UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

Date: 

Subject: 

February 08, 2013 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

Prothiocooazole. Occupational and Residential Exposure Assessment for 

Proposed Uses on Low Growing Berry Subgroup (except Strawberry), Bushberry 

Subgroup, and Cucurbit Vegetables. 

PC Code: 113961 

Decision No.: 465457 

Petition No.: 917677 

DP Barcode: 0403739 

Registration No.: 264-825 

Regulatory Action: Section 3 

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

TXRNo.: NA CAS No.: 178928-70-6 

MRIDNo.: NA 40 CFR: § 180.626 

From: 

Through: 

To: 

Introduction 

Kristin Rury, Biologist ~() .. __ __ 

Risk Assessment Branch III ').,q Q 

Health Effects Division (7509P) 

Barry O'Keefe, ORE Team Leader 1.5 h_tl!¥ v 

Risk Assessment Branch III 

Health Effects Division (7509P) 

and 

Scott Miller ~.. {, 

Alexandra LaMay (/,_L..-4'V' 

Exposure Science Advisory Committ e (ExpoSAC) I HED 

Tony Kish, Risk Manager 

Fungicide Branch 

Registration Division (7505P) 

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

exposure and risk assessment for prothioconazole use on the low growing berry subgroup 

(except strawberry), the bushberry subgroup, and cucurbit vegetables. 

Page I of22 
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; 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, Fungicide, and Rodenticide Act (FIFRA). 

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

(ExpoSAC) on February 07, 2013 . 

Page 2 of22 
Page 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 Use 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.................... 21
Page 4 of 22

1.0 Executive Summary

Prothioconazole (2-[2-(1-Chlorocyclpropyl)-3-(2-chlorophenyl)-2-hydroxylpropyl]-1,2-dihydro3H-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 D2 and is an important 

component 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; sugarbeets; 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 wheat. 

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 blueberry, Chilean guava, highbush cranberry, currant, elderberry, 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, cranberry, muntries, and partridgeberry; 

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, including 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 proposed 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 proposed 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 interval (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 a 
Page 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 

compound (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.

Although 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 (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 adequate rodent carcinogenicity studies.

Prothioconazole is classified as Toxicity 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 (chemical 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 quantitative 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-application 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 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 risk estimates of concern 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 PoD, 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.html
Page 7 of 22

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 

compound (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.

The toxicity database for prothioconazole is complete and provides sufficient 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 blood. 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 potential 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 offspring 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 there 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. Prothioconazole-Desthio 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 prothioconazoledesthio are summarized in Tables 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 LD50 >= 6200 mg/kg (M, F) IV

870.1200 Acute Dermal 46246244 LD50 >= 2000 mg/kg (M, F) III

870.1300 Acute Inhalation 46246246 LC50 >= 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 NAa

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 LD50 = ~2806 mg/kg (M, F) III

870.1200 Acute Dermal 46246242 LD50 = 2235 mg/kg (Males)

LD50 = 3459 mg/kg (Females) III

870.1300 Acute Inhalation 46246243 LD50 >= 5000 mg/kg (M,F) IV

870.2400 Primary Eye Irritation 46246247 LC50 >= 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 NAa

a NA = Not Applicable.

Toxicological PoDs 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 (14th rib) at the LOAEL (100 mg/kg/day). A 

dermal absorption factor was not applied because the study was route specific. For the shortand 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 mg/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. 

Although the inhalation and dermal exposure 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 100, 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 adequate 

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 FQPA 

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

UFA=10X

UFH=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 FQPA 

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

UFA=10X

UFH=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. UFA = extrapolation from animal to human (interspecies). UFH = 

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 and/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 Directions 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

0.18

(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 0.18

1 soil application, 2 foliar 

applications, 7
Page 10 of 22

Table 4.0. Summary of Directions 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 regulation and other parties to develop the best spray drift 

management practices (see the Agency’s Spray Drift website for more information2. 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 × 10

-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 Federal 

Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, 

and received the SAP’s final report on March 2, 20103. 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.html
Page 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 

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 liquids for chemigation application;

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 mechanically 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 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 Table4”, 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 website5.

