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1 EO 12866_Antimicrobial Data Requirements_RIN 2070-AD30_FRM_2011-09-19.docx 

2 Draft document submitted Interagency review. 

3 BILLING CODE 6560–50–P 

4 ENVIRONMENTAL PROTECTION AGENCY 

5 40 CFR Part 158 and 161

6 EPA–HQ–OPP–2008–0110; FRL–XXXX–X

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 reflect current scientific and regulatory practices. 

13 Besides providing the regulated community with clearer and more transparent 

14 information, the updated data requirements further enhance EPA’s ability to make 

15 regulatory decisions about the human health, and environmental fate and effects 

16 of antimicrobial pesticide products. 

17 DATES: This final rule is effective [insert date 60 days after date of publication in 

18 the Federal Register]. 

19 ADDRESSES: EPA has established a docket for this action under docket 

20 identification (ID) number EPA–HQ–OPP–2008–0110. All documents in the 

21 docket are listed in the docket index available at http://www.regulations.gov. 

22 Although listed in the index, some information is not publicly available, e.g., 

23 Confidential Business Information (CBI) or other information whose disclosure is 

24 restricted by statute. Certain other material, such as copyrighted material, is not 
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25 placed on the Internet and will be publicly available only in hard copy form. 

26 Publicly available docket materials are available in the electronic docket at 

27 http://www.regulations.gov, or, if only available in hard copy, at the OPP 

28 Regulatory Public Docket in Rm. S–4400, One Potomac Yard (South Bldg.), 2777 

29 S. Crystal Dr., Arlington, VA. The Docket Facility is open from 8:30 a.m. to 4 p.m., 

30 Monday through Friday, excluding legal holidays. The Docket Facility telephone 

31 number is (703) 305–5805. 

32 FOR FURTHER INFORMATION CONTACT: Kathryn Boyle, Field and External 

33 Affairs Division (7506P), Office of Pesticide Programs, Environmental Protection 

34 Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460–0001; telephone 

35 number: (703) 305-6304; e-mail address: boyle.kathryn@epa.gov, or contact 

36 Scott Drewes, same address; telephone number (703) 347-0107; email address: 

37 drewes.scott@epa.gov. 

38 SUPPLEMENTARY INFORMATION: 

39 I. General Information 

40 A. Does this Action Apply to Me? 

41 You may be affected by this action if you are a producer of pesticide 

42 products (NAICS 32532), antifoulants (NAICS 32551), antimicrobial pesticides 

43 (NAICS 32561) or wood preservatives (NAICS 32519), importers of such 

44 products, or any person or company who seeks to register an antimicrobial, 

45 antifoulant coating, ballast water treatment, or wood preservative pesticide or to 

46 obtain a tolerance for such a pesticide. This listing is not intended to be 

47 exhaustive, but rather provides a guide for readers regarding entities likely to be 
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48 affected by this action. Other types of entities not listed above could also be 

49 affected. The North American Industrial Classification System (NAICS) codes 

50 have been provided to assist you and others in determining whether this action 

51 might apply to certain entities. If you have any questions regarding the 

52 applicability of this action to a particular entity, please contact Nader Elkassabany, 

53 Chief of the Risk Assessment and Science Support Branch in the Antimicrobials 

54 Division of the Office of Pesticide Programs at (703) 308-8783 or via email, 

55 elkassabany.nader@epa.gov. 

56 B. How Can I Access Electronic Copies of this Document? 

57 

58 In addition to accessing an electronic copy of this Federal Register document through 

59 the electronic docket at http:// www.regulations.gov, you may access this Federal Register 

60 document electronically through the EPA Internet under the ‘‘Federal Register’’ listings at 

61 http://www.epa.gov/fedrgstr. You may also access a frequently updated electronic version of 40 

62 CFR parts 158 and 161 through the Government Printing Office’s pilot e-CFR site at http:// 

63 www.gpoaccess.gov/ecfr. To access the harmonized test guidelines referenced in this document 

64 electronically, please go to http://www.epa.gov/ocspp and select “Test Methods and Guidelines.” 

65 II. Background 

66 A. What Action is the Agency Taking? 

67 The Environmental Protection Agency (EPA or the Agency) is revising and 

68 updating the data requirements for antimicrobial pesticides in Title 40 of the Code 

69 of Federal Regulations (CFR) in subpart W of part 158. Subpart W sets out data 

70 requirements specific to antimicrobial products that are described by the 

71 antimicrobial use patterns and use exposure considerations particular to 

72 antimicrobials. With the promulgation of part 158, subpart W, EPA is removing 
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73 part 161, entitled “Data Requirements for Registration of Antimicrobial Pesticides” 

74 as it is no longer needed. 

75 Antimicrobial pesticides are used to control microbiological contamination 

76 in healthcare applications, and deterioration in industrial, commercial, and 

77 consumer products. Nearly 60 percent of antimicrobial products are registered as 

78 public health products (as defined at FIFRA 2(gg)) to control infectious 

79 microorganisms in hospitals and other health care environments. Public health 

80 products are intended to control microorganisms infectious to humans in any 

81 inanimate environment. The common public health antimicrobial products include 

82 sterilants, disinfectants, and sanitizers. Nonpublic health products are sold and 

83 distributed for use to control growth of algae, odor-causing bacteria, bacteria 

84 which cause spoilage, deterioration or fouling of materials and microorganisms 

85 infectious only to animals. Other examples of nonpublic health products include 

86 products used in cooling towers, jet fuel, paints, and treatments for textile and 

87 paper products 

88 Within this final rule EPA is using the term antimicrobials to collectively 

89 refer to antimicrobial pesticides, antifoulant coatings and paints, and wood 

90 preservatives. 

91 B. What is the Agency's Authority for Taking this Action? 

92 This action is issued under the authority of sections 2, 3, 4, 5, 10, 12, and 

93 25 of the Federal Insecticide and Rodenticide Act (FIFRA) as amended and 

94 section 408 of the Federal Food, Drug, and Cosmetic Act (FFDCA). The data 

95 required for a registration, reregistration, experimental use permit (EUP), or 

96 tolerance/tolerance exemption for antimicrobials are listed in 40 CFR part 158. 
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97 C. Next Steps after this Rulemaking 

98 Over the next several years, EPA’s Office of Pesticide Programs (OPP) is 

99 committed to improving and transforming our approach to pesticide risk 

100 management by enhancing our ability to use integrated approaches to testing and 

101 assessment. Over the next 5 years, the Pesticide Program plans to maximize use 

102 of existing data from similar compounds, including information from new in silico

103 and in vitro predictive models and exposure modeling to target in vivo toxicity 

104 testing that is needed to assess and manage chemical risks appropriately. 

105 Over the next decade, as experience is gained and as our understanding of 

106 toxicity pathways increases, an enhanced integrated testing and assessment 

107 approach will be implemented for all pesticides. The approach will fully integrate 

108 hazard and exposure information using advanced computer modeling of new in 

109 vitro data and an understanding of toxicity pathways to better predict risks and to 

110 determine what additional data are necessary to provide a sound basis to manage 

111 risks of concern. Data from improved biomarkers of exposure and biological 

112 outcomes from population-based studies will be used to evaluate the 

113 effectiveness of this new risk assessment paradigm, to readily identify early 

114 effects in exposed populations, and to improve the approach. 

115 Current Agency scientific and regulatory practice provides the foundation 

116 for this final rule. While current practice is still largely dependent on animal (in 

117 vivo) testing, this rule is one milestone towards the Agency’s longer term vision for 

118 21st Century Toxicology and new integrated testing strategies. OPP believes that 

119 certain classes of chemicals, such as antimicrobial pesticides, provide an 
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120 appropriate starting point for OPP’s planned transformation. Many antimicrobials 

121 have both pesticidal and non-pesticidal uses. In addition, many antimicrobial 

122 products are regulated under multiple jurisdictions. Thus, many antimicrobial 

123 chemicals have been assessed by other regulatory programs and agencies. The 

124 ready availability of published literature and publicly-available assessments offer a 

125 unique opportunity for the applicant to use the available information as a starting 

126 point for fulfilling data requirements, and, when appropriate, to use computer 

127 modeling and/or in-vitro data to supplement or fulfill data requirements. For 

128 example, OPP established a voluntary pilot program for eye irritation testing of 

129 certain antimicrobial pesticides using non–animal test methods. OPP will 

130 continue to evaluate use of new in vitro and computer-based approaches in our 

131 hazard and risk assessment processes as the technologies are sufficiently 

132 developed and peer-reviewed. Certain tools are already available or anticipated 

133 to become available in the near term including, (Quantitative) Structure-Activity134 Relationship (Q)SAR/expert systems and in vitro high through put screening 

135 technologies. Furthermore, in conjunction with the International Life Sciences 

136 Institute (ILSI), OPP is currently pursuing the development of an application of the 

137 thresholds of toxicological concern (TTC) concept to evaluate antimicrobial 

138 pesticides. In collaboration with OPP, EPA’s Office of Research and 

Development is providing momentum for achieving the vision of 21st 139 Century 

140 Toxicology by developing and evaluating new technologies in molecular, cellular, 

141 and computational sciences to supplement or replace more traditional methods of 

data development. OPP believes that its goal of using 21st 142 Century science in 
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143 integrated approaches to testing and assessment is achievable with strong 

144 scientific and stakeholder support through a transparent process. As the 

145 enhanced integrated testing and assessment approach matures, based on these 

146 scientific advances, EPA may determine to update its data requirements to reflect 

147 evolving program needs as specified in § 158.30(c). 

148 D. Acronyms Used in this Document 

149 The acronyms used throughout this document have the following meaning: 

150 ACGIH means the American Conference of Governmental and Industrial 

151 Hygenists 

152 AD means EPA’s Antimicrobial Division in OPP 

153 ARTCA means the Antimicrobial Regulation Technical Correction Act 

154 ASRI means Activated Sludge, Respiration Inhibition Test 

155 ASSI means Activated Sludge Sorption Isotherm 

156 ASTM means the American Society for Testing and Materials 

157 AWPA means the American Wood Protection Association, formerly American 

158 Wood Preservatives Association 

159 “CR” means conditionally required 

160 CFR means the Code of Federal Regulations 

161 CDC means the Centers for Disease Control and Prevention 

162 COC means concentration of concern 

163 CWA means the Clean Water Act 

164 DCI means Data Call-in 

165 D-t-D means down the drain 
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166 EA means economic analysis 

167 EDSP means Endocrine Disrupter Screening Program 

168 E-FAST means Exposure and Fate Assessment Screening Tool 

169 EP means end-use product 

170 EPA or the Agency means the United States Environmental Protection Agency 

171 ESA means the Endangered Species Act 

172 EU means the European Union 

173 EUP means experimental use permit 

174 FDA means the Food and Drug Administration 

175 FIFRA means the Federal Insecticide, Fungicide and Rodenticide Act 

176 FFDCA means the Federal Food Drug and Cosmetic Act 

177 FQPA means the Food Quality Protection Act 

178 FWS means the United States Fish and Wildlife Service 

179 HHS means the United States Department of Health and Human Services 

180 HSRB means the Human Studies Review Board 

181 ICR means Information Collection Request 

182 ILSA means International Life Sciences Institute 

183 Kd means soil partition coefficient 

184 Koc means soil organic carbon-water coefficient 

185 Kow means octanol-water partition coefficient 

186 MOR means magnitude of the residue 

187 mg/L means milligrams per liter 

188 NAICS means the North American Industrial Classification System 
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189 NAS means the National Academy of Sciences 

190 NMFS means the United States National Marine Fisheries Service 

191 NPDES means National Pollution Discharge Elimination System 

192 NPRM means Notice of Proposed Rulemaking 

193 “NR” means not required 

194 OCSPP means EPA’s Office of Chemical Safety and Pollution Prevention, 

195 formerly Office of Pollution Prevention and Toxics (OPPTS) 

196 OECD means Organisation for Economic Cooperation and Development 

197 OMB means Office of Management and Budget 

198 OPP means EPA’s Office of Pesticide Programs 

199 OPPT means EPA’s Office of Pollution Prevention and Toxics 

200 OSHA means Occupational Safety and Health Administration 

201 OW means EPA’s Office of Water 

202 PPCP means pharmaceuticals and personal care products 

203 PEL means permissible exposure limit 

204 ppb means parts per billion 

205 ppm means parts per million 

206 PPE means personal protective equipment 

207 PRA means the Paperwork Reduction Act 

208 PRIA means the Pesticide Registration Improvement Act 

209 POTW means publicly owned treatment works 

210 QSAR or (Q)SAR means quantitative structure-activity-relationships 

211 “R” means required 
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212 RAC means raw agricultural commodity 

213 RED means Reregistration Eligibility Decision Document 

214 RFA means the Regulatory Flexibility Act 

215 RfC means Reference Concentration 

216 RfD means Reference Dose 

217 ROC means residue of concern 

218 RQ means risk quotient 

219 SAP means the FIFRA Scientific Advisory Panel 

220 SAR means structure-activity-relationships 

221 SBREFA means the Small Business Regulatory Enforcement Fairness Act 

222 TGAI means technical grade active ingredient 

223 TTC means threshold of toxicological concern 

224 TEP means typical end-use product 

225 TLV means threshold limit value 

226 WET means whole effluent testing 

227 WOE means weight-of-evidence 

228 WQC means Water Quality Criteria 

229 WQS means Water Quality Standards 

230 WWTP means wastewater treatment plant 

231 USDA means United Stated Department of Agriculture 

232 III. History of this Rulemaking 

233 A. Background 
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234 EPA’s data requirements for pesticides were first published in 1984. Those 

235 data requirements were primarily influenced by agricultural uses. Since then, new 

236 risk concerns have been identified, and EPA’s statutory mandates for pesticide 

237 registration under FIFRA and tolerance-setting under the FFDCA were amended 

238 in 1996 to require EPA to update the scientific underpinnings of risk assessments. 

239 The Agency must now perform more in-depth risk analyses, such as aggregate 

240 and cumulative risk assessments. 

241 On October 26, 2007, EPA promulgated final rules updating the data 

242 requirements for conventional pesticides (72 FR 60934), and biochemical 

243 pesticides and microbial pesticides (72 FR 60988). The rule development 

244 process for part 158, subpart W used the updated conventional pesticides data 

245 requirements as the starting point while considering the case-by-case data 

246 requirement decisions made over the years of registering antimicrobial pesticide 

247 products. Four of the other subparts in part 158, promulgated in 2007, also apply 

248 to antimicrobial pesticides (see 40 CFR 158.1). Those four subparts are: 

249  Subpart A: General Provisions 

250  Subpart B: How to Use Data Tables 

251  Subpart C: Experimental Use Permits 

252  Subpart D: Product Chemistry 

253 As part of promulgating those final rules, on October 24, 2007, (72 FR 

254 60251) EPA preserved the original part 158 data requirements (promulgated in 

255 1984), by redesignating them as part 161, to provide continued regulatory 

256 coverage for antimicrobial pesticides until the Agency could promulgate a final 
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257 regulation for antimicrobial pesticides. This final rule finishes the promulgation of 

258 a final regulation for antimicrobial pesticides. Accordingly, EPA is also revoking 

259 part 161 today. 

260 B. Discussion of the October 8, 2008 Notice of Proposed Rulemaking (NPRM) 

261 EPA published an NPRM on October 8, 2008, (73 FR 59382) proposing to 

262 establish data requirements specific to the registration of antimicrobial pesticide 

263 products in 40 CFR part 158, subpart W. The closing date of the 90–day 

264 comment period for the NPRM was January 6, 2009. The comment period was 

265 extended to April 6, 2009, to allow stakeholders additional time to assess the 

266 impact of the proposed revisions on their particular situations and submit their 

267 comments. In addition, EPA convened a public workshop in Arlington, Virginia, to 

268 explain the provisions of the NPRM on November 6, 2008. The proposed rule, 

269 the notice of the extension of the comment period, the notice of the public 

270 meeting, the presentations used at the public meeting, the comments submitted, 

271 and EPA’s Response to Comments Document are available to the public at 

272 http://www.regulations.gov (see docket EPA-HQ-OPP–2008–0110). 

273 C. Comments Submitted to EPA. 

274 During the public comment period, EPA received comments on the 

275 proposed part 158, subpart W regulations from 29 entities. The breakdown of the 

276 origin of the comments is as follows: 

277  Antimicrobial Industry – 15 

278 o Lanxess Corporation 

279 o S.C. Johnson & Sons, Inc. 
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280 o Scientific and Regulatory Consultants, Inc. 

281 o Antimicrobial Exposure Joint Venture (AEJV) 

282 o Consumer Specialty Products Association (CSPA) 

283 o Ecolab Inc. 

284 o ISSA 

285 o The Clorox Company 

286 o Reckitt Benckiser 

287 o Mason Chemical Company 

288 o Proctor & Gamble 

289 o Dow Chemical Company 

290 o Johnson Diversey 

291 o Troy Corporation 

292 o American Chemistry Council (ACC) 

293  Non-Governmental Organizations (NGOs) – 3 

294 o Environmental Working Group 

295 o Humane Society 

296 o Beyond Pesticides 

297  Other – 3 

298 o CropLife America 

299 o Innovation and Reform Group 

300 o Alternative Testing Working Group 

301  Foreign Government Entity - 1 

302 o Health Canada 
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303  Water Agencies – 7 

304 o Hampton Roads Sanitation District 

305 o California Association of Sanitation Agencies 

306 o National Association of Clean Water Agencies 

307 o San Francisco Department of the Environment 

308 o Sanitation Districts of Los Angeles County 

309 o Tri-Tac 

310 o California Stormwater Quality Association 

311 There were also late comments from ACC, received at meetings held at 

312 EPA in Arlington, VA on December 2, 2009, and June 14, 2010. Most recently, at 

313 a meeting on May 17, 2011, and in a letter dated June 17, 2011, both ACC and 

314 CSPA provided additional late comments. The presentation materials and EPA’s 

315 summary of the meetings, and the letter with attachments are included in the 

316 docket at http://www.regulations.gov. The late comments submitted by ACC 

317 and/or CSPA were not new comments, but rather re-statements of issues 

318 presented in their original comments submitted to EPA. 

319 A late comment cosigned by the Physicians Committee for Responsible 

320 Medicine, the Humane Society International, and People for the Ethical Treatment 

321 of Animals was submitted on September 1, 2010. This late comment did contain 

322 several new issues, which were addressed by adding the additional comments 

323 and responses to the toxicology section of the Response to Comments 

324 Document. 
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325 EPA carefully reviewed all comments submitted. The Response to 

326 Comments Document is in the docket at http://www.regulations.gov. As 

327 previously discussed, the Response to Comments Document contains the 

328 rationale for the changes that were made from the proposed rule to the final rule, 

329 in response to submitted comments. Similar comments are grouped together. 

330 EPA selected the most significant of the comments, such as those that impacted 

331 the changes from the proposed rule to the final rule, for inclusion in Units IV to 

332 XXII of this final rule. 

333 D. This Final Rule 

334 1. In general. This final rule reflects updates and revisions to part 161, in 

335 many cases by codifying the case-by-case data requirements decisions made 

336 over the years to help apply the agriculturally-based 1984 data requirements to 

337 antimicrobial pesticide products. The antimicrobial data requirements are being 

338 added to part 158, subpart W. Part 161 is being removed. This final rule will 

339 further enhance the Agency's ability to make regulatory decisions about the 

340 human health, and environmental fate and effects of antimicrobial pesticide 

341 products. 

342 Based on comments received, EPA revised the proposed data tables. 

343 EPA’s Response to Comments Document is in the docket at 

344 http://www.regulations.gov. That document contains the rationale for the changes 

345 that were made from the proposed rule to the final rule, in response to submitted 

346 comments. 
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347 Eleven new data requirements are being codified today. As discussed in 

348 the preamble to the proposed rule (73 FR 59387), a “new” data requirement 

349 “means that the data requirement has never been required or has rarely been 

350 required on a case-by-case basis, and has not been routinely considered during 

351 the Agency’s evaluation of the data needed for the purpose of risk assessment.” 

352 Eight new data requirements that were proposed in 2008 and are now being 

353 codified are: Developmental neurotoxicity; immunotoxicity; photodegradation in 

354 soil; soil residue dissipation; ready biodegradability study; porous pot study; 

355 activated sludge sorption isotherm study; and modified activated sludge, 

356 respiration inhibition test. The developmental neurotoxicity and immunotoxicity 

357 tests are new compared to part 161, but were added for conventional pesticides in 

358 the 2007 amendments to part 158. The photodegradation in soil study was not 

359 previously required for wood preservatives. The other four studies are unique to 

360 antimicrobials. 

361 Since the proposed rule, based on comments received, three new data 

362 requirements are also being added: Simulation tests to assess the 

363 biodegradability of chemicals in discharged wastewater, simulation test – aerobic 

364 sewage treatment: activated sludge units, and nature of the residue on surfaces. 

365 Additionally, this final rule: 

366  Codifies data requirements/use pattern combinations that were not codified 

367 in part 161, but have typically been required to register an antimicrobial pesticide 

368 product. 
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369  Provides improved definitions for antimicrobial pesticides used for public 

370 health and nonpublic health purposes. 

371  Codifies data requirements to determine risks to waste water treatment 

372 plants (WWTPs) and the potential for movement of antimicrobials and their 

373 degradates from the indoor environment to the outdoor environment via effluent 

374 discharge from a publically owned treatment work (POTW). 

375 The data requirements promulgated today identify the types of information 

376 that EPA needs to determine whether a pesticide product should be registered, 

377 and make decisions regarding tolerances or tolerance exemptions for pesticide 

378 residues in food. Subpart W includes a series of tables and regulatory text that 

379 mirrors the data requirements for conventional pesticide. However, subpart W 

380 establishes specific data requirements for each scientific discipline (except 

381 product chemistry) for antimicrobial pesticides. As explained in Unit IIIA., subpart 

382 D to part 158, which contains the product chemistry data requirements for 

383 conventional pesticides, also applies to antimicrobials. The order of subpart W 

384 also mirrors that of the larger part 158. As such, the following data requirements 

385 categories are included in detail in part 158, subpart W: Product performance, 

386 hazard/toxicity (both human health and ecological toxicity), exposure (both 

387 application and post-application human exposures), residue chemistry, and 

388 environmental fate requirements. 

389 EPA is also codifying 12 antimicrobial use patterns, as described in the 

390 proposed rule (73 FR 59389-90, October 8, 2008). As part of today’s action EPA 
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391 has developed and will shortly post on the Agency’s website an Antimicrobial Use 

392 Site Index to provide additional information about these use patterns. 

393 As promulgated, subpart W is intended to improve the scientific basis for 

394 antimicrobial pesticide decisions. These efforts are expected to help protect 

395 human health and the environment by providing an up-to-date scientific 

396 framework for identifying and assessing the risks of antimicrobial pesticides sold 

397 or distributed in the United States. 

398 2. Changes to the proposed rule. In response to comments, EPA has 

399 made numerous changes to the proposed rule in crafting the final rule 

400 promulgated today. The most significant changes are summarized below. 

401 i. Alternatives to the porous pot study. With regard to the porous pot study 

402 in the final Environmental Fate Data Requirements Table in § 158.2280, EPA is 

403 adding two simulation studies that can serve as an alternative to the porous pot 

404 study. This change was based on a comment that requested consideration of 

405 whether “studies that simulate wastewater treatment plants (WWTPs) [could] 

406 substitute for [the porous pot study].” (ACC Comment in the docket at 

407 http://www.regulations.gov; document EPA-HQ-OPP-2008-0110-0088.9; 

408 Appendix H, entitled “Comments on Proposed Data Requirements for 

409 Environmental Fate” p. 5). Additionally, in the commenter’s suggested 

410 environmental fate data requirements table (p. 11), instead of giving the title of the 

411 study as “Porous Pot,” the commenter wrote “Simulated WWTP; e.g., Porous Pot 

412 Study.” 
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413 EPA agreed with the commenter and identified two other studies: The 

414 biodegradation in activated sludge study as described in the OPPTS guideline 

415 entitled “Simulation Tests to Assess the Biodegradability of Chemicals Discharged 

416 in Wastewater” and simulation test – aerobic sewage treatment: activated sludge 

417 units. This change provides applicants with more flexibility in meeting this data 

418 requirement. EPA’s rationale is described in Unit XV.A, and for greater detail see 

419 response to comment 134.1 in the Response to Comments Document in the 

420 docket at http://www.regulations.gov). Testnote 3 to the final Environmental Fate 

421 Data Requirements Table in § 158.2280 clearly specifies that only one 

422 biodegradation study is to be submitted. 

423 ii. Trigger for migration study. EPA made changes to the trigger for the 

424 migration study in the final Residue Chemistry Data Requirements in § 158.2290. 

425 In its proposed rule, EPA “triggered” the migration study based on anticipated 

426 instances such as theoretical (modeled) estimates yielding a risk of concern. One 

427 commenter submitted a suggested residue chemistry data requirements table with 

428 a line-item entitled “Nature of residue of surface.” (ACC Comment in the docket at 

429 http://www.regulations.gov; document EPA-HQ-OPP-2008-0110-0088.10; 

430 Appendix I, entitled “Comments on Proposed Data Requirements for Residue 

431 Chemistry” p. 7). A different commenter also submitted a different residue 

432 chemistry data requirements table, which also included the same line-item entitled 

433 “Nature of residue on surface.” (CSPA Comment in the docket at 

434 http://www.regulations.gov; document EPA-HQ-OPP-2008-0110-0086.2). 
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435 The commenters’ suggestion of requiring a nature of the residue study on 

436 surfaces provides a more definitive trigger for the migration study. EPA is adding 

437 a nature of the residue on surfaces study. As specified in testnote 3 to the final 

438 Residue Chemistry Data Requirements Table, the results of the nature of the 

439 residue on surfaces study will serve as a trigger for determining whether the 

440 migration study will need to be performed. EPA considers the commenters’ 

441 suggestion to be a valuable addition to the final Residue Chemistry Data 

442 Requirements Table in § 158.2290 that provides more definitive triggers to help 

443 define and narrow the instances of higher-tiered testing. 

444 iii. Changes to data requirements for wood preservatives. As discussed in 

445 Unit VI.B, EPA’s current practice of determining the data required for a wood 

446 preservative product is dependent upon where the product is intended to be used 

447 (land-only versus land and aquatic). This approach also assumes that diversion 

448 does not occur and that wood that is treated for land-only uses does not end up in 

449 the water and vice versa. In practice, it is difficult to assure that diversion does 

450 not occur. Accordingly, in response to comments, the Agency determined that all 

451 treated wood needs to be considered as having the potential to come into contact 

452 with surface water. Therefore, for the final Environmental Fate Table, for the 

453 wood preservatives column, the data requirements for anaerobic soil metabolism, 

454 aerobic aquatic metabolism, and anaerobic aquatic metabolism were changed 

455 from “CR” to “R.” For the final Nontarget Organism Table, for the wood 

456 preservatives column, the data requirements for chronic toxicity testing with fish 

457 (fish early-life stage) and aquatic invertebrate (aquatic invertebrate life-cycle) are 
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458 being changed from “CR” to “R” to provide chronic data when chronic exposure is 

459 expected. With regards to the three acute toxicity tests conducted with the TEP, 

460 the “NR” in the wood preservatives column is changed to “CR.” Additionally, EPA 

461 will perform a down-the-drain analysis for every product with an applicable use or 

462 exposure scenario, including wood preservatives, that has the potential for waters 

463 containing antimicrobials to reach a WWTP. Therefore, to perform this analysis, 

464 the Agency is requiring data on the biodegradation of a wood preservative and its 

465 potential toxicity to WWTP microorganisms in an activated sludge basin. 

466 iv. Changes to data requirements for antifoulants. Antifoulants are 

467 released/applied directly to the aquatic environment. These products are often 

468 manufactured to be persistent, and because of the continuous release process, 

469 some of the active ingredient is likely to be transferred to the bottom of the water 

470 column, and then be adsorbed to the sediment. Therefore, EPA is changing, in 

471 the final Environmental Fate Data Requirements Table, the “CR” for the aquatic 

472 sediment study for the antifoulant paint and coatings column to “R.” With regards 

473 to the three acute toxicity tests conducted with the TEP, the “NR” in the antifoulant 

474 paint and coatings column is changed to “CR.” Also, to perform a down-the-drain 

475 analysis, the Agency is requiring data on the biodegradation of an antifoulant and 

476 its potential toxicity to WWTP microorganisms in an activated sludge basin. 

477 v. Non-dietary ingestion. EPA proposed to require this post-application 

478 exposure study. However, EPA agrees that instead of requiring this study, it is 

479 more likely that EPA would model this route and pathway of exposure using inputs 
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480 from available and reliable published research. Therefore, EPA has removed this 

481 data requirement from the final Post-Application Exposure Table. 

482 vi. Re-structuring of proposed toxicology and residue chemistry data 

483 requirement tables. 

484 In the proposed rule, for the toxicology data requirements table, EPA separated 

485 those use patterns needing more toxicology data from those needing less 

486 toxicology data using a terminology described as high or low. Based on 

487 comments received, in this final rule, EPA is now using a food/nonfood approach 

488 with some similarities to that of the toxicology data requirements table for 

489 conventional pesticides to distinguish the use patterns that need more toxicity 

490 data from those that need less. The food-use column and the nonfood-use 

491 column are split into subcolumns to explain which food-uses or nonfood-uses 

492 require more data, and which require less. This modification of the food/nonfood 

493 approach delineates the specific data requirement needs for antimicrobial 

494 pesticides. 

495 For the final Residue Chemistry Data Requirements Table, EPA has 

496 adopted the commenters’ suggestion for a tiered format. After review of the 

497 commenter’s suggested tables, EPA believes the commenters’ suggested tiered 

498 approach is more suitable to antimicrobials than that proposed by EPA. 

499 vii. Change in terminology. The commenters’ asserted that the use of 

500 terms such as” high” or “low” as a means of tiering was insupportable, and an 

501 “unsubstantiated assignment of exposure categories” (ACC Comment in the docket 

502 at http://www.regulations.gov; document EPA-HQ-OPP-2008-0110-0088.1 p. 21 and 

503 22). EPA continues to believe that the use of “high” and “low” categories of 
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504 exposure defined by the antimicrobial use patterns are a valid method for identifying 

505 those exposures that have greater exposure and those that have less. Based on its 

506 experience, EPA understands which use patterns require more data. However, EPA 

507 can achieve the same result without the use of the terms “high” or “low.” Therefore, 

508 based on comments received, EPA notes that it is no longer using the terms “high 

509 human exposure” and “low human exposure” as table headers for the final 

510 Antimicrobial Toxicology Data Requirements Table. Similarly, EPA is no longer 

511 using the terms “high environmental exposure” and “low environmental exposure” 

512 as table headers for the final Antimicrobial Nontarget Organism, the Nontarget 

513 Plant Protection, or the Environmental Fate Data Requirements Table. However, 

514 EPA also notes that terms such as “high human exposure, “low human exposure, 

515 “high environmental exposure” and “low environmental exposure” can be 

516 appropriate when discussing a particular antimicrobial use. A statement that a 

517 particular use results in, for example, “high environmental exposure” provides 

518 information and alerts the reader that more data are likely to be needed, rather 

519 than less data. 

520 IV. Scope of the Rule 

521 This rule establishes a separate listing in Title 40 of the Code of Federal 

522 Regulations (CFR) for EPA’s data requirements under FIFRA and FFDCA section 

523 408 for antimicrobial pesticide uses. Although the rule is tailored to the unique 

524 characteristics of antimicrobial pesticides, it builds upon the existing data 

525 requirements imposed in 1984 on all pesticides and the 2007 amendments to 

526 those requirements pertaining to conventional pesticides. Both sets of data 

527 requirements – conventional and antimicrobial – are designed to provide EPA with 
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528 the information needed to make the required regulatory determinations under 

529 FIFRA and FFDCA section 408. FIFRA provides that a pesticide may not be 

530 registered for sale, distribution, and use unless “it will perform its intended function 

531 without unreasonable adverse effects on the environment . . . .” [7 U.S.C. 

532 136a(c)(5)(C)]. FIFRA defines “unreasonable adverse effects on the 

533 environment” as both “any unreasonable risk to man or the environment” and “a 

534 human dietary risk . . . inconsistent with the standard under section 408 of the 

535 [FFDCA]” [7 U.S.C. 136(bb)]. FFDCA section 408 directs that EPA shall not 

536 establish a tolerance permitting pesticide residues in food unless EPA determines 

537 that the tolerance is “safe” [21 U.S.C. 346a(b)(2)(A)(i)]. “Safe,” under FFDCA 

538 section 408, is defined as “a reasonable certainty that no harm will result from 

539 aggregate exposure to the pesticide chemical residue, including all anticipated 

540 dietary exposures and all other exposures for which there is reliable information” 

541 [21 U.S.C. 346a(b)(2)(A)(ii)]. In making safety determinations, EPA is required to 

542 consider aggregate and cumulative exposures from pesticides and other related 

543 substances and multiple factors specifically related to the protection of children 

544 [21 U.S.C. 346a(b)(2)(C) and (D)]. 

545 Under FIFRA, EPA has required “[s]ubstantial amounts of data on the 

546 pesticide, its composition, toxicity, potential human exposure, environmental 

547 properties, and ecological effects, as well as information on its product 

548 performance (efficacy) in certain cases” (73 FR 59384, October 8, 2008). Since 

549 1984, EPA has had codified FIFRA data requirements mandating data on, among 

550 other things, the toxicity hazards from ingestion of pesticides and exposure levels 
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551 of pesticide residues in food (Ref. 1). With the passage in 1996 of the Food 

552 Quality Protection Act, [Public Law 104-170, 110 Stat. 1489 (1996)], which added 

553 the expanded safety standard in FFDCA section 408 described above, EPA’s data 

554 needs have expanded. As noted in the preamble to the proposed rule, “[t]he 

555 combination of aggregate and cumulative exposure assessments required by 

556 FFDCA section 408 increases the nature and scope of EPA’s risk assessment, 

557 and potentially increases the types and amounts of data needed to determine that 

558 the FFDCA safety standard is met” (73 FR 59385, October 8, 2008). Moreover, 

559 with the explicit linkage in FIFRA between the FIFRA and FFDCA section 408 

560 safety standards (also added by FQPA), “[t]he data required to support a 

561 determination of ‘reasonable certainty of no harm’ under FFDCA are an integral 

562 part of the data needed for an ‘unreasonable adverse effects’ determination under 

563 FIFRA” [Id.; see 72 FR 60934 (October 26, 2007) (recodifying part 158 data 

564 requirements under the authority of both FIFRA and FFDCA section 408)]. This 

565 rule establishing specific data requirements for antimicrobial pesticides is 

566 designed to capture the broad range of data needed to assess the safety of 

567 pesticides under the standards of both FIFRA and FFDCA section 408. 

568 The ACC Biocides Panel and other commenters, however, have claimed 

569 that the scope of the proposed rule exceeds the EPA’s statutory authority 

570 because EPA is asserting “jurisdiction under FIFRA over some antimicrobial food 

571 uses where, in the Panel’s view, the statutory scheme provides exclusive jurisdiction 

572 to FDA” (Food and Drug Administration) (ACC Comment in the docket at 

573 http://www.regulations.gov; document EPA-HQ-OPP-2008-0110-0088.1 p. 31). 

574 Although the ACC Biocides Panel acknowledges that these uses are properly 
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575 regulated by EPA as “pesticides” under FIFRA, the Panel argues that “EPA’s 

576 responsibility for such use[s] is to evaluate whether the antimicrobial meets the 

577 standard for registration under FIFRA, taking into account FDA’s existing regulatory 

578 finding [under FFDCA section 409]. . . . EPA does not have the authority under 

579 either FIFRA or FFDCA to review or change the terms of the FDA approval.” (ACC 

580 Comment in the docket at http://www.regulations.gov; document EPA-HQ-OPP581 2008-0110-0088.1 p.33). In essence, the Panel is asserting that for these 

582 antimicrobial uses, EPA is without authority or jurisdiction under FIFRA to evaluate, or 

583 require data on, the level of risk from dietary exposure to the antimicrobial – where 

584 FDA has evaluated the safety of the use of the substance under section 409. As a 

585 basis for this argument, the ACC Biocides Panel points to the Antimicrobial 

586 Regulation Technical Corrections Act (ARTCA), [Public Law 105-324, in 1998], 

587 which divided FFDCA jurisdiction between EPA and FDA with respect to 

588 antimicrobials. The Panel further argues that EPA is wrong to rely on FIFRA 

589 section 2(bb)’s inclusion of the FFDCA section 408 safety standard in the 

590 definition of “unreasonable adverse effects” as authority for requiring data on 

591 antimicrobial uses falling under FDA’s FFDCA section 409 jurisdiction. Labeling 

592 EPA’s interpretation of FIFRA section 2(bb) in the proposed rule as “new,” the 

593 ACC Biocides Panel claims that EPA has contradicted its “long-standing” 

594 interpretation of this provision. 

595 The ACC Biocides Panel fundamentally misunderstands EPA’s statutory 

596 authority under FIFRA to require data pertaining to dietary risk from pesticides. 

597 EPA’s authority to regulate pesticides under FIFRA with regard to their dietary risk 

598 is derived from FIFRA not the FFDCA. Under FIFRA, EPA is charged with 
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599 protecting the public from “unreasonable adverse effects on the environment.” As 

600 noted above, FIFRA in section 2(bb) defines “unreasonable adverse effects” in the 

601 first instance as “any unreasonable risk to man . . . .” [7 U.S.C. 346(bb)]. This 

602 broad standard clearly encompasses any unreasonable dietary risk. EPA’s 

603 authority to regulate pesticides under FIFRA on the basis of dietary risk is 

604 explicitly reinforced by the second part of the unreasonable adverse effects 

605 standard which directs EPA to evaluate “human dietary risks” from “pesticides” 

606 under the safety standard in FFDCA section 408. [Id.] 

607 Nothing in FIFRA or the FFDCA limits or constrains EPA’s authority or 

608 jurisdiction to regulate pesticides based on dietary risk under FIFRA section 2(bb). 

609 The FIFRA section 2(bb) standard is independent from the safety standard under 

610 FFDCA section 409. Further, any finding by EPA under FIFRA that considers 

611 dietary risk would not “change the terms of a FDA approval;” rather, it would 

612 simply be a determination as to whether the separate FIFRA regulatory standard 

613 had been met. Finally, contrary to the ACC Biocides Panel’s contention, the 

614 adjustment by the ARTCA of EPA’s and FDA’s jurisdiction under FFDCA sections 

615 408 and 409 over antimicrobials does not affect EPA’s jurisdiction or authority with 

616 regard to dietary risks of pesticides under FIFRA. In fact, as explained below, not 

617 only did the ARTCA not amend FIFRA section 2(bb) but Congress in the ARTCA 

618 took the unusual step of expressly disavowing any intent to narrow the scope of 

619 EPA’s authority under FIFRA. 

620 The ARTCA was follow-on legislation to the major 1996 FFDCA 

621 amendments which, among other things, changed EPA and FDA jurisdiction 
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622 under FFDCA sections 408 and 409. Prior to 1996, section 408 of the FFDCA, 

623 which is administered by EPA, only applied to “pesticide chemicals” that were 

624 defined as FIFRA “pesticides” “used in the production, storage, and transportation 

625 of raw agricultural commodities” [21 U.S.C. 321(q) (1994)]. FIFRA pesticide 

626 residues in food not falling within this provision (i.e. FIFRA pesticides used later in 

627 the food production process than the growth of raw agricultural commodities) 

628 came under section 409 of the FFDCA as food additives [See 21 U.S.C. 321(s), 

629 348 (1994)]. FDA administers the establishment of food additive regulations 

630 under FFDCA section 409. Many antimicrobial pesticides used in conjunction with 

631 the manufacturing and processing of foods, at that time, were regulated as food 

632 additives. This division of legislative authority was changed by the FQPA in 1996. 

633 The FQPA amended the definition of “pesticide chemical” in the FFDCA to make it 

634 co-terminous with the definition of a “pesticide” in FIFRA by deleting the language 

635 restricting pesticide chemicals to those pesticides used in the production of raw 

636 agricultural commodities. Correspondingly, the FQPA also excluded “pesticide 

637 chemicals” from the definition of a “food additive” [Public Law 104-170 § 402, 110 

638 Stat. 1489, 1513 (1996)]. This change had the effect for FFDCA purposes of 

639 bringing all FIFRA pesticides under FFDCA section 408. Not only did Congress 

640 consolidate regulation of all pesticide residues in FFDCA section 408 but it also 

641 amended FIFRA to insure that the new safety standard in FFDCA section 408 

642 was part and parcel of the FIFRA registration standard for pesticides resulting in 

643 residues in food [7 U.S.C. 136(bb)(2)]. Specifically, as noted above, in section 

644 2(bb)(2), Congress defined an “unreasonable adverse effect on the environment” 
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645 under FIFRA as “a human dietary risk from residues that result from a use of a 

646 pesticide in or on any food inconsistent with the standard under section 408 of the 

647 Federal, Food, Drug, and Cosmetic Act [21 U.S.C. 346a].” 

648 In 1998 in the ARTCA, Congress modified slightly its FFDCA decision to 

649 consolidate all pesticide chemical residues in foods under FFDCA section 408. 

650 ARTCA amended the definition of “pesticide chemical” in FFDCA section 201 to 

651 exclude certain antimicrobial substances from the coverage of the definition [See 

652 21 U.S.C. 321(q)]. More specifically, with certain qualifications, the ARTCA 

653 excepted, from the definition of pesticide chemical, substances that are FIFRA 

654 pesticides and are “applied for [an antimicrobial] use on food, or the substance is 

655 included for such use in water that comes into contact with food, in the preparing, 

656 packing, or holding of the food for commercial purposes.” [21 U.S.C. 

657 321(q)(1)(B)(i)]. In addition, ARTCA excepted substances from the definition of 

658 pesticide chemical that are food contact substances, as defined in section 

659 409(h)(6) of the FFDCA, based on certain circumstances related to their use. 

660 These antimicrobial substances were now no longer considered “pesticide 

661 chemicals” under the FFDCA but fell under the definition of “food additive.” That 

662 had the effect of shifting the residues resulting from these antimicrobial 

663 substances from FFDCA section 408 to FFDCA section 409 and shifting agency 

664 jurisdiction under the FFDCA over the same from EPA to FDA. Importantly, 

665 Congress, in ARTCA, did not amend FIFRA to remove these uses of antimicrobial 

666 substances from the definition of “pesticide” under FIFRA and left unchanged 

667 FIFRA section 2(bb)(2) which mandates that the section 408 safety standard is 
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668 part of FIFRA’s unreasonable adverse effects standard as to FIFRA “pesticide” 

669 residues on food. Thus, EPA retained FIFRA jurisdiction over these antimicrobial 

670 substances (because they remained FIFRA “pesticides”) while FDA re-acquired 

671 FFDCA jurisdiction over them under FFDCA section 409 (because they were 

672 removed from the definition of “pesticide chemical”). To make clear its intent on 

673 EPA’s FIFRA jurisdiction, the ARTCA included the following express disavowal 

674 which was inserted into the FFDCA definition of “pesticide chemical:” 

675 With respect to the definition of the term ‘pesticide’ that is 

676 applicable to the Federal Insecticide, Fungicide, and 

677 Rodenticide Act, this clause [excluding certain 

678 antimicrobial substances from the FFDCA definition of 

679 “pesticide chemical”] does not exclude any substance 

680 from such definition” [21 U.S.C. 321(q)(1)(B)]. 

681 Since its passage, EPA has interpreted the ARTCA according to its plain 

682 language, excluding the designated antimicrobial substances from the coverage 

683 of FFDCA section 408 but continuing to regulate those antimicrobial substances 

684 that qualify as FIFRA “pesticides” under FIFRA and requiring that, when those 

685 antimicrobial pesticides result in residues in food, the risks from such residues be 

686 consistent with the safety standard in FFDCA section 408. After all, FIFRA 

687 section 2(bb)(2), on its face, applies to FIFRA “pesticides” and not FFDCA 

688 “pesticide chemicals.” Any other result would be directly contrary to Congress’ 

689 dictate that it was not excluding any substances from the FIFRA definition of 

690 “pesticide.” Accordingly, it is well within EPA’s FIFRA authority to require that 

691 data be submitted on pesticides to determine if those pesticides meet the FFDCA 

692 section 408 safety standard, whether or not those pesticides come within the 

693 definition of a FFDCA “pesticide chemical,” so long as the use of those pesticides 
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694 results in residues in food. On the other hand, the ACC Biocides Panel’s 

695 approach would involve amending the language of section 2(bb)(2) in a manner 

696 specifically rejected by the Congress when it passed ARTCA. 

