### 1 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION 

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

PC Code: 113961 DP Barcode: D 427289 Dat e: December 7 , 2015 MEMORANDUM

SUBJECT: Registration Review: Preliminary Problem Formulation for Environmental Fate, Ecological Risk, Endangered Species, and Human Health Drinking Water Exposure Assessments for Prothioconazole

TO: Brian Kettl , Chemical Review Manager Tom Myers, Team Leader Risk Management and Implementation Branc h 2 Pesticide Re

- Evaluation Division (7508P)

FROM: Mary Clock

- Rust, Biologist Cheryl Sutton, Ph.D., Environmental Scientist Environmental Risk Branch IV Environmental Fate and Effects Division (7507P)

REVIEWED BY: Catherine Aubee, Senior Effects Scientist James N. Carleton, Ph.D., Senior Fate Scientist Katrina White, Ph.D., Risk Assessment Process Leader Environmental Risk Branch IV Environmental Fate and Effects Division (7507P)

THROUGH: Jean Hol mes, D.V.M., M.P.H., Branch Chief Environmental Risk Branch IV Environmental Fate and Effects Division (7507P)

### 2 

# 1. Executive S ummary

The Environmental Fate and Effects Division (EFED) has completed the preliminary problem formulation (attached) for the ecological risk, environmental fate, endangered species, and drinking water assessments to be conducted as part of the R egistration R evi ew of prothioconazole (2

- (2

- (1

- chlorocylocpropyl)

- 3

- (2

- chlorophenyl)

- 2

- hydroxy

- propyl)

- 2,4

- dihydro(1,2,4)

- triazol

- 3

- thion ; PC Code 113961 ; CAS No. 178928

- 70

- 6 ). The problem formulation describes the methods planned to be used during the completion of drin king water and ecological risk assessments in support of R egistration R eview and provides an overview of the environmental fate, ecological effects, and potential risks associated with the use of prothioconazole as well as uncertainties unique to risk asse ssment of prothioconazole. This document also identifies additional studies that would be beneficial to the conduct of an ecological risk assessment. Major findings include:

• The environmental fate databas e is relatively complete, with some exceptions. In all of the metabolism studies, it is uncertain whether or not greater amounts of soil

- bound material could have been extracted using harsher or more appropriate methods. For the parent compound, a n aerobic soil metabolism study is needed on an additional soil, and an anaerobic aquatic study is need on an additional sediment/water system. For each of the studies, it is important that the extraction is more rigorous than that which was used in previously submitted studies, and that the natu re of the unextracted residues be clarified to the extent possible. Guidance is available at http://www2.epa.gov/pestici de

- science

and

- assessing

- pesticide

- risks/guidance

- addressing

- unextracted

- pesticide

- residues

.

• In the event that new, useful information is not received on unextracted residues, which may be applied to the understanding of previously submitted studies as wel l, unextracted residues will continue to be considered as parent compound and continue to be treated as such in exposure modeling.

• More information is needed to address uncertainties in the ecological effects database for prothioconazole and its degradate s. T here are signi ficant toxicity data gaps f or the parent compound as well as the major prothioconazole degradates (prothioconazole

- desthio, prothioconazole

- S

- methyl )

. Ecological effects data needs : Prothioconazole Parent Compound

o Non

- guideline: Chron ic toxicity to benthic invertebrates (whole sediment; 3 test species: freshwater amphipod, freshwater midge, and estuarine/marine amphipod) (TGAI)

 EFED recommends that the registrant consider Agency

- wide guidelines for chronic testing of freshwater and estuarine/marine organisms, because the 850 guidelines are in the process of being finalized. A protocol must be submitted for review prior to initiating the studies.

o OCSPP 850.2100: Acute Oral Toxicity with passerine species (TGAI)

o OECD TG 237 and Non

- gu ideline special studies: Honeybee larval acute and chronic oral toxicity studies (TGAI)

o Non

- Guideline: Honey bee adult chronic oral toxicity test (TGAI)

### 3 o Special study OECD TG 75 and OSCPP 850.3040: Semi

- field testing for pollinators (Tier II) and Field tes ting for pollinators (Tier III) (both studies that are conditionally required based on the results of the Tier I

– laboratory based studies listed above; if needed these additional field studies will be discussed pending the results of the acute and chroni c adult and larval oral toxicity studies to honey bees and/or Tier II studies (for the full field study); (TEP).

Prothioconazole

- Desthio

o OCSPP 850.1010: Acute toxicity for freshwater invertebrates

o OCSPP 850.1075:Acute toxicity for estuarine/marine fish

o OCSPP 850.1400 Early life stage toxicity test with freshwater fish

o OCSPP 850.4500 Algal Toxicity with Non

- v ascular estuarine/marine diatom

o OCSPP 850.2100: Acute Oral Toxicity with avian passerine species

Prothioconazole

- S

- methyl

o OCSPP 850.1025, 850.1035 , 850.1045, 850.1055: Acute toxicity to estuarine/marine invertebrates

Uncertainties T he fate data base for prothioconazole indicate s that it degrades into other compounds (prothioconazole

- desthio, prothioconazole

- S

- methyl and 1,2,4

- triazole, among other degradates)

. For each of the degradates, t here are significant uncertainties associated with the toxicity to non

target organisms. Those data that are the most critical for a complete and robust risk assessment have been identified in this document

. Where possible, EFED will make use of limited data to inform the risk assessment. For example, c hronic data for estuarine/marine fish conducted with
p rothioconazole

- d esthio were n ot submitted by the registrant. However, measurement endpoints can be estimated ba sed on an acute

- to

- chronic ratio (ACR) for freshwater fish if a chronic freshwater fish toxicity study ( 850.1400) is submitted for the most sensitive species tested in the acute toxicity study (850.1075; Rainbow trout, Oncorhynchus mykiss ).



# 2. Introduction

Prothioconazole is a broad

- spectrum, systemic fungicide belonging to the conazole (triazolinthione) class of fungicides. This class of compounds is characterized structurally by inclusion of a nitrogen

- containing five member ring (azole). Prothioconazole is currently the sole fungicide in triazolinthiones, which was added in 2012 to the Group 3 of DMI ( DeMethylation Inhibitor) fungicides classified by the Fungicide Resistance Action Committee. Conazole fungicides act through disruption of normal fungal cell membrane structure and function primarily through interactions or inhibitions of ergosterol synthesis, the predominant membrane sterol component. Prothioconazole’s specific mode of action is through the inhibition of demethylation of two precursors o f sterols in fungi (lanosterol and 24

- methylene dihydrolano

sterol).

Prothioconazole is app lied via ground or aerial spray, prior to and during specified growth phases of the target crops. It is also used as a seed treatment on multiple crops

. More
comp lete information on applications of prothioconazole is provided in the Biochemical Profile

### 4 (BCP) that was developed for prothioconazole by the Biologic and Economic Analysis Division (BEAD ; USEPA

, 2015 b ).

EFED evaluated the most recent ecological risk ass essments for prothioconazole in association with the updated toxicity, exposure, and usage information to determine if sufficient data are available and if further updates are needed to support R egistration R eview. Recent risk assessments include a 2012 a ssessment for the new use of prothioconazole on seeds of cereal grains crop groups 15 & 16 (except sorghum and r ice ), as a seed treatment on corn (field, sweet, pop), and as a foliar treatment on soybean at an increased rate ( USEPA 2012 b

. ); and a 2012 new

use assessment on bushberry (crop subgroup 13

- 07b), low growing berry subgroup, except strawberry (crop subgroup 13

- 07h) and cucurbit vegetables (crop group 9; U SEPA, 2012 c )



### . In addition, EFED considered the latest Agency science policies and risk ass essment methodologies. The structure of prothioconazole , as well as the chemical names and other identifiers can be found in Table 3

. 

# 3. Use Characterization

Prothioconazole is registered for use on a variety of crops, with the ma jority of use (total pounds applied to crops) on wheat, corn, sugar beets, peanuts, dry beans/peas, soybeans and barley (USEPA 2015 a )

. Prothioconazole is also registered for use on alfalfa, beans, bushberries, rice, small grains, crambe, cucurbits, mustard, potatoes, small fruit

, cranberries, and nursery stock . It is registered for use as a seed treatment on multiple crops , including cereal grains and potatoes (USEPA, 2015 b ) . It is not registered for use on any non

- agricultural sites.

Based on the BEAD Chemical P rofile (BCP) produced by BEAD (USEPA 2015 b ; located in the docket), prothioconazole has been used to control or suppress some important crop diseases such as anthracnose leaf blight on corn, Ascochyta blight on dry beans/peas, white mold on peanuts, frog e ye leaf spot on soybeans, Rhizoctonia solani on sugar beets, and Fusarium head blight (scab) on wheat. Prothioconazole is registered for use on nursery stock

, such as nursery seedlings of loblolly pine

, to control pitch canker and other diseases. The agr icultural use of prothioconazole in the United States has been increasing since its registration in 2007, treating a total of approximately 11,000,000 acres in 2013 for all crops combined (USEPA 2015 b )

. Prothioconazole is formulated as a liquid soluble concentrate, emulsifiable concentrate, and flowable concentrate

. There are multiple pesticide products containing prothioconazole and other active ingredients, such as Stratego 731® and Stratego YLD® (containing 10% prothioconazole and 32.3% trifloxystrobi n, PC code 129112) and Evergol Energy® [containing 7.18% prothioconazole, 3.59% penflufen (PC code: 100249) and 5.74% metalaxyl (PC code 113501)]. Prothioconazole is applied using broadcast, banded, chemigation, and seed treatment methods. EFED will use a pplication scenarios that result in maximum exposure scenarios for a given use for the risk assessment

. 

# 4. Conclusions from Previous Risk Assessments

The Agency has conducted multiple environmental fate and ecological risk assessments on prothioconazole that serve as a basis for this scoping document, including the initial new

### 5 chemical risk assessment in 2006 and several subsequent new use assessments over the past 8
years (USEPA 2006d

, - 2008,

- 2010 b

, - 2012 b )

.



## a. **Ecological Risk Assessment**

The results of previous screening

- level risk assessments indicate that the uses of prothioconazole have the potential for direct adverse effects to Federally

- listed threatened or endangered species (hereafter referred to as “listed”) and non

- listed organisms. Based on previous c onservative screening level assessment s, level

- of

- concern (LOC) exceedances were calculated for registered uses of prothioconazole. The registered uses were determined to have the potential for dire ct adverse effects to listed freshwater fish and aquatic

- phase amphibians, freshwater invertebrates

, estuarine/marine invertebrates, mammals, listed and non

- listed vascular and non

- vascular aquatic plants and listed semi

- aquatic dicot plants. Also, as sho wn in previous risk assessments, registered uses of prothioconazole have the potential for direct adverse effects to aquatic and terrestrial plants and mammals (on a chronic exposure basis).

The major ecological risk and exposure conclusions from previous assessments are summarized in Table 1

. Table 1. Major Risk and Exposure Conclusions from Previous Prothioconazole Risk Assessments

Birds Mammals Terr. Plants Terr. Inverts Fish BCF Aquatic Inverts Aquatic Plants Groundwater Contamination Persistence Degrad at es of Concern



### -- √ √ NA 

### √



### -- √ √ √ √ √ √ = at least one LOC has been exceeded in previous assessments; NA = RQs have not been calculated previously.



## b. **Drinking Water Exposure Assessments**

Prothioconazole degrades relatively quickly in the environment ( decreased to 7.9

- 52.1 % of the applied by 1 day in aerobic soil) ; however, its degradates, primarily prothioconazole

desthio and prothioconazole

- S

- methyl, are more persistent than the parent. As documented in previous prothioconazole asse ssments, a total toxic residues approach has been used for drinking water exposure modeling. Combined residues of concern include the parent and the two degradates stated above

, plus unextracted residues which could not be ruled out as consisting of
paren t compound based on the minimal extraction techniques used

. The 1,2,4

- triazole degradate

, which has different toxicity endpoint s from prothioconazole with respect to human health, was characterized in a separate, cumulative triazole assessment and was, th erefore, not considered separately in previous drinking water assessments (DWA).

A drinking water exposure assessment for the proposed new uses on Crop Subgroup 13

- 07B (bushberry) and Crop Group 9 (cuc ur bit vegetables) was conducted for proth ioconazole in 2012 (USEPA, 2012 c ). The maximum application rates for bushberry and cucurbit vegetables were not higher than the application rates assessed in previous DWAs (USEPA 2010; USEPA 2012 a ). Because those new uses would result in lower EDWCs than in the pr evious DWAs, the new uses were not modeled separately to determine surface water EDWCs. Instead, previously determined estimated drinking water exposure (EDWC) values were cited, although new values

### 6 were determined based on changes in the percentage crop area (PCA) factor that were implemented since the former assessment was completed. The surface water acute (1

- in

- 10

- year peak) EDWC, based on corn use, increased slightly relative to the previous assessment, from 94.7 to 99.0 μg/L . The chronic (1

- in

- 10

- year annual mean) and cancer (30

- year mean) EDWCs, based on the cranberry use, increased to 91.9 μg/L from previous values of 84.3 μg/L (chronic, based on corn use) and 76.2 μg/L (cancer, based on rice use). The acute and chronic EDWCs ( both 0.83 μg/L ) provided for groundwater sources of drinking water were not updated from the most recent DWA. Groundwater EDWCs were based on use on nursery seedlings and were determined using the SCI

- GROW model

. EDWCs for the prothioconazole degradate 1,2,4

- triazole, were calculated in support of the 2006 aggregate assessment for triazole

- derivative fungicides, including fenbuconazole (USEPA, 2006 a , 2006 b ). The highest 1,2,4

- triazole EDWCs calculated were for the turf use, which resulted in the surface water EDWCs (using PRZM

- EXAMS) of 0.041 mg/L (acute), 0.011 mg/L (chronic) and 0.0027 mg/L (cancer). A groundwater EDWC of 0.001 mg/L was calculated for 1,2,4

- triazole using SCI

- GROW. The 1,2,4

- triazole application rate used to determine EDWCs was based on a t urf use and was obtained from molecular weight conversion times myclobutanil application rate times max percent formation rate for triadimefon (turf = (69.0/288.78)*1.73*0.307), as this was believed to be the maximum percent formation rate for all fungicid es in the conazole class.



## c. **Clean Water Act Programs**

Prothioconazole is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act ( http://water.epa.gov/lawsregs/lawsguidance/cwa/tmdl/intro.cfm ). No Total Maximum Daily Load (TMDL) criteria have been developed for prothioconazole

. Aquatic benchmarks have not been established for prothioconazole ( http://www2.epa.gov/pesticide

- science

- and

- assessing

pesticide

- risks/aquatic

- life

- benchmarks

- pesticide

- registration ) . Any data submitted or otherwise located as part of the R egistration R eview process may be used to update aquatic life benchmarks if applicable.



# 5. Environmental Fate and Transport

Prothioconazole [ 2

- [2

- (1

- Chlorocyclopropyl)

- 3

- (2

- chlorophenyl)

- 2

- hydroxypropyl]

- 1,2

- dihydro

- 3H

- 1,2,4

- triazole

- 3

- thione ; CAS No. 178928

- 70

- 6 ; PC code 11396 1] dissipates in the environment by aqueous photolysis and microbial degradation in soil

. Prothioconazole is stable to hydrolysis . Prothioconazole photolyzes in shallow, clear surf ace waters (half

- life of 9 .7 days)

, but does not photolyze on soil. In water, it degrades to prothioconazole

- desthio, which appears to resist further photolytic degradation ( residues of concern t 1/2 

### = 101 d). In soil,
p rothioconazole degrades relatively quickly to two major persistent degradates which are assumed to be of similar toxicity to that of the parent (based on structural similarity), prothioconazole

- desthio and prothioconazole

- S

- methyl. Prothioconazole and its degradates are not expected to volatilize appreciably (vapor pressure 3 x 10

- 9 

### torr ). Parent p rothioconazole

### 7 rapidly degrade s in aerobic soil ( in submitted data, decreased to 7.9

- 52.1 % of the applied by 1 day and was <2.0

- 23.2 % of the applied by 7 days ). However, b ased on available data, prothioconazole together with its major degradates do not appear to undergo significant microbial degradation in soil (t 1/2 

### = 462

– 1386 d) or in water (t 1/2 

### = 67

– 433 d) , so may potentially accumulate in soil or in t he sediment of aquatic environments with repeated application . The mobility of parent prothioconazole ha s not been successfully characterized due to rapid degradation that occurred during mobility studies

. However

, the major degradate that formed in the largest amounts (prothioconazole

- desthio) is moderately mobile based on its organic carbon partition coefficient (K oc 

### = 523

– 625 mL/g oc 

### ) and the F ood and A griculture O rganization soil mobility classification scheme (FAO, 2000) . The other major degradate, prothioconazole

- S

- methyl, which is formed in smaller relative amounts, is slightly mobile (K oc 

### = 1973

– 2993 mL/g oc 

### ). These two major degradates were considered to be of similar or greater toxicity compared with the parent and were included in previous a quatic exposure estimates ( see USEPA 2006 d ). There is potential for the degradates prothioconazole

- desthio and prothioconazole

- S

- methyl to leach to groundwater in vulnerable aquifers, such as those underlying coarse

- textured soils low in organic matter. Prothioconazole and prothioconazole

desthio do not appear to bioconcentrate in fish and are not expected to bioaccumulate in aquatic ecosystems, although a BCF cannot be calculated due to lack of a clear accumulation plateau.

T errestrial field data show that prothioconazole parent dissipates from the top layer of soil quickly (with a DT 50 

### of less than 2 or 3 days), but that prothioconazole

- desthio dissipates from the top layer of soil much more slowly (DT 50 

### of 85

- 315 days). Prothioconazole was not detec ted below 15 cm in any of the three tested fields in California, Georgia or New York. Prothioconazole

- desthio was detected at levels above the LOQ down to 30 cm and at levels above the minimum detection limit [MDL] but below the LOQ down to 45 cm in one r eplicate in the California field study, and at levels below the LOQ at one to two sampling times in the Georgia and New York field studies. Prothioconazole

- S

- methyl was detected below 15 cm only in a single replicate (below LOQ) in the field study in Cali fornia.

Persistence was observed in aquatic field dissipation studies, with long half

- lives for both prothioconazole and prothioconazole

- desthio in sediment (DT 50 

### of 90

- 204 days). Dissipation half

- lives in paddy water were extremely short (0.6

- 1.7 days), likely more due to adsorption than degradation given the compound’s slow rate of biotic degradation in lab studies and its photolysis half

- life of almost 10 days in clear shallow water

. Prothioconazole was detected at only three sampling intervals at concentrations below the LOQ but above the MDL in sediment below 3 inches. Prothioconazole

- desthio was detected at 3

- 6 inch deep sediment through 28 days after treat ment (D AT ) in the Arkansas flooded field and through 60 DAT in the Arkansas flooded and cropped field. Prothioconazole

- S

- methyl was detected below 3 inches in sediment only

, at three sampling intervals in the Arkansas flooded and cropped field.

A selection of environmental fate and transport properties of prothioconazole is summarized Table 2

.

### 8 Table 2

. Chemical Properties and Environmental Fate Parameters of Prothioconazole.

Parameter Value Description/Comments Source Selected Physical/Chemical Parameters

Molecular mass (molecular formula) 344.26 g/mol

− MRID 46246003

Vapor pressure (20°C) 3 x 10

- 9 Torr Limited volatilization. MRID 46246003

Aqueous solubility (20 ° C) pH 4: 5 mg/L or ppm pH 8: 300 mg/L or ppm pH 9: 2000 mg/L Readily soluble. Solubility increases with increases in pH. MRID 46246003

Henry’s Law Constant (20°C) 2.96 x 10

- 10 atm

- m 3 /mol Not expected to volatilize from water or wet surfaces MRID 46246003

Log octanol

- to

- water partition coefficient

( log K OW ; 20 o C ) Unbuffered: 4.05 pH 4: 4.16 pH7: 3.82 pH9: 2.00 Potential for bioaccumulation at neutral and acidic pH. MRID 46246003

Acid dissociation constant ( pKa; 20 o C) 6.9 (parent compound) Weak acid, anion at neutral and alkaline pHs. MRID 46246003

Persistence

Hydrolysis half

- life (50 ° C, 25 ° C) Parent prothioconazole Stable at pH 4,7,9

Prothioconazole

- desthio Stable at pH 4,7,9 Do not hydrolyze. MRID’s 46246505, 46246506

Aqueous photolysis half

- life (pH 7; 25 ° C) Prothioconazole: 9.7 days

Prothioconazole

- desthio: Increasing at study termination

Prothioconazole and Prothioconazole

desthio: 101.9 days

(Prothioconazole

- S

- methyl is not formed from prothioconazole via aqueous photolysis.) Value corrected to represent natural sunlight at 40°N latitude; uncorrected laboratory half

- life of 19.9 days for both phenyl and triazole labels (continuous irradiation; xenon lamp). MRID 46246507

Soil photolysis half

- life (25 ° C) Prothioconazole and Prothioconazole

desthio: s table

(Prothioconazole

- S

- methyl is not formed

from prothioconazole soil photolysis.) Half

- life could not be calculated as parent degraded faster in dark samples than in irradiated

samples. Phenyl label only. Concentration of prothioconazole

- desthio

was still increasing at

study termination. MRID 46246510

### 9 Parameter Value Description/Comments Source

Aerobic soil metabolism half

- life (24°C) Prothioconazole total residues of concern: 533 day s (silt; phenyl), 866 days (silt; triazole) 990 days (loamy sand; phenyl), 1386 days (loamy sand; triazole) 866 days (sandy loam; phenyl) 462 days (silty clay loam; phenyl) Half

- lives are based on combined data for parent prothioconazole, prothioconazole

- desthio, and prothioconazole

- S

methyl per sampling interval. Unextracted residues were added in as residues of concern

. Analytical method may have been inadequate based on h igh levels of unextracted residues. Additional data obtained

using more exhaustive extractions would be useful

. MRID’s 46246511
46246512

Aerobic aquatic metabolism half

- life (25 ° C) Prothioconazole total residues of concern: 433.2 days (H, total system, phenyl), 346.6 days (H, total system, triazole) 106.6 days (A, total system, phenyl), 67.3 days (A, total system, triazole)

17.2 days (H, water layer, phenyl), 16.2 days (H, water layer, triazole)
23.3 days (A, water layer, phenyl), 21.7 days (A, water layer, triazole) Two systems studied: (H) Honniger Weiher pond (loam/water) and (A) Anglerweiher lake (loamy sand/water). Half

- lives are based on combined data for parent prothioconazole,

prothioconazole

- desthio, and prothioconazole

- S

methyl per sampling interval. Unextracted residues were added in as residues of concern

. MRID 4624 6515

Anaerobic aquatic metabolism half

- life (25 ° C) Prothioconazole total residues of concern: stable (total system); 56.8 days (water layer) Single sediment/water system (Fuquay, GA pond) studied. Sandy clay loam/water, phenyl label only. Additional data are

required for a second sediment/water system

, with use of more exhaustive extractions

. Half

- lives are based on combined data for parent prothioconazole, prothioconazole

- desthio, and prothioconazole

- S

methyl per sampling interval. Unextracted residues were added in as residues of concern. MRID 46246516

Mobility

### 10 Parameter Value Description/Comments Source

Organic carbon

normalized Freundlich

coefficients (K FOC ) (mL/g OC ) LS SCL SL S

Prothioconazole --

-- -- -- Parent mobility cannot be determined due to

instability and low column resolution. Very high sorption estimated,

lower mobility than transformation products MRID’s 46246539
46246504

Prothioconazole

- desthio 523 536 617 625 U sed four soils: loamy sand (LS, 0.79% OC); silty clay loam (SCL, 1.66% OC); sandy loam (SL, 2.02% OC); silt (S,

2.14% OC). Follows Koc model. MRID 46246450

Prothioconazole

- S

- methyl 1973 2484 2772 2995 Used same soils as MRID 46246450. Follows Koc model. MRID 46246501

Freundlich soil

- water partition coefficients (K F ) (mL/g) LS SCL SL S

Prothioconazole

-- -- -- -- Same as for K OC
. MRID’s 46246539 46246504

Prothioconazole

- desthio 4.13 8.90 12.4 6 13.3 8 Same as for K OC
. MRID 46246450

Prothioconazole

- S

- methyl 15.6 41.2 56.0 64.1 Same as for K OC
. MRID 46246501

Field Dissipation

Terrestrial field dissipation (half

- life in surface soil ; leaching depth) California (sandy loam/loam): Prothioconazole: 2.2 days; Not detected above LOD below a depth of 15 cm nor after 7 DAT.

