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

Date:

Subject: May 6, 2013 OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION



### Hexythiazox. Occupational and Re sidentia l Exposure Assessment for a Proposed

Use on Sorghum, Pepper/Eggplant S u bgroup, Caneberry Subgroup, Low Growing Berry Subgroup, Small Vine Climbing Fruit Subgroup and Pome Fruit Group

PC Code: 128849

Decision No.: 466413

Petition No.: 2F8054 DP Barcode: 404018 Registration No.: NA Regulatory Acti on: Risk Assessment Type : OccupationaVResidential Exposure Assessment

TXRNo.:NA Case No.: NA

CAS N o.: 78587-05-0

40 CFR: I 80.448 MRID No. :N A



### From:

Through:

To:

Introduction Alexandra LaM ay, Biologist

Ri sk Assessment Branch VII

Health Effects Division (7509P)

Michael Metzger, Chief

# ~ /)

# ~ (} 

# J.a___

Risk Assessment Branch 

### VII 

# (fo/f

# ~ /

# ~ Health Effects Division (7509P

and

. ,

# ~
Matt hew Lloyd, CIH

# ~ . 

## -J e

# ~s Je ffEvans, Environmen ta l Scientist

# r~~ {:.r 

# {€-

Exposure Science Adv iso ry Committee (ExpoSAC) 

### I HED

Olga Odiott Registration Division (7505P)

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

exposure and risk assessment for the proposed ne w use ofhexythiazox on sorghum and the IR-4 proposed uses on the pepper/eggplant subgroup 8-1 OB, pome fruit group 11-10, caneberry subgroup 13-07 A, small fruit climbing subgroup 13 -07F, and low growing b erry s u bgroup 13

- 

## 070.

Page I of21

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

data were used in this assessment as surrogate data in the absence of chemical-specific data, including Pesticid e Handlers Exposure Database Version 1.1 (PHED 1.1) ; the Agric ultural

Handler Exposure Task Force (AHET F ) databa se; the Outdoor R esidential Exposure T ask Force (ORETF) database ; the Agricultura l Reentry Task Fo rce (ARTF) databa se; and the Residential

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

Federa l Insecticid e, Fung i c ide

, and Rodenti c i de Act (F IFRA )

.

Note: 

### This memorandum was reviewed by the Exposure Science Advisory Committee (ExpoSAC) on March 28, 2013.

P age 2 of2 1Page 3 of 21 

### Table of Contents

1.0 Executive Summary

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

2.0 Risk Assessment Conclusions and Recommendations

................................ ........................ 5

2.1 Data Deficiencies and Requirements

................................ ................................ ............... 5

3.0 Hazard Characterization

................................ ................................ ................................ ....... 6

4.0 Us e Profile

................................ ................................ ................................ ........................... 7

5.0 Residential Exposure and Risk Estimates

................................ ................................ ............ 9

5.1 Residential Handler Exposure/Risk Estimates

................................ ................................ . 9

5.2 Residential Post

- application Exposure/Risk Estimates

................................ .................. 10

5.3 Combined Residential Risk Estimates (Multiple Exposure Scenarios)

......................... 11

5.4 Residential Risk Estimates for Use in Aggregate Assessment

................................ ...... 11

5.5 Spray Drift

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

5.6 Residential Bystander Post

- Application Inhalation Exposure

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

6.0 Occupational Exposure and Risk Estimates

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

6.1 Occupational Handler Exposure/Risk Estimates

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

6.2 Occupational Post

- application Exposure/Risk Estimates

................................ .............. 19

6.2.1 Occupational Post

- application Inhalation Exposure/Risk Estimates

...................... 19

6.2.2 Occupational Post

- application Dermal Exposure/Risk Estimates

.......................... 19 Appendix A. Summary of Occupational Non

- cancer Algorithms

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



### 1.0 Executive Summary

This occupational and residential exposure and risk assessment was completed for the new uses of hexythiazox on sorghum proposed by Gowan and the IR

- 4 proposed uses on the pepper/ eggplant subgroup 8

- 10B, pome fruit group 11

- 10, caneberry subgroup 13

- 07A, small fruit climbing subgroup 13

- 07F , and low growing berry subgroup 13

- 07G. The proposed application rate is up to 0. 1875 lb ai/acre or 0.0625 lb ai/100 gal.

There are currently registered uses of hexythiazox use on pome fruit, caneberry, grape and strawberry; however, this assessment was completed also including these crops bec ause many exposure factors have been updated since the last a ssessment of these crops and all crops in the petitions are included in this assessment as appropriate.

