### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, 

### D.C. 20460



### Date:

Subject: February 08

, 2013 OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION



### Prothiocooazole. Occupational and R es i den t ial E xposure Assessment for Proposed Uses on Low Growing Berry Subgroup (except Strawberry), Bushberry

S ubgroup

, and Cuc urbi t Vegetables.

PC Code: 113961

Decision No.: 465457

Petition No.: 917677 DP Barcode: 0403739 Registration No.: 264-825 Regulator y Action: Section 3

Case No.: N / A Risk Assessment Type: OccupationaVResidential Exposure Assessment

TXRN o.: NA CAS No.: 178928-70 -6

40 CFR: § 180.626 MRIDNo.: NA



### From:

Through:

To:

Introduction Kristin Rury

, Biologist

# ~() .. __ __ Risk Assessment Branch 

# III

').,q 

# Q

Health Effects Division (7509P)

Barry O'K eefe, ORE Team Leader 

### 1.5 

## v 

# h

_ tl!¥

Risk Assessment Branch III

Health Effects Division (7509 P )

and

Scott Miller

## ~.**.** {,

Alexandra LaMay 

# (/,_L..-4'V'

Exposure Sc i ence Advisory Committ e (ExpoSAC) 

### I HED

Tony Kish, Risk Manager Fungicide Branch Registration Division (7505P)

The Regi s tration Division (RD) requested that the Health Effects Division (HED) conduct an

exposure and risk assessment for prothioconazole use on the low growing berry su bgroup (except strawberry), the bushberry subgroup, and cucurbit vegetables.

Page I of22

### It is HED policy to use the best available data t o assess exposure. Several sources of gene r ic

data were used in this assessment as surrogate data in the absence of chemical-specific data

, i ncluding: Pesticide Hand l ers Ex posure Database Version 1.1 (P HED 1.1 ); the Agricultural

Handler E xposure Task Force (AHETF) database; and the Agricultural Reentry Task Force (ARTF) database. Some of these data are proprietary, and subject to the data protection provisions of the Federal Insecticide, F ungicide, and Rodenticide Act (FIFRA).

Note: This memorandum was reviewed by th e Exposure Science Advisory Committee (ExpoSAC) on February 07, 2013

.

Page 2 of22Page 3 of 22 

### Table of Contents

1.0 Executive Summary

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

2.0 Risk Assessment Conclusions and Recommendations

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

2.1 Summary of Risk Estimates

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

2.2 Label Recommendations from Occupational Assessment

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

2.3 Data Deficiencies and Requirements

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

3.0 Hazard Characterization

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

4.0 Us e Profile

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

5.0 Residential Exposure and Risk Estimates

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

5.1 Spray Drift

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

5.3 Residential Bystander Post

- Application Inhalation Exposure

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

6.0 Occupational Exposure and Risk Estimates

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

6.1 Occupational Handler Exposure/Risk Estimates

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

6.2 Occupational Post

- Application Exposure/Risk Estimates

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

6.2.1 Occupational Post

- Application Inhalation Exposure/Risk Estimates

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

6.2.2 Occupational Post

- Application Dermal Exposure/Risk Estimates

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

- Cancer Algorithms

.................... 21Page 4 of 22



### 1.0 Executive Summary

Prothioconazole (2

- [2

- (1

- Chlorocyclpropyl)

- 3

- (2

- chlorophenyl)

- 2

- hydroxylpropyl]

- 1,2

- dihydro

3 H

- 1,2,4

- triazole

- 3

- thione) is a broad

- spectrum systemic fungicide used for the control of Ascomycetes, Basidiomycetes, and Deuteromycetes diseases in a variety of crops. It is in the

triazolinthione chemical class and is a de

- methylation

- inhibitor (DMI) which works through disruption of ergosterol biosynthesis (ergosterol is a precursor to Vitamin D 2 

### and is an important

compo nent of fungal cell walls). Prothioconazole is currently registered for use on barley; buckwheat; canola; chickpea; corn (field, sweet, seed, and pop); dry shelled peas and beans; lentils; millet; oats; oilseeds; peanut; rapeseed; rice; rye; soybeans; sug arbeets; triticale; wheat; and nursery seedlings of pines, conifers, and hardwoods. Additionally, prothioconazole is registered as a seed treatment for alfalfa, barley, beans, cereal grains, conifers, hardwoods, peas, pine, potato, rice, triticale, and wh eat.

Bayer Cropscience (Bayer) has proposed that use on the following crops be added to the Proline® 480 SC Fungicide (Proline) label: bushberries

, including Aronia berry, highbush and

lowbush blu e berry, Chilean guava, highbush cranberry, currant, elder berry, European barberry, gooseberry, edible honeysuckle, huckleberry, jostaberry, juneberry (Saskatoon berry), lingonberry, native currant, salal, and sea buckthron; low growing berries (excluding strawberry) including bearberry, billberry, cloudberry, cr anberry, muntries, and partridgeber ry ; and cucurbits

, including chayote; Chinese waxgourd; citron melon; cucumber; gerkin; edible gourd; Momordica spp, balsam apple, balsam pear, bittermelon, and Chinese cucumber; muskmelon, cantaloupe, pumpkin; squash, in cluding summer, winter, butternut, calabaza, hubbard, acorn, and spaghetti squash; and watermelon . Proline ( EPA Reg. No. 264

- 825 ) is a suspension concentrate (SC) broad

- spectrum fungicide and contains 41% of the active ingredient (ai) prothioconazole (4 lb ai/gallon).

