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Page 1 of 31 EP A

- HSRB

- 10

- 02 1 2 Paul Anastas, PhD 3 EP A Science Advisor 4 Of fice of the Science Advisor 5 1200 Pennsylvania Av enue, NW 6 Wa shington, DC 20460 7 8 Subject: October 27

- 28, 2010 EP A Human Studies Review Board Meeting Report 9 10 Dear Dr

. Anastas, 11 12 The United States Enviro nmental Protection Agency (EP A or Agency) requested that the 13 Human Studies Review Board (HSRB) provide scientific and ethics reviews of two new and one 14 revised protocols for studies involving intentional exposure of human subjects to pesticides: a 15 proposed Carroll

- Lo ye Biological Research, Inc. (CLBR) insect repellent ef ficacy study (No 16 Mas

- 003); a proposed Agricultural Handler Exposure Ta sk Force, LLC (AHETF) scenario 17 measuring dermal and inhalation exposure by pesticide applicators who use backpack spray e rs or 18 hand gun spray ers in utility rights

- of

- way (AHE

- 400); and a revised AHETF water

- soluble 19 packaging mixing and loading scenario and protocol (AHE

- 120) previously reviewed by

the 20 HSRB in June 2009. 21 22 The Agency also requested that the HSRB review a comp leted study of dermal and 23 inhalation exposure of professional janitorial workers who clean floors with an antimicrobial 24 pesticide product using a mop and bucket, conducted by the Antimicrobial Exposure Assessment 25 Ta sk Force II (AEA TF II). This study

(AEA

- 0 3) was conducted after publication of the EP A’ s 26 expanded final rule for protection of subjects in human research (40 CFR 26) on February 6, 27 2006 (71 Federal Register 24, 6137). The data will be posted to the Biocide Handlers Exposure 28 Database (BHED®), and used genericall y to estimate dail y dermal and inhalation exposures of 29 those who clean floors with antimicrobial pesticides using a mop and pail. 30 31 The enclosed report provides the Board’ s response to EP A charge questions presented at 32 the October 27

- 28, 2 010 meeting. 33 34 Assessment of Proposed Carroll

- Lo ye Biological Research Study No Mas

- 003: Field Ef ficacy 35 Te st of 16% Para

- menthane

- 3,8

- diol (PMD) and 2% Lemongrass Oil Based Repellent ‘No Mas’ 36 Against Mosquitoes. 37 38 Science 39 40

• The Board concluded that the protoc ol for the proposed field repellency study , if 41 modified in accordance with Agency and HSRB recommendations and conducted 42 accordingl y, is likely to generate scientifically reliable data, useful for assessing the 43 efficac y of the tested material in repelling mosquitoes. 44 45Final Draft Document Dated December 8, 2010

Page 2 of 31 Ethics 46 47

• The Board concluded that the protocol submitted for review , if modified in accordance 48 with Agency and HSRB recommendations and conducted accordingly , is likely to meet 49 the applicable requirements of 40 CFR 26, subparts K and L

. 50 51 Assess ment of Proposed AHETF Scenario and Protocol AHE

- 400: Backpack and Handgun Ap52 plication of L iquid Sprays in Utility Rights

- of

- Way. 53 54 Science 55 56

• The Board concluded the proposed backpack and handgun application scenario, if revised 57 as suggested and performed as described, is likely to generate scientificall y reliable data 58 that may

be useful for assessing the exposure of workers who appl y pesticides in utility 59 rights

- of

- way using backpack or handgun spray ers. 60 61 Ethics 62 63

• The Board concluded that the protocol submitt ed for review, if modified in accordance 64 with Agency and HSRB recommendations and conducted accordingly , is likely to meet 65 the applicable requirements of 40 CFR 26, subparts K and L

. 66 67 Assessment of Revised AHETF Scenario and Protocol AHE

- 120: Water

- Soluble Packaging Mi x68 ing and Loading. 69 70 Science 71 72

• The Board concluded the submitted protocol, if revised as suggested and performed as 73 described, is likel y to generate scientificall y reliable data that may be useful for assessing 74 the exposure of workers who mix and load pesticides in water

- soluble packaging. 75 76 Ethics 77 78

• The Board concluded that the protocol submitted for review , if modified in accordance 79 with Agency and HSRB recommendations and conducted accordingly , is likely to meet 80 the applicable requirements of 40 CFR 26, subparts K and L

. 81 82 Assessment of Completed AEA TF II Research Study AEA

- 03: A Stud y for Measurement of P o83 tential Dermal and Inhalation Exposure during Application of a Liquid Antimicrobial Pesticide 84 Product Using Bucket and Mop Equipment for Cleanin g Indoor Surfaces (MRID 48210201, 85 MRID 48231201, MRID 48231901). 86 87 Science 88 89

• The Board concurred with the Agency ’s assessment that the research reported in the 90 completed AEA

- 03 study report and associated supplemental documents was conducted 91

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Final Draft Document Dated December 8, 2010

Page 3 of 31 in a manner that was reasonably faithful to the design and objectives of the protocol and 92 governing documents of AEA TF

- II. 93 94

• The Board concluded that the Agency has adequately

, if not completely

, considered the 95 limitations on these data that should be considered when usin g the data in estimating 96 exposure of those who apply antimicrobial floor

- cleaning products with mop and bucket. 97 98 Ethics 99 100

• The Board concurred with the Agency ’s assessment that the study submitted for review 101 was conducted in substantial compliance with subparts K and L of 40 CFR 26. 102 103

• In response to a request from the study sponsor for guidance on how to provide 104 individual exposure data to participants once the study is complete, the Board elected to 105 establish a working group that could draft proposed guidance for the Agency and 106 sponsors, which would be reviewed b y the full Board during a future HSRB meeting. 107 108 109 Sincerely

, 110 111

112 113 Sean Philpott, PhD, MSBioethics 114 Chair 115 EP A Human Studies Revi ew Board 116Final Draft Document Dated December 8, 2010

Page 4 of 31 NOTICE 117 118 This report has been written as part of the activities of the EP A Human Studies Review 119 Board, a Federal advisory committee providing advice, information and recommendations on 120 issues related to scientific and ethical aspects of human subjects research. This report has not 121 been reviewed for approval by the Agency and, hence, the contents of this report do not 122 necessarily

represent the view and policies of the Environmental Protection Agency , nor of other 123 agencies in the Executive Branch of the Federal government, nor does the mention of trade 124 names or commercial products constitute a recommendation for use. Yo u may obtain further 125 information about the EP A Human Studies Review Board from its website at 126 http://www.epa.gov/osa/hsrb

. Yo u may also contact the HSRB Designated Federal Of ficer, via e

127 mail at ord

- osa - hsrb @epa.gov 128 129 In preparing this document, the Board carefull y considered all information provided and 130 presented b y the Agency presenters, as well as information presented by public commenters. 131 This document addresses the information provided and presented within the structure of the 132 charge b y the Agency

. 133

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Final Draft Document Dated December 8, 2010

Page 5 of 31 US ENVIRONMENT AL PROTECTION AGENCY 134 HUMAN STUDIES REVIEW BOARD 135 136 Chair 137 138 Sean Philpott, PhD, MSBioethics, Director for Res earch Ethics, The Bioethics Program of Union 139 Graduate College and the Mount Sinai School of Medicine, Schenectady, NY 140 141 Vi ce Chair 142 143 Janice Chambers, PhD, DABT, Fellow AT S, Wi lliam L . Giles Distinguished Professor, Director, 144 Center for Environmental Health S ciences, College of V eterinary Medicine, Mississippi S tate 145 University

, Mississippi S tate, MS 146 147 Members 148 149 George Fernandez, PhD, Professor of Applied Statistics, Director of the University of Nevada

150 Reno Center for Research Design and Anal ys is, University of Nevada

- Reno, Reno, NV 151 152 Vanessa Northington Gamble, MD, PhD, University Professor of Medical Humanities, Professor 153 of Health Policy

and American Studies, The George W ashington University

, Wa shington, DC 154 155 Sidney

Green, Jr., PhD, Fellow of the AT S, Professor, Department of Pharmacology , Howard 156 University

College of Medicine, W

ashington, DC 157 158 Dallas E. Johnson, PhD, Professor Emeritus, Department of Statistics, Kansas State University , 159 Manhattan, KS 160 161 Michael D. Lebowitz, PhD, FCCP , Retired Professor of Public He alth & Medicine, Universit y of 162 Arizona, T

ucson, AZ 163 164 Jose E. Manautou, PhD, Associate Professor of T oxicology , Department of Pharmaceutical 165 Science, University of Connecticut School of Pharmacy , Storrs, CT 166 167 Jerry

A . Menikoff, MD, JD, Director, Of fice for H uman Subjects Research, Of fice of the 168 Secretary

, Department of Health and Human Services, Rockville, MD 169 170 Rebecca Parkin, PhD, MPH, Professorial Lecturer (EOH) Human Risk Assessment, School of 171 Public Health and Human Services, The George W ashington Universi ty

, W ashington, DC 172 173 Wi lliam Popendorf, PhD, MPH, Professor Emeritus, Department of Biology , Utah State 174 University

, Logan, UT 175 176 Vi rginia Ashb y Sharpe, PhD, Medical Ethicist, National Center for Ethics in Health Care, 177 Ve terans Health Administration, Wa shington, DC 178 179Final Draft Document Dated December 8, 2010

