Page 1 of 41 OFFICE OF CHEMICAL SAFETY
AND POLLUTION PREVENTION 

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

October 23 , 2015

PC Code: 128993
MEMORANDUM DP Barcode: 429082

SUBJECT: EFED and AD Registration Review Problem Formulation for Cyproconazole

FROM: Elyssa Arnold , Biologist Edmund Wong

, Environmental Chemist
Environmental Risk Branch 2 Environmental Fate and Effects Division ( 7507P)

James Breithaupt, Agronomist Daniel Cherry, Biologist Risk Assessment and Science Support Branch (RASSB) Antimicrobials Division (7510P)

REVIEWED Donna Judkins , Biologist
BY: Jim Lin , Environmental Engineer
Environmental Risk Branch 2 Environmental Fate and Effects Division ( 7507P)

THROUGH: Bri an Anderson, Branch Chief
Environmental Risk Branch 2 Environmental Fate and Effects Division ( 7507P)

Laura Parsons, Associate Branch Chief Risk Assessment and Science Support Branch (RASSB) Antimicrobials Division (7510P)

TO: Miguel Zavala, Chemical Review Manager Rachel Ricciardi, Chemical Review Manager, AD Tracy Perry, Team Leader Kelly Sherman, Branch Chief Risk Management and Implementation Branch 3
Pesticide Re

- evaluation Division (7508P)Page 2 of 41 

# Table of Contents

1. Executive Summary

................................ ................................ ................................ ................ 3
2. Introduction

................................ ................................ ................................ ............................. 4
2.1. Mode of A ction

................................ ................................ ................................ ................ 4
3. Use Characterization

................................ ................................ ................................ ............... 5
3.1. Conventional Uses

................................ ................................ ................................ ............ 5
3.2. Antimicrobial Uses

................................ ................................ ................................ ........... 5
4. Conclusions from Previous Risk Assessments

................................ ................................ ....... 6
4.1. Ecological Risk Assessment

................................ ................................ ............................. 6
4.2. Drinking Water Exposure Assessments

................................ ................................ ........... 7
4.3. Clean Water Act Programs

................................ ................................ ............................... 7
5. Environmental Fate and Transport

................................ ................................ .......................... 8
5.1. Chemical Identity

................................ ................................ ................................ ............. 8
5.2. Fate Summary

................................ ................................ ................................ .................. 8
5.3. Fate Ch aracterization

................................ ................................ ................................ ........ 8
5.4. Transformation Products

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

6. Receptors

................................ ................................ ................................ ............................... 14
6.1. Effects to Aquatic Organisms

................................ ................................ ........................ 14
6.2. Effects to Terrestrial Organisms

................................ ................................ .................... 15
6.3. Ecological Incidents

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

7. Exposure Pathways of Concern

................................ ................................ ............................ 18
8. Analysis Plan

................................ ................................ ................................ ........................ 18
8.1. Stressors of Concern

................................ ................................ ................................ ....... 18
8.2. Measures of Exposure

................................ ................................ ................................ .... 18
8.3. Measures of Effect

................................ ................................ ................................ ......... 19
8.4. Endangered Species Assessments

................................ ................................ .................. 19
8.5. Endocrine Disruptor Screening Program

................................ ................................ ....... 20
9. Preliminary Identification of Data Gaps

................................ ................................ ............... 20
9.1. Environmental Fate

................................ ................................ ................................ ........ 20
9.2. Effects

................................ ................................ ................................ ............................. 21
10. References

................................ ................................ ................................ .......................... 30
10.1. Submitted Environmental Fate Studies

................................ ................................ ...... 32
10.2. Submitted Ecological Toxicity Studies

................................ ................................ ...... 33 Appendix A. SIP Modeling Results

................................ ................................ .............................. 36 Appendix B. STIR Modeling Results

................................ ................................ ........................... 37 Appendix C. Half

- life Calculations

................................ ................................ .............................. 38Page 3 of 41 

# 1. Ex ecutive S ummary

The Environmental Fate and Effects Division (EFED) has completed the preliminary problem
formulation for the ecolog ical risk, environmental fate, endangered species, and drinking water assessments to be conducted as part of the registration review of the conventional uses of cyproconazole (PC 128993 )

. The Antimicrobials Division (AD) recently registered a new
antimicro bial product of cyproconazole as a wood preservative for structural lumber (USEPA,
2015 b )

. The Agency determined that no environmental exposures and, therefore, no risks, are expected from this use pattern. This product is currently the only registered AD product for cyproconazole. The new AD product (72616

- 9 ) contains 4.5% cyproconazole and 45% triadimefon. Several cyproconazole antimicrobial wood preservative products were voluntarily
cancelled by the registrant in 2013.

The EFED problem formulation describes the methods planned to be used during the completion of drinking water and ecological r isk assessments in support of registration review and provide s

an ove rview of the environmental fate, ecological effects

, potential risks a ssociated with the use,
and uncertain ties unique to the risk assessment of cyproconazole

. This document also identifies
additional studies that would be beneficial to the conduct of an ecological risk assessment.

Ecological risk assessments for uses of c yproconazole were conducted in 2005, 2007, 2011, and 2012 (USEPA 2005, 2007b, 2011, 2012). For registered outdoor use s, an a cute and chronic risk

concern w as identified for small birds eating short grass only

. A dditional risk concern s were identified for p roposed uses at higher application rates ; however, those uses were voluntarily
withdrawn

.

The following are the recommended data and uncertainties for cyproconazole.

Data Needs

• Environmental Fate and Transport Data

o Environmental Chemistry Method and Independent Laboratory Validation

 OCSPP 850.6100: Soil

 OCSPP 850.6100: Water

• Ecotoxicity Data

o Chronic estuarine/marine water column studies (TGAI)

 OCSPP 850.1350: Mysid chronic toxicity test

o Aquatic plant studies (TEP)

 OCSPP 850.4500: Algal toxicity, studies with freshwater diatom Navicula pelliculosa and marine diatom Skeletonema costatum

 OCSPP 850.4550: Cyanobacteria toxicity

o Avian studies (TGAI)

 OCSPP 850.2100: Avian acute toxicity

, passerine species

o Terrestrial invertebrate studies (TGAI)

 Non

- guideline (Tier 1) : Honey bee larvae acute toxicity

 Non

- guideline (Tier 1): Honey bee adult chronic oral toxicity

 Non

- guideline (Tier 1): Honey bee larvae chronic toxicityPage 4 of 41 

###  Non

- guideline (Tier 2): Semi

- field testing for polli nators (tunnel or colony feeding studies)

 Non

- guideline (Tier 2): Field trial of residues in pollen and nectar

 OCSPP 850.3040 (Tier 3): Field testing for pollinators

Label Uncertainties

For the use of cyproconazole on wheat and triticale, two of the four end use product labels do not specify the annual maximum application rate

. Absence of such information on the labels may result in conservative assumptions for modeling of use patterns in the registration review risk

assessment. Because cyproconazole is persistent in the environment, additional applications in a year are expected to result in buildup of the chemical in the environment and higher levels of exposure to wildlife.



# 2. Introduction

C y proconazole ( (2RS,3RS;2RS,3SR)

- 2

- (4

- chlorophenyl)

- 3

- cyclopropyl

- 1

- (1H

- 1,2,4

- triazol

- 1

- yl)butan

- 2

- ol )) is a broad spectrum, systemic, triazole fungicide in the conazole class registered for use on wheat, triticale, soy bean

, field and seed corn, and peanu ts

. Cyproconazole comprises
two diastereomers : 2 RS, 3 RS ;

- 2

- (4

- chlorophenyl)

- 3

- cyclopropyl

- 1

- (1 H

- 1,2,4

- triazol

- 1

- yl)butan

2

- ol and (2 RS, 3 SR )

- 2

- (4

- chlorophenyl)

- 3

- cyclopropyl

- 1

- (1 H

- 1,2,4

- triazol

- 1

- yl)butan

- 2

- ol

.

There are five active Section 3 registrations f or the conventional uses of cyproconazole in the United States. One is a technical registration (EPA Reg. No. 100

- 864), three are soluble concentrate formulations (EPA Reg. Nos. 100

- 1225, 100

- 1226, and 228

- 728), and one is a
flowable concentrate formulatio n (EPA Reg. No. 352

- 883). Cyproconazole is the sole active ingredient in one of the formulated products and it is co

- formulated with strobilurin fungicide s in the other three products.

EFED evaluated the most recent ecological risk assessments for cyproco nazole 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 registration review. Recent risk

assessments include 2005, 2007, 2011, and 2012 new use assessments (USEPA 2005, 2007b, 2011, 2012) . In addition, EFED considered the latest Agency science policies and risk assessment methodologies.



## 2.1. Mode of Action

Cyproconazole is a triazole fungicide belonging to the Group 3 class of compounds. Conazole fungicides disrupt normal fungal cell membrane structure and function primarily through inhibitions of ergosterol synthesis. Specifically, fungicidal activity occurs via inhibition of the action of cytochrome P450 (CYP)

- 51 (lanosterol 14α

- demethyl ase), which converts squalene to ergosterol, the predominant sterol component in cell membranes (White et al. , 1998; USEPA, 2010). Thus, conazole fungicides may be known as demethylation inhibitors (DMI) and sterol biosynthesis inhibitors (SBI). In mammals , the CYP51 reaction is part of the pathway leading to the biosynthesis of cholesterol (White et al. , 1998). Cholesterol is the primary sterol in the cellPage 5 of 41 

### membrane of mammalian cells, and is also required to make sex steroid hormones (Payne and Hales, 2004 ).



# 3. Use Characterization

3.1. Conventional Uses

Cyproconazole is applied as a foliar spray via aerial and ground application methods as well as
throu gh chemigation

. The four Section 3 end

- use products are Quadris Xtra ® Fungicide (EPA Reg. No. 100

- 1225 ; 7.3% cyproconazole, 18.2% azoxystrobin ) , Alto ® 100SL Fungicide (EPA Reg. No. 100

- 1226 ; 8.9% cyproconazole )

, AZURETM Xtra Fungicide (EPA Reg. No. 228

- 728 ; 7.3% cyproconazole, 18.2% azoxystr obin), and Dupont TM Aproach ® Prima Fungicide (EPA Reg. No. 352

- 88 3; 7.17% c yproconazole, 17.94% picoxystrobin). Cyproconazole targets a variety of fungal diseases and is registered for use on wheat, triticale, field and seed corn, soy, and peanuts

. The si ngle maximum application rate is 0.036 lbs active ingredient per acre ( a.i./ A ) for all registered uses

. The primary agricultural uses for cyproconazole are on soybeans ( < 2 .5 %
of cro p treated, 10,000 lbs a.i./yr) and wheat (<2.5% of crop treated, 20,000 lbs a.i./yr) (USEPA,
2015 a )

.

