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



### Date: 7/23/2013 OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION



### Subject : Fluxapyroxad; Occupational and Residential Expos ur e Assessment for a Proposed Use on a wide range of food and seed commodit i es.

PC Code: 1 3800 9 DP Barcode: 403943, 404520, 404524,

404525

, 404527,404529

, 404532

, 405413

Decision No.: 46 668 6, 4 75980, 466653 Registration No. : 7969-306

, 7969-307

, 7969-308

, 7969-309, 7969-310, 7969-311

, 7969-312

, 7969-GLE, 7969-GUO, 7969-

GLN

Petition No.: 2F8053, 2F8058, & 3F8161 Reeulatory Action: Section 3 Registration

Risk Assessment Type: Si n gle Chemical Aggregate Case No.: 3125

TXRNo.: NA CAS No.: 907204-31-3

MRIDNo.: NA 40 CFR: 180.666



### FROM: James S. Miller, E nvironmental Scientist

# <f~ J{

# ~ Angela Howard, PhD., Toxico l ogist 

# c;::1

Risk Assessment Branch 4**~** Health Effects Division (7509P) 1\

## _/~

# THROUGH:**~a** S. Davis, Acting Chief

# ~(~ _ 

# V

# fJt..~ n'-f1'-<- 

## l

Susan V. Hummel, Branch Senior**~tt""'-** Thurston G. Morton, Chemist

Risk Assessment Branch 4, HED (7509P)



### TO: Olga Odiott, Risk Manager Fungicide Branch Registration Division (7505P)



### Introduction
The Registration Division (RD) requested that the Hea lth Effects Division (HED) con duc t an

exposure an d risk asses sme n t for the proposed new uses of the activ e ingredi ent fluxapyroxad on

a wide range of food and seed commodities. It is HED policy to use the be st ava ilable 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)

Page I of34

### database; the Outdoor Residential Exposure Task Force (ORETF) database; the 

### Agricultural Reen t ry Task Force (ARTF) database; ExpoSAC Policy 14 (SOPs for Seed

T reatment), and the Residential SOPs (section 3 "Lawns and Turf'). Some of these data are proprietary, and subject to the data protection provisions of the Federal Insecticide, Fungicide

, and Rodenticide Act ( F IFRA).

P ag e 2 o f34Page 3 of 34 

### Table of Contents

1.0 Executive Summary

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

2.0 Risk Assessment Conclusions and Recommendations

................................ ........................ 6
2.1 Data Deficiencies and Requirements

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

................................ ................................ ................................ ....... 7
4.0 Use Profile

................................ ................................ ................................ ........................... 9
5.0 Residential Exposure and Risk Estimates

................................ ................................ .......... 13

5.1 Residential Handler Exposure/Risk Estimates

................................ ............................... 14

5.2 Residential Post

- application Exposure/Risk Estimates

................................ .................. 15

5.3 Residential Risk Estimates for Use in Aggregate Assessment

................................ ...... 16

5.4 Spray Drift

................................ ................................ ................................ ...................... 17

5.5 Residential Bystander Post

- Application Inhalation Exposure

................................ ....... 17

6.0 Occupational Exposure and Risk Estimates

................................ ................................ ...... 18

6.1 Occupational Handler Exposure/Risk Estimates

................................ ............................ 18

6.2 Occupational Post

- application Exposure/Risk Estimates

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

6.2.1 Occupational Post

- application Inhalation Exposure/Risk Estimates

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

- cancer Algorithm s

..................... 27Page 4 of 34



### 1.0 Executive Summary

Fluxapyroxad (3

- (difluoromethyl)

- 1

- methyl

- N

- (3′,4′,5′

- trifluoro[1,1′

- biphenyl]

- 2

- yl)

- 1 H

pyrazole

- 4

- carboxamide) is a fungicide belonging to the carboxamide class of chemicals. It is currently registered for use on a wide range of crops to control a broad spectrum of fungal

diseases. Fluxapyroxad is a pyrazole carboxamide. This assessment provides information to support a Section 3 registration for the use of the fungicide fluxapyroxad for seed and foliar uses

on bulb vegetables, leafy vegetables, brassica vegetables, cucurbit vegetables, and root and tuber vegetables (subgroup 1B). Also, f or foliar uses on the caneberry subgroup, bushberry subgroup, small fruit vine climbing subgroup, low growing berry subgroup, turf, tree nuts and sugarcane. In addition, the registrant is amending the tolerance for the stone fruit crop group, and amending

the use on rice. This document addresses the exposures and estimated risk associated with the proposed new and amended uses of fluxapyroxad.

Proposed Use Profile The quantitative Inhalation only exposure/risk assessment developed is based on individuals involved commercial seed treatment (primary handlers), and planting treated seeds (secondary handlers) as well as aerial, flagging, airblast, chemigation, mechanically pressurized handgun, and groundboom applicators as well as residential hand ler applications to turf using a hose

- end

sprayer , a manually pressurized handgun, and a backpack sprayer.

The formulations are Imbrex Xemium Brand Fungicide (7969

- 306, an emulsifiable concentrate (EC) containing 5.96% fluxapyroxad, 0.52 lb ai/gal with application rates ranging from 0.09 to 0.18 lb ai per acre and a PHI range of 0

- 28 days. ); Xemium 2.78 Fungicide ST (7969

- 307, for seed treatment, 28.78% ai , 2.78 lbs ai/gal with application rates ranging from 0.02 to 0.25 lb ai per 100 lb of seed ); Xemium 2.72 Fungicide ST (7969

- 308, for seed treatment, 28.70% ai, 2.72 lbs ai/gal with application rates ranging from 0.02 to 0.25 lb ai per 100 lb of seed); Sercadis Xemium Brand Fungicide (7969

- 309, EC formulation with 26.55% ai, 2.47 lb ai/gal with applicati on rates ranging from 0.09 to 0.18 lb ai per acre and a PHI range of 0

- 28 days ); Merivon Xemium Brand Fungicide (7969

- 310, with f luxapyroxad at 21.26% ai, 2.09 lb ai/gal with application rates ranging from 0.09 to 0.18 lb ai per acre and a PHI range of 0

- 1 4 days )

, and

Priaxor Xemium Brand Fungicide ( 7969

- 311, with f luxapyroxad at 14.33% ai, 1.39 lb ai/gal with application rates ranging from 0.06 to 0.10 lb ai per acre and a PHI range of 0

- 29 days ) ; along with a new product Xemium 703 Fungicide ST (7969

- GLE, for seed treatment, 21.26% ai , 2.09 lbs ai/gal with application rates ranging from 0.01 to 0.08 lb ai per 100 lb of seed ).

In addition, there are two proposed new products for turf use. These products are Xzemplar Fungicide (7969

- GUO, 26.55% ai, 2.47 lb ai/gal with application rates ranging from 0.14 to 0.22 lb ai per acre and a RTI of 14 days ) and Lexicon Intrinsic Fungicide (7969

- GLN, 14.33% ai, 1.39 lb ai/gal with application rates ranging from 0.16 to 0.23 lb ai per acre and a RTI of 14 days ). The pre

- harvest interval (PHI) ranges from 0 day up to 28 days depending on the crop, with a 14 to 28 day RTI for turf and the restricted entry interval (REI) or 12 hours for all crops/labels. The proposed labels allow for applicat ions via aerial, groundboom, chemigation and/or airblast equipment depending on the crop. The proposed labels require occupational handlers to wear the following personal protective equipment (PPE): mixers, loaders, applicators and other handlers (seed tr eatment activities) wear long

- sleeved shirt and long pants, chemicalPage 5 of 34



### resistant gloves, protective eyewear, and shoes plus socks. However, as noted above only inhalation exposure was accessed.

Exposure Profile For the purposed use sites, t here is a potenti al for short

- and intermediate

- term occupational

inhalation exposure to fluxapyroxad during mixing, loading, application, seed treatment (sewing, bagging, and multiple activities), planting activities and post

- application activities, however chronic exposu re is not expected for the proposed use patterns

. Residential handler and incidental oral exposures were assessed for homeowner applications to turf.

