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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

 WASHINGTON D.C., 20460 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION

January 7, 2010 

MEMORANDUM 

SUBJECT: Ethics Review of Completed AHETF Closed 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: Smith, Larry D. (2010) Determination of Dermal and Inhalation Exposure 

to Workers During Airblast Applications of Liquid Sprays Using Closed 

Cab Equipment in Florida Citrus. Study Number AHE55. 377 p. (MRID 

48289601) [Volume 1]

 Smith, Larry D. (2010) IIRB Correspondence Report for Cluster Report 

AHE55. 287 p. (MRID 48303503) [Volume 2]

 Smith, Larry D. (2010) Determination of Dermal and Inhalation Exposure 

to Workers During Airblast Applications of Liquid Sprays Using Closed 

Cab Equipment in Georgia Pecans. Study Number AHE56. 379 p. 

(MRID 48289602) [Volume 3]

 Smith, Larry D. (2010) IIRB Correspondence Report for Cluster Report 

AHE56. 295 p. (MRID 48303504) [Volume 4]

 Smith, Larry D. (2010) Determination of Dermal and Inhalation Exposure 

to Workers During Airblast Applications of Liquid Sprays Using Closed 

Cab Equipment in Michigan Stone Fruit. Study Number AHE57. 377 p. 

(MRID 48303501) [Volume 5]
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 Smith, Larry D. (2010) IIRB Correspondence Report for Cluster Report 

AHE57. 172 p. (MRID 48289608) [Volume 6]

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

to Workers During Airblast Applications of Liquid Sprays Using Closed 

Cab Equipment in California Trellis Crops. Study Number AHE58. 282 

p. (MRID 48289604) [Volume 7]

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

AHE58. 357 p. (MRID 48289609) [Volume 8]

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

to Workers During Airblast Applications of Liquid Sprays Using Closed 

Cab Equipment in Washington Pome Fruit. Study Number AHE59. 220 

p. (MRID 48303502) [Volume 9]

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

AHE59. 195 p. (MRID 48289610) [Volume 10]

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 five 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 vehicle with an enclosed 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 

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

sprayed tree or trellis crops in five different states in the U.S where closed cab airblast 

equipment is commonly 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 

AHE55 FL Orange, Tangerine 5 All male 20-70 

AHE56 GA Pecan 5 All male 43-68 

AHE57 MI Cherry 5 4 males, 1 female 21-58 

AHE58 CA Grape 5 All male 27-49 

AHE59 WA Apple 4 All male 26-62 

The background and ethics-related chronology for each field study is summarized below. 
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1.1 AHE55

The scenario design and protocol for AHE55 were approved by the overseeing 

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

in March 2008 and submitted to EPA for review in April 2008. The protocol and EPA’s 

review dated May 27, 2008 were discussed by the Human Studies Review Board (HSRB) 

at its June 2008 meeting. The HSRB review was generally favorable, and the Board’s 

November 14, 2008 final report of the June 2008 meeting concluded, with respect to 

ethics, that “with a number of required revisions, [the protocols] appear likely to generate 

scientifically sound, useful information and to meet the applicable provisions of the EPA 

regulations in 40 CFR part 26, subparts K and L.” 

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

for AHE55 were revised to address EPA and HSRB comments. The revised protocol was 

submitted to IIRB on July 18, 2008, and approved on July 21, 2008. There are no other 

amendments to the protocol documented in the IIRB correspondence volume for AHE55 

(Vol 2). 

Subject monitoring for AHE55 took place in late October 2008. Five male 

subjects between the ages of 20 and 70 were monitored for dermal and inhalation 

exposure while applying pesticide sprays using closed-cab airblast equipment to orange 

and tangerine crops in Florida. There was one reported deviation during the field phase 

of the research, and there were no reported deviations during the analytical phase. I 

noted 4 unreported deviations. 

A detailed chronology of the ethics-related study activities for AHE55 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 18. 

1.2 AHE56

The scenario design and protocol for AHE56 was approved by IIRB in March 

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

dated May 27, 2008 were discussed by the Human Studies Review Board (HSRB) at its 

June 2008 meeting. The HSRB review was generally favorable, and the Board’s 

November 14, 2008 final report of the June 2008 meeting concluded, with respect to 

ethics, that “with a number of required revisions, [this protocol appears] likely to 

generate scientifically sound, useful information and to meet the applicable provisions of 

the EPA regulations in 40 CFR part 26, subparts K and L.” 

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

for AHE56 were revised to address EPA and HSRB comments. The revised protocol was 

submitted to IIRB on July 18, 2008, and approved on July 21, 2008. There are no other 

amendments to the protocol documented in the IIRB correspondence volume for AHE56 

(Vol 4). 

 ` 
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Subject monitoring for AHE56 took place in August 2008. Five male subjects 

between the ages of 43 and 68 were monitored while applying pesticide sprays using 

closed-cab airblast equipment to pecans in Georgia. There were five reported deviations 

during the field phase of the research, and three reported deviations during the analytical 

phase. I noted one unreported deviation. EPA presented preliminary recruiting results 

from AHE56 at the October 2008 HSRB meeting. 

A detailed chronology of the ethics-related study activities for AHE56 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 18. 

1.3 AHE57

The scenario design and protocol for AHE57 was approved by IIRB 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; the Board’s December 30, 2008 final report of the 

October 2008 meeting concluded, with respect to ethics, that “if revised as suggested by 

the Board, 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 forms, and recruiting materials 

for AHE57 were revised to address EPA and HSRB comments. The revised protocols, 

consent forms, and recruiting materials for AHE57 were submitted to IIRB on January 

16, 2009, and approved on January 19, 2009. There are no other amendments to the 

protocol documented in the IIRB correspondence volume for AHE57 (Vol 6). 

Subject monitoring for AHE57 took place in May 2009. Four male subjects and 

one female subject between the ages of 21 and 58 were monitored while applying 

pesticide sprays using closed-cab airblast equipment to cherries in Michigan. There was 

one reported deviation during the field phase of the research and four reported deviations 

during the analytical phase. I noted two unreported deviations. 

After monitoring, an amendment to the purity analysis section of the protocol 

(Section 7.5.3) was submitted to IIRB. This Amendment was not acknowledged by IIRB 

until after the study was closed, but IIRB concluded that the amendment was 

“administrative in nature, did not affect subject safety, and would not have received a 

revision to the consent form.” 

A detailed chronology of the ethics-related study activities for AHE57 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 18. 

 
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1.4 AHE58

The scenario design and protocol for AHE58 was approved by IIRB 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; the Board’s December 30, 2008 final report of the 

October 2008 meeting concluded, with respect to ethics, that “if revised as suggested by 

the Board, 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 forms, and recruiting materials 

for AHE58 were revised to address comments from EPA, HSRB, and the California 

Department of Pesticide Regulation. The revised protocol, consent form, and recruiting 

materials for AHE58 were submitted to IIRB on March 26, 2009, and approved on April 

1 and April 6, 2009. Two subsequent amendments were approved by IIRB in June and 

July 2009. 

Subject monitoring for AHE58 took place in June and July 2009. Five male 

subjects between the ages of 27 and 49 were monitored while applying pesticide sprays 

using closed-cab airblast equipment to grapes in California. There were four reported 

deviations in the field phase of the study, and one reported deviation in the analytical 

phase. I noted three unreported deviations. 

A detailed chronology of the ethics-related study activities for AHE58 is provided 

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

deviations from all studies is provided in Table 2, on page 18. 

1.5 AHE59

The scenario design and protocol for AHE59 was approved by IIRB and 

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

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

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

October 2008 meeting concluded, with respect to ethics, that “if revised as suggested by 

the Board, 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 forms, and recruiting materials 

for AHE59 were revised to address EPA and HSRB. The revised protocol, consent form, 

and recruiting materials for AHE59 were submitted to IIRB on January 16, 2009, and 

approved on January 19, 2009. There was one additional amendment in May 2009 to add 

two additional carbaryl products to the list of approved test substances. 

Subject monitoring for AHE59 took place in late April and early May 2009. Four 

male subjects between the ages of 26 and 62 were monitored while applying pesticide 
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sprays to apple crops in Washington using closed-cab airblast equipment. A fifth subject 

was not monitored because of a series of logistical difficulties.1 

There were two reported field phase deviations, and one reported analytical phase 

deviation. I noted three unreported deviations. 

A detailed chronology of the ethics-related study activities for AHE59 is provided 

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

deviations from all studies is provided in Table 2, on page 18. 

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 10 study volumes identified on pages 1-2, plus Supplement 1 related 

to AHE57. 

3.0 Protocol Amendments: 

3.1 AHE55

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 July 18, 2008, and approved on July 21, 2008. No further 

amendments are documented in the IIRB Correspondence Report (Volume 2). The study 

report (Volume 1) indicates that the protocol was amended three times prior to execution 

of the field phase, but the report does not summarize these changes. The discrepancy in 

the reporting of amendments between Volume 1 and Volume 2 is not resolved or 

explained elsewhere in the AHETF’s submission. 

3.2 AHE56

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 July 18, 2008, and approved on July 21, 2008. No further 

amendments are documented in the IIRB Correspondence Report (Volume 2). The study 

 

1 One subject was enrolled and signed the consent form, but he was not ultimately monitored because a 

research team was not available on the day that he needed to make his application. Researchers attempted 

to enroll and monitor an alternate grower, but that grower’s air conditioned closed cab tractor was not 

functioning on the day that the application needed to take place, so the grower applied the pesticide with an 

open cab tractor and the research did not take place. The timing of carbaryl apple-thinning application is 

dependent on crop growth state and weather, and as a result, the applications could not be pre-scheduled; 

researchers needed to be available when the grower intended to make an application. Several attempts 

were made to find a fifth subject by re-contacting the other Potentially Eligible Growers, but none was 

found before the use season ended. 
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report (Volume 1) indicates that the protocol was amended two times prior to execution 

of the field phase, but the report does not summarize these changes. The discrepancy in 

the reporting of amendments between Volume 3 and Volume 4 is not resolved or 

explained elsewhere in the AHETF’s submission. 

