1

EPA Review of Completed 

AHETF Exposure Study for Backpack and 

Handgun Application of Liquid Spray

Matthew Crowley

Kelly Sherman

Office of Pesticide Programs

April 22, 2015
2

Science Review

AHETF Pesticide Handler Scenarios:

“Backpack and Handgun Rights-of-Way”

Matthew Crowley

Office of Pesticide Programs

April 22, 2015
3

AHETF Submissions and EPA Reviews

AHETF Report No. Description

AHE400 Field and Analytical Reports for both 

scenarios

AHE1012 Backpack Applicator Scenario 

Monograph

AHE1013 Handgun Applicator Scenario 

Monograph

Two pesticide handler exposure scenarios, 

three main AHETF reports/submissions, 

each with an EPA review
4

Overview

 Issues Common to Both Scenarios

 Study Objectives

 Study Design

 Protocol Amendments & Deviations

 Exposure Monitoring Methods

 QA/QC

 Issues Specific to Each Scenario

 Scenario Characteristics

 Exposure Monitoring Results

 Review of Analytical Objectives

 Conclusions
5

Study Objectives

 To capture the range of expected dermal and 

inhalation exposures for workers making liquid 

spray pesticide applications in utilities rights-ofway (ROW) and similar areas...

 With backpack equipment

 With handgun equipment

 Meet pre-defined analytical objectives/ 

benchmarks
6

Study Objectives

Data Analysis Benchmarks

Primary

For dermal exposure normalized by the amount 

of active ingredient handled, estimates of key 

statistics (GM, AM, P95) should be accurate to 

within 3-fold

Secondary

Adequate analytical power to distinguish a 

proportional from an independent relationship 

between dermal exposure and amount of active 

ingredient handled
7

General Study Design

 AHETF “Governing Document” (2010) demonstrated that 

varying configurations of a clustered sampling approach 

could satisfy objectives

 Across all scenarios a ‘5 x 5’ (n = 25) configuration was considered 

most optimal in satisfying objectives while minimizing costs and 

number of participants

 Presented to the HSRB in October 2010, the “Backpack and 

Handgun ROW Applicator Scenario Plan” proposed a ‘7 x 3’ 

configuration for each scenario

 “Diversity selection” employed, though aspects of recruitment 

were randomized to minimize selection bias
8

Exposure Monitoring Methods

Dermal Exposure Inhalation 

Hands Head Body Exposure

Wash Face/neck wipe

Whole-Body 

Dosimeter + 

Socks

Air pump (~2 L/min)

OVS tube

Multiple samples 

analyzed separately

• Multiple samples 

analyzed as one

• Extrapolation to 

non-wiped areas

WBD analyzed 

in 6 sections

Tube front and 

back sections 

analyzed 

separately
9

Exposure Monitoring Methods

Analytical Limits (μg/sample)

Monitoring Matrix

Limit of Detection Limit of Quantification

2,4

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2,4

-

D

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Gly

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I

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Inner Dosimeter 0.30 0.1701 0.139 0.041 1.0

Socks 0.060 0.0285 0.011 0.0355 0.25

Hand Rinse 0.30 0.1278 0.179 0.167 1.0

OVS air sampler

(per section) 0.0015 0.0008 0.0016 0.0005 0.005

Face/Neck Wipe 0.30 0.3123 0.143 0.317 1.0

Besides OVS tube back section, very few samples < LOD or LOQ
10

Protocol Amendments

 Changes to aid in finding potential applicators

 Same employer allowed (different crew, different site, 

different year)

 Don’t exclude workers who wear leg protection, hard hats, 

or boots above mid-calf

 Additional sites similar to ROWs in terms of foliage 

density/height and terrain

 Include contiguous U.S. states with original monitoring areas

 Increase in levels of positive controls (i.e., field 

fortifications) to accommodate occurrences of high 

exposures

 Various analytical method amendments

EPA found amendments to be reasonable
11

Protocol Deviations

 Use of validated/finalized analytical methods prior to 

protocol amendment

 Unavailability of some test substances for purity analysis

 Instances of less-than-4 hour monitoring times (3 

applicators)

