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Minutes of the

United States Environmental Protection Agency (EPA) 

Human Studies Review Board (HSRB)

January 17, 2013 Public Meeting

Docket Number: EPA-HQ-ORD-2012-0892

HSRB Website: http://www.epa.gov/osa/hsrb

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

Date and Time: Thursday, January 17, 2013, 1:00 – 5:00 PM

(See Federal Register Notice—Attachment B) 

Location: EPA, One Potomac Yard (South Building), 2777 S. Crystal Drive, 

Arlington, VA 22202

Purpose: The EPA HSRB provides advice, information and recommendations 

on issues related to the scientific and ethical aspects of human 

subjects research. 

Attendees: Chair: Rebecca T. Parkin, Ph.D., M.P.H.

Vice Chair: Jewell H. Halanych, M.D.

Board Members: George C.J. Fernandez, Ph.D.

Sidney Green, Jr., Ph.D., Fellow, ATS

Elizabeth Heitman, Ph.D.

Dallas E. Johnson, Ph.D.

John C. Kissel, Ph.D.

José E. Manautou, Ph.D.

William J. Popendorf, Ph.D.

^Nu-May Ruby Reed, Ph.D., D.A.B.T.

Leonard Ritter, Ph.D., ATS

Virginia Ashby Sharpe, Ph.D.

Linda J. Young, Ph.D.

Meeting Summary: Meeting discussions generally followed the issues and general timing as 

presented in the meeting Agenda (Attachment C), unless noted otherwise. 

Commencement of Public Meeting and Review of Administrative Procedures

Mr. Jim Downing (Designated Federal Officer [DFO], HSRB [or Board], Office of the 

Science Advisor [OSA], EPA [or Agency]) convened the meeting at 1:00 p.m. and welcomed

Board members, EPA colleagues and members of the public. He thanked the Board members for

their work in preparing for the meeting deliberations.

Mr. Downing noted that in his role as the DFO under the Federal Advisory Committee 

Act (FACA), he serves as liaison between the HSRB and EPA and is responsible for ensuring that 
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all FACA requirements are met. The DFO must work with appropriate Agency officials to ensure 

that all appropriate ethics regulations are satisfied regarding conflicts of interest; HSRB members 

have been briefed on federal conflict of interest laws and have completed a standard government 

financial disclosure report. In consultation with the deputy ethics officer for OSA and the Office 

of the General Counsel, Mr. Downing has reviewed the reports to ensure that all ethics 

requirements are met.

Mr. Downing informed members that there is an interesting and significant topic on the

agenda for the meeting. He noted that agenda times are approximate, and the group will be kept 

to those times as closely as possible. All speakers, including Board members and members of 

the public, should use their microphone and identify themselves before speaking, as the 

meeting is being recorded and broadcast on the Internet. During Board discussions, if members 

require clarification from the public, they may request such information through the Chair or 

DFO. Copies of the meeting materials, supporting documents and public comments will be

available at http://www.regulations.gov under docket number EPA-HQ-ORD-2012-0892 and

most are available on the HSRB website at http://www.epa.gov/osa/hsrb. Following the

presentations, time has been scheduled for questions of clarification to EPA staff and the

principal investigator and sponsors of the studies. This time is to be used for points of

clarification rather than Board discussion. A public comment period will be maintained, and

remarks must be limited to 5 minutes. No members of the public had pre-registered to make a 

public comment for the topic under consideration. Meeting minutes, including a description of

the matters discussed and conclusions reached by the Board, will be prepared and must be

certified by the meeting Chair within 90 days. The HSRB also will prepare a final report in

response to questions posed by the Agency that will include the Board’s review and analysis of

materials presented. EPA will announce in the Federal Register a public conference call meeting 

for the Board’s review and subsequent approval of the Final Report. Mr. Downing turned the

meeting over to the HSRB Chair, Dr. Rebecca Parkin. 

Introduction and Identification of Board Members

Dr. Parkin welcomed the Board members and said a new member, Dr. Nu-May Ruby

Reed, would be monitoring the meeting via teleconference. She asked Board members to

introduce themselves, and members completed their introductions. Dr. Parkin next referred to 

Mr. Downing, who invited Dr. Glenn Paulson (Science Advisor, EPA) to offer welcoming

remarks.

Welcoming Remarks

Dr. Paulson welcomed all in attendance to the first HSRB meeting of 2013. One of the 

responsibilities of the Science Advisor is to provide administrative oversight of the workings of 

the HSRB, which is a FACA committee. For the first time since the HSRB was created, the EPA 

Science Advisor has only one set of duties, albeit wide ranging. Prior to his appointment, the 

Science Advisor and the Assistant Administrator for the Office of Research and Development 

(ORD) was the same person. The duties of these positions now are divided equally between two 

people. Dr. Paulson indicated that he would be happy to answer any questions about his broader 

responsibilities. He joined Mr. Downing and Dr. Parkin in expressing appreciation to the Board 

members for their service in preparing, participating and following up for this meeting. As a 
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former member of many federal committees, he recognized and appreciated both the time 

required and the amount of material reviewed to prepare for the deliberations during the meeting. 

He also appreciated the Board’s commitment to these issues in view of other obligations. Dr.

Paulson welcomed members of the public and thanked the Office of Pesticide Programs (OPP), 

OSA and other EPA colleagues for the work leading up to this formal public meeting. 

Dr. Paulson next noted changes to the Board. He welcomed Dr. Parkin, who has been a 

Board member since October 2007 and previously served as interim Vice Chair, in her new role 

as Chair through August 2013. He remarked that the EPA team looks forward to working with 

her in her capacity as Board Chair to advise EPA on scientific and technical issues regarding 

third-party research on human subjects. In addition, Dr. Jewell Halanych will serve as the 

Board’s Vice Chair through August 2014. Dr. Paulson also welcomed three new members,

noting EPA’s appreciation at their acceptance to serve on the HSRB and anticipation to access 

their expertise in reviewing ethical and scientific issues. The three new members were introduced 

as follows:

 Dr. Elizabeth Heitman, Vanderbilt University, has faculty appointments in the 

Department of Medicine’s Division of General Medicine and Division of Critical Care, as 

well as in the Department of Religious Studies. Her work focuses on the cultural and

religious aspects of medicine, biomedical science and public health, particularly 

regarding education and community experience. Her primary research addresses the 

evaluation of education and research ethics, responsible conduct of research, and cultural 

awareness of professional socialization of students and researchers. She serves as the CoChair of the Ethics Committee and a member of the Critical Care Committee and the 

Organ Donation Advisory Committee at the Vanderbilt University Medical Center.

 Dr. John Kissel is a Professor of Environmental and Occupational Health Sciences at the 

University of Washington. He holds a Ph.D. in civil and environmental engineering and is 

a registered Professional Engineer. His research involves human exposure assessment 

related to waste management practices, including agricultural and residential use of 

pesticides and consumer products. His current interest relates to probabilistic predictions 

of human exposure and the reconciliation of predictions with biomarker data.

 Dr. Nu-May Ruby Reed is a recently retired toxicologist from the California EPA 

(Cal/EPA) Department of Pesticide Regulation, where she served as the lead scientist in 

risk assessment issues. Her research interests include evaluating health risks and 

developing pesticide risk assessments. She also has represented her Department regarding 

community concerns and emergency response. 

Dr. Paulson informed members that on December 19, 2012, he met with a group of 

experts in human subjects protection, co-chaired by Dr. Mary Swigar, Robert Wood Johnson 

Medical School, University of Medicine and Dentistry of New Jersey, to review and evaluate 

EPA’s Human Subjects Research Program and provide recommendations to EPA to strengthen 

the Agency’s program for the protection of human research subjects in future years. The 

retirement of Dr. Warren Lux, the Human Subjects Research Review Official (HSRRO), seemed 

an appropriate time to review and reevaluate EPA’s program for human subject protections. This 

group of experts will meet again in March 2013 to provide their recommendations.
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EPA will announce the position of HSRRO later in January 2013. A search committee 

has been established and will evaluate applications for this critical position. Dr. Paulson noted 

that Board members already had received this announcement and were asked to disseminate this 

information to procure a strong list of potential candidates for the position.

Dr. Paulson next reviewed the main topic for consideration at this meeting, which is the 

completed study from the Antimicrobial Exposure Assessment Task Force II (AEATF) in which 

the dermal and inhalation exposure of professional janitorial workers was monitored as they

poured liquid antimicrobial pesticide products from conventional or reduced-splash containers 

into different sizes and types of source containers. EPA seeks the HSRB’s advice regarding: 

(1) the scientific soundness of this completed research and on its appropriateness for use in 

estimating exposure that results from pouring liquid antimicrobial pesticide products; and 

(2) whether available information supports a determination that the study was conducted in 

substantial compliance with subparts K and L of 40 Code of Federal Regulations (CFR) part 26. 

He reminded the Board that it had considered the protocol for this study at its October 2011 

meeting and now has the opportunity to review the completed study and provide expert advice 

and recommendations to EPA.

Dr. Parkin thanked Dr. Paulson for his comments, which offer a new context for 

Dr. Paulson’s responsibilities, and said that she and the Board looked forward to working with 

him.

Opening Remarks

Dr. Steven Bradbury, Director, OPP, Office of Chemical Safety and Pollution Prevention

(OCSPP), EPA, welcomed attendees to the meeting and expressed his appreciation for the 

Board’s efforts to help EPA move forward. From EPA’s perspective, the advice and input 

received from the Board has demonstrated that high-quality research can be performed that 

adheres to high standards and ethical conduct. The input from the Board is instrumental in 

facilitating the path forward. The improved quality of protocols and research plans submitted to 

the HSRB over the years is a reflection of the Board’s efforts and input. Investigators have 

learned how to better document protocols and explain their approach, ensuring high-quality

science, ethics and standards. 

The HSRB’s advice has helped EPA undertake internal reviews. It is clear that the 

concepts and insights are penetrating throughout the Agency, such as when staff scientists seek 

advice. Another important aspect is the concept of public participation and transparency, as input 

and comments from the public are critical. EPA makes special efforts to listen to the public so 

that everyone has confidence that the activities undertaken will ensure high-quality science and 

the highest ethical standards. 

Dr. Bradbury also welcomed the new Board members to this effort and thanked 

Drs. Parkin and Halanych for assuming their HSRB leadership roles. He echoed Dr. Paulson’s 

appreciation for the amount of work required for these meetings, including efforts by

Mr. Downing and OSA staff in preparing for the meeting. EPA also appreciates the work in 

preparing the Board’s report and for all input received from the Board, EPA colleagues and the 

public. 
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Dr. Parkin added her gratitude to the EPA staff. She noted that this meeting and agenda 

item had been delayed because Hurricane Sandy in November 2012 had prevented a quorum of 

Board members from attending, and she encouraged all to remember the people who still are 

affected deeply by that storm.