Table 1 lists the maximum use patterns for the labeled agricultural use sites. EFED will use application scenarios that result in maximum exposure scenarios for a giv en use for the risk

assessment. F or labels that do not include a maximum annual a pplication rate for wheat and triticale, conservative assumptions will be made based on the maximum possible wheat crops per

year.

Table 1 . Maximum Use Patterns for Current Uses of Cy proconazole

Use Max Single App. Rate (lbs a.i./A) Max App. Rate per
CC (lbs a.i./A) Max # of App. per CC Max App. Rate per

Year (lbs a.i./A) Max # of App. per

Year Min
Retreatment Interval (days) 2 Application
Methods

Wheat &
Triticale 2 0.036 0.036 NS NS 1 NS 14 Aerial spray,
Ground

spray, Chemigation Corn 2 0.036 0.036 2 0.036 2 7 Soybeans 0.036 0.072 NS 0.072 NS 14

Peanuts 0.036 0.072 NS 0.072 NS 28

N S = N ot S pecified; App.=A pplications ; CC=C rop C ycle

1 The labels for EPA Reg. No. 100

- 1226 and 352

- 883 specify an annual limit of 0.036 lbs a.i./A/yr for wheat and triticale. The labels for EPA Reg. No. 100

- 1225 and 228

- 728 only specify a seasonal limit, not an annual limit, for
wheat and triticale. More tha n one crop season per year is possible ( e.g. , spring and winter wheat).

2 For wheat, triticale, and corn, if a single application is made at the maximum rate, only one application can be made to that crop. If a lower rate is used, multiple applications are possible and the minimum retreatment intervals, which are specified on all of the Section 3 labels, apply.



## 3.2. Antimicrobial Uses

Cyproconazole is registered as a glueline addition to structural wood such as : oriented strand board, waferboard, fiberboard, and particleboard at 0.2

- 1.0 gallon of product /cu yd of compositePage 6 of 41 

### material , and plywood, laminated veneer lumber (LVL), and parallel strand lumber at 0.2

- 1.2 gallon/cu yd of lumber. The agency conducted a human health and ecological risk assessment,
which determined that environmental exposures are not anticipated from the glueline use, and
therefore

, no ecological assessment for the antimicrobial use of cyproconazole as a glueline
addition to structural wood is necessary ( USEPA, 201 5 b ).



# 4. Conclusions fr om Previous Risk Assessments

4.1. Ecological Risk Assessment

Previous ecological risk assessments for cyproconazole include a 2012 assessment for use on peanuts (USEPA, 2012), a 2011 assessment for a use on turf and field

- grown roses (USEPA, 2011), a 2007 assessment for use on soybeans, cereals, and corn ( USEPA, 2007 b ) , and a 2005 assessment for use on greenhouse roses (USEPA, 2005)

. For uses on peanuts, soybeans, cereals,
and corn (maximum single application rate of 0.036 lb a.i ./A) , acute and chronic LOC
exceedances were identified for small birds eating short grass. For use on turf and field

- grown roses, which were proposed at higher rates ( maximum single application rate of 0.37 and 0.09 lb
a.i./A , respectively ) , additional LO C exceedances were identified for mammals, terrestrial invertebrates, aquatic invertebrates, and terrestrial and aquatic plants. The proposal for the turf use has since been withdrawn and the use on roses was voluntarily cancelled by the registrant.
The wi thdrawal/voluntary cancellation followed an analysis of the impact on avian reproduction of alternate application rates and timing for the proposed turf use (USEPA, 2014). The use on greenhouse roses, which has been voluntarily cancelled by the registrant, was considered an indoor use so no ecological exposure was expected.

Figure 2 and Table 2 summarize the potential risks identified in previous assessments for currently approved uses and the supporting evidence

.

Figure 2 . Graphic Summary of Potential Risks from Current ly Registered Uses of CyproconazolePage 7 of 41 

### Table 2 . Evidence of Risk to Taxonomic Groups from Currently Regis tered Uses of Cyproconazole
Predominant Evidence of Negligible Risk Predominant Evidence of Risk

Mammals: No LOC exceedances Terrestrial plants: No LOC exceedances
Fish: No LOC exceedances Aquatic invertebrates: No LOC exceedances Aquatic plants: No LOC exceedances Birds: Acute and chronic risk LOC exceedances for small birds eating short grass.



### Limited Evidence of Negligible Risk Limited Evidence of Risk

Terrestrial invertebrates: Cyproconaz o le is practically

non

- toxic to adult h oney bees on an acute contact and
oral exposure basis. No chronic data or data on honey
bee larvae are available. None



## 4.2. Drinking Water Exposure Assessments

The latest drinking water assessment for cyproconazole was a Tier I Food Quality Protection Act (FQPA) drinking water exposure assessment conducted in 20 07

, based on registration of new

uses for spray application to cereals (wheat and triticale), corn, and soybeans (USEPA, 20 07 )

. Tier I FIRST modeling indicate s percent crop area corrected (PCA

- corrected) cyproconazole concentrations in surface source drinking water are not expected to exceed 1.14 μg/L for the annual peak concentration (1

- in

- 10

- year peak) and 0.11 μg/L for the annual concentration (1

- in

10

- year annual mean)

. For ground water, screening level exposure estimates using the T ier I SCI

GROW model indicat e the peak and chronic cyproconazole concentration in shallow groundwater is not expected to exceed 0.05 μg/L

. PRZM

- GW was not used in previous

assessments.

EDWCs for 1,2,4

- triazole, 1,2,4

- triazol e alanine, and 1,2,4

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

- derivative fungicides , including cyproconazole (USEPA, 2006a, 2006b). However, these degradates have not been identified as major degradates of cyproconazole in environmental fate studies (see Table 4 ).



## 4.3. Clean Water Act Programs

Cyproconazole is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act

. 1 

### No Total Maximum Daily Load (TMDL) criteria have been developed for cyproconazole

. 2 

### No a quatic life benchmarks have been established for cyproconazole

. 3 

### Any data submitted or otherwise located as part of the registration review process may be used to creat e aquatic life benchmarks if applicable.

1 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

2 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant _group_name=PESTICIDES

3 http://www.epa.gov/oppefed1/ecorisk_d ers/aquatic_life_benchmark.htmPage 8 of 41 

# 5. Environmental Fate and Transport

5.1. Chemical Identity

Cyproconazole is a mixture of four stereo

- isomers, two diastereomeric pairs of enantiomers : 2 RS, 3 RS ;

- 2

- (4

- chlorophenyl)

- 3

- cyclopropyl

- 1

- (1 H

- 1,2,4

- triazol

- 1

- yl)butan

- 2

- ol

. Diastereomers
have similar chemical properties but their physical properties are different

. Probable cyproconazole dissipation pathways are microbial

- mediated degradation, leaching, surface water runoff, and spray drift.



## 5.2. F ate Summary

Degradation of cyproconazole in soil is slow and is principally mediated by microorganisms
under aerobic conditions. Under sterile conditions or anaerobic conditions little or no degradation of cyproconazole was observed. Photolysis on soil an d volatilization were not degradation pathways. Cyproconazole is also stable to hydrolysis. The studies showed that as oxygen was depleted from soil (or water) or when temperatures decreased that the rate of degradation also decreased. Cyproconazole has m o derate mobility in most soils. If transported in
the environment , cyproconazole will degrade slowly in soil and have low to moderate sorption in
aerobic surface soils. Under anaerobic conditions, sorption appears to be the major dissipation pathway due to the lack of degradation

.



## 5.3. Fate Characterization

1. Persistence and Transformation : Cyproconazole is stable to hydrolysis and photodegradation in water

. The h alf

- life of cyproconazole is 89.2 days in a soil photolysis study . However, percent recoveries of cyproconazole decreased with proportionate increase
in bound residual solids (extracted with MeOH/H 2 

### O/MeOH) within the 37 day study period

, suggesting that the mechanism may be due to strong adsorption of cyproconazole to soil
overtime instead of photolysi s (MRID 40607707 ).

Cyproconazole slowly degrades in aerobic soil (t 1/2 

### = 1160 days , 90 th 

### percentile upper
confidence bound from 3 soils ) and aquatic environments (t 1/2 

### = 990 days

- stable ). In aerobic soil studies, half

- lives of cyproconazole range from 204 to 1360 days. T he only transformation product identified aside from CO 2 

### was triazolyl alanine ( 2

- amino

- 3

- (1

- H

- 1, 1, 2, 4

- triazol

- tyl) propanoic acid ) (MRID 41474401 ). In a supplemental study, MRID
42534801 , three soils were examined. Data from Flaach and Louisiana soils were unacceptable due to significant increases and fluctuations in fractions of volatiles (up to 63% ; with CO 2 

### accounted for an average of 33% ) that rendered the values unreliable for risk

assessment

, while no significant degradation of cyproconazole was observed in the North Carolina soil at 210 days study termination ( t 1/2 

### = >365). The s oil bound fraction of cyproconazole increased over time with direct correlation to study duration. The s oil bound
f raction maximum w as reported at 36.3% for North Carolina soil at 210 days (MRIDPage 9 of 41 

### 42534801)

. Meanwhile, in another aerobic soil metabolism study, the soil bound fraction
reached a maximum of 56% at study termination at 300 days (MRID 46840805).

In an aerobic aquatic study based on pond and river sediments from Switzerland, cyproconazole applied to water was found to move quickly into the sediment. The h alf

- life in

a pond water

- loam sediment system is 990 days and in a river water

- loam sediment system i s 2,310.5 days, although no major transformation products were observed and the only minor
transformation product was CO 2 

### (MRID 46840810 ). I n an anaerobic aquatic metabolism study, no degradation was observed for cyproconazole within the study duration of 365 days (MRID 43683201 ).

2. Transport and Mobility : Cyproconazole is low to moderately mobile in soil by the FAO Mobility Classification ( http://www.fao.org /DOCREP/003 /X2570E/X2570E06.htm ). The calculated Henry’s Law Constant of 7.1 x 10

- 10 

### atm∙m 3 

### ∙mol

- 1 

### at vapor pressure of 2.6 x 10

- 7 

### torr indicates that volatilization will not be a major route of dissipation.

Based on the batch equilibrium study, cyproconazole is moderately mobile in soils of low organic matter content. However, data also indicated that the compound is not readily susceptible to leaching over periods of less than 14 months (MRID 41441301 ). In the study, 94% of the applied material at 0.09 lb/A was retained by the soil column (74% in the upper 6 cm) and <1.0% was determined in the leachate.

