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Page 1 of 234 EO 12866_Antimicrobial Data Requireme nts_RIN 2070-AD30_FRM_2011-09-19.docx 1 Draft document submitted Interagency review. 2 BILLING CODE 6560–50–P 3 ENVIRONMENTAL PROTECTION AGENCY 4 40 CFR Part 158 and 161 5 EPA–HQ–OPP–2008–0110; FRL– XXXX–X 6 RIN 2070–AD30 7 Data Requirements for Antimicrobial Pesticides 8 AGENCY: Environmental Protection Agency (EPA). 9 ACTION: Final rule. 10 SUMMARY: EPA is revising and updating the dat a requirements for antimicrobial 11 pesticide products, which reflect current scientific and regulatory practices. 12 Besides providing the regulated community with clearer and more transparent 13 information, the updated data requirements further enhance EPA’s ability to make 14 regulatory decisions about the human health, and environm ental fate and effects 15 of antimicrobial pesticide products. 16 DATES: This final rule is effective [ insert date 60 days after date of publication in 17 the Federal Register ]. 18 ADDRESSES: EPA has established a docket for this action under docket 19 identification (ID) number EPA–HQ–O PP–2008–0110. All documents in the 20 docket are listed in the do cket index available at http://www.regulations.gov

. 21 Although listed in t he index, some information is not publicly available, e.g., 22 Confidential Business Info rmation (CBI) or other info rmation whose disclosure is 23 restricted by statute. Certain other materi al, such as copyrighted material, is not 24*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 2 of 234 placed on the Internet and wi ll be publicly available on ly in hard copy form. 25 Publicly available docket materials are available in the electronic docket at 26 http://www.regulations.gov , or, if only available in hard copy, at the OPP 27 Regulatory Public Docket in Rm. S–440 0, One Potomac Yard (South Bldg.), 2777 28 S. Crystal Dr., Arlingt on, VA. The Docket Facility is open from 8:30 a.m. to 4 p.m., 29 Monday through Friday, excluding legal ho lidays. The Docket Facility telephone 30 number is (703) 305–5805. 31 FOR FURTHER INFORMATION CONTACT: Kathryn Boyle, Field and External 32 Affairs Division (7506P), Office of Pestic ide Programs, Environm ental Protection 33 Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460–0001; telephone 34 number: (703) 305-6304; e-mail address: boyle.kathryn@epa.gov , or contact 35 Scott Drewes, same address; telephone number (703) 347-0107; email address: 36 drewes.scott@epa.gov

. 37 SUPPLEMENTARY INFORMATION: 38 I. General Information 39 A. Does this Action Apply to Me? 40 You may be affected by this action if you are a producer of pesticide 41 products (NAICS 32532), antifoulants (N AICS 32551), antimicrobial pesticides 42 (NAICS 32561) or wood preservatives (NAICS 32519), importers of such 43 products, or any person or company who seeks to register an antimicrobial, 44 antifoulant coating, ballast water treatment, or wood preservative pesticide or to 45 obtain a tolerance for such a pesticide. This listing is not intended to be 46 exhaustive, but rather provides a guide for readers regarding entities likely to be 47*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 3 of 234 affected by this action. Other types of entities not listed above could also be 48 affected. The North Amer ican Industrial Classification System (NAICS) codes 49 have been provided to assist you and other s in determining whether this action 50 might apply to certain entities. If you have any questi ons regarding the 51 applicability of this action to a particular entity, please contact Nader Elkassabany, 52 Chief of the Risk Assessment and Science Support Branch in the Antimicrobials 53 Division of the Office of Pesticide Pr ograms at (703) 308- 8783 or via email, 54 elkassabany.nader@epa.gov

. 55 B. How Can I Access Electronic Copies of this Document? 56 57 In addition to accessing an electronic copy of this Federal Register document through 58
the electronic docket at http:// www.regulations.gov , you may access this Federal Register 59 document electronically through the EPA Internet under the ‘‘ Federal Register ’’ listings at 60 http://www.epa.gov/fedrgstr . You may also access a frequently updated electronic version of 40 61 CFR parts 158 and 161 through the Government Printing Office’s pilot e-CFR site at http:// 62 www.gpoaccess.gov/ecfr

. To access the harmonized test guidelines referenced in this document 63 electronically, please go to http://www.epa.gov/ocspp and select “Test Methods and Guidelines.” 64 II. Background 65 A. What Action is the Agency Taking? 66 The Environmental Protection Agency (EPA or the Agency) is revising and 67 updating the data requirements fo r antimicrobial pesticides in Title 40 of the Code 68 of Federal Regulations (CFR) in subpart W of part 158. Subpart W sets out data 69 requirements specific to antimicrobial products that are described by the 70 antimicrobial use patterns and use expos ure considerations particular to 71 antimicrobials. With the promulgati on of part 158, subpart W, EPA is removing 72*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 4 of 234 part 161, entitled “Data Require ments for Registration of Antimicrobial Pesticides” 73 as it is no longer needed. 74 Antimicrobial pesticides are used to c ontrol microbiological contamination 75 in healthcare applications, and deteriora tion in industrial, commercial, and 76 consumer products. Nearly 60 percent of antimicrobial products are registered as 77 public health products (as defined at FIFRA 2(gg)) to control infectious 78 microorganisms in hospitals and other health care environments. Public health 79 products are intended to control microorganism s infectious to humans in any 80 inanimate environment. The common public health antimicrobial products include 81 sterilants, disinfectants, and sanitizers. Nonpublic health pr oducts are sold and 82 distributed for use to control growth of algae, odor-causing bacteria, bacteria 83 which cause spoilage, deterioration or fouling of materials and microorganisms 84 infectious only to animals. Other exam ples of nonpublic health products include 85 products used in cooling towers, jet fuel , paints, and treatments for textile and 86 paper products 87 Within this final rule EPA is using the term antimicrobials to collectively 88 refer to antimicrobial pesticides, ant ifoulant coatings and paints, and wood 89 preservatives. 90 B. What is the Agency's Aut hority for Taking this Action? 91 This action is issued under the authority of sections 2, 3, 4, 5, 10, 12, and 92 25 of the Federal Insecticide and Rodenticide Act (FIFRA) as amended and 93 section 408 of the Federal Food, Drug, and Cosmetic Act (FFDCA). The data 94 required for a registration, reregistrati on, experimental use permit (EUP), or 95 tolerance/tolerance exemption for antim icrobials are listed in 40 CFR part 158. 96*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 5 of 234 C. Next Steps after this Rulemaking 97 Over the next several years, EPA’s Offi ce of Pesticide Programs (OPP) is 98 committed to improving and transfo rming our approach to pesticide risk 99 management by enhancing our ability to us e integrated approache s to testing and 100 assessment. Over the next 5 years, the Pe sticide Program plans to maximize use 101 of existing data from similar com pounds, including information from new in silico 102 and in vitro predictive models and expos ure modeling to target in vivo toxicity 103 testing that is needed to assess and m anage chemical risks appropriately. 104 Over the next decade, as experienc e is gained and as our understanding of 105 toxicity pathways increases, an enhanced integrated testing and assessment 106 approach will be implem ented for all pesticides. The approach will fully integrate 107 hazard and exposure information using advanced computer modeling of new in 108 vitro data and an understanding of toxicity pathways to better predict risks and to 109 determine what additional data are necessary to provide a sound basis to manage 110 risks of concern. Data from improved biomarkers of exposure and biological 111 outcomes from population-based studi es will be used to evaluate the 112 effectiveness of this new risk assessment paradigm, to readily identify early 113 effects in exposed populations , and to improve the approach. 114 Current Agency scientific and regulator y practice provides the foundation 115 for this final rule. While current prac tice is still largely dependent on animal ( in 116 vivo ) testing, this rule is one milestone towa rds the Agency’s longer term vision for 117 21st Century Toxicology and new integrated testing strategies. OPP believes that 118 certain classes of chemicals, such as antimicrobial pesticides, provide an 119*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 6 of 234 appropriate starting point fo r OPP’s planned transformation. Many antimicrobials 120 have both pesticidal and non-pesticidal uses . In addition, m any antimicrobial 121 products are regulated under multiple juri sdictions. Thus, many antimicrobial 122 chemicals have been assessed by other regulatory programs and agencies. The 123 ready availability of published literatur e and publicly-available assessments offer a 124 unique opportunity for the applicant to us e the available information as a starting 125 point for fulfilling data requirements, and, when appropriate, to use computer 126 modeling and/or in-vitro data to supplement or fulf ill data requirements. For 127 example, OPP established a vo luntary pilot program for eye irritation testing of 128 certain antimicrobial pesticides usi ng non–animal test methods. OPP will 129 continue to evaluate use of new in vitro and computer-based approaches in our 130 hazard and risk assessment processes as the technologies are sufficiently 131 developed and peer-reviewed. Certain tools are already available or anticipated 132 to become available in the near term incl uding, (Quantitative) Structure-Activity133 Relationship (Q)SAR/expert systems and in vitro high through put screening 134 technologies. Furthermore, in conjunction with the International Life Sciences 135 Institute (ILSI), OPP is curr ently pursuing the development of an application of the 136 thresholds of toxicological concern ( TTC) concept to evaluate antimicrobial 137 pesticides. In collaboration with O PP, EPA’s Office of Research and 138 Development is providing momentum for achieving the vision of 21 st Century 139 Toxicology by developing and evaluating ne w technologies in molecular, cellular, 140 and computational sciences to supplement or replace more traditional methods of 141 data development. OPP believes that its goal of using 21 st Century science in 142*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 7 of 234 integrated approaches to te sting and assessment is achievable with strong 143 scientific and stakeholder support thr ough a transparent process. As the 144 enhanced integrated testing and assessment approach matures, based on these 145 scientific advances, EPA may determine to update its data requirements to reflect 146 evolving program needs as s pecified in § 158.30(c). 147 D. Acronyms Used in this Document 148 The acronyms used throughout this document have the following meaning: 149 ACGIH means the American Conferenc e of Governmental and Industrial 150 Hygenists 151 AD means EPA’s Antimicrobial Division in OPP 152 ARTCA means the Antimicrobial R egulation Technical Correction Act 153 ASRI means Activated Sludge, Re spiration Inhibition Test 154 ASSI means Activated Sludge Sorption Isotherm 155 ASTM means the American Society for Testing and Materials 156 AWPA means the American Wood Protecti on Association, formerly American 157 Wood Preservatives Association 158 “CR” means conditionally required 159 CFR means the Code of Federal Regulations 160 CDC means the Centers for Disease Control and Prevention 161 COC means concentration of concern 162 CWA means the Clean Water Act 163 DCI means Data Call-in 164 D-t-D means down the drain 165*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 8 of 234 EA means economic analysis 166 EDSP means Endocrine Disr upter Screening Program 167 E-FAST means Exposure and Fate Assessment Screening Tool 168 EP means end-use product 169 EPA or the Agency means the United States Environmental Protection Agency 170 ESA means the Endangered Species Act 171 EU means the European Union 172 EUP means experimental use permit 173 FDA means the Food and Drug Administration 174 FIFRA means the Federal Insectic ide, Fungicide and Rodenticide Act 175 FFDCA means the Federal Food Drug and Cosmetic Act 176 FQPA means the Food Quality Protection Act 177 FWS means the United States Fish and Wildlife Service 178 HHS means the United States Departm ent of Health and Human Services 179 HSRB means the Human Studies Review Board 180 ICR means Information Collection Request 181 ILSA means International Life Sciences Institute 182 K d means soil partition coefficient 183 K oc means soil organic carbon-water coefficient 184 K o w means octanol-water partition coefficient 185 MOR means magnitude of the residue 186 mg/L means milligrams per liter 187 NAICS means the North American Industrial Classification System 188*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 9 of 234 NAS means the National Academy of Sciences 189 NMFS means the United States Na tional Marine Fisheries Service 190 NPDES means National Pollutio n Discharge Elimination System 191 NPRM means Notice of Proposed Rulemaking 192 “NR” means not required 193 OCSPP means EPA’s Office of Chemic al Safety and Pollution Prevention, 194 formerly Office of Polluti on Prevention and Toxics (OPPTS) 195 OECD means Organisation for Economic Cooperation and Development 196 OMB means Office of Management and Budget 197 OPP means EPA’s Office of Pesticide Programs 198 OPPT means EPA’s Office of Pollution Prevention and Toxics 199 OSHA means Occupational Safety and Health Administration 200 OW means EPA’s Office of Water 201 PPCP means pharmaceuticals a nd personal care products 202 PEL means permissible exposure limit 203 ppb means parts per billion 204 ppm means parts per million 205 PPE means personal protective equipment 206 PRA means the Paperwork Reduction Act 207 PRIA means the Pesticide Registration Improvement Act 208 POTW means publicly owned treatment works 209 QSAR or (Q)SAR means quantitative structure-activity-relationships 210 “R” means required 211*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 10 of 234 RAC means raw agricultural commodity 212 RED means Reregistration Eligibility Decision Document 213 RFA means the Regulat ory Flexibility Act 214 RfC means Reference Concentration 215 RfD means Reference Dose 216 ROC means residue of concern 217 RQ means risk quotient 218 SAP means the FIFRA Scientific Advisory Panel 219 SAR means structure-activity-relationships 220 SBREFA means the Small Business R egulatory Enforcement Fairness Act 221 TGAI means technical grade active ingredient 222 TTC means threshold of toxicological concern 223 TEP means typical end-use product 224 TLV means threshold limit value 225 WET means whole effluent testing 226 WOE means weight-of-evidence 227 WQC means Water Quality Criteria 228 WQS means Water Quality Standards 229 WWTP means wastewater treatment plant 230 USDA means United Stated De partment of Agriculture 231 III. History of this Rulemaking 232 A. Background 233*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 11 of 234 EPA’s data requirements for pesticides were first published in 1984. Those 234 data requirements were primarily influenced by agricultural uses. Since then, new 235 risk concerns have been identified, and EPA ’s statutory mandates for pesticide 236 registration under FIFRA and tolerance- setting under the FFDCA were amended 237 in 1996 to require EPA to update the scientif ic underpinnings of risk assessments. 238 The Agency must now perform more in-depth risk analyses, such as aggregate 239 and cumulative risk assessments. 240 On October 26, 2007, EPA promulgat ed final rules updating the data 241 requirements for conventional pestic ides (72 FR 60934), and biochemical 242 pesticides and microbial pesticides ( 72 FR 60988). The rule development 243 process for part 158, subpart W used t he updated conventional pesticides data 244 requirements as the starting point while considering the case-by-case data 245 requirement decisions made over the years of registering antim icrobial pesticide 246 products. Four of the other subparts in part 158, promul gated in 2007, also apply 247 to antimicrobial pesticides (see 40 CFR 158.1). Those four subparts are: 248

 Subpart A: General Provisions 249

 Subpart B: How to Use Data Tables 250

 Subpart C: Experimental Use Permits 251

 Subpart D: Product Chemistry 252 As part of promulgating those final rules, on October 24, 2007, (72 FR 253 60251) EPA preserved the or iginal part 158 data require ments (promulgated in 254 1984), by redesignating them as part 161, to provide continued regulatory 255 coverage for antimicrobial pesticides unt il the Agency could promulgate a final 256*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 12 of 234 regulation for antimicrobial pesticides. This final rule finishes the promulgation of 257 a final regulation for antimicrobial pestici des. Accordingly, EPA is also revoking 258 part 161 today. 259 B. Discussion of the October 8, 2008 Notice of Proposed Rulemaking (NPRM) 260 EPA published an NPRM on October 8, 2008, (73 FR 59382) proposing to 261 establish data requirements specific to t he registration of antimicrobial pesticide 262 products in 40 CFR part 158, subpart W. The closing date of the 90–day 263 comment period for the NPRM was Januar y 6, 2009. The comment period was 264 extended to April 6, 2009, to allow st akeholders additional time to assess the 265 impact of the proposed revisions on their particular situations and submit their 266 comments. In addition, EPA convened a public workshop in Arlington, Virginia, to 267 explain the provisions of the NPRM on November 6, 2008. The proposed rule, 268 the notice of the extension of the comm ent period, the notice of the public 269 meeting, the presentations used at the public meeting, the comments submitted, 270 and EPA’s Response to Comments Document are available to the public at 271 http://www.regulations.gov (see docket EPA-HQ-OPP–2008–0110). 272 C. Comments Submitted to EPA. 273 During the public comment peri od, EPA received comments on the 274 proposed part 158, subpart W regulations fr om 29 entities. The breakdown of the 275 origin of the comments is as follows: 276

 Antimicrobial Industry – 15 277

o Lanxess Corporation 278

o S.C. Johnson & Sons, Inc. 279*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 13 of 234 o Scientific and Regulato ry Consultants, Inc. 280

o Antimicrobial Exposure Joint Venture (AEJV) 281

o Consumer Specialty Produc ts Association (CSPA) 282

o Ecolab Inc. 283

o ISSA 284

o The Clorox Company 285

o Reckitt Benckiser 286

o Mason Chemical Company 287

o Proctor & Gamble 288

o Dow Chemical Company 289

o Johnson Diversey 290

o Troy Corporation 291

o American Chemistry Council (ACC) 292

 Non-Governmental Or ganizations (NGOs) – 3 293

o Environmental Working Group 294

o Humane Society 295

o Beyond Pesticides 296

 Other – 3 297

o CropLife America 298

o Innovation and Reform Group 299

o Alternative Testing Working Group 300

 Foreign Government Entity - 1 301

o Health Canada 302*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 14 of 234  Water Agencies – 7 303

o Hampton Roads Sanitation District 304

o California Associati on of Sanitation Agencies 305

o National Association of Clean Water Agencies 306

o San Francisco Department of the Environment 307

o Sanitation Districts of Los Angeles County 308

o Tri-Tac 309

o California Stormwater Quality Association 310 There were also late comments from ACC, received at meetings held at 311 EPA in Arlington, VA on December 2, 2009, and June 14, 2010. Most recently, at 312 a meeting on May 17, 2011, and in a le tter dated June 17, 2011, both ACC and 313 CSPA provided additional late comments. The presentation materials and EPA’s 314 summary of the meetings, and the lette r with attachments are included in the 315 docket at http://www.regulations.gov . The late comments submitted by ACC 316 and/or CSPA were not new comments, but rather re-statements of issues 317 presented in their original co mments submitted to EPA. 318 A late comment cosigned by the Ph ysicians Committee for Responsible 319 Medicine, the Humane Society Internationa l, and People for the Ethical Treatment 320 of Animals was submitted on September 1, 2010. This late comment did contain 321 several new issues, which were addr essed by adding the additional comments 322 and responses to the toxicology sect ion of the Response to Comments 323 Document. 324*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 15 of 234 EPA carefully reviewed all comments submitted. The Response to 325 Comments Document is in the docket at http://www.regulations.gov . As 326 previously discussed, the Response to Comments Document contains the 327 rationale for the changes that were made from the proposed rule to the final rule, 328 in response to submitted comments. Similar comments are grouped together. 329 EPA selected the most signific ant of the comments, such as those that impacted 330 the changes from the proposed ru le to the final rule, for inclusion in Units IV to 331 XXII of this final rule. 332 D. This Final Rule 333 1. In general. This final rule reflects updates and revisions to part 161, in 334 many cases by codifying the case-by- case data requirements decisions made 335 over the years to help apply the agricul turally-based 1984 data requirements to 336 antimicrobial pesticide products. The ant imicrobial data requirements are being 337 added to part 158, subpart W. Part 161 is be ing removed. This final rule will 338 further enhance the Agency's ability to make regulatory decisions about the 339 human health, and environmental fate and effects of antimicrobial pesticide 340 products. 341 Based on comments received, EPA re vised the proposed data tables. 342 EPA’s Response to Comments Document is in the docket at 343 http://www.regulations.gov . That document contains the rationale for the changes 344 that were made from the pr oposed rule to the final rule, in response to submitted 345
comments. 346*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 16 of 234 Eleven new data requirements are being codified today. As discussed in 347 the preamble to the proposed rule ( 73 FR 59387), a “new” data requirement 348 “means that the data requirement has never been required or has rarely been 349 required on a case-by-case basis, and has not been routinely considered during 350 the Agency’s evaluation of the data needed fo r the purpose of risk assessment.” 351 Eight new data requirements that we re proposed in 2008 and are now being 352 codified are: Developmental neurotoxici ty; immunotoxicity; photodegradation in 353 soil; soil residue dissipation; ready biodegradability study; porous pot study; 354 activated sludge sorption isotherm st udy; and modified activated sludge, 355 respiration inhibition test. The devel opmental neurotoxicity and immunotoxicity 356 tests are new compared to part 161, but were added for conventional pesticides in 357 the 2007 amendments to part 158. The photodegradation in soil study was not 358 previously required for wood preservatives. The other four st udies are unique to 359 antimicrobials. 360 Since the proposed rule, based on comments received, three new data 361 requirements are also being added: Simulati on tests to assess the 362 biodegradability of chemicals in dischar ged wastewater, simulation test – aerobic 363 sewage treatment: activated sludge units , and nature of the residue on surfaces. 364 Additionally, this final rule: 365

 Codifies data requirements/use pattern combinations that were not codified 366 in part 161, but have typically been required to register an antimicrobial pesticide 367 product. 368*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 17 of 234  Provides improved definitions for ant imicrobial pesticides used for public 369 health and nonpublic heal th purposes. 370

 Codifies data requirements to det ermine risks to waste water treatment 371 plants (WWTPs) and the potential for mo vement of antimicrobials and their 372 degradates from the indoor environment to the outdoor envir onment via effluent 373 discharge from a publically ow ned treatment work (POTW). 374 The data requirements promulgated today identify the types of information 375 that EPA needs to determine whether a pes ticide product should be registered, 376 and make decisions regarding tolerances or tolerance exemptions for pesticide 377 residues in food. Subpart W includes a se ries of tables and r egulatory text that 378 mirrors the data requirements for convent ional pesticide. However, subpart W 379 establishes specific data requirements for each scientific discipline (except 380 product chemistry) for antimic robial pesticides. As expl ained in Unit IIIA., subpart 381 D to part 158, which contains the product chemistry data requirements for 382 conventional pesticides, also applies to ant imicrobials. The order of subpart W 383 also mirrors that of the larger part 158. As such, the following data requirements 384 categories are included in detail in part 158, subpart W: Pr oduct performance, 385 hazard/toxicity (both human health and ecological toxicity), exposure (both 386 application and post-application human ex posures), residue chemistry, and 387 environmental fate requirements. 388 EPA is also codifying 12 antimicrobial use patterns, as described in the 389 proposed rule (73 FR 59389-90, October 8, 2008). As part of today’s action EPA 390*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 18 of 234 has developed and will shortly post on the Agency’s website an Antimicrobial Use 391 Site Index to provide additional information about these use patterns. 392 As promulgated, subpart W is intended to improve the scientific basis for 393 antimicrobial pesticide decisions. Thes e efforts are expected to help protect 394 human health and the environment by pr oviding an up-to-date scientific 395 framework for identifying and assessing the ri sks of antimicrobial pesticides sold 396 or distributed in t he United States. 397 2. Changes to the proposed rule. In response to comments, EPA has 398 made numerous changes to the proposed rule in crafting the final rule 399 promulgated today. The most signific ant changes are summarized below. 400 i. Alternatives to the porous pot study. With regard to the porous pot study 401 in the final Environmental Fate Data R equirements Table in § 158.2280, EPA is 402 adding two simulation studies that can se rve as an alternative to the porous pot 403 study. This change was based on a comment that requested consideration of 404 whether “studies that simulate wastew ater treatment plants (WWTPs) [could] 405 substitute for [the porous pot study ].” (ACC Comment in the docket at 406 http://www.regulations.gov ; document EPA-HQ-OPP-2008-0110-0088.9; 407 Appendix H, entitled “C omments on Proposed Data Requirements for 408 Environmental Fate” p. 5). Additi onally, in the commenter’s suggested 409 environmental fate data requirements table (p . 11), instead of giving the title of the 410 study as “Porous Pot,” the commenter wr ote “Simulated WWTP; e.g., Porous Pot 411 Study.” 412*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 19 of 234 EPA agreed with the comment er and identified two ot her studies: The 413 biodegradation in activated sludge study as described in the OPPTS guideline 414 entitled “Simulation Tests to Assess t he Biodegradability of Chemicals Discharged 415 in Wastewater” and simulation test – aer obic sewage treatment: activated sludge 416 units. This change provides applicants with more flexibility in meeting this data 417 requirement. EPA’s rationale is described in Unit XV.A, and for greater detail see 418 response to comment 134.1 in the Response to Comments Document in the 419 docket at http://www.regulations.gov ). Testnote 3 to the fi nal Environmental Fate 420 Data Requirements Table in § 158. 2280 clearly specifies that only one 421 biodegradation study is to be submitted. 422 ii. Trigger for migration study. EPA made changes to the trigger for the 423 migration study in the final Residue Chemistry Data Requirements in § 158.2290. 424 In its proposed rule, EPA “triggered” t he migration study based on anticipated 425 instances such as theoretical (modeled) es timates yielding a risk of concern. One 426 commenter submitted a suggested residue c hemistry data requirements table with 427 a line-item entitled “Nature of residue of surface.” (ACC Comment in the docket at 428 http://www.regulations.gov ; document EPA-HQ-O PP-2008-0110-0088.10; 429 Appendix I, entitled “Comments on Propos ed Data Requirements for Residue 430 Chemistry” p. 7). A di fferent commenter also submitted a different residue 431 chemistry data requirements table, which al so included the same line-item entitled 432 “Nature of residue on surface.” (CSPA Comment in the docket at 433 http://www.regulations.gov ; document EPA-HQ-OPP-2008-0110-0086.2). 434*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 20 of 234 The commenters’ suggestion of requiring a nature of the residue study on 435 surfaces provides a more definitive tri gger for the migration study. EPA is adding 436 a nature of the residue on surf aces study. As specified in testnote 3 to the final 437 Residue Chemistry Data Requirements Tabl e, the results of the nature of the 438 residue on surfaces study will serve as a trigger for determining whether the 439 migration study will need to be performed. EPA considers the commenters’ 440 suggestion to be a valuable addition to the final Residue Chemistry Data 441 Requirements Table in § 158. 2290 that provides more definitive triggers to help 442 define and narrow the instances of higher-tiered testing. 443 iii. Changes to data requirement s for wood preservatives. As discussed in 444 Unit VI.B, EPA’s current practice of determining the data required for a wood 445 preservative product is dependent upon wher e the product is intended to be used 446 (land-only versus land and aquatic). This approach also assumes that diversion 447 does not occur and that wood that is treated for land-only uses does not end up in 448 the water and vice versa. In practice, it is difficult to assure that diversion does 449 not occur. Accordingly, in response to comments, the Agency determined that all 450 treated wood needs to be considered as havi ng the potential to come into contact 451 with surface water. Therefore, for the final Environmental Fa te Table, for the 452 wood preservatives column, the data r equirements for anaerobi c soil metabolism, 453 aerobic aquatic metabolism, and anaer obic aquatic metabolism were changed 454 from “CR” to “R.” Fo r the final Nontarget Organi sm Table, for the wood 455 preservatives column, the data requirements for chronic toxicity testing with fish 456 (fish early-life stage) and aquatic invertebr ate (aquatic invertebrate life-cycle) are 457*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 21 of 234 being changed from “CR” to “R” to provi de chronic data when chronic exposure is 458 expected. With regards to the three acute toxicity tests conducted with the TEP, 459 the “NR” in the wood preservatives column is changed to “CR.” Additionally, EPA 460 will perform a down-the-drain analysis fo r every product with an applicable use or 461 exposure scenario, including wood preservati ves, that has the potential for waters 462 containing antimicrobials to reach a WWTP. Therefore, to perform this analysis, 463 the Agency is requiring data on the biode gradation of a wood preservative and its 464 potential toxicity to WWTP microorgani sms in an activated sludge basin. 465 iv. Changes to data require ments for antifoulants. Antifoulants are 466 released/applied directly to the aquatic environment. These products are often 467 manufactured to be persistent, and because of the continuous release process, 468 some of the active ingredient is likely to be transferred to the bottom of the water 469 column, and then be adsorbed to the sedim ent. Therefore, EPA is changing, in 470 the final Environmental Fate Data Requi rements Table, the “CR” for the aquatic 471 sediment study for the antifoul ant paint and coatings column to “R.” With regards 472 to the three acute toxicity tests conducted with the TEP, the “NR” in the antifoulant 473 paint and coatings column is changed to “ CR.” Also, to perform a down-the-drain 474 analysis, the Agency is requiring data on the biodegradation of an antifoulant and 475 its potential toxicity to WWTP microorgani sms in an activated sludge basin. 476

v. Non-dietary ingestion. EPA proposed to require this post-application 477 exposure study. However, EPA agrees that instead of requiring this study, it is 478 more likely that EPA would model this r oute and pathway of ex posure using inputs 479*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 22 of 234 from available and reliable published resear ch. Therefore, EPA has removed this 480 data requirement from the final Po st-Application Exposure Table. 481 vi. Re-structuring of proposed toxico logy and residue chemistry data 482 requirement tables. 483 In the proposed rule, for the toxicology data requirements table, EPA separated 484 those use patterns needing more toxicology data from those needing less 485 toxicology data using a terminology de scribed as high or low. Based on 486 comments received, in this final rule, EPA is now using a food/nonfood approach 487 with some similarities to that of t he toxicology data requirements table for 488 conventional pesticides to distinguish t he use patterns that need more toxicity 489 data from those that need less. T he food-use column and the nonfood-use 490 column are split into subcolumns to ex plain which food-uses or nonfood-uses 491 require more data, and which require less. This modification of the food/nonfood 492 approach delineates the specific data requirement needs for antimicrobial 493 pesticides. 494 For the final Residue Chemistry Data Requirements Table, EPA has 495 adopted the commenters’ suggestion for a ti ered format. After review of the 496 commenter’s suggested tables, EPA belie ves the commenters’ suggested tiered 497 approach is more suitable to antimicr obials than that proposed by EPA. 498 vii. Change in terminology. The commenters’ asserted that the use of 499 terms such as” high” or “low” as a m eans of tiering was insupportable, and an 500 “unsubstantiated assignment of exposure categories” ( ACC Comment in the docket 501
at http://www.regulations.gov ; document EPA-HQ-OPP-2008-0110-0088.1 p. 21 and 502 22). EPA continues to believe that the use of “high” and “low” categories of 503*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 23 of 234 exposure defined by the antimicrobial use patterns are a valid method for identifying 504 those exposures that have greater exposure and those that have less. Based on its 505 experience, EPA understands which use patterns require more data. However, EPA 506 can achieve the same result without the use of the terms “high” or “low.” Therefore, 507
b ased on comments received, EPA notes that it is no l onger using the terms “high 508 human exposure” and “low human exposur e” as table headers for the final 509 Antimicrobial Toxicology Data Requirements Table. Sim ilarly, EPA is no longer 510 using the terms “high environmental expo sure” and “low environmental exposure” 511 as table headers for the final Antimicrobi al Nontarget Organism, the Nontarget 512 Plant Protection, or the Environmental Fa te Data Requirements Table. However, 513 EPA also notes that terms such as “h igh human exposure, “low human exposure, 514 “high environmental exposure” and “low environmental exposure” can be 515 appropriate when discussing a particular ant imicrobial use. A statement that a 516 particular use results in, for example, “high environmental exposure” provides 517 information and alerts the reader that more data are likely to be needed, rather 518 than less data. 519 IV. Scope of the Rule 520 This rule establishes a separate listi ng in Title 40 of the Code of Federal 521 Regulations (CFR) for EPA’s data requi rements under FIFRA and FFDCA section 522 408 for antimicrobial pesticide uses. Al though the rule is tailored to the unique 523 characteristics of antimicrobial pestic ides, it builds upon the existing data 524 requirements imposed in 1984 on all pes ticides and the 2007 amendments to 525 those requirements pertaining to conventio nal pesticides. Both sets of data 526 requirements – conventional and antimicrobi al – are designed to provide EPA with 527*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 24 of 234 the information needed to make the r equired regulatory determinations under 528 FIFRA and FFDCA section 408. FIFRA pr ovides that a pesticide may not be 529 registered for sale, distribution, and us e unless “it will perform its intended function 530 without unreasonable adverse effects on the environment . . . .” [7 U.S.C. 531 136a(c)(5)(C)]. FIFRA defines “unr easonable adverse effects on the 532 environment” as both “any unreasonable ri sk to man or the environment” and “a 533 human dietary risk . . . inconsistent wit h the standard under se ction 408 of the 534 [FFDCA]” [7 U.S.C. 136(bb)]. FFDCA section 408 directs that EPA shall not 535 establish a tolerance permitting pesticide residues in food unless EPA determines 536 that the tolerance is “saf e” [21 U.S.C. 346a(b)(2)(A)(i) ]. “Safe,” under FFDCA 537 section 408, is defined as “a reasonable certainty that no harm will result from 538 aggregate exposure to the pesticide chemic al residue, including all anticipated 539 dietary exposures and all other exposures for which there is reliable information” 540 [21 U.S.C. 346a(b)(2)(A)(ii)]. In making safety determinations, EPA is required to 541 consider aggregate and cumulative exposur es from pesticides and other related 542 substances and multiple factors specifica lly related to the protection of children 543 [21 U.S.C. 346a(b)(2)(C) and (D)]. 544 Under FIFRA, EPA has required “[s] ubstantial amounts of data on the 545 pesticide, its composition, toxicity , potential human exposure, environmental 546 properties, and ecological effects, as well as information on its product 547 performance (efficacy) in certain cases” (73 FR 59384, October 8, 2008). Since 548 1984, EPA has had codified FIFRA data r equirements mandati ng data on, among 549 other things, the toxicity hazards from ingestion of pes ticides and exposure levels 550*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 25 of 234 of pesticide residues in food (Ref. 1) . With the passage in 1996 of the Food 551 Quality Protection Act, [Public Law 104-170, 110 Stat. 1489 (1996)], which added 552 the expanded safety standard in FFDCA section 408 described above, EPA’s data 553 needs have expanded. As noted in the preamble to the proposed rule, “[t]he 554 combination of aggregate and cumulative exposure assessments required by 555 FFDCA section 408 increases the natur e and scope of EPA’s risk assessment, 556 and potentially increases the types and am ounts of data needed to determine that 557 the FFDCA safety standard is met” (73 FR 59385, October 8, 2008). Moreover, 558 with the explicit linkage in FIFRA between the FIFRA and FFDCA section 408 559 safety standards (also added by FQPA), “[t]he data required to support a 560 determination of ‘reasonable certainty of no harm’ under FFDCA are an integral 561 part of the data needed for an ‘unreasonable adverse effects’ determination under 562 FIFRA” [Id.; see 72 FR 60934 (October 26, 2007) (recodifying part 158 data 563 requirements under the author ity of both FIFRA and FFDCA section 408)]. This 564 rule establishing specific data requirem ents for antimicrobial pesticides is 565 designed to capture the broad range of data needed to assess the safety of 566 pesticides under the standards of both FIFRA and FFDCA section 408. 567 The ACC Biocides Panel and other co mmenters, however, have claimed 568 that the scope of the proposed rule ex ceeds the EPA’s stat utory authority 569 because EPA is asserting “ jurisdiction under FIFRA over some antimicrobial food 570 uses where, in the Panel’s view, the statutory scheme provides exclusive jurisdiction 571 to FDA” (Food and Drug Administration) (ACC Comment in the docket at 572 http://www.regulations.gov ; document EPA-HQ-OPP-2008-0110-0088.1 p. 31). 573 Although the ACC Biocides Panel acknowledges that these uses are properly 574*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 26 of 234 regulated by EPA as “pesticides” under FIFRA, the Panel argues that “EPA’s 575 responsibility for such use[s] is to ev aluate whether the antimicrobial meets the 576 standard for registration under FIFRA, taking into account FDA’s existing regulatory 577 finding [under FFDCA section 409]. . . . EPA does not have the authority under 578 either FIFRA or FFDCA to review or change the terms of the FDA approval.” (ACC 579 Comment in the docket at http://www.regulations.gov; document EPA-HQ-OPP580 2008-0110-0088.1 p.33). In essence, the Panel is asserting that for these 581 antimicrobial uses, EPA is without authority or jurisdiction under FIFRA to evaluate, or 582 require data on, the level of risk from dietary exposure to the antimicrobial – where 583 FDA has evaluated the safety of the use of the substance under section 409. As a 584 basis for this argument, the ACC Biocides Panel points to the Antimicrobial 585 Regulation Technical Corrections Act (A RTCA), [Public Law 105-324, in 1998], 586 which divided FFDCA jurisdiction between EPA and FDA with respect to 587 antimicrobials. The Panel further ar gues that EPA is wrong to rely on FIFRA 588 section 2(bb)’s inclusion of the FF DCA section 408 safety standard in the 589 definition of “unreasonable adverse effect s” as authority for requiring data on 590 antimicrobial uses falling under FDA’s FF DCA section 409 jurisdiction. Labeling 591 EPA’s interpretation of FIFRA section 2( bb) in the proposed rule as “new,” the 592 ACC Biocides Panel claims that E PA has contradicted its “long-standing” 593 interpretation of this provision. 594 The ACC Biocides Panel fundamenta lly misunderstands EPA’s statutory 595 authority under FIFRA to require data pertain ing to dietary risk from pesticides. 596 EPA’s authority to regulate pesticides under FIFRA with r egard to their dietary risk 597 is derived from FIFRA not the FFDCA. Under FIFRA, EPA is charged with 598*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 27 of 234 protecting the public from “unreasonable adverse effects on the environment.” As 599 noted above, FIFRA in section 2(bb) defines “unreasonable adverse effects” in the 600 first instance as “any unreasonable risk to man . . . .” [7 U. S.C. 346(bb)]. This 601 broad standard clearly encompasses any unreasonable dietary risk. EPA’s 602 authority to regulate pesticides under FI FRA on the basis of dietary risk is 603 explicitly reinforced by the second par t of the unreasonable adverse effects 604 standard which directs EPA to evaluate “h uman dietary risks” from “pesticides” 605 under the safety standard in FFD CA section 408. [Id.] 606 Nothing in FIFRA or the FFDCA limits or constrains EPA’s authority or 607 jurisdiction to regulate pesticides based on dietary risk under FI FRA section 2(bb). 608 The FIFRA section 2(bb) standard is i ndependent from the sa fety standard under 609 FFDCA section 409. Further, any findi ng by EPA under FIFRA that considers 610 dietary risk would not “change the terms of a FDA approval;” rather, it would 611 simply be a determination as to whether the separate FIFRA regulatory standard 612 had been met. Finally, contrary to the ACC Biocides Panel’s contention, the 613 adjustment by the ARTCA of EPA’s and FD A’s jurisdiction under FFDCA sections 614 408 and 409 over antimicrobials does not affe ct EPA’s jurisdiction or authority with 615 regard to dietary risks of pesti cides under FIFRA. In fact , as explained below, not 616 only did the ARTCA not amend FIFRA sect ion 2(bb) but Congress in the ARTCA 617 took the unusual step of expressly disavo wing any intent to narrow the scope of 618 EPA’s authority under FIFRA. 619 The ARTCA was follow-on legislation to the major 1996 FFDCA 620 amendments which, among other thi ngs, changed EPA and FDA jurisdiction 621*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 28 of 234 under FFDCA sections 408 and 409. Prio r to 1996, section 408 of the FFDCA, 622 which is administered by EPA, only applied to “pesticide chemicals” that were 623 defined as FIFRA “pesticides” “used in the production, storage, and transportation 624 of raw agricultural commodities” [21 U. S.C. 321(q) (1994)]. FIFRA pesticide 625 residues in food not falling within this prov ision (i.e. FIFRA pesticides used later in 626 the food production process than the grow th of raw agricultural commodities) 627 came under section 409 of the FFDCA as food additives [ See 21 U.S.C. 321(s), 628 348 (1994)]. FDA administers the estab lishment of food addi tive regulations 629 under FFDCA section 409. M any antimicrobial pesticides used in conjunction with 630 the manufacturing and processi ng of foods, at that time , were regulated as food 631 additives. This division of legislativ e authority was changed by the FQPA in 1996. 632 The FQPA amended the definition of “pesticide chemical” in the FFDCA to make it 633 co-terminous with the definition of a “pes ticide” in FIFRA by deleting the language 634 restricting pesticide chemicals to those pesticides used in the production of raw 635 agricultural commodities. Correspondingl y, the FQPA also excluded “pesticide 636 chemicals” from the defin ition of a “food additive” [Public Law 104-170 § 402, 110 637 Stat. 1489, 1513 (1996)]. This change had t he effect for FFDCA purposes of 638 bringing all FIFRA pesticides under FF DCA section 408. Not only did Congress 639 consolidate regulation of all pesticide re sidues in FFDCA section 408 but it also 640 amended FIFRA to insure that the new safety standard in FFDCA section 408 641 was part and parcel of the FIFRA registra tion standard for pesticides resulting in 642 residues in food [7 U.S.C. 136(bb)(2)]. S pecifically, as noted above, in section 643 2(bb)(2), Congress defined an “unreasonable adverse effect on the environment” 644*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 29 of 234 under FIFRA as “a human dietary risk from residues that result from a use of a 645 pesticide in or on any food inconsistent with the standard under section 408 of the 646 Federal, Food, Drug, and Cosm etic Act [21 U.S.C. 346a].” 647 In 1998 in the ARTCA, Congress modifi ed slightly its FFDCA decision to 648 consolidate all pesticide chemical resi dues in foods under FFDCA section 408. 649 ARTCA amended the definition of “pesticide chemical” in FFDCA section 201 to 650 exclude certain antimicrobial substances from the coverage of the definition [ See 651 21 U.S.C. 321(q)]. More specifically, with certain qualifications, the ARTCA 652 excepted, from the definitio n of pesticide chemical, substances that are FIFRA 653 pesticides and are “applied for [an antimicrobial] use on food, or the substance is 654 included for such use in water that comes into contact with food, in the preparing, 655 packing, or holding of the food for commercial purposes.” [21 U.S.C. 656 321(q)(1)(B)(i)]. In addition, ARTCA excepted subst ances from the definition of 657 pesticide chemical that are food contac t substances, as defined in section 658 409(h)(6) of the FFDCA, based on certain ci rcumstances related to their use. 659 These antimicrobial substances were now no longer considered “pesticide 660 chemicals” under the FFDCA but fell under t he definition of “food additive.” That 661 had the effect of shifting the residues resulting from t hese antimicrobial 662 substances from FFDCA section 408 to FFDCA section 409 and shifting agency 663 jurisdiction under the FFDCA over the sa me from EPA to FDA. Importantly, 664 Congress, in ARTCA, did not amend FIFRA to remove these uses of antimicrobial 665 substances from the definition of “pesticide” under FIFRA and left unchanged 666 FIFRA section 2(bb)(2) which mandates t hat the section 408 safety standard is 667*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 30 of 234 part of FIFRA’s unreasonable adverse effe cts standard as to FIFRA “pesticide” 668 residues on food. Thus, EPA retained FIFRA jurisdiction over these antimicrobial 669 substances (because they remained FIFRA “pesticides”) while FDA re-acquired 670 FFDCA jurisdiction over them under FFDCA section 409 (because they were 671 removed from the definition of “pesticide ch emical”). To make clear its intent on 672 EPA’s FIFRA jurisdiction, the ARTCA in cluded the following express disavowal 673 which was inserted into the FFDCA defin ition of “pesticide chemical:” 674 With respect to the definition of the term ‘pesticide’ that is 675 applicable to the Federal In secticide, Fungicide, and 676 Rodenticide Act, this clause [excluding certain 677 antimicrobial substances fr om the FFDCA definition of 678 “pesticide chemical”] does not exclude any substance 679 from such definition” [21 U.S.C. 321(q)(1)(B)]. 680 Since its passage, EPA has interpret ed the ARTCA according to its plain 681 language, excluding the desig nated antimicrobial substances from the coverage 682 of FFDCA section 408 but continuing to regulate those antimic robial substances 683 that qualify as FIFRA “pesticides” under FIFRA and requiring that, when those 684 antimicrobial pesticides result in residues in food, the risks from such residues be 685 consistent with the safety standard in FFDCA section 408. After all, FIFRA 686 section 2(bb)(2), on its face, applies to FIFRA “pesticides” and not FFDCA 687 “pesticide chemicals.” Any other result would be directly contrary to Congress’ 688 dictate that it was not ex cluding any substances from the FIFRA definition of 689 “pesticide.” Accordingly, it is well wit hin EPA’s FIFRA authorit y to require that 690 data be submitted on pesticides to determine if those pesticides meet the FFDCA 691 section 408 safety standard, whether or not those pesticides come within the 692 definition of a FFDCA “pesticide chemical,” so long as the use of those pesticides 693*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 31 of 234 results in residues in food. On t he other hand, the ACC Biocides Panel’s 694 approach would involve amendi ng the language of section 2(bb)(2) in a manner 695 specifically rejected by the Congress when it passed ARTCA. 696 There is no basis for the ACC Biocide Panel’s claim that EPA’s 697 interpretation of FIFRA section 2(bb)(2) is “new.” The best evidence of the 698 consistent and long-held nature of EPA’ s interpretation are the numerous 699 submissions to the Agency from the Panel ( and others) over t he last 10 years 700 disputing EPA’s plai n language approach to FIFRA secti on 2(bb)(2). (Refs. 2, 3, 701 4, 5, 6, 7, 8, 9, and 10) 702 V. Discussion of Several Issues Repeated Throughout Most Comments 703 In evaluating the comments receiv ed on proposed part 158, subpart W, 704 EPA noted that four specific comments were routinely repeated throughout most 705 of the entire set of comments. 706 A. Differentiating the Review of Antimicrobials 707 1. Comment. EPA received several comment s noting that FIFRA section 708 3(h)(3)(A)(ii) specifies that EPA must diffe rentiate the review of antimicrobial 709 pesticides from that of other pesticides. 710 2. EPA’s Response . FIFRA section 3(h)(3)(A )(ii) specifies, among other 711 things, that, in proposed regulations to accelerate and improve the review of 712 antimicrobial pesticide products, EPA sh all define the various classes of 713 antimicrobial use patterns, differentiate the types of review undertaken for 714 antimicrobial pesticides, conform the degree and type of review to the risks and 715 benefits presented by antimicrobial pesti cides, and ensure that the registration 716*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 32 of 234 process is sufficient to maintain antim icrobial product efficacy. While those 717 elements apply to a proposed rulemaking that the Agency published on 718 September 17, 1999 (64 FR 50671), the Ag ency has been mindful of those same 719 elements in its development of part 158, subpart W. As applied to antimicrobial 720 product registration actions, differentiati on refers to the tailoring of data 721 requirements so that they are responsive to considerations about the antimicrobial 722 products to which they relate. In prac tice, differentiation means that the data 723 requirements applied to antimicrobials are designed to respond to the special or 724 unique needs of antimicrobi als such as the nature of the products, their 725 ingredients, their uses, etc. Differentiation or tailori ng does not mean that the 726 resulting data requirements for antimi crobials will necessarily be comprised of 727 more, less, or the same number and type of data requirement s as required for 728 other types of pesticides such as conventional pesticides. 729 For example, the residue chemistr y data requirements for conventional 730 pesticides focus on the application of agric ultural pesticides to crops growing in 731 the fields. However, the residue chemistr y data requirements for antimicrobials, 732 codified today, have been tiered to account for applications that focus not on 733 crops growing in the fields (where antim icrobials are rarely used), but instead 734 account for antimicrobial uses, including those that result in residues on food 735 more indirectly, such as from use as sanitizers in food processing plants. The 736 overall impact is to require fewer studies since the tiering used for the 737 antimicrobial residue chemistry data requi rements table is structured differently, 738 and there are fewer “R” studies and most st udies are “CR.” However, there are 739*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 33 of 234 two residue chemistry data requirements (migration and nature of the residue on 740 surfaces) for antimicrobials that are not included in the conventional residue 741 chemistry data requirements table because they reflect the unique use sites for 742 antimicrobials; see Unit XVI for addi tional discussion. Ecotoxicity and 743 environmental fate data requirement s provide another example of the 744 differentiation of data requirements between antimicrobial s and conventional 745 pesticides. While conventional or biochem ical/microbial pesticides are often used 746 outdoors, and are deliberat ely placed/spread in the environment, most 747 antimicrobials are used indoor s. As discussed in the preamble (73 FR 59406), 748 previously EPA had assumed that many of the indoor uses went down-the-drain 749 to a waste water treatment plant (WWT P), where the WWTP processes would 750 mitigate environmental concerns. T herefore, in 1984, EPA required basic 751 ecotoxicity and environmental fate dat a for conventional pesticides but made 752 these types of data conditional for indoor uses such as antimicrobials based on 753 whether antimicrobial-specific data indi cated that environmental exposure may 754 occur. However, as discussed in t he proposed rule (73 FR 59407), in recent 755 years there have been detections of antimicrobial chemicals (with indoor uses) in 756 waterbodies. These antimicrobials are moving into the environment via treated 757 effluent. Therefore, EPA is requiring for antim icrobials a specific tiered-set of data 758 to evaluate the likelihood of environmental exposure to antimicrobials that may 759 reach a WWTP, as a result of being washed down the dr ain via leachates, 760 rinsates, and flushes. These data evaluat e whether antimicrobials are likely to 761 survive the treatment processes at a ty pical WWTP, and thus would be present in 762*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 34 of 234 the WWTP effluent. Antimicrobials that do survive the treatment processes have 763 the potential to end-up in the terrestrial or aquatic environments and higher-tiered 764 ecotoxicity and environmental fate data ar e only triggered for t hese antimicrobials. 765 766 Thus, differences in data requirement s stem directly from the inherent 767 differences in the nature of the particular type of pesticide's use. Even with such 768 differentiation or tailoring, there is a gener al core of data requirements which may 769 be expected to be applicable to any kind of pesticide product, such as product 770 chemistry data requirements. EPA’s ul timate goal with its antimicrobial data 771 requirements is to create a body of dat a requirements which produce sufficient 772 information for Agency to consider and use in making its statutorily-required 773 determinations regarding the risks and benefits, where applicable, of antimicrobial 774 pesticides. The differentiation or tailoring of the antimicrobial data requirements is 775 instrumental in accomplishing that goal. 776 B. Rewrite and Repropose the Rule 777 Several commenters requested that EPA rewrite and then repropose this 778 rule. Commenters raised three argum ents as to why EPA should repropose. 779 First, the proposed regulation does not cont ain scientifically-based criteria for 780 determining data requirements but inst ead requires that data requirements be 781 determined in case-by-case consultations in which EPA retains “sole discretion” 782 as to the data required. Second, EPA has not disclosed how it plans to use the 783 proposed data in EPA risk assessments. Th ird, affected parties cannot properly 784 evaluate the data requirements without fi nal guidelines on how such studies 785*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 35 of 234 should be conducted. Each of these three arguments are addressed in detail 786 below. 787 1. Comment on scientific ally-based criteria . Several commenters focused 788 on the testnotes to the data requirements tables, and claimed t hat the proposed 789 rule “leaves too many standards and decis ions to the sole discretion of EPA, 790 creating uncertainty and, i nevitability, inconsistency in regulatory decision 791 making.” Too many determinations, t he commenter asserted, are at “EPA’s 792 discretion” because the proposal is vague without clear-cut criteria. Additionally, 793 they argued that there are t oo many places in the test notes where consultation 794 with the Agency is required or the phrase “as determined by the Agency” is used. 795 (One commenter listed 37 instances in whic h the proposal allegedly substituted a 796 mandatory consultation process for regul atory criteria.) According to the 797 commenters, EPA should eliminate most of the consultation requirements and 798 instead, repropose the rule providi ng a clear set of requirements. 799 2. EPA’s response to comment on scientifically-based criteria . Test notes 800 often contain qualitative or quantitative measures for use in determining whether a 801 study is triggered or not. Most frequently th is occurs when there is an initial study 802 that relates to whether subsequent te sting would be needed or not. Not all 803 triggers are easily reduceable to quantit ative measures and EPA believes that 804 qualitative descriptors such as “expected to enter the environment in significant 805 concentrations,” “if repeated dermal exposur e is likely to occur under conditions 806 of use,” and “the use of the pesticide is likely to result in repeated human 807 exposure over a limited portion of the hum an lifespan” provide meaningful criteria 808*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 36 of 234 for determining when a study is triggered. EPA has carefully reviewed each of the 809 37 test notes cited by one commenter and has identified several instances in 810 which clarification of the criteria was appropriate. EPA’s analysis of these 37 test 811 notes and resultant changes are included in response to comment 3 in the 812 Response to Comments Document in the docket at http://www.regulations.gov

