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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

 WASHINGTON D.C., 20460 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION

March 8, 2011 

MEMORANDUM 

SUBJECT: Ethics Review of Completed AHETF Open Cab Airblast Scenario Worker 

Exposure Monitoring Study 

 

FROM: Kelly Sherman 

Human Research Ethics Review Officer 

Office of Pesticide Programs 

TO: Steve Knizner, Associate Director 

Health Effects Division 

REF: Bruce, Eric D. (2010) Determination of Dermal and Inhalation Exposure 

to Workers During Airblast Applications of Liquid Sprays Using Open 

Cab Equipment in California Trellis Crops. Study Number AHE62. 283 

p. (MRID 48289611) [Volume 1]

 Bruce, Eric D. (2010) IIRB Correspondence Report for Cluster Report 

AHE62. 327 p. (MRID 48289614) [Volume 2]

 Bruce, Eric D. (2010) Determination of Dermal and Inhalation Exposure 

to Workers During Airblast Applications of Liquid Sprays Using Open 

Cab Equipment in New York Trellis Crops. Study Number AHE63. 247 

p. (MRID 48289612) [Volume 3]

 Bruce, Eric D. (2010) IIRB Correspondence Report for Cluster Report 

AHE63. 295 p. (MRID 48289615) [Volume 4]

 Bruce, Eric D. (2010) Determination of Dermal and Inhalation Exposure 

to Workers During Airblast Applications of Liquid Sprays Using Open 

Cab Equipment in Oklahoma Tree Nuts. Study Number AHE64. 236 p. 

(MRID 48289613) [Volume 5]
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 Bruce, Eric D. (2010) IIRB Correspondence Report for Cluster Report 

AHE64. 172 p. (MRID 48289616) [Volume 6] 

I have reviewed the available information concerning the ethical conduct of the 

research reported in the referenced documents, which describe the execution and results 

of a series of three field studies in which dermal and inhalation exposure of professional 

pesticide applicators was monitored as they applied liquid pesticides to orchard and trellis 

crops using an airblast sprayer drawn by a tractor with no cab (known as an “open cab”). 

If these studies are determined to be scientifically acceptable, I find no barrier in 

regulation to EPA’s reliance on them in actions under FIFRA or FFDCA. 

1.0 Background and Ethics-related Chronology 

 Three separate field studies were conducted, each monitoring workers while they 

sprayed trellis or tree crops in three different states in the U.S where open cab airblast 

equipment is used in production agriculture. The studies are summarized in Table 1. 

Table 1. Study Summary 

Study 

ID State Crop Number of Monitored Workers Gender Ages 

AHE62 CA Grapes 3 All male 43-79 

AHE63 NY Grapes 5 All male 28-66 

AHE64 OK Pecans 5 All male 47-74 

The background and ethics-related chronology for each field study are summarized 

below. 

1.1 AHE62

The scenario design and protocol for AHE62 were approved by the overseeing 

IRB, the Independent Investigational Review Board, Inc. (IIRB), of Plantation, Florida, 

in July 2008 and submitted to EPA for review in August 2008. The protocol and EPA’s 

review dated September 23, 2008 were discussed by the Human Studies Review Board 

(HSRB) at its October 2008 meeting. The HSRB review was generally favorable, and the 

Board’s December 30, 2008 final report concluded, with respect to ethics, that “[i]f 

revised as suggested by the Board in its review, the research described in these three 

protocols is likely to meet the applicable requirements of 40 CFR part 26, subparts K and 

L.” 

Following the HSRB review, the protocol, consent form, California Experimental 

Research Subject’s Bill of Rights (CaBOR), and recruitment materials for AHE62 were 

revised to address EPA, California Department of Pesticide Regulation (CDPR), and 

HSRB comments. The revised documents were submitted to IIRB in March 2009 and 

approved in April 2009. Three subsequent amendments were approved by IIRB in June, 

July, and November 2009. 
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Subject monitoring for AHE62 took place in July 2009. Three male subjects 

between the ages of 43 and 79 were monitored for dermal and inhalation exposure while 

applying pesticide sprays using open-cab airblast equipment to grapes in California. 

There was one reported deviation during the field phase of the research, and one reported 

deviation during the analytical phase. I noted one unreported deviation. 

A detailed chronology of the ethics-related study activities for AHE62 is provided 

in Table A in Attachment 1. A summary of amendments and reported and unreported 

deviations from all studies is provided in Table 2, on page 11. 

1.2 AHE63

The scenario design and protocol for AHE63 was approved by IIRB in July 2008 

and submitted to EPA for review in August 2008. The protocol and EPA’s review dated 

September 23, 2008 were discussed by the HSRB at its October 2008 meeting. The 

HSRB review was generally favorable, and the Board’s December 30, 2008 final report 

concluded, with respect to ethics, that “[i]f revised as suggested by the Board in its 

review, the research described in these three protocols is likely to meet the applicable 

requirements of 40 CFR part 26, subparts K and L.” 

Following the HSRB review, the protocol, consent form, and recruiting materials 

for AHE63 were revised to address EPA and HSRB comments. The revised documents 

were submitted to IIRB on January 16, 2009, and approved on January 19, 2009. Two 

subsequent amendments were approved by IIRB in July and August 2009. 

Subject monitoring for AHE63 took place in July and August 2009. Five male 

subjects between the ages of 28 and 66 were monitored for dermal and inhalation 

exposure while applying pesticide sprays using open-cab airblast equipment to grapes in 

New York. There was one reported deviation during the field phase of the research, and 

two reported deviations during the analytical phase. I noted no unreported deviations. 

A detailed chronology of the ethics-related study activities for AHE63 is provided 

in Table B in Attachment 1. A summary of amendments and reported and unreported 

deviations from all studies is provided in Table 2, on page 11. 

1.3 AHE64

The scenario design and protocol for AHE64 was approved by IIRB in July 2008 

and submitted to EPA for review in August 2008. The protocol and EPA’s review dated 

September 23, 2008 were discussed by the HSRB at its October 2008 meeting. The 

HSRB review was generally favorable, and the Board’s December 30, 2008 final report 

concluded, with respect to ethics, that “[i]f revised as suggested by the Board in its 

review, the research described in these three protocols is likely to meet the applicable 

requirements of 40 CFR part 26, subparts K and L.” 
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Following the HSRB review, the protocol, consent form, and recruiting materials 

for AHE64 were revised to address EPA and HSRB comments. The revised documents 

were submitted to IIRB on January 16, 2009, and approved on January 19, 2009. Two 

subsequent amendments were approved by IIRB in June and September 2009. 

Subject monitoring for AHE64 took place in August 2009. Five male subjects 

between the ages of 47 and 74 were monitored for dermal and inhalation exposure while 

applying pesticide sprays using open-cab airblast equipment to pecans in Oklahoma. 

There was one reported deviation during the field phase of the research, and one reported 

deviation during the analytical phase. I noted no unreported deviations. 

A detailed chronology of the ethics-related study activities for AHE64 is provided 

in Table C in Attachment 1. A summary of amendments and reported and unreported 

deviations from all studies is provided in Table 2, on page 11.

2.0 Completeness of Submission: 

The checklist used by EPA to verify satisfaction of the requirements of §26.1303 

as they apply to the report of this research appears as Attachment 1 to this review. This 

review considers the 6 study volumes identified on pages 1-2, plus the Heat Index 

Records from the Raw Data (which were provided separately by the AHETF, upon 

request from EPA [via an email from V. Canez to K. Sherman, 3/8/11]). The Heat Index 

records are included as Attachment 4 to this review. 

