## Date:

Subject: 

## UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460



## July 31,2014 OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION



## Flupyradifurone. 

## Occupational and Resid entia l Ex posure Assessment for a New

Insec t icide Active Ingredient Propos ed for Use on Soybean Seeds and the Following Agricultural Crops: Brassica; 

## B ushberr ies

, except Cranberry; Cereal Grains; Citrus; Cotton; Cucurbits; Fruiting Vegetables; Hops; Leafy Vegetables; Legumes; Low Growing Berries; No n -Grass An im a l Feeds; Peanuts; Pome Fruit; Prickly Pears; Root Vegetables; Small Vine Climbing Fruit; Tree Nuts, except

A lmonds ; and Tuberous and Corm Vegetab les.

PC Code : 122304

Decision No.: 471642 

### DP Barcode: D413194 Registration Nos.: 264-RRUE, 264-

RURR

Petition No.: 2F81 0 I Regulatory Action:

Risk Assessment Type: Occupational / Residential Exposure

Ass e ssment Case No.: N A

TXRNo.:NA

MRIDNo.: NA



## From:

Through:

To: 

## Kristin Rury, Biologist 

# 'f# 9~ Risk Assessment Branc h

# III**~** 

# Q

Health E ffects Di v ision (7509P) CAS No.: 951659-40-8

40CFR:NA



## Barry O'Keefe, Senior Biologist

Risk Assessmen t Branch III

Health Effects Division (7509P)

# B.o·~

and



# .**o**

### ~~ ? 

# Lv¥.£-_)
Cassi Walls, Se nior Biologist**lC.:ft ,.....** **:** 

## Alexandra LaMay

, Biologist 

# d

Exposure Science Advisory Committee (Expo C) I 

## HED

Jessica Rogala, Risk Manager Reviewer

Insect icide Branch Registration Division (7505P)

Page I of32

## Introduction



## The Registration D ivision (RD) requested that the Health Effects Division (HED) conduct an occupational and residential e x posure and risk assessment for th e new insect icide active ingre dient

, flupyradifurone as part of a globa l joint review.



## It i s HED policy to us e the best availab l e data to assess exposure. Severa l sources of gener ic

data were used in this assessment as s urrogate data in the absence of chemical-specific data, including: th e Pesticide Hand l ers Exposure Database Version 1

. 1 (PHED 1 .1 ); th e Agricultura l

Handler Ex posure Task Force (AHETF) database; the Agricultural Reentry Task Force (ARTF)
database; and ExpoSAC Po li cy 14, 15. 1 (SOPs for Seed Treatment) and The Reviewer's Aid to Calculating Occupational Exposure From Activities Related to Agricultural Seed Treatment.

Some of th ese data are proprietary, and subject to the data protection provisions of the Fed eral

Insecticide

, Fungicide

, and Rodenticide Act (FIFRA).

Note: 

## This memorandum was reviewed by the Exposure Science Advisory Committee (ExpoSAC) on March 13, 2014.

Page 2 of32Page 3 of 32 

## Table of Co ntents

1.0 Executive Summary

................................ ................................ ................................ ............. 4

2.0 Risk Assessment Conclusions and Recommendations

................................ ........................ 6

2.1 Summary of Risk Estimates

................................ ................................ ............................. 6

2.2 Data Deficiencies and Requirements

................................ ................................ ............... 6

3.0 Hazard Characterization

................................ ................................ ................................ ....... 6

4.0 Use Profile

................................ ................................ ................................ ........................... 8

5.0 Residentia l Exposure and Risk Estimates

................................ ................................ .......... 12

5.1 Spray Drift

................................ ................................ ................................ ...................... 12

5.2 Residential Bystander Post

- Application Inhalation Exposure

................................ ....... 12

6.0 Occupational Exposure and Risk Estimates

................................ ................................ ...... 12

6.1 Occupational Handler Exposure/Risk Estimates

................................ ............................ 12

6.2.1 Occupational Post

- application Inhalation Exposure/Risk Estimates

...................... 25

6.2.2 Occupational Post

- application Dermal Exposure/Risk Estimates

.......................... 26 Appendix A. Summary of Occupational Non

- cancer Algorithms

................................ ............... 30Page 4 of 32



## 1.0 Executive Summary

The new active ingredient (ai), flupyradifurone has been proposed for use on multiple agricultural crops and as a soybean seed treatment. Flupyradifurone belongs to a new class of

chemicals known as the butenolides

, which like nicotine and neonicotinoid insecticides , bind to

nicotinic a cetylcholine receptors (nAchR) and trigger a response

.

This is the first proposed use for flupyradifurone. Bayer CropScience has proposed flupyradifurone use as a soybean seed treatment, and on the following agricultural crops/crop

groups: Brassica; bu shberries, except cranberry; cereal grains; citrus; cotton; cucurbits; fruiting vegetables; hops; leafy vegetables; legumes; low growing berries; non

- grass animal feeds; peanuts; prickly pears; pome fruit; root vegetables; small vine climbing fruit; tree n uts, except almonds; and tuberous and corm vegetables

. There are no proposed residential uses of flupyradifurone.

The proposed uses will be added to the technical product label ( Flupyradifurone TC , EPA Reg.

No. 264

- RRUG ) and to the two formulated end u se product labels ( BYI 02960 480 FS , EPA Reg. No. 264

- RRUE , and SivantoTM 200SL , EPA Reg. No. 264

- RRUR ). Both end

- use products

are liquid formulations containing 40.68% and 23.4 % flupyradifurone by weight, respectively.

Proposed Use Profile Flupyradifurone has been proposed for soybean seed treatment as a water

- based slurry , applied

with standard slurry or mist commercial seed treatment equipment

. BYI 02960 480 FS (EPA Reg. No. 264

- RRUE) may be applied as a single application at a rate of 0.045

– 0.068 mg ai/seed (0.00036

- 0.00054 lb ai/lb seed). The proposed seed treatment label ( BYI 02960 480 FS ; EPA Reg. No. 264

- RRUE) requires seed treaters and workers cleaning the treatment facilities to wear long sleeved shirts, long pants, shoes, so cks, and chemical resistant gloves. Baggers and others involved in the packaging of treated seed are required to wear long sleeved shirts, long pants,

shoes

, and socks.

SivantoTM (EPA Reg. No. 264

- RRUR) may be applied to the proposed agricultural crops via ground, aerial, or chemigation equipment. The proposed single application rates range from 7.0

– 28 fl oz/A (0.091

– 0.365 lb ai/A), with a maximum seasonal application rate of 0.365 lb ai/A. The proposed SivantoTM label requires occupational handlers to wear long sleeved shirts, long pants, shoes, socks, and chemical resistant gloves. The proposed restricted entry interval (REI)

is four hours.

Exposure Profile Based on application rate and label information, only short

- and intermediate

- term expos ure is expected for occupational handlers and post

- application workers. Chronic exposure is not expected for the proposed use pattern s

.

Hazard Concerns With repeated dosing, reductions in body weight with associated decreases in body weight gains

and food consumption were commonly seen in various studies and in all species of test animals (rats, mice, dogs

, and rabbits). The liver and thyroid were also common targets ofPage 5 of 32



## flupyradifurone toxicity. The database appears to suggest that dogs are more sen sitive to the effects of flupyradifurone; however, w ith body weight adjustments , the dog and rat are almost equally as sensitive in response to flupyradifurone toxicity. In dogs

, flupyradifurone produced skeletal muscle atrophy/degeneration at doses substantially lower than those producing liver, thyroid

, and body weight effects

. Flupyradifurone is classified as “not likely to be carcinogenic

to humans .” Flupyradifurone exhibits low acute mammalian toxicity via oral, dermal

, and

inhalation routes o f exposure (Category III or IV for acute lethality and irritation studies) and is

not a dermal irritant or sensitizer. The Agency waived the requirement for the subchronic inhalation toxicity stud y (TXR# 0056903 ). HED presently has sufficient information to evaluate the hazards associated with exposure to flupyradifurone at this time.

Occupational Handler Exposures and Risk Estimates There are no occupational handler risk estimates of concern for the proposed uses of flupyradifurone at baseline (no per sonal protective equipment; PPE). The level of concern (LOC) for occupational handler risk is a margin of exposure (MOE) < 100. For the agricultural uses of flupyradifurone, the short

- and intermediate

- term combined (dermal + inhalation) occupational han dler margins of exposure ( MOEs ) ranged from 260 to 95 ,000 with baseline PPE (Table 6.1.1). With the addition of gloves, as required on the flupyradifurone label, the short

and intermediate

- term combined (dermal + inhalation) occupational handler MOEs ran ged from

800 to 95 ,000 (Table 6.1.2). For the proposed seed treatment use of flupyradifurone (Table 6.1.3), the combined (dermal + inhalation) short

- and intermediate

- term MOEs ranged from 2,000 to 14,000.

Occupational Post

- Application Exposures and Risk Estimates The LOC for occupational post

- application risk is a MOE < 100. The occupational short

- term
post

- application risk estimates resulted in dermal MOEs of > 170 on the day of application and

w ere not of concern.

Based on the Agency's curre nt practices, a quantitative occupational post

- application inhalation exposure assessment was not performed for flupyradifurone at this time. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational
post

- application inhalation exposure assessment for flupyradifurone

.