. 813 In numerous places the test notes c ontain language stating t hat the criteria 814 would be applied “as determined by the Agency.” Commenters have 815 misinterpreted this as giving EPA the authority to make decisions on factors other 816 than the regulatory criteria in cluded or in its “sole discret ion.” This was not EPA’s 817 intent and, accordingly, EPA has removed all “as determined by the Agency” from 818 all test notes for the fina l antimicrobials rule so there can be no chance of a 819 misunderstanding of how the cr iteria are to be applied. 820 Commenters also asserted that the EPA’s alleged mandatory consultation 821 requirements rendered the test notes meaningless, as EPA would determine 822 whether studies were required in pr ivate based on unspecified factors. EPA 823 disagrees. The commenters have misread the proposed rule language and 824 misunderstood the purpose for consultation. The consultation references were 825 not intended to impose a mandatory consul tation requirement. To the contrary, 826 the references to consultation was an attempt by EPA to signal its willingness to 827 meet with applicants to adapt studies, if nece ssary, to the specif ics of individual 828 antimicrobials. 829 Consultation is a longstanding, commonly used and valuable process in 830 EPA’s Pesticide Program. Applicants often meet with O PP staff on a pre- 831*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 37 of 234 submission basis to review and discuss the adequacy of the available data. OPP 832 believes that such meetings are benefic ial to both EPA and the applicants. In 833 practice, such meetings are very often sought by registrant s and applicants. By 834 encouraging communication and exchange of ideas, such discussions can help in 835 the development of clearer expectations of what must be subm itted in instances 836 where data requirements involve complexiti es. Consultation can result in data 837 that better meets EPA’s needs and sa ves resources for both EPA and the 838 applicant. Depending upon what is intended to be addressed, such meetings do 839 not necessarily need to be held in person, but can be frequently accomplished via 840 tele-conferencing. 841 EPA did not intend its references to c onsultations in the test notes to 842 impose mandatory consultation require ments; neither did EPA intend the 843 consultation references as a means of establishing a different standard for 844 determining if a study is tr iggered. EPA has carefully reviewed all test notes in the 845 antimicrobials final rule and removed all references to consultation from all 846 testnotes for the antimicrobials ru le so there can be no chance of 847 misunderstanding the voluntary nature of consultation. 848 3. Comment on use of data in risk assessment. The commenters also 849 argued that reproposal was necessary because they could not meaningfully 850 comment on the proposal without understand ing how the data would be used by 851 EPA. Specifically, one comment er wrote: “It is not pl ausible for [the commenter] 852 or others to meaningfully comment on the Proposal without the benefit of 853 understanding the risk assessment approaches EPA plans to use, (e.g., human 854*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 38 of 234 and ecological), the ways in which the data requirements will provide information 855 to conduct those assessments and the wa ys EPA will use those risk assessments 856 in making regulatory decisions. 857 4. EPA’s response on use of data in risk assessment. EPA disagrees with 858 this comment for several reasons. Fi rst, how EPA conducts risk assessments and 859 how it uses toxicological, ecological, and exposure data in those risk assessments 860 is well known. Risk assessment is not unique to OPP. The principles used by 861 OPP and, in fact, by EPA are those used by the scientific community in general. 862 OPP follows the processes and procedur es in the many risk assessment 863 guidance documents that have been issued by EPA (see 864 http://www.epa.gov/risk assessment/guidance.htm). The Agency’s exposure and 865 risk assessment procedures have been pres ented in numerous exposure and risk 866 assessments for antimicrobial pesticides. EPA’s assessments reflect the best 867 available data, and the state of the science of exposure and risk assessment 868 models, methods, and procedures. 869 Moreover, OPP’s risk assessment pr ocedures for pesticides are well870 documented. EPA has recently concluded the process of completing 871 Reregistration Eligibility Decision Documents for all pesticides under FIFRA and 872 reassessing all FFDCA pesticide toler ances. This was a very open process 873 involving multiple public comment opportuniti es as to each pesticide. Further, all 874 regulatory decision documents as well as the underlying risk assessments have 875 been made available to the public. EPA has now begun new pesticide reviews 876*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 39 of 234 under the Registration Review program , and that process is equally open and 877 transparent. 878 A second reason why EPA believes this co mment to be misdirected is that 879 the proposed rule does not represent a c hange to EPA’s existing and transparent 880 risk assessment procedures. Rather, the pr oposal is merely designed to tailor the 881 existing data requirements that apply to a ll pesticides in a way that is more 882 specific to antimicrobial pesticides, as well as including some new requirements 883 applicable to antimicrobials. 884 Finally, the comment is without foundat ion because EPA has explained the 885 need for each study and provided backgr ound information on the purpose for 886 which each study would be required. Pa rt 158, subpart B contains an extensive 887 description of the need for and use of submitted studies (40 CFR 158.130). 888 Additionally, as explain ed in the preamble to the antimicrobials proposed rule, 889 EPA relied on the proposed and final rules fo r establishing data requirements for 890 conventional pesticides. As stated in the proposed rule for antimicrobials, the 891 rationales for requiring and/or revising par ticular data requirements were in those 892 rules. 893 With few exceptions, these rationales are also 894 applicable to antimicrobial pesticide chemicals, and 895 as such have not been repeated in today’s proposed 896 rule. Today’s proposal discusses in detail only those 897 revisions that are singularly applicable to antimicrobial 898 pesticides, including antifoulants and wood 899 preservatives.” (73 FR 59384) 900 901*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 40 of 234 Examples of studies applicable to ant imicrobial pesticides and for which a 902 description of the need for t he requirement was included in the preamble to the 903 proposed rule for antimicrobials include the need for: 904

 The 90-day dermal and 90-day inhal ation studies for a heating, 905 ventilation, air conditioning, and re frigeration uses ( 73 FR 59395), 906

 A food migration st udy (73 FR 59404), and 907

 Environmental fate studies to support a down-the-drain assessment 908 (73 FR 59408). 909 One commenter presented several ex amples of what the commenter 910 labeled as EPA’s “ad hoc risk assessment processes.” An ex amination of those 911 examples shows that the commenter is concerned with what it labels as 912 “inconsistency in EPA’s current practice” as to when a dietary risk assessment is 913 needed for antimicrobial pesticides. T he commenter argued that this alleged 914 inconsistent practice shows the “need for stable, transparent guidance on risk 915 assessment to support data requirements re gulation.” EPA does not believe that 916 it has been inconsistent in its risk assessments. Furthermore, EPA does not 917 believe that such “inconsistencies,” if t hey exist, would mean that affected parties 918 could not comment meaningfully on the pr oposed data requirement s. Ultimately, 919 the issue with the data requirements ru le is whether EPA has asked for data 920 needed for determining whether pesticides m eet the relevant statutory safety 921 standards. The fact t hat EPA might have been inconsistent in the past in its 922 determinations with regard to the safety st andard or how it went about assessing 923 whether a pesticide met the safety standar ds (e.g., did EPA need to do a dietary 924*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 41 of 234 risk assessment), does not handicap an affected party in determining whether a 925 proposed data requirement is consistent with the statutory safety standards. To 926 reiterate, the relevant ques tion is not whether EPA has guidance on when dietary 927 risk assessment is needed but whether the proposed data requirements 928 pertaining to dietary risk would require information that are appropriate to EPA’s 929 determination under the applicabl e statutory safety standar ds. To the extent, the 930 commenter is concerned with any particu lar Agency decision regarding when a 931 dietary risk assessment is needed for ant imicrobials, EPA encourages the 932 commenter to raise that concern directly with the Agency in the context of the 933 specific matter causing the commenter concern. 934 This commenter later filed additio nal comments that further developed the 935 argument that reproposal is necessary because EPA allegedly has not clearly 936 defined when a dietary risk assessment is needed. The commenter wrote: “[T]he 937 Proposal does not clearly articulate any standards for determining what uses 938 triggers a food analysis. It has become apparent since the Proposal was issued 939 that the Agency will interpret this regul ation to vastly increase the number of 940 antimicrobials regulated as food use.” (ACC/CSPA letter in the docket at 941 http://www.regulations.gov ; document EPA-HQ-OPP.2008- 0110-0107, p. 2). 942 Further, the commenter then asserts t hat “EPA’s economic analysis does not 943 even attempt to address the increase in the burden on registrants and applicants 944 that this [alleged] expansi on of the need for ‘food contact’ approvals will cause.” 945 (Id.) These additional comments suggest that this commenter is concerned with 946 EPA decisions issued prior to today’s final rule (and, in most cases, prior to 947*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 42 of 234 issuance of the proposed rule) and fears how the final rule may be interpreted in 948 the future. However, it is difficult to determine from these comments whether the 949 commenter is claiming that this alleged “expansion” of food use antimicrobials is 950 effected by any particular language in the proposed rule. To the extent the 951 commenter is arguing that the expansion is caused by EPA’s application of the 952 FFDCA section 408 standard to all antimic robial food uses under FIFRA section 953 2(bb) (whether the use requires clearance under FFDCA secti on 408 or 409), the 954 commenter, as explained in Unit XV I.A, misunderstands EPA’s authority under 955 FIFRA and EPA’s practice as to antimicr obials since the passage of ARTCA. In 956 another place in its recently-filed comment s, the commenter ar gues that the use 957 of the categories of “direct food use” and “indirect food use” “create the potential 958 for almost all antimicrobials to be cons idered as possibly leaving residues on 959 food.” (ACC attachment 1 in the docket at http://www.regulations.gov ; document 960 EPA-HQ-OPP.2008-0110-0108, p. 4) Ho wever, EPA adopted the categories of 961 direct and indirect food use as a way to tier data requirements for residue 962 chemistry and toxicology, not to expand the category of food uses. For a use to 963 qualify as an indirect food use it must result in residues in food and EPA clearly 964 has the authority under FIFRA and the FF DCA to request data on and assess the 965 risk of pesticide residues in food. Despite the commenter’s claims to the 966 contrary, it is not EPA’s int ent to use this data requirements rule as a basis for 967 expanding what antim icrobial uses qualify as dire ct or indirect food uses. 968 Accordingly, EPA’s economic analysis has accurately captured the costs imposed 969 by this rule. 970*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 43 of 234 5. Comment on lack of final guidelines. Finally, commenters argued that 971 reproposal was needed because affected par ties cannot properly evaluate the 972 data requirements without final guideli nes on how such studies should be 973 conducted. 974 6. EPA’s Response on lack of final guidelines. EPA disagrees with this 975 comment: EPA can require submission of a particular study even if no guideline 976 has been provided. The types of data needed for EPA to make a registration 977 decision are clearly identified in its proposed rule. Test ing laboratories routinely 978 conduct these studies, as evidenced by the te st cost data which was available for 979 use in both EPA’s and the commenter’s ec onomic analyses. Final guidelines are 980 available for the majority of tests requir ed, and draft guidelines provide information 981 for the applicant to consider. Since there was an understanding of the types of 982 data EPA proposed to require, the commenter had sufficient information to 983 comment on whether EPA had asked for the data needed for determining whether 984 pesticides meet the relevant statutory safety standards. 985 It is important to keep in mind that, as noted in the proposed rule, new part 986 158, subpart W is “retaining most current data requirement s for antimicrobials. . . 987 and revises other existing data requirements. ” (73 FR 59383) The guidelines that 988 the commenter asserts as not providing su fficient information to permit meaningful 989 comment pertain, for the most part, to these existing data r equirements that are 990 not being modified by this rulemaking. As to the “new” data requirements that are 991 imposed by this rule, the commenter has not specifically explained why interested 992 parties cannot meaningfully comment on these requirements or why a final 993*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 44 of 234 guideline is needed to provide meaningful comm ents on these studies. In fact, as 994 to these “new” studies, OPPTS guidelines ar e available for all ex cept the nature of 995 the residue on surfaces study. For that study, due to the many site- and chemical 996 specific variations, a protoc ol review is required. 997 This commenter later filed additio nal comments stating that “FIFRA 998 requires EPA to issue test guidelines.” (ACC/CSPA letter in the docket at 999 http://www.regulations.gov ; document EPA-HQ-OPP.2008-0110- 0107, p. 4). In 1000 accordance with FIFRA section 3(c )(2)(A), EPA has promulgated data 1001 requirement rules “specifying the kinds of information which will be required to 1002 support the registration of a pesticide.” EPA is not required to issue guidance 1003 explaining how studies that are addressing the data required under the 1004 regulations should be performed. Additio nal information on EPA’s development of 1005 guidelines is in Unit XX. 1006 C. Alternative Testing Paradigms. 1007 1. Comment. A commenter asked how OPP plans to implement the 1008 National Academy of Sciences (NAS)/EPA Vi sion of Toxicity Testing in the 21 st 1009 Century or the Strategic Plan for Evaluating the Toxi city of Chemicals. The 1010 commenter noted that the ru le should be specific in identifying alternative 1011 approaches that EPA will consider. 1012 2. EPA’s Response. In the proposed rule, in Unit XVIII, entitled “Alternative 1013 Testing Paradigms,” EPA discussed its co mmitment to moving towards a more 1014 efficient and refined testing/risk assessment paradigm for antimicrobial pesticide 1015 chemicals. That discussion included the following: 1016*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 45 of 234  OPP’s current thinking on how Stru cture-Activity-Relationships (SAR) 1017 and Quantitative SAR (QSAR or (Q)SAR) m odeling could be used as part of an 1018 integrated approach to hazard and risk a ssessment to support a regulatory 1019 decision-making process for antimicrobial pesticides. 1020

 The evolution of the cu rrent paradigm of animal ( in vivo ) toxicity 1021 testing toward a more integrated ti ered testing approach for antimicrobial 1022 pesticides. 1023

 Development of computational tools for interpreting data from 1024 computational chemistry, high- throughput screening (HTS) and genomic 1025 technologies. 1026

 The EPA-funded reports by the NAS entitled “Toxicity Testing for 1027 Assessment of Environmental Agents” (2006) and “Toxicity Testing in the 21 st 1028 Century: A Vision and a Strategy” (2007). 1029 The NAS recommendations are truly visionary and involve a transformative 1030 paradigm shift in toxicology based largely on the increased use of in vitro 1031 molecular and cellular assays, and comput ational modeling that make testing 1032 faster and less costly, and reduces anima l testing significantly. The new 1033 technologies are expected to help EPA better understand how chemicals perturb 1034 normal biological function(s), and thus identify toxicity pathways. Potential toxic 1035 effects of chemicals coul d then be predicted based on in vitro bioactivity profiles 1036 derived from a chemical’s effects on cellu lar molecules and processes. Thus, the 1037 scientific foundation for this new paradigm is based on linking in vitro effects with 1038 adverse outcomes in vivo , and on computer modeling that extrapolates to 1039*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 46 of 234 predicted responses in whole tissues, organisms and populations based on 1040 realistic human or env ironmental exposures. 1041 EPA is working to develop and evaluate new technologies in molecular, 1042 cellular, and computational sciences to suppl ement or replace the more traditional 1043 methods of toxicity testing and risk assessment (see 1044 http://www.epa.gov/pesticides/sci ence/testing-assessment.html ). Such an 1045 approach begins with consideration of ex posure information along with hazard1046 based hypotheses about the plausible toxico logical potential of a chemical or 1047 group of chemicals based on their physical- chemical properties and their effects 1048 on biological targets in vitro . This information is then combined with computer 1049 modeling to target animal testing to the specific data needed for human health 1050 and ecological risk assessments. 1051 No single new technology will be able to address all situations. However, 1052 by using a suite of tools and approaches in combination, EPA believes it is 1053 possible to improve the hazard and exposure assessments that form the basis for 1054 understanding pesticide chemical risks. It will take time and substantial research 1055 to build this new approach. OPP will inco rporate the new technologies into EPA’s 1056 hazard and risk assessment processes as the technologies are sufficiently 1057 developed and peer reviewed. Development and vetting of this new approach to 1058 chemical management must be accomplishe d while continuing to make pesticide 1059 registration decisions. Eventually, the new technologies should: 1060

 Create a broader suite of compute r-aided methods to better predict 1061 potential hazards and exposures, and to focu s testing on likely risks of concern. 1062*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 47 of 234  Improve the approaches to more tradi tional toxicity te sts to minimize 1063 the number of animals used while expand ing the amount of information obtained. 1064

 Improve OPP’s understanding of toxicity pathways to allow 1065 development of non-animal tests that better predict how exposures relate to 1066 adverse effects. 1067

 Improve the diagnostic biomonitoring and surveillance methods to 1068 detect chemical exposures and identif y causes of toxic effects. 1069 Since the publication of the propo sed rule in October 2008, OPP 1070 announced its strategic direction to move toward an improved testing and 1071 assessment paradigm where in vivo (animal) testing would be targeted to the 1072 most likely hazards of c oncern. OPP envisions an enhanced testing/assessment 1073 paradigm that is a progressive, tiered- testing approach. This paradigm shift 1074 should accrue the following benefits to OPP: 1075

 Ability to evaluate more c hemicals across a broader range of 1076 potential effects in a shorter time frame. 1077

 Potential to increase the feasibi lity of assessing the risks posed by 1078 mixtures. 1079

 Enhanced predictive ability to det ermine whether animal testing is 1080 needed to refine a risk assessment and to inform management decisions. 1081

 Refine and reduce animal testing by maximizing information 1082 obtained from animal studies, and fo cusing on effects of concern. 1083

 Opportunities for improved diagnostic biomonitoring and surveillance 1084 methods to detect chemical exposures and identify causes of toxic effects. 1085*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 48 of 234  Enhance the quality and efficiency of risk assessment and risk 1086 management decisions. 1087 Over the next several years, O PP intends to improve and transform its 1088 approach to pesticide risk management by e nhancing its ability to use integrated 1089 approaches to testing and assessment. The Agency’s work on an integrated 1090 approach means the development of increasingly effective laboratory animal tests 1091 that are designed to maximize the in formation generated about the nature of the 1092 effects being studied. OPP intends to expand its tool box of predictive models. 1093 The new toxicity and exposure approac hes will enhance priority-setting and 1094 screening approaches and theref ore focus Agency and societal resources on 1095 those chemicals with the greatest risk potential. 1096 These advances will be incorporated within a risk assessment framework 1097 of problem formulation, hazard, dose response, exposure assessment, and risk 1098 characterization to support pesticide regist ration decisions. As this framework 1099 evolves, EPA will create pilot progr ams and develop guidance documents to 1100 inform applicants and others of the alternative approaches being used. 1101 It will require many years to realize the NAS vision of a new toxicity 1102 paradigm based on evaluating perturbations in cellular pathways by reliance on 1103 an array of computational and in vitro methods. However, the development and 1104 expansion of certain tools used to guide more intelligent in vivo testing is 1105 anticipated to become avail able in the nearer term ( ≤ 5 years) which includes 1106 (Q)SAR/expert systems, TTCs, and in vitro technologies. As EPA transitions to 1107 the use of these components of intelli gent testing or alternative methods, 1108*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 49 of 234 communication will be essential. Th rough its Pesticid e Program Dialog 1109 Committee, OPP has created a 21 st Century Toxicology/New Integrated Testing 1110 Strategies Workgroup. For information, see 1111 http://www.epa.gov/pesticides/ppdc/testing/index.html

. 1112 Additionally, OPP has and will continue to publicly vet this new approach. 1113 On May 24 – 26, 2011, OPP requested that the FIFRA Scientific Advisory Panel 1114 (SAP) consider and revise a set of sci entific issues related to Integrated 1115 Approaches to Testing and Assessment (IATA) Strategies: Use of new 1116 computational and molecular tools. OPP plans to build on an established 1117 foundation of using a variety of tool s in a tiered testing and assessment 1118 framework by systematically adding new tools and meth odologies, as well as an 1119 advancing understanding of key events in to xicity pathways. OPP requested the 1120 SAP's input on EPA’s plans to maximize use of existing data from similar 1121 compounds, including information from new toxicity hazard computational and in 1122 vitro predictive models, and expo sure modeling to target in vivo toxicity testing 1123 that is necessary to assess and manage chemical risks, appropriately. Two case 1124 studies illustrated the use of these approaches. The SAP Report, once 1125 completed, will be available at 1126 http://www.epa.gov/scipoly/sap/meet ings/2011/052411meeting.html#frn. 1127 VI. Discussion of Key Comments on Antimicrobial Use Patterns 1128 A. Definitions of Use Patterns 1129 1. Comment . The commenter suggested diffe rent use patterns for EPA to 1130 consider. The commenter believes that the use patterns proposed by EPA are not 1131*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 50 of 234 use patterns but descriptions of product types. The commenter suggested six 1132 general use patterns for EPA to consider. These include: 1133

 Indoor industrial (all nonfood); 1134

 Indoor residential/commerci al/institutional nonfood; 1135

 Indoor commercial/institutional food; 1136

 Aquatic areas nonfood; 1137

 Aquatic areas food; 1138

 Material preservative for exempt treated article uses. 1139 2. EPA’s Response. The Agency disagrees that these suggested use 1140 patterns are adequate substitutes for t he proposed use patterns. The use 1141 patterns that EPA proposed provide a reasonable approach for allowing the 1142 Agency to more clearly identify and tailor the data requirements for the different 1143 type of antimicrobial pesticides. In so me cases, that is best accomplished by 1144 using the product type to define the use pattern. 1145 EPA has reviewed the commenters’ de scriptions of their six suggested 1146 general use patterns and has determined th at they do not acknowledge all 1147 potential exposure pathways of antimicr obial pesticides, particularly those 1148 discharged to wastewater as a result of processing and end-use. Although three 1149 of the proposed general use patterns incl ude “indoor” in the name, the exposure 1150 potential for these use patterns is not lim ited to the indoor environment. This is 1151 because these patterns include processe s and end-uses of antimicrobial 1152 pesticides that are discharged to wastewat er, thereby leading to the potential for 1153 microorganisms in WWTPs to be exposed to antimicrobial pesticides and for 1154*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 51 of 234 aquatic organisms to be exposed to antimic robial pesticides in surface water 1155 downstream of WWTPs. If the antimicrobial is not completely removed during 1156 treatment, exposures of humans to antim icrobials may also be associated with 1157 antimicrobials discharged to wastewater that enters WWTPs and subsequently 1158 enters surface water via WWTP effluents. Furthermore, there may also be the 1159 potential for terrestrial organisms and hum ans to be exposed to antimicrobial 1160 pesticides if the antimicrobial that is discharged to wastewater partitions to 1161 biosolids. 1162 Since the processing or end-use of an antimicrobial pesticide in an indoor 1163 setting does not preclude the potential for its release to ambi ent environmental 1164 media, particularly under circumstances in which there is potential for discharges 1165 of antimicrobial pesticides to wastewater , EPA believes that the designation of an 1166 antimicrobial use patterns as “indoor” is mi sleading. Based on the conclusion that 1167 processing or end-use of an antimicrobial pesticide in an indoor setting does not 1168 preclude its release to the ambient environment, EPA believes that a down-the1169 drain analysis is needed for all use patte rns with the exception of the aquatic 1170 areas use pattern. 1171 The commenter’s suggested use patterns are also inconsistent with EPA’s 1172 reevaluation of the data required for w ood preservatives. In response to 1173 comments, the Agency determined that a ll treated wood needs to be considered 1174 as having the potential to come into cont act with surface water. Therefore, for 1175 wood preservatives, EPA has changed seve ral data requirements in both the 1176 environmental fate table and the non-target organisms table from “CR” to “R.” 1177*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 52 of 234 However, under the comment er’s six suggested use pa tterns, wood preservatives 1178 would be considered to be the same as ma terial preservatives: The commenter 1179 did not differentiate the data needed betwe en the two use patterns. EPA believes 1180 that the data needed for a wood preservative is distinctly diffe rent from that 1181 needed for a materials preservative. Wood preservatives have a high potential for 1182 environmental exposure, as evidenced by both environmental fate and nontarget 1183 organisms data requirements th at are “R.” Material preservatives have a lower 1184 potential for environmental exposure and c onsequently are “CR.” Thus, the data 1185 requirements codified today acknowledge the differences in the data needed by 1186 having two distinctly different use patte rns: wood preservatives and material 1187 preservatives. 1188 Given the inclusion of the term “indoo r” as part of the title of three of the 1189 suggested use patterns, and the combining of wood preservatives and materials 1190 preservatives into a single use pattern, EPA believes that the six general use 1191 patterns suggested by the commenter (see above) would not adequately serve 1192 EPA’s or the public’s needs. Additionally, the 1997 review by the FIFRA Scientific 1193 Advisory Panel (SAP) of EPA’s 12 antimic robial use patterns indicated the SAP’s 1194 agreement that the Agency’ s proposed designation of 12 use patterns was a 1195 reasonable approach to organizing data requirem ents, and was, in fact, similar to 1196 the approaches used by Canada’s Pe st Management Regulatory Agency 1197 (PMRA), and the California EPA. Therefore, EPA is codifying the 12 use patterns 1198 that were proposed. 1199 B. Wood Preservative Use Pattern 1200*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 53 of 234 1. Comment. Several commenters questioned how wood preservatives 1201 were treated in the proposed rule. O ne commenter thought that all wood 1202 preservatives should be considered as having contact with water. Another 1203 commenter argued that the industrial, comm ercial and do-it-yourse lf uses of wood 1204 preservatives are different and should be assessed differently. 1205
2. EPA’s Response. Wood preservatives are pesticides for incorporation 1206 into wood products to control wood degradation problems due to fungal rot or 1207 decay, sapstain, molds, or wood-destroying insects. 1208 As explained in the proposed rule, (73 FR 59405) EPA’s current practice of 1209 determining the data required for a w ood preservative product is dependent upon 1210 where the product is intended to be used (l and-only versus l and and aquatic). 1211 Under this approach, fewer environmental fa te and ecological effects studies are 1212 required for products that limit their use pa tterns to land-only uses. This approach 1213 also assumes that diversion does not occu r and that wood that is treated for land1214 only uses does not end up in the water and vice versa. EPA specifically 1215 requested comments on the regulation of wood pres ervative products, and 1216 indicated that based on the comments re ceived could determine to continue with 1217 the current practice of considering land- only applications, or change to a land and 1218 aquatic usage. Based on comments indicati ng that the data requi red to register a 1219 wood preservative should not different iate between land only and aquatic only 1220 applications of treated wood, EPA has re-evaluated this approach. As discussed 1221 in the proposed rule, it is difficult to a ssure that diversion does not occur. EPA 1222 considered three possibilities: 1223*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 54 of 234  Assume all treated wood could have the potential to come into contact 1224 with surface water. 1225

 Use an approach similar to that advocated by the American Wood 1226 Protection Association (AWPA) a pproach which differentiates between 1227 marine/freshwater and ground contac t use/above ground contact use. 1228

 Maintain status-quo. 1229 Wood preservatives used to protect wood st ructures placed directly in or over 1230 water (e.g., marine pilings, docks) will leach active ingredient into the water, 1231 resulting in potential exposur e of aquatic organisms. Wo od preservatives used in 1232 the terrestrial environment for uses su ch as fences, siding, and decks will leach 1233 active ingredient into soil where it may be transport ed into the aquatic 1234 environment and expose aquatic organisms. 1235 The Emission Scenario Document (ESD ) for Wood Preservatives prepared 1236 by the Organization for Economic Co- operation and Development (OECD) as part 1237 of its Series on Emissions Scenario Documents provides guidance on how to 1238 estimate emissions of chemical substances in wood preservative products to air, 1239 water, and soil as a result both of produc t application and stor age of treated wood 1240 prior to shipment and treated wood-in-s ervice. This OECD ESD documents the 1241 occurrence of pathways of release of chemical substances during wood 1242 preservative application to facility drains that subsequently convey wastewater to 1243 WWTPs; entry of chemical substances to adjacent surface water bodies by way of 1244 run-off water from unpaved storage of wood preservative-treated products 1245 following a rain event; and leaching of chem ical substances from in-service uses 1246*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 55 of 234 of treated exterior wood out of ground (i.e., fences, noise barriers), wood in1247 ground (transmission poles, fence posts), a nd wood in direct contact with fresh 1248 and sea water (poles and planks/decking of jetties and wharfs). Additional 1249 information on indirect releases to surface water of antimicrobial pesticides used 1250 as wood preservatives can be found in response to comment 134.1 in the 1251 Response to Comments Document in the docket at http://www.regulations.gov

. 1252 Given the number of pathways identifi ed, that result in potential exposure 1253 from treated wood, the Agency dete rmined that all treated wood should be 1254 considered as having the potential to come into contact with surface water. All 1255 wood preservative risk assessments will no w be performed considering that the 1256 treated wood could end-up either on the l and or in the aquatic environment. As 1257 previously discussed, there are mult iple pathways for wood preservative 1258 degradates and/or leachates to reach surfac e water. The AWPA approach would 1259 have continued the practice of determi ning the data requirements based on the 1260 intended use site of the treated product. 1261 Given this decision, that all treated wood could have the potential to come 1262 into contact with surface water, the w ood preservative columns of the final 1263 Environmental Fate and the Nontarget Organisms Tables were revised. 1264 For the final Environmental Fate Tabl e, for the wood preservatives column, 1265 the data requirements for anaerobic soil metabolism, aerobic aquatic metabolism, 1266 and anaerobic aquatic metabolism were c hanged from “CR” to “R.” Because 1267 treated wood products have outdoor usages, the Agency believes that these 1268 products have the potential to come into contact with surface water as well as 1269*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 56 of 234 soils which can become flooded or wate rlogged and then be released to surface 1270
water. 1271 For the final Nontarget Organism T able, for the wood preservatives 1272 column, the data requirements for chronic to xicity testing with fish (fish early-life 1273 stage) and aquatic invertebrate (aquatic invertebrate life-cycle) are being changed 1274 from “CR” to “R” to prov ide chronic data when chronic exposure is expected. 1275 The Agency agrees that the industrial, commercial and do-it-yourself uses 1276 of wood preservatives are different in terms of human exposur e. Industrial wood 1277 preservative uses are assessed for those workers involved in the actual treatment 1278 of the wood with the preservative. Th is includes operations at a pressure 1279 treatment facility where workers add the preservative to treatment cylinders, 1280 remove treated wood charges from the cy linders, check the treated wood to verify 1281 retention rates, and move the freshl y treated wood around the facility (from 1282 cylinder to drip pad to storage to sh ipping). Industrial sapstain wood 1283 preservatives are also assessed at the tr eatment facility for t he application of the 1284 pesticide. Worker tasks fo r the non-pressure treatm ent (non-PT) are slightly 1285 different than those at pressure treatment (PT) facilities. Separate exposure 1286 measurements unique to each type of treat ment (PT vs non-PT) are used in the 1287
assessments. 1288 Exposures to commercial and do-it-y ourself uses of treated wood are 1289 assessed for those installing the treated wood and for those exposed to the 1290 treated structures (e.g., play sets and decks). 1291 VII. Discussion of Key Comments on General and Administrative Issues 1292*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 57 of 234 A. Scientific Advisory Panel (SAP) Waivers 1293 1. Comment. A commenter noted that in the preamble to proposed part 1294 158, subpart W, EPA cites multiple SAP repo rts that did not specifically mention 1295 antimicrobial pesticides. Therefore, t he commenter believes these SAP reviews 1296 were insufficient. Another commenter noted that it has been 9 years since the last 1297 SAP review and that EPA should reques t another SAP review prior to 1298 implementation of proposed part 158, s ubpart W. Still another commenter 1299 believes that EPA’s request that the SAP waive its review of proposed part 158, 1300 subpart W based on the SAP’s 1997 review was improper, and that the SAP 1301 cannot waive its statutory review obligation. 1302 2. EPA’s Response. EPA disagrees with the comments. On June 3, 1997, 1303 EPA presented an early version of the part 158, subpart W proposal in an open 1304 meeting to the SAP. At t hat time, the SAP provided ex tensive comments in five 1305 areas: Toxicology, residue chemistry, ecol ogical effects and environmental fate, 1306 human exposure, and efficacy. Since then, the SAP has considered many specific 1307 studies and scientific issues included in proposed part 158, subpart W as part of 1308 their reviews of guidelines and of data r equirements for conventional agricultural 1309 pesticides (see references 30, 31, 32, 33, and 34 to the proposed rule). In 1997, 1310 the SAP also noted its concern about the possible effects of antimicrobials on 1311 WWTPs. Partially in response to the SAP comments, EPA proposed a tiered set 1312 of environmental fate data requirement s that will allow the Agency to better 1313 characterize potential incidences of antimicr obials in surface waters, as a result of 1314 down-the-drain uses of antimicrobials. 1315*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 58 of 234 When the Agency prepared to propos e 40 CFR part 158, subpart W, EPA 1316 requested that the SAP waive its review of the about-to-be-proposed part 158, 1317 subpart W because there were no new scientific issues. The SAP waived its 1318 review of the about-to-be proposed par t 158, subpart W on February 19, 2008. 1319 The Agency continues to believe that t here are no new scientific issues that 1320 warrant additional review by the SAP. EPA’s request for an SAP waiver for the 1321 final antimicrobial data requirements rule is discussed in Unit XXIV. FIFRA 1322 section 25 requires EPA to give the SAP at least 60 days to review proposed 1323 regulations and 30 days to review final regulations. However, the SAP can 1324 determine to waive its review during statutory time periods. 1325 C. Risk Assessments for Wood Preservatives. 1326 1. Comment . A commenter noted that Canada’s PMRA and USEPA 1327 conduct risk assessment for wood preservatives differently. EPA’s risk 1328 assessment is based on the treated wood wh en used at the final use site, while 1329 the PMRA’s risk assessment is based at t he site where the wood is treated. The 1330 PMRA also does not distinguish between terrestrial-only or aquatic-only use for 1331 anti-sapstains and heavy-dut y wood preservatives. 1332 2. EPA’s Response . The Agency acknowledges differences between 1333 its risk assessment of wood preservati ves and that of Canada’s PMRA. As 1334 previously discussed in Unit VI.A, EPA has re-evaluated its approach for 1335 determining the data required for a wood pr eservative product. As part of the re1336 evaluation, EPA considered the human and ecological risks based on exposure 1337 pathways identified in OECD’s ESD for Wood Preservatives. This ESD identifies 1338*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 59 of 234 potential human and ecological exposure s from both treatm ent of wood at 1339 processing facilities and in-service uses on land and in water. The Agency 1340 determined that all treated wood should be considered as having the potential to 1341 come into contact with surface water. This determination reflects EPA’s concern 1342 about the potential for the indirect re lease to surface waters of wood 1343 preservatives. As a result, EPA is changing its approach to requiring 1344 environmental and ecological effects studi es for wood preservatives. All wood 1345 preservative risk assessments will now be pe rformed considering that the treated 1346 wood could end-up either on the land or in the aquatic environment, thus 1347 increasing harmonization between PM RA and EPA with regard to wood 1348 preservatives. 1349 D. Clarity on How and When CR Data is Required 1350 1. Comment. A commenter asked EPA to s pecify criteria to determine 1351 whether a data requirement is “R” (Required) or “CR” (Conditi onally Required). 1352 According to the commenter, the discussion of “R” and “CR” suggests that a data 1353 requirement labeled “CR” may not be requi red to be addressed by the applicant. 1354 A second commenter stated t hat it is unclear how and when conditionally required 1355 data are triggered. Another commenter asserted that data requirements should 1356 be waived only under extraordinary circum stances, and that the use of waivers 1357 can effectively preclude appropriate regul ation of the pestic ide under FIFRA. 1358 2. EPA’s Response . In its proposed data requirement tables, EPA 1359 specified whether a data requirement is “Required”, “Conditiona lly Required”, or 1360 “Not Required” based on how likely the study is needed to complete an 1361*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 60 of 234 assessment of an antimicrobial pesticide. As a rule of thumb, a “required” study is 1362 likely to be needed 50 percent of the time or more and a “conditionally required” 1363 study is likely to be needed less than 50 per cent of the time. Typically, a 1364 “conditionally required” study is triggered based on the results of a study that has 1365 already been conducted. Triggers in the te st notes indicate the circumstances 1366 under which the Agency has learned through experience that the information is 1367 needed. In many instances, the app licant would be able to make the 1368 determination that the tr igger has been met and should include the data in their 1369 original submission. In other cases, EPA will make the determination based on its 1370 review of submitted data and would then request additional data from the 1371 applicant. EPA encourages applicants to co nsult with the Agency to determine 1372 the actual need for the data. 1373 All data requirements must be addre ssed by the applicant by either 1374 conducting the study or submitting in formation that could fulfill the data 1375 requirement, such as citing open literature or other data sources, or by requesting 1376 and receiving a data waiver. EPA grants dat a waiver requests only on a case-by1377 case basis and only when the available ev idence indicates a particular study is 1378 not needed or that there are particular reasons for not conducting the study. For 1379 example, if the physical/ chemical properties of t he chemical did not lend 1380 themselves to the testing procedure, su ch as performing an inhalation study with 1381 a chemical that is a solid and has an extr emely low vapor pressure, then a waiver 1382 might be granted. EPA also grants waiver s in exceptional circumstances, for 1383*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 61 of 234 instance, if a test substance is so co rrosive that animal studies would cause 1384 undue pain and suffering. 1385 VIII. Discussion of Key Comments on Product Chemistry 1386 The following represent the signifi cant comments received on the need for 1387 and evaluation of product chemistry studies as proposed by EPA. 1388 A. Application of Subpart D Product Chemistry Data Requirements to 1389 Antimicrobials. 1390 1. Comment . A commenter requested that EPA provide adequate 1391 justification for applying the existing pr oduct chemistry data requirements for 1392 conventional pesticides to antimicrobial s without consideration of the highly 1393 dissimilar chemistries and inapplicabili ty of many of the requirements. 1394 2. EPA’s Response . It has been EPA’s longstanding practice to require 1395 product chemistry data. Product chemistry data are required to identify the 1396 chemicals used to manufacture a pr oduct and to understand the physical and 1397 chemical properties of t he ingredient or product. Su ch information is generally 1398 independent of the intended use pattern. Product chem istry data are used during 1399 label development to identify information to be included on the label, such as the 1400 flammability statement, and directions for disposal of the product. Hence, despite 1401 any differences between conventional and antimicrobial pesticides, the Agency 1402 believes it is appropriate to apply the sa me product chemistry data requirements 1403 to antimicrobials as required for conv entional pesticides. The guidelines for 1404 conducting product chemistry studies offer fl exibility to account for differences 1405 between chemical classes. 1406*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 62 of 234 B. Lack of Adequate Opportunity for Review of Product Chemistry Data 1407 Requirements 1408 1. Comment . One commenter asserted that registrants of antimicrobial 1409 pesticides were not given the opportunity to review and comment on conventional 1410 pesticide data requirements that are now being proposed for antimicrobial 1411 pesticides. 1412 2. EPA’s Response. .In the preamble to pro posed part 158, subpart W, 1413 EPA proposed to apply the product chemistr y data requirements for conventionals 1414 in 40 CFR part 158 subpart D to antimicrobi al pesticides. Therefore, during the 1415 public comment period for the proposed par t 158, subpart W, from October 8, 1416 2008, to April 6, 2009, any interested party could have commented on the product 1417 chemistry data requirements in subpart D (which have been in place since 1418 October 2007) and their potential appl icability to antimicrobials. 1419 IX. Discussion of Key Comments on Product Performance Data 1420 Requirements 1421 The following represent the signifi cant comments received on the need for 1422 and evaluation of product performance st udies as proposed by EPA. Changes 1423 from the proposed rule to the final rule are also described. 1424 A. Product Performance Guidelines 1425 1. Comment. Several commenters shared their belief that EPA was 1426 seeking to avoid comment on the produc t performance data requirements in the 1427 proposed rule by stating that the Agen cy” is not proposing to revise product 1428 performance data requirements” at this time. Another commenter asked how the 1429*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 63 of 234 product performance section of the proposed rule could be finalized without the 1430 810 guidelines? 1431 2. EPA’s Response . The proposed product performance data 1432 requirements table contained the older 91 series guidelines. As stated in the 1433 proposed rule the requirements being propos ed were “nearly identical” to the 1434 existing data requirements in § 158. 400 and 161.640, and the table was 1435 “transferred essentially unchanged” ( 73 FR 59391). Since the 2008 proposed 1436 rule, EPA published the draft 810 guidelines for comment. Four of the 810 series 1437 guidelines (810.2000, 810.2100, 810.2200, and 810.23 00 for sterilants, 1438 disinfectants and sanitizers) were published in the Federal Register for public 1439 comment on January 27, 2010 (75 FR 4308) . These guidelines represent the 1440 Agency’s current recommendations for cond ucting product performance studies to 1441 support antimicrobial pesticide label claims. That Notice of Availability announced 1442 that the 810 guidelines series woul d be incorporated into the final data 1443 requirements regulation: As announced, in th is final rule EPA is replacing the 91 1444 series designations proposed in the part 158, subpart W product performance 1445 table with the appropriate 810 Series Guideline numbers and names. Thus, 1446 commenters had an opportunity to comment on the inclusion of the 810 series in 1447 the final Product Performance Data Require ments table. Three additional product 1448 performance guidelines (810.2400, 810.2500, and 810.2600) should be published 1449 for comment in a timeframe similar to t hat of publication of the final rule for 1450 Antimicrobial Data Requirements. S ee Unit XVIII for a di scussion on guidelines. 1451 B. Emerging Pathogens 1452*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 64 of 234 1. Comment . A commenter asked why there is no formal regulatory 1453 practice for registering products to address public health emergencies or 1454 emerging pathogens promptly and effectively? 1455 2. EPA’s Response . EPA does not believe that the promulgation of a rule 1456 dealing with data requirement s is the appropriate pl ace to address emerging 1457 pathogens. A major consideration in the Agency's process for addressing public 1458 health emergencies and emerging pathogens is to work closely with the Centers 1459 for Disease Control and Prevention (CDC), Department of Agriculture (USDA), 1460 and FDA, as appropriate, to provide a ti mely and accurate response to these 1461 situations. Under FIFRA sect ion 18, the Agency also has authority to grant certain 1462 exemptions from the prov isions of FIFRA and also to approve the use of 1463 unregistered pesticides when emergency condi tions exist. Additionally, in April 1464 2008, the Agency implemented a disinfec tion hierarchy policy for addressing 1465 emerging viral pathogens. Information on this policy is available on the EPA 1466 website at http://www.epa.gov/oppad001/disinfection_hier.htm

