EPA Human Studies Review Board (HSRB)
January 23-24,2018 Meeting Minutes

Committee Members: (See EPA HSRB Members List - Attachment A)

Date and Time: Tuesday, Jars. 13,1018 and Wednesday, Jan. 14,1018, both 1:00 to 5:30 pm EST.
Locations: Via teleconference and webinar

Purpose: The HSRB provides advice, information and recommendations on issues related to scientific
and ethical aspects of human subjects research.

January 23rd meeting:

Meeting was called to order at 1:00 p.m.by Tom O'Farrell, designated federal official (DFO) for the HSRB.
Roll was taken and the following members and observers were present:

HSRB members

EPA staff members

Liza Dawson, Ph.D. (HSRB Chair)

Michelle Arling (EPA)

Edward Gbur, Jr., Ph.D. (HSRB Vice-Chair)

Timothy Dole (EPA)

Jennifer Cavallari, Sc.D., CIH

Timothy Leighton (EPA)

Alesia Ferguson, Ph.D.

Tim Ciarlo (EPA, OPP)

Kyle L. Galbraith, Ph.D.

Tom Sinks (EPA, OSA)

Walter T. Klimecki, D.V.M., Ph.D.

Eric Bohnenblust (EPA, OPP)

Randy Maddalena, Ph.D.



Jun Zhu, Ph.D.



Members of the public, representatives of



research sponsor and research team



Ulrich Bernier (USDA)



Lisa Setliff (Landis International)



Dan Hollas (S.C. Johnson & Son)



Kevin Sweeney (Landis International)



Dave Barnekow (AHETF, Dow AgroSciences)



AJ Allen (Eli Lilly)



Richard Collier (Landis International)



Tiffany Stecker (Bloomberg)



Ron Lack (public)



Kevin Dunn (Endyna, meeting support contractor)



Tom O'Farrell provided an introduction to the meeting and outlined the Federal Advisory Committee Act
(FACA) procedures. Dr. Tom Sinks of the EPA Office of the Science Advisor welcomed the Board. Ms.
Michelle Arling provided updates regarding respirator use in a study previously reviewed by the HSRB.

The Board reviewed one protocol during the session on January 23'd, "Laboratory Evaluation of Bite
Protection from Repellent-Impregnated Fabrics." The Agency's scientific review of this protocol was

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presented by Mr. Tim Ciarlo of the EPA Office of Pesticide Programs (OPP). Mr. Ciarlo highlighted key
features of the study, which is similar to studies of repellent-treated fabric that the HSRB has previously
reviewed. The study is testing commercially available fabrics treated with 0.52% permethrin or 0.9%
etofenprox and tests repellency of the fabric after 0, 20, 50, and 75 washes. The testing is an arm-in-
cage design in which human subjects wear treated and untreated fabric sleeves over an exposed
forearm that is inserted into a cage. Laboratory reared, disease-free mosquitoes are released into the
cage for a 15-minute period and allowed to land and bite. The subjects' hands are covered with gloves
such that only the sleeve is accessible to mosquitoes for blood feeding. After the test period the
mosquitoes are captured and crushed to determine blood feeding and percentage protection is
calculated.

The study tests two mosquito species: Aedes aegypti and Anopheles albimonus. The study will enroll 10
subjects, and each human subject serves as their own control by testing the untreated fabrics as well as
the range of treated and washed fabric sleeves. Mr. Ciarlo described power calculations showing
adequate statistical power for the study using the 10 subjects with repeated measures testing the 5 sets
of sleeves (control untreated sleeves and four different washing conditions). He also described dermal
toxicity calculations demonstrating that the concentrations of permethrin and etofenprox lead to
Margins of Exposure (MOEs) which are well above the agency's level of concern for these two products;
hence there is no concern about dermal exposure in this study.

