*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 1 of 233 

1 EO12866_RIN_2070-AD30_Part 158W-FRM_2012-11-29.docx

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

3 Draft document submittedas revised during Interagency review. 

4 BILLING CODE 6560–50–P 

5 ENVIRONMENTAL PROTECTION AGENCY 

6 40 CFR Parts 158 and 161

7 [EPA–HQ–OPP–2008–0110; FRL–XXXX–X8886–5]

8 RIN 2070–AD30 

9 Data Requirements for Antimicrobial Pesticides

10 AGENCY: Environmental Protection Agency (EPA). 

11 ACTION: Final rule. 

12 SUMMARY: EPA is revising and updating the data requirements for antimicrobial 

13 pesticide products, which to reflect current scientific and regulatory practices. Besides 

14 providing, and to provide the regulated community with clearer and more transparent 

15 information, about the data needed to support pesticide registration decisions for 

16 antimicrobial products. The updated data requirements also serve to further enhance 

17 EPA’s ability to make regulatory decisions about the human health, and environmental 

18 fate and effects of antimicrobial pesticide products. These revisions are also expected 

19 to help protect human health and the environment by providing an up-to-date scientific 

20 framework for identifying and assessing the risks of antimicrobial pesticides sold or 

21 distributed in the United States.

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

23 Federal Register]. 

24 ADDRESSES: EPA has established aThe docket for this action, identified under docket 

25 identification (ID) number EPA–HQ–OPP–2008–0110. All documents in the docket are 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 2 of 233 

26 listed in the docket index, is available at http://www.regulations.gov. Although listed in 

27 the index, some information is not publicly available, e.g., Confidential Business 

28 Information (CBI) or other information whose disclosure is restricted by statute. Certain 

29 other material, such as copyrighted material, is not placed on the Internet and will be 

30 publicly available only in hard copy form. Publicly available docket materials are 

31 available in the electronic docket at http://www.regulations.gov, or, if only available in 

32 hard copy, at the OPP Regulatory Public Docket in Rm. S–4400, One Potomac Yard 

33 (Souththe Environmental Protection Agency Docket Center (EPA/DC), located in the 

34 EPA West Bldg.), 2777 S. Crystal Dr., Arlington, VA. The Docket Facility., Rm. 3334, 

35 1301 Constitution Ave., NW., Washington, DC 20460-0001. The Public Reading Room

36 is open from 8:30 a.m. to 4:30 p.m., Monday through Friday, excluding legal holidays. 

37 The Docket Facility telephone number for the Public Reading Room is (202) 566-1744, 

38 and the telephone number for the OPP Docket is (703) 305–-5805. Please review the 

39 visitor instructions and additional information about the docket available at 

40 http://www.epa.gov/dockets. 

41 FOR FURTHER INFORMATION CONTACT: Kathryn Boyle, Field and External Affairs 

42 Division (7506P), Office of Pesticide Programs, Environmental Protection Agency, 1200 

43 Pennsylvania Ave., NW., Washington, DC 20460–0001; telephone number: (703) 305-

44 6304; e-mail address: boyle.kathryn@epa.gov, or contact Scott Drewes, same address; 

45 telephone number (703) 347-0107; email address: drewes.scott@epa.gov. 

46 SUPPLEMENTARY INFORMATION: 

47 I. General InformationExecutive Summary

48 A. Does this Action Apply to Me? 

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

50 (NAICS 32532), antifoulants (NAICS 32551), antimicrobial pesticides (NAICS 32561) or 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 3 of 233 

51 wood preservatives (NAICS 32519), importers of such products, or any person or 

52 company who seeks to register an antimicrobial, antifoulant coating, ballast water 

53 treatment, or wood preservative pesticide or to obtain a tolerance for such a pesticide. 

54 The North American Industrial Classification System (NAICS) codes have been 

55 provided to assist you and others in determining whether this action might apply to 

56 certain entities. This listing is not intended to be exhaustive, but rather provides a guide 

57 for readers regarding entities likely to be affected by this action. Other types of entities 

58 not listed above could also be affected. could also be affected. The North American 

59 Industrial Classification System (NAICS) codes have been provided to assist you and 

60 others in determining whether this action might apply to certain entities. If you have any 

61 questions regarding the applicability of this action to a particular entity, please contact 

62 Nader Elkassabany, Chief of the Risk Assessment and Science Support Branch in the 

63 Antimicrobials Division of the Office of Pesticide Programs at (703) 308-8783 or via 

64 email, .

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

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

67 

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

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

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

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

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

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

74 electronically, please go to and select “Test Methods and Guidelines.” 

75 II. Background

76 A.This action is issued under the authority of sections 2, 3, 4, 5, 10, 12, and 25 of 

77 the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), 7 U.S.C. 136 et seq., 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 4 of 233 

78 and section 408 of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 

79 346a. The data required for antimicrobials (e.g., for registration, reregistration or 

80 registration review, experimental use permit (EUP), or tolerance/tolerance exemption) 

81 are currently listed in 40 CFR part 161 and, with this final rule, will be listed in 40 CFR 

82 part 158.

83 C. What Action is the Agency Taking? 

84 The Environmental ProtectionThe Agency (EPA or the Agency) is revising and 

85 updating the data requirements for antimicrobial pesticides that are currently found in 

86 Title 40 of the Code of Federal Regulations (CFR) in part 161, and which are being 

87 relocated as revised by this rule to subpart W of part 158. Subpart W sets out data 

88 requirements specific to antimicrobial products that are described by the antimicrobial 

89 use patterns and use exposure considerations particular to antimicrobials. With the 

90 promulgation of part 158, subpart W, EPA is removing part 161, entitled “Data 

91 Requirements for Registration of Antimicrobial Pesticides” as it is no longer needed. 

92 Antimicrobial pesticides are used to control microbiological contamination in 

93 healthcare applications, and deterioration in industrial, commercial, and consumer 

94 products. Nearly 60 percent of antimicrobial products are registered as public health 

95 products (as defined at FIFRA 2(gg)) to control infectious microorganisms in hospitals 

96 and other health care environments. Public health products are intended to control 

97 microorganisms infectious to humans in any inanimate environment. The common 

98 public health antimicrobial products include sterilants, disinfectants, and sanitizers. 

99 Nonpublic health products are sold and distributed for use to control growth of algae, 

100 odor-causing bacteria, bacteria which cause spoilage, deterioration or fouling of 

101 materials and microorganisms infectious only to animals. Other examples of nonpublic 

102 health products include products used in cooling towers, jet fuel, paints, and treatments 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 5 of 233 

103 for textile and paper products. Within this final rule EPA is using the term antimicrobials 

104 to collectively refer to antimicrobial pesticides, antifoulant coatings and paints, and wood 

105 preservatives. The amendments contained in this final rule, which are discussed in 

106 detail in Units IV. through XXII. of this document, change the existing data requirements 

107 for antimicrobial pesticides in the following substantive respects:

108  By changing some of the existing data requirements, such as a change from 

109 conditionally-required to required, a change in the number of test species, or expanding 

110 the number of use patterns for which the test is required.

111  By adding newly codified data requirements, i.e., data requirements that are not 

112 currently identified in 40 CFR part 161, but are considered in current practice on a case113 by-case basis.

114  By adding new data requirements, i.e., data requirements that have not been 

115 required or have rarely been required in current practice on a case-by-case basis, and 

116 have not been routinely considered during the Agency’s evaluation of the data needed 

117 for the purpose of risk assessment. 

118  By eliminating the requirement for the chronic non-rodent study currently 

119 required in 40 CFR part 161.

120  By codifying the antimicrobial data requirements as finalized in this rule in 40 

121 CFR part 158, subpart W, and removing the current requirements that appear in 40 

122 CFR part 161. 

123 D. What are the Incremental Costs and Benefits of this Action?

124 The Economic Analysis (EA) of the potential costs and benefits associated with 

125 this action, as revised to address comments received on the proposed rule, is contained 

126 in a document entitled “Final Economic Analysis of Changes in Data Requirements for 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 6 of 233 

127 Antimicrobial Pesticides” (Ref. 1), a copy of which is in the docket, discussed in Unit 

128 XXII., and are briefly summarized here. 

129 1. Estimated costs. In its analysis, the Agency considered the potential, 

130 additional costs for the registration of new antimicrobial pesticides or new uses of 

131 currently registered antimicrobial pesticides, as well as the potential, additional costs 

132 incurred during the registration review of existing antimicrobial pesticides. 

133 The estimated total annual industry costs of the final rule is expected to be about 

134 $19.3 million. The difference between the baseline costs (the existing data 

135 requirements that were codified in 1984) and the cost of the Agency’s current practices 

136 is about $1 million annually. The difference between the baseline costs and the final 

137 rule costs, i.e., the incremental costs, is approximately $8.2 million annually assuming 

138 an estimated 15 new registrations. 

139 Under the final rule, the average cost per registration action of a new 

140 antimicrobial active ingredient is approximately $1 million to $5 million. For existing 

141 chemicals, data requirements in part 158, subpart W are relevant to the registration 

142 review program, and the average additional cost is estimated to be about $588,000 for 

143 wood preservatives, $284,000 for food and indirect food uses, and $260,000 for all 

144 other uses. For registration review, the total annual cost is $6.8 million.

145 EPA also conducted an analysis of the potential impact of this final rule on small 

146 entities, which is included in the EA and discussed in Unit XXV.C. In brief, EPA 

147 estimates that 500, or approximately 67 percent, of the unique parent companies that 

148 constitute the total universe of pesticide antimicrobial registrants, qualify as a small 

149 business. When considering both registration review and new registrations, on average 

150 each year about 30 small businesses are estimated to incur additional costs under this 

151 final rule. EPA estimates that about 23 small firms (almost 5 percent of the 500 small 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 7 of 233 

152 antimicrobial firms) may experience an economic impact of 3 percent or more of gross 

153 sales, As discussed later in this document, EPA has concluded based on this analysis 

154 that this potential impact is not a significant impact on a substantial number of small 

155 entities. 

156 2. Estimated benefits. In its analysis, EPA provides a qualitative discussion of 

157 the benefits, which are not quantifiable in the same monetary terms as the costs. In 

158 general, before manufacturers can sell pesticides in the United States, EPA must 

159 evaluate the pesticides thoroughly to ensure that they meet federal safety standards in 

160 FIFRA and FFDCA that were established to protect human health and the environment. 

161 EPA grants a "registration" or license that permits a pesticide's distribution, sale, and 

162 use only after the company meets the scientific and regulatory requirements. In 

163 evaluating a pesticide registration application, EPA assesses a wide variety of potential 

164 human health and environmental effects associated with use of the product. Applicants, 

165 or potential registrants, must generate or provide the scientific data necessary to 

166 address the identity, composition, potential adverse effects, and environmental fate of 

167 each pesticide. The information provided by the data requirements in this final rule allow 

168 EPA to evaluate whether an antimicrobial pesticide meets the applicable statutory 

169 standards.

170 Antimicrobials play an important role in public health and safety. While intended 

171 to provide health benefits of pathogen control or removal and, in some cases, safety 

172 benefits of materials preservation, they also involve risks of potential efficacy failure and 

173 exposure of hazards to humans and the environment. Therefore, the effectiveness and 

174 proper use of an antimicrobial pesticide is determined by EPA based on its evaluation of 

175 specific data that is provided as part of registration and registration review activities. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 8 of 233 

176 This final rule will enhance EPA’s ability to make sound regulatory decisions and 

177 help prevent the registration of pesticide products that may have unreasonable adverse 

178 effects on human health and the environment. The Agency believes that having the 

179 appropriate data ultimately leads to better risk management decisions, as well as 

180 provides the following other benefits:

181 a. More refined assessments mean less uncertainty and clearer understanding of 

182 actual risks. For example, EPA's current applicator/user exposure data base is not 

183 comprehensive, especially regarding exposures to pesticides in industrial and 

184 residential settings. Codifying these data requirements, many of which are currently 

185 applied on a case-by-case basis, would allow the Agency to conduct improved exposure 

186 assessments for applicators/users. This will benefit workers and consumers by allowing 

187 EPA to make better informed regulatory decisions that are neither too stringent nor too 

188 lenient.

189 b. Clarity and transparency to regulated community means savings. The 

190 enhanced clarity and transparency of the information presented in part 158, subpart W 

191 will reduce uncertainty for applicants in generating and submitting data that is necessary 

192 for EPA to be able to make registration decisions based on data-driven risk estimates 

193 that use fewer conservative assumptions. Applicants may save time and money by 

194 understanding which studies are needed to support the use of their product. Thus, the 

195 antimicrobial industry will, along with other partners in the regulated community, attain a 

196 better understanding of and can more efficiently participate in the pesticide registration 

197 process. This should allow products to enter the market earlier, thereby enabling 

198 registration of safer pesticides sooner and potentially reducing risks, as well as 

199 increasing profits. The clarity derived from having data requirements specific to 

200 antimicrobials may be especially important to small firms and new firms entering the 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 9 of 233 

201 industry who may have less experience than those firms that routinely work with the 

202 Agency.

203 c. EPA information assists other communities in assessing pesticide risks.

204 Scientific, environmental, and health communities find pesticide toxicity information 

205 useful to respond to a variety of needs. For example, medical professionals are 

206 concerned about the health of patients exposed to pesticides; poison control centers 

207 make use of and distribute information on toxicity and treatment associated with 

208 poisoning; and scientists use toxicity information to characterize the effects of pesticides 

209 and to assess risks of pesticide exposure. Similarly those responsible for protection of 

210 nontarget wildlife need reliable information about pesticides and assurance that 

211 pesticides do not pose an unreasonable threat. These data requirements will help the 

212 scientific, environmental, and health communities by increasing the breadth, quality, and 

213 reliability of Agency regulatory decisions by improving their scientific underpinnings.

214 d. Better informed users mean informed risk-reduction choices. Better regulatory 

215 decisions resulting from these data requirements also mean that the label will provide 

216 better information on the use of the pesticide. A pesticide label is the user's direction for 

217 using pesticides safely and effectively. It contains important information about where to 

218 use, or not use, the product, health and safety information that should be read and 

219 understood before using a pesticide product, and how to dispose of that product. This 

220 benefits users by enhancing their ability to obtain pesticide products appropriate to their 

221 needs, and to use and dispose of products in a manner that is safe and environmentally 

222 sound. 

223 e. Recognizes the unique down-the-drain uses associated with antimicrobials. 

224 For antimicrobial chemicals that go down-the-drain and eventually reach a WWTP, EPA 

225 intends to conduct an assessment of the potential impact of the antimicrobial chemical 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 10 of 233 

226 on the micro-organisms in the biological treatment processes of a WWTP and the 

227 potential for the antimicrobial chemical to pass through the WWTP in the effluent. The 

228 final rule will minimize costs to states and municipalities by ensuring that antimicrobial 

229 pesticide products registered under FIFRA don’t cause water quality problems or harm 

230 treatment facilities.

231 f. A milestone towards the Agency’s vision for 21st Century Toxicology and new 

integrated testing strategies. The Agency’s goal is to use 21st 232 Century science to 

233 increase the efficiency and effectiveness of our assessment process. This rule is a 

234 launching pad for that vision.

235 II. Background

236 A. Brief History of Pesticide Data Requirements

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

238 antimicrobial pesticides, antifoulant coatings and paints, and wood preservatives. EPA’s 

239 data requirements for pesticides were first published in 1984. Those data requirements 

240 were primarily influenced by agricultural uses. Since then, new risk concerns have 

241 been identified, and EPA’s statutory mandates for pesticide registration under FIFRA

242 and tolerance-setting under the FFDCA were amended in 1996 to require EPA to 

243 update the scientific underpinnings of risk assessments. The Agency must now perform 

244 more in-depth risk analyses, such as aggregate and cumulative risk assessments. 

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

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

247 and microbial pesticides (72 FR 60988). The rule development process for part 158, 

248 subpart W used the updated conventional pesticides data requirements as the starting 

249 point while considering the case-by-case data requirement decisions made over the 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 11 of 233 

250 years of registering antimicrobial pesticide products. The following four subparts in part 

251 158, promulgated in 2007, also apply to antimicrobial pesticides (see 40 CFR 158.1):

252  Subpart A: General Provisions

253  Subpart B: How to Use Data Tables

254  Subpart C: Experimental Use Permits

255  Subpart D: Product Chemistry

256 To provide continued regulatory coverage for antimicrobial pesticides until the 

257 Agency could promulgate a final regulation for antimicrobial pesticides, the 2007 final 

258 rule (72 FR 60251, October 24, 2007) (FRL 8116-2) preserved the original part 158 data 

259 requirements (promulgated in 1984) to apply to antimicrobial pesticides by 

260 redesignating them as part 161, This final rule finishes the promulgation of a final 

261 regulation for antimicrobial pesticides. Accordingly, EPA is also revoking 40 CFR part 

262 161.

263 B. How to Use the Data Tables

264 In establishing the data requirements in 1984, EPA adopted a step-wise 

265 approach to assist the applicant in determining the data needed to support the 

266 registration of a particular product. This approach, which is described in 40 CFR part 

267 158, subpart B, involves the use of “data tables” to facilitate the identification of the 

268 applicability of the data requirements. In essence, the data requirements illustrate the 

269 questions the registrant will need to answer about the safety of the pesticide product 

270 before the Agency can register it. Because of the variety of chemicals and use patterns, 

271 and because EPA must retain flexibility to tailor data requirements as appropriate, only 

272 qualitative descriptors are in the tables. Test notes provide more specific information on 

273 the applicability of specific data requirements.
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 12 of 233 

274 The table descriptors NR (not required), R (required), and CR (conditionally 

275 required) should be viewed as a general presentation, indicating the likelihood that the 

276 data requirement applies. The use of R does not necessarily indicate that a study is 

277 always required, but that it is more likely to be required than not. For example, if the 

278 applicant wanted to apply his pesticide to apples, then crop field trials would be required 

279 almost always on apples. However, if the physical/chemical properties of the chemical 

280 did not lend themselves to the test, such as performing an inhalation test with a 

281 chemical that is a solid and has an extremely low vapor pressure, then a waiver might 

282 be granted. Generally test notes for R studies discuss any particular circumstances 

283 when the testing might not be required.

284 The use of CR means a study is less likely to be required. Triggers in the test 

285 notes indicate the circumstances under which the Agency has learned through 

286 experience that the information is needed. Although only an approximation, if 

287 percentages were to be assigned to indicate the need for a particular study, then R 

288 could be viewed as representing the submission of a study 50% to 100% of the time 

289 and CR would be up to 50%.

290 Thus, NR, R, and CR are used for convenience to make the table format 

291 feasible, but serve only as a general indication of the applicability of a data requirement. 

292 In all cases, the test notes referred to in the table must be consulted to determine the 

293 actual need for the data. 

294 The table format includes a column heading entitled “Guideline,'' which refers to 

295 the OCSPP Harmonized Test Guidelines. Guideline numbers are provided as 

296 information/guidance to applicants. These Guidelines set forth recommended 

297 instructions and test methods for performing a study to generate the required data. 

298 Since these are guidance documents, the applicant is not required to use these 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 13 of 233 

299 Guidelines, but may instead seek to fulfill the data requirement by other appropriate 

300 means such as alternative test methods, submission of an article from open literature, 

301 or use of modeling. The applicant may submit a protocol of his own devising for the 

302 Agency to review. However, the OCSPP Harmonized Guidelines have been developed 

303 through a rigorous scientific process, including extensive peer review by the FIFRA 

304 Scientific Advisory Panel. Additionally, many of the Guidelines have been harmonized 

305 internationally. As such, they represent the recommended approach to developing high306 quality data that should satisfy EPA's data needs for risk assessment.

307 In addition, since it is not possible to sufficiently delineate all circumstances in 

308 test notes, consultation with EPA is encouraged. Applicants are also encouraged to visit 

309 the Agency's website at 

310 http://www.epa.gov/pesticides/regulating/data_requirements.htm.

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

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

313 This action is issued under the authority of sections 2, 3, 4, 5, 10, 12, and 25 of 

314 the Federal Insecticide and Rodenticide Act (FIFRA) as amended and section 408 of 

315 the Federal Food, Drug, and Cosmetic Act (FFDCA). The data required for a 

316 registration, reregistration, experimental use permit (EUP), or tolerance/tolerance 

317 exemption for antimicrobials are listed in 40 CFR part 158.

318 C. Next Steps after this Rulemaking

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

320 committed to improving and transforming ourthe Agency’s approach to pesticide risk 

321 management by enhancing ourthe Agency’s ability to use integrated approaches to 

322 testing and assessment. Over the next 5 years, The Pesticide Program plans to 

323 maximize use of existing data from similar compounds, including information from new 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 14 of 233 

324 in silico and in vitro predictive models and exposure modeling to target in vivo toxicity 

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

326 Over the next decade, as experience is gained and as ourthe Agency’s

327 understanding of toxicity pathways increases, an enhanced integrated testing and 

328 assessment approach will be implemented for all pesticides. The approach will fully 

329 integrate hazard and exposure information using advanced computer modeling of new 

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

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

332 of concern. Data from improved biomarkers of exposure and biological outcomes from 

333 population-based studies will be used to evaluate the effectiveness of this new risk 

334 assessment paradigm, to readily identify early effects in exposed populations, and to 

335 improve the approach. 

336 Current Agency scientific and regulatory practice provides the foundation for this 

337 final rule. While current practice is still largely dependent on animal (in vivo) testing, this 

338 rule is one milestone towards the Agency’s longer term vision for 21st Century 

339 Toxicology and new integrated testing strategies. OPP believes that certain classes of 

340 chemicals, such as antimicrobial pesticides, provide an appropriate starting point for 

341 OPP’s planned transformation. Many antimicrobials have both pesticidal and non342 pesticidal uses. In addition, many antimicrobial products are regulated under multiple 

343 jurisdictions. Thus, many antimicrobial chemicals have been assessed by other 

344 regulatory programs and agencies. The ready availability of published literature and 

345 publicly-available assessments offer a unique opportunity for the applicant to use the 

346 available information as a starting point for fulfilling data requirements, and, when 

347 appropriate, to use computer modeling and/or in-vitro data to supplement or fulfill data 

348 requirements. For example, OPP established a voluntary pilot program for eye irritation 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 15 of 233 

349 testing of certain antimicrobial pesticides using non–animal test methods. OPP will 

350 continue to evaluate use of new in vitro and computer-based approaches in ourOPP’s

351 hazard and risk assessment processes as the technologies are sufficiently developed 

352 and peer-reviewed. Certain tools are already available or anticipated to become 

353 available in the near term including, (Quantitative) Structure-Activity-Relationship 

354 (Q)SAR/expert systems and in vitro high through-put screening technologies. 

355 Furthermore, in conjunction with the International Life Sciences Institute (ILSI), OPP is 

356 currently pursuing the development of an application of the thresholds of toxicological 

357 concern (TTC) concept to evaluate antimicrobial pesticides. In collaboration with OPP, 

358 EPA’s Office of Research and Development is providing momentum for achieving the 

vision of 21st 359 Century Toxicology by developing and evaluating new technologies in 

360 molecular, cellular, and computational sciences to supplement or replace more 

traditional methods of data development. OPP believes that its goal of using 21st 361 

362 Century science in integrated approaches to testing and assessment is achievable with 

363 strong scientific and stakeholder support through a transparent process. As the 

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

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

366 evolving program needs as specified in § 158.30(c). See Unit V.C. and Unit XVIII. of 

367 the proposed rule for further discussion of EPA’s use of integrated approaches to 

368 testing and assessment.

369 D. Acronyms Used in this Document

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

371 ACGIH means the American Conference of Governmental and Industrial Hygenists

372 AD means EPA’s Antimicrobial Division in OPP

373 ARTCA means the Antimicrobial Regulation Technical Correction Act
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 16 of 233 

374 ASRI means Activated Sludge, Respiration Inhibition Test

375 ASSI means Activated Sludge Sorption Isotherm

376 ASTM means the American Society for Testing and Materials

377 AWPA means the American Wood Protection Association, formerly American Wood 

378 Preservatives Association

379 “CR” means conditionally required

380 CFR means the Code of Federal Regulations

381 CDC means the Centers for Disease Control and Prevention

382 COC means concentration of concern

383 CWA means the Clean Water Act

384 DCI means Data Call-in

385 D-t-D means down the drain

386 EA means economic analysis

387 EDSP means Endocrine Disrupter Screening Program

388 E-FAST means Exposure and Fate Assessment Screening Tool

389 EP means end-use product

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

391 ESA means the Endangered Species Act

392 EU means the European Union

393 EUP means experimental use permit

394 FDA means the Food and Drug Administration

395 FIFRA means the Federal Insecticide, Fungicide and Rodenticide Act

396 FFDCA means the Federal Food Drug and Cosmetic Act

397 FQPA means the Food Quality Protection Act

398 FWS means the United States Fish and Wildlife Service
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 17 of 233 

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

400 HSRB means the Human Studies Review Board

401 ICR means Information Collection Request

402 ILSA means International Life Sciences Institute

403 Kd means soil partition coefficient

404 Koc means soil organic carbon-water coefficient

405 Kow means octanol-water partition coefficient

406 MOR means magnitude of the residue

407 mg/L means milligrams per liter

408 NAICS means the North American Industrial Classification System

409 NAS means the National Academy of Sciences

410 NMFS means the United States National Marine Fisheries Service

411 NPDES means National Pollution Discharge Elimination System

412 NPRM means III. Public Comments on the Notice of Proposed Rulemaking

413 (NPRM)

414 “NR” means not required

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

416 Office of Pollution Prevention and Toxics (OPPTS)

417 OECD means Organisation for Economic Cooperation and Development

418 OMB means Office of Management and Budget

419 OPP means EPA’s Office of Pesticide Programs

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

421 OSHA means Occupational Safety and Health Administration

422 OW means EPA’s Office of Water

423 PPCP means pharmaceuticals and personal care products
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 18 of 233 

424 PEL means permissible exposure limit

425 ppb means parts per billion

426 ppm means parts per million

427 PPE means personal protective equipment

428 PRA means the Paperwork Reduction Act

429 PRIA means the Pesticide Registration Improvement Act

430 POTW means publicly owned treatment works

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

432 “R” means required

433 RAC means raw agricultural commodity

434 RED means Reregistration Eligibility Decision Document

435 RFA means the Regulatory Flexibility Act

436 RfC means Reference Concentration

437 RfD means Reference Dose

438 ROC means residue of concern

439 RQ means risk quotient

440 SAP means the FIFRA Scientific Advisory Panel

441 SAR means structure-activity-relationships

442 SBREFA means the Small Business Regulatory Enforcement Fairness Act

443 TGAI means technical grade active ingredient

444 TTC means threshold of toxicological concern

445 TEP means typical end-use product

446 TLV means threshold limit value

447 WET means whole effluent testing

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

Page 19 of 233 

449 WQC means Water Quality Criteria

450 WQS means Water Quality Standards

451 WWTP means wastewater treatment plant

452 USDA means United Stated Department of Agriculture

453 III. History of this Rulemaking

454 A. Background

455 EPA’s data requirements for pesticides were first published in 1984. Those data 

456 requirements were primarily influenced by agricultural uses. Since then, new risk 

457 concerns have been identified, and EPA’s statutory mandates for pesticide registration

458 under FIFRA and tolerance-setting under the FFDCA were amended in 1996Comments 

459 Submitted to require EPA to update the scientific underpinnings of risk assessments. 

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

461 cumulative risk assessments.EPA 

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

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

464 and microbial pesticides (72 FR 60988). The rule development process for part 158, 

465 subpart W used the updated conventional pesticides data requirements as the starting 

466 point while considering the case-by-case data requirement decisions made over the 

467 years of registering antimicrobial pesticide products. Four of the other subparts in part 

468 158, promulgated in 2007, also apply to antimicrobial pesticides (see 40 CFR 158.1). 

469 Those four subparts are:

470  Subpart A: General Provisions

471  Subpart B: How to Use Data Tables

472  Subpart C: Experimental Use Permits

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

Page 20 of 233 

474 As part of promulgating those final rules, on October 24, 2007, (72 FR 60251)

475 EPA preserved the original part 158 data requirements (promulgated in 1984), by 

476 redesignating them as part 161, to provide continued regulatory coverage for 

477 antimicrobial pesticides until the Agency could promulgate a final regulation for 

478 antimicrobial pesticides. This final rule finishes the promulgation of a final regulation for 

479 antimicrobial pesticides. Accordingly, EPA is also revoking part 161 today.

480 B. Discussion of the unit discusses, in general terms, the public comments received on 

481 the NPRM that appeared in the Federal Register of October 8, 2008 Notice of 

482 Proposed Rulemaking (NPRM)

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

484 establish data requirements specific to the registration of antimicrobial pesticide 

485 products in 40 CFR part 158, subpart W. The closing date of the 90–day ), and EPA’s 

486 responses to those comments. The comment period for the NPRM was extended from 

487 January 6, 2009 . The comment period was extended to April 6, 2009, to allow 

488 stakeholders additional time to assess the impact of the proposed revisions on their 

489 particular situations and submit their comments. In addition, EPA convened a public 

490 workshop in Arlington, Virginia, to explain the provisions of the NPRM on November 6, 

491 2008. The proposed rule, the notice of the extension of the comment period, the notice 

492 of the public meeting, the presentations used at the public meeting, the comments 

493 submitted, and EPA’s Response to Comments Document are available toin the public at 

494 http://www.regulations.gov (see docket EPA-HQ-OPP–2008–0110).for this rule.

495 C. Comments Submitted to EPA. 

496 During the public comment period, EPA received comments on the proposed part 

497 158, subpart W regulations from 29 entities. The breakdown of the origin of the 

498 comments is as follows:
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 21 of 233 

499  Antimicrobial Industry – 15 

500 o Lanxess Corporation

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

502 o Scientific and Regulatory Consultants, Inc.

503 o Antimicrobial Exposure Joint Venture (AEJV)

504 o Consumer Specialty Products Association (CSPA)

505 o Ecolab Inc.

506 o ISSA

507 o The Clorox Company

508 o Reckitt Benckiser

509 o Mason Chemical Company

510 o Proctor & Gamble

511 o Dow Chemical Company

512 o Johnson Diversey

513 o Troy Corporation

514 o American Chemistry Council (ACC)

515  Non-Governmental Organizations (NGOs) – 3 

516 o Environmental Working Group

517 o Humane Society

518 o Beyond Pesticides

519  Other – 3

520 o CropLife America

521 o Innovation and Reform Group

522 o Alternative Testing Working Group

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

Page 22 of 233 

524 o Health Canada 

525  Water Agencies – 7

526 o Hampton Roads Sanitation District

527 o California Association of Sanitation Agencies

528 o National Association of Clean Water Agencies

529 o San Francisco Department of the Environment

530 o Sanitation Districts of Los Angeles County

531 o Tri-Tac

532 o California Stormwater Quality Association

533 There were also late comments from ACC, received at meetings held at EPA in 

534 Arlington, VA on December 2, 2009, and June 14, 2010. Most recently,, as well as at a 

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

536 provided additional late comments. The presentation materials and EPA’s summary of 

537 the meetings, and the letter with attachments are included in the docket at 

538 http://www.regulations.gov. The. These late comments submitted by ACC and/or 

539 CSPA were not new comments, but rather re-statements of issues presented in their 

540 original comments submitted to EPA. 

541 A, and are also available in the docket. Another late comment cosigned by the 

542 Physicians Committee for Responsible Medicine, the Humane Society International, and 

543 People for the Ethical Treatment of Animals was submittedreceived on September 1, 

544 2010. This late comment did contain several new issues, which, that were addressed 

545 by adding the additional comments and responses to the toxicology section of the 

546 Response to Comments Document. 

547 EPA carefully reviewed all comments submitted., and provides responses in the . 

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

Page 23 of 233 

549 Response to Comments Document is in the docket at http://www.regulations.gov. As 

550 previously discussed, the Response to Comments Documentalso contains the rationale 

551 for the changes that were made from the proposed rule to the final rule, in response to 

552 submitted comments. Similar comments are grouped together. EPA selected the most 

553 significant of the comments, such as thoseComments that impacted thehad a 

554 substantive impact on changes from the proposed rule to the final rule, for inclusion are 

555 also discussed in Units IV. to XXII. of this final ruledocument. 

556 D. B. Overview of this Final Rule 

557 1. In general. This final rule reflects updates and revisions to the data 

558 requirements currently contained in 40 CFR part 161, in many cases by codifying the 

559 case-by-case data requirements decisions made over the years to help apply the 

560 agriculturally-based 1984 data requirements to antimicrobial pesticide products. The 

561 antimicrobial data requirements are being addedrelocated to 40 CFR part 158, subpart 

562 W. , and 40 CFR part 161 is being removed. This final rule will further enhance the 

563 Agency's ability to make regulatory decisions about the human health, and 

564 environmental fate and effects of antimicrobial pesticide products. 

565 Based on comments received, EPA revised the proposed data tables. EPA’s 

566 Response to Comments Document is in the docket at http://www.regulations.gov. That 

567 document contains the rationale for the changes that were made from the proposed rule 

568 to the final rule, in response to submitted comments. 

569 Eleven new data requirements for antimicrobial pesticides are being codified 

570 today.in this final rule. As discussed in the preamble to the proposed rule (73 FR 

571 59387),, a “new” data requirement “means that the data requirement has never been 

572 required or has rarely been required on a case-by-case basis, and has not been 

573 routinely considered during the Agency’s evaluation of the data needed for the purpose 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 24 of 233 

574 of risk assessment.” ” (73 FR 59387). Eight new data requirements that were proposed 

575 in 2008 and are now being codified are: Developmental neurotoxicity; immunotoxicity; 

576 photodegradation in soil; soil residue dissipation; ready biodegradability study; porous 

577 pot study; activated sludge sorption isotherm study; and modified activated sludge, 

578 respiration inhibition test. The developmental neurotoxicity and immunotoxicity tests are 

579 new compared to part 161, but were added for conventional pesticides in the 2007 

580 amendments to part 158. The photodegradation in soil study was not previously 

581 required for wood preservatives. The other four studies are unique to antimicrobials. 

582 Since the proposed rule, Based on comments received, three two other “new”

583 data requirements are also being added: that serve as alternatives to tests that were 

584 proposed (and are now being finalized): Simulation tests to assess the biodegradability 

585 of chemicals in discharged wastewater, and simulation test – aerobic sewage treatment: 

586 activated sludge units, and . Similarly, also based on comments, one ”new” data 

587 requirement, the nature of the residue on surfaces, is being added as a more definitive 

588 trigger or screen for determining whether one of the studies that was proposed – the 

589 migration study – must be conducted. 

590 Additionally, this final rule: 

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

592 part 161, but have typically been required to register an antimicrobial pesticide product. 

593  Provides improved definitions for antimicrobial pesticides used for public 

594 health and nonpublic health purposes. 

595  Codifies data requirements to determine risks to waste water treatment plants 

596 (WWTPs) and the potential for movement of antimicrobials and their degradates from 

597 the indoor environment to the outdoor environment via effluent discharge from a 

598 publically owned treatment work (POTW). 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 25 of 233 

599 The data requirements promulgated todayin this final rule identify the types of 

600 information that EPA needs to determine whether aan antimicrobial pesticide product 

601 should be registered, and to make decisions regarding tolerances or tolerance 

602 exemptions for pesticide residues in food. Subpart W includes a series of tables and 

603 regulatory text that mirrors the structure of the data requirements for conventional 

604 pesticides. However, subpart W establishes specific data requirements for each 

605 scientific discipline (except product chemistry) for antimicrobial pesticides. As explained 

606 in Unit IIIA.,II.A. of this document, subpart D to part 158, which contains the product 

607 chemistry data requirements for conventional pesticides, also applies to antimicrobials. 

608 The order of subpart W also mirrors that of the larger part 158. As such, the following 

609 data requirements categories are included in detail in part 158, subpart W: Product 

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

611 (both application and post-application human exposures), residue chemistry, and 

612 environmental fate requirements. 

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

614 rule (73 FR 59389-90, October 8, 2008). As part of today’s actionthis final rule, EPA 

615 has developed and will shortly post on the Agency’s website an Antimicrobial Use Site 

616 Index to provide additional information about these use patterns. This index is included 

617 in the docket and is posted on the Agency’s website.

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

619 antimicrobial pesticide decisions. These efforts are expected to help protect human 

620 health and the environment by providing an up-to-date scientific framework for 

621 identifying and assessing the risks of antimicrobial pesticides sold or distributed in the 

622 United States. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 26 of 233 

623 2. Changes to thefrom what was proposed rule. In response to comments, EPA 

624 has made numerous changes to the proposed rulerequirements in crafting the final rule

625 promulgated today. The most significant changes are summarized belowas follows. 

626 i. Alternatives to the porous pot study. With regard to the porous pot study in the 

627 final Environmental Fate Data Requirements Table in § 158.2280, EPA is adding two 

628 simulation studies that can serve as an alternative to the porous pot study. This change 

629 was based on a comment that requested consideration of whether “studies that simulate 

630 wastewater treatment plants (WWTPs) [could] substitute for [the porous pot study].” 

631 (ACC Comment identified in the docket at http://www.regulations.gov;by document ID 

632 number EPA-HQ-OPP-2008-0110-0088.9; Appendix H, entitled “Comments on 

633 Proposed Data Requirements for Environmental Fate” p. 5). Additionally, in the 

634 commenter’s suggested environmental fate data requirements table (p. 11), instead of 

635 giving the title of the study as “Porous Pot,” the commenter wrote “Simulated WWTP; 

636 e.g., Porous Pot Study.” 

637 EPA agreed with the commenter and identified two other studies: The 

638 biodegradation in activated sludge study as described in the OPPTS guideline entitled 

639 “Simulation Tests to Assess the Biodegradability of Chemicals Discharged in 

640 Wastewater” and simulation test – aerobic sewage treatment: activated sludge units. 

641 This change provides applicants with more flexibility in meeting this data requirement. 

642 EPA’s rationale is described in Unit XV.A,., and for greater detail see response to 

643 comment 134.1 in the Response to Comments Document in the docket at 

644 http://www.regulations.gov). Testnote). Test note 3 to the final Environmental Fate 

645 Data Requirements Table in § 158.2280 clearly specifies that only one biodegradation 

646 study is to be submitted. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 27 of 233 

647 In creating a tiered structure for the Antimicrobial Environmental Fate Data 

648 Requirements table, the table and accompanying test notes are intended to be used to 

649 determine which antimicrobials would be expected to reach a WWTP. Test notes 18, 

650 19, 20, and 21 to the Environmental Fate Data Requirements table discuss specific 

651 criteria for determining whether data from a biodegradation study, the activated sludge 

652 sorption isotherm study, and the activated sludge respiration inhibition test are required 

653 for a particular product based on its intended uses.

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

655 migration study in the final Residue Chemistry Data Requirements in § 158.2290. In its 

656 proposed rule, EPA “triggered” the migration study based on anticipated instances such 

657 as theoretical (modeled) estimates yielding a risk of concern. One commenter 

658 submitted a suggested residue chemistry data requirements table with a line-item 

659 entitled “Nature of residue of surface.” (ACC Comment, identified in the docket at 

660 http://www.regulations.gov;by document ID number EPA-HQ-OPP-2008-0110-0088.10; 

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

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

663 data requirements table, which also included the same line-item entitled “Nature of 

664 residue on surface.” (CSPA Comment, identified in the docket at 

665 http://www.regulations.gov;by document ID number EPA-HQ-OPP-2008-0110-0086.2). 

666 The commenters’ suggestion of requiring a nature of the residue study on 

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

668 nature of the residue on surfaces study. As specified in testnote 3test note 5 to the final 

669 Residue Chemistry Data Requirements Table, the results of the nature of the residue on 

670 surfaces study will serve as a trigger for determining whether the migration study will 

671 need to be performed. EPA considers the commenters’ suggestions to be a valuable 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 28 of 233 

672 addition to the final Residue Chemistry Data Requirements Table in § 158.2290 that 

673 provides more definitive triggers to help define and narrow the instances of higher-tiered 

674 testing. 

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

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

677 product is dependent upon where the product is intended to be used (land-only versus 

678 land and aquatic). This approach also assumes that diversion does not occur and that 

679 wood that is treated for land-only uses does not end up in the water and vice versa. In 

680 practice, it is difficult to assure that diversion does not occur. Accordingly, in response 

681 to comments, the Agency determined that all treated wood needs to be considered as 

682 having the potential to come into contact with surface water. Therefore, for the final 

683 Environmental Fate Table, for the wood preservatives column, the data requirements for 

684 anaerobic soil metabolism, aerobic aquatic metabolism, and anaerobic aquatic 

685 metabolism were changed from “CR” to “R.” For the final Nontarget Organism Table, 

686 for the wood preservatives column, the data requirements for chronic toxicity testing 

687 with fish (fish early-life stage) and aquatic invertebrate (aquatic invertebrate life-cycle) 

688 are being changed from “CR” to “R” to provide chronic data when chronic exposure is 

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

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

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

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

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

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

695 toxicity to WWTP microorganisms in an activated sludge basin. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 29 of 233 

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

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

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

699 the active ingredient is likely to be transferred to the bottom of the water column, and 

700 then be adsorbed to the sediment. Therefore, EPA is changing, in the final 

701 Environmental Fate Data Requirements Table, the “CR” for the aquatic sediment study 

702 for the antifoulant paint and coatings column to “R.” With regards to the three acute 

703 toxicity tests conducted with the TEP, the “NR” in the antifoulant paint and coatings 

704 column is changed to “CR.” Also, to perform a down -the -drain analysis, the Agency is 

705 requiring data on the biodegradation of an antifoulant and its potential toxicity to WWTP 

706 microorganisms in an activated sludge basin. 

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

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

709 likely that EPA would model this route and pathway of exposure using inputs from 

710 available and reliable published research. Therefore, EPA has removed this data 

711 requirement from the final Post-Application Exposure Table. 

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

713 requirement tables. In the proposed rule, for the toxicology data requirements table, 

714 EPA separated those use patterns needing more toxicology data from those needing 

715 less toxicology data using a terminology described as high or low. Based on comments 

716 received, in this final rule, EPA is now using a food/nonfood approach with some 

717 similarities to that of the toxicology data requirements table for conventional pesticides 

718 to distinguish the use patterns that need more toxicity data from those that need less. 

719 The food-use column and the nonfood-use column are split into subcolumns to explain 

720 which food-uses or nonfood-uses require more data, and which require less. This 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 30 of 233 

721 modification of the food/nonfood approach delineates the specific data requirement 

722 needs for antimicrobial pesticides. 

723 For the final Residue Chemistry Data Requirements Table, EPA has adopted the 

724 commenters’ suggestion for a tiered format. After review of the commenter’s suggested 

725 tables, EPA believes the commenters’ suggested tiered approach is more suitable to 

726 antimicrobials than that proposed by EPA. 

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

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

729 “unsubstantiated assignment of exposure categories” (ACC Comment, identified in the 

730 docket at http://www.regulations.gov;by document ID number EPA-HQ-OPP-2008-

731 0110-0088.1, p. 21 and 22). EPA continues to believe that the use of “high” and “low” 

732 categories of exposure defined by the antimicrobial use patterns are a valid method for 

733 identifying those exposures that have greater exposure and those that have less. 

734 Based on its experience, EPA understands which use patterns require more data. 

735 However, EPA can achieve the same result without the use of the terms “high” or “low.” 

736 Therefore, based on comments received, EPA notes that it is no longer using the terms 

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

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

739 the terms “high environmental exposure” and “low environmental exposure” as table 

740 headers for the final Antimicrobial Nontarget Organism, the Nontarget Plant Protection, 

741 or the Environmental Fate Data Requirements Table. However, EPA also notes that 

742 terms such as “high human exposure,,” “low human exposure,,” “high environmental 

743 exposure” and “low environmental exposure” can be appropriate when discussing a 

744 particular antimicrobial use. A statement that a particular use results in, for example, 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 31 of 233 

745 “high environmental exposure” provides information and alerts the reader that more 

746 data are likely to be needed, rather than less data. 

747 IV. Scope of the Rule 

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

749 Regulations (CFR) for EPA’s data requirements under FIFRA and FFDCA section 408 

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

751 characteristics of antimicrobial pesticides, it builds upon the existing data requirements 

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

753 pertaining to conventional pesticides. Both sets of data requirements – conventional 

754 and antimicrobial – are designed to provide EPA with the information needed to make 

755 the required regulatory determinations under FIFRA and FFDCA section 408. FIFRA 

756 provides that a pesticide may not be registered for sale, distribution, and use unless “it 

757 will perform its intended function without unreasonable adverse effects on the 

758 environment . . . .” [7 U.S.C. 136a(c)(5)(C)]. FIFRA defines “unreasonable adverse 

759 effects on the environment” as both “any unreasonable risk to man or the environment” 

760 and “a human dietary risk . . . inconsistent with the standard under section 408 of the 

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

762 tolerance permitting pesticide residues in food unless EPA determines that the 

763 tolerance is “safe” [21 U.S.C. 346a(b)(2)(A)(i)]. “Safe,” under FFDCA section 408, is 

764 defined as “a reasonable certainty that no harm will result from aggregate exposure to 

765 the pesticide chemical residue, including all anticipated dietary exposures and all other 

766 exposures for which there is reliable information” [21 U.S.C. 346a(b)(2)(A)(ii)]. In 

767 making safety determinations, EPA is required to consider aggregate and cumulative 

768 exposures from pesticides and other related substances and multiple factors specifically 

769 related to the protection of children [21 U.S.C. 346a(b)(2)(C) and (D)]. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 32 of 233 

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

771 its composition, toxicity, potential human exposure, environmental properties, and 

772 ecological effects, as well as information on its product performance (efficacy) in certain 

773 cases” (73 FR 59384, October 8, 2008). Since 1984, EPA has had codified FIFRA data 

774 requirements mandating data on, among other things, the toxicity hazards from 

775 ingestion of pesticides and exposure levels of pesticide residues in food (Ref. 12). With 

776 the passage in 1996 of the Food Quality Protection Act, [Public Law 104-170, 110 Stat. 

777 1489 (1996)], which added the expanded safety standard in FFDCA section 408 

778 described abovepreviously, EPA’s data needs have expanded. As noted in the 

779 preamble to the proposed rule, “[t]he combination of aggregate and cumulative 

780 exposure assessments required by FFDCA section 408 increases the nature and scope 

781 of EPA’s risk assessment, and potentially increases the types and amounts of data 

782 needed to determine that the FFDCA safety standard is met” (73 FR 59385, October 8, 

783 2008). Moreover, with the explicit linkage in FIFRA between the FIFRA and FFDCA 

784 section 408 safety standards (also added by FQPA), “[t]he data required to support a 

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

786 the data needed for an ‘unreasonable adverse effects’ determination under FIFRA” [Id.; 

787 see 72 FR 60934 (, October 26, 2007) ( (FRL 8106-5), recodifying part 158 data 

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

789 establishing specific data requirements for antimicrobial pesticides is designed to 

790 capture the broad range of data needed to assess the safety of pesticides under the 

791 standards of both FIFRA and FFDCA section 408. 