Based on application rate and label information, exposure is expected to occur for short

- and

intermediate

- term durations. Chronic exposure is not expected for the propose d use patterns. Applicators and other handlers of Proline must wear long sleeved shirts, long pants, chemical resistant gloves made of waterproof material, shoes, and socks. The restricted entry interval (REI) is 12 hours.

Proposed Use Profile For the p roposed uses, Proline may be applied with ground, chemigation, airblast, or handheld equipment.

The proposed maximum application rate for cucurbits is 5.7 fl oz/A (0.18 lb ai/A) and applications may be made to the foliage or to the soil via drip/drench applications. A maximum of one soil application and two foliar applications are allowed per year. Repeat applications may

be made on a 5

- to 10

- day spray interval. A maximum of 17.1 fl oz/A (0.53 lb ai/A) may be applied per year. The pre

- harvest interv al (PHI) is 7 days. The proposed maximum application rate for bushberries is 5.7 fl oz/A (0.18 lb ai/A) and up to two applications may be made on a 7

- 10

- day spray interval. A maximum of 11.4 fl oz/A (0.35 lb ai/A) may be applied per year and

the PHI is 7 days. The proposed maximum application rate for low growing berries (except strawberry) is 5.0 fl oz/A (0.16 lb ai/A) and up to 2 foliar applications may be made per year on aPage 5 of 22



### 7

- to 10

- day spray interval. A maximum of 10.0 fl oz/A (0.31 lb ai/A) may be applied per year and the PHI is 45 days.

Hazard Concerns Prothioconazole breaks down into different compounds in different matrices. Of particular interest is prothioconazole

- desthio, a metabolite and degradate that is more toxic than the parent

compo und (and for which the registrant submitted a nearly complete toxicology database). The most protective quantitative hazard estimates are used in this risk assessment, based on a selection of endpoints from the prothioconazole

- desthio toxicology database.

A lthough the inhalation and dermal exposure scenarios have different points of departure (PoDs)

from different studies

, the toxicological effects (skeletal malformations) are the same. Therefore, the risk estimates are combined via the total margin of exposure (MOE) approach. The level of concern (LOC) for all exposure scenarios is an MOE less than 100, based on the standard uncertainty factors for intraspecies variation (10 X) and interspecies extrapolation (10X). Prothioconazole is classified as “Not likely to be Carcinogenic to Humans” based on the absence of significant tumor increases in two adequate rodent carcinogenicity studies.

Prothioconazole is classified as Toxic ity Category III for acute dermal and Category IV for primary eye and skin irritation. Additionally, prothioconazole

- desthio is classified as Toxicity Category IV for acute dermal and Categories III and IV for primary eye and skin irritation, respectively

.

Residential Exposure Residential exposures and risk are not assessed in this document because there are no existing or proposed residential uses.

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

- and intermediate

- term

non

- cancer dermal and inhalation MOEs are not of concern to HED (i.e., MOEs > 100) with the personal protective equipment (PPE) required on the Proline label (c hemical resistant gloves). With baseline attire, the combined dermal and inhalation MOEs for all proposed use sites ranged from 84 to 2,000. With gloves, the combined dermal and inhalation MOEs for all proposed use sites ranged from 170 to 7,600.

Occupational Post

-

Application On the day of application, the occupational dermal post

- application MOEs ranged from 210 to 6,300 and are not of concern to HED. The proposed REI of 12 hours is adequate.

Based on the Agency's current practices, a quantit ative non

- cancer occupational post

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

- applic ation inhalation exposure assessment for prothioconazole

.Page 6 of 22



### 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 ARTF database, are (1) subject to ethics review pursuant to 40 CFR 26, (2) have received that review, and (3) are compliant with applicable ethics requirements. For certain studies, the ethics review may hav e 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 risk estimates of c oncern associated with the proposed new uses of prothioconazole

.

HED recently waived the required subchronic inhalation toxicity study for prothioconazole (TXR# 0056563 ). The waiver was granted because all of the occupational inhalation MOEs are

> 1,000 using a conservative oral P o D

, and because prothioconazole has a low vapor pressure and low acute toxicity via the inhalation route of exposure. However, if the use pattern changes, this requirement may be reevaluated by HED.

2.1 Summary of Risk Estimates

Occupational Handlers With baseline attire, the combined dermal and inhalation MOEs for all proposed use sites ranged from 84 to 2,000. With gloves, the combined dermal and inhalation MOEs for all proposed use sites ranged from 170 to 7,600.

Occupational Post

-

Application On the day of application, the occupational dermal post

- application MOEs ranged from 210 to 6,300 and are not of concern to HED. The proposed REI of 12 hours is adequate.

