in response to these Guideline and Requirement – Shorter Duration (accessed July 2, 2008) submissions. Explanation, from Kerry L. Dearfield, http://www.epa.gov/scipoly/sap/ Under FIFRA section 21(b) EPA Science Analysis and Coordination meetings/2005/may2/ submitted a draft of the proposed rule Branch. dogstudymay05.pdf. to the Secretary of Health and Human 27. USEPA (September 1993). 37. USEPA FIFRA SAP Meeting Services (HHS). Their comments on this Pesticide Reregistration Rejection Rate Minutes No. 2005–03: A Set of proposed rule included requests for (1) Analysis – Environmental Fate (EPA Scientific Issues Being Considered by clarification on the application of these 738–R–93–010). the Environmental Protection Agency new testing requirements to current 28. USEPA (February 7, 1996). Regarding: A Comparison of the Results registrants, (2) information about prions, Pesticide Registration (PR) Notice 96–1. of Studies on Pesticides from 12– or 24– (3) the possible effects of antimicrobial Tolerance Enforcement Methods — Month Dog Studies with Dog Studies of residues present in food on intestinal Independent Laboratory Validation by Shorter Duration (accessed June 30, flora, and (4) the potential for Petitioner. (accessed July 1, 2008) http:// 2008) http://www.epa.gov/scipoly/sap/ antimicrobial resistance. www.epa.gov/opppmsd1/PR_Notices/ meetings/2005/may5/ EPA agrees with HHS that both pr96–1.html. meetingminutesmay5_6_2005.pdf. current antimicrobial pesticide 29. USEPA Federal Insecticide, 38. USEPA (March 20, 2006). Length registrants and applicants seeking an Fungicide and Rodenticide Act (FIFRA) of Dog Toxicity Study(ies) that is antimicrobial registration should Scientific Advisory Panel (SAP) Meeting Appropriate for Chronic RfD understand the applicability of the of June 1997: A Set of Scientific Issues Determinations of Pesticide Chemicals. proposed data requirements, once

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00046 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59427

promulgated. Once effective, EPA regulatory action’’ because this action data requirements, and then gathered would use the promulgated data might raise novel legal or policy issues information on the price that requirements as the standard for arising out of legal mandates, the laboratories might charge to conduct reviewing new applications. These same President’s priorities, or the principles that study. To the extent possible, promulgated data requirements, once set forth in the Executive Order. several cost estimates were compiled for effective, would also be used during Accordingly, as a result of this OMB each study. The low and high cost Registration Review, when the Agency’s determination, EPA submitted this estimates provided by the various scientists prepare the publicly available proposed rulemaking to OMB for review laboratories were averaged to account documentation on the data needed under Executive Order 12866. Any for price variations related to differences during Registration Review to complete changes made in response to OMB in the assumptions about the study the needed risk assessments. comments have been documented in the performed (e.g., protocol, species used), EPA also agrees that the criteria for public docket for this rulemaking as and differences in the price charged by determining the efficacy of proposed required by section 6(a)(3)(E) of the different laboratories. anti-prion agents have not yet been Executive Order. EPA assumed that each data established. EPA has prepared an economic requirement would always be fulfilled Concerning HHS’s Center for analysis of the potential costs associated and therefore data would always need to Veterinary Medicine’s (CVM) comment with this proposed action, entitled be generated for each requirement. This on intestinal flora, EPA believes that the ‘‘Economic Analysis of the Proposed assumption could lead to an studies proposed in this rule for use in Change in Data Requirements for overestimate of the burden of the a pesticide risk assessment are Antimicrobial Pesticides.’’ It is noted proposal, because sometimes the data protective of human health. EPA has no that this analysis applies only to new are already available because the firm specific information on effects on antimicrobial pesticides submitted for generated it for their own use. In such antimicrobial residues that would not be registration, and to new uses of cases, the firm would simply need to captured by the required health effects currently registered antimicrobial submit those data to EPA, which studies. pesticides. For conducting its economic involves less burden and cost than HHS’s CVM is correct that this analysis, EPA considered a registration generating it. Some firms may have proposed rule does not address action as referring to an application for surrogate data that could be used, while potential antimicrobial resistance as a registration of a new product that others may qualify for a waiver. Some result of the use of a pesticide product. contains an active ingredient that is not firms may share the cost of generating While the Pesticide Program is aware of included in any currently registered the data. All of these would involve this issue, we have neither determined product, an application for a new lower costs than generating the data the extent of the problem nor how data product that includes the addition of a anew. requirements could be developed to use pattern that is not currently EPA then used historical data on address the issue. The Pesticide registered for one or more active antimicrobial pesticide registration Program will continue to monitor efforts ingredients contained in the product, actions that occurred from 2000 to 2005 such as those of the CODEX ad hoc and an amendment of a registration of to identify the entities that sought Intergovernmental Task Force on a product that includes the addition of pesticide registration actions in the past. Antimicrobial Resistance and the a use pattern that is not currently The data required for each registration Interagency Task Force on registered for one or more active action depends on several factors, Antimicrobial Resistance, on which ingredients contained in the product. including the type of registration action EPA is a participant (see http:// A copy of the economic analysis (Ref. (e.g., registration of a new active www.cdc.gov/drugresistance/ 44) can be found in the public docket ingredient food-use, registration of a actionplan/). The research being for this action, and is briefly new active ingredient nonfood-use, registration and amendments to conducted by the collaborating federal summarized here. registrations involving a major new use); agencies, which is primarily focused on In the proposed rule, EPA is: • scientific discipline (e.g., toxicology, antibiotics, may eventually form the Proposing newly codified data residue chemistry, human exposure), basis for the Pesticide Programs’ requirements, which are not currently and use pattern. The percentage of time approach to potential resistance as a established in part 161, but are routinely a particular test would be required was result of the use of pesticide products. considered in current practice. • estimated from this information. For the We have the authority to require studies Proposing changes to some of the new data requirements, the percentage on a case-by-case basis and to revise our existing data requirements such as a of time was estimated by EPA scientists, data requirements in the future, if change from conditionally-required to based on their past experience in the appropriate. required, a change in the number of test program and their understanding of the EPA requested that the SAP waive its species, or expanding the number of use need for and the use of the new data review of this proposal based on the patterns for which the test is required. • Proposing new data requirements, requirements. SAP’s 1997 review. The SAP waived its which have never been required or have The Agency prepared an industry review of this proposal on February 19, rarely been required on a case-by-case profile using the same historical data on 2008. basis, and have not been routinely pesticide registration actions to identify XXIII. Statutory and Executive Order considered during the Agency’s the companies involved in those Reviews evaluation of the data needed for the actions, and based it on public purpose of risk assessment. information gathered about those A. Executive Order 12866 • Proposing to eliminate the companies. EPA also used this industry Pursuant to Executive Order 12866, requirement for the chronic nonrodent profile to analyze the potential impacts entitled Regulatory Planning and study currently established in part 161. of the proposed rule on small Review (58 FR 51735, October 4, 1993), To calculate the potential costs businesses, the results of which are the Office of Management and Budget associated with this proposal, EPA first summarized in Unit XXIII.B below. (OMB) has determined that this identified the studies that would Overall the potential impact of this proposed rule is a ‘‘significant generate the data to fulfill the proposed proposal on businesses is small, and

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00047 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59428 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

therefore the Agency believes that a users is unlikely. On balance, the benefits from enhanced protection of negative effect on the availability of Agency believes that the costs of the human health and the environment. antimicrobial pesticide products to proposed rule are justified by the

TABLE 2.—TOTAL ANTIMICROBIAL INDUSTRY COST PER YEAR

Total Industry Cost per Year ($1000)

Baseline (BL) 11,080

Current Practices (CP) 11,726

Proposed Rule (PR) 14,961

Incremental Costs (PR – BL) 3,882

Newly Imposed Costs (PR-CP) 3,236

Thus, the difference between the costs are unknown. EPA will articulate rarely pesticide applicants or baseline (the existing data requirements the specific burden and costs associated registrants. that were codified in 1984) and the with each DCI pursuant to the Some of the small entities directly Agency’s current practices in requiring appropriate Information Collection regulated by this rulemaking are in the data is $646,000 annually. The Request (ICR) approvals under the pesticide and other agricultural difference between the proposed data Paperwork Reduction Act (PRA). chemical manufacturing industry sector requirements and current practices is (NAICS code 325320). Firms in this B. Regulatory Flexibility Act $3.2 million annually. The difference sector are considered small under the between the proposed data requirements Pursuant to section 605(b) of the RFA definition if they employ 500 or and the existing data requirements is Regulatory Flexibility Act (RFA), 5 USC fewer people. The economic analysis for $3.9 million annually. The average cost 601 et seq., the Agency hereby certifies this proposed rule specifies the NAICS per registration action of a new that this action will not have a code used for each of the firms antimicrobial active ingredient is significant adverse economic impact on analyzed. approximately $1 million to $4.5 a substantial number of small entities. As detailed in the Economic Analysis, million. It is noted that this analysis The factual basis for the Agency’s EPA estimates that 750 unique parent applies only to new antimicrobial determination is presented in the small companies constitute the total universe pesticides submitted for registration, entity impact analysis prepared as part of pesticide antimicrobial registrants. Of and to new uses of currently registered of the economic analysis for this these, based on the SBA definition of a antimicrobial pesticides. proposed rule (Ref. 44), which is small business and the available sales For existing chemicals, the proposed summarized in Unit XXIII.A., and a data for these firms, EPA estimates that part 158 subpart W data requirements copy of which is available in the docket 500, or approximately 67%, qualify as a would be relevant to the registration for this rulemaking. The following is a small business. The available review program which began to replace brief summary of the factual basis for antimicrobial pesticide registration data the reregistration program in 2006 as a this certification. for 2000–2005 indicates that only a means of systematically reviewing Under the RFA, small entities include small portion of the 500 registrants are existing registrations against the small businesses, small organizations, likely to be impacted by the proposed standards of FIFRA. Data needs and small governmental jurisdictions. regulation. Specifically, 64 firms with identified under registration review for For purposes of assessing the impacts of antimicrobial registrations would have existing chemicals must be imposed today’s proposed rule on small entities, incurred additional costs under the under the Agency’s Data Call-In (DCI) small entity is defined in accordance proposed rule. Of the 64 firms, EPA program. with the RFA as: (1) a small business as estimates that a total of 25 small EPA has not evaluated the potential defined by the Small Business pesticide registrants would have burden of the proposed data Administration’s (SBA) regulations at 13 incurred additional costs under the requirements on registrants of existing CFR 121.201, which is based on either proposed rule. chemicals in this proposal. However, the maximum number of employees or The impacts to small antimicrobial EPA anticipates that there will be on the sales for small businesses in each registrants are measured as the per firm additional costs associated with the industry sector, as defined by a 6–digit incremental cost, which is the proposed studies under Registration NAICS code; (2) a small governmental difference between the existing data Review. For each chemical, EPA will jurisdiction that is a government of a requirements in part 161 (the baseline) evaluate the specific need for additional city, county, town, school district or and those proposed in this rule. The data, including studies proposed today. special district with a population of less impact of the regulation is expressed as Stakeholders and the public have than 50,000; and (3) a small the proportion of the average annual per opportunities for input, consultation organization that is any not-for-profit firm incremental costs to the average and involvement concerning individual enterprise which is independently annual firm sales. pesticide cases throughout the owned and operated and is not The Agency’s analysis of impacts on registration review process. Although dominant in its field. EPA has small businesses indicates that: EPA has identified the schedule for determined that this rulemaking does • About 25 (5%) of the 500 small firms which chemicals will be reviewed over not impact any small governmental subject to the proposal are likely to the next few years, the evaluation of jurisdictions or any small not-for-profit experience some impact (greater than data needs has not been done. Thus, the enterprise because these entities are 0%).

