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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION

Date: May 30, 2014

Subject: Fluopyram. Occupational and Residential Exposure Assessment for New Use as 

a Soil/In-Furrow Treatment for Cotton and Peanut, and as a Seed Treatment to 

Cotton and Soybean.

PC Code: 080302 DP Barcode: D419530

Decision No.: 481199 Registration No.: 264-1078,264-

RRAT

Petition No.: NA Regulatory Action: Section 3

Risk Assessment Type: Occupational/Residential Exposure Assessment Case No.: NA

TXR No.: NA CAS No.: 658066-35-4

MRID No.: NA 40 CFR: §180.661

From: Barry O’Keefe, Senior Biologist

Risk Assessment Branch III

Health Effects Division (7509P)

Through: Christine Olinger, Branch Chief

Risk Assessment Branch III

Health Effects Division (7509P)

and

Kelly O’Rourke, ExpoSAC Reviewer

Jennifer Tyler, ExpoSAC Reviewer

Exposure Science Advisory Committee (ExpoSAC) / HED

To: Barry O’Keefe, Risk Assessor

Risk Assessment Branch III

Health Effects Division (7509P)

Introduction

The Health Effects Division (HED) of the Office of Pesticide Programs (OPP) is charged with 

estimating the risk to human health from exposure to pesticides. The Registration Division (RD) 

of OPP has requested that HED evaluate the hazard and exposure data and conduct occupational 

and residential exposure assessments, as needed, to estimate the risk to human health that will 
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result from the proposed uses of fluopyram. This memorandum serves as HED’s assessment of 

the occupational and residential exposure and risk from these proposed uses. 

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

Handler Exposure Task Force (AHETF) database; ExpoSAC Policy 14, 15, and 15.1 (SOPs for 

Seed Treatment), The Reviewer’s Aid to Calculating Occupational Exposure from Activities 

Related to Agricultural Seed Treatment, and the Agricultural Reentry Task Force (ARTF) 

database. 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 May 15, 2014. 
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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

2.3 Label Recommendations.................................................................................................. 7

3.0 Hazard Characterization....................................................................................................... 7

4.0 Use Profile ........................................................................................................................... 9

5.0 Residential Exposure and Risk Estimates.......................................................................... 10

6.0 Occupational Exposure and Risk Estimates ...................................................................... 11

6.1 Occupational Handler Exposure/Risk Estimates............................................................ 11

6.2 Occupational Post-application Exposure/Risk Estimates .............................................. 18

6.2.1 Occupational Post-application Inhalation Exposure/Risk Estimates...................... 18

6.2.2 Occupational Post-application Dermal Exposure/Risk Estimates.......................... 19

Appendix A. Summary of Occupational and Residential Non-cancer Algorithms..................... 22
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1.0 Executive Summary

The active ingredient, fluopyram (N-[2-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]ethyl]-2-

(trifluoromethyl)benzamide) is a pyridylethylamide SDH (succinate-dehydrogenase-inhibitor, 

complex II) fungicide with broad spectrum of activity against fungal diseases in a wide range of 

crops. 

Use Profile

The registrant, Bayer CropScience is requesting new uses of fluopyram as a soil/in-furrow 

treatment for cotton and peanut, and as a seed treatment to cotton and soybean. The at-planting 

soil/in-furrow treatment for cotton and peanut is an amendment to the Luna® Privilege label 

(EPA Reg. No. 264-1078). Additionally, post-emergent application to peanut by overhead 

chemigation is proposed on the Luna® Privilege label. The proposed Luna® Privilege label 

requires occupational handlers to wear the following personal protective equipment (PPE): long 

sleeved shirts, long pants, shoes, socks, and chemical resistant gloves. The proposed restricted 

entry interval (REI) is 12 hours.

The seed treatment to cotton and soybean is on the new end-use product Fluopyram ST (EPA 

Reg. No. 264-RRAT). The proposed Fluopyram ST label requires occupational handlers to wear 

the following PPE: long-sleeved shirt, long pants, shoes plus socks, and waterproof gloves.

Both products (Luna® Privilege and Fluopyram ST) are liquid formulations containing 41.5% ai 

(4.16 lb ai /gal) and 48.4% ai (5 lb ai/gal), respectively. 

Fluopyram is currently registered on a variety of agricultural food crops, including apple, cherry 

(sweet and tart), dried beans, peanut, potato, strawberry, sugar beets, tree nuts, watermelon, and 

viniferous variety grapes. There are no existing or proposed residential uses of fluopyram.

Exposure Profile

There is a potential for short- and intermediate-term occupational dermal and inhalation exposure 

to fluopyram during handling tasks (mixing, loading, and application) and during postapplication activities. Long-term occupational exposure is not expected for the proposed use 

patterns associated with fluopyram. 