2.2 Label Recommendations from Occupational Assessment

There are no recommendations for the proposed Proline label at this time.

2. 3 Data Deficiencies and Requirements

There are currently no deficiencies in the prothioconazole exposure database.

3 .0 Hazard Characterization

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

- exposure

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

- app

- exposure

- data.htmlPage 7 of 22



### Prothioconazole b reaks down into different compounds in different matrices. Of particular interest is prothioconazole

- desthio, a metabolite and degradate that is more toxic than the parent compound (and for which the registrant submitted a nearly complete toxicology datab ase). The most protective quantitative hazard estimates are used in this risk assessment, based on a selection of endpoints from the prothioconazole

- desthio toxicology database.

The toxicity database for prothioconazole is complete and provides sufficien t information to

determine whether prothioconazole poses a human health hazard

. The subchronic and chronic studies show that the target organs at the lowest observed adverse effect level (LOAEL) include the liver, kidney, urinary bladder, thyroid

, and blo od. In addition, the chronic studies showed body weight and food consumption changes, and toxicity to the lymphatic and gastrointestinal ( GI ) systems.

There are adequate data in the prothioconazole (including metabolites) database to characterize the pot ential for pre

- natal or post

- natal risks to infants and children: two

- generation reproduction studies in rats; developmental studies in rats and rabbits; and a developmental neurotoxicity study in rats. The effects seen in these studies suggest that offsp ring are more susceptible: offspring effects were seen at levels below the LOAELs for maternal toxicity and, in general, were of comparable or greater severity compared to the effects observed in adults. However, the

PoD for the most sensitive of these studies (the rabbit developmental toxicity) is lower than that of the other studies (2 mg/kg/day), and is based on effects observed in the fetus, not the parent. Therefore, the offspring are considered to be protected and t here is no need to retain the 10X FQPA database safety factor, (i.e. the 10X is reduced to 1X )

.

Acute Toxicity Prothioconazole has low acute toxicity by oral, dermal, and inhalation routes. It is not a dermal sensitizer, or a skin or eye irritant. Proth ioconazole

- D esthio also has low acute toxicity by oral, dermal, and inhalation routes. It is not a dermal sensitizer, or a skin irritant, but it is a slight eye

irritant. The acute toxicity profiles of prothioconazole and its metabolite prothioconazole

d esthio are summarized in Table s 3.1 and 3.2

.

Table 3.1. Acute Toxicity Profile for Prothioconazole Technical.

Guideline

Number Study Type MRID Number Results Toxicity Category

870.1100 Acute Oral 46246230 LD 50 >= 6200 mg/kg (M, F) IV

870.1200 Acute Dermal 46246244 LD 50 >= 2000 mg/kg (M, F) III

870.1300 Acute Inhalation 46246246 LC 50 >= 4.99 mg/L (M, F) IV

870.2400 Primary Eye Irritation 46246249 Not an irritant IV

870.2500 Primary Skin Irritation 46246302 Not an irritant IV

870.2600 Dermal Sensitization 46246305 Not a sensitizer NA a

a NA = Not Applicable.Page 8 of 22

Table 3.2. Acute Toxicity Profile for Prothioconazole

- Desthio Technical.

Guideline

Number Study Type MRID Number Results Toxicity Category

870.1100 Acute Oral 46246231 LD 50 = ~2806 mg/kg (M, F) III

870.1200 Acute Dermal 46246242 LD 50 = 2235 mg/kg (Males)

LD 50 = 3459 mg/kg (Females) III

870.1300 Acute Inhalation 46246243 LD 50 >= 5000 mg/kg (M,F) IV

870.2400 Primary Eye Irritation 46246247 LC 50 >= 5.077 mg/L (M,F) IV

870.2500 Primary Skin Irritation 46246250 Slight irritant (iritis, discharge) III

870.2600 Dermal Sensitization 46246250 Not an irritant NA a

a NA = Not Applicable.



### Toxicological P o Ds Used for Risk Assessment

The relevant exposure scenarios for the proposed prothioconazole uses are short

- and

intermediate

- term dermal and inhalation exposure during occupational handling activities . For

the short

- and intermediate

- term dermal exposure scenarios, a quantitative hazard estimate of 30 mg/kg/day (NOAEL) was selected from the dermal developmental toxicity study in the rat, based on an increased incidence of supernumerary rib (14 th 

### rib) at the LOAEL (100 mg/kg/day). A dermal absorption factor was not applied because the study was route specific. F or the short

and intermediate

- term inhalation exposure scenarios, a quantitative hazard estimate of 2 mg/kg/day (NOAEL) was selected from the developmental toxicity study in the rabbit, based on arthrogryposis and multiple malformations at the LOAEL (10 m g/kg/day). Because the developmental study in the rabbit was an oral study, an inhalation absorption factor of 100% was applied to the exposure estimates; oral and inhalation toxicity is assumed to be equivalent.