Hexythiazox has low acute toxicity by the oral, dermal and inhalation routes of exposure. It produces mild eye irritation, is not a dermal irritant, and is negative for dermal sensitization.

Short

- and intermediate

- term incidental oral and inhalation risks are regulated based on

decreased pup body weight during lactation and delays in hair growth and/or eye opening, decreased parental body

- weight gain and increased liver, kidney, and adrenal weights in the 2

- generation reproduction study in the rat. For the short

- and intermediate

- term der mal risk assessment, no quantification of risk is required, based on the fact that the oral equivalent dose for this dermal exposure scenario is 1.5

- fold greater than the limit dose.

There are no proposed residential uses at this time; however, there are existing residential uses that were previously assessed (A. LaMay, D396864, 9/25/12). Residential handler inhalation margins of exposure (MOEs) significantly exceed 100 for all scenarios assessed and are not of concern. Child incidental oral exposure to treated turf was assessed for hexythiazox; risk estimates are not of concern (MOEs > LOC) for all scenarios.

Occupational handler inhalation MOEs significantly exceed 100 for all scenarios assessed associated with the proposed uses and are not of concern. No quantification of dermal risk is required as no dermal hazard was identified.

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

- cancer occupational post

- application inhalation exposure assessment was not performed for hexythiazox at this time. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational
post

- application inh alation exposure assessment for hexythiazox

.

Since hexythiazox is classified in Acute Toxicity Category III for pr imary eye irritation and Acute Toxicity Category IV for acute dermal toxicity and irritation, the Worker Protection Standard (WPS) restricted

- entry interval (REI) for hexythiazox is 12 hours.

Human Studies Review

This risk assessment relies in part on da ta from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical. These data, which include studies from PHED 1.1; the AHETF database; the Outdoor Residential Exposure Task Force (ORETF)Page 5 of 21



### database; the ARTF database ; and the Residential SOPs, 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

Stud ies 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/residential risk estimates of concern associated with the proposed new uses of hexythiazox. There are no data gaps in the exposure database. A s quantification of dermal risk is not required for hexythiazox, a dislodgeable foliar residue (DFR) study is not required for hexythiazox at this time. Additionally, a TTR study is not required for hexythiazox

at this time since the hand

- to

- mouth MOE for children is >1,000 based on default values for the fraction of application rate availa ble for transfer after a turf application.

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 cour ses, 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 ne w liquid and granular default values for the

fraction of the application rate available 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 pr oduct 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 c alculated 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 margin of safety for any potentially higher

residues seen in a chemical

- spe cific 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 study is not required for hexythiazox at this time

since the hand

- to

- mo uth 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 (DFR): In accordance with the updated Part 158 data requirements (2007), one o r more DF R stud ies are required when a pesticide has residential or occupational

uses t hat could result in post

- application dermal exposure. A DF R st udy is not required for hexythiazox at this time since quantification of dermal risk is not required for h exythiazox

.

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

- exposure

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

- app

- exposure

- data.html

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

- exposure

- sop.htmlPage 6 of 21



### 3 .0 Hazard Characterization

Acute Toxicity Hexythiazox has a low order of acute toxicity and is classified as Toxicity Category IV for the oral, dermal and inhalation routes of exposure. It produces mild eye irritation (reddened conjunctiva) (Toxicity Category III), is not a dermal irritant (Toxic ity Category IV), and is negative for dermal sensitization.

Table 3 .0 .1. Acute Toxicity Data on Hexythiazox Technical.

Guideline No./ Study Type MRID No. Results Toxicity Category

870.1100 Acute oral toxicity 00146549 LD 50 = >5000 mg/kg IV

870.1200 Acute dermal toxicity 00146550 LD 50 = >5000 mg/kg IV

870.1300 Acute inhalation toxicity 00146554 LC 50 = >2.0 mg/L IV

870.2400 Primary eye irritation 00146551 Reddened conjunctiva III

870.2500 Acute dermal irritation 00146552 Non irritant IV

870.2600 Skin sensitization 00146553 Non sensitizer N/A



### Toxicological PODs Used for Risk Assessment The toxicity endpoints and PoDs for the hexythiazox risk assessment are shown in Table 3.0 .2.

Short

- and intermediate

- term incidental oral and inhalation risks are regulated based on

decreased pup body weight during lactation and delays in hair growth and/or eye opening, decreased parental body

- weight gain and increased liver, kidney, and adrenal weights in the 2

- generation reproduction study in the rat. 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.

