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Minutes of the

United States Environmental Protection Agency (EPA) 

Human Studies Review Board (HSRB)

January 26, 2011 Public Meeting

Docket Number: EPA-HQ-ORD-2010-0970

HSRB Web Site: http://www.epa.gov/osa/hsrb

Committee Members:(See EPA HSRB Members list – Attachment A) 

Date and Time: Wednesday, January 26, 2011, 9:15 AM – 5:30 PM

(See Federal Register Notices – Attachment B) 

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

VA 22202

Purpose: The EPA Human Studies Review Board provides advice, information, and 

recommendations on issues related to the scientific and ethical aspects of 

human subjects research. 

Attendees: Chair: Sean Philpott, Ph.D., M.S. Bioethics

Vice Chair: Janice Chambers, Ph.D., D.A.B.T.

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

Vanessa Northington Gamble, M.D., Ph.D.

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

Dallas E. Johnson, Ph.D.

Michael D. Lebowitz, Ph.D., FCCP

José E. Manautou, Ph.D.

Jerry A. Menikoff, M.D. 

William J. Popendorf, Ph.D.

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 

in these minutes. 

Meeting Administrative Procedures

Mr. Jim Downing (Designated Federal Officer [DFO], Human Studies Review Board 

[HSRB or Board], Office of the Science Advisor [OSA], U.S. Environmental Protection Agency 

[EPA or Agency]) convened the meeting and welcomed Board members, EPA colleagues, and 

members of the public. He thanked Board members for their work in preparing for the 

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

Act (FACA), he serves as liaison between the Board and EPA and is responsible for ensuring that 

all FACA requirements are met. The DFO must 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 the OSA and the Office of the General Counsel, 

Mr. Downing has reviewed the reports to ensure that all ethics requirements are met. 

He informed members that there were two challenging discussion items on the agenda for 

the meeting, and that agenda times are approximate. Copies of the meeting materials and public 

comments will be available on www.regulations.gov under docket number EPA-HQ-ORD-2010-

0970. Following the presentations, time has been scheduled for questions of clarification to EPA 

staff and the principal investigator and sponsors of the studies discussed. A public comment 

period will be maintained and remarks must be limited to 5 minutes. During Board discussions, 

if members require clarification from the public, they may request such information through the 

Chair or DFO. All background materials for the meeting will be available in the public docket 

and most also are available on the HSRB Web site. 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 as a 

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

materials presented. EPA will announce the Board review and subsequent approval of the report 

through the Federal Register. Mr. Downing welcomed Dr. Warren Lux (Director of the Program 

in Human Research Ethics, OSA, EPA) who would offer the Board welcoming remarks. 

Welcoming Remarks

Dr. Lux welcomed all in attendance on behalf of EPA’s Program in Human Research 

Ethics and Dr. Paul Anastas, EPA Science Advisor, and expressed his appreciation that the HSRB 

was among the program’s components. He noted that the Board’s expertise and thoroughness had 

been critical to the program’s success, and that its members had contributed significantly to the 

scientific and ethical standards adopted by the regulated community. He thanked his colleagues 

in EPA’s Office of Pesticide Programs (OPP) for their preparation and commitment to HSRB 

activities, and the regulated community and the public for their engagement with the Board. He 

wished the Board a successful and productive meeting, and turned the meeting over to Dr. Sean 

Philpott, HSRB Chair. 

Introduction and Identification of Board Members

Dr. Sean Philpott welcomed members of the public to the meeting and thanked the 

Agency and Board members for their service. He asked Board members to introduce themselves 

and welcomed Mr. William Jordan (OPP, EPA). 

EPA Follow-up on Previous HSRB Recommendations

Mr. Jordan added his welcome and thanks. He noted that at the previous HSRB meeting 

in October 2010, the Board examined the first major completed study on human exposure for 
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people handling pesticides, Antimicrobial Exposure Assessment Task Force II (AEATF–II) 

Report AEA03, Dermal and Inhalation Monitoring of Workers Mopping Floors with an 

Antimicrobial Product. 

The HSRB offered recommendations regarding the statistical analyses performed, and Dr. 

Jonathan Cohen, a consultant to EPA, performed additional statistical analyses that confirmed 

and supported the conclusions reached by EPA. Based on the additional analysis and the Board’s 

recommendations, EPA intends to use the data from the study to assess future applications for 

antimicrobial products that involve application through mopping; none are pending at this time.

Protocol reviews conducted at the October 2010 HSRB meeting included that of the No 

Mas 003 Field Efficacy Test of Para-menthane-3,8-diol (PMD) and Lemongrass Oil-Based 

Repellent Against Mosquitoes. The Board offered comments regarding the statistical analysis of 

the data set that would be generated by the study, and the study director, Dr. Scott Carroll of 

Carroll-Loye Biological Research, has proposed a Weibull distribution for analysis of the data. 

The other two protocol reviews conducted in October 2010 were both from the 

Agricultural Handler Exposure Task Force (AHETF): AHE-400, New Scenario Design and 

Protocol for Applicators Using Backpack Sprayers or Handgun Sprayers for Rights of Way, and 

AHE-120, Revised Scenario Design and Protocol for Exposure Monitoring of Workers during 

Mixing and Loading of Pesticide Products in Water Soluble Packets. The Board found both 

protocols to be scientifically and ethically acceptable. The AHETF has made revisions and 

submitted protocols to Independent Institutional Review Board, Inc. (IIRB), which approved 

them. The recruiting process for AHE-400 will begin on February 1, 2011, and recruitment for 

AHE-120 is scheduled to begin in March 2011. The studies are expected to be completed this 

summer, and the Board will likely review the results in October 2011 or January 2012. 

Mr. Jordan also informed the Board that EPA Administrator Lisa Jackson signed a 

Federal Register notice of proposed rulemaking on January 18, 2011, for the proposed revisions 

to EPA’s ―Rule on Protections for Subjects in Human Research Involving Pesticides.‖ It will be 

published in early February 2011, and will include a 60-day public comment period. The content 

of the proposed amendments matches what has previously been described to the Board. The 

proposed changes serve primarily to codify practices that EPA has been following in its reviews, 

and ensure that the research performed under this rule meets high ethical standards and is 

scientifically sound. Mr. Jordan does not expect the proposed rule to generate much controversy. 

Session 1: AHETF Report of a Completed Scenario Monograph and Study Reports of Five 

Field Studies Measuring the Dermal and Inhalation Exposure of Workers Applying Liquid 

Spray Pesticides to Tree or Trellis Crops Using Closed Cab Airblast Equipment

Background

Ms. Kelly Sherman (OPP, EPA) noted that the closed cab airblast applicator study is the 

first AHETF completed study and monograph to be reviewed by the HSRB. Questions for 

completed studies differ from those for protocols, and Ms. Sherman explained that the Board 
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should consider if: the proposal was appropriately amended after review by EPA and the HSRB; 

it was executed faithfully; results achieved objectives; and it was conducted ethically. 

The closed cab airblast applicator study involved five separate field studies in different 

locations with varying crops: AHE55, AHE56, AHE57, AHE58, and AHE59. The study 

monitored 24 subjects’ dermal and inhalation exposures during pesticide application with closed 

cab airblast equipment. The HSRB reviewed protocols for these studies in June and October 

2008. 

EPA Science Assessment

Mr. Matthew Crowley (OPP, EPA) thanked colleague Mr. Bayazid Sarkar (OPP, EPA) for 

his statistical analyses of the study data. The research objectives were to collect robust dermal 

and inhalation exposure data of workers applying liquid spray pesticides with closed cab airblast 

equipment for use in regulatory assessments of pesticides. This was a study designed to capture 

the variability of exposure encountered by agricultural workers. The primary objective was to 

determine the amount of dermal exposure, and the secondary objective was to determine whether 

the relationship between the amount of active ingredient handled (AaiH) and exposure was 

proportional or independent. The AHETF previously had demonstrated that a sample size of 25 

(5 x 5 configuration) could satisfy the objectives; because of logistical considerations as well as 

necessary scripting, however, true random sampling was not feasible. The AHETF targeted 

certain locations and worked with EPA to ensure that there was diversity among workers and 

different AaiH. The task force was responsive to HSRB comments on the study protocol. 

The AHETF was able to collect data from distinct geographical locations across the 

United States. Only one location per EPA growing region was monitored. Five subjects were 

monitored in each location except for one, in which four were monitored; this occurred because 

no monitor was available for the fifth worker. All subjects were male except for one female. 

Their work experience varied, as did the equipment, but all vehicles used had functioning 

windows and air conditioning. The goal was for the task force to configure each of the subjects 

within a study into one of five target ranges of AaiH. In most cases, this was successful. Dermal 

exposure was monitored by hand wash, face and neck wipe, and whole body dosimeter (WBD), 

and inhalation exposure was monitored by air pump and Occupational Safety and Health 

Administration Versatile Sampler (OVS) tubes. 

Several deviations from the protocol occurred, but in EPA’s opinion, none undermined or 

compromised the exposure results. In some cases, EPA suggested that the protocol be edited in 

the future to account for some of the deviations, such as with the requirement of 4 hours of spray 

time versus 4 hours of exposure monitoring time. The studies included Quality Assurance 

Statements, and the AHETF Quality Assurance Unit ensures that studies follow EPA Good 

Laboratory Practice Standards. Both negative controls (blanks) and positive controls (spikes) 

were included in the study. Some residues were detected in the field that should be discussed in 

the study reports. Exposure measurements represent workers wearing long-sleeved shirts, pants, 

chemical-resistant gloves, shoes/socks, and no respirator. All measurements were adjusted by 

average recovery of corresponding field fortification matrix and level. Left-censored data were 

present mainly in the face/neck wipes and OVS back sections results. Based on 
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recommendations from previous HSRB meetings, if the measured contribution from hands and 

face/neck represents between 20 percent and 60 percent of the total, measurements are to be 

adjusted upward by 2, or a validation study supporting the method’s efficiency must be provided. 

This is referred to as Method Efficiency Adjusted (MEA) or Method Efficiency Corrected 

(MEC) data. 

