U.S. Environmental Protection Agency Office of Chemical Safety and Pollution Prevention (OCSPP) 1200 Pennsylvania Avenue, N.W. (Mailcode 7101 M) Washington, D.C. 20460

OPPTS-RCS-OMB-7f (revised 11/15/2010) If you have any questions about this regulatory action or this documentation, please call the contact:

Name: eMail: Phone: Title of

Action: 

### Documentation of Changes Made During Review Under Executive Order 12866

Docket #: EPA-HQ- FRL#: RIN: 2070-

This action was submitted to the Office of Management and Budget (OMB) for review under Executive Order 12866, entitled Regulatory Planning and Review (58 FR 51735, October 4, 1993). According to section 6(a)(3)(E) of the Executive Order, whenever the Agency makes publicly available an action that was reviewed under Executive Order 12866, the Agency is also required to:

(1) Make available to the public a copy of the information that was provided to OMB's Office of Information and Regulatory Affairs (OIRA) for review under the Executive Order, i.e., the text of the draft action and, if applicable, an assessment of the potential costs and benefits; as well as additional information required for those actions that are determined to be economically significant under section 3(f) of the Executive Order (see section 6(a)(3)(B) & (C)); (2) Identify for the public any substantive changes made to the draft submitted to OMB, using a method that is complete, clear and simple; and (3) Identify for the public those substantive changes made at the suggestion or recommendation of OIRA/OMB. For this action, were substantive changes made during the review? [Check the appropriate answer.]

Yes. [The information identified in items 1-3 below is included in the docket, as applicable.] No. [Only the information identified in item 1 below is included in the docket.]

Accordingly, the Agency has included the following information in the public docket for this

action: [Check the appropriate box(es).]

(2) Documentation of any substantive changes that were made to the draft document that was submitted to OIRA/OMB for review, when compared with what completed review, using one of the following methods (select one): (1) A copy of the information that was submitted to OIRA for review under the Executive Order.

(3) Documentation of those substantive changes made at the suggestion or recommendation of
OMB , if any, are identified in the document using one of the following methods (select one): (a) A copy of the draft document submitted, with redline and strikeout to show all the substantive changes that were made during the review. (b) A document that identifies the substantive changes that were made during the review, with page and paragraph references to the draft document that was submitted.

(a) Through attributions to OMB in the redline and strikeout version or other document identifying the changes made at OMB's recommendation. (c) Other (please describe):

(b) Other (please describe):

William (Bill) Jordan j ordan.william@epa.gov 703-305-1049 Pesticides; Policies Concerning Products Containing Nanoscale Materials; Opportunity for Public Comment; Notice

OPP-2010-0197 8877-9 ZA11

A ll of the changes were made in response to OMB suggestions or recommendations. OMB serves as the control point for all comments received.*** 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

. 32

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

. 73

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

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

Page 1 of 30 EO12866_NanoPests_FRN_DRAFT _2010

- 07

- 14.doc -Revised-clean_2011-06-01.docx 1

EO 12866 Review Draft as submitted. 2

This is the final revised document as of today. Revi sed to address Interagency Comments received under EO 3

12866 review. 4

BILLING CODE 6560–50–P 5

ENVIRONMENTAL PRO TECTION AGENCY 6

[EPA–HQ–OPP–2010-0197; FRL– XXXX

– X ] 7

Pesticides; Policies Concerning Products Contai ning Nanoscale Materials; Opportunity for 8
Public Comment 9

AGENCY: Environmental Protection Agency (EPA). 10

ACTION: Notice

. 11

SUMMARY: This document describes both an interpretation several possible approaches for 12 obtaining certain additional information on the composition of a statutory requirement and a 13 separate policy pertaining to pesticide products that contain a “ . The notice focuses particularly 14
on information about what nanoscale material.” materials are present in registered pesticide 15 products. In connection with the interpretation and polic y discussed in this document, EPA is 16 defining describes “nanoscale material” as an active or in ert ingredient and any component parts 17 thereof intentionally produced to have at least one dimension that measures between 18 approximately 1 and 100 nanometers. As explained more fully in this document 19

20 Under one approach , EPA believes that would use section 6(a )(2) of the Federal 21 Insecticide, Fungicide, and Rode nticide Act (FIFRA) to obtain information regarding the 22 presence of a what nanoscale material is present in a registered pesticid e product and its potential 23
effects on humans or the environment is reportable under section 6(a)(2) of the Federal 24 Insecticide, Fungicide, a nd Rodenticide Act (FIFRA)

. S uch information must also be included

, 25
pursuant to . If EPA adopts this approach, 40 CFR 152.50(f)(3 ), ) would also require the 26
inclusion of such information wi th any application for registrati on of a pesticide product that 27
contains a nanoscale material. Under an alternative approach, EPA would obtain such 28 information using data call-in notices (DCIs) under FIFRA section 3(c)(2)(B). If EPA adopts 29 this alternate approach, EPA would also need to require the inclusion of this information with 30 any application for registration of a pesticide product that contains any nano scale material. In 31 addition, this document a nanoscale material. EPA is review ing whether this could be done under 32 existing regulations or whether EPA would need to amend existing regulations to clarify that the 33 information is required with any application fo r registration. It is EPA’s view that FIFRA 34 section 6(a)(2) is the most efficient and expe dient administrative approach to obtaining 35 information about nanoscale materials in pesticides and EPA would prefer to use this approach. 36
This document also proposes a new approach for how EPA will determine on a case-by-case 37 basis whether a nanoscale active or inert ingredie nt is a “new” active or inert ingredient for 38 purposes of FIFRA and the Pesticide Registra tion Improvement Act (PRIA), even when an 39*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 2 of 30 identical, non-nanoscale form of the nanos cale ingredient is al ready registered. 40 Notwithstanding the fact that this document is announcing an interpre tive rule of general 41 applicability and a separate st atement of general policy, both of which are exempt from the 42 notice and comment requirements of the Administrative Procedure Act, EPA is soliciting public 43 comment on the clarity of the reporting requirement as it pertains to the presence of nanoscale 44
material s in pesticide product s. EPA is also asking for specific input on the proposed policy for 45 determining whether a nanoscale mate rial is “new” under FIFRA and PRIA

. 46

47 After considering any public comments on th e use of FIFRA section 6(a)(2) or DCIs 48 under FIFRA section 3(c)(2)(B), as well as pub lic comments submitted in response to other 49 questions posed in this Notice, EPA plans to i ssue a subsequent Notice in the Federal Register 50 announcing its approach to gather this informati on. EPA is also asking for specific input on the 51 proposed approach for determining whether a nanoscale material is “new” under FIFRA and 52

PRIA. 53
54
DATES: Comments must be recei ved on or before [ 45 ] insert 30 days after the date of 55 publication in the Federal Register

. ]. 56

ADDRESSES: Submit your comments, identified by doc ket identification (ID) number EPA– 57 HQ–OPP–2010–0197, by one of the following methods: 58

• Federal eRulemaking Portal : http://www.regulations.gov

. http://www.regulations.gov

. 59 Follow the on-line instructions for submitting comments. 60

• Mail : Office of Pesticide Programs (OPP) Regulatory Public Docket (7502P), 61 Environmental Protection Ag ency, 1200 Pennsylvania Ave ., NW., Washington, DC 20460–0001. 62

• Delivery : OPP Regulatory Public Do cket (7502P), Environmental Protection Agency, 63 Rm. S–4400, One Potomac Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, VA. Deliveries 64 are only accepted during the Docket Facility’s no rmal hours of operation (8:30 a.m. to 4 p.m., 65 Monday through Friday, excluding legal holidays) . Special arrangements should be made for 66 deliveries of boxed information. The Docket Facility telephone number is (703) 305–5805. 67

Instructions : Direct your comments to docke t ID number EP A–HQ–OPP–2010-0197. 68 EPA's policy is that all comments received will be included in the docket without change and 69 may be made available on-line at http://www.regulatio ns.gov , http://www.regulations.gov

, 70 including any personal information provided, un less the comment includes information claimed 71 to be Confidential Business Information (CBI) or ot her information whose disclosure is restricted 72 by statute. Do not submit information that you cons ider to be CBI or ot herwise protected through 73 regulations.gov or e-mail. The regulations.gov website is an “anonymous access” system, which 74 means EPA will not know your identity or contac t information unless you provide it in the body 75 of your comment. If you send an e-mail co mment directly to EP A without going through 76 regulations.gov, your e-mail address will be automati cally captured and included as part of the 77 comment that is placed in the docket and made available on the Internet. If you submit an 78 electronic comment, EPA recomme nds that you include your name and other contact information 79 in the body of your comment and with any disk or CD-ROM you submit. If EPA cannot read 80 your comment due to technical difficulties and cannot contact you for clarification, EPA may not 81*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 3 of 30 be able to consider your comment . Electronic files should avoid the use of special characters, 82 any form of encryption, and be fr ee of any defects or viruses. 83

Docket : All documents in the docket are list ed in the docket index available at 84 http://www.regulations.gov . Although listed in the index, so me information is not publicly 85 available, e.g., CBI or other information whose disc losure is restricted by statute. Certain other 86 material, such as copyrighted material, is not pl aced on the Internet and will be publicly available 87 only in hard copy form. Publicly available docket materials are ava ilable either in the electronic 88
docket at http://www.regulations.gov , or, if only available in ha rd copy, at the OPP Regulatory 89 Public Docket in Rm. S–4400, One Potomac Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, 90 VA. The hours of operation of this Docket Facil ity are from 8:30 a.m. to 4 p.m., Monday through 91 Friday, excluding legal holidays. The Docket Facility telephone number is (703) 305–5805. 92

FOR FURTHER INFORMATION CONTACT: Demson Fuller Jed Costanza , Antimicrobials 93 Division (7510P), Office of Pesticide Pr ograms, Environmental Protection Agency, 1200 94 Pennsylvania Ave., NW., Washingt on, DC 20460–0001; telephone number: 703- 308

- 8062 347- 95

0204 ; fax number: 703-308-8005; e-mail address: 96
fuller.demson @epa.gov

. costanza.jed@epa.gov

. 97
98
SUPPLEMENTARY INFORMATION: 99
100
I. General Information 101

102

A. Does this Action Apply to Me? 103

104 This action is directed to those persons w ho manufacture, distri bute, sell, apply, or 105 regulate pesticide products, includi ng agricultural, commercial, a nd residential products (NAICS 106 codes 32532 and 32561). This listing is not intended to be exhaustive, but rather provides a 107 guide for readers regarding entities likely to be affected by this act ion. Other types of entities not 108
listed in this Unit could also be affected. The North American Industrial Classification System 109 (NAICS) codes have been provide d to assist you and others in determining whether this action 110 might apply to certain entities. If you have any questions regard ing the applicability of this 111 action to a particular entity, consult the person listed under FOR FURTHER INFORMATION 112

CONTACT. 113

114

B. What Should I Consider as I Prepare My Comments for EPA? 115

116

1. Submitting CBI . Do not submit this information to EPA through regulations.gov or e117 mail. Clearly mark the part or all of the information that you claim to be CBI. For CBI 118 information in a disk or CD-ROM that you mail to EPA, mark the outside of the disk or CD119 ROM as CBI and then identify electronically within the disk or CD-ROM the specific 120
information that is claimed as CBI. In addition to one complete version of the comment that 121 includes information claimed as CBI, a copy of the comment that does not contain the 122 information claimed as CBI must be submitted for inclusion in the public docket. Information so 123 marked will not be disclosed except in accordance with procedures set forth in 40 CFR part 2. 124
125