3.0 Protocol Amendments: 

3.1 AHE62

Following EPA’s and HSRB’s reviews, the protocol, consent form, and recruiting 

materials were revised to address EPA, HSRB, and CDPR comments. The revised 

materials were submitted to IIRB on March 27, 2009, and approved on April 1 and 6, 

2008. 

In early June 2009, the AHETF consulted EPA about three changes to the AHE62 

protocol, and EPA ultimately approved the changes. On June 19, 2009, the AHETF 

submitted to IIRB an amendment encompassing the three changes, and IIRB approved 

the amendment on June 23, 2009. Each of the three changes is discussed below. 

1) The first change was to amend the inclusion criteria to allow participation by 

individuals who normally wear two layers of clothing (the inclusion criteria 

previously stated that only workers who normally wear one layer of clothing 

would be eligible to participate). The change was in response to a discovery 

by the AHETF that many airblast applicators in Fresno County normally wear 

two layers of clothing (for example, a typical shirt and pants under a cloth 
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coverall). To accommodate these workers and increase the pool of potentially 

eligible workers, the AHETF sought to amend the inclusion criteria. EPA 

approved the change provided that the workers who normally wear two layers 

agree to substitute their normally-worn inner layer of clothing for the long 

underwear dosimeter provided by the AHETF. The change was acceptable to 

EPA from an ethics perspective because it neither requires participants to 

wear less clothing than they normally would, nor results in subjects wearing a 

third layer of clothing, which could increase the risks of heat-related illness. 

2) The second change was to expand the permissible recruitment area to any 

county in California or Washington if the county previously specified in the 

protocol (Fresno County, California) does not provide a sufficient number of 

eligible growers. The change appeared to be necessary because many 

potential subjects in Fresno County might not be eligible to participate 

because they normally wear Tyvek coveralls, or because their Pest Control 

Advisor, winery, or raisin packer might not approve the use of either of the 

two surrogate compounds. 

3) The third change was to remove the efficient configuration requirement if the 

recruitment area is expanded. 

On July 22, 2009, the AHETF submitted an additional amendment to IIRB to add 

to the list of approved test substances a malathion end-use product preferred by some 

growers. EPA approved the addition of this product to the list of possible surrogates, and 

IIRB approved the amendment on July 22, 2009. 

In November 2009, the AHETF submitted an amendment to specify the analytical 

methods to be used for head patches; IIRB approved the amendment on November 24, 

2009. 

In EPA’s view, the amendments to AHE62 are not problematic from an ethics 

perspective because they do not increase risks to subjects or jeopardize informed consent. 

I defer to the EPA science reviewer about whether these amendments are important from 

a science perspective. 

3.2 AHE63

Following EPA’s and HSRB’s reviews, the protocol, consent form, and recruiting 

materials were revised to address EPA and HSRB comments. The revised materials were 

submitted to IIRB on January 16, 2009, and approved on January 19, 2009. 

On June 26, 2009, the AHETF submitted to IIRB two proposed recruitment letters 

that would be sent to grape growers in New York State before the initial recruiting 

telephone calls. The letters were approved by IIRB on the same day that they were 

submitted. 
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On July 17, 2009, the AHETF submitted to IIRB an amendment encompassing 

the changes listed below. IIRB approved the amendment on July 21, 2009. 

1) The first change was a modification to the recruitment process to allow for use 

of the two recruitment letters that were approved by IIRB on June 26, 2009. 

In EPA’s view, adding this new step to the recruitment process does not raise 

ethics concerns because (a) researchers intend to send one of the two letters to 

all of the grape growers whose names appear on the master list of New York 

grape growers; (b) the letters have been IRB-approved; and (c) the letters may 

help to increase the number of growers who are willing to take part in an 

initial recruitment telephone conversation. 

2) The second change was to reduce the heat index threshold for stopping the 

research from 120° F to 105° F. The change was made, in part, to address 

concerns from the HSRB that the previous heat index threshold of 120° F was 

too high. EPA supports this change because it increases protection for 

subjects. 

3) The third change was to revise the dermal exposure sampling procedure to 

specify that the inner dosimeters would be cut into 6 sections after collection 

rather than 2 sections. Analyzing the dosimeters in more sections allows the 

AHETF to determine body-specific residues for more body parts, which may 

be important because this exposure scenario is expected to result in relatively 

high dermal exposure potential. It may be useful have to ability to more 

precisely pinpoint the areas of highest exposure. This change does not impact 

any ethics considerations. 

4) The fourth change was to revise the analytical methods to make them more 

appropriate for whole-body dosimeters sectioned into 6 pieces. This change 

does not impact any ethics considerations. 

5) The fifth change was to clarify in the protocol the AHETF’s raw data 

retention policy. The following sentence was added to the protocol: 

“In accordance with GLP regulations (40 CFR 160.195) and SOP 

AHETF-6.A, raw data will be retained in archives as long as the AHETF 

or other registrant holds a research or marketing permit to which the study 

is pertinent.” 

 This change does not impact any ethics considerations. 

In EPA’s view, the five changes encompassed in this amendment are not 

problematic from an ethics perspective because they do not increase risks to subjects or 

jeopardize informed consent, and they were approved by IIRB before implementation. I 

defer to the EPA science reviewer about whether these changes are important from a 

science perspective. 
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The AHETF submitted an additional protocol amendment to IIRB on August 13, 

2009, changing the procedures for chemical analysis of the head patches. This 

amendment does not affect any ethics considerations, but I defer to the EPA science 

reviewer about whether this amendment is important from a science perspective. 

3.3 AHE64

Following EPA’s and HSRB’s reviews, the protocol, consent form, and recruiting 

materials were revised to address EPA and HSRB comments. The revised materials were 

submitted to IIRB on January 16, 2009, and approved on January 19, 2009. 

On June 15, 2009, the AHETF submitted to IIRB two proposed recruitment letters 

that would be sent to Oklahoma pecan growers before the initial recruiting telephone 

calls, plus an amendment encompassing the changes discussed below. IIRB approved the 

letters and the amendment on June 19, 2009. 

1) The first change was a modification to the recruitment process to allow for use 

of the two recruitment letters which were submitted in conjunction with the 

amendment. In EPA’s view, adding this new step to the recruitment process 

does not raise ethics concerns because (a) researchers intend to send one of 

the two letters to all of the pecan growers whose names appear on the master 

list of Oklahoma pecan growers; (b) the letters have been IRB-approved; and 

(c) the letters may help to increase the number of growers who are willing to 

take part in an initial recruitment telephone conversation. 

2) The second change was to expand the permissible recruitment area from Tulsa 

County, Oklahoma, to also include the adjacent Oklahoma counties of Creek, 

Okmulgee, Wagoner, Rogers, Washington, and Osage. The reason for the 

change was that obtaining a list of nut growers in Oklahoma was proving 

difficult, and indications were that open cabs are less prevalent than closed 

cabs in Oklahoma. Only pecan grower names could be obtained, but this 

represents the majority of nut crops in Oklahoma. The U.S. Census of 

Agriculture indicates there are 95 growers of pecans in Tulsa County that 

grow the minimum necessary acreage (at least 5 acres). Based on response 

rates from other studies, the AHETF observed that a list of 95 growers was 

likely too small to yield 5 potentially eligible growers. Expanding the 

recruitment area to include the surrounding counties results in a list of 279 

growers which should provide a sufficient number of potentially eligible 

growers. In EPA’s view, this change is not problematic from an ethics 

perspective because it does not increase risks to subjects or jeopardize 

informed consent. I defer to the EPA science reviewer about whether this 

change is important from a science perspective. 