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00048 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59429

• About 22 (4.4%) of the 500 small 1. The data submission activities section at the beginning of this firms are likely to experience an associated with the establishment of a document for where to submit economic impact of 1% or more of gross tolerance are currently approved under comments to EPA. sales. OMB Control No. 2070–0024 (EPA ICR You may also submit a copy of your • About 14 (2.8%) of the 500 small No. 0597); comments on the ICR directly to OMB. firms are likely to experience an 2. The data submission activities Comments to OMB should be sent to the economic impact of 3% or more of gross associated with the application for a Office of Information and Regulatory sales. new or amended registration of a Affairs, Office of Management and Based on the Agency’s small business pesticide are currently approved under Budget (OMB), 725 17th Street, NW, impact analysis, the Agency does not OMB Control No. 2070–0060 (EPA ICR Washington, DC 20503, Attention: Desk anticipate that the additional costs to No. 0277); Office for EPA. Since OMB is required industry resulting from this proposed 3. The data submission activities to make a decision concerning the ICR rule will cause a significant adverse associated with the generation of data between 30 and 60 days after October 8, economic impact on a substantial for reregistration are currently approved 2008, a comment to OMB is best assured number of small entities because the under OMB Control No. 2070–0107 of having its full effect if OMB receives additional costs are a small share of (EPA ICR No. 1504); and it by November 7, 2008. gross revenues for most firms and less 4. The data submission activities In the final rule, the Agency will than 5% of small firms are likely to associated with the generation of data address any comments received experience some impact. for special review or registration review regarding the information collection EPA is particularly interested in are currently approved under OMB requirements contained in this proposal. receiving comment from small Control No. 2070–0057 (EPA ICR No. In addition, after the ICR for the final businesses as to the benefits, costs and 0922). rule is approved, EPA will incorporate impacts of this rule. Any comments These program activities are an the increased burden into the existing should be submitted to the Agency in integral part of the Agency pesticide ICRs as appropriate. the manner specified under ADDRESSES. program and the corresponding ICRs are regularly renewed every three years as D. Unfunded Mandates Reform Act C. Paperwork Reduction Act required by the PRA. The total Under Title II of the Unfunded The information collection estimated average annual public Mandates Reform Act of 1995 (UMRA) requirements contained in this proposed reporting burden currently approved by (Public Law 104– 4), EPA has rule have been submitted for approval to OMB for these various activities range determined that this action does not the Office of Management and Budget from 8 hours to approximately 3,000 contain a Federal mandate that may (OMB) under the Paperwork Reduction hours per respondent, depending on the result in expenditures of $100 million or Act (PRA), 44 U.S.C. 3501 et seq. EPA activity and other factors surrounding more for State, local, and tribal has prepared a new Information the particular pesticide product. governments, in the aggregate, or the Collection Request (ICR) document In the new ICR for this proposed rule, private sector in any one year. As identified by EPA ICR No. 2318.01, a which is based on the Economic described in this document, the copy of which has also been placed in Analysis (Ref. 44), EPA estimates that incremental costs for the proposed part the docket for this proposed rule. (Ref. the typical current annual paperwork 158 subpart W data requirement 45). burden for registrants per antimicrobial changes for antimicrobial pesticides is Under the PRA, ‘‘burden’’ is defined pesticide registration is 194 burden estimated at nearly $3.9 million per year at 5 CFR 1320.3(b). In addition, an hours and $12,631. This represents the for the private sector, which is below agency may not conduct or sponsor, and baseline antimicrobial pesticide the $100 million threshold. Since State, a person is not required to respond to registration burden and costs. When local, and tribal governments are rarely an information collection request unless considering the potential increase in pesticide applicants, the proposed rule it displays a currently valid OMB this estimated annual burden and cost is not expected to significantly or control number, or is otherwise required resulting from the new data uniquely affect small governments. to submit the specific information by a requirements in this proposed rule, the Accordingly, this action is not subject to statute. The OMB control numbers for Agency estimated the incremental the requirements of sections 202 and certain EPA regulations in 40 CFR, after burden and cost to be 35% of the 205 of UMRA. appearing in the preamble of the final baseline burden and costs, i.e., 68 rule, are listed in 40 CFR part 9 and, if burden hours and $4,421. Assuming an E. Executive Order 13132 applicable, included with the related annual number of 15 antimicrobial Pursuant to Executive Order 13132, collection instrument (e.g., form or pesticide registrations, the total annual entitled Federalism (64 FR 43255, survey). registrant paperwork burden and costs August 10, 1999), EPA has determined The information collection activities for antimicrobial pesticide registrations that this proposed rule does not have related to the submission of data to EPA are estimated to be approximately 3,929 ‘‘federalism implications,’’ because it in order to register, amend or retain a hours and $255,773.25, of which 1,019 will not have substantial direct effects new or existing pesticide product or hours and $66,150 represent burden on the states, on the relationship obtain a tolerance for that product are related to new data requirements, and between the national government and already approved by OMB under the $158.25 represents estimated delivery the states, or on the distribution of PRA. As such, this ICR only addresses costs. power and responsibilities among the the proposed changes to the data Any comments on the Agency’s need various levels of government, as requirements that impact the for this information, the accuracy of the specified in the Order. As indicated information collection activities related provided burden estimates, and any above, instances where a state is a to antimicrobial pesticides. The suggested methods for minimizing registrant are extremely rare. Therefore, procedures for submitting data to EPA respondent burden, should be directed this proposed rule may seldom affect a under FIFRA and the FFDCA are not to the docket for this proposed rule, state government. Thus, Executive changed in this proposal, and are under Docket ID number EPA–HQ– Order 13132 does not apply to this already approved by OMB as follows: OPP–2008–0110. See ADDRESSES proposed rule. In the spirit of the Order,

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00049 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59430 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

and consistent with EPA policy to Minority Populations and Low-Income Distribution, or Use’’ (66 FR 28355, May promote communications between the Populations (59 FR 7629, February 16, 22, 2001) because it is not likely to have Agency and State and local 1994), the Agency does not need to any adverse effect on the supply, governments, EPA specifically solicits consider environmental justice-related distribution, or use of energy. comment on this proposed rule from issues. Lists of Subjects in 40 CFR Part 158 State and local officials. I. National Technology Transfer and Environmental protection, F. Executive Order 13175 Advancement Act Administrative practice and procedure, As required by Executive Order Section 12(d) of the National Agricultural commodities, Pesticides 13175, entitled Consultation and Technology Transfer and Advancement and pests, Reporting and record keeping Coordination with Indian Tribal Act of 1995 (NTTAA), 15 U.S.C. 272 requirements. Governments (65 FR 67249, November note) directs EPA to use voluntary Lists of Subjects in 40 CFR Part 161 6, 2000), EPA has determined that this consensus standards in its regulatory proposed rule does not have tribal activities unless to do so would be Environmental protection, implications because it will not have inconsistent with applicable law or Administrative practice and procedure, substantial direct effects on tribal impractical. Voluntary consensus Agricultural commodities, Pesticides governments, on the relationship standards are technical standards (e.g., and pests, Reporting and record keeping between the Federal government and materials specifications, test methods, requirements. the Indian tribes, or on the distribution sampling procedures, etc.) that are of power and responsibilities between developed or adopted by voluntary Dated: September 24, 2008. the Federal government and Indian consensus standards bodies. NTTAA Stephen L. Johnson, tribes, as specified in the Order. As directs EPA to provide Congress, Administrator. indicated above, at present, no tribal through OMB, explanations when the Therefore, it is proposed that 40 CFR governments hold, or have applied for, Agency decides not to use available and part 158 and part 161 be amended as a pesticide registration. Thus, Executive applicable voluntary consensus follows: Order 13175 does not apply to this standards. This regulation proposes the 1. The authority citation for part 158 proposed rule. In the spirit of the Order, types of data to be required to support continues to read as follows: and consistent with EPA policy to antimicrobial pesticide registration but promote communications between the Authority: 7 U.S.C. 136–136y and 21 does not propose to require specific U.S.C. 346a. Agency and State and local methods or standards to generate those governments, EPA specifically solicits data. 2. Section 158.1(c)(4) is revised to comment on this proposed rule from This proposed regulation does not read as follows: tribal officials. impose any technical standards that § 158.1 Purpose and scope. G. Executive Order 13045 would require Agency consideration of voluntary consensus standards. The * * * * * This section is not subject to Agency invites comment on its (c) * * * Executive Order 13045, entitled conclusion regarding the applicability of (4) Antimicrobial pesticides. Subparts Protection of Children from voluntary consensus standards to this A, B, C, D, and W apply to antimicrobial Environmental Health Risks and Safety rulemaking. pesticides. Risks (62 FR 19885, April 23, 1997) 3. Section 158.100 is amended by because it does not propose an J. Executive Order 12630 revising the heading of paragraph (a); by environmental standard that is intended EPA has complied with Executive revising paragraph (b); by redesignating to have a negatively disproportionate Order 12630, entitled Governmental paragraph (c) as paragraph (e); and by effect on children. To the contrary, this Actions and Interference with adding new paragraphs (c) and (d) to action will provide added protection for Constitutionally Protected Property read as follows: children from pesticide risk. The Rights (53 FR 8859, March 15, 1988), by § 158.100 Pesticide use patterns. proposed data requirements are examining the takings implications of intended to address risks that, if not this rule in accordance with the (a). General use patterns for addressed, could have a ‘‘Attorney General’s Supplemental conventional, biochemical, and disproportionate negative impact on Guidelines for the Evaluation of Risk microbial pesticides. *** children. EPA will use the data and and Avoidance of Unanticipated (b) Pesticide use site index for information obtained by this proposed Takings’’ issued under the Executive conventional, biochemical, and rule to carry out its mandate under Order. microbial pesticides. The Pesticide Use FFDCA to give special attention to the Site Index for Conventional, risks of pesticides to sensitive K. Executive Order 12988 Biochemical, and Microbial Pesticides is subpopulations, especially infants and In issuing this rule, EPA has taken the a comprehensive list of specific children. necessary steps to eliminate drafting pesticide use sites. The index is errors and ambiguity, minimize alphabetized separately by site for all H. Executive Order 12898 potential litigation, and provide a clear agricultural and all nonagricultural This proposed rule does not have an legal standard for affected conduct, as uses. The Pesticide Use Site Index adverse impact on the environmental required by section 3 of Executive Order associates each pesticide use site with and health conditions in low-income 12988, entitled Civil Justice Reform (61 one or more of the 12 general use and minority communities because this FR 4729, February 7, 1996). patterns. It may be used in conjunction proposed rule only impacts entities that with the data tables to determine the intend to register or currently hold a L. Executive Order 13211 applicability of data requirements to registration for an antimicrobial This rule is not subject to Executive specific uses. The Pesticide Use Site pesticide. Therefore, under Executive Order 13211, entitled ‘‘Actions Index for Conventional, Biochemical, Order 12898, entitled Federal Actions to concerning Regulations that and Microbial Pesticides, which will be Address Environmental Justice in Significantly Affect Energy Supply, updated periodically, is available from