3.3 AHE57

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. 

In June 2009, the AHETF submitted to IIRB an amendment to the purity analysis 

section of the protocol (Section 7.5.3). The IIRB Correspondence Report (Volume 6) 

shows that the amendment was emailed to IIRB on June 7, 2009. In September 2010, 

after the study was closed, AHETF realized that it did not have documentation of IIRB’s 

approval of the amendment, and requested copies of IIRB’s records on the amendment. 

AHETF was informed at that time that IIRB did not have a record of the amendment. On 

September 14, 2010, IIRB acknowledged receipt of the amendment, and noted that the 

amendment was “administrative in nature, did not affect subject safety, and would not 

have received a revision to the consent form.” In EPA’s view, this amendment did not 

affect subject safety or subject autonomy, and therefore the documentation issues are not 

important in evaluating the ethical conduct of this research. 

There is agreement between the study report (Volume 5) and IIRB 

Correspondence Report (Volume 6) that there were two amendments to AHE57 prior to 

execution of the field phase of the research. 

3.4 AHE58 

Following EPA’s and HSRB’s reviews, the protocol, consent forms, and 

recruiting materials were revised to address EPA, HSRB, and California Department of 

Pesticide Regulation comments. The revised protocol, consent form, and recruiting 

materials for AHE58 were submitted to IIRB on March 26, 2009, and approved on April 

1 and April 6, 2009. 

In early June 2009, the AHETF consulted EPA about three changes to the AHE58 

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 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 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. IIRB approved the amendment on July 22, 2009. 

There is agreement between the study report (Volume 7) and IIRB 

Correspondence Report (Volume 8) for AHE58 that there were three amendments to 

AHE58. 

3.5 AHE59

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. 

In April 2009, while preparing to conduct the monitoring for AHE59, the AHETF 

learned that two eligible growers wanted to use carbaryl products that were not on the list 

of approved surrogate products. In order to expand the list of surrogates to include these 

two products, AHETF submitted to IIRB new product risk statements (PRSs) for the two 

carbaryl end-use products on April 24, 2009; IIRB approved the new PRSs on April 29, 

2009. On May 11, 2009, the AHETF submitted to IIRB an amendment, which had 

previously been approved by EPA, to add two carbaryl end-use products to the list of 

possible products for this study. IIRB approved this amendment on May 19, 2009. This 

amendment was not timely, however, because two subjects were monitored using the two 

new carbaryl products on May 7 and 9, 2009. This situation was later reported to IIRB as 

a deviation. Please refer to the discussion on page 16 of this review for more 

information. 
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There is agreement between the study report (Volume 9) and IIRB 

Correspondence Report (Volume 10) that there was one amendment to AHE59 after the 

protocol was signed by the study director. 

4.0 Protocol Deviations: 

4.1 AHE55

 

 4.1.1 Reported Deviations

There was one reported deviation during the field phase of AHE55. On two 

occasions, a subject was selected for monitoring from two potential subjects by coin flip 

rather than by drawing a name as required by the protocol. This deviation occurred on 

October 28 and October 30, 2008, and was reported to IIRB on November 16, 2008. On 

November 17th, 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 because it did not place subjects at increased risk and was consistent with the 

general intent of the protocol that subjects be selected randomly if more than one eligible 

individual is available for monitoring. I defer to the EPA science reviewer about whether 

this deviation is important from a science perspective. 

There were no reported deviations in the analytical phase of the research. 

4.1.2 Unreported Deviations

There were four unreported deviations during the field phase of AHE55. 

1) Section 2.4 of the protocol states that growers will be reimbursed for the 

pesticide used in the study, but for AHE55, the Local Site Coordinator 

purchased the product and delivered it to the application sites. 

Notwithstanding the study director’s failure to report this deviation to IIRB, it 

raises no ethical issues. I defer to the EPA science reviewer on whether the 

deviation raises science issues. 

2) One subject was a non-reader who required a witness for the consent process. 

Section 2.7 of the protocol states that “Witnesses must have no association 

with AHETF, its member companies, researchers, growers, or workers.” (Vol 

1, p 348). In this study, the non-reading worker selected the witness (“The 

witness was selected by the participant and monitored the informed consent 

procedure.” [Vol. 1, p. 10]) This is an unreported protocol deviation because 

the witness had an association with the worker. This deviation does not raise 

concerns about the consent process for this worker, however, because even 

though the protocol for AHE55 states that the witness should not have an 

association with the worker, the protocols for AHE57, AHE58, and AHE59 
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specify that the witness should be selected by the non-reading prospective 

subject. Moreover, SOP 11.I.1 states that subjects may choose a witness, and 

only specifies that “the witness must be unassociated with the conduct of the 

research (i.e., not employed by the Sponsor or any of its contractors.)” 

The HSRB, in its December 18, 2007, report of the June 2007 HSRB meeting, 

stated the following on the topic of witnesses: 

“The Board expressed support for the Agency's proposal to have 

impartial third-party witnesses observe the consent process when a 

research subject is unable to read relevant study documents. As 

specific studies are proposed, however, it will be important for 

investigators to describe the procedures to be employed in recruiting 

these witnesses. It would be inappropriate, for example, to ask 

translators to serve as witnesses (as suggested in the materials 

reviewed by the Board), because one of the main purposes of 

employing a witness is to ensure that the communication of studyrelated materials is adequate (and the translator would be conflicted 

with regard to that assessment). If feasible, the Agency may wish to 

consider using impartial “consent monitors” or “research subject 

advocates” as witnesses, as is increasingly done in certain clinical 

studies.” (p. 64-5 of 67) 

Although this protocol deviation should have been reported to IIRB, it raises 

no ethics issues. It is appropriate, in EPA’s view, for the non-reading subject 

to select the witness. The important restriction that the witness not be 

associated with the researchers or study sponsors was not violated in this case. 

3) One subject touched the cab door while not wearing gloves, and later opened 

the cab door with bare hands. There is no record that the observer reminded 

the worker to wear his gloves or reported the behavior to the study director, 

which violated protocol section 2.3.2 and SOP AHETF-10.C.4. These 

protocol and SOP violations were not reported to IIRB. These deviations are 

discussed in greater detail in sections 8.1 and 10.0 of this review. 

4) Four of the five subjects in this study did not spray for a minimum of 4 hours, 

as required in Section 7.8 of the protocol (“Each MU shall consist of a period 

of at least 4 hours of spraying and at least 3 tank loads of the spray mixture.”) 

See Table F in Appendix 2 for individual spray times for each subject. 

Although this protocol deviation should have been reported to IIRB, it raises 

no ethics issues. I defer to the EPA science reviewer on whether this 

deviation raises science issues. 
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4.2 AHE56

 

 4.2.1 Reported Deviations

There were five reported deviations during the field phase of AHE56. 

1) In the summer of 2008, the AHETF identified potential eligible pecan growers 

in southwest Georgia (located in the five counties adjacent to Tift County), in 

accordance with Section 4.0 of the AHE56 protocol (Vol 3, p 347 of 379). By 

mid-August, the AHETF had identified 22 eligible growers who agreed to 

participate in the study by providing the closed-cab equipment and allowing 

their pecan trees to be sprayed with one of the surrogate products. In the final 

phase of recruitment, the study director made telephone contact with and/or 

visited the 22 eligible growers to select at least five growers who could 

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

efficiently. During the course of conducting the telephone conversations with 

eligible growers, the study director was informed of two additional pecan 

growers who might be candidates for participation in the study. One of these 

referrals appeared on the original grower list, but was eliminated because he 

was no longer growing pecans and was now working as a commercial 

applicator; the other referral did not appear on the original grower list because 

his farm was not located in one of the five counties adjacent to Tift County. 

During the week of August 18, 2008, the AHETF had six growers ready to 

participate (five were needed; one was to serve as a back-up). The research 

team assembled in Tifton, Georgia on August 19, and they planned to begin 

monitoring on August 21st. However, a tropical storm struck on August 20th, 

making the field work impossible for several days. When the research was 

ready to proceed during the week of August 25th, three of the six growers were 

either no longer willing to participate or unable to be rescheduled within the 

necessary timeframe to efficiently conduct the research. In order to find the 

additional two needed growers, the AHETF contacted the two “referrals,” and 

these two growers eventually agreed to participate. This was a deviation since 

the protocol does not provide for recruitment beyond the eligible growers list, 

and because one of the subjects was not located in a county directly adjacent 

to Tift County. 

The decision to use the two referred growers in the study was made during the 

week of August 25th. The deviation was reported to IIRB on September 5, 

2008. On September 15, IIRB acknowledged the deviation and concluded 

that it did not place subjects at increased risk. I note that the deviation was 

reported to have occurred on August 18th, but the field notes show that the 

monitoring took place on August 25-28. In EPA’s view, this deviation is not 

significant from an ethics perspective because after the initial identification of 

the two referred growers, they were recruited using the procedures that are 
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outlined in the protocol and SOP AHETF-11.B.3. I defer to the EPA science 

reviewer on whether this deviation affects the scientific integrity of the data. 

2) The second reported deviation involved a departure from Section 2.7 of the 

protocol, which says that informed consent must be obtained before a subject 

participates in the research. In this instance, one of the subjects dressed in the 

dosimeter before he signed the consent form. He is reported to have given 

oral consent prior to donning the dosimeter, but he signed the consent form 

shortly after putting on the dosimeter. The reason for the deviation was that 

the subject (A5) arrived at the field site just before another subject (A1) was 

expected to return to the staging area to remove his dosimeter and have his 

samples collected. To avoid the possibility of contamination of subject A5’s 

clean dosimeter while subject A1 was having his samples collected, subject 

A5 was quickly dressed in his dosimeter before subject A1 entered the staging 

area. 