A lthough the inhalation and dermal expo sure scenarios have different PoDs from different

studies

, the toxicological effects (skeletal malformations) are the same. Therefore, the risk

estimates are combined via the total MOE approach. The LOC for all exposure scenarios is an

MOE of less than 1 00, based on the standard uncertainty factors for intraspecies variation (10X) and interspecies extrapolation (10X). Prothioconazole is classified as “Not likely to be Carcinogenic to Humans” based on the absence of significant tumor increases in two adeq uate rodent carcinogenicity studies. The endpoints and doses selected for risk assessment purposes

are summarized in Table 3 .4

.

Table 3.4. Summary of Toxicological Doses and Endpoints for Prothioconazole.

Exposure

(Scenario) PoD Uncertainty and FQ PA Safety

Factors RfD/PAD/

LOC Study and Toxicological Effects

Dermal Short

- (1

- 30 days) and

Intermediate

- (1

- 6 months)

Term NOAEL = 30

mg/kg/day UF A =10X

UF H =10X

FQPA SF =

1X Occupational

LOC for MOE =

100 Dermal Developmental Study in Rats

LOAEL = 100 mg/kg/day based on an increased incidence of supernumerary rib (14th rib)

.Page 9 of 22

Table 3.4. Summary of Toxicological Doses and Endpoints for Prothioconazole.

Exposure

(Scenario) PoD Uncertainty and FQ PA Safety

Factors RfD/PAD/

LOC Study and Toxicological Effects

Inhalation Short

- (1

- 30 days) and

Intermediate

- (1

- 6 months)

Term NOAEL =

2.0 mg/kg/day UF A =10X

UF H =10X

FQPA SF =

1X Occupational

LOC for MOE =

100 Developmental Study in Rabbits

LOAEL = 10 mg/kg/day based on structural alterations including malformed vertebral body and ribs, arthrogryposis, and multiple

malformations.

Cancer (oral, dermal, inhalation) Classification: “Not likely to be Carcinogenic to Humans” based on the absence of significant

tumor increases in two adequate rodent carcinogenicity studies.

PoD = Point of Departure, a data point (or 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 sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. LOC = Level Of Concern. MOE = Margin Of Exposure.



### Body Weight Since the dermal and inhalation PODs are based on developmental a nd/or fetal effects, the body weight appropriate for dermal and inhalation assessments is 69 kg.

Absorption Factor Since the dermal POD is based on a route specific study, a dermal absorption factor is not

needed. Since the inhalation POD is based on an oral study, the inhalation absorption is assumed to be equivalent to the oral dose.

4 .0 Use Profile

The proposed uses of prothioconazole are included in Table 4.0. Aerial application is not permitted for the proposed use sites.

Table 4.0. Summary of D irections for the Proposed Uses of Prothioconazole

Crop Application

Method(s) Maximum Application

Rate Number of Applications,

Maximum Seasonal Application

Rate and RTI PHI

fl oz/A lb ai/A

(lb ai/gallon) 1 lb ai/A days

PROLINE ® 400 SC Fungicide

Bushberry Subgroup Ground, Airblast,

Chemigation,

Handheld 5.7 0.1 8

(0.018) 2 applications/year,

11.4 fl oz/year (0.35 lb ai/A),

RTI = 7

- 10 day interval 7

Low growing berry, except strawberry Ground,

Chemigation,

Handheld 5.0 0.16

(0.016) 2 applications/year,

10.0 fl oz/year (0.31 lb ai/A),

RTI = 7

- 10 day interval 45

Cucurbits Ground,

Chemigation, 5.7 0.1 8 1 soil application, 2 foliar applications, 7Page 10 of 22

Table 4.0. Summary of D irections for the Proposed Uses of Prothioconazole

Crop Application

Method(s) Maximum Application

Rate Number of Applications,

Maximum Seasonal Application

Rate and RTI PHI

Handheld

(Foliar and Soil Directed/Drench) ( 0.018) 17.1 fl oz/year (0.53 lb ai/A),

RTI = 5

- 10 day interval

1 Handheld application rates were calculated based on a minimum mixture of 10 gallons per acre as stated on the Proline (EPA Reg. No. 264

- 825) label. For example, for low growing berries, the lb ai/gallon application rate was calculated as 5.0 fl oz/A x 4 lb ai/gal ÷ 128 fl oz x 10 gal/A = 0.016 lb ai/gal.



### 5 .0 Residential Exposure and Risk Estimates

There are no proposed residential uses at this time and there are currently no registered residential uses of prothioconazole.

5

. 1 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 prothioconazole

. The Agency has been working with the Spray Drift Task Force, EPA Regional Offices

, and State Lead Agencies for pesticide regula tion and other parties to develop the best spray drift management practices (see the Agency’s Spray Drift website for more information 2



### . The Agency has 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.

5

. 3 Residential Bystander Post

- Application Inhalation Exposure

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

- application inhalation exposure assessment was not performed for prothioconazole at this time primarily because of the low acute inhalation toxicity (Toxicity Category IV), low vapor pressure ( 3.00 × 1 0 - 9 

### at 20oC ), and the low proposed use rate (0. 18 lb ai/A). 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 Fe deral Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 3



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

- application inhalation exposure into the Agency's risk assessments. If new policies or procedures are developed, the Agency may

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

3 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.htmlPage 11 of 22



### revisit the need for a quantitative post

- application inhalation exposure assessment for prothioconazole

.