For the short

- and intermediate

- term dermal risk assessment, no quantification of risk is required,

based on the fact that the oral equivalent dose for this dermal exposure scenario is 1.5

- fold greater than the limit dose.

Hexythiazox is classified as “likely to be carcinogenic to humans”; however the evidence as a whole is not strong enough to warrant a quantitative estimati on of human risk. Since the effects seen in the study that serves as the basis for the chronic reference dose (RfD) occurred at doses substantially below the lowest dose that induced tumors, the chronic RfD is considered protective of all chronic effects including potential carcinogenicity of hexythiazox.

Table 3. 0 .2. Summary of Toxicological Dose and Endpoints for Occupational and Residential Hexythiazox Exposure

Assessments.Page 7 of 21

Exposure

Scenario POD UFs and LOC for Risk

Assessment Study and Toxicological Effects

Dermal Short

- and

Intermediate Term (1

- 30 days and 1

– 6 months) N/A N/A No dermal hazard identified

Inhalation Short

and

Intermediate

Term (1

– 30 days

and 1

- 6 months) Oral NOAEL = 30

mg/kg/day

Inhalation hazard assumed to

be equivalent to oral hazard UF A =10x

UF H =10x

Residential LOC for

MOE = 100

Occupational LOC for

MOE = 100 2

- Generation Reproduction Study

– Rat

LOAEL = 180 mg/kg/day, based on decreased pup body weight during lactation and delayed hair growth and/or eye op ening, and decreased parental body

- weight gain and increased absolute and relative liver, kidney, and adrenal weights

Co

- critical

13

- Week Feeding Study

– Rat LOAEL = 38.1 mg/kg/day, based on increased absolute and relative liver weights in both sexes,

inc reased relative ovarian and kidney weights, and fatty degeneration of the adrenal zona fasciculate.

Short

- and

Intermediate

Term Incidental oral (1

- 30 days

and 1

- 6 months) NOAEL=30 mg/kg/day UF A = 10x

UF H = 10x FQPA SF= 1x

Residential LOC for

MOE = 100 2

- Generation Reproduction Study

– Rat

LOAEL = 180 mg/kg/day, based on decreased pup body weight during lactation and delayed hair growth and/or eye opening, and decreased parental body

- weight gain and increased absolute and relative liver, kidney, and adr enal weights

Cancer (oral, dermal, inhalation) Classification: “Likely to be Carcinogenic to Humans”. Insufficient evidence to warrant a quantitative

estimation of human risk based on the common liver tumors (benign and malignant) observed only in high d ose female mice, and benign mammary gland tumors of no biological significance, observed only in high dose male rats in the absence of mutagenic concerns. The chronic RfD is protective of all chronic effects including potential carcinogenicity of hexythia zox. 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

obs erved 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 human population (interspecies). FQPA SF = FQPA Safety Factor. MOE = margin of exposure. LOC = level of concern. N/A = not applicable.



### Absorption Since no inhalation absorption data are available, toxicity by the inhalation route is considered to be equivalent to the estimated toxicit y 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

The required PPE on the Savey® 50 DF Ovicide/Miticide label and the Onager Miticide label is applicators and other handlers must wear long

- sleeved shirt and long pants, waterproof gloves, shoes plus socks.Page 8 of 21

Table 4 .1. Su mmary of Directions for Use of Hexythiazox

. Applic. Timing, Type, and Equip. Formulation

[EPA Reg. No.] Applic. Rate (lb ai/A) Max.

No. Applic. Max. Applic.

Rate (lb

ai/A /yr ) PHI

(days) Use Directions and

Limitations

Sorghum

Sorghum (Western US including

Oklahoma and

Texas only) Onager® Miticide

Emulsifiable

concentrate
EPA Reg. No.

10163

- 277

11.8% ai (1 lb ai/gallon) 10

– 24 oz/acre

(0.1 875 lb ai/acre) 1 24 oz/ A /year 30 May apply by ground

application, air application, or chemigation

Caneberry Subgroup 13

- 07A

Ground, Air Savey® 50 DF

Ovicide/Miticide
Water Dispersible Granule (WDG)
EPA Reg. No.

10163

- 250

50% ai 4

- 6 oz/acre ( up to

0.1875 lb ai/acre) 1 6 oz/ A/year 3 For air application, apply a minimum of 5 gallons finished spray per acre.
Applications may be made
post harvest.

