AHETF Scenario Design and 

Field Study Protocols:

Closed System Loading of Liquids (CSLL) 

in Non-Returnable Containers 

and 

1

Jeff Evans

Kelly Sherman

Office of Pesticide Programs

and 

CSLL in Returnable Containers
Overview

 The proposed research will measure 

exposure of workers loading liquids using 

closed systems into pre-mix tanks or 

application tanks 

Closed systems are designed to enclose the 

2



pesticide to prevent it from contacting 

handlers

 Closed systems are defined in EPA’s Worker 

Protection Standard as those that “enclose 

the pesticide to prevent it from contacting 

handlers or other persons”
Overview 

 Two scenarios: 

 Loading from non-returnable containers

 Loading from returnable containers

 Exposure will be monitored while subjects 

are mixing and loading (and rinsing, if 

applicable)

 Subjects will not be applying; exposure 

from application will be covered by other 

AHETF scenarios

3
What’s Familiar about this Proposal?

 Design objectives and rationale are 

similar to several previous AHETF 

scenarios reviewed by the HSRB

4

 Protocol procedures related to ethical 

conduct are similar
AHETF Scenario Designs: Closed 

System Loading Liquids (CSLL) 

in Non-Returnable Containers 

and 

CSLL in Returnable Containers 

Science Assessment

5

Jeff Evans

Health Effects Division
Scenario Definition(s) 

 Exposure of individuals involved in Closed System 

Liquid Loading (CSLL) as defined by container type: 

non-returnable (NR) and returnable (R)

 The two scenarios do not involve applying. 

Application is covered by other AHETF scenarios

6

 Based on the use of CSLL systems that are 

consistent with the intent of the Worker Protection 

Standard (WPS): 

 “...designed by the manufacturer to enclose the pesticide 

to prevent it from contacting handlers or other people 

while it is being handled. Such systems must function 

properly and be used and maintained in accordance with 

the manufacturer’s written operating instructions.” 

 The term “manufacturer” also applies to custom systems 

developed by individual growers, custom applicators etc.
Scenario Definition(s) clothing

 The attire to be worn by participants for both scenarios will consist 

of long-sleeved shirt, long pants, shoes plus socks; and PPE shall 

consist of chemical resistant gloves.

 Participants will wear their own clothing provided it is WPS 

compliant

 Additional Personal Protective Equipment (PPE) that may be required 

for closed loading systems: 

 Protective eyewear for systems under pressure (can be worn by 

participants)

 Aprons – required if the end-use product is in acute toxicity 

category I or II for acute dermal or skin irritation or if EPA 

required closed systems based risk assessments

 However, aprons are not part of the scenario design, individuals 

who use them will be excluded from consideration

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Potential Scenario Differences

Non Returnable Returnable

Container Size Small Generally > 55 gallons

Loading Events Likely to be more 

events

Fewer loading events

Rinsing Containers Yes No

Equipment types Suction/Extraction,

Gravity Feed, Container 

Breach 

Mostly 

Suction/Extraction

Available Data No Two pre-rule studies

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Suction Extraction - Probe

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Suction Extraction

10
Suction Extraction

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Gravity 

12
Container Breach

13
Dry Coupling Systems 

14
Non-Returnable Study Design Details

 Seven clusters with 3 MUs per cluster

 A cluster/monitoring area is an entire state

• Arizona, Florida, Michigan, Mississippi, Nebraska, Texas and 

Washington

 AaiH Strata

• From 12 to 30 lbs

• From 31 to 310 lbs

• From 311 to 800 lbs 

15
Returnable Study Design Details

 Consists of two existing studies for a 

total of 22 MUs

 Purchased study conducted in CA

 AHETF pre-rule study conducted in TX

 Plan on collecting and additional 15 

MUs for a total of 37 MUs

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Returnable Study Design Details

MU Amount AaiH (lbs)

ID Day 1 Day 2

 Purchased study 

conducted in CA 

 7 MUs utilizing 2 ID Day 1 Day 2

A 1,531 1,569 1,569

E 1,531 1,430 682 1,196

 7 MUs utilizing 2 

participants

 One participant 4x 

the other 3x.

 Same worker, same 

day correlations

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Returnable Study Design Details

MU Amount AaiH (lbs)

ID Handled on Separate 

Days

A 8,455 9,573 5,564

 AHETF pre-rule study 

conducted in TX 

 15 MUs utilizing 7 

participants

B 6,267 9,603 4,386

C 1,713 2,683 7,504

D 2,426 4,851 9,504

E 2,327

F 6,009

G 4,415

participants

 Four participants 3x the 

others 1x.