Dermal exposure ranged from 10 to 3,000 micrograms (μg). Inhalation exposure ranged 

from 0.1 to 67 μg. For inhalation, in one study, the worker was monitored, but the amount of 

time the air pump was operating was not recorded, so the sample size was 23. The AHETF 

characterized the estimates of exposures normalized by AaiH by empirical estimates, simple 

random sample, and mixed model method; the latter is the most appropriate for the study. Both 

the dermal and inhalation unit exposures (μg exposure per pound [lb] active ingredient [ai] 

handled) follow a log normal distribution. Statistical analysis demonstrates that the primary 

objective benchmark was met, and no additional monitoring is necessary. In terms of the 

secondary objective, in routine EPA assessments of handler exposure, exposure is predicted from 

AaiH, which assumes the two are proportional. The mixed model regression slope results show 

that this is the case for inhalation exposure, but show that dermal exposure is independent from 

AaiH. Therefore, the secondary benchmark was met for inhalation exposure but not dermal 

exposure. Considering the inconclusive results on dermal exposure, EPA performed additional 

analyses that found a stronger relationship between dermal exposure and handler entrances into 

and exits from the cab than AaiH. Field observations showed high exposures potentially caused 

by incidental contacts, such as brushing against foliage or touching with bear hands exterior 

surfaces that may have residue on them. Incidental contacts may correlate with the number of 

times a handler enters or exits the vehicle.

In conclusion, EPA agreed that the research design was acceptable despite its limitations. 

The selection of the workers was randomized to the extent possible. The data are recommended 

for use in regulatory assessments with AaiH normalization as a default condition; they should not 

be used, however, for assessments of high volatility chemicals.

EPA Ethics Assessment

Ms. Sherman explained that recruiting was conducted following a three-phase process 

that is outlined in the protocols, and in general the process in the standard operating procedures 

(SOPs) was followed. The initial recruitment list was generated from public lists and varied 

across the five studies from several hundred to several thousand. This list was narrowed using 

acreage size and other qualifying questions; the study director then spoke to those who were 

interested and could participate. There was one reported deviation in the Georgia pecan study. 

Because of a research delay caused by a tropical storm, several of the growers initially planning 

to participate in the study were either no longer available or willing to participate. Two referred 

growers ultimately became study subjects, but EPA determined that this did not compromise the 

recruiting process. 

Twenty-four subjects were monitored, including one female who was not pregnant. Most 

of the subjects preferred to conduct their consent process in English rather than Spanish, but 

there were three who chose Spanish, and one subject in Florida who self-identified as a non-
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reader used a witness for the consent process. There was diversity in age (20 to 70 years old) and 

level of experience (3 to 50 years). In two cases, the subjects reported a surprisingly large 

amount of experience in comparison to their ages, so those values may be questionable. All of 

the subjects except for one requested to have their exposure results provided to them at the end 

of the study. None of the subjects withdrew, and none were removed from participation by the 

task force. 

Exposure monitoring was conducted without incident, and no adverse events were 

reported. Initial protocols of all of the studies were reviewed by IIRB. Subsequent amendments 

and deviations were reviewed under expedited procedures. Eight amendments were approved by 

IIRB across the five studies, and 13 reported deviations were reviewed and acknowledged by 

IIRB. 

A large number of ethics issues were raised by the HSRB and EPA in terms of the study 

protocols, and in general, the researchers responded to all of the comments. Changes were 

implemented at different times: some before the first two studies were conducted, some before 

the next group of three studies, and some have been implemented for future protocols. 

Additionally, there were a number of protocol amendments; each of the five studies was 

amended at least once to address HSRB and EPA comments, and there were additional 

amendments to the three studies conducted in 2009 (AHE57, 58, 59). An amendment to study 

AHE59 involved the addition of two new carbaryl products to the protocol. When it became 

close to the time to conduct the monitoring, the AHETF learned that there were two eligible 

growers who wanted to use two products containing carbaryl that were not among those that had 

been approved previously. EPA approved of the amendment, and it also was approved by IIRB, 

but not through a formal protocol amendment. EPA did not consider this an ethics violation.

Key deviations reported across the five studies included, in study AHE56, a subject 

signing the informed consent form (ICF) after putting on the inner dosimeter. It was reported that 

he had given oral consent before donning the dosimeter, and he signed the ICF shortly after 

dressing. This was not in accordance with the protocol, but EPA did not consider it an ethics 

violation. 

There were 13 unreported deviations in the study report, including the fact that minimum 

spray time was not reached, and a subject contacted contaminated surfaces while not wearing 

gloves. In this case, he was not reminded to wear gloves by the monitor, and the study director 

was not informed. Observations were made of subjects exiting the cab while not wearing gloves 

in three of the studies. These deviations were compared to the Worker Protection Standard 

(WPS) that provides personal protective equipment (PPE) requirements for individuals working 

inside enclosed cabs. The WPS states that PPE required on the product label must be worn ―if it 

is necessary to exit the cab and contact pesticide-treated surfaces in the treated area.‖ In these 

cases, the surfaces contacted by workers not wearing gloves may have been contaminated but 

were not treated, and therefore, the deviation did not constitute a WPS violation. The protocol for 

the study, however, required a higher standard, and the failures to remind the worker to wear 

gloves and to report the deviation to the study director are violations of SOPs. In addition, these 

protocol and SOP deviations should have been reported promptly to IIRB. Ms. Sherman 
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determined that the deviations did not constitute an ethical violation because there was no intent 

to harm the subject, the safety of the subjects was not jeopardized, there was no violation of 

product labels or the WPS, and investigators were not sufficiently informed about what type of 

behavior should have required a warning. She also concluded that there was no regulatory 

violation because of these deviations. 

The study overall was complete and well-documented, and requirements of ethical 

documentation at 40 Code of Federal Regulations (CFR) §26.1303 were satisfied. Ms. Sherman’s 

findings were that the relevant substantive acceptance standards were met, and she concluded 

that available information indicates that the AHETF closed cab airblast applicator studies 

(AHE55, 56, 57, 58, 59) were conducted in substantial compliance with subparts K and L of 40 

CFR part 26.

Board Questions of Clarification

Dr. Michael Lebowitz asked why the California study was so different in terms of both 

exceedance of the upper limits of the strata, the design, and also the WBD field fortification 

samples. Mr. Crowley responded that the task force may have something to add about the 

California study; it is correct that it did have the most deviation from the targets. Variability in 

field fortification existed across all of the studies. Dr. Lebowitz noted that he had seen the data 

on wind speed, temperature, and humidity, but had not seen any analysis of the effect of any of 

those factors in the exposure assessments. Mr. Crowley replied that these analyses were not 

conducted, but EPA might be able to determine that information from the data. 

Dr. Linda Young stated that the assumption of normalization is that proportionality holds. 

What would be the consequences from the regulatory standpoint if that assumption is made and 

it is incorrect? Would it be protective of humans? Mr. Crowley answered that the slopes of the 

line were less than one. If the slope is assumed to be one, it would indicate that exposure is being 

overestimated. There is not a chance that the exposure would be underestimated.

Dr. Dallas Johnson commented that in the report and presentation, it was mentioned that 

80 percent power was used, and asked if there was always a 95 percent confidence interval (CI). 

Mr. Crowley confirmed that this was the case. 

Dr. William Popendorf noted that if proportionality is assumed but is not present, this 

would overprotect for high amounts of use but underprotect for low amounts of use. Mr. Crowley 

replied that the method applied in EPA’s assessments generally is to use maximum application 

rates, with amounts treated that would be considered at the high end of the range. He added, 

however, that Dr. Popendorf was correct in his assumption. 

Dr. Young stated that it was not quite clear how the assessment of 80 percent power was 

conducted. Mr. Crowley answered that he would defer to Mr. Sarkar on this issue, but that the 

AHETF’s governing document had a description stating that if the 95 percent CI slope had the 

width of 1.4, it would correspond to a power of 80 percent. Mr. Sarkar agreed that more detail 

was presented in the governing document, but a CI of 1.4 translates to 80 percent power. Dr. 

Philpott asked that the governing document containing the information be provided to Drs. 
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Young and Johnson, and then be addressed in the discussion if there are concerns. 

Dr. José Manautou noticed in the reports that with the data for both dermal and inhalation 

exposure (on slides 24 through 26), density of the foliage varies from one site to another. The 

Florida site is the most consistent. He asked if the Agency assessed whether the foliage density 

impacts the total outcome of inhalation or dermal exposure. If the foliage is less dense, perhaps 

more of the chemical will stay in the air and come into contact with the workers. Mr. Crowley 

commented that this was a good observation; EPA can look at the different variables and think 

about how they could affect exposure. Analysis on foliage density was not conducted, but could 

be to the extent that the data allow. The researchers did not target certain levels of density, so 

when EPA uses the data, numbers will be used without consideration of that as a specific 

variable. 

Dr. George Fernandez questioned why the 1.645 value was used for the upper CI 

computation. Mr. Crowley confirmed that Dr. Fernandez was asking about the calculation of the 

95th percentile. Dr. Fernandez responded that he was, but because the sample size was 24, he did 

not believe that 1.645 is the correct value to use. Mr. Crowley responded that perhaps the value 

should be different because the sample size is lower than what is standard for using that figure. 

He agreed that this was a good point and could be valuable in terms of a recommendation. Dr. 

Fernandez added that the study assumes that the slope is equal in the five crops rather than 

testing this assumption. Dr. Philpott suggested that this point be reintroduced during the Board’s 

discussion period. 

Dr. Janice Chambers asked why the two sections of the OVS tube were analyzed 

separately. Mr. Crowley answered that this was discussed among the regulatory agencies in terms 

of concerns about breakthrough going through the full sampler. 

Dr. Manautou noted the proportionality and independence between dermal exposure and 

AaiH, and mentioned that a relationship between dermal exposure and vehicle entrances and 

exits was found. He assumes that once the data from the open cab equipment are reviewed, it 

will address this issue. Mr. Crowley agreed that it would be useful. 

Dr. Vanessa Northington Gamble commented that the language of the federal government 

should be used in EPA’s reviews, and therefore not just ―ethnicity‖ but ―race and ethnicity‖ 

should be used. 