Hazard Concerns

Short- and intermediate term dermal risks are based on increased cholesterol in females, increased 

prothrombin time in males, increased liver weight (both sexes) and liver hypertrophy effects observed 

at the Lowest Observed Adverse Effect Level (LOAEL) of 1000 mg/kg/day (No Observed Adverse 

Effect Level (NOAEL) of 300 mg/kg/day) from a 28-day dermal toxicity study in rats. Short- and 

intermediate-term inhalation risks are based on decreased pup body weight and body weight gain, and 

decrease in spleen and thymus weight effects observed at the LOAEL of 82.8 mg/kg/day (NOAEL of 

14.5 mg/kg/day) from a 2-generation reproduction study in rats. The subchronic inhalation study data 

requirement was waived by the Hazard and Science Policy Council (HASPOC) (K. Rury, 1/30/13, 

TXR No. 0056523). Since the dermal and inhalation endpoints are not based on developmental 

effects, the average body weight of an adult (80 kg) was used in the exposure assessments. Further, 
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since the toxicological effects for dermal and inhalation routes are not similar, the risks from both 

routes are not combined together.

Fluopyram has low acute toxicity by the oral and dermal routes of exposure (Toxicity Category 

III) and also by the inhalation route of exposure (Toxicity Category IV). It is not a dermal or eye 

irritant and is not a dermal sensitizer.

The cancer classification is “not likely to be carcinogenic to humans.” There is no mutagenic 

concern for fluopyram. 

Occupational Exposure

No chemical-specific handler exposure data were submitted in support of these Section 3

registrations. To assess handler exposures for regulatory actions when chemical-specific 

monitoring data are not available, HED relied on the most scientifically-reliable surrogate data 

currently available from various sources such as the PHED, and the AHETF. Some of this data, 

such as the industry task force data, is compensatory, subject to the data protection provisions of 

FIFRA. For the in-furrow uses on cotton and peanut, non-cancer risk estimates for dermal (with 

gloves) and inhalation (no respirator) short- and intermediate-term occupational handler 

exposures all resulted in MOE ≥100, and therefore, do not exceed HED’s level of concern, with 

MOEs ranging from 8,200 to 84,000 for dermal exposures with gloves and from 68,000 to 

300,000 for inhalation exposures. For the seed treatment uses on soybean and cotton seeds, noncancer risk estimates for dermal and inhalation short-term occupational handler exposures all 

resulted in MOE ≥100, and therefore, do not exceed HED’s level of concern, with MOEs ranging 

from 480 to 7,300 for dermal exposures and from 620 to 26,000 for inhalation exposures.

Short- and intermediate-term dermal post-application exposures and risks to occupational 

workers were estimated using standard values established by HED since no chemical-specific 

data were submitted. The transfer coefficients (TC) used for all post-application activities were 

the TCs established by ExpoSAC in the revised SOP No. 3.1. The dislodgeable foliar residue 

(DFR) levels for agricultural crops were estimated using HED standard values where it is 

assumed that the initial residue on treated foliage is 25% of the application rate and the residues 

degrade at a rate of 10% per day. The occupational post-application non-cancer MOEs do not 

exceed HED’s level of concern (MOEs ≥100), with dermal MOEs ranging from 2,600 to 69,000.

Based on the Agency's current practices, a quantitative non-cancer occupational post-application 

inhalation exposure assessment was not performed for fluopyram 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 fluopyram.

Restricted Entry Interval: When post-application risk estimates are not a concern on day 0 (12 

hours following application), the REI is based on the acute toxicity of fluopyram technical 

material. Fluopyram is classified as Toxicity Category III by the acute dermal route of exposure, 

and Toxicity Category IV for acute eye irritation potential and skin irritation potential. Under 

the WPS for Agricultural Pesticides, active ingredients classified as acute toxicity categories III 

or IV for these routes are assigned a 12-hour REI. Therefore, the 12-hour REI that appears on 

the proposed labels would be adequate. 
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Residential Exposure

Based on product labels, the products are not intended for use by homeowners, or by 

occupational handlers in residential settings. Additionally, there are no existing uses in 

residential settings. Therefore, non-occupational/residential risk assessments have not been 

completed.

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 AHETF database; the ARTF database; and ExpoSAC Policies 14, 15, and 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. 

2.0 Risk Assessment Conclusions and Recommendations

2.1 Summary of Risk Estimates

There are no occupational risk estimates of concern associated with the proposed uses of 

fluopyram. 

2.2 Data Deficiencies and Requirements

There are no data deficiencies or requirements missing from the fluopyram database at this time.

Turf Transferable Residue (TTR): A TTR study is not required for fluopyram at this time, since 

there is no proposed or registered use on turf. 

Dislodgeable Foliar Residue (DFR): A DFR study is not required for fluopyram at this time.

In accordance with 40 CFR158, 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 

 

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

http://www.epa.gov/pesticides/science/post-app-exposure-data.html
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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 fluopyram, 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 fluopyram (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. 