697 There is no basis for the ACC Biocide Panel’s claim that EPA’s 

698 interpretation of FIFRA section 2(bb)(2) is “new.” The best evidence of the 

699 consistent and long-held nature of EPA’s interpretation are the numerous 

700 submissions to the Agency from the Panel (and others) over the last 10 years 

701 disputing EPA’s plain language approach to FIFRA section 2(bb)(2). (Refs. 2, 3, 

702 4, 5, 6, 7, 8, 9, and 10) 

703 V. Discussion of Several Issues Repeated Throughout Most Comments

704 In evaluating the comments received on proposed part 158, subpart W, 

705 EPA noted that four specific comments were routinely repeated throughout most 

706 of the entire set of comments. 

707 A. Differentiating the Review of Antimicrobials

708 1. Comment. EPA received several comments noting that FIFRA section 

709 3(h)(3)(A)(ii) specifies that EPA must differentiate the review of antimicrobial 

710 pesticides from that of other pesticides. 

711 2. EPA’s Response. FIFRA section 3(h)(3)(A)(ii) specifies, among other 

712 things, that, in proposed regulations to accelerate and improve the review of 

713 antimicrobial pesticide products, EPA shall define the various classes of 

714 antimicrobial use patterns, differentiate the types of review undertaken for 

715 antimicrobial pesticides, conform the degree and type of review to the risks and 

716 benefits presented by antimicrobial pesticides, and ensure that the registration 
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717 process is sufficient to maintain antimicrobial product efficacy. While those 

718 elements apply to a proposed rulemaking that the Agency published on 

719 September 17, 1999 (64 FR 50671), the Agency has been mindful of those same 

720 elements in its development of part 158, subpart W. As applied to antimicrobial 

721 product registration actions, differentiation refers to the tailoring of data 

722 requirements so that they are responsive to considerations about the antimicrobial 

723 products to which they relate. In practice, differentiation means that the data 

724 requirements applied to antimicrobials are designed to respond to the special or 

725 unique needs of antimicrobials such as the nature of the products, their 

726 ingredients, their uses, etc. Differentiation or tailoring does not mean that the 

727 resulting data requirements for antimicrobials will necessarily be comprised of 

728 more, less, or the same number and type of data requirements as required for 

729 other types of pesticides such as conventional pesticides. 

730 For example, the residue chemistry data requirements for conventional 

731 pesticides focus on the application of agricultural pesticides to crops growing in 

732 the fields. However, the residue chemistry data requirements for antimicrobials, 

733 codified today, have been tiered to account for applications that focus not on 

734 crops growing in the fields (where antimicrobials are rarely used), but instead 

735 account for antimicrobial uses, including those that result in residues on food 

736 more indirectly, such as from use as sanitizers in food processing plants. The 

737 overall impact is to require fewer studies since the tiering used for the 

738 antimicrobial residue chemistry data requirements table is structured differently, 

739 and there are fewer “R” studies and most studies are “CR.” However, there are 
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740 two residue chemistry data requirements (migration and nature of the residue on 

741 surfaces) for antimicrobials that are not included in the conventional residue 

742 chemistry data requirements table because they reflect the unique use sites for 

743 antimicrobials; see Unit XVI for additional discussion. Ecotoxicity and 

744 environmental fate data requirements provide another example of the 

745 differentiation of data requirements between antimicrobials and conventional 

746 pesticides. While conventional or biochemical/microbial pesticides are often used 

747 outdoors, and are deliberately placed/spread in the environment, most 

748 antimicrobials are used indoors. As discussed in the preamble (73 FR 59406), 

749 previously EPA had assumed that many of the indoor uses went down-the-drain 

750 to a waste water treatment plant (WWTP), where the WWTP processes would 

751 mitigate environmental concerns. Therefore, in 1984, EPA required basic 

752 ecotoxicity and environmental fate data for conventional pesticides but made 

753 these types of data conditional for indoor uses such as antimicrobials based on 

754 whether antimicrobial-specific data indicated that environmental exposure may 

755 occur. However, as discussed in the proposed rule (73 FR 59407), in recent 

756 years there have been detections of antimicrobial chemicals (with indoor uses) in 

757 waterbodies. These antimicrobials are moving into the environment via treated 

758 effluent. Therefore, EPA is requiring for antimicrobials a specific tiered-set of data 

759 to evaluate the likelihood of environmental exposure to antimicrobials that may 

760 reach a WWTP, as a result of being washed down the drain via leachates, 

761 rinsates, and flushes. These data evaluate whether antimicrobials are likely to 

762 survive the treatment processes at a typical WWTP, and thus would be present in 
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763 the WWTP effluent. Antimicrobials that do survive the treatment processes have 

764 the potential to end-up in the terrestrial or aquatic environments and higher-tiered 

765 ecotoxicity and environmental fate data are only triggered for these antimicrobials. 

766 

767 Thus, differences in data requirements stem directly from the inherent 

768 differences in the nature of the particular type of pesticide's use. Even with such 

769 differentiation or tailoring, there is a general core of data requirements which may 

770 be expected to be applicable to any kind of pesticide product, such as product 

771 chemistry data requirements. EPA’s ultimate goal with its antimicrobial data 

772 requirements is to create a body of data requirements which produce sufficient 

773 information for Agency to consider and use in making its statutorily-required 

774 determinations regarding the risks and benefits, where applicable, of antimicrobial 

775 pesticides. The differentiation or tailoring of the antimicrobial data requirements is 

776 instrumental in accomplishing that goal. 

777 B. Rewrite and Repropose the Rule

778 Several commenters requested that EPA rewrite and then repropose this 

779 rule. Commenters raised three arguments as to why EPA should repropose. 

780 First, the proposed regulation does not contain scientifically-based criteria for 

781 determining data requirements but instead requires that data requirements be 

782 determined in case-by-case consultations in which EPA retains “sole discretion” 

783 as to the data required. Second, EPA has not disclosed how it plans to use the 

784 proposed data in EPA risk assessments. Third, affected parties cannot properly 

785 evaluate the data requirements without final guidelines on how such studies 
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786 should be conducted. Each of these three arguments are addressed in detail 

787 below. 

788 1. Comment on scientifically-based criteria. Several commenters focused 

789 on the testnotes to the data requirements tables, and claimed that the proposed 

790 rule “leaves too many standards and decisions to the sole discretion of EPA, 

791 creating uncertainty and, inevitability, inconsistency in regulatory decision 

792 making.” Too many determinations, the commenter asserted, are at “EPA’s 

793 discretion” because the proposal is vague without clear-cut criteria. Additionally, 

794 they argued that there are too many places in the test notes where consultation 

795 with the Agency is required or the phrase “as determined by the Agency” is used. 

796 (One commenter listed 37 instances in which the proposal allegedly substituted a 

797 mandatory consultation process for regulatory criteria.) According to the 

798 commenters, EPA should eliminate most of the consultation requirements and 

799 instead, repropose the rule providing a clear set of requirements. 

800 2. EPA’s response to comment on scientifically-based criteria. Test notes 

801 often contain qualitative or quantitative measures for use in determining whether a 

802 study is triggered or not. Most frequently this occurs when there is an initial study 

803 that relates to whether subsequent testing would be needed or not. Not all 

804 triggers are easily reduceable to quantitative measures and EPA believes that 

805 qualitative descriptors such as “expected to enter the environment in significant 

806 concentrations,” “if repeated dermal exposure is likely to occur under conditions 

807 of use,” and “the use of the pesticide is likely to result in repeated human 

808 exposure over a limited portion of the human lifespan” provide meaningful criteria 
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809 for determining when a study is triggered. EPA has carefully reviewed each of the 

810 37 test notes cited by one commenter and has identified several instances in 

811 which clarification of the criteria was appropriate. EPA’s analysis of these 37 test 

812 notes and resultant changes are included in response to comment 3 in the 

813 Response to Comments Document in the docket at http://www.regulations.gov. 

814 In numerous places the test notes contain language stating that the criteria 

815 would be applied “as determined by the Agency.” Commenters have 

816 misinterpreted this as giving EPA the authority to make decisions on factors other 

817 than the regulatory criteria included or in its “sole discretion.” This was not EPA’s 

818 intent and, accordingly, EPA has removed all “as determined by the Agency” from 

819 all test notes for the final antimicrobials rule so there can be no chance of a 

820 misunderstanding of how the criteria are to be applied. 

821 Commenters also asserted that the EPA’s alleged mandatory consultation 

822 requirements rendered the test notes meaningless, as EPA would determine 

823 whether studies were required in private based on unspecified factors. EPA 

824 disagrees. The commenters have misread the proposed rule language and 

825 misunderstood the purpose for consultation. The consultation references were 

826 not intended to impose a mandatory consultation requirement. To the contrary, 

827 the references to consultation was an attempt by EPA to signal its willingness to 

828 meet with applicants to adapt studies, if necessary, to the specifics of individual 

829 antimicrobials. 

830 Consultation is a longstanding, commonly used and valuable process in 

831 EPA’s Pesticide Program. Applicants often meet with OPP staff on a pre-
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832 submission basis to review and discuss the adequacy of the available data. OPP 

833 believes that such meetings are beneficial to both EPA and the applicants. In 

834 practice, such meetings are very often sought by registrants and applicants. By 

835 encouraging communication and exchange of ideas, such discussions can help in 

836 the development of clearer expectations of what must be submitted in instances 

837 where data requirements involve complexities. Consultation can result in data 

838 that better meets EPA’s needs and saves resources for both EPA and the 

839 applicant. Depending upon what is intended to be addressed, such meetings do 

840 not necessarily need to be held in person, but can be frequently accomplished via 

841 tele-conferencing. 

842 EPA did not intend its references to consultations in the test notes to 

843 impose mandatory consultation requirements; neither did EPA intend the 

844 consultation references as a means of establishing a different standard for 

845 determining if a study is triggered. EPA has carefully reviewed all test notes in the 

846 antimicrobials final rule and removed all references to consultation from all 

847 testnotes for the antimicrobials rule so there can be no chance of 

848 misunderstanding the voluntary nature of consultation. 

849 3. Comment on use of data in risk assessment. The commenters also 

850 argued that reproposal was necessary because they could not meaningfully 

851 comment on the proposal without understanding how the data would be used by 

852 EPA. Specifically, one commenter wrote: “It is not plausible for [the commenter] 

853 or others to meaningfully comment on the Proposal without the benefit of 

854 understanding the risk assessment approaches EPA plans to use, (e.g., human 
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855 and ecological), the ways in which the data requirements will provide information 

856 to conduct those assessments and the ways EPA will use those risk assessments 

857 in making regulatory decisions. 

858 4. EPA’s response on use of data in risk assessment. EPA disagrees with 

859 this comment for several reasons. First, how EPA conducts risk assessments and 

860 how it uses toxicological, ecological, and exposure data in those risk assessments 

861 is well known. Risk assessment is not unique to OPP. The principles used by 

862 OPP and, in fact, by EPA are those used by the scientific community in general. 

863 OPP follows the processes and procedures in the many risk assessment 

864 guidance documents that have been issued by EPA (see 

865 http://www.epa.gov/riskassessment/guidance.htm). The Agency’s exposure and 

866 risk assessment procedures have been presented in numerous exposure and risk 

867 assessments for antimicrobial pesticides. EPA’s assessments reflect the best

868 available data, and the state of the science of exposure and risk assessment 

869 models, methods, and procedures. 

870 Moreover, OPP’s risk assessment procedures for pesticides are well871 documented. EPA has recently concluded the process of completing 

872 Reregistration Eligibility Decision Documents for all pesticides under FIFRA and 

873 reassessing all FFDCA pesticide tolerances. This was a very open process 

874 involving multiple public comment opportunities as to each pesticide. Further, all 

875 regulatory decision documents as well as the underlying risk assessments have 

876 been made available to the public. EPA has now begun new pesticide reviews 
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877 under the Registration Review program, and that process is equally open and 

878 transparent. 

879 A second reason why EPA believes this comment to be misdirected is that 

880 the proposed rule does not represent a change to EPA’s existing and transparent 

881 risk assessment procedures. Rather, the proposal is merely designed to tailor the 

882 existing data requirements that apply to all pesticides in a way that is more 

883 specific to antimicrobial pesticides, as well as including some new requirements 

884 applicable to antimicrobials. 

885 Finally, the comment is without foundation because EPA has explained the 

886 need for each study and provided background information on the purpose for 

887 which each study would be required. Part 158, subpart B contains an extensive 

888 description of the need for and use of submitted studies (40 CFR 158.130). 

889 Additionally, as explained in the preamble to the antimicrobials proposed rule, 

890 EPA relied on the proposed and final rules for establishing data requirements for 

891 conventional pesticides. As stated in the proposed rule for antimicrobials, the 

892 rationales for requiring and/or revising particular data requirements were in those 

893 rules. 

894 With few exceptions, these rationales are also 

895 applicable to antimicrobial pesticide chemicals, and 

896 as such have not been repeated in today’s proposed 

897 rule. Today’s proposal discusses in detail only those 

898 revisions that are singularly applicable to antimicrobial 

899 pesticides, including antifoulants and wood 

900 preservatives.” (73 FR 59384) 

901 
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902 Examples of studies applicable to antimicrobial pesticides and for which a 

903 description of the need for the requirement was included in the preamble to the 

904 proposed rule for antimicrobials include the need for: 

905  The 90-day dermal and 90-day inhalation studies for a heating, 

906 ventilation, air conditioning, and refrigeration uses ( 73 FR 59395), 

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

908  Environmental fate studies to support a down-the-drain assessment 

909 (73 FR 59408). 

910 One commenter presented several examples of what the commenter 

911 labeled as EPA’s “ad hoc risk assessment processes.” An examination of those 

912 examples shows that the commenter is concerned with what it labels as 

913 “inconsistency in EPA’s current practice” as to when a dietary risk assessment is 

914 needed for antimicrobial pesticides. The commenter argued that this alleged 

915 inconsistent practice shows the “need for stable, transparent guidance on risk 

916 assessment to support data requirements regulation.” EPA does not believe that 

917 it has been inconsistent in its risk assessments. Furthermore, EPA does not 

918 believe that such “inconsistencies,” if they exist, would mean that affected parties 

919 could not comment meaningfully on the proposed data requirements. Ultimately, 

920 the issue with the data requirements rule is whether EPA has asked for data 

921 needed for determining whether pesticides meet the relevant statutory safety 

922 standards. The fact that EPA might have been inconsistent in the past in its 

923 determinations with regard to the safety standard or how it went about assessing 

924 whether a pesticide met the safety standards (e.g., did EPA need to do a dietary 
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925 risk assessment), does not handicap an affected party in determining whether a 

926 proposed data requirement is consistent with the statutory safety standards. To 

927 reiterate, the relevant question is not whether EPA has guidance on when dietary 

928 risk assessment is needed but whether the proposed data requirements 

929 pertaining to dietary risk would require information that are appropriate to EPA’s 

930 determination under the applicable statutory safety standards. To the extent, the 

931 commenter is concerned with any particular Agency decision regarding when a 

932 dietary risk assessment is needed for antimicrobials, EPA encourages the 

933 commenter to raise that concern directly with the Agency in the context of the 

934 specific matter causing the commenter concern. 

935 This commenter later filed additional comments that further developed the 

936 argument that reproposal is necessary because EPA allegedly has not clearly 

937 defined when a dietary risk assessment is needed. The commenter wrote: “[T]he 

938 Proposal does not clearly articulate any standards for determining what uses 

939 triggers a food analysis. It has become apparent since the Proposal was issued 

940 that the Agency will interpret this regulation to vastly increase the number of 

941 antimicrobials regulated as food use.” (ACC/CSPA letter in the docket at 

942 http://www.regulations.gov; document EPA-HQ-OPP.2008-0110-0107, p. 2). 

943 Further, the commenter then asserts that “EPA’s economic analysis does not 

944 even attempt to address the increase in the burden on registrants and applicants 

945 that this [alleged] expansion of the need for ‘food contact’ approvals will cause.” 

946 (Id.) These additional comments suggest that this commenter is concerned with 

947 EPA decisions issued prior to today’s final rule (and, in most cases, prior to 
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948 issuance of the proposed rule) and fears how the final rule may be interpreted in 

949 the future. However, it is difficult to determine from these comments whether the 

950 commenter is claiming that this alleged “expansion” of food use antimicrobials is 

951 effected by any particular language in the proposed rule. To the extent the 

952 commenter is arguing that the expansion is caused by EPA’s application of the 

953 FFDCA section 408 standard to all antimicrobial food uses under FIFRA section 

954 2(bb) (whether the use requires clearance under FFDCA section 408 or 409), the 

955 commenter, as explained in Unit XVI.A, misunderstands EPA’s authority under 

956 FIFRA and EPA’s practice as to antimicrobials since the passage of ARTCA. In 

957 another place in its recently-filed comments, the commenter argues that the use 

958 of the categories of “direct food use” and “indirect food use” “create the potential 

959 for almost all antimicrobials to be considered as possibly leaving residues on 

960 food.” (ACC attachment 1 in the docket at http://www.regulations.gov; document 

961 EPA-HQ-OPP.2008-0110-0108, p. 4) However, EPA adopted the categories of 

962 direct and indirect food use as a way to tier data requirements for residue 

963 chemistry and toxicology, not to expand the category of food uses. For a use to 

964 qualify as an indirect food use it must result in residues in food and EPA clearly 

965 has the authority under FIFRA and the FFDCA to request data on and assess the 

966 risk of pesticide residues in food. Despite the commenter’s claims to the 

967 contrary, it is not EPA’s intent to use this data requirements rule as a basis for 

968 expanding what antimicrobial uses qualify as direct or indirect food uses. 

969 Accordingly, EPA’s economic analysis has accurately captured the costs imposed 

970 by this rule. 
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971 5. Comment on lack of final guidelines. Finally, commenters argued that 

972 reproposal was needed because affected parties cannot properly evaluate the 

973 data requirements without final guidelines on how such studies should be 

974 conducted. 

975 6. EPA’s Response on lack of final guidelines. EPA disagrees with this 

976 comment: EPA can require submission of a particular study even if no guideline 

977 has been provided. The types of data needed for EPA to make a registration 

978 decision are clearly identified in its proposed rule. Testing laboratories routinely 

979 conduct these studies, as evidenced by the test cost data which was available for 

980 use in both EPA’s and the commenter’s economic analyses. Final guidelines are 

981 available for the majority of tests required, and draft guidelines provide information 

982 for the applicant to consider. Since there was an understanding of the types of 

983 data EPA proposed to require, the commenter had sufficient information to 

984 comment on whether EPA had asked for the data needed for determining whether 

985 pesticides meet the relevant statutory safety standards. 

986 It is important to keep in mind that, as noted in the proposed rule, new part 

987 158, subpart W is “retaining most current data requirements for antimicrobials. . . 

988 and revises other existing data requirements.” (73 FR 59383) The guidelines that 

989 the commenter asserts as not providing sufficient information to permit meaningful 

990 comment pertain, for the most part, to these existing data requirements that are 

991 not being modified by this rulemaking. As to the “new” data requirements that are 

992 imposed by this rule, the commenter has not specifically explained why interested 

993 parties cannot meaningfully comment on these requirements or why a final 
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994 guideline is needed to provide meaningful comments on these studies. In fact, as 

995 to these “new” studies, OPPTS guidelines are available for all except the nature of 

996 the residue on surfaces study. For that study, due to the many site- and chemical 

997 specific variations, a protocol review is required. 

998 This commenter later filed additional comments stating that “FIFRA 

999 requires EPA to issue test guidelines.” (ACC/CSPA letter in the docket at 

1000 http://www.regulations.gov; document EPA-HQ-OPP.2008-0110-0107, p. 4). In 

1001 accordance with FIFRA section 3(c)(2)(A), EPA has promulgated data 

1002 requirement rules “specifying the kinds of information which will be required to 

1003 support the registration of a pesticide.” EPA is not required to issue guidance 

1004 explaining how studies that are addressing the data required under the 

1005 regulations should be performed. Additional information on EPA’s development of 

1006 guidelines is in Unit XX. 

1007 C. Alternative Testing Paradigms. 

1008 1. Comment. A commenter asked how OPP plans to implement the 

National Academy of Sciences (NAS)/EPA Vision of Toxicity Testing in the 21st 1009 

1010 Century or the Strategic Plan for Evaluating the Toxicity of Chemicals. The 

1011 commenter noted that the rule should be specific in identifying alternative 

1012 approaches that EPA will consider. 

1013 2. EPA’s Response. In the proposed rule, in Unit XVIII, entitled “Alternative 

1014 Testing Paradigms,” EPA discussed its commitment to moving towards a more 

1015 efficient and refined testing/risk assessment paradigm for antimicrobial pesticide 

1016 chemicals. That discussion included the following: 
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1017  OPP’s current thinking on how Structure-Activity-Relationships (SAR) 

1018 and Quantitative SAR (QSAR or (Q)SAR) modeling could be used as part of an 

1019 integrated approach to hazard and risk assessment to support a regulatory 

1020 decision-making process for antimicrobial pesticides. 

1021  The evolution of the current paradigm of animal (in vivo) toxicity 

1022 testing toward a more integrated tiered testing approach for antimicrobial 

1023 pesticides. 

1024  Development of computational tools for interpreting data from 

1025 computational chemistry, high-throughput screening (HTS) and genomic 

1026 technologies. 

1027  The EPA-funded reports by the NAS entitled “Toxicity Testing for 

Assessment of Environmental Agents” (2006) and “Toxicity Testing in the 21st 1028 

1029 Century: A Vision and a Strategy” (2007). 

1030 The NAS recommendations are truly visionary and involve a transformative 

1031 paradigm shift in toxicology based largely on the increased use of in vitro

1032 molecular and cellular assays, and computational modeling that make testing 

1033 faster and less costly, and reduces animal testing significantly. The new 

1034 technologies are expected to help EPA better understand how chemicals perturb 

1035 normal biological function(s), and thus identify toxicity pathways. Potential toxic 

1036 effects of chemicals could then be predicted based on in vitro bioactivity profiles 

1037 derived from a chemical’s effects on cellular molecules and processes. Thus, the 

1038 scientific foundation for this new paradigm is based on linking in vitro effects with 

1039 adverse outcomes in vivo, and on computer modeling that extrapolates to 
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1040 predicted responses in whole tissues, organisms and populations based on 

1041 realistic human or environmental exposures. 

1042 EPA is working to develop and evaluate new technologies in molecular, 

1043 cellular, and computational sciences to supplement or replace the more traditional 

1044 methods of toxicity testing and risk assessment (see 

1045 http://www.epa.gov/pesticides/science/testing-assessment.html). Such an 

1046 approach begins with consideration of exposure information along with hazard1047 based hypotheses about the plausible toxicological potential of a chemical or 

1048 group of chemicals based on their physical-chemical properties and their effects 

1049 on biological targets in vitro. This information is then combined with computer 

1050 modeling to target animal testing to the specific data needed for human health 

1051 and ecological risk assessments. 

1052 No single new technology will be able to address all situations. However, 

1053 by using a suite of tools and approaches in combination, EPA believes it is 

1054 possible to improve the hazard and exposure assessments that form the basis for 

1055 understanding pesticide chemical risks. It will take time and substantial research 

1056 to build this new approach. OPP will incorporate the new technologies into EPA’s 

1057 hazard and risk assessment processes as the technologies are sufficiently 

1058 developed and peer reviewed. Development and vetting of this new approach to 

1059 chemical management must be accomplished while continuing to make pesticide 

1060 registration decisions. Eventually, the new technologies should: 

1061  Create a broader suite of computer-aided methods to better predict 

1062 potential hazards and exposures, and to focus testing on likely risks of concern. 
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1063  Improve the approaches to more traditional toxicity tests to minimize 

1064 the number of animals used while expanding the amount of information obtained. 

1065  Improve OPP’s understanding of toxicity pathways to allow 

1066 development of non-animal tests that better predict how exposures relate to 

1067 adverse effects. 

1068  Improve the diagnostic biomonitoring and surveillance methods to 

1069 detect chemical exposures and identify causes of toxic effects. 

1070 Since the publication of the proposed rule in October 2008, OPP 

1071 announced its strategic direction to move toward an improved testing and 

1072 assessment paradigm where in vivo (animal) testing would be targeted to the 

1073 most likely hazards of concern. OPP envisions an enhanced testing/assessment 

1074 paradigm that is a progressive, tiered-testing approach. This paradigm shift 

1075 should accrue the following benefits to OPP: 

1076  Ability to evaluate more chemicals across a broader range of 

1077 potential effects in a shorter time frame. 

1078  Potential to increase the feasibility of assessing the risks posed by 

1079 mixtures. 

1080  Enhanced predictive ability to determine whether animal testing is 

1081 needed to refine a risk assessment and to inform management decisions. 

1082  Refine and reduce animal testing by maximizing information 

1083 obtained from animal studies, and focusing on effects of concern. 

1084  Opportunities for improved diagnostic biomonitoring and surveillance 

1085 methods to detect chemical exposures and identify causes of toxic effects. 
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1086  Enhance the quality and efficiency of risk assessment and risk 

1087 management decisions. 

1088 Over the next several years, OPP intends to improve and transform its 

1089 approach to pesticide risk management by enhancing its ability to use integrated 

1090 approaches to testing and assessment. The Agency’s work on an integrated 

1091 approach means the development of increasingly effective laboratory animal tests 

1092 that are designed to maximize the information generated about the nature of the 

1093 effects being studied. OPP intends to expand its toolbox of predictive models. 

1094 The new toxicity and exposure approaches will enhance priority-setting and 

1095 screening approaches and therefore focus Agency and societal resources on 

1096 those chemicals with the greatest risk potential. 

1097 These advances will be incorporated within a risk assessment framework 

1098 of problem formulation, hazard, dose response, exposure assessment, and risk 

1099 characterization to support pesticide registration decisions. As this framework 

1100 evolves, EPA will create pilot programs and develop guidance documents to 

1101 inform applicants and others of the alternative approaches being used. 

1102 It will require many years to realize the NAS vision of a new toxicity 

1103 paradigm based on evaluating perturbations in cellular pathways by reliance on 

1104 an array of computational and in vitro methods. However, the development and 

1105 expansion of certain tools used to guide more intelligent in vivo testing is 

1106 anticipated to become available in the nearer term (≤5 years) which includes 

1107 (Q)SAR/expert systems, TTCs, and in vitro technologies. As EPA transitions to 

1108 the use of these components of intelligent testing or alternative methods, 
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1109 communication will be essential. Through its Pesticide Program Dialog 

Committee, OPP has created a 21st 1110 Century Toxicology/New Integrated Testing 

1111 Strategies Workgroup. For information, see 

1112 http://www.epa.gov/pesticides/ppdc/testing/index.html. 

1113 Additionally, OPP has and will continue to publicly vet this new approach. 

1114 On May 24 – 26, 2011, OPP requested that the FIFRA Scientific Advisory Panel 

1115 (SAP) consider and revise a set of scientific issues related to Integrated 

1116 Approaches to Testing and Assessment (IATA) Strategies: Use of new 

1117 computational and molecular tools. OPP plans to build on an established 

1118 foundation of using a variety of tools in a tiered testing and assessment 

1119 framework by systematically adding new tools and methodologies, as well as an 

1120 advancing understanding of key events in toxicity pathways. OPP requested the 

1121 SAP's input on EPA’s plans to maximize use of existing data from similar 

1122 compounds, including information from new toxicity hazard computational and in 

1123 vitro predictive models, and exposure modeling to target in vivo toxicity testing 

1124 that is necessary to assess and manage chemical risks, appropriately. Two case 

1125 studies illustrated the use of these approaches. The SAP Report, once 

1126 completed, will be available at 

1127 http://www.epa.gov/scipoly/sap/meetings/2011/052411meeting.html#frn.

1128 VI. Discussion of Key Comments on Antimicrobial Use Patterns

1129 A. Definitions of Use Patterns 

1130 1. Comment. The commenter suggested different use patterns for EPA to 

1131 consider. The commenter believes that the use patterns proposed by EPA are not 
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1132 use patterns but descriptions of product types. The commenter suggested six 

1133 general use patterns for EPA to consider. These include: 

1134  Indoor industrial (all nonfood); 

1135  Indoor residential/commercial/institutional nonfood; 

1136  Indoor commercial/institutional food; 

1137  Aquatic areas nonfood; 

1138  Aquatic areas food; 

1139  Material preservative for exempt treated article uses. 

1140 2. EPA’s Response. The Agency disagrees that these suggested use 

1141 patterns are adequate substitutes for the proposed use patterns. The use 

1142 patterns that EPA proposed provide a reasonable approach for allowing the 

1143 Agency to more clearly identify and tailor the data requirements for the different 

1144 type of antimicrobial pesticides. In some cases, that is best accomplished by 

1145 using the product type to define the use pattern. 

1146 EPA has reviewed the commenters’ descriptions of their six suggested 

1147 general use patterns and has determined that they do not acknowledge all 

1148 potential exposure pathways of antimicrobial pesticides, particularly those 

1149 discharged to wastewater as a result of processing and end-use. Although three 

1150 of the proposed general use patterns include “indoor” in the name, the exposure 

1151 potential for these use patterns is not limited to the indoor environment. This is 

1152 because these patterns include processes and end-uses of antimicrobial 

1153 pesticides that are discharged to wastewater, thereby leading to the potential for 

1154 microorganisms in WWTPs to be exposed to antimicrobial pesticides and for 
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1155 aquatic organisms to be exposed to antimicrobial pesticides in surface water 

1156 downstream of WWTPs. If the antimicrobial is not completely removed during 

1157 treatment, exposures of humans to antimicrobials may also be associated with 

1158 antimicrobials discharged to wastewater that enters WWTPs and subsequently 

1159 enters surface water via WWTP effluents. Furthermore, there may also be the 

1160 potential for terrestrial organisms and humans to be exposed to antimicrobial 

1161 pesticides if the antimicrobial that is discharged to wastewater partitions to 

1162 biosolids. 

1163 Since the processing or end-use of an antimicrobial pesticide in an indoor 

1164 setting does not preclude the potential for its release to ambient environmental 

1165 media, particularly under circumstances in which there is potential for discharges 

1166 of antimicrobial pesticides to wastewater, EPA believes that the designation of an 

1167 antimicrobial use patterns as “indoor” is misleading. Based on the conclusion that 

1168 processing or end-use of an antimicrobial pesticide in an indoor setting does not 

1169 preclude its release to the ambient environment, EPA believes that a down-the1170 drain analysis is needed for all use patterns with the exception of the aquatic 

1171 areas use pattern. 

1172 The commenter’s suggested use patterns are also inconsistent with EPA’s 

1173 reevaluation of the data required for wood preservatives. In response to 

1174 comments, the Agency determined that all treated wood needs to be considered 

1175 as having the potential to come into contact with surface water. Therefore, for 

1176 wood preservatives, EPA has changed several data requirements in both the 

1177 environmental fate table and the non-target organisms table from “CR” to “R.” 
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1178 However, under the commenter’s six suggested use patterns, wood preservatives 

1179 would be considered to be the same as material preservatives: The commenter 

1180 did not differentiate the data needed between the two use patterns. EPA believes 

1181 that the data needed for a wood preservative is distinctly different from that 

1182 needed for a materials preservative. Wood preservatives have a high potential for 

1183 environmental exposure, as evidenced by both environmental fate and nontarget 

1184 organisms data requirements that are “R.” Material preservatives have a lower 

1185 potential for environmental exposure and consequently are “CR.” Thus, the data 

1186 requirements codified today acknowledge the differences in the data needed by 

1187 having two distinctly different use patterns: wood preservatives and material 

1188 preservatives. 

1189 Given the inclusion of the term “indoor” as part of the title of three of the 

1190 suggested use patterns, and the combining of wood preservatives and materials 

1191 preservatives into a single use pattern, EPA believes that the six general use 

1192 patterns suggested by the commenter (see above) would not adequately serve 

1193 EPA’s or the public’s needs. Additionally, the 1997 review by the FIFRA Scientific 

1194 Advisory Panel (SAP) of EPA’s 12 antimicrobial use patterns indicated the SAP’s 

1195 agreement that the Agency’s proposed designation of 12 use patterns was a 

1196 reasonable approach to organizing data requirements, and was, in fact, similar to 

1197 the approaches used by Canada’s Pest Management Regulatory Agency 

1198 (PMRA), and the California EPA. Therefore, EPA is codifying the 12 use patterns 

1199 that were proposed. 

1200 B. Wood Preservative Use Pattern
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1201 1. Comment. Several commenters questioned how wood preservatives 

1202 were treated in the proposed rule. One commenter thought that all wood 

1203 preservatives should be considered as having contact with water. Another 

1204 commenter argued that the industrial, commercial and do-it-yourself uses of wood 

1205 preservatives are different and should be assessed differently. 

1206 2. EPA’s Response. Wood preservatives are pesticides for incorporation 

1207 into wood products to control wood degradation problems due to fungal rot or 

1208 decay, sapstain, molds, or wood-destroying insects. 

1209 As explained in the proposed rule, (73 FR 59405) EPA’s current practice of 

1210 determining the data required for a wood preservative product is dependent upon 

1211 where the product is intended to be used (land-only versus land and aquatic). 

1212 Under this approach, fewer environmental fate and ecological effects studies are 

1213 required for products that limit their use patterns to land-only uses. This approach 

1214 also assumes that diversion does not occur and that wood that is treated for land1215 only uses does not end up in the water and vice versa. EPA specifically 

1216 requested comments on the regulation of wood preservative products, and 

1217 indicated that based on the comments received could determine to continue with 

1218 the current practice of considering land-only applications, or change to a land and 

1219 aquatic usage. Based on comments indicating that the data required to register a 

1220 wood preservative should not differentiate between land only and aquatic only 

1221 applications of treated wood, EPA has re-evaluated this approach. As discussed 

1222 in the proposed rule, it is difficult to assure that diversion does not occur. EPA 

1223 considered three possibilities: 
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1224  Assume all treated wood could have the potential to come into contact 

1225 with surface water. 

1226  Use an approach similar to that advocated by the American Wood 

1227 Protection Association (AWPA) approach which differentiates between 

1228 marine/freshwater and ground contact use/above ground contact use. 

1229  Maintain status-quo. 

1230 Wood preservatives used to protect wood structures placed directly in or over 

1231 water (e.g., marine pilings, docks) will leach active ingredient into the water, 

1232 resulting in potential exposure of aquatic organisms. Wood preservatives used in 

1233 the terrestrial environment for uses such as fences, siding, and decks will leach 

1234 active ingredient into soil where it may be transported into the aquatic 

1235 environment and expose aquatic organisms. 

1236 The Emission Scenario Document (ESD) for Wood Preservatives prepared 

1237 by the Organization for Economic Co-operation and Development (OECD) as part 

1238 of its Series on Emissions Scenario Documents provides guidance on how to 

1239 estimate emissions of chemical substances in wood preservative products to air, 

1240 water, and soil as a result both of product application and storage of treated wood 

1241 prior to shipment and treated wood-in-service. This OECD ESD documents the 

1242 occurrence of pathways of release of chemical substances during wood 

1243 preservative application to facility drains that subsequently convey wastewater to 

1244 WWTPs; entry of chemical substances to adjacent surface water bodies by way of 

1245 run-off water from unpaved storage of wood preservative-treated products 

1246 following a rain event; and leaching of chemical substances from in-service uses 
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1247 of treated exterior wood out of ground (i.e., fences, noise barriers), wood in1248 ground (transmission poles, fence posts), and wood in direct contact with fresh 

1249 and sea water (poles and planks/decking of jetties and wharfs). Additional 

1250 information on indirect releases to surface water of antimicrobial pesticides used 

1251 as wood preservatives can be found in response to comment 134.1 in the 

1252 Response to Comments Document in the docket at http://www.regulations.gov. 

1253 Given the number of pathways identified, that result in potential exposure 

1254 from treated wood, the Agency determined that all treated wood should be 

1255 considered as having the potential to come into contact with surface water. All 

1256 wood preservative risk assessments will now be performed considering that the 

1257 treated wood could end-up either on the land or in the aquatic environment. As 

1258 previously discussed, there are multiple pathways for wood preservative 

1259 degradates and/or leachates to reach surface water. The AWPA approach would 

1260 have continued the practice of determining the data requirements based on the 

1261 intended use site of the treated product. 

1262 Given this decision, that all treated wood could have the potential to come 

1263 into contact with surface water, the wood preservative columns of the final 

1264 Environmental Fate and the Nontarget Organisms Tables were revised. 

1265 For the final Environmental Fate Table, for the wood preservatives column, 

1266 the data requirements for anaerobic soil metabolism, aerobic aquatic metabolism, 

1267 and anaerobic aquatic metabolism were changed from “CR” to “R.” Because 

1268 treated wood products have outdoor usages, the Agency believes that these 

1269 products have the potential to come into contact with surface water as well as 
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1270 soils which can become flooded or waterlogged and then be released to surface 

1271 water. 

1272 For the final Nontarget Organism Table, for the wood preservatives 

1273 column, the data requirements for chronic toxicity testing with fish (fish early-life 

1274 stage) and aquatic invertebrate (aquatic invertebrate life-cycle) are being changed 

1275 from “CR” to “R” to provide chronic data when chronic exposure is expected. 

1276 The Agency agrees that the industrial, commercial and do-it-yourself uses 

1277 of wood preservatives are different in terms of human exposure. Industrial wood 

1278 preservative uses are assessed for those workers involved in the actual treatment 

1279 of the wood with the preservative. This includes operations at a pressure 

1280 treatment facility where workers add the preservative to treatment cylinders, 

1281 remove treated wood charges from the cylinders, check the treated wood to verify 

1282 retention rates, and move the freshly treated wood around the facility (from 

1283 cylinder to drip pad to storage to shipping). Industrial sapstain wood 

1284 preservatives are also assessed at the treatment facility for the application of the 

1285 pesticide. Worker tasks for the non-pressure treatment (non-PT) are slightly 

1286 different than those at pressure treatment (PT) facilities. Separate exposure 

1287 measurements unique to each type of treatment (PT vs non-PT) are used in the 

1288 assessments. 

1289 Exposures to commercial and do-it-yourself uses of treated wood are 

1290 assessed for those installing the treated wood and for those exposed to the 

1291 treated structures (e.g., play sets and decks). 

1292 VII. Discussion of Key Comments on General and Administrative Issues 
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1293 A. Scientific Advisory Panel (SAP) Waivers 

1294 1. Comment. A commenter noted that in the preamble to proposed part 

1295 158, subpart W, EPA cites multiple SAP reports that did not specifically mention 

1296 antimicrobial pesticides. Therefore, the commenter believes these SAP reviews 

1297 were insufficient. Another commenter noted that it has been 9 years since the last 

1298 SAP review and that EPA should request another SAP review prior to 

1299 implementation of proposed part 158, subpart W. Still another commenter 

1300 believes that EPA’s request that the SAP waive its review of proposed part 158, 

1301 subpart W based on the SAP’s 1997 review was improper, and that the SAP 

1302 cannot waive its statutory review obligation.

1303 2. EPA’s Response. EPA disagrees with the comments. On June 3, 1997, 

1304 EPA presented an early version of the part 158, subpart W proposal in an open 

1305 meeting to the SAP. At that time, the SAP provided extensive comments in five 

1306 areas: Toxicology, residue chemistry, ecological effects and environmental fate, 

1307 human exposure, and efficacy. Since then, the SAP has considered many specific 

1308 studies and scientific issues included in proposed part 158, subpart W as part of 

1309 their reviews of guidelines and of data requirements for conventional agricultural 

1310 pesticides (see references 30, 31, 32, 33, and 34 to the proposed rule). In 1997, 

1311 the SAP also noted its concern about the possible effects of antimicrobials on 

1312 WWTPs. Partially in response to the SAP comments, EPA proposed a tiered set 

1313 of environmental fate data requirements that will allow the Agency to better 

1314 characterize potential incidences of antimicrobials in surface waters, as a result of 

1315 down-the-drain uses of antimicrobials. 
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1316 When the Agency prepared to propose 40 CFR part 158, subpart W, EPA 

1317 requested that the SAP waive its review of the about-to-be-proposed part 158, 

1318 subpart W because there were no new scientific issues. The SAP waived its 

1319 review of the about-to-be proposed part 158, subpart W on February 19, 2008. 

1320 The Agency continues to believe that there are no new scientific issues that 

1321 warrant additional review by the SAP. EPA’s request for an SAP waiver for the 

1322 final antimicrobial data requirements rule is discussed in Unit XXIV. FIFRA 

1323 section 25 requires EPA to give the SAP at least 60 days to review proposed 

1324 regulations and 30 days to review final regulations. However, the SAP can 

1325 determine to waive its review during statutory time periods. 

1326 C. Risk Assessments for Wood Preservatives. 

1327 1. Comment. A commenter noted that Canada’s PMRA and USEPA 

1328 conduct risk assessment for wood preservatives differently. EPA’s risk 

1329 assessment is based on the treated wood when used at the final use site, while 

1330 the PMRA’s risk assessment is based at the site where the wood is treated. The 

1331 PMRA also does not distinguish between terrestrial-only or aquatic-only use for 

1332 anti-sapstains and heavy-duty wood preservatives. 

1333 2. EPA’s Response. The Agency acknowledges differences between 

1334 its risk assessment of wood preservatives and that of Canada’s PMRA. As 

1335 previously discussed in Unit VI.A, EPA has re-evaluated its approach for 

1336 determining the data required for a wood preservative product. As part of the re1337 evaluation, EPA considered the human and ecological risks based on exposure 

1338 pathways identified in OECD’s ESD for Wood Preservatives. This ESD identifies 
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1339 potential human and ecological exposures from both treatment of wood at 

1340 processing facilities and in-service uses on land and in water. The Agency 

1341 determined that all treated wood should be considered as having the potential to 

1342 come into contact with surface water. This determination reflects EPA’s concern 

1343 about the potential for the indirect release to surface waters of wood 

1344 preservatives. As a result, EPA is changing its approach to requiring 

1345 environmental and ecological effects studies for wood preservatives. All wood 

1346 preservative risk assessments will now be performed considering that the treated 

1347 wood could end-up either on the land or in the aquatic environment, thus 

1348 increasing harmonization between PMRA and EPA with regard to wood 

1349 preservatives. 

1350 D. Clarity on How and When CR Data is Required 

1351 1. Comment. A commenter asked EPA to specify criteria to determine 

1352 whether a data requirement is “R” (Required) or “CR” (Conditionally Required). 

1353 According to the commenter, the discussion of “R” and “CR” suggests that a data 

1354 requirement labeled “CR” may not be required to be addressed by the applicant. 

1355 A second commenter stated that it is unclear how and when conditionally required 

1356 data are triggered. Another commenter asserted that data requirements should 

1357 be waived only under extraordinary circumstances, and that the use of waivers 

1358 can effectively preclude appropriate regulation of the pesticide under FIFRA. 

1359 2. EPA’s Response. In its proposed data requirement tables, EPA 

1360 specified whether a data requirement is “Required”, “Conditionally Required”, or 

1361 “Not Required” based on how likely the study is needed to complete an 
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1362 assessment of an antimicrobial pesticide. As a rule of thumb, a “required” study is 

1363 likely to be needed 50 percent of the time or more and a “conditionally required” 

1364 study is likely to be needed less than 50 percent of the time. Typically, a 

1365 “conditionally required” study is triggered based on the results of a study that has 

1366 already been conducted. Triggers in the test notes indicate the circumstances 

1367 under which the Agency has learned through experience that the information is 

1368 needed. In many instances, the applicant would be able to make the 

1369 determination that the trigger has been met and should include the data in their 

1370 original submission. In other cases, EPA will make the determination based on its 

1371 review of submitted data and would then request additional data from the 

1372 applicant. EPA encourages applicants to consult with the Agency to determine 

1373 the actual need for the data. 

1374 All data requirements must be addressed by the applicant by either 

1375 conducting the study or submitting information that could fulfill the data 

1376 requirement, such as citing open literature or other data sources, or by requesting 

1377 and receiving a data waiver. EPA grants data waiver requests only on a case-by1378 case basis and only when the available evidence indicates a particular study is 

1379 not needed or that there are particular reasons for not conducting the study. For 

1380 example, if the physical/chemical properties of the chemical did not lend 

1381 themselves to the testing procedure, such as performing an inhalation study with 

1382 a chemical that is a solid and has an extremely low vapor pressure, then a waiver 

1383 might be granted. EPA also grants waivers in exceptional circumstances, for 
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1384 instance, if a test substance is so corrosive that animal studies would cause 

1385 undue pain and suffering. 

1386 VIII. Discussion of Key Comments on Product Chemistry 

1387 The following represent the significant comments received on the need for 

1388 and evaluation of product chemistry studies as proposed by EPA. 