3. Bioaccumulation : Cyproconazole has low bioaccumulation potential. It has bioconcentration factors in bluegill sunfish ( Lepomis macrochirus ) of 15X, 59X, and 34X in edible tissues,

non

- edible tissues , and whole fish, respectively. Metabolites in fish tissues are 2

- (4

- chlorophenyl)

- 3

- cyclopropyl

- 1

- (1H

- 1,2,4

- triazol

- 1

- yl)

- 2,3

- butanediol, 3

- (4

- chloropropyl

- 2

- cyclopropyl

- 4

- (1H

- 1,2,4

- triazole

- 1

- yl)

- 1,3

- butanediol.

4. Field Dissipation : Cyproconazole had a field dissipation half

- life of 19 2 days in a Maryland turf study , 252 days in an Oregon bare ground study, and 16 0 days in North Carolina study. Although cyproconazole was predominately detected in the surface soil layers (0

- 10 cm), there were occasional cyproconazole detections in 10 to 30 cm soil samples.

Non

- guideline foliar wash

- off and uptake studies on soybeans show foliar uptake of cyproconazole is substantially enhanced using adjuvant Nimbus (MRID 46840830). The half

life of cyproconazole on the outer surface of soybean leaves wa s 2. 5 days. Residues incorporated into the soybean leaves (defined as non

- washable fraction) had a half

- life of 9.5 days. The w ash

- off coefficient from soybean leaves was estimated at 0.214/cm or 21.4% of residual cyproconazole removed per cm of rainfall ( MRID 46950001).

Table 3 summarize s the chemical and environment al fate properties of cyproconazole.Page 10 of 41 

### Table 3

. Chemical Properties and Environmental Fate Parameters of Cyproconazole

Parameter Value Source

Selected Physical/Chemical Parameters

Molecular mass (molecular formula) 291.8 (C 15 H 18 ClN 3 O)
MRID 46840803 Vapor pressure (25°C) 2.6 x 10

- 7 torr (mm Hg)

Aqueous solubility 108 mg/L (2 2 ° C)
140 mg/L (2 5 ° C) Syngenta Number
T002995

- 05, 02

- 04

- 05;

Gardner et al. 2000 ;

MRID 46840803

Henry’s Law Constant (20°C) 7.1 x 10

- 10 atm*m3/mol USEPA 2011 D381967;
Calculated

O ctanol

- to

- water partition coefficient (log

K OW ) 2.90 HSDB

Persistence

Hydrolysis half

- life ( 50 ° C) Stable @ pH 4,5,7,9 MRID 46840804
MRID 40607706

Aqueous photolysis half

- life ( 25 ° C) Stable
MRID 40607707 Soil photolysis half

- life 1 89.2 days 2

Aerobic soil metabolism half

- life (2 0

- 25 ° C) 203.9 days
227.4 days 2 ,3

1360 days 2 >365 days (No significant degradation observed) MRID 46840806
MRID 46840805
MRID 41474401

MRID 42534801

Aerobic aquatic metabolism half

- life ( 20 ° C) Swiss river water

- loam sediment
system: 2310.5 days
Swiss pond water

- loam sediment
system: 990 days MRID 46840810

Anaerobic aquatic metabolism half

- life ( 24 ° C) Stable MRID 43683201

Mobility

Batch Equilibrium Koc (L/kg

- OC) Gilroy Loam

– 309 Gilroy Sediment

- 369 Biggs Clay

– 258 German Loamy sand

- 711
Keaton sandy loam

- 173 MRID 40607709

MRID 41441301

Partition Coefficients; Freundlich K f and 1/n Soil Kf 1/n Gilroy Loam 4.1 0.84 Gilroy Sediment 4.9 0.86 Biggs Clay 1.3 0.87 German Loamy sand 17 0.84 Keaton sandy loam 16 0.90 Harvey, 2004 p.74

- 79Page 11 of 41 Parameter Value Source

Field Dissipation

Terrestrial field dissipation half

- life; leaching depth 252 days

- OR @ 4 apps

- 0.38 lbs/A 160 days

- NC @ 4 apps

- 0.38 lbs/A 192 days

- MD turf @4 apps

- 0.38 lbs/A MRID 41800701
MRID 42430701
MRID 41800702
MRID 42430702
MRID 41384102

Fish Bioconcentration

Fish bioconcentration factors (steady

- state); depuration rate Bluegill Sunfish
Edible Tissues 15X

Non

- edible Tissues 59X
Whole Fish 34X MRID 40624302
MRID 40624303

NA: Not Available

1 Temperature not specified

2 Values recalculated with PESTDF Software . Calculations in Appendix C

. 3 Value is the mean from 5 test concentrations

.



## 5.4. Transformation Products

Triazolyl alanine ( 2

- amino

- 3

- (1

- H

- 1, 1, 2, 4

- triazol

- tyl) propanoic acid ) was identified as a minor metabolite of cyproconazole at 0.6% applied radioactivity at day 365 in an aerobic soil metabolism study (MRID 41474401 ). CO 2 

### was found in both aerobic soil metabolism study (7.9% at 112 days, MRID 46840806) and aerobic aquatic metabolism study (0.4% at 259 days. MRID 46840810).

Although cyproconazole is a triazole fungicide, the laboratory studies do not show formation of 1,2,4

- triazole and triazole conjugates ( i.e.

, triazole alanine and triazole acetic acid ) in soil or aquatic environments.

Cyproconazole’s degradates are detailed in Table 4

.Page 12 of 41 

### Table 4

. Cyproconazole and Its Environmental Transformation Products

Code Name/ Synonym Chemical Name Chemical Structure Study Type MRID System Maximum %AR (day) Final %AR (study length)

PARENT 

### Cyproconazole /
SAN 619F /

CGA 221949 IUPAC: (2RS,3RS;2RS,3SR)

- 2

- (4

- chlorophenyl)

- 3

- cyclopropyl

- 1

- (1H

1,2,4

- triazol

- 1

- yl)butan

- 2

- ol

CAS N ame : α

- (4

- chlorophenyl)

- α

- (1

- cyclopropylethyl)

- 1H

- 1,2,4

- triazole

- 1

- ethanol

CAS No.: 94361

- 06

- 5

Formula: C 15 H 18 ClN 3 O

MW: 291.8 g/mol
SMILES: CC(C1CC1)C(CN2C=NC=N2)(C3 =CC=C(C=C3)Cl)O
TRANSFORMATION PRODUCTS 

### Triazolyl
A lanine / (2

- amino

- 3

- (1

- H

- 1, 1, 2, 4

- triazol

- tyl)) propanoic acid NA NA Aerobic soil 41474401 Loamy sand 0

. 6 % ( 365 d) 0

. 6 % ( 365 d)



### Carbon D ioxide IUPAC: Carbon dioxide

Formula: CO 2 MW: 44 g/mol
SMILES: C(=O)=O C O O Aerobic soil 4684080 6 Sandy loam 7.9% ( 112 d) 1.9% ( 140 d)

Aerobic aquatic 46840810 River loam 0

. 4 % ( 259 d) 0

. 4 % ( 259 d)

Pond loam 0.4% ( 105 d) 0. 3 % (259 d)



### Unextracted
Residues

NA NA Aerobic soil 42534801 NC soil 36.3 % ( 210 d) 36.3 % ( 210 d)
46840805 Silt loam 55.7 % ( 300 d) 55.7 % ( 300 d)

4684080 6 Sandy loam 21.5 % ( 140 d) 21.5 % ( 140 d)

46840807 Sandy loam 11 % ( 84 d) 8.5% ( 140 d)

Aerobic aquatic 46840810 River loam 3.8 % ( 259 d) 3.8 % ( 259 d)
Pond loam 10 % ( 259 d) 10 % ( 259 d)Page 13 of 41 Code Name/ Synonym Chemical Name Chemical Structure Study Type MRID System Maximum %AR (day) Final %AR (study length)


### Unidentified [ 14 

### C] NA NA Aerobic soil 46840805 Silt loam 24.9 % ( 16 d) 16.5 % ( 300 d)

*NA = Not Available

### 14 

# 6. Receptors

Table 5 and Table 6 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 cyproconazole

. All of the submitted ecotoxicity data are pr esented
here ; however when more than one reliable study is available for the same endpoint, the more sensitive endpoint will be used for the registration review risk assessment.



## 6.1. Effects to Aquatic Organisms

On an acute exposure basis, cyproconazole is slightly toxic to freshwater and estuarine/marine fish as well as freshwater invertebrates (LC 50 

### s range from 19 to 26 mg/L). Cyproconazole is moderately toxic to estuarine/marine invertebrates.

Chronic toxicity data are available for freshwater fish and invertebrates only. In a fish early

- life
stage test (MRID 46950008)

, t he 59

- day post

- hatch toxicity of c yproconazole to r ainbow t rout was studied under flow

- through condit ions at concentrations up to 0. 305 m g a

. i

. /L

. The NOAEC
for wet weight was 0. 161 m g a

. i

. /L (based on a 16% reduction at the highest treatment level ) ; no other effects were observed

. In a 21

- day daphnid life cycle toxicity test (MRID 47036201), cyproconazole treatments up to 2.3 mg /L were studied under static

- renewal conditions. The
NOAEC based on a decrease in reproduction (approximately 20% reduction in live young/live adult) was 0.019 mg a

. i

. / L.

No chronic data are available for estuarine/marine fish or invertebrates. However, chronic NOAECs have been estimated for these taxa in previous assessments using the acute

- to

- chronic ratio (ACR) based on freshwater animal toxicity data as shown in Table 5

.