Since the highest estimated occupational post-application exposure using default DFR values for 

fluopyram is minimal in comparison to the level of concern (i.e., the calculated MOE is greater 

than 2 times higher than the level of concern, MOE = 2,600 compared to the LOC of 100); EPA 

is waiving the 40 CFR DFR data requirement. In this instance, it is unlikely that chemicalspecific DFR data would be needed to further refine exposure assessments or would add 

appreciably to our overall understanding of the availability of dislodgeable foliar pesticide 

residues for fluopyram. 

2.3 Label Recommendations

There are no label recommendations associated with these actions. 

3.0 Hazard Characterization

Acute Toxicity

The acute toxicity for fluopyram is summarized in Table 3.1. Fluopyram has low acute toxicity 

by the oral and dermal routes of exposure (Toxicity Category III) and by the inhalation route of 

exposure (Toxicity Category IV). It is not a dermal or eye irritant and is not a dermal sensitizer.
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TABLE 3.1. Acute Toxicity Profile of Fluopyram Technical.

Guideline No. Study Type MRID(s) Results Toxicity 

Category

870.1100 Acute Oral 47372430

LD50 > 2000 mg/kg in 

females III

870.1200 Acute Dermal 47372432

LD50 > 2000 mg/kg in males 

&, females III

870.1300 Acute Inhalation (4 hr) 47372434

LC50 > 5.112 mg/L in males 

& females IV

870.2400 Primary Eye Irritation 47372436

No positive scores at 24 hr; 

not irritating IV

870.2500 Primary Skin Irritation 47723701 Not irritating IV

870.2600 Dermal Sensitization 47372440 Not sensitizing N/A

870.2600 Dermal Sensitization 47753403 Not sensitizing N/A

Toxicological PODs Used for Risk Assessment

Short- and intermediate term dermal risks are based on increased cholesterol in females, 

increased prothrombin time in males, increased liver weight (both sexes) and liver hypertrophy

effects observed at the LOAEL of 1000 mg/kg/day (NOAEL of 300 mg/kg/day) from a 28-day 

dermal toxicity study in rats. Short- and intermediate-term inhalation risks are based on 

decreased pup body weight and body weight gain, and decrease in spleen and thymus weight

effects observed at the LOAEL of 82.8 mg/kg/day (NOAEL of 14.5 mg/kg/day) from a 2-

generation reproduction study in rats. The subchronic inhalation study data requirement was 

waived by the Hazard and Science Policy Council (HASPOC) (K. Rury, 1/30/13, TXR No. 

0056523). 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. Since the 

dermal and inhalation endpoints are not based on developmental effects, the average body weight 

of an adult (80 kg) was used in the exposure assessments. Further, since the toxicological effects 

for dermal and inhalation routes are not similar, the risk estimates from both routes are not 

combined together.

There is no mutagenic concern for fluopyram. The CARC classified fluopyram as “Not Likely 

to be Carcinogenic to Humans” at doses that do not induce cellular proliferation in the liver 

or thyroid glands. This classification was based on convincing evidence that non-genotoxic 

modes of action for liver tumors in rats and thyroid tumors in mice have been established and 

that the carcinogenic effects have been demonstrated as a result of a mode of action dependent 

on activation of the CAR/PXR receptors. The CARC has determined that quantification of risk 

is not required.
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A summary of the toxicological doses and endpoints for occupational human health risk 

assessment is provided in Table 3.2. 

Table 3.2. Summary of Toxicological Doses and Endpoints for Fluopyram for Use in Occupational Human 

Health Risk Assessments.

Exposure/

Scenario

Point of 

Departure

Uncertainty 

Factors

Level of Concern 

for Risk 

Assessment

Study and Toxicological Effects

Short- (1-30 

days) & 

IntermediateTerm Dermal (1-

6 months)

NOAEL = 

300 

mg/kg/day

UFA = 10x 

UFH = 10x 

LOC = 

MOE ≤ 100

28-day dermal toxicity study in the rat

LOAEL of 1000 mg/kg/day based on 

increased cholesterol in females, 

increased prothrombin time in males, 

increased liver weight (both sexes) and 

liver hypertrophy.

(low dermal absorption, <1%)

Short- (1-30 

days) & 

IntermediateTerm (1-6 

months) 

Inhalation

NOAEL = 

14.5 

mg/kg/day

UFA = 10x 

UFH = 10x 

LOC = 

MOE ≤ 100

2-generation reproduction study in rats

LOAEL = 82.8 mg/kg/day based on 

decreased pup body weight and body 

weight gain and decrease in spleen and 

thymus weight. 

Cancer (oral, 

dermal, 

inhalation)

Classification: The CARC classified fluopyram as “Not Likely to be Carcinogenic to Humans” 

at doses that do not induce cellular proliferation in the liver or thyroid glands.

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). MOE = margin of exposure. LOC = level of concern.

4.0 Use Profile 

The registrant, Bayer CropScience is requesting new uses of fluopyram as a soil/in-furrow 

treatment for cotton and peanut, and as a seed treatment to cotton and soybean. The at-planting 

soil/in-furrow treatment for cotton and peanut is an amendment to the Luna Privilege label (EPA 

Reg. No. 264-1078). Additionally, post-emergent application to peanut by overhead 

chemigation is proposed on the Luna® Privilege label. The proposed Luna® Privilege label 

requires occupational handlers to wear the following PPE: long sleeved shirts, long pants, shoes, 

socks, and chemical resistant gloves. The proposed REI is 12 hours.