1389 A. Application of Subpart D Product Chemistry Data Requirements to 

1390 Antimicrobials.

1391 1. Comment. A commenter requested that EPA provide adequate 

1392 justification for applying the existing product chemistry data requirements for 

1393 conventional pesticides to antimicrobials without consideration of the highly 

1394 dissimilar chemistries and inapplicability of many of the requirements. 

1395 2. EPA’s Response. It has been EPA’s longstanding practice to require 

1396 product chemistry data. Product chemistry data are required to identify the 

1397 chemicals used to manufacture a product and to understand the physical and 

1398 chemical properties of the ingredient or product. Such information is generally 

1399 independent of the intended use pattern. Product chemistry data are used during 

1400 label development to identify information to be included on the label, such as the 

1401 flammability statement, and directions for disposal of the product. Hence, despite 

1402 any differences between conventional and antimicrobial pesticides, the Agency 

1403 believes it is appropriate to apply the same product chemistry data requirements 

1404 to antimicrobials as required for conventional pesticides. The guidelines for 

1405 conducting product chemistry studies offer flexibility to account for differences 

1406 between chemical classes. 
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1407 B. Lack of Adequate Opportunity for Review of Product Chemistry Data 

1408 Requirements 

1409 1. Comment. One commenter asserted that registrants of antimicrobial 

1410 pesticides were not given the opportunity to review and comment on conventional 

1411 pesticide data requirements that are now being proposed for antimicrobial 

1412 pesticides. 

1413 2. EPA’s Response. .In the preamble to proposed part 158, subpart W, 

1414 EPA proposed to apply the product chemistry data requirements for conventionals 

1415 in 40 CFR part 158 subpart D to antimicrobial pesticides. Therefore, during the 

1416 public comment period for the proposed part 158, subpart W, from October 8, 

1417 2008, to April 6, 2009, any interested party could have commented on the product 

1418 chemistry data requirements in subpart D (which have been in place since 

1419 October 2007) and their potential applicability to antimicrobials. 

1420 IX. Discussion of Key Comments on Product Performance Data 

1421 Requirements 

1422 The following represent the significant comments received on the need for 

1423 and evaluation of product performance studies as proposed by EPA. Changes 

1424 from the proposed rule to the final rule are also described.

1425 A. Product Performance Guidelines 

1426 1. Comment. Several commenters shared their belief that EPA was 

1427 seeking to avoid comment on the product performance data requirements in the 

1428 proposed rule by stating that the Agency” is not proposing to revise product 

1429 performance data requirements” at this time. Another commenter asked how the 
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1430 product performance section of the proposed rule could be finalized without the 

1431 810 guidelines? 

1432 2. EPA’s Response. The proposed product performance data 

1433 requirements table contained the older 91 series guidelines. As stated in the 

1434 proposed rule the requirements being proposed were “nearly identical” to the 

1435 existing data requirements in § 158.400 and 161.640, and the table was 

1436 “transferred essentially unchanged” (73 FR 59391). Since the 2008 proposed 

1437 rule, EPA published the draft 810 guidelines for comment. Four of the 810 series 

1438 guidelines (810.2000, 810.2100, 810.2200, and 810.2300 for sterilants, 

1439 disinfectants and sanitizers) were published in the Federal Register for public 

1440 comment on January 27, 2010 (75 FR 4308). These guidelines represent the 

1441 Agency’s current recommendations for conducting product performance studies to 

1442 support antimicrobial pesticide label claims. That Notice of Availability announced 

1443 that the 810 guidelines series would be incorporated into the final data 

1444 requirements regulation: As announced, in this final rule EPA is replacing the 91 

1445 series designations proposed in the part 158, subpart W product performance 

1446 table with the appropriate 810 Series Guideline numbers and names. Thus, 

1447 commenters had an opportunity to comment on the inclusion of the 810 series in 

1448 the final Product Performance Data Requirements table. Three additional product 

1449 performance guidelines (810.2400, 810.2500, and 810.2600) should be published 

1450 for comment in a timeframe similar to that of publication of the final rule for 

1451 Antimicrobial Data Requirements. See Unit XVIII for a discussion on guidelines. 

1452 B. Emerging Pathogens
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1453 1. Comment. A commenter asked why there is no formal regulatory 

1454 practice for registering products to address public health emergencies or 

1455 emerging pathogens promptly and effectively? 

1456 2. EPA’s Response. EPA does not believe that the promulgation of a rule 

1457 dealing with data requirements is the appropriate place to address emerging 

1458 pathogens. A major consideration in the Agency's process for addressing public 

1459 health emergencies and emerging pathogens is to work closely with the Centers 

1460 for Disease Control and Prevention (CDC), Department of Agriculture (USDA), 

1461 and FDA, as appropriate, to provide a timely and accurate response to these 

1462 situations. Under FIFRA section 18, the Agency also has authority to grant certain 

1463 exemptions from the provisions of FIFRA and also to approve the use of 

1464 unregistered pesticides when emergency conditions exist. Additionally, in April 

1465 2008, the Agency implemented a disinfection hierarchy policy for addressing 

1466 emerging viral pathogens. Information on this policy is available on the EPA 

1467 website at http://www.epa.gov/oppad001/disinfection_hier.htm. EPA believes that 

1468 emerging pathogens require flexibility and speed in disseminating information and 

1469 seeks to address such situations in a prompt and effective manner. 

1470 C. Definitions of Sanitizer and Disinfectant 

1471 1. Comment. Several commenters claimed that the proposed definitions 

1472 do not reflect the work done by the regulated community in cooperation with EPA 

1473 since 1999. In particular, these commenters did not agree with the proposed 

1474 definitions of sanitizer and disinfectant. 

1475 2. EPA’s Response. Since the publication of the proposed rule, the 
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1476 definitions, including those for sanitizer and disinfectant, were published in the 

1477 Federal Register for public comment on January 27, 2010, as part of requesting 

1478 comment on draft guideline 810.2000. After further review of the comments 

1479 submitted on the proposed definition for disinfectant and sanitizer, the Agency has 

1480 revised the definitions that had been proposed for both part 158, subpart W and 

1481 the 810 Guidelines. EPA believes that the definitions being codified today reflect 

1482 the input received from the regulated community in multiple submissions. The 

1483 definitions for sanitizer and disinfectant will be the same in both part 158, subpart 

1484 W and in the 810 Guidelines. 

1485 The definition for disinfectant is being revised from, “Disinfectant means a 

1486 substance, or mixture of substances that destroys or eliminates a specific species 

1487 of infectious or public health microorganism, but not necessarily bacterial spores, 

1488 in the inanimate environment” to read, “Disinfectant means a substance, or 

1489 mixture of substances, that destroys or irreversibly inactivates bacteria, fungi and 

1490 viruses, but not necessarily bacterial spores, in the inanimate environment.” 

1491 The definition for sanitizer is being revised from, “Sanitizer means a substance, or 

1492 mixture of substances that reduces the bacterial population in the inanimate environment by 

1493 significant numbers, but does not destroy or eliminate all bacteria or other microorganisms” to 

1494 read, “Sanitizer means a substance, or mixture of substances that reduces the bacterial population 

1495 in the inanimate environment by significant numbers, (e.g., 3 log10 reduction) or more, but does 

1496 not destroy or eliminate all bacteria. Sanitizers meeting Public Health Ordinances are generally 

1497 used on food contact surfaces and are termed sanitizing rinses.” 

1498 The definitions for fungicide, sterilant, tuberculocide and virucide are being 

1499 revised to include the following phrase: “or mixture of substances.” Inclusion of 
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1500 this phrase in all of the definitions in § 158.2203 for types of products that bear 

1501 public health claims (excepting microbiological water purifier) means consistency 

1502 in the definitions and an acknowledgement that the destroying, reducing, or 

1503 inactivating may be accomplished via more than a single substance. Also, this 

1504 makes these definitions similar to the FIFRA section 2(u) definition of pesticide 

1505 which also contains the phrase “or mixture of substances.” 

1506 Additionally, the definition for virucide is being revised to include the word 

1507 irreversibly, as follows: “Virucide means a substance, or mixture of substances, 

1508 that destroys or irreversibly inactivates viruses in the inanimate environment,” thus 

1509 reading similar to the definition for tuberculocide. Additionally, the definition for 

1510 sterilant will be revised to remove the second sentence of the proposed definition: 

1511 “For purposes of this subpart, ‘sporicide’ and ’sterilant’ are synonymous.” EPA no 

1512 longer requires that products that make sporicidal claims also make sterilant 

1513 claims. 

1514 D. Nonpublic Health Data and Claims 

1515 1. Comment. A commenter asked that the issue of when to generate 

1516 efficacy data for nonpublic health products be discussed, since registrants are 

1517 required to develop data to substantiate label claims. 

1518 2. EPA’s Response. The Agency believes this issue has been addressed 

1519 in § 158.2220 "Product Performance," which clearly states, "Each applicant must 

1520 ensure through testing that his product is efficacious when used in accordance 

1521 with label directions and commonly accepted pest control practices.” However, to 
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1522 clarify the issue further, the Agency is adding a definition for nonpublic health 

1523 claims that will appear as 40 CFR 158.2204(b): 

1524 Nonpublic health claim. An antimicrobial pesticide is 

1525 considered to make a nonpublic health claim if the 

1526 pesticide product bears a claim to control 

1527 microorganisms of economic or aesthetic significance, 

1528 where the presence of the microorganism would not 

1529 normally lead to infection or disease in humans. 

1530 Examples of nonpublic health claims include, but are 

1531 not limited to, algaecides, slimicides, preservatives 

1532 and products for which a pesticidal claim with respect 

1533 to odor sources is made. 

1534 

1535 Additionally, EPA is revising 40 CFR 158.2220(c)(3) to read: 

1536 (3) Product performance data for each product that 

1537 bears a nonpublic health claim. Each product that 

1538 bears a nonpublic health claim, as described in 

1539 §158.2204(b), must be supported by product 

1540 performance data. Each registrant must ensure 

1541 through testing that his product is efficacious when 

1542 used in accordance with label directions and 

1543 commonly accepted practices. The Agency reserves 

1544 the right to require, on a case-by-case basis, 

1545 submission of product performance data for any 

1546 pesticide product registered or proposed for 

1547 registration or amendment. 

1548 

1549 Also, EPA has posted on the Antimicrobials Division website the parts of the 91 

1550 Guideline series that apply to testing of nonpublic health products. Although 

1551 these guidelines are from 1982, they are still relied on to develop data to support 

1552 nonpublic health label claims. EPA acknowledges that some of the references in 

1553 the 1982 guidelines are to the older 91 series, which is being replaced by the 810 

1554 series. To assist readers, EPA has also posted a cross-walk table so readers can 

1555 locate the applicable section of the 810 Guidelines. 

1556 X. Discussion of Key Comments on Toxicology Data Requirements 
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1557 The following represent the significant comments received on the need for 

1558 and evaluation of toxicology studies as proposed by EPA. Changes from the 

1559 proposed rule to the final rule are also described.

1560 A. TTC Approach

1561 1. Comment. There should be a threshold of toxicological concern (TTC) 

1562 type of approach for antimicrobials. 

1563 2. EPA’s Response. OPP’s Antimicrobials Division is aware of the TTC 

1564 concept, and in conjunction with ILSI, is currently pursuing the development of an 

1565 application of the TTC concept to evaluate antimicrobial pesticides. At this time, 

1566 EPA anticipates a timeframe of 2 to 3 years for development. Once a TTC-based 

1567 approach has been developed and piloted, then EPA would consider when/if the 

1568 approach should be included in part 158, subpart W. 

1569 B. Test Note to Neurotoxicity Studies 

1570 1. Comment. A commenter stated that proposed test note 6 to the 

1571 proposed toxicology table in § 158.2230 triggering the neurotoxicity studies is 

1572 contradictory and unclear. The commenter asked how the absence of a 

1573 neurotoxicity screen in the 90-day oral rodent study would impact proposed test 

1574 note 6? 

1575 2. EPA’s Response. Proposed test note 6 specifies that if the 

1576 neurotoxicity screen that occurs in the 90-day oral rodent study or any other data 

1577 demonstrate neurotoxic effects, then both the acute neurotoxicity study and the 

1578 90-day neurotoxicity study are triggered. For certain use patterns with the 

1579 potential for larger exposures (most notably food exposures), all three of these 
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1580 studies are initially required. According to proposed test note 8 to the proposed 

1581 toxicology table in § 158.2230, the applicant may combine the 90-day oral toxicity 

1582 study and the 90-day neurotoxicity study by adding a separate group of test 

1583 animals. 

1584 However, for some use patterns, the 90-day oral study is required, and the 

1585 other two studies are conditionally required, being triggered by proposed test note 

1586 6. EPA acknowledges that when only the 90-day oral study is required, an 

1587 applicant is at a disadvantage in terms of any chance for combining the 90-day 

1588 neurotoxicity study with the oral study: Once the 90-day oral study with its 

1589 neurotoxicity screen has been performed, and neurotoxic effects are identified, 

1590 then it is not possible to add a separate group of test animals to the already 

1591 conducted study. 

1592 As a point of clarification, EPA is adding a new test note to the final 

1593 Toxicology Table in § 158.2230(g) to clarify that the neurotoxicity screen that is 

1594 part of the 90-day oral study is not equivalent to a 90-day neurotoxicity study. If 

1595 the 90-day oral toxicity study does not have a neurotoxicity screen, then the acute 

1596 neurotoxicity study in the rat would be required. The new test note also includes: 

1597 “if the 90-day oral rodent study does not include a neurotoxicity screen, then the 

1598 acute neurotoxicity study will be required.” As part of renumbering, this new test 

1599 note is now test note 11 to the Toxicology Table in the final rule, § 158.2230(g). 

1600 C. End-Product Use-Dilution Toxicity Testing

1601 1. Comment. Several commenters stated their belief that acute end 

1602 product use-dilution toxicity testing should be optional and requested greater 
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1603 clarification on when to test a diluted product. The commenters asked whether 

1604 extrapolation from the active ingredient or as-sold acute toxicity testing is 

1605 acceptable? Another commenter claimed that requiring end-product six-pack 

1606 testing of one or more dilutions is duplicative. 

1607 2. EPA’s Response. Proposed test note 2 to the proposed toxicology table 

1608 in § 158.2230, specifies how to conduct acute toxicity testing for end-use products 

1609 (EP). EP testing is conducted on the product as formulated for sale and 

1610 distribution. From the EP acute toxicity studies, EPA derives toxicity categories 

1611 which are then used to determine the precautionary labeling statements on the 

1612 product. However, it is common for some products to be diluted before being 

1613 used. The use-dilution testing is in addition to the as-formulated-for-sale testing 

1614 since there are exposures to both. Acute toxicity testing on the product that has 

1615 been diluted-for-use supplies the information needed to derive precautionary 

1616 statements for the user of the product. EPA is revising proposed test note 2 to 

1617 make this clearer. 

1618 D. The Phrasing “limited portion of the human lifespan” 

1619 1. Comment. Several commenters asked EPA to identify the criteria to 

1620 determine “repeated human exposure over a limited portion of the human life 

1621 span.” They asked EPA to specifically describe what the phrase “human 

1622 exposure is not purposeful” means? 

1623 2. EPA’s Response. Proposed test note 11 to the proposed toxicology 

1624 table in § 158.2230, specifies the triggers that would require the performance of a 

1625 90-day oral study in the non-rodent. EPA has re-evaluated this test note and 
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1626 decided to remove test note 11 from proposed part 158, subpart W. Proposed 

1627 test note 11(i) contained the phrase “repeated human exposure over a limited 

1628 portion of the human life span.” EPA agrees that this phrase is not useful. 

1629 Proposed test note 11(ii) contained a trigger for any indirect food use that would 

1630 have been considered to be a “low exposure.” Given the restructuring of the final 

1631 Toxicity Data Requirements Table, i.e., the shift away from using high and low 

1632 exposure as the table headers to a food/nonfood approach, test notes 11(i) and 

1633 11(ii) are no longer needed. In the final Toxicity Table in § 158.2230(g), the data 

1634 required for an indirect food-use is specified directly (in the table header) and a 

1635 trigger is not needed. As discussed in Unit X.B, proposed test note 11 is replaced 

1636 by a different test note as part of re-numbering. 

1637 Proposed test note 12 to the proposed toxicology table in § 158.2230, 

1638 specifies three triggers that would require the performance of a 21/28-day dermal 

1639 study. EPA has also re-evaluated test note 12 and agrees that the phrases 

1640 “repeated human exposure over a limited portion of the human life span” and 

1641 “human exposure is not purposeful” are not useful. EPA has decided to remove 

1642 the first two of the triggers. Therefore, the 21/28 day dermal study is now 

1643 triggered if the intended use of the antimicrobial pesticide product is expected to 

1644 result in dermal human exposure to the product, data from a subchronic 90-day 

1645 dermal toxicity study are not available, and the 90-day dermal toxicity study has 

1646 not been triggered (the third proposed trigger). 

1647 E. Mouse Carcinogenicity Study
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1648 1. Comment. According to several commenters, the mouse 

1649 carcinogenicity study does not provide useful information, and is, in fact, not 

1650 suited for determining/extrapolating human carcinogenicity. They contended that 

1651 EPA should no longer require the mouse carcinogenicity study. This would also 

1652 mean that there is no need for the mouse range-finding study. 

1653 2. EPA’s Response. The issue regarding the usefulness of the mouse for 

1654 carcinogenicity testing is one that is currently under debate by the OPP. 

1655 Currently, carcinogenicity testing, whether for conventional under § 158.500 or for 

1656 antimicrobials under part 158, subpart W requires testing in two rodent species. 

1657 However, OPP is currently conducting a comprehensive analysis of its rodent 

1658 chronic bioassay database to document the utility of the mouse bioassay for both 

1659 cancer risk assessment and Reference Dose (RfD) derivation for non-cancer 

1660 endpoints. When this analysis is completed, a recommendation will be made 

1661 regarding the testing needed for cancer hazard identification. OPP anticipates 

1662 completing this analysis during 2012. Once OPP’s internal review process is 

1663 complete, then it is likely that EPA would solicit review and comment by the 

1664 FIFRA SAP. If at a later date, the determination is made to alter the 

1665 carcinogenicity data requirements, then appropriate changes would be proposed 

1666 to be made to data requirements and regulations pertaining to conventionals, 

1667 biochemicals and microbials, and antimicrobials through rulemaking. 

1668 F. Ames Assay

1669 1. Comment. A commenter argued that the Ames assay should not be 

1670 required, because it is inappropriate for antimicrobials that kill bacteria. 
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1671 2. EPA’s Response. It is recognized that the Ames assay may not be 

1672 useful for assessment of mutagenic potential of antimicrobial pesticides, as this 

1673 test uses strains of bacteria as the primary test material, and antimicrobials are 

1674 designed to kill, among other things, bacteria. So, the bacteria may be killed 

1675 before mutagenic effects are demonstrated. However, for some antimicrobial 

1676 pesticides, the Ames assay has already been conducted and if the Ames assay 

1677 was conducted at levels that do not cause toxicity to the bacterial strains tested, 

1678 then the study may be acceptable to fulfill the reverse mutation asay requirement. 

1679 However, if an Ames assay has not yet been conducted for a particular 

1680 antimicrobial, then, the Ames assay should not be conducted. In this final rule, 

1681 test note 32 for the reverse mutation assay requirement to the final Toxicology 

1682 Table in § 158.2230(g), is revised to allow reliance on previously-conducted Ames 

1683 tests when the bacteria strain was not killed, but to state a preference for assays 

1684 such as an in vitro mammalian cell assay, (e.g., the mouse lymphoma TK +/- 

1685 assay). 

1686 G. Dermal Absorption Studies

1687 1. Comment. A commenter argued that EPA should accept in vitro skin 

1688 penetration data. According to the commenter, accepting such data would 

1689 harmonize with requirements in the European Union (EU) and elsewhere. The 

1690 commenter pointed to well-established OECD guidelines for these studies. The 

1691 commenter also asserted that proposed test note 37 to the proposed toxicology 

1692 table in § 158.2230, addressing the requirement for a dermal absorption study, 

1693 should not apply to corrosive/irritant products. 
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1694 2. EPA’s Response. The Agency has, on a case-by-case basis, used in 

1695 vitro dermal absorption studies to determine the magnitude of dermal absorption 

1696 of pesticide chemicals. However, the Agency has not adopted an official policy of 

1697 using only in vitro data to support these decisions. The OECD guideline 428, while 

1698 describing an in vitro method for dermal absorption, does not rule out the use of in 

1699 vivo data along with in vitro data to determine dermal absorption. Further, the test 

1700 guideline notes that formal validation studies of the in vitro method have not been 

1701 performed. 

1702 The Agency is working on developing a more formal policy that would use 

1703 both in vivo and in vitro dermal penetration data in a weight-of-evidence (WOE) 

1704 determination in appropriate cases. The Agency would always consider QSAR or 

1705 other models, submitted in support of the determination of dermal absorption. 

1706 The decision to accept such information is the Agency’s, based on its review and 

1707 evaluation of the submission. 

1708 Proposed test note 37 to the proposed toxicology table in § 158.2230, 

1709 specifies that the trigger for requiring a dermal penetration study are the results 

1710 from a risk assessment “assuming that dermal absorption is equal to oral 

1711 absorption.” This means that EPA assumes 100 percent dermal absorption. If a 

1712 subchronic dermal study and/or dermal absorption data are not available, then a 

1713 risk assessment could be conducted using the default assumption of equivalent 

1714 absorption by the dermal and oral routes of exposure. If unacceptable risks are 

1715 found, then either the subchronic dermal study or a dermal absorption study 

1716 would be required. EPA recognizes that the assumption of 100 percent dermal 
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1717 absorption is conservative; however, this assumption would only be used in the 

1718 absence of an acceptable dermal subchronic study or dermal absorption data. In 

1719 this final rule, test note 37 to the Toxicology Table in § 158.2230(g), is revised to 

1720 clarify this process. EPA also agrees that corrosive/irritant products should not be 

1721 tested in dermal absorption studies. Therefore, test note 3 to the Toxicology Table 

1722 in § 158.2230(g), which specifies that testing is not needed for corrosive 

1723 materials, is added as a trigger for not requiring the dermal absorption study. 

1724 H. Tiering

1725 1. Comment. One commenter argued that EPA has not provided 

1726 meaningful tiering for its toxicology requirements for antimicrobials. Another 

1727 commenter claimed that exposure alone is not an appropriate criterion to use for a 

1728 tiered testing scheme, that both exposure and risk should be considered. A third 

1729 commenter asserted that the high and low human exposure categories for toxicity 

1730 are not appropriate and suggested that a tiered scheme such as that used for 

1731 environmental fate data requirements would be more appropriate. 

1732 2. EPA’s Response. EPA disagrees with these comments. In its 

1733 proposed rule EPA proposed a tiered testing scheme for toxicology testing that 

1734 was based on the amount of exposure as defined by use patterns. Based on its 

1735 experience in conducting risk assessments, EPA understands which use patterns 

1736 have exposures of higher duration and magnitude, and therefore could have 

1737 greater risks. Use patterns with higher exposures require more submission of 

1738 data than use patterns with lower exposures. 

1739 I. Guideline Numbers in CFR 
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1740 1. Comment. A commenter stated that the final rule should not specify a 

1741 guideline number. Instead, the data requirement tables should describe the 

1742 endpoint in question, and the information needed for EPA’s risk assessment. 

1743 OPP could develop guidance that could be placed on the web. 

1744 2. EPA’s Response. EPA agrees with this comment. The guideline 

1745 number column could be removed from the table. Instead, EPA could have an 

1746 internet page that describes multiple methods of fulfilling the data requirements. 

1747 An internet table could be updated faster to reflect newer techniques than 

1748 rulemaking to revise regulation in the CFR. However, there is also value in having 

1749 the guideline number in the CFR, which then shows the available guidelines 

1750 relevant to the particular study that should be considered in addressing the 

1751 requirement. EPA has made no decision on whether or not to initiate a 

1752 rulemaking to remove all the guideline numbers from the data requirement tables 

1753 in 40 CFR part 158. The tables finalized in subpart W in this rule include guideline 

1754 numbers. 

1755 J. Animal Testing 

1756 1. Comment. A commenter requested that EPA specifically state in its 

1757 regulations that non-animal methods are acceptable for fulfilling a data 

1758 requirement. The commenter argued that the Draize study (the acute eye 

1759 irritation study) in rabbits should be eliminated. 

1760 2. EPA’s Response. Non–animal test methods are continually being 

1761 examined for use in fulfilling the toxicology data requirements that are used to 

1762 assess the hazard of pesticide chemicals. However, in order for non-animal 
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1763 approaches to be used for fulfilling toxicology data requirements, these 

1764 approaches must first be scientifically validated to ensure that they are as good as 

1765 the existing test method for predicting hazard and also assessed to determine 

1766 whether they meet the Agency’s “3 R” goals of reduce, refine, and replace the 

1767 use of animals in testing. With respect to antimicrobial pesticides, the Agency has 

1768 started to explore such approaches. One example of this is the voluntary pilot 

1769 program for eye irritation testing of antimicrobial pesticides using non–animal test 

1770 methods, found at http://www.epa.gov/oppad001/eye-irritation.pdf.

1771 K. Derivation of 200 Parts per Billion Criterion 

1772 1. Comment. A commenter asked whether the 200 parts per billion (ppb) 

1773 level used as the dividing line between high and low human exposures is the 

1774 concentration of a substance in an adult’s daily food consumption? 

1775 2. EPA’s Response. The derivation of the 200 ppb level was previously 

1776 established by FDA for indirect food use biocides, and is described in the 

1777 proposed rule (73 FR 59394, October 8, 2008). (Also, see document 10 in the 

1778 docket at http://www.regulation.gov.) As discussed in the proposed rule, the 200 

1779 ppb is derived by dividing FDA’s cumulative exposure upper limit of 1000 ppb 

1780 level by 5 to account for the fact that antimicrobial pesticides (e.g., biocides) are a 

1781 class of pesticide that are generally toxic by design. The 200 ppb level is the 

1782 concentration of the antimicrobial residues in or on the food item. EPA is using 

1783 200 ppb as a delineation consistent with the FDA’s toxicology recommendations 

1784 for food contact substances. Therefore, those indirect food uses that have 

1785 residues that are less than or equal to 200 ppb in or on the food item usually have 
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1786 fewer data requirements than those that have residues that are greater than 200 

1787 ppb in or on the food item. For clarity, the following information concerning the 

1788 200 ppb level and its derivation from FDA levels has been added to § 

1789 158.2230(d): 

1790 The 200 ppb level was originally used by the Food 

1791 and Drug Administration with respect to the 

1792 concentration of residues in or on food for tiering of 

1793 data requirements for indirect food use biocides. The 

1794 Agency has also adopted this same residue level for 

1795 determining toxicology data requirements for indirect 

1796 food uses of antimicrobial pesticides. The 200 ppb 

1797 level is the concentration of antimicrobial residues in 

1798 or on the food item. 

1799 

1800 L. Use of OECD Guidelines for EPA Registrations 

1801 1. Comment. A commenter asked EPA to consider incorporating the 

1802 following OECD guidelines into the new part 158, subpart W to reduce the number 

1803 of animals killed in LD50 tests: OECD guidelines 436; Acute Inhalation Toxicity - 

1804 Acute Toxic Class Method, and revised 223; Avian Acute Oral Toxicity Test, and 

1805 Short Guidance on the Threshold Approach for Acute Fish Toxicity. 

1806 2. EPA’s Response. OPP does not have a policy for use of OECD 436 for 

1807 acute inhalation toxicity. If a study conducted according to OECD 436 were 

1808 submitted for the purpose of assessing acute inhalation toxicity, EPA would 

1809 review and accept the results if the study were conducted in an acceptable 

1810 manner and provided sufficient information to fulfill the data requirement. 

1811 Similarly, if a study conducted according to OECD 223 or the Threshold 

1812 Approach, were submitted, then EPA would review the study and then make a 
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1813 determination on whether the study was conducted in an acceptable manner and 

1814 provided sufficient information to fulfill the data requirement. 

1815 M. Alternative Formats for Toxicology Data Requirements Table Suggested by 

1816 Commenters 

1817 1. Comment. In the comments submitted to EPA, the commenters 

1818 suggested two alternative toxicity data requirement approaches for EPA to 

1819 consider. Alternative approach 1 was organized in paragraphs and alternative 

1820 approach 2 was in a table format similar to that proposed by EPA. 

1821 2. EPA’s Response. The commenters provided two alternative 

1822 approaches for toxicology data requirements for antimicrobials. As stated by the 

1823 commenter, alternative approach 1 was “intended to provide clearer instructions 

1824 to registrants,” attempted “to fully incorporate the new science” of integrative 

1825 approaches to testing, and included “a threshold concept for toxicological 

1826 concerns.” (ACC Comment in the docket at http://www.regulations.gov; document 

1827 EPA-HQ-OPP-2008-0110-0088.6; Appendix E, entitled “Comments on Proposed 

1828 Data Requirements for Toxicology” p. 24). The commenter did not provide to 

1829 EPA the same or similar table-type of format used for part 158 data requirements. 

1830 There were no test notes to define the triggers for moving from tier to tier. The 

1831 commenter acknowledged that their suggested alternative approach 1 would 

1832 require “expert scientific judgment” (p. 25), and discussed that in the proposed 

1833 rule (59423) that EPA had indicated the need for scientific position papers, and 

1834 recommendations for internal and external review. EPA considers alternative 

1835 approach 1 to be a dramatic departure from EPA’s proposal, and agrees with the 
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1836 commenter that certain scientific issues may not be ready for codification. EPA 

1837 does not believe, at this time, that this approach meets the needs of the Agency, 

1838 or has any advantages over the table format. EPA found the paragraph 

1839 explanations unclear. As acknowledged by the commenter, the paragraph format 

1840 would result in a more complex decision tree that would require a significantly 

1841 greater amount of interpretation and consultation when compared to the existing 

1842 table formats. There would be a significant learning curve for both EPA and 

1843 those members of the public that have become accustomed to data requirement 

1844 tables such as in part 158. Within this response, EPA has responded to 

1845 alternative approach 1 in totality. EPA notes that the individual scientific issues 

1846 raised within the paragraphs are addressed separately, as they were separated 

1847 into the various disciplinary areas of the toxicology comments. 

1848 EPA has also evaluated alternative approach 2. This alternative approach 

1849 is in a table-type of format with a strict split between food and nonfood uses. The 

1850 test notes developed by the commenters are extremely detailed and contain 

1851 information that EPA believes is more appropriate in guidance. However EPA has 

1852 used the suggested test notes to revise its proposed testnotes as appropriate. 

1853 For example, the commenters’ suggested test note 32 to the in vivo cytogenetics 

1854 study is clearer than EPA’s proposed test note 34. Therefore EPA is revising test 

1855 note 34 to the final Toxicology Table in § 158.2230(g), accordingly 

1856 As discussed previously, as a result of comments received, EPA is no 

1857 longer using the terms “high human exposure” and “low human exposure” as 

1858 proposed for the antimicrobial toxicology data requirements table. Instead, in the 
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1859 final rule, EPA is now using a food/nonfood approach with some similarities to that 

1860 of the toxicology data requirements table for conventional pesticides to distinguish 

1861 the use patterns with higher exposure that need more toxicity data from those that 

1862 need less. Accordingly, the table headers for the Toxicology Data Requirements 

1863 Table in the final rule are: “Direct Food Uses;” “Indirect Food Uses (>200 ppb);” 

1864 “Indirect Food Uses (≤200 ppb);” “Swimmers, Aquatic Areas, Wood Preservatives, 

1865 Metal Working Fluids;” and “All Other Nonfood Uses.” 

1866 Unlike conventional pesticide chemicals, a strict food/nonfood use “split” for 

1867 delineating data requirements is not appropriate for antimicrobial chemicals. Such 

1868 an approach does not fully address the unique use patterns for antimicrobials, 

1869 most specifically, those involving indirect food uses. As a result of comments 

1870 received, EPA decided to employ a modification of the food/nonfood approach to 

1871 delineate the specific data requirement needs for antimicrobial pesticides. 

1872 The commenter has also asked that EPA include within subpart W a new § 

1873 158.2235 which would be analogous to 40 CFR 158.510 for conventional 

1874 chemicals (Tiered Testing Options for Nonfood Use Pesticides). EPA does not 

1875 believe this is needed for antimicrobials. Once it has been determined that the 

1876 use is nonfood, then certain of the nonfood use scenarios require the submission 

1877 of more data, and certain require the submission of less data. As specified in the 

1878 column headings for Nonfood Uses, swimming pools, aquatic areas, wood 

1879 preservatives, and metal working fluids require a particular set of data. All other 

1880 nonfood uses require less data. Thus, the tiering is already built into the approach 

1881 used for antimicrobials. 
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1882 XI. Discussion of Key Comments on Nontarget Organism Data 

1883 Requirements 

1884 The following represent the significant comments received on the need for 

1885 and evaluation of nontarget organism studies as proposed by EPA. Changes from 

1886 the proposed rule to the final rule are also described. 

1887 A. Need for Ecotoxicity Data for Indoor Uses 

1888 1. Comment. Several commenters argued that there are few antimicrobial 

1889 use patterns where ecological effects information would be relevant to an 

1890 assessment under FIFRA because there is no expectation of environmental 

1891 exposure 

1892 2. EPA’s Response. As explained in the proposed rule, there is now a 

1893 greater concern regarding indoor uses of antimicrobials because those uses can 

1894 lead to environmental exposure when they go down-the-drain. The Agency and 

1895 the scientific community have more recently become concerned with 

1896 pharmaceuticals and personal care products (PPCPs), which are now recognized 

1897 as environmental contaminants. A subset of these PPCPs includes antimicrobial 

1898 pesticide products, some of which are being detected in various environmental 

1899 compartments/media [e.g., surface water and WWTP biosolids]. As discussed in 

1900 the proposed rule (73 FR 59407), these findings are notable, because many of the 

1901 antimicrobial pesticides detected are registered for only indoor use patterns. 

1902 There are many uses for which a high potential for environmental exposure 

1903 exists, especially outdoor uses such as wood preservatives, ballast water 

1904 treatments, antifoulant paints and coatings, aquatic areas, and others. These 
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1905 uses may require a more extensive data set that could include acute and chronic 

1906 tests in both freshwater and saltwater, and possibly in the sediment as well as the 

1907 water column. If the effluent from a WWTP is likely to contain an antimicrobial 

1908 pesticide, or if the antimicrobial is likely to partition to the sludge that is derived 

1909 during the treatment process, then indoor uses could require additional testing to 

1910 further characterize the hazard and the risk. 

1911 B. Transformation Products

1912 1. Comment. Several commenters questioned, how a registrant would 

1913 determine if “transformation products” would need to be tested? With regard to 

1914 the criteria for when testing is required on transformation products, another 

1915 commenter stated their belief that any data developed to assess the potential risk 

1916 to nontarget organisms should be developed with the appropriate residue of 

1917 concern (ROC) (i.e. degradation product, metabolite, or TGAI) rather than always 

1918 testing with the TGAI. Still another commenter asked how would EPA determine 

1919 that the transformation products are “more toxic, persistent, bioaccumulative or 

1920 have been shown to cause adverse effects in mammalian or aquatic reproductive 

1921 studies?” Finally, a commenter requested that EPA should explain what is 

1922 considered “stable” in the environment in proposed test note 3 to the proposed 

1923 nontarget organism table in § 158.2240. 

1924 2. EPA’s Response. The Agency evaluates the need for nontarget 

1925 organism testing of transformation products on a case-by-case basis, using 

1926 several sources of information, which includes, most importantly, environmental 

1927 fate data. EPA proposed to require nontarget organism testing of 
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1928 transformation/degradation products or leachate residues in proposed § 

1929 158.2240(a)(3) and (4). To respond to this comment, EPA also considered a 

1930 similar comment on transformation/degradation products or leachate residues for 

1931 environmental fate testing (see Unit XIV.B). In response to these comments, 

1932 EPA determined to clarify and revise the criteria for testing of 

1933 transformation/degradation products and leachate residues for nontarget plant 

1934 and organisms, and environmental fate, (§ 158.2250(b), 158.2240(a)(3), and 

1935 158.2280(a)(2)) to read as follows: 

1936 Data on transformation/degradation products or 

1937 leachate residues of the parent compound are also 

1938 required to support registration, if the Agency 

1939 determines that the 

1940 transformation/degradation/leachate products meet 

1941 one of the following criteria: 

1942 (i) More toxic, persistent, or bioaccumulative than the 

1943 parent, 

1944 (ii) Have been shown to cause adverse effects in 

1945 mammalian or aquatic reproductive studies, or 

1946 (iii) The moiety of concern (i.e., functional group in the 

1947 parent chemical molecule that imparts adverse 

1948 effects) remains intact. 

1949 

1950 As explained in Unit XIV.B environmental fate studies provide information 

1951 on the stability and persistence of the active ingredient and degradation products 

1952 in the various environmental media. If the environmental fate studies on the 

1953 parent indicate the transformation/degradation product(s) is, for example, more 

1954 persistent in soils, then it is possible that nontarget plants or animals could be 

1955 exposed to the degradate. Once the transformation products and the 

1956 environmental compartment in which they occur are identified, then the available 
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1957 toxicology data (e.g., reproduction tests, developmental tests, non-rodent chronic 

1958 studies) are reviewed to determine toxicity. 

1959 After reviewing all available information, then EPA would use these criteria 

1960 to determine if ecological effects data on the transformation/degradation products 

1961 or leachate residues are required for either nontarget organisms or nontarget 

1962 plants. EPA believes that nontarget plant protection data may sometimes be 

1963 needed when the Agency begins conducting species-specific endangered species 

1964 assessments for antimicrobial pesticides. 

1965 EPA does not use the term “residue of concern (ROC)” in the final 

1966 Nontarget Organisms Data Requirements Table. Instead, the appropriate test 

1967 material(s), such as TGAI, degradate, or TEP, is specified in the data 

1968 requirements table in § 158.2240. This approach is also used for the conventional 

1969 nontarget organism table in part 158. Generally, for ecological testing, the TGAI 

1970 testing is performed first, and then additional testing on a transformation product 

1971 may be required based on the process described above. Depending on how fast 

1972 a substance decays, a nontarget organism or plant could actually be exposed to a 

1973 mixture of the parent and one or more degradation/transformation products. 

1974 C. Test note 7 to the Nontarget Organism Table and Wood Preservatives

1975 1. Comment. Proposed test note 7 to the proposed nontarget organism 

1976 data requirements table in § 158.2240 specifies the triggers for requiring typical 

1977 end-use product (TEP) testing for the acute freshwater invertebrate study and 

1978 acute freshwater fish study. A commenter asked whether, even though, the wood 
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1979 preservatives use pattern is specified as “NR,” could the TEP testing be required 

1980 because of the triggers in test note 7. 

1981 2. EPA’s Response. Proposed test note 7 also triggered the testing for 

1982 the TEP acute estuarine and marine organisms toxicity testing. EPA agrees that 

1983 the combination of “R”s, “CR”s, “NR”s and the current structure of proposed test 

1984 note 7, is confusing and that clarification is needed. 

1985 The data requirements for TEP testing and proposed test note 7 was also 

1986 considered in light of the Agency’s recent determination based on comments 

1987 received (see Unit VI.B) on EPA’s current practice of conducting risk 

1988 assessments for wood preservatives based on land-only versus a land and 

1989 aquatic predetermined use pattern. All wood preservative risk assessments will 

1990 now be performed considering that the treated wood could end-up either on the 

1991 land or in the aquatic environment. As previously discussed, there are multiple 

1992 pathways for wood preservative degradates and/or leachates to reach surface 

1993 water. EPA has also determined to conduct a down-the-drain assessment for all 

1994 appropriate use patterns which would include wood preservatives, and antifoulant 

1995 paints and coatings (see Unit XV.A). For wood preservatives, these 

1996 determinations mean that additional ecological testing is required to conduct an 

1997 ecological risk assessment, and the following changes are made to the wood 

1998 preservative testing column: 

1999  Acute freshwater invertebrates toxicity (TEP testing): change from “NR” 

2000 to “CR”; 

2001  Acute freshwater fish toxicity (TEP testing): change from “NR” to “CR”; 
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2002  Acute estuarine and marine organisms toxicity (TEP testing): change 

2003 from “NR” to “CR”. 

2004 For antifoulant paints and coatings, the determination to conduct a down2005 the-drain assessment also means that additional data could be needed for the 

2006 down-the-drain assessment, and the following changes have been made to the 

2007 antifoulant paints and coatings testing column: 

2008  Acute freshwater invertebrates toxicity (TEP testing): change from “NR” 

2009 to “CR”; 

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

2011  Acute estuarine and marine organisms toxicity (TEP testing): change 

2012 from “NR” to “CR”. 

2013 EPA believes that simplifying the data requirements that reference test 

2014 note 7 to the final Nontarget Organism Table in § 158.2240(c) so that these 

2015 requirements are CR for all use patterns is clearer, and also closer to the 

2016 suggestions made by the commenter in their suggested nontarget organism data 

2017 requirements table. Their suggested table was predominantly “CR” for aquatic 

2018 uses. Therefore, in this final rule, test note 7 triggers the “CR” studies. 

2019 However, changing all the use patterns to “CR” for the TEP studies means 

2020 changing the “R” proposed for the aquatic use, and industrial processes and water 

2021 systems use patterns for the acute freshwater invertebrates toxicity study and the 

2022 acute freshwater fish toxicity study, to “CR.” To account for this change proposed 

2023 test note 7 to the proposed nontarget organism table in § 158.2240 has been 

2024 revised to include an additional trigger (7(iv)): Data are required when “the end-
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2025 use antimicrobial product will be applied directly into an aquatic environment.” 

2026 EPA believes that the implications of this trigger are equivalent to the “R” and 

2027 essentially this is a non-change. These changes are summarized below for both 

2028 the aquatic areas and industrial processes and water systems testing column: 

2029  Acute freshwater invertebrates toxicity (TEP testing): change from “R” 

2030 to “CR”; 

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

2032  Acute estuarine and marine organisms toxicity (TEP testing): no 

2033 change. 

2034 Nontarget organism toxicity testing of the TEP should be infrequently 

2035 required for the antifoulant paints and coatings use pattern because for this use 

2036 pattern, the TEP could be the paint. Because the testing for aquatic organisms is 

2037 done in water, the test material must be soluble in water, or made soluble by 

2038 addition of an appropriate solvent, if one exists, or other appropriate mechanical 

2039 methods. Paint is not soluble and there may not be a way to make it soluble. 

2040 Since these studies are often run in glass aquaria, the paint could coat the sides 

2041 of the glass and the test animals themselves. The paint could ruin test equipment 

2042 by clogging lines and injection nozzles. Therefore EPA has added a new test 

2043 note 5, which is replacing proposed test note 5 to the proposed nontarget 

2044 organism in § 158.2240. New test note 5 to the final Nontarget Organism Table in 

2045 § 158.2240(c) states that an applicant should request a waiver if the TEP cannot 

2046 be tested. 
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2047 EPA also notes that a test note specifying the number of species to be 

2048 tested was omitted in the proposed rule for the TEP testing for acute freshwater 

2049 fish toxicity. This test note is needed for clarity. Test note 3 to the final Nontarget 

2050 Organism Table in § 158.2240(c) has been added to the line for acute freshwater 

2051 fish toxicity. 

2052 D. Acute and Chronic Toxicity Data 

2053 

2054 1. Comment. A commenter argued that it is essential to have both acute 

2055 and chronic toxicity test results for at least one freshwater invertebrate, vertebrate, 

2056 and plant species, and at least one marine/estuarine invertebrate, vertebrate, and 

2057 plant species. 

2058 2. EPA’s Response. EPA proposed to require acute tests for both a 

2059 coldwater and warmwater freshwater fish, an invertebrate, and one or more 

2060 aquatic plants. For marine/estuarine species, for most use patterns, EPA 

2061 proposed to conditionally require acute testing with a fish and two aquatic 

2062 invertebrate species, including a bivalve, when the Agency believes there is a 

2063 potential for the active ingredient or a potentially toxic degradate to reach the 

2064 estuarine/marine environment through transport (e.g., leaching, runoff) from the 

2065 treatment site. In such a situation, chronic testing with one or more 

2066 marine/estuarine species also may be required if the Agency believes that chronic 

2067 exposure is likely. These studies also are required for those uses where the 

2068 pesticide product is applied directly into the marine/estuarine environment. 

2069 As to chronic testing EPA proposed to require the fish early life stage and 

2070 the aquatic invertebrate life-cycle studies for the industrial processes and water 
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2071 systems (once-through), antifoulant coatings and paints, and aquatic areas use 

2072 patterns. At that time, EPA also proposed to conditionally require the same two 

2073 studies for the low environmental grouping (now called the all other use patterns 

2074 category) and wood preservatives. 