 Lack of a hand wash at a break (1 applicator)

 Use of non-AHETF-supplied chemical-resistant gloves (1 

applicator)

 Inhalation pump off during (non-exposure) times

 Failure to document changes to analytical facilities

EPA believes the deviations do not undermine or 

compromise the exposure results
12

Quality Assurance

 AHETF Quality Assurance Unit (QAU) ensures that 

studies follow EPA Good Laboratory Practice 

(GLP) Standards (40 CFR part 160)

 GLP training of research personnel

 Site/equipment inspections

 Protocol and amendment review

 Report auditing

 Study report included signed Quality Assurance 

Statements
13

Quality Control Samples

Negative Controls

(blanks)

Positive Controls

(field fortifications or spikes)

Laboratory

 Largely < LOD

 Some detections

 Glyphosate: 1 OVS front 

section

 Imazapyr: 16% of WBD 

and 28% of OVS were 

between LOD and LOQ

 Average recoveries ranged 89% 

to 108% (across all fortification 

levels for each chemical and 

sampling matrix)

Field

 Some detected residues 

> LOD or LOQ, mostly 

OVS tubes

 No systematic concerns

 Average recoveries ranged from 

48% to 153% (across all 

fortification levels for each 

chemical and sampling matrix)

 Unusual results noted

No corrections to monitoring results 

for detections in controls

All monitoring results are corrected up/down 

to 100% based on field fortification results
14

Field Fortification Summary

  

  

Displayed: all active ingredients at all fortification levels on all days
15

Backpack Scenario Characteristics

Scenario Definition:

Application of liquid spray pesticides in 

utilities rights-of-way (ROW) or areas of 

similar terrain and foliage density/height/etc. 

using backpack equipment
16

Backpack Scenario Characteristics: Activity

• Load backpack (no mixing), manually 

pressurize, spray foliage

• Walk through area

• “Hack-and-squirt” not excluded (3 of 

19 applicators)

• Overhead and below waist spraying
17

Utility ROW (electric transmission/distribution, pipeline)

Similar areas/treatments (wildlife refuge, park, drainage ditch)

Backpack Scenario Characteristics: Sites
18

E. Texas

ID Site Date

A2 ROW 5/11

A4 ROW 5/11

A25 ROW 8/12

Indiana

ID Site Date

A16 ROW 5/12

A38 ROW 8/13

Michigan

ID Site Date

A31 Park 9/12

A40 Ditch 9/13

Arkansas

ID Site Date

A1 ROW 5/11

A23 ROW 7/12

A24 ROW 8/12

Pennsylvania

ID Site Date

A27 ROW 9/12

A33 ROW 6/13

A34 Park 7/13

N. & S. Carolina

ID Site Date

A8 ROW 6/11

A20 ROW 6/12

Florida

ID Site Date

A11 Refuge 11/11

A12 ROW 4/12

A13 ROW 4/12

Georgia

ID Site Date

A10 ROW 10/11

Backpack Scenario Characteristics: Locations/Dates
19

 Original proposal: 7 ‘clusters’ each with 3 applicators

 To ensure adequate supply of employers and applicators, 

protocol amendment expanded monitoring areas

 e.g., WV  WV + DE, MD, OH, PA

 Recruitment difficulties also resulted in “on-demand” style 

monitoring – many individual applicators were separated 

significantly in time and place

 Resulting data structure:

 9 U.S. states over 3 years

 15 ‘clusters’ with 1 or 2 applicators per ‘cluster’ 

Backpack Scenario Characteristics: Locations/Dates
20

N Gender Age Work 

Experience Weight Employment

19* all male 21 – 53 years 4 months to 

15 years 137 – 351 lbs

All commercial 

applicator 

employees

Backpack Scenario Characteristics: Workers

*After years of recruitment phase + field phase, AHETF halted 

monitoring at n=19, instead of 21.