Dr. Virginia Ashby Sharpe noted, on page 28 of EPA’s report referencing the incidental 

exposures and failure of observer to intervene, that it states ―until now neither EPA nor HSRB 

has focused on the application of protocol SOPs to the kind of situations described in this 

report.‖ She questioned if this statement was referring to what type of activities or deviations 

should trigger an intervention. Ms. Sherman responded that the type of behavior that would 

cause the researcher to intervene was not a specific point of discussion. Occasionally, workers 

forget to put gloves on when exiting the cab. There could be value in this type of behavior from a 

science perspective in having those exposure points, but how far along a behavior that departs 

from SOPs should progress before being stopped by a researcher is unclear. Dr. Sharpe inquired, 

regarding the WPS advisor consult, given the terminology ―treated surface,‖ whether the worker 
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could put his/her hand directly into a tank containing pesticide and this would still be consistent 

with the WPS. Ms. Kathy Davis (OPP, EPA) replied that the WPS does not address that issue 

specifically, but if a worker was putting his/her hand in the tank to clean or conduct another 

activity in the handler description, PPE would be required. 

Dr. Johnson asked how a glove could be removed without contaminating the other hand. 

Ms. Davis responded that there was a technique to safely perform this act.

Dr. Philpott invited AHETF representative Dr. Victor Cañez (AHETF Technical Chair, 

BASF Corporation) to respond to Board questions of clarification. Dr. Lebowitz questioned what 

the difference was between the California study and the other studies in terms of the WBD field 

fortification samples and targets of AaiH exceeding the upper limits. Dr. Cañez answered that for 

the field fortification sample, the AHETF conducted a thorough investigation to try to determine 

what the issues were; they were not limited just to California. Techniques have been revised, and 

sealed ampoules will be used in the future to get better results in the correct range. As far as the 

strata, that depended on what the grower was planning to do on the day of the study. Rather than 

cut the growers’ day short, the data were simply collected. Dr. Lebowitz asked if the field 

fortification samples show residues or excessive residues, and whether the exposure data are 

adjusted accordingly. Dr. Cañez responded that this had been discussed with EPA, and if the 

values were systemically high, the AHETF likely would adjust them, but this would be done on a 

case-by-case basis. He was unsure whether the values were adjusted in this case. 

Dr. Popendorf noted that specialized equipment used for low rate productions might fall 

into a lower stratum, and this was not part of the protocol. He asked if there was any information 

that would indicate that atypical equipment exists, specialized at the low end or otherwise, that 

was not assessed. Dr. Cañez replied that one or two experts asked about the equipment responded 

that it was not typical. In clarifying those responses, however, it was determined that there were 

many specialized sprayers and electrostatic sprayers that are meant to reduce exposure that were 

not captured in this protocol because the AHETF was not examining engineering controls. 

Dr. Manautou asked if Dr. Cañez could explain why some samples are weathered and 

others are not prior to analysis. Dr. Cañez responded that it concerns when the sample could be 

contaminated or what residues could fall on the sample before the time it is actually collected, 

but for the hand washes and face/neck wipes, the samples are collected when they are taken, so 

those are not weathered. For the worker and WBDs, the residues could be present at minute one, 

but they will not be collected until the 4 hours are completed, so these samples are weathered, as 

are the samples in the OVS tubes. Dr. Manautou questioned whether the time of weathering was 

intended to mimic the length of time that a worker was in the field. Dr. Cañez replied that it was. 

The field fortification samples are prepared around the time the worker enters the field, and are 

collected when he/she comes in from the field. 

Dr. Lebowitz asked for the upper range of the length of time that samples are stored 

before they are analyzed. Dr. Cañez answered that he would have to examine the analytical 

reports, but source stability data are available to indicate stability in all of the products. Dr. 

Lebowitz confirmed that the data in the reports are adjusted for the stability deviations. Dr. 

Cañez responded that he did not think that they were adjusted, but sufficient (80 to 100 % 
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recoveries) stability of the samples is demonstrated. In selecting surrogates, the AHETF 

examines stability and determines whether the material can be analyzed and the level of 

recovery. 

Dr. Sharpe inquired about subject A4 in the Washington apple study who was observed 

not wearing gloves and the significance of the higher exposures related to the incidental 

exposures. Dr. Cañez responded that he did not know how the residues relate to the average, but 

the AHETF likely would determine the distribution of the residues, highlight some of the issues, 

and recommend that he wear gloves. Dr. Northington Gamble asked why the worker was not 

wearing gloves. Dr. Cañez assumed that it is his normal practice. The AHETF is trying to let 

subjects do their jobs in their normal manner. The subjects are provided with the product label 

when they start and researchers ensure that they read and understand it, but then they are allowed 

to conduct their normal practices. Dr. Popendorf noted that the protocol stated that the subjects 

were supposed to wear gloves when they were out of the cab, and asked if workers were told to 

follow the protocol. Dr. Cañez answered that part of the informed consent process is ensuring 

that the subjects understand the label requirements and what they are supposed to do. 

Public Comments

Dr. Cañez noted that EPA’s reviews had highlighted some issues that need to be changed, 

and as always the AHETF is willing to adapt and make this a process where deviations are 

reported. 

Dr. Philpott invited additional public comments on the AHETF closed cab airblast 

applicator study; none were received. He noted, however, that one written comment was received 

in response to the Federal Register notice of the meeting. Ms. Barbara Sachau, writing under the 

alias Jean Public, raised some issues regarding EPA’s failure to consider human exposures to lead 

through consuming hunted game. Dr. Philpott commented that this was not directly relevant to 

the issues before the Board, and probably was beyond the purview of EPA. 

Charge Questions

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

1. Was the research reported in the AHETF completed monograph report and 

associated field study reports faithful to the design and objectives of the protocol, 

SOPs, and governing documents? 

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

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

exposure of those who apply conventional pesticides with closed cab airblast 

equipment? 

3. Does available information support a determination that the studies were 

conducted in substantial compliance with subparts K and L of 40 CFR part 26?
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Board Science Review

Dr. Philpott requested the Board members focus their discussion on the two scientific 

charge questions. Additional suggestions or recommendations can be submitted independently to 

the Agency or can be elaborated in the meeting report. 

Dr. Lebowitz noted that Board members previously had discussed definitions of the terms 

in the charge questions. He believed that EPA’s scientific reviews and analysis were well done. 

The studies were not totally faithful to the protocol and SOPs, however, and possible adjustments 

were not made. In some cases, estimating changes in exposures from hand contact could have 

been improved. He believed that the MEA was insufficient and must be examined. Once the 

MEA is more accurate, proportionality can be examined better. The statistical methods used were 

not necessarily ideal, and other probability distribution functions might be better. Data were 

anchored by using half the level of detection and level of quantitation, and this is inappropriate 

because it gives false regression results. Once further analyses are conducted, the data will be 

useful and the Agency will have characterized the estimated exposure adequately for those who 

apply conventional pesticides with closed cab airblast equipment. The data then will be useful for 

regulatory purposes.

Dr. Manautou stated that he was confused with the analysis showing dermal data are 

independent from exposure and the inhalation data are not. He requested better clarification on 

this point. Some of the deviations from the protocol are not that significant, so he concurs with 

Dr. Lebowitz on his assessment, but there may be a need to anchor the dermal versus inhalation 

data. 

Dr. Fernandez noted that he had nothing further to add in terms of statistical analysis. 

Dr. Johnson stated that the use of the term 80 percent power needs to be qualified every 

time it is used. The tables that involve the geometric standard deviation (GSD), intra-class 

correlation (ICC), geometric mean, arithmetic mean, and 95th percentile show CIs for those that 

may not be CIs, because a CI would imply that sampling is being conducted from a single 

population. In this case, sampling is being conducted from 25 different populations. The 

population varies for each cluster, and the AaiH is varied for each subject. The 95 percent may be 

the observed distribution. In addition, the log normal probability plots were surprising because 

the data fit so well. It would be useful if the symbols corresponding to each study site were 

added to the normal probability plots. He would like to see another normal probability plot that 

corresponds to the AaiH subgroup to determine if there is any pattern. The EPA presentation did 

not focus on the cab exits versus exposure, but the report went into more detail. Those analyses 

are interesting, but he cautioned that EPA must be careful about making any inferences from 

discoveries that the experiment was not designed to address. The governing document satisfies 

references for 1.4 for the CI width to the 80 percent power, but this should be referenced in the 

report. In the regression analyses, it might be useful to look at the residual plots, conduct the 

regression, regress the log exposure, then examine the residuals from the regression to determine 

if there are any outliers or worrisome trends. 
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Dr. Young noted that when she examined the residuals, stated outliers did not appear to be 

outliers. It may be a consequence of them being from 25 different populations that caused them 

to appear to be outliers in the original plot. Dr. Fernandez rightly had raised a question about the 

slope being the same for each study site. Dr. Young conducted an analysis on that and there is no 

evidence of difference. The variance component is estimated to be zero, but EPA should check 

this in future analyses. Regarding the figures in the tables mentioned by Dr. Johnson, one of the 

problems is that it is deliberative to get a spread of the AaiH, and as a consequence, that affects 

exposure. What does the average of all of those exposures mean, and does it represent anything 

of interest? This raises a concern about the stated first objective, and EPA should consider what 

the measures of geometric mean or arithmetic mean really indicate in this case, and is it what the 

sponsors are interested in? Her other broad comment was that, in general, the analysis should 

reflect the study design. She indicated that the analysis performed does reflect the study design, 

but other issues were included as well. It is fine to explore other issues, but it must be ensured 

that the appropriate model that reflects the design is used for the principal analysis. 

Dr. Popendorf observed that on the air sample that was not used, it is correct that the 

sampling time is necessary to calculate concentration, but if the formula on page 10 of the report 

is used, the sampling time is not needed. The sample, then, still is valid as long as it ran for the 

entire application period, and such samples could be used in the future. He expressed concern 

that the hand contact was not discussed until the scientific review of the monographs (section 

2.3). He had examined hand versus non-hand contact, and noted that the 10 subjects he found 

with hand contact showed a big difference, but one that was not statistically significant. EPA was 

correct to examine the number of cab exits and entrances, and might consider examining the 

correlation by running the residuals and a step-wise regression to see if the remainder correlates 

with the AaiH after taking out the effect of exits and entrances. Additionally, the protocol did not 

account for any assessment of what residue might be inside of the cab, and there may have been 

a fair amount. A wipe sample could have been taken or the history of vehicle use could have 

been reviewed. He ran a correlation with time inside the cab; it was significant and might 

correlate with residues present. This should be mentioned as a study limitation. When the open 

cab study is reviewed, the correlation may be present. 