Hazard Concerns

The POD for short

- term inhalation exposure [No Observable Adverse Effect Level (N OAEL ) = 9 mg/kg/day] was selected from the 28

- day dietary study in rats based on thyroid effects ( thyroid follicular hypertrophy/hyperplasia)

. The P O D for intermediate

- term inhalation exposure [No Observable Adverse Effect Level (N OAEL ) = 7.3 mg/kg/day] w as selected from a 90

- day dietary study in rats based also on thyroid effects. The POD for short

- term incidental Oral exposure [No Observable Adverse Effect Level (N OAEL ) = 9 mg/kg/day] was selected from a 28 day toxicity study in rats based on changes in thyroid hormones and thyroid follicular hypertrophy/hyperplasia. PODs for short

- and intermediate

- term dermal exposure were not

selected

. No hazards were identified for exposures via the dermal route in a 28

- day dermal toxicity stud y at the limit dose and the dermal absorption study indicates that there is low absorption (8.38%) via the dermal route in rats

. Further, a lthough developmental toxicity was not assessed in the dermal toxicity study, the Agency has low concern for developmental toxicity

for flu xapyroxad. An uncertainty factor of 100x was applied to endpoints selected for all exposure routes (10x for interspecies extrapolation, 10x for intraspecies variation).

Oral studies were extrapolated for assessment of inhalation hazards, since no repeate d

- dose inhalation studies were available. The HASPOC met on January 17, 2013 to discuss the need for a subchronic inhalation study for fluxapyroxad (TXR # 0056561). The decision was made that this requirement could be waived and a subchronic inhalation s tudy is not required. The weight of the evidence used to support this decision included: the low acute inhalation toxicity of fluxapyroxad, the low volatility of fluxapyroxad and the large margin of exposure demonstrated in the exposure assessment.

Fluxapyroxad is classified as “not likely” to be carcinogenic; therefore a quantitative cancer

assessment was not conducted.

Residential Exposure and Risk

Residential Handlers

The residential handler exposure and risk estimates indic ate that short

- term inhalation MOEs are not of concern to HED (i.e., MOEs > 100) .T he inhalation MOEs range from 420 to 280 ,000.

Residential Post

- application

The residential incidental oral , hand to mouth, object to mouth, soil ingestion exposure s and risk

estimates indic at e that short

- term MOEs are not of concern to HED (i.e., MOEs > 100). T hePage 6 of 34



### MOEs range from 2,600 to 1, 2 0 0 ,000. The aggregate MOE is 2,600 and not of concern to HED (i.e., MOEs > 100)

.

Occupational Exposure and Risk Occupational Handlers The occupational handler exposure and risk estimates indicate th at short

- and intermediate

- term
inhalation MOEs are not of concern to HED (i.e., MOEs > 100). The inhalation MOEs range

from 16,000 to 3 30 ,000.

Seed Treatment Seed treatment (primary and secondary handler) oc cupational handler estimates indicate th at
short

- and intermediate

- term inhalation MOEs are not of concern to HED (i.e., MOEs > 100).
The inhalation MOEs range from 1,100 to 8,800,000,000

.

Occupational Post

-

Application Based on the Agency's current pract ices, a quantitative non

- cancer occupational post

- application inhalation exposure assessment was not performed for fluxapyroxad 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 fluxapyroxad. Although a quantitative occupational post

- application inhalat ion exposure assessment was not performed, an occupation inhalation exposure assessment was performed. 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.

Human Studies Review This risk assessment relies in part on data from studies in which adult human sub jects were intentionally exposed to a pesticide or other chemical. These data, which include [studies from PHED 1.1; the AHETF database; the Outdoor Residential Exposure Task Force (ORETF) database; the ARTF database; ExpoSAC Policy 14 (SOPs for Seed Trea tment); the Residential SOPs (list specific SOP); other registrant

- submitted exposure monitoring studies (list MRID); published literature study, etc] , are (1) subject to ethics review pursuant to 40 CFR 26, (2) have received that review, and (3) are compl iant 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

There are no occupational or residential risk estimates of concern associated with the proposed
new uses of fluxapyroxad (i.e., MOEs > 100).

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

- exposure

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

- app

- exposure

- data.htmlPage 7 of 34



### 2.1 Data Deficiencies and Requirements

Turf Transferable Residue (TTR): In accordance with the updated Part 158 data requirements (2007), a TTR study is required for all occupational (e.g., sod farms, golf courses, parks, and recreational areas) or residential turf uses. As part of the recent revision to the Health Effects Division’s 2012 Standard Operating Procedures for Residential Pesticide Exposure Assessment

, HED analyzed all available data and selected new liquid and granular default values for the

fraction of the application rate availa ble for transfer after a turf application (F AR 

### )

. 2 

### These

defaults are 1% for formulations applied as liquids (i.e., emulsifiable concentrates, liquids, wettable powders, dry flowables, etc.) and 0.2% for granular formulations. Of the available TTR

studies submitted to the Agency, the maximum F AR 

### value seen using a liquid product was 6.1 % or 6.1 times higher than the default residue transfer value. The maximum F AR 

### value seen in a TTR study using a granular product was 0.69% or 3.5X the default residue transfer value. Therefore, for both liquid and granular formulations, a calculated MOE of approximately 10 times higher than the level of concern ( e.g ., an MOE > 1,000 if the LOC = 100 ) using the default residue transfer values would provide an adequate m argin of safety for any potentially higher

residues seen in a chemical

- specific TTR study ( Guidance for Requiring/Waiving Turf Transferrable Residue (TTR) and Dislodgeable Foliar Residue (DFR) Studies . 6/7/2012, Exposure Science Advisory Council ). A TTR s tudy is not required for fluxapyroxad at this time

since the [ hand

- to

- mouth] MOE is greater than] 10 times the LOC based on default values for the fraction of application rate available for transfer after a turf application.

Dislodgeable Foliar Residue (D FR): No hazards were identified for exposures via the dermal

route ; therefore no DFR related information was used in this assessment.

3 .0 Hazard Characterization

A NOAEL of 9.0 mg/kg/day was selected for the short

- term inhalation exposure point of departure. This NOAEL was based on a 28 day dietary study in rats (MRID 47923564), where changes in thyroid hormone levels and thyroid follicular hypertrophy/hyperplasia were observed. A NOAEL of 7.3 mg/kg/day was selected for the intermediate

- term inhalation exposure point of departure. This NOAEL was based on a 90 day dietary study in rats (MRID 47923567), where changes in thyroid hormone levels and thyroid follicular hypertrophy/hyperplasia were noted as
well.

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 (i.e. no inhalation absorption factor)

. The occupational LOC for an MOE = 100 is based on the standard uncertainty factors

for intra

- species variation (10X) and inter

- species extrapolation (10X). An FQPA safety factor of 1X was assigned. Fluxapyroxad is characterized as “not likely to be ca rcinogenic to humans”; therefore, cancer risk was not assessed. The acute toxicity and endpoint selections for fluxapyroxad are summarized in Tables 1 and 2, respectively.

2 http://www.epa.gov/pesticides/science/residential

- exposure

- sop.htmlPage 8 of 34



### Fluxapyroxad has low acute oral, dermal, and inhalation toxicity, registering toxicity categories of (III, III, and IV), respectively. Fluxapyroxad is not irritating to the eyes, only slightly irritating to the skin, and not a dermal sensitizer. Table 1 presents a s ummary of the acute

toxici ty information for fluxapyroxad

.

Table 1. Acute Toxicity Profile for Fluxapyroxad

GDLN Study Type MRID Results Tox Category

870.1100 Acute Oral [rat] 47593558 LD 50 >2,000 mg/kg III

870.1200 Acute Dermal [rat] 47593559 LD5 50 > 2,000 mg/kg III

870.1300 Acute Inhalation [rat] 47593560 LC5 50 >5.1 mg/L/ 4 hr IV

870.2400 Acute Eye Irritation

[White New Zealand rabbit] 47593562 Not irritating IV

870.2500 Acute dermal Irritation [rabbit] 47593561 Slight dermal irritant IV

870.2600 Dermal Sensitization [Guinea Pig] 47593562 Not a sensitizer IV



### Table 2 Summary of Toxicological Doses and Endpoints for Fluxapyroxad for Use in
Residential and Occupational Human Health Risk Assessments

Exposure/
Scenario Point of

Departure Uncertainty

Factors Level of

Concern for Risk

Assessment Study and Toxicological Effects

Dermal Short

and
Intermediate

Term No hazard identified 28

- day dermal toxicity study in rats
LOAEL = Not observed

Inhalation
Short

- Term (1

- 30 days) NOAEL= 9

mg/kg/day UF A =10x

UF H =10x Occupational/

Residential LOC
for MOE = 100 28

- day oral toxicity study in rats

LOAEL = 176 mg/kg/day based on changes in thyroid hormones and thyroid follicular hypertrophy/hyperplasia

Inhalation

Intermediate

term (1

- 6 months) NOAEL= 7.3

mg/kg/day UF A =10x

UF H =10x Occupational/

Residential LOC

for MOE = 100 LOAEL = 35.1 mg/kg/day based on thyroid follicular hypertrophy/hyperplasia

Incidental
Oral Short

Term (1

- 30 days) NOAEL= 9

mg/kg/day UF A =10x

UF H =10x Residential LOC

for MOE = 100 28

- day oral toxicity study in rats

LOAEL = 176 mg/kg/day based on changes in thyroid hormones and thyroid follicular hypertrophy/hyperplasiaPage 9 of 34



### Table 2 Summary of Toxicological Doses and Endpoints for Fluxapyroxad for Use in
Residential and Occupational Human Health Risk Assessments

Exposure/
Scenario Point of

Departure Uncertainty

Factors Level of

Concern for Risk

Assessment Study and Toxicological Effects

Cancer (oral, dermal, inhalation) Classification: Not likely to be carcinogenic to humans at doses sufficient to induce liver

and/or thyroid tumors.