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00050 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59431

the Agency or may be obtained from the section 409. EPA will apply this subpart (1) Disinfectant means a substance Agency’s website at http:// to all products intended for an that destroys or eliminates a specific www.epa.gov/pesticides. antimicrobial use, purpose or function; species of infectious or other public (c) Antimicrobial pesticide use the exclusion in FIFRA section health microorganism, but not patterns. The general use patterns for 2(mm)(1)(B) does not exclude products necessarily bacterial spores, in the antimicrobial pesticides are described in from the data requirements of this inanimate environment. § 158.2201. subpart. (2) Fungicide means a substance that (d) Pesticide use site index for (b) A product that bears both destroys fungi (including yeasts) and antimicrobial pesticides. The Pesticide antimicrobial and non-antimicrobial fungal spores pathogenic to man or Use Site Index for Antimicrobial uses or claims is subject to the data other animals in the inanimate Pesticides is a comprehensive list of requirements for pesticides in subparts environment. specific antimicrobial use sites. The C – O, and U or V of this part with (3) Microbiological water purifier index is alphabetized by antimicrobial respect to its non-antimicrobial uses and means any unit, water treatment use sites, and associates each claims, and to the requirements of this product or system that removes, kills or antimicrobial use site with one or more subpart W with respect to its inactivates all types of disease-causing of the antimicrobial use patterns. It may antimicrobial uses and claims. microorganisms from the water, be used in conjunction with the data (c) A wood preservative, including a including bacteria, viruses and tables to determine the applicability of product that is intended to prevent protozoan cysts, so as to render the data requirements to specific uses. The wood degradation problems due to treated water safe for drinking. Pesticide Use Site Index for fungal rot or decay, sapstain, or molds. (4) Sanitizer means a substance that Antimicrobial Pesticides, which will be (d) An antifoulant, including a reduces the bacterial population in the updated periodically, is available from product that is intended to kill or repel inanimate environment by significant the Agency or may be obtained from the organisms that can attach to underwater numbers, but does not destroy or Agency’s website at http:// surfaces, such as boat bottoms. eliminate all bacteria or other microorganisms. www.epa.gov/pesticides/regulating/ § 158.2201 Antimicrobial use patterns. usesite/. (5) Sterilant means a substance that (e) * * * (a) Antimicrobial use patterns. The 12 destroys or eliminates all forms of general use patterns used in the data microbial life in the inanimate § 158.400 [Amended] tables in this subpart are: environment, including all forms of 4. The table in § 158.400(d) is (1) Agricultural premises and vegetative bacteria, bacterial spores, amended by removing the category equipment. fungi, fungal spores, and viruses. For ‘‘Efficacy of antimicrobial agents’’ and (2) Food-handling/storage purposes of this subpart, ‘‘sporicide’’ all of the entries under that category. establishments, premises and and ‘‘sterilant’’ are synonymous. 5. Part 158 is amended by adding equipment. (6) Tuberculocide means a substance subpart W to read as follows: (3) Commercial, institutional and that destroys or irreversibly inactivates industrial premises and equipment. tubercle bacilli in the inanimate Subpart W—Antimicrobial Pesticide (4) Residential and public access environment. Data Requirements premises. (7) Virucide means a substance that (5) Medical premises and equipment. destroys or inactivates viruses in the Sec (6) Human drinking water systems. inanimate environment. § 158.2200 Applicability. (7) Materials preservatives. (b) Public health claim. An § 158.2201 Antimicrobial use patterns. (8) Industrial processes and water § 158.2203 Definitions. antimicrobial pesticide is considered to systems. make a public health claim if the § 158.2210 Product chemistry. (9) Antifoulant paints and coatings. pesticide product bears a claim to § 158.2220 Product performance. (10) Wood preservatives. § 158.2230 Toxicology data. (11) Swimming pools. control pest microorganisms that pose a § 158.2240 Nontarget organisms. (12) Aquatic areas. threat to human health, and whose § 158.2250 Nontarget plant protection. (b) Use site index. The Antimicrobial presence cannot readily be observed by § 158.2260 Applicator exposure. Use Site Index is a comprehensive list the user, including but not limited to, § 158.2270 Post-application exposure. microorganisms infectious to man in § 158.2280 Environmental fate. of specific antimicrobial use sites. The § 158.2290 Residue chemistry. Index associates antimicrobial use sites any area of the inanimate environment. with one or more of the 12 antimicrobial A product makes a public health claim Subpart W—Antimicrobial Pesticide use patterns. It is to be used in if one or more of the following apply: Data Requirements conjunction with the data tables in this (1) A claim is made for control of subpart to determine the applicability of specific microorganisms or classes of § 158.2200 Applicability. data requirements to specific uses. The microorganisms that are directly or Subpart W establishes data Antimicrobial Pesticide Use Site Index, indirectly infectious or pathogenic to requirements for any pesticide product which will be updated periodically, is man (or both man and animals). that is: available from the Agency or may be Examples of specific microorganisms (a) A pesticide that is intended for use obtained from the Agency’s website at include, but are not limited to, as an ‘‘antimicrobial pesticide’’ within http://www.epa.gov/pesticides/ Mycobacterium tuberculosis, the meaning of FIFRA section regulating/usesite/. Pseudomonas aeruginosa, Eschericha 2(mm)(1)(A), regardless of whether it (c) An applicant unsure of the correct coli (E. coli), human immunodeficiency also meets the criterion of FIFRA use pattern(s) for his product should virus (HIV), Streptococcus, and section 2(mm)(1)(B). That criterion consult the Agency. Staphylococcus aureus. Claims for excludes from the definition any control of microorganisms infectious or antimicrobial product that is intended § 158.2203 Definitions. pathogenic only to animals (such as for a food-use requiring a tolerance or (a) Definitions. The following terms canine distemper virus or hog cholera exemption under FFDCA section 408 or are defined for the purposes of this virus) are not considered public health a food additive regulation under FFDCA subpart: claims.

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00051 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59432 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

(2) A claim is made for the pesticide public health microorganism and there product registered or proposed for product as a sterilant, disinfectant, is no other functional purpose for the registration. virucide, sanitizer, or tuberculocide ingredient in the product; or (2) Product performance data for each regardless of the site of use of the (ii) The pesticide product is similar in product that bears a public health product, and regardless of whether composition to a registered pesticide claim. Each product that bears a public specific microorganisms are identified. product that makes explicit health claim, as described in (3) A claim is made for the pesticide antimicrobial public health claims. § 158.2203(b), must be supported by product as a fungicide against fungi § 158.2210 Product chemistry. product performance data, as listed in infectious or pathogenic to man, or the the table in this paragraph. Product product does not clearly state that it is The product chemistry data performance data must be submitted intended for use only against non-public requirements of subpart D of this part with the application for registration or health fungi. apply to antimicrobial products covered amended registration. (4) A claim is made for the pesticide by this subpart. (3) Determination of data product as a microbiological water purifier or microbial purification § 158.2220 Product performance. requirements. Subpart B of this part and system. (a) General. (1) Product performance § 158.2201 describe how to use the table (5) A non-specific claim is made that requirement for all antimicrobial in paragraph (c) of this section to the pesticide product will beneficially pesticides. Each applicant must ensure determine the product performance data impact or affect public health at the site through testing that his product is requirements for antimicrobial pesticide of use or in the environment in which efficacious when used in accordance products. applied (such as a ‘sanitary’ claim), and: with label directions and commonly (b) Key. R = Required; EP = End-use (i) The pesticide product contains one accepted pest control practices. The product; or more ingredients that, under the Agency may require, on a case-by-case (c) Table. The following table shows criteria in 40 CFR 153.125(a), is an basis, submission of product the data requirements for product active ingredient with respect to a performance data for any pesticide performance.

TABLE — ANTIMICROBIAL PRODUCT PERFORMANCE DATA REQUIREMENTS

Guideline Number Data Requirement All Use Patterns Test Substance

91–2 Products for use on hard sur- R EP faces

91–3 Products requiring confirmatory R EP data

91–4 Products for use on fabrics and R EP textiles

91–5 Air sanitizers R EP

91–7 Products for control of microbial R EP pests associated with human and animal wastes

91–8 Products for treating water sys- R EP tems

§ 158.2230 Toxicology data. includes those uses which are likely to (vii) Outdoor aquatic uses in lakes, (a) General. Subpart B of this part and result in human exposure over a rivers or streams which have the § 158.2201 describe how to use the table considerable portion of the human potential to contaminate potable water. in paragraph (d) of this section to lifespan, and which are significant in (viii) Wood preservatives. determine the toxicology data terms of frequency, duration, or (ix) Metalworking fluids. requirements for an antimicrobial magnitude of exposure, i.e., uses for pesticide product. Notes that apply to which there is an expectation of high, (2) Low human exposure nonfood and an individual test including specific prolonged, or repeated exposure. High low human exposure indirect food uses. conditions, qualifications, or exceptions human exposure uses of antimicrobials Generally, low exposure uses are those are listed in paragraph (e) of this include but are not limited to: not listed in paragraph (b)(1) of this section. (i) Any use which requires a tolerance section as high exposure uses. (b) Uses. The applicant for registration or tolerance exemption (except for (3) Tiering of data requirements. must first determine whether the use is indirect food uses requiring a tolerance Applicants for registration of a high human exposure use or a low or tolerance exemption in which antimicrobials may perform tests in a human exposure use. If an applicant is residues are less than 200 ppb). tiered fashion. After the initially not sure if a specific use is a high (ii) Indirect food uses with residues required tests are conducted, additional human exposure or a low human equal to or greater than 200 ppb. testing may be required if results of the exposure use, the applicant should (iii) Use in human or animal drinking initial tests trigger the need for consult the Agency. water. additional data. Conditions that trigger (1) High human exposure uses. For (iv) Fruit and vegetable rinses. the need for additional data are given in the purpose of determining data (v) Egg washes. the test notes in paragraph (e) of this requirements, high human exposure (vi) Swimming pools. section.

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00052 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59433

(c) Key. R = Required; CR = TEP = Typical end-use product; PAI = (d) Table. The following table shows Conditionally required; NR = Not Pure active ingredient; PAIRA = Pure the data requirements for toxicology. required; MP = Manufacturing-use active ingredient, radiolabeled; Choice = The test notes appear in paragraph (e) of product; EP = End-use product; TGAI = choice of several test substances this section. Technical grade of the active ingredient; depending on studies required.