Human Studies Review This risk assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical. These data, whi ch include studies from

PHED 1.1 ; the Agricultural Handler Exposure Task Force (AHETF) database; ARTF database; and ExpoSAC Policy 14 , 15.1 (SOPs for Seed Treatment) and The Reviewer’s Aid to Calculating Occupational Exposure From Activities Related to Agr icultural Seed Treatment ; are (1) subject to ethics review pursuant to 40 CFR 26, (2) have received that review, and (3) are compliant with applicable ethics requirements. For certain studies, the ethics review may have included review by the Human Studie s Review Board. Descriptions of data sources, as well as guidance on their use, can be found at the Agency website 1



## .

1 

### http://www.epa.gov/pesticides/science/handler

- exposure

- data.html and http://www.epa.gov/pestici des/science/post

- app

- exposure

- data.htmlPage 6 of 32



## 2.0 Risk Assessment Conclusions and Recommendations

There were no risk estimates of concern for occupational handlers of flupyradifurone at baseline (no PPE), nor were there any occupational post

- application risk estimates of concern on day 0 from the proposed uses of flupyradifurone.

2.1 Summary of Risk Estimates

For the agricultural uses of flupyradifurone, the short

- and intermediate

- term combined (dermal + inhalation) occupational handler MOEs ranged from 260 to 95 ,000 with baseline PPE (Table 6.1.1). With the addition of gloves, as required on the f lupyradifurone label, the short

- and

intermediate

- term combined (dermal + inhalation) occupational handler MOEs ranged from 800

to 95 ,000 (Table 6.1.2). For the proposed seed treatment use of flupyradifurone (Table 6.1.3), the combined (dermal + inhalatio n) short

- and intermediate

- term MOEs ranged from 2,000 to 14,000. The occupational short

- term post

- application risk estimates resulted in dermal MOEs of

> 170 on the day of application and w ere not of concern.

2. 2 Data Deficiencies and Requirements

Since the highest estimated occupational post

- application exposure using default dislodgeable foliar residue (DFR) values is not minimal in comparison to the level of concern (i.e., the calculated MOE is not greater than 2 times higher than the level of concern, MOE = 170 compared to the LOC of 1 00); t herefore, EPA is requiring the 40CFR DFR data requirement to facilitate any necessary exposure assessments refinements and to further EPA’s general understanding of the availability of dislodgeable foliar pesticide residues.

3 .0 Hazard Characterizat ion

A full description of the flupyradifurone toxicological profile can be found in the corresponding risk assessment (D407063).

Acute Toxicity Flupyradifurone is classified as “not likely to be carcinogenic to humans .” Flupyradifurone

exhibits low acut e mammalian toxicity via oral, dermal, and inhalation routes of exposure (Category III or IV for acute lethality and irritation studies) and is not a dermal irritant or

sensitizer.

Table 3.1. Acute Toxicity Profile

– Flupyradifurone.

OPPTS

Guideline No. Study Type MRID Results Toxicity Category

870.1000 Acute Oral

- rat 48844101 LD 50 cut off ≥ 2000 mg/kg (HDT) 1/3 death In ACN 2/12 test animals died at 800 mg/kg III

870.1200 Acute Dermal

- Rabbit 48844104 LD 50 > 2 000 mg/kg III

870.1300 Acute Inhalation

- Rat 48844105 LC 50 > 4671 mg/m 3 ( 4.67 mg/L) IVPage 7 of 32

Table 3.1. Acute Toxicity Profile

– Flupyradifurone.

OPPTS

Guideline No. Study Type MRID Results Toxicity Category

870.2400 Primary Eye Irritation

-

Rabbit 48844106 Redness of the conjunctivae, reversed within 48 hours (score 2) IV

870.2500 Primary Dermal

Irritation

- Rabbit 48844107 Non

- irritating IV

870.2600 Dermal Sensitization

-

mouse 48844108 Non

- sensitizing NA



## Toxicological P oints of Departure (P ODs ) Used for Risk Assessment With repeated dosing, reductions in body weight with associated decreases in body weight gains and food consumption were commonly seen in various studies and in all species of the test animals (rats, mice, dogs

, and rabbits). The liver and thyroid were also common targets of flupyradifurone toxicity. With adjusting for body weight (body weight 3⁄4 scaling factor), the dog

ap pears to be the most sensitive species to flupyradifurone. In dogs

, flupyradifurone produced skeletal muscle atrophy/degeneration at doses substantially lower than those producing liver, thyroid, and body weight effects

. Flupyradifurone is classified as “not likely to be carcinogenic

to humans .”

Estimated short

- and intermediate

- term dermal and inhalation exposures were compared to an oral point of departure ( POD ) based on effects seen in two co

- critical studies: (1) skeletal muscle myofiber atrophy/degeneration, decreases in body weight towards the end of the study (7

- 9%), and decreased body weight gain in males seen at the lowest observed adverse effect level ( LOAEL ) of 28 mg/kg/day in the 90

- day dog oral study ; and (2) pup body weight decre ase seen at the LOAEL of 38.7 mg/kg/day in the 2

- generation rat reproductive toxicity study ( no observed adverse effect level; NOAEL = 12 mg/kg/day) . The Food Quality Protection Act (FQPA) safety factor has been reduced (i.e., from 10X to 1X). The level of concern (LOC) for dermal and inhalation risk assessment is a MOE of 100 (i.e. an MOE < 100 is of concern).

Table 3.2. Su mmary of Toxicological Doses and Endpoints for use in Flupyradifurone Occupational Human Health Risk

Assessments

. Exposure

Scena rio Point of Departure

(POD) Uncertainty /

FQPA Safety

Factors RfD, PAD, Level of

Concern for Risk

Assessment Study and Toxicological Effects

Dermal

Short

- (1

- 30 days) and

intermediate

terms (1

- 6 months) NOAEL = 12 mg/kg/day

7.42% dermal absorption factor UF A = 10x

UF H =10x

FQPA SF= 1x LOC = 100 1

- year oral toxicity study

- dog LOAEL= 28 mg/kg/day based on minimal to slight, focal to multifocal areas of skeletal muscle degeneration in grastrocnemius and/or biceps

femoris muscle.

2

- generation reproduction study

- rat

as a co

- critical study.

NOAEL= 7.7 Offspring LOAEL=38.7 mg/kg/day based on pup body decease.

Inhalation

Short

- (1

- 30 days) and

intermediate

NOAEL = 12 mg/kg/day UF A = 10x

UF H =10x

FQPA SF= 1x LOC = 100 1

- year oral toxicity study

- dog LOAEL= 28 mg/kg/day based on minimal to slight, focal to multifocal areas of skeletal muscle degenerationPage 8 of 32

Table 3.2. Su mmary of Toxicological Doses and Endpoints for use in Flupyradifurone Occupational Human Health Risk

Assessments

. Exposure

Scena rio Point of Departure

(POD) Uncertainty /

FQPA Safety

Factors RfD, PAD, Level of

Concern for Risk

Assessment Study and Toxicological Effects

terms (1

- 6 months) in grastrocnemius and/or biceps

femoris muscle.

2

- generation reproduction study

- rat

as a co

- critical study.

NOAEL= 7.7 Offspri ng LOAEL=38.7 mg/kg/day based on pup body decease. Cancer (oral, dermal, and inhalation) Classification : 

### Classification: “Not likely to be Carcinogenic to Humans” based on data showing no

treatment

- related increase in tumors incidence in rat and mouse carcinogenicity studies. N o mutagenic concern was reported in the genotoxicity studies.
Point of Departure (POD) = A data point or an estimated point that is derived from observed dose

- response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). U F H = potential variation in sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern.



## Absorption : A dermal absorption factor of 7.42 % was used for the exposure assessment and is

based on 24

- hour measurements of dermal absorption in in vivo and in vitro dermal absorption

studies . Since no inhalation absorption data are available, toxicit y by the inhalation route is considered to be equivalent to the estimated toxicity by the oral route of exposure.

Body Weight : The standard body weight for the general population (80 kg) was used for all exposure scenarios covered in this risk assessmen t since the endpoints selected were not developmental and/or fetal effects.

4 .0 Use Profile

A summary of the proposed use pattern of flupyradifurone is shown in Table 4.0.Page 9 of 32

Table 4.0. Summary of Directions for the Proposed Uses of Flupyradifurone.

Crop Application Method(s) Maximum

Application

Rate

( fl oz/A ) Maximum

Application

Rate

( lb ai/A ) Maximum

Seasonal Application Rate (lb ai/A) PHI

(days) RTI

(days) Minimum

Application Volumes (gal/A) Notes

SivantoTM 200 SL (1.67 lb ai/gal)

Crop Group 15

– Cereal Grains (except Rice)

Ground, Aerial, Chemigation 14.0 0.18 0.365 7 (forage or sweet corn) ; 21 (dried grain, stover or straw) 7

Ground: 10 gal/A,

Aerial: 2 gal/A Cotton 14 14

Crop Group 18

– Non

Grass Animal Feeds (Forage, Fodder, Straw, Hay) 7 (forage, silage, cutting for hay or seed of alfalfa, lespedeza, sainfoin)

14 for all others 10 Clover only in ID, OR, WA

Peanuts 7 10

Crop Subgroup 1B

– Root Vegetables (except Sugarbeet) 7 10

Crop Subgroup 1C

– Tuberous and Corm Vegetables 7 7 Control CO Potato Beetle only west of Mississippi River Only

Crop Group 4

– Leafy Vegetables (except Brassica) 1 7

Crop Group 5

- Brassica Cole Leafy Vegetables 1 7

Crop Group 6

– Legume Vegetables 14.0 0.18 0.365 7 (forage, leaves, vines, pods, cutting for hay, or seed (except dry soybean seed); 21 for dry soybean seeds 10

Foliar Application: Crop Group 8

- 10

– Fruiting Vegetables Ground, Aerial 14.0 0.18 0.365 1 7 Control CO Potato Beetle only west of Mississippi River Only.Page 10 of 32

Table 4.0. Summary of Directions for the Proposed Uses of Flupyradifurone.