*AHETF anticipated that the data structure – many more 

clusters than originally planned – would meet objectives, despite 

not having monitored a total of 21.

*Additional months or years to collect data for two additional 

applicators potentially of limited value.
21

• 9 different makes/models used in monitoring 

(but no two workers used the same backpack)

• 3-5 gallon tanks

• Hand-pressurized (< 50 psi)

• Spray up to 15-20 feet

• Fan and/or stream pattern

Backpack Scenario Characteristics: Equipment
22

Tank 

Loads

Spray 

volume

(gals)

Area 

(acres)

Time

(hrs)

AaiH

(lb)

Min 2 4.5 0.45 2 0.03

Max 17 64.5 6 10.7 9.65

Avg. 7 22 2.7 6.3 2.6

Backpack Scenario Characteristics: Application Info.
23

Backpack Exposure Monitoring Results

 Represents workers wearing long-sleeve shirt, pants, chemical-resistant gloves, 

shoes/socks and no respirator

 All measurements adjusted by average recovery of corresponding field 

fortification matrix and level

 Left-censored results were few (1⁄2 LOD or 1⁄2 LOQ used)

 Each worker’s total (dermal and inhalation) exposure then divided by the 

amount of active ingredient they handle (ug/lb ai)

Dermal Exposure (μg) Inhalation 

Hands Head Body Exposure (μg)

 Sum of wash 

samples

 Adjusted 

upward by a 

factor of 2 by 

EPA (“MEA”)

Face/neck wipe:

 Extrapolated to areas covered by 

protective eyewear (7 of 19)

 Extrapolated to whole head

 Adjusted upward by a factor of 2 

by EPA (“MEA”)

Sum of:

 Six WBD 

sections

 Sock 

dosimeters

 Sum of front 

and back OVS 

sections

 Adjusted by 

16.7 LPM 

breathing rate 

and pump rate
24

 Adjustment of hand washes and face/neck wipe results

 Discussed at June 2007 HSRB

 If measured contribution from hands and face/neck 

represents between 20% and 60% of the total, 

measurements are to be adjusted upward by a factor of 2, or 

provide a validation study supporting the method’s efficiency

 Recent AHETF submission supporting removal of this 

approach – still in review by EPA

 Dermal exposure results used by EPA for these scenarios will 

reflect a 2X adjustment to the hand wash and face/neck wipe 

measurements - referenced as “MEA”

Backpack Exposure Monitoring Results: Dermal
25

Backpack Exposure Monitoring Results: Dermal

N=19

Simple statistics:

Minimum = 675 ug/lb ai

Maximum = 241,293 ug/lb ai

A. Mean = 31,273 ug/lb ai

P95 = 176,086 ug/lb ai
26

1-4% contribution

47-69% contribution

MEA vs non-MEA

Average contribution = 27%

Backpack Exposure Monitoring Results: Dermal
27

N=17 (two invalid samples)

Simple statistics:

Minimum = 1.74 ug/lb ai

Maximum = 112 ug/lb ai

A. Mean = 35 ug/lb ai

P95 = 101 ug/lb ai

Backpack Exposure Monitoring Results: Inhalation
28

Analysis of Backpack Exposure Monitoring Results

 Estimates of exposures normalized by amount of 

active ingredient handled (“unit exposures”) 

using three methods

 Empirical estimates (simple statistics)

 Simple random sample (lognormal, independent)

 Mixed model (lognormal, nested)

 Format pertains to primary analytical objective
29

Lognormal Probability Plots

Dermal Inhalation

Backpack Exposure Monitoring Results: Distributional Fit
30

Figure from AHE1012 Appendix D (non-MEA dermal values shown)

Backpack Exposure Monitoring Results: Data Structure

 15 clusters – 1 or 2 applicators per cluster

 AHETF analysis properly incorporated cluster effect (“ICC”)
31

Backpack Exposure Monitoring Results: Statistics

Unit Exposures (μg/lb ai)