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

app lication 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 u sed, 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 technique s 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 liquids for chemigation ap plication; Mixing/loading liquids for groundboom application; Mixing/loading liquids for airblast application (bushberries only); Applying liquids via groundboom; Applying liquids via airblast (bushberries only); Mixing/loading/applying liquids via mech anically pressurized handgun (foliar); and Mixing/loading/applying liquids via mechanically pressurized handgun (soil drench).

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 : Proposed application rates are listed in Table 4.0.

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 regis trant

- 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

ass essment, known as “unit exposures”, are outlined in the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table 4 

### ”, which, along with additional information on HED policy on use of surrogate data, including descriptions of the various source s, can be found at the Agency website 5



### .

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

- exposure

- table.pdf

5 Available: http://www.e pa.gov/pesticides/science/handler

- exposure

- data.htmlPage 12 of 22



### Area Treated or Amount Handled : Based on HED ExpoSAC Policy 9.1, the amount treated or handled per day was assumed to be: 350 acres for mixing/loading for chemigation application; 80 acres for mixing/loading for groundboom application; 40 acres for mixing/loading for airblast application (bushberries only); 80 acres for applying with groundboom equipment; 40 acres for applying with airblast equipment (bushberries only); and
1,000 gallons for mechanically pressurized handgun application.

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 chemi cal 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).

Fo r prothioconazole , based on the registered and proposed use s
, short

- and intermediate

- term

exposures are expec ted. Prothioconazole is registered for use on a number of crops for multiple applications; however, the proposed uses restrict applications to on ce or twice per growing year. Additionally, since the same endpoint and PoD were selected for short

- and intermediate

- term durations, short

- term exposure and risk estimates are considered to be protective of intermediate

term exposure and risk.

Mitigat ion/Personal Protective Equipment : Estimates of dermal and inhalation exposure were calculated for various levels of PPE. Results are presented for “baseline,” defined as a single layer of clothing consisting of a long sleeved shirt, long pants, shoes pl us socks, no protective gloves, and no respirator, as well as baseline with various levels of PPE as necessary (e.g., gloves, respirator, etc). The prothioconazole product labels direct mixers, loaders, applicators

and other handlers to wear long sleeved shirts, long pants, shoes, socks, and chemical resistant gloves

.

Occupational Handler Non

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

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

.

Combi ning Exposures/ Risk Estimates : Dermal and inhalation risk estimates were combined in this assessment, since the toxicological effects for these exposure routes were similar. Dermal and inhalation risk estimates were combined using the following formula:

Total MOE = 1 ÷ ( (1/Dermal MOE) + (1/Inhalation MOE) )Page 13 of 22



### Summary of Occupational Handler Non

- C ancer Exposure and Risk Estimates With baseline attire, the combined dermal and inhalation MOEs for all proposed use sites ranged from 84 to 2,000. With gloves, the combined dermal and inhalation MOEs for all proposed use sites ranged from 170 to 7,600.Page 14 of 22

Table 6 .1. 1

. Occupational Handler Non

- C ancer Exposure and Risk Estimates for Prothioconazole at Baseline PPE

.

Exposure Scenario Crop or Target Dermal Unit

Exposure ( μ g/lb ai) 1 Inhalation Unit

Exposure ( μ g/lb ai) 1 Maximum

Application

Rate 2 Area

Treated or

Amount

Handled Daily 3 Dermal Inhalation Total

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

Mixer/Loader

Mixing/Loading Liquids for Chemigation Application Bushberries,

Cucurbits 220 0.219 0.18 lb ai/A 350 Acres 0.201 150 0.00020 10,000 150

Low Growing Berry (except Strawberry) 220 0.219 0.16 lb ai/A 350 Acres 0.178 170 0.00018 11,000 170

Mixing /Loading Liquids

for Groundboom Application Bushberries,

Cucurbits 220 0.219 0.18 lb ai/A 80 Acres 0.046 650 0.000046 44,000 640

Low G rowing Berry (except Strawberry) 220 0.219 0.16 lb ai/A 80 Acres 0.041 730 0.000041 49,000 720

Mixing /Loading Liquids for Airblast Application Bushberries 220 0.219 0.18 lb ai/A 40 Acres 3.19 1,300 0.0000229 87,000 1,300

Applicator

Applying Sprays

– Groundboom Bushberries,

Cucurbits 78.6 0.34 0.18 lb ai/A 80 Acres 0.016 1,800 0.000071 28,000 1,700

Low Growing Berry (except Strawberry) 78.6 0.34 0.16 lb ai/A 80 Acres 0.015 2,100 0.000063 32,000 2,000

Applying Sprays

– Airblast Bushberries 1,770 4.17 0.18 lb ai/A 40 Acres 0.184 160 0.000491 4,100 150