. EPA believes that 1467 emerging pathogens require flexibility and speed in disseminating information and 1468 seeks to address such situations in a prompt and effe ctive manner. 1469 C. Definitions of Sanitizer and Disinfectant 1470 1. Comment . Several commenters claimed t hat the proposed definitions 1471 do not reflect the work done by the regul ated community in cooperation with EPA 1472 since 1999. In particular, these co mmenters did not agr ee with the proposed 1473 definitions of saniti zer and disinfectant. 1474 2. EPA’s Response . Since the publication of the proposed rule, the 1475*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 65 of 234 definitions, including those for sanitize r and disinfectant, were published in the 1476 Federal Register for public comment on January 27, 2010, as part of requesting 1477 comment on draft guideline 810.2000. A fter further review of the comments 1478 submitted on the proposed definition for disi nfectant and sanitizer, the Agency has 1479 revised the definitions that had been pr oposed for both part 158, subpart W and 1480 the 810 Guidelines. EPA believe s that the definitions being codified today reflect 1481 the input received from the regulated community in multiple submissions. The 1482 definitions for sanitizer and disinfectant will be the same in both part 158, subpart 1483 W and in the 810 Guidelines. 1484 The definition for disinfectant is be ing revised from, “Disinfectant means a 1485 substance, or mixture of substances that destroys or eliminates a specific species 1486 of infectious or public health microorganism , but not necessarily bacterial spores, 1487 in the inanimate environment” to read, “Disinfectant means a substance, or 1488 mixture of substances, that destroys or i rreversibly inactivates bacteria, fungi and 1489 viruses, but not necessarily bacterial s pores, in the inanimate environment.” 1490 The definition for sanitizer is being revised from, “Sanitizer means a substance, or 1491 mixture of substances that reduces the bacterial population in the inanimate environment by 1492 significant numbers, but does not destroy or eliminate all bacteria or other microorganisms” to 1493 read, “Sanitizer means a substance, or mixture of substances that reduces the bacterial population 1494 in the inanimate environment by significant numbers, (e.g., 3 log 10 reduction) or more, but does 1495 not destroy or eliminate all bacteria. Sanitizer s meeting Public Health Ordinances are generally 1496 used on food contact surfaces and are termed sanitizing rinses.” 1497 The definitions for fungicide, steril ant, tuberculocide and virucide are being 1498 revised to include the following phrase: “or mixture of substances.” Inclusion of 1499*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 66 of 234 this phrase in all of the definitions in § 158.2203 for types of products that bear 1500 public health claims (excepting microbiolog ical water purifier) means consistency 1501 in the definitions and an acknowledgement that the destroying, reducing, or 1502 inactivating may be accomplis hed via more than a single substance. Also, this 1503 makes these definitions similar to the FI FRA section 2(u) definition of pesticide 1504 which also contains the phrase “or mixture of substances.” 1505 Additionally, the definition for virucide is being revised to include the word 1506 irreversibly, as follows: “Virucide means a substance, or mixture of substances, 1507 that destroys or irreversibly inactivates viruses in the inanimate environment,” thus 1508 reading similar to the definition for tubercu locide. Additionally, the definition for 1509 sterilant will be revised to remove the sec ond sentence of the proposed definition: 1510 “For purposes of this subpart, ‘sporicide’ and ’sterilant’ ar e synonymous.” EPA no 1511 longer requires that products that make sporicidal claims also make sterilant 1512 claims. 1513 D. Nonpublic Health Data and Claims 1514 1. Comment . A commenter asked that t he issue of when to generate 1515 efficacy data for nonpublic health products be discussed, since registrants are 1516 required to develop data to substantiate label claims. 1517 2. EPA’s Response . The Agency believes this issue has been addressed 1518 in § 158.2220 "Product Performance," whic h clearly states, "Each applicant must 1519 ensure through testing that his product is efficacious when used in accordance 1520 with label directions and commonly accept ed pest control practices.” However, to 1521*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 67 of 234 clarify the issue further, the Agency is adding a definition for nonpublic health 1522 claims that will appear as 40 CFR 158.2204(b): 1523 Nonpublic health claim . An antimicrobial pesticide is 1524 considered to make a nonpub lic health claim if the 1525 pesticide product bears a claim to control 1526 microorganisms of economic or aesthetic significance, 1527 where the presence of t he microorganism would not 1528 normally lead to infection or disease in humans. 1529 Examples of nonpublic health claims include, but are 1530 not limited to, algaecides, s limicides, preservatives 1531 and products for which a pesticidal claim with respect 1532 to odor sources is made. 1533 1534 Additionally, EPA is revising 40 CFR 158.2220(c)(3) to read: 1535 (3) Product performance data for each product that 1536 bears a nonpublic health claim. Each product that 1537 bears a nonpublic health clai m, as described in 1538 §158.2204(b), must be supported by product 1539 performance data. Each registrant must ensure 1540 through testing that his product is efficacious when 1541 used in accordance with label directions and 1542 commonly accepted practices. The Agency reserves 1543 the right to require, on a case-by-case basis, 1544 submission of product performance data for any 1545 pesticide product registered or proposed for 1546 registration or amendment. 1547 1548 Also, EPA has posted on the Antimicrobials Division website the parts of the 91 1549 Guideline series that apply to testi ng of nonpublic health products. Although 1550 these guidelines are from 1982, they ar e still relied on to develop data to support 1551 nonpublic health label claims. EPA acknowle dges that some of the references in 1552 the 1982 guidelines are to the older 91 seri es, which is being replaced by the 810 1553 series. To assist readers, EPA has also posted a cross-walk table so readers can 1554 locate the applicable section of the 810 Guidelines. 1555 X. Discussion of Key Comments on Toxicology Data Requirements 1556*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 68 of 234 The following represent the signifi cant comments received on the need for 1557 and evaluation of toxicology studies as proposed by EPA. Changes from the 1558 proposed rule to the final rule are also described. 1559 A. TTC Approach 1560 1. Comment . There should be a threshold of toxicological concern (TTC) 1561 type of approach for antimicrobials. 1562 2. EPA’s Response. OPP’s Antimicrobials Division is aware of the TTC 1563 concept, and in conjunction with ILSI, is currently pursuing the development of an 1564 application of the TTC concept to evaluate antimicrobial pes ticides. At this time, 1565 EPA anticipates a timeframe of 2 to 3 y ears for development. Once a TTC-based 1566 approach has been developed and piloted, then EPA would consider when/if the 1567 approach should be included in part 158, subpart W. 1568 B. Test Note to Neurotoxicity Studies 1569 1. Comment . A commenter stated that proposed test note 6 to the 1570 proposed toxicology table in § 158.2230 tr iggering the neurotoxicity studies is 1571 contradictory and unclear. The comm enter asked how the absence of a 1572 neurotoxicity screen in the 90-day oral r odent study would impact proposed test 1573 note 6? 1574 2. EPA’s Response. Proposed test note 6 s pecifies that if the 1575 neurotoxicity screen that occurs in the 90- day oral rodent study or any other data 1576 demonstrate neurotoxic effe cts, then both t he acute neurotoxicity study and the 1577 90-day neurotoxicity study are triggered. For certain use patterns with the 1578 potential for larger exposures (most notabl y food exposures), all three of these 1579*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 69 of 234 studies are initially required. Accordi ng to proposed test note 8 to the proposed 1580 toxicology table in § 158. 2230, the applicant may combine the 90-day oral toxicity 1581 study and the 90-day neurotoxicity study by adding a separate group of test 1582 animals. 1583 However, for some use patterns, the 90-day oral study is required, and the 1584 other two studies are conditionally requi red, being triggered by proposed test note 1585 6. EPA acknowledges that when only t he 90-day oral study is required, an 1586 applicant is at a disadvantage in terms of any chance for combining the 90-day 1587 neurotoxicity study with the oral study: Once the 90-day or al study with its 1588 neurotoxicity screen has been performed, and neurotoxic effects are identified, 1589 then it is not possible to add a separate group of test animals to the already 1590 conducted study. 1591 As a point of clarification, EPA is adding a new test note to the final 1592 Toxicology Table in § 158.2230(g) to clarif y that the neurotoxicity screen that is 1593 part of the 90-day oral study is not equivalent to a 90-day neurotoxicity study. If 1594 the 90-day oral toxicity study does not have a neurotoxicity scr een, then the acute 1595 neurotoxicity study in the rat would be requir ed. The new test note also includes: 1596 “if the 90-day oral rodent study does not include a neurotoxicity screen, then the 1597 acute neurotoxicity study will be required.” As part of r enumbering, this new test 1598 note is now test note 11 to the Toxicolo gy Table in the final rule, § 158.2230(g). 1599 C. End-Product Use-Dilution Toxicity Testing 1600 1. Comment. Several commenters stated their belief that acute end 1601 product use-dilution toxicity testing should be optional and requested greater 1602*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 70 of 234 clarification on when to test a dilut ed product. The commenters asked whether 1603 extrapolation from t he active ingredient or as-sold acute toxicity testing is 1604 acceptable? Another commenter clai med that requiring end-product six-pack 1605 testing of one or more dilutions is duplicative. 1606 2. EPA’s Response. Proposed test note 2 to the proposed toxicology table 1607 in § 158.2230, specifies how to conduct acut e toxicity testing for end-use products 1608 (EP). EP testing is conducted on t he product as formulated for sale and 1609 distribution. From the EP acute toxicity studies, EPA derives toxicity categories 1610 which are then used to determine the pr ecautionary labeling statements on the 1611 product. However, it is common for some products to be diluted before being 1612 used. The use-dilution testing is in additi on to the as-formulated-for-sale testing 1613 since there are exposures to both. Acut e toxicity testing on the product that has 1614 been diluted-for-use supplies the info rmation needed to derive precautionary 1615 statements for the user of the product. EPA is revi sing proposed test note 2 to 1616 make this clearer. 1617 D. The Phrasing “limited portion of the human lifespan” 1618 1. Comment . Several commenters asked EPA to identify the criteria to 1619 determine “repeated human exposure over a limited portion of the human life 1620 span.” They asked EPA to specifica lly describe what the phrase “human 1621 exposure is not purposeful” means? 1622 2. EPA’s Response . Proposed test note 11 to the proposed toxicology 1623 table in § 158.2230, specifies the triggers that would require the performance of a 1624 90-day oral study in the non-rodent. EPA has re-evaluated this test note and 1625*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 71 of 234 decided to remove test note 11 from proposed part 158, subpart W. Proposed 1626 test note 11(i) contained the phrase “repeated human exposure over a limited 1627 portion of the human life span.” EPA agree s that this phrase is not useful. 1628 Proposed test note 11(ii) contai ned a trigger for any indirect food use that would 1629 have been considered to be a “low exposure.” Given the restructuring of the final 1630 Toxicity Data Requirements Table, i.e. , the shift away from using high and low 1631 exposure as the table headers to a f ood/nonfood approach, test notes 11(i) and 1632 11(ii) are no longer needed. In the final To xicity Table in § 158.2230(g), the data 1633 required for an indirect food-use is spec ified directly (in the table header) and a 1634 trigger is not needed. As discussed in Unit X.B, proposed test note 11 is replaced 1635 by a different test note as part of re- numbering. 1636 Proposed test note 12 to the proposed toxicology table in § 158.2230, 1637 specifies three triggers that would requi re the performance of a 21/28-day dermal 1638 study. EPA has also re-evaluated te st note 12 and agrees that the phrases 1639 “repeated human exposure over a limited portion of the human life span” and 1640 “human exposure is not purposeful” are not useful. EPA has decided to remove 1641 the first two of the tri ggers. Therefore, the 21/28 day dermal study is now 1642 triggered if the intende d use of the antimicrobial pesticide product is expected to 1643 result in dermal human exposure to the product, data from a subchronic 90-day 1644 dermal toxicity study are not available, and the 90-day dermal toxicity study has 1645 not been triggered (the th ird proposed trigger). 1646 E. Mouse Carcinogenicity Study 1647*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 72 of 234 1. Comment. According to severa l commenters, the mouse 1648 carcinogenicity study does not provide us eful information, and is, in fact, not 1649 suited for determining/extrapolating human carcinogenicity. They contended that 1650 EPA should no longer require the mouse carcinogenicity study. This would also 1651 mean that there is no need for the mouse range-finding study. 1652 2. EPA’s Response . The issue regarding the usefulness of the mouse for 1653 carcinogenicity testing is one that is currently under debate by the OPP. 1654 Currently, carcinogenicity te sting, whether for convent ional under § 158.500 or for 1655 antimicrobials under part 158, subpart W requires testing in two rodent species. 1656 However, OPP is currently conducti ng a comprehensive analysis of its rodent 1657 chronic bioassay database to document the utility of the mouse bioassay for both 1658 cancer risk assessment and Reference Do se (RfD) derivation for non-cancer 1659 endpoints. When this analysis is comp leted, a recommendation will be made 1660 regarding the testing needed for cancer hazar d identification. OPP anticipates 1661 completing this analysis during 2012. On ce OPP’s internal review process is 1662 complete, then it is likely that EPA would solicit review and comment by the 1663 FIFRA SAP. If at a later date, th e determination is made to alter the 1664 carcinogenicity data requirements, then appropriate changes would be proposed 1665 to be made to data requirements and regul ations pertaining to conventionals, 1666 biochemicals and microbials, and antim icrobials through rulemaking. 1667 F. Ames Assay 1668 1. Comment . A commenter argued that the Ames assay should not be 1669 required, because it is inappropriate fo r antimicrobials that kill bacteria. 1670*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 73 of 234 2. EPA’s Response . It is recognized that the Ames assay may not be 1671 useful for assessment of mu tagenic potential of antimicr obial pesticides, as this 1672 test uses strains of bacteria as the pr imary test material, and antimicrobials are 1673 designed to kill, among other things, bac teria. So, the bacteria may be killed 1674 before mutagenic effects are demonstrated . However, for so me antimicrobial 1675 pesticides, the Ames assay has already been conducted and if the Ames assay 1676 was conducted at levels that do not cause to xicity to the bacterial strains tested, 1677 then the study may be acceptable to fulfill the reverse mutation asay requirement. 1678 However, if an Ames assay has not yet been conducted for a particular 1679 antimicrobial, then, the Ames assay should not be conducted. In this final rule, 1680 test note 32 for the revers e mutation assay requirement to the final Toxicology 1681 Table in § 158.2230(g), is revised to allo w reliance on previously-conducted Ames 1682 tests when the bacteria strain was not kill ed, but to state a preference for assays 1683 such as an in vitro mammalian cell assay, (e.g., the mouse lymphoma TK +/- 1684 assay). 1685 G. Dermal Absorption Studies 1686 1. Comment . A commenter argued that EPA should accept in vitro skin 1687 penetration data. According to the commenter, accepting such data would 1688 harmonize with requirements in the Eur opean Union (EU) and elsewhere. The 1689 commenter pointed to well-established OECD guidelines for these studies. The 1690 commenter also asserted that proposed te st note 37 to the proposed toxicology 1691 table in § 158.2230, addressing the require ment for a dermal absorption study, 1692 should not apply to corrosi ve/irritant products. 1693*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 74 of 234 2. EPA’s Response . The Agency has, on a case-by-case basis, used in 1694 vitro dermal absorption studies to determi ne the magnitude of dermal absorption 1695 of pesticide chemicals. However, the Agency has not adopted an official policy of 1696 using only in vitro data to support these decisions . The OECD guideline 428, while 1697 describing an in vitro method for dermal absorption, does not rule out the use of in 1698 vivo data along with in vitro data to determine dermal absor ption. Further, the test 1699 guideline notes that formal validation studies of the in vitro method have not been 1700 performed. 1701 The Agency is working on developing a more formal policy that would use 1702 both in vivo and in vitro dermal penetration data in a weight-of-evidence (WOE) 1703 determination in appropriate cases. The Agency would always consider QSAR or 1704 other models, submitted in support of t he determination of dermal absorption. 1705 The decision to accept such information is the Agency’s, based on its review and 1706 evaluation of the submission. 1707 Proposed test note 37 to the proposed toxicology table in § 158.2230, 1708 specifies that the trigger for requiring a dermal penetration study are the results 1709 from a risk assessment “assuming that dermal absorption is equal to oral 1710 absorption.” This means that EPA assu mes 100 percent dermal absorption. If a 1711 subchronic dermal study and/or dermal absor ption data are not available, then a 1712 risk assessment could be conducted using t he default assumption of equivalent 1713 absorption by the dermal and oral routes of exposure. If unacceptable risks are 1714 found, then either the s ubchronic dermal study or a dermal absorption study 1715 would be required. EPA recognizes that the assumption of 100 percent dermal 1716*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 75 of 234 absorption is conservative; however, this assumption would only be used in the 1717 absence of an acceptable dermal subchronic study or dermal absorption data. In 1718 this final rule, test note 37 to the Toxico logy Table in § 158.2230(g), is revised to 1719 clarify this process. EPA also agrees that corrosive/irritant products should not be 1720 tested in dermal absorption studies. Therefor e, test note 3 to the Toxicology Table 1721 in § 158.2230(g), which specifies that testing is not needed for corrosive 1722 materials, is added as a trigger for not requiring the dermal absorption study. 1723 H. Tiering 1724 1. Comment. One commenter argued t hat EPA has not provided 1725 meaningful tiering for its toxicology r equirements for antimicrobials. Another 1726 commenter claimed that exposure alone is not an appropriate criterion to use for a 1727 tiered testing scheme, that both exposure and risk should be considered. A third 1728 commenter asserted that the high and low human exposure categories for toxicity 1729 are not appropriate and suggested that a tiered scheme such as that used for 1730 environmental fate data requirement s would be more appropriate. 1731 2. EPA’s Response. EPA disagrees with thes e comments. In its 1732 proposed rule EPA proposed a tiered testing scheme for toxicology testing that 1733 was based on the amount of exposure as defined by use patterns. Based on its 1734 experience in conducting risk assessment s, EPA understands which use patterns 1735 have exposures of higher duration and m agnitude, and therefore could have 1736 greater risks. Use patterns with higher exposures require more submission of 1737 data than use patterns with lower exposures. 1738 I. Guideline Numbers in CFR 1739*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 76 of 234 1. Comment. A commenter stated t hat the final rule should not specify a 1740 guideline number. In stead, the data requirement tables should describe the 1741 endpoint in question, and the informati on needed for EPA’s risk assessment. 1742 OPP could develop guidance that could be placed on the web. 1743 2. EPA’s Response . EPA agrees with this comment. The guideline 1744 number column could be removed from t he table. Instead, EPA could have an 1745 internet page that describes multiple met hods of fulfilling the data requirements. 1746 An internet table could be updated fast er to reflect newer techniques than 1747 rulemaking to revise regulation in the CFR. However, there is also value in having 1748 the guideline number in the CFR, which then shows t he available guidelines 1749 relevant to the particular study that should be considered in addressing the 1750 requirement. EPA has made no decision on whether or not to initiate a 1751 rulemaking to remove all the guideline numbers from the data requirement tables 1752 in 40 CFR part 158. The tables finalized in subpart W in this rule include guideline 1753 numbers. 1754 J. Animal Testing 1755 1. Comment. A commenter requested that E PA specifically state in its 1756 regulations that non-animal methods are acceptable for fulfilling a data 1757 requirement. The commenter argued t hat the Draize study (the acute eye 1758 irritation study) in rabbits should be eliminated. 1759 2. EPA’s Response . Non–animal test methods are continually being 1760 examined for use in fulfilling the toxicol ogy data requirements that are used to 1761 assess the hazard of pesticide chemical s. However, in order for non-animal 1762*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 77 of 234 approaches to be used for fulfilling to xicology data requirements, these 1763 approaches must first be scientif ically validated to ensure that they are as good as 1764 the existing test method for predicti ng hazard and also assessed to determine 1765 whether they meet the Agency’s “3 R” goals of reduce, refine, and replace the 1766 use of animals in testing. With respec t to antimicrobial pesticides, the Agency has 1767 started to explore such appr oaches. One example of this is the voluntary pilot 1768 program for eye irritation testing of antim icrobial pesticides using non–animal test 1769 methods, found at http://www.epa.gov/oppad001/ eye-irritation.pdf

. 1770 K. Derivation of 200 Parts per Billion Criterion 1771 1. Comment . A commenter asked whether the 200 parts per billion (ppb) 1772 level used as the dividing line betw een high and low human exposures is the 1773 concentration of a substance in an adult’s daily food consumption? 1774 2. EPA’s Response. The derivation of the 200 ppb level was previously 1775 established by FDA for indirect food use biocides, and is described in the 1776 proposed rule (73 FR 59394, October 8, 2008). (Also, see document 10 in the 1777 docket at http://www.regulation.gov .) As discussed in the proposed rule, the 200 1778 ppb is derived by dividing FDA’s cumulati ve exposure upper limit of 1000 ppb 1779 level by 5 to account for the fact that antim icrobial pesticides (e.g., biocides) are a 1780 class of pesticide that are generally toxi c by design. The 200 ppb level is the 1781 concentration of the antimicrobial residues in or on the food item. EPA is using 1782 200 ppb as a delineation consistent with the FDA’s toxicology recommendations 1783 for food contact substances. Therefore, those indirect food uses that have 1784 residues that are less than or equal to 200 ppb in or on the food item usually have 1785*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 78 of 234 fewer data requirements than those that have residues t hat are greater than 200 1786 ppb in or on the food item. For clarity, the following information concerning the 1787 200 ppb level and its derivation from FDA levels has been added to § 1788 158.2230(d): 1789 The 200 ppb level was orig inally used by the Food 1790 and Drug Administration with respect to the 1791 concentration of residues in or on food for tiering of 1792 data requirements for indirect food use biocides. The 1793 Agency has also adopted this same residue level for 1794 determining toxicology data requirements for indirect 1795 food uses of antimicrobial pesticides. The 200 ppb 1796 level is the concentration of antimicrobial residues in 1797 or on the food item. 1798 1799 L. Use of OECD Guidelines for EPA Registrations 1800 1. Comment . A commenter asked EPA to consider incorporating the 1801 following OECD guidelines into the new par t 158, subpart W to reduce the number 1802 of animals killed in LD 50 tests: OECD guidelines 436; Acute Inhalation Toxicity - 1803 Acute Toxic Class Method, and revised 223; Avian Acute Oral Toxicity Test, and 1804 Short Guidance on the Threshold A pproach for Acute Fish Toxicity. 1805 2. EPA’s Response . OPP does not have a policy for use of OECD 436 for 1806 acute inhalation toxicity. If a stud y conducted according to OECD 436 were 1807 submitted for the purpose of assessing acute inhalation toxicity, EPA would 1808 review and accept the results if the study were conducted in an acceptable 1809 manner and provided sufficient informati on to fulfill the data requirement. 1810 Similarly, if a study conducted acco rding to OECD 223 or the Threshold 1811 Approach, were submitted, then EPA would review the study and then make a 1812*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 79 of 234 determination on whether the study wa s conducted in an acceptable manner and 1813 provided sufficient information to fulfill the data requirement. 1814 M. Alternative Formats for Toxicology Data Requirements Table Suggested by 1815 Commenters 1816 1. Comment . In the comments submi tted to EPA, the commenters 1817 suggested two alternative toxicity data requirement approaches for EPA to 1818 consider. Alternative approach 1 was or ganized in paragraphs and alternative 1819 approach 2 was in a table format si milar to that proposed by EPA. 1820 2. EPA’s Response . The commenters provided two alternative 1821 approaches for toxicology data requirements for antimicrobial s. As stated by the 1822 commenter, alternative approach 1 was “int ended to provide clearer instructions 1823 to registrants,” attempted “to fully inco rporate the new science” of integrative 1824 approaches to testing, and included “a threshold concept for toxicological 1825 concerns.” (ACC Comment in the docket at http://www.regulations.gov ; document 1826 EPA-HQ-OPP-2008-0110-0088.6; Appendix E, entitled “C omments on Proposed 1827 Data Requirements for Toxicology” p. 24). The commenter did not provide to 1828 EPA the same or similar table-type of fo rmat used for part 158 data requirements. 1829 There were no test notes to define the tri ggers for moving from tier to tier. The 1830 commenter acknowledged that their suggested alternative approach 1 would 1831 require “expert scientific judgment” (p. 25), and discussed that in the proposed 1832 rule (59423) that EPA had indicated t he need for scientific position papers, and 1833 recommendations for internal and external review. EPA considers alternative 1834 approach 1 to be a dramatic departure fr om EPA’s proposal, and agrees with the 1835*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 80 of 234 commenter that certain scientific issues may not be ready for codification. EPA 1836 does not believe, at this time, that th is approach meets the needs of the Agency, 1837 or has any advantages over the t able format. EPA found the paragraph 1838 explanations unclear. As acknowledged by the commenter, the paragraph format 1839 would result in a more complex decision tree that would require a significantly 1840 greater amount of interpretation and cons ultation when compared to the existing 1841 table formats. There would be a si gnificant learning curve for both EPA and 1842 those members of the public that have become accustom ed to data requirement 1843 tables such as in part 158. Within this response, EPA has responded to 1844 alternative approach 1 in tota lity. EPA notes that the individual scientific issues 1845 raised within the paragraphs are addressed s eparately, as they were separated 1846 into the various disciplinary areas of the toxicology comments. 1847 EPA has also evaluated alternative appr oach 2. This alternative approach 1848 is in a table-type of form at with a strict split be tween food and nonfood uses. The 1849 test notes developed by the commenters are extrem ely detailed and contain 1850 information that EPA believes is more appropriate in guidance. However EPA has 1851 used the suggested test notes to revise its proposed testnotes as appropriate. 1852 For example, the commenters’ suggested test note 32 to the in vivo cytogenetics 1853 study is clearer than EPA’s proposed test no te 34. Therefore EPA is revising test 1854 note 34 to the final Toxicology T able in § 158.2230(g), accordingly 1855 As discussed previously, as a result of comments received, EPA is no 1856 longer using the terms “high human ex posure” and “low human exposure” as 1857 proposed for the antimicrobial toxicology da ta requirements table. Instead, in the 1858*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 81 of 234 final rule, EPA is now using a food/nonfood appr oach with some similarities to that 1859 of the toxicology data requirements table for conventional pesticides to distinguish 1860 the use patterns with higher exposure that n eed more toxicity data from those that 1861 need less. Accordingly, the table headers for the Toxicology Data Requirements 1862 Table in the final rule are: “Direct F ood Uses;” “Indirect Food Uses (>200 ppb);” 1863 “Indirect Food Uses ( ≤ 200 ppb);” “Swimmers, Aquatic Areas, Wood Preservatives, 1864 Metal Working Fluids;” and “A ll Other Nonfood Uses.” 1865 Unlike conventional pesticide chemical s, a strict food/nonf ood use “split” for 1866 delineating data requirements is not appropriate for antimicrobial chemicals. Such 1867 an approach does not fully address the uni que use patterns for antimicrobials, 1868 most specifically, those involving indire ct food uses. As a result of comments 1869 received, EPA decided to employ a modifi cation of the food/nonfood approach to 1870 delineate the specific data requirement needs for antimicrobial pesticides. 1871 The commenter has also asked that EPA include within subpart W a new § 1872 158.2235 which would be analogous to 40 CFR 158.510 for conventional 1873 chemicals (Tiered Testing Options for Nonfood Use Pesticides). EPA does not 1874 believe this is needed for antimicrobials. Once it has been determined that the 1875 use is nonfood, then certain of the nonf ood use scenarios require the submission 1876 of more data, and certain require the submi ssion of less data. As specified in the 1877 column headings for Nonfood Uses, swimming pools, aquatic areas, wood 1878 preservatives, and metal working fluids requi re a particular set of data. All other 1879 nonfood uses require less data. Thus, the ti ering is already built into the approach 1880 used for antimicrobials. 1881*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 82 of 234 XI. Discussion of Key Comments on Nontarget Organism Data 1882 Requirements 1883 The following represent the significant comments received on the need for 1884 and evaluation of nontarget organism studi es as proposed by EPA. Changes from 1885 the proposed rule to the final rule are also described. 1886 A. Need for Ecotoxicity Data for Indoor Uses 1887 1. Comment . Several commenters argued that there are few antimicrobial 1888 use patterns where ecological effects information would be relevant to an 1889 assessment under FIFRA because there is no expectation of environmental 1890
exposure 1891 2. EPA’s Response. As explained in the proposed rule, there is now a 1892 greater concern regarding in door uses of antimicrobi als because those uses can 1893 lead to environmental exposure when they go down-the-drain. The Agency and 1894 the scientific community have more recently become concerned with 1895 pharmaceuticals and personal care products (PPCPs), which are now recognized 1896 as environmental contaminant s. A subset of these PPC Ps includes antimicrobial 1897 pesticide products, some of which are bei ng detected in various environmental 1898 compartments/media [e.g., surface water and WWTP biosolids]. As discussed in 1899 the proposed rule (73 FR 59407), these findi ngs are notable, because many of the 1900 antimicrobial pesticides detected are r egistered for only indoor use patterns. 1901 There are many uses for which a high potential for environmental exposure 1902 exists, especially outdoor uses such as wood preservatives, ballast water 1903 treatments, antifoulant paint s and coatings, aquatic area s, and others. These 1904*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 83 of 234 uses may require a more extensive data set that could include acute and chronic 1905 tests in both freshwater and saltwater, and possibly in the sediment as well as the 1906 water column. If the effluent from a WW TP is likely to contain an antimicrobial 1907 pesticide, or if the antimicr obial is likely to partition to the sludge that is derived 1908 during the treatment process, then indoor uses could require additional testing to 1909 further characterize the hazard and the risk. 1910 B. Transformation Products 1911 1. Comment. Several commenters question ed, how a registrant would 1912 determine if “transformation products” w ould need to be tested? With regard to 1913 the criteria for when testing is r equired on transformation products, another 1914 commenter stated their belief that any data developed to assess the potential risk 1915 to nontarget organisms should be devel oped with the appropriate residue of 1916 concern (ROC) (i.e. degradation product, me tabolite, or TGAI) rather than always 1917 testing with the TGAI. St ill another commenter asked how would EPA determine 1918 that the transformation produc ts are “more toxic, persi stent, bioaccumulative or 1919 have been shown to cause adverse effect s in mammalian or aquatic reproductive 1920 studies?” Finally, a commenter reques ted that EPA should explain what is 1921 considered “stable” in t he environment in proposed te st note 3 to the proposed 1922 nontarget organism t able in § 158.2240. 1923 2. EPA’s Response. The Agency evaluates the need for nontarget 1924 organism testing of transformation products on a case-by-case basis, using 1925 several sources of information, which in cludes, most importantly, environmental 1926 fate data. EPA proposed to requi re nontarget organism testing of 1927*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 84 of 234 transformation/degradation products or leachate residues in proposed § 1928 158.2240(a)(3) and (4). To respond to th is comment, EPA also considered a 1929 similar comment on transformation/degradati on products or leachate residues for 1930 environmental fate testing (see Unit XI V.B). In response to these comments, 1931 EPA determined to clarify and revise the criteria for testing of 1932 transformation/degradation products and leachate resi dues for nontarget plant 1933 and organisms, and environmental fa te, (§ 158.2250(b), 158.2240(a)(3), and 1934 158.2280(a)(2)) to read as follows: 1935 Data on transformation/degradation products or 1936 leachate residues of the parent compound are also 1937 required to support registration, if the Agency 1938 determines that the 1939 transformation/degradation/l eachate products meet 1940 one of the following criteria: 1941 (i) More toxic, persistent, or bioaccumulative than the 1942 parent, 1943 (ii) Have been shown to cause adverse effects in 1944 mammalian or aquatic reproductive studies, or 1945 (iii) The moiety of concern (i.e., functional group in the 1946 parent chemical molecule that imparts adverse 1947 effects) remains intact. 1948 1949 As explained in Unit XIV.B environm ental fate studies provide information 1950 on the stability and persistence of the acti ve ingredient and degradation products 1951 in the various environmental media. If the environmental fate studies on the 1952 parent indicate the transformation/degradati on product(s) is, for example, more 1953 persistent in soils, then it is possible t hat nontarget plants or animals could be 1954 exposed to the degradate. Once the transformation products and the 1955 environmental compartment in which they occur are identified, then the available 1956*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 85 of 234 toxicology data (e.g., reproduction test s, developmental tests, non-rodent chronic 1957 studies) are reviewed to determine toxicity. 1958 After reviewing all available information, then EPA would use these criteria 1959 to determine if ecological effects data on the transformation/ degradation products 1960 or leachate residues are required for ei ther nontarget organisms or nontarget 1961 plants. EPA believes that nontarget pl ant protection data may sometimes be 1962 needed when the Agency begins conducting spec ies-specific endangered species 1963 assessments for antimicrobial pesticides. 1964 EPA does not use the term “residue of concern (ROC)” in the final 1965 Nontarget Organisms Data R equirements Table. Instea d, the appropriate test 1966 material(s), such as TGAI, degradate, or TEP, is specified in the data 1967 requirements table in § 158.2240. This appr oach is also used for the conventional 1968 nontarget organism table in par t 158. Generally, for ecological testing, the TGAI 1969 testing is performed first, and then addition al testing on a tr ansformation product 1970 may be required based on the process described above. Depending on how fast 1971 a substance decays, a nontarget organism or plant could actually be exposed to a 1972 mixture of the parent and one or more degradation/transformation products. 1973 C. Test note 7 to the Nontarget Organism Table and Wood Preservatives 1974 1. Comment. Proposed test note 7 to the proposed nontarget organism 1975 data requirements table in § 158.2240 specif ies the triggers for requiring typical 1976 end-use product (TEP) testing for the ac ute freshwater invertebrate study and 1977 acute freshwater fish study. A comment er asked whether, even though, the wood 1978*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 86 of 234 preservatives use pattern is specified as “NR,” could the TEP testing be required 1979 because of the triggers in test note 7. 1980 2. EPA’s Response. Proposed test note 7 also triggered the testing for 1981 the TEP acute estuarine and marine organism s toxicity testing. EPA agrees that 1982 the combination of “R”s, “CR”s, “NR”s and the current structure of proposed test 1983 note 7, is confusing and that clarification is needed. 1984 The data requirements for TEP test ing and proposed test note 7 was also 1985 considered in light of the Agency’ s recent determination based on comments 1986 received (see Unit VI.B) on EPA’s curr ent practice of conducting risk 1987 assessments for wood preservatives based on land-only versus a land and 1988 aquatic predetermined use pattern. All wood preservative risk assessments will 1989 now be performed considering that the treated wood could end-up either on the 1990 land or in the aquatic environment. As prev iously discussed, there are multiple 1991 pathways for wood preservative degradates and/or leachates to reach surface 1992 water. EPA has also determined to c onduct a down-the-drain assessment for all 1993 appropriate use patterns which would incl ude wood preservative s, and antifoulant 1994 paints and coatings (see Unit XV.A). For wood preservatives, these 1995 determinations mean that additional ecol ogical testing is required to conduct an 1996 ecological risk assessment, and the following changes are made to the wood 1997 preservative testing column: 1998

 Acute freshwater invertebrates toxi city (TEP testing): change from “NR” 1999 to “CR”; 2000

 Acute freshwater fish toxicity (T EP testing): change from “NR” to “CR”; 2001*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 87 of 234  Acute estuarine and marine organism s toxicity (TEP testing): change 2002 from “NR” to “CR”. 2003 For antifoulant paints and coatings, the determination to conduct a down2004 the-drain assessment also means that additional data could be needed for the 2005 down-the-drain assessment, and the follo wing changes have been made to the 2006 antifoulant paints and coatings testing column: 2007

 Acute freshwater invertebrates toxi city (TEP testing): change from “NR” 2008 to “CR”; 2009

 Acute freshwater fish toxicity (T EP testing): change from “NR” to “CR”; 2010

 Acute estuarine and marine organism s toxicity (TEP testing): change 2011 from “NR” to “CR”. 2012 EPA believes that simplifying the dat a requirements that reference test 2013 note 7 to the final Nontarget Organism Table in § 158.2240(c) so that these 2014 requirements are CR for all use patterns is clearer, and also closer to the 2015 suggestions made by the commenter in their suggested nontar get organism data 2016 requirements table. Their suggested t able was predominantly “CR” for aquatic 2017 uses. Therefore, in this final rule, test note 7 triggers the “CR” studies. 2018 However, changing all the use patterns to “CR” for the TEP studies means 2019 changing the “R” proposed for the aquatic use, and industrial processes and water 2020 systems use patterns for the acute freshwat er invertebrates toxicity study and the 2021 acute freshwater fish toxicity study, to “ CR.” To account fo r this change proposed 2022 test note 7 to the prop osed nontarget organism tabl e in § 158.2240 has been 2023 revised to include an additional trigger (7 (iv)): Data are required when “the end- 2024*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 88 of 234 use antimicrobial product will be applied directly into an aquatic environment.” 2025 EPA believes that the implicat ions of this trigger ar e equivalent to the “R” and 2026 essentially this is a non-change. These changes are summarized below for both 2027 the aquatic areas and industrial proce sses and water systems testing column: 2028

 Acute freshwater invertebrates to xicity (TEP testing): change from “R” 2029 to “CR”; 2030

 Acute freshwater fish toxicity (T EP testing): change from “R” to “CR”; 2031

 Acute estuarine and marine organism s toxicity (TEP testing): no 2032 change. 2033 Nontarget organism toxicity testi ng of the TEP should be infrequently 2034 required for the antifoulant paints and coat ings use pattern because for this use 2035 pattern, the TEP could be the paint. Bec ause the testing for aquatic organisms is 2036 done in water, the test material must be soluble in water, or made soluble by 2037 addition of an appropriate solvent, if one ex ists, or other appr opriate mechanical 2038 methods. Paint is not soluble and there may not be a way to make it soluble. 2039 Since these studies are often run in gla ss aquaria, the paint could coat the sides 2040 of the glass and the test animals themselves . The paint could ruin test equipment 2041 by clogging lines and injection nozzles. Therefore EPA has added a new test 2042 note 5, which is replacing proposed te st note 5 to the proposed nontarget 2043 organism in § 158.2240. New test note 5 to the final Nontarget Organism Table in 2044 § 158.2240(c) states that an applicant should request a waiv er if the TEP cannot 2045 be tested. 2046*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 89 of 234 EPA also notes that a test note s pecifying the number of species to be 2047 tested was omitted in the proposed rule fo r the TEP testing for acute freshwater 2048 fish toxicity. This test note is needed for clar ity. Test note 3 to the final Nontarget 2049 Organism Table in § 158.2240(c) has been added to the line for acute freshwater 2050 fish toxicity. 2051 D. Acute and Chronic Toxicity Data 2052 2053 1. Comment. A commenter argued that it is essential to have both acute 2054 and chronic toxicity test results for at leas t one freshwater invertebrate, vertebrate, 2055 and plant species, and at least one marine/ estuarine invertebrate, vertebrate, and 2056 plant species. 2057 2. EPA’s Response. EPA proposed to require acute tests for both a 2058 coldwater and warmwater freshwater fi sh, an invertebrate, and one or more 2059 aquatic plants. For marine/estuarine species, for most use patterns, EPA 2060 proposed to conditionally require acut e testing with a fish and two aquatic 2061 invertebrate species, including a bivalv e, when the Agency believes there is a 2062 potential for the active ingredient or a potentially toxic degradate to reach the 2063 estuarine/marine environment through transpor t (e.g., leaching, runoff) from the 2064 treatment site. In such a situati on, chronic testing with one or more 2065 marine/estuarine species also may be requi red if the Agency bel ieves that chronic 2066 exposure is likely. These studies also are required for those uses where the 2067 pesticide product is applied directly in to the marine/estuarine environment. 2068 As to chronic testing EPA proposed to require the fish early life stage and 2069 the aquatic invertebrate life-cycle studies for the industrial processes and water 2070*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 90 of 234 systems (once-through), antifoulant coat ings and paints, and aquatic areas use 2071 patterns. At that time, EPA also proposed to conditionally require the same two 2072 studies for the low environm ental grouping (now called the all other use patterns 2073 category) and wood preservatives. 2074 However, based on this and other comments, EPA has re-evaluated the 2075 nontarget organism data needed for a regist ration decision and concluded that 2076 additional acute and chronic data are needed. See Units V.B, X.C, and XIV.F for 2077 discussions on the rationale for and descriptions of the changes. 2078 EPA does not require chronic testing for plants. Plant species encompass 2079 many different life spans. Phytoplankt on reproduce quickly and have extremely 2080 short life spans. Annuals live for 1 year. Many perennials do not actually live for 2081 multiple years, but reproduce from seeds year after year. The plant species that 2082 live the longest would be woody species, such as trees. EPA does not believe 2083 that antimicrobial use patterns impact terrestrial areas such that chronic 2084 exposures occur: To EPA’s knowledge, no adverse chronic effects caused by 2085 pesticides have been documented on plants. Any effect on terrestrial plant 2086 species has been categorized as an acute e ffect and would be covered by current 2087 testing procedures. Chronic effects of aquatic plants are covered by the acute 2088 testing guidelines. Algae is used as the pr imary test species for the acute testing 2089 of aquatic plants. The testing is bas ed on growth parameters and the tests 2090 normally run for periods of time that would include several generations of the 2091 algae. The results from the acute algal st udies would be similar to those obtained 2092*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 91 of 234 from chronic testing in other species, and could be used to assess any chronic 2093 effects to aquatic plant species. 2094 E. Avian Studies 2095 1. Comment . In proposed test note 4 to the proposed nontarget organism 2096 table in § 158.2240, which triggers the avi an dietary study, EPA specified a trigger 2097 of 100 mg ai/kg (milligrams active ingredi ent/kilogram) for additional testing. A 2098 commenter requested information on why this trigger was selected. The 2099 commenter also claimed that EPA could use exposure tools to conduct an initial 2100 assessment based on Tier 1 data, and then trigger additional testing based on 2101 risk. 2102 2. EPA’s Response . OPP has long used this value as an indication of 2103 toxicity to birds. As specified in 40 CFR 156.85(b)(3), any pesticide (including 2104 conventional pesticides) that is intended for outdoor use with an avian acute oral 2105 LD 50 of 100 mg ai/kg or less requires a precautionary label st atement that the 2106 pesticide is toxic to birds. EPA believes that if 100 mg ai/kg is appropriate to 2107 trigger a precautionary label statement, then it is also appropriate to use as a 2108 trigger for testing. Therefore, if the avian oral acute toxicity study indicates an oral 2109 LD 50 of 100 mg ai/kg or less, then an avian dietary study is required. 2110 In the proposed rule, for the avian dietary toxicity study, EPA proposed to 2111 require testing on two species for the aquat ic areas and to conditionally require 2112 testing on one avian species for all of the other use patterns. The comments 2113 reviewed and evaluated by EPA on avian toxicity testing included the 2114 commenter’s suggested data requirements table for nontarget organisms, which 2115*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 92 of 234 specified “CR” for all avian testing. EPA agrees with the comment er that “CR” is 2116 appropriate for the avian dietary toxicity and avian reproduction studies for all use 2117 patterns. This simplifies the test not es and with the appropriate triggers EPA 2118 would be able to require the needed testing. 2119 The following changes have been made to the aquatic areas column: 2120