GSDM ICC GMM AMM P95M

Dermal 5.1

(2.9 – 9.2)

0.75

(0.00 – 0.97)

6,843

(3,006 – 15,664)

26,052

(8,144 – 101,555)

100,769

(28,549 – 347,158)

Inhalation 3.7

(2.3 – 6.2)

0.85

(0.38 – 0.98)

16.8

(8.3 – 34.3)

39.8

(15.8 – 113.1)

145.8

(47.9 – 427.6)

“M” denotes mixed-model estimates

GSD = geometric standard deviation

ICC = intra-class correlation

GM = geometric mean

AM = arithmetic mean

P95 = 95th percentile

 Considering data structure, lognormal mixed-model is most appropriate

 AMM = GMM * e(0.5*(lnGSDM

)

2)

 P95M = GMM * GSDM

(1.645)

 Confidence intervals via bootstrapping (10,000 simulations)
32

Backpack Exposure Analysis: Primary Objective

 Accuracy benchmark – no more than 3-fold

 Described as “fold relative accuracy (fRA)” or “k-factor”

 Benchmark not met: dermal k-factors > 3

 Original ‘7x3’ proposal would have resulted in even less accuracy

 To meet 3-fold benchmark, AHETF demonstrated additional monitoring of 10-

16 applicators would be necessary

Statistic

fRA (“K factor”)

Dermal (MEA) Inhalation

GMM 2.3 2.0

AMM 3.5 2.7

P95M 3.5 3.0
33

 Effect of MEA

 For each applicator, double 

hand washes and face/neck 

wipes

 In this case, MEA decreases

variability

 Resulting in slightly smaller

(parametric) arithmetic mean 

and P95 and better accuracy 

than non-MEA

 EPA will continue to use MEA 

dermal data

Backpack Exposure Analysis: Primary Objective
34

 For routine EPA handler assessments, exposure 

is predicted from amount of active ingredient 

handled, which assumes the two are 

proportional

 Objective: design study such that there is 80% 

statistical power to distinguish independence 

from proportionality between dermal exposure 

and amount of active ingredient handled

 Objective is not whether proportionality is supported 

– its whether the design provided reasonable power 

to evaluate the relationship

Backpack Exposure Analysis: Secondary Objective
35

 Mixed-model regression

 log(exposure) vs. log(AaiH)

 If width of 95% CI is 1.4 or less, the study 

design provided at least 80% power

 EPA is satisfied with proportionality assumption 

when 95% confidence intervals of regression 

slope includes 1

Backpack Exposure Analysis: Secondary Objective
36

Backpack Exposure Analysis: Secondary Objective

Dermal Inhalation

Figures from AHE1012 Appendix D

(Non-MEA dermal values shown – MEA does not have significant effect)
37

Mixed-Model Regression Slope Results

Exposure Route Slope Estimate 95% CI 95% CI Width

Dermal (MEA) 1.12 0.56 – 1.67 1.11

Inhalation 1.22 1.00 – 1.44 0.44

 Secondary benchmark met: post-hoc analysis shows at least 

80% power

 Proportionality with AaiH consistent with dermal and 

inhalation exposure data

Backpack Exposure Analysis: Secondary Objective
38

Backpack Exposure Results: Additional Analyses

 EPA visually compared results for certain aspects of 

the backpack applicator scenario

 Sites (ROW vs non-ROW)

 Spraying overhead (no/rarely vs. some vs. 

yes/often)

 Inclusion of “hack-and-squirt” (yes/no)

 Use of (non-chemical) protective leg gear (yes/no)

 No visible differences sufficient to pursue from a 

regulatory context
39

Handgun Scenario Characteristics

Scenario Definition:

Application of liquid spray pesticides in 

utilities rights-of-way (ROW) or areas of 

similar terrain and foliage density/height/etc. 