Ms. Arling of EPA OPP reviewed ethical aspects of the study protocol. Risks to subjects are appropriately
minimized by using disease-free mosquitoes, excluding individuals with skin conditions, reactivity to
pesticide-treated fabrics, or severe reactivity to mosquito bites; and providing a confidential mechanism
for conducting pregnancy testing for female potential participants. Plans for recruitment and informed
consent were deemed to be appropriate and the study was reviewed by an accredited 1RB, the Western
Institutional Review Board (WIRB). EPA staff recommended minor changes to the protocol related to
timing of procedures and additions to the consent form. The study sponsor and research team agreed
to the requested changes from EPA.

The Scientific review was presented by HSRB board members Randy Maddalena and Walt Klimecki, and
statistical review by board member Ed Gbur. Dr. Klimecki remarked that MOE calculations for
permethrin and etofenprox needed to be harmonized, as the calculations in the protocol did not match
the calculations presented by EPA staff in their review. Dr. Maddalena commented that it was unclear
whether there were issues related to repeated measurements of repellency on a single subject, since
there was no information provided about whether mosquitoes might be more or less attracted to a
subject with previous bites, compared to a subject without bites. Dr. Gbur addressed the statistical
analysis, also commenting on repeated measures and recommending that some analysis of correlation
structure of the repeated measures be undertaken.

There was discussion of these issues by the full board. The Board agreed that the protocol was
scientifically sound and responded affirmatively to the science charge questions. The Board also
recommended some clarifications and corrections in the protocol to address comments by Drs. Klimecki
and Gbur.

HSRB board chair Liza Dawson presented the ethics review of the study. Dr. Dawson stated that there
were no major ethical concerns with the study, but recommended some minor changes for clarity,
addressing inclusion/exclusion criteria, compensation for injury, care and treatment for injury,

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recruitment materials, and informed consent. The Board discussed these changes and responded
affirmatively to the charge question, stating the protocol would be likely to meet the requirements of 40
CFR 26 Subparts K and L if minor changes were made. This concluded the Board's session for January
23rd and the meeting was adjourned.

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January 24th meeting

Meeting was called to order at 1:00 p.m.by Tom O'Farrell, DFO for the HSRB. Roll was taken and the
following members and observers were present:

HSRB members

EPA staff members

Liza Dawson, Ph.D. (HSRB Chair)

Michelle Arling (EPA)

Edward Gbur, Jr., Ph.D. (HSRB Vice-Chair)

Timothy Dole (EPA)

Jennifer Cavallari, Sc.D., CIH

Timothy Leighton (EPA)

Alesia Ferguson, Ph.D.

Matt Crowley (EPA, OPP)

Kyle L. Galbraith, Ph.D.

Jeff Dawson (EPA, OPP)

Walter T. Klimecki, D.V.M., Ph.D.

David Miller (EPA, OPP)

Randy Maddalena, Ph.D.

Dave Jones (EPA, OPP)

Jun Zhu, Ph.D.

Maria Spassova (EPA, NCEA)



Christine Cai (EPA, NCEA)

Members of the public, representatives of the



Agricultural Handlers Exposure Task Force



(AHETF) and research team



Dave Barnekow (AHETF, Dow AgroSciences)



Kevin Dunn (Endyna, meeting support contractor)



Eric Bruce (AHETF)



Dave Johnson (Johnson Management &



Consulting)



Jeff Holmsen (BASF Corp.)



Leah Rosenheck (LR Risk Consulting, Inc.)



Larry Holden (AHETF, Sielken & Associates



Consulting, Inc.)



Steve McEuen (public)



William Jordan (independent consultant)



The HSRB reviewed the Agricultural Handler Exposure Task Force, LLC (AHETF) Study Report AHE170:
"Determination of Dermal and Inhalation Exposure to Workers During Open Pour Loading of Granules."
Mr. Matt Crowley provided EPA's scientific assessment of the study. The study assessed dermal and
inhalation exposure of workers pouring five different granular pesticides products: 2,4-D, chlorpyrifos,
permethrin, pendimethalin and tefluthrin. The monitoring methods were similar to other scenarios
used in previous AHETF studies. Hand exposures were assessed with a handwash method, using
multiple samples taken throughout the day and analyzed separately. Head exposure was assessed with
wipes, which were combined and analyzed as one sample. Other dermal exposure was monitored using
a whole-body dosimeter worn under the clothes and which was analyzed in two separate sections.
Inhalation exposure was assessed using an OSHA versatile sampler worn by the worker, which includes a
small motorized pump for air flow to assess inhalation exposure of each individual worker.

