*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 1 of 19 EO12866_NanoPests_FRN_DRAFT_2010-07-14.doc 1

EO 12866 Review Draft as submitted. 2

ENVIRONMENTAL PRO TECTION AGENCY 3

[EPA–HQ–OPP–2010-0197; FRL– XXXX

– X ] 4

Pesticides; Policies Concerning Products Contai ning Nanoscale Materials; Opportunity for 5
Public Comment 6

AGENCY: Environmental Protection Agency (EPA). 7

ACTION: Notice

. 8

SUMMARY: This document describes both an interpretation of a st atutory requirement and a 9 separate policy pertaining to pesticide products that contain a “nanos cale material.” In 10 connection with the interpreta tion and policy discussed in th is document, EPA is defining 11
“nanoscale material” as an active or inert ingredient and any component parts thereof 12 intentionally produced to have at least one dimension that me asures between approximately 1 13 and 100 nanometers. As explaine d more fully in this document, EPA believes that information 14 regarding the presence of a nanoscal e material in a registered pe sticide product and its potential 15
effects on humans or the environment is re portable under section 6(a)(2) of the Federal 16 Insecticide, Fungicide, and Roden ticide Act (FIFRA). Such information must also be included, 17 pursuant to 40 CFR 152.50(f)(3), with any applica tion for registration of a pesticide product that 18 contains any nanoscale material. In addition, this document pr oposes a new approach for how 19 EPA will determine on a case-by-case basis whether a nanoscale active or inert ingredient is a 20 “new” active or inert ingredient for purposes of FIFRA and the Pesticide Registration 21 Improvement Act (PRIA), even when an identical, non-nanoscale form of the nanoscale 22 ingredient is already registere d. Notwithstanding the fact that this document is announcing an 23 interpretive rule of general applicability and a separate statement of general policy, both of 24 which are exempt from the notice and comment requirements of the Admi nistrative Procedure 25 Act, EPA is soliciting public comment on the clarity of the reporting requirem ent as it pertains to 26 the presence of nanoscale material s in pesticide products. EPA is also asking for specific input 27 on the proposed policy for determining whether a nanoscale material is “new” under FIFRA and 28

PRIA. 29

30
DATES: Comments must be re ceived on or before [45] days after the date of publication in the 31 Federal Register

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ADDRESSES: Submit your comments, identified by doc ket identification (ID) number EPA– 33 HQ–OPP–2010–0197, by one of the following methods: 34

• Federal eRulemaking Portal : http://www.regulations.gov . Follow the on-line 35 instructions for submitting comments. 36

• Mail : Office of Pesticide Programs (OPP) Regulatory Public Docket (7502P), 37 Environmental Protection Ag ency, 1200 Pennsylvania Ave ., NW., Washington, DC 20460–0001. 38*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 2 of 19 • Delivery : OPP Regulatory Public Do cket (7502P), Environmental Protection Agency, 39 Rm. S–4400, One Potomac Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, VA. Deliveries 40 are only accepted during the Docket Facility’s no rmal hours of operation (8:30 a.m. to 4 p.m., 41 Monday through Friday, excluding legal holidays) . Special arrangements should be made for 42 deliveries of boxed information. The Docket Facility telephone number is (703) 305–5805. 43

Instructions : Direct your comments to docke t ID number EP A–HQ–OPP–2010-0197. 44 EPA's policy is that all comments received will be included in the docket without change and 45 may be made available on-line at http://www.regulations.gov , including any personal 46 information provided, unless the comment include s information claimed to be Confidential 47 Business Information (CBI) or other information whos e disclosure is restrict ed by statute. Do not 48 submit information that you consider to be CBI or otherwise protec ted through regulations.gov 49 or e-mail. The regulations.gov website is an “anonymous access” system, which means EPA 50 will not know your identity or contact inform ation unless you provide it in the body of your 51 comment. If you send an e-mail comment directly to EPA without going through 52 regulations.gov, your e-mail address will be automati cally captured and included as part of the 53 comment that is placed in the docket and made available on the Internet. If you submit an 54 electronic comment, EPA recomme nds that you include your name and other contact information 55 in the body of your comment and with any disk or CD-ROM you submit. If EPA cannot read 56 your comment due to technical difficulties and cannot contact you for clarification, EPA may not 57 be able to consider your comment . Electronic files should avoid the use of special characters, 58 any form of encryption, and be fr ee of any defects or viruses. 59

Docket : All documents in the docket are list ed in the docket index available at 60 http://www.regulations.gov . Although listed in the index, so me information is not publicly 61 available, e.g., CBI or other information whose disc losure is restricted by statute. Certain other 62 material, such as copyrighted material, is not pl aced on the Internet and will be publicly available 63 only in hard copy form. Publicly available docket materials are ava ilable either in the electronic 64
docket at http://www.regulations.gov , or, if only available in ha rd copy, at the OPP Regulatory 65 Public Docket in Rm. S–4400, One Potomac Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, 66 VA. The hours of operation of this Docket Facil ity are from 8:30 a.m. to 4 p.m., Monday through 67 Friday, excluding legal holidays. The Docket Facility telephone number is (703) 305–5805. 68

69
FOR FURTHER INFORMATION CONTACT: Demson Fuller, Antimicrobials Division 70 (7510P), Office of Pesticide Programs, Envi ronmental Protection Agency, 1200 Pennsylvania 71 Ave., NW., Washington, DC 20460–0001; teleph one number: 703-308-8062; fax number: 703- 72 308-8005; e-mail address: fuller.demson @epa.gov

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74
SUPPLEMENTARY INFORMATION: 75

I. General Information 76

A. Does this Action Apply to Me? 77

This action is directed to those persons who manufacture, distri bute, sell, apply, or 78 regulate pesticide products, includi ng agricultural, commercial, a nd residential products (NAICS 79 codes 32532 and 32561). This listing is not intended to be exhaustive, but rather provides a 80*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 3 of 19 guide for readers regarding entities likely to be affected by this act ion. Other types of entities not 81
listed in this Unit could also be affected. The North American Industrial Classification System 82 (NAICS) codes have been provide d to assist you and others in determining whether this action 83 might apply to certain entities. If you have any questions regard ing the applicability of this 84 action to a particular entity, consult the person listed under FOR FURTHER INFORMATION 85