2075 However, based on this and other comments, EPA has re-evaluated the 

2076 nontarget organism data needed for a registration decision and concluded that 

2077 additional acute and chronic data are needed. See Units V.B, X.C, and XIV.F for 

2078 discussions on the rationale for and descriptions of the changes. 

2079 EPA does not require chronic testing for plants. Plant species encompass 

2080 many different life spans. Phytoplankton reproduce quickly and have extremely 

2081 short life spans. Annuals live for 1 year. Many perennials do not actually live for 

2082 multiple years, but reproduce from seeds year after year. The plant species that 

2083 live the longest would be woody species, such as trees. EPA does not believe 

2084 that antimicrobial use patterns impact terrestrial areas such that chronic 

2085 exposures occur: To EPA’s knowledge, no adverse chronic effects caused by 

2086 pesticides have been documented on plants. Any effect on terrestrial plant 

2087 species has been categorized as an acute effect and would be covered by current 

2088 testing procedures. Chronic effects of aquatic plants are covered by the acute 

2089 testing guidelines. Algae is used as the primary test species for the acute testing 

2090 of aquatic plants. The testing is based on growth parameters and the tests 

2091 normally run for periods of time that would include several generations of the 

2092 algae. The results from the acute algal studies would be similar to those obtained 
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2093 from chronic testing in other species, and could be used to assess any chronic 

2094 effects to aquatic plant species. 

2095 E. Avian Studies 

2096 1. Comment. In proposed test note 4 to the proposed nontarget organism 

2097 table in § 158.2240, which triggers the avian dietary study, EPA specified a trigger 

2098 of 100 mg ai/kg (milligrams active ingredient/kilogram) for additional testing. A 

2099 commenter requested information on why this trigger was selected. The 

2100 commenter also claimed that EPA could use exposure tools to conduct an initial 

2101 assessment based on Tier 1 data, and then trigger additional testing based on 

2102 risk. 

2103 2. EPA’s Response. OPP has long used this value as an indication of 

2104 toxicity to birds. As specified in 40 CFR 156.85(b)(3), any pesticide (including 

2105 conventional pesticides) that is intended for outdoor use with an avian acute oral 

2106 LD50 of 100 mg ai/kg or less requires a precautionary label statement that the 

2107 pesticide is toxic to birds. EPA believes that if 100 mg ai/kg is appropriate to 

2108 trigger a precautionary label statement, then it is also appropriate to use as a 

2109 trigger for testing. Therefore, if the avian oral acute toxicity study indicates an oral 

2110 LD50 of 100 mg ai/kg or less, then an avian dietary study is required. 

2111 In the proposed rule, for the avian dietary toxicity study, EPA proposed to 

2112 require testing on two species for the aquatic areas and to conditionally require 

2113 testing on one avian species for all of the other use patterns. The comments 

2114 reviewed and evaluated by EPA on avian toxicity testing included the 

2115 commenter’s suggested data requirements table for nontarget organisms, which 
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2116 specified “CR” for all avian testing. EPA agrees with the commenter that “CR” is 

2117 appropriate for the avian dietary toxicity and avian reproduction studies for all use 

2118 patterns. This simplifies the test notes and with the appropriate triggers EPA 

2119 would be able to require the needed testing. 

2120 The following changes have been made to the aquatic areas column: 

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

2122  Avian reproduction: change from “R” to “CR”. 

2123 Test note 4 to the final Nontarget Organism Table in § 158.2240(c) triggers 

2124 the avian dietary toxicity study based on the results of the avian acute toxicity 

2125 study. For the avian dietary study, testing in a second species would be triggered 

2126 based on the results of the avian dietary testing in the first species. Since the 

2127 second test species will be required based on the results of the first species 

2128 proposed test note 5 is no longer needed and is being removed. Test note 6 to 

2129 the final Nontarget Organism Table in § 158.2240(c) would trigger the avian 

2130 reproductive study based on one or more of four specific criteria: There were no 

2131 revisions to these criteria from the proposed rule to the final rule. 

2132 F. Water Quality Criterion 

2133 1. Comment. A commenter argued that the registrants of any 

2134 antimicrobial pesticide that has the potential to be discharged either directly or 

2135 indirectly to surface water should be required to supply any additional data 

2136 needed to derive a water quality criterion for the pesticide in question. 

2137 2. EPA’s Response. As discussed in the conventionals Response to 

2138 Comments Document in docketEPA-HQ-OPP-2004-0387 (p. 104) at 
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2139 http://www.regulations.gov, the Agency’s pesticide registration process, including 

2140 its data requirement regulations, adequately considers the endpoints that are 

2141 protected under the Clean Water Act (CWA) as administered by the Office of 

2142 Water (OW). When acceptable data are available, OPP uses these data in its risk 

2143 assessment process. 

2144 The purpose of a water quality criterion under the CWA is to determine the 

2145 level at which a water body may be at risk for environmental damage. The 

2146 purpose of certain data requirements for pesticide registration is to allow the 

2147 Agency to determine the ecological risk of using a pesticide. Thus, these program 

2148 offices within EPA have similar goals. While EPA has developed guidelines for 

2149 developing Water Quality Criteria (WQC), the Agency has also recognized that 

2150 WQC can be developed with a more limited data set. 

2151 Pesticide registration data are valuable in assessing water quality risks. As 

2152 noted in EPA’s 2005 Response to Comments Document on the conventional 

2153 pesticides, EPA’s OW and OPP together developed aquatic life benchmarks for 

2154 71 pesticides or pesticide degradation products for States to use to establish 

2155 targets for safe levels of pesticides for aquatic plants and animals. The 

2156 benchmarks are derived from data submitted to EPA for pesticide registration. As 

2157 of April 18, 2011, there are 242 pesticide chemicals with aquatic benchmarks on 

2158 EPA’s website 

2159 (http://www.epa.gov/oppefed1/ecorisk_ders/aquatic_life_benchmark.htm). 

2160 G. Sediment Testing 
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2161 1. Comment. The commenter asserted that EPA did not consider the 

2162 environmental fate of a compound (such as the tendency of a chemical to 

2163 absorb/desorb) when considering the need for sediment testing. 

2164 2. EPA’s Response. EPA disagrees with this comment. Test notes 17 and 

2165 18 to the final Nontarget Organism Table in § 158.2240(c) trigger the sediment 

2166 studies based on the results of the aerobic soil or aquatic metabolism studies and 

2167 knowledge of the physical/chemical properties which express the environmental 

2168 fate of the antimicrobial pesticide chemical. The soil partition coefficient (Kd) is 

2169 used as an expression of binding capability of the chemical to sediments. The 

2170 Agency’s justification for using Kd >50 as a criterion for requiring sediment testing 

2171 is that this value would capture those chemicals with about 80 percent adsorption 

2172 to sediments (relative to organic carbon). 

2173 The octanol-water partition coefficient (Kow) and the soil organic carbon2174 water partition coefficient (Koc) also are used by EPA as part of its decision 

2175 process. Both values are frequently more available than either the Kd or half-life 

2176 values. Test note 17, the trigger for requiring an acute sediment study, considers 

2177 all four of these values. 

2178 Next, as explained in test note 18, the chronic sediment study is triggered 

2179 based on the results of the acute sediment study as well as a re-examination of 

2180 the Kow,, Koc, and Kd . 

2181 XII. Discussion of Key Comments on Nontarget Plant Protection Data 

2182 Requirements 
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2183 The following represent the significant comments on the need for and 

2184 evaluation of nontarget plant protection studies as proposed by EPA. The 

2185 changes from the proposed rule to final rule are also described.

2186 A. Triggers for Higher-Tiered Plant Studies 

2187 1. Comment. One commenter asked EPA to explain the criteria used to 

2188 trigger higher-tiered plant studies based on the results of the algal studies. 

2189 2. EPA’s Response. The criteria to trigger higher-tiered plant studies are 

2190 specified in proposed test notes 2 and 5 to the proposed nontarget plant 

2191 protection table in § 158.2250. A toxicity level (EC50 <1 ppm) indicates that the 

2192 antimicrobial pesticide would have serious adverse affect(s) on algae at low 

2193 concentrations. This could have serious consequences to nontarget algae 

2194 species. Therefore, at this toxicity level, additional higher-tiered testing is required 

2195 to further characterize the potential adverse affects to aquatic plants. EPA is 

2196 retaining the toxicity trigger of <1 ppm in test note 5 to the final Nontarget Plant 

2197 Protection Table in § 158.2250. 

2198 In evaluating proposed test note 2 to the proposed nontarget plant 

2199 protection table in § 158.2250, EPA has considered the commenter’s suggested 

2200 table for nontarget plants. For the seedling emergence study, the commenter 

2201 used “CR” for most use patterns and suggested that the seedling emergence 

2202 study should only be required “when environmental exposure is likely to result 

2203 under normal usage conditions as determined by appropriate assessment 

2204 methods.” Another comment (see response to comment 140.27 in the Response 
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2205 to Comments Document in the docket at http://www.regulations.gov) advocated 

2206 for the use of a Risk Quotient (RQ) approach for assessing plants. 

2207 Based on this evaluation, EPA believes using “CR” for the seedling 

2208 emergence study when triggered by a level of concern approach (RQ approach) 

2209 would provide EPA with the required data when needed. Test note 2 to the final 

2210 Nontarget Plant Protection table in § 158.2250 now reads as: Data are required if 

2211 the risk quotient from any aquatic plant growth Tier II study exceeds a level of 

2212 concern for aquatic plants. 

2213 However, test note 2 also triggers the aquatic plant growth (aquatic 

2214 vascular plant) study, and is still the appropriate trigger for that study. Today, 

2215 EPA is adding a new test note 10 to the final Nontarget Plant Protection Table in § 

2216 158.2250, which will read the same as the original, proposed test note 2 to the 

2217 proposed nontarget plant protection table in proposed § 158.2250. 

2218 B. Alternative Format for Plant Protection Data Requirements Table 

2219 1. Comment. In the comments submitted to EPA, the commenters 

2220 suggested an alternate antimicrobial plant protection data requirements table. 

2221 2. EPA’s Response. The table suggested by the commenter is not adequate to evaluate the 

2222 hazards and risks to nontarget plants from antimicrobial pesticides. The suggested table did not 

2223 include test guideline numbers, changed and reduced the number of use patterns, and proposed that 

2224 all ecotoxicity plant studies are either not required or only conditionally required. The commenter 

2225 contends that there are no circumstances where ecological effects plant data are relevant for 

2226 antimicrobial pesticides, and that indoor uses should not be subject to environmental exposure or 

2227 nontarget plant species risk assessments. EPA disagrees with many aspects of these comments 

2228 and the suggested ecotoxicity data requirements table for plant species. 
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2229 As previously discussed in the preamble to the proposed rule (73 FR 59406-7) and in 

2230 Units III and V of this rule, EPA disagrees that exposure for nontarget plants should be presumed 

2231 to be minimal or nonexistent for antimicrobials applied indoors, or that tests are not required if the 

2232 test organism is the target species for the pesticide (see testnotes 1 and 2 to the commenter’s 

2233 suggested table). Moreover, there are many outdoor uses of antimicrobials that are not addressed 

2234 in the commenter’s suggested table. FIFRA mandates that EPA conduct a risk assessment for any 

2235 uses for which exposure may occur in the various environmental compartments/media. Those 

2236 risks are assessed separately for the various taxa including plants, categories (e.g., freshwater, 

2237 saltwater), and short-term (i.e., acute) and longer-term (i.e., chronic) exposures. Assessing these 

2238 potential risks necessitates having an appropriate ecotoxicity data base for plant exposure and 

2239 toxicity. This can only be accomplished by requiring plant studies for the initial assessment. A 

2240 tiered approach cannot be driven solely by risk quotients derived from a Tier 1 study. The fact that 

2241 an acute risk quotient for a plant species does not exceed a level of concern for acute risk does not 

2242 imply that a chronic risk does not exist or that data are not needed to assess that risk. The trigger 

2243 for a chronic test is more likely driven by the frequency, duration, or magnitude of the chronic 

2244 exposure and the environmental properties of the pesticide. For example, plants might be 

2245 subjected to repeated low-level exposure that is not acutely lethal but which may impact 

2246 reproductive success and plant growth. 

2247 EPA disagrees that the test substance for plant studies (in the commenter’s table) should 

2248 be identified simply as the “residue of concern (ROC).” In its proposed nontarget plant data 

2249 requirements table, EPA specified the test material (TGAI, TEP) to be used for each study. The 

2250 test substance determination is made after reviewing the required environmental fate and 

2251 physical/chemical properties data and any other available information (e.g., open literature, closely 

2252 related chemicals) to determine the substance of concern for exposure of non-target plants and 

2253 organisms. For example, if an applicant can adequately demonstrate that the TGAI dissipates so 
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2254 rapidly that there would be no acute or chronic exposure, TGAI testing may be waived, and 

2255 instead degradate testing may be required. 

2256 The commenter also omitted all guideline numbers from its suggested data table. At this 

2257 time, all data requirement tables in 40 CFR part 158 have guideline numbers since this is a method 

2258 of providing information to applicants. Applicants are not required to use these guidance 

2259 documents, but are encouraged to use these test guidelines when developing data. Since these 

2260 guidelines have been developed via a rigorous process, as discussed in the preamble to the 

2261 proposed rule [59387], “they represent the recommended approach to developing high-quality data 

2262 that should satisfy EPA’s data needs for risk assessment.” 

2263 XIII. Discussion of Key Comments on Applicator and Post-Application 

2264 Exposure Data Requirements 

2265 The following represent the significant comments received on the need for 

2266 and evaluation of applicator and post-application exposure studies as proposed 

2267 by EPA. Changes from the proposed rule to the final rule are also described. 

2268 A. Consistency With OSHA and Other Standards 

2269 1. Comment. A commenter asserted that EPA should be consistent with 

2270 OSHA and other standards with regard to exposure limits and handling practices, 

2271 and incorporate the OSHA standards into risk assessment evaluations. The 

2272 commenter also asked that when EPA believes that an OSHA or American 

2273 Conference of Governmental and Industrial Hygienists (ACGIH) standard is not 

2274 adequately protective for an antimicrobial, that the finding should be 

2275 substantiated. 

2276 2. EPA’s Response. The OSHA workplace standard is the permissible 

2277 exposure limit (PEL). When developing a PEL, OSHA considers the toxicity of the 

2278 chemical, often using data from the open literature as well as the feasibility that 
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2279 exposures could be reduced to the PEL using process modifications, engineering 

2280 controls and personal protective equipment (PPE). Approximately 500 PELs have 

2281 been established. 

2282 The ACGIH establishes health–based Threshold Limit Values (TLVs), 

2283 which are non-governmental guidelines used by professional industrial hygienists 

2284 in making decisions about safe levels of exposure to a chemical substance in the 

2285 workplace. The TLVs were established for some chemicals as early as 1946 and 

2286 they are updated on a regular basis as new health effects information becomes 

2287 available. Like the OSHA PELs, the TLVs are based on health effects data from 

2288 the open literature. However, unlike the OSHA PELs, feasiblity issues are not 

2289 considered in establishing TLVs. TLVs are not available for most pesticide 

2290 chemicals. 

2291 However, for those pesticide chemicals with both TLVs and RfCs 

2292 (Reference Concentrations are established by OPP based on studies submitted 

2293 by the registrants), the RfCs are often lower than the TLVs. There could be 

2294 several reasons for such differences. The data used by OPP is submitted by the 

2295 pesticide registrants and the toxicity database is composed of animal studies. So, 

2296 uncertainty factors are used to derive the RfCs (exposure limits). Instead of 

2297 animal studies, ACGIH prefers to rely on epidemiology studies/case reports of 

2298 human, particularly worker, exposures from the literature and on professional 

2299 judgment. 

2300 For example, ACGIH and OPP established different inhalation limits for 

2301 formaldehyde based on slightly different interpretations of the same literature 
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2302 studies. The TLV for formaldehyde is 300 ppb and the OPP “RfC” for 

2303 occupational uses is 100 ppb. Although the TLV is greater than the “RfC,” 

2304 ACGIH does acknowledge in their TLV documentation that irritation can occur in 

2305 some workers at levels of 100 to 300 ppb. 

2306 EPA believes that an existing OSHA or ACGIH standard should be 

2307 considered as part of EPA’s hazard evaluation. However, before using an OSHA 

2308 or ACGIH standard, EPA would review the standard and the health effects 

2309 (toxicology) documents supporting the standard’s development to determine if 

2310 EPA believes that the standard provides adequate protection. EPA agrees with 

2311 the commenter that EPA’s evaluation of an existing OSHA or ACGIH standard 

2312 should be part of its hazard evaluation documentation. 

2313 In its proposed rule, EPA proposed in the applicator exposure table (40 

2314 CFR 158.2260(a)(1)) and the post-application exposure table (40 CFR 

2315 158.2270(a)(1)) to use established workplace standards, such as OSHA’s. The 

2316 proposed language was: 

2317 If EPA determines that industrial standards, such as 

2318 the workplace standards set by the Occupational 

2319 Safety and Health Administration, provide adequate 

2320 protection for a particular pesticide or a particular use 

2321 pattern, applicator exposure data may not be required 

2322 for that pesticide or the use pattern. Applicants should 

2323 consult with the Agency on appropriate testing before 

2324 the initiation of studies. 

2325 

2326 In addressing this comment, EPA realized that this proposed language is 

2327 misplaced and also needs some textual modification. As discussed above, an 

2328 OSHA PEL or ACGIH standard is part of hazard evaluation. If the PEL or TLV is 

2329 determined to be adequate to fulfill EPA’s selection of a toxicity endpoint, then the 
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2330 types and number of toxicity studies that may be required is impacted, not the 

2331 need for exposure data. Therefore, EPA has removed the language originally 

2332 proposed for § 158.2260(a)(1) and § 158.2270(a)(1) concerning use of OSHA 

2333 standards. With modifications, the following language appears in the final 

2334 Toxicity Table, § 158.2230(e): 

2335 If EPA determines that industrial standards, such as 

2336 the workplace standards set by the Occupational 

2337 Safety and Health Administration, provide adequate 

2338 protection for a particular pesticide or a particular use 

2339 pattern, additional toxicity data may not be required 

2340 for that pesticide or the use pattern. 

2341 

2342 B. Poisoning Incident Data 

2343 1. Comment. “Poisoning incident data” should not be incorporated into 

2344 this regulation unless the EPA can provide criteria to trigger the need for exposure 

2345 data based on poisoning incidents. Regulating based upon anecdotal reports of 

2346 “poisoning” is not appropriate. 

2347 2. EPA’s Response. Both proposed § 158.2260(b) and § 158.2270(b) 

2348 contained the following trigger for requiring exposure data: “Scientifically sound 

2349 epidemiological or poisoning incident data indicate that adverse health effects 

2350 may have resulted from handling of the pesticide." EPA understands that 

2351 anecdotal reports may or may not indicate a cause-effect relationship, i.e., that 

2352 adverse health effects may or may not have resulted from exposure to the 

2353 pesticide. EPA agrees that anecdotal reports may not substantiate a clear dose 

2354 response relationship of “poisoning,” and therefore, when not substantiated, are 

2355 not appropriate for regulatory endpoints. In-depth information on the dose 

2356 response is the critical information needed for regulatory endpoints, and poisoning 
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2357 incident data rarely include this information. However, EPA’s intention was to use 

2358 scientifically credible information as a trigger for requiring exposure data. Based 

2359 on this comment, EPA has revised the toxicity triggers in § 158.2260 and § 

2360 158.2270 to clarify that poisoning incident data must have a clear cause effect 

2361 relationship to indicate that adverse health effects may have resulted from 

2362 exposure to the pesticide. 

2363 C. Use of Existing Post-Application Exposure Data

2364 1. Comment. A commenter argued that there is a significant amount of 

2365 post-application exposure data available that should be considered/used before 

2366 requiring data under FIFRA. 

2367 2. EPA’s Response. EPA acknowledges that there are existing exposure 

2368 data either in the literature, or via other governmental organizations such as 

2369 OSHA, or academia, etc. When available and appropriate, EPA uses such 

2370 exposure data and/or information in its risk assessments. For example, the risk 

2371 assessments for both chlorine dioxide and ethylene oxide relied heavily on the 

2372 workplace air concentration monitoring data available in OSHA’s Chemical 

2373 Exposure Health Database (CEHD), formerly known as, Integrated Management 

2374 Information System (IMIS). To access CEHD, users navigate on the OSHA 

2375 homepage (http://osha.gov/) to Chemical Exposure Health Data under the Data 

2376 and Statistics section towards the bottom right of the page. Users can search 

2377 CEHD by Establishment Name, State, Zip Code, Year Range, Standard Industrial 

2378 Classification (SIC), North American Industrial Classification System Code 
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2379 (NAICS), Chemical Abstracts Service Number (CAS), Chemical Name, or Result 

2380 Range. 

2381 Applicants who are aware of existing data that could fulfill a data 

2382 requirement should submit the data to EPA. EPA will consider the 

2383 appropriateness and robustness of the data, and, if appropriate, will use the data 

2384 in the Agency’s risk assessment. 

2385 D. Soil Residue and Indoor Surface Residue Dissipation Studies

2386 1. Comment. A commenter claimed that there is little justification for 

2387 requiring the soil residue dissipation and indoor surface residue dissipation 

2388 studies. 

2389 2. EPA’s Response. In the proposed rule, EPA conditionally required the 

2390 soil residue dissipation study for both occupational and residential scenarios. 

2391 EPA agrees that the likelihood of requiring soil residue dissipation data is low for 

2392 the majority of antimicrobial use patterns. The low likelihood is reflected in the 

2393 “CR” designation in the proposed post-application exposure data requirements 

2394 table for the soil residue dissipation study for both occupational and residential 

2395 use patterns. No changes are needed. 

2396 In the proposed rule, EPA required the indoor surface residue dissipation 

2397 study for both occupational and residential scenarios. However, the likelihood of 

2398 requiring indoor surface residue dissipation data is high for residential products 

2399 such as antimicrobial-treated clothing and plastic consumer items/toys, as well as 

2400 direct applications such as carpet shampoos, laundry detergents, and floor 
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2401 cleaners that are antimicrobial products. Therefore, the indoor surface residue 

2402 dissipation study for the residential use sites will remain “R” as proposed. 

2403 However, EPA has re-evaluated the “R” proposed for occupational use 

2404 sites. When compared to residential use sites, occupational use sites are less 

2405 likely to result in the need for indoor surface residue dissipation data. Therefore, 

2406 the data requirement for indoor surface residue data has been revised from “R” to 

2407 “CR” for occupational uses. 

2408 In most manufacturing settings, there is less contact with surfaces than in 

2409 most residential scenarios. For example, under most circumstances workers do 

2410 not crawl around the floors of manufacturing plants. The need for indoor surface 

2411 residue dissipation data for workers is limited by the residue distribution where 

2412 contact may occur. EPA now agrees that the occupational use sites are less 

2413 likely to result in the need for indoor surface residue dissipation data, and 

2414 therefore, the “R” has been revised to “CR.” 

2415 E. Non-Dietary Ingestion Study 

2416 1. Comment. A commenter asserted that the proposed requirement for 

2417 non-dietary ingestion is impractical and unnecessary, and, in fact, could be 

2418 replaced by modeling. 

2419 2. EPA’s Response. EPA agrees that the non-dietary ingestion study is 

2420 impractical, as a stand-alone direct measurement study. Non-dietary ingestion 

2421 exposure (i.e., incidental oral ingestion by children) is of potential concern for 

2422 treated articles or surfaces that may be accessed by children. For example, uses 

2423 such as carpet shampoo, hardwood floor treatments, pressure-treated wood, and 
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2424 impregnated materials (including but not limited to plastic toys or treated clothing) 

2425 are assessed for non-dietary exposures when toxicity criteria are triggered. In all 

2426 of these instances, non-dietary ingestion exposures are estimated using residue 

2427 data from the treated surface combined with activity factors for children’s 

2428 behaviors (e.g., frequency of hand-to-mouth contact). Often, EPA models this 

2429 route and pathway of exposure using inputs from the available, reliable published 

2430 research. If EPA were to require data to estimate this exposure pathway, EPA 

2431 would require surface residue data, rather than requiring the actual monitoring of 

2432 children or having individual registrants collecting data on frequency of hand-to2433 mouth activities, as these are not chemical-specific. Given the unlikelihood of 

2434 requiring non-dietary ingestion exposure studies, EPA has removed this data 

2435 requirement from the final Post-Application Exposure Table as well as the 

2436 accompanying test note 12. 

2437 XIV. Discussion of Key Comments on Environmental Fate Data 

2438 Requirements 

2439 The following represent the significant comments received on the need for 

2440 and evaluation of environmental fate studies as proposed by EPA. Changes from 

2441 the proposed rule to the final rule are also described. 

2442 A. Need for Environmental Fate Data for Indoor Uses 

2443 1. Comment. Several commenters argued that the proposed 

2444 environmental fate data requirements for indoor uses of antimicrobials should not 

2445 exceed those in part 158 for conventional pesticide chemicals, since 

2446 antimicrobials are not directly broadcast into the environment. 
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2447 2. EPA’s Response. As explained in the proposed rule, there is now a 

2448 greater concern regarding indoor uses of antimicrobials because those 

2449 antimicrobial uses can lead to environmental exposure when they go down-the2450 drain. The rationale for requiring environmental fate data for antimicrobials 

2451 mirrors that of Unit XI.A for requiring nontarget organism data for antimicrobials. 

2452 There are many uses for which a high potential for exposure exists, and 

2453 these uses may require a more extensive environmental fate data set that could 

2454 also include aerobic and anaerobic metabolism studies. However, such uses will 

2455 typically require a much reduced first tier data set with additional testing triggered 

2456 if the results of the required data indicate a potential risk that needs further 

2457 characterization. 

2458 B. Transformation Products 

2459 1. Comment. A commenter argued that the Agency has not clearly stated 

2460 when environmental fate data on the transformation products would be required. 

2461 Additionally, the commenter also wanted to understand the data that would be 

2462 required if the substance degrades quickly? 

2463 2. EPA’s Response. For environmental fate data, the Agency evaluates 

2464 transformation products on a case-by-case basis, using several sources of 

2465 information. First, the transformation products need to be identified. While 

2466 product chemistry data can provide some information on degradates, 

2467 environmental fate data provide data specific to a particular environmental 

2468 compartment. Environmental fate studies provide information on the stability and 

2469 persistence of the active ingredient and its degradation products in the various 
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2470 environmental media. For example, in the hydrolysis study, a half-life >30 days 

2471 indicates that the substance is stable to hydrolytic processes, i.e., the substance 

2472 did not degrade. Similar determinations are made based on the results of the 

2473 photodegradation in soil and water studies, and the aerobic and anaerobic 

2474 metabolism in soil and water studies after review of the required fate data. 

2475 Monitoring and incident data, if available, also may indicate stability and 

2476 persistence. There could also be environmental fate data conducted on a related 

2477 chemical or information from the open literature. This analysis is critical to 

2478 determining not only the need for environmental fate data for transformation 

2479 products, but also is the first step for determining the need for nontarget organism 

2480 or nontarget plant data for transformation products. 

2481 EPA proposed criteria to require testing of transformation/degradation 

2482 products or leachate residues in proposed § 158.2280(a)(2) and (3). To respond 

2483 to this comment, EPA also considered a similar comment on 

2484 transformation/degradation products or leachate residues for nontarget plant and 

2485 organism testing (see Unit XI.B). In response to these comments, EPA 

2486 determined to clarify and revise the criteria for testing of 

2487 transformation/degradation products and leachate residues for nontarget plant 

2488 and organisms, and environmental fate, (§ 158.2250(b), 158.2240(a)(3), and 

2489 158.2280(a)(2)) to read as follows: 

2490 Data on transformation/degradation products or 

2491 leachate residues of the parent compound are also 

2492 required to support registration, if the Agency 

2493 determines that the 

2494 transformation/degradation/leachate products meet 

2495 one of the following criteria: 
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2496 (i) More toxic, persistent, or bioaccumulative than the 

2497 parent, 

2498 (ii) Have been shown to cause adverse effects in 

2499 mammalian or aquatic reproductive studies, or 

2500 (iii) The moiety of concern (i.e., functional group in the 

2501 parent chemical molecule that imparts adverse 

2502 effects) remains intact. 

2503 

2504 EPA would use these criteria to determine if environmental fate data on the 

2505 transformation/degradation products or leachate residues are required. 

2506 Therefore, if the environmental fate studies on the parent indicate the 

2507 transformation product(s) is, for example, more persistent in soils, then the same 

2508 environmental fate data required for the parent are required for the transformation 

2509 product(s). If concerns are identified, then higher-tiered environmental fate and/or 

2510 ecological effects data on the transformation/degradation product(s) would be 

2511 required. 

2512 It should be noted that the criteria for determining whether to assess risks 

2513 from a chemical substance and/or its degradation products when conducting a 

2514 down-the-drain analysis are different from those discussed above. Those criteria 

2515 are discussed in response to comment 130.4 in the Response to Comments 

2516 Document in the docket at http://www.regulations.gov. 

2517 C. Photodegradation in Soil Study

2518 1. Comment. A commenter claimed that EPA has not sufficiently 

2519 explained why a photodegradation in soil study would be required if a substance 

2520 hydrolyzes and its behavior is known from its soil profile. 

2521 2. EPA’s Response. EPA proposed to require the photodegradation in soil 

2522 study for only one use pattern: wood preservatives. Wood products that have 
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2523 been treated with wood preservatives are often in contact with soil, and therefore 

2524 it is possible for the wood preservative chemical, as well as its transformation and 

2525 degradation products, to leach out from the treated wood product. To understand 

2526 the fate of wood preservative chemicals in soil, first requires an understanding of 

2527 the soils properties. Soil profiles are descriptions of soil properties, both physical 

2528 and chemical. Examples of physical characteristics would include: color, bulk 

2529 density, and texture. Examples of chemical characteristics would include: pH of 

2530 the soil, organic matter content, and Cation Exchange Capacity (CEC). 

2531 Depending on the soil profile, an antimicrobial pesticide can undergo chemical 

2532 and/or biochemical (biodegradation) processes. For example, if the pH of the soil 

2533 is less than 7, the antimicrobial can undergo hydrolysis and become 

2534 nonpersistent, or if the pH of the soil is basic, the antimicrobial could remain 

2535 stable and become persistent. If the organic carbon content of a soil is high, then 

2536 the soil has a high microbial population which facilitates the biodegradation 

2537 process. Hence the nature of a soil (soil profile) is an important indicator of how a 

2538 pesticide may behave in a soil. 

2539 Many applicants are well aware of soil profiles, since EPA asks for the soil 

2540 profile to be submitted along with the results of the studies in soils. A number of 

2541 soil profile databases are available: Two of the databases used by OPP are one 

2542 from USDA and one called CLARION. 

2543 In this final rule, EPA has retained the requirement for a photodegradation 

2544 in soil study for the wood preservatives use pattern. If data from the standardized 

2545 soil profiles show that the chemical is likely to readily degrade microbially or 
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2546 undergo redox reactions (degrade chemically), then the photodegradation study in 

2547 soils may not be required. EPA is adding a new test note 10 to replace proposed 

2548 test note 10 to the proposed environmental fate table in § 158.2280. New test 

2549 note 10 to the final Environmental Fate Table in § 158.2280(c) explains this 

2550 condition for not requiring the photodegradation in soil study. 

2551 D. Aquatic Sediment Study 

2552 1. Comment. A commenter claimed that EPA is unclear about the triggers 

2553 that would lead to the requirement for an aquatic sediment study, and how down2554 the-drain (D-t-D) modeling could affect the need for this study. 

2555 2. EPA’s Response. Proposed test notes 5 and 13 to the proposed 

2556 environmental fate table in § 158.2280 trigger the aquatic sediment study for all 

2557 use patterns except the aquatic areas use pattern. EPA has re-evaluated the 

2558 need for the aquatic sediment study and the appropriate triggers. EPA agrees 

2559 that having two triggers, both of which use a weight-of-evidence evaluation 

2560 process, is confusing, and believes that one trigger (proposed test note 13) would 

2561 be sufficient for triggering the aquatic sediment study. In today’s action, EPA is 

2562 removing test note 5 from the test note column for the aquatic sediment study 

2563 data requirement. Based on this re-evaluation, EPA also believes that the aquatic 

2564 sediment study should be required for the antifoulant coatings and paints use 

2565 pattern since an antifoulant use would meet the criteria of the trigger in test note 

2566 13, which is: “...data are required based on the potential for aquatic exposure 

2567 and if the weight-of-evidence indicates that the active ingredient or principal 

2568 transformation products are likely to have the potential for persistence, mobility, 
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2569 nontarget aquatic toxicity, or bioaccumulation.” Antifoulants are released/applied 

2570 directly to the aquatic environment. These products are often manufactured to be 

2571 persistent, and because of the continuous release process, some of the active 

2572 ingredient is likely to be transferred to the bottom of the water column and then be 

2573 adsorbed to the sediment. This is likely to result in adverse effects on nontarget 

2574 benthic organisms. Since this meets the triggers for requiring the study, today 

2575 EPA is changing the “CR” for the aquatic sediment study for the antifoulant 

2576 coatings and paints use pattern to “R.” 

2577 The aquatic sediment study provides information about the 

2578 degradation/dissipation processes under field conditions. The results of D-t-D 

2579 modeling are unlikely to provide appropriate information to determine the need for 

2580 the aquatic sediment study. The current version of the D-t-D model estimates 

2581 concentrations of chemical substances in the water column downstream of 

2582 wastewater treatment facilities, but does not estimate concentrations in the 

2583 sediment. 

2584 G. Monitoring of Representative U.S. Waters Study.

2585 1. Comment. The commenter noted that there is no guidance on how to 

2586 conduct a “monitoring of representative US waters” study, and that EPA has not 

2587 provided the criteria for triggering a “monitoring of representative U.S. waters” 

2588 study. 

2589 2. EPA’s Response. The commenter is correct: EPA does not have a 

2590 guideline for conducting this study. For all pesticides, such monitoring (studies) of 

2591 representative U.S. waters is a very rare occurrence. If EPA were to require such 
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2592 a monitoring study, protocols would have to be developed to specify a great deal 

2593 of information: 

2594  At which locations would the monitoring occur, and how often would 

2595 the monitoring occur? 

2596  Is the sampling for ground water, surface water, or the 

2597 estuarine/marine environment? 

2598  Which chemical substances would be monitored? Is just the 

2599 antimicrobial (parent) to be analyzed, or would the transformation/degradation 

2600 products also be analyzed? Such a protocol would be specific to a particular 

2601 pesticide, where that pesticide is used, and where the pesticide has been 

2602 detected, and could not necessarily be used for a different pesticide. 

2603 For the monitoring of representative U.S. waters data requirement, the term 

2604 “residue of concern” (ROC) is currently specified in the Environmental Fate Data 

2605 Requirements Table in the test substance to support column. Since the ROC 

2606 would be determined during protocol development, EPA is adding this information 

2607 as part of a new test note 17 to the final Environmental Fate Table in § 158.2280. 

2608 As stated in the preamble to the proposed rule, a WOE approach would be 

2609 used to determine if a monitoring of representative U.S. waters study should 

2610 required. The preamble to the proposed rule discusses this aspect in more detail 

2611 (73 FR 59413). EPA expects this study to be rarely required. 

2612 H. AWPA and ASTM Methods 

2613 1. Comment. A commenter argued that AWPA method E11-97 or E20-04, 

2614 and ASTM Method D5108-90 “are of limited or no relevance to estimating 
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2615 environmental exposures” for wood preservatives, or antifoulants, respectively. 

2616 According to the commenter, the results of the ASTM method are not suitable for 

2617 “estimating release rates for regulation purposes.” The commenter believes that 

2618 both methods “overestimate leach rates and are not intended for use in risk 

2619 assessments.” The commenter also provided information to indicate that ASTM 

2620 Method D5108-90 has been replaced by ASTM D6442-06. 

2621 2. EPA’s Response. Proposed test note 15 to the proposed environmental 

2622 fate table in § 158.2280 triggers the special leaching data requirement for the 

2623 wood preservative use pattern. EPA’s intent in specifying that it would accept an 

2624 ASTM or AWPA method was to allow applicants to use these readily available 

2625 protocols. However, as noted in the proposed testnote, protocol review was still 

2626 required for some of these methods. Since the commenters believe that these 

2627 AWPA methods are inappropriate, but have not offered alternative methods, test 

2628 note 15 to the final Environmental Fate Table in § 158.2280(c) is revised to 

2629 remove the AWPA methods. Test note 12 to the final Environmental Fate Table 

2630 in § 158.2280(c) is added to require protocol review. 

2631 Test note 16 to the proposed environmental fate table in § 158.2280 

2632 triggers the special leaching data requirement for the antifoulant coatings and 

2633 paints. Since the commenter indicated that the ASTM method has been 

2634 replaced, EPA believes that specifying an ASTM method number in regulatory 

2635 text may provide insufficient clarity, at some point in the future. Therefore, test 

2636 note 16 to the final Environmental Fate Table in § 158.2280 is revised to remove 
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2637 the ASTM methods. Test note 12 to the final Environmental Fate Table in § 

2638 158.2280(c) is added to require protocol review. 

2639 XV. Discussion of Key Comments on Down-the-Drain Analysis 

2640 The following represent the significant comments received on the need for 

2641 and performance of a Down-the-Drain analysis as proposed by EPA. Changes 

2642 from the proposed rule to the final rule are also described.

2643 A. Changes to Down-the-Drain Analysis Based on Comments Received 

2644 1. Comment. Some commenters expressed concern regarding EPA’s 

2645 proposal to exclude antifoulants and wood preservatives from testing designed to 

2646 protect POTWs and the aquatic environment. These commenters contend that 

2647 these compounds may reach POTWs through sources such as hull blast water, 

2648 landfill leachate, and centralized waste treatment facilities. They think EPA 

2649 should revisit this assumption to verify its accuracy. 

2650 2. EPA’s Response. Based on this comment, EPA did re-evaluate its 

2651 original determination to exclude antifoulant coating and paints, wood 

2652 preservatives, and aquatic areas from down-the-drain analysis. EPA still believes 

2653 that it is appropriate to exclude aquatic areas from a down-the-drain analysis. As 

2654 discussed in the preamble (73 FR 59390) aquatic areas include lakes, ponds, 

2655 streams, drainage ditches, and other bodies of water. These would not be 

2656 expected to result in down-the-drain releases and are therefore unlikely to be 

2657 discharged to a WWTP. 

2658 Based on its re-evaluation, EPA believes that a down-the-drain analysis is 

2659 needed for the wood preservative, and antifoulant paints and coatings use 
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2660 patterns, as well as the all other use patterns category. There are a number of 

2661 sources of indirect releases of antifoulants and wood preservatives to surface 

2662 water via WWTPs. The Emission Scenario Document (ESD) for Wood 

2663 Preservatives, which is part of the OECD Series on Emission Scenario 

2664 Documents, documents numerous sources of environmental releases directly to 

2665 surface water. The ESD also describes various types of wood preservative 

2666 facilities where there may be environmental releases to the facility drain that 

2667 subsequently drains to a WWTP. Some of the types of wood preservative facilities 

2668 identified in the OECD ESD for wood preservatives include automated spraying 

2669 plants, dipping/immersion plants, and plants that employ vacuum-pressure and 

2670 double vacuum processes. According to this OECD ESD for wood preservatives, 

2671 it is also possible for releases to sewage treatment plants to occur from some 

2672 treated wood products, such as noise barriers. 

2673 According to the OECD Emission Scenario Document for Antifouling 

2674 Products, in addition to the numerous sources of direct environmental releases to 

2675 surface water resulting from the use of antifoulant paints and coatings, there is the 

2676 potential for antifoulants to enter sewage treatment plants as a result of 

2677 application and removal of antifoulant paints at boatyards and marinas. 

2678 Thus, OPP’s Antimicrobial Division (AD) will perform a down-the-drain 

2679 assessment for every product with an applicable use or exposure scenario that 

2680 has the potential for waters containing antimicrobials to reach a WWTP. To 

2681 perform this assessment, the Agency is requiring data on the biodegradation of an 

2682 antimicrobial pesticide and its potential toxicity to WWTP microorganisms in an 
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2683 activated sludge basin. For some antimicrobial pesticides, the Agency will also 

2684 require the activated sludge sorption isotherm test to determine removal from 

2685 wastewater via partitioning to activated sludge. For additional information on the 

2686 changes made to the proposed environmental fate data requirements table see 

2687 response to comment 134.1 in the Response to Comments Document in the 

2688 docket at http://www.regulations.gov.

2689 B. Use of E-FAST Model 

2690 1. Comment. According to one commenter, EPA staff indicated at the 

2691 part 158, subpart W Antimicrobials Data Requirements Workshop held on 

2692 November 6, 2008 that the E-FAST model may have been based on municipal 

2693 WWTPs that received only “residential” discharges. The commenter suggested 

2694 that is very unlikely and stated that according to the E-FAST manual, the model 

2695 was based on data from actual U.S. municipal WWTPs. Nearly every municipal 

2696 WWTP receives discharges from many types of non-residential sources, like 

2697 commercial facilities, medical facilities, institutions, and cooling water systems 

2698 (which are common in commercial buildings). Even in smaller communities, 

2699 POTWs receive wastewater from residential and commercial (e.g., schools, 

2700 stores, restaurants, hotels/motels, and/or medical facilities) sources. Most 

2701 municipal WWTPs also receive both process and non-process discharges from 

2702 industrial facilities. Some commenters contend that the E-FAST model is 

2703 applicable as a screening-level model for all antimicrobial use patterns with 

2704 discharges that are typically rinsed down-the-drain including agricultural premises 

2705 and equipment, food handling/storage establishments, residential and public 
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2706 access premises, medical premises and equipment, industrial processes and 

2707 water systems, swimming pools, and others. 

2708 2. EPA’s Response. The E-FAST documentation manual indicates 

2709 that the down-the-drain module was developed as a screening-level model for 

2710 estimating concentrations of chemicals in surface water that may result from the 

2711 disposal of consumer products into household wastewater. The model 

2712 developers have confirmed, however, that the database of WWTPs that is 

2713 accessed by this module consists of domestic WWTPs that receive wastewaters 

2714 predominantly from residential, commercial, and institutional sources, and not 

2715 solely from residential sources. In modeling releases of antimicrobial pesticides to 

2716 environmental media, the appropriate data inputs, methods, and tools are 

2717 dependent upon the source of the environmental releases. To assess exposures 

2718 and risks to releases of antimicrobial pesticides to surface water from residential, 

2719 commercial, and institutional sources, the down-the-drain module of E-FAST is 

2720 the most appropriate tool. 

2721 To assess exposures and risks to antimicrobial pesticides from 

2722 manufacturing, processing, and industrial use facilities, the general population and 

2723 ecological exposures from the industrial releases module of E-FAST is the most 

2724 appropriate tool. The decision to use the general population and ecological 

2725 exposures from the industrial releases module is made on a case-by-case basis 

2726 considering the availability of data required as inputs to the module, and the 

2727 potential for significant exposure. For example, a low volume use may not require 

2728 use of this module. 
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2729 EPA agrees that the E-FAST model is applicable as a screening-level 

2730 model for all antimicrobial use patterns with discharges that are typically rinsed 

2731 down-the-drain including agricultural premises and equipment, food 

2732 handling/storage establishments, residential and public access premises, medical 

2733 premises and equipment, industrial processes and water systems, swimming 

2734 pools, and others. 

2735 C. Exceedance Levels

2736 1. Comment. Some commenters questioned the justification for the 

2737 following exceedance levels that were used by EPA to evaluate potential risks to 

2738 aquatic organisms: 

2739 i. Potential risks from effects to aquatic invertebrates and fish: Exceedance 

2740 of the chronic concentration of concern (COC) for 20 or more days triggers a 

2741 potential for concern; 

2742 ii. Potential risks from effects to aquatic invertebrates and fish: 

2743 Exceedance of the acute COC for 4 or more days triggers a potential for concern; 

2744 and 

2745 iii. Potential risks from effects to algae: Exceedance of the COC for algae 

2746 for 4 days or less may trigger a concern and is evaluated on a case-by-case 

2747 basis. 

2748 2. EPA’s Response. These exceedance levels and corresponding 

2749 number of days of exceedance that trigger potential for concern are those cited on 

2750 page 7-7 of EPA/OPPTS/OPPT’s “Revised Draft New Chemicals Decision 

2751 Guidelines Manual” dated April 17, 2001. The justification that the potential for 
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2752 chronic risk to aquatic organisms may exist if the predicted environmental 

2753 concentration (PEC) exceeds the chronic COC and the exceedance occurs for 20 

2754 days or more per year is documented on page 11 of “Interpretive Assistance for 

2755 Sustainable Futures Summary Assessment,” updated January 22, 2007: 

2756 “...although there is a potential for the concentration 

2757 of the chemical in the water to reach levels exceeding 

2758 the hazardous level, the levels are not exceeded for a 

2759 sufficient duration of time to induce any chronic 

2760 effects. The 20-day criterion is derived from partial 

2761 life-cycle tests (daphnid chronic and fish early life2762 stage tests) that typically range from 21 to 28 days in 

2763 duration. Low concern for chronic risk exists if the 

2764 COC is exceeded on fewer than 20 days per year or 

2765 the PEC is less than the chronic COC.” 