Prothioconazole

- desthio: 84.5 days; Detected above LOD to a depth of 45 cm and through 307 DAT. For degradate h alf

- lives, the day of maximum concentration of the degradate wa s used as day

zero in the regression. 46246517

### 11 Parameter Value Description/Comments Source Georgia (sand/sandy loam): Prothioconazole: 4.7 days; Not detected above detection limit (LOD) below a depth of 15 cm nor after 14 days after treatment ( DAT )

.

Prothioconazole

- desthio: 96.3 days; Detected above LOD to a depth of 30 cm through 7 DAT. For degradate h alf

- lives, the day of maximum concentration of the d egradate wa s used as day

zero in the regression. 46246518

New York (loamy sand): Prothioconazole: 96.3 days; Not detected above LOD below a depth of 15 cm nor after 211 DAT.

Prothioconazole

- desthio: 315.1 days; Not detected above LOD below a depth of 15 cm (except for one sampling interval (211 DAT) where detect ed above LOD to 30 cm); detected above LOD through study completion (567 DAT). For degradate h alf

- lives, the day of maximum concentration of the degradate wa s used as day

zero in the regression. 46246519

Aquatic field dissipation (half

- life) California (clay): Prothioconazole: 203.9 days (in sediment) ; 1.7 days (in paddy water)
Prothioconazole

- desthio:

122 days (in sediment) For degradate h alf

- lives, the day of maximum concentration of the degradate wa s used as day

zero in the regression. 46246522

Arkansas (loam): Prothioconazole: too few detections in sediment ; 4.8 days (in paddy water)

Prothioconazole

- desthio: 121.6 days (in sediment) For degradate h alf

- lives, the day of maximum concentration of the degradate wa s used as day

zero in the regression. 46246523

Arkansas

- cropped (loam): Prothioconazole: too few detections in sediment ; 0.6 days (in paddy water)

Prothioconazole

- desthio: 90.0 days (in sediment) For degradate h alf

- lives, the day of maximum concentration of the degradate wa s used as day

zero in the regression. 46246524

Fish Bioconcentration

### 12 Parameter Value Description/Comments Source

Fish bioconcentration factors (steady

- state); depuration rate Prothioconazole and prothioconazole

desthio do not appear to bioaccumulate. BCF c ould not be calculated due to lack of a clear accumulation plateau. 46246034
46246035



### Unextracted residues were observed at maximums of 38.2

- 56.4% of the applied radioactivity across both soils and both labels by the end (365 d) of an aerobic soil metabolism study (MRID 46246511) in which samples were only extracted once with acetonitrile/w ater. Unextracted residues were also high in other studies, at 46.7% of the applied in an aerobic aquatic metabolism study (MRID 46246515, triazole label, 121DAT) and 26.5% in an anaerobic aquatic metabolism study (MRID 46246516, phenyl label, 360DAT). R esidue extraction was attempted by extracting with a relatively mild acetonitrile/water solution (80:20, v:v for aerobic soil metabolism, 90:10, v:v for aerobic aquatic metabolism, 80:20 or 70:30, v:v for anaerobic aquatic metabolism) on a mechanical shake r followed by hot extraction by reflux for all studies involving soil. Additionally, some aerobic aquatic metabolism study sediment samples were extracted further with acetone/concentrated HCl (99:1, v:v). It is uncertain whether or not greater amounts o f soil

- bound material could have been extracted using more appropriate methods (see guidance at http://www2.epa.gov/pesti cide

- science

- and

- assessing

- pesticide

risks/guidance

- addressing

- unextracted

- pesticide

- residues )

. Because high levels of unextracted material in laboratory metabolism studies precluded accurate determinations of the biotic degradation rates for parent proth ioconazole, a total toxic residues (TTR) method, including unextracted material, was utilized in past assessments for environmental exposure modeling. Additional details on this, and on the environmental fate and transport of prothioconazole and its degradates can be found in the June 1, 2006 Ecological Risk Assessment (USEPA, 2006 d ). Because of this uncertainty associated with soil extraction, unextracted residues will be included in the ecological risk assessment for Registration Review unless new data clearly indicate that the unextracted residues are not the parent compound or can be considered bound residues under current policy ( USEPA 20 14 b )

.



## a. **Transformation Products**

The major organic degradates of prothioconazole in submitted environmental f ate studies

were prothioconazole

- desthio (SXX0665), prothioconazole

- S

- methyl (WAK7861

- S

- methyl), prothioconazole

- thiazocine (JAU6476

- thiazocine), and 1,2,4

- triazole

. Prothioconazole

- desthio is formed quickly and in large amounts (up to 56% of applied) fro m all degradation processes evaluated. It is the result of desulfonation of prothioconazole parent. Prothioconazole

- S

- methyl is also formed in large amounts from anaerobic aquatic metabolism (78% of applied) , and in lesser amounts from aerobic soil metab olism and aerobic aquatic metabolism. It is the result of methylation of the sulfur of prothioconazole parent. Both of these identified major transformation products are expected to form in large relative proportions in both terrestrial and aquatic envir onment compartments. Based on submitted toxicity studies, prothioconazole

desthio and prothioconazole

- S

- methyl are expected to exhibit similar toxicity to parent prothioconazole. Therefore, since these degradates are expected to form in high relative amo unts and are considered toxic, both prothioconazole

- desthio and prothioconazole

- S

- methyl will be considered in the drinking water and ecological risk assessment s as part of a total toxic residue

### 13 approach

. The degradate 1,2,4

- triazole was a major degradate only in the aqueous photolysis (11.9%) and aerobic aquatic metabolism studies (maximum of 41.8%) ; in aerobic soil metabolism studies, it was only detected at <2% of the applied

. Although it was not moni tored in some studies which utilized only a phenyl radiolabel, the parent compound was essentially stable or showed minimal degradation in those studies. Based on submitted toxicity data for 1,2,4

- triazole, this degradate appears to be less toxic than the parent compound to all taxa with the exception of birds. Table summarizes the major transformation products of prothioconazole and their maximum amount s formed.

Prothioconazole

- thiazocine is formed at a maximum of 14.1% of applied radioactivity from aqueous photolysis only. This mode of degradation is only likely to be influential in clear, shallow water, under clear atmospheric conditions. In actual environmental systems, aqueous photolysis is likely to proceed at a much slower rate and the degradate is likely to form only in small amounts under very specific circumstances in the environment. Thus, the Health Effects Division (HED) has very low conc ern regarding the hazard associated with this compound, and prothioconazole

- thiazocine will not be considered in the drinking water assessment (USEPA, 2006 c )

. A variety of minor degradates were also observed in the soil photolysis and/or in the soil and aquatic metabolism studies. The identified minor transformation products of prothioconazole include: prothioconazole

- sulfonic acid (JAU6726), prothioconazole

- triazolinone (WAK7860), prothioconazole

- 3, 4, 5, and 6

- hydroxy

- desthio (3, 4, 5, and 6

- HO

- SXX066 5), 2

- chlorobenzoic acid, and JAU6476

- triazolylketone (WAK4995). Additional information on both the major and minor transformation products may be found in USEPA, 2006 d

.

### 14 Table 3

. Prothioconazole and Its Major Environmental Degradates

. Code Name/ Synonym Chemical Name Chemical Structure Study Type Ref. (MRID) Maximum %AR (day) A 

### Final %AR (study length)

PARENT

Prothioconazole 2

- (2

- (1

- chlorocylocpropyl)

- 3

- (2

- chlorophenyl)

- 2

- hydroxy

- propyl)

- 2,4

- dihydro(1,2,4)

- triazol

- 3

- thion CAS No.: 178928

- 70

- 6 SMILES Code: C1C1(C(Cc2ccccc2C1)( CN2N=CNC2=S)O)CC 1 MW: 344.26 g/mol MAJOR TRANSFORMATION PRODUCTS

Prothioconazole

- desthio: 2

- [2

- (1

- Chlorocyclopropyl)

- 3

- (2

- chlorophenyl)

- 2

- hydroxy

- propyl]

- 1,2

- dihydro

- 3H

- 1,2,4

- triazole
MW: 312.2 g/mol Hydrolysis 46246505 5. 2 % (168 hr ) 5.2% (168 hr)

Aq photolysis 46246507 54.8 % ( 11 d ; phenyl label )

55.7% (11 d; triazole label) 54.8% (1 8 d)

53.2% (18 d)

Soil photolysis 46246510 38.5 % ( 7 d) ( 25 .4% at 7 days in dark control) 38.1% (15 d) (29.4% at 15 days in dark

control)

### 15 Code Name/ Synonym Chemical Name Chemical Structure Study Type Ref. (MRID) Maximum %AR (day) A 

### Final %AR (study length)

Aerobic soil (parent applied) 46246511, 46246512 46.5

- 49.4 % ( 7 d ; both labels )

38.4

- 41.2% (90 d; both labels)

41.3% (3 d)

20.9% (7 d) 6.1

- 6.3 % ( 365 d)

21.9

- 23.7%

(365 d)

42.3% (120 d)

18.5% (120 d)

Aerobic soil (desthio applied) 46246513 80

- 89% (0 d) 2.3

- 19.6% (120 d)

Aerobic aquatic 46246515 26.9% (14 d; in sediment, both labels)

32.3% (7 d; in water, phenyl label) 54.6% (7 d; in total system, phenyl label) nd

– 1.2% (121 d; water , both labels )

7.1

- 11.1 % ( 121

d ; sediment, both labels )

8.2

- 11.1% (121 d; total system,

both labels)

Anaerobic

aquatic 46246516 Not determined;

- desthio formation determined to be artifact of storage and, therefore, added to parent (parent+desthio at 95.2% in total system at 0 days) 1.4 % ( 360 d)

### 16 Code Name/ Synonym Chemical Name Chemical Structure Study Type Ref. (MRID) Maximum %AR (day) A 

### Final %AR (study length)

TFD (CA) 46246517 191.0 ug/kg soil (3 d, 0

- 15 cm) 2.2 ug/kg soil (553 d)

TFD (GA) 46246518 82.0 ug/kg soil ( 0 d, 0

- 15cm) ND

- 3.0 ug/kg soil ( 421

- 5 32 d)
TFD (NY) 46246519 221.0 ug/kg soil ( 5 8 d, 0

- 15cm) 82.5 ug/kg soil (5 67 d)

AFD 46246522, 46246523, 46246524 CA: 32.7 ug/kg sediment (14 d,

0

- 3 in); 50.3 ug/L paddy water (3 d)

AK: 63.2 ug/kg sediment ( 3 d, 0

- 3 in) ; 109.8

ug/L paddy water ( 0 d) CA: 20.4 ug/kg sediment (364 d, 0

- 3 in); 0.69

ug/L paddy water (60 d)
AK: 4 .4 ug/kg sediment ( 365 d, 0

- 3 in); 0. 8

ug/L paddy water (60 d)

Prothioconazole

- S

- methyl: alpha

- 1(1

- chlorocyclopropyl)

- alpha

- [(2

- chlorophenyl)methyl]

- 3

- (methylthio)

- 1H

- 1,2,4

- triazole

- 1

- ethanol MW: 358.3 g/mol Aerobic soil (parent applied) 46246511, 46246512 11.3

- 12.8 % ( 1 d ; both labels )

13.7

- 14.6% (7 d; both labels)

3.8

- 5.5% (1

- 7 d) 2.8

- 3.1 % ( 365 d)

7.1

- 7.6% (365 d)

1.5

- 1.7% (7d)

Aerobic soil (S

methyl applied) 46246514 77

- 80% (0 d) 2.4

- 17.2% (125 d)

Aerobic aquatic 46246515 9.6% (7 d; in sediment, triazole label) nd ( 121 d ; water, both

labels )

### 17 Code Name/ Synonym Chemical Name Chemical Structure Study Type Ref. (MRID) Maximum %AR (day) A 

### Final %AR (study length) 3.1% (7 d; in water, triazole label) 12.7% (7 d; in total system, triazole label) 1.9

- 3.1% (121 d; sediment

and total system, both labels)

Anaerobic

aquatic 46246516 78.2% (240 d; in sediment) 9.9% (30 d; in water) 78.2% (240 d; in

total system) <0.2% (360 d; water) 76.1 % ( 360 d ; sediment and total system )

TFD (CA) 46246517 14.2 ug/kg soil (3 d, 0

- 15 cm) 1.9 ug/kg soil (63 d)

TFD (GA) 46246518 10.1 ug/kg soil (7 d, 0

- 15cm) ND

- 1.3 ug/kg soil ( 120

- 141 d)

TFD (NY) 46246519 46.9 ug/kg soil ( 7 d, 0

- 15cm) 4.0 ug/kg soil ( 567 d)

AFD (CA) 46246522, 46246523, 46246524 CA: 10.0 ug/kg sediment ( 122 d,

0

- 3 in); 0.23 ug/L paddy water (3 d)
AK: 16.7 ug/kg sediment ( 14 d, 0

- 3 in); 3.0 ug/L paddy water ( 1 d) CA: 5.3 ug/kg sediment ( 364 d, 0

- 3 in); 0.02

ug/L paddy water ( 28 d)

AK: ND sediment ( 365 d, 0

- 3 in); 0.1

ug/L paddy water (7

- 14 d)

### 18 Code Name/ Synonym Chemical Name Chemical Structure Study Type Ref. (MRID) Maximum %AR (day) A 

### Final %AR (study length)

1,2,4

- triazole Aq photolysis 46246507 11.9% (18 d; triazole label) 11.9% (18 d )

Aerobic soil 46246511, 46246512 <2.0% (120, 272, & 365 d; (triazole label) nd

- <2 % ( 365 d)

Aerobic aquatic 46246515 6.1% (121 d; in sediment, triazole label) 37.2% (121 d; in

water, triazole label) 41.8% (121 d; in

total system, triazole label) 6.1% (121 d; in sediment, triazole label; one system) 37.2% (121 d; in water, triazole label; one system) 41.8% (121 d; in total system, triazole label)

TFD (CA) 46246517 7.3 ug/kg soil (29 d, 0

- 15 cm) 1.3 ug/kg soil (553 d , 30

- 45

cm )

TFD (GA) 46246518 4.9 ug/kg soil ( 120 d, 0

- 15cm) ND

- 4.5 ug/kg soil (532 d; 15

- 30 cm)

TFD (NY) 46246519 3. 3 ug/kg soil (422 d, 0

- 15cm) ND

- 3.1 ug/kg soil ( 567 d ; 0

- 15 cm )

AFD (CA) 46246522, 46246523, 46246524 CA: 3.3 ug/kg sediment ( 273

- 364 d, 0

- 3 in); CA: 3.3 ug/kg sediment (364 d, 0

- 3 in); 0.3 

# N H

N N

### 19 Code Name/ Synonym Chemical Name Chemical Structure Study Type Ref. (MRID) Maximum %AR (day) A 

### Final %AR (study length) 0.13 ug/L paddy water (7 d)
AK: 2.9 ug/kg sediment ( 270 d, 0

- 3 in); 0. 5 ug/L paddy water ( 1 d) ug/L paddy water (3 d)

AK: 2.9 ug/kg sediment ( 365 d, 0

- 3 in); 0.3

ug/L paddy water (3 d)

Prothioconazole

thiazocine Aq photolysis 46246507 14.1% (5 d; phenyl label)

9.5% (11 d; triazole label) 8.4% (18 d)

9.1% (18 d)

Studies conducted with both phenyl and triazole radiolabels include: aerobic soil metabolism (MRID: 46246511 only), aerobic a quatic metabolism, and aqueous photolysis. All other studies are conducted with phenyl radiolabel only (ie., hydrolysis, soil photolysis, other aerobic soil metabolism (MRID: 46246512 only), anaerobic aquatic metabolism). The 1,2,4

- triazole degradate is not able to be detected in studies using the phenyl radiolabel. Field studies not radiolabelled. The only degradates tracked in field studies are: prothioconazole

- desthio, prothioconazole

- S

- methyl, prothioconazole

- thiazocine, and 1,2,4

- triazole. Maximum concentrations in the field studies are determined after the 6 th (CA, NY) or 2 nd (GA) application. (DAT= days after 6 th or 2 nd treatment); 800 ug/kg, 400 ug/kg, and 1000 ug/kg total prothioconazole applied in CA, GA, and NY, respectively.

### 20 

# 6. Receptors

Based on the registered uses of prothioconazole, aquatic and terrestrial non

- target organisms are likely to be exposed to the chemical and/or its degradates. Although incomplete, the toxicity profile s for prothioconazole, prothio conazole

- desthio and pr othioconazole

- S

- methyl indicate that
p rothioconazole and the degradate prothioconazole

- desthio are characterized as being practically

non

- toxic to birds, mammals, and honeybees ( Apis mellifera ), and slightly

- to

- moderately toxic to fish on an acute exposure basis. Based on a limited set of aquatic toxicity data for prothioconazole

- S

- methyl, it appears to be equally toxic to fish and freshwater invertebrates compared to prothiocon a zole

- desthio and prothioconazole on an acute exposure basis . C hronic aquatic toxicity data are not available for prothioconazole

- S

- methyl

. The degradate 1,2,4

- triazole is less toxic than the parent compound to the few taxa for which data are available, with the exception of birds (acute exposure). In contr ast, t he degradate p rothioconazole

- desthio is highly toxic to estuarine/marine invertebrates on an acute exposure basis

. Data for prothioconazole and prothioconazole

- desthio do not indicate that either compound bioconcentrate s in fish.

Tables 4

- 8 provide a summary of the aquatic and terrestrial taxonomic groups, respectively, and most sensitive surrogate species tested to characterize the potential acute and chronic ecological effects of prothioconazole, prothioconazole

- desthio and prothioconazole

- S

- methy l

. No toxicity data were submitted or identified in the open literature for other degradates. Table 4 provides a summary of the toxicity data for the parent compound, prothioconazole, for aquatic organisms. Table 5 provides a summary of the toxicity data for the degradate prothioconazole

desthio for aquatic organisms. Table 6 provides a summary of the toxicity data for the degradate prothioconazole

- S

- methyl for aquatic organisms. Table 7 provides a summary of the to xicity data for the parent compound, prothioconazole, for terrestrial organisms. Finally, Table 8 provides a summary of the available toxicity data for the degradate, prothioconazole

- desthio, for terrestrial organisms. Finally, toxicity data for the 1,2,4

- Triazole degradate is summarized in Tables 9 and 10

. A listing of all of the available toxicity studies for prothioconazole and degradates, including registrant

- submitted studies are provided in Appendix B

.



## a. **Effects to Aquatic Organisms**

Aquatic toxicity data for animals and plants exposed to prothioconazole and its degradates are summarized in Tables 4

- 6 , respectively.

For aquatic fr eshwater fish and invertebrates , prothioconazole and its degradates prothioconazole

- desthio and prothioc onazole

- S

- methyl are all moderately toxic on an acute exposure basis

. For estuarine/marine invertebrates, the degradate prothioconazole

- desthio is very highly toxic under acute exposure conditions

. I n contrast, prothioconazole (parent) and prothioconazol e

- S

- methyl are moderately toxic to freshwater invertebrates

. It is likely that under the conditions of chronic aquatic toxicity tests, most of the prothioconazole parent compound degrades into prothioconazole

- desthio and/or prothioconazole

S

- methyl (see Section 5.a., Transformation Products ). Therefore, many key chronic toxicity

### 21 data on the parent compound are absent. However, important chronic aquatic toxicity data for the major degradate prothioconazole

- desthio are available. Fewer chronic aquatic to xicity data are available for prothioconazole S

- methyl.

On a chronic exposure basis, prothioconazole

- desthio results in reduced larval/juvenile survival, spawning frequency, and growth of fathead minnows ( Pimephales promelas ) and reduced offspring production in water fleas ( Daphnia magna )

. Data are needed to better understand toxicity to sediment dwelling organisms.

Aquatic plants appear particularly sensitive to both the parent and prothioconazole

desthio

. The freshwater aquatic plant duckweed ( Lemna gibba ) and estuarine /marine diatom ( Skeletonema costatum ) are very sensitive to the parent compound. C omparative aquatic plant data are not available for prothioconazole

- desthio or prothioconazole

- S

- methyl. Given the high sensitivity of aquatic plant s to prothioconazole

- desthio, estuarine/marine aquatic plant data are warranted to inform a more comprehensive aquatic plant risk assessment.