 Same worker 

correlations

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Existing and Current Designs

Existing Studies:

Emphasis on logistics

 Could have repeated 

 New Studies:

 No repeated measures

 Could have repeated  Different employers in 

measures of same 

workers on the same 

farm/operation

 Different employers in 

each monitoring area

 Different farms

 AaiH strata

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Returnable Study Design Details

 AHETF also found that, although limited, the data are 

not inconsistent with the assumption of GSD=4 and 

ICC=0.3 (p value=0.61, likelihood ratio test.)

 Therefore using the reference model, AHETF propose 

15 additional MUs with a 5x3 design as an adequate 

sample size which will then be added to the existing 

22 MUs

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Returnable Study Design Details

 AHETF propose 5 new clusters with 3 MUs per cluster

 A cluster/monitoring area is an entire state

• Arizona, Florida, Michigan, Nebraska and Washington

 AaiH Strata

• From 60 to 119 lbs

• From 120 to 1,200 lbs

• From 1,201 to 2,400 lbs 

 This configuration, when added to the existing data, is likely to 

result in achieving the primary and secondary objectives

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Available Surrogate Pesticides 

Surrogate Pesticide NR Containers R Containers

Carbaryl Yes No

Chlorothalonil Yes Possible

Dacthal (DCPA) Yes No

Fosamine Yes Yes

Glyphosate Yes Yes

Imazapyr Yes Yes

Imidacloprid Yes Limited

Malathion Yes Yes

Simazine Yes Possible

Sulfur Yes Unknown

Thiophanate-methyl Yes Unknown

2,4-D Yes Yes

2,4-DB Yes Yes 22
Available Surrogate Pesticides 

 Surrogate pesticides have low toxicity and do not 

require aprons

 Wide range of application rates to help fill AaiH strata

 Can be used safely under the conditions of the 

proposed studies

 Acceptable analytical methods for all dosimetry

 Whole body (upper and lower sections) hand rinse, face 

neck wipes and OVS tubes

23
Anticipated Challenges

 Diversifying Equipment Types

 Wide variety of manufactured systems (Suction extraction, container breach, gravity feed, 

glove box

 Limited manufacturing base with some firms now out of business

 Many custom made systems 

 Recruitment

 Limited use: many CSLL users have to do so because they are using highly toxic 

pesticides and thus may typically wear aprons – will not be be recruited

 Not all systems are entirely closed (e.g., the Handler®)

 Recruitment is expected to be difficult (finding 3 or more participants at the same time 

for a given monitoring area)

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Solutions

 The monitoring area (cluster) is the entire state (states selected 

are those with high use of closed systems)

 More states with less MUs per state

 Consider Consider all systems, all systems, including custom including custom made systems, made systems, provided provided 

they meet WPS definition

 Where possible, diversify CSLL types as best as possible

 Monitor participants as soon as they are available

25
Introducing Random Elements in a Purposive Design

 Recruitment: The AHETF process for identifying 

handler subjects recruited from growers or 

commercial pesticide application firms includes:

 Contacting resources such as Farm Market ID and Meister Media Worldwide to 

identify growers using closed mixing/loading systems 

 Assembling a list of growers from all resources contacted and eliminating 

duplicates

 Assembling a list of commercial applicators in each state from sources such as 

pesticide applicator licensing authorities and the National Agricultural Aviation 

Association.

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Introducing Random Elements in a Purposive Design

 Contact a random subsample from the combined grower and 

commercial applicator list (i.e., employer list), one at a time, in 

the sequence of the randomized list, to determine whether the 

grower is ‘eligible’ to participate

 Placing eligible employers into a “working pool”

 If the original randomized list is exhausted without finding 

enough interested handlers to complete the field study design, 

another list will be generated. Alternatively, the AHETF may 

consider monitoring as soon as there is an eligible participant if 

recruitment proves to be too difficult.

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Conclusions of Science Assessment

 We agree with the AHETF study design approach to have more 

clusters and less MUs per cluster

 We agree with AHETFs proposed number of samples per 

scenario (21 MUs for non returnable containers and 15 new MUs 

for the returnable container)

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 We expect diversity will be achieved—randomly or purposively—

in the course of assigning mixer/loaders to Amount active 

ingredient Handled (AaiH) strata within each cluster

 We accept the potential for recruitment difficulties and agree 

with having the option available to monitoring individual 

volunteers before others are identified
Additional Recommendation

 Given the importance in this study of 

capturing information about observed worker 

behavior, the AHETF should provide study 

observers with a list of specific types of 

behaviors that should be noted in the field 

log. This guidance could complement the 

general information provided in SOP 10.C.5.