2766 

2767 EPA notes that risk is influenced by both the duration of exposure and the 

2768 likelihood of that exposure occurring. Often mathematical models are used to 

2769 estimate exposures and risks. There are two types of models: deterministic or 

2770 probabilistic. Probabilistic modeling is a technique that utilizes the entire range of 

2771 input data to develop a probability distribution of risk or exposure rather than a 

2772 single point value. The analysis identifies the probability that the exposure 

2773 exceeds the COC and for what timeframe. Deterministic modeling is based on 

2774 select input data that result in a single point estimate. The estimate either 

2775 exceeds or does not exceed the COC. Models such as E-FAST have the 

2776 capability of providing either deterministic or probabilistic results. Consequently, 

2777 criteria for determining whether or not testing on aquatic organisms is required 

2778 need to take into account the possibility that the estimated exposure could be 

2779 modeled using either deterministic or probabilistic modeling. Therefore, two test 
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2780 notes to the final Nontarget Organism Table in § 158.2250 have been revised to 

2781 include a probabilistic trigger for down-the-drain analyses, while retaining the 

2782 existing deterministic trigger for releases of antimicrobials that are expected to 

2783 enter WWTPs. Test note 7 to the final Nontarget Organism Table in § 158.2250(c) 

2784 triggers the acute freshwater invertebrate toxicity study (TEP testing) and the 

2785 acute freshwater fish toxicity study (TEP testing). Test note 12 to the final 

2786 Nontarget Organism Table in § 158.2250(c) triggers the fish life-cycle study.

2787 D. Evaluation of Discharges to Still Water and to Salt Water 

2788 1. Comment. During the Antimicrobial Data Requirements Workshop held 

2789 on November 6, 2008, EPA staff indicated that evaluation of discharges to still 

2790 water and to salt water would be challenging. The commenter’s argued that the 

2791 E-FAST model manual suggests that these discharges can be readily evaluated 

2792 with appropriate input data and elimination of the PDM (Probabilistic Dilution 

2793 Model) option. 

2794 2. EPA’s Response. EPA believes that the commenter misunderstood the 

2795 context of the Information provided by EPA staff both in the proposed rule and at 

2796 the presentation on November 6, 2008. E-FAST has two modules for estimating 

2797 releases to surface water: The down-the-drain module, and the general 

2798 population and ecological exposure from industrial releases module. 

2799 When the down-the-drain module of E-FAST is run without the PDM option, 

2800 the results are limited to estimates of concentrations in surface water downstream 

2801 of domestic wastewater treatment facilities. The down-the-drain module has no 

2802 option for estimating concentrations in non-flowing waterbodies such as lakes, 
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2803 bays, estuaries, and oceans. The discussion at the November 6, 2008, Workshop 

2804 focused solely on the down-the-drain module. 

2805 E-FAST, however, has the capability for evaluating discharges to still water 

2806 and to salt water from discharges to WWTPs that receive manufacturing, 

2807 processing, and industrial use releases, but not from discharges to surface water 

2808 via domestic WWTPs. The general population and ecological exposure from 

2809 industrial releases module is designed to estimate releases to air, water, and land 

2810 from manufacturing, processing, and industrial use of chemical substances. The 

2811 database for estimating releases to WWTPs that primarily receive wastewater 

2812 from manufacturing, processing, and industrial uses requires estimates of 

2813 releases to environmental media from models such as ChemSTEER (Chemical 

2814 Screening Tool for Exposures and Environmental Releases), a model developed 

2815 by EPA’s OPPT or from data and calculations included in standard scenarios, also 

2816 developed by OPPT (www.epa.gov/oppt/exposure/pubs/chemsteerdl.htm). The 

2817 general population and ecological exposure from industrial releases module 

2818 includes an option for estimating concentrations in lakes, bays, estuaries, and 

2819 oceans. 

2820 E. Parameters for Down-the-Drain Analysis 

2821 1. Comment. Several commenter’s argued that EPA’s approach for down2822 the-drain chemicals separates the exposure and the effects of the assessment 

2823 and subjects chemicals to similar testing requirements regardless of the mass of 

2824 chemicals disposed in the environment. According to these commenters, the fact 

2825 that EPA does not guide testing by the extent of environmental exposure is 
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2826 wasteful for ingredients which will reach the environment at low levels. Even for 

2827 chemicals which are used at greater volume, the commenters claimed that there 

2828 is no proof that EPA’s program will achieve its goal without being wasteful and 

2829 some commenters believe that EPA’s approach will likely result in significant 

2830 unwarranted costs in animals, time, and dollars. The commenters asserted that 

2831 this will result in unnecessary loss of animals, increased costs to the consumer 

2832 and will negatively affect product innovation as new product development will be 

2833 slowed due to the extra regulatory burden. The benefit to the environment of the 

2834 EPA approach, according to the commenters, is likely to be small and not 

2835 commensurate with its costs. 

2836 2. EPA’s Response. EPA disagrees with this comment. Three key input 

2837 parameters for the Down-the-Drain model are: 

2838 i. Percent removal of antimicrobial pesticide during wastewater treatment; 

2839 ii. Concentrations of concern for antimicrobial pesticides based on acute 

2840 and chronic end-points for freshwater fish, freshwater invertebrates, and 

2841 freshwater plants; and 

2842 iii. Wastewater treatment plant influent volume of antimicrobial pesticide. 

2843 As demonstrated in the sensitivity analysis of the down-the-drain model in 

2844 the document, “Four Case Studies of Antimicrobial Pesticides in the Down-the2845 Drain Screening Model, Using the Proposed Approach for a Screening-Level 

2846 Environmental Fate Assessment” (available in the docket at 

2847 http://www.regulations.gov), the amount of chemical disposed in the environment 

2848 strongly influences the results of the down-the-drain model. It is possible that if 
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2849 the amount of chemical disposed is small (i.e., WWTP influent volume is low 

2850 and/or high percent removal during wastewater treatment), that the predicted 

2851 surface water concentration of the antimicrobial, even for a chemical of high 

2852 toxicity, would not exceed the Agency’s level of concern. Under such 

2853 circumstances, higher-tier testing (environmental fate, ecotoxicity, and plant 

2854 protection) is unlikely to be triggered. Since, higher-tier testing is triggered only if 

2855 the down-the-drain model indicates that the predicted concentration of the 

2856 antimicrobial may adversely affect aquatic organisms this reduces the number of 

2857 tests required, and therefore the animals, time, and dollars. 

2858 EPA also notes that two of the three key input parameters needed to run 

2859 the down-the-drain model, percent removal during wastewater treatment and 

2860 wastewater treatment plant influent volume do not involve animal testing and 

2861 would not lead to loss of animals. Fate tests required to determine removal during 

2862 wastewater treatment via biodegradation and adsorption are inexpensive. No 

2863 costs are associated with wastewater treatment plan influent volume. 

2864 F. Acute and Chronic Toxicity Endpoints 

2865 1. Comment. At the Antimicrobial Data Requirements Workshop held on 

2866 November 6, 2008, EPA staff indicated that chronic aquatic toxicity endpoints 

2867 might not be used to evaluate antimicrobial discharges from municipal WWTPs. A 

2868 commenter argued that since EPA/OW requires municipal WWTP to conduct both 

2869 acute and chronic toxicity tests regularly as conditions of CWA-regulated National 

2870 Pollution Discharge Elimination System (NPDES) permits, both acute and chronic 
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2871 endpoints should be evaluated by EPA/OPP to ensure that antimicrobial 

2872 discharges will not cause toxicity in municipal WWTP effluent. 

2873 2. EPA’s Response. To assess whether the proposed screening level 

2874 assessment and tiered system of data requirements provides the data needed to 

2875 assess exposure and risk of antimicrobial pesticides released to the environment 

2876 via down-the-drain use patterns, the Agency conducted four case studies (73 FR 

2877 59408-9). Based on this comment, EPA has re-evaluated the approach used for 

2878 the case studies, in which the higher-tiered data was triggered based on the 

2879 results of the available data. To ensure that antimicrobial discharges will not 

2880 cause toxicity to aquatic organisms downstream of WWTP effluents requires an 

2881 evaluation of both acute and chronic toxicity endpoints. This means that the 

2882 chronic ecotoxicity data needs to be submitted at the same time as the acute 

2883 ecotoxicity data, so both types of studies are available for EPA to use for the 

2884 ecological risk assessment. Also see Units XV.A and B. 

2885 Consequently, in the final Nontarget Organism Table in § 158.2250(c), the 

2886 table descriptors for the fish early-life stage and aquatic invertebrate life cycle 

2887 tests have been changed from “CR” to “R” for the wood preservatives use pattern 

2888 and the all other use patterns category. Test note 10 to the final Nontarget 

2889 Organism Table in § 158.2250(c) has been modified to remove the trigger since it 

2890 is no longer needed. 

2891 XVI. Discussion of Key Comments on Residue Chemistry Data 

2892 Requirements
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2893 The following represent the significant comments received on the need for 

2894 and evaluation of residue chemistry studies as proposed by EPA. Changes from 

2895 the proposed rule to the final rule are also described. 

2896 A. Scope of the Residue Chemistry Data Requirements 

2897 1. Comment. Several commenters found the scope of coverage of the 

2898 residue data requirements in § 158.2290(b) to be vague and confusing. Further, 

2899 the ACC Biocides Panel asserted that this section required data for uses for which 

2900 a FFDCA section 408 tolerance is not required and over which, therefore, EPA 

2901 allegedly has no jurisdiction. 

2902 2. EPA’s Response. EPA is clarifying § 158.2290(b) which pertains to the 

2903 scope of the residue data requirements. That section can be read as limiting the 

2904 residue chemistry data requirements to pesticide products requiring a tolerance or 

2905 tolerance exemption. This apparent limitation is inconsistent with both the 

2906 preamble’s general description of the scope this subpart and the preamble’s 

2907 description of the scope of the residue data requirements section, and is internally 

2908 inconsistent with the terms of § 158.2290(b). Various commentators noted the 

2909 lack of clarity in this portion of the rule. 

2910 The preamble’s general discussion of the scope of subpart W made clear 

2911 that this subpart was not limited to “antimicrobial pesticides” as defined by FIFRA 

2912 section 2(mm) – which excluded antimicrobial pesticide uses subject to either 

2913 FFDCA section 408 or section 409 – but xtended to among other things, 

2914 “[p]esticide products for antimicrobial use in/on food” (73 FR 59385). In no way, 

2915 however, did this discussion suggest or imply that the subpart is limited to 
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2916 antimicrobial uses requiring FFDCA section 408 tolerances or exemptions from 

2917 tolerances. To the contrary, the preamble’s discussion of toxicity data 

2918 requirements expressly notes that data are needed under subpart W to assess 

2919 dietary risk whether or not a section 408 tolerance is required. The preamble 

2920 specifically states that, although certain antimicrobial food uses are regulated 

2921 under the FFDCA by FDA under section 409 and not section 408, EPA still needs 

2922 data on these uses to assess dietary risk to fulfill its statutory obligations under 

2923 FIFRA section 2(bb)(2), which establishes the FFDCA section 408 safety standard 

2924 as a component of the FIFRA standard for registration/cancellation for FIFRA 

2925 pesticide uses that result in residues on food (73 FR 59394). Further, the 

2926 preamble’s discussion of residue chemistry data requirements states that these 

2927 data are needed for “direct and indirect food uses” including application to “food or 

2928 water” both to assess risk and for tolerance-setting purposes (73 FR 59401: “In 

2929 addition to dietary risk assessments, residue chemistry data are used to establish 

2930 pesticide tolerance . . . .”). Finally, both the preamble’s discussion of residue data 

2931 requirements and the relevant rule text mention antimicrobial uses that would be 

2932 excluded by a limitation of the rule to antimicrobial uses requiring tolerances. For 

2933 example, both the preamble and rule text refer to “fruit and vegetable rinses,” 

2934 antimicrobials “incorporated into a material that may contact food or feed,” and 

2935 “[a]quatic uses that have the potential to result in residues in potable water” and 

2936 all of these uses may not need section 408 tolerances (73 FR 59401 and 59444). 

2937 Accordingly, EPA is revising § 158.2290(b) to make clear it is not limited to 

2938 antimicrobial uses which need FFDCA section 408 tolerances. With some 
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2939 modifications, EPA is retaining in § 158.2290(b) a non-exclusive list identifying 

2940 examples of antimicrobial products covered by this section. This revision to § 

2941 158.2290(b) makes clear that the residue data requirements apply to antimicrobial 

2942 products that may result in residues in food or water whether or not a FFDCA 

2943 section 408 tolerance is needed. Section 158.2290(b) is revised by replacing the 

2944 opening lines of subsection (b)(1) with the following: 

2945 “Residue chemistry data are required for: 

2946 (1) Antimicrobial end-use products with uses that may result in 

2947 residues in or on food including, but not limited to:” 

2948 The first item in the list of covered uses now reads “Products that require a 

2949 tolerance, tolerance exemption, or food additive regulation or clearance.” The 

2950 insertion of the reference to food additive regulations and clearances is consistent 

2951 with the rule’s scope which is not limited to pesticide uses regulated under FFDCA 

2952 section 408. Additionally, each of the subparagraphs listing examples of covered 

2953 uses has been revised to refer to “products” rather than “uses” for consistency 

2954 and clarity. Although the subparagraphs are overlapping (i.e., a product may fall 

2955 in more than one paragraph), the revised subsection now clarifies the overall 

2956 scope of this section. These revisions make § 158.2290(b) consistent with the 

2957 scope of the rule described in the preamble and the scope of the toxicology data 

2958 requirements. 

2959 Not only are these changes consistent with the scope of the rule as 

2960 discussed in the preamble (i.e. data requirements are not limited to uses needing 

2961 section 408 tolerances) but the revised language’s focus on whether use of a 
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2962 pesticide may result in residues in or on food follows directly from the intent of the 

2963 residue chemistry requirements as discussed in the preamble. There, EPA 

2964 explained that the proposed requirements will provide information “to better 

2965 estimate human dietary exposure to antimicrobial residues in or on food or feed,” 

2966 “to determine the composition of the pesticide residue and how much of the 

2967 residue is present in food or animal feed,” and to “measure how much of the 

2968 residue of concern is present in food, feed, and water” (73 FR 59401). Further, 

2969 the revised language is consistent with scope of FFDCA section 408 (applies to 

2970 “pesticide chemical residue[s] in or on food”) and FIFRA (requires consideration of 

2971 “residues that result from the use of a pesticide in or on food”). It also follows 

2972 directly from the existing data requirements applying to antimicrobials in Part 161. 

2973 Those regulations provide that “Residue Chemistry Data are used by the Agency 

2974 to estimate the exposure of the general population to pesticide residues in food 

2975 and for setting and enforcing tolerances for pesticide residues in food or feed.” 40 

2976 CFR 161.202(c)(1); see also 40 CFR 161.202(c)(2) (“results of tests on the 

2977 amount of residues remaining on or in the treated food or feed are needed to 

2978 support a finding as to the magnitude and identity of residue which result in food 

2979 or animal feed as a consequence of a proposed pesticide usage”); 40 CFR 161. 

2980 240(14) (Residue data on indoor use of pesticide “if such a use could result in 

2981 residues in food or feed”). Finally, the revised language also tracks EPA’s 

2982 requirements for residue chemistry data under the current data requirements for 

2983 conventional pesticides in 40 CFR part 158, subpart O. In the preamble to the 

2984 proposed rule, EPA explained that the residue data requirements for 
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2985 antimicrobials were adapted from the conventional data requirements in subpart O 

2986 (73 FR 59401). For uses of conventional pesticides, other than uses in 

2987 agriculture, part 158 states that “[residue chemistry] [d]ata may be required . . . if 

2988 residues may occur in food or feed as a result of the use.” (40 CFR 

2989 158.1410(a)(2)). The regulation also makes clear that this requirement applies 

2990 whether or not a tolerance is needed under FFDCA section 408. The regulation 

2991 specifies that “most products used in or near kitchens require residue data for risk 

2992 assessment purposes even though tolerances may not be necessary in all cases.” 

2993 (Id.) 

2994 The commenters’ concern that the residue chemistry requirements 

2995 exceeded EPA’s jurisdiction under the FFDCA is addressed above in Unit IV. 

2996 B. Complete Transference of the Antimicrobial into Food 

2997 1. Comment. The commenter believes that additional clarification is 

2998 needed concerning EPA’s statement, “in the absence of data [the Agency will] 

2999 evaluate the need for a tolerance or tolerance exemption by assuming complete 

3000 transference of the chemical into food over the lifetime of the treated product.” 

3001 2. EPA’s Response. Complete transference refers to an assumption that 

3002 the Agency would initially make regarding the migration of antimicrobial residues 

3003 from an impregnated food contact material to the food contacting that material 

3004 over the typical use life of the antimicrobial-impregnated material. The worst-case 

3005 assumption is that 100 percent of the antimicrobial residues resulting from use at 

3006 the maximum registered rate transfers into the food, which is then used to 

3007 estimate a conservative dietary exposure. If the aggregate risk calculated using 
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3008 this conservative assumption, from use of the antimicrobial in question, is less 

3009 than EPA’s level of concern, then no measured data are needed. If the aggregate 

3010 risk meets or exceeds EPA’s level of concern, then chemical-specific data 

3011 quantifying residue migration to refine this dietary exposure component may be 

3012 required. To refine the exposure, the applicant may choose to perform one or 

3013 more of the FDA protocols to estimate migration rate into food simulants 

3014 (FDA/CFSAN, 2007, Preparation of Premarket Submissions for Food Contact 

3015 Substances: Chemistry Recommendations (Ref. 11 to the proposed rule, in the 

3016 docket at http://www.regulations.gov)). Alternatively, or subsequently, the 

3017 applicant may choose to conduct a chemical-specific nature of the residue on 

3018 surfaces study and a migration study investigating actual impregnated materials 

3019 using representative foods. 

3020 C. Alternative Formats for Residue Chemistry Data Requirements Table 

3021 Suggested by Commenters 

3022 1. Comment. Two different commenters suggested two different options as 

3023 alternative approaches to the antimicrobial residue chemistry data requirement 

3024 table proposed by EPA. One of the commenters separated the residue chemistry 

3025 data requirements into two tables, referred to as Part 1 and 2 [ACC Comment in 

3026 the docket at http://www.regulations.gov; document EPA-HQ-OPP-2008-0110-

3027 0088.10 p. 7]. The other commenter suggested a single table format [CSPA 

3028 Comment in the docket at http://www.regulations.gov; document EPA-HQ-OPP3029 2008-0110-0086.2]. 

3030 2. EPA’s Response. All three of the commenter-suggested tables had the 

3031 same five “Supporting Information” studies as the table proposed by EPA, but with 
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3032 various mixtures of “R,” “CR,” and “NR.” In the final rule EPA has retained the 

3033 Supporting Information section of the Residue Chemistry Table as proposed. 

3034 EPA has adopted the commenters’ suggestion for a tiered format. After 

3035 review, EPA believes the commenters’ suggested tiered approach is more 

3036 suitable to antimicrobials than that proposed by EPA. All three commenter tables 

3037 suggested that Tier 1 consist of a “Screening-level dietary exposure assessment.” 

3038 Although an applicant may opt to conduct a dietary exposure assessment, EPA 

3039 does not consider this to be a data requirement. Applicants often conduct a 

3040 dietary exposure assessment to understand the dietary risks before submitting an 

3041 application to EPA. If submitted, EPA would review the assumptions used by the 

3042 applicant and compare to EPA’s modeling. If the applicant’s modeling indicates 

3043 that dietary risk is likely to meet or exceed the Agency’s level(s) of concern, the 

3044 applicant may decide to continue on to Tier 2 or 3. Therefore, EPA has not added 

3045 a requirement to conduct a dietary exposure assessment. 

3046 Both the Part 1 Table and the single table suggested that Tier 2 consist of 

3047 a “Refined dietary exposure assessment.” As is the case for the commenter’s 

3048 suggested Tier 1 “Screening-level dietary exposure assessment,” this is optional 

3049 for the applicant; therefore, EPA has not added a requirement to conduct a refined 

3050 dietary exposure assessment. 

3051 Both the Part 1 Table and the single table suggested that Tier 3 consist of 

3052 nature of residue on surface, bioaccumulation, magnitude of residue, residue 

3053 analytical method, and storage stability. These are each addressed individually 

3054 below: 
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3055 i. Nature of residue on surface. The Agency agrees that this study is 

3056 applicable and a valuable addition to the data set necessary to support 

3057 registration and risk assessment of antimicrobial uses on/in food-contact surfaces 

3058 and impregnated materials (treated articles). EPA has added this study into the 

3059 final Residue Chemistry Data Requirements Table in part 158, subpart W. 

3060 ii. Bioaccumulation. EPA believes that the commenters intended that this 

3061 study apply only to fish and that the bioaccumulation study required for ecological 

3062 effects should substitute for the nature of the residue on surface study for aquatic 

3063 uses or indoor/outdoor raw agricultural commodity uses. EPA has found that the 

3064 fish bioaccumulation study is often not useful for residue chemistry purposes 

3065 because characterization of fish residues is only required if the bioconcentration 

3066 (of total residues) factor is > 1000. The fish bioaccumulation study has not been 

3067 adopted by EPA for residue chemistry. Of much more use to residue chemistry 

3068 and retained in this final rule, are the fish metabolism and magnitude of the 

3069 residue studies in fish described in OPPTS Guideline 860.1400. 

3070 iii. Magnitude of residue (MOR). Commenters proposed this study by the 

3071 very general title “Magnitude of residue.” EPA considers MOR to be any study 

3072 designed to quantify “how much” of the residues of concern will result in food, on 

3073 surfaces, in water, etc., following use of an antimicrobial according to label 

3074 directions. The commenters stated in a footnote to this study that, in the case of 

3075 food-contact sanitizers and treated articles, MOR would consist of a migration 

3076 study. Because food-contact sanitizer and treated article uses comprise at least 

3077 80 percent of all antimicrobial food uses, EPA has retained the migration study 
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3078 and the food-handling study by name but has moved them to a different tier. All 

3079 the remaining proposed types of MOR studies are much more rarely required due 

3080 to characteristics such as the use pattern and/or physicochemical properties of 

3081 the antimicrobial in question. For that reason, the following have been grouped as 

3082 “Higher tiered” studies in the final rule: nature of the residue in plants, nature of 

3083 the residue in livestock, residue analytical methods for tolerance enforcement, 

3084 multiresidue method testing, potable water, fish, irrigated crops, 

3085 meat/milk/poultry/eggs, crop field trials, processed food or feed, and anticipated 

3086 residues. 

3087 iv. Residue analytical method. EPA agrees with the commenters that an 

3088 analytical method for data collection is required whenever magnitude of the 

3089 residue studies are required. The Agency has retained this study in the final 

3090 Residue Chemistry Table. 

3091 v. Storage stability. EPA agrees with the commenters that storage stability 

3092 data are required whenever magnitude of the residue studies are required. The 

3093 Agency has retained this study in the final Residue Chemistry Table. 

3094 The Part 2 Table did not recommend requiring a Refined Dietary Exposure 

3095 Assessment. Rather, its Tier 2 consists of studies entitled nature of the residue in 

3096 commodity, nature of the residue in livestock, residue analytical methods for 

3097 enforcement of tolerances, multiresidue analytical method, magnitude of the 

3098 residue: in commodities, in water, and in meat/milk/poultry/eggs, storage stability, 

3099 and anticipated residues. EPA agrees that all of these studies should be required 

3100 and has retained all of them in the highest tier in the final Residue Chemistry 
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3101 Table. Note that two of the commenter-suggested studies (nature of the residue 

3102 in commodity and magnitude of the residue in commodities) were considered 

3103 applicable only to RACs treated via a fruit and vegetable rinse; whereas, the 

3104 analogous EPA data requirements apply to both crop plants and metabolically3105 active RACs. The data requirements in EPA’s final rule easily subsume the 

3106 studies suggested by a commenter in Part 2. The commenters feel that EPA only 

3107 has authority to require residue data for RACs of plants treated by a fruit or 

3108 vegetable rinse whereas EPA interprets FIFRA and FFDCA, as amended by 

3109 FQPA, to mean that data may be required for any use if necessary to support 

3110 registration of any use under FIFRA (see Units XVI.A and IV). 

3111 As evidenced by the recommendation to divide EPA’s single proposed data 

3112 requirement table into two tables (Parts 1 and 2), the commenters believe the 

3113 data requirements are distinctly different depending on the use pattern of interest. 

3114 While this is sometimes the case, the Agency has found that there is much 

3115 overlap between which studies are necessary to characterize the dietary exposure 

3116 potentially resulting from a given use. This is why the test notes provide the 

3117 conditions under which each study is required, likely to be required, or not 

3118 required. EPA has historically and currently used a single data requirement table 

3119 for each scientific discipline; doing so permits the interrelationships between use 

3120 pattern, tiering, and data needs to be fully evident. 

3121 The commenters did not account for data needed to estimate dietary 

3122 exposure associated with uses that do not require a FFDCA section 408 tolerance 

3123 or exemption (see Unit XVI.A and Unit IV). The commenters also did not account 
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3124 for data needed to estimate dietary exposure from food residues inadvertently 

3125 resulting from, but not limited to, discharges of antimicrobial-treated water from 

3126 indoor industries, leaching from preserved lumber, or treatment of food crops 

3127 when a public health claim is made on the label. 

3128 XVII. Discussion of Key Comments on SAR and QSAR, and the OPPTS (now 

3129 OCSPP) Integrated Testing Vision

3130 A. Guidance on Policies, Procedures, and Processes

3131 1. Comment. A commenter asked EPA to should provide clear guidance 

3132 on its policies, procedures, and processes on the use of alternative technologies 

3133 such as SAR and QSAR, and the WOE approach. In addition, the commenter 

3134 stated that EPA should also provide education and training on these approaches. 

3135 2. EPA’s Response. The Agency encourages applicants to create 

3136 submissions that include predictive techniques such as SAR and QSAR to fulfill 

3137 data requirements. As described in the white paper to the proposed rule, entitled, 

3138 “Use of Structure-Activity Relationship (SAR) Information and Quantitative SAR 

3139 (QSAR) Modeling For Fulfilling Data Requirements for Antimicrobial Pesticide 

3140 Chemicals and Informing EPA’s Risk Management Process” (document 45 in the 

3141 docket at http://www.regulations.gov), an important part of the applicant’s 

3142 submission is the rationale. The rationale, or WOE evaluation, is the part of the 

3143 submission that explains the applicant’s belief as to why and how the predictive 

3144 data would fulfill the data requirement. The WOE approach requires a critical 

3145 analysis of the entire body of available data for consistency and biological 

3146 plausibility. In support of a request that predictive data be considered, the 

3147 applicant would need to explain why it believes the surrogate data or the modeling 
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3148 are appropriate for the intended use and are of sufficient completeness and 

3149 quality, and therefore would fulfill the data requirement. The Agency would 

3150 evaluate each submission with a WOE rationale on a case-by-case basis. 

3151 The general types of information that are considered appropriate for a 

3152 WOE approach would include: 

3153 • Sufficiency of data. Studies that completely characterize both the effects 

3154 and exposure of the agent have more credibility and support than studies that 

3155 contain data gaps. 

3156 • Quality of the data. Potentially relevant studies are judged for quality and 

3157 studies of high quality are given more weight than those of lower quality. 

3158 • Evidence of causality. The degree of correlation between the presence of 

3159 an agent and some adverse effect is an important consideration. 

3160 Regarding SAR/QSAR, the white paper to the proposed rule (p. 30) 

3161 discusses the five criteria set by the OECD for evaluating a model. EPA 

3162 encourages submitters to follow the established criteria set by OECD, and show 

3163 how the model is validated for that particular pesticide chemical structure as a 

3164 measure of the model’s applicability. 

3165 Different computer software programs are used to estimate/predict different 

3166 hazards (see: http://www.epa.gov/oppt/sf/tools/methods.htm). This means that 

3167 predictive software models for different scientific disciplines are not at the same 

3168 level of development. The Agency has long standing experience in predicting 

3169 (modeling) physical-chemical properties, environmental fate, ecotoxicity, and 

3170 experience in predicting carcinogenesis for certain classes of chemicals. 
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3171 However, the Agency is still gaining experience to become familiar with predictive 

3172 approaches that look at other human health endpoints (e.g., reproductive, 

3173 developmental), which have not been widely used at EPA. Given the different 

3174 stages of predictive software development, EPA would expect to undertake a 

3175 case-by-case evaluation of submitted WOEs. EPA encourages the use of 

3176 integrated approaches that combine the knowledge from existing databases about 

3177 the chemical of interest with data from appropriate surrogate chemicals. 

3178 EPA agrees that guidance on the policies, procedures, and processes for 

3179 using alternative approaches such as SAR/QSAR is needed. EPA is developing 

3180 such a guidance document for pesticides and is seeking to harmonize its 

3181 approach with that of Canada’s Pest Management Regulatory Authority. It is 

3182 anticipated that the guidance document would be issued as a North American 

3183 Free Trade Agreement guidance document by the end of 2011. This guidance 

3184 document will adhere to the five OECD principles that were discussed in the white 

3185 paper. Once finalized, this document will be the definitive source of information 

3186 for applicants seeking to use SAR and QSAR approaches for fulfilling data 

3187 requirements for pesticide registration. 

3188 B. Integrating SAR/QSAR within the Data Requirements Rule

3189 1. Comments. One commenter argued that there should be an explicit 

3190 statement that SAR and QSAR can be considered to fulfill data requirements. 

3191 Another commenter had concerns on codifying the use of SAR in 40 CFR part 

3192 158, Subpart A since that would mean that “SAR/QSAR Techniques would be 

3193 applicable to conventional, biochemical and microbial, and antimicrobials 
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3194 pesticide chemicals.” Another commenter requested that SAR/QSAR be fully 

3195 integrated within the rule. 

3196 2. EPA’s Response. EPA has and will continue to consider accepting 

3197 SAR/QSAR to fulfill its data requirements on a case-by-case basis. Acceptance 

3198 would be based on the information provided and most especially on the 

3199 supporting rationale submitted to EPA. The Agency would evaluate the 

3200 information submitted to determine if the applicant has provided information that is 

3201 of sufficient quality and completeness. The Agency notes that validation of QSAR 

3202 models is necessary before the predictions from those models can be fully 

3203 integrated into the testing requirements. To that end, QSAR models must be 

3204 inclusive of pesticide toxicology data and chemical structures. Until these models 

3205 become customized with pesticide information, full incorporation of predictive tools 

3206 likely will be limited to a case-by-case basis. 

3207 EPA agrees that if use of SAR/QSAR were to be codified in subpart A, that 

3208 it would be applicable to all pesticide chemicals. At this time, EPA is not codifying 

3209 the use of SAR and QSAR in subpart A. 

3210 XVIII. Discussion of Key Comments on Guidelines 

3211 A. Commenters’ Concerns with Guidelines

3212 1. Comment: Several commenters indicated their belief that the current 

3213 Harmonized Guidelines have significant problems, which include: 

3214  Lack of guidelines could create an unevenness from one company to 

3215 another in how the data requirements are applied. 

3216  Data requirements for which guidelines are not available. 
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3217  Older, outdated guidelines that need revision. 

3218  Draft guidelines that need to be finalized. 

3219  Older exposure guidelines that do not include information about the 

3220 Human Studies Review Board. 

3221  Guidelines that were adopted without the opportunity for public 

3222 comment. 

3223 According to the commenters, lack of current guidelines could create an 

3224 unevenness from one company to another in how the data requirements are 

3225 applied. The commenter argued that the Agency needs to provide current, 

3226 consistent, and reliable guidance and standards for each data requirement. The 

3227 commenters recommended that EPA should finalize all of its guidelines before the 

3228 final rule is published per the recommendation from OMB. 

3229 2. EPA’s Response. EPA’s Harmonized Test Guidelines are publicly3230 available at http://www.epa.gov/ocspp/pubs/frs/home/guidelin.htm. The 

3231 Harmonized Guidelines contain recommendations on how to conduct a study that 

3232 is most likely to provide the information needed by EPA for making a registration 

3233 decision. . 

3234 The Harmonized Guidelines are guidance. The guidelines themselves do 

3235 not impose mandatory requirements. Applicants are not required to submit studies 

3236 developed according to the guidelines to fulfill a data requirement. However, EPA 

3237 encourages applicants to use the guidelines. These guidelines were developed to 

3238 provide applicants, who would be conducting the studies, with recognized 

3239 approaches for developing high quality data, guidance on evaluating and reporting 
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3240 data, definition of terms, and suggested study protocols. It would not be possible 

3241 to address every conceivable circumstance that could occur when conducting a 

3242 particular study. Instead the guidelines provide a framework that provides 

3243 recommended approaches for conducting studies while offering flexibility and 

3244 accommodation for individual circumstances where appropriate. EPA has 

3245 reviewed and accepted many studies, on a case-by-case basis, that were not 

3246 conducted in accordance with current guidelines, but which provided suitable 

3247 information for risk assessment purposes. 

3248 Since guidelines cannot account for every conceivable circumstance, EPA, 

3249 for certain studies, proposed a “required” or “highly suggested” protocol 

3250 submission and review step in the test notes to the tables in the proposed rule. 

3251 Generally, these pertain to those studies that are “newer” or have not been 

3252 routinely conducted. Given that the applicant community and contracting 

3253 laboratories would have less experience in conducting these kinds of “newer” 

3254 studies, protocol submission, review, and meetings about proposed protocols are 

3255 beneficial to both the applicant and EPA, and help assure that the study submitted 

3256 for review should provide the information needed by EPA for its registration 

3257 decision. 

3258 EPA acknowledges that in some instances there are: Data requirements 

3259 for which guidelines are not available; outdated guidelines that need revision; and 

3260 draft guidelines that need to be finalized. Ideally, up-to-date final guidelines would 

3261 be available for every data requirement. Up-to-date guidelines increase the 

3262 possibility that EPA will receive useful data and that applicants can produce such 
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3263 data in the most cost-efficient and consistent manner. However, given the rapidly 

3264 evolving scientific methods for conducting toxicity, exposure, and ecological 

3265 studies with pesticides, study guidelines often need frequent updating to include 

3266 the latest techniques and methods. Moreover, the need for openness and 

3267 transparency means that developing a guideline or updating an existing one can 

3268 be a lengthy process. In a recent letter to CropLife America (June 26, 2009), 

3269 (Ref. 11) the Agency discussed the timeframe for developing the Terrestrial Field 

3270 Dissipation Guideline (835.6100), which spanned 15 years. During that time 

3271 period, there were presentations to the SAP, at various symposia including ones 

3272 conducted by the American Chemical Society and the American Society of 

3273 Agronomy, and to a workshop in Washington, DC co-hosted by EPA and 

3274 Canada’s Pest Management Regulatory Agency. 

3275 Thus, the reality is that test guidelines will always be a work in progress. At 

3276 the same time, EPA is implementing a regulatory program under FIFRA and 

3277 FFDCA section 408 under which it must make timely decisions on the safety of 

3278 pesticide products based on toxicity and exposure testing. Guidance on optimal 

3279 testing procedures remains an Agency goal but the absence of testing guidelines 

3280 is not a barrier to the imposition of testing requirements necessary to make the 

3281 required statutory findings. 

3282 In 2008, OMB, during its Executive Order 12866 review of the proposed 

3283 rule, recommended that certain draft guidelines be finalized before publishing the 

3284 Antimicrobial Data Requirements final rule. These guidelines were: 

3285  Applicator product use information (OPPTS 875.1700) 
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3286  Post application product use information (OPPTS 875.2700). 

3287  Indoor surface residue dissipation (OPPTS 875.2300). 

3288  Non-dietary ingestion (OPPTS 875.3000). 

3289 In the proposed rule (October 8, 2008; 73 FR 59382), EPA discussed that 

3290 the publicly-available versions of these guidelines were only available on the SAP 

3291 portion of EPA’s website (73 FR 59399 – 59401). EPA intends to finalize these 

3292 guidelines in the near future. Also, as previously discussed, the data requirement 

3293 referencing the non-dietary ingestion guideline was removed from the final Post3294 Applicator Exposure Table in § 158.2270. (see Unit XIII.D). 

3295 EPA acknowledges that the guidelines for dermal and inhalation exposure 

3296 studies need revisions to account for new advances in how exposure is measured 

3297 and modeled. To provide needed information to the public and applicants, EPA 

3298 will change the way these guidelines are referenced on the Harmonized 

3299 Guidelines website by adding links to the SAP and Human Studies Review Board 

3300 (HSRB) meetings at which the changes needed to conduct one of these studies 

3301 were publicly discussed. 

3302 Since the publication of the proposed rule on October 8, 2008, EPA has 

3303 worked to update and finalize a number of guidelines. On April 15, 2009, EPA 

3304 published in the Federal Register (74 FR 17479) a Notice of Availability 

3305 describing updates to 16 environmental fate guidelines. On January 27, 2010, (75 

3306 FR 4380) EPA published four draft product performance guidelines for comment. 

3307 These four guidelines (810.2000, 810.2100, 810.2200, and 810.2300) were 

3308 developed over an extended period of time with multiple levels of review across 
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3309 divisions and program offices in EPA, expert external peer review by the FIFRA 

3310 Scientific Advisory Panel, and discussions with and comments from the regulated 

3311 community. Many of the technical changes described in these four draft 

3312 guidelines have been in use by the Agency for several years. Three additional 

3313 product performance guidelines (810.2400, 810.2500, and 810.2600) should be 

3314 published for comment in a timeframe similar to that of publication of the final rule 

3315 for Antimicrobial Data Requirements. Similarly, the nontarget organism and plant 

3316 protection guidelines are expected to be finalized by the end of 2011. 

3317 Before finalizing a guideline, EPA provides many opportunities for public 

3318 comment. EPA’s commitment to transparency is not new. Transparency allows 

3319 all stakeholders to know what, how, and why EPA is adopting a guideline. EPA’s 

3320 procedures for developing a guideline is described in a Notice of Availability that 

3321 published on August 28, 1996 (61 FR 44308): 

3322  Guidelines under development (whether new or being substantially 

3323 revised) are made available for public comment. 

3324  Guidelines under development (whether new or being substantially 

3325 revised) undergo an external peer review process. Most commonly, the peer 

3326 review process would be a review by the FIFRA SAP. 

3327  Reformatted guidelines (no substantial revisions) are not subject to 

3328 review and comment. 

3329  Public review and comment is also used when EPA guidelines are 

3330 being harmonized with OECD guidelines. 

3331 B. Harmonization of Guidelines with OECD
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3332 1. Comment. EPA should harmonize its guidelines with those of OECD. 

3333 2. EPA’s Response. EPA agrees with this comment and is continuing to 

3334 harmonize guidelines, to the extent practicable, as they are revised. As noted on 

3335 its website http://www.epa.gov/pesticides/science/guidelines.htm, EPA has 

3336 several harmonization activities underway with the OECD. The Master List of 

3337 Harmonized Test Guidelines includes a reference to an OECD guideline, once 

3338 harmonized. All harmonized OECD test guidelines 

3339 (http://www.epa.gov/epahome/exitepa.htm) fall under the OECD Mutual 

3340 Acceptance of Data decision, which calls for acceptance for regulatory use by all 

3341 OECD member nations. Additionally, under 40 CFR 158.70(d)(2), acceptance of 

3342 testing conducted in accordance with OECD protocols is described. 

3343 Harmonized test guidelines reduce the burden on chemical producers and 

3344 conserve scientific resources, including the minimal use of laboratory test animals. 

3345 They also form a basis for work sharing and cooperation among all OECD 

3346 countries. U.S. experts are engaged in harmonization activities through OECD to 

3347 revise toxicology and ecotoxicology test guidelines. These revisions will 

3348 emphasize reduction, refinement, or replacement of animal testing, while 

3349 incorporating the latest advances in science. Animal welfare concerns and 

3350 international regulatory needs are being considered in the course of these 

3351 revisions of the test guidelines. In addition, EPA is actively engaged in OECD’s 

3352 development and harmonization efforts for guidelines to address environmental 

3353 fate, endocrine disruptor screening, and efficacy of antimicrobial pesticides. 
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3354 Tests conducted in accordance with the requirements and 

3355 recommendations of the applicable OECD protocols can be used to develop data 

3356 necessary to fulfill the data requirements. However, some of the OECD 

3357 recommended test standards, such as test duration and selection of test species, 

3358 are less restrictive than those recommended by EPA. When using OECD 

3359 protocols, applicants should be careful to observe the test standards so that the 

3360 data generated will satisfy the EPA data requirements. 

3361 C. Guidelines Specific to Antimicrobials 

3362 1. Comment. The commenter claimed that guidelines specific to 

3363 antimicrobials are needed. 

3364 2. EPA’s Response. EPA agrees that for certain scientific disciplines or 

3365 certain studies that antimicrobial-specific guidance may be needed. The data 

3366 required to demonstrate product performance would be very different for an insect 

3367 repellent or a termiticide versus that needed for sanitizers and disinfectants. 

3368 Exposure studies could be conducted differently for an antimicrobial used in a 

3369 food-processing plant versus a conventional pesticide sprayed on an agricultural 

3370 field. Exposure studies could also be conducted via the same method: A spray 

3371 can with an insecticide is assessed using the same techniques as a spray can 

3372 with a disinfectant with any differences in the assessment being attributed to 

3373 actual use conditions, such as, indoors versus outdoors or surfaces sprayed. For 

3374 other scientific disciplines such as toxicology or product chemistry, generally, with 

3375 a few exceptions, the guidance would be the same: A carcinogenicity, 

3376 developmental, or reproductive toxicity study would be conducted similarly for an 
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3377 antimicrobial or a conventional pesticide. However, as noted in Unit X.F, the 

3378 Ames assay may not be useful for assessment of mutagenic potential of 

3379 antimicrobial pesticides. 

3380 XIX. Discussion of Key Comments on Endangered Species Assessments 

3381 A. Endangered Species Assessment for Antimicrobials 

3382 1. Comment. The commenter argued that EPA needs to recognize the 

3383 manner in which antimicrobials may result in environmental exposure and the 

3384 regulations under statutes other than FIFRA in order to promote an effective and 

3385 efficient approach to regulating antimicrobial pesticides with regard to endangered 

3386 and threatened species. According to the commenter, antimicrobials are not 

3387 applied directly to the environment, but environmental exposures from 

3388 antimicrobial pesticides result from point-source discharges or slow release from 

3389 pesticide-containing materials. 

3390 2. EPA’s Response. EPA agrees that there are differences between 

3391 antimicrobial pesticides and agricultural pesticides. As discussed in the proposed 

3392 rule (October 8, 2008; 73 FR 59425), for agricultural pesticides, there is generally 

3393 greater specificity relative to where a pesticide may be used compared to 

3394 antimicrobial pesticides. Agricultural pesticides are typically used on crops. As 

3395 part of its endangered and threatened species assessment, EPA extracts 

3396 information on county-level crop occurrence and acreage within counties of particular 

3397 crops from the most recent U.S. Department of Agriculture’s National Agricultural 

3398 Statistics Services’ Census of Agriculture. Because antimicrobial pesticides are 

3399 typically not applied directly to the environment, it is easier to delineate and overlay 

3400 agricultural pesticide use with endangered or threatened species locations than to 
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3401 delineate and overlay antimicrobial pesticides use. Nevertheless, wood 

3402 preservatives, antifoulant paints and coatings, and other antimicrobial uses, 

3403 including uses in swimming pool water, industrial slimicides used in recirculating 

3404 water cooling towers, and paper mills, have the potential for environmental 

3405 exposures. The Agency is working to refine its endangered species assessment 

3406 for antimicrobial pesticides to account for the unique mechanisms involved in 

3407 application and use of antimicrobial pesticides, and the different routes through 

3408 which antimicrobial pesticides enter the environment. 