Table 4

. Prothioconazole: Toxicity Data for Aquatic Organisms

Taxonomic

Group Study Type Surrogate Species Toxici ty Value (all units in terms of measured active ingredient) Acute Toxicity Classification Source MRID; (Test Substance) Study Classification

Freshwater Fish 96

- Hour Acute Toxicity Rainbow trout
( Oncorhynchus mykiss ) 96

- hr LC 50 =1.83 mg a.i./L Moderately Toxic 46246018 (TGAI) Acceptable

96

- hr LC 50 = 1.69 mg a.i./L Moderately Toxic 46246019 (TEP) Acceptable

Bluegill ( Lepomis macrochirus ) 96

- hr LC 50 =4.59 mg a.i./L Moderately Toxic 46246022 (TGAI) Acceptable

96

- hr LC 50 =5.53 mg a.i./L Moderately Toxic 46246023 (TEP , 41% a.i.) Acceptable

Common Carp ( Cyprinus carpio ) 96

- hr LC 50 =6.42 mg a.i./L Moderately Toxic 46246025 (TGAI) Supplemental

Bioconcentration and Biotransformation Bluegill ( Lepomis macrochirus ) Does not bioaccumulate in fish. N/A 46246034 Supplemental

Freshwater Invertebrates Acute Toxicity

Water Flea ( Daphnia magna ) EC 50 =1.20 mg a.i./L Moderately Toxic 46246009 (TGAI) Acceptable

EC 50 =4.1 mg a.i./L Moderately Toxic 46246010 (TEP , 41% a.i. ) Supplemental

Chronic Toxicity NOAEC=0.51 mg a.i./L (Reproduction, growth) N/A 46246028 (TGAI) Acceptable

Midge Chironomus

riparius NOAEC=0.985 mg a.i./L (pore water)

(Emergence) N/A 46246131 Supplemental

### 22 Taxonomic

Group Study Type Surrogate Species Toxici ty Value (all units in terms of measured active ingredient) Acute Toxicity Classification Source MRID; (Test Substance) Study Classification

Estuarine/ Marine Fish 96

- Hour Acute Toxicity Sheepshead minnow
Cyprinodon variegatus LC 50 >10.3 mg a.i./L Slightly Toxic 46246027 (TGAI) Acceptable

Early Life Stage Toxicity

(28

- d) No Data

Estuarine/

Marine Invertebrates 96

- Hour Shell Deposition Eastern oyster

Crassostrea

virginica EC 50 =3.0 mg a.i./L Moderately Toxic 46246014 (TGAI) Acceptable

Acute Toxicity Mysid
Americamysis bahia ( formerly

Mysidopsis

bahia) EC 50 =2.4 mg a.i./L Moderately Toxic 46246016 (TGAI) Acceptable

Aquatic Plants 7

- Day Toxicity Duckweed ( Lemna gibba ) EC 50 =0.073 mg a.i./L
NOAEC=0.003 mg a.i./L
(Frond number) N/A 46246101 (TGAI) Acceptable

EC 50 =0.110 mg a.i./L

NOAEC=0.0075 mg a.i./L
(Frond number) N/A 46246102 (TEP , 41% a.i. ) Acceptable

96

- Hour Toxicity Blue

- green algae ( Anabaena flos

aquae ) EC 50 =3.5 mg a.i./L
NOAEC=0.82 mg a.i./L
(Cell density) N/A 46246103 (TGAI) Acceptable

96

- Hour Toxicity Green Algae ( S elenestrum capricornutum ) EC 50 =0.88 mg a.i./L
NOAEC=0.371 mg a.i./L
(Cell density) N/A 46246105 (TGAI) Acceptable

Freshwater alga ( Pseudokirchneri ella subcapitata ) ( formerly Selenastrum capricornutum) EC 50 =1.1 mg a.i./L
NOAEC=0.48 mg a.i./L
(Cell density) N/A 46246106 (TEP) Acceptable

### 23 Taxonomic

Group Study Type Surrogate Species Toxici ty Value (all units in terms of measured active ingredient) Acute Toxicity Classification Source MRID; (Test Substance) Study Classification

Aquatic Plants 96

- Hour Toxicity Freshwater Diatom ( Navicula pelliculosa ) EC 50 =0.180 mg a.i./L

EC 05 =0.06 mg a.i./L

NOAEC: Not

determined
(Biomass) N/A 46246109 (TGAI) Acceptable

Estuarine/marine Diatom ( Skeletonema

costatum ) EC 50 =0.021 mg a.i./L

NOAEC=0.0073 mg a.i./L
(Biomass) N/A 46246110 (TGAI) Acceptable



### Table 5 . Prothioconazole

- Desthio : Toxicity Data for Aquatic Organisms

Taxonomic

Group Study Type Species Toxicity Value (all units in terms of measured degradate ) Acute Toxicity Classification Source (MRID) Study Classification

Freshwater Fish 96

- Hour Acute Toxicity Rainbow trout ( Oncorhynchus mykiss ) 96

- hr LC 50 = 5.94
mg /L Moderately Toxic 46246020 Acceptable

Fathead Minnow

( Pimephales promelas ) 96

- hr LC 50 =11.4
mg /L Slightly Toxic 46246026 Acceptable

Full Life Cycle Toxicity Fathead minnow ( Pimephales promelas ) NOAEC= 0.148

m g /L LOAEC= 0. 296

m g /L (Survival, spawning frequency, growth, deformities) N/A 46246033 Supplemental

Freshwater Invertebrates Chronic Toxicity Water Flea ( Daphnia magna ) NOAEC=0.103
mg /L LOAEC= 0.206 mg/L (Offspring production) N/A 46246029 Acceptable

Midge ( Chironomus

riparius ) NOAEC=0.34 mg /L (pore water)
LOAEC=0.64 mg/L
(Emergence) N/A 47626901 Supplemental

Estuarine /

Marine Invertebrates Acute Toxicity LC 50 =0.06 mg /L Very Highly Toxic 46246017 Acceptable

### 24 Taxonomic

Group Study Type Species Toxicity Value (all units in terms of measured degradate ) Acute Toxicity Classification Source (MRID) Study Classification

Chronic Toxicity Mysid
( Americamysis bahia ) ( f ormerly Mysidopsis

bahia ) NOAEC=0.064
mg /L

LOAEC= 0.128 mg/L
(Reproduction) N/A 46246030 Acceptable

Estuarine/ Marine Fish 96

- Hour Acute Toxicity No Data

Early Life Stage Toxicity (28

- Day) No Data

Aquatic Plants 7

- Day Study Duckweed ( Lemna gibba ) EC 50 =0.035 mg /L NOAEC=0.0058
mg /L (Frond number) N/A 46246104 Acceptable

96

- Hour Toxicity Green Algae ( S cenedesmus subspicatus ) EC 50 =0.074 mg/L EC 05 =0.011 mg /L

NOAEC : Not determined (<0.011
mg /L) ( Cell density )

46246010 N/A 46246108 Acceptable

Freshwater Fish Bioconcentration and Biotransformation Bluegill ( Lepomis macrochirus ) Does not bioaccumulate in fish. N/A 46246035 Acceptable



### Table 6 . Prothioconazole

- S

- Methyl : Summary of Toxicity Data for Aquatic Organisms

Taxonomic

Group Study Type Species Toxicity Value (all units in terms of measured degradate ) Acute Toxicity Classification Source (MRID) Study Classification

Freshwater Fish Acute Toxicity Rainbow trout Oncorhynchus mykiss 96

- hr LC 50 = 1.78
mg /L Moderately Toxic 46246021 Acceptable

Full Life Cycle Toxicity Fathead minnow Pimephales promelas No Data

Freshwater Invertebrates Acute Toxicity Water Flea ( Daphnia magna ) EC 50 =2.7 mg /L Moderately Toxic 46246012 Acceptable

### 25 Taxonomic

Group Study Type Species Toxicity Value (all units in terms of measured degradate ) Acute Toxicity Classification Source (MRID) Study Classification

Acute Toxicity Midge Chironomus

riparius No Data

Chronic Effects on

Midge Larvae (28

- d) No Data

Estuarine/ Marine Fish 96

- Hour Acute Toxicity Sheepshead minnow
Cyprinodon variegatus No Data

Aquatic Plants 96

- Hour Toxicity Green Algae
( S elenestrum capricornutum ) EC 50 =2.8 mg /L NOAEC=Not

determined N/A 46246107 Supplemental



## b. **Effects to Terrestrial Organisms**

Toxicity values for terrestrial animals and plants are summarized in Tables 7 and 8

, respectively.

Prothioconazo le and its degradate prothioconazole

- desthio are , for the most part, practical ly non

- toxic to mammals and birds under acute exposure conditions. Prothioconazole is practically non

- toxic to adult honey bees on an acute exposure basis. Acute toxicity data for honey bees are lacking for prothioconazole

- desthio. There are no terre strial ecotoxicity data for prot hioconazole

- S

- methyl ( degradate )

. In general, prothioconazole

- desthio appears to be more toxic to terrestrial organisms than the parent compound. In birds, 70% mortality was observed in bobwhite quail in the acute dietary study involving exposure to prot hioconazole

- desthio at the highest exposure level, and the compound is classified as slightly toxic to birds on an acute exposure basis . Sub

- lethal effects including decreased body weight and clinical toxicity were observed in the acute avian oral and diet ary studies with prothioconazole

- desthio . In chronic avian studies, no significant effects of the parent or degradates were reported at concentrations up to 449 mg/kg. In chronic mammalian tests on prothioconazole

- desthio, reproductive effects including d ecreased pup viability and decreased pup weight were observed at a LOAEL of 640 mg/kg

- diet with a corresponding NOAEL of 160 mg/kg

- diet. The NOAEL is equivalent to a dose of 9.5 mg/kg bw/day in female
rats.

Tier I plant studies were conducted with 10 species of plants exposed to 0.272 lbs a.i./A, which is greater than the maximum single application rate of 0.178 lbs a.i./A. With the exception of cuc umbers, effects did not exceed 25% inhibition. For cucumber plants, there was a greater

### 26 than 25% effect on shoot length and dry weight in the seedling emergence study. Although effects in cucumbers did not exceed 25% in the vegetative vigor study, the percent inhibition for this species was generally among the hi ghest. Based on the results of the Tier I study, a Tier II study for cucumber was required.

In the Tier II seedling emergence study, no effects exceeded a 25% inhibition compared to control for cucumbers for the highest test concentration of 0.272 lbs a. i./A. However, there were significant effects on both shoot height and dry weight with the lowest NOAEC associated with shoot height. The NOAEC and EC 05 

### for shoot height are equivalent to application rates of 0.03 and 0.08 lbs a.i./A, respectively; the N OAEC is used to calculate RQs for listed plants while the EC 25 

### is used for non

- listed plants

.

Table 7

. Prothioconazole : Toxicity Data for Terrestrial Organisms

Taxonomic

Group Study Type Surrogate Species Toxicity Value (all units in terms of measured active ingredient) Acute Toxicity Classification Source MRID;

(Test Substance) Study Classification

Birds Acute Toxicity Bobwhite Quail ( Colinus virginianus ) LD 50 >2000 mg a.i./kg bw Practically Non

- Toxic 46246036 (TGAI) Acceptable

Canary ( Serinus canaria ) LD 50 >2000 mg a.i./kg

- bw Practically Non

- Toxic 48024801 (TGAI) Acceptable

Sub

- Acute Toxicity Bobwhite Quail ( Colinus virginianus ) LC 50 >4983 mg a.i./kg

- diet Practically

non

- toxic 46246038 (TGAI) Acceptable

Mallard Duck ( Anas platyrhynchus ) LC 50 >5567 mg a.i./kg

- diet Practically

non

- toxic 46246040 (TGAI) Acceptable

Reproduction

Toxicity Bobwhite Quail ( Colinus virginianus ) NOAEC=982 mg a.i./kg

- diet (LOAEC>982 mg a.i./kg

- diet) N/A 46246042 (TGAI) Acceptable

Mallard Duck ( Anas platyrhynchus ) NOAEC=1978 mg a.i./kg

- diet (LOAEC>1978 mg a.i./kg

- diet) N/A 46246044 (TGAI) Acceptable

Mammals Acute Oral Toxicity

Norway Rat ( Rattus norvegicus ) LD 50 ≥6200 mg/kg Practically Non

- Toxic 46246230 Acceptable

Acute Inhalation Toxicity LC 50 ≥ 4.99 mg/L Toxicity Category 4 46246246 Acceptable

2

- Generation

Mammal Reproduction

Toxicity NOAEL = 100 mg a.i./kg/day LOAEC=750 mg a.i./kg/day (decreased number

and duration of estrus cycles) N/A 46246334 Acceptable

Terrestrial Invertebrates Acute Adult Honey Bee Contact Toxicity
Honey bee ( Apis mellifera ) LD 50 >200 μg a.i. /bee Practically Non

- Toxic 46246046 (TEP) Acceptable Acute Oral

Toxicity LD 50 >232 μg a.i. /bee Acute Contact Toxicity LD 50 >200 μg a.i./bee 46246048 (TGAI) Acceptable

Acute Oral

Toxicity LD 50 >71 μg a.i./bee Practically Non

- Toxic Supplemental

### 27 Taxonomic

Group Study Type Surrogate Species Toxicity Value (all units in terms of measured active ingredient) Acute Toxicity Classification Source MRID;

(Test Substance) Study Classification

Terrestrial

Plants Tier 1 Seedling Emergence Buckwheat, Corn, Onion, Ryegrass, Wheat, Cucumber, Soybean, Sunflower, Tomato, Turnip EC 25 >0.272 lb a.i./A NOAEC=0.272 lb a.i./A [Except: Cucumber;

EC 25 <0.272 lb a.i./A; NOAEC=<0.272 lb a.i./A)] N/A

46246049 (TEP, 41% a.i.) Acceptable

Tier 1 Vegetative Vigor N/A Acceptable

Tier 2 Seedling

Emergence Cucumber NOAEC=0.03 lb a.i./A EC 2 5 > 0. 272 lb a.i./A (Shoot height) N/A 46246050 (TEP , 41% a.i.) ) Acceptable



### Table 8

. Prothioconazole

- D esthio : Toxicity Data for Terrestrial Organisms

Taxonomic

Group Study Type Surrogate Species Toxicity Value (all units in terms of measured degradate ) Acute Toxicity Classification Source MRID;

(Test Substance) Study Classification

Birds Acute Toxicity

Bobwhite Quail ( Colinus virginianus ) LD 50 >2000 mg/kg

bw Practically Non

- Toxic 46246037 Acceptable

Sub

- Acute Toxicity (8

- Day study) LC 50 = 4252 mg /kg

bw Slightly Toxic 46246039 Acceptable

Reproduction

Toxicity NOAEC= 506.7 mg/kg

- diet LOAEC>506.7

mg /kg

- diet N/A 46246043 Acceptable

Mallard Duck ( Anas platyrhynchus ) NOAEC=449
mg /kg

- diet (LOAEC>449

mg/kg

- diet) N/A 46246045 Supplemental (I ssues with degradation of test substance )

Mammals Acute Oral Toxicity

Norway Rat ( Rattus norvegicus ) LD 50 =2806 mg /kg Practically Non

- Toxic 46246231 Acceptable

Acute Inhalation Toxicity LC 50 ≥ 5.08 mg/L Toxicity Category 4 46246247 Acceptable

2

- Generation

Mammal Reproduction

Toxicity NOAEL=10.4
mg /kg/day LOAEL= 42.6

mg/kg/day (decreased viability of pups) N/A 46246333 Acceptable

Terrestrial Invertebrates Acute Oral Toxicity Honey bee ( Apis mellifera ) No Data Acute Contact Toxicity



## Toxicity of Prothioconazole Degradate: 1,2,4

**- Triazole** 

Available guideline data for the degradate of prothioconazole

- 1,2,4

- triazole (PC 600074) are presented in Table 9 and 10

. To compare the toxicity of the degradate 1,2,4

- triazole to the

### 28 parent prothioconazole, a molecular weight conversion was completed to determine if 1,2,4

- triazole was more/less or equally as toxic to aquatic and terrestrial organisms as the parent prothioconazole. Based on the available toxicity data, 1,2,4

- triazole is less toxic than prothioconazole to non

- vascular plants (green alga e), freshwater fish (acute basis), and freshwater invertebrates (acute basis). Birds however, appear to be more sensitive to 1,2,4

- triazole compared
to the parent prothioconazole. Finally, 1,2,4

- triazole is less toxic than prothioconazole to mammals on a chronic exposure basis. H owever, there is uncertainty about the relative chronic toxicity to mammals for the two compounds because a NOAEC was established in the prothioconazole study ( 100 mg ai/kg

- diet) whereas the 1,2,4

- triazole study did not test below 250 mg ai/kg

- diet. Therefore, an accurate comparison to the toxicity of the parent and degradate cannot be completed.

The 1,2,4

- triazole showed chronic effects to mammals at 250 mg ai/kg

- diet (15 mg/kg

bw); however, there is uncertainty about the relat ive chronic toxicity because a NOAEC was not established as the 1,2,4

- triazole study did not test below 250 mg ai/kg

- diet. Observed effects in adults included dec r eases in male body weight in F1 males, decrease s in spleen weight in F1 females, cerebellar lesions and decreases in brain and thyroid weight. Offspring effects included decreases in body weight, impacts on brain weight in F2 pups, and decreased spleen weight in F2 female pups. Reproductive effects were also noted and included abnormal sperm an d decreases in the number of corpora lutea in F1 females, reproductive failure (no viable offspring, and increases in corpora lutea in F0 parental females )

.

Non

- guideline, summary report data on acute oral toxicity to rats suggests that 1,2,4

- triazole (LD 50 

### s ranging from 1375 to 3080 mg/kg bw) and prothioconazole (LD 50 

### > 6200 mg ai/kg bw) are practically non

- toxic on an acute exposure basis.

Table 9

. Summary of Aquatic Toxicity Data for Prothioconazole Degradate 1,2,4

- Triazole Type of Study Species Toxicity Value MRID #

Acute

– Freshwater Fish Rainbow trout ( S. gairdneri ) 96

- hr LC 50 = 498 mg a.i./L 1 (2483 mg a.i./L ) 2 (practically non

- toxic) 48474301

Acute

– Freshwater Invertebrate Water flea ( D. magna ) 48

- hr EC 50 > 98.1 mg a.i./L 1 (> 489 mg a.i./L ) 2 (practically non

- toxic) 48453206

Non

- vascular Aquatic Plant Freshwater Algae ( P. subcapitata ) 96

- hr EC 50 = 14 mg a.i./L 1 (69.8 mg a.i./L ) 2 45880401

1 Expressed in terms of 1,2,4

- triazole

2 Exp ressed in terms of prothioconazole

– A conversion is made from 1,2,4

- triazole to prothioconazole on a molecular weight basis. Multiply 1,2,4

- triazole toxicity endpoint (e.g., LD 50 value) by the ratio of the molecular weight of prothioconazole divided by the molecular weight 1,2,4

- triazole (3 44.3 g/mol/69.0635 g/mol = 4. 985 ).



### Table 10

. Summary of Terrestrial Toxicity Data for Prothioconazole Degradate 1,2,4

- Triazole Type of Study Species Toxicity Value MRID #

Acute

– Avian Oral Dose Bobwhite quail ( C. virginianus ) LD 50 = 770 mg ai/kg

- bw 1 (slightly toxic) (3839 mg ai/kg

- bw) 2 (practically non

- toxic) 49380701

Two Generation Reproduction

– Mammalian Laboratory rat ( R. norvegicus ) NOAEC < 250 mg ai/kg

- diet 1 LOAEC ≤ 250 mg ai/kg

- diet 1 (< 1246 mg ai/kg

- diet) 2 Most sensitive effects were decreased bodyweight and decreased bodyweight gain in the parents and in the offspring. 46467304

### 29 Type of Study Species Toxicity Value MRID #

Subchronic (28 day adult) and reproductive (additional 28 day offspring)

– Terrestrial Invertebrate Earthworm ( E. fetida ) LC 50 > 0.07081 mg/kg 1 (> 0.3530 mg/kg) 2 NOAEC ≥ 0.07081 mg/kg 1 (≥0.3530 mg/kg) 2 LOAEC > 0.07081 mg/kg No significant effects observed (mortality, behavior, bw, reproduction or food consumption in any trmt group) 45880402

28 day

– Terrestrial Invertebrate Springtails ( Folsomia candida ) 28

- day LC 50 > 10 mg ai/kg soil 1 (> 49.85 mg ai/kg soil) 2 NOAEC = 1.8 mg ai/kg soil (8.973 mg ai/kg soil) 2 LOAEC = 3.2 mg ai/kg soil based on reduced number of juveniles 45880404

1 Expressed in terms of 1,2,4

- triazole

2 Expressed in terms of prothioconazole

– A conversion is made from 1,2,4

- triazole to prothioconazole on a molecular weight basis. Multiply 1,2,4

- triazole toxicity endpoint (e.g., LD 50 value) by the ratio of the molecular weight of prothioconazole divided by the molecular weight 1,2,4

- triazole (344.3 g/mol/69.0635 g/mol = 4.985).



## c. **Ecological Incidents**

During the risk assessment process, the risk assessor will incorporate information from ecological incident reports by searching the most recent information available. Databases that will be queried include the E cological I ncident I nformation S ystem (EIIS) , the Avian Monitoring System (AIMS) and the OPP Aggregate Incident Database (IDS)

. EIIS is an OPP database that houses ecological incidents that have been reported to the Agency. When available, EIIS includes date and location of an incident, type and magnitude of effects observed in various species, use(s) of pesticides known or sus pected of contributing to the incident, and results of any chemical residue analysis or other analyses conducted during incident investigation. EIIS incidents are categorized according to the certainty that the incident resulte d from pesticide exposure. AIMS is a database administered by the American Bird Conservancy that contains publicly available data on reported avian incidents involving pesticides. The Aggregate Incident Reports database is an Agency database that may contain minor wildlife and plan t incidents for chemicals. Based on a search conducted August 12, 2015, there were no reported incidents for prothioconazole in the AIMS database.

As of August 27, 2015

, EIIS contains a total of 15 plant incidents for prothioconazole. No reports were f ound for the degradates 1,2,4

- triazole, prothioconazole

- desthio or prothioconazole

S

- methyl. For prothioconazole (parent compound), p lant damage was reported most often in peanuts, but was also reported in corn, soybean, wheat, sorghum and general agricult ural areas in Georgia, Minnesota, Illinois, Iowa, Flo rida and North Dakota. All were classified as “ p ossible” certainty. See Appendix C for a summary table of the incidents from EIIS.

OPP's IDS includes reports of pesticide incidents from various sources, including mandatory Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) Section 6(a)(2) reports from registrants, other federal and state health and environmental agencies, and individual consumers. Since 1992, OPP has compiled these reports in IDS . IDS contains reports from across the U.S. and most incidents have all relevant product information recorded. This system stores incident data and includes information about the location, date and nature of the incident. IDS was

### 30 searched August 12, 2015 and returned 8 total ecological incident reports between 1997 and 2013. These were reports for minor plant damage caused by prothioconazole,

The lack of reported incidences should not be construed as the absence of incidents. I ncident reports for non

- target organisms typically provide information only on mortality events and plant damage. Sublethal effects in organisms such as abnormal behavior, reduced growth and/or impaired reproduction are rarely reported, except for phytoto xic effects in terrestrial plants.