TABLE — ANTIMICROBIAL TOXICOLOGY DATA REQUIREMENTS

Use Pattern Test Substance to Support Low Guideline Number Data Requirement High Human Test Note No. Human20Exposure Exposure MP EP Uses Uses

Acute Testing

870.1100 Acute oral toxicity - rat R R MP and EP and 1, 2 TGAI TGAI

870.1200 Acute dermal toxicity R R MP and EP and 1, 2, 3 TGAI TGAI

870.1300 Acute inhalation toxicity - rat R R MP and EP and 4 TGAI TGAI

870.2400 Primary eye irritation - rabbit R R MP and EP and 1, 2, 3 TGAI TGAI

870.2500 Primary dermal irritation R R MP and EP and 1, 2, 3 TGAI TGAI

870.2600 Dermal sensitization R R MP and EP and 1, 2, 3, 5 TGAI TGAI

870.6200 Acute neurotoxicity - rat R CR TGAI TGAI 6

Subchronic Testing

870.3100 90–Day oral toxicity - rodent R R TGAI TGAI 7, 8, 9, 15

870.3150 90–Day oral toxicity - nonrodent R CR TGAI TGAI 7, 10, 11, 15

870.3250 21/28–Day dermal toxicity CR CR TGAI EP and 12, 13 TGAI

870.2500 90–Day dermal toxicity CR CR TGAI EP and 7, 13, 14, 15 TGAI

870.3465 90–Day inhalation - toxicity - rat CR CR TGAI TGAI 7, 15, 16, 17

870.6200 90–Day neurotoxicity - rat R CR TGAI TGAI 6, 8

Chronic Testing

870.4100 Chronic oral toxicity - rodent R CR TGAI TGAI 18, 19, 20

870.4200 Carcinogenicity - two rodent species R CR TGAI TGAI 19, 21, 22 - rat and mouse preferred

Developmental Toxicity and Reproduction

870.3700 Prenatal developmental toxicity - rat R R TGAI TGAI 23, 24, 25, 26 and rabbit preferred

870.3800 Reproduction and fertility effects R R TGAI TGAI 26, 27, 28, 29

870.6300 Developmental neurotoxicity CR CR TGAI TGAI 28, 29, 30

Mutagenicity

870.5100 Reverse mutation assay R R TGAI TGAI 31, 32

870.5300 In vitro mammalian gene mutation R R TGAI TGAI 31, 33 870.5375

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00053 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59434 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

TABLE — ANTIMICROBIAL TOXICOLOGY DATA REQUIREMENTS—Continued

Use Pattern Test Substance to Support Low Guideline Number Data Requirement High Human Test Note No. Human20Exposure Exposure MP EP Uses Uses

870.5380 In vivo cytogenetics R R TGAI TGAI 31, 34 870.5385 870.5395

Special Testing

870.7485 Metabolism and pharmacokinetics R CR PAI or PAI or 35 PAIRA PAIRA

870.7200 Companion animal safety CR CR NR Choice 36

870.7600 Dermal penetration CR CR Choice Choice 37

870.7800 Immunotoxicity R R TGAI TGAI --

(e) Test notes. The following test encourage the applicant to conduct a 90–day available information about the toxic effects notes apply to the data requirements in range finding study for the purposes of dose of the product or its components. the table to paragraph (d) of this section: selection for the mouse carcinogenicity study 14. Data are required if the use pattern is 1. Not required if test material is a gas or to achieve adequate dosing and an acceptable such that the dermal route would be the highly volatile liquid. study. The applicant is also encouraged to major route of exposure or if the active 2. For the six acute toxicity studies consult with the Agency on the results of the ingredient of the product is known or conducted with the end-use product, the test 90–day mouse study prior to conducting the expected to be metabolized differently by the must be conducted using the product as carcinogenicity study. dermal route of exposure than by the oral formulated for sale and distribution. 10. A 1–year non-rodent study (i.e., 1–year route, and a metabolite of the active However, if the end-use product is labeled dog study) may be required if the Agency ingredient is the toxic moiety. that the product is to be diluted for use, the finds that a pesticide chemical is highly 15. A 90–day oral toxicity test is not applicant may also conduct certain studies bioaccumulating and is eliminated slowly. required for heating, ventilation, air using the highest diluted concentration (i.e. Thus it does not achieve steady state or conditioning, and refrigeration systems the least diluted product) permitted by the sufficient tissue concentrations to elicit an (collectively referred to as HVAC), and two labeling. The end-use dilution testing is in effect during a 90–day study. EPA may 90–day toxicity tests, one by the dermal route addition to the as- formulated-for-sale testing require the appropriate tier II metabolism and and one by the inhalation route are required. and used only for labeling purposes. pharmacokinetic studies to evaluate more 16. Data are required if there is the Consultation with the Agency is highly precisely bioavailability, half life, and steady suggested to assure that the appropriate likelihood of significant repeated inhalation state to determine if a longer duration dog exposure to the pesticide as a gas, vapor, or product and any appropriate dilutions are toxicity study is needed. tested. aerosol. 11. For low human exposure uses, data are 17. Based on estimates of the magnitude 3. Not required if test material is corrosive required if any of the following criteria are and duration of human exposure, studies of to skin or has pH less than 2 or greater than met: shorter duration, e.g., 21– or 28–days, may be 11.5. i. The use of the pesticide is likely to result sufficient to satisfy this requirement. 4. Data are required when the product in repeated human exposure over a limited consists of, or under conditions of use will Applicants for registration may consult with portion of the human lifespan, as determined result in, a respirable material (e.g., gas, the Agency to determine whether studies of by the Agency. vapor, aerosol or particulates). shorter duration would meet this ii. The use is an indirect food use (less than 5. Data are required if repeated dermal requirement. exposure is likely to occur under conditions 200 ppb). 12. Data are required if the intended use of 18. Based on the positive results of the of use. acute and/or 90–day neurotoxicity studies, or 6. For low exposure uses, data are required the antimicrobial pesticide product is expected to result in human exposure to the on other data indicating neurotoxicity, a if the neurotoxicity screen in the 90–day oral chronic/neurotoxicity study (i.e. a chronic rodent study or other data indicate product, and the three following conditions are met: study with additional neurotoxicity neurotoxicity. evaluations) may be required to provide 7. The 90–day dermal toxicity study or 90– i. Human exposure is via skin contact. ii. Expected human exposure is not information about potential neurotoxic day inhalation toxicity study may be effects from long-term exposures. substituted for the 90–day oral toxicity study purposeful, and is over a limited portion of 19. Studies which are designed to if the Agency determines that dermal or the human lifespan; however, as determined simultaneously fulfill the requirements of inhalation exposure is a major route of by EPA, the exposure is significant in terms exposure. of the frequency of exposure, magnitude of both the chronic oral and carcinogenicity 8. All 90–day subchronic studies in the exposure, or the duration of exposure. studies (i.e., a combined study) may be rodent can be designed to simultaneously iii. Data from a subchronic 90–day dermal conducted. fulfill the requirements of the 90–day toxicity study are not available and the 90– 20. For low exposure, data are required if neurotoxicity study by adding separate day dermal toxicity study has not been either of the following criteria are met: groups of animals for testing. triggered. i. The use of the pesticide is likely to result 9. The 90–day study is required in the 13. EP testing is required if the product or in repeated human exposure over a limited rodent for hazard characterization (possibly any component of the product may increase portion of the human lifespan, as determined endpoint selection) and dose-setting for the dermal absorption of the active ingredient(s) by the Agency, or chronic/carcinogenicity study. It is not or increase toxic or pharmacologic effects, as ii. The use requires that a tolerance or a required in the mouse, but the Agency would determined by testing the TGAI or based on tolerance exemption be established.

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00054 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59435

21. For low exposure, data are required if ii. The pesticide causes treatment-related in paragraph (e) of this section to any of the following criteria, as determined neurological effects in developing animals, determine the terrestrial and aquatic by the Agency, are met: following pre- or post-natal exposure (i.e., nontarget organisms and nontarget plant i. The use of the pesticide is likely to result nervous system malformations or protection data requirements for a in significant human exposure over a neuropathy, brain weight changes in considerable portion of the human life span offspring, functional or behavioral changes in particular antimicrobial pesticide which is significant in terms of frequency the offspring). product. Notes that apply to an time, duration, and/or magnitude of iii. The pesticide elicits a causative individual test including specific exposure. association between exposures and adverse conditions, qualifications, or exceptions ii. The use requires that a tolerance or a neurological effects in human are listed in paragraph (f) of this section. tolerance exemption be established. epidemiological studies. (1) Terrestrial and aquatic nontarget iii. The active ingredient, metabolite, iv. The pesticide evokes a mechanism that organism data are required to support degradate, or impurity is associated with adverse effects on the the registration of most end-use and A. is structurally related to a recognized development of the nervous system (i.e., manufacturing-use antimicrobial carcinogen, structure-activity-relationship (SAR) to products. B. causes mutagenic effects as known neurotoxicants, altered neuroreceptor demonstrated by in vitro or in vivo testing, or or neurotransmitter responses). (2) Data are generally not required to C. produces a morphologic effect in any 31. To enhance the weight-of-evidence support end-use products of a gas, organ (e.g., hyperplasia, metaplasia) in determination for the pesticide’s highly volatile liquid, highly reactive subchronic studies that may lead to a mutagenicity, the Agency requires solid, or a highly corrosive material. neoplastic change. submission of other mutagenicity test results, (3) If the Agency determines that the 22. If the requirement for a carcinogenicity besides those specifically listed in this table, transformation products of the study in any species is modified or waived that may have been performed for other parentcompound are more toxic, for any reason, then a subchronic 90–day oral endpoints that may be predictive of persistent, bioaccumulative, or have study in the same species may be required. mutagenicity. A reference list of all studies been shown to cause adverse effects in 23. Testing in two species is required for and papers known to the applicant mammalian or aquatic reproductive concerning the mutagenicity of the test all uses. studies, then data on those 24. The oral route, by oral intubation, is chemical must be submitted with the preferred, unless the chemical or physical required studies. transformation products are required to properties of the test substance, or the pattern 32. Testing in Salmonella and E. coli may support registration. of exposure, suggest a more appropriate route be acceptable, if the testing can be conducted (4) For wood preservatives, the of exposure. at high enough levels, as determined by the Agency may require data on both the 25. Additional testing by other routes of Agency. If the testing cannot be conducted at parent compound, which is exposure may be required if the pesticide is high enough levels, then the applicant must incorporated into wood, and on determined to be a prenatal developmental consult with the Agency to determine other transformation/degradation products toxicant after oral dosing. needed mutagenicity testing. which occur in wood post-treatment or 26. The developmental toxicity study in 33. For the in vitro mammalian gene occur as dislodgeable residues (such as rodents may be combined with the two- mutation study, there is a choice of assays using either mouse lymphoma L5178Y cell hand contact with treated wood) or generation reproduction study in rodents by leachate residues (such as from soil or using a second mating of the parental thymidine kinase (tk) gene locus, maximizing animals in either generation. Protocols must assay conditions for small colony expression water contact with treated wood). be approved by the Agency prior to the and detection; Chinese hamster ovary (CHO) (b) Low environmental exposures. For initiation of the study. Details for developing or Chinese hamster lung fibroblast (v79) the purpose of determining data protocols are available from the Agency. cells, hypoxanthine-guanine phosphoribosyl requirements, the low environmental 27. A two-generation reproduction study is transferase (hgprt) gene locus, accompanied exposure grouping of use patterns required. by an appropriate in vitro test for includes the following use patterns or 28. An information-based approach to clastogenicity; or CHO cells strains AS52, partial use patterns: testing is preferred, which utilizes the best xanthine-guanine phosphoribosyl transferase (1) Agricultural premises and available knowledge on the chemical (hazard, (xprt) gene locus. equipment. pharmacokinetic, or mechanistic data) to 34. There is a choice of assays, but initial (2) Food-handling/storage determine whether a standard guideline consideration should be given to the rodent establishments, premises, and study, an enhanced guideline study, or an bone marrow assay. The micronucleus rodent bone marrow assay is preferred; the rodent equipment. alternative study should be conducted to (3) Commercial, institutional and assess potential hazard to the developing bone marrow assays using metaphase animal, or in some cases to support a waiver analysis (aberrations) are acceptable. industrial premises and equipment. for such testing. Applicants must submit any 35. For low exposure, these data are (4) Residential and public access alternative proposed testing protocols and required when chronic or carcinogenicity premises. supporting scientific rationale to the Agency. studies are also required. These data may be (5) Medical premises and equipment. Protocols must be approved by the Agency required if significant adverse effects are seen (6) Human drinking water systems. prior to the initiation of the study. Details for in available toxicology studies and these (7) Materials preservatives. developing protocols are available from the effects can be further elucidated by (8) Swimming pools. Agency. metabolism studies. (9) Recirculating industrial processes 29. The use of a combined two-generation 36. These data may be required if the and water systems in which the treated reproduction/developmental neurotoxicity product’s use will result in exposure to water is re-used repeatedly within the study that utilizes the two-generation domestic animals through, but not limited to, system. reproduction study in rodents as a basic direct application. (c) High environmental exposures. For protocol for the addition of other endpoints 37. A risk assessment assuming that dermal the purposes of determining data or functional assessments in the immature absorption is equal to oral absorption must be requirements, the high environmental performed to determine if the dermal animal is encouraged. exposure grouping of use patterns 30. A DNT study is required using a penetration study is required, and to identify weight-of-evidence approach when: the doses and duration of exposure for which includes the following use patterns or i. The pesticide causes treatment-related dermal absorption is to be quantified. partial use patterns: neurological effects in adult animal studies (1) Once-through industrial processes (i.e, clinical signs of neurotoxicity, § 158.2240 Nontarget organisms. and water systems in which the water neuropathology, functional or behavioral (a) General. Subpart B of this part and is not re-used, and is released after a effects). § 158.2201 describe how to use the table single cycle through the system.