OPP Follow-Up on Previous HSRB Recommendations

Dr. Parkin welcomed Mr. William Jordan (OPP, EPA) to present the follow-up of the 

Board’s previous recommendations. Mr. Jordan provided a brief overview of the context that led 

to the Board’s review of the AEATF study report to communicate how the information that 

resulted from the study will be used. He indicated that he would first provide an overview of the 

regulatory framework and then turn to specific aspects of the study. 

In terms of the statuary framework, EPA regulates pesticides under the Federal 

Insecticide, Fungicide, and Rodenticide Act (FIFRA). FIFRA requires that every pesticide

product sold in the United States undergo an approval process called registration. The 

registration process addresses composition, labeling and packaging separately. Composition 

includes a defined statement of the formula (i.e., the percentage of active and inert ingredients) 

as well as the type of formulation (e.g., liquid, dust, granule, gas). EPA spends most of its time 

on the labeling of pesticides. Each pesticide product contains labeling—that is, written 

instructions for use. These directions define target pests as well as the method of mixing and 

application information (loading, quantity, frequency and when to apply). In addition, warnings 

and cautions are associated with applying the product. Instructions also are included regarding 

special equipment, especially personal protective equipment (PPE). Other limitations, such as 

restricted harvesting intervals and requirements for the planting of different crops in the future 

year, also are described. All instructions are important because it is unlawful to use pesticides 

inconsistent with the labeling. The labeling is the law and guides the understanding of how a 

pesticide is to be used. Packaging concerns the container size, composition and other 

characteristics but generally is not regulated. 

After EPA procures the information on composition and labeling, it then determines if the 

pesticide can be sold in the marketplace based on whether there are unreasonable adverse effects 

to the environment. The registration standard considers both the risks and benefits of using the 

pesticide. Pesticides provide a useful purpose to the consumer but are biologically active and 

also can pose risks. EPA makes a decision on whether the benefits of using the pesticide 

outweigh the risks; most of its focus concerns risk, which is a function of toxicity and exposure.

EPA considers a wide range of potential risks, both to human health and the environment, 

that arise from pesticide use. These risks include occupational, dietary, bystander and residential 

risks. Occupational risks include the handlers or workers that apply or work around applications 

of pesticides. Dietary risks include residues in food, and the objective is to ensure that foods are 

safe to eat. Bystander risks become important when pesticides that are applied outdoors move 

beyond the intended site and affect those nearby. There also are risks for people in residential 

settings (e.g., schools, office spaces).
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Mr. Jordan stated that the completed study under review generated data for use in 

occupational risk, particularly for two categories: handlers and workers. Handlers are people who 

mix, load or apply pesticide products to the environment or home. Workers enter the area where 

the pesticide was applied and are exposed as a consequence of work activities to the residues that 

remain following the application. Handler exposure depends on three elements: 

(1) How the pesticide is mixed, loaded and applied. Research aims to derive “unit 

exposure,” that is, the amount of an active ingredient in the pesticide that a person will be 

exposed to while performing certain activities, and normalizing that amount of exposure to the 

amount handled. The handling scenario is a particular set of activities by the handler that is 

described by the type of pesticide (e.g., dust, wettable powder) and the activity of the person 

(e.g., mixing, applying, loading). Sometimes the scenarios vary according to equipment, as the 

type of application equipment can make a difference in the handling scenario. A person’s 

exposure to an antimicrobial product applied to a floor might be different depending on whether 

a mop was used or a trigger spray bottle followed by wiping with a rag or sponge.

(2) How much of the pesticide is handled. We assumed that the more pesticide is 

handled, the more exposure will occur. This is why the unit exposure usually is normalized to the 

active ingredient, followed by an examination of how the active ingredient is handled.

(3) The impact of using PPE. The exposure to a person is affected by the clothing and 

PPE (e.g., chemically resistant gloves, apron, respirator) that are worn.

Mr. Jordan next described data sources for estimating occupational exposure. For unit 

exposures, studies with surrogate chemicals that measure inhalation and dermal exposure to the 

handlers’ body during the activity are considered. Dermal exposures are measurements of 

residues on different parts of the body; for inhalation exposure, an air monitor collects residues 

in the breathing zone of the handler. A surrogate chemical is used because it is assumed that the 

exposure does not depend on what active ingredient is in the pesticide. Which chemical is used 

to mop a floor is less important than how the floor is mopped with water containing the 

chemical.

With regard to the amount of active ingredient handled (AaiH), EPA monitors the 

estimate at the higher end of exposure. Regarding mopping, for example, desired data would 

include the number of hours that a janitor or hospital orderly might spend mopping floors during 

a normal day’s work, followed by an analysis of how many gallons of water-mop mixture that 

person used per hour. Finally, the pesticide label would be examined to ascertain how much 

active ingredient would be in each gallon of mop water. These values would be multiplied 

together to obtain the high-end estimate of the amount of active ingredient that a person is 

handling while performing the daily task.

Mr. Jordan discussed the impact of PPE. Data sources indicate the reduction of a certain 

percentage of exposure by inhalation if someone wears a respirator; similarly, the residue on the 

hands will be reduced by a certain percentage if one wears chemically resistant gloves. All of the 
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datasets are pooled to develop an estimate of the high-end exposure of the handler performing a 

task with a particular product.

The concept of unit exposure was described. The common-sense approach assumes that 

the more pesticide a person handles, the more exposure a person can get. A representative study

ascertained individual exposure to varying amounts of pesticide. These data showed that the 

exposure rises as the AaiH increases. The data reflect that some people are more careful than 

others in handling pesticides; inter-individual variability is addressed through taking the unit 

exposure and finding the mean of the different values, and applying these across the data. By

using conservative values for other components of the exposure, the estimate reaches the highend values to represent handler exposure. Although the current discussion will consider a dataset 

that looks different, this historical dataset can be used in a way to provide a conservative 

estimate of high-end exposure.

Mr. Jordan advocated the use of proportionality analysis. If the unit exposure was not 

used to normalize to the AaiH, there would be many more studies required. The surrogate 

pesticide notion allows one to extrapolate from one study to many different active ingredients 

that are mixed, loaded or applied using the same techniques. Additionally, data are not needed 

regarding application rates and pesticides in the product. From the standpoint of practicality and 

reducing human exposure, as well as making it possible to conduct risk assessments efficiently, 

the notion of proportional unit exposure makes sense. One should recognize that when the line of

lognormal plots of data is not exactly 1 in terms of slope, this may lead to an underestimation of 

exposure at lower AaiH and overestimation of exposure at higher AaiH. From a policy

perspective, this is an appropriate, acceptable error because regulators do not base risk decisions 

on estimates of risk that are too low. If a decision that is based on too high a risk estimated under 

real-world conditions is acceptable, then the lower value also would be acceptable. Mr. Jordan 

proposed that errors introduced under the notion of proportionality are an acceptable way to 

approach the assessment of exposure.

Board Questions

Dr. Parkin asked Mr. Jordan to expand on the concept of what constitutes an acceptable 

surrogate and what types of criteria to consider or judge if a specific surrogate is an appropriate 

representative chemical of interest. Mr. Tim Leighton (OPP, EPA) responded that when looking 

at data from a surrogate, the use should be fully representative to ensure that the actual scenario 

(e.g., how people are exposed) is covered. Additionally, EPA uses a cutoff of 10-4 millimeters of 

mercury (mm Hg) for the vapor pressure of surrogates; any higher vapor pressure must be 

accounted for by considering the worker’s perspective. Further volatility (e.g., 10-3or 10-2 mm 

Hg) increases the exposure to both the aerosol measured in the studies and anything that is 

volatilizing. An examination would include the aerosol exposure as well as monitoring data or 

models to estimate the air concentration. The toxicity study itself also could be evaluated to 

determine whether vapor inhalation toxicity data were generated. Dr. Parkin thanked 

Mr. Leighton for his response. 
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Dr. George Fernandez observed that the diagram (Slide 8) shown by Mr. Jordan was 

meant to show proportionality, but there is a point that clearly shows there should be a nonlinear 

effect; studies usually show linear effects but not always. 

Mr. Leighton clarified that when using surrogate data for a risk assessment, chemicalspecific dermal absorption and toxicity information are considered. 

Dr. William Popendorf commented that extrapolation in practice is said to be primarily 

from one chemical to another based on the concentration of the chemical in the product versus 

two products with the same concentrations. He wondered whether it happens that the amount one 

uses is substantially different between the two situations. Mr. Leighton replied that EPA 

considers both situations. For example, when homeowners use trigger spray pump pesticide 

products, what changes the AaiH is the concentration. A product with a 10-fold higher 

concentration might increase exposure. Dermal absorption of the chemical is another 

consideration. For someone in a hospital who uses much more product to clean operating rooms, 

the concentration would be the same but the volume would be much higher. In those instances, 

the volume would be indicated. It would have been useful to consider various concentrations 

(e.g., 0.2 to 20 percent) in the current study, but it would have required a separate study because 

it is not ethical to expose people to high concentrations of pesticides without chemical-resistant 

gloves or respiratory protection. That is one limitation to the design of this study, which will be 

discussed further.

Dr. José Manautou requested clarification that for concentrations over 20 percent, PPE 

would be required in exposure studies. Mr. Leighton responded that the ethical concentration 

cutoff is dependent on the chemical used. For example, quaternary ammonia compounds are 

irritants only at high concentrations greater than 10 to 20 percent. 

Session 1: A completed study report from the AEATF in which the dermal and inhalation 

exposure of professional janitorial workers was monitored as they poured liquid 

antimicrobial pesticide products from conventional or reduced-splash containers into 

different sizes and types of receiving containers.

Background

Dr. Parkin introduced the AEATF study as one that the Board had reviewed in October 

2011 and had a number of recommendations for the protocol. The Board is charged today to 

review the completed study and evaluate whether it met scientific and ethical expectations. Dr. 

Parkin asked Mr. Leighton to present the Agency’s review of the scientific aspects of this study. 

Board members would then be provided an opportunity to ask clarifying questions.

EPA Science Assessment

Mr. Leighton welcomed the meeting participants. He remarked that this HSRB meeting 

was to be held on November 1, 2012, but was canceled because of Hurricane Sandy. 

Mr. Leighton explained that the AEATF is comprised of 44 chemical companies that leverage 
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shared resources to accomplish the exposure studies mandated during the 2006 Science 

Advisory Panel (SAP) and 2007 HSRB meetings. EPA, Health Canada and Cal/EPA comprise a 

Joint Regulatory Committee (JRC) to review intentional human exposure studies. During the 

most recent convening of the Board in January 2012, the members had evaluated a completed 

AEATF study similar to the completed study on the agenda today.

Mr. Leighton presented EPA’s review of the completed AEATF liquid pour study , 

which consisted of dermal and inhalation monitoring of workers pouring a liquid antimicrobial 

product from various size containers packaged in conventional and reduced-splash containers. 

