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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: Brian 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)
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Table of Contents

1. Executive Summary................................................................................................................ 3

2. Introduction............................................................................................................................. 4

2.1. Mode of Action ................................................................................................................ 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 Characterization........................................................................................................ 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 .............................................................................................. 38
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1. Executive Summary

The Environmental Fate and Effects Division (EFED) has completed the preliminary problem 

formulation for the ecological 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

antimicrobial product of cyproconazole as a wood preservative for structural lumber (USEPA, 

2015b). 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 risk assessments in support of registration review and provides

an overview of the environmental fate, ecological effects, potential risks associated with the use,

and uncertainties 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 cyproconazole were conducted in 2005, 2007, 2011, and 

2012 (USEPA 2005, 2007b, 2011, 2012). For registered outdoor uses, an acute and chronic risk

concern was identified for small birds eating short grass only. Additional risk concerns were 

identified for proposed 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 toxicity
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 Non-guideline (Tier 2): Semi-field testing for pollinators (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

Cyproconazole ((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, soybean, field and seed corn, and peanuts. Cyproconazole comprises 

two diastereomers: 2RS,3RS;-2-(4-chlorophenyl)-3-cyclopropyl-1-(1H-1,2,4-triazol-1-yl)butan2-ol and (2RS,3SR)-2-(4-chlorophenyl)-3-cyclopropyl-1-(1H-1,2,4-triazol-1-yl)butan-2-ol. 

There are five active Section 3 registrations for 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 formulation (EPA Reg. No. 352-883). Cyproconazole is the sole active 

ingredient in one of the formulated products and it is co-formulated with strobilurin fungicides in 

the other three products.

EFED evaluated the most recent ecological risk assessments for cyproconazole 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-demethylase), 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 cell 
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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

through 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% azoxystrobin), and DupontTM Aproach® Prima Fungicide (EPA 

Reg. No. 352-883; 7.17% cyproconazole, 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 single 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 crop treated, 10,000 lbs a.i./yr) and wheat (<2.5% of crop treated, 20,000 lbs a.i./yr) (USEPA, 

2015a). 

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 given use for the risk 

assessment. For labels that do not include a maximum annual application 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 Cyproconazole

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 & 

Triticale2 0.036 0.036 NS NS1 NS 14 Aerial spray, 

Ground 

spray, 

Chemigation

Corn2 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

NS=Not Specified; App.=Applications; CC=Crop Cycle 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 than 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 composite 
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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, 2015b). 

4. Conclusions from 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, 2007b), 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 LOC 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 withdrawal/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 Currently Registered Uses of Cyproconazole
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Table 2. Evidence of Risk to Taxonomic Groups from Currently Registered 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: Cyproconazole is practically 

non-toxic to adult honey 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 2007, based on registration of new 

uses for spray application to cereals (wheat and triticale), corn, and soybeans (USEPA, 2007).

Tier I FIRST modeling indicates 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-in10-year annual mean). For groundwater, screening level exposure estimates using the Tier I SCIGROW model indicate 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-triazole 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 aquatic 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 create 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_ders/aquatic_life_benchmark.htm
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5. Environmental Fate and Transport

5.1. Chemical Identity 

Cyproconazole is a mixture of four stereo-isomers, two diastereomeric pairs of enantiomers:

2RS, 3RS;-2-(4-chlorophenyl)-3-cyclopropyl-1-(1H-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. Fate 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 and 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 moderate 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 half-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/H2O/MeOH) within the 37 day study period,

suggesting that the mechanism may be due to strong adsorption of cyproconazole to soil 

overtime instead of photolysis (MRID 40607707).

Cyproconazole slowly degrades in aerobic soil (t1/2=1160 days, 90th percentile upper 

confidence bound from 3 soils) and aquatic environments (t1/2= 990 days - stable). In aerobic 

soil studies, half-lives of cyproconazole range from 204 to 1360 days. The only 

transformation product identified aside from CO2 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 CO2 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 (t1/2= >365). The soil bound fraction of 

cyproconazole increased over time with direct correlation to study duration. The soil bound 

fraction maximum was reported at 36.3% for North Carolina soil at 210 days (MRID 
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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 half-life in 