Based on the field observation records, the deviation occurred on August 25, 

2008, the first day of monitoring. However, the deviation was mistakenly 

reported to IIRB as having occurred on August 18th. The deviation was 

reported to IIRB on September 17, and IIRB acknowledged it on September 

23rd and concluded subjects were not at increased risk. In EPA’s view, this 

deviation is not significant from an ethics perspective because the subject 

gave verbal consent before putting on the dosimeter, and he signed the 

consent form shortly after putting on the dosimeter. It is questionable whether 

this is indeed a deviation since the subject gave oral consent prior to putting 

on the dosimeter, but the AHETF wisely erred on the side of caution by 

reporting this deviation. 

3) The third reported deviation for AHE56 was that travel fortification samples, 

which should have been prepared on day 1, were not prepared until 

monitoring day 4. The deviation was reported to IIRB on September 17, and 

IIRB acknowledged it on September 23rd and concluded subjects were not at 

increased risk. I note that the deviation report erroneously indicates that the 

deviation occurred on August 18-21. Based on the field notes providing the 

dates that subjects were monitored, this deviation occurred on August 25-28, 

2008. This deviation has no effect on the ethical conduct of the research. I 

defer to the EPA science reviewer on whether this deviation affects the 

scientific integrity of the study. 

4) The fourth reported deviation for AHE56 was that one subject (subject A4) 

took a bathroom break without first washing his hands and without handwash 

samples being taken. The subject stepped away from the tractor to relieve 

himself behind a tree while his spray tank was being refilled. The worker was 

out of sight of the observer at that time. When the observer realized what had 

happened, he reminded the worker to follow label directions advising that 

users should wash hands before using the bathroom. This was a violation of 
Page 13 of 43 

label directions, and also a deviation from SOP AHETF-8.B.4 (section 5.2). 

From an ethics perspective, the observer responded appropriately to the 

situation by reminding the worker of label directions, but he should have also 

reported the occurrence to the study director in accordance with SOP AHETF10.C.3. The deviation was reported to IIRB on September 17, and IIRB 

acknowledged it on September 23rd and concluded that subjects were not at 

increased risk. I note that the deviation report erroneously indicates that the 

deviation occurred between August 18-21, 2008. Based on the field notes 

providing the dates that subjects were monitored, this deviation occurred on 

August 28, 2008. This deviation raises no ethical issues, but I defer to the 

EPA science reviewer on whether this deviation affects the scientific integrity 

of the data. 

5) The fifth reported deviation for AHE56 was that the air pump and sampling 

train were removed from subjects before the final air flow rate was measured 

with a calibrated rotometer. This was a deviation from SOP AHETF-8.D.2 

(Section 4.11). The deviation was reported to IIRB on September 17, and 

IIRB acknowledged it on September 23rd and concluded that subjects were 

not at increased risk. I note that the deviation report erroneously indicates that 

the deviation occurred between August 18-21, 2008. Based on the field notes 

providing the dates that subjects were monitored, this deviation occurred on 

August 28, 2008. This deviation raises no ethical issues, but I defer to the 

EPA science reviewer on whether this deviation affects the scientific integrity 

of the data. 

There were four deviations in the analytical phase of the research that were reported to 

IIRB. These deviations raise no ethical issues, but I defer to the EPA science reviewer on 

whether these deviations affect the scientific integrity of the data. 

4.2.2 Unreported Deviations

 

1) None of the five subjects in this study sprayed for a minimum of 4 hours, as 

required in Section 7.8 of the protocol (“Each MU shall consist of a period of 

at least 4 hours of spraying and at least 3 tank loads of the spray mixture.”) 

See Table F in Appendix 2 for individual spray times for each subject. 

Although this protocol deviation should have been reported to IIRB, it raises 

no ethics issues. I defer to the EPA science reviewer on whether this 

deviation raises science issues. 

4.3 AHE57

 

 4.3.1 Reported Deviations

There was one reported deviation during the field phase of AHE56. Subject A1, 

who was assigned to the lowest stratum of amount active ingredient handled (AaiH) – 
Page 14 of 43 

5 to 9 pounds – actually handled 10.68 pounds. In addition, this subject was monitored 

for only 2 hours and he applied only 2 tank loads, contrary to the protocol requirement in 

Section 7.8 that subjects are monitored for a minimum of 4 hours and apply at least 3 

tank loads. The reason given for applying an amount outside of the limits of the stratum 

was that the grower needed the pesticide applied at a higher rate to achieve effective 

control of the target pest. The minimum application time and minimum number of loads 

specified in the protocol could not be achieved because of the grower’s preference to use 

his normal tractor speed and spray volume. The deviation occurred on May 22, 2009, 

and was reported to IIRB on June 4, 2009. On June 10, 2009, IIRB acknowledged the 

deviation and indicated that no additional action is 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 were 4 deviations in the analytical phase of the research that were reported 

to IIRB. These deviations raise no ethical issues, but I defer to the EPA science reviewer 

on whether these deviations affect the scientific integrity of the data. 

4.3.2 Unreported Deviations

1) None of the five subjects in this study sprayed for a minimum of 4 hours, as 

required in Section 7.8 of the protocol (“Each MU shall consist of a period of 

at least 4 hours of spraying and at least 3 tank loads of the spray mixture.”) 

See Table F in Appendix 2 for individual spray times for each subject. 

Although this protocol deviation should have been reported to IIRB, it raises 

no ethics issues. I defer to the EPA science reviewer on whether this 

deviation raises science issues. 

4.4 AHE58

 

 4.4.1 Reported Deviations

There were four reported deviations during the field phase of AHE58. 

1) The first deviation was that on Study Day 2, inner whole body dosimeters 

were inadvertently not folded over after field fortifications were conducted 

and prior to covering with cloth as specified in SOP AHETF-8.E.5. The 

deviation occurred on July 1, 2009, and was reported to IIRB on September 2, 

2009. On September 3rd, IIRB acknowledged the deviation and concluded no 

further action was required. This deviation raises no ethical issues. I defer to 

the EPA science reviewer on whether it raises science issues. 

2) The second deviation was that low level field fortifications for the hand wash 

and face/neck wipes were conducted in duplicate on day 4 instead of in 

triplicate. The deviation occurred on August 7, 2009, and was reported to 

IIRB on September 2, 2009. On September 3rd, IIRB acknowledged the 
Page 15 of 43 

deviation and concluded no further action was required. This deviation raises 

no ethical issues. I defer to the EPA science reviewer on whether it raises 

science issues. 

3) The third deviation was that subject A5 was monitored for 3 hours 8 minutes, 

contrary to the requirement in Section 7.8 of the protocol that subjects apply 

for a minimum of 4 hours. The deviation occurred on August 10, 2009, and 

was reported to IIRB on September 2, 2009. On September 3rd, IIRB 

acknowledged the deviation and concluded no further action was required. 

This deviation raises no ethical issues. I defer to the EPA science reviewer on 

whether it raises science issues. 

4) The fourth deviation was that the field fortifications were done at levels 

different than those specified in protocol. The deviation was discovered upon 

inspection of the laboratory records, which showed that the laboratory 

technician preparing the fortification vials and tubes made several dilution 

errors that resulted in the field researchers using incorrect fortification levels. 

The deviation occurred on June 10 and 11, 2009, and it was reported to IIRB 

on December 7, 2009. On December 15th, IIRB acknowledged the deviation 

and concluded no further action was required. This deviation raises no ethical 

issues. I defer to the EPA science reviewer on whether it raises science issues. 

There was one deviation in the analytical phase of the research that was reported 

to IIRB. This deviation raises no ethical issues, but I defer to the EPA science reviewer 

on whether the deviation affects the scientific integrity of the data. 

4.4.2 Unreported Deviations

There were four unreported deviations during the field phase of AHE58. 

1. One subject touched the equipment while not wearing gloves. There is no 

record that the observer reminded the worker to wear his gloves or that the 

observer reported the behavior to the study director, which violated protocol 

section 2.3.2, SOP AHETF-10.C.4, and SOP AHETF-11.E.1. These protocol 

and SOP violations were not reported to IIRB. These deviations are discussed 

in greater detail in sections 8.1 and 10.0 of this review. 

2. Protocol section 7.8 states that “a single MU will be conducted in this study 

from each of the five strata” (Vol 7, p. 253). In the conduct of the study, 

however, two subjects applied amounts from the highest stratum (56-100 lbs) 

and no worker applied from the second stratum (10-17 lbs) (Vol 7, p 43). 

This deviation was not reported to IIRB. Notwithstanding the investigator’s 

failure to report the deviation to IIRB, I conclude that the deviation does not 

raise ethics issues. I defer to the EPA science reviewer on whether the 

deviation raises science issues. 
Page 16 of 43 

3. At least one of the five subjects in this study failed to spray for a minimum of 

4 hours, as required in Section 7.8 of the protocol (“Each MU shall consist of 

a period of at least 4 hours of spraying and at least 3 tank loads of the spray 

mixture.”) It is not possible to calculate spray times from the observer logs 

for this study. However, the dermal monitoring time for one of the workers 

was less than four hours, which means that spray time was indeed below 4 

hours for this subject. It is possible that other subjects in AHE58 also sprayed 

for less than 4 hours. See Table F in Appendix 2 for individual spray times 

for each subject. Although this protocol deviation should have been reported 

to IIRB, it raises no ethics issues. I defer to the EPA science reviewer on 

whether this deviation raises science issues. 

4.5 AHE59

 

 4.5.1 Reported Deviations

There were two reported deviations during the field phase of AHE59. 

1) Two subjects were monitored on May 7 and May 9, 2009 while applying 

carbaryl products that were not on the list of approved surrogate products in 

Section 7.5 of the protocol. The reason for the deviation was that two of the 

growers would agree to participate only if they could use carbaryl products 

which were not on the list of approved surrogates in the protocol. When the 

AHETF learned of the two growers’ preferences for these two particular 

carbaryl products, the Task Force contacted EPA and provided copies of 

Product Risk Statements (PRSs) for the two carbaryl products. EPA reviewed 

the products and approved their addition to the list of possible test substances. 