Mr. Leighton explained that he would present EPA’s science review, and Ms. Kelly Sherman 

(OPP, EPA) would present EPA’s ethics review. Dr. Jonathan Cohen (ICF International), the 

contractor statistician integral to EPA’s review efforts, was present by telephone to answer any

questions. 

Mr. Leighton noted that this fifth completed AEATF study was the most complex to 

date. He provided an overview of his presentation, which consisted of a description of the study, 

explanation of the AEATF’s responsiveness to EPA and HSRB comments, outline of three main 

issues highlighted in EPA’s science review, and conclusions. Mr. Leighton acknowledged that 

although the issues were challenging, the path forward to address each one was clear.

This liquid pour scenario was one of 17 AEATF scenarios, which also includes exposure 

studies evaluating mopping and the use of sprays and wipes, to evaluate antimicrobial products 

typically labeled for disinfectant use. The 17 scenarios originally were to be completed within 

5 years, but that timeframe has been extended. The liquid pour study was completed indoors 

using two scenarios: conventional pour (CP) and reduced-splash (RS) containers. The product 

and receiving containers were of various sizes. For example, the receiving containers ranged 

from 2 gallons to 50 gallon troughs (e.g., for industrial applications). This study specifically

monitored pouring events; the workers did not apply the treatment solution.

Although other studies occur in randomly selected buildings, a laboratory in Concord, 

Ohio, was selected for this study to reduce costs; this was not ruled to affect the overall use of 

the data. Monitoring was conducted in two rooms. Each subject was monitored once for CP and 

once for RS containers to produce two distinct monitoring sets. To ensure a diversity of 

individual exposures, one enrolled subject was assigned to each of six monitoring events (ME) 

in a group that was defined by the size of the product container for a total of three groups. There 

were 18 ME for CP and 18 for RS. The receiving container type, height (floor or chest-height) 

and use of a measuring cup also varied.

Dermal and inhalation exposure was monitored for six subjects in each of the three 

groups (18 total). CP containers contained didecyl dimethyl ammonium chloride (DDAC), while 

RS containers contained n-alkyl dimethyl benzyl ammonium chloride (ADBAC). This enabled 

the use of fewer test subjects to capture more information. Subjects wore inner whole-body

dosimeters (WBD) as well as dosimeters outside of the clothing. No gloves were worn. Subjects 

wore Occupational Safety and Health Administration (OSHA) Versatile Sampler (OVS) tubes 

on their lapel to capture the breathing environment. Particle size was not measured.
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Mr. Leighton presented a table (Slide 7) depicting the various MEs. He explained that 

although the original protocol had considered three separate groups, upon review of the results 

group 1 was divided into 1a and 1b to account for the differences of pouring into bottles. A CP 

container is similar in structure to a milk jug, while an RS container is engineered to reduce 

“glugging” through the addition of an extra spout. The inclusion of RS containers in the 

scenario was intended to determine whether engineering controls would decrease exposure and 

obviate some of the need for PPE. Product labels do not regulate the size of containers sold, so 

the researchers included a diversity of sizes in the study protocol, ranging from 24 ounces (oz) 

to 5 gallons, to represent what is available on the market. The subjects poured a specific number 

of product containers per ME (e.g., 10 containers poured per ME when the receiving container 

was 32 oz spray bottles or six 5 gallon buckets into the 50 gallon trough). Mr. Leighton 

reminded participants that the efforts of each individual subject could be found in Table 2 of the 

EPA Science Review and Tables 7 and 8 of the AEATF study report. 

Mr. Leighton presented several photographs depicting the study scenario. The first 

photograph (Slide 8) showed a subject pouring from a gallon container into a measuring cup. 

The second photograph (Slide 9) illustrated a subject pouring liquid into a spray bottle with a

visible spill down the bottle. Observational notes indicated that the spill contacted the subject’s 

hand. Spills and drips happened frequently despite the professional janitorial background of the 

research subjects. This demonstrates that pouring liquid is not a highly trained skill, as spills 

happen even in a randomly selected janitorial population, and suggests that the data would be 

applicable to consumers as well as janitors. The next photograph (Slide 10) depicted a Group 2 

ME where a subject poured from a 1 gallon container into a 4 gallon bucket at chest height. The 

remaining photographs (Slides 11-13) illustrated subjects pouring liquid into a trough with CP 

and RS containers. Prior to the study, investigators did not know whether RS would make a 

difference, so they were interested in looking at that variable.

The stated objective was for the liquid pour study to provide sample estimates of the 

arithmetic mean and 95th percentile of normalized exposure accurate to within three-fold, 

95 percent of the time. Thus, the reviewers used a K-factor goal of three-fold relative accuracy

in judging these data and sought an arithmetic mean that was within three times the lower and 

upper 95th confidence intervals. 

Mr. Leighton described the responsiveness of the AEATF to EPA and HSRB comments. 

Prior to the HSRB evaluation, the JRC had worked with the AEATF to help submit the study to 

the HSRB. EPA and the HSRB then provided additional comments to improve the clarity and 

design of the study, recommending the inclusion of more random procedures and 

acknowledgement of design limitations (e.g., janitor versus consumer population, indoor versus 

outdoor). For example, there could be differences in the data if the study was performed 

outdoors. The AEATF responded to each specific comment to EPA’s satisfaction.

Mr. Leighton lauded the AEATF for the few and minor protocol deviations, remarking 

that many deviations used to occur in these studies and there has been great improvement. Nine 

deviations were reported, including an uncalibrated bathroom scale, and there were no 

unreported deviations. EPA concluded that the deviations in the study do not affect the 

scientific validity of the use of the exposure results. 
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A diagram of a WBD was presented to demonstrate how the WBD could be sectioned to 

measure dermal exposure for a variety of clothing scenarios: long shirts/long pants (long-long), 

long pants/short shirts (long-short) and short shirts/short pants (short-short). After the ME, 

researchers removed the WBD and sectioned it into pieces; this provided another method to 

limit the subjects involved in the study.

Mr. Leighton explained that hand exposure was the primary driver in each exposure 

scenario. All laboratory and field blank samples were less than the limitation of quantitation 

(LOQ), and individual laboratory recoveries ranged from 75 to 116 percent. The field recoveries 

were used to correct dosimeters. Importantly, a stable surrogate chemical was chosen that would 

not be photo labile or otherwise degraded by laboratory conditions, which would result in 

underestimation of exposure. The mean recovery of all samples was approximately 90 to 100 

percent, with four recovery samples falling outside of 70 to 120 percent (64, 67, 174 and 178 

percent). The two highest values were not used to correct the field samples because there was a 

problem with the fortification. A 90 percent field sample recovery would mean that 10 percent 

was lost somewhere in the process, and a 10 percent correction would be applied the laboratory

samples.

Subjects were instructed to work as they normally would to increase the random elements 

within the study. The mean amount of AaiH was 0.16 pounds (lb) for CP and 0.14 lb for RS 

containers. Mr. Leighton allowed that it would be interesting to have a wider range of AaiH 

within the protocol, but that was not possible given the need for PPE, specifically gloves, at 

higher levels of active ingredient. Most people pouring these liquids under normal 

circumstances do not use gloves. The time to pour varied by individual, with an average of 

8 minutes for CP and 13 for RS containers. Subjects poured approximately 4 oz of liquid at a 

time into 10 to 15 bottles, or 30 gallons in 5 gallon increments.

Three methods were used to estimate unit exposures, including the empirical estimate, 

simple random sample (SRS) and mixed model. Empirical estimates are easy for people to 

understand and are presented in the docket, while the more complicated statistical models are 

contained within Tables 3 to 6 of the EPA Science Review. Following the 2006 SAP discussion, 

the mixed model was selected to best represent the unit exposure results. Mr. Leighton invited 

Dr. Cohen to give an explanation of the SRS versus mixed model results.

Dr. Cohen explained that all formulae were listed in Table 7 of EPA’s Science Review

and additional details could be found in Appendix A of EPA’s Science Review. He remarked 

that for the empirical model, the geometric and arithmetic means were calculated separately for 

each group by taking the sum of exposures divided by the number of values. The geometric 

mean is the same for the simple lognormal model, but the arithmetic mean is calculated assuming 

a lognormal distribution, which includes multiplication by half of the variance. This results in a 

different estimated arithmetic mean than for the empirical model. Finally, the mixed model uses 

lognormal distribution but incorporates a random worker effect variable because the same 

worker tested CP and RS containers, which could occur in either order. It is likely that 

correlation exists between those two measurements, and the mixed model accounts for that 
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correlation. The geometric and arithmetic mean have different values, as does the geometric 

standard deviation. 

Mr. Leighton remarked that the summary results of Table 1 in the EPA Science Review 

do not match Tables 3 through 6 because the calculations were performed using the mixed and 

empirical models. All models can be compared in the review’s appendix.

Mr. Leighton highlighted three data issues identified by EPA. First, as already discussed, 

there were three rather than two distinct exposure scenarios. Second, the results were atypical for 

the clothing configurations, and third, there was an unexpected negative slope for dermal 

exposure. 

Although the AEATF designed the liquid pour scenario to address two distinct exposure 

scenarios (CP and RS), after reviewing the results, EPA separated the results into three distinct 

exposure scenarios: bottle (i.e., using a spray bottle as a receiving container), CP into non-spray

bottles and RS into non-spray bottles. This resulted in six MEs for Group 1a (bottle), which 

combined CP and RS events for the analysis. Other than bottles, the CP results were combined 

for all groups (15 MEs) and the RS results were combined for all groups (15 MEs). Mr. Leighton 

explained that these groups fell out logically and statistically after p values were calculated for 

various options. Grouping the bottles was logical because disinfectants often specify the use of 

spray bottles on the label, so the data from this scenario could be used specifically for spraying. 

The bottle group was a statistically justified unit exposure because the Groups 1a CP and 1a RS 

were not significantly different, while bottles compared to other receiving containers were 

significantly different for the two container choices. The p values of all combinations, as well as 

a summary of the statistics, are available within the EPA Science Review document. 

The second issue addressed the fact that the results were atypical according to the

clothing configurations. Each subject wore two WBDs, which were parsed into long-long, longshort and short-short configurations. This was done to account for the maximum exposure 

potential to a consumer, who might be wearing a short shirt and short pants. Janitors might wear 

a short shirt and long pants or a long shirt and long pants. Because the disinfectants are not 

irritants at low doses, there are no PPE requirements on the labels. The results were atypical in 

that more clothes resulted in a higher exposure; the unit exposure for the mixed model mean is 

greatest for the long-long configuration. The atypical results might be more understandable if a 

person were taking used gloves on and off, as they might get a higher exposure, but this did not 

occur. For CP container MEs, the mean was 10 for long-long, 9.9 for long-short, and 9 for shortshort in units of milligrams (mg) per lb of active ingredient. Although these differences are

small, the results are illogical and might result from a statistical quirk of the mixed model. 

Mr. Leighton emphasized that hand exposure accounts for the majority of the dermal exposure. 