Dr. Chambers commented that in this case, the engineering control is so effective that the 

measured residues seen are from incidental exposures, and are not predictable. Therefore, the 

data sets will not be invalid if the proportionality is not seen. 

Dr. Philpott stated that with respect to the science charge questions, the conclusion was 

that the study was not totally faithful to the protocol, SOPs, and governing document, but that 

there are adjustments that can be made, such as estimating changes in exposure due to hand 

contact that fell outside the protocol and other protocol deviations, that will give better estimates 

of exposures. The Agency characterized the limitations of the data very well. There were 

recommendations on some of the analyses; for the most part, the statisticians on the Board were 

pleased, but it was suggested that some terms be more clearly defined. If 80 percent power is 

used, what it is used for should be explicit. In addition, there were questions about the use of 

95 percent CIs when sampling more than a single population. Although it was interesting that the 

additional exposures showed a correlation between dermal exposures and the incidental contact, 

it should be ensured that the analysis always reflects the principal points and objectives of the 
13

study design. The focus on cab entrances and exits was interesting and some potential analyses 

would be useful. Even if proportionality does not hold for the dermal exposure, the data still 

would be useful for the purposes of the task force and the Agency, and may suggest that 

engineering controls are effective. 

Board Ethics Review

Dr. Jerry Menikoff noted that available information supports a determination that the 

studies were conducted in substantial compliance with subparts K and L of 40 CFR part 26. He 

thanked EPA and Ms. Sherman for discussion of the detailed facts. The study is being conducted 

to answer a research question, and there are rules related to protection of subjects, but the point 

of the endeavor is not to protect the subjects; they should be protected consistent with the attempt 

to answer the research question. The overall design of the studies highly minimizes risks to 

subjects by creating a scenario in which, for the most part, subjects are doing what they normally 

do day to day. One major issue is the number of instances in which subjects did not wear gloves 

in a particular scenario; Ms. Sherman asked whether the goal of the research was supposed to be 

realistic and take into account what the subjects actually do while on the job. Subjects were 

informed that PPE should be worn, and they reviewed the consent form; it appears that workers 

do not always wear their gloves. Six out of 24 subjects removed their gloves in at least one 

instance. The protocol could have been written in a way that would not have made this a 

deviation, but the removal of gloves is not a significant ethical issue. He noted that these 

compounds were chosen because they were relatively low risk. The protocol does currently seem 

to state that each time a subject removes PPE, he/she should be warned. This is an issue that 

should be clarified in the future. 

Dr. Sharpe agreed that the study was conducted in substantial compliance with subparts K 

and L of 40 CFR part 26. Her impression on the issue of the workers not wearing their gloves is 

that it was just sloppiness. She is unsure whether or not it was sloppy on the part of the observer 

because the observer understood this to be strictly an observational study, which it was not. This 

issue does not, however, rise to the level of risk. Understanding the research as observational 

could be considered self-serving, because it provides additional data that the researchers were not 

seeking explicitly. It would be interesting to discuss whether this series of incidents should result 

in an SOP with additional guidance recommended to observers when they witness such 

behaviors. She is troubled if there are observers who are not trained sufficiently or do not have 

sufficient judgment to maintain the protocol requirements. That may in some cases, although not 

in this case, have implications on subject safety.

Dr. Northington Gamble suggested that some additional information could have been 

obtained by the observer as to why the subject was not wearing gloves, and she found it troubling 

that the observer did nothing. 

Dr. Philpott stated that the Board must decide whether the HSRB will be making the 

recommendation that the sponsor and the Agency consider drafting an SOP about creating a 

threshold for when intervention should occur. That is a difficult question, but gets to the point 

about variation among the observers and their understanding of the research goals. Without the 

SOP, variability could be introduced, and that could influence the study results. 
14

Dr. Popendorf reminded members that during the past year a protocol came to the Board 

in which clarification was requested on the same point: if a subject violated the protocol, how 

severe would the violation have to be before the person was not used as a subject?

Dr. Philpott did not know whether that issue had been resolved. He believed a suggestion 

was made to the Agency and sponsors that they determine some objective criteria on when 

subjects should be excluded from participation because of their behavior. In this case, the Board 

is asking whether criteria are needed for when observers should intervene to correct potentially 

dangerous behaviors in the subjects, recognizing that some of these behaviors represent normal 

activity, which is exactly the data that the Agency and sponsors hope to collect. 

Dr. Menikoff agreed that this is a relevant issue and suggested that it may be useful for 

sponsors to collect data from the person who is not wearing gloves; the protocol should not overinstruct subjects to a point of getting unrealistic behavior. There are other design elements in the 

study that correct for most of the egregious behavior. Subjects are well-trained and have been 

doing the studied work for 3 or more years. It may not be the Board’s place to tell the sponsor 

how to resolve this other than stating that it is a protocol issue. Scrupulous protocol adherence 

would have been for observers to warn subjects to put on PPE, but this may produce data largely 

deviant from what applies in the field. 

Dr. Philpott stated that the Board’s conclusion is that yes, studies were conducted in 

substantial compliance with subparts K and L of 40 CFR part 26, and that acknowledging the 

protocol deviations, the HSRB agrees with EPA’s assessment that they did not substantially 

increase risk to participants or compromise their safety. More importantly, the Agency and 

sponsors must consider whether they want absolute adherence to the current SOP that states that 

if there is deviation from the label, there will be an intervention, or whether they want to modify 

the SOP to reflect more accurately day-to-day practices on the part of the pesticide handlers. The 

HSRB is not making a recommendation either way, except to say that this point needs to be 

considered. There is consensus that the Board carefully would consider changes to the SOP to 

reflect actual conditions if there were potential risks, but it is not making any specific 

recommendations at this point. 

Session 2: AHETF Scenario Design and Associated Protocol Describing Proposed Research 

to Monitor Exposure of Workers Who Mix and Load Pesticides Formulated as Wettable 

Powders

Background

Ms. Sherman informed the Board that this protocol was similar to one reviewed in 

October 2010 for wettable powder (WP) in water-soluble packaging. This protocol is similar in 

that: design objectives, sample size, and rationale are similar to several previous AHETF 

scenarios reviewed; there is a 5x5 cluster configuration; and protocol procedures related to 

ethical conduct are similar. It differs from other AHETF protocols in that: one of the five 

clusters, a preexisting pre-rule study using diazinon as the surrogate already is completed; it 

monitors mixers and loaders; and it uses three new surrogates, dimethyl tetrachloroterephthalate 
15

(DCPA), sulfur, and thiophanate-methyl (copper was originally a surrogate, but was withdrawn). 

The protocol submission contained all elements of documentation required by 40 CFR §26.1125 

in the form of one main submission document and a supplement. This protocol was submitted to 

the Agency in early October 2010 before the previous HSRB meeting, so instead of rewriting the 

protocol, the AHETF included the supplement to reflect the changes suggested by the Board in 

October 2010. EPA believes that this proposal is ready for HSRB review. 

EPA Science Assessment

Mr. Jeffrey Evans (OPP, EPA) agreed that the protocol was very similar to the one on 

WPs in water-soluble packaging. WPs are the most basic simple formula available, and are 

widely used in agriculture. The scenario uses a single layer of clothing, long pants, long-sleeved 

shirt, shoes, and socks, and the only required PPE is chemical-resistant gloves. Dust masks and 

protective eyewear can be worn if subjects choose. There are three sub-scenarios that are used to 

account for the fact that there are differences in the way that the material is added to the tank. 

They include mixing of WPs: directly into the tank used for the pesticide application; into a large 

―pre-mix‖ tank at the same concentration to be applied to the crop by a number of application 

types; and into a tank or bucket as a concentrated slurry that must be further diluted and 

transferred to the final application tank.

There will be five clusters containing five monitoring units (MUs) each. The existing 

study (AHE39), completed before the enactment of EPA’s rule, involved the mixing and loading 

of a WP formulation of diazinon. This study included WBD and all body parts were accounted 

for in terms of measurement. Potential drawbacks, however, include lack of the Board’s input in 

terms of the statistical design, the narrow range of AaiH mixed and loaded (59 to 138 lbs ai) and 

the fact that the study consisted of only one sub-scenario (concentrate in pre-mix tank or bucket). 

That study will be added to four new clusters with five MUs each. EPA insists that all three subscenarios be performed at each new cluster, and notes that respirators may be required with 

certain products. 

EPA hoped that copper would have been included among the surrogates, but the 

interferences of copper on the WBDs from pre-washing were too significant. The three 

surrogates that will be included in the new clusters are: DCPA (dacthal), an herbicide with low 

dermal toxicity (but requiring a respirator for mixing and loading WPs because of inhalation 

toxicity) used on many vegetable crops; sulfur, a fungicide and insecticide having high 

application rates and low acute toxicity; and thiophanate-methyl, a widely used fungicide, but 

with AaiH in this study limited to 100 lbs because of exposure estimates. It is suggested that 

thiophanate-methyl be used for the lower strata. 

The proposed AaiH strata include the following requirements: all monitoring durations 

will be at least 4 hours; each subject will mix and load at least three tanks of spray mixture; and 

five strata of AaiH will be included in each cluster. The proposed monitoring areas ensure 

diversification of equipment types by including different growing regions of the country, 

different crops, and different climates. Given the limitations of AHE39, the researchers must 

ensure that each of the three sub-scenarios be monitored at least once within each cluster, and 

that participants apply AaiH from each of the five strata per cluster.
16

EPA Ethics Assessment

Ms. Sherman presented EPA’s ethics assessment. She began by noting that the current 

data on this exposure scenario do not meet contemporary standards, so newer and better data that 

would be generated through this research are needed to support EPA risk assessments. The 

research will be combined with existing data and used to estimate dermal and inhalation 

exposure for a wide range of pesticides. The subjects in the study will be recruited from growers 

and commercial pesticide application companies; once eligible growers are identified, the study 

director will seek permission to approach the employees to recruit subjects. Recruitment will 

take place with the use of a flyer posted in the workplace, or the study director will hold a 

meeting with interested employees to discuss the study and answer questions. Employers are not 

to attend recruitment meetings. Subjects who have experience within the past year performing 

mixing and loading with a WP product and who meet other eligibility criteria are recruited. The

protocols and SOPs provide procedures to protect employees from potential employer coercion. 