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose

- response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sens itivity among members of the human population (intra

- species). MOE = margin of exposure. LOC = level of concern. N/A = not applicable.



### Absorption A dermal absorption factor was not use d for the exposure assessment. Since no inhalation absorption data a re available, toxicity by the inhalation route is considered to be equivalent to the estimated toxicity by the oral route of exposure.

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

effects.

4 .0 Use Profile

Fluxapyroxad belongs to the succunate

- dehydrogenase (SDH) inhibitor class of fungicides. Fluxapyroxad is a fungicide that provides preventive seed and seedling protection from several

seed and soil borne diseases. A summary of the proposed use profile is presented in Tables 3

.Page 10 of 34



### Table 3

. Summary of Directions for Use of Fluxapyroxad

Appl. Timing, Type, and Equip. Formulation Applic. Rate (lb ai/A) (lb ai/100lb seed) for
seed

treatment Max. No.

Applic. per

Season Max.

Seasonal Applic.

Rate (lb ai/A) PHI

(days)

Berries and Small Fruits (inc caneberries, bushberries, strawberries, etc)

Ground,

Aerial or Chemigation 5.96% EC (7969

- 306)

26.55% EC (7969

- 309) 21.26% EC (7969

- 310) 14.33% EC (7969

- 311) 0.18 3 0.54 0 (caneberry, bushberry, low

growing berry)

14 (grape and small
fruit vine climbing subgroup)

Use Directions and Limitations: A minimum 7

- day RTI is specified. Mix Imbrex (7969

- 306), Sercadis (7969

- 309), Merivon (7969

- 310), Priaxor (7969

- 311) with water only for crops in the caneberry and bushberry crop group. Do not make more than 2 sequential applications before alternating to a labeled non

- Group 7 fungicide. Not registered in CA. Brassica Vegetables

Ground,
Aerial or Chemigation 5.96% EC (7969

- 306)

26.55% EC (7969

- 309) 21.26% EC (7969

- 310) 14.33% EC (7969

- 311) 0.09 3 0.27 3

Use Directions and Limitations: A minimum 7

- day RTI is specified. Do not make more than 2 sequential applications before alternating to a labeled non

- Group 7 fungicide. Not registered in

CA.

Seed

Treatment 28.78% SC (7969

- 307)

28.7% SC (7969

- 308) 21.26% (7969

- GLE) 0 .04 0.08 (GLE) Not

applicable Not

applicable Not applicable

Use Directions and Limitations: Rate is expressed in lb ai/100 lb seed. Apply in enough water to ensure adequate coverage, but without damaging the seed. Bulb Vegetables

Ground,

Aerial or Chemigation 5.96% EC (7969

- 306)

26.55% EC (7969

- 309) 21.26% EC (7969

- 310) 14.33% EC (7969

- 311) 0.18 3 0.54 7

Use Directions and Limitations: A minimum 7

- day RTI is specified. Do not make more than 2 sequential applications before alternating to a labeled non

- Group 7 fungicide. Not registered in

CA.

Seed

Treatment 28.78% SC (7969

- 307)

28.7% SC (7969

- 308) 21.26% (7969

- GLE) 0.04 (0.25
for onion smut) 0.08 (GLE) Not

applicable Not

applicable Not applicablePage 11 of 34



### Table 3

. Summary of Directions for Use of Fluxapyroxad

Appl. Timing, Type, and Equip. Formulation Applic. Rate (lb ai/A) (lb ai/100lb seed) for
seed

treatment Max. No.

Applic. per

Season Max.

Seasonal Applic.

Rate (lb ai/A) PHI

(days)

Use Directions and Limitations: Rate is expressed in lb ai/100 lb seed. Apply in enough water to ensure adequate coverage, but without damaging the seed. Cucurbit Vegetables

Ground,
Aerial or Chemigation 5.96% EC (7969

- 306)

26.55% EC (7969

- 309)
21.26% EC (7969

- 310) 14.33% EC (7969

- 311) 0.09 3 0.27 0

Use Directions and Limitations: A minimum 7

- day RTI is specified. Mix Imbrex (7969

- 306), Sercadis (7969

- 309), Merivon (7969

- 310), Priaxor (7969

- 311) with water only. Do not make more than 2 sequential applications before alternating to a labeled non

- Group 7 fungicide. Not registered in CA.

Seed

Treatment 28.78% SC (7969

- 307)

28.7% SC (7969

- 308) 21.26% (7969

- GLE) 0.04 0.06 (GLE) Not

applicable Not

applicable Not applicable

Use Directions and Limitations: Rate is expressed in lb ai/100 lb seed. Apply in enough water to ensure adequate coverage, but without damaging the seed. Grapes

Ground,
Aerial or Chemigation 5.96% EC (7969

- 306)

26.55% EC (7969

- 309) 21.26% EC (7969

- 310) 14.33% EC (7969

- 311) 0.09 (0.18) 6 (3) 0.54 14

Use Directions and Limitations: A minimum 10

- day RTI is specified. The safety of all possible tank mixtures with Imbrex (7969

- 306), Sercadis (7969

- 309), Merivon (7969

- 310), Priaxor (7969

- 311) has not been tested. Safety should be confirmed prior to application. Do not make more than 2 sequential applications before alternating to a labeled non

- Group 7 fungicide. Not registered in CA. Leafy Vegetables

Ground,
Aerial or Chemigation 5.96% EC (7969

- 306)

26.55% EC (7969

- 309) 21.26% EC (7969

- 310) 14.33% EC (7969

- 311) 0.18 3 0.54 1

Use Directions and Limitations: A minimum 7

- day RTI is specified. Do not apply Imbrex, Sercadis, Merivon, Priaxor to spinach as a tank mix. The safety of all possible tank mixtures with Imbrex (7969

- 306), Sercadis (7969

- 309), Merivon (7969

- 310), Priaxor (7969

- 311) has not been tested on leafy vegetables. Safety should be confirmed prior to application. Do n ot make more than 2 sequential applications before alternating to a labeled non

- Group 7 fungicide. Not registered in CA except for lettuce drop on leaf and head lettuce.

Seed

Treatment 28.78% SC (7969

- 307)

28.7% SC (7969

- 308) 21.26% (7969

- GLE) 0.04

- 2 dep ending on target disease 0.06 (GLE) Not

applicable Not

applicable Not applicablePage 12 of 34



### Table 3

. Summary of Directions for Use of Fluxapyroxad

Appl. Timing, Type, and Equip. Formulation Applic. Rate (lb ai/A) (lb ai/100lb seed) for
seed

treatment Max. No.

Applic. per

Season Max.

Seasonal Applic.

Rate (lb ai/A) PHI

(days)

Use Directions and Limitations: Rate is expressed in lb ai/100 lb seed. Apply in enough water to ensure adequate coverage, but without damaging the seed.

Rice

Ground,

Aerial or Chemigation 5.96% EC (7969

- 306)

26.55% EC (7969

- 309) 0.13 2 0.27 28

Use Directions and Limitations: A minimum 7

- day RTI is specified. Do not make more than 2 sequential applications before alternating to a labeled non

- Group 7 fungicide. Not registered in

CA.

Seed

Treatment 28.78% SC (7969

- 307)

28.7% SC (7969

- 308) 0.05 Not applicable Not

applicable Not applicable

Use Directions and Limitations: Rate is expressed in lb ai/100 lb seed. Apply in enough water

to ensure adequate coverage, but without damaging the seed.