3) The third change was to remove the efficient configuration requirement if the 

recruitment area is expanded. 
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4) The fourth change was to revise the dermal exposure sampling procedure to 

specify that the inner dosimeters would be cut into 6 sections after collection 

rather than 2 sections. Analyzing the dosimeters in more sections allows the 

AHETF to determine body-specific residues for more body parts, which may 

be important because this exposure scenario is expected to result in relatively 

high dermal exposure potential. It may be useful have to ability to more 

precisely pinpoint the areas of highest exposure. This change does not impact 

any ethics considerations. 

5) The fifth change was to revise the analytical methods to make them more 

appropriate for whole-body dosimeters sectioned into 6 pieces. This change 

does not impact any ethics considerations. 

On September 14, 2009, the AHETF submitted to IIRB a second protocol 

amendment, changing the study director from Eric D. Bruce to Larry D. Smith. The 

effective date for the change in study director was September 14, 2009, after the close of 

the study. This amendment does not affect any ethics considerations. IIRB approved the 

amendment on September 16, 2009. 

4.0 Protocol Deviations: 

4.1 AHE62

 

 4.1.1 Reported Deviations

There was one reported deviation during the field phase of AHE62. Inner and 

outer head patch field fortifications were performed in duplicate rather than in triplicate. 

In addition, no samples were taken for the higher fortification level (100 ug) for the inner 

head patches. The deviation occurred because a researcher initially fortified head patch 

matrices in a way that was not in accordance with the relevant SOP (AHE-8.E.5). The 

error was discovered while still in the field, so correct matrices were fortified. However, 

there were only enough extra fortification vials remaining for duplicate samples and there 

were no vials available for the 100 ug high fortification rate for inner head patches. This 

deviation occurred on July 2, 2009, and was reported to IIRB on September 2, 2009. On 

September 3rd, IIRB acknowledged the deviation and concluded that it did not place 

subjects at increased risk. In EPA’s view, this deviation is not significant from an ethics 

perspective. I defer to the EPA science reviewer about whether this deviation is 

important from a science perspective. 

There was one reported deviation in the analytical phase of the research. Field 

fortification solutions for some lots were not verified to establish concentration. This 

deviation raises no ethical issues, but I defer to the EPA science reviewer on whether it 

affects the scientific integrity of the data. 
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4.1.2 Unreported Deviations

I noted one unreported deviation during the field phase of AHE62. Subject A2 

was monitored for only 174 minutes, although the protocol requires a minimum 4-hour 

monitoring period. This deviation raises no ethical issues, but I defer to the EPA science 

reviewer on whether it affects the scientific integrity of the data. 

4.2 AHE63

 

 4.2.1 Reported Deviations

There were two reported deviations during the field phase of AHE63. One 

subject (A5) applied only 2 tank loads of spray mixture and sprayed for only 2 hours, 

although the protocol specifies “Each MU shall consist of a period of at least 4 hours of 

spraying and at least 3 tank loads of the spray mixture.” The deviation occurred because 

the pesticide needed to be applied at a specific concentration in order to achieve efficacy. 

It was not possible to increase the spray volume or reduce the tractor ground speed to 

reach the protocol-required targets without sacrificing efficacy. 

The second deviation was that the highest stratum (56 to 100 lbs active 

ingredient) was not filled; the highest amount of active ingredient sprayed by a subject in 

this study was 48 lbs. This deviation occurred because New York grape applicators 

typically apply at a rate of 32 lbs active ingredient per day, and thus could not achieve the 

amount in stratum 5 without working an abnormally long day. Both of the deviations 

occurred between July 28 and August 6, 2009, and were reported to IIRB on September 

11, 2009. On September 15th, IIRB acknowledged the deviation and concluded that it 

did not place subjects at increased risk. The deviation does not raise ethical issues 

because the expected exposure as a result of this deviation is not out of the range of safe 

exposures based on pre-study evaluations of risk. I defer to the EPA science reviewer 

about whether this deviation is important from a science perspective. 

 

There also were two method deviations related to analysis of carbaryl in inner 

dosimeters and face/neck wipe samples that were reported to IIRB. These analytical 

deviations raise no ethical issues, but I defer to the EPA science reviewer on whether they 

affects the scientific integrity of the data. 

4.2.2 Unreported Deviations

 

I noted no unreported deviations during the field phase of AHE63. 
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4.3 AHE64

 

 4.3.1 Reported Deviations

There was one reported deviation during the field phase of AHE64 that involved 

departures from the protocol-required minimum application time, number of spray loads, 

and active ingredient strata. Four of the five subjects (A2, A3, A4, and A5) each sprayed 

only 2 tank loads of spray mixture for less than 4 hours each, contrary to the protocol 

requirement that subjects should be monitored for a minimum of 4 hours and apply at 

least 3 tank loads. In addition, the lowest stratum (5 to 9 lbs active ingredient) was not 

achieved by any of the subjects. The reason given for the deviation was that highest label 

rate was required for controlling the target pest. It was not possible to increase the spray 

volume or reduce the tractor ground speed and still achieve efficacy. Application times 

were dictated by the grower spray patterns and orchard configurations. The deviation 

occurred between August 22-29, 2009, and was reported to IIRB on September 18, 2009. 

On September 23, 2009, IIRB acknowledged the deviation and indicated that no 

additional action was required. The deviation does not raise ethical issues because the 

expected exposure as a result of this deviation is not out of the range of safe exposures 

based on pre-study evaluations of risk. I defer to the EPA science reviewer on whether 

this deviation raises science issues. 

There also was one method deviation in the analytical phase, related to analysis of 

carbaryl in inner dosimeters, reported to IIRB. This deviation raises no ethical issues, but 

I defer to the EPA science reviewer on whether it affects the scientific integrity of the 

data. 

4.3.2 Unreported Deviations

I noted no unreported deviations during the field phase of AHE64. 

 
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Table 2. Summary of Protocol Amendments and Deviations 

Study 

ID Amendments Deviations 

Field Phase Analytical Phase 

AHE62 

1. Amended to incorporate comments from EPA, 

California Department of Pesticide Regulation, 

and HSRB. 

Reported: 

1. On study day 1, inner and 

outer head patch field 

fortifications were 

conducted in duplicate 

instead of triplicate, and on 

study day 1, no samples 

were taken for the higher 

fortification level (100 ug) 

for the inner head patches. 

Unreported: 

1. Subject A2 was monitored 

for 174 minutes, although 

the protocol requires a 

minimum 4-hour period. 

1. Field 

fortification 

solutions for 

some lots 

were not 

verified to 

establish 

concentration 

2. Protocol Amendment 1 

• Inclusion criteria amended to allow 

participation of workers who normally 

wear two layers of clothing. 

• Recruitment area expanded to allow any 

county in CA or WA. 

• Removed efficient configuration 

requirement if recruitment area is 

expanded. 

3. Protocol Amendment 2 

• Added a new malathion product to possible 

test products (the active ingredient 

malathion was already an approved 

surrogate) 

4. Protocol Amendment 3 

• Specified the analytical methods to be used 

for head patches 

AHE63 

1. Amended to incorporate comments from EPA 

and HSRB. 

Reported: 

1. Subject A5 applied only 2 

tank loads and sprayed for 

only 2 hours, although the 

protocol specifies that each 

subject should apply a 

minimum of 3 tank loads 

over a minimum time of 4 

hours; also, the highest 

stratum (56 to 100 lbs a.i.) 

was not achieved; the 

highest amount sprayed was 

48 lbs a.i. 