Crop Application Method(s) Maximum

Application

Rate

( fl oz/A ) Maximum

Application

Rate

( lb ai/A ) Maximum

Seasonal Application Rate (lb ai/A) PHI

(days) RTI

(days) Minimum

Application Volumes (gal/A) Notes

Soil Application Crop Group 8

- 10

– Fruiting Vegetables Chemigation

, Injection, Potting Hole

Drench at Transplanting,

Post

- Transplant Drench,

Handheld 28.0 0.365 0.365 45 N/A N/A

Foliar Application: Crop Group 9

– Cucurbit Vegetables Ground, Aerial 14.0 0.18 0.365 1 7 Ground: 10 gal/A,

Aerial: 2 gal/A Control CO Potato

Beetle only west of Mississippi River

Soil Application: Crop Group 9

– Cucurbit Vegetables Chemigation, Injection, Potting Hole

Drench at Transplanting,

Post

- Transplant Drench,

Handheld 28.0 0.365 0.365 21 N/A N/A

Hops Ground, Aerial,

Airblast 10.5 0.14 0.137 21 N/A Ground: 25 gal/A,

Aerial: 10 gal/A

Foliar: Crop Group 10

- 10

– Citrus Ground, Aerial,

Airblast 14.0 0.18 0.365 1 10 Asian citrus psyllid: Ground: 2.5 gal/A,

Aerial: 2 gal/A

For other pests: adjust application

volume to ensure adequate

coverage

Soil: Crop Group 10

- 10

– Citrus Chemigation,

Basal Drench,

Handheld 28.0 0.365 0.365 30 N/A N/APage 11 of 32

Table 4.0. Summary of Directions for the Proposed Uses of Flupyradifurone.

Crop Application Method(s) Maximum

Application

Rate

( fl oz/A ) Maximum

Application

Rate

( lb ai/A ) Maximum

Seasonal Application Rate (lb ai/A) PHI

(days) RTI

(days) Minimum

Application Volumes (gal/A) Notes

Crop Group 11

- 10

– Pome Fruit Ground, Aerial, Chemigation, Airblast,

Handheld 14.0 0.18 0.365 14 10 Ground: 25 gal/A,

Aerial: 10 gal/A

Crop Subgroup 13

- 07B

– Bushberries (except cranberry) Ground, Aerial, Chemigation, Airblast,

Handheld 14.0 0.18 0.365 3 7 Ground: 25 gal/A,

Aerial: 10 gal/A

Crop Subgroup 13

- 07G

– Low Growing Berries Ground, Aerial, Chemigation,

Handheld 14.0 0.18 0.365 0 10 Ground: 25 gal/A,

Aerial: 10 gal/A

Foliar: Crop Subgroup

13

- 07F

– Small Fruit Vine Climbing (except fuzzy kiwifruit) Ground, Aerial, Chemigation,

Airblast 14.0 0.18 0.365 1 10 Ground: 25 gal/A,

Aerial: 10 gal/A

Soil: Crop Subgroup

13

- 07F

– Small Fruit Vine Climbing (except fuzzy kiwifruit) Chemigation

Into Root Zone, Basal Drench,

Handheld 28.0 0.365 0.365 30 N/A N/A

Crop Group 14

– Tree Nuts (except Almonds) Ground, Aerial, Chemigation, Airblast,

Handheld 14.0 0.18 0.365 7 14 Ground: 25 gal/A,

Aerial: 10 gal/A

Prickly Pear/Cactus

Pear Ground, Chemigation,

Handheld 14.0 0.18 0.365 14 7 Ground: 75 gal/A Do not apply via aerial application

BYI 02960 480 FS (4 lb ai/gal)

Soybean Seeds Commercial

Seed Treatment Equipment 1.44 fl

oz/cwt 0.068 mg

ai/seed 0.00054 lb

ai/lb seedPage 12 of 32



## 5 .0 Residential Exposure and Risk Estimates

There are no proposed or registered residential uses of flupyradifurone at this time ; therefore, a residential exposure assessment has not been conducted.

5 .1 Spray Drift

Spray drift is a potential source of exposure to those nearby pesticide applications. This is particularly the case with aerial application, but, to a lesser extent, spray drift can also be a potential source of exposure from the ground application methods (e.g., groundbo om and airblast) employed for flupyradifurone . The Agency has been working with the Spray Drift Task Force (a task force composed of various registrants which was developed as a result of a Data

Call

- In issued by EPA), EPA Regional Offices and State Lead Agencies for pesticide regulation and other parties to develop the best spray drift management practices (see the Agency’s Spray Drift website for more information). 2 

## The Agency is also taking means to qualitatively and qualitatively address spray drift as a potential source of exposure in risk assessments for pesticides through existing programs such as Ag Drift and chemical specific properties of pesticides. The potential for spray drift will be quantitatively evaluated for each pesticide during

the Re gistration Review process which ensures that all uses for that pesticide will be considered concurrently.

5

. 2 Residential Bystander Post

- Application Inhalation Exposure

Based on the Agency's current practices, a quantitative post

- application inhalation exposure assessment was not performed for flupyradifurone at this time primarily because of the low acute inhalation toxicity (Toxicity Category IV), low vapor pressure ( 7. 0 x 10

- 9 

## mm Hg at 20 o 

## C ), and the low proposed use rate (0. 365 lb ai/A). However, volatilization of pesticides may be a source of post

- application inhalation exposure to individuals nearby pesticide applications. The Agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 3



## . The Agency is in the process of

evaluat ing the SAP report and may, as appropriate, develop policies and procedures to identify the need for and, subsequently, the way to incorporate post

- application inhalation exposure into the Agency's risk assessments. If new policies or procedures are devel oped, the Agency may revisit the need for a quantitative post

- application inhalation exposure assessment for flupyradifurone

.

6 .0 Occupational Exposure and Risk Estimates

6 .1 Occupational Handler Exposure/Risk Estimates

HED uses the term handlers to describe those individuals who are involved in the pesticide application process. HED believes that there are distinct job functions or tasks related to applications and exposures can vary depending on the specifics of each t ask. Job requirements

2 

### Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm

3 

### Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.htmlPage 13 of 32



## (amount of chemical used in each application), the kinds of equipment used, the target being treated, and the level of protection used by a handler can cause exposure levels to differ in a manner specific to each application event.

Based on the anticipated use patterns and current labeling, types of equipment and techniques that can potentially be used, occupational handler exposure is expected from the proposed uses. The quantitative exposure/risk assessment developed for occupat ional handlers is based on the following scenarios:

 Mixing/Loading liquid formulations for aerial , airblast, chemigation, and groundboom application;

 Applying sprays with aerial , airblast, and groundboom equipment;

 F lagging for aerial applications;

 Mix ing/Loading/Applying using a backpack sprayer and mechanically pressurized handgun ;

 Primary handling for seed treatment (loading/applying, sewing, bagging treated seed; multiple activities); and

 Secondary handling for seed treatment (planters).

Occupatio nal Handler Exposure Data and Assumptions A series of assumptions and exposure factors served as the basis for completing the occupational handler risk assessments. Each assumption and factor is detailed below on an individual basis.

Application Rate : A summary of the proposed application rates is provided in Table 4.0.

Unit Exposures : It is the policy of HED to use the best available data to assess handler exposure. Sources of generic handler data, used as surrogate data in the absence of chemical

- sp ecific data, include PHED 1.1, the AHETF database, or other registrant

- submitted occupational exposure studies. Some of these data are proprietary (e.g., AHETF data), and subject to the data protection provisions of FIFRA. The standard values recommended for use in predicting handler exposure that are used in this assessment, known as “unit exposures”, are outlined in the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table 4 

## ”, which, along with additional information on HED policy on us e of surrogate data, including descriptions of the various sources, can be found at the Agency website 5



## . The standard values recommended for use in predicting handler exposure that are used in this assessment, known as “unit exposures”, for

seed treatment activities are outlined in the SO P 14.

Area Treated or Amount Handled : Based on HED ExpoSAC Policy 9.1, the amount treated or handled per day was assumed to be:

 1200 acres for mixing/loading and applying with aerial application equipment to high

acreage crops ;

 350 acres for mixing/loading and applying with aerial and application to typical field

crops;

 350 acres for mixing/loading for chemigation application;

4 

### Available: http://www.epa.gov/opp00001/science/handler

- exposure

- table.pdf

5 

### Available: http://www.epa.gov/pesticides/science/handler

- exposure

- data.htmlPage 14 of 32



##  350 acres for flagging for aerial application;

 200 acres for mixing/loading and applying with groundboom application equipment to high acreage crops ;

 80 acres for mixing/loading and applying with groundboom application equipment to typical field crops;

 40 acres for mixing/loading and applying with airblast application equipment to orchards;

 40 gallons for mixing/loading/applying using backpack application equipment to orchard floors;

 1000 gallons for mixing/loading/applying using mechanically pressurized handgun equipment for broadcast and foliar application to orchards and typica l field cro ps;

 28,1250 lbs of treated seed per day for loaders, applicators, baggers, sewers of treated seed, and other multiple activities for seed treatment; and

 1,111 lbs of treated seed planted per day.