CONTACT. 86

B. What Should I Consider as I Prepare My Comments for EPA? 87

1. Submitting CBI . Do not submit this information to EPA through regulations.gov or e88 mail. Clearly mark the part or all of the information that you claim to be CBI. For CBI 89 information in a disk or CD-ROM that you mail to EPA, mark the outside of the disk or CD90 ROM as CBI and then identify electronically within the disk or CD-ROM the specific 91
information that is claimed as CBI. In addition to one complete version of the comment that 92 includes information claimed as CBI, a copy of the comment that does not contain the 93 information claimed as CBI must be submitted for inclusion in the public docket. Information so 94 marked will not be disclosed except in accordance with procedures set forth in 40 CFR part 2. 95

2. Tips for preparing your comments . When submitting comments, remember to: 96

97 i. Identify the document by docket ID number and other identifying information (subject 98 heading, Federal Register date and page number). 99

ii. Follow directions. The Agency may ask you to respond to specific questions or 100 organize comments by referencing a Code of Federal Regulations (CFR) part or section number. 101

iii. Explain why you agree or disagree; suggest alternatives and substitute language for 102 your requested changes. 103

iv. Describe any assumptions and provide a ny technical information and/or data that you 104
used. 105

v. If you estimate potential costs or burdens, explain how you arrived at your estimate in 106 sufficient detail to allow for it to be reproduced. 107

vi. Provide specific examples to illustra te your concerns and suggest alternatives. 108

vii. Explain your views as cl early as possible, avoiding the use of profanity or personal 109
threats. 110

viii. Make sure to submit your comments by the comment period deadline identified. 111

112

II. Applicable Statutory and Regulatory Requirements 113

As a general matter, pesticides may not be sold or distributed in the United States unless 114 they are registered with the EPA. FIFRA secti on 3(a) (7 U.S.C. 136a(a)). In order to obtain a 115 pesticide registration, an app licant must provide EPA with data (or cite existing data) 116 demonstrating that the proposed registration co mplies with the requirement for registration. 117*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 4 of 19 FIFRA section 3(c)(1)(F) (7 U.S.C. 136a(c)(1)(F)) . FIFRA contains two provisions under which 118 EPA may register pesticides: se ction 3(c)(5) for “unconditional” registration and section 3(c)(7) 119 for “conditional” registration (7 U.S.C. 136a(c)(5 ) and 7 U.S.C. 136a(c)(7)). Importantly, EPA 120 must make statutorily required findings for each and every pesticide product for which 121 registration is sought, regardless of whether another pesticide pr oduct with the same or similar 122 composition and use patterns is already registered. 123

124 The standard for determining whether an app lication should be granted unconditionally is 125 found in FIFRA section 3(c)(5). This section provides that, in order to grant a registration, EPA 126 must find that a product’s com position warrants the proposed claims for it; that the product’s 127 labeling and other material required to be subm itted comply with FIFRA; that the product will 128 perform its intended function without causing un reasonable adverse effects on the environment; 129 and that, when used in accordance with wide spread and commonly recognized practice, the 130 product will not cause unreasonable adve rse effects on the environment. 131

132
FIFRA defines “unreasonable adverse effect s on the environment” as including “any 133 unreasonable risk to man or the environment, taking into account the economic, social, and 134
environmental costs and benefits of the use of any pesticide.” FIFRA section 2(bb) (7 U.S.C. 135 136(bb)). Thus, a critical aspect of determin ing whether or not a pe sticide product should be 136 granted a registration is an eval uation of whether the benefits associated with the use of a 137 pesticide exceed the risks associated with such use. The burden of demo nstrating that a product 138 meets the standards for registration rests at all times on the registrant or app licant for registration. 139 See, e.g. Industrial Union Dept. v. American Petroleum Institute, 448 U.S. 607, 653 n. 61 (1980); 140 Environmental Defense Fund v. EPA, 510 F.2d 1292, 1297, 1302 (D.C. Cir. 1975). 141

142 If an applicant cannot provide necessary da ta for EPA to make the determinations 143 required to register a product unconditionally und er FIFRA section 3(c)(5), EPA may still be 144 able to register the product “conditionally” under FIFRA section 3(c)(7). FIFRA section 3(c)(7) 145 authorizes EPA to register a pesticide product on th e condition that the applicant provides 146 additional data necessary to s upport a finding that the product meet s the statutory standards in 147 FIFRA section 3(c)(5). FIFRA section 3(c)(7 ) authorizes conditional registration in three 148 circumstances. First, the Agency may condition ally register a product if EPA determines, among 149 other things, that the product is identical or substantially similar to a currently registered 150 pesticide or differs only in wa ys that would not significantly increase the risk of unreasonable 151 adverse effects on the environment, and that approving the registration in the manner proposed 152 would not significantly increase the risk of any unreasonable adverse effect on the environment. 153 FIFRA section 3(c)(7)(A) (7 U.S.C. 136a(c)(7)(A)) . Products approved unde r this authority are 154 commonly called “me-too registratio ns.” Second, EPA may register a pesticide for an additional 155 use, if the applicant provides da ta to evaluate the safety of the new use, and use of the product 156 would not significantly increase the risk of unr easonable adverse effects on the environment 157 compared to products already registered. FIFR A section 3(c)(7)(B) (7 U.S.C. 136a(c)(7)(B)). 158 These product approvals are referred to as “new use” registrations. Finally, EPA may 159 conditionally register a pesticide product that contains an active ingredient not present in any 160 currently registered pesticide product, if the Administrato r determines that: 161

162*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 5 of 19 1. The applicant has provided all data necessa ry to evaluate the safety of the pesticide, 163 with the exception of any data which are lack ing because the applican t has not had enough time 164 to generate the data since learning of the requirement; 165

166 2. Use of the pesticide during the time peri od needed to develop the additional data will 167
not cause unreasonable adverse e ffects on the environment; and 168
169 3. Use of the pesticide is in the public in terest. FIFRA section 3(c)(7)(C) (7 U.S.C. 170 136a(c)(7)(C)). 171

172 As with applications for unconditional re gistrations, applicants for conditional 173 registration bear the burde n at all times of demons trating that the statutor y standards are met. 174

175 The Agency’s interest in data to evaluate the risks and benefits of a pesticide does not 176 necessarily end once EPA has registered a pestic ide product. Accordingly, other provisions of 177 FIFRA allow the Agency to require pesticide re gistrants to develop a nd submit information the 178 Agency believes it needs in order to maintain the registration of pestic ide products. In addition, 179 FIFRA section 6(a)(2) provides th at registrants must inform th e Agency of certain relevant 180 information relating to their pr oducts, even though it was not sp ecifically requested by EPA. 181 Specifically, FIFRA section 6(a)(2 ) requires that, “[i]f at any tim e after the registration of a 182 pesticide the registrant has addi tional factual information regard ing unreasonable adverse effects 183 on the environment of the pesticide, the regist rant shall submit such information to the 184 Administrator.” (7 U.S.C. 136d(a)(2)). 185

