Date: 

Subject: 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

01-SEP-2015 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

Flutriafol. Occupational and Residential Exposure Assessment for a Proposed 

Use on Hops 

PC Code: 128940 

Decision No.: 492995 

Petition No.: NIA 

DP Barcode: 0426919 

Registration No.: 67760-75 

Regulatory Action: Section 3 

Risk Assessment Type: Occupational/Residential Case No.: 7060 

Exposure Assessment 

TXRNo.: NA 

MRIDNo.: NA 

CAS No.: 76674-21-0 

40 CFR: § 180.629 

From: 

Through: 

To: 

Introduction 

Kelly 

Risk Assessment 

M. Lowe, Environmental 

Branch 1 (RAB 

Scientist 

1) 

/;\(~('.'.:'

· 

.~ 

Health Effects Division (7509P) 

Thurston Morton, Acting Branch Chief 

Health Effects Division (7509P) 

and 

Kristin Rury, ExpoSAC Reviewer V;--~ Ivan Nieves, ExpoSAC Reviewer / ~ .. ' J--d---

Exposure Science Advisory Committe ExpoSAC) I HED 

Tamue Gibson, RM21 

Fungicide Branch 

Registration Division (7505P) 

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

exposure and risk assessment for a proposed use of flutriafol on hops. A quantitative assessment 

of occupational handler exposure has not been conducted since a previous assessment (D416213) 

covers handler exposure from the proposed use. However, post-application exposure from the 

proposed use is not covered by the previous assessment and has been included here. 

Page I of 15 
Page 2 of 15

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 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 30-APR-2015.
Page 3 of 15

Table of Contents

1.0 Executive Summary............................................................................................................. 4

2.0 Risk Assessment Conclusions and Recommendations........................................................ 5

2.1 Summary of Risk Estimates............................................................................................. 5

2.2 Label Recommendations.................................................................................................. 5

2.3 Data Deficiencies and Requirements ............................................................................... 6

3.0 Hazard Characterization....................................................................................................... 6

4.0 Exposure and Use Profile..................................................................................................... 7

5.0 Residential Exposure and Risk Estimates............................................................................ 8

5.1 Spray Drift........................................................................................................................ 8

5.2 Residential Bystander Post-Application Inhalation Exposure ......................................... 8

6.0 Occupational Exposure and Risk Estimates ........................................................................ 9

6.1 Occupational Handler Exposure/Risk Estimates.............................................................. 9

6.2 Occupational Post-application Exposure/Risk Estimates ................................................ 9

6.2.1 Occupational Post-application Inhalation Exposure/Risk Estimates........................ 9

6.2.2 Occupational Post-application Dermal Exposure/Risk Estimates.......................... 10

Appendix A. Summary of Occupational Non-cancer Algorithms............................................... 14
Page 4 of 15

1.0 Executive Summary

Flutriafol [(±)-α-(2-fluorophenyl)-α-(4-fluorophenyl)-1H-1, 2,4-triazole-1-ethanol] is a systemic, 

triazole fungicide that can be used as a systemic eradicant and a protectant. It has a postinfection activity that can stop pathogen establishment in the early phases of disease 

development. It is currently registered for use on a variety of agricultural crops. 

Exposure and Proposed Use Profile

The proposed use on hops is to be added to the TopGuard® Fungicide (EPA Reg. #: 67760-75)

label. The proposed maximum single application rate is 0.114 lb ai/A, and is to be made to the 

foliage via aerial or airblast applications. The product cannot be applied via chemigation. The 

foliar applications are allowed for up to four times per season, with a retreatment interval of 7 

days. The restricted entry interval for the proposed use is 12 hours. Personal protective 

equipment (PPE) listed on the proposed label includes long-sleeved shirt and long pants,

chemical-resistant gloves, and shoes plus socks. Based on the proposed use pattern, it has been 

determined that the potential exposure scenarios are short- and intermediate-term handler and 

post-application occupational exposures. 