Aquatic plant toxicity data are available for one non

- vascular species, green algae , and one vascular species , duckweed

. Green algae was the most sensitive species tested with an EC 50 

### of
0.026 mg a.i./L and a NOAEC of 0.0059 mg a.i./L (MRI D 42656401).

Table 5

. Toxicity Endpoints for Aquatic Organisms Exposed to Cyproconazole

Taxonomic

Group Study Type Test
Substance

(% a.i.) Surrogate Species Toxicity Value

measured mg a.i./L (Acute Toxicity Category or Most Sensitive Endpoints ) MRID and Study
Classification

Aquatic Vertebrates

Freshwater
fish 1 Acute TGAI (96.2%) Rainbow Trout ( Oncorhynchus mykiss ) 96

- hr LC 50 = 19 (Slightly toxic) 40607733 Acceptable

TGAI (96.2%) Bluegill Sunfish ( Lepomis
macrochirus ) 96

- hr LC 50 = 21 (Slightly toxic) 40607734 Acceptable

21

- day TGAI (96.2%) Rainbow Trout 21

- d LC 50 = 3.2 ( Moderately toxic)

21

- d NOAEC = 0.65 (Loss of coordination) 41259301 Supplemental /

Quantitative

### 15 Taxonomic

Group Study Type Test
Substance

(% a.i.) Surrogate Species Toxicity Value

measured mg a.i./L (Acute Toxicity Category or Most Sensitive Endpoints ) MRID and Study
Classification

Chronic (Early

- l ife

Stage) TGAI (98.2%) Rainbow Trout 59

- d NOAEC/LOAEC =
0.161 / 0.305 (Wet weight) 46950008 Acceptable

Estuarine/
marine fish Acute TGAI (95.6%) Sheepshead Minnow ( Cyprinodon variegat u s ) 96

- hr LC 50 = 21 (Slightly toxic) 43187704 Acceptable

Chronic NA Sheepshead Minnow NOAEC = 0.178
Based on ACR 2 NA

Aquatic Invertebrates

Freshwater
invertebrates Acute TGAI (96.2%) Water Flea ( Daphnia magna ) 48

- hr EC 50 = 26 (Slightly toxic) 40607735 Acceptable

Chronic TGAI (98.2%) Water Flea 21

- d NOAEC/LOAEC =
0.019 / 0.073 ( Reproduction ) 47036201 Supplemental /

Quantitative

TGAI (>95%) Water Flea 21

- d NOAEC/LOAEC =
0.29 / 0.57 (Reproduction) 43187701 Acceptable

Estuarine/

marine
invertebrates Acute (Shell Deposition) TGAI (95.26) Eastern Oyster ( Crassostrea

virginica ) 96

- hr EC 50 = 2.6 (Moderately toxic) 43187702 Acceptable

Acute TGAI (95.6%) Mysid Shrimp ( Mysidopsis bahia ) 96

- hr LC 50 = 9.6 (Moderately toxic) 43187703 Acceptable

Chronic NA Mysid Shrimp NOAEC = 0. 007
Based on ACR 3 NA

Aquatic Plants

Aquatic plants and algae Vascular TGAI (98.2%) Duckweed ( Lemna gibba ) EC 50 = 0.094

7

- d NOAEC/LOAEC =
0.0245 / 0.0457 (Frond number) 47067101 Acceptable

Non

vascular TGAI (95.8%) Green Algae ( Pseudokirchneriella subcapitata ) EC 50 = 0.0 26

5

- d NOAEC/LOAEC =
0.0 059 / 0.011 (Cell density) 42656401 Acceptable

TGAI = Technical Grade Active Ingredient; NA = Not Applicable

1 Freshwater fish are surrogates for aquatic

- phase amphibians

. 2 ACR = Rainbow trout 96

- hour LC 50 / Rainbow trout NOAEC = 19 m g/L / 0. 161 m g/L = 118

Estimated sheepshead minnow NOAEC = Sheepshead minnow 96

- hour LC 50 / ACR = 21 mg/L / 118 = 0. 178

m g/L

3 ACR = Daphnia magna 48

- hour LC 50 / Daphnia magna NOAEC = 26 m g/L / 0.0 19 m g/L = 1368

Estimated mysid shrimp NOAEC = mysid shrimp 96

- hour LC 50 / ACR = 9

. 6 m g/L / 1368 = 0.00 7 m g/L



## 6.2. Effects to Terrestrial Organisms

Available acute oral and dietary toxicity data suggest that cyproconazo le is moderately toxic to birds, slightly to moderately toxic to mammals , and practically non

- toxic to honey bees.

### 16 Two avian reproduction studies on mallard ducks (MRID s 43287701

, 47340801 ) showed effects on multiple reproduct ive endpoints including l ive embryos/viable embryos, n ormal hatchlings/eggs set, n ormal hatchlings/li ve embryos, and h atching survival/eggs set . The most sensitive endpoint identified was live 3

- week embryos/viable embryos, which was reduced at 10.9 mg a.i ./kg

- diet (NOAEC = 7.3 mg a.i./kg

- diet ; MRID 47340801 ). In a bobwhite quail study (MRID 43347001) , significant reproductive effects on e ggs laid, eggs set, viable embryos, live
21

- day normal embryos, normal hatchlings, 14

- day survivors and several growth e ffects
occurred at 250 mg a.i./kg

- diet (NOAEC = 50 mg a.i./kg

- diet )

. A two

- generation rat reproduction study ( MRID 406 0 7723) determined a NOAEC of 120 mg a.i./kg

- diet ( 8

. 29 mg a.i. /kg

- bw/ day) for mammalian reproductive effects. No chronic data are available for honey
bees.

For terrestrial plants, vegetative vigor and seedling emergence studies were conducted on corn ( Zea mays ), onion ( Allium cepa ), wheat ( Triticum aestivum ), bean ( P h aseolus vulgaris ), carrot ( Daucus carota ), l ettuce ( Lactuca sativa ), soybean ( Glycine max ), ryegrass ( Lolium perenne ), cabbage ( Brassica oleracea ), lettuce ( Lactuca sativa ), and tomato ( Lycopersicon esculentum ). Tier 2 seedling emergence studies were conducted on ryegrass, cabbage, lettuce, and toma to (MRID 46218512 ) . Tier 2 vegetative vigor studies were conducted on wheat, bean, cabbage, lettuce, soybean, and tomato (MRID 46218511) . The remaining species were tested using Tier 1 studies. Dicots were more sensitive than monocots and fresh and dry wei ght were the most sensitive endpoints in both studies. Cabbage was the most sensitive species tested, with an IC 25 

### of 0.066 lbs a.i./A and a NOAEC of 0.091 lbs a.i./A based on wet weight in the seedling emergence study.

Table 6

. Toxicity Endpoints for Terrestrial Organisms Exposed to Cyproconazole

Taxonomic

Group Study Type Test
Substance

(% a.i.) Surrogate Species Toxicity Value
measured a.i. (Acute Toxicity Categor y or Most Sensitive Endpoints ) MRID and Study
Classification

Birds 1 Acute Oral TGAI (95.6%) Bobwhite quail ( Colinus virginianus ) LD 50 = 150 mg/kg

- bw (Moderately toxic) 40607730 Acceptable

Sub

- acute

D ietary TGAI (95.6%) Bobwhite quail LC 50 = 816 mg/kg

- diet (Moderately toxic) 40607731 Acceptable

TGAI (95.6%) Mallard duck ( Anas platyrhynchus ) LC 50 = 1197 mg/kg

- diet (Slightly toxic) 40607732 Acceptable

Chronic TGAI (95.6%) Bobwhite quail NOAEC/LOAEC = 50 / 250 mg/kg

- diet ( Eggs laid, eggs set, viable embryos, live 21

- day normal embryos, normal hatchlings,

14

- day survivors, hatchling wt., 14

- day survivor wt., food consumption, female body wt. ) 43347001 Acceptable

TGAI (95.6%) Mallard duck NOAEC/LOAEC = 10 / 50 mg/kg

- diet ( Live embryos/viable embryos,

Normal hatchlings/eggs set,

Normal hatchlings/live

embryos, Hatching survival/eggs set ) 43287701 Acceptable

### 17 Taxonomic

Group Study Type Test
Substance

(% a.i.) Surrogate Species Toxicity Value
measured a.i. (Acute Toxicity Categor y or Most Sensitive Endpoints ) MRID and Study
Classification

TGAI (96.0%) Mallard duck NOAEC/LOAEC = 7.3 / 10.9 mg/kg

- diet ( Live embryos/viable embryos ) 47340801 Supplemental /

Quantitative

Mammals 2 Acute Oral TGAI Laboratory rat ( Rattus norvegicus ) LD 50 = 1020 mg/kg

- bw (Slightly toxic) 40607712 Acceptable

TGAI Mouse ( Mus musculus ) LD 50 = 270 mg/kg

- bw (Moderately toxic) 46840822 Acceptable

Acute
Inhalation TGAI Laboratory rat 4

- hr LC 50 >5.6 mg/L 40607715 Acceptable

Chronic (2

- generation

R eproduction) TGAI (95.6%) Laboratory rat NOAEC = 120 mg/kg

- diet
NOAEL = 8.29 mg/kg bw/day (No effects) 40607723 Acceptable

Terrestrial
Invertebrates Acute C ontact TGAI (95.6%) Honey bee ( Apis mellifera ) LD 50 >100 μg/bee (Practically non

- toxic) 41125601 Acceptable

TEP (40%) Honey bee LD 50 >100 μg/bee (Practically non

- toxic) 41125602 Acceptable

Acute Oral TGAI (95.6%) Honey bee LD 50 >1000 μg/bee (Practically non

- toxic) 41125601 Acceptable

TEP (40%) Honey bee LD 50 >50 μg/bee (Practically non

- toxic) 41125602 Acceptable

Terrestrial

Plants Seedling Emergence TEP (30.6%) Monocot: Onion IC 25 > 0.58 lbs /A
NOAEC = 0.58 lbs /A (D ry weight ) 46218512 Acceptable Dicot: Cabbage IC 25 = 0.091 lbs /A
NOAEC = 0.066 lbs /A (Fresh weight )

Vegetative

Vigor TEP (30.6%) Monocot: Ryegrass IC 25 > 0.58 lbs /A
NOAEC = 0.58 lbs /A (D ry weight ) 4621851 1 Acceptable
Dicot: Cabbage IC 25 = 0.50 lbs /A
NOAEC = 0.090 lbs /A (D ry weight )

1 Birds are surrogates for terrestrial

- phase amphibians and reptiles.

2 Mammalian toxicity endpoints are provided and reviewed by the U.S. EPA Office of Pesticide Programs Health
Effects Division (HED).



## 6.3. Ecological Incidents

The ecological incident information system (EIIS) is an OPP database that houses ecological
incidents that ha ve 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 suspected of contributing to the incident, and results of any chemical residue analysis or other analy ses conducted during incident investigation. EIIS incidents are categorized according to the certainty that the incident resulted from pest icide exposure. The Avian Monitoring System (AIMS) is a database administered by the American Bird Conservancy that

c ontains publicly available data on reported avian i ncidents involving pesticides. Many of the
incidents listed in this database are also in the EIIS. Additionally, the U.S. EPA Office of Pesticide Progr ams Incident Data System (IDS) compiles aggregate inci dents reported to the

### 18 agency. These reports do not include detailed information about the incidents. An absence of reports does not necessarily equate to an absence of incidents given the nature of incident reporting.

As o f July 22, 2015, no incidents wer e reported for cyproconazole in EIIS, AIMS, or IDS.



# 7. Exposure Pathways of Concern

The environmental fate properties and use patterns of cyproconazole indicate that direct spray, spray drift, leaching, and runoff represent potential transport mechanisms to aqu atic and terrestrial organisms. Drinking water and inhalation exposure pathways were screened using the SIP (Screening Imbibition Pro gram) and STIR (Screening Tool for Inhalation Risk) screening
methods . SIP results indicated that drinking water alone is a potential acute and chronic exposure pathway of concern for birds and mammals (see Appendix A ). STIR results showed t hat vapor and droplet inhalation are not likely to be exposure pathway s of concern for bir ds or mammals (see Appendix B ). SIP an d STIR are described in detail

at: http://www.epa.gov/oppefed1/models/terrestrial/index.htm

.