Page 6 of 31 Linda J. Yo ung, PhD, Professor, Department of Statistics, Institute of Food and Agricultural 180 Sciences, University of Florida, Gainesville, FL 181 182 Human Studies Review Board Staf f 183 184 Jim Downing, Executive Director, Human Studies Review Board Staff, Of fice of the Science 185 Advisor, United States Environmental Protection Agency , W ashington, DC 186

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Final Draft Document Dated December 8, 2010

Page 7 of 31 INTRODUCTION 187 188 On October 27

- 28, 2010, the United States Environmental Protection Agency ’s (EP A or 189 Agency) Human Studies Review Board (HSRB) met to address scientifi c and ethical issues 190 concerning two new protocols and one revised protocol for research involving human 191 participants: one new study measuring the ef

ficacy of an insect repellent containing para

192 menthane

- 3,8

- diol (PMD) and lemongrass oil against mosquitoes under field conditions; one 193 new study

measuring levels of exposure received by agricultural handlers when appl yi ng 194 commerciall y - available pesticides using backpack spray ers or hand gun spray ers in utility rights

195 of

- way , and a revised study

measuring levels of exposure received by agricultural handlers when 196 mixing and loading pesticides using water

- soluble packaging under various conditions. In 197 accordance with 40 CFR 26.1601, EP A sought HSRB review of these three proposed protocols. 198 Each of these protocols i s discussed more full y below

. 199 200 In addition, the Agency has data from one completed study measuring levels of exposure 201 received b y janitorial workers when appl yi ng a commercially

- available antimicrobial pesticide 202 using a mop and bucket. In accordance with 4 0 CFR 26.1602, EP A sought HSRB review of this 203 completed study

. This completed study is discussed more fully below

. 204 205 REVIEW

PROCESS 206 207 On October 27

- 28, 2010, the Board conducted a public face

- to

- face meeting in Arlington, 208 Vi rginia. Advance notice of the meet ing was published in the Federal Register as “Human 209 Studies Review Board; Notice of Public Meeting” (75 Federal Register 193, 61748). 210 211 Following welcoming remarks from Agency of ficials, the Board heard presentations from 212 EP

A on the following topics: one ne w study protocol to measure the ef ficacy of an insect 213 repellent containing PMD and lemongrass oil against mosquitoes under field conditions; one new 214 study

protocol for measuring levels of exposure received b y agricultural handlers when appl yi ng 215 commerciall y available pesticides using backpack spray ers or hand gun spray ers in utility rights

216 of

- way , and a revised study

protocol measuring levels of exposure received by agricultural 217 handlers when mixing and loading pesticides using water

- soluble packaging under various 218 conditions. In addition, a completed study for the measurement of potential dermal and 219 inhalation exposure during application of a liquid antimicrobial pesticide product using a bucket 220 and mop was reviewed. 221 222 The Board also asked clarifying questio ns of several study sponsors and/or research 223 investigators, including: 224 225 Dr. V

ictor Cañez, Te chnical Chair, Agricultural Handler Exposure Ta sk Force 226 Dr. Scott Carroll, Study Director, Carroll

- Lo ye Biological Research 227 Mr. Shawn King, Director of Operations, Carroll

- Lo ye Biological Research 228 Mr. Robert Roogow, Chief Operations Officer, Independent Institutional Review Board, 229 In c. 230 Dr. Sami Selim, Study Director, Selim & Associates 231 232Final Draft Document Dated December 8, 2010

Page 8 of 31 Public oral comments were provided b y: 233 234 Dr. V

ictor Cañez, Te chnical Chair, Agri cultural Handler Exposure T ask Force 235 Dr. Scott Carroll, Principal, Carroll

- Lo ye Biological Research 236 Dr. Hasmukh Shah, Manager, AEA TF 237 238 No written public comments were submitted. 239 240 For their deliberations, the Board considered the materials presented at the m eeting, oral 241 comments, and Agency background documents (e.g., published literature, sponsor and 242 investigator research reports, study protocols, data evaluation records, and Agency science and 243 ethics reviews of proposed protocols and completed studies). A c omprehensive list of 244 background documents is available online at http://www.regulations.gov

. 245 246 CHARGE TO THE BOARD AND BOARD RESPONSE 247 248 Assessment of Pr oposed Carr oll

- Loye Biological Research Study No Mas

- 003: Field 249 Efficacy Te st of 16% Para

- menthane

- 3,8

- di ol (PMD) and 2% Lemongrass Oil Based 250 Repellent ‘No Mas’A gainst Mosquitoes. 251 252 Overview of the Study 253 254 This protocol describes a study to test the repellent ef

ficacy of a lotion formulation co n255 taining 16% PMD and 2% lemongrass oil (‘No Mas’) against three sp ecies of mosquitoes in the 256 field. As submitted to the EP A, the proposed study consists of two interdependent anal ys es: 1) a 257 dosimetry

study designed to determine the amount of lotion that ty pical users would ty

pically 258 apply ; and 2) an ef ficacy study design ed to measure the effectiveness of the compound as a r e259 pellent for those species of mosquitoes likely to be vectors for W

est Nile V irus (WNV) in the 260 United States. 261 262 Dosimetry will be determined by

direct measurement of compound application. The ef fi263 cacy

o f the formulation as a mosquito repellent will be determined by measuring the ability

of 264 the formulations to prevent mosquito landings under field conditions at test sites in California’ s 265 Central V

alley . The ef ficacy study endpoint will be the “Landing with Intent to Bite” (LIBe), and 266 the criterion for data to calculate complete protection time will be the first confirmed LIBe. 267 268 Science 269 270 Charge to the Board 271 272 If the proposed field repellency study protocol No Mas

- 003 is revised as suggested in 273 EP

A’ s review and if the research is performed as described, is the research likely to generate 274 scientifically

reliable data, useful for assessing the efficacy of the tested material in repelling 275 mosquitoes? 276 277

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Final Draft Document Dated December 8, 2010

Page 9 of 31 Board Response to the Charge 278 279 HSRB Recommendation 280 281 The Board concurred with the Agency ’s assessment that the proposed field repellency 282 study

protocol No Mas

- 003, if revised as suggested in EP A’ s review (Fuentes and Sherman 2010) 283 and performed as described, is likely to generate scientificall y reliable data, usefu l for assessing 284 the ef

ficacy of the tested material in repelling mosquitoes. 285 286 HSRB Detailed Recommendations and Rationale 287 288 Protocol No Mas

- 003 from Carroll

- Lo ye Biological Research (Carroll 2010) will be 289 conducted using methods similar to those presented to and commented on by the Board in the 290 past. Apart from the new test material, the proposal is generall y similar to previous Carroll

- Lo ye 291 field studies reviewed b y the Board. 292 293 The study protocol was relatively

clear and addressed adequately a number of key 294 scientific issues, including: scientific justification, objectives, and data collection and 295 compilation methods. The Board concurred with the Agency ’s assessment that the proposed field 296 repellency

study protocol No Mas

- 003 is likely to generate scienti fically reliable data, useful for 297 assessing the efficacy of the tested material in repelling mosquitoes. In addition, the Board 298 recommended two minor changes to the protocol and associated study documents. First, the 299 protocol should be amended to remove er roneous reference to spray repellents (e.g. the first 300 sentence on page 79, under “Rationale”; Carroll 2010, 79). Second, the Board agreed with the 301 Agency

that reference to sample size standards is now irrelevant in light of recentl y released 302 repellency

tes ting guidelines. Rather than refer to a historical standard of 6 study participants, the 303 proposed sample size should be large enough to be likely to yi eld a definitive answer to the 304 research question and its size justified statistically in the protocol. 305 306 Ethics 307 Charge to the Board 308 If the proposed field repellency study protocol No Mas

- 003 is revised as suggested in 309 EP

A’ s review and if the research is performed as described, is the research likely to meet the a

p310 plicable requirements of 40 CFR part 26, subp arts K and L ? 311 312 Board Response to the Charge 313 HSRB Recommendation 314 The Board concluded that the protocol submitted for review , if modified in accordance 315 with EP

A (Fuentes and Sherman 2010) and HSRB recommendations, is likely to meet the a

p316 plicable requirement s of 40 CFR 26, subparts K and L

. 317Final Draft Document Dated December 8, 2010

Page 10 of 31 HSRB Detailed Recommendation and Rationale 318 The submitted documents assert that the study will be conducted in accordance with the 319 ethical and regulatory standards of 40 CFR 26, Subparts K and L, as well as the requirement s the 320 US EP

A’ s Good Laboratory

Practice ( GLP) Standards described at 40 CFR 160, and the Califo r321 nia State EP

A Department of Pesticide Regulation study monitoring (California Code of Regul a322 tions Ti tle 3, Section 6710) (Carroll 2010). Requirements of FIFRA §12(a)(2)(P) also apply

. The 323 protocol was reviewed and approved b y an independent human subjects review committee, 324 Independent Institutional Review Board (IIRB), Inc. of Plantation, FL prior to submission. IIRB, 325 In c. is fully

accredited by the Association for the Accreditation of Human Research Protection 326 Programs (AAHRPP). IIRB is also listed as an active Institutional Review Board (IRB) on the 327 Of

fice of Human Research Protection ( OHRP) website (Reg. # IORG0002954). Minutes of 328 IIRB, Inc. meetings (Carroll 2010) and a cop y of IIRB, Inc. policies and procedures were pro329 vided to the Agency . These documents indicate that IIRB, Inc. reviewed this protocol pursuant to 330 the standards of the Common Rule (45 CFR Part 46, Subpart A). 331 332 1. Except as noted below , the Bo ard concurred with the conclusions and factual observations of 333 the ethical strengths and weaknesses of the study , as detailed in the EP