# 7. Exposure Pathways of Concern

The environmental fate properties and use patterns of prothioconazole indicate that there are multiple potential transport mechanisms of prothioconazole and its degradates to aquatic and
te rrestrial organisms.

For a pesticide to pose an ecological risk, it must reach ecological receptors in biologically significant concentrations. An exposure pathway is the means by which a pesticide moves in the environment from a source to an ecologica l receptor. For an ecological pathway to be complete, it must include a source, a release mechanism, an environmental transport medium, a point of exposure for ecological receptors, and a feasible route of exposure.

The environmental fate properties of prothioconazole and its degradates indicate the following transport mechanisms for potential exposure to aquatic (including those dwelling in sediment) and terrestrial organisms:

• Direct contact

• Spray drift

• Runoff

• Leaching to groundwater

• Consumption of co ntaminated food (sprayed food or treated seeds)

• Consumption of contaminated water

• Root uptake (plants)

• Exposure to sediment

• Irrigation water

Drinking water and inhalation exposure pathways were screened using the SIP (Screening Imbibition Program) and ST IR (Screening Tool for Inhalation Risk) screening methods.

For the parent compound, prothioconazole, d rinking water alone was found to be a potential concern for birds on both an acute and chronic exposure basis (no concern for mammals)

. For the degradate prothioconazole

- desthio, drinking water alone is a concern for birds (both acute and chronic exposure basis) and mammals (chronic exposure basis only). Results for those pathways that result in risks of concern are displayed below in Tabl es 11 and 12

. However, inhalation exposure was found to be an exposure pathway of low concern for the parent compound ( prothioconazole ), as well as the prothioconazole

- desthio and 1,2,4

- triazole degradates for both mammals and birds (no LOC exceedances a re expected). See Appendices D

### 31 and E for example SIP and STIR results. SIP and STIR are described in detail at: http://www.epa.gov/oppefed1/models/terrestrial/index.htm

.

T able 11

. SIP Results for Prothioconazole (Parent Compound)
Avian Results Parameter Acute Chronic Upper bound exposure (mg/kg

- bw) 278.6400 278.6400 Adjusted toxicity value (mg/kg

- bw) 1440.8590 48.7195 Ratio of exposure to acute toxicity 0.1934 5.7193

Conclusion* Exposure through drinking water alone is a potential concern for birds Exposure through drinking water alone is a potential concern for birds

*Conclusion is for drinking water exposure alone. This does not combine all routes of exposure. Therefore, when aggregated with other routes ( i.e ., diet, inhalation, dermal), pesticide exposure through drinking water may contribute to a total exposure that has potential for effects to non

- target animals.



### Table 12

. SIP Results for Prothioconazole

- Desthio (Degradate)
Mammal Results
Parameter Acute Chronic Upper bound exposure (mg/kg

- bw) 59.1680 59.1680 Adjusted toxicity value (mg/kg

- bw) 2158.2646 7.9993 Ratio of exposure to toxicity 0.0274 7.3967

Conclusion* Drinking water exposure alone is NOT a potential concern for mammals Exposure through drinking water alone is a potential concern for mammals

Avian Results

Parameter Acute Chronic Upper bound exposure (mg/kg

- bw) 278.6400 278.6400 Adjusted toxicity value (mg/kg

- bw) 1440.8590 25.1040

Ratio of exposure to acute toxicity 0.1934 11.0994

Conclusion* Exposure through drinking water alone is a potential concern for birds Exposure through drinking water alone is a potential concern for birds

*Conclusion is for drinking water exposure alone. This does not combine all routes of exposure. Therefore, when aggregated with other routes ( i.e ., diet, inhalation, dermal), pesticide exposure through drinking water may contribute to a total exposure that has potential fo r effects to non

- target animals.

### 32 

# 8. Analysis Plan

**a. Stressors of Concern** 

i. Ecological Risk Assessment

The stressors of ecologic al concern for terrestrial and aquatic organisms are prothioconazole and two of the major degradates

, prothioconazole

- desthio and prothioconazole

- S

methyl including the 1,2,4

- triazole degradate and unextracted material

. Because a TTR approach will be used to evaluate potential terrestrial and aquatic risks, the lowest (most sensitive) available toxicity value for each taxon will be used to calculate RQs.

Using the TTR approach, risk will be calculated using the lowest or most sensitive toxicity value (most ecologically protective) available for either the parent prothioconazole compound

, prothioconazo le

- desthio or prothioconazole

- S

- methyl . For example, in calculating acute RQs for aquatic invertebrates, exposure would be compared to the LC 50 

### for prothio conazole

- desthio, which has the lowest acute toxicity value ( 0.06 mg/L ) for aquatic invertebrates.

Neither acute nor chronic toxicity data are available for prothioconazole

- S

- methyl for estuarine/marine fish and invertebrates. Acute estuarine/marine invertebrate data are requested for prothioconazole

- S

- methyl. More data are also needed to complete the t oxicity profile for prothioconazole and prothioconazole

- desthio. Specifically, sediment toxicity data are needed for prothioconazole and its degradates (See Section 11 ). In the absence of these data, risk will be presumed where there is exposure to non

- tar get organisms.

Although 1,2,4

- triazole is a major degradate identified in the submitted aqueous photolysis (11%) and aerobic aquatic metabolism (41%) studies, it is only present at <2% in aerobic soil metabolism studies. Given the persistence of the TTR based on the parent and the two major degradates previously identified, the inclusion of 1,2,4

- triazole is not expected to significantly alter the estimated exposure levels or impact risk. At this time it is anticipated that a separate risk assessment wi ll be conducted on 1,2,4

- triazole degradate, perhaps similar to the aggregate drinking water assessment completed for the triazole

- derivative fungicides during the registration review process . The Office of Pesticide Program’s Health Effects Division (HED ) has conducted aggregate human health risk assessments for 1,2,4

- triazole and triazole conjugates, (USEPA 2006 b ; D322215). However, an ecological risk assessment for 1,2,4

- triazole has not been conducted as of this date.

ii. Drinking Water

The drinking water assessment (DWA) conducted to support the Registration R eview human health risk assessments of prothioconazole will incorporate model estimates of prothioconazole residues of concern, which comprise parent compound (including unextracted residues, wh ich may be parent)

, prothioconazole

- desthio, and prothioconazole

- S

- methyl (USEPA, 2006 a ; USEPA, 2012 c ), in surface water and groundwater. The prothioconazole residues of concern may be reevaluated pending receipt and review of additional environmental fate and toxicity data for prothioconazole and its degradates. The degradate 1,2

- 4 t riazole is assessed separately because the compound has toxicity endpoints t hat are different from those of

### 33 prothioconazole . In the absence of toxicity data, prothioconazole

- desthio and prothioconazole

- S

methyl are assumed to have similar toxicity to prothioconazole

. Therefore, as in past EFED assessments, the EDWCs are based on TTR , i.e., the parent prothioconazole compound plus prothioconazole

- desthio and prothioconazole

- S

- methyl including unextracted material, as discussed in USEPA

, 2006 c

. It is anticipated that the DWA will be updated to include any new environmental fate da ta received by the Agency; specifically, it is anticipated that additional metabolism data will be used to amend modeling inputs. Additionally, the DWA will be updated using any new exposure models implemented since the last DWA was conducted.



## b. **Measures of Exposure** 

EFED will use standard available models to evaluate potential exposures to aquatic and terrestrial organisms as described at http://www2.epa.gov/pesticide

- science

- and

- assessing

pesticide

- risks/models

- and

- databases

- used

- pesticide

- risk

- assessment#models

. Screening level calculations have suggested that drinking water may be a significant exposure pathway for birds, although not for mammals

. Inhalation exposure is not expected to represent a significant exposure pathway for ei ther birds or mammals

. These exposure pathways

, and any others that are relevant may be further considered at the time of the risk assessment ( Appendi ces C and D )

. Available Monitoring Data

No monitoring data for prothioconazole were identified. Neither the United States Geological Survey (USGS) NAWQA program nor the California Department of Pesticide Regulation (CDPR) include prothioconazole in their monitoring programs.



## c. **Measures of Effect**

Toxicity data presented in Section 6 of this problem formulation will be used to calculate risk quotients. Any additional information submitted by the registrant or found in the open literature prior to conduct of the risk assessment will also be considered. The open literature studies are identified using EPA’s ECOTOXicology database ( ECOTOX) ( USEPA, 200 9a ), which employs a literature search engine for locating chemical toxicity data for aquatic life, terrestrial plants, and wildlife. The evaluation of both sources of data can also provide insight into the direct and indirect effects of pesticides on biotic communities from loss of species that are sensitive to the chemical s and from changes in structure and functional characteristic s of the affected communities.



## 9. **Endangered Species Assessme nts** 

Consistent with EPA’s responsibility under the Endangered Species Act (ESA), the Agency will evaluate risks to federally listed threatened and endangered (listed) species from registered uses of pesticides in accordance with the Joint Interim Approach es developed to implement the recommendations of the April 2013 National Academy of Sciences (NAS) report, Assessing Risks to Endangered and Threatened Species from Pesticides

. The NAS report outlines

### 34 recommendations on specific scientific and technical i ssues related to the development of pesticide risk assessments that EPA and the Services must conduct in connection with their obligations under the ESA and FIFRA ( http://www2.epa.gov/endangered

- species/implementing

nas

- report

- recommendations

- ecological

- risk

- assessment

- endangered

- and )

. EPA will address concerns specific to prothioconazole in connection wit h the developmen t of its final R egistration R eview decision for prothioconazole.

In November 2013, EPA, the U.S. Fish and Wildlife Service, National Marine Fisheries (the Services), and USDA released a white paper containing a summary of their joint Interim Approaches for assessing risks to listed species from pesticides. These Interim Approaches were developed jointly by the agencies in response to the NAS recommendations, and reflect a common approach to risk assessment shared by the agencies as a way of addressing s cientific differences between the EPA and the Services. Details of the joint Interim Approaches are contained in the November 1, 2013 white paper , Interim Approaches for National

- Level Pesticide Endangered Species Act Assessments Based on the Recommendati ons of the National Academy of Sciences April 2013 Report ( http://www2.epa.gov/endangered

- species/interim

- approaches

pes ticide

- endangered

- species

- act

- assessments

- based

- nas

- report )

. Given that the agencies are continuing to develop and work toward implementation of the Interim Approaches to assess the potential risks of pesticides to listed species and their designated critical habitat, this ecological problem formulation supporting the Preliminary Work Plan for prothioconazole does not describe the specific ESA analysis, including effects determinations for specific listed species or designated critical habitat, to be c onducted during registration review. While the agencies continue to develop a common method for ESA analysis, the planned risk assessment for the registration review of prothioconazole will describe the level of ESA analysis completed for this particular registration review case. This assessment will allow EPA to focus its future evaluations on the types of species where the potential for effects exists, once the scientific methods being developed by the agencies have been fully vetted. Once the agencies h ave fully developed and implemented the scientific methods necessary to complete risk assessments for listed species and their designated critical habitats, these methods will be applied to subsequent analyses of prothioconaz ole as part of completing this R egistration R eview.



## 10. **Endocrine Disruptor Screening Program**

Prothioconazole was not included in the first group of chemicals issued an order to conduct Tier 1 EDSP testing. For additional information the EDSP program, visit http://www.epa.gov/endo/

.


## 11. **Preliminary Identification of Data Gaps**

a. Environmental Fate

Tables 13 and 1 4 identify environmental fate studies by MRID that offer data for each guideline requirement, as well as study classifications and whether or not further data are needed in order to support risk assessment.

### 35 Table 13 . Environmental Fate Data for Prothioconazole.

OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data needed to conduct risk assessment? Justification and Assumptions EPA will Make in Absence of Data

-

Some Example texts are include
835.2120 Hydrolysis 46246505 Acceptable No  ̄

835.2240 Aqueous photolysis 46246507 Supplemental No  ̄

835.2410 Soil photolysis 46246510 Acceptable No  ̄

835.4100 Aerobic soil metabolism 46246511
46246512 Acceptable Yes

, additional data are required for one more soil, with use of more appropriate/ exhaustive extraction s. Guidance is available 1

. Without new useful information, u nextracted residues will be added in as parent for the purposes of determining degradation rates for modeling.

835.4200 Anaerobic soil metabolism No data  ̄ No  ̄

835.4300 Aerobic aquatic metabolism 46246515 Supplemental No  ̄

835.4400 Anaerobic aquatic metabolism 46246516 Supplemental Yes , a dditional data are required for one more sediment/water system, with use of more appropriate/ exhaustive extractions. Guidance is available 1

. Without new useful information, u nextracted residues will be added in as parent for the purposes of determining de gradation rates for modeling. Without additional data, f or modeling, the single half

- life value will be multiplied by 3 to account

for uncertainty in using a si ngle value.

835.1230 Adsorption/ desorption and leaching (batch EQ) 46246450 Acceptable

No  ̄

835.1240 Adsorption/ desorption and leaching (column leaching) 46246539
46246504 Supplemental

835.1410 Volatility

– laboratory No data No  ̄

835.6100 Terrestrial Field Dissipation & Analytical method in soil 46246517 Supplemental

No  ̄ 46246518 Supplemental

46246519 Supplemental

1 http://www2.epa.gov/pesticide

- science

- and

- assessing

- pesticide

- risks/guidance

- addressing

- unextracted

- pesticide

- residue s

.

### 36 OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data needed to conduct risk assessment? Justification and Assumptions EPA will Make in Absence of Data

-

Some Example texts are include

835.6200 Aquatic field dissipation & Analytical method in water 46246522 Supplemental

No  ̄ 46246523 Supplemental

46246524 Supplemental

850.1730 Fish bioconcentration 46246034
46246035 Supplemental No  ̄



### Table 1 4 . Submitted Environmental Fate Data for the Prothioconazole Degradates, Prothioconazole

desthio and Prothioconazole

- S

- methyl

OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data needed to conduct risk assessment? Justification and Assumptions EPA will Make in Absence of Data

835.2120 Hydrolysis (desthio) 46246506 Supplemental No  ̄

835.1230 Adsorption/ desorption (desthio) 46246450 Acceptable No  ̄

835.1230 Adsorption/ desorption (S

- methyl) 46246501 Acceptable No  ̄

835.4100 Aerobic soil metabolism

(desthio) 46246513 Supplemental No  ̄

835.4100 Aerobic soil metabolism (S

- methyl) 46246514 Supplemental No  ̄



## b. Ecological Effects

Table s 1 5

– 19 id entify ecological effects studies by MRID that offer data for each guideline requirement, as well as study classifications and whether or not further data are needed in order to support risk assessment. Justification for each data need is provided.

Table 1 5

. Prothioconazole: Submitted A quatic E cological E ffects D ata

OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data needed to conduct risk assessment? Justification and Assumptions EPA will Make in Absence of Data

850.1010 Freshwater invertebrate acute toxicity 46246009 Acceptable No 46246010 Supplemental

### 37 OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data needed to conduct risk assessment? Justification and Assumptions EPA will Make in Absence of Data

850.1025 850.1035 850.1045 850.1055 Estuarine/marine invertebrate acute toxicity 46246016 Acceptable
No 46246014 Acceptable

850.1075 Freshwater fish acute toxicity 46246018 Acceptable

No 46246019 Acceptable

46246022 Acceptable

46246023 Acceptable

46246025 Supplemental

850.1075 Estuarine/marine fish acute

toxicity 46246027 Acceptable No

850.1300 Freshwater invertebrate

life cycle 46246028 Acceptable No

850.1350 Estuarine/marine invertebrates

life cycle No Data No

850.1400 Freshwater fish early

- life stage No Data No

### 38 OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data needed to conduct risk assessment? Justification and Assumptions EPA will Make in Absence of Data

850.1400 Estuarine/marine fish early

- life stage No Data No

850.1500 Fish life cycle No Data No

850.1735 Whole sediment: Chronic freshwater invertebrate s No Data Yes , based on the physio

chemical properties of prothioconazole,

these data are

required 2

, 3 Test substance should be the prothioconazole TGAI. For freshwater sediment testing, tests on an amphipod ( e.g., Hyalella azteca) and a midge ( e.g., Chironomus dilutus) are requested. Results should be reported in terms of prothioconazole, prothioconazole

- desthio and prothioconazole

- S

- methyl. A protocol must be submitted for review prior to initiating the studies. In the absence of these data, EFED will make a presumption of risk to sediment

- dwelling organisms.

850.1740 Whole sediment: Chronic marine

invertebrates No Data Yes , based on the physio

chemical properties of prothioconazole,

these data are

required 2, 4 Test substance should be the prothioconazole TGAI. For estuarine/marine sediment testing, tests on one amphipod species is requested ( e.g., Leptocheirus plumulosus ). Results should be reported in terms of prothioconazole, prothioconazole

- desthio and prothioconazole

- S

- methyl. A protocol must be submitted for review prior to initiating the studies. In th e absence of these data, EFED will make a presumption of risk to sediment

- dwelling organisms.

850.1790 Chironomid Sediment Toxicity 46246131 Supplemental No

850.4400 46246101 Acceptable No

2 According to 40 CFR Part 158 Subpart G, pesticide sorption onto sediment particles is considered a trigger for sediment toxic ity testing ( i.e., moderate to high sorption as specified in Figure 1 ) if any of the following conditions exist: 1) The Kd is ≥ 50 L/kg

- solid; 2) The KOC is ≥1000 L/kg

- organic carbon; 3) The log KOW is ≥ 3.
3 ,4 A tiered testing approach may be considered for requesting chronic sediment toxicity testing. Sediment toxicity testing would first be conducted using the subchronic (10

- d ) sediment toxicity test guidelines (OSCPP 850.175 and 850.1740). Pending a comparison of estimated environmental concentrations (EEC) in sediment and pore water with toxicity results from the 10

- d sediment toxicity studies, the need for one or more chroni c sediment toxicity studies would be determined.

### 39 OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data needed to conduct risk assessment? Justification and Assumptions EPA will Make in Absence of Data

Aquatic plant Toxicity Test using Lemna
spp. 46246102 Acceptable

850.4500 Algal toxicity 46246109 Acceptable

No 46246105 Acceptable

46246106 Acceptable

46246110 Acceptable

850.4550 Cyanobacteria 46246103 Acceptable No



### Table 1 6

. Prothioconazole

- Desthio: Submitted A quatic E cological E ffects D ata

OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data needed to conduct risk assessment? Justification and Assumptions EPA will Make in Absence of Data

850.1010 Acute toxicity for freshwater invertebrates No Data Yes This data is needed to fully characterize prothioconazole

desthio toxicity to freshwater invertebrates.

850.1025 850.1035 850.1045 850.1055 Acute toxicity for

e stuarine/marine

invertebrate s 46246017 Acceptable No

850.1075 Acute toxicity for f reshwater fish 46246020 Acceptable No 46246026 Acceptable

850.1075 Acute toxicity for estuarine/marine fish No Data Yes This data is needed to help understand toxicity to estuarine/marine fish

.

850.1300 Chronic toxicity with f reshwater invertebrate s 46246029 Acceptable No

Chironomid

Sediment Toxicity 47626901 Supplemental No

### 40 OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data needed to conduct risk assessment? Justification and Assumptions EPA will Make in Absence of Data

850.1350 Chronic toxicity estuarine/marine

inver tebrates 46246030 Acceptable No

850.1400 Fish Early Life Stage

- Fresh water fish No Data Yes These data are needed to address the potential toxicity of prothioconazole

- desthio to fresh water fish. It is r ecommended that test species be the most sensitive sp ecies indicated in the
acute freshwater fish toxicity test (850.1075; Rainbow trout

, Oncorhynchus mykiss ).

850.1400 Fish Early Life Stage

e stuarine/marine fish No Data No

Non

guideline Whole sediment chronic toxicity No Data No

850.1500 Fish life cycle

Fresh water fish 46246033 Supplemental No

850.1500 Fish life cycle

estuarine/marine fish No Data No

850.4500 Algal Toxicity Toxicity Test using Skeletonema

costatum No Data Yes These data are needed to understand the potential toxicity of prothioconazole

- desthio to

n on

- vascular estuarine/marine diatoms ( Skeletonema
costatum ).

850.4400 Aquatic plant Toxicity Test using Lemna spp. 46246104 Acceptable No

850.4500 Algal toxicity 46246108 Acceptable No

Non

Guideline Bioaccumulation and Biotransformation 46246035 Acceptable No

### 41 Table 17

. Prothioconazole

- S

- Methyl: Submitted A quatic E cological E ffects D ata

OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data needed to conduct risk assessment? Justification and Assumptions EPA will Make in Absence of Data

850.1010 Freshwater invertebrate acute toxicity 46246012 Acceptable No

850.1025 850.1035 850.1045 850.1055 Acute toxicity to estuarine and marine invertebrates No Data Yes These data are required given that the parent compound degrades into prothioconazole

- S

methyl in significant quantities in aquatic environments. These data will help to fully characterize the toxicity of prothioconazole

- S

methyl.

850.1075 Freshwater fish acute toxicity 46246021 Acceptable No

850.1075 A cute toxicity estuarine/marine fish No Data No

850.1300 Chronic toxicity freshwater invertebrate No Data No

850.1350 Aquatic invertebrate

lifecycle ( estuarine/marine ) No Data No

Non

guideline Whole sediment chronic toxicity No Data No

850.1400 Fish early life stage (fresh water) No Data No

850.4500 Algal toxicity 46246107 Supplemental No



### Table 1 8

. Prothioconazole: Submitted Terrestrial E cological E ffects D ata

OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data needed for risk assessment ? Justification and Assumptions EPA will Make in Absence of Data

850.2100 Avian oral toxicity 46246036 Acceptable

### 42 OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data needed for risk assessment ? Justification and Assumptions EPA will Make in Absence of Data

48024801 Acceptable Yes (passerine

species) Acute avian oral toxicity data are required for passerine species.

850.2200 Avian dietary toxicity 46246038 Acceptable No 46246040 Acceptable

850.2300 Avian reproduction 46246042 Acceptable No 46246044 Acceptable

870.1100 Mammal Acute Oral Toxicity 4624623 0 Acceptable No

870.1300 Acute inhalation
rat 46246246 Acceptable No

870.3800 2

- Generation Mammal Reproduction Toxicity 46246334 Acceptable No

850.3020 Honey bee adult
acute contact toxicity (Tier I) 46246046 Acceptable No 46246048 Acceptable Honey bee adult acute oral toxicity

(Tier I) (OECD Guideline 213) 46246046 Acceptable
No 46246048 Supplemental

Non

- Guideline Honey bee adult chronic oral toxicity (Tier I) No Data Yes These data are needed to fully characterize the toxicity to honey bees. A protocol should be submitted in advance of study initiation.