792 The ACC Biocides Panel and other commenters, however, have claimed that the 

793 scope of the proposed rule exceeds the EPA’s statutory authority because EPA is 

794 asserting “jurisdiction under FIFRA over some antimicrobial food uses where, in the 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 33 of 233 

795 Panel’s view, the statutory scheme provides exclusive jurisdiction to FDA” (Food and 

796 Drug Administration)). (ACC Comment identified in the docket at 

797 http://www.regulations.gov;by document ID number EPA-HQ-OPP-2008-0110-0088.1,

798 p. 31). Although the ACC Biocides Panel acknowledges that these uses are properly 

799 regulated by EPA as “pesticides” under FIFRA, the Panel argues that “EPA’s 

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

801 for registration under FIFRA, taking into account FDA’s existing regulatory finding 

802 [under FFDCA section 409]. . . . EPA does not have the authority under either FIFRA 

803 or FFDCA to review or change the terms of the FDA approval.” (ACC Comment,

804 identified in the docket at http://www.regulations.gov;by document ID number EPA-HQ805 OPP-2008-0110-0088.1, p.33). In essence, the Panel is asserting that for these 

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

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

808 has evaluated the safety of the use of the substance under section 409. As a basis for 

809 this argument, the ACC Biocides Panel points to the Antimicrobial Regulation Technical 

810 Corrections Act (ARTCA), [Public Law 105-324, in 1998], which divided FFDCA 

811 jurisdiction between EPA and FDA with respect to antimicrobials. The Panel further 

812 argues that EPA is wrong to rely on FIFRA section 2(bb)’s inclusion of the FFDCA 

813 section 408 safety standard in the definition of “unreasonable adverse effects” as 

814 authority for requiring data on antimicrobial uses falling under FDA’s FFDCA section 

815 409 jurisdiction. Labeling EPA’s interpretation of FIFRA section 2(bb) in the proposed 

816 rule as “new,” the ACC Biocides Panel claims that EPA has contradicted its “long817 standing” interpretation of this provision. 

818 The ACC Biocides Panel fundamentally misunderstands EPA’s statutory 

819 authority under FIFRA to require data pertaining to dietary risk from pesticides. EPA’s 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 34 of 233 

820 authority to regulate pesticides under FIFRA with regard to their dietary risk is derived 

821 from FIFRA not the FFDCA. Under FIFRA, EPA is charged with protecting the public 

822 from “unreasonable adverse effects on the environment.” As noted abovepreviously, 

823 FIFRA in section 2(bb) defines “unreasonable adverse effects” in the first instance as 

824 “any unreasonable risk to man . . . .” [7 U.S.C. 346(bb)]. This broad standard clearly 

825 encompasses any unreasonable dietary risk. EPA’s authority to regulate pesticides 

826 under FIFRA on the basis of dietary risk is explicitly reinforced by the second part of the 

827 unreasonable adverse effects standard which directs EPA to evaluate “human dietary 

828 risks” from “pesticides” under the safety standard in FFDCA section 408. [Id.] 

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

830 to regulate pesticides based on dietary risk under FIFRA section 2(bb). The FIFRA 

831 section 2(bb) standard is independent from the safety standard under FFDCA section 

832 409. Further, any finding by EPA under FIFRA that considers dietary risk would not 

833 “change the terms of a FDA approval;” rather, it would simply be a determination as to 

834 whether the separate FIFRA regulatory standard had been met. Finally, contrary to the 

835 ACC Biocides Panel’s contention, the adjustment by the ARTCA of EPA’s and FDA’s 

836 jurisdiction under FFDCA sections 408 and 409 over antimicrobials does not affect 

837 EPA’s jurisdiction or authority with regard to dietary risks of pesticides under FIFRA. In 

838 fact, as explained belowfurther in this unit, not only did the ARTCA not amend FIFRA 

839 section 2(bb) but Congress in the ARTCA took the unusual step of expressly 

840 disavowing any intent to narrow the scope of EPA’s authority under FIFRA. 

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

842 which, among other things, changed EPA and FDA jurisdiction under FFDCA sections 

843 408 and 409. Prior to 1996, section 408 of the FFDCA, which is administered by EPA, 

844 only applied to “pesticide chemicals” that were defined as FIFRA “pesticides” “used in 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 35 of 233 

845 the production, storage, and transportation of raw agricultural commodities” [21 U.S.C. 

846 321(q) (1994)]. FIFRA pesticide residues in food not falling within this provision (i.e. 

847 FIFRA pesticides used later in the food production process than the growth of raw 

848 agricultural commodities) came under section 409 of the FFDCA as food additives [See 

849 21 U.S.C. 321(s), 348 (1994)]. FDA administers the establishment of food additive 

850 regulations under FFDCA section 409. Many antimicrobial pesticides used in 

851 conjunction with the manufacturing and processing of foods, at that time, were regulated 

852 as food additives. This division of legislative authority was changed by the FQPA in 

853 1996. The FQPA amended the definition of “pesticide chemical” in the FFDCA to make 

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

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

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

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

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

859 all FIFRA pesticides under FFDCA section 408. Not only did Congress consolidate 

860 regulation of all pesticide residues in FFDCA section 408 but it also amended FIFRA to 

861 insure that the new safety standard in FFDCA section 408 was part and parcel of the 

862 FIFRA registration standard for pesticides resulting in residues in food [7 U.S.C. 

863 136(bb)(2)]. Specifically, as noted above, in section 2(bb)(2), Congress defined an 

864 “unreasonable adverse effect on the environment” under FIFRA as “a human dietary 

865 risk from residues that result from a use of a pesticide in or on any food inconsistent 

866 with the standard under FFDCA section 408 of the Federal, Food, Drug, and Cosmetic 

867 Act [21 U.S.C. 346a].” 

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

869 consolidate all pesticide chemical residues in foods under FFDCA section 408. ARTCA 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 36 of 233 

870 amended the definition of “pesticide chemical” in FFDCA section 201 to exclude certain 

871 antimicrobial substances from the coverage of the definition [See 21 U.S.C. 321(q)]. 

872 More specifically, with certain qualifications, the ARTCA excepted, from the definition of 

873 pesticide chemical, substances that are FIFRA pesticides and are “applied for [an 

874 antimicrobial] use on food, or the substance is included for such use in water that 

875 comes into contact with food, in the preparing, packing, or holding of the food for 

876 commercial purposes.” [21 U.S.C. 321(q)(1)(B)(i)]. In addition, ARTCA excepted 

877 substances from the definition of pesticide chemical that are food contact substances, 

878 as defined in section 409(h)(6) of the FFDCA, based on certain circumstances related to 

879 their use. These antimicrobial substances were now no longer considered “pesticide 

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

881 the effect of shifting the residues resulting from these antimicrobial substances from 

882 FFDCA section 408 to FFDCA section 409 and shifting agency jurisdiction under the 

883 FFDCA over the same from EPA to FDA. Importantly, Congress, in ARTCA, did not 

884 amend FIFRA to remove these uses of antimicrobial substances from the definition of 

885 “pesticide” under FIFRA and left unchanged FIFRA section 2(bb)(2) which mandates 

886 that the section 408 safety standard is part of FIFRA’s unreasonable adverse effects 

887 standard as to FIFRA “pesticide” residues on food. Thus, EPA retained FIFRA 

888 jurisdiction over these antimicrobial substances (because they remained FIFRA 

889 “pesticides”) while FDA re-acquired FFDCA jurisdiction over them under FFDCA section 

890 409 (because they were removed from the definition of “pesticide chemical”). To make 

891 clear its intent on EPA’s FIFRA jurisdiction, the ARTCA included the following express 

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

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

894 to the Federal Insecticide, Fungicide, and Rodenticide Act, this clause 

895 [excluding certain antimicrobial substances from the FFDCA definition 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 37 of 233 

896 of “pesticide chemical”] does not exclude any substance from such 

897 definition” [21 U.S.C. 321(q)(1)(B)]. 

898 

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

900 language, excluding the designated antimicrobial substances from the coverage of 

901 FFDCA section 408 but continuing to regulate those antimicrobial substances that 

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

903 pesticides result in residues in food, the risks from such residues be consistent with the 

904 safety standard in FFDCA section 408. After all, FIFRA section 2(bb)(2), on its face, 

905 applies to FIFRA “pesticides” and not FFDCA “pesticide chemicals.” Any other result 

906 would be directly contrary to Congress’ dictate that it was not excluding any substances 

907 from the FIFRA definition of “pesticide.” Accordingly, it is well within EPA’s FIFRA 

908 authority to require that data be submitted on pesticides to determine if those pesticides 

909 meet the FFDCA section 408 safety standard, whether or not those pesticides come 

910 within the definition of a FFDCA “pesticide chemical,” so long as the use of those 

911 pesticides results in residues in food. On the other hand, the ACC Biocides Panel’s 

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

913 specifically rejected by the Congress when it passed ARTCA. 

914 There is no basis for the ACC Biocide Panel’s claim that EPA’s interpretation of 

915 FIFRA section 2(bb)(2) is “new.” The best evidence of the consistent and long-held 

916 nature of EPA’s interpretation are the numerous submissions to the Agency from the 

917 Panel (and others) over the last 10 years disputing EPA’s plain language approach to 

918 FIFRA section 2(bb)(2). (Refs. 2, 3, 4, 5, 6, 7, 8, 9, 10 and 1011) 

919 V. Discussion of SeveralV. Issues Repeated Throughout Most Comments
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 38 of 233 

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

921 noted that four specific comments were routinely repeated throughout most of the entire 

922 set of comments. 

923 A. Differentiating the Review of Antimicrobials

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

925 3(h)(3)(A)(ii) specifies that EPA must differentiate the review of antimicrobial pesticides 

926 from that of other pesticides. 

927 2. EPA’s response. FIFRA section 3(h)(3)(A)(ii) specifies, among other things, 

928 that, in proposed regulations to accelerate and improve the review of antimicrobial 

929 pesticide products, EPA shall define the various classes of antimicrobial use patterns, 

930 differentiate the types of review undertaken for antimicrobial pesticides, conform the 

931 degree and type of review to the risks and benefits presented by antimicrobial 

932 pesticides, and ensure that the registration process is sufficient to maintain antimicrobial 

933 product efficacy. While those elements apply to a proposed rulemaking that the Agency 

934 published on September 17, 1999 (64 FR 50671) (FRL 5770-6), the Agency has been 

935 mindful of those same elements in its development of part 158, subpart W. As applied 

936 to antimicrobial product registration actions, differentiation refers to the tailoring of data 

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

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

939 requirements applied to antimicrobials are designed to respond to the special or unique 

940 needs of antimicrobials such as the nature of the products, their ingredients, their uses, 

941 etc. Differentiation or tailoring does not mean that the resulting data requirements for 

942 antimicrobials will necessarily be comprised of more, less, or the same number and type 

943 of data requirements as required for other types of pesticides such as conventional 

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

Page 39 of 233 

945 For example, the residue chemistry data requirements for conventional 

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

947 fields. However, the residue chemistry data requirements for antimicrobials, codified 

948 todayin this final rule, have been tiered to account for applications that focus not on 

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

950 for antimicrobial uses, including those that result in residues on food more indirectly, 

951 such as from use as sanitizers in food processing plants. The overall impact is to 

952 require fewer studies since the tiering used for the antimicrobial residue chemistry data 

953 requirements table is structured differently, and there are fewer “R” studies and most 

954 studies are “CR.” However, there are two residue chemistry data requirements 

955 (migration and nature of the residue on surfaces) for antimicrobials that are not included 

956 in the conventional residue chemistry data requirements table because they reflect the 

957 unique use sites for antimicrobials; see Unit XVI. for additional discussion. Ecotoxicity 

958 and environmental fate data requirements provide another example of the differentiation 

959 of data requirements between antimicrobials and conventional pesticides. While 

960 conventional or biochemical/microbial pesticides are often used outdoors, and are 

961 deliberately placed/spread in the environment, most antimicrobials are used indoors. 

962 As discussed in the preamble (73 FR 59406), previously EPA had assumed that many 

963 of the indoor uses went down -the -drain to a waste water treatment plant (WWTP),,

964 where the WWTP processes would mitigate environmental concerns. Therefore, in 

965 1984, EPA required basic ecotoxicity and environmental fate data for conventional 

966 pesticides but made these types of data conditional for indoor uses such as 

967 antimicrobials based on whether antimicrobial-specific data indicated that environmental 

968 exposure may occur. However, as discussed in the proposed rule (73 FR 59407), in 

969 recent years there have been detections of antimicrobial chemicals (with indoor uses) in 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 40 of 233 

970 waterbodies. These antimicrobials are moving into the environment via treated effluent. 

971 Therefore, EPA is requiring for antimicrobials a specific tiered-set of data to evaluate the 

972 likelihood of environmental exposure to antimicrobials that may reach a WWTP, as a 

973 result of being washed down the drain via leachates, rinsates, and flushes. These data 

974 evaluate whether antimicrobials are likely to survive the treatment processes at a typical 

975 WWTP, and thus would be present in the WWTP effluent. Antimicrobials that do 

976 survive the treatment processes have the potential to end-up in the terrestrial or aquatic 

977 environments and higher-tiered ecotoxicity and environmental fate data are only 

978 triggered for these antimicrobials. 

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

980 in the nature of the particular type of pesticide's use.pesticide used. Even with such 

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

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

983 data requirements. EPA’s ultimate goal with its antimicrobial data requirements is to 

984 create a body of data requirements which produce sufficient information for the Agency 

985 to consider and use in making its statutorily-required determinations regarding the risks 

986 and benefits, where applicable, of antimicrobial pesticides. The differentiation or 

987 tailoring of the antimicrobial data requirements is instrumental in accomplishing that 

988 goal. 

989 B. Rewrite and Repropose the Rule

990 Several commenters requested that EPA rewrite and then repropose this rule. 

991 Commenters raised three arguments as to why EPA should repropose. First, the 

992 proposed regulation does not contain scientifically-based criteria for determining data 

993 requirements but instead requires that data requirements be determined in case-by994 case consultations in which EPA retains “sole discretion” as to the data required. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 41 of 233 

995 Second, EPA has not disclosed how it plans to use the proposed data in EPA risk 

996 assessments. Third, affected parties cannot properly evaluate the data requirements 

997 without final guidelines on how such studies should be conducted. Each of these three 

998 arguments are addressed in detail belowin the following responses. 

999 1. Comment on scientifically-based criteria. Several commenters focused on the 

1000 testnotestest notes to the data requirements tables, and claimed that the proposed rule 

1001 “leaves too many standards and decisions to the sole discretion of EPA, creating 

1002 uncertainty and, inevitability, inconsistency in regulatory decision making.” Too many 

1003 determinations, the commenter asserted, are at “EPA’s discretion” because the 

1004 proposal is vague, without clear-cut criteria. Additionally, they argued that there are too 

1005 many places in the test notes where consultation with the Agency is required or the 

1006 phrase “as determined by the Agency” is used. (One commenter listed 37 instances in 

1007 which the proposal allegedly substituted a mandatory consultation process for 

1008 regulatory criteria.) According to the commenters, EPA should eliminate most of the 

1009 consultation requirements and instead, repropose the rule providing a clear set of 

1010 requirements. 

1011 2. EPA’s response to comment on scientifically-based criteria. Test notes often 

1012 contain qualitative or quantitative measures for use in determining whether a study is 

1013 triggered or not. Most frequently this occurs when there is an initial study that relates to 

1014 whether subsequent testing would be needed or not. Not all triggers are easily 

1015 reduceable to quantitative measures and EPA believes that qualitative descriptors such 

1016 as “expected to enter the environment in significant concentrations,” or “if repeated 

1017 dermal exposure is likely to occur under conditions of use,” and “the use of the pesticide 

1018 is likely to result in repeated human exposure over a limitedconsiderable portion of the 

1019 human lifespan” provide meaningful criteria for determining when a study is triggered. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 42 of 233 

1020 EPA has carefully reviewed each of the 37 test notes cited by one commenter and has 

1021 identified several instances in which clarification of the criteria was appropriate. EPA’s 

1022 analysis of these 37 test notes and resultant changes are included in response to 

1023 comment 3 in the Response to Comments Document in the docket at 

1024 http://www.regulations.gov.. 

1025 In numerous places the test notes contain language stating that the criteria would 

1026 be applied “as determined by the Agency.” Commenters have misinterpreted this as 

1027 giving EPA the authority to make decisions on factors other than the regulatory criteria 

1028 included or in its “sole discretion.” This was not EPA’s intent and, accordingly, EPA has 

1029 removed all of the phrases “as determined by the Agency” from all test notes for the 

1030 final antimicrobials rule so there can be no chance of a misunderstanding of how the 

1031 criteria are to be applied. 

1032 Commenters also asserted that the EPA’s alleged mandatory consultation 

1033 requirements rendered the test notes meaningless, as EPA would determine whether 

1034 studies were required in private based on unspecified factors. EPA disagrees. The 

1035 commenters have misread the proposed rule language and misunderstood the purpose 

1036 for consultation. The consultation references were not intended to impose a mandatory 

1037 consultation requirement. To the contrary, the references to consultation waswere an 

1038 attempt by EPA to signal its willingness to meet with applicants to adapt studies, if 

1039 necessary, to the specifics of individual antimicrobials. 

1040 Consultation is a longstanding, commonly used and valuable process in EPA’s 

1041 Pesticide Program. Applicants often meet with OPP staff on a pre-submission basis to 

1042 review and discuss the adequacy of the available data. OPP believes that such 

1043 meetings are beneficial to both EPA and the applicants. In practice, such meetings are 

1044 very often sought by registrants and applicants. By encouraging communication and 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 43 of 233 

1045 exchange of ideas, such discussions can help in the development of clearer 

1046 expectations of what must be submitted in instances where data requirements involve 

1047 complexities. Consultation can result in data that better meets EPA’s needs and saves 

1048 resources for both EPA and the applicant. Depending upon what is intended to be 

1049 addressed, such meetings do not necessarily need to be held in person, but can be 

1050 frequently accomplished via tele-conferencing. 

1051 EPA did not intend its references to consultations in the test notes to impose 

1052 mandatory consultation requirements; neither did EPA intend the consultation 

1053 references as a means of establishing a different standard for determining if a study is 

1054 triggered. EPA has carefully reviewed all test notes in the antimicrobials final rule and 

1055 removed all references to consultation from all testnotestest notes for the antimicrobials 

1056 rule so there can be no chance of misunderstanding the voluntary nature of 

1057 consultation. 

1058 3. Comment on use of data in risk assessment. The commenters also argued 

1059 that reproposal was necessary because they could not meaningfully comment on the 

1060 proposal without understanding how the data would be used by EPA. Specifically, one 

1061 commenter wrote: “It is not plausible for [the commenter] or others to meaningfully 

1062 comment on the Proposal without the benefit of understanding the risk assessment 

1063 approaches EPA plans to use, (e.g., human and ecological), the ways in which the data 

1064 requirements will provide information to conduct those assessments and the ways EPA 

1065 will use those risk assessments in making regulatory decisions. 

1066 4. EPA’s response on use of data in risk assessment. EPA disagrees with this 

1067 comment for several reasons. First, how EPA conducts risk assessments and how it 

1068 uses toxicological, ecological, and exposure data in those risk assessments is well 

1069 known. Risk assessment is not unique to OPP. The principles used by OPP and, in 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 44 of 233 

1070 fact, by EPA are those used by the scientific community in general. OPP follows the 

1071 processes and procedures in the many risk assessment guidance documents that have 

1072 been issued by EPA (see http://www.epa.gov/riskassessment/guidance.htm). The 

1073 Agency’s exposure and risk assessment procedures have been presented in numerous 

1074 exposure and risk assessments for antimicrobial pesticides. EPA’s assessments reflect 

1075 the best available data, and the state of the science of exposure and risk assessment 

1076 models, methods, and procedures. 

1077 Moreover, OPP’s risk assessment procedures for pesticides are well1078 documented. EPA has recently concluded the process of completing Reregistration 

1079 Eligibility Decision Documents for all pesticides under FIFRA and reassessing all 

1080 FFDCA pesticide tolerances. This was a very open process involving multiple public 

1081 comment opportunities as to each pesticide. Further, all regulatory decision documents 

1082 as well as the underlying risk assessments have been made available to the public. 

1083 EPA has now begun new pesticide reviews under the Registration Review program, and 

1084 that process is equally open and transparent. 

1085 A second reason why EPA believes this comment to be misdirected is that the 

1086 proposed rule does not represent a change to EPA’s existing and transparent risk 

1087 assessment procedures. Rather, the proposal is merely designed to tailor the existing 

1088 data requirements that apply to all pesticides in a way that is more specific to 

1089 antimicrobial pesticides, as well as including some new requirements applicable to 

1090 antimicrobials. 

1091 Finally, the comment is without foundation because EPA has explained the need 

1092 for each study and provided background information on the purpose for which each 

1093 study would be required. Part 158, subpart B contains an extensive description of the 

1094 need for and use of submitted studies (40 CFR 158.130). Additionally, as explained in 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 45 of 233 

1095 the preamble to the antimicrobials proposed rule, EPA relied on the proposed and final 

1096 rules for establishing data requirements for conventional pesticides. As stated in the 

1097 proposed rule for antimicrobials, the rationales for requiring and/or revising particular 

1098 data requirements were in those rules. 

1099 With few exceptions, these rationales are also applicable to 

1100 antimicrobial pesticide chemicals, and as such have not been 

1101 repeated in today’s proposed rule. Today’s proposal discusses in 

1102 detail only those revisions that are singularly applicable to 

1103 antimicrobial pesticides, including antifoulants and wood 

1104 preservatives.” (73 FR 59384)). 

1105 

1106 Examples of studies applicable to antimicrobial pesticides and for which a 

1107 description of the need for the requirement was included in the preamble to the 

1108 proposed rule for antimicrobials include the need for: 

1109  The 90-day dermal and 90-day inhalation studies for a heating, ventilation, air 

1110 conditioning, and refrigeration uses ( 73 FR 59395), 

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

1112  Environmental fate studies to support a down -the -drain assessment (73 FR 

1113 59408). 

1114 One commenter presented several examples of what the commenter labeled as 

1115 EPA’s “ad hoc risk assessment processes.” An examination of those examples shows 

1116 that the commenter is concerned with what it labels as “inconsistency in EPA’s current 

1117 practice” as to when a dietary risk assessment is needed for antimicrobial pesticides. 

1118 The commenter argued that this alleged inconsistent practice shows the “need for 

1119 stable, transparent guidance on risk assessment to support data requirements 

1120 regulation.” EPA does not believe that it has been inconsistent in its risk assessments. 

1121 Furthermore, EPA does not believe that such “inconsistencies,” if they exist, would 

1122 mean that affected parties could not comment meaningfully on the proposed data 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 46 of 233 

1123 requirements. Ultimately, the issue with the data requirements rule is whether EPA has 

1124 asked for data needed for determining whether pesticides meet the relevant statutory 

1125 safety standards. The fact that EPA might have been inconsistent in the past in its 

1126 determinations with regard to the safety standard or how it went about assessing 

1127 whether a pesticide met the safety standards (e.g., did EPA need to do a dietary risk 

1128 assessment), does not handicap an affected party in determining whether a proposed 

1129 data requirement is consistent with the statutory safety standards. To reiterate, the 

1130 relevant question is not whether EPA has guidance on when dietary risk assessment is 

1131 needed but whether the proposed data requirements pertaining to dietary risk would 

1132 require information that are appropriate to EPA’s determination under the applicable 

1133 statutory safety standards. To the extent, the commenter is concerned with any 

1134 particular Agency decision regarding when a dietary risk assessment is needed for 

1135 antimicrobials, EPA encourages the commenter to raise that concern directly with the 

1136 Agency in the context of the specific matter causing the commenter concern. 

1137 This commenter later filed additional comments that further developed the 

1138 argument that reproposal is necessary because EPA allegedly has not clearly defined 

1139 when a dietary risk assessment is needed. The commenter wrote: “[T]he Proposal 

1140 does not clearly articulate any standards for determining what uses triggers a food 

1141 analysis. It has become apparent since the Proposal was issued that the Agency will 

1142 interpret this regulation to vastly increase the number of antimicrobials regulated as 

1143 food use.” (ACC/CSPA letter, identified in the docket at ;by document ID number EPA1144 HQ-OPP.-2008-0110-0107, p. 2). Further, the commenter then asserts that “EPA’s 

1145 economic analysis does not even attempt to address the increase in the burden on 

1146 registrants and applicants that this [alleged] expansion of the need for ‘food contact’ 

1147 approvals will cause.” (Id.) These additional comments suggest that this commenter is 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 47 of 233 

1148 concerned with EPA decisions issued prior to today’sthis final rule (and, in most cases, 

1149 prior to issuance of the proposed rule) and fears how the final rule may be interpreted in 

1150 the future. However, it is difficult to determine from these comments whether the 

1151 commenter is claiming that this alleged “expansion” of food use antimicrobials is 

1152 effected by any particular language in the proposed rule. To the extent the commenter 

1153 is arguing that the expansion is caused by EPA’s application of the FFDCA section 408 

1154 standard to all antimicrobial food uses under FIFRA section 2(bb) (whether the use 

1155 requires clearance under FFDCA section 408 or 409), the commenter, as explained in 

1156 Unit XVI.A,., misunderstands EPA’s authority under FIFRA and EPA’s practice as to 

1157 antimicrobials since the passage of ARTCA. In another place in its recently1158 filedsubsequent comments, the commenter argues that the use of the categories of 

1159 “direct food use” and “indirect food use” “creates the potential for almost all 

1160 antimicrobials to be considered as possibly leaving residues on food.” (ACC attachment 

1161 1, identified in the docket at ;by document ID number EPA-HQ-OPP.2008-0110-0108, p. 

1162 4)). However, EPA adopted the categories of direct and indirect food use as a way to 

1163 tier data requirements for residue chemistry and toxicology, not to expand the category 

1164 of food uses. For a use to qualify as an indirect food use it must result in residues in 

1165 food and EPA clearly has the authority under FIFRA and the FFDCA to request data on 

1166 and assess the risk of pesticide residues in food. Despite the commenter’s claims to 

1167 the contrary, it is not EPA’s intent to use this data requirements rule as a basis for 

1168 expanding what antimicrobial uses qualify as direct or indirect food uses. Accordingly, 

1169 EPA’s economic analysis has accurately captured the costs imposed by this rule. 

1170 5. Comment on lack of final guidelines. Finally, commenters argued that 

1171 reproposal was needed because affected parties cannot properly evaluate the data 

1172 requirements without final guidelines on how such studies should be conducted. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 48 of 233 

1173 6. EPA’s response on lack of final guidelines. EPA disagrees with this comment: 

1174 EPA can require submission of a particular study even if no guideline has been 

1175 provided. The types of data needed for EPA to make a registration decision are clearly 

1176 identified in its proposed rule. Testing laboratories routinely conduct these studies, as 

1177 evidenced by the test cost data which was available for use in both EPA’s and the 

1178 commenter’s economic analyses. Final guidelines are available for the majority of tests 

1179 required, and draft guidelines provide information for the applicant to consider. Since 

1180 there was an understanding of the types of data EPA proposed to require, the 

1181 commenter had sufficient information to comment on whether EPA had asked for the 

1182 data needed for determining whether pesticides meet the relevant statutory safety 

1183 standards. 

1184 It is important to keep in mind that, as noted in the proposed rule, new part 158, 

1185 subpart W is “retaining most current data requirements for antimicrobials. . . and revises 

1186 other existing data requirements.” (73 FR 59383) The guidelines that the commenter 

1187 asserts as not providing sufficient information to permit meaningful comment pertain, for 

1188 the most part, to these existing data requirements that are not being modified by this 

1189 rulemaking. As to the “new” data requirements that are imposed by this rule, the 

1190 commenter has not specifically explained why interested parties cannot meaningfully 

1191 comment on these requirements or why a final guideline is needed to provide 

1192 meaningful comments on these studies. In fact, as to these “new” studies, OPPTS 

1193 guidelines are available for all except the nature of the residue on surfaces study. For 

1194 that study, due to the many site- and chemical specific variations, a protocol review is 

1195 required. 

1196 This commenter later filed additional comments stating that “FIFRA requires EPA 

1197 to issue test guidelines.” (ACC/CSPA letter, identified in the docket at ;by document ID 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 49 of 233 

1198 number EPA-HQ-OPP.2008-0110-0107, p. 4). In accordance with FIFRA section 

1199 3(c)(2)(A), EPA has promulgated data requirement rules “specifying the kinds of 

1200 information which will be required to support the registration of a pesticide.” EPA is not 

1201 required to issue guidance explaining how studies that are addressing the data required 

1202 under the regulations should be performed. Additional information on EPA’s 

1203 development of guidelines is in Unit XX. 

1204 C. Alternative Testing Paradigms. 

1205 1. Comment. A commenter asked how OPP plans to implement the National 

Academy of Sciences (NAS)/EPA Vision of Toxicity Testing in the 21st 1206 Century or the 

1207 Strategic Plan for Evaluating the Toxicity of Chemicals. The commenter noted that the 

1208 rule should be specific in identifying alternative approaches that EPA will consider. 

1209 2. EPA’s Response. In the proposed rule, in Unit XVIII, entitled “Alternative 

1210 Testing Paradigms,” EPA discussed its commitment to moving towards a more efficient 

1211 and refined testing/risk assessment paradigm for antimicrobial pesticide chemicals. That 

1212 discussion included the following: 

1213  OPP’s current thinking on how Structure-Activity-Relationships (SAR) and 

1214 Quantitative SAR (QSAR or (Q)SAR) modeling could be used as part of an integrated 

1215 approach to hazard and risk assessment to support a regulatory decision-making 

1216 process for antimicrobial pesticides. 

1217  The evolution of the current paradigm of animal (in vivo) toxicity testing 

1218 toward a more integrated tiered testing approach for antimicrobial pesticides. 

1219  Development of computational tools for interpreting data from computational 

1220 chemistry, high-throughput screening (HTS) and genomic technologies. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 50 of 233 

1221  The EPA-funded reports by the NAS entitled “Toxicity Testing for Assessment 

of Environmental Agents” (2006) and “Toxicity Testing in the 21st 1222 Century: A Vision and 

1223 a Strategy” (2007). 

1224 The NAS recommendations are truly visionary and involve a transformative 

1225 paradigm shift in toxicology based largely on the increased use of in vitro molecular and 

1226 cellular assays, and computational modeling that make testing faster and less costly, 

1227 and reduces animal testing significantly. The new technologies are expected to help 

1228 EPA better understand how chemicals perturb normal biological function(s), and thus 

1229 identify toxicity pathways. Potential toxic effects of chemicals could then be predicted 

1230 based on in vitro bioactivity profiles derived from a chemical’s effects on cellular 

1231 molecules and processes. Thus, the scientific foundation for this new paradigm is 

1232 based on linking in vitro effects with adverse outcomes in vivo, and on computer 

1233 modeling that extrapolates to predicted responses in whole tissues, organisms and 

1234 populations based on realistic human or environmental exposures. 

1235 EPA is working to develop and evaluate new technologies in molecular, cellular, 

1236 and computational sciences to supplement or replace the more traditional methods of 

1237 toxicity testing and risk assessment (see http://www.epa.gov/pesticides/science/testing1238 assessment.html). Such an approach begins with consideration of exposure information 

1239 along with hazard-based hypotheses about the plausible toxicological potential of a 

1240 chemical or group of chemicals based on their physical-chemical properties and their 

1241 effects on biological targets in vitro. This information is then combined with computer 

1242 modeling to target animal testing to the specific data needed for human health and 

1243 ecological risk assessments. 

1244 No single new technology will be able to address all situations. However, by 

1245 using a suite of tools and approaches in combination, EPA believes it is possible to 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 51 of 233 

1246 improve the hazard and exposure assessments that form the basis for understanding 

1247 pesticide chemical risks. It will take time and substantial research to build this new 

1248 approach. OPP will incorporate the new technologies into EPA’s hazard and risk 

1249 assessment processes as the technologies are sufficiently developed and peer 

1250 reviewed. Development and vetting of this new approach to chemical management 

1251 must be accomplished while continuing to make pesticide registration decisions. 

1252 Eventually, the new technologies should: 

1253  Create a broader suite of computer-aided methods to better predict potential 

1254 hazards and exposures, and to focus testing on likely risks of concern. 

1255  Improve the approaches to more traditional toxicity tests to minimize the 

1256 number of animals used while expanding the amount of information obtained. 

1257  Improve OPP’s understanding of toxicity pathways to allow development of 

1258 non-animal tests that better predict how exposures relate to adverse effects. 

1259  Improve the diagnostic biomonitoring and surveillance methods to detect 

1260 chemical exposures and identify causes of toxic effects. 

1261 Since the publication of the proposed rule in October 2008, OPP announced its 

1262 strategic direction to move toward an improved testing and assessment paradigm where 

1263 in vivo (animal) testing would be targeted to the most likely hazards of concern. OPP 

1264 envisions an enhanced testing/assessment paradigm that is a progressive, tiered1265 testing approach. This paradigm shift should accrue the following benefits to OPP: 

1266  Ability to evaluate more chemicals across a broader range of potential effects 

1267 in a shorter time frame. 

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

1269  Enhanced predictive ability to determine whether animal testing is needed to 

1270 refine a risk assessment and to inform management decisions. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 52 of 233 

1271  Refine and reduce animal testing by maximizing information obtained from 

1272 animal studies, and focusing on effects of concern. 

1273  Opportunities for improved diagnostic biomonitoring and surveillance methods 

1274 to detect chemical exposures and identify causes of toxic effects. 

1275  Enhance the quality and efficiency of risk assessment and risk management 

1276 decisions. 

1277 Over the next several years, OPP intends to improve and transform its approach 

1278 to pesticide risk management by enhancing its ability to use integrated approaches to 

1279 testing and assessment. The Agency’s work on an integrated approach means the 

1280 development of increasingly effective laboratory animal tests that are designed to 

1281 maximize the information generated about the nature of the effects being studied. OPP 

1282 intends to expand its toolbox of predictive models. The new toxicity and exposure 

1283 approaches will enhance priority-setting and screening approaches and therefore focus 

1284 Agency and societal resources on those chemicals with the greatest risk potential. 

1285 These advances will be incorporated within a risk assessment framework of 

1286 problem formulation, hazard, dose response, exposure assessment, and risk 

1287 characterization to support pesticide registration decisions. As this framework evolves, 

1288 EPA will create pilot programs and develop guidance documents to inform applicants 

1289 and others of the alternative approaches being used. 

1290 It will require many years to realize the NAS vision of a new toxicity paradigm 

1291 based on evaluating perturbations in cellular pathways by reliance on an array of 

1292 computational and in vitro methods. However, the development and expansion of 

1293 certain tools used to guide more intelligent in vivo testing is anticipated to become 

1294 available in the nearer term (≤5 years) which includes (Q)SAR/expert systems, TTCs, 

1295 and in vitro technologies. As EPA transitions to the use of these components of 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 53 of 233 

1296 intelligent testing or alternative methods, communication will be essential. Through its 

Pesticide Program Dialog Committee, OPP has created a 21st 1297 Century Toxicology/New 

1298 Integrated Testing Strategies Workgroup. For information, see 

1299 http://www.epa.gov/pesticides/ppdc/testing/index.html. 

1300 Additionally, OPP has and will continue to publicly vet this new approach. On 

1301 May 24 – 26, 2011, OPP requested that the FIFRA Scientific Advisory Panel (SAP) 

1302 consider and revise a set of scientific issues related to Integrated Approaches to Testing 

1303 and Assessment (IATA) Strategies: Use of new computational and molecular tools. 

1304 OPP plans to build on an established foundation of using a variety of tools in a tiered 

1305 testing and assessment framework by systematically adding new tools and 

1306 methodologies, as well as an advancing understanding of key events in toxicity 

1307 pathways. OPP requested the SAP's input on EPA’s plans to maximize use of existing 

1308 data from similar compounds, including information from new toxicity hazard 

1309 computational and in vitro predictive models, and exposure modeling to target in vivo

1310 toxicity testing that is necessary to assess and manage chemical risks, appropriately. 

1311 Two case studies illustrated the use of these approaches. The SAP Report, once 

1312 completed, will be is available at 

1313 http://www.epa.gov/scipoly/sap/meetings/2011/052411meeting.html#frn.

1314 VI. Discussion of Key Comments on Antimicrobial Use Patterns

1315 A. Definitions of Use Patterns 

1316 1. Comment. The commenter suggested different use patterns for EPA to 

1317 consider. The commenter believes that the use patterns proposed by EPA are not use 

1318 patterns but descriptions of product types. The commenter suggested six general use 

1319 patterns for EPA to consider. These include: 

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

Page 54 of 233 

1321  Indoor residential/commercial/institutional nonfood; 

1322  Indoor commercial/institutional food; 

1323  Aquatic areas nonfood; 

1324  Aquatic areas food; 

1325  Material preservative for exempt treated article uses. 

1326 2. EPA’s response. The Agency disagrees that these suggested use patterns 

1327 are adequate substitutes for the proposed use patterns. The use patterns that EPA 

1328 proposed provide a reasonable approach for allowing the Agency to more clearly 

1329 identify and tailor the data requirements for the different type of antimicrobial pesticides. 

1330 In some cases, that is best accomplished by using the product type to define the use 

1331 pattern. 

1332 EPA has reviewed the commenters’ descriptions of their six suggested general 

1333 use patterns and has determined that they do not acknowledge all potential exposure 

1334 pathways of antimicrobial pesticides, particularly those discharged to wastewater as a 

1335 result of processing and end-use. Although three of the proposed general use patterns 

1336 include “indoor” in the name, the exposure potential for these use patterns is not limited 

1337 to the indoor environment. This is because these patterns include processes and end1338 uses of antimicrobial pesticides that are discharged to wastewater, thereby leading to 

1339 the potential for microorganisms in WWTPs to be exposed to antimicrobial pesticides 

1340 and for aquatic organisms to be exposed to antimicrobial pesticides in surface water 

1341 downstream of WWTPs. If the antimicrobial is not completely removed during 

1342 treatment, exposures of humans to antimicrobials may also be associated with 

1343 antimicrobials discharged to wastewater that enters WWTPs and subsequently enters 

1344 surface water via WWTP effluents. Furthermore, there may also be the potential for 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 55 of 233 

1345 terrestrial organisms and humans to be exposed to antimicrobial pesticides if the 

1346 antimicrobial that is discharged to wastewater partitions to biosolids. 

1347 Since the processing or end-use of an antimicrobial pesticide in an indoor setting 

1348 does not preclude the potential for its release to ambient environmental media, 

1349 particularly under circumstances in which there is potential for discharges of 

1350 antimicrobial pesticides to wastewater, EPA believes that the designation of an 

1351 antimicrobial use patterns as “indoor” is misleading. Based on the conclusion that 

1352 processing or end-use of an antimicrobial pesticide in an indoor setting does not 

1353 preclude its release to the ambient environment, EPA believes that a down -the -drain 

1354 analysis is needed for all use patterns with the exception of the aquatic areas use 

1355 pattern. 

1356 The commenter’s suggested use patterns are also inconsistent with EPA’s 

1357 reevaluationre-evaluation of the data required for wood preservatives. In response to 

1358 comments, the Agency determined that all treated wood needs to be considered as 

1359 having the potential to come into contact with surface water. Therefore, for wood 

1360 preservatives, EPA has changed several data requirements in both the environmental 

1361 fate table and the non-target organisms table from “CR” to “R.” However, under the 

1362 commenter’s six suggested use patterns, wood preservatives would be considered to 

1363 be the same as material preservatives: The commenter did not differentiate the data 

1364 needed between the two use patterns. EPA believes that the data needed for a wood 

1365 preservative is distinctly different from that needed for a materials preservative. Wood 

1366 preservatives have a high potential for environmental exposure, as evidenced by both 

1367 environmental fate and nontarget organisms data requirements that are “R.” Material 

1368 preservatives have a lower potential for environmental exposure and consequently are 

1369 “CR.” Thus, the data requirements codified todayin this final rule acknowledge the 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 56 of 233 

1370 differences in the data needed by having two distinctly different use patterns: Wood 

1371 preservatives and material preservatives. 

1372 Given the inclusion of the term “indoor” as part of the title of three of the 

1373 suggested use patterns, and the combining of wood preservatives and materials 

1374 preservatives into a single use pattern, EPA believes that the six general use patterns 

1375 suggested by the commenter (see above) would not adequately serve EPA’s or the 

1376 public’s needs. Additionally, the 1997 review by the FIFRA Scientific Advisory Panel 

1377 (SAP) of EPA’s 12 antimicrobial use patterns indicated the SAP’s agreement that the 

1378 Agency’s proposed designation of 12 use patterns was a reasonable approach to 

1379 organizing data requirements, and was, in fact, similar to the approaches used by 

1380 Canada’s Pest Management Regulatory Agency (PMRA), and the California 

1381 EPA.Environmental Protection Agency. Therefore, EPA is codifying the 12 use patterns 

1382 that were proposed. 

1383 B. Wood Preservative Use Pattern

1384 1. Comment. Several commenters questioned how wood preservatives were 

1385 treated in the proposed rule. One commenter thought that all wood preservatives 

1386 should be considered as having contact with water. Another commenter argued that the 

1387 industrial, commercial and do-it-yourself uses of wood preservatives are different and 

1388 should be assessed differently. 

1389 2. EPA’s response. Wood preservatives are pesticides for incorporation into 

1390 wood products to control wood degradation problems due to fungal rot or decay, 

1391 sapstain, molds, or wood-destroying insects. 

1392 As explained in the proposed rule, (73 FR 59405) EPA’s current practice of 

1393 determining the data required for a wood preservative product is dependent upon where 

1394 the product is intended to be used (land-only versus land and aquatic). Under this 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 57 of 233 

1395 approach, fewer environmental fate and ecological effects studies are required for 

1396 products that limit their use patterns to land-only uses. This approach also assumes 

1397 that diversion does not occur and that wood that is treated for land-only uses does not 

1398 end up in the water and vice versa. EPA specifically requested comments on the 

1399 regulation of wood preservative products, and indicated that based on the comments 

1400 received could determine to continue with the current practice of considering land-only 

1401 applications, or change to a land and aquatic usage. Based on comments indicating 

1402 that the data required to register a wood preservative should not differentiate between 

1403 land only and aquatic only applications of treated wood, EPA has re-evaluated this 

1404 approach. As discussed in the proposed rule, it is difficult to assure that diversion does 

1405 not occur. EPA considered three possibilities: 

1406  Assume all treated wood could have the potential to come into contact with 

1407 surface water. 

1408  Use an approach similar to that advocated by the American Wood Protection 

1409 Association (AWPA) approach which differentiates between marine/freshwater and 

1410 ground contact use/above ground contact use. 

1411  Maintain status-quo. 

1412 Wood preservatives used to protect wood structures placed directly in or over 

1413 water (e.g., marine pilings, docks) will leach active ingredient into the water, resulting in 

1414 potential exposure of aquatic organisms. Wood preservatives used in the terrestrial 

1415 environment for uses such as fences, siding, and decks will leach active ingredient into 

1416 soil where it may be transported into the aquatic environment and expose aquatic 

1417 organisms. 

1418 The Emission Scenario Document (ESD) for Wood Preservatives prepared by 

1419 the Organization for Economic Co-operation and Development (OECD) as part of its 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 58 of 233 

1420 Series on Emissions Scenario Documents provides guidance on how to estimate 

1421 emissions of chemical substances in wood preservative products to air, water, and soil 

1422 as a result both of product application and storage of treated wood prior to shipment 

1423 and treated wood-in-service. This OECD ESD documents the occurrence of pathways 

1424 of release of chemical substances during wood preservative application to facility drains 

1425 that subsequently convey wastewater to WWTPs; entry of chemical substances to 

1426 adjacent surface water bodies by way of run-off water from unpaved storage of wood 

1427 preservative-treated products following a rain event; and leaching of chemical 

1428 substances from in-service uses of treated exterior wood out of ground (i.e., fences, 

1429 noise barriers), wood in-ground (transmission poles, fence posts), and wood in direct 

1430 contact with fresh and sea water (poles and planks/decking of jetties and wharfs). 

1431 Additional information on indirect releases to surface water of antimicrobial pesticides 

1432 used as wood preservatives can be found in response to comment 134.1 in the 

1433 Response to Comments Document in the docket at http://www.regulations.gov. 

1434 Given the number of pathways identified, that result in potential exposure from 

1435 treated wood, the Agency determined that all treated wood should be considered as 

1436 having the potential to come into contact with surface water. All wood preservative risk 

1437 assessments will now be performed considering that the treated wood could end-up 

1438 either on the land or in the aquatic environment. As previously discussed, there are 

1439 multiple pathways for wood preservative degradates and/or leachates to reach surface 

1440 water. The AWPA approach would have continued the practice of determining the data 

1441 requirements based on the intended use site of the treated product. 

1442 Given this decision, that all treated wood could have the potential to come into 

1443 contact with surface water, the wood preservative columns of the final Environmental 

1444 Fate and the Nontarget Organisms Tables were revised. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 59 of 233 

1445 For the final Environmental Fate Table, for the wood preservatives column, the 

1446 data requirements for anaerobic soil metabolism, aerobic aquatic metabolism, and 

1447 anaerobic aquatic metabolism were changed from “CR” to “R.” Because treated wood 

1448 products have outdoor usages, the Agency believes that these products have the 

1449 potential to come into contact with surface water as well as soils which can become 

1450 flooded or waterlogged and then be released to surface water. 

1451 For the final Nontarget Organism Table, for the wood preservatives column, the 

1452 data requirements for chronic toxicity testing with fish (fish early-life stage) and aquatic 

1453 invertebrate (aquatic invertebrate life-cycle) are being changed from “CR” to “R” to 

1454 provide chronic data when chronic exposure is expected. 

1455 The Agency agrees that the industrial, commercial, and do-it-yourself uses of 

1456 wood preservatives are different in terms of human exposure. Industrial wood 

1457 preservative uses are assessed for those workers involved in the actual treatment of the 

1458 wood with the preservative. This includes operations at a pressure treatment facility 

1459 where workers add the preservative to treatment cylinders, remove treated wood 

1460 charges from the cylinders, check the treated wood to verify retention rates, and move 

1461 the freshly treated wood around the facility (from cylinder to drip pad to storage to 

1462 shipping). Industrial sapstain wood preservatives are also assessed at the treatment 

1463 facility for the application of the pesticide. Worker tasks for the non-pressure treatment 

1464 (non-PT) are slightly different than those at pressure treatment (PT) facilities. Separate 

1465 exposure measurements unique to each type of treatment (PT vs non-PT) are used in 

1466 the assessments. 