2. Tips for preparing your comments . When submitting comments, remember to: 126*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 4 of 30 127 i. Identify the document by docket ID number and other identifying information (subject 128 heading, Federal Register date and page number). 129

130 ii. Follow directions. The Agency may ask you to respond to specific questions or 131 organize comments by referencing a Code of Federal Regulations (CFR) part or section number. 132

133 iii. Explain why you agree or disagree; suggest alternatives and substitute language for 134 your requested changes. 135

136 iv. Describe any assumptions and provide a ny technical information and/or data that you 137
used. 138
139 v. If you estimate potential costs or burdens, explain how you arrived at your estimate in 140 sufficient detail to allow for it to be reproduced. 141

vi. Provide specific examples to illustra te your concerns and suggest alternatives. 142

vii. Explain your views as clearly as possible , avoiding the use of pr ofanity or personal 143
threats

. 144
145 viii. Make sure to submit your comments by the comment period deadline identified. 146

147 II. Applicable Statutory and Regulatory Requirements 148
149 As a general matter, pesticides may not be sold or distributed in the United States unless 150 they are registered with the EPA. FIFRA secti on 3(a) (7 U.S.C. 136a(a)). In order to obtain a 151 pesticide registration, an app licant must provide EPA with data (or cite existing data) 152 demonstrating that the proposed registration co mplies with the requirement for registration. 153 FIFRA section 3(c)(1)(F) (7 U.S.C. 136a(c)(1)(F)) . FIFRA contains two provisions under which 154 EPA may register pesticides: se ction 3(c)(5) for “unconditional” registration and section 3(c)(7) 155 for “conditional” registration (7 U.S.C. 136a(c)(5 ) and 7 U.S.C. 136a(c)(7)). Importantly, EPA 156 must make statutorily required findings for each and every pesticide product for which 157 registration is sought, regardless of whether another pesticide pr oduct with the same or similar 158 composition and use patterns is already registered. 159

160 The standard for determining whether an app lication should be granted unconditionally is 161 found in FIFRA section 3(c)(5). This section provides that, in order to grant a registration, EPA 162 must find that a product’s com position warrants the proposed claims for it; that the product’s 163 labeling and other material required to be subm itted comply with FIFRA; that the product will 164 perform its intended function without causing un reasonable adverse effects on the environment; 165 and that, when used in accordance with wide spread and commonly recognized practice, the 166 product will not cause unreasonable adve rse effects on the environment. 167

168
FIFRA defines “unreasonable adverse effect s on the environment” as including “any 169 unreasonable risk to man or the environment, taking into account the economic, social, and 170
environmental costs and benefits of the use of any pesticide.” FIFRA section 2(bb) (7 U.S.C. 171*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 5 of 30 136(bb)). Thus, a critical aspect of determin ing whether or not a pe sticide product should be 172 granted a registration is an eval uation of whether the benefits associated with the use of a 173 pesticide exceed outweigh the risks associated with such use. The burden of demonstrating that a 174 product meets the standards for registration rests at all times on the registrant or applicant for 175 registration. See, e.g. Industrial Union Dept. v. American Petroleum Institute, 448 U.S. 607, 653 176 n. 61 (1980); Environmental Defense Fund v. EPA, 510 F.2d 1292, 1297, 1302 (D.C. Cir. 1975). 177

178 The Agency has promulgated regulations in 40 CFR parts 158 and 161 which identify the 179 types of data EPA expects an applicant to provid e to support an application for registration of a 180 pesticide product. The Agency requ ires a wide variety of studies in order to evaluate whether a 181 pesticide will cause unreasonable adverse effect s on the environment. These required studies 182 include both toxicity tests and da ta to characterize e xposure to a pesticide, including extensive 183 information on a product’s composition, and its fate in the environment and within the human 184 body. For certain pesticides EPA also requires data on product efficacy. 185

186 If an applicant cannot provide necessary da ta for EPA to make the determinations 187 required to register a product unconditionally und er FIFRA section 3(c)(5), EPA may still be 188 able to register the product “conditionally” under FIFRA section 3(c)(7). FIFRA section 3(c)(7) 189 authorizes EPA to register a pesticide product on th e condition that the applicant provides 190 additional data necessary to s upport a finding that the product meet s the statutory standards in 191 FIFRA section 3(c)(5). FIFRA section 3(c)(7 ) authorizes conditional registration in three 192 circumstances. First, the Agency may condition ally register a product if EPA determines, among 193 other things, that the product is identical or substantially similar to a currently registered 194 pesticide or differs only in wa ys that would not significantly increase the risk of unreasonable 195 adverse effects on the environment, and that approving the registration in the manner proposed 196 would not significantly increase the risk of any unreasonable adverse effect on the environment. 197 FIFRA section 3(c)(7)(A) (7 U.S.C. 136a(c)(7)(A)) . Products approved unde r this authority are 198 commonly called “me-too registratio ns.” Second, EPA may register a pesticide for an additional 199 use, if the applicant provides da ta to evaluate the safety of the new use, and use of the product 200 would not significantly increase the risk of unr easonable adverse effects on the environment 201 compared to products already registered. FIFR A section 3(c)(7)(B) (7 U.S.C. 136a(c)(7)(B)). 202 These product approvals are referred to as “new use” registrations. Finally, EPA may 203 conditionally register a pesticide product that contains an active ingredient not present in any 204 currently registered pesticide product, if the Administrato r determines that: 205

206

1

. ). The applicant has provided all data necessary to evaluate the safety of the pesticide, 207 with the exception of any data which are lack ing because the applican t has not had enough time 208 to generate the data since learning of the requirement; 209

210

2

. ). Use of the pesticide during the time peri od needed to develop the additional data will 211
not cause unreasonable adverse e ffects on the environment; and 212

213

3

. ). Use of the pesticide is in the public interest. 214
215 FIFRA section 3(c)(7)(C) (7 U.S.C. 136a(c)(7)(C)). 216

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

Page 6 of 30 As with applications for unconditional re gistrations, applicants for conditional 218 registration bear the burde n at all times of demons trating that the statutor y standards are met. 219

220 The Agency’s interest in data to evaluate the risks and benefits of a pesticide does not 221 necessarily end once EPA has registered a pestic ide product. Accordingly, other provisions of 222 FIFRA allow the Agency to require pesticide re gistrants to develop a nd submit information the 223 Agency believes it needs in order to main tain the registration of pesticide products. 224

225

A. Data Call-in 226

227 Under FIFRA section 3(c )(2)(B), EPA may send a data call-in notice (DCI) to a 228 registrant requiring the registra nt to provide additional data or other information, which the 229 registrant may need to generate or compile. Sp ecifically, “if the Administrator determines that 230 additional data are required to maintain in eff ect an existing registrati on of a pesticide, the 231 Administrator shall notify all existing registrant s of the pesticide to which the determination 232 relates and provide a list of such registrants to any interested person.” Failure to respond to the 233 DCI can serve as the basis for suspending the registration of the pr oduct, thereby making it 234 unlawful for the registrant to se ll or distribute the pesticide. 235
236 Generally, EPA’s determination that additional data are needed is contemplated to occur 237 for one of the following five reasons: 238
239 1). The Re-registration Program. Section 4 of FIFRA requires EPA to re-assess the health 240 and safety data for all pestic ide active ingredients register ed before November 1, 1984, to 241 determine whether these “older” pesticides meet the criteria for registration that would be 242 expected of a pesticide being registered today for the first time. Section 4 directs EPA to use 243 Section 3(c)(2)(B) authority to obtain the required data. 244
245 2). The Registration Review Pr ogram. Section 3(g) of FIFRA contains provisions to help 246 achieve the goal of reviewing each pesticide every 15 years to assure that the pesticide continues 247 to pose no risk of unreasonable adverse effects on human health or the environment. Section 248 3(g) instructs EPA to use the section 3(c)(2)(B) authority to obtain the required data. 249
250 3). Anticipated Residue/Percent Crop Treat ed Information. Unde r section 408 of the 251 Federal Food, Drug and Cosmetic Act (FFDCA), be fore a pesticide may be used on food or feed 252 crops, the Agency must establish a tolerance for the pesticide residues on that crop or establish 253 an exemption from the requirement to have a to lerance. Section 408(b)(2 )(E) and (F) of FFDCA 254 authorize the use of anticipated or actual residue (ARs) data a nd percent crop treated (PCT) data 255 to establish, modify, maintain, or revoke a tolera nce for a pesticide. The FFDCA requires that if 256 AR data are used, data must be reviewed five years after a tolerance is initially established. 257
258 4). The Special Review Program. EPA may c onduct a Special Review if EPA believes 259 that a pesticide poses risks of unreasonable advers e effects on human health or the environment. 260

In addition, the Special Review Program, EP A focuses on specific hazards or uses of a pesticide. 261 Special Reviews are not intended to be comprehens ive evaluations of the pesticide; instead the 262 Special Review DCIs are to address the specific h azard or exposure concerns that are at issue. 263

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

Page 7 of 30 5). Enforcement and Unanticipated Circumstances. The need for a DCI may arise from 265 the discovery of deficiencies in previously submitted data, or from the discovery of specific 266 attributes of the pesticide or its ingredients. This may lead the agency to determine that 267
additional information is necessa ry to reassess whether the pes ticide will cause unreasonable 268 adverse effects on the environment. This type of DCI is needed b ecause the concern and 269
therefore the need for data arise not from a mandated review program like Re-registration or 270 Registration Review described a bove, but from unanticipated ci rcumstances. Section 3(c)(2)(B) 271 of FIFRA provides a means of obtaining any needed data

. 272

273

B. FIFRA section 6(a)(2) 274
275 FIFRA section 6(a)(2) provides that registrants must inform the Agency of certain 276 relevant information relating to their products, even though it wa s not specifically requested by 277 EPA. Specifically, FIFRA section 6(a)(2) requires that, “[i]f at any time after the registration of 278 a pesticide the registrant has additional fact ual information regardi ng unreasonable adverse 279
effects on the environment of the pesticide, the registrant shall submit such information to the 280 Administrator.” (7 U.S.C. 136d(a)(2)). For over thirty years, EPA ha s interpreted this provision 281 expansively to include not only information re lating directly to adverse effects caused by 282 pesticides, but also to other types of informa tion and studies that EPA would typically use in 283 assessing whether a pesticide meets the statutory standard for registrati on (i.e., the “unreasonable 284
adverse effects on the environm ent” risk/benefit standard). See 43 FR 37611 (August 23, 1978). 285

