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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON D.C., 20460

OFFICE OF

CHEMICAL SAFETY AND

POLLUTION PREVENTION

March 20, 2014 

MEMORANDUM

SUBJECT: Materials for Review by the Human Studies Review Board for its 

 April 8-9, 2014 Meeting

TO: Jim Downing 

 Designated Federal Official 

 Human Studies Review Board 

 Office of Science Advisor (8105R) 

FROM: William L. Jordan 

 Deputy Director 

 Office of Pesticide Programs (7501P) 

This memorandum describes the materials that the Environmental Protection Agency’s 

(EPA’s) Office of Pesticide Programs is providing for review by the Human Studies Review 

Board (HSRB or Board) at the meeting scheduled for April 8-9, 2014. At this meeting, EPA will 

ask the Board to address scientific and ethical issues surrounding these four topics, each of which 

is discussed further below: 

1. A new scenario design and associated protocol from the Antimicrobial Exposure 

Assessment Task Force II (AEATF-II) describing proposed research to monitor dermal 

and inhalation exposure during manual pouring of solid formulation antimicrobial 

products.1

 

2. A new scenario design and associated protocol from the AEATF-II describing proposed 

research to monitor dermal and inhalation exposure during application of latex paint 

containing an antimicrobial pesticide product using brush and roller equipment. 

3. A new protocol from the AEATF-II describing proposed research to measure the removal 

efficiency of 1,2-Benzisothiazol-3(2H)-one (known as BIT) from hand surfaces using an 

isopropyl alcohol/water wipe and wash procedure. 

 

1

 This topic was originally scheduled for review by the HSRB on October 1, 2013, but that meeting was cancelled as 

a result of the federal government shutdown that occurred from October 1-16, 2013. 
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4. A new protocol from the U.S. Department of Agriculture describing proposed research to 

determine the bite protection level of repellent-treated clothing for the United States 

Military 

In addition to presenting its reviews of the four topics listed above, the EPA will also present 

background information about EPA’s Repellency Awareness Program and discuss potential 

implications for the HSRB. No background documents are being provided on this topic, and there are 

no charge questions for consideration by the Board. The Agency expects to provide its presentation 

to the Board members in advance of the meeting. 

1. AEATF II Protocol – Manual Pouring of Solid Formulation: 

First, the Board will consider a new scenario design and associated protocol from the 

Antimicrobial Exposure Assessment Task Force II (AEATF-II) describing proposed research to 

monitor dermal and inhalation exposure during manual pouring of solid formulation 

antimicrobial products. Because the proposed research involves scripted exposure, it meets the 

regulatory definition of “research involving intentional exposure of a human subject” and thus is 

covered by subparts K and L of EPA’s amended rule for the protection of human subjects of 

research. The rule at 40 CFR §26.1125 requires a sponsor or investigator to submit to EPA, 

before conducting a study involving intentional exposure of human subjects, the protocol and 

related materials describing the proposed human research. In addition, EPA’s regulation at 40 

CFR §26.1601 requires EPA to perform science and ethics reviews of the submitted proposal and 

to seek HSRB review of the proposed research. EPA has reviewed the scenario design and 

protocol, and has concluded that the research, with minor revisions, is likely to generate 

scientifically sound, useful information and to meet the applicable provisions of the EPA 

regulations in 40 CFR part 26, subparts K and L. The charge questions and documents being 

transmitted to the HSRB for review are listed below. 

Charge Questions for AEATF-II Protocol:

If the AEATF-II study proposal AEA07 is revised as suggested in EPA’s review and if the 

research is performed as described: 

1. Is this research is likely to generate scientifically reliable data, useful for assessing the 

exposure of those who pour solid formulation antimicrobial pesticide products 

2. Is the research likely to meet the applicable requirements of 40 CFR part 26, subparts K and 

L? 

Documents for AEATF-II Solid Pour Protocol Review: 

EPA is providing for HSRB review the following 9 files concerning the AEATF-II protocol 

AEA07. These files were released in September 2013, in preparation for the HSRB meeting on 

October 1, 2013. The files are being re-released at this time, for the convenience of the HSRB 

members. 
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a. EPA Science and Ethics Review of AEATF-II Solid Pour Scenario Design and 

