### Date :

Subject: UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

24-JAN-2014 OFFICE OF CHEMICAL SAFETY
AND POLLUTION PREVENTION



### Flutriafol. Occupational and Re sidential Exposure Assessment for Proposed

Uses on Cucurbit Vegetables, Fruiting Vegetables

, Strawberries, Tree Nuts, Wheat/Triticale, Brassica (cole) Leafy Vegetables, Celery, Leafy Vegetables, Cotton, Sorghum

PC Code: 128940 DP Barcode: 0416213, 0416214

, 0416216 Registration No.: 67760-75, 67760-REN Regulatory Action: Section 3 Decision No.: 475694, 4 78287, 482872
Petition No. : N / A
Risl< Assessment Type: Occupational/Residential

E xpo su re Assessment Case No.: 7060

TXR No.: NA

MRID No.: 47090415 CAS No.: 76674-21-0
40 CFR: § 180.629



### From:

Through:

To:

I ntroduction Kelly M. Lowe, Environmental

### Scientist~~ Risk Assessment Branch 1 (RAB 1)**~ ~**  - 

# bu ·
Heal th Effec t s Division (7509P)

Charles W. Smith, Branch

# Chief**~ ~**  Health Effects Division

### (7509P**~**

and

Sha l u Shelat, Reviewer

# ~~**·** · Ivan Nieves, Reviewer 

# ..-r .-- ___. Exposure Science Advisory Co mittee (ExpoSAC) I H ED

Tamue Gibson

, RM21 Fungicide Branch Registration Di vision (7505P)

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

exposure and risk assessment for three actions related to flutriafol: ( 1 ) new uses on cucurbit vegetables, f ruiting vegetab les

, strawberries, tree nuts, and

wheat /t riticale (D4 16 216); (2) new uses on Brassica (cole) leafy vegetables, celery, leafy vegetables, cotton, and

Pa ge 1 of23sorghum (D4 1 6213); and (3) an amendment to t h e to l erances for field corn and popcorn (D4 1 6214).

A quantitative assessment of occupationa l exposure has been conducted for all of the proposed

uses of flutriafol (D416216 and D416213); however, it was determined that an exposure

assessment was not necessary for the corn to l erance amendment (D416214) s i nce corn is a
reg i stered use site and has been assessed previously. The proposed tolerance changes do not impact the use pattern or application rate for the r egistered use on com, and, therefore

, a revised

exposure assessment is not required. The previous assessment (Memo, 

### K. Lowe, 9 / 20111, D383037) provides the exposure and risk estimates for this use.

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 chemica l -specific data, including Pesticide Handlers Exposure Database Version 1

. 1 (PHED 1

. 1 ); the Agricultural

Handler Exposure Task Force (AHETF) database; the Outdoor Residential Exposure Task Force (ORETF) database; and the Agricultural Reentry Task F orce (ARTF) database. Some of these
data are proprietary, and subject to the data protection provis i ons of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA).

Note: This memorandum was reviewed by the E xposure Science Advisory Committee (ExpoSAC) on 12

- DEC-2013.

. P a ge 2 of23Page 3 of 23 

### T able 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

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

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

................................ ................................ ................................ ....... 6
4.0 Ex posure and Use Profile

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

................................ ................................ .......... 10
5.1 Spray Drift

................................ ................................ ................................ ...................... 10
5.2 Residential Bystander Post

- Application Inhalation Exposure

................................ ....... 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

................................ .............. 17
6.2.1 Occupational Post

- application Inhalation Exposure/Risk Estimates

...................... 17
6.2.2 Occupational Post

- applicat ion Dermal Exposure/Risk Estimates

.......................... 18 Appendix A. Summary of Occupational Non

- cancer Algorithms

................................ ............... 21Page 4 of 23



### 1.0 Executive Summary

Flutriafol [(±)

- α

- (2

- fluorophenyl)

- α

- (4

- fluorophenyl)

- 1 H

- 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 post

infection activity that can stop pathogen establishment in the early phases of disease development. It is currently registered for use on a variety of agricultural c rops, including corn, grapes, soybeans, apples, peanuts, pome fruit, stone fruit, and sugarbeets. Cheminova is requesting three actions related to flutriafol: (1) new uses on cucurbit vegetables, fruiting vegetables, strawberries, tree nuts, and wheat/triticale (D416216); (2) new uses on Brassica (cole) leafy vegetables, celery, leafy vegetables, cotton, and sorghum (D416213); and (3) an amendment to the tolerances for field corn and popcorn (D416214).

