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Page 1 of 233 EO12866_RIN_2070-AD30_Part 158W-FRM_2012-11-29.docx 1 EO 12866_Antimicrobial Data Requireme nts_RIN 2070 - AD30_FRM_2011 - 09 - 19 .docx 2
Draft document submitted as revised during Interagency review. 3 BILLING CODE 6560–50–P 4 ENVIRONMENTAL PROTECTION AGENCY 5 40 CFR Part s 158 and 161 6 [ EPA–HQ–OPP–2008–0110; FRL– XXXX
– X 8886–5] 7 RIN 2070–AD30 8 Data Requirements for Antimicrobial Pesticides 9 AGENCY: Environmental Protection Agency (EPA). 10 ACTION: Final rule. 11 SUMMARY: EPA is revising and updating the data requirements for antimicrobial 12 pesticide products , which to reflect current scientif ic and regulatory practices

. Besides 13 providing , and to provide the regulated community with clearer and more transparent 14 information , about the data needed to support pesti cide registration decisions for 15 antimicrobial products. The updated data requirements also serve to further enhance 16 EPA’s ability to make regul atory decisions about the hum an health, and environmental 17 fate and effects of antimicrobial pesticide products. These revisions are also expected 18 to help protect human health and the environment by provid ing an up-to-date scientific 19 framework for identifying and assessing the risks of antimicrobial pesticides sold or 20 distributed in the United States. 21 DATES: This final rule is effective [ insert date 60 days after date of publication in the 22 Federal Register ]. 23 ADDRESSES: EPA has established a The docket for this action , identified under docket 24 identification (ID) number EPA–HQ–OPP–2008–0110 . All documents in the docket are 25*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 2 of 233 listed in the docket index , is available at http://www.regulations.gov . Although listed in 26 the index, some information is not publicly available, e.g., Confidential Business 27 Information (CBI) or other information whose disclosure is restricted by statute. Certain 28 other material, such as copyri ghted material, is not placed on the Internet and will be 29 publicly available only in hard copy form . Publicly available docket materials are 30 available in the electronic docket at http://www.regulations.gov , or, if only available in 31 hard copy, at the OPP Regulatory Public Docket in Rm. S

– 4400, One Potomac Yard 32 (South the Environmental Protection Agency Do cket Center (EPA/DC), located in the 33 EPA West Bldg .), 2777 S. Crystal Dr., Arlington, VA. The Docket Facility ., Rm. 3334, 34 1301 Constitution Ave., NW., Washington, DC 20460-0001. The Public Reading Room 35 is open from 8:30 a.m. to 4 :30 p.m., Monday through Friday, excluding legal holidays. 36 The Docket Facility telephone number for the Public Reading Room is (202) 566-1744, 37 and the telephone number for the OPP Docket is (703) 305

– - 5805. Please review the 38 visitor instructions and additional in formation about the docket available at 39 http://www.epa.gov/dockets

. 40 FOR FURTHER INFORMATION CONTACT: Kathryn Boyle, Field and External Affairs 41 Division (7506P), Office of Pesticide Program s, Environmental Protection Agency, 1200 42 Pennsylvania Ave., NW., Washington, DC 20460–0001; telephone number: (703) 305- 43 6304; e-mail address: boyle.kathryn@epa.gov , or contact Scott Drewes, same address; 44 telephone number (703) 347- 0107; email address: drewes.scott@epa.gov

. 45 SUPPLEMENTARY INFORMATION: 46 I. General Information Executive Summary 47 A. Does this Action Apply to Me? 48 You may be affected by this action if y ou are a producer of pesticide products 49 (NAICS 32532), antifoulants (NAI CS 32551), antimicrobial pes ticides (NAICS 32561) or 50*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 3 of 233 wood preservatives (NAICS 32519), importers of such products, or any person or 51 company who seeks to register an antimic robial, antifoulant coating, ballast water 52 treatment, or wood preservative pesticide or to obtain a tolerance for such a pesticide. 53 The North American Industrial Classifi cation System (NAICS) codes have been 54 provided to assist you and ot hers in determining whether this action might apply to 55 certain entities. This listing is not intended to be exhaus tive, but rather provides a guide 56 for readers regarding entities likely to be affect ed by this action. Ot her types of entities 57 not listed above could also be affected. could also be affected. The North American 58 Industrial Classification System (NAICS ) codes have been provided to assist y ou and 59 others in determining whether this acti on might apply to certain entities. If you have any 60 questions regarding the applicability of this ac tion to a particular entity, please contact 61 Nader Elkassabany, Chief of the Risk Asse ssment and Science Support Branch in the 62 Antimicrobials Division of t he Office of Pesticide Programs at ( 703 ) 308

- 8783 or via 63 email,

. 64 B . What is the Agency's Author ity for Taking this Action? 65 B. How Can I Access Electronic Copies of this Document? 66 67 In addition to accessing an electronic copy of this Federal Register document through the 68
electronic docket at http:// www.regulations.gov , you may access this Federal Register document 69 electronically through the EPA Internet under the ‘‘ Federal Register ’’ listings at 70 http://www.epa.gov/fedrgstr . You may also access a frequently updated electronic version of 40 CFR 71 parts 158 and 161 through the Government Printing Office’s pilot e

- CFR site at http:// 72 www.gpoaccess.gov/ecfr

. To access the harmonized test guidelines referenced in this document 73
ele ctronically, please go to and select “Test Methods and Guidelines.” 74 II. Background 75 A. This action is issued under the authority of sections 2, 3, 4, 5, 10, 12, and 25 of 76 the Federal Insecticide, Fungi cide and Rodenticide Act (FIF RA), 7 U.S.C. 136 et seq., 77*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 4 of 233 and section 408 of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 78 346a. The data required for antimicrobials (e .g., for registration, reregistration or 79 registration review, experimental use permit (E UP), or tolerance/to lerance exemption) 80 are currently listed in 40 CFR part 161 and, wit h this final rule, will be listed in 40 CFR 81 part 158. 82 C. What Action is the Agency Taking? 83 The Environmental Protection The Agency ( EPA or the Agency) is revising and 84 updating the data requirements fo r antimicrobial pesticides that are currently found in 85 Title 40 of the Code of Federal Regulations (CFR) in part 161, and which are being 86 relocated as revised by this rule to subpart W of part 158. Subpart W sets out data 87 requirements specific to antimicrobial produc ts that are described by the antimicrobial 88 use patterns and use exposure considerations particular to antimicrobials. With the 89 promulgation of part 158, subpart W, EPA is removing part 161, entitled “Data 90 Requirements for Registration of Antimicrobial Pesticides” as it is no longer needed. 91 Antimicrobial pesticides are used to cont rol microbiological contamination in 92 healthcare applications, and deterioration in industrial, commercial, and consumer 93 products. Nearly 60 percent of antimicrobial products are registered as public health 94 products (as defined at FIFRA 2(gg)) to contro l infectious microorganisms in hospitals 95 and other health care environments. Public health products are intended to control 96 microorganisms infectious to humans in any inanimate environment. The common 97 public health antimicrobial products include ster ilants, disinfectants, and sanitizers. 98 Nonpublic health products are sold and distri buted for use to control growth of algae, 99 odor-causing bacteria, bacteria which cause spoilage, deteriorati on or fouling of 100 materials and microorganisms infectious only to animals. Other examples of nonpublic 101 health products include products used in coo ling towers, jet fuel, paints, and treatments 102*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 5 of 233 for textile and paper products

. Within this final rule EPA is using the term antimicrobials 103 to collectively refer to antim icrobial pesticides, antifoulant coatings and paints, and wood 104 preservatives. The amendments contained in this final rule, which are discussed in 105 detail in Units IV. through XXII. of this document, change the existing data requirements 106 for antimicrobial pesticides in t he following substantive respects: 107

 By changing some of the existing data requirements, such as a change from 108 conditionally-required to required, a change in the number of test s pecies, or expanding 109 the number of use patterns for which the test is required. 110

 By adding newly codified data requirements, i.e., data requirements that are not 111 currently identified in 40 CFR part 161, but ar e considered in current practice on a case112 by-case basis. 113

 By adding new data requirements, i.e., data requirements that have not been 114 required or have rarely been required in curre nt practice on a case-by-case basis, and 115 have not been routinely considered during the Agency’s evaluation of the data needed 116 for the purpose of risk assessment. 117

 By eliminating the requirement for the chronic non-rodent study currently 118 required in 40 CFR part 161. 119

 By codifying the antimicrobial data requirements as finalized in this rule in 40 120 CFR part 158, subpart W, and removing the current requirements that appear in 40 121 CFR part 161. 122 D. What are the Incremental Cost s and Benefits of this Action? 123 The Economic Analysis (EA) of the pot ential costs and benefits associated with 124 this action, as revised to address comments received on the proposed rule, is contained 125 in a document entitled “Final Economic A nalysis of Changes in Data Requirements for 126*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 6 of 233 Antimicrobial Pesticides” (Ref. 1), a copy of which is in the docket, discussed in Unit 127 XXII., and are briefly summarized here. 128 1. Estimated costs. In its analysis, the Agen cy considered the potential, 129 additional costs for the registration of new antimicrobial pesticides or new uses of 130 currently registered antimicr obial pesticides, as well as the potential, additional costs 131 incurred during the registration review of existing antimicrobial pesticides. 132 The estimated total annual industry costs of the final rule is expected to be about 133 $19.3 million. The difference between the baseline costs (the existing data 134 requirements that were codified in 1984) and t he cost of the Agency’s current practices 135 is about $1 million annually. The differenc e between the baseline costs and the final 136 rule costs, i.e., the incremental costs, is approximately $8.2 million annually assuming 137 an estimated 15 new registrations. 138 Under the final rule, the average cost per registration action of a new 139 antimicrobial active ingredient is approximately $1 million to $5 million. For existing 140 chemicals, data requirements in part 158, s ubpart W are relevant to the registration 141 review program, and the average additional cost is estimated to be about $588,000 for 142 wood preservatives, $284,000 for food and i ndirect food uses, and $260,000 for all 143 other uses. For registration review , the total annual cost is $6.8 million. 144 EPA also conducted an analysis of the potenti al impact of this final rule on small 145 entities, which is included in the EA and di scussed in Unit XXV.C. In brief, EPA 146 estimates that 500, or approx imately 67 percent, of the uni que parent companies that 147 constitute the total universe of pesticide ant imicrobial registrant s, qualify as a small 148 business. When considering both registrati on review and new registrations, on average 149 each year about 30 small businesses are estima ted to incur additional costs under this 150 final rule. EPA estimates that about 23 sma ll firms (almost 5 percent of the 500 small 151*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 7 of 233 antimicrobial firms) may experie nce an economic impact of 3 percent or more of gross 152 sales, As discussed later in this docum ent, EPA has concluded based on this analysis 153 that this potential impact is not a significant impact on a substantial num ber of small 154 entities. 155 2. Estimated benefits. In its analysis, EPA provides a qualitative discussion of 156 the benefits, which are not quantif iable in the same monetary terms as the costs. In 157 general, before manufacturers can sell pes ticides in the United States, EPA must 158 evaluate the pesticides thoroughly to ensure that they meet federal safety standards in 159 FIFRA and FFDCA that were established to protect human health and the environment. 160 EPA grants a "registration" or license that permits a pesticide's distribution, sale, and 161 use only after the company meets the scient ific and regulatory requirements. In 162 evaluating a pesticide registration applicatio n, EPA assesses a wide variety of potential 163 human health and environmental effects associ ated with use of the product. Applicants, 164 or potential registrants, mu st generate or provide the scientific data necessary to 165 address the identity, compositi on, potential adverse effects, and environmental fate of 166 each pesticide. The information provided by the data requirements in this final rule allow 167 EPA to evaluate whether an antimicrobial pesticide meets the applicable statutory 168 standards. 169 Antimicrobials play an important role in public health and safety. While intended 170 to provide health benefits of pathogen control or removal and, in so me cases, safety 171 benefits of materials preservation, they also involve risks of potential efficacy failure and 172 exposure of hazards to humans and the env ironment. Therefore, the effectiveness and 173 proper use of an antimicrobial pesticide is determined by EPA based on its evaluation of 174 specific data that is provided as part of r egistration and registration review activities. 175*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 8 of 233 This final rule will enhance EPA’s abilit y to make sound regulatory decisions and 176 help prevent the registration of pesticide products that may hav e unreasonable adverse 177 effects on human health and t he environment. The Agency believes that having the 178 appropriate data ultimately leads to bette r risk management decisions, as well as 179 provides the following other benefits: 180

a. More refined assessments mean less unc ertainty and clearer understanding of 181 actual risks . For example, EPA's current applicat or/user exposure data base is not 182 comprehensive, especially regarding exposu res to pesticides in industrial and 183 residential settings. Codifying these data requi rements, many of which are currently 184 applied on a case-by-case basis, would allo w the Agency to conduct improved exposure 185 assessments for applicators/user s. This will benefit workers and consumers by allowing 186 EPA to make better informed regulatory decisi ons that are neither too stringent nor too 187 lenient. 188 b. Clarity and transparency to regula ted community means savings. The 189 enhanced clarity and transparency of the info rmation presented in part 158, subpart W 190 will reduce uncertainty for applicants in generat ing and submitting data that is necessary 191 for EPA to be able to make registration dec isions based on data-driven risk estimates 192 that use fewer conservative assumptions. Applicants may save time and money by 193 understanding which studies ar e needed to support the use of their product. Thus, the 194 antimicrobial industry will, al ong with other partners in the regulated community, attain a 195 better understanding of and can more efficiently participate in the pesticide registration 196 process. This should allo w products to enter the mark et earlier, thereby enabling 197 registration of safer pesticides sooner and potentially reducing risks, as well as 198 increasing profits. The cl arity derived from having data requirements specific to 199 antimicrobials may be especially important to small firms and new firms entering the 200*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 9 of 233 industry who may have less experience than t hose firms that routinely work with the 201 Agency. 202

c. EPA information assists other communities in assessing pesticide risks. 203 Scientific, environmental, and health communiti es find pesticide toxicity information 204 useful to respond to a variety of needs. For example, medica l professionals are 205 concerned about the health of patients expos ed to pesticides; poison control centers 206 make use of and distribute information on toxicity and treatment associated with 207 poisoning; and scientists use toxicity information to characterize the effects of pesticides 208 and to assess risks of pesticide exposure. Sim ilarly those responsible for protection of 209 nontarget wildlife need reli able information about pesticides and assurance that 210 pesticides do not pose an unreasonable threa t. These data requirements will help the 211 scientific, environmental, and hea lth communities by increas ing the breadth, quality, and 212 reliability of Agency regulatory decisions by improving their scientific underpinnings. 213 d. Better informed users mean informed risk-reduction choices. Better regulatory 214 decisions resulting from these data requirem ents also mean that the label will provide 215 better information on the use of the pesticide. A pesticide label is the user's direction for 216 using pesticides safely and effectively. It contains important information about where to 217 use, or not use, the product, health and sa fety information that should be read and 218 understood before using a pesticide product, and how to dispose of that product. This 219 benefits users by enhancing their ability to obt ain pesticide products appropriate to their 220 needs, and to use and dispose of products in a manner that is safe and environmentally 221 sound. 222

e. Recognizes the unique down-the-drain us es associated with antimicrobials

. 223 For antimicrobial chemicals that go down- the-drain and eventually reach a WWTP, EPA 224 intends to conduct an assessment of the potentia l impact of the antim icrobial chemical 225*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 10 of 233 on the micro-organisms in t he biological treatment pr ocesses of a WWTP and the 226 potential for the antimicrobial chemical to pass through the WWTP in the effluent. The 227 final rule will minimize costs to states and municipalities by ensuring that antimicrobial 228 pesticide products registered under FIFRA don’ t cause water quality problems or harm 229 treatment facilities. 230 f. A milestone towards the Agency’s vision for 21st Century Toxicology and new 231 integrated testing strategies. The Agency’s goal is to use 21 st Century science to 232 increase the efficiency and effectiveness of our assessment process. This rule is a 233 launching pad for that vision. 234 II. Background 235 A . Brief History of Pesticide Data Requirements 236 W ithin t his final rule EPA is using the term antimicrobials to collectively refer to 237 antimicrobial pesticides, antifoulant coat ings and paints, and wood preservatives. EPA’s 238 data requirements for pesticides were first published in 1984. Those data requirements 239 were primarily influenced by agricultural us es. Since then, new risk concerns have 240 been identified, and EPA’s statutory mandates for pesticide registration under FIFRA 241 and tolerance-setting under the FFDCA were amended in 1996 to require EPA to 242 update the scientific under pinnings of risk assessments. The Agency must now perform 243 more in-depth risk analyses, such as aggregate and cumulative risk assessments. 244 On October 26, 2007, EPA promulgat ed final rules updating the data 245 requirements for conventional pesticides (72 FR 60934), and biochemical pesticides 246 and microbial pesticides (72 FR 60988). The rule development process for part 158, 247 subpart W used the updated conventional pestici des data requirements as the starting 248 point while considering the case-by-case data requirement decisions made over the 249*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 11 of 233 years of registering antimi crobial pesticide products. The following four subparts in part 250 158, promulgated in 2007, also apply to ant imicrobial pesticides (see 40 CFR 158.1): 251

 Subpart A: General Provisions 252

 Subpart B: How to Use Data Tables 253

 Subpart C: Experimental Use Permits 254

 Subpart D: Product Chemistry 255 To provide continued regulatory coverage for antimicrobial pesticides until the 256 Agency could promulgate a final regulation for antimicrobial pesticides, the 2007 final 257 rule (72 FR 60251, October 24, 2007) (FRL 8116- 2) preserved the original part 158 data 258 requirements (promulgated in 1984) to apply to antimicrobial pesticides by 259 redesignating them as part 161, This final ru le finishes the promulgation of a final 260 regulation for antimicrobial pesticides. Acco rdingly, EPA is also revoking 40 CFR part 261 161. 262 B. How to Use the Data Tables 263 In establishing the data requirem ents in 1984, EPA adopted a step-wise 264 approach to assist the applicant in det ermining the data needed to support the 265 registration of a particular product. This approach, which is described in 40 CFR part 266 158, subpart B, involves the us e of “data tables” to facilit ate the identification of the 267 applicability of the data requirements. In essence, the data requirements illustrate the 268 questions the registrant will need to answer about the safety of the pesticide product 269 before the Agency can r egister it. Because of the variety of chemicals and use patterns, 270 and because EPA must retain flexibility to tailor data requirements as appropriate, only 271 qualitative descriptors are in the tables. Test notes provide more specific information on 272 the applicability of spec ific data requirements. 273*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 12 of 233 The table descriptors NR (not requir ed), R (required), and CR (conditionally 274 required) should be viewed as a general presentat ion, indicating the likelihood that the 275 data requirement applies. The use of R does not necessarily indicate that a study is 276 always required, but that it is more likely to be required than not. For example, if the 277 applicant wanted to apply his pesticide to apple s, then crop field trials would be required 278 almost always on apples. However, if the physi cal/chemical properties of the chemical 279 did not lend themselves to the test, su ch as performing an inha lation test with a 280 chemical that is a solid and has an extremel y low vapor pressure, then a waiver might 281 be granted. Generally test notes for R st udies discuss any particular circumstances 282 when the testing mi ght not be required. 283 The use of CR means a study is less likel y to be required. Triggers in the test 284 notes indicate the circumstances under which the Agency has learned through 285 experience that the information is needed. Although only an appr oximation, if 286 percentages were to be assigned to indica te the need for a particular study, then R 287 could be viewed as representi ng the submission of a study 50% to 100% of the time 288 and CR would be up to 50%. 289 Thus, NR, R, and CR are used for convenience to make the table format 290 feasible, but serve only as a general indication of the applicability of a data requirement. 291 In all cases, the test notes referred to in the table must be consulted to determine the 292 actual need for the data. 293 The table format includes a column heading entitled “Guideline,'' which refers to 294 the OCSPP Harmonized Test Guidelines. Guideline numbers are provided as 295 information/guidance to applicants. Thes e Guidelines set forth recommended 296 instructions and test methods for performi ng a study to generate the required data. 297 Since these are guidance doc uments, the applicant is not required to use these 298*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 13 of 233 Guidelines, but may instead seek to fulfill the data requirement by other appropriate 299 means such as alternative test methods, s ubmission of an article from open literature, 300 or use of modeling. The applic ant may submit a protocol of his own devising for the 301 Agency to review. However, the OCSPP Ha rmonized Guidelines have been developed 302 through a rigorous scientific process, includi ng extensive peer review by the FIFRA 303 Scientific Advisory Panel. Additionally, many of the Guidelines have been harmonized 304 internationally. As such, they represent the recommended approach to developing high305 quality data that should satisfy EPA' s data needs for risk assessment. 306 In addition, since it is not possible to su fficiently delineate all circumstances in 307 test notes, consultation with EPA is encouraged. Applicants are also encouraged to visit 308 the Agency's website at 309 http://www.epa.gov/pesticides/r egulating/data_requirements.htm

. 310 C. Efforts to Incorporate 21 st Century Science into Pesticide Decision Making 311 B

. What is the Agency's Author ity for Taking this Action? 312 This action is issued under the authority of sections 2, 3, 4, 5, 10, 12, and 25 of 313 the Federal Insecticide and Rodenticide Act ( FIFRA ) as amended and section 408 of 314 the Federal Food, Drug, and Cosmetic Act ( FFDCA ) . The data required for a 315 registration, reregistration, experimental use permit (EUP) , or tolerance /tolerance 316 exemption for antim icrobials are listed in 40 CFR part 158. 317 C. Next Steps after this Rulemaking 318 Over the next several years, EPA’s Offi ce of Pesticide Programs (OPP) is 319 committed to improving and transforming our the Agency’s approach to pesticide risk 320 management by enhancing our the Agency’s ability to use integrated approaches to 321 testing and assessment. Over the next 5 years, The Pesticide Program plans to 322 maximize use of existing data from simila r compounds, including information from new 323*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 14 of 233 in silico and in vitro predictive models and exposure modeling to target in vivo toxicity 324 testing that is needed to assess and m anage chemical risks appropriately. 325 Over the next decade, as experience is gained and as our the Agency’s 326 understanding of toxicity pathways incr eases, an enhanced integrated testing and 327 assessment approach will be impl emented for all pesticides. The approach will fully 328 integrate hazard and exposure information us ing advanced computer modeling of new 329 in vitro data and an understanding of toxicity pathways to better predict risks and to 330 determine what additional data are necessary to provide a sound basis to manage risks 331 of concern. Data from improved biomarke rs of exposure and biological outcomes from 332 population-based studies will be used to evaluat e the effectiveness of this new risk 333 assessment paradigm, to readily identify early effects in exposed populations, and to 334 improve the approach. 335 Current Agency scientific and regulatory prac tice provides the foundation for this 336 final rule. While current practice is still largely dependent on animal ( in vivo ) testing, this 337 rule is one milestone towards the Agen cy’s longer term vision for 21st Century 338 Toxicology and new integrated testing strategi es. OPP believes that certain classes of 339 chemicals, such as antimicrobial pesticides , provide an appropriate starting point for 340 OPP’s planned transformation. Many ant imicrobials have both pesticidal and non341 pesticidal uses. In addition, many antimicr obial products are regulated under multiple 342 jurisdictions. Thus, many antimicrobi al chemicals have been assessed by other 343 regulatory programs and agencies. The ready availability of published literature and 344 publicly-available assessments offer a unique opportunity for the a pplicant to use the 345 available information as a starting point for fulfilling data requirements, and, when 346 appropriate, to use com puter modeling and/or in-vitro data to supplement or fulfill data 347 requirements. For example, O PP established a voluntary pilot program for eye irritation 348*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 15 of 233 testing of certain antimicrobial pesticides using non–animal test methods. OPP will 349 continue to evaluate use of new in vitro and computer-based approaches in our OPP’s 350 hazard and risk assessment processes as t he technologies are sufficiently developed 351 and peer-reviewed. Certain t ools are already available or anticipated to become 352 available in the near term including, (Quantit ative) Structure-Activity-Relationship 353 (Q)SAR/expert systems and in vitro high through

- put screening technologies. 354 Furthermore, in conjunction with the International Life Sciences Institute (ILSI), OPP is 355 currently pursuing the development of an applic ation of the thresholds of toxicological 356 concern (TTC) concept to evaluate antimicrobi al pesticides. In co llaboration with OPP, 357 EPA’s Office of Research and Development is providing momentum for achieving the 358 vision of 21 st Century Toxicology by developi ng and evaluating new technologies in 359 molecular, cellular, and computational sci ences to supplement or replace more 360 traditional methods of data development. OPP believes that its goal of using 21 st 361 Century science in integrated approaches to testing and assessment is achievable with 362 strong scientific and stakeholder support thr ough a transparent process. As the 363 enhanced integrated testing and assessment approach matures, based on these 364 scientific advances, EPA may determine to update its data requirements to reflect 365 evolving program needs as specified in § 158.30(c). See Unit V.C. and Unit XVIII. of 366 the proposed rule for further discussion of EPA’s use of integrated approaches to 367 testing and assessment. 368 D. Acronyms Used in this Document 369 The acronyms used throughout this document have the following meaning: 370 ACGIH means the American Conference of Governmental and Industrial Hygenists 371 AD means EPA’s Antimicr obial Division in OPP 372 ARTCA means the Antimicrobial R egulation Technical Correction Act 373*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 16 of 233 ASRI means Activated Sludge, Respiration Inhibition Test 374 ASSI means Activated Sludge Sorption Isotherm 375 ASTM means the American S ociety for Testing and Materials 376 AWPA means the American Wood Protection Association , formerly American Wood 377 Preservatives Association 378 “CR” means conditionally required 379 CFR means the Code of Federal Regulations 380 CDC means the Centers for Disease Control and Prevention 381 COC means concentration of concern 382 CWA means the Clean Water Act 383 DCI means Data Call

- in 384 D

- t

- D means down the drain 385 EA means economic analysis 386 EDSP means Endocrine Disr upter Screening Program 387 E

- FAST means Exposure and Fate Assessment Screening Tool 388 EP means end

- use product 389 EPA or th e Agency means the United States Environmental Protection Agency 390 ESA means the Endangered Species Act 391 EU means the European Union 392 EUP means experimental use permit 393 FDA means the Food and Drug Administration 394 FIFRA means the Federal Insecticide, Fungicide an d Rodenticide Act 395 FFDCA means the Federal Food Drug and Cosmetic Act 396 FQPA means the Food Quality Protection Act 397 FWS means the United States Fish and Wildlife Service 398*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 17 of 233 HHS means the United States Departm ent of Health and Human Services 399 HSRB means the Human S tudies Review Board 400 ICR means Information Collection Request 401 ILSA means International Life Sciences Institute 402 K d means soil partition coefficient 403 K oc means soil organic carbon

- water coefficient 404 K o w means octanol

- water partition coefficient 405 MOR means magnit ude of the residue 406 mg/L means milligram s per liter 407 NAICS means the North American Industrial Classification System 408 NAS means the National Academy of Sciences 409 NMFS means the United States Na tional Marine Fisheries Service 410 NPDES means National Pollution Discharge Elimination System 411 NPRM means III. Public Comments on the Notice of Proposed Rulemaking 412 (NPRM) 413 “NR” means not required 414 OCSPP means EPA’s Office of Chemical Sa fety and Pollution Prevention, formerly 415 Office of Pollution Prevention and Toxics (OPPTS) 416 OECD means Organisation for Econo mic Cooperation and Development 417 OMB means Office of Management and Budget 418 OPP means EPA’s Office of Pesticide Programs 419 OPPT means EPA’s Office of Pollution Prevention and Toxics 420 OSHA means Occupational Safety and Health Administration 421 OW means EPA’s Office of Water 422 PPCP means pharmaceuticals and personal care products 423*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 18 of 233 PEL means permissible exposure limit 424 ppb means parts per billion 425 ppm means parts per million 426 PPE means personal protective equipment 427 PRA means the Paperwork Reduction Act 428 PRIA means the Pestic ide Registration Improvement Act 429 POTW means publicly owned treatment works 430 QSAR or (Q)SAR means quantitative structure

- activity

- relationships 431 “R” means required 432 RAC means raw agricultural commodity 433 RED means Reregistration Eligibility Decision Document 434 RFA means the Regulator y Flexibility Act 435 RfC means Reference Concentration 436 RfD means Reference Dose 437 ROC means residue of concern 438 RQ means risk quotient 439 SAP means the FIFRA Scientific Advisory Panel 440 SAR means structure

- activity

- relationships 441 SBREFA means the S mall Business Regulatory Enforcement Fairness Act 442 TGAI means technical grade active ingredient 443 TTC means threshold of toxicological concern 444 TEP means typical end

- use product 445 TLV means threshold limit value 446 WET means whole effluent testing 447 WOE means weight

- of

- evidence 448*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 19 of 233 WQC means Water Quality Criteria 449 WQS means Water Quality Standards 450 WWTP means wastewater treatment plant 451 USDA means United Stated De partment of Agriculture 452 III. History of th is Rulemaking 453 A. Background 454 EPA’s data requirements for pestici des were first published in 1984. Those data 455 requirements were primarily influenced by agricultural uses. Since then, new risk 456 concerns have been identified, and EPA’s statutory mandates for pesticide registration 457 under FIFRA and tolerance

- setting under the FFDCA were amended in 1996 Comments 458 Submitted to require EPA to update the scientific underpinnings of risk assessments. 459 The Agency must now perform more in

- depth risk analyses, such as aggregate and 460 cumulative risk assessments

. EPA 461 On October 26, 2007, EPA promulgated final r ules updating the data 462 requirements for conventional pesticides (72 FR 60934), and biochemical pesticides 463 and microbial pesticides (72 FR 60988). The rule development process for p art 158 , 464 subpart W used the updated conventional pesticide s data requirements as the starting 465 point while considering the case

- by

- case data requirement decisions made over the 466 years of registering antimi crobial pesticide products. F our of the other subparts in part 467 158, promulgated in 2007 , also appl y to antimicrobial pesticides (see 40 CFR 158.1)

. 468 Those four subparts are : 469

 Subpart A: General Provisions 470

 Subpart B: How to Use Data Tables 471

 Subpart C: Experimental Use Permits 472

 Subpart D: Product Chemistry 473*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 20 of 233 As part of promulgating those final ru les, on October 24, 2007, (72 FR 60251) 474 EPA preserved the original part 158 data requirements (promulgated in 1984) , by 475 redesignating them as part 161 , to provide continued regulatory coverage for 476 antimicrobial pesticides until the Agen cy could promulgate a final regulation for 477 antimicrobial pe sticides

. This final rule finishe s th e promulgation of a final regulation for 478 antimicrobial pesticides . Accordingly, EPA is also revoking part 161 today. 479 B . Discussion of the unit discusses, in general terms, the public comments received on 480 the NPRM that appeared in the Federal Register of October 8, 2008 Notice of 481 Proposed Rulemaking (NPRM) 482 EPA published an NPRM on October 8, 2008 , (73 FR 59382 ) proposing to 483 establish data requirements specific to t he registration of antimicrobial pesticide 484 products in 40 CFR part 158 , subpart W. The clos ing date of the 90

– day ), and EPA’s 485 responses to those comments. The comment period for the NPRM was extended from 486 January 6, 2009 . The co mment period was extended to April 6, 2009, to allow 487 stakeholders additional time to assess the impact of the pr oposed revisions on their 488 particular situations and submit their comments. In addition, EPA convened a public 489 workshop in Arlington, Virginia, to explain th e provisions of the NPRM on November 6, 490 2008. The proposed rule, the notice of the ex tension of the comment period, the notice 491 of the public meeting, the presentations used at the public meeting, the comments 492 submitted, and EPA’s Response to Comments Document are available to in the public at 493 http://www. regulations.gov (see docket EPA

- HQ

- OPP

– 2008

– 0110 )

. for this rule. 494 C. Comments Submitted to EPA

. 495 During the public comment period, EPA re ceived comments on the proposed part 496 158, subpart W regulations from 29 entities. The breakdown of the origin of the 497 comments is as follows: 498*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 21 of 233  Antimicrob ial I ndustry

– 15 499

o Lanxess Corporation 500

o S.C. Johnson & Sons, Inc. 501

o Scientific and Regulato ry Consultants, Inc. 502

o Antimicrobial Exposure Joint Venture (AEJV) 503

o Consumer Specialty Products Association (CSPA) 504

o Ecolab Inc. 505

o ISSA 506

o The Clorox Company 507

o Reckitt Benckiser 508

o Mason Chemical Company 509

o Proctor & Gamble 510

o Dow Chemical Company 511

o Johnson Divers e y 512

o Troy Corporation 513

o American Chemistry Council (ACC) 514

 N o n - Governmental Organizations (N GOs )

– 3 515

o Env ironmental Working Group 516

o Humane Society 517

o Beyond Pesticides 518

 Other

– 3 519

o CropLife America 520

o Innovation and Reform Group 521

o Alternative Testing Working Group 522

 Foreign Government Entity

- 1 523*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 22 of 233 o Health Canada 524

 Water Agencies

– 7 525

o Hampton Roads Sanitation District 526

o California Association of Sanitation Agencies 527

o National Association of Clean Water Agencies 528

o San Francisco Department of the Environment 529

o Sanitation Districts of Los Angeles County 530

o Tri

- Tac 531

o C alifornia Stormwater Quality Association 532 There were also late comments from AC C, received at meetings held at EPA in 533 Arlington, VA on December 2, 2009, and June 14, 2010

. Most recently, , as well as at a 534 meeting on May 17, 2011, and in a letter dated June 17, 2011 , both ACC and CSPA 535 provided additional late comments . The presentation materials and EPA’s summary of 536 the meetings, and the letter with atta chments are included in the docket at 537 http://www.regulations.gov

. The . These late comments submitted by ACC and/or 538 CSPA were not new comments, but rather re-statements of issues presented in their 539 original comments submitted to EPA

. 540 A , and are also available in the docket. Another late comment cosigned by the 541 Physicians Committee for Responsible Medicine, the Humane Society International, and 542 People for the Ethical Treatment of Animals was submitted received on September 1, 543 2010

. This late comment did cont ain several new issues, which , that were addressed 544 by adding the additional comments and responses to the toxicology section of the 545 Response to Comments Document. 546 EPA carefully reviewed all comments submitted

. , and provides responses in the . 547 Response to Comments Document, a copy of which is available in the docket. The 548*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 23 of 233 Response to Comments Document is in the docket a t http://www.regulations.gov . As 549 previously discussed, the Re sponse to Comments Document also contains the rationale 550 for the changes that were made from the pro posed rule to the final rule, in response to 551 submitted comments. Simila r comments are grouped together. EPA selected the most 552 significant of the comments, such as those Comments that impacted the had a 553 substantive impact on changes from the proposed rule to the final rule , for inclusion are 554 also discussed in Units IV

. to XXII

. of this final rule document

. 555 D. B . Overview of this Final Rule 556 1. In general. This final rule reflects updates and revisions to the data 557 requirements currently contained in 40 CFR part 161, in many cases by codifying the 558 case-by-case data requirements decisions made over the years to help apply the 559 agriculturally-based 1984 data requirements to antimicrobial pesticide products. The 560 antimicrobial data r equirements are being added relocated to 40 CFR part 158, subpart 561 W

. , and 40 CFR part 161 is being removed. T his final rule will further enhance the 562 Agency's ability to make regulatory decisions about the human health, and 563 environmental fate and effects of antimicrobi al pesticide products. 564 Based on comments received, EPA revi sed the proposed data tables. EPA’s 565 Response to Comments Document is in the docket at http://www.regulations.gov . That 566 document contains the rationale for the changes t hat were made from the proposed rule 567 to the final rule , in response to submitted comments. 568 Eleven new data requirements for antimicrobial pesticides are being codified 569 today

. in this final rule. As discussed in the preamble to the proposed rule ( 73 FR 570 59387 ) , , a “new” data requirement “means that the data requirement has never been 571 required or has rarely been required on a case-by-case basis, and has not been 572 routinely considered during the Agency’s ev aluation of the data needed for the purpose 573*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 24 of 233 of risk assessment .” ” (73 FR 59387). Eight new data requirem ents that were proposed 574 in 2008 and are now being codified are: Deve lopmental neurotoxicity; immunotoxicity; 575 photodegradation in soil; soil residue dissi pation; ready biodegradability study; porous 576 pot study; activated sludge sorption isothe rm study; and modified activated sludge, 577 respiration inhibition test. The developmental neurotoxicity and immunotoxicity tests are 578 new compared to part 161, but were added for conventional pesticides in the 2007 579 amendments to part 158. The photodegradati on in soil study was not previously 580 required for wood preservatives. The other four studies ar e unique to antimicrobials. 581 Since the proposed rule , Based on comments received, t hree two other “ new ” 582 data requirements are also being added : that serve as alternatives to tests that were 583 proposed (and are now being finalized): Simulation tests to assess the biodegradability 584 of chemicals in discharged wastewater, and simulation test – aerobic sewage treatment: 585 activated sludge units , and . Similarly, also based on comments, one ”new” data 586 requirement, the nature of the residue on surfaces , is being added as a more definitive 587 trigger or screen for determining whether one of the studies that was proposed – the 588 migration study – must be conducted

. 589 Additionally, this final rule: 590

 Codifies data requirements/use pattern combinations that were not codified in 591 part 161, but have typically been required to r egister an antimicrobial pesticide product. 592

 Provides improved definitions for ant imicrobial pesticides used for public 593 health and nonpublic heal th purposes. 594

 Codifies data requirements to determi ne risks to waste water treatment plants 595 (WWTPs) and the potential for movement of antimicrobials and t heir degradates from 596 the indoor environment to the outdoor environment via effluent discharge from a 597 publically owned treatm ent work (POTW). 598*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 25 of 233 The data requirements promulgated today in this final rule identify the types of 599 information that EPA needs to determine whether a an antimicrobial pesticide product 600 should be registered , and to make decisions regarding tolerances or tolerance 601 exemptions for pesticide residues in food. Subpart W includes a series of tables and 602 regulatory text that mirrors the structure of the data requirements for conventional 603 pesticide s . However, subpart W establishes s pecific data requirements for each 604 scientific discipline (except product chemistry) for antimicrobial pesticides. As explained 605 in Unit IIIA., II.A. of this document, subpart D to part 158, which contains the product 606 chemistry data requirements for conventional pesticides, also applies to antimicrobials. 607 The order of subpart W also mi rrors that of the larger par t 158. As such, the following 608 data requirements categories ar e included in detail in part 158, subpart W: Product 609 performance, hazard/toxicity (both human heal th and ecological toxicity), exposure 610 (both application and post-application human exposures), residue chemistry, and 611 environmental fate requirements. 612 EPA is also codifying 12 antimicrobial us e patterns, as described in the proposed 613 rule (73 FR 59389

- 90 , October 8, 2008). As part of today’s action this final rule, EPA 614 has developed and will shortly post on the Agency’s website an Antimicrobial Use Site 615 Index to provide additional info rmation about these use patterns. This index is included 616 in the docket and is posted on the Agency’s website. 617 As promulgated, subpart W is intended to improve the scientific basis for 618 antimicrobial pesticide decisions. These efforts are expected to help protect human 619 heal th and the environment by providing an up

- to

- date scientific framework for 620 identifying and assessing the ri sks of antimicrobial pesticides sold or distributed in the 621 United States. 622*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 26 of 233 2. Changes to the from what was proposed rule

. In response to comments, EPA 623 has made numerous changes to the proposed rule requirements in crafting the final rule 624 promulgated today . The most significant changes are summarized below as follows

. 625 i. Alternatives to the porous pot study. With regard to the por ous pot study in the 626 final Environmental Fate Data Requirem ents Table in § 158.2280, EPA is adding two 627 simulation studies that can serve as an alter native to the porous pot study. This change 628 was based on a comment that reques ted consideration of whether “studies that simulate 629 wastewater treatment plants (WWTPs) [could] substitute for [the porous pot study].” 630 (ACC Comment identified in the docket at http://www.regulations.gov ; by document ID 631 number EPA-HQ-OPP-2008-0110-0088.9; Appendix H, entitled “Comments on 632 Proposed Data Requirements fo r Environmental Fate” p. 5). Additionally, in the 633 commenter’s suggested environmental fate dat a requirements table (p. 11), instead of 634 giving the title of the study as “Porous Pot,” the commenter wr ote “Simulated WWTP; 635 e.g., Porous Pot Study.” 636 EPA agreed with the comment er and identified two other studies: The 637 biodegradation in activated sl udge study as described in t he OPPTS guideline entitled 638 “Simulation Tests to Assess the Biodegr adability of Chemicals Discharged in 639 Wastewater” and simulation test – aerobic se wage treatment: activated sludge units. 640 This change provides applicants with more flex ibility in meeting this data requirement. 641 EPA’s rationale is described in Unit XV.A , ., and for greater detail see response to 642 comment 134.1 in the Response to Comments Document in the docket at 643 http://www.regulations.gov ). Testnote ). Test note 3 to the final Environmental Fate 644 Data Requirements Table in § 158.2280 clea rly specifies that only one biodegradation 645 study is to be submitted. 646*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 27 of 233 In creating a tiered struct ure for the Antimicrobial Environmental Fate Data 647 Requirements table, the table and accompanying test notes are intended to be used to 648 determine which antimicrobials would be expected to reach a WWTP. Test notes 18, 649 19, 20, and 21 to the Environmental Fate Data Requirements table discuss specific 650 criteria for determining whether data from a biodegradation study, the activated sludge 651 sorption isotherm study, and the activated sludge respiration inhibition test are required 652 for a particular product based on its intended uses. 653 ii. Trigger for migration study. EPA made changes to the trigger for the 654 migration study in the final Residue Chemistry Data Require ments in § 158.2290. In its 655 proposed rule, EPA “triggered” the migration study based on anticipated instances such 656 as theoretical (modeled) estimates yieldi ng a risk of concern. One commenter 657 submitted a suggested residue chemistry da ta requirements tabl e with a line-item 658 entitled “Nature of residue of surface.” (ACC Comment , identified in the docket at 659 http://www.regulations.gov ; by document ID number EPA-HQ-OPP-2008-0110-0088.10; 660 Appendix I, entitled “Comments on Propos ed Data Requirements for Residue 661 Chemistry” p. 7). A differ ent commenter also submitted a different residue chemistry 662 data requirements table, which also included the same li ne-item entitled “Nature of 663 residue on surface.” (CSPA Comment , identified in the docket at 664 http://www.regulations.gov ; by document ID number EPA-HQ-OPP-2008-0110-0086.2). 665 The commenters’ suggestion of requiring a nature of the residue study on 666 surfaces provides a more definitive trigger for the migration study. EPA is adding a 667 nature of the residue on surfac es study. As specified in testnote 3 test note 5 to the final 668 Residue Chemistry Data Requirements Table, t he results of the nature of the residue on 669 surfaces study will serve as a trigger for determining whether the migration study will 670 need to be performed. EPA consi ders the commenters’ suggestion s to be a valuable 671*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 28 of 233 addition to the final Residue Chemistry Data Requirements Table in § 158.2290 that 672 provides more definitive triggers to help def ine and narrow the instances of higher-tiered 673 testing. 674 iii. Changes to data requirement s for wood preservatives. As discussed in Unit 675 VI.B , ., EPA’s current practice of determining t he data required for a wood preservative 676 product is dependent upon where the product is intended to be used (land-only versus 677 land and aquatic). This approach also assume s that diversion does not occur and that 678 wood that is treated for land-only uses does not end up in the water and vice versa. In 679 practice, it is difficult to a ssure that diversion does not occu r. Accordingly, in response 680 to comments, the Agency det ermined that all treated wood needs to be considered as 681 having the potential to come into contact with surface water. Ther efore, for the final 682 Environmental Fate Table, for the wood pres ervatives column, the data requirements for 683 anaerobic soil metabolism, aer obic aquatic metabolism, and anaerobic aquatic 684 metabolism were changed from “CR” to “R.” For the final Nontarget Organism Table, 685 for the wood preservatives column, the data requirements for chronic toxicity testing 686 with fish (fish early-life stage) and aquatic in vertebrate (aquatic invertebrate life-cycle) 687 are being changed from “CR” to “R” to provi de chronic data when chronic exposure is 688 expected. With regards to the three acute toxicity test s conducted with the TEP, the 689 “NR” in the wood preservatives column is changed to “CR.” Additionally, EPA will 690 perform a down

- the

- drain analysis for every product with an applicable use or 691 exposure scenario, including wood preservati ves, that has the potential for waters 692 containing antimicrobials to reach a WWTP. Therefore, to perform this analysis, the 693 Agency is requiring data on the biodegradati on of a wood preservative and its potential 694 toxicity to WWTP microorganisms in an activated sludge basin. 695*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 29 of 233 iv. Changes to data require ments for antifoulants. Antifoulants are 696 released/applied directly to the aquatic environment. These products are often 697 manufactured to be persistent, and because of the continuous release process, some of 698 the active ingredient is likely to be transfe rred to the bottom of the water column, and 699 then be adsorbed to the sediment. Ther efore, EPA is changing, in the final 700 Environmental Fate Data Requirements Table, the “CR” for the a quatic sediment study 701 for the antifoulant paint and coatings column to “R.” With regards to the three acute 702 toxicity tests conducted with the TEP, the “NR” in the antifoulant paint and coatings 703 column is changed to “CR.” Also, to perform a down