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00055 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59436 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

(2) Antifoulant paints and coatings. NR = Not required; TGAI = Technical (e) Table. The following table shows (3) Wood preservatives. grade of the active ingredient; TEP = the data requirements for nontarget (4) Aquatic areas. Typical end-use product; PAIRA = Pure organisms. The test notes appear in (d) Key. MP = Manufacturing use active ingredient radiolabeled; a.i. = paragraph (f) of this section. product; EP = End use product; R = active ingredient. Required; CR = Conditionally required;

TABLE — ANTIMICROBIAL NONTARGET ORGANISM DATA REQUIREMENTS

Use Pattern Test Substance to Support High Environmental Exposure Guideline Data Require- Low Envi- Industrial Test Note Number ment ronmental Processes and Antifoulant No. Exposure Water Sys- Coatings Wood Pre- Aquatic MP EP tems(Once- and Paints servatives Areas Through)

Tier One Testing

850.2100 Acute avian oral R R R R R TGAI TGAI 1 toxicity

850.1010 Acute fresh- R R R R R TGAI TGAI 2 water inverte- brates toxicity

850.1075 Acute fresh- R R R R R TGAI TGAI 3 water fish tox- icity

Higher Tier Testing

Avian Testing

850.2200 Avian dietary CR CR CR CR R TGAI TGAI 4, 5 toxicity

850.2300 Avian reproduc- CR CR CR CR R TGAI TGAI 1, 6 tion

Aquatic Organisms Testing

850.1010 Acute fresh- CR R NR NR R --- TEP 2, 7 water inverte- brates toxicity

850.1075 Acute fresh- CR R NR NR R --- TEP 7 water fish tox- icity

850.1025 Acute estuarine CR CR R CR CR TGAI TGAI 8, 9 850.1035 and marine 850.1045 organisms 850.1055 toxicity 850.1075

Acute estuarine CR CR NR NR CR --- TEP 7, 8 and marine organisms toxicity

850.1400 Fish early-life CR R R CR R TGAI TGAI 10 stage

850.1300 Aquatic inverte- CR R R CR R TGAI TGAI 10 850.1350 brate life- cycle

850.1500 Fish life-cycle CR CR CR CR CR TGAI TGAI 11, 12

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00056 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59437

TABLE — ANTIMICROBIAL NONTARGET ORGANISM DATA REQUIREMENTS—Continued

Use Pattern Test Substance to Support High Environmental Exposure Guideline Data Require- Low Envi- Industrial Test Note Number ment ronmental Processes and Antifoulant No. Exposure Water Sys- Coatings Wood Pre- Aquatic MP EP tems(Once- and Paints servatives Areas Through)

850.1710 Aquatic orga- CR CR CR CR CR TGAI.PAI, TGAI.PAI, 13 850.1730 nisms, bio- degradate degradate 850.1850 availability, biomagnifica- tion, toxicity tests

850.1950 Simulated or ac- CR CR CR CR CR TEP TEP 14, 15, 16 tual field test- ing for aquatic organisms

Sediment Testing

850.1735 Whole sedi- CR CR R CR CR TGAI TGAI 15, 17 ment; acute freshwater in- vertebrates

850.1740 Whole sedi- CR CR R CR CR TGAI TGAI 15, 17, 19 ment; acute marine inver- tebrates

None Whole sedi- CR CR CR CR CR TGAI TGAI 15, 18, 19 ment; chronic invertebrates fresh-water and marine

Insect Pollinator Testing

850.3020 Honeybee acute CR NR NR CR NR TGAI TGAI 20 contact

850.3030 Toxicity of resi- CR NR NR CR NR TGAI TEP or 21 dues to hon- treated eybees wood

(f) Test notes. The following test notes 4. For low environmental exposures, its transformation products, especially apply to the data requirements in the industrial processes and water systems (once- preceding or during the breeding season. table to paragraph (e) of this section: through), antifoulant paints and coatings, and ii. The pesticide or any of its major 1. For low environmental exposures, data wood preservatives, data are required for one metabolites or degradation products are are required for one avian species. For waterfowl species, if the avian acute oral stable in the environment to the extent that industrial processes and water systems (once- LD50 (TGAI testing) is less than or equal to a potentially toxic amount may persist in through), antifoulant paints and coatings, 100 mg a.i./kg and a.i. residues or its avian feed. wood preservatives, and aquatic areas, data principal transformation products are likely iii. The pesticide or any of its major are required for one waterfowl species and to occur in avian feed items. Data on one metabolites or degradation products are one upland game bird species. upland game bird species are required if the stored or accumulated in plant or animal 2. Data are required on one freshwater avian dietary LC50 in the first species tested tissues, as indicated by the octanol/water aquatic invertebrate species. is less than or equal to 500 ppm a.i. in the partition coefficient (Kow is greater than or 3. For low environmental exposures, data diet. equal to 1,000), accumulation studies, are required on one species of fish, either one 5. For aquatic areas, data are required on metabolic release and retention studies, or as cold water species or a warm water species. one waterfowl species and one upland game indicated by structural similarity to known Testing on a second species is required if the bird species. bioaccumulative chemicals. active ingredient or principal transformation 6. For low environmental exposures, iv. Any other information, such as that products are stable in the environment and industrial processes and water systems (once- derived from mammalian reproduction through), antifoulant paints and coatings, and the LC50 in the first species is greater than 1 studies that indicate that reproduction in ppm or 1mg/L. For all other use patterns, wood preservatives, data are required if one terrestrial vertebrates may be adversely data are required on two species of fish, one or more of the following criteria are met: affected by the anticipated use of the cold water species and one warm water i. Birds may be subjected to repeated or pesticide product. species. continued exposure to the pesticide or any of

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00057 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59438 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