Exposure and Proposed U se Profile The proposed uses involve three labels: Flutriafol® 250 g/L ( EPA Reg. #: 67760

- REN)

, TopGuard® Fungicide ( EPA Reg. #: 67760

- 75) , and Flutriafol® 500 g/L ( EPA Reg. #: 67760

- REA) . The proposed new uses are on cucurbit vegetables, fruiting vegetables, strawberries, tree nuts, wheat/triticale

, Brassica (cole) leafy vegetables, celery, leafy vegetables, cotton, and sorghum . All of the uses are propose d at a maximum application rate of 0.114 lb ai/A

, to be made to the foliage via aerial, groundboom or airblast applications. None of the uses allow for application via chemigation. There is one proposed soil

- directed application of flutriafol for

cotton at a rate of 0.26 lb ai/A (one application per season). The foliar applications are allowed for up to four times per season, with a retreatment interval of 7 days. The restricted entry interval for all the proposed uses is 12 hours. Based on the propose d use pattern , it has been determined that the potential exposure scenarios that will need to be assessed include short

- and
intermediate

- term occupational exposures (handler and post

- application).

Hazard Profile
The short

- (1

- 30 days), and intermediat e

- (1

- 6 months) term dermal and inhalation toxicological points of departure 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
increa sed post

- implantation loss. The NOAEL was 7.5 mg/kg /day . Flutriafol was classified as a “not likely” human carcinogen based on the carcinogenicity studies in rats and mice. The total uncertainty factor (UF) that was applied to occupational and residential risk assessments is 1 00
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

.

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 Expo sure and Risk The occupational handler exposure and risk estimates indicate that the short

- and intermediate

term dermal and inhalation combined MOEs are not of concern to HED (i.e., MOE > 1 00) with
the use of chemical

- resistant gloves as directed by the l abel. At the baseline level of personal protection (i.e., no gloves and no respirator), only one scenario results in a risk estimate belowPage 5 of 23



### the LOC with a combined (dermal + inhalation) MOE of 8 2 ; this scenario is mixing/loading a liquid formulation for ae rial application to high acreage crops. With the addition of gloves, the combined dermal + inhalation MOE is 470, which is not of concern. All other scenarios result in risk estimates greater than 220 with baseline attire.

The occupational post

- application dermal exposure and risk estimates are greater than the LOC
of 1 00 on the day of application , ranging from 230 to 4,600 depending on crop and activity. 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 a nd 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 m ethod). 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 label s , is adequate for the proposed uses

.

Based on the Agency's current practic es, 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

pos t

- 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 includ e studies from the PHED 1.1, the AHETF database, and 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 website 1



### .

2.0 Risk Assessment Conclusions and Recommendations

2.1 Summary of Risk Estimates

There are no occupational risk estimates of concern for the proposed uses for flutriafol

. At the baseline level of personal protection (i.e., no gloves and no respirator), only one scenario results in a risk estimate below the LOC with a combined (dermal + inha lation) MOE of 8 2 ; this scenario is mixing/loading a liquid formulation for aerial application to high acreage crops. With the addition of gloves, the combined dermal + inhalation MOE is 470, which is not of concern.
All other scenarios result in risk es timates greater than 220 with baseline attire. The occupational post

- application dermal exposure and risk estimates are greater than the LOC of
1 00 on the day of application , ranging from 230 to 4

, 6 00 depending on crop and activity.

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

- exposure

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

- app

- exposure

- data.htmlPage 6 of 23



### 2.2 Label Recommend ations

There are no label recommendations based on the proposed uses.