Hazard Profile

The short- (1-30 days), and intermediate- (1-6 months) term dermal and inhalation toxicological 

points of departure (PODs) were identified from a prenatal developmental toxicity study in the 

rabbit where the effects were based on decreased number of live fetuses, complete litter 

resorptions, and increased post-implantation loss. The no-observed adverse-effect level 

(NOAEL) was 7.5 mg/kg/day. Flutriafol was classified as a “not likely” human carcinogen 

based on carcinogenicity studies in rats and mice. The total uncertainty factor (UF) that was 

applied to occupational and residential risk assessments is 100 for short- and intermediate-term 

risks (10x interspecies factor, 10x intraspecies factor). Since the POD for the dermal and

inhalation routes of exposure are based on the same effect, the exposures from these routes can 

be combined to estimate total risk. Since the dermal and inhalation PODs are based on 

developmental and/or fetal effects, the body weight appropriate for dermal and inhalation 

assessments is 69 kg.

Residential Exposure and Risk

There are no residential uses proposed or currently registered for flutriafol. Therefore, 

residential handler and post-application exposure/risk were not assessed. 

Occupational Exposure and Risk

A new occupational handler assessment was not conducted since the anticipated exposure 

scenarios (mixing/loading and applying via aerial and airblast equipment), maximum application 

rate (0.114 lb ai/A), and recommended level of PPE have been assessed in a previous assessment

(D416213). The combined occupational dermal plus inhalation handler exposure and risk 

estimates were not of concern in those assessments (i.e., MOE > 100) at baseline and with the 

use of gloves, as is required on the proposed label. 

Although the anticipated occupational handler scenarios for hops have been covered by a 

previous assessment (D416213) that included the same maximum application rate and 
Page 5 of 15

equipment, the anticipated post-application scenarios have been assessed for the proposed use 

because the worker activities are unique to the proposed crop. The occupational post-application 

dermal exposure and risk estimates are greater than the level of concern (LOC) of 100 on the day 

of application, ranging from 510 to 4,200. Since the post-application assessment is not a concern 

on Day 0 (12 hours following application), the restricted entry interval (REI) is based on the 

acute toxicity of flutriafol technical material. Flutriafol has low acute toxicity via the oral, 

dermal and inhalation routes (Toxicity Categories III and IV), is minimally irritating to the eyes 

(Toxicity Category III), and is not a dermal irritant (Toxicity Category IV). Flutriafol was not 

shown to be a skin sensitizer when tested in guinea pigs (Buehler method). Therefore, the acute 

toxicity categories for this chemical require a 12 hour REI under 40 CFR 156.208 (c) (2) (iii). 

The 12-hour REI, which currently appears on the proposed label, is adequate for the proposed 

use.

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

inhalation exposure assessment was not performed for flutriafol 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 flutriafol.

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 

the ARTF database 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

Based on a previous assessment for flutriafol (D416213) which included an occupational handler 

assessment that covers the proposed use, there are no occupational handler risk estimates of 

concern for the proposed use on hops. In addition, there are no occupational post-application 

risk estimates of concern based on the current assessment. 

• In the previous assessment, occupational handler MOEs ranged from 280 to 30,000 for 

aerial and airblast applications.

• The occupational post-application dermal exposure and risk estimates range from 510 to 

4,200 depending on the activity on the day of application. 

2.2 Label Recommendations 

There are no label recommendations based on the proposed uses.

 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 15

2.3 Data Deficiencies and Requirements

None. 

3.0 Hazard Characterization

Flutriafol has low acute toxicity via the oral, dermal and inhalation routes (Toxicity Categories 

III and IV). Flutriafol is minimally irritating to the eyes (Toxicity Category III) and is not a 

dermal irritant (Toxicity Category IV). Flutriafol was not shown to be a skin sensitizer when 

tested in guinea pigs (Buehler method). Table 3.1 presents a summary of the acute toxicity 

information for flutriafol.

Table 3.1. Acute Toxicity Profile – Flutriafol.

Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral (rat) 47090336 LD50 = 1140 mg/kg (M); 

1480 mg/kg (F) III

870.1200 Acute dermal (rat) 47090337 LD50 > 2000 mg/kg III

870.1300 Acute inhalation (rat) 47090338 LC50 > 5.20 mg/L IV

870.2400 Primary eye irritation 

(rabbit) 47090339 Minimally irritating III

870.2500 Primary dermal irritation 

(rabbit) 47090341 Not a dermal irritant IV

870.2600 Dermal sensitization 

(guinea pigs) 47090343 Not a sensitizer -

Flutriafol appears to be generally equally toxic to rats, mice, and dogs with all three species 

having similar (within one order of magnitude) NOAELs/lowest-observed adverse-effect levels 

(LOAELs). The target organ is the liver in dogs, rats, and mice. Hepatotoxicity occurred at 

similar dose levels across several species and durations of exposure. Flutriafol is considered to 

be “Not likely to be Carcinogenic to Humans” based on the results of the carcinogenicity studies 

in rats and mice. 

The Hazard and Science Policy Council (HASPOC) met on December 12, 2013 to discuss the 

need for a subchronic inhalation toxicity study for flutriafol. Based on a weight of evidence 

approach, the HASPOC concluded that a subchronic inhalation toxicity study was not needed for 

flutriafol at this time for the following reasons: (1) flutriafol is category IV for acute toxicity 

through the inhalation route and the effects in that study were seen at a very high concentration 

of 5.2 mg/L; (2) following the ORE inhalation risk assessment at the time, the lowest inhalation 

MOE was 17,000; and (3) the HAPSOC waived the requirement for an inhalation study for 

cyproconazole, a similar broad spectrum triazole fungicide. 

A summary of the toxicological endpoints and doses chosen for the relevant exposure scenarios 

for human risk assessment are found in Table 3.2. The short- (1-30 days), and intermediate- (1-6 

months) term dermal and inhalation toxicological PODs were identified from a prenatal 

developmental toxicity study in the rabbit where the effects were based on decreased number of 

live fetuses, complete litter resorptions and increased post-implantation loss. The NOAEL was 

7.5 mg/kg. 
Page 7 of 15

The Agency’s LOC for risks (i.e., target level for Margins of Exposure) is defined by the 

uncertainty factors that are applied to the assessment. The Agency applies a factor of 10X to 

account for interspecies extrapolation to humans from the animal test species and another factor 

of 10X to account for intra-species sensitivity. The total uncertainty factor that has been applied 

to occupational risk assessments is 100 for short- and intermediate- term dermal and inhalation 

exposures. 

Absorption

Since an oral study was used, a dermal absorption factor of 21% was used for the dermal risk 

assessment derived from a dermal penetration study (MRID 47090415). 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

Since the dermal and inhalation PODs are based on developmental and/or fetal effects, the body 

weight appropriate for dermal and inhalation assessments is 69 kg.

Table 3.2: Summary of Toxicological Doses and Endpoints for Flutriafol.

Exposure/

Scenario

Point of 

Departure

Uncertainty/FQPA 

Safety Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Dermal

Short (1-30 

days)- and 

Intermediate 

(1-6 months) -

Term 

NOAEL=7.5

mg/kg/day 

Dermal 

Absorption 

Factor = 21%

UFA = 10X

UFH = 10X

Occupational 

LOC for MOE 

= 100

Developmental toxicity – rabbit

LOAEL = 15mg/kg, based on decreased number 

of live fetuses, complete litter resorptions and 

increased post-implantation loss. 

Inhalation 

Short (1-30 

days)- and 

Intermediate 

(1-6 months) -

Term 

NOAEL = 

7.5 

mg/kg/day

Inhalation 

toxicity 

assumed to 

be equivalent 

to oral 

toxicity.

UFA = 10X

UFH = 10X

Occupational 

LOC for MOE 

= 100

Developmental toxicity – rabbit

LOAEL = 15 mg/kg, based on decreased number 

of live fetuses, complete litter resorptions and 

increased post-implantation loss. 

Cancer (oral, 

dermal, 

inhalation)

Classification: “Not likely to be Carcinogenic to Humans” based on the carcinogenicity studies in 

rats and mice. 

