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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON D.C., 20460

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

October 4, 2010 

MEMORANDUM

SUBJECT: Materials for review by the Human Studies Review Board for its October 2010 

Meeting

TO: Jim Downing 

 Designated Federal Official 

 Human Studies Review Board 

 Office of Science Advisor (8105R) 

FROM: William L. Jordan 

 Senior Policy Adviser 

 Office of Pesticide Programs (7501P) 

This memorandum describes the materials OPP is providing for review by the Human 

Studies Review Board (HSRB or Board) at the meeting scheduled for October 27-28, 2010. At 

this meeting EPA will ask the Board to address scientific and ethical issues surrounding these 

topics, each of which is discussed further below: 

1. A proposal for new research to be conducted by Carroll-Loye Biological Research to 

evaluate in the field the repellent efficacy to mosquitoes of an unregistered product “No 

Mas” containing 16% Para-menthane-3,8-diol (PMD) and 2% Lemongrass oil. 

2. A new scenario design and associated protocol from the Agricultural Handler Exposure 

Task Force (AHETF), describing proposed research to monitor at 7 sites the exposure of 

experienced workers who apply herbicides for vegetation control in utility rights-of-way 

using backpack or hand-gun sprayers. 

3. A report from the Antimicrobials Exposure Assessment Task Force II (AEATF-II) of 

completed research monitoring the exposure of janitorial workers cleaning floors with an 

antimicrobial pesticide applied with a bucket and mop.

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4. An amended scenario design and associated protocol from the Agricultural Handler 

Exposure Task Force (AHETF), describing proposed research to monitor at 5 sites the 

exposure of experienced workers who mix and load pesticides formulated in watersoluble packaging. 

1. Proposed CLBR Mosquito Repellent Study No Mas-003 with formulation containing 

PMD and Lemongrass Oil.

In earlier meetings the HSRB has reviewed proposals from Carroll-Loye Biological 

Research (CLBR) for several field studies of mosquito repellency of various formulations. This 

new proposal, No Mas-003, is for a field study of the repellency to mosquitoes of a new repellent 

product containing 16% Para-menthane-3,8-diol (PMD) and 2% Lemongrass oil. Apart from the 

new test material, the proposal is generally similar to previous Carroll-Loye field studies 

reviewed by the Board. 

EPA’s regulation at 40 CFR §26.1125 requires a sponsor or investigator to submit to 

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

supporting 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 submitted proposals, 

and to seek HSRB review of the proposed research. Because the proposed research involves 

exposure of subjects that would not occur but for their participation in the research, it meets the 

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

these provisions of regulation apply to it. 

EPA has reviewed both the scientific and ethical aspects of Carroll-Loye protocol No 

Mas-003, and has concluded that, with minor revisions, it 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. 

1. EPA is providing for HSRB Review the following materials on the proposed CarrollLoye mosquito repellent efficacy study No Mas-003: 

a. CLBR Protocol No Mas-003 (7/15/10) 

b. EPA Science and Ethics Review of No Mas-003 (10/1/10) 

Charge Questions:

If the proposed field repellency study protocol No Mas-003 is revised as suggested in 

EPA’s review and if the research is performed as described: 

 

a. Is the research likely to generate scientifically reliable data, useful for assessing the 

efficacy of the tested material in repelling mosquitoes? 

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

K and L? 

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2. Proposed AHETF research on exposure of workers applying pesticides for vegetation 

control in rights of way using backpack or hand gun sprayers.

In several previous meetings the HSRB has considered the design and conduct of 

research to measure the levels of exposure received by professionals who mix, load, or apply 

pesticides using various types of equipment. Both agricultural and antimicrobial pesticide 

handler scenarios have been considered. At this meeting the Board will consider two companion 

proposed handler exposure scenarios involving workers who apply herbicides for vegetation 

control in utility rights of way. This proposal is generally similar to others the Board has seen 

before from the Agricultural Handler Exposure Task Force (AHETF), but differs in some 

important ways. 

This new proposal describes two similar but distinct scenarios, both involving application 

of herbicides in rights of way. One scenario involves application using a backpack sprayer; the 

other involves application using a handgun sprayer. Each scenario calls for collection of samples 

from three workers at each of seven sites, for a total of 21 Monitoring Units (MUs) for each 

scenario, and 42 MUs in all. 

When the scenario is complete, the resulting data will be posted to the Agricultural 

Handler Exposure Database (AHED®). EPA intends to use these data generically to estimate 

daily dermal and inhalation exposures of pesticide handlers who apply pesticides in these use 

scenarios. Data from this research addressing exposure from spraying only can be combined 

with data from an appropriate mixing/loading scenario to estimate exposures of pesticide 

handlers who both mix/load and apply. 

 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 AHETF Rights of Way Application scenario definitions and the 

associated protocol AHE400, and has concluded that they are likely to generate scientifically 

sound, useful information and, with minor revisions, to meet the applicable provisions of the 

EPA regulations in 40 CFR part 26, subparts K and L. 

2. EPA is providing for HSRB review the following materials concerning the AHETF 

proposal for monitoring applicators using backpack or handgun sprayers to apply 

herbicides in utility rights of way: 

a. Final Submission for Review of AHE400 (6-18-10) 

b. Supplement 1: SOPs cited in AHE400 

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c. Supplement 2: Providing Individual Exposure Information to Subjects 

d. Supplement 3: Explanation of AHETF Spanish translation project 

e. EPA Science & Ethics Review AHE400 ROW Final (9-30-10) 

Charge Questions: 

If the proposed AHETF Right-of-Way application scenario and field study proposal 

AHE400 is revised as suggested in EPA’s review and if the research is performed as 

described: 

a. Is the research likely to generate scientifically reliable data, useful for assessing the 

exposure of workers who apply pesticides in utility rights of way using backpack or 

handgun sprayers? 