286 In 1997, EPA promulgated a final rule at 40 CFR part 159, subpart D in the Federal 287 Register issue of September 19, 1997 (62 FR 49370)(FRL-5739-1), setting forth EPA’s 288 interpretation and enforcement policy regarding FIFRA section 6(a)(2). The rule explains, 289 among other things, what information EPA regards as “additional” and “factual,” as well as how 290 quickly and to whom such information must be reported. The regulation specifies many kinds of 291 information, from varied scientific disciplines, that EPA requires regist rants to submit pursuant 292 to FIFRA section 6(a)(2). The types of informati on reflect the variety of scientific data used by 293 EPA in making the statutorily required determin ations – whether pesticides cause unreasonable 294 adverse effects on the environment. Thus, fo r example, the regulations generally require 295 registrants to report studies indicating that a pes ticide causes new or a high er incidence of toxic 296 effects than previously identified (see 40 CFR 159.165) and to report inci dents involving injury 297 to humans, pets or wildlife resulting from exposure to a pesticide (40 CFR 159.184). But, EPA 298 uses other types of information that do not dir ectly demonstrate advers e effects in its risk 299 assessments, and new factual information of this kind is also reportable und er the regulation. For 300 example, registrants must report studies that identify new metabolites, degradates, impurities, or 301 contaminants of pesticides (40 CFR 159.179); cert ain information on the detection of pesticide 302 residues in water, food, and feed (40 CFR 159.1 78); and new studies of human exposure (40 303 CFR 159.170). In sum, EPA’s regulation requi res reporting of many types of information 304 relevant to EPA’s assessment of the safety of a pesticide product – in the words of section 305 6(a)(2) “information regarding unrea sonable adverse effects on the environment of the pesticide” 306 – not merely information that dire ctly concerns adverse effects. 307

308 In promulgating that regulation, however, EPA also recognized it was impossible to 309 establish rules addressing every type of factual information that might become relevant in the 310*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 8 of 30 future to judging whether a registered pesticid e product continued to meet the FIFRA statutory 311 standards. Accordingly, 40 CFR 159.195( c a ) provides: 312

313 “The registrant shall submit to the Administra tor information other than that described in 314 §§159.165 through 159.188 if the registrant knows, or reasonably should know, that if the 315 information should prove to be correct, EPA might regard the information alone or in 316 conjunction with other informa tion about the pesticide as raising concerns about the 317 continued registration of a product or about the appropriate terms and conditions of 318 registration of a product.” 319

320 In addition, 40 CFR 159.195( c) provides that: 321

322 “[t]he registrant shall su bmit . . . information other than that described in §§159.165 323 through 159.188 if the registrant has been informed by EPA that such additional 324 information has the potential to raise ques tions about the conti nued registration of a 325 product or about the appropriate terms and conditions of regist ration of a product.” 326

327 In light of the preceding, it must be emphasized that EPA is not expanding its 328 interpretation of FIFRA sectio n 6(a)(2) or changing its regulations through this document

. 329 Rather, consistent with EPA’s s ection 6(a)(2) regulations, EPA is merely identifying a set of 330
information

, to which the FIFRA section 6(a)(2) reporting requirement already appl ies

, t hat is 331
broader than the subset of reportable s ection 6(a)(2) data explicitly identified at present under the 332

s ection 6(a)(2) regulations

. 333

334 Further, the Agency notes that the identif ication of information as reportable under 335 FIFRA section 6(a)(2) does not necess arily mean that any particul ar pesticide or group of 336 pesticides, to which such information pertains, poses a risk. Rather, the requirement merely 337
indicates that EPA has determined that a particular type of info rmation is relevant to, and may 338 improve the A gency’s ability to assess, the safety of a pesticide. 339

340 Thus, once the Agency has informed registrant s that EPA considers a particular type of 341 information relevant to determining whether a pe sticide has the potential to cause unreasonable 342 adverse effects on the environment, that type of information becomes reportable under FIFRA 343 section 6(a)(2). 344
345 Finally, EPA promulgated a regulation in the Federal Register of May 4, 1988 (53 FR 346 15952)(FRL

- 3266

- 96) concerning at 40 CFR part 152 addressing the submission of applications 347 for registration at 40 CFR part 152

. (53 FR 15952, May 4, 1988) (FRL-3266-96). That rule 348 specifies, among other things, certain types of information that an application for registration of a 349 pesticide product must contain. The rule provides that the applicant mu st “furnish with his 350 application any factual information of which he is aware regarding unreasonable adverse effects 351 of the pesticide on man or the environment, which would be required to be reported under 352 FIFRA section 6(a)(2), if th e product were registered.” ( 40 CFR 152.50(f)(3). 353
354 Registrants’ compliance with section 6(a )(2) and EPA’s implementing regulations in 40 355

CFR Parts 152 and 159 ensures that EPA has access to any additional factual information that 356 could be important for determining whether a prev ious Agency decision to register a pesticide 357*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 9 of 30 remains a correct one, and whether a registered pesticide can in fact be used without posing 358
unreasonable adverse effects to human health an d the environment. This provision of FIFRA 359 recognizes that registrants may come into the possession of important new information that was 360 not anticipated by the Agency or of informati on the importance of which was not previously 361 known, and that in the absence of registrant s submitting such information, EPA might well 362
remain unaware of the information. Thus, section 6(a)(2) and Part 159 serve to provide an 363 important ongoing check on the correctness of the or iginal decision to regi ster a pesticide. 364 Failures to report required information, or delays in reporting, are regarded by EPA as violations 365 of FIFRA section 6(a)(2), which in turn makes them actionable under FIFRA sections 366 12(a)(2)(B)(ii) and 12(a)(2)(N) (7 U.S.C. 136j(a)(2)(B)(ii) and 7 U.S.C. 136j(a)(2)(N)). 367

III. EPA’s Interest in Nanoscale Ma terials as Pesticide Ingredients 368

A

. Applicable Definition of “ Nano scale Material” 369
370
With FIFRA section 6(a)( 2) as a backdrop, the focus of this document turns next EPA believes 371
that certain information concerni ng pesticide ingredients, which a pplicants and registrants have 372 not routinely provided previously, is relevant to the topics of nanotechnology and Agency’s 373 statutory obligation to determine whether the re gistration of a pesticide may cause unreasonable 374
adverse effects on the presence of environment. For the reasons discussed below, EPA is 375 particularly interested in nanoscale materials as either active ingredients or inert ingredients in 376 this context. Accordingly, EPA is considering how to collect information about what nanoscale 377
materials are in pesticide products . At the outset, it and is therefore so liciting public comment on 378 two possible approaches. It is important to first clarify some key ter minology that how the term 379
“nanoscale material” is being used for purpos es of this document. 380

381

A. “Nanoscale Material” 382

383 To date, EPA has not develope d formal definitions for the terms “nanotechnology” or 384 “nanoscale materials” or any similar te rms for regulatory purposes under any statute 385 administered by the Agency. Broad definitions for the terms “nanotechnology” or “nanoscale 386
materials” and discussions of nanotechnology genera lly reflect the same common elements, 387 namely: 388
389

1

. ). The material’s particle size measures typically between approximately 1 and 100 390 nanometers in at least one dimension; 391
392

2

. ). The material exhibits unique or novel properties compared to larger particles of the 393 same material; and 394
395

3

. ). Rather than occurring naturally, the mate rial has been manufactured or engineered at 396
the nanoscale to take advantage of these unique propertie s. See, for example, the definition from 397 the National Nanotechnology Initiative at: http://www.nano.gov/html /facts/whatIsNano.html

. 398
399 These elements do not readily work for in a regulatory definition context because of the 400 high degree of subjectivity i nvolved with interpreting such phrases as “unique or novel 401*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 10 of 30 properties” or “manufactured or engineered to take advantage of these properties.” Moreover, 402 the contribution of these subjective elemen ts to risk has not been established. 403

404 Instead, OPP will focus on more objective criteria in its definition of describing when 405
information about a “nanoscale material .” In connection with ” in a pesticide product may be 406 relevant to determining whether the interpretation and polic y discussed product has an 407 unreasonable adverse environmental effect. Sp ecifically, such information may be relevant in 408
this document

, OPP defines “nano scale material” as a n context when the active or inert ingredient 409 and any component parts thereof is intentionally produced to have at least one dimension that 410 measures between approximately 1 and 100 nanometers

. , regardless of the aggregation or 411 agglomeration state of the final material. 412

413 In determining whether an ingredient meets this de f scr i ni p tion, EPA will may review 414 particle size data and , among other things, the manufacturing process to determine whether it 415 employs processes specifically to create or enhance the propor tion of nanoscale materials in the 416 product, as compared with other processes used to produce similar products. The Agency 417 generally expects that these ingredients may comprise, but are not limited to, metal-based (e.g., 418 silver) and carbon-based (e.g., ca rbon nanotubes) nanoscale materials. The Agency does not, 419 however, intend this description to cover biol ogical materials (e.g., DNA, RNA, proteins) or 420
materials in their natural state (e.g., clays). To the extent that the application of this description 421 to a particular product or ingr edient is unclear, EPA would re view information provided by a 422 registrant or applicant concer ning the composition of the pest icide product and to provide an 423 Agency view on whether the product did (or did not) contain a nanoscale material for purposes 424 of this policy. 425

426

B. Potential of Nanoscale Materials to Affect Human Health and the Environment Adversely 427

428 There is a growing body of scientific evid ence showing that differences can exist 429 between nanoscale material(s) and th eir non-nanoscale counterpart(s) (Ref. 14 1 ) . Nanoscale 430 materials may have different or enhanced pr operties – for example, electrical, chemical, 431 magnetic, mechanical, thermal, or optical properties – or features, such as improved hardness or 432 strength, that are highly desirable for applications in commercial, medical, military, and 433 environmental sectors (Ref. 13 2 ). These properties are a direct c onsequence of small size, which 434 results in a larger surface area per unit of vol ume and/or quantum effects that occur at the 435 nanometer scale (i.e., 1 x 10 -9 meters). Small size itself is al so a desirable property of nanoscale 436 materials that is exploited for miniaturization of applications/p rocesses and/or stabilization or 437 delivery of payloads to diverse environmen ts or incorporation into diverse products. 438
439

A Nanoscale materials have a range of potentially beneficial public and commercial 440 applications, including medicine and public health, clean energy through more efficient solar panels, 441 pollution reduction and environmental cleanup, and improved products such as stronger, lighter, and 442 more durable or conductive materials. These benefits arise from the distinctive properties of 443 nanoscale materials, in that they are potentially more interactive or durable than other chemicals as a 444 result of their size and composition. EPA sees the emergence of nanoscale materials as offering 445 potential benefits for society in many different fields, including pest control products. The use of 446 nanoscale materials in pesticide products and treated articles may allow for more effective 447 targeting of pests, use of sma ller quantities of a pesticide, and minimizing the frequency of 448*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 11 of 30 spray-applied surface disinfection. These c ould contribute to improved human and 449 environmental safety and could lower pest co ntrol costs. For example, as a materials 450 preservative, nanosilver should ma intain its efficacy longer and require smaller quantities than 451 other silver preservatives due to an expected gradual and controll ed release of silver as opposed 452 to the rapid release of for example, silver from a zeolite structure or the immediate dissolution of 453
a silver salt. Therefore EPA seeks to encourage innovative work in developing nanoscale 454
materials to realize these benefits. 455
456 However, a number of organizations have considered whether the small size of nanoscale 457 materials or the unique or enhanced properties of nanoscale materials may, under specific conditions, 458 pose new or increased hazards to humans and the environment . Government, academic, and private 459 sector scientists in multiple c ountries are performing research in to the human health effects of 460 diverse nanoscale materials, resulting in a s ubstantial and rapidly gr owing body of scientific 461
evidence. These research findings point generally to the possibility for nanoscale materials to 462

a dversely affect human health and the environment. Research also indicates , however, that not 463 all materials in the nanoscale size range behave differently from larger sized materials of the 464
same substance. Recently, governmental and expert peer review organizations have reviewed 465
and summarized this evidence and offered views about the implications of this evidence for 466 environmental and human health and safety. 467