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

2,310.5 days, although no major transformation products were observed and the only minor 

transformation product was CO2 (MRID 46840810). In 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∙m3∙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 192 days in a Maryland 

turf study, 252 days in an Oregon bare ground study, and 160 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 halflife of cyproconazole on the outer surface of soybean leaves was 2.5 days. Residues 

incorporated into the soybean leaves (defined as non-washable fraction) had a half-life of 9.5 

days. The wash-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 summarizes the chemical and environmental fate properties of cyproconazole.
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Table 3. Chemical Properties and Environmental Fate Parameters of Cyproconazole

Parameter Value Source

Selected Physical/Chemical Parameters

Molecular mass (molecular formula) 291.8 (C15H18ClN3O)

MRID 46840803

Vapor pressure (25°C) 2.6 x 10-7 torr (mm Hg)

Aqueous solubility 108 mg/L (22°C)

140 mg/L (25°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

Octanol-to-water partition coefficient (log 

KOW) 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-life1 89.2 days2

Aerobic soil metabolism half-life (20-25°C)

203.9 days

227.4 days2,3

1360 days2

>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 Kf 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.74-79
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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). CO2 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.
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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-(1H1,2,4-triazol-1-yl)butan-2-ol

CAS Name: α-(4-

chlorophenyl)-α-(1-

cyclopropylethyl)-1H-1,2,4-

triazole-1-ethanol

CAS No.: 94361-06-5

Formula: C15H18ClN3O

MW: 291.8 g/mol

SMILES:

CC(C1CC1)C(CN2C=NC=N2)(C3

=CC=C(C=C3)Cl)O

TRANSFORMATION PRODUCTS

Triazolyl 

Alanine /

(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 Dioxide IUPAC: Carbon dioxide

Formula: CO2

MW: 44 g/mol

SMILES: C(=O)=O

O C O

Aerobic soil 46840806 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)

46840806 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 

[14C] 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 presented 

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 (LC50s 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), the 59-day post-hatch toxicity of cyproconazole to rainbow trout 

was studied under flow-through conditions at concentrations up to 0.305 mg a.i./L. The NOAEC 

for wet weight was 0.161 mg 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 EC50 of

0.026 mg a.i./L and a NOAEC of 0.0059 mg a.i./L (MRID 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 

fish1

Acute

TGAI

(96.2%)

Rainbow Trout

(Oncorhynchus 

mykiss)

96-hr LC50 = 19

(Slightly toxic)

40607733

Acceptable

TGAI

(96.2%)

Bluegill Sunfish 

(Lepomis 

macrochirus)

96-hr LC50 = 21

(Slightly toxic)

40607734

Acceptable

21-day TGAI

(96.2%) Rainbow Trout

21-d LC50 = 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-life 

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 

variegatus)

96-hr LC50 = 21

(Slightly toxic)

43187704

Acceptable

Chronic NA Sheepshead Minnow NOAEC = 0.178

Based on ACR2 NA

Aquatic Invertebrates

Freshwater 

invertebrates

Acute TGAI

(96.2%)

Water Flea

(Daphnia magna)

48-hr EC50 = 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 EC50 = 2.6

(Moderately toxic)

43187702

Acceptable

Acute TGAI

(95.6%)

Mysid Shrimp 

(Mysidopsis bahia)

96-hr LC50 = 9.6

(Moderately toxic)

43187703

Acceptable

Chronic NA Mysid Shrimp NOAEC = 0.007

Based on ACR3 NA

Aquatic Plants

Aquatic 

plants and 

algae

Vascular TGAI

(98.2%)

Duckweed

(Lemna gibba)

EC50 = 0.094

7-d NOAEC/LOAEC = 

0.0245 / 0.0457

(Frond number)

47067101

Acceptable

NonvascularTGAI

(95.8%)

Green Algae 

(Pseudokirchneriella 

subcapitata)

EC50 = 0.026

5-d NOAEC/LOAEC = 

0.0059 / 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 LC50 / Rainbow trout NOAEC = 19 mg/L / 0.161 mg/L = 118

Estimated sheepshead minnow NOAEC = Sheepshead minnow 96-hour LC50 / ACR = 21 mg/L / 118 = 0.178 

mg/L 3 ACR = Daphnia magna 48-hour LC50 / Daphnia magna NOAEC = 26 mg/L / 0.019 mg/L = 1368