2.3 Data Deficiencies and Requirements

Dislodgeable Foliar Residue (DFR): In accordance with the updated Part 158 data requirements (2007), one or more DFR studies are required when a pesticide has residential or occupational uses that could result in post

- application dermal exposure. As part of the recent revision to the Health Effects Division’s 2012 Standard Operating Procedures for Residential Pesticide Exposure Assessment , HED analyzed a number of DFR studies and selected a new default value for the fraction of the application rate available to be dislodged after a foliar application (F AR 

### ). This default value is 25% and is based on an analysis of 19 DFR studies where the F AR 

### va lue ranged from 2% to 89%. This value is recommended for use in both residential and occupational
post

- application assessments. Of the analyzed DFR studies, the maximum F AR 

### value seen was 89% or 3.6 times higher than the default residue transfer value. Therefore, the HED has decided that a calculated MOE of approximately 4 times higher than the level of concern (e.g., an MOE > 400 if the LOC = 100) using the default dislodged residue values would provide an adequate margin of safety for any potentially h igher residues seen in a chemical

- specific DFR study ( Guidance for Requiring/Waiving Turf Transferrable Residue (TTR) and Dislodgeable Foliar Residue (DFR) Studies . 12/12/2012, Exposure Science Advisory Council). A DFR study is required for flutriafol at this time since the dermal MOEs for leafy vegetables are less than 4 times the LOC ( i.e., 400 ) based on default values for the fraction of application rate available for transfer after a foliar application.

3 .0 Ha zard 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 LD 50 = 1140 mg/kg (M); 1480 mg/kg (F) III

870.1200 Acute dermal (rat) 47090337 LD 50 > 2000 mg/kg III

870.1300 Acute inhalation (rat) 47090338 LC 50 > 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) no

- observed adverse

- effect levelsPage 7 of 23



### (NOAELs)/lowest

- observed adverse

- effect levels (LOAELs). The target organ is t he 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 inha lation toxicity study is not needed for flutriafol at this time for the following reasons: (1) f lutriafol 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 ) f

ollowing the ORE inhalation risk assessment

, the lowest inhalation MOE is 17,000 ; and (3) the HAPSOC waived the requirement for an inhalation study for c yproconazole, 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 points of departure were identified from a prenatal deve lopmental 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. Flutriafol was classified as a “not likely” human carcinog en based on the carcinogenicity studies in rats and mice.

The Agency’s level of concern 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 pe netration study (MRID 47090415) . Since no inhalation absorpt ion 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 Dos es and Endpoints for Flutriafol

.

Exposure/
Scenario Point of

Departure Uncertainty/FQPA

Safety Factors RfD, PAD,

Level of
Concern for
Risk
Assessment Study and Toxicological EffectsPage 8 of 23

Table 3 .2: Summary of Toxicological Dos es 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% UF A = 10X

UF H = 10X FQPA SF = 1X 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. UF A = 10X

UF H = 10X FQPA SF = 1X 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 carcinogenic ity 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. UF A = extrapolation from animal to human (intraspecies). UF H = potential variation in sensitivity among members of the h uman population (interspecies). FQPA SF = FQPA Safety Factor. 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, including corn, grapes, soybeans, apples , peanuts, pome fruit, stone fruit, and sugarbeets

. Based on the proposed new

uses , it has been determined that the potential exposure scenarios that will need to be assessed
include short

- and intermediate

- term occupational exposures (handler and post

- ap plica tion)

. 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

Flutriafol® 250 g/L 1 (67760

- REN) 2.08 lb ai/gal (22.7% ai) TopGuard® Fungicide 1 (67760

- 75) 1.04 lb ai/gal (11.8% ai) Flutriafol® 500 g/L 1 (67760

- REA) 4.16 lb ai/gal (42% ai)
Brassica (cole) leafy vegetables, Celery, Leafy Vegetables
Apply preventatively or when
conditions are favorable for
disease.

Groundboom or Aerial. Liquid (67760

- REN) 0.114 lb

ai/A 4 apps/growing

season 0.455 lb ai/A Do not apply via chemigation. REI = 12 hours. RTI = 7 days. PHI = 7 days

Cotton

Apply preventatively or when Liquid 0.114 lb 2 foliar 0.488 lb ai/A Do not apply viaPage 9 of 23

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

conditions are favorable for
disease.

Groundboom or Aerial. (67760

- 75) ai/A app/season (including
both foliar and soil apps) chemigation. REI = 12

hours. RTI (for foliar applications) = 7 days. PHI = 30 days. Applied at planting to the soil.

Groundboom. Liquid (67760

- REA) 0.26 lb ai/A 1 soil app/season

Cucurbits (cucumbers, pumpkin, squash, watermelon, muskmelons)
Apply preventatively or when
conditions are favorable for
disease.

Groundboom 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 = 7 days.