Unreported: 

1. None 

1. The analytical 

laboratory 

deviated from 

methodologies 

related to 

analysis of 

carbaryl in 

inner 

dosimeters 

2. The analytical 

lab deviated 

from 

methodologies 

related to 

analysis of 

carbaryl in 

face/neck 

wipe samples 

2. Protocol Amendment 1 

• Recruitment process modified to permit 

use of recruitment letters 

• Reduce heat index stopping rule from 120° 

F to 105° F 

• Amend dermal exposure sampling 

procedure to specify that the inner 

dosimeters would be cut into 6 sections 

rather than 2 sections 

• Revise analytical methods to make them 

appropriate for dosimeters cut into 6 pieces 

• Amend protocol to clarify the AHETF’s 

raw data retention policy 

3. Protocol Amendment 2 

• Amended analytical method for head 

patches 

AHE64 

• Amended to incorporate comments from EPA 

and HSRB. 

Reported: 

1. Subjects A2, A3, A4, A5 

each applied only 2 tank 

loads and sprayed for less 

than 4 hours, although the 

protocol specifies that each 

subject should apply a 

minimum of 3 tank loads 

over a minimum time of 4 

hours. Also, the lowest 

stratum (5 to 9 lbs a.i.) was 

not achieved; the lowest 

amount sprayed was 10 lbs 

a.i. 

Unreported: 

1. None 

1. The analytical 

laboratory 

deviated from 

analytical 

methodologies 

related to 

analysis of 

carbaryl in 

inner 

dosimeters 

• Protocol Amendment 1 

• Recruitment process modified to permit 

use of recruitment letters 

• Recruitment area expanded to allow 

counties adjacent to Tulsa County, OK. 

• Removed efficient configuration 

requirement if recruitment area expanded. 

• Amended dermal exposure sampling 

procedure to specify that the inner 

dosimeters would be cut into 6 sections 

• Revise analytical methods to make 

appropriate for dosimeters cut in 6 sections 

3. Protocol Amendment 2

• The study director was changed from Eric 

D. Bruce to Larry D. Smith, effective 

September 14, 2009 (after study closure) 
Page 12 of 51 

5.0 Recruiting 

The three-phase recruiting process outlined in the protocol and SOPs AHETF11.K.O, 11.L.0, and 11.M.0 appears to have been followed in all three studies. An initial 

grower universe list was generated from published lists or databases. Duplicate entries 

and growers with missing phone numbers were suppressed, to produce the master grower 

lists (which ranged in size from 330 names to 4,064 names in the three studies). After 

protocols were finalized and signed by the study director, qualifying calls were placed to 

the names on the master grower list, and the lists were narrowed by eliminating names 

based on responses to qualifying questions, being unreachable, or lack of interest in 

participating in the research. The resulting lists contained names of growers who were 

qualified and interested in participating in the research. For the final stage of recruiting, 

the study director contacted and/or visited all qualified growers, to identify growers who 

could participate in a timeframe and schedule to allow the study to be conducted 

efficiently. Table 2 in each of the Study Reports (Volume 1, p. 38; Volume 3, p. 32; 

Volume 5, p. 33) details the number of growers/workers in each stage of the recruitment 

process. 

The AHETF encountered difficulties recruiting growers for AHE62. This study 

required open cab airblast equipment and bush trellis crops in commercial production. In 

the initial phase of recruiting, lists of growers of grapes, blackberries, blueberries, 

boysenberries, loganberries, and raspberries were generated. Because less than 0.3% of 

the growers grew a trellis crop other than grapes, and none of the “other bush crop” 

growers qualified for inclusion in the study, the remainder of the recruitment efforts were 

directed toward grape growers. Recruitment initially focused on Fresno, California, but 

the many of the qualified handlers in Fresno wore additional personal protective 

equipment (PPE) (for example, coveralls or rain suits) or did not want to use the 

surrogate chemicals listed in the protocol, and therefore could not be recruited. Due to 

these difficulties, the protocol was amended to allow recruitment from all counties in 

California and Washington (see discussion of the protocol amendment in section 3.1of 

this review). The early-phase recruitment efforts resulted in a master grower list 

containing 4,064 names. The relatively large master grower list yielded a small qualified 

grower list (259 names), however, because a great majority of the growers who were 

contacted were not qualified because they wore chemical-resistant PPE, grew less than 10 

acres, did not use open cab equipment, refused the interview, or were not able to be 

contacted. Ultimately, the 259 names on the qualified grower list only yielded 4 growers 

on the eligible grower list because many of the growers were either unwilling to 

participate or unable to use either of the planned surrogates. Three of the 4 eligible 

growers were ultimately monitored in AHE62. The fourth grower did not participate 

because his Pest Control Advisor did not approve use of either of the AHETF surrogates, 

and instead recommended a different pesticide. 

5.1 Subject Representativeness

 At the conclusion of the field phase of each of the studies, the AHETF conducted 

a survey of area experts to evaluate the representativeness of the growers/applicators 
Page 13 of 51 

participating in the study. These surveys were responsive to the HSRB’s request that the 

AHETF attempt to characterize whether the monitored workers were typical of that type 

of worker/grower in the particular region. 

For AHE62, four out of five area experts that responded to the survey opined that 

the growers/applicators were typical. The fifth local farm expert, who was from San 

Joaquin County, commented that the study acreage seemed to be smaller than would be 

typical for San Joaquin County. He also speculated that the study acreage seemed to be 

larger than would be typical for Fresno County, although he said that he said that he is 

not very familiar with Fresno. He said that he thought the acreage was typical for El 

Dorado County. 

For AHE63, three of the four local farm experts who responded to the survey 

agreed that the study participants were typical of local grape growers/applicators in the 

county where the study cluster was performed. The fourth expert said that the types of 

airblast sprayers used in the study were not entirely representative since the Kinkelder 

airblast sprayer, an older model sprayer that is more prone to producing drift, was not 

included in the study. 

For AHE64, four out of the seven local farm experts who responded to the survey 

agreed that the study participants were typical of local pecan growers/applicators in the 

counties where the study cluster was performed. Of the three experts who did not agree 

that the study participants were typical, one indicated that a typical grower would have 

larger acreage than the pecan groves encountered in this study. The other two experts 

opined that the pecan growers in the study were not typical because most pecan growers 

in the area use closed cabs, not open cabs. 

6.0 Consent Process 

The consent process outlined in the protocols and SOPs was closely followed in 

all studies. There were no reported deviations related to the consent process, and I did 

not note any unreported deviations related to consent during my review of the study 

reports. Twelve of the 13 subjects completed the consent process in English, and none of 

the subjects used a witness. 

7.0 Subject Demographics 

Demographic information on the monitored subjects is summarized in Table 3 

below. 

 
Page 14 of 51 

Table 3: Subject Characteristics 

Number of Subjects 

AHE62 AHE63 AHE64 

Males 3 5 5 

Females 0 0 0 

Completed consent process in English 2 5 5 

Completed consent process in Spanish 1 0 0 

Self-identified as non-reader and used witness 0 0 0 

Employment 

 Farm Owner or Operator 2 5 5 

 Farm Employee 1 0 0 

 Commercial Applicator 0 0 0 

Years of Experience 8-30 4-39 3-40 

Age Range 43-79 28-66 47-74 

Requested Results 3 5 5 

Withdrew 0 0 0 

Removed from participation by AHETF 0 0 0 

7.1 Health Status

Prospective subjects were asked about their health status during the consent 

process, using the procedures described in SOPs AHETF-11.B.4 and AHETF-11.C.1. No 

prospective subjects were eliminated due reported health status. The inclusion criteria in 

the protocol state that subjects must report “good general health with no medical 

conditions that could impact their ability to participate in the study” in order to be eligible 

to participate (protocol section 2.1). 