186 In 1997, EPA promulgated a final rule at 40 CFR part 159, subpart D in the Federal 187 Register issue of September 19, 1997 (62 FR 49370)(FRL-5739-1), setting forth EPA’s 188 interpretation and enforcement policy regarding FIFRA section 6(a)(2). The rule explains, 189 among other things, what information EPA regards as “additional” and “factual,” as well as how 190 quickly and to whom such information must be reported. 191
192 The regulation specifies many kinds of inform ation, from varied sc ientific disciplines, 193 that EPA requires registrants to submit pursuan t to FIFRA section 6(a)(2). The types of 194 information reflect the variety of scientific data used by EPA in making the statutorily required 195 determinations – whether pesticides cause unrea sonable adverse effects on the environment. 196 Thus, for example, the regulations generally requir e registrants to report st udies indicating that a 197 pesticide causes new or a higher incidence of to xic effects than previously identified (see 40 198 CFR 159.165) and to report incident s involving injury to humans, pets or wildlife resulting from 199 exposure to a pesticide (40 CFR 159.184). But, EP A uses other types of information that do not 200 directly demonstrate adverse effects in its risk assessments, and new factual information of this 201 kind is also reportable under the regulation. For example, registra nts must report studies that 202 identify new metabolites, degradates, impurities, or contaminants of pesticides (40 CFR 203 159.179); certain information on the de tection of pesticide residues in water, food, and feed (40 204 CFR 159.178); and new studies of human e xposure (40 CFR 159.170). In sum, EPA’s 205 regulation requires reporting of ma ny types of information relevant to EPA’s assessment of the 206 safety of a pesticide product – in the word s of section 6(a)(2) “information regarding 207
unreasonable adverse effects on the environment of the pesticide” – not merely information that 208 directly concerns adverse effects. 209*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 6 of 19 210 In promulgating that regulation, however, EPA also recognized it was impossible to 211 establish rules addressing every type of factual information that might become relevant in the 212 future to judging whether a registered pesticid e product continued to meet the FIFRA statutory 213 standards. Accordingly, 40 CFR 159.195(c) provides: 214

215 “The registrant shall submit to the Administra tor information other than that described in 216 §§159.165 through 159.188 if the registrant knows, or reasonably should know, that if the 217 information should prove to be correct, EPA might regard the information alone or in 218 conjunction with other informa tion about the pesticide as raising concerns about the 219 continued registration of a product or about the appropriate terms and conditions of 220 registration of a product.” 221

222 In addition, 40 CFR 159.195( c) provides that: 223

224 “[t]he registrant shall su bmit . . . information other than that described in §§159.165 225 through 159.188 if the registrant has been informed by EPA that such additional 226 information has the potential to raise ques tions about the conti nued registration of a 227 product or about the appropriate terms and conditions of regist ration of a product.” 228
229 In light of the preceding, it must be emphasized that EPA is not expanding its 230 interpretation of FIFRA section 6(a)(2) or ch anging its regulations through this document. 231 Rather, consistent with EPA’s section 6(a)(2) regulations, EPA is merely identifying a set of 232 information, to which the FIFRA section 6(a)(2) reporting requirement alr eady applies, that is 233 broader than the subset of reporta ble section 6(a)(2) data explicit ly identified at present under the 234 section 6(a)(2) regulations. 235

236 Further, the Agency notes that the identif ication of information as reportable under 237 FIFRA section 6(a)(2) does not necessarily mean that any particular pesticide or group of 238 pesticides, to which such information pertains, poses a risk. Rather, the requirement merely 239
indicates that EPA has determined that a particular type of info rmation is relevant to, and may 240 improve the Agency’s ability to assess, the safety of a pesticide. 241

242 Finally, EPA promulgated a regulation in th e Federal Register of May 4, 1988 (53 FR 243 15952)(FRL-3266-96) concerning the s ubmission of applications for registration at 40 CFR part 244 152. That rule specifies, among other things, certai n types of information that an application for 245 registration of a pestic ide product must contain. The rule provides that the applicant must 246 “furnish with his application any factual in formation of which he is aware regarding 247 unreasonable adverse effects of the pesticide on man or the environment, which would be 248 required to be reported under FIFRA section 6(a)(2 ), if the product were registered.” (40 CFR 249 152.50(f)(3). 250

251 Registrants’ compliance with section 6(a )(2) and EPA’s implementing regulations in 252
Parts 152 and 159 ensures that EPA has access to a ny additional factual information that could 253 be important for determining whether a previous Agency decision to register a pesticide remains 254 a correct one, and whether a registered pesticide can in fact be used without posing unreasonable 255
adverse effects to human health and the environm ent. This provision of FIFRA recognizes that 256*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 7 of 19 registrants may come into the possession of impor tant new information that was not anticipated 257 by the Agency or of information the importance of which was not previously known, and that in 258 the absence of registrants submitting such info rmation, EPA might well remain unaware of the 259 information. Thus, section 6(a)(2) and Part 159 serve to provide an important ongoing check on 260 the correctness of the original decision to regi ster a pesticide. Failures to report required 261 information, or delays in reporting, are regarded by EPA as violations of FIFRA section 6(a)(2), 262
which in turn makes them actionable under FIFR A sections 12(a)(2)(B)( ii) and 12(a)(2)(N) (7 263 U.S.C. 136j(a)(2)(B)(ii) a nd 7 U.S.C. 136j(a)(2)(N)). 264

265

III. EPA’s Interest in Nanoscale Ma terials as Pesticide Ingredients 266

A. Applicable Definition of “Nanoscale Material” 267

268 With FIFRA section 6(a)(2) as a backdrop, the focus of this document turns next to the 269 topics of nanotechnology and the presence of nanoscale materials as either active ingredients or 270 inert ingredients in pesticide products. At th e outset, it is important to clarify some key 271 terminology that is being used for purposes of this document. 272

273 To date, EPA has not develope d formal definitions for the terms “nanotechnology” or 274 “nanoscale materials” or any similar te rms for regulatory purposes under any statute 275 administered by the Agency. Broad definitio ns and discussions of nanotechnology generally 276 reflect the same common elements, namely: 277

278 1. The material’s particle size measures typically between approximately 1 and 100 279 nanometers in at least one dimension; 280

281 2. The material exhibits unique or novel prope rties compared to larger particles of the 282 same material; and 283

284 3. Rather than occurring naturally, the materi al has been manufactured or engineered to 285 take advantage of these unique properties. See, for example, the definition from the National 286 Nanotechnology Initiative at: http://www.nano.gov/htm l/facts/whatIsNano.html