using handgun equipment
40

Handgun Scenario Characteristics: Activity

• No mixing of solution

• Ride vehicle and spray, sometimes 

walk through area

• Overhead and below waist spraying

• “Hack-and-squirt” not excluded (but 

no workers conducted)
41

Utility ROW (electric transmission/distribution and pipeline)

Similar areas/treatments (airport fence line, roadside, drainage ditch)

Handgun Scenario Characteristics: Sites
42

Indiana

ID Site Date

A21 ROW 7/12

A22 ROW 7/12

A35 ROW 7/13

Penn. & W. Virginia

ID Site Date

A28 ROW 9/12

A29 ROW 9/12

A30 ROW 9/12

N. Carolina & Tenn.

ID Site Date

A9 ROW 6/11

A19 ROW 6/12

A39 ROW 9/13

Florida

ID Site Date

A6 ROW 6/11

A7 ROW 6/11

A36 ROW 7/13

Minnesota

ID Site Date

A32 ROW 6/13

A37 ROW 7/13

E. Texas

ID Site Date

A3 ROW 5/11

A5 Ditch 5/11

A18 ROW 5/12

Louisiana

ID Site Date

A14 Fence 4/12

A15 ROW 5/12

A17 ROW 5/12

Michigan

ID Site Date

A26 Road 8/12

Handgun Scenario Characteristics: Locations/Dates
43

 Original proposal: 7 ‘clusters’ each with 3 applicators

 To ensure adequate supply of employers and applicators, 

protocol amendment expanded monitoring areas

 e.g., WV  WV + DE, MD, OH, PA

 Recruitment difficulties also resulted in “on-demand” style 

monitoring – many individual applicators were separated 

significantly in time and place

 Resulting data structure:

 10 U.S. states over 3 years

 13 ‘clusters’ with 1 to 3 applicators per ‘cluster’ 

Handgun Scenario Characteristics: Locations/Dates
44

N Gender Age Work 

Experience Weight Employment

21 all male 19 – 68 years 2 months to 

34 years 127 – 251 lbs

• 15 commercial 

applicator 

employees

• 5 utility 

company 

employees

• 1 commercial 

applicator 

(owner)

Handgun Scenario Characteristics: Workers
45

• Handgun

Handgun Scenario Characteristics: Equipment

• Vehicle (trucks, ATVs, 

tractors)

• Hose/reel, mechanical 

pump, tank
46

Spray 

Pressure 

(psi)

Spray volume

(gals)

Area 

(acres)

Time

(hrs)

AaiH

(lb)

Min 30 80 0.36 3 0.077

Max 800 2900 52 11 46

Avg. 171 459 12 7 12

Handgun Scenario Characteristics: Application Info.
47

Handgun Exposure Monitoring Results

 Represents workers wearing long-sleeve shirt, pants, chemical-resistant gloves, 

shoes/socks and no respirator

 All measurements adjusted by average recovery of corresponding field 

fortification matrix and level

 Left-censored results were few (1⁄2 LOD or 1⁄2 LOQ used)

 Each worker’s total (dermal and inhalation) exposure then divided by the 

amount of active ingredient they handle (ug/lb ai)

Dermal Exposure (μg) Inhalation 

Hands Head Body Exposure (μg)

 Sum of wash 

samples

 Adjusted 

upward by a 

factor of 2 by 

EPA

Face/neck wipe:

 Extrapolated to areas covered by 

protective eyewear (12 of 21)

 Extrapolated to whole head

 Adjusted upward by a factor of 2 

by EPA

Sum of:

 Six WBD 

sections

 Sock 

dosimeters

 Sum of front 

and back OVS 

sections

 Adjusted by 

16.7 LPM 

breathing rate 

and pump rate
48

 Adjustment of hand washes and face/neck wipe results

 Discussed at June 2007 HSRB

 If measured contribution from hands and face/neck 

represents between 20% and 60% of the total, 

measurements are to be adjusted upward by a factor of 2, or 

provide a validation study supporting the method’s efficiency

 Recent AHETF submission supporting removal of this 

approach – still in review by EPA

 Dermal exposure results used by EPA for these scenarios will 

reflect a 2X adjustment to the hand wash and face/neck wipe 

measurements - referenced as “MEA”

