Document ID: EPA-HQ-ORD-2010-0970-0034
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2011-03-01T05:00Z

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.

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 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 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 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-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 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. 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 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 % 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: 

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?  

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? 

Does available information support a determination that the studies were
conducted in substantial compliance with subparts K and L of 40 CFR part
26?

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. 

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 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. 

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 over-instruct 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 (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 sub-scenarios 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.

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, 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. 

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
sub-scenarios. 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
cost-effective”? 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 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 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 cost-effectiveness, 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 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:

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? 

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. 

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.
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 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. 

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. 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

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.

Attachments 

	

	

Attachment A 		HSRB Members

Attachment B 		Federal Register Notice Announcing Meeting 

Attachment C 		Meeting Agenda 

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

*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

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 [ 
HYPERLINK "http://www.gpo.gov/" 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-ORD-2011-0970, by one of the following methods:

    Internet:   HYPERLINK "http://www.regulations.gov/"
http://www.regulations.gov : Follow the on-line instructions for
submitting comments.

    E-mail:   HYPERLINK "mailto:ord.docket@epa.gov" 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   HYPERLINK "mailto:ord.docket@epa.gov"
ord.docket@epa.gov  for instructions. Updates to Public Reading Room
access are available on the Web site (  HYPERLINK
"http://www.epa.gov/epahome/dockets.htm"
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   HYPERLINK "http://www.regulations.gov/"
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   HYPERLINK
"http://www.regulations.gov/" http://www.regulations.gov  or e-mail. The
  HYPERLINK "http://www.regulations.gov/" 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   HYPERLINK "http://www.regulations.gov/"
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:   HYPERLINK
"mailto:downing.jim@epa.gov" downing.jim@epa.gov , or Lu-Ann Kleibacker
at telephone number: (202) 564-7189; fax: 202-564-2070; e-mail address: 
 HYPERLINK "mailto:kleibacker.lu-ann@epa.gov" 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   HYPERLINK "http://www.epa.gov/osa/hsrb/"
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, 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   HYPERLINK
"http://www.regulations.gov/regulations.gov" regulations.gov , you may
access this Federal Register document electronically through the EPA
Internet under the “Federal Register” listings at   HYPERLINK
"http://www.epa.gov/fedrgstr/" http://www.epa.gov/fedrgstr/ .

    Docket: All documents in the docket are listed in the   HYPERLINK
"http://www.regulations.gov/" 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   HYPERLINK
"http://www.regulations.gov/" 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 e-mail the ORD Docket at   HYPERLINK
"mailto:ord.docket@epa.gov" ord.docket@epa.gov  for instructions.
Updates to Public Reading Room access are available on the Web site ( 
HYPERLINK "http://www.epa.gov/epahome/dockets.htm"
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   HYPERLINK
"http://www.regulations.gov/regulations.gov" regulations.gov  Web site
and the EPA HSRB Web site at   HYPERLINK "http://www.epa.gov/osa/hsrb/"
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.

    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 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   HYPERLINK
"http://www.epa.gov/osa/hsrb/" http://www.epa.gov/osa/hsrb/  and  
HYPERLINK "http://www.regulations.gov/" http://www.regulations.gov . In
addition, information concerning a Board meeting report, if applicable,
can be found at   HYPERLINK "http://www.epa.gov/osa/hsrb/"
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

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 [ 
HYPERLINK "http://www.gpo.gov/" 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.

------------------------------------------------------------------------
-------------------------------------------------------

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-ORD-2010-0970:

    Internet:   HYPERLINK "http://www.regulations.gov/"
http://www.regulations.gov : Follow the on-line instructions for
submitting comments.

    E-mail:   HYPERLINK "mailto:ord.docket@epa.gov" 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   HYPERLINK "mailto:ord.docket@epa.gov"
ord.docket@epa.gov  for instructions. Updates to Public Reading Room
access are available on the Web site (  HYPERLINK
"http://www.epa.gov/epahome/dockets.htm"
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   HYPERLINK "http://www.regulations.gov/"
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   HYPERLINK
"http://www.regulations.gov/" http://www.regulations.gov  or e-mail. The
  HYPERLINK "http://www.regulations.gov/" 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   HYPERLINK "http://www.regulations.gov/"
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 EPA-HQ-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

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

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

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