# 8. Analysis Plan

8.1. Stressors of Concern

Ecological Ris k Assessment

Cyproconazole is the stressor of concern for the ecological risk assessment. There are no major degradates of cyproconazole identified in the reviewed environmental fate studies.

Drinking Water Assessment

An updated drinking water assessment will be conducted to support future human health dietary
risk assessments of cyproconazole

. Cyproconazole alone is the stressor of concern for drinking water as there are no identified major degradates.



## 8.2. Measures of Exp osure

EFED will use standard available models to evaluate potential exposures to aquatic and terrestrial organisms as described at http://www.epa.gov/ oppefed1/models/water/index.htm
and http://www.epa.gov/pesticides/science/models_db.htm

. T he Surface Water Concentration Calculator (SWCC) is currently the model typically use d to estimate aquatic exposure. T

- REX and TerrPlant are currently models typically used to estimate terrestrial exposure.

On the USGS NAWQA surface and ground water database ( http://cida.usgs.gov/nawqa_queries_public/ ), cyproconazole wa s monitored from June 2010 to September 2013 in 13 states (California, Georgia, Iowa, Illinois, Indiana, Kansas, Kentucky,

### 19 Minnesota, Missouri, Nebraska, Ohio, South Dakota, Wisconsin). C yprocona zole was not detected at the detection limit of 4.7 ng/L in surface water and 1.0 μg/kg in sediment samples.

Data from USEPA STORET Data Warehouse ( http://www.epa.gov/storet/ ) shows that cyproconazole was monito red in surface water on six sampling stations in the State of California, Marin and San Mateo County from February to July 2006 (18 samples total) . The only detection was in San Mateo County on February 2006 at 0.028 μg /L.



### In the state of California, c yproconazole was not detected in surface water and sediment samples reported in the California Department of Pesticide Regulation ( CDPR) surface water database ( http://www.cdpr.ca.gov/do cs/emon/surfwtr/surfcont.htm )

.



## 8.3. Measures of Effect

T he most sensitive of the t oxicity data presented in Section 6 of this problem formulation will be used to calculate risk quotients. Any additional information subm itted by the registrant or found in the open literature prior to con duct of the risk assessment will also be considered. The open literature studies are identified using EPA’s ECOTOXicology database ( ECOTOX) (USEPA,
2007 a ), 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 communi ties from loss of species that are sensitive to the chemicals and from changes in structure and functional
characteristics of the affected communities.



## 8.4. Endangered Species Assessments

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 Approaches developed to implement the recommendations of the April 2013 National Aca demy of Sciences (NAS) report, Assessing Risks to Endangered and Threatened Species from Pesticides

. The NAS report outlines recommendations on specific scientific and technical issues related to the development of pesticide risk assessments that EPA and the Services must conduct in connection with their obliga tions under the ESA and FIFRA. EPA will address concerns specific to cyproconazole in connection with the development of its final regist ration review decision for cyproconazole

.

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 scientific
differences be tween the EPA and the Services. Details of the joint Interim Approaches are contained in the November 1, 201 3 white paper

, Interim Approaches for National

- Level Pesticide Endangered Species Act Assessments Based on the Recommendations of the National Academy of Sciences April 2013 Report.

### 20 Given that the agencies are continuing to develop and work toward implementation of the Interim Approaches to assess the potential risks of pesticides to lis ted species and their designated critical habitat, this ecological problem formulation supporting the Preliminary Work
Plan for cyproconazole does not describe the specific ESA analysis, including effects determinations for specific listed species or desig nated critical habitat, to be conduct ed during registration review. While the agencies continue to develop a common method for ESA analysis, the planned risk assessment for the registration review of cyproconazole will describe the level of ESA analysis co mpleted 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 have 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 cyproconazole a s part of completing this registration review.



## 8.5. Endocrine Disruptor Screening Program

Cyproconazole was not included in the first group of 67 chemicals issued an orde r to conduct Tier 1 EDSP testing

. For additional information the EDSP program,
visit http://www.epa.gov/endo/

.



# 9. Preliminary Identification of Data Gaps

9.1. Environmental Fate

Table 7 identifies 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.

Table 7 . Submitted Environmental Fate Data for Cyproconaz ole

OCSPP
Guideline Data Requirement Submitted
Studies (MRID) Study
Classifications Are Additional
Data Needed to
Conduct Risk
Assessment? Current Additional Data
Need /Comments

835.2120 Hydrolysis 40607706 Acceptable No None 46840804 Acceptable No

835.2240 Aqueous photolysis 40607707 Acceptable No None

835.2410 Soil photolysis 40607707 Acceptable No None

### 21 OCSPP
Guideline Data Requirement Submitted
Studies (MRID) Study
Classifications Are Additional
Data Needed to
Conduct Risk
Assessment? Current Additional Data
Need /Comments

835.4100 Aerobic soil
metabolism 46840805 Supplemental No

None 46840806 Supplemental No

41474401 Acceptable No

42534801 Supplemental No

46840807 Supplemental No Values from these studies are ancillary and cannot be used
for risk assessment. 46840808 Supplemental No

46840809 Supplemental No

835.4200 Anaerobic soil
metabolism No Data Not Applicable No None. Data from anaerobic aquatic metabolism will be
used in lieu of anaerobic soil
in risk assessment.

835.4300 Aerobic aquatic
metabolism 46840810 Acceptable No None

835.4400 Anaerobic aquatic
metabolism 43683201 Acceptable No None

835.1230
835.1240 Adsorption/ desorption and leaching 40607709 Acceptable No
None 41441301 Acceptable No

835.6100 Terrestrial field dissipation 40607710 Supplemental No

None 41384102 Supplemental No

41800701 Supplemental No

41800702 Supplemental No

41384105 Acceptable No

42430701 Acceptable No

42430702 Acceptable No

850.1730 Fish bioconcentration 40624302 Acceptable No

None 4062430 3 Acceptable No

41220801 Acceptable No

850.6100 Analytical method in
soil No Data Not Applicable Yes An environmental chemistry
method and independent laboratory validation to detect cyproconazole in soil

are needed

.

Analytical method in

water No Data Not Applicable Yes An environmental chemistry
method and independent laboratory validation to detect cyproconazole in

water are needed

.



## 9.2. Effects

Table 8 and Table 9 identif y 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. Rationale for the additional non

- guideline data requested is presented below the tables.

### 22 Table 8

. Submitted Aquatic Ecological Effects Data for Cyproconazole

OCSPP
Guideline Data Requirement Submitted
Studies (MRID) Study
Classifications Are Additional
Data Needed to
Conduct Risk
Assessment? Current Additional Data
Need

850.1010 Freshwater
invertebrate acute toxicity 40607735 Acceptable No None

850.1025
850.1035
850.1045
850.1055 Saltwater
invertebrate acute toxicity 43187702 Acceptable

No None
43187703 Acceptable

850.1075 Freshwater fish acute toxicity 40607733 Acceptable No None 40607734 Acceptable

850.1075 Saltwater fish acute toxicity 43187704 Acceptable No None

850.1300 Freshwater
invertebrate

life cycle 47036201 Supplemental No None 43187701 Acceptable

850.1350 Saltwater
invertebrates

life cycle None NA Yes A chronic study on
estuarine/marine
invertebrates is needed to reduce uncertainty resulting from potential chronic exposure in saltwater
environments. Cyproconazole has been shown to impair reproduction in freshwater

invertebrates (MRID s 47036201 and 43187701).
ACRs will be used in the
absence of data.

850.1400 Freshwater fish early

- life stage 46950008 Acceptable No None

### 23 OCSPP
Guideline Data Requirement Submitted
Studies (MRID) Study
Classifications Are Additional
Data Needed to
Conduct Risk
Assessment? Current Additional Data
Need

850.1400 Saltwater fish early

- life stage None NA No A chronic study on
estuarine/marine fish would reduce uncertainty resulting from potential chronic exposure in saltwater
environments. However,
chronic data for freshwater
fish indicate that saltwater
fish would need to be two orders of magnitude more

sensitive (at current use rates) to result in a risk
concern. An ACR will
continue to be used in the
absence of data.

850.1500 Fish life cycle None NA No None

850.1735 Whole sediment
freshwater
invertebrate None NA No Kow, Koc, and Kd triggers for requesting sediment
studies are not met for cyproconazole. 850.1740 Whole sediment
estuarine/marine

invertebrate None NA No

850.4400 Aquatic plant Toxicity Test using Lemna spp. 47067101 Acceptable No None

850.4500 Algal toxicity 42656401 Acceptable Yes Studies with two additional species will reduce uncertainty in the
assessment of risk to non

vascular plants . Suggested species are the freshwater
diatom Navicula pelliculosa and the marine
diatom Skeletonema

costatum

.

850.4550 Cyanobacteria None NA Yes A cyanobacteria will reduce uncertainty in the
assessment of risk to non

vascular plants.

### 24 Table 9

. Submitted Terrestrial Ecological Effects Data for Cyproconazole

OCSPP
Guideline Data Requirement Submitted
Studies (MRID) Study
Classifications Are Additional
Data Needed to
Conduct Risk
Assessment? Current Additional Data
Need

850.2100 Avian oral toxicity 40607730 Acceptable Yes A study with a passerine species will reduce uncertainty in the
assessment of risk to birds.

850.2200 Avian dietary toxicity 40607731 Acceptable No None 40607732 Acceptable

850.2300 Avian reproduction 43347001 Acceptable

No None 43287701 Acceptable

47340801 Supplemental

Non

guideline Avian inhalation None NA No None. Not a potential exposure pathway of

concern for birds.

850.3020 Honey bee acute contact toxicity 41125601 Acceptable No None 41125602 Acceptable

850.3030 Honey bee residue on foliage None NA No None. Acute contact toxicity endpoint is >11 μg/bee.

850.3040 Field testing for pollinators (Tier III) None NA Yes See justification tables
below for additional
details.

Non

guideline

(Tier I) Honey bee adult acute oral toxicity 41125601 Acceptable
No None 41125602 Acceptable

Non

guideline

(Tier I) Honey bee larvae

acute toxicity None NA Yes A larvae acute study will reduce uncertainty in the
risk assessment for

pollinators. See justification tables below

for additional details.

Non

guideline

(Tier I) Honey bee adult chronic 10d toxicity None NA Yes An adult chronic oral study will reduce uncertainty in

the risk assessment for pollinators. See justification tables below

for additional details.

Non

guideline

(Tier I) Honey bee larvae chronic toxicity None NA Yes A larvae chronic study will reduce uncertainty in the
risk assessment for

pollinators. See justification tables below

for additional details.