Estimated mysid shrimp NOAEC = mysid shrimp 96-hour LC50 / ACR = 9.6 mg/L / 1368 = 0.007 mg/L

6.2. Effects to Terrestrial Organisms

Available acute oral and dietary toxicity data suggest that cyproconazole 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 (MRIDs 43287701, 47340801) showed effects 

on multiple reproductive endpoints including live embryos/viable embryos, normal 

hatchlings/eggs set, normal hatchlings/live embryos, and hatching 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 eggs laid, eggs set, viable embryos, live 

21-day normal embryos, normal hatchlings, 14-day survivors and several growth effects 

occurred at 250 mg a.i./kg-diet (NOAEC = 50 mg a.i./kg-diet). A two-generation rat 

reproduction study (MRID 40607723) 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 (Phaseolus vulgaris), carrot 

(Daucus carota), lettuce (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 tomato

(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 weight were the most 

sensitive endpoints in both studies. Cabbage was the most sensitive species tested, with an IC25

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 Category or 

Most Sensitive Endpoints)

MRID and 

Study 

Classification

Birds1

Acute Oral TGAI

(95.6%)

Bobwhite quail

(Colinus 

virginianus)

LD50 = 150 mg/kg-bw

(Moderately toxic)

40607730

Acceptable

Sub-acute 

Dietary

TGAI

(95.6%) Bobwhite quail LC50 = 816 mg/kg-diet

(Moderately toxic)

40607731

Acceptable

TGAI

(95.6%)

Mallard duck (Anas 

platyrhynchus)

LC50 = 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 Category 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

Mammals2

Acute Oral

TGAI Laboratory rat

(Rattus norvegicus)

LD50 = 1020 mg/kg-bw

(Slightly toxic)

40607712

Acceptable

TGAI Mouse 

(Mus musculus)

LD50 = 270 mg/kg-bw

(Moderately toxic)

46840822

Acceptable

Acute 

Inhalation TGAI Laboratory rat 4-hr LC50 >5.6 mg/L 40607715Acceptable

Chronic (2-

generation 

Reproduction)

TGAI

(95.6%) Laboratory rat

NOAEC = 120 mg/kg-diet

NOAEL = 8.29 mg/kg bw/day

(No effects)

40607723

Acceptable

Terrestrial 

Invertebrates

Acute Contact

TGAI

(95.6%)

Honey bee

(Apis mellifera)

LD50 >100 μg/bee

(Practically non-toxic)

41125601

Acceptable

TEP

(40%) Honey bee LD50 >100 μg/bee(Practically non-toxic)

41125602

Acceptable

Acute Oral

TGAI

(95.6%) Honey bee LD50 >1000 μg/bee

(Practically non-toxic)

41125601

Acceptable

TEP

(40%) Honey bee LD50 >50 μg/bee(Practically non-toxic)

41125602

Acceptable

Terrestrial 

Plants

Seedling 

Emergence

TEP

(30.6%)

Monocot: Onion

IC25 >0.58 lbs/A

NOAEC = 0.58 lbs/A

(Dry weight) 46218512

Acceptable

Dicot: Cabbage

IC25 = 0.091 lbs/A

NOAEC = 0.066 lbs/A

(Fresh weight)

Vegetative 

Vigor

TEP

(30.6%)

Monocot: Ryegrass

IC25 >0.58 lbs/A

NOAEC = 0.58 lbs/A

(Dry weight) 46218511 

Acceptable

Dicot: Cabbage

IC25 = 0.50 lbs/A

NOAEC = 0.090 lbs/A

(Dry 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 have been reported to the Agency. When available, EIIS includes date and location 

of an incident, type and magnitude of effects observed in various species, use(s) of pesticides 

known or suspected of contributing to the incident, and results of any chemical residue analysis 

or other analyses conducted during incident investigation. EIIS incidents are categorized 

according to the certainty that the incident resulted from pesticide exposure. The Avian 

Monitoring System (AIMS) is a database administered by the American Bird Conservancy that 

contains publicly available data on reported avian incidents involving pesticides. Many of the 

incidents listed in this database are also in the EIIS. Additionally, the U.S. EPA Office of 

Pesticide Programs Incident Data System (IDS) compiles aggregate incidents 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 of July 22, 2015, no incidents were 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 aquatic and 

terrestrial organisms. Drinking water and inhalation exposure pathways were screened using the 