468 For instance, in 2009, t he National Institute of Occupati onal Safety and Health (NIOSH) 469 issued a report, “Approach es to Safe Nanotechnology: Managing the Health and Safety Concerns 470 Associated with Engi neered Nanomaterials,” which summarized the available scientific 471
information about nanoscale materials and identifi ed the following potentia l health and safety 472 properties: 473

474

 “Nanomaterials have the greatest potential to enter the body through the respiratory sys475 tem if they are airborne and in the form of respirable-sized particles (nanoparticles). They 476 may also come into contact with the skin or be ingested.” 477

478

 “Based on results from human and animal st udies, airborne nanopart icles can be inhaled 479 and deposit in the respiratory tract; and ba sed on animal studies, nanoparticles can enter 480 the blood stream, and translocate to other organs.” 481

482

 “Experimental studies in rats have shown that equivalent mass doses of insoluble 483 incidental nanoparticles are more potent than large particles of similar composition in 484 causing pulmonary inflammation and lung tumo rs. Results from in vitro cell culture 485 studies with similar materials are genera lly supportive of the biological responses 486
observed in animals.” 487

488

 “Experimental studies in animals, cell cultu res, and cell-free systems have shown that 489 changes in the chemical composition, crystal st ructure, and size of particles can influence 490 their oxidant generation prope rties and cytotoxicity.” 491
492

 “Studies in workers exposed to aerosols of some manufactured or incidental microscopic 493 (fine) and nanoscale (ultrafine) particles ha ve reported adverse lung effects including 494 lung function decrements and obstructive and fi brotic lung diseases. The implications of 495*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 12 of 30 these studies to engineered nanoparticles, wh ich may have different particle properties, 496
are uncertain.” 497
498

 “Some nanomaterials may initiate catalytic reactions depending on their composition and 499
structure that would not othe rwise be anticipated based on their chemical composition.” 500
501 (Ref. 2 3 ). 502
503 Earlier the same year, the Scientific Committee on Emerging and Newly Identified 504 Health Risks (SCENIHR), an independent scientific committee advising the European 505
Commission’s Health and Consumer Directorate, issued a report , “Risk assessment of products 506 of nanotechnologies.” The SCENIH R report identified properties similar to those identified in 507 the NIOSH report: 508
509 “Some specific hazards, discussed in the cont ext of risk for human health, have been 510 identified. These include the possibility of some nanoparticles to induce protein 511 fibrillation, the possible pathological e ffects caused by specific types of carbon 512 nanotubes, the induction of genotoxic ity, and size effects in terms of 513
biodistribution.” 514
515
and: 516
517 “For some nanomaterials, toxic effects on environmental organisms have been 518 demonstrated, as well as the potential to transfer across environmental species, 519 indicating a potential for bio accumulation in species at the end of that part of the 520
food chain.” 521
522 (Ref. 1 7 4 ). 523
524
In another recent surv ey of scientific research on nanoscale materials, the authors 525 reported: 526
527 “Many studies have examined the pro-infl ammatory effects of manufactured NPs 528 [nanoparticles], on the basis that their ab ility to cause inflammation is a major 529 predictor of potential hazard in such particles. The firs t important finding was that 530 NPs have a more pronounced effect on inflammation, cell damage and cell 531 stimulation than an equal mass of particle s of the same materi al of greater size [ ( Ref

. 532 3)]

. [...]. This appears to hold true for material s as varied as carbon black, titanium 533 dioxide, various metals and polystyrene [ ( Ref. 5 )]

. [...]. Surface area is the metric 534 driving the pro-inflammatory eff ects and this is evident both in vitro [ ( Ref. 4 )] [...] 535
and in vivo [ ( Ref. 5 )]

, [...], particles of various sizes producing inflammatory effects 536 that are directly related to the surface area dose.” 537
538 (Ref. 1 8 ). 539
540
541 (Ref. 5 [reference numbers in the original were omitted]). 542*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 13 of 30 543 Other reports in the scientific literature ha ve indicated that some nanoscale materials may 544 cross the placental barrier (Ref. 2 0 6 ) or translocate to diverse organs following oral exposure 545 (Ref. 10 7 ). Once in these diverse sites and organs, the large surface area of nanoscale materials 546 may facilitate increased r eactivity and/or an inflammatory respons e, resulting in toxic effects. 547
548 Two recent literature surveys describe a br oad range of effects in non-mammalian species 549 following exposure to nanoscale materials (Refs. 8 and 11 9 ). These include, for example, 550 increased ventilation rates, mucu s production, and pathologies, a nd related alteration of enzyme 551
activities and indicato rs of oxidative stress in rainbow trout, Oncorhyncus mykiss (Refs. 6 10 and 552
19 11 ), and ingestion and accumulation of nanoscale ma terial in the digestive tract, as well as 553 mortality, increased heart rate s, and reduced fecundity in Daphnia magna (Refs. 12, 15 13 , and 554

1 6 14 ). Translocation of nano-scale materials from gill and gut surface to blood and other organs 555 in exposed Medaka, Oryzius latipes , has also been reported (Ref. 9 15 ) and carbon nanotubes, 556 although unable to cross the egg surface, have been shown to delay hatching in zebrafish, Danio 557

rerio (Ref. 1 ). 16). A recent review of le thal and effects concentrations determined for a wide 558 variety of species showed that some nanoscal e materials, including nano-titanium, nano-zinc 559 oxide, nano-silver, nano-copper oxide, C60, and single- and multi-walled carbon nanotubes, 560
would be classified as harmful to extrem ely toxic to non-mammalian species (Ref. 17). 561
562 While the reports and articles cited above previously have focused primarily on 563
differences between nanoscale material and conven tionally sized material of the same substances, 564
EPA has also consulted with the FIFRA Scientific Advisory Panel (SAP) on the extent to which 565 different types of nanoscale materi als may display differe nt properties. (The SAP is a federal 566 advisory committee consisting of external, indepe ndent, expert, scientific peer reviewers who 567 provide advice to EPA on scientific issues involved in the regulati on of pesticides.) In response 568 to EPA questions on how size and other properties of nanoscale materials potentially affect risk 569 and how to assess such risks, the SAP said: “Exi sting data clearly indicate that many properties 570 of particles change with size, in cluding rate of release of ioni c forms of metal, reactivity or 571 catalytic efficiency, Plasmon resonance, and quantum effects. . . . The effect of particle size on 572 biological responses to particle e xposure is less well defined.” (Ref. 7 18 ). The SAP also noted 573 that “[o]ther physicochemical prope rties, such as shape, charge and surface coating, are also 574 likely to impact biological respon se and environmental fate [of nanoscale materials]. . . . The 575 lack of a clear understanding of how particle size and other ph ysical properties affect hazard 576 profiles led most Panel members to be unsuppor tive of bridging among silver-based materials 577 with different properties.” (Ref. 7 18 ). 578
579 It is important to emphasize that , while the conclusions described above previously apply 580 generally to the class of nanoscale materials, an specific material(s) and or context in which the 581 study was conducted, any individual type of nanomaterial nanoscale material may not display all 582 or even any of the characteristics observed and reported for other nanoscale materials. In other 583 words, some nanoscale materials may have proper ties which, for purposes of assessing the risk 584 of a pesticide, are essentially identical to larger sized materials (or particles) of the same 585 substance. Furthermore, nanoscale materials may al so have properties that make them less risky, 586 or more beneficial in some other way, th an larger sized materials (or particles) of the same 587 substance. So, it appears increasingly likely th at there are few, if a ny, universal “nanoscale” 588 effects, and the distinctive effects seen at nanoscale are specific to the properties of each material 589*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 14 of 30 type under specific exposure scenarios. Thus, EP A does not regard the fact that an ingredient 590
meets our de f scr i ni p tion of a nanoscale material as eviden ce that a pesticide containing the 591 ingredient would cause unreasonable adverse effect s on the environmental and thus would no 592 longer meet s the statutory standards for registration. Ra ther, the presence of a nanoscale material 593 in a pesticide is grounds for EPA to consider the possible need for data to characterize the 594 potential of the ingredient to pose risks. However, the registrati on status of a product would not 595 change merely as a result of providing informa tion to EPA about the presence of a previously596 unreported nanoscale material. If, based on a sc ience based assessment of the risks of the 597 specific pesticide ingredients i nvolved, EPA were to determine that the pesticide no longer met 598 the criteria for registration, or that some change was needed in the conditions of use, EPA would 599 conduct a separate action to notify the manufactur er of that determination, consistent with 600 current FIFRA regulations. 601

602 Finally, scientifically speaking, there currently is no bright li ne with respect to a size 603 below (or above) which nanoscale materials do (or do not) exhibit properties that might rai se risk 604

concerns. be of interest in assessing whether a pesticide product has the potential to cause 605
unreasonable adverse effects on the environment. Therefore, the precise size range in 606 nanometers addressed by the policies announced proposed in this document are subject to 607 change might be revised in the future as new information becomes available. 608
609

C. Nanoscale Materi als and Pesticides 610

611 The Agency has information indicating that the use of nanotechnology has started to 612 expand into pesticide products, as it already has in many other fields . For instance, a number of 613 companies have contacted EPA expressing an inte rest in obtaining regist rations for pesticide 614 products containing ingredients identified as na nosilver or nanosilver composite structures 615 (jointly referred to as “nanosilver ”) ”), and several companies have submitted applications to 616 register pesticides containing nanosilver. In addition, EPA now has information suggesting that 617 there are other pesticide products currently registered and in the marketplace that contain 618 nanosilver as an active ingredient. 619

620 As already summarized above, i n In order for EPA to fulfill its responsibilities to regulate 621 pesticides under FIFRA, EPA it needs to determine whether pesticidal products containing 622

an meet the statutory standards for registration. As summarized previously EPA believes that 623
what intentionally-produced nanoscale material materials are in a pesticide product , whether as an 624 active or inert ingredient, meet the statutory standards for registration

. is relevant to that 625
determination. Accordingly, EPA needs is considering how to collect information not only to 626
know about the presence of what nanoscale materials are in pesticide products, but also to have 627
available all other information that may be relevant to the assessment of the potential of such 628 pesticide products to cause unreasonable adverse effects on the environment , and/or . Such 629 information may be important for EPA to determine whether EPA should continue the 630 registration of a product, or ame nd, as appropriate, the terms and conditions of registration of a 631 product. EPA is therefore soliciting public comme nt on two possible approaches for obtaining 632 this information, as discussed in this document. 633

634

IV. Reporting Information Relevant to Assessing the Presence of Nanoscale Materials in 635

a Pesticide Products 636*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 15 of 30 As mentioned above, FIFRA section 6(a)(2) and implementing regulations in 40 CFR 637 part 159 require pesticide registrants to report certain information if that information : 638
639