. 287

288 These elements do not readily work for a regulatory definition because of the high degree 289 of subjectivity involved with interpreting such phrases as “unique or novel properties” or 290 “manufactured or engineered to take advantage of these properties.” Mo reover, the contribution 291 of these subjective elements to risk has not been established. 292
293 Instead, OPP will focus on more objective criteria in its definition of “nanoscale material.” 294
In connection with the interpretation and policy discussed in this document, OPP defines 295
“nanoscale material” as an active or inert ingredient and any component parts thereof 296 intentionally produced to have at least one dimension that me asures between approximately 1 297 and 100 nanometers. In determining whether an ingredient meets this definition, EPA will 298 review, among other things, the manufacturing process to determine whether it employs 299 processes to create or enhance the proportion of nanoscale material s in the product, as compared 300 with other processes used to produce similar products. 301*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 8 of 19 302 B. Potential of Nanoscale Materials to Affe ct Human Health and the Environment Adversely 303

304 There is a growing body of scientific evid ence showing that differences can exist 305 between nanoscale material(s) and thei r non-nanoscale counterpart(s) (Ref. 14 ) . Nanoscale 306 materials may have different or enhanced pr operties – for example, electrical, chemical, 307 magnetic, mechanical, thermal, or optical properties – or features, such as improved hardness or 308 strength, that are highly desirable for applications in commercial, medical, military, and 309 environmental sectors (Ref. 13). These properties are a direct c onsequence of small size, which 310 results in a larger surface area per unit of vol ume and/or quantum effects that occur at the 311 nanometer scale (i.e., 1 x 10 -9 meters). Small size itself is al so a desirable property of nanoscale 312 materials that is exploited for miniaturization of applications/p rocesses and/or stabilization or 313 delivery of payloads to diverse environmen ts or incorporation into diverse products. 314
315 A number of organizations have considered whether the small size of nanoscale materials or 316 the unique or enhanced properties of nanoscale ma terials may, under specific conditions, pose new or 317

increased hazards to humans and the environment . Government, academic, and private sector 318 scientists in multiple countries are performing res earch into the human health effects of diverse 319 nanoscale materials, resulting in a substantial and rapidly growi ng body of scientific evidence. 320 These research findings point ge nerally to the possibility for nanoscale materials to adversely 321
affect human health and the environment. Re search also indicates, however, that not all 322
materials in the nanoscale size ra nge behave differently from larg er sized materials of the same 323 substance. Recently, governmental and expert peer review organizations have reviewed and 324
summarized this evidence and offered views ab out the implications of this evidence for 325 environmental and human health and safety. 326

327 For instance, in 2009, t he National Institute of Occupati onal Safety and Health (NIOSH) 328 issued a report, “Approach es to Safe Nanotechnology: Managing the Health and Safety Concerns 329 Associated with Engi neered Nanomaterials,” which summarized the available scientific 330
information about nanoscale materials and identifi ed the following potentia l health and safety 331 properties: 332

333

 “Nanomaterials have the greatest potential to enter the body through the respiratory sys334 tem if they are airborne and in the form of respirable-sized particles (nanoparticles). They 335 may also come into contact with the skin or be ingested.” 336

337

 “Based on results from human and animal st udies, airborne nanopart icles can be inhaled 338 and deposit in the respiratory tract; and ba sed on animal studies, nanoparticles can enter 339 the blood stream, and translocate to other organs.” 340

341

 “Experimental studies in rats have shown that equivalent mass doses of insoluble 342 incidental nanoparticles are more potent than large particles of similar composition in 343 causing pulmonary inflammation and lung tumo rs. Results from in vitro cell culture 344 studies with similar materials are genera lly supportive of the biological responses 345
observed in animals.” 346

347*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 9 of 19  “Experimental studies in animals, cell cultu res, and cell-free systems have shown that 348 changes in the chemical composition, crystal st ructure, and size of particles can influence 349 their oxidant generation prope rties and cytotoxicity.” 350

351

 “Studies in workers exposed to aerosols of some manufactured or incidental microscopic 352 (fine) and nanoscale (ultrafine) particles ha ve reported adverse lung effects including 353 lung function decrements and obstructive and fi brotic lung diseases. The implications of 354 these studies to engineered nanoparticles, wh ich may have different particle properties, 355
are uncertain.” 356

357

 “Some nanomaterials may initiate catalytic reactions depending on their composition and 358
structure that would not othe rwise be anticipated based on their chemical composition.” 359

360 (Ref. 2). 361

362 Earlier the same year, the Scientific Committee on Emerging and Newly Identified 363 Health Risks (SCENIHR), an independent scientific committee advising the European 364
Commission’s Health and Consumer Directorate, issued a report , “Risk assessment of products 365 of nanotechnologies.” The SCENIH R report identified properties similar to those identified in 366 the NIOSH report: 367

368 “Some specific hazards, discussed in the cont ext of risk for human health, have been 369 identified. These include the possibility of some nanoparticles to induce protein 370 fibrillation, the possible pathological e ffects caused by specific types of carbon 371 nanotubes, the induction of genot oxicity, and size effects in terms of biodistribution.” 372

373
and: 374

375 “For some nanomaterials, toxic effects on environmental organisms have been 376 demonstrated, as well as the potential to transfer across environmental species, 377 indicating a potential for bioaccu mulation in species at the en d of that part of the food 378
chain.” 379

380 (Ref. 17). 381

382
In another recent surv ey of scientific research on nanoscale materials, the authors 383 reported: 384

385 “Many studies have examined the pro-infl ammatory effects of manufactured NPs 386 [nanoparticles], on the basis that their ability to cause infl ammation is a major predictor 387 of potential hazard in such pa rticles. The first important finding was that NPs have a 388 more pronounced effect on inflammation, cell damage and cell stimulation than an 389 equal mass of particles of the same material of greater size [(Ref. 3)]. This appears to 390
hold true for materials as varied as carbon black, titanium dioxide, various metals and 391 polystyrene [(Ref. 5)]. Surface area is the metric driving the pro-inflammatory effects 392
and this is evident both in vitro [(Ref. 4)] and in vivo [(Ref. 5)], particles of various 393 sizes producing inflammatory effects that are di rectly related to the surface area dose.” 394*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 10 of 19 395 (Ref. 18). 396
397 Other reports in the scientific literature ha ve indicated that some nanoscale materials may 398 cross the placental barrie r (Ref. 20) or translocate to diverse organs following oral exposure (Ref. 399 10). Once in these diverse sites and organs, th e large surface area of nanoscale materials may 400 facilitate increased reactivity and/or an inflam matory response, resulting in toxic effects. 401