8.0 Monitoring 

Exposure monitoring was conducted without incident. No subjects withdrew 

from the research. No adverse events or other incidents of concern were reported. 

8.1 Heat Index

 

The greatest risk to subjects in this research is that of heat-related illness. The 

SOP titled “Identification and Control of Heat Stress” (AHETF-11.G.1) provides 

information about recognition of conditions that contribute to heat-related illness, 

measures to minimize the risk of heat-related illness, measures to be taken if a worker is 

affected by heat-related illness, procedures for AHETF researchers to monitor 

environmental conditions, and stopping rules related to heat-related illness. The version 

of the SOP that was in place at the time that these three field studies were conducted 

(AHETF-11.G.1) provided that the research should not begin, or should be halted, if the 

ambient heat index (temperature adjusted for humidity and direct sunlight) was greater 

than or equal to 120° F. In November 2009 (after this research was completed), the SOP 

was revised to lower the heat index threshold from 120° F to 105° F (revised version is 

AHETF-11.G.2). 
Page 15 of 51 

 Although the SOP in effect at the time of the research specified a heat index 

threshold of 120° F, the protocols for AHE62 and 63 were amended to lower the heat 

index threshold to 105° F. The protocol for AHE64 was not revised in the same manner 

– the heat index threshold for AHE64 remained at 120° F. 

 Table 4, below, provides the maximum heat index measurements in AHE62, 63, 

and 64. None of the measured heat index values exceeded the cut-off values of 105° F or 

120° F. 

Table 4. Heat Index Values (°F)

Study 

ID 

A1 A2 A3 

Time Heat 

Index Time Heat Index Time Heat Index 

AHE62 

0723 <80 0622 <80 0742 <80 

0816 <80 0651 <80 0814 <80 

0901 <80 0720 <80 0910 91 

1001 <80 0810 <80 0958 93 

1112 83 0835 <80 1038 93 

 1126 95 

AHE63 

A1* A2 A3 A4 A5 

0820 <80 1000 <80 1000 <80 

Ambient 

temperature did 

not reach 70 °F 

Ambient 

temperature did 

not reach 70 °F 

0920 <80 1100 <80 1100 <80 

1020 <80 1200 <80 1200 <80 

1120 <80 1300 <80 1300 <80 

1220 95 

1320 98 

1420 85 

1520 98 

1620 88 

1720 94 

1820 95 

AHE64 

A1* A2 A3 A4 A5 

1003 <80 0930 <80 1100 88 0850 <80 0834 <80 

1102 92 1026 81 1200 91 0950 <80 0930 <80 

1201 82 1300 94 1052 <80 1030 <80 

1301 82 

1401 83 

* The heat index values for fluctuated due to passing periods of cloudiness. 

“Caution” = heat index between 80-89°F 

“Extreme caution” = heat index between 90-104°F 

 8.1.1 AHE62

When subject A1 was monitored, the heat index rose into the “caution” range 

(heat index between 80-89° F; see SOP AHETF-11.G.1). As documented in Supplement 

1 and reported in the worker observation log for subject A1 (p. 45, Volume 2), the study 

director announced the “caution” heat index at 11:12 am, in compliance with SOP 

AHETF-11.G.1. Eight minutes later (11:20 am), the log states that the subject 

“confirmed he still felt fine.” The spraying was complete at that point, and the log 
Page 16 of 51 

reports that at 11:21 am, the subject rode to the staging area in the Study Director’s 

vehicle. 

When subject A3 was monitored, the heat index rose into the “Extreme Caution” 

category. According to the raw data report (see Supplement 1), the observer was also the 

weather monitor, so separate notification of the observer was not necessary. It does not 

appear that the worker was in danger of suffering heat illness at any point during the 

study. The log shows that the worker talked to the nurse and drank Gatorade at 8:02 am, 

resumed spraying at 8:18 am, and “checked with nurse” at 11:10 am, saying that he “feels 

ok” (p. 47-49, Volume 2). 

 8.1.2 AHE63

 When subject A1 was monitored, the heat index rose into the “Caution” and 

“Extreme Caution” categories. According to the raw data report (see Supplement 1), the 

person responsible for monitoring the weather notified the observer of the heat index 

category changes, in compliance with SOP AHETF-11.G.1. It does not appear that the 

worker was in danger of suffering heat illness at any point during the study. The worker 

observation log shows that the worker got a drink and “stated he was fine” at 10:11; took 

a break and had lunch between 11:10 and 12:11; drank water and “stated he was feeling 

fine” at 13:35; had more to drink and “stated he is feeling fine” at 15:09; “stated he was 

feeling fine” at 16:15; and had a drink at 17:37 (p. 40-41, Volume 4). 

 

 8.1.3 AHE64

 When subject A1 was monitored, the heat index rose into the “Caution” and 

“Extreme Caution” categories. According to the raw data report (see Supplement 1), the 

person responsible for monitoring the weather notified the observer of the heat index 

category changes, in compliance with SOP AHETF-11.G.1. It does not appear that the 

worker was in danger of suffering heat illness at any point during the study. The worker 

observation log shows that the worker had a drink at 07:43; “stated he was feeling fine” 

at 09:27; took a break for lunch between 12:11 and 13:11. (p. 39-40, Vol. 6). 

When subject A2 was monitored, the heat index rose into the “Caution” range. 

According to the raw data report (see Supplement 1), the person responsible for 

monitoring the weather notified the observer and researchers of the heat index category 

changes, in compliance with SOP AHETF-11.G.1. It does not appear that the worker was 

in danger of suffering heat illness at any point during the study. 

When subject A3 was monitored, the heat index rose into the “Caution” and 

“Extreme Caution” categories. According to the raw data report (see Supplement 1), the 

person responsible for monitoring the weather notified the observer and researchers of the 

heat index category changes, in compliance with SOP AHETF-11.G.1. It does not appear 

that the worker was in danger of suffering heat illness at any point during the study. The 

worker observation log shows that the worker had a drink at 10:11 am. (p. 42, Volume 6). 
Page 17 of 51 

9.0 Applicable Ethical Standards 

The following provisions of 40 CFR 26 Subpart Q, as amended effective August 

22, 2006, define the applicable ethical standards, which read in pertinent part: 

§26.1703: Except as provided in §26.1706, . . . EPA shall not rely on data 

from any research involving intentional exposure of any human subject 

who is a pregnant woman (and therefore her fetus), a nursing woman, or a 

child. 

§26.1705: Except as provided in §26.1706, . . . EPA shall not rely on data 

from any research initiated after April 7, 2006, unless EPA has adequate 

information to determine that the research was conducted in substantial 

compliance with subparts A through L of this part. . . . 

In addition, §12(a)(2)(P) of the Federal Insecticide, Fungicide and Rodenticide 

Act (FIFRA) applies. This passage reads: 

In general, [i]t shall be unlawful for any person . . . to use any pesticide in 

tests on human beings unless such human beings (i) are fully informed of 

the nature and purposes of the test and of any physical and mental health 

consequences which are reasonably foreseeable therefrom, and (ii) freely 

volunteer to participate in the test. 