Because of these atypical data, EPA will only consider the long-long configuration (the highest 

exposure data) when applying the results. Mr. Leighton referred participants to page 4 on the 

EPA Science Review for further explanation about these atypical results. 

The third issue, Mr. Leighton explained, was the negative slope for dermal exposure. At 

the end of the January 2012 meeting, the Board members decided to explore options other than 

proportionality. The log-linear regression model postulates that the log of the exposure equals the 
13

intercept plus the slope times the log of the AaiH plus error. If the slope equals 1, exposure is 

proportional to AaiH. If the slope is 0, exposure does not vary with AaiH, which is physically

unrealistic because a worker is likely to spill some volume of the product on his or her hands, 

and a higher concentration of product would result in more exposure. If the slope is less than 0, 

this suggests that exposure decreases with AaiH, which also is unrealistic. Thus, the discussion 

about the volume poured and the concentration is relevant. The data in this scenario revealed a 

negative slope of -0.3 for the long-long configuration. As discussed, this is not a realistic result 

because pouring more product likely results in more spilling and thus a higher exposure. It is 

possible, however, that the random nature of spills accounts for the negative slope.

When EPA researchers saw these data, they first sought outliers as an explanation. 

Outliers would not be discarded, however, because the data represent someone using a pesticide 

as he or she usually would and spills occur in routine use. The slope did not change, however,

even when outliers were removed. When the slopes were calculated separately for each scenario, 

all slopes remained negative. Although the inhalation data were more realistic, the data for 

dermal exposure showed a negative slope no matter how they were handled.

For the application of unit exposures, EPA will normalize the liquid pour data by AaiH. 

Logically, each drip or spill on the hands is a given volume of liquid and the exposure is 

dependent on the concentration of AaiH, which is calculated by the volume poured times the 

concentration. This relationship would be the same for residential use of pesticides as it would be 

for a hospital worker. Mr. Leighton explained that this approach is protective of human health. 

There are ways to characterize the limitations in the data using the threshold of AaiH to 

determine whether exposure will be under- or over-predicted. During the protocol evaluation 

stage, Dr. Michael Lebowitz had remarked that because people spill liquids, the AEATF might 

want to consider adding different concentrations to the protocol. Because of the need for 

chemical-resistant gloves when using higher concentrations, however, additional concentrations 

of AaiH were not included because a different scenario would have been required. 

Mr. Leighton presented the unit exposures for the liquid pour scenario. The bottle 

subgroup displayed an arithmetic mean of 299 mg/lb active ingredient for dermal exposure

(using long-long exposure data), while the CP and RS had much lower exposures of 10 and 

3.1 mg/lb, respectively. Thus, the RS container lowered exposure by three-fold. With regard to 

inhalation exposure, the low vapor pressure of the chemical (10-6 to 10-8 mm Hg) meant that none 

of the samples were lost to volatility. The workers wore OVS tubes in the breathing zone to 

sample the full air environment. The samples could be normalized to mg/lb of active ingredient

because sometimes there are oral endpoints without inhalation route-specific studies. This 

provides one method to do a route-to-route extrapolation, although the Agency is trying to move 

away from this. The results also show a time-weighted average of 8 hours, although any other 

time span could be calculated. The values are small because the pours are just 10 minutes long. 

Mr. Leighton noted that EPA did not have sufficient time to use values other than half of the 

quantification for the nondetected samples, so the values presented in EPA’s Science Review are 

slightly different. When other multiple computation methods were applied to handle the 

nondetected samples after the HSRB review was postponed due to Hurricane Sandy, the bottle 

estimates decreased by 80 percent while the CP and RS scenarios increased by 10 or 20 percent. 

Approximately 40 percent of the samples were not detected.
14

To address the question of whether the sample was large enough, Mr. Leighton presented 

the K factors for each group. The three-fold relative accuracy goal was met for all three 

inhalation scenarios (bottle, CP and RS). For dermal exposures, the K value was less than three 

for CP and RS but not for the bottle, although the value was close (ranging from 3.1 to 3.6). EPA 

will use all of the results from this study at this point. The bottle results will be used because if 

the bottle results were to be combined with CP and RS, the disinfectant uses would be 

underestimated and all other uses would be overestimated. After all of the 17 planned AEATF 

studies are completed, there may be a need to refine the bottle unit exposure with additional 

monitoring. The current bottle results could be combined with CP and RS as designed, but 

logically it is better to separate those results. 

The study design limitations were discussed previously during the protocol review of the 

HSRB and many are the same as those identified at the completion of the study. Study

limitations include indoor versus outdoor use and janitor versus consumer use. The impact of 

pouring liquids indoor versus outdoor on exposures is unknown and would be expensive to 

determine. Most products are poured indoors. The exposure impact also is unknown for 

consumers versus janitors, but it is reasonable to use the data for both populations because as 

seen from the photographs, pouring liquids is not a highly skilled task and even professional 

janitors spill products.

Another design limitation is that the relative accuracy goal for the bottle scenario was not 

met. It is logical to use these data, however, because they are health protective. Normalizing 

dermal exposure by AaiH is another limitation. The threshold of AaiH characterizes when 

exposures are under- or over-predicting. It would have been useful to vary the concentration 

data, but this was not feasible. Another design limitation is that only the long-long clothing 

configuration data could be used. The amount of product that spilled on the subjects’ hands was 

the driver of exposure. In the future, measuring only hand exposure is worth consideration to 

reduce study costs.

EPA plans to use the liquid pour study data generically to estimate the potential exposure 

to low- or moderate-volatility pesticides packaged as liquids for open pouring. Mr. Leighton 

explained that 10-4 mm Hg is low volatility. If a product has a higher volatility, exposure to 

aerosols will be a concern and the vapor phase would need to be accounted for or modeled

separately. Disinfectant and sanitizer uses that include spray bottle type applications will use the 

bottle unit exposure scenario data. Mr. Leighton noted that the majority of assessments are 

performed using CP containers. The opportunity exists to reduce exposure if the industry adopts 

RS packaging; the JRC could support the use of RS containers. 

In conclusion, EPA determined that the study results were sufficiently sound to support 

estimates of dermal and inhalation unit exposures. An adequate number of samples were 

collected for CP and RS; therefore, no additional MEs are required. Additional monitoring of the 

bottle scenario, however, might be warranted to refine the estimates. These data will be used now 

because the exposures are justified logically and statistically. EPA will know when to use the 

bottle estimate based on the label claims. EPA already recalculated the inhalation unit exposures 

using the multiple imputation method for nondetected samples. Importantly, data limitations
15

must be acknowledged in any assessments. Mr. Leighton offered to answer any questions 

regarding EPA’s science review. 

Board Questions of Clarification—Science

Dr. Parkin asked Board members if they required any clarifications. Dr. Dallas Johnson

questioned whether the arithmetic mean resulted from transforming the lognormal mean back 

into the arithmetic mean. Mr. Leighton clarified that the arithmetic mean and 95th percentile 

were estimated from the results of the mixed model. The confidence intervals on each estimate 

relevant to the K factor are shown in Table 1 of the study review. 

Dr. Linda Young asked which equation was used to calculate the maximum likelihood for 

substituting half-nondetects. Dr. Cohen explained that the equations were described in the 

appendix of the EPA Science Review. The investigators know that the values for inhalation 

exposure are between 0 and the detection limit. Dr. Young asked whether the EM algorithm was 

used because imputation depends on the parameters of the model, which in turn depend on the 

imputed value in an iterative process, and EM is one common method to use. Dr. Cohen 

explained that the calculation was performed by maximum likelihood in SAS, as SAS does not 

use the EM algorithm. He stated that the calculation is a similar algorithm, however, to find the 

maximum likelihood of the fitted model. Dr. Young mentioned that she saw imputation for 0 or 

one-half but did not see multiple imputation in the EPA Science Review models. She asked 

whether the SAS programming used PROC PMI. Dr. Cohen remarked that the program shows 

“percent macro impute.” Where imputation occurred, the SAS mixed model and a nonlinear 

mixed procedure were used.

Dr. Young referenced three equations on page 36 of the appendix for her next question. 

Dr. Cohen confirmed that the “exposure equal” and “arithmetic mean exposure equal” were

intended to follow the preceding line, and that the pounds of active ingredient would follow from 

those two equations. The arithmetic mean is the exposure given the amount of active ingredient. 

Dr. Young remarked that the equation was conditional on the pounds of active ingredient, which 

was not constant throughout the study.

Dr. Leonard Ritter noted that Mr. Leighton’s presentation had indicated that two low and 

high values were rejected. Mr. Leighton clarified that only the two highest values were rejected

because exposures are not corrected down if the whole average was above 100 percent. Dr. Ritter 

asked at what point when correcting for field recoveries are the data no longer trusted. 

Mr. Leighton responded that if two numbers were extreme, such as 0 percent and 200 percent 

that would indicate that the data should not be trusted. Precision also is important; if field 

recoveries were 28 to 34 percent and the coefficient of variation was good, the data would be 

used. Numbers are not discarded if they are precise. The surrogate choice is another 

consideration. If field recoveries show that only 30 percent of the sample is captured, the 

AEATF might pick a different surrogate. Compounds are selected that provide quality analytics 

and are not photo labile or otherwise susceptible to loss. Dr. Ritter remarked that the outliers 

might indicate that the surrogate is not the best fit in this instance. 
16

Dr. Ritter asked how much of the exposure was driven by the hands relative to the 

remainder of the dermal exposure. Mr. Leighton responded that up to 98 percent of the exposure 

could be related to hand exposure. Dr. Ritter acknowledged that the effort and cost was 

significant to capture all dermal exposure. Hand exposure could be reduced by such efforts as 

wearing new gloves. Mr. Leighton mentioned that Board members had discussed whether just 

hands and inhalation should be monitored. The Pesticide Handler Exposure Database (PHED)

also indicates that hands are a driver of exposure. This universal experience should be noted for 

future studies; resources previously allocated for dermal exposure could instead be applied to 

quality assurance and control. 

Dr. Popendorf clarified that hands and face exposure were measured. He then asked 

whether any data existed regarding the use of spray bottles for janitors or custodians. 

Mr. Leighton answered that a consumer industry task force investigated which products are 

applied with what type of applicator (e.g., mop, aerosol can, trigger spray pump) and at what 

percentage. He remarked that the AEATF would be interested in investigating trigger spray

pumps even if they were used 1 percent of the time. The information is available.

Dr. Popendorf remarked that the study subjects poured the liquid 10 to 15 times and 

wondered whether that happened in the real world. Mr. Leighton responded that hospital 

operating room custodians do pour liquids at that high of a volume. If only one bottle had been 

used per ME, dripping might have been missed. In response to a question, Mr. Leighton clarified 

that drips were not cleaned between pours, and no rag to clean the bottle was provided. 

Additionally, subjects were permitted to decide whether they would pour water or the product 

first into the container.

Dr. Popendorf referenced the comment in the report that stated that handling chemicals 

indoors resulted in a higher exposure than outdoors and asked for an elaboration. Mr. Leighton 

acknowledged that the statement was very broad and did not apply in such situations as when a 

liquid was poured outside and the air was blowing back into the handler’s face. 