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

K and L? 

3. Completed AEATF II research on exposure of workers applying antimicrobial 

pesticides to floors using mop and bucket.

In its meeting in April 2008 the HSRB reviewed favorably a proposal from the 

Antimicrobial Exposure Assessment Task Force II (AEATF II) for research to measure the levels 

of dermal and inhalation exposure received by professional janitorial workers who clean floors 

with an antimicrobial pesticide product using a mop and bucket. After revisions to address EPA, 

HSRB, and California DPR comments, this research was conducted in the summer of 2009 and 

reported and submitted to EPA in the summer of 2010. 

At this meeting the Board will review the reports of this completed work, the first 

scenario to be completed by the AEATF II. 

If the data for the Mop Scenario are accepted by EPA, the resulting data will be posted to 

the Biocide Handlers Exposure Database (BHED®). EPA intends to use these data generically to 

estimate daily dermal and inhalation exposures of those who clean floors with antimicrobial 

pesticides using a mop and pail. Data from this scenario addressing exposures from mopping 

and dumping the spent mop solution can be combined with data from an appropriate 

mixing/loading scenario to estimate exposures of workers who both mix/load and apply. 

Because this research involved scripted exposure, it meets the regulatory definition of 

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

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

CFR §26.1303 requires the submitter of reports of completed human research to document its 

ethical conduct. The rule at 40 CFR §26.1602(a) requires EPA to “review the material submitted 

under §26.1303 and other available, relevant information, and [to] document its conclusions 

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regarding the scientific and ethical conduct of the research.” The rule at 40 CFR §26.1602(b) 

further requires EPA to submit the data and EPA’s review to the HSRB if it decides to rely on 

the data. 

EPA has reviewed the AEATF II Mop Scenario report and supplements and has 

concluded that it provides scientifically sound, useful information, and was conducted in 

substantial compliance with 40 CFR part 26, subparts A through L. 

3. EPA is providing for HSRB review the following materials concerning the completed 

AEATF II study of the exposure of workers who use antimicrobial pesticides to clean 

floors using a mop and pail. 

a. MRID 48210201 Mop Study Final Report (7-28-10) 

Note that Appendices Q and R, pp. 583-2116, are superseded by pp. 163-1146 in 

Supplement 1 

b. MRID 48231201 Supplement 1 to Mop Study Final Report 

Includes protocol with tracked changes, more detailed chronology, and more 

complete, indexed versions of Appendices Q and R. 

c. MRID 48231901 Supplement 2 to Mop Study Final Report 

Explains rationale for leaving ME stratum definitions unchanged in spite of HSRB 

comments 

d. EPA Ethics Review of AEATF Mop Study (10-4-10) 

e. EPA Science Review of AEATF Mop Study (10-4-10) 

Statistics Supplement to EPA Science Review: 

a. J. Cohen Statistical Analysis (9-28-10) 

b. AEATF Mop Stats SAS File 

c. Mopsummary092810 – input to SAS code 

d. Mop.summary.results.092810 

e. Instructions for Replicating Statistical Analysis 

 ******************************************************************** 

 Additional reference files: 

f. EPA Science & Ethics Review of Mop Study Proposal (3-10-08) 

g. HSRB Comments on Mop Study Proposal (6-25-08) 

h. IIRB, Inc., Roster and Procedures 

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i. AEATF II SOPs 

Charge Questions: 

a. Was the research reported in the Antimicrobial Exposure Assessment Task Force II 

(AEATF–II) completed study report AEA03 and associated supplemental reports 

faithful to the design and objectives of the protocol and governing documents of 

AEATF-II? 

b. Has the Agency adequately characterized, from a scientific perspective, the 

limitations on these data that should be considered when using the data in estimating 

exposure of those who apply antimicrobial floor-cleaning products with mop and 

bucket? 

c. Does available information support a determination that the study was conducted in 

substantial compliance with subparts K and L of 40 CFR Part 26? 

4. Revised proposal for AHETF research on exposure of workers mixing/loading 

pesticides in water-soluble packaging. 

The Agricultural Handler Exposure Task Force (AHETF) has submitted a revised 

proposal for research on dermal and inhalation exposures of workers who mix and load 

pesticides formulated in water-soluble packaging. The original design and protocol for this 

scenario were reviewed favorably by the HSRB in June 2009. The AHETF has since revised 

them to use different surrogate chemicals. Those changes forced other revisions in turn; taken 

together, the proposed changes are significant enough to warrant a new review of the revised 

proposal by the HSRB. 

4. EPA is providing for HSRB review the following materials concerning the revised 

AHETF proposal for monitoring workers who mix and load pesticides in water-soluble 

packaging: 

a. AHE120 Mix-Load WSP Revised Scenario (8-19-10) 

b. Supplement 1: SOPs cited in AHE120 

c. Supplement 2: Providing Individual Exposure Information to Subjects 

d. Supplement 3: Explanation of AHETF Spanish translation project 

e. EPA Science & Ethics Review of Rvsd AHE120 M-L WSP (10-1-10) 

*************************************************************** 

 

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Additional reference Files: 

f. EPA Science & Ethics Rvw of Original AHE120 Proposal (4-8-09) 

g. HSRB Comments on Original AHE120 Proposal (10-26-09) 

Charge Questions: 

If the revised AHETF scenario and field study proposal AHE120 is revised as suggested 

in EPA’s review and if the research is performed as described: 

a. Is the research likely to generate scientifically reliable data, useful for assessing the 

exposure of handlers who mix and load pesticides in water-soluble packaging? 

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

K and L? 

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