The seed treatment to cotton and soybean is on the new end-use product Fluopyram ST (EPA 

Reg. No. 264-RRAT). The proposed Fluopyram ST label requires occupational handlers to wear 

the following PPE: long-sleeved shirt, long pants, shoes plus socks, and waterproof gloves.

Both products are liquid formulations containing 41.5% ai (4.16 lb ai /gal) and 48.4% ai (5 lb 

ai/gal), respectively. The uses and application rates are described in Table 4.1.
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Table 4.1. Summary of Proposed Directions for Use of Fluopyram.

Application

Timing, Type, 

and Equip.

Formulation

[EPA Reg. 

No.]

Application

Rate 

(lb ai/A)

Max. No. 

Applic. 

per 

Season

Max. 

Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

Cotton

Seed treatment 

with commercial 

slurry mixture 

equipment only

Fluopyram ST

(5 lb ai/gal)

[264-RRAT]

0.003472a

lb ai/lb seed

0.35 mg ai/seed

(1.97 fl oz

per 100,000

cotton seeds)

1

0.45 (from 

all uses) NA

Do not use treated 

seed for food, feed, 

or oil purposes.

In-furrow during 

planting.

Luna Privilege

(4.16 lb ai/gal)

[264-1078]

0.22

(6.84 fl oz/A) 1 NS NA

Direct application 

into the furrow and 

cover with soil.

Soybean

Seed treatment 

with commercial 

slurry mixture 

equipment

Fluopyram ST

(5 lb ai/gal)

[264-RRAT]

0.001983a

lb ai/lb seed

0.25 mg ai/seed

(1.97 fl oz

per 140,000

soybean seeds)

1

0.45 (from 

all uses) NA

Do not use treated 

seed for food, feed, 

or oil purposes.

Do not graze or feed 

soybean forage and 

hay to livestock.

Peanut

In-furrow during 

planting or by 

chemigation 

post-emergent.

Luna Privilege

(4.16 lb ai/gal)

[264-1078]

0.22

(6.84 fl oz/A) 1 0.45 NA

Direct application 

into the furrow and 

cover with soil.

a Based on seed counts (4,500 cotton seeds maximum/lb and 3,600 soybean seeds maximum/lb) from BEAD memo: 

“Acres Planted Per Day and Seeding Rates of Crops Grown in the United States.”.

5.0 Residential Exposure and Risk Estimates

Based on product labels, the products are not intended for use by homeowners, or by 

occupational handlers in residential settings. Therefore, non-occupational/residential risk 

assessments have not been completed.

Spray Drift

Spray drift is always a potential source of exposure to residents nearby to spraying operations. 

This is particularly the case with aerial application, but to a lesser extent, could also be a 

potential source of exposure from the airblast and groundboom application methods additionally 

employed for fluopyram. The Agency has been working with the Spray Drift Task Force, EPA 

Regional Offices, and State Lead Agencies for pesticide regulation and other parties to develop 

the best spray drift management practices. The Agency is now requiring interim mitigation 

measures for aerial applications that must be placed on product labels/labeling. The Agency has 

completed its evaluation of the new database submitted by the Spray Drift Task Force, a 

membership of U.S. pesticide registrants, and is developing a policy on how to appropriately 

apply the data and the AgDRIFT computer model to its risk assessments for pesticides applied 

by air, orchard airblast, and ground hydraulic methods. After the policy is in place, the Agency 
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may impose further refinements in spray drift management practices to reduce off-target drift 

and risks associated with aerial as well as other application types where appropriate.

Residential Bystander Post-Application Inhalation Exposure

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 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The 

agency has evaluated the SAP report and has developed a Volatilization Screening Tool and a 

subsequent Volatilization Screening Analysis 

(http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219). During Registration 

Review, the agency will utilize this analysis to determine if data (i.e., flux studies, route-specific 

inhalation toxicological studies) or further analysis is required for fluopyram.

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 

(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. 

In-Furrow Use on Cotton & Peanut, and Post-Emergent Chemigation to Peanuts

Based on the anticipated use patterns and current labeling, types of equipment and techniques 

that can potentially be used, occupational handler dermal and inhalation exposures are expected 

from the proposed uses of fluopyram. The quantitative dermal and inhalation exposure/risk 

assessment developed for occupational handlers is based on the following scenarios: 

1) Mixing/loading liquids for chemigation,

2) Mixing/loading liquids for groundboom application, and

3) Applying sprays via groundboom equipment.

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 maximum application rates for each crop or use site are 

provided in Table 4.1.

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, 
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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 Table2”, 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 website3.