Dr. Popendorf remarked that the report indicated that the air flow direction and subject 

orientation was to be monitored and questioned whether those data were included in the report. 

Mr. Leighton clarified that the laboratory was preset so the subjects could not change orientation. 

The researchers could help to clarify the direction in which the subjects were facing as they

poured the liquids. 

Dr. Popendorf acknowledged that all Board members agreed that concentration data 

could not be used at times. Because of the 40 percent of nondetect samples, he supported the 

monitoring of hands alone if there was a big enough spread of concentration. A 10-fold range 

might be enough, although three orders of magnitude would be preferable.

Dr. Sidney Green asked a question regarding the formulae for calculating unit exposure

through the input of specific chemicals in relation to toxicologic endpoints of concern. 

Specifically, he was interested in how those studies would be conducted with the number of 

endpoints and dosages with each study. That information is not found in guidance documents. 

Mr. Leighton remarked that Dr. Green’s question was outside of the scope of the science review, 
17

but responded that regulatory authorities had the ability to use toxicity data, animal data, 

observational, and OSHA data that show when a sensory irritant elicits its peak effect. The 

exposure limit can be hit within a given timeframe. Dr. Green asked how the assessors decide 

which studies to use if limited to two to three dermal toxicity studies. Mr. Leighton responded 

that investigators choose between tier 1 and tier 2 toxicologic testing and 90-day oral and dermal 

studies. After consulting the database of studies, a committee of toxicologists collectively

decides to take the lowest level of concern for uncertainty factors, which could result in a 100- or 

1,000-fold uncertainty factor. The lowest level of concern from the group of studies, as well as 

other documents, determines how endpoints are selected.

Dr. Manautou questioned whether the sequence of pouring water and product was 

recorded for each subject. Mr. Leighton responded affirmatively and remarked that most subjects 

poured the product first. Dr. Manautou wondered whether the sequence might have affected the 

exposure. Later, Mr. Leighton clarified that all but one test subject poured the product before 

pouring the water. The one person who had begun pouring the water first switched the sequence 

during the ME. 

Dr. Manautou asked whether spray bottles always were used for disinfectant purposes. 

Mr. Leighton responded that is not always the case, but usually a trigger spray pump is used for 

disinfectants. Newer labels indicate whether the product should be used with a mop, wipe or 

spray. Furthermore, the investigators did not know ahead of time that the results would be so 

different for the bottle MEs. 

Dr. Parkin asked the Board whether they had any further questions or clarifications. 

Seeing that there were none, she asked Ms. Sherman for the Agency’s ethics assessment.

EPA Ethics Assessment

Ms. Sherman stated that the AEATF protocol was reviewed by the HSRB in October 

2011. The sponsors consented to address the HSRB comments and revised the protocol 

accordingly. The revised protocol was sent back to the approving Institutional Review Board

(IRB) in January 2012, at which point recruiting and subject enrollment began. Monitoring 

occurred in February 2012, and the report was submitted to EPA in August 2012. 

Subjects were recruited through advertisements in three local newspapers, including the 

News-Herald of Northern Ohio, the Star Beacon and La Prensa (a weekly bilingual 

English/Spanish publication). Most of the calls were in response to the advertisements in the 

News Herald. Interested callers were phone interviewed by an IRB-approved script to determine 

whether they met the inclusion criteria (e.g., prior janitorial experience, at least 18 years old, 

sufficient fitness to lift a 40-lb bucket). If the callers met the study criteria, they were scheduled 

for an informed consent meeting. Ms. Sherman explained that recruiting was consistent with the 

protocol, and the process was equitable and free of coercion or undue influence. In particular, 

placing the advertisements in various newspapers targeted different groups to minimize bias and 

achieve diversity. 
18

The study director held initial consent meetings with small groups of potential subjects 

to explain the study procedures, describe inclusion and exclusion criteria, read the consent form, 

and answer questions. People were encouraged to ask questions and take the materials home to 

discuss with their friends and family. If a subject met the inclusion and exclusion criteria and 

was still interested in enrolling, he or she met one-on-one with the study director. Given that the 

subject was deemed to possess a good understanding of the materials, he or she was asked to 

sign the informed consent form (ICF) and was then considered a subject. Of the 22 people 

scheduled for one-on-one meetings with the study director, 20 were enrolled. One person 

decided not to move forward with the process, and another person was excluded because he or 

she was the spouse of someone who worked at the laboratory. Two people on the standby list 

went through the consent process, which brought the total to 22 enrolled. Ms. Sherman 

concluded that the consent process closely followed what was outlined in the protocol and was a 

good process. No deviations related to the consent process occurred.

Ms. Sherman described the subject demographics. Of the 18 subjects monitored, 15 were 

male and three were female. The mean age was 48 years. While all subjects possessed at least 

1 year of janitorial experience, the mean years of experience was 12. All subjects preferred to 

speak in English.

When the subjects arrived at the study location, they were reminded about the details of 

the study and informed that they could withdraw at any time. Prior to dressing with the 

dosimeters, each subject was introduced to a medical professional (nurse or emergency medical 

technician) who examined the hands and face to ensure that no broken skin or sores existed to 

act as excluding factors. The three females self-administered a pregnancy test. After doing so, 

they were asked whether they still wanted to participate, and if they answered affirmatively, the 

study director confirmed that the test was negative. Researchers helped each subject put on the 

dosimeter, which was washed prior to use, as well as the air-sampling pump. 

Ms. Sherman reminded the Board members that spillage occurred during the study, but 

this did not raise concern about the subjects’ safety from an ethical standpoint because pouring 

liquid chemicals into bottles and troughs was a normal activity. There was no concern in terms 

of risk, and the study was conducted without noteworthy incident. None of the subjects felt sick 

or were injured during the monitoring. Subjects were told that they could take a break at any

time and were given a break when switching from CP to RS containers, at which point they

were offered a drink. In general, the conditions were undemanding. There was nothing ethically

concerning in the notes taken by observers. 

Ms. Sherman explained that in terms of responsiveness to the EPA and HSRB protocol 

reviews, the investigators did everything asked of them. Most of the Board’s ethical qualms 

were related to improving the clarity of the ICF, and all of the changes were made.

The initial protocol was approved by the Independent Investigational Review Board, Inc.

(IIRB) in August 2011. The study directors complied with all IIRB procedures and requirements 

in revising the protocol, which was approved by the IIRB in January 2012. Five amendments 

were approved by the IIRB, and five deviation reports were reviewed and acknowledged by the 

IIRB. None of the reported amendments or deviations was ethically significant and no 
19

unreported deviations were found. One deviation involved the sequence of shoe removal. 

Originally, subjects were to remove their shoes after taking off the sampling pipe and hand 

wash, but this order was reversed to minimize contamination in the room. This deviation did not 

affect the ethics. The documentation of IIRB correspondence was complete and well-indexed. 

The requirements of 40 CFR §26.1303 for the documentation of ethical conduct were complete 

and satisfied. 

Ms. Sherman concluded that the study met the substantive acceptance standards of 

40 CFR §26.1703, 40 CFR §26.1705 and FIFRA §12(a)(2)(P). All subjects were at least 18 

years old. There were no noteworthy deficiencies in the ethical conduct of the research, the 

protocol was faithfully executed as amended, and minor deviations did not compromise the 

safety of the subjects. Subjects were fully informed and consented to the study without coercion 

or undue influence. 

In conclusion, Ms. Sherman reported that the available information indicates that the 

AEATF Liquid Pour Study was conducted in substantial compliance with subparts K and L of 

40 CFR part 26.

Board Questions of Clarification—Ethics

Dr. Parkin solicited clarification questions from the Board members and none were 

proffered. 

Public Comments

Dr. Parkin called for any public comments. Mr. Downing remarked that no public 

comments had been registered in advance. However, one member of the audience spoke up and 

wished to address a Board member’s question from earlier in the meeting.

Dr. Leah Rosenheck (LR Risk Consulting, Inc.), the study director, addressed the 

comment from Dr. Popendorf regarding the orientation of workers with respect to the air flow. 

As suggested by the HSRB, the researchers did measure air flow within the two test rooms, and 

those measurements are contained within the report. The average air flow exchange ranged from 

8 to 10 air exchanges per hour in room one and 7 air exchanges per hour in room two. A 

schematic on page 153 of the report shows the air flow and air vents with respect to the 

orientation of the workers. Dr. Rosenheck acknowledged that more detail regarding the workers’ 

orientation could have been added to the report. She referred the Board members to photographs 

on page 156 of the report, which depicted the containers of chemicals that were placed on the 

ground or countertops. The pictures show that the workers were perpendicular to the air flow, 

facing the wall, when the containers were on the countertop. There was some movement of the 

workers, especially if they had to lift a container and then swivel to face the bucket to pour. 

Thus, the air flow was perpendicular, with the exception of the 5 gallon buckets because of the 

direction of the basins. In those MEs, the workers were parallel to the direction of the air flow. 

Dr. Rosenheck elaborated on the question regarding the sequence of chemicals and water 

added to the spray bottles. Everyone added the chemical first and then the water. One person 

started by adding product to the bottle first, but had difficulty in stopping the water added to the 
20

spray bottle before it overflowed. This subject then tried to add water to the spray bottle first but 

only did this once because he or she did not know how much water to add to leave room for the 

chemical product at the top. As this was inefficient, the subject reverted to adding the product 

first. 

Dr. Manautou requested clarification from Dr. Rosenheck on the measurement cup that 

was used. He remarked that the measuring cup used in the first ME was not used in any

subsequent MEs and noted that this was a modification. Dr. Rosenheck responded that originally

the 8 oz measuring cup was to be used for Group 1 and the 16 oz cup for Group 2. The 8 oz 

measuring cup, however, did not have a spout. After the first ME, the researchers decided that all 

MEs should use the measuring cup with the spout. Dr. Manautou asked whether this resulted in a 

higher exposure for the first ME. Mr. Leighton answered that higher exposures were obtained 

within the study, so the data point was retained. 

Dr. Manautou asked whether the subjects, all of which were janitors with at least 1 year 

of experience, had received safety training in their jobs. Previous experience might be indicative 

of safer handling of chemicals. Dr. Rosenheck acknowledged that all of the subjects had previous 

janitorial or property maintenance experience, but the investigators did not ask whether they had 

safety training or other formal training. She added that many of the subjects possessed more than 

30 years of experience. 

Dr. Popendorf questioned the frequency of typical liquid disinfectant use in the study

population, as shown in Table 6 of the study report. Dr. Rosenheck responded that the 

participants were asked whether they pour liquid sanitizers as part of their job and how 

frequently, and most of the responses ranged from three times per week to daily.

