UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON D.C., 20460 

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION 

December 10, 2015 

PC Code: 125619 

DP Barcode: 428303 

MEMORANDUM 

SUBJECT: 

FROM: 

TO: 

Metconazole: Preliminary Problem Formulation for Environmental Fate, 

Ecological Risk, Endangered Species, and Drinking Water Exposure Assessments 

in Support of Registration Review 

Michael Lowit, Ph.D., Ecologistt:J#. '&-~ t>-/1Pj,S-- ,_c, -t\~) He Zhong, Ph.D., Biologist -J:r/~ :::= \·.::i-lio\ 1S- C J ~( Sujatha Sankula, Ph.D., Branch Chie ;~::J..- ~~ .~1.dyi......---

Environmental 

Environmental Fate 

Risk 

and 

Branch 

Effects 

I 

Division (7507P) 

~ 

Jordan Page, Chemical Review Manager 

Jill Bloom, Team Leader 

Linda Arrington, Branch Chief 

Risk Management and Implementation Branch V 

Pesticide Re-evaluation Division (7508P) 

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

formulation for the environmental fate , ecological risk, endangered species, and drinking water 

exposure assessments to be conducted as part of the Registration Review of the fungicide 

metconazole (CAS# 125116-23-6). Functioning as the first stage of the risk assessment process 

for registration review, this problem formulation provides an overview of what is currently 

known about the environmental fate and ecological effects associated with metconazole and its 

degradates. It also describes the preliminary ecological risk hypothesis and analysis plan for 

evaluating and characterizing risk to non-target species in support of the registration review of 

metconazole. This document also recommends studies that should be included in a generic data 

call-in (DCI) to address uncertainties surrounding the environmental fate and potential ecological 

effects of metconazole. 
2

EFED recommends the following studies to reduce uncertainty in the risk assessment:

• 850.2100: Avian oral toxicity (passerine species) (metconazole; TGAI)

• Non-guideline: Chronic toxicity to benthic invertebrates (whole sediment; 3 test species: 

freshwater amphipod, freshwater midge, and estuarine/marine amphipod) –

(metconazole; TGAI)

o EFED recommends that the registrant consider Agency-wide guidelines for 

chronic testing of freshwater and estuarine/marine organisms1,2 because the 850 

guidelines are in the process of being finalized. A protocol must be submitted for 

review prior to initiating the studies.

o The study design of the chronic studies could be modified to address the 

unexplained effects on growth observed in the available subchronic tests in lieu of 

additional subchronic testing on the freshwater midge and amphipod. 

• Non-guideline (Tier I): Honeybee adult chronic oral exposure (metconazole; TGAI)

• Non-guideline (Tier I): Honeybee larval acute oral exposure (metconazole; TGAI)

• Non-guideline (Tier I): Honeybee larval chronic oral exposure (metconazole; TGAI)

• Non-guideline (Tier II): Residue in pollen and nectar (recommendation pending risk 

identified in Tier I studies) (TEP)

• Non-guideline (Tier II): Semi-field testing for pollinators (tunnel and feeding studies) 

(recommendation pending risk identified in Tier I studies) (TEP)

• 850.3040 (Tier III): Full-field testing for pollinators (recommendation pending risk 

identified in Tier II studies) (TEP)

• 850.6100: Environmental chemistry method and independent laboratory validation 

(ECM/ILV) reports for analytical method in water (metconazole; TGAI; LOQ <3 μg/L)

Toxicity data from other sources (e.g., other conazoles) may be used in the absence of data for 

metconazole. Use of surrogate data may over or underestimate risk of metconazole use.

EFED recommends the following label changes to reduce uncertainty in the risk assessment:

EFED requests that the registrant provide maximum annual application rates per acre (maximum 

lb ai/A/year) on all labels in addition to the currently labeled per-crop or per-season rates on 

some labels. Potential accumulation of metconazole is a concern given that it is persistent and 

because many crops may have multiple crop seasons per year. In the absence of labeled 

maximum annual application rates (or labeled maximum number of crop seasons/year), EFED 

will assume multiple crop seasons for applicable crops and make conservative assumptions about 

the maximum number of crop seasons per year based on the best available information. In 

addition, some single application rates are provided in terms of lb ai/volume. EFED requests 

that the registrant review all labels to ensure that rates are also presented in terms of lb ai/area.