 Avian dietary toxicity: change from “R” to “CR”; 2121

 Avian reproduction: change from “R” to “CR”. 2122 Test note 4 to the final Nontarget Organism Table in § 158.2240(c) triggers 2123 the avian dietary toxicity study based on t he results of the avian acute toxicity 2124 study. For the avian dietar y study, testing in a second species would be triggered 2125 based on the results of the avian dietary test ing in the first species. Since the 2126 second test species will be required based on the results of the first species 2127 proposed test note 5 is no longer needed and is being removed. Test note 6 to 2128 the final Nontarget Organi sm Table in § 158.2240(c) would trigger the avian 2129 reproductive study based on one or more of f our specific criteria: There were no 2130 revisions to these criteria from the proposed rule to the final rule. 2131 F. Water Quality Criterion 2132 1. Comment. A commenter argued that the registrants of any 2133 antimicrobial pesticide that has the potential to be dischar ged either directly or 2134 indirectly to surface water should be r equired to supply any additional data 2135 needed to derive a water quality criteri on for the pesticide in question. 2136 2. EPA’s Response

. As discussed in the conventionals Response to 2137 Comments Document in docket EPA-HQ-OPP-2004-03 87 (p. 104) at 2138*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 93 of 234 http://www.regulations.gov , the Agency’s pesticide regi stration process, including 2139 its data requirement regulations, adequat ely considers the endpoints that are 2140 protected under the Clean Water Act (CWA) as administered by the Office of 2141 Water (OW). When acceptable data are ava ilable, OPP uses these data in its risk 2142 assessment process. 2143 The purpose of a water quality criter ion under the CWA is to determine the 2144 level at which a water body may be at risk for environmental damage. The 2145 purpose of certain data requirements for pe sticide registration is to allow the 2146 Agency to determine the ecological risk of using a pesticide. Thus, these program 2147 offices within EPA have similar goals. While EPA has developed guidelines for 2148 developing Water Quality Criteria (WQC), the Agency has also recognized that 2149 WQC can be developed with a more limited data set. 2150 Pesticide registration data are valuable in assessing water quality risks. As 2151 noted in EPA’s 2005 Response to Comm ents Document on the conventional 2152 pesticides, EPA’s OW and OPP together developed aquatic life benchmarks for 2153 71 pesticides or pesticide degradation produ cts for States to use to establish 2154 targets for safe levels of pestici des for aquatic plants and animals. The 2155 benchmarks are derived from data submitted to EPA for pesticide registration. As 2156 of April 18, 2011, there are 242 pestici de chemicals with aquatic benchmarks on 2157 EPA’s website 2158 ( http://www.epa.gov/oppefed1/ecorisk _ders/aquatic_life_benchmark.htm ). 2159 G. Sediment Testing 2160*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 94 of 234 1. Comment. The commenter asserted that EPA did not consider the 2161 environmental fate of a compound (suc h as the tendency of a chemical to 2162 absorb/desorb) when considering the need for sediment testing. 2163 2. EPA’s Response. EPA disagrees with this co mment. Test notes 17 and 2164 18 to the final Nontarget Organism Tabl e in § 158.2240(c) trigger the sediment 2165 studies based on the results of the aerobi c soil or aquatic metabolism studies and 2166 knowledge of the physical/c hemical properties which ex press the environmental 2167 fate of the antimicrobial pesticide chem ical. The soil partition coefficient (K d ) is 2168 used as an expression of binding capability of the chemical to sediments. The 2169 Agency’s justification for using K d > 50 as a criterion for requiring sediment testing 2170 is that this value would capture those chemicals with about 80 percent adsorption 2171 to sediments (relative to organic carbon). 2172 The octanol-water partition coefficient (K ow ) and the soil organic carbon2173 water partition coefficient (K oc ) also are used by EPA as part of its decision 2174 process. Both values are frequently more available than either the K d or half-life 2175 values. Test note 17, the tr igger for requiring an acute sediment study, considers 2176 all four of these values. 2177 Next, as explained in test note 18, t he chronic sediment study is triggered 2178 based on the results of the acute sediment study as well as a re-examination of 2179 the K ow, , K oc , and K d . 2180 XII. Discussion of Key Comments on Nontarget Plant Protection Data 2181 Requirements 2182*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 95 of 234 The following represent the signi ficant comments on the need for and 2183 evaluation of nontarget plant protecti on studies as proposed by EPA. The 2184 changes from the proposed rule to final rule are also described. 2185 A. Triggers for Higher-Tiered Plant Studies 2186 1. Comment. One commenter asked EPA to ex plain the criteria used to 2187 trigger higher-tiered plant studies bas ed on the results of the algal studies. 2188 2. EPA’s Response . The criteria to trigger hi gher-tiered plant studies are 2189 specified in proposed test notes 2 a nd 5 to the proposed nontarget plant 2190 protection table in § 158.2250. A toxicity level (EC 50 <1 ppm) indicates that the 2191 antimicrobial pesticide would have seri ous adverse affect(s) on algae at low 2192 concentrations. This could have serious consequences to nontarget algae 2193 species. Therefore, at this toxicity leve l, additional higher-tier ed testing is required 2194 to further characterize the potential adver se affects to aquatic plants. EPA is 2195 retaining the toxicity trigger of <1 ppm in test note 5 to the final Nontarget Plant 2196 Protection Table in § 158.2250. 2197 In evaluating proposed test not e 2 to the proposed nontarget plant 2198 protection table in § 158.2250, EPA has considered the commenter’s suggested 2199 table for nontarget plants. For the seedling emergence study, the commenter 2200 used “CR” for most use patterns and suggested that the seedling emergence 2201 study should only be required “when environm ental exposure is likely to result 2202 under normal usage conditions as dete rmined by appropriate assessment 2203 methods.” Another comment (see res ponse to comment 140.27 in the Response 2204*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 96 of 234 to Comments Document in the docket at http://www.regulations.gov ) advocated 2205 for the use of a Risk Quotient (R Q) approach for assessing plants. 2206 Based on this evaluation, EPA believes using “CR” for the seedling 2207 emergence study when triggered by a leve l of concern approach (RQ approach) 2208 would provide EPA with the required data when needed. Test note 2 to the final 2209 Nontarget Plant Protection table in § 158. 2250 now reads as: Data are required if 2210 the risk quotient from any aquat ic plant growth Tier II study exceeds a level of 2211 concern for aquatic plants. 2212 However, test note 2 also triggers the aquatic plant growth (aquatic 2213 vascular plant) study, and is still the appropriate trigger for that study. Today, 2214 EPA is adding a new test note 10 to the final Nontarget Plant Pr otection Table in § 2215 158.2250, which will read the same as the original, proposed test note 2 to the 2216 proposed nontarget plant protec tion table in proposed § 158.2250. 2217 B. Alternative Format for Plant Protection Data Requirements Table 2218 1. Comment. In the comments submi tted to EPA, the commenters 2219 suggested an alternate antimicrobial plant protection data requirements table. 2220
2. EPA’s Response

. The table suggested by the commenter is not adequate to evaluate the 2221 hazards and risks to nontarget plants from antimi crobial pesticides. The suggested table did not 2222 include test guideline numbers, changed and reduced the number of use patterns, and proposed that 2223 all ecotoxicity plant studies are either not require d or only conditionally required. The commenter 2224
contends that there are no circumstances where ecological effects plant data are relevant for 2225 antimicrobial pesticides, and that indoor uses shoul d not be subject to environmental exposure or 2226 nontarget plant species risk assessments. EPA disagrees with many asp ects of these comments 2227 and the suggested ecotoxicity data requirements table for plant species. 2228*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 97 of 234 As previously discussed in the preamble to the proposed rule (73 FR 59406-7) and in 2229 Units III and V of this rule, EPA disagrees that e xposure for nontarget plants should be presumed 2230 to be minimal or nonexistent for antimicrobials app lied indoors, or that tests are not required if the 2231 test organism is the target species for the pes ticide (see testnotes 1 and 2 to the commenter’s 2232 suggested table). Moreover, there are many outdoor uses of antimicrobials that are not addressed 2233 in the commenter’s suggested table. FIFRA ma ndates that EPA conduct a risk assessment for any 2234 uses for which exposure may occur in the various environmental compartments/media. Those 2235 risks are assessed separately for the various taxa including plants, categories (e.g., freshwater, 2236 saltwater), and short-term (i.e., acute) and long er-term (i.e., chronic) exposures. Assessing these 2237 potential risks necessitates having an appropriate ecotoxicity da ta base for plant exposure and 2238 toxicity. This can only be accomplished by re quiring plant studies for the initial assessment. A 2239 tiered approach cannot be driven solely by risk quo tients derived from a Tier 1 study. The fact that 2240 an acute risk quotient for a plant species does not exceed a level of concern for acute risk does not 2241 imply that a chronic risk does not exist or that da ta are not needed to assess that risk. The trigger 2242 for a chronic test is more likely driven by th e frequency, duration, or magnitude of the chronic 2243 exposure and the environmental properties of the pesticide. For example, plants might be 2244 subjected to repeated low-level exposure that is not acutely lethal but which may impact 2245 reproductive success and plant growth. 2246 EPA disagrees that the test substance for pl ant studies (in the commenter’s table) should 2247 be identified simply as the “residue of concern (R OC).” In its proposed nontarget plant data 2248 requirements table, EPA specified the test materi al (TGAI, TEP) to be used for each study. The 2249
test substance determination is made after reviewing the re quired environmental fate and 2250 physical/chemical properties data and any other available informati on (e.g., open literature, closely 2251 related chemicals) to determine the substance of concern for exposure of non-target plants and 2252 organisms. For example, if an applicant can ad equately demonstrate that the TGAI dissipates so 2253*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 98 of 234 rapidly that there would be no acute or chroni c exposure, TGAI testing may be waived, and 2254 instead degradate testing may be required. 2255 The commenter also omitted all guideline numbers from its suggested data table. At this 2256 time, all data requirement tables in 40 CFR part 158 have guideline numbers since this is a method 2257 of providing information to applicants. A pplicants are not required to use these guidance 2258 documents, but are encouraged to use these test guidelines when developing data. Since these 2259 guidelines have been developed via a rigorous process, as discussed in the preamble to the 2260 proposed rule [59387], “they represent the recommend ed approach to developing high-quality data 2261 that should satisfy EPA’s data needs for risk assessment.” 2262 XIII. Discussion of Key Comments on Applicator and Post-Application 2263 Exposure Data Requirements 2264 The following represent the signific ant comments received on the need for 2265 and evaluation of applicator and post-applic ation exposure studies as proposed 2266 by EPA. Changes from the proposed rule to the final rule are also described. 2267 A. Consistency With OSHA and Other Standards 2268 1. Comment. A commenter asserted that EPA should be consistent with 2269 OSHA and other standards with regard to exposure limits and handling practices, 2270 and incorporate the OSHA standards into risk assessment evaluations. The 2271 commenter also asked that when EPA be lieves that an OSHA or American 2272 Conference of Governmental and Industr ial Hygienists (ACGIH) standard is not 2273 adequately protective for an antimicrobi al, that the finding should be 2274 substantiated. 2275 2. EPA’s Response. The OSHA workplace standard is the permissible 2276 exposure limit (PEL). When developing a PEL, OSHA considers the toxicity of the 2277 chemical, often using data from the open liter ature as well as t he feasibility that 2278*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 99 of 234 exposures could be reduced to the PEL us ing process modifications, engineering 2279 controls and personal protective equipment (PPE). Approximately 500 PELs have 2280 been established. 2281 The ACGIH establishes health–based Threshold Limit Values (TLVs), 2282 which are non-governmental guidelines used by professional industrial hygienists 2283 in making decisions about safe levels of exposure to a chemical substance in the 2284 workplace. The TLVs were established for some chemicals as early as 1946 and 2285 they are updated on a regular basis as new health effects information becomes 2286 available. Like the OSHA PELs, the TLVs are based on health effects data from 2287 the open literature. Howeve r, unlike the OSHA PELs, feasiblity issues are not 2288 considered in establishing TLVs. TLVs are not available for most pesticide 2289 chemicals. 2290 However, for those pesticide chemicals with both TLVs and RfCs 2291 (Reference Concentrations are establis hed by OPP based on studies submitted 2292 by the registrants), the RfCs are often lower than the TLVs. There could be 2293 several reasons for such differences. T he data used by OPP is submitted by the 2294 pesticide registrants and the toxicity databas e is composed of animal studies. So, 2295 uncertainty factors are used to derive t he RfCs (exposure limits). Instead of 2296 animal studies, ACGIH prefers to rely on epidemiology studies/case reports of 2297 human, particularly worker, exposures from the literatur e and on professional 2298 judgment. 2299 For example, ACGIH and OPP establis hed different inhalation limits for 2300 formaldehyde based on slightly different in terpretations of the same literature 2301*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 100 of 234 studies. The TLV for formaldehy de is 300 ppb and the OPP “RfC” for 2302 occupational uses is 100 ppb. Although the TLV is greater than the “RfC,” 2303 ACGIH does acknowledge in their TLV docum entation that irritation can occur in 2304 some workers at levels of 100 to 300 ppb. 2305 EPA believes that an existing OSHA or ACGIH standard should be 2306 considered as part of EPA’s hazard evaluation. However, before using an OSHA 2307 or ACGIH standard, EPA would review the standard and the health effects 2308 (toxicology) documents supporting the st andard’s development to determine if 2309 EPA believes that the standar d provides adequate protection. EPA agrees with 2310 the commenter that EPA’s evaluation of an existing OSHA or ACGIH standard 2311 should be part of its hazard evaluation documentation. 2312 In its proposed rule, EPA proposed in the applicator exposure table (40 2313 CFR 158.2260(a)(1)) and t he post-application exposure table (40 CFR 2314 158.2270(a)(1)) to use established workpl ace standards, such as OSHA’s. The 2315 proposed language was: 2316 If EPA determines that industrial standards, such as 2317 the workplace standards se t by the Occupational 2318 Safety and Health Administration, provide adequate 2319 protection for a particular pesticide or a particular use 2320 pattern, applicator exposure data may not be required 2321 for that pesticide or the use pattern. Applicants should 2322 consult with the Agency on appropriate testing before 2323 the initiation of studies. 2324 2325 In addressing this comment, EPA realiz ed that this proposed language is 2326 misplaced and also needs some textual modification. As discussed above, an 2327 OSHA PEL or ACGIH standard is part of hazar d evaluation. If the PEL or TLV is 2328 determined to be adequate to fulfill EPA’s se lection of a toxicity endpoint, then the 2329*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 101 of 234 types and number of toxicity studies that may be required is impacted, not the 2330 need for exposure data. Therefore, EPA has removed the language originally 2331 proposed for § 158.2260(a)(1) and § 158.2270(a)(1 ) concerning use of OSHA 2332 standards. With modifications, the following language appears in the final 2333 Toxicity Table, § 158.2230(e): 2334 If EPA determines that industrial standards, such as 2335 the workplace standards se t by the Occupational 2336 Safety and Health Administration, provide adequate 2337 protection for a particular pesticide or a particular use 2338 pattern, additional toxicity data may not be required 2339 for that pesticide or the use pattern. 2340 2341 B. Poisoning Incident Data 2342 1. Comment. “Poisoning incident data” should not be incorporated into 2343 this regulation unless the EPA can provide cr iteria to trigger the need for exposure 2344 data based on poisoning incidents. R egulating based upon anecdotal reports of 2345 “poisoning” is not appropriate. 2346 2. EPA’s Response . Both proposed § 158.2260(b) and § 158.2270(b) 2347 contained the following trigger for requiri ng exposure data: “Scientifically sound 2348 epidemiological or poisoning incident data indicate that adverse health effects 2349 may have resulted from handling of t he pesticide." EPA understands that 2350 anecdotal reports may or may not indicate a cause-effect relationship, i.e., that 2351 adverse health effects may or may not have resulted from exposure to the 2352 pesticide. EPA agrees that anecdotal repor ts may not substantiate a clear dose 2353 response relationship of “poisoning,” and th erefore, when not s ubstantiated, are 2354 not appropriate for regulatory endpoint s. In-depth information on the dose 2355 response is the critical information needed for regulatory endpo ints, and poisoning 2356*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 102 of 234 incident data rarely include this information. However, EPA’s in tention was to use 2357 scientifically credible information as a tr igger for requiring ex posure data. Based 2358 on this comment, EPA has revised the toxicity triggers in § 158.2260 and § 2359 158.2270 to clarify that pois oning incident data must have a clear cause effect 2360 relationship to indicate that adverse health effects may have resulted from 2361 exposure to the pesticide. 2362 C. Use of Existing Post-Application Exposure Data 2363 1. Comment. A commenter argued t hat there is a signi ficant amount of 2364 post-application exposure data available that should be considered/used before 2365 requiring data under FIFRA. 2366 2. EP A’s Response . EPA acknowledges that there are existing exposure 2367 data either in the literatur e, or via other government al organizations such as 2368 OSHA, or academia, etc. When ava ilable and appropriate, EPA uses such 2369 exposure data and/or informa tion in its risk assessments. For example, the risk 2370 assessments for both chlorine dioxide and ethylene oxide relied heavily on the 2371 workplace air concentration monitoring data available in OSHA’s Chemical 2372 Exposure Health Database (CEHD), forme rly known as, Integrated Management 2373 Information System (IMIS). To a ccess CEHD, users navigate on the OSHA 2374 homepage ( http://osha.gov/) to Chemical Exposure Health Data under the Data 2375 and Statistics section towards the bottom right of the page. Users can search 2376 CEHD by Establishment Name, State, Zi p Code, Year Range, Standard Industrial 2377 Classification (SIC), North American Industrial Classification System Code 2378*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 103 of 234 (NAICS), Chemical Abstracts Service Nu mber (CAS), Chemical Name, or Result 2379 Range. 2380 Applicants who are aware of exis ting data that could fulfill a data 2381 requirement should submit the data to EPA. EPA will consider the 2382 appropriateness and robustness of the data, and, if appr opriate, will use the data 2383 in the Agency’s risk assessment. 2384 D. Soil Residue and Indoor Surf ace Residue Dissipation Studies 2385
1. Comment. A commenter claimed that ther e is little justification for 2386 requiring the soil residue dissipation and indoor surface residue dissipation 2387 studies. 2388
2. EPA’s Response . In the proposed rule, EPA conditionally required the 2389 soil residue dissipation study for both occupational and residential scenarios. 2390 EPA agrees that the likelihood of requiring soil residue dissipation data is low for 2391 the majority of antimicrobial use patterns. The low likelihood is reflected in the 2392 “CR” designation in the proposed post- application exposure data requirements 2393 table for the soil residue dissipation st udy for both occupational and residential 2394 use patterns. No changes are needed. 2395 In the proposed rule, EPA required the indoor surface residue dissipation 2396 study for both occupational and residential scenarios. However, the likelihood of 2397 requiring indoor surface residue dissipation data is high for residential products 2398 such as antimicrobial-treated clothing and pl astic consumer items/toys, as well as 2399 direct applications such as carpet shampoos, laundry det ergents, and floor 2400*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 104 of 234 cleaners that are antimicrobial products. Therefore, the indoor surface residue 2401 dissipation study for the re sidential use sites will remain “R” as proposed. 2402 However, EPA has re-evaluated the “R” proposed for occupational use 2403 sites. When compared to residential us e sites, occupational use sites are less 2404 likely to result in the need for indoor surf ace residue dissipation data. Therefore, 2405 the data requirement for indoor surface residue data has been revised from “R” to 2406 “CR” for occupational uses. 2407 In most manufacturing se ttings, there is less contac t with surfaces than in 2408 most residential scenarios . For example, under most circumstances workers do 2409 not crawl around the floors of manufacturing plants. The need for indoor surface 2410 residue dissipation data for workers is limited by the residue distribution where 2411 contact may occur. EPA now agrees t hat the occupational use sites are less 2412 likely to result in the need for indoor surface residue dissipation data, and 2413 therefore, the “R” has been revised to “CR.” 2414 E. Non-Dietary Ingestion Study 2415 1. Comment . A commenter asserted that the proposed requirement for 2416 non-dietary ingestion is impractical and unnecessary, and, in fact, could be 2417 replaced by modeling. 2418 2. EPA’s Response. EPA agrees that the non-di etary ingestion study is 2419 impractical, as a stand-alone direct m easurement study. Non-dietary ingestion 2420 exposure (i.e., incidental or al ingestion by children) is of potential concern for 2421 treated articles or surfaces that may be a ccessed by children. For example, uses 2422 such as carpet shampoo, hardwood floor treatments, pressure-treated wood, and 2423*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 105 of 234 impregnated materials (including but not lim ited to plastic toys or treated clothing) 2424 are assessed for non-dietary exposures when to xicity criteria are triggered. In all 2425 of these instances, non-dietary ingestion exposures are estimated using residue 2426 data from the treated surface combined with activity fact ors for children’s 2427 behaviors (e.g., frequency of hand-to-mouth contact). Often, EPA models this 2428 route and pathway of exposur e using inputs from the av ailable, reliable published 2429 research. If EPA were to require data to estimate this exposure pathway, EPA 2430 would require surface residue data, rather than requiring the actual monitoring of 2431 children or having individua l registrants collecting data on frequency of hand-to2432 mouth activities, as these are not chemical-specific. Given the unlikelihood of 2433 requiring non-dietary ingestion exposure studies, EPA has removed this data 2434 requirement from the final Post-Applic ation Exposure Table as well as the 2435 accompanying test note 12. 2436 XIV. Discussion of Key Comments on Environmental Fate Data 2437 Requirements 2438 The following represent the signifi cant comments received on the need for 2439 and evaluation of environmental fate studi es as proposed by EPA. Changes from 2440 the proposed rule to the final rule are also described. 2441 A. Need for Environmental Fate Data for Indoor Uses 2442 1. Comment. Several commenters argued that the proposed 2443 environmental fate data requirements for in door uses of antim icrobials should not 2444 exceed those in part 158 for convent ional pesticide chemicals, since 2445 antimicrobials are not directly broadcast into the environment. 2446*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 106 of 234 2. EPA’s Response . As explained in the pr oposed rule, there is now a 2447 greater concern regarding indoor us es of antimicrobials because those 2448 antimicrobial uses can lead to environm ental exposure when they go down-the2449 drain. The rationale for requiring envir onmental fate data for antimicrobials 2450 mirrors that of Unit XI.A for requiring nontarget organism data for antimicrobials. 2451 There are many uses for which a high potential for exposure exists, and 2452 these uses may require a more extensive environmental fate data set that could 2453 also include aerobic and anaerobic metabolis m studies. However, such uses will 2454 typically require a much reduced first tier data set with additio nal testing triggered 2455 if the results of the r equired data indicate a potential risk that needs further 2456 characterization. 2457 B. Transformation Products 2458 1. Comment . A commenter argued that the Agency has not clearly stated 2459 when environmental fate data on the transfo rmation products would be required. 2460 Additionally, the commenter also want ed to understand the data that would be 2461 required if the subs tance degrades quickly? 2462 2. EPA’s Response . For environmental fate dat a, the Agency evaluates 2463 transformation products on a case-by-case basis, using several sources of 2464 information. First, the transformation products need to be identified. While 2465 product chemistry data can provide some information on degradates, 2466 environmental fate data provide data s pecific to a particular environmental 2467 compartment. Environmental fate studies provide information on the stability and 2468 persistence of the active ingredient and its degradation products in the various 2469*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 107 of 234 environmental media. For example, in the hydrolysis study, a half-life >30 days 2470 indicates that the substance is stable to hydrolytic processes, i.e., the substance 2471 did not degrade. Similar determinations are made based on the results of the 2472 photodegradation in soil and water st udies, and the aerobic and anaerobic 2473 metabolism in soil and water studies after review of the required fate data. 2474 Monitoring and incident data, if availa ble, also may indicate stability and 2475 persistence. There could also be envir onmental fate data conducted on a related 2476 chemical or information from the open literat ure. This analysis is critical to 2477 determining not only the need for environm ental fate data for transformation 2478 products, but also is the first step for determining the need for nontarget organism 2479 or nontarget plant data for transformation products. 2480 EPA proposed criteria to require te sting of transformation/degradation 2481 products or leachate residues in propos ed § 158.2280(a)(2) and (3). To respond 2482 to this comment, EPA also considered a similar comment on 2483 transformation/degradation pr oducts or leachate residues for nontarget plant and 2484 organism testing (see Unit XI.B). In response to these comments, EPA 2485 determined to clarify and revise the criteria for testing of 2486 transformation/degradation products and leachate resi dues for nontarget plant 2487 and organisms, and environmental fa te, (§ 158.2250(b), 158.2240(a)(3), and 2488 158.2280(a)(2)) to read as follows: 2489 Data on transformation/degradation products or 2490 leachate residues of the parent compound are also 2491 required to support registration, if the Agency 2492 determines that the 2493 transformation/degradation/l eachate products meet 2494 one of the following criteria: 2495*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 108 of 234 (i) More toxic, persistent, or bioaccumulative than the 2496 parent, 2497 (ii) Have been shown to cause adverse effects in 2498 mammalian or aquatic reproductive studies, or 2499 (iii) The moiety of concern (i.e., functional group in the 2500 parent chemical molecule that imparts adverse 2501 effects) remains intact. 2502 2503 EPA would use these criteria to dete rmine if environmental fate data on the 2504 transformation/degradation products or leachate re sidues are required. 2505 Therefore, if the environ mental fate studies on the parent indicate the 2506 transformation product(s) is, for example, more persistent in soils, then the same 2507 environmental fate data required for the parent are required for the transformation 2508 product(s). If concerns ar e identified, then higher-tiere d environmental fate and/or 2509 ecological effects data on the transf ormation/degradation product(s) would be 2510 required. 2511 It should be noted that the criteria for determining whether to assess risks 2512 from a chemical substance and/or it s degradation product s when conducting a 2513 down-the-drain analysis are different from those discussed above. Those criteria 2514 are discussed in response to comment 130.4 in the Response to Comments 2515 Document in the docket at http://www.regulations.gov

. 2516 C. Photodegradation in Soil Study 2517 1. Comment . A commenter claimed that EPA has not sufficiently 2518 explained why a photodegradation in soil study would be required if a substance 2519 hydrolyzes and its behavior is k nown from its soil profile. 2520 2. EPA’s Response . EPA proposed to require the photodegradation in soil 2521 study for only one use pattern: wood preservatives. Wood products that have 2522*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 109 of 234 been treated with wood preservatives are of ten in contact with soil, and therefore 2523 it is possible for the wood preservative c hemical, as well as its transformation and 2524 degradation products, to leac h out from the treated wood product. To understand 2525 the fate of wood preservative chemicals in soil, first require s an understanding of 2526 the soils properties. Soil profiles are descr iptions of soil properties, both physical 2527 and chemical. Examples of physical char acteristics would include: color, bulk 2528 density, and texture. Exampl es of chemical characteri stics would include: pH of 2529 the soil, organic matter content, and Cation Exchange Capacity (CEC). 2530 Depending on the soil profile , an antimicrobial pesticide can undergo chemical 2531 and/or biochemical (biodegradati on) processes. For exampl e, if the pH of the soil 2532 is less than 7, the ant imicrobial can undergo hydrolysis and become 2533 nonpersistent, or if the pH of the soil is basic, the antimicrobial could remain 2534 stable and become persistent. If the organic carbon content of a soil is high, then 2535 the soil has a high microbial populati on which facilitates the biodegradation 2536 process. Hence the nature of a soil (soil profile) is an important indicator of how a 2537 pesticide may behave in a soil. 2538 Many applicants are well aware of soil profiles, since EPA asks for the soil 2539 profile to be submitted along with the result s of the studies in soils. A number of 2540 soil profile databases are av ailable: Two of the dat abases used by OPP are one 2541 from USDA and one called CLARION. 2542 In this final rule, EPA has retained the requirement for a photodegradation 2543 in soil study for the wood preservatives use pattern. If data from the standardized 2544 soil profiles show that the chemical is likely to readily deg rade microbially or 2545*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 110 of 234 undergo redox reactions (degrade chemically ), then the photodegrad ation study in 2546 soils may not be required. EPA is adding a new test note 10 to replace proposed 2547 test note 10 to the proposed environmental fate table in § 158.2280. New test 2548 note 10 to the final Environmental Fate Table in § 158.2280(c) explains this 2549 condition for not requiring t he photodegradation in soil study. 2550 D. Aquatic Sediment Study 2551 1. Comment. A commenter claimed that E PA is unclear about the triggers 2552 that would lead to the requirement for an aquatic sediment study, and how down2553 the-drain (D-t-D) mode ling could affect the need for this study. 2554 2. EPA’s Response . Proposed test notes 5 and 13 to the proposed 2555 environmental fate table in § 158.2280 tri gger the aquatic sedim ent study for all 2556 use patterns except the aquatic areas use pattern. EPA has re-evaluated the 2557 need for the aquatic sediment study and the appropriate triggers. EPA agrees 2558 that having two triggers, both of whic h use a weight-of-evidence evaluation 2559 process, is confusing, and believes that one trigger (p roposed test note 13) would 2560 be sufficient for triggering the aquatic sedi ment study. In today’s action, EPA is 2561 removing test note 5 from the test note column for the aquatic sediment study 2562 data requirement. Based on this re-evaluat ion, EPA also believe s that the aquatic 2563 sediment study should be required for t he antifoulant coatings and paints use 2564 pattern since an antifoulant use would meet t he criteria of the tr igger in test note 2565 13, which is: “...data are required based on the potent ial for aquatic exposure 2566 and if the weight-of-evidence indicates t hat the active ingr edient or principal 2567 transformation products are likely to have the potential for persi stence, mobility, 2568*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 111 of 234 nontarget aquatic toxicity, or bioaccumulati on.” Antifoulants are released/applied 2569 directly to the aquatic environment. Thes e products are often manufactured to be 2570 persistent, and because of t he continuous release proce ss, some of the active 2571 ingredient is likely to be transferred to t he bottom of the water column and then be 2572 adsorbed to the sediment. This is likely to result in adverse effects on nontarget 2573 benthic organisms. Since this meets the triggers for requiring the study, today 2574 EPA is changing the “CR” for the aquatic sediment study for the antifoulant 2575 coatings and paints us e pattern to “R.” 2576 The aquatic sediment study provides information about the 2577 degradation/dissipation processe s under field conditions. The results of D-t-D 2578 modeling are unlikely to prov ide appropriate information to determine the need for 2579 the aquatic sediment study. The current version of the D-t-D model estimates 2580 concentrations of chemical substances in the water column downstream of 2581 wastewater treatment faci lities, but does not estimate concentrations in the 2582 sediment. 2583 G. Monitoring of Representat ive U.S. Waters Study. 2584 1. Commen t. The commenter noted that th ere is no guidance on how to 2585 conduct a “monitoring of representative US waters” study, and that EPA has not 2586 provided the criteria for triggering a “m onitoring of representative U.S. waters” 2587 study. 2588 2. EPA’s Response . The commenter is correct: EPA does not have a 2589 guideline for conducting this study. For all pesticides, such monitoring (studies) of 2590 representative U.S. waters is a very rare occurrence. If EPA were to require such 2591*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 112 of 234 a monitoring study, protocols would have to be developed to specify a great deal 2592 of information: 2593

 At which locations would the m onitoring occur, and how often would 2594 the monitoring occur? 2595

 Is the sampling for ground water, surface water, or the 2596 estuarine/marine environment? 2597

 Which chemical substances wo uld be monitored? Is just the 2598 antimicrobial (parent) to be analyzed, or would the transformation/degradation 2599 products also be analyzed? Such a protoc ol would be specific to a particular 2600 pesticide, where that pesticide is used, and where the pesticide has been 2601 detected, and could not necessarily be used for a different pesticide. 2602 For the monitoring of representative U. S. waters data requi rement, the term 2603 “residue of concern” (ROC) is currently s pecified in the Environmental Fate Data 2604 Requirements Table in the test subst ance to support column. Since the ROC 2605 would be determined during protocol devel opment, EPA is adding this information 2606 as part of a new test note 17 to the final Environmental Fate T able in § 158.2280. 2607 As stated in the preamble to th e proposed rule, a WOE approach would be 2608 used to determine if a monitoring of r epresentative U.S. wa ters study should 2609 required. The preamble to the proposed ru le discusses this aspect in more detail 2610 (73 FR 59413). EPA expects this st udy to be rarely required. 2611 H. AWPA and ASTM Methods 2612 1. Comment. A commenter argued that AWPA method E11-97 or E20-04, 2613 and ASTM Method D5108-90 “are of limited or no relevance to estimating 2614*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 113 of 234 environmental exposures” for wood preservati ves, or antifoulants, respectively. 2615 According to the commenter, the results of the ASTM method are not suitable for 2616 “estimating release rates for regulation purposes.” The comm enter believes that 2617 both methods “overestimate leach rate s and are not intended for use in risk 2618 assessments.” The commenter also provid ed information to indicate that ASTM 2619 Method D5108-90 has been replaced by ASTM D6442-06. 2620 2. EPA’s Response . Proposed test note 15 to the proposed environmental 2621 fate table in § 158.2280 triggers the spec ial leaching data requirement for the 2622 wood preservative use pattern. EPA’s intent in specifying that it would accept an 2623 ASTM or AWPA method was to allow applic ants to use these readily available 2624 protocols. However, as noted in the pr oposed testnote, protocol review was still 2625 required for some of these methods. Si nce the commenters believe that these 2626 AWPA methods are inappropriate , but have not offered al ternative methods, test 2627 note 15 to the final Environmental Fate Table in § 158.2280(c) is revised to 2628 remove the AWPA methods. Test note 12 to the final Environmental Fate Table 2629 in § 158.2280(c) is added to require protocol review. 2630 Test note 16 to the proposed env ironmental fate table in § 158.2280 2631 triggers the special leaching data require ment for the antifoulant coatings and 2632 paints. Since the commenter in dicated that the ASTM method has been 2633 replaced, EPA believes that specifying an ASTM method number in regulatory 2634 text may provide insufficient clarity, at so me point in the future . Therefore, test 2635 note 16 to the final Environmental Fate Table in § 158.2280 is revised to remove 2636*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 114 of 234 the ASTM methods. Test note 12 to the final Environmental Fate Table in § 2637 158.2280(c) is added to require protocol review. 2638 XV. Discussion of Key Comments on Down-the-Drain Analysis 2639 The following represent the signific ant comments received on the need for 2640 and performance of a Down-the-Drain ana lysis as proposed by EPA. Changes 2641 from the proposed rule to the final rule are also described. 2642 A. Changes to Down-the-Drain An alysis Based on Comments Received 2643 1. Comment . Some commenters expre ssed concern regarding EPA’s 2644 proposal to exclude antif oulants and wood preservatives from testing designed to 2645 protect POTWs and the aquatic environmen t. These commenters contend that 2646 these compounds may reach POTWs through sources such as hull blast water, 2647 landfill leachate, and centra lized waste treatment facilit ies. They think EPA 2648 should revisit this assumption to verify its accuracy. 2649 2. EPA’s Response. Based on this comment, EPA did re-evaluate its 2650 original determination to exclude antifoulant coating and paints, wood 2651 preservatives, and aquatic areas from dow n-the-drain analysis. EPA still believes 2652 that it is appropriate to exclude aquatic areas from a down-the-drain analysis. As 2653 discussed in the preamble (73 FR 59390) aquatic areas include lakes, ponds, 2654 streams, drainage ditches, and other bodi es of water. These would not be 2655 expected to result in down-the-drain re leases and are therefore unlikely to be 2656 discharged to a WWTP. 2657 Based on its re-evaluation, EPA believe s that a down-the-drain analysis is 2658 needed for the wood preservative, and ant ifoulant paints and coatings use 2659*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 115 of 234 patterns, as well as the all other use patterns category. There are a number of 2660 sources of indirect releases of antif oulants and wood preservatives to surface 2661 water via WWTPs. The Emission Scenario Document (ESD) for Wood 2662 Preservatives, which is part of the OECD Series on Emission Scenario 2663 Documents, documents numerous sources of environmental releases directly to 2664 surface water. The ESD also describes various types of wood preservative 2665 facilities where there may be environmental releases to the facility drain that 2666 subsequently drains to a WWTP. Some of the types of wood preservative facilities 2667 identified in the OECD ESD for wood pres ervatives include automated spraying 2668 plants, dipping/immersion plants, and pl ants that employ vacuum-pressure and 2669 double vacuum processes. According to this OECD ESD for wood preservatives, 2670 it is also possible for releases to se wage treatment plants to occur from some 2671 treated wood products, such as noise barriers. 2672 According to the OECD Emission Sc enario Document for Antifouling 2673 Products, in addition to the numerous source s of direct environmental releases to 2674 surface water resulting from the use of ant ifoulant paints and coatings, there is the 2675 potential for antifoulants to enter sewage treatment plants as a result of 2676 application and removal of antifoulant paints at boatyards and marinas. 2677 Thus, OPP’s Antimicrobial Division (AD) will perform a down-the-drain 2678 assessment for every product with an applic able use or exposure scenario that 2679 has the potential for waters containing antimicrobials to reach a WWTP. To 2680 perform this assessment, the Agency is r equiring data on the biod egradation of an 2681 antimicrobial pesticide and its potential toxicity to WWTP microorganisms in an 2682*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 116 of 234 activated sludge basin. For some antimicrobial pesticides, the Agency will also 2683 require the activated sludge sorption isot herm test to determi ne removal from 2684 wastewater via partitioning to activated sludge. For additional information on the 2685 changes made to the proposed environmental fate data requirements table see 2686 response to comment 134.1 in the Response to Comments Document in the 2687 docket at http://www.regulations.gov. 2688 B. Use of E-FAST Model 2689 1. Comment . According to one commenter , EPA staff indicated at the 2690 part 158, subpart W Antimicrobials Da ta Requirements Workshop held on 2691 November 6, 2008 that the E-FAST model may have been based on municipal 2692 WWTPs that received only “residential” discharges. The commenter suggested 2693 that is very unlikely and stated that according to t he E-FAST manual, the model 2694 was based on data from actual U.S. municipal WWTPs. Nearly every municipal 2695 WWTP receives discharges from many types of non-residential sources, like 2696 commercial facilities, medical facilities, institutions, and cooling water systems 2697 (which are common in commercial buildin gs). Even in smaller communities, 2698 POTWs receive wastewater from re sidential and commercial (e.g., schools, 2699 stores, restaurants, hotels/ motels, and/or medical faci lities) sources. Most 2700 municipal WWTPs also receive both pr ocess and non-process discharges from 2701 industrial facilities. Some commenter s contend that the E-FAST model is 2702 applicable as a screening-level model for all antimicrobial use patterns with 2703 discharges that are typically rinsed down- the-drain including agricultural premises 2704 and equipment, food handling/st orage establishments, residential and public 2705*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 117 of 234 access premises, medical premises and equipment, industrial processes and 2706 water systems, swimmi ng pools, and others. 2707 2. EPA’s Response. The E-FAST documentation manual indicates 2708 that the down-the-drain module was dev eloped as a screening-level model for 2709 estimating concentrations of chemicals in surface water that may result from the 2710 disposal of consumer products into household wastewater. The model 2711 developers have confirmed, however, t hat the database of WWTPs that is 2712 accessed by this module consists of domestic WWTPs that receive wastewaters 2713 predominantly from residential, commercia l, and institutiona l sources, and not 2714 solely from residential source s. In modeling releases of antimicrobial pesticides to 2715 environmental media, the appropriate data inputs, methods, and tools are 2716 dependent upon the source of the environment al releases. To assess exposures 2717 and risks to releases of antimicrobial pesti cides to surface water from residential, 2718 commercial, and institutional sources, t he down-the-drain module of E-FAST is 2719 the most appropriate tool. 2720 To assess exposures and risks to antimicrobial pesticides from 2721 manufacturing, processing, and industrial use facilities, the general population and 2722 ecological exposures from the industrial releases modul e of E-FAST is the most 2723 appropriate tool. The decision to us e the general population and ecological 2724 exposures from the industrial releases module is made on a case-by-case basis 2725 considering the availability of data requi red as inputs to the module, and the 2726 potential for significant exposure. For ex ample, a low volume use may not require 2727 use of this module. 2728*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 118 of 234 EPA agrees that the E-FAST model is applicable as a screening-level 2729 model for all antimicrobial use patterns wit h discharges that are typically rinsed 2730 down-the-drain including agricultu ral premises and equipment, food 2731 handling/storage establishment s, residential and public access premises, medical 2732 premises and equipment, industrial processes and water systems, swimming 2733 pools, and others. 2734 C. Exceedance Levels 2735 1. Comment . Some commenters questioned the justification for the 2736 following exceedance levels that were us ed by EPA to evaluate potential risks to 2737 aquatic organisms: 2738 i. Potential risks from effects to a quatic invertebrates and fish: Exceedance 2739 of the chronic concentration of concer n (COC) for 20 or more days triggers a 2740 potential for concern; 2741 ii. Potential risks from effects to aquatic invertebrates and fish: 2742 Exceedance of the acute COC for 4 or more days triggers a potential for concern; 2743 and 2744 iii. Potential risks from effects to algae: Exce edance of the COC for algae 2745 for 4 days or less may trigger a concern and is evaluated on a case-by-case 2746 basis. 2747 2. EPA’s Response . These exceedance levels and corresponding 2748 number of days of exceedance th at trigger potential for concern are those cited on 2749 page 7-7 of EPA/OPPTS/OPPT’s “Revised Draft New Chemicals Decision 2750 Guidelines Manual” dated Apr il 17, 2001. The justificati on that the potential for 2751*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 119 of 234 chronic risk to aquatic organisms may ex ist if the predicted environmental 2752 concentration (PEC) exceeds the chroni c COC and the exceedance occurs for 20 2753 days or more per year is documented on page 11 of “Int erpretive Assistance for 2754 Sustainable Futures Summary Asse ssment,” updated January 22, 2007: 2755 “...although there is a potent ial for the concentration 2756 of the chemical in the wate r to reach levels exceeding 2757 the hazardous level, the levels are not exceeded for a 2758 sufficient duration of time to induce any chronic 2759 effects. The 20-day criteri on is derived from partial 2760 life-cycle tests (daphnid chronic and fish early life2761 stage tests) that typically range from 21 to 28 days in 2762 duration. Low concern for chronic risk exists if the 2763 COC is exceeded on fewer than 20 days per year or 2764 the PEC is less than the chronic COC.” 2765 2766 EPA notes that risk is influenced by both the duration of exposure and the 2767 likelihood of that exposure occurring. Often mathematical models are used to 2768 estimate exposures and risks. There are two types of models: deterministic or 2769 probabilistic. Probabilistic modeling is a te chnique that utilizes the entire range of 2770 input data to develop a probability distribut ion of risk or expo sure rather than a 2771 single point value. The analysis identif ies the probability that the exposure 2772 exceeds the COC and for what timeframe. Determini stic modeling is based on 2773 select input data that result in a singl e point estimate. The estimate either 2774 exceeds or does not exceed the COC. Models such as E-FAST have the 2775 capability of providing either deterministic or probabilistic result s. Consequently, 2776 criteria for determining whether or not testing on aquatic organisms is required 2777 need to take into account the possibility that the estimated exposure could be 2778 modeled using either deterministic or probab ilistic modeling. T herefore, two test 2779*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 120 of 234 notes to the final Nontar get Organism Table in § 158.2250 have been revised to 2780 include a probabilistic trigger for down-t he-drain analyses, wh ile retaining the 2781 existing deterministic trigger for releases of antimicrobials t hat are expected to 2782 enter WWTPs. Test note 7 to the final Nontarget Organism Table in § 158.2250(c) 2783 triggers the acute freshwat er invertebrate toxicity study (TEP testing) and the 2784 acute freshwater fish toxicity study (T EP testing). Test note 12 to the final 2785 Nontarget Organism Table in § 158.2250(c) triggers th e fish life-cycle study. 2786 D. Evaluation of Discharges to Still Water and to Salt Water 2787 1. Comment . During the Antimicrobial Da ta Requirements Workshop held 2788 on November 6, 2008, EPA staff indicated that evaluation of discharges to still 2789 water and to salt water would be chall enging. The commenter’s argued that the 2790 E-FAST model manual suggests that t hese discharges can be readily evaluated 2791 with appropriate input data and eliminati on of the PDM (Probabilistic Dilution 2792 Model) option. 2793 2. EPA’s Response . EPA believes that the commenter misunderstood the 2794 context of the Information provided by EPA staff both in the proposed rule and at 2795 the presentation on November 6, 2008. E-FAST has two modules for estimating 2796 releases to surface water: The down-the-drain modul e, and the general 2797 population and ecological exposure from industrial releases module. 2798 When the down-the-drain module of E-F AST is run without the PDM option, 2799 the results are limited to estimates of c oncentrations in surface water downstream 2800 of domestic wastewater treat ment facilities. The dow n-the-drain module has no 2801 option for estimating concentrations in non- flowing waterbodies such as lakes, 2802*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 121 of 234 bays, estuaries, and oceans. The discussion at the November 6, 2008, Workshop 2803 focused solely on the down-the-drain module. 2804 E-FAST, however, has the capability fo r evaluating discharges to still water 2805 and to salt water from discharges to WWTPs that receive manufacturing, 2806 processing, and industrial use releases, but not from discharges to surface water 2807 via domestic WWTPs. The general popula tion and ecological exposure from 2808 industrial releases module is designed to esti mate releases to ai r, water, and land 2809 from manufacturing, processing, and industr ial use of chemical substances. The 2810 database for estimating releases to WWTP s that primarily receive wastewater 2811 from manufacturing, proce ssing, and industrial uses requires estimates of 2812 releases to environmental media from models such as ChemSTEER (Chemical 2813 Screening Tool for Exposures and Envir onmental Releases), a model developed 2814 by EPA’s OPPT or from data and calculati ons included in standard scenarios, also 2815 developed by OPPT ( www.epa.gov/oppt/exposure/ pubs/chemsteerdl.htm ). The 2816 general population and ecolog ical exposure from industrial releases module 2817 includes an option for estimating concentra tions in lakes, bays, estuaries, and 2818