Dr. Popendorf thanked Dr. Rosenheck for the diagram of the orientation of workers with 

respect to the air flow but deemed the volume of air exchanges per hour unhelpful. He asked 

whether information about the velocity of the air flow across the room existed. Dr. Rosenheck

explained that the air flow measurements were taken to calculate the air exchange. Dr. Popendorf 

remarked that air flow typically is relative to room volume. Dr. Parkin concurred that the values 

would be dependent on the volume of the room. Dr. Rosenheck agreed to investigate what raw 

data were available, noting that the air flow calculations were not included in the report.

Dr. Popendorf asked whether the facilities had been renovated or otherwise modified in the year 

since the study. If nothing has changed, it might be possible to go back and conduct the air 

velocity measurements. Dr. Rosenheck agreed to confirm whether any changes had been made to 

the facility.

Dr. Popendorf asked Dr. Rosenheck about the statement in the AEATF report that 

declared broadly that indoor exposure was higher than outdoor exposure. Dr. Rosenheck

commented that her experience with greenhouse studies indicated that indoor exposure tends to 

be higher. The PHED information appears to confirm that scenarios involving mixing and 

loading using a hand wand have higher dermal and inhalation exposure values for indoor than 

outdoor exposures. Dr. Rosenheck acknowledged that the statement would depend on the 

equipment in use and other factors, and Dr. Popendorf agreed.
21

Dr. Manautou asked where the water carboy was located relative to the dispensing 

containers. Dr. Rosenheck referred Dr. Manautou to page 157 of the report, which showed the 

spray bottles on the countertop near the containers. Dr. Manautou asked whether the distance 

remained consistent, and Dr. Rosenheck responded that the water carboys were used only with 

spray bottles and not in the other scenarios. 

Dr. Parkin solicited any further questions for the lead investigator, and none were offered.

She thanked Dr. Rosenheck for her answers. 

Charge to the Board – Science

Ms. Sherman read the science charge questions into the record:

 Was the research reported in the AEATF completed liquid pour study report (AEA05) 

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

AEATF?

 Has EPA adequately characterized, from a scientific perspective, the limitations on these 

data that should be considered when using the data in estimating the exposure of people 

who pour liquid antimicrobial pesticide products?

Board Science Review

Dr. Parkin asked Dr. Popendorf, as the lead discussant for the science review, to address the

science charge questions. Dr. Popendorf agreed with the first charge question and the Agency’s 

findings that the research reported in the AEATF completed liquid pour study was faithful to the 

design and objectives of the protocol and governing documents of the AEATF. 

In response to the second charge question, Dr. Popendorf agreed broadly given several 

limitations. He presented several clarifying comments and a few modifications. He reiterated his 

concern with the experience of the workers given the variations detailed in the documented 

observations. For example, eight out of 18 subjects changed their handling process during the ME to 

reduce the amount of dripping that occurred. Clearly, prior experience is not a factor, but experience 

handling the product is a factor. These data parallel residential users more than Dr. Popendorf 

expected.

Another issue is that the handlers did not wipe the spills, and there was no time interval 

between each pouring event within the ME such that spills were not given time to dry. This suggests 

that the exposures were higher than expected for a typical use of once per day, which is the 

frequency reported by most of the subjects. Dr. Popendorf observed that the high exposure data is a 

positive finding. 

Dr. Popendorf continued, remarking that there was not much justification for the statement 

that indoor exposure would be higher than performing the same activity outdoors. The study did not 

measure or document the velocity of the air drift. Although the air flow was probably sideways, 

ventilation might have been a factor, but the data are not available. 
22

Dr. Popendorf restated EPA’s declared limitation that the small sample size by itself does 

not create statistical limitations except for pouring into spray bottles. Dr. Popendorf remarked that 

the lack of variability in AaiH might have caused the odd statistics, not the fact that it was just six 

subjects in the group. He expressed concern with the lack of variability of the six people in the 

bottle group, which varied only by 1.3 in AaiH. The other groups (CP and RS) varied by four- to 

seven-fold in AaiH.

Another point of discussion was the issue of concentration. The Agency justifies the use of 

unit exposure values to adjust for concentration, but in this case all of the concentrations were the 

same and the only variation was the volume used. The fact that the statistics were weak should not 

be taken as evidence of weakness of applicability of unit exposure to extrapolate values on the basis 

of concentrations, which is strong. There is an implicit assumption that the volume used times the 

rate of exposure while in use has to be similar because the volume is expected to correlate with 

exposure. If the rate of exposure changed, exposure could increase or decrease. Eight out of 18 

subjects changed their behavior, which is another strong case for why the data need not be expected 

to follow proportionality. Dr. Popendorf indicated that the study data provide good justification to 

reduce the concentration 10-fold, even 100-fold, to try to get better power and achieve 

proportionality solely with hand exposure. 

Dr. Popendorf also remarked on the difference in the relatively low aerosol generation 

between the CP and RS scenarios. The T-test showed a difference with a 0.01 significance level. 

There are good reasons to pour from containers that have engineering controls. The respiratory

volume per minute rate used by the EPA in the science review was 1 cubic meter per hour (m3/hr), 

but several guidance documents should be considered, including the Occupational and Residential 

Exposure Test Guidelines, which suggest a different value of 1.33 m

3

/hr.

Dr. Parkin asked Dr. Popendorf for his official response to the second science charge 

question, to which he replied that EPA had not adequately characterized, from a scientific 

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

estimating the exposure of people who pour liquid antimicrobial pesticide products, but they could 

do so in the future. 

Dr. Parkin asked Dr. Young, the associate discussant for the science review, to present her 

comments. Dr. Young declared that the answer to the first question was “yes,” and the answer to the 

second question was “not yet,” but more could be done. She explained her comments from a

statistical point of view. First, the method of imputation used for the multiple imputation is incorrect 

because there might be reasons explaining the big changes in numbers. The problem lies with the 

initial estimate parameters used to generate the imputation values. Estimate parameters will change, 

which means that the imputed values are no longer correct for the estimated parameters. It is 

important to conduct this iterative process until the estimates do not vary. If multiple imputation is 

to be performed, it needs to be an iterative process so the imputed effects are consistent with the 

parameters. A five-fold imputation is the standard approach to capture variation. Means do not vary

as much as individual values; imputing five values would take advantage of the variation in the five 

values rather than imputing the average. Bayesian analysis is not required; there is a SAS procedure 

to perform multiple imputation analysis.
23

Dr. Young reiterated Dr. Johnson’s remark questioning the value of the arithmetic mean. 

The problem is illustrated on page 36 of Appendix A, which shows the constant as the arithmetic 

mean of the exponentiation of the intercept times the exponentiation of the error term. That becomes 

a constant, however, only if the AaiH does not vary and the slope is 1. The equation is invalid and 

the arithmetic mean of exposure is incorrect, as all three of the HSRB statisticians agreed. When 

exposure is considered, the intercept is a constant but the pounds of active ingredient and the error 

term depends on the observation, which cannot be separated. This equation could be improved with 

a Taylor series expansion, but that has its own problems. The error term being used is a mixed 

model with two variance components—one for the worker and one for the air environment—which 

cannot be combined. All of this is predicated on the fact that the geometric mean falls out naturally

but EPA wants an arithmetic mean. Dr. Young opined that there is no great value in calculating the 

arithmetic mean; calculating confidence intervals on the geometric mean would be more valuable.

Dr. Young also questioned the Q-Q plots. The assumption is a constant mean between the 

three groups (bottle, CP and RS). Given that the mean is different for each group, the researchers 

should use the residuals and not the observed values for each container type in the Q-Q plots to 

assess how the results could be improved. The residual of the model and the worker need to be 

separated to be evaluated appropriately in the Q-Q plot. 

Dr. Young also expressed concern with the variance among the groups, which were not the 

same. She did not see the model account for the differences in variance within the SAS code. The 

study does not have a random sample. It would be useful to consider the inequality in the variances 

within the model before discarding that variable. The differences in the groups, variance, and 

repeated measures for the same worker must be accounted for because it is not a simple random 

sample.

Dr. Young remarked that the slope of the equation causes issues. The Board needs to decide 

how they will react if they receive results indicating a slope greater than 1. If the estimated slope is 

between 0 and 1, the HSRB can argue that it is protective of human health, but this argument is not 

valid for values greater than 1. Negative estimated slopes do not make any sense. Slopes of zero 

also are not realistic, but EPA either must entertain the fact that the slope is 0 or separate the hands 

into a discrete analysis, which might show a slope of 1. 

Dr. Young declared that great progress had been made, but the present analysis contains 

severe, but fixable, limitations to the data as analyzed.

Dr. Parkin expressed appreciation to Dr. Young for her analysis and offered Dr. Manautou, 

the other associate discussant, an opportunity to speak. Dr. Manautou agreed with the points of 

clarification identified and expressed interest in a more detailed explanation for how the third 

exposure group was generated in terms of a statistical justification. In particular, he questioned how 

two factors are related statistically when they are interconnected. Mr. Leighton referred 

Dr. Manautou to Table 8 (in Appendix A of the EPA Science Review) for a more thorough 

statistical review and an explanation as to what provides more justification when deciding to 

separate the groups, the statistics or the logic. He emphasized that the logic would need to exist to 

justify separating the groups. Dr. Manautou requested clarification for the over- versus 

underestimation of exposure. Mr. Leighton responded that the two scenarios were first evaluated as 
24

designed and the combined exposures were higher than the CP (10 mg/lb) but lower than the bottle 

values (299 mg/lb). He emphasized that EPA had looked at the two scenarios of the study as 

designed before deciding to separate the bottle events.

Dr. Parkin requested any additional discussion by Board members. Dr. Kissel noted that the 

thresholds for under- and overestimation occur for two-thirds of the scenarios (CP and RS) at 

approximately 1,000 oz of product and at 30 oz for the bottle. Application of that volume of product 

to achieve the threshold of active ingredient exceeds what would be expected for 1 day of domestic 

use. He asked whether EPA, as it moved forward and used these data in models for domestic 

exposure, planned to acknowledge that these data might lead to an underestimation of exposure. 

Mr. Leighton remarked that EPA looks at the requirements of the label, such as the percentage of 

active ingredient. If the values were underestimated, more data would need to be collected. He 

clarified that domestic use was equivalent to consumer or nonoccupational use. 

Dr. Jordan explained that products sold for disinfectant use with trigger spray pumps were 

marketed differently, not labeled differently. When assessing the risk of the product, researchers 

would assess exposures associated with the assumption that the product would be used repeatedly

by the same person in multiple locations (e.g., multiple bathrooms in a hotel). Mr. Leighton 

remarked that one should look at the high end for exposure to a product. Problems occur if the 

values fall below the threshold. Dr. Kissel remarked that standard operating procedures (SOP) must 

be written very carefully because a potential misinterpretation of the label could lead to misuse of 

the product.