Root Vegetables Crop Subgroup 1B

Ground,
Aerial or Chemigation 5.96% EC (7969

- 306)

26.55% EC (7969

- 309) 21.26% EC (7969

- 310) 14.33% EC (7969

- 311) 0.09 3 0.27 7

Use Directions and Limitations: A minimum 7

- day RTI is specified. Do not make more than 2 sequential applications before alternating to a labeled non

- Group 7 fungicide. Not registered in

CA.

Seed

Treatment 28.7% SC (7969

- 308)

21.26% (7969

- GLE) 0.04 0.06 (GLE) Not

applicable Not

applicable Not applicable

Use Directions and Limitations: Rate is expressed in lb ai/100 lb seed. Apply in enough water to ensure adequate coverage, but without damaging the seed. Sugarcane

Ground,

Aerial or Chemigation 5.96% EC (7969

- 306)

26.55% EC (7969

- 309) 14.33% EC (7969

- 311) 0.11 2 0.22 14

Use Directions and Limitations: A minimum 7

- day RTI is specified. Do not make more than 2 sequential applications before alternating to a labeled non

- Group 7 fungicide. Not registered in

CA.

Tree Nuts

Ground,
Aerial or Chemigation 5.96% EC (7969

- 306)

26.55% EC (7969

- 309) 21.26% EC (7969

- 310) 14.33% EC (7969

- 311) 0.11 3 0.33 14

Use Directions and Limitations: A minimum 7

- day RTI is specified except for pistachio which has an RTI of 10 days. Do not make more than 2 sequential applications before alternating to a

labeled non

- Group 7 fungicide. For aerial do not use less than 10 gallons of spray solution per acre. Not registered in CA.Page 13 of 34



### Table 3

. Summary of Directions for Use of Fluxapyroxad

Appl. Timing, Type, and Equip. Formulation Applic. Rate (lb ai/A) (lb ai/100lb seed) for
seed

treatment Max. No.

Applic. per

Season Max.

Seasonal Applic.

Rate (lb ai/A) PHI

(days)

Turf

Ground, Aerial, Chemigation,
and/or Mechanically

Pressurized
Hand Gun 26.55% SC (7969

- GUO)

14.33% SC (7969

- GLN) 0.23 N/A 0.80 N/A

Use Directions and Limitations: A 14

- 28 day RTI is specified for turf applications. Do not make more 2 sequential applications in the Fall and Spring, or more than 0.80 lbs ai/Acre per Acre per season. Do not make more than 2 sequential applications bef ore alternating to a

labeled non

- Group 7 fungicide. Aerial applications are to be conducted for Sod farms only with

a 100 ft. buffer in the State of NY.
1. The restricted entry interval (REI) is 12 hours for all crops/labels



### 5 .0 Residential Exposure an d Risk Estimates

The proposed uses are expected to result in residential exposure : therefore, a quantitative

residen tial exposure assessment was conducted. A summary of the proposed use profile is presented in Table 4.

Table 4. Short

- Term Residential Handler Exposure and Risk Estimates for Fluxapyroxad.

Exposure
Scenario Target

MOE Inhl. Unit Exposure (ug/lb ai) Maximum

Application Rate a 

### (lb ai/gal)

Or (lb ai/Acre) Area

Treated b 

### Inhalation

Dose (mg/kg/day) c 

### MOE d



### Mixer/loader/Applicator (Turf

- Lawns)

Hose

- end Sprayer/

100 0.022 0.23 0.5 Acres 0.000032 280,000

Manually

Pressurized
Handwand 0.018

2.47 5 Acres 0.0028 3,200

Backpack Sprayer 0.14 0.022 420

Based on regi stered or proposed label (0.023 lb ai/A) and (2.47 lb ai/gal) : Exposure Science Advisory Council Policy #9.1. Inhalation Dose = Inhalation Unit Exposure (ug/lb ai) x Conversion Factor (0.001 mg/ug) x Application Rate (lb ai/acre or gal ) x Area Tr eated or

Amount Handled (A or gallons/day) / BW (kg). Inhalation MOE = Inhalation NOAEL (mg/kg/day) / Inhalation Dose (mg/kg/day).Page 14 of 34



### 5 .1 Residential Handler Exposure/Risk Estimates

HED uses the term “handlers” to describe those individuals who are involved in the pesticide application process. HED beli eves that there are distinct tasks related to applications and that exposures can vary depending on the specifics of each task. Residential handlers are addressed somewhat differently by HED as homeowners are assumed to complete all elements of an applica tion without use of any protective equipment.

The quantitative exposure/risk assessment developed for residential handlers is based on the following scenarios:

1. Open mixing/loading/applying for a hose

- end sprayer application to turf (homeowner lawns);

2. Open mixing/loading/applying for a manually pressurized handgun. application to turf (homeowner lawns);

3. Open mixing/loading/applying for a backpack sprayer application to turf (homeowner lawns).

Residential Handler Exposure Data and Assumptions

A series of assumptions and exposure factors served as the basis for completing the residen tial

handler risk assessments. E ach assumption and factor is detailed below.

Application Rate : See table 4 for specifics.

Unit Exposures and Area Treated or Amount Handled : Unit exposure values and estimates for area treated or amount handled were taken from HED’s

2012 Residential SOPs 3



### . See table 4 for specifics.

Exposure Duration: Residential handler exposure is expected to be short

- term in duration. Intermediate

- term exposures are not likely because of the intermittent nature of applications by homeowners ; however, there are some instances where longer

- term exposures are possible (e.g., pet care uses)

.

Residential Handler Non

- Cancer Exposure and Risk Estimate Equations The algorithms used to estimate exposure and dose for residential handlers can be found in Appendix A and/or the 2012 Residential SOPs 4



### .

Summary of Residential Handler Non

- Cancer Exposure and Risk Estimates Fluxapyroxad does not pose a dermal ri sk; therefore, only inhalation exposures for handlers were

calculated. For all residential handler exposure scenarios, inhalation MOEs exceed HED’s LOC ( inhalation LOC = 100), and therefore not of concern to HED (i.e., MOEs > 100). See table 4 for specif ics.

3 Available: http://www.epa.gov/pesticides/science/residenti al

- exposure

- sop.html

4 Available: http://www.epa.gov/pesticides/science/residential

- exposure

- sop.htmlPage 15 of 34



### 5 .2 Residential Post

- application Exposure/Risk Estimates

There is the potential for post

- application exposure for individuals exposed as a result of being in an environment that has been previously treated with fluxapyroxad

. The quantitative exposure/risk assessment for residential post

- application exposures is based on the following

scenarios:

1. Hand to Mouth

2. Object to Mouth

3. Incidental Soil Ingestion

The lifestages selected for each post

- application scenario are based on an analysis provided as an Appendix in the 2012 Residential SOPs 5 

### . These lifestages are not the only lifestages that could be potentially exposed for these post

- application scenarios; however, the assessment of these lifestages is health protective for the e xposures and risk estimates for any other potentially exposed lifestages.

Residential Post

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

- application risk asse ssment . Each assumption and factor is detailed in the 2012 Residential

SOPs 5



### .

Residential Post

- application Non

- Cancer Exposure and Risk Equations The algorithms used to estimate residential post

- application exposure and dose can be found in Appendix A and/or the 2012 Residential SOPs 5



### .

Summary of Residential Post

- application Non

- Cancer Exposure and Risk Estimates Residential estimated risks far exceed the level of concern (LOC) of 100, and are, therefore, not

of concern. A summary of the residential post

- application exposures and risks are provided
below in Table 5.

Table 5. Residential Post

- application Non

- cancer Exposure and Risk Estimates for Fluzapyroxad.

Lifestage Post

- application Exposure Scenario Application

Rat e 1
(lb ai/acre) Dose

(mg/kg/day) 2 MOEs 3 Use Site Route of Exposure

Adult

Turf/Lawns Inhalation N/A: no dermal endpoint

Child Hand to Mouth

0.23 0.0035 2,600

Object to Mouth 0.00011 85,000

Incidental Soil Ingestion 0.0000078 1,200,000

1. Based on registered or proposed label (Reg. No. 7969

- GUO, 7969

- GLN ).