PHI = 0 day. Liquid (67760

- REN)

Pecans (and other tree nuts), Almonds and Walnuts

For Pecan Scab control, start application at bud break;
continue 10

- 14 days pre

pollination and 14

- 21 days
post

- pollination. For all other diseases, apply preventatively
or when conditions are
favorable for disease.

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 = 7 days. PHI = 14 days. For Brown Rot Blossum Blight, start applications at 5

- 10% bloom, followed by an application at 50

- 100% bloom. For all other diseases, apply preventatively or when
conditions are favorable for
disease.

Airblast or Aerial. Liquid (67760

- REN)

Peppers (and Other Fruiting Vegetables), Tomatoes
Apply preventatively or when
conditions are favorable for
disease.

Groundboom 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 = 7 days. PHI = 0 day. Liquid (67760

- REN)

Wheat (spring and winter) and Triticale
For suppression of Fusarium Head Blight, apply at anthesis (or Pollination; beginning of flowering; Feekes Scale: 10.51). For all other diseases, apply preventatively or when
conditions are favorable for
disease.

Groundboom or Aerial. Liquid (67760

- 75) 0.114 lb

ai/A 2 apps/growing

season 0.203 lb ai/A Do not apply via chemigation. REI = 12
hours. RTI = 7 days. PHI = 30 days when grown for grain, 15 days when grown for hay, 0 day when grown for forage.

Strawberry
Apply preventatively or when
conditions are favorable for Liquid (67760

- REN) 0.114 lb

ai/A 4 apps/growing

season 0.455 lb ai/A Do not apply via chemigation. REI = 12Page 10 of 23

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

disease.

Groundboom or Aerial. hours. RTI = 7 days. PHI = 0 day.

Sorghum
For Ergot, make first application at or just prior to planting. For all other diseases, apply preventatively
or when conditions are
favorable for disease.

Groundboom or Aerial. Liquid

(67760

- 75) 0.114 lb

ai/A 4 apps/growing

season 0.455 lb ai/A D o not apply via chemigation. REI = 12 hours. RTI = 7 days. PHI = 7 days.

1. PPE = LS shirt and long pants; CR gloves; shoes/socks



### 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 h as 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 devel op 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

pe sticides 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 th at 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 flutriafol at thi s time primarily because of the low acute inhalation toxicity (Toxicity Category IV) and the low vapor pressure ( 3.0 x 10 - 9 

### mmHg, 2 0°C). However, volatilization of pesticides may be a source of post

- application inhalation exposure to individuals nearby pe sticide applications. The Agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act

2 Available: http://www.epa.gov/opp00001/ factsheets/spraydrift.htmPage 11 of 23



### Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final r eport on March 2, 2010 3



### . 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 Ag ency'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 flutriafol

.

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 dep ending 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 spec ific to each application event.

Based on the anticipated use patterns

, and the current labeling regarding types of equipment and techniques that can be used, occupation al handler exposure is expected . The quantitative exposure/risk assessment developed for occupational handlers is based on the following
scenarios:

1) Mixing/loading liquids for aerial, groundboom, and airblast applications; 2) Applying sprays via aerial , airblast and groundboom equipment; and 3) Flagging for aerial applications.

Occupational H andler 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 : The application rates used in this assessment 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

- sp ecific data, include PHED 1.1, the AHETF database, the Outdoor Residential Exposure Task Force (ORETF) database, or other registrant

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

### ” , which, along with additional information on HED policy

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

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

- exposure

- table.pdfPage 12 of 23



### on use of surrogate data, including descriptions of the various sources, can be found at the Agency website 5



### .

Area Treated or Amount Handled : The inputs for area treated were based on information in ExpoSAC Policy 9.1 and include:

1200 and 350 acres for aerial application to high and typical acreage crops , respectively

200 and 80 acres for groundboom application to high and typical acreage crops , respectively 40 acres for airblast applications

350 acres for flaggers

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, t he 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

- m onth time frame; however, there may be a large agribusiness and/or commercial applicators who may apply a product over a period of weeks

.

For the proposed use patterns , short

- and intermediate

- term exposures are anticipated for the following reasons: (1) flutriafol is a fungicide that is recommended to be applied preventatively
or when conditions favor disease ; (2) up to 4 foliar applications can be made per season 7 da ys apart ; and (3) commercial applicators may apply this product at various locations within a region over a period of weeks. In addition, the short

- and intermediate

- term PODs are the same; therefore, short

- term risk estimates are protective of longer

- ter m exposures.

