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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 St udies 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 th e 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 di scussed further below:

1. A proposal for new research to be conduc ted 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 prot ocol from the Agricultural Handler Exposure Task Force (AHETF), describing proposed rese arch 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 Exposur e Assessment Task Force II (AEATF-II) of completed research monitoring the exposure of janitorial workers cleaning floors with an antimicrobial pesticide app lied with a bucket and mop.

Page 1 of 74. An amended scenario design and associated protocol from the Agricultural Handler Exposure Task Force (AHETF), describing propo sed 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 St udy 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 th e repellency to mosquito es 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 §26.11 25 requires a sponsor or investigator to submit to EPA, before conducting a study involving intentiona l 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 rese arch. 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 “researc h involving inten tional exposure of a human subject,” and thus these provisions of regulation apply to it.

EPA has reviewed both the scientific and et hical 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 applic able provisions of the EPA regulations in 40 CFR part 26, subparts K and L.

1. EPA is providing for HSRB Review the fo llowing 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 Revi ew of No Mas-003 (10/1/10)

Charge Questions:

If the proposed field repellenc y 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 reliabl e data, useful for assessing the efficacy of the tested material in repelling mosquitoes?

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

K and L?

Page 2 of 72. 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 re ceived by professionals who mix, load, or apply pesticides using various types of equipment. Both agricultural and antimicrobial pesticide

handler scenarios have been considered. At th is 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 Exposur e 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 i nvolves 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 result ing 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 pestic ide handlers who apply pe sticides in these use

scenarios. Data from this research addressi ng 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 sc ripted exposure, it meets the regulatory definition of “research involving in tentional 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 s ponsor or investigator to s ubmit 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 regul ation at 40 CFR §26.1601 requires EPA to perform science and ethics revi ews 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 fo llowing 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

Page 3 of 7c. Supplement 2: Providing Individual Exposure Information to Subjects

d. Supplement 3: Explanation of AH ETF Spanish translation project

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

Charge Questions :

If the proposed AHETF Right-o f-Way application scenario and field study proposal AHE400 is revised as suggested in EPA’s revi ew and if the research is performed as

described:

a. Is the research likely to generate scientif ically reliable data, us eful 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 appli cable 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 pr ofessional janitorial wo rkers who clean floors with an antimicrobial pesticide product using a mop and bucket. After revisions to address EPA, HSRB, and California DPR commen ts, 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 Ex posure 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 addressi ng exposures from mopping and dumping the spent mop solu tion 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 e xposure, it meets the regulatory definition of “research involving inten tional 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 info rmation, and [to] document its conclusions

Page 4 of 7regarding the scientific and ethical conduct of the researc h.” 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 CF R part 26, subparts A through L.

3. EPA is providing for HSRB review the follo wing materials concerning the completed AEATF II study of the exposure of workers w ho 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 stratu m 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 Statisti cal Analysis (9-28-10) b. AEATF Mop Stats SAS File c. Mopsummary092810 – input to SAS code d. Mop.summary.results.092810 e. Instructions for Repli cating Statistical Analysis

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Additional reference files:

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

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

h. IIRB, Inc., Roster and Procedures

Page 5 of 7i. 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 c onsidered 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 de termination that the study was conducted in substantial compliance with subpa rts 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 inhalati on 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 HS RB in June 2009. The AHETF has since revised them to use different surrogate chemicals. Thos e 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 fo llowing 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 AH ETF Spanish translation project

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

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Page 6 of 7Additional 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 resear ch is performed as described:

a. Is the research likely to generate scientif ically reliable data, us eful for assessing the exposure of handlers who mix and load pe sticides in water-soluble packaging?

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

K and L?

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