2. Dose (mg/kg/day) equations: HtM: E = [HR * ( F M * SA H ) * (ET * N_Replen) * (1

- (1

- SE ) (Freq_HtM/N

- Replen) /BW )] . OtM: E = [OR* CF1 * SAM O * (ET * N_Replen) * (1

- (1

- SE O ) (Freq_OtM/N_Rep len) /BW )] . ISI: E = [OR* CF1 * SAM O * (ET * N_Replen) * (1

- (1

- SE O ) (Freq_OtM/N_Replen) ) /BW ]
3. MOE = POD (mg/kg/day) ÷ Dose (mg/kg/day).

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

- exposure

- sop.htmlPage 16 of 34



### It is noted that the 0.23 lb ai /acre application rate for turf was modeled to estimate post

application residential exposure of children. As this rate is equal to or higher than many of agricultural application rates, this scenario is protective of any exposure of farm children via

spr ay drift from agricultural fluxapyroxad applications.

5

. 3 Residential Risk Estimates for Use in Aggregate Assessment

The recommended residential exposure for use in the children 1<2 years old aggreg ate
assessment reflects hand

- to

- mouth e xposures from children playing on turf. The residential doses

to be used fo r the aggregate risk assessment and the source of those exposures are shown in
Table 6 , below.

1. Bolded risk estimates should contribute to the residential exposure portion of the aggregate assessment.

2. Residential Handler Dose = the highest handler dose for each applicable lifestage of all s cenarios assessed from Table 5

. 3. Residential Handler MOE = the MOEs associated with the high est doses identified in Table 5

. 4. Residential Post

- application Dose = the highest post

- application dose for each applicable lifestage of all scenarios assessed from Table 6

. 5. Residential Post

- application MOE = the MOEs associated with the high est doses identified in Table 6

6. Lifestage population was combined (BW = 80) due to an inhalation only assessment with MOEs well above 100.

7. For aggregate exposure, HtM will be used, whereas this scenario is the most conservative.



### There are no residential use scenarios that would result in potential intermediate

- term exposure to fluxapyroxad ; therefore, an intermediate

- term aggregate risk assessm ent is not required. Table 6. Recommendations for the Short

- and Intermediate

- Term Residential Exposures for the Fluxapyroxad Aggregate Assessment 1

Lifestage Handler Exposure

(mg/kg/day) 2 Residential

Handler Total Exposure (mg/kg/day) 3 Residential

Handler

Total MOE 4 Post

- application Exposure

(mg/kg/day) 5 Residential

Post

- application Total Exposure (mg/kg/day) Residential

Post

application

MOE 6 

### Dermal Inhalation Dermal Inhalation Oral

Short

- Term

Adult

Male N/A 0.022 0.022 420 N/A N/A N/A N/A N/A

Adult

Female N/A 0.022 0.022 420 N/A N/A N/A N/A N/A

Child N/A N/A N/A N/A N/A N/A 0.0035 0.0035 2600

Intermediate

- Term

Adult

Male

N/A N/A Adult

Female

ChildPage 17 of 34



### 5

. 4 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 ground application metho d employed for [chemical] . 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 (see the Agency’s Spray Dr ift website for more information 6



### . 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 A gDRIFT 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 may impose further refinements in spray drift management practices to reduce

off

- target dr ift with specific products with significant risk estimates associated with drift.

Although a quantitative residential post

- application inhalation exposure assessment was not performed as a result of pesticide drift from neighboring treated agricultural fi elds, an inhalation exposure assessment was performed for flaggers. This exposure scenario is representative of a worse case inhalation (drift) exposure and may be considered protective of most outdoor agricultural and commercial post

- application inhalati on exposure scenarios

.

It is noted that the 0.23 lb ai/acre application rate for turf was modeled to estimate post

application residential exposure of children. As this rate is equal to or higher than many of agricultural application rates, this scenario is protective of any exposure of farm children vi a spray drift from agricultural fluxapyroxad applications.

5

. 5 Residential Bystander Post

- Application Inhalation Exposure

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

- application i nhalation exposure assessment was not performed for fluxapyroxad at this time primarily because of the low acute inhalation toxicity (Toxicity Category III and IV), low vapor pressure (insert VP), and the low proposed use rate (0.xx lb ai/A). However, vol atilization 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, Fungi cide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 7



### . The Agency is in the process of evaluating the SAP report and may, as appropriate, develop policies and procedures to identi fy the need for and, subsequently, the way to incorporate post

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

- application inhalation exposure assessment for

flu x apyroxad

.

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

7 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.htmlPage 18 of 34



### 6 .0 Occupational Exposure and Risk Estimates

6 .1 Occupational Handler Exposure/Risk Estimates

Occupational handler and post

- application exposure scenarios were assessed to support proposed

crop , turf, and seed treatment uses . Based on the product labels and information provided by the registrant, short

- and intermediate

- term exposure is assessed for occupational handlers and post

application activities. Chronic exposure is not expected for the proposed use pa tterns. Only inhalation exposures are assessed for proposed new uses of fluxapyroxad. Dermal exposures are
not assessed because PODs for short

- and intermediate

- term dermal exposure were not selected because fluxapyroxad does not pose a de rmal hazard

. L abels for fluxapyroxad formulations require that mixers, loaders, applicators and other handlers (seed treatment activities) wear long

sleeved shirt and long pants, chemical resistant gloves, protective eyewear, and shoes plus socks.

The quantitative exp osure/risk assessment developed for occupational handlers is based on the following scenarios:

Mixing and Loading Scenarios

• Open mixing/loading for aerial application;

• Open mixing/loading for groundboom application;

• Open mixing/loading for airbl ast application.

• Open mixing/loading for chemigation application.

Application Scenarios • Applying sprays with aerial equipment; • Applying sprays with groundboom equipment; • Applying sprays with airblast equipment ;

Mixing/Loading/Applying Scenarios

• Open mixing/loading /applying for manually pressurized handgun application

.

Flagging : Flagging for liquid aerial applications

Seed Treatment ( Primary Handler

– Treating Seed) Mixing, loading, applying liquid formulations; Bagging treated seed; Sewing bags; and Multiple activities

(Secondary Handler

– Planting Seed) Planting treated seed consists of the farmer purchasing bags of treated seed, placing the seed in the hopper and applying seed to fields

.Page 19 of 34



### Occupational Handler Exposure Data a nd 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 :

• Maximum label application rates for aerial, groundboom , chemigation and airblast:

0.09

– 0.23 lb ai/A

• Maximum label application rates for mechanically pressurized handgun:

1.39

– 2.47 lb ai/gal

• Maximum label application rates for seed treatment:
0.01

- 0.2 5 lb ai/100 lb seed

Area Treated or Amount Handled:

• Area treated for aerial, groundboom and airblast application: 1200 acres per day for aerial application to high acreage field crops 350 acres per day for aerial application t o typical field crops, grapes, and sod 350 acres per day for chemigation application to typical field crops 80 acres per day for groundboom application to sod and typical field crops 4 0 acres per day for groundboom application to turf (golf course)

4 0 acres per day for air blast application to orchards (tree nuts/grapes) 5 acres per day for groundboom application to turf (golf course tees and greens only) 5 acres per day for mechanically pressurized handgun application to turf (parks, athletic fields, commercial areas)

• Amount (pounds) of Seed Treated per Day (Primary Handler)

- Brassica vegetables

– 3, 000

- Bulb vegetables

- 3 ,000

- Cucurbit vegetables

- 339,5 000

- Leafy vegetables

– 3 ,000

- Rapeseed

– 125 ,000

- Rice

– 302,5 00

- Root/tuber vegetab les

– 800 ,000)

• Amount (pounds ) of Seed Planted per Day (Secondary Handler)

- Brassica vegetables

– 112.45

- Bulb vegetables

- 756.88

- Cucurbit vegetables

- 614.60

- Leafy vegetables

– 4.84

- Rapeseed

– 60,550

- Rice

– 17,424

- Root/tuber vegetables

– 418.18

Amount of Seed Planted Per Day: The amount of seed planted per day is based on information provided in the HED Reviewer’s Aid to Calculating Occupational Exposures from Activities Related to Agricultural Seed Treatment (November 29, 2012) and the BEAD Acres Plan ted per Day and Seeding Rates of Crops Grown in the United States,Page 20 of 34



### Seed treatment exposure duration: Treatment of the proposed seeds is expected to result in short

- and intermediate

- term exposure.

On

- Farm seed treatment exposure and r isk

HED assumes that the commercial seed treatment risk assessment is protective of on

- farm seed

treatment because the commercial and farm equipment are similar but the on

- farm throughput is significantly less than in commercial seed treatment

.