402 Two recent literature surveys describe a br oad range of effects in non-mammalian species 403 following exposure to nanoscale materials (Ref s. 8 and 11). These include, for example, 404 increased ventilation rates, mucu s production, and pathologies, a nd related alteration of enzyme 405
activities and indicato rs of oxidative stress in rainbow trout, Oncorhyncus mykiss (Refs. 6 and 406 19), and ingestion and accumulation of nanoscale ma terial in the digestive tract, as well as 407 mortality, increased heart rate s, and reduced fecundity in Daphnia magna (Refs. 12, 15, and 16). 408 Translocation of nano-scale materials from gill and gut surface to blood and other organs in 409 exposed Medaka, Oryzius latipes , has also been reported (R ef. 9) and carbon nanotubes, 410 although unable to cross the egg surface, have been shown to delay hatching in zebrafish, Danio 411

rerio (Ref. 1). 412

413 While the reports and articles cited above ha ve focused primarily on differences between 414 nanoscale material and conventionally sized mate rial of the same substances, EPA has also 415 consulted with the FIFRA Scientific Advisory Pane l (SAP) on the extent to which different types 416 of nanoscale materials may displa y different properties. (The SAP is a federal advisory 417 committee consisting of external, independent, ex pert, scientific peer reviewers who provide 418
advice to EPA on scientific issues involved in the regulati on of pesticides.) In response to EPA 419 questions on how size and other pr operties of nanoscale materials potentially affect risk and how 420 to assess such risks, the SAP said: “Existi ng data clearly indicate that many properties of 421 particles change with size , including rate of release of ionic fo rms of metal, reactivity or catalytic 422 efficiency, Plasmon resonance, and quantum effects. . . . The effect of pa rticle size on biological 423 responses to particle exposure is less well defined.” (Ref. 7). Th e SAP also noted that “[o]ther 424 physicochemical properties, such as shape, charge and surface coating, are also likely to impact 425 biological response and environmen tal fate [of nanoscale materials]. . . . The lack of a clear 426 understanding of how part icle size and other physi cal properties affect ha zard profiles led most 427 Panel members to be unsupportive of bridging among silver-based materials with different 428 properties.” (Ref. 7). 429

430 It is important to emphasize that, while the conclusions described above apply generally 431
to the class of nanoscale material s, an individual type of nanom aterial may not display all or 432 even any of the characteristics observed and repo rted for other nanoscale materials. In other 433 words, some nanoscale materials may have proper ties which, for purposes of assessing the risk 434 of a pesticide, are essentially identical to larger sized materials of the same substance. So, it 435 appears increasingly likely that there are few, if any, universal “nanoscale” effects, and the 436
distinctive effects seen at nanos cale are specific to the propert ies of each material type under 437 specific exposure scenarios. Thus, EPA does not regard the fact that an ingredient meets our 438
definition of a nanoscale material as evidence th at a pesticide containing the ingredient no longer 439 meets the statutory standards for registration. Ra ther, the presence of a nanoscale material in a 440*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 11 of 19 pesticide is grounds for EPA to c onsider the possible need for data to characterize the potential 441 of the ingredient to pose risks. 442

443 Finally, scientifically speaking, there currently is no bright li ne with respect to a size 444 below (or above) which nanoscale materials do (or do not) exhibit properties that might raise risk 445 concerns. Therefore, the precise size range in nanometers addresse d by the policies announced 446 in this document are subject to change in the future as new information becomes available. 447

448
C. Nanoscale Materials and Pesticides 449
450 The Agency has information indicating that the use of nanotechnology has started to 451 expand into pesticide products, as it already has in many other fields . For instance, a number of 452 companies have contacted EPA expressing an inte rest in obtaining regist rations for pesticide 453 products containing ingredients identified as na nosilver or nanosilver composite structures 454 (jointly referred to as “nanosilver”) and several companies have submitted applications to 455 register pesticides containing nanosilver. In addition, EPA now has information suggesting that 456 there are other pesticide products currently re gistered and in the marketplace that contain 457 nanosilver as an active ingredient. 458
459 As already summarized above, in order for EP A to fulfill its responsibilities to regulate 460 pesticides under FIFRA, EPA needs to determin e whether pesticidal products containing an 461 intentionally-produced nanoscale material, whether as an active or inert ingredient, meet the 462 statutory standards for regist ration. Accordingly, EPA need s not only to know about the 463 presence of nanoscale materials in pesticide products, but also to have available all information 464 relevant to the assessment of the potential of such pesticide products to cause unreasonable 465 adverse effects on the environment, and/or to determine whether EPA should continue the 466 registration of a product, or ame nd, as appropriate, the terms and conditions of registration of a 467 product. 468
469

IV. Reporting the Presence of Nanoscale Materials in Pesticide Products 470

As mentioned above, FIFRA section 6(a)(2 ) and implementing regulations in 40 CFR 471 part 159 require pesticide regist rants to report certain informa tion if that information: 472

473 1) Is additional; 474

475 2) Is factual; and 476

477 3) Regards unreasonable adverse effects on the environment of the pesticide. Per 40 478 CFR 159.195, this includes information that, if co rrect, a registrant knows, or reasonably should 479 know, would be regarded by EPA, either alone or in conjunction with other information about 480 the pesticide, as raising concerns about the continued registration of a product or about the 481 appropriate terms and conditions of registration of a product. 482

483 Under EPA’s section 6(a)(2) re gulations, which are codified at 40 CFR Part 159, Subpart 484 D, once the Agency has informed registrants that EPA considers a particular type of information 485*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 12 of 19 relevant to determining whether a pesticide ha s the potential to cause unreasonable adverse 486 effects on the environment, that type of info rmation becomes reportable under FIFRA section 487 6(a)(2). The failure to report required information, or delays in reporting, are regarded by EPA 488 as violations of FIFRA section 6(a)(2), which in turn makes them subject to enforcement action 489 under FIFRA sections 12(a)(2)(B)(ii) and 12(a)(2)(N ) (7 U.S.C. 136j(a)(2)(B)(ii) and 7 U.S.C. 490 136j(a)(2)(N). 491
492 In light of the foregoing and in consideration of the potenti al for nanoscale material to 493 cause different effects and to behave differently in the environment and within organisms from 494 larger particles of the same substance, as well as from nanoscale ma terials with different 495 characteristics (see Unit III. B.), it is EPA’ s position that any of the following types of 496 information are relevant to assessing the poten tial of a pesticide to cause unreasonable adverse 497
effects on the environment and are thus reportable under FIFRA section 6(a)(2): 498
499

 any information concerning or indicating the presence of nanoscale material, whether as 500 an active ingredient or as an inert ingredient; 501