Employers are asked to sign a non-coercion statement affirming that they will not coerce or 

influence their workers in their decision whether to participate, and also must agree that they will 

provide alternate work on study days to workers who choose not to participate. They also agree 

that the decision to participate will have no impact on the employees’ future employment. 

The consent process consists of a private meeting between the study director and subject. 

There are equivalent processes in the protocol and SOPs for Spanish and English speakers 

relying on bilingual investigators to perform the meetings in Spanish. The consent form contains 

all of the elements required by 40 CFR §26.1116, and Ms. Sherman concluded that the 

organization and presentation of risk information in the consent forms are acceptable. 

In terms of respect for subjects, the payments proposed are reasonable, subjects are free 

to withdraw from the study at any time for any reason, individual results will be provided to 

subjects upon request, medical care for research-related injuries will be provided at no cost to the 

subjects, and there are procedures to protect subject privacy related to participation in pregnancy 

testing. The four overarching considerations in evaluating the recruiting consent process are met: 

subject selection is equitable; subjects are given the opportunity to make a fully informed choice 

about participation; participation is fully voluntary; and there is respect for subjects. 

In response to comments that the Board made in October 2010, risk of exposure to 

surrogates has been added back into the discussion of risk in the protocol and ICFs. Ms. Sherman 

concluded that the procedures in place minimize the risk related to participation in the study to 

the greatest extent possible. To minimize the risk of exposure to the surrogates, the researchers 

are using materials that have been widely tested and are proposing to have the subjects use them 

at levels associated with safe exposures. The participants will be selected from workers with 

experience performing the work being monitored, and they are therefore less likely to misuse the 

chemicals. Before the study begins, the participants will be reminded about safe practices and 

procedures and to wear appropriate PPE. 

In terms of heat-related illness, exclusion and eligibility criteria only allow subjects who 

are reported to be in good health. Subjects are closely observed during the monitoring period, 
17

and research staff are trained to recognize signs and symptoms of heat illness. There will be 

medical staff onsite and a stopping rule stating that the exposure monitoring will be stopped if 

the heat index exceeds 105 degrees Fahrenheit. A question was raised in October 2010 about who 

would make the determination that a subject would be considered too ill to make a rational 

decision about declining medical care; the medical professional onsite would make that 

determination. 

The risk of scripting field activities is expected to be small because the workers are not 

being asked to use equipment that they are unfamiliar with but may result in them applying more 

pesticide or working longer or shorter than they would have otherwise, and the extended work 

period could raise the risk of related illness. The psychological risk is minimized by providing 

for private handling of the pregnancy testing results and having a same-sex researcher present 

during dressing in the dosimeters. Risk of skin irritation from exposure to surfactants (soap for 

hand, face, and neck wash) is expected to be small. 

EPA concluded that the protocol provides a favorable risk-benefit balance. Subjects will 

be monitored while they perform their normal work so risks will not be much greater than what 

they would face normally. Although there are no direct benefits to the subjects, the risks have 

been properly minimized and therefore will be reasonable in light of the potential societal 

benefits of more accurate risk assessments from the generated data.

The AHETF has been responsive to EPA and HSRB comments in its supplement to the 

protocol. The task force has identified exposure to surrogate chemicals as a potential risk of 

study participation. When instructed to ask potential participants about what PPE they normally 

wear in a non-directive manner, the AHETF noted that this was its normal practice. EPA 

suggested that the AHETF revise its SOP on this process to acknowledge this concern. Because 

of the Board’s recommendation, the AHETF’s protocol now states that hand washes will be 

conducted before eating or smoking. EPA raised the issue that the AHETF should clarify whether 

hand washes will be required before water breaks. Requiring hand washes before every water 

break could result in additional exposures to the surfactants, however, and therefore may make 

subjects hesitant to take a water break. Conversely, not requiring the hand washes may increase 

hand-to-mouth exposure and may confound the results if some of the subjects are conducting 

hand washes but others are not. The next Board comment suggested that the AHETF address 

how individual exposure information will be released to subjects who request it, and asked that a 

check box be included on the ICF. In addition, the Board recommended that the task force 

explain how exposure information will be provided to subjects who might not speak English 

and/or are illiterate. This issue has not yet been addressed. There is an HSRB working group on 

the topic that will provide advice when available, so Ms. Sherman recommended that the AHETF 

incorporate that advice and the process into an SOP. The task force will test the 

representativeness of the sample and the accuracy of Spanish translations; EPA suggested that 

these actions be added to the SOPs. ICFs now explain that the researchers provide the pregnancy 

tests, and explain when the test will occur. Additionally, it has been clarified that individuals who 

are exempt or performing work not covered by the WPS are eligible to become subjects without 

WPS training. 
18

IIRB reviewed and approved the protocol, and its roster and Human Research Protection 

Program plan are on file with EPA and have been provided to the HSRB. The protocol is a 

proposal for third-party research involving intentional exposure of human subjects to a pesticide 

with the intention of submitting the resulting data to EPA under the pesticide laws. The primary 

ethical standards applicable to the conduct of this research are 40 CFR 26, subparts K and L and 

the Federal Insecticide, Fungicide, and Rodenticide Act 12(a)(2)(P). EPA concluded that the 

protocol meets the applicable ethical requirements of 40 CFR 26, subparts K and L, and did not 

note any deficiencies. 

Board Questions of Clarification

Dr. Popendorf sought justification for the upper range in the protocol, and asked if 

achieving it was feasible. Mr. Evans responded that EPA believed that it was. The AHETF is 

fully aware of the values EPA uses in its assessments. Given the application rates of sulfur, it is 

quite feasible for workers to get into the high range (604 to 2,000 lbs ai handled). Sulfur is 

applied at the rate of approximately 8 lbs per acre. Dr. Popendorf commented that he had not 

noticed the language in the protocol stating that each new cluster will have all three subscenarios. Mr. Evans replied that he remembered reading this, but that EPA was insisting on this 

point. Dr. Popendorf asked if there was a reason that all new clusters will contain all five strata. 

If that is done, the results will be a 4-4-9-4-4 distribution. Within Appendix C, the modeling 

came up with a factor of 3. They looked at clusters, and the distribution of MUs in clusters, but 

Dr. Popendorf did not know if strata were included. If they are, would the resulting 4-4-9-4-4 

distribution violate the broad criteria that structured the factor of three? Mr. Evans answered that 

it was impossible for EPA to know what will happen, but diversifying the strata is key for the 

secondary objective. If 20 MUs are fully diversified, the limitations of the five existing MUs 

would be minimized. Dr. Popendorf suggested that unless there was some rationale for repeating 

the middle strata, the researchers should use the five from the existing study and distribute the 

next 20 MUs throughout the other four strata. Mr. Evans asked if this would affect ICC analysis. 

Dr. Philpott suggested that this be addressed during the Board’s discussion period, and noted that 

two questions posed could be better asked of the AHETF. 

Dr. Sharpe noted that one of the slides in EPA’s presentation stated that respirators may 

be required for certain products, and asked if this would be clarified in terms of which chemicals 

would require a respirator. All of the photographs in EPA’s presentation showed workers using 

respirators. Mr. Evans answered that many times, the requirement for a respirator is based on the 

acute toxicity of the unused product. There are many products of this type, so it is likely that 

some are based on the concentration. 

Dr. Sidney Green pointed out that on page 19 of the protocol, in text discussing overhead 

cost associated with obtaining efficient configuration, the last two sentences in the paragraph 

carried over from page 18 seem to be incorrect. Should it state ―monitoring areas less costeffective‖? Mr. Evans agreed that the text was confusing. Dr. Green also questioned if in the 

table on page 31, the entries on sulfur and total ai usage on strawberries and cherries were 

incorrect, because all other entries were in descending order of amount. Mr. Evans admitted that 

this would be answered better by the AHETF. Dr. Green noted that the last confusing instance 

was on page 273 in the SOP. On the third line of paragraph B, the study mentions ―drug and 
19

device‖ procedures. There are no drugs and no devices in this protocol. This procedure may have 

come from the U.S. Food and Drug Administration’s (FDA) guidelines. He suggested that ―drug‖ 

and ―device‖ are inappropriate in this instance, and ―chemicals‖ should replace them. Mr. Evans 

agreed. Dr. Philpott suggested that this was a recommendation for the sponsor. 

Dr. Manautou asked if there was any relevance of the crop type to the proposed protocol. 

Mr. Evans responded there was not, but various crops allowed an opportunity to find participants 

who use one of the surrogates and the ability to find at least five different equipment types. 

Dr. Popendorf questioned why subjects may be asked to work longer than they normally 

would during the study. Ms. Sherman responded that this point was meant in relation to the 

concept of scripting their work for the day of the study; the time of monitoring and AaiH could 

be slightly more than under normal circumstances. Dr. Philpott added that the time required to 

put on the WBD may add time to the workers’ day as well. 

Dr. Northington Gamble noted the protocol’s mention of the use of witnesses for people 

of low literacy; it states on page 292 that the witness would be identified by the study director. It 

then lists the protocol that had been discussed previously by the HSRB on how the witness 

would be identified, which is in conflict with the previous statement. Ms. Sherman replied that 

the statement ―identified by the study director‖ may have been carried over from older protocols. 

She will examine the issue to see if the procedure is included in the SOP. The intention is that the 

worker can identify a witness of his/her choosing. Dr. Philpott stated that this may be a 

recommendation. 

Dr. Philpott invited Dr. Cañez to respond to Board questions on behalf of the AHETF. Dr.

Philpott asked whether having an upper limit of 1 ton of AaiH was feasible. Dr. Cañez answered 

that he could not name products that could be used at those rates, but when studies are designed, 

members are asked what products fall into specific categories. The AHETF will then examine the 

product labels and determine the ranges of AaiH needed. There may not be many that reach the 

higher limit in this protocol, but some may be in the higher strata. Dr. Popendorf asked if the 

products that might be used at the high level or information on how the level was determined 

were listed in the protocol. Dr. Cañez noted that it should be listed in the scenario design 

document. 