1 ) I s additional ; 640

641

2 ) Is factual ; and 642

643 3) R egards unreasonable adverse effects on the environment of the pesticide

. Per 40 644 CFR 159.195, this includes information that, if co rrect, a registrant knows, or reasonably should 645 know, would be regarded by EPA, either alone or in conjunction with other information about 646 the pesticide, as raising concerns about the continued registration of a product or about the 647 appropriate terms and conditions of registration of a product. 648
649
Under EPA’s s ection 6(a)(2) regulations, which are codified at 40 CFR Part 159, Subpart 650 D, once the Agency has info rmed registrants that EPA considers a particular type of information 651
relevant to determining whether a pesticide has the potential to cause unreasonable adverse 652 effects on the environment, that type of in formation becomes reportable under FIFRA sec tion 653 6(a )(2). T he failure to report required information, or delays in reporting, are regarded by EPA 654
as violations of FIFRA sec tion 6(a)(2), which in turn makes them subject to enforcement action 655 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. 656 136j(a)(2) (N)

. 657

658 In light of the foregoing and in consideration of the potenti al for nanoscale material to 659 cause different effects and to behave differently in the environment and within organisms from 660 larger particles of the same substance, as well as from nanoscale ma terials with different 661 characteristics (see Unit III.B.), i t is EPA’s position EPA believes that any of the following types 662 of information are relevant to assessing the pote ntial of a pesticide to cause unreasonable adverse 663
effects on the environment and are thus reportable under FIFRA section 6(a)(2) : : 664
665

 any information concerning or indicating the presence of what nanoscale 666
material materials are present in pesticides , whether as an active in gredient or as an inert 667 ingredient; 668

669

 for any pesticide product that contains nanos cale material, whether active or inert, any 670 existing information not previously provided to the Agency that characterizes the size and 671
size distribution of the nanoscale mate rial as measured in nanometers; 672

673

 for any pesticide product that contains nanoscal e materials, whether active or inert, any 674 existing information not previously provided to the Agency that describes the 675 manufacturing process used to produce the nanos cale material in whatever size range it is 676 produced; 677
678

 for any pesticide product that contains nanoscal e materials, whether active or inert, and 679 that also is or will be used for an end-use formulation that contain(s) a composite (e.g., 680 the active ingredient is a matrix complex comprised of the nanoscale material(s) in 681 combination with a carrier, such as silica or sulfur), any existing information not 682*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 16 of 30 previously provided to the Agency that characterizes the size and size distribution of the 683 composite; and 684
685

 for any pesticide product that contains nanoscal e materials, whether active or inert, any 686 existing information not previously provided to the Agency that shows adverse effects at 687 any level of exposure to the nanoscale materi al on humans or nontar get species, and/or 688 that shows the levels or nature (e.g. routes, frequency, or life stage) of potential human 689 and environmental exposure. 690
691 Importantly, the foregoing is not intended to be an exclusive list. To the extent that a 692 registrant has a pesticide product that contains a nanoscale material , and in addition has any other 693 existing information not captured in the previous list above that pertains to, concerns, or 694
otherwise relates to the nanoscale material and has the potential to raise questions about the 695 continued registration of a pr oduct or the appropriate term s and conditions of a product 696 registration, it EPA is EPA’s position that it also considering whether this too must should be 697 submitted to the Agency under FIFRA section 6(a)(2).

. 698

699

In addition, since the types of informati on described above are reportable under 700

FIFRA sec tion 6(a)(2), these types of information also are reportable EPA will review 701 information submitted concerning what nanoscale materials are present, including any existing 702 information not previously provided to the Ag ency on size and size distribution, manufacturing 703 process, and adverse effects. EPA will use this and product use information to determine if it 704 raises any issues, not previously considere d, regarding the product’ s potential to cause 705
unreasonable adverse effects on the environment. In some cases, EPA may determine that 706 additional information is needed to assess such po tential; in this case, additional data may be 707 required including data on physical and chemical pr operties, rate of nanos cale material release, 708 and acute, subchronic, and chronic toxici ty to human and ecological receptors. 709

710 V. Reporting the Presence of Nanoscale Materials in Pesticide Products 711

712
As discussed in Units III and IV of this docum ent, EPA believes that information about what 713 nanoscale materials are in pesticid e products is important to its as sessment of whether pesticides 714 meet the statutory standard for registration. EPA may require such information under either 715 FIFRA section 6(a)(2) or sect ion 3(c)(2)(B). The Agency believes that announcing the 716 applicability of FIFRA section 6(a)(2) to this type of information would be the most efficient and 717 expedient administrative approach to obtaining existing informati on about nanoscale materials in 718 pesticides, in which case any regist rants with this type of informa tion would be required to report 719 it to EPA. The Agency is considering, however, an alternative approach under which it would 720 issue DCIs under FIFRA section 3(c)(2)(B) to obta in this information, in which case registrants 721
that received the DCI would be required to respond. This Un it of the document discusses the 722 two possible approaches and re lated procedures for obtaining information concerning nanoscale 723 materials in pesticides. 724
725

A. FIFRA section 6(a)(2) 726

727 As mentioned previously, FIFRA section 6( a)(2) and implementing regulations in 40 728 CFR part 159 require pesticide registrants to repo rt certain information if that information: 729*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 17 of 30 730 1). Is additional; 731

732 2). Is factual; and 733

734 3). Regards unreasonable adverse effects on the environment of the pesticide. 735

736 Per 40 CFR 159.195, this includes information that, if correct, a re gistrant knows, or 737 reasonably should know, would be regarded by EPA, either alone or in conjunction with other 738 information about the pesticide, as raising con cerns about the continued registration of a product 739 or about the appropriate terms and c onditions of registration of a product. 740

741 Announcing the applicability of FIFRA secti on 6(a)(2) to informa tion about nanoscale 742 materials in pesticides would not mean that EPA is expanding its interpre tation of FIFRA section 743 6(a)(2) or changing its regulations . Rather, consistent with EP A’s section 6(a)(2) regulations, 744 EPA would be merely identifying a set of inform ation that adds to the subset of reportable 745 section 6(a)(2) data explicitly identified at present under the section 6(a)(2) regulations. 746

747 Further, the Agency notes that the identif ication of information as reportable under 748 FIFRA section 6(a)(2) does not mean that any pa rticular pesticide or group of pesticides, to 749 which such information pertains, poses a risk. Rather, the requirement merely indicates that 750 EPA has determined that a particular type of information is relevant to, and may improve the 751 Agency’s ability to assess, whether the pe sticide would cause an unreasonable adverse 752
environmental effect. 753
754 As part of this approach, EPA would also require that a ny such information be reported in 755 connection with any applic ation to register a pes ticide product containing any nanoscale material 756 (40 CFR 152.50(f)(3)). As with the reporting obligation under FIFRA section 6(a)(2), EPA 757 would consider the failure to provide these types of information with an application for a product 758 containing nanoscale material to be a violation of FIFRA sections 12(a)(2)(B)(ii) and 12(a)(2)(N). 759

760 Agency regulations implementing FIFRA sectio n 6(a)(2) provide that a registrant must 761 submit information to EPA that is reportable under section 6(a)(2) no later than the 30 th calendar 762 day after the registrant first possesses or beco mes aware of the information (40 CFR 159.155). 763 In addition, a registrant is required to subm it to EPA any section 6(a)(2) information not 764 explicitly covered under the section 6(a)(2) regu lations if EPA has informed the registrant that 765
such additional information has th e potential to raise questions about the continued registration 766 of a product or the appropriate terms and c onditions of registration of a product (40 CFR 767 159.195). Th e Agency will beg in to apply the interp retation announced herein that pertains to 768
nanoscale materials and FIFRA section 6(a)(2) 9 0 days after publication of this document

. 769 Absent specific , earlier notice to a registrant, therefore, EPA will view that date as the date on 770

w hich a registrant first became aware that such information is reportable under s ection 6(a)(2)

. 771 Thus, absent a specific notice, a registrant will comply with its FIFRA section 6( a)(2) obligations 772
in this area as long as EPA receives the reportable informa tion within 12 0 days after publication 773
of this document

. 774
775*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 18 of 30 Finally, although this announcement currently limits this reporting requirement only to 776
nanoscale materials that ar e “intentionally produced” such that any dimension falls within the 777 specific size range currently under sc rutiny (i.e., between approximately 1 and 100 nanometers)

, 778
it is subject to change in the futu re as new information becomes available that warrants change. 779 Accordingly, the Agency reserves the right to revisit and change th e reporting requirement 780
announced herein if necessary. 781

782
V. After learning that EPA was consideri ng relying on FIFRA 6(a)(2) to require 783 reporting, some stakeholders raised questions ab out the use of FIFRA section 6(a)(2) to obtain 784 this information. Even though, as stated above, EP A is not making a judgment that the presence 785 of any particular nanoscale material poses a ri sk, it has been argued th at use of the “adverse 786 effects” reporting authority in FIFRA sec tion 6(a)(2) could create a “stigma” for the 787 nanotechnology industry. 788
789 EPA does not believe that using FIFRA Sec tion 6(a)(2) to gather information on the 790 presence of nanoscale materials in pesticid e products would create a stigma for the 791 nanotechnology industry. EPA’s l ongstanding interpretation of Secti on 6(a)(2) is that it is not 792 limited to requiring reporti ng only of actual “adverse effects” of pesticides, and its use does not 793 imply that “adverse effects” actually have occurre d, or even could occur, in connection with the 794 pesticide or pesticide ingredient on which the information is being obtained. FIFRA section 795 6(a)(2) requires reporting of “additional factual information regarding unreasonable adverse 796 effects on the environment,” where “unreasonabl e adverse effects on the environment” is 797 specifically defined as a risk/benefit standard. EPA’s implementing regulations require reporting 798 of a wide range of data, which – like informati on on nanoscale materials – are relevant to EPA’s 799 risk/benefit evaluations, but which do not indicate the pesticide cau ses any adverse effects. Any 800 suggestion that this information gathering proposal implied an EPA position on the adverse 801 effects of pesticides containing nanoscale materials would be a mi sinterpretation of EPA’s intent. 802

803 It is further EPA’s position that merely f iling an additional report under FIFRA section 804 6(a)(2) does not stigmatize pestic ides and would not stigmatize a ny nanomaterials in pesticides, 805 since filing such reports is quite common. On average, EPA receiv es 200 studies and 56,000 806 incident reports per year under this authority. In fact, over the last ten year s, pesticide registrants 807 have filed section 6(a)(2) reports on more than tw o-thirds of all pesticide active ingredients. 808
809 Use of FIFRA section 6(a)(2) also would have only a minimal overall administrative 810 burden for both EPA and industry. Under section 6(a)(2), only registrant s who know that their 811 products contain nanoscale materials would be required to report to EPA. Further, they would be 812 required to report only the information they know about. Section 6(a)(2) does not require a 813 registrant to generate new data or to seek out additional information. Further, registrants and 814 applicants whose products do not contain nanosc ale materials (or who do not know that their 815 products contain nanoscale materials) would have no reporting obligation under FIFRA section 816 6(a)(2). Under this approach, EPA would be required to keep track of each response received 817 under 6(a)(2), but would not othe rwise need to prepare or trac k individual requests for the 818
information. 819