Area Treated or Amount Handled: The daily areas treated or amounts handled were defined for 

each handler scenario (in appropriate units) by determining the amount that can be reasonably 

treated by an individual in a single day. When possible, the assumptions for daily areas treated 

or amounts handled are taken from the HED’s ExpoSAC Policy 9.1: “Standard Values for Daily 

Acres Treated in Agriculture”. Values used for area treated or amount handled include the 

following:

1) 350 acres for mixing/loading for chemigation applications to typical field crops

(peanuts),

2) 80 acres for groundboom applications to typical field crops (e.g. peanuts), and

3) 200 acres for groundboom applications to high acreage field crops (i.e. cotton).

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 fluopyram, based on the existing labeled use patterns, short- and intermediate-term 

exposures are expected. Long-term exposure is therefore not expected.

Mitigation/Personal Protective Equipment: Occupational handler exposure assessments are 

completed by HED using different levels of risk mitigation. Typically, HED uses a tiered 

approach. The lowest tier is designed as the baseline exposure scenario (i.e., long-sleeve shirt, 

long pants, shoes, socks, no respirator). If risk estimates are of concern at baseline attire, then 

increasing levels of PPE (i.e., gloves, respirators) are evaluated. This approach is used to ensure 

that the lowest level of risk mitigation that provides adequate protection is selected. Estimates of 

dermal and inhalation exposure were calculated 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. The fluopyram product label direct mixers, loaders, applicators and other handlers 

to wear long-sleeved shirt and long pants, and chemical resistant gloves.

Occupational Handler Non-Cancer Exposure and Risk Estimate Equations

 

2 Available: http://www.epa.gov/opp00001/science/handler-exposure-table.pdf

3 Available: http://www.epa.gov/pesticides/science/handler-exposure-data.html
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The algorithms used to estimate non-cancer exposure and dose for occupational handlers can be 

found in Appendix A.

Summary of Occupational Handler Non-Cancer Exposure and Risk Estimates

For all exposure scenarios the risk estimates do not exceed HED’s LOC (MOEs ≥100) at 

baseline PPE (i.e. without gloves or a respirator). The MOEs ranged from 1,400 (for dermal 

exposure) to 300,000 (for inhalation exposure). See Table 6.1.1 for the summary of occupational 

handler risk estimates.
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Table 6.1.1. Non-Cancer Occupational Short- and Intermediate-Term Dermal and Inhalation Exposures and Risk Estimates For Fluopyram

Exposure Scenario Crop or 

Target

Application

Ratea

(lb ai/A)

Area 

Treated 

Dailyb

(A/day) 

Unit Exposured Daily Exposuree(mg/kg/day) MOEf

Baseline 

Dermalc

(mg/lb ai)

PPE-G 

Dermalc

(mg/lb ai)

Baseline 

Inhalationc

(μg/lb ai)

Baseline 

Dermal

PPE-G 

Dermal

Baseline 

Inhalation

Baseline 

Dermal

PPE-G 

Dermal

Baseline 

Inhalation

Mixer/Loader

Mixing/Loading Liquid 

Concentrates for 

Chemigation Applications

Peanut 0.22 350 0.22 0.0376 0.219 0.214 0.0366 0.000213 1,400 8,200 68,000

Mixing/Loading Liquids 

Concentrates for 

Groundboom Applications

Peanut 0.22 80 0.22 0.0376 0.219 0.0489 0.00836 0.0000486 6,100 36,000 300,000

Cotton 0.22 200 0.22 0.0376 0.219 0.122 0.0209 0.000122 2,500 14,000 120,000

Applicator

Applying Sprays via 

Groundboom Equipment

Peanut 0.22 80 0.0786 0.0161 0.34 0.0175 0.00358 0.0000756 17,000 84,000 190,000

Cotton 0.22 200 0.0786 0.0161 0.34 0.0436 0.00895 0.000189 6,900 34,000 77,000

a. Application Rates are based on proposed uses from the fluopyram label (Luna® Priviledge).

b. Science Advisory Council Policy No. 9.1.

c. Baseline Dermal: Long-sleeve shirt, long pants, and no gloves. PPE-G Dermal: Baseline plus chemical-resistant gloves. Baseline Inhalation: no respirator.

d. Unit Exposures are based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (May 2013). 

e. Daily Exposure (mg/kg/day) = Application Rate (lb ai/A) * Unit Exposure (mg/lb ai) * Area Treated or Amount Applied (acre/day) / 80 kg.

f. MOE = NOAEL (mg/kg/day) / Daily Exposure (mg/kg/day); where dermal NOAEL = 300 mg/kg/day and inhalation NOAEL = 14.5 mg/kg/day.
Page 15 of 22

Seed Treatment Use on Cotton & Soybean Seeds

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 seed 

treatment use. The quantitative exposure/risk assessment developed for occupational handlers is 

based on the following scenarios: 

1. Mixing/loading liquids for commercial seed treatment,

2. Bagging treated seed,

3. Sewing bags,

4. Multiple activities, and

5. Planting treated seed.

Occupational seed treatment handlers may experience short- and intermediate-term exposure to

fluopyram while performing seed treatment activities in commercial settings. In addition, 

occupational secondary handlers may experience short- and intermediate-term exposure while 

planting fluopyram-treated seeds. No chemical-specific handler exposure data were submitted in 

support of this use pattern. For assessing commercial seed treatment and seed planting activities, 

unit exposure data were taken from HED ExpoSAC Policy 14: SOPs for Seed Treatment. The 

amount of ai handled depends on the application rate (lb ai/lb seed) and the pounds of seed 

treated in a day (or the pounds of seed that can be planted in a day), all of which vary depending 

upon the seed type. Values for the amount of seed treated and planted per day were obtained 

from HED ExpoSAC Policy 15 and 15.1.