SIP (Screening Imbibition Program) 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 that vapor 

and droplet inhalation are not likely to be exposure pathways of concern for birds or mammals 

(see Appendix B). SIP and STIR are described in detail 

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

8. Analysis Plan

8.1. Stressors of Concern

Ecological Risk 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 Exposure 

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. The Surface Water Concentration 

Calculator (SWCC) is currently the model typically used to estimate aquatic exposure. T-REX

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

On the USGS NAWQA surface and groundwater database 

(http://cida.usgs.gov/nawqa_queries_public/), cyproconazole was 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). Cyproconazole 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 monitored 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, cyproconazole 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/docs/emon/surfwtr/surfcont.htm).

8.3. Measures of Effect 

The most sensitive of the toxicity data presented in Section 6 of this problem formulation will be 

used to calculate risk quotients. Any additional information submitted by the registrant or found 

in the open literature prior to conduct of the risk assessment will also be considered. The open 

literature studies are identified using EPA’s ECOTOXicology database (ECOTOX) (USEPA, 

2007a), which employs a literature search engine for locating chemical toxicity data for aquatic 

life, terrestrial plants, and wildlife. The evaluation of both sources of data can also provide 

insight into the direct and indirect effects of pesticides on biotic communities from loss of 

species that are sensitive to the 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 Academy 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 

obligations under the ESA and FIFRA. EPA will address concerns specific to cyproconazole in 

connection with the development of its final registration 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 between the EPA and the Services. Details of the joint Interim Approaches are 

contained in the November 1, 2013 white paper, Interim Approaches for National-Level 

Pesticide Endangered Species Act Assessments Based on the 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 listed 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 designated critical habitat, to be conducted 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 completed for this particular registration review case. This assessment will 

allow EPA to focus its future evaluations on the types of species where the potential for effects 

exists, once the scientific methods being developed by the agencies have been fully vetted. Once 

the agencies 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 as 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 order 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 Cyproconazole

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

40624303 Acceptable No None

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 identify 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 (MRIDs

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 nonvascular 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 nonvascular 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

43287701 Acceptable No None

47340801 Supplemental

Nonguideline 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.

Nonguideline

(Tier I)

Honey bee adult 

acute oral toxicity

41125601 Acceptable

No None

41125602 Acceptable

Nonguideline

(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.

Nonguideline

(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.

Nonguideline

(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

Nonguideline

(Tier II)

Semi-field testing 

for pollinators 

(tunnel or colony 

feeding studies)

None NA Yes

See justification tables 

below for additional 

details.

Nonguideline

(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 46218511 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 exposed. 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. 

Because of the potential for pollen and nectar to be contaminated with pesticide residues, and 

subsequently brought back to the hive, it is important to determine the acute oral toxicity of this 

compound to 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-assessmentguidance. 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-larvaltoxicity-test-single-exposure_9789264203723-en.

Practical Utility of the Data

How will the data be used?

The Tier I acute oral toxicity data 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 insects, 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 understanding 

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 will be assumed.

How could the data impact the Agency’s future decision-making?

The data will inform the determination required under FIFRA or the ESA as to whether continued 

registration of a pesticide is likely to result in unreasonable adverse effects to non-target species or is 

likely to adversely affect listed threatened or endangered species and/or modify their designated critical 
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 sublethal effects of chronic oral exposure on adult terrestrial invertebrates and will assist in 

determining whether the sensitivity of adult bees differs from that of earlier life stages. Because of the 

potential for pollen and nectar to be contaminated with pesticide residues, and subsequently brought 

back to the hive, it is important to determine the chronic oral toxicity of this compound to adult 

honeybees and other pollinators.

The Office of Pesticide Programs has made available a guidance regarding ecological 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 risks from specific routes of exposure. The guidance can be found at: 

http://www2.epa.gov/pollinator-protection/pollinator-risk-assessment-guidance. Study design elements 

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-oraltoxicity-test_9789264070165-en.

Practical Utility of the Data

How will the data be used?

The Tier I chronic oral toxicity data 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 pollinators 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 assumed.

How could the data impact the Agency’s future decision-making?