Special Study,

OECD 237 Honey bee larvae acute oral toxicity (Tier I) No Data Yes An acute oral toxicity study with honey bee larvae is needed.

Non

- guideline Honey bee larvae chronic toxicity (Tier I) No Data Yes A repeat dose toxicity study with honey bee larvae is needed.

Non

- guideline Field trial of residues in pollen and nectar

(Tier II) No Data Yes Based on the use pattern, a field trial measuring the residues of prothioconazole in pollen and nectar is needed.

Special Study,

OECD 75 Semi

- field testing for pollinators No Data Tiered Approach Results of the Tier I studies could trigger the higher Tier studies (Tier II and III), see above

.

### 43 OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data needed for risk assessment ? Justification and Assumptions EPA will Make in Absence of Data

850.3040 Field testing for pollinators No Data Tiered approach Results of the Tier I studies could trigger the higher Tier studies (Tier II and III), see abo ve

.

850.4100 S eedling E mergence and Seedling Growth, Tier 1 46246049 Acceptable No

S eedling E mergence and Seedling Growth, Tier 2 46246050 Acceptable No

850.4150 V egetative V igor

, Tier 1 46246049 Acceptable No

Vegetative Vigor, Tier 2 No Data NA No



### Table 1 9

. Prothioconazole

- Desthio: Submitted Terrestrial E cological E ffects D ata

OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data needed for risk assessment ? Current Additional Data Need

850.2100 Avian oral toxicity 46246037 Acceptable Yes (passerine

species) Acute avian oral toxicity data are required for passerine species.

850.2200 Avian dietary toxicity 46246039 Acceptable No

850.2300 Avian R eproduction 46246043 Acceptable No 46246045 Supplemental

870.1100 Mammal Acute oral

toxicity 46246231 Acceptable No

870.1300 Acute inhalation rat 46246247 Acceptable No

870.3800 2

- Generation Mammal Reproduction Toxicity 46246333 Acceptable No

### 44 OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data needed for risk assessment ? Current Additional Data Need

850.3020 Honey bee
acute contact toxicity No Data NA Yes These data are needed to fully characterize prothioconazole

- desthio toxicity to honey bees.

850.3020 Honey bee
acute oral

toxicity No Data NA Yes These data are needed to fully characterize prothioconazole

- desthio toxicity to honey bees.



### Data Gaps Prothioconazole Parent Compound

• OCSPP 850.1 735 : Whole sediment a cute t oxicity for f reshwater i nvertebrates (TGAI)

• OCSPP 850. 1740 : Whole sediment acute toxicity for estuarine/ marine invertebrates (TGAI)

• OCSPP 850.2100: Acute Oral Toxicity with passerine spe cies (TGAI)

• OECD TG 237 and Non

- guideline special studies: Honeybee larval acute and chronic oral toxicity studies (TGAI)

• Non

- Guideline: Honey bee adult chronic oral toxicity test (TGAI)

• Special study OECD TG 75 and OSCPP 850.3040: Semi

- field testing for pollinators (Tier II) and Field testing for pollinators (Tier III) (both studies that are conditionally required based on the results of the Tier I

– laboratory based studies listed above; if needed these additional field studies will be discussed pending the results of the acute and chronic adult and larval oral toxicity studies to honey bees and/or Tier II studies (for the full field study); ( TEP).

Prothioconazole

- Desthio

• OCSPP 850.1010: Acute toxicity for freshwater invertebrates

• OCSPP 850.1075:Acute toxicity for estuarine/ marine fish

• OCSPP 850.1400 Early life stage toxicity test with f reshwater fish

• OCSPP 850.4500 Algal Toxicity with Non

- vascular estuarine/marine diatom

• OCSPP 850.2100: Acute Oral Toxicity with avian passerine species

• OCSPP 850.3020: Honey Bee Acute Contact Toxicity

• OCSPP 850.3020 Honey Bee Acute Oral Toxicity

Prothioconazole

- S

- methyl

• OCSPP 850. 1025, 850.1035, 850.1045, 850.1055: Acute toxici ty to estuarine/marine invertebrates

Honeybee Toxicity
Although prothioconazole is categorized as practically non

- toxic to adult honeybees on an acute contact exposure basis, and by extension, to other beneficial terrestrial invertebrates on an acute exposure basis, there is considerable uncertainty regarding the potential effects of the compound on honeybee larval development and survival as well as potential for chronic effects. Therefore, additional data on pollinators is needed to fully characterize the risk associated wi th

### 45 prothio conazole use to all developmental stages of honeybees, as sensitivity may vary according to life

- stage and length of exposure (adult vs. larval and acute vs. chronic, respectively). Additional information is needed, but uncertainty associated wi th risks to honey bees need to be evaluated with more data to different life stages. Prothio conazole is systemic in plants so exposure via pollen and nectar is possible; and therefore, residues of pollen and nectar of crops are an additional data need. O pen literature data is needed to help better characterize some uncertainties regarding potential effects to bees and other non

- target terrestrial invertebrates. In addition, higher tier effects toxicity tests ( i.e., semi

- field and/or field studies

– Tier II and Tier III, respectively) may be needed, based on the results of the larval and chronic adult toxicity studies. Higher tier studies are recommended if the ratio of the EEC and larval or adult bee acute LD50> 0.4 or the ratio of the EEC and the chronic NOAEC> 1 . Incident data and/or compelling open literature studies can also be used to support the need for higher tier studies. Should the screening level risk assessment identify that there are risk concerns to bees, mitigation measures may need to be cons idered or the registrant may need to conduct Tier II or Tier III effects studies ( e.g. OECD Guideline 75 and/or 850.3040 guideline studies) that reduce unc ertainty by characterizing prothio conazole’s effects at the whole

- colony level 4



### .

4 http://www2.epa.gov/pollinator

- protection/pollinator

- risk

- assessment

- guidance

.

### 46 Study Title: Honey bee Adult Acute Oral Toxicity Rationale for Requiring the Data Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use settings. With eusocial bees, pesticide residues may be transferred to pollen and/or nectar of treated plants and subsequently brought back to the hive. Therefore, potential acute effects to adult honey bees and other insect pollinators from oral exposure to some pesticides could exist. Current ly available toxicity studies do not address possible effects of oral exposure on adult terrestrial insect survival. Because of the potential for pollen and nectar to be contaminated with pesticide residues, and subsequently brought back to the hive, it is important to determine the acute oral toxicity of this compound to adult honey bees and other insect pollinators.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for bees using the honey bee as a surrogate test species. The guidances discusses Tier 1 laboratory

- based acute oral toxicity studies of individual adult bees as a critical component of the screening

- level risk assessment process for examining potential adverse effects from specific routes of exposure. The guidance can be found at: http://www2.epa.gov/pollinator

- protection/pollinator

- risk

- assessment

- guidance

. Additional guidance on the honey bee oral toxicity te st design can be found in OECD Test Guideline 213 ( http://www.oecd

ilibrary.org/docserver/download /9721301e.pdf?expires=1423074617&id=id&accname=guest&checksum= 2F0764FCB4DCF01D32382952A2E995C3 ) Practical Utility of the Data How will the data be used? The Tier 1 acute oral toxicity d ata on adult honey bees serve as a foundation for the screening

- level assessment of potential risk non

- target organisms such as federally listed threatened or endangered and non

listed terrestrial invertebrate insects, including pollinators, from acute oral exposures to pesticid es. The data will be used to reduce uncertainties associated with the risk assessment for terrestrial invertebrates and will improve EPA’s understanding of the potential direct and indirect effects on a broad range of taxa. This study will also provide inf ormation with which to compare whether oral toxicity estimates differ from contact toxicity estimates obtained from other Tier 1 studies. If acute oral effects data for adult honey bees are not available, risks to terrestrial insects from acute oral exposu re will be assumed.

How could the data impact the Agency’s future decision

- making? The data will inform the determination required under FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse effec ts to non

- target species or is likely to adversely affect listed threatened or endangered species and/or modify their designated critical habitat. Without these data, EPA may need to presume risk

, which will limit the flexibility of pesticide products to c omply with FIFRA and the ESA, and could result in use restrictions.

### 47 Study Title: Honey bee Larvae Acute Oral Toxicity Rationale for Requiring the Data Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use settings. With eusocial bees, pesticide residues may be transferred to pollen and/or nectar of treated plants and subsequently brought back to the hive where develo ping larvae and pupae may be exposed. Therefore, potential adverse effects to developing bees could result from exposure to pesticide residues. Available toxicity studies do not address possible effects on brood (larvae and pupae) survival/development. B ecause of the potential for pollen and nectar to be contaminated with pesticide residues, and subsequently brought back to the hive, it is important to determine the acute toxicity of this compound to bee brood.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for bees using the honey bee as a surrogate test species. The guidances discusses Tier 1 laboratory

- based acute toxicity studies of individual honey bee larvae as a critical component of the screening

- level risk assessment process for examining potential risks from specific routes of exposure. The guidance be found at: http://www2.epa.gov/pollinator

- protection/pollinator

- risk

- assessment

- guidance . Additional guidance on larval honey bee toxicity test design can be found in OECD Test Gu ideline 237 ( http://www.oecd

ilibrary.org/docserver/download/9713171e.pdf?expires=1422485600&id=id &accname=guest&checksum= D8E07C2B1DF77BF096C3B29F55BF86A7 ). In some cases, information pertaining to acute toxicity to honey bee larvae may be obtained with the chronic honey bee larval test thereby negating the need for separate acute and chronic larval to xicity tests. Practical Utility of the Data How will the data be used? The Tier 1 acute toxicity d ata on honey bee larvae serve as a foundation for the screening

- level assessment of potential risk to non

- target organisms including federally listed threat ened or endangered and non

- listed terrestrial invertebrates , including pollinators, and/or modify their designated critical habitat from acute exposures to pesticides. The data will be used to reduce uncertainties associated with the risk assessment for terrestrial invertebrates and will improve EPA’s understanding of the potential effects on terrestrial species and whether there is a differential sensitivity of larval bees relative to adult bees. If acute effects data for larvae are not available, risks to terrestrial insects from acute exposure will be assumed

.
How could the data impact the Agency’s future decision

- making? The data will inform the determination required under FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse effects to non

- target species or is likely to adversely affect listed threatened or endan gered species and/or modify their designated critical habitat. Without these data, EPA may need to presume risk which will limit the flexibility of pesticide products to comply with FIFRA and the ESA, and could result in use restrictions.

### 48 Study Title: Honey Bee Adult Chronic Oral Toxicity Rationale for Requiring the Data Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use settings. With eusocial bees, p esticide residues may be transferred to pollen and/or nectar of treated plants and subsequently brought back to the hive. Therefore, potential chronic effects to adult honey bees and other pollinators from oral exposure to some pesticides could exist. Currently av ailable toxicity studies do not address possible lethal and sublethal effects of chronic oral exposure on adult terrestrial invertebrates and will assist in determining whether the sensitivity of adult bees differs from that of earlier life stages. Because of the potential for pollen and nectar to be contaminated with pesticide residues, and subsequently brought back to the hive, it is important to determine the chronic oral toxicity of this compound to adult honey bees and other pollinators.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for bees using the honey bee as a surrogate test species. The guidances discusses Tier 1 laboratory

- based chronic oral toxicity studies of individual adult honey bees as a criti cal component of the screening

- level risk assessment process for examining potential risks from specific routes of exposure. The guidance can be found at: http:/ /www2.epa.gov/pollinator

- protection/pollinator

- risk

- assessment

- guidance . Although study design elements for the chronic 10

- day oral toxicity test with honey bees are similar to the OECD TG 213 acute oral toxicity test ( http://www.oecd

ilibrary.org/docserver/download/9721301e.pdf?expires=1422484908&id=id&accname=guest& checksum= C38495D2A570AC2216CFB1F223D24AA7 ), EPA requires that the proposed protocol for this study be submitted for review and approval by EPA prior to initiating the test

. Practical Utility of the Data How will the data be used? The Tier 1 chronic toxic ity d ata on adult bees serve as a foundation for the screening

- level assessment of potential risk to non

- target organisms including federally listed threatened or endangered species and non

listed terrestrial invertebrates , including pollinators, from chro nic oral exposures to pesticides. The data will be used to reduce uncertainties associated with the risk assessment for terrestrial invertebrates and will improve EPA’s understanding of the potential direct and indirect lethal and sublethal effects on a br oad range of terrestrial species, particularly insect pollinators and to determine whether adult toxicity differs substantially from other life stages evaluated in other Tier 1 tests. If chronic oral effects data for adults are not available, risks to terr estrial insects from chronic exposure will be assumed.

How could the data impact the Agency’s future decision

- making? The data will inform the determination required under FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse effects to non

- target species or is likely to adversely affect listed threatened or endan gered species and/or their designated critical habitat. Without these data, EPA may need to presume risk which will limit the flexibility of pesticide products to comply with FIFRA and the ESA, and could result in use restrictions.

### 49 Study Title: Honey Be e Larvae Chronic Oral Toxicity Rationale for Requiring the Data Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use settings. For eusocial bees, pesticide residues may be transferred to pollen and/or nectar of treated plants and subsequently brought back to the hive where larvae and pupae may be exposed. Therefore, potential effects to developing bees could result from chronic exposure to pesticide residues. Available toxicity studies do not address possible chronic effects on brood (larvae and pupae) survival. Because of the po tential for pollen and nectar to be contaminated with pesticide residues, and subsequently brought back to the hive, it is important to determine chronic larval/pupal toxicity and whether adult emergence is adversely affected. This study will provide infor mation on whether honey bee larvae differ in sensitivity from adult bees following chronic exposure.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for bees using the honey bee as a surrogate test species. The guidances discusses Tier 1 laboratory

- based chronic toxicity studies of individual honey bee larvae as a critical component of the screening

- level risk assessment process for examining potential risks from specific routes of exposure. The guidance can be f ound at: http://www2.epa.gov/pollinator

- protection/pollinator

- risk

- assessment

- guidance

. Additional information on larval honey bee toxicity repeat exposure test d esign can be found in the OECD draft guidance ( http://www.oecd.org/env/ehs/testing/Draft_GD_honeybees_rep_exp_for_2nd_CR_25_November_2013.p df

). A lthough study design elements for the chronic 21

- day toxicity test with honey bee larvae have been drafted, EPA requires that the proposed protocol for this study be submitted for review and approval by EPA prior to initiating the test. Practical Utility of the Data How will the data be used? The Tier 1 chronic toxicity d ata on bee larvae serve as a foundation for the screening

- level assessment of potential risk to non

- target organisms including federally listed threatened or endangered and non

- listed terrestrial invertebrates, including insect pollinators, from chronic exposures to pesticides. These data will be used to reduce uncertainties associated with the risk assessment for terrestrial invertebrates and will improve EPA’s understanding of the pot ential direct and indirect lethal and sublethal effects on a broad range of terrestrial species, particularly insect pollinators. These data will also assist in determining whether early life stages of the bee differ in their sensitivity to pesticides rela tive to adults. If chronic effects data for larvae are not available, risks to terrestrial insects from chronic exposure will be assumed.

How could the data impact the Agency’s future decision

- making? The data will inform the determination required under FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse effects to non

- target species or is likely to adversely affect listed threatened or endangered species and/or modify their designated critical habitat. Without these data, EPA may need to presume risk which will limit the flexibility of pesticide products to comply with FIFRA and the ESA, and could result in use restrictions.

### 50 Study Title: Semi

- field Testing for Pollinators (tunnel or colony feeding studies) Rationale for Requiring the Data Tier 2 studies are conditional on the outcome of the screening

- level assessment where acute and/or chronic risk levels of concern have been exceeded for terrestrial invertebrates. Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use settings. For eusocial bees, pesticide residues may be transferred to pollen and/or nectar of treated plants and subsequently brought back to the hive and may adversely affect developing brood (egg, larvae, and pupae) and adult bees. Screening

- level (Tier 1) studies of individual bees do not address possible effects and/or exposure to pesticide residues at the colony

- level. Because of the potential for pollen and nectar to be co ntaminated with pesticide residues, and subsequently brought back to the hive, it is important to determine whether bee colonies may be negatively affected under relatively controlled exposure conditions of a semi

- field study. In addition to providing effe cts data, these studies can provide data on pesticide residues in pollen/nectar of treated plants.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for bees using the honey bee as a surrogate test species. This guidance describes the tiered testing process and can be found

at: http://www2.epa.gov/pollinator

- protection/pollinator

- risk

- assessment

- guidance , Additional info rmation

on honey bee colony studies under semi

- field conditions can be found in the OECD Guidance 75 ( http://www.oecd.org/officialdo cuments/publicdisplaydocumentpdf/?cote=env/jm/mono% 282007%2922& doclanguage=en ). Due to the complexities of this study, EPA requires that the proposed protocol for this study be submitted for review EPA prior to initiating the test. Practical Utility of t he Data How will the data be used? Tier 2 colony

- level data will be used to assess potential risk to non

- target organisms including listed and

non

- listed terrestrial social invertebrate species and to determine whether effects observed in the screening

level (Tier 1) laboratory

- based studie s of individual bees are evident in colony

- level studies under semi

- field conditions. The Tier2 semi

- field test of whole colonies is a relatively controlled study, i.e ., bees are confined to a specific area that is designed to represent potential field

- level exposure and account for hive dynamics, which are not achievable from other pollinator studies. This study will be used to determine whether adverse effects to inse ct pollinators at the whole colony level, may result for the use of pesticides and will help to refine risk estimates derived in the screening

- level risk assessment for beneficial terrestrial invertebrates. Measured residues in pollen/nectar can also be us ed to refine risk estimates derived from model

- based or default values in the screening

- level assessment.

How could the data impact the Agency’s future decision

- making? The data will inform the determination required under FIFRA or the ESA as to whether c ontinued registration of a pesticide is likely to result in unreasonable adverse effects to non

- target species or is likely to adversely affect federally listed threatened or endangered species or their designated critical habitat. Without these data, EPA may need to presume risk which will limit the flexibility of pesticide products to comply with FIFRA and the ESA, and could result in significant use restrictions.

### 51 Study Title: Semi

- field Testing for Pollinators (tunnel or colony feeding studies) Rationale for Requiring the Data For eusocial bees, pesticide residues may be transferred to pollen and/or nectar of treated plants and subsequently brought back to the hive and may adversely affect developing brood (egg, larvae, and pupae) and adult bees. Tier 2 feeding studies are conditional on the outcome of the screening

- level assessment where acute and/or chronic risk levels of concern have been exceeded for terrestrial invertebrates based on Tier 1 studies of individual bees. Feeding studies uti lize free foraging bee colonies that are “dosed” with specific quantities of test material and represent a means of ensuring exposure to the test material through spiked pollen and/or sugar solutions fed to the colony while still allowing the bees to forag e freely. Since bee colonies are not confined to enclosures, colonies can be exposed for longer duration periods without subjecting the bees to stress that typically results from Tier 2 tunnel studies. Available toxicity studies of individual bees (Tier 1) conducted to support screening

- level assessments do not address possible effects and/or exposure to pesticide residues at the colony

- level. It is therefore important to determine whether bee colonies may be negatively affected where bees are free foraging and have the option to collect/consume alternative forage items beyond the spiked food. Since multiple dose levels can be more readily tested, feeding studies can help to define dose

- response relationships at the whole colony level.

The Office of Pestic ide Programs has made available a guidance regarding ecological testing for bees using the honey bee as a surrogate. This guidance describes the tiered testing process and can be found at: http://www2.epa.gov/pollinator

- protection/pollinator

- risk

- assessment

- guidance

. Additional information on honey bee colony feeding studies can be found in the EPPO Guidance 170 ( www.nationalbeeunit.com/downloadDocument.cfm?id=191 )

. Although study design elements for the feeding study are available through the EPPO Guidance 170, EPA requires that the proposed protocol for this study be submitted for review and approval by EPA prior to initiating the test. Practical Utility of the Data How will the data be used? Tier 2 colony feeding data will be used to assess potential risk to non

- target organisms including listed and

non

- listed terrestrial social invertebrate species. The colony feeding study is designed to represent potential field

- level exposure and account for hive dynamics using longer duration exposure periods than are possible in Tier 2 tunnel studies. This study will be used to determine whether potential adverse effects to insect polli nators at the whole colony level when bees are able to forage naturally beyond the spiked food. Results from the feeding study will help to refine the screening

- level risk assessment for beneficial terrestrial invertebrates that were based on Tier 1 studie s on individual bees. Since feeding studies can help to define a dose

- response relationship at the colony level, the studies can provide a means of determining exposure thresholds below which the likelihood of adverse effects on colonies may be low.

How could the data impact the Agency’s future decision

- making? The Tier 2 colony

- level data will be used to refine screening

- level risk estimates derived using Tier 1 laboratory

- based data on individual bees. The Tier 2 data will help to inform the determinati on required under FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse effects to non

- target species or is likely to adversely affect federally listed threatened or endangered species or their des ignated critical habitat. Without these data, EPA may need to presume risk which will limit the flexibility of pesticide products to comply with FIFRA and the ESA, and could result in significant use restrictions.

### 52 Study Title: Field Testing for Pollinators Rationale for Requiring the Data Tier 3 studies are conditional on the outcome of the screening

- level assessment (Tier 1) where acute and/or chronic risk levels of concern have been exceeded for terrestrial invertebrates and where Tier 2 studies either under semi

- field tunnel conditions a nd/or feeding studies have indicated potential adverse effects at the colony level. Available toxicity studies from lower

- tier studies do not address possible effects and/or exposure to pesticide residues at the colony

- level under actual pesticide use cond itions and where specific uncertainties regarding the likelihood of exposure and/or effects remain. Full

- field studies also provide an opportunity to measure residues in pollen and nectar as well as various matrices (beebread, honey, wax) within the colony to obtain a more realistic understanding of exposure.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for bees using the honey bee as a surrogate. This guidance describes the tiered testing process and can be f ound at: http://www2.epa.gov/pollinator

- protection/pollinator

- risk

- assessment

- guidance

. Additional information on honey bee colony studies under full

- field conditions can be found in the OCSPP 850.3040 ( http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0154

- 0018 ). Useful guidance is also available throug h OCSPP 850.2500 (Field Testing of Terrestrial Wildlife; http://www.epa.gov/ocspp/pubs/frs/publications/Test_Guidelines/series850.htm ) Although design elements fo r the full

- field colony

- level study are available through the 850.3040 and 850.2500, EPA requires that the proposed protocol for this study be submitted for review and approval by EPA prior to initiating the test; the protocol should attempt to address spe cific uncertainties identified in lower

- tier studies. Practical Utility of the Data How will the data be used? Tier 3 colony

- level data will be used to further characterize potential risk to non

- target organisms including listed and non

- listed terrestrial social invertebrate species and to refine screening

- level risk estimates that were based on individual bee resp onses. The semi

- field test is a controlled study that is designed to represent potential field

- level exposure under relatively controlled conditions and account for hive dynamics, which are not achievable from lower

- tier pollinator studies. This study will be used to determine whether adverse effects to insect pollinators at the whole colony level, may result for the use of pesticides and will help to refine the screening

- level risk estimates for beneficial terrestrial invertebrates. This study will also be used to determine whether more refined (Tier 3) studies are needed to characterize risk.