820

B. DCIs under FIFRA section 3(c)(2)(B) 821

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

Page 19 of 30 As an alternative to relying on FIFRA sec tion 6(a)(2) to obtain information concerning 823 nanoscale materials in pesticides, EPA is also considering issuing DCIs under FIFRA section 824 3(c)(2)(B). The Agency has au thority under FIFRA section 3(c)(2 )(B) to issue a DCI notice to a 825 pesticide registrant directing them to provide data “required to maintain in effect an existing 826 registration of a pesticid e . . .” The DCI notice is addres sed to an individual registrant, 827 specifically identifies the information or data th at the registrant must provide, prescribes an 828 initial response deadline of 90 days, and, if data are to be generated, it may prescribe a timeframe 829 for generating and providing that data. Under FIFRA, EPA can suspend the registration of a 830 pesticide if the registrant fails to respond to a DCI. 831

832 As part of this alternate a pproach, EPA would also need to require the inclusion of this 833 information with any application for registration of a pesticide pr oduct that contains a nanoscale 834 material. EPA is reviewing whether this coul d be done under existing re gulations or whether 835 EPA would need to amend existing regulations to cl arify that this information is required with 836 any application for registration. As with the reporting obligation under FIFRA section 6(a)(2), 837 EPA would consider the failure to provide these types of information with an application for a 838 product containing nanoscale material to be a vi olation of FIFRA secti ons 12(a)(2)(B)(ii) and 839 12(a)(2)(N). 840
841

842 Since EPA's goal is to identify what nanoscal e materials are contai ned in products (and 843 the products that contain them) and to gather ex isting information not previously provided to 844 assess their safety, the DCI would need to require the kinds of in formation specified in Unit IV 845 of this document. Because such a request is not consistent with the Re-registration or 846 Registration Review programs, the Agency would use the Enforcement and Unanticipated 847 Circumstances category available in the curren tly approved Information Collection Request (73 848 FR 55072). 849
850 Unless a registrant has already disclosed the presence of nanoscale mate rial in all of its 851 products, there curren tly is no way to identify with certain ty what nanoscale materials are in 852 products (and the products that contain them). Th erefore, in order to identify what nanoscale 853 materials are in products, EPA could initially send an individual Enforcement and Unanticipated 854 Circumstances DCI order to each of the 1,716 curr ently registered pestic ide producers. Under 855 this approach each of these pesticide registra nts would then be required to respond within 90 856 days by either providing the requested information about th e nanoscale materials in their 857 product(s) or certifying that their product(s) do no t contain nanoscale materials. In addition to 858 keeping track of each response like under 6(a)(2 ), the approach under 3(c)(2)(B) could require 859 EPA to also prepare and track the issuance of in dividual DCIs for each pesticide registrant, as 860 well as determine and take any necessary en forcement actions for non-responders. EPA notes 861 that only pesticide registrants receive DCIs; EPA would need to employ additional 862 administrative procedures to ensure that ap plicants also provided such information. 863

864 A variation on this approach would be fo r EPA to craft a DCI that would be more 865 targeted and place less burden on industry and the Agency, possibly by not requiring a response 866 from recipients of the DCI who do not have (or who do not know that they have) nanoscale 867 material in their registered pest icide products. The Agency has not used such an approach with 868 any DCI in the past, however, and a number of i ssues, including enforcement, would need to be 869*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 20 of 30 addressed if it were to seek to do so here. EP A could also focus its in itial data gathering on 870 certain classes of pesticides that might be most likely to contain a nanoscale material that EPA 871 would be interested in knowing about. EPA is interested in receiving comments on these 872
variations. 873

874
It is useful to note that while FIFRA sec tion 6(a)(2) can be used to obtain existing 875 information, the DCI approach under FIFRA section 3( c)(2)(B) allows the Ag ency to request that 876 data be generated. If EPA uses FIFRA secti on 6(a)(2) authority and the Agency learns, for 877 instance, the identity of a nanoscale material pres ent in a product, and subsequently determines 878 that sufficient data are not available to support the continued registration of the pesticide, EPA 879 could then use the DCI approach under FIFRA s ection 3(c)(2)(B) to gather such information. 880 EPA must use the DCI approach if EPA intends to require a registrant to provide information 881 which the registrant does not already possess. 882

883 It is anticipated that some registrants w ill request that EPA review information to 884 determine if their product contains nanoscale materi als. To the extent that the description of 885 nanoscale material to a particular product or i ngredient is unclear, EPA will review information 886 concerning the composition and manufacturing pr ocess of the pesticide product and, based on 887 that information, the Agency will determine whether the product does (or does not) contain 888
nanoscale material. 889
890 It has been suggested that th e use of a 3(c)(2)(B) approach would resu lt in submission of 891 information that only reflected the composition of registrants’ products at the time of their 892 responses, but that EPA would need periodically to issue DCIs to insure that registrants did not 893 alter the composition of the produc ts to add nanoscale materials after submitting their responses. 894 EPA is interested in receiving comments on options whereby it can ensure registrants report what 895 nanoscale materials are in products, regardless of when they are added to the pesticide. 896
897 Under either the 6(a)(2 ) or the 3(c)(2)(B) appr oach, DCIs targeted to individual pesticide 898 products that contain specific na noscale materials would likely be used in the future to collect 899 more specific information or data about particul ar products. EPA would consider doing so on a 900 case-by-case basis and would tailor any request for information accordingly. 901
902

C. Amending the Pesticide Data Requirement Regulations 903
904 Some stakeholders have suggest ed, as an alternative to relying on either FIFRA section 905 6(a)(2) or 3(c)(2)(B) DCIs to obtain informa tion concerning nanoscale materials in pesticides, 906 that EPA instead promulgate a regulation ame nding the data requirements in 40 CFR parts 158 907 and 161. The Agency could amend the data requiremen ts to include disclosure of what nanoscale 908 materials are present as part of the pesticide registration process. However, completing this 909 action would not provide information on cu rrently registered pesticide products. 910
911 The Agency sees such proposed rulemaking with a broader scope in that it would address 912 not only the basic informa tion such as identifying what nanos cale materials are in products, but 913 also many other types of data required for maki ng safety evaluations. The Agency is currently 914 making data need decisions on a case-by-case basis, and EPA is trying to ta ilor data requirements 915 to the particular characteris tics of each product. The Agency does not yet have the knowledge 916*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 21 of 30 base typically gained through the registration pro cess to support the develo pment of specific data 917 requirements that would be imposed broadly fo r the registration of pesticides containing 918 nanoscale materials across all the application and use scenarios, as required for such a 919 rulemaking. 920
921 Although it could take considerable time to fi nalize and implement a rule establishing 922 standard data requirements for pesticides contai ning nanoscale materials, and the Agency thus 923 believes that this approach by itself would not ge nerate information on na noscale ingredients in 924 pesticides in a timely manner, EPA al so seeks comment on this approach. 925
926

VI. Proposed Policy Regarding Classification of Applications under FIFRA and PRIA for 927 Products Containing Nanoscale Active and Inert Ingredients 928 Through this document

, EPA also is more bro adly announcing how it propose s to address 929
the status of nano scale materials as new active or inert ingredients for purpose s of both 930
FIFRA and PRIA. As discussed in more detail above 931
As discussed in more detail earlier in this document , under FIFRA, all pesticides must 932 meet stringent statutory and regul atory standards before they ar e registered by the Agency and 933
allowed to be marketed and sold. Pesticides co ntaining nanoscale material s, whether as active or 934 inert ingredients, must meet the same safety stan dards as other pesticides. Because of the large 935 and increasing body of data described in Unit III

. B. of this document dem onstrating that size can 936 alter the manner in which materials behave and, in turn, the potential risk to human health and 937 the environment associated such materials, EPA proposes to apply an initial presumption that 938 active and inert ingredients, wh ich are the nanoscale versions of non-nanoscale active and inert 939 ingredients already presen t in registered pestic ide products, are potentiall y different from those 940 conventionally-sized counterparts. For the same reasons Because the size, shape, and other 941 characteristics of nanoscale ingred ients are likely to vary widely , EPA also proposes to apply an 942 initial presumption that nanoscale active and inert ingredients are potentially different even from 943 other, already-registered nanoscale versions of the same ingredients. As explained below later in 944
this document , however, applicants can overcome this pr esumption on a case-by-case basis. 945
946 Historically, EPA has evaluated an application for registration of a pesticide product that 947 claims to have the same composition and uses as a currently registered pesticide – a so-called 948 “me-too” application – under either the “conditio nal” registration or “unconditional” registration 949 authorities in FIFRA section 3(c )(7) and section 3(c)(5), respec tively. In making the statutory 950 determinations under section 3(c )(7)(A) – whether the applican t’s product is identical or 951 substantially similar to a currently registered pe sticide or differs only in ways that would not 952 significantly increase the risk of unreasonable adverse effects on the environment, and that 953 approving the registration in the manner proposed w ould not significantly increase the risk of 954 any unreasonable adverse effect on the environment – EPA has focused on whether the use 955 patterns of the products are iden tical or similar and whether th e ingredients present in the 956 products have the same chemical structure and ar e present in about the same percentages. Until 957 recently, EPA generally has not focused on the size of an ingredient as an attribute relevant to 958 making the determinations under section 3(c)(7)(A). 959
960
As noted above previously , however, once the size of an ingredient is reduced below 961 approximately 100 nm, a substance can exhibit diffe rent properties, and th erefore it may also 962 have different potential environm ental health and safety proper ties. Accordingly, for a product 963*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 22 of 30 containing an ingredient that is a nanoscale version of a c onventionally-sized active or inert 964 ingredient contained in an al ready- registered product, EPA necessarily will may require 965 adequate additional data in order to determine that the nanoscale material differs only in ways 966 that do not significantly increase the risk of unreasonable advers e effects on the environment and 967 that approving the registration in the manner propos ed would not significan tly increase the risk 968 of any unreasonable adverse effect on the envi ronment, and/or require different terms and 969 conditions for the registration. The implication of this thinking , therefore, is that EPA cannot 970 automatically EPA is thus proposing that it not make the requisite findings absent specific 971
information on the nanoscale material included in a pesticide product when the application relies 972 on a comparison to a currently registered pes ticide product containing either a non-nanoscale 973 version of the same ingredient or another nanosca le version of the ingred ient that has different 974
characteristics. The Under this approach, the Agency w ill would follow the same thinking in 975 making the statutorily required determinations unde r FIFRA section 3(c)(7)(B) and 3(c)(7)(C), as 976 well as FIFRA section 3(c)(5). 977
978 For purposes of registration under FIFRA sec tion 3(c)(5) or 3(c)(7), therefore, EPA 979 would initially classify any app lication for registration of a pest icide product containing an active 980 or inert ingredient that is a nanoscale material as an application for a “new” active or inert 981 ingredient, even when another registered pest icide product contains a non-nanoscale form of the 982 ingredient or a nanoscale form of the ingredie nt with different size dimensions or other 983 properties. This initial presumption, however , could be rebutted on a case-by-case basis through 984 the submission of, among other possi bilities, bridging data or othe r information demonstrating to 985
EPA’s satisfaction that the nanoscale material’s properties, which are re levant to assessing the 986 potential risks to human health a nd the environment, are substantia lly similar to the properties of 987 the already-registered non-nanoscale or already-re gistered nanoscale form of the material, or that 988 the nanoscale material differs only in ways that do not significantly increase the risk of 989 unreasonable adverse effects on the environment, and that approving th e registration in the 990 manner proposed would not significa ntly increase the risk of a ny unreasonable adverse effect on 991
the environment. 992
993 If an applicant can could make this showing to EPA’s sa tisfaction, then the application 994

c w ould be processed as a me-too application w ithin the timeframes prescribed for such 995 applications. However, if an applicant cannot could not make this showing to EPA’s satisfaction, 996 then EPA would process such products as new ac tive ingredients or ne w inert ingredients and 997 would complete its review within the timeframes prescribed for such applications. In those 998 circumstances, the Agency would likely require the applicant to provide the types of data 999 typically required for an assessment of the potenti al hazards and exposure to a new active or inert 1000 ingredient. Under this proposed po licy, it would also follow that if a registrant wished to change 1001 the composition of its product to include a na noscale version of a ma terial that EPA had 1002 previously approved in non-nanoscale form, the registrant would need to notify EPA and obtain 1003 EPA approval before making such a cha nge in the composition of its product. However, as 1004 noted earlier, the registration status of a product would not change merely as a result of 1005 providing information to EPA about the presence of a previously-unreported nanoscale material. 1006 If EPA made an affirmative finding that a change in status or conditions of use was necessary, 1007 EPA would notify the registrant in accordance with applicable regula tions and procedures. 1008
1009*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 23 of 30 VI I . Does This Document Contain Binding Requirements and When Do They Take 1010
Effect ? ? 1011