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 (intraspecies). UFH = 

potential variation in sensitivity among members of the human population (interspecies). MOE = margin of exposure. LOC = level of concern. 

4.0 Exposure and Use Profile 

Flutriafol is registered for use on a number of agricultural crops, and is being proposed for a use 

on hops. Based on the proposed new use, it has been determined that the potential exposure 
Page 8 of 15

scenarios include short- and intermediate-term occupational handler and post-application 

exposures. A summary of the proposed use directions are included in Table 4.1 below. 

Table 4.1. Summary of Proposed Use Directions for Flutriafol.

Applic. Timing, Type, and 

Equip.

Formulation 

[EPA Reg. No.]

Application 

Rate

Max No. 

Applications 

per Season

Max Seasonal 

Application 

Rate

Use Directions and 

Limitations

TopGuard® Fungicide1 (67760-75) 1.04 lb ai/gal (11.8% ai)

Hops

Apply preventatively or when 

conditions are favorable for 

disease development. Repeat 

as necessary if conditions are

favorable for disease

development.

Airblast or Aerial.

Liquid 

(67760-75) 

0.114 lb 

ai/A

4 apps/growing 

season 0.455 lb ai/A

Do not apply via 

chemigation. REI = 12 

hours. RTI = 14 days. 

PHI = 7 days.

5.0 Residential Exposure and Risk Estimates

There are no residential uses proposed or currently registered for flutriafol. Therefore, 

residential handler and post-application exposure/risk were not assessed. 

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 flutriafol. 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 has also developed a policy on how to 

appropriately consider spray drift as a potential source of exposure in risk assessments for 

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. The approach is outlined in the revised (2012) Standard Operating Procedures 

For Residential Risk Assessment (SOPs) - Residential Exposure Assessment Standard Operating 

Procedures Addenda 1: Consideration of Spray Drift. This document outlines the quantification 

of indirect non-occupational exposure to drift. 

5.2 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 

 2 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm 
Page 9 of 15

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

flutriafol.

6.0 Occupational Exposure and Risk Estimates

6.1 Occupational Handler Exposure/Risk Estimates

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

techniques that can be used, occupational handler exposure is expected. The following exposure 

scenarios would be expected: (1) Mixing/loading liquids for aerial and airblast applications; (2) 

applying sprays via aerial and airblast equipment; and (3) flagging for aerial applications.

These scenarios have already been assessed at the proposed maximum application rate in a 

previous assessment (D4162133

), and no risk estimates of concern were identified. The dermal 

and inhalation combined MOEs were not of concern to HED (i.e., MOE > 100) at baseline and 

with the use of gloves as recommended by the proposed label. Combined occupational handler 

MOEs ranged from 280 to 30,000 for aerial and airblast applications with the use of gloves by 

mixers/loaders.

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 

 3 Memo, K. Lowe, D416213, 1/24/14, Flutriafol. Occupational and Residential Exposure Assessment for Proposed 

Uses on Cucurbit Vegetables, Fruiting Vegetables, Strawberries, Tree Nuts, Wheat/Triticale, Brassica (cole) Leafy 

Vegetables, Celery, Leafy Vegetables, Cotton, Sorghum
Page 10 of 15

(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 flutriafol.

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 post-application inhalation exposure assessment was not 

performed, an inhalation exposure assessment was performed previously 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.

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. 

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

days to six months as intermediate-term. For flutriafol, short- and intermediate-term exposures

are expected for the following reasons: (1) flutriafol is a fungicide that is recommended to be 

applied preventatively or when conditions favor disease; and (2) up to 4 foliar applications can 

be made per season 14 days apart. In addition, the short- and intermediate-term PODs are the 

same; therefore, the 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 34

” which, along with 

additional information about the ARTF data, can be found at the Agency website5. 