The AHETF next submitted the new PRSs to IIRB on April 24, 2009, and 

IIRB approved the new PRSs on April 29, 2009. However, the AHETF erred 

in not simultaneously submitting an amendment to add the products to the 

protocol. The AHETF recognized the error, and submitted an amendment to 

IIRB on May 11, 2009, which was approved on May 19, 2009. But the 

amendment approval was granted after two subjects were monitored using the 

two new carbaryl products. This situation was reported to IIRB as a deviation 

on June 16, 2009. IIRB acknowledged the deviation on June 24, 2009 and 

concluded that no further action is required. In EPA’s view, this deviation 

does not raise ethics concerns. Before the subjects used these two products, 

EPA reviewed and approved their use in this study. IIRB had also reviewed 

and approved PRSs for these products, and was aware that these two products 

may be used in the study. The error of not submitting a timely amendment 

was careless, but it is more of an administrative mistake than a substantive 

one. Both EPA and IIRB had approved the addition of the two carbaryl 

products to the list of approved surrogates, and the error of proceeding before 

a protocol amendment had been approved does not raise serious ethics issues. 
Page 17 of 43 

2) The second deviation was that researchers neglected to take photographs of 

the subjects’ clothing after monitoring. This was a deviation from protocol 

Section 12 and SOP AHETF-10.C. This deviation occurred twice, on April 

30, 2009, and May 7, 2009, and was reported to IIRB on May 12, 2009. On 

May 20, 2009, IIRB acknowledged the deviation and concluded that subjects 

were not at increased risk and that no further action was required. This 

deviation does not raise ethics issues. I defer to the EPA science reviewer on 

whether the deviation affects the scientific integrity of the data. 

There was one deviation in the analytical phase of the research that was reported 

to IIRB. This deviation raises no ethical issues, but I defer to the EPA science reviewer 

on whether the deviation affects the scientific integrity of the data. 

4.5.2 Unreported Deviations

There were three unreported deviations during the field phase of AHE59. 

1) All four subjects had instances of touching the cab door, equipment, or other 

treated surfaces while not wearing gloves. There is no record that the 

observer reminded the workers to wear their gloves or that the observer 

reported the behavior to the study director, which violated protocol section 

2.3.2, SOP AHETF-10.C.4, and SOP AHETF-11.E.1. These protocol and 

SOP violations were not reported to IIRB. These deviations are discussed in 

greater detail in sections 8.1 and 10.0 of this review. 

2) Protocol section 7.8 states that “a single MU will be conducted in this study 

from each of the five strata” (Vol 9, p. 201). In the conduct of the study, 

however, two subjects applied amounts from the second stratum (10-17 lbs) 

and no worker applied from the third stratum (18-30 lbs) (Vol 9, p 37). 

3) Three of four subjects in this study failed to spray for a minimum of 4 hours, 

as required in Section 7.8 of the protocol (“Each MU shall consist of a period 

of at least 4 hours of spraying and at least 3 tank loads of the spray mixture.”) 

See Table F in Appendix 2 for individual spray times for each subject. 

Although this protocol deviation should have been reported to IIRB, it raises 

no ethics issues. I defer to the EPA science reviewer on whether this 

deviation raises science issues. 
Page 18 of 43 

Table 2. Summary of Protocol Amendments and Deviations 

Study Deviations 

ID Amendments Field Phase Analytical Phase 

Reported:

1. On two occasions, subjects were selected 

randomly using a coin flip rather than 

drawing names as required in protocol. 

AHE55 1. Amended once to 

incorporate comments 

from EPA and HSRB. 

Study report indicates that 

the protocol was amended 

3 times prior to execution 

of the field phase, however 

it did not summarize these 

changes. 

Unreported:

1. Rather than growers being reimbursed for the 

pesticide as required by section 2.4 of the 

protocol, the Local Site Coordinator 

purchased the product and delivered it to the 

application sites 

2. The witness for the consent process for a 

non-reader was selected by the prospective 

subject, contrary to the protocol requirement 

that the witness should have no association 

with the grower or worker. 

3. One subject touched the cab door while not 

wearing gloves, and later opened the cab door 

with bare hands. There is no record that the 

observer reminded the worker to wear his 

gloves or that the observer reported the 

behavior to the study director, contrary to the 

protocol (section 2.3.2) and SOP AHETF10.C.4. 

4. Four of five subjects did not achieve 

protocol-required 4-hour minimum spray 

time. 

None reported 

AHE56 

1. Amended once to 

incorporate comments 

from EPA and HSRB. 

Study report indicates that 

the protocol was amended 

two times prior to 

execution of the field 

phase, however it did not 

summarize these changes. 

Reported: 

1. The original list of eligible growers was 

exhausted before successfully recruiting 

enough subjects. Two growers ultimately 

monitored as subjects were referred to the 

AHETF by other growers, and did not appear 

on the eligible grower list. This was a 

deviation because the protocol did not 

provide for recruitment beyond the eligible 

growers list. 

2. Informed consent form signed by one subject 

after donning inner dosimeter garment. 

3. Travel fortification samples were not 

prepared until monitoring day 4. 

4. One subject took a bathroom break without 

first washing his hands and having a 

handwash sample taken. 

5. Air flow rotometer measurements taken after 

removal of sampling gear from workers. 

Unreported:

1. None of the 5 subjects achieved the protocolrequired 4-hour minimum spray time. 

1. OVS sampling tubes 

Set 2 was above 15% 

criteria (reported 

22.02%) for backcalculation value at 

5.0 ng/mL standard. 

2. Travel spikes 

analyzed 

inadvertently. 

3. For Set 2a OVS 

samples, 3.0 mL 

aliquot was used 

instead of 4.0 mL 

(deviation reported in 

IIRB correspondence 

[Volume 4], but not 

within Appendix B of 

AHE56 study report 

[Volume 3]). 
Page 19 of 43 

Table 2. Summary of Protocol Amendments and Deviations 

Study Deviations 

ID Amendments Field Phase Analytical Phase 

Reported: 

1. One subject applied 10.68 lbs (1.68 lbs above 

stratum 5-9 lbs); was monitored for 2 hours 

(the protocol prescribes a minimum of 4 

hours of application time); and applied only 2 

tank loads (the protocol prescribes a 

minimum of 3 tank loads). 

AHE57 1. Amended once to 

incorporate comments 

from EPA and HSRB. 

2. Amended purity 

analysis section of the 

protocol (section 

7.5.3). 

Unreported: 

1. Protocol section 7.8 states that “a single MU 

will be conducted in this study from each of 

the five strata” (Vol 5, p. 152). In the 

conduct of the study, however, two subjects 

applied amounts from the second stratum 

(10-17 lbs) and no worker applied from the 

lowest stratum (5-9 lbs) (Vol 5, p 31). 

2. None of the 5 subjects achieved the protocolrequired 4-hour minimum spray time. 

1. Inner dosimeter 

controls and LOQ 

concurrent recovery 

samples were diluted 

to 5 mL while field 

samples were diluted 

to 10 mL. 

2. Protocol lists method 

titles not used. 

3. Aliquot deviation in 

Method ARTF-0001 

for 2-piece cotton 

inner dosimeters. 

4. Back-calculated 

calibration standard 

values for the 0.001 

ug/mL OVS sample 

and the 0.005 ug/mL 

face/neck wipe 

standard deviated 

from the theoretical 

value by > 20%. 

1. Amended once to 

incorporate comments 

from EPA, California 

Department of 

Pesticide Regulation, 

and HSRB. 

2. • 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. 

AHE58 

3. Added a new 

malathion product to 

possible test products 

(the active ingredient 

malathion was 

already an approved 

surrogate) 

Reported: 

1. On study day 2, inner dosimeters were 

inadvertently not folded over after field 

fortifications were conducted and prior to 

covering with cloth as specified in SOP 

AHETF-8.E.5. 

2. Low level field fortifications conducted in 

duplicate on day 4, instead of triplicate. 

3. One subject was monitored for only 3 hours 8 

minutes (protocol prescribes a minimum of 4 

hours of application time). 

4. Field fortifications were done at (known) 

levels different than those specified in 

protocol. 

Unreported: 

1. One subject touched contaminated equipment 

while not wearing gloves. There is no record 

that the observer reminded the worker to 

wear his gloves or that the observer reported 

the behavior to the study director, contrary to 

the protocol (section 2.3.2) and SOP AHETF10.C.4. 

2. Protocol section 7.8 states that “a single MU 

will be conducted in this study from each of 

the five strata” (Vol 7, p. 253). In the 

conduct of the study, however, two subjects 

applied amounts from the highest stratum 

(56-100 lbs) and no worker applied from the 

second stratum (10-17 lbs) (Vol 7, p 43). 

3. At least 1 of the 5 subjects did not achieve 

the protocol-required 4-hour minimum spray 

time. 

1. Concentrations of 

some field 

fortification 

solutions corrected 

for volume based on 

density, not 

gravimetrically, 

resulting in incorrect 

field fortification 

concentrations. 
Page 20 of 43 

Table 2. Summary of Protocol Amendments and Deviations 

Study Deviations 

ID Amendments Field Phase Analytical Phase 

Reported: 

1. Two subjects were monitored using carbaryl 

products before those products were formally 

approved by IIRB for use in the research. 

2. Post-monitoring photographs of worker 

clothing were inadvertently not taken. 

AHE59 1. Amended once to 

incorporate comments 

from EPA and HSRB. 

2. Two carbaryl products 

were added to possible 

test substances 

Unreported: 

1. Each of the four subjects contacted a 

contaminated surface at least one time while 

not wearing gloves. There is no record that 

the observer reminded the worker to wear his 

gloves or that the observer reported the 

behavior to the study director, which violated 

the protocol (section 2.3.2) and SOP AHETF10.C.4. 

2. Protocol section 7.8 states that “a single MU 

will be conducted in this study from each of 

the five strata” (Vol 9, p. 201). In the 

conduct of the study, however, two subjects 

applied amounts from the second stratum 

(10-17 lbs) and no worker applied from the 

third stratum (18-30 lbs) (Vol 9, p 37). 

3. Only 1 out of 4 subjects achieved the 

protocol-required 4-hour minimum spray 

time. 