Treating Seed (Primary Handler)

Potential occupational exposure scenarios from the use of fluopyram as a commercial seed 

treatment include: mixing, loading, applying liquid formulations; bagging treated seed; sewing 

bags; and multiple activities. Typically, for large-scale commercial seed treatments, workers 

perform only those specific individual tasks listed above; however, it is assumed that workers 

also may perform multiple activities throughout the day. As a result a “multiple activities” 

scenario (i.e. where one worker performs all seed treatment tasks such as loading/applying, 

sewing, bagging, cleaning, calibration, repair, forklift driver, etc.) was addressed.

Planting Treated Seed (Secondary Handler)

Potential occupational exposure scenarios from the use of fluopyram as a commercial seed 

treatment include planting treated seed (secondary handler). Planting treated seed consists of the 

farmer purchasing bags of treated seed, placing the seed in the hopper and applying seed to fields 

(considered a secondary handler exposure scenario).

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: 

Refer to the proposed use pattern table in Section 4.0.
Page 16 of 22

Unit Exposures: It is the policy of HED to use the best available data to assess handler exposure. 

Chemical-specific data for assessing exposure during commercial seed treatment and seed 

planting were not submitted to the Agency in support of these applications. Unit exposures are 

from ExpoSAC Policy 14: SOPs for Seed Treatment (May 1, 2003) and are based on data for 

open mixing/loading/application systems.

Amount Handled: 

HED is currently in the process of revising ExpoSAC Policy 15: Amount of Seed Treated or 

Planted per Day (March 2, 2004) in efforts to update the daily amount of seed treated in 

commercial seed treatment facilities. With the increasing demand for hybridized treated seeds, 

there have been modifications not only in the seed treatment equipment, but in the market shares 

of new and currently registered pesticide products. HED understands that due to the high cost of 

producing hybrid seeds, direct seeding is done in a precision manner which requires lower 

volumes of seed per acre. However, this does not provide a direct correlation to the amount of 

seed which is treated in the commercial seed treatment facilities. 

The amount of seed handled (for both primary/treater and secondary/planter handlers) is based 

on HED ExpoSAC Policy 15, HED ExpoSAC Policy SOP 15.1, and the BEAD memo: “Acres 

Planted Per Day and Seeding Rates of Crops Grown in the United States.”

The amount of seed treated per day at a commercial facility for short-term exposure durations are 

summarized below:

 Soybean – 281,250 lb, and

 Cotton – 339,500 lb.

Amount of Seed Planted (ASP, lb seed/A)

 Soybean – 133 lb seed/A = 200,000 seeds/A x lb soybean seeds/1,500 soybean seeds

 Cotton – 18.9 lb seed/A = 85,000 seeds/A x lb cotton seeds/4,500 cotton seeds

The amount of seed planted per day is summarized below:

 Soybean – 26,600 lb (133 lb seed/A × 200 A/day).

 Cotton – 3776 lb (18.9 lb seed/A × 200 A/day).

Exposure Duration: 

HED classifies exposures from 1 to 30 days as short-term and exposures 30 days to six months 

as intermediate-term.

Mitigation/Personal Protective Equipment: Results are presented for PPE (gloves); defined as a 

single layer of clothing consisting of a long sleeved shirt, long pants, shoes plus socks, protective 

gloves, and no respirator for all scenarios, except bagging and sewing, for which “baseline” attire 

was evaluated.

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.
Page 17 of 22

Summary of Occupational Handler Non-Cancer Exposure and Risk Estimates

The results of the occupational handler exposure and risk assessment indicate that short-term 

dermal and inhalation risk estimates do not exceed HED’s LOC (i.e. an MOE < 100 for shortterm exposures). Short-term exposure risk estimates are protective of intermediate-term 

exposure risk estimates because the throughput (amount of seed treated) of short-term exposure 

is greater than, or equal to, the throughput of intermediate-term exposure. The dermal MOEs 

range from 480 to 7,300 for handlers (treaters and planters). The inhalation MOEs range from 

620 to 26,000 for handlers (treaters and planters). Because the short- and intermediate-term 

dermal and inhalation PODs are the same, and the intermediate-term exposure inputs are less 

conservative than the short-term exposure inputs for seed treatment, short-term exposure risk 

estimates are protective of intermediate-term exposure risk estimates.