1012
This document announces how FIFRA section 6(a)(2) applies in a particular circ umstance . This 1013

announcement informs registrants that certain information is re portable pursuant to FIFRA section 6(a)(2) and 40 1014

CFR 159.195

. As such, the document explains the applicability of the stat ute and regulation and makes clear the 1015 requirement al so applies to applicants through 40 CFR 152.50(f)(3)

. As already discussed above, t h e Agency will 1016
begin to apply this interpretation 9 0 days after publication of this document in the Federal Register

. seeks 1017 comments on how the Agency could use FIFRA sec tion 6(a)(2) or FIFRA section 3(c)(2)(B) to 1018 gain information on what nanoscale materials are in pesticides. Given that the Agency is seeking 1019 comment before determining its approach to obt aining information on what nanoscale materials 1020 are in pesticides, there are no bindi ng requirements in this document. 1021

1022
The Once this document is finalized, the Agency’s proposed policy for determining 1023
whether a nanoscale material is a new active or inert ingredient for pur poses of both FIFRA and 1024

PRIA is would be intended only as guidance to EPA personnel and decision-makers and to 1025 pesticide applicants. While the requirements in the statute and Agency regulations are binding 1026 on EPA and the applicants, the proposed policy de scribed in this documen t would not be binding 1027 on EPA personnel, pesticide appl icants, or the pub lic. Accordingly, EPA may depart from the 1028 policy proposed herein if and when circumstances warrant. Likewise, pesticide applicants may 1029 assert that the proposed policy is not applicable to a specific pest icide or situation in which EPA 1030 may be expected to apply it. 1031

1032

VII I . Questions for Comment 1033 Notwithstanding the fact that this document 1034 The Agency is announcing an interpretive rule of general applicability and a separate statement 1035 of general policy, both of which are exempt fr om the notice and comment requirements of the 1036 Administrative Procedure Act, EPA is invit ing seeking public comment

. 1037

1038

With respect to the interpretation, EPA is not seeking comment on several questions, including 1039
whether information concerning the pres ence of a nanoscale material in a pesticide product is or it should be 1040

reportable under use the FIFRA section 6(a)(2 ), but we are interested ) reporting obligation to obtain 1041
information on what nanoscale material are in pesticide products or use FIFRA section 1042 3(c)(2)(B) as described in comment on the cla rity of the interpretation and whether the this document to 1043
obtain such information. 1044
1045 With respect to the scope of reportable information should be expanded. EPA 1046 specifically invites comments on the following issues: 1047

1048

1. In view of the Agency’s goa l of identifying what nanoscale materials are in products so 1049
that EPA can determine whether it needs addi tional data to evaluate the products’ safety 1050 under FIFRA, should EPA change the descri ption of a “nanoscale material”? For 1051 example, should the size range remain “bet ween approximately 1 and 100 nm in one 1052
dimension”? Are there other characteristics that EPA should consider, e.g., morphology, 1053 including shape and crystal structure; su rface chemistry and reactivity; specific surface 1054 area, charge; solubility ; conductive, magnetic, and optical properties? 1055
1056*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 24 of 30 1. 2. Should the reporting requirement apply only to nanoscale material that is “intentionally 1057 produced to have at least one dimension that measures between approximately 1 and 100 1058 nanometers,” or should it al so apply to naturally occu rring materials? Why? 1059

1060

3. Is the meaning of “intentionally produced ” sufficiently clear? If not, in what 1061
circumstances would the term be unclear and how might it be clarif ied? Would offering 1062 a consultation procedure – by which a regist rant or applicant de scribes to EPA the 1063 production process that results in the presence of a material in the nanoscale size range, 1064 and EPA responds with a determination regardin g whether reporting is required – be an 1065 acceptable approach to providing clarity? 1066

1067

2. 4. Should the reporting requirement apply to ingr edients in pesticides that contain any 1068 amount of a nanoscale material, or should the requirement apply only if an ingredient 1069 contains more than a specified percentage (e .g., 10%) of nanoscale materi al? If the latter, 1070 what should the specified pe rcentage be and why? 1071

1072

3. 5. How should the reporting requirement apply to a pesticide manufacturer who purchases 1073 ingredients that may cont ain nanoscale material? 1074
1075

6. Are there ways in which the description of “nanoscale materials” can be refined and 1076 clarified, including ways in which agglomerati on and aggregation could be considered as 1077 well as suggestions for ways in which more su bjective criteria, such as “unique or novel 1078 properties” can be incorporated into the screening criteria? 1079

7. Is EPA’s description of “na noscale material” inconsistent with other definitions of 1080
nanoscale material or similar terms? If s o, please comment on whether such differences 1081 create any regulatory issues. In particul ar, does the focus on “intentionally produced” 1082 materials create any such inconsistency with other definitions of nanoscale materials or 1083
similar terms? 1084
1085

8. If a pesticide is identified as containing a particular nanosca le material, what would be 1086 the most useful next steps to inform EPA’ s understanding of potential risks associated 1087 with the pesticide? Are there tests that could provide useful information toward an 1088 understanding of risk that woul d be common to all nanoscale ma terials, or should the data 1089 requirements necessarily be compound- and situation- specific? How should 1090 bioavailability be considered in determini ng testing requirements (e.g., are nano-particles 1091 respirable or bound to other components)? 1092
1093 With respect to the proposed policy approaches , EPA is seeking comment on how to 1094 implement it them to ensure efficient, effective, an d timely review of applications. EPA 1095 specifically invites comments on the following issues: 1096
1097

1. Is there a way to determine, in advance of receiving an application for registration of a 1098 product containing a nanoscale material, whethe r a particular kind of nanoscale material 1099 has properties that, for purposes of risk asse ssment, are essentially the same as larger 1100
sized materials of the same substance? If so, how would such determinations be made 1101 and on what would they be based? 1102*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 25 of 30 1103

2. What kinds of information should EPA accept as demonstrating that a pesticide product 1104 containing a nanoscale ingredient is identical or substantially similar to a currently 1105 registered pesticide or differs only in ways that would not significantly increase the risk 1106
of unreasonable adverse effects on the environm ent, and that approving the registration in 1107 the manner proposed would not significantl y increase the risk of any unreasonable 1108
adverse effect on the environment? 1109

1110

3. Can you suggest any alternative(s) to the proposed policy approaches that would be 1111 equally or even more effective in addressi ng the status of nanos cale materials as new 1112 active or inert ingredients for purposes of both FIFRA and PRIA, keeping in mind the 1113 growing body of data showing that size, especially when reduced below approximately 1114 100 nm, may alter the manner in which materials behave and, in turn, the potential risk to 1115
human health and the environment a ssociated with such materials? 1116
1117

VI I I. With respect to the potential alternative ways of obtaining the needed information 1118 on what nanoscale materials are in pesticide prod ucts, EPA specifically invites comments on the 1119 following issues: 1120

1121

1. Has EPA appropriately characterized in this document the current scientific 1122 understanding of the potential risks of nanoscale materials? If not, please comment on 1123 how to characterize the potenti al risks of nanoscale material s. How would the perception 1124
of the risks of nanoscale materials differ depending on the approach used by EPA to 1125 require needed data on nanoscale materials in pesticide? How could EPA lessen the 1126 possibility that issuance of a final requirement to report what nanoscale materials are in 1127 pesticides will result in a public mis understanding of the potential risks of 1128 nanotechnology more generally? 1129

1130

2. Do commenters believe that identificati on of the nanoscale mate rials in pesticide 1131 products is relevant to EP A’s statutory determination regarding the potential for 1132
unreasonable adverse effects on the environment? Please provide the scientific or legal 1133 basis for your view. 1134
1135
3. Has EPA characterized the alternative approaches with respect to which they would: a) 1136 result in a misunderstanding of the potential risks posed by nanoscale materials; b) result 1137 in the timely submission of needed informa tion; and c) impose burdens on pesticide 1138 companies, those whose products do, and do not , contain nanoscale materials? If not, 1139 please comment on those issues. 1140

1141

4. If EPA uses FIFRA section 6(a)(2) to obtain the needed information on nanoscale 1142 materials in pesticides, how could the Agency ensure that its action is not 1143
mischaracterized or misunderstood as a determin ation that the mere f act that a pesticide 1144
contains nanoscale materials causes unr easonable adverse environmental effects? 1145

1146
5. If EPA were to use DCIs to obtain the n eeded information on nanoscale materials in 1147 pesticides, how could EPA reduce both the bu rdens on registrants and on EPA, as well as 1148 the time required to complete such a process? For example, is it possible to reduce the 1149*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 26 of 30 burdens on registrants by targe ting only certain types of pr oducts? If so, how would EPA 1150 determine which products should receive DCIs? 1151

1152

6. What are the advantages and disadvantag es of requesting information on nanoscale 1153 materials specifically versus requesting information on size di stribution generally? (Note 1154 that either type of information could be collected under either the 6(a)(2) or the 1155 3(c)(2)(B) approach, except that 6(a)(2) canno t be used to require the production of new 1156 information that does not already exist, wh ile a collection under 3(c)(2)(B) must be 1157
directed to an individual registrant and requires a res ponse.) Is identifying what 1158 nanoscale materials are in products a useful first step, or should EPA move towards 1159 immediate collection of more specific informa tion, such as particle size distribution, on 1160 products that might contain nanoscale mate rials? Are there ot her physical and/or 1161 chemical properties that might be equally or more important for assessing the potential of 1162 a pesticide to cause unreasonable adverse effects on the environment (e.g., morphology, 1163 including shape and crystal structure; surf ace chemistry and reactivity; specific surface 1164 area, charge; solubility; conductive, magnetic, and optic al properties)? Should 1165 information on these properties be separately requested? What would be the value and 1166 burden of obtaining such information? 1167

7. If EPA were to use rulemaking to establish data requirements for pesticides containing 1168 nanoscale materials, what types of informa tion should EPA use to determine appropriate 1169 data requirements? What types of studies should EPA require to evaluate a nanoscale 1170
material? 1171

1172

8. When choosing an approach for obtaini ng needed data, how should EPA weigh 1173 considerations relating to the need to update its safety eval uations of currently marketed 1174 pesticides in a timely manner, th e goal of ensuring marketpla ce equity, and the interest in 1175 minimizing the burdens on regulated entities? 1176