Dr. Kissel elaborated that the question relevant to the indoor and outdoor exposure issue 

involved aerosolization. One psychological factor that might affect exposure is that workers might 

be more careful and more inclined to clean spills that happen inside. If the worker is pouring a 

liquid outside, they might be less careful and might end up with product on their pant legs, for 

example. Thus, the indoor versus outdoor exposure argument extends beyond aerosols, and 

behavior should be considered in deciding whether indoor or outdoor exposures would be 

equivalent. 

Dr. Kissel agreed with the proposition that hand exposures should not be combined with the 

other dermal exposures, given the disparity in values between hand and other dermal exposures. The 

dermal exposures might comprise a fixed fractional absorption that is unrelated to the loading. 

Dr. Kissel remarked that bad science is unethical. The exposure load on the hands might be so high 

that uptake is inefficient, and people wash their hands more frequently. If product ends up on the 

pant leg, the exposure load will be low but it might be absorbed efficiently. Dr. Kissel expressed 

support for investigating the exposure to hands separately from the rest of the body given the logic 

of the situation.

Dr. Popendorf offered a consensus response. In response to the first charge question, all 

answers have been “yes.” In response to the second charge question, the answer is “yes,” with some 

qualifications.
25

Dr. Parkin asked the Board members if anyone dissented to the affirmative answer to 

question one, and no one did. There also was no dissent for the second question being answered 

“yes, but.”

Charge to the Board – Ethics

Ms. Sherman read the ethics charge question into the record:

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

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

Board Ethics Review

Dr. Parkin asked lead discussant Dr. Virginia Ashby Sharpe to comment on the ethics 

review. Dr. Sharpe expressed appreciation to the lead investigator for being so responsive to the 

Board’s comments during the proposal review and making the completed proposal review so easy. 

She also thanked Ms. Sherman for her ethics review, which included a decisive and detailed 

evaluation of the proposal and results. Dr. Sharpe presented her and Dr. Halanych’s conclusions, 

which indicated that the available information supports a determination that the study was 

conducted in substantial compliance with subparts K and L of 40 CFR part 26. Dr. Halanych

verbally confirmed Dr. Sharpe’s conclusions. 

Dr. Parkin solicited any ethical issues or concerns from the Board members. There being 

none, she asked Dr. Sharpe to repeat the specific response to the charge question. Dr. Sharpe replied 

that the available information supports a determination that the study was conducted in substantial 

compliance with subparts K and L of 40 CFR part 26. Dr. Parkin asked the Board members whether 

there was any dissent with regard to the ethics charge question or any remaining key issues to 

discuss. As none of the Board members disagreed with the charge question responses, Dr. Parkin 

remarked that the HSRB had completed its responses to the charge questions. 

An Update from the Work Group on the Return of Individual Research Results

Dr. Parkin acknowledged that the HSRB had convened a work group to investigate the 

return of research results to participants in third-party studies. The work group, which consists of 

HSRB members as well as external experts, met for a full day of deliberations on January 16, 2013. 

The work group is expected to report to the HSRB in 2013 for a public debate after securing a 

committee-wide agreement on how best to proceed with the return of individual research results, 

which is a topic that arose during several HSRB discussions in recent years.
26

Adjournment

Dr. Parkin expressed appreciation to the Board members for their diligent work during this 

review. Mr. Downing thanked the Board members for their productive discussion. He explained that 

the next HSRB meeting is scheduled for April 8 to 12, 2013. A notice of the exact dates and times 

will be issued in the Federal Register and on the HSRB website. Mr. Downing adjourned the 

meeting at 4:33 p.m.

Respectfully submitted:

Jim Downing

Designated Federal Officer

Human Studies Review Board

United States Environmental Protection Agency

Certified as accurate:

Rebecca T. Parkin, Ph.D., M.P.H.

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.
27

Attachments

Attachment A EPA HSRB Members

Attachment B Federal Register Notice Announcing Meeting

Attachment C Public Meeting Agenda
28

Attachment A

EPA HUMAN STUDIES REVIEW BOARD MEMBERS

Chair

+Rebecca Tyrrell Parkin, Ph.D., M.P.H. Term: 10/1/07-8/31/2013

Professorial Lecturer (EOH)

School of Public Health and Health Services

The George Washington University

Lake Frederick, VA

Vice Chair

+Jewell H. Halanych, M.D. Term: 11/14/11-8/31/2014

Assistant Professor

Department of Medicine

Division of Preventative Medicine

University of Alabama at Birmingham

Birmingham, AL

Members

+George C.J. Fernandez, Ph.D. Term: 5/1/2010-8/31/2013

Statistical Training Specialist 

SAS Institute, Statistical Training and Technical Services

Sparks, NV

+Sidney Green, Jr., Ph.D., Fellow, ATS Term: 10/19/2009-8/31/2015

Department of Pharmacology

Howard University College of Medicine (Retired)

Silver Spring, MD

+Elizabeth Heitman, Ph.D. Term: 9/1/2012-8/31/2015

Associate Professor of Medical Bioethics

Center for Biomedical Bioethics and Society

Vanderbilt University Medical Center

Nashville, TN 

+Dallas E. Johnson, Ph.D. Term: 8/31/2007-8/31/2013

Professor Emeritus 

Department of Statistics

Kansas State University

Manhattan, KS 
29

+John C. Kissel, Ph.D. Term: 9/1/2012-8/31/2015

Department of Environmental

and Occupational Health Sciences

School of Public Health

University of Washington

Seattle, WA 

+José E. Manautou, Ph.D. Term: 5/1/2010-8/31/2013

Associate Professor of Toxicology

Department of Pharmaceutical Sciences

School of Pharmacy

University of Connecticut

Storrs, CT 

+William J. Popendorf, Ph.D. Term: 10/19/2009-8/31/2015

Professor Emeritus

Department of Biology

Utah State University

Logan, UT

^Nu-May Ruby Reed, Ph.D., D.A.B.T. (1992-2012) Term: 9/1/2012-8/31/2015

Retired Staff Toxicologist 

California Environmental Protection Agency (Cal/EPA)

Department of Pesticide Regulation

Davis, CA

+Leonard Ritter, Ph.D., ATS Term: 11/14/2011-8/31/2014

Professor Emeritus (Toxicology)

School of Environmental Sciences

University of Guelph

Guelph, ON, Canada

+Virginia Ashby Sharpe, Ph.D. Term: 5/1/2010-8/31/2013

National Center for Bioethics in Health Care

Veterans Health Administration

Department of Veterans Affairs 

Washington, DC 20420

Bernard A. Schwetz, D.V.M., Ph.D. Term: 11/14/2011-8/31/2014

Retired Director

Office of Human Research Protections

Department of Health and Human Services

Cadott, WI
30

+Linda J. Young, Ph.D. Term: 3/28/2008-8/31/2014

Professor and Associate Chair

Department of Statistics

Institute of Food and Agricultural Sciences

University of Florida

Gainesville, FL 

+Present on January 17, 2013

^Present via telephone January 17, 2013
31

Attachment B

Federal Register Notice Announcing Meeting

[Federal Register Volume 77, Number 239 (Wednesday, December 12, 2012)] 

[Notices]

[Pages 74004 -74006]

From the Federal Register Online via the Government Printing Office [www.gpo.gov]

[FR Doc No: 2012-29983]

---------------------------------------------------------------------------------------------------------------------

ENVIRONMENTAL PROTECTION AGENCY

[EPA-HQ-ORD-2012-0892; FRL-9761-4]

Human Studies Review Board (HSRB); Notification of a Public Meeting

AGENCY: U.S. Environmental Protection Agency (EPA).

ACTION: Notice.

---------------------------------------------------------------------------------------------------------------------

SUMMARY: The EPA Office of the Science Advisor announces a public meeting of the Human 

Studies Review Board to advise the Agency on the EPA scientific and ethical reviews of research 

with human subjects

DATES: This public meeting will be held on January 17, 2013, from approximately 1:00 p.m. to 

approximately 4:30 p.m. Eastern Time. Comments may be submitted on or before noon (Eastern 

Time) on Thursday, January 10, 2013 

ADDRESSES: Submit your written comments, identified by Docket ID No. EPA-HQ-ORD2012-0982, by one of the following methods:

Internet: http://www.regulations.gov: Follow the on-line instructions for submitting comments.

E-mail: ORD.Docket@epa.gov.

Mail: Environmental Protection Agency, EPA Docket Center (EPA/DC), ORD Docket, 

Mailcode: 28221T, 1200 Pennsylvania Avenue, NW, Washington, DC 20460. 

 Hand Delivery: The EPA/DC Public Reading Room is located in the EPA Headquarters Library, 

Room Number 3334 in the EPA West Building, located at 1301 Constitution Avenue, NW, 

Washington, DC 20460. The hours of operation are 8:30 a.m. to 4:30 p.m. Eastern Time, Monday

through Friday, excluding Federal holidays. Please call (202) 566-1744 or e-mail the ORD Docket 

at ord.docket@epa.gov for instructions. Updates to Public Reading Room access are available on 

the Web site (http://www.epa.gov/epahome/dockets.htm).

Instructions: Direct your comments to Docket ID No. EPA-HQ-ORD- 2012-0892. EPA’s 

policy is that all comments received will be included in the public docket without change and may

be made available online at http://www.regulations.gov, including any personal information 

provided, unless the comment includes information claimed to be Confidential Business 
32

Information (CBI) or other information the disclosure of which is restricted by statute. Do not 

submit information that you consider to be CBI or otherwise protected through 

http://www.regulations.gov or e-mail. The http://www.regulations.gov Web site is an “anonymous 

access” system, which means EPA will not know your identity or contact information unless you 

provide it in the body of your comment. If you send an e-mail comment directly to EPA without 

going through http://www.regulations.gov, your e-mail address will be automatically captured and 

included as part of the comment that is placed in the public docket and made available on the 

Internet. If you submit an electronic comment, EPA recommends that you include your name and 

other contact information in the body of your comment and with any electronic storage media you 

submit. If EPA cannot read your comment due to technical difficulties and cannot contact you for 

clarification, EPA may not be able to consider your comment. Electronic files should avoid the use 

of special characters, any form of encryption, and be free of any defects or viruses.

FOR FURTHER INFORMATION CONTACT: Any member of the public who wishes to 

receive further information should contact Jim Downing at telephone number: (202) 564-2468; fax: 

(202) 564-2070; e-mail address: downing.jim@epa.gov, or Lu-Ann Kleibacker at telephone 

number: (202) 564-7189; fax: 202-564-2070; e-mail address: kleibacker.lu-ann@epa.gov; mailing 

address: Environmental Protection Agency, Office of the Science Advisor (8105R), 1200 

Pennsylvania Avenue, NW, Washington, DC 20460. General information concerning the EPA 

HSRB can be found on the EPA Web site at http://www.epa.gov/osa/hsrb/.

SUPPLEMENTARY INFORMATION:

Location: The meeting will be held at the Environmental Protection Agency, Conference 

Center—Lobby Level, One Potomac Yard (South Building.) 2777 S. Crystal Drive, Arlington, VA 

22202. 