- the

- drain analysis, the Agency is 704 requiring data on the biodegrada tion of an antifoulant and its potential toxicity to WWTP 705 microorganisms in an activated sludge basin. 706

v. Non-dietary ingestion. EPA proposed to require this post-application 707 exposure study. However, EPA agrees that in stead of requiring this study, it is more 708 likely that EPA would model this route and pathway of exposure using inputs from 709 available and reliable published research. Therefore, EPA has removed this data 710 requirement from the final Post -Application Exposure Table. 711 vi. Re-structuring of proposed toxicology and residue chemistry data 712 requirement tables. In the proposed rule, for the toxi cology data requirements table, 713 EPA separated those use patterns needing more toxicology data from those needing 714 less toxicology data using a terminology des cribed as high or low. Based on comments 715 received, in this final rule, EPA is now using a food/nonfood approach with some 716 similarities to that of the toxicology data requirements tabl e for conventional pesticides 717 to distinguish the use pattern s that need more toxicity data from those that need less. 718 The food-use column and the nonfood-use column are split into subcolumns to explain 719 which food-uses or nonfood-uses require more data, and which require less. This 720*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 30 of 233 modification of the food/nonfood approach de lineates the specific data requirement 721 needs for antimicrobial pesticides. 722 For the final Residue Chemistry Data Requirements Table, EPA has adopted the 723 commenters’ suggestion for a tiered format. After review of the commenter’s suggested 724 tables, EPA believes the commenters’ sugges ted tiered approach is more suitable to 725 antimicrobials than that proposed by EPA. 726 vii. Change in terminology. The commenters’ asserted that the use of terms 727 such as” high” or “low” as a mean s of tiering was insupportable, and an 728 “unsubstantiated assignment of exposure categories” (ACC Comment , identified in the 729 docket at http://www.regulations.gov ; by document ID number EPA-HQ-OPP-2008- 730 0110-0088.1 , p. 21 and 22). EPA continues to belie ve that the use of “high” and “low” 731 categories of exposure defined by the antimicr obial use patterns are a valid method for 732 identifying those exposures that have gr eater exposure and thos e that have less. 733 Based on its experience, EPA understands wh ich use patterns require more data. 734 However, EPA can achieve the same result without the use of the terms “high” or “low.” 735 Therefore, based on comments received, EPA notes that it is no longer using the terms 736 “high human exposure” and “low human expo sure” as table headers for the final 737 Antimicrobial Toxicology Data Requirements Table. Similarl y, EPA is no longer using 738 the terms “high environmental exposure” and “low environmental exposure” as table 739 headers for the final Antimicrobial Nontarget Organism, the Nontarget Plant Protection, 740 or the Environmental Fate Data Requirement s Table. However, EPA also notes that 741 terms such as “high human exposure , ,” “low human exposure , ,” “high environmental 742 exposure” and “low environmental exposure” can be appropriate when discussing a 743 particular antimicrobial use. A statement that a particular use results in, for example, 744*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 31 of 233 “high environmental exposure” provides info rmation and alerts t he reader that more 745 data are likely to be needed, ra ther than less data. 746 IV. Scope of the Rule 747 This rule establishes a separate listi ng in Title 40 of the Code of Federal 748 Regulations (CFR) for EPA’s data require ments under FIFRA and FFDCA section 408 749 for antimicrobial pesticide uses. Althoug h the rule is tailored to the unique 750 characteristics of antimicrobial pesticides , it builds upon the ex isting data requirements 751 imposed in 1984 on all pesticides and the 2007 amendments to th ose requirements 752 pertaining to conventional pesticides. Both sets of data requirements – conventional 753 and antimicrobial – are designed to provide EPA with the information needed to make 754 the required regulatory determinations und er FIFRA and FFDCA section 408. FIFRA 755 provides that a pesticide may not be register ed for sale, distribution, and use unless “it 756 will perform its intended function without unreasonable adverse effects on the 757 environment . . . .” [7 U. S.C. 136a(c)(5)(C)]. FIFRA defines “unreasonable adverse 758 effects on the environment” as both “any unreasonable risk to man or the environment” 759 and “a human dietary risk . . . inconsistent with the standard under section 408 of the 760 [FFDCA]” [7 U.S.C. 136(bb)]. FFDCA section 408 directs that EPA shall not establish a 761 tolerance permitting pesticide residues in food unless EPA determines that the 762 tolerance is “safe” [21 U.S. C. 346a(b)(2)(A)(i)]. “Safe, ” under FFDCA section 408, is 763 defined as “a reasonable certainty that no harm will result from aggregate exposure to 764 the pesticide chemical residue, including a ll anticipated dietary exposures and all other 765 exposures for which there is reliable info rmation” [21 U.S.C. 346a(b)(2)(A)(ii)]. In 766 making safety determinations, EPA is requi red to consider aggregate and cumulative 767 exposures from pesticides and other related s ubstances and multiple factors specifically 768 related to the protection of childr en [21 U.S.C. 346a(b)(2)(C) and (D)]. 769*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 32 of 233 Under FIFRA, EPA has required “[s]ubstant ial amounts of data on the pesticide, 770 its composition, toxicity, potential hum an exposure, environmental properties, and 771 ecological effects, as well as information on its product per formance (efficacy) in certain 772 cases” (73 FR 59384, October 8, 2008). Since 1984, EPA has had codified FIFRA data 773 requirements mandating data on, among other things, the toxicity hazards from 774 ingestion of pesticides and exposure leve ls of pesticide residues in food (Ref. 1 2 ). With 775 the passage in 1996 of the Food Quality Protection Act, [Public Law 104-170, 110 Stat. 776 1489 (1996)], which added the expanded safe ty standard in FFDCA section 408 777 described above previously , EPA’s data needs have expanded. As noted in the 778 preamble to the proposed rule, “[t]he co mbination of aggregate and cumulative 779 exposure assessments required by FFDCA se ction 408 increases the nature and scope 780 of EPA’s risk assessment, and potentially in creases the types and amounts of data 781 needed to determine that the FFDCA safety st andard is met” (73 FR 59385, October 8, 782 2008). Moreover, with the explicit linka ge in FIFRA between the FIFRA and FFDCA 783 section 408 safety standards (also added by FQPA), “[t]he data required to support a 784 determination of ‘reasonable certainty of no harm’ under FFDCA are an integral part of 785 the data needed for an ‘unreasonable adverse effe cts’ determination under FIFRA” [Id.; 786

see 72 FR 60934 ( , October 26, 2007 ) ( (FRL 8106-5), recodifying part 158 data 787 requirements under the authority of both FIFRA and FFDCA section 408 )]. ]. This rule 788 establishing specific data requirements fo r antimicrobial pesticides is designed to 789 capture the broad range of data needed to asse ss the safety of pesticides under the 790 standards of both FIFRA and FFDCA section 408. 791 The ACC Biocides Panel and other comment ers, however, have claimed that the 792 scope of the proposed rule exceeds the EPA ’s statutory author ity because EPA is 793 asserting “jurisdiction under FI FRA over some antimicrobial food uses where, in the 794*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 33 of 233 Panel’s view, the statutory scheme provides exclusive jurisdiction to FDA” (Food and 795 Drug Administration ) ). (ACC Comment identified in the docket at 796 http://www.regulations.gov ; by document ID number EPA-HQ-OPP-2008-0110-0088.1 , 797 p. 31). Although the ACC Biocides Panel ac knowledges that these uses are properly 798 regulated by EPA as “pesticides” under FI FRA, the Panel argues that “EPA’s 799 responsibility for such use[s] is to evaluate whether the antimicrobial m eets the standard 800 for registration under FIFRA, taking into a ccount FDA’s existing regulatory finding 801 [under FFDCA section 409]. . . . EPA does not have the authority under either FIFRA 802 or FFDCA to review or change the terms of the FDA approval.” (ACC Comment , 803 identified in the docket at http://www.regulations.gov ; by document ID number EPA-HQ804 OPP-2008-0110-0088.1 , p.33). In essence, the Pane l is asserting that for these 805 antimicrobial uses, EPA is wit hout authority or jurisdiction under FIFRA to evaluate, or 806 require data on, the level of risk from dietar y exposure to the antimicrobial – where FDA 807 has evaluated the safety of the use of the substance under section 409. As a basis for 808 this argument, the ACC Biocides Panel points to the Antimicrobial Regulation Technical 809 Corrections Act (ARTCA), [Public Law 105-324, in 1998], which divided FFDCA 810 jurisdiction between EPA and FDA with respect to antimicrobials. The Panel further 811 argues that EPA is wrong to rely on FIFRA section 2(bb)’s inclusion of the FFDCA 812 section 408 safety standard in the definit ion of “unreasonable adverse effects” as 813 authority for requiring data on antimicrobial uses falling under FDA’s FFDCA section 814 409 jurisdiction. Labeling EPA’s interpretati on of FIFRA section 2(bb) in the proposed 815 rule as “new,” the ACC Biocides Panel claims that EPA has contradicted its “long816 standing” interpretation of this provision. 817 The ACC Biocides Panel fundamenta lly misunderstands EPA’s statutory 818 authority under FIFRA to require data pertaini ng to dietary risk from pesticides. EPA’s 819*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 34 of 233 authority to regulate pesticides under FIFRA with regard to t heir dietary risk is derived 820 from FIFRA not the FFDCA. Under FIFRA, EPA is charged with protecting the public 821 from “unreasonable adverse effe cts on the environment.” As noted above previously , 822 FIFRA in section 2(bb) defines “unreasonable adverse effects” in the first instance as 823 “any unreasonable risk to man . . . .” [7 U.S.C. 346(bb)]. This broad standard clearly 824 encompasses any unreasonable dietary risk. EPA’s authority to regulate pesticides 825 under FIFRA on the basis of dietary risk is exp licitly reinforced by the second part of the 826 unreasonable adverse effects standard which directs EPA to evaluate “human dietary 827 risks” from “pesticides” under the safety st andard in FFDCA sect ion 408. [Id.] 828 Nothing in FIFRA or the FFDCA limits or c onstrains EPA’s authority or jurisdiction 829 to regulate pesticides based on dietary risk under FIFRA section 2(bb). The FIFRA 830 section 2(bb) standard is i ndependent from the safety st andard under FFDCA section 831 409. Further, any finding by EPA under FI FRA that considers dietary risk would not 832 “change the terms of a FDA approval;” rather, it would simply be a determination as to 833 whether the separate FIFRA regulatory standard had been met. Finally, contrary to the 834 ACC Biocides Panel’s contention, the adj ustment by the ARTCA of EPA’s and FDA’s 835 jurisdiction under FFDCA sections 408 and 409 over antimicrobial s does not affect 836 EPA’s jurisdiction or authority with regard to dietary risks of pesticides under FIFRA. In 837 fact, as explained below further in this unit , not only did the ARTCA not amend FIFRA 838 section 2(bb) but Congress in the ARTC A took the unusual step of expressly 839 disavowing any intent to narrow the scope of EPA’s authority under FIFRA. 840 The ARTCA was follow-on legislati on to the major 1996 FFDCA amendments 841 which, among other things, changed EPA and FD A jurisdiction under FFDCA sections 842 408 and 409. Prior to 1996, se ction 408 of the FFDCA, which is administered by EPA, 843 only applied to “pesticide chemicals” that we re defined as FIFRA “pesticides” “used in 844*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 35 of 233 the production, storage, and tran sportation of raw agricultural commodities” [21 U.S.C. 845 321(q) (1994)]. FIFRA pesticide residues in food not falling within this provision (i.e. 846 FIFRA pesticides used later in the food pr oduction process than the growth of raw 847 agricultural commodities) came under sect ion 409 of the FFDCA as food additives [ See 848 21 U.S.C. 321(s), 348 (1994)]. FDA administers the est ablishment of food additive 849 regulations under FFDCA section 409. M any antimicrobial pesticides used in 850 conjunction with the manufacturing and processi ng of foods, at that time, were regulated 851 as food additives. This division of legi slative authority was c hanged by the FQPA in 852 1996. The FQPA amended the definit ion of “pesticide chemical” in the FFDCA to make 853 it co-terminous with the definit ion of a “pesticide” in FI FRA by deleting the language 854 restricting pesticide chemicals to those pesticides used in the production of raw 855 agricultural commodities. Correspondingl y, the FQPA also excluded “pesticide 856 chemicals” from the def inition of a “food additive” [Public Law 104-170 § sec. 402, 110 857 Stat. 1489, 1513 (1996)]. This change had the effect for FFDCA purposes of bringing 858 all FIFRA pesticides under FFDCA secti on 408. Not only did Congress consolidate 859 regulation of all pesticide residues in FFDCA section 408 but it also amended FIFRA to 860 insure that the new safety standard in FFDCA section 408 was part and parcel of the 861 FIFRA registration standard for pesticides re sulting in residues in food [7 U.S.C. 862 136(bb)(2)]. Specifically , as noted above , in section 2(bb)(2), Congress defined an 863 “unreasonable adverse effect on the envir onment” under FIFRA as “a human dietary 864 risk from residues that result from a use of a pesticide in or on any food inconsistent 865 with the standard under FFDCA section 408 of the Federal, Food, Drug, and Cosmetic 866 Act [21 U.S.C. 346a].” 867 In 1998 in the ARTCA, Congress modifi ed slightly its FFDCA decision to 868 consolidate all pesticide chemical residues in foods under FFDCA section 408. ARTCA 869*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 36 of 233 amended the definition of “pesti cide chemical” in FFDCA sect ion 201 to exclude certain 870 antimicrobial substances from the coverage of the definition [ See 21 U.S.C. 321(q)]. 871 More specifically, with certain qualifications, the ARTCA excepted, from the definition of 872 pesticide chemical, substances that are FIFRA pesticides and are “applied for [an 873 antimicrobial] use on food, or the substance is included for such use in water that 874 comes into contact with food, in the prepar ing, packing, or hol ding of the food for 875 commercial purposes.” [21 U.S.C. 321(q)(1 )(B)(i)]. In addi tion, ARTCA excepted 876 substances from the definition of pesticide chemical that are food contact substances, 877 as defined in section 409(h)(6) of the FFDCA , based on certain circumstances related to 878 their use. These antimicrobi al substances were now no longer considered “pesticide 879 chemicals” under the FFDCA but fell under t he definition of “food additive.” That had 880 the effect of shifting the re sidues resulting from these antimicrobial substances from 881 FFDCA section 408 to FFDCA section 409 and shifting agency jurisdiction under the 882 FFDCA over the same from EPA to FDA. Importantly, Congress, in ARTCA, did not 883 amend FIFRA to remove these uses of antimic robial substances fr om the definition of 884 “pesticide” under FIFRA and left unchanged FI FRA section 2(bb)(2) which mandates 885 that the section 408 safety standard is par t of FIFRA’s unreasona ble adverse effects 886 standard as to FIFRA “pesticide” residues on food. Thus, EPA retained FIFRA 887 jurisdiction over these antimicrobial s ubstances (because they remained FIFRA 888 “pesticides”) while FDA re-acquired FFDCA jurisdiction over them under FFDCA section 889 409 (because they were remov ed from the definiti on of “pesticide chemical”). To make 890 clear its intent on EPA’s FIFRA jurisdicti on, the ARTCA included the following express 891 disavowal which was inserted into the FFDCA definition of “pesti cide chemical:” 892 With respect to the definition of the term ‘pesticide’ that is applicable 893 to the Federal Insecticide, Fungi cide, and Rodenticide Act, this clause 894 [excluding certain antimicrobial s ubstances from the FFDCA definition 895*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 37 of 233 of “pesticide chemical”] does not exclude any substance from such 896 definition” [21 U. S.C. 321(q)(1)(B)]. 897 898 Since its passage, EPA has interpret ed the ARTCA according to its plain 899 language, excluding the desig nated antimicrobial substances from the coverage of 900 FFDCA section 408 but continuing to regulat e those antimicrobial substances that 901 qualify as FIFRA “pesticides” under FIFRA and requiring that , when those antimicrobial 902 pesticides result in residues in food, the ri sks from such residues be consistent with the 903 safety standard in FFDCA sect ion 408. After all, FIFRA se ction 2(bb)(2), on its face, 904 applies to FIFRA “pesticides” and not FFDCA “ pesticide chemicals.” Any other result 905 would be directly contrary to Congress’ dictat e that it was not excluding any substances 906 from the FIFRA def inition of “pesticide.” Accordi ngly, it is well within EPA’s FIFRA 907 authority to require that data be submitted on pesticides to determine if those pesticides 908 meet the FFDCA section 408 safety standard, whether or not t hose pesticides come 909 within the definition of a FFDCA “pesticide chemical,” so long as the use of those 910 pesticides results in residues in food. On the other hand, the ACC Biocides Panel’s 911 approach would involve amendi ng the language of section 2(bb)(2) in a manner 912 specifically rejected by the Congress when it passed ARTCA. 913 There is no basis for the ACC Biocide Panel’s claim that EPA’s interpretation of 914 FIFRA section 2(bb)(2) is “new.” The best evidence of the consistent and long-held 915 nature of EPA’s interpretation are the numer ous submissions to the Agency from the 916 Panel (and others) over the la st 10 years disputing EPA’s plain language approach to 917 FIFRA section 2(bb)(2). (Refs. 2 , 3, 4, 5, 6, 7, 8, 9, 10 and 10 11 ) 918 V. Discussion of Several V. Issues Repeated Throughout Most Comments 919*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 38 of 233 In evaluating the comments receiv ed on proposed part 158, subpart W, EPA 920 noted that four specific comm ents were routinely repeated th roughout most of the entire 921 set of comments. 922 A. Differentiating the Review of Antimicrobials 923 1. Comment. EPA received several comment s noting that FIFRA section 924 3(h)(3)(A)(ii) specifies that EPA must differentia te the review of antimicrobial pesticides 925 from that of other pesticides. 926 2. EPA’s response . FIFRA section 3(h)(3)(A)(ii) specifies, among other things, 927 that, in proposed regulations to accelerate and improve the review of antimicrobial 928 pesticide products, EPA shall define the various classes of antimicrobial use patterns, 929 differentiate the types of review undertak en for antimicrobial pesticides, conform the 930 degree and type of review to the risks and benefits presented by antimicrobial 931 pesticides, and ensure that the re gistration process is sufficient to maintain antimicrobial 932 product efficacy. While those elements apply to a proposed rulemaking that the Agency 933 published on September 17, 1999 (64 FR 50671 ) (FRL 5770-6 ), the Agency has been 934 mindful of those same elements in its devel opment of part 158, subpart W. As applied 935 to antimicrobial product registration actions, di fferentiation refers to the tailoring of data 936 requirements so that they are responsive to considerations about the antimicrobial 937 products to which they relate. In prac tice, differentiation means that the data 938 requirements applied to antimicrobials are de signed to respond to the special or unique 939 needs of antimicrobials such as the nature of the products, their i ngredients, their uses, 940 etc. Differentiation or tailo ring does not mean that the resulting data requirements for 941 antimicrobials will necessarily be comprised of more, less, or the same number and type 942 of data requirements as required for other types of pesticides such as conventional 943 pesticides. 944*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 39 of 233 For example, the residue chemistr y data requirements for conventional 945 pesticides focus on the application of agricul tural pesticides to crops growing in the 946 fields. However, the residue chemistry dat a requirements for antimicrobials, codified 947 today in this final rule , have been tiered to account for a pplications that focus not on 948 crops growing in the fields (where antimicr obials are rarely used), but instead account 949 for antimicrobial uses, including those that result in residues on food more indirectly, 950 such as from use as sanitizers in food processing plants. The overall impact is to 951 require fewer studies since the tiering used fo r the antimicrobial residue chemistry data 952 requirements table is structured differently , and there are fewer “R” studies and most 953 studies are “CR.” However, there ar e two residue chemistry data requirements 954 (migration and nature of the residue on surfaces ) for antimicrobials that are not included 955 in the conventional residue chemistry data r equirements table because they reflect the 956 unique use sites for antim icrobials; see Unit XVI

. for additional discussion. Ecotoxicity 957 and environmental fate data requirements prov ide another example of the differentiation 958 of data requirements between antimicrobial s and conventional pesticides. While 959 conventional or biochemical/microbial pes ticides are often used outdoors, and are 960 deliberately placed/spread in the environment, most antimicrobials are used indoors. 961 As discussed in the preamble (73 FR 59406) , previously EPA had assumed that many 962 of the indoor uses went down

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- drain to a waste water treatment plant ( WWTP ), , 963 where the WWTP processes would mitigate env ironmental concerns. Therefore, in 964 1984, EPA required basic ecotoxicity and env ironmental fate data for conventional 965 pesticides but made these types of data conditional for indoor uses such as 966 antimicrobials based on whether antimicrobial-specific data indicated that environmental 967 exposure may occur. Howeve r, as discussed in the proposed rule (73 FR 59407), in 968 recent years there have been detections of antim icrobial chemicals (with indoor uses) in 969*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 40 of 233 waterbodies. These antimicrobials are movi ng into the environment via treated effluent. 970 Therefore, EPA is requiring for antimicrobials a specific tier ed-set of data to evaluate the 971 likelihood of environmental ex posure to antimicrobials that may reach a WWTP, as a 972 result of being washed down the drain via leachates, rinsates, and flushes. These data 973 evaluate whether antimicrobials are likely to survive the trea tment processes at a typical 974 WWTP, and thus would be present in the WW TP effluent. Antimi crobials that do 975 survive the treatment processes have the potent ial to end-up in the terrestrial or aquatic 976 environments and higher-tiered ecotoxicity and environmental fate data are only 977 triggered for these antimicrobials. 978 Thus, differences in data requirements stem directly from the inherent differences 979 in the nature of the particular type of pesticide's use. pesticide used. Even with such 980 differentiation or tailoring, there is a gener al core of data requirements which may be 981 expected to be applicable to any kind of pes ticide product, such as product chemistry 982 data requirements. EPA’s ultimate goal with its antimicrobial data requirements is to 983 create a body of data requirements wh ich produce sufficient information for the Agency 984 to consider and use in making its statutor ily-required determinations regarding the risks 985 and benefits, where applicable, of antimicrobi al pesticides. The differentiation or 986 tailoring of the antimicrobial data requirements is instrum ental in accomplishing that 987 goal. 988 B. Rewrite and Repropose the Rule 989 Several commenters requested that EPA re write and then repropose this rule. 990 Commenters raised three arguments as to why EPA should repropose. First, the 991 proposed regulation does not c ontain scientifically-based crit eria for determining data 992 requirements but instead requires that dat a requirements be determined in case-by993 case consultations in which EPA retains “s ole discretion” as to the data required. 994*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 41 of 233 Second, EPA has not disclosed how it plan s to use the proposed data in EPA risk 995 assessments. Third, affect ed parties cannot properly ev aluate the data requirements 996 without final guidelines on how su ch studies should be conducted. Each of these three 997 arguments are addre ssed in detail below in the following responses

. 998 1. Comment on scientific ally-based criteria . Several commenters focused on the 999 testnotes test notes to the data requirements tables, and claimed that the proposed rule 1000 “leaves too many standards and decisions to the sole discretion of EPA, creating 1001 uncertainty and, inevitability, inconsistency in regulatory decision making.” Too many 1002 determinations, the commenter asserted, are at “EPA’s discretion” because the 1003 proposal is vague , without clear-cut criteria . Additionally, they ar gued that there are too 1004 many places in the test notes where cons ultation with the Agency is required or the 1005 phrase “as determined by the Agency” is us ed. (One commenter listed 37 instances in 1006 which the proposal allegedly substitut ed a mandatory consultation process for 1007 regulatory criteria.) Accord ing to the commenters, EPA should eliminate most of the 1008 consultation requirements and instead, repr opose the rule providing a clear set of 1009 requirements. 1010 2. EPA’s response to comment on scientifically-based criteria . Test notes often 1011 contain qualitative or quantitative measures for use in determining whether a study is 1012 triggered or not. Most frequently this occurs w hen there is an initial study that relates to 1013 whether subsequent testing would be needed or not. Not all triggers are easily 1014 reduceable to quantitative meas ures and EPA believes that qualitative descriptors such 1015 as “expected to enter the environm ent in significant concentrations,” or “if repeated 1016 dermal exposure is likely to occur under condi tions of use,” and “the use of the pesticide 1017 is likely to result in repeated human exposure over a limited considerable portion of the 1018 human lifespan” provide meaningful criteria for determining when a study is triggered. 1019*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 42 of 233 EPA has carefully reviewed each of the 37 te st notes cited by one commenter and has 1020 identified several instances in which clarific ation of the criteria was appropriate. EPA’s 1021 analysis of these 37 test notes and result ant changes are included in response to 1022 comment 3 in the Response to Comments Document in the docket at 1023 http://www.regulations.gov

. . 1024 In numerous places the test notes cont ain language stating that the criteria would 1025 be applied “as determined by the Agency.” Co mmenters have misinterpreted this as 1026 giving EPA the authority to make decisions on factors other than th e regulatory criteria 1027 included or in its “sole discretion.” This was not EPA’s intent and, accordingly, EPA has 1028 removed all of the phrases “as determined by the Agency” fr om all test notes for the 1029 final antimicrobials rule so there can be no chance of a misunderstanding of how the 1030 criteria are to be applied. 1031 Commenters also asserted that the EPA’s alleged mandatory consultation 1032 requirements rendered the test notes meani ngless, as EPA would determine whether 1033 studies were required in private based on un specified factors. EPA disagrees. The 1034 commenters have misread the proposed rule language and misund erstood the purpose 1035 for consultation. The consultation refer ences were not intended to impose a mandatory 1036 consultation requirement. To the contrary, the references to consultation was were an 1037 attempt by EPA to signal its willingness to meet with applicants to adapt studies, if 1038 necessary, to the specifics of individual antimicrobials. 1039 Consultation is a longstanding, commonly used and valuable process in EPA’s 1040 Pesticide Program. Applicant s often meet with OPP staff on a pre-submission basis to 1041 review and discuss the adequacy of the avail able data. OPP believes that such 1042 meetings are beneficial to both EPA and the applic ants. In practice, such meetings are 1043 very often sought by registrants and appl icants. By encouraging communication and 1044*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 43 of 233 exchange of ideas, such discussions can help in the development of clearer 1045 expectations of what must be submitted in instances where data requirements involve 1046 complexities. Consultation can result in data that better meets EPA’s needs and saves 1047 resources for both EPA and the applicant. Depending upon what is intended to be 1048 addressed, such meetings do not necessarily need to be held in person, but can be 1049 frequently accomplished via tele-conferencing. 1050 EPA did not intend its references to cons ultations in the test notes to impose 1051 mandatory consultation requirements; nei ther did EPA intend the consultation 1052 references as a means of establishing a di fferent standard for determining if a study is 1053 triggered. EPA has carefully reviewed all test notes in the antimicrobials final rule and 1054 removed all references to consultation from all testnote s test notes for the antimicrobials 1055 rule so there can be no chance of mi sunderstanding the vol untary nature of 1056 consultation. 1057 3. Comment on use of data in risk assessment. The commenters also argued 1058 that reproposal was necessary because t hey could not meaningfully comment on the 1059 proposal without understanding how the data woul d be used by EPA. Specifically, one 1060 commenter wrote: “It is not plausible fo r [the commenter] or ot hers to meaningfully 1061 comment on the Proposal without the benef it of understanding the risk assessment 1062 approaches EPA plans to use, (e.g., human and ecological), the ways in which the data 1063 requirements will provide information to conduct those assessments and the ways EPA 1064 will use those risk assessments in making regulatory decisions. 1065 4. EPA’s response on use of data in risk assessment. EPA disagrees with this 1066 comment for several reasons. First, how EPA conducts risk assessments and how it 1067 uses toxicological, ecological, and expos ure data in those risk assessments is well 1068 known. Risk assessment is not unique to O PP. The principles used by OPP and, in 1069*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 44 of 233 fact, by EPA are those used by the scientific community in general. OPP follows the 1070 processes and procedures in the many risk assessment guidance do cuments that have 1071 been issued by EPA (see http://www.epa.go v/riskassessment/guidance.htm). The 1072 Agency’s exposure and risk assessment pr ocedures have been presented in numerous 1073 exposure and risk assessments for antimicr obial pesticides. EPA’s assessments reflect 1074 the best available data, and the st ate of the science of ex posure and risk assessment 1075 models, methods, and procedures. 1076 Moreover, OPP’s risk assessment pr ocedures for pesticides are well1077 documented. EPA has recently concluded the process of completing Reregistration 1078 Eligibility Decision Documents for all pesticides under FIFRA and reassessing all 1079 FFDCA pesticide tolerances. This was a very open process involving multiple public 1080 comment opportunities as to each pesticide. Further, all regulatory decision documents 1081 as well as the underlying risk assessments have been made available to the public. 1082 EPA has now begun new pesticide reviews under t he Registration Review program, and 1083 that process is equally open and transparent. 1084 A second reason why EPA believes this comm ent to be misdirected is that the 1085 proposed rule does not represent a c hange to EPA’s existing and transparent risk 1086 assessment procedures. Rather, the proposal is merely designed to tailor the existing 1087 data requirements that apply to all pesticides in a way that is more specific to 1088 antimicrobial pesticides, as well as includ ing some new requirements applicable to 1089 antimicrobials. 1090 Finally, the comment is without foundat ion because EPA has explained the need 1091 for each study and provided background information on the purpose for which each 1092 study would be required. Part 158, subpart B contains an extensive description of the 1093 need for and use of submitted studies (40 CFR 158.130). Additionally, as explained in 1094*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 45 of 233 the preamble to the antimicr obials proposed rule, EPA relied on the proposed and final 1095 rules for establishing data requirements for conventional pesticides. As stated in the 1096 proposed rule for antimicrobials, the rational es for requiring and/or revising particular 1097 data requirements were in those rules. 1098 With few exceptions, these rationales are also applicable to 1099 antimicrobial pesticide chemicals, and as such have not been 1100 repeated in today’s proposed rule. Today’s proposal discusses in 1101 detail only those revisions that are singularly applicable to 1102 antimicrobial pesticides, in cluding antifoulants and wood 1103 preservatives.” (73 FR 59384 ) ). 1104 1105 Examples of studies applicable to ant imicrobial pesticides and for which a 1106 description of the need for t he requirement was included in the preamble to the 1107 proposed rule for antimicrobials include the need for: 1108

 The 90-day dermal and 90-day inhalation studies for a heating, ventilation, air 1109 conditioning, and refrigerat ion uses ( 73 FR 59395), 1110

 A food migration study (73 FR 59404), and 1111

 Environmental fate studies to support a down

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- drain assessment (73 FR 1112 59408). 1113 One commenter presented several exampl es of what the commenter labeled as 1114 EPA’s “ad hoc risk assessment processes.” An examination of t hose examples shows 1115 that the commenter is concer ned with what it labels as “inconsistency in EPA’s current 1116 practice” as to when a dietary risk asse ssment is needed for antimicrobial pesticides. 1117 The commenter argued that this alleged inconsistent practice shows the “need for 1118 stable, transparent guidance on risk asse ssment to support data requirements 1119 regulation.” EPA does not believe that it has been inconsistent in its risk assessments. 1120 Furthermore, EPA does not believe that such “inconsistencies,” if they exist, would 1121 mean that affected parties could not co mment meaningfully on the proposed data 1122*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 46 of 233 requirements. Ultimately, t he issue with the data requirements rule is whether EPA has 1123 asked for data needed for determining whether pesticides meet the relevant statutory 1124 safety standards. The fact that EPA might have been inconsistent in the past in its 1125 determinations with regard to the safety standard or how it went about assessing 1126 whether a pesticide met the safety standards (e.g., did EPA need to do a dietary risk 1127 assessment), does not handicap an affected par ty in determining whether a proposed 1128 data requirement is consistent with the statutory safety st andards. To reiterate, the 1129 relevant question is not whether EPA has guidance on when dietary risk assessment is 1130 needed but whether the proposed data requirem ents pertaining to dietary risk would 1131 require information that are appropriate to EPA’s determination under the applicable 1132 statutory safety standards. To the ex tent, the commenter is concerned with any 1133 particular Agency decision regarding when a dietary risk assessment is needed for 1134 antimicrobials, EPA encourages the commenter to raise that concern directly with the 1135 Agency in the context of the specific ma tter causing the comment er concern. 1136 This commenter later filed additio nal comments that further developed the 1137 argument that reproposal is necessary bec ause EPA allegedly has not clearly defined 1138 when a dietary risk assessment is needed. The commenter wrote: “[T]he Proposal 1139 does not clearly articulate any standar ds for determining what uses trigger s a food 1140 analysis. It has become apparent since the Pr oposal was issued t hat the Agency will 1141 interpret this regulation to vastly increase the number of antimicr obials regulated as 1142 food use.” (ACC/CSPA letter , identified in the docket at ; by document ID number EPA1143 HQ-OPP

. - 2008-0110-0107, p. 2) . Further, the commenter then asserts that “EPA’s 1144 economic analysis does not even attempt to address the increase in the burden on 1145 registrants and applicants that this [alleged] expansion of the need for ‘food contact’ 1146 approvals will cause.” (Id.) These additional comments suggest that this commenter is 1147*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 47 of 233 concerned with EPA decisions issued prior to today’s this final rule (and, in most cases, 1148 prior to issuance of the proposed rule) and fear s how the final rule may be interpreted in 1149 the future. However, it is difficult to determine from these comments whether the 1150 commenter is claiming that this alleged “expansion” of food use antimicrobials is 1151 effected by any particular language in the pr oposed rule. To the ex tent the commenter 1152 is arguing that the expansion is caused by EPA’s application of t he FFDCA section 408 1153 standard to all antimicrobial food uses under FIFRA section 2(bb) (whether the use 1154 requires clearance under FFDCA section 408 or 409), the co mmenter, as explained in 1155 Unit XVI.A , ., misunderstands EPA’s aut hority under FIFRA and EPA’s practice as to 1156 antimicrobials since the passage of ARTCA. In another place in its recently

1157 filed subsequent comments, the commenter argues t hat the use of t he categories of 1158 “direct food use” and “indirect food use” “create s the potential for almost all 1159 antimicrobials to be considered as possibly leaving residues on food.” (ACC attachment 1160 1 , identified in the docket at ; by document ID number EPA-HQ-OPP.2008-0110-0108, p. 1161 4 ) ). However, EPA adopted the categories of dire ct and indirect food use as a way to 1162 tier data requirements for residue chemistry and toxicology, not to expand the category 1163 of food uses. For a use to qualify as an indire ct food use it must result in residues in 1164 food and EPA clearly has the aut hority under FIFRA and the FFDCA to request data on 1165 and assess the risk of pesticide residues in fo od. Despite the commenter’s claims to 1166 the contrary, it is not EPA’s intent to use this data requirements rule as a basis for 1167 expanding what antimicr obial uses qualify as direct or in direct food uses. Accordingly, 1168 EPA’s economic analysis has accurately capt ured the costs imposed by this rule. 1169 5. Comment on lack of final guidelines. Finally, commenters argued that 1170 reproposal was needed because affected parti es cannot properly evaluate the data 1171 requirements without final guidelines on how su ch studies should be conducted. 1172*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 48 of 233 6. EPA’s response on lack of final guidelines. EPA disagrees with this comment: 1173 EPA can require submission of a particular study even if no guideline has been 1174 provided. The types of data needed for EPA to make a registration decision are clearly 1175 identified in its proposed rule. Testing laboratories routinely conduct these studies, as 1176 evidenced by the test cost data which was available for use in both EPA’s and the 1177 commenter’s economic analyses. Final guidelines are available for the majority of tests 1178 required, and draft guidelines provide informa tion for the applicant to consider. Since 1179 there was an understanding of the types of data EPA proposed to require, the 1180 commenter had sufficient information to co mment on whether EPA had asked for the 1181 data needed for determining whether pesticides meet the relevant statutory safety 1182 standards. 1183 It is important to keep in mind that, as noted in the proposed rule, new part 158, 1184 subpart W is “retaining most current data requ irements for antimicrobi als. . . and revises 1185 other existing data requirement s.” (73 FR 59383) The guidelines that the commenter 1186 asserts as not providing sufficient information to permit meaningful comment pertain, for 1187 the most part, to these exis ting data requirements that ar e not being modified by this 1188 rulemaking. As to the “ new” data requirements that are imposed by this rule, the 1189 commenter has not specifically explained why interested parties cannot meaningfully 1190 comment on these requirements or why a final guideline is needed to provide 1191 meaningful comments on these studies. In fact, as to these “new” studies, OPPTS 1192 guidelines are available for all except the nat ure of the residue on su rfaces study. For 1193 that study, due to the many site - and chemical specific variat ions, a protocol review is 1194 required. 1195 This commenter later filed additional comments stating that “FIFRA requires EPA 1196 to issue test guidelines.” (ACC/CSPA letter , identified in the docket at ; by document ID 1197*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 49 of 233 number EPA-HQ-OPP.2008-0110-0107, p. 4). In accordance with FIFRA section 1198 3(c)(2)(A), EPA has promulgat ed data requirement rules “specifying the kinds of 1199 information which will be required to support the registration of a pesticide.” EPA is not 1200 required to issue guidance explaining how st udies that are addressing the data required 1201 under the regulations should be perform ed. Additional information on EPA’s 1202 development of guidelines is in Unit XX. 1203 C. Alternative Testing Paradigms. 1204 1. Comment. A commenter asked how OPP plans to implement the National 1205 Academy of Sciences (NAS)/EPA Visi on of Toxicity Testing in the 21 st Century or the 1206 Strategic Plan for Evaluating the Toxicity of Chemicals. The comm enter noted that the 1207 rule should be specific in identifying alte rnative approaches that EPA will consider. 1208 2. EPA’s Response. In the proposed rule, in Unit XVIII, entitled “Alternative 1209 Testing Paradigms,” EPA discussed its commitm ent to moving towards a more efficient 1210 and refined testing/risk assessment paradigm fo r antimicrobial pesticide chemicals. That 1211 discussion included the following: 1212

 OPP’s current thinking on how Struct ure-Activity-Relationships (SAR) and 1213 Quantitative SAR (QSAR or (Q)SAR) modeling could be used as part of an integrated 1214 approach to hazard and risk assessment to support a regulatory decision-making 1215 process for antimicrobial pesticides. 1216

 The evolution of the cu rrent paradigm of animal ( in vivo ) toxicity testing 1217 toward a more integrated tiered testing approach for antimicrobial pesticides. 1218

 Development of computational tools fo r interpreting data from computational 1219 chemistry, high-thr oughput screening (HTS) and genomic technologies. 1220*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 50 of 233  The EPA-funded reports by the NAS entit led “Toxicity Testing for Assessment 1221 of Environmental Agents” (2006) and “Toxicity Testing in the 21 st Century: A Vision and 1222 a Strategy” (2007). 1223 The NAS recommendations are truly visionary and involve a transformative 1224 paradigm shift in toxicology based largely on the increased use of in vitro molecular and 1225 cellular assays, and computati onal modeling that make test ing faster and less costly, 1226 and reduces animal testing significantly. T he new technologies are expected to help 1227 EPA better understand how chemicals perturb no rmal biological function(s), and thus 1228 identify toxicity pathways. Potential toxic effects of chemicals could then be predicted 1229 based on in vitro bioactivity profiles derived from a chemical’s effects on cellular 1230 molecules and processes. Thus, the scient ific foundation for th is new paradigm is 1231 based on linking in vitro effects with adverse outcomes in vivo , and on computer 1232 modeling that extrapolates to predicted responses in whole tissues, organisms and 1233 populations based on realistic hum an or environmental exposures. 1234 EPA is working to develop and evaluate new technologies in molecular, cellular, 1235 and computational sciences to supplement or replace the more traditional methods of 1236 toxicity testing and risk assessment (see http://www.epa.gov/pesticides/science/testing1237 assessment.html ). Such an approach begins with consider ation of exposure information 1238 along with hazard-based hypotheses about the pl ausible toxicological potential of a 1239 chemical or group of chemicals based on t heir physical-chemical properties and their 1240 effects on biological targets in vitro . This information is then combined with computer 1241 modeling to target animal testing to the specific data needed for human health and 1242 ecological risk assessments. 1243 No single new technology will be able to address all situations. However, by 1244 using a suite of tools and approaches in co mbination, EPA believes it is possible to 1245*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 51 of 233 improve the hazard and exposure assessment s that form the basis for understanding 1246 pesticide chemical risks. It will take time and substantial research to build this new 1247 approach. OPP will incorpor ate the new technologies into EPA’s hazard and risk 1248 assessment processes as the technologie s are sufficiently developed and peer 1249 reviewed. Development and vetting of this new approach to chemical management 1250 must be accomplished while continuing to make pesticide registration decisions. 1251 Eventually, the new technologies should: 1252

 Create a broader suite of computer-ai ded methods to better predict potential 1253 hazards and exposures, and to focus testing on likely risks of concern. 1254

 Improve the approaches to more traditional toxicity tests to minimize the 1255 number of animals used while expanding t he amount of information obtained. 1256

 Improve OPP’s understanding of toxicity pathways to allow development of 1257 non-animal tests that better predict how ex posures relate to adverse effects. 1258

 Improve the diagnostic biomonitoring and surveillance methods to detect 1259 chemical exposures and identify causes of toxic effects. 1260 Since the publication of the proposed rule in October 2008, OPP announced its 1261 strategic direction to move toward an im proved testing and assessment paradigm where 1262 in vivo (animal) testing would be targeted to t he most likely hazards of concern. OPP 1263 envisions an enhanced testing/assessment paradigm that is a progressive, tiered1264 testing approach. This paradigm shift s hould accrue the following benefits to OPP: 1265

 Ability to evaluate more chemicals ac ross a broader range of potential effects 1266 in a shorter time frame. 1267

 Potential to increase the feasibility of assessing the risks posed by mixtures. 1268

 Enhanced predictive ability to determine whether animal testing is needed to 1269 refine a risk assessment and to inform management decisions. 1270*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 52 of 233  Refine and reduce animal testing by maximizing information obtained from 1271 animal studies, and focusing on effects of concern. 1272

 Opportunities for improved diagnostic biomonitoring and surveillance methods 1273 to detect chemical exposures and i dentify causes of toxic effects. 1274

 Enhance the quality and efficiency of risk assessment and risk management 1275 decisions. 1276 Over the next several y ears, OPP intends to impr ove and transform its approach 1277 to pesticide risk management by enhancing it s ability to use integrated approaches to 1278 testing and assessment. The Agency’s wo rk on an integrated approach means the 1279 development of increasingly effective labor atory animal tests t hat are designed to 1280 maximize the information generated about the nat ure of the effects being studied. OPP 1281 intends to expand its toolbo x of predictive models. The new toxicity and exposure 1282 approaches will enhance priority-setting and screening approaches and therefore focus 1283 Agency and societal resources on those c hemicals with the greatest risk potential. 1284 These advances will be incorporated wit hin a risk assessment framework of 1285 problem formulation, hazard, dose re sponse, exposure assessment, and risk 1286 characterization to support pesticide registrati on decisions. As this framework evolves, 1287 EPA will create pilot programs and develop guidance documents to inform applicants 1288 and others of the alternat ive approaches being used. 1289 It will require many years to realize the NAS vision of a new toxicity paradigm 1290 based on evaluating perturbations in cellula r pathways by reliance on an array of 1291 computational and in vitro methods. However, the development and expansion of 1292 certain tools used to guide more intelligent in vivo testing is anticipated to become 1293 available in the nearer term ( ≤ 5 years) which includes (Q )SAR/expert systems, TTCs, 1294 and in vitro technologies. As EPA transitions to the use of t hese components of 1295*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 53 of 233 intelligent testing or alternative methods, communication will be essential. Through its 1296 Pesticide Program Dialog Co mmittee, OPP has created a 21 st Century Toxicology/New 1297 Integrated Testing Strategies Wo rkgroup. For information, see 1298 http://www.epa.gov/pesticides/ppdc/testing/index.html

. 1299 Additionally, OPP has and wi ll continue to publicly vet this new approach. On 1300 May 24 – 26, 2011, OPP request ed that the FIFRA Scientif ic Advisory Panel (SAP) 1301 consider and revise a set of scientific issues related to Integrated Approaches to Testing 1302 and Assessment (IATA) Strategies: Use of new computational and molecular tools. 1303 OPP plans to build on an established foundation of using a variety of tools in a tiered 1304 testing and assessment framework by systematically adding new tools and 1305 methodologies, as well as an advancing u nderstanding of key events in toxicity 1306 pathways. OPP requested the SAP's input on EPA ’s plans to maximize use of existing 1307 data from similar compounds, including in formation from new toxicity hazard 1308 computational and in vitro predictive models, and exposure modeling to target in vivo 1309 toxicity testing that is necessary to a ssess and manage chemical risks, appropriately. 1310 Two case studies illustrated the us e of these approaches. The SAP Report , once 1311 completed, will be is available at 1312 http://www.epa.gov/scipoly/sap/meet ings/2011/052411meeting.html#frn. 1313 VI. Discussion of Key Comments on Antimicrobial Use Patterns 1314 A. Definitions of Use Patterns 1315 1. Comment . The commenter suggested diffe rent use patterns for EPA to 1316 consider. The commenter believes that t he use patterns proposed by EPA are not use 1317 patterns but descriptions of product types. The commenter suggested six general use 1318 patterns for EPA to consider. These include: 1319

 Indoor industrial (all nonfood); 1320*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 54 of 233  Indoor residential/commerci al/institutional nonfood; 1321

 Indoor commercial/institutional food; 1322

 Aquatic areas nonfood; 1323

 Aquatic areas food; 1324

 Material preservative for exempt treated article uses. 1325 2. EPA’s response. The Agency disagrees that these suggested use patterns 1326 are adequate substitutes for the proposed us e patterns. The use patterns that EPA 1327 proposed provide a reasonable approach for allowing the Agency to more clearly 1328 identify and tailor the data requirements for the different type of antimicrobial pesticides. 1329 In some cases, that is best accomplished by using the product type to define the use 1330 pattern. 1331 EPA has reviewed the commenters’ descrip tions of their six suggested general 1332 use patterns and has determined that they do not acknowledge all potential exposure 1333 pathways of antimicrobial pesticides, particula rly those discharged to wastewater as a 1334 result of processing and end-use. Alt hough three of the proposed general use patterns 1335 include “indoor” in the name, t he exposure potential for thes e use patterns is not limited 1336 to the indoor environment. This is becaus e these patterns include processes and end1337 uses of antimicrobial pesticides that are discharged to wastewater, thereby leading to 1338 the potential for microorganisms in WWTPs to be exposed to antimicrobial pesticides 1339 and for aquatic organisms to be exposed to antim icrobial pesticides in surface water 1340 downstream of WWTPs. If the antimicrobial is not completely removed during 1341 treatment, exposures of humans to antim icrobials may also be associated with 1342 antimicrobials discharged to wastewater t hat enters WWTPs and subsequently enters 1343 surface water via WWTP effluents. Further more, there may also be the potential for 1344*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 55 of 233 terrestrial organisms and humans to be expos ed to antimicrobial pesticides if the 1345 antimicrobial that is discharged to wa stewater partitions to biosolids. 1346 Since the processing or end-use of an antim icrobial pesticide in an indoor setting 1347 does not preclude the potential for its re lease to ambient environmental media, 1348 particularly under circumstances in whic h there is potential for discharges of 1349 antimicrobial pesticides to wastewater , EPA believes that the designation of an 1350 antimicrobial use pattern s as “indoor” is misleading. Based on the conclusion that 1351 processing or end-use of an antimicrobial pesticide in an indoor setting does not 1352 preclude its release to the ambien t environment, EPA believes that a down

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- drain 1353 analysis is needed for all use patterns with the exception of the aquatic areas use 1354 pattern. 1355 The commenter’s suggested use pattern s are also inconsistent with EPA’s 1356 reevaluation re-evaluation of the data required for wood pres ervatives. In response to 1357 comments, the Agency determined that all treated wood needs to be considered as 1358 having the potential to come into contact with surface water. Therefore, for wood 1359 preservatives, EPA has changed several data requirements in both the environmental 1360 fate table and the non-target organisms table from “CR” to “R.” However, under the 1361 commenter’s six suggested use patterns, w ood preservatives would be considered to 1362 be the same as material preservatives: The commenter did not differentiate the data 1363 needed between the two use patterns. EPA bel ieves that the data needed for a wood 1364 preservative is distinctly di fferent from that needed for a materials preservative. Wood 1365 preservatives have a high potential for envir onmental exposure, as evidenced by both 1366 environmental fate and nontarget organisms data requirements that ar e “R.” Material 1367 preservatives have a lower potential for env ironmental exposure and consequently are 1368 “CR.” Thus, the data requirements codified today in this final rule acknowledge the 1369*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 56 of 233 differences in the data needed by having two di stinctly different use patterns: Wood 1370 preservatives and material preservatives. 1371 Given the inclusion of the term “indoo r” as part of the title of three of the 1372 suggested use patterns, and the combining of wood preservatives and materials 1373 preservatives into a single use pattern, EPA believes that the six general use patterns 1374 suggested by the commenter (see above) would not adequately serve EPA’s or the 1375 public’s needs. Additionally, the 1997 review by the FIFRA Scientific Advisory Panel 1376 (SAP) of EPA’s 12 antimicrobial use pattern s indicated the SAP’s agreement that the 1377 Agency’s proposed designation of 12 use pa tterns was a reasonable approach to 1378 organizing data requirements, an d was, in fact, similar to the approaches used by 1379 Canada’s Pest Management Regulatory Agency (PMRA), and the California 1380 EPA

. Environmental Protection Agency. Therefore, EPA is codifying the 12 use patterns 1381 that were proposed. 1382 B. Wood Preservative Use Pattern 1383
1. Comment. Several commenters questioned how wood preservatives were 1384 treated in the proposed rule. One comment er thought that all wood preservatives 1385 should be considered as having contact with wa ter. Another comm enter argued that the 1386 industrial, commercial and do-it-yourself uses of wood preservatives are different and 1387 should be assessed differently. 1388
2. EPA’s response. Wood preservatives are pesticides for incorporation into 1389 wood products to control wood degradati on problems due to fungal rot or decay, 1390 sapstain, molds, or wood-destroying insects. 1391 As explained in the proposed rule, (73 FR 59405) EPA’s current practice of 1392 determining the data required for a wood preservative product is dependent upon where 1393 the product is intended to be used (land-only ve rsus land and aquatic). Under this 1394*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 57 of 233 approach, fewer environmental fate and ecolog ical effects studies are required for 1395 products that limit their use patterns to l and-only uses. This approach also assumes 1396 that diversion does not occur and that wood that is treated for land-only uses does not 1397 end up in the water and vice versa. EPA specifically requested comments on the 1398 regulation of wood preservative products, and indicated that based on the comments 1399 received could determine to continue with the cu rrent practice of considering land-only 1400 applications, or change to a land and aquatic usage. Based on comments indicating 1401 that the data required to regi ster a wood preservative should not differentiate between 1402 land only and aquatic only applications of treated wood, EPA has re-evaluated this 1403 approach. As discussed in the proposed rule, it is difficult to assure that diversion does 1404 not occur. EPA consider ed three possibilities: 1405

 Assume all treated wood could have t he potential to come into contact with 1406 surface water. 1407

 Use an approach similar to that advo cated by the American Wood Protection 1408 Association (AWPA) approach which diffe rentiates between marine/freshwater and 1409 ground contact use/above ground contact use. 1410