Dr. Philpott asked whether the modeling accounted for the fact that the pre-rule study 

(AHE39) was biased toward the middle strata, and whether that may affect the 5x5 cluster 

design. Dr. Cañez answered that for the cluster design, the AHETF depends on Dr. Larry Holden 

(AHETF Statistician, Sielken & Associates) to generate those monitoring areas and clusters 

taking into consideration the existing data. The study design document should contain an 

analysis of how the existing data can fit with the new protocol. 

Dr. Lebowitz asked which chemical surrogates will be used in which clusters because 

mixing scenarios differ. Dr. Cañez responded that it was known what crops the products were 

used in, and the AHETF will call many growers in those areas to achieve the diversification 

needed. It will be a challenging task. Some products that are used at very low use rates must be 

placed in the smaller strata, and those may be mixed directly into the tank. Some of the products 
20

that are used in the upper strata at higher use rates, such as sulfur, are more likely to be added to 

pre-mix tanks. 

Dr. Northington Gamble noted a discussion at the previous HSRB meeting on the 

selection of subjects who are in good health. In the protocol, it stated that people who say they 

are in good health are accepted, but there are no health criteria stated. Are there certain health 

conditions that would exclude someone from participating in the study? Dr. Cañez responded 

that the AHETF did not want to get into the practice of having criteria in the process, so subjects 

are allowed to self-report and must indicate that they have done the type of work being studied 

within the past year. Dr. Philpott commented that at the previous HSRB meeting, there was a 

concern about a participant who reported that he was in fair health, but was enrolled in a study 

anyway after the investigator met with him and made an assessment. The HSRB recommended 

that there be clear objective criteria as to what constituted good health. It may be something such 

as having engaged in the physical work within the past month, but the AHETF may want to 

consider some objective criteria. Dr. Northington Gamble added that if someone states that they 

are in fair health, they should not be included in the study. Dr. Cañez replied that in this protocol, 

there was not an option for ―fair health‖: the subject would identify as in good health or not in 

good health. Ms. Sherman added that there is an SOP (11.2.1) on worker health status that states 

that the workers must be in good health.

Dr. Philpott asked if the requirement of the respirators as PPE is chemical-specific or if 

all individuals would be required to wear respirators. Dr. Cañez responded that the AHETF was 

following the product label requirements. Dr. Sharpe asked if this would be reflected in the ICF 

and protocol, because she did not believe that it currently is included. Dr. Cañez answered that 

the informed consent process will include the label for the product that will be used, and the label 

requirements would be reviewed with the study candidate. 

Dr. Sharpe mentioned a new line in the paragraph about pregnancy testing stating that 

more than one pregnancy test may be required and asked for the reasoning behind that and 

whether it would be explained further in the ICF. Dr. Cañez stated that he was unaware of the 

line. Ms. Sherman added that she had seen the line and had a question about it as well. Dr. 

Philpott added that the HSRB had seen a study at a prior Board meeting in which there were 

multiple activities on multiple days; the way the regulation was written erred on the side of 

caution, and perhaps that was the source of the statement. Dr. Cañez added that it may have 

stemmed from the potential delay from the informed consent process to the actual monitoring, 

but that he would investigate. Dr. Sharpe added that it would be useful to explain the reasoning 

in the ICF if more than one test is required.

Dr. Philpott noted Dr. Green’s questions regarding an error on page 19 regarding costeffectiveness, and on the distribution of crops in a table on page 31. Dr. Cañez replied that it is 

more cost-effective to get more MUs in one place, but he would investigate the potential errors 

and get back to EPA. 

Dr. Johnson commented that section 4.5.1, pages 23-24 of the protocol, discusses the 

GSD and the existing study ICC and mentions a chi square distribution. He asked for either a 

greater explanation of the chi square, or that it be removed from the protocol. Dr. Young added 
21

that the GSD to the square root of 1-ICC was confusing, and a reference would be useful. Dr. 

Philpott noted that these were points to be addressed during the Board’s discussion period. 

Public Comments

Dr. Philpott called for public comments on the proposed AHETF scenario and field study 

(AHE80); no public comments were presented.

Charge Questions

Ms. Sherman read the charge questions into the record:

If the proposed AHETF scenario and field study (AHE80) is revised as suggested in 

EPA’s reviews and is performed as described:

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

exposure of workers who perform open mixing/loading of pesticide end use products 

formulated as wettable powders? 

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

K and L?

Board Science Review

Dr. Popendorf raised three points related to the strata. The upper 2,000 lb limit likely is 

reasonable when mentioning sulfur, but he could not find the reference to how that limit was 

generated in the protocol. The second point related to the lower estimate, and whether the 

equipment used is typical. Perhaps some of the limitations and what is not being assessed could 

be discussed. Thirdly, the guidance on pages 27-30 discusses addressing the issue of clusters, but 

did not address the use of strata. He noted that the way the next 20 MUs are distributed among 

the five strata is a concern; if they are uniformly distributed, a 4-4-9-4-4 distribution will be 

created, and this may violate the criteria in Appendix C. Additionally, it may not be good science, 

because too many data may be clustered in the middle. 

Dr. Green noted no concerns regarding the science associated with the scenario; his only 

concerns were the three issues to be clarified in the protocol and the SOPs. His response is yes, 

the protocol would provide scientifically reliable data.

Dr. Young stated that regarding Dr. Popendorf’s concern about the distribution over the 

strata, some simulations may have to be conducted. She believed, however, that he was right, and 

that the data will be too clustered in the center to give appropriate power. She reiterated her point 

about the GSD calculation, and also expressed concern about the chi square calculation; they 

need to be defined better. She added that if there is not an association between exposure and 

AaiH, treating it as a log normal and determining a mean is reasonable. If there is an association, 

however, taking an average is forcing more diversity than normally would be reflected in a 

sample, which may be useful. Dr. Young also stated that the sample should not be treated as 

random. Overall she felt the explanations were well-documented throughout the protocol. 
22

Dr. Johnson agreed that Dr. Young’s ideas about simulation could be useful for future 

studies. Additionally, the existing study had all mixtures as slurries, and this may raise the same 

issues as the distributions of MUs. Dr. Popendorf agreed, and asked that EPA ensure that this 

issue is in the final protocol; each cluster should have all types of mixing and loading performed. 

He also agreed that simulations would be useful, but suggested that they be run with five in each 

cluster, adding all the new MUs to the two lower and two upper strata. Because if the middle 

strata is doubled, power will be lost. Dr. Young agreed, and added that she questioned what it 

meant to average all of the different kinds of mixes and AaiH. Dr. Popendorf agreed that this was 

an unknown. Dr. Lebowitz also agreed, and added that the chemical used for each mixture might 

be important. With the slurry in the middle strata, adding data above and below will provide a 

good regression line. That may be worrisome based on the design, and a simulation may help to 

predict what might happen. Mr. Evans added that he had held several e-mail conversations with 

Dr. Holden, who stated that the AaiH levels tend to be forgiving to a point. The secondary 

benchmark often can be met if only some of the clusters span the practical range of AaiH. The 

separation into exact strata is less important than the ability to span the AaiH range. Mr. Evans 

found this compelling in terms of conducting the next four clusters as if there were five. 

Dr. Johnson noted that Dr. Holden seemed to agree with him and Dr. Young. 

Dr. Philpott stated that the Board’s general consensus regarding whether the research is 

likely to generate scientifically reliable data useful for assessing the exposure to workers under 

this scenario is yes, but with limitations. He noted that Dr. Popendorf had raised some concerns 

about how the range of the strata was generated, which was not clear to him in reading the 

protocol, and that each of the remaining four clusters must have all three of the sub-scenarios 

included. There seemed to be broad agreement that given the fact that the previous AHE39 study 

was biased towards the middle strata and only was a slurry scenario, it may be useful to conduct 

some simulations to determine whether the desired power can be achieved by just moving 

forward with the remaining four clusters across all five strata with all three sub-scenarios 

represented, or whether the remaining MUs should be distributed differently. The question was 

raised as to whether this distribution may affect the scientific validity of both objectives but 

particularly objective number two. There were concerns about how the GSD and the ICC 

calculations were conducted in Section 4.5.1 of the protocol, and a request for more explanation 

and some references for the calculations was made. It was stated that using a log normal is 

correct if there appears to be no association between exposure and the AaiH, but if there is an 

association, that raises questions about the appropriateness of treating a forced diversity sample 

as though it were random. He added that Dr. Green noted that there were some potential errors in 

the protocol, particularly with respect to cost effectiveness on page 19, the crop distribution table 

on page 31, and concerns about the language used for adverse event reporting that seems to be 

language from the FDA.

Dr. Popendorf asked that the rationale for the 2,000 lb upper limit in the protocol be 

pointed out, and that if it was found, that the final meeting report reflect that he had missed it. Dr. 

Philpott explained that the Board’s recommendations are not finalized until the final meeting 

report is released. The draft report will be discussed during a public teleconference. Therefore, if 

Dr. Cañez or Mr. Evans can identify the area concerned in the protocol and notify him and Mr. 
23

Downing via e-mail, the response will be forwarded to Dr. Popendorf and that recommendation 

can be removed. 

Board Ethics Review

Dr. Northington Gamble stated that the research is likely to meet the applicable 

requirements of 40 CFR part 26, subparts K and L if some issues are resolved. One point is to 

ensure that people are fully informed of their choice to participate. To have the best practices in 

terms of informed consent, the discussion must consider more than ethics, and in this case must 

consider literacy, which often is conflated with reading. The following definition of health 

literacy is from the Department of Health and Human Services’ national action plan on health 

literacy: ―the degree to which an individual has the capacity to obtain, communicate, process, 

and understand health information and services in order to make appropriate health decisions.‖ 

Literacy is not just about reading, but also about comprehension. The words ―illiterate‖ and 

―non-reader‖ should not be used; instead use terms such as ―low literacy‖ or ―limited literacy.‖ 

These should be changed in the protocol, as should statements such as ―the reading level of the 

English speakers was appropriate.‖ The actual reading level should be defined in both English 

and Spanish, and Spanish used should be defined by dialect. 