Exposure Duration : HED classifies exposures from 1 to 30 days as short

- term and exposures 30 days to six months as intermediate

- term. Exposure duration is determined by many things, including the exposed population, the use site, the pest pressure triggering the use of the pesticide, and the cultural practices surrounding that use site. For most agricultural uses, it is reasonable to believe that occupational handlers will not apply the same chemical every day for

more than a one

- month time frame; however, there may be a large agribusiness and/or commercial app licators who may apply a product over a period of weeks (e.g., completing multiple applications for multiple clients within a region).

For flupyradifurone , based on the proposed use, short

- and intermediate

- term exposures are expected. Many of the prop osed crops are grown on large

- scale farms and it is likely that a commercial applicator could apply flupyradifurone over a longer period of time. While the number of days treating the proposed soybean seed crops could potentially exceed the typical

interm ediate

- term duration used in HED’s occupational assessments, HED ha s no information to
indicat e that the same chemical is used consecutively for a long

- term duration . Therefore, chronic occupational handler exposure for seed treatment was not assessed

.

Additionally, for both dermal and inhalation exposures, the PODs selected are considered protective of both short

- and intermediate

- term durations.

Mitigation/Personal Protective Equipment : Estimates of dermal and inhalation exposure were calculated for various levels of PPE. Results are presented for “baseline,” defined as a single layer of clothing consisting of a long sleeved shirt, long pants, shoes plus socks, no protective gloves, and no respirator, as well as baseline with various levels of PPE as necessary (e.g., gloves, respirator, etc). The proposed BYI 02960 480 FS (EPA Reg. No. 264

- RRUE) label requires seed treaters and workers cleaning the treatment facilities to wear long sleev ed shirts, long pants, shoes, socks, and chemical resistant gloves. Baggers and others involved in the packaging of treated seed are required to wear long sleeved shirts, long pants, shoes

, and socks. The proposed SivantoTM (EPA Reg. No. 264

- RRUR) label r equires occupational handlers to

wear long sleeved shirts, long pants, shoes, socks, and chemical resistant gloves.Page 15 of 32



## Occupational Handler Non

- Cancer Exposure and Risk Estimate Equations The algorithms used to estimate non

- cancer exposure and dose for o ccupational handlers can be found in Appendix A

.

Combining Exposures/ Risk Estimates

Dermal and inhalation risk estimates were combined in this assessment, since the toxicological effects for these exposure routes were similar. Dermal and inhalation risk estimates were combined using the following formula:

Total MOE = Point of Departure (mg/kg/day) ÷ Combined dermal + inhalation dose (mg/kg/day)



## Summary of Occupational Handler Non

- Cancer Exposure and Risk Estimates

There are no ris k estimates of concern at baseline (no PPE). For the agricultural uses of flupyradifurone, the short

- and intermediate

- term combined (dermal + inhalation) occupational

handler MOEs ranged from 260 to 17,000 with baseline PPE (Table 6.1.1) . With the addit ion of gloves, as required on the flupyradifurone label, the short

- and intermediate

- term combined (dermal + inhalation) occupational handler MOEs ranged from 800 to 57,000 (Table 6.1.2) . For the proposed seed treatment use of flupyradifurone (Table 6.1.3 ) , the combined (dermal + inhalation) short

- and intermediate

- term MOEs ranged from 2,000 to 14,000.

The Agency matches quantitative occupational exposure assessment with appropriate characterization of exposure potential. While HED presents quantitativ e risk estimates for human flaggers where appropriate, agricultural aviation has changed dramatically over the past two decades. According the 2012 National Agricultural Aviation Association (NAAA) survey of their membership, the use of GPS for swath guida nce in agricultural aviation has grown steadily from the mid 1990’s. Over the same time period, the use of human flaggers for aerial pesticide applications has decreased steadily from ~15% in the late 1990’s to only 1% in the most recent (2012) NAAA survey . The Agency will continue to monitor all available information sources to best assess and characterize the exposure potential for human flaggers in agricultural aerial applications.

HED has no data to assess exposures to pilots using open cockpits. The only data available is for exposure to pilots in enclosed cockpits. Therefore, risks to pilots are assessed using the engineering control (enclosed cockpits) and baseline attire (long

- sleeve shirt, long pants, shoes, and socks); per the Agency’s Worker Protection Standard stipulations for engineering controls, pilots are not required to wear protective gloves for the duration of the application . With this level of protection, there ar e no risk estimates of concern for applicators.Page 16 of 32

Table 6 .1. 1. Occupational Handler Non

- Cancer Exposure and Risk Estimates for Flupyradifurone with Baseline Attire

.

Exposure Scenario Crop or Target Level of

Concern Dermal Unit

Exposure (μg/lb ai) 1 Inhalation Unit

Exposure (μg/lb ai) 1 Maximum

Application

Rate 2 Area

Treated or

Amount

Handled Daily 3 Dermal Inhalation Total

Baseline Baseline Dose (mg/kg/day) 4 MOE 5 Dose (mg/kg/day) 6 MOE 7 MOE 8

Mixer/Loader

Mixing/Loading Liquids for Aerial Application Crop Group 10

- 10

(Citrus), Crop Group

11

- 10 (Pome Fruit), Crop Group 13

- 07B (Bushberries, Highbush), Crop Group 14 (Tree Nuts, Except Almonds) 100 220 0.219 0.18 lb ai/A 350 acres 0.0129 930 0.000173 69,000 920

Hops 100 220 0.219 0.14 lb ai/A 350 acres 0.010 1,200 0.000134 90,000 1,200

Field crop, typical 9 100 220 0.219 0.18 lb ai/A 350 acres 0.0129 930 0.000173 69,000 920

Crop Group 15 (Cereal Grains), Cotton, Crop Group 18 (Alfalfa & Forage Crops), Peanuts, Crop Subgroup 1C, Crop Group 6 (Legume Vegetables) 100 220 0.219 0.18 lb ai/A 1200 acres 0.0441 270 0.000591 20,000 270

Mixing/Loading for Airblast Application Crop Group 10

- 10

(Citrus), Crop Group

11

- 10 (Pome Fruit), Crop Group 13

- 07B (Bushberries, Highbush), Crop Group 14 (Tree Nuts, Except Almonds) 100 220 0.219 0.18 lb ai/A 40 acres 0.00147 8,200 0.0000198 610,000 8,100

Hops 100 220 0.219 0.14 lb ai/A 40 acres 0.00114 11,000 0.0000154 780,000 11,000

Mixing/Loading for Chemigation Application Soil Directed: Crop

Group 10

- 10 (Citrus), Crop Group 11

- 10 (Pome Fruit), Crop Group 13

- 07B (Bushberries, Highbush), Crop Group 14 (Tree Nuts, Except Almonds) 100 220 0.219 0.365 lb ai/A 350 acres 0.0261 460 0.000350 34,000 450Page 17 of 32

Table 6 .1. 1. Occupational Handler Non

- Cancer Exposure and Risk Estimates for Flupyradifurone with Baseline Attire

.

Exposure Scenario Crop or Target Level of

Concern Dermal Unit

Exposure (μg/lb ai) 1 Inhalation Unit

Exposure (μg/lb ai) 1 Maximum

Application

Rate 2 Area

Treated or

Amount

Handled Daily 3 Dermal Inhalation Total

Baseline Baseline Dose (mg/kg/day) 4 MOE 5 Dose (mg/kg/day) 6 MOE 7 MOE 8

Broadcast: Field crop, typical 9 100 220 0.219 0.18 lb ai/A 350 acres 0.0129 930 0.000173 69,000 920

Soil Directed: Field Crop Typical 9 100 220 0.219 0.365 lb ai/A 350 acres 0.0261 460 0.000350 34,000 450

Broadcast: Crop Group 15 (Cereal Grains), Cotton, Crop Group 18 (Alfalfa & Forage Crops), Peanuts, Crop Subgroup 1C, Crop Group 6 (Legume Vegetables) 100 220 0.219 0.18 lb ai/A 350 acres 0.0129 930 0.000173 69,000 920

Mixing/Loading for

Groundboom Application Broadcast: Field Crop

Typical 9 100 220 0.219 0.18 lb ai/A 80 acres 0.00294 4,100 0.0000394 300,000 4,000

Soil Directed: Field Crop Typical 9 100 220 0.219 0.365 lb ai/A 80 acres 0.00595 2,000 0.0000799 150,000 2,000

Broadcast: Crop Group 15 (Cereal Grains), Cotton, Crop Group 18 (Alfalfa & Forage Crops), Peanuts, Crop Subgroup 1C, Crop Group 6 (Legume Vegetables) 100 220 0.219 0.18 lb ai/A 200 acres 0.00735 1,600 0.0000985 120,000 1, 600

Applicator

Aerial Application Crop Group 10

- 10

(Citrus), Crop Group

11

- 10 (Pome Fruit), Crop Group 13

- 07B (Bushberries, Highbush), Crop Group 14 (Tree Nuts, Except Almonds) 100 2.08 0.0049 0.18 lb ai/A 350 acres 0.000122 98,000 0.00000386 3,100,000 95,000

Hops 100 2.08 0.0049 0.14 lb ai/A 350 acres 0.0000946 130,000 0.0000030 4,000,000 130,000

Broadcast: Field crop, typical 9 100 2.08 0.0049 0.18 lb ai/A 350 acres 0.000122 98,000 0.00000386 3,100,000 95,000Page 18 of 32

Table 6 .1. 1. Occupational Handler Non

- Cancer Exposure and Risk Estimates for Flupyradifurone with Baseline Attire

.