Pome Fruit Group 11

- 10

Ground, Air Savey® 50 DF

Ovicide/Miticide
Water Dispersible Granule (WDG)
EPA Reg. No.

10163

- 250

50% ai 3

- 6 oz/acre

(up to 0.1875 lb ai/acre) 1 6 oz/A/year 28 For air applications, apply a minimum of 5 gallons

finished spray per acre.

Ground, Air, Chemigation Onager® 1E

Miticide

Emulsifiable

concentrate
EPA Reg No.

10163

- 277

11.8% ai
1 lb ai/gal 12

- 24 oz/acre

(up to 0.1875 lb ai/A) 1 24 oz/A/year 28 For application by ground equipment, use sufficient

volume of water to obtain complete coverage but not

less than 20 GPA.
For application by air, use

sufficient volume of water to obtain complete coverage but not less than

10 GPA.

Low Growing Berry Subgroup 13

- 07G

Ground, Air Savey® 50 DF

Ovicide/Miticide
Water Dispersible Granule (WDG)

EPA Reg. No.

10163

- 250

50% ai 6 oz/acre

(0.1875 lb ai/A) 1 6 oz/A/year 3 For air applications, apply a minimum of 5 gallons finished spray per acre.
Do not use in strawberry

nurseries.

Small Fruit Vine Climbing Subgroup, Except Fuzzy Kiwifruit 13

- 07F

Ground Onager® Miticide

Emulsifiable 12

- 24 oz/acre

(up to 0.1875 lb 1 24 oz/A/year 7 Application by ground equipment only. UsePage 9 of 21

Table 4 .1. Su mmary of Directions for Use of Hexythiazox

. Applic. Timing, Type, and Equip. Formulation

[EPA Reg. No.] Applic. Rate (lb ai/A) Max.

No. Applic. Max. Applic.

Rate (lb

ai/A /yr ) PHI

(days) Use Directions and

Limitations

concentrate
EPA Reg. No.

10163

- 277

11.8% ai (1 lb ai/gallon) ai/A) sufficient volume of water

to obtain complete coverage but not less than

20 GPA.

Pepper/Eggplant Subgroup 8

- 10B

Ground, Air, Chemigation Onager® 1E

Miticide

Emulsifiable

concentrate
EPA Reg No.

10163

- 277

11.8% ai

( 1 lb ai/gal) 12

- 24 oz/acre

(up to 0.1875 lb ai/A) 1 24 oz/A/year 1

-

Ground, Air,

Handheld Hexygon® DF

dry flowable

50% ai
EPA Reg. No.

10163

- 251 1

- 2 oz/100 gal

(dilute) (up to

0.0625 lb ai/100 gal)

3

- 6 oz/A (conc.) (up to 0.1875 lb ai/A)

0.0 7

- 0.14 oz/1000 sq. ft. (up

to 0.0044 lb ai/ 1000 sq. ft. ) 1 24 oz/A/year 1 Pepper/Eggplant Sub g roup 8

- 10B (including greenhouse)



### 5 .0 Residential Exposure and Risk Estimates

There are no proposed residential uses at this time; however, there are existing residential uses

that have been previously assessed (A. LaMay, D396864, 9/ 25/12)

. The assessment was completed for a dry flowable product containing 50% hexythiazox active ingredient registered for use on several residential sites, including (1) ornamental landscape plantings in residences, public areas, and recreational sites such as campgrounds, golf courses, parks and athletic fields, (2) ornamental lawns and turf (including residential), (3) residential pome fruit, stone fruit, and nut trees, and residential caneberries. The previous assessment reflect s updates to HED’s 2012

Residential SOPs 3 

### along with policy changes for body weight assumptions

. Th e risk estimates from the previous assessment are shown in this memorandum to be used for the aggregate

assessment.

5 .1 Residential Handler Exposure/Risk Es timates

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

- exposure

- sop.htmlPage 10 of 21



### HED uses the term “handlers” to describe those individuals who are involved in the pesticide application process.

Summary of Residential Handler Non

- Cancer Exposure and Risk Estimates

Residential handler inhalation risk estimates are not of concern (MOEs > LoC). Inhalation MOEs range from 420,000 (mixing/loading/applying dry flowable formulation to gardens/trees by manually

- pressurized handwand or backpack) to 330 million (mixing/loadi ng/applying dry flowable formulation to gardens/trees by hose

- end sprayer). Dermal MOEs were not quantified because no hazard was identified via the dermal route for hexythiazox. A summary of inhalation

risk estimates for residential handlers can be foun d in Table 5.1.1.