 1 USEPA 2000. Methods for Measuring the Toxicity and Bioaccumulation of Sediment-associated Contaminants 

with Freshwater Invertebrates. EPA 600/R-99/064. http://www.epa.gov/nscep 2 USEPA 2001. Methods for Assessing the Chronic Toxicity of Marine and Estuarine Sediment-associated 

Contaminants with the Amphipod Leptocheirus plumulosus. EPA 600/R-01/020. http://www.epa.gov/nscep
3

Problem Formulation for the Environmental Fate, 

Ecological Risk, Endangered Species, and Drinking 

Water Exposure Assessments in Support of the 

Registration Review of Metconazole

CAS: 125116-23-6

PC Code: 125619

Environmental Fate and Effects Division

Prepared by:

Michael Lowit, Ph.D., Ecologist

He Zhong, Ph.D., Biologist

U.S. Environmental Protection Agency

Office of Pesticide Programs

Environmental Fate and Effects Division

Environmental Risk Branch I

1200 Pennsylvania Ave., NW

Mail Code 7507P

Washington, DC 20460

Reviewed by:

Sujatha Sankula, Branch Chief

Stephen Wente, Biologist

Gregory Orrick, Risk Assessment Process Leader

H3C

H3C

N

N N

HO

Cl
4

Table of Contents

1. Purpose........................................................................................................................................ 5

2. Problem Formulation .................................................................................................................. 5

2.1. Nature of Regulatory Action................................................................................................ 5

2.2. Previous Assessments.......................................................................................................... 5

2.2.1. Ecological Risk Assessments........................................................................................ 5

2.2.2. Drinking Water Exposure Assessments........................................................................ 6

3. Stressor Source and Distribution ................................................................................................ 6

3.1. Mechanism of Action.......................................................................................................... 6

3.2. Overview of Pesticide Use and Usage ................................................................................ 7

3.3. Environmental Fate and Transport.................................................................................... 10

3.4. Monitoring Data................................................................................................................ 14

3.5. Clean Water Act................................................................................................................ 14

4. Receptors.................................................................................................................................. 15

4.1. Effects to Aquatic Organisms........................................................................................... 15

4.2. Effects to Terrestrial Organisms....................................................................................... 18

4.3. Incident Databases Review............................................................................................... 21

5. Exposure Pathways of Concern ............................................................................................... 22

6. Analysis Plan ........................................................................................................................... 23

6.1. Stressors of Concern .......................................................................................................... 23

6.2. Measures of Exposure........................................................................................................ 24

6.3. Measures of Effect ............................................................................................................. 24

6.4. Integration of Exposure and Effects .................................................................................. 25

6.5. Endangered Species Assessments...................................................................................... 25

6.6. Endocrine Disruptor Screening.......................................................................................... 26

6.7. Drinking Water Assessment .............................................................................................. 26

6.8. Preliminary Identification of Data Gaps............................................................................ 26

6.8.1. Environmental Fate Data ............................................................................................ 26

6.8.2. Ecological Effects Data............................................................................................... 27

7. References................................................................................................................................ 32

APPENDIX A. Metconazole and its Environmental Degradates................................................. 34

APPENDIX B. ECOSAR Output ................................................................................................ 37

APPENDIX C. SIP v.1.0 Inputs and Outputs.............................................................................. 38

APPENDIX D. STIR v.1.0 Inputs and Outputs........................................................................... 39
5

1. Purpose

The purpose of this problem formulation is to provide an understanding of what is known about 

the environmental fate, ecological effects, and currently registered uses of metconazole. This 

document provides a plan for analyzing data relevant to metconazole and for conducting 

environmental fate, ecological risk, endangered species, and drinking water exposure 

assessments for its registered uses. Additionally, this problem formulation identifies data gaps, 

uncertainties, and potential assumptions used to address those uncertainties relative to 

characterizing the potential ecological risk associated with the registered uses of metconazole.

2. Problem Formulation

2.1. Nature of Regulatory Action

As part of the implementation of the Registration Review program3 pursuant to Section 3(g) of 

the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the Agency is beginning its 

evaluation of metconazole to determine whether it continues to meet the FIFRA standard for 

registration. This problem formulation in support of the registration review of metconazole will 

be posted in the initial docket which will be open to the public phase of the review process.