 Maintain status-quo. 1411 Wood preservatives used to protect wood st ructures placed directly in or over 1412 water (e.g., marine pilings, docks) will leach active ingredient into the water, resulting in 1413 potential exposure of aquatic organisms. Wo od preservatives used in the terrestrial 1414 environment for uses such as fences, siding, and decks will leach active ingredient into 1415 soil where it may be transported into t he aquatic environment and expose aquatic 1416 organisms. 1417 The Emission Scenario Document (ESD) for Wood Preservatives prepared by 1418 the Organization for Economic Co-operation and Development (OECD) as part of its 1419*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 58 of 233 Series on Emissions Scenario Documents pr ovides guidance on how to estimate 1420 emissions of chemical substances in wood pr eservative products to air, water, and soil 1421 as a result both of product application and storage of treated wood prior to shipment 1422 and treated wood-in-service. This OECD ESD documents the occurrence of pathways 1423 of release of chemical substances during wo od preservative application to facility drains 1424 that subsequently convey wastewater to WW TPs; entry of chemical substances to 1425 adjacent surface water bodies by way of r un-off water from unpaved storage of wood 1426 preservative-treated products following a rain event; and leaching of chemical 1427 substances from in-service uses of treat ed exterior wood out of ground (i.e., fences, 1428 noise barriers), wood in-ground (transmission poles, fence posts), and wood in direct 1429 contact with fresh and sea water (poles and planks/decking of jetties and wharfs). 1430 Additional information on indire ct releases to surface wate r of antimicrobial pesticides 1431 used as wood preservatives can be found in response to comment 134.1 in the 1432 Response to Comments Document in the docket at http://www.regulations.gov

. 1433 Given the number of pathwa ys identified, that result in potential exposure from 1434 treated wood, the Agency determined that all treated wood should be considered as 1435 having the potential to come into contact with surface water. All wood preservative risk 1436 assessments will now be performed consideri ng that the treated wood could end-up 1437 either on the land or in the aquatic environment. As previously discussed, there are 1438 multiple pathways for wood preservative degr adates and/or leachates to reach surface 1439 water. The AWPA approach wo uld have continued the practice of determining the data 1440 requirements based on the intended use site of the treated product. 1441 Given this decision, that all treated w ood could have the potential to come into 1442 contact with surface water, t he wood preservative columns of the final Environmental 1443 Fate and the Nontarget Organisms Tables were revised. 1444*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 59 of 233 For the final Environmental Fate Table, for the wood preservatives column, the 1445 data requirements for anaerobic soil met abolism, aerobic aquatic metabolism, and 1446 anaerobic aquatic metabolism were changed from “CR” to “R.” Because treated wood 1447 products have outdoor usages, the Agency bel ieves that these products have the 1448 potential to come into contact with surface water as well as soils which can become 1449 flooded or waterlogged and then be rel eased to surface water. 1450 For the final Nontarget Or ganism Table, for the wood preservatives column, the 1451 data requirements for chronic to xicity testing with fish (f ish early-life stage) and aquatic 1452 invertebrate (aquatic invert ebrate life-cycle) are being c hanged from “CR” to “R” to 1453 provide chronic data when chr onic exposure is expected. 1454 The Agency agrees that the industrial, commercial , and do-it-yourself uses of 1455 wood preservatives are different in terms of human exposure. Industrial wood 1456 preservative uses are assessed for those work ers involved in the act ual treatment of the 1457 wood with the preservative. This includes op erations at a pressure treatment facility 1458 where workers add the preservative to tr eatment cylinders, remove treated wood 1459 charges from the cylinders, c heck the treated wood to verify retention rates, and move 1460 the freshly treated wood around t he facility (from cylinder to drip pad to storage to 1461 shipping). Industrial sapstain wood preserva tives are also assessed at the treatment 1462 facility for the application of t he pesticide. Worker tasks fo r the non-pressure treatment 1463 (non-PT) are slightly different than those at pressure treatment (PT) facilities. Separate 1464 exposure measurements unique to each type of treatment (PT vs non-PT) are used in 1465 the assessments. 1466 Exposures to commercial and do-it-yourse lf uses of treated wood are assessed 1467 for those installing the treated wood and for those exposed to the treated structures 1468 (e.g., play sets and decks). 1469*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 60 of 233 VII. Discussion of Key Comment s on General and Administrative Issues 1470 A. Scientific Advisory Panel (SAP) Waivers 1471 1. Comment. A commenter noted that in t he preamble to proposed part 158, 1472 subpart W, EPA cites multiple SA P reports that did not specif ically mention antimicrobial 1473 pesticides. Therefore, the co mmenter believes these SAP reviews were insufficient. 1474 Another commenter noted that it has been 9 years since the last SAP review and that 1475 EPA should request another SAP review prior to implementation of proposed part 158, 1476 subpart W. Still another commenter believes that EPA’s request that the SAP waive its 1477 review of proposed part 158, subpart W bas ed on the SAP’s 1997 review was improper, 1478 and that the SAP cannot waive it s statutory review obligation. 1479 2. EPA’s response. EPA disagrees with the comments. On June 3, 1997, EPA 1480 presented an early version of the part 158, subpart W proposal in an open meeting to 1481 the SAP. At that time , the SAP provided extensive comments in five areas: Toxicology, 1482 residue chemistry, ecological effects and environmental fate, human exposure, and 1483 efficacy. Since then, the SAP has considered m any specific studies and scientific issues 1484 included in proposed part 158, subpart W as par t of their reviews of guidelines and of 1485 data requirements for conventiona l agricultural pesticides (see references 30, 31, 32, 1486 33, and 34 to the proposed rule). the documents identified in the docket by document ID 1487 numbers EPA-HQ-OPP-2008-01 10-0032, -0033, -0034, -0035, and -0036). In 1997, the 1488 SAP also noted its concern about the possibl e effects of antimicrobials on WWTPs. 1489 Partially in response to the SAP comments, EPA proposed a tiered set of environmental 1490 fate data requirements that will allow the Agency to better characterize potential 1491 incidences of antimicrobials in su rface waters, as a result of down

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- drain uses of 1492 antimicrobials. 1493*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 61 of 233 When the Agency prepared to propos e 40 CFR part 158, subpart W, EPA 1494 requested that the SAP waive its review of the about-to-be-proposed part 158, subpart 1495 W because there were no new scientific issu es. The SAP waived its review of the 1496 about-to-be proposed part 158, subpart W on February 19, 2008. The Agency 1497 continues to believe that there are no new scientific issues that warrant additional 1498 review by the SAP. EPA’s request for an a SAP waiver for the fi nal antimicrobial data 1499 requirements rule is discussed in Unit XXIV. FIFRA section 25 requires EPA to give the 1500 SAP at least 60 days to review proposed regulations and 30 days to review final 1501 regulations. However, the SAP can det ermine to waive its review during the statutory 1502 time periods. 1503 B. Risk Assessments for Wood Preservatives. 1504 1. Comment . A commenter noted that Canada’s PMRA and USEPA conduct risk 1505 assessment for wood preservatives different ly. EPA’s risk assessment is based on the 1506 treated wood when used at the final use site , while the PMRA’s risk assessment is 1507 based at the site where the wood is treated. The PMRA also does not distinguish 1508 between terrestrial-only or aquatic-only use for anti-sapstains and heavy-duty wood 1509 preservatives. 1510 2. EPA’s response . The Agency acknowledges differences between its risk 1511 assessment of wood preservatives and that of Canada’s PMRA. As previously 1512 discussed in Unit VI.A , ., EPA has re-evaluated its approach for determining the data 1513 required for a wood preservative product. As part of the re-evaluation, EPA considered 1514 the human and ecological risks based on exposu re pathways identified in OECD’s ESD 1515 for Wood Preservatives. This ESD identif ies potential human and ecological exposures 1516 from both treatment of wood at processing facilities and in-service uses on land and in 1517 water. The Agency determined that all treat ed wood should be considered as having 1518*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 62 of 233 the potential to come into contact with surfac e water. This determination reflects EPA’s 1519 concern about the potential for the indire ct release to surface waters of wood 1520 preservatives. As a result, EPA is changi ng its approach to requiring environmental and 1521 ecological effects studies for wood pres ervatives. All wood preservative risk 1522 assessments will now be performed consideri ng that the treated wood could end-up 1523 either on the land or in t he aquatic environment, thus incr easing harmonization between 1524 PMRA and EPA with regard to wood preservatives. 1525 D. C. Clarity on How and When CR Data is Required 1526 1. Comment. A commenter asked EPA to specif y criteria to determine whether 1527 a data requirement is “R” (Required) or “CR” (Conditionally Required). According to the 1528 commenter, the discussion of “R” and “CR” s uggests that a data requirement labeled 1529 “CR” may not be required to be addressed by the applicant. A second commenter 1530 stated that it is unclear how and when conditionally required data are triggered. Another 1531 commenter asserted that data requirement s should be waived only under extraordinary 1532 circumstances, and that the use of waiver s can effectively preclude appropriate 1533 regulation of the pes ticide under FIFRA. 1534 2. EPA’s response . In its proposed data require ment tables, EPA specified 1535 whether a data requirement is “Required”, “Cond itionally Required”, or “Not Required” 1536 based on how likely the study is needed to comple te an assessment of an antimicrobial 1537 pesticide. As a rule of thumb, a “required” study is likely to be needed 50 percent of the 1538 time or more and a “conditionally requir ed” study is likely to be needed less than 50 1539 percent of the time. Typically, a “conditiona lly required” study is triggered based on the 1540 results of a study that has already been conducted. Triggers in the test notes indicate 1541 the circumstances under which the Agency has learned through experience that the 1542 information is needed. In many instances, the applicant would be able to make the 1543*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 63 of 233 determination that the trigger has been met and should include the data in their original 1544 submission. In other cases, EPA will make the determination based on its review of 1545 submitted data and would then request add itional data from the applicant. EPA 1546 encourages applicants to consult with the A gency to determine the actual need for the 1547 data. 1548 All data requirements must be addressed by the applicant by either conducting 1549 the study or submitting information that coul d fulfill the data requirement, such as citing 1550 open literature or other data sources, or by requesting and receiving a data waiver. 1551 EPA grants data waiver requests only on a case-by-case basis and only when the 1552 available evidence indicates a particular stud y is not needed or that there are particular 1553 reasons for not conducting the study. For exam ple, if the physical/chemical properties 1554 of the chemical did not lend themselves to the testing procedure, such as performing an 1555 inhalation study with a chemical that is a solid and has an extremely low vapor 1556 pressure, then a waiver might be granted. EPA also grants waivers in exceptional 1557 circumstances, for instance, if a test substanc e is so corrosive that animal studies would 1558 cause undue pain and suffering. 1559 VIII. D iscussion of Key Comments on Product Chemistry 1560 The following represent the signific ant comments received on the need for and 1561 evaluation of product chemistr y studies as proposed by EPA. 1562 A. Application of Subpart D Product Chemistr y Data Requirements to Antimicrobials

. 1563 1. Comment . A commenter requested that EPA pr ovide adequate justification for 1564 applying the existing product chemistry data r equirements for conventional pesticides to 1565 antimicrobials without cons ideration of the highly dissimilar chemistries and 1566 inapplicability of many of the requirements. 1567*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 64 of 233 2. EPA’s response . It has been EPA’s longstanding practice to require product 1568 chemistry data. Product chemis try data are required to ident ify the chemicals used to 1569 manufacture a product and to understand the ph ysical and chemical properties of the 1570 ingredient or product. Such information is generally independent of the intended use 1571 pattern. Product chemistry data are used during label development to identify 1572 information to be included on the label, su ch as the flammability statement, and 1573 directions for disposal of the product. Hence, despite any differences between 1574 conventional and antimicrobial pesticides, t he Agency believes it is appropriate to apply 1575 the same product chemistry data requirem ents to antimicrobials as required for 1576 conventional pesticides. The guidelines fo r conducting product chemistry studies offer 1577 flexibility to account for differ ences between chemical classes. 1578 B. Lack of Adequate Opportunity for Review of Product Chemistry Data Requirements 1579 1. Comment . One commenter asserted that registrants of antimicrobial 1580 pesticides were not given the opportunity to review and comment on conventional 1581 pesticide data requirements that are now be ing proposed for antimicrobial pesticides. 1582 2. EPA’s response.

. In the preamble to propos ed part 158, subpart W, EPA 1583 proposed to apply the product chemistry data r equirements for conventionals in 40 CFR 1584 part 158 subpart D to antimicrobial pesticides. Therefore, during the public comment 1585 period for the proposed part 158, subpart W, from October 8, 2008, to April 6, 2009, any 1586 interested party could have commented on t he product chemistry data requirements in 1587 subpart D (which have been in place si nce October 2007) and their potential 1588 applicability to antimicrobials. 1589 I X

. Discussion of Key Comments on IX. Product Performance Data Requirements 1590*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 65 of 233 The following represent the signific ant comments received on the need for and 1591 evaluation of product perform ance studies as proposed by EPA. Changes from the 1592 proposed rule to the final rule are also described. 1593 A. Product Performance Guidelines 1594 1. Comment. Several commenters shared thei r belief that EPA was seeking to 1595 avoid comment on the product performance data requirements in the proposed rule by 1596 stating that the Agency ” “ is not proposing to revise product performance data 1597 requirements” at this time . Another commenter asked how the product performance 1598 section of the proposed rule could be finalized without the 810 guidelines? 1599 2. EPA’s response . The proposed product performance data requirements table 1600 contained referenced the older 91 series guidelines. As stated in the proposed rule , the 1601 requirements being proposed were “nearly identic al” to the existing data requirements in 1602 § 158.400 and 161.640, and the tabl e was “transferred essent ially unchanged” (73 FR 1603 59391). Since the 2008 proposed rule, EPA published the draft 810 guidelines for 1604 comment. four of the 810 series guide lines (810.2000, 810.2100, 810.2200, and 1605 810.2300 for sterilants, disinfectants and sanitizers) were published for comment in the 1606 Federal Register for public comment on of January 27, 2010 (75 FR 4308)

. 4380) 1607 (FRL 8437-2), indicating that these guidelines represent the Agency’s current 1608 recommendations for conducting product perform ance studies to support antimicrobial 1609 pesticide label cla ims. That Notice of Availability announced that the 810 guidelines 1610 series would be incorporated into the final rule for antimicrobial data requirements 1611 regulation : As announced . Three additional product perfo rmance guidelines (810.2400, 1612 810.2500, and 810.2600) published for public comment on September 15, 2011 (76 FR 1613 57031) (FRL 8879-1). Thus , in addition to commenting on the draft guidelines 1614*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 66 of 233 themselves, commenters had an opportunity to comment on the inclusion of the 810 1615 series in the Product Performance Data Requirements table. 1616 The availability of the final guidelines fo r sterilants, disinfectants and sanitizers 1617 (810.2000, 810.2100, 810.2200, and 810. 2300) was announced in the Federal 1618 Register of March 16, 2012 (77 FR 15750) (FRL 9332–4), and for the three additional 1619 product performance guidelines (8 10.2400, 810.2500, and 810. 2600) in the Federal 1620 Register of June 27, 2012 (77 FR 38280) (FRL 9349-5). 1621 In this final rule , EPA is replacing the 91 series designations proposed in the part 1622 158, subpart W product perform ance table with the appropriate 810 series guideline 1623 numbers and names. Thus, commenters had an opportunity to comment on the 1624 inclusion of The 810 series in the final Product Performanc e Data Requirements table. 1625 Three additional guidelines represent the Agency’s current recommendations for 1626 conducting product performance guidelines (810.2400, 810. 2500, and 810.2600) should 1627 be published for comment in a timeframe similar to that of publication of the final rule for 1628 Antimicrobial Data Requirements. studies to support antimicrobi al pesticide label claims. 1629 See Unit XVIII

. for a discussion on guidelines. 1630 B. Emerging Pathogens 1631 1. Comment . A commenter asked why there is no formal regulatory practice for 1632 registering products to address public he alth emergencies or emerging pathogens 1633 promptly and effectively? 1634 2. EPA’s response . EPA does not believe that the promulgation of a rule dealing 1635 with data requirements is the appropriate place to address emerging pathogens. A 1636 major consideration in the Agency's proc ess for addressing public health emergencies 1637 and emerging pathogens is to work closely with the Centers for Disease Control and 1638 Prevention (CDC), Department of Agriculture ( USDA ) , , and FDA, as appropriate, to 1639*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 67 of 233 provide a timely and accurate response to t hese situations. Under FIFRA section 18, 1640 the Agency also has authority to grant certain exemptions fr om the provisions of FIFRA 1641 and also to approve the use of unregister ed pesticides when emergency conditions 1642 exist. Additionally, in April 2008, the Agency implemented a disinfection hierarchy 1643 policy for addressing emerging viral pathogens. In formation on this policy is available on 1644 the EPA website at http://www.epa.gov/oppad001/disinfection_hier.htm. EPA believes 1645 that emerging pathogens requi re flexibility and speed in disseminating information and 1646 seeks to address such situations in a prompt and effe ctive manner. 1647 C. Definitions of Sanitizer and Disinfectant 1648 1. Comment . Several commenters claimed that the proposed definitions do not 1649 reflect the work done by the regulated comm unity in cooperation with EPA since 1999. 1650 In particular, these comment ers did not agree with the proposed definitions of sanitizer 1651 and disinfectant. 1652 2. EPA’s response . Since the publication of the proposed rule, the definitions, 1653 including those for sanitizer and di sinfectant, were published in the Federal Register for 1654 public comment on January 27, 2010, as part of requesting comment on draft guideline 1655 810.2000. After further review of the comments submitt ed on the proposed definition for 1656 disinfectant and sanitizer, the Agency has revised the definitions that had been 1657 proposed for both part 158, subpart W and the 810 Guidelines. EPA believes that the 1658 definitions being codified today in part 158, subpart W reflect the input received from the 1659 regulated community in multiple submissions. The definitions for sanitizer and 1660 disinfectant will be the same in both part 158, subpart W and in the 810 Guidelines. 1661 The definition for disinfectant is bei ng revised from, “Disinfectant means a 1662 substance, or mixture of substances that des troys or eliminates a specific species of 1663 infectious or public health microorganism, but not necessarily bacterial spores, in the 1664*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 68 of 233 inanimate environment” to r ead, “Disinfectant means a s ubstance, or mixture of 1665 substances, that destroys or irreversibly inac tivates bacteria, fungi and viruses, but not 1666 necessarily bacterial spores, in the inanimate environment.” 1667 The definition for sanitizer is being revi sed from, “Sanitizer means a substance, 1668 or mixture of substances that reduces the bacterial populatio n in the inanimate 1669 environment by significant numbers, but does not destroy or eliminate all bacteria or 1670 other microorganisms” to read, “Sanitizer means a substance, or mixture of substances 1671 that reduces the bacterial population in t he inanimate environment by significant 1672 numbers, (e.g., 3 log 10 reduction) or more, but does not destroy or eliminate all bacteria. 1673 Sanitizers meeting Public Health Or dinances are generally used on food contact 1674 surfaces and are termed sanitizing rinses.” A 3 log 10 reduction is the minimum log 1675 reduction needed to make a non-food contact su rface sanitizing label claim, and is 1676 considered a significant reduction. 1677 The definitions for fungicide, steril ant, tuberculocide and virucide are being 1678 revised to include the following ph rase: “or mixture of subst ances.” Inclusion of this 1679 phrase in all of the definitions in § 158.2203 for types of produc ts that bear public health 1680 claims (excepting microbiological water purif ier) means consistency in the definitions 1681 and an acknowledgement that t he destroying, reducing, or inactivating may be 1682 accomplished via more than a single substanc e. Also, this makes these definitions 1683 similar to the FIFRA section 2(u) definition of pesticide which also contains the phrase 1684 “or mixture of substances.” 1685 Additionally, the definition for virucide is being revised to include the word 1686 irreversibly, as follows: “Virucide means a substance, or mixture of substances, that 1687 destroys or irreversibly inactivates viruse s in the inanimate environment,” thus reading 1688 similar to the definition for t uberculocide. Additionally, the definition for sterilant will be 1689*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 69 of 233 revised to remove the second sentence of the pr oposed definition: “For purposes of this 1690 subpart, ‘sporicide’ and ’sterilant’ are synonymous.” EPA no longer requires that 1691 products that make sporicidal clai ms also make sterilant claims. 1692 D. Nonpublic Health Data and Claims 1693 1. Comment . A commenter asked t hat the issue of when to generate efficacy 1694 data for nonpublic health products be discussed, since registrants are required to 1695 develop data to substantiate label claims. 1696 2. EPA’s response . The Agency believes this issue has been addressed in § 1697 158.2220 "Product Performance," which clearl y states, "Each appli cant must ensure 1698 through testing that his product is effica cious when used in accordance with label 1699 directions and commonly accepted pest control practices.” However, to clarify the issue 1700 further, the Agency is adding a definition fo r nonpublic health claims that will appear as 1701 40 CFR 158.2204(b): 1702 Nonpublic health claim . An antimicrobial pesticide is considered to 1703 make a nonpublic health claim if the pesticide product bears a 1704 claim to control microorganisms of economic or aesthetic 1705 significance, where the presence of the microorganism would not 1706 normally lead to infection or disease in humans. Examples of 1707 nonpublic health claims include, bu t are not limited to, algaecides, 1708 slimicides, preservatives and products for which a pesticidal claim 1709 with respect to odor sources is made. 1710 1711 Additionally, EPA is revising 40 CFR 158.2220(c)(3) to read: 1712 (3) Product performance data for each product that bears a 1713 nonpublic health claim. Each product that bears a nonpublic 1714 health claim, as described in §158.2204(b), must be supported by 1715 product performance data. Each registrant must ensure through 1716 testing that his product is efficacious when used in accordance 1717 with label directions and comm only accepted practices. The 1718 Agency reserves the right to require, on a case-by-case basis, 1719 submission of product performanc e data for any pesticide product 1720 registered or proposed for registration or amendment. 1721 1722 Also, EPA has posted on the Antimicrobials Division website the parts of the 91 1723 Guideline series that apply to testing of nonpublic health products. Although these 1724*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 70 of 233 guidelines are from 1982, they are still relied on to develop data to support label claims 1725 for nonpublic health label claims products . EPA acknowledges that some of the 1726 references in the 1982 guideli nes are to the older 91 series guidelines , which is being 1727 replaced by the 810 series guidelines . To assist readers, EPA has also posted a cross1728 walk table so readers can locate the appl icable section of the 810 Guidelines. For 1729 information, see http://www.epa. gov/oppad001/non-public-health.html. 1730 X. Discussion of Key Comments on Toxicology Data Requirements 1731 The following represent the signific ant comments received on the need for and 1732 evaluation of toxicology studies as proposed by EPA. Changes from the proposed rule 1733 to the final rule are also described. 1734 A. TTC A. Threshold of Toxicological Concern Approach 1735 1. Comment . There should be a threshold of to xicological concern (TTC) type of 1736 approach for antimicrobials. 1737 2. EPA’s response. OPP’s Antimicrobials Division is aware of the TTC concept , 1738 and in conjunction with

. ILSI , is currently pursuing the deve lopment of an application of 1739 the TTC concept to evaluate antimicrobial pesticides. At t his time, EPA anticipates a 1740 time frame of 2 to 3 years for development. Once a TTC

- based approach has been 1741 developed and piloted, then EPA would cons ider when/if the approach should be 1742 included in part 158 , subpart W Development and peer review of a TTC approach for 1743 antimicrobials is expected to occur over the next 1 to 2 y ears. Based on expert peer 1744 review and public comment, the Agency will make decisions regarding implementation

. 1745 B. Test Note to Neurotoxicity Studies 1746 1. Comment . A commenter stated that proposed test not e 6 to the proposed 1747 toxicology table in § 158.2230 triggering th e neurotoxicity studies is contradictory and 1748*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 71 of 233 unclear. The commenter asked how the abs ence of a neurotoxicity screen in the 90- 1749 day oral rodent study would impact proposed test note 6? 1750 2. EPA’s Response. Proposed test note 6 specifie s that if t he neurotoxicity 1751 screen that occurs in the 90-day oral r odent study or any other data demonstrate 1752 neurotoxic effects, then bot h the acute neurotox icity study and the 90-day neurotoxicity 1753 study are triggered. For certain use patte rns with the potential for larger exposures 1754 (most notably food exposures), all three of these studies are in itially required. 1755 According to proposed test note 8 to the pr oposed toxicology table in § 158.2230, the 1756 applicant may combine the 90-day oral toxici ty study and the 90-day neurotoxicity study 1757 by adding a separate group of test animals. 1758 However, for some use patterns, the 90- day oral study is r equired, and the other 1759 two studies are conditionally required, bei ng triggered by proposed test note 6. EPA 1760 acknowledges that when only the 90-day oral study is re quired, an applicant is at a 1761 disadvantage in terms of any chance for combining the 90-day neur otoxicity study with 1762 the oral study: Once the 90-day oral study with its neurotoxicity screen has been 1763 performed, and neurotoxic effects are identified, then it is not possible to add a separate 1764 group of test animals to t he already conducted study. 1765 As a point of clarification, EPA is adding a new test note to the final Toxicology 1766 Table in § 158.2230(g) to clarif y that the neurotoxicity screen that is part of the 90-day 1767 oral study is not equivalent to a 90-day neurot oxicity study. If the 90-day oral toxicity 1768 study does not have a neurotoxicity screen, then the acute neurotoxicity study in the rat 1769 would be required. The new test note also in cludes: “if the 90-day oral rodent study 1770 does not include a neurotoxicity screen, th en the acute neurotoxicity study will be 1771 required.” As part of renum bering, this new test note is now test note 11 to the 1772 Toxicology Table in the final rule , § 158.2230(g )

. ) in this final rule,. 1773*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 72 of 233 C. End-Product Use-Dilution Toxicity Testing 1774 1. Comment. Several commenters stated th eir belief that acute end product 1775 use-dilution toxicity testing should be opt ional and requested greater clarification on 1776 when to test a diluted product. The comment ers asked whether ex trapolation from the 1777 active ingredient or as-sold acute toxicity testing is acceptable? Another commenter 1778 claimed that requiring end-product six-pack testing of one or more dilutions is 1779 duplicative. 1780 2. EPA’s response. Proposed test note 2 to the proposed toxicology table in § 1781 158.2230, specifies how to conduct acute toxici ty testing for end-use products (EP). EP 1782 testing is conducted on the product as formula ted for sale and distribution. From the EP 1783 acute toxicity studies, EPA derives toxicity categories which are then used to determine 1784 the precautionary labeling stat ements on the product. However, it is common for some 1785 products to be diluted before being used. The use-dilution testing is in addition to the 1786 as-formulated-for-sale testing since there are exposures to both. Ac ute toxicity testing 1787 on the product that has been diluted-for-use supplies the information needed to derive 1788 precautionary statements for the user of the product. EPA is revising proposed test 1789 note 2 to make this clearer. 1790 D. The Phrasing “limited portion of the human lifespan” 1791 1. Comment . Several commenters asked EPA to identify the criteria to 1792 determine “repeated human exposure over a lim ited portion of the human life span.” 1793 They asked EPA to specifically describe what the phrase “human exposure is not 1794 purposeful” means? 1795 2. EPA’s response . Proposed test note 11 to the proposed toxicology table in § 1796 158.2230, specifies the triggers that would r equire the performance of a 90-day oral 1797 study in the non-rodent. EPA has re-evaluat ed this test note and decided to remove 1798*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 73 of 233 test note 11 from proposed part 158, subpart W. Proposed test note 11 ( , subparagraph 1799 i )

. contained the phrase “repeated human exposur e over a limited portion of the human 1800 life span.” EPA agrees that this phrase is not useful. Proposed test note 11 ( , 1801 subparagraph ii )

. contained a trigger for any indi rect food use that would have been 1802 considered to be a “low exposu re.” Given the restructuring of the final Toxicity Data 1803 Requirements Table, i. e., the shift away from using hi gh and low exposure as the table 1804 headers to a food/nonfood approach, test notes 11 (

. i )

. and 11 (

. ii )

. are no longer needed. 1805 In the final Toxicity Table in § 158.2230(g), the data required for an indirect food-use is 1806 specified directly (in the table header) and a tr igger is not needed. As discussed in Unit 1807 X.B , proposed ., test note 11 as proposed is replaced by a different test note as part of 1808 re-numbering in this final rule

. 1809 Proposed Test note 12 to the proposed to xicology table in § 158.2230, 1810 specifies three triggers that would require t he performance of a 21/28-day dermal study. 1811 EPA has also re-evaluated test note 12 and agrees that the phrases “repeated human 1812 exposure over a limited portion of the human life span” and “human exposure is not 1813 purposeful” are not useful. Accordingly, EPA has decided to remove the first two of the 1814 triggers. Therefore, revised the 21/28 day dermal study trigger. The 21/28 day dermal 1815 study is now triggered if all of the following criteria are met: 1) the intended use of the 1816 antimicrobial pesticide product is expected to result in repeated dermal human exposure 1817 to the product , ; 2) data from a subchronic 90-day dermal toxicity study are not 1818 available , ; 3) and the 90-day dermal toxicity st udy has not been triggered (the third 1819 proposed trigger). 1820 E. Mouse Carcinogenicity Study 1821 1. Comment. According to several comment ers, the mouse carcinogenicity 1822 study does not provide useful informati on, and is, in fact, not suited for 1823*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 74 of 233 determining/extrapolating human carcinogeni city. They contended that EPA should no 1824 longer require the mouse carci nogenicity study. This would also mean that there is no 1825 need for the mouse range-finding study. 1826 2. EPA’s response . The issue regarding the us efulness of the mouse for 1827 carcinogenicity testing is one that is curr ently under debate by th e OPP. Currently, 1828 carcinogenicity testing, whether for conventional pesticides under § 158.500 or for 1829 antimicrobials under part 158, subpart W requires testing in two rodent species. 1830 However, OPP is currently conducting a comprehensive anal ysis of its rodent chronic 1831 bioassay database to document the utility of the mouse bioassay for both cancer risk 1832 assessment and Reference Dose (RfD) derivat ion for non-cancer endpoints. When this 1833 analysis is completed, a recommendation wi ll be made regarding the testing needed for 1834 cancer hazard identification. OPP anticipates completing this analysis during 2012

. 1835 Once OPP’s internal review process is comp lete, then it is likely that EPA would solicit 1836 review and comment by the FIFRA SAP. If at a later date, the determination is made to 1837 alter the carcinogenicity data requirement s, then appropriate changes would be 1838 proposed to be made to data requirements and r egulations pertaining to conventionals, 1839 biochemicals and microbials, and antim icrobials through rulemaking. 1840 F. Ames Assay 1841 1. Comment . A commenter argued that the Am es assay should not be required, 1842 because it is inappropriate for antimicrobials that kill bacteria. 1843 2. EPA’s response . It is recognized that the Am es assay may not be useful for 1844 assessment of mutagenic potential of antimicrobial pesticides, as this test uses strains 1845 of bacteria as the primary te st material, and antimicrobials are designed to kill, among 1846 other things, bacteria. So, the bacteria may be killed before mutagenic effects are 1847 demonstrated. However, for some antimic robial pesticides, the Ames assay has 1848*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 75 of 233 already been conducted and if the Ames assa y was conducted at levels that do not 1849 cause toxicity to the bacterial strains test ed, then the study may be acceptable to fulfill 1850 the reverse mutation as s ay requirement. However, if an Ames assay has not yet been 1851 conducted for a particular antimicrobial, then, t he Ames assay should not be conducted. 1852 In this final rule, test note 32 for the reverse mutation assay requirement to in the final 1853 Toxicology Table in § 158.2230(g), is revis ed to allow reliance on previously-conducted 1854 Ames tests when the bacteria strain was not killed, but to state a preference for assays 1855 such as an in vitro mammalian cell assay, (e.g., the mous e lymphoma TK +/- assay). 1856 G. Dermal Absorption Studies 1857 1. Comment . A commenter argued that EPA should accept in vitro skin 1858 penetration data. According to the comment er, accepting such data would harmonize 1859 with requirements in the Eur opean Union (EU) and elsewhere. The commenter pointed 1860 to well-established OECD guidelines for thes e studies. The commenter also asserted 1861 that proposed test note 37 to the proposed toxi cology table in § 158.2230, addressing 1862 the requirement for a dermal absorption st udy, should not apply to corrosive/irritant 1863 products. 1864 2. EPA’s response . The Agency has, on a case-by-case basis, used in vitro 1865 dermal absorption studies to determine the m agnitude of dermal absorption of pesticide 1866 chemicals. However, the Agency has not adopted an official policy of using only in vitro 1867 data to support these decisions. The OECD guideline 428, while describing an in vitro 1868 method for dermal absorption, does not rule out the use of in vivo data along with in 1869 vitro data to determine dermal absorption. Further , the test guideline notes that formal 1870 validation studies of the in vitro method have not been performed. 1871 The Agency is working on developing a more formal policy that would use both in 1872 vivo and in vitro dermal penetration data in a weight -of-evidence (WOE) determination 1873*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 76 of 233 in appropriate cases. The Agency would always consider QSAR or other models, 1874 submitted in support of the determination of de rmal absorption. The decision to accept 1875 such information is the Agency’s, based on it s review and evaluation of the submission. 1876 Proposed Test note 37 to the proposed toxicol ogy table in § 158.2230, specifies 1877 that the trigger for requiri ng a dermal penetration study ar e the results from a risk 1878 assessment “assuming that derma l absorption is equal to oral absorption.” This means 1879 that EPA assumes 100 percent dermal absorpti on. If a subchroni c dermal study and/or 1880 dermal absorption data are not available, then a risk assessment could be conducted 1881 using the default assumption of equivalent abs orption by the dermal and oral routes of 1882 exposure. If unacceptable risks are found, then either the subchronic dermal study or a 1883 dermal absorption study would be required. EPA recognizes that the assumption of 100 1884 percent dermal absorption is conservative; however, this assumption would only be 1885 used in the absence of an acceptable derma l subchronic study or dermal absorption 1886 data. In this final rule, test note 37 to t he Toxicology Table in § 158.2230(g), is revised 1887 to clarify this process. EPA also agrees that corrosive/irritant products should not be 1888 tested in dermal absorption studies. Therefore, test note 3 to the Toxicology Table in § 1889 158.2230(g), which specifies that testing is not needed for corrosive materials, is added 1890 as a trigger for not requiring the dermal absorption study. 1891 H. Tiering 1892 1. Comment. One commenter ar gued that EPA has not provided meaningful 1893 tiering for its toxicology requirements for antimicrobials. Anot her commenter claimed 1894 that exposure alone is not an appropriate crit erion to use for a tiered testing scheme, 1895 that both exposure and risk shoul d be considered. A third co mmenter asserted that the 1896 high and low human exposure categories for to xicity are not appropriate and suggested 1897*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 77 of 233 that a tiered scheme such as that used for environmental fate data requirements would 1898 be more appropriate. 1899 2. EPA’s response. EPA disagrees with these comments. In its proposed rule 1900 EPA proposed a tiered testing scheme for to xicology testing that was based on the 1901 amount of exposure as defined by use patte rns. Based on its experience in conducting 1902 risk assessments, EPA understands which use patterns have exposures of higher 1903 duration and magnitude, and therefore coul d have greater risks. Use patterns with 1904 higher exposures require more submission of more data than use patterns with lower 1905
exposures. 1906 I. Guideline Numbers in CFR the Code of Federal Regulations 1907 1. Comment. A commenter stated t hat the final rule should not specify a 1908 guideline number. Instead, the data requirement tables should describe the endpoint in 1909 question, and the information needed for EPA’s risk assessment. OPP could develop 1910 guidance that could be placed on the web. 1911 2. EPA’s response

. EPA agrees with this comment. The guideline number 1912 column could be removed from the table. Instead, EPA could have an internet page 1913 that describes multiple met hods of fulfilling the data require ments. An internet table 1914 could be updated faster to reflect newer techniques than rulemaking to revise a 1915 regulation in the CFR. However, there is al so value in having the guideline number in 1916 the CFR, which then shows the av ailable guidelines relevant to the particular study that 1917 should be considered in addressing the requi rement. EPA has made no decision on 1918 whether or not to initiate a rulemaking to remove all the guideline numbers from the data 1919 requirement tables in 40 CFR part 158. The t ables finalized in subpart W in this rule 1920 include guideline numbers. 1921 J. Animal Testing 1922*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 78 of 233 1. Comment. A commenter requested that E PA specifically state in its 1923 regulations that non-animal methods are a cceptable for fulfilling a data requirement. 1924 The commenter argued that the Draize study (the acute ey e irritation study) in rabbits 1925 should be eliminated. 1926 2. EPA’s response . Non–animal test methods are c ontinually being examined for 1927 use in fulfilling the toxicology data require ments that are used to assess the hazard of 1928 pesticide chemicals. However, in order for non-animal approaches to be used for 1929 fulfilling toxicology data r equirements, these approaches mu st first be scientifically 1930 validated to ensure that they are as good as the existing test method for predicting 1931 hazard and also assessed to determine whether they meet the Agency’s “3 R” goals of 1932 reduce, refine, and replace the use of animals in testing. With re spect to antimicrobial 1933 pesticides, the Agency has started to explor e such approaches. One example of this is 1934 the voluntary pilot program for eye irritati on testing of antimicrobial pesticides using 1935 non–animal test methods, found at http://www.epa.gov/oppad001/eye-irritation.pdf. 1936 K. Derivation of 200 Parts per Billion Criterion 1937 1. Comment . A commenter asked whether the 200 parts per billion (ppb) level 1938 used as the dividing line between high and lo w human exposures is the concentration of 1939 a substance in an adult’s daily food consumption? 1940 2. EPA’s response. The derivation of the 200 ppb level was previously 1941 established by FDA for indirect food use biocides , and is described in the proposed rule 1942 (73 FR 59394, October 8, 2008). (Also, see document 10 (identified in the docket at 1943 http://www.regulation.gov

. ) As discussed in the proposed rule, by document ID number 1944 EPA-HQ-OPP-2008-0110-0010). FDA derived the 200 ppb is derived level by dividing 1945 FDA’s the cumulative exposure upper limit of 1000 ppb level for food contact substances 1946 by 5 to account for the fact that antimicrobial pesticides (e .g., biocides) are a class of 1947*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 79 of 233 pesticide that are generally toxic by design. The 200 ppb level is the concentration of 1948 the antimicrobial residues in or on the food item. EPA is using 200 ppb as a delineation 1949 consistent with the FDA’s toxicology reco mmendations for food contact substances. 1950 Therefore, those indire ct food uses that have residues that are less than or equal to 200 1951 ppb in or on the food item usually have fe wer data requirements than those that have 1952 residues that are greater than 200 ppb in or on the food item. For clarity, the following 1953 information concerning the 200 ppb level and it s derivation from FDA levels has been 1954 added to § 158.2230(d): 1955 The 200 ppb level was original ly used by the Food and Drug 1956 Administration with respect to the concentration of residues in or 1957 on food for tiering of data requi rements for indirect food use 1958 biocides. The Agency has also adopted this same residue level for 1959 determining toxicology data require ments for indirect food uses of 1960 antimicrobial pesticides. The 200 ppb level is the concentration of 1961 antimicrobial residues in or on the food item. 1962 1963 L. Use of OECD Guidelines for EPA Registrations 1964 1. Comment . A commenter asked EPA to cons ider incorporating the following 1965 OECD guidelines into the new part 158, s ubpart W to reduce the number of animals 1966 killed in LD 50 tests: OECD guidelines 436; Acute I nhalation Toxicity - Acute Toxic Class 1967 Method, and revised 223; Avian Acute Oral Toxicity Test, and Short Guidance on the 1968 Threshold Approach for Acute Fish Toxicity. 1969 2. EPA’s response . OPP does not have a policy for use of OECD 436 for acute 1970 inhalation toxicity. If a study conducted a ccording to OECD 436 were submitted for the 1971 purpose of assessing acute inhalation toxicity , EPA would review and accept the results 1972 if the study were conduct ed in an acceptable manner and provided sufficient information 1973 to fulfill the data requirement. Similarly, if a study conducted according to OECD 223 or 1974 the Threshold Approach, were submitted, then EPA would review the study and then 1975*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 80 of 233 make a determination on whether the study was conducted in an acceptable manner 1976 and provided sufficient information to fulfill the data requirement. 1977 M. Alternative Formats for Toxi cology Data Requirements Table Suggested by 1978 Commenters 1979 1. Comment . In the comments submitted to EPA, the commenters suggested 1980 two alternative toxicity data requirement approaches for EPA to consider. Alternative 1981 approach 1 was organized in paragraphs and alternative approach 2 was in a table 1982 format similar to that proposed by EPA. 1983 2. EPA’s response . The commenters provided two alternative approaches for 1984 toxicology data requirement s for antimicrobials. As stated by the commenter, 1985 alternative approach 1 was “intended to provide clearer instructions to registrants,” 1986 attempted “to fully incorporat e the new science” of integrat ive approaches to testing, 1987 and included “a threshold concept for to xicological concerns.” (ACC Comment , 1988 identified in the docket at http://www.regulations.gov ; by document ID numberEPA-HQ1989 OPP-2008-0110-0088.6; Appendix E, entitled “Comments on Proposed Data 1990 Requirements for Toxicology” p. 24). The commenter did not provide to EPA the same 1991 or similar table-type of format used for par t 158 data requirements. There were no test 1992 notes to define the triggers fo r moving from tier to tier. The commenter acknowledged 1993 that their suggested alternative approach 1 woul d require “expert scientific judgment” (p. 1994 25), and also discussed that EPA in the proposed rule ( 73 FR 59423) that EPA had 1995 indicated the need for to develop scientific position papers, and recommendations for 1996 internal and external review of integrative approaches . EPA considers alternative 1997 approach 1 to be a dramatic departure fr om EPA’s proposal, and agrees with the 1998 commenter that certain scientific issues may not be ready for codification. EPA does 1999 not believe, at this time, that this approac h meets the needs of t he Agency, or has any 2000*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 81 of 233 advantages over the table format. EPA found the paragraph explanations unclear. As 2001 acknowledged by the commenter, the paragraph format would result in a more complex 2002 decision tree that would require a signific antly greater amount of interpretation and 2003 consultation when compared to the existing t able formats. There would be a significant 2004 learning curve for both EPA and those mem bers of the public that have become 2005 accustomed to data requirement t ables such as in part 158. Within this response, EPA 2006 has responded to alternative approach 1 in totality. EPA notes that the individual 2007 scientific issues raised wit hin the paragraphs are addressed separately, as they were 2008 separated into the various disciplinary ar eas of the toxicol ogy comments. 2009 EPA has also evaluated alternative approach 2. This alternative approach is in a 2010 table-type of format with a strict split between food and nonfood uses. The test notes 2011 developed by the commenters are extremely detailed and contain information that EPA 2012 believes is more appropriate in guidance. However EPA has used the suggested test 2013 notes to revise its proposed testnotes the test notes in this final rule as appropriate. For 2014 example, the commenters’ s uggested test note 32 to the in vivo cytogenetics study is 2015 clearer than EPA’s proposed test note 34. Therefore EPA is revising test note 34 to the 2016 final Toxicology Table in § 158.2230(g), accordingly

. 2017 As discussed previously, as a result of comments received, EPA is no longer 2018 using the terms “high human exposure” and “l ow human exposure” as proposed for the 2019 antimicrobial toxicology data r equirements table. Instead, in the final rule, EPA is now 2020 using a food/nonfood approach with so me similarities to that of the toxicology data 2021 requirements table for conventional pestici des to distinguish the use patterns with 2022 higher exposure that need more toxicity data from those that need less. Accordingly, 2023 the table headers for the Toxicology Data Requi rements Table in the final rule are: 2024 “Direct Food Uses;” “Indirect Food Uses (>200 ppb);” “Indirect Food Uses ( ≤ 200 ppb);” 2025*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 82 of 233 “ Swimmers Swimming Pools , Aquatic Areas, Wood Preser vatives, Metal Working 2026 Fluids;” and “All Other Nonfood Uses.” 2027 Unlike conventional pesticide chemical s, a strict food/nonf ood use “split” for 2028 delineating data requirements is not appropriate for antimicrobial chemicals. Such an 2029 approach does not fully address the unique use patterns for antimicrobials, most 2030 specifically, those involving indirect food us es. As a result of comments received, EPA 2031 decided to employ a modification of the food/nonfood approach to delin eate the specific 2032 data requirement needs for antimicrobial pesticides. 2033 The commenter has also asked that EPA include within subpart W a new § 2034 158.2235 which would be analogous to 40 CF R 158.510 for conventional chemicals 2035 (Tiered Testing Options for Nonfood Use Pest icides). EPA does not believe this is 2036 needed for antimicrobials. Once it has been determined that the use is nonfood, then 2037 certain of the nonfood use scenarios require the submission of more data, and certain 2038 require the submission of less data. As specified in the column headings for Nonfood 2039 Uses, swimming pools, aquatic areas, wood pr eservatives, and metal working fluids 2040 require a particular set of data. All other nonfood uses require less data. Thus, the 2041 tiering is already built into the appr oach used for antimicrobials. 2042 XI. Discussion of Key Comments on Nontarget Organism Data Requirements 2043 The following represent the signific ant comments received on the need for and 2044 evaluation of nontarget organi sm studies as proposed by EPA. Changes from the 2045 proposed rule to the final rule are also described. 2046 A. Need for Ecotoxicity Data for Indoor Uses 2047 1. Comment . Several commenters argued that there are few ant imicrobial use 2048 patterns where ecological effects informati on would be relevant to an assessment under 2049 FIFRA because there is no expect ation of environmental exposure

. 2050*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 83 of 233 2. EPA’s response. As explained in the proposed rule, there is now a greater 2051 concern regarding indoor uses of antimic robials because those uses can lead to 2052 environmental exposure when they go down

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- drain. The Agency and the scientific 2053 community have more recently become concerned with pharmaceuticals and personal 2054 care products (PPCPs), which are now rec ognized as environmental contaminants. A 2055 subset of these PPCPs includes antimicr obial pesticide products, some of which are 2056 being detected in various environmental co mpartments/media [e.g., surface water and 2057 WWTP biosolids]. As discussed in the propos ed rule (73 FR 59407), these findings are 2058 notable, because many of t he antimicrobial pesticides de tected are registered for only 2059 indoor use patterns. 2060 There are many uses for which a high potential for environmental exposure 2061 exists, especially outdoor uses such as wood preservatives, ballast water treatments, 2062 antifoulant paints and coatings, aquatic areas, and others. These uses may require a 2063 more extensive data set that could include acute and chronic tests in both freshwater 2064 and saltwater, and possibly in the sediment as well as the water column. If the effluent 2065 from a WWTP is likely to contain an antimicr obial pesticide, or if the antimicrobial is 2066 likely to partition to the sludge that is deriv ed during the treatment process, then indoor 2067 uses could require additional testing to fu rther characterize the hazard and the risk. 2068 A. Transformation Products 2069 1. Comment. Several commenters question ed, how a registrant would 2070 determine if “transformation pr oducts” would need to be tested ?