Mitigation/Personal Protective Equipment: Estimates of dermal and inhalation exposure were calculated for various levels of personal protective equipment (PPE). Results are presented for “baseline,” defined as a single layer of clothing con sisting 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 flutriafol product labels direct mixers, loaders, appl icators and other handlers to wear long

- sleeved shirt and long pants, shoes plus socks, and chemical

- resistant gloves.

Occupational Handler Non

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

- cancer exposure and dose for oc cupational 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)

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

- exposure

- data.htmlPage 13 of 23



### Summary of Occupational Handler Non

- Cancer Exposure and Risk Estimates The occupational handler exposure and risk estimates indicate that the short

- and intermediate

term dermal and inhalation combined MOEs are not of concern to HED (i.e., MOE > 100) with
the use of chemical

- resistant gloves as personal protective equipment as directed by th e label

.

At the baseline level of personal protection (i.e., no gloves and no respirator), only one scenario results in a risk estimate below the LOC with a combined (dermal + inhalation) MOE of 8 2 ; this scenario is mixing/loading a liquid formulation for aerial application to high acreage crops. With the addition of gloves, the combined dermal + inhalation MOE is 470 , which is not of concern. All other scenarios result in risk estimates greater t han 220 with baseline attire.

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 cock pits) 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 thi s level of protection, there are no risk estimates of concern for applicators.

The Agency matches quantitative occupational exposure assessment with appropriate characterization of exposure potential. While HED presents quantitative risk estimates for hum an 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 avia tion 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 contin ue to monitor all available information sources to best assess and characterize the exposure potential for human flaggers in agricultural aerial applications.Page 14 of 23

Table 6 .1. 1. Occupational Handler Non

- Cancer Exposure and Risk Estimates for Flutriafol

.

Exposure
Scenario Crop or Target Dermal Unit Exposure
( μ g/lb ai) 1 Inhalation

Unit Exposure
( μ g/lb ai) 1 Maximum

Application
Rate (lb ai/A) 2 Area

Treated (acres) 3 Dermal

(LOC = 1 00) Inhalation
(LOC = 1 00) Total

(LOC =
1 00)

Mitigation
Level Mitigation

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

Mixer/Loader

Aerial application of liquid
formulation Brassica (cole) leafy vegetables,

Celery, Leafy Vegetables, Cucurbits, Pecans (and other tree nuts), Almonds and Walnuts, Peppers (and Other Fruiting Vegetables), Tomatoes, Strawberry 220
(baseline)

0.219

(baseline) 0.114 350 0.0267 280 0.000127 59,000 280

Cotton, Wheat (spring and winter) and Triticale, Sorghum 1200 0.0916 82

0.000435 17,000 82

37.6 (single layer w/gloves) 0.0156 480 470

Groundboom application of liquid formulation Brassica (cole) leafy vegetables,

Celery, Leafy Vegetables, Cucurbits, Pecans (and other tree nuts), Almonds and Walnuts, Peppers (and Other Fruiting Vegetables), Tomatoes, Strawberry 220 (baseline) 0.114 80 0.00612 1,200 0.000029 260,000 1,200

Wheat (spring and winter) and Triticale, Sorghum 200 0.0153 490 0.0000723 100,000 490

Cotton 0.26 200 0.0347 220 0.000165 45,000 220

Airblast application of liquid formulation Pecans (and other tree nuts),

Almonds and Walnuts 0.114 40 0.00304 2,500 0.0000145 520,000 2,500

Applica tor

Aerial spray application Brassica (cole) leafy vegetables,

Celery, Leafy Vegetables, Cucurbits, Pecans (and other tree nuts), Almonds and Walnuts, Peppers (and Other Fruiting 2.08 (engineering control) 0.0049

(engineering control) 0.114 350 0.000253 30,000 0.00000284 2,600,000 30,000Page 15 of 23

Table 6 .1. 1. Occupational Handler Non

- Cancer Exposure and Risk Estimates for Flutriafol

.