502

 for any pesticide product that contains nanos cale material, whether active or inert, any 503 existing information not previously provided to the Agency that characterizes the size and 504
size distribution of the nanoscale mate rial as measured in nanometers; 505

506

 for any pesticide product that contains nanoscal e materials, whether active or inert, any 507 existing information not previously provi ded to the Agency that describes the 508 manufacturing process used to produce the nano scale material in whatever size range it is 509 produced; 510

511

 for any pesticide product that contains nanoscal e materials, whether active or inert, and 512 that also is or will be used for an end-use formulation that contain(s) a composite (e.g., 513 the active ingredient is a matrix complex comprised of the nanoscale material(s) in 514 combination with a carrier, su ch as silica or sulfur), any existing information not 515 previously provided to the Agency that char acterizes the size and si ze distribution of the 516 composite; and 517

518

 for any pesticide product that contains nanoscal e materials, whether active or inert, any 519 existing information not previously provided to the Agency that shows adverse effects at 520 any level of exposure to the nanoscale materi al on humans or nont arget species, and/or 521 that shows the levels or nature (e.g. routes, frequency, or life stage) of potential human 522 and environmental exposure. 523

524 Importantly, the foregoing is not intended to be an exclusive list. To the extent that a 525 registrant has a pesticide product that contains a nanoscale material , and in addition has any other 526 existing information not captured in the list above th at pertains to, concerns , or otherwise relates 527
to the nanoscale material and ha s the potential to rais e questions about the continued registration 528 of a product or the appropriate terms and conditi ons of a product registration, it is EPA’s position 529 that it too must be submitted to the Ag ency under FIFRA section 6(a)(2). 530

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Page 13 of 19 In addition, since the types of informati on described above are reportable under FIFRA 532 section 6(a)(2), these types of information also are reportable in connectio n with any application 533 to register a pesticide product containing any na noscale material (40 CFR 152.50(f)(3)). As with 534 the reporting obligation under FIFRA section 6(a)(2), EPA woul d consider the failure to provide 535 these types of information with an application for a product containing nanoscale material to be a 536 violation of FIFRA sections 12( a)(2)(B)(ii) and 12(a)(2)(N). 537

538 Agency regulations implementing FIFRA sectio n 6(a)(2) provide that a registrant must 539 submit information to EPA that is reportable under section 6(a)(2) no later than the 30 th calendar 540 day after the registrant first possesses or beco mes aware of the information (40 CFR 159.155). 541 In addition, a registrant is required to subm it to EPA any section 6(a)(2) information not 542 explicitly covered under the section 6(a)(2) regu lations if EPA has informed the registrant that 543
such additional information has th e potential to raise questions about the continued registration 544 of a product or the appropriate terms and c onditions of registration of a product (40 CFR 545 159.195). The Agency will begin to apply the inte rpretation announced herein that pertains to 546 nanoscale materials and FIFRA section 6(a)(2) 90 days after publication of this document. 547 Absent specific, earlier notice to a registrant, ther efore, EPA will view that date as the date on 548 which a registrant first became aware that such information is reportable under section 6(a)(2). 549 Thus, absent a specific notice, a registrant will co mply with its FIFRA section 6(a)(2) obligations 550 in this area as long as EPA receives the reportabl e information within 120 days after publication 551
of this document. 552

553 Finally, although this announcemen t currently limits this re porting requirement only to 554
nanoscale materials that are “int entionally produced” such that a ny dimension falls within the 555 specific size range currently under scrutiny (i.e ., between approximately 1 and 100 nanometers), 556 it is subject to change in the future as new info rmation becomes available that warrants change. 557 Accordingly, the Agency reserves the right to revisit and change the reporting requirement 558 announced herein if necessary. 559

560

V. Proposed Policy Regarding Classificati on of Applications under FIFRA and PRIA 561 for Products Containing Nanoscal e Active and Inert Ingredients 562

Through this document, EPA also is more broadly announcing how it proposes to address 563
the status of nanoscale materials as new active or inert ingredients fo r purposes of both FIFRA 564 and PRIA. As discussed in more detail above, u nder FIFRA, all pesticides must meet stringent 565 statutory and regulatory st andards before they are registered by the Agency and allowed to be 566 marketed and sold. Pesticides containing nanos cale materials, whether as active or inert 567 ingredients, must meet the same safety standard s as other pesticides. Because of the large and 568 increasing body of data described in Unit III B. of this document demonstrating that size can 569 alter the manner in which materials behave and, in turn, the potential risk to human health and 570 the environment associated such materials, EPA proposes to apply an initial presumption that 571 active and inert ingredients, wh ich are the nanoscale versions of non-nanoscale active and inert 572 ingredients already presen t in registered pestic ide products, are potentiall y different from those 573 conventionally-sized counterparts. For the same reasons, EPA also proposes to apply an initial 574 presumption that nanoscale active and inert ingredients are potentially differe nt even from other, 575*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 14 of 19 already-registered nanoscale versions of the same ingredients. As explained below, however, 576 applicants can overcome this presum ption on a case-by-case basis. 577

578 Historically, EPA has evaluated an applicati on for registration of a pesticide product that 579 claims to have the same composition and uses as a currently registered pesticide – a so-called 580 “me-too” application – under either the “conditio nal” registration or “unconditional” registration 581 authorities in FIFRA section 3(c )(7) and section 3(c)(5), respec tively. In making the statutory 582 determinations under section 3(c )(7)(A) – whether the applican t’s product is identical or 583 substantially similar to a currently registered pe sticide or differs only in ways that would not 584 significantly increase the risk of unreasonable adverse effects on the environment, and that 585 approving the registration in the manner proposed w ould not significantly increase the risk of 586 any unreasonable adverse effect on the environment – EPA has focused on whether the use 587 patterns of the products are iden tical or similar and whether th e ingredients present in the 588 products have the same chemical structure and ar e present in about the same percentages. Until 589 recently, EPA generally has not focused on the size of an ingredient as an attribute relevant to 590 making the determinations under se ction 3(c)(7)(A). As noted a bove, however, once the size of 591 an ingredient is reduced below approximat ely 100 nm, a substance can exhibit different 592 properties, and therefore it may also have diffe rent potential environmen tal health and safety 593 properties. Accordingly, for a product containing an ingredient that is a nanoscale version of a 594 conventionally-sized active or iner t ingredient contained in an al ready- registered product, EPA 595 necessarily will require adequate data in order to determine that the nanoscale material differs 596 only in ways that do not signifi cantly increase the risk of unr easonable adverse effects on the 597 environment and that approving th e registration in the manner pr oposed would not significantly 598 increase the risk of any unreas onable adverse effect on the envir onment, and/or require different 599 terms and conditions for the registration. The implic ation of this thinking, therefore, is that EPA 600 cannot automatically make the re quisite findings absent specif ic information on the nanoscale 601 material included in a pesticid e product when the application relies on a comparison to a 602 currently registered pesticide product containing either a non-na noscale version of the same 603 ingredient or another nanoscale ve rsion of the ingredient that ha s different characteristics. The 604 Agency will follow the same thinking in making the statutorily required determinations under 605 FIFRA section 3(c)(7)(B) and 3(c)(7)(C), as well as FIFRA section 3(c)(5). 606