. With regard to the 2071 criteria for when testing is required on transformation products, another commenter 2072 stated the ir belief that any data developed to a ssess the potential risk to nontarget 2073 organisms should be developed with the appropriate residue of concern (ROC) (i.e. 2074 degradation product, metabolite, or TGAI) rather than always te sting with the TGAI. Still 2075*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 84 of 233 another commenter asked how would EPA det ermine that the transformation products 2076 are “more toxic, persisten t, bioaccumulative or have been shown to cause adverse 2077 effects in mammalian or aquatic reproductive studies ?” .” Finally, a commenter 2078 requested that EPA should explain what is considered “s table” in the environment in 2079 proposed test note 3 to the proposed nont arget organism table in § 158.2240. 2080 2. EPA’s response. The Agency evaluates the need for nontarget organism 2081 testing of transformation products on a case-b y-case basis, using several sources of 2082 information, which includes, most important ly, environmental fate data. EPA proposed 2083 to require nontarget organism testing of transformation/degr adation products or 2084 leachate residues in proposed § 158.2240(a)(3) and (4). To respond to this comment, 2085 EPA also considered a similar comment on transformation/degradation products or 2086 leachate residues for environmental fate testing (see Unit XIV.B ). .). In response to 2087 these comments, EPA determined to clarify and revise the criteria for testing of 2088 transformation/degradation pr oducts and leachate residues for nontarget plant and 2089 organisms, and environmental fate, (§ 158.2250(b), (§§ 158.2240(a)(3 ), ) and 2090 158.2280(a)(2)) to read as follows: 2091 Data on transformation/degradation products or leachate residues 2092 of the parent compound are also requi red to support registration, if 2093 the Agency determines that the 2094 transformation/degradation/leachate products meet one of the 2095 following criteria: 2096 (i) More toxic, persi stent, or bioaccumulative than the parent, 2097 (ii) Have been shown to cause adverse effects in mammalian or 2098 aquatic reproductive studies, or 2099 (iii) The moiety of concern (i.e., functional group in the parent 2100 chemical molecule that imparts adverse effects) remains intact. 2101 For nontarget plant protection (158. 2250(b)) EPA determined to revise the 2102 criteria to read as follows: 2103 (b) Data on transformation/degradat ion products or leachate residues 2104 of the parent compound are also r equired to support registration, if 2105*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 85 of 233 the transformation/degradat ion/leachate products meet 2106 one of the follo wing criteria: 2107 (1) More toxic, persistent, or bioaccumulative than the parent, 2108 (2) Have been shown to cause adverse effects in mammalian or aquatic 2109 reproductive studies, or 2110 (3) The moiety of concern (i.e., functional group in the parent chemical 2111 molecule that imparts adverse effects) remains intact. 2112 As explained in Unit XIV.B ., environmental fate studies provide information on 2113 the stability and persistence of the active ingredient and degradation products in the 2114 various environmental media. If the environ mental fate studies on the parent indicate 2115 the transformation/degr adation product(s) is, for example, more persistent in soils, then 2116 it is possible that nontarget plants or animals could be exposed to the degradate. Once 2117 the transformation products and the environmental compartment in which they occur are 2118 identified, then the availabl e toxicology data (e.g., r eproduction tests, developmental 2119 tests, non-rodent chronic studies) are reviewed to determine toxicity. 2120 After reviewing all available information, then EPA would use these criteria to 2121 determine if ecological effects data on the transformation/degradation products or 2122 leachate residues are required for either nont arget organisms or no ntarget plants. EPA 2123 believes that nontarget plant protecti on data may sometimes be needed when the 2124 Agency begins conducting species-spec ific endangered species assessments for 2125 antimicrobial pesticides. 2126 EPA does not use the term “residue of c oncern (ROC)” in the final Nontarget 2127 Organisms Data Requirements Tabl e. Instead, the appropriate test material(s), such as 2128 TGAI, degradate, or TEP, is specified in the data requirements table in § 158.2240. 2129 This approach is also used for the convent ional nontarget organism table in part 158. 2130 Generally, for ecological testing, the TGAI testing is performed first, and then additional 2131 testing on a transformation product may be required based on the process described 2132 above previously . Depending on how fast a substanc e decays, a nontarget organism or 2133*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 86 of 233 plant could actually be exposed to a mixture of the parent and one or more 2134 degradation/transformati on products. 2135 C. Test Note 7 to the N ontarget Organism Table and Wood Preservatives 2136 1. Comment. Proposed Test note 7 to the propos ed nontarget organism data 2137 requirements table in § 158.2240 specifies t he triggers for requiring typical end-use 2138 product (TEP) testing for the acute freshwater invertebrate study and acute freshwater 2139 fish study. A commenter asked whether, even though, the wood preservatives use 2140 pattern is specified as “NR,” could the TEP testing be required because of the triggers in 2141 test note 7. 2142 2. EPA’s response. Proposed test note 7 also triggered the testing for the TEP 2143 acute estuarine and marine organi sms toxicity testing. EPA agr ees that the combination 2144 of “R”s, “CR”s, “NR”s and the cu rrent structure of proposed test note 7, is confusing and 2145 that clarificati on is needed. 2146 The data requirements for TEP test ing and proposed test note 7 was also 2147 considered in light of the Agency’s recent determination based on comments received 2148 (see Unit VI.B ) .) on EPA’s current practice of conducting risk assessments for wood 2149 preservatives based on land-only versus a land and aquatic predetermined use pattern. 2150 All wood preservative risk assessments will now be performed considering that the 2151 treated wood could end-up either on both the land or in the aquatic environment. As 2152 previously discussed, there are multiple pathways for wood preservative degradates 2153 and/or leachates to reach surface water. EPA has also determined to conduct a down

- 2154 the

- drain assessment for all appropriate us e patterns which would include wood 2155 preservatives, and antifoulant pai nts and coatings (see Unit XV.A ). .). For wood 2156 preservatives, these determinations mean that additional ecological testing is required 2157*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 87 of 233 to conduct an ecological risk assessment, an d the following changes are made to the 2158 wood preservative testing column: 2159

 Acute freshwater invertebrates toxici ty (TEP testing): change from “NR” to 2160 “CR”; 2161

 Acute freshwater fish toxicity (T EP testing): change from “NR” to “CR”; 2162

 Acute estuarine and marine organisms to xicity (TEP testing): change from 2163 “NR” to “CR”. 2164 For antifoulant paints and coatin gs, the determination to conduct a down

- the

2165 drain assessment also means that additi onal data could be needed for the Down

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- 2166 drain assessment, and the following change s have been made to the antifoulant paints 2167 and coatings testing column: 2168

 Acute freshwater invertebrates toxici ty (TEP testing): change from “NR” to 2169 “CR”; 2170

 Acute freshwater fish toxicity (T EP testing): change from “NR” to “CR”; 2171

 Acute estuarine and marine organisms to xicity (TEP testing): change from 2172 “NR” to “CR”. 2173 EPA believes that simplifying the data requi rements that reference test note 7 to 2174 the final Nontarget Organism Table in § 158.2240(c) so that these requirements are CR 2175 for all use patterns is clearer, and also closer to the suggestions made by the 2176 commenter s in their suggested nontarget organi sm data requirements table. Their 2177 suggested table was predominantly “CR” for aquatic uses. Theref ore, in this final rule, 2178 test note 7 triggers the “CR” studies. 2179 However, changing all the use patterns to “CR” for the TEP studies means 2180 changing the “R” proposed for the aquatic use, and industrial processes and water 2181 systems use patterns for the acute freshwater invertebrates toxicity study and the acute 2182*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 88 of 233 freshwater fish toxicity study , to “CR.” To account fo r this change proposed test note 7 2183 to the proposed nontarget organism t able in § 158.2240 has been revised in the final 2184 rule to include an additional trigger ( see § 158.2240(d) test note 7 (

. iv )) : ). Data are 2185 required when “the end-use antim icrobial product will be applied directly into an aquatic 2186 environment.” EPA believes that the implications of this tr igger are equivalent to the 2187 “R” and essentially this is a non-c hange. These changes are summarized below here for 2188 both the aquatic areas and industrial proc esses and water systems testing column: 2189

 Acute freshwater invertebrates toxici ty (TEP testing): change from “R” to 2190 “CR”; 2191

 Acute freshwater fish toxicity (T EP testing): change from “R” to “CR”; 2192

 Acute estuarine and marine organisms to xicity (TEP testing): no change. 2193 Nontarget organism toxicity testing of the TEP should be infrequently required for 2194 the antifoulant paints and coatin gs use pattern because for this use pattern, the TEP 2195 could be the paint. Because the testing for a quatic organisms is done in water, the test 2196 material must be soluble in water, or made soluble by addition of an appropriate solvent, 2197 if one exists, or other appropriate mechanical methods. Paint is not soluble and there 2198 may not be a way to make it soluble. Sinc e these studies are oft en run in glass aquaria, 2199 the paint could coat the sides of the glass and the test animals themselves. The paint 2200 could ruin test equipment by clogging lines and injection nozzles. Therefore EPA has 2201 added a new test note 5, whic h is replacing proposed test note 5 to the proposed 2202 nontarget organism in § 158.2240. New test note 5 to the final Nontarget Organism 2203 Table in § 158.2240(c) states that an applic ant should request a waiver if the TEP 2204 cannot be tested. 2205 EPA also notes that a test note specif ying the number of species to be tested 2206 was omitted in the proposed rule for the TEP te sting for acute freshwater fish toxicity. 2207*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 89 of 233 This test note is needed for clarity. Test note 3 to the final N ontarget O rganism T able in 2208 § 158.2240(c) has been added to the line for acute freshwater fish toxicity. Test note 3 2209 to the final Nontarget Or ganism Table in § 158.2240(c) has been added to the line for 2210 acute freshwater fish toxicity. Instead of “g reater than 1 ppm or 1 mg/L” as indicated in 2211 the proposed rule, the toxicity trigger has been corrected to read “less than or equal to 1 2212 ppm or 1 mg/L.” If the LC 50 is greater than 1 ppm this m eans that chemical tested was 2213 moderately to practically non-toxic on an acute basis. If the LC 50 is less than 1 ppm this 2214 means that chemical tested was highly to very highly toxic on an acute basis and would 2215 have a serious adverse affect(s) on the organi sm tested at low concentrations. For 2216 clarity, in test note 3 to t he Nontarget Organism Table, EPA has corrected the draft final 2217 rule to ensure that we codify the appropriate trigger (less t han or equal to) to indicate 2218 that testing is needed for chemicals that dem onstrate high to very high toxicity on an 2219 acute basis. 2220 D. Acute and Chronic Toxicity Data 2221 1. Comment. A commenter argued that it is essential to have both acute and 2222 chronic toxicity test results for at least one freshwater invertebrate, vertebrate, and plant 2223 species, and at least one marine/estuarine invertebrate, vertebrate, and plant species. 2224 2. EPA’s response. EPA proposed to require acute tests for both a coldwater 2225 and warmwater freshwater fish, an invertebr ate, and one or more aquatic plants. For 2226 marine/estuarine species, for most use pat terns, EPA proposed to conditionally require 2227 acute testing with a fish and two aquatic invert ebrate species, including a bivalve, when 2228 the Agency believes there is a potential for the active ingredient or a potentially toxic 2229 degradate to reach the estuarine/marine envir onment through transport (e.g., leaching, 2230 runoff) from the treatment site . In such a situation, chr onic testing with one or more 2231 marine/estuarine species also may be requi red if the Agency bel ieves that chronic 2232*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 90 of 233 exposure is likely. These studies also ar e required for those uses where the pesticide 2233 product is applied directly into the marine/estuarine environment. 2234 As to chronic testing , EPA proposed to require the fish early life stage and the 2235 aquatic invertebrate life-cycle studies for the industrial processes and water systems 2236 (once-through), antifoulant coat ings and paints, and aquatic areas use patterns. At that 2237 time, EPA also proposed to conditionally re quire the same two studies for the low 2238 environmental grouping (now called the all other use patterns category) and wood 2239 preservatives. 2240 However, based on this and other comments, EPA has re-evaluated the 2241 nontarget organism data needed for a regist ration decision and concluded that 2242 additional acute and chronic data are needed. See Units V.B , ., X.C , ., and XIV.F

. for 2243 discussions on the rationale for and descriptions of the changes. 2244 EPA does not require chronic testing for plants. Plant species encompass 2245 many different life spans. Phytoplankton reproduce quickly and have extremely short 2246 life spans. Annuals live for 1 year. Many perennials do not actually live for multiple 2247 years, but reproduce from seeds year after year. The plant species that live the longest 2248 would be woody species, such as trees. EPA does not believe that antimicrobial use 2249 patterns impact terrestrial areas such t hat chronic exposures occur: To EPA’s 2250 knowledge, no adverse chronic effects to terrestrial plants caused by pesticides have 2251 been documented on plants. Any effect on terrestrial plant species has been 2252 categorized as an acute effect and would be covered by current testing procedures. 2253 Chronic effects of aquatic plants are covered by the acute aquatic testing guidelines. 2254 Algae is are used as the primary test species for evaluating effects to the acute testing of 2255 aquatic plants. The testing is based on gr owth parameters and t he tests normally run 2256 for periods of time that woul d include several generations of the algae. The results from 2257*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 91 of 233 the acute these algal studies , while only conducted over a few days, would be similar to 2258 those obtained from chronic test ing in other species, and c w ould be used to assess any 2259 chronic effects to aquatic plant species. 2260 D. Avian Studies 2261 1. Comment . In proposed test note 4 to t he proposed nontarget organism table 2262 in § 158.2240, which triggers the avian diet ary study, EPA specified a trigger of 100 mg 2263 ai/kg (milligrams active ingredient/kilogra m) for additional testing. A commenter 2264 requested information on why this trigger was selected. The commenter also claimed 2265 that EPA could use exposure tools to conduc t an initial assessment based on Tier 1 2266 data, and then trigger additional testing based on risk. 2267 2. EPA’s response . OPP has long used this value as an indication of toxicity to 2268 birds. As specified in 40 CFR 156.85(b )(3), any pesticide (including conventional 2269 pesticides) that is intended for outdoor use with an avian acute oral LD 50 of 100 mg 2270 ai/kg or less requires a precautionary label statem ent that the pesticide is toxic to birds. 2271 EPA believes that if 100 mg ai/kg is approp riate to trigger a precautionary label 2272 statement, then it is al so appropriate to use as a trigger for testing. T herefore, if the 2273 avian oral acute toxicity study indicates an oral LD 50 of 100 mg ai/kg or less, then an 2274 avian dietary study is required. 2275 In the proposed rule, for the avian diet ary toxicity study, EPA proposed to require 2276 testing on two species for the aquatic areas and to conditionally require testing on one 2277 avian species for all of the other use pa tterns. The comments reviewed and evaluated 2278 by EPA on avian toxicity testing included t he commenter’s suggested data requirements 2279 table for nontarget organisms, which specified “CR” for all avian testing. EPA agrees 2280 with the commenter that “CR” is appropriate for the avian dietary toxicity and avian 2281*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 92 of 233 reproduction studies for all use patterns. This simplifies the test notes and with the 2282 appropriate triggers EPA would be able to require the needed testing. 2283 The following changes have been made to the aquatic areas column: 2284

 Avian dietary toxicity: change from “R” to “CR”; 2285

 Avian reproduction: change from “R” to “CR”. 2286 Test note 4 to the final Nontarget Organism Table in § 158.2240(c) triggers the 2287 avian dietary toxicity study based on the result s of the avian acute toxicity study. For 2288 the avian dietary study, testing in a sec ond species would be triggered based on the 2289 results of the avian dietary testing in the firs t species. Since the se cond test species will 2290 be required based on the results of the first species proposed test note 5 is no longer 2291 needed and is being removed. Test note 6 to the final Nontarget Organism Table in § 2292 158.2240(c) would trigger the avian reproducti ve study based on one or more of four 2293 specific criteria: There were no revisions to these criteria from t he proposed rule to the 2294 final rule. 2295 F. Water Quality Criterion 2296 1. Comment. A commenter argued that the r egistrants of any antimicrobial 2297 pesticide that has the potential to be discharged either directly or indirectly to surface 2298 water should be required to supply any additi onal data needed to derive a water quality 2299 criterion for the pesticide in question. 2300 2. EPA’s response

. As discussed in the conventionals ’ Response to Comments 2301 Document in docket EPA-HQ-OPP-2004-0387 (p. 104 ) at http://www.regulations.gov , ), 2302 the Agency’s pesticide registration process, including its data requi rement regulations, 2303 adequately considers the endpoints that ar e protected under the Clean Water Act 2304 (CWA) as administered by the Office of Water (OW). When acceptable data are 2305 available, OPP uses these data in its risk assessment process. 2306*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 93 of 233 The purpose of a water quality criterion under the CWA is to determine the level 2307 at which a water body may be at risk for env ironmental damage. The purpose of certain 2308 data requirements for pesticide registration is to allow the Agency to determine the 2309 ecological risk of using a pesticide. T hus, these program offices within EPA have 2310 similar goals. While EPA has developed guidelines for developing Water Quality 2311 Criteria (WQC), the Agency has also re cognized that WQC c an be developed with a 2312 more limited data set. 2313 Pesticide registration data are valuable in assessing water quality risks. As noted 2314 in EPA’s 2005 Response to Comments Do cument on the conventional pesticides, 2315 EPA’s OW and OPP together dev eloped aquatic life benchmar ks for 71 pesticides or 2316 pesticide degradation products for States to use to establish targets for safe levels of 2317 pesticides for aquatic plants and animals. The benchmarks are derived from data 2318 submitted to EPA for pesticide registration. As of April 18, 2011, there are 242 pesticide 2319 chemicals with aquatic benc hmarks on EPA’s website 2320 ( http://www.epa.gov/oppefed1/ecorisk _ders/aquatic_life_benchmark.htm ). 2321 G. Sediment Testing 2322 1. Comment. The commenter asserted that EPA did not consider the 2323 environmental fate of a compound (suc h as the tendency of a chemical to 2324 absorb/desorb) when considering the need for sediment testing. 2325 2. EPA’s response. EPA disagrees with this comment. Test notes 17 and 18 to 2326 the final Nontarget Organism Table in § 158.2240(c) trigger the sediment studies based 2327 on the results of the aerobic soil or aquatic metabolism st udies and knowledge of the 2328 physical/chemical properties which express the env ironmental fate of the antimicrobial 2329 pesticide chemical. The soil partition coefficient (K d ) is used as an expression of the 2330 binding capability of the chemical to sedim ents. The Agency’s just ification for using K d 2331*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 94 of 233 > 50 as a criterion for requiring sediment test ing is that this value would capture those 2332 chemicals with about 80 percent adsorption to sediments (rel ative to organic carbon). 2333 The octanol-water partition coefficient (K ow ) and the soil organic carbon-water 2334 partition coefficient (K oc ) also are used by EPA as part of its decision process. Both 2335 values are frequently more available than either the K d or half-life values. Test note 17, 2336 the trigger for requiring an ac ute sediment study, considers all four of these values. 2337 Next, as explained in test note 18, the ch ronic sediment study is triggered based 2338 on the results of the acute sediment study as well as a re-examination of the K ow, , K oc , 2339 and K d . 2340 XII. Discussion of Key Comments on Nontarget Plant Protection Data 2341 Requirements 2342
The following represent the significant comments on the need for and evaluation 2343 of nontarget plant protection studies as proposed by EPA. The changes from the 2344 proposed rule to final rule are also described. 2345 A. Triggers for Higher-Tiered Plant Studies 2346 1. Comment. One commenter asked EPA to explai n the criteria used to trigger 2347 higher-tiered plant studies based on t he results of the algal studies. 2348 2. EPA’s response . The criteria to trigger hi gher-tiered plant studies are 2349 specified in proposed test notes 2 and 5 to the proposed nontarget plant protection table 2350 in § 158.2250. A toxicity level (EC 50 <1 ppm) indicates that the antimicrobial pesticide 2351 would have serious adverse affect(s) on algae at low concentrations. This could have 2352 serious consequences to nontarget algae species. Therefore, at this toxicity level, 2353 additional higher-tiered testing is required to further characterize the potential adverse 2354*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 95 of 233 affects to aquatic plants. EPA is retaining the toxicity trigger of <1 ppm in test note 5 to 2355 the final nontarget plant prot ection table in § 158.2250. 2356 In evaluating proposed test note 2 to the propos ed nontarget plant protection 2357 table in § 158.2250, EPA has considered the commenter’s suggested table for 2358 nontarget plants. For the seedling emergence study, the commenter used “CR” for 2359 most use patterns and suggested that the seedling emergence study should only be 2360 required “when environmental exposure is likely to result under normal usage conditions 2361 as determined by appropriate assessment me thods.” Another co mment (see response 2362 to comment 140.27 in the Response to Comments Document in the docket at 2363 http://www.regulations.gov ) advocated for the use of a Ri sk Quotient (RQ) approach for 2364 assessing plants. 2365 Based on this evaluation, EPA believes using “CR” for the seedling emergence 2366 study when triggered by a level of concer n approach (RQ approach) would provide EPA 2367 with the required data when needed. Test note 2 to the final nontarget plant protection 2368 table in § 158.2250 now reads as: Data ar e required if the ri sk quotient from any 2369 aquatic plant growth Tier II study exceeds a level of concern for aquatic plants. 2370 However, test note 2 also triggers the aquatic plant growth (aquatic vascular 2371 plant) study, and is still the approp riate trigger for that study. Today With this final rule , 2372 EPA is adding a new test note 10 to the final Nontarget Plant Pr otection Table in § 2373 158.2250, which will read the same as t he original, proposed test note 2 to the 2374 proposed nontarget plant protec tion table in proposed § 158.2250. 2375 B. Alternative Format for Plant Protection Data Requirements Table 2376 1. Comment. In the comments submitted to EPA, the commenters suggested an 2377 alternate antimicrobial plant pr otection data requirements table. 2378*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 96 of 233 2. EPA’s response

. The table suggested by the commenter is not adequate to 2379 evaluate the hazards and risks to nontarget plants from antim icrobial pesticides. The 2380 suggested table did not include test gui deline numbers, changed and reduced the 2381 number of use patterns, and pr oposed that all ecotoxicity pl ant studies are either not 2382 required or only conditionally required. The commenter contends that there are no 2383 circumstances where ecological effects pl ant data are relevant for antimicrobial 2384 pesticides, and that indoor uses should not be subject to environmental exposure or 2385 nontarget plant species risk a ssessments. EPA disagrees wit h many aspects of these 2386 comments and the suggested ecot oxicity data requirements table for plant species. 2387 As previously discussed in the preamble to the proposed rule (73 FR 59406-7) 2388 and in Units III

. and V

. of this rule, EPA disagrees that exposure for nontarget plants 2389 should be presumed to be minima l or nonexistent for antimicr obials applied indoors, or 2390 that tests are not required if t he test organism is the target species for the pesticide (see 2391

testnotes ACC comment, identified in the docke t by document ID No. EPA-HQ-OPP2392 2008-0110-0088.7, p. 12, test notes 1 and 2 to the commenter’s suggested table). 2393 Moreover, there are many outdoo r uses of antimicrobials t hat are not addressed in the 2394 commenter’s suggested table. FIFRA mand ates that EPA conduct a risk assessment 2395 for any uses for which exposure may occur in the various environmental 2396 compartments/media. Those risks are a ssessed separately for the various taxa 2397 including plants, categories (e .g., freshwater, saltwater), and short-term (i.e., acute) and 2398 longer-term (i.e., chronic) exposures. Assessing these potential risks necessitates 2399 having an appropriate ecotoxicit y data base for plant exposure and toxicity. This can 2400 only be accomplished by requiring plant studi es for the initial assessment. A tiered 2401 approach cannot be driven solely by risk quotients derived from a Tier 1 study. The fact 2402 that an acute risk quotient for a plant specie s does not exceed a level of concern for 2403*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 97 of 233 acute risk does not imply that a chronic risk does not exist or that data are not needed 2404 to assess that risk. The tri gger for a chronic test is more likely driven by the frequency, 2405 duration, or magnitude of the chronic exposure and the env ironmental properties of the 2406 pesticide. For example, plants might be subj ected to repeated low-level exposure that 2407 is not acutely lethal but which may impac t reproductive success and plant growth. 2408 EPA disagrees that the test substance for plant studies (in the commenter’s 2409 table) should be identified si mply as the “residue of concer n (ROC).” In its proposed 2410 nontarget plant data requirements table, EPA specified the test material (TGAI, TEP) to 2411 be used for each study. The test substance determination is made after reviewing the 2412 required environmental fate and physical/ chemical properties data and any other 2413 available information (e.g., open literature, cl osely related chemicals) to determine the 2414 substance of concern for expos ure of non-target plants and or ganisms. For example, if 2415 an applicant can adequately demonstrat e that the TGAI dissipates so rapidly that there 2416 would be no acute or chronic exposure, TGAI testing may be waived, and instead 2417 degradate testing may be required. 2418 The commenter also omitt ed all guideline numbers from its suggested data table. 2419 At this time, all data requi rement tables in 40 CFR par t 158 have guideline numbers 2420 since this is a method of providing informati on to applicants. Applicants are not required 2421 to use these guidance documents guidelines , but are encouraged to use these test 2422 guidelines when developing data. Since t hese guidelines have been developed via a 2423 rigorous process, as discussed in t he preamble to the proposed rule [ 73 FR 59387], 2424 “they represent the recommended approach to developing high-quality data that should 2425 satisfy EPA’s data needs for risk assessment.” 2426 XIII. Discussion of Key Comments on Applicator and Post-Application Exposure 2427 Data Requirements 2428*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 98 of 233 The following represent the signi ficant comments received on the need for and 2429 evaluation of applicator and post-application exposure studies as proposed by EPA. 2430 Changes from the proposed rule to the final rule are also described. 2431 A. Consistency With OSHA and Other Standards 2432 1. Comment. A commenter asserted that EPA should be consistent with OSHA 2433 and other standards with regard to ex posure limits and handling practices, and 2434 incorporate the OSHA standards into risk assessment evaluations . The commenter 2435 also asked that when EPA believes that an OSHA or American Conference of 2436 Governmental and Industrial Hygienists (A CGIH) standard is not adequately protective 2437 for an antimicrobial, that the fi nding should be substantiated. 2438 2. EPA’s response. The OSHA workplace standar d is the permissible exposure 2439 limit (PEL). When developing a PEL, OSHA cons iders the toxicity of the chemical, often 2440 using data from the open literature as well as the feas ibility that exposures could be 2441 reduced to the PEL using process modifica tions, engineering controls and personal 2442 protective equipment (PPE) . Approximately 500 PELs have been established. 2443 The ACGIH establishes health–based Thres hold Limit Values (TLVs), which are 2444 non-governmental guidelines used by profes sional industrial hygienists in making 2445 decisions about safe levels of exposure to a chemical substance in the workplace. The 2446 TLVs were established for some chemical s as early as 1946 and they are updated on a 2447 regular basis as new health effects informa tion becomes available. Like the OSHA 2448 PELs, the TLVs are based on health effects data from the open liter ature. However, 2449 unlike the OSHA PELs, feasib i lity issues are not considered in establishing TLVs. TLVs 2450 are not available for most pesticide chemicals. 2451 However, for those pesticide chemical s with both TLVs and RfCs (Reference 2452 Concentrations are established by OPP based on studies submitted by the registrants), 2453*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 99 of 233 the RfCs are often lower than the TLVs. There could be several reasons for such 2454 differences. The data used by OPP is subm itted by the pesticide registrants and the 2455 toxicity database data base is composed of animal studies. So, uncertainty factors are 2456 used to derive the RfCs (exposure limits). Instead of animal studies, ACGIH prefers to 2457 rely on epidemiology studies/case reports of human, particularly worker, exposures from 2458 the literature and on pr ofessional judgment. 2459 For example, ACGIH and OPP establis hed different inhalation limits for 2460 formaldehyde based on slightly different interpre tations of the same literature studies. 2461 The TLV for formaldehyde is 300 ppb and the OPP “RfC” for occupational uses is 100 2462 ppb. Although the TLV is great er than the “RfC,” ACGIH does acknowledge in their TLV 2463 documentation that irritation can occur in some workers at levels of 100 to 300 ppb. 2464 EPA believes that an existing OSHA or AC GIH standard should be considered as 2465 part of EPA’s hazard evaluation. However, before using an OSHA or ACGIH standard, 2466 EPA would review the standard and the heal th effects (toxicology) documents 2467 supporting the standard’s develop ment to determine if EPA believes that the standard 2468 provides adequate protection. EPA agrees wit h the commenter that EPA’s evaluation of 2469 an existing OSHA or ACGIH standard s hould be part of its hazard evaluation 2470 documentation. 2471 In its proposed rule, EPA proposed in t he applicator exposure table (40 CFR 2472 158.2260(a)(1)) and the post-application ex posure table (40 CFR 158.2270(a)(1)) to 2473 use established workplace standards, such as OSHA’s. The proposed language was: 2474 If EPA determines that industrial st andards, such as the workplace 2475 standards set by the Occupational Safety and Health 2476 Administration, provide adequate protection for a particular 2477 pesticide or a particular use pattern, applicator exposure data may 2478 not be required for that pesticide or the use pattern. Applicants 2479 should consult with the Agency on appropriate testing before the 2480 initiation of studies. 2481*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 100 of 233 In addressing this comment, EPA realized that this proposed language is 2482 misplaced and also needs some text ual modification. As discussed above previously , 2483 an OSHA PEL or ACGIH standard is part of haz ard evaluation. If the PEL or TLV is 2484 determined to be adequate to fulfill EPA’s select ion of a toxicity endpoint, then the types 2485 and number of toxicity studies that may be required is impacted, not the need for 2486 exposure data. Therefore, EPA has removed the language originally proposed for § 2487 158.2260(a)(1) and § 158.2270(a)(1 ) concerning use of OSHA standards. With 2488 modifications, the following langu age appears in the final toxicity Table, rule in § 2489 158.2230(e): 2490 If EPA determines that industrial st andards, such as the workplace 2491 standards set by the Occupational Safety and Health 2492 Administration, provide adequate protection for a particular 2493 pesticide or a particular use pattern, additional toxicity data may 2494 not be required for that pesticide or the use pattern. 2495 B. Poisoning Incident Data 2496 1. Comment. “Poisoning incident data” should not be incorporated into this 2497 regulation unless the EPA can pr ovide criteria to trigger the need for exposure data 2498 based on poisoning incidents. Regulating ba sed upon anecdotal reports of “poisoning” 2499 is not appropriate. 2500 2. EPA’s response . Both proposed § 158.2260(b) and § 158.2270(b) contained 2501 the following trigger for requiring exposure data : “Scientifically s ound epidemiological or 2502 poisoning incident data indicate that adverse health effects may have resulted from 2503 handling of the pesticide." EPA understands that anecdotal reports may or may not 2504 indicate a cause-effect relationship, i.e., that adverse health e ffects may or may not 2505 have resulted from exposure to the pestici de. EPA agrees that anecdotal reports may 2506 not substantiate a clear dose response relati onship of “poisoning,” and therefore, when 2507 not substantiated, are not appropriate for regulatory endpoints. In-depth information on 2508*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 101 of 233 the dose response is the critical in formation needed for regulatory endpoints, and 2509 poisoning incident data rarely include this info rmation. However, EPA ’s intention was to 2510 use scientifically credible information as a tri gger for requiring exposure data. Based on 2511 this comment, EPA has revised the toxicity triggers in § 158.2260 and § 158.2270 to 2512 clarify that poisoning incident data must have a clear caus e effect relationship to 2513 indicate that adverse health effects may have resulted from exposure to the pesticide. 2514 C. Use of Existing Post-Application Exposure Data 2515 1. Comment. A commenter argued that there is a significant amount of post2516 application exposure data available that should be considered/used before requiring 2517 data under FIFRA. 2518 2. EP A’s response . EPA acknowledges that ther e are existing exposure data 2519 either in the literature, or via other governmental organizations such as OSHA, or 2520 academia, etc. When availabl e and appropriate, EPA uses such exposure data and/or 2521 information in its risk assessments. For exam ple, the risk assessments for both chlorine 2522 dioxide and ethylene oxide relied heavily on t he workplace air concentration monitoring 2523 data available in OSHA’s Chemical Exposur e Health Database (CEHD), formerly known 2524 as, Integrated Management In formation System (IMIS). To access CEHD, users 2525 navigate on the OSHA homepage ( http://osha.gov/) to Chemical Exposure Health Data 2526 under the Data and Statistics section towards the bottom right of t he page. Users can 2527 search CEHD by Establishment Name, State, Zip Code, Year Range, Standard 2528 Industrial Classification (SIC), North Amer ican Industrial Classification System Code 2529 (NAICS), Chemical Abstracts Service Nu mber (CAS), Chemical Name, or Result 2530 Range. 2531 Applicants who are aware of existing data that could fulfill a data requirement 2532 should submit the data to EPA. EPA will consider the appropriateness and robustness 2533*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 102 of 233 of the data, and, if appropriate, will use t he data in the Agency’s risk assessment. 2534 D. Soil Residue and Indoor Surf ace Residue Dissipation Studies 2535
1. Comment. A commenter claimed that there is little justification for requiring 2536 the soil residue dissipation and indoor surface residue dissipation studies. 2537
2. EPA’s response . In the proposed rule, EPA conditionally required the soil 2538 residue dissipation study for both occupatio nal and residential scenarios. EPA agrees 2539 that the likelihood of requiri ng soil residue dissipation data is low for the majority of 2540 antimicrobial use patterns. The low likelihood is reflected in the “CR” designation in the 2541 proposed post-application exposure data re quirements table for the soil residue 2542 dissipation study for both occupational and re sidential use patterns. No changes are 2543 needed. 2544 In the proposed rule, EPA required the i ndoor surface residue dissipation study 2545 for both occupational and residential scenarios. However, the likelihood of requiring 2546 indoor surface residue dissipation data is high for residential products such as 2547 antimicrobial-treated clothing and plastic c onsumer items/toys, as well as direct 2548 applications such as carpet shampoos, l aundry detergents, and fl oor cleaners that are 2549 antimicrobial products. Theref ore, the indoor surface resi due dissipation study for the 2550 residential use sites will remain “R” as proposed. 2551 However, EPA has re-evaluated the “R” pr oposed for occupational use sites. 2552 When compared to residential use sites, occupat ional use sites are less likely to result 2553 in the need for indoor surface residue dissipation data. Ther efore, the data requirement 2554 for indoor surface residue data has been revised from “R” to “CR” for o ccupational uses. 2555 In most manufacturing setti ngs, there is less contact wit h surfaces than in most 2556 residential scenarios. For ex ample, under most circumst ances workers do not crawl 2557 around the floors of manufacturing plants. The need for indoor surface residue 2558*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 103 of 233 dissipation data for workers is limited by the residue distribution where contact may 2559 occur. EPA now agrees that t he occupational use sites are less likely to result in the 2560 need for indoor surface residue dissipation da ta, and therefore, the “R” has been 2561 revised to “CR.” 2562 E. Non-Dietary Ingestion Study 2563 1. Comment . A commenter assert ed that the proposed requirement for non2564 dietary ingestion is impractical and unneces sary, and, in fact, could be replaced by 2565 modeling. 2566 2. EPA’s response. EPA agrees that the non-di etary ingestion study is 2567 impractical, as a stand-alone direct m easurement study. Non-dietary ingestion 2568 exposure (i.e., incidental oral ingestion by children) is of potential conc ern for treated 2569 articles or surfaces that may be accessed by children. For example, uses such as 2570 carpet shampoo, hardwood floor treatments, pressure-treated wood, and impregnated 2571 materials (including but not limited to plasti c toys or treated clothing) are assessed for 2572 non-dietary exposures when toxicity criteria are triggered. In all of these instances, non2573 dietary ingestion exposures are estimated using residue data from the treated surface 2574 combined with activity factors for children’ s behaviors (e.g., frequency of hand-to-mouth 2575 contact). Often, EPA models th is route and pathway of expos ure using inputs from the 2576 available , and reliable published research. If EPA were to require data to estimate this 2577 exposure pathway, EPA would require surface residue data, rather than requiring the 2578 actual monitoring of children or having individual registr ants collecting data on 2579 frequency of hand-to-mouth activities, as thes e are not chemical-specific. Given the 2580 unlikelihood of requiring non-dietary ingestion exposure studies, EPA has 2581

remove d determined to not finalize this proposed data requirement from and its 2582*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 104 of 233 accompanying test note 12 in the final Post-Application Exposure Table as well as the 2583 accompanying test note 12

. in § 158.2270(e). 2584 XIV. Discussion of Key Comments on Environmental Fate Data Requirements 2585 The following represent the signific ant comments received on the need for and 2586 evaluation of environmental fate studies as proposed by EPA. Changes from the 2587 proposed rule to the final rule are also described. 2588 A. Need for Environmental Fate Data for Indoor Uses 2589 1. Comment. Several commenters argued that the proposed environmental fate 2590 data requirements for indoor uses of antimicrobials should not exceed those in part 158 2591 for conventional pesticide chemicals, since ant imicrobials are not directly broadcast into 2592 the environment. 2593 2. EPA’s response . As explained in the proposed rule, there is now a greater 2594 concern regarding indoor uses of antimicr obials because those antimicrobial uses can 2595 lead to environmental exposure when they go down

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- drain. The rationale for 2596 requiring environmental fate data for antim icrobials mirrors that of Unit XI.A

. for 2597 requiring nontarget organism data for antimicrobials. 2598 There are many uses for which a high potential for exposure exists, and these 2599 uses may require a more extensive environment al fate data set that could also include 2600 aerobic and anaerobic metabolism studies. Howe ver, such uses will typically require a 2601 much reduced first tier data se t with additional testing tri ggered if the results of the 2602 required data indicate a potential risk that needs further characterization. 2603 B. Transformation Products 2604 1. Comment . A commenter argued that the A gency has not clearly stated when 2605 environmental fate data on the transformation pr oducts would be required. Additionally, 2606*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 105 of 233 the commenter also wanted to understand t he data that would be required if the 2607 substance degrades quickly? 2608 2. EPA’s response . For environmental fate dat a, the Agency evaluates 2609 transformation products on a case-by-case basis , using several sources of information. 2610 First, the transformation products need to be i dentified. While product chemistry data 2611 can provide some information on degradates , environmental fate data provide data 2612 specific to a particular environmental compar tment. Environmental fate studies provide 2613 information on the stability and persistence of the active ingredient and its degradation 2614 products in the various environmental media. For example, in the hydrolysis study, a 2615 half-life >30 days indicates that the substance is stable to hydrolytic processes, i.e., the 2616 substance did not degrade. Similar determi nations are made based on the results of 2617 the photodegradation in soil and water studies, and the aerobic and anaerobic 2618 metabolism in soil and water studies after revi ew of the required fate data. Monitoring 2619 and incident data, if available, also may i ndicate stability and persistence. There could 2620 also be environmental fate data conducted on a related chemical or information from the 2621 open literature. This analysis is critic al to determining not only the need for 2622 environmental fate data for transformation pr oducts, but also is the first step for 2623 determining the need for nontarget organism or nontarget plant data for transformation 2624 products. 2625 EPA proposed criteria to require testi ng of transformation/degradation products 2626 or leachate residues in proposed § 158.2280(a )(2) and (3). To respond to this 2627 comment, EPA also considered a simila r comment on transformation/degradation 2628 products or leachate residues for nontarget plant and organism testing (see Unit 2629 XI.B ). .). In response to these comments, EPA determined to clarify and revise the 2630 criteria for testing of transformation/degr adation products and leachate residues for 2631*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 106 of 233 nontarget plant and organisms, and environmental fate, (§ 158. 2250(b), 2632 158. 2240(a)(3 ), ) and § 158.2280(a)(2)) to read as follows: 2633 (2) Data on transformation/degradat ion products or leachate 2634 residues of the parent compound ar e also required to support 2635 registration, if the A gency determines that the 2636 transformation/degradation/leachate products meet one of the 2637 following criteria: 2638 (i) More toxic, persi stent, or bioaccumulative than the parent, 2639 (ii) Have been shown to cause adverse effects in mammalian or 2640 aquatic reproductive studies, or 2641 (iii) The moiety of concern (i.e., functional group in the parent 2642 chemical molecule that imparts adverse effects) remains intact. 2643 EPA also determined to clarify and revi se the criteria for testing of 2644 transformation/degradation pr oducts and leachate residues for nontarget plant (§ 2645 158.2250(b)) to read as follows: 2646 (b) Data on transformation/degradation pr oducts or leachate residues of the 2647 parent compound are also required to support registration, if the Agency 2648 determines that the transformation/degr adation/leachate produc ts meet one of 2649 the following criteria: 2650 (1) More toxic, persistent, or bioaccumulative than the parent, 2651 (2) Have been shown to cause adverse effects in mammalian or aquatic 2652 reproductive studies, or 2653 (3) The moiety of concern (i.e., f unctional group in the parent chemical 2654 molecule that imparts adverse effects) remains intact. 2655 EPA would use these criteria to dete rmine if environmental fate data on the 2656 transformation/degradation products or leachate residues are required. Therefore, if the 2657 environmental fate studies on the parent indi cate the transformation product(s) is, for 2658 example, more persistent in soils, then t he same environmental fate data required for 2659 the parent are required for the transformation product(s). If concerns are identified, then 2660 higher-tiered environmental fate and/or ecological effects data on the 2661 transformation/degradation produ ct(s) would be required. 2662 It should be noted that the criteria for determining whether to assess risks from a 2663 chemical substance and/or its degr adation products when conducting a down

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Page 107 of 233 analysis are different from those discussed above previously . Those criteria are 2665 discussed in response to comment 130.4 in the Response to Comments Document in 2666 the docket at http://www. regulations.gov

. 2667 C. Photodegradation in Soil Study 2668 1. Comment . A commenter claimed that EPA has not sufficiently explained why 2669 a photodegradation in soil study would be required if a s ubstance hydrolyzes and its 2670 behavior is known from its soil profile. 2671 2. EPA’s response . EPA proposed to require the photodegradation in soil study 2672 for only one use pattern: Wood preservatives. Wood products that have been treated 2673 with wood preservatives are often in contact wit h soil, and therefore it is possible for the 2674 wood preservative chemical, as well as its transformation and degradation products, to 2675 leach out from the treated wood product. To understand the fate of wood preservative 2676 chemicals in soil, first requires an understandi ng of the soils properties. Soil profiles are 2677 descriptions of soil properties, both physica l and chemical. Examples of physical 2678 characteristics would include: color, bulk dens ity, and texture. Examples of chemical 2679 characteristics would include: pH of the soil, organic matter content, and Cation 2680 Exchange Capacity (CEC). Depending on the so il profile, an antimicr obial pesticide can 2681 undergo chemical and/or biochemical (biodegradat ion) processes. For example, if the 2682 pH of the soil is less than 7, the antimicrobial can undergo hydrolysis and become 2683 nonpersistent, or if the pH of the soil is basic , the antimicrobial could remain stable and 2684 become persistent. If the or ganic carbon content of a soil is high, then the soil has a 2685 high microbial population which facilitate s the biodegradation process. Hence the 2686 nature of a soil (soil profile) is an important indicator of how a pesticide may behave in a 2687 soil. 2688*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 108 of 233 Many applicants are well aware of soil prof iles, since EPA asks for the soil profile 2689 to be submitted along with the results of the studies in soils. A number of soil profile 2690 databases data bases are available: Two of the databases data bases used by OPP are 2691 one from USDA and one called CLARION. 2692 In this final rule, EPA has retained the requirement for a phot odegradation in soil 2693 study for the wood pres ervatives use pattern. The photodegradation in soil study is 2694 required for all wood preservatives, except for two circumstances. First, if the 2695 antimicrobial is an inorganic substance or a metal salt, then a photodegradation study 2696 does not provide applicable information fo r inorganics and metal salts that do not 2697 degrade (chemically or bi ochemically). Second, if data from the standardized soil 2698 profiles show that the chemical is likely to readily degrade microbially or undergo redox 2699 reactions (degrade chemically ) , ) to such a degree that there is no formation of 2700 degradation/transformation/leachate produc ts of concern (as defined in § 2701 158.2280(a)(2)), then the photodegradation study in soils may study would not be 2702 required. needed. EPA is adding a new te st note 10 to replace proposed test note 10 to 2703 has revised the proposed environmental fate table in § 158.2280

. N ew test note 10 to 2704 the Environmental Fate Table, so that the test note 10 to the final Environmental Fate 2705 Table in § 158.2280(c) explains this condition the conditions for not requiring the 2706 photodegradation in soil study. 2707 D. Aquatic Sediment Study 2708 1. Comment. A commenter claimed that EPA is unclear about the triggers that 2709 would lead to the requirement for an aquatic sediment study, and how down

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- D ) modeling could affect the need for this study. 2711 2. EPA’s response

. Proposed Test notes 5 and 13 to the proposed 2712 environmental fate table in § 158.2280 trigger the aquatic sediment study for all use 2713*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 109 of 233 patterns except the aquatic areas use patte rn. EPA has re-evaluated the need for the 2714 aquatic sediment study and the appropriate triggers. EPA agrees that having two 2715 triggers, both of which use a weight-of-evi dence evaluation process, is confusing, and 2716 believes that one trigger (proposed test note 13) would be sufficient for triggering the 2717 aquatic sediment study. In t oday ’s action this final rule , EPA is removing test note 5 2718 from the test note column fo r the aquatic sediment study data requirement. Based on 2719 this re-evaluation, EPA also believes that the aquatic sediment study should be required 2720 for the antifoulant coatings and paints use pattern since an antifoulant use would meet 2721 the criteria of the tr igger in test note 13, which is: “...data are required based on the 2722 potential for aquatic exposure an d if the weight-of-evidence indicates that the active 2723 ingredient or principal trans formation products are likely to have the potential for 2724 persistence, mobility, nontarget aquatic toxicity, or bioaccumulation.” Antifoulants are 2725 released/applied directly to the aquatic environment. These products are often 2726 manufactured to be persistent, and because of the continuous release process, some of 2727 the active ingredient is likely to be transfe rred to the bottom of the water column and 2728 then be adsorbed to the sediment. This is likel y to result in adverse effects on nontarget 2729 benthic organisms. Since this meets the triggers for r equiring the study, today in this 2730 final rule EPA is changing the “CR” for the aquatic sediment study for the antifoulant 2731 coatings and paints us e pattern to “R.” 2732 The aquatic sediment study provides information about the 2733 degradation/dissipation proce sses under field conditions. The results of D

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- D down the 2734 drain modeling are unlikely to provide appropr iate information to determine the need for 2735 the aquatic sediment study. The current version of the D

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- D down the drain model 2736 estimates concentrations of chemical substa nces in the water column downstream of 2737 wastewater treatment faciliti es, but does not estimate conc entrations in the sediment. 2738*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 110 of 233 G. Monitoring of Represent ative U.S. Waters Study. 2739 1. Commen t. The commenter noted that ther e is no guidance on how to conduct 2740 a “monitoring of representative US U.S. waters” study, and that EPA has not provided 2741 the criteria for triggeri ng a “monitoring of represent ative U.S. waters” study. 2742 2. EPA’s response . The commenter is correct: EPA does not have a guideline 2743 for conducting this study. For all pesticides, such monitoring (studi es) of representative 2744 U.S. waters is a very rare occurrence. If EPA were to require such a monitoring study, 2745 protocols would have to be developed to s pecify a great deal of information: 2746

 At which locations would the monitoring occur, and how often would the 2747 monitoring occur? 2748

 Is the sampling for ground water, surf ace water, or the estuarine/marine 2749 environment? 2750

 Which chemical substances would be m onitored? Is just the antimicrobial 2751 (parent) to be analyzed, or would the transformation/degradation products also be 2752 analyzed? Such a protocol would be specific to a particular pes ticide, where that 2753 pesticide is used, and where the pesticide ha s been detected, and could not necessarily 2754 be used for a different pesticide. 2755 For the monitoring of representative U. S. waters data requi rement, the term 2756 “residue of concern” (ROC) is currently s pecified in the Environmental Fate Data 2757 Requirements Table in the test substance to support column. Since the ROC would be 2758 determined during protocol development, EPA is adding this information as part of a 2759 new test note 17 to the final Envir onmental Fate Table in § 158.2280. 2760 As stated in the preamble to the pr oposed rule, a WOE approach would be used 2761 to determine if a monitoring of repr esentative U.S. waters study should be required. 2762*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 111 of 233 The preamble to the proposed rule discusses th is aspect in more detail (73 FR 59413). 2763 EPA expects this study to be rarely required. 2764 H. AWPA and ASTM Methods 2765 1. Comment. A commenter arg ued that AWPA method E 11-97 or E20-04, and 2766 ASTM Method D5108-90 “are of limited or no relevance to estimating environmental 2767 exposures” for wood preservatives, or antif oulants, respectively. According to the 2768 commenter, the results of t he ASTM method are not suitable for “estimating release 2769 rates for regulation purposes.” The commenter believes that both methods 2770 “overestimate leach rates and are not in tended for use in risk assessments.” The 2771 commenter also provided information to i ndicate that ASTM Method D5108-90 has been 2772 replaced by ASTM D6442-06. 2773 2. EPA’s response

. Proposed Test note 15 to the pr oposed environmental fate 2774 table in § 158.2280 triggers the special leaching data requirement for the wood 2775 preservative use pattern. EPA’s intent in s pecifying that it would accept an ASTM or 2776 AWPA method was to allow applicants to use these readily available protocols. 2777 However, as noted in the proposed testnote test note , protocol review was still required 2778 for some of these methods. Since the co mmenters believe that these AWPA methods 2779 are inappropriate, but have not offered alternative methods , test note 15 to the final 2780 Environmental Fate Table in § 158.2280(c) is revised to remove the AWPA methods. 2781 Test note 12 to the final Environmental Fate Table in § 158.2280(c) is added to require 2782 protocol review. 2783 Test note 16 to the proposed environmental fate table in § 158.2280 triggers the 2784 special leaching data requirement for the ant ifoulant coatings and paints. Since the 2785 commenter indicated that the ASTM met hod has been replaced, EPA believes that 2786 specifying an ASTM method number in regulatory text may provide insu fficient clarity, at 2787*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 112 of 233 some point in the future. Therefore, test note 16 to the final Environmental Fate Table 2788 in § 158.2280 is revised to remove the AST M methods. Test note 12 to the final 2789 Environmental Fate Table in § 158.2280(c) is added to require protocol review. 2790 XV. Discussion of Key Comments on Down - the - Drain Analysis 2791 The following represent the significant comments received on the need for and 2792 performance of a down

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- drain analysis as proposed by EPA. Changes from the 2793 proposed rule to the final rule are also described. 2794 A. Changes to Down