It should be noted that the transfer coefficient used for assessing exposure from mechanicallyassisted harvesting is different from ExpoSAC Policy 3. For this proposed action on hops, the 

 4 Available: http://www.epa.gov/pesticides/science/exposac_policy3.pdf 5 Available: http://www.epa.gov/pesticides/science/post-app-exposure-data.html
Page 11 of 15

Registrant submitted an occupational post-application exposure assessment (MRID 49421701) 

which used a revised transfer coefficient for mechanically-assisted harvesting, citing an ARTF 

report (MRID 49157401) that evaluated current harvesting practices in hops, and recommended 

a different transfer coefficient from what is currently recommended in ExpoSAC Policy 3. HED 

has reviewed the ARTF report, and has revised the transfer coefficient for harvesting of hops 

based on the available information (D413084). 

Table 6.2.2.1. Summary of Post-Application Activities and Dermal Transfer Coefficients.

Crop

Policy Crop 

Group 

Category

Crop Height Foliage 

Density

Transfer 

Coefficients 

(cm2/hr)

Activities

Hops Bunch/bundle

Low/High Full/Minimum 0

Irrigation (non-hand set), 

Mechanical weeding, Ditching, 

Mechanical harvesting

Low Minimum 230 Transplanting

Low/High Full/Minimum 640 Hand weeding, Stripping, 

Scouting, Tying/Training

High Full 1,400 Mechanically-assisted 

harvesting

High Full 1,900 Irrigation (hand-set)

Application Rate:

The application rates used in this assessment are provided in Table 4.1.

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 flutriafol. 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.

Occupational Post-application Non-Cancer Dermal Exposure and Risk Estimate Equations

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 short- and intermediate-term post-application exposure scenarios associated with the 

proposed use for flutriafol are summarized in Table 6.2.2.2. All scenarios resulted in MOEs 

greater than the LOC of 100 (ranging from 510 to 4,200) on day 0 (12 hours after application) 

and, therefore, are not of concern to HED.
Page 12 of 15

Table 6.2.2.2. Occupational Post-application Non-Cancer Exposure and Risk Estimates for Flutriafol.

Crop/Site Activities

Transfer 

Coefficient 

(cm2/hr)

Proposed 

Application 

Rate (lb ai/A)

DFR1 Dermal Dose 

(mg/kg/day)2

MOE3

(LOC = 

100)

Short- and Intermediate-term

Hops

Transplanting 230

0.114 0.32

0.0018 4,200

Hand weeding, 

Stripping, Scouting, 

Tying/Training

640 0.00498 1,500

Mechanically-assisted 

harvesting 1,400 0.011 690

Irrigation (hand-set) 1,900 0.015 510

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 (21%)] ÷ BW (69 kg).

3 MOE = POD (7.5 mg/kg/day) / Daily Dermal Dose. 

Dislodgeable Foliar Residue (DFR): 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 postapplication 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 flutriafol, 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 flutriafol (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).
Page 13 of 15

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 

flutriafol 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 = 510 compared to the LOC of 100); EPA is 

waiving the 40CFR DFR data requirement. In this instance, it is unlikely that chemical-specific 

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 

flutriafol. 

Restricted Entry Interval

The REI specified on the proposed label is based on the acute toxicity of flutriafol. Flutriafol has 

low acute toxicity via the oral, dermal and inhalation routes (Toxicity Categories III and IV). 

Flutriafol is minimally irritating to the eyes (Toxicity Category III) and is not a dermal irritant 

(Toxicity Category IV). Flutriafol was not shown to be a skin sensitizer when tested in guinea 

pigs (Buehler method). Short- and intermediate-term post-application risk estimates were not a 

concern on day 0 (12 hours following application) for all post-application activities. Under 40 

CFR 156.208 (c) (2) (iii), ai’s classified as Acute III or IV for acute dermal, eye irritation and 

primary skin irrigation are assigned a 12-hour REI. Therefore, the [156 subpart K] Worker 

Protection Statement interim REI of 12 hours is adequate to protect agricultural workers from 

post-application exposures to flutriafol. 
Page 14 of 15

Appendix A. Summary of Occupational Non-cancer Algorithms

Occupational Non-cancer Post-application Algorithms

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:
Page 15 of 15

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).