Date: 

Subject: 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

July 31,2014 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

Flupyradifurone. Occupational and Residential Exposure Assessment for a New 

Insecticide Active Ingredient Proposed for Use on Soybean Seeds and the 

Following Agricultural Crops: Brassica; Bushberries, except Cranberry; Cereal 

Grains; Citrus; Cotton; Cucurbits; Fruiting Vegetables; Hops; Leafy Vegetables; 

Legumes; Low Growing Berries; Non-Grass Animal Feeds; Peanuts; Pome Fruit; 

Prickly Pears; Root Vegetables; Small Vine Climbing Fruit; Tree Nuts, except 

Almonds; and Tuberous and Corm Vegetables. 

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 

Assessment 

Case No.: N A 

TXRNo.:NA 

MRIDNo.: NA 

From: 

Through: 

To: 

Kristin 

Risk Assessment 

Rury, Biologist 

Branch 

'fIII9~ ~ Q 

Health Effects Division (7509P) 

CAS No.: 951659-40-8 

40CFR:NA 

Barry O'Keefe, Senior Biologist 

Risk Assessment Branch III 

Health Effects Division (7509P) 

B.o·~ 

and . o 

~~ ? Lv¥.£-_) Cassi Walls, Senior Biologist lC.:ft ,..... : 

Alexandra LaMay, Biologist d 

Exposure Science Advisory Committee (Expo C) I HED 

Jessica Rogala, Risk Manager Reviewer 

Insecticide Branch 

Registration Division (7505P) 

Page I of32 
Introduction 

The Registration Division (RD) requested that the Health Effects Division (HED) conduct an 

occupational and residential exposure and risk assessment for the new insecticide active 

ingredient, flupyradifurone as part of a global joint review. 

It is HED policy to use the best available data to assess exposure. Several sources of generic 

data were used in this assessment as surrogate data in the absence of chemical-specific data, 

including: the Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1 ); the Agricultural 

Handler Exposure Task Force (AHETF) database; the Agricultural Reentry Task Force (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 Agricultural Seed Treatment. 

Some of these data are proprietary, and subject to the data protection provisions of the Federal 

Insecticide, Fungicide, and Rodenticide Act (FIFRA). 

Note: This memorandum was reviewed by the Exposure Science Advisory Committee 

(ExpoSAC) on March 13, 2014. 

Page 2 of32 
Page 3 of 32

Table of Contents

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 Residential 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............................................... 30
Page 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 acetylcholine 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; bushberries, 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 nuts, 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 use 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, 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. 

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 exposure is 

expected for occupational handlers and post-application workers. Chronic exposure is not 

expected for the proposed use patterns. 

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 of 
Page 5 of 32

flupyradifurone toxicity. The database appears to suggest that dogs are more sensitive to the 

effects of flupyradifurone; however, with 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 of 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 study (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 personal 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 handler 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 shortand 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 + 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 

were not of concern. 

Based on the Agency's current 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, which 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 Agricultural 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 Studies Review Board. Descriptions of data sources, as well as 

guidance on their use, can be found at the Agency website1. 

 

1 http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html
Page 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 flupyradifurone 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 + inhalation) 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 were 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 100); therefore, 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 Characterization

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 acute 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 LD50 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 LD50 > 2000 mg/kg III

870.1300 Acute Inhalation - Rat 48844105 LC50 > 4671 mg/m3 (4.67 mg/L) IV
Page 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 Points of Departure (PODs) 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 

appears 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 decrease 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. Summary of Toxicological Doses and Endpoints for use in Flupyradifurone Occupational Human Health Risk 

Assessments.

Exposure 

Scenario

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 

intermediateterms (1-6 

months)

NOAEL = 12 mg/kg/day

7.42% dermal 

absorption factor

UFA= 10x

UFH=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 

intermediateNOAEL = 12 mg/kg/day

UFA= 10x

UFH=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 
Page 8 of 32

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

Assessments.

Exposure 

Scenario

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

Offspring 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. No 

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. UFA = extrapolation from 

animal to human (interspecies). UFH = 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, toxicity 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 assessment 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 – NonGrass 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/A
Page 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 seed
Page 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., groundboom 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 Registration 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 20oC), 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, 20103. The Agency is in the process of 

evaluating 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 developed, 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 task. Job requirements 

 

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

3 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
Page 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 occupational 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; 

 Flagging for aerial applications; 

 Mixing/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).

Occupational 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-specific 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 Table4”, which, along with 

additional information on HED policy on use of surrogate data, including descriptions of the 

various sources, can be found at the Agency website5. 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 SOP 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.html
Page 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 typical field crops;

 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 applicators 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 proposed 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 

intermediate-term duration used in HED’s occupational assessments, HED has no information to 

indicate 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 sleeved 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 requires 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 occupational 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 risk 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 addition 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 quantitative 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 guidance 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 are 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 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inhalation Total

Baseline Baseline Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE8

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, typical9 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 34,000 450
Page 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 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inhalation Total

Baseline Baseline Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE8

Broadcast: Field crop, 

typical9 100 220 0.219 0.18 lb ai/A 350 acres 0.0129 930 0.000173 69,000 920

Soil Directed: Field 

Crop Typical9 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 

Typical9 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 Typical9 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, 

typical9 100 2.08 0.0049 0.18 lb ai/A 350 acres 0.000122 98,000 0.00000386 3,100,000 95,000
Page 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 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inhalation Total