Exposure Scenario Crop or Target Level of

Concern Dermal Unit

Exposure (μg/lb ai) 1 Inhalation Unit

Exposure (μg/lb ai) 1 Maximum

Application

Rate 2 Area

Treated or

Amount

Handled Daily 3 Dermal Inhalation Total

Baseline Baseline Dose (mg/kg/day) 4 MOE 5 Dose (mg/kg/day) 6 MOE 7 MOE 8

Crop Group 15 (Cereal Grains), Cotton, Crop Group 18 (Alfalfa & Forage Crops), Peanuts, Crop Subgroup 1C, Crop Group 6 (Legume Vegetables) 100 2.08 0.0049 0.18 lb ai/A 1200 acres 0.000416 29,000 0.0000133 900,000 28,000

Airblast Application Crop Group 10

- 10

(Citrus), Crop Group

11

- 10 (Pome Fruit), Crop Group 13

- 07B (Bushberries, Highbush), Crop Group 14 (Tree Nuts, Except Almonds) 100 1

, 770 4.71 0.18 lb ai/A 40 acres 0.0118 1,000 0.000424 28,000 970

Hops 100 1

, 770 4.71 0.14 lb ai/A 40 acres 0.00919 1,300 0.00033 36,000 1,300

Groundboom Application Broadcast: Field crop, typical 9 100 78.6 0.34 0.18 lb ai/A 80 acres 0.00105 11,000 0.0000613 200,000 10,000

Soil Directed: Field crop, typical 9 100 78.6 0.34 0.365 lb ai/A 80 acres 0.00213 5,600 0.000124 97,000 5,300

Crop Group 15 (Cereal Grains), Cotton, Crop Group 18 (Alfalfa & Forage Crops), Peanuts, Crop Subgroup 1C, Crop Group 6 (Legume Vegetables) 100 78.6 0.34 0.18 lb ai/A 200 acres 0.00262 4,600 0.000153 78,000 4,300

Flagger

Flagger for Aerial Hops 100 11 0.35 0.14 lb ai/A 350 acres 0.00050 24,000 0.000215 56,000 17,000Page 19 of 32

Table 6 .1. 1. Occupational Handler Non

- Cancer Exposure and Risk Estimates for Flupyradifurone with Baseline Attire

.

Exposure Scenario Crop or Target Level of

Concern Dermal Unit

Exposure (μg/lb ai) 1 Inhalation Unit

Exposure (μg/lb ai) 1 Maximum

Application

Rate 2 Area

Treated or

Amount

Handled Daily 3 Dermal Inhalation Total

Baseline Baseline Dose (mg/kg/day) 4 MOE 5 Dose (mg/kg/day) 6 MOE 7 MOE 8

Application Crop Group 10

- 10

(Citrus), Crop Group

11

- 10 (Pome Fruit), Crop Group 13

- 07B (Bushberries, Highbush), Crop Group 14 (Tree Nuts, Except Almonds)

, Field crop, typical 9

, Crop Group 15 (Cereal Grains), Cotton, Crop Group 18 (Alfalfa & Forage Crops), Peanuts, Crop Subgroup 1C, Crop Group 6 (Legume Vegetables) 100 11 0.35 0.18 lb ai/A 350 acres 0.00643 19,000 0.00027 6 43,000 13,000

Mixer/loader/Applicator

Backpack Sprayer Ground/Soil Directed:

Crop Group 10

- 10 (Citrus) 100 8

, 260 2.58 0.0365 lb ai/gal 40 gallons 0.0112 1,100 0.0000471 250,000 1,100

Mechanically Pressurized Handgun Broadcast: Crop Group

10

- 10 (Citrus), Crop Group 11

- 10 (Pome Fruit), Crop Group 13

- 07B (Bushberries, Highbush), Crop Group 14 (Tree Nuts, Except Almonds) 100 1,300 3.9 0.0365 lb ai/gal 1,000 gallons 0.0441 270 0.00178 6,700 260

Ground/Soil Directed: Crop Group 10

- 10 (Citrus) 100 1,300 3.9 0.0365 lb ai/gal 1,000 gallons 0.0441 270 0.00178 6,700 260

Broadcast: Field crop, typical 9 100 1,300 3.9 0.0365 lb ai/gal 1,000 gallons 0.0441 270 0.00178 6,700 260

Soil Application: Field crop, typical 9 100 1,300 3.9 0.0365 lb ai/gal 1,000 gallons 0.0441 270 0.00178 6,700 260

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” ( May 2013 ); Level of mitigation: Baseline. *Aerial Application is assessed assuming a closed cockpit (engineering controls).

2 Based on proposed label (Reg. No. SivantoTM (EPA Reg. No. 264

- RRUR ) )

. 3 Exposure Science Advisory Council Policy #9.1.Page 20 of 32

4 Dermal Dose = Dermal Unit Exposure ( μ g/lb ai) × Conversion Factor (0.001 mg/ μ g) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) × DAF ( 7.42 %) ÷ BW ( 80 kg).

5 Dermal MOE = Dermal NOAEL (mg/kg/day) ÷ Dermal Dose (mg/kg/day).

6 Inhalation Dose = Inhalation Unit Exposure ( μ g/lb ai) × Conversion Factor (0.001 mg/ μ g) × Application Rate (lb a i/acre or gal) × Area Treated or Amount Handled (A or gal/day) ÷ BW ( 80 kg).

7 Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

8 Total MOE = NOAEL ( 12 mg/kg/day) ÷ ( Dermal Dose + Inhalation Dose )

. 9 Crop Subgroup 1B (except sugarbeet), Crop Group 4 (Leafy Vegetables, except Brassica ), Crop Group 5 ( Brassica Cole Leafy Vegetables), Foliar Application to Crop Group 8

- 10 (Fruiting Vegetables), Foliar Application Crop Group 9 (Cucurbit Vegetables), Crop G roup 13

- 07B (Bushberries, lowbush), Crop Subgroup 13

- 07G (Low Growing Berries)

.

Table 6.1. 2 . Occupational Handler Non

- Cancer Exposure and Risk Estimates for Flupyradifurone with Label

- Specified PPE (Gloves)

.

Exposure Scenario Crop or Target Level of

Concern Dermal Unit

Exposure (μg/lb ai) 1 Inhalation Unit

Exposure (μg/lb ai) 1 Maximum

Application

Rate 2 Area

Treated or

Amount

Handled Daily 3 Dermal Inhalation Total

Gloves Baseline Dose (mg/kg/day) 4 MOE 5 Dose (mg/kg/day) 6 MOE 7 MOE 8

Mixer/Loader

Mixing/Loading Liquids for Aerial Application Crop Group 10

- 10

(Citrus), Crop Group

11

- 10 (Pome Fruit), Crop Group 13

- 07B (Bushberries, Highbush), Crop Group 14 (Tree Nuts, Except Almonds) 100 37.6 0.219 0.18 lb ai/A 350 acres 0.0022 5,500 0.000173 69,000 5,100

Hops 100 37.6 0.219 0.14 lb ai/A 350 acres 0.00177 7,000 0.000134 90,000 6,500

Field crop, typical 9 100 37.6 0.219 0.18 lb ai/A 350 acres 0.00220 5,500 0.000173 69,000 5,100

Crop Group 15 (Cereal Grains), Cotton, Crop Group 18 (Alfalfa & Forage Crops), Peanuts, Crop Subgroup 1C, Crop Group 6 (Legume Vegetables) 100 37.6 0.219 0.18 lb ai/A 1200 acres 0.00753 1,600 0.000591 20,000 1,500

Mixing/Loading for Airblast Application Crop Group 10

- 10

(Citrus), Crop Group

11

- 10 (Pome Fruit), Crop Group 13

- 07B (Bushberries, Highbush), Crop Group 14 (Tree Nuts, Except Almonds) 100 37.6 0.219 0.18 lb ai/A 40 acres 0.000251 48 ,0 00 0.0000198 610,000 44,000

Hops 100 37.6 0.219 0.14 lb ai/A 40 acres 0.000196 61 ,0 00 0.0000154 780,000 57,000

Mixing/Loading for Chemigation Soil Directed: Crop

Group 10

- 10 (Citrus), 100 37.6 0.219 0.365 lb ai/A 350 acres 0.00445 2,700 0. 000350 34,000 2,500Page 21 of 32

Table 6.1. 2 . Occupational Handler Non

- Cancer Exposure and Risk Estimates for Flupyradifurone with Label

- Specified PPE (Gloves)

.