 

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

5 Available: http://www.epa.gov/pesticides/science/handler-exposure-data.html
Page 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 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 prothioconazole, based on the registered and proposed uses, short- and intermediate-term

exposures are expected. Prothioconazole is registered for use on a number of crops for multiple 

applications; however, the proposed uses restrict applications to once 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 intermediateterm exposure and risk. 

Mitigation/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 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 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-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 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-Cancer 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-Cancer Exposure and Risk Estimates for Prothioconazole at Baseline PPE. 

Exposure Scenario Crop or 

Target

Dermal Unit 

Exposure (μg/lb 

ai)1

Inhalation Unit 

Exposure (μg/lb 

ai)1

Maximum 

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inhalation Total

Baseline Baseline Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE8

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 Growing 

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/Loader/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 (μg/lb ai) × Conversion Factor (0.001 mg/μg) × 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 (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) ÷ 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).

Table 6.1.2. Occupational Handler Non-Cancer Exposure and Risk Estimates for Prothioconazole with Label-Specified PPE (Gloves). 

Exposure Scenario Crop or 

Target

Dermal Unit 

Exposure (μg/lb 

ai)1

Inhalation Unit 

Exposure (μg/lb 

ai)1

Maximum 

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inhalation Total

Gloves Baseline Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE8

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 Growing 

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/Loader/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 2,000 250
Page 16 of 22

Table 6.1.2. Occupational Handler Non-Cancer Exposure and Risk Estimates for Prothioconazole with Label-Specified PPE (Gloves). 

Exposure Scenario Crop or 

Target

Dermal Unit 

Exposure (μg/lb 

ai)1

Inhalation Unit 

Exposure (μg/lb 

ai)1

Maximum 

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inhalation Total

Gloves Baseline Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE8

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 (μg/lb ai) × Conversion Factor (0.001 mg/μg) × 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 (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) ÷ 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-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 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 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, 20106. 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 prothioconazole.

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.

6.2.2 Occupational Post-Application Dermal Exposure/Risk Estimates

Occupational Post-Application Dermal Exposure Data and Assumptions

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

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

basis.

 

6 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
Page 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 expected 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 postapplication 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 37” which, along with 

additional information about the ARTF data, can be found at the Agency website8.

Table 6.2.2.1. Proposed Representative Crops and Transfer Coefficient Groups.

Proposed Crops Policy Crop Group 

Categories

Transfer 

Coefficients 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.html
Page 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., 25%) 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 more 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 25%. These DFR data were used to calculate DFR 

estimates (for use in postapplication exposure estimates) for dry beans (C0 = 0.671 μg/cm2), 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, an average of the 

maximum DFR values 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 Prothioconazole1. 

Crop Location 

(state)

R

2 Predicted 

Residues on Day 

0 (% of appl. 

rate)

Dissipation 

(% per day)

Half life 

(days)

Predicted Day 0 

TotalProthioconazole 

(μg/cm2)

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% 38% 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-Application 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-Application Non-Cancer Dermal Risk Estimates

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 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-Application Exposure and Risk for Prothioconazole.

Crop Activity

Transfer

Coefficienta

(cm2/hr)

DATb DFRc

(μg/cm2)

Short-Term

Daily 

Dermal 

Dosed

(mg/kg/day)

MOEe

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 approximately 12 hours. 

c DFR (μg/cm2) 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)] (Dermal 

absorption factor = 100%). 

e MOE = NOAEL/Daily Dose (Short- and Intermediate-Term 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-Desthio 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 following 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-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).
Page 22 of 22

Occupational Non-Cancer Post-Application Algorithms

Potential daily exposures for occupational post-application workers are calculated using the 

following formulas:

where:

E = exposure (mg ai/day),

DFRt = dislodgeable foliage residue on day "t" (μg/cm2) = AR * F * (1-D)tfrom the 

prothioconazole dry beans study (Washington; MRID 470026-01); 0.671μg/cm2,

AR = application rate (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 = transfer coefficient (cm2/hr),

ET = exposure time (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 = exposure (mg ai/day),

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

BW = body weight (kg).

Margin of Exposure: Non-Cancer risk estimates for each scenario are calculated using a Margin 

of Exposure (MOE), which is a ratio of the toxicological endpoint to the daily dose of concern. 

The daily dermal dose received by occupational post-application workers is compared to the 

appropriate POD (i.e., NOAEL) to assess the risk to occupational post-application workers. All 

MOE values 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).