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- Drain Analysis Based on Comments Received 2795 1. Comment . Some commenters expressed c oncern regarding EPA’s proposal 2796 to exclude antifoulants and wood preservatives from testing designed to protect POTWs 2797 and the aquatic environment. These comm enters contend that these compounds may 2798 reach POTWs through sources such as hu ll blast water, landfill leachate, and 2799 centralized waste treatment facilit ies. They think EPA should revisit this assumption to 2800 verify its accuracy. 2801 2. EPA’s response. Based on this comment, EPA did re-evaluate its original 2802 determination to exclude antifoulant coat ing and paints, wood preservatives, and 2803 aquatic areas from down

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- drain analysis. EPA still believes that it is appropriate to 2804 exclude aquatic areas from a down

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- drain analysis. As discussed in the preamble 2805 to the proposed rule (73 FR 59390) aquatic areas in clude lakes, ponds, streams, 2806 drainage ditches, and other bodies of water. T hese would not be expected to result in 2807 down

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- drain releases and are therefore un likely to be discharged to a WWTP. 2808 Based on its re-evaluation, EPA believes that a down

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- drain analysis is 2809 needed for the wood preservative, and antifoulant paints and coatings use patterns, as 2810 well as the all other use pa tterns category. There are a num ber of sources of indirect 2811 releases of antifoulants and wood preserva tives to surface water via WWTPs. The 2812*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 113 of 233 Emission Scenario Document (ESD) for Wood Pr eservatives, which is part of the OECD 2813 Series on Emission Scenario Document s, documents numerous sources of 2814 environmental releases directly to surface wa ter. The ESD also describes various types 2815 of wood preservative facilities where there may be environmental releases to the facility 2816 drain that subsequently drains to a WWTP. Some of the types of wood preservative 2817 facilities identified in the OECD ESD for w ood preservatives include automated spraying 2818 plants, dipping/immersion plants, and plant s that employ vacuum-pressure and double 2819 vacuum processes. According to this OE CD ESD for wood preservatives, it is also 2820 possible for releases to sewage treatment plants to occur from some treated wood 2821 products, such as noise barriers. 2822 According to the OECD Emission Scenario Document (ESD) for Antifouling 2823 Products, in addition to the numerous source s of direct environmental releases to 2824 surface water resulting from the use of ant ifoulant paints and coatings, there is the 2825 potential for antifoulants to ent er sewage treatment plants as a result of application and 2826 removal of antifoulant paints at boatyards and marinas. 2827 Thus, OPP’s Antimicrobial Division (AD) will perform a down

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- drain 2828 assessment for every product with an applicable use or exposure scenario that has the 2829 potential for waters containing antimicrobi als to reach a WWTP. To perform this 2830 assessment, the Agency is requiring data on the biodegradation of an antimicrobial 2831 pesticide and its potential toxicity to WWTP microorganisms in an activated sludge 2832 basin. For some antimicrobial pesticides, the Agency will also require the activated 2833 sludge sorption isotherm test to determine removal from wast ewater via partitioning to 2834 activated sludge. For additional informa tion on the changes m ade to the proposed 2835 environmental fate data requirements table see response to comment 134.1 in the 2836 Response to Comments Document in the docket at http://www.regulations.gov

. 2837*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 114 of 233 B. Use of E-FAST Model 2838 1. Comment . According to one commenter, EPA staff indicated at the part 158, 2839 subpart W Antimicrobials Data Requirements Workshop held on November 6, 2008 that 2840 the E-FAST model may have been based on m unicipal WWTPs that received only 2841 “residential” discharges. The commenter suggest ed that is very unlik ely and stated that 2842 according to the E-FAST manual, the m odel was based on data from actual U.S. 2843 municipal WWTPs. Nearly every municipal WWTP receives discharges from many 2844 types of non-residential sources, like commercial facilities, medical facilities, institutions, 2845 and cooling water systems (which are comm on in commercial buildings). Even in 2846 smaller communities, POTWs receive wast ewater from residential and commercial 2847 (e.g., schools, stores, restaur ants, hotels/motels, and/or medi cal facilities) sources. 2848 Most municipal WWTPs also receive bot h process and non-process discharges from 2849 industrial facilities. Some commenters conte nd that the E-FAST m odel is applicable as 2850 a screening-level model for all antimicrobi al use patterns with discharges that are 2851 typically rinsed down

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- drain including agricultural premises and equipment, food 2852 handling/storage establishment s, residential and public access premises, medical 2853 premises and equipment, industrial processes and water systems, swimming pools, and 2854 others. 2855 2. EPA’s response. The E-FAST documentation m anual indicates that the down 2856

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- drain module was develope d as a screening-level model for estimating 2857 concentrations of chemicals in surface wate r that may result fr om the disposal of 2858 consumer products into household wastewater . The model developers have confirmed, 2859 however, that the database data base of WWTPs that is accessed by this module 2860 consists of domestic WWTPs that receive wastewaters predominantly from residential, 2861 commercial, and institutional sources, and not solely from residential sources. In 2862*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 115 of 233 modeling releases of antimicrobial pestici des to environmental media, the appropriate 2863 data inputs, methods, and tool s are dependent upon the source of the environmental 2864 releases. To assess exposures and risks to re leases of antimicrobial pesticides to 2865 surface water from residential, commercia l, and institutional sources, the down

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- 2866 drain module of E-FAST is the most appropriate tool. 2867 To assess exposures and risks to antimicr obial pesticides from manufacturing, 2868 processing, and industrial use facilities, the general population and ecological 2869 exposures from the industrial re leases module of E-FAST is the most appropriate tool. 2870 The decision to use the general population and ecological ex posures from the industrial 2871 releases module is made on a case-by-case bas is considering the av ailability of data 2872 required as inputs to the module, and the potential for significant exposure. For 2873 example, a low volume use may not require use of this module. 2874 EPA agrees that the E-FAST model is applicable as a screening-level model for 2875 all antimicrobial use patterns with disc harges that are typically rinsed down

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- drain , 2876 including agricultural premises and equipm ent, food handling/stor age establishments, 2877 residential and public access premises, medi cal premises and equipment, industrial 2878 processes and water systems, swimming pools, and others. 2879 C. Exceedance Levels 2880 1. Comment . Some commenters questioned the justification fo r the following 2881 exceedance levels that were used by EPA to evaluate potential risks to aquatic 2882 organisms: 2883 i. Potential risks from e ffects to aquatic invertebrates and fish: Exceedance of 2884 the chronic concentration of concern (COC) fo r 20 or more days triggers a potential for 2885
concern; 2886*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 116 of 233 ii. Potential risks from effects to aquat ic invertebrates and fish: Exceedance of 2887 the acute COC for 4 or more days tr iggers a potential fo r concern; and 2888 iii. Potential risks from effects to algae: Exceedance of the COC for algae for 4 2889 days or less may trigger a concern and is evaluated on a case-by-case basis. 2890 2. EPA’s response

. These Exceedance levels and corresponding number of 2891 days of exceedance that trigger pot ential for concern are those cited on page 7

- 7 of 2892 EPA/OPPTS/OPPT’s “Revised Draft New Chemical s Decision Guidelines Manual” 2893 dated April 17, 2001. in EPA/OPPTS/OPPT's "Interpret ive Assistance for Sustainable 2894 Futures Summary Assessment", last updated August, 2011. The justification that the 2895 potential for chronic risk to aquatic organisms may exist if the predicted environmental 2896 concentration (PEC) exceeds the chronic COC and the exceedance occurs for 20 days 2897 or more per year is documented on page 11 of “Interpretive Assistance for Sustai nable 2898 Futures Summary Assessment , ” updated January 22, 2007 : 2899 “...although there is a "The potential for chronic risk to aquat ic organisms may 2900 exist ONLY if the PEC exce eds the chronic COC for 20 da ys or more per year. If 2901 exposure occurs for 20 days of more per year, the concentration of the chemical 2902 in the surface water to may reach levels exceeding the hazardous level, the levels 2903 are not exceeded for a sufficient duration of time to induce any associated with 2904 chronic effects

. (Lynch et al., 1994). The 20-day criterion is derived from partial 2905 life-cycle tests (Daphnid chronic and fish ear ly life-stage tests) that typically 2906 range from 21 to 28 29 days in duration. Low conce nt r atio n for chronic risk exists 2907 if the COC is ex ceeded on fewer than 20 days per year or the PEC is less than 2908 the chronic COC

. ” ." 2909 The justification for the potential for ac ute risks to aquatic organisms appears on 2910 page 12: 2911 "The potential for acute risk to aquatic organisms exists if the predicted 2912 environmental concentration (PEC) is gr eater than the acute concentration of 2913 concern (COC). 2914 If Acute COC > PEC: Low concern for risk 2915 If Acute COC < PEC: Potential for risk" 2916*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 117 of 233 EPA notes that risk is influenced by both the duration of exposure and the 2917 likelihood of that exposure occurring. Of ten mathematical models are used to estimate 2918 exposures and risks. There are two types of models: Deterministic or probabilistic. 2919 Probabilistic modeling is a tec hnique that utilizes the ent ire range of input data to 2920 develop a probability distribution of risk or ex posure rather than a single point value. 2921 The analysis identifies the probability that t he exposure exceeds the COC and for what 2922 timeframe. Deterministic modeling is based on select input data that result in a single 2923 point estimate. The estimate either ex ceeds or does not exceed the COC. Models 2924 such as E-FAST have the capability of prov iding either deterministic or probabilistic 2925 results. Consequently, criter ia for determining whether or not testing on aquatic 2926 organisms is required need to take into a ccount the possibility that the estimated 2927 exposure could be modeled using either det erministic or probabilistic modeling. 2928 Therefore, two test notes to the final Nontarget Or ganism Table in § 158.2250 have 2929 been revised to include a probabilistic trigger for down

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- drain analyses, while 2930 retaining the existing deterministic trigger for releases of antim icrobials that are 2931 expected to enter WWTPs. Test note 7 to the final Nontarget Organism Table in § 2932 158.2250(c) triggers the acute fr eshwater invertebrate toxici ty study (TEP testing) and 2933 the acute freshwater fish toxicity study (TEP testing). Test note 12 to the final Nontarget 2934 Organism Table in § 158.2250(c) tr iggers the fish life-cycle study. 2935 D. Evaluation of Discharges to Still Water and to Salt Water 2936 1. Comment . During the Antimicrobial Da ta Requirements Workshop held on 2937 November 6, 2008, EPA staff indi cated that evaluation of disc harges to still water and to 2938 salt water would be challenging. The co mmenter’s argued that the E-FAST model 2939 manual suggests that these discharges can be readily evaluated with appropriate input 2940 data and elimination of the PDM (Pr obabilistic Dilution Model) option. 2941*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 118 of 233 2. EPA’s response . EPA believes that the co mmenter misunderstood the 2942 context of the Information provided by EPA staff both in the propos ed rule and at the 2943 presentation on November 6, 2008. E-FAST has two m odules for estimating releases 2944 to surface water: The down

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- drain module, and the general population and 2945 ecological exposure from i ndustrial releases module. 2946 When the down

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- drain module of E-FAST is r un without the PDM option, the 2947 results are limited to estimates of concent rations in surface water downstream of 2948 domestic wastewater treatm ent facilities. The down

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- drain module has no option 2949 for estimating concentrations in non-flowing wate rbodies such as lakes, bays, estuaries, 2950 and oceans. The discussion at the November 6, 2008, Workshop focused solely on the 2951 down

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- drain module. 2952 E-FAST, however, has the capability for evaluating discharges to still water and 2953 to salt water from discharges to WWTPs th at receive manufacturing, processing, and 2954 industrial use releases, but not from discharges to surface water via domestic WWTPs. 2955 The general population and ecological exposure from industrial releases module is 2956 designed to estimate releases to air, wa ter, and land from manufacturing, processing, 2957 and industrial use of chemical substances. The database data base for estimating 2958 releases to WWTPs that primarily receive wastewater from manufacturing, processing, 2959 and industrial uses requires estimates of re leases to environmental media from models 2960 such as ChemSTEER (Chemical Screening Tool for Exposures and Environmental 2961 Releases), a model develope d by EPA’s OPPT or from data and calculations included 2962 in standard scenarios, also developed by OPPT 2963 ( www.epa.gov/oppt/exposure/pubs/chemsteerdl.htm ). The general population and 2964 ecological exposure from i ndustrial releases module includes an option for estimating 2965 concentrations in lakes, bays, estuaries, and oceans. 2966*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 119 of 233 E. Parameters for Down

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- Drain Analysis 2967 1. Comment . Several commenter’s argued that EPA’s approach for down

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- 2968 drain chemicals separates the exposure and the effects of the a ssessment and subjects 2969 chemicals to similar testing requirements re gardless of the mass of chemicals disposed 2970 of in the environment. According to these commenters, the fact that EPA does not 2971 guide testing by the extent of environmental exposure is wasteful for ingredients which 2972 will reach the environment at low levels. Even for chemicals which are used at greater 2973 volume, the commenters claime d that there is no proof t hat EPA’s program will achieve 2974 its goal without being wasteful and some co mmenters believe that EPA’s approach will 2975 likely result in significant unwarranted costs in animals, time, and dollars. The 2976 commenters asserted that this will result in unnecessary loss of animals, increased 2977 costs to the consumer and will negatively affect produc t innovation as new product 2978 development will be slowed due to the extra regulatory burden. The benefit to the 2979 environment of the EPA approach, according to the commenters, is likely to be small 2980 and not commensurate with its costs. 2981 2. EPA’s response . EPA disagrees with this comment. Three key input 2982 parameters for the down

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- drain model are: 2983 i. Percent removal of antimicrobial pesticide during wastewater treatment; 2984 ii. Concentrations of concern for ant imicrobial pesticides based on acute and 2985 chronic end-points for freshwat er fish, freshwater invertebr ates, and freshwater plants; 2986 and 2987 iii. Wastewater treatment plant influent volume of antimicrobial pesticide. 2988 As demonstrated in the sens itivity analysis of the down

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- drain model in the 2989 document, “Four Case Studies of Antimicr obial Pesticides in the Down-the-Drain 2990 Screening Model, Using the Proposed Approac h for a Screening-Level Environmental 2991*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 120 of 233 Fate Assessment” ( available identified in the docket at http://www.regulations.gov by 2992 document ID number EPA-HQ-OPP-2008-0110-0044 ), the amount of chemical 2993 disposed in the environment strongly influences the results of the down

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- drain 2994 model. It is possible that if the amount of chemical di sposed is small (i.e., WWTP 2995 influent volume is low and/or high percent removal during wast ewater treatment), that 2996 the predicted surface water concentration of t he antimicrobial, even for a chemical of 2997 high toxicity, would not exceed the Agen cy’s level of concern. Under such 2998 circumstances, higher-tier testing (environmental fate, ecotoxicity, and plant protection) 2999 is unlikely to be triggered. Since , higher-tier testing is triggered only if the down

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- 3000 drain model indicates that the predict ed concentration of the antimicrobial may 3001 adversely affect aquatic organisms this r educes the number of tests required, and 3002 therefore the animals, time, and dollars. 3003 EPA also notes that two of the three key input parameters needed to run the 3004 down

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- drain model, percent removal during wastewater treatm ent and wastewater 3005 treatment plant influent volume do not involv e animal testing and would not lead to loss 3006 of animals. Fate tests required to determi ne removal during wastew ater treatment via 3007 biodegradation and adsorption are inexpensiv e. No costs are associated with 3008 wastewater treatment plan WWTP influent volume. 3009 F. Acute and Chroni c Toxicity Endpoints 3010 1. Comment . At the Antimicrobial Data Requirements Workshop held on 3011 November 6, 2008, EPA staff indi cated that chronic aquatic toxicity endpoints might not 3012 be used to evaluate antimicrobial discharges from municipal WWTPs. A commenter 3013 argued that since EPA/OW requires municipal WWTP s to conduct both acute and 3014 chronic toxicity tests regularly as condi tions of CWA-regulated National Pollution 3015 Discharge Elimination System (NPDES) permits, both acute and chronic endpoints 3016*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 121 of 233 should be evaluated by EPA/OPP to ensure that antimicrobial discharges will not cause 3017 toxicity in municipal WWTP effluent. 3018 2. EPA’s response . To assess whether the proposed screening level 3019 assessment and tiered system of data requirements prov ides the data needed to 3020 assess exposure and risk of antimicrobial pesticides released to the environment via 3021 down

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- drain use patterns, the Agency conduc ted four case studies (73 FR 59408- 3022 9). Based on this comment, EPA has re-e valuated the approach used for the case 3023 studies, in which the higher-tiered data wa s triggered based on the results of the 3024 available data. To ensure that antimicrobial discharges will not cause toxicity to aquatic 3025 organisms downstream of WWTP effluents requires an eval uation of both acute and 3026 chronic toxicity endpoints. This means t hat the chronic ecotoxicity data needs to be 3027 submitted at the same time as the acute ec otoxicity data, so both types of studies are 3028 available for EPA to use for the ecological ri sk assessment. Also see Units XV.A and B. 3029 Consequently, in the final Nontarget Organism Table in § 158.2250(c), the table 3030 descriptors for the fish early-life stage and aquatic invertebrat e life cycle tests have 3031 been changed from “CR” to “R” for the wood preservatives use pattern and the all other 3032 use patterns category. Test note 10 to t he final Nontarget Organism Table in § 3033 158.2250(c) has been modified to remove the trigger since it is no longer needed. 3034 XVI. Discussion of Key Comments on Residue Chemistry Data Requirements 3035 The following represent the signific ant comments received on the need for and 3036 evaluation of residue chemistry studies as proposed by EPA. Changes from the 3037 proposed rule to the final rule are also described. 3038 A. Scope of the Residue Chemistry Data Requirements 3039 1. Comment. Several commenters found the scope of coverage of the residue 3040 data requirements in § 158.2290(b) to be vague and confusing. Further, the ACC 3041*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 122 of 233 Biocides Panel asserted that this secti on required data for uses for which a FFDCA 3042 section 408 tolerance is not required and over which, therefore, EPA allegedly has no 3043 jurisdiction. 3044 2. EPA’s response . EPA is clarifying § 158.2290(b) which pertains to the scope 3045 of the residue data requirem ents. That section can be read as limiting the residue 3046 chemistry data requirements to pesticide pr oducts requiring a tolerance or tolerance 3047 exemption. This apparent lim itation is inconsistent wit h both the preamble’s general 3048 description of the scope this subpart W and the preamble’s description of the scope of 3049 the residue data requirements se ction, and is internally inc onsistent with the terms of § 3050 158.2290(b). Various commentators noted the lack of clarity in this portion of the rule. 3051 The preamble’s general discussion of the scope of subpart W made clear that 3052 this subpart was not limited to “antimicrobi al pesticides” as defined by FIFRA section 3053 2(mm) – which excluded antimicrobial pestici de uses subject to either FFDCA section 3054 408 or section 409 – but e xtended to among other things, “[p]esticide products for 3055 antimicrobial use in/on food” (73 FR 59385). In no way, however, did this discussion 3056 suggest or imply that the s ubpart is limited to antimicrobi al uses requiring FFDCA 3057 section 408 tolerances or exemptions from tolerances. To the contrary, the preamble’s 3058 discussion of toxicity data requirements ex pressly notes that data are needed under 3059 subpart W to assess dietary risk whether or no t a section 408 tolerance is required. The 3060 preamble specifically states that, although certain antimicrobi al food uses are regulated 3061 under the FFDCA by FDA under section 409 and not section 408, EPA still needs data 3062 on these uses to assess dietary risk to fu lfill its statutory obli gations under FIFRA 3063 section 2(bb)(2), which establishes t he FFDCA section 408 safety standard as a 3064 component of the FIFRA standard for registration/cancella tion for FIFRA pesticide uses 3065 that result in residues on food (73 FR 59394) . Further, the preamble’s discussion of 3066*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 123 of 233 residue chemistry data require ments states that these data are needed for “direct and 3067 indirect food uses” including application to “food or water” both to assess risk and for 3068 tolerance-setting purposes (73 FR 59401: “In addition to dietary risk assessments, 3069 residue chemistry data are used to establish pesti cide tolerance . . . .” ). Finally, both the 3070 preamble’s discussion of residue data requirem ents and the relevant rule text mention 3071 antimicrobial uses that woul d be excluded by a limitation of the rule to antimicrobial 3072 uses requiring tolerances. For example, both the preamble and rule te xt refer to “fruit 3073 and vegetable rinses,” antimicrobials “incorpora ted into a material that may contact food 3074 or feed,” and “[a]quatic uses that have the potential to re sult in residues in potable 3075 water” and the fact that all of these uses may not need section 408 tolerances (73 FR 3076 59401 and 59444). 3077 Accordingly, EPA is revising § 158.2290(b) to make clear it is not limited to 3078 antimicrobial uses which need FFDCA se ction 408 tolerances. With some 3079 modifications, EPA is retaining in § 158. 2290(b) a non-exclusive list identifying 3080 examples of antimicrobial products covered by this section. This revision to § 3081 158.2290(b) makes clear that the residue data requirements apply to antimicrobial 3082 products that may result in residues in food or water whether or not a FFDCA section 3083 408 tolerance is needed. Section 158.2290( b) is revised by replacing the opening 3084 lines introductory text of subsection paragraph (b)(1) with the following: 3085 “Residue chemistry data are required for: 3086 “ (1) Antimicrobial end-use products with uses that may result in residues 3087 in or on food including, but not limited to:” 3088 The first item in the list of covered uses now reads “Products that require a 3089 tolerance, tolerance exemption, or food additive regulation or clearance.” The insertion 3090 of the reference to food additive regulations and clearances is consistent with the rule’s 3091*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 124 of 233 scope which is not limited to pesticide us es regulated under FFDCA section 408. 3092 Additionally, each of the s ubparagraphs listing examples of covered uses has been 3093 revised to refer to “products” rather than “uses” for consistency and clarity. Although the 3094 subparagraphs are overlapping (i.e., a produc t may fall in more than one paragraph), 3095 the revised subsection now clarifies the overall scope of this the section. These 3096 revisions make § 158.2290(b) consistent with the scope of the rule described in the 3097 preamble and the scope of the to xicology data requirements. 3098 Not only are these changes consistent wit h the scope of the rule as discussed in 3099 the preamble (i.e. data requirements are not limited to uses needing section 408 3100 tolerances) but the revised la nguage’s focus on whether use of a pesticide may result in 3101 residues in or on food follows directly fr om the intent of the residue chemistry 3102 requirements as discussed in the preamble. There, EPA explaine d that the proposed 3103 requirements will provide information “to bet ter estimate human dietary exposure to 3104 antimicrobial residues in or on food or feed,” “to determi ne the composition of the 3105 pesticide residue and how much of the residue is present in food or animal feed,” and to 3106 “measure how much of the residue of concern is present in food, feed, and water” (73 3107 FR 59401). Further, the revis ed language is consistent with the scope of FFDCA 3108 section 408 (applies to “pesticide chemic al residue[s] in or on food”) and FIFRA 3109 (requires consideration of “resi dues that result from the us e of a pesticide in or on 3110 food”). It also follows directly from the existing data requirements applying to 3111 antimicrobials in part 161. T hose regulations provide that “Residue Chemistry Data are 3112 used by the Agency to estimate the exposur e of the general population to pesticide 3113 residues in food and for setting and enforcing to lerances for pesticide residues in food 3114 or feed.” 40 CFR 161.202(c)(1); see also 40 CFR 161.202(c)(2) (“re sults of tests on the 3115 amount of residues remaining on or in the treated food or f eed are needed to support a 3116*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 125 of 233 finding as to the magnitude and identity of resi due which result in food or animal feed as 3117 a consequence of a proposed pest icide usage”); 40 CFR 161.240( b)( 14) (Residue data 3118 on indoor use of pesticide “if such a use coul d result in residues in food or feed”). 3119 Finally, the revised language also tracks EPA’ s requirements for residue chemistry data 3120 under the current data requireme nts for conventional pestici des in 40 CFR part 158, 3121 subpart O. In the preamble to the proposed rule, EPA explained that the residue data 3122 requirements for antimicrobials were adapted from the conventiona l data requirements 3123 in subpart O (73 FR 59401). For uses of conventional pesticides, other than uses in 3124 agriculture, part 158 states that “[residue ch emistry] [d]ata may be required . . . if 3125 residues may occur in food or feed as a resu lt of the use.” (4 0 CFR 158.1410(a)(2)). 3126 The regulation also makes clear that this r equirement applies whether or not a tolerance 3127 is needed under FFDCA section 408. The regulat ion specifies that “most products used 3128 in or near kitchens require residue dat a for risk assessment purposes even though 3129 tolerances may not be necessary in all cases.” (Id.) 3130 The commenters’ concern that the re sidue chemistry requirements exceeded 3131 EPA’s jurisdiction under the FFDCA is addressed above in Unit IV. 3132 B. Complete Transference of the Antimicrobial into Food 3133 1. Comment . The commenter believes that additional clarification is needed 3134 concerning EPA’s statement, “in the absence of data [the Agency will] evaluate the 3135 need for a tolerance or tolerance exemption by assuming complete transference of the 3136 chemical into food over the lif etime of the treated product.” 3137 2. EPA’s response . Complete transference refe rs to an assumption that the 3138 Agency would initially make regarding the mi gration of antimicrobial residues from an 3139 impregnated food contact material to the food c ontacting that material over the typical 3140 use life of the antimicrobial-impregnated materi al. The worst-case assumption is that 3141*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 126 of 233 100 percent of the antimicrobial residues resu lting from use at t he maximum registered 3142 rate transfers into the food, which is t hen used to estimate a conservative dietary 3143 exposure. If the aggregate risk ca lculated using this conservative assumption, from use 3144 of the antimicrobial in question, is less t han EPA’s level of concern, then no measured 3145 data are needed. If the aggregate risk meets or exceeds EPA’s level of concern, then 3146 chemical-specific data quantifying residue migr ation to refine this dietary exposure 3147 component may be required. To refine t he exposure, the applicant may choose to 3148 perform one or more of the FDA protocols to estimate migration rate into food simulants 3149 (FDA/CFS AN, 2007, Preparation of P remarket S ubmissions for F ood C ontact 3150 S ubstances: C hemistry R ecommendations (Ref. 11 to the proposed rule, in the docket 3151 at http://www.regulations.gov ) )

. stimulants (see document ID number EPA-HQ-OPP3152 2008-0110-0013). Alternatively, or subsequently, the applicant may choose to conduct 3153 a chemical-specific nature of the residue on surfaces study and a migration study 3154 investigating actual impregnated materi als using representative foods. 3155 C. Alternative Formats for Residue Chemistry Data Requirements Table Suggested by 3156 Commenters 3157 1. Comment. Two different commenters sugges ted two different options as 3158 alternative approaches to the antimicrobial residue chemis try data requirement table 3159 proposed by EPA. One of the commenter s separated the residue chemistry data 3160 requirements into two tables, referred to as Part 1 and 2 [ ( ACC comment , identified in 3161 the docket at http://www.regulations.gov ; by document ID number EPA-HQ-OPP-2008- 3162 0110-0088.10 , p. 7 ]

. ). The other commenter s uggested a single table format [ ( CSPA 3163 Comment , identified in the docket at http://www.regulations.gov ; by document ID number 3164 EPA-HQ-OPP-2008-0110-0086.2 ]

. ). 3165*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 127 of 233 2. EPA’s response . All three of the commente r-suggested tables had the same 3166 five “Supporting Information” studies as the first section of the table proposed by EPA, 3167 but with various mixtures of “R,” “CR,” and “NR.” In the final rule , EPA has retained the 3168

same Supporting Information of the first section of the Residue Chemistry Table as 3169 proposed. However, EPA has adopted the commenters’ suggestion for a tiered format 3170 in the last two sections of the Residue Chemistry Table . After review, EPA believes the 3171 commenters’ suggested tiered approach is more suitable to antimicrobials than that 3172 proposed by EPA. All three commenter of the commenters’ tables suggested that Tier 1 3173 consist of a “Screening-level dietary ex posure assessment.” Although an applicant may 3174 opt to conduct a dietary exposure assessment, EPA does not consider this to be a data 3175 requirement. Applicants often conduct a dietary exposure assessment to understand 3176 the dietary risks before submitting an applicat ion to EPA. If submitted, EPA would 3177 review the assumptions used by the applicant and compare them to EPA’s modeling. If 3178 the applicant’s modeling indicates that diet ary risk is likely to meet or exceed the 3179 Agency’s level(s) of concern, the applicant may decide to continue on to Tier 2 or 3. 3180 Therefore, EPA has not added a requireme nt to conduct a dietary exposure 3181 assessment. 3182 Both the Part 1 Table and the single tabl e suggested that Tier 2 consist of a 3183 “Refined dietary exposure asse ssment.” As is the case for the commenter’s suggested 3184 Tier 1 “Screening-level dietary exposure asse ssment,” this is optional for the applicant; 3185 therefore, EPA has not added a requirement to conduct a refined dietary exposure 3186 assessment. 3187 Both the Part 1 Table and the single table suggested that Tier 3 consist of nature 3188 of residue on surface, bioaccumulation, magnitude of residue, residue analytical 3189 method, and storage stability. Thes e are each addressed individually below as follows : 3190*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 128 of 233 i. Nature of residue on surface. The Agency agrees that th is study is applicable 3191 and a valuable addition to the data set nece ssary to support registration and risk 3192 assessment of antimicrobial uses on/ in food-contact surfaces and impregnated 3193 materials (treated articles). EPA has added this study into to the final Residue 3194 Chemistry Data Requirements Ta ble in part 158, subpart W. 3195 ii. Bioaccumulation. EPA believes that the comment ers intended that this study 3196 apply only to fish and that the bioaccumula tion study required for ecological effects 3197 should substitute for the nature of the re sidue on surface study for aquatic uses or 3198 indoor/outdoor raw agricultural commodity uses. EPA has found that the fish 3199 bioaccumulation study is often not useful for residue chemistry purposes because 3200 characterization of fish residues is only required if the bioconcentration (of total 3201 residues) factor is > 1000 1,000 . The fish bioaccumulation study has not been adopted 3202 by EPA for residue chemistry. Of much more use to residue chemistry and retained in 3203 this final rule, are the fish metabolism and magnitude of the residue studies in fish 3204 described in OPPTS Guideline 860.1400. 3205 iii. Magnitude of residue (MOR). Commenters proposed this study by the very 3206 general title “Magnitude of residue.” EPA cons iders MOR to be any study designed to 3207 quantify “how much” of the residues of concer n will result in food, on surfaces, in water, 3208 etc., following use of an antimicrobial accord ing to label directions. The commenters 3209 stated in a footnote to this st udy that, in the case of food -contact sanitizers and treated 3210 articles, MOR would consist of a migration study. Because food-contact sanitizer and 3211 treated article uses comprise at least 80 per cent of all antimicr obial food uses, EPA has 3212 retained the migration study and the food-handling study by name but has moved them 3213 to a different tier. All the remaining pr oposed types of MOR studies are much more 3214 rarely required due to characteristics such as the use pattern and/or physicochemical 3215*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 129 of 233 properties of the antimicrobial in question. For that reason, the following have been 3216 grouped as “Higher tiered” studies in the final rule: Nature of the residue in plants, 3217 nature of the residue in livestock, residue anal ytical methods for tolerance enforcement, 3218 multiresidue method testing, potable water, fish, irrigated crops, m eat/milk/poultry/eggs, 3219 crop field trials, processed food or feed, and anticipated residues. 3220 iv. Residue analytical method. EPA agrees with the commenters that an 3221 analytical method for data collection is r equired whenever magnitude of the residue 3222 studies are required. The Agency has retai ned this study in the final Residue Chemistry 3223 Table. 3224

v. Storage stability. EPA agrees with the commenter s that storage stability data 3225 are required whenever magnitude of the residue studies are required. The Agency has 3226 retained this study in the fi nal Residue Chemistry Table. 3227 The Part 2 Table did not recommend requiring a Refined Dietary Exposure 3228 Assessment. Rather, its Tier 2 consists of studies entitled natur e of the residue in 3229 commodity, nature of the residue in liv estock, residue analytical methods for 3230 enforcement of tolerances, mu ltiresidue analytical method, magnitude of the residue: in 3231 commodities, in water, and in meat/milk/ poultry/eggs, storage stab ility, and anticipated 3232 residues. EPA agrees that all of these studies should be required and has retained all 3233 of them in the highest tier in the final Resi due Chemistry Table. Note that two of the 3234 commenter-suggested studies (nature of t he residue in commodity and magnitude of 3235 the residue in commodities) we re considered applicable only to RACs treated via a fruit 3236 and vegetable rinse; whereas, the analogous EPA data requirements apply to both crop 3237 plants and metabolically-active RACs. The dat a requirements in EPA’s final rule easily 3238 subsume the studies suggested by a commenter in Part 2. The commenters feel that 3239 EPA only has authority to require residue data for RACs of plants treated by a fruit or 3240*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 130 of 233 vegetable rinse whereas EPA interprets FIFRA and FFDCA, as amended by FQPA, to 3241 mean that data may be required for any use if necessary to support registration of any 3242 use under FIFRA (see Units XVI.A

. and IV ). .). 3243 As evidenced by the recommendation to divide EPA’s single proposed data 3244 requirement table into two tables (Parts 1 and 2), the commenter s believe the data 3245 requirements are distinctly different depending on the use pattern of interest. While this 3246 is sometimes the case, the Agency has found that there is much overlap between which 3247 studies are necessary to characterize the dietary exposure potentia lly resulting from a 3248 given use. This is why the test notes pr ovide the conditions under which each study is 3249 required, likely to be required, or not required. EPA has historically and currently used a 3250 single data requirement table for each scient ific discipline; doing so permits the 3251 interrelationships between use pattern, tier ing, and data needs to be fully evident. 3252 The commenters did not account for dat a needed to estimate dietary exposure 3253 associated with uses that do not require a FFDCA section 408 tolerance or exemption 3254 (see Unit XVI.A

. and Unit IV ). .). The commenters also did not account for data needed 3255 to estimate dietary exposure from food resi dues inadvertently resu lting from, but not 3256 limited to, discharges of antimicrobial-treat ed water from indoor industries, leaching 3257 from preserved lumber, or tr eatment of food crops when a public health claim is made 3258 on the label. 3259 XVII. Discussion of Key Comments on SAR and QSAR, and the OPPTS (now 3260 OCSPP) Integrated Testing Vision 3261 A. Guidance on Policies, Procedures, and Processes 3262 1. Comment . A commenter asked EPA to shoul d provide clear guidance on its 3263 policies, procedures, and processes on the use of alternative technologies such as SAR 3264 and QSAR, and the WOE approach. In addition, the commenter stated that EPA should 3265*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 131 of 233 also provide education and tr aining on these approaches. 3266 2. EPA’s response . The Agency encourages applicants to create submissions 3267 that include predictive techniques such as SAR and QSAR to fulf ill data requirements. 3268 As described in the white paper to the proposed ru le, entitled, “Use of Structure-Activity 3269 Relationship (SAR) Information and Quantitat ive SAR (QSAR) Modeling For Fulfilling 3270 Data Requirements for Antimicrobial Pest icide Chemicals and Informing EPA’s Risk 3271 Management Process” ( see document 45 in the docket at http://www.regulations.gov ID 3272 number EPA-HQ-OPP-2008-0110-0045 ) , an important part of the applicant’s 3273 submission is the rationale. The rational e, or WOE evaluation, is the part of the 3274 submission that explains the applicant’s belief as to why and how the predictive data 3275 would fulfill the data requirem ent. The WOE approach requires a critical analysis of the 3276 entire body of available data for consistency and biological plausibility. In support of a 3277 request that predictive data be considered, t he applicant would need to explain why it 3278 believes the surrogate data or the modeling are appropriate for the intended use and 3279 are of sufficient completeness and qualit y, and therefore would fulfill the data 3280 requirement. The Agency would evaluate ea ch submission with a WOE rationale on a 3281 case-by-case basis. 3282 The general types of information that are considered appropriate for a WOE 3283 approach would include: 3284

• Sufficiency of data . Studies that completely c haracterize both the effects and 3285 exposure of the agent have mo re credibility and support than st udies that contain data 3286
gaps. 3287

• Quality of the data . Potentially relevant st udies are judged for quality and 3288 studies of high quality are given more weight than those of lower quality. 3289*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 132 of 233 • Evidence of causality . The degree of correlati on between the presence of an 3290 agent and some adverse effect is an important consideration. 3291 Regarding SAR/QSAR, the white paper to the proposed rule (p. 30) discusses 3292 the five criteria set by the OECD for eval uating a model. EPA encour ages submitters to 3293 follow the established criteria set by OECD, and show how the model is validated for 3294 that particular pesticide chemical structure as a measure of the m odel’s applicability. 3295 Different computer software programs ar e used to estimate/predict different 3296 hazards (see: http://www.epa.gov/oppt/sf/tools/methods.htm ). This means that 3297 predictive software models for different scientific disciplines are not at the same level of 3298 development. The Agency has long standing experience in predicting (modeling) 3299 physical-chemical properti es, environmental fate, ecotoxicity, and experience in 3300 predicting carcinogenesis for certain classes of chemicals. However, the Agency is still 3301 gaining experience to become familiar with pr edictive approaches that look at other 3302 human health endpoints (e.g., reproductive, developmental), which have not been 3303 widely used at EPA. Given the different stages of predictive software development, 3304 EPA would expect to undertake a case-by-case evaluation of submitted WOEs. EPA 3305 encourages the use of integrat ed approaches that combine t he knowledge from existing 3306 databases data bases about the chemical of intere st with data from appropriate 3307 surrogate chemicals. 3308 EPA agrees that guidance on the policies, procedures, and processes for using 3309 alternative approaches such as SAR/QSAR is needed. EPA is In developing such a 3310 guidance document for pesticides and is seeking , EPA sought to harmonize its 3311 approach with that of C anada’s Pest Management R egulatory Authority. It is 3312 anticipated that The guidance document would be was issued as a North American Free 3313 Trade Agreement guidance document by the end of 2011

. in 2012. This guidance 3314*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 133 of 233 document will adhere adheres to the five OECD principles that were discussed in the 3315 white paper . Once finalized, this document will and is now considered to be the 3316 definitive source of information for app licants seeking to use SAR and QSAR 3317 approaches for fulfilling data require ments for pesticide registration. For information, 3318 see http://www.epa.gov/oppf ead1/international/naftatw g/guidance/guidance.htm. 3319 B. Integrating SAR/QSAR Within the Data Requirements Rule 3320 1. Comments . One commenter argued that there should be an explicit 3321 statement that SAR an d QSAR can be considered to fulf ill data requirem ents. Another 3322 commenter had concerns on codifying the use of SAR in 40 CFR part 158, Subpart A 3323 since that would mean that “SAR/QSAR Techniques would be applicable to 3324 conventional, biochemical and microbial, and antimicrobials pesticide chemicals.” 3325 Another commenter requested that SAR/QSAR be fully in tegrated within the rule. 3326 2. EPA’s response . EPA has and will continue to consider accepting 3327 SAR/QSAR to fulfill its data requirements on a case-by-case basis. Acceptance would 3328 be based on the information provided and most especially on the supporting rationale 3329 submitted to EPA. The Agency would evaluate the information submitted to determine if 3330 the applicant has provided information that is of sufficient quality and completeness. 3331 The Agency notes that validation of QSAR models is necessary before the predictions 3332 from those models can be fully integrated into the testing r equirements. To that end, 3333 QSAR models must be inclusive of pesticide to xicology data and chemical structures. 3334 Until these models become cust omized with pesticide informati on, full incorporation of 3335 predictive tools likely will be lim ited to a case-by-case basis. 3336 EPA agrees that if use of SAR/QSAR were to be codified in subpart A, that it 3337 would be applicable to all pesticide chemicals. At this time, EPA is not codifying the use 3338 of SAR and QSAR in subpart A. 3339*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 134 of 233 XVIII. Discussion o f Key Comments on Guidelines 3340 A. Commenters’ Concerns with Guidelines 3341 1. Comment: Several commenters i ndicated their belief that the current 3342 Harmonized Guidelines have signif icant problems, which include: 3343

 Lack of guidelines could create an unevenness from one company to another 3344 in how the data requi rements are applied. 3345

 Data requirements for which gu idelines are not available. 3346

 Older, outdated guidelines that need revision. 3347

 Draft guidelines that need to be finalized. 3348

 Older exposure guidelines that do not include information about the Human 3349 Studies Review Board. 3350

 Guidelines that were adopted with out the opportunity for public comment. 3351 According to the commenters, lack of current guidelines could create an unevenness 3352 from one company to another in how t he data requirements are applied. The 3353 commenter argued that the Agency needs to provide current, consistent, and reliable 3354 guidance and standards for each data r equirement. The commenters recommended 3355 that EPA should finalize all of its gui delines before the final rule is published per the 3356 recommendation from OMB. 3357 2. EPA’s response . EPA’s Harmonized Test Guidelines are publicly-available at 3358 http://www.epa.gov/ocspp/pubs/frs/home/guidelin.htm. The Harmonized Guidelines 3359 contain recommendations on how to conduct a st udy that is most likely to provide the 3360 information needed by EPA for making a registration decision. . 3361 The Harmonized Guidelines are guidance. The guidelines themselves do not 3362 impose mandatory requirements. Applicants are not r equired to submit studies 3363 developed according to the guidelines to fulfill a data requirement. However, EPA 3364*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 135 of 233 encourages applicants to use the guidelines. These guidelines were developed to 3365 provide applicants, who would be conducting the studies, with recognized approaches 3366 for developing high quality data, guidance on evaluating and reporting data, definition of 3367 terms, and suggested study protocols. It would not be possible to address every 3368 conceivable circumstance that could occur when conducting a particu lar study. Instead 3369 the guidelines provide a fr amework that provides recommended approaches for 3370 conducting studies while offering flexib ility and accommodation for individual 3371 circumstances where appropriate. EPA has re viewed and accepted many studies, on a 3372 case-by-case basis, that were not conducted in accordance with current guidelines, but 3373 which provided suitable informati on for risk assessment purposes. 3374 Since guidelines cannot account for every conceivable ci rcumstance, EPA, for 3375 certain studies, proposed a “required” or “h ighly suggested” protocol submission and 3376 review step in the test notes to the tables in the proposed rule. Generally, these pertain 3377 to those studies that are “newer” or have not been routinely conduct ed. Given that the 3378 applicant community and contracting laborat ories would have less experience in 3379 conducting these kinds of “new er” studies, protocol submi ssion, review, and meetings 3380 about proposed protocols are beneficial to bot h the applicant and EPA, and help assure 3381 that the study submitted for review should provide the information needed by EPA for its 3382 registration decision. 3383 EPA acknowledges that in some instances there are: Data requirements for 3384 which guidelines are not av ailable; outdated guidelines that need revision; and draft 3385 guidelines that need to be fina lized. Ideally, up-to-date final guidelines would be 3386 available for every data requirement. Up-to- date guidelines increase the possibility that 3387 EPA will receive useful data and that applican ts can produce such data in the most 3388 cost-efficient and consistent manner. Howeve r, given the rapidly evolving scientific 3389*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 136 of 233 methods for conducting toxicity, exposure, and ecological studies with pesticides, study 3390 guidelines often need frequent updating to incl ude the latest techniques and methods. 3391 Moreover, the need for openness and transparen cy means that devel oping a guideline 3392 or updating an existing one can be a lengthy process. In a recent letter to CropLife 3393 America (June 26, 2009), (Ref. 11 12 ) the Agency discussed the timeframe for 3394 developing the Terrestrial Field Dissipat ion Guideline (835.6100), which spanned 15 3395 years. During that time period, there we re presentations to the SAP, at various 3396 symposia including ones conducted by t he American Chemical Society and the 3397 American Society of Agronomy, and to a wo rkshop in Washington, DC co-hosted by 3398 EPA and Canada’s Pest Management Regulatory Agency. 3399 Thus, the reality is that test guidelines will always be a work in progress. At the 3400 same time, EPA is implementing a regulator y program under FIFRA and FFDCA section 3401 408 under which it must make timely decisio ns on the safety of pesticide products 3402 based on toxicity and exposure testing. Guidance on optimal testing procedures 3403 remains an Agency goal but the absence of te sting guidelines is not a barrier to the 3404 imposition of testing requirements necessary to make the required statutory findings. 3405 In 2008, OMB, during its Executive Order 12866 review of the proposed rule, 3406 recommended that certain draft guidelines be finalized before publishing the 3407 Antimicrobial Data Requirements fi nal rule. These guidelines were: 3408

 Applicator product use information (OPPTS 875.1700) 3409

 Post application product use information (OPPTS 875.2700). 3410

 Indoor surface residue dissipation (OPPTS 875.2300). 3411

 Non-dietary inges tion (OPPTS 875.3000). 3412 In the proposed rule ( 73 FR 59382, October 8, 2008 ; 73 FR 59382 ), EPA 3413 discussed that the publicly-ava ilable versions of these draft guidelines were only 3414*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 137 of 233 available on the SAP portion of EPA’s website (73 F R 59399

– 59401). 3415 http://www.epa.gov/scipoly/sap/meet ings/1998/march/contents.htm . Since the two 3416 product use information related guidelines (875.1700 and 875.2700) are expected to 3417 provide similar guidance for the narrative descr iptions that the related data requirements 3418 call for, EPA intends to finalize these guidelines update them together. 3419 The indoor surface residue dissipation draft guideline (875. 2300) will be updated 3420 before issued in the near future. final form to account for new advances in how 3421 exposure is measured and modeled and to provide more information on additional 3422 methods. EPA intends to revise the dr aft guideline to expand the methods for 3423 antimicrobial uses, and has begun to work with EPA’s Office of Research and 3424 Development (ORD) to develop additional methods (e.g., one current project is to 3425 develop guidance for testing in small scale air chambers). EPA is also consulting with 3426 the Consumer Product Safety Commission (CPSC ) to review their sampling methods for 3427 similar products (e.g., chemicals leaching from fabrics). 3428 Also, as previously discussed, the proposed data requirement referencing the 3429 non-dietary ingestion guideline was removed from (identified as 875.3000) is not 3430 included in the final Post-Applicator Ex posure Table in § 158.2270. As a result, that 3431 draft guideline is no longer referenced in Part 158. (See Unit XIII.D ). .). 3432 In addition, as noted in the proposed rule , EPA notes that it has reviewed and 3433 accepted many studies, on a case-by-case basis, that were not conducted in 3434 accordance with current final guidelines, but which serve its needs and provide suitable 3435 information for risk assessment purposes. The guidelines themselves do not impose 3436 mandatory requirements. In stead, they present recogni zed standards for conducting 3437 acceptable tests, guidance on evaluating and reporting data, definition of terms, and 3438 suggested study protocols. The draft guidelines , therefore, serve as a starting point for 3439*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 138 of 233 developing study protocols. The Agency’s scientists can also provide guidance to 3440 applicants, registrants or task forces on aspects of study des ign that is often discussed 3441 at pre-protocol submission meetings. The A gency’s scientists are always willing to work 3442 with individual applicants or registrant s to develop study designs to fulfill data 3443 requirements. 3444 EPA acknowledges that the guidelines for dermal and inhalation exposure 3445 studies need revisions to account for new advances in how exposure is measured and 3446 modeled. To provide needed information to the public and applicants, EPA will change 3447 the way these guidelines are referenced on the Harmonized Guidelines website by 3448 adding links to the SAP and Human Studies Re view Board (HSRB) meetings at which 3449 the changes needed to conduct one of these studies were publicly discussed. 3450 Since the publication of the proposed ru le on October 8, 2008, EPA has worked 3451 to update and finalize a number of guidelines. On April 15, 2009, EPA published In the 3452 Federal Register of April 15, 2009 (74 FR 17479) (FRL 8352-8) , EPA issued a Notice 3453 of Availability describing updates to 16 environmental fate guidelines. On 3454 In the Federal Register of January 27, 2010 , (75 FR 4380) (FRL 8437-2), EPA 3455 published four draft product perfo rmance guidelines for comment . These four 3456 guidelines ( (i.e., 810.2000, 810.2100, 810.2200, and 810.2300 ) ). These four guidelines 3457 were developed over an extended period of time with multiple levels of review across 3458 divisions and program offices in EPA, ex pert external peer review by the FIFRA 3459 Scientific Advisory Panel , (SAP), and discussions with and comments from the 3460 regulated community. After soliciting public co mment in 2010, EPA announced the 3461 availability of the fi nal guidelines in the Federal Register of March 16, 2012 (77 FR 3462 15750) (FRL 9332–4). Many of the technical c hanges described in these four draft 3463 guidelines have been in use by t he Agency for several years. Three additional product 3464*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 139 of 233 performance guidelines (810. 2400, 810.2500, and 810.2600) should be published for 3465 comment in a timeframe similar to that of publication of the final rule for Antimicrobial 3466 Data Requirements. Similarl y, the nontarget organi sm and plant protection guidelines 3467 are expected to be finalized by the end of 2011