### 25 OCSPP
Guideline Data Requirement Submitted
Studies (MRID) Study
Classifications Are Additional
Data Needed to
Conduct Risk
Assessment? Current Additional Data
Need

Non

guideline (Tier II) Semi

- field testing for pollinators (tunnel or colony feeding studies) None NA Yes See justification tables
below for additional
details.

Non

guideline (Tier II) Field trial of residues in pollen
and nectar None NA Yes See justification tables
below for additional
details.

850.4100 Seedling Emergence 46218512 Acceptable No None

850.4150 Vegetative Vigor 4621851 1 Acceptable No None



### Study Title: Pollinator Acute Oral Toxicity, Larvae Rationale for Requiring the Data Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use settings. 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 ex posed. Therefore, potential adverse effects to developing bees and other insect pollinators could result from exposure to pesticide residues. Available toxicity studies do not address possible effects on brood (larvae and pupae) survival/development.

Becau se 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 bee brood.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for terrestrial invertebrates using the honeybee as a surrogate test species. The guidance discusses Tier I laboratory

- based acute toxicity studies of individual honeybee 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 found at: http://www2.epa.gov/pollinator

- protection/pollinator

- risk

- assessment

guidance . Additional guidance on larval honeybee toxicity test design can be found in OECD Test

Guideline 237 http://www.oecd

- ilibrary.org/environment/test

- no

- 237

- honey

- bee

- apis

- mellifera

- larval

toxicity

- test

- single

- exposure_9789264203723

- en

. Practical Utility of the Data

How will the data be used? The Tier I acute oral toxicity d ata on honeybee larvae serve as a foundation for the screening

- level assessment of potential risk to non

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

- listed terrestrial invertebrate insec ts, including pollinators, and/or modify their designated critical habitat from acute 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 under standing of the potential effects on terrestrial species and whether there is a differential sensitivity of larval bees relative to adult bees. If acute oral effects data for larvae are not available, risks to terrestrial insects from acute oral exposure w ill 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

### 26 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.

Study Title: Pollinator Chronic Oral Toxicity, Adult Rationale for Requiring the Data Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use settings. Pesticide 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 honeybees and other pollinators from oral exposure to some pesticides could exist. Currently available toxicity studies do not address possible
lethal and suble thal 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 p esticide residues, and subsequently brought back to the hive, it is important to determine the chronic oral toxicity of this compound to adult honeybees and other pollinators.

The Office of Pesticide Programs has made available a guidance regarding ecolog ical testing for invertebrates with the honeybee. The guidance discusses Tier I laboratory

- based chronic oral toxicity studies of individual adult honeybees as a critical component of the screening

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

- protection/pollinator

- risk

- assessment

- guidance . Study design elem ents
for the chronic 10

- day oral toxicity test with honeybees are similar to the OECD Test Guideline 213 acute oral toxicity test http://www.oecd

- ilibrary.org/environment/test

- no

- 213

- honeybees

- acute

- oral

toxicity

- test_9789264070165

- en

. Practical Utility of the Data

How will the data be used? The Tier I chronic oral toxicity 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 invertebrate insects, including pollinators, from chronic 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 broad range of terrestrial species, particularly insect p ollinators and to determine whether adult toxicity differs substantially from other life stages evaluated in other Tier I tests. If chronic oral effects data for adults are not available, risks to terrestrial insects from chronic oral exposure will be assu med.

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.

Study Title: Pollinator Chronic Oral Toxicity, Larvae Rationale for Requiring the Data Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use settings. 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 ex posed. Therefore, potential effects to developing bees could result from chronic oral exposure to pesticide residues. Available toxicity studies do not

### 27 address possible chronic effects on brood (larvae and pupae) survival. Because of the potential for poll en 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 information on whethe r honeybee larvae differ in sensitivity from adult bees following chronic exposure.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for invertebrates with the honeybee. The guidance discusses Tier 1 laboratory

- based chronic oral toxicity studies of individual honeybee 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 found at: http://www2.epa.gov/pollinator

- protection/pollinator

- risk

- assessment

- guidance

. Additional information on larval honeybee toxicity repeat exposure test design can be found in the
OECD draf t guidance http://www.oecd.org/env/ehs/testing/Draft_GD_honeybees_rep_exp_for_2nd_CR_25_November_201 3.pdf

. Practical Utility of the Data

How will the data be used? The Tier I chronic oral 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 inv ertebrate insects, including pollinators, from chronic 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 direc t 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
relative to adul ts. If chronic oral effects data for larvae are not available, risks to terrestrial insects from chronic oral 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.

Study Title: Pollinator Tier II Semi

- Field Toxicity Testing (tunnel/enclosure studies) Rationale for Requiring the Data Tier II 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. Pesticide residues may be transferred to pollen and/or nectar of treated plants and subsequently brought back to t he hive and may adversely affect developing brood (egg, larvae, and pupae) and adult bees . Screening

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

- level. Because of the potenti al for pollen and nectar to be contaminated 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 stu dy. In addition to providing effects data, these studies can provide data on exposure as pesticide residues in pollen/nectar of treated plants.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for

### 28 invertebrates w ith the honeybee. The guidance describes the tiered testing process and can be found at: http://www2.epa.gov/pollinator

- protection/pollinator

- risk

- assessment

- guid ance . Additional information on honeybee colony studies under semi

- field conditions can be found in the OECD Guidance 75 http://www. oecd.org/officialdocuments/publicdisplaydocumentpdf/?cote=env/jm/mono%28

. Practical Utility of the Data

How will the data be used? Tier II 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 I) laboratory

- based studies of individual bees are evident in colony

- level studies
under semi

- field conditions. The Tier II semi

- field te st 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 insect 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 i nvertebrates. Measured residues in pollen/nectar can also be
used 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 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 speci es 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.

Study Title: Pollinator Tier II Semi

- Field Toxicity Testing (feeding studies) Rationale for Requiring the Data 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 II 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 terrestria l invertebrates based on Tier I studies of individual bees. Feeding studies utilize 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 forage 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 fro m Tier II 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. 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 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 Pesticide Programs has made available a guidance regarding ecological testing for invertebrates with the honeybee. The guidance describes the tiered testing process and can be found at: http://www2.epa.gov/pollinator

- protection/pollinator

- risk

- assessment

- guidance

. Additional information

### 29 on honeybee colony feeding studies can be found in the EPPO Guidance 170 at: http://www.nationalbeeunit.com/index.cfm?pageId=187

.

Practical Utility of the Data

How will the data be used? Tier II 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 II tunnel studies. The study will be used to determine whether potential adverse effects to insect pollinators at the whole colony level when bees are able to forage natural ly 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 I studies 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?
Tier II colony

- level data will be used to refine screening

- level risk estimates derived using Tier I laboratory

- based data on individual bees. The Tier II 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 threatened or endangered species or their designated critical habitat. Without these data, EPA may need to presume
risk wh ich will limit the flexibility of pesticide products to comply with FIFRA and the ESA, and could result in significant use restrictions.

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

qu antification of pollinator

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

- to

- hive parts of treated trees and plants, including (where appropriate), but not limited to, guttation water, sap/resins, 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 residue data for crops and application methods of concern.

The Office of Pesticide Programs has made available a gu idance regarding ecological testing for invertebrates with the honeybee. The guidance can be found at: http://www2.epa.gov/pollinator

protection/pollinator

- risk

- a ssessment

- guidance

. Practical Utility of the Data

### 30 How will the data be used?

Measured residue d ata will be used to refine conservative estimates of pesticide exposure and reduce uncertainties associated with the Tier I 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 Age ncy’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 aff ect federally listed threatened or endangered species or their designated critical habitat. Without these data, EPA will have to rely on conservative estimates of exposure which will limit the flexibility of pesticide products to comply with FIFRA and the ESA, and could result in use
restrictions.



# 10. References

Gardner, D. S. , B. E. Branham, and D. W

. Lickfeldt

. 200 0

. Effects of turfgrass on soil mobility and dissipation of cyproconazole

. Crop Sci

. 40 : 1333

– 1339

.

Harvey, Brian. 2004. Cyproconazole. Document M

- II, Section 5. From Section 18 reuqest submitted by Syngenta (Ruhi Rezaaiyan) on April 28, 2005 to Dan Rosenblatt (USEPA).

HSDB. 1995. BioByte; ClogP for Windows Program. BioByte Corp., Claremont, CA (1995). http://toxnet.nlm.nih.gov/cgi

- bin/sis/search/r?dbs+hsdb:@term+@rn+@rel+94361

- 06

- 5



### Payne

, A

. H . and D.B. Hales. 2004. Overview of steroidogenic enzymes in the pathway from
cholesterol to active steroid hormones. Endocr Rev. 25 :947

– 970.

USEPA. 2005. Syslo, S. Request for Registration of New Use of Cyproconazole on Greenhouse

Roses. U.S. Environmental Protection Agency, Office of Pesticide Programs,
Environmental Fate and Effects Division. Memorandum to the Registration Division. DP Barcodes 313858, 313859, dated 11/29/05.

USEPA. 2006a. 1,2,4

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

- derivative Fungicide Compounds. Office of Pesticide Programs Environm ental 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 Aggregate Risk A ssessment 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.

### 31 USEPA . 2007. Hetrick, J

. Tier I Drinking Water Assessment for Cyproconazole . U.S. Environmental Protection Agency, Office of Pesticide Programs, Environmental Fate and Effects Division. Memorandum to the Registration Division and Health Effects Division

. DP Bar code 343771 , dated 9/1 1 /07.

USEPA. 2007 a . ECOTOXicology Database. Office of Research and Development National Health and Environmental Effects Research Laboratory’s (NHEERL’s) Mid

- Continent Ecology Division (MED). http://cfpub.epa.gov/ecotox/

USEPA. 2007b. Flaherty, C. and J. Hetrick. New Use Registration: Ecological Risk Assessment for Cyproconazole on Cereals, Corn, and Soybeans. U.S. Environmental Protection Agency, Office of Pesticide Programs, Environmenta l Fate and Effects Division. Memorandum to the Registration Division. DP Barcode 330276 , dated 9/12/07.

USEPA . 2010. Stevenson, C. and C. Sutton. Ecological Risk Assessment in Support of the Prothioconazole Section 3 New Use on Crop Groups 15 and 16 (Cere al Grains and Forage, Fodder and Straw of the Cereal Grains Group except Sweet Corn, Sorghum and Rice) and Sweet Corn. U.S. Environmental Protection Agency, Office of Pesticide Programs, Environmental Fate and Effects Division. Memorandum to the Registrati on Division. DP Barcode 363044, dated 2/16/10.