1. Curve standard off 

by 25.89% more 

than 15% criteria – 

(deviation reported 

in IIRB Corresp. 

Report (Vol 10) but 

not detailed in 

Appendix B of study 

report (Vol 9) 

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 generally followed in all five studies. 

In all studies, an initial grower universe list was generated from published lists or 

databases. Duplicate entries were suppressed and, for AHE55 and AHE56, growers not 

having sufficient acreage were removed, to produce the master grower list. For AHE55, 

the initial list was so large (1,381 names), even after suppression of duplicates and 

growers with less than 10 acres, that the master grower list was a randomly generated 

subsample of 425 contacts. 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 (Vol 

1, p. 31; Vol 3, p. 31; Vol 5, p. 28; Vol 7, p. 39; Vol 9, p. 33) details the number of 

growers/workers in each stage of the recruitment process. 

There was a reported deviation in recruiting for AHE56, when a tropical storm 

struck the day before monitoring was scheduled to begin. The storm necessitated the 

cancellation of the field work for several days. When the research was ready to proceed 
Page 21 of 43 

the following week, three of the six growers were either no longer willing to participate 

or unable to be rescheduled within the necessary timeframe to efficiently conduct the 

research. In order to find the additional two needed growers, the AHETF contacted two 

growers who had been referred to them by other growers on the master grower list, and 

those two growers ultimately participated in the research. This deviation is discussed in 

more detail on page 11 of this review. 

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 

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 AHE55, AHE56, and AHE57, all of the 

area experts that responded to the survey (4/4 for AHE55; 4/4 for AHE56, 5/5 for 

AHE57) agreed that study participants were typical of growers/applicators in the areas 

where the study was performed. For AHE58, four of five area experts agreed the 

growers/applicators were typical, and one stated that she was not familiar enough to 

provide an opinion. In AHE59, three of four area experts that responded to the survey 

opined that the growers/applicators were typical, whereas one responded that the 

monitored growers were not representative because their average farm size was below 

average and they did not use newer spray technologies that apply at lower gallons per 

acre. 

6.0 Consent Process 

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

all studies. The only deviations related to the consent were in AHE55, where the witness 

for a non-reading subject was selected by the subject, contrary to the protocol 

requirement that the subject be unknown to the subject, and in AHE56, where one subject 

donned the inner dosimeter after giving verbal consent but before signing the consent 

form, although he signed the form shortly thereafter. The two deviations are discussed in 

detail in Sections 4.1.2 and 4.2.1 of this review. 

7.0 Subject Demographics 

Demographic information on the monitored subjects is summarized in Table 3 

below. 

7.1 Years of Experience

In AHE55, one worker listed his age as 20 years old, but self-reported that he had 

10 years of experience (Vol 1, p. 32). Likewise, in AHE57, one subject listed her age as 

21 years old, but self-reported that she had 6 years of experience. The unexpectedly large 
Page 22 of 43 

number of years of experience compared with the reported ages of these two subjects 

raises questions about the accuracy of these subjects’ reporting of their age and/or years 

of experience. 

7.2 Health Status

Prospective subjects were asked about their health status during the consent 

process, based on the procedures described in SOP AHETF 11.C.0/11.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 medication 

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

to participate (protocol section 2.1). 

 

7.3 Pregnancy Testing

 There was one female subject in AHE57; there were no female subjects in the 

other studies. Supplement 1 (email from D. Johnson to J. Evans and K. Sherman) 

confirms that the female subject took a pregnancy test, the test showed that she was not 

pregnant, and she stated that she was not nursing. 

Table 3: Subject Characteristics 

Number of Subjects 

AHE55 AHE56 AHE57 AHE58 AHE59 

Males 5 5 4 5 4 

Females 0 0 1 0 0 

Preferred consent process in 

English 4 Not reported 5 3 4 

Preferred consent process in 

Spanish 1 Not reported 0 2 0 

Self-identified as non-reader 

and used witness 

1 

(in English) 0 0 0 0 

Employment 

 Farm Employee 5 0 2 3 3 

 Farm Owner 0 4 3 0 1 

 Commercial Applicator 0 1 0 2 0 

Years of Experience 3-48 7-44 6-50 7-28 5-40 

Age Range 20-70 43-68 21-58 27-49 26-62 

Requested Results 5 5 5 4 4 

Withdrew 0 0 0 0 0 

Removed from participation 

by AHETF 0 0 0 0 0 
Page 23 of 43 

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 Instances of Failure to Wear Gloves

In AHE55, AHE58, and AHE59, the field notes report instances in which a 

subject, who was outside of his enclosed cab, contacted surfaces contaminated with 

pesticide residues while not wearing chemical-resistant gloves. 

Below in Table 4 are the log entries, prepared by the study observers in each of 

the studies, documenting the observations of instances in which a subject contacted a 

contaminated surface while not wearing gloves. 

Table 4. Observations Noting Instances of Failure to Wear Gloves 

Study ID MU 

ID 

Log 

Time Observation 

11:44 “...exits cab without gloves...shuts the door...contacting the side edge.” AHE55 A3 12:14 “...opens door with bare hands...” 

AHE58 A5 08:14 “Turned off water near tank with bare hand...” 

A1 08:58 “Climbed back into cab, opened door with bare hands.” 

A2 Gen. 

obs. “Door opened with bare hand.” 

A3 09:56 “Opened truck door with bare hands...” 

11:02 “...exited cab and with bare hands picked up a marker from ground...” 

13:20 “Exited cab, walked back to sprayer and with bare hands, turned lever...” 

14:32 “Walked to front of spray tank and with bare hand turned lever...” 

AHE59 

A4 

15:49 “...walked back to sprayer and with bare hands, turned off a couple 

nozzles...” 

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. . . . 
Page 24 of 43 

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 4 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. There was one female subject; 

she tested negative for pregnancy and confirmed that she was not nursing. 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. This research would not comply with Subpart L if any of the 

subjects was a child, or a pregnant or nursing woman. The study reports document 

compliance with subpart L. 

 10.3.1 Subjects not wearing gloves when contacting treated 

 surfaces

Based on the study report, I find that the AHETF violated the protocol by not 

ensuring that all study participants wore label-specified PPE when they contacted 

surfaces contaminated with pesticide residues. As summarized in Table 4, the log for 

AHE55 reports that there was one subject (A3), who exited and contacted contaminated 

surfaces twice. The log for AHE58 reports that there was one subject who exited and 

contacted a contaminated surface one time. The log for AHE59 reports that there were 

three subjects, each of whom exited and contacted a contaminated surface one time, as 
Page 25 of 43 

well as one subject (A4), who exited and contacted contaminated surfaces at least four 

times. 2 

In addition to the failure to enforce the use of PPE, as required by section 2.3.2 of 

the protocol, there is no documentation indicating that the observer(s) notified the study 

director, principal field investigator, or quality assurance unit of any of these occurrences 

as required by section 6.12 of SOP AHETF-10.C.4. Finally, the study reports do not 

indicate that any of these subjects were reminded by the observer of the gloves 

requirement. The failure to warn the subjects would also violate SOP AHETF-11.E.1 if 

deemed a “safety issue.” 

As noted above, section 2.3.2 of the study protocols provides that the AHETF will 

“enforc[e] the use of label-specified PPE (especially the use of gloves outside the cab if 

contacting contaminated surfaces) during participation.” Two of the SOPs also contain 

language relevant to this situation. SOP AHETF-10.C.4 states: 

Section 6.12: “Observers should contact the Study Director, PFI or QAU if they 

observe any activity contrary to the study design, label requirements, or 

dangerous activities undertaken by the worker. Based on the event, the SD has the 

discretion to terminate the MU.” 

AHETF-11.E.1 states: 

Section 3.3: “During the study conduct, researchers will ensure compliance with 

safety requirements on the product label and with the Worker Protection Standard 

(WPS). For example, workers will be reminded to use the label specified PPE and 

to follow use directions on the label 

“a. Each worker will be observed by a researcher during the entire 

 monitoring period unless the worker travels out of sight of the 

 observer (e.g., aerial application, driving beyond view in a field). 

 2 In examining the records, EPA has determined that none of the subjects violated either the 

labeling of the pesticides or EPA’s Worker Protection Standard (WPS). The WPS states at 40 CFR 

170.240(d)(5)(iv): 

“persons occupying an enclosed cab shall have all labeling-specified personal protective 

equipment immediately available and stored in a chemical-resistant container, such as a plastic 

bag. They shall wear such personal protective equipment if it is necessary to exit the cab and 

contact pesticide-treated surfaces in the treated area. Once personal protective equipment is 

worn in the treated area, it must be removed before reentering the cab.” 

The WPS requires gloves when contacting “pesticide-treated surfaces,” whereas the protocol refers to 

“enforcing the use of label-specified PPE (especially the use of gloves outside the cab if contacting 

contaminated surfaces) during participation.” In EPA’s view, all of the surfaces contacted by subjects not 

wearing gloves (summarized in Table 4) were “contaminated” with pesticide residues, but, for WPS 

compliance purposes, were not “pesticide-treated surfaces.”
Page 26 of 43 

“b. Worker observers will not advise workers on how to perform their 

work unless a safety issue is involved. If the observer advises a worker 

about a safety issue and the worker does not comply, the observer will 

then immediately notify the Study Director and ask the worker to 

cease any activity.” 

 In sum, the behavior of the research team related to the instances of subjects not 

wearing gloves violates section 2.3.2 of the protocol, section 6.12 of SOP AHETF10.C.4, and possibly section 3.3 of SOP AHETF-11.E.1. Specifically: 

1) The use of “label-specified PPE (especially the use of gloves outside the cab if 

contacting contaminated surfaces)” was not enforced, as required in section 2.3.2 

of the protocols. 

2) There is no documentation indicating that the observer(s) notified the study 

director, principal field investigator, or quality assurance officer of the label 

violations, as required by section 6.12 of SOP AHETF-10.C.4. 

3) There is no documentation indicating how observers determined whether they 

needed to advise the non-glove-wearing workers to wear their gloves, as required 

by section 3.3 of SOP AHETF-11.E.1. 