. 3468 Three additional Product Performance Gu idelines (i.e., 810.2400, 810.2500, and 3469 810.2600) published for public co mment on September 15, 2011 (76 FR 57031) (FRL 3470 8879–1), and in the Federal Register of June 27, 2012 (77 FR 38280) (FRL 9349–5), 3471 EPA announced the availability of the final guidelines. 3472 Also in the Federal Register of June 27, 2012 (77 FR 38282) (FRL 9333-1), 3473 EPA announced the availability of 26 Ecological Effects Test Guidelines in Series 850, 3474 and Groups B, C, D and F. In finalizi ng the guidelines, EPA changed the numbering 3475 and/or titles of certain guidelines, and split or merged other guidelines. EPA continues 3476 to work to revise the remaining Ecologic al Effects Test Guidelines, Group A, and 3477 anticipates finalizing many of these guidelines in 2013. 3478 Before finalizing a guideline, EPA provides many opportunities for public 3479 comment. EPA’s commitment to transparen cy is not new. Transparency allows all 3480 stakeholders to know what, how, and wh y EPA is adopting a guideline. EPA’s 3481 procedures for developing a guideline is descri bed in a Notice of Availability that 3482 published on August 28, 1996 (61 FR 44308 ) (FRL 5390-7 ): 3483

 Guidelines under development (whether new or being substantially revised) 3484 are made available for public comment. 3485

 Guidelines under development (whether new or being substantially revised) 3486 undergo an external peer review process. Most commonly, the peer review process 3487 would be a review by the FIFRA SAP. 3488*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 140 of 233  Reformatted guidelines (no substantial revisions) are not subject to review 3489 and comment. 3490

 Public review and comment is also used when EPA guidelines are being 3491 harmonized with OECD guidelines. 3492 B. Harmonization of Guidelines with OECD 3493 1. Comment. EPA should harmonize its gui delines with those of OECD. 3494 2. EPA’s response . EPA agrees with this comment and is continuing to 3495 harmonize guidelines, to the extent practicabl e, as they are revised. As noted on its 3496 website http://www.epa.gov/pesticides/science/guidelines.htm, EPA has several 3497 harmonization activities underway with the OECD. The Master List of Harmonized Test 3498 Guidelines includes a reference to an OECD guideline, once harmonized. All 3499 harmonized OECD test guidelines ( http://www.epa.gov/epahome/exitepa.htm ) fall under 3500 the OECD Mutual Acceptance of Data decision, which calls for acceptance for 3501 regulatory use by all OECD member nations . Additionally, under 40 CFR 158.70(d)(2), 3502 acceptance of testing conducted in accor dance with OECD protocols is described. 3503 Harmonized test guidelines reduce the burden on chemical producers and 3504 conserve scientific resources, including t he minimal use of laboratory test animals. 3505 They also form a basis for work shar ing and cooperation among all OECD countries. 3506 U.S. experts are engaged in harmonizati on activities through OECD to revise 3507 toxicology and ecotoxicology te st guidelines. These revisi ons will emphasize reduction, 3508 refinement, or replacement of animal testing, while incorporating the latest advances in 3509 science. Animal welfare concerns and in ternational regulator y needs are being 3510 considered in the course of these revisions of the test guidelines. In addition, EPA is 3511 actively engaged in OECD’s development and harmonization efforts for guidelines to 3512*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 141 of 233 address environmental fate, endocrine disrupto r screening, and efficacy of antimicrobial 3513 pesticides. 3514 Tests conducted in accordance with t he requirements and recommendations of 3515 the applicable OECD protocols can be used to develop data necessary to fulfill the data 3516 requirements. However, some of the OE CD recommended test standards, such as test 3517 duration and selection of test species, are less restrictive than those recommended by 3518 EPA. When using OECD protocols, applicants should be careful to observe the test 3519 standards so that the data generated will satisfy the EPA data requirements. 3520 C. Guidelines Specific to Antimicrobials 3521 1. Comment . The commenter claimed that guide lines specific to antimicrobials 3522 are needed. 3523 2. EPA’s response . EPA agrees that for certain sci entific disciplines or certain 3524 studies that antimicrobial -specific guidance may be needed. The data required to 3525 demonstrate product performance would be very different for an insect repellent or a 3526 termiticide versus that needed for sanitizers and disinfectants. Ex posure studies could 3527 be conducted differently for an antimicrobial used in a food-processing plant versus a 3528 conventional pesticide sprayed on an agricultural field. Exposure studies could also be 3529 conducted via the same method: A spray c an with an insecticide is assessed using the 3530 same techniques as a spray can with a di sinfectant with any differences in the 3531 assessment being attributed to actual use c onditions, such as, indoors versus outdoors 3532 or surfaces sprayed. For ot her scientific disciplines such as toxicology or product 3533 chemistry, generally, with a few exceptions, the guidance would be the same: A 3534 carcinogenicity, developmental, or reproducti ve toxicity study would be conducted 3535 similarly for an antimicrobial or a conventio nal pesticide. However, as noted in Unit 3536*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 142 of 233 X.F , ., the Ames assay may not be useful fo r assessment of mut agenic potential of 3537 antimicrobial pesticides. 3538 XIX. Discussion of Key Comments on Endangered Species Assessments 3539 A. Endangered Species Assessment for Antimicrobials 3540 1. Comment. The commenter argued that EPA needs to recognize the manner 3541 in which antimicrobials may result in envir onmental exposure and the regulations under 3542 statutes other than FIFRA in order to prom ote an effective and efficient approach to 3543 regulating antimicrobial pes ticides with regard to endangered and threatened species. 3544 According to the commenter, antimicrobials are not applied directly to the environment, 3545 but environmental exposures fr om antimicrobial pesticides result from point-source 3546 discharges or slow release from pe sticide-containing materials. 3547 2. EPA’s response . EPA agrees that there are differences between 3548 antimicrobial pesticides and agricultural pesticides. As discussed in the proposed rule 3549 (October 8, 2008 ; , 73 FR 59425), for agricultural pesticides, there is generally greater 3550 specificity relative to where a pestici de may be used compared to antimicrobial 3551 pesticides. Agricultural pesticides are typica lly used on crops. As part of its endangered 3552 and threatened species assessment, EPA extracts information on county-level crop 3553 occurrence and acreage within counties of par ticular crops from the most recent U.S. 3554 Department of Agriculture’s USDA National Agricultural Stat istics Services’ Census of 3555 Agriculture. Because antimicrobial pesticides are typically not applied directly to the 3556 environment, it is easier to delineate and overlay agricultural pesticide use with 3557 endangered or threatened species loca tions than to delineate and overlay antimicrobial 3558 pesticides use. Nevertheless, wood preserva tives, antifoulant paints and coatings, and 3559 other antimicrobial uses, including uses in s wimming pool water, industrial slimicides 3560 used in recirculating water cooling towe rs, and paper mills, have the potential for 3561*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 143 of 233 environmental exposures. The Agency is working to refine its endangered species 3562 assessment for antimicrobial pesticides to account for the unique mechanisms involved 3563 in application and use of antimicrobial pesti cides, and the different routes through which 3564 antimicrobial pesticides enter the environment. 3565 EPA recognizes that antimicrobials, like any other pesticide product, may be 3566 subject to other Federal, State and local laws . FIFRA requires tha t, before a pesticide 3567 may be lawfully sold or distributed in the United States, the product must be registered 3568 by EPA, unless the product is exempt from registration require ments. Prior to 3569 registering a pesticide product, EPA must firs t ensure that the pesticide, when used 3570 according to label directions, can be used without posing unreasonable risks to humans 3571 and the environment. The registration of a pesticide product, whether it is an 3572 antimicrobial or other type of pesticide product, is considered an “action” subject to the 3573 Endangered Species Act (ESA). The ESA requi res all Federal agencies to ensure that 3574 any action they permit or authorize will not result in likely jeopardy to the continued 3575 existence of endangered or threatened species, or destroy or adversely modify habitat 3576 designated as critical by the U.S. Fish and Wildlife Service (FWS) or National Marine 3577 Fisheries Service (NMFS). 3578 In order to ensure EPA’s actions are consistent wit h the ESA, the Agency must 3579 assess the potential for both direct and indi rect effects to any potentially exposed 3580 threatened or endangered species and critical habitat, independent of whether exposure 3581 results from a point-source discharge or t he slow release of a pesticide containing 3582 material. If effects may occur, EPA consul ts with the FWS or NMFS to determine 3583 whether there may be jeopardy to the specie s or destruction or adverse modification to 3584 habitat designated as critical. 3585 B. Method for Conducting Endangered Species Assessments 3586*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 144 of 233 1. Comment. A commenter claimed that E PA/OPP does not have a mature 3587 program currently in place for antimicrobi al environmental risk assessment generally. 3588 More specifically, the commenter contended that EPA does not have a program in place 3589 for assessing potential impacts on endangered and threatened species relevant to 3590 antimicrobials and their uses. The comm enter argued that until EPA scientifically 3591 substantiates data requirements to use in estimating antimicrobial environmental 3592 exposures and modeling and the potential for risks from such exposures, it will not be 3593 feasible to make any meaningful dete rminations on potential impacts to endangered 3594 species. The commenter concluded that it is thus premature for the EPA to determine 3595 how it should approach antimicrobial s with regard to endangered species. 3596 2. EPA’s response . EPA disagrees with the commenter. EPA has a robust 3597 program for completing antimicrobial environ mental risk assessments, as outlined in the 3598 preamble to the proposed rule (73 FR 59405). Environmental fate studies evaluate the 3599 mobility, distribution and dissi pation of a pesticide in various compartments of the 3600 environment, such as water, soil, air, and sedi ment. Ecological effects data are used by 3601 the Agency to determine the toxicological haza rds of pesticides to various nontarget 3602 organisms, such as birds, mammals, fish, bees, terrestrial and aquatic invertebrates, 3603 and plants. The required environ mental fate studies and ecol ogical effects (both plant 3604 and animal) data provide the foundation fo r an environmental risk assessment. EPA’s 3605 environmental risk assessment for antimicrobi als combines environmental fate studies 3606 with ecological effects data to determine the potential of the pesticide to cause harmful 3607 effects to nontarget organism s and plants. The data requi rements that will be codified 3608 in the final rule will provide sufficient in formation for EPA to perform an ecological risk 3609 assessment. 3610*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 145 of 233 EPA/OPP’s process for assessing the potential risks of a pesticide to federally 3611 listed threatened or endangered species and t heir designated critical habitat is 3612 described in the document titled “Overview of the Ecological Ri sk Assessment Process 3613 in the Office of Pesticide Programs, U.S. Environmental Protection Agency – 3614 Endangered and Threatened Species Effects Determinations” released in January 3615 2004. (Ref. 13). Appendix A to that document – “O verview of OPP’s Screening-Level 3616 Ecological Risk Assessment Process for Anti microbial Pesticides” – explains both the 3617 data needed and the process that would be us ed by EPA to assess potential risks to 3618 endangered and threatened species from antimicrobial pesticides. 3619 EPA’s assessment of potential impacts on endanger ed and threatened species 3620 begins with a screening level assessment to det ermine if there is a potential concern. 3621 When the screening-level ecological risk asse ssment raises potential concerns related 3622 to a listed species, EPA then conducts a s pecies-specific evaluation to refine the 3623 assessment. The more refined assessment s hould involve clear delineation of the 3624 action area associated with the proposed use of the pesticide and best available 3625 information on the temporal and spatial co-locat ion of the listed species with respect to 3626 the action area. EPA notes that with the publication of the proposed rule, the discussion 3627 in Appendix A is out of date. In re sponse to comments received on the proposed 3628 antimicrobial data requirement s, EPA indicated it is no l onger relying on its proposed 3629 approach classifying use patterns as high/low or minimal/significant exposure uses with 3630 regard to ecological effects testing. However, the Agency’s basic approach to 3631 endangered species risk assessments, which co mbine environmental fate studies with 3632 ecological effects data to determine the potential of the pesticide to cause harmful 3633 effects to endangered species, has not changed. In addition, the Agency will conduct 3634 an assessment for antimicr obial pesticides with down

- the

- drain uses, as described in 3635*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 146 of 233 response to comment 134.1 in the Response to Comments Document in the docket at 3636 http://www.regulations.go v

. . The codified data requirements and the down

- the

- drain 3637 assessment will extend AD’s ability to underst and the potential impacts of antimicrobial 3638 pesticides on endangered species. 3639 EPA cannot wait to comply with the ESA until newer, more advanced, models are 3640 available or additional data needs are determi ned: Federal agencies must comply with 3641 the ESA by performing their assessments and analyses using the best scientific and 3642 commercial data available. As a part of Registration Review, EPA is conducting 3643 species-specific environmental risk asse ssments that will allo w EPA to determine 3644 whether the antimicrobial pesticide product has “no effect” or “ma y affect” federally3645 listed threatened or endangered species (listed s pecies) or their designated critical 3646 habitats. When an assessment concludes that a pesticide product’s use “may effect” a 3647 listed species or its designated critical habitat, the Agency will consult with the FWS 3648 and/or NMFS, as appropriate. 3649 XX. Discussion of Key Comments on Endocrine Disruption 3650 A. 1. Comment

. The commenters noted that EPA di d not include any studies to 3651 assess endocrine disruption effects. 3652 B. 2. EPA’s response

. The commenter is correct that EPA did not include within 3653 the proposed subpart W, studies whose sole purpose is to assess endocrine disruption 3654 effects in avian and aquatic species. The Agen cy is also not including such studies in 3655 this final rule. 3656 With regards to toxicology data require ments, as required by FIFRA and FFDCA, 3657 EPA reviews a toxicological database data base of numerous studies to assess potential 3658 adverse outcomes from exposure to chemic als. Collectively, these studies include 3659 acute, subchronic and chronic toxicity, including assessments of carcinogenicity, 3660*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 147 of 233 neurotoxicity, developmental, reproductive, and general or systemic toxicity. These 3661 studies include endpoints which may be susc eptible to endocrine influence, including 3662 effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual 3663 maturation, fertility, pregnancy ra tes, reproductive loss, and sex ratios in offspring. EPA 3664 reviews these data and selects the most sensitive endpoints for relevant risk 3665 assessment scenarios from t he existing toxicological database data base

. 3666 With regards to ecotoxicity data require ments, as required by FIFRA and FFDCA, 3667 EPA reviews a nontarget organism database data base of numerous studies to assess 3668 potential adverse outcomes from exposure to chemicals. For ecological hazard 3669 assessments, EPA evaluates acute tests and chronic studies that assess growth, 3670 developmental and reproductive effects in different taxonomic groups. EPA reviews 3671 these data and selects the most sensitiv e endpoints for relevant risk assessment 3672 scenarios from the existing nont arget organism database. 3673 Through a separate effort, the Agency has also developed a screening battery to 3674 identify chemicals that may have effe cts on the hormone syst ems of humans and 3675 wildlife. As required under FFDCA section 408(p), the Agency developed the Endocrine 3676 Disruptor Screening Program (EDSP) to determine whether certain substances 3677 (including pesticide active and other ingredients) may have an effect in humans or 3678 wildlife similar to an effect produced by a “ naturally occurring estrogen, or other such 3679 endocrine effects as the Administrator may des ignate.” The EDSP employs a two-tiered 3680 approach to making the statutoril y required determinations. Tier 1 consists of a battery 3681 of 11 screening assays to identify the potential of a chemical substance to interact with 3682 the estrogen, androgen, or thyroi d (E, A, or T) hormonal syst ems. Chemicals that go 3683 through Tier 1 screening and are found to have the potential to interact with E, A, or T 3684 hormonal systems will proceed to the next stage of the EDSP where EPA will determine 3685*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 148 of 233 which, if any, of the Tier 2 tests are nec essary based on the available data. Tier 2 3686 testing is designed to identify any adverse endocrine-related effects caused by the 3687 substance, and establish a dose-response re lationship between the dose and the E, A, 3688 or T effect. 3689 Between October 2009 and February 2010, EPA issued test orders/data call-ins 3690 for 58 pesticide active ingredients and nine 9 inert ingredients. This list of chemicals 3691 was selected based on the potential for human exposure through pathways such as 3692 food and water, residential activity, and certain post-application agricu ltural scenarios. 3693 This list should not be construed as a list of known or likely endocrine disruptors. 3694 Under FFDCA section 408( p) the Agency must screen all pesticide chemicals, 3695 including antimicrobials. Accordingly, EPA anticipates issuing future EDSP test 3696 orders/data call-ins for all pesti cide active ingredients. 3697 For further information on the EDSP incl uding the status and test guidelines, 3698 please visit the website: http://www.epa.gov/endo/. 3699 XXI. Discussion of Key Comments on Effective Date of Final Antimicrobial Data 3700 Requirements 3701 A 1 . Comment

. Several commenters have express ed concern over when the final 3702 rule would take effect. One commenter stat ed that compliance with the Administrative 3703 Procedures Act requires EPA to apply any final rulemaking on data requirements for 3704 antimicrobials only to applications submitt ed after the effective date; otherwise, EPA 3705 would be promulgating the final rule retroactively. The commenter also asserted that 3706 EPA should be consistent in its implementat ion of effective dates, noting that EPA did 3707 not impose new data requirements on pending c onventional pesticide registrants when 3708 the conventional pesticide rules were revi sed. A second commenter suggested that 3709 registrations pending at the ti me of the final rule public ation be given conditional 3710*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 149 of 233 registration under section 3( c)(7) of FIFRA or under section 3(c)(5) if the requirements 3711 of part 161 have been met, and t hat implementation of t he part 158, subpart W data 3712 requirements occur at the ti me of periodic registration review. Another commenter 3713 noted that EPA has provided reasonable notice to registrants and recommends that 3714 EPA implement the rule as soon as techni cally feasible. A different commenter 3715 questioned whether additional Pesticide Registration Improv ement Act (PRIA) 3716 registration fees would be required for pending appl ications if the registrant did not meet 3717 new data requirements and withdrew the app lication, or if the Agency issued a 3718 determination that it c annot grant the application. 3719 B. 2. EPA’s response

. EPA will follow an approach similar to that used for 3720 conventional pesticides following the promulgat ion of that portion of 40 CFR part 158. 3721 As previously discussed, the final rule for antimicrobials contains 11 “new” data 3722 requirements. “New” means that the data requirement has never been required, or has 3723 rarely been required on a case-by-case bas is and has not been routinely considered 3724 during the Agency’s evaluation of the data needed for the purpose of risk assessment. 3725 The new data requirements being codified in clude eight that were proposed and three 3726 that have been added based on pub lic comments received about the proposed rule. 3727 EPA recognizes that during early implem entation of 40 CFR part 158, subpart W 3728 not all application packages may have all of the newly-required data. Therefore during 3729 early implementation of 40 CFR part 158, s ubpart W, EPA will accept for review and 3730 evaluation application packages that may not have all of the newly required data in 3731 appropriate cases supported by adequate justification. This early implementation period 3732 could extend up to two 2 years post-promulgation for sit uations in which a more time3733 intensive new study is missing but could be le ss for other situations, such as for less 3734 time-intensive new studies. The applicant shoul d address the issue of timing (i.e., why 3735*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 150 of 233 the data are not yet submitted and when the dat a can be submitted) with respect to any 3736 missing newly-required data, in their justification. 3737 EPA is statutorily required to evaluat e the proposed pesticide thoroughly to 3738 ensure that it will not unreasonably harm human health or the environment. For 3739 pesticides needing FFDCA section 408 tolerances, EPA is statutorily required to make a 3740 safety finding that the pesticide can be used with "reasonable certaint y of no harm." In 3741 cases where the application may not have all the required data, EPA would evaluate 3742 whether a registration determination or a safety finding can be made based on the 3743 available data or on the results of other studies in the pesticide’s database data base . If 3744 there is insufficient information, and if the database data base does not provide 3745 information on the endpoints that would be test ed, or data provided by the applicant or 3746 information in the database data base shows evidence of effects, EPA may not be able 3747 to make a registration decision or safety fi nding. In such cases, the application may be 3748 denied or the applicant may choose to withdr aw the application pending completion of 3749 the needed data. In some cases, conditi onal registrations may be appropriate for 3750 consideration. Among other things, a dete rmination that the pr oposed use will not 3751 significantly increase the risk of unreasonab le adverse effects on the environment will 3752 need to be made. If EPA can make that determination and the other elements for a 3753 conditional registration are met, then a conditional regist ration may be appropriate and 3754 the new data required as a condition of registra tion. If there is a basis for granting a 3755 conditional registration, t hen the timeframe for conditioni ng the registration would be 3756 determined based on factors such as the re quired studies involved and the length of 3757 time required to conduct those studies. 3758 Importantly, it should be noted that acc eptance of an application for processing 3759 during early implementation of 40 CFR part 158, subpart W , that does not result in a 3760*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 151 of 233 conditional registration , does not permanently relieve t he applicant from providing the 3761 newly required data. Based on the particular case involved, the Agency will employ 3762 appropriate mechanisms, for ex ample, through a DCI or th rough the registration review 3763 process, to ensure the generation and submi ssion of any missing newly-required data. 3764 With respect to pending applications that are withdrawn, additional PRIA 3765 registration fees will generally only be requi red if the applicant seeks to pursue the 3766 action again by submitting a new applicati on (and addressing the deficiencies in the 3767 original application). In withdrawal sit uations, the Agency provides a refund for any 3768 work that the Agency did not perform on the application followi ng a withdrawal. 3769 Similarly, a determination that the app lication cannot be granted does not require 3770 additional PRIA registration fees . In that case, additional f ees will only be incurred if the 3771 application is subsequently wit hdrawn or denied, and the app licant seeks to pursue the 3772 action again and submits a new application. 3773 XXII. Discussion of Key Comments on the Economic Analysis 3774 A. Comparing Estimates of Cost of the Proposed Rule 3775 1. Comment. A commenter performed an indepen dent economic analysis (EA) 3776 for the proposed rule. According to the comm enter’s analysis, the cost of proposed part 3777 158, subpart W is greater than that estimate d by the EPA. In addition, the unit test 3778 costs and frequency of tests used in the comm enter’s analysis are different than EPA’s. 3779 2. EPA’s response . EPA reviewed the commenter’s analysis and based on that 3780 review revised the EA for the final rule . EPA’s evaluation of the commenter’s EA 3781 indicated there were the followi ng differences between the two EAs: 3782

 The cost estimates used for the studies , 3783

 Overhead costs were included by the commenter, but not by EPA , 3784

 Costs for Registration Review (see Unit XXII.C .) .). 3785*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 152 of 233 The differences between the co st of the proposed rule as estimated by the commenter 3786 and the cost as assessed by the Agency fo r new registrations are explained in the 3787 following subunits. 3788 i. How data requirement costs are calculated. The annual cost of a data 3789 requirement is the product of th ree factors: Unit test cos t, probability of the test being 3790 required, and the number of regi strations in the industry per year for the registration 3791 type and use. That is: “ Industry Cost of a data requirem ent = Unit test cost x test 3792 probability x number of registrations .” These costs are summed for all data 3793 requirements, uses, and registration types to get the total annua l cost of the data 3794 requirements for the industry. 3795 ii. Differences in unit test costs. EPA acknowledges that there are significant 3796 differences between the Agency’s analysis and the commenter’s analysis regarding the 3797 unit test costs. According to the commenter’s EA, the cost s were provided to them by 3798 their client’s technical consultants, and are “based on quotes from laboratories, actual 3799 experience, and professional judgment.” The commenter did not provide sufficient 3800 information with which to evaluate the commenter ’s test cost estima tes. Additionally, 3801 EPA notes that having all test cost estimate s ending in zero could be indicative of 3802 estimation. 3803 EPA’s unit test costs for each data requi rement were obtained by contacting 3804 established contract resear ch organizations (CROs) to assess what the labs would 3805 charge to conduct studies according to specific designs provided by EPA, or as 3806 specified in OPPTS guidelines

. (now OCSPP guidelines). Upper and lower cost 3807 estimates were requested. For each test , the upper cost estimates from each CRO 3808 were averaged to obtain a high average estima te. A similar calculation was done for 3809*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 153 of 233 the lower cost estimate. EPA’s estimate is the average of the high and low average 3810 estimates. 3811 iii. Test costs and overhead costs. The commenter added 30 percent to their 3812 test cost estimates to a ccount for the overhead of t he registrants managing and 3813 overseeing the tests they contract to the labs. EPA acknowledges that there are costs 3814 other than test costs associ ated with registering and mainta ining the registrations of 3815 pesticide products. Overhead is a not new cos t, attributable to the rule, and EPA does 3816 not believe that overhead costs will change significantly as a result of codifying data 3817 requirements for antimicrobials. EPA does not include overhead costs in its economic 3818 analyses of data requirements rules because t he Agency accounts for other registration 3819 costs such as overhead in the Information Collection Request (ICR) for FIFRA Section 3 3820 Registration under the Paperwork Reduction Act. 3821 iv. Test probabilities. EPA’s test probabilities (the probabilities of tests being 3822 required for a registration actions) were bas ed on a sample of 70 actual antimicrobial 3823 registration actions out of 90 relevant new registration actions during the six 6 year 3824 period beginning 2000 and ending 2005, supplemented with EPA’s scientific judgment. 3825 The time period (2000-2005) was chosen for EPA’s EA because the analysis in the EA 3826 was started in 2006. The commenter claims to have based the test probabilities used to 3827 make their estimates on a sample of 29 regist ration review cases (not new registrations) 3828 occurring between 2008 and 2010. 3829

v. Factors which drive costs for new registrations. To determine the influence of 3830 the previously-discussed factors on the di fference between the co mmenter’s and EPA’s 3831 estimates, EPA performed the following anal ysis on the data requirements costs and 3832 incremental costs using the same unit test costs and test probabilities used in the 3833 proposed rule: 3834*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 154 of 233  To account for the effect of the unit test costs on the data requirements costs 3835 and incremental costs, EPA substituted t he commenter’s unit test costs without 3836 overhead into EPA’s analysis of the proposed ru le using EPA’s test probabilities and 3837 number of registrations. If ther e were no changes, this would indicate that the test costs 3838 were not driving the differences in estimates. 3839

 To account for the effect of test probabilities and number of registrations, EPA 3840 substituted the commenter’s unit test costs with overhead into EPA’s analysis. In this 3841 case, the difference between the EPA’s and the commenter’s analysis is contained in 3842 the test probabilities and number of registrations. If there were no changes, this would 3843 indicate that the test pr obabilities and number of registrations were not driving the 3844 differences between the two analyses. Since the commenter includes overhead in their 3845 analysis, overhead was included in this compar ison to make other things equal so that 3846 the differences in test pr obabilities and number of registra tions could be isolated. 3847 vi. Results. The results of the fact or analysis are presented in the following 3848 Table 1. 3849 Table 1: Comparison of Data Requirement Costs and Factors for New Registrations 3850 Column Factors 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 ac cording 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 3851 Column A exhibits the data requirement s and incremental costs from EPA’s EA 3852 of the proposed rule. In column B, the data requirements and incremental costs are 3853 calculated using the commenter’s unit test costs without overhead cost s, but EPA’s test 3854*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 155 of 233 probabilities and number of registrations. Column C is the same as column B, but with 3855 overhead costs included. Finally, column D exhibits the data requirements and 3856 incremental costs with overhead as calculated by the commenter. 3857 The result of the first fact or analysis is demonstrated by comparing column A to 3858 column B. In this case, the difference betwe en the two columns is the unit test costs. 3859 Inserting the commenter’s unit test costs, without overhead, into the cost estimates with 3860 EPA’s test probabilities and number of registrations leads to over a 30 percent increase 3861 in data requirements cost and a nearly 100 percent increase in incremental costs. 3862 The result of the second factor analysis is demonstrated by comparing columns 3863 C and D. In this case, the difference between the two columns is in the test probabilities 3864 and number of registrations. While individual test probabilities may be different in EPA’s 3865 and the commenter’s analyses, the ov erall effect of the products of test probabilities and 3866 number of registrations, when summed with the unit test costs, including overhead, are 3867 similar in both of these analyses. The resu lting differences in data requirements cost 3868 and incremental costs are less than 2 perc ent and about 6 percent, respectively. 3869 Therefore, EPA concludes that any differences in test probabilities and number of 3870 registrations used as input parameters in the calculations do not have a significant 3871 effect on the total data requirement cost of new registrations. 3872 Comparisons across columns A, B, and C also provide information on the portion 3873 of the cost difference accounted for by over head costs. Columns A, B, and C compare 3874 the cost of data requirements using the unit test cost esti mates of EPA, and those of the 3875 commenter with and without overhead. The ov erhead costs account for more than one3876 half of the difference in the total cost of the data require ments, but less than 40 percent 3877 of the difference in incremental costs (the incremental cost is the increase costs 3878*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 156 of 233 between the baseline , (the existing data requirements in part 161 , and proposed part 3879 158, subpart W). 3880 From this comparison, EPA makes the following conclusions. First, differences 3881 in test probabilities and number of regist rations do not have a significant impact on the 3882 cost of the rule. Second, even if EPA and the commenter used the same probabilities 3883 and test costs, inclusion of overhead costs by the commenter would result in a 30 3884 percent difference in costs. Finally, w hen the overhead costs are removed from the 3885 commenter’s analysis, differences in unit test costs between EPA and the commenter 3886 account for most of the differences in the estimates of the cost of the rule for new 3887 registrations. 3888 vi. Revised test costs. In light of the results of the comparis on between EPA’s 3889 and the commenter’s EA, EPA sought to verify its unit test cost estimates. To examine 3890 the costs submitted by ACC, EPA re-survey ed the cost of conducting studies for 30 data 3891 requirements: The criteria for selecting which test’s cost to update included how the 3892 difference in estimates would impact on t he cost of the rule, the magnitude of the 3893 differences in estimates, and the age and so urce of EPA’s estimates. EPA’s data 3894 gathering methodology is reproducible, and based on actual data. EPA does not adjust 3895 the lab’s cost estimates, i.e., the costs ar e used as obtained from the laboratory. Under 3896 the Information Quality Act (IQA), EPA must ensure and maximize the quality, 3897 objectivity, utility, and integrity of the data used in its analyses. 3898 The re-surveyed test costs are used in the EA (economic analysis) for the final 3899 rule. EPA is using its cost estimates because it has revised its most relevant and oldest 3900 unit test cost estimate s. In addition, the commenter did not provide a basis or sufficient 3901 explanation that would meet the standards of the IQA to justif y EPA’s accepting the 3902 commenter’s costs. For addi tional information see respons e to comment 40.1 in the 3903*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 157 of 233 Response to Comments Document and the final economic analysis, both in the docket 3904 at http://www.regulations.gov

. 3905 B. Impact on Small Businesses 3906 1. Comment . A commenter claimed that EPA underestimated costs, is not fully 3907 complying with the Regulatory Flexibility Act (RFA) and t he Small Business Regulatory 3908 Enforcement Fairness Act (SBREFA), and must prepare an Initial Regulatory Flexibility 3909 Assessment (IRFA). In addition, the co mmenter argued that small businesses will be 3910 adversely affected, that there will be an "inc reased disparity betw een registrants and a 3911 more uneven playing field," and finally, t hat a SBREFA analysis should have been 3912 conducted. 3913 2. EPA’s response. EPA acknowledges that the co st of the data requirements 3914 would likely be a larger percentage of a sma ll business’s revenues, but did not find that 3915 the rule would have a significant adverse ec onomic impact on a subs tantial number of 3916 small firms. 3917 A regulatory flexibility anal ysis examines the type and number of small entities 3918 potentially subject to the rule, record keeping and compliance requirements, and 3919 significant regulatory alternatives, among ot her things. RFA, as amended by SBREFA, 3920 requires EPA to consider the economic impact of proposed rules on small entities. RFA 3921 requires EPA to prepare an IRFA for each proposed rule, when the rule will have a 3922 significant economic impact on a subst antial number of sm all entities. 3923 To comply with RFA, EPA did a retros pective analysis of what the additional 3924 costs would have been on actual new registra tions if the proposed rule had been in 3925 effect during 2000-2005. This analysis did not indicate a significant impact on a 3926 substantial number of small entities; instead, the analysi s indicated that 5 percent of 3927 small firms (25 out of 500) are likely to experience some impact and only 2.8 percent of 3928*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 158 of 233 small firms (14 out of 500) are likely to ex perience an economic impa ct of 3 percent or 3929 more of gross sales. Based on this analysi s, EPA certified that the proposed rule would 3930 not have a significant adverse economic impact on a substantial number of small firms. 3931 As a result, EPA did not have to conduct an IRFA nor convene a SBREFA Panel for the 3932 proposed part 158, subpart W rule. 3933 In the EA for the final rule, EPA re-est imated the SBREFA analysis with revised 3934 unit test costs and changes in data requirements. 3935

 About 23 small firms (almost 5%) are lik ely to experience an economic impact 3936 of 3% or more of gross sales, and 3937

 About 26 small firms, (over 5%) are lik ely to experience an economic impact of 3938 1% or more of gross sales. 3939 Hence, had these results been estimated at the proposal stage, EPA would still 3940 have concluded that there would not be a signi ficant impact on a substantial number of 3941 small entities. 3942 C. Cost of New Data Requirements on Registration Review 3943 1. Comment . A commenter stated that EPA has not accurately stated the 3944 potential costs and benefits, as required by Executive Order (EO) 12866. In particular, 3945 EPA has not included the impact of increment al costs of new data requirements on 3946 registration review, or the cost of consultations. The comm enter also claims that under 3947 the PRA, EPA should include the paperwork bur den costs of registration review for 3948 existing registrants. 3949 2. EPA’s response . EO 12866 requires the Agency to submit to OMB for review 3950 significant regulatory actions. EPA comp lied with EO 12866 during 2008 by submitting 3951 drafts of both the economic analysis and the proposed rule to OMB. The changes that 3952 were made to the proposed rule as the result of OMB’s review were included in the 3953*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 159 of 233 docket for the proposed rule at http://www.regulations.gov

. . The Agency notes that one 3954 purpose of soliciting comments on the economic analysis at the proposal stage is to get 3955 input on where the Agency might improve the economic analysis. 3956 The commenter is not correct in asserti ng that EPA did not include the impact of 3957 incremental costs. The Agency has capt ured the anticipated costs necessary for 3958 complying with the regulat ions. See the final Economic Analysis (Ref. 13 1 ) in the 3959 docket at for a more detailed discussion, particularly sections 5.3 and 5.5. 3960 The commenter is correct in that t he costs of fulfilling the 11 “new” data 3961 requirements during registrati on review were not considered in the Agency’s economic 3962 analysis of the proposed part 158, subpart W data requirement s. EPA agrees with the 3963 commenter that registrants of existing antimicrobial products will incur costs during 3964 registration review. In fact, EPA relied on the 2005 EA conducted for the Registration 3965 Review Rule. When registration review was proposed, EPA prepared an economic 3966 analysis of that program, wh ich estimated the cost of data requirements and paperwork 3967 burden according to what would likely be requi red in registration review for existing 3968 registrants. The 2005 registration review EA estimate of data requirement costs for 3969 existing antimicrobial pesticides was based on what would likely be required for a 3970 sample of antimicrobial active ingredients. This would have included all tests that would 3971 have been required at that time, i.e ., those in current practice whet her or not in part 158. 3972 However, the proposed part 158, subpart W included “new” tests, which were not 3973 anticipated when the economic analysis of the registration review process was 3974 completed. In a final economic analysi s for part 158, subpart W, EPA addresses the 3975 additional registration review costs for these 11 “new” studies , as well as other changes 3976 from the proposed rule to the final rule , including changes made as a result of the 3977 comments received. The incremental im pact for Registration Review is $ 6.8 M million

. 3978*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 160 of 233 The commenter is also correct that EPA did not include the cost of consultation in 3979 its economic analysis. Consultations are longstanding, commonly used, and valuable 3980 processes in EPA’s Pesticide Program and are beneficial to both EPA and the 3981 applicants. However, consultations are not mandatory, and based on comments 3982 received EPA has removed all references to consultations from the final data 3983 requirements tables. See Unit V.C

. for additional information on the use and purpose of 3984 consultations. 3985 XXIII. References 3986 As indicated under ADDRESSES , a docket has been established for this 3987 rulemaking under docket ID number EPA- HQ-OPP–2008–0110. The following is a 3988 listing of the documents that are specifically referenced in this proposed rule. The 3989 docket includes these documents and other information considered by EPA in 3990 developing this rule, including documents that are referenced within the documents that 3991 are included in the docket, even if the refere nced document is not physically located in 3992 the docket. For assistance in locating docum ents, please consult the technical contact 3993 listed under FOR FURTHER INFORMATION CONTACT

. 3994 Ref. 1 : Rule Text of . USEPA, Final Economic Analysis of Changes in Data 3995 Requirements for Antimicrobial Pesticides , (INSERT: date of FINAL EA after OMB 3996 review). 3997 2. USEPA, “Data Requirements for Pesticide Registration; Final Rule ;” ” (49 FR 3998 42856 , October 26, 2007)(FRL 8106-5 ). 3999 Ref. 2 : 3. ACC Biocides Panel; “Regulation of Antimicrobials that are Indirect or 4000 Secondary Direct Food Addi tives;” (February 2, 2006). 4001*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 161 of 233 Ref. 3 : ACC 4. CMA Biocides Panel; “Comments on EPA’s September 17, 1999 4002 Proposed Rule on Registration Requirements fo r Antimicrobial Pesticide Products and 4003 Other Pesticide Regulatory Changes for Codification; (January 18, 2000). 4004 Ref. 4: 5. ACC Biocides Panel; Memorandum to Frank Sanders, “EPA’s Current 4005 Interpretation of the Antimicrobial Reform Te chnical Corrections Act and Section 2(bb) 4006 of FIFRA is Inconsistent with the Statutes;” ( August November 3, 2000). 4007
Ref. 5: 6. ACC Biocides Panel; “EPA/FDA Jurisdiction for Food Contact 4008 Antimicrobials;” (July 17, 2003). 4009 Ref. 6: 7. Grizzle, Charles L.; representative of Albright & Wilson Americas, Inc., 4010 letter to Lynn R. Goldman; (September 11, 1997). 4011
Ref. 7: 8. ChemReg International, L.L.C.; Ti ered Testing for Risk Assessment of 4012 Antimicrobial Pesticides; (September 12, 2002). 4013
Ref. 8: 9. Goldberg, Seth; “Section 2(bb) of FI FRA; Dual Jurisdic tion Over Food 4014 Contact Antimicrobials; (April 27, 2001). 4015
Ref. 9: 10. ACC Biocides Panel; “Comments on The Preliminary Risk Assessment 4016 for 1,4-Bis(bromoacetoxy)-2- butene (BBAB);” (August 6, 2001). 4017 Ref

. 10: 11. ACC Biocides; Hasmukh C. S hah letter to Frank T. Sanders; 4018 (August 3, 2000). 4019 Ref. 1 1 : 12. Edwards, Deborah; OPP Respons e to CropLife letter of May 29, 4020 2009; (June 26, 2009). 4021 Ref. 12: 13. Overview of the Ecological Risk Assessment Process in the Office of 4022 Pesticide Programs, U.S. Environment al Protection Agency – Endangered and 4023 Threatened Species Effects De terminations (January 2004) ( see 4024 www.epa.gov/espp/consultati on/ecorisk-overview.pdf ). 4025 14. Portier; SAP Waiver; (April 4, 2011). 4026*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 162 of 233 Ref. 13: USEPA; Final Economic Analysis of Changes in Data Requirements for 4027 Antimicrobial Pesticides (update date after OMB review )

. 4028 XXIV. FIFRA Review Requirements 4029 In accordance with FIFRA sectio n 25(a), a draft of this final rule was submitted to 4030 the FIFRA Scientific Advisory Panel (SAP)

. SAP. EPA requested the FIFRA SAP to 4031 waive its review of the final rule based on fa ct that the SAP, in 2008, had waived review 4032 of the proposed rule: The final rule does not contain any new scientific issues 4033 warranting additional review by the SAP. The SAP waived its review on April 4, 2011, 4034 stating that “[t]he final rule does not contai n scientific issues that the Panel has not 4035 previously considered” (Ref. 12 14 ). 4036 In accordance with FIFRA section 25(a), EPA has submitted a draft of the final 4037 rule to the appropriate Congressional Commi ttees and the Secretar y of the Department 4038 of Agriculture. There were no comm ents in response to these submissions. 4039 In accordance with FIFRA section 21(b), EPA s ubmitted a draft of the final rule to 4040 the Secretary of Health and Human Services (HHS )

. Their comments on the draft of the 4041 final rule included requests to e xpand further the discussion on “ the differentiation of 4042 auth orities of the Food [and] Drug Admini stration (FDA) and EPA on regulation of 4043 antimicrobial pesticides when present in food , ” and also, various edits were requested 4044 by FDA’s Office of General Counsel (OGC). In response, EPA has expanded the 4045 differentiation discussion and made various edits. Both EPA’s OGC and FDA’s OGC 4046 vetted the changes. ), and that the agency’s comments were reviewed and addressed in 4047 this final rule. 4048 HHS also requested that EPA f urther clarify t he “guidance for product registrants 4049 in using emerging alternate test methods in evaluation of to xicity.” EPA agrees that 4050 because the science is changing rapidly, co ntinuous communication with stakeholders 4051*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 163 of 233 will be important to their understanding of the av ailability of alternat e test methods that 4052 OPP would consider. OPP established the PPDC workgrou p on 21st C entury 4053 T oxicology to support this communication. In formation on OPP's transition to alternate 4054 methods is available on EPA's website on OPP ’s 21st Century toxicology vision and 4055 strategy webpage , which contains a tool s matrix that describes plans to incorporate new 4056 scientific tools. 4057 FDA also noted that “the data requirement s do not appear to consider impacts of 4058 the proposed pesticide use on antimicr obial resistance development.” As discussed in 4059 the proposed rule, EPA is a participant on the Intera gency Task force on Antimicrobial 4060 Resistance. While the focus of this group is on the use of antibiotics, the Antimicrobials 4061 Division (AD) has participated in the taskforce efforts by providing review and comment 4062 on documents related to antimicrobial resi stance, specifically, t he reports of the Codex 4063 Ad Hoc Intergovernmental Task Force on Anti microbial Resistance, issued through the 4064 Codex Alimentarius Commission. AD also conducted a literature search into the use of 4065 antimicrobial pesticides and the develo pment of resistant bacteria . While this literature 4066 search is several years old, AD does not believe that there have been substantial 4067 changes since the search was conducted. 4068 The results of the literat ure search did not support a finding that the use of 4069 ant imicrobial pesticides leads to develop ment of resistant bacteria. EPA does consider 4070 the impacts of a pesticide's use on the development of antimicrobial resistance

. 4071 However, EPA is unaware of a data r equirement approach that would fit this 4072 circumstance. Antimicrobial resistance develops in th e environment during use, or as a 4073 result of the use when the micro

- organisms that are still pr esent "swap their genetic 4074 material." The efficacy studies required as part of the application submission provide 4075 informat ion on the product's ability to kill or deactivate the micro

- organism when used 4076*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 164 of 233 according to the directions on the product. Historically, the concentration of the 4077 antimicrobial in the product is set well

- over the minimum inhibito ry concentration, to 4078

assur e that the micro

- organism is killed or deactivated. If information indicated that an 4079 antimicrobial product was not performing effe ctively, then it is likely that the 4080 manufacturer would request an amendment to their registration to increase the 4081 concentrati on of the antimicrobial in the produc t. EPA has been unable to determine to 4082 what extent there is a problem of antimicrobial resistance or what data submitted as part 4083 of a registration package could predict t he environmental conditions for developing 4084 resis tance in the future. EPA therefore watches, monitors, and mitigates , as needed. 4085 XXV. Statutory and E xecutive Order Reviews 4086 A. Executive Order 12866: Regulatory Planning and Review and Executive Order 4087 13563: Improving Regulation and Regulatory Review 4088 Under Executive Order 12866 , entitled Regulatory Planning and Review (58 FR 4089 51735; October 4, 1993), this action is a “si gnificant regulatory action” because this 4090 action might raise novel legal or policy is sues arising out of legal mandates, the 4091 President’s priorities, or the principles set forth in the Executive Order. Accordingly, 4092 EPA submitted this action to the Office of Management and Budget (OMB) for review 4093 under Executive Orders 12866 and 13563 , entitled Improving Regulation and 4094 Regulatory Review (76 FR 3821; January 21, 2011). Any changes made in response to 4095 OMB recommendations have been documented in the docket for this action. 4096 EPA has prepared an EA of the potential costs associated with this action, 4097 entitled “Final Economic Analysis of Changes in Data Requirements for Antimicrobial 4098 Pesticides” (Ref. 13 1 ), a copy of which is in the docket at http://www.regulations.gov

. 4099 This final EA evaluates the potential benef its and costs expected as a result of 4100 registrations and registration reviews. The EA is briefly summarized here. 4101*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 165 of 233 In its analysis, the Agency considered the potential, additional costs for the 4102 registration of new antimicrobial pestici des or new uses of currently registered 4103 antimicrobial pesticides, as well as the pot ential, additional costs incurred during the 4104 registration review of existi ng antimicrobial pesticides. 4105 Based on comments received during the pub lic comment period, the following 4106 changes were made to the rulemaking, and ar e therefore reflected in the final EA: 4107

 One proposed data requirem ent will not be codified: Non-dietary ingestion 4108 exposure. The test cost is $75,000. In the proposed rule, EPA expected to receive the 4109 test 0.8 times per year, representi ng an annual industry savings of $63, 125. 4110

 EPA revised certain of the data requirem ents from “NR” or “CR” to “R,” or 4111 vice-versa. 4112

 Based on comments received, three new data requirements were added: 4113 Simulation test to assess t he biodegradability of chemicals discharged in wastewater, 4114 simulation test – aerobic sewage treatment: activated sludge units, and nature of the 4115 residue on surfaces. The rationale for thes e three new studies is described in Unit 4116 III. D B

. 4117 The estimated costs for both registration review and for a registration action for 4118 the three newly-required data requirements are: 4119 1

. Simulation tests to assess the biodegradability of chemicals in discharged 4120 wastewater and simulation te st – aerobic sewage treatmen t: activated sludge units

. 4121 Both of these studies are used as part of the down

- the

- drain analysis for 4122 antimicrobials. The studies ar e conditionally required for all use patterns, except for the 4123 aquatic areas use pattern, for which the study is not required. EPA does not have an 4124 estimate for the cost of either of these studies; instead, for the EA, EPA used the value 4125 $33,000, which is the cost of the porous pot test. The A gency expects, however, that 4126*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 166 of 233 the cost of the simulation tests will be less than this amount. For registration review, 4127 EPA expects to receive the porous pot test or one of the simulation tests up to 8.5 times 4128 per year, for an annual industry cost of $280, 500. For new registrations, EPA expects 4129 to receive either of the studies up to 7.5 times per year, for an annual industry cost of 4130 $247,500. The total annual cost is $528,000. 4131 2

. Nature of residue on surfaces . This test is part of the residue chemistry data 4132 requirements, and is conditionally required for all use pattern categories. The test cost 4133 is $95,000. For registration review, EPA expects to receive this test 1.3 times per year, 4134 for an annual industry cost of $118,750. For new registrations, EPA expects to receive 4135 this test up to 0.5 times per year, for an annual industry cost of $44,333. The total 4136 annual cost is $163,083. 4137 Many test notes for data require ments were revised based on comments 4138 received. Data requirements for certain us e patterns were changed from “NR” or “CR” 4139 to “R,” while others were changed from “R” to “CR.” Because the cost of the rule 4140 depends, in part, on the probabilities of the te sts being required, these revisions have 4141 resulted in a modification of t he cost of the rule. Instead of estimating the cost of each 4142 change individually, the Agency re -estimated the potential cost of the regulation as a 4143 whole, taking into account the changes discussed above previously

. 4144 Based on comments received, EPA has updated the unit test costs for 30 4145 selected tests. The criteria for selecti ng which test’s cost to update included: 4146

 How changing the cost estimates woul d impact on the cost of the rule, 4147

 The magnitude of the difference bet ween EPA’s cost estimate and the 4148 commenters’ cost estimate, and 4149