1467 Exposures to commercial and do-it-yourself uses of treated wood are assessed 

1468 for those installing the treated wood and for those exposed to the treated structures 

1469 (e.g., play sets and decks). 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 60 of 233 

1470 VII. Discussion of Key Comments on General and Administrative Issues 

1471 A. Scientific Advisory Panel (SAP) Waivers 

1472 1. Comment. A commenter noted that in the preamble to proposed part 158, 

1473 subpart W, EPA cites multiple SAP reports that did not specifically mention antimicrobial 

1474 pesticides. Therefore, the commenter believes these SAP reviews were insufficient. 

1475 Another commenter noted that it has been 9 years since the last SAP review and that 

1476 EPA should request another SAP review prior to implementation of proposed part 158, 

1477 subpart W. Still another commenter believes that EPA’s request that the SAP waive its 

1478 review of proposed part 158, subpart W based on the SAP’s 1997 review was improper, 

1479 and that the SAP cannot waive its statutory review obligation.

1480 2. EPA’s response. EPA disagrees with the comments. On June 3, 1997, EPA 

1481 presented an early version of the part 158, subpart W proposal in an open meeting to 

1482 the SAP. At that time, the SAP provided extensive comments in five areas: Toxicology, 

1483 residue chemistry, ecological effects and environmental fate, human exposure, and 

1484 efficacy. Since then, the SAP has considered many specific studies and scientific issues 

1485 included in proposed part 158, subpart W as part of their reviews of guidelines and of 

1486 data requirements for conventional agricultural pesticides (see references 30, 31, 32, 

1487 33, and 34 to the proposed rule).the documents identified in the docket by document ID 

1488 numbers EPA-HQ-OPP-2008-0110-0032, -0033, -0034, -0035, and -0036). In 1997, the 

1489 SAP also noted its concern about the possible effects of antimicrobials on WWTPs. 

1490 Partially in response to the SAP comments, EPA proposed a tiered set of environmental 

1491 fate data requirements that will allow the Agency to better characterize potential 

1492 incidences of antimicrobials in surface waters, as a result of down -the -drain uses of 

1493 antimicrobials. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 61 of 233 

1494 When the Agency prepared to propose 40 CFR part 158, subpart W, EPA 

1495 requested that the SAP waive its review of the about-to-be-proposed part 158, subpart 

1496 W because there were no new scientific issues. The SAP waived its review of the 

1497 about-to-be proposed part 158, subpart W on February 19, 2008. The Agency 

1498 continues to believe that there are no new scientific issues that warrant additional 

1499 review by the SAP. EPA’s request for ana SAP waiver for the final antimicrobial data 

1500 requirements rule is discussed in Unit XXIV. FIFRA section 25 requires EPA to give the 

1501 SAP at least 60 days to review proposed regulations and 30 days to review final 

1502 regulations. However, the SAP can determine to waive its review during the statutory 

1503 time periods. 

1504 B. Risk Assessments for Wood Preservatives. 

1505 1. Comment. A commenter noted that Canada’s PMRA and USEPA conduct risk 

1506 assessment for wood preservatives differently. EPA’s risk assessment is based on the 

1507 treated wood when used at the final use site, while the PMRA’s risk assessment is 

1508 based at the site where the wood is treated. The PMRA also does not distinguish 

1509 between terrestrial-only or aquatic-only use for anti-sapstains and heavy-duty wood 

1510 preservatives. 

1511 2. EPA’s response. The Agency acknowledges differences between its risk 

1512 assessment of wood preservatives and that of Canada’s PMRA. As previously 

1513 discussed in Unit VI.A,., EPA has re-evaluated its approach for determining the data 

1514 required for a wood preservative product. As part of the re-evaluation, EPA considered 

1515 the human and ecological risks based on exposure pathways identified in OECD’s ESD 

1516 for Wood Preservatives. This ESD identifies potential human and ecological exposures 

1517 from both treatment of wood at processing facilities and in-service uses on land and in 

1518 water. The Agency determined that all treated wood should be considered as having 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 62 of 233 

1519 the potential to come into contact with surface water. This determination reflects EPA’s 

1520 concern about the potential for the indirect release to surface waters of wood 

1521 preservatives. As a result, EPA is changing its approach to requiring environmental and 

1522 ecological effects studies for wood preservatives. All wood preservative risk 

1523 assessments will now be performed considering that the treated wood could end-up 

1524 either on the land or in the aquatic environment, thus increasing harmonization between 

1525 PMRA and EPA with regard to wood preservatives. 

1526 D.C. Clarity on How and When CR Data is Required 

1527 1. Comment. A commenter asked EPA to specify criteria to determine whether 

1528 a data requirement is “R” (Required) or “CR” (Conditionally Required). According to the 

1529 commenter, the discussion of “R” and “CR” suggests that a data requirement labeled 

1530 “CR” may not be required to be addressed by the applicant. A second commenter 

1531 stated that it is unclear how and when conditionally required data are triggered. Another 

1532 commenter asserted that data requirements should be waived only under extraordinary 

1533 circumstances, and that the use of waivers can effectively preclude appropriate 

1534 regulation of the pesticide under FIFRA. 

1535 2. EPA’s response. In its proposed data requirement tables, EPA specified 

1536 whether a data requirement is “Required”, “Conditionally Required”, or “Not Required” 

1537 based on how likely the study is needed to complete an assessment of an antimicrobial 

1538 pesticide. As a rule of thumb, a “required” study is likely to be needed 50 percent of the 

1539 time or more and a “conditionally required” study is likely to be needed less than 50 

1540 percent of the time. Typically, a “conditionally required” study is triggered based on the 

1541 results of a study that has already been conducted. Triggers in the test notes indicate 

1542 the circumstances under which the Agency has learned through experience that the 

1543 information is needed. In many instances, the applicant would be able to make the 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 63 of 233 

1544 determination that the trigger has been met and should include the data in their original 

1545 submission. In other cases, EPA will make the determination based on its review of 

1546 submitted data and would then request additional data from the applicant. EPA 

1547 encourages applicants to consult with the Agency to determine the actual need for the 

1548 data. 

1549 All data requirements must be addressed by the applicant by either conducting 

1550 the study or submitting information that could fulfill the data requirement, such as citing 

1551 open literature or other data sources, or by requesting and receiving a data waiver. 

1552 EPA grants data waiver requests only on a case-by-case basis and only when the 

1553 available evidence indicates a particular study is not needed or that there are particular 

1554 reasons for not conducting the study. For example, if the physical/chemical properties 

1555 of the chemical did not lend themselves to the testing procedure, such as performing an 

1556 inhalation study with a chemical that is a solid and has an extremely low vapor 

1557 pressure, then a waiver might be granted. EPA also grants waivers in exceptional 

1558 circumstances, for instance, if a test substance is so corrosive that animal studies would 

1559 cause undue pain and suffering. 

1560 VIII. Discussion of Key Comments on Product Chemistry 

1561 The following represent the significant comments received on the need for and 

1562 evaluation of product chemistry studies as proposed by EPA. 

1563 A. Application of Subpart D Product Chemistry Data Requirements to Antimicrobials.

1564 1. Comment. A commenter requested that EPA provide adequate justification for 

1565 applying the existing product chemistry data requirements for conventional pesticides to 

1566 antimicrobials without consideration of the highly dissimilar chemistries and 

1567 inapplicability of many of the requirements. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 64 of 233 

1568 2. EPA’s response. It has been EPA’s longstanding practice to require product 

1569 chemistry data. Product chemistry data are required to identify the chemicals used to 

1570 manufacture a product and to understand the physical and chemical properties of the 

1571 ingredient or product. Such information is generally independent of the intended use 

1572 pattern. Product chemistry data are used during label development to identify 

1573 information to be included on the label, such as the flammability statement, and 

1574 directions for disposal of the product. Hence, despite any differences between 

1575 conventional and antimicrobial pesticides, the Agency believes it is appropriate to apply 

1576 the same product chemistry data requirements to antimicrobials as required for 

1577 conventional pesticides. The guidelines for conducting product chemistry studies offer 

1578 flexibility to account for differences between chemical classes. 

1579 B. Lack of Adequate Opportunity for Review of Product Chemistry Data Requirements 

1580 1. Comment. One commenter asserted that registrants of antimicrobial 

1581 pesticides were not given the opportunity to review and comment on conventional 

1582 pesticide data requirements that are now being proposed for antimicrobial pesticides. 

1583 2. EPA’s response. .In the preamble to proposed part 158, subpart W, EPA 

1584 proposed to apply the product chemistry data requirements for conventionals in 40 CFR 

1585 part 158 subpart D to antimicrobial pesticides. Therefore, during the public comment 

1586 period for the proposed part 158, subpart W, from October 8, 2008, to April 6, 2009, any 

1587 interested party could have commented on the product chemistry data requirements in 

1588 subpart D (which have been in place since October 2007) and their potential 

1589 applicability to antimicrobials. 

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

Page 65 of 233 

1591 The following represent the significant comments received on the need for and 

1592 evaluation of product performance studies as proposed by EPA. Changes from the 

1593 proposed rule to the final rule are also described.

1594 A. Product Performance Guidelines 

1595 1. Comment. Several commenters shared their belief that EPA was seeking to 

1596 avoid comment on the product performance data requirements in the proposed rule by 

1597 stating that the Agency” “is not proposing to revise product performance data 

1598 requirements” at this time. Another commenter asked how the product performance 

1599 section of the proposed rule could be finalized without the 810 guidelines? 

1600 2. EPA’s response. The proposed product performance data requirements table 

1601 containedreferenced the older 91 series guidelines. As stated in the proposed rule, the 

1602 requirements being proposed were “nearly identical” to the existing data requirements in 

1603 § 158.400 and 161.640, and the table was “transferred essentially unchanged” (73 FR 

1604 59391). Since the 2008 proposed rule, EPA published the draft 810 guidelines for 

1605 comment. four of the 810 series guidelines (810.2000, 810.2100, 810.2200, and 

1606 810.2300 for sterilants, disinfectants and sanitizers) were published for comment in the 

1607 Federal Register for public comment on of January 27, 2010 (75 FR 4308). 4380)

1608 (FRL 8437-2), indicating that these guidelines represent the Agency’s current 

1609 recommendations for conducting product performance studies to support antimicrobial 

1610 pesticide label claims. That Notice of Availability announced that the 810 guidelines 

1611 series would be incorporated into the final rule for antimicrobial data requirements

1612 regulation: As announced. Three additional product performance guidelines (810.2400, 

1613 810.2500, and 810.2600) published for public comment on September 15, 2011 (76 FR 

1614 57031) (FRL 8879-1). Thus, in addition to commenting on the draft guidelines 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 66 of 233 

1615 themselves, commenters had an opportunity to comment on the inclusion of the 810 

1616 series in the Product Performance Data Requirements table. 

1617 The availability of the final guidelines for sterilants, disinfectants and sanitizers 

1618 (810.2000, 810.2100, 810.2200, and 810.2300) was announced in the Federal 

1619 Register of March 16, 2012 (77 FR 15750) (FRL 9332–4), and for the three additional 

1620 product performance guidelines (810.2400, 810.2500, and 810.2600) in the Federal 

1621 Register of June 27, 2012 (77 FR 38280) (FRL 9349-5).

1622 In this final rule, EPA is replacing the 91 series designations proposed in the part 

1623 158, subpart W product performance table with the appropriate 810 series guideline 

1624 numbers and names. Thus, commenters had an opportunity to comment on the 

1625 inclusion of The 810 series in the final Product Performance Data Requirements table. 

1626 Three additionalguidelines represent the Agency’s current recommendations for 

1627 conducting product performance guidelines (810.2400, 810.2500, and 810.2600) should 

1628 be published for comment in a timeframe similar to that of publication of the final rule for 

1629 Antimicrobial Data Requirements.studies to support antimicrobial pesticide label claims. 

1630 See Unit XVIII. for a discussion on guidelines. 

1631 B. Emerging Pathogens

1632 1. Comment. A commenter asked why there is no formal regulatory practice for 

1633 registering products to address public health emergencies or emerging pathogens 

1634 promptly and effectively? 

1635 2. EPA’s response. EPA does not believe that the promulgation of a rule dealing 

1636 with data requirements is the appropriate place to address emerging pathogens. A 

1637 major consideration in the Agency's process for addressing public health emergencies 

1638 and emerging pathogens is to work closely with the Centers for Disease Control and 

1639 Prevention (CDC), Department of Agriculture (USDA),, and FDA, as appropriate, to 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 67 of 233 

1640 provide a timely and accurate response to these situations. Under FIFRA section 18, 

1641 the Agency also has authority to grant certain exemptions from the provisions of FIFRA 

1642 and also to approve the use of unregistered pesticides when emergency conditions 

1643 exist. Additionally, in April 2008, the Agency implemented a disinfection hierarchy 

1644 policy for addressing emerging viral pathogens. Information on this policy is available on 

1645 the EPA website at http://www.epa.gov/oppad001/disinfection_hier.htm. EPA believes 

1646 that emerging pathogens require flexibility and speed in disseminating information and 

1647 seeks to address such situations in a prompt and effective manner. 

1648 C. Definitions of Sanitizer and Disinfectant 

1649 1. Comment. Several commenters claimed that the proposed definitions do not 

1650 reflect the work done by the regulated community in cooperation with EPA since 1999. 

1651 In particular, these commenters did not agree with the proposed definitions of sanitizer 

1652 and disinfectant. 

1653 2. EPA’s response. Since the publication of the proposed rule, the definitions, 

1654 including those for sanitizer and disinfectant, were published in the Federal Register for 

1655 public comment on January 27, 2010, as part of requesting comment on draft guideline 

1656 810.2000. After further review of the comments submitted on the proposed definition for 

1657 disinfectant and sanitizer, the Agency has revised the definitions that had been 

1658 proposed for both part 158, subpart W and the 810 Guidelines. EPA believes that the 

1659 definitions being codified today in part 158, subpart W reflect the input received from the 

1660 regulated community in multiple submissions. The definitions for sanitizer and 

1661 disinfectant will be the same in both part 158, subpart W and in the 810 Guidelines.

1662 The definition for disinfectant is being revised from, “Disinfectant means a 

1663 substance, or mixture of substances that destroys or eliminates a specific species of 

1664 infectious or public health microorganism, but not necessarily bacterial spores, in the 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 68 of 233 

1665 inanimate environment” to read, “Disinfectant means a substance, or mixture of 

1666 substances, that destroys or irreversibly inactivates bacteria, fungi and viruses, but not 

1667 necessarily bacterial spores, in the inanimate environment.” 

1668 The definition for sanitizer is being revised from, “Sanitizer means a substance, 

1669 or mixture of substances that reduces the bacterial population in the inanimate 

1670 environment by significant numbers, but does not destroy or eliminate all bacteria or 

1671 other microorganisms” to read, “Sanitizer means a substance, or mixture of substances 

1672 that reduces the bacterial population in the inanimate environment by significant 

1673 numbers, (e.g., 3 log10 reduction) or more, but does not destroy or eliminate all bacteria. 

1674 Sanitizers meeting Public Health Ordinances are generally used on food contact 

1675 surfaces and are termed sanitizing rinses.” A 3 log10 reduction is the minimum log 

1676 reduction needed to make a non-food contact surface sanitizing label claim, and is 

1677 considered a significant reduction.

1678 The definitions for fungicide, sterilant, tuberculocide and virucide are being 

1679 revised to include the following phrase: “or mixture of substances.” Inclusion of this 

1680 phrase in all of the definitions in § 158.2203 for types of products that bear public health 

1681 claims (excepting microbiological water purifier) means consistency in the definitions 

1682 and an acknowledgement that the destroying, reducing, or inactivating may be 

1683 accomplished via more than a single substance. Also, this makes these definitions 

1684 similar to the FIFRA section 2(u) definition of pesticide which also contains the phrase 

1685 “or mixture of substances.” 

1686 Additionally, the definition for virucide is being revised to include the word 

1687 irreversibly, as follows: “Virucide means a substance, or mixture of substances, that 

1688 destroys or irreversibly inactivates viruses in the inanimate environment,” thus reading 

1689 similar to the definition for tuberculocide. Additionally, the definition for sterilant will be 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 69 of 233 

1690 revised to remove the second sentence of the proposed definition: “For purposes of this 

1691 subpart, ‘sporicide’ and ’sterilant’ are synonymous.” EPA no longer requires that 

1692 products that make sporicidal claims also make sterilant claims. 

1693 D. Nonpublic Health Data and Claims 

1694 1. Comment. A commenter asked that the issue of when to generate efficacy 

1695 data for nonpublic health products be discussed, since registrants are required to 

1696 develop data to substantiate label claims. 

1697 2. EPA’s response. The Agency believes this issue has been addressed in § 

1698 158.2220 "Product Performance," which clearly states, "Each applicant must ensure 

1699 through testing that his product is efficacious when used in accordance with label 

1700 directions and commonly accepted pest control practices.” However, to clarify the issue 

1701 further, the Agency is adding a definition for nonpublic health claims that will appear as 

1702 40 CFR 158.2204(b): 

1703 Nonpublic health claim. An antimicrobial pesticide is considered to 

1704 make a nonpublic health claim if the pesticide product bears a 

1705 claim to control microorganisms of economic or aesthetic 

1706 significance, where the presence of the microorganism would not 

1707 normally lead to infection or disease in humans. Examples of 

1708 nonpublic health claims include, but are not limited to, algaecides, 

1709 slimicides, preservatives and products for which a pesticidal claim 

1710 with respect to odor sources is made. 

1711 

1712 Additionally, EPA is revising 40 CFR 158.2220(c)(3) to read: 

1713 (3) Product performance data for each product that bears a 

1714 nonpublic health claim. Each product that bears a nonpublic 

1715 health claim, as described in §158.2204(b), must be supported by 

1716 product performance data. Each registrant must ensure through 

1717 testing that his product is efficacious when used in accordance 

1718 with label directions and commonly accepted practices. The 

1719 Agency reserves the right to require, on a case-by-case basis, 

1720 submission of product performance data for any pesticide product 

1721 registered or proposed for registration or amendment. 

1722 

1723 Also, EPA has posted on the Antimicrobials Division website the parts of the 91 

1724 Guideline series that apply to testing of nonpublic health products. Although these 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 70 of 233 

1725 guidelines are from 1982, they are still relied on to develop data to support label claims

1726 for nonpublic health label claimsproducts. EPA acknowledges that some of the 

1727 references in the 1982 guidelines are to the older 91 series guidelines, which is being 

1728 replaced by the 810 series guidelines. To assist readers, EPA has also posted a cross1729 walk table so readers can locate the applicable section of the 810 Guidelines. For 

1730 information, see http://www.epa.gov/oppad001/non-public-health.html.

1731 X. Discussion of Key Comments on Toxicology Data Requirements 

1732 The following represent the significant comments received on the need for and 

1733 evaluation of toxicology studies as proposed by EPA. Changes from the proposed rule 

1734 to the final rule are also described.

1735 A. TTCA. Threshold of Toxicological Concern Approach

1736 1. Comment. There should be a threshold of toxicological concern (TTC) type of 

1737 approach for antimicrobials. 

1738 2. EPA’s response. OPP’s Antimicrobials Division is aware of the TTC concept, 

1739 and in conjunction with. ILSI, is currently pursuing the development of an application of 

1740 the TTC concept to evaluate antimicrobial pesticides. At this time, EPA anticipates a 

1741 timeframe of 2 to 3 years for development. Once a TTC-based approach has been 

1742 developed and piloted, then EPA would consider when/if the approach should be 

1743 included in part 158, subpart W Development and peer review of a TTC approach for 

1744 antimicrobials is expected to occur over the next 1 to 2 years. Based on expert peer 

1745 review and public comment, the Agency will make decisions regarding implementation. 

1746 B. Test Note to Neurotoxicity Studies 

1747 1. Comment. A commenter stated that proposed test note 6 to the proposed 

1748 toxicology table in § 158.2230 triggering the neurotoxicity studies is contradictory and 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 71 of 233 

1749 unclear. The commenter asked how the absence of a neurotoxicity screen in the 90-

1750 day oral rodent study would impact proposed test note 6? 

1751 2. EPA’s Response. Proposed test note 6 specifies that if the neurotoxicity 

1752 screen that occurs in the 90-day oral rodent study or any other data demonstrate 

1753 neurotoxic effects, then both the acute neurotoxicity study and the 90-day neurotoxicity 

1754 study are triggered. For certain use patterns with the potential for larger exposures 

1755 (most notably food exposures), all three of these studies are initially required. 

1756 According to proposed test note 8 to the proposed toxicology table in § 158.2230, the 

1757 applicant may combine the 90-day oral toxicity study and the 90-day neurotoxicity study 

1758 by adding a separate group of test animals. 

1759 However, for some use patterns, the 90-day oral study is required, and the other 

1760 two studies are conditionally required, being triggered by proposed test note 6. EPA 

1761 acknowledges that when only the 90-day oral study is required, an applicant is at a 

1762 disadvantage in terms of any chance for combining the 90-day neurotoxicity study with 

1763 the oral study: Once the 90-day oral study with its neurotoxicity screen has been 

1764 performed, and neurotoxic effects are identified, then it is not possible to add a separate 

1765 group of test animals to the already conducted study. 

1766 As a point of clarification, EPA is adding a new test note to the final Toxicology 

1767 Table in § 158.2230(g) to clarify that the neurotoxicity screen that is part of the 90-day 

1768 oral study is not equivalent to a 90-day neurotoxicity study. If the 90-day oral toxicity 

1769 study does not have a neurotoxicity screen, then the acute neurotoxicity study in the rat 

1770 would be required. The new test note also includes: “if the 90-day oral rodent study 

1771 does not include a neurotoxicity screen, then the acute neurotoxicity study will be 

1772 required.” As part of renumbering, this new test note is now test note 11 to the 

1773 Toxicology Table in the final rule, § 158.2230(g).) in this final rule,.
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 72 of 233 

1774 C. End-Product Use-Dilution Toxicity Testing

1775 1. Comment. Several commenters stated their belief that acute end product 

1776 use-dilution toxicity testing should be optional and requested greater clarification on 

1777 when to test a diluted product. The commenters asked whether extrapolation from the 

1778 active ingredient or as-sold acute toxicity testing is acceptable? Another commenter 

1779 claimed that requiring end-product six-pack testing of one or more dilutions is 

1780 duplicative. 

1781 2. EPA’s response. Proposed test note 2 to the proposed toxicology table in § 

1782 158.2230, specifies how to conduct acute toxicity testing for end-use products (EP). EP 

1783 testing is conducted on the product as formulated for sale and distribution. From the EP 

1784 acute toxicity studies, EPA derives toxicity categories which are then used to determine 

1785 the precautionary labeling statements on the product. However, it is common for some 

1786 products to be diluted before being used. The use-dilution testing is in addition to the 

1787 as-formulated-for-sale testing since there are exposures to both. Acute toxicity testing 

1788 on the product that has been diluted-for-use supplies the information needed to derive 

1789 precautionary statements for the user of the product. EPA is revising proposed test 

1790 note 2 to make this clearer. 

1791 D. The Phrasing “limited portion of the human lifespan” 

1792 1. Comment. Several commenters asked EPA to identify the criteria to 

1793 determine “repeated human exposure over a limited portion of the human life span.” 

1794 They asked EPA to specifically describe what the phrase “human exposure is not 

1795 purposeful” means? 

1796 2. EPA’s response. Proposed test note 11 to the proposed toxicology table in § 

1797 158.2230, specifies the triggers that would require the performance of a 90-day oral 

1798 study in the non-rodent. EPA has re-evaluated this test note and decided to remove 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 73 of 233 

1799 test note 11 from proposed part 158, subpart W. Proposed test note 11(, subparagraph 

1800 i). contained the phrase “repeated human exposure over a limited portion of the human 

1801 life span.” EPA agrees that this phrase is not useful. Proposed test note 11(, 

1802 subparagraph ii). contained a trigger for any indirect food use that would have been 

1803 considered to be a “low exposure.” Given the restructuring of the final Toxicity Data 

1804 Requirements Table, i.e., the shift away from using high and low exposure as the table 

1805 headers to a food/nonfood approach, test notes 11(.i). and 11(.ii). are no longer needed. 

1806 In the final Toxicity Table in § 158.2230(g), the data required for an indirect food-use is 

1807 specified directly (in the table header) and a trigger is not needed. As discussed in Unit 

1808 X.B, proposed., test note 11 as proposed is replaced by a different test note as part of 

1809 re-numbering in this final rule. 

1810 Proposed Test note 12 to the proposed toxicology table in § 158.2230, 

1811 specifies three triggers that would require the performance of a 21/28-day dermal study. 

1812 EPA has also re-evaluated test note 12 and agrees that the phrases “repeated human 

1813 exposure over a limited portion of the human life span” and “human exposure is not 

1814 purposeful” are not useful. Accordingly, EPA has decided to remove the first two of the 

1815 triggers. Therefore,revised the 21/28 day dermal study trigger. The 21/28 day dermal 

1816 study is now triggered if all of the following criteria are met: 1) the intended use of the 

1817 antimicrobial pesticide product is expected to result in repeated dermal human exposure 

1818 to the product,; 2) data from a subchronic 90-day dermal toxicity study are not 

1819 available,; 3) and the 90-day dermal toxicity study has not been triggered (the third 

1820 proposed trigger). 

1821 E. Mouse Carcinogenicity Study

1822 1. Comment. According to several commenters, the mouse carcinogenicity 

1823 study does not provide useful information, and is, in fact, not suited for 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 74 of 233 

1824 determining/extrapolating human carcinogenicity. They contended that EPA should no 

1825 longer require the mouse carcinogenicity study. This would also mean that there is no 

1826 need for the mouse range-finding study. 

1827 2. EPA’s response. The issue regarding the usefulness of the mouse for 

1828 carcinogenicity testing is one that is currently under debate by the OPP. Currently, 

1829 carcinogenicity testing, whether for conventional pesticides under § 158.500 or for 

1830 antimicrobials under part 158, subpart W requires testing in two rodent species. 

1831 However, OPP is currently conducting a comprehensive analysis of its rodent chronic 

1832 bioassay database to document the utility of the mouse bioassay for both cancer risk 

1833 assessment and Reference Dose (RfD) derivation for non-cancer endpoints. When this 

1834 analysis is completed, a recommendation will be made regarding the testing needed for 

1835 cancer hazard identification. OPP anticipates completing this analysis during 2012. 

1836 Once OPP’s internal review process is complete, then it is likely that EPA would solicit 

1837 review and comment by the FIFRA SAP. If at a later date, the determination is made to 

1838 alter the carcinogenicity data requirements, then appropriate changes would be 

1839 proposed to be made to data requirements and regulations pertaining to conventionals, 

1840 biochemicals and microbials, and antimicrobials through rulemaking. 

1841 F. Ames Assay

1842 1. Comment. A commenter argued that the Ames assay should not be required, 

1843 because it is inappropriate for antimicrobials that kill bacteria. 

1844 2. EPA’s response. It is recognized that the Ames assay may not be useful for 

1845 assessment of mutagenic potential of antimicrobial pesticides, as this test uses strains 

1846 of bacteria as the primary test material, and antimicrobials are designed to kill, among 

1847 other things, bacteria. So, the bacteria may be killed before mutagenic effects are 

1848 demonstrated. However, for some antimicrobial pesticides, the Ames assay has 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 75 of 233 

1849 already been conducted and if the Ames assay was conducted at levels that do not 

1850 cause toxicity to the bacterial strains tested, then the study may be acceptable to fulfill 

1851 the reverse mutation assay requirement. However, if an Ames assay has not yet been 

1852 conducted for a particular antimicrobial, then, the Ames assay should not be conducted. 

1853 In this final rule, test note 32 for the reverse mutation assay requirement toin the final 

1854 Toxicology Table in § 158.2230(g), is revised to allow reliance on previously-conducted 

1855 Ames tests when the bacteria strain was not killed, but to state a preference for assays 

1856 such as an in vitro mammalian cell assay, (e.g., the mouse lymphoma TK +/- assay). 

1857 G. Dermal Absorption Studies

1858 1. Comment. A commenter argued that EPA should accept in vitro skin 

1859 penetration data. According to the commenter, accepting such data would harmonize 

1860 with requirements in the European Union (EU) and elsewhere. The commenter pointed 

1861 to well-established OECD guidelines for these studies. The commenter also asserted 

1862 that proposed test note 37 to the proposed toxicology table in § 158.2230, addressing 

1863 the requirement for a dermal absorption study, should not apply to corrosive/irritant 

1864 products. 

1865 2. EPA’s response. The Agency has, on a case-by-case basis, used in vitro

1866 dermal absorption studies to determine the magnitude of dermal absorption of pesticide 

1867 chemicals. However, the Agency has not adopted an official policy of using only in vitro

1868 data to support these decisions. The OECD guideline 428, while describing an in vitro

1869 method for dermal absorption, does not rule out the use of in vivo data along with in 

1870 vitro data to determine dermal absorption. Further, the test guideline notes that formal 

1871 validation studies of the in vitro method have not been performed. 

1872 The Agency is working on developing a more formal policy that would use both in 

1873 vivo and in vitro dermal penetration data in a weight-of-evidence (WOE) determination 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 76 of 233 

1874 in appropriate cases. The Agency would always consider QSAR or other models, 

1875 submitted in support of the determination of dermal absorption. The decision to accept 

1876 such information is the Agency’s, based on its review and evaluation of the submission. 

1877 Proposed Test note 37 to the proposed toxicology table in § 158.2230, specifies 

1878 that the trigger for requiring a dermal penetration study are the results from a risk 

1879 assessment “assuming that dermal absorption is equal to oral absorption.” This means 

1880 that EPA assumes 100 percent dermal absorption. If a subchronic dermal study and/or 

1881 dermal absorption data are not available, then a risk assessment could be conducted 

1882 using the default assumption of equivalent absorption by the dermal and oral routes of 

1883 exposure. If unacceptable risks are found, then either the subchronic dermal study or a 

1884 dermal absorption study would be required. EPA recognizes that the assumption of 100 

1885 percent dermal absorption is conservative; however, this assumption would only be 

1886 used in the absence of an acceptable dermal subchronic study or dermal absorption 

1887 data. In this final rule, test note 37 to the Toxicology Table in § 158.2230(g), is revised 

1888 to clarify this process. EPA also agrees that corrosive/irritant products should not be 

1889 tested in dermal absorption studies. Therefore, test note 3 to the Toxicology Table in § 

1890 158.2230(g), which specifies that testing is not needed for corrosive materials, is added 

1891 as a trigger for not requiring the dermal absorption study. 

1892 H. Tiering

1893 1. Comment. One commenter argued that EPA has not provided meaningful 

1894 tiering for its toxicology requirements for antimicrobials. Another commenter claimed 

1895 that exposure alone is not an appropriate criterion to use for a tiered testing scheme, 

1896 that both exposure and risk should be considered. A third commenter asserted that the 

1897 high and low human exposure categories for toxicity are not appropriate and suggested 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 77 of 233 

1898 that a tiered scheme such as that used for environmental fate data requirements would 

1899 be more appropriate. 

1900 2. EPA’s response. EPA disagrees with these comments. In its proposed rule 

1901 EPA proposed a tiered testing scheme for toxicology testing that was based on the 

1902 amount of exposure as defined by use patterns. Based on its experience in conducting 

1903 risk assessments, EPA understands which use patterns have exposures of higher 

1904 duration and magnitude, and therefore could have greater risks. Use patterns with 

1905 higher exposures require more submission of more data than use patterns with lower 

1906 exposures. 

1907 I. Guideline Numbers in CFRthe Code of Federal Regulations

1908 1. Comment. A commenter stated that the final rule should not specify a 

1909 guideline number. Instead, the data requirement tables should describe the endpoint in 

1910 question, and the information needed for EPA’s risk assessment. OPP could develop 

1911 guidance that could be placed on the web. 

1912 2. EPA’s response. EPA agrees with this comment. The guideline number 

1913 column could be removed from the table. Instead, EPA could have an internet page 

1914 that describes multiple methods of fulfilling the data requirements. An internet table 

1915 could be updated faster to reflect newer techniques than rulemaking to revise a 

1916 regulation in the CFR. However, there is also value in having the guideline number in 

1917 the CFR, which then shows the available guidelines relevant to the particular study that 

1918 should be considered in addressing the requirement. EPA has made no decision on 

1919 whether or not to initiate a rulemaking to remove all the guideline numbers from the data 

1920 requirement tables in 40 CFR part 158. The tables finalized in subpart W in this rule 

1921 include guideline numbers. 

1922 J. Animal Testing 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 78 of 233 

1923 1. Comment. A commenter requested that EPA specifically state in its 

1924 regulations that non-animal methods are acceptable for fulfilling a data requirement. 

1925 The commenter argued that the Draize study (the acute eye irritation study) in rabbits 

1926 should be eliminated. 

1927 2. EPA’s response. Non–animal test methods are continually being examined for 

1928 use in fulfilling the toxicology data requirements that are used to assess the hazard of 

1929 pesticide chemicals. However, in order for non-animal approaches to be used for 

1930 fulfilling toxicology data requirements, these approaches must first be scientifically 

1931 validated to ensure that they are as good as the existing test method for predicting 

1932 hazard and also assessed to determine whether they meet the Agency’s “3 R” goals of 

1933 reduce, refine, and replace the use of animals in testing. With respect to antimicrobial 

1934 pesticides, the Agency has started to explore such approaches. One example of this is 

1935 the voluntary pilot program for eye irritation testing of antimicrobial pesticides using 

1936 non–animal test methods, found at http://www.epa.gov/oppad001/eye-irritation.pdf.

1937 K. Derivation of 200 Parts per Billion Criterion 

1938 1. Comment. A commenter asked whether the 200 parts per billion (ppb) level 

1939 used as the dividing line between high and low human exposures is the concentration of 

1940 a substance in an adult’s daily food consumption? 

1941 2. EPA’s response. The derivation of the 200 ppb level was previously 

1942 established by FDA for indirect food use biocides, and is described in the proposed rule 

1943 (73 FR 59394, October 8, 2008). (Also, see document 10 (identified in the docket at 

1944 http://www.regulation.gov.) As discussed in the proposed rule, by document ID number 

1945 EPA-HQ-OPP-2008-0110-0010). FDA derived the 200 ppb is derivedlevel by dividing 

1946 FDA’sthe cumulative exposure upper limit of 1000 ppb levelfor food contact substances

1947 by 5 to account for the fact that antimicrobial pesticides (e.g., biocides) are a class of 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 79 of 233 

1948 pesticide that are generally toxic by design. The 200 ppb level is the concentration of 

1949 the antimicrobial residues in or on the food item. EPA is using 200 ppb as a delineation 

1950 consistent with the FDA’s toxicology recommendations for food contact substances. 

1951 Therefore, those indirect food uses that have residues that are less than or equal to 200 

1952 ppb in or on the food item usually have fewer data requirements than those that have 

1953 residues that are greater than 200 ppb in or on the food item. For clarity, the following 

1954 information concerning the 200 ppb level and its derivation from FDA levels has been 

1955 added to § 158.2230(d): 

1956 The 200 ppb level was originally used by the Food and Drug 

1957 Administration with respect to the concentration of residues in or 

1958 on food for tiering of data requirements for indirect food use 

1959 biocides. The Agency has also adopted this same residue level for 

1960 determining toxicology data requirements for indirect food uses of 

1961 antimicrobial pesticides. The 200 ppb level is the concentration of 

1962 antimicrobial residues in or on the food item. 

1963 

1964 L. Use of OECD Guidelines for EPA Registrations 

1965 1. Comment. A commenter asked EPA to consider incorporating the following 

1966 OECD guidelines into the new part 158, subpart W to reduce the number of animals 

1967 killed in LD50 tests: OECD guidelines 436; Acute Inhalation Toxicity - Acute Toxic Class 

1968 Method, and revised 223; Avian Acute Oral Toxicity Test, and Short Guidance on the 

1969 Threshold Approach for Acute Fish Toxicity. 

1970 2. EPA’s response. OPP does not have a policy for use of OECD 436 for acute 

1971 inhalation toxicity. If a study conducted according to OECD 436 were submitted for the 

1972 purpose of assessing acute inhalation toxicity, EPA would review and accept the results 

1973 if the study were conducted in an acceptable manner and provided sufficient information 

1974 to fulfill the data requirement. Similarly, if a study conducted according to OECD 223 or 

1975 the Threshold Approach, were submitted, then EPA would review the study and then 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 80 of 233 

1976 make a determination on whether the study was conducted in an acceptable manner 

1977 and provided sufficient information to fulfill the data requirement. 

1978 M. Alternative Formats for Toxicology Data Requirements Table Suggested by 

1979 Commenters

1980 1. Comment. In the comments submitted to EPA, the commenters suggested 

1981 two alternative toxicity data requirement approaches for EPA to consider. Alternative 

1982 approach 1 was organized in paragraphs and alternative approach 2 was in a table 

1983 format similar to that proposed by EPA. 

1984 2. EPA’s response. The commenters provided two alternative approaches for 

1985 toxicology data requirements for antimicrobials. As stated by the commenter, 

1986 alternative approach 1 was “intended to provide clearer instructions to registrants,” 

1987 attempted “to fully incorporate the new science” of integrative approaches to testing, 

1988 and included “a threshold concept for toxicological concerns.” (ACC Comment,

1989 identified in the docket at http://www.regulations.gov;by document ID number EPA-HQ1990 OPP-2008-0110-0088.6; Appendix E, entitled “Comments on Proposed Data 

1991 Requirements for Toxicology” p. 24). The commenter did not provide to EPA the same 

1992 or similar table-type of format used for part 158 data requirements. There were no test 

1993 notes to define the triggers for moving from tier to tier. The commenter acknowledged 

1994 that their suggested alternative approach 1 would require “expert scientific judgment” (p. 

1995 25), and also discussed that EPA in the proposed rule (73 FR 59423) that EPA had 

1996 indicated the need forto develop scientific position papers, and recommendations for 

1997 internal and external review of integrative approaches. EPA considers alternative 

1998 approach 1 to be a dramatic departure from EPA’s proposal, and agrees with the 

1999 commenter that certain scientific issues may not be ready for codification. EPA does 

2000 not believe, at this time, that this approach meets the needs of the Agency, or has any 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 81 of 233 

2001 advantages over the table format. EPA found the paragraph explanations unclear. As 

2002 acknowledged by the commenter, the paragraph format would result in a more complex 

2003 decision tree that would require a significantly greater amount of interpretation and 

2004 consultation when compared to the existing table formats. There would be a significant 

2005 learning curve for both EPA and those members of the public that have become 

2006 accustomed to data requirement tables such as in part 158. Within this response, EPA 

2007 has responded to alternative approach 1 in totality. EPA notes that the individual 

2008 scientific issues raised within the paragraphs are addressed separately, as they were 

2009 separated into the various disciplinary areas of the toxicology comments. 

2010 EPA has also evaluated alternative approach 2. This alternative approach is in a 

2011 table-type of format with a strict split between food and nonfood uses. The test notes 

2012 developed by the commenters are extremely detailed and contain information that EPA 

2013 believes is more appropriate in guidance. However EPA has used the suggested test 

2014 notes to revise its proposed testnotesthe test notes in this final rule as appropriate. For 

2015 example, the commenters’ suggested test note 32 to the in vivo cytogenetics study is 

2016 clearer than EPA’s proposed test note 34. Therefore EPA is revising test note 34 to the 

2017 final Toxicology Table in § 158.2230(g), accordingly.

2018 As discussed previously, as a result of comments received, EPA is no longer 

2019 using the terms “high human exposure” and “low human exposure” as proposed for the 

2020 antimicrobial toxicology data requirements table. Instead, in the final rule, EPA is now 

2021 using a food/nonfood approach with some similarities to that of the toxicology data 

2022 requirements table for conventional pesticides to distinguish the use patterns with 

2023 higher exposure that need more toxicity data from those that need less. Accordingly, 

2024 the table headers for the Toxicology Data Requirements Table in the final rule are: 

2025 “Direct Food Uses;” “Indirect Food Uses (>200 ppb);” “Indirect Food Uses (≤200 ppb);” 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 82 of 233 

2026 “SwimmersSwimming Pools, Aquatic Areas, Wood Preservatives, Metal Working 

2027 Fluids;” and “All Other Nonfood Uses.” 

2028 Unlike conventional pesticide chemicals, a strict food/nonfood use “split” for 

2029 delineating data requirements is not appropriate for antimicrobial chemicals. Such an 

2030 approach does not fully address the unique use patterns for antimicrobials, most 

2031 specifically, those involving indirect food uses. As a result of comments received, EPA 

2032 decided to employ a modification of the food/nonfood approach to delineate the specific 

2033 data requirement needs for antimicrobial pesticides. 

2034 The commenter has also asked that EPA include within subpart W a new § 

2035 158.2235 which would be analogous to 40 CFR 158.510 for conventional chemicals 

2036 (Tiered Testing Options for Nonfood Use Pesticides). EPA does not believe this is 

2037 needed for antimicrobials. Once it has been determined that the use is nonfood, then 

2038 certain of the nonfood use scenarios require the submission of more data, and certain 

2039 require the submission of less data. As specified in the column headings for Nonfood 

2040 Uses, swimming pools, aquatic areas, wood preservatives, and metal working fluids 

2041 require a particular set of data. All other nonfood uses require less data. Thus, the 

2042 tiering is already built into the approach used for antimicrobials. 

2043 XI. Discussion of Key Comments on Nontarget Organism Data Requirements 

2044 The following represent the significant comments received on the need for and 

2045 evaluation of nontarget organism studies as proposed by EPA. Changes from the 

2046 proposed rule to the final rule are also described. 

2047 A. Need for Ecotoxicity Data for Indoor Uses 

2048 1. Comment. Several commenters argued that there are few antimicrobial use 

2049 patterns where ecological effects information would be relevant to an assessment under 

2050 FIFRA because there is no expectation of environmental exposure.
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 83 of 233 

2051 2. EPA’s response. As explained in the proposed rule, there is now a greater 

2052 concern regarding indoor uses of antimicrobials because those uses can lead to 

2053 environmental exposure when they go down -the -drain. The Agency and the scientific 

2054 community have more recently become concerned with pharmaceuticals and personal 

2055 care products (PPCPs), which are now recognized as environmental contaminants. A 

2056 subset of these PPCPs includes antimicrobial pesticide products, some of which are 

2057 being detected in various environmental compartments/media [e.g., surface water and 

2058 WWTP biosolids]. As discussed in the proposed rule (73 FR 59407), these findings are 

2059 notable, because many of the antimicrobial pesticides detected are registered for only 

2060 indoor use patterns. 

2061 There are many uses for which a high potential for environmental exposure 

2062 exists, especially outdoor uses such as wood preservatives, ballast water treatments, 

2063 antifoulant paints and coatings, aquatic areas, and others. These uses may require a 

2064 more extensive data set that could include acute and chronic tests in both freshwater 

2065 and saltwater, and possibly in the sediment as well as the water column. If the effluent 

2066 from a WWTP is likely to contain an antimicrobial pesticide, or if the antimicrobial is 

2067 likely to partition to the sludge that is derived during the treatment process, then indoor 

2068 uses could require additional testing to further characterize the hazard and the risk. 

2069 A. Transformation Products

2070 1. Comment. Several commenters questioned, how a registrant would 

2071 determine if “transformation products” would need to be tested?. With regard to the 

2072 criteria for when testing is required on transformation products, another commenter 

2073 stated their belief that any data developed to assess the potential risk to nontarget 

2074 organisms should be developed with the appropriate residue of concern (ROC) (i.e. 

2075 degradation product, metabolite, or TGAI) rather than always testing with the TGAI. Still 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 84 of 233 

2076 another commenter asked how would EPA determine that the transformation products 

2077 are “more toxic, persistent, bioaccumulative or have been shown to cause adverse 

2078 effects in mammalian or aquatic reproductive studies?”.” Finally, a commenter 

2079 requested that EPA should explain what is considered “stable” in the environment in 

2080 proposed test note 3 to the proposed nontarget organism table in § 158.2240. 

2081 2. EPA’s response. The Agency evaluates the need for nontarget organism 

2082 testing of transformation products on a case-by-case basis, using several sources of 

2083 information, which includes, most importantly, environmental fate data. EPA proposed 

2084 to require nontarget organism testing of transformation/degradation products or 

2085 leachate residues in proposed § 158.2240(a)(3) and (4). To respond to this comment, 

2086 EPA also considered a similar comment on transformation/degradation products or 

2087 leachate residues for environmental fate testing (see Unit XIV.B)..). In response to 

2088 these comments, EPA determined to clarify and revise the criteria for testing of 

2089 transformation/degradation products and leachate residues for nontarget plant and 

2090 organisms, and environmental fate, (§ 158.2250(b), (§§158.2240(a)(3),) and 

2091 158.2280(a)(2)) to read as follows: 

2092 Data on transformation/degradation products or leachate residues 

2093 of the parent compound are also required to support registration, if 

2094 the Agency determines that the 

2095 transformation/degradation/leachate products meet one of the 

2096 following criteria: 

2097 (i) More toxic, persistent, or bioaccumulative than the parent, 

2098 (ii) Have been shown to cause adverse effects in mammalian or 

2099 aquatic reproductive studies, or 

2100 (iii) The moiety of concern (i.e., functional group in the parent 

2101 chemical molecule that imparts adverse effects) remains intact. 

2102 For nontarget plant protection (158.2250(b)) EPA determined to revise the 

2103 criteria to read as follows:

2104 (b) Data on transformation/degradation products or leachate residues 

2105 of the parent compound are also required to support registration, if
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 85 of 233 

2106 the transformation/degradation/leachate products meet

2107 one of the following criteria:

2108 (1) More toxic, persistent, or bioaccumulative than the parent,

2109 (2) Have been shown to cause adverse effects in mammalian or aquatic

2110 reproductive studies, or

2111 (3) The moiety of concern (i.e., functional group in the parent chemical

2112 molecule that imparts adverse effects) remains intact.

2113 As explained in Unit XIV.B., environmental fate studies provide information on 

2114 the stability and persistence of the active ingredient and degradation products in the 

2115 various environmental media. If the environmental fate studies on the parent indicate 

2116 the transformation/degradation product(s) is, for example, more persistent in soils, then 

2117 it is possible that nontarget plants or animals could be exposed to the degradate. Once 

2118 the transformation products and the environmental compartment in which they occur are 

2119 identified, then the available toxicology data (e.g., reproduction tests, developmental 

2120 tests, non-rodent chronic studies) are reviewed to determine toxicity. 

2121 After reviewing all available information, then EPA would use these criteria to 

2122 determine if ecological effects data on the transformation/degradation products or 

2123 leachate residues are required for either nontarget organisms or nontarget plants. EPA 

2124 believes that nontarget plant protection data may sometimes be needed when the 

2125 Agency begins conducting species-specific endangered species assessments for 

2126 antimicrobial pesticides. 

2127 EPA does not use the term “residue of concern (ROC)” in the final Nontarget 

2128 Organisms Data Requirements Table. Instead, the appropriate test material(s), such as 

2129 TGAI, degradate, or TEP, is specified in the data requirements table in § 158.2240. 

2130 This approach is also used for the conventional nontarget organism table in part 158. 

2131 Generally, for ecological testing, the TGAI testing is performed first, and then additional 

2132 testing on a transformation product may be required based on the process described 

2133 abovepreviously. Depending on how fast a substance decays, a nontarget organism or 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 86 of 233 

2134 plant could actually be exposed to a mixture of the parent and one or more 

2135 degradation/transformation products. 

