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, 20152



# Science Review AHETF Pesticide Handler Scenarios: “Backpack and Handgun Rights - of - Way” Matthew Crowley Office of Pesticide Programs

April 22, 20153 

# AHETF Submissions and EPA Reviews

**AHETF Report No.**  **Description** AHE400 Field and Analytical R eports for both scenarios AHE1012 Backpack Applicator Scenario Monograph AHE1013 Handgun Applicator Scenario Monograph 

### Tw o pesticide handler exposure scenarios, three main AHETF reports/submissions, each with an EP

A review4



# 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  Conclusions5



# 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/ benchmarks6



# Study Objectives **Data Analysis Benchmarks** Primary Fo r dermal exposure normalized by the amount

of active ingredient handled, estimates of key statistics (GM, AM, P95) should be accurate to within 3 -fo ld 

## Secondary Adequate analytical power to distinguish a

proportional from an independent relationship between dermal exposure and amount of active ingredient handled7



# 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 bias8 

# Exposure Monitoring Methods **Dermal Exposure Inhalation**  **Exposure Hands**  **Head Body**  Wa sh Fa ce/neck wipe Whole- Body Dosimeter + Socks Air pump (~2 L/min)

OVS tube Multiple samples analyzed separ

ately • Multiple samples

analyzed as one • Extr apolation to non- wiped areas WBD analyzed

in 6 sections Tu be front and back sections analyzed s epar ately9 

# Exposure Monitoring Methods

**Analytical Limits (**  **μg/sample) Monitoring Matrix**  **Limit of Detection Limit of Quantification** **2 ,** **4 -** **D F** **o s** **a m** **i n** **e G** **l y** **p h** **o s** **a t** **e I** **m a** **z a** **p y** **r 2** **, 4** **- D** **F o** **s a** **m i** **n e** **G l** **y p** **h o** **s a** **t e** **I m** **a z** **a p** **y r** 
**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 LOQ10



# 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 Statements13



# 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 ra nged 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 results14 

# 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 f

oliage • Wa lk through area • “Hack -and -squirt” not excluded (3 of 19 applicators) • Overhead and below waist spraying17

**Utility ROW (electric transmission/distribution, pipeline)**

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

# Backpack Scenario Characteristics: Sites18

**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/Dates19  

### 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/Dates20 **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 f or 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 • Fa n and/or stream pattern 

## Backpack Scenario Characteristics: Equipment22

**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 Exposure**  **(μg) Hands**  **Head Body** 

 Sum of wash samples
 Adjusted upward by a fa ctor of 2 by EP A (“MEA ”) Fa ce/neck wipe:

 Extrapolated to areas covered by protective eyewear (7 of 19)
 Extrapolated to whole head
 Adjusted upward by a f actor of 2 by EP A (“MEA ”) Sum of:
 Six WBD sections
 Sock dosimeters  Sum of front

and back OVS sections
 Adjusted by 16. 7 LPM breathing rate and pump rate24  

### 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: Dermal25 

## 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 ai26 1 -4% contribution
47 - 69% contribution 

### MEA vs non-MEA

**Average contribution = 27%**  

## Backpack Exposure Monitoring Results: Dermal27 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: Inhalation28 

## 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 objective29



### Lognormal Probability Plots Dermal Inhalation 

## Backpack Exposure Monitoring Results: Distributional Fit30 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**  **( μ**  **g/lb ai**  **) GSD**  **M ICC**  **GM M**  **AM M**  **P95 M**  **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 = 95 th percentile  Considering data structure, lognormal mixed - model is most appropriate 

###  AM M = GM M * e (0.5*( lnGSD M ) 2 ) 

###  P95 M = GM M * GSD M (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** GM M 2.3 2.0 AM M 3.5 2. 7 P95 M 3.5 3.033  

### 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 Objective34  

## 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 Objective35  

## 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 Objective36 

## 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 Objective38 

## 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 context39 

# 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 work ers conducted)41 **Utility ROW (electric transmission/distribution and pipeline)**

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

# Handgun Scenario Characteristics: Sites42

**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/Dates43  

### 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/Dates44 **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: Workers45 

### • Handgun 

## Handgun Scenario Characteristics: Equipment

• Ve hicle (trucks, A

TVs, tractors)

• Hose/reel, mechanical pump, tank46

**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 Exposure**  **(μg) Hands**  **Head Body** 

 Sum of wash samples
 Adjusted upward by a fa ctor of 2 by EP A Fa ce/neck wipe:

 Extrapolated to areas covered by protective eyewear (12 of 21)
 Extrapolated to whole head
 Adjusted upward by a f actor of 2 by EP A Sum of:
 Six WBD sections
 Sock dosimeters  Sum of front

and back OVS sections
 Adjusted by 16. 7 LPM breathing rate and pump rate48  

### 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: Dermal49 

## 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 ai50 1 - 7% contribution
11 - 84% contribution 

### MEA vs non-MEA

**Average contribution = 30%**  

## Handgun Exposure Monitoring Results: Dermal51 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: Inhalation52 

## 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 objective53



### Lognormal Probability Plots Dermal Inhalation 

## Handgun Exposure Monitoring Results: Distributional Fit54 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**  **( μ**  **g/lb ai**  **) GSD**  **M ICC**  **GM M**  **AM M**  **P95 M**  **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 = 95 th percentile  Considering data structure, lognormal mixed - model is most appropriate 

###  AM M = GM M * e (0.5*( lnGSD M ) 2 ) 

###  P95 M = GM M * GSD M (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** GM M 1.8 1.8 AM M 2.4 2.4 P95 M 2.6 2.657  

### 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 Objective58  

## 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 

## H andgun Exposure Analysis: Secondary Objective59  

## 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 Objective60 

## 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 Objective62 

## 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 context63



# 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 condition64



## Supplemental Slides65 

## Field Fortification Results – Avg Recovery Chemical x Matrix x Spike Level66 

## Field Fortification Results – Coeff . of Variation Chemical x Matrix x Spike Level67 

## Backpack Exposure Results: Additional Analyses68 

## Backpack Exposure Results: Additional Analyses69 

## Backpack Exposure Results: Additional Analyses70 

## Backpack Exposure Results: Additional Analyses71 

## Handgun Exposure Results: Additional Analyses72 

## Handgun Exposure Results: Additional Analyses73 

## Handgun Exposure Results: Additional Analyses74 

## Handgun Exposure Results: Additional Analyses75



# 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 Fe males 0 0 Completed consent process in English 17 21 Completed consent process in Spanish 2 0 Self- identified as low or limited literacy and u sed witness 1 0 Ye ars of experience 0.33 – 15 0.17 – 34 Age Range 21 – 53 19 - 68 Withdrew at own request 0 0 Re moved 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 chemical resistant 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

8788 

# 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 consent89



# 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 influence90



# 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 2691



# 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?