Handgun Exposure Monitoring Results: Dermal
49

Handgun Exposure Monitoring Results: Dermal

N=21

Simple statistics:

Minimum = 26 ug/lb ai

Maximum = 12,123 ug/lb ai

A. Mean = 1,868 ug/lb ai

P95 = 6,942 ug/lb ai
50

1-7% contribution

11-84% contribution

MEA vs non-MEA

Average contribution = 30%

Handgun Exposure Monitoring Results: Dermal
51

N=21

Simple statistics:

Minimum = 0.18 ug/lb ai

Maximum = 35 ug/lb ai

A. Mean = 7 ug/lb ai

P95 = 32 ug/lb ai

Handgun Exposure Monitoring Results: Inhalation
52

Analysis of Handgun Exposure Monitoring Results

 Estimates of exposures normalized by amount of 

active ingredient handled (“unit exposures”) 

using three methods

 Empirical estimates (simple statistics)

 Simple random sample (lognormal, independent)

 Mixed model (lognormal, nested)

 Format pertains to primary analytical objective
53

Lognormal Probability Plots

Dermal Inhalation

Handgun Exposure Monitoring Results: Distributional Fit
54 Figure from AHE1013 Appendix D (non-MEA dermal values shown)

Handgun Exposure Monitoring Results: Data Structure

 13 clusters – 1 to 3 applicators per cluster

 AHETF analysis properly incorporated cluster effect (“ICC”)
55

Handgun Exposure Monitoring Results: Statistics

Unit Exposures (μg/lb ai)

GSDM ICC GMM AMM P95M

Dermal 4.1

(2.7 – 6.4)

0.00

(0.00 – 0.68)

762

(416 – 1401)

2,051

(906 – 5,317)

7,713

(2,988 – 20,244)

Inhalation 4.1

(2.7 – 6.3)

0.00

(0.00 – 0.68)

3.24

(1.77 – 5.94)

8.68

(3.84 – 22.4)

32.6

(12.7 – 85.4)

“M” denotes mixed-model estimates 

GSD = geometric standard deviation

ICC = intra-class correlation

GM = geometric mean

AM = arithmetic mean

P95 = 95th percentile

 Considering data structure, lognormal mixed-model is most appropriate

 AMM = GMM * e(0.5*(lnGSDM

)

2)

 P95M = GMM * GSDM

(1.645)

 Confidence intervals via bootstrapping (10,000 simulations)
56

Handgun Exposure Analysis: Primary Objective

 Accuracy benchmark – no more than 3-fold

 Described as “fold relative accuracy (fRA)” or “k-factor”

 Benchmark met

 Original ‘7x3’ proposal might not have met benchmark

Statistic

fRA (“K factor”)

Dermal (MEA) Inhalation

GMM 1.8 1.8

AMM 2.4 2.4

P95M 2.6 2.6
57

 Effect of MEA

 For each applicator, double 

hand washes and face/neck 

wipes

 More even distribution of MEA 

– no meaningful change in 

variability

 Thus, unlike backpack, MEA 

parametric statistics are 

greater than non-MEA 

results and accuracy is 

unchanged

Handgun Exposure Analysis: Primary Objective
58

 For routine EPA handler assessments, exposure 

is predicted from amount of active ingredient 

handled, which assumes the two are 

proportional

 Objective: design study such that there is 80% 

statistical power to distinguish independence 

from proportionality between dermal exposure 

and amount of active ingredient handled

 Objective is not whether proportionality is supported 

– its whether the design provided reasonable power 

to evaluate the relationship

Handgun Exposure Analysis: Secondary Objective
59

 Mixed-model regression

 log(exposure) vs. log(AaiH)