2136 C. Test Note 7 to the Nontarget Organism Table and Wood Preservatives

2137 1. Comment. Proposed Test note 7 to the proposed nontarget organism data 

2138 requirements table in § 158.2240 specifies the triggers for requiring typical end-use 

2139 product (TEP) testing for the acute freshwater invertebrate study and acute freshwater 

2140 fish study. A commenter asked whether, even though, the wood preservatives use 

2141 pattern is specified as “NR,” could the TEP testing be required because of the triggers in 

2142 test note 7. 

2143 2. EPA’s response. Proposed test note 7 also triggered the testing for the TEP 

2144 acute estuarine and marine organisms toxicity testing. EPA agrees that the combination 

2145 of “R”s, “CR”s, “NR”s and the current structure of proposed test note 7, is confusing and 

2146 that clarification is needed. 

2147 The data requirements for TEP testing and proposed test note 7 was also 

2148 considered in light of the Agency’s recent determination based on comments received 

2149 (see Unit VI.B).) on EPA’s current practice of conducting risk assessments for wood 

2150 preservatives based on land-only versus a land and aquatic predetermined use pattern. 

2151 All wood preservative risk assessments will now be performed considering that the 

2152 treated wood could end-up either on both the land or in the aquatic environment. As 

2153 previously discussed, there are multiple pathways for wood preservative degradates 

2154 and/or leachates to reach surface water. EPA has also determined to conduct a down -

2155 the -drain assessment for all appropriate use patterns which would include wood 

2156 preservatives, and antifoulant paints and coatings (see Unit XV.A)..). For wood 

2157 preservatives, these determinations mean that additional ecological testing is required 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 87 of 233 

2158 to conduct an ecological risk assessment, and the following changes are made to the 

2159 wood preservative testing column: 

2160  Acute freshwater invertebrates toxicity (TEP testing): change from “NR” to 

2161 “CR”; 

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

2163  Acute estuarine and marine organisms toxicity (TEP testing): change from 

2164 “NR” to “CR”. 

2165 For antifoulant paints and coatings, the determination to conduct a down-the2166 drain assessment also means that additional data could be needed for the Down -the -

2167 drain assessment, and the following changes have been made to the antifoulant paints 

2168 and coatings testing column: 

2169  Acute freshwater invertebrates toxicity (TEP testing): change from “NR” to 

2170 “CR”; 

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

2172  Acute estuarine and marine organisms toxicity (TEP testing): change from 

2173 “NR” to “CR”. 

2174 EPA believes that simplifying the data requirements that reference test note 7 to 

2175 the final Nontarget Organism Table in § 158.2240(c) so that these requirements are CR 

2176 for all use patterns is clearer, and also closer to the suggestions made by the 

2177 commenters in their suggested nontarget organism data requirements table. Their 

2178 suggested table was predominantly “CR” for aquatic uses. Therefore, in this final rule, 

2179 test note 7 triggers the “CR” studies. 

2180 However, changing all the use patterns to “CR” for the TEP studies means 

2181 changing the “R” proposed for the aquatic use, and industrial processes and water 

2182 systems use patterns for the acute freshwater invertebrates toxicity study and the acute 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 88 of 233 

2183 freshwater fish toxicity study, to “CR.” To account for this change proposed test note 7 

2184 to the proposed nontarget organism table in § 158.2240 has been revised in the final 

2185 rule to include an additional trigger (see § 158.2240(d) test note 7(.iv)): ). Data are 

2186 required when “the end-use antimicrobial product will be applied directly into an aquatic 

2187 environment.” EPA believes that the implications of this trigger are equivalent to the 

2188 “R” and essentially this is a non-change. These changes are summarized belowhere for 

2189 both the aquatic areas and industrial processes and water systems testing column: 

2190  Acute freshwater invertebrates toxicity (TEP testing): change from “R” to 

2191 “CR”; 

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

2193  Acute estuarine and marine organisms toxicity (TEP testing): no change. 

2194 Nontarget organism toxicity testing of the TEP should be infrequently required for 

2195 the antifoulant paints and coatings use pattern because for this use pattern, the TEP 

2196 could be the paint. Because the testing for aquatic organisms is done in water, the test 

2197 material must be soluble in water, or made soluble by addition of an appropriate solvent, 

2198 if one exists, or other appropriate mechanical methods. Paint is not soluble and there 

2199 may not be a way to make it soluble. Since these studies are often run in glass aquaria, 

2200 the paint could coat the sides of the glass and the test animals themselves. The paint 

2201 could ruin test equipment by clogging lines and injection nozzles. Therefore EPA has 

2202 added a new test note 5, which is replacing proposed test note 5 to the proposed 

2203 nontarget organism in § 158.2240. New test note 5 to the final Nontarget Organism 

2204 Table in § 158.2240(c) states that an applicant should request a waiver if the TEP 

2205 cannot be tested. 

2206 EPA also notes that a test note specifying the number of species to be tested 

2207 was omitted in the proposed rule for the TEP testing for acute freshwater fish toxicity. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 89 of 233 

2208 This test note is needed for clarity. Test note 3 to the final Nontarget Organism Table in 

2209 § 158.2240(c) has been added to the line for acute freshwater fish toxicity. Test note 3

2210 to the final Nontarget Organism Table in § 158.2240(c) has been added to the line for 

2211 acute freshwater fish toxicity. Instead of “greater than 1 ppm or 1 mg/L” as indicated in 

2212 the proposed rule, the toxicity trigger has been corrected to read “less than or equal to 1 

2213 ppm or 1 mg/L.” If the LC50 is greater than 1 ppm this means that chemical tested was 

2214 moderately to practically non-toxic on an acute basis. If the LC50 is less than 1 ppm this 

2215 means that chemical tested was highly to very highly toxic on an acute basis and would 

2216 have a serious adverse affect(s) on the organism tested at low concentrations. For 

2217 clarity, in test note 3 to the Nontarget Organism Table, EPA has corrected the draft final 

2218 rule to ensure that we codify the appropriate trigger (less than or equal to) to indicate 

2219 that testing is needed for chemicals that demonstrate high to very high toxicity on an 

2220 acute basis. 

2221 D. Acute and Chronic Toxicity Data 

2222 1. Comment. A commenter argued that it is essential to have both acute and 

2223 chronic toxicity test results for at least one freshwater invertebrate, vertebrate, and plant 

2224 species, and at least one marine/estuarine invertebrate, vertebrate, and plant species. 

2225 2. EPA’s response. EPA proposed to require acute tests for both a coldwater 

2226 and warmwater freshwater fish, an invertebrate, and one or more aquatic plants. For 

2227 marine/estuarine species, for most use patterns, EPA proposed to conditionally require 

2228 acute testing with a fish and two aquatic invertebrate species, including a bivalve, when 

2229 the Agency believes there is a potential for the active ingredient or a potentially toxic 

2230 degradate to reach the estuarine/marine environment through transport (e.g., leaching, 

2231 runoff) from the treatment site. In such a situation, chronic testing with one or more 

2232 marine/estuarine species also may be required if the Agency believes that chronic 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 90 of 233 

2233 exposure is likely. These studies also are required for those uses where the pesticide 

2234 product is applied directly into the marine/estuarine environment. 

2235 As to chronic testing, EPA proposed to require the fish early life stage and the 

2236 aquatic invertebrate life-cycle studies for the industrial processes and water systems 

2237 (once-through), antifoulant coatings and paints, and aquatic areas use patterns. At that 

2238 time, EPA also proposed to conditionally require the same two studies for the low 

2239 environmental grouping (now called the all other use patterns category) and wood 

2240 preservatives. 

2241 However, based on this and other comments, EPA has re-evaluated the 

2242 nontarget organism data needed for a registration decision and concluded that 

2243 additional acute and chronic data are needed. See Units V.B,., X.C,., and XIV.F. for 

2244 discussions on the rationale for and descriptions of the changes. 

2245 EPA does not require chronic testing for plants. Plant species encompass 

2246 many different life spans. Phytoplankton reproduce quickly and have extremely short 

2247 life spans. Annuals live for 1 year. Many perennials do not actually live for multiple 

2248 years, but reproduce from seeds year after year. The plant species that live the longest 

2249 would be woody species, such as trees. EPA does not believe that antimicrobial use 

2250 patterns impact terrestrial areas such that chronic exposures occur: To EPA’s 

2251 knowledge, no adverse chronic effects to terrestrial plants caused by pesticides have 

2252 been documented on plants. Any effect on terrestrial plant species has been 

2253 categorized as an acute effect and would be covered by current testing procedures. 

2254 Chronic effects of aquatic plants are covered by the acuteaquatic testing guidelines. 

2255 Algae isare used as the primary test species for evaluating effects to the acute testing of

2256 aquatic plants. The testing is based on growth parameters and the tests normally run 

2257 for periods of time that would include several generations of the algae. The results from 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 91 of 233 

2258 the acutethese algal studies, while only conducted over a few days, would be similar to 

2259 those obtained from chronic testing in other species, and cwould be used to assess any 

2260 chronic effects to aquatic plant species. 

2261 D. Avian Studies

2262 1. Comment. In proposed test note 4 to the proposed nontarget organism table 

2263 in § 158.2240, which triggers the avian dietary study, EPA specified a trigger of 100 mg 

2264 ai/kg (milligrams active ingredient/kilogram) for additional testing. A commenter 

2265 requested information on why this trigger was selected. The commenter also claimed 

2266 that EPA could use exposure tools to conduct an initial assessment based on Tier 1 

2267 data, and then trigger additional testing based on risk. 

2268 2. EPA’s response. OPP has long used this value as an indication of toxicity to 

2269 birds. As specified in 40 CFR 156.85(b)(3), any pesticide (including conventional 

2270 pesticides) that is intended for outdoor use with an avian acute oral LD50 of 100 mg 

2271 ai/kg or less requires a precautionary label statement that the pesticide is toxic to birds. 

2272 EPA believes that if 100 mg ai/kg is appropriate to trigger a precautionary label 

2273 statement, then it is also appropriate to use as a trigger for testing. Therefore, if the 

2274 avian oral acute toxicity study indicates an oral LD50 of 100 mg ai/kg or less, then an 

2275 avian dietary study is required. 

2276 In the proposed rule, for the avian dietary toxicity study, EPA proposed to require 

2277 testing on two species for the aquatic areas and to conditionally require testing on one 

2278 avian species for all of the other use patterns. The comments reviewed and evaluated 

2279 by EPA on avian toxicity testing included the commenter’s suggested data requirements 

2280 table for nontarget organisms, which specified “CR” for all avian testing. EPA agrees 

2281 with the commenter that “CR” is appropriate for the avian dietary toxicity and avian 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 92 of 233 

2282 reproduction studies for all use patterns. This simplifies the test notes and with the 

2283 appropriate triggers EPA would be able to require the needed testing. 

2284 The following changes have been made to the aquatic areas column: 

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

2286  Avian reproduction: change from “R” to “CR”. 

2287 Test note 4 to the final Nontarget Organism Table in § 158.2240(c) triggers the 

2288 avian dietary toxicity study based on the results of the avian acute toxicity study. For 

2289 the avian dietary study, testing in a second species would be triggered based on the 

2290 results of the avian dietary testing in the first species. Since the second test species will 

2291 be required based on the results of the first species proposed test note 5 is no longer 

2292 needed and is being removed. Test note 6 to the final Nontarget Organism Table in § 

2293 158.2240(c) would trigger the avian reproductive study based on one or more of four 

2294 specific criteria: There were no revisions to these criteria from the proposed rule to the 

2295 final rule. 

2296 F. Water Quality Criterion 

2297 1. Comment. A commenter argued that the registrants of any antimicrobial 

2298 pesticide that has the potential to be discharged either directly or indirectly to surface 

2299 water should be required to supply any additional data needed to derive a water quality 

2300 criterion for the pesticide in question. 

2301 2. EPA’s response. As discussed in the conventionals’ Response to Comments 

2302 Document in docketEPA-HQ-OPP-2004-0387 (p. 104) at http://www.regulations.gov,),

2303 the Agency’s pesticide registration process, including its data requirement regulations, 

2304 adequately considers the endpoints that are protected under the Clean Water Act 

2305 (CWA) as administered by the Office of Water (OW). When acceptable data are 

2306 available, OPP uses these data in its risk assessment process. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 93 of 233 

2307 The purpose of a water quality criterion under the CWA is to determine the level 

2308 at which a water body may be at risk for environmental damage. The purpose of certain 

2309 data requirements for pesticide registration is to allow the Agency to determine the 

2310 ecological risk of using a pesticide. Thus, these program offices within EPA have 

2311 similar goals. While EPA has developed guidelines for developing Water Quality 

2312 Criteria (WQC), the Agency has also recognized that WQC can be developed with a 

2313 more limited data set. 

2314 Pesticide registration data are valuable in assessing water quality risks. As noted 

2315 in EPA’s 2005 Response to Comments Document on the conventional pesticides, 

2316 EPA’s OW and OPP together developed aquatic life benchmarks for 71 pesticides or 

2317 pesticide degradation products for States to use to establish targets for safe levels of 

2318 pesticides for aquatic plants and animals. The benchmarks are derived from data 

2319 submitted to EPA for pesticide registration. As of April 18, 2011, there are 242 pesticide 

2320 chemicals with aquatic benchmarks on EPA’s website 

2321 (http://www.epa.gov/oppefed1/ecorisk_ders/aquatic_life_benchmark.htm). 

2322 G. Sediment Testing 

2323 1. Comment. The commenter asserted that EPA did not consider the 

2324 environmental fate of a compound (such as the tendency of a chemical to 

2325 absorb/desorb) when considering the need for sediment testing. 

2326 2. EPA’s response. EPA disagrees with this comment. Test notes 17 and 18 to 

2327 the final Nontarget Organism Table in § 158.2240(c) trigger the sediment studies based 

2328 on the results of the aerobic soil or aquatic metabolism studies and knowledge of the 

2329 physical/chemical properties which express the environmental fate of the antimicrobial 

2330 pesticide chemical. The soil partition coefficient (Kd) is used as an expression of the 

2331 binding capability of the chemical to sediments. The Agency’s justification for using Kd
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 94 of 233 

2332 >50 as a criterion for requiring sediment testing is that this value would capture those 

2333 chemicals with about 80 percent adsorption to sediments (relative to organic carbon). 

2334 The octanol-water partition coefficient (Kow) and the soil organic carbon-water 

2335 partition coefficient (Koc) also are used by EPA as part of its decision process. Both 

2336 values are frequently more available than either the Kd or half-life values. Test note 17, 

2337 the trigger for requiring an acute sediment study, considers all four of these values. 

2338 Next, as explained in test note 18, the chronic sediment study is triggered based 

2339 on the results of the acute sediment study as well as a re-examination of the Kow,, Koc, 

2340 and Kd . 

2341 XII. Discussion of Key Comments on Nontarget Plant Protection Data 

2342 Requirements 

2343 The following represent the significant comments on the need for and evaluation 

2344 of nontarget plant protection studies as proposed by EPA. The changes from the 

2345 proposed rule to final rule are also described.

2346 A. Triggers for Higher-Tiered Plant Studies 

2347 1. Comment. One commenter asked EPA to explain the criteria used to trigger 

2348 higher-tiered plant studies based on the results of the algal studies. 

2349 2. EPA’s response. The criteria to trigger higher-tiered plant studies are 

2350 specified in proposed test notes 2 and 5 to the proposed nontarget plant protection table 

2351 in § 158.2250. A toxicity level (EC50 <1 ppm) indicates that the antimicrobial pesticide 

2352 would have serious adverse affect(s) on algae at low concentrations. This could have 

2353 serious consequences to nontarget algae species. Therefore, at this toxicity level, 

2354 additional higher-tiered testing is required to further characterize the potential adverse 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 95 of 233 

2355 affects to aquatic plants. EPA is retaining the toxicity trigger of <1 ppm in test note 5 to 

2356 the final nontarget plant protection table in § 158.2250. 

2357 In evaluating proposed test note 2 to the proposed nontarget plant protection 

2358 table in § 158.2250, EPA has considered the commenter’s suggested table for 

2359 nontarget plants. For the seedling emergence study, the commenter used “CR” for 

2360 most use patterns and suggested that the seedling emergence study should only be 

2361 required “when environmental exposure is likely to result under normal usage conditions 

2362 as determined by appropriate assessment methods.” Another comment (see response 

2363 to comment 140.27 in the Response to Comments Document in the docket at 

2364 http://www.regulations.gov) advocated for the use of a Risk Quotient (RQ) approach for 

2365 assessing plants. 

2366 Based on this evaluation, EPA believes using “CR” for the seedling emergence 

2367 study when triggered by a level of concern approach (RQ approach) would provide EPA 

2368 with the required data when needed. Test note 2 to the final nontarget plant protection 

2369 table in § 158.2250 now reads as: Data are required if the risk quotient from any 

2370 aquatic plant growth Tier II study exceeds a level of concern for aquatic plants. 

2371 However, test note 2 also triggers the aquatic plant growth (aquatic vascular 

2372 plant) study, and is still the appropriate trigger for that study. Today With this final rule, 

2373 EPA is adding a new test note 10 to the final Nontarget Plant Protection Table in § 

2374 158.2250, which will read the same as the original, proposed test note 2 to the 

2375 proposed nontarget plant protection table in proposed § 158.2250. 

2376 B. Alternative Format for Plant Protection Data Requirements Table 

2377 1. Comment. In the comments submitted to EPA, the commenters suggested an 

2378 alternate antimicrobial plant protection data requirements table. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 96 of 233 

2379 2. EPA’s response. The table suggested by the commenter is not adequate to 

2380 evaluate the hazards and risks to nontarget plants from antimicrobial pesticides. The 

2381 suggested table did not include test guideline numbers, changed and reduced the 

2382 number of use patterns, and proposed that all ecotoxicity plant studies are either not 

2383 required or only conditionally required. The commenter contends that there are no 

2384 circumstances where ecological effects plant data are relevant for antimicrobial 

2385 pesticides, and that indoor uses should not be subject to environmental exposure or 

2386 nontarget plant species risk assessments. EPA disagrees with many aspects of these 

2387 comments and the suggested ecotoxicity data requirements table for plant species. 

2388 As previously discussed in the preamble to the proposed rule (73 FR 59406-7) 

2389 and in Units III. and V. of this rule, EPA disagrees that exposure for nontarget plants 

2390 should be presumed to be minimal or nonexistent for antimicrobials applied indoors, or 

2391 that tests are not required if the test organism is the target species for the pesticide (see 

2392 testnotesACC comment, identified in the docket by document ID No. EPA-HQ-OPP2393 2008-0110-0088.7, p. 12, test notes 1 and 2 to the commenter’s suggested table). 

2394 Moreover, there are many outdoor uses of antimicrobials that are not addressed in the 

2395 commenter’s suggested table. FIFRA mandates that EPA conduct a risk assessment 

2396 for any uses for which exposure may occur in the various environmental 

2397 compartments/media. Those risks are assessed separately for the various taxa 

2398 including plants, categories (e.g., freshwater, saltwater), and short-term (i.e., acute) and 

2399 longer-term (i.e., chronic) exposures. Assessing these potential risks necessitates 

2400 having an appropriate ecotoxicity data base for plant exposure and toxicity. This can 

2401 only be accomplished by requiring plant studies for the initial assessment. A tiered 

2402 approach cannot be driven solely by risk quotients derived from a Tier 1 study. The fact 

2403 that an acute risk quotient for a plant species does not exceed a level of concern for 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 97 of 233 

2404 acute risk does not imply that a chronic risk does not exist or that data are not needed 

2405 to assess that risk. The trigger for a chronic test is more likely driven by the frequency, 

2406 duration, or magnitude of the chronic exposure and the environmental properties of the 

2407 pesticide. For example, plants might be subjected to repeated low-level exposure that 

2408 is not acutely lethal but which may impact reproductive success and plant growth. 

2409 EPA disagrees that the test substance for plant studies (in the commenter’s 

2410 table) should be identified simply as the “residue of concern (ROC).” In its proposed 

2411 nontarget plant data requirements table, EPA specified the test material (TGAI, TEP) to 

2412 be used for each study. The test substance determination is made after reviewing the 

2413 required environmental fate and physical/chemical properties data and any other 

2414 available information (e.g., open literature, closely related chemicals) to determine the 

2415 substance of concern for exposure of non-target plants and organisms. For example, if 

2416 an applicant can adequately demonstrate that the TGAI dissipates so rapidly that there 

2417 would be no acute or chronic exposure, TGAI testing may be waived, and instead 

2418 degradate testing may be required. 

2419 The commenter also omitted all guideline numbers from its suggested data table. 

2420 At this time, all data requirement tables in 40 CFR part 158 have guideline numbers 

2421 since this is a method of providing information to applicants. Applicants are not required 

2422 to use these guidance documentsguidelines, but are encouraged to use these test 

2423 guidelines when developing data. Since these guidelines have been developed via a 

2424 rigorous process, as discussed in the preamble to the proposed rule [73 FR 59387], 

2425 “they represent the recommended approach to developing high-quality data that should 

2426 satisfy EPA’s data needs for risk assessment.” 

2427 XIII. Discussion of Key Comments on Applicator and Post-Application Exposure 

2428 Data Requirements 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 98 of 233 

2429 The following represent the significant comments received on the need for and 

2430 evaluation of applicator and post-application exposure studies as proposed by EPA. 

2431 Changes from the proposed rule to the final rule are also described. 

2432 A. Consistency With OSHA and Other Standards 

2433 1. Comment. A commenter asserted that EPA should be consistent with OSHA 

2434 and other standards with regard to exposure limits and handling practices, and 

2435 incorporate the OSHA standards into risk assessment evaluations. The commenter 

2436 also asked that when EPA believes that an OSHA or American Conference of 

2437 Governmental and Industrial Hygienists (ACGIH) standard is not adequately protective 

2438 for an antimicrobial, that the finding should be substantiated. 

2439 2. EPA’s response. The OSHA workplace standard is the permissible exposure 

2440 limit (PEL). When developing a PEL, OSHA considers the toxicity of the chemical, often 

2441 using data from the open literature as well as the feasibility that exposures could be 

2442 reduced to the PEL using process modifications, engineering controls and personal 

2443 protective equipment (PPE). Approximately 500 PELs have been established. 

2444 The ACGIH establishes health–based Threshold Limit Values (TLVs), which are 

2445 non-governmental guidelines used by professional industrial hygienists in making 

2446 decisions about safe levels of exposure to a chemical substance in the workplace. The 

2447 TLVs were established for some chemicals as early as 1946 and they are updated on a 

2448 regular basis as new health effects information becomes available. Like the OSHA 

2449 PELs, the TLVs are based on health effects data from the open literature. However, 

2450 unlike the OSHA PELs, feasibility issues are not considered in establishing TLVs. TLVs 

2451 are not available for most pesticide chemicals. 

2452 However, for those pesticide chemicals with both TLVs and RfCs (Reference 

2453 Concentrations are established by OPP based on studies submitted by the registrants), 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 99 of 233 

2454 the RfCs are often lower than the TLVs. There could be several reasons for such 

2455 differences. The data used by OPP is submitted by the pesticide registrants and the 

2456 toxicity databasedata base is composed of animal studies. So, uncertainty factors are 

2457 used to derive the RfCs (exposure limits). Instead of animal studies, ACGIH prefers to 

2458 rely on epidemiology studies/case reports of human, particularly worker, exposures from 

2459 the literature and on professional judgment. 

2460 For example, ACGIH and OPP established different inhalation limits for 

2461 formaldehyde based on slightly different interpretations of the same literature studies. 

2462 The TLV for formaldehyde is 300 ppb and the OPP “RfC” for occupational uses is 100 

2463 ppb. Although the TLV is greater than the “RfC,” ACGIH does acknowledge in their TLV 

2464 documentation that irritation can occur in some workers at levels of 100 to 300 ppb. 

2465 EPA believes that an existing OSHA or ACGIH standard should be considered as 

2466 part of EPA’s hazard evaluation. However, before using an OSHA or ACGIH standard, 

2467 EPA would review the standard and the health effects (toxicology) documents 

2468 supporting the standard’s development to determine if EPA believes that the standard 

2469 provides adequate protection. EPA agrees with the commenter that EPA’s evaluation of 

2470 an existing OSHA or ACGIH standard should be part of its hazard evaluation 

2471 documentation. 

2472 In its proposed rule, EPA proposed in the applicator exposure table (40 CFR 

2473 158.2260(a)(1)) and the post-application exposure table (40 CFR 158.2270(a)(1)) to 

2474 use established workplace standards, such as OSHA’s. The proposed language was: 

2475 If EPA determines that industrial standards, such as the workplace 

2476 standards set by the Occupational Safety and Health 

2477 Administration, provide adequate protection for a particular 

2478 pesticide or a particular use pattern, applicator exposure data may 

2479 not be required for that pesticide or the use pattern. Applicants 

2480 should consult with the Agency on appropriate testing before the 

2481 initiation of studies. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 100 of 233 

2482 In addressing this comment, EPA realized that this proposed language is 

2483 misplaced and also needs some textual modification. As discussed abovepreviously, 

2484 an OSHA PEL or ACGIH standard is part of hazard evaluation. If the PEL or TLV is 

2485 determined to be adequate to fulfill EPA’s selection of a toxicity endpoint, then the types 

2486 and number of toxicity studies that may be required is impacted, not the need for 

2487 exposure data. Therefore, EPA has removed the language originally proposed for § 

2488 158.2260(a)(1) and § 158.2270(a)(1) concerning use of OSHA standards. With 

2489 modifications, the following language appears in the final toxicity Table,rule in § 

2490 158.2230(e): 

2491 If EPA determines that industrial standards, such as the workplace 

2492 standards set by the Occupational Safety and Health 

2493 Administration, provide adequate protection for a particular 

2494 pesticide or a particular use pattern, additional toxicity data may 

2495 not be required for that pesticide or the use pattern. 

2496 B. Poisoning Incident Data 

2497 1. Comment. “Poisoning incident data” should not be incorporated into this 

2498 regulation unless the EPA can provide criteria to trigger the need for exposure data 

2499 based on poisoning incidents. Regulating based upon anecdotal reports of “poisoning” 

2500 is not appropriate. 

2501 2. EPA’s response. Both proposed § 158.2260(b) and § 158.2270(b) contained 

2502 the following trigger for requiring exposure data: “Scientifically sound epidemiological or 

2503 poisoning incident data indicate that adverse health effects may have resulted from 

2504 handling of the pesticide." EPA understands that anecdotal reports may or may not 

2505 indicate a cause-effect relationship, i.e., that adverse health effects may or may not 

2506 have resulted from exposure to the pesticide. EPA agrees that anecdotal reports may 

2507 not substantiate a clear dose response relationship of “poisoning,” and therefore, when 

2508 not substantiated, are not appropriate for regulatory endpoints. In-depth information on 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 101 of 233 

2509 the dose response is the critical information needed for regulatory endpoints, and 

2510 poisoning incident data rarely include this information. However, EPA’s intention was to 

2511 use scientifically credible information as a trigger for requiring exposure data. Based on 

2512 this comment, EPA has revised the toxicity triggers in § 158.2260 and § 158.2270 to 

2513 clarify that poisoning incident data must have a clear cause effect relationship to 

2514 indicate that adverse health effects may have resulted from exposure to the pesticide. 

2515 C. Use of Existing Post-Application Exposure Data

2516 1. Comment. A commenter argued that there is a significant amount of post2517 application exposure data available that should be considered/used before requiring 

2518 data under FIFRA. 

2519 2. EPA’s response. EPA acknowledges that there are existing exposure data 

2520 either in the literature, or via other governmental organizations such as OSHA, or 

2521 academia, etc. When available and appropriate, EPA uses such exposure data and/or 

2522 information in its risk assessments. For example, the risk assessments for both chlorine 

2523 dioxide and ethylene oxide relied heavily on the workplace air concentration monitoring 

2524 data available in OSHA’s Chemical Exposure Health Database (CEHD), formerly known 

2525 as, Integrated Management Information System (IMIS). To access CEHD, users 

2526 navigate on the OSHA homepage (http://osha.gov/) to Chemical Exposure Health Data 

2527 under the Data and Statistics section towards the bottom right of the page. Users can 

2528 search CEHD by Establishment Name, State, Zip Code, Year Range, Standard 

2529 Industrial Classification (SIC), North American Industrial Classification System Code 

2530 (NAICS), Chemical Abstracts Service Number (CAS), Chemical Name, or Result 

2531 Range. 

2532 Applicants who are aware of existing data that could fulfill a data requirement 

2533 should submit the data to EPA. EPA will consider the appropriateness and robustness 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 102 of 233 

2534 of the data, and, if appropriate, will use the data in the Agency’s risk assessment. 

2535 D. Soil Residue and Indoor Surface Residue Dissipation Studies

2536 1. Comment. A commenter claimed that there is little justification for requiring 

2537 the soil residue dissipation and indoor surface residue dissipation studies. 

2538 2. EPA’s response. In the proposed rule, EPA conditionally required the soil 

2539 residue dissipation study for both occupational and residential scenarios. EPA agrees 

2540 that the likelihood of requiring soil residue dissipation data is low for the majority of 

2541 antimicrobial use patterns. The low likelihood is reflected in the “CR” designation in the 

2542 proposed post-application exposure data requirements table for the soil residue 

2543 dissipation study for both occupational and residential use patterns. No changes are 

2544 needed. 

2545 In the proposed rule, EPA required the indoor surface residue dissipation study 

2546 for both occupational and residential scenarios. However, the likelihood of requiring 

2547 indoor surface residue dissipation data is high for residential products such as 

2548 antimicrobial-treated clothing and plastic consumer items/toys, as well as direct 

2549 applications such as carpet shampoos, laundry detergents, and floor cleaners that are 

2550 antimicrobial products. Therefore, the indoor surface residue dissipation study for the 

2551 residential use sites will remain “R” as proposed. 

2552 However, EPA has re-evaluated the “R” proposed for occupational use sites. 

2553 When compared to residential use sites, occupational use sites are less likely to result 

2554 in the need for indoor surface residue dissipation data. Therefore, the data requirement 

2555 for indoor surface residue data has been revised from “R” to “CR” for occupational uses. 

2556 In most manufacturing settings, there is less contact with surfaces than in most 

2557 residential scenarios. For example, under most circumstances workers do not crawl 

2558 around the floors of manufacturing plants. The need for indoor surface residue 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 103 of 233 

2559 dissipation data for workers is limited by the residue distribution where contact may 

2560 occur. EPA now agrees that the occupational use sites are less likely to result in the 

2561 need for indoor surface residue dissipation data, and therefore, the “R” has been 

2562 revised to “CR.” 

2563 E. Non-Dietary Ingestion Study 

2564 1. Comment. A commenter asserted that the proposed requirement for non2565 dietary ingestion is impractical and unnecessary, and, in fact, could be replaced by 

2566 modeling. 

2567 2. EPA’s response. EPA agrees that the non-dietary ingestion study is 

2568 impractical, as a stand-alone direct measurement study. Non-dietary ingestion 

2569 exposure (i.e., incidental oral ingestion by children) is of potential concern for treated 

2570 articles or surfaces that may be accessed by children. For example, uses such as 

2571 carpet shampoo, hardwood floor treatments, pressure-treated wood, and impregnated 

2572 materials (including but not limited to plastic toys or treated clothing) are assessed for 

2573 non-dietary exposures when toxicity criteria are triggered. In all of these instances, non2574 dietary ingestion exposures are estimated using residue data from the treated surface 

2575 combined with activity factors for children’s behaviors (e.g., frequency of hand-to-mouth 

2576 contact). Often, EPA models this route and pathway of exposure using inputs from the 

2577 available, and reliable published research. If EPA were to require data to estimate this 

2578 exposure pathway, EPA would require surface residue data, rather than requiring the 

2579 actual monitoring of children or having individual registrants collecting data on 

2580 frequency of hand-to-mouth activities, as these are not chemical-specific. Given the 

2581 unlikelihood of requiring non-dietary ingestion exposure studies, EPA has 

2582 removeddetermined to not finalize this proposed data requirement fromand its 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 104 of 233 

2583 accompanying test note 12 in the final Post-Application Exposure Table as well as the 

2584 accompanying test note 12.in § 158.2270(e).

2585 XIV. Discussion of Key Comments on Environmental Fate Data Requirements 

2586 The following represent the significant comments received on the need for and 

2587 evaluation of environmental fate studies as proposed by EPA. Changes from the 

2588 proposed rule to the final rule are also described. 

2589 A. Need for Environmental Fate Data for Indoor Uses 

2590 1. Comment. Several commenters argued that the proposed environmental fate 

2591 data requirements for indoor uses of antimicrobials should not exceed those in part 158 

2592 for conventional pesticide chemicals, since antimicrobials are not directly broadcast into 

2593 the environment. 

2594 2. EPA’s response. As explained in the proposed rule, there is now a greater 

2595 concern regarding indoor uses of antimicrobials because those antimicrobial uses can 

2596 lead to environmental exposure when they go down -the -drain. The rationale for 

2597 requiring environmental fate data for antimicrobials mirrors that of Unit XI.A. for 

2598 requiring nontarget organism data for antimicrobials. 

2599 There are many uses for which a high potential for exposure exists, and these 

2600 uses may require a more extensive environmental fate data set that could also include 

2601 aerobic and anaerobic metabolism studies. However, such uses will typically require a 

2602 much reduced first tier data set with additional testing triggered if the results of the 

2603 required data indicate a potential risk that needs further characterization. 

2604 B. Transformation Products 

2605 1. Comment. A commenter argued that the Agency has not clearly stated when 

2606 environmental fate data on the transformation products would be required. Additionally, 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 105 of 233 

2607 the commenter also wanted to understand the data that would be required if the 

2608 substance degrades quickly? 

2609 2. EPA’s response. For environmental fate data, the Agency evaluates 

2610 transformation products on a case-by-case basis, using several sources of information. 

2611 First, the transformation products need to be identified. While product chemistry data 

2612 can provide some information on degradates, environmental fate data provide data 

2613 specific to a particular environmental compartment. Environmental fate studies provide 

2614 information on the stability and persistence of the active ingredient and its degradation 

2615 products in the various environmental media. For example, in the hydrolysis study, a 

2616 half-life >30 days indicates that the substance is stable to hydrolytic processes, i.e., the 

2617 substance did not degrade. Similar determinations are made based on the results of 

2618 the photodegradation in soil and water studies, and the aerobic and anaerobic 

2619 metabolism in soil and water studies after review of the required fate data. Monitoring 

2620 and incident data, if available, also may indicate stability and persistence. There could 

2621 also be environmental fate data conducted on a related chemical or information from the 

2622 open literature. This analysis is critical to determining not only the need for 

2623 environmental fate data for transformation products, but also is the first step for 

2624 determining the need for nontarget organism or nontarget plant data for transformation 

2625 products. 

2626 EPA proposed criteria to require testing of transformation/degradation products 

2627 or leachate residues in proposed § 158.2280(a)(2) and (3). To respond to this 

2628 comment, EPA also considered a similar comment on transformation/degradation 

2629 products or leachate residues for nontarget plant and organism testing (see Unit 

2630 XI.B)..). In response to these comments, EPA determined to clarify and revise the 

2631 criteria for testing of transformation/degradation products and leachate residues for 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 106 of 233 

2632 nontarget plant and organisms, and environmental fate, (§ 158.2250(b), 

2633 158.2240(a)(3),) and § 158.2280(a)(2)) to read as follows: 

2634 (2) Data on transformation/degradation products or leachate 

2635 residues of the parent compound are also required to support 

2636 registration, if the Agency determines that the 

2637 transformation/degradation/leachate products meet one of the 

2638 following criteria: 

2639 (i) More toxic, persistent, or bioaccumulative than the parent, 

2640 (ii) Have been shown to cause adverse effects in mammalian or 

2641 aquatic reproductive studies, or 

2642 (iii) The moiety of concern (i.e., functional group in the parent 

2643 chemical molecule that imparts adverse effects) remains intact. 

2644 EPA also determined to clarify and revise the criteria for testing of 

2645 transformation/degradation products and leachate residues for nontarget plant (§ 

2646 158.2250(b)) to read as follows:

2647 (b) Data on transformation/degradation products or leachate residues of the

2648 parent compound are also required to support registration, if the Agency

2649 determines that the transformation/degradation/leachate products meet one of 

2650 the following criteria:

2651 (1) More toxic, persistent, or bioaccumulative than the parent,

2652 (2) Have been shown to cause adverse effects in mammalian or aquatic 

2653 reproductive studies, or

2654 (3) The moiety of concern (i.e., functional group in the parent chemical 

2655 molecule that imparts adverse effects) remains intact.

2656 EPA would use these criteria to determine if environmental fate data on the 

2657 transformation/degradation products or leachate residues are required. Therefore, if the 

2658 environmental fate studies on the parent indicate the transformation product(s) is, for 

2659 example, more persistent in soils, then the same environmental fate data required for 

2660 the parent are required for the transformation product(s). If concerns are identified, then 

2661 higher-tiered environmental fate and/or ecological effects data on the 

2662 transformation/degradation product(s) would be required. 

2663 It should be noted that the criteria for determining whether to assess risks from a 

2664 chemical substance and/or its degradation products when conducting a down -the -drain 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 107 of 233 

2665 analysis are different from those discussed abovepreviously. Those criteria are 

2666 discussed in response to comment 130.4 in the Response to Comments Document in 

2667 the docket at http://www.regulations.gov. 

2668 C. Photodegradation in Soil Study

2669 1. Comment. A commenter claimed that EPA has not sufficiently explained why 

2670 a photodegradation in soil study would be required if a substance hydrolyzes and its 

2671 behavior is known from its soil profile. 

2672 2. EPA’s response. EPA proposed to require the photodegradation in soil study 

2673 for only one use pattern: Wood preservatives. Wood products that have been treated 

2674 with wood preservatives are often in contact with soil, and therefore it is possible for the 

2675 wood preservative chemical, as well as its transformation and degradation products, to 

2676 leach out from the treated wood product. To understand the fate of wood preservative 

2677 chemicals in soil, first requires an understanding of the soils properties. Soil profiles are 

2678 descriptions of soil properties, both physical and chemical. Examples of physical 

2679 characteristics would include: color, bulk density, and texture. Examples of chemical 

2680 characteristics would include: pH of the soil, organic matter content, and Cation 

2681 Exchange Capacity (CEC). Depending on the soil profile, an antimicrobial pesticide can 

2682 undergo chemical and/or biochemical (biodegradation) processes. For example, if the 

2683 pH of the soil is less than 7, the antimicrobial can undergo hydrolysis and become 

2684 nonpersistent, or if the pH of the soil is basic, the antimicrobial could remain stable and 

2685 become persistent. If the organic carbon content of a soil is high, then the soil has a 

2686 high microbial population which facilitates the biodegradation process. Hence the 

2687 nature of a soil (soil profile) is an important indicator of how a pesticide may behave in a 

2688 soil. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 108 of 233 

2689 Many applicants are well aware of soil profiles, since EPA asks for the soil profile 

2690 to be submitted along with the results of the studies in soils. A number of soil profile 

2691 databasesdata bases are available: Two of the databasesdata bases used by OPP are 

2692 one from USDA and one called CLARION. 

2693 In this final rule, EPA has retained the requirement for a photodegradation in soil 

2694 study for the wood preservatives use pattern. The photodegradation in soil study is 

2695 required for all wood preservatives, except for two circumstances. First, if the 

2696 antimicrobial is an inorganic substance or a metal salt, then a photodegradation study 

2697 does not provide applicable information for inorganics and metal salts that do not 

2698 degrade (chemically or biochemically). Second, if data from the standardized soil 

2699 profiles show that the chemical is likely to readily degrade microbially or undergo redox 

2700 reactions (degrade chemically),) to such a degree that there is no formation of 

2701 degradation/transformation/leachate products of concern (as defined in § 

2702 158.2280(a)(2)), then the photodegradation study in soils maystudy would not be 

2703 required. needed. EPA is adding a new test note 10 to replace proposed test note 10 to

2704 has revised the proposed environmental fate table in § 158.2280. Newtest note 10 to 

2705 the Environmental Fate Table, so that the test note 10 to the final Environmental Fate 

2706 Table in § 158.2280(c) explains this conditionthe conditions for not requiring the 

2707 photodegradation in soil study. 

2708 D. Aquatic Sediment Study 

2709 1. Comment. A commenter claimed that EPA is unclear about the triggers that 

2710 would lead to the requirement for an aquatic sediment study, and how down -the -drain

2711 (D-t-D) modeling could affect the need for this study. 

2712 2. EPA’s response. Proposed Test notes 5 and 13 to the proposed 

2713 environmental fate table in § 158.2280 trigger the aquatic sediment study for all use 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 109 of 233 

2714 patterns except the aquatic areas use pattern. EPA has re-evaluated the need for the 

2715 aquatic sediment study and the appropriate triggers. EPA agrees that having two 

2716 triggers, both of which use a weight-of-evidence evaluation process, is confusing, and 

2717 believes that one trigger (proposed test note 13) would be sufficient for triggering the 

2718 aquatic sediment study. In today’s actionthis final rule, EPA is removing test note 5 

2719 from the test note column for the aquatic sediment study data requirement. Based on 

2720 this re-evaluation, EPA also believes that the aquatic sediment study should be required 

2721 for the antifoulant coatings and paints use pattern since an antifoulant use would meet 

2722 the criteria of the trigger in test note 13, which is: “...data are required based on the 

2723 potential for aquatic exposure and if the weight-of-evidence indicates that the active 

2724 ingredient or principal transformation products are likely to have the potential for 

2725 persistence, mobility, nontarget aquatic toxicity, or bioaccumulation.” Antifoulants are 

2726 released/applied directly to the aquatic environment. These products are often 

2727 manufactured to be persistent, and because of the continuous release process, some of 

2728 the active ingredient is likely to be transferred to the bottom of the water column and 

2729 then be adsorbed to the sediment. This is likely to result in adverse effects on nontarget 

2730 benthic organisms. Since this meets the triggers for requiring the study, todayin this 

2731 final rule EPA is changing the “CR” for the aquatic sediment study for the antifoulant 

2732 coatings and paints use pattern to “R.” 

2733 The aquatic sediment study provides information about the 

2734 degradation/dissipation processes under field conditions. The results of D-t-Ddown the 

2735 drain modeling are unlikely to provide appropriate information to determine the need for 

2736 the aquatic sediment study. The current version of the D-t-Ddown the drain model 

2737 estimates concentrations of chemical substances in the water column downstream of 

2738 wastewater treatment facilities, but does not estimate concentrations in the sediment. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 110 of 233 

2739 G. Monitoring of Representative U.S. Waters Study.

2740 1. Comment. The commenter noted that there is no guidance on how to conduct 

2741 a “monitoring of representative USU.S. waters” study, and that EPA has not provided 

2742 the criteria for triggering a “monitoring of representative U.S. waters” study. 

2743 2. EPA’s response. The commenter is correct: EPA does not have a guideline 

2744 for conducting this study. For all pesticides, such monitoring (studies) of representative 

2745 U.S. waters is a very rare occurrence. If EPA were to require such a monitoring study, 

2746 protocols would have to be developed to specify a great deal of information: 

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

2748 monitoring occur? 

2749  Is the sampling for ground water, surface water, or the estuarine/marine 

2750 environment? 

2751  Which chemical substances would be monitored? Is just the antimicrobial 

2752 (parent) to be analyzed, or would the transformation/degradation products also be 

2753 analyzed? Such a protocol would be specific to a particular pesticide, where that 

2754 pesticide is used, and where the pesticide has been detected, and could not necessarily 

2755 be used for a different pesticide. 

2756 For the monitoring of representative U.S. waters data requirement, the term 

2757 “residue of concern” (ROC) is currently specified in the Environmental Fate Data 

2758 Requirements Table in the test substance to support column. Since the ROC would be 

2759 determined during protocol development, EPA is adding this information as part of a 

2760 new test note 17 to the final Environmental Fate Table in § 158.2280. 

2761 As stated in the preamble to the proposed rule, a WOE approach would be used 

2762 to determine if a monitoring of representative U.S. waters study should be required. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 111 of 233 

2763 The preamble to the proposed rule discusses this aspect in more detail (73 FR 59413). 

2764 EPA expects this study to be rarely required. 

2765 H. AWPA and ASTM Methods 

2766 1. Comment. A commenter argued that AWPA method E11-97 or E20-04, and 

2767 ASTM Method D5108-90 “are of limited or no relevance to estimating environmental 

2768 exposures” for wood preservatives, or antifoulants, respectively. According to the 

2769 commenter, the results of the ASTM method are not suitable for “estimating release 

2770 rates for regulation purposes.” The commenter believes that both methods 

2771 “overestimate leach rates and are not intended for use in risk assessments.” The 

2772 commenter also provided information to indicate that ASTM Method D5108-90 has been 

2773 replaced by ASTM D6442-06. 

2774 2. EPA’s response. Proposed Test note 15 to the proposed environmental fate 

2775 table in § 158.2280 triggers the special leaching data requirement for the wood 

2776 preservative use pattern. EPA’s intent in specifying that it would accept an ASTM or 

2777 AWPA method was to allow applicants to use these readily available protocols. 

2778 However, as noted in the proposed testnotetest note, protocol review was still required 

2779 for some of these methods. Since the commenters believe that these AWPA methods 

2780 are inappropriate, but have not offered alternative methods, test note 15 to the final 

2781 Environmental Fate Table in § 158.2280(c) is revised to remove the AWPA methods. 

2782 Test note 12 to the final Environmental Fate Table in § 158.2280(c) is added to require 

2783 protocol review. 

2784 Test note 16 to the proposed environmental fate table in § 158.2280 triggers the 

2785 special leaching data requirement for the antifoulant coatings and paints. Since the 

2786 commenter indicated that the ASTM method has been replaced, EPA believes that 

2787 specifying an ASTM method number in regulatory text may provide insufficient clarity, at 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 112 of 233 

2788 some point in the future. Therefore, test note 16 to the final Environmental Fate Table 

2789 in § 158.2280 is revised to remove the ASTM methods. Test note 12 to the final 

2790 Environmental Fate Table in § 158.2280(c) is added to require protocol review. 

2791 XV. Discussion of Key Comments on Down -the -Drain Analysis 

2792 The following represent the significant comments received on the need for and 

2793 performance of a down -the -drain analysis as proposed by EPA. Changes from the 

2794 proposed rule to the final rule are also described.

2795 A. Changes to Down -the -Drain Analysis Based on Comments Received 

2796 1. Comment. Some commenters expressed concern regarding EPA’s proposal 

2797 to exclude antifoulants and wood preservatives from testing designed to protect POTWs 

2798 and the aquatic environment. These commenters contend that these compounds may 

2799 reach POTWs through sources such as hull blast water, landfill leachate, and 

2800 centralized waste treatment facilities. They think EPA should revisit this assumption to 

2801 verify its accuracy. 