1177

IX. References 1178
1179
As indicated under ADDRESSES , a docket has been established for this document under 1180 docket ID number EPA-HQ-OPP-2010-0197. The follo wing is a listing of the documents that 1181 are specifically referenced in this document. The docket includes these documents and other 1182 information considered by EPA, including documen ts that are referenced within the documents 1183 that are included in the docket, ev en if the referenced document is not physically located in the 1184 docket. For assistance in locating these other do cuments, please consul t the technical contact 1185
listed under FOR FURTHER INFORMATION CONTACT

. 1186

1187

1. Oberdörster, G. et al., 2005. Nanotoxicology: an emerging discipline evolving from 1188 studies of ultrafine partic les. Environmental Health Perspectives. (113): 823-839. 1189
1190

1. 2. National Nanotechnology Initia tive. 2004. Strategic Plan. 1191 http://www.nano.gov/NNI_Strategic_Plan_2004.pdf

. 1192

C heng et al. 2007

. Effect of carbon nanotubes on developing zebrafish ( Danio rerio ) 1193 embryos. Environ

. Toxicol

. Chem

. 26:708

– 716. 1194*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 27 of 30 2. 3. Department of Health and Human Services. Centers for Disease Control and Prevention. 1195 National Institute for Occupational Safety and Health. Approaches to Safe 1196 Nanotechnology: Managing the Health and Safety Concerns Associated with Engineered 1197
Nanomaterials. November 2009. http://www.cdc.gov/niosh/docs/2009-125/pdfs/2009- 1198 125.pdf (November 2009)

. . 1199

1200

3. Donaldson

, K

. et al., 2000. Ultrafine Particles: Mech anisms of Lung Injury. Philosophical 1201
Transactions: Math ematical, Physical and Engine ering Sciences. 358 (1775): 2741

- 2749

. 1202

1203

4. Donaldson

, K

. et al., 200 2

. Inflammation Caused by Particles and Fibers. Inhalation 1204 Toxicology. 14 (1): 5

- 27

. 1205

1206
5. Duffin

, R

. et al., 2002. The Importance of Surface Ar ea and Specific Reactivity in the 1207 Acute Pulmonary Inflammatory Response to Part icles. Annals of Occupational Hygiene. 1208 46 (1): 242

- 245. 1209

1210

6. Federici et al. 2007, Toxicity of titanium dioxide to rainbow trout ( Oncorhynchus 1211 mykiss ): Gill injury, oxidative stress, and other physiological effects. Aquat

. Toxicol

. 84: 1212
415

– 430. 1213

1214

7. FIFRA Science Advisory Panel (SAP). 2010. “ Evaluation of Hazard and Exposure 1215
Associated with Nanosilver and Ot her Nanometal Pesticide Products. ” Report from the 1216 FIFRA Scientific Advisory Panel Meeting of November, 2009. FIFRA Scientific 1217 Advisory Panel, Office of Science Coor dination and Policy, Office of Prevention, 1218 Pesticides and Toxic Substances, U.S. Environmental Protection Agency. Washin gton, 1219
DC. Available: http://www.epa.gov/scipoly/sap/2009

. 1220

1221

8. 1. Handy et al. 2008, The ecotoxicology and chemistry of manufactured nanoparticles. 2008. 1222 Ecotoxicology 17:287

- 314. 1223

9. 1. Kashiwada et al. 2006

. Distribution of nanoparticles in the see

- through Medaka ( Oryzias 1224 latipes ). Environ

. Health Perspect

. 114: 1697

– 1702

. 1225

1226

10. Kim, Y.S. et al., 2008. Twenty

- Eight Day Oral Toxicit y, Genotoxicity, and Gender

1227
Related Tissue Distribution of Silver Nanoparticles in Sprague

- Dawley Rats. Inhalation 1228 Toxicology. 20 (6): 575

- 583. Klaine et al. 2008

. Nanomaterials in the Environment: 1229 Behavior, Fate, Bioavailabil ity, and Effects. Environ

. .Toxicol

. .Chem

. . 27: 1825

- 1851

. 1230

1231

11. 1. Lovern and Klaper 2006

. Daphnia magna mortality when exposed to titanium 1232 nanoparticles and fullerene (C60) nanoparticl es. Environ

. Toxicol

. Chem

. 25: 1132

– 1137

. 1233

1234

12. 1. National Nanotechnology Initia tive. 2004. Strategic Plan. 1235 http://www.nano.gov/NNI_Strategic_Plan_2004.pdf

. Oberdörster, G. et al., 2005. 1236 Nanotoxicology: an emerging disc ipline evolving from studies of ultrafine particles. 1237 Environmental Health Perspectives

. (11 3): 823

- 839. 1238
1239*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 28 of 30 13. 1. Oberdorster et al. 2006 . Ecotoxicology of carbon

- based engineered nanoparticles: 1240 effects of fullerene (C

- 60) on aquatic organi sms. Carbon 44: 1112

- 1120. 1241

1242

14. 1. Roberts et al. 2007. In vivo biomodification of lip idcoated carbon nanotubes by 1243 Daphnia magna . Environ

. Sci

. Technol

. 41: 3025

– 3029 1244
1245
15. 4. SCENIHR, 2009. Risk Assessment of Pr oducts of Nanotechnologies. European 1246
Commission. Directorate-General for Health and Consumers. Scientific Committee on 1247 Emerging and Newly Identified Risks, Brussels: 28 th Plenary Meeting. January 19, 2009. 1248 http://ec.europa.eu/health/ph_risk/committees/04_scenihr/docs/scenihr_s_01.pdf

. 1249
1250

16. 5. Seaton, A. et al., 2009. Nanoparticles, human health hazard and regulation. 1251 Journal of the Royal Society , published online at: . August 31, 2009. 1252 http://rsif.royalsoc ietypublishing.org/content/early /2009/08/31/rsif .2009.0252.focus.full# 1253 ref-14

. 1254
1255

6. Wick, P. et al., U.S. Department of Health and Human Services, Nati onal Institutes of 1256
Health. 2009. http://ehp.niehs.nih. gov/members/2009/0901200/0901200.pdf

. 1257
1258

17. 7. Kim, Y.S. et al., 2008. Twenty-Eight Day Oral Toxicity, Genotoxicity, and 1259
Gender-Related Tissue Distribution of Silv er Nanoparticles in Sprague-Dawley Rats. 1260 Inhalation Toxicology. 20 (6): 575-583. 1261

8. Handy et al. 2008, The ecotoxicology and chemistry of manufactured na noparticles. 2008. 1262 Ecotoxicology 17:287-314. 1263

9. Klaine et al. 2008. Nanomaterials in the Environmen t: Behavior, Fate, Bioavailability, 1264
and Effects. Environ. Toxicol. Chem. 27: 1825-1851. 1265

1266

18. 10. Federici et al. 2007, Toxicity of tita nium dioxide to rainbow trout ( Oncorhynchus 1267 mykiss ): Gill injury, oxidative stre ss, and other physiological e ffects. Aquat. Toxicol. 84: 1268
415–430. 1269

19. 11. Smith et al. 2007. Toxicity of single walled carbon nanotubes on rainbow trout 1270 (Oncorhyncos mykiss): Respiratory toxicity, organ pathologies, and other physiological 1271 effects. Aquat. Toxicol. 84: 415–430. 1272

12. Lovern and Klaper 2006. Daphnia magna mo rtality when exposed to titanium 1273 nanoparticles and fullerene (C60) nanopart icles. Environ. Toxicol. Chem. 25: 1132–1137. 1274
1275

13. Oberdorster et al. 2006. Ecot oxicology of carbon-based engi neered nanoparticles: 1276 effects of fullerene (C-60) on a quatic organisms. Carbon 44: 1112-1120. 1277

1278

14. Roberts et al. 2007. In vivo biomodificat ion of lipidcoated carbon nanotubes by Daphnia 1279

magna . Environ. Sci. Technol. 41: 3025–3029 1280

1281
15. Kashiwada et al. 2006. Distribution of na noparticles in the see-through Medaka ( Oryzias 1282 latipes ). Environ. Health Perspect. 114: 1697–1702. 1283*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 29 of 30 1284

16. Cheng et al. 2007. Effect of carbon nanotubes on developing zebrafish ( Danio rerio ) 1285 embryos. Environ. Toxicol. Chem. 26:708–716. 1286

1287

17. Kahru and Dubourguier 2010. Review: From ecotoxicology to nanoecotoxicology. 1288 Toxicology 269:105-119. 1289
1290

20. 18. FIFRA Science Advisory Panel (SAP). 2010. “Evaluation of Hazard and 1291 Exposure Associated with Nanosilver a nd Other Nanometal Pesticide Products.” Report 1292 from the FIFRA Scientific Advisory Panel Meeting of November, 2009. Wick

, P. et al., 1293 U.S. Department of Health and Human S ervices, National Institutes of Health. 1294 http:// ehp.niehs.nih www.epa .gov/ members scipoly/sap /2009 /0901200/0901200.pdf

. 1295
1296

VI I I X . Applicable Statutory and Executive Order Reviews 1297

EPA submitted this document to the Office of Management and Budget (OMB) for 1298 review under Executive Order 12866, entitled Regulatory Planning and Review (58 FR 51735, 1299 October 4, 1993). Any changes made in re sponse to OMB recommendations have been 1300
documented in the docket for this action as required by section 6(a) (3)(E) of the Executive Order. 1301

The information collection requirements asso ciated with reporti ng under FIFRA section 1302 6(a)(2) as prescribed in 40 CFR part 159, subpart D are approved under the Paperwork 1303 Reduction Act (PRA), 44 U.S.C. 3501 et seq. The approval is identified under OMB Control No. 1304
2070-0039 and EPA ICR No. 1204. The information collection requirements associated with 1305 DCIs is approved under OMB Control No. 2070- 0174 and identified by EPA ICR No. 2288. If 1306 EPA were to finalize a policy th at required additional reporting of information not currently 1307 collected, or that substantively changed the burde n for such reporting (for example if it resulted 1308 in a larger number of such reports than covere d in current burden estimates), EPA would submit 1309 a request for revised PRA approval to OMB. 1310

The various other statutory a nd Executive Order review re quirements that apply to a 1311 regulatory action do not apply to th is action because this document is not a regulatory action and 1312 does not otherwise impose new requirements. As indicated previously this document clarifies 1313 the applicability of the statute and existing regulation regarding reporting under FIFRA section 1314 6(a)(2) requests comment on several approaches for applying existing requirements in order to 1315
obtain information on nanoscale ma terials in pesticide products and presents the Agency’s 1316 proposed policy for determining whether a nanoscale material is a new active or inert ingredient 1317 for purposes of both FIFRA and PRIA. 1318

List of Subjects 1319

Environmental protection, administrativ e practice and procedure, pesticides, 1320 nanotechnology. 1321

1322 Dated: ________ 1323*** Interagency EO 12866 Review Dr aft – Deliberative – Do Not Cite, Qu ote or Release During Review ***

Page 30 of 30 ________________ 1324 Assistant Administrator for Chemical Safety and Pollution Prevention. 1325

[FR Doc. 10–???? Filed ??–??–10; 8:45 am] 1326
BILLING CODE 6560

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– S 1327