oceans. 2819 E. Parameters for Down-the-Drain Analysis 2820 1. Comment . Several commenter’s argued that EPA’s approach for down2821 the-drain chemicals separates the expos ure and the effects of the assessment 2822 and subjects chemicals to similar testing requirements regardle ss of the mass of 2823 chemicals disposed in the environment. Ac cording to these commenters, the fact 2824 that EPA does not guide testing by the ex tent of environmental exposure is 2825*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 122 of 234 wasteful for ingredients which will reach the environment at low levels. Even for 2826 chemicals which are used at greater volume, the comm enters claimed that there 2827 is no proof that EPA’s pr ogram will achieve its goal without being wasteful and 2828 some commenters believe that EPA’s approa ch will likely result in significant 2829 unwarranted costs in animals, time, and dollars. The commenters asserted that 2830 this will result in unnecessary loss of animals, increased costs to the consumer 2831 and will negatively affect product innovat ion as new product development will be 2832 slowed due to the extra regulatory burden. The benefit to the environment of the 2833 EPA approach, according to the commenters, is likely to be small and not 2834 commensurate with its costs. 2835 2. EPA’s Response . EPA disagrees with this comment. Three key input 2836 parameters for the Down-t he-Drain model are: 2837 i. Percent removal of antimicrobial pesticide during wastewater treatment; 2838 ii. Concentrations of concern for antimicrobial pesticides based on acute 2839 and chronic end-points for freshwater fish, freshwater invertebrates, and 2840 freshwater plants; and 2841 iii. Wastewater treatment pl ant influent volume of antimicrobial pesticide. 2842 As demonstrated in the sensitivity anal ysis of the down-t he-drain model in 2843 the document, “Four Case Studies of Anti microbial Pesticides in the Down-the2844 Drain Screening Model, Using the Pr oposed Approach for a Screening-Level 2845 Environmental Fate Assessment” (available in the docket at 2846 http://www.regulations.gov ), the amount of chemical disposed in the environment 2847 strongly influences the results of the down-the-drain model. It is possible that if 2848*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 123 of 234 the amount of chemical disposed is sm all (i.e., WWTP influent volume is low 2849 and/or high percent remova l during wastewater treatm ent), that t he predicted 2850 surface water concentration of the antim icrobial, even for a chemical of high 2851 toxicity, would not exceed the Agency’ s level of concern. Under such 2852 circumstances, higher-tier testing (envir onmental fate, ecotoxicity, and plant 2853 protection) is unlikely to be triggered. Since, higher-tier testing is triggered only if 2854 the down-the-drain model in dicates that the predict ed concentration of the 2855 antimicrobial may adversely affect aquatic organisms this reduces the number of 2856 tests required, and therefore the animals, time, and dollars. 2857 EPA also notes that two of the three key input parameters needed to run 2858 the down-the-drain model, percent remo val during wastewater treatment and 2859 wastewater treatment plant influent volume do not involve animal testing and 2860 would not lead to loss of animals. Fate tests required to determine removal during 2861 wastewater treatment via biodegradation and ads orption are inexpensive. No 2862 costs are associated with wastewater treatment plan influent volume. 2863 F. Acute and Chroni c Toxicity Endpoints 2864 1. Comment . At the Antimicrobial Data Requirements Workshop held on 2865 November 6, 2008, EPA staff indicated that chronic aquatic toxicity endpoints 2866 might not be used to evaluate antimicrobi al discharges from municipal WWTPs. A 2867 commenter argued that sinc e EPA/OW requires municipa l WWTP to conduct both 2868 acute and chronic toxicity tests regularly as conditions of CWA-regulated National 2869 Pollution Discharge Eliminat ion System (NPDES) permits, both acute and chronic 2870*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 124 of 234 endpoints should be evaluated by EPA/O PP to ensure that antimicrobial 2871 discharges will not cause toxicity in municipal WWTP effluent. 2872 2. EPA’s Response . To assess whether the proposed screening level 2873 assessment and tiered system of data requirements prov ides the data needed to 2874 assess exposure and risk of antimicrobial pesticides released to the environment 2875 via down-the-drain use patterns, the Agen cy conducted four case studies (73 FR 2876 59408-9). Based on this comment, EPA has re-evaluated the approach used for 2877 the case studies, in which the highe r-tiered data was triggered based on the 2878 results of the available dat a. To ensure that antimic robial discharges will not 2879 cause toxicity to aquatic organisms downstream of WWTP effluents requires an 2880 evaluation of both acute and chronic toxi city endpoints. This means that the 2881 chronic ecotoxicity data needs to be submi tted at the same time as the acute 2882 ecotoxicity data, so both types of studi es are available for EPA to use for the 2883 ecological risk assessment. Also see Units XV.A and B. 2884 Consequently, in the final Nontarget Organism Table in § 158.2250(c), the 2885 table descriptors for the fish early- life stage and aquatic invertebrate life cycle 2886 tests have been changed from “ CR” to “R” for the wood preservatives use pattern 2887 and the all other use patterns category. Test note 10 to the final Nontarget 2888 Organism Table in § 158.2250(c) has been modi fied to remove the trigger since it 2889 is no longer needed. 2890 XVI. Discussion of Key Comments on Residue Chemistry Data 2891 Requirements 2892*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 125 of 234 The following represent the signifi cant comments received on the need for 2893 and evaluation of residue chemistry studies as proposed by EPA. Changes from 2894 the proposed rule to the final rule are also described. 2895 A. Scope of the Residue Chemistry Data Requirements 2896 1. Comment. Several commenters found the scope of coverage of the 2897 residue data requirements in § 158.2290(b) to be vague and confusing. Further, 2898 the ACC Biocides Panel asserted that this section required data for uses for which 2899 a FFDCA section 408 tolerance is not r equired and over whic h, therefore, EPA 2900 allegedly has no jurisdiction. 2901 2. EPA’s Response . EPA is clarifying § 158.2290(b) which pertains to the 2902 scope of the residue data requirements. That section can be read as limiting the 2903 residue chemistry data requirements to pesti cide products requiring a tolerance or 2904 tolerance exemption. This apparent lim itation is inconsistent with both the 2905 preamble’s general description of the scope this subpart and the preamble’s 2906 description of the scope of the residue data requirements se ction, and is internally 2907 inconsistent with the terms of § 158. 2290(b). Various commentators noted the 2908 lack of clarity in this portion of the rule. 2909 The preamble’s general discussion of the scope of subpart W made clear 2910 that this subpart was not limited to “antim icrobial pesticides” as defined by FIFRA 2911 section 2(mm) – which excluded antimicrobi al pesticide uses subject to either 2912 FFDCA section 408 or section 409 – but xtended to among other things, 2913 “[p]esticide products for antimicrobial use in/on food” (73 FR 59385). In no way, 2914 however, did this discussion suggest or imply that the s ubpart is limited to 2915*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 126 of 234 antimicrobial uses requiring FFDCA secti on 408 tolerances or exemptions from 2916 tolerances. To the contrary, the pr eamble’s discussion of toxicity data 2917 requirements expressly notes that dat a are needed under subpart W to assess 2918 dietary risk whether or not a section 408 tolerance is required. The preamble 2919 specifically states that, although certain antimicrobial food uses are regulated 2920 under the FFDCA by FDA under section 409 and not section 408, EPA still needs 2921 data on these uses to assess dietary risk to fulfill its statutor y obligations under 2922 FIFRA section 2(bb)(2), which establishes the FFDCA section 408 safety standard 2923 as a component of the FIFRA standard for registration/cancellation for FIFRA 2924 pesticide uses that result in resi dues on food (73 FR 59394). Further, the 2925 preamble’s discussion of residue chemistry data requirements st ates that these 2926 data are needed for “direct and indirect food us es” including application to “food or 2927 water” both to assess risk and for toleranc e-setting purposes (73 FR 59401: “In 2928 addition to dietary risk assessments, resi due chemistry data are used to establish 2929 pesticide tolerance . . . .”). Finally, both the preamble’s di scussion of residue data 2930 requirements and the relevant rule text m ention antimicrobial uses that would be 2931 excluded by a limitation of t he rule to antimicrobial uses requiring tolerances. For 2932 example, both the preamble and rule text refer to “fruit and vegetable rinses,” 2933 antimicrobials “incorporated into a materi al that may contact food or feed,” and 2934 “[a]quatic uses that have the potential to result in residues in potable water” and 2935 all of these uses may not need section 408 tolerances (73 FR 59401 and 59444). 2936 Accordingly, EPA is revising § 158.2290(b) to make clear it is not limited to 2937 antimicrobial uses which need FFDCA section 408 tolerances. With some 2938*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 127 of 234 modifications, EPA is retaining in § 158. 2290(b) a non-exclusive list identifying 2939 examples of antimicrobial products covered by this section. This revision to § 2940 158.2290(b) makes clear that the residue data requirements apply to antimicrobial 2941 products that may result in residues in food or water whether or not a FFDCA 2942 section 408 tolerance is needed. Section 158.2290(b) is revis ed by replacing the 2943 opening lines of subsection (b )(1) with the following: 2944 “Residue chemistry data are required for: 2945 (1) Antimicrobial end-use products with uses that may result in 2946 residues in or on food including, but not limited to:” 2947 The first item in the list of covered uses now reads “Products that require a 2948 tolerance, tolerance exempt ion, or food additive regul ation or clearance.” The 2949 insertion of the reference to food additive regulations and clearances is consistent 2950 with the rule’s scope which is not limit ed to pesticide uses regulated under FFDCA 2951 section 408. Additionally, each of the subparagraphs listing examples of covered 2952 uses has been revised to refer to “products ” rather than “uses” for consistency 2953 and clarity. Although the subparagraphs are overlapping (i.e., a product may fall 2954 in more than one paragraph), the revised subsection now clarifies the overall 2955 scope of this section. These revisions make § 158.2290(b) consistent with the 2956 scope of the rule described in the preambl e and the scope of the toxicology data 2957 requirements. 2958 Not only are these changes consist ent with the scope of the rule as 2959 discussed in the preamble (i.e. data r equirements are not lim ited to uses needing 2960 section 408 tolerances) but the revis ed language’s focus on whether use of a 2961*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 128 of 234 pesticide may result in residues in or on food follows directly from the intent of the 2962 residue chemistry requirements as discu ssed in the preamble. There, EPA 2963 explained that the proposed requirem ents will provide information “to better 2964 estimate human dietary exposure to antimicr obial residues in or on food or feed,” 2965 “to determine the composition of the pes ticide residue and how much of the 2966 residue is present in food or animal f eed,” and to “measure how much of the 2967 residue of concern is present in food, feed, and water” (73 FR 59401). Further, 2968 the revised language is consistent with scope of FFDCA section 408 (applies to 2969 “pesticide chemical residue[s] in or on f ood”) and FIFRA (requires consideration of 2970 “residues that result from the use of a pes ticide in or on food”). It also follows 2971 directly from the existing data requirement s applying to antimicrobials in Part 161. 2972 Those regulations provide that “Residue Chemistry Data are used by the Agency 2973 to estimate the exposure of the general population to pesticide residues in food 2974 and for setting and enforcing tolerances for pe sticide residues in food or feed.” 40 2975 CFR 161.202(c)(1); see also 40 CFR 161.202(c)(2) (“results of tests on the 2976 amount of residues remaining on or in the treated food or feed are needed to 2977 support a finding as to the magnitude and id entity of residue which result in food 2978 or animal feed as a consequence of a proposed pesticide usage”); 40 CFR 161. 2979 240(14) (Residue data on indoor use of pesticide “if such a use could result in 2980 residues in food or feed”). Finally, the revised language also tracks EPA’s 2981 requirements for residue chemistry data under the current data requirements for 2982 conventional pesticides in 40 CFR part 158, subpart O. In the preamble to the 2983 proposed rule, EPA explained that t he residue data requirements for 2984*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 129 of 234 antimicrobials were adapted from the conventional data requirements in subpart O 2985 (73 FR 59401). For uses of conventi onal pesticides, other than uses in 2986 agriculture, part 158 states that “[residue ch emistry] [d]ata may be required . . . if 2987 residues may occur in food or feed as a result of the use.” (40 CFR 2988 158.1410(a)(2)). The regulation also make s clear that this requirement applies 2989 whether or not a toleranc e is needed under FFDCA sect ion 408. The regulation 2990 specifies that “most products used in or near kitchens require residue data for risk 2991 assessment purposes even thoug h tolerances may not be necessary in all cases.” 2992 (Id.) 2993 The commenters’ concern that t he residue chemistry requirements 2994 exceeded EPA’s jurisdiction under the FFDCA is addressed above in Unit IV. 2995 B. Complete Transference of the Antimicrobial into Food 2996 1. Comment . The commenter believes that additional clarification is 2997 needed concerning EPA’s statement, “in th e absence of data [the Agency will] 2998 evaluate the need for a tolerance or tole rance exemption by assuming complete 2999 transference of the chemical into food over the lifetime of the treated product.” 3000 2. EPA’s Response . Complete transference re fers to an assumption that 3001 the Agency would initially make regarding th e migration of antimicrobial residues 3002 from an impregnated food contact material to the food contacting that material 3003 over the typical use life of the antimicr obial-impregnated material . The worst-case 3004 assumption is that 100 perc ent of the antimicrobial resi dues resulting from use at 3005 the maximum registered rate transfers in to the food, which is then used to 3006 estimate a conservative dietary exposur e. If the aggregate risk calculated using 3007*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 130 of 234 this conservative assumption, from use of the antimicrobial in question, is less 3008 than EPA’s level of concern, then no m easured data are needed. If the aggregate 3009 risk meets or exceeds EPA’s level of concern, then chemical-specific data 3010 quantifying residue migration to refine this dietary exposure component may be 3011 required. To refine the exposure, the applicant may choose to perform one or 3012 more of the FDA protocols to estimate migration rate into food simulants 3013 (FDA/CFSAN, 2007, Preparatio n of Premarket Submissions for Food Contact 3014 Substances: Chemistry Recommendations (R ef. 11 to the proposed rule, in the 3015 docket at http://www.regulations.gov )). Alternatively, or subsequently, the 3016 applicant may choose to conduct a chemic al-specific nature of the residue on 3017 surfaces study and a migration study inve stigating actual impregnated materials 3018 using representative foods. 3019 C. Alternative Formats for Residue Chemistry Data Requirements Table 3020 Suggested by Commenters 3021 1. Comment. Two different commenters sugges ted two different options as 3022 alternative approaches to t he antimicrobial residue ch emistry data requirement 3023 table proposed by EPA. One of the commenters separ ated the residue chemistry 3024 data requirements into two tables , referred to as Part 1 and 2 [ACC Comment in 3025
the docket at http://www.regulations.gov ; document EPA-HQ-OPP-2008-0110- 3026 0088.10 p. 7] . The other commenter s uggested a single table format [CSPA 3027
Comment in the docket at http://www.regulations.gov; document EPA-HQ-OPP3028 2008-0110-0086.2]

. 3029 2. EPA’s Response . All three of the commenter-suggested tables had the 3030 same five “Supporting Informa tion” studies as the tabl e proposed by EPA, but with 3031*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 131 of 234 various mixtures of “R,” “CR,” and “NR.” In the final rule EPA has retained the 3032 Supporting Information secti on of the Residue Chemistry Table as proposed. 3033 EPA has adopted the commenters’ sugges tion for a tiered format. After 3034 review, EPA believes the commenters’ suggested tiered approach is more 3035 suitable to antimicrobials t han that proposed by EPA. A ll three commenter tables 3036 suggested that Tier 1 consist of a “Screeni ng-level dietary exposure assessment.” 3037 Although an applicant may opt to conduc t a dietary exposure assessment, EPA 3038 does not consider this to be a data r equirement. Applicants often conduct a 3039 dietary exposure assessment to understand the dietary risks before submitting an 3040 application to EPA. If subm itted, EPA would review the assumptions used by the 3041 applicant and compare to EPA’s modeling. If the applicant’s modeling indicates 3042 that dietary risk is likely to meet or ex ceed the Agency’s level( s) of concern, the 3043 applicant may decide to continue on to Tier 2 or 3. Therefore, EPA has not added 3044 a requirement to conduct a dietary exposure assessment. 3045 Both the Part 1 Table and the single t able suggested that Tier 2 consist of 3046 a “Refined dietary exposure assessment.” As is the case for the commenter’s 3047 suggested Tier 1 “Screening-level dietary exposure assessment,” this is optional 3048 for the applicant; therefore, EPA has not added a requirement to conduct a refined 3049 dietary exposure assessment. 3050 Both the Part 1 Table and the single t able suggested that Tier 3 consist of 3051 nature of residue on surface, bioaccumu lation, magnitude of residue, residue 3052 analytical method, and storage stability. These are each addressed individually 3053 below: 3054*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 132 of 234 i. Nature of residue on surface. The Agency agrees that this study is 3055 applicable and a valuable add ition to the data set necessary to support 3056 registration and risk assessment of antimicro bial uses on/in food-contact surfaces 3057 and impregnated materials (treated articles ). EPA has added this study into the 3058 final Residue Chemistry Data Requirem ents Table in part 158, subpart W. 3059 ii. Bioaccumulation. EPA believes that the co mmenters intended that this 3060 study apply only to fish and that the bioa ccumulation study required for ecological 3061 effects should substitute for the nature of the residue on surface study for aquatic 3062 uses or indoor/outdoor raw agricultural co mmodity uses. EPA has found that the 3063 fish bioaccumulation study is often not useful for residue chemistry purposes 3064 because characterization of fish residues is only required if the bioconcentration 3065 (of total residues) factor is > 1000. T he fish bioaccumulation study has not been 3066 adopted by EPA for residue chemistry. Of much more use to residue chemistry 3067 and retained in this final rule, are t he fish metabolism and magnitude of the 3068 residue studies in fish described in OPPTS Guideline 860.1400. 3069 iii. Magnitude of residue (MOR). Commenters proposed this study by the 3070 very general title “Magnitude of residue.” EPA considers MOR to be any study 3071 designed to quantify “how much” of the resi dues of concern will result in food, on 3072 surfaces, in water, etc., following use of an antimicrobial according to label 3073 directions. The commenters stated in a foot note to this study that, in the case of 3074 food-contact sanitizers and treated articl es, MOR would consist of a migration 3075 study. Because food-contact sanitizer and treated article uses comprise at least 3076 80 percent of all antimicrobial food us es, EPA has retained the migration study 3077*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 133 of 234 and the food-handling study by name but has moved them to a different tier. All 3078 the remaining proposed types of MOR studi es are much more rarely required due 3079 to characteristics such as the use pattern and/or physicochemical properties of 3080 the antimicrobial in question. For that reason, the followi ng have been grouped as 3081 “Higher tiered” studies in the final rule: nature of the residue in plants, nature of 3082 the residue in livestock, residue analytic al methods for tole rance enforcement, 3083 multiresidue method testing, pot able water, fish, irrigated crops, 3084 meat/milk/poultry/eggs, crop field trials, pr ocessed food or feed, and anticipated 3085 residues. 3086 iv. Residue analytical method. EPA agrees with the commenters that an 3087 analytical method for data collection is required whenever magnitude of the 3088 residue studies are required. The Agency has retained this study in the final 3089 Residue Chemistry Table. 3090

v. Storage stability. EPA agrees with the comment ers that storage stability 3091 data are required whenever magnitude of the residue studi es are required. The 3092 Agency has retained this study in the final Residue Chemistry Table. 3093 The Part 2 Table did not recommend requiring a Refined Dietary Exposure 3094 Assessment. Rather, its Tier 2 consists of studies entitled natur e of the residue in 3095 commodity, nature of the residue in liv estock, residue analytical methods for 3096 enforcement of tolerances , multiresidue analytical method, magnitude of the 3097 residue: in commodities, in water, and in meat/milk/poultry/ eggs, storage stability, 3098 and anticipated residues. EPA agrees that a ll of these studies should be required 3099 and has retained all of them in the highes t tier in the final Residue Chemistry 3100*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 134 of 234 Table. Note that two of the commenter-suggested studi es (nature of the residue 3101 in commodity and magnitude of the resi due in commodities) were considered 3102 applicable only to RACs treat ed via a fruit and vegetable rinse; whereas, the 3103 analogous EPA data requirements apply to both crop plants and metabolically3104 active RACs. The data requirements in EPA’s final rule easily subsume the 3105 studies suggested by a commenter in Part 2. The commenters feel that EPA only 3106 has authority to require residue data for RACs of plants treated by a fruit or 3107 vegetable rinse whereas EPA interprets FIFRA and FFDCA, as amended by 3108 FQPA, to mean that data ma y be required for any use if necessary to support 3109 registration of any use under FIFR A (see Units XVI.A and IV). 3110 As evidenced by the recommendation to divide EPA’s single proposed data 3111 requirement table into two tables (Par ts 1 and 2), the comm enters believe the 3112 data requirements are distinct ly different depending on the use pattern of interest. 3113 While this is sometimes the case, the Agency has f ound that there is much 3114 overlap between which studies are necessary to characterize the dietary exposure 3115 potentially resulting from a given use. This is why the test notes provide the 3116 conditions under which each study is requi red, likely to be required, or not 3117 required. EPA has historica lly and currently used a single data requirement table 3118 for each scientific discipline; doing so permits the interrelationships between use 3119 pattern, tiering, and data needs to be fully evident. 3120 The commenters did not account for data needed to estimate dietary 3121 exposure associated with uses that do not require a FFDCA section 408 tolerance 3122 or exemption (see Unit XVI.A and Unit IV). The commenters also did not account 3123*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 135 of 234 for data needed to estimate dietary expos ure from food residues inadvertently 3124 resulting from, but not limited to, dischar ges of antimicrobial -treated water from 3125 indoor industries, leaching from preserv ed lumber, or treatm ent of food crops 3126 when a public health claim is made on the label. 3127 XVII. Discussion of Key Comments on SAR and QSAR, and the OPPTS (now 3128 OCSPP) Integrated Testing Vision 3129 A. Guidance on Policies, Procedures, and Processes 3130 1. Comment . A commenter asked EPA to should provide clear guidance 3131 on its policies, procedures, and processes on the use of alternative technologies 3132 such as SAR and QSAR, and the WOE approac h. In addition, the commenter 3133 stated that EPA should also provide education and training on these approaches. 3134 2. EPA’s Response . The Agency encourages applicants to create 3135 submissions that include predictive techniques such as SAR and QSAR to fulfill 3136 data requirements. As described in the white paper to the proposed rule, entitled, 3137 “Use of Structure-Activity Relationsh ip (SAR) Information and Quantitative SAR 3138 (QSAR) Modeling For Fulfilling Data Requi rements for Antimicrobial Pesticide 3139 Chemicals and Informing EPA’s Risk Managem ent Process” (document 45 in the 3140 docket at http://www.regulations.gov) , an important part of the applicant’s 3141 submission is the rationale. The rationale, or WOE evaluation, is the part of the 3142 submission that explains the applicant’s belief as to why and how the predictive 3143 data would fulfill the data requirement. The WOE approach requires a critical 3144 analysis of the entire body of avail able data for consistency and biological 3145 plausibility. In support of a request that predictive data be considered, the 3146 applicant would need to explain why it be lieves the surrogate data or the modeling 3147*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 136 of 234 are appropriate for the intended use and are of sufficient completeness and 3148 quality, and therefor e would fulfill the data requi rement. The Agency would 3149 evaluate each submission with a WOE rati onale on a case-by-case basis. 3150 The general types of information that are considered appropriate for a 3151 WOE approach would include: 3152

• Sufficiency of data . Studies that completely c haracterize both the effects 3153 and exposure of the agent have more cr edibility and support than studies that 3154 contain data gaps. 3155

• Quality of the data . Potentially relevant studi es are judged for quality and 3156 studies of high quality are given more weight than those of lower quality. 3157

• Evidence of causality . The degree of correlation between the presence of 3158 an agent and some adverse effect is an important consideration. 3159 Regarding SAR/QSAR, the white paper to the proposed rule (p. 30) 3160 discusses the five criteria set by the OECD for evaluating a model. EPA 3161 encourages submitters to follow the est ablished criteria set by OECD, and show 3162 how the model is validated for that parti cular pesticide chemical structure as a 3163 measure of the model’s applicability. 3164 Different computer software programs ar e used to estimate/predict different 3165 hazards (see: http://www.epa.gov/oppt/sf/tools/methods.htm ). This means that 3166 predictive software models for different scient ific disciplines ar e not at the same 3167 level of development. The Agency has long standing experience in predicting 3168 (modeling) physical-chemical properties, environmental fate, ecotoxicity, and 3169 experience in predicting carcinogenesis for certain classes of chemicals. 3170*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 137 of 234 However, the Agency is still gaining experi ence to become familiar with predictive 3171 approaches that look at other human health endpoints (e.g., reproductive, 3172 developmental), which have not been widel y used at EPA. Given the different 3173 stages of predictive software development, EPA would expect to undertake a 3174 case-by-case evaluation of submitt ed WOEs. EPA encourages the use of 3175 integrated approaches that combine the knowledge from existing databases about 3176 the chemical of interest with data fr om appropriate surrogate chemicals. 3177 EPA agrees that guidance on the policie s, procedures, and processes for 3178 using alternative approaches such as SAR/QSAR is needed. EPA is developing 3179 such a guidance document for pesticides and is seeking to harmonize its 3180 approach with that of Canada’s Pest Management Regulat ory Authority. It is 3181 anticipated that the guidanc e document would be issued as a North American 3182 Free Trade Agreement guidance document by the end of 2011. This guidance 3183 document will adhere to the five OECD principles that were discussed in the white 3184 paper. Once finalized, this document will be the definitive source of information 3185 for applicants seeking to use SAR and QSAR approaches for fulfilling data 3186 requirements for pesticide registration. 3187 B. Integrating SAR/QSAR within the Data Requirements Rule 3188 1. Comments . One commenter argued that there should be an explicit 3189 statement that SAR and Q SAR can be considered to fu lfill data requirements. 3190 Another commenter had concerns on codi fying the use of SAR in 40 CFR part 3191 158, Subpart A since that would mean that “SAR/QSAR Techniques would be 3192 applicable to conventional, biochemica l and microbial, and antimicrobials 3193*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 138 of 234 pesticide chemicals.” Another comment er requested that SAR/QSAR be fully 3194 integrated within the rule. 3195 2. EPA’s Response . EPA has and will continue to consider accepting 3196 SAR/QSAR to fulfill its data requirement s on a case-by-case basis. Acceptance 3197 would be based on the information provided and most especially on the 3198 supporting rationale submitted to EPA. The Agency would evaluate the 3199 information submitted to determine if the applicant has provided information that is 3200 of sufficient quality and completeness. T he Agency notes that validation of QSAR 3201 models is necessary before the predict ions from those models can be fully 3202 integrated into the testing requirement s. To that end, QSAR models must be 3203 inclusive of pesticide toxicology data and chemical structures. Until these models 3204 become customized with pesticide information, full incorporation of predictive tools 3205 likely will be limited to a case-by-case basis. 3206 EPA agrees that if use of SAR/QSAR were to be codified in subpart A, that 3207 it would be applicable to all pesticide chemicals. At this time, EPA is not codifying 3208 the use of SAR and QSAR in subpart A. 3209 XVIII. Discussion of Key Comments on Guidelines 3210 A. Commenters’ Concerns with Guidelines 3211 1. Comment: Several commenters indi cated their belief that the current 3212 Harmonized Guidelines have signif icant problems, which include: 3213

 Lack of guidelines could create an unevenness from one company to 3214 another in how the data r equirements are applied. 3215

 Data requirements for which gu idelines are not available. 3216*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 139 of 234  Older, outdated guidelines that need revision. 3217

 Draft guidelines that need to be finalized. 3218

 Older exposure guidelines that do not include information about the 3219 Human Studies Review Board. 3220

 Guidelines that were adopted without the opport unity for public 3221
comment. 3222 According to the commenters, lack of current guidelines could create an 3223 unevenness from one company to another in how the data requirements are 3224 applied. The commenter argued that the Agency needs to provide current, 3225 consistent, and reliable guidance and standards for each data requirement. The 3226 commenters recommended that EPA should final ize all of its guidelines before the 3227 final rule is published per t he recommendation from OMB. 3228 2. EPA’s Response . EPA’s Harmonized Test Guidelines are publicly3229 available at http://www.epa.gov/ocspp/pubs /frs/home/guidelin.htm

. The 3230 Harmonized Guidelines contain recommendat ions on how to conduct a study that 3231 is most likely to provide the informati on needed by EPA for making a registration 3232 decision. . 3233 The Harmonized Guidelines are guidanc e. The guidelines themselves do 3234 not impose mandatory requirem ents. Applicants are not r equired to submit studies 3235 developed according to the guidelines to fulfill a data requirement. However, EPA 3236 encourages applicants to use the guidelines . These guidelines were developed to 3237 provide applicants, who would be c onducting the studies, with recognized 3238 approaches for developing high quality data, guidance on evaluating and reporting 3239*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 140 of 234 data, definition of terms, and suggested study protocols. It would not be possible 3240 to address every conceivable circumst ance that could occur when conducting a 3241 particular study. Instead the guidelines provide a framewor k that provides 3242 recommended approaches for conducting studi es while offering flexibility and 3243 accommodation for individual circum stances where appropriate. EPA has 3244 reviewed and accepted many studies, on a case-by-case basis, that were not 3245 conducted in accordance with current gui delines, but which provided suitable 3246 information for risk assessment purposes. 3247 Since guidelines cannot account fo r every conceivable circumstance, EPA, 3248 for certain studies, proposed a “required” or “highly suggested” protocol 3249 submission and review step in the test notes to the tables in the proposed rule. 3250 Generally, these pertain to those studi es that are “newer” or have not been 3251 routinely conducted. Gi ven that the applicant co mmunity and contracting 3252 laboratories would have less experience in conducting these kinds of “newer” 3253 studies, protocol submission, review, and meetings about proposed protocols are 3254 beneficial to both the applicant and EPA, and help assure t hat the study submitted 3255 for review should provide the informa tion needed by EPA for its registration 3256 decision. 3257 EPA acknowledges that in some instanc es there are: Data requirements 3258 for which guidelines are not available; outdated guidelines that need revision; and 3259 draft guidelines that need to be finalized. Ideally, up-to-date final guidelines would 3260 be available for every dat a requirement. Up-to-date guidelines increase the 3261 possibility that EPA will receive useful data and that applicants can produce such 3262*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 141 of 234 data in the most cost-efficient and consiste nt manner. However, given the rapidly 3263 evolving scientific methods for conducti ng toxicity, exposure, and ecological 3264 studies with pesticides, study guideli nes often need frequent updating to include 3265 the latest techniques and methods. Moreover, the need for openness and 3266 transparency means that developing a gui deline or updating an existing one can 3267 be a lengthy process. In a recent letter to CropLife America (June 26, 2009), 3268 (Ref. 11) the Agency discuss ed the timeframe for developing the Terrestrial Field 3269 Dissipation Guideline (835.6100), which sp anned 15 years. During that time 3270 period, there were presentations to t he SAP, at various symposia including ones 3271 conducted by the American Chemical Society and the American Society of 3272 Agronomy, and to a workshop in Washington, DC co-hosted by EPA and 3273 Canada’s Pest Management Regulatory Agency. 3274 Thus, the reality is that test guidelines will always be a work in progress. At 3275 the same time, EPA is implementing a regulatory program under FIFRA and 3276 FFDCA section 408 under which it must make timely decisions on the safety of 3277 pesticide products based on toxicity and exposure testing. Guidance on optimal 3278 testing procedures remains an Agency goal but the absence of testing guidelines 3279 is not a barrier to the imposition of te sting requirements necessary to make the 3280 required statutory findings. 3281 In 2008, OMB, during its Executive Order 12866 review of the proposed 3282 rule, recommended that certain draft guidel ines be finalized before publishing the 3283 Antimicrobial Data Requirements fi nal rule. These guidelines were: 3284

 Applicator product use information (OPPTS 875.1700) 3285*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 142 of 234  Post application product use information (OPPTS 875.2700). 3286

 Indoor surface residue dissipation (OPPTS 875.2300). 3287

 Non-dietary inges tion (OPPTS 875.3000). 3288 In the proposed rule (October 8, 2008; 73 FR 59382), EPA discussed that 3289 the publicly-available versions of these guidelines were only available on the SAP 3290 portion of EPA’s website (73 FR 59399 – 59401). EPA intends to finalize these 3291 guidelines in the near future. Also, as previously discussed, the data requirement 3292 referencing the non-dietary ingestion guide line was removed from the final Post3293 Applicator Exposure Table in § 158.2270. (see Unit XIII.D). 3294 EPA acknowledges that the guidelines for dermal and inhalation exposure 3295 studies need revisions to account for new advances in how exposure is measured 3296 and modeled. To provide needed informa tion to the public and applicants, EPA 3297 will change the way these guidelines are referenced on the Harmonized 3298 Guidelines website by adding links to the SAP and Human Studies Review Board 3299 (HSRB) meetings at which the changes needed to conduct one of these studies 3300 were publicly discussed. 3301 Since the publication of the propos ed rule on October 8, 2008, EPA has 3302 worked to update and finalize a number of guidelines. On April 15, 2009, EPA 3303 published in the Federal Register (74 FR 17479) a Notice of Availability 3304 describing updates to 16 environmental fa te guidelines. On January 27, 2010, (75 3305 FR 4380) EPA published four draft product performance guidelines for comment. 3306 These four guidelines (810.2000, 810. 2100, 810.2200, and 810.2300) were 3307 developed over an extended peri od of time with multiple levels of review across 3308*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 143 of 234 divisions and program offices in EPA, ex pert external peer review by the FIFRA 3309 Scientific Advisory Panel, and discussi ons with and comments from the regulated 3310 community. Many of the technical changes described in these four draft 3311 guidelines have been in use by the Agency for several years. Three additional 3312 product performance guidelines (810. 2400, 810.2500, and 810.2600) should be 3313 published for comment in a timeframe similar to that of publicati on of the final rule 3314 for Antimicrobial Data Requir ements. Similarly, the nontarget organism and plant 3315 protection guidelines are expected to be finalized by the end of 2011. 3316 Before finalizing a guideline, EPA pr ovides many opportunities for public 3317 comment. EPA’s commitment to transpar ency is not new. Transparency allows 3318 all stakeholders to know what, how, and wh y EPA is adopting a guideline. EPA’s 3319 procedures for developing a guideline is descri bed in a Notice of Availability that 3320 published on August 28, 1996 (61 FR 44308): 3321

 Guidelines under development (whet her new or being substantially 3322 revised) are made available for public comment. 3323

 Guidelines under development (whet her new or being substantially 3324 revised) undergo an external peer review process. Most commonly, the peer 3325 review process would be a re view by the FIFRA SAP. 3326

 Reformatted guidelines (no substant ial revisions) are not subject to 3327 review and comment. 3328