Table 5.1.1. Short

- term Residential Handler Non

- cancer Exposure and Risk Estimates for Hexythiazox.

Exposure Scenario Target MOE Inhalation

Unit Exposure (mg/lb ai) Maximum

Application

Rate 1 Area Treated or

Amount Handled Daily 2 Inhalation

Dose (mg/kg/day) 3 MOE 4

Mixer/Loader/Applicator

Lawns/ Turf; Gardens/Trees, WDG/DF, Manually

- pressurized handwand / backpack 100 1.1 0.000625 lb ai/gallon 5 gallons 0.000043 700,000

Gardens/ Trees, WDG/DF, Hose

- end

sprayer 100 0.0014 4.375E

- 6 lb

ai/ft 2 1200 ft 2 0.000000092 330,000,000

Gardens/ Trees, WDG/DF, Hose

- end

sprayer 100 0.0014 0.000625 lb ai/gallon 11 gallons 0.00000012 250,000,000

Lawns/ Turf, WDG/DF, Hose

- end

sprayer 100 0.022 0.1875 lb ai/acre 0.5 acres 0.000026 1,200,000

Gardens/Trees, WDG/DF, Manually

pressurized handwand / backpack 100 1.1 4.375E

- 6 lb

ai/ft 2 1200 ft 2 0.000072 420,000

1 Based on registered label (Reg. No. #10163

- 251).

2 Exposure Science Advisory Council Policy #9.1.

3 Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) x Application Rate (lb ai/acre or gal) x Area Treated or Amount Handle d (A or gallons/day) / BW (80 kg).

4 Inhalation MOE = Inhalation NOAEL (30 mg/kg/day) / Inhalation Dose (mg/kg/day).



### 5

. 2 Residenti al 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 hexythiazox

. As no dermal hazard was identified, only in cidental oral exposure for children was quantitatively assessed.

Summary of Residential Post

- application Non

- Cancer Exposure and Risk Estimates Child incidental oral exposure to treated turf was assessed for hexythiazox. Risk estimates range from 11,000 for hand

- to

- mouth short

- term exposure to 4,700,000 for incidental soil ingestion

short

- and intermediate

- term exposure. Risk estimates are not of concern (MOEs > LOC) for all

scenarios.

Table 5.2.1. Residential Post

- application Non

- cancer Exposure and Risk Estimates for Hexythiazox (Short

- Term for Hand

- to

- Mouth and Object

- to

- Mouth Exposure; Short

- and
Intermediate

- Term for Incidental Soil Ingestion Exposure).Page 11 of 21 Lifestage Post

- application Exposure Scenario App rate 1 Dose MOEs 2

Child Turf

- sprays Hand to Mouth

0.1875 lb ai/acre 0.0029 11,000
Object to Mouth 0.00009 350,000 Incidental Soil Ingestion 0.0000063 4,700,000

1 Based on registered uses

. 2 MOE = POD (mg/kg/day) ÷ Dose (mg/kg/day).



### 5 .3 Combined Residential Risk Estimates (Multiple Exposure Scenarios)

There are no multiple exposure scenarios relevant for the registered or proposed uses.

5

. 4 Residential Risk Estimates for Use in Aggregate Assessment

Table 5.4.1 reflects the residential risk estimates that are recommended for use i n the aggregate assessment for hexythiazox. The recommended residential exposure for use in the adult aggregate assessment reflects inhalation exposure from application to gardens/trees via manually

- pressurized handwand / backpack sprayer;

The recommended residential exposure for use in the children 1<2 years old aggregate assessment reflects incidental oral exposures from post

- application exposure to treated

turf.Page 12 of 21

Table 5

. 4 .1. Recommendations for the Residential Exposures for the Hexythiazox Aggregate Assessment

.

Lifestage Residential Handler Residential Post

- application

Dose (mg/kg/day) 1 MOE 2 Dose (mg/kg/day) 3 MOE 4

Dermal Inhalation Total Dermal Inhalation Total Dermal Inhalation Oral Total Dermal Inhalation Oral Total

Short

- Term

Adult Male N/A 0.000072 0.000072 N/A 420,000 420,000 N/A N/A N/A N/A N/A N/A N/A N/A

Adult Female N/A 0.000072 0.000072 N/A 420,000 420,000 N/A N/A N/A N/A N/A N/A N/A N/A

Child N/A N/A N/A 0.0029 0.0029 N/A N/A 11,000 11,000

Intermediate

- Term

Adult Male

N/A N/A N/A N/A N/A N/A N/A N/A N/A

Adult Female N/A N/A N/A N/A N/A N/A N/A N/A

Child N/A N/A 0.0000063 0.00000

63 N/A N/A 4,700,000 4,700,000

1 Residential Handler Dose = the highest handler dose for each applicable lifestage of all scenarios assessed from Table 5.1.1

. Total = dermal + inhalation.