These protocol and SOP violations are deviations that should have been immediately 

reported to IIRB. The AHETF did not report these deviations. 

10.3.2 Considerations regarding the compliance of AHE55, AHE58, 

and AHE59 with Subparts A through L

This section addresses additional considerations that I regard as relevant to 

making a decision about whether, in light of the deviations discussed in Section 8.1 

related to glove usage, the reported research was “conducted in substantial compliance 

with subparts A through L” of 40 CFR part 26. See 40 CFR 26.1705. 

The ethical duty to warn arising from the principle of beneficence. There is a 

recognized ethical obligation on researchers to intervene when they become aware of 

behavior of a participant in human research that endangers the safety of the subject. 

Under the prevailing understanding of the ethical principles governing the conduct of 

human research, a researcher has a duty to warn subjects and/or intervene when the 

subjects engage in behavior potentially dangerous to themselves. This duty arises from 

the principle of beneficence from the Belmont Report, which obligates the researcher to 

secure the well-being of all research participants and protect participants from harm while 

the research is being conducted. The safety of the subjects must be prioritized above the 

desire to gather data. In making my determination about the ethical acceptability of the 

reported research, I considered the following factors. 

 
Page 27 of 43 

Intent of the investigators. There is no evidence to indicate that the investigators 

intended to place the participants at risk. In fact, all of the available information indicates 

the opposite, that the investigators were concerned about and took steps to reduce risks to 

the participants. These include their overall responsiveness to EPA’s and the HSRB’s 

comments and the concrete steps they took to minimize risks to subjects including: 

• Selecting only experienced pesticide handlers 

• Requiring experience operating the equipment to be used 

• Reminding workers of safe chemical handling practices 

• Identifying nearby hospitalization facilities in case of emergency 

• Monitoring the heat index and stopping the study if conditions warrant 

• Providing transportation to medical treatment and covering the costs of 

• Treatment, if needed 

• Having a medical professional on site to observe the workers and, if needed, to 

provide urgent care 

• Observing study participants throughout the monitoring period 

• Ensuring that all tank mix products were used according to approved label (s) and 

did not require any additional PPE. 

The extent to which the ethical deficiency jeopardized (or could have jeopardized) 

the subjects’ safety. By not intervening during the study, the investigators allowed 

certain subjects to continue to engage in behaviors that increased their exposure and thus 

their risk. There was some variety in both the kind of conduct and the frequency of the 

conduct that observers reported. For four of the workers (one in AHE55; three in 

AHE58), the behavior involved only a very brief contact with a contaminated surface 

(e.g. removing gloves before rather than after entering the closed-cab, or touching the 

door handle while not wearing gloves) and likely did not measurably increase exposure. 

In other instances, the behavior was of a nature that the subject was likely getting a 

measurable increased increment of exposure to his hands (i.e., subject A4 in AHE59 who 

was not wearing gloves while contacting items on the ground [milk carton, rock]) that 

were likely contaminated with freshly applied residues). Four workers only had one 

instance each where they were observed contacting a treated surface without gloves, one 

worker had two instances, and one worker had at four. None of the subjects’ 

actions were atypical of the behavior that EPA would expect pesticide applicators to 

exhibit. The gradations of violations and the likely impact of the violations on the levels 

of exposure make it difficult for an observer to determine which, if any, of the behaviors 

would have risen to a point triggering the duty to intervene. It is worth noting that none 

of the subjects reported any discomfort or symptoms of illness. Further, although it could 

not have been known at the time, EPA analysis of the levels of exposure received by the 

individual subjects showed that all of them had acceptably safe levels of exposure. 

The extent to which the investigators knew or should have known how they should 

have responded. As discussed above, observers noted a variety of actions that ranged 

from very brief contacts with contaminated surfaces to more serious and repeated 

instances of contact with contaminated surfaces. While the applicable sections of the 

SOPs describe a general obligation to ensure study subjects follow applicable safety 

requirements and otherwise ensure they avoid dangerous practices, the directions lack 
Page 28 of 43 

specificity with respect to what kinds of behavior raises a “safety issue” triggering the 

requirement to provide a warning and/or halt the research. The researchers could quite 

reasonably have thought that they had and should exercise judgment about whether and 

how to address instances of subject noncompliance. Certainly, until now, neither EPA nor 

the HSRB has focused on the application of the protocol and SOPs to the kinds of 

situations described in this report. 

10.3.3 Conclusion regarding the compliance of AHE55, AHE58, and 

AHE59 with Subpart K

I have determined that the researchers failed to follow the protocol and the SOPs 

in several different ways and on multiple instances, as discussed above. I identified a 

number of unreported deviations which were of a minor or technical nature. This reflects 

a lack of thoroughness on the part of the AHETF in comparing the actual conduct of the 

research with the requirements of the protocol. In the future, EPA will expect the 

AHETF to examine field reports for possible deviations and to report them promptly to 

the supervising IRB. Apart from the gloves deviations discussed in Section 10.3.1 above, 

I identified no other noteworthy deficiencies in the ethical conduct of these five studies. 

The protocols were faithfully executed, properly amended when necessary, and only one 

amendment was not approved by the overseeing IRB before it was implemented. The 

reported and unreported deviations are of the nature to be expected in complicated field 

research of this kind, and did not affect the welfare or safety of the subjects, or 

compromise their informed and voluntary consent. 

Of the unreported deviations, I am most concerned that the observer(s) did not 

ensure that the subjects wore their gloves as required by the protocol, and that the 

observers did not alert the study director about these incidents and appear not to have 

advised the subjects to wear gloves. These violations resulted in some, generally minor 

increased exposure and increased risk for the subjects. In addition, the protocol and SOP 

deviations should have been promptly reported to IIRB. Failure to report deviations 

prevents the IRB from exercising oversight and making recommendations for corrective 

action. It is my view, however, that despite these violations, the research substantially 

complied with the applicable regulations. 

With respect to evaluating the failure to ensure that subjects wore gloves against 

the requirements of subpart K, I find that the researchers’ violation consisted of a failure 

to report the deviations from the protocol pursuant to the rules of IIRB. While this failure 

to report is not strictly a violation of the regulations, it is inconsistent with the intended 

protections of the rule (See 40 CFR 26.1108). As discussed above, I do not think the 

failure to report the deviations placed the subjects at significant risk. Further, there is no 

evidence of any attempt by the researchers to evade IRB review and oversight, and the 

researchers have a long and consistent history of instituting corrective actions when EPA 

and the HSRB identifies ethical deficiencies. Consequently, I think that there is 

sufficient information to conclude the researchers’ conduct with respect to subjects’ 

failure to wear gloves substantially complied with subpart K. 
Page 29 of 43 

With respect to whether the research was deficient under the more general ethical 

duty to warn or otherwise intervene to protect the safety of study participants, I note that 

neither EPA nor the HSRB has provided the researchers with guidance on their 

responsibilities under this ethical principle. Further, in assessing their actions, I note that 

the subjects’ behavior was not plainly dangerous. In most cases, a subject failed to wear 

gloves only on a single occasion. While a warning might have helped to protect these 

subjects from additional higher exposure, the degree of increased exposure actually 

experienced by these subjects was quite minor. As for subject A4 in study AHE59, the 

subject who repeatedly failed to wear his gloves, I think it would have been reasonable 

for the research team also to conclude the subject’s actions, although concerning, were 

not so dangerous that they required special warnings or intervention, such as termination 

of his participation in the study. This applicator’s actions did not involve prolonged 

contact with pesticide treated surfaces and are not atypical of the behavior of at least 

some pesticide applicators. Certainly, there was no indication that any of the participants 

experienced any physical distress during the research. Finally, EPA’s post hoc risk 

assessment, finding an acceptable level of exposure for all study subjects, supports the 

reasonableness of a judgment that the behavior of subjects, including A4, was not overly 

risky. In sum, in view of the researchers’ likely understanding of their ethical duties and 

a reasonable view of the dangers posed by the subjects’ behavior, I cannot find that the 

researchers violated the principle of beneficence in this study. 

Taking into account the overall care with which the research was defined and 

conducted, these deficiencies noted in the conduct and documentation of the research fall 

far below the level of substantial non-compliance with subparts A through L of 40 CFR 

part 26. I conclude that 40 CFR §26.1705 does not prohibit EPA reliance on this study. 

10.4 Compliance with 40 CFR §26 subpart M 

As is documented in Attachment 3 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 
Page 30 of 43 

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-E) 

Attachment 2: Time Spent Spraying (Table F) 

Attachment 3: §26.1303 completeness checks 

Attachment 4: Responsiveness to EPA and HSRB Comments on protocols (Tables G, H)
Attachment 1 

Ethics-Related Study Chronologies 

Page 31 of 43 

Table A: AHE55 

Date 

06/24-25/08 HSRB reviewed protocol and approved with recommendations 

07/11/08 Phase 1 recruiting (creation of grower list). 7/11/08 to 9/2/08 

07/18/08 Submitted documents to IIRB to amend protocol, consent form, and product risk 

statements (following June 2008 HSRB meeting) 

07/21/08 IIRB approves revised documents 

07/28/08 Protocol finalized and signed by Study Director 

09/03/08 Phase 2 recruiting (calls to grower list). 9/3/08 to 10/7/08 

10/08/08 Phase 3 recruiting (site visits and participant selection) - 10/8/08 to 

10/26/08 

10/27/08-

10/31/08 

Five subjects monitored 10/27/08 – 10/31/08 

11/16/08 Protocol Deviation 1 reported to IIRB [see Volume 2, pp. 21-220] 

• Deviation occurred 10/28/08, 10/30/08 

• On two occasions, subjects were selected by flipping a coin to select a worker to 

participate from among two possible workers, rather than by drawing names from a 

container as described in the protocol 

11/17/08 IIRB concludes Protocol Deviation 1 did not place subjects at increased risk; no further 

action required 

03/02/09 Annual progress report submitted to IIRB 

03/03/09 IIRB approves ongoing research; extends approval of research from 3/3/09 to 3/2/10 

02/04/10 Close out report submitted to IIRB 

02/04/10 IIRB accepts Study Completion Report; study considered closed 
Attachment 1 

Ethics-Related Study Chronologies 

Page 32 of 43 

Table B: AHE56 

Date 

06/24-25/08 HSRB reviewed protocol and approved with recommendations 

07/11/08 Phase 1 recruiting (creation of grower list). 7/11/08 to 7/24/08 

07/18/08 Submitted documents to IIRB to amend protocol, consent form, and product risk 

statements (following June 2008 HSRB meeting) 

07/21/08 IIRB approves revised documents 

07/24/08 Protocol finalized and signed by Study Director 

07/24/08 Phase 2 recruiting (calls to grower list). 7/24/08 to 9/04/08 

08/08/08 Phase 3 recruiting (site visits and participant selection) - 8/8/08 to 

8/23/08 

8/25/08 Five subjects monitored 08/25/08 – 08/28/08 

09/05/08 Protocol Deviation 1 reported to IIRB [see Volume 4, pp. 227-231] 

• Two growers whose names did not appear on the list of eligible growers were referred 

to investigators. The two referred subjects volunteered, were selected, and were 

monitored as subjects. 