Dr. Northington Gamble added that the change to the language about refusing medical 

treatment must be revised. The use of the term ―rational decision‖ is a concern. EPA approached 

some other points of revision well, such as the language surrounding the PPE that subjects 

normally wear while working, and the fact that hand washing before water breaks needs to be 

clarified. 

Dr. Sharpe agreed that more modifications are needed so that the protocol and ICF will be 

in compliance with the regulation. She asked Ms. Sherman about the identification of the return 

of research results as an indirect benefit of the study to participants in EPA’s review. The study 

states that there are no benefits to the subjects, and Dr. Sharpe agreed, and believes that EPA 

should remove the statement from its report. Her other point involves the protocol identifying the 

study as greater than minimal risk on page 106 and again in the supplement. If the surrogate 

chemicals are to be added as one of the possible risks, the addition must be made in a number of 

different places in the protocol and in the SOP. The protocol now states that the study is of 

greater than minimal risk in particular because of heat-related illness, which is too narrow 

because the addition of the surrogates as a potential risk needs to be reflected in the protocol, the 

SOP 11.J.2, and the informed consent checklist. The governing document states that the AHETF 

does not consider the risk of toxicity for pesticide handling to be strictly due to study 

participation, but it is if the study includes surrogates. 

Dr. Chambers stated that her understanding was that a pesticide would be applied to that 

field with or without the study, and it could be the same one or a different one. These workers 

would be doing their normal tasks, perhaps with this chemical or perhaps with another one. They 

may or may not be doing something different in the study than they would otherwise. 

Dr. Philpott noted that a risk of study participation is that participants may be using a 

surrogate compound that they normally would not use, and handling different amounts or using 
24

equipment that they normally would not use. Dr. Sharpe has stated that the AHETF must go back 

through all of the SOPs and documents to ensure that exposure to the surrogate pesticide is 

classified as a risk. Dr. Sharpe added that other areas may need to be modified because of the 

addition of that potential risk.

Dr. Popendorf commented that there are several uses of the word ―surrogate.‖ In some 

cases a chemical other than the pesticide in question is a surrogate. The data that result from this 

use are considered surrogate data for any other pesticide. Dr. Sharpe clarified that she was using 

the word in the first way Dr. Popendorf mentioned. Dr. Popendorf added that in this case, the 

participation of the subject is predicated on the fact that they are going to apply the pesticide to 

be studied. 

Dr. Philpott stated that the recommendation about adding the risk of surrogate chemicals 

to the protocol was made at the last Board meeting for the previous protocol. The 

recommendation can be made for this protocol as well. Dr. Sharpe noted that Dr. Popendorf had 

explained that it may not be applicable in this study. 

Mr. Jordan confirmed that the task force drafted the protocol and submitted it to EPA 

before the October 2010 HSRB meeting, and that is why the protocol did not include any 

reference to surrogate chemicals and the risks associated in either the informed consent materials 

or the assessment of risks and benefits. The task force submitted a supplement to the protocol, 

which contained language about how they would amend the informed consent documents to 

address that consideration. EPA is considering the point that Dr. Menikoff raised in October 2010 

and that the Board accepted and endorsed in its meeting report; by asking participants to use 

pesticides that they might normally be using but by constraining that use through the scripting 

process, the exposure profile might differ compared to what those participants would have 

experienced otherwise, which might amount to a difference in risk. The pesticide use that would 

go forward under the protocols would be consistent with the product labeling and would have an 

acceptable level of risk.

Dr. Popendorf pointed out that Mr. Jordan never used the term ―surrogate,‖ so what he 

said would apply to any study that involved exposure to pesticides. Mr. Jordan noted that in 

EPA’s parlance, the word surrogate is used to mean that the chemical tested will be used to 

represent other pesticide chemicals. 

Dr. Philpott added that ―surrogate‖ is being used in multiple ways across multiple studies, 

and the Board members must be careful as to how they use it. 

Dr. Chambers postulated that an insecticide is needed on a particular field of the grower 

that is participating. He has a choice of several that are approved for that purpose, but there is 

only one surrogate like carbaryl, in this case, that is stable and analyzable enough to serve as the 

surrogate. So carbaryl is used but others could have been used as well. She thought that this was 

the reasoning for the use of the term ―surrogate.‖ Mr. Jordan responded that she was correct. The 

recruitment process asks growers what pesticides they use, and the investigators do not steer 

growers toward use of a chemical but rather narrow the pool of potential growers down by 

finding out what they use. 
25

Dr. Lux noted that the regulatory distinction between an intentional exposure study and 

an observational study is critical. If a study meets the regulatory definition of an intentional 

exposure study for any reason, including scripting, then the exposure becomes a risk of the 

research. In this study and in most of these studies, that research risk is very minor and is not the 

biggest risk of concern. By contrast, an observational study under the regulatory definition 

examines exposures that occur naturally without being in any way influenced by the research 

and, therefore, cannot be considered a risk of the research.

Dr. Northington Gamble commented that EPA’s review states that ―in this study, risks to 

subjects are classified as greater than minimal, primarily since agricultural work is considered a 

high-risk occupation where the likelihood of harm or discomfort is greater than what is 

encountered in ordinary daily life.‖ Therefore, all these studies could be said to have a greater 

than minimal risk. Dr. Lux explained that he used the term minor because minimal risk has a 

regulatory meaning that is highly contested in the bioethics community.

Dr. Sharpe confirmed that the outcome of this conversation may be a recommendation to 

go back to EPA’s report on page 15, and possibly the protocol on page 106, to examine if this 

minimal risk issue is accurately characterized consistent with what has been added to the 

protocol.

Dr. Philpott stated that this was a recommendation both to the sponsors to ensure that the 

risk of exposure to the pesticide is accurately reflected everywhere in the protocol and in the 

informed consent documents, and also a recommendation to the Agency to examine its review 

and how risks were characterized, particularly in terms of minimal or greater than minimal.

Dr. Sharpe added that on page 288 and in the supplement, there is an issue with how to 

phrase the paragraph stating that the medical professional onsite will provide care and decide 

whether subjects are too sick to make a rational decision about refusing medical treatment. She 

seconded Dr. Northington Gamble’s recommendation about the need for some criteria that are 

consistent with the literature about decision-making capacity. In terms of the word ―rational,‖ the 

recommendation may be to delete it. The medical professional needs to determine, based on 

medical criteria, that the person is too sick to make a decision.

Dr. Lebowitz agreed that medical criteria should be used because he assumed that 

medical personnel will use that rather than whether the person is rational enough. As a point of 

clarification, agricultural work presents a greater than minimal risk. Pesticide-specific usage 

causes a minor risk increase. The terminology has to distinguish between those two aspects. The 

terminology, however, is appropriate. 

Dr. Philpott noted that the following points should be included in the recommendations: 

the sponsor should define ―good health‖ as a criterion for study inclusion; explain why more than 

one pregnancy test may be required; and clarify in the SOPs that witnesses are to be chosen by 

subjects with low literacy versus study directors. The consensus of the Board is that the response 

to the question as to whether or not the research is likely to meet the applicable requirements for 

40 CFR part 26, subparts K and L is yes if the protocol addresses the concerns identified by Ms. 
26

Sherman in her ethics review and points raised by the Board members, including Dr. Northington 

Gamble’s input to ensure that literacy is not conflated with reading and that use of terms like 

―illiterate‖ or ―non-reading‖ can be considered offensive. Dr. Northington Gamble added that 

when asked if they are non-readers, subjects might say that they can read because of the stigma 

attached to being a non-reader. Dr. Philpott commented that sponsors also should be specific 

about what ―appropriate reading level‖ means, and ensure the dialect of Spanish used represents 

the dialect of the study population. In addition, ―rational‖ should be deleted from the concept that 

a medical professional may determine that a subject lacks capacity to make a ―rational‖ decision, 

and instead clear criteria for assessing capacity should be used. Also, investigators should ensure 

that discussions about PPE do not sway individuals to use different levels of PPE than they 

normally would to participate in the study; remove the return of results as a potential benefit as 

described currently until the workgroup makes recommendations about how those results should 

be returned and the ethical basis for providing that information to study participants; and ensure 

that exposure to the pesticide as a potential risk of study participation is added back into the 

protocol and SOPs.

Dr. Young stated that Mr. Sarkar had been helpful in explaining the derivation in 

question, but that has raised some other concerns that will be addressed in the final Board report. 

Dr. Johnson added that the section in question could be removed, and Dr. Philpott noted that may 

be the Board’s recommendation, but the Agency should wait until the final report containing the 

HSRB’s final recommendations is issued. 

Dr. Philpott thanked Board members, Agency staff, and public participants for their 

participation in the meeting and flexibility in completing the study reviews quickly. 

Preview of Upcoming Meetings

Mr. Downing announced that the next HSRB meeting would be held during the week of 

April 11-15, 2011, at a hotel in Crystal City, Virginia. The notice of the exact dates, times, and 

location will be published in the Federal Register and posted on the HSRB Web site.

Adjournment 

Mr. Downing adjourned the meeting at 3:17 p.m.