3409 EPA recognizes that antimicrobials, like any other pesticide product, may 

3410 be subject to other Federal, State and local laws. FIFRA requires that, before a 

3411 pesticide may be lawfully sold or distributed in the United States, the product must 

3412 be registered by EPA, unless the product is exempt from registration 

3413 requirements. Prior to registering a pesticide product, EPA must first ensure that 

3414 the pesticide, when used according to label directions, can be used without posing 

3415 unreasonable risks to humans and the environment. The registration of a 

3416 pesticide product, whether it is an antimicrobial or other type of pesticide product, 

3417 is considered an “action” subject to the Endangered Species Act (ESA). The ESA 

3418 requires all Federal agencies to ensure that any action they permit or authorize 

3419 will not result in likely jeopardy to the continued existence of endangered or 

3420 threatened species, or destroy or adversely modify habitat designated as critical 

3421 by the U.S. Fish and Wildlife Service (FWS) or National Marine Fisheries Service 

3422 (NMFS). 
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3423 In order to ensure EPA’s actions are consistent with the ESA, the Agency 

3424 must assess the potential for both direct and indirect effects to any potentially 

3425 exposed threatened or endangered species and critical habitat, independent of 

3426 whether exposure results from a point-source discharge or the slow release of a 

3427 pesticide containing material. If effects may occur, EPA consults with the FWS or 

3428 NMFS to determine whether there may be jeopardy to the species or destruction 

3429 or adverse modification to habitat designated as critical. 

3430 B. Method for Conducting Endangered Species Assessments 

3431 1. Comment. A commenter claimed that EPA/OPP does not have a 

3432 mature program currently in place for antimicrobial environmental risk assessment 

3433 generally. More specifically, the commenter contended that EPA does not have a 

3434 program in place for assessing potential impacts on endangered and threatened 

3435 species relevant to antimicrobials and their uses. The commenter argued that until 

3436 EPA scientifically substantiates data requirements to use in estimating 

3437 antimicrobial environmental exposures and modeling the potential for risks from 

3438 such exposures, it will not be feasible to make any meaningful determinations on 

3439 potential impacts to endangered species. The commenter concluded that it is 

3440 thus premature for the EPA to determine how it should approach antimicrobials 

3441 with regard to endangered species. 

3442 2. EPA’s Response. EPA disagrees with the commenter. EPA has a 

3443 robust program for completing antimicrobial environmental risk assessments, as 

3444 outlined in the preamble to the proposed rule (73 FR 59405). Environmental fate 

3445 studies evaluate the mobility, distribution and dissipation of a pesticide in various 
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3446 compartments of the environment, such as water, soil, air, and sediment. 

3447 Ecological effects data are used by the Agency to determine the toxicological 

3448 hazards of pesticides to various nontarget organisms, such as birds, mammals, 

3449 fish, bees, terrestrial and aquatic invertebrates, and plants. The required 

3450 environmental fate studies and ecological effects (both plant and animal) data 

3451 provide the foundation for an environmental risk assessment. EPA’s 

3452 environmental risk assessment for antimicrobials combines environmental fate 

3453 studies with ecological effects data to determine the potential of the pesticide to 

3454 cause harmful effects to nontarget organisms and plants. The data requirements 

3455 that will be codified in the final rule will provide sufficient information for EPA to 

3456 perform an ecological risk assessment. 

3457 EPA/OPP’s process for assessing the potential risks of a pesticide to 

3458 federally listed threatened or endangered species and their designated critical 

3459 habitat is described in the document titled “Overview of the Ecological Risk 

3460 Assessment Process in the Office of Pesticide Programs, U.S. Environmental 

3461 Protection Agency – Endangered and Threatened Species Effects 

3462 Determinations” released in January 2004. Appendix A to that document – 

3463 “Overview of OPP’s Screening-Level Ecological Risk Assessment Process for 

3464 Antimicrobial Pesticides” – explains both the data needed and the process that 

3465 would be used by EPA to assess potential risks to endangered and threatened 

3466 species from antimicrobial pesticides. 

3467 EPA’s assessment of potential impacts on endangered and threatened 

3468 species begins with a screening level assessment to determine if there is a 
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3469 potential concern. When the screening-level ecological risk assessment raises 

3470 potential concerns related to a listed species, EPA then conducts a species-specific 

3471 evaluation to refine the assessment. The more refined assessment should involve 

3472 clear delineation of the action area associated with the proposed use of the 

3473 pesticide and best available information on the temporal and spatial co-location of 

3474 the listed species with respect to the action area. EPA notes that with the 

3475 publication of the proposed rule, the discussion in Appendix A is out of date. In 

3476 response to comments received on the proposed antimicrobial data requirements, 

3477 EPA indicated it is no longer relying on its proposed approach classifying use 

3478 patterns as high/low or minimal/significant exposure uses with regard to ecological 

3479 effects testing. However, the Agency’s basic approach to endangered species 

3480 risk assessments, which combine environmental fate studies with ecological 

3481 effects data to determine the potential of the pesticide to cause harmful effects to 

3482 endangered species, has not changed. In addition, the Agency will conduct an 

3483 assessment for antimicrobial pesticides with down-the-drain uses, as described in 

3484 response to comment 134.1 in the Response to Comments Document in the 

3485 docket at http://www.regulations.gov. The codified data requirements and the 

3486 down-the-drain assessment will extend AD’s ability to understand the potential 

3487 impacts of antimicrobial pesticides on endangered species.

3488 EPA cannot wait to comply with the ESA until newer, more advanced, 

3489 models are available or additional data needs are determined: Federal agencies 

3490 must comply with the ESA by performing their assessments and analyses using 

3491 the best scientific and commercial data available. As a part of Registration 

3492 Review, EPA is conducting species-specific environmental risk assessments that 
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3493 will allow EPA to determine whether the antimicrobial pesticide product has “no 

3494 effect” or “may affect” federally-listed threatened or endangered species (listed 

3495 species) or their designated critical habitats. When an assessment concludes that 

3496 a pesticide product’s use “may effect” a listed species or its designated critical 

3497 habitat, the Agency will consult with the FWS and/or NMFS, as appropriate. 

3498 XX. Discussion of Key Comments on Endocrine Disruption 

3499 A. Comment 

3500 The commenters noted that EPA did not include any studies to assess 

3501 endocrine disruption effects. 

3502 B. EPA’s Response 

3503 The commenter is correct that EPA did not include within the proposed 

3504 subpart W, studies whose sole purpose is to assess endocrine disruption effects 

3505 in avian and aquatic species. The Agency is also not including such studies in this 

3506 final rule. 

3507 With regards to toxicology data requirements, as required by FIFRA and 

3508 FFDCA, EPA reviews a toxicological database of numerous studies to assess 

3509 potential adverse outcomes from exposure to chemicals. Collectively, these 

3510 studies include acute, subchronic and chronic toxicity, including assessments of 

3511 carcinogenicity, neurotoxicity, developmental, reproductive, and general or 

3512 systemic toxicity. These studies include endpoints which may be susceptible to 

3513 endocrine influence, including effects on endocrine target organ histopathology, 

3514 organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, 

3515 reproductive loss, and sex ratios in offspring. EPA reviews these data and selects 
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3516 the most sensitive endpoints for relevant risk assessment scenarios from the 

3517 existing toxicological database. 

3518 With regards to ecotoxicity data requirements, as required by FIFRA and 

3519 FFDCA, EPA reviews a nontarget organism database of numerous studies to 

3520 assess potential adverse outcomes from exposure to chemicals. For ecological 

3521 hazard assessments, EPA evaluates acute tests and chronic studies that assess 

3522 growth, developmental and reproductive effects in different taxonomic groups. 

3523 EPA reviews these data and selects the most sensitive endpoints for relevant risk 

3524 assessment scenarios from the existing nontarget organism database. 

3525 Through a separate effort, the Agency has also developed a screening 

3526 battery to identify chemicals that may have effects on the hormone systems of 

3527 humans and wildlife. As required under FFDCA section 408(p), the Agency 

3528 developed the Endocrine Disruptor Screening Program (EDSP) to determine 

3529 whether certain substances (including pesticide active and other ingredients) may 

3530 have an effect in humans or wildlife similar to an effect produced by a “naturally 

3531 occurring estrogen, or other such endocrine effects as the Administrator may 

3532 designate.” The EDSP employs a two-tiered approach to making the statutorily 

3533 required determinations. Tier 1 consists of a battery of 11 screening assays to 

3534 identify the potential of a chemical substance to interact with the estrogen, 

3535 androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through 

3536 Tier 1 screening and are found to have the potential to interact with E, A, or T 

3537 hormonal systems will proceed to the next stage of the EDSP where EPA will 

3538 determine which, if any, of the Tier 2 tests are necessary based on the available 
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3539 data. Tier 2 testing is designed to identify any adverse endocrine-related effects 

3540 caused by the substance, and establish a dose-response relationship between the 

3541 dose and the E, A, or T effect. 

3542 Between October 2009 and February 2010, EPA issued test orders/data 

3543 call-ins for 58 pesticide active ingredients and nine inert ingredients. This list of 

3544 chemicals was selected based on the potential for human exposure through 

3545 pathways such as food and water, residential activity, and certain post-application 

3546 agricultural scenarios. This list should not be construed as a list of known or likely 

3547 endocrine disruptors. 

3548 Under FFDCA section 408(p) the Agency must screen all pesticide 

3549 chemicals, including antimicrobials. Accordingly, EPA anticipates issuing future 

3550 EDSP test orders/data call-ins for all pesticide active ingredients. 

3551 For further information on the EDSP including the status and test 

3552 guidelines, please visit the website: http://www.epa.gov/endo/. 

3553 XXI. Discussion of Key Comments on Effective Date 

3554 A. Comment 

3555 Several commenters have expressed concern over when the final rule 

3556 would take effect. One commenter stated that compliance with the Administrative 

3557 Procedures Act requires EPA to apply any final rulemaking on data requirements 

3558 for antimicrobials only to applications submitted after the effective date; otherwise, 

3559 EPA would be promulgating the final rule retroactively. The commenter also 

3560 asserted that EPA should be consistent in its implementation of effective dates, 

3561 noting that EPA did not impose new data requirements on pending conventional 
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3562 pesticide registrants when the conventional pesticide rules were revised. A 

3563 second commenter suggested that registrations pending at the time of the final 

3564 rule publication be given conditional registration under section 3(c)(7) of FIFRA or 

3565 under 3(c)(5) if the requirements of part 161 have been met, and that 

3566 implementation of the part 158, subpart W data requirements occur at the time of 

3567 periodic registration review. Another commenter noted that EPA has provided 

3568 reasonable notice to registrants and recommends that EPA implement the rule as 

3569 soon as technically feasible. A different commenter questioned whether 

3570 additional Pesticide Registration Improvement Act (PRIA) registration fees would 

3571 be required for pending applications if the registrant did not meet new data 

3572 requirements and withdrew the application, or if the Agency issued a 

3573 determination that it cannot grant the application. 

3574 B. EPA’s Response

3575 EPA will follow an approach similar to that used for conventional pesticides 

3576 following the promulgation of that portion of 40 CFR part 158. 

3577 As previously discussed, the final rule for antimicrobials contains 11 “new” 

3578 data requirements. “New” means that the data requirement has never been 

3579 required, or has rarely been required on a case-by-case basis and has not been 

3580 routinely considered during the Agency’s evaluation of the data needed for the 

3581 purpose of risk assessment. The new data requirements being codified include 

3582 eight that were proposed and three that have been added based on public 

3583 comments received about the proposed rule. 
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3584 EPA recognizes that during early implementation of 40 CFR part 158, 

3585 subpart W not all application packages may have all of the newly-required data. 

3586 Therefore during early implementation of 40 CFR part 158, subpart W, EPA will 

3587 accept for review and evaluation application packages that may not have all of the 

3588 newly required data in appropriate cases supported by adequate justification. 

3589 This early implementation period could extend up to two years post-promulgation 

3590 for situations in which a more time-intensive new study is missing but could be 

3591 less for other situations, such as for less time-intensive new studies. The 

3592 applicant should address the issue of timing (i.e., why the data are not yet 

3593 submitted and when the data can be submitted) with respect to any missing 

3594 newly-required data, in their justification. 

3595 EPA is statutorily required to evaluate the proposed pesticide thoroughly to 

3596 ensure that it will not unreasonably harm human health or the environment. For 

3597 pesticides needing FFDCA section 408 tolerances, EPA is statutorily required to 

3598 make a safety finding that the pesticide can be used with "reasonable certainty of 

3599 no harm." In cases where the application may not have all the required data, EPA 

3600 would evaluate whether a registration determination or a safety finding can be 

3601 made based on the available data or on the results of other studies in the 

3602 pesticide’s database. If there is insufficient information, and if the database does 

3603 not provide information on the endpoints that would be tested, or data provided by 

3604 the applicant or information in the database shows evidence of effects, EPA may 

3605 not be able to make a registration decision or safety finding. In such cases, the 

3606 application may be denied or the applicant may choose to withdraw the 
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3607 application pending completion of the needed data. In some cases, conditional 

3608 registrations may be appropriate for consideration. Among other things, a 

3609 determination that the proposed use will not significantly increase the risk of 

3610 unreasonable adverse effects on the environment will need to be made. If EPA 

3611 can make that determination and the other elements for a conditional registration 

3612 are met, then a conditional registration may be appropriate and the new data 

3613 required as a condition of registration. If there is a basis for granting a conditional 

3614 registration, then the timeframe for conditioning the registration would be 

3615 determined based on factors such as the required studies involved and the length 

3616 of time required to conduct those studies. 

3617 Importantly, it should be noted that acceptance of an application for 

3618 processing during early implementation of 40 CFR part 158, subpart W that does 

3619 not result in a conditional registration does not permanently relieve the applicant 

3620 from providing the newly required data. Based on the particular case involved, 

3621 the Agency will employ appropriate mechanisms, for example, through a DCI or 

3622 through the registration review process, to ensure the generation and submission 

3623 of any missing newly-required data. 

3624 With respect to pending applications that are withdrawn, additional PRIA 

3625 registration fees will generally only be required if the applicant seeks to pursue the 

3626 action again by submitting a new application (and addressing the deficiencies in 

3627 the original application). In withdrawal situations, the Agency provides a refund for 

3628 any work that the Agency did not perform on the application following a 

3629 withdrawal. Similarly, a determination that the application cannot be granted does 
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3630 not require additional PRIA registration fees. In that case, additional fees will only 

3631 be incurred if the application is subsequently withdrawn or denied, and the 

3632 applicant seeks to pursue the action again and submits a new application. 

3633 XXII. Discussion of Key Comments on the Economic Analysis

3634 A. Comparing Estimates of Cost of the Proposed Rule

3635 

3636 1. Comment. A commenter performed an independent economic analysis 

3637 (EA) for the proposed rule. According to the commenter’s analysis, the cost of 

3638 proposed part 158, subpart W is greater than that estimated by the EPA. In 

3639 addition, the unit test costs and frequency of tests used in the commenter’s 

3640 analysis are different than EPA’s. 

3641 2. EPA’s Response. EPA reviewed the commenter’s analysis and based 

3642 on that review revised the EA for the final rule. EPA’s evaluation of the 

3643 commenter’s EA indicated there were the following differences between the two 

3644 EAs: 

3645  The cost estimates used for the studies 

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

3647  Costs for Registration Review (see Unit XXII.C.) 

3648 The differences between the cost of the proposed rule as estimated by the 

3649 commenter and the cost as assessed by the Agency for new registrations are 

3650 explained in the following subunits. 

3651 i. How data requirement costs are calculated. The annual cost of a data 

3652 requirement is the product of three factors: unit test cost, probability of the test 

3653 being required, and the number of registrations in the industry per year for the 

3654 registration type and use. That is: 
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3655 Industry Cost of a data requirement = Unit test cost x test probability x number of 

3656 registrations 

3657 These costs are summed for all data requirements, uses, and registration types to 

3658 get the total annual cost of the data requirements for the industry. 

3659 ii. Differences in unit test costs. EPA acknowledges that there are 

3660 significant differences between the Agency’s analysis and the commenter’s 

3661 analysis regarding the unit test costs. According to the commenter’s EA, the costs 

3662 were provided to them by their client’s technical consultants, and are “based on 

3663 quotes from laboratories, actual experience, and professional judgment.” The 

3664 commenter did not provide sufficient information with which to evaluate the 

3665 commenter’s test cost estimates. Additionally, EPA notes that having all test cost 

3666 estimates ending in zero could be indicative of estimation. 

3667 EPA’s unit test costs for each data requirement were obtained by 

3668 contacting established contract research organizations (CROs) to assess what the 

3669 labs would charge to conduct studies according to specific designs provided by 

3670 EPA, or as specified in OPPTS guidelines. Upper and lower cost estimates were 

3671 requested. For each test, the upper cost estimates from each CRO were 

3672 averaged to obtain a high average estimate. A similar calculation was done for 

3673 the lower cost estimate. EPA’s estimate is the average of the high and low 

3674 average estimates. 

3675 iii. Test costs and overhead costs. The commenter added 30 percent to 

3676 their test cost estimates to account for the overhead of the registrants managing 

3677 and overseeing the tests they contract to the labs. EPA acknowledges that there 
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3678 are costs other than test costs associated with registering and maintaining the 

3679 registrations of pesticide products. Overhead is a not new cost, attributable to the 

3680 rule, and EPA does not believe that overhead costs will change significantly as a 

3681 result of codifying data requirements for antimicrobials. EPA does not include 

3682 overhead costs in its economic analyses of data requirements rules because the 

3683 Agency accounts for other registration costs such as overhead in the Information 

3684 Collection Request (ICR) for FIFRA Section 3 Registration under the Paperwork 

3685 Reduction Act. 

3686 iv. Test probabilities. EPA’s test probabilities (the probabilities of tests 

3687 being required for a registration actions) were based on a sample of 70 actual 

3688 antimicrobial registration actions out of 90 relevant new registration actions during 

3689 the six year period beginning 2000 and ending 2005, supplemented with EPA’s 

3690 scientific judgment. The time period (2000-2005) was chosen for EPA’s EA 

3691 because the analysis in the EA was started in 2006. The commenter claims to 

3692 have based the test probabilities used to make their estimates on a sample of 29 

3693 registration review cases (not new registrations) occurring between 2008 and 

3694 2010. 

3695 v. Factors which drive costs for new registrations. To determine the 

3696 influence of the previously-discussed factors on the difference between the 

3697 commenter’s and EPA’s estimates, EPA performed the following analysis on the 

3698 data requirements costs and incremental costs using the same unit test costs and 

3699 test probabilities used in the proposed rule: 
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3700  To account for the effect of the unit test costs on the data requirements 

3701 costs and incremental costs, EPA substituted the commenter’s unit test costs 

3702 without overhead into EPA’s analysis of the proposed rule using EPA’s test 

3703 probabilities and number of registrations. If there were no changes, this would 

3704 indicate that the test costs were not driving the differences in estimates. 

3705  To account for the effect of test probabilities and number of 

3706 registrations, EPA substituted the commenter’s unit test costs with overhead into 

3707 EPA’s analysis. In this case, the difference between the EPA’s and the 

3708 commenter’s analysis is contained in the test probabilities and number of 

3709 registrations. If there were no changes, this would indicate that the test 

3710 probabilities and number of registrations were not driving the differences between 

3711 the two analyses. Since the commenter includes overhead in their analysis, 

3712 overhead was included in this comparison to make other things equal so that the 

3713 differences in test probabilities and number of registrations could be isolated. 

3714 vi. Results. The results of the factor analysis are presented in Table 1. 

3715 Table 1: Comparison of Data Requirement Costs and Factors for New 

3716 Registrations 
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Column A B C D 

Unit Test Costs according to: EPA 

Proposed 

Rule 

Commenter 

without 

overhead 

Commenter 

with 30% 

overhead 

Commenter 

with 30% 

overhead 

Test Probabilities according to: EPA EPA EPA Commenter 

Number of Registrations 

according to: 

EPA EPA EPA Commenter 

Data Requirement Cost 

according to Proposed Rule ($ 

millions) 

$15.0 $19.9 $25.5 $25.9 

Cost of Proposed Rule 

(Incremental Costs) ($ millions) 

$3.9 $7.6 $9.8 $9.2 

3717 

3718 Column A exhibits the data requirements and incremental costs from EPA’s 

3719 EA of the proposed rule. In column B, the data requirements and incremental 

3720 costs are calculated using the commenter’s unit test costs without overhead costs, 

3721 but EPA’s test probabilities and number of registrations. Column C is the same as 

3722 column B, but with overhead costs included. Finally, column D exhibits the data 

3723 requirements and incremental costs with overhead as calculated by the 

3724 commenter. 

3725 The result of the first factor analysis is demonstrated by comparing column 

3726 A to column B. In this case, the difference between the two columns is the unit 

3727 test costs. Inserting the commenter’s unit test costs, without overhead, into the 

3728 cost estimates with EPA’s test probabilities and number of registrations leads to 

3729 over a 30 percent increase in data requirements cost and a nearly 100 percent 

3730 increase in incremental costs. 
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3731 The result of the second factor analysis is demonstrated by comparing 

3732 columns C and D. In this case, the difference between the two columns is in the 

3733 test probabilities and number of registrations. While individual test probabilities 

3734 may be different in EPA’s and the commenter’s analyses, the overall effect of the 

3735 products of test probabilities and number of registrations, when summed with the 

3736 unit test costs, including overhead, are similar in both of these analyses. The 

3737 resulting differences in data requirements cost and incremental costs are less 

3738 than 2 percent and about 6 percent, respectively. Therefore, EPA concludes that 

3739 any differences in test probabilities and number of registrations used as input 

3740 parameters in the calculations do not have a significant effect on the total data 

3741 requirement cost of new registrations. 

3742 Comparisons across columns A, B, and C also provide information on the 

3743 portion of the cost difference accounted for by overhead costs. Columns A, B, 

3744 and C compare the cost of data requirements using the unit test cost estimates of 

3745 EPA, and those of the commenter with and without overhead. The overhead 

3746 costs account for more than one-half of the difference in the total cost of the data 

3747 requirements, but less than 40 percent of the difference in incremental costs (the 

3748 incremental cost is the increase costs between the baseline, part 161, and 

3749 proposed part 158, subpart W). 

3750 From this comparison, EPA makes the following conclusions. First, 

3751 differences in test probabilities and number of registrations do not have a 

3752 significant impact on the cost of the rule. Second, even if EPA and the commenter 

3753 used the same probabilities and test costs, inclusion of overhead costs by the 
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3754 commenter would result in a 30 percent difference in costs. Finally, when the 

3755 overhead costs are removed from the commenter’s analysis, differences in unit 

3756 test costs between EPA and the commenter account for most of the differences in 

3757 the estimates of the cost of the rule for new registrations. 

3758 vi. Revised test costs. In light of the results of the comparison between 

3759 EPA’s and the commenter’s EA, EPA sought to verify its unit test cost estimates. 

3760 To examine the costs submitted by ACC, EPA re-surveyed the cost of conducting 

3761 studies for 30 data requirements: The criteria for selecting which test’s cost to 

3762 update included how the difference in estimates would impact on the cost of the 

3763 rule, the magnitude of the differences in estimates, and the age and source of 

3764 EPA’s estimates. EPA’s data gathering methodology is reproducible, and based 

3765 on actual data. EPA does not adjust the lab’s cost estimates, i.e., the costs are 

3766 used as obtained from the laboratory. Under the Information Quality Act (IQA), 

3767 EPA must ensure and maximize the quality, objectivity, utility, and integrity of the 

3768 data used in its analyses. 

3769 The re-surveyed test costs are used in the EA (economic analysis) for the 

3770 final rule. EPA is using its cost estimates because it has revised its most relevant 

3771 and oldest unit test cost estimates. In addition, the commenter did not provide a 

3772 basis or sufficient explanation that would meet the standards of the IQA to justify 

3773 EPA’s accepting the commenter’s costs. For additional information see response 

3774 to comment 40.1 in the Response to Comments Document and the final economic 

3775 analysis, both in the docket at http://www.regulations.gov. 

3776 B. Impact on Small Businesses 
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3777 1. Comment. A Commenter claimed that EPA underestimated costs, is not 

3778 fully complying with the Regulatory Flexibility Act (RFA) and the Small Business 

3779 Regulatory Enforcement Fairness Act (SBREFA), and must prepare an Initial 

3780 Regulatory Flexibility Assessment (IRFA). In addition, the commenter argued that 

3781 small businesses will be adversely affected, that there will be an "increased 

3782 disparity between registrants and a more uneven playing field," and finally, that a 

3783 SBREFA analysis should have been conducted. 

3784 2. EPA’s Response. EPA acknowledges that the cost of the data 

3785 requirements would likely be a larger percentage of a small business’s revenues, 

3786 but did not find that the rule would have a significant adverse economic impact on 

3787 a substantial number of small firms. 

3788 A regulatory flexibility analysis examines the type and number of small 

3789 entities potentially subject to the rule, recordkeeping and compliance 

3790 requirements, and significant regulatory alternatives, among other things. RFA, 

3791 as amended by SBREFA, requires EPA to consider the economic impact of 

3792 proposed rules on small entities. RFA requires EPA to prepare an IRFA for each 

3793 proposed rule, when the rule will have a significant economic impact on a 

3794 substantial number of small entities. 

3795 To comply with RFA, EPA did a retrospective analysis of what the 

3796 additional costs would have been on actual new registrations if the proposed rule 

3797 had been in effect during 2000-2005. This analysis did not indicate a significant 

3798 impact on a substantial number of small entities; instead, the analysis indicated 

3799 that 5 percent of small firms (25 out of 500) are likely to experience some impact 
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3800 and only 2.8 percent of small firms (14 out of 500) are likely to experience an 

3801 economic impact of 3 percent or more of gross sales. Based on this analysis, 

3802 EPA certified that the proposed rule would not have a significant adverse 

3803 economic impact on a substantial number of small firms. As a result, EPA did not 

3804 have to conduct an IRFA nor convene a SBREFA Panel for the proposed part 

3805 158, subpart W rule. 

3806 In the EA for the final rule, EPA re-estimated the SBREFA analysis with 

3807 revised unit test costs and changes in data requirements. 

3808  About 23 small firms (almost 5%) are likely to experience an economic 

3809 impact of 3% or more of gross sales, and

3810  About 26 small firms, (over 5%) are likely to experience an economic 

3811 impact of 1% or more of gross sales.

3812 Hence, had these results been estimated at the proposal stage, EPA would still 

3813 have concluded that there would not be a significant impact on a substantial 

3814 number of small entities. 

3815 C. Cost of New Data Requirements on Registration Review

3816 1. Comment. A commenter stated that EPA has not accurately stated the 

3817 potential costs and benefits, as required by Executive Order (EO) 12866. In 

3818 particular, EPA has not included the impact of incremental costs of new data 

3819 requirements on registration review, or the cost of consultations. The commenter 

3820 also claims that under the PRA, EPA should include the paperwork burden costs 

3821 of registration review for existing registrants. 

3822 2. EPA’s Response. EO 12866 requires the Agency to submit to OMB for 

3823 review significant regulatory actions. EPA complied with EO 12866 during 2008 
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3824 by submitting drafts of both the economic analysis and the proposed rule to OMB. 

3825 The changes that were made to the proposed rule as the result of OMB’s review 

3826 were included in the docket for the proposed rule at http://www.regulations.gov. 

3827 The Agency notes that one purpose of soliciting comments on the economic 

3828 analysis at the proposal stage is to get input on where the Agency might improve 

3829 the economic analysis. 

3830 The commenter is not correct in asserting that EPA did not include the 

3831 impact of incremental costs. The Agency has captured the anticipated costs 

3832 necessary for complying with the regulations. See the final Economic Analysis 

3833 (Ref. 13) in the docket at http://www.regulations.gov for a more detailed 

3834 discussion, particularly sections 5.3 and 5.5. 

3835 The commenter is correct in that the costs of fulfilling the 11 “new” data 

3836 requirements during registration review were not considered in the Agency’s 

3837 economic analysis of the proposed part 158, subpart W data requirements. EPA 

3838 agrees with the commenter that registrants of existing antimicrobial products will 

3839 incur costs during registration review. In fact, EPA relied on the 2005 EA 

3840 conducted for the Registration Review Rule. When registration review was 

3841 proposed, EPA prepared an economic analysis of that program, which estimated 

3842 the cost of data requirements and paperwork burden according to what would 

3843 likely be required in registration review for existing registrants. The 2005 

3844 registration review EA estimate of data requirement costs for existing antimicrobial 

3845 pesticides was based on what would likely be required for a sample of 

3846 antimicrobial active ingredients. This would have included all tests that would 
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3847 have been required at that time, i.e., those in current practice whether or not in 

3848 part 158. 

3849 However, the proposed part 158, subpart W included “new” tests, which 

3850 were not anticipated when the economic analysis of the registration review 

3851 process was completed. In a final economic analysis for part 158, subpart W, EPA 

3852 addresses the additional registration review costs for these 11 “new” studies, as 

3853 well as other changes from the proposed to final rule including changes made as 

3854 a result of the comments received. The incremental impact for Registration 

3855 Review is $ 6.8 M. 

3856 The commenter is also correct that EPA did not include the cost of 

3857 consultation in its economic analysis. Consultations are longstanding, commonly 

3858 used, and valuable processes in EPA’s Pesticide Program and are beneficial to 

3859 both EPA and the applicants. However, consultations are not mandatory, and 

3860 based on comments received EPA has removed all references to consultations 

3861 from the final data requirements tables. See Unit V.C for additional information on 

3862 the use and purpose of consultations. 

3863 XXIII. References 

3864 As indicated under ADDRESSES, a docket has been established for this 

3865 rulemaking under docket ID number EPA-HQ-OPP–2008–0110. The following is 

3866 a listing of the documents that are specifically referenced in this proposed rule. 

3867 The docket includes these documents and other information considered by EPA in 

3868 developing this rule, including documents that are referenced within the 

3869 documents that are included in the docket, even if the referenced document is not 
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3870 physically located in the docket. For assistance in locating documents, please 

3871 consult the technical contact listed under FOR FURTHER INFORMATION 

3872 CONTACT. 

3873 Ref. 1: Rule Text of “Data Requirements for Pesticide Registration; Final Rule;” 

3874 (49 FR 42856). 

3875 Ref. 2: ACC Biocides Panel; “Regulation of Antimicrobials that are Indirect or 

3876 Secondary Direct Food Additives;” (February 2, 2006). 

3877 Ref. 3: ACC Biocides Panel; “Comments on EPA’s September 17, 1999 

3878 Proposed Rule on Registration Requirements for Antimicrobial Pesticide Products 

3879 and Other Pesticide Regulatory Changes for Codification; (January 18, 2000). 

3880 Ref. 4: ACC Biocides Panel; Memorandum to Frank Sanders, “EPA’s Current 

3881 Interpretation of the Antimicrobial Reform Technical Corrections Act and Section 

3882 2(bb) of FIFRA is Inconsistent with the Statutes;” (August 3, 2000). 

3883 Ref. 5: ACC Biocides Panel; “EPA/FDA Jurisdiction for Food Contact Antimicrobials;” 

3884 (July 17, 2003). 

3885 Ref. 6: Grizzle, Charles L.; representative of Albright & Wilson Americas, Inc., 

3886 letter to Lynn R. Goldman; (September 11, 1997). 

3887 Ref. 7: ChemReg International, L.L.C.; Tiered Testing for Risk Assessment of 

3888 Antimicrobial Pesticides; (September 12, 2002). 

3889 Ref. 8: Goldberg, Seth; “Section 2(bb) of FIFRA; Dual Jurisdiction Over Food Contact 

3890 Antimicrobials; (April 27, 2001). 

3891 Ref. 9: ACC Biocides Panel; “Comments on The Preliminary Risk Assessment for 1,4-

3892 Bis(bromoacetoxy)-2-butene (BBAB);” (August 6, 2001). 
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3893 Ref. 10: ACC Biocides; Hasmukh C. Shah letter to Frank T. Sanders; (August 3, 

3894 2000). 

3895 Ref. 11: Edwards, Deborah; OPP Response to CropLife letter of May 29, 2009; 

3896 (June 26, 2009). 

3897 Ref. 12: Portier; SAP Waiver; (April 4, 2011). 

3898 Ref. 13: USEPA; Final Economic Analysis of Changes in Data Requirements for 

3899 Antimicrobial Pesticides (update date after OMB review). 

3900 XXIV. FIFRA Review Requirements 

3901 In accordance with FIFRA section 25(a), a draft of this final rule was 

3902 submitted to the FIFRA Scientific Advisory Panel (SAP). EPA requested the 

3903 FIFRA SAP to waive its review of the final rule based on fact that the SAP, in 

3904 2008, had waived review of the proposed rule: The final rule does not contain any 

3905 new scientific issues warranting additional review by the SAP. The SAP waived 

3906 its review on April 4, 2011, stating that “[t]he final rule does not contain scientific 

3907 issues that the Panel has not previously considered” (Ref. 12). 

3908 In accordance with FIFRA section 25(a), EPA has submitted a draft of the 

3909 final rule to the appropriate Congressional Committees and the Secretary of the 

3910 Department of Agriculture. There were no comments in response to these 

3911 submissions. 

3912 In accordance with FIFRA section 21(b), EPA submitted a draft of the final 

3913 rule to the Secretary of Health and Human Services (HHS). Their comments on 

3914 the draft of the final rule included requests to expand further the discussion on 

3915 “the differentiation of authorities of the Food [and] Drug Administration (FDA) and 
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3916 EPA on regulation of antimicrobial pesticides when present in food,” and also, 

3917 various edits were requested by FDA’s Office of General Counsel (OGC). In 

3918 response, EPA has expanded the differentiation discussion and made various 

3919 edits. Both EPA’s OGC and FDA’s OGC vetted the changes. 

3920 HHS also requested that EPA further clarify the “guidance for product 

3921 registrants in using emerging alternate test methods in evaluation of toxicity.” 

3922 EPA agrees that because the science is changing rapidly, continuous 

3923 communication with stakeholders will be important to their understanding of the 

3924 availability of alternate test methods that OPP would consider. OPP established 

3925 the PPDC workgroup on 21st Century Toxicology to support this communication. 

3926 Information on OPP's transition to alternate methods is available on EPA's 

3927 website on OPP’s 21st Century toxicology vision and strategy webpage, which 

3928 contains a tools matrix that describes plans to incorporate new scientific tools. 

3929 FDA also noted that “the data requirements do not appear to consider 

3930 impacts of the proposed pesticide use on antimicrobial resistance development.” 

3931 As discussed in the proposed rule, EPA is a participant on the Interagency Task 

3932 force on Antimicrobial Resistance. While the focus of this group is on the use of 

3933 antibiotics, the Antimicrobials Division (AD) has participated in the taskforce 

3934 efforts by providing review and comment on documents related to antimicrobial 

3935 resistance, specifically, the reports of the Codex Ad Hoc Intergovernmental Task 

3936 Force on Antimicrobial Resistance, issued through the Codex Alimentarius 

3937 Commission. AD also conducted a literature search into the use of antimicrobial 

3938 pesticides and the development of resistant bacteria. While this literature search 
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3939 is several years old, AD does not believe that there have been substantial 

3940 changes since the search was conducted. 

3941 The results of the literature search did not support a finding that the use of 

3942 antimicrobial pesticides leads to development of resistant bacteria. EPA does 

3943 consider the impacts of a pesticide's use on the development of antimicrobial 

3944 resistance. However, EPA is unaware of a data requirement approach that would 

3945 fit this circumstance. Antimicrobial resistance develops in the environment during 

3946 use, or as a result of the use when the micro-organisms that are still present 

3947 "swap their genetic material." The efficacy studies required as part of the 

3948 application submission provide information on the product's ability to kill or 

3949 deactivate the micro-organism when used according to the directions on the 

3950 product. Historically, the concentration of the antimicrobial in the product is set 

3951 well-over the minimum inhibitory concentration, to assure that the micro-organism 

3952 is killed or deactivated. If information indicated that an antimicrobial product was 

3953 not performing effectively, then it is likely that the manufacturer would request an 

3954 amendment to their registration to increase the concentration of the antimicrobial 

3955 in the product. EPA has been unable to determine to what extent there is a 

3956 problem of antimicrobial resistance or what data submitted as part of a registration 

3957 package could predict the environmental conditions for developing resistance in 

3958 the future. EPA therefore watches, monitors, and mitigates, as needed. 

3959 XXV. Statutory and Executive Order Reviews

3960 A. Regulatory Planning and Review 
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3961 Under Executive Order 12866, entitled Regulatory Planning and Review 

3962 (58 FR 51735; October 4, 1993), this action is a “significant regulatory action” 

3963 because this action might raise novel legal or policy issues arising out of legal 

3964 mandates, the President’s priorities, or the principles set forth in the Executive 

3965 Order. Accordingly, EPA submitted this action to the Office of Management and 

3966 Budget (OMB) for review under Executive Orders 12866 and 13563, entitled 

3967 Improving Regulation and Regulatory Review (76 FR 3821; January 21, 2011). 

3968 Any changes made in response to OMB recommendations have been 

3969 documented in the docket for this action. 

3970 EPA has prepared an EA of the potential costs associated with this action, 

3971 entitled “Final Economic Analysis of Changes in Data Requirements for 

3972 Antimicrobial Pesticides” (Ref. 13), a copy of which is in the docket at 

3973 http://www.regulations.gov. This final EA evaluates the potential benefits and 

3974 costs expected as a result of registrations and registration reviews. The EA is 

3975 briefly summarized here. 

3976 In its analysis, the Agency considered the potential, additional costs for the 

3977 registration of new antimicrobial pesticides or new uses of currently registered 

3978 antimicrobial pesticides, as well as the potential, additional costs incurred during 

3979 the registration review of existing antimicrobial pesticides. 

3980 Based on comments received during the public comment period, the 

3981 following changes were made to the rulemaking, and are therefore reflected in the 

3982 final EA: 
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3983  One proposed data requirement will not be codified: Non-dietary 

3984 ingestion exposure. The test cost is $75,000. In the proposed rule, EPA 

3985 expected to receive the test 0.8 times per year, representing an annual industry 

3986 savings of $63, 125.

3987  EPA revised certain of the data requirements from “NR” or “CR” to “R,” 

3988 or vice-versa. 

3989  Based on comments received, three new data requirements were 

3990 added: Simulation test to assess the biodegradability of chemicals discharged in 

3991 wastewater, simulation test – aerobic sewage treatment: activated sludge units, 

3992 and nature of the residue on surfaces. The rationale for these three new studies 

3993 is described in Unit III.D. 

3994 The estimated costs for both registration review and for a registration 

3995 action for the three newly-required data requirements are: 

3996 1. Simulation tests to assess the biodegradability of chemicals in 

3997 discharged wastewater and simulation test – aerobic sewage treatment: activated 

3998 sludge units. Both of these studies are used as part of the down-the-drain 

3999 analysis for antimicrobials. The studies are conditionally required for all use 

4000 patterns, except for the aquatic areas use pattern, for which the study is not 

4001 required. EPA does not have an estimate for the cost of either of these studies; 

4002 instead, for the EA, EPA used the value $33,000, which is the cost of the porous 

4003 pot test. The Agency expects, however, that the cost of the simulation tests will 

4004 be less than this amount. For registration review, EPA expects to receive the 

4005 porous pot test or one of the simulation tests up to 8.5 times per year, for an 
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4006 annual industry cost of $280,500. For new registrations, EPA expects to receive 

4007 either of the studies up to 7.5 times per year, for an annual industry cost of 

4008 $247,500. The total annual cost is $528,000. 

4009 2. Nature of residue on surfaces. This test is part of the residue chemistry 

4010 data requirements, and is conditionally required for all use pattern categories. The 

4011 test cost is $95,000. For registration review, EPA expects to receive this test 1.3 

4012 times per year, for an annual industry cost of $118,750. For new registrations, 

4013 EPA expects to receive this test up to 0.5 times per year, for an annual industry 

4014 cost of $44,333. The total annual cost is $163,083.

4015 Many test notes for data requirements were revised based on comments 

4016 received. Data requirements for certain use patterns were changed from “NR” or 

4017 “CR” to “R,” while others were changed from “R” to “CR.” Because the cost of the 

4018 rule depends, in part, on the probabilities of the tests being required, these 

4019 revisions have resulted in a modification of the cost of the rule. Instead of 

4020 estimating the cost of each change individually, the Agency re-estimated the 

4021 potential cost of the regulation as a whole, taking into account the changes 

4022 discussed above. 

4023 Based on comments received, EPA has updated the unit test costs for 30 

4024 selected tests. The criteria for selecting which test’s cost to update included: 

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

4026  The magnitude of the difference between EPA’s cost estimate and the 

4027 commenters’ cost estimate, and 

4028  The length of time since EPA’s cost estimate was last updated. 
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4029 EPA estimated the annual cost of registering a new antimicrobial pesticide 

4030 or new use of currently-registered antimicrobial pesticides, taking into account 

4031 both the changes in data requirements and in unit test costs. Both the total 

4032 annual industry costs and the newly-imposed costs were estimated. The updated 

4033 test costs plus exposure and other test costs revisions since the proposed rule 

4034 increased the cost of the rule by about 23 percent compared to the proposed rule. 

4035 The estimated total annual industry costs of the final rule is expected to be about 

4036 $19.3 million, which is approximately 29 percent higher than the cost of the 

4037 proposed rule. The difference between the baseline costs (the existing data 

4038 requirements that were codified in 1984) and the cost of the Agency’s current 

4039 practices is about $1 million annually. The difference between the baseline costs 

4040 and the final rule costs, i.e., the incremental costs is approximately $8.2 million 

4041 annually. Under the final rule, the average cost per registration action of a new 

4042 antimicrobial active ingredient is approximately $1 million to $5 million. 

4043 For existing chemicals, data requirements in part 158 subpart W are 

4044 relevant to the registration review program which began to replace the 

4045 reregistration program in 2006 as a means of systematically reevaluating existing 

4046 registrations against the standards of FIFRA. 

4047 EPA has evaluated the impact of the data requirements being codified 

4048 today on registrants of existing chemicals undergoing registration review whose 

4049 active ingredient databases do not contain all of the new data requirements. The 

4050 average additional cost of registration review as a result of the new data 

4051 requirements is estimated to be about $588,000 for wood preservatives, $284,000 
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4052 for food and indirect food uses, and $260,000 for all other uses. For registration 

4053 review, the total annual cost is $6.8 million. 

4054 As required, EPA conducted an analysis of the impact of this final rule on 

4055 small businesses, as discussed in the Unit XXV.C. 

4056 B. Paperwork Burdens 

4057 The information collection requirements contained in this rule have been 

4058 submitted for approval to OMB under the Paperwork Reduction Act (PRA), 44 

4059 U.S.C. 3501 et seq. At the time of the proposed rule, EPA prepared a supporting 

4060 statement for amending an ICR), entitled “Data Requirements for Antimicrobial 

4061 Pesticides (Proposed Rule)” and identified by EPA ICR No. 2318.01, a copy of 

4062 which is in the docket at http://www.regulations.gov. 

4063 Under PRA, “burden” means the total time, effort, or financial resources 

4064 expended by persons to generate, maintain, retain, or disclose or provide 

4065 information to or for a Federal agency. 

4066 The information collection activities related to the submission of data to 

4067 EPA in order to register, amend or retain a new or existing pesticide product or 

4068 obtain a tolerance for that product are already approved by OMB under PRA. As 

4069 such, the supporting statement only addresses the proposed changes to the data 

4070 requirements that impact the information collection activities related to 

4071 antimicrobial pesticides. The procedures for submitting data to EPA under FIFRA 

4072 and FFDCA are not changed in this proposal, and are already approved by OMB 

4073 in the following ICRs: 
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4074  Tolerance ICR. Data Submission Activities Associated with 

4075 Tolerance Actions (currently approved under OMB Control No. 2070-0024 (EPA 

4076 ICR No. 0597)); 

4077  Registration ICR. Data Submission Activities Associated with the 

4078 Application for a New or Amended Registration of a Pesticide (currently approved 

4079 under OMB Control No. 2070-0060 (EPA ICR No. 0277)); and 

4080  Reregistration, Special and Registration Review ICR. Data 

4081 Submission Activities Associated with the Generation of Data for Special Review 

4082 or Registration Review (currently approved under OMB Control No. 2070-0174 

4083 (EPA ICR No. 2288)). 

4084 These three program activities are an integral part of the Agency’s 

4085 pesticide program, including antimicrobial pesticides, and the corresponding ICRs 

4086 are regularly renewed every 3 years as required by PRA. The total estimated 

4087 average annual public reporting burden currently approved by OMB for these 

4088 various activities range from 8 hours to approximately 3,000 hours per 

4089 respondent, depending on the activity and other factors surrounding the particular 

4090 pesticide product. 