607 For purposes of registration under FIFRA sec tion 3(c)(5) or 3(c)(7), therefore, EPA 608 would initially classify any app lication for registration of a pest icide product containing an active 609 or inert ingredient that is a nanoscale material as an application for a “new” active or inert 610 ingredient, even when another registered pest icide product contains a non-nanoscale form of the 611 ingredient or a nanoscale form of the ingredie nt with different size dimensions or other 612 properties. This initial presumption, however , could be rebutted on a case-by-case basis through 613 the submission of, among other possi bilities, bridging data or othe r information demonstrating to 614
EPA’s satisfaction that the nanoscale material’s properties, which are re levant to assessing the 615 potential risks to human health a nd the environment, are substantia lly similar to the properties of 616 the already-registered non-nanoscale or already-re gistered nanoscale form of the material, or that 617 the nanoscale material differs only in ways that do not significantly increase the risk of 618 unreasonable adverse effects on the environment, and that approving th e registration in the 619 manner proposed would not significa ntly increase the risk of a ny unreasonable adverse effect on 620 the environment. If an app licant can make this showing to EPA’s satisfaction, then the 621 application could be processed as a me-too application within the timeframes prescribed for such 622*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 15 of 19 applications. However, if an applicant cannot make this showing to EPA’s satisfaction, then 623 EPA would process such products as new active ingredients or ne w inert ingredients and would 624 complete its review within the timeframes pr escribed for such applications. In those 625 circumstances, the Agency would likely require the applicant to provide the types of data 626 typically required for an assessment of the potenti al hazards and exposure to a new active or inert 627 ingredient. Under this proposed po licy, it would also follow that if a registrant wished to change 628 the composition of its product to include a na noscale version of a ma terial that EPA had 629 previously approved in non-nanoscale form, the registrant would need to notify EPA and obtain 630 EPA approval before making such a change in the composition of its product. 631

632

VI. Does This Document Contain Binding Re quirements and When Do They Take Effect? 633

This document announces how FIFRA sec tion 6(a)(2) applies in a particular 634 circumstance. This announcement informs regist rants that certain information is reportable 635 pursuant to FIFRA section 6(a )(2) and 40 CFR 159.195. As such, the document explains the 636 applicability of the statute a nd regulation and makes clear the requirement also applies to 637 applicants through 40 CFR 152.50(f)(3). As alrea dy discussed above, the Agency will begin to 638 apply this interpretation 90 days after publication of this document in the Federal Register

. 639

640 The Agency’s proposed policy for determini ng whether a nanoscale material is a new 641 active or inert ingredient for purposes of both FI FRA and PRIA is intended only as guidance to 642 EPA personnel and decision-makers and to pesticid e applicants. While the requirements in the 643 statute and Agency regulations are binding on EPA and the a pplicants, the proposed policy 644 described in this document would not be binding on EPA personnel, pesticid e applicants, or the 645 public. Accordingly, EPA may depart from the policy proposed herein if and when 646 circumstances warrant. Likewise, pesticide applicants may assert that the proposed policy is not 647 applicable to a specific pesticide or situati on in which EPA may be expected to apply it. 648

649

VII. Questions for Comment 650

Notwithstanding the fact that this document is announcing an interpretive rule of general 651 applicability and a separate st atement of general policy, both of which are exempt from the 652 notice and comment requirements of the Administ rative Procedure Act, EPA is inviting public 653

comment. 654

655 With respect to the interpretation, EPA is not seeking comment on whether information 656 concerning the presence of a nanoscale material in a pesticide product is or should be reportable 657 under FIFRA section 6(a)(2), but we are interested in comment on th e clarity of the interpretation 658 and whether the scope of reportable informati on should be expanded. EPA specifically invites 659 comments on the following issues: 660

661

1. Should the reporting requirement apply only to n anoscale material that is “intentionally 662 produced to have at least one dimension t hat measures between approximately 1 and 100 663 nanometers,” or should it also apply to naturally occurring materials? Why? 664

665*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 16 of 19 2. Should the reporting requirement apply to ingr edients in pesticides that contain any 666 amount of a nanoscale material, or should th e requirement apply only if an ingredient 667 contains more than a specified percentage (e.g., 10%) of nanoscale material? If the 668 latter, what should the specified percentage be and why? 669
670

3. How should the reporting requirement apply to a pesticide manufacturer who purchases 671 ingredients that may c ontain nanoscale material? 672

673 With respect to the proposed policy, EPA is seeking comment on how to implement it to 674 ensure efficient, effective, and timely review of applications. EPA specifically invites comments 675 on the following issues: 676

677
1. Is there a way to determine, in advance of receiving an application for registration of a 678 product containing a nanoscale material, whether a particular kind of nanoscale 679 material has properties that, for purposes of ri sk assessment, are essentially the same as 680 larger sized materials of the same substance? If so, how would such determinations be 681 made and on what would they be based? 682

683

2. What kinds of information should EPA accept as demonstrating that a pesticide product 684 containing a nanoscale ingredient is identical or substantia lly similar to a currently 685 registered pesticide or differs only in ways t hat would not significantly increase the risk 686 of unreasonable adverse effe cts on the environment, and t hat approving the registration 687 in the manner proposed would not significant ly increase the risk of any unreasonable 688 adverse effect on the environment? 689
690

3. Can you suggest any alternative(s) to the pr oposed policy that woul d be equally or even 691 more effective in addressing the status of nanoscale materials as new active or inert 692 ingredients for purposes of both FIFRA and PRIA, keeping in mind the growing body of 693 data showing that size, especially when re duced below approximately 100 nm, may alter 694 the manner in which materials behave and, in tu rn, the potential risk to human health 695
and the environment associated with such materials? 696