How could the data impact the Agency’s future decision

- making? The data will inform the determination required under FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse effects to non

- target species or is likely to adversely affect federally listed threatene d or endangered species or their designated critical habitat. Without these data, EPA may need to presume risk which will limit the flexibility of pesticide products to comply with FIFRA and the ESA, and could result in significant use restrictions.

### 53 S tudy Title: Residues in Pollen and Nectar Rationale for Requiring the Data Terrestrial invertebrates are likely to be impacted if exposed to pesticides residues in various use settings. Pesticide residues may be transferred to pollen and/or nectar of treated plants and subsequently brought back to hive all life stages may be exposed. For some pesticides, the quantification of pollinator

- relevant residues in treated flowering plants is needed, since pollinators will be exposed to residues from either cu rrent or prior season applications (due to the potential for residues to accumulate in plants and trees). Residues in edible/transportable

- to

- hive parts of treated trees and plants, including (where appropriate), but not limited to, guttation water, sap/re sins, whole plant tissue ( e.g., leaves, stems), as well as blooming, pollen

- shedding, and nectar producing parts ( i.e. , flowers and, if present, extra

- floral nectaries) of plants may inform the potential for risk. Studies should be designed to provide resi due data for crops and application methods of

concern.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for bees using the honey bee as a surrogate. This can be found at: http://www2.epa.gov/pollinator

- protection/pollinator

risk

- assessment

- guidance

. Since residue studies are intended to provide exposure data in multiple matrices and under specific application conditions, EPA requires that the protocol is submitted for review and approval by EPA prior to initiation of the study. Practical Utility of the Data How will the data be used? Measured residue d ata will be used to refine cons ervative estimates of pesticide exposure and reduce uncertainties associated with the Tier 1 exposure assessment by providing direct measurements of pesticide concentrations resulting from actual use settings. Measured residues may provide a more realistic understanding of exposure through contact or ingestion with which to calculate risk quotients for individual bees as well as to characterize exposure to the colony. If measured residue data are not available, risk estimates for terrestrial insects will be based on model generated or default values used to support the screening

- level assessment.

How could the data impact the Agency’s future decision

- making? The data will inform the determination required under FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse effects to non

- target species or is likely to adversely affect federally listed threatene d or endangered species or their designated critical habitat. Without these data, EPA will have to rely on conservative estimates of exposure which may limit the flexibility of pesticide products to comply with FIFRA and the ESA, and could result in use re strictions.

### 54 Guideline Number: None (Agency

- Wide Guidelines found in USEPA 2000 and 2001) Study Title: Whole sediment: Chronic invertebrates freshwater & estuarine/marine Rationale for Requiring the Data No acceptable chronic sediment toxicity tests for freshwater or marine invertebrates have been submitted to satisfy the Agency’s updated data requirements for outdoor uses in 40 CFR Part 158 (October 26, 2007). Benthic organisms may be exposed to run

- off or spray drift from applications used in terrestrial e nvironments, based on the fate properties of prothioconazole and its degradates. The following lines of evidence suggest the potential for ecologically significant exposure of benthic

dwelling organism s to prothioconazole

. Prothioconazole has the potential to partition to the sediment (log Kow of 4.16 ), and remain for an extended amount of time (aerobic soil metabolism half

- life is up to 1936 days an d aerobic aquatic metabolism of up to 433 days). For freshwater sediment testing, tests on an amphipod ( e.g., Hyalella azteca) and a midge (e.g., Chironomus dilutus) are requested. Both freshwater species, Hyalella and Chironomus differ substantially in their ecological niche ( i.e., epibenthic vs. infaunal species), life history and phylogeny. For estuarine/marine sediment testing, tests on one amphipod species is requested ( e.g., Leptocheirus plumulosus ).

In some situations, a tiered testing strategy may be considered for requesting chronic sediment toxicity testing. In this approach, sediment toxicity testing would first be conducted with the aforementioned species using the subchronic (10

- d) sediment toxicity test guidelines (OSCPP 850.1735 and 850.1740). Then, pending a comparison of estimated en vironmental concentrations (EEC) in sediment and pore water with toxicity results from the 10

- d sediment toxicity studies, the need for one or more chronic sediment toxicity studies would be determined. This tiered testing approach has the potential advan tage of reducing the number of chronic (life cycle) studies that would be needed when results of the 10

- d (subchronic) tests in conjunction with sediment EECs indicate chronic testing is not likely to alter risk assessment conclusions. In some cases, howe ver, this tiered testing approach may result in the conduct of both a 10

- d (subchronic) and a chronic (life cycle) study. Practical Utility of the Data How will the data be used? Data from sediment toxicity studies will be used to estimate potential ris ks to benthic organisms associated with uses of prothioconazole . The data will reduce uncertainties associated with the current risk assessment for benthic species and will improve our understanding of the potential effects of prothioconazole on aquatic e cosystems.

How could the data impact the Agency’s future decision

- making? If the data indicates that registered prothioconazole uses may pose a risk of adverse effects to non

- target benthic organisms above the Agency Level of Concern, the Agency may explore decision options to mitigate this risk. T he lack of these data will limit the flexibility the Agency and registrants have in coming into compliance with the Endangered Species Act, and could result in use restrictions for prothioconazole which may otherwise be avoided, or which are unnecessarily severe.

Currently, the 850 guidelines for chronic sediment toxicity testing are b eing finalized. However, Agency

wide guidelines are available for chronic testing of freshwater 5 

### and estuarine/marine organisms 6



### . Therefore, as indicated in 40 CFR Part 158, the registrant is required to submit a protocol for approval prior to initiating the study until such time as the OCSPP 850 chronic sediment testing guidelines are published.

5 USEPA 2000. Methods for Measuring the Toxicity and Bioaccumulation of Sediment

- associated Contaminants with Freshwater Invertebrates. EPA 600/R

- 99/064. March.

6 USEPA 2001. Methods for Assessing the Chronic Toxicity of Marine and Estuarine Sediment

- assoc iated Contaminants with the Amphipod Leptocheirus plumulosus. EPA 600/R

- 01/020. March.

### 55 

# 12. References

Food and Agriculture Organization of the United Nations. 2000. FAO PESTICIDE DISPOSAL SERIES 8. Assessing Soil Contamination: A Reference Manual. Appendix 2. Parameters of pesticides that influence processes in the soil. Editorial Group, FAO Information Division: Rome. http://www.fao.org/DOCREP/003/X2570E/X2570E00.htm

Jones, R.D. et al., 2000. Guidance for use of the Index Reservoir and Percent Crop Area Factor in Drinking Water Assessments (March 21, 2000). Office of Pesticide Programs, Environ mental Fate and Effects Division, U.S. Environmental Protection Agency. Arlington, VA.

USEPA. 1999. Guidance for Use of the Index Reservoir in Drinking Water Exposure Assessments. Arlington, VA.

USEPA. 2000. Drinking Water Screening Level Assessment. Part A: Applying a Percent Crop Area Adjustment to Tier II Surface Water Model Estimates for Pesticide Drinking Water Exposure Assessments. FQPA Science Policy Document .Public Comment Draft September 1, 2000. Federal Register: October 11, 2000 (volume 65 , number 197). Electronic copy available at http://www.epa.gov/pesticides/trac/science/ .

USEPA. 2002a. Guidance for Selecting Input Parameters in Modeling the Environmental Fate and Transport of Pesticides, Version II (February 28, 2002). Office of Pe sticide Programs, Environmental Fate and Effects Division, U.S. Environmental Protection Agency. Arlington, VA.

U.S. EPA. 2002b. Pesticide Root Zone Model (PRZM) Field and Orchard Crop Scenarios: Standard Procedures for Conducting Quality Control and Qual ity Assurance. Office of Pesticide Programs, Environmental Fate and Effects Division, U.S. Environmental Protection Agency. Arlington, VA.

U.S. EPA. 2003b. Use of Regional Percent Crop Area Factors in Refined Drinking Water Assessments. US EPA Office of Pesticide Programs (OPP), Environmental Fate and Effects Division (EFED), Water Quality Technical Team (WQTT). Arlington, VA

USEPA, 2003c. SCI

- GROW 2.3: Windows Version of SCI

- GROW. September 30, 2003. Office of Pesticide Programs, Environmental Fate and Effects Division, U.S. Environmental Protection Agency. Arlington, VA.

USEPA. 2004. Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs . United States Environmental Protection Agency (USEPA). Environmental Fate and Effe cts Division. Office of Pesticide Programs. Available at http://www.epa.gov/espp/consultation/ecorisk

- overview.pdf

.

### 56 USEPA. 2006 a . 1,2,4

- Triazole, Triazole Alanine, Triazole Acetic Acid: Drinking Water Assessment in Support of Reregistration and Registrat ion Actions for Triazole

- derivative Fungicide Compounds. Office of Pesticide Programs Environmental Fate and Effects Division. DP Barcode 320682, dated February 28, 2006.

USEPA. 2006 b . 1,2,4

- Triazole, Triazole Alanine, Triazole Acetic Acid: Human Health A ggregate Risk Assessment in Support of Reregistration and Registration Actions for Triazole

derivative Fungicide Compounds. Office of Pesticide Programs Health Effects Division and Environmental Fate and Effects Division. DP Barcode 322215, dated February 7, 2006.

U.S. EPA. 2006 c

. Prothioconazole Tier II Estimated Drinking Water Concentrations (EDWCs) for Use in the Human Health Risk Assessment. [Second Revision] . DP Barcode: 320265. Office of Pesticide Programs, Environmental Fate and Effects Division. June 2006.

U.S. EPA. 2006 d . Environmental Fate and Ecological Risk Assessment for the Registration of Prothioconazole (DP Barcode: 324660). Office of Pesticide Programs, Environmental Fate and Effects Division. June 2006.

U.S. EPA 2008. Ecological Risk Assessment for the Prothioconazole Section 3 New Use on Soybeans and Sugar Beets. DP Barcode: 329925/337791. Office of Pesticide Programs, Environmental Fate and Effects Division. January 2008.

U.S. EPA. 2009 a

. Drinking Water Assessment in Support o f the New Use of Prothioconazole on Crop Groups 15 and 16 (Cereal Grains and Forage, Fodder and Straw of the Cereal Grains Group Except Sweet Corn, Sorghum and Rice) and Sweet Corn (DP Barcode: 369343). Office of Pesticide Programs, Environmental Fate and Effects Division. December 2009.

USEPA. 2009 b

. ECOTOXicology Database

, United States Environmental Protection Agency (USEPA)

. Available at http://cfpub.epa.gov/ecotox/ (Accessed March 27, 2015).

U.S. EPA. 2010 a

. Drinking Water Assessment in Support of the New Use of Prothioconazole on Nursery Seed and Seedlings of Conifers and Hardwoods; Foliar Use on Rice and Rice Hulls; and Seed Treatment Use on Dried Shelled Pea and Bean Subgroup 6C (Except Soybean), R ice and Soybean” ( DP Barcodes: D373683, D378621, D378998) . Office of Pesticide Programs, Environmental Fate and Effects Division. October 2010.

U.S. EPA 2010 b . Ecological Risk Assessment in Support of the Prothioconazole Section 3 New Uses on Alfalfa Se ed, Dry Bean and Pea Seeds (Crop Group 6C), Soybean Seed, Potato Seed Pieces, Cereal Grain Seeds, Rice Seed, Nursery Seed, and New Foliar Uses on Rice, Nursery Seedlings of Conifers and Hardwoods and an Amendment to the Use on Corn. DP Barcodes: 378999, 37 3681, 378623, 381890. Office of Pesticide Programs, Environmental Fate and Effects Division. December 2010.

U.S. EPA. 2012 a

. Drinking Water Assessment in Support of the Proposed Prothioconazole Section 3 Seed Treatment Uses on Seeds of Cereal Grains Cr op Groups 15 & 16 (Except

### 57 Sorghum and Rice ( DP Barcode 398128). Office of Pesticide Programs, Environmental Fate and Effects Division. February 2012.

U.S. EPA 2012 b . Environmental Fate and Ecological Risk Assessment for the Proposed New Uses of Prothioc onazole as a Seed Treatment at an Increased Rate on Cereal Grains of Crop Groups 15 & 16, as a Seed Treatment on Corn (Field, Sweet, Pop), and as a Foliar Treatment on Soybean at an Increased Rate. DP Barcodes: D395296, 399435. Office of Pesticide Programs , Environmental Fate and Effects Division. May 23, 2012.

U.S. EPA. 2012 c

. Drinking Water Assessment in Support of the Proposed Prothioconazole Section 3 New Uses on Bushberry (Crop Subgroup 13

- 07B), Low Growing Berry Subgroup, Except Strawberry (Crop Su bgroup 13

- 07H) and Cucurbit Vegetables (Crop Group 9). ( DP Barcode: D405409 ) 

### . Office of Pesticide Programs, Environmental Fate and E ffects Division. November 2012

.

USEPA. 2014 a

. Toxicity Testing and Ecological Risk Assessment Guidance for Benthic Invertebrates

. United States Environmental Protection Agency (USEPA). Environmental Fate and Effects Division. Office of Pesticide Programs. March 11, 2014.

USEPA. 201 4 b

. Guidance for Addressing Unextracted Residues in Laboratory Studies. United States Environmental Protection Agency (USEPA). Environmental Fate and Effects Division. Office of Pesticide Programs. September 12, 2014.

USEPA. 2015 a

. Screening Level Estimates of Agricultural Uses of Prothioconazole (113961). United States Environmental Pro tection Agency (USEPA). Biological and Economic Analysis Division. Office of Pesticide Programs. May 11, 2015.

USEPA. 2015 b . BEAD Chemical Profile (BCP) for Registration Review : Prothioconazole (113961). United States Environmental Protection Agency (USE PA). Biological and Economic Analysis Division. Office of Pesticide Programs. September, 2015.

### 58 APPENDIX A. Environmental Fate Studies

161

- 1 Hydrolysis

MRID Citation Reference

46246505 2050563 Riegner, K. (1998) Hydrolysis of [Phenyl

- UL

- (Carbon

- 14)]JAU6476 in Sterile Aqueous Buffer Solutions. Project Number: M/1110902/4, MR/623/98, 4412. Unpublished study prepared by Bayer AG Institute of Metabolism Research and Residue Analysis. 41 p.

46246506 2050564 Hellpointner, E. (199 3) SXX 0655: Hydrolysis in Buffers. Project Number: M/1110379/2, PF/3882. Unpublished study prepared by Bayer AG Institute of Metabolism Research and Residue Analysis. 39 p.



### 161

- 2 Photodegradation

- water

MRID Citation Reference

46246507 2050565 Gilges, M.; Bornatsch, W. (2001) Photolysis of JAU6476 in Sterile Aqueous Buffer. Project Number: M/1120917/1, MR/213/01. Unpublished study prepared by Bayer Ag Institute of Metabolism Research and Residue Analysis. 71 p.

46246508 DER not located 2053922 Ref Hellpointner, E. (2001) Determination of the Quantum Yield and Assessment of the Environmental Half

- life of the Direct Photodegradation in Water of JAU6476. Project Number: M/1430957/9, MR/101/01, 214. Unpublished study prepared by Bayer Ag Ins titute of Metabolism Research and Residue Analysis. 39 p.

46246509 DER not located 2053922 Ref Hellpointner, E. (1990) Determination of the Quantum Yield and Assessment of the Environmental Half

- life of the Direct Photodegradation of SXX 0665 in Water. Pr oject Number: M/1120358/0, PF3852, ME/24/93. Unpublished study prepared by Bayer Ag Institute of Metabolism Research and Residue Analysis. 32 p.



### 161

- 3 Photodegradation

- soil

MRID Citation Reference

46246510 2050566 Gilges, M. (2001) Photolysis of JAU6476 on Soil Surface. Project Number: M/1130918/3, MR/242/00. Unpublished study prepared by Bayer Ag Institute of Metabolism Research and Residue Analysis. 47 p.

46359101 DER not located 2050571

- ref Gilges, M. (2001) Photolysis of JAU6476 on Soil Surface. Project Number: M/1130918/3, MR/242/00. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 54 p.



### 162

- 1 Aerobic soil metabolism

MRID Citation Reference

### 59 46246511 2050567 Hellpointner, E. (2001) Proazolthion (Proposed) [JAU6476]: Degradation and Metabolism of JAU6476 in Aerobic Soils. Project Number: M/1250893/8, MR/104/01, 215. Unpublished study prepared by Bayer Ag Institute of Metabolism Research and Residue Analysis. 101 p.

46246512 2050568 Gilges, M. (2000) Aerobic Degradation of JAU6476 in Two Soils. Project Number: M/1250960/3, MR/549/99. Unpublished study prepared by Bayer Ag Institute of Metabolism Research and Residue Analysis. 59 p.

46246513 2050569 Gilges, M. (2001) Degradation of JA U6476

- desthio (SXX0665) in Four Soils Under Aerobic Conditions. Project Number: M/1251001/0, MR/327/00. Unpublished study prepared by Bayer Ag Institute of Metabolism Research and Residue Analysis. 58 p.

46246514 2050570 Gilges, M. (2001) Degradation of J AU6476

- S

- methyl (WAK7861) in Four Soils Under Aerobic Condition. Project Number: M/1251002/1, MR/340/00. Unpublished study prepared by Bayer Ag Institute of Metabolism Research and Residue Analysis. 55 p.

46359102 DER not located Gilges, M. (2000) Aerobic Degradation of JAU6476 in Two Soils. Project Number: M/1250960/3, MR/549/99. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 68 p.

46449246 2050568 Gilges, M. (2000) Aerobic Degradation of JAU6476 in Two Soils. Project Number: M /1250960/3, MR/549/99. Unpublished study prepared by Bayer Ag Institute of Metabolism Research and Residue Analysis. 59 p.



### 162

- 3 Anaerobic aquatic metabolism

46246516 2050571 Scholz, K. (2001) Anaerobic Aquatic Metabolism of JAU6476. Project Number: M/1520919/7, MR/275/01. Unpublished study prepared by Bayer AG Institute of Metabolism Research and Residue Analysis. 76 p.



### 162

- 4 Aerobic aquatic metabolism

46246515 2050572 Brumhard, B.; Oi, M. (2001) Aerobic Degradation and Metabolism of the Ac tive Ingredient JAU6476 in the Water/Sediment System. Project Number: M151/0899/3, MR/395/01, BBJ51. Unpublished study prepared by Bayer Ag Institute for Metabolism Research and Residue Analysis. 95 p.

48441901 DER not located Kitschmann, P. (1997) Degradation and Metabolism of [Trifluoromethyl

- Phenyl

- (U)

- (Carbon 14)] Labeled CGA 279202 in Two Aquatic Systems. Project Number: MO/01/001631, 95PK03. Unpublished study prepared by Novartis Crop Protection, AG. 149 p.

48441902 DER not located Ulbrich, R. (1997) Degradation and Metabolism of (U)

- (Carbon 14)

- Phenyl

Glyoxylat

- Labeled CGA 279202 in Two Aquatic Systems. Project Number: 95UL02, MO/01/001628. Unpublished study prepared by Novartis Crop Protection, AG. 132 p.



### 163

- 1 Leach/adsorp/desorption

MRID Citation Reference

### 60 46246449 DER not located 2053922 Ref Sommer, H. (2001) Estimation of the Absorption Coefficient (Koc) of JAU6476 on Soil Using High Performance Liquid Chromatography (HPLC). Project Number: M/138/1079/9, MR/473/00. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 37 p.

46246450 2050575 Fent, G. (1998) Adsorption/Desorption of (phenyl

- UL

- (Carbon 14))SXX0665 on Four Different Soils. Project Number: BAY28, FM768. Unpublished study prepared by Staatliche Lehr

- und Forschungsanstalt fuer. 46 p.

46246501 2050576 Hein, W. (1999) Adsorption/Desorption of S

- methyl

- JAU6476 on Four Different Soils. Project Number: BAY30, FM/774. Unpublished study prepared by Staatliche Lehr

- und Forschungsanstalt fuer Landwirt, Weinbau, Gartenbau. 42 p.

46246502 DER not located referenced in 2053922 Sommer, H. (2001) Estimation of the Adsorption Coefficient (Koc) of JAU6476

- thiazocine on Soil Using High Performance Liquid Chromatography (HPLC). Project Number: M/13811 09/3, MR/265/01. Unpublished study prepared by Bayer Ag Institute of Metabolism Research and Residue Analysis. 34 p.

46246503 DER not located Riegner, K. (1999) Leaching Behavior of JAU6476 Formulated as 250 EC in Soil (Parent Leaching). Project Number: M /1320961/2, MR/098/99, 4430. Unpublished study prepared by Bayer AG Institute of Metabolism Research and Residue Analysis. 39 p.

46246504 2050573 Babczinski, P. (2001) Aged Soil Column Leaching of JAU6476. Project Number: M/1211074/6, MR/364/00. Unpublish ed study prepared by Bayer AG Institute of Metabolism Research and Residue Analysis. 90 p.

46246534 DER not located 2053922

- ref Sabbagh, G.; Arthur, E. (2004) Soil Adsorption Value (Koc) for JAU 6476. Project Number: 200817. Unpublished study prepared by Bayer Corp. 19 p.

46246539 2050574 Riegner, K. (1999) Leaching Behaviour of JAU 6476 Formulated as 250 EC in Soil (Parent Leaching). Project Number: M/132/0961/2, 109139. Unpublished study prepared by Bayer Ag Institute for Metabolism Research and Residue Analysis. 40 p.



### 164

- 1 Terrestrial field dissipation

MRID Citation Reference

46246517 2050577 Wood, S. (2004) Terrestrial Field Dissipation of JAU6476 in California Soil, 1999. Project Number: J6022102, 200051, F99534/001. Unpublished study prepared by Bayer Corp. and A & L Great Lakes Laboratories. 124 p.

46246518 2050578 Wood, S. (2004) Terrestrial Field Dissipation of JAU6476 in Georgia Soil, 1999. Project Number: J6022101, 110799, F99540/001. Unpublished study prepared by Bayer Corp., Bayer Research Farm and A & L Great Lakes Laboratories. 135 p.