The study design consisted of seven sites monitoring three workers per site. Several amendments were
made to the protocol during the study, mostly with the aim of increasing recruitment and finishing the
study on schedule. None of the amendments were deemed to adversely affect the scientific integrity of
the study. There were also some protocol deviations, most of which related to missing samples. Again,
the deviations were not considered by EPA to affect the soundness of the study or the ability to draw

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conclusions from the results. The study had a good geographic range and distribution of different
products and a wide range of amount of product handled. Positive and negative controls were
appropriate.

With regard to missing hand wash samples, EPA assessed different methods of imputing missing data.
The final method chosen was to simply impute the missing values based on the average across all hand
wash samples. Other methods of imputation did not significantly affect the conclusions of the study.

EPA reviewed the study's ability to meet the two main benchmarks, namely 3-fold accuracy in the
dermal exposure measurements, and statistical power to assess proportionality between exposure and
amount of active ingredient handled (AaiH). Three-fold accuracy, also called a K-factor, refers to the
95% confidence interval around the mean exposure falling within a factor of three relative to the mean.
In this case the three-fold accuracy benchmark was met. With regard to the proportionality question,
the study had greater than 80% power to detect proportionality.

EPA staff described proposed uses of the data as part of risk assessments for worker exposure to new
pesticide products in the agricultural sector, or for re-registration of currently approved products. In
sum, EPA concluded the study was scientifically sound and provided reliable data for decision-making.

Ms. Michelle Arling provided the EPA ethics review of the study. The study was reviewed and approved
by the Schulman IRB, an accredited independent IRB. Ms. Arling described recruitment for the study,
which involved several steps: constructing a list of growers using granular pesticide products; contacting
these employers and inviting them to participate; then visiting the participating growers and meeting
with them to describe the study. Potentially eligible employees were recruited and informed consent
discussions were held. Inclusion criteria specified that workers must be experienced handling granular
pesticides, be non-pregnant adults, and be over the age of 18. Consent materials were prepared in both
English and Spanish; however, none of the participants requested Spanish language consent discussions
or materials. During the study, all workers wore personal protective equipment (PPE) specified by the
product label of the products they were loading. Heat stress was monitored throughout the study. A
nurse was available in case of any medical issues during the conduct of the study, but no medical issues
requiring nurse assistance were identified. There were several amendments to the protocol, all of which
were reviewed and approved by the IRB prior to implementation. In short, there were no ethical
concerns with the study conduct or ethical review procedures. EPA concluded that the study satisfied
the criteria of 40 CFR 26 parts K and L.

The HSRB presented their scientific and statistical review of the study. Dr. Alesia Ferguson raised a
question about missing samples and asked for clarifications about how the data were handled from
missing samples. Dr. Cavallari also requested clarification on the method of data imputation for missing
samples. Both Dr. Cavallari and Dr. Ferguson commented that the study was sound and well conducted
and that they had no major concerns. Dr. Jun Zhu reviewed the statistical aspects of the study and
commented that the mixed effects model used for statistical analysis was appropriate. The HSRB
concluded that the study raised no major scientific concerns and responded affirmatively to the charge
question that the study was scientifically sound, producing reliable results.

The HSRB ethics review was presented by Dr. Kyle Galbraith. Dr. Galbraith commented that the IRB
review of the initial protocol and amendments was handled appropriately, that inclusion and exclusion
criteria were reasonable. Recruitment and informed consent were done appropriately and risks to
subjects were minimized. Dr. Galbraith noted that one issue with the study was the fact that only men

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were enrolled, but because the agricultural workers are overwhelmingly male, it would not have been
feasible or realistic to expect female participants. Dr. Galbraith stated that there was no criticism of the
study about the lack of enrollment of female subjects. In short, the study met the criteria of 40 CFR 26
parts K and L. The HSRB agreed with this assessment and responded affirmatively to the charge
question. This concluded the review of the study, and the meeting was adjourned.