The data will inform the determination required under FIFRA or the ESA as to whether continued 

registration of a pesticide is likely to result in unreasonable adverse effects to non-target species or is 

likely to adversely affect listed threatened or endangered species and/or 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 exposed. 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 

pollen and nectar to be contaminated with pesticide residues, and subsequently brought back to the 

hive, it is important to determine chronic larval/pupal toxicity and whether adult emergence is 

adversely affected. This study will provide information on whether 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 draft 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 data 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 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 pollinators. These data 

will also assist in determining whether early life stages of the bee differ in their sensitivity to pesticides 

relative to adults. 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 endangered species and/or modify their designated critical 

habitat. Without these data, EPA may need to presume risk which will limit the flexibility of pesticide 

products to comply with FIFRA and the ESA, and could result in use restrictions. 

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 the 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 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 under relatively controlled exposure conditions of a semi-field study. 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 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 

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 test of whole colonies is a relatively controlled 

study, i.e., bees are confined to a specific area, that is designed to represent potential field-level 

exposure and account for hive dynamics, which are not achievable from other pollinator studies. This 

study will be used to determine whether adverse effects to 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 invertebrates. 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 species or their designated critical 

habitat. Without these data, EPA may need to presume risk which will limit the flexibility of pesticide 

products to comply with FIFRA and the ESA, and could result in significant use restrictions.

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 terrestrial 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 from 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 naturally 

beyond the spiked food. Results from the feeding study will help to refine the screening-level risk 

assessment for beneficial terrestrial invertebrates that were based on Tier 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 which 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 

quantification 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). Residues 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 guidance regarding ecological testing for 

invertebrates with the honeybee. The guidance can be found at: http://www2.epa.gov/pollinatorprotection/pollinator-risk-assessment-guidance.

Practical Utility of the Data
30

How will the data be used?

Measured residue data 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 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 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. 2000. 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 Environmental Fate and Effects 

Division. DP Barcode 320682, dated February 28, 2006.

USEPA. 2006 b. 1,2,4-Triazole, Triazole Alanine, Triazole Acetic Acid: Human Health 

Aggregate Risk Assessment in Support of Reregistration and Registration Actions for 

Triazole-derivative Fungicide Compounds. Office of Pesticide Programs Health Effects 

Division and Environmental Fate and Effects Division. DP Barcode 322215, dated 

February 7, 2006.
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 Barcode 343771, dated 9/11/07.

USEPA. 2007a. 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, Environmental 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 (Cereal 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 Registration 

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 Programs, 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 Use on Turf. U.S. Environmental Protection 

Agency, Office of Pesticide Programs, Environmental Fate and Effects Division. 

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

USEPA. 2015a. Cyproconazole Screening Level Usage Analysis (SLUA). U.S. Environmental 

Protection Agency, Office of Pesticide Programs, Biological and Economic Analysis 

Division. Dated 4/10/15.

USEPA. 2015b. Risk Assessment of New use of Cyproconazole for the Protection of Engineered 

and Composite Wood Products. DP 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 Amendment. 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. Unpublished 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. Agrochemicals. 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. (1985) 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: 

3760-24-11-85. 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 Mobility 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 Ground 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 Soil 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, Depuration 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. 259 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 Sandoz 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 

Report 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 Analytical 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) Laboratory 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: Report 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 Study 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 Report: 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. 

43187702 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 International 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 prepared 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: 

DP301331: 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) Cyproconazole: 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. (1987) 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.

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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 25oC; mg/L) 140

Mammalian LD50 (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 LD50 (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) 2.60E-07

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

Toxicity Properties

Bird

Enter Lowest Bird Oral LD50 (mg/kg bw) 150

Enter Mineau Scaling Factor 1.15

Enter Tested Bird Weight (kg) 0.178

Mammal

Enter Lowest Rat Oral LD50 (mg/kg bw) 1020

Enter Lowest Rat Inhalation LC50 (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/m3) 4.08E-03

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 5.13E-04

Adjusted Inhalation LD50 4.59E+00

Ratio of Vapor Dose to Adjusted Inhalation LD50 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 

LD50 7.53E-04 Exposure not Likely Significant

Results Mammalian (0.015 kg )

Maximum Vapor Concentration in Air at Saturation 

(mg/m3) 4.08E-03

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 6.45E-04

Adjusted Inhalation LD50 3.33E+02

Ratio of Vapor Dose to Adjusted Inhalation LD50 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 

LD50 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
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