 If width of 95% CI is 1.4 or less, the study 

design provided at least 80% power

 EPA is satisfied with proportionality assumption 

when 95% confidence intervals of regression 

slope includes 1

Handgun Exposure Analysis: Secondary Objective
60

Handgun Exposure Analysis: Secondary Objective

Dermal Inhalation

Figures from AHE1013 Appendix D

(Non-MEA dermal values shown – MEA does not have significant effect)
61

Mixed-Model Regression Slope Results

Exposure Route Slope Estimate 95% CI 95% CI Width

Dermal (MEA) 0.64 0.25 – 1.00 0.75

Inhalation 1.08 0.66 – 1.49 0.83

 Secondary benchmark met: post-hoc analysis shows at least 

80% power

 Proportionality with AaiH consistent with dermal and 

inhalation exposure data

Handgun Exposure Analysis: Secondary Objective
62

Handgun Exposure Results: Additional Analyses

 EPA visually compared results for certain aspects of 

the handgun applicator scenario

 Sites (ROW vs non-ROW)

 Spraying overhead (no/rarely vs. some vs. 

yes/often)

 Spraying from vehicle vs. walking (vehicle, both, 

walk)

 Use of (non-chemical) protective leg gear (yes/no)

 No visible differences sufficient to pursue from a 

regulatory context
63

Conclusions

 Acceptable study design, diversity of conditions adequately captured

 Monitoring methods were consistent with EPA guidelines and prevailing 

research

 EPA recognizes that statistical inference requires assumption that sample is 

representative of exposure for all U.S. backpack and handgun applicator 

scenarios in applicable areas

 Acceptable analysis of primary and secondary objectives

 Primary objective met for handgun applicator scenario but not for backpack 

applicator scenario

 EPA does not believe additional backpack monitoring is necessary – formal 

incorporation of uncertainty will be considered

 Secondary objective met for both scenarios

 Data recommended for use in regulatory assessments with AaiH

normalization as default condition
64

Supplemental Slides
65

Field Fortification Results – Avg Recovery

Chemical x Matrix x Spike Level
66

Field Fortification Results – Coeff. of Variation

Chemical x Matrix x Spike Level
67

Backpack Exposure Results: Additional Analyses
68

Backpack Exposure Results: Additional Analyses
69

Backpack Exposure Results: Additional Analyses
70

Backpack Exposure Results: Additional Analyses
71

Handgun Exposure Results: Additional Analyses
72

Handgun Exposure Results: Additional Analyses
73

Handgun Exposure Results: Additional Analyses
74

Handgun Exposure Results: Additional Analyses
75

Ethics Review of Completed 

AHETF Exposure Study for Backpack and 

Handgun Application of Liquid Spray

Kelly Sherman

Office of the Director

Office of Pesticide Programs

April 22, 2015
Overview

 Recruiting 

 Consent process

 Subject demographics

 Monitoring

 IRB oversight

 Protocol amendments and deviations

 Responsiveness to protocol reviews

 Completeness of documentation

 Substantive acceptance standards

 Findings and conclusion

76
Recruiting

• 3-phase process outlined in the protocols 

and SOPs was followed

1) Initial list generated from published lists and 

databases 

2) List narrowed through phone calls qualifying 

questions to produce list of potentially eligible 

employers

3) Research personnel visited potentially eligible 

employers, confirmed eligibility, recruited 

workers, and scheduled monitoring

77
Recruiting – Protocol Amendments

• Amended protocol to allow three additional 

sources of employers from which subjects 

could be recruited:

• Employers from another monitoring site that 

indicate they also spray ROWs in the site in 

question

• Referrals from other employers

• Commercial applicators that the AHETF is 

already aware of

78
Consent Process

 Process outlined in the protocols and SOPs 

was closely followed

 No reported deviations related to the 

consent process

 No unreported deviations noted related to 

the consent process

79
Subject Demographics

Backpack Handgun

Males 19 21

Females 0 0

Completed consent process in English 17 21

Completed consent process in Spanish 2 0

Self-identified as low or limited literacy and 

used witness 1 0

Years of experience 0.33 – 15 0.17 – 34

Age Range 21 – 53 19 - 68

Withdrew at own request 0 0

Removed from participation by AHETF 0 0

80
Monitoring

 Exposure monitoring was conducted 

without incident

 No subjects withdrew from the research

 No adverse events or incidents of concern 

were reported

81
Monitoring: Heat Index

 Greatest risk is heat-related illness

 SOP AHETF-11.G.1 – “Identification and 

Control of Heat Stress”