Exposure Scenario Crop or Target Level of

Concern Dermal Unit

Exposure (μg/lb ai) 1 Inhalation Unit

Exposure (μg/lb ai) 1 Maximum

Application

Rate 2 Area

Treated or

Amount

Handled Daily 3 Dermal Inhalation Total

Gloves Baseline Dose (mg/kg/day) 4 MOE 5 Dose (mg/kg/day) 6 MOE 7 MOE 8

Application Crop Group 11

- 10

(Pome Fruit), Crop Group 13

- 07B (Bushberries, Highbush), Crop Group 14 (Tree Nuts, Except Almonds)

Broadcast: Field crop, typical 9 100 37.6 0.219 0.18 lb ai/A 350 acres 0.00220 5,500 0.000173 69,000 5,100

Soil Directed: Field Crop Typical 9 100 37.6 0.219 0.365 lb ai/A 350 acres 0.00445 2,700 0.000350 34,000 2,500

Broadcast: Crop Group 15 (Cereal Grains), Cotton, Crop Group 18 (Alfalfa & Forage Crops), Peanuts, Crop Subgroup 1C, Crop Group 6 (Legume Vegetables) 100 37.6 0.219 0.18 lb ai/A 350 acres 0.00220 5,500 0.000173 69,000 5,100

Mixing/Loading for

Groundboom Application Broadcast: Field Crop

Typical 9 100 37.6 0.219 0.18 lb ai/A 80 acres 0.000502 24,000 0.0000394 300,000 22,000

Soil Directed: Field Crop Typical 9 100 37.6 0.219 0.365 lb ai/A 80 acres 0.00102 12,000 0.0000799 150,000 11,000

Broadcast: Crop Group

15 (Cereal Grains), Cotton, Crop Group 18 (Alfalfa & Forage Crops), Peanuts, Crop Subgroup 1C, Crop Group 6 (Legume Vegetables) 100 37.6 0.219 0.18 lb ai/A 200 acres 0.00125 9,600 0.0000985 120,000 8, 900

Applicator

Aerial Application Crop Group 10

- 10

(Citrus), Crop Group

11

- 10 (Pome Fruit), Crop Group 13

- 07B (Bushberries, Highbush), Crop Group 14 (Tree Nuts, 100 2.08 0.0049 0.18 lb ai/A 350 acres 0.000122 98,000 0.00000386 3,100,000 95,000Page 22 of 32

Table 6.1. 2 . Occupational Handler Non

- Cancer Exposure and Risk Estimates for Flupyradifurone with Label

- Specified PPE (Gloves)

.

Exposure Scenario Crop or Target Level of

Concern Dermal Unit

Exposure (μg/lb ai) 1 Inhalation Unit

Exposure (μg/lb ai) 1 Maximum

Application

Rate 2 Area

Treated or

Amount

Handled Daily 3 Dermal Inhalation Total

Gloves Baseline Dose (mg/kg/day) 4 MOE 5 Dose (mg/kg/day) 6 MOE 7 MOE 8

Except Almonds)

Hops 100 2.08 0.0049 0.14 lb ai/A 350 acres 0.0000946 130,000 0.0000030 4,000,000 130,000

Broadcast: Field crop, typical 9 100 2.08 0.0049 0.18 lb ai/A 350 acres 0.000122 98,000 0.00000386 3,100,000 95,000

Crop Group 15 (Cereal Grains), Cotton, Crop Group 18 (Alfalfa & Forage Crops), Peanuts, Crop Subgroup 1C, Crop Group 6 (Legume Vegetables) 100 2.08 0.0049 0.18 lb ai/A 1200 acres 0.000416 29,000 0.0000133 900,000 28,000

Airblast Application Crop Group 10

- 10

(Citrus), Crop Group

11

- 10 (Pome Fruit), Crop Group 13

- 07B (Bushberries, Highbush), Crop Group 14 (Tree Nuts, Except Almonds) 100 1,590 4.71 0.18 lb ai/A 40 acres 0.0106 1,100 0.000424 28,000 1,100

Hops 100 1,590 4.71 0.14 lb ai/A 40 acres 0.00825 1,500 0.00033 36,000 1,400

Groundboom Application Broadcast: Field crop, typical 9 100 16.1 0.34 0.18 lb ai/A 80 acres 0.000215 56,000 0.0000613 200,000 44,000

Soil Directed: Field crop, typical 9 100 16.1 0.34 0.365 lb ai/A 80 acres 0.000436 28,000 0.000124 97,000 22,000

Crop Group 15 (Cereal Grains), Cotton, Crop Group 18 (Alfalfa & Forage Crops), Peanuts, Crop Subgroup 1C, Crop Group 6 (Legume Vegetables) 100 16.1 0.34 0.18 lb ai/A 200 acres 0.000538 22,000 0.000153 78,000 17,000

Flagger

Flagger for Aerial Hops 100 12 0.35 0.14 lb ai/A 350 acres 0.000545 22,000 0.000215 56,000 16,000Page 23 of 32

Table 6.1. 2 . Occupational Handler Non

- Cancer Exposure and Risk Estimates for Flupyradifurone with Label

- Specified PPE (Gloves)

.

Exposure Scenario Crop or Target Level of

Concern Dermal Unit

Exposure (μg/lb ai) 1 Inhalation Unit

Exposure (μg/lb ai) 1 Maximum

Application

Rate 2 Area

Treated or

Amount

Handled Daily 3 Dermal Inhalation Total

Gloves Baseline Dose (mg/kg/day) 4 MOE 5 Dose (mg/kg/day) 6 MOE 7 MOE 8

Application Crop Group 10

- 10

(Citrus), Crop Group

11

- 10 (Pome Fruit), Crop Group 13

- 07B (Bushberries, Highbush), Crop Group 14 (Tree Nuts, Except Almonds)

, Field crop, typical 9

, Crop Group 15 (Cereal Grains), Cotton, Crop Group 18 (Alfalfa & Forage Crops), Peanuts, Crop Subgroup 1C, Crop Group 6 (Legume Vegetables) 100 12 0.35 0.18 lb ai/A 350 acres 0.000701 17,000 0.000276 43,000 12,000

Mixer/loader/Applicator

Backpack Sprayer Ground/Soil Directed:

Crop Group 10

- 10 (Citrus) 100 8,260 2.58 0.0365 lb ai/gal 40 gallons 0.0112 1,100 0.0000471 250,000 1,100

Mechanically Pressurized Handgun Broadcast: Crop Group

10

- 10 (Citrus), Crop Group 11

- 10 (Pome Fruit), Crop Group 13

- 07B (Bushberries, Highbush), Crop Group 14 (Tree Nuts, Except Almonds) 100 1,300 3.9 0.0365 lb ai/gal 1,000 gallons 0. 0132 910 0.00178 6,700 800

Ground/Soil Directed: Crop Group 10

- 10 (Citrus) 100 1,300 3.9 0.0365 lb ai/gal 1,000 gallons 0.0132 910 0.00178 6,700 800

Broadcast: Field crop, typical 9 100 1,300 3.9 0.0365 lb ai/gal 1,000 gallons 0.0132 910 0.00178 6,700 800

Soil Application: Field crop, typical 9 100 1,300 3.9 0.0365 lb ai/gal 1,000 gallons 0.0132 910 0.00178 6,700 800

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” ( May 2013 ); Level of mitigation: Gloves

. *Aerial Application is assessed assuming a closed cockpit (engineering controls).

2 Based on proposed label (Reg. No. SivantoTM (EPA Reg. No. 264

- RRUR ) )

. 3 Exposure Science Advisory Council Policy #9.1.Page 24 of 32

4 Dermal Dose = Dermal Unit Exposure ( μ g/lb ai) × Conversion Factor (0.001 mg/ μ g) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) × DAF ( 7.42 %) ÷ BW ( 80 kg).

5 Dermal MOE = Dermal NOAEL (mg/kg/day) ÷ Der mal Dose (mg/kg/day).

6 Inhalation Dose = Inhalation Unit Exposure ( μ g/lb ai) × Conversion Factor (0.001 mg/ μ g) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) ÷ BW ( 80 kg).

7 Inhalation MOE = Inhalation NOAEL (mg/kg/ day) ÷ Inhalation Dose (mg/kg/day).

8 Total MOE = NOAEL ( 12 mg/kg/day) ÷ ( Dermal Dose + Inhalation Dose )

. 9 Crop Subgroup 1B (except sugarbeet), Crop Group 4 (Leafy Vegetables, except Brassica ), Crop Group 5 ( Brassica Cole Leafy Vegetables), Foliar Application to Crop Group 8

- 10 (Fruiting Vegetables), Foliar Application Crop Group 9 (Cucurbit Vegetables), Crop Group 13

- 07B (Bushberries, lowbush), Crop Subgroup 13

- 07G (Low Growing Berries)

.

Table 6.1.3. Summary of S hort

- and Intermediate

- Term Handler Exposures and Risks for Flupyradifurone Seed Treatment of Soybean

Seeds 1

.

Maximum Application Rate 2 Dermal

Unit Exposure 3 Inhalation

Unit Exposure 3 Amount of

Seed

Treated

or Planted Per Day 4 Dermal

Dose 5 Inhalation Dose 6 Dermal

MOE 7 Inhalation

MOE 8 Combined

MOE 9

lb ai/lb seed mg/lb ai mg/lb ai lb seed/day mg/kg/day mg/kg/day LOC =

100 LOC = 100 LOC =

100
Loader/Applicator

0.00054 0.023 0.00034 281,250 0.00323 0.00000000032 3,700 38,000,000,000 3,700

Sewer

0.00054 0.0062 0.00023 281,250 0.000873 0.000000000016 14,000 770,000,000,000 14,000
Bagger

0.00054 0.0091 0.00016 281,250 0.00128 0.000000000023 9,400 510,000,000,000 9,400

Multiple Activities

0.00054 0.042 0.0016 281,250 0.00591 0.0000000050 2,000 2,400,000,000 2,000

Planters

0.00054 0.25 0.0034 26,667 0.0033 0.000000035 3

, 600 340,000,000 3,600

1 Seed treatment rate calculations are based on the following assumptions: Soybean Seeds : 1, 500 to 3

, 6 00 seeds per lb.