Mixer/ L oader/Applicator

Mixing/Loading Applying Sprays with Mechanically Pressurized Handgun (foliar) Bushberries,

Cucurbits 1300 3.9 0.018

lb ai/Gal 1,000

Gallons 0.34 88 0.00102 2,000 84

Low Growing Berry (except Strawberry) 1300 3.9 0.016

lb ai/Gal 1,000

Gallons 0.29 100 0.00088 2,300 96

Mixing/Loading Applying Sprays with Mechanically Pressurized Handgun (Soil Drench) Cucurbits 1300 3.9 0.018

lb ai/Gal 1,000

Gallons 0.34 89 0.00101 2,000 85

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” ( 3/2012 ); Level of mitigation: Baseline.Page 15 of 22 2 Based on registered or proposed label (Reg. No. 264

- 825 ).

3 Exposure Science Advisory Council Policy #9.1.

4 Dermal Dose = Dermal Unit Exposure ( μ g/lb ai) × Conversion Factor (0.001 mg/ μ g) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) ÷ BW ( 69 kg).

5 Dermal MOE = Dermal NOAEL (mg/kg/day) ÷ Dermal Dose (mg/kg/day). Dermal NOAEL = 30 mg/kg/day.

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

7 Inhalati on MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). Inhalation NOAEL = 2 mg/kg/day.

8 Total MOE = 1 ÷ (1/Dermal MOE + 1/Inhalation MOE).

Table 6.1. 2

. Occupational Handler Non

- C ancer Exposure and Risk Estimates for Prothioconazole with Label

- Specified PPE (Gloves)

.

Exposure Scenario Crop or Target Dermal Unit

Exposure ( μ g/lb ai) 1 Inhalation Unit

Exposure ( μ g/lb ai) 1 Maximum

Application

Rate 2 Area

Treated or

Amount

Handled Daily 3 Dermal Inhalation Total

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

Mixer/Loader

Mixing/Loading Liquids for Chemigation Application Bushberries,

Cucurbits 37.6 0.219 0.18 lb ai/A 350 Acres 0.034 870 0.00020 10,000 800

Low Growing Berry (except Strawberry) 37.6 0.219 0.16 lb ai/A 350 Acres 0.031 980 0.00018 11,000 900

Mixing/Loading Liquids

for Groundboom Application Bushberries,

Cucurbits 37.6 0.219 0.18 lb ai/A 80 Acres 0.0078 3,800 0.000046 44,000 3,500

Low G rowing Berry (except Strawberry) 37.6 0.219 0.16 lb ai/A 80 Acres 0.0070 4,300 0.000041 49,000 4,000

Mixing/Loading Liquids for Airblast Application Bushberries 37.6 0.219 0.18 lb ai/A 40 Acres 0.00393 7,600 0.0000229 87,000 7,000

Applicator

Applying Sprays

– Groundboom Bushberries,

Cucurbits 16.1 0.34 0.18 lb ai/A 80 Acres 0.0034 8,900 0.000071 28,000 6,800

Low Growing Berry (except Strawberry) 16.1 0.34 0.16 lb ai/A 80 Acres 0.0030 10,000 0.000063 32,000 7,600

Applying Sprays

– Airblast Bushberries 1590 4.71 0.18 lb ai/A 40 Acres 0.165 180 0.000491 4,100 170

Mixer/ L oader/Applicator

Mixing/Loading Applying Sprays with Mechanically Bushberries,

Cucurbits 390 3.9 0.018

lb ai/Gal 1,000

Gallons 0.102 290 0.00102 2,000 250Page 16 of 22

Table 6.1. 2

. Occupational Handler Non

- C ancer Exposure and Risk Estimates for Prothioconazole with Label

- Specified PPE (Gloves)

.

Exposure Scenario Crop or Target Dermal Unit

Exposure ( μ g/lb ai) 1 Inhalation Unit

Exposure ( μ g/lb ai) 1 Maximum

Application

Rate 2 Area

Treated or

Amount

Handled Daily 3 Dermal Inhalation Total

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

Pressurized Handgun (foliar) Low Growing

Berry (except Strawberry) 390 3.9 0.016

lb ai/Gal 1,000

Gallons 0.088 340 0.00088 2,300 300

Mixing/Loading Applying Sprays with Mechanically Pressurized Handgun (Soil Drench) Cucurbits

390 3.9 0.018

lb ai/Gal 1,000

Gallons 0.101 300 0.00101 2,000 260

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” ( 3/2012 ); Level of mitigation: Gloves, No Respirator

. 2 Based on registered or proposed label (Reg. No. 264

- 825 ).

3 Exposure Science Advisory Council Policy #9.1.

4 Dermal Dose = Dermal Unit Exposure ( μ g/lb ai) × Conversion Factor (0.001 mg/ μ g) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) ÷ BW ( 69 kg).

5 Dermal MOE = Dermal NOAEL (mg/kg/day) ÷ Dermal Dose (mg/kg/day). Dermal NOAEL = 30 mg/kg/day.

6 Inhalation Dose = Inhalation Unit Exposure ( μ g/lb ai) × Conversion Factor (0.001 mg/ μ g) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/d ay) ÷ BW ( 69 kg).