2802 2. EPA’s response. Based on this comment, EPA did re-evaluate its original 

2803 determination to exclude antifoulant coating and paints, wood preservatives, and 

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

2805 exclude aquatic areas from a down -the -drain analysis. As discussed in the preamble

2806 to the proposed rule (73 FR 59390) aquatic areas include lakes, ponds, streams, 

2807 drainage ditches, and other bodies of water. These would not be expected to result in 

2808 down -the -drain releases and are therefore unlikely to be discharged to a WWTP. 

2809 Based on its re-evaluation, EPA believes that a down -the -drain analysis is 

2810 needed for the wood preservative, and antifoulant paints and coatings use patterns, as 

2811 well as the all other use patterns category. There are a number of sources of indirect 

2812 releases of antifoulants and wood preservatives to surface water via WWTPs. The 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 113 of 233 

2813 Emission Scenario Document (ESD) for Wood Preservatives, which is part of the OECD 

2814 Series on Emission Scenario Documents, documents numerous sources of 

2815 environmental releases directly to surface water. The ESD also describes various types 

2816 of wood preservative facilities where there may be environmental releases to the facility 

2817 drain that subsequently drains to a WWTP. Some of the types of wood preservative 

2818 facilities identified in the OECD ESD for wood preservatives include automated spraying 

2819 plants, dipping/immersion plants, and plants that employ vacuum-pressure and double 

2820 vacuum processes. According to this OECD ESD for wood preservatives, it is also 

2821 possible for releases to sewage treatment plants to occur from some treated wood 

2822 products, such as noise barriers. 

2823 According to the OECD Emission Scenario Document(ESD) for Antifouling 

2824 Products, in addition to the numerous sources of direct environmental releases to 

2825 surface water resulting from the use of antifoulant paints and coatings, there is the 

2826 potential for antifoulants to enter sewage treatment plants as a result of application and 

2827 removal of antifoulant paints at boatyards and marinas. 

2828 Thus, OPP’s Antimicrobial Division (AD) will perform a down -the -drain 

2829 assessment for every product with an applicable use or exposure scenario that has the 

2830 potential for waters containing antimicrobials to reach a WWTP. To perform this 

2831 assessment, the Agency is requiring data on the biodegradation of an antimicrobial 

2832 pesticide and its potential toxicity to WWTP microorganisms in an activated sludge 

2833 basin. For some antimicrobial pesticides, the Agency will also require the activated 

2834 sludge sorption isotherm test to determine removal from wastewater via partitioning to 

2835 activated sludge. For additional information on the changes made to the proposed 

2836 environmental fate data requirements table see response to comment 134.1 in the 

2837 Response to Comments Document in the docket at http://www.regulations.gov.
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 114 of 233 

2838 B. Use of E-FAST Model 

2839 1. Comment. According to one commenter, EPA staff indicated at the part 158, 

2840 subpart W Antimicrobials Data Requirements Workshop held on November 6, 2008 that 

2841 the E-FAST model may have been based on municipal WWTPs that received only 

2842 “residential” discharges. The commenter suggested that is very unlikely and stated that 

2843 according to the E-FAST manual, the model was based on data from actual U.S. 

2844 municipal WWTPs. Nearly every municipal WWTP receives discharges from many 

2845 types of non-residential sources, like commercial facilities, medical facilities, institutions, 

2846 and cooling water systems (which are common in commercial buildings). Even in 

2847 smaller communities, POTWs receive wastewater from residential and commercial 

2848 (e.g., schools, stores, restaurants, hotels/motels, and/or medical facilities) sources. 

2849 Most municipal WWTPs also receive both process and non-process discharges from 

2850 industrial facilities. Some commenters contend that the E-FAST model is applicable as 

2851 a screening-level model for all antimicrobial use patterns with discharges that are 

2852 typically rinsed down -the -drain including agricultural premises and equipment, food 

2853 handling/storage establishments, residential and public access premises, medical 

2854 premises and equipment, industrial processes and water systems, swimming pools, and 

2855 others. 

2856 2. EPA’s response. The E-FAST documentation manual indicates that the down 

2857 -the -drain module was developed as a screening-level model for estimating 

2858 concentrations of chemicals in surface water that may result from the disposal of 

2859 consumer products into household wastewater. The model developers have confirmed, 

2860 however, that the databasedata base of WWTPs that is accessed by this module 

2861 consists of domestic WWTPs that receive wastewaters predominantly from residential, 

2862 commercial, and institutional sources, and not solely from residential sources. In 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 115 of 233 

2863 modeling releases of antimicrobial pesticides to environmental media, the appropriate 

2864 data inputs, methods, and tools are dependent upon the source of the environmental 

2865 releases. To assess exposures and risks to releases of antimicrobial pesticides to 

2866 surface water from residential, commercial, and institutional sources, the down -the -

2867 drain module of E-FAST is the most appropriate tool. 

2868 To assess exposures and risks to antimicrobial pesticides from manufacturing, 

2869 processing, and industrial use facilities, the general population and ecological 

2870 exposures from the industrial releases module of E-FAST is the most appropriate tool. 

2871 The decision to use the general population and ecological exposures from the industrial 

2872 releases module is made on a case-by-case basis considering the availability of data 

2873 required as inputs to the module, and the potential for significant exposure. For 

2874 example, a low volume use may not require use of this module. 

2875 EPA agrees that the E-FAST model is applicable as a screening-level model for 

2876 all antimicrobial use patterns with discharges that are typically rinsed down -the -drain,

2877 including agricultural premises and equipment, food handling/storage establishments, 

2878 residential and public access premises, medical premises and equipment, industrial 

2879 processes and water systems, swimming pools, and others. 

2880 C. Exceedance Levels

2881 1. Comment. Some commenters questioned the justification for the following 

2882 exceedance levels that were used by EPA to evaluate potential risks to aquatic 

2883 organisms: 

2884 i. Potential risks from effects to aquatic invertebrates and fish: Exceedance of 

2885 the chronic concentration of concern (COC) for 20 or more days triggers a potential for 

2886 concern; 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 116 of 233 

2887 ii. Potential risks from effects to aquatic invertebrates and fish: Exceedance of 

2888 the acute COC for 4 or more days triggers a potential for concern; and 

2889 iii. Potential risks from effects to algae: Exceedance of the COC for algae for 4 

2890 days or less may trigger a concern and is evaluated on a case-by-case basis. 

2891 2. EPA’s response. These Exceedance levels and corresponding number of 

2892 days of exceedance that trigger potential for concern are those cited on page 7-7 of 

2893 EPA/OPPTS/OPPT’s “Revised Draft New Chemicals Decision Guidelines Manual” 

2894 dated April 17, 2001.in EPA/OPPTS/OPPT's "Interpretive Assistance for Sustainable 

2895 Futures Summary Assessment", last updated August, 2011. The justification that the 

2896 potential for chronic risk to aquatic organisms may exist if the predicted environmental 

2897 concentration (PEC) exceeds the chronic COC and the exceedance occurs for 20 days 

2898 or more per year is documented on page 11 of “Interpretive Assistance for Sustainable 

2899 Futures Summary Assessment,” updated January 22, 2007: 

2900 “...although there is a"The potential for chronic risk to aquatic organisms may 

2901 exist ONLY if the PEC exceeds the chronic COC for 20 days or more per year. If 

2902 exposure occurs for 20 days of more per year, the concentration of the chemical 

2903 in thesurface water tomay reach levels exceeding the hazardous level, the levels 

2904 are not exceeded for a sufficient duration of time to induce anyassociated with

2905 chronic effects. (Lynch et al., 1994). The 20-day criterion is derived from partial 

2906 life-cycle tests (Daphnid chronic and fish early life-stage tests) that typically 

2907 range from 21 to 2829 days in duration. Low concentration for chronic risk exists 

2908 if the COC is exceeded on fewer than 20 days per year or the PEC is less than 

2909 the chronic COC.”."

2910 The justification for the potential for acute risks to aquatic organisms appears on 

2911 page 12: 

2912 "The potential for acute risk to aquatic organisms exists if the predicted 

2913 environmental concentration (PEC) is greater than the acute concentration of 

2914 concern (COC).

2915 If Acute COC > PEC: Low concern for risk

2916 If Acute COC < PEC: Potential for risk" 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 117 of 233 

2917 EPA notes that risk is influenced by both the duration of exposure and the 

2918 likelihood of that exposure occurring. Often mathematical models are used to estimate 

2919 exposures and risks. There are two types of models: Deterministic or probabilistic. 

2920 Probabilistic modeling is a technique that utilizes the entire range of input data to 

2921 develop a probability distribution of risk or exposure rather than a single point value. 

2922 The analysis identifies the probability that the exposure exceeds the COC and for what 

2923 timeframe. Deterministic modeling is based on select input data that result in a single 

2924 point estimate. The estimate either exceeds or does not exceed the COC. Models 

2925 such as E-FAST have the capability of providing either deterministic or probabilistic 

2926 results. Consequently, criteria for determining whether or not testing on aquatic 

2927 organisms is required need to take into account the possibility that the estimated 

2928 exposure could be modeled using either deterministic or probabilistic modeling. 

2929 Therefore, two test notes to the final Nontarget Organism Table in § 158.2250 have 

2930 been revised to include a probabilistic trigger for down -the -drain analyses, while 

2931 retaining the existing deterministic trigger for releases of antimicrobials that are 

2932 expected to enter WWTPs. Test note 7 to the final Nontarget Organism Table in § 

2933 158.2250(c) triggers the acute freshwater invertebrate toxicity study (TEP testing) and 

2934 the acute freshwater fish toxicity study (TEP testing). Test note 12 to the final Nontarget 

2935 Organism Table in § 158.2250(c) triggers the fish life-cycle study.

2936 D. Evaluation of Discharges to Still Water and to Salt Water 

2937 1. Comment. During the Antimicrobial Data Requirements Workshop held on 

2938 November 6, 2008, EPA staff indicated that evaluation of discharges to still water and to 

2939 salt water would be challenging. The commenter’s argued that the E-FAST model 

2940 manual suggests that these discharges can be readily evaluated with appropriate input 

2941 data and elimination of the PDM (Probabilistic Dilution Model) option. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 118 of 233 

2942 2. EPA’s response. EPA believes that the commenter misunderstood the 

2943 context of the Information provided by EPA staff both in the proposed rule and at the 

2944 presentation on November 6, 2008. E-FAST has two modules for estimating releases 

2945 to surface water: The down -the -drain module, and the general population and 

2946 ecological exposure from industrial releases module. 

2947 When the down -the -drain module of E-FAST is run without the PDM option, the 

2948 results are limited to estimates of concentrations in surface water downstream of 

2949 domestic wastewater treatment facilities. The down -the -drain module has no option 

2950 for estimating concentrations in non-flowing waterbodies such as lakes, bays, estuaries, 

2951 and oceans. The discussion at the November 6, 2008, Workshop focused solely on the 

2952 down -the -drain module. 

2953 E-FAST, however, has the capability for evaluating discharges to still water and 

2954 to salt water from discharges to WWTPs that receive manufacturing, processing, and 

2955 industrial use releases, but not from discharges to surface water via domestic WWTPs. 

2956 The general population and ecological exposure from industrial releases module is 

2957 designed to estimate releases to air, water, and land from manufacturing, processing, 

2958 and industrial use of chemical substances. The databasedata base for estimating 

2959 releases to WWTPs that primarily receive wastewater from manufacturing, processing, 

2960 and industrial uses requires estimates of releases to environmental media from models 

2961 such as ChemSTEER (Chemical Screening Tool for Exposures and Environmental 

2962 Releases), a model developed by EPA’s OPPT or from data and calculations included 

2963 in standard scenarios, also developed by OPPT 

2964 (www.epa.gov/oppt/exposure/pubs/chemsteerdl.htm). The general population and 

2965 ecological exposure from industrial releases module includes an option for estimating 

2966 concentrations in lakes, bays, estuaries, and oceans. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 119 of 233 

2967 E. Parameters for Down -the -Drain Analysis 

2968 1. Comment. Several commenter’s argued that EPA’s approach for down -the -

2969 drain chemicals separates the exposure and the effects of the assessment and subjects 

2970 chemicals to similar testing requirements regardless of the mass of chemicals disposed 

2971 of in the environment. According to these commenters, the fact that EPA does not 

2972 guide testing by the extent of environmental exposure is wasteful for ingredients which 

2973 will reach the environment at low levels. Even for chemicals which are used at greater 

2974 volume, the commenters claimed that there is no proof that EPA’s program will achieve 

2975 its goal without being wasteful and some commenters believe that EPA’s approach will 

2976 likely result in significant unwarranted costs in animals, time, and dollars. The 

2977 commenters asserted that this will result in unnecessary loss of animals, increased 

2978 costs to the consumer and will negatively affect product innovation as new product 

2979 development will be slowed due to the extra regulatory burden. The benefit to the 

2980 environment of the EPA approach, according to the commenters, is likely to be small 

2981 and not commensurate with its costs. 

2982 2. EPA’s response. EPA disagrees with this comment. Three key input 

2983 parameters for the down -the -drain model are: 

2984 i. Percent removal of antimicrobial pesticide during wastewater treatment; 

2985 ii. Concentrations of concern for antimicrobial pesticides based on acute and 

2986 chronic end-points for freshwater fish, freshwater invertebrates, and freshwater plants; 

2987 and 

2988 iii. Wastewater treatment plant influent volume of antimicrobial pesticide. 

2989 As demonstrated in the sensitivity analysis of the down -the -drain model in the 

2990 document, “Four Case Studies of Antimicrobial Pesticides in the Down-the-Drain 

2991 Screening Model, Using the Proposed Approach for a Screening-Level Environmental 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 120 of 233 

2992 Fate Assessment” (availableidentified in the docket at http://www.regulations.govby 

2993 document ID number EPA-HQ-OPP-2008-0110-0044), the amount of chemical 

2994 disposed in the environment strongly influences the results of the down -the -drain 

2995 model. It is possible that if the amount of chemical disposed is small (i.e., WWTP 

2996 influent volume is low and/or high percent removal during wastewater treatment), that 

2997 the predicted surface water concentration of the antimicrobial, even for a chemical of 

2998 high toxicity, would not exceed the Agency’s level of concern. Under such 

2999 circumstances, higher-tier testing (environmental fate, ecotoxicity, and plant protection) 

3000 is unlikely to be triggered. Since, higher-tier testing is triggered only if the down -the -

3001 drain model indicates that the predicted concentration of the antimicrobial may 

3002 adversely affect aquatic organisms this reduces the number of tests required, and 

3003 therefore the animals, time, and dollars. 

3004 EPA also notes that two of the three key input parameters needed to run the 

3005 down -the -drain model, percent removal during wastewater treatment and wastewater 

3006 treatment plant influent volume do not involve animal testing and would not lead to loss 

3007 of animals. Fate tests required to determine removal during wastewater treatment via 

3008 biodegradation and adsorption are inexpensive. No costs are associated with 

3009 wastewater treatment planWWTP influent volume. 

3010 F. Acute and Chronic Toxicity Endpoints 

3011 1. Comment. At the Antimicrobial Data Requirements Workshop held on 

3012 November 6, 2008, EPA staff indicated that chronic aquatic toxicity endpoints might not 

3013 be used to evaluate antimicrobial discharges from municipal WWTPs. A commenter 

3014 argued that since EPA/OW requires municipal WWTPs to conduct both acute and 

3015 chronic toxicity tests regularly as conditions of CWA-regulated National Pollution 

3016 Discharge Elimination System (NPDES) permits, both acute and chronic endpoints 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 121 of 233 

3017 should be evaluated by EPA/OPP to ensure that antimicrobial discharges will not cause 

3018 toxicity in municipal WWTP effluent. 

3019 2. EPA’s response. To assess whether the proposed screening level 

3020 assessment and tiered system of data requirements provides the data needed to 

3021 assess exposure and risk of antimicrobial pesticides released to the environment via 

3022 down -the -drain use patterns, the Agency conducted four case studies (73 FR 59408-

3023 9). Based on this comment, EPA has re-evaluated the approach used for the case 

3024 studies, in which the higher-tiered data was triggered based on the results of the 

3025 available data. To ensure that antimicrobial discharges will not cause toxicity to aquatic 

3026 organisms downstream of WWTP effluents requires an evaluation of both acute and 

3027 chronic toxicity endpoints. This means that the chronic ecotoxicity data needs to be 

3028 submitted at the same time as the acute ecotoxicity data, so both types of studies are 

3029 available for EPA to use for the ecological risk assessment. Also see Units XV.A and B. 

3030 Consequently, in the final Nontarget Organism Table in § 158.2250(c), the table 

3031 descriptors for the fish early-life stage and aquatic invertebrate life cycle tests have 

3032 been changed from “CR” to “R” for the wood preservatives use pattern and the all other 

3033 use patterns category. Test note 10 to the final Nontarget Organism Table in § 

3034 158.2250(c) has been modified to remove the trigger since it is no longer needed. 

3035 XVI. Discussion of Key Comments on Residue Chemistry Data Requirements

3036 The following represent the significant comments received on the need for and 

3037 evaluation of residue chemistry studies as proposed by EPA. Changes from the 

3038 proposed rule to the final rule are also described. 

3039 A. Scope of the Residue Chemistry Data Requirements 

3040 1. Comment. Several commenters found the scope of coverage of the residue 

3041 data requirements in § 158.2290(b) to be vague and confusing. Further, the ACC 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 122 of 233 

3042 Biocides Panel asserted that this section required data for uses for which a FFDCA 

3043 section 408 tolerance is not required and over which, therefore, EPA allegedly has no 

3044 jurisdiction. 

3045 2. EPA’s response. EPA is clarifying § 158.2290(b) which pertains to the scope 

3046 of the residue data requirements. That section can be read as limiting the residue 

3047 chemistry data requirements to pesticide products requiring a tolerance or tolerance 

3048 exemption. This apparent limitation is inconsistent with both the preamble’s general 

3049 description of the scope this subpart W and the preamble’s description of the scope of 

3050 the residue data requirements section, and is internally inconsistent with the terms of § 

3051 158.2290(b). Various commentators noted the lack of clarity in this portion of the rule. 

3052 The preamble’s general discussion of the scope of subpart W made clear that 

3053 this subpart was not limited to “antimicrobial pesticides” as defined by FIFRA section 

3054 2(mm) – which excluded antimicrobial pesticide uses subject to either FFDCA section 

3055 408 or section 409 – but extended to among other things, “[p]esticide products for 

3056 antimicrobial use in/on food” (73 FR 59385). In no way, however, did this discussion 

3057 suggest or imply that the subpart is limited to antimicrobial uses requiring FFDCA 

3058 section 408 tolerances or exemptions from tolerances. To the contrary, the preamble’s 

3059 discussion of toxicity data requirements expressly notes that data are needed under 

3060 subpart W to assess dietary risk whether or not a section 408 tolerance is required. The 

3061 preamble specifically states that, although certain antimicrobial food uses are regulated 

3062 under the FFDCA by FDA under section 409 and not section 408, EPA still needs data 

3063 on these uses to assess dietary risk to fulfill its statutory obligations under FIFRA 

3064 section 2(bb)(2), which establishes the FFDCA section 408 safety standard as a 

3065 component of the FIFRA standard for registration/cancellation for FIFRA pesticide uses 

3066 that result in residues on food (73 FR 59394). Further, the preamble’s discussion of 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 123 of 233 

3067 residue chemistry data requirements states that these data are needed for “direct and 

3068 indirect food uses” including application to “food or water” both to assess risk and for 

3069 tolerance-setting purposes (73 FR 59401: “In addition to dietary risk assessments, 

3070 residue chemistry data are used to establish pesticide tolerance . . . .”). Finally, both the 

3071 preamble’s discussion of residue data requirements and the relevant rule text mention 

3072 antimicrobial uses that would be excluded by a limitation of the rule to antimicrobial 

3073 uses requiring tolerances. For example, both the preamble and rule text refer to “fruit 

3074 and vegetable rinses,” antimicrobials “incorporated into a material that may contact food 

3075 or feed,” and “[a]quatic uses that have the potential to result in residues in potable 

3076 water” and the fact that all of these uses may not need section 408 tolerances (73 FR 

3077 59401 and 59444). 

3078 Accordingly, EPA is revising § 158.2290(b) to make clear it is not limited to 

3079 antimicrobial uses which need FFDCA section 408 tolerances. With some 

3080 modifications, EPA is retaining in § 158.2290(b) a non-exclusive list identifying 

3081 examples of antimicrobial products covered by this section. This revision to § 

3082 158.2290(b) makes clear that the residue data requirements apply to antimicrobial 

3083 products that may result in residues in food or water whether or not a FFDCA section 

3084 408 tolerance is needed. Section 158.2290(b) is revised by replacing the opening 

3085 linesintroductory text of subsectionparagraph (b)(1) with the following: 

3086 “Residue chemistry data are required for: 

3087 “ (1) Antimicrobial end-use products with uses that may result in residues

3088 in or on food including, but not limited to:” 

3089 The first item in the list of covered uses now reads “Products that require a 

3090 tolerance, tolerance exemption, or food additive regulation or clearance.” The insertion 

3091 of the reference to food additive regulations and clearances is consistent with the rule’s 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 124 of 233 

3092 scope which is not limited to pesticide uses regulated under FFDCA section 408. 

3093 Additionally, each of the subparagraphs listing examples of covered uses has been 

3094 revised to refer to “products” rather than “uses” for consistency and clarity. Although the 

3095 subparagraphs are overlapping (i.e., a product may fall in more than one paragraph), 

3096 the revised subsection now clarifies the overall scope of thisthe section. These 

3097 revisions make § 158.2290(b) consistent with the scope of the rule described in the 

3098 preamble and the scope of the toxicology data requirements. 

3099 Not only are these changes consistent with the scope of the rule as discussed in 

3100 the preamble (i.e. data requirements are not limited to uses needing section 408 

3101 tolerances) but the revised language’s focus on whether use of a pesticide may result in 

3102 residues in or on food follows directly from the intent of the residue chemistry 

3103 requirements as discussed in the preamble. There, EPA explained that the proposed 

3104 requirements will provide information “to better estimate human dietary exposure to 

3105 antimicrobial residues in or on food or feed,” “to determine the composition of the 

3106 pesticide residue and how much of the residue is present in food or animal feed,” and to 

3107 “measure how much of the residue of concern is present in food, feed, and water” (73 

3108 FR 59401). Further, the revised language is consistent with the scope of FFDCA 

3109 section 408 (applies to “pesticide chemical residue[s] in or on food”) and FIFRA 

3110 (requires consideration of “residues that result from the use of a pesticide in or on 

3111 food”). It also follows directly from the existing data requirements applying to 

3112 antimicrobials in part 161. Those regulations provide that “Residue Chemistry Data are 

3113 used by the Agency to estimate the exposure of the general population to pesticide 

3114 residues in food and for setting and enforcing tolerances for pesticide residues in food 

3115 or feed.” 40 CFR 161.202(c)(1); see also 40 CFR 161.202(c)(2) (“results of tests on the 

3116 amount of residues remaining on or in the treated food or feed are needed to support a 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 125 of 233 

3117 finding as to the magnitude and identity of residue which result in food or animal feed as 

3118 a consequence of a proposed pesticide usage”); 40 CFR 161.240(b)(14) (Residue data 

3119 on indoor use of pesticide “if such a use could result in residues in food or feed”). 

3120 Finally, the revised language also tracks EPA’s requirements for residue chemistry data 

3121 under the current data requirements for conventional pesticides in 40 CFR part 158, 

3122 subpart O. In the preamble to the proposed rule, EPA explained that the residue data 

3123 requirements for antimicrobials were adapted from the conventional data requirements 

3124 in subpart O (73 FR 59401). For uses of conventional pesticides, other than uses in 

3125 agriculture, part 158 states that “[residue chemistry] [d]ata may be required . . . if 

3126 residues may occur in food or feed as a result of the use.” (40 CFR 158.1410(a)(2)). 

3127 The regulation also makes clear that this requirement applies whether or not a tolerance 

3128 is needed under FFDCA section 408. The regulation specifies that “most products used 

3129 in or near kitchens require residue data for risk assessment purposes even though 

3130 tolerances may not be necessary in all cases.” (Id.) 

3131 The commenters’ concern that the residue chemistry requirements exceeded 

3132 EPA’s jurisdiction under the FFDCA is addressed above in Unit IV. 

3133 B. Complete Transference of the Antimicrobial into Food 

3134 1. Comment. The commenter believes that additional clarification is needed 

3135 concerning EPA’s statement, “in the absence of data [the Agency will] evaluate the 

3136 need for a tolerance or tolerance exemption by assuming complete transference of the 

3137 chemical into food over the lifetime of the treated product.” 

3138 2. EPA’s response. Complete transference refers to an assumption that the 

3139 Agency would initially make regarding the migration of antimicrobial residues from an 

3140 impregnated food contact material to the food contacting that material over the typical 

3141 use life of the antimicrobial-impregnated material. The worst-case assumption is that 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 126 of 233 

3142 100 percent of the antimicrobial residues resulting from use at the maximum registered 

3143 rate transfers into the food, which is then used to estimate a conservative dietary 

3144 exposure. If the aggregate risk calculated using this conservative assumption, from use 

3145 of the antimicrobial in question, is less than EPA’s level of concern, then no measured 

3146 data are needed. If the aggregate risk meets or exceeds EPA’s level of concern, then 

3147 chemical-specific data quantifying residue migration to refine this dietary exposure 

3148 component may be required. To refine the exposure, the applicant may choose to 

3149 perform one or more of the FDA protocols to estimate migration rate into food simulants 

3150 (FDA/CFSAN, 2007, Preparation of Premarket Submissions for Food Contact 

3151 Substances: Chemistry Recommendations (Ref. 11 to the proposed rule, in the docket

3152 at http://www.regulations.gov)).stimulants (see document ID number EPA-HQ-OPP3153 2008-0110-0013). Alternatively, or subsequently, the applicant may choose to conduct 

3154 a chemical-specific nature of the residue on surfaces study and a migration study 

3155 investigating actual impregnated materials using representative foods. 

3156 C. Alternative Formats for Residue Chemistry Data Requirements Table Suggested by 

3157 Commenters

3158 1. Comment. Two different commenters suggested two different options as 

3159 alternative approaches to the antimicrobial residue chemistry data requirement table 

3160 proposed by EPA. One of the commenters separated the residue chemistry data 

3161 requirements into two tables, referred to as Part 1 and 2 [(ACC comment, identified in 

3162 the docket at http://www.regulations.gov;by document ID number EPA-HQ-OPP-2008-

3163 0110-0088.10, p. 7].). The other commenter suggested a single table format [(CSPA 

3164 Comment, identified in the docket at http://www.regulations.gov;by document ID number 

3165 EPA-HQ-OPP-2008-0110-0086.2].).
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 127 of 233 

3166 2. EPA’s response. All three of the commenter-suggested tables had the same 

3167 five “Supporting Information” studies as the first section of the table proposed by EPA, 

3168 but with various mixtures of “R,” “CR,” and “NR.” In the final rule, EPA has retained the 

3169 same Supporting Information of the first section of the Residue Chemistry Table as 

3170 proposed. However, EPA has adopted the commenters’ suggestion for a tiered format

3171 in the last two sections of the Residue Chemistry Table. After review, EPA believes the 

3172 commenters’ suggested tiered approach is more suitable to antimicrobials than that 

3173 proposed by EPA. All three commenterof the commenters’ tables suggested that Tier 1 

3174 consist of a “Screening-level dietary exposure assessment.” Although an applicant may 

3175 opt to conduct a dietary exposure assessment, EPA does not consider this to be a data 

3176 requirement. Applicants often conduct a dietary exposure assessment to understand 

3177 the dietary risks before submitting an application to EPA. If submitted, EPA would 

3178 review the assumptions used by the applicant and compare them to EPA’s modeling. If 

3179 the applicant’s modeling indicates that dietary risk is likely to meet or exceed the 

3180 Agency’s level(s) of concern, the applicant may decide to continue on to Tier 2 or 3. 

3181 Therefore, EPA has not added a requirement to conduct a dietary exposure 

3182 assessment. 

3183 Both the Part 1 Table and the single table suggested that Tier 2 consist of a 

3184 “Refined dietary exposure assessment.” As is the case for the commenter’s suggested 

3185 Tier 1 “Screening-level dietary exposure assessment,” this is optional for the applicant; 

3186 therefore, EPA has not added a requirement to conduct a refined dietary exposure 

3187 assessment. 

3188 Both the Part 1 Table and the single table suggested that Tier 3 consist of nature 

3189 of residue on surface, bioaccumulation, magnitude of residue, residue analytical 

3190 method, and storage stability. These are each addressed individually belowas follows: 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 128 of 233 

3191 i. Nature of residue on surface. The Agency agrees that this study is applicable 

3192 and a valuable addition to the data set necessary to support registration and risk 

3193 assessment of antimicrobial uses on/in food-contact surfaces and impregnated 

3194 materials (treated articles). EPA has added this study intoto the final Residue 

3195 Chemistry Data Requirements Table in part 158, subpart W. 

3196 ii. Bioaccumulation. EPA believes that the commenters intended that this study 

3197 apply only to fish and that the bioaccumulation study required for ecological effects 

3198 should substitute for the nature of the residue on surface study for aquatic uses or 

3199 indoor/outdoor raw agricultural commodity uses. EPA has found that the fish 

3200 bioaccumulation study is often not useful for residue chemistry purposes because 

3201 characterization of fish residues is only required if the bioconcentration (of total 

3202 residues) factor is > 10001,000. The fish bioaccumulation study has not been adopted 

3203 by EPA for residue chemistry. Of much more use to residue chemistry and retained in 

3204 this final rule, are the fish metabolism and magnitude of the residue studies in fish 

3205 described in OPPTS Guideline 860.1400. 

3206 iii. Magnitude of residue (MOR). Commenters proposed this study by the very 

3207 general title “Magnitude of residue.” EPA considers MOR to be any study designed to 

3208 quantify “how much” of the residues of concern will result in food, on surfaces, in water, 

3209 etc., following use of an antimicrobial according to label directions. The commenters 

3210 stated in a footnote to this study that, in the case of food-contact sanitizers and treated 

3211 articles, MOR would consist of a migration study. Because food-contact sanitizer and 

3212 treated article uses comprise at least 80 percent of all antimicrobial food uses, EPA has 

3213 retained the migration study and the food-handling study by name but has moved them 

3214 to a different tier. All the remaining proposed types of MOR studies are much more 

3215 rarely required due to characteristics such as the use pattern and/or physicochemical 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 129 of 233 

3216 properties of the antimicrobial in question. For that reason, the following have been 

3217 grouped as “Higher tiered” studies in the final rule: Nature of the residue in plants, 

3218 nature of the residue in livestock, residue analytical methods for tolerance enforcement, 

3219 multiresidue method testing, potable water, fish, irrigated crops, meat/milk/poultry/eggs, 

3220 crop field trials, processed food or feed, and anticipated residues. 

3221 iv. Residue analytical method. EPA agrees with the commenters that an 

3222 analytical method for data collection is required whenever magnitude of the residue 

3223 studies are required. The Agency has retained this study in the final Residue Chemistry 

3224 Table. 

3225 v. Storage stability. EPA agrees with the commenters that storage stability data 

3226 are required whenever magnitude of the residue studies are required. The Agency has 

3227 retained this study in the final Residue Chemistry Table. 

3228 The Part 2 Table did not recommend requiring a Refined Dietary Exposure 

3229 Assessment. Rather, its Tier 2 consists of studies entitled nature of the residue in 

3230 commodity, nature of the residue in livestock, residue analytical methods for 

3231 enforcement of tolerances, multiresidue analytical method, magnitude of the residue: in 

3232 commodities, in water, and in meat/milk/poultry/eggs, storage stability, and anticipated 

3233 residues. EPA agrees that all of these studies should be required and has retained all 

3234 of them in the highest tier in the final Residue Chemistry Table. Note that two of the 

3235 commenter-suggested studies (nature of the residue in commodity and magnitude of 

3236 the residue in commodities) were considered applicable only to RACs treated via a fruit 

3237 and vegetable rinse; whereas, the analogous EPA data requirements apply to both crop 

3238 plants and metabolically-active RACs. The data requirements in EPA’s final rule easily 

3239 subsume the studies suggested by a commenter in Part 2. The commenters feel that 

3240 EPA only has authority to require residue data for RACs of plants treated by a fruit or 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 130 of 233 

3241 vegetable rinse whereas EPA interprets FIFRA and FFDCA, as amended by FQPA, to 

3242 mean that data may be required for any use if necessary to support registration of any 

3243 use under FIFRA (see Units XVI.A. and IV)..). 

3244 As evidenced by the recommendation to divide EPA’s single proposed data 

3245 requirement table into two tables (Parts 1 and 2), the commenters believe the data 

3246 requirements are distinctly different depending on the use pattern of interest. While this 

3247 is sometimes the case, the Agency has found that there is much overlap between which 

3248 studies are necessary to characterize the dietary exposure potentially resulting from a 

3249 given use. This is why the test notes provide the conditions under which each study is 

3250 required, likely to be required, or not required. EPA has historically and currently used a 

3251 single data requirement table for each scientific discipline; doing so permits the 

3252 interrelationships between use pattern, tiering, and data needs to be fully evident. 

3253 The commenters did not account for data needed to estimate dietary exposure 

3254 associated with uses that do not require a FFDCA section 408 tolerance or exemption 

3255 (see Unit XVI.A. and Unit IV)..). The commenters also did not account for data needed 

3256 to estimate dietary exposure from food residues inadvertently resulting from, but not 

3257 limited to, discharges of antimicrobial-treated water from indoor industries, leaching 

3258 from preserved lumber, or treatment of food crops when a public health claim is made 

3259 on the label. 

3260 XVII. Discussion of Key Comments on SAR and QSAR, and the OPPTS (now 

3261 OCSPP) Integrated Testing Vision 

3262 A. Guidance on Policies, Procedures, and Processes

3263 1. Comment. A commenter asked EPA to should provide clear guidance on its 

3264 policies, procedures, and processes on the use of alternative technologies such as SAR 

3265 and QSAR, and the WOE approach. In addition, the commenter stated that EPA should 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 131 of 233 

3266 also provide education and training on these approaches. 

3267 2. EPA’s response. The Agency encourages applicants to create submissions 

3268 that include predictive techniques such as SAR and QSAR to fulfill data requirements. 

3269 As described in the white paper to the proposed rule, entitled, “Use of Structure-Activity 

3270 Relationship (SAR) Information and Quantitative SAR (QSAR) Modeling For Fulfilling 

3271 Data Requirements for Antimicrobial Pesticide Chemicals and Informing EPA’s Risk 

3272 Management Process” (see document 45 in the docket at http://www.regulations.govID 

3273 number EPA-HQ-OPP-2008-0110-0045), an important part of the applicant’s 

3274 submission is the rationale. The rationale, or WOE evaluation, is the part of the 

3275 submission that explains the applicant’s belief as to why and how the predictive data 

3276 would fulfill the data requirement. The WOE approach requires a critical analysis of the 

3277 entire body of available data for consistency and biological plausibility. In support of a 

3278 request that predictive data be considered, the applicant would need to explain why it 

3279 believes the surrogate data or the modeling are appropriate for the intended use and 

3280 are of sufficient completeness and quality, and therefore would fulfill the data 

3281 requirement. The Agency would evaluate each submission with a WOE rationale on a 

3282 case-by-case basis. 

3283 The general types of information that are considered appropriate for a WOE 

3284 approach would include: 

3285 • Sufficiency of data. Studies that completely characterize both the effects and 

3286 exposure of the agent have more credibility and support than studies that contain data 

3287 gaps. 

3288 • Quality of the data. Potentially relevant studies are judged for quality and 

3289 studies of high quality are given more weight than those of lower quality. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 132 of 233 

3290 • Evidence of causality. The degree of correlation between the presence of an 

3291 agent and some adverse effect is an important consideration. 

3292 Regarding SAR/QSAR, the white paper to the proposed rule (p. 30) discusses 

3293 the five criteria set by the OECD for evaluating a model. EPA encourages submitters to 

3294 follow the established criteria set by OECD, and show how the model is validated for 

3295 that particular pesticide chemical structure as a measure of the model’s applicability. 

3296 Different computer software programs are used to estimate/predict different 

3297 hazards (see: http://www.epa.gov/oppt/sf/tools/methods.htm). This means that 

3298 predictive software models for different scientific disciplines are not at the same level of 

3299 development. The Agency has long standing experience in predicting (modeling) 

3300 physical-chemical properties, environmental fate, ecotoxicity, and experience in 

3301 predicting carcinogenesis for certain classes of chemicals. However, the Agency is still 

3302 gaining experience to become familiar with predictive approaches that look at other 

3303 human health endpoints (e.g., reproductive, developmental), which have not been 

3304 widely used at EPA. Given the different stages of predictive software development, 

3305 EPA would expect to undertake a case-by-case evaluation of submitted WOEs. EPA 

3306 encourages the use of integrated approaches that combine the knowledge from existing 

3307 databasesdata bases about the chemical of interest with data from appropriate 

3308 surrogate chemicals. 

3309 EPA agrees that guidance on the policies, procedures, and processes for using 

3310 alternative approaches such as SAR/QSAR is needed. EPA isIn developing such a 

3311 guidance document for pesticides and is seeking, EPA sought to harmonize its 

3312 approach with that of Canada’s Pest Management Regulatory Authority. It is 

3313 anticipated that The guidance document would bewas issued as a North American Free 

3314 Trade Agreement guidance document by the end of 2011.in 2012. This guidance 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 133 of 233 

3315 document will adhereadheres to the five OECD principles that were discussed in the 

3316 white paper. Once finalized, this document will and is now considered to be the 

3317 definitive source of information for applicants seeking to use SAR and QSAR 

3318 approaches for fulfilling data requirements for pesticide registration. For information, 

3319 see http://www.epa.gov/oppfead1/international/naftatwg/guidance/guidance.htm.

3320 B. Integrating SAR/QSAR Within the Data Requirements Rule

3321 1. Comments. One commenter argued that there should be an explicit 

3322 statement that SAR and QSAR can be considered to fulfill data requirements. Another 

3323 commenter had concerns on codifying the use of SAR in 40 CFR part 158, Subpart A 

3324 since that would mean that “SAR/QSAR Techniques would be applicable to 

3325 conventional, biochemical and microbial, and antimicrobials pesticide chemicals.” 

3326 Another commenter requested that SAR/QSAR be fully integrated within the rule. 

3327 2. EPA’s response. EPA has and will continue to consider accepting 

3328 SAR/QSAR to fulfill its data requirements on a case-by-case basis. Acceptance would 

3329 be based on the information provided and most especially on the supporting rationale 

3330 submitted to EPA. The Agency would evaluate the information submitted to determine if 

3331 the applicant has provided information that is of sufficient quality and completeness. 

3332 The Agency notes that validation of QSAR models is necessary before the predictions 

3333 from those models can be fully integrated into the testing requirements. To that end, 

3334 QSAR models must be inclusive of pesticide toxicology data and chemical structures. 

3335 Until these models become customized with pesticide information, full incorporation of 

3336 predictive tools likely will be limited to a case-by-case basis. 

3337 EPA agrees that if use of SAR/QSAR were to be codified in subpart A, that it 

3338 would be applicable to all pesticide chemicals. At this time, EPA is not codifying the use 

3339 of SAR and QSAR in subpart A. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 134 of 233 

3340 XVIII. Discussion of Key Comments on Guidelines 

3341 A. Commenters’ Concerns with Guidelines

3342 1. Comment: Several commenters indicated their belief that the current 

3343 Harmonized Guidelines have significant problems, which include: 

3344  Lack of guidelines could create an unevenness from one company to another 

3345 in how the data requirements are applied. 

3346  Data requirements for which guidelines are not available. 

3347  Older, outdated guidelines that need revision. 

3348  Draft guidelines that need to be finalized. 

3349  Older exposure guidelines that do not include information about the Human 

3350 Studies Review Board. 

3351  Guidelines that were adopted without the opportunity for public comment. 

3352 According to the commenters, lack of current guidelines could create an unevenness 

3353 from one company to another in how the data requirements are applied. The 

3354 commenter argued that the Agency needs to provide current, consistent, and reliable 

3355 guidance and standards for each data requirement. The commenters recommended 

3356 that EPA should finalize all of its guidelines before the final rule is published per the 

3357 recommendation from OMB. 

3358 2. EPA’s response. EPA’s Harmonized Test Guidelines are publicly-available at 

3359 http://www.epa.gov/ocspp/pubs/frs/home/guidelin.htm. The Harmonized Guidelines 

3360 contain recommendations on how to conduct a study that is most likely to provide the 

3361 information needed by EPA for making a registration decision. . 

3362 The Harmonized Guidelines are guidance. The guidelines themselves do not 

3363 impose mandatory requirements. Applicants are not required to submit studies 

3364 developed according to the guidelines to fulfill a data requirement. However, EPA 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 135 of 233 

3365 encourages applicants to use the guidelines. These guidelines were developed to 

3366 provide applicants, who would be conducting the studies, with recognized approaches 

3367 for developing high quality data, guidance on evaluating and reporting data, definition of 

3368 terms, and suggested study protocols. It would not be possible to address every 

3369 conceivable circumstance that could occur when conducting a particular study. Instead 

3370 the guidelines provide a framework that provides recommended approaches for 

3371 conducting studies while offering flexibility and accommodation for individual 

3372 circumstances where appropriate. EPA has reviewed and accepted many studies, on a 

3373 case-by-case basis, that were not conducted in accordance with current guidelines, but 

3374 which provided suitable information for risk assessment purposes. 

3375 Since guidelines cannot account for every conceivable circumstance, EPA, for 

3376 certain studies, proposed a “required” or “highly suggested” protocol submission and 

3377 review step in the test notes to the tables in the proposed rule. Generally, these pertain 

3378 to those studies that are “newer” or have not been routinely conducted. Given that the 

3379 applicant community and contracting laboratories would have less experience in 

3380 conducting these kinds of “newer” studies, protocol submission, review, and meetings 

3381 about proposed protocols are beneficial to both the applicant and EPA, and help assure 

3382 that the study submitted for review should provide the information needed by EPA for its 

3383 registration decision. 

3384 EPA acknowledges that in some instances there are: Data requirements for 

3385 which guidelines are not available; outdated guidelines that need revision; and draft 

3386 guidelines that need to be finalized. Ideally, up-to-date final guidelines would be 

3387 available for every data requirement. Up-to-date guidelines increase the possibility that 

3388 EPA will receive useful data and that applicants can produce such data in the most 

3389 cost-efficient and consistent manner. However, given the rapidly evolving scientific 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 136 of 233 

3390 methods for conducting toxicity, exposure, and ecological studies with pesticides, study 

3391 guidelines often need frequent updating to include the latest techniques and methods. 

3392 Moreover, the need for openness and transparency means that developing a guideline 

3393 or updating an existing one can be a lengthy process. In a recent letter to CropLife 

3394 America (June 26, 2009), (Ref. 1112) the Agency discussed the timeframe for 

3395 developing the Terrestrial Field Dissipation Guideline (835.6100), which spanned 15 

3396 years. During that time period, there were presentations to the SAP, at various 

3397 symposia including ones conducted by the American Chemical Society and the 

3398 American Society of Agronomy, and to a workshop in Washington, DC co-hosted by 

3399 EPA and Canada’s Pest Management Regulatory Agency. 

3400 Thus, the reality is that test guidelines will always be a work in progress. At the 

3401 same time, EPA is implementing a regulatory program under FIFRA and FFDCA section 

3402 408 under which it must make timely decisions on the safety of pesticide products 

3403 based on toxicity and exposure testing. Guidance on optimal testing procedures 

3404 remains an Agency goal but the absence of testing guidelines is not a barrier to the 

3405 imposition of testing requirements necessary to make the required statutory findings. 

3406 In 2008, OMB, during its Executive Order 12866 review of the proposed rule, 

3407 recommended that certain draft guidelines be finalized before publishing the 

3408 Antimicrobial Data Requirements final rule. These guidelines were: 

3409  Applicator product use information (OPPTS 875.1700) 

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

3411  Indoor surface residue dissipation (OPPTS 875.2300). 

3412  Non-dietary ingestion (OPPTS 875.3000). 

3413 In the proposed rule (73 FR 59382, October 8, 2008; 73 FR 59382), EPA 

3414 discussed that the publicly-available versions of these draft guidelines were only 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 137 of 233 

3415 available on the SAP portion of EPA’s website (73 FR 59399 – 59401). 

3416 http://www.epa.gov/scipoly/sap/meetings/1998/march/contents.htm. Since the two 

3417 product use information related guidelines (875.1700 and 875.2700) are expected to 

3418 provide similar guidance for the narrative descriptions that the related data requirements 

3419 call for, EPA intends to finalize these guidelines update them together. 

3420 The indoor surface residue dissipation draft guideline (875.2300) will be updated 

3421 before issued in the near future. final form to account for new advances in how 

3422 exposure is measured and modeled and to provide more information on additional 

3423 methods. EPA intends to revise the draft guideline to expand the methods for 

3424 antimicrobial uses, and has begun to work with EPA’s Office of Research and 

3425 Development (ORD) to develop additional methods (e.g., one current project is to 

3426 develop guidance for testing in small scale air chambers). EPA is also consulting with 

3427 the Consumer Product Safety Commission (CPSC) to review their sampling methods for 

3428 similar products (e.g., chemicals leaching from fabrics). 

3429 Also, as previously discussed, the proposed data requirement referencing the 

3430 non-dietary ingestion guideline was removed from (identified as 875.3000) is not 

3431 included in the final Post-Applicator Exposure Table in § 158.2270. As a result, that 

3432 draft guideline is no longer referenced in Part 158. (See Unit XIII.D)..). 

3433 In addition, as noted in the proposed rule, EPA notes that it has reviewed and 

3434 accepted many studies, on a case-by-case basis, that were not conducted in 

3435 accordance with current final guidelines, but which serve its needs and provide suitable 

3436 information for risk assessment purposes. The guidelines themselves do not impose

3437 mandatory requirements. Instead, they present recognized standards for conducting 

3438 acceptable tests, guidance on evaluating and reporting data, definition of terms, and 

3439 suggested study protocols. The draft guidelines, therefore, serve as a starting point for 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 138 of 233 

3440 developing study protocols. The Agency’s scientists can also provide guidance to

3441 applicants, registrants or task forces on aspects of study design that is often discussed 

3442 at pre-protocol submission meetings. The Agency’s scientists are always willing to work 

3443 with individual applicants or registrants to develop study designs to fulfill data 

3444 requirements.