7. TEP testing is required for any product 13. Not required when: initiation of the study. Details for developing which meets one or more of the following i. The octanol/water partition coefficients protocols are available from the Agency. conditions: of the pesticide and its major degradates are i. The estimated environmental less than 1,000; or § 158.2250 Nontarget plant protection. concentration (EEC) in the aquatic ii.There are no potential exposures to fish (a) General. Subpart B of this part and environment is equal to or greater than one- and other nontarget aquatic organisms; or § 158.2201 describe how to use the table half the LC50/EC50 of the TGAI when the end- iii. The hydrolytic half-life is less than 5 in paragraph (e) of this section to use product is used as directed. days at pH 5, 7, and 9. ii. An ingredient in the end-use product determine the nontarget plant protection 14. Environmental chemistry methods used data requirements for a particular other than the active ingredient is expected to generate data associated with this study to enhance the toxicity of the active must include results of a successful antimicrobial pesticide product. Notes ingredient or to cause toxicity to aquatic confirmatory method trial by an independent that apply to an individual test organisms. laboratory. Test standards and procedures for including specific conditions, 8. Data are required on one estuarine/ independent laboratory validation are qualifications, or exceptions are listed marine mollusk, one estuarine/marine available as addenda to the guideline for this in paragraph (f) of this section. invertebrate, and one estuarine/marine fish test requirement. (b) Low environmental exposures. For species. 15. Protocols must be approved by the the purpose of determining data 9. For low environmental exposures, Agency prior to the initiation of the study. industrial processes and water systems (once- requirements, the low environmental Details for developing protocols are available exposure grouping of use patterns through), wood preservatives, and aquatic from the Agency. areas, data are required if the pesticide includes the following use patterns or 16. Data are required if the intended use residues from the parent compound and/or pattern, and the physical/chemical properties partial use patterns: transformation products are likely to enter and environmental fate characteristics of the (1) Agricultural premises and the estuarine/marine environment. antimicrobial indicate significant potential equipment. 10. For low environmental exposures, data exposure and based on the results of the (2) Food-handling/storage are required if pesticide residues from the parent compound or transformation products acute and chronic aquatic organism testing establishments, premises, and are likely to enter freshwater or estuarine/ significant impairment of nontarget aquatic equipment. marine environments, as determined by the organisms could result. (3) Commercial, institutional and Agency. For wood preservatives, data are 17. Data are required if the half-life of the industrial premises and equipment. required if pesticide residues from the parent pesticide in the sediment is equal to or less (4) Residential and public access compound, transformation products, and/or than 10 days in either the aerobic soil or premises. leachates from preservative-treated wood are aquatic metabolism studies, and if one or more of the following conditions are met: (5) Medical premises and equipment. likely to enter freshwater or estuarine/marine (6) Human drinking water systems. environments, as determined by the Agency. i. The soil partition coefficient (Kd) is equal Testing should be conducted with the most to or greater than 50. (7) Materials preservatives. sensitive organism (either freshwater or ii. The log Kow is equal to or greater than (8) Swimming pools. estuarine/marine vertebrates, or freshwater or 3. (9) Recirculating industrial processes estuarine/marine invertebrates), as iii. The Koc is equal to or greater than and water systems in which the treated determined from the results of the acute 1,000. water is re-used repeatedly within the toxicity tests (acute EC50 freshwater 18. Data are required if the EEC in system. sediment is > 0.1 of the acute LC /EC invertebrates; acute LC50/EC50 estuarine and 50 50 (c) High environmental exposures. For values and if one or more of the following marine organisms; acute freshwater fish the purposes of determining data LC .) conditions are met: 50 requirements, the high environmental 11. Data are required on estuarine /marine i. The soil partition coefficient (Kd) is equal species if the product is intended for direct to or greater than 50 L/kg. exposure grouping of use patterns application to the estuarine or marine ii. The log Kow is equal to or greater than includes the following use patterns or environment, or the product is expected to 3. partial use patterns: enter this environment in significant iii. The Koc is equal to or greater than (1) Once-through industrial processes concentrations (as determined by the 1,000. and water systems in which the water Agency) because of its expected use or 19. Sediment testing with estuarine/marine is not re-used, and is released after a mobility patterns. test species is required if the product is single cycle through the system. 12. Data are required on freshwater species intended for direct application to the if the end-use product is intended to be estuarine or marine environment or the (2) Antifoulant paints and coatings. applied directly to water, or is expected to be product is expected to enter this environment (3) Wood preservatives. transported to water from the intended use in significant concentrations (as determined (4) Aquatic areas. site, and when one or more of the following by the Agency) either by runoff or erosion, (d) Key. MP = Manufacturing use conditions apply: because of its expected use or mobility product; EP = End use product; R = i. If the Estimated Environmental pattern. Required; CR = Conditionally required; Concentration (EEC) in water is equal to or 20. Data are required only for beehive NR = Not required; TGAI = Technical greater than 0.1 of the no-observed-effect applications when the beehive (empty or grade of the active ingredient; TEP = concentration or no-observed-effect level occupied) is treated. (NOEC/NOEL) in the fish early-life stage or 21. If beehives are constructed of treated Typical end-use product. invertebrate life-cycle tests. wood a study similar to ‘‘Honey Bee Toxicity (e) Table. The following table shows ii. If studies of other organisms indicate of Residues on Foliage’’ is required using the data requirements for nontarget that the reproductive physiology of fish may treated wood instead of the foliage. Protocols plant protection. The test notes appear be affected. must be approved by the Agency prior to the in paragraph (f) of this section.

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00058 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59439

TABLE — NONTARGET PLANT PROTECTION DATA REQUIREMENTS

Use Pattern Test Substance to Support High Environmental Exposure Guideline Data Re- Industrial Test Note Number quirement Low Environ- Processes No. mental Exposure and Water Antifoulant Wood Aquatic MP EP Sys- Coatings Preserva- Areas tems(Once- and Paints tives Through)

850.4225 Seedling CR R R R R TEP TEP 1, 2 emer- gence, Tier II - dose re- sponse

850.4250 Vegetative CR CR NR R R TEP TEP 1, 3 vigor, Tier II - dose response

850.4400 Aquatic plant CR R R R R TGAI, TEP TGAI, TEP 2, 4 growth (aquatic vascular plant) Tier II - dose response

850.5400 Aquatic plant R R R R R TGAI, TEP TGAI, TEP 4, 5, 6 growth (algal) Tier II (dose response)

850.4300 Terrestrial CR CR CR CR CR TEP TEP 7, 8, 9 field

850.4450 Aquatic field CR CR CR CR CR TEP TEP 7, 8, 9

(f) Test notes. The following test notes in the end-use product, other than the active Details for developing protocols are available apply to the data requirements in the ingredient, is expected to enhance the from the Agency. toxicity of the active ingredient. table to paragraph (e) of this section: § 158.2260 Applicator exposure. 1. Data on only one plant species (rice, 5. One Tier II (dose response) study, Oryza sativa) are required. conducted with Selenastrum capricornutum, (a) General. Subpart B of this part and 2. For low environmental exposures, data is required for the low environmental § 158.2201 describe how to use the table are required if the aquatic (algal) plant exposure category grouping. If the results of in paragraph (d) of this section to growth Tier II study demonstrates this study exhibits detrimental effects (is less determine the applicator exposure data detrimental effects at less than 1.0 ppm or than 1.0 ppm or mg/L), then additional Tier requirements for antimicrobial pesticide mg/L. II (dose response) studies are required on products. Notes that apply to an 3. For low environmental exposures, and three species (Anabaena flos-aquae, Navicula individual test including specific industrial processes and water systems (once- pelliculosa, and Skeletonema costatum. 6. For industrial processes and water conditions, qualifications, or exceptions through), data are required if one or more of are listed in paragraph (e) of this the following criteria are met: systems (once-through), antifoulant coatings i. The octanol/water partition coefficient and paints, wood preservatives, and aquatic section. (1) If EPA determines that industrial (Kow) for the active ingredient or principal areas, Tier II (dose response) studies are transformation products ≥ 1,000 for the active required on four species (Anabaena flos- standards, such as the workplace ingredient or principal transformation aquae, Navicula pelliculosa, Skeletonema standards set by the Occupational Safety products; costatum, and Selenastrum capricornutum. and Health Administration, provide ii. The hydrolysis half-life of the active 7. Environmental chemistry methods used adequate protection for a particular ingredient or principal transformation to generate data must include the results of pesticide or a particular use pattern, products in water is > 4 days. a successful confirmatory method trial by an applicator exposure data may not be iii. The results of the ready independent laboratory. required for that pesticide or the use biodegradability study [§ 158.2280] indicate 8. Tests are required on a case-by-case pattern. Applicants should consult with that the active ingredient or principal basis based on the results of lower tier plant degradation products are not biodegradable protection studies, adverse incident reports, the Agency on appropriate testing before in 28 days, i.e. the biodegradation curve has intended use pattern(s), and environmental the initiation of studies. not reached a plateau for at least three fate characteristics that indicate potential (2) The Agency may accept surrogate determinations within the 28 days. exposure. exposure data estimations from other 4. For TEP testing, data are required for the 9. Protocols must be approved by the sources to satisfy applicator exposure applicant’s end-use product if an ingredient Agency prior to the initiation of the study. data requirements if the data meet the

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00059 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59440 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

basic quality assurance, quality control, applications to residential sites. have been observed in any applicable good laboratory practice, and other Residential uses are limited to non- toxicity studies. scientific requirements set by EPA. In occupational, i.e., non-professional, ii. Scientifically sound order to be acceptable, the Agency must antimicrobial applications. Both epidemiological or poisoning incident find that the surrogate exposure data occupational and residential applicator data indicate that adverse health effects estimations have adequate information data may be required for the same may have resulted from handling of the to address applicator exposure data product. pesticide. requirements and contain enough (b) Criteria for testing. Applicator adequate replicates of acceptable quality (2) Exposure criteria. i. Dermal exposure data described in paragraph to reflect the specific use prescribed on exposure may occur during use. (d) of this section are required based on the label and the applicator activity of toxicity and exposure criteria. Data are ii. Respiratory exposure may occur concern, including formulation type, required if a product meets, as during use. application methods and rates, type of (c) Key. R = Required; CR = activity, and other pertinent determined by the Agency, at least one Conditionally required; TEP = Typical information. The Agency will consider of the toxicity criteria in paragraph using such surrogate data for evaluating (b)(1) of this section, and at least one of end-use product. human exposure on a case-by-case basis. the exposure criteria in paragraph (b)(2) (d) Table. The following table shows (3) Occupational uses include not of this section. the data requirements for applicator only handlers, mixers, loaders, and (1) Toxicity criteria. i. Evidence of exposure. The test notes appear in applicators, but also commercial potentially significant adverse effects paragraph (e) of this section.

TABLE — ANTIMICROBIAL APPLICATOR EXPOSURE DATA REQUIREMENTS

Guideline Number Data Requirements Occupational Residential Test Substance Test Note No

875.1100 Dermal outdoor exposure R R TEP 1, 2, 3

875.1200 Dermal indoor exposure R R TEP 1, 2, 3, 4

875.1300 Inhalation outdoor exposure R R TEP 1, 2, 3

875.1400 Inhalation indoor exposure R R TEP 1, 2, 3, 4

875.1500 Biological monitoring CR CR TEP 1, 2, 3

875.1600 Data reporting and calculations R R TEP 5

875.1700 Product use information R R TEP —

(e) Test notes. The following test concerning exposure, toxicity, and other data and Health Administration, provide notes apply to the data requirements in requirements for ‘‘open’’ and ‘‘closed’’ MWF adequate protection for a particular the table to paragraph (d) of this section: systems. pesticide or a particular use pattern, 1. Protocols must be approved by the 5. Data reporting and calculations are required when handler exposure data are post-application exposure data may not Agency prior to the initiation of the study. be required for that pesticide or the use Details for developing protocols are available required. from the Agency. pattern. Applicants should consult with § 158.2270 Post-application exposure. 2. Biological monitoring data may be the Agency on appropriate testing before submitted in addition to, or in lieu of, dermal (a) General. Subpart B of this part and the initiation of studies. and inhalation passive dosimetry exposure § 158.2201 describe how to use the table (3) The Agency may accept surrogate data, provided the human pharmacokinetics in paragraph (d) of this section to exposure data estimations from other of the pesticide or metabolite/analog determine the post-application exposure sources to satisfy applicator exposure compounds (i.e., whichever method is data requirements for antimicrobial selected as an indicator of body burden or data requirements if the data meet the pesticide products. The data generated internal dose) allow for the back calculation basic quality assurance, quality control, during these studies are used to to the total internal dose. good laboratory practice, and other 3. For products with both indoor and determine the quantity of pesticide to outdoor uses, and similar conditions of use, which people may be exposed after scientific requirements set by EPA. In data are generally required for the indoor application. Notes that apply to an order to be acceptable, the Agency must applications only. However, data for outdoor individual test, including specific find that the surrogate exposure data uses are required if the Agency expects conditions, qualifications, or exceptions estimations have adequate information outdoor uses to result in greater exposure to the designated test, are listed in to address applicator exposure data than indoor uses (e.g., higher use rates and requirements and contain enough application frequency, or longer exposure paragraph (e) of this section. duration, or application methods/equipment (1) For all end-use products, post- adequate replicates of acceptable quality create potential for increased dermal or application exposure data are required to reflect the specific use prescribed on inhalation exposure in outdoor versus indoor when certain toxicity criteria are met the label and the applicator activity of use sites). In certain cases, when a pesticide and the human activities associated concern, including formulation type, is used both indoors and outdoors under with the pesticide’s use pattern can lead application methods and rates, type of dissimilar conditions of use, the Agency may activity, and other pertinent require submission of applicator exposure to potential adverse exposures. data for both use patterns. (2) If EPA determines that industrial information. The Agency will consider 4. For metal working fluids (MWFs), the standards, such as the workplace using such surrogate data for evaluating Agency can provide written guidance standards set by the Occupational Safety human exposure on a case-by-case basis.