Exposure
Scenario Crop or Target Dermal Unit Exposure
( μ g/lb ai) 1 Inhalation

Unit Exposure
( μ g/lb ai) 1 Maximum

Application
Rate (lb ai/A) 2 Area

Treated (acres) 3 Dermal

(LOC = 1 00) Inhalation
(LOC = 1 00) Total

(LOC =
1 00)

Mitigation
Level Mitigation

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

Vegetables), Tomatoes, Strawberry

Cotton, Wheat (spring and winter) and Triticale, Sorghum 1200 0.000867 8,700 0.00000971 770,000 8,600

Groundboo m spray application Brassica (cole) leafy vegetables,

Celery, Leafy Vegetables, Cucurbits, Pecans (and other tree nuts), Almonds and Walnuts, Peppers (and Other Fruiting Vegetables), Tomatoes, Strawberry 78.6
(baseline) 0.34

(baseline) 0.114 80 0.00218 3,400 0.0000449 170,000 3,300

Wheat (spring and winter) and Triticale, Sorghum 0.114 200 0.00545 1,400 0.000112 67,000 1,400

Cotton 0.26 200 0.0124 600 0.000257 29,000 590

Airblast spray application Pecans (and other tree nuts),

Almonds and Walnuts 1770
(baseline) 4.71

(baseline) 0.114 40 0.0246 300 0.000312 24,000 300

Flagger

Flagger for aerial spray application Brassica (cole) leafy vegetables,

Celery, Leafy Vegetables, Cucurbits, Pecans (and other tree nuts), Almonds and Walnuts, Peppers (and Other Fruiting Vegetables), Tomatoes, Strawberry

, Cotton, Wheat (spring and winter) and Triticale,

Sorghum 11
(baseline) 0.35

(baseline) 0.114 350 0.00134 5,600 0.000203 37,000 4,900

Bolded MOEs are below the LOC of 1 00.
1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” ( March 2013 ); Level of mitigation: Baseline, PPE (gloves) , Eng. Controls.
2 Based on proposed label s (Reg. No. 67760

- REN

, 67760

- 75

, 67760

- REA ).
3 Exposure Science Advisory Council Policy #9.1.
4 D ermal Dose = Dermal Unit Exposure ( μ g/lb ai) × Conversion Factor (0.001 mg/ μ g) × Application Rate (lb ai/acre) × Area Treated (A/day) × DAF ( 2 1 %) ÷ BW ( 69 kg).
5 Dermal MOE = Dermal NOAEL ( 7.5 mg/kg/day) ÷ Dermal Dose (mg/kg/day).

6 Inhalation Dose = Inha lation Unit Exposure ( μ g/lb ai) × Conversion Factor (0.001 mg/ μ g) × Application Rate (lb ai/acre) × Area Treated (A / day) ÷ BW ( 69 kg).

7 Inhalation MOE = Inhalation NOAEL ( 7.5 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).Page 16 of 23

8 Total MOE = NOAEL ( 7.5 mg/kg/day) ÷ ( Dermal Dose + Inhalation Dose )

.Page 17 of 23



### 6

. 2 Occupational Post

- application Exposure/ Risk Estimates

HED uses the term post

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

entry 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

- appli cation exposure levels vary over time and depend o n 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 flutriafol at this time primarily because of the low acute inhalation toxicity (Toxicity Category IV) and low vapor pressure ( 3.0 x 10 - 9 

### mmHg, 20°C )

. However, there are multiple potential sources of pos t

- application inhalation exposure to individuals performing post

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



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

- application inhalation exposure data generated by the ARTF and may, as appropriate, develop policies and procedures, to identify the need for and, subsequently, the way to in corporate occupational post

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

- application inhalation exposure assessme nt for flutriafol

.

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 o f pesticides outdoors is likely to result in higher exposure than post

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

- application inhalation exposur e scenarios.

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

- application inhalation

exposure. However, the airblast applicator scenario is be lieved 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.htmlPage 18 of 23



### 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 assessment was not conducted for the soil application of flutriafol to cotton since it is applied at planting when no crop foliage is present. 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 proposed soil

- directed use for cotton , post

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

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

- term and exposures 30 days to six mo nths as intermediate

- term. For flutriafol

, short

- and intermediate

- term exposures
are expec ted 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 7 days apart

. In addition, the short

- and intermediate

- term PODs are the same; therefore, short

- term risk estimates are protective of longer

- term exposures.