3445 EPA acknowledges that the guidelines for dermal and inhalation exposure 

3446 studies need revisions to account for new advances in how exposure is measured and 

3447 modeled. To provide needed information to the public and applicants, EPA will change 

3448 the way these guidelines are referenced on the Harmonized Guidelines website by 

3449 adding links to the SAP and Human Studies Review Board (HSRB) meetings at which 

3450 the changes needed to conduct one of these studies were publicly discussed. 

3451 Since the publication of the proposed rule on October 8, 2008, EPA has worked 

3452 to update and finalize a number of guidelines. On April 15, 2009, EPA published In the 

3453 Federal Register of April 15, 2009 (74 FR 17479) (FRL 8352-8) , EPA issued a Notice 

3454 of Availability describing updates to 16 environmental fate guidelines. On

3455 In the Federal Register of January 27, 2010, (75 FR 4380) (FRL 8437-2), EPA 

3456 published four draft product performance guidelines for comment. These four 

3457 guidelines ( (i.e., 810.2000, 810.2100, 810.2200, and 810.2300)). These four guidelines

3458 were developed over an extended period of time with multiple levels of review across 

3459 divisions and program offices in EPA, expert external peer review by the FIFRA 

3460 Scientific Advisory Panel, (SAP), and discussions with and comments from the 

3461 regulated community. After soliciting public comment in 2010, EPA announced the 

3462 availability of the final guidelines in the Federal Register of March 16, 2012 (77 FR 

3463 15750) (FRL 9332–4). Many of the technical changes described in these four draft 

3464 guidelines have been in use by the Agency for several years. Three additional product 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 139 of 233 

3465 performance guidelines (810.2400, 810.2500, and 810.2600) should be published for 

3466 comment in a timeframe similar to that of publication of the final rule for Antimicrobial 

3467 Data Requirements. Similarly, the nontarget organism and plant protection guidelines 

3468 are expected to be finalized by the end of 2011.

3469 Three additional Product Performance Guidelines (i.e., 810.2400, 810.2500, and 

3470 810.2600) published for public comment on September 15, 2011 (76 FR 57031) (FRL 

3471 8879–1), and in the Federal Register of June 27, 2012 (77 FR 38280) (FRL 9349–5), 

3472 EPA announced the availability of the final guidelines. 

3473 Also in the Federal Register of June 27, 2012 (77 FR 38282) (FRL 9333-1), 

3474 EPA announced the availability of 26 Ecological Effects Test Guidelines in Series 850, 

3475 and Groups B, C, D and F. In finalizing the guidelines, EPA changed the numbering 

3476 and/or titles of certain guidelines, and split or merged other guidelines. EPA continues 

3477 to work to revise the remaining Ecological Effects Test Guidelines, Group A, and 

3478 anticipates finalizing many of these guidelines in 2013.

3479 Before finalizing a guideline, EPA provides many opportunities for public 

3480 comment. EPA’s commitment to transparency is not new. Transparency allows all 

3481 stakeholders to know what, how, and why EPA is adopting a guideline. EPA’s 

3482 procedures for developing a guideline is described in a Notice of Availability that 

3483 published on August 28, 1996 (61 FR 44308) (FRL 5390-7): 

3484  Guidelines under development (whether new or being substantially revised) 

3485 are made available for public comment. 

3486  Guidelines under development (whether new or being substantially revised) 

3487 undergo an external peer review process. Most commonly, the peer review process 

3488 would be a review by the FIFRA SAP. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 140 of 233 

3489  Reformatted guidelines (no substantial revisions) are not subject to review 

3490 and comment. 

3491  Public review and comment is also used when EPA guidelines are being 

3492 harmonized with OECD guidelines. 

3493 B. Harmonization of Guidelines with OECD

3494 1. Comment. EPA should harmonize its guidelines with those of OECD. 

3495 2. EPA’s response. EPA agrees with this comment and is continuing to 

3496 harmonize guidelines, to the extent practicable, as they are revised. As noted on its 

3497 website http://www.epa.gov/pesticides/science/guidelines.htm, EPA has several 

3498 harmonization activities underway with the OECD. The Master List of Harmonized Test 

3499 Guidelines includes a reference to an OECD guideline, once harmonized. All 

3500 harmonized OECD test guidelines (http://www.epa.gov/epahome/exitepa.htm) fall under 

3501 the OECD Mutual Acceptance of Data decision, which calls for acceptance for 

3502 regulatory use by all OECD member nations. Additionally, under 40 CFR 158.70(d)(2), 

3503 acceptance of testing conducted in accordance with OECD protocols is described. 

3504 Harmonized test guidelines reduce the burden on chemical producers and 

3505 conserve scientific resources, including the minimal use of laboratory test animals. 

3506 They also form a basis for work sharing and cooperation among all OECD countries. 

3507 U.S. experts are engaged in harmonization activities through OECD to revise 

3508 toxicology and ecotoxicology test guidelines. These revisions will emphasize reduction, 

3509 refinement, or replacement of animal testing, while incorporating the latest advances in 

3510 science. Animal welfare concerns and international regulatory needs are being 

3511 considered in the course of these revisions of the test guidelines. In addition, EPA is 

3512 actively engaged in OECD’s development and harmonization efforts for guidelines to 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 141 of 233 

3513 address environmental fate, endocrine disruptor screening, and efficacy of antimicrobial 

3514 pesticides. 

3515 Tests conducted in accordance with the requirements and recommendations of 

3516 the applicable OECD protocols can be used to develop data necessary to fulfill the data 

3517 requirements. However, some of the OECD recommended test standards, such as test 

3518 duration and selection of test species, are less restrictive than those recommended by 

3519 EPA. When using OECD protocols, applicants should be careful to observe the test 

3520 standards so that the data generated will satisfy the EPA data requirements. 

3521 C. Guidelines Specific to Antimicrobials 

3522 1. Comment. The commenter claimed that guidelines specific to antimicrobials 

3523 are needed. 

3524 2. EPA’s response. EPA agrees that for certain scientific disciplines or certain 

3525 studies that antimicrobial-specific guidance may be needed. The data required to 

3526 demonstrate product performance would be very different for an insect repellent or a 

3527 termiticide versus that needed for sanitizers and disinfectants. Exposure studies could 

3528 be conducted differently for an antimicrobial used in a food-processing plant versus a 

3529 conventional pesticide sprayed on an agricultural field. Exposure studies could also be 

3530 conducted via the same method: A spray can with an insecticide is assessed using the 

3531 same techniques as a spray can with a disinfectant with any differences in the 

3532 assessment being attributed to actual use conditions, such as, indoors versus outdoors 

3533 or surfaces sprayed. For other scientific disciplines such as toxicology or product 

3534 chemistry, generally, with a few exceptions, the guidance would be the same: A 

3535 carcinogenicity, developmental, or reproductive toxicity study would be conducted 

3536 similarly for an antimicrobial or a conventional pesticide. However, as noted in Unit 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 142 of 233 

3537 X.F,., the Ames assay may not be useful for assessment of mutagenic potential of 

3538 antimicrobial pesticides. 

3539 XIX. Discussion of Key Comments on Endangered Species Assessments 

3540 A. Endangered Species Assessment for Antimicrobials 

3541 1. Comment. The commenter argued that EPA needs to recognize the manner 

3542 in which antimicrobials may result in environmental exposure and the regulations under 

3543 statutes other than FIFRA in order to promote an effective and efficient approach to 

3544 regulating antimicrobial pesticides with regard to endangered and threatened species. 

3545 According to the commenter, antimicrobials are not applied directly to the environment, 

3546 but environmental exposures from antimicrobial pesticides result from point-source 

3547 discharges or slow release from pesticide-containing materials. 

3548 2. EPA’s response. EPA agrees that there are differences between 

3549 antimicrobial pesticides and agricultural pesticides. As discussed in the proposed rule 

3550 (October 8, 2008;, 73 FR 59425), for agricultural pesticides, there is generally greater 

3551 specificity relative to where a pesticide may be used compared to antimicrobial 

3552 pesticides. Agricultural pesticides are typically used on crops. As part of its endangered 

3553 and threatened species assessment, EPA extracts information on county-level crop 

3554 occurrence and acreage within counties of particular crops from the most recent U.S. 

3555 Department of Agriculture’sUSDA National Agricultural Statistics Services’ Census of 

3556 Agriculture. Because antimicrobial pesticides are typically not applied directly to the 

3557 environment, it is easier to delineate and overlay agricultural pesticide use with 

3558 endangered or threatened species locations than to delineate and overlay antimicrobial 

3559 pesticides use. Nevertheless, wood preservatives, antifoulant paints and coatings, and 

3560 other antimicrobial uses, including uses in swimming pool water, industrial slimicides 

3561 used in recirculating water cooling towers, and paper mills, have the potential for 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 143 of 233 

3562 environmental exposures. The Agency is working to refine its endangered species 

3563 assessment for antimicrobial pesticides to account for the unique mechanisms involved 

3564 in application and use of antimicrobial pesticides, and the different routes through which 

3565 antimicrobial pesticides enter the environment. 

3566 EPA recognizes that antimicrobials, like any other pesticide product, may be 

3567 subject to other Federal, State and local laws. FIFRA requires that, before a pesticide 

3568 may be lawfully sold or distributed in the United States, the product must be registered 

3569 by EPA, unless the product is exempt from registration requirements. Prior to 

3570 registering a pesticide product, EPA must first ensure that the pesticide, when used 

3571 according to label directions, can be used without posing unreasonable risks to humans 

3572 and the environment. The registration of a pesticide product, whether it is an 

3573 antimicrobial or other type of pesticide product, is considered an “action” subject to the 

3574 Endangered Species Act (ESA). The ESA requires all Federal agencies to ensure that 

3575 any action they permit or authorize will not result in likely jeopardy to the continued 

3576 existence of endangered or threatened species, or destroy or adversely modify habitat 

3577 designated as critical by the U.S. Fish and Wildlife Service (FWS) or National Marine 

3578 Fisheries Service (NMFS). 

3579 In order to ensure EPA’s actions are consistent with the ESA, the Agency must 

3580 assess the potential for both direct and indirect effects to any potentially exposed 

3581 threatened or endangered species and critical habitat, independent of whether exposure 

3582 results from a point-source discharge or the slow release of a pesticide containing 

3583 material. If effects may occur, EPA consults with the FWS or NMFS to determine 

3584 whether there may be jeopardy to the species or destruction or adverse modification to 

3585 habitat designated as critical. 

3586 B. Method for Conducting Endangered Species Assessments 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 144 of 233 

3587 1. Comment. A commenter claimed that EPA/OPP does not have a mature 

3588 program currently in place for antimicrobial environmental risk assessment generally. 

3589 More specifically, the commenter contended that EPA does not have a program in place 

3590 for assessing potential impacts on endangered and threatened species relevant to 

3591 antimicrobials and their uses. The commenter argued that until EPA scientifically 

3592 substantiates data requirements to use in estimating antimicrobial environmental 

3593 exposures and modeling and the potential for risks from such exposures, it will not be 

3594 feasible to make any meaningful determinations on potential impacts to endangered 

3595 species. The commenter concluded that it is thus premature for the EPA to determine 

3596 how it should approach antimicrobials with regard to endangered species. 

3597 2. EPA’s response. EPA disagrees with the commenter. EPA has a robust 

3598 program for completing antimicrobial environmental risk assessments, as outlined in the 

3599 preamble to the proposed rule (73 FR 59405). Environmental fate studies evaluate the 

3600 mobility, distribution and dissipation of a pesticide in various compartments of the 

3601 environment, such as water, soil, air, and sediment. Ecological effects data are used by 

3602 the Agency to determine the toxicological hazards of pesticides to various nontarget 

3603 organisms, such as birds, mammals, fish, bees, terrestrial and aquatic invertebrates, 

3604 and plants. The required environmental fate studies and ecological effects (both plant 

3605 and animal) data provide the foundation for an environmental risk assessment. EPA’s 

3606 environmental risk assessment for antimicrobials combines environmental fate studies 

3607 with ecological effects data to determine the potential of the pesticide to cause harmful 

3608 effects to nontarget organisms and plants. The data requirements that will be codified 

3609 in the final rule will provide sufficient information for EPA to perform an ecological risk 

3610 assessment. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 145 of 233 

3611 EPA/OPP’s process for assessing the potential risks of a pesticide to federally 

3612 listed threatened or endangered species and their designated critical habitat is 

3613 described in the document titled “Overview of the Ecological Risk Assessment Process 

3614 in the Office of Pesticide Programs, U.S. Environmental Protection Agency – 

3615 Endangered and Threatened Species Effects Determinations” released in January 

3616 2004.(Ref. 13). Appendix A to that document – “Overview of OPP’s Screening-Level 

3617 Ecological Risk Assessment Process for Antimicrobial Pesticides” – explains both the 

3618 data needed and the process that would be used by EPA to assess potential risks to 

3619 endangered and threatened species from antimicrobial pesticides. 

3620 EPA’s assessment of potential impacts on endangered and threatened species 

3621 begins with a screening level assessment to determine if there is a potential concern. 

3622 When the screening-level ecological risk assessment raises potential concerns related 

3623 to a listed species, EPA then conducts a species-specific evaluation to refine the 

3624 assessment. The more refined assessment should involve clear delineation of the 

3625 action area associated with the proposed use of the pesticide and best available 

3626 information on the temporal and spatial co-location of the listed species with respect to 

3627 the action area. EPA notes that with the publication of the proposed rule, the discussion 

3628 in Appendix A is out of date. In response to comments received on the proposed 

3629 antimicrobial data requirements, EPA indicated it is no longer relying on its proposed 

3630 approach classifying use patterns as high/low or minimal/significant exposure uses with 

3631 regard to ecological effects testing. However, the Agency’s basic approach to 

3632 endangered species risk assessments, which combine environmental fate studies with 

3633 ecological effects data to determine the potential of the pesticide to cause harmful 

3634 effects to endangered species, has not changed. In addition, the Agency will conduct 

3635 an assessment for antimicrobial pesticides with down -the -drain uses, as described in 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 146 of 233 

3636 response to comment 134.1 in the Response to Comments Document in the docket at 

3637 http://www.regulations.gov.. The codified data requirements and the down -the -drain 

3638 assessment will extend AD’s ability to understand the potential impacts of antimicrobial 

3639 pesticides on endangered species.

3640 EPA cannot wait to comply with the ESA until newer, more advanced, models are 

3641 available or additional data needs are determined: Federal agencies must comply with 

3642 the ESA by performing their assessments and analyses using the best scientific and 

3643 commercial data available. As a part of Registration Review, EPA is conducting 

3644 species-specific environmental risk assessments that will allow EPA to determine 

3645 whether the antimicrobial pesticide product has “no effect” or “may affect” federally3646 listed threatened or endangered species (listed species) or their designated critical 

3647 habitats. When an assessment concludes that a pesticide product’s use “may effect” a 

3648 listed species or its designated critical habitat, the Agency will consult with the FWS 

3649 and/or NMFS, as appropriate. 

3650 XX. Discussion of Key Comments on Endocrine Disruption 

3651 A.1. Comment. The commenters noted that EPA did not include any studies to 

3652 assess endocrine disruption effects.

3653 B.2. EPA’s response. The commenter is correct that EPA did not include within 

3654 the proposed subpart W, studies whose sole purpose is to assess endocrine disruption 

3655 effects in avian and aquatic species. The Agency is also not including such studies in 

3656 this final rule. 

3657 With regards to toxicology data requirements, as required by FIFRA and FFDCA, 

3658 EPA reviews a toxicological databasedata base of numerous studies to assess potential 

3659 adverse outcomes from exposure to chemicals. Collectively, these studies include 

3660 acute, subchronic and chronic toxicity, including assessments of carcinogenicity, 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 147 of 233 

3661 neurotoxicity, developmental, reproductive, and general or systemic toxicity. These 

3662 studies include endpoints which may be susceptible to endocrine influence, including 

3663 effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual 

3664 maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. EPA 

3665 reviews these data and selects the most sensitive endpoints for relevant risk 

3666 assessment scenarios from the existing toxicological databasedata base. 

3667 With regards to ecotoxicity data requirements, as required by FIFRA and FFDCA, 

3668 EPA reviews a nontarget organism databasedata base of numerous studies to assess 

3669 potential adverse outcomes from exposure to chemicals. For ecological hazard 

3670 assessments, EPA evaluates acute tests and chronic studies that assess growth, 

3671 developmental and reproductive effects in different taxonomic groups. EPA reviews 

3672 these data and selects the most sensitive endpoints for relevant risk assessment 

3673 scenarios from the existing nontarget organism database. 

3674 Through a separate effort, the Agency has also developed a screening battery to 

3675 identify chemicals that may have effects on the hormone systems of humans and 

3676 wildlife. As required under FFDCA section 408(p), the Agency developed the Endocrine 

3677 Disruptor Screening Program (EDSP) to determine whether certain substances 

3678 (including pesticide active and other ingredients) may have an effect in humans or 

3679 wildlife similar to an effect produced by a “naturally occurring estrogen, or other such 

3680 endocrine effects as the Administrator may designate.” The EDSP employs a two-tiered 

3681 approach to making the statutorily required determinations. Tier 1 consists of a battery 

3682 of 11 screening assays to identify the potential of a chemical substance to interact with 

3683 the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go 

3684 through Tier 1 screening and are found to have the potential to interact with E, A, or T 

3685 hormonal systems will proceed to the next stage of the EDSP where EPA will determine 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 148 of 233 

3686 which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

3687 testing is designed to identify any adverse endocrine-related effects caused by the 

3688 substance, and establish a dose-response relationship between the dose and the E, A, 

3689 or T effect. 

3690 Between October 2009 and February 2010, EPA issued test orders/data call-ins 

3691 for 58 pesticide active ingredients and nine9 inert ingredients. This list of chemicals 

3692 was selected based on the potential for human exposure through pathways such as 

3693 food and water, residential activity, and certain post-application agricultural scenarios. 

3694 This list should not be construed as a list of known or likely endocrine disruptors. 

3695 Under FFDCA section 408(p) the Agency must screen all pesticide chemicals, 

3696 including antimicrobials. Accordingly, EPA anticipates issuing future EDSP test 

3697 orders/data call-ins for all pesticide active ingredients. 

3698 For further information on the EDSP including the status and test guidelines, 

3699 please visit the website: http://www.epa.gov/endo/. 

3700 XXI. Discussion of Key Comments on Effective Date of Final Antimicrobial Data 

3701 Requirements

3702 A1. Comment. Several commenters have expressed concern over when the final 

3703 rule would take effect. One commenter stated that compliance with the Administrative 

3704 Procedures Act requires EPA to apply any final rulemaking on data requirements for 

3705 antimicrobials only to applications submitted after the effective date; otherwise, EPA 

3706 would be promulgating the final rule retroactively. The commenter also asserted that 

3707 EPA should be consistent in its implementation of effective dates, noting that EPA did 

3708 not impose new data requirements on pending conventional pesticide registrants when 

3709 the conventional pesticide rules were revised. A second commenter suggested that 

3710 registrations pending at the time of the final rule publication be given conditional 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 149 of 233 

3711 registration under section 3(c)(7) of FIFRA or under section 3(c)(5) if the requirements 

3712 of part 161 have been met, and that implementation of the part 158, subpart W data 

3713 requirements occur at the time of periodic registration review. Another commenter 

3714 noted that EPA has provided reasonable notice to registrants and recommends that 

3715 EPA implement the rule as soon as technically feasible. A different commenter 

3716 questioned whether additional Pesticide Registration Improvement Act (PRIA) 

3717 registration fees would be required for pending applications if the registrant did not meet 

3718 new data requirements and withdrew the application, or if the Agency issued a 

3719 determination that it cannot grant the application.

3720 B.2. EPA’s response. EPA will follow an approach similar to that used for 

3721 conventional pesticides following the promulgation of that portion of 40 CFR part 158. 

3722 As previously discussed, the final rule for antimicrobials contains 11 “new” data 

3723 requirements. “New” means that the data requirement has never been required, or has 

3724 rarely been required on a case-by-case basis and has not been routinely considered 

3725 during the Agency’s evaluation of the data needed for the purpose of risk assessment. 

3726 The new data requirements being codified include eight that were proposed and three 

3727 that have been added based on public comments received about the proposed rule. 

3728 EPA recognizes that during early implementation of 40 CFR part 158, subpart W 

3729 not all application packages may have all of the newly-required data. Therefore during 

3730 early implementation of 40 CFR part 158, subpart W, EPA will accept for review and 

3731 evaluation application packages that may not have all of the newly required data in 

3732 appropriate cases supported by adequate justification. This early implementation period 

3733 could extend up to two2 years post-promulgation for situations in which a more time3734 intensive new study is missing but could be less for other situations, such as for less 

3735 time-intensive new studies. The applicant should address the issue of timing (i.e., why 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 150 of 233 

3736 the data are not yet submitted and when the data can be submitted) with respect to any 

3737 missing newly-required data, in their justification. 

3738 EPA is statutorily required to evaluate the proposed pesticide thoroughly to 

3739 ensure that it will not unreasonably harm human health or the environment. For 

3740 pesticides needing FFDCA section 408 tolerances, EPA is statutorily required to make a 

3741 safety finding that the pesticide can be used with "reasonable certainty of no harm." In 

3742 cases where the application may not have all the required data, EPA would evaluate 

3743 whether a registration determination or a safety finding can be made based on the 

3744 available data or on the results of other studies in the pesticide’s databasedata base. If 

3745 there is insufficient information, and if the databasedata base does not provide 

3746 information on the endpoints that would be tested, or data provided by the applicant or 

3747 information in the databasedata base shows evidence of effects, EPA may not be able 

3748 to make a registration decision or safety finding. In such cases, the application may be 

3749 denied or the applicant may choose to withdraw the application pending completion of 

3750 the needed data. In some cases, conditional registrations may be appropriate for 

3751 consideration. Among other things, a determination that the proposed use will not 

3752 significantly increase the risk of unreasonable adverse effects on the environment will 

3753 need to be made. If EPA can make that determination and the other elements for a 

3754 conditional registration are met, then a conditional registration may be appropriate and 

3755 the new data required as a condition of registration. If there is a basis for granting a 

3756 conditional registration, then the timeframe for conditioning the registration would be 

3757 determined based on factors such as the required studies involved and the length of 

3758 time required to conduct those studies. 

3759 Importantly, it should be noted that acceptance of an application for processing 

3760 during early implementation of 40 CFR part 158, subpart W, that does not result in a 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 151 of 233 

3761 conditional registration, does not permanently relieve the applicant from providing the 

3762 newly required data. Based on the particular case involved, the Agency will employ 

3763 appropriate mechanisms, for example, through a DCI or through the registration review 

3764 process, to ensure the generation and submission of any missing newly-required data. 

3765 With respect to pending applications that are withdrawn, additional PRIA 

3766 registration fees will generally only be required if the applicant seeks to pursue the 

3767 action again by submitting a new application (and addressing the deficiencies in the 

3768 original application). In withdrawal situations, the Agency provides a refund for any 

3769 work that the Agency did not perform on the application following a withdrawal. 

3770 Similarly, a determination that the application cannot be granted does not require 

3771 additional PRIA registration fees. In that case, additional fees will only be incurred if the 

3772 application is subsequently withdrawn or denied, and the applicant seeks to pursue the 

3773 action again and submits a new application. 

3774 XXII. Discussion of Key Comments on the Economic Analysis 

3775 A. Comparing Estimates of Cost of the Proposed Rule

3776 1. Comment. A commenter performed an independent economic analysis (EA) 

3777 for the proposed rule. According to the commenter’s analysis, the cost of proposed part 

3778 158, subpart W is greater than that estimated by the EPA. In addition, the unit test 

3779 costs and frequency of tests used in the commenter’s analysis are different than EPA’s. 

3780 2. EPA’s response. EPA reviewed the commenter’s analysis and based on that 

3781 review revised the EA for the final rule. EPA’s evaluation of the commenter’s EA 

3782 indicated there were the following differences between the two EAs: 

3783  The cost estimates used for the studies,

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

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

Page 152 of 233 

3786 The differences between the cost of the proposed rule as estimated by the commenter 

3787 and the cost as assessed by the Agency for new registrations are explained in the 

3788 following subunits. 

3789 i. How data requirement costs are calculated. The annual cost of a data 

3790 requirement is the product of three factors: Unit test cost, probability of the test being 

3791 required, and the number of registrations in the industry per year for the registration 

3792 type and use. That is: “Industry Cost of a data requirement = Unit test cost x test 

3793 probability x number of registrations.” These costs are summed for all data 

3794 requirements, uses, and registration types to get the total annual cost of the data 

3795 requirements for the industry. 

3796 ii. Differences in unit test costs. EPA acknowledges that there are significant 

3797 differences between the Agency’s analysis and the commenter’s analysis regarding the 

3798 unit test costs. According to the commenter’s EA, the costs were provided to them by 

3799 their client’s technical consultants, and are “based on quotes from laboratories, actual 

3800 experience, and professional judgment.” The commenter did not provide sufficient 

3801 information with which to evaluate the commenter’s test cost estimates. Additionally, 

3802 EPA notes that having all test cost estimates ending in zero could be indicative of 

3803 estimation. 

3804 EPA’s unit test costs for each data requirement were obtained by contacting 

3805 established contract research organizations (CROs) to assess what the labs would 

3806 charge to conduct studies according to specific designs provided by EPA, or as 

3807 specified in OPPTS guidelines. (now OCSPP guidelines). Upper and lower cost 

3808 estimates were requested. For each test, the upper cost estimates from each CRO 

3809 were averaged to obtain a high average estimate. A similar calculation was done for 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 153 of 233 

3810 the lower cost estimate. EPA’s estimate is the average of the high and low average 

3811 estimates. 

3812 iii. Test costs and overhead costs. The commenter added 30 percent to their 

3813 test cost estimates to account for the overhead of the registrants managing and 

3814 overseeing the tests they contract to the labs. EPA acknowledges that there are costs 

3815 other than test costs associated with registering and maintaining the registrations of 

3816 pesticide products. Overhead is a not new cost, attributable to the rule, and EPA does 

3817 not believe that overhead costs will change significantly as a result of codifying data 

3818 requirements for antimicrobials. EPA does not include overhead costs in its economic 

3819 analyses of data requirements rules because the Agency accounts for other registration 

3820 costs such as overhead in the Information Collection Request (ICR) for FIFRA Section 3 

3821 Registration under the Paperwork Reduction Act. 

3822 iv. Test probabilities. EPA’s test probabilities (the probabilities of tests being 

3823 required for a registration actions) were based on a sample of 70 actual antimicrobial 

3824 registration actions out of 90 relevant new registration actions during the six6 year 

3825 period beginning 2000 and ending 2005, supplemented with EPA’s scientific judgment. 

3826 The time period (2000-2005) was chosen for EPA’s EA because the analysis in the EA 

3827 was started in 2006. The commenter claims to have based the test probabilities used to 

3828 make their estimates on a sample of 29 registration review cases (not new registrations) 

3829 occurring between 2008 and 2010. 

3830 v. Factors which drive costs for new registrations. To determine the influence of 

3831 the previously-discussed factors on the difference between the commenter’s and EPA’s 

3832 estimates, EPA performed the following analysis on the data requirements costs and 

3833 incremental costs using the same unit test costs and test probabilities used in the 

3834 proposed rule: 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 154 of 233 

3835  To account for the effect of the unit test costs on the data requirements costs 

3836 and incremental costs, EPA substituted the commenter’s unit test costs without 

3837 overhead into EPA’s analysis of the proposed rule using EPA’s test probabilities and 

3838 number of registrations. If there were no changes, this would indicate that the test costs 

3839 were not driving the differences in estimates. 

3840  To account for the effect of test probabilities and number of registrations, EPA 

3841 substituted the commenter’s unit test costs with overhead into EPA’s analysis. In this 

3842 case, the difference between the EPA’s and the commenter’s analysis is contained in 

3843 the test probabilities and number of registrations. If there were no changes, this would 

3844 indicate that the test probabilities and number of registrations were not driving the 

3845 differences between the two analyses. Since the commenter includes overhead in their 

3846 analysis, overhead was included in this comparison to make other things equal so that 

3847 the differences in test probabilities and number of registrations could be isolated. 

3848 vi. Results. The results of the factor analysis are presented in the following 

3849 Table 1. 

3850 Table 1: Comparison of Data Requirement Costs and Factors for New Registrations 

ColumnFactors 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 

3851 

3852 Column A exhibits the data requirements and incremental costs from EPA’s EA 

3853 of the proposed rule. In column B, the data requirements and incremental costs are 

3854 calculated using the commenter’s unit test costs without overhead costs, but EPA’s test 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 155 of 233 

3855 probabilities and number of registrations. Column C is the same as column B, but with 

3856 overhead costs included. Finally, column D exhibits the data requirements and 

3857 incremental costs with overhead as calculated by the commenter. 

3858 The result of the first factor analysis is demonstrated by comparing column A to 

3859 column B. In this case, the difference between the two columns is the unit test costs. 

3860 Inserting the commenter’s unit test costs, without overhead, into the cost estimates with 

3861 EPA’s test probabilities and number of registrations leads to over a 30 percent increase 

3862 in data requirements cost and a nearly 100 percent increase in incremental costs. 

3863 The result of the second factor analysis is demonstrated by comparing columns 

3864 C and D. In this case, the difference between the two columns is in the test probabilities 

3865 and number of registrations. While individual test probabilities may be different in EPA’s 

3866 and the commenter’s analyses, the overall effect of the products of test probabilities and 

3867 number of registrations, when summed with the unit test costs, including overhead, are 

3868 similar in both of these analyses. The resulting differences in data requirements cost 

3869 and incremental costs are less than 2 percent and about 6 percent, respectively. 

3870 Therefore, EPA concludes that any differences in test probabilities and number of 

3871 registrations used as input parameters in the calculations do not have a significant 

3872 effect on the total data requirement cost of new registrations. 

3873 Comparisons across columns A, B, and C also provide information on the portion 

3874 of the cost difference accounted for by overhead costs. Columns A, B, and C compare 

3875 the cost of data requirements using the unit test cost estimates of EPA, and those of the 

3876 commenter with and without overhead. The overhead costs account for more than one3877 half of the difference in the total cost of the data requirements, but less than 40 percent 

3878 of the difference in incremental costs (the incremental cost is the increase costs 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 156 of 233 

3879 between the baseline, (the existing data requirements in part 161, and proposed part 

3880 158, subpart W). 

3881 From this comparison, EPA makes the following conclusions. First, differences 

3882 in test probabilities and number of registrations do not have a significant impact on the 

3883 cost of the rule. Second, even if EPA and the commenter used the same probabilities 

3884 and test costs, inclusion of overhead costs by the commenter would result in a 30 

3885 percent difference in costs. Finally, when the overhead costs are removed from the 

3886 commenter’s analysis, differences in unit test costs between EPA and the commenter 

3887 account for most of the differences in the estimates of the cost of the rule for new 

3888 registrations. 

3889 vi. Revised test costs. In light of the results of the comparison between EPA’s 

3890 and the commenter’s EA, EPA sought to verify its unit test cost estimates. To examine 

3891 the costs submitted by ACC, EPA re-surveyed the cost of conducting studies for 30 data 

3892 requirements: The criteria for selecting which test’s cost to update included how the 

3893 difference in estimates would impact on the cost of the rule, the magnitude of the 

3894 differences in estimates, and the age and source of EPA’s estimates. EPA’s data 

3895 gathering methodology is reproducible, and based on actual data. EPA does not adjust 

3896 the lab’s cost estimates, i.e., the costs are used as obtained from the laboratory. Under 

3897 the Information Quality Act (IQA), EPA must ensure and maximize the quality, 

3898 objectivity, utility, and integrity of the data used in its analyses. 

3899 The re-surveyed test costs are used in the EA (economic analysis) for the final 

3900 rule. EPA is using its cost estimates because it has revised its most relevant and oldest 

3901 unit test cost estimates. In addition, the commenter did not provide a basis or sufficient 

3902 explanation that would meet the standards of the IQA to justify EPA’s accepting the 

3903 commenter’s costs. For additional information see response to comment 40.1 in the 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 157 of 233 

3904 Response to Comments Document and the final economic analysis, both in the docket

3905 at http://www.regulations.gov. 

3906 B. Impact on Small Businesses 

3907 1. Comment. A commenter claimed that EPA underestimated costs, is not fully 

3908 complying with the Regulatory Flexibility Act (RFA) and the Small Business Regulatory 

3909 Enforcement Fairness Act (SBREFA), and must prepare an Initial Regulatory Flexibility 

3910 Assessment (IRFA). In addition, the commenter argued that small businesses will be 

3911 adversely affected, that there will be an "increased disparity between registrants and a 

3912 more uneven playing field," and finally, that a SBREFA analysis should have been 

3913 conducted. 

3914 2. EPA’s response. EPA acknowledges that the cost of the data requirements 

3915 would likely be a larger percentage of a small business’s revenues, but did not find that 

3916 the rule would have a significant adverse economic impact on a substantial number of 

3917 small firms. 

3918 A regulatory flexibility analysis examines the type and number of small entities 

3919 potentially subject to the rule, recordkeeping and compliance requirements, and 

3920 significant regulatory alternatives, among other things. RFA, as amended by SBREFA, 

3921 requires EPA to consider the economic impact of proposed rules on small entities. RFA 

3922 requires EPA to prepare an IRFA for each proposed rule, when the rule will have a 

3923 significant economic impact on a substantial number of small entities. 

3924 To comply with RFA, EPA did a retrospective analysis of what the additional 

3925 costs would have been on actual new registrations if the proposed rule had been in 

3926 effect during 2000-2005. This analysis did not indicate a significant impact on a 

3927 substantial number of small entities; instead, the analysis indicated that 5 percent of 

3928 small firms (25 out of 500) are likely to experience some impact and only 2.8 percent of 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 158 of 233 

3929 small firms (14 out of 500) are likely to experience an economic impact of 3 percent or 

3930 more of gross sales. Based on this analysis, EPA certified that the proposed rule would 

3931 not have a significant adverse economic impact on a substantial number of small firms. 

3932 As a result, EPA did not have to conduct an IRFA nor convene a SBREFA Panel for the 

3933 proposed part 158, subpart W rule. 

3934 In the EA for the final rule, EPA re-estimated the SBREFA analysis with revised 

3935 unit test costs and changes in data requirements. 

3936  About 23 small firms (almost 5%) are likely to experience an economic impact 

3937 of 3% or more of gross sales, and 

3938  About 26 small firms, (over 5%) are likely to experience an economic impact of 

3939 1% or more of gross sales.

3940 Hence, had these results been estimated at the proposal stage, EPA would still 

3941 have concluded that there would not be a significant impact on a substantial number of 

3942 small entities. 

3943 C. Cost of New Data Requirements on Registration Review

3944 1. Comment. A commenter stated that EPA has not accurately stated the 

3945 potential costs and benefits, as required by Executive Order (EO) 12866. In particular, 

3946 EPA has not included the impact of incremental costs of new data requirements on 

3947 registration review, or the cost of consultations. The commenter also claims that under 

3948 the PRA, EPA should include the paperwork burden costs of registration review for 

3949 existing registrants. 

3950 2. EPA’s response. EO 12866 requires the Agency to submit to OMB for review 

3951 significant regulatory actions. EPA complied with EO 12866 during 2008 by submitting 

3952 drafts of both the economic analysis and the proposed rule to OMB. The changes that 

3953 were made to the proposed rule as the result of OMB’s review were included in the 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 159 of 233 

3954 docket for the proposed rule at http://www.regulations.gov.. The Agency notes that one 

3955 purpose of soliciting comments on the economic analysis at the proposal stage is to get 

3956 input on where the Agency might improve the economic analysis. 

3957 The commenter is not correct in asserting that EPA did not include the impact of 

3958 incremental costs. The Agency has captured the anticipated costs necessary for 

3959 complying with the regulations. See the final Economic Analysis (Ref. 131) in the 

3960 docket at for a more detailed discussion, particularly sections 5.3 and 5.5. 

3961 The commenter is correct in that the costs of fulfilling the 11 “new” data 

3962 requirements during registration review were not considered in the Agency’s economic 

3963 analysis of the proposed part 158, subpart W data requirements. EPA agrees with the 

3964 commenter that registrants of existing antimicrobial products will incur costs during 

3965 registration review. In fact, EPA relied on the 2005 EA conducted for the Registration 

3966 Review Rule. When registration review was proposed, EPA prepared an economic 

3967 analysis of that program, which estimated the cost of data requirements and paperwork 

3968 burden according to what would likely be required in registration review for existing 

3969 registrants. The 2005 registration review EA estimate of data requirement costs for 

3970 existing antimicrobial pesticides was based on what would likely be required for a 

3971 sample of antimicrobial active ingredients. This would have included all tests that would 

3972 have been required at that time, i.e., those in current practice whether or not in part 158. 

3973 However, the proposed part 158, subpart W included “new” tests, which were not 

3974 anticipated when the economic analysis of the registration review process was 

3975 completed. In a final economic analysis for part 158, subpart W, EPA addresses the 

3976 additional registration review costs for these 11 “new” studies, as well as other changes 

3977 from the proposed rule to the final rule, including changes made as a result of the 

3978 comments received. The incremental impact for Registration Review is $ 6.8 Mmillion. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 160 of 233 

3979 The commenter is also correct that EPA did not include the cost of consultation in 

3980 its economic analysis. Consultations are longstanding, commonly used, and valuable 

3981 processes in EPA’s Pesticide Program and are beneficial to both EPA and the 

3982 applicants. However, consultations are not mandatory, and based on comments 

3983 received EPA has removed all references to consultations from the final data 

3984 requirements tables. See Unit V.C. for additional information on the use and purpose of 

3985 consultations. 

3986 XXIII. References 

3987 As indicated under ADDRESSES, a docket has been established for this 

3988 rulemaking under docket ID number EPA-HQ-OPP–2008–0110. The following is a 

3989 listing of the documents that are specifically referenced in this proposed rule. The 

3990 docket includes these documents and other information considered by EPA in 

3991 developing this rule, including documents that are referenced within the documents that 

3992 are included in the docket, even if the referenced document is not physically located in 

3993 the docket. For assistance in locating documents, please consult the technical contact 

3994 listed under FOR FURTHER INFORMATION CONTACT. 

3995 Ref. 1: Rule Text of. USEPA, Final Economic Analysis of Changes in Data 

3996 Requirements for Antimicrobial Pesticides, (INSERT: date of FINAL EA after OMB 

3997 review).

3998 2. USEPA, “Data Requirements for Pesticide Registration; Final Rule;” ” (49 FR 

3999 42856, October 26, 2007)(FRL 8106-5). 

4000 Ref. 2:3. ACC Biocides Panel; “Regulation of Antimicrobials that are Indirect or 

4001 Secondary Direct Food Additives;” (February 2, 2006). 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 161 of 233 

4002 Ref. 3: ACC4. CMA Biocides Panel; “Comments on EPA’s September 17, 1999 

4003 Proposed Rule on Registration Requirements for Antimicrobial Pesticide Products and 

4004 Other Pesticide Regulatory Changes for Codification; (January 18, 2000). 

4005 Ref. 4:5. ACC Biocides Panel; Memorandum to Frank Sanders, “EPA’s Current 

4006 Interpretation of the Antimicrobial Reform Technical Corrections Act and Section 2(bb) 

4007 of FIFRA is Inconsistent with the Statutes;” (AugustNovember 3, 2000). 

4008 Ref. 5:6. ACC Biocides Panel; “EPA/FDA Jurisdiction for Food Contact 

4009 Antimicrobials;” (July 17, 2003). 

4010 Ref. 6:7. Grizzle, Charles L.; representative of Albright & Wilson Americas, Inc., 

4011 letter to Lynn R. Goldman; (September 11, 1997). 

4012 Ref. 7:8. ChemReg International, L.L.C.; Tiered Testing for Risk Assessment of 

4013 Antimicrobial Pesticides; (September 12, 2002). 

4014 Ref. 8:9. Goldberg, Seth; “Section 2(bb) of FIFRA; Dual Jurisdiction Over Food 

4015 Contact Antimicrobials; (April 27, 2001). 

4016 Ref. 9:10. ACC Biocides Panel; “Comments on The Preliminary Risk Assessment 

4017 for 1,4-Bis(bromoacetoxy)-2-butene (BBAB);” (August 6, 2001). 

4018 Ref. 10:11. ACC Biocides; Hasmukh C. Shah letter to Frank T. Sanders; 

4019 (August 3, 2000). 

4020 Ref. 11:12. Edwards, Deborah; OPP Response to CropLife letter of May 29, 

4021 2009; (June 26, 2009). 

4022 Ref. 12:13. Overview of the Ecological Risk Assessment Process in the Office of 

4023 Pesticide Programs, U.S. Environmental Protection Agency – Endangered and 

4024 Threatened Species Effects Determinations (January 2004) (see 

4025 www.epa.gov/espp/consultation/ecorisk-overview.pdf).

4026 14. Portier; SAP Waiver; (April 4, 2011). 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 162 of 233 

4027 Ref. 13: USEPA; Final Economic Analysis of Changes in Data Requirements for 

4028 Antimicrobial Pesticides (update date after OMB review).

4029 XXIV. FIFRA Review Requirements 

4030 In accordance with FIFRA section 25(a), a draft of this final rule was submitted to 

4031 the FIFRA Scientific Advisory Panel (SAP).SAP. EPA requested the FIFRA SAP to 

4032 waive its review of the final rule based on fact that the SAP, in 2008, had waived review 

4033 of the proposed rule: The final rule does not contain any new scientific issues 

4034 warranting additional review by the SAP. The SAP waived its review on April 4, 2011, 

4035 stating that “[t]he final rule does not contain scientific issues that the Panel has not 

4036 previously considered” (Ref. 1214). 

4037 In accordance with FIFRA section 25(a), EPA has submitted a draft of the final 

4038 rule to the appropriate Congressional Committees and the Secretary of the Department 

4039 of Agriculture. There were no comments in response to these submissions. 

4040 In accordance with FIFRA section 21(b), EPA submitted a draft of the final rule to 

4041 the Secretary of Health and Human Services (HHS). Their comments on the draft of the 

4042 final rule included requests to expand further the discussion on “the differentiation of 

4043 authorities of the Food [and] Drug Administration (FDA) and EPA on regulation of 

4044 antimicrobial pesticides when present in food,” and also, various edits were requested 

4045 by FDA’s Office of General Counsel (OGC). In response, EPA has expanded the 

4046 differentiation discussion and made various edits. Both EPA’s OGC and FDA’s OGC 

4047 vetted the changes.), and that the agency’s comments were reviewed and addressed in 

4048 this final rule. 

4049 HHS also requested that EPA further clarify the “guidance for product registrants 

4050 in using emerging alternate test methods in evaluation of toxicity.” EPA agrees that 

4051 because the science is changing rapidly, continuous communication with stakeholders 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 163 of 233 

4052 will be important to their understanding of the availability of alternate test methods that 

4053 OPP would consider. OPP established the PPDC workgroup on 21st Century 

4054 Toxicology to support this communication. Information on OPP's transition to alternate 

4055 methods is available on EPA's website on OPP’s 21st Century toxicology vision and 

4056 strategy webpage, which contains a tools matrix that describes plans to incorporate new 

4057 scientific tools.

4058 FDA also noted that “the data requirements do not appear to consider impacts of 

4059 the proposed pesticide use on antimicrobial resistance development.” As discussed in 

4060 the proposed rule, EPA is a participant on the Interagency Task force on Antimicrobial 

4061 Resistance. While the focus of this group is on the use of antibiotics, the Antimicrobials 

4062 Division (AD) has participated in the taskforce efforts by providing review and comment 

4063 on documents related to antimicrobial resistance, specifically, the reports of the Codex 

4064 Ad Hoc Intergovernmental Task Force on Antimicrobial Resistance, issued through the 

4065 Codex Alimentarius Commission. AD also conducted a literature search into the use of 

4066 antimicrobial pesticides and the development of resistant bacteria. While this literature 

4067 search is several years old, AD does not believe that there have been substantial 

4068 changes since the search was conducted.

4069 The results of the literature search did not support a finding that the use of 

4070 antimicrobial pesticides leads to development of resistant bacteria. EPA does consider 

4071 the impacts of a pesticide's use on the development of antimicrobial resistance. 

4072 However, EPA is unaware of a data requirement approach that would fit this 

4073 circumstance. Antimicrobial resistance develops in the environment during use, or as a 

4074 result of the use when the micro-organisms that are still present "swap their genetic 

4075 material." The efficacy studies required as part of the application submission provide 

4076 information on the product's ability to kill or deactivate the micro-organism when used 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 164 of 233 

4077 according to the directions on the product. Historically, the concentration of the 

4078 antimicrobial in the product is set well-over the minimum inhibitory concentration, to 

4079 assure that the micro-organism is killed or deactivated. If information indicated that an 

4080 antimicrobial product was not performing effectively, then it is likely that the 

4081 manufacturer would request an amendment to their registration to increase the 

4082 concentration of the antimicrobial in the product. EPA has been unable to determine to 

4083 what extent there is a problem of antimicrobial resistance or what data submitted as part 

4084 of a registration package could predict the environmental conditions for developing 

4085 resistance in the future. EPA therefore watches, monitors, and mitigates, as needed.

4086 XXV. Statutory and Executive Order Reviews

4087 A. Executive Order 12866: Regulatory Planning and Review and Executive Order 

4088 13563: Improving Regulation and Regulatory Review

4089 Under Executive Order 12866, entitled Regulatory Planning and Review (58 FR 

4090 51735; October 4, 1993), this action is a “significant regulatory action” because this 

4091 action might raise novel legal or policy issues arising out of legal mandates, the 

4092 President’s priorities, or the principles set forth in the Executive Order. Accordingly, 

4093 EPA submitted this action to the Office of Management and Budget (OMB) for review 

4094 under Executive Orders 12866 and 13563, entitled Improving Regulation and 

4095 Regulatory Review (76 FR 3821; January 21, 2011). Any changes made in response to 

4096 OMB recommendations have been documented in the docket for this action. 

4097 EPA has prepared an EA of the potential costs associated with this action, 

4098 entitled “Final Economic Analysis of Changes in Data Requirements for Antimicrobial 

4099 Pesticides” (Ref. 131), a copy of which is in the docket at http://www.regulations.gov. 

4100 This final EA evaluates the potential benefits and costs expected as a result of 

4101 registrations and registration reviews. The EA is briefly summarized here. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 165 of 233 

4102 In its analysis, the Agency considered the potential, additional costs for the 

4103 registration of new antimicrobial pesticides or new uses of currently registered 

4104 antimicrobial pesticides, as well as the potential, additional costs incurred during the 

4105 registration review of existing antimicrobial pesticides. 

4106 Based on comments received during the public comment period, the following 

4107 changes were made to the rulemaking, and are therefore reflected in the final EA: 

4108  One proposed data requirement will not be codified: Non-dietary ingestion 

4109 exposure. The test cost is $75,000. In the proposed rule, EPA expected to receive the 

4110 test 0.8 times per year, representing an annual industry savings of $63, 125.

4111  EPA revised certain of the data requirements from “NR” or “CR” to “R,” or 

4112 vice-versa. 