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00060 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59441

(b) Criteria for Testing. Post- application exposure to residues of the application of the antimicrobial application exposure data described in antimicrobial pesticides could occur as pesticide to indoor spaces or surfaces. paragraph (d) of this section are the result of, but is not limited to, (B) Residential human post- required based on toxicity and exposure worker re-entry into treatment sites, application exposure to pesticide criteria. Data are required if a product clean-up and equipment maintenance residues could occur following the meets, as determined by the Agency, at tasks, handling wood preservative- application of the antimicrobial least one of the toxicity criteria in treated wood, or other work-related pesticide to indoor spaces or surfaces at paragraph (b)(1) of this section, and at activity. least one of the exposure criteria in residential sites, such as, but not limited (B) Residential human post- to homes, daycare centers, hospitals, paragraph (b)(2) of this section. application exposure to residues of (1) Toxicity criteria. (i) Evidence of schools, and other public buildings. antimicrobial pesticides could occur potentially significant adverse effects following the application of (c) Key. R = Required; CR = have been observed in any applicable antimicrobials pesticides to outdoor Conditionally required; NR = Not toxicity studies. areas and spaces at residential sites, required; TEP = Typical end-use (ii) Scientifically sound product. epidemiological or poisoning incident such as, but not limited to homes, data indicate that adverse health effects daycare centers, and other public (d) Table. The following table shows may have resulted from handling of the buildings. the data requirements for post- pesticide. (ii) Indoor uses. (A) Occupational application exposure. The test notes (2) Exposure criteria. (i) Outdoor uses. human post-application exposure to appear in paragraph (e) of this section. (A) Occupational human post- pesticide residues could occur following

TABLE — ANTIMICROBIAL POST-APPLICATION EXPOSURE DATA REQUIREMENTS

Use Sites Guideline Number Data Requirement Test Substance Test Note Occupational Residential No.

875.2200 Soil residue dissipation CR CR TEP 1, 2, 3

875.2300 Indoor surface residue dissipation R R TEP 1, 3, 4, 5, 6

875.2400 Dermal exposure R R TEP 1, 3, 7, 8

875.2500 Inhalation exposure R R TEP 1, 8, 9

875.2600 Biological monitoring CR CR TEP 1, 8, 10

875.2700 Product use information R R TEP ---

875.2800 Description of human activity R R TEP ---

875.2900 Data reporting and calculations R R TEP 11

875.3000 Non-dietary ingestion exposure NR R TEP 1, 12

(e) Test notes. The following test indoor surfaces while participating in typical 9. Data are required for occupational sites notes apply to the data requirements in activities. if the vapor pressure is greater than 1E–3 the table to paragraph (d) of this section: 6. Data are required for residential sites. mmHg at 25° C and there is the potential for 1. Protocols must be approved by the This includes but is not limited to the bystander exposure. Data are also required if Agency prior to the initiation of the study. following use patterns: commercial, aerosols are generated where bystanders may Details for developing protocols are available institutional, and industrial premises and be exposed. from the Agency. equipment (including residential school and 10. Biological monitoring data are required daycare institutions); residential and public 2. For residential wood preservative uses, when passive dosimetry techniques are not access premises; material preservatives data are required if there is likely to be soil applicable for a particular exposure scenario (including those used in residential products in contact with or adjacent to treated wood, (such as a swimmer/spa exposure) and including but not limited to paints and exposure estimates from modeling including but not limited to decks, play sets, plastic toys) and wood preservatives (when techniques used in conjunction with the and gazebos. contact with treated wood is likely to occur). toxicity data indicate a risk of concern. 3. The applicant must submit residue 7. Data are required for occupational and 11. Data reporting and calculations are dissipation data in conjunction with dermal residential use sites if the human activity exposure data, to establish chemical transfer data indicate the potential for post- required when any post-application exposure coefficients used to estimate transfer of application dermal exposures while monitoring data are required. residues to human skin. participating in typical activities. 12. Data are required for residential sites if 4. For wood preservatives, data are 8. Biological monitoring data may be post-application exposures, particularly required for treated wood surfaces where submitted in addition to, or in lieu of, dermal those of children, are likely. The selection of post-application contact with treated wood is and inhalation passive dosimetry exposure a sampling method will depend on the non- anticipated. data provided the human pharmacokinetics dietary pathway(s) of interest. Data must be 5. For occupational uses, data are required of the pesticide or metabolite/analog generated to consider all potential pathways if the pesticide is applied to or around compounds (i.e., whichever method is of non-dietary ingestion exposure that are surfaces, and if the human activity data selected as an indicator of body burden or applicable (e.g., soil ingestion, hand-to- indicate that workers are likely to have post- internal dose) allow for a back-calculation to mouth transfer, and object-to-mouth transfer application dermal contact with treated the total internal dose. of surface residues).

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00061 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59442 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

§ 158.2280 Environmental fate. degradation products that occur in water is re-used repeatedly within the (a) General. Subpart B of this part and wood post-treatment or occur as system. § 158.2201 describe how to use the table dislodgeable residues (such as hand (c) High environmental exposures. For in paragraph (e) of this section to contact with treated wood) or leachate the purposes of determining data determine the environmental fate data residues (such as from soil or water requirements, the high environmental requirements for antimicrobial pesticide contact with treated wood). exposure grouping of use patterns products. Notes that apply to an (b) Low environmental exposures. For includes the following use patterns or individual test including specific the purpose of determining data partial use patterns: conditions, qualifications, or exceptions requirements, the low environmental (1) Once-through industrial processes are listed in paragraph (f) of this section. exposure grouping of use patterns and water systems in which the water (1) Environmental fate data are includes the following use patterns or is not re-used, and is released after a required to support the registrations of partial use patterns: single cycle through the system. all end-use and manufacturing-use (1) Agricultural premises and (2) Antifoulant paints and coatings. antimicrobial products. equipment. (3) Wood preservatives. (2) If the Agency believes that the (2) Food-handling/storage transformation products of the parent establishments, premises, and (4) Aquatic areas. compound are more toxic, persistent, or equipment. (d) Key. MP = Manufacturing use bioaccumulative than the parent (3) Commercial, institutional and product; EP = End use product; R = compound, or have been shown to cause industrial premises and equipment. Required; CR = Conditionally required; adverse effects in mammalian or aquatic (4) Residential and public access NR = Not required; TGAI = Technical reproductive studies, then data on those premises. grade of the active ingredient; TEP = transformation products are also (5) Medical premises and equipment. Typical end-use product; PAIRA = Pure required to support registration. (6) Human drinking water systems. active ingredient radiolabeled. (3) For wood preservatives, the (7) Materials preservatives. (e) Table. The following table shows Agency may require data on both the (8) Swimming pools. the data requirements for environmental parent compound that is incorporated (9) Recirculating industrial processes fate. The test notes appear in paragraph into the wood, and on transformation/ and water systems in which the treated (f) of this section.

TABLE—ANTIMICROBIAL ENVIRONMENTAL FATE DATA REQUIREMENTS

Use Pattern Test Substance to Support High Environmental Exposure Guideline Industrial Test Note Number Data Requirement Low Envi- Pro-cesses No. ronmental and Water Antifoulant Wood Aquatic MP EP Exposure Sys- Coatings Preserva- Areas tems(Once- and Paints tives Through)

Degradation Studies - Laboratory

835.2120 Hydrolysis R R R R R TGAI or TGAI or 1 PAIRA PAIRA

835.2240 Photodegradation in R R R R R TGAI or TGAI or 2 water PAIRA PAIRA

835.2410 Photodegradation in NR NR NR R NR TGAI or TGAI or -- soil PAIRA PAIRA

Biodegradation Studies - Laboratory

835.1110 Activated Sludge R R NR NR NR TGAI TGAI -- Sorption Isotherm

835.3110 Ready R R NR NR NR TGAI TGAI 3 Biodegradability

850.6800 Modified Activated R R NR NR NR TGAI TGAI -- Sludge, Respiration Inhibition Test

835.3220 Porous Pot Study CR CR NR NR NR TGAI TGAI 4

Mobility Studies

835.1230 Leaching and adsorp- CR R R R R TGAI or TGAI or 5, 7 835.1240 tion/desorption PAIRA PAIRA

Metabolism Studies - Laboratory

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00062 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59443

TABLE—ANTIMICROBIAL ENVIRONMENTAL FATE DATA REQUIREMENTS—Continued

Use Pattern Test Substance to Support High Environmental Exposure Guideline Industrial Test Note Number Data Requirement Low Envi- Pro-cesses No. ronmental and Water Antifoulant Wood Aquatic MP EP Exposure Sys- Coatings Preserva- Areas tems(Once- and Paints tives Through)

835.4100 Aerobic soil metabo- CR CR NR R CR TGAI or TGAI or 5, 6, 8, 9 lism PAIRA PAIRA

835.4200 Anaerobic soil metab- CR NR NR CR NR TGAI or TGAI or 5, 8, 10 olism PAIRA PAIRA

835.4300 Aerobic aquatic me- CR R R CR R TGAI or TGAI or 5, 8, 10 tabolism PAIRA PAIRA

835.4400 Anaerobic aquatic me- CR R R CR R TGAI or TGAI or 5, 8, 10 tabolism PAIRA PAIRA

Dissipation Studies -- Field

835.6200 Aquatic (sediment) CR CR CR CR R TEP TEP 5, 11, 12, 13

Ground and Surface Water Monitoring

None Monitoring of rep- CR CR CR CR CR residue of residue of 11, 12, resentative U.S. wa- concern concern 14 ters