4091 In the supporting statement the Agency estimates that the typical, current 

4092 annual paperwork burden for registrants per antimicrobial pesticide registration is 

4093 194 burden hours and $12,631. The total annual registrant paperwork burden 

4094 and costs for data submission activities for antimicrobial pesticides applicants and 

4095 registrants will be updated accordingly in the ICRs specified above during the 

4096 next, appropriate ICR renewal cycle. 
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4097 An agency may not conduct or sponsor, and a person is not required to 

4098 respond to an information collection request unless it displays a currently valid 

4099 OMB control number, or is otherwise required to submit the specific information by 

4100 a statute. The OMB control numbers for EPA’s regulations codified in Title 40 of 

4101 the Code of Federal Regulations, after appearing in the preamble of the final rule, 

4102 are further displayed either by publication in the Federal Register or by other 

4103 appropriate means, such as on the related collection instrument or form, if 

4104 applicable. The display of OMB control numbers for certain EPA regulations is 

4105 consolidated in a list at 40 CFR 9.1. 

4106 C. Small Entity Impacts

4107 The Regulatory Flexibility Act generally requires an Agency to prepare a 

4108 regulatory flexibility analysis of any rule subject to notice and comment rulemaking 

4109 requirements under the Administrative Procedure Act or any other statute unless 

4110 the agency certifies that the rule will not have a significant economic impact on a 

4111 substantial number of small entities. Small entities include small businesses, small 

4112 organizations and small governmental jurisdictions.

4113 For purposes of assessing the impacts of today's rule on small entities, 

4114 small entity is defined as: (1) a small business as defined by the Small Business 

4115 Administration’s (SBA) regulations at 13 CFR 121.201, which is based on either 

4116 the maximum number of employees or on the sales for small businesses in each 

4117 industry sector, as defined by a 6-digit NAICS code, and for this rule is a producer 

4118 of pesticide products (NAICS 32532), antifoulants (NAICS 32551), antimicrobial 

4119 pesticides (NAICS 32561) or wood preservatives (NAICS 32519), importers of 
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4120 such products, or any person or company who seeks to register an antimicrobial, 

4121 antifoulant coating, ballast water treatment, or wood preservative pesticide or to 

4122 obtain a tolerance for such a pesticide; (2) a small governmental jurisdiction that is 

4123 a government of a city, county, town, school district or special district with a 

4124 population of less than 50,000; or (3) a small organization that is any not-for-profit 

4125 enterprise which is independently owned and operated and is not dominant in its 

4126 field. 

4127 After considering the economic impacts of this final rule on small entities, I 

4128 certify that this action will not have a significant adverse economic impact on a 

4129 substantial number of small entities. The factual basis for the Agency’s 

4130 determination is presented in the small entity impact analysis prepared as part of 

4131 the Economic Analysis for this final rule (Ref. 13), which is available in the docket 

4132 at http://www.regulations.gov. EPA has determined that this rulemaking does not 

4133 impact any small governmental jurisdictions or any small non-for-profit enterprise 

4134 because these entities are rarely pesticide applicants or registrants. As such, 

4135 EPA has assessed the impacts on small businesses. Some of the small entities 

4136 directly regulated by this rulemaking are in the pesticide and other agricultural 

4137 chemical manufacturing industry sector (NAICS code 325320). Firms in this sector 

4138 are considered small under the SBA definition if they employ 500 or fewer people. 

4139 The economic analysis for the final rule specifies the NAICS code used for each 

4140 of the firms analyzed. 

4141 EPA estimates that 750 unique parent companies constitute the total 

4142 universe of pesticide antimicrobial registrants. Of these, based on the SBA 
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4143 definition of a small business and the available sales data for these firms, EPA 

4144 estimates that 500, or approximately 67 percent, qualify as a small business. 

4145 When considering both registration review and new registrations, on average 

4146 each year about 30 small businesses would have incurred additional costs under 

4147 this rule. EPA estimates that: 

4148 C. About 23 small firms (almost 5 percent) subject to this regulation are likely 

4149 to experience an economic impact of 3 percent or more of gross sales, 

4150  About 3 small firms (0.6 percent) subject to this regulation are likely to 

4151 experience an economic impact of greater than 1 percent but less than 3 percent 

4152 of sales revenues, and 

4153  About 3 small firms (0.6 percent) subject to this regulation are likely to 

4154 experience an economic impact of greater than 0 percent, but less than 1 percent 

4155 of sales revenues. 

4156 In addition, there are also opportunities for small entities to lower their 

4157 potential costs. The proposed data requirements in many instances are tiered, 

4158 with higher-tiered testing triggered on the results of lower-tiered testing. EPA 

4159 encourages registrants to consult with the Agency to ensure that only the required 

4160 data is submitted. If available, open literature or the same tests on similar 

4161 products, or alternative means to meet data requirements, such as QSAR, can be 

4162 submitted for Agency consideration. Some firms may have surrogate data or they 

4163 may share the cost of generating data. These may present opportunities for cost 

4164 savings by small entities, and all other applicants as well, while allowing the 
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4165 Agency to fulfill its role of making pesticide regulatory decisions that protect the 

4166 general population, sensitive sub-populations, and the environment. 

4167 This rule was proposed on October 8, 2008. Small entities were able to 

4168 provide comments during the 90 day public comment period, which was extended 

4169 an additional 90 days at the request of stakeholders. On November 6, 2008, EPA 

4170 convened a public workshop to explain the provisions of the proposed rule, 

4171 arranging for the workshop to be webcast for those who could not attend the 

4172 public workshop in person. 

4173 D. Unfunded Mandates 

4174 Under Title II of the Unfunded Mandates Reform Act of 1995 (UMRA) (2 

4175 U.S.C. 1531-1538), EPA has determined that this final rule does not contain a 

4176 Federal mandate that may result in expenditures of $100 million or more for State, 

4177 local, and tribal governments, in the aggregate, or the private sector in any one 

4178 year. As described in Unit XXV.A, the incremental costs for this final rule is 

4179 estimated at approximately $8.3 million (for registration actions) and $6.8 million 

4180 (for registration review) per year for the private sector, which is below the $100 

4181 million threshold. Since State, local, and tribal governments are rarely pesticide 

4182 applicants, this rule is not expected to significantly or uniquely affect small 

4183 governments. Accordingly, this rule is not subject to the requirements of sections 

4184 202 and 205 of UMRA. 

4185 This rule is also not subject to the requirements of section 203 of UMRA 

4186 because it contains no regulatory requirements that might significantly or uniquely 
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4187 affect small governments. As stated above, State, local, and tribal governments 

4188 are rarely pesticide applicants. 

4189 E. Federalism 

4190 This action does not have federalism implications, because it will not have 

4191 substantial direct effects on the States, on the relationship between the national 

4192 government and the States, or on the distribution of power and responsibilities 

4193 among the various levels of government, as specified in Executive Order 13132 

4194 (64 FR 43255; August 10, 1999). Since States or local governments are rarely 

4195 pesticide applicants or registrants, this final rule would seldom affect a State or 

4196 local government. Thus, Executive Order 13132 does not apply to this rule. 

4197 In the spirit of Executive Order 13132 and consistent with EPA policy to 

4198 promote communication between EPA, and State and local governments, EPA 

4199 specifically solicited comment on the proposed rule from State and local officials. 

4200 EPA did receive comments on substantive parts from local sanitation districts and 

4201 associations representing their interests. Their comments are addressed in the 

4202 Response to Comments Document in the docket at http://www.regulations.gov, 

4203 and, as appropriate, revisions were made for the final rule. 

4204 F. Indian Tribal Government Implications

4205 This action does not have tribal implications, as specified in Executive 

4206 Order 13175 (65 FR 67249, November 9, 2000). At present, no tribal government 

4207 holds, or has applied for, a pesticide registration. Thus, Executive Order 13175 

4208 does not apply to this action. In the spirit of the Order, and consistent with EPA 

4209 policy to promote communications between the Agency and Indian tribes, EPA 
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4210 specifically solicited comment on the proposed rule from tribal officials. No 

4211 comments were received. 

4212 G. Protection of Children’s Health 

4213 This final rule is not subject to Executive Order 13045, entitled Protection of 

4214 Children from Environmental Health Risks and Safety Risks (62 FR 19885, April 

4215 23, 1997) because it is not economically significant as defined by Executive Order 

4216 12866, and because the Agency does not have reason to believe the 

4217 environmental health or safety risks addressed by this action present a 

4218 disproportionate risk to children. This rule does not propose an environmental 

4219 standard that is intended to have a negatively disproportionate effect on children. 

4220 To the contrary, this rule is intended to provide added protection to children from 

4221 antimicrobial pesticide risk. EPA will use the data and information obtained by 

4222 this action to carry out its mandate under FFDCA to give special attention to the 

4223 risks of pesticides to sensitive groups in early lifestages, especially infants and 

4224 children. 

4225 H. Executive Order 13211: Actions Concerning Regulations that Significantly 

4226 Affect Energy Supply, Distribution, or Use 

4227 This final rule is not subject to Executive Order 13211, entitled Actions 

4228 Concerning Regulations that Significantly Affect Energy Supply, Distribution, or 

4229 Use (6 FR 28355, May 22, 2001) because it is not an economically significant 

4230 regulatory action under Executive Order 12866, and it is not likely to have any 

4231 adverse effect on the supply, distribution, or use of energy. 

4232 I. National Technology Transfer and Advancement Act 
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4233 Section 12(d) of the National Technology Transfer and Advancement Act of 

4234 1995 (“NTTAA”), Public Law No. 104-113, 12(d) (15 U.S.C. 272 note) directs EPA 

4235 to use voluntary consensus standards in its regulatory activities unless to do so 

4236 would be inconsistent with applicable law or otherwise impractical. Voluntary 

4237 consensus standards are technical standards (e.g., materials specifications, test 

4238 methods, sampling procedures, and business practices) that are developed or 

4239 adopted by voluntary consensus standards bodies. NTTAA directs EPA to 

4240 provide Congress, through OMB, explanations when the Agency decides not to 

4241 use available and applicable voluntary consensus standards. This action does not 

4242 involve technical standards. Therefore, EPA did not consider the use of any 

4243 voluntary consensus standards. 

4244 J. Environmental Justice 

4245 Executive Order 12898 entitled Federal Actions to Address Environmental 

4246 Justice in Minority Populations and Low Income Populations (59 FR 7629; 

4247 February 16, 1994) establishes federal executive policy on environmental justice. 

4248 Its main provision directs Federal agencies, to the greatest extent practicable and 

4249 permitted by law, to make environmental justice part of their mission by identifying 

4250 and addressing, as appropriate, disproportionately high and adverse human 

4251 health or environmental effects of their programs, policies, and activities on 

4252 minority populations and low-income populations in the United States. 

4253 EPA has determined that this final rule will not have disproportionately high 

4254 and adverse human health or environmental effects on minority or low-income 

4255 populations because it increases the level of environmental protection for all 
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4256 affected populations without having any disproportionately high and adverse 

4257 human health or environmental effects on any population, including any minority 

4258 or low-income population. This rule only impacts entities that intend to register or 

4259 currently hold a registration for an antimicrobial pesticide. 

4260 XXVI. Congressional Review Act 

4261 The Congressional Review Act, 5 U.S.C. 801 et seq., generally provides 

4262 that before a rule may take effect, the Agency promulgating the rule must submit a 

4263 rule report to each House of the Congress and the Comptroller General of the 

4264 United States. EPA will submit a report containing this rule and other required 

4265 information to the U.S. Senate, the U.S. House of Representatives, and the 

4266 Comptroller General of the United States prior to publication of the rule in the 

4267 Federal Register. This rule is not a “major rule” as defined by 5 U.S.C. 804(2). 

4268 

4269 
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4270 List of Subjects in 40 CFR Part 158 

4271 Environmental protection, Administrative practice and procedure, 

4272 Agricultural commodities, Pesticides and pests, Reporting and record keeping 

4273 requirements. 

4274 List of Subjects in 40 CFR Part 161 

4275 Environmental protection, Administrative practice and procedure, 

4276 Agricultural commodities, Pesticides and pests, Reporting and record keeping 

4277 requirements. 

4278 Dated: ______________ 

4279 ______________________ 

4280 Administrator 
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4281 Therefore, 40 CFR part 158 and part 161 are amended as follows: 

4282 

4283 1. The authority citation for part 158 continues to read as follows: 

4284 Authority: 7 U.S.C. 136-136y and 21 U.S.C. 346a. 

4285 2. Revise § 158.1(c)(4) to read as follows: 

4286 § 158.1 Purpose and scope. 

4287 ***** 

4288 (c) *** 

4289 (4) Antimicrobial pesticides. Subparts A, B, C, D, and W of this part apply 

4290 to antimicrobial pesticides. 

4291 3. In § 158.100 revise the heading of paragraph (a); revise paragraph (b); 

4292 redesignate paragraph (c) as paragraph (e); and add new paragraphs (c) and (d) 

4293 to read as follows: 

4294 § 158.100. Pesticide use patterns. 

4295 (a). General use patterns for conventional, biochemical, and microbial 

4296 pesticides. *** 

4297 (b) Pesticide use site index for conventional, biochemical, and microbial 

4298 pesticides. The Pesticide Use Site Index for Conventional, Biochemical, and 

4299 Microbial Pesticides is a comprehensive list of specific pesticide use sites. The 

4300 index is alphabetized separately by site for all agricultural and all nonagricultural 

4301 uses. The Pesticide Use Site Index associates each pesticide use site with one or 

4302 more of the 12 general use patterns. It may be used in conjunction with the data 

4303 tables to determine the applicability of data requirements to specific uses. The 

4304 Pesticide Use Site Index for Conventional, Biochemical, and Microbial Pesticides 

4305 will be updated periodically, and is available from the Agency or may be obtained 

4306 from the Agency's website at http://www.epa.gov/pesticides. 

4307 (c) Antimicrobial pesticide use patterns. The general use patterns for 

4308 antimicrobial pesticides are described in § 158.2201. 
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4309 (d) Pesticide use site index for antimicrobial pesticides. The Pesticide Use 

4310 Site Index for Antimicrobial Pesticides is a comprehensive list of specific 

4311 antimicrobial use sites. The index is alphabetized by antimicrobial use sites, and 

4312 associates each antimicrobial use site with one or more of the antimicrobial use 

4313 patterns. It may be used in conjunction with the data tables to determine the 

4314 applicability of data requirements to specific uses. The Pesticide Use Site Index 

4315 for Antimicrobial Pesticides will be updated periodically, and is available from the 

4316 Agency or may be obtained from the Agency’s website at 

4317 http://www.epa.gov/pesticides. 

4318 (e) *** 

4319 §158.400 [Amended] 

4320 4. In the table in § 158.400(d) remove the category “Efficacy of 

4321 Antimicrobial Agents,” and all of the entries under that category. 

4322 5. Part 158 is amended by revising subpart W to read as follows: 

4323 Subpart W--Antimicrobial Pesticide Data Requirements 

4324 Sec. 

4325 §158.2200 Applicability. 

4326 §158.2201 Antimicrobial use patterns. 

4327 §158.2203 Definitions. 

4328 §158.2204 Public health and nonpublic health claims. 

4329 §158.2210 Product chemistry. 

4330 §158.2220 Product performance. 

4331 §158.2230 Toxicology. 

4332 §158.2240 Nontarget organisms. 
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4333 §158.2250 Nontarget plant protection. 

4334 §158.2260 Applicator exposure. 

4335 §158.2270 Post-application exposure. 

4336 §158.2280 Environmental fate. 

4337 §158.2290 Residue chemistry. 

4338 § 158.2200 Applicability. 

4339 Part 158, subpart W establishes data requirements for any pesticide 

4340 product that is: 

4341 (a) A pesticide that is intended for use as an “antimicrobial pesticide” 

4342 within the meaning of FIFRA sec. 2(mm)(1)(A), regardless of whether it also 

4343 meets the criterion of FIFRA sec. 2(mm)(1)(B). That criterion excludes from the 

4344 definition any antimicrobial product that is intended for a food-use requiring a 

4345 tolerance or exemption under FFDCA sec. 408 or a food additive regulation or 

4346 clearance under FFDCA sec. 409. EPA will apply this subpart to all products 

4347 intended for an antimicrobial use, purpose or function; the exclusion in FIFRA sec. 

4348 2(mm)(1)(B) does not exclude products from the data requirements of this 

4349 subpart. 

4350 (b) A product that bears both antimicrobial and non-antimicrobial uses or 

4351 claims. Such a product is subject to the data requirements for pesticides in 

4352 subparts C – O, and U or V of this part with respect to its non-antimicrobial uses 

4353 and claims, and to the requirements of this subpart W with respect to its 

4354 antimicrobial uses and claims.

4355 (c) A wood preservative, including a product that is intended to prevent 

4356 wood degradation problems due to fungal rot or decay, sapstain, or molds. 
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4357 (d) An antifoulant, including a product that is intended to kill or repel 

4358 organisms that can attach to underwater surfaces, such as boat bottoms. 

4359 § 158.2201 Antimicrobial use patterns.

4360 (a) Antimicrobial use patterns. The 12 general use patterns used in the 

4361 data tables in this subpart are: 

4362 (1) Agricultural premises and equipment. 

4363 (2) Food-handling/storage establishments, premises and equipment. 

4364 (3) Commercial, institutional and industrial premises and equipment. 

4365 (4) Residential and public access premises. 

4366 (5) Medical premises and equipment. 

4367 (6) Human drinking water systems. 

4368 (7) Materials preservatives. 

4369 (8) Industrial processes and water systems. 

4370 (9) Antifoulant paints and coatings. 

4371 (10) Wood preservatives. 

4372 (11) Swimming pools. 

4373 (12) Aquatic areas. 

4374 (b) Use site index. The Pesticide Use Site Index for Antimicrobial 

4375 Pesticides is a comprehensive list of specific antimicrobial use sites. The Index 

4376 associates antimicrobial use sites with one or more of the 12 antimicrobial use 

4377 patterns. It is to be used in conjunction with the data tables in this subpart to 

4378 determine the applicability of data requirements to specific uses. The 

4379 Antimicrobial Pesticide Use Site Index, which will be updated periodically, is 
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4380 available from the Agency or may be obtained from the Agency’s website at 

4381 http://www.epa.gov/pesticides. 

4382 § 158.2203 Definitions. 

4383 Definitions. The following terms are defined for the purposes of this subpart: 

4384 Disinfectant means a substance, or mixture of substances, that destroys or irreversibly 

4385 inactivates bacteria, fungi and viruses, but not necessarily bacterial spores, in the inanimate 

4386 environment. 

4387 Fungicide means a substance, or mixture of substances, that destroys fungi (including 

4388 yeasts) and fungal spores pathogenic to man or other animals in the inanimate environment. 

4389 Microbiological water purifier means any unit, water treatment product or system that 

4390 removes, kills or inactivates all types of disease-causing microorganisms from the water, including 

4391 bacteria, viruses and protozoan cysts, so as to render the treated water safe for drinking. 

4392 Sanitizer means a substance, or mixture of substances, that reduces the bacteria population 

4393 in the inanimate environment by significant numbers, (e.g., 3 log10 reduction) or more, but does 

4394 not destroy or eliminate all bacteria. Sanitizers meeting Public Health Ordinances are used on 

4395 food contact surfaces and are termed sanitizing rinses. 

4396 Sterilant means a substance, or mixture of substances, that destroys or eliminates all forms 

4397 of microbial life in the inanimate environment, including all forms of vegetative bacteria, bacterial 

4398 spores, fungi, fungal spores, and viruses. 

4399 Tuberculocide means a substance, or mixture of substances, that destroys or irreversibly 

4400 inactivates tubercle bacilli in the inanimate environment. 

4401 Virucide means a substance, or mixture of substances, that destroys or irreversibly 

4402 inactivates viruses in the inanimate environment. 

4403 § 158.2204 Public health and nonpublic health claims. 

4404 (a) Public health claim. An antimicrobial pesticide is considered to make a public health 

4405 claim if the pesticide product bears a claim to control pest microorganisms that pose a threat to 
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4406 human health, and whose presence cannot readily be observed by the user, including but not 

4407 limited to, microorganisms infectious to man in any area of the inanimate environment. A product 

4408 makes a public health claim if one or more of the following apply: 

4409 (1) A claim is made for control of specific microorganisms that are directly or indirectly 

4410 infectious or pathogenic to man (or both man and animals). Examples of specific microorganisms 

4411 include, but are not limited to:, Mycobacterium tuberculosis, Pseudomonas aeruginosa, 

4412 Escherichia coli (E. coli), human immunodeficiency virus (HIV), Streptococcus, and 

4413 Staphylococcus aureus. Claims for control of microorganisms infectious or pathogenic only to 

4414 animals (such as canine distemper virus or hog cholera virus) are not considered public health 

4415 claims. 

4416 (2) A claim is made for the pesticide product as a sterilant, disinfectant, virucide, 

4417 sanitizer, or tuberculocide against microorganisms that are infectious or pathogenic to man. 

4418 (3) A claim is made for the pesticide product as a fungicide against fungi infectious or 

4419 pathogenic to man, or the product does not clearly state that it is intended for use only against 

4420 nonpublic health fungi. 

4421 (4) A claim is made for the pesticide product as a microbiological water purifier or 

4422 microbial purification system. 

4423 (5) A non-specific claim is made that the pesticide product will beneficially impact or 

4424 affect public health at the site of use or in the environment in which it is applied, and: 

4425 (i) The pesticide product contains one or more ingredients that, under the criteria in 40 

4426 CFR 153.125(a), is an active ingredient with respect to a public health microorganism and there is 

4427 no other functional purpose for the ingredient in the product; or 

4428 (ii) The pesticide product is similar in composition to a registered pesticide product that 

4429 makes antimicrobial public health claims. 
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4430 (b) Nonpublic health claim. An antimicrobial pesticide is considered to 

4431 make a nonpublic health claim if the pesticide product bears a claim to control 

4432 microorganisms of economic or aesthetic significance, where the presence of the 

4433 microorganism would not normally lead to infection or disease in humans. 

4434 Examples of nonpublic health claims include, but are not limited to, algaecides, 

4435 slimicides, preservatives and products for which a pesticidal claim with respect to 

4436 odor sources is made. 

4437 §158.2210 Product chemistry. 

4438 The product chemistry data requirements of subpart D of this part apply to 

4439 antimicrobial products covered by this subpart. 

4440 §158.2220 Product performance. 

4441 (a) General. (1) Product performance requirement for all antimicrobial 

4442 pesticides. Each applicant must ensure through testing that his product is 

4443 efficacious when used in accordance with label directions and commonly 

4444 accepted pest control practices. The Agency may require, on a case-by-case 

4445 basis, submission of product performance data for any pesticide product 

4446 registered or proposed for registration or amendment. 

4447 (2) Product performance data for each product that bears a public health 

4448 claim. Each product that bears a public health claim, as described in 

4449 §158.2204(a), must be supported by product performance data, as listed in the 

4450 table in paragraph (c) of this section. Product performance data must be 

4451 submitted with any application for registration or amended registration. 

4452 (3) Product performance data for each product that bears a nonpublic 

4453 health claim. Each product that bears a nonpublic health claim, as described in 
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4454 §158.2204(b), must be supported by product performance data. Each registrant 

4455 must ensure through testing that his product is efficacious when used in 

4456 accordance with label directions and commonly accepted practices. The Agency 

4457 reserves the right to require, on a case-by-case basis, submission of product 

4458 performance data for any pesticide product registered or proposed for registration 

4459 or amendment. 

4460 (4) Determination of data requirements. Subpart B of this part and 

4461 §158.2201 describe how to use the table in paragraph (c) of this section to 

4462 determine the product performance data requirements for antimicrobial pesticide 

4463 products. 

4464 (b) Key. R = Required; EP = End-use product. 

4465 (c) Table. The following table shows the data requirements 

4466 for antimicrobial product performance. 

4467 Table -- Antimicrobial Product Performance Data Requirements

Guidelin

e 

Number 

Data Requirement All Use Patterns Test Substance

810.210

0 

Sterilants – Efficacy Data 

Recommendations 

R EP 

810.220

0 

Disinfectants for Use on Hard 

Surfaces – Efficacy Data 

Recommendations 

R EP 

810.230

0 

Sanitizers for Use on Hard 

Surfaces – Efficacy Data 

Recommendations 

R EP 

810.240

0 

Disinfectants and Sanitizers for 

Use on Fabrics and Textiles -- 

Efficacy Data Recommendations

R EP 

810.250

0 

Air Sanitizers – Efficacy Data 

Recommendations 

R EP 

810.260

0 

Disinfectants for Use in Water -- 

Efficacy Data Recommendations

R EP 

4468 
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4469 §158.2230 Toxicology. 

4470 (a) General. Subpart B of this part and § 158.2201 describe how to use 

4471 the table in paragraph (g) of this section to determine the toxicology data 

4472 requirements for an antimicrobial pesticide product. Notes that apply to an 

4473 individual test including specific conditions, qualifications, or exceptions are listed 

4474 in paragraph (h) of this section.

4475 (b) Uses. The applicant for registration must first determine whether the 

4476 use is likely to result in pesticide residues in food or water and therefore consult 

4477 the “Food Use” columns of the table in paragraph (g) of this section. Generally, if 

4478 the residues of the antimicrobial result from an application to a surface or 

4479 incorporated into a material that may come into contact with food or feed, and 

4480 residues may be expected to transfer to such food or feed, then the “Indirect Food 

4481 Uses” columns is to be consulted. 

4482 (c) Tiering of data requirements. Applicants for registration of 

4483 antimicrobials may perform tests in a tiered fashion. After the initially required 

4484 tests are conducted, additional testing may be required if results of the initial tests 

4485 trigger the need for additional data. Conditions that trigger the need for additional 

4486 data are given in the test notes in paragraph (h) of this section. 

4487 (d) 200 ppb. The 200 ppb level was originally used by the Food and Drug 

4488 Administration with respect to the concentration of residues in or on food for 

4489 tiering of data requirements for indirect food use biocides. The Agency has also 

4490 adopted this same residue level for determining toxicology data requirements for 

4491 indirect food uses of antimicrobial pesticides. The 200 ppb level is the 

4492 concentration of antimicrobial residues in or on the food item. 
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4493 (e) Use of OSHA standards. If EPA determines that industrial standards, 

4494 such as the workplace standards set by the Occupational Safety and Health 

4495 Administration, provide adequate protection for a particular pesticide or a 

4496 particular use pattern, additional toxicity data may not be required for that 

4497 pesticide or the use pattern. 

4498 (f) Key. R = Required; CR = Conditionally required; NR = Not required; 

4499 MP = Manufacturing-use product; EP = End-use product; TGAI = Technical grade 

4500 of the active ingredient; TEP = Typical end-use product; PAI = Pure active 

4501 ingredient; PAIRA = Pure active ingredient, radiolabeled; Choice = choice of 

4502 several test substances depending on studies required. 
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4503 (g) Table. The following table shows the data requirements for toxicology. The test notes appe4504 of this section. 4505 Table -- Antimicrobial Toxicology Data Requirements 

Guideline Number 

Data Requirement Food Uses Nonfood Uses T

Direct Food Uses 

Indirect Food Uses (> 200 ppb) 

Indirect Food Uses (≤200 ppb) 

Swimming Pools, Aquatic Areas, Wood Preservatives, Metal Working Fluids 

All Other Nonfood Uses M

 Acute Testing 870.1100 Acute oral toxicity – rat R R R R R M

TG

870.1200 Acute dermal toxicity R R R R R M

TG

870.1300 Acute inhalation toxicity 

- rat 

R R R R R M

TG

870.2400 Primary eye irritation - 

rabbit 

R R R R R M

TG

870.2500 Primary dermal irritation R R R R R M

TG

870.2600 Dermal sensitization R R R R R M

TG

870.6200 Acute neurotoxicity - rat R R CR R CR TG Subchronic Testing 870.3100 90-Day oral toxicity - 

rodent 

R R R R CR TG

870.3150 90-Day oral toxicity - 

nonrodent 

R R CR R CR TG

870.3200 21/28-Day dermal 

toxicity 

CR CR CR CR CR TG
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870.3250 90-Day dermal toxicity CR CR CR CR CR TG

870.3465 90-Day inhalation - 

toxicity - rat 

CR CR CR CR CR TG

870.6200 90-Day neurotoxicity - 

rat 

R R CR R CR TG

 Chronic Testing 870.4100 Chronic oral toxicity - 

rodent 

R R CR R CR TG

870.4200 Carcinogenicity – two 

rodent species – rat and mouse preferred 

R R CR R CR TG

 Developmental Toxicity and Reproduction 870.3700 Prenatal developmental 

toxicity - rat and rabbit preferred 

R R R R R TG

870.3800 Reproduction and 

fertility effects 

R R R R R TG

870.6300 Developmental 

neurotoxicity 

CR CR CR CR CR TG

 Mutagenicity 870.5100 Reverse mutation assay R R R R R TG870.5300 870.5375 

In vitro mammalian gene mutation 

R R R R R TG

870.5385 870.5395 

In vivo cytogenetics R R R R R TG

 Special Testing 870.7485 Metabolism and 

pharmacokinetics 

R R CR R CR PA

PA

870.7200 Companion animal 

safety 

CR CR CR CR CR N
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870.7600 Dermal penetration CR CR CR CR CR C

e 

870.7800 Immunotoxicity R R R R R TG

4506 
4507 

4508 

4509 (h) Test notes. The following test notes apply to the data requirements in 

4510 the table to paragraph (g) of this section: 

4511 1. Not required if test material is a gas or highly volatile liquid. 

4512 2. The six end-use product (EP) acute toxicity studies are required using the product as 

4513 formulated for sale and distribution. In addition, if the EP label has directions for diluting the 

4514 product, then, the applicant may also need to conduct certain of the acute toxicity studies using 

4515 the highest concentration labeled for dilution (i.e. the least diluted product). The end-use dilution 

4516 testing is in addition to the testing conducted on the EP. 

4517 3. Not required if test material is corrosive to skin or has pH less than 2 or greater than 

4518 11.5. 

4519 4. Data are required when the product consists of, or under conditions of use will result 

4520 in, a respirable material (e.g., gas, vapor, aerosol or particulates). 

4521 5. Data are required if repeated dermal exposure is likely to occur under conditions of 

4522 use. 

4523 6. For indirect food uses ≤ 200 ppb, and all other nonfood uses, data are required if the 

4524 neurotoxicity screen in the 90-day oral rodent study or other data indicate neurotoxicity. 

4525 7. The 90-day dermal toxicity study and/or 90-day inhalation toxicity study are required if 

4526 the Agency determines that dermal and/or inhalation exposure is the primary route of exposure. 

4527 8. All 90-day subchronic studies in the rodent can be designed to simultaneously fulfill 

4528 the requirements of the 90-day neurotoxicity and/or immunotoxicity studies by adding separate 

4529 groups of animals for testing of neurotoxicity and/or immunotoxicity parameters. 

4530 9. The 90-day study is required in the rodent for hazard characterization (possibly 

4531 endpoint selection) and dose-setting for the chronic/carcinogenicity study. It is not required in the 

4532 mouse, but the Agency would encourage the applicant to conduct a 90-day range finding study 

4533 for the purposes of dose selection for the mouse carcinogenicity study to achieve adequate 

4534 dosing and an acceptable study. 

4535 10. A 1-year non-rodent study (i.e., 1-year dog study) may be required if the Agency 

4536 finds that a pesticide chemical is highly bioaccumulative and slowly eliminated. EPA may also 

4537 require the appropriate metabolism and pharmacokinetic studies to evaluate more precisely 

4538 bioavailability, half life, and steady state to determine if a longer duration dog toxicity study is 

4539 needed. 

4540 11. Although the subchronic toxicity testing guidelines include measurement of 

4541 neurological endpoints, such screens do not meet the requirement of the 90-day neurotoxicity 

4542 study. For nonfood uses, if the 90-day study does not include a neurotoxicity screen, then the 

4543 acute neurotoxicity study will be required. 

4544 12. Data are required if the intended use of the antimicrobial pesticide product is 

4545 expected to result in repeated, dermal human exposure to the product, data from a subchronic 

4546 90-day dermal toxicity study are not available, and the 90-day dermal toxicity study has not been 

4547 triggered. 

4548 13. EP testing is required if the product or any component of the product may increase 

4549 dermal absorption of the active ingredient(s) or increases its toxic or pharmacologic effects, as 

4550 determined by testing using the TGAI or based on available information about the toxic effects of 

4551 the product or its components. 

4552 14. Data are required if the active ingredient in the product is known or expected to be 

4553 metabolized differently by the dermal route of exposure than by the oral route, and a metabolite of 

4554 the active ingredient is the toxic moiety. 

4555 15. A 90-day oral toxicity test is not required for heating, ventilation, air conditioning, and 

4556 refrigeration systems (collectively referred to as HVAC&R). Instead two 90-day toxicity tests, one 

4557 by the dermal route and one by the inhalation route are required. 

4558 16. Data are required if there is the likelihood of significant repeated inhalation exposure 

4559 to the pesticide as a gas, vapor, or aerosol. 
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201

4560 17. Based on estimates of the magnitude and duration of human exposure, studies of 

4561 shorter duration, e.g., 21- or 28-days, may be sufficient to satisfy this requirement. The prime 

4562 consideration in determining the appropriateness of a shorter duration study is the likely period of 

4563 time for which humans will be exposed. 

4564 18. Based on the positive results of the acute or 90-day neurotoxicity studies, or on other 

4565 data indicating neurotoxicity, a chronic neurotoxicity study (i.e. a chronic study with additional 

4566 neurotoxicity evaluations) may be required to provide information about potential neurotoxic 

4567 effects from long-term exposures. 

4568 19. Studies which are designed to simultaneously fulfill the requirements of both the 

4569 chronic oral and carcinogenicity studies (i.e., a combined study) may be conducted. 

4570 20. For indirect food uses ≤ 200 ppb, and all other nonfood uses, data are required if 

4571 either of the following criteria are met: 

4572 i. The use of the pesticide is likely to result in repeated human exposure over a 

4573 considerable portion of the human lifespan; or 

4574 ii. The use requires that a tolerance, tolerance exemption, or food additive regulation or 

4575 clearance be established. 

4576 21. For indirect food uses ≤ 200 ppb, and all other nonfood uses, data are required if any 

4577 of the following criteria, are met: 

4578 i. The use of the pesticide is likely to result in significant human exposure over a 

4579 considerable portion of the human life span which is significant in terms of frequency, time, 

4580 duration, and/or magnitude of exposure. 

4581 ii. The use requires that a tolerance, tolerance exemption, or food additive regulation or 

4582 clearance be established. 

4583 iii. The active ingredient, metabolite, degradate, or impurity: 

4584 A. Is structurally related to a recognized carcinogen; 

4585 B. Causes mutagenic effects as demonstrated by in vitro or in vivo testing; or 

4586 C. Produces a morphologic effect in any organ (e.g., hyperplasia, metaplasia) in 

4587 subchronic studies that may lead to a neoplastic change. 

4588 22. If the requirement for a carcinogenicity study in any species is modified or waived for 

4589 any reason, then a subchronic 90-day oral study in the same species may be required. 

4590 23. Testing in two species is required for all uses. 

4591 24. The oral route, by oral intubation, is preferred, unless the chemical or physical 

4592 properties of the test substance, or the pattern of human exposure, suggest a more appropriate 

4593 route of exposure. 

4594 25. Additional testing by other routes of exposure may be required if the pesticide is 

4595 determined to be a prenatal developmental toxicant after oral dosing. 

4596 26. The developmental toxicity study in rodents may be combined with the two4597 generation reproduction study in rodents by using a second mating of the parental animals in 

4598 either generation. Protocols must be approved by the Agency prior to the initiation of the study. 

4599 27. A two-generation reproduction study is required. 

4600 28. An information-based approach to testing is preferred, which utilizes the best 

4601 available knowledge on the chemical (hazard, pharmacokinetic, or mechanistic data) to determine 

4602 whether a standard guideline study, an enhanced guideline study, or an alternative study should 

4603 be conducted to assess potential hazard to the developing animal. Applicants must submit any 

4604 alternative proposed testing protocols and supporting scientific rationale to the Agency. Protocols 

4605 must be approved by the Agency prior to the initiation of the study. 

4606 29. The use of a combined two-generation reproduction/developmental neurotoxicity 

4607 study that utilizes the two-generation reproduction study in rodents as a basic protocol for the 

4608 addition of other endpoints or functional assessments in the immature animal is encouraged. 

4609 30. A DNT study is required using a weight-of-evidence approach when: 

4610 i. The pesticide causes treatment-related neurological effects in adult animal studies (i.e, 

4611 clinical signs of neurotoxicity, neuropathology, functional or behavioral effects). 

4612 ii. The pesticide causes treatment-related neurological effects in developing animals, 

4613 following pre- or postnatal exposure (i.e., nervous system malformations or neuropathy, brain 

4614 weight changes in offspring, functional or behavioral changes in the offspring). 
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202

4615 iii. The pesticide elicits a causative association between exposures and adverse 

4616 neurological effects in human epidemiological studies. 

4617 iv. The pesticide evokes a mechanism that is associated with adverse effects on the 

4618 development of the nervous system (i.e., structure-activity-relationship (SAR) to known 

4619 neurotoxicants, altered neuroreceptor or neurotransmitter responses). 

4620 31. To facilitate the weight-of-evidence determination for the pesticide’s mutagenicity, 

4621 the Agency requires submission of other mutagenicity test results, besides those specifically 

4622 listed in this table, that may have been performed. A reference list of all studies and papers 

4623 known to the applicant concerning the mutagenicity of the test chemical must be submitted with 

4624 the required studies. 

4625 32. Due to the nature of antimicrobials, if testing with bacterial strains has not been 

4626 conducted, then testing using a mammalian cell assay such as the mouse lymphoma TK +/- 

4627 assay is preferred. If reverse mutation assay testing with bacterial strains has already been 

4628 conducted, and the testing was conducted at levels that did not cause toxicity to the bacterial 

4629 strains tested, then the applicant may submit the study to fulfill this data requirement. 

4630 33. For the in vitro mammalian gene mutation study, there is a choice of assays using 

4631 either mouse lymphoma L5178Y cell thymidine kinase (tk) gene locus, maximizing assay 

4632 conditions for small colony expression and detection; Chinese hamster ovary (CHO) or Chinese 

4633 hamster lung fibroblast (v79) cells, hypoxanthine-guanine phosphoribosyl transferase (hgprt) 

4634 gene locus, accompanied by an appropriate in vitro test for clastogenicity; or CHO cells strains 

4635 AS52, xanthine-guanine phosphoribosyl transferase (xprt) gene locus. 

4636 34. There is a choice of assays, but the micronucleus rodent bone marrow assay is 

4637 preferred; the rodent bone marrow assays using metaphase analysis (aberrations) are 

4638 acceptable. 

4639 35. Data are required when chronic toxicity or carcinogenicity studies are also required. 

4640 36. Data is required if the product label directs that it be applied to domestic animals, 

4641 such as cats, dogs, cattle, pigs, and horses. 4642 37. In the absence of dermal absorption data or a repeated dose dermal toxicity study, 

4643 the assumption of 100% dermal absorption would be used in a risk assessment to determine if a 

4644 dermal penetration study is required, and to identify the doses and duration of exposure for which 

4645 dermal absorption is to be quantified. 

4646 38. Required for nonfood uses, if oral exposure could occur. 

4647 39. Data may be required if significant adverse effects are seen in 

4648 available toxicology studies and these effects can be further elucidated by 

4649 metabolism and pharmacokinetics studies. 

4650 § 158.2240 Nontarget organisms. 

4651 (a) General. Subpart B of this part and § 158.2201 describe how to use 

4652 the table in paragraph (c) of this section to determine the terrestrial and aquatic 

4653 nontarget organisms data requirements for a particular antimicrobial pesticide 

4654 product. Notes that apply to an individual test including specific conditions, 

4655 qualifications, or exceptions are listed in paragraph (d) of this section. 

4656 (1) Terrestrial and aquatic nontarget organism data are required to 

4657 support the registration of most end-use and manufacturing-use antimicrobial 

4658 products. 
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203

4659 (2) Data are generally not required to support end-use products of a gas, 

4660 highly volatile liquid, highly reactive solid, or a highly corrosive material. 

4661 (3) Data on transformation/degradation products or leachate residues of 

4662 the parent compound are also required to support registration, if the 

4663 transformation/degradation/leachate products meet one of the following criteria: 

4664 (i) More toxic, persistent, or bioaccumulative than the parent; 

4665 (ii) Have been shown to cause adverse effects in mammalian or aquatic 

4666 reproductive studies; or 

4667 (iii) The moiety of concern (i.e., functional group in the parent chemical 

4668 molecule that imparts adverse effects) remains intact. 

4669 (4) If an antimicrobial may be applied to a field crop, horticultural crop, or 

4670 turf, then the data requirements in §158.630 apply. 

4671 (5) For the purpose of determining data requirements, the All Other use 

4672 patterns category includes the following use patterns: 

4673 (i) Agricultural premises and equipment. 

4674 (ii) Food-handling/storage establishments, premises, and equipment. 

4675 (iii) Commercial, institutional and industrial premises and equipment. 

4676 (iv) Residential and public access premises. 

4677 (v) Medical premises and equipment. 

4678 (vi) Human drinking water systems. 

4679 (vii) Materials preservatives. 

4680 (viii) Swimming pools. 
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204

4681 (b) Key. MP = Manufacturing use product; EP = End-use product; R = 

4682 Required; CR = Conditionally required; NR = Not required; TGAI = Technical 

4683 grade of the active ingredient; TEP = Typical end-use product; PAIRA = Pure 

4684 active ingredient radiolabeled; a.i. = active ingredient. 

4685 
4686 (c) Table. The following table shows the data requirements for nontarget organisms. Th

4687 in paragraph (d) of this section. 

4688 Table -- Antimicrobial Nontarget Organism Data Requirements 

Guideline Number 

Data Requirement 

Use Pattern 

Industrial Processes and Water Systems 

Antifoulant Coatings and Paints 

Wood Preservatives 

Aquatic Areas 

All Other Use Patterns Category 

Tier One Testing 850.2100 Acute avian oral 

toxicity 

R R R R R 

850.1010 Acute 

freshwater invertebrates toxicity 

R R R R R 

850.1075 Acute 

freshwater fish toxicity 

R R R R R 

Higher Tier Testing Avian Testing 850.2200 Avian dietary 

toxicity 

CR CR CR CR CR 

850.2300 Avian 

reproduction 

CR CR CR CR CR 

Aquatic Organisms Testing 
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206

Guideline Number 

Data Requirement 

Use Pattern 

Industrial Processes and Water Systems 

Antifoulant Coatings and Paints 

Wood Preservatives 

Aquatic Areas 

All Other Use Patterns Category 

850.1010 Acute 

freshwater invertebrates toxicity 

CR CR CR CR CR 

850.1075 Acute 

freshwater fish toxicity 

CR CR CR CR CR 

850.1025 850.1035 850.1045 850.1055 850.1075 

Acute estuarine and marine organisms toxicity 

CR R CR CR CR 

Acute estuarine and marine organisms toxicity 

CR CR CR CR CR 

850.1400 Fish early-life 

stage 

R R R R R 

850.1300 850.1350 

Aquatic invertebrate lifecycle 

R R R R R 

850.1500 Fish life-cycle CR CR CR CR CR 850.1710 Aquatic CR CR CR CR CR 
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Guideline Number 

Data Requirement 

Use Pattern 

Industrial Processes and Water Systems 

Antifoulant Coatings and Paints 

Wood Preservatives 

Aquatic Areas 

All Other Use Patterns Category 

850.1730 850.1850 

organisms, bioavailability, biomagnification, toxicity tests 

850.1950 Simulated or 

actual field testing for aquatic organisms 

CR CR CR CR CR 

Sediment Testing 850.1735 Whole 

sediment; acute freshwater invertebrates 

CR CR CR CR CR 

850.1740 Whole 

sediment; acute marine invertebrates 

CR CR CR CR CR 

None Whole 

sediment; chronic invertebrates 

CR CR CR CR CR 
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208

Guideline Number 

Data Requirement 

Use Pattern 

Industrial Processes and Water Systems 

Antifoulant Coatings and Paints 

Wood Preservatives 

Aquatic Areas 

All Other Use Patterns Category 

fresh-water and marine 

Insect Pollinator Testing 850.3020 Honeybee acute 

contact 

NR NR R NR CR 

850.3030 Toxicity of 

residues to honeybees 

NR NR R NR CR 

4689 
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209

4690 

4691 (d) Test notes. The following test notes apply to the data requirements in 

4692 the table to paragraph (c) of this section: 

4693 1. For industrial processes and water systems, antifoulant paints and coatings, wood 

4694 preservatives, and aquatic areas, data are required for two avian species: one waterfowl species 

4695 and one upland game bird species. For the all other use patterns category (as specified in § 

4696 158.2240(a)(5)), data are required for one avian species. 

4697 2. Data are required on one freshwater aquatic invertebrate species. 