Table 6.1.2. Summary of Short- and Intermediate-Term Handler Exposures and Risk Estimates for Fluopyram 

Seed Treatment of Cotton and Peanut Seed.

a

Crop

Maximum 

Application 

Rateb

lb ai/lb 

seed

Amount of 

Seed Treated 

or Planted 

Per Dayd

lb seed/day

Dermal

Unit 

Exposurec

mg/lb

Inhalation

Unit 

Exposurec

mg/lb

Dermal 

Dosee

mg/kg/day

Inhalation 

Dosef

mg/kg/day

Dermal 

MOEf

LOC = 100

Inhalation 

MOEh

LOC = 100

Loader/Applicator

Soybean 0.001983 281,250

0.023 0.00034

0.1603 0.002370 1,900 6,100

Cotton 0.003472 339,500 0.3389 0.005010 890 2,900

Sewer

Soybean 0.001983 281,250

0.0062 0.00023

0.04322 0.001603 6,900 9,000

Cotton 0.003472 339,500 0.09135 0.003389 3,300 4,300

Bagger

Soybean 0.001983 281,250

0.0091 0.00016

0.06344 0.001115 4,700 13,000

Cotton 0.003472 339,500 0.1341 0.002357 2,200 6,200

Multiple Activities

Soybean 0.001983 281,250

0.042 0.0016

0.2928 0.01115 1,000 1,300

Cotton 0.003472 339,500 0.6188 0.02357 480 620

Planters

Soybean 0.001983 26,600

0.25 0.0034

0.1648 0.002242 1,800 6,500

Cotton 0.003472 3776 0.04099 0.0005574 7,300 26,000

a Seed treatment rate calculations are based on the following assumptions:

Soybean: 3,600 seeds per lb; 133 lb of seed planted per acre, 200 acres planted per day.

Cotton: 4,500 seeds per lb; 18.9 lb of seed planted per acre, 200 acres planted per day.

b Application Rate based on proposed label for fluopyram (Fluopyram ST, EPA Reg. No. 264-RRAT).

c Unit Exposures from HED Exposure Science Advisory Council Policy 14: Standard Operating Procedures for Seed Treatment (baseline 

inhalation = no respirator; dermal unit exposure includes PPE with gloves for loading/applicator, multiple activities and planter scenarios).

d 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).

e Daily Dermal Dose (mg/kg/day) = daily dermal unit exposure (mg/lb ai) × application rate (lb ai/lb seed) × amount planted (lb seed/day) ÷ 

body weight (80 kg adult).

f 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).

g Dermal MOE = NOAEL (300 mg/kg/day for short- and intermediate-term exposure) ÷ Dermal Dose (mg/kg/day). Level of concern = 100.

h Inhalation MOE = NOAEL (14.5 mg/kg/day for short- and intermediate-term exposure) ÷ Inhalation Dose (mg/kg/day). Level of concern = 

100.
Page 18 of 22

On-Farm Seed Treatment

On-farm seed treatment utilizes similar machinery as commercial seed treatment; the only 

difference being the size of the equipment. The assessed commercial seed treatment exposure 

and risk is protective of on-farm seed treatment scenarios.

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

There are multiple potential sources of post-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 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The agency has 

evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent 

Volatilization Screening Analysis (http://www.regulations.gov/#!docketDetail;D=EPA-HQOPP-2014-0219). During Registration Review, the agency will utilize this analysis to determine 

if data (i.e., flux studies, route-specific inhalation toxicological studies) or further analysis is 

required for fluopyram].

In addition, the Agency is continuing to evaluate the available post-application inhalation 

exposure data generated by the Agricultural Reentry Task Force. Given these two efforts, the 

Agency will continue to identify the need for and, subsequently, the way to incorporate 

occupational post-application inhalation exposure into the agency's risk assessments.

Although a quantitative occupational postapplication 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 postapplication exposure. Therefore, it is expected that these handler 

inhalation exposure estimates would be protective of most occupational postapplication 

inhalation exposure scenarios.”
Page 19 of 22

6.2.2 Occupational Post-application Dermal Exposure/Risk Estimates

In-Furrow Use on Cotton & Peanut

Occupational Post-application Dermal Exposure Data and Assumptions

In addition to the application rate and bodyweight values discussed above in the handler 

exposure section, the following assumptions were made in assessing short- and intermediateterm dermal post-application risks:

Dislodgeable foliar residues:

There were no chemical-specific dislodgeable foliar residue data to assess post-application risks 

to workers while performing tasks related to crops treated with fluopyram. For agricultural 

crops, occupational post-application exposures and risks were assessed using HED’s default 

assumptions that 25% of the initial application is available for transfer on day 0 (i.e., 12 hours 

after application) and that the residue dissipates at a rate of 10% per day. 