A’ s Ethics Review 334 (Fuentes and Sherman 2010). The proposed study is likely to meet the applicable ethical re335 quirements fo r research involving human subjects, in accordance with the following criteria: 336 337
a. Acceptable risk

- benefit ratio. The risks as noted in the study protocol are fivefold: 1) a l338 lergic reaction to test materials themselves; 2) exposure to biting arthropods; 3) possible 339 exposure to arthropod

- borne diseases; 4) phy sical stress from the test conditions; and 5) 340 psychological stress and/or breach of confidentiality for pregnancy

test results. These 341 risks are minimized appropriately and are justified by

the potent ial societal benefits ass o342 ciated with data on the efficacy of the active ingredients, PMD and lemongrass oil, as 343 mosquito repellents. 344 345

• Based on toxicological data currentl y available for PMD and lemongrass oil, 346 coupled with appropriate exclusion criteria, study participants are unlikely

to be at 347 risk of adverse side ef fects with exposure. 348 349

• The study is designed to minimize the likelihood of mosquito bites, through the use 350 of: LIBes rather than actual confirmed bites as a study endpoint; bite removal and 351 joi nt observation; clear stopping rules; and limited periods of exposure to mosqu i352 toes. Study participants will be trained in proper insect observation and handling 353 techniques. 354 355

• Mosquito bites, should they occur, are usually

mild and easil y treated with over

- the

356 counter steroidal creams. The study will also exclude participants who have a hist o357 ry

of severe skin reactions to such bites. 358 359

• Possible exposure to vectors of arthropod

- borne diseases is minimized through the 360 use of certified disease

- free laboratory

- re ared insect populations, selection of field 361 sites in low virus areas, and limited skin exposure. 362 363

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Page 11 of 31

• The potential risks to participants from environmental stress are minimized by the 364 provision of a climate controlled rest area, food, water and medical suppli es, and b y 365 careful monitoring for signs of deh ydration, heat stress and h ypothermia. Appropri366 ate stopping rules and medical management procedures are in place. 367 368

• Minor and pregnant or lactating women are excluded from participation, with pre g369 nancy either co nfirmed by

over- the

- counter pregnancy testing on the day

of study or 370 by

opt

- out. Onl y volunteers scored as non

- pregnant will be allowed to participate. 371 In formation regarding pregnancy test results will be kept confidential. 372 373 b. V

oluntary and informed cons ent of all participants 374

• There is the possibility that the participants in this study might represent particularly 375 vulnerable populations, susceptible to coercion and undue influence. The study prot o376 col, however, includes several mechanisms designed to min imize coercive recruitment 377 and enrollment. 378 379

• The informed consent materials, if changed as recommended by the HSRB below , will 380 adequatel y inform the subjects of the risks, discomforts and benefits from participation, 381 and of their right to withdraw

. 382 383

• Monetary compensation is not so high as to unduly influence participants. 384 385 c. Equitable selection of study participants 386 387

• The majority of research participants will be recruited from the Universit y of California 388 at Davis student population. Study participants are likely to represent the appropriate 389 ethnic and racial diversity of individuals in and around the University , but the use of 390 this convenience sample may limit the broad applicability of the study results to the 391 general population. The investigators have not ed this fact in the protocol (Carroll 2010). 392 393 2. The Board recommended that the study protocol be modified to address the concerns noted in 394 the EP

A’ s Ethics Review (Fuentes and Sherman 2010). In addition, the Board also raised the 395 following concerns: 396 397

• The Board concurred with the Agency ’s recommendation that the protocol be revised to e x398 clude as participants employees of the study sponsor. The Board added the recommend a399 tion that this exclusion also be extended to dependents of the study sponsor or sponsor e m400 ployees. 401 402

• The consent form and protocol should be modified as follows: 403 404 1) Carroll

- Lo ye should add “child/minor” to the list of exclusion criteria. 405 406 2) The term “treatment” is used ambiguousl y throughout the protocol and informed 407 consent form to describe b oth the application of the test materials and treatment for 408Final Draft Document Dated December 8, 2010

Page 12 of 31

research

- related injuries. For example, on page 23 the protocol states that “applic a409 tion of a test material is considered a treatment” (Carroll 2010, 23). Elsewhere, 410 however, the protocol states that “candidates are again encouraged to ask any que s411 tions they have about the study

, which may

include understanding ... treatment and 412 compensation for injury more fully” (Carroll 2010, 17, 238). This ambiguity should 413 be resolved with the use of a dif ferent term to describe the application of test mat e414 rials. 415 416 3) On page 16, the protocol states that “...dosimetry subjects may

be consented before 417 repellency subjects. Untreated control subjects for the repellency phase (field study) 418 are consented before the treat ed subjects for that phase...” (Carroll 2010, 16). The 419 verb “to consent” is an intransitive verb; from a grammatical point of view , som e420 one cannot “be consented.” From an ethical perspective, this infelicitous use of the 421 verb also emplo ys the passive voice, which is not best practice when the issue is to 422 affirm that researchers will be accountable for obtaining informed consent. It is 423 recommended that the protocol be modified to use alternate phrasing such as “R e424 searchers may obtain informed consent from dos imetry subjects before repellency 425 subjects ...” 426 427 4) Carroll

- Lo ye should spell out the acron ym“PMD” when it is first used in the prot o428 col and consent form. 429 430 5) On page 2 of the consent form, the phrase “Y ou have been of

fered an opportunity

to 431 participate in this research study because ...” (Carroll 2010, 199, 209, 219) be mo d432 ified by Carroll

- Lo ye to minimize the impression that participation in this intentio n433 al exposure study is somehow a beneficial or favorable occasion. A neutral altern a434 tive might be: “W e ar e asking you to participate in this research study because...” 435 436 6) A description of the sy mptoms of heat stress and equine encephalitis should also be 437 included in the consent form. Currently , onl y the symptoms of W est Nile V irus are 438 listed. 439 440 Assessment of P ro posed AHETF Scenario and Pr otocol AHE

- 400: Backpack and Handgun 441 Application of Liquid Sprays in Utility Rights

- of

- Wa y. 442 443 Overview of the Study 444 445 This proposal presents an agricultural handler exposure scenario involving backpack and 446 handgun application of liquid pesticides along utility rights

- of

- way

. The protocol calls for study 447 participants to appl y (and potentially load) four surrogate pesticides (fosamine, gl yphosate, 448 imazapy

r and 2,4

- D). A total of 21 participants (described in the protocol as “Monito ring Units” 449 [MUs]) will be observed for each scenario; three volunteers each from seven geographically 450 distinct growing regions will be enrolled using a purposive sampling method (with some 451 elements of random selection). 452 453

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Final Draft Document Dated December 8, 2010

Page 13 of 31 Dermal exposure will be measured by a whole body

dosimeter (WBD) worn beneath the 454 subject’ s outer clothing. Hand wash and face/neck wipe samples will also be collected prior to, 455 during, and after completion of pesticide loading and mixing procedures. Airborne concentr a456 tions of the surrogate will be monitored in the participant’ s breathing zone using an OSHA V e r457
s atile Sampler (OVS) tube sample collector connected to a personal sampling pump. Additional 458 measures will also record environmental conditions at the time of monitoring, and observe rs will 459 make field notes, photographs and videos of participant activity throughout the monitoring event. 460 461 The results of sample analy sis under the backpack and handgun application scenario will 462 be posted to the AHED® database, where they will be availabl e to the EP A and other regulatory 463 agencies for statistical analy sis. The proposed documentation will report a confidence

- interval

464 based approach to determine the relative accuracy for the arithmetic mean and 95 th percentile of 465 unit exposures. The Agency pr oposes to use these data to estimate dail y dermal and inhalation 466 exposures of agricultural handlers who are applying pesticides using backpack and/or handgun 467 applicators under a variety of scenarios. 468 469 Science 470 471 Charge to the Board 472 473 If the proposed AHETF Ri ght

- of

- Wa y application scenario and field study proposal 474 AHE400 is revised as suggested in EP A’ s review and if the research is performed as described, is 475 the research likel y to generate scientificall y reliable data, useful for assessing the exposure of 476
wor

kers who appl y pesticides in utility rights

- of

- way using backpack or handgun spray ers? 477 478 Board Response to the Charge 479 480 HSRB Recommendation 481 482 The Board concurred with the Agency ’s assessment that the proposed AHETF Right

- of

483 Way application scenario and fie ld study proposal AHE400, if revised as suggested in EP A’ s 484 review (Evans and Sherman 2010a) and performed as described, is likely to generate 485 scientifically

reliable data useful for assessing the exposure of workers who apply pesticides in 486 utility

rights

- o f

- way using backpack or handgun spray ers. 487 488 HSRB Detailed Recommendations and Rationale 489 490 Given the lack of existing reliable and sound data in this area, the Board concurred with 491 the Agency ’s assessment (Evans and Sherman 2010a) that this protocol will li kely generate data 492 that may

be useful for assessing the exposure of handlers who appl y pesticides using backpack or 493 handgun sprayers

. 494 495 The study

, if conducted as described, will provide newer exposure information on dermal 496 and inhalation exposures of pes ticide handlers using backpack sprayers and handgun sprayers 497 treating utility

rights

- of

- way in appropriate and distinct geographic locations; some study parti c498 ipants will be exposed during loading backpacks or tanks as well. The Board agreed with the 499Final Draft Document Dated December 8, 2010

Page 14 of 31 Agenc y’ s assessment that the protocol adequatel y addresses a number of scientific questions, i n500 cluding having clear scientific objectives, a reasonable experimental design for achieving these 501 objectives: appropriate quantification of test materials, adequate procedures for collecting, co m502 piling and summarizing test results, appropriate justification for selection of test substances, 503 sample size, and study site selection, and acceptable QA/QC procedures. 504 505 However, the Board noted a few weaknesses in the proposed study design. In particular, 506 the variability

in individual dermal and inhalation exposure levels may be extremely

high b e507 cause of the diversit y of terrains and locations selected for the study and the opportunity for large 508 (but potentially

categorical) pe rsonal differences in application practices. The proposal to impose 509 a minimum exposure duration of at least 4 hours will also create opportunities for the applic a510 tor’s exposures to be influenced b y variables that by their nature are likel y to be unrelated to the 511 amount of active ingredient handled (AaiH). Should this diversity yield high variability

in the 512 data sets, then the proportionality of exposure with AaiH may not be apparent. If the 4

- hour mi n513 imum is not removed, the Task Force may want to ensure th at field notes are adequate to report 514 time

- on - task as a fraction of the total monitored time for use in later data analy sis and usage 515 within AHED. he rationale for having and using this “fraction” is discussed more fully in the 516 Board’s discussion of protoc ol AHE120 below. Even if the proportionalit y hypothesis is not sup517 ported by

the resultant data sets, these data are likely to still be useful and relevant to assessing 518 the levels of exposure to workers applying pesticides to utility rights

- of

- way

. 519 520 Ethics 521 Charge to the Board 522 If the proposed AHETF Right

- of

- Wa y application scenario and field study proposal 523 AHE400 is revised as suggested in EP A’ s review and if the research is performed as described, is 524 the research likel y to meet the applicable requirements of 40 CFR part 26, subparts K and L ? 525 526 Board Response to the Charge 527 HSRB Recommendation 528 The Board concluded that the protocol submitted for review , if modified in accordance 529 with EP

A (Evans and Sherman 2010a) and HSRB recommendations, is likely to meet th e a

p530 plicable requirements of 40 CFR 26, subparts K and L

. 531
HSRB Detailed Recommendation and Rationale 532 The submitted documents assert that the revised study will be conducted in accordance 533 with the ethical and regulatory standards of 40 CFR 26, Subparts K and L , as well as the r e534 quirements the US EP A’ s GLP Standards described at 40 CFR 160 (AHETF 2010a; Collier 535 2010a). FIFRA

§12(a)(2)(P) also appl ys

. The protocol was reviewed and approved b y an ind e536 pendent human subjects review committee, IIRB, Inc. of Plantation, FL prior to submission. M i537 nutes of IIRB, Inc. meetings and a cop y of IIRB, Inc. policies and procedures were provided. 538 This IRB is fully

accredited by

AAHRPP

and listed by

OHRP (see details above). 539 540

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Final Draft Document Dated December 8, 2010

Page 15 of 31 1. Except as noted below , the Board concurred w ith the conclusions and factual observations of 541 the ethical strengths and weaknesses of the study , as detailed in the EP

A’ s Ethics Review 542 (Evans and Sherman 2010a). The proposed study i s likely to meet the applicable ethical r e543 quirements for research invol ving human subjects, in accordance with the following criteria: 544 545
a. Acceptable risk

- benefit ratio. Risks as noted in the study protocol are four

- fold: 1) heat

546 related illness; 2) injury associated with scripted field activities; 3) allergic reaction to 547
s urfactants using for hand washing; and 4) ps ychological stress and/or breach of confi548 dentiality

for pregnancy

test results. These risks are minimized appropriately and are ju s549 tified by

the potential societal benefits, particularly data for new exposure ass essments 550 for occupational risks associated with spraying pesticides to rights

- of

- way using bac k551 pack and handgun spray ers. 552 553

• Only experienced pesticide handlers, with specific experience with the t ype of ap554 plication equipment to be used, and who consider the mselves to be in good health, 555 will be enrolled. 556 557

• Risk of heat

- related illness is minimized appropriately . Heat index will be mon i558 tored with an associated stopping rule. A medical professional will be on site to o b559 serve the workers and provide urgent care. Nearby medical facilities have been 560 identified in case of emergency , and transportation to medical treatment will be 561 provided, if needed. 562 563

• Subjects will be reminded about safe chemical handling practices and procedures, 564 wearing appropriate personal prote ctive equipment (PPE), and will be monitored for 565 any

accidental or unintended product exposure. 566 567

• Minors and pregnant or lactating women are excluded from participation, with 568 pregnancy either confirmed by

over- the

- counter pregnancy testing on the day

of 569 study or b y opt

- out. The potential stigma resulting from study exclusion due to 570 pregnancy is appropriately

minimized. 571 572 The Board disagreed with the AHETF conclusion, however, that “the risk of toxicity from 573 pesticide handling [is not] strictly due to study participation [and therefore], the risk of 574 surrogate toxicity will not be listed in consent forms or this protocol” (Collier 2010a, 575 309). This study is subject to 40 CFR 26 subparts K and L precisel y because it is cons i576 dered to be a study in which the subj ects are “intentionally exposed,” for research pur577 poses, to pesticides. Given its scripted nature, the AHETF protocol influences the beh a578 vior of workers and their employ ers in a number of way s. That a particular agricultural 579 worker will be applying a parti cular pesticide on a particular day is due, to a large extent, 580 to the fact that the study is being conducted. Accordingly , the risk from exposure to the 581 pesticides being applied should clearl y be categorized as a risk of study participation. 582 583 The Board doe s agree, however, that the risk from exposure to those pesticides is a re a584 sonable one, and that it has been appropriatel y minimized. The products being used in 585Final Draft Document Dated December 8, 2010

Page 16 of 31 this study are ones already

registered by

EP A for vegetation control in rights

- of

- way , and 586 will be applied in accordance with label requirements. 587 588 b. V

oluntary and informed consent of all participants 589

• There is the possibility that the participants in this study might represent particularly 590 vulnerable populations, susceptible to coercion and undue influence. The study prot o591 col, however, includes several mechanisms designed to minimize coercive recruitment 592 and enrollment. 593 594

• The informed consent materials, if changed as recommended by the HSRB below , will 595 adequatel y inform the subjects of the risks, di scomforts and benefits from participation, 596 and of their right to withdraw

. 597 598

• Monetary compensation is not so high as to unduly influence participants. 599 600

• Spanish translations of the informed consent documents, informational packets, and r e601 cruitment flyers wer e provided. Researchers will be working with local Spanish

602 speaking community members to ensure that the appropriate regional dialect of Spanish 603 is used (AHETF 2010b). 604 605 c. Equitable selection of study participants 606 607

• The study is designed to recruit an appro priatel y diverse population of participants who 608 represent skilled workers in the study locations. 609 610

• The study will first involve identifying and contacting the employers involved in right

611 of

- way application of pesticides. Only employees of these employers are eligible to be 612 recruited. The recruitment process has been carefully designed to assure that employees 613 will not be coerced into participating: recruitment will take place using brochures and 614 meetings with emplo ye es at which the employer and supervisors will not be present. 615 616 2. The Board recommended that the study protocol be modified to address the concerns noted in 617 the EP

A’ s Ethics Review (Evans and Sherman 2010a). In addition, the Board also raised the 618 following concerns: 619 620

• As noted above, the Board c oncluded that the risk of toxicity from pesticide handling is i n621 deed a risk of participating in the study , and accordingl y it should be described as such, and 622 discussed appropriately , in the consent form. 623 624

• The consent form should explain that the pregnancy test will be provided b y the researc h625 ers, and explain when it will take place. 626 627

• There appears to be a discrepancy between the exclusion criteria stated in the EP A review 628 (Evans and Sherman 2010a, 36), which refer to training in handling pesticides, and th e 629 AHETF

- provided consent form (AHETF 2010a, 267), which notes that the subject might 630

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Final Draft Document Dated December 8, 2010

Page 17 of 31 need onl y to confirm that “you are not required to take this training.” This discrepancy 631 should be clarified. 632 633

• Study participants will undergo hand washes prior to eating an ything, which will reduce 634 their risk of accidental ingestion of the surrogate compounds. As man y of the adults in the 635 US still smoke, however, hand washes should also occur before an y smoking break to fur636 ther reduce participant’ s risk of accidental pesti cide ingestion. 637 638 Assessment of Completed AEA TF II Resear ch Study AEA

- 03: A St udy for Measur ement of 639 Potential Dermal and Inhalation Exposur e during Application of a Liquid Antimicr obial 640 Pesticide Pr oduct Using Bucket and Mop Equipment for Cleaning Indoor

S urfaces (MRID 641 48210201, MRID 48231201, MRID 48231901). 642 643 Overview of the Study 644 645 The o bjective of this study was to measure individual exposures to a surrogate antimicro646 bicidal pesticide (didecyl dimethyl ammonium chloride; DDAC) while mopping floors and emp647 tying mop buckets. Eighteen volunteers participated in the study , mopping floors in one of three 648 building ty

pes (an of fice building, a Rite Aid pharmacy building, or a retired teacher ’s memorial 649 building in Fresno, CA) for one of six pre

- determined moppi ng times (30

- 40, 40

- 50, 50

- 60, 60

- 650 70, 70

- 80 and 80

- 90 minutes total mopping time, respectivel y). 651 652 Dermal and inhalation exposure monitoring was conducted while study participants 653 mopped floors and emptied the mop buckets; all participants wore long

- sleev ed shirts, long 654 pants, shoes, socks, and no gloves. Dermal exposure was measured b y inner and outer body d o655 simeters. Airborne concentrations of the surrogate compound were monitored in the participant’ s 656 breathing zone using an OSHA V ersatile Sampler (OVS) tube sample collector connected to a 657 personal sampling pump. Environmental conditions were also recorded at the time of monitoring, 658 and observers made notes, photographs and videos of participant activity throughout the mo p659 ping period. 660 661 These exposure dat a will be used to populate a database representing inhalation and de r662 mal exposure during a number of antimicrobial handler scenarios. A scenario is defined as a pe s663 ticide handling task based on activity (e.g., application) and equipment t yp e (e.g., mop & b ucket, 664 read y - to

- use wipes, pressure treatment of wood facilities, painting). These data will be used by 665 the Agency

to estimate dermal and inhalation exposures of antimicrobial handlers who are appl y666 ing pesticides using a mop and bucket under a variety of s cenarios. 667 668 Science 669 670 Charges to the Board 671 672 1) Wa s the research reported in the Antimicrobial Exposure Assessment Ta sk Force II (AEA TF

– 673 II) completed study report AEA

- 03 and associated supplemental reports faithful to the design 674 and objectives of the protoco l and governing documents of AEA TF

- II? 675 676Final Draft Document Dated December 8, 2010

Page 18 of 31 2) Has the Agency

adequately

characterized, from a scientific perspective, the limitations on 677 these data that should be considered when using the data in estimating exposure of those who 678 apply

antimicrobial floor

- cl eaning products with mop and bucket? 679 680 Board Response to the Charge 681 682 HSRB Recommendation 683 684 The Board concurred with the Agency ’s assessment (Leighton 2010) that the research 685 reported in the completed AEA

- 03 study report and associated supplemental documents (Selim 686 and T

aylor 2010a, 2010b, 2010c) was conducted in a manner that was reasonably faithful to the 687 design and objectives of the protocol and governing documents of AEA TF

- II. The Board also 688 concluded that the Agency has adequately

, if not completely

, c onsidered the limitations on these 689 data that should be considered when using the data in estimating exposure of those who appl y 690 antimicrobial floor

- cleaning products with mop and bucket. 691 692 HSRB Detailed Recommendations and Rationale 693 694 The study

was conducte d in a manner that was reasonably faithful to the design of the 695 protocol and governing documents. The study report (Selim and T aylor 2010a) contains sections 696 that adequatel y describe the test substance, recruitment procedures, field procedures, sample 697 coll ection and handling, sample anal ys is, and data anal ys is. Previous Board recommendations 698 (EP

A HSRB 2008) for the use of a double lay er of socks and provision of more detail about staff 699 activities during the observation period were adopted. Appropriate ratio nale for changes in key 700 elements of the study design, including justification for the purposive sampling of monitoring 701 events (MEs) and the sample size of 18, was also provided. Finally , assuming that onl y one 702 participant was present in the cluster when an ME was conducted, it also appears that no 703 participant observed another participant’ s activities during the study , as previously 704 recommended. However, some of the issues raised by the Board in its initial review of the mop 705 and bucket scenario (EP A HSRB 200 8) were not addressed, including: the bases for the 90

- 706 minute maximum mopping period choice, the possibility (or not) of “carry

- over ef fects” between 707 MEs, and the interaction between aerosolized particles, heating, ventilation and air conditioning 708 (HV

AC) s ys tems, and inhalation exposure estimates. Although the importance of measuring the 709 impact of HV

AC s ys tems on inhalation exposures was mentioned in the protocol (Selim and 710 Tayl or 2010a, 28), it was not given appropriate attention nor were HVAC operations c onsistently 711 documented during the conduct of the study . While this lack of information places potentiall y 712 important limitations on how the inhalation data should be interpreted , in the professional 713 opinion of at least one Board member the impact of differences among the test sites are likel y to 714 be within a factor of about two and thus not substantively change the overall mean exposure 715 levels. The study

was also conducted in a manner that was reasonably faithful to the objectives 716 of the protocol and governin g documents. As stated in the final report, the study was conducted 717 primarily

to “determine potential dermal and inhalation exposures to professional janitorial 718 workers when mopping indoor surfaces with a liquid antimicrobial pesticide product containing 719 d idecyl dimethyl ammonium chloride (DDAC)” (Selim and Tayl or 2010a, 28). Dermal exposures 720 were reported, with estimates based on total collected residue from all matrices (face and hand 721 wipes, socks, and all parts of the inner dosimeter). Dermal exposures w ere expressed as 722

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Final Draft Document Dated December 8, 2010

Page 19 of 31 micrograms of active ingredient (AI) handled per subject and as milligrams of AIper 723 subject/pound of AIapplied. Inhalation exposure was also presented as units of concentration. 724 However , sufficient data is available ( i.e. , the duration o f each e xposure) to express those results 725 in the same units as dermal exposures if an average respiratory minute volume for the appicators 726 is also applied to the calculation. 727 728 The overall study objective was listed dif

ferentl y i n the Agency ’s scientific r eview than in 729 the protocol, stating it as: “the study objective is to monitor inhalation and dermal exposures to 730 be used as inputs in exposure algorithms to predict future exposures to persons mopping floors.” 731 (Leighton 2010, 5). The Agency added two sub

- objectives not found in the protocol: “to be 95% 732 confident that key statistics of normalized dermal exposure are accurate within 3

- fold ” and “to 733 evaluate the presumption of proportionality between exposure and amount of active ingredient 734 handled,” respect ivel y. T he Agency provided a thorough assessment of the ir first sub

- objective 735 supporting the sample size and analy ses used to achieve the 3

- fold accuracy goal. However, 736 although the presumption of proportionality was demonstrated for dermal exposure and th e 737 amount of AIhandled, the rationale supporting the presumption of proportionality for inhalation 738 exposure needs to be recalculated but based on current data may not be as clear and consistent as 739 for the dermal exposure. 740 741 The Agency ’s scientific review (Leighton 2010) discussed the limitations of the dermal 742 and inhalation exposure data. The Agency also presented alternative models for estimating 743 dermal and inhalation exposures, evaluated the impacts of non

- detects and of assigning low 744 limits of quantific ation (LOQs) at 3 different values (0, 1⁄2 and full LOQ). The Agency concluded 745 that dermal exposures and pounds of active ingredient are related in a proportional manner , while 746 accounting for sampling ef ficiency and normalizing the data in terms of milligram s/pounds of 747 active ingredient applied. The Agency also discussed the dermal exposure estimates in 748 relationship to its sub

- objectives of the study (accuracy within 3

- fold and proportionality). Their 749 assessment acknowledged that some estimates included a high level of uncertainty and some 750 bias. The Board concluded that the Agency adequately

, if not completely

, considered limitations 751 in its interpretation and sub se quent estimates of dermal exposure data. One Board member 752 observed, however, that the Agency ’s re liance on hand wash data may have over

- corrected face 753 and neck residue estimates. Another Board member questioned whether the model actuall y 754 supports the conclusion of proportionality for some of the dermal configurations. 755 756 Wi th respect to limitations of the inhalation exposure data due to study deviations, some 757 (but not all) of the limitations that need to be considered when estimating inhalation exposure 758 were discussed. In its initial 2008 review (EP A HSRB 2008), the Board noted several factors that 759
cou ld influence these estimates, including: ventilation, room temperature, total area mopped, 760 duration of mopping, and volume of the enclosed space and respiration rate of the study 761 participants. Although the final study report provides some of these data for the facilities in 762 which mopping activities were conducted (Selim and T aylor 2010a, 105

- 7), n either ventilation 763 data nor a discussion of these factors were provided, thus limiting the Board’ s and Agency ’s 764 ability

to interpret full y the reported environment al data. Furthermore, the rationale for the 765 Agency ’s conclusion that air changes per hour was not a significant factor influencing inhalation 766 exposure estimates, based on the low vapor pressure of DDAC and the LOQs observed, does not 767 recognize full y how HV AC parameters could have affected reported air concentrations from 768Final Draft Document Dated December 8, 2010

Page 20 of 31 mopping activities. The Agency also failed to consider whether the limited areas available for 769 mopping in Clusters 1 and 3 could have compromised the study design or affected inhalation 770 exp osure estimates. Similarly , although surface areas of the floors mopped were noted, the 771 ceiling heights were not reported. The Agency ’s review also fails to consider the impact that 772 ceiling height and room volume may have had on the reported air concentrat ion data. The 773 respiration rates of study participants were not discussed by the T ask Force researchers or the 774 Agency ; ignoring this factor could introduce important uncertainties into exposure estimates. 775 Finally

, the Board’ s previous recommendation to c onsider particle size (e.g., whether DDAC is 776 aerosolized) and its potential impact on inhalation exposures w ere not addressed b y the Agency

. 777 Although not discussed in detail by the Board at the October 2010 meeting, several of these 778 factors are discussed i n Appendix 1 below (written as a separate report by HSRB member Dr. 779 William Popendorf). 780 781 Ethics 782 Charge to the Board 783 Does available information support a determination that the study was conducted in sub784 stantial compliance with subparts K and L of 40 CFR P art 26? 785 786 Board Response to the Charge 787 HSRB Recommendation 788 789 The Board concurred with the Agency ’s assessment (Carley 2010) that the study

was 790 conducted in substantial compliance with subparts K and L 40 CFR 26. 791 792 HSRB Detailed Recommendation and Rationa le 793 794 The documents provided by Golden Pacific Laboratories, LL C, under Project No. AEA

795 03, state that the study was conducted in compliance with the requirements of 40 CFR 26 796 subparts K, L

and M; FIFRA

§ 12(a)(2)(P); and the California Code of Regulations Title 3, 797 Section 6710 (Selim and T aylor, 2010a, 2010b, 2010c). The protocol was reviewed and approved 798 by an independent human subjects review committee, IIRB, Inc. of Plantation, FL prior to 799 submission. Minutes of IIRB, Inc. meetings and a copy of IIRB, Inc . policies and procedures 800 were provided. This IRB is fully accredited b y AAHRPPand listed by OHRP (see details above). 801 802 1. The Board concurred with the conclusions and factual observations relating to the study , as 803 detailed in the EP A’ s Ethics Review (Carley 2010) and summarized briefl y below

. 804 805
a. Prior HSRB and Agency Review. Because this study was initiated after 7 April 2006, 806 prior submission of the protocol and supporting materials to EP A was required by

40 807 CFR §26.1 125. The requirements of 40 CFR § 26.1 125 for prior submission of the 808 protocol to EP A and of §26.1601 for HSRB review of the protocol were satisfied. The 809 scenario design and study were approved b y IIRB, Inc. and submitted to the EP A in 810 February

2008. The HSRB discussed the protocol at its April 2008 meeting, concurring 811 with the Agency ’s assessment that the proposed mop and wipe scenario, if revised as 812

# DRAFT

Final Draft Document Dated December 8, 2010

Page 21 of 31 suggested b y the Agency

and the HSRB, would meet the applicable requirements of 40 813 CFR part 26, subparts K and L

. 814 815 b. Responsiveness to HSRB and Agency Recommendations. 816 817 The Agency ’s initial ethics review noted two deficiencies to be corrected before the study 818 was initiated. The first focused on measures to improve the informed consent process for 819 Spanish

- speaking candidates. The Agency called for the candidate interviews for Spanish 820 speakers to be conducted by a member of the research team fluent in Spanish, rather than 821 an independent translator. The second deficiency focused on references in the informed 822 consent forms to “normal business hour s”. The Agency asked that the researchers revise 823 the consent form to show hours for calling in local (Pacific) time. 824 825 In the revisions submitted to IIRB, Inc. in February 2009, the researchers addressed these 826 ethical concerns. Because the study was cond

ucted in California, the approval of the 827 California Department of Pesticide Regulation (CDPR) was also required. CDPR granted 828 final approval of the amended protocol and supporting documents in April 2009. 829 830 b. Responsiveness to HSRB and Agency Reviews. Th e Agency ’s and HSRB’ s comments 831 were satisfactoril y addressed in the revisions approved by the IIRB in March 2009 (Selim 832 and T

aylor 2010a). 833 834 At its April 2008 meeting, the HSRB made several specific recommendations for 835 refinements of the study

. As noted in Amendment 4 of the Agency ’s ethics review 836 (Carley

2010), the investigators addressed full y most of these recommendations, 837 addressed partiall y some of these recommendations, and did not address two of these 838 recommendations. The Board agreed with the Agen cy conclusion, however, that the 839 investigators’failure to address all of the recommendations did not violate applicable 840 ethical standards for the protection of human participants of research. 841 842
c. Substantial Compliance with Reporting Requirements (40 CFR §26 subpart M). 843 844 The study

sponsor initially

did not provide adequate documentation to demonstrate that 845 they

had satisfied the requirements of §26.1303. The initial report (Selim and Ta yl or, 846 2010a) contained several reporting deficiencies, including: in adequate documentation of 847 interaction between the investigators and the overseeing IRB, incomplete study 848 chronology , and a lack of tracked consent forms showing how they were revised to 849 address Agency and HSRB concerns. These deficiencies were corrected b y the 850 submission of supplemental documents (Selim and T aylor, 2010b, 2010c). 851 852 IRB minutes documenting discussion and review of these revised documents were not 853 provided for review

. All IIRB, Inc. reviews subsequent to the HSRB’ s April 2008 854 meeting were c onducted using an expedited procedure and did not require a full meeting 855 of the IRB. Neither the IRB roster nor the operational procedures were submitted as part 856 of the study documents. 857 858Final Draft Document Dated December 8, 2010

Page 22 of 31 The HSRB agreed with the Agency that these deficiencies in the con duct and the 859 documentation of the research did not compromise the ethical conduct of the study , and 860 concluded that the requirements of 40 CFR §26.1303 were satisfactoril y addressed. The 861 HSRB did recommend, however, that the Agency require the submission o f reports for all 862 research that undergoes expedited IRB review in the future. 863 864 2. The Board concluded that this study , as conducted, met all applicable ethical requirements for 865 research involving human participants, in accordance with the following crite ria that had 866 been stated in the Board’ s prior review of this protocol (EP A HSRB 2008). 867 868
a. Acceptable risk

- benefit ratio. The risks to study participants were minimized 869 appropriatel y and were justified by the potential societal benefits, particularly data on the 870 dermal and inhalation exposure of professional janitorial workers to antimicrobial 871 pesticides as they mopped indoor floors and disposed of spent mop water. These data 872 could be used to develop mechanisms to protect future users of these antimicrobial 873 pesticides. 874 875

• Minors and pregnant or lactating women were excluded from participation, with 876 pregnancy confirmed by

over- the

- counter pregnancy testing on the day

of study or b y 877 opt

- out. The potential of stigma resulting from study exclusion was also appropriatel y 878 minimized. 879 880

• Clear stopping rules and medical management procedures were in place, and no adverse 881 events or other incidents of concern related to product exposure were reported. 882 883

• The study was designed to minimize the risks of exposure to the test c ompounds. 884 885 b. Vo luntary

and informed consent of all participants 886 887

• The study protocol included several mechanisms designed to minimize coercive 888 recruitment and enrollment. 889 890

• Monetary compensation was not so high as to unduly influence participation. 891 892 3. Thr ee minor protocol deviations were reported. These included: 1) most study participants 893 declining to take rest breaks or taking less than the 10 minutes provided for in the protocol; 894 2) full facial photographs taken of participants at one monitoring site; and 3) enrollment of 895 participants who self

- reported that their health was only “fair,” despite the requirement that 896 all participants be in “good health” (Selim and T aylor, 2010b, 31). The Board concluded, 897 however, that these minor deviations did not af fect the integrit y of the research or the safety 898 of participants. The Board did recommend, however, that sponsors clarify the criteria used to 899 establish participants’health status prior to study enrollment. 900 901

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Final Draft Document Dated December 8, 2010

Page 23 of 31 Assessment of Revised AHETF Scenario and Pr otocol AH E

- 120: Water

- Soluble Packaging 902 Mixing and Loading. 903 904 Overview of the Study 905 906 This revised proposal presents an agricultural handler exposure scenario involving 907 mixing/loading of pesticides enclosed in water

- soluble packets (WSP). The original protocol, 908 whic h was favorabl y reviewed b y the Board at its June 2009 meeting (EP A HSRB 2009), called 909 for study

participants to mix and load one of two WSP

- enclosed surrogate pesticides (acephate 910 and carbaryl) into a variety of tanks containing water in a variety of agri cultural spraying 911 operations. Carbaryl in water

- soluble packaging is no longer being produced by pesticide 912 manufacturers; however, the AHETF proposed substituting three additional surrogate compounds 913 for carbaryl: dithiopy r, imidacloprid, and thiophanate

- m eth yl . Because of use patterns of these 914 surrogate compounds, the AHETF also identified additional study sites. The previousl y reviewed 915 study

was to be conducted at three cool dry sites in Michigan, New Yo rk, and Wa shington State, 916 one hot humid site in L oui siana, and one hot dry site in California. The revised protocol will also 917 be conducted at five sites, including two cool dry sites in New Yo rk and North Dakota, two hot 918 humid sites in Florida and L ouisiana, and one hot dry site in California. 919 920 A total of 25 participants (described in the protocol as “Monitoring Units” [MUs]) will be 921 observed; five volunteers each from five different growing regions will be enrolled using a 922 purposive sampling method. Dermal exposure will be measured b y a whole body dosimete r 923 (WBD) worn beneath the subject’ s outer clothing. Hand wash and face/neck wipe samples will 924 also be collected prior to, during, and after completion of pesticide loading and mixing 925 procedures. Airborne concentrations of the surrogate will be monitored in the participant’ s 926 breathing zone using an OSHA V ersatile Sampler (OVS) tube sample collector connected to a 927 personal sampling pump. Additional measures will also record environmental conditions at the 928 time of monitoring, and observers will make field notes , photographs and videos of participant 929 activity

throughout the monitoring event. 930 931 The results of sample analy sis under the mixing/loading of water

- soluble packets 932 scenario, and will be posted to the AHED® database, where they will be available to the EP A 933 and other regulatory agencies for statistical analysis. The Agency proposes to use these data to 934 estimate daily

dermal and inhalation exposures of agricultural handlers who are mixing/loading 935 pesticides in water

- soluble packets under a variet y of mixing and loading scenarios. 936 937 Science 938 939 Charge to the Board 940 941 If the revised AHETF scenario and field study proposal AHE120 is revised as suggested 942 in EP

A’ s review and if the research is performed as described, is the research likely to generate 943 scientifically

re liable data, useful for assessing the exposure of handlers who mix and load pest i944 cides in water

- soluble packaging? 945 946Final Draft Document Dated December 8, 2010

Page 24 of 31 Board Response to the Charge 947 948 HSRB Recommendation 949 950 The Board concurred with the Agency ’s assessment (Evans and Sherman 2010b) that this 951 p rotocol will generate data that are scientificall y valid and that may be useful for assessing the 952 exposure of handlers who mix and load soluble or wettable powder pesticides in water

- soluble 953 packaging. The Board cautioned, however, that these data might no t be useful for creating 954 distributions of worker exposure that are scientifically accurate or that are precise. 955 956 HSRB Detailed Recommendations and Rationale 957 958 The protocol is largely the same as when it was first reviewed b y the HSRB in June 2009 959 (EP

A HSRB 2009). The major changes are that one of the surrogate active ingredients (carbaryl) 960 was deleted and three other active ingredients (dithiopy r, imidacloprid, and thiophanate

- methyl) 961 were added. This change necessitated revising the geographical regions in which the study could 962 be conducted and a slight lowering of each of the five strata in the amounts of active ingredient 963 handled. 964 965 Each of these changes seems justified. Assuming that the AHETF can provide adequate 966 evidence of the validity of the ana ly

tical methods for each of the new compounds, the revised 967 study

protocol still allows a good probability of the study

successfull y obtaining its primary and 968 secondary

objectives (i.e., “that selected lognormal

- based estimates of normalized dermal exp o969
sure distribution be accurate to within 3

- fold, at least 95% of the time,” and the ability to disti n970 guish “a proportional from an independent relationship between exposure and AaiH,” respectiv e971 ly (Evans and Sherman 2010b, 28

- 9). 972 973 However, the Board pointed out that many of the same concerns it raised in June 2009 974 remain for the revised protocol. Of particular note is the conflict between the non

- random, pur975 posive study

design and the statistical methods proposed to anal yz e the exposure data. Moreover, 976 the pro tocol does not control for ecological, engineering, and statistical factors that may obscure 977 a linear relationship between AaiH and worker exposure. Previously the Board said that “there is 978 no statistical theory that can be applied to non

- random samples o f this ty pe. Thus, the statistical 979 anal ys es proposed, including mixed model approaches, are not valid” (EP A HSRB 2009, 34). In 980 contrast to the prior version, this protocol indicates that AHETF will not statistically analyze the 981 monitoring data; that begs the question as to what statistical methods are appropriate to use on 982 these data. 983 984 The Board also raised one new concern regarding the potentially adverse impact of the 985 protocol’ s call for an exposure duration of at least 4 hours for all of the MUs. Th is constraint 986 seems unnecessary and may introduce unintended and undesired variability into the results. The 987 Board noted that scripting activities to include more time than would otherwise be required to 988 apply

the amount of active ingredient in the design ated stratum is likely to change the applic a989 tor ’s exposures by introducing variables that by their nature are unrelated to the AaiH. In parti c990 ular, other tasks within those hours are likely to result in the transfer of active ingredient either to 991 or from other surfaces from or onto the subject. For this study , the fraction of the total monitored 992

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Final Draft Document Dated December 8, 2010

Page 25 of 31 time that is time on

- task is likely to be highly

variable, probabl y among strata (particularl y if the 993 artificial constraint on the minimum time monitored affects the low AaiH preferentiall y) and p o994 tentially

even within strata. While omitting this time constraint would avoid these random v a995 riables, the Board recommended that all field notes for this study report the time on

- task as a 996 fraction of the total monitored t ime, and that the total monitored time and the fraction of the total 997 time on

- task be tabulated for this study

. This fraction can be used later by the Agency , sponsors 998 and AHED users to reliably extrapolate from the time

- weighted average concentrations or r ates 999 of exposure measured b y the existing protocols to task

- specific concentrations or rates of dermal 1000 and inhalation exposure per AaiH. 1001 1002 Ethics 1003 Charge to the Board 1004 If the revised AHETF scenario and field study proposal AHE120 is revised as suggested 1005 in E PA

’s review and if the research is performed as described, is the research likely to meet the 1006 applicable requirements of 40 CFR part 26, subparts K and L ? 1007 1008 Board Response to the Charge 1009
HSRB Recommendation 1010 The Board concluded that the protocol submitted for review, if modified in accordance 1011 with EP

A (Evans and Sherman 2010b) and HSRB recommendations, is likely to meet the appl i1012 cable requirements of 40 CFR 26, subparts K and L. 1013 1014 HSRB Detailed Recommendation and Rationale 1015
The submitted documents assert th at the revised study will be conducted in accordance 1016 with the ethical and regulatory standards of 40 CFR 26, Subparts K and L , as well as the r e1017 quirements the US EP A’ s GLP Standards described at 40 CFR 160 (AHETF 2010c; Collier 1018 2010b). FIFRA

§12(a)(2)(P) and the California State EP A Department of Pesticide Regulation’ s 1019 study

monitoring requirements (California Code of Regulations Ti tle 3, Section 6710) also apply

. 1020 The protocol was reviewed and approved b y an independent human subjects review committee, 1021 IIRB , Inc. of Plantation, FL prior to submission. Minutes of IIRB, Inc. meetings and a copy of 1022 IIRB, Inc. policies and procedures were provided. This IRB is fully accredited by

AAHRPP

and 1023 listed by

OHRP (see details above). 1024 1025 1. Except as noted below , the Board concurred with the conclusions and factual observations of 1026 the ethical strengths and weaknesses of the revised study , as detailed in the EP

A’ s Ethics R e1027 view (Evans and Sherman 2010b). The proposed study is likely to meet the applicable ethical 1028 requireme nts for research involving human participants, in accordance with the following cri1029 teria: 1030 1031
a. Acceptable risk

- benefit ratio. Risks as noted in the study protocol are four

- fold: 1) heat

1032 related illness; 2) injury associated with scripted field activities; 3 ) allergic reaction to 1033 surfactants used for hand washing; and 4) ps ychological stress and/or breach of confide n1034 tiality

for pregnancy

test results. These risks are minimized appropriately and are justified 1035Final Draft Document Dated December 8, 2010

Page 26 of 31 by the potential societal benefits, particularl y data on occupational exposure of agricu l1036 tural workers to pesticides during mixing and loading activities. 1037 1038

• The greatest risk to participants is that of heat

- related illness, given that the partic i1039 pants will be required to wear two lay ers of clothing during the scenario activities. 1040 This risk is lessened but not eliminated by the application of appropriate stopping 1041 rules (including cessation of all monitoring activities when the ambient heat

- index 1042 exceeds 105°F) and frequent monitoring of participants. Particip ants will be given 1043 frequent breaks, access to ample amounts of water or sports drinks, and educated 1044 about the dangers and s ymptoms of heat

- related illness. Appropriate medical man1045 agement procedures are also in place. 1046 1047

• The surrogate materials consist of four common pesticides: acephate, dithiopy r, i m1048 idacloprid, and thiophanate

- methyl. The participants will only be exposed to co n1049 centrations of the surrogate compound at accepted exposure thresholds. 1050 1051

• Participants will be selected from volunteers with experien ce handling these or si m1052 ilar compounds in WSP mixing and loading scenarios. Thus, all of the participants 1053 will have extensive experience in using these or similar products, and thus will be 1054 unlikely to misuse them in a way

that might increase their likelih ood of being acc i1055 dentally exposed. 1056 1057

• Participants will be reminded about safe handling practices and procedures, about 1058 wearing appropriate PPE, and will be monitored for any accidental or unintended 1059 product exposure. 1060 1061

• Allergic reactions to the surfactants u sed in hand washing are usually mild and eas i1062 ly

treated with over

- the

- counter steroidal creams. The study will exclude partic i1063 pants who have a history of severe skin reactions to such detergents. 1064 1065

• Minors and pregnant or lactating women are excluded from participation, with 1066 pregnancy either confirmed by

over- the

- counter pregnancy testing on the day

of 1067 study or b y opt

- out. The potential stigma resulting from study exclusion due to 1068 pregnancy is also appropriately

minimized. 1069 1070 Several members noted, however, that exposure to the surrogate chemicals is no longer 1071 listed as a potential risk to study participants in either the protocol or in the informed co n1072 sent documents. Study volunteers, it was argued, are likel y to handle these chemicals as 1073 part of their dail y ac tivities and the possibility of exposure is thus a risk of employ ment 1074 and not a risk of stud y participation. However, because of the nature of the study (inclu d1075 ing scripted handling of specific amounts of chemical), the Board felt that exposure to the 1076
surr ogate chemicals was a potential risk of study participation and recommended that the 1077 sponsor explicitly list this risk in the protocol and informed consent documents. 1078 1079

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Final Draft Document Dated December 8, 2010

Page 27 of 31 b. Vo luntary

and informed consent of all participants 1080 1081

• There is the possibility that th e participants in this study might represent particularly 1082 vulnerable populations, susceptible to coercion and undue influence. The study prot o1083 col, however, includes several mechanisms designed to minimize coercive recruitment 1084 and enrollment. 1085 1086

• Monetary comp ensation is not so high as to unduly influence participants. 1087 1088

• Spanish translations of the informed consent documents, informational packets, and r e1089 cruitment flyers were provided. Researchers will be working with local Spanish

1090 speaking community members to ensure that the appropriate regional dialect of Spanish 1091 is used (AHETF 2010d). 1092 1093 c. Equitable selection of study participants 1094 1095

• The study is designed to recruit an appropriatel y diverse population of participants who 1096 represent skilled agricultural workers in the five study locations. 1097 1098

• Community representatives and advocates are appropriately involved in the recruitment 1099 and enrollment of study participants. 1100 1101 2. The Board recommended that the study protocol be modified to address the concerns noted in 1102 the EP

A’ s Ethics Review (Evans and Sherman 2010b). In addition, the Board also raised the 1103 following concerns: 1104 1105

• The Board raised concerns that the revised water

- soluble packaging protocol was reviewed 1106 by

IIRB, Inc. using an expedited procedure. Future protocol revis ions that involve major 1107 changes like substitution of surrogate compounds and/or change in study site should be r e1108 viewed under full

- board procedures and reflected properl y in the IRB minutes. 1109 1110

• As noted above, the Board recommended that accidental exposure t o the surrogate chem i1111 cals be listed in the protocol and that the informed consent form also list surrogate exposure 1112 as a potential risk of study participation. 1113 1114

• The protocol excludes participants who normally wear additional personal protective 1115 equipment (such as chemical

- resistant clothing) that is not required by the chemical label 1116 and that might impact the objectives of the study . The Board recommended that this a s1117 sessment be done in a non

- directive way , so as not to encourage participants to wear less 1118 PPE than they would normally

in order to participate in the study

. 1119 1120

• Study participants will undergo hand washes prior to eating an ything, which will reduce 1121 their risk of accidental ingestion of the surrogate compounds. As man y of the adults in the 1122 U.S. sti ll smoke, however, the Board recommended that hand washes also occur before an y 1123 smoking break to further reduce their risk of accidental pesticide ingestion. 1124 1125Final Draft Document Dated December 8, 2010

Page 28 of 31 • The informed consent document states that “you may refuse medical treatment unless you 1126 get sick f

rom too much exposure to pesticides or from getting too hot, or if we believe you 1127
ar

e too sick to make a rational decision about getting medical tr eatment ” (Collier 2010b, 1128 emphasis added). Itwas unclear how this determination of rationality will be made, howe v1129
er. The protocol and informed consent document should be more explicit as to who will 1130 make this determination, and what criteria would be used. 1131 1132

• The Board raised some concerns about how the T ask Force plans to release individual e x1133 posure data to indiv idual study participants who request this information. For example, the 1134 Board encouraged the sponsor to consider how this information might be provided to par1135 ticipants who do not speak English and/or are illiterate. The Board also recommended that 1136 the requ est for individual study results be included as a check box on the informed consent 1137 document. The HSRB will be establishing a small working group to develop some gui d1138 ance for the Agency and sponsors regarding the release of individual exposure data to stud y 1139 participants. 1140 1141

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Final Draft Document Dated December 8, 2010

Page 29 of 31 REFERENCES 1142 1143 Agricultural Handler Exposure T ask Force (AHETF). 2010a. Supplemental 1 to the Backpack 1144 and Handgun Application of L iquid Spray s in Utilities Rights

- of

- Way Scenario Submission 1145 (AHE

- 400): SOPs Cited in AHE

- 400 ROW Submission. Un dated and unpublished document 1146 prepared b y the AHETF

. 1147 1148 AHETF . 2010b. Supplemental 2 to the Backpack and Handgun Application of L iquid Spray s in 1149 Utilities Rights

- of

- Way S cenario Submission (AHE

- 400): Providing Individual Exposure 1150 In formation to Subjects. Un dated and unpublished document prepared b y the AHETF

. 1151 1152 AHETF . 2010c. Supplemental 1 to the Revised Water Soluble Packet Mixer/L oader Scenario 1153 Submission (AHE

- 120): SOPs Cited in AHE

- 120 ROW Submission. Undated and unpublished 1154 document prepared b y the AHETF

. 1155 1156 AHETF . 2010d. Supplemental 2 to the Revised Water Soluble Packet Mixer/L oader Scenario 1157 Submission (AHE

- 120): Providing Individual Exposure Information to Subjects. Undated and 1158 unpublished document prepared b y the AHETF

. 1159 1160 Carley

, J.M. 2010. Ethics Review of Completed AEA TF II Mop Scenario W

orker Exposure 1161 Monitoring Study AEA

- 03. Dated October 4, 2010. Unpublished document prepared by the 1162 Of

fice of Chemical Safety

and Pollution Prevention, United States Environmental Protection 1163 Agency

. 1164 1165 Carroll, S. 2010. Ef ficacy Test Protocol: Field Efficacy T est of PMD and Lemongrass Oil Based 1166 Repellent ‘No Mas’A gainst Mosquitoes. Dated July 15, 2010. Unpublished document prepared 1167 by

Carroll

- Lo ye Biological Research. 1168 1169 Collier, C.H., for the Agricultural Handler Exposure Ta sk Force (AHETF). 2010a. Backpack and 1170 Handgun Application of Liquid Spray s in Utilities Rights

- of

- Wa y Scenario Submission (AHE

1171 400). Dated June 18, 2010. Unpublished document prepared b y the AHETF

. 1172 1173 Collier, C.H., for the Agricultural Handler Exposure T ask Force (AHETF). 2010b. Revised Water 1174 Soluble Packet Mixer/L oader Scenario Submission (AHE

- 120). Dated August 19, 2010. 1175 Unpublished document prepared b y the AHETF

. 1176 1177 EP

A Human Studies Review Board. 2008. April 9

- 10, 2008 Human Studies Review Board Mee t1178 ing Report. 1179 1180 EP

A Human Studies Review Board. 2009. June 24

- 25, 2009 Human Studies Review Board 1181 Meeting Report. 1182 1183 Evans, J., and K. Sherman. 2010a. Science and Ethics Review of AHE400: A New Scenario 1184 Design and Associated Protocol from the Agricultural Handler Exposure Ta sk Force (AHETF) 1185 Describing Proposed Research to Measure Dermal and Inhalation Exposure to Applicators Who 1186 Use Backpack or Hand Gun Spray ers to Appl y Pesticides in Utility Rights

- of

- Way. Dated 1187Final Draft Document Dated December 8, 2010

Page 30 of 31 September 30, 2010. Unpublished document prepared b y the Of fice of Chemical Safet y and 1188 Pollution Prevention, United States Environmental Protection Agency

. 1189 1190 Evans, J., and K. Sherman. 2010b. Science and Ethics Review of Revised AHETF Scenario D e1191 sign and Protocol AHE120 for Exposure Monitoring of W orkers during Mixing and L oading of 1192 Pesticide Products in Water Soluble Packets in Five Regions of the United States (August 2010). 1193 Dated October 1, 2010. Unpublished document prepared b y the Of fice of Chemical Safet y and 1194 Pollution Prevention, United States Environm ental Protection Agency

. 1195 1196 Fuentes, C., and K. Sherman. 2010. Science and Ethics Review of Protocol for Human Study of 1197 Mosquito Repellent Performance: Proposed Carroll

- Lo ye Field Ef ficacy T est of PMD and 1198 Lemongrass Oil

- Based Repellent ‘No Mas’ A gainst Mosqu itoes. Dated October 1, 2010. 1199 Unpublished document prepared b y the Of fice of Chemical Safet y and Pollution Prevention, 1200 United States Environmental Protection Agency

. 1201 1202 Independent Institutional Review Board, Inc. (IIRB, Inc.). 2010. Roster and Procedures. 1203 Unpublished materials prepared b y IIRB. 1204 1205 Johnson, D., for the Agricultural Handler Exposure Ta sk Force (AHETF). 2010a. Supplemental 3 1206 to the Backpack and Handgun Application of Liquid Spray s in Utilities Rights

- of

- Way Scenario 1207 Submission (AHE

- 400): Explanation of AHETF Spanish Tr anslation Project. Dated September 1208 30, 2010. Unpublished document prepared b y the AHETF

. 1209 1210 Johnson, D., for the Agricultural Handler Exposure Ta sk Force (AHETF). 2010a. Supplemental 3 1211 to the Revised W ater Soluble Packet Mixer/L oader Scenario Submission (AHE

- 120): 1212 Explanation of AHETF Spanish Tr anslation Project. Dated September 30, 2010. Unpublished 1213 document prepared b y the AHETF

. 1214 1215 Leighton, T . 2010. Science Review of the AEA TF II Mop Human Exposure Monitoring Stud y 1216 (AEA

- 03). MRID Numbers 48210201, 48231201, and 48231901 . Dated October 4, 2010. 1217 Unpublished document prepared b y the Of fice of Chemical Safet y and Pollution Prevention, 1218 United States Environmental Protection Agency

. 1219 1220 Selim, S., and M.N. Tayl or for the Antimicrobial Exposur e Assessment T ask Force II (AEA

TF 1221 II). 2010a. A Study for Measurement of Potential Dermal and Inhalation Exposure during 1222 Application of a Liquid Antimicrobial Pesticide Product Using Bucket and Mop Equipment for 1223 Cleaning Indoor Surfaces. Dated August 2, 20 10. Unpublished document prepared b y the 1224 AEA

TF II. MRID 48210201. 1225 1226 Selim, S., and M.N. Tayl or for the Antimicrobial Exposure Assessment T ask Force II (AEA

TF 1227 II). 2010b. Supplement 1 to A Stud y for Measurement of Potential Dermal and Inhalation 1228 Exposure during Application of a L iquid Antimicrobial Pesticide Product Using Bucket and Mop 1229 Equipment for Cleaning Indoor Surfaces. Dated September 15, 2010. Unpublished document 1230 prepared b y the AEA TF II. MRID 48231201. 1231 1232 Selim, S., and M.N. Tayl or for the Antimicrobi al Exposure Assessment T ask Force II (AEA

TF 1233

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Final Draft Document Dated December 8, 2010

Page 31 of 31 II). 2010c. Supplement 2 to A Stud y for Measurement of Potential Dermal and Inhalation 1234 Exposure during Application of a L iquid Antimicrobial Pesticide Product Using Bucket and Mop 1235 Equipment for Cleaning Indoor Surfaces. Dated September 21, 2010. Unpublished document 1236 prepared b y the AEA TF II. MRID 48231901. 1237 1238 Appendix 1 1239 1240 [to be added at a later date] 1241