UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

Date: 

Subject: 

May 6, 2013 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

Hexythiazox. Occupational and Residential Exposure Assessment for a Proposed 

Use on Sorghum, Pepper/Eggplant Subgroup, 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 Action: 

Risk Assessment Type: OccupationaVResidential Exposure Assessment 

TXRNo.:NA 

Case No.: NA 

CAS No.: 78587-05-0 

MRID No.:NA 40 CFR: I 80.448 

From: 

Through: 

To: 

Introduction 

Alexandra LaMay, Biologist 

Risk Assessment Branch VII 

Health Effects Division (7509P) 

Michael Metzger, Chief ~ /) ~ (} J.a___ 

Risk Assessment Branch VII (fo/f ~ / ~ Health Effects Division (7509P 

and ., ~ 

Matthew Lloyd, CIH ~ . -Je ~s JeffEvans, Environmental Scientist r~~ {:.r {€-

Exposure Science Advisory Committee (ExpoSAC) I HED 

Olga Odiott 

Registration Division (7505P) 

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

exposure and risk assessment for the proposed new 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 berry subgroup 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 Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1); the Agricultural 

Handler Exposure Task Force (AHETF) database; the Outdoor Residential Exposure Task Force 

(ORETF) database; the Agricultural Reentry Task Force (ARTF) database; and the Residential 

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

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). 

Note: This memorandum was reviewed by the Exposure Science Advisory Committee 

(ExpoSAC) on March 28, 2013. 

Page 2 of21 
Page 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 Use 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............................................... 21
Page 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 because many 

exposure factors have been updated since the last assessment 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 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.

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 inhalation exposure assessment for hexythiazox.

Since hexythiazox is classified in Acute Toxicity Category III for primary 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 data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical. These data, which include studies from 

PHED 1.1; the AHETF database; the 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 

Studies Review Board. Descriptions of data sources, as well as guidance on their use, can be 

found at the Agency website1. 

2.0 Risk Assessment Conclusions and Recommendations

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. As 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 available 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 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 available for transfer after a turf application (FAR).

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 FAR value seen using a liquid product was 6.1%

or 6.1 times higher than the default residue transfer value. The maximum FAR 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 margin 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 study is not required for hexythiazox 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 (DFR): In accordance with the updated Part 158 data requirements 

(2007), one or more DFR studies are required when a pesticide has residential or occupational 

uses that could result in post-application dermal exposure. A DFR study is not required for 

hexythiazox at this time since quantification of dermal risk is not required for hexythiazox.

 

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.html
Page 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 (Toxicity 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 LD50 = >5000 mg/kg IV

870.1200 Acute dermal toxicity 00146550 LD50 = >5000 mg/kg IV

870.1300 Acute inhalation toxicity 00146554 LC50 = >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 estimation 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 Shortand

IntermediateTerm (1 – 30 days 

and 1-6 months)

Oral NOAEL = 30 

mg/kg/day

Inhalation hazard assumed to 

be equivalent to oral hazard

UFA=10x

UFH=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 opening, 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, 

increased relative ovarian and kidney weights, and 

fatty degeneration of the adrenal zona fasciculate.

Short- and 

IntermediateTerm Incidental 

oral (1-30 days 

and 1-6 months)

NOAEL=30 mg/kg/day

UFA = 10x

UFH = 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 adrenal 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 dose 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 hexythiazox.

Point of Departure (PoD) = A data point or an estimated point that is derived from observed dose-response data and used to mark 

the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no 

observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UFA = extrapolation 

from animal to human (intraspecies). UFH = potential variation in sensitivity among members of the human population 

(interspecies). 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 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 

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. Summary 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

(0.1875 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. Use 
Page 9 of 21

Table 4.1. Summary 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)

0.07- 0.14 

oz/1000 sq. ft. (up 

to 0.0044 lb ai/ 

1000 sq. ft.)

1 24 oz/A/year 1

Pepper/Eggplant Subgroup 

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 reflects updates to HED’s 2012 

Residential SOPs3along with policy changes for body weight assumptions. The risk estimates

from the previous assessment are shown in this memorandum to be used for the aggregate 

assessment.

5.1 Residential Handler Exposure/Risk Estimates

 

3 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
Page 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/loading/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 found 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 

Rate1

Area Treated or 

Amount 

Handled Daily2

Inhalation

Dose 

(mg/kg/day)3 MOE4

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/ft2 1200 ft2

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, Manuallypressurized handwand / backpack 100 1.1 4.375E-6 lb 

ai/ft2 1200 ft2

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 Handled (A or 

gallons/day) / BW (80 kg).