Transfer Coefficients:

HED uses a concept known as the transfer coefficient to numerically represent the postapplication exposures one would receive (generally presented as cm2

/hour). A transfer 

coefficient is a measure of the residue transferred from a treated surface to a person who is doing 

a task or activity in a treated area. These values are the ratio of an exposure for a given task or 

activity to the amount of pesticide residue on treated surfaces available for transfer. HED has 

developed a series of standard transfer coefficients that are unique for variety of job tasks or 

activities that are used in lieu of chemical- and scenario-specific data. 

No post-application data were submitted in support of this registration action; therefore, dermal 

exposures during post-application activities were estimated for the various tasks that postapplication workers might perform on each crop grouping using dermal transfer coefficients 

from the Science Advisory Council for Exposure Policy Number 3 

(http://www.epa.gov/pesticides/science/exposac_policy3.pdf). This policy reflects adoption of 

all ARTF data. Use of the data in this policy requires compensation to the ARTF under FIFRA. 

The transfer coefficients used in this assessment were taken from the Agency’s revised 

Agricultural Transfer Coefficient SOP. Many of the transfer coefficients in this SOP are based 

on work of the ARTF. 

Workday:

HED assumes an 8 hour workday for post-application workers.

Equations and Calculations:

Daily Dermal Exposure and default DFR calculations are presented below. Daily Dermal Dose 

and MOE calculations are the same as presented above in Section 6.1.

Daily Dermal Exposure: Daily dermal exposures were calculated on each post-application day 

after application using the following equation:
Page 20 of 22

DE(t) (mg/day) = (DFR(t) (μg/cm2) x TC (cm2/hr) x Hr/Day)/1,000 (μg/mg)

Where:

DE(t) = Daily exposure or amount deposited on the surface of the skin at time (t) 

attributable for activity in a previously treated area,

DFR(t) = Dislodgeable foliar residue (or transferable turf residue) at time “t” (μg/cm2),

TC = Transfer Coefficient (cm2/hour), and

Hr/day = Exposure duration meant to represent a typical workday (8 hours).

Default DFR: Default dislodgeable foliar residue (DFR) values were calculated on each postapplication day after application using the following equation:

Default DFR (μg/cm2) = AR (lb ai/A) x F x (1- D)tx CF1 x CF2

Where:

AR = Maximum application rate,

F = Fraction of ai retained on the foliage,

D = Fraction of residue that dissipates daily,

t = Post-application day,

CF1 = 4.54E+8 μg/lb, and

CF2 = 2.47E-8 A/cm2.

The post-application exposure associated with agricultural crops is summarized in Table 6.2.2.

The occupational post-application MOEs do not exceed HED’s level of concern (MOEs ≥100) 

with dermal MOEs ranging from 2,600 to 69,000. 

Table 6.2.2. Summary of Occupational Non-Cancer Post-application Risks (Short- and Intermediate-Term) 

with HED Default Assumptions.

Crops

Application 

rate

(lb ai/acre)

Default DFR on 0 

days (12 hr) after 

applicationa

(μg/cm2)

Work Activity & 

Maximum Transfer 

Coefficientb

(cm2/hr)

Daily Dosec

(mg/kg/day)

MOEd

(LOC = 100)

Peanut 0.22 0.617

1,900 Irrigation (Hand Set) 0.1172 2,600

210 Scouting 0.01295 23,000

70 Weeding (Hand) 0.004317 69,000

Cotton 0.22 0.617

210 Scouting 0.01295 23,000

70 Weeding (Hand) 0.004317 69,000

a. Default DFR (μg/cm2) = application rate (lb ai/A) x (1- daily dissipation rate) t x 4.54E+8 μg/lb x 24.7E-9 A/cm2 x 

25% DFR after initial treatment.

b. Crops were assessed using the highest transfer coefficient (TC) available.

c. Daily Dose = DFR x TC x (1 mg/1000 μg) x ET (8 hr/day) / body weight (80 kg)

d. MOE = NOAEL (300 mg/kg/day) / Daily Dose (mg/kg/day)

Restricted Entry Interval

Since post-application risk estimates were not a concern on day 0 (12 hours following 

application), the REI is based on the acute toxicity of fluopyram technical material. Fluopyram

is classified as Toxicity Category III by the acute dermal route of exposure and Toxicity 

Category IV for acute eye irritation potential and skin irritation potential. Under the WPS for 

Agricultural Pesticides, active ingredients classified as acute toxicity categories III or IV for 
Page 21 of 22

these routes are assigned a 12-hour REI. Therefore, the 12-hour REI that appears on the 

proposed Luna® Privilege label is adequate.

Seed Treatment Use on Cotton & Soybean Seeds

With regard to seed treatment, the potential for post-application exposures following the planting 

of fluopyram-treated seeds is unlikely because sustained levels of contact with treated seed after 

it has been placed in the soil or other planting media would not be expected because no routine 

cultural practice required for the production of agricultural commodities involves such an 

activity, as defined in the no/low contact criteria in the Worker Protection Standard (WPS). 

Therefore, no quantitative post-application assessment is required for exposure to treated seeds 

that have already been planted.
Page 22 of 22

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).