2 Application Rate based on proposed label for flupyradifurone ( EPA Reg. No. 264

- RRUE ).

3 Unit Exposures from HED Exposure Science Advisory Council Policy 14 : Standard Operating Procedures for Seed Treatment (baseline inhalation = no respirator).

4 HED default for lb seed treated/planted per day from HED Exposure Science Advisory Council Interim Policy 15.1 and the BEAD memo “Acres Planted Per Day and Seeding Rates of Crops Grown

in the United States ” (J. Becker, March 2011).

5 Daily Dermal Dose (mg/kg/day) = daily inhalation unit exposure ( m g/ lb ai) × a pplication rate (lb ai/lb seed) × amount planted (lb seed/day) × dermal absorption factor (7.42%) ÷ body weight (8 0 kg adult).

6 Daily Inhalation Dose (mg/kg/day) = daily inhalation unit exposure ( m g/ lb ai) × a ppl ication rate (lb ai/lb seed) × amount planted (lb seed/day) ÷ body weight (8 0 kg adult).

7 Dermal MOE = NOAEL ( 12 mg/kg/day for short

- and intermediate

- term exposure ) ÷ Dermal Dose (mg/kg/day)

. L evel of concern = 100.

8 Inhalation MOE = NOAEL ( 12 mg/kg/day for short

- and intermediate

- term exposure ) ÷ Inhalation Dose (mg/kg/day) . Short

- term level of concern = 100.

9 Total MOE = NOAEL ( 12 mg/kg/day) ÷ ( Dermal Dose + Inhalation Dose )

.Page 25 of 32



## 6

. 2 Occupational Post

- application Exposure/ Risk Estimates

HED uses the term post

- application to describe exposures that occur when individuals are present in an environment that has been previously treated with a pesticide (also referred to as re

entry exposu re). Such exposures may occur when workers enter previously treated areas to perform job functions, including activities related to crop production, such as scouting for pests or harvesting. Post

- application exposure levels vary over time and depend o n s uch things as the type of activity, the nature of the crop or target that was treated, the type of pesticide application, and the chemical’s degradation properties. In addition, the timing of pesticide applications, relative to harvest activities, can gre atly reduce the potential for post

- application exposure.

6

. 2 .1 Occupational Post

- application Inhalation Exposure/Risk Estimates

Based on the Agency's current practices, a quantitative post

- application inhalation exposure assessment was not performed for flupyradifurone at this time primarily because of the low acute inhalation toxicity (Toxicity Category IV), low vapor pressure ( 7.0 x 10

- 9 

## mm Hg at 20 o 

## C ), and the low proposed use rate (0. 365 lb ai/A). However, there are multiple potential sources of pos t

application inhalation exposure to individuals performing post

- application activities in previously treated fields. These potential sources include volatilization of pesticides and resuspension of dusts and/or particulates that contain pesticides. The Agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 6



## . Th e Agency is in the process of evaluating the SAP report as well as available post

- application inhalation exposure data generated by the

ARTF and may, as appropriate, develop policies and procedures, to identify the need for and, subsequently, the way to in corporate occupational post

- application inhalation exposure into the Agency's risk assessments. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational post

- application inhalation exposure assessme nt
for flupyradifurone

.

Although a quantitative occupational post

- application inhalation exposure assessment was not performed, an inhalation exposure assessment was performed for occupational/commercial handlers. Handler exposure resulting from applicat ion of pesticides outdoors is likely to result in higher exposure than post

- application exposure. Therefore, it is expected that these handler inhalation exposure estimates would be protective of most occupational post

- application inhalation exposure scen arios.

Furthermore, inhalation exposure during dusty mechanical activities such as shaking and mechanical harvesting of tree crops is another potential source of post

- application inhalation

exposure. However, the airblast applicator scenario is believed to represent a reasonable worst case surrogate estimate of post

- application inhalation exposure during these dusty mechanical harvesting activities. The non

- cancer inhalation risk estimate for commercial airblast application is not of concern (i.e., MOE > 100)

.

6 

### Available: http://www.epa.gov/scipo ly/SAP/meetings/2009/120109meeting.htmlPage 26 of 32



## A post

- application inhalation exposure assessment is not required as exposure is expected to be negligible. Seed treatment assessments provide quantitative inhalation exposure assessments for seed treaters and secondary handlers (i.e.

, planters). It is expected that these exposure estimates would be protective of most post

- application inhalation exposure scenarios.

6

. 2 .2 Occupational Post

- application Dermal Exposure/Risk Estimates

Occupational Post

- application Dermal Exposure Data and Assumptions A series of assumptions and exposure factors served as the basis for completing the occupational
post

- application risk assessments. Each assumption and factor is detailed below on an individual

basis. A post

- application exposure assessme nt has not been conducted for the proposed soil

directed uses on fruiting vegetables, cucurbits, citrus, and small v ine cl imbing f ruit since the

label indicates that the product is to be applied as a drench to the soil and root zone only

. Currently, HED h as no transfer coefficients or other data to assess post

- application dermal exposures to soil by occupational workers. In general, such exposures are considered to be negligible. Therefore, for the soil

- directed uses, post

- application exposures and risks to occupational workers were not assessed.

Exposure Duration : For flupyradifurone , both short

- and intermediate

- term post

- application exposure could occur for the proposed agricultural uses

. It may be applied throughout the growth season, including pre

- bloom, during bloom, or following bloom, increasing the likelihood of exposure during post

- application activities. However, because the POD is the same

for dermal short

- and intermediate

- term e xposures, one assessment is protective of both

durations.

Transfer Coefficients : It is the policy of HED to use the best available data to assess post

application exposure. Sources of generic post

- application data, used as surrogate data in the

absence of chemical

- specific data, are derived from ARTF exposure monitoring studies, and, as proprietary data, are subject to the data protection provisions of FIFRA. The standard values recommended for use in predicting post

- application exposure that are used in this assessment, known as “transfer coefficients”, are presented in the ExpoSAC Policy 3 7 

## ” which, along with additional information about the ARTF data, can be found at the Agency website 8



## .

Application Rate : A summary of the proposed use pattern of flupyradifurone is shown in Table

4.0.

Exposure Time : The average occupational workday is assumed to be 8 hours.

Dislodgeable Foliar Residues : Chemical

- specific dislodgeable foliar residue data have not been

submitted for flupyradifurone

. Therefore

, this assessment uses HED’s default assumption that 25% of the application is available for transfer on day 0 following the application and the residues dissipate at a rate of 10% each following day.

7 

### Available: http://www.epa.gov/pesticides/science/exposac_policy3.pdf

8 

### Available: http://www.epa.gov/pesticides/science/post

- app

- exposure

- data.htmlPage 27 of 32



## In accordance with 40CFR158, DFR data are required for a ll occupational (e.g., crop, nursery, greenhouse use sites) or residential (e.g., ornamental and vegetable gardens, pick your own farms, retail tree farms) uses that could result in post

- application exposure to foliage. In the

absence of chemical

- specific DFR data, EPA uses default values. The 2012 Standard Operating Procedures for Residential Pesticide Exposure Assessment includes an analysis of a number of DFR studies, which resulted in the selection of a revised default values for the fraction of the

a pplication rate available for transfer after a foliar application (F AR 

## ). These values are based on an analysis of 19 DFR studies. Since that time, the Agricultural Re

- entry Task Force has submitted information (MRID 49299201) that corrects an applicatio n rate error made in the original submission of “ARF039

– Determination of Dermal and Inhalation Exposure to Reentry Workers During Chrysanthemum Pinching in a Greenhouse” (EPA MRID 45344501). As a result, the range of F AR 

## values was revised from 2%

- 89% to 2%

- 47%. In the data, a large range of transferability is observed and this variability can potentially be attributable to many factors such as active ingredient; formulation; field conditions in the studies; weather conditions (e.g., humidity); or m any other difficult to quantify factors. Although witnessed across multiple chemicals, this range in F AR 

## values is not expected when considering DFR data for a single chemical. At this time, the ARTF submission did not alter the selection of 25% as the reasonable, high

- end default value. Because DFR data are not available for flupyradifurone, EPA is using the default value of 25%. Although there may be a small degree of uncertainty in the use of the default DFR value for flupyradifurone (i.e., there is a small chance that the F AR 

## value may exceed the applicable default value ), it is likely that the health

- protective aspects of EPA’s occupational post

- application assessment methodology will more than compensate for this potential uncertainty. For example, when assessing residential and occupational post

application exposure to gardens and ornamentals, EPA a ssumes the following: exposures occur

to zero

- day (i.e., day of application) residues every day of the assessed exposure duration (i.e., EPA assumes that no dissipation or degradation occurs, it doesn’t rain, etc); individuals perform

the same post

- appli cation activities performed in the transfer coefficient study day after day (e.g., weeding, harvesting, pruning, etc.); and individuals engage in these post

- application activities for a high

- end amount of time every day (represented by data reflecting time spent gardening based on survey data).