Respectfully submitted:

Jim Downing

Designated Federal Officer

Human Studies Review Board

United States Environmental Protection Agency
27

Certified to be true by:

Sean Philpott, Ph.D., M.S. Bioethics 

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.
28

Attachments 

Attachment A HSRB Members

Attachment B Federal Register Notice Announcing Meeting 

Attachment C Meeting Agenda 
29

Attachment A

EPA HUMAN STUDIES REVIEW BOARD MEMBERS

Chair

*Sean Philpott, Ph.D., M.S. Bioethics Term: 3/27/2006-10/31/2011

Director, Research Ethics

The Bioethics Program

Union Graduate College-Mt. Sinai School of Medicine

Schenectady, NY

Vice Chair

*Janice Chambers, Ph.D., D.A.B.T. Term: 3/27/2006-10/31/2011

William L. Giles Distinguished Professor

Director, Center for Environmental Health Sciences

College of Veterinary Medicine 

Mississippi State University 

Mississippi State, MS 

Members

*George C.J. Fernandez, Ph.D. Term: 5/1/2010-8/31/2013

Director, Center for Research Design and Analysis 

University of Nevada – Reno

Reno, NV

*Vanessa Northington Gamble, M.D., Ph.D. Term: 10/19/2009-10/31/2012

University Professor of Medical Humanities

Gelman Library

The George Washington University

Washington, DC

*Sidney Green, Jr., Ph.D., Fellow ATS Term: 10/19/2009-10/31/2012

Department of Pharmacology

Howard University College of Medicine

Howard University

Washington, DC

*Dallas E. Johnson, Ph.D. Term: 8/31/2007-8/31/2013

Professor Emeritus

Department of Statistics

Kansas State University

Manhattan, KS
30

*Michael D. Lebowitz, Ph.D., FCCP Term: 3/27/2006-8/31/2012

Retired Professor of Public Health

(Epidemiology) & Medicine & Research Professor of Medicine

University of Arizona

Tucson, AZ

*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

Jerry A. Menikoff, M.D. Term: 3/27/2006-8/31/2012

Director, Office for Human Research Protections

Department of Health and Human Services 

Rockville, MD 

*^Rebecca T. Parkin, Ph.D., M.P.H. Term: 10/1/2007-8/31/2013

Professorial Lecturer (EOH)

School of Public Health and Health Services

The George Washington University

Washington, DC

*William J. Popendorf, Ph.D. Term: 10/19/2009-10/31/2012

Professor Emeritus

Department of Biology

Utah State University

Logan, UT

Virginia Ashby Sharpe, Ph.D. Term: 5/1/2010-8/31/2013

National Center for Ethics in Health Care

Veterans Health Administration

Department of Veterans Affairs 

Washington, DC

*Linda J. Young, Ph.D. Term: 3/28/2008-8/31/2012

Department of Statistics

Institute of Food and Agricultural Sciences

University of Florida

Gainesville, FL 

*Special Government Employee (SGE)

^Not in attendance on January 26, 2011
31

Attachment B

Federal Register Notice Announcing Meeting

[Federal Register Volume 76, Number 8 (Wednesday, January 12, 2011)]

[Notices]

[Pages 2107-2109]

From the Federal Register Online via the Government Printing Office [www.gpo.gov]

[FR Doc No: 2011-625]

=====================================================================

======

ENVIRONMENTAL PROTECTION AGENCY

[EPA-HQ-ORD-2011-0970; FRL-9252-3]

Human Studies Review Board; Notice of Public Meeting

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

---------------------------------------------------------------------------------------------------------------------

----------

SUMMARY: The U.S. Environmental Protection Agency (EPA or Agency) Office of the Science 

Advisor (OSA) announces a public meeting of the Human Studies Review Board (HSRB) to 

advise the Agency on EPA's scientific and ethical reviews of research with human subjects.

DATES: This public meeting will be held on January 26, 2011, from approximately 8:30 a.m. to 

approximately 5 p.m. Eastern Time. The meeting will be held at the Environmental Protection 

Agency, Conference Center--Lobby Level, One Potomac Yard (South Bldg.), 2777 S. Crystal 

Drive, Arlington, VA 22202. 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 10 business days prior to the meeting to allow EPA 

adequate time to process your request.

 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.

ADDRESSES: Submit your written comments, identified by Docket ID No. EPA-HQ-ORD2011-0970, by one of the following methods:
32

 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-2011-0970. 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 

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 

disk or CD-ROM 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:

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) or the Federal Insecticide, 
33

Fungicide, and Rodenticide Act (FIFRA). Since other 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. EST, 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 mid 

January 2011. 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-

0970 in the subject line on the first page of your request.
34

 1. Oral comments. Requests to present oral comments will be accepted up to Wednesday, 

January 19, 2011. 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 request (preferably via e-mail) to Jim Downing or Lu-Ann Kleibacker, under FOR 

FURTHER INFORMATION CONTACT, no later than noon, Eastern Time, Wednesday, 

January 19, 2011, 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, January 19, 2011. 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 section 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 26, 2011, EPA's Human Studies Review 

Board will consider scientific and ethical issues surrounding these topics:

—A scenario design and associated protocol from the Agricultural Handler Exposure Task Force 

(AHETF) describing proposed research to monitor exposure of workers who mix and load 

pesticides formulated as wettable powders. EPA requests the advice of the HSRB concerning 

whether, if it is revised as suggested in EPA's review and if it is performed as described, this 

research is likely to generate scientifically reliable data, useful for assessing the exposure of 
35

those who mix and load pesticides formulated as wettable powders, and to meet the applicable 

requirements of 40 CFR part 26, subparts K and L.

—The report of a completed scenario monograph and study reports of five field studies from the 

Agricultural Handler Exposure Task Force (AHETF) measuring the dermal and inhalation 

exposure of workers applying liquid spray pesticides to tree or trellis crops using closed cab 

airblast equipment. The studies were conducted in five states in the U.S. where closed cab 

airblast equipment is commonly used in production agriculture. EPA seeks the advice of the 

HSRB on the scientific soundness of this completed research and on its appropriateness for use 

in estimating the exposure of workers who apply liquid spray pesticides using closed cab airblast 

equipment, and 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.

 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 

concerning a Board meeting report, if applicable, can be found at http://www.epa.gov/osa/hsrb/

or from the person listed under FOR FURTHER INFORMATION CONTACT.

 Dated: January 7, 2011.

Fred S. Hauchman,

Acting EPA Science Advisor.

[FR Doc. 2011-625 Filed 1-11-11; 8:45 am]

BILLING CODE 6560-50-P
36

Federal Register Notice Correcting Docket Number

[Federal Register Volume 76, Number 12 (Wednesday, January 19, 2011)]

[Notices]

[Page 3134]

From the Federal Register Online via the Government Printing Office [www.gpo.gov]

[FR Doc No: 2011-1062]

=====================================================================

======

ENVIRONMENTAL PROTECTION AGENCY

[EPA-HQ-ORD-2010-0970; FRL-9254-7]

Human Studies Review Board; Notice of Public Meeting; Correction

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice; correction.

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SUMMARY: The U.S. Environmental Protection Agency (EPA) published a document in the 

Federal Register of January 12, 2011, announcing the January 26, 2011 public meeting of the 

Human Studies Review Board. The document contained incorrect Docket ID Number.

FOR FURTHER INFORMATION CONTACT: Lu-Ann Kleibacker, 202-564-7189.

Correction

 In the Federal Register of January 12, 2011, in FR Doc. 2011-625, on page 2107, in the title, 

correct the ―Docket ID No.‖ to read EPA-HQ-ORD-2010-0970. On page 2108, in the first 

column, correct the ―Docket ID No.‖ to read EPA-HQ-ORD-2010-0970.

ADDRESSES: Submit your written comments, identified by Docket ID No. EPA-HQ-ORD2010-0970:

 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 
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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-2010-0970. 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 

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 

disk or CD-ROM 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. On page 2109, in the first column, correct the ―Docket ID No.‖ to read EPAHQ-ORD-2010-0970:

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-2010-

0970 in the subject line on the first page of your request.

 Dated: January 13, 2011.

Paul T. Anastas,

EPA Science Advisor.

[FR Doc. 2011-1062 Filed 1-18-11; 8:45 am]

BILLING CODE 6560-50-P
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Attachment C

U.S. ENVIRONMENTAL PROTECTION AGENCY

HUMAN STUDIES REVIEW BOARD

JANUARY 2011 PUBLIC MEETING AGENDA

Environmental Protection Agency (EPA) Conference Center

Lobby Level - One Potomac Yard (South Bldg.)

2777 S. Crystal Drive, Arlington, VA 22202 

Wednesday, January 26, 2011

9:15 AM* Convene Public Meeting and Review Administrative Procedures – Jim 

Downing (Designated Federal Officer, Human Studies Review Board [HSRB], 

Office of the Science Advisor [OSA], EPA)

Opening Remarks – Warren Lux, M.D. (Director of the Program in Human 

Research Ethics, OSA, EPA)

Introduction and Identification of Board Members – Sean Philpott, Ph.D. 

(HSRB Chair) 

Welcome and Follow-up on Previous HSRB Recommendations – Mr. William 

Jordan (Office of Pesticide Programs [OPP], EPA)

Session 1: Agricultural Handler Exposure Task Force (AHETF) report of a completed 

scenario monograph and study reports of five field studies measuring the 

dermal and inhalation exposure of workers applying liquid spray pesticides to 

tree or trellis crops using closed cab airblast equipment

9:35 AM EPA Science and Ethics Reviews – Mr. Matthew Crowley (OPP, EPA) and 

Ms. Kelly Sherman (OPP, EPA) 

10:35 AM Board Questions of Clarification – Sean Philpott, Ph.D. (HSRB Chair), EPA, 

Principal Investigator/Sponsor

11:10 AM Break

11:25 AM Public Comments 

11:35 AM Board Discussion – Science

Charge to the Board: 

Was the research reported in the AHETF completed monograph report and associated 

field study reports faithful to the design and objectives of the protocol, standard operating 

procedures, and governing documents?

Has the Agency adequately characterized, from a scientific perspective, the limitations on 

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

who apply conventional pesticides with closed cab airblast equipment?

12:35 PM Lunch
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1:30 PM Board Discussion Continued – Ethics

Charge to the Board:

Does available information support a determination that the studies were conducted in 

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

Session 2: Agricultural Handler Exposure Task Force (AHETF) scenario design and 

associated protocol describing proposed research to monitor exposure of 

workers who mix and load pesticides formulated as wettable powders

2:30 PM EPA Science and Ethics Reviews – Mr. Jeff Evans (OPP, EPA) and Ms. Kelly 

Sherman (OPP, EPA) 

3:00 PM Board Questions of Clarification – Sean Philpott, Ph.D. (HSRB Chair), EPA, 

Principal Investigator/Sponsor

3:30 PM Break

3:45 PM Public Comments

4:00 PM Board Discussion

Charge to the Board:

If the revised AHETF scenario and field study proposal AHE80 is revised as suggested in

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

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

exposure of handlers who perform open mixing and loading of pesticide end use products 

formulated as wettable powders?

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

and L?

5:30 PM Adjournment