10.0 Findings 

10.1 Responsiveness to EPA and HSRB reviews

EPA’s and HSRB’s comments on these protocols were satisfactorily addressed 

before the research was conducted. Please see Attachment 3 for details. 

10.2 Prohibition of research involving intentional exposure of pregnant or 

nursing women or of children 

All enrolled subjects were at least 18 years old and there were no female subjects. 

The prohibition in 40 CFR §26.1703 of research involving intentional exposure of 

pregnant or nursing women or of children under 18 was satisfied. 

10.3 Substantial compliance with 40 CFR 26 subparts A through L 

40 CFR §26.1705 requires that EPA have “adequate information to determine that 

the research was conducted in substantial compliance with subparts A through L of this 

part.” Within this range, only subparts K and L are directly applicable to the conduct of 

third-party research such as this. The study reports for AHE62, AHE63, and AHE64 

document compliance with subparts K and L. 
Page 18 of 51 

10.4 Compliance with 40 CFR §26 subpart M 

As is documented in Attachment 2 to this review, the central requirements of 40 

CFR §26 subpart M, §26.1303 to document the ethical conduct of the research were 

satisfactorily addressed. 

10.5 Compliance with FIFRA §12(a)(2)(P) 

The requirement of FIFRA §12(a)(2)(P) that human subjects of research be “fully 

informed of the nature and purposes of the test and of any physical and mental health 

consequences reasonably foreseeable therefrom,” and “freely volunteer to participate in 

the test,” was met for this study. 

11.0 Conclusion 

This study reports research conducted in substantial compliance with the 

requirements of 40 CFR 26 subparts A through L. In its conduct it met all applicable 

ethical standards for the protection of human subjects of research, and all requirements 

for documentation of ethical conduct of the research were satisfied. If this study is 

determined to be scientifically valid and relevant, there is no regulatory barrier to EPA’s 

reliance on it in actions under FIFRA or §408 of FFDCA. 

Attachment 1: Ethics-related study chronologies (Tables A-C) 

Attachment 2: §26.1303 completeness checks 

Attachment 3: Responsiveness to EPA and HSRB Comments on protocols (Table D) 

Attachment 4: Heat Index Records from Raw Data for AHE62, AHE63, AHE64
Attachment 1 

Ethics-Related Study Chronologies 

Page 19 of 51 

Table A: AHE62 

Date 

10/21-22/08 HSRB reviewed protocol and approved with recommendations 

3/27/09 Submitted documents to IIRB to amend protocol, consent form, and product risk 

statements (following October 2008 HSRB meeting) 

4/1/09 & 4/6/09 IIRB approves revised documents 

4/20/09 Protocol finalized and signed by Study Director 

4/21/09 Phase 1 recruiting (creation of grower list). 4/21/09 to 7/27/09 

5/12/09 Phase 2 recruiting (calls to grower list). 5/12/09 to 8/14/09 

6/01/09 Phase 3 recruiting (site visits and participant selection) - 6/01/09 to 8/14/09 

6/19/09 Submission to IIRB of Protocol Amendment 1 to include workers normally wearing 2 

cloth layers and expand recruitment area 

6/23/09 Approval of Protocol Amendment 1 by IIRB 

7/02/09, 7/20/09 Two subjects monitored (MUs A1, A2) 

7/16/09 Submission of annual progress report to IIRB 

7/22/09 Submission to IIRB of Protocol Amendment 2 adding an additional malathion 

product 

7/22/09 Approval of Protocol Amendment 2 by IIRB 

7/24/09 Third subject monitored (MU A3) 

7/25/09 Submission of supplemental information for Progress Report to IIRB 

7/29/09 Approval by IIRB of ongoing research (i.e., extension granted) 

9/02/09 Protocol Deviation 1 reported to IIRB

• Deviation occurred 7/02/09 

• Inner and outer head patch fortification deficiencies 

9/03/09 IIRB acknowledges Protocol Deviation 1; no further action required 

11/21/09 Submission to IIRB of Protocol Amendment 3 specifying the analytical method and 

LOQ for head patches 

11/24/09 Approval of Protocol Amendment 3 by IIRB 

02/23/10 Close out report submitted to IIRB 

02/25/10 IIRB accepts Study Completion Report; study considered closed 

4/19/10 Laboratory Deviation reported to IIRB

• Deviation occurred 6/05/09 

• Field fortification solution concentration not verified 

4/20/10 IIRB acknowledges Laboratory Deviation; no further action required 

 
Attachment 1 

Ethics-Related Study Chronologies 

Page 20 of 51 

Table B: AHE63 

Date 

10/21-22/08 HSRB reviewed protocol and approved with recommendations 

1/16/09 Submitted documents to IIRB to amend protocol, consent form, and product risk 

statements (following October 2008 HSRB meeting) 

1/19/09 IIRB approves revised documents 

1/23/09 Protocol finalized and signed by Study Director 

6/09/09 Phase 1 recruiting (creation of Master Grower List and Qualified Grower List). 6/9/09 

to 7/17/09 

6/26/09 Grower letters submitted to and approved by IIRB 

7/10/09 Phase 2 recruiting (calls to Qualified Grower List). 7/10/09 to 7/27/09 

7/15/09 Phase 3 recruiting (site visits and participant selection) - 7/15/09 to 8/5/09 

7/16/09 Annual progress report submitted to IIRB 

7/18/09 Submission to IIRB of Protocol Amendment 1 to allow use of recruitment letters, 

lower the heat index threshold from 120° F to 105° F, change dermal sampling 

procedure (dosimeter cut into 6 sections, not 2), and clarify raw data retention policy 

7/21/09 Approval of Protocol Amendment 1 by IIRB 

7/28/09 - 8/06/09 Five subjects monitored (MUs A1, A2, A4, A4, A5) 

7/29/09 IIRB approves ongoing research and annual progress report (submitted on 7/16/09) 

8/13/09 Submission to IIRB of Protocol Amendment 2 providing changes in analytical 

procedures 

8/13/09 Approval of Protocol Amendment 2 by IIRB 

9/11/09 Protocol Deviation 1 reported to IIRB

• Deviations occurred 7/28/09-8/06/09 

• Involved departures from minimum spray time and spray load requirements; 

highest stratum not achieved 

9/15/09 IIRB acknowledges Protocol Deviation 1; no further action required 

7/06/10 2 analytical deviations reported to IIRB

• Deviations occurred 8/19/09, 4/20/10 

• Deviations from analytical methodologies related to analysis of carbaryl in inner 

dosimeters and face/neck wipe samples 

7/09/10 IIRB acknowledges 2 analytical deviations; no further action required 

07/15/10 Close out report submitted to IIRB 

07/20/10 IIRB accepts Study Completion Report; study considered closed 

 
Attachment 1 

Ethics-Related Study Chronologies 

Page 21 of 51 

Table C: AHE64 

Date 

10/21-22/08 HSRB reviewed protocol and approved with recommendations 

1/16/09 Submitted documents to IIRB to amend protocol, consent form, and product risk 

statements (following October 2008 HSRB meeting) 

1/19/09 IIRB approves revised documents 

1/23/09 Protocol finalized and signed by Study Director 

3/02/09 Phase 1 recruiting (creation of Master Grower List and Qualified Grower List). 3/2/09 

to 7/29/09 

6/15/09 Submission to IIRB of Protocol Amendment 1 to allow use of recruitment letters, 

expand grower search area, and change dermal sampling procedure (dosimeter cut into 

6 sections, not 2) 