09/15/08 IIRB concludes Protocol Deviation 1 did not place subjects at increased risk; no further 

action required 

09/17/08 Protocol Deviations 2, 3 reported to IIRB [see Volume 4, pp. 232-238] 

• Deviation 2 occurred on 8/18/10 

- One subject was dressed in his inner dosimeter before signing his informed 

consent form 

• Deviation 3 (three different deviations) occurred between 8/18/10 and 8/21/10 

- Deviation: Travel fortification samples were not prepared until monitoring day 4. 

- Deviation: During monitoring, a subject stepped away from the tractor to relieve 

himself behind a tree while the spray tank was being re-filled. He was out of sight 

of the observer at the time. After the deviation was recognized, the observer 

reminded the worker that he should follow label user safety recommendations, 

“users should was hands before...using the toilet.” This was also a deviation from 

AHETF SOP 8.B.4, section 5.2, which requires hand samples to be collected prior 

to workers using the restroom. 

- Deviation: Air flow rotometer measurements were taken after removal of sampling 

gear from workers; this is a deviation from AHETF SOP 8.D.2, section 4.11. 

09/23/08 IIRB concludes Protocol Deviations 2, 3 did not place subjects at increased risk; no further 

action required 

01/02/09 Analytical phase deviations reported (dated 12/16/10) reported to IIRB [see Volume 4, 

pp. 239-244]

• Deviation: The back-calculation value for the second lowest standard at 5.0 ng/mL 

was +22.02%, which does not meet the ±15% acceptance criteria in Protocol AHE56, 

Section 15.3. 

• Deviation: The two travel spikes were analyzed along with the other field spikes. This 

deviates from Protocol AHE56, Section 11.1 where it states the travel spikes are only 

analyzed if deemed necessary by the Study Director. 

• Deviation: For analysis of carbaryl in OVS air sampling tubes, Set 2a, a 3.0 mL 

aliquot was process through the method rather than a 4.0 mL aliquot, which then 

required a 0.6 mL (instead of 0.8 mL) final volume for HPLC analysis. This was a 

deviation from AHETF Analytical Method ARTF-AM-013, Revision #1. 

01/07/09 IIRB concludes no further action required on protocol and method deviations dated 

12/16/08 and reported on 1/02/09 

03/03/09 Annual progress report submitted to IIRB 

03/10/09 IIRB approval of ongoing research 

02/15/10 Close out report submitted to IIRB 

02/19/10 IIRB accepts Study Completion Report; study considered closed 
Attachment 1 

Ethics-Related Study Chronologies 

Page 33 of 43 

Table C: AHE57 

Date 

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

01/16/09 Submitted documents to IIRB to amend protocol, consent form, and product risk 

statements (following June 2008 HSRB meeting) 

01/19/09 IIRB approves revised documents 

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

01/26/09 Phase 1 recruiting (creation of Master Grower List and Qualified Grower List). 1/26/09 to 

3/5/09 

02/17/09 Phase 2 recruiting (calls to grower list). 2/17/09 to 4/2/09 

4/02/09 Phase 3 recruiting (site visits and participant selection) – 4/2/09 to 

5/22/09 

5/15/09 Subjects monitored 5/15/09 to 5/22/09 

6/4/09 Protocol Deviation 1 reported to IIRB [see Volume 6, pp. 105, 106, 110, 111] 

• Deviation occurred 5/22/09 

• The subject assigned to Stratum 1 (5.0 lbs a.i. to 9.0 lbs a.i.) sprayed 10.68 lbs a.i., 

which exceeded the stratum limit of 9.0 lbs a.i. In addition, this subject applied only 

2 tank loads for a period of 2 hours, whereas section 7.8 of the protocol states that 

each subject shall spray at least 3 tank loads of spray mixture over a period of at least 

4 hours. 

6/7/09 AHETF submits to IIRB an Amendment to the purity analysis section of the protocol 

(Section 7.5.3) [see Volume 6, pp. 107-109, 170-172]

• This Amendment was emailed to IIRB on 6/7/09, but it was not immediately 

acknowledged by IIRB 

• In September 2010, after the study was closed, AHETF requested copies of IIRB’s 

records on the Amendment, and was informed at that time that IIRB did not have a 

record of the Amendment. 

• On 9/14/10, IIRB acknowledged receipt of the Amendment after study closure, and 

noted that the change was “administrative in nature, did not affect subject safety, and 

would not have received a revision to the consent form.” 

6/10/09 IIRB concludes no further action required on Protocol Deviation 1 

7/15/09 IIRB provides notification of risk of study closure 

7/16/09 Progress report submitted to IIRB 

8/04/09 IIRB approves ongoing research; extends approval of research from 8/04/09 to 8/03/10 

7/07/10 Problems in Research Report submitted to IIRB for review [see Volume 6, pp. 134-141, 

144-145] 

• Reports four deviations from analytic procedures methodologies that occurred on 

2/25/10, 3/1/10, 3/4/10, and 4/9/10. 

7/08/10 IIRB notifies AHETF of risk of study closure 

7/13/09 IIRB concludes no further action required on the four analytical protocol deviations 

reported on 7/7/09 

07/21/10 Close out report submitted to IIRB 

07/23/10 IIRB accepts Study Completion Report; study considered closed 
Attachment 1 

Ethics-Related Study Chronologies 

Page 34 of 43 

Table D: AHE58 

Date 

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

03/26/09 Submitted changes to protocol, consent form, California Bill of Rights , recruitment flyer, 

and product risk statements (following June 2008 HSRB meeting) 

04/01/09 IIRB approves revised recruitment flyer 

4/06/09 IIRB approves revised informed consent document, California Bill of Rights, and product 

risk statements 

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

04/21/09 Phase 1 recruiting (creation of Master Grower List and Qualified Grower List). 4/21/09-

7/27/09 

05/12/09 Phase 2 recruiting (calls to qualified growers). 5/12/09 to 8/14/09 

6/01/09 Phase 3 recruiting (site visits and participant selection). 6/01/09 to 

8/09/09 

6/19/09 Amendment 1 submitted to IIRB 

• Amend inclusion criteria to allow participation of workers who normally wear two 

layers of clothing 

• Amend protocol to allow recruitment in any county in California or Washington 

• Remove the efficient configuration requirement if recruitment area is expanded 

6/23/09 Amendment 1 approved by IIRB 

6/26/09 Two subjects monitored, 6/26/09 and 7/01/09 

7/14/09 IIRB provides notification of risk of study closure 

7/16/09 Progress report submitted to IIRB 

7/22/09 Amendment 2 (adding one malathion product) submitted to IIRB 

7/22/09 Amendment 2 approved by IIRB 

07/25/09 Supplemental information for progress report submitted to IIRB 

07/28/09 Subject monitored 

07/29/10 IIRB approves ongoing research; extends approval of research from 7/28/09 to 7/27/10 

08/07/09 Two subjects monitored, 08/07/09 and 08/10/09 

9/02/09 Protocol Deviations 1, 2, 3 reported to IIRB (deviations occurred 7/6/2009, 8/11/09, and 

8/11/09) [see Volume 8, pp. 307-314] 

• Deviation 1: Whole body dosimeter fortification samples not folded before covering 

• Deviation 2: Some low level fortifications done in duplicate instead of triplicate on 

one day 

• Deviation 3: Monitoring time for subject A5 was less than 4 hours 

9/03/09 IIRB acknowledges Deviations 1, 2, and 3; no further action required 

12/7/09 AHETF submits to IIRB Deviation 4 (deviations occurred 6/10/09 and 6/11/09) [see 

Volume 8, pp. 315-318]

• Some field fortification samples were incorrectly prepared in the laboratory, so the 

fortification levels were not correct. However, the researchers know the actual 

amounts fortified, so no field fortification samples are missing. 

12/15/09 IIRB acknowledges Deviation 4; concludes no further action required 

2/24/10 IIRB provides notification of risk of study closure 

02/21/10 Close out report submitted to IIRB 

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

4/19/10 Two deviations reported to IIRB [see Volume 8, pp. 354-357]

• Field phase: Calculations were performed incorrectly in preparation of field 

fortification samples. The solution was prepared using volume corrected for density 

instead of gravimetrically. 

• Analytical Phase: Concentrations of some field fortification solutions corrected for 

volume based on density, not gravimetrically, resulting in incorrect field fortification 

concentrations. 