4113  Based on comments received, three new data requirements were added: 

4114 Simulation test to assess the biodegradability of chemicals discharged in wastewater, 

4115 simulation test – aerobic sewage treatment: activated sludge units, and nature of the 

4116 residue on surfaces. The rationale for these three new studies is described in Unit 

4117 III.DB. 

4118 The estimated costs for both registration review and for a registration action for 

4119 the three newly-required data requirements are: 

4120 1. Simulation tests to assess the biodegradability of chemicals in discharged 

4121 wastewater and simulation test – aerobic sewage treatment: activated sludge units. 

4122 Both of these studies are used as part of the down -the -drain analysis for 

4123 antimicrobials. The studies are conditionally required for all use patterns, except for the 

4124 aquatic areas use pattern, for which the study is not required. EPA does not have an 

4125 estimate for the cost of either of these studies; instead, for the EA, EPA used the value 

4126 $33,000, which is the cost of the porous pot test. The Agency expects, however, that 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 166 of 233 

4127 the cost of the simulation tests will be less than this amount. For registration review, 

4128 EPA expects to receive the porous pot test or one of the simulation tests up to 8.5 times 

4129 per year, for an annual industry cost of $280,500. For new registrations, EPA expects 

4130 to receive either of the studies up to 7.5 times per year, for an annual industry cost of 

4131 $247,500. The total annual cost is $528,000. 

4132 2. Nature of residue on surfaces. This test is part of the residue chemistry data 

4133 requirements, and is conditionally required for all use pattern categories. The test cost 

4134 is $95,000. For registration review, EPA expects to receive this test 1.3 times per year, 

4135 for an annual industry cost of $118,750. For new registrations, EPA expects to receive 

4136 this test up to 0.5 times per year, for an annual industry cost of $44,333. The total 

4137 annual cost is $163,083.

4138 Many test notes for data requirements were revised based on comments 

4139 received. Data requirements for certain use patterns were changed from “NR” or “CR” 

4140 to “R,” while others were changed from “R” to “CR.” Because the cost of the rule 

4141 depends, in part, on the probabilities of the tests being required, these revisions have 

4142 resulted in a modification of the cost of the rule. Instead of estimating the cost of each 

4143 change individually, the Agency re-estimated the potential cost of the regulation as a 

4144 whole, taking into account the changes discussed abovepreviously. 

4145 Based on comments received, EPA has updated the unit test costs for 30 

4146 selected tests. The criteria for selecting which test’s cost to update included: 

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

4148  The magnitude of the difference between EPA’s cost estimate and the 

4149 commenters’ cost estimate, and 

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

Page 167 of 233 

4151 EPA estimated the annual cost of registering a new antimicrobial pesticide or 

4152 new use of currently-registered antimicrobial pesticides, taking into account both the 

4153 changes in data requirements and in unit test costs. Both the total annual industry costs 

4154 and the newly-imposed costs were estimated. The updated test costs plus exposure 

4155 and other test costs revisions since the proposed rule increased the cost of the rule by 

4156 about 23 percent compared to the proposed rule. The estimated total annual industry 

4157 costs of the final rule is expected to be about $19.3 million, which is approximately 29 

4158 percent higher than the cost of the proposed rule. The difference between the baseline 

4159 costs (the existing data requirements that were codified in 1984) and the cost of the 

4160 Agency’s current practices is about $1 million annually. The difference between the 

4161 baseline costs and the final rule costs, i.e., the incremental costs is approximately $8.2 

4162 million annually. Under the final rule, the average cost per registration action of a new 

4163 antimicrobial active ingredient is approximately $1 million to $5 million. 

4164 For existing chemicals, data requirements in part 158, subpart W are relevant to 

4165 the registration review program which began to replace the reregistration program in 

4166 2006 as a means of systematically reevaluating existing registrations against the 

4167 standards of FIFRA. 

4168 EPA has evaluated the impact of the data requirements being codified todayin 

4169 this final rule on registrants of existing chemicals undergoing registration review whose 

4170 active ingredient databasesdata bases do not contain all of the new data requirements. 

4171 The average additional cost of registration review as a result of the new data 

4172 requirements is estimated to be about $588,000 for wood preservatives, $284,000 for 

4173 food and indirect food uses, and $260,000 for all other uses. For registration review, 

4174 the total annual cost is $6.8 million. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 168 of 233 

4175 As required, EPA conducted an analysis of the impact of this final rule on small 

4176 businesses, as discussed in the Unit XXV.C. 

4177 B. Paperwork BurdensReduction Act (PRA) 

4178 The information collection requirements contained in this rule have been 

4179 submitted for approval to OMB under the Paperwork Reduction Act (PRA),, 44 U.S.C. 

4180 3501 et seq. At the time of the proposed rule, EPA prepared a supporting statement for 

4181 amending an ICR), entitled “Data Requirements for Antimicrobial Pesticides (Proposed 

4182 Rule)” and identified by EPA ICR No. 2318.01, a copy of which is in the docket at 

4183 http://www.regulations.gov..

4184 Under PRA, “burden” means the total time, effort, or financial resources 

4185 expended by persons to generate, maintain, retain, or disclose or provide information to 

4186 or for a Federal agency. 

4187 The information collection activities related to the submission of data to EPA in 

4188 order to register, amend or retain a new or existing pesticide product or obtain a 

4189 tolerance for that product are already approved by OMB under PRA. As such, the 

4190 supporting statement only addresses the proposed changes to the data requirements 

4191 that impact the information collection activities related to antimicrobial pesticides. The 

4192 procedures for submitting data to EPA under FIFRA and FFDCA are not changed in this 

4193 proposal, and are already approved by OMB in the following ICRs: 

4194  Tolerance ICR. Data Submission Activities Associated with Tolerance 

4195 Actions (currently approved under OMB Control No. 2070-0024 (EPA ICR No. 0597)); 

4196  Registration ICR. Data Submission Activities Associated with the Application 

4197 for a New or Amended Registration of a Pesticide (currently approved under OMB 

4198 Control No. 2070-0060 (EPA ICR No. 0277)); and 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 169 of 233 

4199  Reregistration, Special and Registration Review ICR. Data Submission 

4200 Activities Associated with the Generation of Data for Special Review or Registration 

4201 Review (currently approved under OMB Control No. 2070-0174 (EPA ICR No. 2288)). 

4202 These three program activities are an integral part of the Agency’s pesticide 

4203 program, including antimicrobial pesticides, and the corresponding ICRs are regularly 

4204 renewed every 3 years as required by PRA. The total estimated average annual public 

4205 reporting burden currently approved by OMB for these various activities range from 8 

4206 hours to approximately 3,000 hours per respondent, depending on the activity and other 

4207 factors surrounding the particular pesticide product. 

4208 In the supporting statement the Agency estimates that the typical, current annual 

4209 paperwork burden for registrants per antimicrobial pesticide registration is 194 burden 

4210 hours and $12,631. The total annual registrant paperwork burden and costs for data 

4211 submission activities for antimicrobial pesticides applicants and registrants will be 

4212 updated accordingly in the ICRs specified abovein this discussion during the next, 

4213 appropriate ICR renewal cycle. 

4214 An agency may not conduct or sponsor, and a person is not required to respond 

4215 to an information collection request unless it displays a currently valid OMB control 

4216 number, or is otherwise required to submit the specific information by a statute. The 

4217 OMB control numbers for EPA’s regulations codified in Title 40 of the Code of Federal 

4218 Regulations, after appearing in the preamble of the final rule, are further displayed 

4219 either by publication in the Federal Register or by other appropriate means, such as on 

4220 the related collection instrument or form, if applicable. The display of OMB control 

4221 numbers for certain EPA regulations is consolidated in a list at 40 CFR 9.1. 

4222 C. Small Entity Impacts

4223 The Regulatory Flexibility Act (RFA)
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 170 of 233 

4224 The RFA, 5 U.S.C. 601 et seq., generally requires an Agency to prepare a 

4225 regulatory flexibility analysis of any rule subject to notice and comment rulemaking 

4226 requirements under the Administrative Procedure Act or any other statute unless the 

4227 agency certifies that the rule will not have a significant economic impact on a substantial 

4228 number of small entities. Small entities include small businesses, small organizations 

4229 and small governmental jurisdictions.

4230 For purposes of assessing the impacts of today'sthis final rule on small entities, 

4231 small entity is defined as: 

4232 (1). A small business as defined by the Small Business Administration’s (SBA) 

4233 regulations at 13 CFR 121.201, which is based on either the maximum number of 

4234 employees or on the sales for small businesses in each industry sector, as defined by a 

4235 6-digit NAICS code, and for this rule is a producer of pesticide products (NAICS 32532), 

4236 antifoulants (NAICS 32551), antimicrobial pesticides (NAICS 32561) or wood 

4237 preservatives (NAICS 32519), importers of such products, or any person or company 

4238 who seeks to register an antimicrobial, antifoulant coating, ballast water treatment, or 

4239 wood preservative pesticide or to obtain a tolerance for such a pesticide; 

4240 (2). A small governmental jurisdiction that is a government of a city, county, town, 

4241 school district or special district with a population of less than 50,000; or 

4242 (3). A small organization that is any not-for-profit enterprise which is 

4243 independently owned and operated and is not dominant in its field. 

4244 After considering the economic impacts of this final rule on small entities, I certify 

4245 that this action will not have a significant adverse economic impact on a substantial 

4246 number of small entities. The factual basis for the Agency’s determination is presented 

4247 in the small entity impact analysis prepared as part of the Economic Analysis for this 

4248 final rule (Ref. 131), which is available in the docket at http://www.regulations.gov.. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 171 of 233 

4249 EPA has determined that this rulemaking does not impact any small governmental 

4250 jurisdictions or any small non-for-profit enterprise because these entities are rarely 

4251 pesticide applicants or registrants. As such, EPA has assessed the impacts on small 

4252 businesses. Some of the small entities directly regulated by this rulemaking are in the 

4253 pesticide and other agricultural chemical manufacturing industry sector (NAICS code 

4254 325320). Firms in this sector are considered small under the SBA definition if they 

4255 employ 500 or fewer people. The economic analysis for the final rule specifies the 

4256 NAICS code used for each of the firms analyzed. 

4257 EPA estimates that 750 unique parent companies constitute the total universe of 

4258 pesticide antimicrobial registrants. Of these, based on the SBA definition of a small 

4259 business and the available sales data for these firms, EPA estimates that 500, or 

4260 approximately 67 percent, qualify as a small business. When considering both 

4261 registration review and new registrations, on average each year about 30 small 

4262 businesses would have incurred additional costs under this rule. EPA estimates that: 

4263  About 23 small firms (almost 5 percent of the 500 small antimicrobial firms) 

4264 subject to this regulation are likely to experience an economic impact of 3 percent or 

4265 more of gross sales, 

4266  About 3 small firms (0.6 percent of the 500 small antimicrobial firms) subject 

4267 to this regulation are likely to experience an economic impact of greater than 1 percent 

4268 but less than 3 percent of sales revenues, and 

4269  About 3 small firms (0.6 percent of the 500 small antimicrobial firms) subject 

4270 to this regulation are likely to experience an economic impact of greater than 0 percent, 

4271 but less than 1 percent of sales revenues. 

4272 In addition, there are also opportunities for small entities to lower their potential 

4273 costs. The proposed data requirements in many instances are tiered, with higher-tiered 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 172 of 233 

4274 testing triggered on the results of lower-tiered testing. EPA encourages registrants to 

4275 consult with the Agency to ensure that only the required data is submitted. If available, 

4276 open literature or the same tests on similar products, or alternative means to meet data 

4277 requirements, such as QSAR, can be submitted for Agency consideration. Some firms 

4278 may have surrogate data or they may share the cost of generating data. These may 

4279 present opportunities for cost savings by small entities, and all other applicants as well, 

4280 while allowing the Agency to fulfill its role of making pesticide regulatory decisions that 

4281 protect the general population, sensitive sub-populations, and the environment. 

4282 This rule was proposed on October 8, 2008. Small entities were able to provide 

4283 comments during the 90 day public comment period, which was extended an additional 

4284 90 days at the request of stakeholders. On November 6, 2008, EPA convened a public 

4285 workshop to explain the provisions of the proposed rule, arranging for the workshop to 

4286 be webcast for those who could not attend the public workshop in person. 

4287 D. Unfunded Mandates 

4288 Under Title II of the Unfunded Mandates Reform Act of 1995 (UMRA) (2 U.S.C. 

4289 1531-1538),

4290 Title II of UMRA, 2 U.S.C. 1531-1538, establishes requirements for Federal 

4291 agencies to assess the effects of their regulatory actions on State, local, and tribal 

4292 governments and the private sector. EPA has determined that this final rule does not 

4293 contain a Federal mandate that may result in expenditures of $100 million or more for 

4294 State, local, and tribal governments, in the aggregate, or the private sector in any one 

4295 year. As described in Unit XXV.A,., the incremental costs for this final rule is estimated 

4296 at approximately $8.3 million (for registration actions) and $6.8 million (for registration 

4297 review) per year for the private sector, which is below the $100 million threshold. Since 

4298 State, local, and tribal governments are rarely pesticide applicants, this rule is not 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 173 of 233 

4299 expected to significantly or uniquely affect small governments. Accordingly, this rule is 

4300 not subject to the requirements of sections 202 and 205 of UMRA. 

4301 This rule is also not subject to the requirements of section 203 of UMRA because 

4302 it contains no regulatory requirements that might significantly or uniquely affect small 

4303 governments. As stated abovepreviously, State, local, and tribal governments are rarely 

4304 pesticide applicants. 

4305 E. E. Executive Order 13132: Federalism 

4306 This action does not have federalism implications, because it will not have 

4307 substantial direct effects on the States, on the relationship between the national 

4308 government and the States, or on the distribution of power and responsibilities among 

4309 the various levels of government, as specified in Executive Order 13132 (64 FR 43255; 

4310 August 10, 1999). Since States or local governments are rarely pesticide applicants or 

4311 registrants, this final rule would seldom affect a State or local government. Thus, 

4312 Executive Order 13132 does not apply to this rule. 

4313 In the spirit of Executive Order 13132 and consistent with EPA policy to promote 

4314 communication between EPA, and State and local governments, EPA specifically 

4315 solicited comment on the proposed rule from State and local officials. EPA did receive 

4316 comments on substantive parts from local sanitation districts and associations 

4317 representing their interests. Their comments are addressed in the Response to 

4318 Comments Document in the docket at http://www.regulations.gov, and, as appropriate, 

4319 revisions were made for the final rule. 

4320 F. F. Executive Order 13175: Consultation and Coordination with Indian Tribal 

4321 Government Implications

4322 This action does not have tribal implications, as specified in Executive Order 

4323 13175 (65 FR 67249, November 9, 2000). At present, no tribal government holds, or 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 174 of 233 

4324 has applied for, a pesticide registration. Thus, Executive Order 13175 does not apply to 

4325 this action. In the spirit of the Order, and consistent with EPA policy to promote 

4326 communications between the Agency and Indian tribes, EPA specifically solicited 

4327 comment on the proposed rule from tribal officials. No comments were received. 

4328 G. Protection of Children’s Health

4329 This final rule is not subject to Executive Order 13045, entitled: Protection of Children 

4330 from Environmental Health Risks and Safety Risks (62 FR 19885, April 23, 1997) 

4331 because. 

4332 EPA interprets Executive Order 13045 (62 FR 19885, April 23, 1997), as 

4333 applying only to those regulatory actions that concern health or safety risks, such that 

4334 the analysis required under section 5-501 of the Executive Order has the potential to 

4335 influence the regulation. This final rule is not subject to Executive Order 13045because

4336 it is not economically significant as defined by Executive Order 12866, and because the 

4337 Agency does not have reason to believe the environmental health or safety risks 

4338 addressed by this action present a disproportionate risk to children. This rule does not 

4339 propose an environmental standard that is intended to have a negatively 

4340 disproportionate effect on children. To the contrary, this rule is intended to provide 

4341 added protection to children from antimicrobial pesticide risk. EPA will use the data and 

4342 information obtained by this action to carry out its mandate under FFDCA to give special 

4343 attention to the risks of pesticides to sensitive groups in early lifestages, especially 

4344 infants and children. 

4345 H. Executive Order 13211: Actions Concerning Regulations that Significantly Affect 

4346 Energy Supply, Distribution, or Use 

4347 This final rule is not subject to Executive Order 13211, entitled Actions 

4348 Concerning Regulations that Significantly Affect Energy Supply, Distribution, or Use (6
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 175 of 233 

4349 (66 FR 28355, May 22, 2001) because it is not an economically significant regulatory 

4350 action under Executive Order 12866, and it is not likely to have any adverse effect on 

4351 the supply, distribution, or use of energy. 

4352 I. National Technology Transfer and Advancement Act (NTTAA)

4353 Section 12(d) of the National Technology Transfer and Advancement Act of 1995

4354 (“NTTAA”), Public Law No. 104-113, 12(d) (, 15 U.S.C. 272 note), directs EPA to use 

4355 voluntary consensus standards in its regulatory activities unless to do so would be 

4356 inconsistent with applicable law or otherwise impractical. Voluntary consensus 

4357 standards are technical standards (e.g., materials specifications, test methods, 

4358 sampling procedures, and business practices) that are developed or adopted by 

4359 voluntary consensus standards bodies. NTTAA directs EPA to provide Congress, 

4360 through OMB, explanations when the Agency decides not to use available and 

4361 applicable voluntary consensus standards. This action does not involve technical 

4362 standards. Therefore, EPA did not consider the use of any voluntary consensus 

4363 standards. 

4364 J. Environmental Justice

4365 Executive Order 12898 entitled: Federal Actions to Address Environmental 

4366 Justice in Minority Populations and Low-Income Populations

4367 Executive Order 12898 (59 FR 7629; February 16, 1994) establishes federal 

4368 executive policy on environmental justice. Its main provision directs Federal agencies, 

4369 to the greatest extent practicable and permitted by law, to make environmental justice 

4370 part of their mission by identifying and addressing, as appropriate, disproportionately 

4371 high and adverse human health or environmental effects of their programs, policies, and 

4372 activities on minority populations and low-income populations in the United States. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 176 of 233 

4373 EPA has determined that this final rule will not have disproportionately high and 

4374 adverse human health or environmental effects on minority or low-income populations 

4375 because it increases the level of environmental protection for all affected populations 

4376 without having any disproportionately high and adverse human health or environmental 

4377 effects on any population, including any minority or low-income population. This rule 

4378 only impacts entities that intend to register or currently hold a registration for an 

4379 antimicrobial pesticide. 

4380 XXVI. Congressional Review Act 

4381 The Congressional Review Act, 5 U.S.C. 801 et seq., generally provides that before a 

4382 rule may take effect, the Agency promulgating the rule must submit a rule report to each 

4383 House of the Congress and the Comptroller General of the United States. EPA will 

4384 submit a report containing this rule and other required information to the U.S. Senate, 

4385 the U.S. House of Representatives, and the Comptroller General of the United States 

4386 prior to publication of the rule in the Federal Register. This rule is not a “major rule” as 

4387 defined by 5 U.S.C. 804(2).

4388 List of Subjects in 40 CFR Part 158 

4389 Environmental protection, Administrative practice and procedure, Agricultural 

4390 commodities, Pesticides and pests, Reporting and record keeping requirements. 

4391 List of Subjects in 40 CFR Part 161 

4392 Environmental protection, Administrative practice and procedure, Agricultural 

4393 commodities, Pesticides and pests, Reporting and record keeping requirements. 

4394 Dated: ______________ 

4395 ______________________ 

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

Page 177 of 233 

4397 Therefore, 40 CFR part 158 and part 161 are amended as follows: 

4398 

4399 1. PART 158 [AMENDED}

4400 1. The authority citation for part 158 continues to read as follows: 

4401 Authority: 7 U.S.C. 136-136y and 21 U.S.C. 346a. 

4402 2. Revise § 158.1(c)(4) to read as follows: 

4403 § 158.1 Purpose and scope. 

4404 *****

4405 * * * * *

4406 (c) ***)* * *

4407 (4) Antimicrobial pesticides. Subparts A, B, C, D, and W of this part apply to 

4408 antimicrobial pesticides. 

4409 3. In § 158.100 revise the heading of paragraph (a); revise paragraph (b); 

4410 redesignate paragraph (c) as paragraph (e); and add new paragraphs (c) and (d) to 

4411 read as follows: 

4412 § 158.100. Pesticide use patterns. 

4413 (a).) General use patterns for conventional, biochemical, and microbial 

4414 pesticides. ***.***

4415 (b) Pesticide use site index for conventional, biochemical, and microbial 

4416 pesticides. The Pesticide Use Site Index for Conventional, Biochemical, and Microbial 

4417 Pesticides is a comprehensive list of specific pesticide use sites. The index is 

4418 alphabetized separately by site for all agricultural and all nonagricultural uses. The 

4419 Pesticide Use Site Index associates each pesticide use site with one or more of the 12 

4420 general use patterns. It may be used in conjunction with the data tables to determine 

4421 the applicability of data requirements to specific uses. The Pesticide Use Site Index for 

4422 Conventional, Biochemical, and Microbial Pesticides will be updated periodically, and is 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 178 of 233 

4423 available from the Agency or may be obtained from the Agency's website at 

4424 http://www.epa.gov/pesticides. 

4425 (c) Antimicrobial pesticide use patterns. The general use patterns for 

4426 antimicrobial pesticides are described in § 158.2201. 

4427 (d) Pesticide use site index for antimicrobial pesticides. The Pesticide Use Site 

4428 Index for Antimicrobial Pesticides is a comprehensive list of specific antimicrobial use 

4429 sites. The index is alphabetized by antimicrobial use sites, and associates each 

4430 antimicrobial use site with one or more of the antimicrobial use patterns. It may be used 

4431 in conjunction with the data tables to determine the applicability of data requirements to 

4432 specific uses. The Pesticide Use Site Index for Antimicrobial Pesticides will be updated 

4433 periodically, and is available from the Agency or may be obtained from the Agency’s 

4434 website at http://www.epa.gov/pesticides. 

4435 (e) ***

4436 * * * * *

4437 §158.400 [Amended] 

4438 4. In the table in § 158.400(d) remove the categoryheading “Efficacy of 

4439 Antimicrobial Agents,” and all of the entries 91-2 through 91-8 under that category. 

4440 5. Part 158 is amended by revising Revise subpart W to read as follows: 

4441 Subpart W--Antimicrobial Pesticide Data Requirements 

4442 Sec. 

4443 §158.2200 Applicability. 

4444 §158.2201 Antimicrobial use patterns. 

4445 §158.2203 Definitions. 

4446 §158.2204 Public health and nonpublic health claims. 

4447 §158.2210 Product chemistry. 

4448 §158.2220 Product performance. 

4449 §158.2230 Toxicology. 

4450 §158.2240 Nontarget organisms. 

4451 §158.2250 Nontarget plant protection. 

4452 §158.2260 Applicator exposure. 

4453 §158.2270 Post-application exposure. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 179 of 233 

4454 §158.2280 Environmental fate. 

4455 §158.2290 Residue chemistry. 

4456 § 158.2200 Applicability. 

4457 Part 158, subpart W establishes data requirements for any pesticide product that 

4458 is: 

4459 (a) A pesticide that is intended for use as an “antimicrobial pesticide” within the 

4460 meaning of FIFRA sec. 2(mm)(1)(A), regardless of whether it also meets the criterion of 

4461 FIFRA sec. 2(mm)(1)(B). That criterion excludes from the definition any antimicrobial 

4462 product that is intended for a food-use requiring a tolerance or exemption under FFDCA 

4463 sec. 408 or a food additive regulation or clearance under FFDCA sec. 409. EPA will 

4464 apply this subpart to all products intended for an antimicrobial use, purpose or function; 

4465 the exclusion in FIFRA sec. 2(mm)(1)(B) does not exclude products from the data 

4466 requirements of this subpart. 

4467 (b) A product that bears both antimicrobial and non-antimicrobial uses or claims. 

4468 Such a product is subject to the data requirements for pesticides in subparts C –through

4469 O, and U or V of this part with respect to its non-antimicrobial uses and claims, and to 

4470 the requirements of this subpart W with respect to its antimicrobial uses and claims.

4471 (c) A wood preservative, including a product that is intended to prevent wood 

4472 degradation problems due to fungal rot or decay, sapstain, or molds. 

4473 (d) An antifoulant, including a product that is intended to kill or repel organisms 

4474 that can attach to underwater surfaces, such as boat bottoms. 

4475 § 158.2201 Antimicrobial use patterns.

4476 (a) Antimicrobial use patterns. The 12 general use patterns used in the data 

4477 tables in this subpart are: 

4478 (1) Agricultural premises and equipment. 

4479 (2) Food-handling/storage establishments, premises and equipment. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 180 of 233 

4480 (3) Commercial, institutional and industrial premises and equipment. 

4481 (4) Residential and public access premises. 

4482 (5) Medical premises and equipment. 

4483 (6) Human drinking water systems. 

4484 (7) Materials preservatives. 

4485 (8) Industrial processes and water systems. 

4486 (9) Antifoulant paints and coatings. 

4487 (10) Wood preservatives. 

4488 (11) Swimming pools. 

4489 (12) Aquatic areas. 

4490 (b) Use site index. The Pesticide Use Site Index for Antimicrobial Pesticides is a 

4491 comprehensive list of specific antimicrobial use sites. The Index associates 

4492 antimicrobial use sites with one or more of the 12 antimicrobial use patterns. It is to be 

4493 used in conjunction with the data tables in this subpart to determine the applicability of 

4494 data requirements to specific uses. The Antimicrobial Pesticide Use Site Index, which 

4495 will be updated periodically, is available from the Agency or may be obtained from the 

4496 Agency’s website at http://www.epa.gov/pesticides. 

4497 § 158.2203 Definitions. 

4498 Definitions. The following terms are defined for the purposes of this subpart: 

4499 Disinfectant means a substance, or mixture of substances, that destroys or irreversibly 

4500 inactivates bacteria, fungi and viruses, but not necessarily bacterial spores, in the inanimate 

4501 environment. 

4502 Fungicide means a substance, or mixture of substances, that destroys fungi (including 

4503 yeasts) and fungal spores pathogenic to man or other animals in the inanimate environment. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 181 of 233 

4504 Microbiological water purifier means any unit, water treatment product or system that 

4505 removes, kills or inactivates all types of disease-causing microorganisms from the water, 

4506 including bacteria, viruses and protozoan cysts, so as to render the treated water safe for 

4507 drinking. 

4508 Sanitizer means a substance, or mixture of substances, that reduces the bacteria 

4509 population in the inanimate environment by significant numbers, (e.g., 3 log10 reduction) or more, 

4510 but does not destroy or eliminate all bacteria. Sanitizers meeting Public Health Ordinances are

4511 generally used on food contact surfaces and are termed sanitizing rinses. 

4512 Sterilant means a substance, or mixture of substances, that destroys or eliminates all 

4513 forms of microbial life in the inanimate environment, including all forms of vegetative bacteria, 

4514 bacterial spores, fungi, fungal spores, and viruses. 

4515 Tuberculocide means a substance, or mixture of substances, that destroys or irreversibly 

4516 inactivates tubercle bacilli in the inanimate environment. 

4517 Virucide means a substance, or mixture of substances, that destroys or irreversibly 

4518 inactivates viruses in the inanimate environment. 

4519 § 158.2204 Public health and nonpublic health claims. 

4520 (a) Public health claim. An antimicrobial pesticide is considered to make a public health 

4521 claim if the pesticide product bears a claim to control pest microorganisms that pose a threat to 

4522 human health, and whose presence cannot readily be observed by the user, including but not 

4523 limited to, microorganisms infectious to man in any area of the inanimate environment. A 

4524 product makes a public health claim if one or more of the following apply: 

4525 (1) A claim is made for control of specific microorganisms that are directly or indirectly 

4526 infectious or pathogenic to man (or both man and animals). Examples of specific 

4527 microorganisms include, but are not limited to:,: Mycobacterium tuberculosis, Pseudomonas 

4528 aeruginosa, Escherichia coli (E. coli), human immunodeficiency virus (HIV), Streptococcus, and 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 182 of 233 

4529 Staphylococcus aureus. Claims for control of microorganisms infectious or pathogenic only to 

4530 animals (such as canine distemper virus or hog cholera virus) are not considered public health 

4531 claims. 

4532 (2) A claim is made for the pesticide product as a sterilant, disinfectant, virucide, 

4533 sanitizer, or tuberculocide against microorganisms that are infectious or pathogenic to man. 

4534 (3) A claim is made for the pesticide product as a fungicide against fungi infectious or 

4535 pathogenic to man, or the product does not clearly state that it is intended for use only against 

4536 nonpublic health fungi. 

4537 (4) A claim is made for the pesticide product as a microbiological water purifier or 

4538 microbial purification system. 

4539 (5) A non-specific claim is made that the pesticide product will beneficially impact or 

4540 affect public health at the site of use or in the environment in which it is applied, and: 

4541 (i) The pesticide product contains one or more ingredients that, under the criteria in 40 

4542 CFR 153.125(a), is an active ingredient with respect to a public health microorganism and there 

4543 is no other functional purpose for the ingredient in the product; or 

4544 (ii) The pesticide product is similar in composition to a registered pesticide product that 

4545 makes antimicrobial public health claims. 

4546 (b) Nonpublic health claim. An antimicrobial pesticide is considered to make a 

4547 nonpublic health claim if the pesticide product bears a claim to control microorganisms 

4548 of economic or aesthetic significance, where the presence of the microorganism would 

4549 not normally lead to infection or disease in humans. Examples of nonpublic health 

4550 claims include, but are not limited to,: Algaecides, slimicides, preservatives and 

4551 products for which a pesticidal claim with respect to odor sources is made. 

4552 §158.2210 Product chemistry. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 183 of 233 

4553 The product chemistry data requirements of subpart D of this part apply to 

4554 antimicrobial products covered by this subpart. 

4555 §158.2220 Product performance. 

4556 (a) General. (1) Product performance requirement for all antimicrobial 

4557 pesticides. Each applicant must ensure through testing that his product is efficacious 

4558 when used in accordance with label directions and commonly accepted pest control 

4559 practices. The Agency may require, on a case-by-case basis, submission of product 

4560 performance data for any pesticide product registered or proposed for registration or 

4561 amendment. 

4562 (2) Product performance data for each product that bears a public health claim. 

4563 Each product that bears a public health claim, as described in §158.2204(a), must be 

4564 supported by product performance data, as listed in the table in paragraph (c) of this 

4565 section. Product performance data must be submitted with any application for 

4566 registration or amended registration. 

4567 (3) Product performance data for each product that bears a nonpublic health 

4568 claim. Each product that bears a nonpublic health claim, as described in §158.2204(b), 

4569 must be supported by product performance data. Each registrant must ensure through 

4570 testing that his product is efficacious when used in accordance with label directions and 

4571 commonly accepted practices. The Agency reserves the right to require, on a case-by4572 case basis, submission of product performance data for any pesticide product 

4573 registered or proposed for registration or amendment. 

4574 (4) Determination of data requirements. Subpart B of this part and §158.2201 

4575 describe how to use the table in paragraph (c) of this section to determine the product 

4576 performance data requirements for antimicrobial pesticide products. 

4577 (b) Key. R = Required; EP = End-use product. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 184 of 233 

4578 (c) Antimicrobial product performance data requirements table. 

4579 The following table shows the data requirements for antimicrobial product 

4580 performance. 

4581 Table -- Antimicrobial Product Performance Data Requirements

Guideline 

Number 

Data Requirement All Use Patterns Test Substance 

810.2100 Sterilants – Efficacy Data 

Recommendations 

R EP 

810.2200 Disinfectants for Use on Hard Surfaces – 

Efficacy Data Recommendations 

R EP 

810.2300 Sanitizers for Use on Hard Surfaces – 

Efficacy Data Recommendations 

R EP 

810.2400 Disinfectants and Sanitizers for Use on 

Fabrics and Textiles -- Efficacy Data 

Recommendations 

R EP 

810.2500 Air Sanitizers – Efficacy Data 

Recommendations 

R EP 

810.2600 Disinfectants for Use in Water -- Efficacy 

Data Recommendations 

R EP 

4582 

4583 §158.2230 Toxicology. 

4584 (a) General. Subpart B of this part and § 158.2201 describe how to use the 

4585 table in paragraph (g) of this section to determine the toxicology data requirements for 

4586 an antimicrobial pesticide product. Notes that apply to an individual test including 

4587 specific conditions, qualifications, or exceptions are listed in paragraph (h) of this 

4588 section.

4589 (b) Uses. The applicant for registration must first determine whether the use is 

4590 likely to result in pesticide residues in food or water and therefore consult the “Food 

4591 Use” columns of the table in paragraph (g) of this section. Generally, if the residues of 

4592 the antimicrobial result from an application to a surface or if incorporated into a material 

4593 that may come into contact with food or feed, and residues may be expected to transfer 

4594 to such food or feed, then the “Indirect Food Uses” columns is to be consulted. 

4595 (c) Tiering of data requirements. Applicants for registration of antimicrobials 

4596 may perform tests in a tiered fashion. After the initially required tests are conducted, 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 185 of 233 

4597 additional testing may be required if results of the initial tests trigger the need for 

4598 additional data. Conditions that trigger the need for additional data are given in the test 

4599 notes in paragraph (h) of this section. 

4600 (d) 200 ppb. The 200 ppb level was originally used by the Food and Drug 

4601 Administration with respect to the concentration of residues in or on food for tiering of 

4602 data requirements for indirect food use biocides. The Agency has also adopted this 

4603 same residue level for determining toxicology data requirements for indirect food uses 

4604 of antimicrobial pesticides. The 200 ppb level is the concentration of antimicrobial 

4605 residues in or on the food item. 

4606 (e) Use of OSHA standards. If EPA determines that industrial standards, such as 

4607 the workplace standards set by the Occupational Safety and Health Administration,

4608 (OSHA standards), provide adequate protection for a particular pesticide or a particular 

4609 use pattern, additional toxicity data may not be required for that pesticide or the use 

4610 pattern. 

4611 (f) Key. R = Required; CR = Conditionally required; NR = Not required; MP = 

4612 Manufacturing-use product; EP = End-use product; TGAI = Technical grade of the 

4613 active ingredient; TEP = Typical end-use product; PAI = Pure active ingredient; PAIRA = 

4614 Pure active ingredient, radiolabeled; Choice = choice of several test substances 

4615 depending on studies required. 
*** Deliberative Internal DocumentEO 12866 Draft – Do Not Cite, Quote, or Release ***

During Review ***

Page 186 of 233

4616 (g) Table.Antimicrobial toxicology data requirements table. The following table shows the data 4617 toxicology. The test notes applicable to the data requirements in this table appear in paragraph (h) of 4618 Table -- Antimicrobial Toxicology Data Requirements 

Guideline Number 

Data Requirement Food Uses Nonfood Uses Te

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 MP 

TG

870.1200 Acute dermal toxicity R R R R R MP 

TG

870.1300 Acute inhalation toxicity - rat R R R R R MP 

TG

870.2400 Primary eye irritation - rabbit R R R R R MP 

TG

870.2500 Primary dermal irritation R R R R R MP 

TG

870.2600 Dermal sensitization R R R R R MP 

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 TG870.3150 90-Day oral toxicity - 

nonrodent 

R R CR R CR TG

870.3200 21/28-Day dermal toxicity CR CR CR CR CR TG870.3250 90-Day dermal toxicity CR CR CR CR CR TG870.3465 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 TG870.4200 Carcinogenicity – two rodent R R CR R CR TG
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

Page 187 of 233 

species – rat and mouse preferred 

 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 NR 870.7600 Dermal penetration CR CR CR CR CR Ch870.7800 Immunotoxicity R R R R R TG

4619 
4620 (h) Test notes. The following test notes apply to the data requirements in 

4621 the table to paragraph (g) of this section: 

4622 1. Not required if test material is a gas or highly volatile liquid. 

4623 2. The six end-use product (EP) acute toxicity studies are required using 

4624 the product as formulated for sale and distribution. In addition, if the EP label 

4625 has directions for diluting the product, then, the applicant may also need to 

4626 conduct certain of the acute toxicity studies using the highest concentration 

4627 labeled for dilution (i.e. the least diluted product). The end-use dilution testing is 

4628 in addition to the testing conducted on the EP. 

4629 3. Not required if test material is corrosive to skin or has pH less than 2 or 

4630 greater than 11.5. 

4631 4. Data are required when the product consists of, or under conditions of 

4632 use will result in, a respirable material (e.g., gas, vapor, aerosol or particulates). 

4633 5. Data are required if repeated dermal exposure is likely to occur under 

4634 conditions of use. 

4635 6. For indirect food uses ≤ 200 ppb, and all other nonfood uses, data are 

4636 required if the neurotoxicity screen in the 90-day oral rodent study or other data 

4637 indicate neurotoxicity. 

4638 7. The 90-day dermal toxicity study and/or 90-day inhalation toxicity study 

4639 are required if the Agency determines that dermal and/or inhalation exposure is 

4640 the primary route of exposure. 

4641 8. All 90-day subchronic studies in the rodent can be designed to 

4642 simultaneously fulfill the requirements of the 90-day neurotoxicity and/or 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

*** Deliberative Internal Document – Do NOT Cite, Quote, or Release ***

4643 immunotoxicity studies by adding separate groups of animals for testing of 

4644 neurotoxicity and/or immunotoxicity parameters. 

4645 9. The 90-day study is required in the rodent for hazard characterization 

4646 (possibly endpoint selection) and dose-setting for the chronic/carcinogenicity 

4647 study. It is not required in the mouse, but the Agency would encourage the 

4648 applicant to conduct a 90-day range finding study for the purposes of dose 

4649 selection for the mouse carcinogenicity study to achieve adequate dosing and an 

4650 acceptable study. 

4651 10. A 1-year non-rodent study (i.e., 1-year dog study) may be required if 

4652 the Agency finds that a pesticide chemical is highly bioaccumulative and slowly 

4653 eliminated. EPA may also require the appropriate metabolism and 

4654 pharmacokinetic studies to evaluate more precisely bioavailability, half life, and 

4655 steady state to determine if a longer duration dog toxicity study is needed. 

4656 11. Although the subchronic toxicity testing guidelines include 

4657 measurement of neurological endpoints, such screens do not meet the 

4658 requirement of the 90-day neurotoxicity study. For nonfood uses, if the 90-day 

4659 study does not include a neurotoxicity screen, then the acute neurotoxicity study 

4660 will be required. 

4661 12. Data are required if all of the following criteria are met:

4662 i. The intended use of the antimicrobial pesticide product is expected to 

4663 result in repeated, dermal human exposure to the product,. 

4664 ii. Data from a subchronic 90-day dermal toxicity study are not available, 

4665 and. 

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

*** Deliberative Internal Document – Do NOT Cite, Quote, or Release ***

4667 13. EP testing is required if the product or any component of the product 

4668 may increase dermal absorption of the active ingredient(s) or increases its toxic 

4669 or pharmacologic effects, as determined by testing using the TGAI or based on 

4670 available information about the toxic effects of the product or its components. 

4671 14. Data are required if the active ingredient in the product is known or 

4672 expected to be metabolized differently by the dermal route of exposure than by 

4673 the oral route, and a metabolite of the active ingredient is the toxic moiety. 

4674 15. A 90-day oral toxicity test is not required for heating, ventilation, air 

4675 conditioning, and refrigeration systems (collectively referred to as HVAC&R). 

4676 Instead, two 90-day toxicity tests, one by the dermal route and one by the 

4677 inhalation route are required. 

4678 16. Data are required if there is the likelihood of significant repeated 

4679 inhalation exposure to the pesticide as a gas, vapor, or aerosol. 

4680 17. Based on estimates of the magnitude and duration of human 

4681 exposure, studies of shorter duration, e.g., 21- or 28-days, may be sufficient to 

4682 satisfy this requirement. The prime consideration in determining the 

4683 appropriateness of a shorter duration study is the likely period of time for which 

4684 humans will be exposed. 

4685 18. Based on the positive results of the acute or 90-day neurotoxicity 

4686 studies, or on other data indicating neurotoxicity, a chronic neurotoxicity study 

4687 (i.e..; a chronic study with additional neurotoxicity evaluations) may be required to 

4688 provide information about potential neurotoxic effects from long-term exposures. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

*** Deliberative Internal Document – Do NOT Cite, Quote, or Release ***

4689 19. Studies which are designed to simultaneously fulfill the requirements 

4690 of both the chronic oral and carcinogenicity studies (i.e., a combined study) may 

4691 be conducted. 

4692 20. For indirect food uses ≤ 200 ppb, and all other nonfood uses, data are 

4693 required if either of the following criteria are met: 

4694 i. The use of the pesticide is likely to result in repeated human exposure 

4695 over a considerable portion of the human lifespan; or 

4696 ii. The use requires that a tolerance, tolerance exemption, or food additive 

4697 regulation or clearance be established. 

4698 21. For indirect food uses ≤ 200 ppb, and all other nonfood uses, data are 

4699 required if any of the following criteria, are met: 

4700 i. The use of the pesticide is likely to result in significant human exposure 

4701 over a considerable portion of the human life span which is significant in terms of 

4702 frequency, time, duration, and/or magnitude of exposure. 

4703 ii. The use requires that a tolerance, tolerance exemption, or food additive 

4704 regulation or clearance be established. 

4705 iii. The active ingredient, metabolite, degradate, or impurity: 

4706 A. Is structurally related to a recognized carcinogen; 

4707 B. Causes mutagenic effects as demonstrated by in vitro or in vivo

4708 testing; or 

4709 C. Produces a morphologic effect in any organ (e.g., hyperplasia, 

4710 metaplasia) in subchronic studies that may lead to a neoplastic change. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

*** Deliberative Internal Document – Do NOT Cite, Quote, or Release ***

4711 22. If the requirement for a carcinogenicity study in any species is 

4712 modified or waived for any reason, then a subchronic 90-day oral study in the 

4713 same species may be required. 

4714 23. Testing in two species is required for all uses. 

4715 24. The oral route, by oral intubation, is preferred, unless the chemical or 

4716 physical properties of the test substance, or the pattern of human exposure, 

4717 suggest a more appropriate route of exposure. 

4718 25. Additional testing by other routes of exposure may be required if the 

4719 pesticide is determined to be a prenatal developmental toxicant after oral dosing. 

4720 26. The developmental toxicity study in rodents may be combined with 

4721 the two-generation reproduction study in rodents by using a second mating of the 

4722 parental animals in either generation. Protocols must be approved by the 

4723 Agency prior to the initiation of the study. 

4724 27. A two-generation reproduction study is required. 

4725 28. An information-based approach to testing is preferred, which utilizes 

4726 the best available knowledge on the chemical (hazard, pharmacokinetic, or 

4727 mechanistic data) to determine whether a standard guideline study, an enhanced 

4728 guideline study, or an alternative study should be conducted to assess potential 

4729 hazard to the developing animal. Applicants must submit any alternative 

4730 proposed testing protocols and supporting scientific rationale to the Agency. 

4731 Protocols must be approved by the Agency prior to the initiation of the study. 

4732 29. The use of a combined two-generation reproduction/developmental 

4733 neurotoxicity study that utilizes the two-generation reproduction study in rodents 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

*** Deliberative Internal Document – Do NOT Cite, Quote, or Release ***

4734 as a basic protocol for the addition of other endpoints or functional assessments 

4735 in the immature animal is encouraged. 

4736 30. A DNT study is required using a weight-of-evidence approach when: 

4737 i. The pesticide causes treatment-related neurological effects in adult 

4738 animal studies (i.e, clinical signs of neurotoxicity, neuropathology, functional or 

4739 behavioral effects). 

4740 ii. The pesticide causes treatment-related neurological effects in 

4741 developing animals, following pre- or postnatalpost-natal exposure (i.e., nervous 

4742 system malformations or neuropathy, brain weight changes in offspring, 

4743 functional or behavioral changes in the offspring). 

4744 iii. The pesticide elicits a causative association between exposures and 

4745 adverse neurological effects in human epidemiological studies. 

4746 iv. The pesticide evokes a mechanism that is associated with adverse 

4747 effects on the development of the nervous system (i.e., structure-activity4748 relationship (SAR) to known neurotoxicants, altered neuroreceptor or 

4749 neurotransmitter responses). 

4750 31. To facilitate the weight-of-evidence determination for the pesticide’s 

4751 mutagenicity, the Agency requires submission of other mutagenicity test results, 

4752 besides those specifically listed in this table, that may have been performed. A 

4753 reference list of all studies and papers known to the applicant concerning the 

4754 mutagenicity of the test chemical must be submitted with the required studies. 

4755 32. Due to the nature of antimicrobials, if testing with bacterial strains has 

4756 not been conducted, then testing using a mammalian cell assay such as the 

4757 mouse lymphoma TK +/- assay is preferred. If reverse mutation assay testing 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

*** Deliberative Internal Document – Do NOT Cite, Quote, or Release ***

4758 with bacterial strains has already been conducted, and the testing was conducted 

4759 at levels that did not cause toxicity to the bacterial strains tested, then the 

4760 applicant may submit the study to fulfill this data requirement. 

4761 33. For the in vitro mammalian gene mutation study, there is a choice of 

4762 assays using either mouse lymphoma L5178Y cell thymidine kinase (tk) gene 

4763 locus, maximizing assay conditions for small colony expression and detection; 

4764 Chinese hamster ovary (CHO) or Chinese hamster lung fibroblast (v79) cells, 

4765 hypoxanthine-guanine phosphoribosyl transferase (hgprt) gene locus, 

4766 accompanied by an appropriate in vitro test for clastogenicity; or CHO cells 

4767 strains AS52, xanthine-guanine phosphoribosyl transferase (xprt) gene locus. 

4768 34. There is a choice of assays, but the micronucleus rodent bone 

4769 marrow assay is preferred; the rodent bone marrow assays using metaphase 

4770 analysis (aberrations) are acceptable. 

4771 35. Data are required when chronic toxicity or carcinogenicity studies are 

4772 also required. 

4773 36. Data is required if the product label directs that it be applied to 

4774 domestic animals, such as cats, dogs, cattle, pigs, and horses. 

4775 37. In the absence of dermal absorption data or a repeated dose dermal 

4776 toxicity study, the assumption of 100% dermal absorption would be used in a risk 

4777 assessment to determine if a dermal penetration study is required, and to identify 

4778 the doses and duration of exposure for which dermal absorption is to be 

4779 quantified. 

4780 38. Required for nonfood uses, if oral exposure could occur. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

*** Deliberative Internal Document – Do NOT Cite, Quote, or Release ***

4781 39. Data may be required if significant adverse effects are 

4782 seen in available toxicology studies and these effects can be 

4783 further elucidated by metabolism and pharmacokinetics studies. 

4784 § 158.2240 Nontarget organisms. 