Protocol for Exposure Monitoring (dated September 10, 2013) 

b. Volume 1: AEATF-II Pour Solid Protocol Submission 

- AEATF-II’s Transmittal Letter 

- 40 CFR 26.1125 Checklist 

- Pour Solid Study Design Document 

c. Volume 2: AEATF-II Pour Solid Protocol Submission 

- Study Protocol Dated 4/26/13, Approved 4/29/13 

- Approved Occupational Monitoring Informed Consent Form Dated 4/29/13 

- Approved Residential Monitoring Informed Consent Form Dated 4/29/13 

- Approved Spanish Translation of Informed Consent Forms dated 4/29/13 

- Approved Recruitment Materials Dated 5/1/13 

- Approved Spanish Translation of Recruitment Materials Dated 5/1/13 

- Schulman Associates IRB (SAIRB) Approval Letter and Supporting Documents 

d. Volume 3: AEATF-II Pour Solid Protocol Submission 

- Records of SAIRB Review of Study AEA07 and Correspondence 

- SAIRB Meeting Minutes 

e. Volume 4: AEATF-II Pour Solid Protocol Submission 

- CVs and Ethics Training Records 

- AEATF II Standard Operating Procedures (SOPs) Referenced in AEA07 Protocol 

f. AEATF II Supplemental Submission of Toxicity Study Summaries for Cyanuric 

Acid (CYA) 

g. Schulman Associates IRB Standard Operating Procedures (dated December 2012) 

h. Schulman Associates IRB Board Members for 2013 

i. Charge Questions 

2. AEATF II Protocol – Brush and Roller Painting: 

Second, the Board will consider a new scenario design and associated protocol from the 

AEATF-II describing proposed research to monitor dermal and inhalation exposure to 

individuals who apply latex paint containing antimicrobial pesticide products with brush and 

roller equipment. Because the proposed research involves scripted exposure, it meets the 

regulatory definition of “research involving intentional exposure of a human subject” and thus is 

covered by subparts K and L of EPA’s amended rule for the protection of human subjects of 

research. The rule at 40 CFR §26.1125 requires a sponsor or investigator to submit to EPA, 

before conducting a study involving intentional exposure of human subjects, the protocol and 

related materials describing the proposed human research. In addition, EPA’s regulation at 40 

CFR §26.1601 requires EPA to perform science and ethics reviews of the submitted proposal and 
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to seek HSRB review of the proposed research. EPA has reviewed the scenario design and 

protocol, and has concluded that the research, with minor revisions, is likely to generate 

scientifically sound, useful information and to meet the applicable provisions of the EPA 

regulations in 40 CFR part 26, subparts K and L. The charge questions and documents being 

transmitted to the HSRB for review are listed below. 

Charge Questions: 

If the AEATF-II study proposal AEA09 is revised as suggested in EPA’s review and if the 

research is performed as described: 

1. Is this research is likely to generate scientifically reliable data, useful for assessing the 

exposure of those who apply latex paint containing an antimicrobial pesticide using a brush 

or roller? 

2. Is the research likely to meet the applicable requirements of 40 CFR part 26, subparts K and 

L? 

Documents: EPA is providing for HSRB review the following 11 documents:

a. EPA Science and Ethics Review of AEATF-II Brush and Roller Painting Scenario 

Design and Protocol for Exposure Monitoring (dated March 14, 2014) 

b. Volume 1: AEATF-II Brush and Roller Protocol Submission 

- AEATF-II’s Transmittal Letter 

- 40 CFR 26.1125 Checklist 

- Study Design Document 

c. Volume 2: AEATF-II Brush and Roller Protocol Submission 

- Draft study protocol dated 1/22/14 

- Draft informed consent form dated 1/22/14 

- Draft recruitment materials dated 1/22/14 

- Schulman Associates IRB (SAIRB) Conditional Approval Letter 

- California Department of Pesticide Regulation (CDPR) review and response 

documentation 

d. Volume 3: AEATF-II Brush and Roller Protocol Submission 

- Records of SAIRB Review of Study AEA09 and Correspondence 

- CDPR Communications 

e. Volume 4: AEATF-II Brush and Roller Protocol Submission 

- AEATF-II SOPs Referenced in AEA09 Protocol 

f. Statistics file: Fold accuracy (LST file) 

g. Statistics file: Fold accuracy (SAS file) 
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h. Statistics file: Power (LST file) 

i. Statistics file: Power accuracy (SAS file) 

j. Schulman Associates IRB Standard Operating Procedures (dated December 2012) 

k. Charge Questions 

3. AEATF II Protocol – Removal Efficiency Study Protocol: 

Third, the Board will consider a new protocol from the AEATF-II describing proposed 

research to measure the removal efficiency of the antimicrobial active ingredient 1,2-

Benzisothiazol-3(2H)-one (BIT) in latex paint and in isopropyl alcohol from human hands. 