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

- term and exposures 30 days to six months

as intermediate

- term.

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 sur rogate data in the absence of chemical

- specific 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 protection provisions of FIFRA. The standard values recommended for use in predicting handler exposure that are used in this assessment, known as “unit exposures”, are outlined in the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table 8 

### ”, 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 website 9



### .

Absorption A dermal absorption factor was not use d for the exposure assessment. Since no inhalation absorption data are available, toxicity by the inhalation route is considered to be equivalent to the estimated toxicity by the oral route of exposure.

Body Weight The standard body weight for the ge neral population (80 kg) was used for all exposure scenarios covered in this risk assessment since the endpoints selected were not developmental and/or fetal

effects.

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.

Summary of Occupational Handler Non

- Cancer Exposure and Risk Estimates HED is not concerned with inhalation margins of exposure (MOEs) which are not less than the level of concern (LOC) of 100. All worker exposures are assessed as short

- and intermediate

term based on label prescribed uses and expected exposure durations. Exposure and risk

estimates indicate non

- cancer risks are not of concern for occupational handler activities for the

8 Available: http://www.epa.gov/opp0000 1/science/handler

- exposure

- table.pdf

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

- exposure

- data.htmlPage 21 of 34



### proposed new uses (MOEs > 100). Summaries of occupational handler exposure and risk calculations, assumptions, and results are provided in Tables 7, and 8

.

Table 7 : Short and Intermediate

- Term Risk Assessment For Agricultural Uses of Fluxapyroxad

Exposure
Scenario Inhalation

Unit
Exposure
(μg/lb ai) 1 Crops Application

Rate
(lb ai/A) 2 Area

Treated
(A/day) 3 MOE 4

Short

- Term Intermed

- Term

Inhalation

Mixer/Loader

Aerial
Fixed Wing
(enclosed cockpit) 0.219 Turf (sod farms, golf courses, commercial lawns, parks, rec. areas, cemeteries) 0.23

350 41,000 33,000

Vegetables:

Berries and small fruits, Bulb, Leafy (except Brasica),
Strawberries 0.18 52,000 42,000

Vegetables:
Brassica leafy, Cucurbit, Grapes, Root and tuber (except sugar beet). Sorghum and
Millet 0.09

1200 30,000 25,000

Rice 0.135 20,000 16,000

Groundboom (open Cab)

0.219 Sod

0.23 80 180,000 140,000

Turf (sod farms, golf courses,

commercial lawns, parks, rec. areas, cemeteries) 40 360,000 290,000

Vegetables:

Berries and small fruits, Bulb, Leafy (except Brasica), grapes,
and Strawberries 0.18 80 230,000 190,000

Sorghum and Millet 0.09 200 180,000 150,000

Airblast
(open cab) Orchard
(Tree Nuts) 0.11 40 70,000 600,000

Chemigation Turf (sod farms, golf courses, commercial lawns, parks, rec. areas, cemeteries) 0.23 350 41,000 33,000Page 22 of 34 

### Table 7 : Short and Intermediate

- Term Risk Assessment For Agricultural Uses of Fluxapyroxad

Exposure
Scenario Inhalation

Unit
Exposure
(μg/lb ai) 1 Crops Application

Rate
(lb ai/A) 2 Area

Treated
(A/day) 3 MOE 4

Short

- Term Intermed

- Term

Inhalation

Vegetables:

Berries and small fruits, Bulb, Leafy (except Brasica), Strawberries and Grapes 0.18 52,000 42,000

Sorghum and Millet 0.09 1200 30,000 25,000

Applying

Aerial
Fixed Wing
(enclosed cockpit) 5 0.34 Turf (sod farms, golf courses, commercial lawns, parks, rec. areas, cemeteries) 0.23

350 Exposure estimates are expected to be protected by mixer/loader, whereas application is conducted mechanically while the pilot
in inside the aircraft. Vegetables:

Berries and small fruits, Bulb, Leafy (except Brasica),
Strawberries 0.18 Vegetables:
Brassica leafy, Cucurbit, Grapes, Root and tuber (except sugar beet).

Sorghum and Millet 0.09 1200

Rice 0.135

Groundboom (open Cab) 0.034 Turf (sod farms, golf courses "fairways", commercial lawns, parks, rec. areas, cemeteries). 0.23

80 110,000 93,000

Vegetables:

Berries and small fruits, Bulb, Leafy (except Brasica), Strawberries,
Brassica leafy, Cucurbit, Grapes, Root and tuber (except sugar beet). 0.18 150,000 120,000

Sorghum and Millet 0.09 200 36,000 29,000Page 23 of 34 

### Table 7 : Short and Intermediate

- Term Risk Assessment For Agricultural Uses of Fluxapyroxad

Exposure
Scenario Inhalation

Unit
Exposure
(μg/lb ai) 1 Crops Application

Rate
(lb ai/A) 2 Area

Treated
(A/day) 3 MOE 4

Short

- Term Intermed

- Term

Inhalation

Airblast
(open cab)

(Chemigation) 5 4.71 Orchard
(Grapes and Tree Nuts) 0.18 200 21,000 17,000

Mixing/Loading/Applying

Mechanically

Pressurized Handgun 1.9 Turf (sod farms, golf courses "fairways", commercial lawns, parks, rec. areas, cemeteries). 0.23 5 330,000 270,000

Flagging

Aerial
Fixed Wing
(enclosed cockpit) 0.35 Sorghum and Millit 6 0.09 1200 19,000 15,000

1 Inhalation unit exposure values represent no respirator.

2 Application rates are based on maximum values found in proposed labels

3 Daily area treated is based on the area that can be reasonably applied in a single day for each exp osure scenario of concern based on the application

method and formulation/packaging type. (standard EPA/OPP/HED values).

4 Short

- /Intermediate

- Term MOE = Inhalation NOAEL ( 9.0 mg/kg/day or 7.3 mg/kg/day ) / Daily Inhalation Dose). The LOC is 100.

5 Aeri al and Chemigation: Groundboom applicator MOEs are protective, whereas areal and chemigation application is done mechanically

. 6 So rghum, and Millit have the most conservative MOEs, therefore representative for Flagging activities. * Daily Dose (mg/kg/day) was calculated by Unit Exposure * 100 % Inhalation a bsorption factor * Appl ication rate * Area treated} / 8 0 kg. {Where: inhalation absorption is assumed to be 100 %}



### Seed treatment (primary and secondary handler) occupational handler estimates are summ arized
below.

Table 8. Short

- and Intermediate

- Term Primary and Secondary Handler Exposures and Risks for Fluxapyroxad
Seed Treatment

Seed Type Inhal

UE a mg/lb Max App Rate b

lb ai/lb seed Amt Treated c

lb seed/day Inhal Dose d

mg/kg/day Short

- Term

Inhal MOE e Intermediate

- Term

Inhal MOE f



### Loader/Applicator (No Respirator)

Brassica Vegetables 0.00034 0.0004 3,000 0.0000051 1,800,000 1,400,000

Bulb Vegetables 0.00034 0.0025 3,000 0.000032 280,000 230,000

Cucurbit Vegetables 0.00034 0.0004 339,500 0.00058 16,000 13,000

Leafy Vegetables 0.00034 0.0004 3,000 0.0000051 1,800,000 1,400,000 Rapeseed 0.00034 0.0002 125,000 0.00011 85,000 69,000Page 24 of 34 Table 8. Short

- and Intermediate

- Term Primary and Secondary Handler Exposures and Risks for Fluxapyroxad
Seed Treatment

Seed Type Inhal

UE a mg/lb Max App Rate b

lb ai/lb seed Amt Treated c

lb seed/day Inhal Dose d

mg/kg/day Short

- Term

Inhal MOE e Intermediate

- Term

Inhal MOE f

Rice 0.00034 0.0005 302,500 0.00064 14,000 11,000

Root and Tuber 0.00034 0.0004 800,000 0.0014 6,600 5,400 Sewer (No Respirator)

Brassica Vegetables 0.00023 0.0004 3,000 0.0000035 2,600,000 2,100,000

Bulb Vegetables 0.00023 0.0025 3,000 0.000022 420,000 340,000

Cucurbit Vegetables 0.00023 0.0004 339,500 0.00039 23,000 19,000

Leafy Vegetables 0.00023 0.0004 3,000 0.0000035 2,600,000 2,100,000 Rapeseed 0.00023 0.0002 125,000 0.000072 130,000 100,000