 Public review and comment is also used when EPA guidelines are 3329 being harmonized with OECD guidelines. 3330 B. Harmonization of Guidelines with OECD 3331*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 144 of 234 1. Comment. EPA should harmonize its guidel ines with those of OECD. 3332 2. EPA’s Response . EPA agrees with this comment and is continuing to 3333 harmonize guidelines, to the extent practic able, as they are revised. As noted on 3334 its website http://www.epa.gov/pesticides/science/guidelines.htm , EPA has 3335 several harmonization activities underway with the OECD. The Master List of 3336 Harmonized Test Guidelines includes a reference to an OECD guideline, once 3337 harmonized. All harmoni zed OECD test guidelines 3338 ( http://www.epa.gov/epahome/exitepa.htm ) fall under the OECD Mutual 3339 Acceptance of Data decision, which calls for acceptance for regulatory use by all 3340 OECD member nations. Additionally, unde r 40 CFR 158.70(d)(2), acceptance of 3341 testing conducted in accordance wit h OECD protocols is described. 3342 Harmonized test guidelines reduce the burden on chemical producers and 3343 conserve scientific resources, including t he minimal use of laboratory test animals. 3344 They also form a basis for work sharing and cooperat ion among all OECD 3345 countries. U.S. experts are engaged in har monization activities through OECD to 3346 revise toxicology and ecotoxicology te st guidelines. These revisions will 3347 emphasize reduction, refinement, or repl acement of animal testing, while 3348 incorporating the latest advances in sci ence. Animal welfare concerns and 3349 international regulatory needs are being considered in the course of these 3350 revisions of the test guidelines. In addi tion, EPA is actively engaged in OECD’s 3351 development and harmonization efforts for guidelines to address environmental 3352 fate, endocrine disruptor screening, and effi cacy of antimicrobial pesticides. 3353*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 145 of 234 Tests conducted in accordance with the requirements and 3354 recommendations of the applicable OECD pr otocols can be used to develop data 3355 necessary to fulfill the data requirem ents. However, some of the OECD 3356 recommended test standards, such as test dur ation and selection of test species, 3357 are less restrictive than those re commended by EPA. When using OECD 3358 protocols, applicants should be careful to observe the test standards so that the 3359 data generated will satisfy the EP A data requirements. 3360 C. Guidelines Specific to Antimicrobials 3361 1. Comment . The commenter claimed that guidelines specific to 3362 antimicrobials are needed. 3363 2. EPA’s Response . EPA agrees that for certai n scientific disciplines or 3364 certain studies that antimicrobial-s pecific guidance may be needed. The data 3365 required to demonstrate product performance would be very different for an insect 3366 repellent or a termiticide versus that needed for sanitizers and disinfectants. 3367 Exposure studies could be conducted differe ntly for an antimicrobial used in a 3368 food-processing plant versus a conventi onal pesticide sprayed on an agricultural 3369 field. Exposure studies could also be conducted via the same method: A spray 3370 can with an insecticide is assessed using the same techniques as a spray can 3371 with a disinfectant with any differences in the assessment being attributed to 3372 actual use conditions, such as, indoors versus outdoors or surfaces sprayed. For 3373 other scientific disciplines such as toxi cology or product chemistry, generally, with 3374 a few exceptions, the gui dance would be the same : A carcinogenicity, 3375 developmental, or reproductive toxicity study would be conducted similarly for an 3376*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 146 of 234 antimicrobial or a conventi onal pesticide. However, as noted in Unit X.F, the 3377 Ames assay may not be useful for a ssessment of mutagenic potential of 3378 antimicrobial pesticides. 3379 XIX. Discussion of Key Comments on Endangered Species Assessments 3380 A. Endangered Species Assessment for Antimicrobials 3381 1. Comment. The commenter argued that EPA needs to recognize the 3382 manner in which antimicrobials may re sult in environmental exposure and the 3383 regulations under statutes ot her than FIFRA in order to promote an effective and 3384 efficient approach to regulating antimicrobi al pesticides with regard to endangered 3385 and threatened species. According to t he commenter, antimicrobials are not 3386 applied directly to the environment, but environmental exposures from 3387 antimicrobial pesticides result from point -source discharges or slow release from 3388 pesticide-containing materials. 3389 2. EPA’s Response . EPA agrees that there are differences between 3390 antimicrobial pesticides and agricultural pesticides. As discussed in the proposed 3391 rule (October 8, 2008; 73 FR 59425), for agricultural pesticides, there is generally 3392 greater specificity relative to wher e a pesticide may be used compared to 3393 antimicrobial pesticides. Agricultural pesti cides are typically used on crops. As 3394 part of its endangered and threatened species assessment, EPA extracts 3395 information on county-level crop occurrence and acreage within counties of particular 3396 crops from the most recent U.S. Department of Agriculture’s National Agricultural 3397 Statistics Services’ Census of Agriculture. Because antimicrobial pesticides are 3398 typically not applied directly to the environment, it is easier to delineate and overlay 3399 agricultural pesticide use with endangered or threatened species locations than to 3400*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 147 of 234 delineate and overlay antimicrobial pesticides use. Nevertheless, wood 3401 preservatives, antifoulant paints and c oatings, and other antimicrobial uses, 3402 including uses in swimming pool water, i ndustrial slimicides used in recirculating 3403 water cooling towers, and paper mills, have the potential for environmental 3404 exposures. The Agency is working to refine its endangered species assessment 3405 for antimicrobial pesticides to account for the unique mechanisms involved in 3406 application and use of antimic robial pesticides, and the different routes through 3407 which antimicrobial pestici des enter the environment. 3408 EPA recognizes that antimicrobials, like any other pesticide product, may 3409 be subject to other Federal, State and loca l laws. FIFRA requires that, before a 3410 pesticide may be lawfully sold or distribut ed in the United Stat es, the product must 3411 be registered by EPA, unless the produc t is exempt from registration 3412 requirements. Prior to r egistering a pesticide product, EPA must first ensure that 3413 the pesticide, when used according to label directions, can be used without posing 3414 unreasonable risks to humans and the environment. The registration of a 3415 pesticide product, whether it is an antimicrobial or other type of pesticide product, 3416 is considered an “action” subject to the Endangered Species Act (ESA). The ESA 3417 requires all Federal agencies to ensure t hat any action they permit or authorize 3418 will not result in likely jeopardy to the continued existence of endangered or 3419 threatened species, or destroy or adverse ly modify habitat designated as critical 3420 by the U.S. Fish and Wildlife Service (F WS) or National Marine Fisheries Service 3421 (NMFS). 3422*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 148 of 234 In order to ensure EPA’ s actions are consistent with the ESA, the Agency 3423 must assess the potential for both direct and indirect effects to any potentially 3424 exposed threatened or endangered specie s and critical habitat, independent of 3425 whether exposure results from a point-source discharge or the slow release of a 3426 pesticide containing material. If effects may occur, EPA consults with the FWS or 3427 NMFS to determine whether there may be jeopardy to the species or destruction 3428 or adverse modification to habitat designated as critical. 3429 B. Method for Conducting Endangered Species Assessments 3430 1. Comment. A commenter claimed that EPA/OPP does not have a 3431 mature program currently in place for antimicrobial environmental risk assessment 3432 generally. More specifically, the comm enter contended that EPA does not have a 3433 program in place for assessing pot ential impacts on endangered and threatened 3434 species relevant to antimicrobials and t heir uses. The comment er argued that until 3435 EPA scientifically substantiates data requirements to use in estimating 3436 antimicrobial environmental exposures and modeling the potent ial for risks from 3437 such exposures, it will not be feasible to make any meaningful determinations on 3438 potential impacts to endangered species. The commenter concluded that it is 3439 thus premature for the EPA to determine how it should approach antimicrobials 3440 with regard to endangered species. 3441 2. EPA’s Response . EPA disagrees with the commenter. EPA has a 3442 robust program for completi ng antimicrobial environmental risk assessments, as 3443 outlined in the preamble to the proposed ru le (73 FR 59405). Environmental fate 3444 studies evaluate the mobility, distribution and dissipation of a pes ticide in various 3445*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 149 of 234 compartments of the environment, such as water, soil, air, and sediment. 3446 Ecological effects data are used by t he Agency to determine the toxicological 3447 hazards of pesticides to various nontarget organisms, such as birds, mammals, 3448 fish, bees, terrestrial and aquatic inve rtebrates, and plants. The required 3449 environmental fate studies and ecological effects (both plant and animal) data 3450 provide the foundation for an environmental risk assessment. EPA’s 3451 environmental risk assessment for antimic robials combines environmental fate 3452 studies with ecological effects data to determine the potential of the pesticide to 3453 cause harmful effects to nontarget organi sms and plants. T he data requirements 3454 that will be codified in the final rule will provide sufficient information for EPA to 3455 perform an ecological risk assessment. 3456 EPA/OPP’s process for assessing the potential risks of a pesticide to 3457 federally listed threatened or endangered sp ecies and their designated critical 3458 habitat is described in the document ti tled “Overview of the Ecological Risk 3459 Assessment Process in the Office of Pe sticide Programs, U. S. Environmental 3460 Protection Agency – Endangered and Threatened Species Effects 3461 Determinations” released in January 2004. Appendix A to that document – 3462 “Overview of OPP’s Screening-Level Ec ological Risk Assessment Process for 3463 Antimicrobial Pesticides” – explains both the data needed and the process that 3464 would be used by EPA to assess pot ential risks to endangered and threatened 3465 species from antimicrobial pesticides. 3466 EPA’s assessment of potential impacts on endangered and threatened 3467 species begins with a screening level assessment to determine if there is a 3468*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 150 of 234 potential concern. When the screening-level ecological risk assessment raises 3469 potential concerns related to a listed species, EPA then conducts a species-specific 3470 evaluation to refine the assessment. The more refined assessment should involve 3471 clear delineation of the action area associated with the proposed use of the 3472 pesticide and best available information on the temporal and spat ial co-location of 3473 the listed species with respect to t he action area. EPA not es that with the 3474 publication of the proposed rule, the discu ssion in Appendix A is out of date. In 3475 response to comments received on the pr oposed antimicrobial data requirements, 3476 EPA indicated it is no longer relying on its proposed approach classifying use 3477 patterns as high/low or minimal/significant exposure uses with regard to ecological 3478 effects testing. However, the Ag ency’s basic approach to endangered species 3479 risk assessments, which combine environment al fate studies with ecological 3480 effects data to determine the potential of t he pesticide to cause harmful effects to 3481 endangered species, has not changed. In addition, the Agency will conduct an 3482 assessment for antimicrobial pesticides with down-the-drain uses, as described in 3483 response to comment 134.1 in the Response to Comments Document in the 3484 docket at http://www.regulations.gov . The codified data requirements and the 3485 down-the-drain assessment will extend A D’s ability to understand the potential 3486 impacts of antimicrobial pesticides on endangered species. 3487 EPA cannot wait to comply with the ESA until newer, more advanced, 3488 models are available or additional data needs are determined: Federal agencies 3489 must comply with the ESA by performi ng their assessments and analyses using 3490 the best scientific and commercial data ava ilable. As a part of Registration 3491 Review, EPA is conducting species-specif ic environmental risk assessments that 3492*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 151 of 234 will allow EPA to determine whether the ant imicrobial pesticide product has “no 3493 effect” or “may affect” federally-lis ted threatened or endangered species (listed 3494 species) or their designated critical habi tats. When an assessment concludes that 3495 a pesticide product’s use “may effect” a lis ted species or its designated critical 3496 habitat, the Agency will consult with the FWS and/or NMFS, as appropriate. 3497 XX. Discussion of Key Comment s on Endocrine Disruption 3498 A. Comment 3499 The commenters noted that EPA did not include any studies to assess 3500 endocrine disruption effects. 3501 B. EPA’s Response 3502 The commenter is correct that EPA did not include within the proposed 3503 subpart W, studies whose so le purpose is to assess endocrine disruption effects 3504 in avian and aquatic species. The Agency is also not including such studies in this 3505 final rule. 3506 With regards to toxicology data r equirements, as required by FIFRA and 3507 FFDCA, EPA reviews a toxicological databa se of numerous studies to assess 3508 potential adverse outcomes from exposure to chemicals. Collectively, these 3509 studies include acute, subchronic and chr onic toxicity, including assessments of 3510 carcinogenicity, neurotoxicity, devel opmental, reproductive, and general or 3511 systemic toxicity. These studies include endpoints which may be susceptible to 3512 endocrine influence, including effects on endocrine target organ histopathology, 3513 organ weights, estrus cyclic ity, sexual maturation, fertility, pregnancy rates, 3514 reproductive loss, and sex ratios in offspring. EPA reviews these data and selects 3515*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 152 of 234 the most sensitive endpoints for relev ant risk assessment scenarios from the 3516 existing toxicological database. 3517 With regards to ecotoxicity data requi rements, as required by FIFRA and 3518 FFDCA, EPA reviews a nontarget organism database of numerous studies to 3519 assess potential adverse outcomes from ex posure to chemicals. For ecological 3520 hazard assessments, EPA evaluates acute tests and chronic studies that assess 3521 growth, developmental and reproductive effe cts in different taxonomic groups. 3522 EPA reviews these data and selects the most sensitive endpoints for relevant risk 3523 assessment scenarios from the exis ting nontarget organism database. 3524 Through a separate effort, the Ag ency has also developed a screening 3525 battery to identify chemicals that ma y have effects on the hormone systems of 3526 humans and wildlife. As required under FFDCA section 408(p), the Agency 3527 developed the Endocrine Disr uptor Screening Program (EDSP) to determine 3528 whether certain substances (including pes ticide active and other ingredients) may 3529 have an effect in humans or wildlife simila r to an effect produced by a “naturally 3530 occurring estrogen, or other such endocri ne effects as the Administrator may 3531 designate.” The EDSP employs a two- tiered approach to making the statutorily 3532 required determinations. Tier 1 consists of a battery of 11 screening assays to 3533 identify the potential of a chemical s ubstance to interact with the estrogen, 3534 androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through 3535 Tier 1 screening and are found to have the pot ential to interact with E, A, or T 3536 hormonal systems will proceed to the nex t stage of the EDSP where EPA will 3537 determine which, if any, of the Tier 2 tests are necessary based on the available 3538*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 153 of 234 data. Tier 2 testing is designed to ident ify any adverse endocrine-related effects 3539 caused by the substance, and establish a dose-response relationship between the 3540 dose and the E, A, or T effect. 3541 Between October 2009 and February 2010, EPA issued test orders/data 3542 call-ins for 58 pesticide active ingredients and nine inert ingredients. This list of 3543 chemicals was selected based on the potential for human exposure through 3544 pathways such as food and water, resident ial activity, and certain post-application 3545 agricultural scenarios. This list should not be construed as a list of known or likely 3546 endocrine disruptors. 3547 Under FFDCA section 408(p) the Agency must screen all pesticide 3548 chemicals, including antimicrobials. A ccordingly, EPA anticipates issuing future 3549 EDSP test orders/data call-ins for a ll pesticide active ingredients. 3550 For further information on the ED SP including the status and test 3551 guidelines, please visit the website: http://www.epa.gov/endo/. 3552 XXI. Discussion of Key Comments on Effective Date 3553 A. Comment 3554 Several commenters have expressed concern over when the final rule 3555 would take effect. One commenter stated that compliance with the Administrative 3556 Procedures Act requires EPA to apply any final rulemaking on data requirements 3557 for antimicrobials only to applications subm itted after the effective date; otherwise, 3558 EPA would be promulgating the final rule retroactively. The commenter also 3559 asserted that EPA should be consistent in its implementation of effective dates, 3560 noting that EPA did not impose new dat a requirements on pending conventional 3561*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 154 of 234 pesticide registrants when the conventiona l pesticide rules were revised. A 3562 second commenter suggested t hat registrations pending at the time of the final 3563 rule publication be given conditional regist ration under section 3(c)(7) of FIFRA or 3564 under 3(c)(5) if the requirement s of part 161 have been met, and that 3565 implementation of the part 158, subpart W da ta requirements occur at the time of 3566 periodic registration review. Another commenter noted that EPA has provided 3567 reasonable notice to registrants and recomm ends that EPA implement the rule as 3568 soon as technically feasible. A different commenter questioned whether 3569 additional Pesticide Registra tion Improvement Act (PRIA) registration fees would 3570 be required for pending applications if the registrant did not meet new data 3571 requirements and withdrew the applicati on, or if the Agency issued a 3572 determination that it cannot grant the application. 3573 B. EPA’s Response 3574 EPA will follow an approach similar to that used for conventional pesticides 3575 following the promulgation of t hat portion of 40 CFR part 158. 3576 As previously discussed, the final rule for antimicrobials contains 11 “new” 3577 data requirements. “New ” means that the data r equirement has never been 3578 required, or has rarely been required on a case-by-case basis and has not been 3579 routinely considered during the Agency’ s evaluation of the data needed for the 3580 purpose of risk assessment. The new dat a requirements being codified include 3581 eight that were proposed and three that have been added based on public 3582 comments received about the proposed rule. 3583*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 155 of 234 EPA recognizes that during early implementation of 40 CFR part 158, 3584 subpart W not all application packages may have all of the newly-required data. 3585 Therefore during early implementation of 40 CFR part 158, subpart W, EPA will 3586 accept for review and eval uation application packages that may not have all of the 3587 newly required data in appropriate case s supported by adequate justification. 3588 This early implementation period could ex tend up to two years post-promulgation 3589 for situations in which a more time-int ensive new study is missing but could be 3590 less for other situations, such as fo r less time-intensive new studies. The 3591 applicant should address the issue of ti ming (i.e., why the data are not yet 3592 submitted and when the data can be subm itted) with respect to any missing 3593 newly-required data, in t heir justification. 3594 EPA is statutorily required to evaluat e the proposed pesticide thoroughly to 3595 ensure that it will not unreasonably harm hu man health or the environment. For 3596 pesticides needing FFDCA section 408 toleranc es, EPA is statutorily required to 3597 make a safety finding that the pesticide c an be used with "reasonable certainty of 3598 no harm." In cases where the applicati on may not have all the required data, EPA 3599 would evaluate whether a r egistration determination or a safety finding can be 3600 made based on the available data or on t he results of other studies in the 3601 pesticide’s database. If there is insuffi cient information, and if the database does 3602 not provide information on the endpoints that would be tested, or data provided by 3603 the applicant or information in the databas e shows evidence of effects, EPA may 3604 not be able to make a registration decision or safety finding. In such cases, the 3605 application may be denied or the applic ant may choose to withdraw the 3606*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 156 of 234 application pending completion of the needed data. In so me cases, conditional 3607 registrations may be appropriate for c onsideration. Among other things, a 3608 determination that the propos ed use will not significantly increase the risk of 3609 unreasonable adverse effects on the envir onment will need to be made. If EPA 3610 can make that determination and the other elements for a conditional registration 3611 are met, then a conditional registra tion may be appropriate and the new data 3612 required as a condition of registration. If there is a basis for granting a conditional 3613 registration, then the ti meframe for conditioning t he registration would be 3614 determined based on factors such as the required studies involved and the length 3615 of time required to conduct those studies. 3616 Importantly, it should be noted that acceptance of an application for 3617 processing during early implementation of 40 CFR part 158, subpa rt W that does 3618 not result in a conditional registrati on does not permanently relieve the applicant 3619 from providing the newly r equired data. Based on the particular case involved, 3620 the Agency will employ appropriate mechanism s, for example, through a DCI or 3621 through the registration review process, to ensure the generation and submission 3622 of any missing newly-required data. 3623 With respect to pending applications that are withdrawn, additional PRIA 3624 registration fees will generally only be requi red if the applicant seeks to pursue the 3625 action again by submitting a new applicat ion (and addressing the deficiencies in 3626 the original application). In withdrawal situations, the Agency provides a refund for 3627 any work that the Agency did not per form on the application following a 3628 withdrawal. Similarly, a determination t hat the application cannot be granted does 3629*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 157 of 234 not require additional PRIA r egistration fees. In that ca se, additional fees will only 3630 be incurred if the application is subs equently withdrawn or denied, and the 3631 applicant seeks to pursue the action agai n and submits a new application. 3632 XXII. Discussion of Key Commen ts on the Economic Analysis 3633 A. Comparing Estimates of Cost of the Proposed Rule 3634 3635 1. Comment. A commenter performed an independent economic analysis 3636 (EA) for the proposed rule. According to the commenter’s analysis, the cost of 3637 proposed part 158, subpart W is greater th an that estimated by the EPA. In 3638 addition, the unit test costs and frequency of tests used in the commenter’s 3639 analysis are different than EPA’s. 3640 2. EPA’s Response . EPA reviewed the commenter’s analysis and based 3641 on that review revised the EA for the final rule. EPA’s evaluation of the 3642 commenter’s EA indicated there were t he following differences between the two 3643 EAs: 3644

 The cost estimates used for the studies 3645

 Overhead costs were included by the commenter, but not by EPA 3646

 Costs for Registration Re view (see Unit XXII.C.) 3647 The differences between the cost of t he proposed rule as estimated by the 3648 commenter and the cost as assessed by the Agency for new registrations are 3649 explained in the following subunits. 3650 i. How data requirement costs are calculated. The annual cost of a data 3651 requirement is the product of three factors: unit test cost, probability of the test 3652 being required, and the number of registrations in the industry per year for the 3653 registration type and use. That is: 3654*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 158 of 234 Industry Cost of a data requirement = Unit test cost x test probability x number of 3655 registrations 3656 These costs are summed for all data require ments, uses, and registration types to 3657 get the total annual cost of the data requirements for the industry. 3658 ii. Differences in unit test costs. EPA acknowledges that there are 3659 significant differences between the Agency’s analysis and the commenter’s 3660 analysis regarding the unit test costs. Acco rding to the commenter’s EA, the costs 3661 were provided to them by their client’s technical consultants, and are “based on 3662 quotes from laboratories, actual expe rience, and professional judgment.” The 3663 commenter did not provide sufficient information with which to evaluate the 3664 commenter’s test cost estima tes. Additionally, EPA notes that having all test cost 3665 estimates ending in zero could be indicative of estimation. 3666 EPA’s unit test costs for each dat a requirement were obtained by 3667 contacting established contract research organizations (CROs) to assess what the 3668 labs would charge to conduct studies acco rding to specific designs provided by 3669 EPA, or as specified in OPPTS guidelines . Upper and lower cost estimates were 3670 requested. For each test, the upper co st estimates from each CRO were 3671 averaged to obtain a high average estimate . A similar calculation was done for 3672 the lower cost estimate. EPA’s estimate is the average of the high and low 3673 average estimates. 3674 iii. Test costs and overhead costs. The commenter added 30 percent to 3675 their test cost estimates to account for the overhead of t he registrants managing 3676 and overseeing the tests they contract to the labs. EPA acknowledges that there 3677*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 159 of 234 are costs other than test costs associat ed with registering and maintaining the 3678 registrations of pesticide products. Overhead is a not new cost, attributable to the 3679 rule, and EPA does not believe that over head costs will change significantly as a 3680 result of codifying data requirements for antimicrobials. EPA does not include 3681 overhead costs in its economic analyses of data requirements rules because the 3682 Agency accounts for other registration cost s such as overhead in the Information 3683 Collection Request (ICR) for FIFRA Sect ion 3 Registration under the Paperwork 3684 Reduction Act. 3685 iv. Test probabilities. EPA’s test probabilities (t he probabilities of tests 3686 being required for a registration actions) were based on a sample of 70 actual 3687 antimicrobial registration actions out of 90 relevant new registration actions during 3688 the six year period beginning 2000 and ending 2005, supplemented with EPA’s 3689 scientific judgment. The time peri od (2000-2005) was chosen for EPA’s EA 3690 because the analysis in the EA was started in 2006. The commenter claims to 3691 have based the test probabilities used to make their estimates on a sample of 29 3692 registration review cases (not new r egistrations) occurring between 2008 and 3693 2010. 3694

v. Factors which drive cost s for new registrations. To determine the 3695 influence of the previously-discussed factors on the difference between the 3696 commenter’s and EPA’s estimates, EPA performed the following analysis on the 3697 data requirements costs and incremental cost s using the same unit test costs and 3698 test probabilities used in the proposed rule: 3699*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 160 of 234  To account for the effect of the uni t test costs on the data requirements 3700 costs and incremental costs, EPA substitu ted the commenter’s unit test costs 3701 without overhead into EPA’s analysis of the proposed rule using EPA’s test 3702 probabilities and number of regi strations. If there were no changes, this would 3703 indicate that the test costs were not driving the differences in estimates. 3704

 To account for the effect of test probabilities and number of 3705 registrations, EPA substituted the commenter ’s unit test costs with overhead into 3706 EPA’s analysis. In this case, t he difference between the EPA’s and the 3707 commenter’s analysis is contained in the test probabilit ies and number of 3708 registrations. If there were no changes, this would indicate that the test 3709 probabilities and number of regi strations were not driving the differences between 3710 the two analyses. Since the commenter includes overhead in their analysis, 3711 overhead was included in this comparison to make other things equal so that the 3712 differences in test probabilities and number of registrations could be isolated. 3713 vi. Results. The results of the factor anal ysis are presented in Table 1. 3714 Table 1: Comparison of Data R equirement Costs and Factors for New 3715 Registrations 3716*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 161 of 234 Column A B C D Unit Test Costs according to: EPA Proposed Rule Commenter without overhead Commenter with 30% overhead Commenter with 30% overhead Test Probabilities according to: EPA EPA EPA Commenter Number of Registrations according to: EPA EPA EPA Commenter

Data Requirement Cost according to Proposed Rule ($ millions) $15.0 $19.9 $25.5 $25.9

Cost of Proposed Rule (Incremental Costs) ($ millions) $3.9 $7.6 $9.8 $9.2
3717 Column A exhibits the data requirem ents and incremental costs from EPA’s 3718 EA of the proposed rule. In column B, the data requirem ents and incremental 3719 costs are calculated using t he commenter’s unit test co sts without overhead costs, 3720 but EPA’s test probabilities and nu mber of registrations. Column C is the same as 3721 column B, but with overhead costs included. Finally, column D exhibits the data 3722 requirements and incremental costs with overhead as calculated by the 3723
commenter. 3724 The result of the first fact or analysis is demonstrated by comparing column 3725 A to column B. In this case, the difference between the two columns is the unit 3726 test costs. Inserting the commenter’s unit test costs, without overhead, into the 3727 cost estimates with EPA’s test probabilitie s and number of registrations leads to 3728 over a 30 percent increase in data requi rements cost and a nearly 100 percent 3729 increase in increm ental costs. 3730*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 162 of 234 The result of the second factor anal ysis is demonstrated by comparing 3731 columns C and D. In this case, the difference between the two columns is in the 3732 test probabilities and number of registrations. While individual test probabilities 3733 may be different in EPA’s and the commenter’s analyses, the overall effect of the 3734 products of test probabilities and number of registrations, when summed with the 3735 unit test costs, including overhead, are similar in both of these analyses. The 3736 resulting differences in data requirem ents cost and incremental costs are less 3737 than 2 percent and about 6 percent, respecti vely. Therefore, EPA concludes that 3738 any differences in test probabilities and number of registrations used as input 3739 parameters in the calculati ons do not have a significant effect on the total data 3740 requirement cost of new registrations. 3741 Comparisons across columns A, B, and C also provide information on the 3742 portion of the cost difference accounted fo r by overhead costs. Columns A, B, 3743 and C compare the cost of data requirements using the unit test cost estimates of 3744 EPA, and those of the commenter wit h and without overhead. The overhead 3745 costs account for more than one-half of the difference in the tota l cost of the data 3746 requirements, but less than 40 percent of the difference in incremental costs (the 3747 incremental cost is the increase co sts between the base line, part 161, and 3748 proposed part 158, subpart W). 3749 From this comparison, EPA makes the following conclusions. First, 3750 differences in test probabilities and number of registrations do not have a 3751 significant impact on the cost of the ru le. Second, even if EPA and the commenter 3752 used the same probabilities and test costs, inclusion of overhead costs by the 3753*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 163 of 234 commenter would result in a 30 percent di fference in costs. Finally, when the 3754 overhead costs are removed from the comm enter’s analysis, differences in unit 3755 test costs between EPA and the commenter account for most of the differences in 3756 the estimates of the cost of the rule for new registrations. 3757 vi. Revised test costs. In light of the result s of the comparison between 3758 EPA’s and the commenter’s EA, EPA sought to verify its unit test cost estimates. 3759 To examine the costs submi tted by ACC, EPA re-surveyed the cost of conducting 3760 studies for 30 data requirements: The criteria for select ing which test’s cost to 3761 update included how the difference in estima tes would impact on the cost of the 3762 rule, the magnitude of the differences in estimates, and the age and source of 3763 EPA’s estimates. EPA’s data gathering methodology is reproducible, and based 3764 on actual data. EPA does not adjust the lab’ s cost estimates, i.e., the costs are 3765 used as obtained from the laboratory. U nder the Information Quality Act (IQA), 3766 EPA must ensure and maximize the quality, objectivity, utility, and integrity of the 3767 data used in its analyses. 3768 The re-surveyed test costs are used in the EA (economic analysis) for the 3769 final rule. EPA is using its cost estimate s because it has revised its most relevant 3770 and oldest unit test cost esti mates. In addition, the co mmenter did not provide a 3771 basis or sufficient explanation that would meet the standards of the IQA to justify 3772 EPA’s accepting the commenter’s costs. For additional information see response 3773 to comment 40.1 in the Response to Co mments Document and the final economic 3774 analysis, both in the docket at http://www.regulations.gov

. 3775 B. Impact on Small Businesses 3776*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 164 of 234 1. Comment . A Commenter claimed that E PA underestimated costs, is not 3777 fully complying with the Regulatory Flex ibility Act (RFA) and the Small Business 3778 Regulatory Enforcement Fairness Act (SBREFA), and must prepare an Initial 3779 Regulatory Flexibility Asse ssment (IRFA). In addition , the commenter argued that 3780 small businesses will be adversely affect ed, that there will be an "increased 3781 disparity between registrant s and a more uneven playing field," and finally, that a 3782 SBREFA analysis should have been conducted. 3783 2. EPA’s Response. EPA acknowledges that the cost of the data 3784 requirements would likely be a larger per centage of a small business’s revenues, 3785 but did not find that the rule would have a significant adverse economic impact on 3786 a substantial number of small firms. 3787 A regulatory flexibility analysis ex amines the type and number of small 3788 entities potentially subject to the rule, recordkeeping and compliance 3789 requirements, and significant regulatory al ternatives, among other things. RFA, 3790 as amended by SBREFA, requires EPA to consider the economic impact of 3791 proposed rules on small entities. RFA r equires EPA to prepare an IRFA for each 3792 proposed rule, when the rule will have a significant economic impact on a 3793 substantial number of small entities. 3794 To comply with RFA, EPA did a re trospective analysis of what the 3795 additional costs would have been on actual new registrations if the proposed rule 3796 had been in effect during 2000-2005. This anal ysis did not indicate a significant 3797 impact on a substantial number of small entities; instead, the analysis indicated 3798 that 5 percent of small firms (25 out of 500) are likely to experience some impact 3799*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 165 of 234 and only 2.8 percent of small firms (14 out of 500) are likely to experience an 3800 economic impact of 3 percent or more of gross sales. Based on this analysis, 3801 EPA certified that the pr oposed rule would not have a significant adverse 3802 economic impact on a substantial number of small firms. As a result, EPA did not 3803 have to conduct an IRFA nor convene a SBREFA Panel for the proposed part 3804 158, subpart W rule. 3805 In the EA for the final rule, EPA re -estimated the SBREFA analysis with 3806 revised unit test costs and chang es in data requirements. 3807

 About 23 small firms (almost 5%) are likely to experience an economic 3808 impact of 3% or more of gross sales, and 3809

 About 26 small firms, (over 5%) are likely to experience an economic 3810 impact of 1% or more of gross sales. 3811 Hence, had these results been estimated at the proposal stage, EPA would still 3812 have concluded that there would not be a significant impact on a substantial 3813 number of small entities. 3814 C. Cost of New Data Requir ements on Registration Review 3815 1. Comment . A commenter stated that EPA has not accurately stated the 3816 potential costs and benefits, as required by Executiv e Order (EO) 12866. In 3817 particular, EPA has not included the impac t of incremental costs of new data 3818 requirements on registration review, or the cost of consultations. The commenter 3819 also claims that under the PRA, EPA should include the paperwork burden costs 3820 of registration review fo r existing registrants. 3821 2. EPA’s Response . EO 12866 requires the Agency to submit to OMB for 3822 review significant regulatory actions . EPA complied with EO 12866 during 2008 3823*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 166 of 234 by submitting drafts of both the economic analysis and the proposed rule to OMB. 3824 The changes that were made to the proposed rule as the result of OMB’s review 3825 were included in the docket for the proposed rule at http://www.regulations.gov

. 3826 The Agency notes that one purpose of soliciting comments on the economic 3827 analysis at the proposal stage is to get input on where the Agency might improve 3828 the economic analysis. 3829 The commenter is not correct in a sserting that EPA did not include the 3830 impact of incremental costs. The A gency has captured t he anticipated costs 3831 necessary for complying with the regulat ions. See the final Economic Analysis 3832 (Ref. 13) in the docket at http://www.regulations.gov for a more detailed 3833 discussion, particularly sections 5.3 and 5.5. 3834 The commenter is correct in that t he costs of fulfilling the 11 “new” data 3835 requirements during registra tion review were not considered in the Agency’s 3836 economic analysis of the proposed part 158, subpart W data r equirements. EPA 3837 agrees with the commenter t hat registrants of existi ng antimicrobial products will 3838 incur costs during registration review . In fact, EPA relied on the 2005 EA 3839 conducted for the Registration Review Ru le. When registration review was 3840 proposed, EPA prepared an economic analysis of that program, which estimated 3841 the cost of data require ments and paperwork burden according to what would 3842 likely be required in registration review for existing registrants. The 2005 3843 registration review EA estimate of data requi rement costs for existing antimicrobial 3844 pesticides was based on what would lik ely be required for a sample of 3845 antimicrobial active ingredi ents. This would have incl uded all tests that would 3846*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 167 of 234 have been required at that time , i.e., those in current pr actice whether or not in 3847 part 158. 3848 However, the proposed part 158, subpar t W included “new” tests, which 3849 were not anticipated when the economic analysis of the registration review 3850 process was completed. In a final econom ic analysis for part 158, subpart W, EPA 3851 addresses the additional registration review costs for these 11 “new” studies, as 3852 well as other changes from the proposed to final rule including changes made as 3853 a result of the comments received. T he incremental impact for Registration 3854 Review is $ 6.8 M. 3855 The commenter is also correct that EPA did not include the cost of 3856 consultation in its economic analysis. Consultations are longstanding, commonly 3857 used, and valuable processes in EPA’s Pesticide Program and are beneficial to 3858 both EPA and the applicants. However, consultations are not mandatory, and 3859 based on comments received EPA has removed all references to consultations 3860 from the final data requirem ents tables. See Unit V.C for additional information on 3861 the use and purpose of consultations. 3862 XXIII. References 3863 As indicated under ADDRESSES , a docket has been established for this 3864 rulemaking under docket ID number EPA-HQ-OPP–2008–0110. The following is 3865 a listing of the documents that are specif ically referenced in this proposed rule. 3866 The docket includes these documents and other information considered by EPA in 3867 developing this rule, including docum ents that are referenced within the 3868 documents that are included in the docket, ev en if the referenced document is not 3869*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 168 of 234 physically located in the docket. For a ssistance in locating documents, please 3870 consult the technical contact listed under FOR FURTHER INFORMATION 3871 CONTACT

. 3872 Ref. 1: Rule Text of “Dat a Requirements for Pesticide R egistration; Final Rule;” 3873 (49 FR 42856). 3874 Ref. 2: ACC Biocides Pane l; “Regulation of Antimicrobi als that are Indirect or 3875 Secondary Direct Food Addi tives;” (February 2, 2006). 3876 Ref. 3: ACC Biocides Panel; “C omments on EPA’s September 17, 1999 3877 Proposed Rule on Registration Requirements for Antimicrobial Pesticide Products 3878 and Other Pesticide Regulat ory Changes for Codification; (January 18, 2000). 3879 Ref. 4: ACC Biocides Panel; Memor andum to Frank Sanders, “EPA’s Current 3880 Interpretation of the Antimicrobial Refo rm Technical Corrections Act and Section 3881 2(bb) of FIFRA is Inconsistent wit h the Statutes;” (August 3, 2000). 3882 Ref. 5: ACC Biocides Panel; “EPA/FDA Ju risdiction for Food Contact Antimicrobials;” 3883 (July 17, 2003). 3884 Ref. 6: Grizzle, Charles L.; representative of Albri ght & Wilson Americas, Inc., 3885 letter to Lynn R. Goldman; (September 11, 1997). 3886 Ref. 7: ChemReg International, L.L.C.; Tiered Testing for Risk Assessment of 3887 Antimicrobial Pesticides; (September 12, 2002). 3888 Ref. 8: Goldberg, Seth; “Section 2(bb) of FIFRA; Dual Jurisdiction Over Food Contact 3889 Antimicrobials; (April 27, 2001). 3890 Ref. 9: ACC Biocides Panel; “Comments on The Preliminary Risk Assessment for 1,4- 3891 Bis(bromoacetoxy)-2-butene (BBAB);” (August 6, 2001). 3892*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 169 of 234 Ref. 10: ACC Biocides; Hasmukh C. Shah letter to Frank T. Sanders; (August 3, 3893 2000). 3894 Ref. 11: Edwards, Deborah; OPP Respons e to CropLife letter of May 29, 2009; 3895 (June 26, 2009). 3896 Ref. 12: Portier; SAP Waiver; (April 4, 2011). 3897 Ref. 13: USEPA; Final Economic Analysi s of Changes in Data Requirements for 3898 Antimicrobial Pesticides (update date after OMB review). 3899 XXIV. FIFRA Review Requirements 3900 In accordance with FIFRA section 25(a) , a draft of this final rule was 3901 submitted to the FIFRA Scientific Ad visory Panel (SAP). EPA requested the 3902 FIFRA SAP to waive its review of the fi nal rule based on fact that the SAP, in 3903 2008, had waived review of the proposed rule: The final rule does not contain any 3904 new scientific issues warranting additional review by the SAP. The SAP waived 3905 its review on April 4, 2011, st ating that “[t]he final rule does not contain scientific 3906 issues that the Panel has not pr eviously considered” (Ref. 12). 3907 In accordance with FIFRA section 25(a) , EPA has submitted a draft of the 3908 final rule to the appropriate Congressi onal Committees and the Secretary of the 3909 Department of Agriculture. There we re no comments in response to these 3910 submissions. 3911 In accordance with FIFRA section 21(b) , EPA submitted a draft of the final 3912 rule to the Secretary of Health and Hu man Services (HHS). Their comments on 3913 the draft of the final rule included requests to expand further the discussion on 3914 “the differentiation of authorities of the Food [and] Drug Administration (FDA) and 3915*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 170 of 234 EPA on regulation of antimicrobial pesti cides when present in food,” and also, 3916 various edits were requested by FDA’s Offi ce of General Counsel (OGC). In 3917 response, EPA has expanded the differentiation discussion and made various 3918 edits. Both EPA’s OGC and FDA’s OGC vetted the changes. 3919 HHS also requested that EPA further clarify the “guidance for product 3920 registrants in using emerging alternate test methods in evaluation of toxicity.” 3921 EPA agrees that because the science is changing rapidly, continuous 3922 communication with stakeholders will be impo rtant to their understanding of the 3923 availability of alternate test methods t hat OPP would consider . OPP established 3924 the PPDC workgroup on 21st Century Toxicol ogy to support this communication. 3925 Information on OPP's transition to alte rnate methods is available on EPA's 3926 website on OPP’s 21st Century toxicolo gy vision and strategy webpage, which 3927 contains a tools matrix that describes pl ans to incorporate new scientific tools. 3928 FDA also noted that “the data requi rements do not appear to consider 3929 impacts of the proposed pesticide use on ant imicrobial resistance development.” 3930 As discussed in the proposed rule, EPA is a participant on the Interagency Task 3931 force on Antimicrobial Resistance. While the focus of this group is on the use of 3932 antibiotics, the Antimicrobials Division (A D) has participated in the taskforce 3933 efforts by providing review and comment on documents related to antimicrobial 3934 resistance, specifically, t he reports of the Codex Ad Hoc Intergovernmental Task 3935 Force on Antimicrobial Resistance, i ssued through the Codex Alimentarius 3936 Commission. AD also conducted a literature search into the use of antimicrobial 3937 pesticides and the development of resistant bac teria. While this literature search 3938*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 171 of 234 is several years old, AD does not belie ve that there have been substantial 3939 changes since the search was conducted. 3940 The results of the literat ure search did not support a finding that the use of 3941 antimicrobial pesticides leads to devel opment of resistant bacteria. EPA does 3942 consider the impacts of a pesticide's use on the development of antimicrobial 3943 resistance. However, EPA is unaware of a data requirement approach that would 3944 fit this circumstance. Antimicrobial re sistance develops in the environment during 3945 use, or as a result of the use when the micro-organisms that are still present 3946 "swap their genetic material." The effi cacy studies requir ed as part of the 3947 application submission provide informa tion on the product's ability to kill or 3948 deactivate the micro-organism when used according to the directions on the 3949 product. Historically, the concentration of th e antimicrobial in the product is set 3950 well-over the minimum inhibi tory concentration, to assu re that the micro-organism 3951 is killed or deactivated. If information indicated that an antimicrobial product was 3952 not performing effectively, then it is lik ely that the manufacturer would request an 3953 amendment to their registrati on to increase the concentrati on of the antimicrobial 3954 in the product. EPA has been unable to det ermine to what extent there is a 3955 problem of antimicrobial resi stance or what data submitte d as part of a registration 3956 package could predict the env ironmental conditions for developing resistance in 3957 the future. EPA therefore watches, monitors, and mitigates, as needed. 3958 XXV. Statutory and Executive Order Reviews 3959 A. Regulatory Planning and Review 3960*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 172 of 234 Under Executive Order 12866, entitled Regulatory Planning and Review 3961 (58 FR 51735; October 4, 1993), this action is a “significant regulatory action” 3962 because this action might raise novel legal or policy issues arising out of legal 3963 mandates, the President’s priorities, or t he principles set forth in the Executive 3964 Order. Accordingly, EPA submitted this action to the Office of Management and 3965 Budget (OMB) for review under Exec utive Orders 12866 and 13563, entitled 3966 Improving Regulation and Regulatory Review (76 FR 3821; January 21, 2011). 3967 Any changes made in response to OMB recommendations have been 3968 documented in the docket for this action. 3969 EPA has prepared an EA of the potential costs associated with this action, 3970 entitled “Final Economic Analysis of Changes in Data Requirements for 3971 Antimicrobial Pesticides” (Ref. 13), a copy of which is in the docket at 3972 http://www.regulations.gov . This final EA evaluates the potential benefits and 3973 costs expected as a result of registrati ons and registration reviews. The EA is 3974 briefly summarized here. 3975 In its analysis, the Agency considered the potential, additional costs for the 3976 registration of new antimicrobial pestici des or new uses of currently registered 3977 antimicrobial pesticides, as well as the potential, additional costs incurred during 3978 the registration review of exis ting antimicrobial pesticides. 3979 Based on comments received during the public comment period, the 3980 following changes were made to the rulemaki ng, and are therefore reflected in the 3981 final EA: 3982*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 173 of 234  One proposed data requirement will not be codified: Non-dietary 3983 ingestion exposure. The test cost is $75,000. In the proposed rule, EPA 3984 expected to receive the test 0.8 times per year, representing an annual industry 3985 savings of $63, 125. 3986

 EPA revised certain of the data require ments from “NR” or “CR” to “R,” 3987 or vice-versa. 3988

 Based on comments received, three new data requirements were 3989 added: Simulation test to assess the bi odegradability of chemic als discharged in 3990 wastewater, simulation test – aerobic se wage treatment: acti vated sludge units, 3991 and nature of the residue on surfaces. T he rationale for these three new studies 3992 is described in Unit III.D. 3993 The estimated costs for both regist ration review and for a registration 3994 action for the three newly-requi red data requirements are: 3995 1

. Simulation tests to assess the bi odegradability of chemicals in 3996 discharged wastewater and simulation test – aerobic sewage treatment: activated 3997 sludge units . Both of these studies are us ed as part of the down-the-drain 3998 analysis for antimicrobials. The studies are conditionally required for all use 3999 patterns, except for the aquatic areas us e pattern, for which the study is not 4000 required. EPA does not have an estimate for the cost of either of these studies; 4001 instead, for the EA, EPA used the value $33, 000, which is the cost of the porous 4002 pot test. The Agency expect s, however, that the cost of the simulation tests will 4003 be less than this amount. For registrati on review, EPA expects to receive the 4004 porous pot test or one of the simulation tests up to 8.5 time s per year, for an 4005*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 174 of 234 annual industry cost of $280,500. For new registrations, EPA expects to receive 4006 either of the studies up to 7.5 times per year, for an annual industry cost of 4007 $247,500. The total annual cost is $528,000. 4008 2

. Nature of residue on surfaces . This test is part of the residue chemistry 4009 data requirements, and is c onditionally required for all us e pattern categories. The 4010 test cost is $95,000. For registration revi ew, EPA expects to receive this test 1.3 4011 times per year, for an annual industry co st of $118,750. For new registrations, 4012 EPA expects to receive this test up to 0. 5 times per year, for an annual industry 4013 cost of $44,333. The total annual cost is $163,083. 4014 Many test notes for data require ments were revised based on comments 4015 received. Data requirements for certain use patterns were changed from “NR” or 4016 “CR” to “R,” while others were changed from “R” to “CR.” Because the cost of the 4017 rule depends, in part, on the probabilities of the tests being required, these 4018 revisions have resulted in a modification of the cost of the rule. Instead of 4019 estimating the cost of each change indi vidually, the Agency re-estimated the 4020 potential cost of the regul ation as a whole, taking into account the changes 4021 discussed above. 4022 Based on comments received, EPA has updated the unit test costs for 30 4023 selected tests. The criteria for selecti ng which test’s cost to update included: 4024

 How changing the cost estimates woul d impact on the cost of the rule, 4025

 The magnitude of the difference bet ween EPA’s cost estimate and the 4026 commenters’ cost estimate, and 4027

 The length of time since EPA’s cost estimate was last updated. 4028*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 175 of 234 EPA estimated the annual cost of regist ering a new antimicrobial pesticide 4029 or new use of currently-r egistered antimicrobial pesticides, taking into account 4030 both the changes in data requirements and in unit test costs. Both the total 4031 annual industry costs and the newly-imposed costs were estimated. The updated 4032 test costs plus exposure and other test costs revisions since the proposed rule 4033 increased the cost of the rule by about 23 percent compared to the proposed rule. 4034 The estimated total annual industry costs of the final rule is expected to be about 4035 $19.3 million, which is approximately 29 per cent higher than the cost of the 4036 proposed rule. The difference between the baseline costs (the existing data 4037 requirements that were codified in 1984) and the cost of the Agency’s current 4038 practices is about $1 million annually. T he difference between the baseline costs 4039 and the final rule costs, i.e., the increm ental costs is appr oximately $8.2 million 4040 annually. Under the final rule , the average cost per registration action of a new 4041 antimicrobial active ingredient is appr oximately $1 million to $5 million. 4042 For existing chemicals, data requ irements in part 158 subpart W are 4043 relevant to the registration review program which began to replace the 4044 reregistration program in 2006 as a means of systematically reevaluating existing 4045 registrations against the standards of FIFRA. 4046 EPA has evaluated the impact of t he data requirements being codified 4047 today on registrants of existing chemic als undergoing registration review whose 4048 active ingredient databases do not contai n all of the new data requirements. The 4049 average additional cost of registration re view as a result of the new data 4050 requirements is estimated to be about $588,000 for wood preservatives, $284,000 4051*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 176 of 234 for food and indirect food uses, and $260,000 for all other uses. For registration 4052 review, the total annual cost is $6.8 million. 4053 As required, EPA conducted an analysis of the impact of this final rule on 4054 small businesses, as discuss ed in the Unit XXV.C. 4055 B. Paperwork Burdens 4056 The information collection requirements contained in this rule have been 4057 submitted for approval to OMB under the Paperwork Reduction Act (PRA), 44 4058 U.S.C. 3501 et seq . At the time of the proposed rule, EPA prepared a supporting 4059 statement for amending an I CR), entitled “Data Require ments for Antimicrobial 4060 Pesticides (Proposed Rule)” and identifie d by EPA ICR No. 2318.01, a copy of 4061 which is in the docket at http://www.regulations.gov

. 4062 Under PRA, “burden” means the total time, effort, or financial resources 4063 expended by persons to generate, mainta in, retain, or disclose or provide 4064 information to or for a Federal agency. 4065 The information collection activities re lated to the submission of data to 4066 EPA in order to register, amend or retain a new or existing pesticide product or 4067 obtain a tolerance for that product are al ready approved by OMB under PRA. As 4068 such, the supporting statement only addr esses the proposed changes to the data 4069 requirements that impact the informati on collection activities related to 4070 antimicrobial pesticides. The procedures for submitting data to EPA under FIFRA 4071 and FFDCA are not changed in this propos al, and are already approved by OMB 4072 in the following ICRs: 4073*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 177 of 234  Tolerance ICR. Data Submission Activities Associated with 4074 Tolerance Actions (currently approv ed under OMB Control No. 2070-0024 (EPA 4075 ICR No. 0597)); 4076

 Registration ICR. Data Submission Activities Associated with the 4077 Application for a New or Amended Registrati on of a Pesticide (currently approved 4078 under OMB Control No. 2070-0060 (EPA ICR No. 0277)); and 4079

 Reregistration, Special and Registration Review ICR. Data 4080 Submission Activities Associated with t he Generation of Data for Special Review 4081 or Registration Review (currently approved under OMB Control No. 2070-0174 4082 (EPA ICR No. 2288)). 4083 These three program activities ar e an integral part of the Agency’s 4084 pesticide program, including antimicrobial pesticides, and the corresponding ICRs 4085 are regularly renewed every 3 years as r equired by PRA. The total estimated 4086 average annual public repor ting burden currently approved by OMB for these 4087 various activities range from 8 hours to approximately 3,000 hours per 4088 respondent, depending on the activity and other factors surrounding the particular 4089 pesticide product. 4090 In the supporting statement the Agency estimates that the typical, current 4091 annual paperwork burden for regi strants per antimicrobial pesticide registration is 4092 194 burden hours and $12,631. The total annual registrant paperwork burden 4093 and costs for data submission activities for antimicrobial pesticides applicants and 4094 registrants will be upd ated accordingly in the ICRs specified above during the 4095 next, appropriate ICR renewal cycle. 4096*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 178 of 234 An agency may not conduct or sponsor , and a person is not required to 4097 respond to an information collection request unless it displays a currently valid 4098 OMB control number, or is ot herwise required to submit the specific information by 4099 a statute. The OMB control numbers for EPA’s regulations codified in Title 40 of 4100 the Code of Federal Regulations, after appear ing in the preamble of the final rule, 4101 are further displayed eit her by publication in the Federal Register or by other 4102 appropriate means, such as on the relat ed collection instrument or form, if 4103 applicable. The display of OMB control numbers for certain EPA regulations is 4104 consolidated in a list at 40 CFR 9.1. 4105 C. Small Entity Impacts 4106 The Regulatory Flexibility Act genera lly requires an Agency to prepare a 4107 regulatory flexibility analysis of any rule subject to notice and comment rulemaking 4108 requirements under the Administrative Pr ocedure Act or any other statute unless 4109 the agency certifies that the rule will not have a signifi cant economic impact on a 4110 substantial number of small entities. Small entities incl ude small businesses, small 4111 organizations and small governmental jurisdictions. 4112 For purposes of assessing the impacts of today's rule on small entities, 4113 small entity is defined as: (1) a small bus iness as defined by the Small Business 4114 Administration’s (SBA) regulations at 13 CFR 121.201, which is based on either 4115 the maximum number of employees or on the sales for small businesses in each 4116 industry sector, as defined by a 6-digit NA ICS code, and for this rule is a producer 4117 of pesticide products (NAICS 32532), antifoulants (NAICS 32551), antimicrobial 4118 pesticides (NAICS 32561) or wood pres ervatives (NAICS 32519), importers of 4119*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 179 of 234 such products, or any pers on or company who seeks to register an antimicrobial, 4120 antifoulant coating, ballast water treatment, or wood preservative pesticide or to 4121 obtain a tolerance for such a pesticide; (2) a small governmental jurisdiction that is 4122 a government of a city, county, town, school district or special district with a 4123 population of less than 50,000; or (3) a small organization t hat is any not-for-profit 4124 enterprise which is independently owned an d operated and is not dominant in its 4125 field. 4126 After considering the economic impacts of this final rule on small entities, I 4127 certify that this action will not have a significant adverse economic impact on a 4128 substantial number of sm all entities. The factual basis for the Agency’s 4129 determination is presented in the small entity impact analysis prepared as part of 4130 the Economic Analysis for this final rule (R ef. 13), which is available in the docket 4131
at http://www.regulations.gov . EPA has determined that this rulemaking does not 4132 impact any small governmental jurisdiction s or any small non-for-profit enterprise 4133 because these entities are rarely pesticide applicants or regist rants. As such, 4134 EPA has assessed the impacts on small busi nesses. Some of the small entities 4135 directly regulated by this rulemaking are in the pesticide and other agricultural 4136 chemical manufacturing industry sector (N AICS code 325320). Firms in this sector 4137 are considered small under the SBA definition if they employ 500 or fewer people. 4138 The economic analysis for the final rule specifies the NAICS code used for each 4139 of the firms analyzed. 4140 EPA estimates that 750 unique parent companies constitute the total 4141 universe of pesticide antimicrobial regi strants. Of these, based on the SBA 4142*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 180 of 234 definition of a small business and the av ailable sales data for these firms, EPA 4143 estimates that 500, or approximately 67 percent, qualify as a small business. 4144 When considering both registration review and new registrations, on average 4145 each year about 30 small businesses woul d have incurred additional costs under 4146 this rule. EPA estimates that: 4147 C. About 23 small firms (almost 5 percent ) subject to this regulation are likely 4148 to experience an economic impact of 3 per cent or more of gross sales, 4149