Because the proposed research involves scripted exposure, it meets the regulatory definition of 

“research involving intentional exposure of a human subject” and thus is covered by subparts K 

and L of EPA’s amended rule for the protection of human subjects of research. The rule at 40 

CFR §26.1125 requires a sponsor or investigator to submit to EPA, before conducting a study 

involving intentional exposure of human subjects, the protocol and related materials describing 

the proposed human research. In addition, EPA’s regulation at 40 CFR §26.1601 requires EPA 

to perform science and ethics reviews of the submitted proposal and to seek HSRB review of the 

proposed research. EPA has reviewed the scenario design and protocol, and has concluded that 

the research, with minor revisions, is likely to generate scientifically sound, useful information 

and to meet the applicable provisions of the EPA regulations in 40 CFR part 26, subparts K and 

L. The charge questions and documents being transmitted to the HSRB for review are listed 

below. 

Charge Questions: 

If the AEATF-II study proposal AEA08 is revised as suggested in EPA’s review and if the 

research is performed as described: 

1. Is this research likely to generate scientifically reliable data, useful for determining the 

removal efficiency of BIT from the hands due to dermal exposure associated with the use of 

latex paint and non-paint liquid solutions containing containing BIT? 

2. Is the research likely to meet the applicable requirements of 40 CFR part 26, subparts K and 

L? 

Documents: EPA is providing for HSRB review the following 7 documents:

a. EPA Science and Ethics Review of AEATF-II Removal Efficiency Study Protocol 

(dated March 18, 2014) 

b. Volume 1: AEATF-II Removal Efficiency Study Protocol Submission 

- AEATF-II’s Transmittal Letter 

- 40 CFR 26.1125 Checklist 
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c. Volume 2: AEATF-II Removal Efficiency Study Protocol Submission 

- Draft study protocol dated 1/23/14 

- Draft informed consent form dated 1/23/14 

- Draft recruitment materials dated 1/23/14 

- Schulman Associates IRB (SAIRB) Conditional Approval Letter 

- California Department of Pesticide Regulation (CDPR) review and response 

documentation 

d. Volume 3: AEATF-II Removal Efficiency Study Protocol Submission 

- Records of SAIRB Review of Study AEA08 and Correspondence 

- CDPR Communications 

e. Volume 4: AEATF-II Removal Efficiency Study Protocol Submission 

- AEATF-II SOPs Referenced in AEA08 Protocol 

f. Schulman Associates IRB Standard Operating Procedures (dated December 2012) 

g. Charge Questions 

4. USDA Protocol – Evaluation of Bite Protection from Repellent-Treated Clothing for 

the United States Military: 

Fourth, the Board will consider a new protocol from the U.S. Department of Agriculture 

describing proposed research to determine the bite protection level provided by etofenproxtreated U.S. Military Fire Resistant Army Combat Uniforms (FRACUs). Because the proposed 

research involves scripted exposure, it meets the regulatory definition of “research involving 

intentional exposure of a human subject” and thus is covered by subparts K and L of EPA’s 

amended rule for the protection of human subjects of research. The rule at 40 CFR §26.1125 

requires a sponsor or investigator to submit to EPA, before conducting a study involving 

intentional exposure of human subjects, the protocol and related materials describing the 

proposed human research. In addition, EPA’s regulation at 40 CFR §26.1601 requires EPA to 

perform science and ethics reviews of the submitted proposal and to seek HSRB review of the 

proposed research. EPA has reviewed the scenario design and protocol, and has concluded that 

the research, with minor revisions, is likely to generate scientifically sound, useful information 

and to meet the applicable provisions of the EPA regulations in 40 CFR part 26, subparts K and 

L. The charge questions and documents being transmitted to the HSRB for review are listed 

below. 

Charge Questions: 

If the USDA study proposal is revised as suggested in EPA’s review and if the research is 

performed as described: 

1. Is the protocol “Laboratory Evaluation of Bite Protection From Repellent Impregnated 

Clothing for the United States Military” likely to generate scientifically reliable data, useful 
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for estimating the level of mosquito bite protection provided by two different textiles treated 

with etofenprox? 

2. Is the research likely to meet the applicable requirements of 40 CFR part 26, subparts K and 

L? 

Documents: EPA is providing for HSRB review the following 7 documents:

a. EPA Science and Ethics Review of USDA Protocol to Evaluate Bite Protection from 

Repellent-treated clothing for the United States Miliary (dated March 19, 2014) 

b. Volume 1: USDA Protocol Submission 

- Protocol dated 2/28/14 (approved by Western Institutional Review Board (WIRB) 

on 3/4/14) 

- WIRB-approved informed consent form 

- WIRB-approved recruitment materials 

- WIRB Approval Letter 

c. Volume 2: USDA Protocol Submission 

- Records of WIRB Review 

d. Volume 3: USDA Protocol Submission 

- Statistical Methods: Supplemental Information 

e. WIRB SOPs and Policies 

f. WIRB Meeting Minutes 

g. Charge Questions