Given the conservatisms discussed above and the potential compounding nature of these conservatisms, EPA is able to rely upon the calculated exposure estimates with confidence that exposure is not being underestimat ed.

However, since the highest estimated occupational post

- application exposure using default DFR values for flupyradifurone is not minimal in comparison to the level of concern (i.e., the calculated MOE is not greater than 2 times higher than the level of concern, MOE = 170 compared to the LOC of 100); EPA is requiring the 40CFR DFR data. Therefore, EPA is requiring the 40CFR DFR data requirement to facilitate any necessary exposure assessments refinements and to further EPA’s general understanding of t he availability of dislodgeable foliar pesticide residues. The studies should be conducted on three dissimilar crops; however, HED specifically recommends including grapes in the studies.

Occupational Post

- application Non

- Cancer Dermal Exposure and Risk Estimate EquationsPage 28 of 3 2



## The algorithms used to estimate non

- cancer exposure and dose for occupational post

- application workers can be found in Appendix A

.

Occupational Post

- application Non

- Cancer Dermal Risk Estimates The occupational short

- and intermediate

- term dermal post

- application risk estimates ranged

from 170 to 15 ,000 on the day of application. Table 6.2.2 provides a summary of the anticipated

worst

- case post

- application activities and associated transfer coef ficients and MOEs for the proposed crops/use sites.

Table 6

. 2 .2

. Worst

- Case Short

- and Intermediate

- Term Occupational Post

- application Non

- Cancer Exposure and Risk

Estimates for Flupyradifurone

.

Crop/Site Activities Application Rate (lb ai/A) Transfer Coefficient (cm 2 /hr) DFR/TTR 1 Dermal Dose (mg/kg/day) 2 MOE 3

Crop Group 1 B and Crop Group 1C (Beet, Potato, Turnip) Hand Set Irrigation 0.18 1900 0.50 0.0071 1,700

Crop Group 4 (Leafy Vegetables Except

Brassica ) Hand Set Irrigation 0.18 1900 0.50 0.0071 1,700

Crop Group 5 ( Brassica Leafy Vegetables) Scouting, Hand

Harvesting, Hand Weeding 0.18 4200 0.50 0.0157 760

Crop Group 6 (Legume Vegetables) Hand Set Irrigation 0.18 1900 0.50 0.0071 1,700

Crop Group 8

- 10 (Fruiting Vegetables) Hand Set Irrigation 0.18 1900 0.50 0.0071 1,700

Crop Group 9 (Cucurbit Vegetables) Hand Harvesting, Mechanically Assisted Harvesting, Training, Turning, 0.18 550 0.50 0.0021 5,800

Crop Group 10

- 10 ( Citrus ) Hand Harvesting 0.18 1400 0.50 0.0052 2,300

Crop Group 11

- 10 (Pome Fruit) Thinning Fruit 0.18 3600 0.50 0.0135 890

Crop Subgroup 13

- 07B (Bushberries, except cranberry) Hand Harvesting 0.18 1400 0.50 0.0052 2,300

Crop Subgroup 13

- 07G ( Low Growing Berries ) Hand Harvesting 0.18 1100 0.50 0.0041 2,900

Crop Subgroup 13

- 07F (Small Fruit Vine Climbing, E xcept

F uzzy K iwifruit) Girdling/Turning 0.18 19300 0.50 0723 170

Crop Group 14 (Tree
Nuts, E xcept Almonds) Hand Harvesting (Net) 0.18 1400 0.50 0.0052 2,300

Crop Group 15 (Cereal Grains, Except Rice) Detasseling/Hand

Harvesting (Sweet Corn Only) 0.18 8800 0.50 0.0330 360

Hand Set Irrigation 0.18 1900 0.50 0.0071 1,700

Crop Group 18 [Non

Grass Animal Feeds (Forage, Fodder, Straw, Hay)] Hand Set Irrigation 0.18 1900 0.50 0.0071 1,700

Cotton Scouting 0.18 210 0.50 0.00079 15,000Page 29 of 32



### Table 6

. 2 .2

. Worst

- Case Short

- and Intermediate

- Term Occupational Post

- application Non

- Cancer Exposure and Risk

Estimates for Flupyradifurone

.

Crop/Site Activities Application Rate (lb ai/A) Transfer Coefficient (cm 2 /hr) DFR/TTR 1 Dermal Dose (mg/kg/day) 2 MOE 3

Hop Harvesting,

Mechanically

Assisted 0.14 19300 0.39 0.0562 210

Peanut Hand Set Irrigation 0.18 1900 0.50 0.0071 1,700

1 DFR = Application Rate 

### × F 

### × (1

- D) t 

### × 4.54E8 μg/lb 

### × 2.47E

- 8 acre/cm 2 ; where F = 0.25 and D = 0.10 per day

2 Daily Dermal Dose = [DFR (μg/cm 2 ) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × dermal absorption ( 7.42 %)]  BW (kg).

3 MOE = POD ( 12 mg/kg/day) / Daily Dermal Dose.



## Restricted Entry Interval Flupyradifurone is classified as Toxicity Category III and IV based upon data for acute dermal toxicity, acute inhalation toxicity, primary skin irritation, and primary eye irritation. Typically, the REI specified on the proposed label is based on the acute toxicity of the active ingredient. Under 40 CFR 156.20 8 (c) (2) (iii), active ingredients classified as Acute III or IV for acute dermal, eye irritation, and primary skin irrigation are assigned a 12

- hour

REI. However, it is noted that the proposed product label has a 4

- hr REI listed. REIs may be

further re duced from 12 hours if certain criteria are met for both the technical material and the

different end

- use products in accordance with the Pesticide Registration (PR) Notice 95

- 3 [Reduction of Worker Protection Standard (WPS) Interim Restricted Entry Interv als (REIs) for Certain Low Risk Pesticides] 9



## . Based only on the acute toxicity categories, flupyradifurone is a possible candidate for a 4

- hr REI, however, RD should ensure that the additional criteria listed in

PR Notice 95

- 3 are met for the active ingre dient and the end

- use product.

9 

### Available: http://www.epa.gov/PR_Notices/pr95

- 3.ht mlPage 30 of 32



## Appendix A. Summary of Occupational Non

- cancer Algorithms

Occupational Non

- cancer Handler Algorithms

Potential daily exposures for occupational handlers are calculated using the following formulas:

E=UE * AR * A * 0.001 mg/ug

where:

E = e xposure (mg ai/day),

UE = u nit e xposure (μ g ai/ lb ai),

AR = m aximum application rate according to proposed label (lb ai A or lb ai/gal ), and

A = a rea treated or amount handled (e.g., A/day, gal/day)

.

The daily doses are calcula ted using the following formula:

ADD= E * AF

BW

where:

ADD = average daily dose a bsorbed in a given scenario (mg ai/ kg / day),

E = e xposure (mg ai/day),

AF = absorption fa ctor (dermal and/or inhalation), and

BW = body weight (kg)

.

Margin of Exposure: Non

- cancer risk estimates for each application handler scenario are calculated using a Margin of Exposure (MOE), which is a ratio of the toxicological endpoint to the daily dose of concern. The daily dermal and inhalation dose received by occup ational

handlers a re compared to the appropriate POD ( i.e.

, NOAEL) to assess the risk to occupational handlers for each exposure route. All MOE values a re calculated using the following formula:

MOE= POD

ADD

where:

MOE = m argin of e xposure: value used by HED to represent risk estimates (unitless),

POD = p oint of d eparture (mg/kg/day)

, and

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day)

.

Occupational Non

- cancer Post

- application AlgorithmsPage 31 of 32



## Potential daily exposures for occupational post

- application workers are calculated using the following formulas:

DFR t 

## =AR * F* (1

- D) t 

## * ( 4.54E8 ug

lb ) * ( 2.47E

- 8 A

cm 2 

## )

where:

DFR t 

## = dislodgeable foliage residue on day "t" (μg/cm 2 

## ),

AR = a pplication r ate (lb ai/acre),

F = fraction of ai retained on foliage or 25% (unitless),

D = fraction of residue that dissipates daily or 10% (unitless), and

t = number of days after application day (days)

.

E=TC * DFR t 

## * ET * 0.001 mg

ug

where:

E = e xposure (mg ai/day),

TC = t ransfer coefficient (cm 2 

## /hr),

DFR t 

## = d islodgeable f oliar r esidue on day “t” (μg/cm 2 

## ), and

ET = e xposure t ime (hours/day).

The daily doses are calculated using the following formula:

ADD= E * AF

BW

where:

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day),

E = e xposure (mg ai/day),

AF = absorption fa ctor (dermal and/or inhalation), and

BW = body weight (kg).

Margin of Exposure: Non

- cancer risk estimates for each scenario are calculated using a Margin of Exposure (MOE), which is a ratio of the toxicological endpoint to the daily dose of concern. The daily dermal dose received by occupational post

- application workers is compared to the appropriate POD ( i.e.

, NOAEL) to assess the risk to occupational post

- application workers

. All

MOE values a re calculated using the fo llowing formula:

MOE= POD

ADD

where:Page 32 of 32



## MOE = margin of exposure: value used by HED to represent risk estimates (unitless),

POD = point of departure (mg/kg/day), and

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day).