Baseline Baseline Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE8

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, 

typical9 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, typical9 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 17,000
Page 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 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inhalation Total

Baseline Baseline Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE8

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, typical9, 

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 0.000276 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, 

typical9 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, typical9 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 (μg/lb ai) × Conversion Factor (0.001 mg/μg) × 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 (μg/lb ai) × Conversion Factor (0.001 mg/μg) × 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 6.1.2. 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 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inhalation Total

Gloves Baseline Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE8

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, typical9 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 48,000 0.0000198 610,000 44,000

Hops 100 37.6 0.219 0.14 lb ai/A 40 acres 0.000196 61,000 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 2,500
Page 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 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inhalation Total

Gloves Baseline Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE8

Application Crop Group 11-10 

(Pome Fruit), Crop 

Group 13-07B 

(Bushberries, 

Highbush), Crop 

Group 14 (Tree Nuts, 

Except Almonds)

Broadcast: Field crop, 

typical9 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 Typical9 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 

Typical9 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 Typical9 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 95,000
Page 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 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inhalation Total

Gloves Baseline Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE8

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, 

typical9 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, 

typical9 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, typical9 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 16,000
Page 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 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inhalation Total

Gloves Baseline Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE8

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, typical9, 

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, 

typical9 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, typical9 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 (μg/lb ai) × Conversion Factor (0.001 mg/μg) × 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 (μg/lb ai) × Conversion Factor (0.001 mg/μg) × 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 Short- and Intermediate-Term Handler Exposures and Risks for Flupyradifurone Seed Treatment of Soybean 

Seeds1.

Maximum 

Application Rate2

Dermal

Unit Exposure3

Inhalation

Unit 

Exposure3

Amount of 

Seed 

Treated

or Planted 

Per Day4

Dermal 

Dose5

Inhalation Dose6 Dermal 

MOE7

Inhalation 

MOE8

Combined 

MOE9

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 3,600 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 (mg/lb ai) × application rate (lb ai/lb seed) × amount planted (lb seed/day) × dermal absorption factor (7.42%) ÷ body weight (80 kg 

adult).

6 Daily Inhalation Dose (mg/kg/day) = daily inhalation unit exposure (mg/lb ai) × application rate (lb ai/lb seed) × amount planted (lb seed/day) ÷ body weight (80 kg adult).

7 Dermal MOE = NOAEL (12 mg/kg/day for short- and intermediate-term exposure) ÷ Dermal Dose (mg/kg/day). Level 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 reentry exposure). 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 on such 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 greatly 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 20oC), and 

the low proposed use rate (0.365 lb ai/A). However, there are multiple potential sources of postapplication 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, 20106. The 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 incorporate 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 assessment 

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 application 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 scenarios.

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/scipoly/SAP/meetings/2009/120109meeting.html
Page 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 assessment has not been conducted for the proposed soildirected uses on fruiting vegetables, cucurbits, citrus, and small vine climbing fruit since the 

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

Currently, HED has 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 exposures, one assessment is protective of both 

durations. 

Transfer Coefficients: It is the policy of HED to use the best available data to assess postapplication 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 37” which, along with 

additional information about the ARTF data, can be found at the Agency website8. 

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.html
Page 27 of 32

In accordance with 40CFR158, DFR data are required for all 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 

application rate available for transfer after a foliar application (FAR). 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 application 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 FAR 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 many other difficult to quantify factors. Although witnessed across multiple 

chemicals, this range in FAR 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 FAR

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 postapplication exposure to gardens and ornamentals, EPA assumes 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-application 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 underestimated. 

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 the 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 Equations
Page 28 of 32

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 coefficients 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 

(cm2/hr) DFR/TTR1 Dermal Dose (mg/kg/day)2 MOE3

Crop Group 1B 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, Except 

Fuzzy Kiwifruit)

Girdling/Turning 0.18 19300 0.50 0723 170

Crop Group 14 (Tree 

Nuts, Except 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 [NonGrass 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 15,000
Page 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 

(cm2/hr) DFR/TTR1 Dermal Dose (mg/kg/day)2 MOE3

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/cm2; where F = 0.25 and D = 0.10 per day 

2 Daily Dermal Dose = [DFR (μg/cm2) × 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 156.208 (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 reduced 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 Intervals (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 ingredient and the end-use product.

 

9 Available: http://www.epa.gov/PR_Notices/pr95-3.html
Page 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 = exposure (mg ai/day),

UE = unit exposure (μg ai/lb ai),

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

A = area treated or amount handled (e.g., A/day, gal/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 = exposure (mg ai/day),

AF = absorption factor (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 occupational 

handlers are compared to the appropriate POD (i.e., NOAEL) to assess the risk to occupational 

handlers for each exposure route. All MOE values are calculated using the following formula:

MOE= 

POD

ADD

where:

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).

Occupational Non-cancer Post-application Algorithms
Page 31 of 32

Potential daily exposures for occupational post-application workers are calculated using the 

following formulas:

DFRt=AR * F* (1-D)t* (4.54E8

ug

lb) * (2.47E-8

A

cm2

)

where:

DFRt = dislodgeable foliage residue on day "t" (μg/cm2),

AR = application rate (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 = exposure (mg ai/day),

TC = transfer coefficient (cm2/hr),

DFRt = dislodgeable foliar residue on day “t” (μg/cm2), and

ET = exposure time (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 = exposure (mg ai/day),

AF = absorption factor (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 are calculated using the following 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).