USEPA. 2011. Judkins, D. and R. David Jones. Cyproconazole : Ecological Risk Assessment to Support Proposed New Use on Turf (Golf Course and Sod farm) and Ongoing Use on Field Grown Rose Bushes. U.S. Environmental Protection Agency, Office of Pesticide Programs, Environmental Fate and Effects Division. Memorandum to the Registration
Division. DP Barcode 381967, dated 4/28/11.

USEPA. 2012. Judkins, D. and R. David Jones. EFED Screening Ecological Risk Assessment for
the Proposed New Use of Cyproconazole on Peanuts ( Submission 911090 ) . U.S. Environmental Protection Agency, Office of Pesticide P rograms, Environmental Fate and
Effects Division. Memorandum to the Registration Division. DP Barcode 403335, dated
11/1/12.

USEPA

. 2014. Judkins, D. and K. Garber. Cyproconazole : Refinement to Avian Reproduction
Risk Assessment to Support Proposed New Us e on Turf. U.S. Environmental Protection Agency, Office of Pesticide Programs, Environmental Fate and Effects Division.

M emorandum to the Registration Division. DP Barcode 410944, dated 1/8/14.

USEPA. 2015 a . Cyproconazole Screening Level Usage Analysis (S LUA). U.S. Environmental Protection Agency, Office of Pesticide Programs, Biological and Economic Analysis
Division. Dated 4/10/15.

USEP A. 2015 b

. Risk Assessment of New use of Cyproconazole for the Protection of Engineered and Composite Wood Products . D P Barcode 428952 , dated 9/9/15

.

USEPA, PMRA, and CDPR. 2014. Guidance for Assessing Pesticide Risks to Bees. Office of Pesticide Programs, USEPA, Washington D.C. Health Canada Pest Management

### 32 Regulatory Agency, Ottawa, ON, Canada. California Department of Pesticide Regulation, Sacramento, CA. June 23, 2014.

White, T.C., K.A. Marr, and R.A. Bowden. 1998. Clinical, cellular, and molecular factors that contribute to antifungal drug resistance. Clin Microbiol Rev

. 11 :382

– 402.



## 10.1. Submitted Environmental Fate Studies

MRID Citation

40607706 Wission, M. (1987) Hydrostability in Aqueous Buffer Solutions of pH 1,5,7 and 9 in 1 N Hydrochloric Acid and 1 N Sodium Hydroxide at 50 (degrees)C + 80 (degrees)C: Report No. 11692/86. Unpublished study prepared by Sandoz Ltd. 18 p.
46840804 Glanzel, A. (1999) Hydrolysis of (Carbon 14) Triazole Labelled SAN 619 F under Laboratory Conditions: Cyproconazole: Final Report. Project Number: 99AG04, T001920/06. Unpublished study prepared by Novartis Crop Protection, AG. 58 p.
40607707 Skinner, W.; Jamieson, G.; Quistad, G. (1985) Photodegradation of SAN 619F: Report No. 3760

- 24

- 09

- 85. Unpublished study prepared by Zoecon Corp. 20 p.

41474401 Tong, T.; Krueger, J. (1990) Aerobic Soil Metabolism of SAN 619F (Cyproconazole): Lab Project
Number: 433015

- 5. Unpublished study prepared by Sandoz Crop Protection Corp. 111 p.

42534801

40607708 Wisson, M. (1992) Carbon 14 Benzyl

- Cyproconazole = ?carbon 14|

- Benzyl

-- SAN 619 F: Aerobic Degradation in Three Types of Soil (Balance Study): Final Report: Lab Project Number: BS3175: 41'321. Unpublished study prepared by Sandoz Agro Ltd. 53 p. Skinner, W.; Quistad, G.; Sakai, D. (1986) Aerobic Soil Metabolism of SAN 619F: Report No. 3760

- 24

- 08

- 85. Unpublished study pre

- pared by Sandoz Crop Protection Corp. 19 p.
46840805 Kuet, S. (2006) Cyproconazole: Rate of Degradation of (Carbon 14)

- Triazolyl Labelled Cyproconazole in One US Soil, at Different Concentrations, Under Aerobic Laboratory Conditions at 20 Degrees Celsius: Final Report Amendme nt. Project Number: T019910/04. Unpublished study prepared by Jealott's Hill Res. Station. 78 p.
46840806 Wisson, M. (1994) [U

- (Carbon 14)

- Phenyl]

- Cyproconazole Laboratory Soil Metabolism Study: Final Report. Project Number: 41322, BS4506, T001916/06. Unp ublished study prepared by Sandoz Ltd. Agrochemicals. 53 p.
46840807 Wisson, M. (1989) Laboratory Metabolism Study in a Field Soil: Cyproconazole: Final Report. Project Number: 41309, T001913/06. Unpublished study prepared by Sandoz Ltd. Agrochemicals. 29 p.

46840808 Wisson, M. (1990) Degradation in Three Types of Soil Under Various Conditions (Laboratory Study with Field Soils): Cyproconazole: Final Report. Project Number: 41313, T001914/06. Unpublished study prepared by Sandoz Ltd. Agrochemicals. 45 p.
46840809 Tong, T. (1990) Preliminary Study of Aerobic Soil Metabolism of 14

- Carbon

- SAN 619F on Cook County Clay Loam at 0.1 ppm Concentration: Cyproconazole: Final Report. Project Number: 300197, T001907/06. Unpublished study prepared by Sandoz Ltd. Agroc hemicals. 16 p.
43683201 Blumhorst, M. (1995) Anaerobic Aquatic Metabolism of (Carbon

- 14)

- Cyproconazole: Lab Project Number: 111S16: 111P09: DP 301677. Unpublished study prepared by EPL Bio

- Analytical Services, Inc. 301 p.
46840810 Volkel, W. (1997) [U

- (Carbon 14)

- Triazolyl]

- Cyproconazole: Route and Rate of Degradation in Aerobic Aquatic Systems: Final Report. Project Number: 613001, T001917/06. Unpublished study prepared by RCC Umweltchemie Ag. 75 p.
40607709 Skinner, W.; Collier, K.; Quistad, G. (1 985) Adsorption, Desorption and Mobility of SAN 619F in Soil: Report No. 3760

- 24

- 11

- 85. Un

- published study prepared by Zoecon Corp. 26 p.

41441301 Tong, T. (1990) Equilibrium Study for Soil Adsorption/desorption of SAN 619F: Lab Project Number:
3760

- 24

- 1 1

- 85. Unpublished study prepared by Sandoz Crop Protection Corp. 15 p.

40607710 Cahill, W.; Bade, T. (1988) Dissipation of Cyproconazole in a Cali

- fornia Soil: Project No. 433018: Report 2. Unpublished study prepared by Sandoz Crop Protection Corp. 92 p.

### 33 41384102 Ali, S. (1990) Dissipation and Mobility of Cyproconazole in Soil after Four Applications to Turfgrass in Maryland: Lab Project Number: 433018; Report No. 3. Unpublished study prepared by Sandoz Crop Protection Corp. 252 p.
41384105 Ali, S. (1990) Storage Stability of Cyproconazole in Soil: Lab Project Number: 433018; Report No. 6. Unpublished study pre

- pared by Sandoz Crop Protection Corp. 24 p.

41800701

40624301

41384101

41461501 Ali, S. (1991) Interim Report on Dissipation and Mobil ity of Cypro

- conazole in Soil after Four Applications to Bare Ground in Ore

- gon: Lab Project Number: 433018: 11. Unpublished study prepared by Collins Agricultural Consultants Inc., and Harris Environ

- mental Technologies, Inc. 397 p. Cahill, W.; Bade, T . (1988) Dissipation of Cyproconazole in Soil after Six Applications of Turf: Project No. 433018. Unpublished study prepared by Sandoz Crop Protection Corp. 121 p. Bade, T.; Guirguis, M. (1988) Dissipation of Cyproconazole in Soil after Six Applications to Turf: Addendum to Report No. 1: Lab Project No. 433018. Unpublished study prepared by Sandoz Crop Protection Corp. 130 p. Ali, S. (1990) Dissipation and Mobility of Cyproconazole in Soil: Lab Project Number: 433018

- 8. Unpublished study prepared by Sa doz Crop Protection Lab., in cooperation with Jensen Agricul

- tural Consultants, Inc. 253 p.
41800702 Ali, S. (1991) Interim Report on Dissipation and Mobility of Cypro

- conazole in Soil after Four Applications to Bare Ground in North Carolina: Lab Project Number: 433018: 10. Unpublished study prepared by Agricultural Systems, Assoc., and Harris Environ

- mental Technologies Inc. 323 p.
42430701 Ali, S. (1992) Final Report on Dissipation and Mobility of Cyproconazole in Soil after Four Applications
to Bare G round in Oregon: Lab Project Number: 433018: 17. Unpublished study prepared by Collins Agricultural Consultants, Inc. and Harris Environmental Technologies, Inc. 480 p.
42430702 Ali, S. (1992) Final Report on Dissipation and Mobility of Cyproconazole in S oil after Four Applications to Bare Ground in North Carolina: Lab Project Nos.: 433018; 16; 300785. Unpublished study prepared by Agricultural Systems Associates and Harris Environmental Technologies, Inc. 403 p.
40624302 Forbis, A. (1986) Uptake, Depurat ion and Bioconcentration of ?carbon 14|

- SAN 619F to Bluegill Sunfish (Lepomis macrochirus) (in Conjunction with Metabolism of SAN 619 F in Bluegill Sun

- fish: Project No. 35080. Unpublished study prepared by Analyti

- cal Bio

- chemistry Laboratories, Inc. 25 9 p.
40624303 Yu, C. (1988) Metabolism of SAN 619F in Bluegill Sunfish (Lepomis macrochirus) (in Conjunction with Uptake, Depuration and Bio

- accumulation of ?carbon 14|

- SAN 619F to Bluegill Sunfish): Pro

- ject No. 433015. Unpublished study prepared by Sa ndoz Crop Pro

- tection Corp. 16 p.
41220801 Addendum to 40624303 and 302

.



## 10.2. Submitted Ecological Toxicity Studies

MRID Citation

40606911 Donat, H. (1986) Acute Contact & Oral Toxicities of SAN 619F 40 WP 08 to Worker Honeybees: Report
No. 66'585/86. Unpublished stu

- dy prepared by Sandoz, Ltd. 13 p.

40607712 Carpy, S. (1984) Acute Oral LD50 Study in the Male and Female Rat with SAN 619 F: Project ID: 265/84. Unpublished study prepared by Sandoz Ltd. 16 p.

40607715 Ullmann, L. (1985) 4

- Hour Acute Dust Aerosol Inhalation Toxicity (LC50) SAN 619 F in Rats: Project No. 052975. Unpublished study prepared by RCC. 58 p.