2 Residential Handler MOE = the MOEs associated with the highest doses identified in Table 5.1.1.

3 Residential Post

- application Dose = the highest post

- application dose for each applicable lifestage of all scenarios assessed from Table 5.2.1. Total = dermal + inhalation + incidental oral, where applicable.

4 Residential Post

- application MOE = the MOE s associated with the highest doses identified in Table 5.2.1.Page 13 of 21



### 5

. 5 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 hexythiazox

. 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 D rift website for more information 4



### . The Agency has completed its evaluation of the new database submitted by the Spray Drift Task Force, a membership of U.S. pesticide registrants, and is developing a policy on how to appropriately apply the data and the AgDRIFT computer model to its risk assessments for pesticides applied by air, orchard airblast and ground hydraulic methods. After the policy is in place, the Agency may impose further refinements in spray drift management practices to reduce

off

- target d rift 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 f ields, 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 inhalat ion exposure scenarios

.

It is noted that the 0.19 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 scen ario is protective of any exposure of farm children via spray drift from agricultural hexythiazox applications.

5

. 6 Residential Bystander Post

- Application Inhalation Exposure

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

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

inhalation tox icity (Toxicity Category IV) and low vapor pressure ( 2.3 x 10 - 8 

### mmHg ) . However, volatilization of pesticides may be a source of post

- application inhalation exposure to individuals nearby pesticide applications. The Agency sought expert advice and input on issues related to volatilization of pesticides from it s Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 5



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

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

application inhalation exposure assessment for hexythiazox

.

Although a quantitative residential post

- application inhalation exposure assessment was not performed, an inhalation exposure assessment was performed for handlers (i.e., groomers,

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

5 Available: http://www.epa.gov/scipoly/SAP/meetings/200 9/120109meeting.htmlPage 14 of 21



### treaters, etc). This exposure scenario is representative of a worse case inhalation exposure and should be considered protective of most post

- application inhalation exposure scenarios.

6 .0 Occupational Exposure and Risk Estimates

6 .1 Occupational Handler Exposur e/Risk Estimates

HED uses the term handlers to describe those individuals who are involved in the pesticide application process. HED believes that there are distinct job functions or tasks related to applications and exposures can vary depending on the specifics of each t ask. Job requirements (amount of chemical used in each application), the kinds of equipment used, the target being treated, and the level of protection used by a handler can cause exposure levels to differ in a manner specific to each application event.

Based on the anticipated use patterns and current labeling, types of equipment and techniques that can potentially be used, occupational handler exposure is expected from the proposed uses. The quantitative exposure/risk assessment developed for occupatio nal handlers is based on the following scenarios:

Mixing/Loading dry flowable for ground, air, and chemigation application; Mixing/Loading emulsifiable concentrate for ground, air, and chemigation application; Applying spray by aerial and ground equipmen t; Flagging in support of aerial application; and Mixing/Loading/Applying dry flowable for handheld equipment application.

Occupational Handler Exposure Data and Assumptions

A series of assumptions and exposure factors served as the basis for completing the occupational handler risk assessments. Each assumption and factor is detailed below on an individual basis.

Application Rate : Application rates for all proposed uses are listed in Section 4.0. Application rates assessed were

0.1875 lb ai/acre or 0.0625 lb ai/100 gallons.

Unit Exposures: It is the policy of HED to use the best available data to assess handler exposure. Sources of generic handler data, used as surrogate data in the absence of chemical

- specific data, include PHED 1.1, the AHETF database, 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 standa rd 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 6 

### ”, which, along with additional informatio n on HED policy on use of surrogate data, including descriptions of the various sources, can be found at the Agency website 7



### .

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

- exposure

- table.pdf

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

- exposure

- data.htmlPage 15 of 21



### Area Treated or Amount Handled : Area treated or amount handled includes:
Aerial equipment : 350 acres orchard or field crops; 1 200 acres for high

- acreage field crops Groundboom equipment: 60 acres for greenhouse; 80 acres for field crops; 200 acres for high

- acreage field crops Airblast equipment: 40 acres for orchards Handheld equipment: 40

– 1000 gallons



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

- term and exposures 30 days to six months

as intermediate

- term. Exposure duration is determined by many things, including the exposed population, the use site, the pest pressure triggering the use of the pesticide, and the cultural practices surrounding that use site. For most agricultural uses, it is reasonable to believe that occupational handlers will not apply the same chemical every day for more than a one

- month time frame; however, there may be a la rge agribusiness and/or commercial applicators who may apply a product over a period of weeks (e.g., completing multiple applications for multiple clients within a region).