Meeting access: Seating at the meeting will be on a first-come basis. To request 

accommodation of a disability, please contact the persons listed under FOR FURTHER 

INFORMATION CONTACT at least ten business days prior to the meeting using the 

information under FOR FURTHER INFORMATION CONTACT, so that appropriate 

arrangements can be made.

Procedures for providing public input: Interested members of the public may submit relevant 

written or oral comments for the HSRB to consider during the advisory process. Additional 

information concerning submission of relevant written or oral comments is provided in Section I, 

“Public Meeting,” under subsection D. “How May I Participate in this Meeting?'” of this notice.

I. Public Meeting

A. Does this action apply to me?

 This action is directed to the public in general. This action may, however, be of particular 

interest to persons who conduct or assess human studies, especially studies on substances regulated 

by EPA, or to persons who are, or may be required to conduct testing of chemical substances under 

the Federal Food, Drug, and Cosmetic Act (FFDCA) 

[[Page 74005]]

or the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). This notice might also be of 

special interest to participants of studies involving human subjects, or representatives of study
33

participants or experts on community engagement. Since many entities may also be interested, the 

Agency has not attempted to describe all the specific entities that may be affected by this action. If 

you have any questions regarding the applicability of this action to a particular entity, consult Jim 

Downing or Lu-Ann Kleibacker listed under FOR FURTHER INFORMATION CONTACT.

B. How can I access electronic copies of this document and other related information?

 In addition to using regulations.gov, you may access this Federal Register document 

electronically through the EPA Internet under the “Federal Register” listings at 

http://www.epa.gov/fedrgstr/.

 Docket: All documents in the docket are listed in the http://www.regulations.gov index. 

Although listed in the index, some information is not publicly available, e.g., CBI or other 

information whose disclosure is restricted by statute. Certain other material, such as copyrighted 

material, will be publicly available only in hard copy. Publicly available docket materials are 

available either electronically in http://www.regulations.gov or in hard copy at the ORD Docket, 

EPA/ DC, Public Reading Room. The EPA/DC Public Reading Room is located in the EPA 

Headquarters Library, Room Number 3334 in the EPA West Building, located at 1301 Constitution 

Avenue, NW, Washington, DC 20460. The hours of operation are 8:30 am to 4:30 p.m. Eastern 

Time, Monday through Friday, excluding Federal holidays. Please call (202) 566-1744 or email the 

ORD Docket at ord.docket@epa.gov for instructions. Updates to Public Reading Room access are 

available on the Web site (http://www.epa.gov/epahome/dockets.htm). 

 EPA’s position paper(s), charge/questions to the HSRB, and the meeting agenda will be 

available by the first of January 2012. In addition, the Agency may provide additional background 

documents as the materials become available. You may obtain electronic copies of these 

documents, and certain other related documents that might be available electronically, from the 

regulations.gov Web site and the EPA HSRB Web site at http://www.epa.gov/osa/hsrb/. For 

questions on document availability, or if you do not have access to the Internet, consult either Jim 

Downing or Lu-Ann Kleibacker listed under FOR FURTHER INFORMATION CONTACT.

C. What should I consider as I prepare my comments for EPA?

 You may find the following suggestions helpful for preparing your comments:

 1. Explain your views as clearly as possible. 

 2. Describe any assumptions that you used.

 3. Provide copies of any technical information and/or data that you used to support your views.

 4. Provide specific examples to illustrate your concerns and suggest alternatives. 

 5. To ensure proper receipt by EPA, be sure to identify the docket ID number assigned to this 

action in the subject line on the first page of your response. You may also provide the name, date, 

and Federal Register citation.

D. How may I participate in this meeting?

 You may participate in this meeting by following the instructions in this section. To ensure 

proper receipt by EPA, it is imperative that you identify docket ID number EPA-HQ-ORD-2011-

0954 in the subject line on the first page of your request. 

 1. Oral comments. Requests to present oral comments will be accepted up to Thursday, January

19, 2012. To the extent that time permits, interested persons who have not pre-registered may be 

permitted by the Chair of the HSRB to present oral comments at the meeting. Each individual or 

group wishing to make brief oral comments to the HSRB is strongly advised to submit their 
34

request (preferably via e-mail) to Jim Downing or Lu-Ann Kleibacker, under FOR FURTHER 

INFORMATION CONTACT, no later than noon, Eastern Time, Thursday, January 19, 2012, in 

order to be included on the meeting agenda and to provide sufficient time for the HSRB Chair and 

HSRB Designated Federal Official (DFO) to review the meeting agenda to provide an appropriate 

public comment period. The request should identify the name of the individual making the 

presentation and the organization (if any) the individual will represent. Oral comments before the 

HSRB are generally limited to five minutes per individual or organization. Please note that this 

includes all individuals appearing either as part of, or on behalf of, an organization. While it is our 

intent to hear a full range of oral comments on the science and ethics issues under discussion, it is 

not our intent to permit organizations to expand the time limitations by having numerous 

individuals sign up separately to speak on their behalf. If additional time is available, further public 

comments may be possible.

 2. Written comments. Submit your written comments prior to the meeting. For the HSRB to 

have the best opportunity to review and consider your comments as it deliberates on its report, you 

should submit your comments at least five business days prior to the beginning of this meeting. If 

you submit comments after this date, those comments will be provided to the Board members, but 

you should recognize that the Board members may not have adequate time to consider those 

comments prior to making a decision. Thus, if you plan to submit written comments, the Agency

strongly encourages you to submit such comments no later than noon, Eastern Time, Thursday, 

January 19, 2012. You should submit your comments using the instructions in Section I., under 

subsection C., “What should I consider as I prepare my comments for EPA?” In addition, the 

Agency also requests that persons submitting comments directly to the docket also provide a copy

of their comments to Jim Downing or Lu-Ann Kleibacker listed under FOR FURTHER 

INFORMATION CONTACT. There is no limit on the length of written comments for 

consideration by the HSRB.

E. Background

 The HSRB is a Federal advisory committee operating in accordance with the Federal Advisory

Committee Act (FACA) 5 U.S.C. App.2 Sec.9. The HSRB provides advice, information, and 

recommendations to EPA on issues related to scientific and ethical aspects of human subjects 

research. The major objectives of the HSRB are to provide advice and recommendations on: (1) 

Research proposals and protocols; (2) reports of completed research with human subjects; and (3) 

how to strengthen EPA’s programs for protection of human subjects of research. The HSRB 

reports to the EPA Administrator through EPA’s Science Advisor. 

 1. Topics for discussion. At its meeting on January 17, 2013, EPA’s Human Studies Review 

Board will consider scientific and ethical issues surrounding these topics:

 a. A completed study report from the Antimicrobial Exposure Assessment Task Force II 

(AEATF) in which the dermal and inhalation exposure of professional janitorial workers was 

[[Page 74006]]

monitored as they poured liquid antimicrobial pesticide products from conventional or reducedsplash containers into different sizes and types of source containers. EPA seeks the advice of the 

HSRB on the scientific soundness of this completed research and on its appropriateness for use in 

estimating exposure that results from pouring liquid antimicrobial pesticide products. EPA also 

seeks the advice of the HSRB on whether available information supports a determination that the 

study was conducted in substantial compliance with subparts K and L of 40 CFR Part 26.
35

 2. Meeting minutes and reports. Minutes of the meeting, summarizing the matters discussed and 

recommendations, if any, made by the advisory committee regarding such matters, will be released 

within 90 calendar days of the meeting. Such minutes will be available at 

http://www.epa.gov/osa/hsrb/ and http://www.regulations.gov. In addition, information regarding 

the Board’s Final meeting report, will be found at http://www.epa.gov/osa/hsrb/ or from the person 

listed under FOR FURTHER INFORMATION CONTACT.

 Dated: December 3, 2012. 

Glenn Paulson

EPA Science Advisor

[FR Doc. 2012-29983 Filed 12-11-12; 8:45 am] 

BILLING CODE 6560-50-P
36

Attachment C

U.S. ENVIRONMENTAL PROTECTION AGENCY (EPA)

HUMAN STUDIES REVIEW BOARD (HSRB)

JANUARY 2013 PUBLIC MEETING AGENDA

Environmental Protection Agency Conference Center

Lobby Level - One Potomac Yard (South Bldg.) 

2777 S. Crystal Drive, Arlington, VA 22202 

Thursday, January 17, 2013

HSRB WEB SITE http://www.epa.gov/osa/hsrb/

Docket Telephone: (202) 566 1752

Docket Number: EPA–HQ–ORD–2012–0892

1:00 PM* Convene Public Meeting – Mr. Jim Downing, Designated Federal Officer, EPA 

HSRB, Office of the Science Advisor (OSA)

Introduction of Board Members – Dr. Rebecca Parkin, Ph.D., MPH, HSRB Chair

Welcome – Dr. Glenn Paulson, Ph.D., Science Advisor, EPA

Opening Remarks – Dr. Steven Bradbury, Ph.D., Director, Office of Pesticide 

Programs (OPP), Office of Chemical Safety and Pollution Prevention (OCSPP), 

EPA

Follow-Up on Previous HSRB Recommendations – Mr. William Jordan, OPP, 

OCSPP, EPA

Session 1: A completed study report from the Antimicrobial Exposure Assessment Task 

Force II (AEATF) in which the dermal and inhalation exposure of professional 

janitorial workers was monitored as they poured liquid antimicrobial pesticide 

products from conventional or reduced-splash containers into different sizes 

and types of receiving containers. EPA seeks the advice of the HSRB on the 

scientific soundness of this completed research and on its appropriateness for use in 

estimating exposure that results from pouring liquid antimicrobial pesticide 

products. EPA also seeks the advice of the HSRB on whether available information 

supports a determination that the study was conducted in substantial compliance 

with subparts K and L of 40 CFR Part 26.

1:40 PM EPA Science Review – Mr. Tim Leighton (OPP, EPA), Dr. Jonathan Cohen, Ph.D. 

(ICF International)

2:15 PM Board Questions of Clarification – Dr. Rebecca Parkin, Ph.D., MPH (HSRB 

Chair), EPA, Principal Investigator/Sponsor

2:45 PM EPA Ethics Assessment – Ms. Kelly Sherman (OPP, EPA)

3:15 PM Board Questions of Clarification – Dr. Rebecca Parkin, Ph.D., MPH (HSRB 

Chair), EPA, Principal Investigator/Sponsor

3:45 PM Break

3:55 PM Public Comments 
37

4:05 PM Board Discussion 

Charge to the Board – Science:

 Was the research reported in the Antimicrobial Exposure Assessment Task Force II

(AEATF) completed liquid pour study report (AEA05) faithful to the design and 

objectives of the protocol and governing documents of AEATF?

 Has EPA adequately characterized, from a scientific perspective, the limitations on these 

data that should be considered when using the data in estimating the exposure of people 

who pour liquid antimicrobial pesticide products?

Charge to the Board – Ethics:

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

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

5:00 PM* Adjournment

*Agenda times are approximate and subject to change depending upon the discussion.