40607723 Eschbach, B.; Aerni, R.; Karapally, J.; et al. (1987) SAN 619F: 2

- Generation Reproduction Study in Rats: Project No. 380

- R; Re

- port No. 6712/87. Unpublished study prepared by Sandoz, Ltd. 592 p.

40607730 Beavers, J. (1985) SAN 619 F: An Acute Oral Toxicity Study with the Bobwhite Quail: Project No. 102

- 119. Unpublished study prepared by Wildlife International. 32 p.

40607731 Beavers, J. (1985) SAN 619 F: A Dietary LC50 Study with the Bobwhite: Project No. 102

- 117. Unpublished study prepared by Wildlife International. 26 p.

40607732 Beavers, J. (1985) SAN 619 F: A Dietary LC50 Study with Mallard: Project No. 102

- 118. Unpublished study prepared by Wildlife International. 26 p.

### 34 40607733 Bowman, J. (1988) Acute Toxicity of SAN 619F Technical to Rainbow Trout (Salmo gairdneri): Final

Re port No. 36546. Unpublished study prepared by Analytical Bio

- Chemistry Laboratories, Inc. 181 p.

40607734 Bowman, J. (1988) Acute Toxicity of SAN 619F Technical Bluegill Sunfish (Lepomis macrochirus): Project No. 36545. Unpublished study prepared by Anal ytical Bio

- Chemistry Laboratories, Inc. 218 p.

40607735 Frazier, S. (1988) Acute Toxicity of SAN 619F to Daphnia magna: Report No. 36547. Unpublished study prepared by Analytical Bio

- Chemistry Laboratories, Inc. 178 p.

40607736 Donat, H. (1985) Labora tory Studies on the Acute Contact and Oral Toxicities of SAN 619F to Worker Honeybees: Report No. 66'562a. Unpublished study prepared by Sandoz Agrobiological Research. 7 p.

41061701 Hamburger, F. (1985) SAN 619F Fish Toxicity in the Rainbow Trout: Repor t No. 6395/85. Unpublished study prepared by Sandoz Ltd. 22 p.

41061702 Nicholson, R. (1986) Acute Toxicity of SAN 619F to Bluegill (Lepomis machrochirus): Study No.
10828

- 0785

- 6103

- 100; Report No. BW

- 85

- 11

- 1885. Unpublished study prepared by Springborn Bionomics, Inc. 20 p.

41125601 Donat, H. (1989) Laboratory Studies on the Acute Contact and Oral Toxicities of SAN 619F to Worker Honeybees: Report No. 66'562. Unpublished study prepared by Sandoz, Ltd. 11 p.

41125602 Donat, H. (1989) Laboratory Studies on the Acute Contact and Oral Toxicities of SAN 619F 40WP 08 to Worker Honeybees: Report No. 66'585. Unpublished study prepared by Sandoz Ltd. 15 p.

41259301 Jenkins, C. (1989) SAN 619: 21

- Day Rainbow Trout Toxicity St udy under Flow

- Through Exposure Conditions: Project ID 89/0197. Un

- published study prepared by Life Science Research Ltd. 34 p.

42656401 Hoberg, J. (1992) Cyproconazole Technical

-- Toxicity to the Freshwater Green Alga, Selenastrum capricornutum: Final R eport: Lab Project Number: 92

- 10

- 4475: 10828.0492.6116.430: 445/92/01. Unpublished study prepared by Springborn Labs., Inc. 63 p.

43187701 Drottar, K.; Swigert, J. (1993) Cyproconazole (SAN 619F): A Flow

- Through Life

- Cycle Toxicity Test with the Cladoceran (Daphnia magna): Final Report: Lab Project Number: DP301363: 131A/152. Unpublished study prepared by Wildlife International Ltd. 48 p.

4 3187702 Drottar, K.; Swigert, J.; Sved, D. (1993) Cyproconazole (SAN 619F): A 96

- Hour Shell Deposition Test with the Eastern Oyster (Crassostrea virginica): Final Report: Lab Project Number: DP/301330: 131A/ 149. Unpublished study prepared by Wildlife Inte rnational Ltd. 36 p.

43187703 Drottar, K.; Swigert, J. (1993) Cyproconazole (SAN 619F): A 96

- Hour Flow

- Through Acute Toxicity Test with the Saltwater Mysid (Mysidopsis bahia): Final Report: Lab Project Number: DP/ 301329: 131A/150. Unpublished study pre pared by Wildlife International Ltd. 35 p.

43187704 Drottar, K.; Swigert, J.; Sved, D. (1993) Cyproconazole (SAN 619F): A 96

- Hour Flow

- Through Acute Toxicity Test with the Sheepshead Minnow (Cyprinodon variegatus): Final Report: Lab Project Number:
DP301 331: 131A/151A. Unpublished study prepared by Wildlife International Ltd. 35 p.

43287701 Beavers, J.; Foster, J.; Marselas, G. et al. (1993) Cyproconazole: A Reproduction Study with the Mallard: Lab Project Number: 131/167. Unpublished study prepared by Wildlife International Ltd. 212 p.

43347001 Beavers, J.; Foster, J.; Marselas, G.; et al. (1993) Cyproconazole: A Reproduction Study with the Northern Bobwhite: Lab Project Number: 131

- 166. Unpublished study prepared by Wildlife International Ltd. 213 p.

46218511 Porch, J. (1997) Cyproconazole: A Toxicity Test to Determine the Effects of the Test Substance on Vegetative Vigor of Ten Species of Plants: Final Report. Project Number: 131/189, 437/96. Unpublished study prepared by Wildlife International, Ltd. 209 p.

46218512 Porch, J. (1997) Cyprocona zole: A Toxicity Test to Determine the Effects of the Test Substance on Seedling Emergence of Ten Species of Plants: Final Report. Project Number: 131/188, 436/96. Unpublished study prepared by Wildlife International, Ltd. 126 p.

46840822 Hamburger, F. (1 987) SAN 619 F: Acute Oral LD50 Study in CD

- 1 Male Mice: Final Report. Project Number: CBK/I/6828/87, T002154/06. Unpublished study prepared by Sandoz Ltd. Agrochemicals. 15 p.

46950008 Wheeler, J. (2006) Cyproconazole (SAN619): Early Life Stage Toxicity to Rainbow Trout (Oncorhyncus mykiss): Final Report. Project Number: T018649/04/REG, T018649/04. Unpublished study prepared by Syngenta Jealotts Hill International. 71 p.

### 35 47036201 Batscher, R. (2006) Effect on Survival, Growth and Reproduction of Daphnia magna in a Semi

- Static Test Over three Weeks: Cyproconazole: Final Report. Project Number: T022815/04, RCC/A99191. Unpublished study prepared by Research & Consulting Co., Ltd. 46 p.

47067101 Everett, C.; Wyeth, K.; Powley, W. (2007) Amended Final Report: Cyproconazole (SAN619)

- Growth Inhibition to Lemna gibba under Semi

- static Conditions. Project Number: T002449/06/REG, T002449/06. Unpublished study prepared by Syngenta Crop Protection Inc and Jealott's Hill Res. Station. 46 p.
47340801 Frey, L.; Marti n, K.; Beavers, J.; et al. (2007) Cyproconazole: A Reproductive Study with the Mallard: Final Report. Project Number: 528/238, T002365/03. Unpublished study prepared by Wildlife International, Ltd. 187 p.

### 36 

# Appendix A. SIP Modeling Results

Table 1. Inputs

Parameter Value

Chemical name Cyproconazole
Solubility (in water at 25 o C; mg/L) 140

Mammalian LD 50 (mg/kg

- bw) 270 Mammalian test species other Body weight (g) of "other" mammalian species 28

Mammalian NOAEL (mg/kg

- bw) 10.6 Mammalian test species laboratory rat Body weight (g) of "other" mammalian species

Avian LD 50 (mg/kg

- bw) 150 Avian test species northern bobwhite quail Body weight (g) of "other" avian species Mineau scaling factor 1.15

Mallard NOAEC (mg/kg

- diet) 7.3 Bobwhite quail NOAEC (mg/kg

- diet)

Table 2. Mammalian Results

Parameter Acute Chronic Upper bound exposure (mg/kg

- bw) 24.0800 24.0800 Adjusted toxicity value (mg/kg

- bw) 110.4468 8.1531 Ratio of exposure to toxicity 0.2180 2.9535

Conclusion* Exposure through drinking water alone is a

potential concern for
mammals Exposure through drinking water alone is a

potential concern for
mammals

Table 3. Avian Results

Parameter Acute Chronic Upper bound exposure (mg/kg

- bw) 113.4000 113.4000 Adjusted toxicity value (mg/kg

- bw) 108.0644 0.3622 Ratio of exposure to acute toxicity 1.0494 313.1111

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.

### 37 

# Appendix B

. STIR Modeling Results

Input

Application and Chemical Information

Enter Chemical Name Cyproconazole

Enter Chemical Use Fungicide 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) 291.8 Enter Chemical Vapor Pressure (mmHg) 2.60 E

- 07 Enter Application Rate (lb a.i./acre) 0.036

Toxicity Properties

**Bird**

Enter Lowest Bird Oral LD 50 (mg/kg bw) 150 Enter Mineau Scaling Factor 1.15 Enter Tested Bird Weight (kg) 0.178

**Mammal**

Enter Lowest Rat Oral LD 50 (mg/kg bw) 1020

Enter Lowest Rat Inhalation LC 50 (mg/L) 5.6 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 ) 4.08E

- 03

Maximum 1

- hour Vapor Inhalation Dose (mg/kg) 5.13E

- 04

Adjusted Inhalation LD 50 4.59E+00

Ratio of Vapor Dose to Adjusted Inhalation LD 50 1.12E

- 04 Exposure not Likely Significant

Maximum Post

- treatment Spray Inhalation Dose (mg/kg) 3.46E

- 03 Ratio of Droplet Inhalation Dose to Adjusted Inhalation
LD 50 7.53E

- 04 Exposure not Likely Significant



### Results Mammalian (0.015 kg )

Maximum Vapor Concentration in Air at Saturation (mg/m 3 ) 4.08E

- 03

Maximum 1

- hour Vapor Inhalation Dose (mg/kg) 6.45E

- 04

Adjusted Inhalation LD 50 3.33E+02

Ratio of Vapor Dose to Adjusted Inhalation LD 50 1.94E

- 06 Exposure not Likely Significant

Maximum Post

- treatment Spray Inhalation Dose (mg/kg) 4.35E

- 03 Ratio of Droplet Inhalation Dose to Adjusted Inhalation
LD 50 1.30E

- 05 Exposure not Likely Significant

### 38 

# Appendix C

. Half

- life Calculations

128993_DER-Fate_Cal culation_08-20-15.xlsx

Soil Photolysis (835.2410)

Aerobic Soil Metabolism (835.4100)

### 39

### 40

### 41