46246519 2050579 Wood, S. (2004) Terrestrial Field Dissipation of JAU6476 in New York Soil, 1999. Project Number: J6022103, 200053, F99557/001. Unpublished study prepared by Bayer Corp., A.C.D .S. Research, Inc. and A & L Great Lakes Laboratories. 134 p.

### 61 46246520 DER not located 2053922 Ref Lenz, M. (2004) Terrestrial Field Dissipation of JAU6476 in Saskatchewan Soil, 1999. Project Number: J6022105, 200134, F99573/001. Unpublished study prepare d by Bayer Corp., A & L Great Lakes Laboratories and AgQuest. 137 p.

46246521 DER not located 2053922 Ref Lenz, M. (2004) Terrestrial Field Dissipation of JAU6476 in Manitoba Soil, 1999. Project Number: J6022106, 200096, F99560/001. Unpublished study prep ared by Bayer Corp., A & L Great Lakes Laboratories and AgQuest. 137 p.

46246525 DER not located 2053922 Ref Schramel, O. (2001) Determination of the Storage Stability of JAU6476 and the Metabolites JAU6476

- desthio and JAU6476

- S

- methyl in Soil. Project Number: P64190027, MR/644/99. Unpublished study prepared by Bayer Ag Institute of Metabolism Research and Residue Analysis. 52 p.

46246526 DER not located 2053922 Schramel, O. (2001) Dissipation of JAU 6476 (250 EC) in Soil Under Field Conditions (France, Germany, Great Britain, Italy). Project Number: RA/2152/98, R812587, R812595. Unpublished study prepared by Bayer Ag Institute of Metabolism Research and Residue Analysis. 151 p.



### 164

- 2 Aquatic field dissipation

MRID Citation Reference

46246522 2050580 Wyatt, D. (2004) Aquatic Field Dissipation of JAU6476 in a California Rice Field, 2000. Project Number: J6022401, 200060, F00519/001. Unpublished study prepared by Bayer Corp., Agricultural Advisors, Inc. and A & L Great Lakes Laboratories . 181 p.

46246523 2050581 Wyatt, D. (2004) Aquatic Field Dissipation of JAU6476 in an Arkansas Rice Field, 2000. Project Number: J6022402, 200067, F00520/001. Unpublished study prepared by Bayer Corp., Shoffner Farm Research and A & L Great Lakes Laboratories. 185 p.

46246524 2050582 Wyatt, D. (2004) Aquatic Field Dissipation of JAU6476 in a Cropped Arkansas Rice Field, 2000. Project Number: J6022403, 200078, F00520/001. Unpublished study prepared by Bayer Corp., Shoffner Farm Research, Battelle a nd A & L Great Lakes Laboratories. 148 p.



### 165

- 4 Fish accumulation bioconcentration/biotransformation

46246034 2050583 Dorgerloh, M.; Weber, E. (2001) (Carbon 14)

- JAU6476

- Bioconcentration and Biotransformation in Bluegill (Lepomis macrochirus) Under Flow

- Through Conditions. Project Number: E/2442023/7, DOM/21003. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 168 p

46246035 2050584 Dorgerloh, M.; Weber, E.; Spiegel, K. (2001) (Carbon 14)

- JAU6476

- Desthio

- Bioconcentration a nd Biotransformation in Bluegill (Lepomis macrochirus) Under Flow

- Through Conditions. Project Number: E/2441731/2, DOM/20006. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 131 p.

### 62 Appendix B. Ecological Effects Studies

71

- 1 Avian Single Dose Oral Toxicity
MRID Citation Reference

46246036 2051002 2050895

- memo Barkfknecht, R. (1999) JAU6476 techn. ai.: Acute Oral Toxicity for Bobwhite Quail (Colinus virginianus). Project Number: 2921561/6, BAR/LD028. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 35 p.

46246037 Desthio metabolite 2051001 2050895

- memo Grau, R. (1990) SXX 0665 (Technical Grade): Acute Oral LD50 to Bobwhite Quail. Project Number: E/2920414/2, VB/009. Unpublishe d study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 36 p.

48024801 2086131 2086130 Fredricks, T.; Christ, M. (2010) Toxicity of JAU 6476 Technical (Prothioconazole) During an Acute Oral LD50 with the Canary (Serinus canaria). Project Number: M/364387/01/1, EBJAL065, M/364387/01/1/OCR. Unpublished study prepared by Bayer CropScience. 35 p.



### 71

- 2 Avian Dietary Toxicity

MRID Citation Reference

46246038 2051000 2050895

- memo Barfknecht, R. (2001) JAU6476 techn.: 5

- Day

- Dietary LC50 for Bobwhite Quail (Colinus virginianus). Project Number: E/2951563/1, BAR/LC005. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 32 p.

46246039 Desthio metabolite 2050904 2050895

- memo Barfknecht, R. (2001) JAU6476

- D esthio .: 5

- Day

- Dietary LC50 for Bobwhite Quail (Colinus virginianus). Project Number: E/2951564/2, BAR/LC011. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 34 p.

46246040 2050919 2050895

- memo Barfknecht, R. (2001) JAU6476 techn.: 5

- Day

- Dietary LC50 to Mallard Duck (Anas platyrhynchos). Project Number: E/2971562/2, BAR/LC010. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 31 p.



### 71

- 4 Avian Reproduction

MRID Citation Reference

46246042 2050918 2050895

- memo Frieling, W. (2000) Reproduction Study in Bobwhite Quail with JAU 6476 (by Dietary Admixture). Project Number: 259842, 88353, 259842/MO/00/010540. Unpublished study prepared by Notox B.V. 231 p.

46246043 Desthio metabolite 2050917 2050895

- memo Barfknecht, R. (2002) JAU6476

- Desthio techn. ai.: Effects of a Subchronic Dietary Exposure to the Northern Bobwhite Quail Including Effects on Reproduction and Behavior. Project Number: E/2981830/1, BAR/REP006. Unpublished study prepar ed by Bayer Ag Institut fuer Ruckstands

- Analytik. 106 p.

### 63 46246044 2050916 2050895

- memo Frieling, W. (2000) Reproduction Study in Mallard Duck with JAU 6476 (by Dietary Admixture). Project Number: 259919, 88353. Unpublished study prepared by Notox B.V. 207 p.

46246045 Desthio metabolite 2050915 2050895

- memo Frey, L.; Martin, K.; Beavers, J.; et al. (2001) Desthio JAU

- 6476: A Reproduction Study with the Mallard (Anas platyrhynchos). Project Number: 149/181, 110617, J6740801. Unpublished study prepared by Wi ldlife International, Ltd. 200 p.



### 72

- 1 Acute Toxicity to Freshwater Fish

MRID Citation Reference

46246018 2051018 2050895

- memo Dorgerloh, M. (1999) JAU6476

- Acute Toxicity (96 hours) to Rainbow Trout (Oncorhynchus mykiss) in a Static Test. Project Number: E/2501657/6, DOM/99076. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

Analytik. 51 p.

46246019 2051019 2050895

- memo Kern, M.; Lam, C. (2003) Acute Toxicity of JAU 6476 480 SC to the Rainbow Trout (Oncorhynchus myki ss) Under Static Conditions. Project Number: EBJAX073, J6812201, 200193. Unpublished study prepared by Bayer Corp. 33 p.

46246020 Desthio metabolite 2050914 2050895

- memo Grau, R. (1990) SXX 0665 techn.: Acute Toxicity to the Rainbow Trout in a Static Test. Project Number: E/2800441/9, FF/298. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 28 p. Prothioconazole

- Desthio

46246021 2051020 2050895

- memo Dorgerloh, M.; Sommer, H. (2001) JAU6476

- S

- Methyl

- Acute Toxicity (96 hou rs) to Rainbow Trout (Oncorhynchus mykiss) in a Semi

- Static Test. Project Number: E/2802052/9, DOM/21047, 00699. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 47 p.

46246022 2051021 2050895

- memo Dorgerloh, M. (1999) JAU6476

- Acute Toxicity (96 Hours) to Bluegill (Lepomis macrochirus) in a Static Test. Project Number: E/2521695/0, DOM/99090, 00586. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

Analytik. 48 p.

46246023 2051012 2050895

- memo Kern, M.; Lam, C. ( 2003) Acute Toxicity of JAU 6476 480 SC to the Bluegill (Lepomis macrochirus) Under Static

- Renewal Conditions. Project Number: 200599, EBJAX075, J6810301. Unpublished study prepared by Bayer Corp. 34 p.

46246024 2051011 2050895

- memo Grau, R. (1991) SXX 06 65: Acute Toxicity to Golden Orfe in a Static Test. Project Number: E/2820400/6, FO/1253. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 29 p. Prothioconazole

- Desthio

46246025 2051010 2050895

- memo Dorgerloh, M. (2000) JAU6476

- Acute Toxicity (96 hours) to Common Carp (Cyprinus carpio) in a Static Test. Project Number: E/2861781/3, DOM/20010. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 40 p.

46246026 2051009 2050895

- memo Kern, M.; Lam, C. (2003) Acute Toxicity of JAU 6476

- Desthio to the Fathead Minnow (Pimephales promelas) Under Static

- Renewal Conditions. Project Number: EBJAZ071, J6811202, 200151. Unpublished study prepared by Bayer Corp. 35 p. Prothioconazole

- Desthio

### 64 72

- 2 Acute Toxicity to Freshwater Invertebrates

MRID Citation Reference

46246009 2051013 2050895

- memo Heimbach, F. (2001) Acute Toxicity of JAU6476 (tech.) to Water Fleas (Daphnia magna). Project Number: E/3201675/4, HBF/DM212. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 50 p.

46246010 2051014 2050895

- memo Kern, M.; Lam, C. (2003) Acute Toxicity of JAU 6476 480 SC Formulation to the Waterflea (Daphnia magna) Under Static

- Renewal Conditions. Project Number: EBJAX072, J6820701, 20 0514. Unpublished study prepared by Bayer Corp. 34 p.

46246011 2051015 2050895

- memo Heimbach, F. (1990) Acute Toxicity of SXX 0665 (techn.) to Waterfleas (Daphnia magna). Project Number: HBF/DM/95, E/3200404/1. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 28 p. Prothioconazole

– Desthio

46246012 2051016 2050895

- memo Dorgerloh. M.; Sommer, H. (2001) Acute Toxicity of JAU6476

- S

- Methyl to Waterfleas (Daphnia magna). Project Number: E/3202119/8, DOM/21055, 00699/MR/250/01. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 40 p.

46246028 2051007 Hendel, B.; Sommer, H. (2001) Influence of JAU6476 (tech.) on the Reproduction Rate of Water Fleas. Project Number: E/3211982/6, HDB/RDM67. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 79 p.

47626901 2084467208 4450

- memo Picard, C. R. (2008) JAU 6476

- Desthio

- Full Life

- Cycle Toxicity Test with Sediment

- Dwelling Midges (Chirnomus riparius) Under Static Conditions: Following OECD Gu ideline 218: (Prothioconazole Technical, Proline 480 SC Fungicide, Provost 433 SC Fungicide). Project Number: 13798/6219, EBJAY008, 2000BRP213/183. Unpublished study prepared by Springborn Smithers Laboratories. 91

46246013 2051017 Sayers, L. (2004) JAU 6 476

- Desthio

- Acute Toxicity to Crayfish (Promcambarus clarkii) Under Static

- Renewal Conditions: Amended Final Report. Project Number: 13798/6147, EBJAY004, J6880601. Unpublished study prepared by Springborn Smithers Laboratories. 49 p.



### 72

- 3 Acute T oxicity to Estuarine/Marine Organisms

MRID Citation Reference

46246014 2050898 2050895

- memo Drottar, K.; Kendall, T.; Krueger, H. (2001) JAU 6476: A 96

- Hour Shell Deposition Test with the Eastern Oyster (Crassostrea virginica). Project Number: 149A/127, J6831501, 110956. Unpublished study prepared by Wildlife International, Ltd. 39 p.

46246016 2050899 2050895

- memo Drottar, K.; Blankinship, A.; Kendall, T.; et. al. (2002) JAU 6476: A 96

- Hour Flow

Through Acute Toxicity Test with the Saltwater M ysid (Mysidopsis bahia). Project Number: 149A/128A, J6833101, 110983. Unpublished study prepared by Wildlife International, Ltd. 38 p.

### 65 46246017 2050897 2050895

- memo Drottar, K.; Palmer, S.; Kendall, T.; et. al. (2002) Desthio JAU 6476: A 96

- Hour Flow

- Through Acute Toxicity Test with the Saltwater Mysid (Mysidopsis bahia). Project Number: 149A/129, J6833102, 110979. Unpublished study prepared by Wildlife International, Ltd. 39 Desthio metabolite

46246027 2051008 2050895

- memo Kern, M.; Lam, C. (2004) Acute Toxicity of JAU 6476 Technical to the Sheepshead Minnow (Cyprinodon variegatus) Under Static

- Renewal Conditions. Project Number: EBJA2140, J6830901, 200615. Unpublished study prepared by Bayer Corp. 35 p.



### 72

- 4 Fish Ea rly Life Stage/Aquatic Invertebrate Life Cycle Study

MRID Citation Reference

46246028 2051007 2050895

- memo Hendel, B.; Sommer, H. (2001) Influence of JAU6476 (tech.) on the Reproduction Rate of Water Fleas. Project Number: E/3211982/6, HDB/RDM67. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 79 p.

46246029 2051006 2050895

- memo Dorgerloh, M.; Sommer, H. (2001) Influence of JAU6476

- Desthio on the Reproduction Rate of Water Fleas in a Static Renewal Laboratory Test System. Project Number: E/3211987/5, DOM/21036. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 73 p. Desthio metabolite

46246030 2050896 2050895

- memo B lankinship, A.; Kendall, T.; Krueger, H. (2003) Desthio JAU

- 6476: A Flow

Through Life Cycle Toxicity Test with the Saltwater Mysid (Mysidopsis bahia). Project Number: 149A/130A, J6843101, 200485. Unpublished study prepared by Wildlife International, Ltd. 107 p Desthio metabolite

46246031 2051005 2050895

- memo Dorgerloh, M.; Sommer, H. (2001) JAU6476

- Early Life Stage Toxicity to Rainbow Trout (Oncorhynchus mykiss) Under Flow

- through Conditions. Project Number: E/2841699/9, DOM/20028, 00586. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analy tik. 102 p.

46246032 2051004 2050905 2050895

- memo Gries, T.; Dorgerloh, M. (2002) JAU6476

- Desthio : Early Life

- Stage Toxicity Test with Rainbow Trout (Oncorhynchus mykiss) Under Flow

- Through Conditions. Project Number: 1022/013/321. Unpublished study prepared by Springborn Laboratories (Europe) Ag. 119 p. Desthio metabolite



### 72

- 5 Life cycle fish

MRID Citation Reference

46246033 2051003 2050895

- memo Drottar, K.; Kendall, T.; Krueger, H. (2004) Desthio JAU 6476: A Flow

- Through Life

- Cycle Toxicity Test with the Fathead Minnow (Pimephales promelas). Project Number: 149A/126A, J6851201, 200108. Unpublished study prepared by Wildlife International, Ltd. 130 p. Desthio metabolite



### 72

- 6 Aquatic org. accumulation

MRID Citation Reference

### 66 46246034 2050583 2050414 Dorgerloh, M.; Weber, E. (2001) (Carbon 14)

- JAU6476

- Bioconcentration and Biotransformation in Bluegill (Lepomis macrochirus) Under Flow

- Through Conditions. Project Number: E/2442023/7, DOM/21003. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 168 p.

46246035 2050584 2050414 Dorgerloh, M.; Weber, E.; Spiegel, K. (2001) (Carbon 14)

- JAU6476

- Desthio

- Bioconcentration and Biotransformation in Bluegill (Lepomis macrochirus) Under Flow

- Through Conditions. Project Number: E/2441731/2, DOM/20006. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 131 p. Desthio metabolite



### 122

- 1 Seed Germination/Seedline Emergence and Vegetable Vigor

MRID Citation Reference

46246049 2050902 2050895

- memo Sabbert, T. (2004) Tier 1 Seedling Emergence and Vegetative Vigor Non

- target Phytotoxicity Study Using JAU 6476 480 SC. Project Number: J6451601, J6451602, 200951. Unpublished study prepared by Bayer Corp. 84 p.

46246050 2050913 2050895

- memo Sabbert, T. (2004) Tier 2 Seedling Emergence Non

- target Phytotoxicity Study Using JAU 6476 480 SC. Project Number: J6451603, 200952. Unpublished study prepared by Bayer Corp. 57 p.



### 123

- 2 Aquatic plant growth

MRID Citation Reference

46246101 2050912 2050895

- memo Kern, M.; Banman, C.; Lam, C. (2004) Toxicity of JAU 6476 Technical to Duckweed (Lemna gibba G3) Under Static

- Renewal Conditions. Project Number: EBJAY002, J6883701, 200488. Unpublished study prepared by Bayer Corp. 48 p.

46246102 2050911 2050895

- memo Kern, M.; Banman, C.; Lam, C. (2003) Toxicity of JAU 6476 480 SC to Duckweed (Lemna gibba G3) Under Static

- Renewal Conditions. Project Number: EBJAX189, J6883703, 200672. Unpublished study prepared by Bayer Corp. 48 p.

46246103 2050910 2050895

- memo Kern, M.; Roberts, J.; De Haan, R. (2004) Toxicity of JAU 6476 Technical to the Blue

- green Alga Anabaena flos

- aquae. Project Number: EBJAX078, J6883801, 200497 . Unpublished study prepared by Bayer Corp. 58 p.

46246104 2050909 2050895

- memo Kern, M.; Banman, C.; Lam, C. (2003) Toxicity of JAU 6476

- Desthio to Duckweed (Lemna gibba G3) Under Static

- Renewal Conditions. Project Number: EBJAX084, J6883702, 200469. Unp ublished study prepared by Bayer Corp. 46 p. Desthio metabolite

46246105 2050908 2050895

- memo Dorgerloh, M. (2000) JAU6476 Influence on the Growth of the Green Alga, Selenastrum capricornutum. Project Number: E/3231610/6, DOM/99107. Unpublished study pre pared by Bayer Ag Institut fuer Ruckstands

- Analytik. 49 p.

46246106 2050907 Kern, M.; Lam, C. (2004) Toxicity of JAU 6476 480 SC Formulation to the Green Alga Pseudokirchneriella subcapitata (a.k.a. Selenastrum

### 67 capricornutum). Project Number: EBJAX075, J6883501, 200602. Unpublished study prepared by Bayer Corp. 51 p.

46246107 2051024 2050895

- memo Dorgerloh, M.; Sommer, H. (2001) JAU6476

- S

- Methyl Influence on the Growth of the Green Alga, Selenastrum capricornutum. Project Number: E/3232061/7, DOM/21028. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

Analytik. 48 p.

46246108 2051022 Heimbach, F. (1990) Growth Inhibition of Green Algae (Scenedesmus subspicatus) by SXX 0665 Technical. Project Number: E/3230401/3, HBF/AL78. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

Analytik. 30 p. Prothioconazole

- Desthio

46246109 2051023 2050895

- memo Kern, M.; Lam, C. (2004) Toxicity of JAU 6476 Technical to the Freshwater Diatom Navicula pelliculosa. Project Number: EBJAX085, J6883401, 200252. Unpublished study prepared by Bayer Corp. 50 p.

46246110 2050903 2050895

- memo Kern, M.; De Hann, R. (2004) Toxicity of JAU 6476 Technical to the Saltwater Diatom Skeletonema costatum. Project Number: EBJAX076, J6883601, 200434. Unpublished study prepared by Bayer Corp. 49 p.

462461 31 205090620 50895 Heimbach, F. (1990) Growth Inhibition of Green Algae (Scenedesmus subspicatus) by SXX 0665 Technical. Project Number: E/3230401/3, HBF/AL78. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

Analytik. 30 p. Desthio metabolite



### 141

- 1 850.3020 Honey bee acute contact

MRID Citation Reference

46246046 2050900 2050895

- memo Schmitzer, S. (2004) Effects of JAU 6476 SC 480 (Acute Contact and Oral) on Honey Bees (Apis mellifera L.) in the Laboratory. Project Number: 18351035. Unpublished study prepared by Institut fuer Biologische Analytik und Consulting IBA CON GmbH. 31 p.

46246048 2050901 2050895

- memo Wilhelmy, H. (1999) JAU 6476 a.i.: Acute Effects on the Honeybee Apis mellifera. Project Number: IBA64051, 990222BN. Unpublished study prepared by Dr. U. Noack

- Laboratorium fuer Angewandte Biologie. 32 p.



### 850.1790 Chironomid Sediment Toxicity Test

MRID Citation Reference

46246131 2050906 Hendel, B. (2000) Influence of JAU6476 (tech.) on Developmental and Emergence of Larvae of Chironomus riparius in a Water

- Sediment System. Project Number: E/4161775/1, HDB/CH42. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 53 p.

46246132 2050905 Hendel, B. (2000) Influence of SXX 0665 (tech.) on Development and Emergence of Larvae of Chironomus riparius in a Water

- Sediment System.

### 68 Project Number: E/4161808/8, HDB/CH43. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 53 p. Prothioconazole

– Desthio metabolite 

### Non

- Guideline Studies
MRID Citation Reference

46246132 2050905 2050895 Hendel, B. (2000) Influence of SXX 0665 (tech.) on Development and Emergence of Larvae of Chironomus riparius in a Water

- Sediment System. Project Number: E/4161808/8, HDB/CH43. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 53 p. Desthio metabolite

46246013 2051017 Sayers, L. (2004) JAU 6476

- Desthio

- Acute Toxicity to Crayfish (Promcambarus clarkii) Under Static

- Renewal Conditions: Amended Final Report. Project Number: 13798/6147, EBJAY004, J6880601. Unpublished study prepared by Springborn Smithers Labora tories. 49 p. Desthio metabolite

46246015 2050958 Kendall, T.; Nixon, W. (2001) Analytical Method Verification for the Determination of JAU

- 6476 in Saltwater. Project Number: 149C/115, J6112401, 110957. Unpublished study prepared by Wildlife Internati onal, Ltd. 30 p.

46246041 DER not

located Martin, K.; Nixon, W. (2001) Analytical Method Verification for the Determination of Desthio JAU 6476 in Avian Diet. Project Number: 149C/113, J6111901, 99/B/203. Unpublished study prepared by Wildlife International, Ltd. 30 p.