6/19/09 Approval of Protocol Amendment 1 by IIRB 

7/07/09 Calls to growers on Master Grower List. 7/07/09 to 7/28/09 

7/16/09 Phase 2 recruiting (calls to Qualified Grower List). 7/16/09 to 8/16/09 

7/16/09 Annual progress report submitted to IIRB 

8/04/09 IIRB approves ongoing research and annual progress report (submitted on 7/16/09) 

8/10/09 Phase 3 recruiting (site visits and participant selection) - 8/10/09 to 8/24/09 

8/22/09 - 8/29/09 Five subjects monitored (MUs A1, A2, A4, A4, A5) 

9/14/09 Submission to IIRB of Protocol Amendment 2 changing study director and Change in 

Principal Investigator Form 

9/16/09 Approval of Protocol Amendment 2 by IIRB 

9/18/09 Protocol Deviation 1 reported to IIRB

• Deviations occurred 8/22/09 - 8/29/09 

• Involved departures from minimum spray time and spray load requirements; 

lowest stratum not achieved 

9/23/09 IIRB acknowledges Protocol Deviation 1; no further action required 

7/10/10 Analytical deviation reported to IIRB

• Deviation occurred 5/4/10 

• Deviation from analytical methodologies related to analysis of carbaryl in inner 

dosimeters 

7/13/10 IIRB acknowledges analytical deviation; no further action required 

07/22/10 Close out report submitted to IIRB 

07/23/10 IIRB accepts Study Completion Report; study considered closed 
Attachment 2 

§ 26.1303 Check for Completeness of Reports of Human Research Submitted for EPA Review 

AHE62 (MRID 48289614) 

Page 22 of 51 

Any person who submits to EPA data derived from human research covered by this subpart shall provide at the time of submission 

information concerning the ethical conduct of such research. To the extent available to the submitter and not previously provided to 

EPA, such information should include: 

Requirement Y/N Comments/Page References 

(a) Copies of all of the records relevant to the research specified by 

§26.1115(a) to be prepared and maintained by an IRB 

§1115(a)(1): Copies of 

• all research proposals reviewed, 

• scientific evaluations, if any, that accompany the proposals, 

• approved sample consent documents, 

• progress reports submitted by investigators, and reports of injuries to 

subjects. 

Y 

n/a 

Y 

Y 

Initially addressed in protocol 

Progress Rpt 244 

Close Out Report 318 

§1115(a)(2): Minutes of IRB meetings which shall be in sufficient detail to show 

• attendance at the meetings; 

• actions taken by the IRB; 

• the vote on these actions including the number of members voting 

for, against, and abstaining; 

• the basis for requiring changes in or disapproving research; 

• a written summary of the discussion of controverted issues and their 

resolution. 

Y p. 303 [Approval of Ongoing 

Research for AHE62] 

All other post-protocol approval 

reviews were done under 

expedited procedures and minutes 

were not created. 

§1115(a)(3): Records of continuing review activities. Y 301 

§1115(a)(4): Copies of all correspondence between the IRB and the investigators. Y 17-327 

§1115(a)(5): 

• A list of IRB members identified by name; earned degrees; representative 

capacity; indications of experience such as board certifications, licenses, 

etc., sufficient to describe each member’s chief anticipated contributions 

to IRB deliberations; 

• any employment or other relationship between each member and the 

institution 

N Already available to EPA 

§1115(a)(6): Written procedures for the IRB in the same detail as described in § 

26.1108(a) and § 26.1108(b). N Already available to EPA 

§1115(a)(7): Statements of significant new findings provided to subjects, as 

required by § 26.1116(b)(5). n/a 

(b) Copies of all of the records relevant to the 

information identified in §26.1125(a)-(f) 

§1125(a) 

A discussion of: 

(1) The potential risks to human subjects; Y Addressed in protocol 

(2) The measures proposed to minimize risks to the human subjects; Y Addressed in protocol 

(3): The nature and magnitude of all expected benefits of such research, 

and to whom they would accrue; Y Addressed in protocol 

(4) Alternative means of obtaining information comparable to what would 

be collected through the proposed research; and Y Addressed in protocol 

(5) The balance of risks and benefits of the proposed research. Y Addressed in protocol 

§1125(b): All information for subjects and written informed consent agreements as 

originally provided to the IRB, and as approved by the IRB. Y Orig. submitted 73-105,148-151 

Approved 154-213, 220-241 

§1125(c): Information about how subjects will be recruited, including any 

advertisements proposed to be used. Y Addressed in protocol 

Flyers (Spanish&English) 149-150 

§1125(d): A description of the circumstances and methods proposed for 

presenting information to potential human subjects for the purpose of obtaining 

their informed consent. 

Y Addressed in protocol 

§1125(e): All correspondence between the IRB and the investigators or sponsors. Y 17-327 

§1125(f): Official notification to the sponsor or investigator, in accordance with the 

requirements of this subpart, that research involving human subjects has been 

reviewed and approved by an IRB. 

Y 

Original approval provided in 

protocol submission; approved 

amendments 148, 152-3, 279 

(c) Copies of sample records used to document informed consent as specified by 

§26.1117, but not identifying any subjects of the research Y 220 English 230 Spanish 

(d) If any of the information listed in paragraphs (a) through (c) of this section is not 

provided, the person shall describe the efforts made to obtain the information. n/a 
Attachment 2 

§ 26.1303 Check for Completeness of Reports of Human Research Submitted for EPA Review 

AHE63 (MRID 48289615) 

Page 23 of 51 

Any person who submits to EPA data derived from human research covered by this subpart shall provide at the time of submission 

information concerning the ethical conduct of such research. To the extent available to the submitter and not previously provided to 

EPA, such information should include: 

Requirement Y/N Comments/Page References 

(a) Copies of all of the records relevant to the research specified by 

§26.1115(a) to be prepared and maintained by an IRB 

§1115(a)(1): Copies of 

• all research proposals reviewed, 

• scientific evaluations, if any, that accompany the proposals, 

• approved sample consent documents, 

• progress reports submitted by investigators, and reports of injuries to 

subjects. 

Y 

n/a 

Y 

Y 

Initially addressed in protocol 

Progress Rpt 105 

Close Out Report 198 

§1115(a)(2): Minutes of IRB meetings which shall be in sufficient detail to show 

• attendance at the meetings; 

• actions taken by the IRB; 

• the vote on these actions including the number of members voting 

for, against, and abstaining; 

• the basis for requiring changes in or disapproving research; 

• a written summary of the discussion of controverted issues and their 

resolution. 

Y p. 163 [Approval of Ongoing 

Research for AHE63] 

All other post-protocol approval 

reviews were done under 

expedited procedures and minutes 

were not created. 