Rice 0.00023 0.0005 302,500 0.00043 21,000 17,000

Root and Tuber 0.00023 0.0004 800,000 0.00092 9,800 7,900 Bagger (No Respirator)

Brassica Vegetables 0.00016 0.0004 3,000 0.0000024 3,800,000 3,000,000

Bulb Vegetables 0.00016 0.0025 3,000 0.000015 600,000 490,000

Cucurbit Vegetables 0.00016 0.0004 339,500 0.00027 33,000 27,000

Leafy Vegetables 0.00016 0.0004 3,000 0.0000024 3,800,000 3,000,000 Rapeseed 0.00016 0.0002 125,000 0.00005 180,000 150,000

Rice 0.00016 0.0005 302,500 0.0003 30,000 24,000

Root and Tuber 0.00016 0.0004 800,000 0.00064 14,000 11,000 Multiple Activities (No Respirator)

Brassica Vegetables 0.0016 0.0004 3,000 0.000024 380,000 300,000

Bulb Vegetables 0.0016 0.0025 3,000 0.0015 60,000 49,000

Cucurbit Vegetables 0.0016 0.0004 339,500 0.0027 3,300 2,700

Leafy Vegetables 0.0016 0.0004 3,000 0.000024 380,000 300,000 Rapeseed 0.0016 0.0002 125,000 0.0005 18,000 15,000

Rice 0.0005 302,500 0.003 3,000 2,400

Root and Tuber 0.0016 0.0004 800,000 0.0064 1,400 1,100

Planters

Brassica Vegetables 0.0034 0.0004 112.45 0.000000024 56,000,000 45,000,000

Bulb Vegetables 0.0034 0.0025 756.88 0.000001 60,000,000 49,000

Cucurbit Vegetables 0.0034 0.0004 614.60 0.00000013 69,000,000 56,000,000

Leafy Vegetables 0.0034 0.0004 4.84 0.000000001 8,800,000,000 7,100,000,000 Rapeseed 0.0034 0.0002 60,550 0.000016 560,000 450,000

Rice 0.0005 17,424 0.0000019 4,900,000 3,900,000Page 25 of 34 Table 8. Short

- and Intermediate

- Term Primary and Secondary Handler Exposures and Risks for Fluxapyroxad
Seed Treatment

Seed Type Inhal

UE a mg/lb Max App Rate b

lb ai/lb seed Amt Treated c

lb seed/day Inhal Dose d

mg/kg/day Short

- Term

Inhal MOE e Intermediate

- Term

Inhal MOE f

Root and Tuber 0.0034 0.0004 418.18 0.000000089 100,000,000 82,000,000

a Unit Exposures from HED Exposure Science Advisory Council Policy 14: Standard Operating Procedures for Seed Treatment.
b Application Rates based on proposed label uses for fluxapyroxad

.

c HED default for lb seed planted per day from HED Exposure Science Advisory Council Policy 15, and Acres planted per day and seeding rates of crops grown in the United States (3/24/2011)
d Daily Inhalation Dose (mg/kg/day) = daily inhalation unit exposure (mg/ lb ai) x application rate (lb ai/lb seed) x amount planted (lb seed/day) x absorption factor (100%) / body weight (8 0 kg adult).

e Short

- term Inhalation MOE = NOAEL (9.0 mg/kg/day for short

- term exposure) / Inhalation Dose (mg/kg/day). Level of concern =

100.

f Intermediate

- term Inhalation MOE = NOAEL (7.3 mg/kg/day for intermediate

- term exposure) / Inhalation Dose (mg/kg/day). Level
of concern = 100.



### The Agency matches quantitativ e occupational exposure assessment with appropriate characterization of exposure potential. While HED presents quantitative risk estimates for human flaggers where appropriate, agricultural aviation has changed dramatically over the past two

decades. Accor ding the 2012 National Agricultural Aviation Association (NAAA) survey of their membership, the use of GPS for swath guidance in agricultural aviation has grown steadily from the mid 1990’s. Over the same time period, the use of human flaggers for aerial p esticide applications has decreased steadily from ~15% in the late 1990’s to only 1% in the most recent (2012) NAAA survey. The Agency will continue to monitor all available information sources to best assess and characterize the exposure potential for hum an flaggers in agricultural aerial applications.

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

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

6

. 2 Occupational Post

- application Exposure/ Risk Estimates

Occupational post

- application dermal exposure was not assessed for fluxapyroxad

, since fluxapyroxa d does not pose a dermal risk. Based on the Agency's current practices, a quantitative occupational post

- application inhalation exposure assessment was not performed for fluxapyroxad at this time . However, an inhalation exposure assessment was performed for occupational handlers and this assessment resulted in risk estimates that did not exceed HED’s

level of concern at baseline inhalation PPE. Since h andler exposure resulting from application of pesticides outdoors is likely to result in higher exposure than post

- application exposure ; these

handler inhalation exposure estimates would be protective of most occupational post

- application inhalation exposure scenarios.

The potential for post

- application exposures following the planting of fluxapyroxad

- trea ted seeds is unlikely because sustained levels of contact with treated seed after it has been placed in thePage 26 of 34



### soil or other planting media would not be expected because no routine cultural practice required for the production of agricultural commodities invo lves 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.

6

. 2 .1 Occupational P ost

- application Inhalation Exposure/Risk Estimates

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

- application inhalation exposure assessment was not performed for fluxapyroxad at this time primarily because of the low acute

inhalation toxici ty (Toxicity Category III and IV), low vapor pressure (insert VP), and the low proposed use rate . However, there are multiple potential sources of post

- application inhalation exposure to individuals performing post

- application activities in previously tre ated 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 10



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

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

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

- application inhalation exposure assessment for fluxapyroxad

.

A post

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

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

- application inhalation exposure scenarios.

Restricted Entry Interval
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 fluxapyroxad

.

10 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.htmlPage 27 of 34



### Appendix A. Summary of Occupational and Residential Non

- cancer Algorithms

1) RESIDENTIAL

Residential Non

- cancer Handler Algorithms

Dermal and Inhalation Handl er Exposure Algorithm: Daily dermal and inhalation exposure (mg/day) for residential pesticide handlers, for a given

formulation

- application method combination, is estimated by multiplying the formulation

application method

- specific unit exposure by an estimate of the amount of active ingredient handled in a day, using the equation below:

E = UE * AR * A

where:

E = exposure (mg/day); UE = unit exposure (mg/lb ai); AR = application rate (e.g., lb ai/ft 2 

### , lb ai/gal); and

A = area treated or amount handled (e.g., ft 2 

### /day, gal/day).

Residenti al Non

- cancer Dose Calculations

Dermal and/or inhalation absorbed doses normalized to body weight are calculated

as:

D = E *AF / BW
where:

D = dose (mg/kg

- day); E = exposure (mg/day); AF = absorption factor ( dermal and/or inhalation); and BW = body weight (kg).

Residential Non

- cancer Post

- application Algorithms

Post

- application Dermal Exposure Algorithm

– Physical Activities on Turf Exposure resulting from contacting previously treated turf while performing physical activities is calculated as shown below. Residential post

- application exposure assessment must include calculation of exposure on the day of application. Therefore, though an assessment can present exposures for any day “t” following the applica tion, it must include “day 0” exposure.

E = TTRt * CF1 * TC * ETPage 28 of 34



### where:

E = exposure (mg/day); TTRt = turf transferable residue on day t (μg/cm 2 

### ); CF1 = weight unit conversion factor (0.001 mg/μg); TC = transfer coefficient (cm 2 

### /hr); and ET = exposure time (hr/day).

Dermal absorbed doses are calculated as:

where:

D = dose (mg/kg

- day);

E = exposure (mg/day);

AF = absorption factor (dermal); and

BW = body weight (kg).

Table A

- X : Turf (Physical Activities)

-- Inputs for Residential Post

- application Dermal Exposure

Algorithm Notation Exposure Factor (units) Point Estimate(s)

AR Application rate (mass active ingredient per unit area) [input]

F Fraction of AR as TTR

following application (if

chemical

- specific data is unavailable) L/WP/WDG 0.01

Granules 0.002

F D Daily residue dissipation

(if chemical

- specific data is unavailable) (fraction) L/WP/WDG 0.1

Granules 0.1

TC Transfer

Coefficient (cm 2 /hr) L/WP/WDG Adults 180,000
Children 1 < 2 years old 49,000

Granules Adults 200,000

Children 1 < 2 years old 54,000

ET Exposure Time

(hours per day) Adults 1.5 Children 1 < 2 years old 1.5

BW Body Weight (kg) Adults 80

Children 1 < 2 years old 11 L/WP/WDG = Liquids/Wettable Powders/Water

- dispersible Granules



### Post

- application Hand

- to

- Mouth Exposure Algorithm

– Physical Activities on Turf Exposure from hand

- to

- mouth activity is calculated as follows (based on the algorithm utilized in

the SHEDS

- Multimedia model ):

E = [HR * ( F

M 

### * SA H 

### ) * (ET * N_Replen ) * (1

- (1

- SE ) (Freq_HtM/N

- Replen) 

### )]Page 29 of 34



### where:

E = exposure (mg/day); HR = hand residue loading (mg/cm 2 

### ); FM = fraction hand surface area mouthed / event (fraction/event); SAH = typical surface area of one hand (cm 2 

### ); ET = exposure time (hr/day); N_Replen = number of replenishment intervals per hour (intervals/hour); SE = saliva extraction factor (i.e., mouthing removal efficiency); and Freq_HtM = number of hand

- to

- mouth contacts events per hour (events/hour).

and

where:

HR = hand r esidue loading (mg/cm 2 

### );
Fai hands 

### = fraction ai on hands compared to total surface residue from dermal transfer coefficient study (unitless); DE = dermal exposure (mg); and

SA H 

### = typical surface area of one hand (cm 2 

### ).

Dose, normalized to body weight, is calculated as:

where:

D = dose (mg/kg

- day);

E = exposure (mg/day); and

BW = body weight (kg).

Table A

- X : Turf (Physical Activities)

– Inputs for Residential Post

- application Hand

- to

- Mouth Exposure Algorithm
Notation Exposure Factor (units) Point Estimate(s)

Fai hands Fraction of ai on hands

from dermal transfer coefficient study (unitless) Liquid formulations 0.06

Granular formulations 0.027

DE Dermal exposure (mg) Calculated

SA H Typical surface area of one hand (cm 2 ), children 1 < 2 years old 150

AR Application rate

(mass active ingredient per unit area) [input]

HR Residue available on the hands (mg/cm 2 ) Calculated via (DE * Fai hands )/SA HPage 30 of 34

Table A

- X : Turf (Physical Activities)

– Inputs for Residential Post

- application Hand

- to

- Mouth Exposure Algorithm
Notation Exposure Factor (units) Point Estimate(s)

F M Fraction hand surface area mouthed (fraction/event) 0.127

N_Replen Replenishment intervals per hour (intervals/hr) 4

ET Exposure time (hrs/day) 1.5

SE Saliva extraction factor (unitless) 0.48

Freq_HtM Hand

- to

- mouth events per hour (events/hr) 13.9

BW Body Weight

(kg) Children 1 < 2 years old 11



### Post

- application Object

- to

- Mouth Exposure Algorithm

– Physical Activities on Turf Exposure from object

- to

- mouth activity is calculated as follows (based on the algorithm utilized
in SHEDS

- Multimedia):

E = [OR* CF1 * SAM O 

### * (ET * N_Replen) * (1

- (1

- SE O 

### ) (Freq_OtM/N_Replen) 

### )]

where:

E = exposure (mg/day); OR = chemical residue loading on the object on day “t” (ug/cm 2 

### ); CF1 = weight unit conversion factor (0.001 mg/μg);

SAM O 

### = area of the object surface that is mouthed (cm 2 

### /event); ET = exposure time (hr/day); N_Replen = number of replenishment intervals per hour (intervals/hour);

SE O 

### = saliva extraction factor (i.e., mouthing removal efficiency); and Freq_OtM = number of object

- to

- mouth contact events per hour (events/hour).

and

OR = AR * F O 

### * CF 2 * CF3

where:

OR = chemical residue loading on the object (μg/cm 2 

### ); AR = application rate (lbs ai/ft 2 

### or lb ai/acre);

F O 

### = fraction of residue available on the object (unitless); CF2 = weight unit conversion factor (4.54 x 10 8 

### μg/lb); and

CF3 = area unit conversion factor (1.08 x 10 - 3 

### ft 2 

### /cm 2 

### or 2.47 x 10 - 8 

### acre/cm 2 

### ).

Dose, normalized to body weight, is calculated as:Page 31 of 34



### where:

D = dose (mg/kg

- day);

E = exposure (mg/day); and

BW = body weight (kg).

Table A

- X : Turf (Physical Activities)

– Inputs for Residential Post

- application Object

- to

- Mouth Exposure Algorithm
Notation Exposure Factor (units) Point Estimate(s)

AR Application rate (to turf)

(mass active ingredient per unit area) [input]

F O Fraction of AR as OR following application 1 0.01

SAM O Surface area of object mouthed (cm 2 /event) 10

N_Replen Replenishment intervals per hour (intervals/hour) 4

SE O Saliva extraction factor (fraction) 0.48

ET Exposure time (hours per day) 1.5

Freq_OtM Object

- to

- mouth events per hour (events/hr) 8.8

BW Body Weight (kg) Children 1 < 2 years old 11

1 This SOP assumes that all of the residue on the turf could be transferred to the object (e.g., object residue is equal to turf transferable residue).



### Post

- application Incidental Soil Ingestion Exposure Algorithm

– Physical Activities on Turf Exposure from incidental soil ingestion is calculated as follows:

E = SRt * SIgR * CF1

where: E = exposure (mg/day);

SRt = soil residue on day "t" (μg/g); SIgR = ingestion rate of soil (mg/day); and CF1 = weight unit conversion factor (1 x 10 - 6 

### g/μg).

and

E = SRt * SIgR * CF1

SRt = AR * FS * (1

- F D 

### ) t 

### * CF2 * CF3 * CF4

where:Page 32 of 34



### SR t 

### = soil residue on day "t" (μg/g); AR = application rate (lbs ai/ft 2 

### or lb ai/acre); FS = fraction of ai available in uppermost cm of soil (fraction/cm);

F D 

### = fraction of residue that dissipates daily (unitless); T = post

- application day on which exposure is being assessed; CF2 = weight uni t conversion factor (4.54 x 10 8 

### μg/lb); CF3 = area unit conversion factor (1.08 x 10 - 3 

### ft 2 

### /cm 2 

### or 2.47 x 10 - 8 

### acre/cm 2 

### ); and CF4 = soil volume to weight unit conversion factor (0.67 cm 3 

### /g soil).

Dose, normalized to body weight, are calculated as:

where : D = dose (mg/kg

- day);

E = exposure (mg/day); and

BW = body weight (kg).

Table A

- X : Turf (Physical Activities)

– Inputs for Residential Post

- application Incidental Soil Ingestion Exposure Algorithm
Notation Exposure Factor (units) Point Estimate(s)

AR Application rate

(mass active ingredient per unit area) [input]

FS Fraction of AR available in uppermost 1 cm of soil (unitless) 1

F D Daily residue dissipation (fraction) 0.1

SIgR Soil ingestion rate (mg/day) 50

BW Body weight (kg) Children 1 < 2 years old 11



### 2) OCCUPATIONAL EXPOSURE

Occupational Non

- cancer Handler Algorithms

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

where:

E = e xposure (mg ai/day),

UE = u nit e xposure (μ g ai/ lb ai),

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

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

.Page 33 of 34



### The daily doses are calculated using the following formula:

where:

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

E = e xposure (mg ai/day),

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

BW = body weight (kg)

.

Margin of Exposure: Non

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

h andlers a re compared to the appropriate POD ( i.e.

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

where:

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

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

, and

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

.

Occupational Non

- cancer Post

- application Algorithms

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

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

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

t = number of days after application day (days)

.Page 34 of 34



### where:

E = e xposure (mg ai/day),

TC = t ransfer coefficient (cm 2 

### /hr),

DFR t 

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

### ), and

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

The daily doses are calculated using the following formula:

where:

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

E = e xposure (mg ai/day),

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

BW = body weight (kg).

Margin of Exposure: Non

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

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

, NOAEL) to assess the risk to occupational post

- application workers

. All
MOE values a re calculated using the following formula:

where:

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

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

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

Occupational Seed Treatment

See Memorandum: Acres planted per Day and Seeding Rates of Crops Grown in the United States (March 24, 2011)

.

See Memorandum: Reviewer’s Aid to Calculating Occupational Exposures from Activities Related to Agricultural Seed Treatment (November 29, 2012)

.

See Memorandum: Seed Treatment Standard Operating Procedure #14