697

VIII. References 698

As indicated under ADDRESSES , a docket has been established for this document under 699 docket ID number EPA-HQ-OPP-2010-0197. The follo wing is a listing of the documents that 700 are specifically referenced in this document. The docket includes these documents and other 701 information considered by EPA, including documen ts that are referenced within the documents 702 that are included in the docket, ev en if the referenced document is not physically located in the 703 docket. For assistance in locating these other do cuments, please consul t the technical contact 704
listed under FOR FURTHER INFORMATION CONTACT

. 705

706

1. Cheng et al. 2007. Effect of carbon nanotubes on developing zebrafish ( Danio rerio ) 707 embryos. Environ. Toxicol. Chem. 26:708–716. 708
709*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 17 of 19 2. Department of Health and Human Services. Centers for Disease Control and Prevention. 710 National Institute for Occupational Safety and Health. Approaches to Safe 711 Nanotechnology: Managing the Health and Safety Concerns Associated with Engineered 712
Nanomaterials. http://www.cdc.gov/niosh/docs/2009-125/pdfs/2009-125.pdf (November 713 2009). 714

715

3. Donaldson, K. et al., 2000. Ultrafine Particles: Mechanisms of Lung Injury. Philosophical 716 Transactions: Mathematical, Physical and Engineering Sciences. 358 (1775): 2741-2749. 717

718

4. Donaldson, K. et al., 2002. Inflammation Ca used by Particles and Fibers. Inhalation 719 Toxicology. 14 (1): 5-27. 720

721

5. Duffin, R. et al., 2002. The Importance of Su rface Area and Specific Reactivity in the 722 Acute Pulmonary Inflammatory Response to Part icles. Annals of Occupational Hygiene. 723 46 (1): 242-245. 724

725

6. Federici et al. 2007, Toxicity of tita nium dioxide to rainbow trout ( Oncorhynchus 726 mykiss ): Gill injury, oxidative stre ss, and other physiological e ffects. Aquat. Toxicol. 84: 727
415–430. 728
729

7. FIFRA Science Advisory Panel (SAP). 2010. “Evaluation of Hazard and Exposure 730
Associated with Nanosilver and Other Nanomet al Pesticide Products.” Report from the 731 FIFRA Scientific Advisory Panel Meeting of November, 2009. FIFRA Scientific 732 Advisory Panel, Office of Science Coor dination and Policy, Office of Prevention, 733 Pesticides and Toxic Substances, U.S. E nvironmental Protection Agency. Washington, 734
DC. Available: http://www.epa.gov/scipoly/sap/2009

. 735

736

8. Handy et al. 2008, The ecotoxicology and chemis try of manufactured nanoparticles. 2008. 737 Ecotoxicology 17:287-314. 738
739

9. Kashiwada et al. 2006. Distribution of na noparticles in the see-through Medaka ( Oryzias 740 latipes ). Environ. Health Perspect. 114: 1697–1702. 741

742

10. Kim, Y.S. et al., 2008. Twenty-Eight Day Oral Toxicity, Genotoxicity, and Gender743 Related Tissue Distribution of Silver Nanopa rticles in Sprague-Dawley Rats. Inhalation 744 Toxicology. 20 (6): 575-583. 745

746

11. Klaine et al. 2008. Nanomaterials in the Environment: Beha vior, Fate, Bioavailability, 747
and Effects. Environ..Toxicol..Chem.. 27: 1825-1851. 748
749

12. Lovern and Klaper 2006. Daphnia magna mo rtality when exposed to titanium 750 nanoparticles and fullerene (C60) nanopart icles. Environ. Toxicol. Chem. 25: 1132–1137. 751

752

13. National Nanotechnology Initia tive. 2004. Strategic Plan. 753 http://www.nano.gov/NNI_Strategic_Plan_2004.pdf

. 754

755*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 18 of 19 14. Oberdörster, G. et al., 2005. Nanotoxicology: an emerging discipline evolving from 756 studies of ultrafine partic les. Environmental Health Perspectives. (113): 823-839. 757

758

15. Oberdorster et al. 2006. Ecot oxicology of carbon-based engi neered nanoparticles: 759 effects of fullerene (C-60) on a quatic organisms. Carbon 44: 1112-1120. 760

761

16. Roberts et al. 2007. In vivo biomodificat ion of lipidcoated carbon nanotubes by Daphnia 762

magna . Environ. Sci. Technol. 41: 3025–3029 763

764

17. SCENIHR, 2009. Risk Assessment of Pr oducts of Nanotechnologies. European 765
Commission. Directorate-General for Health and Consumers. Scientific Committee on 766 Emerging and Newly Identified Risks, Brussels: 28 th Plenary Meeting. January 19, 2009. 767 http://ec.europa.eu/health/ph_risk/co mmittees/04_scenihr/docs/scenihr_s_01.pdf

. 768

769
18. Seaton, A. et al., 2009. Nanoparticles, human h ealth hazard and regulation. Journal of the 770 Royal Society, published online at: 771 http://rsif.royalsocietypublishing.org/cont ent/early/2009/08/31/rsi f.2009.0252.focus.full#r 772
ef-14

. 773

774
19. Smith et al. 2007. Toxicity of single walled carbon nanotubes on rainbow trout 775 (Oncorhyncos mykiss): Respiratory toxicity, organ pathologies, and other physiological 776 effects. Aquat. Toxicol. 84: 415–430. 777
778

20. Wick, P. et al., U.S. Department of Health and Human Services, Nati onal Institutes of 779
Health. http://ehp.niehs.ni h.gov/members/2009/0901200/0901200.pdf

. 780

781

VIII. Applicable Statutory and Executive Order Reviews 782

EPA submitted this document to the Office of Management and Budget (OMB) for 783 review under Executive Order 12866, entitled Regulatory Planning and Review (58 FR 51735, 784 October 4, 1993). Any changes made in re sponse to OMB recommendations have been 785
documented in the docket for this action as required by section 6(a) (3)(E) of the Executive Order. 786

The various other statutory a nd Executive Order review re quirements that apply to a 787 regulatory action do not apply to th is action because this document is not a regulatory action and 788 does not otherwise impose new requirements. As indicated previously th is document clarifies 789 the applicability of the statut e and existing regulation regard ing reporting under FIFRA section 790 6(a)(2) and presents the Agency’s proposed polic y for determining whether a nanoscale material 791 is a new active or inert ingredient for purposes of both FIFRA and PRIA. 792

List of Subjects 793

Environmental protection, administrativ e practice and procedure, pesticides, 794 nanotechnology. 795

796 Dated: ________ 797*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 19 of 19 ________________ 798 Assistant Administrator for Chemical Safety and Pollution Prevention. 799
800 [FR Doc. 10–???? Filed ??–??–10; 8:45 am] 801
BILLING CODE 6560–50–S 802