§1115(a)(3): Records of continuing review activities. Y 100 

§1115(a)(4): Copies of all correspondence between the IRB and the investigators. Y 13-219 

§1115(a)(5): 

• A list of IRB members identified by name; earned degrees; representative 

capacity; indications of experience such as board certifications, licenses, 

etc., sufficient to describe each member’s chief anticipated contributions 

to IRB deliberations; 

• any employment or other relationship between each member and the 

institution 

N Already available to EPA 

§1115(a)(6): Written procedures for the IRB in the same detail as described in § 

26.1108(a) and § 26.1108(b). N Already available to EPA 

§1115(a)(7): Statements of significant new findings provided to subjects, as 

required by § 26.1116(b)(5). n/a 

(b) Copies of all of the records relevant to the 

information identified in §26.1125(a)-(f) 

§1125(a) 

A discussion of: 

(1) The potential risks to human subjects; Y Addressed in protocol 

(2) The measures proposed to minimize risks to the human subjects; Y Addressed in protocol 

(3): The nature and magnitude of all expected benefits of such research, 

and to whom they would accrue; Y Addressed in protocol 

(4) Alternative means of obtaining information comparable to what would 

be collected through the proposed research; and Y Addressed in protocol 

(5) The balance of risks and benefits of the proposed research. Y Addressed in protocol 

§1125(b): All information for subjects and written informed consent agreements as 

originally provided to the IRB, and as approved by the IRB. Y 

Orig. submitted – In protocol 

submission; also 54-64 

Approved 67-97 

§1125(c): Information about how subjects will be recruited, including any 

advertisements proposed to be used. Y Addressed in protocol; 96-97 Flyers (Spanish&English) 67, 81 

§1125(d): A description of the circumstances and methods proposed for 

presenting information to potential human subjects for the purpose of obtaining 

their informed consent. 

Y Addressed in protocol 

§1125(e): All correspondence between the IRB and the investigators or sponsors. Y 13-219 

§1125(f): Official notification to the sponsor or investigator, in accordance with the 

requirements of this subpart, that research involving human subjects has been 

reviewed and approved by an IRB. 

Y 

Original approval provided in 

protocol submission; approved 

amendments 66, 95, 159,174,194 

(c) Copies of sample records used to document informed consent as specified by 

§26.1117, but not identifying any subjects of the research Y 

202 (English); None of the 

subjects in this study chose to use 

the Spanish version of the forms 

(d) If any of the information listed in paragraphs (a) through (c) of this section is not 

provided, the person shall describe the efforts made to obtain the information. n/a 
Attachment 2 

§ 26.1303 Check for Completeness of Reports of Human Research Submitted for EPA Review 

AHE64 (MRID 48289616) 

Page 24 of 51 

Any person who submits to EPA data derived from human research covered by this subpart shall provide at the time of submission 

information concerning the ethical conduct of such research. To the extent available to the submitter and not previously provided to 

EPA, such information should include: 

Requirement Y/N Comments/Page References 

(a) Copies of all of the records relevant to the research specified by 

§26.1115(a) to be prepared and maintained by an IRB 

§1115(a)(1): Copies of 

• all research proposals reviewed, 

• scientific evaluations, if any, that accompany the proposals, 

• approved sample consent documents, 

• progress reports submitted by investigators, and reports of injuries to 

subjects. 

Y 

n/a 

Y 

Y 

Initially addressed in protocol 

Progress Rpt 156 

Close Out Report 200 

§1115(a)(2): Minutes of IRB meetings which shall be in sufficient detail to show 

• attendance at the meetings; 

• actions taken by the IRB; 

• the vote on these actions including the number of members voting 

for, against, and abstaining; 

• the basis for requiring changes in or disapproving research; 

• a written summary of the discussion of controverted issues and their 

resolution. 

Y 

p. 182 [Protocol Amendment 2] 

p. 195 [Approval of Ongoing 

Research for AHE64] 

All other post-protocol approval 

reviews were done under 

expedited procedures and minutes 

were not created. 

§1115(a)(3): Records of continuing review activities. Y 156 

§1115(a)(4): Copies of all correspondence between the IRB and the investigators. Y 14-217 

§1115(a)(5): 

• A list of IRB members identified by name; earned degrees; representative 

capacity; indications of experience such as board certifications, licenses, 

etc., sufficient to describe each member’s chief anticipated contributions 

to IRB deliberations; 

• any employment or other relationship between each member and the 

institution 

N Already available to EPA 

§1115(a)(6): Written procedures for the IRB in the same detail as described in § 

26.1108(a) and § 26.1108(b). N Already available to EPA 

§1115(a)(7): Statements of significant new findings provided to subjects, as 

required by § 26.1116(b)(5). n/a 

(b) Copies of all of the records relevant to the 

information identified in §26.1125(a)-(f) 

§1125(a) 

A discussion of: 

(1) The potential risks to human subjects; Y Addressed in protocol 

(2) The measures proposed to minimize risks to the human subjects; Y Addressed in protocol 

(3): The nature and magnitude of all expected benefits of such research, 

and to whom they would accrue; Y Addressed in protocol 

(4) Alternative means of obtaining information comparable to what would 

be collected through the proposed research; and Y Addressed in protocol 

(5) The balance of risks and benefits of the proposed research. Y Addressed in protocol 

§1125(b): All information for subjects and written informed consent agreements as 

originally provided to the IRB, and as approved by the IRB. Y 

Orig. submitted – In protocol 

submission; also 54-64 

Approved 66-86 

§1125(c): Information about how subjects will be recruited, including any 

advertisements proposed to be used. Y Addressed in protocol; 153-4 Flyers (Spanish&English) 88, 89 

§1125(d): A description of the circumstances and methods proposed for 

presenting information to potential human subjects for the purpose of obtaining 

their informed consent. 

Y Addressed in protocol 

§1125(e): All correspondence between the IRB and the investigators or sponsors. Y 14-217 

§1125(f): Official notification to the sponsor or investigator, in accordance with the 

requirements of this subpart, that research involving human subjects has been 

reviewed and approved by an IRB. 

Y 

Original approval provided in 

protocol submission; approved 

amendments 152, 182 

(c) Copies of sample records used to document informed consent as specified by 

§26.1117, but not identifying any subjects of the research Y 

203 (English); None of the 

subjects in this study chose to use 

the Spanish version of the forms 

(d) If any of the information listed in paragraphs (a) through (c) of this section is not 

provided, the person shall describe the efforts made to obtain the information. n/a 
Attachment 3 

Responsiveness to Major EPA and HSRB Comments 

Page 25 of 51 

Table D. Responsiveness to Major EPA and HSRB Comments on Protocols for AHE62, AHE63, AHE64 

(reviewed at the October 2008 HSRB Meeting)

EPA or HSRB Comment Addressed before executing 

AHE62, AHE63, AHE64? 

1. Characterize representativeness of subjects Yes 

1. 5 monitoring units in each cluster, each from a different 

farm, is needed to ensure that the design and analyses are 

scientifically sound. 

Only 1 worker monitored per employer 

2. Select of Local Site Coordinators with demonstrable 

training and expertise in survey implementation to ensure 

optimal recruiting and thereby enhance the usefulness of the 

data 

Yes 

3. The Local Site Coordinator, the Principal Field Investigator, 

the Field Facility, the Analytical Facility, and the Principal 

Analytical Investigator must be identified in the protocol 

Yes, addressed prior to study initiation 

4. Any key members of the research team who will have 

contact with the research subjects or their identifiable data 

must receive and document their recent (not expired) 

training in human subjects’ protection 

Yes, and relevant SOP subsequently revised 

(SOP AHETF-10.C.4) 

5. Revise subject recruitment plan to specifically address the 

probability that subjects may also be growers. 

Yes (SOP AHETF-11.B.4) 

6. Remove risks of agricultural work from the listing of risks 

related to the research. 

Yes 

7. Identify risks of pesticide products that are due to scripting. Yes 

8. Harmonize the lists of eligibility factors in the protocol and 

the consent form 

Yes 

9. The number of potentially eligible workers linked to each 

grower, the numbers attending initial group meetings, 

attending individual consent interviews, signing consent 

forms, subsequently withdrawing or being withdrawn, and 

completing participation should all be recorded and reported 

Yes 
ATTACHMENT 4:

Heat Index Records from Raw Data for

AHE62, AHE63, AHE64

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Heat Index Records

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