7 Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). Inhalation NOAEL = 2 mg/kg/day.

8 Total MOE = 1 ÷ (1/Dermal MOE + 1/Inhalation MOE).Page 17 of 22



### 6

. 2 Occupational Post

- A pplication 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 previ ously 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 activity, the nature of the c rop 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

- A pplication Inhalation Exposure/Risk Estimates

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

- application inhalation exposure assessment was not performed for prothioconazole at this time primarily because of the low acute inhalation toxicity (Toxicity Category IV), low vapor pressure ( 3.00 × 10 - 9 

### mm Hg at
20oC ), and the low proposed use rate (0. 18 lb ai/A). However, there are multiple potential sources of post

- application i nhalation 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 e xpert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 6



### . 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 occup ational 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 prothioc onazole

.

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 pesticid es outdoors is likely to result in higher exposure than post

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

- application inhalation exposure scenarios.

6

. 2 .2 Occupational Post

- A pplication Dermal Exposure/Risk Estimates

Occupational Post

- A pplication Dermal Exposure Data and Assumptions A series of assumptions and exposure factors served as the basis for completing the occupational

post

- application risk assessments. Each assumption and factor is detailed below on an individual

basis.

6 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.htmlPage 18 of 22



### Exposure Duration: Based on the proposed prothioconazole use pattern for bushberries, low growing berries, and cucurbits, post

- application exposure to prothioconazole is ex pected to be

short

- , and intermediate

- term. The use pattern indicates that repeated applications are allowed,

and hand

- setting irrigation and scouting may allow for continuous exposure. Additionally, the

short

- and intermediate

- term POD are the same for assessing short

- and intermediate

- term exposure to prothioconazole; therefore, the assessment is projective of both exposure durations.

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

application exposure. Sources of generic post

- application data, used as surrogate data in the

absence of chemical

- specific data, are derived from ARTF exposure monitoring studies, and, as proprietary data, are subject to the data protection provisions of FIFRA. The standard values recommended for use in predicting post

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

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



### .

Table 6.2.2

. 1. Proposed Representative Crops and Transfer Coefficient Groups

.

Proposed Crops Policy Crop Group Categor ies Transfer

Coefficien ts Activities

Bushberries Vine/Trellis and Berry, low 70 Hand weeding

230 Transplanting

640 Scouting, Hand pruning, Hand weeding, Bird control, Frost control

1100 Hand harvesting (low crop height, full foliage)

1400 Hand harvesting (high crop height, full foliage)

1900 Hand set irrigation

Cucurbits Vegetable, cucurbit 90 Scouting, Hand weeding, Thinning fruit, Hand pruning, Turning, Training

230 Transplanting, Mechanically assisted harvesting

550 Hand harvesting, Turning

1900 Hand set irrigation

Low Growing Berries Berry, low 70 Hand pruning (shears), Hand weeding

230 Transplanting

1100 Hand harvesting (raking), scouting



### Application Rate: See Section 4.0 for the proposed maximum application rates.

Exposure Time : The average occupational workday is assumed to be 8 hours.

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

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

- app

- exposure

- data.htmlPage 19 of 22



### Dislodgeable Foliar Residues : A dislodgeable foliar residue study on four crops is available for prothioconazole (MRID 470026

- 01, D335477, S. Winfield, 12/31/2007) . The study results for

DFR values are summarized below in Table 6.2.2.2

.

In the absence of chemical

- specific DFR data, HED assumes a default dissipation rate of 10% per day, and that a default fraction of the applied ai is available on the foliage on the day of application ( i.e. , 2 5 %) when calculating DFR estimates (which in turn are used in postapplication exposure estimates). However, the chemical

- specific DFR data demonstrated that total prothioconazole (prothioconazole and prothioconazole

- desthio combined) dissipate mor e quickly than 10% per day, and that the fraction of applied ai available on the foliage as a percent of the application rate, can be 2

- fold lower than 2 5 %. These DFR data were used to calculate DFR estimates (for use in postapplication exposure estimates ) for dry beans (C 0 

### = 0.671 μg/cm 2 

### ) , and were extrapolated to those crops for which no DFR data are available.

In order to estimate DFRs for the crops prothioconazole is proposed for use on, a n average of the

maximum DFR value s was used from the DFR studies conducted on each crop. Although uncertainties are introduced into the assessment when crop

- specific residues are used to estimate dissipation parameters, it is believed to be more realistic than using default assumptions.

Table 6.2

. 2.2 . Results of HED Analyses

– Calculated Total Prothioconazole 1

. Crop Location

(state) R 2 Predicted Residues on Day

0 (% of appl. rate) Dissipation

(% per day) Half life

(days) Predicted Day 0

T otal

P rothioconazole ( μ g/cm 2 ) 1

dry beans Oregon 0.83 17% 66% 0.65 0.343

Washington 0. 83 33 % 67% 0.62 0.671
soybeans Nebraska N/A N/A N/A N/A N/A

Minnesota 0.95 16% 71% 0.56 0.255
sugar beets Minnesota 0.91 12% 38% 1.4 0.233
peanuts Florida 0.85 9.0 % 3 8 % 1.5 0.185

Georgia 0.97 9.0 % 64 % 0.68 0.183

1 N/A = Not Available; all residue values measured were <LOQ on Day 0 in the soybean study.



### Occupational Post

- A pplication Non

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

- cancer exposure and dose for occupational post

- application workers can be found in Appendix A

.