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

application exposur e. 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 standar d values recommended for use in predicting post

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

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



### .

For this assessment, post

- application dermal exposu re was assessed for the activity with the highest transfer coefficient for each crop/crop group , and is considered to be protective of all
other activities within that crop/crop group

.

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 (cm 2 /hr ) Activities

Brassica (cole) leafy vegetables, Celery, Leafy Vegetables Vegetable, head and
stem Brassica
and Vegetable, leafy Low/High Min/Full 4,200 Scouting, Hand harvesting, Hand weeding, Topping

Cotton Field / row crop, low /
medium Low Min/Full 210 Scouting

Cucurbits Vegetable, cucurbit Low Min/Full 1,900 Hand

- set Irrigation

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

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

- app

- exposure

- data.htmlPage 19 of 23

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 (cm 2 /hr ) Activities

Pecans (and other tree nuts), Almonds and
Walnuts Tree, "nut" High Full 1,400 Hand harvesting

Peppers (and Other Fruiting Vegetables),

Tomatoes Vegetable, fruiting Low/High Min/Full 1,900 Hand

- set Irrigation

Wheat (spring and winter) and Triticale Field / row crop, low /
medium Low Min/Full 1,100 Scouting

Strawberry Berry, low Low Full 1,100 Hand harvesting

Sorghum Field / row crop, tall Low/High Min/Full 210 Scouting



### 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 N on

- 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 sho rt

- and intermediate

- term post

- application exposure scenarios associated with the proposed uses for flutriafol are summarized in Table 6.2.2.2. All scenarios resulted in MOEs greater than the LOC of 1 00 (ranging from 230 to 4 ,600 ) on day 0 (12 hours after application) and, therefore, are not of concern to HED.

Table 6

. 2 .2.2

. Occupational Post

- application Non

- Cancer Exposure and Risk Estimates for Flutriafol

.

Crop/Site Activities Transfer
Coefficient (cm 2 /hr) Proposed

Application Rate (lb ai/A) DFR 1 Dermal Dose (mg/kg/day) 2 MOE 3

(LOC =
1 00)

Short

- and Intermediate

- term
Brassica (cole) leafy vegetables, Celery, Leafy Vegetables Scouting, Hand

harvesting, Hand weeding, Topping 4,200 0.114 0.32 0.033 230

Cotton Scouting 210 0.002 4,600Page 20 of 23

Table 6

. 2 .2.2

. Occupational Post

- application Non

- Cancer Exposure and Risk Estimates for Flutriafol

.

Crop/Site Activities Transfer
Coefficient (cm 2 /hr) Proposed

Application Rate (lb ai/A) DFR 1 Dermal Dose (mg/kg/day) 2 MOE 3

(LOC =
1 00)

Short

- and Intermediate

- term

Cucurbits Hand

- set Irrigation 1,900 0.015 510

Pecans (and other tree nuts),
Almonds and
Walnuts Hand harvesting 1,400 0.011 690

Peppers (and Other Fruiting Vegetables),

Tomatoes Hand

- set Irrigation 1,900 0.015 510

Wheat (spring and winter) and
Triticale Scouting 1,100 0.009 880

Strawberry Hand harvesting 1,100 0.009 880

Sorghum Scouting 210 0.002 4,600

1 DFR = Application Rate × F × (1

- D) t × 4.54E8 μg/lb × 2.47E

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

. 2 Daily Dermal Dose = [DFR (μg/cm 2 ) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × dermal absorption ( 2 1 %)] BW ( 69 kg).
3 MOE = POD ( 7.5 mg/kg/day) / Daily Dermal Dose.



### 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 n ot 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 21 of 23



### 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:

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:

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 derm al 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:

wher e:

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 AlgorithmsPage 22 of 23



### Po tential daily exposures for occupational post

- application workers are calculated using the following formulas:

where:

DFR t 

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

### ),
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).

where:

E = exposure (mg ai/day),
TC = transfer coefficient (cm 2 

### /hr),

DFR t 

### = dislodgeable foliar residue on day “t” (μg/cm 2 

### ), and

ET = exposure time (hours/day).

The daily doses are calculated using the following formula:

where:

ADD = average daily dose absorbed in a give n 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 i s 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. Al l MOE values are calculated using the following formula:Page 23 of 23



### 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).