 The length of time since EPA’s cost estimate was last updated. 4150*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 167 of 233 EPA estimated the annual cost of register ing a new antimicrobial pesticide or 4151 new use of currently-registered antimicrobial pesticides, taking into account both the 4152 changes in data requirements and in unit test co sts. Both the tota l annual industry costs 4153 and the newly-imposed costs were estimat ed. The updated test costs plus exposure 4154 and other test costs revisions since the proposed rule increased the cost of the rule by 4155 about 23 percent compared to the proposed ru le. The estimated total annual industry 4156 costs of the final rule is expected to be about $19.3 million, whic h is approximately 29 4157 percent higher than the cost of the proposed rule. The difference between the baseline 4158 costs (the existing data requirem ents that were codified in 1984) and the cost of the 4159 Agency’s current practices is about $1 m illion annually. The difference between the 4160 baseline costs and the final rule costs, i.e., the incremental costs is approximately $8.2 4161 million annually. Under the final rule, the av erage cost per registra tion action of a new 4162 antimicrobial active ingredient is appr oximately $1 million to $5 million. 4163 For existing chemicals, data requirements in part 158 , subpart W are relevant to 4164 the registration review program which began to replace the reregistration program in 4165 2006 as a means of systematically reeval uating existing registrations against the 4166 standards of FIFRA. 4167 EPA has evaluated the impact of t he data requirements being codified today in 4168 this final rule on registrants of existing chemicals undergoing registration review whose 4169 active ingredient databases data bases do not contain all of the new data requirements. 4170 The average additional cost of registrati on review as a result of the new data 4171 requirements is estimated to be about $588, 000 for wood preservatives, $284,000 for 4172 food and indirect food uses, and $260,000 for all other uses. For registration review, 4173 the total annual cost is $6.8 million. 4174*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 168 of 233 As required, EPA conducted an analysis of the impact of this final rule on small 4175 businesses, as discussed in the Unit XXV.C. 4176 B. Paperwork Burdens Reduction Act (PRA) 4177 The information collection requirements contained in this rule have been 4178 submitted for approval to OMB under the P aperwork R eduction A ct ( PRA ) , , 44 U.S.C. 4179 3501 et seq . At the time of the proposed rule , EPA prepared a supporting statement for 4180 amending an ICR), entitled “Data Requirements for Antimicrobial Pesticides (Proposed 4181 Rule)” and identified by EPA ICR No. 2318.01, a copy of which is in the docket at 4182 http://www.regulations.gov

. . 4183 Under PRA, “burden” means the total time, effort, or financial resources 4184 expended by persons to generate, maintain, reta in, or disclose or provide information to 4185 or for a Federal agency. 4186 The information collection activities rela ted to the submission of data to EPA in 4187 order to register, amend or retain a new or existing pesticide product or obtain a 4188 tolerance for that product are already appr oved by OMB under PRA. As such, the 4189 supporting statement only addr esses the proposed changes to the data requirements 4190 that impact the information collection activiti es related to antimicrobial pesticides. The 4191 procedures for submitting data to EPA under FIFRA and FFDCA are not changed in this 4192 proposal, and are already approved by OMB in the following ICRs: 4193

 Tolerance ICR. Data Submission Activiti es Associated with Tolerance 4194 Actions (currently approved under OMB Cont rol No. 2070-0024 (EPA ICR No. 0597)); 4195

 Registration ICR. Data Submission Activities A ssociated with the Application 4196 for a New or Amended Registration of a Pesticide (currently approved under OMB 4197 Control No. 2070-0060 (EPA ICR No. 0277)); and 4198*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 169 of 233  Reregistration, Special and Registration Review ICR. Data Submission 4199 Activities Associated with the Generation of Data for Special Review or Registration 4200 Review (currently approved under OMB Control No. 2070-0174 (EPA ICR No. 2288)). 4201 These three program activities are an integral part of the Agency’s pesticide 4202 program, including antimicrobial pesticides, and the corresponding ICRs are regularly 4203 renewed every 3 years as required by PRA. The total estimated average annual public 4204 reporting burden currently approved by OMB for these various activities range from 8 4205 hours to approximately 3,000 hours per respo ndent, depending on the activity and other 4206 factors surrounding the particular pesticide product. 4207 In the supporting statement the Agency esti mates that the typical, current annual 4208 paperwork burden for registrants per antimicrobial pesticide registration is 194 burden 4209 hours and $12,631. The total annual registr ant paperwork burden and costs for data 4210 submission activities for antimicrobial pesticides applicants and registrants will be 4211 updated accordingly in the ICRs specified above in this discussion during the next, 4212 appropriate ICR renewal cycle. 4213 An agency may not conduct or sponsor, and a person is not required to respond 4214 to an information collection request unless it displays a currently valid OMB control 4215 number, or is otherwise required to submit the specific information by a statute. The 4216 OMB control numbers for EPA’s regulations codi fied in Title 40 of the Code of Federal 4217 Regulations, after appearing in the preamble of the final rule, are further displayed 4218 either by publication in the Federal Register or by other appropriate means, such as on 4219 the related collection instrum ent or form, if applicable. The display of OMB control 4220 numbers for certain EPA regulations is consolidated in a lis t at 40 CFR 9.1. 4221 C. Small Entity Impacts 4222 The Regulatory Flexibility Act (RFA) 4223*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 170 of 233 The RFA, 5 U.S.C. 601 et seq ., generally requires an Agency to prepare a 4224 regulatory flexibility analysis of any rule subject to notice and comment rulemaking 4225 requirements under the Administrative Proc edure Act or any other statute unless the 4226 agency certifies that the rule will not have a significant econom ic impact on a substantial 4227 number of small entitie s. Small entities include small businesses, small organizations 4228 and small governmental jurisdictions. 4229 For purposes of assessing the impacts of today's this final rule on small entities, 4230 small entity is defined as: 4231 ( 1 )

. A small business as defined by the Sm all Business Administration’s (SBA) 4232 regulations at 13 CFR 121.201, which is based on either the maximum number of 4233 employees or on the sales for small businesse s in each industry sector, as defined by a 4234 6-digit NAICS code, and for this rule is a producer of pesticide products (NAICS 32532), 4235 antifoulants (NAICS 32551), antimicrobial pesticides (NAICS 32561) or wood 4236 preservatives (NAICS 32519), importers of such products, or any person or company 4237 who seeks to register an antim icrobial, antifoulant coating, ballast water treatment, or 4238 wood preservative pesticide or to obtai n a tolerance for such a pesticide; 4239 ( 2 )

. A small governmental jurisdiction that is a government of a city, county, town, 4240 school district or special district with a population of le ss than 50,000; or 4241 ( 3 )

. A small organization that is any not-for-profit enterprise which is 4242 independently owned and oper ated and is not dominan t in its field. 4243 After considering the economic impacts of th is final rule on small entities, I certify 4244 that this action will not have a significant adverse economic impact on a substantial 4245 number of small entities. T he factual basis for the Agency’s determination is presented 4246 in the small entity impact analysis prepared as part of the Economic Analysis for this 4247 final rule (Ref. 13 1 ), which is available in the docket at http://www.regulations.gov

. . 4248*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 171 of 233 EPA has determined that this rulemaking does not impact any small governmental 4249 jurisdictions or any small non-for-profit ent erprise because these entities are rarely 4250 pesticide applicants or registrants. As such, EPA has assessed the impacts on small 4251 businesses. Some of the small entities direct ly regulated by this rulemaking are in the 4252 pesticide and other agricultural chemical ma nufacturing industry sector (NAICS code 4253 325320). Firms in this sector are consider ed small under the SBA definition if they 4254 employ 500 or fewer people. The economic analysis for the final rule specifies the 4255 NAICS code used for each of the firms analyzed. 4256 EPA estimates that 750 unique parent com panies constitute the total universe of 4257 pesticide antimicrobial regist rants. Of these, based on the SBA definition of a small 4258 business and the available sales data for these firms, EPA estimates that 500, or 4259 approximately 67 percent, qualify as a sma ll business. When considering both 4260 registration review and new registrati ons, on average each year about 30 small 4261 businesses would have incurred additional cost s under this rule. EPA estimates that: 4262

 About 23 small firms (almost 5 percent of the 500 small antimicrobial firms ) 4263 subject to this regulation ar e likely to experience an economic impact of 3 percent or 4264 more of gross sales, 4265

 About 3 small firms (0.6 percent of the 500 small antimicrobial firms ) subject 4266 to this regulation are likely to experienc e an economic impact of greater than 1 percent 4267 but less than 3 percent of sales revenues, and 4268

 About 3 small firms (0.6 percent of the 500 small antimicrobial firms ) subject 4269 to this regulation are likely to experienc e an economic impact of greater than 0 percent, 4270 but less than 1 percent of sales revenues. 4271 In addition, there are also opportunities for small entities to lower their potential 4272 costs. The proposed data requi rements in many instances are tiered, with higher-tiered 4273*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 172 of 233 testing triggered on the results of lower-tie red testing. EPA encour ages registrants to 4274 consult with the Agency to ensure that only the required data is submitte d. If available, 4275 open literature or the same test s on similar products, or alte rnative means to meet data 4276 requirements, such as QSAR, can be submitt ed for Agency consideration. Some firms 4277 may have surrogate data or they may share the cost of generating data. These may 4278 present opportunities for cost savings by sma ll entities, and all other applicants as well, 4279 while allowing the Agency to fulfill its role of making pesticide regul atory decisions that 4280 protect the general populat ion, sensitive sub-populat ions, and the environment. 4281 T h is rule was propo sed on October 8, 2008

. Small entities were able to provide 4282 comments during the 90 day pub lic comment period, which was extended an additional 4283 90 days at the reques t of stakeholders. On November 6, 2008, EPA convened a public 4284 workshop to explain the prov isions of the proposed rule, arranging for the workshop to 4285 be webcast for those who could not a ttend the public workshop in person. 4286 D. Unfunded Mandates 4287 Under Title II of the Unfunded Mandates Reform Act of 1995 (UMRA) ( 2 U.S.C. 4288 1531

- 1538 ), 4289 Title II of UMRA, 2 U.S.C. 1531-1538, establishes requirements for Federal 4290 agencies to assess the effects of their regul atory actions on State, local, and tribal 4291 governments and the private sector. EPA has determined that this final rule does not 4292 contain a Federal mandate that may result in expenditures of $100 million or more for 4293 State, local, and tribal gover nments, in the aggregate, or t he private sector in any one 4294 year. As described in Unit XXV.A , ., the incremental costs for th is final rule is estimated 4295 at approximately $8.3 million (for registration actions) and $6.8 million (for registration 4296 review) per year for the private sector, whic h is below the $100 million threshold. Since 4297 State, local, and tribal gover nments are rarely pesticide applicants, this rule is not 4298*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 173 of 233 expected to significantly or uniquely affect sma ll governments. Accordingly, this rule is 4299 not subject to the requirements of sections 202 and 205 of UMRA. 4300 This rule is also not subject to the requirements of section 203 of UMRA because 4301 it contains no regulatory requi rements that might significant ly or uniquely affect small 4302 governments. As stated above previously , State, local, and tribal governments are rarely 4303 pesticide applicants. 4304 E. E. Executive Order 13132: Federalism 4305 This action does not have federalism implications, because it will not have 4306 substantial direct effects on the States, on the relationship between the national 4307 government and the States, or on the distribution of pow er and responsibilities among 4308 the various levels of government, as specif ied in Executive Order 13132 (64 FR 43255; 4309 August 10, 1999)

. Since States or local governments ar e rarely pesticide applicants or 4310 registrants, this final rule would seldom affect a State or local government. Thus, 4311 Executive Order 13132 does not apply to this rule. 4312 In the spirit of Executive Order 1 3132 and consistent with EPA policy to promote 4313 communication between EPA, and State and local governments, EPA specifically 4314 solicited comment on the proposed rule from State and local officials. EPA did receive 4315 comments on substantive parts from loca l sanitation districts and associations 4316 representing their interest s. Their comments are addre ssed in the Response to 4317 Comments Document in the docket at http://www.regulations.gov , and, as appropriate, 4318 revisions were made for the final rule. 4319 F. F. Executive Order 13175: Cons ultation and Coordination with Indian Tribal 4320 Government Implications 4321 This action does not have tribal implicat ions, as specified in Executive Order 4322 13175 (65 FR 67249, November 9, 2000)

. At present, no tribal go vernment holds, or 4323*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 174 of 233 has applied for, a pesticide registration. T hus, Executive Order 13175 does not apply to 4324 this action. In the spirit of the Order, and consist ent with EPA policy to promote 4325 communications between the Agency and Indi an tribes, EPA specifically solicited 4326 comment on the proposed rule from tribal o fficials. No comments were received. 4327 G. Protection of Children’s Health 4328 This final rule is not subject to Executive Order 13045 , entitled : Protection of Children 4329 from Environmental Health Risks and Safety Risks (62 FR 19885, April 23, 1997) 4330 because

. 4331 EPA interprets Executive Order 13045 (62 FR 19885, April 23, 1997), as 4332 applying only to those regulatory actions that concern health or safety risks, such that 4333 the analysis required under section 5-501 of t he Executive Order has the potential to 4334 influence the regulation. This final rule is not subject to Ex ecutive Order 13045because 4335 it is not economically significant as def ined by Executive Order 12866, and because the 4336 Agency does not have reason to believe the environmental health or safety risks 4337 addressed by this action present a disproporti onate risk to children. This rule does not 4338 propose an environmental standard that is intended to have a negatively 4339 disproportionate effect on childr en. To the contrary, this rule is intended to provide 4340 added protection to children from antimicrobial pesticide risk. EPA will use the data and 4341 information obtained by this action to carry ou t its mandate under FFDCA to give special 4342 attention to the risks of pesticides to sens itive groups in early lifestages, especially 4343 infants and children. 4344 H. Executive Order 13211: Actions Concerni ng Regulations that Significantly Affect 4345 Energy Supply, Distr ibution, or Use 4346 This final rule is not subject to Executive Order 13211 , entitled Actions 4347 Concerning Regulations that Significantly Affect Energy Supply, Distribution, or Use (6 4348*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 175 of 233 (66 FR 28355, May 22, 2001) because it is not an economically significant regulatory 4349 action under Executive Order 12866, and it is not likely to have any adverse effect on 4350 the supply, distribution, or use of energy. 4351 I. National Technology Transfer and Advancement Act (NTTAA) 4352 Section 12(d) of the National Technology Transfer and Advancement Act of 1995 4353 (“ NTTAA ”), Public Law No. 104

- 113, 12(d) ( , 15 U.S.C. 272 note ) , directs EPA to use 4354 voluntary consensus standards in its regulat ory activities unless to do so would be 4355 inconsistent with applicable law or other wise impractical. Voluntary consensus 4356 standards are technical standards (e.g., ma terials specifications, test methods, 4357 sampling procedures, and business practices) that are developed or adopted by 4358 voluntary consensus standards bodies. NTTAA directs EPA to provide Congress, 4359 through OMB, explanations when the A gency decides not to use available and 4360 applicable voluntary consensus standards. Th is action does not involve technical 4361 standards. Therefore, EPA did not consider the use of any voluntary consensus 4362 standards. 4363 J. Environmental Justice 4364 Executive Order 12898 entitled : Federal Actions to Address Environmental 4365 Justice in Minority Populations and Low

- Income Populations 4366
Executive Order 12898 (59 FR 7629; February 16, 1994) establishes federal 4367 executive policy on environmental justice. Its main provision directs Federal agencies, 4368 to the greatest extent practicable and permitt ed by law, to make environmental justice 4369 part of their mission by ident ifying and addressing, as approp riate, disproportionately 4370 high and adverse human health or environmental e ffects of their progr ams, policies, and 4371 activities on minority populations and low-in come populations in the United States. 4372*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 176 of 233 EPA has determined that this final rule will not have disproportionately high and 4373 adverse human health or environmental effect s on minority or low-income populations 4374 because it increases the level of environmen tal protection for all affected populations 4375 without having any disproportionately high and adverse human healt h or environmental 4376 effects on any population, includ ing any minority or low-inco me population. This rule 4377 only impacts entities that intend to register or currently hold a registration for an 4378 antimicrobial pesticide. 4379 XXVI. Congressional Review Act 4380 The Congressional Review Act, 5 U.S.C. 801 et seq ., generally provides that before a 4381 rule may take effect, the Agen cy promulgating the rule must s ubmit a rule report to each 4382 House of the Congress and the Comptroller General of the Unit ed States. EPA will 4383 submit a report containing this rule and other required information to the U.S. Senate, 4384 the U.S. House of Represent atives, and the Comptroller G eneral of the United States 4385 prior to publication of the rule in the Federal Register . This rule is not a “major rule” as 4386 defined by 5 U.S.C. 804(2). 4387 List of Subjects in 40 CFR Part 158 4388 Environmental protection, Administrative practice and proc edure, Agricultural 4389 commodities, Pesticides and pests, Repor ting and record keeping requirements. 4390 List of Subjects in 40 CFR Part 161 4391 Environmental protection, Administrati ve practice and procedure, Agricultural 4392 commodities, Pesticides and pests, Repor ting and record keeping requirements. 4393 Dated: ______________ 4394

______________________ 4395 Administrator 4396*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 177 of 233 Therefore, 40 CFR pa rt 158 and part 161 are amended as follows: 4397 4398 1. PART 158 [AMENDED} 4399 1. The authority citation for part 158 continues to read as follows: 4400 Authority: 7 U.S.C. 136-136y and 21 U.S.C. 346a. 4401 2. Revise § 158.1(c)(4) to read as follows: 4402 § 158.1 Purpose and scope. 4403

***** 4404 * * * * * 4405 (c ) *** )* * * 4406 (4) Antimicrobial pesticides. Subparts A, B, C, D, and W of this part apply to 4407 antimicrobial pesticides. 4408 3. In § 158.100 revise the heading of paragraph (a); revise paragraph (b); 4409 redesignate paragraph (c) as paragraph (e); and add new paragraphs (c) and (d) to 4410 read as follows: 4411 § 158.100. Pesticide use patterns. 4412 (a ). ) General use patterns for conventi onal, biochemical, and microbial 4413 pesticides

. ***

. *** 4414 (b) Pesticide use site index for convent ional, biochemical, and microbial 4415 pesticides. The Pesticide Use Site Index for Conv entional, Biochemical, and Microbial 4416 Pesticides is a comprehensive list of spec ific pesticide use sites. The index is 4417 alphabetized separately by site for all agr icultural and all nonagricultural uses. The 4418 Pesticide Use Site Index associates each pes ticide use site with one or more of the 12 4419 general use patterns. It may be used in co njunction with the data tables to determine 4420 the applicability of data requirements to specif ic uses. The Pesticide Use Site Index for 4421 Conventional, Biochemical, and Microbial Pe sticides will be updated periodically, and is 4422*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 178 of 233 available from the Agency or may be obt ained from the A gency's website at 4423 http://www.epa.gov/pesticides

. 4424 (c) Antimicrobial pesticide use patterns. The general use patterns for 4425 antimicrobial pesticides ar e described in § 158.2201. 4426 (d) Pesticide use site index for antimicrobial pesticides. The Pesticide Use Site 4427 Index for Antimicrobial Pestici des is a comprehensive list of specific antimicrobial use 4428 sites. The index is alp habetized by antimicrobial use sites, and associates each 4429 antimicrobial use site with one or more of the antimicrobial use patterns. It may be used 4430 in conjunction with the data tables to determi ne the applicability of data requirements to 4431 specific uses. The Pesticide Use Site Index for Antimicrobial Pesticides will be updated 4432 periodically, and is available from the A gency or may be obtained from the Agency’s 4433 website at http://www.epa.gov/pesticides

. 4434 (e) *** 4435 * * * * * 4436 §158.400 [Amended] 4437 4. In the table in § 158.400(d) remove the category heading “Efficacy of 4438 Antimicrobial Agents,” and all of the entries 91-2 through 91-8 under that category. 4439 5. Part 158 is amended by revis ing Revise subpart W to read as follows: 4440 Subpart W--Antimicrobial P esticide Data Requirements 4441 Sec. 4442 §158.2200 Applicability. 4443 §158.2201 Antimicrobial use patterns. 4444 §158.2203 Definitions. 4445 §158.2204 Public health and nonpublic health claims. 4446 §158.2210 Product chemistry. 4447 §158.2220 Product performance. 4448 §158.2230 Toxicology. 4449 §158.2240 Nontarget organisms. 4450 §158.2250 Nontarget pl ant protection. 4451 §158.2260 Applicator exposure. 4452 §158.2270 Post-applicat ion exposure. 4453*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 179 of 233 §158.2280 Environmental fate. 4454 §158.2290 Residue chemistry. 4455 § 158.2200 Applicability. 4456 Part 158, subpart W estab lishes data requirements for any pesticide product that 4457 is: 4458 (a) A pesticide that is intended for use as an “antimicrobial pesticide” within the 4459 meaning of FIFRA sec. 2(mm)(1)(A ), regardless of whether it also meets the criterion of 4460 FIFRA sec. 2(mm)(1)(B). That criterion ex cludes from the definit ion any antimicrobial 4461 product that is intended for a food-use requiring a tolerance or exemption under FFDCA 4462 sec. 408 or a food additive regulation or clearance under FFDCA sec. 409. EPA will 4463 apply this subpart to all products intended for an antimicrobial use, purpose or function; 4464 the exclusion in FIFRA sec. 2(mm)(1)(B) does not ex clude products fr om the data 4465 requirements of this subpart. 4466 (b) A product that bears both antimicrobial and non-antimicrobial uses or claims. 4467 Such a product is subject to the data requi rements for pesticides in subparts C

– through 4468 O, and U or V of this part with respect to its non-antimicrobial uses and claims, and to 4469 the requirements of this subpart W with respect to its antimicrobial uses and claims. 4470 (c) A wood preservative, including a product that is intended to prevent wood 4471 degradation problems due to fungal rot or decay, sapstain, or molds. 4472 (d) An antifoulant, including a product t hat is intended to k ill or repel organisms 4473 that can attach to underwater surfaces, such as boat bottoms. 4474 § 158.2201 Antimicrobial use patterns. 4475 (a) Antimicrobial use patterns . The 12 general use patterns used in the data 4476 tables in this subpart are: 4477 (1) Agricultural premises and equipment. 4478 (2) Food-handling/storage establis hments, premises and equipment. 4479*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 180 of 233 (3) Commercial, institutional a nd industrial premises and equipment. 4480 (4) Residential and public access premises. 4481 (5) Medical premises and equipment. 4482 (6) Human drinking water systems. 4483 (7) Materials preservatives. 4484 (8) Industrial proce sses and water systems. 4485 (9) Antifoulant paints and coatings. 4486 (10) Wood preservatives. 4487 (11) Swimming pools. 4488 (12) Aquatic areas. 4489 (b) Use site index . The Pesticide Use Site Index fo r Antimicrobial Pesticides is a 4490 comprehensive list of specific antimicrobi al use sites. The Index associates 4491 antimicrobial use sites with one or more of the 12 antimicrobial use patterns. It is to be 4492 used in conjunction with the data tables in th is subpart to determine the applicability of 4493 data requirements to specific uses. The An timicrobial Pesticide Use Site Index, which 4494 will be updated periodically, is available from the Agency or may be obtained from the 4495 Agency’s website at http://www.epa.gov/pesticides. 4496 § 158.2203 Definitions. 4497 Definitions . The following terms are defined for the purposes of this subpart: 4498 Disinfectant means a substance, or mixture of substa nces, that destroys or irreversibly 4499 inactivates bacteria, fungi and vi ruses, but not necessarily bact erial spores, in the inanimate 4500
environment. 4501 Fungicide means a substance, or mixture of subs tances, that destroys fungi (including 4502 yeasts) and fungal spores pathogeni c to man or other animals in the inanimate environment. 4503*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 181 of 233 Microbiological water purifier means any unit, water treatment product or system that 4504 removes, kills or inactivates all types of disease-causing microorganisms from the water, 4505 including bacteria, viruses and protozoan cysts, so as to render the treated water safe for 4506 drinking. 4507 Sanitizer means a substance, or mixture of s ubstances, that reduces the bacteria 4508 population in the inanimate environment by significant numbers, (e.g., 3 log 10 redu ction) or more, 4509 but does not destroy or eliminate all bacteria. Sanitizers meeting Public Health Ordinances are 4510 generally used on food contact surfaces a nd are termed sanitizing rinses. 4511
Sterilant means a substance, or mixture of substances, that destroys or eliminates all 4512
forms of microbial life in the inanimate enviro nment, including all forms of vegetative bacteria, 4513 bacterial spores, fungi, funga l spores, and viruses. 4514
Tuberculocide means a substance, or mixture of subs tances, that destroys or irreversibly 4515
inactivates tubercle bacilli in the inanimate environment. 4516
Virucide means a substance, or mixture of subs tances, that destroys or irreversibly 4517
inactivates viruses in th e inanimate environment. 4518 § 158.2204 Public health a nd nonpublic health claims. 4519 (a) Public health claim . An antimicrobial pesticide is c onsidered to make a public health 4520 claim if the pesticide product bears a claim to c ontrol pest microorganisms that pose a threat to 4521 human health, and whose presence cannot readil y be observed by the user, including but not 4522 limited to, microorganisms infectious to man in any area of the inanimate environment. A 4523 product makes a public health claim if one or more of the following apply: 4524 (1) A claim is made for control of specific microorganisms that are di rectly or indirectly 4525 infectious or pathogenic to man (or both ma n and animals). Examples of specific 4526 microorganisms include, but are not limited to : , : Mycobacterium tuberculosis , Pseudomonas 4527 aeruginosa , Escherichia coli (E. coli), human immunodefic iency virus (HIV), Streptococcus, and 4528*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 182 of 233 Staphylococcus aureus . Claims for control of microorgani sms infectious or pathogenic only to 4529 animals (such as canine distemper virus or hog c holera virus) are not c onsidered public health 4530
claims. 4531 (2) A claim is made for the pesticide product as a sterilant, di sinfectant, virucide, 4532 sanitizer, or tuberculocide agai nst microorganisms that are inf ectious or pathogenic to man. 4533 (3) A claim is made for the pesticide produc t as a fungicide agains t fungi infectious or 4534 pathogenic to man, or the product do es not clearly state that it is intended for use only against 4535 nonpublic health fungi. 4536 (4) A claim is made for the pesticide product as a microbiological water purifier or 4537 microbial purification system. 4538 (5) A non-specific claim is made that the pesticide product will beneficially impact or 4539 affect public health at the site of use or in the environmen t in which it is applied, and: 4540 (i) The pesticide product contains one or mo re ingredients that, under the criteria in 40 4541 CFR 153.125(a), is an active ingred ient with respect to a public health microorganism and there 4542 is no other functional purpose for the ingredient in the product; or 4543 (ii) The pesticide product is similar in composition to a re gistered pesticide product that 4544 makes antimicrobial public health claims. 4545 (b) Nonpublic health claim . An antimicrobial pestici de is considered to make a 4546 nonpublic health claim if the pesticide product bears a claim to control microorganisms 4547 of economic or aesthetic significance, w here the presence of th e microorganism would 4548 not normally lead to infection or disease in humans. Examples of nonpublic health 4549 claims include, but are not limited to , : Algaecides, slimicides, preservatives and 4550 products for which a pesticidal claim with respect to odor sources is made. 4551 §158.2210 Product chemistry. 4552*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 183 of 233 The product chemistry dat a requirements of subpart D of this part apply to 4553 antimicrobial products covered by this subpart. 4554 §158.2220 Product performance. 4555 (a) General. (1) Product performance requirement for all antimicrobial 4556 pesticides . Each applicant must ensure through te sting that his product is efficacious 4557 when used in accordance with label dire ctions and commonly accepted pest control 4558 practices. The Agency may require, on a case-by-case basis, submission of product 4559 performance data for any pesticide product r egistered or proposed for registration or 4560 amendment. 4561 (2) Product performance data for each product that bears a public health claim

. 4562 Each product that bears a public health cl aim, as described in §158.2204(a), must be 4563 supported by product performance data, as listed in the tabl e in paragraph (c) of this 4564 section. Product performance data must be submitted with any application for 4565 registration or amended registration. 4566 (3) Product performance data for each pr oduct that bears a nonpublic health 4567 claim. Each product that bears a nonpublic health claim, as described in §158.2204(b), 4568 must be supported by product performance data. Each registrant must ensure through 4569 testing that his product is efficacious when used in accordance with label directions and 4570 commonly accepted practices. The Agency rese rves the right to r equire, on a case-by4571 case basis, submission of product per formance data for any pesticide product 4572 registered or proposed for registration or amendment. 4573 (4) Determination of data requirements . Subpart B of this part and §158.2201 4574 describe how to use the table in paragraph (c ) of this section to determine the product 4575 performance data requirements for ant imicrobial pesticide products. 4576 (b) Key. R = Required; EP = End-use product. 4577*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 184 of 233 (c) Antimicrobial product performance data requirements table. 4578 The following table shows the data r equirements for antimicrobial product 4579 performance. 4580 Table -- Antimicrobial Product Pe rformance Data Requirements 4581 Guideline Number Data Requirement All Use Patterns Test Substance 810.2100 Sterilants – Efficacy Data Recommendations R EP 810.2200 Disinfectants for Use on Hard Surfaces – Efficacy Data Recommendations R EP 810.2300 Sanitizers for Use on Hard Surfaces – Efficacy Data Recommendations R EP 810.2400 Disinfectants and Sanitizers for Use on Fabrics and Textiles -- Efficacy Data Recommendations R EP

810.2500 Air Sanitizers – Efficacy Data Recommendations R EP 810.2600 Disinfectants for Use in Water -- Efficacy Data Recommendations R EP 4582 §158.2230 Toxicology. 4583 (a) General. Subpart B of this part and § 158.2201 describe how to use the 4584 table in paragraph (g) of this section to det ermine the toxicology data requirements for 4585 an antimicrobial pesticide product. Notes t hat apply to an individual test including 4586 specific conditions, qualificat ions, or exceptions are list ed in paragraph (h) of this 4587 section. 4588 (b) Uses. The applicant for registration must first determine whether the use is 4589 likely to result in pesticide residues in food or water and therefore consult the “Food 4590 Use” columns of the table in paragraph (g) of this section. Generally, if the residues of 4591 the antimicrobial result from an application to a surface or if

incorporated into a material 4592 that may come into contact with food or feed, and residues may be expected to transfer 4593 to such food or feed, then the “Indirect Food Uses” columns is to be consulted. 4594 (c) Tiering of data requirements. Applicants for regist ration of antimicrobials 4595 may perform tests in a tiered fashion. Afte r the initially required tests are conducted, 4596*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 185 of 233 additional testing may be required if results of the initial tests trigger the need for 4597 additional data. Conditions that trigger t he need for additional data are given in the test 4598 notes in paragraph (h) of this section. 4599 (d) 200 ppb. The 200 ppb level was originally used by the Food and Drug 4600 Administration with respect to the concentration of residues in or on food for tiering of 4601 data requirements for indirect food use biocides. The Agency has also adopted this 4602 same residue level for determining toxicology data requirements for indirect food uses 4603 of antimicrobial pesticides. The 200 ppb leve l is the concentration of antimicrobial 4604 residues in or on the food item. 4605 (e) Use of OSHA standards. If EPA determines that industrial standards, such as 4606 the workplace standards set by the Occupat ional Safety and Health Administration , 4607 (OSHA standards), provide adequate protection for a pa rticular pesticide or a particular 4608 use pattern, additional toxicity data may not be required for that pesticide or the use 4609 pattern. 4610 (f) Key. R = Required; CR = Conditionally required; NR = Not required; MP = 4611 Manufacturing-use product; EP = End-use product; TGAI = Technical grade of the 4612 active ingredient; TEP = Typical end-use pr oduct; PAI = Pure active ingredient; PAIRA = 4613 Pure active ingredient, radiolabeled; Choice = choice of several test substances 4614 depending on studies required. 4615***Deliberative Internal DocumentEO 12866 Draft– Do Not Cite, Quote,or Release***During Review ***Page186of233(g)Table.Antimicrobial toxicologydata requirements table.The following table shows the data requirements for4616toxicology. The test notesapplicable to the data requirements in this tableappear in paragraph (h) of this section.4617Table -- Antimicrobial Toxicology Data Requirements4618GuidelineNumberData RequirementFood Uses Nonfood Uses Test Substance Test NoteNo.DirectFoodUsesIndirectFood Uses(> 200 ppb)IndirectFood Uses(≤200 ppb)Swimming Pools,Aquatic Areas,Wood Preservatives,Metal Working FluidsAll 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 - rat R R R R R MP andTGAIEP andTGAI2, 4870.2400 Primary eye irritation - rabbit R 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 - rodent RR 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 dermal toxicity CRCR CR CR CR TGAI EP andTGAI12, 13870.325090-Day dermal toxicity CRCR CR 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 - rat R 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 – two rodentR R CR R CR TGAI TGAI 19, 21, 22*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***Page 187 of 233species – rat and mousepreferredDevelopmental Toxicity and Reproduction870.3700 Prenatal developmentaltoxicity - rat and rabbitpreferredRR R R R TGAI TGAI 23, 24, 25,26870.3800 Reproduction and fertilityeffectsR R R R R TGAI TGAI 26, 27, 28,29870.6300 Developmental neurotoxicity CR CRCR CR CR TGAI TGAI 28, 29, 30Mutagenicity870.5100Reverse mutation assayRR R R R TGAI TGAI 31, 32870.5300870.5375In vitromammalian genemutationR 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 animal safety CRCR CR CR CR NR Choice 36870.7600 Dermal penetration CR CRCR CR CR Choice Choice 3, 37870.7800 Immunotoxicity R R R R R TGAI TGAI 84619( h) Test notes. The following test notes appl y to the data requirements in 4620 the table to paragraph (g) of this section: 4621 1. Not required if test material is a gas or highly volatile liquid. 4622 2. The six end-use product (EP) acut e toxicity studies are required using 4623 the product as formulated for sale and distri bution. In addition, if the EP label 4624 has directions for diluting the produc t, then, the applicant may also need to 4625 conduct certain of the acute toxicity st udies using the highest concentration 4626 labeled for dilution (i.e. the least diluted pr oduct). The end-use dilution testing is 4627 in addition to the testin g conducted on the EP. 4628 3. Not required if test material is corrosive to skin or has pH less than 2 or 4629 greater than 11.5. 4630 4. Data are required when the product consists of, or under conditions of 4631 use will result in, a respirable material (e.g., gas, vapor, aerosol or particulates). 4632 5. Data are required if repeated derma l exposure is likely to occur under 4633 conditions of use. 4634 6. For indirect food uses ≤ 200 ppb, and all other nonfood uses, data are 4635 required if the neurotoxicity screen in the 90-day oral r odent study or other data 4636 indicate neurotoxicity. 4637 7. The 90-day dermal toxicity study and/or 90-day inhalation toxicity study 4638 are required if the Agency determines t hat dermal and/or inhalation exposure is 4639 the primary route of exposure. 4640 8. All 90-day subchronic studies in the rodent can be designed to 4641 simultaneously fulfill the requirements of the 90-day neurot oxicity and/or 4642*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

*** Deliberative Internal Document

– Do NOT Cite, Quote, or Release *** immunotoxicity studies by adding separat e groups of animals for testing of 4643 neurotoxicity and/or immunot oxicity param eters. 4644 9. The 90-day study is required in the rodent for hazard characterization 4645 (possibly endpoint selection) and dose- setting for the chronic/carcinogenicity 4646 study. It is not required in the mo use, but the Agency would encourage the 4647 applicant to conduct a 90-day range findi ng study for the purposes of dose 4648 selection for the mouse carcinogenicity study to achieve adequate dosing and an 4649 acceptable study. 4650 10. A 1-year non-rodent study (i.e., 1-year dog study) may be required if 4651 the Agency finds that a pesticide chemical is highly bioaccumulative and slowly 4652 eliminated. EPA may also require the appropriate metabolism and 4653 pharmacokinetic studies to evaluate more precisely bioavailability, half life, and 4654 steady state to determine if a longer duration dog toxicity study is needed. 4655 11. Although the subchronic toxici ty testing guidelines include 4656 measurement of neurolog ical endpoints, such screens do not meet the 4657 requirement of the 90-day neurotoxicity study. For nonfood uses, if the 90-day 4658 study does not include a neurotoxicity scr een, then the acute neurotoxicity study 4659 will be required. 4660 12. Data are required if all of the following criteria are met: 4661 i. The intended use of the antimicrobial pesticide product is expected to 4662 result in repeated , dermal human exposure to the product , . 4663 ii. Data from a subchronic 90-day dermal toxicity st udy are not available , 4664

and

. 4665 iii. The 90-day dermal toxicity study has not been triggered. 4666*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

*** Deliberative Internal Document

– Do NOT Cite, Quote, or Release *** 13. EP testing is required if the product or any component of the product 4667 may increase dermal absorption of the acti ve ingredient(s) or increases its toxic 4668 or pharmacologic effects, as determined by testing using t he TGAI or based on 4669 available information about the toxic effects of the product or its components. 4670 14. Data are required if the active ingredient in the product is known or 4671 expected to be metabolized differently by the dermal route of exposure than by 4672 the oral route, and a metabo lite of the active ingredient is the toxic moiety. 4673 15. A 90-day oral toxicity test is not required for heating, ventilation, air 4674 conditioning, and refrigeration systems (co llectively referred to as HVAC&R). 4675 Instead , two 90-day toxicity tests, one by the dermal route and one by the 4676 inhalation route are required. 4677 16. Data are required if there is the likelihood of significant repeated 4678 inhalation exposure to the pestici de as a gas, vapor, or aerosol. 4679 17. Based on estimates of t he magnitude and dur ation of human 4680 exposure, studies of shorter duration, e. g., 21- or 28-days, may be sufficient to 4681 satisfy this requirement. The prim e consideration in determining the 4682 appropriateness of a shorter dur ation study is the likely period of time for which 4683 humans will be exposed. 4684 18. Based on the positive results of the acute or 90-day neurotoxicity 4685 studies, or on other data indicating neurot oxicity, a chronic neurotoxicity study 4686 (i.e

. .; a chronic study with additional neurotox icity evaluations) may be required to 4687 provide information about potential neurotox ic effects from long-term exposures. 4688*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

*** Deliberative Internal Document

– Do NOT Cite, Quote, or Release *** 19. Studies which are designed to si multaneously fulfil l the requirements 4689 of both the chronic oral and carcinogenicity studies (i .e., a combined study) may 4690 be conducted. 4691 20. For indirect food uses ≤ 200 ppb, and all other nonfood uses, data are 4692 required if either of the following criteria are met: 4693 i. The use of the pesticide is likely to result in repeated human exposure 4694 over a considerable portion of the human lifespan; or 4695 ii. The use requires that a tolerance, tolerance exemption, or food additive 4696 regulation or clearanc e be established. 4697 21. For indirect food uses ≤ 200 ppb, and all other nonfood uses, data are 4698 required if any of the fo llowing criteria , are met: 4699 i. The use of the pesticide is likely to result in significant human exposure 4700 over a considerable portion of the human life span which is significant in terms of 4701 frequency, time, duration, and/ or magnitude of exposure. 4702 ii. The use requires that a tolerance, tolerance exemption, or food additive 4703 regulation or clear ance be established. 4704 iii. The active ingredient, met abolite, degradate, or impurity: 4705 A. Is structurally relat ed to a recognized carcinogen; 4706 B. Causes mutagenic effects as demonstrated by in vitro or in vivo 4707 testing; or 4708 C. Produces a morphologic effect in any organ (e.g., hyperplasia, 4709 metaplasia) in subchronic studies t hat may lead to a neoplastic change. 4710*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

*** Deliberative Internal Document

– Do NOT Cite, Quote, or Release *** 22. If the requirement for a carc inogenicity study in any species is 4711 modified or waived for any reason, then a subchronic 90-day oral study in the 4712 same species may be required. 4713 23. Testing in two species is required for all uses. 4714 24. The oral route, by oral intubation, is preferred, unless the chemical or 4715 physical properties of the test substance, or the pattern of human exposure, 4716 suggest a more appropriate route of exposure. 4717 25. Additional testing by other ro utes of exposure may be required if the 4718 pesticide is determined to be a prenatal devel opmental toxicant after oral dosing. 4719 26. The developmental toxicity study in rodents may be combined with 4720 the two-generation reproduction study in rodents by using a second mating of the 4721 parental animals in either generation. Protocols must be approved by the 4722 Agency prior to the init iation of the study. 4723 27. A two-generation reproduc tion study is required. 4724 28. An information-based approach to testing is preferred, which utilizes 4725 the best available knowledge on the chem ical (hazard, pharmacokinetic, or 4726 mechanistic data) to determine whether a standard guideline study, an enhanced 4727 guideline study, or an alte rnative study should be c onducted to assess potential 4728 hazard to the developing animal. Applicants must submit any alternative 4729 proposed testing protocols and supporting sc ientific rationale to the Agency. 4730 Protocols must be approved by the Agency pr ior to the initiati on of the study. 4731 29. The use of a combined two- generation reproduction/developmental 4732 neurotoxicity study that utilizes the tw o-generation reproduction study in rodents 4733*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

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– Do NOT Cite, Quote, or Release *** as a basic protocol for the addition of other endpoints or functional assessments 4734 in the immature animal is encouraged. 4735 30. A DNT study is required usin g a weight-of-evidence approach when: 4736 i. The pesticide causes treatment -related neurological effects in adult 4737 animal studies (i.e, clinical signs of neurotoxicity, neuropathology, functional or 4738 behavioral effects). 4739 ii. The pesticide causes treatme nt-related neurological effects in 4740 developing animals, following pre- or postnatal post-natal exposure (i.e., nervous 4741 system malformations or neuropathy, brai n weight changes in offspring, 4742 functional or behavioral changes in the offspring). 4743 iii. The pesticide elicits a causat ive association between exposures and 4744 adverse neurological effects in human epidemiological studies. 4745 iv. The pesticide evokes a mechanism that is associated with adverse 4746 effects on the development of the nervous system (i.e ., structure-activity4747 relationship (SAR) to known neurotox icants, altered neu roreceptor or 4748 neurotransmitter responses). 4749 31. To facilitate the weight-of-ev idence determination for the pesticide’s 4750 mutagenicity, the Agency requires submission of other mutagenicity test results, 4751 besides those specifically listed in this table, that may have been performed. A 4752 reference list of all studies and papers known to the applicant concerning the 4753 mutagenicity of the test chemical must be submitted with the required studies. 4754 32. Due to the nature of antimicrobials, if testing with bacterial strains has 4755 not been conducted, then testing using a mammalian cell assay such as the 4756 mouse lymphoma TK +/- assay is preferred. If reverse mutation assay testing 4757*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

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– Do NOT Cite, Quote, or Release *** with bacterial strains has already been c onducted, and the test ing was conducted 4758 at levels that did not cause toxicity to the bacterial stra ins tested, then the 4759 applicant may submit the study to fulfill this data requirement. 4760 33. For the in vitro mammalian gene mutation study, there is a choice of 4761 assays using either mouse lymphoma L5178 Y cell thymidine kinase (tk) gene 4762 locus, maximizing assay conditions for small colony expression and detection; 4763 Chinese hamster ovary (CHO ) or Chinese hamster lung fibroblast (v79) cells, 4764 hypoxanthine-guanine phos phoribosyl transferase (hgprt) gene locus, 4765 accompanied by an appropriate in vitro test for clastogenicity; or CHO cells 4766 strains AS52, xanthine-guani ne phosphoribosyl transferase (xprt) gene locus. 4767 34. There is a choice of assa ys, but the micronuc leus rodent bone 4768 marrow assay is preferred; the ro dent bone marrow assays using metaphase 4769 analysis (aberrations) are acceptable. 4770 35. Data are required when chronic to xicity or carcinogenicity studies are 4771 also required. 4772 36. Data is required if the produc t label directs that it be applied to 4773 domestic animals, such as cats, dogs, cattle, pigs, and horses. 4774 37. In the absence of dermal absor ption data or a repeated dose dermal 4775 toxicity study, the assumption of 100% de rmal absorption would be used in a risk 4776 assessment to determine if a dermal penetrati on study is required, and to identify 4777 the doses and duration of exposure for which dermal absorption is to be 4778 quantified. 4779 38. Required for nonfood uses, if oral exposure could occur. 4780*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

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– Do NOT Cite, Quote, or Release *** 39. Data may be required if si gnificant adverse effects are 4781 seen in available toxicology studies and these effects can be 4782 further elucidated by metabolism and pharmacokinetics studies. 4783 § 158.2240 Nontarget organisms. 4784 (a) General . Subpart B of this part and § 158.2201 describe how to use 4785 the table in paragraph (c) of this secti on to determine the terrestrial and aquatic 4786 nontarget organisms data requi rements for a particular antimicrobial pesticide 4787 product. Notes that apply to an individual test , including specific conditions, 4788 qualifications, or excepti ons are listed in paragraph (d) of this section. 4789 (1) Terrestrial and aquatic nontar get organism data are required to 4790 support the registration of most end-us e and manufacturing-use antimicrobial 4791 products. 4792 (2) Data are generally not required to support end-use products of a gas, 4793 highly volatile liquid, highly reactive so lid, or a highly corrosive material. 4794 (3) Data on transformation/degradation products or leachate residues of 4795 the parent compound are al so required to support registration, if the 4796 transformation/degradation/leachate products meet one of the following criteria: 4797 (i) More toxic, persistent, or bioaccumulative than the parent; 4798 (ii) Have been shown to cause adver se effects in mammalian or aquatic 4799 reproductive studies; or 4800 (iii) The moiety of concern (i.e., functional group in the parent chemical 4801 molecule that imparts adverse effects) remains intact. 4802 (4) If an antimicrobial may be applied to a field crop, horticultural crop, or 4803 turf, then the data require ments in §158.630 apply. 4804*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

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– Do NOT Cite, Quote, or Release *** (5) For the purpose of determining dat a requirements, the all other use 4805 patterns category includes t he following use patterns: 4806 (i) Agricultural premises and equipment. 4807 (ii) Food-handling/stor age establishments, premises, and equipment. 4808 (iii) Commercial, institutional a nd industrial premises and equipment. 4809 (iv) Residential and public access premises. 4810 (v) Medical premises and equipment. 4811 (vi) Human drinking water systems. 4812 (vii) Materials preservatives. 4813 (viii) Swimming pools. 4814 (b) Key. MP = Manufacturing use product; EP = End-use product; R = 4815 Required; CR = Condit ionally required; NR = Not required; TGAI = Technical 4816 grade of the active ingredient; TEP = Typical end-use product; PAIRA = Pure 4817 active ingredient radiolabeled ; a.i. = active ingredient. 4818 4819(c)Antimicrobial nontarget organism data requirementstable.The following table shows the data4820requirements for nontarget organisms. The test notes appear inparagraph (d) of this section.4821Table -- Antimicrobial Nontarget Organism DataRequirements4822GuidelineNumberData Requirement Use Pattern Test Substance TestNoteNo.IndustrialProcesses andWater SystemsAntifoulantCoatings andPaintsWoodPreservativesAquaticAreasAll OtherUsePatternsCategoryMP EPTier One Testing850.2100 Acute avian oraltoxicityR R R R R TGAI TGAI 1850.1010 Acute freshwaterinvertebratestoxicityR R R R R TGAI TGAI 2850.1075 Acute freshwaterfish toxicityR R R R R TGAI TGAI 3Higher Tier TestingAvian Testing850.2200 Avian dietarytoxicityCR CR CR CR CR TGAI TGAI 4850.2300 Avian reproduction CR CRCR CR CR TGAI TGAI 1, 6Aquatic Organisms Testing850.1010 Acute freshwaterinvertebratestoxicityCR CR CR CR CR --- TEP 2, 5, 7850.1075 Acute freshwaterfish toxicityCRCR CR CR CR --- TEP 3, 5, 7850.1025850.1035850.1045850.1055850.1075Acute estuarineand marineorganisms toxicityCR R CR CR CR TGAI TGAI 8, 9Acute estuarineand marineorganisms toxicityCR CR CR CR CR --- TEP 5, 7, 8850.1400 Fish early-life stage RR R R R TGAI TGAI 10850.1300850.1350Aquaticinvertebrate lifeRR R R R TGAI TGAI 10*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ****** Deliberative Internal Document–Do NOT Cite, Quote, or Release ***GuidelineNumberData Requirement Use Pattern Test Substance TestNoteNo.IndustrialProcesses andWater SystemsAntifoulantCoatings andPaintsWoodPreservativesAquaticAreasAll OtherUsePatternsCategoryMP EPcycle850.1500 Fish life-cycle CR CRCR CR CR TGAI TGAI 11, 12850.1710850.1730850.1850Aquatic organisms,bioavailability,biomagnification,toxicity testsCR CR CR CR CR TGAI.PAI,degradateTGAI.PAI,degradate13850.1950 Simulated or actualfield testing foraquatic organismsCR CR CR CR CR TEP TEP 14, 15,16Sediment Testing850.1735 Whole sediment;acute freshwaterinvertebratesCR CR CR CR CR TGAI TGAI 15, 17850.1740 Whole sediment;acute marineinvertebratesCR CR CR CR CR TGAI TGAI 15, 17,19None Whole sediment;chronicinvertebrates freshwater and marineCR CR CR CR CR TGAI TGAI 15, 18,19Insect Pollinator Testing850.3020 Honeybee acutecontactNR NR R NR CR TGAI TGAI 20850.3030 Toxicity of residuesto honeybeesNR NR R NR CR TGAI TEP ortreatedwood20, 214823*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