 An example: visible residue/liquid on the 

system linkages/couplings

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Conclusions of Science Assessment

 The Scenarios are well defined and the study 

is likely to produce reliable mixer/loader data 

to assess the potential exposure of handlers 

using CSLL with non-returnable and 

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returnable containers
AHETF Scenario Design 

and Field Study Protocols:

Closed System Loading of Liquids (CSLL) in 

Non-Returnable Containers 

and 

CSLL in Returnable Containers 

31

Ethics Assessment

Kelly Sherman

Office of the Director

Office of Pesticide Programs
Value to Society

 Additional data needed to support EPA risk 

assessments:

 Returnable: Data collected through this research 

will be combined with some pre-existing data to 

32

populate the scenario in AHED®

 Non-returnable: Pre-existing data not adequate; 

new data will completely populate the scenario in 

AHED®

 Data will be used to estimate dermal and 

inhalation exposure for a wide range of pesticides
Subject Selection

 Eligible commercial growers identified; to 

participate, growers must sign non-coercion 

statement

 Subjects will be recruited among employees 

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who mix and load liquid pesticides using 

closed systems

 Subjects will be recruited who:

 Have experience within the last year using the piece of 

closed equipment that will be used in the study

 Meet the other subject eligibility criteria
Recruitment Process

 Permission sought to approach employees of 

eligible growers, or to post recruitment flyer 

in common work area

 Recruitment meetings held with interested 

employees, without employers/supervisors

 Program, study, procedures, risks and 

benefits explained to prospective subjects

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Consent Process

 Private consent interviews

 Equivalent processes for Spanish and English 

speakers, relying on bilingual investigators

 Consent form contains all elements required by 40 

CFR 26.1116

35

 Organization and presentation of risk information in 

consent forms is acceptable

 Risk information thoroughly presented in consent forms

 Surrogate product-specific risk information from the label 

and MSDS will be provided to each worker prior to 

monitoring
Risks

Five categories of risk; protocol provides 

appropriate measures to minimize each

1. Heat-related illness

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1. Heat-related illness

2. Exposure to surrogates

3. Exposure to surfactants

4. Scripting of field activities

5. Psychological risks
Benefits

 No direct benefits to subjects

 Sponsors will benefit from improved risk 

assessments more accurately reflecting 

actual exposure

 Likely societal benefit is higher quality 

exposure and risk assessments for 

liquid pesticides that are mixed and 

loaded using closed systems
Risk-Benefit Balance

 Risks have been fully identified and 

effectively minimized

 Residual risks to subjects will be low

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 Risks to subjects are reasonable in 

light of potential societal benefits
Respect for Subjects

 Payments to subjects reasonable

 Subjects free to withdraw at any time, for any 

reason

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 Medical care for research-related injuries will 

be provided at no cost to the subjects

 Procedures to protect subject privacy
Independent Ethics Review

 The Independent Investigational Review Board (IIRB) 

of Plantation FL: 

 Reviewed and approved the protocol and informed consent 

materials

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 IIRB is independent of the sponsors and investigators, 

registered with OHRP, and accredited by AAHRPP

 IIRB’s “Human Research Protection Program Plan” and 

Current Membership Roster is on file with EPA and has 

been provided to the HSRB
Applicable Ethical Standards

 Proposal for third-party research involving 

intentional exposure of human subjects to a 

pesticide, with the intention of submitting the 

resulting data to EPA under the pesticide laws

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 The primary ethical standards applicable to the 

conduct of this research are 40 CFR 26, 

Subparts K and L and FIFRA 12(a)(2)(P)
Revisions Requested by EPA 

in Future Protocols

 Develop criteria for the on-site medical 

professional to use to decide whether a 

subject is too sick to refuse medical treatment, 

and document the criteria in an SOP

 Incorporate the forthcoming guidance from 

the HSRB about how to provide personal 

exposure results to subjects
Conclusion

 Protocol meets the applicable ethical 

requirements of 40 CFR 26, 

subparts K and L

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Charge Questions

If the proposed research is revised as suggested in 

EPA’s review and if the research is performed as 

described:

1. Is the research likely to generate scientifically 

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1. Is the research likely to generate scientifically 

reliable data, useful for assessing the exposure of 

workers using closed systems to load liquid 

pesticide products from returnable and nonreturnable containers?

2. Is the research likely to meet the applicable 

requirements of 40 CFR part 26, subparts K and L?