Respectfully submitted:

Thomas O'Farrell

Designated Federal Officer

Human Studies Review Board

United States Environmental Protection Agency

Certified to be true by:

Liza Dawson, Ph.D.

Chair

Human Studies Review Board

United States Environmental Protection Agency

NOTE AND DISCLAIMER: The minutes of this public meeting reflect diverse ideas and
suggestions offered by Board members during the course of deliberations within the meeting.
Such ideas, suggestions and deliberations do not necessarily reflect definitive consensus advice
from the Board members. The reader is cautioned to not rely on the minutes to represent final,
approved, consensus advice and recommendations offered to the Agency. Such advice and
recommendations may be found in the final report prepared and transmitted to the EPA Science
Advisor following the public meeting.

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Attachment A

EPA HUMAN STUDIES REVIEW BOARD MEMBERS

Chair

Liza Dawson, Ph.D.

Research Ethics Team Leader
Division of AIDS

National Institute of Allergy and Infectious Diseases
National Institutes of Health
Bethesda, MD

Vice Chair

Edward Gbur, Jr., Ph.D.

Professor of Statistics

Director, Agricultural Statistics Laboratory

University of Arkansas

Fayetteville, AR

Members

Jennifer Cavallari, Sc.D., CIH
Assistant Professor

Division of Occupational and Environmental

Medicine
University of Connecticut
Storrs, CT

Alesia Ferguson, Ph.D.

Associate Professor
Department of Environmental and

Occupational Health
University of Arkansas
Little Rock, AR

Kyle L. Galbraith. Ph.D.

Human Subjects Protection
Carle Foundation Hospital
Urbana, IL

Walter T. Klirnecki, D.V.M., Ph.D.
Associate Professor
Departments of Pharmacology and
Toxicology

The University of Arizona Health Sciences
Tucson. AZ

Randy Maddalena, Ph.D.

Physical Research Scientist
Indoor Environment Group
Lawrence Berkeley National Laboratory
Berkeley, CA

Jun Zhu, Ph.D.

Professor of Statistics and of Entomology
Department of Statistics
University of Wisconsin-Madison
Madison, WI

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Consultants to the Board

Kendra L. Lawrence, Ph.D., BCE, PMP
Health Sciences Product Manager
U.S. Army Medical Materiel Development Activity
Fort Detrick, MD

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Attachment B

FEDERAL REGISTER NOTICE ANNOUNCING MEETING
ENVIRONMENTAL PROTECTION AGENCY

[FRL-9972-41 -ORD]

Human Studies Review Board; Notification of Public Meetings
AGENCY: Environmental Protection Agency.

ACTION: Notice.

SUMMARY: The Environmental Protection Agency (EPA), Office of the Science Advisor
announces two separate public meetings of the Human Studies Review Board (HSRB) to advise
the Agency on the ethical and scientific review of research involving human subjects.

DATES: A virtual public meeting will be held on Tuesday, January 23, 2018 and Wednesday,
January 24, 2018, from 1:00 pm to approximately 5:30 pm Eastern Time on both dates. A
separate, subsequent teleconference meeting is planned for Thursday, March 15, 2018, from 2:00
pm to approximately 3:30 pm Eastern Time for the HSRB to finalize its Final Report of the
January 23 and 24, 2018 meeting and review other possible topics.

ADDRESSES: Both of these meetings will be conducted entirely by telephone and on the
Internet using Adobe Connect. For detailed access information visit the HSRB Website:
imp: \\\\w 2.i-p;i.Lun .'u^a Iniman-sUidii'S-ivYiow'-hoard

FOR FURTHER INFORMATION, CONTACT: Any member of the public who wishes to
receive further information should contact the HSRB Designated Federal Official (DFO),
Thomas O'Farrell on telephone number (202) 564-8451; fax number: (202) 564-2070; email
address: ofarrell.thomas@epa.gov; or mailing address: Environmental Protection Agency, Office

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of the Science Advisor, Mail code 8105R, 1200 Pennsylvania Avenue NW, Washington, DC
20460.