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– Do NOT Cite, Quote, or Release *** (d) Test notes . The following test notes appl y to the data requirements in 4824 the table to paragraph (c) of this section: 4825 1. For industrial processes and water systems, antifoulant paints and 4826 coatings, wood preservatives, and aquatic areas, data are required for two avian 4827 species: one waterfowl species and one upl and game bird species. For the all 4828 other use patterns category (as specifi ed in § 158.2240(a)(5)), data are required 4829 for one avian species. 4830 2. Data are required on one freshw ater aquatic invertebrate species. 4831 3. For the industrial processes and water systems, antifoulant paints and 4832 coatings, wood preservatives, and aquatic use pattern areas, data are required 4833 on two species of fish, one coldwater species and one warmwater species. For 4834 the “ All Other” use patterns category (as sp ecified in § 158.2240(a)(5)), data are 4835 required on one two species of fish, either one coldwater species or a and one 4836 warmwater species. Testing on a second species is required if the active 4837 ingredient or principal tr ansformation products are st able in the environment and 4838 the LC 50 in the first species is greater less than or equal to 1 ppm or 1 mg/L. 4839 4. Data are required on one avian s pecies, either one waterfowl species 4840 or one upland game bird species, if the avian acute oral LD 50 ( TGAI testing) is 4841 less than or equal to 100 mg. a.i./kg and a.i. residues or its principal 4842 transformation products are likely to occur in avian feed items. Data on the 4843 second species are required if the avian dietary LC 50 in the first species tested is 4844 less than or equal to 500 ppm a.i. in the diet. 4845*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

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– Do NOT Cite, Quote, or Release *** 5. If TEP testing cannot be conduct ed due to the physical characteristics 4846 of the test substance (for example, a paint), then t he applicant should request a 4847 waiver. 4848 6. Data are required if one or mo re of the following criteria are met: 4849 i. Birds may be subjected to r epeated or continued exposure to the 4850 pesticide or any of its transformation produc ts, especially preceding or during the 4851 breeding season. 4852 ii. The pesticide or any of its ma jor metabolites or degradation products 4853 are stable in the environment to the ext ent that a potentially toxic amount may 4854 persist in avian feed. 4855 iii. The pesticide or any of its ma jor metabolites or degradation products 4856 are stored or accumulated in plant or animal tissues, as indicated by the 4857 octanol/water partition coefficient (K ow is greater than or equal to 1,000), 4858 accumulation studies, metabolic release and retention studies, or as indicated by 4859 structural similarity to know n bioaccumulative chemicals. 4860 iv. Any other information, such as that derived from mammalian 4861 reproduction studies, indicates that repr oduction in terrestrial vertebrates may be 4862 adversely affected by the anticipat ed use of the pesticide product. 4863 7. TEP testing is required for any product which meets one or more of the 4864 following conditions: 4865 i. When based on deterministic m odeling results: If the Estimated 4866 Environmental Concentration (EEC) in the aquatic environment is equal to or 4867 greater than one-half the LC 50 /EC 50 of the TGAI. 4868*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

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– Do NOT Cite, Quote, or Release *** ii. When based on probabilistic modelin g results: If the estimated 10 th 4869 percentile 7Q10 Surface Water Concentrati on exceeds the acute concentration 4870 of concern (i.e., one-half the LC 50 /EC 50 ) for 4 or more days. ). 4871 iii. If an ingredient in the end-use pr oduct other than the active ingredient 4872 is expected to enhance the toxicity of the ac tive ingredient or to cause toxicity to 4873 aquatic organisms. 4874 iv. The end-use antimicrobial pr oduct will be applied directly into an 4875 aquatic environment. 4876 8. Data are required on one es tuarine/marine mollusk, one other 4877 estuarine/marine invertebrate, and one estuarine/marine fish species. 4878 9. For the all other use pa tterns category (as specified in § 4879 158.2240(a)(5)), industrial processes and water systems, wood preservatives, 4880 and aquatic areas, data are required if t he pesticide residues from the parent 4881 compound and/or transformation products are likely to enter the estuarine/marine 4882 environment. 4883 10. Testing must be conducted with the most sensitive organism (either 4884 freshwater or estuarine/ma rine vertebrates, or freshwat er or estuarine/marine 4885 invertebrates), as determined from the resu lts of the acute toxicity tests (acute 4886 EC 50 freshwater invertebrates; acute LC 50 /EC 50 estuarine and marine organisms; 4887 acute freshwater fish LC 50 ). 4888 11. Data are required on estuarine/ marine species if the product is 4889 intended for direct application to the es tuarine or marine environment, or the 4890 product is expected to enter this envir onment in significant concentrations 4891 because of its expected use or mobility patterns. 4892*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

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– Do NOT Cite, Quote, or Release *** 12. Data are required on freshwat er species if the end-use product is 4893 intended to be applied directly to water, or is expected to be transported to water 4894 from the intended use site, and when one or more of the following conditions 4895 apply: 4896 i. When based on deterministic m odeling results: If the Estimated 4897 Environmental Concentration (EEC) in wate r is equal to or greater than 0.1 of the 4898 no-observed-adverse-effect concentration or no-observed-adverse-effect level 4899 (NOAEC/NOAEL) in the fish early-life stage or invertebrate life cycle tests. 4900 ii. When based on probabilistic modelin g results: If the estimated 10 th 4901 percentile 7Q10 Surface Water Concentra tion based on probabilistic modeling 4902 exceeds for 20 days or more the chronic concentration of concern (i.e., one-tenth 4903 the NOAEC or NOAEL) determined in the fish early-life stage or invertebrate life 4904 cycle tests. 4905 iii. If studies of other organisms indi cate that the reproductive physiology 4906 of fish may be affected. 4907 13. Not required when: 4908 i. The octanol/water partition coeffi cients of the pesticide and its major 4909 degradates are less than 1,000; 4910 ii. There are no potential exposures to fish and other nontarget aquatic 4911 organisms; or 4912 iii. The hydrolytic half-life is less than 5 days at pH 5, 7, and 9. 4913 14. Environmental chemistry me thods used to generate data associated 4914 with this study must include results of a successful confirmato ry method trial by 4915 an independent laboratory. Test standards and procedures for independent 4916*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

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– Do NOT Cite, Quote, or Release *** laboratory validation are available as addenda to the guideline for this test 4917 requirement. 4918 15. Protocols must be approved by the Agency prior to the initiation of the 4919 study. 4920 16. Data are required if the intended use pattern, and the 4921 physical/chemical properti es and environmental fate characteristics of the 4922 antimicrobial indicate significant potent ial exposure, and, based on the results of 4923 the acute and chronic aquatic organism testing, significant impairment of 4924 nontarget aquatic organism s could result. 4925 17. Data are required if the half-life of the pesticide in the sediment is 4926 equal to or less than 10 days in either the aerobic soil or aquatic metabolism 4927 studies, and if one or more of the following conditions are met: 4928 i. The soil partition coefficient (K d ) is equal to or greater than 50 L/kg. 4929 ii. The log K ow is equal to or greater than 3. 4930 iii. The K oc is equal to or greater than 1,000. 4931 18. Data are required if the EEC in sediment is greater than 0.1 of the 4932 acute LC 50/ EC 50 values and if one or more of t he following conditions are met: 4933 i. The soil partition coefficient (K d ) is equal to or greater than 50 L/kg. 4934 ii. The log K ow is equal to or greater than 3. 4935 iii. The K oc is equal to or greater than 1,000. 4936 19. Sediment testing wit h estuarine/marine test species is required if the 4937 product is intended for direct application to the estuarine or marine environment 4938 or the product is expected to enter this environment in significant concentrations 4939 either by runoff or erosion, because of its expected use or mobility pattern. 4940*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

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– Do NOT Cite, Quote, or Release *** 20. For the all other use patte rns category (as specified in § 4941 158.2240(a)(5)), data are r equired only for beehive applications when the 4942 beehive (empty or occupied) may be treated. 4943 21. A study similar to “Honey Bee Toxicity of Residues on Foliage” is 4944 required using treated wood in stead of the foliage. Pr otocols must be approved 4945 by the Agency prior to the in itiation of the study. 4946 §158.2250 Nontarget plant protection. 4947 (a) Subpart B of this part and § 158. 2201 describe how to use the table in 4948 paragraph (f) of this sect ion to determine the nontarget plant protection data 4949 requirements for a particular antimicrobial pesticide product. Notes that apply to 4950 an individual test including specific condi tions, qualifications, or exceptions are 4951 listed in paragraph (g) of this section. 4952 (b) Data on transformation/degradation products or leachate residues of 4953 the parent compound are al so required to support registration, if the 4954 transformation/degradation/leachate products meet one of the following criteria: 4955 ( i 1 ) More toxic, persistent, or bioaccumulative than the parent; 4956 ( ii 2 ) Have been shown to cause adverse effects in mammalian or aquatic 4957 reproductive studies; or 4958 (1) (iii) The moiety of concern (i.e., functional group in the parent 4959 chemical molecule that imparts adverse effects) remains intact. 4960 (3) The moiety of concern (i.e., functional group in the parent chemical 4961 molecule that imparts adverse effects) remains intact. 4962 (c) For the purpose of determining dat a requirements, the all other use 4963 patterns category includes t he following use patterns: 4964 ( i 1 ) Agricultural premises and equipment. 4965*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

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– Do NOT Cite, Quote, or Release *** ( ii 2 ) Food-handling/storage establishm ents, premises, and equipment. 4966 ( iii 3 ) Commercial, institutional an d industrial premises and equipment. 4967 ( iv 4 ) Residential and public access premises. 4968 ( v 5 ) Medical premises and equipment. 4969 ( vi 6 ) Human drinking water systems. 4970 ( vii 7 ) Materials preservatives. 4971 ( viii 8 ) Swimming pools. 4972 (d) If an antimicrobial may be applied to a field crop, horticultural crop, or 4973 turf, then the data requirem ents in 40 CFR 158.660 apply. 4974 (e) Key. MP = Manufacturing use pr oduct; EP = End-use product; R = 4975 Required; CR = Condit ionally required; NR = Not required; TGAI = Technical 4976 grade of the active ingredient; TEP = Typical end-use product. 4977*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ****** Deliberative Internal Document–Do NOT Cite, Quote, or Release ***(f)Nontarget plant protection data requirementstable.The following table shows the data requirements for4978nontarget plant protection. The test notesappear in paragraph (g) of this section.4979Table -- Nontarget Plant Protection Data Requirements4980GuidelineNumberData Requirement Use Pattern Test Substance TestNoteNo.IndustrialProcesses andWater SystemAntifoulantCoatings andPaintsWoodPreservativesAquaticAreasAll OtherUsePatternsCategoryMP EP850.4225 Seedlingemergence, Tier II– dose responseCR 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) TierII – dose responseR R R R CR TGAI,TEPTGAI,TEP4, 10850.5400Aquatic plantgrowth (algal) TierII (dose response)R R R R RTGAI,TEPTGAI,TEP4, 5, 6850.4300 Terrestrial field CRCRCRCRCRTEP TEP 7, 8, 9850.4450 Aquatic field CRCRCRCRCRTEP TEP 7, 8, 94981(g) Test notes. The following test notes apply to the data requirements in 4982 the table to paragraph (f) of this section: 4983 1. Data on only one plant species (rice, Oryza sativa ) are required. 4984 2. Data are required if the risk quoti ent from any aquatic plant growth Tier 4985 II study exceeds a level of concern for aquatic plants. 4986 3. Not required when: 4987 i. There are no potential exposures to plants; 4988 ii. The hydrolytic half-life is le ss than 5 days at pH 5, 7, and 9; or 4989 iii. The results of a biodegradation study indicate that the active ingredient 4990 or principal degradation pr oducts are not biodegradable in 28 days, i.e. the 4991 biodegradation curve has not reached a plat eau for at least three determinations 4992 within the 28 days. 4993 4. For TEP testing, data are re quired for the applicant’s end-use product 4994 if an ingredient in the end-use product, other than the active ingredient, is 4995 expected to enhance the toxicity of the active ingredient. 4996 5. One Tier II (dose re sponse) study, conducted with Selenastrum 4997 capricornutum, is required for the all other use patterns category (as specified in 4998 § 158.2250(c)). If the results of this study exhibit detrim ental effects (EC 50 less 4999 than 1.0 ppm or mg/L), then additional Tier II (dose response) studies are 5000 required on three species ( Anabaena flos-aquae, Navicula pelliculosa, and 5001 Skeletonema costatum). 5002 6. For industrial processes and wa ter systems, antifoulant coatings and 5003 paints, wood preservatives, and aquatic ar eas, Tier II (dose response) studies 5004*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

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– Do NOT Cite, Quote, or Release *** are required on four species ( Anabaena flos-aquae, Navicula pelliculosa, 5005 Skeletonema costatum, and Selenastrum capricornutum ). 5006 7. Environmental chemistry methods used to generate data must include 5007 the results of a successful confirma tory method trial by an independent 5008 laboratory. 5009 8. Tests are required on a case-by-case basis based on the results of 5010 lower tier plant protection studies, adver se incident reports, intended use pattern, 5011 and environmental fate characteristi cs that indicate potential exposure. 5012 9. Protocols must be approved by the Agency prior to the initiation of the 5013 study. 5014 10. For the all other use patterns cat egory (as specified in § 158.2250(c)), 5015 data are required if the aquatic (algal) pl ant growth Tier II study demonstrates 5016 detrimental effects at le ss than 1.0 ppm or mg/L. 5017 §158.2260 Applicator exposure. 5018 (a) General. Subpart B of this part and § 158.2201 describe how to use 5019 the table in paragraph (d) of this sect ion to determine the applicator exposure 5020 data requirements for antimic robial pesticide products. Notes that apply to an 5021 individual test including specific condition s, qualifications, or exceptions are listed 5022 in paragraph (e) of this section. 5023 (1) The Agency may accept surrogat e exposure data estimations and/or 5024 modeling estimations from other sources to satisfy exposure data requirements. 5025 The surrogate data must meet the basic quality assuranc e, quality control, good 5026 laboratory practice, and other scientif ic requirements set by EPA. To be 5027 acceptable, the Agency must find that the surrogate exposure data estimations 5028*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

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– Do NOT Cite, Quote, or Release *** have adequate information to address the applicable exposure data requirements 5029 and contain adequate monitoring events of acceptable qualit y. The data must 5030 reflect the specific use prescribed on t he label and the activity of concern, 5031 including formulation type, application me thods and rates, type of activity, and 5032 other pertinent information. 5033 (2) Occupational uses include no t only handlers, mixers, loaders, and 5034 applicators, but also commercial applications to residential sites. Residential 5035 uses are limited to non-occupational, i.e., non-professional, antimicrobial 5036 applications. Both occupational and resi dential applicator data may be required 5037 for the same product. 5038 (b) Criteria for testing . Applicator exposure data described in the table to 5039 paragraph (d) of this section are required based on toxicity and exposure criteria. 5040 Data are required if at leas t one of the toxicity criteria in paragraph (b)(1) of this 5041 section, and at least one of the exposur e criteria in paragr aph (b)(2) of this 5042 section are met. 5043 (1) Toxicity criteria. (i) Evidence of potentially significant adverse effects 5044 have been observed in any applicable toxicity studies. 5045 (ii) Scientifically s ound epidemiological or poi soning incident data with a 5046 clear cause-effect relationship indicati ng that adverse health effects may have 5047 resulted from exposure to the pesticide. 5048 (2) Exposure criteria. --(i) Dermal exposure may occur during product 5049

use. 5050 (ii) Respiratory exposure ma y occur during product use. 5051*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

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– Do NOT Cite, Quote, or Release *** (c) Key. R = Required; CR = Conditionally required; TEP = Typical end5052 use product. 5053 (d) Antimicrobial applicator exposure data requirements table. The 5054 following table shows the data requirement s for applicator exposure. The test 5055 notes appear in paragraph (e ) of this section. 5056 Table -- Antimicrobial Applic ator Exposure Data Requirements 5057 Guideline Number Data Requirements Use Sites Test Substance Test Note No. Occupational Residential
875.1100 875.1200 Dermal exposure R R TEP 1, 2, 3, 4 875.1300 875.1400 Inhalation exposure R R TEP 1, 2, 3, 4 875.1500 Biological monitoring CR CR TEP 1, 2, 3 875.1600 Data reporting and calculations R R TEP 5 875.1700 Product use information R R TEP -- 5058 (e) Test notes. The following test notes appl y to the data requirements in 5059 the table to paragraph (d) of this section: 5060 1. Prior to initiation of the study, pr otocols involving intentional exposure 5061 of human subjects must be submitted for review by EPA and then the Human 5062 Studies Review Board (HSRB) accordi ng to 40 CFR 26.1125. Examples of 5063 proposed human study research can be found in various reviews provided by the 5064 Human Studies Review Board ( http://www.epa.gov/osa/hsrb/index.htm ). 5065 2. Biological monitoring data may be s ubmitted in addition to, or in lieu of, 5066 dermal and inhalation passive dosimetr y exposure data, provided the human 5067 pharmacokinetics of the pesticide or metabolite/analog compounds ( i.e. , 5068 whichever method is selected as an indicator of body burden or internal dose) 5069 allow for the back calculation to the total internal dose. 5070*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

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– Do NOT Cite, Quote, or Release *** 3. For products with both indoor and outdoor uses, and similar conditions 5071 of use, data are generally required for t he indoor applications only. However, 5072 data for outdoor uses are required if the A gency expects outdoor uses to result in 5073 greater exposure than indoor uses (e .g., higher use rates and application 5074 frequency, or longer exposure duration, or applicati on methods/equipment create 5075 potential for increased dermal or inhalat ion exposure in outdoor versus indoor 5076 use sites). In certain cases, when a pesticide may be used both indoors and 5077 outdoors under dissimilar conditions of us e, the Agency may require submission 5078 of applicator exposure data for both use patterns. 5079 4. EPA will consider waiving this data requirement for antimicrobials 5080 applied via closed loading syst ems if the antimicrobial has a low vapor pressure. 5081 5. Data reporting and calculations are required only if handler exposure 5082 data are required. 5083
§158.2270 Post-application exposure

. 5084 (a) General. Subpart B of this part and § 158.2201 describe how to use 5085 the table in paragraph (d) of this se ction to determine the post-application 5086 exposure data requirements for anti microbial pesticide products. The data 5087 generated during these studies are used to determine the quantity of pesticide to 5088 which people may be exposed after applicati on. Notes that apply to an individual 5089 test, including specific conditions, qualific ations, or exceptions to the designated 5090 test, are listed in paragr aph (e) of this section. 5091 (1) Post-application exposure data are required when certain toxicity 5092 criteria are met and the human activiti es associated with the pesticide's use 5093 pattern can lead to potential adverse exposures. 5094*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

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– Do NOT Cite, Quote, or Release *** (2) The Agency may accept surrogat e exposure data estimations and/or 5095 modeling estimations from other sources to satisfy exposure data requirements. 5096 The surrogate data must meet the basic quality assuranc e, quality control, good 5097 laboratory practice, and other scientif ic requirements set by EPA. To be 5098 acceptable, the Agency must find that the surrogate exposure data estimations 5099 have adequate information to address the applicable exposure data requirements 5100 and contain adequate monitoring events of acceptable qualit y. The data must 5101 reflect the specific use prescribed on t he label and the activity of concern, 5102 including formulation type, application me thods and rates, type of activity, and 5103 other pertinent information. 5104 (b) Criteria for testing. Post-application exposu re data described in the 5105 table to paragraph (d) of this section are required based on toxicity and exposure 5106 criteria. Data are required if at least one of the toxicity criteria in paragraph (b)(1) 5107 of this section, and at least one of the ex posure criteria in par agraph (b)(2) of this 5108 section are met. 5109 (1) Toxicity criteria. --(i) Evidence of potentially significant adverse effects 5110 have been observed in any applicable toxicity studies. 5111 (ii) Scientifically s ound epidemiological or poi soning incident data with a 5112 clear cause-effect relationship indicati ng that adverse health effects may have 5113 resulted from exposure to the pesticide. 5114 (2) Exposure criteria. --(i) Outdoor uses. (A) Occupational human post5115 application or bystander exposure to resi dues of antimicrobial pesticides could 5116 occur as the result of, but is not limited to , worker re-entry in to treatment sites, 5117*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

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– Do NOT Cite, Quote, or Release *** clean-up and equipment maintenance tasks, handling wood preservative-treated 5118 wood, or other work-related activity. 5119 (B) Residential human post-applicati on or bystander exposure to residues 5120 of antimicrobial pesticides could occur following the applicat ion of antimicrobial s 5121 pesticides to outdoor areas and spaces at residential sites, such as, but not 5122 limited to homes, daycare center s, and other public buildings. 5123 (ii) Indoor uses. (A) Occupational human po st-application or bystander 5124 exposure to pesticide re sidues could occur followin g the application of the 5125 antimicrobial pesticide to indoor spaces or surfaces. 5126 (B) Residential human post-applic ation or bystander exposure to 5127 pesticide residues could occur following the application of the antimicrobial 5128 pesticide to indoor spaces or surfaces at residential sites, such as, but not limited 5129 to homes, daycare centers, hospitals , schools, and other public buildings. 5130 (c) Key. R = Required; CR = Conditionally required; NR = Not required; 5131 TEP = Typical end-use product. 5132 (d) Antimicrobial post-application exposure data requirements table. The 5133 following table shows the data requirement s for post-application exposure. The 5134 test notes appear in paragraph (e) of this section. 5135 Table -- Antimicrobial Post-App lication Exposure Data Requ irements. 5136 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 ---*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

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– Do NOT Cite, Quote, or Release *** 875.2800 Description of human activity R R TEP --- 875.2900 Data reporting and calculations R R TEP 10 5137 (e) Test notes. The following test notes appl y to the data requirements in 5138 the table to paragraph (d) of this section: 5139 1. Prior to initiation of the study, pr otocols involving intentional exposure 5140 of human subjects must be submitted for review by EPA and then the Human 5141 Studies Review Board (HSRB) accordi ng to 40 CFR 26.1125. Examples of 5142 proposed human study research can be found in various reviews provided by the 5143 Human Studies Review Board (HSRB) ( http://www.epa.gov/osa/hsrb/index.htm). 5144 2. For residential wood preservative uses, data may be required if soil has 5145 the potential to be an import ant exposure pathway, and so il is in contact with or 5146 adjacent to treated wood, in cluding but not limited to decks, play sets, and 5147 gazebos, 5148 3. Protocols must be appr oved by the Agency prior to the initiati on of the 5149 study. 5150 4. For wood preservatives, data ar e required for treated wood surfaces 5151 where post-application contact with treated wood is anticipated. 5152 5. For occupational uses, data ar e required if the pesticide may be 5153 applied to or around surfaces, and if the hu man activity data indicate that workers 5154 are likely to have post-application derma l contact with treated surfaces while 5155 participating in typical activities. 5156 6. Data are required for residential use sites, schools, and daycare 5157 institutions. This includes but is not limited to the follo wing: Residential and 5158 public access premises; material pres ervatives (including those used in 5159*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

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– Do NOT Cite, Quote, or Release *** residential products, including but not lim ited to clothing and plastic toys) and 5160 wood preservatives (when contact with treated wood is likely to occur). 5161 7. Data are required for occupati onal and residential uses if the human 5162 activity data indicate the potential for post-application dermal and/or inhalation 5163 exposures while participating in typica l activities and no acceptable modeling 5164 options are available. 5165 8. Biological monitoring data may be subm itted in addition to, or in lieu of, 5166 dermal and inhalation passive dosime try exposure data provided the human 5167 pharmacokinetics of the pesticide or metabolite/analog compounds ( i.e. , 5168 whichever method is selected as an indicator of body burden or internal dose) 5169 allow for a back-calculation to the total internal dose. 5170 9. Data are required for occupational and residential uses if there is the 5171 potential for bystander exposure and the pesti cide use could result in respirable 5172 and/or inhalable material (e.g., gas, vapor, aerosol, or particulates). 5173 10. Data reporting and calculations are required only if post-application 5174 exposure data are required. 5175 §158.2280 Environmental fate. 5176 (a) General. Subpart B of this part and § 158.2201 describe how to use 5177 the table in paragraph (c) of this secti on to determine the environmental fate data 5178 requirements for antimicrobial pestici de products. Notes that apply to an 5179 individual test including specific condition s, qualifications, or exceptions are listed 5180 in paragraph (d) of this section. 5181 (1) Environmental fate data are requir ed to support the registrations of all 5182 end-use and manufacturing-use antimicrobial products. 5183*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

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– Do NOT Cite, Quote, or Release *** (2) Data on transformation/degradation products or leachate residues of 5184 the parent compound are al so required to support registration, if the 5185 transformation/degradation/leachate products meet one of the following criteria: 5186 (i) More toxic, persistent, or bioaccumulative than the parent; 5187 (ii) Have been shown to cause adver se effects in mammalian or aquatic 5188 reproductive studies; or 5189 (iii) The moiety of concern (i.e., functional group in the parent chemical 5190 molecule that imparts adverse effects) remains intact. 5191 (3) For the purpose of dete rmining data requirements, the “A ll O ther ” all 5192 other use patterns category includes the following use patterns: 5193 (i) Agricultural premises and equipment. 5194 (ii) Food-handling/stor age establishments, premises, and equipment. 5195 (iii) Commercial, institutional a nd industrial premises and equipment. 5196 (iv) Residential and public access premises. 5197 (v) Medical premises and equipment. 5198 (vi) Human drinking water systems. 5199 (vii) Materials preservatives. 5200 (viii) Swimming pools. 5201 (b) Key

. MP = Manufacturing use product; EP = End-use product; R = 5202 Required; CR = Condit ionally required; NR = Not required; TGAI = Technical 5203 grade of the active ingredient; TEP = Typical end-use product; PAIRA = Pure 5204 active ingredient radiolabeled; ROC = residue of concern. 5205(c)Antimicrobial environmentalfate data requirementstable.The following table shows the data requirements for5206environmental fate. The test notes appearin paragraph (d) of this section.5207Table -- Antimicrobial Environmental Fate Data Requirements5208GuidelineNumberData Requirement Use Pattern Test Substance TestNoteNo.IndustrialProcesses andWater SystemsAntifoulantCoatings andPaintsWoodPreservativesAquaticAreasAll OtherUsePatternsCategoryMP EPDegradation Studies – Laboratory835.2120 Hydrolysis R R R R R TGAI orPAIRATGAI orPAIRA1835.2240 Photodegradationin waterR R R R R TGAI orPAIRATGAI orPAIRA2835.2410 Photodegradationin soilNR NR R NR NR TGAI orPAIRATGAI orPAIRA10Toxicity and Fate in Wastewater Systems850.6800OECD 209Activated Sludge,RespirationInhibition TestR R R NR R TGAI TGAI835.1110 Activated SludgeSorption IsothermCR CR CR NR CR TGAI TGAI 19, 20835.3110 ReadyBiodegradabilityCR CR CR NR CR TGAI TGAI 3, 4,18835.3220 Porous Pot Study CR CRCR NR CR TGAI TGAI 3, 18835.3280 Simulation Teststo Assess theBiodegradability ofChemicalsDischarged inWastewaterCR CR CR NR CR TGAI TGAI 3, 18835.3240 Simulation Test –Aerobic SewageTreatment: A.Activated SludgeUnitsCR CR CR NR CR TGAI TGAI 3, 18*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ****** Deliberative Internal Document–Do NOT Cite, Quote, or Release ***Mobility 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, 8835.4300 Aerobic aquaticmetabolismR R R R CR TGAI orPAIRATGAI orPAIRA5, 8835.4400 Anaerobic aquaticmetabolismR R R R CR TGAI orPAIRATGAI orPAIRA5, 8Dissipation Studies – Field835.6200 Aquatic (sediment) CR R CR R CR TEP TEP 11, 12,13Ground and Surface Water MonitoringNone Monitoring ofrepresentativeU.S. watersCR CR CR CR CR ROC ROC 11, 14,17Special StudiesNone Special leaching NR R R NR NR TGAI TEP 15, 16*** EO 12866 Draft – Do Not Cite, Quote or Release During Review *** (d) Test notes. The following test notes appl y to the data requirements in 5209 the table in paragraph (c) of this section: 5210 1. For testing antifoulant paints and coatings, testing is to be performed 5211 separately with both sterile bu ffered distilled water and st erile synthetic seawater 5212 at pHs 5, 7, and 9. 5213 2. Not required if: 5214 ( i )

. The electronic absorption spectra, measured at pHs 5, 7 and 9, of the 5215 chemical and its hydrolytic products, if any, show no absorption or tailing 5216 between 290 and 800 nm, inclusive; or 5217 ( ii )

. The results of the hydrolysis st udy at all three pHs (5, 7, and 9) 5218 demonstrates a half-life of less than 30 days. 5219 3. The results of the activated sl udge, respiration inhibition (ASRI) test 5220 determine which of the following tests are required: R eady biodegradability, 5221 porous pot, the biodegradation in activa ted sludge study as described in the 5222 “Simulation Tests to Assess the Biodegr adability of Chemicals Discharged in 5223 Wastewater,” or simulation test – aerobi c sewage treatment: A. activated sludge 5224 units. 5225 ( i ).

. If the ASRI test EC 50 is equal to or less than 20 mg/L, then the 5226 applicant must choose either to: 5227 ( A ).

. Conduct the biodegradation in activated sludge study as described in 5228 the “Simulation Tests to Assess the Bi odegradability of Chemicals Discharged in 5229 Wastewater”; 5230 ( B ).

. Conduct the porous pot test; or 5231*** EO 12866 Draft – Do Not Cite, Quote or Release During Review *** ( C )

. . Conduct the simulation test – aerobi c sewage treatment: A. activated 5232 sludge units. 5233 ( ii ).

. If the ASRI test EC 50 is greater than 20 mg/L, then the applicant must 5234 choose either to: 5235 ( A ).

. Conduct a ready biodegr adability study; or 5236 ( B ).

. Conduct one of the following st udies: The biodegradation in 5237 activated sludge study as described in the “Simulation Tests to Assess the 5238 Biodegradability of Chemical s Discharged in Wastewater,” the porous pot test, or 5239 the simulation test – aerobic sewage treat ment: A. activated sludge units. 5240 4. Pass criteria for the ready bi odegradability study are: 70% removal of 5241 dissolved organic carbon (DOC) and 60% re moval of theoretical oxygen demand 5242 (ThOD) or theoretical carbon dioxide (ThCO 2 ) production for respirometric 5243 methods. These pass levels must be r eached in a 10-day window within the 28- 5244 day period of the test. If the antimicrobial passes the ready biodegradability 5245 study, then no further testing is required. If the antimicrobial fails the ready 5246 biodegradability study, t hen the applicant must c onduct one of the following 5247 studies: The biodegradation in activa ted sludge study as described in the 5248 “Simulation Tests to Assess the Biodegr adability of Chemicals Discharged in 5249 Wastewater,” the porous pot test, or the simulation test – aerobic sewage 5250 treatment: A. activat ed sludge units. 5251 5. For the all other use patte rns category (as specified in § 5252 158.2280(a)(3)), data are requi red based on a weight-of- evidence evaluation of 5253 the results of the hydrolysi s, photodegradation in water, activated sludge sorption 5254 isotherm, biodegradability, and activated slud ge, respiration inhibition tests. 5255*** EO 12866 Draft – Do Not Cite, Quote or Release During Review *** 6. Adsorption and desorption usi ng a batch equilibrium method is 5256 preferred. In some cases, as when the antimicrobial pesticide degrades rapidly, 5257 soil column leaching with unaged or aged columns may be more appropriate to 5258 fully characterize the potential m obility of the parent compound and major 5259 transformation products. 5260 7. For industrial processes and water systems, aquatic areas, and the all 5261 other use patterns category (as specifi ed in § 158.2280(a)(3)), data are required 5262 based on a weight-of-evidence evaluation of the results of the hydrolysis, 5263 photodegradation in water, activated sludge sorption isotherm, biodegradability, 5264 and activated sludge, respir ation inhibition tests. 5265 8. The environmental media (soil, water, hydrosoil, and biota) to be 5266 utilized in these studies must be collected from areas represent ative of potential 5267 use sites. 5268 9. For industrial processes and water systems, and aquatic areas, data 5269 are required for use sites that are intermittently dry. 5270 10. For non

- metallic antimicrobials, Data are not required if the antimicrobial is 5271 an inorganic substance or a metal salt; or if the standardized soil profiles 5272 demonstrate that the ant imicrobial is likely to readily degrade either microbially or 5273 via redox reactions (chemically ). ) and no transformation/degradate/leachate 5274 products of concern (as described under § 158.2280(a)(2)) are produced. 5275 11. Analytical methods used to g enerate data associated with this study 5276 must include results of a successful conf irmatory method trial by an independent 5277 laboratory. 5278*** EO 12866 Draft – Do Not Cite, Quote or Release During Review *** 12. Protocols must be approved by the Agency prior to the initiation of the 5279 study. 5280 13. For industrial processes and water systems, wood preservatives, and 5281 the all other use patterns category (as specified in § 158.2280(a)(3)), data are 5282 required based on the potential for aquat ic exposure and if the weight-of5283 evidence indicates that the active ingr edient or principal transformation products 5284 are likely to have the potentia l for persistence, mobility, nontarget aquatic toxicity, 5285 or bioaccumulation. 5286 14. Data are required if the weight -of-evidence indicates that the active 5287 ingredient or principal tr ansformation products are likely to occur in nontarget 5288 freshwater, estuarine, or marine waters such that human or environmental 5289 exposures are likely to occu r. In making that dete rmination, the Agency takes 5290 into account other factors such as the toxicity of the chem ical(s), available 5291 monitoring data and the vulnerab ility of the freshwater, es tuarine, or marine water 5292 resources in the antimicrobial use area. 5293 15. For wood preservatives, an aquatic leaching study is required. A soil 5294 leaching study is required if human or environmental exposures are likely to 5295 occur from leachates that contain the acti ve ingredient or principal transformation 5296 products from wood treated with a preser vative product. Protocols must be 5297 approved by the Agency prior to t he initiation of the study. 5298 16. For antifoulant paints and coati ngs, a leaching study is required. 5299 Protocols must be approved by the Agency pr ior to the initiati on of the study. 5300*** EO 12866 Draft – Do Not Cite, Quote or Release During Review *** 17. Protocols, which include the residues of concern (such as parent, 5301 degradate/transformation product, and/or leachate residues) that would be 5302 monitored, must be approved by the Agency pr ior to the initiation of the study. 5303 18. A biodegradation study is not requi red if the antimic robial meets one 5304 or more of the following criteria: 5305 i. Classified as a metal ; , 5306 ii. Relatively volatile, but not hydrophobic ; , 5307 iii. Highly reactive , 5308 iv. Both the parent and all transformation/degradate products (as 5309 described under § 158.2280(a)(2)) have hal f-lives of less than 3 hours, 5310 v. None of the registered or pr oposed product uses would result in 5311 transport of the parent and its transformation/degradate products (as described 5312 under § 158.2280(a)(2)) to a wa stewater treatment plant

. 5313 19. The activated sludge sorption is otherm test is not required if the 5314 antimicrobial is: 5315 i. Relatively volatile, but not hydrophobic; 5316 ii. Highly reactive; or 5317 iii. The log K ow is less than 3.0. 5318 20. If the criteria of test note (19) of this par agraph are not met, then the 5319 activated sludge sorption isotherm test is re quired if one or mo re of the following 5320 criteria are also met: 5321 i. The antimicrobial is a metal

. , 5322 ii. The log K ow is greater than or equal to 3.0

. , 5323 iii. The antimicrobial is pos itively charged or polycationic

. , 5324*** EO 12866 Draft – Do Not Cite, Quote or Release During Review *** iv. The EC 50 in the activated sludge, respirat ion inhibition test is less than 5325 or equal to 20 mg/L

. , 5326 v. The EC 50 in the activated sludge, respirat ion inhibition test is greater 5327 than 20 mg/L, and the antimicrobial fa ils the ready biodegradability study. 5328 21. The activated sludge respiration inhi bition study is not required if none 5329 of the registered or proposed product uses would result in transport of the parent 5330 and its transformation/degradate products (as described under § 158.2280(a)(2)) 5331 to a wastewater treatment plant. 5332
§ 158.2290 Residue Chemistry 5333 (a) General . Subpart B of this part and §158.2201 describe how to use 5334 the table in paragraph (h) of this secti on to determine the residue chemistry data 5335 requirements for antimicrobial pesticide products. Notes that apply to an 5336 individual test including specific condition s, qualifications, or exceptions are listed 5337 in paragraph (i) of this section. 5338 (b) Residue chemistry data are required for: 5339 (1) Antimicrobial end-use products with uses that may result in residues in 5340 or on food including, but not limited to: 5341 (i) Products that require a tolerance, tolerance exemption, or food additive 5342 regulation or clearance. 5343 (ii) Products that may be used to tr eat livestock or poultry drinking water, 5344 for food egg washing, or fo r fruit and vegetable rinses. 5345 (iii) Products that may be applied to a surface or incorporated into a 5346 material that may contact food or feed. Data are required r egardless of whether 5347 the antimicrobial is ap plied or impregnated for t he purpose of imparting 5348*** EO 12866 Draft – Do Not Cite, Quote or Release During Review *** antimicrobial protection to external surfaces of the substance or article, or for the 5349 purpose of protecting the substance or article itself. 5350 (iv) Products that may be applied to wa ter that have the potential to result 5351 in residues in potable water, or in water used for livestock and poultry drinking 5352 water, irrigation of crops, or water c ontaining fish that may be used for human 5353 food. 5354 (v) Wood preservative or antif oulant products intended for treating 5355 submerged materials that may result in food contact (e.g., lobster pots, fish 5356 cages on fish farms). 5357 (2) Each manufacturing-use product bear ing directions fo r formulation into 5358 an end-use product bearing uses described in paragraph (b)(1) of this section. 5359 (c) Residue chemistr y data are not required under paragraph (b) of this 5360 section if no adverse effects (no toxici ty endpoints) are asso ciated with dietary 5361 exposure to the active ingr edient or if theoretical (h igh-end) dietary exposure 5362 estimates combined with the applicable toxicity endpoint result in acute and 5363 chronic dietary risks that are below the Agency levels of concern. 5364 (d) For purposes of this section, Magnitude of the Residue Studies 5365 include the following: Food-handling, mi gration studies, potable water, fish, 5366 irrigated crops, meat/milk/poultry/eggs, crop field trails, processed food or feed, 5367 and anticipated residues. 5368 (e) If the antimicrobial chemical ma y be applied to a field crop, then the 5369 residue chemistry data requi rements of §158.1410 apply. 5370 (f) The following term is defined fo r the purposes of this section: 5371*** EO 12866 Draft – Do Not Cite, Quote or Release During Review *** Residue of concern means the parent pesticidal compound and its metabolites, 5372 degradates, and impurities of toxicological concern. 5373 (g) Key. R = Required; CR = Conditionally required; NR = Not required; 5374 TGAI = Technical grade of the active i ngredient; TEP = Typical end-use product; 5375 PAI = Pure active ingredient; PAIRA = Pure active ingredient radiolabeled; ROC 5376 = Residue of concern. 5377*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***(h)Antimicrobial residue chemistry data requirementstable.The following table shows the data requirements for5378residue chemistry. The test notes appearin paragraph (i) of this section.5379Table -- Antimicrobial ResidueChemistry Data Requirements5380GuidelineNumberData Requirement Uses TestSubstanceTest NoteNo.AgriculturalPremiseIndirect Food Direct Food AquaticSupporting Information860.1100 Chemical identity R R R R TGAI --860.1200 Directions for use R R R R -- --860.1550 Proposedtolerance/toleranceexemptionRRRR--1860.1560 Reasonable groundsin support of petitionRRRR--1860.1650 Submittal of analyticalreference standardsRRRRPAI/ROC2Food-Contact Surfaces Or Impregnated Materials860.1460 Food-handling CR CR CR CR TEP 3NoneNature of residue onsurfacesCRCRCRCRPAIRA orTGAI4None Migration studies CR CR CR CR TEP 5860.1340Residue analyticalmethod for datacollectionCRCRCRCRROC6860.1380 Storage stability R R R R TEP or ROC 7Higher tiered860.1300Nature of the residuein plantsCRCRCRCRPAIRA8860.1300Nature of the residuein livestockCRCRCRCRPAIRA9860.1340Residue analyticalmethods fortolerance/toleranceCRCRCRCRROC10*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***exemptionenforcement860.1360 Multiresidue methodtestingCR CR CR CR ROC 11860.1400 Potable water CR CR CR CR TEP 12860.1400 Fish CR CR CR CR TEP 13860.1400 Irrigated cropsCR CR CR CR TEP 14860.1480 Meat/milk/poultry/eggsCR CR CR CR TGAI or ROC 15860.1500 Crop field trials CR CR CR CR TEP 16860.1520 Processed food orfeedCR CR CR CR TEP 17None Anticipated residues CR CR CR CR ROC 185381(i) Test notes. The following test notes appl y to the data requirements in 5382 the table to paragraph (h) of this section: 5383 1. A petition proposing a numerical to lerance or a tolerance exemption is 5384 required for any food or feed use subject to section 408 of FFDCA if the use is 5385 not covered by an existing tolerance or tole rance exemption. If the use is subject 5386 to FFDCA section 409, the applicant mu st identify to EPA an applicable section 5387 409 food additive regulation or clearance, or submit a copy of a petition to FDA 5388 requesting a section 409 food additive regul ation or clearance for the food or 5389 feed use. 5390 2. An analytical reference standard is required for any food or feed use 5391 requiring a numeric tolerance or exemption. Material safety data sheets as 5392 specified by the Occupational Safety and Health Administration in 29 CFR 5393 1910.1200 must accompany analytical standards. 5394 3. Data are required if a pes ticide may be used in a food-handling 5395 establishment unless data including, but not limited to, theor etical (high-end) 5396 estimates, radiolabeled l aboratory data, or the nature of the residue on surfaces 5397 study show that residues will not occur in food or feed. 5398 4. If an antimicrobial pesticide may be applied to a food-c ontact surface or 5399 impregnated into a food-contact material and if theoretical (high-end) estimates 5400 of exposure exceed EPA’s risk level of c oncern, then the natur e of the residue on 5401 surfaces study is required. Protocols must be approved by the Agency prior to 5402 the initiation of the study. 5403*** EO 12866 Draft – Do Not Cite, Quote or Release During Review *** 5. Based on the results of the nature of the residue on surfaces study, if 5404 residues of concern are identified, then the migration study will be required. 5405 Protocols must be approved by the Agency pr ior to the initiati on of the study. 5406 6. If a magnitude of the residue study , as specified in § 158.2290(d), is 5407 required, then a residue anal ytical method suitable for collecting data is also 5408 required. The method must be capable of determining all residues of concern, to 5409 permit calculation of dietary risk or to establish a tolerance or tolerance 5410 exemption. 5411 7. If a magnitude of the residue study , as specified in § 158.2290(d), is 5412 required, then storage stabilit y data are also required, unless analytical samples 5413 are stored for 30 days or less. If, during hazard characterization, a residue has 5414 been identified as “of concern” and is know n to be volatile or labile, then storage 5415 stability data are requi red regardless of sample storage time. 5416 8. If crop plants or met abolically active raw agricultural commodities of 5417 food crops may be directly or indirect ly exposed to an antimicrobial, plant 5418 metabolism studies are required to dete rmine the transformation products that 5419 may enter the human diet. Such exposure could include, but is not limited to: 5420 i. Treatment of storage or shipping containers, 5421 ii. Postharvest fruit and vegetable treat ment prior to shipping or storage, 5422 iii. Use of antimicrobial-tr eated water for irrigation, and 5423 iv. Any direct food contact use. 5424 9. If livestock may be ex posed to an antimicrobial, then hen and ruminant 5425 metabolism studies are required to dete rmine the identities of residues of 5426 concern that may enter the human di et from consumption of livestock 5427*** EO 12866 Draft – Do Not Cite, Quote or Release During Review *** commodities. Livestock may be exposed via the oral, dermal, or inhalation route 5428 following treatment or cont amination of sites includ ing, but not limited to, 5429 livestock premises, feed, and drinking water. Shell eggs and other metabolically 5430 active livestock products may also be tr eated. If livestock may be exposed to 5431 one or more residues of concern differi ng from those found in animals, then one 5432 or more additional livestock metabolis m studies involving dosing with these 5433 residues may be required. 5434 10. If there is a numerical tolera nce or tolerance exemption level to 5435 enforce, then a residue analytical method suitable for enforcement purposes is 5436 required. The method must be suppor ted by an independent laboratory 5437 validation. 5438 11. If there is a numerical tolera nce or tolerance exemption level to 5439 enforce, then testing is required to determine whether the Food and Drug 5440 Administration/United States Department of Agricultur e multiresidue methodology 5441 would detect and identify the antimicrobial a nd its residues of concern, as part of 5442 programs to monitor pesticides in the U.S. food supply. 5443 12. Data are required if an antimicr obial may be applied directly to water 5444 or if there is the potentia l that the antimicrobial-tr eated water could be used 5445 directly for drinking water purposes by humans or animals or that contaminated 5446 water could run-off, leach, or be disc harged from treated site s or materials and 5447 make its way into potable water. 5448 13. Data are required if an antimicr obial may be applied directly to water 5449 inhabited by fish or that will be inhabited by fish or if contaminated water could 5450*** EO 12866 Draft – Do Not Cite, Quote or Release During Review *** run-off, leach, or be discharged from tr eated sites or materials and make its way 5451 into bodies of water contai ning fish that may be used for human consumption. 5452 14. Data are required if an antimicr obial may be applied directly to water 5453 used for irrigation of food crops or such that contaminated water could run-off, 5454 leach, or be discharged from treated sites or materials to make its way into water 5455 used for irrigation of food crops. 5456 15. If the antimic robial may be applied directly to livestock, metabolically5457 active livestock commodities (e.g., eggs), livestock feed or drinking water, or 5458 livestock premises, or a livestock metabolis m study indicates that residues of the 5459 antimicrobial may result in livestock commodities, studies are required to 5460 determine the magnitude of the residues of concern in fat, meat, meat by5461 products, milk, poultry, and eggs that may be consumed by humans. These 5462 studies, however, may not be required in cases where the livestock metabolism 5463 studies indicate that transfer of pestici de residues of concern to tissues, milk, and 5464 eggs is not expected to occur at the maximum expected expos ure level for the 5465 animals. 5466 16. If food crops or raw agricultura l commodities of food crops may be 5467 exposed to an antimicrobial, then resi due studies are required to determine the 5468 magnitude of the residues of concern that may enter the human diet. Such 5469 exposures include, but are not limit ed to, postharvest fruit and vegetable 5470 treatments and applicati on of antimicrobial chemicals to field crops, mushroom 5471 houses, empty or occupied beehives, or wood used to construct beehives. 5472 17. Data on the nature and magnitude of residues in processed food or 5473 feed are required if antimicrobial re sidues could potentially concentrate on 5474*** EO 12866 Draft – Do Not Cite, Quote or Release During Review *** processing. If so, the est ablishment of a separate tolerance higher than that in 5475 the raw agricultural commodity may be required. 5476 18. Data are required when dietary ex posure values at the tolerance level 5477 or screening-level (high-end) result in esti mates of dietary or aggregate risk that 5478 meet or exceed the Agency’s level of c oncern. These data may include, but are 5479 not limited to, washing, cooking, proce ssing, or degradation studies as well as 5480 market basket surveys for a more realis tic residue determination. Protocols must 5481 be approved by the Agency prior to the initiation of the study. 5482 PART 161—[AMENDED] 5483 7. The authority citation for part 161 continues to read as follows: 5484 Authority: 7 U.S.C. 136 – 136y. 5485 Part 161 [Removed] 5486 8. Remove part 161 is removed:

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