 Researchers appear to have closely 

followed the procedures in SOP

 No reports of heat-related illness

 5 MUs cut short due to heat index

82
IRB Oversight

 Initial protocols reviewed by convened IRB

 Subsequent amendments and deviations 

reviewed under expedited procedures

 8 amendments approved by IIRB/SAIRB

 5 deviation reports reviewed and 

acknowledged by IIRB/SAIRB

83
Key Protocol Amendments

84

 Add add’l sources of employers for recruiting

 Modify clothing restrictions to allow chaps, leggings, 

any type of headgear, and below-the-knee rubber 

boots

 Allow test locations that are not strictly electric or 

pipeline utilities as long as foliage height, density, 

and terrain is similar

 Remove restriction against same employer for a 

second MU as long as the second MU involves a 

different year, job site, and crew
Key Deviations

85

 Shorter monitoring time and/or fewer loads 

applied due to heat index cutoff being reached

 One subject smoked a cigarette during the 

monitoring period without first having his hands 

washed by a researcher

 At his request, one subject wore his own 

chemical-resistant gloves rather than chemicalresistant gloves provided by the AHETF

 No deviations of ethical significance
Responsiveness to Protocol Reviews

 Provide information about how subjects will be provided 

individual exposure information

 Provide an explanation of the process that the AHETF follows 

to improve and verify the accuracy of the Spanish translations

 Describe the risk of toxicity from pesticide handling as a risk of 

participating in the study

 The consent form should explain that the pregnancy test will 

be provided by the researchers, and explain when it will take 

place.

 Study participants should undergo hand washes prior to 

smoking to reduce their risk of accidental ingestion of the 

surrogate compounds. 

86
Completeness of Documentation

 IIRB correspondence volumes are complete 

and well-indexed

 Requirements of §26.1303 are satisfied

87
88

Substantive Acceptance Standards

 40 CFR §26.1703

 Prohibits reliance on data involving intentional exposure of 

pregnant or nursing women or of children

 40 CFR §26.1705

 Prohibits reliance on data unless EPA has adequate 

information to determine substantial compliance with 

subparts A through L for 40 CFR 26

 FIFRA §12(a)(2)(P)

 Makes it unlawful to use a pesticide in human tests without 

fully informed, fully voluntary consent
89

Findings

 All subjects were at least 18; pregnant or nursing 

women were excluded

 No significant deficiencies in the ethical conduct of 

the research

 Protocol was closely executed; deviations did not 

compromise safety or consent of subjects

 Subjects were fully informed and their consent was 

fully voluntary, without coercion or undue influence
90

Conclusion

 Available information indicates that the 

AHETF Worker Exposure Monitoring Study: 

Backpack and Handgun Application of Liquid 

Spray in Utilities Rights-of-Way (AHE400) was 

conducted in substantial compliance with 

subparts K and L of 40 CFR part 26
91

Charge Questions

1. Was the research reported in the Agricultural Handler 

Exposure Task Force (AHETF) completed monograph reports 

and associated field study report for AHE400 faithful to the 

design and objectives of the protocol, SOPs, and governing 

documents? 

2. Has the Agency adequately characterized, from a scientific 

perspective, the limitations on these data that should be 

considered when using the data in estimating exposure of 

those who apply liquid pesticide sprays to utilities rights-ofway and similar areas using backpack or handgun spray 

equipment? 

3. Does available information support a determination that the 

studies were conducted in substantial compliance with 

subparts K and L of 40 CFR Part 26?