4

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

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 hexythiazox. As no dermal hazard was 

identified, only incidental 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 rate1 Dose MOEs2

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 in 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 MOE2 Dose (mg/kg/day)3 MOE4

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 MOEs 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 method 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 Drift website for more information4. 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 drift 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 fields, 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 inhalation exposure scenarios. 

It is noted that the 0.19 lb ai/acre application rate for turf was modeled to estimate postapplication 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 

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 toxicity (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 its Federal Insecticide, Fungicide, and Rodenticide Act 

Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on 

March 2, 20105. The Agency is in the process of evaluating the SAP report and may, as 

appropriate, develop policies and procedures to identify the need for and, subsequently, the way 

to incorporate post-application inhalation exposure into the Agency's risk assessments. If new 

policies or procedures are developed, the Agency may revisit the need for a quantitative postapplication 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/2009/120109meeting.html
Page 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 Exposure/Risk Estimates

HED uses the term handlers to describe those individuals who are involved in the pesticide 

application process. HED believes that there are distinct job functions or tasks related to 

applications and exposures can vary depending on the specifics of each task. Job requirements 

(amount of chemical used in each application), the kinds of equipment used, the target being 

treated, and the level of protection used by a handler can cause exposure levels to differ in a 

manner specific to each application event. 

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 occupational 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 equipment; 

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 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 Table6”, 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 website7.

 

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

7 Available: http://www.epa.gov/pesticides/science/handler-exposure-data.html
Page 15 of 21

Area Treated or Amount Handled: 

Area treated or amount handled includes:

Aerial equipment: 350 acres orchard or field crops; 1200 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 large agribusiness and/or commercial applicators who may 

apply a product over a period of weeks (e.g., completing multiple applications for multiple 

clients within a region). 

For 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 necessary (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; therefore 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 handlers 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 aviation has changed dramatically over the past two 

decades. According the 2012 National Agricultural Aviation Association (NAAA) survey of 

their membership, the use of GPS for swath guidance in agricultural aviation has grown steadily 

from the mid 1990’s. Over the same time period, the use of human flaggers for aerial pesticide 

applications has decreased steadily from ~15% in the late 1990’s to only 1% in the most recent 

(2012) NAAA survey. The Agency will 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 are 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 Rate2

Area Treated 

or Amount 

Handled Daily3

Inhalation

Mitigation Level Dose (mg/kg/day)4 MOE5

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:

0.0049

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/Applicator
Page 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 Rate2

Area Treated 

or Amount 

Handled Daily3

Inhalation

Mitigation Level Dose (mg/kg/day)4 MOE5

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, Manuallypressurized Handwand, Broadcast Greenhouse 30 0.000625 lb 

ai/gallon 40 gallons 0.00000938 3,200,000

M/L/A, DF/WDG, Mechanicallypressurized 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 registered 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 reentry exposure). Such exposures may occur when workers enter previously treated areas to 

perform job functions, including activities related to crop production, such as scouting for pests 

or harvesting. Post-application exposure levels vary over time and depend on such things as the 

type of activity, the nature of the crop or target that was treated, the type of pesticide application, 

and the chemical’s degradation properties. In addition, the timing of pesticide applications, 

relative to harvest activities, can greatly reduce the potential for post-application exposure.

6.2.1 Occupational Post-application Inhalation Exposure/Risk Estimates

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-application activities in previously treated fields. These potential sources 

include volatilization of pesticides and resuspension of dusts and/or particulates that contain 

pesticides. The Agency sought expert advice and input on issues related to volatilization of 

pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel 

(SAP) in December 2009, and received the SAP’s final report on March 2, 20108. 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 assessment 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 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.

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

 

8 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
Page 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. Summary of Occupational Non-cancer Algorithms

Occupational Non-cancer Handler Algorithms

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

where:

E = exposure (mg ai/day),

UE = unit exposure (μg ai/lb ai),

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

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

The daily doses are calculated using the following formula:

where:

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

E = exposure (mg ai/day),

AF = absorption factor (dermal and/or inhalation), and

BW = body weight (kg).

Margin of Exposure: Non-cancer risk estimates for each application handler scenario are 

calculated using a Margin of Exposure (MOE), which is a ratio of the toxicological endpoint to 

the daily dose of concern. The daily dermal and inhalation dose received by occupational 

handlers are compared to the appropriate POD (i.e., NOAEL) to assess the risk to occupational 

handlers for each exposure route. All MOE values are calculated using the following formula:

where:

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

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

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