46246118 DER not located Nienstedt, K. (2002) Reproduction Toxicity Test Exposing Folsomia candida (Collembola) to JAU6476 Technical. Project Number: 1022/028/641. Unpublished study prepared by Springborn Laboratories (Europe) Ag. 34 p

4 6246119 DER not located Moser, T.; Rombke, J. (2001) Acute and Reproduction Toxicity of JAU6476

- Desthio to the Collembolan Species Folsomia candida According to the ISO Guideline 11267 "Soil Quality

- Inhibition of Reproducti on of Collembola (Folsomia candida) by Soil Pollutants" (1999). Project Number: P1CR. Unpublished study prepared by ECT Oekotoxikologie Gmbh. 28 p. Desthio metabolite

46246120 Nienstedt, K. (2001) Reproduction Toxicity Test Exposing Folsomia Candida (Col lembola) to JAU6476

- Desthio. Project Number: 1022/020/641. Unpublished study prepared by Springborn Laboratories (Europe) Ag. 36 p. Desthio metabolite

46246 1 21 Moser, T.; Scheffczyk, A. (2001) Acute and Reproduction Toxicity of JAU6476

- S

- Methyl to the Collembolan Species Folsomia candida According to the ISO Guideline 11267 "Soil Quality

- Inhibition of Reproduction of Collembola (Folsomia candida) by Soil Pollutants" (1999). Project Number: P35CR. Unpublished study prepared by ECT Oekotoxikologie Gmbh. 2 4 p.

46246122 Meisner, P. (2000) Acute Toxicity of JAU6476 (tech.) to Earthworms (Eisenia fetida). Project Number: E/3101769/7, MPE/RG326/00. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 22 p.

46246123 Meisner, P. (2000) Ac ute Toxicity of JAU6476 EC 250 to Earthworms (Eisenia fetida). Project Number: E/3101795/6, MPE/RG331/00. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 18 p.

46246124 Lechelt

- Kunze, C. (2003) Prothioconazole (JAU 6476) SC 480: Acute Toxicity to Earthworms (Eisenia fetida) Tested in Artifical Soil with 10% Peat. Project Number: E/3102600/2, LKC/RG/A/16/03. Unpublished study prepared by Bayer Ag, Institute of Product Info. 23 p.

### 69 46246125 Meisner, P. (2000) Acute Toxicity of JAU 6476

- Desthio to Earthworms (Eisenia fetida). Project Number: E/3101844/1, MPE/RG338/00. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 20 p. Desthio metabolite

46246126 Heimbach, F. (2000) Acute Toxicity of JAU6476

- S

- Methyl to Earthworms (Eisenia fetida). Project Number: E/3101743/9, HBF/RG321. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 19 p.

46246127 Meisner, P. (2000) Influence of JAU6476

- EC 250 on the Reproduction of Earthworms (Eisenia fetida ). Project Number: E/3121753/2, MPE/RG325. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 27 p.

46246128 Meisner, P. (2000) Influence of JAU6476

- Desthio on the Reproduction of Earthworms (Eisenia fetida). Project Number: E/3121 799/2, MPE/RG322/00. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 24 p. Desthio metabolite

46246129 Heimbach, F. (2000) Influence of JAU6476

- S

- Methyl on the Reproduction of Earthworms (Eisenia fetida). Project Number: E/31217 13/8, HBF/RG317. Unpublished study prepared by Bayer Ag Institut fuer Ruckstands

- Analytik. 24 p.

46246329 Becker, H.; Biedermann, K. (1991) Dose Range

- Finding Embryotoxicity Study (Including Teratogenicity) with SXX 0665 Technical in the Rabbit (Dermal A pplication). Project Number: 309554, R5425, T1040386. Unpublished study prepared by RCC Umweltchemie Ag. 92 p.

46246330 Becker, H.; Biedermann, K. (1997) Dose Toleration Study to a Developmental Toxicity Study with JAU 6476 in the Rabbit. Project Number: 650970, R7003, T/5055258. Unpublished study prepared by RCC Umweltchemie Ag. 112 p.

46246415 Schmidt, U. (1999) JAU 6476 Investigation of the Inhibition of Cytochrome P450 Dependent Monooxygenases in Liver Microsomes (in vitro). Project Number: 28400, 1 09060. Unpublished study prepared by Bayer Ag Inst. of Toxicology. 20 p.

46246440 Moore, K.; Budzowski, K. (1998) A Liquid Chromatographic Method for the Determination of JAU 6476 in Dose Preparations. Project Number: 98/899/RI, 108384. Unpublished study prepared by Bayer Corp. 16 p.

46246441 Rinke, M. (2001) Assessment of Ovarian Findings in Rodents After Treatment with SXX0665. Project Number: MO/02/000457. Unpublished study prepared by Bayer Ag Inst. of Toxicology. 15 p.

46246442 Stropp, G. (1996) Validation of the Magnusson

- Kligman Maximization Test Method Used by the Fachbereich Toxlkologie, Bayer AG Performed in Guinea Pigs of the Strain Hsd Poc: DH. Project Number: T/1060339, 24605. Unpublished study prepared by Bayer Ag Inst. of Toxicology. 31 p.

46246443 Vohr, H. (2002) Validation of the Magnusson

- Kilgman Maximization Test Method Used by the Fachbereich Toxikologie, Bayer AG Performed in Guinea Pigs of the Strain Crl:HA with Alpha

- Hexylzimtaldehyd. Project Number: T/8071893, AT00083. Unpublished study prepared by Bayer Ag Inst. of Toxicology. 30 p.

46246444 Moore, K. (1991) A Liquid Chromatographic Method for the Determination of SXX 0665 in Rodent Ration. Project Number: 101258. Unpublished study prepared by Mobay Chemical Corp. 18 p.

### 70 46246445 Tolliver, M. (2004) Tier II Summaries for Toxicology Studies. Project Number: 201003. Unpublished study prepared by Bayer CropScience LP. 474 p.

46467302 Wahle, B. (2004) A Subchronic Toxicity Testing Study in the CD

- 1 Mouse with 1,2,4

- Tria zole. Project Number: 03/S71/QC, 201052, TZ524902. Unpublished study prepared by Bayer Corp. and Bayer Ag Inst. of Toxicology and Dow Chemical Company. 765 p.

46501401 Robaugh, D. (2005) Dietary Exposure Monitoring: Determination of 1,2,4

- Triazole, Triaz ole Alanine and Triazole Acetic Acid Residues in Eggs. Project Number: U/S/TRIAZOLE/TASK/FORCE/1490, METH/160, U/S/TRIAZOLE/TASK/FORCE/1478. Unpublished study prepared by Pyxant Labs Inc. and Morse Laboratories, Inc. 351 p.

46616402 Jensen, T. (2004) The Homogeneity and Stability of 1, 2, 4

- Triazole Technical in Rodent Ration Using Purina Mills Certified Rodent Diet 5002 Meal. Project Number: 03/H72/RR, 201185. Unpublished study prepared by Bayer Corp. 15 p.

47626901 Picard, C. R. ( 2008) JAU 6476

- Desthio

- Full Life

- Cycle Toxicity Test with Sediment

- Dwelling Midges (Chirnomus riparius) Under Static Conditions: Following OECD Guideline 218: (Prothioconazole Technical, Proline 480 SC Fungicide, Provost 433 SC Fungicide). Project Number : 13798/6219, EBJAY008, 2000BRP213/183. Unpublished study prepared by Springborn Smithers Laboratories. 91 p.

48024309 Rupprecht, K.; Young, B. (2010) Tier 2 Summary of the Toxicological Studies and Exposure Data and Information on the Plant Protection P roduct for Penprome 177FS. Project Number: M/365048/01/1/OCR, M/365048/01/1, US0005. Unpublished study prepared by Bayer CropScience LP. 25 p.

48024311 Bulman, P.; Henry, S. (2010) Penprome 177FS Seed Treatment Fungicide. Project Number: M/365443/01/1/OC R, M/365443/01/1, BYFCAN007. Unpublished study prepared by Bayer CropScience. 1584 p.

48526701 Hall, T.; Tang, J.; Kwiatkowski, P. (2011) Bayer CropScience Response to US EPA Environmental Fate and Ecological Risk Assessment in Support of Prothioconazole Section 3 New Seed Treatment and Foliar Uses (December 13, 2010). Project Number: US0196. Unpublished study prepared by Bayer Cropscience LP. 24 p.

### 71 Appendix C. Prothioconazole Incidents A search for ecological incidents related to prothioconazole use, conducted o n August 27 , 2015, yielded 15 incidents . All of the incidents were classified as “possible” certainty (excludes incidents classified as ‘unlikely’ the result of or ‘unrelated’ to prothioconazole), which is summarized below.

Table C

. Prothioconazole Incidents, as Reported in the EIIS Database

Incident ID
# State, County Magnit ude Year Description Legality

I021485

- 021 MN, Otter Tail 500 Acres 2009 An application of the product Proline (a.i. prothioconazole) onto 500 acres of soybean in Otter Tail County, MN allegedly caused delayed maturity to 100% of the crop. Misuse

I022286

- 036 GA, Irwin 40 Acres 2010 On Aug 11, 2010 in Irwin County, GA, 100% of 40 acres of treated peanut crop suffered from leaf burn after being treated with the products Provost (a.i. prothioconazole, tebuconazole) and Asana XI (a.i. esfenvalerate). Alleged phytotoxic reaction to products following application to peanut crop. Undetermined

I022392

- 027 GA, Colquitt 50% of 460 Acres 2010 On August 23, 2010 in Colquitt County, GA 50% of 460 acres of peanut experienced leaf burn after the products Provost (a.i. prothioconazole, tebuconazole) and Sniper (a.i. bifenthrin) were applied. Alleged phytotoxic reaction to product following application to peanuts crop. U ndetermined

I023082

- 034 IA, Clinton 100% of 70
Acres 2011 On June 15, 2011 in Clinton County, IA 100% of 70 acres of corn was damage after the products Laudis (a.i. tembotrione), Stratego Yld (a.i. trifloxystrobin, prothioconazole), and Atrazine (non

- specific) was applied to the corn field. Alleged phytotoxic reaction to product following application to corn crop. The adverse effects included leaf wrapping, whitening at 3 leaf or later. The Compliance Manager for the Registrant noted an applic ation error and off label use. Misuse (intentional)

I023082

- 051 IL, Tazewell 47.6% 2011 On June 9, 2011 in Tazewell County, IL 47.6% of 40 acres of corn exhibited leaf burn after an application of the products Stratego Yld (a.i. Trifloxystrobin and prothioconazole), Capreno (a.i. thiencarbazone and tembotrione) and atrazine (non

- specific). Alleged phytotoxic reaction to product following application to corn crop. The Compliance Manager for the Registrant suggested the probable cause was high tempe ratures. Undetermined

I023302

- 029 GA, Calhoun 100% of 210
Acres 2011 In Calhoun County, GA, on August 29, 2011 100% of 210 acres of peanuts experienced leaf burn and leaf loss after an application of the product Provost (a.i. prothioconazole and a.i. tebuconazole) was used. The grower noticed leaf burn several days after the application. Grower alleges that aerial applicator applied only a mixture of provost and water. Application was made during a day when temperatures reached nearly 100 degrees. D ue to heat and humidity and possible water evaporation of the spray carrier could have led to a more concentrated amount of provost being sprayed on the peanuts. Grower alleges phytotoxic reaction to product following application to peanuts crop. Applic ation method: Aerial. Registered Use

I023302

- 030 GA, Wilcox 100% of 100
Acres 2011 In Wilcox County, GA, on August 17, 2011 100% of 100 acres of a peanut crop experienced leaf burn and leaf drop after a commercial application of the product Provost (prothioconazole and tebuconazole) . Alleged phytotoxic reaction to product following application to the peanut crop. Field agent for the Registrant suggested high temperatures and the grower mixing dimilin and boron with Provost as the probable cause. R egistered Use

I023302

- 031 GA, Dooly 100% of 155
Acres 2011 On August 19, 2011 in Dooly County GA 155 acres of peanuts was suffered leaf burn and leaf loss after the application of the products Provost (a.i. prothioconazole and a.i. tebuconazole)and Bifenthrin (a.i bifenthrin). Alleged phytotoxic reaction to product following application to peanut crop. The Registrant concluded the probable cause was high temperature. Registered Use

I023302

- 038 GA, Colquitt 525 Acres 2011 In Colquitt County, Ga. on Aug 23, 2011 100% of 525 treated acres of peanuts displayed symptoms of leaf burn and leaf drop. The commercially applied products Provost (a.i. prothioconazole) and FenvaloStar (a.i. esfenvalerate) are alleged to cause phytotoxic reaction. Registered Use

I023390

- 022 GA, Wilcox 100% of 100 Acres 2011 On August 8, 2011 in Wilcox County, GA 100% of 100 acres of peanuts exhibited leaf burn and leaf drop after the product Provost (a.i. prothioconazole, tebuconazole) was applied. Alleged phytotoxic reaction to product following application to peanut crop. The Registrant suggested high temperatures may have been the cause of the leaf burn. Registered Use

I023554

- 008 FL, Santa Rosa 56% of 450 Acres 2011 September 1, 2011 in Santa Rosa County, FL it was first observed 253 acres of peanuts were exhibiting severe leaf burn and leaf drop. Earlier in the growing season the peanuts were sprayed with Provost (a.i. prothioconazole and tebuconazole). The incident is under investigation. Undetermined

I024295

- 045 IL, Lawrence 100% of 64 Acres 2012 On June 6, 2012 in Lawrence County, IL 100% of 64 acres of small grains may have experienced desiccation and phytotoxic reaction to the products Prosaro (a.i. prothioconazole) and Baythroid Xl (a.i. beta

- cyfluthrin). Alleged phytotoxic reaction to product following application to the small grain crop. Investigation predetermined from the spray pattern there was a minor tank contamination in one of the loads. Registered Use

### 72 Incident ID
# State, County Magnit ude Year Description Legality

I024295

- 047 GA, Thomas 100% of 7
Acres 2012 On June 22, 2012 in Thomas County, GA 100% of 7 acres of peanuts experienced leaf burn after the product Proline (a.i. prothioconazole) was applied. Alleged phytotoxic reaction to product following application to peanuts crop. The representative for the Registr ant suggested the probable cause may have been tank mix partner. Registered Use

I024431

- 042 ND, Griggs 100% of 400
Acres 2012 On July 2, 2012 in Griggs County, ND 100% of 400 acres of spring wheat desiccated after the application of the product Prosaro 421 SC Fungicide (a.i. prothioconazole, tebuconazole). Alleged phytotoxic reaction to product following application to spring wheat crop. Adverse effects; showed desiccation. The Registrant suggested the probable cause was tank contamination. Waiting f or lab results. Misuse

I025344

- 022 ND, County not listed 100% of 120
Acres 2013 Allegedly an application of the product Ernesto Silver (a.i. prothioconazole) resulted in a phytotoxic reaction to 100% of 120 acres of a potato crop. Undetermined



### Uncertainties Related to the Use of Incident Information from the Ecological Incident Information System Incident data are used in risk assessments to provide evidence that the risk predictions from the screening level assessment are supported by actual effects in the field. Incident reports submitted to EPA since approximately 1994 have been tracked by assignment of incident numbers in an Incident Data System (IDS), microfiched, and then entered to a second database, the Ecological Incident Information System (EIIS). Additionally, there is an on

- going effor t to enter information to EIIS on incident reports received prior to establishment of current databases. Incident reports are not received in a consistent format ( e.g ., states and various labs usually have their own formats), may involve multiple incident s involving multiple chemicals in one report, and may report on only part of a given incident investigation ( e.g ., residues).
Incidents entered into EIIS are categorized into one of several certainty levels regarding the likelihood that a particular pesticide is associated with the incident: highly probable, probable, possible, unlikely, or unrelated. In brief, “highly probable” incidents usually require carcass residues and/or clear circumstances regarding the exposure. “Probable” incidents include those where residues were not available and/or circumstances were less clear than for “highly probable.” “Possible” incidents include those where multiple chemicals may have been involved and it is not clear what the contribution was of a given chemical. The “unlikely” category is used, for example, where a given chemical is practically nontoxic to the category of organism killed and/or the chemical was tested for but not detected in samples. “Unrelated” incidents are those that have been confirmed to be not pesticide

- related.
Incidents entered into the EIIS are also categorized as to use/misuse. Unless specifically confirmed by a state or federal agency to be misuse, or there was very clear misuse such as intentional baiting to kill wildlife, incidents are not typically considered misuse.

The number of documented kills in EIIS is believed to be a small fraction of total mortality caused by pesticides. Mortality incidents must be seen, reported, investigated, and have investigation reports submitted to EPA to have the potential for entry into the database. Incidents often are not seen, due to scavenger removal of carcasses, decay in the field, or simply because carcasses may be hard to see on many sites and/or few people are systematically looking. Poisoned animals may also move off

- site to less conspicuous areas before dying. Incidents may not get reported to appropriate authorities capable of investigating the incident for a variety of reasons including the finder may not know of the importance of reporting incidents, may not know who to call, may not feel they have the time or desire to call, or may hesitate to call because of their own involvement in the kill. Incidents reported may not get investigated if resources are limited or may not get in vestigated

### 73 thoroughly, with residue analyses, for example. Also, if kills are not reported and investigated promptly, there will be little chance of documenting the cause, since tissues and residues may deteriorate quickly. Reports of investigated incide nts often do not get submitted to EPA, since reporting by states is voluntary.
Furthermore, the database relies heavily on registrant

- submitted incident reports, and registrants are currently only required to submit detailed information on ‘major’ ecolo gical incidents, while ‘minor’ incidents are reported aggregately. Based on the 40 CFR (§159.184 Toxic or adverse effect incident reports), an ecological incident is considered ‘major’ if any of the following criteria are met:

Fish or wildlife : (A) Invo lves any incident caused by a pesticide currently in Formal Review for ecological

concerns. (B) Fish: Affected 1,000 or more individuals of a schooling species or 50 or more individuals of a non

- schooling species.
(C) Birds: Affected 200 or more indivi duals of a flocking species, or 50 or more individuals of a songbird species, or 5 or more individuals of a predatory species. (D) Mammals, reptiles, amphibians: Affected 50 or more individuals of a relatively common or herding species or 5 or more indiv iduals of a rare or solitary species. (E) Involves effects to, or illegal pesticide treatment (misuse) of a substantial tract of habitat (greater than or equal to 10 acres, terrestrial or aquatic).

Plants : (A) The effect is alleged to have occurred on more than 45 percent of the acreage exposed to the pesticide.
All other ecological incidents are considered ‘minor’ and only need to be aggregately reported. ‘Minor’ incidents reported by the registrants are not included in the EIIS database. Therefore , for example, an incident could affect 900 fish, 150 birds, 45 mammals, and 40% of an exposed crop and not be included in the EIIS database [unless is it reported by a non

- registrant ( e.g ., an incident submitted by a state agency

– which are not systemati cally collected)]. Therefore, because the number of documented kills in EIIS is believed to be a small fraction of total mortality caused by pesticides, absence of reports does not necessarily provide evidence of an absence of incidents.

### 74 Appendix D

. Example SIP Result for Prothioconazole Parent Compound
Inputs

Parameter Value
Chemical name Prothio

- Parent
Solubility (in water at 25 o C; mg/L) 344

Mammalian LD 50 (mg/kg

- bw) 6200 Mammalian test species laboratory rat Body weight (g) of "other" mammalian species

Mammalian NOAEL (mg/kg

- bw) 100 Mammalian test species laboratory rat Body weight (g) of "other" mammalian species

Avian LD 50 (mg/kg

- bw) 2000 Avian test species northern bobwhite quail Body weight (g) of "other" avian species Mineau scaling factor 1.15

Mallard NOAEC (mg/kg

- diet) 982 Bobwhite quail NOAEC (mg/kg

- diet) 0 NOAEC (mg/kg

- diet) for other bird species Body weight (g) of other avian species NOAEC (mg/kg

- diet) for 2nd other bird species Body weight (g) of 2nd other avian species

Mammalian Results

Parameter Acute Chronic Upper bound exposure (mg/kg

- bw) 59.1680 59.1680 Adjusted toxicity value (mg/kg

- bw) 4768.7955 76.9161 Ratio of exposure to toxicity 0.0124 0.7693

Conclusion* Drinking water exposure alone is NOT a potential concern for mammals Drinking water exposure alone is NOT a potential concern for mammals

Avian Results

Parameter Acute Chronic Upper bound exposure (mg/kg

- bw) 278.6400 278.6400 Adjusted toxicity value (mg/kg

- bw) 1440.8590 48.7195 Ratio of exposure to acute toxicity 0.1934 5.7193

Conclusion* Exposure through drinking water alone is a potential concern for birds Exposure through drinking water alone is a potential concern for birds

*Conclusion is for drinking water exposure alone. This does not combine all routes of exposure. Therefore, when aggregated with other routes ( i.e ., diet, inhalation, dermal), pesticide exposure through drinking water may contribute to a total exposure that has potential for effects to non

- target animals.

### 75 Appendix E . STIR Results

Input

Application and Chemical Information

Enter Chemical Name Prothioconazole
Enter Chemical Use
Is the Application a Spray? (enter y or n) y If Spray What Type (enter ground or air) air Enter Chemical Molecular Weight (g/mole) 344.264 Enter Chemical Vapor Pressure (mmHg) 3.00E

- 09 Enter Application Rate (lb a.i./acre) 0.178

Toxicity Properties

Bird
Enter Lowest Bird Oral LD 50 (mg/kg bw) 2000 Enter Mineau Scaling Factor 1.15 Enter Tested Bird Weight (kg) 0.178
Mammal

Enter Lowest Rat Oral LD 50 (mg/kg bw) 6200

Enter Lowest Rat Inhalation LC 50 (mg/L) 4.99 Duration of Rat Inhalation Study (hrs) 4 Enter Rat Weight (kg) 0.35

Output
Results Avian (0.020 kg ) Maximum Vapor Concentration in Air at Saturation (mg/m 3 ) 5.56E

- 05

Maximum 1

- hour Vapor Inhalation Dose (mg/kg) 6.99E

- 06
Adjusted Inhalation LD 50 8.98E+00

Ratio of Vapor Dose to Adjusted Inhalation LD 50 7.78E

- 07 Exposure not Likely Significant

Maximum Post

- treatment Spray Inhalation Dose (mg/kg) 1.71E

- 02

Ratio of Droplet Inhalation Dose to Adjusted Inhalation LD 50 1.91E

- 03 Exposure not Likely Significant

Results Mammalian (0.015 kg ) Maximum Vapor Concentration in Air at Saturation (mg/m 3 ) 5.56E

- 05

Maximum 1

- hour Vapor Inhalation Dose (mg/kg) 8.78E

- 06
Adjusted Inhalation LD 50 2.97E+02

Ratio of Vapor Dose to Adjusted Inhalation LD 50 2.96E

- 08 Exposure not Likely Significant

Maximum Post

- treatment Spray Inhalation Dose (mg/kg) 2.15E

- 02

Ratio of Droplet Inhalation Dose to Adjusted Inhalation LD 50 7.24E

- 05 Exposure not Likely Significant