For hexythiazox, based on the proposed uses, short

- term exposures are anticipated as the proposed uses indicate the product is only to be applied once per year. As the inhalation point of departure is the same for both short

- and intermediate

- term exposure durations, the short

- term assessment is protective of possible longer

- term exposures (i.e., commercial applicators that may apply a product over a period of weeks).

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 consisting of a long sleeved shirt, long pants, shoes plus socks, no protective gloves, and no respirator, as well as baseline with various levels

of PPE as nece ssary (e.g., gloves, respirator, etc). The hexythiazox product labels direct handlers

to wear long

- sleeved shirt and long pants, waterproof gloves, shoes plus socks

.

Occupational Handler Non

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

- cancer exposure and dose for occupational handlers can be found in Appendix A

.

Combining Exposures/ Risk Estimates :

Dermal and inhalation risk estimates were not combined in this assessment, since no dermal hazard was identified; therefor e no dermal quantitative risk assessment is required.

Summary of Occupational Handler Non

- Cancer Exposure and Risk Estimates Occupational handler inhalation risk estimates are not of concern (MOEs > LOC) for all proposed uses assessed. Inhalation MOEs range from 4,100 (mixing/loading dry flowable formulation in support of aerial and chemigation application to orchards/field crops) to 7.4 million ( aerial application to orchards/field crops ). A summary of inhalation risk estimates for occupational handle rs can be found in Table 6.1.1.Page 16 of 21



### The Agency matches quantitative occupational exposure assessment with appropriate characterization of exposure potential. While HED presents quantitative risk estimates for human flaggers where appropriate, agricultural avi ation has changed dramatically over the past two decades. According the 2012 National Agricultural Aviation Association (NAAA) survey of their membership, the use of GPS for swath guidance in agricultural aviation has grown steadily
from the mid 1990’s. Ov er the same time period, the use of human flaggers for aerial pesticide applications has decreased steadily from ~15% in the late 1990’s to only 1% in the most recent (2012) NAAA survey. The Agency will continue to monitor all available information sources to best assess and characterize the exposure potential for human flaggers in agricultural aerial applications.

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

- sleeve shirt, long pants, shoes, and socks); per the Agency’s Worker Protection Standard stipulations for engineering controls, pilots are not required to wear protective gloves for the duration of the application . With this level of protection, there ar e no risk estimates of concern for applicators.Page 17 of 21

Table 6.1.1. Short

- /Intermediate

- Term Occupational Exposure and Risk Estimates for Hexythiazox

. All estimates are at baseline mitigation (without respirator).

Exposure Scenario Crop or Target Inhalation Unit Exposure (ug/lb ai) 1 Maximum

Application Rate 2 Area Treated

or Amount Handled Daily 3 Inhalation

Mitigation Level Dose (mg/kg/day) 4 MOE 5

Mixer/Loader

M/L, DF/WDG, Aerial, Broadcast Orchard, Field Crop

8.96 0.1875 lb ai/acre 350 acres 0.00735 4

, 100

M/L, DF/WDG, Airblast,

Broadcast Orchard 40 acres 0.00084 36,000

M/L, DF/WDG, Chemigation,

Broadcast Orchard, Field Crop 350 acres 0.00735 4

, 100

Greenhouse 60 acres 0.00126 24,000

M/L, DF/WDG, Groundboom,

Broadcast Greenhouse 60 acres 0.00126 24,000

Field Crop 80 acres 0.00168 18,000

M/L, L/SC/EC, Aerial, Broadcast Orchard, Field Crop

0.219 0.1875 lb ai/acre 350 acres 0.00018 170,000

High

- acreage Field Crop 1200 acres 0.000616 49,000

M/L, L/SC/EC, Airblast, Broadcast Orchard 40 acres 0.0000205 1,500,000

M/L, L/SC/EC , Chemigation,

Broadcast Orchard, Field Crops (all) 350 acres 0.00018 170,000

M/L, L/SC/EC, Groundboom,

Broadcast Field Crop 80 acres 0.0000411 730,000

High

- acreage Field Crop 200 acres 0.000103 290,000

Applicator

Applicator, Spray, Aerial,

Broadcast Orchard, Field Crop Engineering Control:

0.0 049

0.1875 lb ai/acre 350 acres 0.000004 7,400,000

High

- acreage Field Crop 1200 acres 0.000014 2,200,000

Applicator, Spray, Airblast,

Broadcast Orchard 4.71 40 acres 0.000441 68,000

Applicator, Spray, Groundboom,

Broadcast Greenhouse

0.34 60 acres 0.0000479 630,000

Field Crop 80 acres 0.0000638 470,000

High

- acreage Field Crop 200 acres 0.00016 190,000

Flagger

Flagger, Spray, Aerial, Broadcast Orchard, Field Crop (all) 0.35 0.1875 lb ai/acre 350 acres 0.000288 100,000

Mixer/Loader/ApplicatorPage 18 of 21

Table 6.1.1. Short

- /Intermediate

- Term Occupational Exposure and Risk Estimates for Hexythiazox

. All estimates are at baseline mitigation (without respirator).

Exposure Scenario Crop or Target Inhalation Unit Exposure (ug/lb ai) 1 Maximum

Application Rate 2 Area Treated

or Amount Handled Daily 3 Inhalation

Mitigation Level Dose (mg/kg/day) 4 MOE 5

M/L/A, DF/WDG, Backpack,

Broadcast Greenhouse 140 0.000625 lb ai/gallon 40 gallons 0.0000438 680,000

M/L/A, DF/WDG, Manually

pressurized Handwand, Broadcast Greenhouse 30 0.000625 lb ai/gallon 40 gallons 0.00000938 3,200,000

M/L/A, DF/ WDG, Mechanically

pressurized Handgun , Broadcast Greenhouse 120 0.000625 lb ai/gallon 1000 gallons 0.000938 32,000

1 Based on “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table”

. 2 Based on register ed or proposed label

. 3 Exposure Science Advisory Council Policy #9.1.

4 Inhalation Dose = Dermal Unit Exposure (ug/lb ai ) x Conversion Factor (0.001 mg/ug) x Application Rate (lb ai /acre or gal) x Area Treated or Amount Handled Daily (A or gal/day) /BW (80 kg).

5 Inhalation MOE = Inhalation NOAEL (30 mg/kg/day)/ Inhalation Dose (mg/kg/day).Page 19 of 21



### 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

- application exposure levels vary over time and depend o n such things as the type of acti vity, 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 hexythiazox at this time primarily because of the low acute inhalation toxicity (Toxicity Category IV) and low vapor pressure ( 2.3 x 10 - 8 

### mmHg ) . However, there are multiple potential sources of post

- application inhalation exposure to individuals performing post

- appl ication 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 volatiliza tion 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 8



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

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

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

- application inhalation exposure asses sment for hexythiazox

.

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 applicati on 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 scena rios.

The Worker Protection Standard for Agricultural Pesticides contains requirements for protecting workers from inhalation exposures during and after greenhouse applications through the use of ventilation requirements [40 CFR 170.110, (3) (Restrictions associated with pesticide applications)].

6

. 2 .2 Occupational Post

- application Dermal Exposure/Risk Estimates

As no dermal hazard has been identified for hexythiazox, quantification of dermal post

application risk is not required. In accordance with the updated Part 158 data requirements

8 Available: http://www.epa.gov/scip oly/SAP/meetings/2009/120109meeting.htmlPage 20 of 21



### (2007), one or more dislodgeable foliar residue (DFR) studies are required when a pesticide has residential or occupational uses that could result in postapplication dermal exposure. However, as quantification of dermal risk is not required for hexythiazox, a DFR study is not required for hexythiazox at this time.

Restricted Entry Interval

The REI specified on the proposed label is based on the acute toxicity of hexythiazox. Hexythiazox is classified as Toxicity Category IV for acute dermal toxicity, Toxicity Category IV for acute dermal irritation, and Toxicity Category III for eye irritation. It is not a skin

sensitizer. Under WPS for agricultural pesticides, ai’s classified as Acute III or IV for acute dermal, eye irritation and primary skin irritation are assigned a 12

- hour REI. Therefore, the WPS interim REI of 12 hours is adequate to protect agricultural workers from post

- application exposures to hexythiazox.Page 21 of 21



### Appendix A. Summ ary of Occupational Non

- cancer Algorithms

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)

.

The daily doses are calculated using the following formula:

whe re:

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 t o 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)

.