4698 3. For the industrial processes and water systems, antifoulant paints and coatings, wood 

4699 preservatives, and aquatic areas, data are required on two species of fish, one coldwater species 

4700 and one warmwater species. For the all other” use patterns category (as specified in § 

4701 158.2240(a)(5)), data are required on one species of fish, either one coldwater species or a 

4702 warmwater species. Testing on a second species is required if the active ingredient or principal 

transformation products are stable in the environment and the LC50 4703 in the first species is greater 

4704 than 1 ppm or 1 mg/L. 

4705 4. Data are required on one avian species, either one waterfowl species or one upland 

4706 game bird species, if the avian acute oral LD50 ( TGAI testing) is less than or equal to 100 mg. 

4707 a.i./kg and a.i. residues or its principal transformation products are likely to occur in avian feed 

4708 items. Data on the second species are required if the avian dietary LC50 in the first species tested 

4709 is less than or equal to 500 ppm a.i. in the diet. 

4710 5. If TEP testing cannot be conducted due to the physical characteristics of the test 

4711 substance (for example, a paint), then the applicant should request a waiver. 

4712 6. Data are required if one or more of the following criteria are met: 

4713 i. Birds may be subjected to repeated or continued exposure to the pesticide or any of its 

4714 transformation products, especially preceding or during the breeding season. 

4715 ii. The pesticide or any of its major metabolites or degradation products are stable in the 

4716 environment to the extent that a potentially toxic amount may persist in avian feed. 

4717 iii. The pesticide or any of its major metabolites or degradation products are stored or 

4718 accumulated in plant or animal tissues, as indicated by the octanol/water partition coefficient (Kow

4719 is greater than or equal to 1,000), accumulation studies, metabolic release and retention studies, 

4720 or as indicated by structural similarity to known bioaccumulative chemicals. 

4721 iv. Any other information, such as that derived from mammalian reproduction studies, 

4722 indicates that reproduction in terrestrial vertebrates may be adversely affected by the anticipated 

4723 use of the pesticide product. 

4724 7. TEP testing is required for any product which meets one or more of the following 

4725 conditions: 

4726 i. When based on deterministic modeling results: If the Estimated Environmental 

4727 Concentration (EEC) in the aquatic environment is equal to or greater than one-half the LC50/EC50

4728 of the TGAI. 

 ii. When based on probabilistic modeling results: If the estimated 10th 4729 percentile 7Q10 

4730 Surface Water Concentration exceeds the acute concentration of concern (i.e., one-half the 

4731 LC50/EC50) for 4 or more days. 

4732 iii. If an ingredient in the end-use product other than the active ingredient is expected to 

4733 enhance the toxicity of the active ingredient or to cause toxicity to aquatic organisms. 

4734 iv. The end-use antimicrobial product will be applied directly into an aquatic environment. 

4735 8. Data are required on one estuarine/marine mollusk, one other estuarine/marine 

4736 invertebrate, and one estuarine/marine fish species. 

4737 9. For the all other use patterns category (as specified in § 158.2240(a)(5)), industrial 

4738 processes and water systems, wood preservatives, and aquatic areas, data are required if the 

4739 pesticide residues from the parent compound and/or transformation products are likely to enter 

4740 the estuarine/marine environment. 

4741 10. Testing must be conducted with the most sensitive organism (either freshwater or 

4742 estuarine/marine vertebrates, or freshwater or estuarine/marine invertebrates), as determined 
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210

4743 from the results of the acute toxicity tests (acute EC50 freshwater invertebrates; acute LC50/EC50

4744 estuarine and marine organisms; acute freshwater fish LC50). 

4745 11. Data are required on estuarine/marine species if the product is intended for direct 

4746 application to the estuarine or marine environment, or the product is expected to enter this 

4747 environment in significant concentrations because of its expected use or mobility patterns. 

4748 12. Data are required on freshwater species if the end-use product is intended to be 

4749 applied directly to water, or is expected to be transported to water from the intended use site, and 

4750 when one or more of the following conditions apply: 

4751 i. When based on deterministic modeling results: If the Estimated Environmental 

4752 Concentration (EEC) in water is equal to or greater than 0.1 of the no-observed-adverse-effect 

4753 concentration or no-observed-adverse-effect level (NOAEC/NOAEL) in the fish early-life stage or 

4754 invertebrate life cycle tests. 

 ii. When based on probabilistic modeling results: If the estimated 10th 4755 percentile 7Q10 

4756 Surface Water Concentration based on probabilistic modeling exceeds for 20 days or more the 

4757 chronic concentration of concern (i.e., one-tenth the NOAEC or NOAEL) determined in the fish 

4758 early-life stage or invertebrate life cycle tests. 

4759 iii. If studies of other organisms indicate that the reproductive physiology of fish may be 

4760 affected. 

4761 13. Not required when: 

4762 i. The octanol/water partition coefficients of the pesticide and its major degradates are 

4763 less than 1,000; 

4764 ii. There are no potential exposures to fish and other nontarget aquatic organisms; or 

4765 iii. The hydrolytic half-life is less than 5 days at pH 5, 7, and 9. 

4766 14. Environmental chemistry methods used to generate data associated with this study 

4767 must include results of a successful confirmatory method trial by an independent laboratory. Test 

4768 standards and procedures for independent laboratory validation are available as addenda to the 

4769 guideline for this test requirement. 

4770 15. Protocols must be approved by the Agency prior to the initiation of the study. 

4771 16. Data are required if the intended use pattern, and the physical/chemical properties 

4772 and environmental fate characteristics of the antimicrobial indicate significant potential exposure, 

4773 and, based on the results of the acute and chronic aquatic organism testing, significant 

4774 impairment of nontarget aquatic organisms could result. 

4775 17. Data are required if the half-life of the pesticide in the sediment is equal to or less 

4776 than 10 days in either the aerobic soil or aquatic metabolism studies, and if one or more of the 

4777 following conditions are met: 

4778 i. The soil partition coefficient (Kd) is equal to or greater than 50 L/kg. 

4779 ii. The log Kow is equal to or greater than 3. 

4780 iii. The Koc is equal to or greater than 1,000. 

4781 18. Data are required if the EEC in sediment is greater than 0.1 of the acute LC50/EC50 

4782 values and if one or more of the following conditions are met: 

4783 i. The soil partition coefficient (Kd) is equal to or greater than 50 L/kg. 

4784 ii. The log Kow is equal to or greater than 3. 

4785 iii. The Koc is equal to or greater than 1,000. 

4786 19. Sediment testing with estuarine/marine test species is required if the product is 

4787 intended for direct application to the estuarine or marine environment or the product is expected 

4788 to enter this environment in significant concentrations either by runoff or erosion, because of its 

4789 expected use or mobility pattern. 

4790 20. For the all other use patterns category (as specified in § 158.2240(a)(5)), data are 

4791 required only for beehive applications when the beehive (empty or occupied) may be treated. 

4792 21. A study similar to “Honey Bee Toxicity of Residues on Foliage” is required using 

4793 treated wood instead of the foliage. Protocols must be approved by the Agency prior to the 

4794 initiation of the study. 

4795 §158.2250 Nontarget plant protection. 
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211

4796 (a) Subpart B of this part and § 158.2201 describe how to use the table in 

4797 paragraph (f) of this section to determine the nontarget plant protection data 

4798 requirements for a particular antimicrobial pesticide product. Notes that apply to 

4799 an individual test including specific conditions, qualifications, or exceptions are 

4800 listed in paragraph (g) of this section. 

4801 (b) Data on transformation/degradation products or leachate residues of 

4802 the parent compound are also required to support registration, if the 

4803 transformation/degradation/leachate products meet one of the following criteria: 

4804 (i) More toxic, persistent, or bioaccumulative than the parent; 

4805 (ii) Have been shown to cause adverse effects in mammalian or aquatic 

4806 reproductive studies; or 

4807 (iii) The moiety of concern (i.e., functional group in the parent chemical 

4808 molecule that imparts adverse effects) remains intact. 

4809 (c) For the purpose of determining data requirements, the All Other use 

4810 patterns category includes the following use patterns: 

4811 (i) Agricultural premises and equipment. 

4812 (ii) Food-handling/storage establishments, premises, and equipment. 

4813 (iii) Commercial, institutional and industrial premises and equipment. 

4814 (iv) Residential and public access premises. 

4815 (v) Medical premises and equipment. 

4816 (vi) Human drinking water systems. 

4817 (vii) Materials preservatives. 

4818 (viii) Swimming pools. 
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212

4819 (d) If an antimicrobial may be applied to a field crop, horticultural crop, or 

4820 turf, then the data requirements in 40 CFR 158.660 apply. 

4821 (e) Key. MP = Manufacturing use product; EP = End-use product; R = 

4822 Required; CR = Conditionally required; NR = Not required; TGAI = Technical 

4823 grade of the active ingredient; TEP = Typical end-use product. 
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213

4824 (f) Table. The following table shows the data requirements for nontarget plant protection. The t4825 paragraph (g) of this section. 

4826 Table -- Nontarget Plant Protection Data Requirements 

Guideline Number 

Data Requirement 

Use Pattern 

Industrial Processes and Water System 

Antifoulant Coatings and Paints 

Wood Preservatives 

Aquatic Areas 

All Other Use Patterns Category 

850.4225 Seedling 

emergence, Tier II – dose response 

CR CR CR CR CR 

850.4250 Vegetative vigor 

, Tier II – dose response 

CR NR CR CR CR 

850.4400 Aquatic plant 

growth (aquatic vascular plant) Tier II – dose response 

R R R R CR 

850.5400 Aquatic plant 

growth (algal) Tier II (dose response) 

R R R R R 
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214

Guideline Number 

Data Requirement 

Use Pattern 

Industrial Processes and Water System 

Antifoulant Coatings and Paints 

Wood Preservatives 

Aquatic Areas 

All Other Use Patterns Category 

850.4300 Terrestrial field CR CR CR CR CR 850.4450 Aquatic field CR CR CR CR CR 

4827 
4828 (g) Test notes. The following test notes apply to the data requirements in 

4829 the table to paragraph (f) of this section: 

4830 1. Data on only one plant species (rice, Oryza sativa) are required. 

4831 2. Data are required if the risk quotient from any aquatic plant growth Tier II study 

4832 exceeds a level of concern for aquatic plants. 

4833 3. Not required when: 

4834 i. There are no potential exposures to plants; 

4835 ii. The hydrolytic half-life is less than 5 days at pH 5, 7, and 9; or 

4836 iii. The results of a biodegradation study indicate that the active ingredient or principal 

4837 degradation products are not biodegradable in 28 days, i.e. the biodegradation curve has not 

4838 reached a plateau for at least three determinations within the 28 days. 

4839 4. For TEP testing, data are required for the applicant’s end-use product if an ingredient 

4840 in the end-use product, other than the active ingredient, is expected to enhance the toxicity of the 

4841 active ingredient. 

4842 5. One Tier II (dose response) study, conducted with Selenastrum capricornutum, is 

4843 required for the all other use patterns category (as specified in § 158.2250(c)). If the results of 

4844 this study exhibit detrimental effects (EC50 less than 1.0 ppm or mg/L), then additional Tier II 

4845 (dose response) studies are required on three species (Anabaena flos-aquae, Navicula 

4846 pelliculosa, and Skeletonema costatum).

4847 6. For industrial processes and water systems, antifoulant coatings and paints, wood 

4848 preservatives, and aquatic areas, Tier II (dose response) studies are required on four species 

4849 (Anabaena flos-aquae, Navicula pelliculosa, Skeletonema costatum, and Selenastrum 

4850 capricornutum). 

4851 7. Environmental chemistry methods used to generate data must include the results of a 

4852 successful confirmatory method trial by an independent laboratory. 

4853 8. Tests are required on a case-by-case basis based on the results of lower tier plant 

4854 protection studies, adverse incident reports, intended use pattern, and environmental fate 

4855 characteristics that indicate potential exposure. 

4856 9. Protocols must be approved by the Agency prior to the initiation of the study. 

4857 10. For the all other use patterns category (as specified in § 158.2250(c)), data are 

4858 required if the aquatic (algal) plant growth Tier II study demonstrates detrimental effects at less 

4859 than 1.0 ppm or mg/L.

4860 §158.2260 Applicator exposure. 

4861 (a) General. Subpart B of this part and § 158.2201 describe how to use 

4862 the table in paragraph (d) of this section to determine the applicator exposure 

4863 data requirements for antimicrobial pesticide products. Notes that apply to an 

4864 individual test including specific conditions, qualifications, or exceptions are listed 

4865 in paragraph (e) of this section. 

4866 (1) The Agency may accept surrogate exposure data estimations and/or 

4867 modeling estimations from other sources to satisfy exposure data requirements. 

4868 The surrogate data must meet the basic quality assurance, quality control, good 
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216

4869 laboratory practice, and other scientific requirements set by EPA. To be 

4870 acceptable, the Agency must find that the surrogate exposure data estimations 

4871 have adequate information to address the applicable exposure data requirements 

4872 and contain adequate monitoring events of acceptable quality. The data must 

4873 reflect the specific use prescribed on the label and the activity of concern, 

4874 including formulation type, application methods and rates, type of activity, and 

4875 other pertinent information. 

4876 (2) Occupational uses include not only handlers, mixers, loaders, and 

4877 applicators, but also commercial applications to residential sites. Residential 

4878 uses are limited to non-occupational, i.e., non-professional, antimicrobial 

4879 applications. Both occupational and residential applicator data may be required 

4880 for the same product. 

4881 (b) Criteria for testing. Applicator exposure data described in the table to 

4882 paragraph (d) of this section are required based on toxicity and exposure criteria. 

4883 Data are required if at least one of the toxicity criteria in paragraph (b)(1) of this 

4884 section, and at least one of the exposure criteria in paragraph (b)(2) of this 

4885 section are met. 

4886 (1) Toxicity criteria. (i) Evidence of potentially significant adverse effects 

4887 have been observed in any applicable toxicity studies. 

4888 (ii) Scientifically sound epidemiological or poisoning incident data with a 

4889 clear cause-effect relationship indicating that adverse health effects may have 

4890 resulted from exposure to the pesticide. 
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217

4891 (2) Exposure criteria.--(i) Dermal exposure may occur during product 

4892 use. 

4893 (ii) Respiratory exposure may occur during product use. 

4894 (c) Key. R = Required; CR = Conditionally required; TEP = Typical end4895 use product.

4896 (d) Table. The following table shows the data requirements for applicator 

4897 exposure. The test notes appear in paragraph (e) of this section. 

4898 Table -- Antimicrobial Applicator Exposure Data Requirements 

Guidelin

e 

Number 

Data Requirements Use Sites Test 

Substan

ce 

Test 

Note No.

Occupational Residential

875.110

0 

875.120

0 

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

875.130

0 

875.140

0 

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

875.150

0 

Biological monitoring CR CR TEP 1, 2, 3 

875.160

0 

Data reporting and 

calculations 

R R TEP 5 

875.170

0 

Product use information R R TEP -- 

4899 

4900 (e) Test notes. The following test notes apply to the data requirements in 

4901 the table to paragraph (d) of this section: 

4902 1. Prior to initiation of the study, protocols involving intentional exposure of human 

4903 subjects must be submitted for review by EPA and then the Human Studies Review Board 

4904 (HSRB) according to 40 CFR 26.1125. Examples of proposed human study research can be 

4905 found in various reviews provided by the Human Studies Review Board 

4906 (http://www.epa.gov/osa/hsrb/index.htm). 

4907 2. Biological monitoring data may be submitted in addition to, or in lieu of, dermal and 

4908 inhalation passive dosimetry exposure data, provided the human pharmacokinetics of the 

4909 pesticide or metabolite/analog compounds (i.e., whichever method is selected as an indicator of 

4910 body burden or internal dose) allow for the back calculation to the total internal dose. 
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218

4911 3. For products with both indoor and outdoor uses, and similar conditions of use, data 

4912 are generally required for the indoor applications only. However, data for outdoor uses are 

4913 required if the Agency expects outdoor uses to result in greater exposure than indoor uses (e.g., 

4914 higher use rates and application frequency, or longer exposure duration, or application 

4915 methods/equipment create potential for increased dermal or inhalation exposure in outdoor 

4916 versus indoor use sites). In certain cases, when a pesticide may be used both indoors and 

4917 outdoors under dissimilar conditions of use, the Agency may require submission of applicator 

4918 exposure data for both use patterns. 

4919 4. EPA will consider waiving this data requirement for antimicrobials applied via closed 

4920 loading systems if the antimicrobial has a low vapor pressure. 

4921 5. Data reporting and calculations are required only if handler exposure data are 

4922 required. 

4923 §158.2270 Post-application exposure. 

4924 (a) General. Subpart B of this part and § 158.2201 describe how to use 

4925 the table in paragraph (d) of this section to determine the post-application 

4926 exposure data requirements for antimicrobial pesticide products. The data 

4927 generated during these studies are used to determine the quantity of pesticide to 

4928 which people may be exposed after application. Notes that apply to an individual 

4929 test, including specific conditions, qualifications, or exceptions to the designated 

4930 test, are listed in paragraph (e) of this section. 

4931 (1) Post-application exposure data are required when certain toxicity 

4932 criteria are met and the human activities associated with the pesticide's use 

4933 pattern can lead to potential adverse exposures. 

4934 (2) The Agency may accept surrogate exposure data estimations and/or 

4935 modeling estimations from other sources to satisfy exposure data requirements. 

4936 The surrogate data must meet the basic quality assurance, quality control, good 

4937 laboratory practice, and other scientific requirements set by EPA. To be 

4938 acceptable, the Agency must find that the surrogate exposure data estimations 

4939 have adequate information to address the applicable exposure data requirements 

4940 and contain adequate monitoring events of acceptable quality. The data must 
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219

4941 reflect the specific use prescribed on the label and the activity of concern, 

4942 including formulation type, application methods and rates, type of activity, and 

4943 other pertinent information. 

4944 (b) Criteria for testing. Post-application exposure data described in the 

4945 table to paragraph (d) of this section are required based on toxicity and exposure 

4946 criteria. Data are required if at least one of the toxicity criteria in paragraph (b)(1) 

4947 of this section, and at least one of the exposure criteria in paragraph (b)(2) of this 

4948 section are met. 

4949 (1) Toxicity criteria.--(i) Evidence of potentially significant adverse effects 

4950 have been observed in any applicable toxicity studies. 

4951 (ii) Scientifically sound epidemiological or poisoning incident data with a 

4952 clear cause-effect relationship indicating that adverse health effects may have 

4953 resulted from exposure to the pesticide. 

4954 (2) Exposure criteria. --(i) Outdoor uses. (A) Occupational human post4955 application or bystander exposure to residues of antimicrobial pesticides could 

4956 occur as the result of, but is not limited to, worker re-entry into treatment sites, 

4957 clean-up and equipment maintenance tasks, handling wood preservative-treated 

4958 wood, or other work-related activity. 

4959 (B) Residential human post-application or bystander exposure to residues 

4960 of antimicrobial pesticides could occur following the application of antimicrobials 

4961 pesticides to outdoor areas and spaces at residential sites, such as, but not 

4962 limited to homes, daycare centers, and other public buildings. 
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220

4963 (ii) Indoor uses. (A) Occupational human post-application or bystander 

4964 exposure to pesticide residues could occur following the application of the 

4965 antimicrobial pesticide to indoor spaces or surfaces. 

4966 (B) Residential human post-application or bystander exposure to 

4967 pesticide residues could occur following the application of the antimicrobial 

4968 pesticide to indoor spaces or surfaces at residential sites, such as, but not limited 

4969 to homes, daycare centers, hospitals, schools, and other public buildings. 

4970 (c) Key. R = Required; CR = Conditionally required; NR = Not required; 

4971 TEP = Typical end-use product. 

4972 (d) Table. The following table shows the data requirements for post4973 application exposure. The test notes appear in paragraph (e) of this section. 

4974 Table -- Antimicrobial Post-Application Exposure Data Requirements. 

Guideline 

Number 

 Data 

Requirement 

Use Sites Test 

Substance 

to Support 

Test Note 

Occupational Residential No. 

875.2200 Soil residue 

dissipation 

CR CR TEP 2, 3 

875.2300 Indoor surface 

residue 

dissipation 

CR R TEP 3, 4, 5, 6 

875.2400 Dermal exposure CR CR TEP 1, 7, 8 

875.2500 Inhalation 

exposure 

CR CR TEP 1,7, 8, 9 

875.2600 Biological 

monitoring 

CR CR TEP 1, 8 

875.2700 Product use 

information 

R R TEP --- 

875.2800 Description of 

human activity 

R R TEP --- 

875.2900 Data reporting 

and calculations 

R R TEP 10 

4975 
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4976 (e) Test notes. The following test notes apply to the data requirements in 

4977 the table to paragraph (d) of this section: 

4978 1. Prior to initiation of the study, protocols involving intentional exposure of human 

4979 subjects must be submitted for review by EPA and then the Human Studies Review Board 

4980 (HSRB) according to 40 CFR 26.1125. Examples of proposed human study research can be 

4981 found in various reviews provided by the Human Studies Review Board (HSRB) 

4982 (http://www.epa.gov/osa/hsrb/index.htm). 

4983 2. For residential wood preservative uses, data may be required if soil has the potential 

4984 to be an important exposure pathway, and soil is in contact with or adjacent to treated wood, 

4985 including but not limited to decks, play sets, and gazebos, 

4986 3. Protocols must be approved by the Agency prior to the initiation of the study. 

4987 4. For wood preservatives, data are required for treated wood surfaces where post4988 application contact with treated wood is anticipated. 

4989 5. For occupational uses, data are required if the pesticide may be applied to or around 

4990 surfaces, and if the human activity data indicate that workers are likely to have post-application 

4991 dermal contact with treated surfaces while participating in typical activities. 

4992 6. Data are required for residential use sites, schools, and daycare institutions. This 

4993 includes but is not limited to the following: Residential and public access premises; material 

4994 preservatives (including those used in residential products, including but not limited to clothing 

4995 and plastic toys) and wood preservatives (when contact with treated wood is likely to occur). 

4996 7. Data are required for occupational and residential uses if the human activity data 

4997 indicate the potential for post-application dermal and/or inhalation exposures while participating in 

4998 typical activities and no acceptable modeling options are available. 

4999 8. Biological monitoring data may be submitted in addition to, or in lieu of, dermal and 

5000 inhalation passive dosimetry exposure data provided the human pharmacokinetics of the 

5001 pesticide or metabolite/analog compounds (i.e., whichever method is selected as an indicator of 

5002 body burden or internal dose) allow for a back-calculation to the total internal dose. 

5003 9. Data are required for occupational and residential uses if there is the potential for 

5004 bystander exposure and the pesticide use could result in respirable and/or inhalable material 

5005 (e.g., gas, vapor, aerosol, or particulates). 

5006 10. Data reporting and calculations are required only if post-application exposure data 

5007 are required. 

5008 §158.2280 Environmental fate. 

5009 (a) General. Subpart B of this part and § 158.2201 describe how to use 

5010 the table in paragraph (c) of this section to determine the environmental fate data 

5011 requirements for antimicrobial pesticide products. Notes that apply to an 

5012 individual test including specific conditions, qualifications, or exceptions are listed 

5013 in paragraph (d) of this section. 

5014 (1) Environmental fate data are required to support the registrations of all 

5015 end-use and manufacturing-use antimicrobial products. 
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222

5016 (2) Data on transformation/degradation products or leachate residues of 

5017 the parent compound are also required to support registration, if the 

5018 transformation/degradation/leachate products meet one of the following criteria: 

5019 (i) More toxic, persistent, or bioaccumulative than the parent; 

5020 (ii) Have been shown to cause adverse effects in mammalian or aquatic 

5021 reproductive studies; or 

5022 (iii) The moiety of concern (i.e., functional group in the parent chemical 

5023 molecule that imparts adverse effects) remains intact. 

5024 (3) For the purpose of determining data requirements, the “All Other” use 

5025 patterns category includes the following use patterns: 

5026 (i) Agricultural premises and equipment. 

5027 (ii) Food-handling/storage establishments, premises, and equipment. 

5028 (iii) Commercial, institutional and industrial premises and equipment. 

5029 (iv) Residential and public access premises. 

5030 (v) Medical premises and equipment. 

5031 (vi) Human drinking water systems. 

5032 (vii) Materials preservatives. 

5033 (viii) Swimming pools.

5034 (b) Key . MP = Manufacturing use product; EP = End-use product; R = 

5035 Required; CR = Conditionally required; NR = Not required; TGAI = Technical 

5036 grade of the active ingredient; TEP = Typical end-use product; PAIRA = Pure 

5037 active ingredient radiolabeled; ROC = residue of concern. 

5038 
5039 (c) Table. The following table shows the data requirements for environmental fate. The test no

5040 paragraph (d) of this section. 5041 Table -- Antimicrobial Environmental Fate Data Requirements 

Guideline Number 

Data Requirement 

Use Pattern Test Sub

Industrial Processes and Water Systems 

Antifoulant Coatings and Paints 

Wood Preservatives 

Aquatic Areas 

All Other Use Patterns Category 

MP 

Degradation Studies – Laboratory 835.2120 

Hydrolysis R R R R R TGAI or 

PAIRA 

835.2240 

Photodegradation in water 

R R R R R TGAI or 

PAIRA 

835.2410 

Photodegradation in soil 

NR NR R NR NR TGAI or 

PAIRA 

Toxicity and Fate in Wastewater Systems 850.6800 OECD 209 

Activated Sludge, Respiration Inhibition Test 

R R R NR R TGAI 

835.1110 

Activated Sludge Sorption Isotherm 

CR CR CR NR CR TGAI 

835.311 Ready CR CR CR NR CR TGAI 
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224

0 Biodegradabilit

y 

835.3220 

Porous Pot Study 

CR CR CR NR CR TGAI 

835.3280 

Simulation Tests to Assess the Biodegradability of Chemicals Discharged in Wastewater 

CR CR CR NR CR TGAI 

835.3240 

Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units 

CR CR CR NR CR TGAI 

Mobility Studies 835.1230 835.1240 

Leaching and adsorption/desorption 

R R R R CR TGAI or 

PAIRA 

Metabolism Studies – Laboratory 835.4100 

Aerobic soil metabolism 

CR NR R CR CR TGAI or 

PAIRA 

835.4200 

Anaerobic soil metabolism 

NR NR R NR CR TGAI or 

PAIRA 

835.430 Aerobic aquatic R R R R CR TGAI or 
*** Deliberative Internal Document – Do NOT Cite, Quote, or Release *** 

225

0 metabolism PAIRA 

835.4400 

Anaerobic aquatic metabolism 

R R R R CR TGAI or 

PAIRA 

Dissipation Studies – Field 835.6200 

Aquatic (sediment) 

CR R CR R CR TEP 

Ground and Surface Water Monitoring None Monitoring of 

representative U.S. waters 

CR CR CR CR CR ROC 

Special Studies None Special 

leaching 

NR R R NR NR TGAI 
226

226

5042 (d) Test notes. The following test notes apply to the data requirements in 

5043 the table in paragraph (c) of this section: 

5044 1. For testing antifoulant paints and coatings, testing is to be performed separately with 

5045 both sterile buffered distilled water and sterile synthetic seawater at pHs 5, 7, and 9. 

5046 2. Not required if: 

5047 (i) The electronic absorption spectra, measured at pHs 5, 7 and 9, of the chemical and 

5048 its hydrolytic products, if any, show no absorption or tailing between 290 and 800 nm, inclusive; 

5049 or 

5050 (ii) The results of the hydrolysis study at all three pHs (5, 7, and 9) demonstrates a half5051 life of less than 30 days. 

5052 3. The results of the activated sludge, respiration inhibition (ASRI) test determine which 

5053 of the following tests are required: Ready biodegradability, porous pot, the biodegradation in 

5054 activated sludge study as described in the “Simulation Tests to Assess the Biodegradability of 

5055 Chemicals Discharged in Wastewater,” or simulation test – aerobic sewage treatment: A. 

5056 activated sludge units. 

5057 (i). If the ASRI test EC50 is equal to or less than 20 mg/L, then the applicant must choose 

5058 either to: 

5059 (A). Conduct the biodegradation in activated sludge study as described in the “Simulation 

5060 Tests to Assess the Biodegradability of Chemicals Discharged in Wastewater”; 

5061 (B). Conduct the porous pot test; or 

5062 (C). Conduct the simulation test – aerobic sewage treatment: A. activated sludge units. 

5063 (ii). If the ASRI test EC50 is greater than 20 mg/L, then the applicant must choose either 

5064 to: 

5065 (A). Conduct a ready biodegradability study; or 

5066 (B). Conduct one of the following studies: The biodegradation in activated sludge study 

5067 as described in the “Simulation Tests to Assess the Biodegradability of Chemicals Discharged in 

5068 Wastewater,” the porous pot test, or the simulation test – aerobic sewage treatment: A. activated 

5069 sludge units. 

5070 4. Pass criteria for the ready biodegradability study are: 70% removal of dissolved 

5071 organic carbon (DOC) and 60% removal of theoretical oxygen demand (ThOD) or theoretical 

5072 carbon dioxide (ThCO2) production for respirometric methods. These pass levels must be 

5073 reached in a 10-day window within the 28-day period of the test. If the antimicrobial passes the 

5074 ready biodegradability study, then no further testing is required. If the antimicrobial fails the ready 

5075 biodegradability study, then the applicant must conduct one of the following studies: The 

5076 biodegradation in activated sludge study as described in the “Simulation Tests to Assess the 

5077 Biodegradability of Chemicals Discharged in Wastewater,” the porous pot test, or the simulation 

5078 test – aerobic sewage treatment: A. activated sludge units. 

5079 5. For the all other use patterns category (as specified in § 158.2280(a)(3)), data are 

5080 required based on a weight-of-evidence evaluation of the results of the hydrolysis, 

5081 photodegradation in water, activated sludge sorption isotherm, biodegradability, and activated 

5082 sludge, respiration inhibition tests. 

5083 6. Adsorption and desorption using a batch equilibrium method is preferred. In some 

5084 cases, as when the antimicrobial pesticide degrades rapidly, soil column leaching with unaged or 

5085 aged columns may be more appropriate to fully characterize the potential mobility of the parent 

5086 compound and major transformation products. 

5087 7. For industrial processes and water systems, aquatic areas, and the all other use 

5088 patterns category (as specified in § 158.2280(a)(3)), data are required based on a weight-of5089 evidence evaluation of the results of the hydrolysis, photodegradation in water, activated sludge 

5090 sorption isotherm, biodegradability, and activated sludge, respiration inhibition tests. 

5091 8. The environmental media (soil, water, hydrosoil, and biota) to be utilized in these 

5092 studies must be collected from areas representative of potential use sites. 

5093 9. For industrial processes and water systems, and aquatic areas, data are required for 

5094 use sites that are intermittently dry. 
227

227

5095 10. For non-metallic antimicrobials, data are not required if the standardized soil profiles 

5096 demonstrate that the antimicrobial is likely to readily degrade either microbially or via redox 

5097 reactions (chemically). 

5098 11. Analytical methods used to generate data associated with this study must include 

5099 results of a successful confirmatory method trial by an independent laboratory. 

5100 12. Protocols must be approved by the Agency prior to the initiation of the study. 

5101 13. For industrial processes and water systems, wood preservatives, and the all other 

5102 use patterns category (as specified in § 158.2280(a)(3)), data are required based on the potential 

5103 for aquatic exposure and if the weight-of-evidence indicates that the active ingredient or principal 

5104 transformation products are likely to have the potential for persistence, mobility, nontarget aquatic 

5105 toxicity, or bioaccumulation. 

5106 14. Data are required if the weight-of-evidence indicates that the active ingredient or 

5107 principal transformation products are likely to occur in nontarget freshwater, estuarine, or marine 

5108 waters such that human or environmental exposures are likely to occur. In making that 

5109 determination, the Agency takes into account other factors such as the toxicity of the chemical(s), 

5110 available monitoring data and the vulnerability of the freshwater, estuarine, or marine water 

5111 resources in the antimicrobial use area. 

5112 15. For wood preservatives, an aquatic leaching study is required. A soil leaching study 

5113 is required if human or environmental exposures are likely to occur from leachates that contain 

5114 the active ingredient or principal transformation products from wood treated with a preservative 

5115 product. Protocols must be approved by the Agency prior to the initiation of the study. 

5116 16. For antifoulant paints and coatings, a leaching study is required. Protocols must be 

5117 approved by the Agency prior to the initiation of the study. 

5118 17. Protocols, which include the residues of concern (such as parent, 

5119 degradate/transformation product, and/or leachate residues) that would be monitored, must be 

5120 approved by the Agency prior to the initiation of the study. 

5121 18. A biodegradation study is not required if the antimicrobial meets one or more of the 

5122 following criteria: 

5123 i. Classified as a metal; 

5124 ii. Relatively volatile, but not hydrophobic; 

5125 iii. Highly reactive. 

5126 19. The Activated Sludge Sorption Isotherm test is not required if the antimicrobial is: 

5127 i. Relatively volatile, but not hydrophobic; 

5128 ii. Highly reactive; or 

5129 iii. The log Kow is less than 3.0. 

5130 20. If the criteria of test note (19) of this paragraph are not met, then the Activated 

5131 Sludge Sorption Isotherm test is required if one or more of the following criteria are met: 

5132 i. The antimicrobial is a metal. 

5133 ii. The log Kow is greater than or equal to 3.0. 

5134 iii. The antimicrobial is positively charged or polycationic. 

5135 iv. The EC50 in the activated sludge, respiration inhibition test is less than or equal to 20 

5136 mg/L. 

5137 v. The EC50 in the activated sludge, respiration inhibition test is greater than 20 mg/L, 

5138 and the antimicrobial fails the ready biodegradability study. 

5139 

5140 § 158.2290 Residue Chemistry 
228

228

5141 (a) General. Subpart B of this part and §158.2201 describe how to use 

5142 the table in paragraph (h) of this section to determine the residue chemistry data 

5143 requirements for antimicrobial pesticide products. Notes that apply to an 

5144 individual test including specific conditions, qualifications, or exceptions are listed 

5145 in paragraph (i) of this section. 

5146 (b) Residue chemistry data are required for: 

5147 (1) Antimicrobial end-use products with uses that may result in residues in 

5148 or on food including, but not limited to: 

5149 (i) Products that require a tolerance, tolerance exemption, or food additive 

5150 regulation or clearance. 

5151 (ii) Products that may be used to treat livestock or poultry drinking water, 

5152 for food egg washing, or for fruit and vegetable rinses. 

5153 (iii) Products that may be applied to a surface or incorporated into a 

5154 material that may contact food or feed. Data are required regardless of whether 

5155 the antimicrobial is applied or impregnated for the purpose of imparting 

5156 antimicrobial protection to external surfaces of the substance or article, or for the 

5157 purpose of protecting the substance or article itself. 

5158 (iv) Products that may be applied to water that have the potential to result 

5159 in residues in potable water, or in water used for livestock and poultry drinking 

5160 water, irrigation of crops, or water containing fish that may be used for human 

5161 food. 
229

229

5162 (v) Wood preservative or antifoulant products intended for treating 

5163 submerged materials that may result in food contact (e.g., lobster pots, fish 

5164 cages on fish farms). 

5165 (2) Each manufacturing-use product bearing directions for formulation into 

5166 an end-use product bearing uses described in paragraph (b)(1) of this section. 

5167 (c) Residue chemistry data are not required under paragraph (b) of this 

5168 section if no adverse effects (no toxicity endpoints) are associated with dietary 

5169 exposure to the active ingredient or if theoretical (high-end) dietary exposure 

5170 estimates combined with the applicable toxicity endpoint result in acute and 

5171 chronic dietary risks that are below the Agency levels of concern. 

5172 (d) For purposes of this section, Magnitude of the Residue Studies 

5173 include the following: Food-handling, migration studies, potable water, fish, 

5174 irrigated crops, meat/milk/poultry/eggs, crop field trails, processed food or feed, 

5175 and anticipated residues. 

5176 (e) If the antimicrobial chemical may be applied to a field crop, then the 

5177 residue chemistry data requirements of §158.1410 apply. 

5178 (f) The following term is defined for the purposes of this section: 

5179 Residue of concern means the parent pesticidal compound and its metabolites, 

5180 degradates, and impurities of toxicological concern. 

5181 (g) Key. R = Required; CR = Conditionally required; NR = Not required; 

5182 TGAI = Technical grade of the active ingredient; TEP = Typical end-use product; 

5183 PAI = Pure active ingredient; PAIRA = Pure active ingredient radiolabeled; ROC 

5184 = Residue of concern.
230

230

5185 (h) Table. The following table shows the data requirements for residue chemistry. The test not5186 paragraph (i) of this section. 

5187 Table -- Antimicrobial Residue Chemistry Data Requirements 

Guideline Number 

Data Requirement Uses Test 

Subs

Agricultural 

Premise 

Indirect 

Food 

Direct Food Aquatic 

Supporting Information 860.1100 Chemical identity R R R R TGAI 860.1200 Directions for use R R R R -- 860.1550 Proposed 

tolerance/tolerance exemption 

R R R R -- 

860.1560 Reasonable 

grounds in support of petition 

R R R R -- 

860.1650 Submittal of 

analytical reference standards 

R R R R PAI/R

Food-Contact Surfaces Or Impregnated Materials 

860.1460 Food-handling CR CR CR CR TEP 
231

231

None 

Nature of residue on surfaces CR CR CR CR 

PAIRTGAI 

None Migration studies CR CR CR CR TEP 860.1340 

Residue analytical method for data collection 

CR CR CR CR ROC 

860.1380 Storage stability R R R R TEP 

ROC 

Higher tiered 

860.1300 

Nature of the residue in plants CR CR CR CR PAIR

860.1300 

Nature of the residue in livestock CR CR CR CR PAIR

860.1340 

Residue analytical methods for tolerance/tolerance exemption enforcement 

CR CR CR CR ROC 

860.1360 Multiresidue 

method testing 

CR CR CR CR ROC 

860.1400 Potable water CR CR CR CR TEP 860.1400 Fish CR CR CR CR TEP 860.1400 Irrigated crops CR CR CR CR TEP 860.1480 Meat/milk/poultry/ 

eggs 

CR CR CR CR TGAI 

ROC 

860.1500 Crop field trials CR CR CR CR TEP 860.1520 Processed food or 

feed 

CR CR CR CR TEP 

None Anticipated CR CR CR CR ROC 
232

232

residues 

5188 5189 5190 
5191 

5192 

5193 

5194 (i) Test notes. The following test notes apply to the data requirements in 

5195 the table to paragraph (h) of this section: 

5196 1. A petition proposing a numerical tolerance or a tolerance exemption is required for 

5197 any food or feed use subject to section 408 of FFDCA if the use is not covered by an existing 

5198 tolerance or tolerance exemption. If the use is subject to FFDCA section 409, the applicant must 

5199 identify to EPA an applicable section 409 food additive regulation or clearance, or submit a copy 

5200 of a petition to FDA requesting a section 409 food additive regulation or clearance for the food or 

5201 feed use. 

5202 2. An analytical reference standard is required for any food or feed use requiring a 

5203 numeric tolerance or exemption. Material safety data sheets as specified by Occupational Safety 

5204 and Health Administration in 29 CFR 1910.1200 must accompany analytical standards. 

5205 3. Data are required if a pesticide may be used in a food-handling establishment unless 

5206 data including, but not limited to, theoretical (high-end) estimates, radiolabeled laboratory data, or 

5207 the nature of the residue on surfaces study show that residues will not occur in food or feed. 

5208 4. If an antimicrobial pesticide may be applied to a food-contact surface or impregnated 

5209 into a food-contact material and if theoretical (high-end) estimates of exposure exceed EPA’s risk 

5210 level of concern, then the nature of the residue on surfaces study is required. Protocols must be 

5211 approved by the Agency prior to the initiation of the study. 

5212 5. Based on the results of the nature of the residue on surfaces study, if residues of 

5213 concern are identified, then the migration study will be required. Protocols must be approved by 

5214 the Agency prior to the initiation of the study. 

5215 6. If a magnitude of the residue study, as specified in §158.2290(d), is required, then a 

5216 residue analytical method suitable for collecting data is also required. The method must be 

5217 capable of determining all residues of concern, to permit calculation of dietary risk or to establish 

5218 a tolerance or tolerance exemption. 

5219 7. If a magnitude of the residue study, as specified in §158.2290(d), is required, then 

5220 storage stability data are also required, unless analytical samples are stored for 30 days or less. 

5221 If, during hazard characterization, a residue has been identified as “of concern” and is known to 

5222 be volatile or labile, then storage stability data are required regardless of sample storage time. 

5223 8. If crop plants or metabolically active raw agricultural commodities of food crops may 

5224 be directly or indirectly exposed to an antimicrobial, plant metabolism studies are required to 

5225 determine the transformation products that may enter the human diet. Such exposure could 

5226 include, but is not limited to: 

5227 i. Treatment of storage or shipping containers, 

5228 ii. Postharvest fruit and vegetable treatment prior to shipping or storage, 

5229 iii. Use of antimicrobial-treated water for irrigation, and 

5230 iv. Any direct food contact use. 

5231 9. If livestock may be exposed to an antimicrobial, then hen and ruminant metabolism 

5232 studies are required to determine the identities of residues of concern that may enter the human 

5233 diet from consumption of livestock commodities. Livestock may be exposed via the oral, dermal, 

5234 or inhalation route following treatment or contamination of sites including, but not limited to, 

5235 livestock premises, feed, and drinking water. Shell eggs and other metabolically active livestock 

5236 products may also be treated. If livestock may be exposed to one or more residues of concern 

5237 differing from those found in animals, then one or more additional livestock metabolism studies 

5238 involving dosing with these residues may be required. 
234

234

5239 10. If there is a numerical tolerance or tolerance exemption level to enforce, then a 

5240 residue analytical method suitable for enforcement purposes is required. The method must be 

5241 supported by an independent laboratory validation. 

5242 11. If there is a numerical tolerance or tolerance exemption level to enforce, then testing 

5243 is required to determine whether the Food and Drug Administration/United States Department of 

5244 Agriculture multiresidue methodology would detect and identify the antimicrobial and its residues 

5245 of concern, as part of programs to monitor pesticides in the U.S. food supply. 

5246 12. Data are required if an antimicrobial may be applied directly to water or if there is the 

5247 potential that the antimicrobial-treated water could be used directly for drinking water purposes by 

5248 humans or animals or that contaminated water could run-off, leach, or be discharged from treated 

5249 sites or materials and make its way into potable water. 

5250 13. Data are required if an antimicrobial may be applied directly to water inhabited by 

5251 fish or that will be inhabited by fish or if contaminated water could run-off, leach, or be discharged 

5252 from treated sites or materials and make its way into bodies of water containing fish that may be 

5253 used for human consumption. 

5254 14. Data are required if an antimicrobial may be applied directly to water used for 

5255 irrigation of food crops or such that contaminated water could run-off, leach, or be discharged 

5256 from treated sites or materials to make its way into water used for irrigation of food crops. 

5257 15. If the antimicrobial may be applied directly to livestock, metabolically-active livestock 

5258 commodities (e.g., eggs), livestock feed or drinking water, or livestock premises, or a livestock 

5259 metabolism study indicates that residues of the antimicrobial may result in livestock commodities, 

5260 studies are required to determine the magnitude of the residues of concern in fat, meat, meat by5261 products, milk, poultry, and eggs that may be consumed by humans. These studies, however, 

5262 may not be required in cases where the livestock metabolism studies indicate that transfer of 

5263 pesticide residues of concern to tissues, milk, and eggs is not expected to occur at the maximum 

5264 expected exposure level for the animals. 

5265 16. If food crops or raw agricultural commodities of food crops may be exposed to an 

5266 antimicrobial, then residue studies are required to determine the magnitude of the residues of 

5267 concern that may enter the human diet. Such exposures include, but are not limited to, 

5268 postharvest fruit and vegetable treatments and application of antimicrobial chemicals to field 

5269 crops, mushroom houses, empty or occupied beehives, or wood used to construct beehives. 

5270 17. Data on the nature and magnitude of residues in processed food or feed are required 

5271 if antimicrobial residues could potentially concentrate on processing. If so, the establishment of a 

5272 separate tolerance higher than that in the raw agricultural commodity may be required. 

5273 18. Data are required when dietary exposure values at the tolerance level or screening5274 level (high-end) result in estimates of dietary or aggregate risk that meet or exceed the Agency’s 

5275 level of concern. These data may include, but are not limited to, washing, cooking, processing, or 

5276 degradation studies as well as market basket surveys for a more realistic residue determination. 

5277 Protocols must be approved by the Agency prior to the initiation of the study. 

5278 

5279 

5280 PART 161—[AMENDED] 

5281 

5282 7. The authority citation for part 161 continues to read as follows: 

5283 Authority: 7 U.S.C. 136 – 136y. 

5284 

5285 Part 161 [Removed] 

5286 

5287 8. Part 161 is removed: