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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

 WASHINGTON D.C., 20460 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION

4 Oct 2010 

MEMORANDUM 

SUBJECT: Ethics Review of Completed AEATF II Mop Scenario Worker Exposure 

Monitoring Study 

 

FROM: John M. Carley 

Human Research Ethics Review Officer 

Office of Pesticide Programs 

TO: Nader Elkassabany, PhD, Chief 

Risk Assessment and Science Support Branch 

Antimicrobials Division 

REF: Selim, S., and Taylor, M. (2010) A Study for Measurement of Potential 

Dermal and Inhalation Exposure During Application of a Liquid 

Antimicrobial Pesticide Product Using Bucket and Mop Equipment for 

Cleaning Indoor Surfaces. Unpublished study prepared by Golden Pacific 

Laboratories, LLC, under Project No. AEA03, Report No. 070265. 2116 

p. (MRID 48210201) 

Selim, S., and Taylor, M. (2010) A Study for Measurement of Potential 

Dermal and Inhalation Exposure During Application of a Liquid 

Antimicrobial Pesticide Product Using Bucket and Mop Equipment for 

Cleaning Indoor Surfaces: Supplement 1 to MRID 48210201. 

Unpublished study prepared by Golden Pacific Laboratories, LLC, under 

Project No. AEA03, Report No. 070265. 1146 p. (MRID 48231201) 

I have reviewed all available information concerning the ethical conduct of the 

research reported in the referenced documents, which describe the execution and results 

of a study in which dermal and inhalation exposure of professional janitorial workers to 

antimicrobial pesticides was monitored as they mopped indoor floors and disposed of the 

spent mop water. If it is determined to be scientifically acceptable, I find no barrier in 

regulation to EPA’s reliance on this study in actions under FIFRA or FFDCA.
Background and Chronology 

The scenario design and protocol for this study, identified by the investigators as 

Protocol #070265, was approved by the overseeing IRB and submitted to EPA for review 

in February 2008. The protocol and EPA’s review of 10 March 2008 were discussed by 

the HSRB on 9 April 2008. The HSRB review was generally favorable; their 25 June 

2008 final report of the April meeting concluded, with respect to ethics, that “if the 

proposed mop and wipe scenario design, protocol, and supporting documentation is revised 

as suggested in EPA’s review, the research would meet the applicable requirements of 40 

CFR part 26, subparts K and L.” 

Following the HSRB review, the protocol, consent form, and recruiting materials 

were extensively revised to address EPA, HSRB, and California DPR comments. The 

revised protocol was submitted to the IIRB, Inc., of Plantation FL on 26 February 2009, 

and approved, along with certified Spanish translations, on 16 March 2008. The 

approved English-language consent form is in the first supplement (S1:382-392)1, the 

Spanish-language consent form is at S1:442-454. A mark-up comparing the 26 Feb 09 

protocol and attachments to the proposal reviewed by EPA and the HSRB in April 2008 

appears at S1:6-159. 

After 16 March 2009 the protocol was amended seven times, with revised 

Consent Forms approved on 5 May 2009 (S1:573-596, used in monitoring in Cluster 1), 

and 21 Aug 2009 (S1:691-701, 722-732, used in monitoring at Clusters 2 and 3.) 

 Final approval of the protocol and supporting materials was granted by the 

California DPR on 17 April 2009. Subject recruitment began the following week on 24 

April 2009. Initial response was slow, and Amendment 3 (S1:601-601; approved 25 June 

2009) revised the recruiting procedures. Subject enrollment began on 1 July. Recruiting 

procedures were revised further to add recruiting by newspaper advertisements in 

Amendment 4 (S1:604-607; approved 13 July 2009.) Initial enrollment of subjects was 

completed on 24 July. 

After random assignment of enrolled subjects to specific monitoring slots at each 

of the three sites, subjects were monitored at site 1 from August 10-15; at site 2 from 

August 24-29, and at site 3 from September 28 through October 3. A more detailed 

chronology appears as Attachment 2 to this review. 

Scope of Review: 

This review reflects consideration of the primary study report and supplement 

cited above, and the following additional documents: 

 

1 Throughout this review page references to the primary submission, MRID 48210201, will be shown as 

(V1:nn), where ‘nn’ is the page number or page range within the 2116 pages of this document. References 

to Supplement 1, MRID 48231201, will be shown as (S1:nn), where nn refers to the page number or page 

range within the 1146 pages of that document. 

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• EPA’s 10 March 2008 Science and Ethics Review of the AEATF II Mop Scenario 

Design and Protocol 

• The HSRB’s 25 June 2008 report of its April 2008 discussion of the AEATF II 

Mop Scenario Design and Protocol 

• A spreadsheet “Subject Info all 32” submitted in response to EPA’s request on 30 

September, and appearing as Attachment 5 to this memo. 

Completeness of Submission: 

The checklist used by EPA to verify satisfaction of the requirements of §26.1303 

as they apply to the report of this research appears as Attachment 1 to this review. 

The initial report—MRID 48210201—was deficient in many ways. Appendix Q, 

containing IIRB Correspondence, spanned 1178 pages, entirely un-indexed, of which 

more than half contained irrelevant or redundant information. I noted the following 

major omissions from Appendix Q: 

• Documentation of IIRB extension of approval after Jan 09 

• Documentation of IIRB approval of revised protocol and supporting materials on 

16 Mar 09 

• Documentation of IIRB approval of translated materials on 3 Apr 09 

• Documentation of IIRB approval of Amendments 3, 4, and 5 

Appendix R, containing correspondence with the California DPR, was likewise 

un-indexed, with these major omissions: 

• Correspondence with CDPR before 29 Jan 09, including CDPR review of 1 Apr 

08 and GPL response 

• CDPR response to submission of 29 Jan 09 

• Documentation of CDPR final approval 

In addition, the chronology provided in Table 1 (V1:100) was significantly 

incomplete, and the changes made to the protocol, consent forms and other materials to 

address EPA and HSRB comments were not tracked. 

After being notified of these deficiencies by EPA, the AEATF corrected them 

with the submission of the cited supplement, MRID 48231201. It contains the protocol 

and supporting materials submitted to the IIRB on 26 Feb 09 tracking changes from the 

versions previously reviewed by EPA and the HSRB (S1:6-159), an expanded 

chronology (S1:160-162), and complete replacements for Appendices Q (S1:164-796) 

and R (S1:798-1116), correcting omissions, omitting redundant and irrelevant materials, 

and accompanied by indices based on those prepared by EPA in its initial review. 

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Much of the bulk in the correspondence files resulted from the failure of the 

investigators to maintain effective version control over the protocol, consent forms, and 

other documents, notwithstanding repeated requests from the IIRB to do so. 

No minutes of IIRB, Inc., meetings were submitted; because all IIRB, Inc. 

reviews subsequent to the HSRB meeting were conducted under expedited procedures, as 

noted in the letters of approval, no minutes were taken under IIRB’s procedures. In 

addition, neither the IIRB, Inc., roster nor the IIRB, Inc., procedures were submitted as 

part of the study. 

Protocol Amendments: 

 Subsequent to IIRB approval of the revised protocol on 16 Mar 09 it was 

amended 7 times. A summary of the scope of all amendments appears as Attachment 3 

to this review. Although Amendment 2 made minor adjustments in some procedures, 

Amendments 3 and 4 are of primary ethical interest. Both resulted from the discovery in 

the field that the planned approach to recruitment—approaching janitorial service 

providers and asking to post flyers in their premises—was unproductive. Revised 

procedures in Amendment 3 allowed enrollment of individual qualified candidates before 

the entire group had been identified, and Amendment 4 provided for recruiting through 

newspaper advertising. The choice of newspapers—three in all, each serving a different 

community in the Fresno area—was appropriate. 

 

Protocol Deviations: 

 

Two reports of protocol deviations were made to the IIRB, Inc. after completion 

of the research; they are also summarized in Attachment 3. Two points raised in 

Deviation Report 1 (V1: 1731-1736) are of potential ethical interest. Most subjects 

reportedly declined to take rest breaks, or took less than the 10 minutes provided for in 

the protocol, and at one monitoring site photographs were taken showing subjects’ faces. 

No images of subjects’ faces were included in the report. In my judgment neither of 

these deviations affected either data quality or subject safety. 

The demographic data shows what may have been another, unacknowledged 

deviation, in that two enrolled subjects (#8, who was monitored in cluster 2, and #5, an 

alternate) reported their general health as only “fair”. The protocol (§9.3.1, V1:384) 

specifies that to be included subjects must be “in good health.” The consent form 

(V1:419) states that participants “must be healthy adults.” The “Subject Self-Reporting 

Demographic Form,” Appendix D to the protocol (V1:430) offered candidates a choice in 

describing their health as ‘Excellent,’ ‘Good,’ ‘Fair,’ or ‘Poor.’ The decision to enroll 

subjects in only ‘fair’ health is not explained. 

Recruiting: 

The initial design of the recruiting process relied on flyers, posted in the 

workplaces of janitorial services providers who agreed to do so after discussing the 

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research with the investigators. This process was attempted, but proved unproductive. 

Very few service providers were willing to post flyers, and very few candidates 

responded to the few that were posted by calling the investigators for more information. 

A few candidates did respond, but the protocol did not provide for enrolling them until 

after the full complement had been recruited and randomized; the investigators were 

concerned that they would lose contact with these candidates. After discussion with 

EPA, the investigators put forward Amendment 3, which permitted them to inform, 

consent, and enroll subjects as they came forward, and randomly assign them to 

monitoring sites and slots (M1-M6 at each site) after recruiting was completed. EPA 

endorsed this revision to the original plans for recruiting and randomization. 

 Response to the recruiting flyers continued slow, and after further discussion with 

EPA, the investigators put forward Amendment 4, to allow recruiting through newspaper 

advertisements. This change—and newspaper advertisements in English and Spanish— 

was approved by the IIRB, Inc. in mid July, and recruiting was completed on July 24. 

 No demographic information was provided about the subjects in the primary 

study report or supplement. In response to an EPA request, a spreadsheet was provided 

on 30 September 2010 reporting subject characteristics. The full spreadsheet appears as 

Attachment 5 to this review; its content is summarized in Table 1 below. 

Table 1: AEATF II Mop Study Subject Characteristics 

All Enrolled Subjects Monitored Subjects Alternate Subjects 

Male 15 10 5 

Female 17 8 9 

English 20 11 9 

Spanish 12 7 5 

Range of Experience 3 mos – 40 yrs† 3 mos – 40 yrs 1 – 20 yrs 

Mean Years Experience 8.8 yrs 11.1 yrs 5.8 yrs 

Age Range 18 - 53 18 - 53 18 - 50 

Mean Age 36.8 yrs 38.1 yrs 35.3 yrs 

Health ‘Excellent’ 18 10 8 

Health ‘Good’ 12 7 5 

Health ‘Fair’ 2 1 1 

Requested Results 25 (78%) 15 (83%) 10 (71%) 

† Experience was not reported for subject #30 (alternate; dropped because she moved away) 

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Actual monitoring was conducted without noteworthy incident. No subjects 

withdrew from the research. No adverse events or other incidents of concern were 

reported. 

Applicable Ethical Standards 

Because this study was initiated after 7 April 2006, prior submission of the 

protocol and supporting materials to EPA was required by 40 CFR §26.1125. 40 CFR 

§26.1601(c) required EPA to review the protocol and present it to the HSRB for review. 

These requirements were satisfied. 

EPA Protocol Review Comments 

In its Science and Ethics review of 10 March 2008 EPA noted “the following 

specific [ethical] deficiencies should be corrected before the research is initiated: 

• Better provision is need for ensuring that Spanish-speaking candidates are fully 

informed and fully comprehend what they have been told. It would be better for 

candidate interviews to be conducted by a member of the research team fluent in 

Spanish than to rely on a translator. 

• References in the consent forms to “normal business hours” should be replaced by 

references expressed in California local time, and care must be taken to ensure 

that a Spanish-speaking responder can be reached at any telephone number cited 

as a source for further information.” 

In the revisions submitted to the IIRB, Inc. on 26 February 2009, all references in 

protocol and consent form to translators were replaced by references to researchers fluent 

in Spanish, to whom the recruiting and consenting responsibilities of the PI would be 

delegated when candidates preferred to interact in Spanish. The Consent Form and 

California Experimental Subject’s Bill of Rights were revised to show hours for calling in 

Pacific (local) time. 

HSRB Protocol Review Comments 

In its 25 June 2008 report of its April 2008 discussion of the AEATF Mop and 

Wipe Scenarios the HSRB summarized its recommendations as follows: 

“The Board concurred with the initial assessment of the Agency that if the proposed 

mop and wipe scenario design, protocol, and supporting documentation is revised as 

suggested in EPA’s review, the research would meet the applicable requirements of 

40 CFR part 26, subparts K and L.” 

In addition, the HSRB made several specific suggestions for refinements; a 

summary of these suggestions, and of how they were addressed by the AEATF, appears 

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as Attachment 4 to this review. Most were addressed responsively by the investigators, 

some less responsively, and some were not addressed. 

 One HSRB comment observed that “although the risks to subjects from exposure 

to the test compound appear very low, . . . it might be possible to design scenarios in 

which instead of an antimicrobicide, some less toxic tracer substance might be used. It 

would be appropriate for protocols to discuss this possibility for further minimizing 

risks.” EPA agrees that it might be possible to design studies using tracers, but disagrees 

that it would be appropriate for AEATF II protocols to discuss this possibility. EPA has 

accepted the approach defined in the AEATF II Governing Document, which relies on 

exposure monitoring with registered antimicrobial products used in approved use 

patterns. EPA believes that tracer studies would be likely to raise more new issues, 

including issues of safety, than studies with registered antimicrobials. 

Regulatory and Statutory Standards 

The following provisions of 40 CFR 26 Subpart Q, as amended effective August 

22, 2006, define the applicable ethical standards, which read in pertinent part: 

§26.1703: Except as provided in §26.1706, . . . EPA shall not rely on data from 

any research involving intentional exposure of any human subject who is a 

pregnant woman (and therefore her fetus), a nursing woman, or a child. 

§26.1705: Except as provided in §26.1706, . . . EPA shall not rely on data from 

any research initiated after April 7, 2006, unless EPA has adequate information 

to determine that the research was conducted in substantial compliance with 

subparts A through L of this part. . . . 

In addition, §12(a)(2)(P) of the Federal Insecticide, Fungicide and Rodenticide 

Act (FIFRA) applies. This passage reads: 

In general, [i]t shall be unlawful for any person . . . to use any pesticide in tests 

on human beings unless such human beings (i) are fully informed of the nature 

and purposes of the test and of any physical and mental health consequences 

which are reasonably foreseeable therefrom, and (ii) freely volunteer to 

participate in the test. 

Findings 

Responsiveness to EPA and HSRB reviews 

EPA’s comments were satisfactorily addressed, as were most of the HSRB’s 

comments, in the revisions approved by the IIRB on 16 March 2009. 

Prohibition of research involving intentional exposure of pregnant or nursing women 

or of children 

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All enrolled subjects were at least 18 years old. All female subjects, regardless of 

age, self-administered over-the-counter pregnancy tests on the day of monitoring; all such 

tests were negative. The prohibition in 40 CFR §26.1703 of research involving 

intentional exposure of pregnant or nursing women or of children under 18 was satisfied. 

Substantial compliance with 40 CFR 26 subparts A through L 

40 CFR §26.1705 requires that EPA have “adequate information to determine that 

the research was conducted in substantial compliance with subparts A through L of this 

part.” Within this range, only subparts K and L are directly applicable to the conduct of 

third-party research. 

Notwithstanding initially poor documentation of the interaction of the 

investigators and the overseeing IRB, and the failure of the investigators to address all the 

points raised by the HSRB in its review of the proposal, I identified no noteworthy 

deficiencies in the ethical conduct of the research. The protocol was faithfully executed, 

properly amended when necessary, and all amendments were approved by the overseeing 

IRB before they were implemented. The deviations reported are of the nature to be 

expected in complicated field research of this kind, and did not affect the welfare or 

safety of the subjects, or compromise their informed and voluntary consent. 

Taking into account the overall care with which the research was defined and 

conducted, these minor deficiencies in the conduct and documentation of the research fall 

far below the level of substantial non-compliance with subparts A through L of 40 CFR 

part 26. I conclude that 40 CFR §26.1705 does not prohibit EPA reliance on this study. 

Compliance with 40 CFR §26 subpart M 

As is documented in Attachment 1 to this review, taking into account both the 

primary study report (MRID 48210201) and the supplement (MRID 48231201), the 

central requirements of 40 CFR §26 subpart M, §26.1303 to document the ethical 

conduct of the research were addressed. The failure to provide minutes of IIRB, Inc., 

meetings, the IIRB roster and IIRB procedures did not compromise this review. Taking 

the two submissions together, along with the separately submitted roster and procedures 

of the IIRB, Inc., the requirements of 40 CFR §26.1303 were satisfactorily addressed. 

• Compliance with FIFRA §12(a)(2)(P) 

The requirement of FIFRA §12(a)(2)(P) that human subjects of research be “fully 

informed of the nature and purposes of the test and of any physical and mental health 

consequences reasonably foreseeable therefrom,” and “freely volunteer to participate in 

the test,” was met for this study. 

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Page 9 of 18 

Conclusions 

This study reports research conducted in substantial compliance with the 

requirements of 40 CFR 26 subparts A through L. In its conduct it met all applicable 

ethical standards for the protection of human subjects of research. Initially deficient 

reporting was promptly corrected, and all requirements for documentation of ethical 

conduct of the research were satisfied. If this study is determined to be scientifically 

valid and relevant, there is no regulatory barrier to EPA’s reliance on it in actions under 

FIFRA or §408 of FFDCA. 

Attachment 1: §26.1303 completeness check for AEATF Mop Scenario Report 

Attachment 2: Chronology of AEATF Mop Study 

Attachment 3: Summary of Amendments and Deviations to AEATF Mop Study 

Attachment 4: Responsiveness of AEATF to HSRB Comments on Mop Study 

Attachment 5: GPL Spreadsheet: “Subject Info All 32” 
Attachment 1 

§ 26.1303 Check for Completeness of Reports of Human Research Submitted for EPA Review 

AEATF II Mop Scenario Report: MRIDs 48210201, 48231201, and 48231901

Page 10 of 18 

Any person who submits to EPA data derived from human research covered by this subpart shall provide at the time of submission 

information concerning the ethical conduct of such research. To the extent available to the submitter and not previously provided to 

EPA, such information should include: 

Requirement Y/N Comments/Page References 

§1115(a)(1): Copies of 

• all research proposals reviewed, 

• scientific evaluations, if any, that accompany the proposals, 

• approved sample consent documents, 

• progress reports submitted by investigators, and reports of injuries to 

subjects. 

Y 

n/a 

Y 

Y 

Initially addressed in protocol; 

Amend. 1 (S1:525-527) 

Amend. 2 (S1:528-532) 

Amend. 3 (S1:601-602) 

Amend. 4 (S1:604-607) 

Amend. 5 (S1:633-636) 

Amend. 6 (S1:771-772) 

Amend. 7 (S1:642-643) 

Approved English CFs: 

 3/16/09 (S1:382-392) 

 5/5/09 (S1:573-583) 

 8/21/09 (S1:691-701) 

Approved Spanish CFs: 

 3/16/09 (S1:442-454) 

 5/5/09 (S1:584-596) 

 8/21/09 (S1:722-732) 

Progress Rpt (S1:173-177) 

§1115(a)(2): Minutes of IRB meetings which shall be in sufficient detail to show 

• attendance at the meetings; 

• actions taken by the IRB; 

• the vote on these actions including the number of members voting 

for, against, and abstaining; 

• the basis for requiring changes in or disapproving research; 

• a written summary of the discussion of controverted issues and their 

resolution. 

N All post-HSRB IIRB reviews were 

under expedited procedures; no 

minutes were made. 

§1115(a)(3): Records of continuing review activities. Y S1:171, 735, 796 

§1115(a)(4): Copies of all correspondence between the IRB and the investigators. Y S1:163-796; V1:584-1760 

§1115(a)(5): 

• A list of IRB members identified by name; earned degrees; representative 

capacity; indications of experience such as board certifications, licenses, 

etc., sufficient to describe each member’s chief anticipated contributions 

to IRB deliberations; 

• any employment or other relationship between each member and the 

institution, for example, full-time employee, a member of governing panel 

or board, stockholder, paid or unpaid consultant. 

N Already available to EPA 

§1115(a)(6): Written procedures for the IRB in the same detail as described in § 

26.1108(a) and § 26.1108(b). N Already available to EPA 

(a) Copies of all of the records relevant to the research specified by §26.1115(a) to be prepared and 

maintained by an IRB 

§1115(a)(7): Statements of significant new findings provided to subjects, as 

required by § 26.1116(b)(5). n/a 

(1) The potential risks to human subjects; Y Addressed in protocol; slightly 

revised S1:17 

(2) The measures proposed to minimize risks to the human subjects; Y Addressed in protocol 

(3): The nature and magnitude of all expected benefits of such research, 

and to whom they would accrue; Y Addressed in protocol 

(4) Alternative means of obtaining information comparable to what would 

be collected through the proposed research; and Y Addressed in protocol 

(b) Copies of all of 

the records relevant 

to the information

§1125(a) 

A discussion of: 

(5) The balance of risks and benefits of the proposed research. Y Addressed in protocol 
Attachment 1 

§ 26.1303 Check for Completeness of Reports of Human Research Submitted for EPA Review 

AEATF II Mop Scenario Report: MRIDs 48210201, 48231201, and 48231901

Page 11 of 18 

Requirement Y/N Comments/Page References 

§1125(b): All information for subjects and written informed consent agreements as 

originally provided to the IRB, and as approved by the IRB. Y 

Provided CFs S1:245-256; 325-

336; 365-375; 419-431; 484-495; 

504-514; 658-668; 705-717 

Approved Engl CFs S1:382-392; 

573-583; 691-701 

Approved Span. CFs S1:442-454; 

584-596; 722-732 

§1125(c): Information about how subjects will be recruited, including any 

advertisements proposed to be used. Y Initially satisfied in protocol. 

Flyers & Ads in Engl & Span 

§1125(d): A description of the circumstances and methods proposed for 

presenting information to potential human subjects for the purpose of obtaining 

their informed consent. 

Y Initially satisfied in protocol; see 

also amendments 3 and 4 

§1125(e): All correspondence between the IRB and the investigators or sponsors. Y See §1115(a)(4) above 

§1125(f): Official notification to the sponsor or investigator, in accordance with the 

requirements of this subpart, that research involving human subjects has been 

reviewed and approved by an IRB. 

Y 

IRB approvals 

 Renewal S1:183 

 3/16/09 S1:381; 394-395; 438 

 5/5/09 S1:559; 566; 572 

 Amend 3 6/25/09 S1:610 

 Amend 4 7/10/09 S1:616 

 Amend 5 7/27/09 S1:637 

 8/21/09 S1:690 

 Amend 6 5/25/10 S1:774 

Final CDPR approval S1:1145-46 

(c) Copies of sample records used to document informed consent as specified by 

§26.1117, but not identifying any subjects of the research Y S1:739-760 

(d) If any of the information listed in paragraphs (a) through (c) of this section is not 

provided, the person shall describe the efforts made to obtain the information. n/a 
Attachment 2 

Chronological Listing of Events: AEATF Mop Study 

Based on Table 1 (V1:100) and Supplemental Chronology (S1:161-162) 

Page 12 of 18 

14 Jan 08 GPL submission of undated protocol and supporting materials to IIRB for review 

16 Jan 08 Submission of ICF to CDPR 

18 Jan 08 GPL resubmission of protocol with (erroneous) version date of 16 Jan 07 and undated supporting 

materials 

22 Jan 08 IIRB approval of protocol and supporting materials 

14 Feb 08 CDPR reviewed ICF submitted on 16 Jan 08 and provided summary of revisions to GPL 

25 Feb 08 Submission of IIRB-approved protocol to EPA 

10 Mar 08 EPA Science & Ethics Review of Proposal 

9 Apr 08 HSRB Discussion of Proposal 

11 Apr 08 CDPR review calling for revisions in protocol and ICF submitted on 16 Jan 08 

25 Jun 08 HSRB Final Report of April public meeting 

12 Jan 09 GPL submission of annual progress report to IIRB 

21 Jan 09 IIRB extension of approval through 19 Jan 10 

27 Jan 09 GPL submission of responses to CDPR review of 11 Apr 08 

19 Feb 09 CDPR provisional approval of study 

23 Feb 09 Start of search for test site selection 

26 Feb 09 GPL submission of undated revised protocol and supporting materials to IIRB, with extensive 

changes from version of Jan 08 not characterized or tracked 

3 Mar 09 GPL resubmission of 22 Jan 08 IIRB-approved CF with tracked changes 

16 Mar 09 GPL resubmission of protocol with revised title page incorporating version date of 26 Feb 09 and 

revised total page count 

16 Mar 09 IIRB approval of revised protocol, CF, and other materials. 

8 Apr 09 Study Initiation (V1:6) [Date on which SD /s/ protocol] 

17 Apr 09 CDPR final approval of study 

24 Apr 09 Start of subject recruitment 

4 May 09 GPL submission of protocol Amendments 1 and 2 

5 May 09 IIRB approval of revised protocol, protocol Amendments 1 and 2, and CF, recruiting flyer, and 

recruiting scripts in English and Spanish 

24 Jun 09 GPL submission of Amendment 3 to IIRB. 

25 Jun 09 IIRB approval of Amendment 3 

1 Jul 09 Start of subject enrollment 

9 Jul 09 GPL submission of Amendment 4 and English/Spanish recruiting ads to IIRB 

10 Jul 09 IIRB approval of Amendment 4 

13 Jul 09 IIRB approval of English/Spanish recruiting ads 

24 Jul 09 End of subject enrollment 

27 Jul 09 GPL submission of Amendment 5 to IIRB 

27 Jul 09 IIRB approval of Amendments 5 
Attachment 2 

Chronological Listing of Events: AEATF Mop Study 

Based on Table 1 (V1:100) and Supplemental Chronology (S1:161-162) 

Page 13 of 18 

27 Jul 09 Start of analytical work: preparation of analytical standards and laboratory fortification solutions 

27 Jul 09 Secured Cluster 1 test site at former IRS office building 

29-30 Jul 09 Preparation of field fortification solutions 

10-15 Aug 09 Cluster 1 exposure monitoring at IRS office building 

10 Aug 09 First subject ME M5 enrolled/monitored; “Experimental Start” (V1:6) 

11 Aug 09 ME M6; field fortifications 

11 Aug 09 Analyses started for subject and field fortification samples 

12 Aug 09 ME M2 

13 Aug 09 ME M3; field fortifications 

14 Aug 09 ME M4 

15 Aug 09 ME M1; field fortifications 

17 Aug 09 Secured Cluster 2 test site at vacant Rite Aid retail building 

21 Aug 09 GPL submission of Amendment 7 to IIRB 

21 Aug 09 IIRB approval of Amendment 7 

21 Aug 09 IIRB email reference to approval of revised CFs and supporting materials 

24-29 Aug 09 Cluster 2 exposure monitoring at Rite Aid retail building 

24 Aug 09 ME M6 

25 Aug 09 ME M5; field fortifications 

26 Aug 09 ME M4 

27 Aug 09 ME M3; field fortifications 

28 Aug 09 ME M2 

29 Aug 09 ME M1; field fortifications 

8 Sep 09 Secured Cluster 3 test site at Retired Teacher’s Education Center 

28 Sep- 

 3 Oct 09 Cluster 3 exposure monitoring at Retired Teacher’s Education Center 

28 Sep 09 ME M6 

29 Sep 09 ME M5; field fortifications 

30 Sep 09 ME M4 

1 Oct 09 ME M3; field fortifications 

2 Oct 09 ME M2 

3 Oct 09 ME M1; field fortifications; last subject monitored 

13 Nov 09 Analyses completed for subject and field fortification samples (p. 100) 

15 Jan 10 GPL submission of closeout report to IIRB 

29 Jan 10 IIRB acceptance of closeout report 

2 Mar 10 “Experimental Termination” (V1:6) “Last day of data collection” (V1:100) 

20 May 10 GPL submission of Amendment 6 to IIRB 
Attachment 2 

Chronological Listing of Events: AEATF Mop Study 

Based on Table 1 (V1:100) and Supplemental Chronology (S1:161-162) 

Page 14 of 18 

24 May 10 IIRB acceptance of Amendment 6 

4 Jun 10 GPL submission of Deviation Report 1 to IIRB 

4 Jun 10 IIRB acceptance of Deviation Report 1 

28 Jul 10 GPL submission of Deviation Report 2 to IIRB 

28 Jul 10 IIRB acceptance of Deviation Report 2 

28 Jul 10 “Study Completion” (V1:6) 

2 Aug 10 Informal Submission of “Final Report” to EPA 

31 Aug 10 Formal Submission of “Final Report” to EPA 

20 Sep 10 Formal Submission of Supplement 1 to EPA 

21 Sep 10 Formal Submission of Supplement 2 to EPA
Attachment 3 

Summary of Amendments and Deviations 

AEATF-II Mop Study GPL Protocol # 070265 

Page 15 of 18 

Amendment 1: (May 2009; S1:525-527) 

• Incorporated minimum size of 10K sq ft in definition of acceptable sites 

• Permitted use of “non-vacant” meeting spaces for hire 

• Adds provision to send copy of flyer to employers before decision about posting 

Amendment 2: (May 2009; S1:528-532) 

• Clarified that CF would be available in either English or Spanish 

• Added commitment to make MSDS available in both English and Spanish 

• Clarified when SD would notify local sewer authority of intended flushing of waste 

• Clarified that at least 7 days would elapse between monitoring at different clusters 

• Clarified that all recruiting materials and communication with subjects would be 

available in either English or Spanish 

• Clarified availability of 24-hr toll-free answering service in both English and Spanish 

• Committed to provide each subject with a copy of the label and MSDS 

• Harmonized descriptions of recruiting procedures in sections 9.1.2 and 9.3 

• Reflected name change of Grayson Research in exclusion criteria 

• Changed study procedures: 

o To permit discussion with subjects either individually or in a group 

o To specify removal of shoes before removal of pants 

• Clarified procedure for weighing buckets of mop solution 

• Clarified collection of sock dosimeters before WBDs 

• Revised reference to SOP 

• Clarified reporting of weights of buckets and mop solution 

• Deleted unnecessary reference to QAU statements 

• Reflected name change of Grayson Research throughout protocol 

Amendment 3: (June 24, 2009; S1:601-602) 

• Revised procedures in recruitment phase 

Amendment 4: (July 9, 2009; S1:604-607) 

• Added newspaper advertisements (English and Spanish) to recruiting process 

Amendment 5: (July 27, 2009; S1:633-636) 

• Revised method for assigning subjects to ME slots 

• Corrected reference to SOP 

• Revised §10.4 Re: Field Recovery Evaluation to be consistent with revised SOP 
Attachment 3 

Summary of Amendments and Deviations 

AEATF-II Mop Study GPL Protocol # 070265 

Page 16 of 18 

Amendment 6: (August 4, 2009; S1:771-772) 

• Further revised §10.4 Re: Field Recovery Evaluation 

• Revised §12.2 Re: Analytical Method 

Amendment 7: (August 21, 2009; S1:642-643) 

• Changed Field Study Coordinator and Field Study Associate 

Deviation Report 1: (May 25, 2010; V1:1731-1736) 

• Subjects washed hands with 50% IPA and water as well as with soap before monitoring 

• Light readings were not taken at monitoring sites as called for in the protocol 

• Subjects declined to take breaks at 30-minute intervals or took less than 10 minute breaks 

• Subject face/neck wipe samples at sites 2 and 3 not collected as specified 

• Environmental measurements made less frequently than specified at site 1 

• One environmental data logging device failed to record humidity 

• Field fortification samples of hand wash at site 1 not collected at all prescribed times 

• Air pump flows improperly recorded for subjects M5 and M6 at site 1 

• Air pump calibration data for 11 Aug 09 lost 

• Two subjects mopped a few minutes over or under allotted time 

• Air pumps malfunctioned in two instances 

• Two sites had less floor area than specified in protocol 

• On one day, photographs included faces of subjects 

• Temperature of walk-in cold locker in which samples were stored was not confirmed at 

site 2 

• One subject mopped the same area twice during the same ME, after mopping all available 

floors 

• Air pump ID not recorded for one ME; could not be linked to calibration data 

• OVS tubes fortified at field site vice lab at site 2 

• Background air samples at site 3 collected at 3 ft vice 5 ft above floor 

Deviation Report 2: (July 13, 2010; V1:1754-1755) 

• Some sample fortifications were at incorrect levels 

• Solvent blanks were not injected before all analytical runs as specified
Attachment 4 

Responsiveness to HSRB Comments 

AEATF-II Mop Study GPL Protocol # 070265 

Page 17 of 18 

HSRB Comment Response 

Although the risks to subjects from exposure to 

the test compound appear very low, . . . it might 

be possible to design scenarios in which instead 

of an antimicrobicide, some less toxic tracer 

substance might be used. It would be 

appropriate for protocols to discuss this 

possibility for further minimizing risks. 

EPA believes tracer studies would raise 

more new issues, including issues of 

safety, than studies with registered antimicrobials used in approved use 

patterns. 

[T]he requirement for females under the age of 

50 to take a pregnancy test could be refined. It 

would be possible to design criteria that created 

a better fit between which female subjects 

might be able to get pregnant, and which of 

them are being asked to take that test. By doing 

this, the researchers would be showing greater 

respect for this group of subjects. 

Amended to require ALL females, 

regardless of age, to take pregnancy 

test. Investigators explained to EPA 

that they thought it would be less 

intrusive and more respectful to apply 

the requirement to all women than to 

inquire about their individual ability to 

become pregnant. 

Protocol 

[P]rovide a greater justification for why 

subjects older than 65 are excluded. 

“Because this study may require 

physically strenuous activities, an upper 

age limit was imposed” (S1:31) 

[M]ake sure that the consent forms are at an 

appropriate level of readability. . . . [T]here 

appears to be room for further simplification. 

Negligible change (from 9.9 to 9.8) in 

reading level (Flesch-Kincaid Grade 

Level for CF.) F-KGL for some 

amended material is as high as 16+. 

[The consent form does not] describe 

adequately the procedures discussed in the 

protocol relating to (a) still photography of the 

subjects, (b) videotaping of the subjects, and (c) 

observation of the subjects by members of the 

study team. 

Changed to state that photos and video 

will be taken by an assigned observer, 

and that subjects’ faces will not be 

shown in any reports. “There were 

always 3 to 4 study personnel following 

the subject during a ME.” (V1:38) 

[E]xplain [in CF] that the underlying purpose of 

the study will be to collect information that will 

be provided to the EPA, and that the EPA 

would use that information to determine the 

appropriate standards for allowable exposures 

to products such as the test compound. 

Not addressed 

Replace the confusing term “same-sex person” 

in procedure step 4 in CF; replace with the 

descriptions used elsewhere in the form, such as 

“a researcher of your own sex.” 

“same-sex member of the research 

team” unchanged. Two other 

references to a “researcher of your own 

sex” changed to “researcher of your 

own gender.” 

Explain any known risks to subjects, such as 

eye irritation. 

“Permanently” changed to “forever” in 

CF discussion of risk of eye irritation 

Consent Form 

Correct garbled sentence in IIRB-approved CF 

concerning risks to the unborn; Explain origin 

of garble not initiated by investigators. 

Garble not present in post-HSRB CFs. 

Source of earlier garble not explained. 
Attachment 4 

Responsiveness to HSRB Comments 

AEATF-II Mop Study GPL Protocol # 070265 

Page 18 of 18 

HSRB Comment Response 

Explain in flyer that research will measure 

inhalation as well as dermal exposure 

Not changed (S1:82) 

Correct garbled eligibility criterion in Flyer Corrected (S1:82) 

Recruiting 

Flyer 

Correct mischaracterization of how EPA will 

use the resulting data 

Corrected (S1:82) 

Add reference to inhalation monitoring in 

phone dialogs 

Already included in phone dialog; no 

change required 

Provide more detail about how community—

including unions—will be engaged/involved 

Revised in protocol (S1: 19) and in 

Appendix H (S1:87). Intention was to 

engage unions through pre-recruiting 

employer meetings, none of which took 

place. 

Other 

Ensure appropriate dialect is used in 

translations, and clarify who is doing 

translations 

Translations done by CA translator, 

who was part of research team. 

Protocol states “all documents . . . will 

be translated by an individual familiar 

with idioms and common dialects used 

in the Fresno area.” (S1:29)