 About 3 small firms (0.6 percent) subj ect to this regulation are likely to 4150 experience an economic impact of greater than 1 percent but less than 3 percent 4151 of sales revenues, and 4152

 About 3 small firms (0.6 percent) subj ect to this regulation are likely to 4153 experience an economic impact of greater than 0 percent, but less than 1 percent 4154 of sales revenues. 4155 In addition, there are also opportuniti es for small entities to lower their 4156 potential costs. The propos ed data requirements in many instances are tiered, 4157 with higher-tiered testing triggered on the results of lower-tiered testing. EPA 4158 encourages registrants to consult with the Agency to ensure that only the required 4159 data is submitted. If av ailable, open liter ature or the same tests on similar 4160 products, or alternative means to meet data requirements, such as QSAR, can be 4161 submitted for Agency consideration. Some firms may have surrogate data or they 4162 may share the cost of generat ing data. These may pres ent opportunities for cost 4163 savings by small entities, and all other applicants as well, while allowing the 4164*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 181 of 234 Agency to fulfill its role of making pesti cide regulatory decisions that protect the 4165 general population, sensitive s ub-populations, and the environment. 4166 This rule was proposed on October 8, 2008. Small entities were able to 4167 provide comments during the 90 day public comment period, which was extended 4168 an additional 90 days at the request of st akeholders. On November 6, 2008, EPA 4169 convened a public workshop to explain t he provisions of the proposed rule, 4170 arranging for the workshop to be webcast for those who could not attend the 4171 public workshop in person. 4172 D. Unfunded Mandates 4173 Under Title II of the Unfunded M andates Reform Act of 1995 (UMRA) (2 4174 U.S.C. 1531-1538), EPA has determined that th is final rule does not contain a 4175 Federal mandate that may result in expendi tures of $100 million or more for State, 4176 local, and tribal governments, in the aggregate, or the private se ctor in any one 4177 year. As described in Unit XXV.A, the in cremental costs for this final rule is 4178 estimated at approximately $8.3 million (for registrati on actions) and $6.8 million 4179 (for registration review) per year for the private sect or, which is below the $100 4180 million threshold. Since State, local, and tribal governments are rarely pesticide 4181 applicants, this rule is not expected to significantly or uniquely affect small 4182 governments. Accordingly, this rule is not subject to the requirements of sections 4183 202 and 205 of UMRA. 4184 This rule is also not subject to th e requirements of section 203 of UMRA 4185 because it contains no regul atory requirements that might significantly or uniquely 4186*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 182 of 234 affect small governments. As stated above, State, local, and tribal governments 4187 are rarely pesticide applicants. 4188 E. Federalism 4189 This action does not have federalism implications, because it will not have 4190 substantial direct effects on the States, on the relationship between the national 4191 government and the States, or on the dist ribution of power and responsibilities 4192 among the various levels of government, as specified in Ex ecutive Order 13132 4193 (64 FR 43255; August 10, 1999)

. Since States or local governments are rarely 4194 pesticide applicants or registr ants, this final rule would seldom affect a State or 4195 local government. Thus, Executive Or der 13132 does not apply to this rule. 4196 In the spirit of Executive Order 13132 and consistent with EPA policy to 4197 promote communication between EPA, and State and local governments, EPA 4198 specifically solicited comment on the proposed rule from State and local officials. 4199 EPA did receive comments on substantive parts from local sanitation districts and 4200 associations representing their interest s. Their comments are addressed in the 4201 Response to Comments Document in the docket at http://www.regulations.gov , 4202 and, as appropriate, revisions we re made for the final rule. 4203 F. Indian Tribal Go vernment Implications 4204 This action does not have tribal implic ations, as specified in Executive 4205 Order 13175 (65 FR 67249, November 9, 2000)

. At present, no tribal government 4206 holds, or has applied for, a pesticide regi stration. Thus, Executive Order 13175 4207 does not apply to this action. In the sp irit of the Order, and consistent with EPA 4208 policy to promote communications bet ween the Agency and Indian tribes, EPA 4209*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 183 of 234 specifically solicited comment on the proposed rule from tribal officials. No 4210 comments were received. 4211 G. Protection of Children’s Health 4212 This final rule is not subject to Executive Order 13045, entitled Protection of 4213 Children from Environmental Health Risks and Safety Risks (62 FR 19885, April 4214 23, 1997) because it is not economically si gnificant as defined by Executive Order 4215 12866, and because the Agency does not have reason to believe the 4216 environmental health or safety risks addressed by this action present a 4217 disproportionate risk to children. This rule does not propose an environmental 4218 standard that is intended to have a negativel y disproportionate effect on children. 4219 To the contrary, this rule is intended to provide added protection to children from 4220 antimicrobial pesticide ri sk. EPA will use the data and information obtained by 4221 this action to carry out its mandate under FF DCA to give special attention to the 4222 risks of pesticides to sensitive groups in early lifestages, especially infants and 4223 children. 4224 H. Executive Order 13211: Actions Conc erning Regulations that Significantly 4225 Affect Energy Supply, Distribution, or Use 4226 This final rule is not subject to Executive Order 13211, entitled Actions 4227 Concerning Regulations that Significantly Affect Energy Supply, Distribution, or 4228 Use (6 FR 28355, May 22, 2001) because it is not an economically significant 4229 regulatory action under Exec utive Order 12866, and it is not likely to have any 4230 adverse effect on the supply, di stribution, or use of energy. 4231 I. National Technology Tr ansfer and Advancement Act 4232*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 184 of 234 Section 12(d) of the National Technol ogy Transfer and Advancement Act of 4233 1995 (“NTTAA”), Public Law No. 104-113, 12( d) (15 U.S.C. 272 note) directs EPA 4234 to use voluntary consensus standards in its regulatory activities unless to do so 4235 would be inconsistent with applicable law or otherwise impractical. Voluntary 4236 consensus standards are technical standards (e.g., materials specifications, test 4237 methods, sampling procedures, and business practices) that are developed or 4238 adopted by voluntary consensus standards bodies. NTTAA directs EPA to 4239 provide Congress, through OMB, explanat ions when the Agency decides not to 4240 use available and applicable voluntary cons ensus standards. This action does not 4241 involve technical standards. Therefore, EPA did not consider the use of any 4242 voluntary consensus standards. 4243 J. Environmental Justice 4244
Executive Order 12898 entitled Federal Actions to Address Environmental 4245 Justice in Minority Populations and Low Income Populations (59 FR 7629; 4246 February 16, 1994) establishes federal executive po licy on environmental justice. 4247 Its main provision directs Federal agencies, to the greatest extent practicable and 4248 permitted by law, to make environmental ju stice part of their mission by identifying 4249 and addressing, as appropriate, dispr oportionately high and adverse human 4250 health or environmental effects of their programs, policies, and activities on 4251 minority populations and low-income popul ations in the United States. 4252 EPA has determined that this final rule will not have disproportionately high 4253 and adverse human health or environmental effects on minority or low-income 4254 populations because it increases the leve l of environmental protection for all 4255*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 185 of 234 affected populations without having any disproportionately high and adverse 4256 human health or environmental effects on any population, including any minority 4257 or low-income population. This rule only im pacts entities that intend to register or 4258 currently hold a registration for an antimicrobial pesticide. 4259 XXVI. Congressional Review Act 4260 The Congressional Review Act, 5 U.S.C. 801 et seq ., generally provides 4261 that before a rule may take effect, the A gency promulgating the rule must submit a 4262 rule report to each House of the Congre ss and the Comptroller General of the 4263 United States. EPA will submit a report c ontaining this rule and other required 4264 information to the U.S. Senate, the U. S. House of Representatives, and the 4265 Comptroller General of the United States prior to public ation of the rule in the 4266 Federal Register . This rule is not a “major rule” as defi ned by 5 U.S.C. 804(2). 4267 4268 4269*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 186 of 234 List of Subjects in 40 CFR Part 158 4270 Environmental protection, Admini strative practice and procedure, 4271 Agricultural commodities, Pesticides and pests, Reporting and record keeping 4272 requirements. 4273 List of Subjects in 40 CFR Part 161 4274 Environmental protection, Admini strative practice and procedure, 4275 Agricultural commodities, Pesticides and pests, Reporting and record keeping 4276 requirements. 4277 Dated: ______________ 4278

______________________ 4279 Administrator 4280*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 187 of 234 Therefore, 40 CFR pa rt 158 and part 161 are amended as follows: 4281 4282 1. The authority citation for part 158 continues to read as follows: 4283 Authority: 7 U.S.C. 136-136y and 21 U.S.C. 346a. 4284 2. Revise § 158.1(c)(4) to read as follows: 4285 § 158.1 Purpose and scope. 4286 ***** 4287 (c) *** 4288 (4) Antimicrobial pesticides. Subparts A, B, C, D, and W of this part apply 4289 to antimicrobial pesticides. 4290 3. In § 158.100 revise the heading of paragraph (a); revise paragraph (b); 4291 redesignate paragraph (c) as paragraph (e); and add new paragraphs (c) and (d) 4292 to read as follows: 4293 § 158.100. Pesticide use patterns. 4294 (a). General use patterns for conventi onal, biochemica l, and microbial 4295 pesticides. *** 4296 (b) Pesticide use site index for convent ional, biochemical, and microbial 4297 pesticides. The Pesticide Use Site Index fo r Conventional, Biochemical, and 4298 Microbial Pesticides is a comprehensive li st of specific pesticide use sites. The 4299 index is alphabetized separately by site for all agricultural and all nonagricultural 4300 uses. The Pesticide Use Site Index asso ciates each pesticide use site with one or 4301 more of the 12 general use patterns. It may be used in conjunc tion with the data 4302 tables to determine the applicability of dat a requirements to specific uses. The 4303 Pesticide Use Site Index for Conventiona l, Biochemical, and Microbial Pesticides 4304 will be updated periodically, and is availabl e from the Agency or may be obtained 4305 from the Agency's website at http://www.epa.gov/pesticides

. 4306 (c) Antimicrobial pesticide use patterns. The general use patterns for 4307 antimicrobial pesticides ar e described in § 158.2201. 4308*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 188 of 234 (d) Pesticide use site index for antimicrobial pesticides. The Pesticide Use 4309 Site Index for Antimicrobial Pesticides is a comprehensive list of specific 4310 antimicrobial use sites. The index is al phabetized by antimicr obial use sites, and 4311 associates each antimicrobial use site wit h one or more of the antimicrobial use 4312 patterns. It may be used in conjunction with the data tables to determine the 4313 applicability of data requi rements to specific uses. The Pesticide Use Site Index 4314 for Antimicrobial Pesticides will be updated periodically, and is available from the 4315 Agency or may be obtained from the Agency’s website at 4316 http://www.epa.gov/pesticides

. 4317 (e) *** 4318 §158.400 [Amended] 4319 4. In the table in § 158.400(d) remove t he category “Efficacy of 4320 Antimicrobial Agents,” and all of t he entries under t hat category. 4321 5. Part 158 is amended by revisi ng subpart W to read as follows: 4322 Subpart W--Antimicrobial P esticide Data Requirements 4323 Sec. 4324 §158.2200 Applicability. 4325 §158.2201 Antimicrobial use patterns. 4326 §158.2203 Definitions. 4327 §158.2204 Public health and nonpublic health claims. 4328 §158.2210 Product chemistry. 4329 §158.2220 Product performance. 4330 §158.2230 Toxicology. 4331 §158.2240 Nontarget organisms. 4332*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 189 of 234 §158.2250 Nontarget pl ant protection. 4333 §158.2260 Applicator exposure. 4334 §158.2270 Post-applicat ion exposure. 4335 §158.2280 Environmental fate. 4336 §158.2290 Residue chemistry. 4337 § 158.2200 Applicability. 4338 Part 158, subpart W establishes data requirements for any pesticide 4339 product that is: 4340 (a) A pesticide that is intended for us e as an “antimicrobial pesticide” 4341 within the meaning of FIFRA sec. 2(mm)(1)(A), regardl ess of whether it also 4342 meets the criterion of FIFRA sec. 2(mm)(1)(B). That criterion excludes from the 4343 definition any antimicrobial product that is intended for a food-use requiring a 4344 tolerance or exemption under FFDCA sec. 408 or a food additive regulation or 4345 clearance under FFDCA sec. 409. EPA will apply this subpart to all products 4346 intended for an antimicrobial use, purpose or function; the exclusion in FIFRA sec. 4347 2(mm)(1)(B) does not exclude products fr om the data requirements of this 4348 subpart. 4349 (b) A product that bears both antimic robial and non-antimi crobial uses or 4350 claims. Such a product is subject to the data requirements for pesticides in 4351 subparts C – O, and U or V of this part with respect to its non-antimicrobial uses 4352 and claims, and to the requirements of this subpart W with respect to its 4353 antimicrobial uses and claims. 4354 (c) A wood preservative, including a product that is intended to prevent 4355 wood degradation problems due to fungal rot or decay, sapstain, or molds. 4356*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 190 of 234 (d) An antifoulant, including a produc t that is intended to kill or repel 4357 organisms that can attach to underwater surfaces, such as boat bottoms. 4358 § 158.2201 Antimicrobial use patterns. 4359 (a) Antimicrobial use patterns . The 12 general use patterns used in the 4360 data tables in this subpart are: 4361 (1) Agricultural premises and equipment. 4362 (2) Food-handling/storage establis hments, premises and equipment. 4363 (3) Commercial, institutional a nd industrial premises and equipment. 4364 (4) Residential and public access premises. 4365 (5) Medical premises and equipment. 4366 (6) Human drinking water systems. 4367 (7) Materials preservatives. 4368 (8) Industrial proce sses and water systems. 4369 (9) Antifoulant paints and coatings. 4370 (10) Wood preservatives. 4371 (11) Swimming pools. 4372 (12) Aquatic areas. 4373 (b) Use site index . The Pesticide Use Site Index for Antimicrobial 4374 Pesticides is a comprehensive list of spec ific antimicrobial us e sites. The Index 4375 associates antimicrobial use sites with one or more of the 12 antimicrobial use 4376 patterns. It is to be used in conjunction with the data tables in this subpart to 4377 determine the applicability of data requi rements to specific uses. The 4378 Antimicrobial Pesticide Use Site Index, which will be updat ed periodically, is 4379*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 191 of 234 available from the Agency or may be obt ained from the Agency’s website at 4380 http://www.epa.gov/pesticides. 4381 § 158.2203 Definitions. 4382 Definitions . The following terms are defined for the purposes of this subpart: 4383 Disinfectant means a substance, or mixture of substa nces, that destroys or irreversibly 4384 inactivates bacteria, fungi and viruses, but not necessarily bacterial spores, in the inanimate 4385
environment. 4386 Fungicide means a substance, or mixture of subs tances, that destroys fungi (including 4387 yeasts) and fungal spores pathogenic to man or othe r animals in the inanimate environment. 4388 Microbiological water purifier means any unit, water treatment product or system that 4389 removes, kills or inactivates all types of disease- causing microorganisms from the water, including 4390 bacteria, viruses and protozoan cysts, so as to render the treated water safe for drinking. 4391
Sanitizer means a substance, or mixture of subs tances, that reduces the bacteria population 4392 in the inanimate environment by significant numbers, (e.g., 3 log 10 reduction) or more, but does 4393 not destroy or eliminate all bacteria. Sanitizer s meeting Public Health Ordinances are used on 4394 food contact surfaces and are termed sanitizing rinses. 4395
Sterilant means a substance, or mixture of substances, that destroys or eliminates all forms 4396 of microbial life in the inanimate environment, including all forms of vegetative bacteria, bacterial 4397 spores, fungi, fungal spores, and viruses. 4398
Tuberculocide means a substance, or mixture of substances, that destroys or irreversibly 4399
inactivates tubercle bacilli in the inanimate environment. 4400
Virucide means a substance, or mixture of substances, that destroys or irreversibly 4401
inactivates viruses in the inanimate environment. 4402 § 158.2204 Public health a nd nonpublic health claims. 4403 (a) Public health claim . An antimicrobial pesticide is considered to make a public health 4404 claim if the pesticide product bear s a claim to control pest microor ganisms that pose a threat to 4405*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 192 of 234 human health, and whose presence cannot readily be observed by the user, including but not 4406 limited to, microorganisms infectious to man in a ny area of the inanimate environment. A product 4407 makes a public health claim if one or more of the following apply: 4408 (1) A claim is made for control of specific microorganisms that are directly or indirectly 4409 infectious or pathogenic to man (or both man a nd animals). Examples of specific microorganisms 4410 include, but are not limited to:, Mycobacterium tuberculosis , Pseudomonas aeruginosa , 4411 Escherichia coli (E. coli), human immunode ficiency virus (HIV), Streptococcus, and 4412 Staphylococcus aureus . Claims for control of microorgani sms infectious or pathogenic only to 4413 animals (such as canine distemper virus or hog c holera virus) are not considered public health 4414
claims. 4415 (2) A claim is made for the pesticide product as a sterilant, disinfectant, virucide, 4416 sanitizer, or tuberculocide against microorganisms that are infectious or pathogenic to man. 4417 (3) A claim is made for the pesticide produc t as a fungicide against fungi infectious or 4418 pathogenic to man, or the product does not clearly state that it is intended for use only against 4419 nonpublic health fungi. 4420 (4) A claim is made for the pesticide product as a microbiological water purifier or 4421 microbial purification system. 4422 (5) A non-specific claim is made that the pesticide product will beneficially impact or 4423 affect public health at the site of use or in the environment in which it is applied, and: 4424 (i) The pesticide product contains one or more ingredients that, under the criteria in 40 4425 CFR 153.125(a), is an active ingredient with respect to a public health microorganism and there is 4426 no other functional purpose for the ingredient in the product; or 4427 (ii) The pesticide product is similar in co mposition to a registered pesticide product that 4428 makes antimicrobial public health claims. 4429*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 193 of 234 (b) Nonpublic health claim . An antimicrobial pesticide is considered to 4430 make a nonpublic health claim if the pesti cide product bears a claim to control 4431 microorganisms of economic or aesthetic si gnificance, where the presence of the 4432 microorganism would not normally lead to infection or disease in humans. 4433 Examples of nonpublic health claims incl ude, but are not lim ited to, algaecides, 4434 slimicides, preservatives and products for which a pesticidal claim with respect to 4435 odor sources is made. 4436 §158.2210 Product chemistry. 4437 The product chemistry dat a requirements of subpart D of this part apply to 4438 antimicrobial products covered by this subpart. 4439 §158.2220 Product performance. 4440 (a) General. (1) Product performance requirement for all antimicrobial 4441 pesticides . Each applicant must ensure th rough testing that his product is 4442 efficacious when used in accordance with label directions and commonly 4443 accepted pest control practices. The Agency may require, on a case-by-case 4444 basis, submission of product performance data for any pesticide product 4445 registered or proposed for registration or amendment. 4446 (2) Product performance data for each pr oduct that bears a public health 4447 claim . Each product that bears a public health claim, as described in 4448 §158.2204(a), must be supported by product performance data, as listed in the 4449 table in paragraph (c) of this secti on. Product performance data must be 4450 submitted with any application for registration or amended registration. 4451 (3) Product performance data for eac h product that bears a nonpublic 4452 health claim. Each product that bears a nonpublic health claim, as described in 4453*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 194 of 234 §158.2204(b), must be supported by product performance data. Each registrant 4454 must ensure through testing that his product is efficacious when used in 4455 accordance with label directions and comm only accepted practices. The Agency 4456 reserves the right to require, on a case -by-case basis, submission of product 4457 performance data for any pesticide product registered or proposed for registration 4458 or amendment. 4459 (4) Determination of data requirements . Subpart B of this part and 4460 §158.2201 describe how to use the table in paragraph (c) of this section to 4461 determine the product performance data requi rements for antimicrobial pesticide 4462 products. 4463 (b) Key. R = Required; EP = End-use product. 4464 (c) Table . The following table s hows the data requirements 4465 for antimicrobial produ ct performance. 4466 Table -- Antimicrobial Product Pe rformance Data Requirements 4467 Guidelin e Number Data Requirement All Use Patterns Test Substance

810.210 0 Sterilants – Efficacy Data Recommendations R EP 810.220 0 Disinfectants for Use on Hard Surfaces – Efficacy Data Recommendations R EP

810.230 0 Sanitizers for Use on Hard Surfaces – Efficacy Data Recommendations R EP

810.240 0 Disinfectants and Sanitizers for Use on Fabrics and Textiles -- Efficacy Data Recommendations R EP

810.250 0 Air Sanitizers – Efficacy Data Recommendations R EP 810.260 0 Disinfectants for Use in Water -- Efficacy Data Recommendations R EP 4468*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 195 of 234 §158.2230 Toxicology. 4469 (a) General. Subpart B of this part and § 158.2201 describe how to use 4470 the table in paragraph (g) of this sect ion to determine the toxicology data 4471 requirements for an antimicrobial pesti cide product. Notes that apply to an 4472 individual test including specific condition s, qualifications, or exceptions are listed 4473 in paragraph (h) of this section. 4474 (b) Uses. The applicant for registration must first dete rmine whether the 4475 use is likely to result in pesticide resi dues in food or water and therefore consult 4476 the “Food Use” columns of the table in parag raph (g) of this sect ion. Generally, if 4477 the residues of the antimicrobial result from an application to a surface or 4478 incorporated into a materi al that may come into c ontact with food or feed, and 4479 residues may be expected to tr ansfer to such food or fe ed, then the “Indirect Food 4480 Uses” columns is to be consulted. 4481 (c) Tiering of data requirements. Applicants for registration of 4482 antimicrobials may perform tests in a tier ed fashion. After the initially required 4483 tests are conducted, additional testing may be required if results of the initial tests 4484 trigger the need for additional data. Conditions that tr igger the need for additional 4485 data are given in the test notes in paragraph (h) of this section. 4486 (d) 200 ppb. The 200 ppb level was originally used by the Food and Drug 4487 Administration with respect to the concent ration of residues in or on food for 4488 tiering of data requirements for indirect food use biocides. The Agency has also 4489 adopted this same residue level for determi ning toxicology data requirements for 4490 indirect food uses of antimicrobial pesticides. The 200 ppb level is the 4491 concentration of antimicrobial resi dues in or on the food item. 4492*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***

Page 196 of 234 (e) Use of OSHA standards. If EPA determines that industrial standards, 4493 such as the workplace standards set by the Occupational Safety and Health 4494 Administration, provide adequate protec tion for a particular pesticide or a 4495 particular use pattern, additi onal toxicity data may not be required for that 4496 pesticide or the use pattern. 4497 (f) Key. R = Required; CR = Conditionally required; NR = Not required; 4498 MP = Manufacturing-use product; EP = E nd-use product; TGAI = Technical grade 4499 of the active ingredient; TEP = Typica l end-use product; PAI = Pure active 4500 ingredient; PAIRA = Pure active ingredien t, radiolabeled; Choice = choice of 4501 several test substances depending on studies required. 4502*** Deliberative Internal Document – DoNOT Cite, Quote, or Release ***(g)Table.The following table shows the data requirements for toxicology. The testnotes appear in paragraph (h)4503of this section.4504Table -- Antimicrobial Toxicology Data Requirements4505GuidelineNumberData RequirementFood Uses Nonfood Uses Test Substance TestNote No.DirectFoodUsesIndirectFoodUses (>200 ppb)IndirectFoodUses (≤200 ppb)Swimming Pools,Aquatic Areas,WoodPreservatives,Metal WorkingFluidsAll OtherNonfoodUsesMP EPAcute Testing870.1100 Acute oral toxicity – rat RRRRRMP andTGAIEP andTGAI1, 2870.1200 Acute dermal toxicity R R R R R MP andTGAIEP andTGAI1, 2, 3870.1300 Acute inhalation toxicity- ratR R R R R MP andTGAIEP andTGAI2, 4870.2400 Primary eye irritation -rabbitR R R R R MP andTGAIEP andTGAI1, 2, 3870.2500 Primary dermal irritation R R R R R MP andTGAIEP andTGAI1, 2, 3870.2600 Dermal sensitization R R R R R MP andTGAIEP andTGAI1, 2, 3, 5870.6200Acute neurotoxicity - rat R R CRR CR TGAI TGAI 6, 11Subchronic Testing870.310090-Day oral toxicity -rodentRR R R CR TGAI TGAI 8, 9, 15,38870.315090-Day oral toxicity -nonrodentR R CR R CR TGAI TGAI 10, 15870.320021/28-Day dermaltoxicityCR CR CR CR CR TGAI EP andTGAI12, 13*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***Page198of234870.325090-Day dermal toxicity CR CRCR CR CR TGAI EP andTGAI7, 13, 14,15870.3465 90-Day inhalation -toxicity - ratCR CR CR CR CR TGAI TGAI 7, 15, 16,17870.620090-Day neurotoxicity -ratR R CR R CR TGAI TGAI 6, 8Chronic Testing870.4100 Chronic oral toxicity -rodentR R CR R CR TGAI TGAI 18, 19,20870.4200 Carcinogenicity – tworodent species – rat andmouse preferredR R CR R CR TGAI TGAI 19, 21,22Developmental Toxicity and Reproduction870.3700 Prenatal developmentaltoxicity - rat and rabbitpreferredRR R R R TGAI TGAI 23, 24,25, 26870.3800 Reproduction andfertility effectsR R R R R TGAI TGAI 26, 27,28, 29870.6300 DevelopmentalneurotoxicityCR CR CR CR CRTGAI TGAI 28, 29,30Mutagenicity870.5100Reverse mutation assayRR R R R TGAI TGAI 31, 32870.5300870.5375In vitromammaliangene mutationR R R R R TGAI TGAI 31, 33870.5385870.5395In vivocytogenetics R R R R R TGAI TGAI 31, 34Special Testing870.7485 Metabolism andpharmacokineticsRR CR R CR PAI orPAIRAPAI orPAIRA35, 39870.7200 Companion animalsafetyCR CR CR CR CRNR Choice 36*** EO 12866 Draft – Do Not Cite, Quote or Release during Review ***Page199of234870.7600 Dermal penetration CRCR CR CR CR ChoiceChoice 3, 37870.7800 Immunotoxicity R RR R R TGAI TGAI 845064507 4508 ( h) Test notes. The following test notes appl y to the data requirements in 4509 the table to paragraph (g) of this section: 4510 1. Not required if test material is a gas or highly volatile liquid. 4511 2. The six end-use product (EP) acute toxi city studies are required using the product as 4512 formulated for sale and distribution. In addition, if the EP label has directions for diluting the 4513 product, then, the applicant may also need to conduc t certain of the acute toxicity studies using 4514 the highest concentration labeled for dilution (i.e . the least diluted product). The end-use dilution 4515 testing is in addition to the testing conducted on the EP. 4516 3. Not required if test material is corrosive to skin or has pH less than 2 or greater than 4517 11.5. 4518 4. Data are required when t he product consists of, or under conditions of use will result 4519 in, a respirable material (e.g., gas, vapor, aerosol or particulates). 4520 5. Data are required if repeated dermal exposure is likely to occur under conditions of 4521 use. 4522 6. For indirect food uses ≤ 200 ppb, and all other nonfood uses, data are required if the 4523 neurotoxicity screen in the 90-da y oral rodent study or other data indicate neurotoxicity. 4524 7. The 90-day dermal toxicity study and/or 90- day inhalation toxicity study are required if 4525 the Agency determines that dermal and/or inhalati on exposure is the primary route of exposure. 4526 8. All 90-day subchronic studies in the rodent can be designed to simultaneously fulfill 4527 the requirements of the 90-day neurotoxicity and/ or immunotoxicity studies by adding separate 4528 groups of animals for testing of neurotox icity and/or immunotoxicity parameters. 4529 9. The 90-day study is required in the rodent for hazard characterization (possibly 4530 endpoint selection) and dose-setting for the chronic/ carcinogenicity study. It is not required in the 4531 mouse, but the Agency would encourage the appl icant to conduct a 90-day range finding study 4532 for the purposes of dose selection for the m ouse carcinogenicity study to achieve adequate 4533 dosing and an acceptable study. 4534 10. A 1-year non-rodent study (i.e., 1-y ear dog study) may be required if the Agency 4535 finds that a pesticide chemical is highly bioacc umulative and slowly eliminated. EPA may also 4536 require the appropriate metabolism and pharmaco kinetic studies to evaluate more precisely 4537 bioavailability, half life, and steady state to deter mine if a longer duration dog toxicity study is 4538 needed. 4539 11. Although the subchronic toxicity testing guidelines include measurement of 4540 neurological endpoints, such screens do not meet the requirement of the 90-day neurotoxicity 4541 study. For nonfood uses, if the 90-day study doe s not include a neurotoxicity screen, then the 4542 acute neurotoxicity study will be required. 4543 12. Data are required if the intended use of the antimicrobial pesticide product is 4544 expected to result in repeated, dermal human ex posure to the product, data from a subchronic 4545 90-day dermal toxicity study are not available, and the 90-day dermal toxicity study has not been 4546 triggered. 4547 13. EP testing is required if the product or any component of the product may increase 4548 dermal absorption of the active ingredient(s) or increases its toxic or pharmacologic effects, as 4549 determined by testing using the TGAI or based on av ailable information about the toxic effects of 4550 the product or its components. 4551 14. Data are required if the active ingredi ent in the product is known or expected to be 4552 metabolized differently by the derma l route of exposure than by the oral route, and a metabolite of 4553 the active ingredient is the toxic moiety. 4554 15. A 90-day oral toxicity test is not requ ired for heating, ventilation, air conditioning, and 4555 refrigeration systems (collectivel y referred to as HVAC&R). In stead two 90-day toxicity tests, one 4556 by the dermal route and one by the inhalation route are required. 4557 16. Data are required if there is the likel ihood of significant repeated inhalation exposure 4558 to the pesticide as a gas, vapor, or aerosol. 4559*** Deliberative Internal Document – Do NOT Cite, Quote, or Release *** 201

17. Based on estimates of the magnitude and duration of human exposure, studies of 4560 shorter duration, e.g., 21- or 28-days, may be su fficient to satisfy this requirement. The prime 4561 consideration in determining the appropriateness of a shorter duration study is the likely period of 4562 time for which humans will be exposed. 4563 18. Based on the positive results of the ac ute or 90-day neurotoxicit y studies, or on other 4564 data indicating neurotoxicity, a ch ronic neurotoxicity study (i.e. a chronic study with additional 4565 neurotoxicity evaluations) may be required to pr ovide information about potential neurotoxic 4566 effects from long-term exposures. 4567 19. Studies which are designed to simult aneously fulfill the requirements of both the 4568 chronic oral and carcinogenicity studies (i .e., a combined study) may be conducted. 4569 20. For indirect food uses ≤ 200 ppb, and all other nonfood uses, data are required if 4570 either of the following criteria are met: 4571 i. The use of the pesticide is likely to result in repeated human exposure over a 4572 considerable portion of the human lifespan; or 4573 ii. The use requires that a tolerance, tolera nce exemption, or food additive regulation or 4574 clearance be established. 4575 21. For indirect food uses ≤ 200 ppb, and all other nonfood uses, data are required if any 4576 of the following criteria, are met: 4577 i. The use of the pesticide is likely to result in significant human exposure over a 4578 considerable portion of the human life span which is significant in terms of frequency, time, 4579 duration, and/or magnitude of exposure. 4580 ii. The use requires that a tolerance, tolera nce exemption, or food additive regulation or 4581 clearance be established. 4582 iii. The active ingredient, metabolite, degradate, or impurity: 4583 A. Is structurally related to a recognized carcinogen; 4584 B. Causes mutagenic effects as demonstrated by in vitro or in vivo testing; or 4585 C. Produces a morphologic effect in any organ (e.g., hyperplasia, metaplasia) in 4586 subchronic studies that may lead to a neoplastic change. 4587 22. If the requirement for a carcinogenicity study in any species is modified or waived for 4588 any reason, then a subchronic 90-day oral study in the same species may be required. 4589 23. Testing in two species is required for all uses. 4590 24. The oral route, by oral intubation, is preferred, unless the chemical or physical 4591 properties of the test substance, or the patte rn of human exposure, suggest a more appropriate 4592 route of exposure. 4593 25. Additional testing by other routes of exposure may be required if the pesticide is 4594 determined to be a prenatal developmental toxicant after oral dosing. 4595 26. The developmental toxicity study in rodents may be combined with the two4596 generation reproduction study in rodents by using a second mating of the parental animals in 4597 either generation. Protocols must be approved by th e Agency prior to the initiation of the study. 4598 27. A two-generation reproduction study is required. 4599 28. An information-based approach to test ing is preferred, which utilizes the best 4600 available knowledge on the chemical (hazard, pha rmacokinetic, or mechanistic data) to determine 4601 whether a standard guideline study, an enhanced guide line study, or an alternative study should 4602 be conducted to assess potential hazard to the developing animal. Applicants must submit any 4603 alternative proposed testing protocols and supportin g scientific rationale to the Agency. Protocols 4604 must be approved by the Agency prior to the initiation of the study. 4605 29. The use of a combined two-generati on reproduction/developmental neurotoxicity 4606 study that utilizes the two-gener ation reproduction study in rodent s as a basic protocol for the 4607 addition of other endpoints or functional assessm ents in the immature animal is encouraged. 4608 30. A DNT study is required using a weight-of-evidence approach when: 4609 i. The pesticide causes treatment-related neur ological effects in adult animal studies (i.e, 4610 clinical signs of neurotoxicity, neuropathol ogy, functional or behavioral effects). 4611 ii. The pesticide causes treatment-related neurological effects in developing animals, 4612 following pre- or postnatal exposure (i.e., nerv ous system malformations or neuropathy, brain 4613 weight changes in offspring, functional or behavioral changes in the offspring). 4614*** Deliberative Internal Document – Do NOT Cite, Quote, or Release *** 202

iii. The pesticide elicits a causative association between exposures and adverse 4615 neurological effects in human epidemiological studies. 4616 iv. The pesticide evokes a mechanism that is associated with adverse effects on the 4617 development of the nervous system (i.e., stru cture-activity-relation ship (SAR) to known 4618 neurotoxicants, altered neuroreceptor or neurotransmitter responses). 4619 31. To facilitate the weight-of-evidence determination for the pesticide’s mutagenicity, 4620 the Agency requires submission of other mutagenicity test results, besides those specifically 4621 listed in this table, that may have been perform ed. A reference list of all studies and papers 4622 known to the applicant concerning the mutagenicity of the test chemical must be submitted with 4623 the required studies. 4624 32. Due to the nature of antimicrobials, if testing with bacterial strains has not been 4625 conducted, then testing using a mammalian cell assay such as the mouse lymphoma TK +/- 4626 assay is preferred. If reverse mutation assay testing with bacterial strains has already been 4627 conducted, and the testing was conducted at levels that did not cause toxicity to the bacterial 4628 strains tested, then the applicant may submit the study to fulfill this data requirement. 4629 33. For the in vitro mammalian gene mutation study, there is a choice of assays using 4630 either mouse lymphoma L5178Y cell thymidine ki nase (tk) gene locus, maximizing assay 4631 conditions for small colony expression and detec tion; Chinese hamster ovary (CHO) or Chinese 4632 hamster lung fibroblast (v79) cells, hypoxant hine-guanine phosphoribosy l transferase (hgprt) 4633 gene locus, accompanied by an appropriate in vitro test for clastogenicity; or CHO cells strains 4634 AS52, xanthine-guanine phosphoribosyl transferase (xprt) gene locus. 4635 34. There is a choice of assays, but the micronucleus rodent bone marrow assay is 4636 preferred; the rodent bone marrow assays us ing metaphase analysis (aberrations) are 4637 acceptable. 4638 35. Data are required when chronic toxicity or carcinogenicity studie s are also required. 4639 36. Data is required if the product label directs that it be applied to domestic animals, 4640 such as cats, dogs, cattle, pigs, and horses

. 4641 37. In the absence of dermal absorption data or a repeated dose dermal toxicity study, 4642 the assumption of 100% dermal absorption would be used in a risk assessment to determine if a 4643 dermal penetration study is required, and to ident ify the doses and duration of exposure for which 4644 dermal absorption is to be quantified. 4645 38. Required for nonfood uses, if oral exposure could occur. 4646 39. Data may be required if significant adverse effects are seen in 4647 available toxicology studies and these effects can be further elucidated by 4648 metabolism and pharmacokinetics studies. 4649 § 158.2240 Nontarget organisms. 4650 (a) General . Subpart B of this part and § 158.2201 describe how to use 4651 the table in paragraph (c) of this secti on to determine the terrestrial and aquatic 4652 nontarget organisms data requi rements for a particular antimicrobial pesticide 4653 product. Notes that apply to an individual test including specific conditions, 4654 qualifications, or excepti ons are listed in paragraph (d) of this section. 4655 (1) Terrestrial and aquatic nontar get organism data are required to 4656 support the registration of most end-us e and manufacturing-use antimicrobial 4657 products. 4658*** Deliberative Internal Document – Do NOT Cite, Quote, or Release *** 203 (2) Data are generally not required to support end-use products of a gas, 4659 highly volatile liquid, highly reactive so lid, or a highly corrosive material. 4660 (3) Data on transformation/degradation products or leachate residues of 4661 the parent compound are al so required to support registration, if the 4662 transformation/degradation/leachate products meet one of the following criteria: 4663 (i) More toxic, persistent, or bioaccumulative than the parent; 4664 (ii) Have been shown to cause adver se effects in mammalian or aquatic 4665 reproductive studies; or 4666 (iii) The moiety of concern (i.e., functional group in the parent chemical 4667 molecule that imparts adverse effects) remains intact. 4668 (4) If an antimicrobial may be applied to a field crop, horticultural crop, or 4669 turf, then the data require ments in §158.630 apply. 4670 (5) For the purpose of determining dat a requirements, the All Other use 4671 patterns category includes t he following use patterns: 4672 (i) Agricultural premises and equipment. 4673 (ii) Food-handling/stor age establishments, premises, and equipment. 4674 (iii) Commercial, institutional a nd industrial premises and equipment. 4675 (iv) Residential and public access premises. 4676 (v) Medical premises and equipment. 4677 (vi) Human drinking water systems. 4678 (vii) Materials preservatives. 4679 (viii) Swimming pools. 4680*** Deliberative Internal Document – Do NOT Cite, Quote, or Release *** 204 (b) Key. MP = Manufacturing use product; EP = End-use product; R = 4681 Required; CR = Condit ionally required; NR = Not r equired; TGAI = Technical 4682 grade of the active ingredient; TEP = Typical end-use product; PAIRA = Pure 4683 active ingredient radiolabeled ; a.i. = active ingredient. 4684 4685(c)Table.The following table shows the data requirements fornontarget organisms. The test notes appear4686in paragraph (d) of this section.4687Table -- Antimicrobial Nontarget Organism DataRequirements4688GuidelineNumberDataRequirementUse Pattern TestSubstanceTestNoteNo.IndustrialProcessesand WaterSystemsAntifoulantCoatings andPaintsWoodPreservativesAquaticAreasAllOtherUsePatternsCategoryMP EPTier One Testing850.2100 Acute avian oraltoxicityR R R R R TGAI TGAI 1850.1010 AcutefreshwaterinvertebratestoxicityR R R R R TGAI TGAI 2850.1075 Acutefreshwater fishtoxicityR R R R R TGAI TGAI 3Higher Tier TestingAvian Testing850.2200 Avian dietarytoxicityCR CR CR CR CRTGAI TGAI 4850.2300 AvianreproductionCR CR CR CR CRTGAI TGAI 1, 6Aquatic Organisms Testing*** Deliberative Internal Document – DoNOT Cite, Quote, or Release ***206GuidelineNumberDataRequirementUse Pattern TestSubstanceTestNoteNo.IndustrialProcessesand WaterSystemsAntifoulantCoatings andPaintsWoodPreservativesAquaticAreasAllOtherUsePatternsCategoryMP EP850.1010 AcutefreshwaterinvertebratestoxicityCR CR CR CR CR --- TEP 2, 5, 7850.1075 Acutefreshwater fishtoxicityCRCR CR CR CR --- TEP 3, 5, 7850.1025850.1035850.1045850.1055850.1075Acute estuarineand marineorganismstoxicityCR R CR CR CRTGAI TGAI 8, 9Acute estuarineand marineorganismstoxicityCR CR CR CR CR --- TEP 5, 7, 8850.1400 Fish early-lifestageRR R R R TGAI TGAI 10850.1300850.1350Aquaticinvertebrate lifecycleRR R R R TGAI TGAI 10850.1500 Fish life-cycle CR CRCR CR CR TGAI TGAI 11, 12850.1710 Aquatic CR CR CRCR CR TGAI. TGAI. 13*** Deliberative Internal Document – DoNOT Cite, Quote, or Release ***207GuidelineNumberDataRequirementUse Pattern TestSubstanceTestNoteNo.IndustrialProcessesand WaterSystemsAntifoulantCoatings andPaintsWoodPreservativesAquaticAreasAllOtherUsePatternsCategoryMP EP850.1730850.1850organisms,bioavailability,biomagnification, toxicity testsPAI,degradatePAI,degradate850.1950 Simulated oractual fieldtesting foraquaticorganismsCR CR CR CR CR TEP TEP 14,15, 16Sediment Testing850.1735 Wholesediment; acutefreshwaterinvertebratesCR CR CR CR CRTGAI TGAI 15, 17850.1740 Wholesediment; acutemarineinvertebratesCR CR CR CR CRTGAI TGAI 15,17, 19None Wholesediment;chronicinvertebratesCR CR CR CR CRTGAI TGAI 15,18, 19*** Deliberative Internal Document – DoNOT Cite, Quote, or Release ***208GuidelineNumberDataRequirementUse Pattern TestSubstanceTestNoteNo.IndustrialProcessesand WaterSystemsAntifoulantCoatings andPaintsWoodPreservativesAquaticAreasAllOtherUsePatternsCategoryMP EPfresh-water andmarineInsect Pollinator Testing850.3020 Honeybee acutecontactNR NR R NR CRTGAI TGAI 20850.3030 Toxicity ofresidues tohoneybeesNR NR R NR CR TGAI TEPortreatedwood20, 214689*** Deliberative Internal Document – Do NOT Cite, Quote, or Release *** 209