4785 (a) General. Subpart B of this part and § 158.2201 describe how to use 

4786 the table in paragraph (c) of this section to determine the terrestrial and aquatic 

4787 nontarget organisms data requirements for a particular antimicrobial pesticide 

4788 product. Notes that apply to an individual test, including specific conditions, 

4789 qualifications, or exceptions are listed in paragraph (d) of this section. 

4790 (1) Terrestrial and aquatic nontarget organism data are required to 

4791 support the registration of most end-use and manufacturing-use antimicrobial 

4792 products. 

4793 (2) Data are generally not required to support end-use products of a gas, 

4794 highly volatile liquid, highly reactive solid, or a highly corrosive material. 

4795 (3) Data on transformation/degradation products or leachate residues of 

4796 the parent compound are also required to support registration, if the 

4797 transformation/degradation/leachate products meet one of the following criteria: 

4798 (i) More toxic, persistent, or bioaccumulative than the parent; 

4799 (ii) Have been shown to cause adverse effects in mammalian or aquatic 

4800 reproductive studies; or 

4801 (iii) The moiety of concern (i.e., functional group in the parent chemical 

4802 molecule that imparts adverse effects) remains intact. 

4803 (4) If an antimicrobial may be applied to a field crop, horticultural crop, or 

4804 turf, then the data requirements in §158.630 apply. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

*** Deliberative Internal Document – Do NOT Cite, Quote, or Release ***

4805 (5) For the purpose of determining data requirements, the all other use 

4806 patterns category includes the following use patterns: 

4807 (i) Agricultural premises and equipment. 

4808 (ii) Food-handling/storage establishments, premises, and equipment. 

4809 (iii) Commercial, institutional and industrial premises and equipment. 

4810 (iv) Residential and public access premises. 

4811 (v) Medical premises and equipment. 

4812 (vi) Human drinking water systems. 

4813 (vii) Materials preservatives. 

4814 (viii) Swimming pools. 

4815 (b) Key. MP = Manufacturing use product; EP = End-use product; R = 

4816 Required; CR = Conditionally required; NR = Not required; TGAI = Technical 

4817 grade of the active ingredient; TEP = Typical end-use product; PAIRA = Pure 

4818 active ingredient radiolabeled; a.i. = active ingredient. 

4819 
4820 (c) Antimicrobial nontarget organism data requirements table. The following table shows 

4821 requirements for nontarget organisms. The test notes appear in paragraph (d) of this section. 

4822 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 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 lifeR R R R R 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

*** Deliberative Internal Document 

– Do NOT Cite, Quote, or Release ***

Guideline Number 

Data Requirement Use Pattern 

Industrial Processes and Water Systems 

Antifoulant Coatings and Paints 

Wood Preservatives 

Aquatic Areas 

All Other Use Patterns Category 

cycle 

850.1500 Fish life-cycle CR CR CR CR CR 850.1710 850.1730 850.1850 

Aquatic organisms, bioavailability, biomagnification, toxicity tests 

CR CR CR CR CR 

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 freshwater and marine 

CR CR CR CR CR 

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 

4823 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

*** Deliberative Internal Document – Do NOT Cite, Quote, or Release ***

4824 (d) Test notes. The following test notes apply to the data requirements in 

4825 the table to paragraph (c) of this section: 

4826 1. For industrial processes and water systems, antifoulant paints and 

4827 coatings, wood preservatives, and aquatic areas, data are required for two avian 

4828 species: one waterfowl species and one upland game bird species. For the all 

4829 other use patterns category (as specified in § 158.2240(a)(5)), data are required 

4830 for one avian species. 

4831 2. Data are required on one freshwater aquatic invertebrate species. 

4832 3. For the industrial processes and water systems, antifoulant paints and 

4833 coatings, wood preservatives, and aquatic use pattern areas, data are required 

4834 on two species of fish, one coldwater species and one warmwater species. For 

4835 the “All Other” use patterns category (as specified in § 158.2240(a)(5)), data are 

4836 required on onetwo species of fish, either one coldwater species or aand one

4837 warmwater species. Testing on a second species is required if the active 

4838 ingredient or principal transformation products are stable in the environment and 

the LC50 4839 in the first species is greaterless than or equal to 1 ppm or 1 mg/L. 

4840 4. Data are required on one avian species, either one waterfowl species 

4841 or one upland game bird species, if the avian acute oral LD50 ( TGAI testing) is 

4842 less than or equal to 100 mg. a.i./kg and a.i. residues or its principal 

4843 transformation products are likely to occur in avian feed items. Data on the 

4844 second species are required if the avian dietary LC50 in the first species tested is 

4845 less than or equal to 500 ppm a.i. in the diet. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

*** Deliberative Internal Document – Do NOT Cite, Quote, or Release ***

4846 5. If TEP testing cannot be conducted due to the physical characteristics 

4847 of the test substance (for example, a paint), then the applicant should request a 

4848 waiver. 

4849 6. Data are required if one or more of the following criteria are met: 

4850 i. Birds may be subjected to repeated or continued exposure to the 

4851 pesticide or any of its transformation products, especially preceding or during the 

4852 breeding season. 

4853 ii. The pesticide or any of its major metabolites or degradation products 

4854 are stable in the environment to the extent that a potentially toxic amount may 

4855 persist in avian feed. 

4856 iii. The pesticide or any of its major metabolites or degradation products 

4857 are stored or accumulated in plant or animal tissues, as indicated by the 

4858 octanol/water partition coefficient (Kow is greater than or equal to 1,000), 

4859 accumulation studies, metabolic release and retention studies, or as indicated by 

4860 structural similarity to known bioaccumulative chemicals. 

4861 iv. Any other information, such as that derived from mammalian 

4862 reproduction studies, indicates that reproduction in terrestrial vertebrates may be 

4863 adversely affected by the anticipated use of the pesticide product. 

4864 7. TEP testing is required for any product which meets one or more of the 

4865 following conditions: 

4866 i. When based on deterministic modeling results: If the Estimated 

4867 Environmental Concentration (EEC) in the aquatic environment is equal to or 

4868 greater than one-half the LC50/EC50 of the TGAI. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

*** Deliberative Internal Document – Do NOT Cite, Quote, or Release ***

 ii. When based on probabilistic modeling results: If the estimated 10th 4869 

4870 percentile 7Q10 Surface Water Concentration exceeds the acute concentration 

4871 of concern (i.e., one-half the LC50/EC50) for 4 or more days.).

4872 iii. If an ingredient in the end-use product other than the active ingredient 

4873 is expected to enhance the toxicity of the active ingredient or to cause toxicity to 

4874 aquatic organisms. 

4875 iv. The end-use antimicrobial product will be applied directly into an 

4876 aquatic environment. 

4877 8. Data are required on one estuarine/marine mollusk, one other 

4878 estuarine/marine invertebrate, and one estuarine/marine fish species. 

4879 9. For the all other use patterns category (as specified in § 

4880 158.2240(a)(5)), industrial processes and water systems, wood preservatives, 

4881 and aquatic areas, data are required if the pesticide residues from the parent 

4882 compound and/or transformation products are likely to enter the estuarine/marine 

4883 environment. 

4884 10. Testing must be conducted with the most sensitive organism (either 

4885 freshwater or estuarine/marine vertebrates, or freshwater or estuarine/marine 

4886 invertebrates), as determined from the results of the acute toxicity tests (acute 

4887 EC50 freshwater invertebrates; acute LC50/EC50 estuarine and marine organisms; 

4888 acute freshwater fish LC50). 

4889 11. Data are required on estuarine/marine species if the product is 

4890 intended for direct application to the estuarine or marine environment, or the 

4891 product is expected to enter this environment in significant concentrations 

4892 because of its expected use or mobility patterns. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

*** Deliberative Internal Document – Do NOT Cite, Quote, or Release ***

4893 12. Data are required on freshwater species if the end-use product is 

4894 intended to be applied directly to water, or is expected to be transported to water 

4895 from the intended use site, and when one or more of the following conditions 

4896 apply: 

4897 i. When based on deterministic modeling results: If the Estimated 

4898 Environmental Concentration (EEC) in water is equal to or greater than 0.1 of the 

4899 no-observed-adverse-effect concentration or no-observed-adverse-effect level 

4900 (NOAEC/NOAEL) in the fish early-life stage or invertebrate life cycle tests. 

 ii. When based on probabilistic modeling results: If the estimated 10th 4901 

4902 percentile 7Q10 Surface Water Concentration based on probabilistic modeling 

4903 exceeds for 20 days or more the chronic concentration of concern (i.e., one-tenth 

4904 the NOAEC or NOAEL) determined in the fish early-life stage or invertebrate life 

4905 cycle tests. 

4906 iii. If studies of other organisms indicate that the reproductive physiology 

4907 of fish may be affected. 

4908 13. Not required when: 

4909 i. The octanol/water partition coefficients of the pesticide and its major 

4910 degradates are less than 1,000; 

4911 ii. There are no potential exposures to fish and other nontarget aquatic 

4912 organisms; or 

4913 iii. The hydrolytic half-life is less than 5 days at pH 5, 7, and 9. 

4914 14. Environmental chemistry methods used to generate data associated 

4915 with this study must include results of a successful confirmatory method trial by 

4916 an independent laboratory. Test standards and procedures for independent 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

*** Deliberative Internal Document – Do NOT Cite, Quote, or Release ***

4917 laboratory validation are available as addenda to the guideline for this test 

4918 requirement. 

4919 15. Protocols must be approved by the Agency prior to the initiation of the 

4920 study. 

4921 16. Data are required if the intended use pattern, and the 

4922 physical/chemical properties and environmental fate characteristics of the 

4923 antimicrobial indicate significant potential exposure, and, based on the results of 

4924 the acute and chronic aquatic organism testing, significant impairment of 

4925 nontarget aquatic organisms could result. 

4926 17. Data are required if the half-life of the pesticide in the sediment is 

4927 equal to or less than 10 days in either the aerobic soil or aquatic metabolism 

4928 studies, and if one or more of the following conditions are met: 

4929 i. The soil partition coefficient (Kd) is equal to or greater than 50 L/kg. 

4930 ii. The log Kow is equal to or greater than 3. 

4931 iii. The Koc is equal to or greater than 1,000. 

4932 18. Data are required if the EEC in sediment is greater than 0.1 of the 

4933 acute LC50/EC50 values and if one or more of the following conditions are met: 

4934 i. The soil partition coefficient (Kd) is equal to or greater than 50 L/kg. 

4935 ii. The log Kow is equal to or greater than 3. 

4936 iii. The Koc is equal to or greater than 1,000. 

4937 19. Sediment testing with estuarine/marine test species is required if the 

4938 product is intended for direct application to the estuarine or marine environment 

4939 or the product is expected to enter this environment in significant concentrations 

4940 either by runoff or erosion, because of its expected use or mobility pattern. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

*** Deliberative Internal Document – Do NOT Cite, Quote, or Release ***

4941 20. For the all other use patterns category (as specified in § 

4942 158.2240(a)(5)), data are required only for beehive applications when the 

4943 beehive (empty or occupied) may be treated. 

4944 21. A study similar to “Honey Bee Toxicity of Residues on Foliage” is 

4945 required using treated wood instead of the foliage. Protocols must be approved 

4946 by the Agency prior to the initiation of the study. 

4947 §158.2250 Nontarget plant protection. 

4948 (a) Subpart B of this part and § 158.2201 describe how to use the table in 

4949 paragraph (f) of this section to determine the nontarget plant protection data 

4950 requirements for a particular antimicrobial pesticide product. Notes that apply to 

4951 an individual test including specific conditions, qualifications, or exceptions are 

4952 listed in paragraph (g) of this section. 

4953 (b) Data on transformation/degradation products or leachate residues of 

4954 the parent compound are also required to support registration, if the 

4955 transformation/degradation/leachate products meet one of the following criteria: 

4956 (i1) More toxic, persistent, or bioaccumulative than the parent; 

4957 (ii2) Have been shown to cause adverse effects in mammalian or aquatic 

4958 reproductive studies; or 

4959 (1) (iii) The moiety of concern (i.e., functional group in the parent 

4960 chemical molecule that imparts adverse effects) remains intact.

4961 (3) The moiety of concern (i.e., functional group in the parent chemical 

4962 molecule that imparts adverse effects) remains intact.

4963 (c) For the purpose of determining data requirements, the all other use 

4964 patterns category includes the following use patterns: 

4965 (i1) Agricultural premises and equipment. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

*** Deliberative Internal Document – Do NOT Cite, Quote, or Release ***

4966 (ii2) Food-handling/storage establishments, premises, and equipment. 

4967 (iii3) Commercial, institutional and industrial premises and equipment. 

4968 (iv4) Residential and public access premises. 

4969 (v5) Medical premises and equipment. 

4970 (vi6) Human drinking water systems. 

4971 (vii7) Materials preservatives. 

4972 (viii8) Swimming pools. 

4973 (d) If an antimicrobial may be applied to a field crop, horticultural crop, or 

4974 turf, then the data requirements in 40 CFR 158.660 apply. 

4975 (e) Key. MP = Manufacturing use product; EP = End-use product; R = 

4976 Required; CR = Conditionally required; NR = Not required; TGAI = Technical 

4977 grade of the active ingredient; TEP = Typical end-use product. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

*** Deliberative Internal Document 

– Do NOT Cite, Quote, or Release ***

4978 (f) Nontarget plant protection data requirements table. The following table shows the data requ

4979 nontarget plant protection. The test notes appear in paragraph (g) of this section. 

4980 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 

850.4300 Terrestrial field CR CR CR CR CR 850.4450 Aquatic field CR CR CR CR CR 

4981 
4982 (g) Test notes. The following test notes apply to the data requirements in 

4983 the table to paragraph (f) of this section: 

4984 1. Data on only one plant species (rice, Oryza sativa) are required. 

4985 2. Data are required if the risk quotient from any aquatic plant growth Tier 

4986 II study exceeds a level of concern for aquatic plants. 

4987 3. Not required when: 

4988 i. There are no potential exposures to plants; 

4989 ii. The hydrolytic half-life is less than 5 days at pH 5, 7, and 9; or 

4990 iii. The results of a biodegradation study indicate that the active ingredient 

4991 or principal degradation products are not biodegradable in 28 days, i.e. the 

4992 biodegradation curve has not reached a plateau for at least three determinations 

4993 within the 28 days. 

4994 4. For TEP testing, data are required for the applicant’s end-use product 

4995 if an ingredient in the end-use product, other than the active ingredient, is 

4996 expected to enhance the toxicity of the active ingredient. 

4997 5. One Tier II (dose response) study, conducted with Selenastrum 

4998 capricornutum, is required for the all other use patterns category (as specified in 

4999 § 158.2250(c)). If the results of this study exhibit detrimental effects (EC50 less 

5000 than 1.0 ppm or mg/L), then additional Tier II (dose response) studies are 

5001 required on three species (Anabaena flos-aquae, Navicula pelliculosa, and 

5002 Skeletonema costatum).

5003 6. For industrial processes and water systems, antifoulant coatings and 

5004 paints, wood preservatives, and aquatic areas, Tier II (dose response) studies 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

*** Deliberative Internal Document – Do NOT Cite, Quote, or Release ***

5005 are required on four species (Anabaena flos-aquae, Navicula pelliculosa, 

5006 Skeletonema costatum, and Selenastrum capricornutum). 

5007 7. Environmental chemistry methods used to generate data must include 

5008 the results of a successful confirmatory method trial by an independent 

5009 laboratory. 

5010 8. Tests are required on a case-by-case basis based on the results of 

5011 lower tier plant protection studies, adverse incident reports, intended use pattern, 

5012 and environmental fate characteristics that indicate potential exposure. 

5013 9. Protocols must be approved by the Agency prior to the initiation of the 

5014 study. 

5015 10. For the all other use patterns category (as specified in § 158.2250(c)), 

5016 data are required if the aquatic (algal) plant growth Tier II study demonstrates 

5017 detrimental effects at less than 1.0 ppm or mg/L.

5018 §158.2260 Applicator exposure. 

5019 (a) General. Subpart B of this part and § 158.2201 describe how to use 

5020 the table in paragraph (d) of this section to determine the applicator exposure 

5021 data requirements for antimicrobial pesticide products. Notes that apply to an 

5022 individual test including specific conditions, qualifications, or exceptions are listed 

5023 in paragraph (e) of this section. 

5024 (1) The Agency may accept surrogate exposure data estimations and/or 

5025 modeling estimations from other sources to satisfy exposure data requirements. 

5026 The surrogate data must meet the basic quality assurance, quality control, good 

5027 laboratory practice, and other scientific requirements set by EPA. To be 

5028 acceptable, the Agency must find that the surrogate exposure data estimations 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

*** Deliberative Internal Document – Do NOT Cite, Quote, or Release ***

5029 have adequate information to address the applicable exposure data requirements 

5030 and contain adequate monitoring events of acceptable quality. The data must 

5031 reflect the specific use prescribed on the label and the activity of concern, 

5032 including formulation type, application methods and rates, type of activity, and 

5033 other pertinent information. 

5034 (2) Occupational uses include not only handlers, mixers, loaders, and 

5035 applicators, but also commercial applications to residential sites. Residential 

5036 uses are limited to non-occupational, i.e., non-professional, antimicrobial 

5037 applications. Both occupational and residential applicator data may be required 

5038 for the same product. 

5039 (b) Criteria for testing. Applicator exposure data described in the table to 

5040 paragraph (d) of this section are required based on toxicity and exposure criteria. 

5041 Data are required if at least one of the toxicity criteria in paragraph (b)(1) of this 

5042 section, and at least one of the exposure criteria in paragraph (b)(2) of this 

5043 section are met. 

5044 (1) Toxicity criteria. (i) Evidence of potentially significant adverse effects 

5045 have been observed in any applicable toxicity studies. 

5046 (ii) Scientifically sound epidemiological or poisoning incident data with a 

5047 clear cause-effect relationship indicating that adverse health effects may have 

5048 resulted from exposure to the pesticide. 

5049 (2) Exposure criteria.--(i) Dermal exposure may occur during product 

5050 use. 

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

*** Deliberative Internal Document – Do NOT Cite, Quote, or Release ***

5052 (c) Key. R = Required; CR = Conditionally required; TEP = Typical end5053 use product.

5054 (d) Antimicrobial applicator exposure data requirements table. The 

5055 following table shows the data requirements for applicator exposure. The test 

5056 notes appear in paragraph (e) of this section. 

5057 Table -- Antimicrobial Applicator Exposure Data Requirements 

Guideline 

Number 

Data Requirements Use Sites Test 

Substance 

Test Note 

No. 

Occupational Residential 

875.1100 

875.1200 

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

875.1300 

875.1400 

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

875.1500 Biological monitoring CR CR TEP 1, 2, 3 

875.1600 Data reporting and 

calculations 

R R TEP 5 

875.1700 Product use information R R TEP -- 

5058 

5059 (e) Test notes. The following test notes apply to the data requirements in 

5060 the table to paragraph (d) of this section: 

5061 1. Prior to initiation of the study, protocols involving intentional exposure 

5062 of human subjects must be submitted for review by EPA and then the Human 

5063 Studies Review Board (HSRB) according to 40 CFR 26.1125. Examples of 

5064 proposed human study research can be found in various reviews provided by the 

5065 Human Studies Review Board (http://www.epa.gov/osa/hsrb/index.htm). 

5066 2. Biological monitoring data may be submitted in addition to, or in lieu of, 

5067 dermal and inhalation passive dosimetry exposure data, provided the human 

5068 pharmacokinetics of the pesticide or metabolite/analog compounds (i.e., 

5069 whichever method is selected as an indicator of body burden or internal dose) 

5070 allow for the back calculation to the total internal dose. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

*** Deliberative Internal Document – Do NOT Cite, Quote, or Release ***

5071 3. For products with both indoor and outdoor uses, and similar conditions 

5072 of use, data are generally required for the indoor applications only. However, 

5073 data for outdoor uses are required if the Agency expects outdoor uses to result in 

5074 greater exposure than indoor uses (e.g., higher use rates and application 

5075 frequency, or longer exposure duration, or application methods/equipment create 

5076 potential for increased dermal or inhalation exposure in outdoor versus indoor 

5077 use sites). In certain cases, when a pesticide may be used both indoors and 

5078 outdoors under dissimilar conditions of use, the Agency may require submission 

5079 of applicator exposure data for both use patterns. 

5080 4. EPA will consider waiving this data requirement for antimicrobials 

5081 applied via closed loading systems if the antimicrobial has a low vapor pressure. 

5082 5. Data reporting and calculations are required only if handler exposure 

5083 data are required. 

5084 §158.2270 Post-application exposure. 

5085 (a) General. Subpart B of this part and § 158.2201 describe how to use 

5086 the table in paragraph (d) of this section to determine the post-application 

5087 exposure data requirements for antimicrobial pesticide products. The data 

5088 generated during these studies are used to determine the quantity of pesticide to 

5089 which people may be exposed after application. Notes that apply to an individual 

5090 test, including specific conditions, qualifications, or exceptions to the designated 

5091 test, are listed in paragraph (e) of this section. 

5092 (1) Post-application exposure data are required when certain toxicity 

5093 criteria are met and the human activities associated with the pesticide's use 

5094 pattern can lead to potential adverse exposures. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

*** Deliberative Internal Document – Do NOT Cite, Quote, or Release ***

5095 (2) The Agency may accept surrogate exposure data estimations and/or 

5096 modeling estimations from other sources to satisfy exposure data requirements. 

5097 The surrogate data must meet the basic quality assurance, quality control, good 

5098 laboratory practice, and other scientific requirements set by EPA. To be 

5099 acceptable, the Agency must find that the surrogate exposure data estimations 

5100 have adequate information to address the applicable exposure data requirements 

5101 and contain adequate monitoring events of acceptable quality. The data must 

5102 reflect the specific use prescribed on the label and the activity of concern, 

5103 including formulation type, application methods and rates, type of activity, and 

5104 other pertinent information. 

5105 (b) Criteria for testing. Post-application exposure data described in the 

5106 table to paragraph (d) of this section are required based on toxicity and exposure 

5107 criteria. Data are required if at least one of the toxicity criteria in paragraph (b)(1) 

5108 of this section, and at least one of the exposure criteria in paragraph (b)(2) of this 

5109 section are met. 

5110 (1) Toxicity criteria.--(i) Evidence of potentially significant adverse effects 

5111 have been observed in any applicable toxicity studies. 

5112 (ii) Scientifically sound epidemiological or poisoning incident data with a 

5113 clear cause-effect relationship indicating that adverse health effects may have 

5114 resulted from exposure to the pesticide. 

5115 (2) Exposure criteria. --(i) Outdoor uses. (A) Occupational human post5116 application or bystander exposure to residues of antimicrobial pesticides could 

5117 occur as the result of, but is not limited to, worker re-entry into treatment sites, 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

*** Deliberative Internal Document – Do NOT Cite, Quote, or Release ***

5118 clean-up and equipment maintenance tasks, handling wood preservative-treated 

5119 wood, or other work-related activity. 

5120 (B) Residential human post-application or bystander exposure to residues 

5121 of antimicrobial pesticides could occur following the application of antimicrobials

5122 pesticides to outdoor areas and spaces at residential sites, such as, but not 

5123 limited to homes, daycare centers, and other public buildings. 

5124 (ii) Indoor uses. (A) Occupational human post-application or bystander 

5125 exposure to pesticide residues could occur following the application of the 

5126 antimicrobial pesticide to indoor spaces or surfaces. 

5127 (B) Residential human post-application or bystander exposure to 

5128 pesticide residues could occur following the application of the antimicrobial 

5129 pesticide to indoor spaces or surfaces at residential sites, such as, but not limited 

5130 to homes, daycare centers, hospitals, schools, and other public buildings. 

5131 (c) Key. R = Required; CR = Conditionally required; NR = Not required; 

5132 TEP = Typical end-use product. 

5133 (d) Antimicrobial post-application exposure data requirements table. The 

5134 following table shows the data requirements for post-application exposure. The 

5135 test notes appear in paragraph (e) of this section. 

5136 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 --- 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

*** Deliberative Internal Document – Do NOT Cite, Quote, or Release ***

875.2800 Description of 

human activity 

R R TEP --- 

875.2900 Data reporting and 

calculations 

R R TEP 10 

5137 

5138 (e) Test notes. The following test notes apply to the data requirements in 

5139 the table to paragraph (d) of this section: 

5140 1. Prior to initiation of the study, protocols involving intentional exposure 

5141 of human subjects must be submitted for review by EPA and then the Human 

5142 Studies Review Board (HSRB) according to 40 CFR 26.1125. Examples of 

5143 proposed human study research can be found in various reviews provided by the 

5144 Human Studies Review Board (HSRB) (http://www.epa.gov/osa/hsrb/index.htm). 

5145 2. For residential wood preservative uses, data may be required if soil has 

5146 the potential to be an important exposure pathway, and soil is in contact with or 

5147 adjacent to treated wood, including but not limited to decks, play sets, and 

5148 gazebos, 

5149 3. Protocols must be approved by the Agency prior to the initiation of the 

5150 study. 

5151 4. For wood preservatives, data are required for treated wood surfaces 

5152 where post-application contact with treated wood is anticipated. 

5153 5. For occupational uses, data are required if the pesticide may be 

5154 applied to or around surfaces, and if the human activity data indicate that workers 

5155 are likely to have post-application dermal contact with treated surfaces while 

5156 participating in typical activities. 

5157 6. Data are required for residential use sites, schools, and daycare 

5158 institutions. This includes but is not limited to the following: Residential and 

5159 public access premises; material preservatives (including those used in 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

*** Deliberative Internal Document – Do NOT Cite, Quote, or Release ***

5160 residential products, including but not limited to clothing and plastic toys) and 

5161 wood preservatives (when contact with treated wood is likely to occur). 

5162 7. Data are required for occupational and residential uses if the human 

5163 activity data indicate the potential for post-application dermal and/or inhalation 

5164 exposures while participating in typical activities and no acceptable modeling 

5165 options are available. 

5166 8. Biological monitoring data may be submitted in addition to, or in lieu of, 

5167 dermal and inhalation passive dosimetry exposure data provided the human 

5168 pharmacokinetics of the pesticide or metabolite/analog compounds (i.e., 

5169 whichever method is selected as an indicator of body burden or internal dose) 

5170 allow for a back-calculation to the total internal dose. 

5171 9. Data are required for occupational and residential uses if there is the 

5172 potential for bystander exposure and the pesticide use could result in respirable 

5173 and/or inhalable material (e.g., gas, vapor, aerosol, or particulates). 

5174 10. Data reporting and calculations are required only if post-application 

5175 exposure data are required. 

5176 §158.2280 Environmental fate. 

5177 (a) General. Subpart B of this part and § 158.2201 describe how to use 

5178 the table in paragraph (c) of this section to determine the environmental fate data 

5179 requirements for antimicrobial pesticide products. Notes that apply to an 

5180 individual test including specific conditions, qualifications, or exceptions are listed 

5181 in paragraph (d) of this section. 

5182 (1) Environmental fate data are required to support the registrations of all 

5183 end-use and manufacturing-use antimicrobial products. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

*** Deliberative Internal Document – Do NOT Cite, Quote, or Release ***

5184 (2) Data on transformation/degradation products or leachate residues of 

5185 the parent compound are also required to support registration, if the 

5186 transformation/degradation/leachate products meet one of the following criteria: 

5187 (i) More toxic, persistent, or bioaccumulative than the parent; 

5188 (ii) Have been shown to cause adverse effects in mammalian or aquatic 

5189 reproductive studies; or 

5190 (iii) The moiety of concern (i.e., functional group in the parent chemical 

5191 molecule that imparts adverse effects) remains intact. 

5192 (3) For the purpose of determining data requirements, the “All Other”all 

5193 other use patterns category includes the following use patterns: 

5194 (i) Agricultural premises and equipment. 

5195 (ii) Food-handling/storage establishments, premises, and equipment. 

5196 (iii) Commercial, institutional and industrial premises and equipment. 

5197 (iv) Residential and public access premises. 

5198 (v) Medical premises and equipment. 

5199 (vi) Human drinking water systems. 

5200 (vii) Materials preservatives. 

5201 (viii) Swimming pools.

5202 (b) Key . MP = Manufacturing use product; EP = End-use product; R = 

5203 Required; CR = Conditionally required; NR = Not required; TGAI = Technical 

5204 grade of the active ingredient; TEP = Typical end-use product; PAIRA = Pure 

5205 active ingredient radiolabeled; ROC = residue of concern. 
5206 (c) Antimicrobial environmental fate data requirements table. The following table shows the dat

5207 environmental fate. The test notes appear in paragraph (d) of this section. 

5208 Table -- Antimicrobial Environmental Fate Data Requirements 

Guideline Number 

Data Requirement Use Pattern Test Subs

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 

835.3110 Ready 

Biodegradability 

CR CR CR NR CR TGAI 

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

*** Deliberative Internal Document 

– Do NOT Cite, Quote, or Release ***

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 

835.4300 Aerobic aquatic 

metabolism 

R R R R CR TGAI or 

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

5209 (d) Test notes. The following test notes apply to the data requirements in 

5210 the table in paragraph (c) of this section: 

5211 1. For testing antifoulant paints and coatings, testing is to be performed 

5212 separately with both sterile buffered distilled water and sterile synthetic seawater 

5213 at pHs 5, 7, and 9. 

5214 2. Not required if: 

5215 (i). The electronic absorption spectra, measured at pHs 5, 7 and 9, of the 

5216 chemical and its hydrolytic products, if any, show no absorption or tailing 

5217 between 290 and 800 nm, inclusive; or 

5218 (ii). The results of the hydrolysis study at all three pHs (5, 7, and 9) 

5219 demonstrates a half-life of less than 30 days. 

5220 3. The results of the activated sludge, respiration inhibition (ASRI) test 

5221 determine which of the following tests are required: Ready biodegradability, 

5222 porous pot, the biodegradation in activated sludge study as described in the 

5223 “Simulation Tests to Assess the Biodegradability of Chemicals Discharged in 

5224 Wastewater,” or simulation test – aerobic sewage treatment: A. activated sludge 

5225 units. 

5226 (i).. If the ASRI test EC50 is equal to or less than 20 mg/L, then the 

5227 applicant must choose either to: 

5228 (A).. Conduct the biodegradation in activated sludge study as described in 

5229 the “Simulation Tests to Assess the Biodegradability of Chemicals Discharged in 

5230 Wastewater”; 

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

5232 (C).. Conduct the simulation test – aerobic sewage treatment: A. activated 

5233 sludge units. 

5234 (ii).. If the ASRI test EC50 is greater than 20 mg/L, then the applicant must 

5235 choose either to: 

5236 (A).. Conduct a ready biodegradability study; or 

5237 (B).. Conduct one of the following studies: The biodegradation in 

5238 activated sludge study as described in the “Simulation Tests to Assess the 

5239 Biodegradability of Chemicals Discharged in Wastewater,” the porous pot test, or 

5240 the simulation test – aerobic sewage treatment: A. activated sludge units. 

5241 4. Pass criteria for the ready biodegradability study are: 70% removal of 

5242 dissolved organic carbon (DOC) and 60% removal of theoretical oxygen demand 

5243 (ThOD) or theoretical carbon dioxide (ThCO2) production for respirometric 

5244 methods. These pass levels must be reached in a 10-day window within the 28-

5245 day period of the test. If the antimicrobial passes the ready biodegradability 

5246 study, then no further testing is required. If the antimicrobial fails the ready 

5247 biodegradability study, then the applicant must conduct one of the following 

5248 studies: The biodegradation in activated sludge study as described in the 

5249 “Simulation Tests to Assess the Biodegradability of Chemicals Discharged in 

5250 Wastewater,” the porous pot test, or the simulation test – aerobic sewage 

5251 treatment: A. activated sludge units. 

5252 5. For the all other use patterns category (as specified in § 

5253 158.2280(a)(3)), data are required based on a weight-of-evidence evaluation of 

5254 the results of the hydrolysis, photodegradation in water, activated sludge sorption 

5255 isotherm, biodegradability, and activated sludge, respiration inhibition tests. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

5256 6. Adsorption and desorption using a batch equilibrium method is 

5257 preferred. In some cases, as when the antimicrobial pesticide degrades rapidly, 

5258 soil column leaching with unaged or aged columns may be more appropriate to 

5259 fully characterize the potential mobility of the parent compound and major 

5260 transformation products. 

5261 7. For industrial processes and water systems, aquatic areas, and the all 

5262 other use patterns category (as specified in § 158.2280(a)(3)), data are required 

5263 based on a weight-of-evidence evaluation of the results of the hydrolysis, 

5264 photodegradation in water, activated sludge sorption isotherm, biodegradability, 

5265 and activated sludge, respiration inhibition tests. 

5266 8. The environmental media (soil, water, hydrosoil, and biota) to be 

5267 utilized in these studies must be collected from areas representative of potential 

5268 use sites. 

5269 9. For industrial processes and water systems, and aquatic areas, data 

5270 are required for use sites that are intermittently dry. 

5271 10. For non-metallic antimicrobials, Data are not required if the antimicrobial is 

5272 an inorganic substance or a metal salt; or if the standardized soil profiles 

5273 demonstrate that the antimicrobial is likely to readily degrade either microbially or 

5274 via redox reactions (chemically).) and no transformation/degradate/leachate 

5275 products of concern (as described under § 158.2280(a)(2)) are produced. 

5276 11. Analytical methods used to generate data associated with this study 

5277 must include results of a successful confirmatory method trial by an independent 

5278 laboratory. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

5279 12. Protocols must be approved by the Agency prior to the initiation of the 

5280 study. 

5281 13. For industrial processes and water systems, wood preservatives, and 

5282 the all other use patterns category (as specified in § 158.2280(a)(3)), data are 

5283 required based on the potential for aquatic exposure and if the weight-of5284 evidence indicates that the active ingredient or principal transformation products 

5285 are likely to have the potential for persistence, mobility, nontarget aquatic toxicity, 

5286 or bioaccumulation. 

5287 14. Data are required if the weight-of-evidence indicates that the active 

5288 ingredient or principal transformation products are likely to occur in nontarget 

5289 freshwater, estuarine, or marine waters such that human or environmental 

5290 exposures are likely to occur. In making that determination, the Agency takes 

5291 into account other factors such as the toxicity of the chemical(s), available 

5292 monitoring data and the vulnerability of the freshwater, estuarine, or marine water 

5293 resources in the antimicrobial use area. 

5294 15. For wood preservatives, an aquatic leaching study is required. A soil 

5295 leaching study is required if human or environmental exposures are likely to 

5296 occur from leachates that contain the active ingredient or principal transformation 

5297 products from wood treated with a preservative product. Protocols must be 

5298 approved by the Agency prior to the initiation of the study. 

5299 16. For antifoulant paints and coatings, a leaching study is required. 

5300 Protocols must be approved by the Agency prior to the initiation of the study. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

5301 17. Protocols, which include the residues of concern (such as parent, 

5302 degradate/transformation product, and/or leachate residues) that would be 

5303 monitored, must be approved by the Agency prior to the initiation of the study. 

5304 18. A biodegradation study is not required if the antimicrobial meets one 

5305 or more of the following criteria: 

5306 i. Classified as a metal;,

5307 ii. Relatively volatile, but not hydrophobic;, 

5308 iii. Highly reactive,

5309 iv. Both the parent and all transformation/degradate products (as 

5310 described under § 158.2280(a)(2)) have half-lives of less than 3 hours,

5311 v. None of the registered or proposed product uses would result in 

5312 transport of the parent and its transformation/degradate products (as described 

5313 under § 158.2280(a)(2)) to a wastewater treatment plant. 

5314 19. The activated sludge sorption isotherm test is not required if the 

5315 antimicrobial is: 

5316 i. Relatively volatile, but not hydrophobic; 

5317 ii. Highly reactive; or 

5318 iii. The log Kow is less than 3.0. 

5319 20. If the criteria of test note (19) of this paragraph are not met, then the 

5320 activated sludge sorption isotherm test is required if one or more of the following 

5321 criteria are also met: 

5322 i. The antimicrobial is a metal.,

5323 ii. The log Kow is greater than or equal to 3.0.,

5324 iii. The antimicrobial is positively charged or polycationic.,
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

5325 iv. The EC50 in the activated sludge, respiration inhibition test is less than 

5326 or equal to 20 mg/L.,

5327 v. The EC50 in the activated sludge, respiration inhibition test is greater 

5328 than 20 mg/L, and the antimicrobial fails the ready biodegradability study. 

5329 21. The activated sludge respiration inhibition study is not required if none 

5330 of the registered or proposed product uses would result in transport of the parent 

5331 and its transformation/degradate products (as described under § 158.2280(a)(2)) 

5332 to a wastewater treatment plant.

5333 § 158.2290 Residue Chemistry 

5334 (a) General. Subpart B of this part and §158.2201 describe how to use 

5335 the table in paragraph (h) of this section to determine the residue chemistry data 

5336 requirements for antimicrobial pesticide products. Notes that apply to an 

5337 individual test including specific conditions, qualifications, or exceptions are listed 

5338 in paragraph (i) of this section. 

5339 (b) Residue chemistry data are required for: 

5340 (1) Antimicrobial end-use products with uses that may result in residues in 

5341 or on food including, but not limited to: 

5342 (i) Products that require a tolerance, tolerance exemption, or food additive 

5343 regulation or clearance. 

5344 (ii) Products that may be used to treat livestock or poultry drinking water, 

5345 for food egg washing, or for fruit and vegetable rinses. 

5346 (iii) Products that may be applied to a surface or incorporated into a 

5347 material that may contact food or feed. Data are required regardless of whether 

5348 the antimicrobial is applied or impregnated for the purpose of imparting 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

5349 antimicrobial protection to external surfaces of the substance or article, or for the 

5350 purpose of protecting the substance or article itself. 

5351 (iv) Products that may be applied to water that have the potential to result 

5352 in residues in potable water, or in water used for livestock and poultry drinking 

5353 water, irrigation of crops, or water containing fish that may be used for human 

5354 food. 

5355 (v) Wood preservative or antifoulant products intended for treating 

5356 submerged materials that may result in food contact (e.g., lobster pots, fish 

5357 cages on fish farms). 

5358 (2) Each manufacturing-use product bearing directions for formulation into 

5359 an end-use product bearing uses described in paragraph (b)(1) of this section. 

5360 (c) Residue chemistry data are not required under paragraph (b) of this 

5361 section if no adverse effects (no toxicity endpoints) are associated with dietary 

5362 exposure to the active ingredient or if theoretical (high-end) dietary exposure 

5363 estimates combined with the applicable toxicity endpoint result in acute and 

5364 chronic dietary risks that are below the Agency levels of concern. 

5365 (d) For purposes of this section, Magnitude of the Residue Studies 

5366 include the following: Food-handling, migration studies, potable water, fish, 

5367 irrigated crops, meat/milk/poultry/eggs, crop field trails, processed food or feed, 

5368 and anticipated residues. 

5369 (e) If the antimicrobial chemical may be applied to a field crop, then the 

5370 residue chemistry data requirements of §158.1410 apply. 

5371 (f) The following term is defined for the purposes of this section: 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

5372 Residue of concern means the parent pesticidal compound and its metabolites, 

5373 degradates, and impurities of toxicological concern. 

5374 (g) Key. R = Required; CR = Conditionally required; NR = Not required; 

5375 TGAI = Technical grade of the active ingredient; TEP = Typical end-use product; 

5376 PAI = Pure active ingredient; PAIRA = Pure active ingredient radiolabeled; ROC 

5377 = Residue of concern.
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

5378 (h) Antimicrobial residue chemistry data requirements table. The following table shows the dat

5379 residue chemistry. The test notes appear in paragraph (i) of this section. 

5380 Table -- Antimicrobial Residue Chemistry Data Requirements 

Guideline Number 

Data Requirement Uses Test 

Substa

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 None 

Nature of residue on surfaces CR CR CR CR 

PAIRA TGAI 

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 o

Higher tiered 

860.1300 

Nature of the residue in plants CR CR CR CR PAIRA 

860.1300 

Nature of the residue in livestock CR CR CR CR PAIRA 

860.1340 

Residue analytical methods for tolerance/tolerance 

CR CR CR CR ROC 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

exemption enforcement 

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 

860.1500 Crop field trials CR CR CR CR TEP 860.1520 Processed food or 

feed 

CR CR CR CR TEP 

None Anticipated residues CR CR CR CR ROC 

5381 
5382 (i) Test notes. The following test notes apply to the data requirements in 

5383 the table to paragraph (h) of this section: 

5384 1. A petition proposing a numerical tolerance or a tolerance exemption is 

5385 required for any food or feed use subject to section 408 of FFDCA if the use is 

5386 not covered by an existing tolerance or tolerance exemption. If the use is subject 

5387 to FFDCA section 409, the applicant must identify to EPA an applicable section 

5388 409 food additive regulation or clearance, or submit a copy of a petition to FDA 

5389 requesting a section 409 food additive regulation or clearance for the food or 

5390 feed use. 

5391 2. An analytical reference standard is required for any food or feed use 

5392 requiring a numeric tolerance or exemption. Material safety data sheets as 

5393 specified by the Occupational Safety and Health Administration in 29 CFR 

5394 1910.1200 must accompany analytical standards. 

5395 3. Data are required if a pesticide may be used in a food-handling 

5396 establishment unless data including, but not limited to, theoretical (high-end) 

5397 estimates, radiolabeled laboratory data, or the nature of the residue on surfaces 

5398 study show that residues will not occur in food or feed. 

5399 4. If an antimicrobial pesticide may be applied to a food-contact surface or 

5400 impregnated into a food-contact material and if theoretical (high-end) estimates 

5401 of exposure exceed EPA’s risk level of concern, then the nature of the residue on 

5402 surfaces study is required. Protocols must be approved by the Agency prior to 

5403 the initiation of the study. 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

5404 5. Based on the results of the nature of the residue on surfaces study, if 

5405 residues of concern are identified, then the migration study will be required. 

5406 Protocols must be approved by the Agency prior to the initiation of the study. 

5407 6. If a magnitude of the residue study, as specified in § 158.2290(d), is 

5408 required, then a residue analytical method suitable for collecting data is also 

5409 required. The method must be capable of determining all residues of concern, to 

5410 permit calculation of dietary risk or to establish a tolerance or tolerance 

5411 exemption. 

5412 7. If a magnitude of the residue study, as specified in § 158.2290(d), is 

5413 required, then storage stability data are also required, unless analytical samples 

5414 are stored for 30 days or less. If, during hazard characterization, a residue has 

5415 been identified as “of concern” and is known to be volatile or labile, then storage 

5416 stability data are required regardless of sample storage time. 

5417 8. If crop plants or metabolically active raw agricultural commodities of 

5418 food crops may be directly or indirectly exposed to an antimicrobial, plant 

5419 metabolism studies are required to determine the transformation products that 

5420 may enter the human diet. Such exposure could include, but is not limited to: 

5421 i. Treatment of storage or shipping containers, 

5422 ii. Postharvest fruit and vegetable treatment prior to shipping or storage, 

5423 iii. Use of antimicrobial-treated water for irrigation, and 

5424 iv. Any direct food contact use. 

5425 9. If livestock may be exposed to an antimicrobial, then hen and ruminant 

5426 metabolism studies are required to determine the identities of residues of 

5427 concern that may enter the human diet from consumption of livestock 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

5428 commodities. Livestock may be exposed via the oral, dermal, or inhalation route 

5429 following treatment or contamination of sites including, but not limited to, 

5430 livestock premises, feed, and drinking water. Shell eggs and other metabolically 

5431 active livestock products may also be treated. If livestock may be exposed to 

5432 one or more residues of concern differing from those found in animals, then one 

5433 or more additional livestock metabolism studies involving dosing with these 

5434 residues may be required. 

5435 10. If there is a numerical tolerance or tolerance exemption level to 

5436 enforce, then a residue analytical method suitable for enforcement purposes is 

5437 required. The method must be supported by an independent laboratory 

5438 validation. 

5439 11. If there is a numerical tolerance or tolerance exemption level to 

5440 enforce, then testing is required to determine whether the Food and Drug 

5441 Administration/United States Department of Agriculture multiresidue methodology 

5442 would detect and identify the antimicrobial and its residues of concern, as part of 

5443 programs to monitor pesticides in the U.S. food supply. 

5444 12. Data are required if an antimicrobial may be applied directly to water 

5445 or if there is the potential that the antimicrobial-treated water could be used 

5446 directly for drinking water purposes by humans or animals or that contaminated 

5447 water could run-off, leach, or be discharged from treated sites or materials and 

5448 make its way into potable water. 

5449 13. Data are required if an antimicrobial may be applied directly to water 

5450 inhabited by fish or that will be inhabited by fish or if contaminated water could 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

5451 run-off, leach, or be discharged from treated sites or materials and make its way 

5452 into bodies of water containing fish that may be used for human consumption. 

5453 14. Data are required if an antimicrobial may be applied directly to water 

5454 used for irrigation of food crops or such that contaminated water could run-off, 

5455 leach, or be discharged from treated sites or materials to make its way into water 

5456 used for irrigation of food crops. 

5457 15. If the antimicrobial may be applied directly to livestock, metabolically5458 active livestock commodities (e.g., eggs), livestock feed or drinking water, or 

5459 livestock premises, or a livestock metabolism study indicates that residues of the 

5460 antimicrobial may result in livestock commodities, studies are required to 

5461 determine the magnitude of the residues of concern in fat, meat, meat by5462 products, milk, poultry, and eggs that may be consumed by humans. These 

5463 studies, however, may not be required in cases where the livestock metabolism 

5464 studies indicate that transfer of pesticide residues of concern to tissues, milk, and 

5465 eggs is not expected to occur at the maximum expected exposure level for the 

5466 animals. 

5467 16. If food crops or raw agricultural commodities of food crops may be 

5468 exposed to an antimicrobial, then residue studies are required to determine the 

5469 magnitude of the residues of concern that may enter the human diet. Such 

5470 exposures include, but are not limited to, postharvest fruit and vegetable 

5471 treatments and application of antimicrobial chemicals to field crops, mushroom 

5472 houses, empty or occupied beehives, or wood used to construct beehives. 

5473 17. Data on the nature and magnitude of residues in processed food or 

5474 feed are required if antimicrobial residues could potentially concentrate on 
*** EO 12866 Draft – Do Not Cite, Quote or Release During Review ***

5475 processing. If so, the establishment of a separate tolerance higher than that in 

5476 the raw agricultural commodity may be required. 

5477 18. Data are required when dietary exposure values at the tolerance level 

5478 or screening-level (high-end) result in estimates of dietary or aggregate risk that 

5479 meet or exceed the Agency’s level of concern. These data may include, but are 

5480 not limited to, washing, cooking, processing, or degradation studies as well as 

5481 market basket surveys for a more realistic residue determination. Protocols must 

5482 be approved by the Agency prior to the initiation of the study. 

5483 PART 161—[AMENDED] 

5484 7. The authority citation for part 161 continues to read as follows: 

5485 Authority: 7 U.S.C. 136 – 136y. 

5486 Part 161 [Removed] 

5487 8. Remove part 161 is removed:.

5488 ##