SUPPLEMENTARY INFORMATION:

Meeting access: These meetings will be open to the public. The full Agenda and meeting
materials will be available at the HSRB Website: hup: \\ w\\ Z.cpa.gm osn human-studics-
rcvicw-board . For questions on document availability, or if you do not have access to the
Internet, consult with the DFO, Thomas O'Farrell, listed under FOR FURTHER
INFORMATION, CONTACT.

Special accommodations. For information on access or services for individuals with disabilities,
or to request accommodation of a disability, please contact the DFO listed under FOR
FURTHER INFORMATION, CONTACT at least 10 days prior to the meeting to give EPA as
much time as possible to process your request.

How May I Participate in this Meeting?

The HSRB encourages the public's input. You may participate in these meetings by following
the instructions in this section.

1. Oral comments. To pre-register to make oral comments, please contact the DFO,
Thomas O'Farrell, listed under FOR FURTHER INFORMATION, CONTACT Requests to
present oral comments during either meeting will be accepted up to Noon Eastern Time on
Tuesday, January 16, 2018, for the January 23 and 24, 2018 meeting and up to Noon Eastern
Time on Tuesday, March 8, 2018 for the March 15, 2018 meeting. To the extent that time
permits, interested persons who have not pre-registered may be permitted by the HSRB Chair to
present oral comments during either meeting at the designated time on the agenda. Oral

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comments before the HSRB are generally limited to five minutes per individual or organization.
If additional time is available, further public comments may be possible.

2. Written comments. Submit your written comments prior to the meetings. For the
Board to have the best opportunity to review and consider your comments as it deliberates, you
should submit your comments by Noon Eastern Time on Tuesdav, January 16,2018, for the
January 23 and 24,2018 meeting and up to Noon Eastern Time on Tuesday, March 8,2018 for
the March 15,2018 meeting. If you submit comments after these dates, those comments wi 11 be
provided to the HSRB members, but you should recognize that the HSRB members may not
have adequate time to consider your comments prior to their discussion. You should submit your
comments to the DFO, Thomas O'Farrell listed under FOR FURTHER INFORMATION,
CONTACT. There is no limit on the length of written comments for consideration by the HSRB.
Background

The HSRB is a Federal advisory committee operating in accordance with the Federal Advisory
Committee Act 5 U.S.C. App.2 § 9. The HSRB provides advice, information, and
recommendations on issues related to scientific and ethical aspects of third-party human subjects
research that are submitted to the Office of Pesticide Programs (OPP) to be used for regulatory
purposes.

Topic for discussion. On January 23 and 24, 2018, EPA's Human Studies Review Board will
consider two topics: 1) A completed study and monograph report titled "Agricultural Handler
Exposure during Open Pour Loading of Granules" by the Agricultural Handlers Exposure Task
Force, and 2) a study protocol titled "Laboratory Evaluation of Bite Protection From Repellent-
Impregnated Fabrics" by Pinebelt Industries.

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The Agenda and meeting materials for this topic will be available in advance of the meeting at
liltp: "w,\\osa human-sHidies-rcvicw-hoard.

On March 15,20183 the HSRB will review and finalize their draft Final Report from the January
23 and 24, 2018 meeting, in addition to other topics that may come before the Board. The HSRB
may also discuss planning for future HSRB meetings. The agenda and the draft report will be
available prior to the meeting at http:/7'w\\ w2.epa.uov/osa/huirK>n-siudk's-rcvii'\v-hoard.

Meeting minutes and final reports. Minutes of these meetings, summarizing the matters
discussed and recommendations made by the HSRB, will be released wilhin 90 calendar days of
the meeting. These minutes will be available at http:' w ww2.cpa.'jov 'osa human-studies-review-
board. In addition, information regarding the HSRB's Final Report, will be found at
httpi' \\\u\2.cp;i.go\ osadniman-studies-rcx jew -hoard or from Thomas OTarrell listed under
FOR FURTHER INFORMATION, CONTACT.

Date:				JenniferQrmc-Zavaleta. Ph.D.

EPA Science Advisor

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