4690 (d) Test notes . The following test notes appl y to the data requirements in 4691 the table to paragraph (c) of this section: 4692 1. For industrial processes and water systems, antifoulant paints and coatings, wood 4693 preservatives, and aquatic areas, data are required for two avian species: one waterfowl species 4694 and one upland game bird species. For the all other use patterns category (as specified in § 4695 158.2240(a)(5)), data are required for one avian species. 4696 2. Data are required on one freshwater aquatic invertebrate species. 4697 3. For the industrial processes and water systems, antifoulant paints and coatings, wood 4698 preservatives, and aquatic areas, data are required on two species of fish, one coldwater species 4699 and one warmwater species. For the all other” use patterns category (as specified in § 4700 158.2240(a)(5)), data are required on one species of fish, either one coldwater species or a 4701 warmwater species. Testing on a second species is required if the active ingredient or principal 4702 transformation products are stable in the environment and the LC 50 in the first species is greater 4703 than 1 ppm or 1 mg/L. 4704 4. Data are required on one avian species, either one waterfowl species or one upland 4705 game bird species, if the avian acute oral LD 50 ( TGAI testing) is less than or equal to 100 mg. 4706 a.i./kg and a.i. residues or its principal transform ation products are likely to occur in avian feed 4707 items. Data on the second species are required if the avian dietary LC 50 in the first species tested 4708 is less than or equal to 500 ppm a.i. in the diet. 4709 5. If TEP testing cannot be conducted due to the physical characteristics of the test 4710 substance (for example, a paint), t hen the applicant should request a waiver. 4711 6. Data are required if one or more of the following criteria are met: 4712 i. Birds may be subjected to repeated or c ontinued exposure to the pesticide or any of its 4713 transformation products, especially preceding or during the breeding season. 4714 ii. The pesticide or any of its major metabo lites or degradation products are stable in the 4715 environment to the extent that a potentially toxic amount may persist in avian feed. 4716 iii. The pesticide or any of its major metabo lites or degradation products are stored or 4717 accumulated in plant or animal tissues, as indica ted by the octanol/water partition coefficient (K ow 4718 is greater than or equal to 1,000), accumulation studies, metabolic release and retention studies, 4719 or as indicated by structural similari ty to known bioaccumulative chemicals. 4720 iv. Any other information, such as that derived from mammalian reproduction studies, 4721 indicates that reproduction in terrestrial verteb rates may be adversely affected by the anticipated 4722 use of the pesticide product. 4723 7. TEP testing is required for any produ ct which meets one or more of the following 4724 conditions: 4725 i. When based on deterministic modeling results: If the Estimated Environmental 4726 Concentration (EEC) in the aquatic environment is equal to or greater than one-half the LC 50 /EC 50 4727 of the TGAI. 4728 ii. When based on probabilistic modeling results: If the estimated 10 th percentile 7Q10 4729 Surface Water Concentration exceeds the acut e concentration of concern (i.e., one-half the 4730 LC 50 /EC 50 ) for 4 or more days. 4731 iii. If an ingredient in the end-use product other than the active ingredient is expected to 4732 enhance the toxicity of the active ingredient or to cause toxicity to aquatic organisms. 4733 iv. The end-use antimicrobial product will be applied directly into an aquatic environment. 4734 8. Data are required on one estuarine/ marine mollusk, one other estuarine/marine 4735 invertebrate, and one estuarine/marine fish species. 4736 9. For the all other use patterns category (as specified in § 158.2240(a)(5)), industrial 4737 processes and water systems, wood preservative s, and aquatic areas, data are required if the 4738 pesticide residues from the parent compound and/or transformation products are likely to enter 4739 the estuarine/marine environment. 4740 10. Testing must be conducted with the most sensitive organism (either freshwater or 4741 estuarine/marine vertebrates, or freshwater or estuarine/marine invertebrates), as determined 4742*** Deliberative Internal Document – Do NOT Cite, Quote, or Release *** 210

from the results of the acute toxicity tests (acute EC 50 freshwater invertebrates; acute LC 50 /EC 50 4743 estuarine and marine organisms; acute freshwater fish LC 50 ). 4744 11. Data are required on estuarine/marine sp ecies if the product is intended for direct 4745 application to the estuarine or marine environm ent, or the product is expected to enter this 4746 environment in significant concentrations becau se of its expected use or mobility patterns. 4747 12. Data are required on freshwater species if the end-use product is intended to be 4748 applied directly to water, or is expected to be tr ansported to water from the intended use site, and 4749 when one or more of the following conditions apply: 4750 i. When based on deterministic modeling results: If the Estimated Environmental 4751 Concentration (EEC) in water is equal to or gr eater than 0.1 of the no-observed-adverse-effect 4752 concentration or no-observed-adverse-effect level (NOAEC/NOAEL) in the fish early-life stage or 4753 invertebrate life cycle tests. 4754 ii. When based on probabilistic modeling results: If the estimated 10 th percentile 7Q10 4755 Surface Water Concentration based on probabilistic modeling exceeds for 20 days or more the 4756 chronic concentration of concer n (i.e., one-tenth the NOAEC or NOAEL) determined in the fish 4757 early-life stage or invertebrate life cycle tests. 4758 iii. If studies of other orga nisms indicate that the reprodu ctive physiology of fish may be 4759 affected. 4760 13. Not required when: 4761 i. The octanol/water partition coefficients of the pesticide and its major degradates are 4762 less than 1,000; 4763 ii. There are no potential exposures to fish and other nontarget aquatic organisms; or 4764 iii. The hydrolytic half-life is le ss than 5 days at pH 5, 7, and 9. 4765 14. Environmental chemistry methods used to generate data associated with this study 4766 must include results of a successful confirmatory method trial by an independent laboratory. Test 4767 standards and procedures for independent laborat ory validation are available as addenda to the 4768 guideline for this test requirement. 4769 15. Protocols must be approved by the Agen cy prior to the initiation of the study. 4770 16. Data are required if the intended use pattern, and the physical/chemical properties 4771 and environmental fate characteristic s of the antimicrobial indicate significant potential exposure, 4772 and, based on the results of the acute and ch ronic aquatic organism testing, significant 4773 impairment of nontarget aquatic organisms could result. 4774 17. Data are required if the half-life of the pesticide in the sediment is equal to or less 4775 than 10 days in either the aerobic soil or aquatic metabolism studies, and if one or more of the 4776 following conditions are met: 4777 i. The soil partition coefficient (K d ) is equal to or greater than 50 L/kg. 4778 ii. The log K ow is equal to or greater than 3. 4779 iii. The K oc is equal to or greater than 1,000. 4780 18. Data are required if the EEC in s ediment is greater than 0.1 of the acute LC 50/ EC 50 4781 values and if one or more of the following conditions are met: 4782 i. The soil partition coefficient (K d ) is equal to or greater than 50 L/kg. 4783 ii. The log K ow is equal to or greater than 3. 4784 iii. The K oc is equal to or greater than 1,000. 4785 19. Sediment testing with estuarine/mari ne test species is required if the product is 4786 intended for direct application to the estuarine or marine environment or the product is expected 4787 to enter this environment in significant concentrat ions either by runoff or erosion, because of its 4788 expected use or mobility pattern. 4789 20. For the all other use patterns category (as specified in § 158.2240(a)(5)), data are 4790 required only for beehive applications when the beehive (empty or occupied) may be treated. 4791 21. A study similar to “Honey Bee Toxici ty of Residues on Foliage” is required using 4792 treated wood instead of the foliage. Protocol s must be approved by the Agency prior to the 4793 initiation of the study. 4794 §158.2250 Nontarget plant protection. 4795*** Deliberative Internal Document – Do NOT Cite, Quote, or Release *** 211 (a) Subpart B of this part and § 158.2201 describe how to use the table in 4796 paragraph (f) of this sect ion to determine the nontarget plant protection data 4797 requirements for a particular antimicrobial pesticide product. Notes that apply to 4798 an individual test including specific condi tions, qualifications, or exceptions are 4799 listed in paragraph (g) of this section. 4800 (b) Data on transformation/degradation products or leachate residues of 4801 the parent compound are also required to support r egistration, if the 4802 transformation/degradation/leachate products meet one of the following criteria: 4803 (i) More toxic, persistent, or bioaccumulative than the parent; 4804 (ii) Have been shown to cause adver se effects in mammalian or aquatic 4805 reproductive studies; or 4806 (iii) The moiety of concern (i.e., functional group in the parent chemical 4807 molecule that imparts adverse effects) remains intact. 4808 (c) For the purpose of determining dat a requirements, the All Other use 4809 patterns category includes t he following use patterns: 4810 (i) Agricultural premises and equipment. 4811 (ii) Food-handling/stor age establishments, premises, and equipment. 4812 (iii) Commercial, institutional a nd industrial premises and equipment. 4813 (iv) Residential and public access premises. 4814 (v) Medical premises and equipment. 4815 (vi) Human drinking water systems. 4816 (vii) Materials preservatives. 4817 (viii) Swimming pools. 4818*** Deliberative Internal Document – Do NOT Cite, Quote, or Release *** 212 (d) If an antimicrobial may be applied to a field crop, horticultural crop, or 4819 turf, then the data requirem ents in 40 CFR 158.660 apply. 4820 (e) Key. MP = Manufacturing use pr oduct; EP = End-use product; R = 4821 Required; CR = Condit ionally required; NR = Not required; TGAI = Technical 4822 grade of the active ingredient; TEP = Typical end-use product. 4823*** Deliberative Internal Document – DoNOT Cite, Quote, or Release ***213(f)Table.The following table shows the data requirements for nontarget plant protection. The test notes appear in4824paragraph (g) of this section.4825Table -- Nontarget Plant Protection Data Requirements4826GuidelineNumberDataRequirementUse Pattern TestSubstanceTestNoteNo.IndustrialProcessesand WaterSystemAntifoulantCoatings andPaintsWoodPreservativesAquaticAreasAllOtherUsePatternsCategoryMP EP850.4225 Seedlingemergence, TierII – doseresponseCR CRCR CR CR TEP TEP 1, 2850.4250 Vegetative vigor, Tier II – doseresponseCR NR CR CR CR TEP TEP 1, 3850.4400 Aquatic plantgrowth (aquaticvascular plant)Tier II – doseresponseR R R R CR TGAI,TEPTGAI,TEP4, 10850.5400Aquatic plantgrowth (algal)Tier II (doseresponse)R R R R RTGAI,TEPTGAI,TEP4, 5, 6*** Deliberative Internal Document – DoNOT Cite, Quote, or Release ***214GuidelineNumberDataRequirementUse Pattern TestSubstanceTestNoteNo.IndustrialProcessesand WaterSystemAntifoulantCoatings andPaintsWoodPreservativesAquaticAreasAllOtherUsePatternsCategoryMP EP850.4300 Terrestrial field CRCRCRCRCRTEP TEP 7, 8, 9850.4450 Aquatic field CRCRCRCRCRTEP TEP 7, 8, 94827(g) Test notes. The following test notes apply to the data requirements in 4828 the table to paragraph (f) of this section: 4829 1. Data on only one plant species (rice, Oryza sativa ) are required. 4830 2. Data are required if the risk quotient from any aquatic plant growth Tier II study 4831 exceeds a level of concern for aquatic plants. 4832 3. Not required when: 4833 i. There are no potential exposures to plants; 4834 ii. The hydrolytic half-life is less than 5 days at pH 5, 7, and 9; or 4835 iii. The results of a biodegradation study indi cate that the active ingredient or principal 4836 degradation products are not biodegradable in 28 days, i.e. the biodegr adation curve has not 4837 reached a plateau for at least three determinations within the 28 days. 4838 4. For TEP testing, data are required fo r the applicant’s end-use pr oduct if an ingredient 4839 in the end-use product, other than the active ingredi ent, is expected to enhance the toxicity of the 4840 active ingredient. 4841 5. One Tier II (dose response) study, conducted with Selenastrum capricornutum, is 4842 required for the all other use patterns category (as specified in § 158.2250(c)). If the results of 4843 this study exhibit detrimental effects (EC 50 less than 1.0 ppm or mg/L), then additional Tier II 4844 (dose response) studies are required on three species ( Anabaena flos-aquae, Navicula 4845 pelliculosa, and Skeletonema costatum). 4846 6. For industrial processes and water syst ems, antifoulant coatings and paints, wood 4847 preservatives, and aquatic areas, Tier II (dose response) studies are required on four species 4848 ( Anabaena flos-aquae, Navicula pe lliculosa, Skeletonema costatum, and Selenastrum 4849 capricornutum ). 4850 7. Environmental chemistry methods used to generate data must include the results of a 4851 successful confirmatory method tr ial by an independent laboratory. 4852 8. Tests are required on a case-by-case basis based on the results of lower tier plant 4853 protection studies, adverse incident reports, intended use pattern, and environmental fate 4854 characteristics that indicate potential exposure. 4855 9. Protocols must be approv ed by the Agency prior to the initiation of the study. 4856 10. For the all other use patterns category (as specified in § 158.2250(c)), data are 4857 required if the aquatic (algal) plant growth Tier II study demonstrates detrimental effects at less 4858 than 1.0 ppm or mg/L. 4859 §158.2260 Applicator exposure. 4860 (a) General. Subpart B of this part and § 158.2201 describe how to use 4861 the table in paragraph (d) of this sect ion to determine the applicator exposure 4862 data requirements for antimic robial pesticide products. Notes that apply to an 4863 individual test including specific condition s, qualifications, or exceptions are listed 4864 in paragraph (e) of this section. 4865 (1) The Agency may accept surrogat e exposure data estimations and/or 4866 modeling estimations from other sources to satisfy exposure data requirements. 4867 The surrogate data must meet the basic quality assuranc e, quality control, good 4868*** Deliberative Internal Document – Do NOT Cite, Quote, or Release *** 216 laboratory practice, and other scientif ic requirements set by EPA. To be 4869 acceptable, the Agency must find that the surrogate exposure data estimations 4870 have adequate information to address the applicable exposure data requirements 4871 and contain adequate monitoring events of acceptable qualit y. The data must 4872 reflect the specific use prescribed on t he label and the activity of concern, 4873 including formulation type, application me thods and rates, type of activity, and 4874 other pertinent information. 4875 (2) Occupational uses include no t only handlers, mixers, loaders, and 4876 applicators, but also commercial applications to residential sites. Residential 4877 uses are limited to non-occupational, i.e., non-professional, antimicrobial 4878 applications. Both occupational and resi dential applicator data may be required 4879 for the same product. 4880 (b) Criteria for testing . Applicator exposure data described in the table to 4881 paragraph (d) of this section are required based on toxicity and exposure criteria. 4882 Data are required if at leas t one of the toxicity criteria in paragraph (b)(1) of this 4883 section, and at least one of the exposur e criteria in paragr aph (b)(2) of this 4884 section are met. 4885 (1) Toxicity criteria. (i) Evidence of potentially significant adverse effects 4886 have been observed in any applicable toxicity studies. 4887 (ii) Scientifically s ound epidemiological or poi soning incident data with a 4888 clear cause-effect relationship indicati ng that adverse health effects may have 4889 resulted from exposure to the pesticide. 4890*** Deliberative Internal Document – Do NOT Cite, Quote, or Release *** 217 (2) Exposure criteria. --(i) Dermal exposure may occur during product 4891

use. 4892 (ii) Respiratory exposure ma y occur during product use. 4893 (c) Key. R = Required; CR = Conditionally required; TEP = Typical end4894 use product. 4895 (d) Table. The following table shows the data requirements for applicator 4896 exposure. The test notes appear in paragraph (e) of this section. 4897 Table -- Antimicrobial Applic ator Exposure Data Requirements 4898 Guidelin e Number Data Requirements Use Sites Test Substan ce Test Note No. Occupational Residential 875.110 0 875.120 0 Dermal exposure R R TEP 1, 2, 3, 4

875.130 0 875.140 0 Inhalation exposure R R TEP 1, 2, 3, 4

875.150 0 Biological monitoring CR CR TEP 1, 2, 3
875.160 0 Data reporting and calculations R R TEP 5 875.170 0 Product use information R R TEP --
4899 (e) Test notes. The following test notes appl y to the data requirements in 4900 the table to paragraph (d) of this section: 4901 1. Prior to initiation of the study, protoc ols involving intentional exposure of human 4902 subjects must be submitted for review by EPA and then the Human Studies Review Board 4903 (HSRB) according to 40 CFR 26.1125. Examples of proposed human study research can be 4904 found in various reviews provided by the Human Studies Review Board 4905 ( http://www.epa.gov/os a/hsrb/index.htm ). 4906 2. Biological monitoring data may be submitted in addition to, or in lieu of, dermal and 4907 inhalation passive dosimetry exposure data, provided the human pharmacokinetics of the 4908 pesticide or metabolite/analog compounds ( i.e. , whichever method is selected as an indicator of 4909 body burden or internal dose) allow for the ba ck calculation to the total internal dose. 4910*** Deliberative Internal Document – Do NOT Cite, Quote, or Release *** 218

3. For products with both indoor and outdoor uses, and similar conditions of use, data 4911 are generally required for the indoor applicatio ns only. However, data for outdoor uses are 4912 required if the Agency expects outdoor uses to re sult in greater exposure than indoor uses (e.g., 4913 higher use rates and application frequency, or longer exposure duration, or application 4914 methods/equipment create potential for increased dermal or inhalation exposure in outdoor 4915 versus indoor use sites). In certain cases, when a pesticide may be used both indoors and 4916 outdoors under dissimilar conditions of use, the Agency may require submission of applicator 4917 exposure data for both use patterns. 4918 4. EPA will consider waiving this data requi rement for antimicrobials applied via closed 4919 loading systems if the antimicrobial has a low vapor pressure. 4920 5. Data reporting and calculations are required only if handler exposure data are 4921 required. 4922 §158.2270 Post-application exposure

. 4923 (a) General. Subpart B of this part and § 158.2201 describe how to use 4924 the table in paragraph (d) of this se ction to determine the post-application 4925 exposure data requirements for anti microbial pesticide products. The data 4926 generated during these studies are used to determine the quantity of pesticide to 4927 which people may be exposed after applicati on. Notes that apply to an individual 4928 test, including specific conditions, qualific ations, or exceptions to the designated 4929 test, are listed in paragr aph (e) of this section. 4930 (1) Post-application exposure data are required when certain toxicity 4931 criteria are met and the human activiti es associated with the pesticide's use 4932 pattern can lead to potential adverse exposures. 4933 (2) The Agency may accept surrogat e exposure data estimations and/or 4934 modeling estimations from other sources to satisfy exposure data requirements. 4935 The surrogate data must meet the basic quality assuranc e, quality control, good 4936 laboratory practice, and other scientif ic requirements set by EPA. To be 4937 acceptable, the Agency must find that the surrogate exposure data estimations 4938 have adequate information to address the applicable exposure data requirements 4939 and contain adequate monitoring events of acceptable qualit y. The data must 4940*** Deliberative Internal Document – Do NOT Cite, Quote, or Release *** 219 reflect the specific use prescribed on t he label and the activity of concern, 4941 including formulation type, application me thods and rates, type of activity, and 4942 other pertinent information. 4943 (b) Criteria for testing. Post-application exposu re data described in the 4944 table to paragraph (d) of this section are required based on toxicity and exposure 4945 criteria. Data are required if at least one of the toxicity criteria in paragraph (b)(1) 4946 of this section, and at least one of the ex posure criteria in par agraph (b)(2) of this 4947 section are met. 4948 (1) Toxicity criteria. --(i) Evidence of potentially significant adverse effects 4949 have been observed in any applicable toxicity studies. 4950 (ii) Scientifically s ound epidemiological or poi soning incident data with a 4951 clear cause-effect relationship indicati ng that adverse health effects may have 4952 resulted from exposure to the pesticide. 4953 (2) Exposure criteria. --(i) Outdoor uses. (A) Occupational human post4954 application or bystander exposure to resi dues of antimicrobial pesticides could 4955 occur as the result of, but is not limited to , worker re-entry in to treatment sites, 4956 clean-up and equipment maintenance tasks, handling wood preservative-treated 4957 wood, or other work-related activity. 4958 (B) Residential human post-applicati on or bystander exposure to residues 4959 of antimicrobial pesticides could occur fo llowing the applicati on of antimicrobials 4960 pesticides to outdoor areas and spaces at residential sites, such as, but not 4961 limited to homes, daycare center s, and other public buildings. 4962*** Deliberative Internal Document – Do NOT Cite, Quote, or Release *** 220 (ii) Indoor uses. (A) Occupational human po st-application or bystander 4963 exposure to pesticide re sidues could occur following the application of the 4964 antimicrobial pesticide to indoor spaces or surfaces. 4965 (B) Residential human post-applic ation or bystander exposure to 4966 pesticide residues could occur following the application of the antimicrobial 4967 pesticide to indoor spaces or surfaces at residential sites, such as, but not limited 4968 to homes, daycare centers, hospitals , schools, and other public buildings. 4969 (c) Key. R = Required; CR = Conditionally required; NR = Not required; 4970 TEP = Typical end-use product. 4971 (d) Table. The following table shows t he data requirements for post4972 application exposure. The test notes appear in paragraph (e) of this section. 4973 Table -- Antimicrobial Post-App lication Exposure Data Requ irements. 4974 Guideline Number Data Requirement Use Sites Test Substance to Support Test Note No. Occupational Residential 875.2200 Soil residue dissipation CR CR TEP 2, 3 875.2300 Indoor surface residue dissipation CR R TEP 3, 4, 5, 6

875.2400 Dermal exposure CR CR TEP 1, 7, 8 875.2500 Inhalation exposure CR CR TEP 1,7, 8, 9 875.2600 Biological monitoring CR CR TEP 1, 8
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 10 4975*** Deliberative Internal Document – Do NOT Cite, Quote, or Release *** 221 (e) Test notes. The following test notes appl y to the data requirements in 4976 the table to paragraph (d) of this section: 4977 1. Prior to initiation of the study, protoc ols involving intentional exposure of human 4978 subjects must be submitted for review by EPA and then the Human Studies Review Board 4979 (HSRB) according to 40 CFR 26.1125. Examples of proposed human study research can be 4980 found in various reviews provided by the Human Studies Review Board (HSRB) 4981 ( http://www.epa.gov/os a/hsrb/index.htm). 4982 2. For residential wood preservative uses , data may be required if soil has the potential 4983 to be an important exposure pathw ay, and soil is in contact with or adjacent to treated wood, 4984 including but not limited to decks, play sets, and gazebos, 4985 3. Protocols must be approv ed by the Agency prior to the initiation of the study. 4986 4. For wood preservatives, data are requir ed for treated wood surfaces where post4987 application contact with treated wood is anticipated. 4988 5. For occupational uses, data are required if the pesticide may be applied to or around 4989 surfaces, and if the human activity data indicate that workers are likely to have post-application 4990 dermal contact with treated surfaces while participating in typical activities. 4991 6. Data are required for residential use site s, schools, and daycare institutions. This 4992 includes but is not limited to the following: Residential and public access premises; material 4993 preservatives (including those used in residential products, including but not limited to clothing 4994 and plastic toys) and wood preservatives (when contac t with treated wood is likely to occur). 4995 7. Data are required for occupational and residential uses if the human activity data 4996 indicate the potential for post-application dermal and/or inhalation exposures while participating in 4997 typical activities and no acceptable modeling options are available. 4998 8. Biological monitoring data may be submitted in addition to, or in lieu of, dermal and 4999 inhalation passive dosimetry exposure data pr ovided the human pharmacokinetics of the 5000 pesticide or metabolite/analog compounds ( i.e. , whichever method is selected as an indicator of 5001 body burden or internal dose) allow for a back- calculation to the total internal dose. 5002 9. Data are required for occupational and re sidential uses if there is the potential for 5003 bystander exposure and the pesticide use could result in respirable and/or inhalable material 5004 (e.g., gas, vapor, aerosol, or particulates). 5005 10. Data reporting and calculations are r equired only if post-application exposure data 5006 are required. 5007 §158.2280 Environmental fate. 5008 (a) General. Subpart B of this part and § 158.2201 describe how to use 5009 the table in paragraph (c) of this secti on to determine the environmental fate data 5010 requirements for antimicrobial pestici de products. Notes that apply to an 5011 individual test including specific condition s, qualifications, or exceptions are listed 5012 in paragraph (d) of this section. 5013 (1) Environmental fate data are requir ed to support the registrations of all 5014 end-use and manufacturing-use antimicrobial products. 5015*** Deliberative Internal Document – Do NOT Cite, Quote, or Release *** 222 (2) Data on transformation/degradation products or leachate residues of 5016 the parent compound are al so required to support registration, if the 5017 transformation/degradation/leachate products meet one of the following criteria: 5018 (i) More toxic, persistent, or bioaccumulative than the parent; 5019 (ii) Have been shown to cause adver se effects in mammalian or aquatic 5020 reproductive studies; or 5021 (iii) The moiety of concern (i.e., functional group in the parent chemical 5022 molecule that imparts adverse effects) remains intact. 5023 (3) For the purpose of determining dat a requirements, the “All Other” use 5024 patterns category includes t he following use patterns: 5025 (i) Agricultural premises and equipment. 5026 (ii) Food-handling/stor age establishments, premises, and equipment. 5027 (iii) Commercial, institutional a nd industrial premises and equipment. 5028 (iv) Residential and public access premises. 5029 (v) Medical premises and equipment. 5030 (vi) Human drinking water systems. 5031 (vii) Materials preservatives. 5032 (viii) Swimming pools. 5033 (b) Key

. MP = Manufacturing use product; EP = End-use product; R = 5034 Required; CR = Condit ionally required; NR = Not r equired; TGAI = Technical 5035 grade of the active ingredient; TEP = Typical end-use product; PAIRA = Pure 5036 active ingredient radiolabeled; ROC = residue of concern. 5037 5038(c)Table.The following table shows the data requirements forenvironmental fate. The test notes appear in5039paragraph (d) of this section.5040Table -- Antimicrobial Environmental Fate Data Requirements5041GuidelineNumberDataRequirementUse Pattern Test Substance TestNoteNo.IndustrialProcessesand WaterSystemsAntifoulantCoatings andPaintsWoodPreservativesAquaticAreasAllOtherUsePatternsCategoryMP EPDegradation Studies – Laboratory835.2120Hydrolysis R R R R R TGAI orPAIRATGAI orPAIRA1835.2240Photodegradation in waterR R R R R TGAI orPAIRATGAI orPAIRA2835.2410Photodegradation in soilNR NR R NR NR TGAI orPAIRATGAI orPAIRA10Toxicity and Fate in Wastewater Systems850.6800OECD209ActivatedSludge,RespirationInhibition TestR R R NR R TGAI TGAI835.1110ActivatedSludgeSorptionIsothermCR CR CR NR CRTGAI TGAI 19,20835.311 Ready CR CR CR NRCR TGAI TGAI 3, 4,*** Deliberative Internal Document – DoNOT Cite, Quote, or Release ***2240 Biodegradability18835.3220Porous PotStudyCR CR CR NR CRTGAI TGAI 3, 18835.3280SimulationTests to AssesstheBiodegradability of ChemicalsDischarged inWastewaterCR CR CR NR CRTGAI TGAI 3, 18835.3240Simulation Test– AerobicSewageTreatment: A.ActivatedSludge UnitsCR CR CR NR CRTGAI TGAI 3, 18Mobility Studies835.1230835.1240Leaching andadsorption/desorptionR R R R CR TGAI orPAIRATGAI orPAIRA5, 6Metabolism Studies – Laboratory835.4100Aerobic soilmetabolismCR NR R CR CR TGAI orPAIRATGAI orPAIRA7, 8,9835.4200Anaerobic soilmetabolismNR NR R NR CR TGAI orPAIRATGAI orPAIRA5, 8835.430 Aerobic aquatic R R R R CRTGAI or TGAI or 5, 8*** Deliberative Internal Document – DoNOT Cite, Quote, or Release ***2250 metabolism PAIRA PAIRA835.4400AnaerobicaquaticmetabolismR R R R CR TGAI orPAIRATGAI orPAIRA5, 8Dissipation Studies – Field835.6200Aquatic(sediment)CR R CR R CR TEP TEP 11,12,13Ground and Surface Water MonitoringNone Monitoring ofrepresentativeU.S. watersCR CR CR CRCR ROC ROC 11,14,17Special StudiesNone SpecialleachingNR R R NR NR TGAI TEP 15,16226

226 (d) Test notes. The following test notes appl y to the data requirements in 5042 the table in paragraph (c) of this section: 5043 1. For testing antifoulant paints and coatings , testing is to be performed separately with 5044 both sterile buffered distilled water and sterile sy nthetic seawater at pHs 5, 7, and 9. 5045 2. Not required if: 5046 (i) The electronic absorption spectra, measur ed at pHs 5, 7 and 9, of the chemical and 5047 its hydrolytic products, if any, show no absorpt ion or tailing between 290 and 800 nm, inclusive; 5048 or 5049 (ii) The results of the hydrolysis study at all three pHs (5, 7, and 9) demonstrates a half5050 life of less than 30 days. 5051 3. The results of the activated sludge, resp iration inhibition (ASRI) test determine which 5052 of the following tests are required: Ready biodegradability, porous pot, the biodegradation in 5053 activated sludge study as descri bed in the “Simulation Tests to Assess the Biod egradability of 5054 Chemicals Discharged in Wastewat er,” or simulation test – aerobic sewage treatment: A. 5055 activated sludge units. 5056 (i). If the ASRI test EC 50 is equal to or less than 20 mg/L, then the applicant must choose 5057 either to: 5058 (A). Conduct the biodegradation in activated sludge study as described in the “Simulation 5059 Tests to Assess the Bi odegradability of C hemicals Discharged in Wastewater”; 5060 (B). Conduct the porous pot test; or 5061 (C). Conduct the simulation test – aerobic se wage treatment: A. activated sludge units. 5062 (ii). If the ASRI test EC 50 is greater than 20 mg/L, then the applicant must choose either 5063 to: 5064 (A). Conduct a ready biodegradability study; or 5065 (B). Conduct one of the following studies: The biodegradation in activated sludge study 5066 as described in the “Simulation Tests to Asse ss the Biodegradability of Chemicals Discharged in 5067 Wastewater,” the porous pot test, or the simulati on test – aerobic sewage treatment: A. activated 5068 sludge units. 5069 4. Pass criteria for the ready biodegradab ility study are: 70% removal of dissolved 5070 organic carbon (DOC) and 60% removal of theor etical oxygen demand (ThOD) or theoretical 5071 carbon dioxide (ThCO 2 ) production for respirometric methods. These pass levels must be 5072 reached in a 10-day window within the 28-day period of the test. If the antimicrobial passes the 5073 ready biodegradability study, then no further testing is required. If the antimicrobial fails the ready 5074 biodegradability study, then the applicant must conduct one of the following studies: The 5075 biodegradation in activated sludge study as desc ribed in the “Simulation Tests to Assess the 5076 Biodegradability of Chemicals Discharged in Wastew ater,” the porous pot test, or the simulation 5077 test – aerobic sewage treatment: A. activated sludge units. 5078 5. For the all other use patterns category (as specified in § 158.2280(a)(3)), data are 5079 required based on a weight-of-evidence eval uation of the results of the hydrolysis, 5080 photodegradation in water, activated sludge sorp tion isotherm, biodegradability, and activated 5081 sludge, respiration inhibition tests. 5082 6. Adsorption and desorption using a batch equilibrium method is preferred. In some 5083 cases, as when the antimicrobial pesticide degrades rapidly, soil column leaching with unaged or 5084 aged columns may be more appropriate to fully char acterize the potential mobility of the parent 5085 compound and major transformation products. 5086 7. For industrial processes and water sys tems, aquatic areas, and the all other use 5087 patterns category (as specified in § 158.2280(a)(3)), data are required based on a weight-of5088 evidence evaluation of the result s of the hydrolysis, photodegradation in water, activated sludge 5089 sorption isotherm, biodegradability, and activa ted sludge, respiration inhibition tests. 5090 8. The environmental media (soil, water, hydrosoil, and biota) to be utilized in these 5091 studies must be collected from areas representative of potential use sites. 5092 9. For industrial processes and water sys tems, and aquatic areas, data are required for 5093 use sites that are intermittently dry. 5094227

227 10. For non-metallic antimicrobials, data are not required if the standardized soil profiles 5095 demonstrate that the antimicrobial is likely to readily degrade either microbially or via redox 5096 reactions (chemically). 5097 11. Analytical methods used to generate dat a associated with this study must include 5098 results of a successful confirmatory method trial by an independent laboratory. 5099 12. Protocols must be approved by the Agen cy prior to the initiation of the study. 5100 13. For industrial processes and water sys tems, wood preservatives, and the all other 5101 use patterns category (as specified in § 158.2280( a)(3)), data are required based on the potential 5102 for aquatic exposure and if the weig ht-of-evidence indicates that t he active ingredient or principal 5103 transformation products are likely to have the pot ential for persistence, mobility, nontarget aquatic 5104 toxicity, or bioaccumulation. 5105 14. Data are required if the weight-of-evi dence indicates that the active ingredient or 5106 principal transformation products ar e likely to occur in nontarget freshwater, estuarine, or marine 5107 waters such that human or environmental expos ures are likely to occur. In making that 5108 determination, the Agency takes into account other fa ctors such as the toxicity of the chemical(s), 5109 available monitoring data and the vulnerability of the freshwater, estuarine, or marine water 5110 resources in the antimicrobial use area. 5111 15. For wood preservatives, an aquatic l eaching study is required. A soil leaching study 5112 is required if human or environmental exposures are likely to occur from leachates that contain 5113 the active ingredient or principal transformation products from wood treated with a preservative 5114 product. Protocols must be approved by the Agenc y prior to the initiation of the study. 5115 16. For antifoulant paints and coatings, a l eaching study is required. Protocols must be 5116 approved by the Agency prior to the initiation of the study. 5117 17. Protocols, which include the residues of concern (such as parent, 5118 degradate/transformation product, and/or leachate re sidues) that would be monitored, must be 5119 approved by the Agency prior to the initiation of the study. 5120 18. A biodegradation study is not required if the antimicrobial meets one or more of the 5121 following criteria: 5122 i. Classified as a metal; 5123 ii. Relatively volatile, but not hydrophobic; 5124 iii. Highly reactive. 5125 19. The Activated Sludge Sorption Isotherm test is not required if the antimicrobial is: 5126 i. Relatively volatile, but not hydrophobic; 5127 ii. Highly reactive; or 5128 iii. The log K ow is less than 3.0. 5129 20. If the criteria of test note (19) of this paragraph are not met, then the Activated 5130 Sludge Sorption Isotherm test is required if one or more of the following criteria are met: 5131 i. The antimicrobial is a metal. 5132 ii. The log K ow is greater than or equal to 3.0. 5133 iii. The antimicrobial is posi tively charged or polycationic. 5134
iv. The EC 50 in the activated sludge, respiration inhi bition test is less than or equal to 20 5135 mg/L. 5136
v. The EC 50 in the activated sludge, respiration inhibition test is greater than 20 mg/L, 5137 and the antimicrobial fails the ready biodegradability study. 5138 5139 § 158.2290 Residue Chemistry 5140228

228 (a) General . Subpart B of this part and §158.2201 describe how to use 5141 the table in paragraph (h) of this secti on to determine the residue chemistry data 5142 requirements for antimicrobial pesticide products. Notes that apply to an 5143 individual test including specific condition s, qualifications, or exceptions are listed 5144 in paragraph (i) of this section. 5145 (b) Residue chemistry data are required for: 5146 (1) Antimicrobial end-use products with uses that may result in residues in 5147 or on food including, but not limited to: 5148 (i) Products that require a tolerance, tolerance exemption, or food additive 5149 regulation or clearance. 5150 (ii) Products that may be used to tr eat livestock or poultry drinking water, 5151 for food egg washing, or fo r fruit and vegetable rinses. 5152 (iii) Products that may be applied to a surface or incorporated into a 5153 material that may contact food or feed. Data are required r egardless of whether 5154 the antimicrobial is ap plied or impregnated for t he purpose of imparting 5155 antimicrobial protection to external surfaces of the substance or article, or for the 5156 purpose of protecting the substance or article itself. 5157 (iv) Products that may be applied to wa ter that have the potential to result 5158 in residues in potable water, or in water used for livestock and poultry drinking 5159 water, irrigation of crops, or water c ontaining fish that may be used for human 5160 food. 5161229

229 (v) Wood preservative or antif oulant products intended for treating 5162 submerged materials that may result in food contact (e.g., lobster pots, fish 5163 cages on fish farms). 5164 (2) Each manufacturing-use product bear ing directions fo r formulation into 5165 an end-use product bearing uses described in paragraph (b)(1) of this section. 5166 (c) Residue chemistr y data are not required under paragraph (b) of this 5167 section if no adverse effects (no toxici ty endpoints) are asso ciated with dietary 5168 exposure to the active ingr edient or if theoretical (h igh-end) dietary exposure 5169 estimates combined with the applicable toxicity endpoint result in acute and 5170 chronic dietary risks that are below the Agency levels of concern. 5171 (d) For purposes of this section, Magnitude of the Residue Studies 5172 include the following: Food-handling, mi gration studies, potable water, fish, 5173 irrigated crops, meat/milk/poultry/eggs, crop field trails, processed food or feed, 5174 and anticipated residues. 5175 (e) If the antimicrobial chemical ma y be applied to a field crop, then the 5176 residue chemistry data requirements of § 158.1410 apply. 5177 (f) The following term is defined fo r the purposes of this section: 5178 Residue of concern means the parent pesticidal compound and its metabolites, 5179 degradates, and impurities of toxicological concern. 5180 (g) Key. R = Required; CR = Conditionally required; NR = Not required; 5181 TGAI = Technical grade of the active i ngredient; TEP = Typical end-use product; 5182 PAI = Pure active ingredient; PAIRA = Pure active ingredient radiolabeled; ROC 5183 = Residue of concern. 5184230230(h)Table.The following table shows the data requirements for residue chemistry. The test notes appear in5185paragraph (i) of this section.5186Table -- Antimicrobial ResidueChemistry Data Requirements5187GuidelineNumberData Requirement Uses TestSubstanceTest NoteNo.AgriculturalPremiseIndirectFoodDirect Food AquaticSupporting Information860.1100 Chemical identity R R R R TGAI --860.1200 Directions for use R R R R -- --860.1550 Proposedtolerance/tolerance exemptionRRRR--1860.1560 Reasonablegrounds in supportof petitionRRRR--1860.1650 Submittal ofanalyticalreferencestandardsRRRRPAI/ROC2Food-Contact Surfaces Or Impregnated Materials860.1460 Food-handling CRCR CR CR TEP 3231231NoneNature of residueon surfacesCRCRCRCRPAIRA orTGAI4None Migration studiesCR CR CR CR TEP 5860.1340Residue analyticalmethod for datacollectionCRCRCRCRROC6860.1380 Storage stability R R R R TEP orROC7Higher tiered860.1300Nature of theresidue in plantsCRCRCRCRPAIRA8860.1300Nature of theresidue in livestockCRCRCRCRPAIRA9860.1340Residue analyticalmethods fortolerance/tolerance exemptionenforcementCRCRCRCRROC10860.1360 Multiresiduemethod testingCR CR CR CR ROC 11860.1400 Potable water CRCR CR CR TEP 12860.1400 Fish CR CRCR CR TEP 13860.1400 Irrigated crops CRCR CR CR TEP 14860.1480 Meat/milk/poultry/eggsCR CR CR CR TGAI orROC15860.1500 Crop field trialsCR CR CR CR TEP 16860.1520 Processed food orfeedCR CR CR CR TEP 17None Anticipated CR CR CR CR ROC 18232232residues5188518951905191 5192 5193 (i) Test notes. The following test notes appl y to the data requirements in 5194 the table to paragraph (h) of this section: 5195 1. A petition proposing a numerical toleranc e or a tolerance exemption is required for 5196 any food or feed use subject to section 408 of FF DCA if the use is not covered by an existing 5197 tolerance or tolerance exemption. If the use is subject to FFDCA section 409, the applicant must 5198 identify to EPA an applicable section 409 food additive regulation or clearance, or submit a copy 5199 of a petition to FDA requesting a section 409 food add itive regulation or clearance for the food or 5200 feed use. 5201 2. An analytical reference standard is required for any food or feed use requiring a 5202 numeric tolerance or exemption. Material safety data sheets as specified by Occupational Safety 5203 and Health Administration in 29 CFR 1910.120 0 must accompany analytical standards. 5204 3. Data are required if a pesticide may be used in a food-handling establishment unless 5205 data including, but not limited to, theoretical (high- end) estimates, radiolabeled laboratory data, or 5206 the nature of the residue on surfaces study show that residues will not occur in food or feed. 5207 4. If an antimicrobial pesticide may be app lied to a food-contact surface or impregnated 5208 into a food-contact material and if theoretical (high-end) estimates of exposure exceed EPA’s risk 5209 level of concern, then the nature of the residue on surfaces study is requi red. Protocols must be 5210 approved by the Agency prior to the initiation of the study. 5211 5. Based on the results of the nature of t he residue on surfaces study, if residues of 5212 concern are identified, then the migration study will be required. Protocols must be approved by 5213 the Agency prior to the initiation of the study. 5214 6. If a magnitude of the residue study, as specified in §158.2290(d), is required, then a 5215 residue analytical method suitable for collecting data is also required. The method must be 5216 capable of determining all residues of concern, to permit calculation of dietary risk or to establish 5217 a tolerance or tolerance exemption. 5218 7. If a magnitude of the residue study, as specified in §158.2290(d), is required, then 5219 storage stability data are also required, unless anal ytical samples are stored for 30 days or less. 5220 If, during hazard characterization, a residue has been identified as “of concern” and is known to 5221 be volatile or labile, then storage stability data are required regardless of sample storage time. 5222 8. If crop plants or metabo lically active raw agricultural commodities of food crops may 5223 be directly or indirectly exposed to an antimicr obial, plant metabolism studies are required to 5224 determine the transformation products that may enter the human diet. Such exposure could 5225 include, but is not limited to: 5226 i. Treatment of storage or shipping containers, 5227 ii. Postharvest fruit and vegetable treatment prior to shipping or storage, 5228 iii. Use of antimicrobial-tre ated water for irrigation, and 5229 iv. Any direct food contact use. 5230 9. If livestock may be exposed to an antimicrobial, then hen and ruminant metabolism 5231 studies are required to determine the identities of residues of concern that may enter the human 5232 diet from consumption of livestock commodities . Livestock may be exposed via the oral, dermal, 5233 or inhalation route following treatment or cont amination of sites including, but not limited to, 5234 livestock premises, feed, and drinking water. S hell eggs and other metabolically active livestock 5235 products may also be treated. If livestock may be exposed to one or more residues of concern 5236 differing from those found in animals, then one or more additional livestock metabolism studies 5237 involving dosing with these residues may be required. 5238234

234 10. If there is a numerical tolerance or tolerance exemption level to enforce, then a 5239 residue analytical method suitable for enforcemen t purposes is required. The method must be 5240 supported by an independent laboratory validation. 5241 11. If there is a numerical tolerance or tole rance exemption level to enforce, then testing 5242 is required to determine whether the Food and Dr ug Administration/United States Department of 5243 Agriculture multiresidue methodology would detect and identify the antimicrobial and its residues 5244 of concern, as part of programs to moni tor pesticides in the U.S. food supply. 5245 12. Data are required if an antimicrobial may be applied directly to water or if there is the 5246 potential that the antimicrobial-tr eated water could be used directly for drinking water purposes by 5247 humans or animals or that contam inated water could run-off, leach, or be discharged from treated 5248 sites or materials and make its way into potable water. 5249 13. Data are required if an antimicrobial may be applied directly to water inhabited by 5250 fish or that will be inhabited by fish or if cont aminated water could run-o ff, leach, or be discharged 5251 from treated sites or materials and make its way into bodies of water containing fish that may be 5252 used for human consumption. 5253 14. Data are required if an antimicrobial may be applied directly to water used for 5254 irrigation of food crops or such that contaminated water could r un-off, leach, or be discharged 5255 from treated sites or materials to make its way into water used for irrigation of food crops. 5256 15. If the antimicrobial may be applied directly to livestock, metabolic ally-active livestock 5257 commodities (e.g., eggs), livestock feed or drinking water, or livestock pr emises, or a livestock 5258 metabolism study indicates that residues of the ant imicrobial may result in livestock commodities, 5259 studies are required to determine the magnitude of th e residues of concern in fat, meat, meat by5260 products, milk, poultry, and eggs that may be consumed by humans. These studies, however, 5261 may not be required in cases where the livestock metabolism studies indicate that transfer of 5262 pesticide residues of concern to tissues, milk, and eggs is not expected to occur at the maximum 5263 expected exposure level for the animals. 5264 16. If food crops or raw agricultural co mmodities of food crops may be exposed to an 5265 antimicrobial, then residue studies are required to determine the magnitude of the residues of 5266 concern that may enter the human diet. Such exposures include, but are not limited to, 5267 postharvest fruit and vegetable treatments and applic ation of antimicrobial chemicals to field 5268 crops, mushroom houses, empty or occupied b eehives, or wood used to construct beehives. 5269 17. Data on the nature and magnitude of resi dues in processed food or feed are required 5270 if antimicrobial residues could pot entially concentrate on processing. If so, the establishment of a 5271 separate tolerance higher than that in the raw agricultural commodity may be required. 5272 18. Data are required when dietary exposure values at the tolerance level or screening5273 level (high-end) result in estima tes of dietary or aggregate risk that meet or exceed the Agency’s 5274 level of concern. These data may include, but ar e not limited to, washing, cooking, processing, or 5275 degradation studies as well as market basket surv eys for a more realistic residue determination. 5276 Protocols must be approved by the Agency pr ior to the initiation of the study. 5277 5278 5279 PART 161—[AMENDED] 5280 5281 7. The authority citation for part 161 continues to read as follows: 5282 Authority: 7 U.S.C. 136 – 136y. 5283 5284 Part 161 [Removed] 5285 5286 8. Part 161 is removed: 5287