Occupational Post

- A pplication Non

- Cancer Dermal Risk Estimates On the day of application, the occupational dermal post

- application MOEs ranged from 2 1 0 to

6

, 3 00 and are not of concern to HED. The results of the occupational post

- application exposure assessment using chemical

- specific DFR data are presented in Table 6.2.2.3. These estimates can be considered conservative because the highest measured DFR value was extrapolated to all crops. A more refined assessment would match measured available DFR values with similar

crops.Page 20 of 22

Table 6.2.2. 3. Post

- A pplication Exposure and Risk for Prothioconazole.

Crop Activity Transfer

Coefficient a
(cm 2 /hr) DAT b DFR c (μg/cm 2 ) Short

- Term

Daily

Dermal

Dose d
(mg/kg/day) MOE e

Bushberries Hand weeding 70 0 (12 hours) 0. 664 0.00539 5,600

Transplanting 230 0 (12 hours) 0. 664 0.0177 1,700

Scouting, Hand pruning, Hand weeding, Bird control, Frost control 640 0 (12 hours) 0. 664 0.0493 610

Hand harvesting (low crop height,

full foliage) 1100 0 (12 hours) 0. 664 0 .0847 350

Hand harvesting (high crop height,

full foliage) 1400 0 (12 hours) 0. 664 0.108 280

Hand set irrigation 1900 0 (12 hours) 0. 664 0.146 210

Cucurbits Scouting, Hand weeding, Thinning

fruit, Hand pruning, Turning,

Training 90 0 (12 hours) 0. 664 0.00693 4,300

Transplanting, Mechanically assisted harvesting 230 0 (12 hours) 0. 664 0.0177 1,700

Hand harvesting, Turning 550 0 (12 hours) 0. 664 0.0423 710

Hand set irrigation 1900 0 (12 hours) 0. 664 0.146 210

Low Growing

Berries Hand pruning (shears), Hand weeding 70 0 (12 hours) 0.59 0.00479 6,300

Transplanting 230 0 (12 hours) 0.59 0.0157 1,900

Hand harvesting (raking), scouting 1100 0 (12 hours) 0.59 0.0752 400



### a Transfer coefficients and associated activities from ExpoSAC SOP No. 003.1 “Agricultural Transfer Coefficients

, ” 8/17/2000.

b DAT = Days after treatment needed to reach the LOC of 100; DAT 0 = the day of treatment, after sprays have dried; assumed

to be a pproximately 12 hours.

c DFR (μg/cm 2 ) based on MRID 47002601 (See Table 6.2.2.2)

. d Daily Dose = [(DFR x TC x Dermal absorption x 8

- hr Exposure Time)] / [(CF: 1000 μg/mg) x ( 69 kg Body Weight)] ( D ermal absorption factor = 100 % ).

e M OE = NOAEL/Daily Dose (Short

- and Intermediate

- T erm Dermal NOAEL = 30 mg/kg/day 

### )

.

Restricted Entry Interval The REI specified on the proposed label is based on the acute toxicity of prothioconazole.

Prothioconazole is classified as Toxicity Category III via the dermal route and Toxicity Category

IV for skin irritation potential. It is not a skin sensitizer. Prothioconazole

- D esthio is classified as Toxicity Category III via the dermal route and Toxicity Category III for skin irritation potential and is a slight skin irritant. Short

- and intermediate

- term post

- application risk estimates were not a concern on day 0 (12 hours followin g application) for all post

- application activities. Under 40 CFR 156.208 (c) (2) (iii), active ingredient’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 prothioconazole

.Page 21 of 22



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

- C ancer Algorithms

Occupational Non

- C ancer 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:

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

- C ancer risk estimates for each application handler scenario are

calculated usin g 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 a re compared to the appropriate POD ( i.e.

, NOAEL) to assess the risk to occup ational 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)

.Page 22 of 22



### Occupational Non

- C ancer Post

- A pplication Algorithms

Potential daily exposures for occupational post

- application workers are calculated using the following formulas:

where:

E = e xposure (mg ai/day),

DFR t 

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

### ) = AR * F * (1

- D) t 

### from the

prothioconazole dry beans study (Washington; MRID 470026

- 01); 0.671 μg/cm 2



### , AR = a pplication r ate ( 0.182 lb ai/acre),

F = fraction of ai retained on foliage 33 % (unitless),

D = fraction of residue that dissipates daily or 67 % (unitless), and

t = number of days after application day (days)

. TC = t ransfer coefficient (cm 2 

### /hr),

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

- C ancer 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 worker s 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 (unitless),

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

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