Special Studies

None Special leaching NR NR R R NR TGAI TEP 15, 16

(f) Test notes. The following test notes based on a weight-of-evidence evaluation of 13. For industrial processes and water apply to the data requirements in the the results of the hydrolysis, systems (once-through), antifoulant paints table in paragraph (e) of this section: photodegradation in water, activated sludge and coatings, and wood preservatives, data 1. For testing antifoulant paints and sorption isotherm, ready biodegradability, are required based on the potential for coatings, testing is to be performed with both and modified activated sludge, respiration aquatic exposure and if the weight-of- evidence indicates that the active ingredient sterile buffered distilled water and sterile inhibition tests. or principal transformation products are synthetic seawater at pH 5, 7, and 9. 7. Adsorption and desorption using a batch likely to have the potential for persistence, 2. Not required when the electronic equilibrium method is preferred. In some mobility, nontarget aquatic toxicity, or absorption spectra, measured at pHs 5, 7 and cases, as when the antimicrobial pesticide degrades rapidly, soil column leaching with bioaccumulation. 9, of the chemical and its hydrolytic 14. Data are required if the weight-of- products, if any, show no absorption or unaged or aged columns may be more appropriate to fully characterize the potential evidence indicates that the active ingredient tailing between 290 and 800 nm. or principal transformation products are mobility of the parent compound and major 3. The selection of the particular likely to occur in nontarget freshwater, transformation products. biodegradation study depends on the estuarine, or marine waters such that human 8. The environmental media (soil, water, physical and chemical properties of the test or environmental exposures are likely to substance, and the results of the activated hydrosoil, and biota) to be utilized in these occur. The Agency takes into account other sludge sorption isotherm and the modified studies must be collected from areas factors such as the toxicity of the chemical(s), activated sludge studies. representative of potential use sites. available monitoring data and the 4. Required if the pass criteria for the ready 9. For industrial processes and water vulnerability of the freshwater, estuarine, or biodegradation study are not met. This means systems (once-through), and aquatic areas, marine water resources in the antimicrobial 70% or greater removal of dissolved organic data are required for use sites that are use area. carbon and 60% or greater of theoretical intermittently dry. 15. For wood preservatives, an aquatic oxygen demand or theoretical carbon 10. For wood preservatives, data are leaching study is required. A soil leaching dioxide. These pass values must be reached required if treated wood is used in aquatic study is required if human or environmental in a 10–day window within the 28–day environments or in soils which may become exposures are likely to occur from leachates period of the test. flooded or waterlogged. that contain the active ingredient or principal 5. For low environmental exposure uses, 11. Environmental chemistry methods used transformation products from wood treated data are required based on a weight-of- to generate data associated with this study with a preservative product. For these evidence evaluation of the results of the must include results of a successful studies, the Agency accepts the following hydrolysis, photodegradation in water, confirmatory method trial by an independent methods or their equivalents: American activated sludge sorption isotherm, ready laboratory. Wood Preservers’ Association (AWPA) biodegradability, and modified activated 12. Protocols must be approved by the Method E11–97 (aquatic leaching), and sludge, respiration inhibition tests. Agency prior to the initiation of the study. AWPA Method E20–04 (soil leaching). Prior 6. For industrial processes and water Details for developing protocols are available approval of studies conducted according to systems (once-through), data are required from the Agency. E11–97 is not required. All other protocols

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00063 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59444 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

must be approved by the Agency prior to the (i) Direct food uses such as (2) Each manufacturing-use product initiation of the study. Details for developing antimicrobial products used to treat bearing directions for formulation into protocols are available from the Agency. animal or poultry drinking water, for an end-use product bearing food-uses 16. For antifoulant paints and coatings, a leaching study is required. The Agency egg washing, or fruit and vegetable described in paragraph (b)(1) of this accepts the following method or its rinses. section. equivalent: American Society for Testing and (ii) Indirect food uses such as (c) Except as described in paragraph Materials (ASTM) Method D5108–90. Prior antimicrobial products applied to a (b) of this section, residue chemistry approval of studies conducted according to surface or incorporated into a material data are not required to support a D5108–90 is not required. All other protocols that may contact food or feed. Residues must be approved by the Agency prior to the tolerance exemption if dietary exposure may be expected to transfer to such food estimates are not needed due to low initiation of the study. Details for developing or feed. Data are required regardless of protocols are available from the Agency. toxicity of the active ingredient or whether the antimicrobial is applied or theoretical (modeled) estimates of § 158.2290 Residue chemistry. impregnated for the purpose of exposure are adequate to assess dietary (a) General. Subpart B of this part and imparting antimicrobial protection to risk. § 158.2201 describe how to use the table external surfaces of the substance or (d) Key. R = Required; CR = in paragraph (f) of this section to article, or for the purpose of protecting Conditionally required; NR = Not determine the residue chemistry data the substance or article itself. required; TGAI = Technical grade of the requirements for antimicrobial pesticide (iii) Aquatic uses that have the active ingredient; TEP = Typical end- products. potential to result in residues in potable (b) Residue chemistry data are water, or in water used for livestock and use product; PAI = Pure active required for products described in this poultry drinking water, irrigation of ingredient; PAIRA = Pure active paragraph. crops, or water containing fish that may ingredient radiolabeled; the residue of (1) Each end-use product bearing label be used for human food. concern is determined by the Agency. directions for food-uses that require a (iv) Wood preservative or antifoulant (e) Table. The following table shows tolerance or tolerance exemption, products intended for treating wood that the data requirements for residue including, but not limited to the may be used for food purposes (e.g., chemistry. The test notes appear in following: lobster pots, fish cages, or fish farms). paragraph (f) of this section.

TABLE — ANTIMICROBIAL RESIDUE CHEMISTRY DATA REQUIREMENTS

Use Pattern Direct Test Note Guideline Number Data Requirement Agricul- Indirect Food Aquatic Test substance No. tural Food Contact Uses Premises Uses Uses

Supporting Information

860.1100 Chemical identity R R R R TGAI --

860.1200 Directions for use R R R R -- --

860.1550 Proposed tolerance R R R R -- 1

860.1560 Reasonable grounds in support of R R R R -- 1 petition

860.1650 Submittal of analytical reference R R R R PAI and residue of 2 standards concern

Nature of the residue

860.1300 Nature of the residue in plants CR NR R R PAIRA 3, 4, 5

860.1300 Nature of the residue in livestock R NR CR CR PAIRA or radiolabeled 6, 7, 8 plant metabolite

Analytical methods

860.1340 Residue analytical methods for en- CR CR R CR Residue of concern 9 forcement of tolerances

860.1340 Residue analytical methods for data CR CR R CR Residue of concern 10 collection

860.1360 Multiresidue method testing CR CR R CR Residue of concern 11

Magnitude of the residue

860.1380 Storage stability R R R R TEP or residue of 12 concern

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00064 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 59445

TABLE — ANTIMICROBIAL RESIDUE CHEMISTRY DATA REQUIREMENTS—Continued

Use Pattern Direct Test Note Guideline Number Data Requirement Agricul- Indirect Food Aquatic Test substance No. tural Food Contact Uses Premises Uses Uses

860.1500 Crop field trials CR CR R R TEP 13, 14

860.1520 Processed food or feed NR CR CR CR TEP 15

860.1480 Meat/milk/poultry/eggs CR CR CR CR TGAI or plant metabo- 16, 17 lite

860.1400 Potable water R NR NR R TEP 18

860.1400 Fish NR NR NR R TEP 19

860.1400 Irrigated crops NR NR NR CR TEP 20

860.1460 Food-handling NR CR R NR TEP 21

860.1540 Anticipated residues CR CR CR CR Residue of concern 22

None Migration studies NR CR NR NR TGAI 23

(f) Test notes. The following test notes 9. A residue analytical method suitable for in or on livestock feed items or intentionally apply to the data requirements in the enforcement purposes is required whenever added to drinking water. These studies, table to paragraph (e) of this section: a numeric tolerance is proposed. however, may not be required in cases where 1. A petition proposing a numerical Enforcement methods must be supported by the livestock metabolism studies indicate tolerance or a tolerance exemption is results of an independent laboratory negligible transfer of pesticide residues of required for any food or feed use subject to validation. concern to tissues, milk, and eggs at the section 408 of the FFDCA if the use is not 10. A residue analytical method suitable maximum expected exposure level for the covered by an existing tolerance or tolerance for collecting data to establish tolerances animals. exemption. must quantitate all residues of concern, as 18. Data are required for antimicrobial 2. An analytical reference standard is determined by the Agency. pesticides applied directly to water, if there required for any food or feed use requiring 11. Data are required to determine whether is the potential that the treated water could a tolerance. Material safety data sheets must the FDA/USDA multiresidue methodology be used for drinking purposes by man or accompany analytical standards as specified would detect and identify the antimicrobial animals. by OSHA in 29 CFR 1910.1200. active ingredient and its metabolites. 19. For aquatic uses, data for fish are 3. For agricultural premises, data are 12. Data are required for any food or feed required for antimicrobial pesticides applied required for postharvest storage of plant use requiring magnitude of the residue directly to water inhabited, or which will be commodities. studies unless analytical samples are stored inhabited, by fish that may be caught or 4. Data are required for direct food contact frozen for 30 days or less, and the active harvested for human consumption. uses, excluding egg washes, to determine the ingredient is not known to be volatile or 20. Data are required for antimicrobial transformation products in representative labile. pesticides applied directly to water that foods. 13. Residue data are required if could be used for irrigation or to irrigation 5. Data are required to support applications antimicrobial chemicals are to be applied to facilities such as ditches. to water if any residues could occur in mushroom houses, empty or occupied 21. Data are required whenever a pesticide irrigated crops, or to crops treated directly in beehives, wood used to construct beehives, is to be used in a food-handling or feed the field. or any use which could result in residues in handling establishment unless theoretical 6. Data are required when an antimicrobial food or feed. calculations, radiolabeled laboratory data, the pesticide is applied directly to livestock, to 14. If the antimicrobial chemical is applied nature of the residue study, or other data livestock premises, to livestock drinking to growing crops in the field, then the show that residues will not occur in food or water, to livestock feed, or to crops used for requirements of 40 CFR part 158, subpart O feed. Use in a food-handling establishment livestock feed. (terrestrial food or feed use pattern) apply. also includes fresh fruits and vegetables that 7. Data are required for aquatic uses if there 15. Data on the nature and level of residues undergo a rinse with either a sanitizing is the potential that the treated water could in processed food or feed are required if solution, or with a disinfectant followed by be used eventually for drinking purposes by residues could potentially concentrate on a potable water rinse. livestock. processing, thus requiring the establishment 22. Data are required when estimates of 8. If results from the plant metabolism of a separate tolerance higher than that of the risk using residues at the tolerance level may study show differing metabolites in plants raw agricultural commodity. result in a risk of concern. These data may from those found in animals, then additional 16. Data are required when the pesticide include washing, cooking, processing or livestock metabolism study(ies) involving use is a direct application to livestock. degradation studies as well as market basket dosing with the plant metabolite(s) may be 17. Data are required if livestock premises surveys for a more precise residue required. are treated or if pesticide residues are present determination.

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00065 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS 59446 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules

23. Migration of residue data are required a risk of concern. Protocols must be approved Authority: 7 U.S.C. 136 – 136y. for antimicrobial pesticides applied to hard by the Agency prior to the initiation of the food surfaces or incorporated into substrates study. Details for developing protocols are Part 161 [Removed] available from the Agency. (wood, plastic, paper, cloth, rubber or similar 7. Part 161 is removed: products) intended for contact with food or PART 161—[AMENDED] [FR Doc. E8–23127 Filed 10–7–08; 8:45 am] feed when theoretical (modeled) estimates of the amount of antimicrobial residue 6. The authority citation for part 161 BILLING CODE 6560–50–S transferred to the food or feed may result in continues to read as follows:

VerDate Aug<31>2005 21:23 Oct 07, 2008 Jkt 214001 PO 00000 Frm 00066 Fmt 4701 Sfmt 4702 E:\FR\FM\08OCP2.SGM 08OCP2 sroberts on PROD1PC70 with PROPOSALS