4/20/10 IIRB acknowledges two deviations that were reported after study closure 
Attachment 1 

Ethics-Related Study Chronologies 

Page 35 of 43 

Table E: AHE59 

Date 

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

01/16/09 Submitted documents to IIRB to amend protocol, consent form, and product risk 

statements (following June 2008 HSRB meeting) 

01/19/09 IIRB approves revised documents 

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

01/26/09 Phase 1 recruiting (creation of Master Grower List and Qualified Grower List). 1/26/09 to 

3/5/09 

02/06/09 Phase 2 recruiting (calls to grower list). 2/06/09 to 3/28/09 

3/30/09 Phase 3 recruiting (site visits and participant selection) – 3/30/09 to 

5/30/09 

4/30/09-

5/09/09 

4 Subjects monitored on 4/30/09, 5/07/09, 5/08/09, 5/09/09 

5/11/09 Protocol Amendment 1 and Deviation 1 submitted to IIRB [see Volume 10, pp. 140-152] 

• Amendment 1: Adding 2 carbaryl products were added to the protocol 

• Deviation 1: No photographs were taken of the subjects after monitoring, in violation 

of SOP AHETF-10.C.4 

5/19/09 IIRB approves Amendment 1 

5/20/09 IIRB acknowledges Deviation 1; concludes no further action necessary 

6/16/09 Protocol Deviation 2 submitted to IIRB [see Volume 10, pp. 153-156]

• Deviation was the use by two monitored subjects of carbaryl products not previously 

approved by IIRB (deviation occurred on 5/07/09 and 5/09/09) 

6/24/09 IIRB concludes no further action required on Protocol Deviation 2 

7/14/09 IIRB provides notification of risk of study closure 

7/16/09 Progress report submitted to IIRB 

7/29/09 IIRB approves ongoing research; extends approval of research from 7/28/09 to 7/27/10 

02/22/10 Close out report submitted to IIRB 

02/25/10 IIRB accepts Study Completion Report; study considered closed 
Attachment 2 

Time Spent Spraying 

Page 36 of 43 

Table F. Amount of Time Reported Spraying (in Minutes) 

MU ID AHE55 AHE56 AHE57 AHE58* AHE59 

A1 192 107 68 [345] 195 

A2 78 179 117 [299] 77 

A3 208 159 142 [255] 156 

A4 178 151 201 [360] 384 

A5 331 166 218 [188] --- *AHE58 spray times could not be determined from observation log. Dermal monitoring times are provided in the 

column for AHE58, as a substitute for spray time. Spray time is shorter than monitoring time, so AHE58/A5 clearly did 

not spray for 4 hours. It is unclear if the other MUs in AHE58 sprayed for at least four hours. 

Section 7.8 of the protocol states that: “Each MU shall consist of a period of at least 4 

hours of spraying and at least 3 tank loads of the spray mixture.” 

Table F shows the number of minutes for which the subjects operated their sprayers. 

This time included moving from one application site to another with a tank of spray, but 

did not include break time or time spent mixing and loading and driving between the 

application site and the mixing/loading station. 

Gray shading highlights the subjects who did not operate their sprayers for at least 4 

hours, as required in Section 7.8 of the protocol. Only two of the 19 subjects for which 

spray time could be determined had their spray equipment on for “at least 4 hours.” 
Attachment 3 

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

AHE55 (MRID 48303503 )

Page 37 of 43 

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 

§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; 

Approved English CFs: 

p 259 

Approved Spanish CFs: 

 272 

Progress Rpt 223 

Close Out Report 287 

§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. 

N All post-HSRB IIRB reviews were 

under expedited procedures; no 

minutes were made. 

§1115(a)(3): Records of continuing review activities. Y 220, 223, 287 

§1115(a)(4): Copies of all correspondence between the IRB and the investigators. Y 13-287 

§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 

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

required by § 26.1116(b)(5). n/a 

(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 

§1125(a) 

A discussion of: 

(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 61-214 

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

advertisements proposed to be used. Y Flyers & Ads in English & Span 

§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 13-287 

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

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

§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 163 

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

§26.1117, but not identifying any subjects of the research Y 259-268 English 272-281 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 3 

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

AHE56 (MRID 48303504)

Page 38 of 43 

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 

§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; 

Approved English CF:167 

Approved Spanish CF: 188 

Progress report 246 

Close-out report 294 

§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. 

N All post-HSRB IIRB reviews were 

under expedited procedures; no 

minutes were made. 

§1115(a)(3): Records of continuing review activities. Y Progress report 246 

§1115(a)(4): Copies of all correspondence between the IRB and the investigators. Y 16-295 

§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 

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

required by § 26.1116(b)(5). n/a 

(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 

§1125(a) 

A discussion of: 

(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 English versions 140 

Spanish versions 188 

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

advertisements proposed to be used. Y Approval of Flyers & Ads in English & Spanish 218 

§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 16-295

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

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

§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 224-225 

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

§26.1117, but not identifying any subjects of the research Y 251-259 English No Spanish speakers enrolled 

(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 

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

AHE57 (MRID 48289608)

Page 39 of 43 

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 

§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; 

English 80, Spanish 90 

Progress report 115 

Close-out report 147 

§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. 

N 155-164 

§1115(a)(3): Records of continuing review activities. Y 105-145 

§1115(a)(4): Copies of all correspondence between the IRB and the investigators. Y 13-172 

§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 157 

§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 

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

required by § 26.1116(b)(5). n/a 

(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 

§1125(a) 

A discussion of: 

(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 Addressed in protocol 

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

advertisements proposed to be used. Y Addressed in protocol 

§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 13-172 

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

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

§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 Approval of all submitted 

documents 79 

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

§26.1117, but not identifying any subjects of the research Y English 120 

No Spanish speakers enrolled 

(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 

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

AHE58 (MRID 48289609)

Page 40 of 43 

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 

§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; 

English 151, Spanish 176 

Progress report 242 

Close-out report 320 

§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. 

N Some approvals under expedited 

review, minutes on progress 

report 300 

§1115(a)(3): Records of continuing review activities. Y 301-318 

§1115(a)(4): Copies of all correspondence between the IRB and the investigators. Y 17-357 

§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 302 

§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 

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

required by § 26.1116(b)(5). n/a 

(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 

§1125(a) 

A discussion of: 

(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 Addressed in protocol 

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

advertisements proposed to be used. Y Addressed in protocol 

§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 17-357 

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

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

§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 Approval of all submitted 

documents 149 

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

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

English 257 

Spanish 286 

(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 

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

AHE59 (MRID 48289610)

Page 41 of 43 

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 

§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; 

English 90, Spanish 77 

Progress report 159 

Close-out report 193 

§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. 

N 184-188 

§1115(a)(3): Records of continuing review activities. Y 140-182 

§1115(a)(4): Copies of all correspondence between the IRB and the investigators. Y 14-195 

§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 189 

§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 

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

required by § 26.1116(b)(5). n/a 

(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 

§1125(a) 

A discussion of: 

(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 Addressed in protocol 

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

advertisements proposed to be used. Y Addressed in protocol 

§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 14-195 

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

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

§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 Approval of all submitted 

documents 74 

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

§26.1117, but not identifying any subjects of the research Y English 164 No Spanish speakers enrolled 

(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 4 

Responsiveness to Major EPA and HSRB Comments 

Page 42 of 43 

Table G. Responsiveness to Major EPA and HSRB Comments on Protocols for AHE55, AHE56 

(reviewed at the June 2008 HSRB Meeting)

EPA or HSRB Comment Addressed before executing 

AHE55, AHE56? 

Addressed before executing 

AHE57, AHE58, AHE59? 

1. Characterize subject representativeness Yes, information gathered for 

AHE55 and AHE56 

Yes, information gathered for 

AHE57, AHE58, and AHE59 

2. Disallow participation by employees of 

Local Site Coordinator 

Yes Yes 

3. Use bilingual researchers rather than 

interpreters 

Yes Yes 

4. Explain how Study Director will determine 

understanding of subjects in consent 

interviews conducted in Spanish 

Yes Yes 

5. Provide toll-free English and Spanish 

information numbers 

Yes Yes 

6. Capture ethnicity and sex of participating 

workers 

Yes Yes 

7. Clarify intended purpose of photos/videos Yes Yes 

8. Minimize identifiable photos/videos Yes Yes 

9. Refer to “AHETF” consistently vice 

“AHETF” and “Sponsor” 

Yes Yes 

10. Drop reference to “cognitively impaired” 

from recruitment flyer 

Yes Yes 

11. Change “liquid pesticides” to “airblast 

application of liquid sprays” 

Yes Yes 

12. Minimize paraphrasing of SOPs in 

protocols 

No Yes 

13. Simplify submissions No Yes 

14. Explain voluntary nature of participation at 

the beginning of consent forms 

No No, but has been addressed in 

subsequent protocols 

15. Ensure accurate Spanish translations No No, but has been addressed in 

subsequent protocols 

16. Update SOPs to: 

• Insure all materials provided to 

candidates are approved by IRB 

• Insure label and MSDS summaries are 

approved by IRB 

• Clarify role of impartial witness to 

consent interviews with non-readers 

• Replace references to WIRB with 

generic references 

• Account for number of workers 

associated with each grower 

• Define processes of diversity selection 

of growers and construction of an 

efficient configuration of MUs in a 

new SOP 

No Yes 

17. Better justify judgments of infeasibility of 

incorporating additional elements of 

random selection 

No No, but has been addressed in 

subsequent protocols 

18. Considering restriction to monitoring no 

more than one worker per employer 

Only 1 worker monitored per 

employer. Restriction added in 

subsequent protocols. 

Only 1 worker monitored per 

employer. Restriction added 

in subsequent protocols. 
Attachment 4 

Responsiveness to Major EPA and HSRB Comments 

Page 43 of 43 

Table H. Responsiveness to Major EPA and HSRB Comments on Protocols for AHE57, AHE58, AHE59 

(reviewed at the October 2008 HSRB Meeting)

EPA or HSRB Comment Addressed before executing 

AHE57, AHE58, AHE59? 

Addressed in subsequent 

AHETF protocols? 

1. Characterize representativeness of 

subjects 

Yes 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. 

Yes 

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 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 

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. 

Yes. 

5. Revise subject recruitment plan to 

specifically address the probability that 

subjects may also be growers. 

No Yes; relevant SOP revised 

6. Remove risks of agricultural work from 

the listing of risks related to the research. 

Yes Yes 

7. Identify risks of pesticide products that 

are due to scripting. 

Yes Yes