2.2. Previous Assessments

2.2.1. Ecological Risk Assessments

Metconazole was first registered in the United States in 2007 as a systemic fungicide. It is 

currently registered for use on a variety of food crops and turf. Previous Section 3 

assessments for metconazole typically identified risk concerns for birds (acute and chronic), 

mammals (acute and chronic), aquatic plants, fish (chronic), and aquatic invertebrates 

(chronic) (most recent: USEPA, 2014a).

4

 Less commonly, a risk concern was identified for 

marine/estuarine invertebrates (acute) and terrestrial plants (listed species).

In some cases the risk concern is from repeated use of metconazole. This is because 

exposure may not be high enough after a single year of use to be of concern; however, 

available environmental fate data suggest that metconazole residues may increase (i.e.,

accumulate) over time from repeated application. Figure 1 shows an example from a recent 

risk assessment of the relationship between exposure, repeated application, and risk to 

aquatic organisms (USEPA, 2011). For this corn use scenario there is a potential risk 

concern for several taxa; however, the timing of the concern varies: after a single year of use 

for some taxa (e.g., freshwater fish) and after repeated use over several years for other taxa

(e.g., freshwater invertebrates).

 3 http://www2.epa.gov/pesticide-reevaluation/registration-review-process 4 Earlier risk assessments relied on toxicity data from other conazoles due to a lack of valid studies. More recent 

risk assessments incorporate metconazole toxicity data; therefore, risk conclusions based on other conazoles are not 

reported here.
6

Figure 1. PRZM/EXAMS daily estimated environmental concentrations (EEC) for metconazole 

applied to corn (MS Corn Standard scenario for annual applications) with metconazole aquatic 

toxicity assessment endpoints (USEPA, 2011). The intersections of the blue line (daily EEC) 

and horizontal lines (toxicity values) represent the projected time when the risk quotient (RQ) is 

equal to the Agency’s levels of concern (LOC). The daily EECs represent repeated use from 

year-to-year starting in 1960 (i.e., year 1). Note that the estuarine/marine invertebrate NOAEC 

(11 μg ai/L) was an estimated value. A study was subsequently submitted showing a NOAEC ≥ 

59 μg ai/L.

2.2.2. Drinking Water Exposure Assessments

The most recent drinking water assessment (DWA) in support of human health risk assessment 

was conducted in 2014 to support the registration of metconazole on pea and bean (dried shelled, 

subgroup 6C) and sunflower (subgroup 20B) (USEPA, 2014b). The maximum estimated 

drinking water concentrations (EDWC) in surface water are 49.5 μg/L for the annual peak 

(acute) concentration, 43.9 μg/L for the annual mean concentration and 22.8 μg/L for the 30 year 

annual mean concentration (cancer, chronic) in surface water. The maximum PRZM-GW 

groundwater acute concentration is 51.8 μg/L and chronic concentration is 20.0 μg/L.

3. Stressor Source and Distribution

3.1. Mechanism of Action

Metconazole is a broad-spectrum triazole fungicide that works by inhibiting demethylation and 

YEAR

1965 1970 1975 1980 1985 1990

Daily EEC (

μg/L)

0

25

50

75

100

125

Vascular plant NOAEC 0.51 μg a.i./L Fresh Water fishNOAEC:2.9 μg a.i./L

Estuarine/Marine invertebrate NOAEC: 11 μg a.i./L

Vascular plant EC50: 22 μg a.i./L

Fresh water invertebrate NOAEC: 31 μg a.i./L
7

other processes in sterol biosynthesis. Metconazole is systemic, so it is quickly absorbed into 

plant tissue and can move up, but not down, in the plant. 

3.2. Overview of Pesticide Use and Usage 

Metconazole uses and application rates are summarized in Table 1. This information was 

obtained from the most recent Label Use Information System (LUIS) report provided by the 

Biological and Economic Analysis Division (BEAD) (USEPA, 2015a). The registration review 

risk assessment will be based on current label information at the time of assessment as provided 

by BEAD.

To reduce uncertainty in the risk assessment, EFED requests that the registrant provide 

maximum annual application rates per acre (maximum lb ai/A/year) on all labels in addition to 

the currently labeled per-crop or per-season rates on some labels. Potential accumulation of 

metconazole is a concern given that it is persistent and because many crops may have multiple 

crop seasons per year. In the absence of labeled maximum annual application rates (or labeled 

maximum numbers of crop seasons/year), EFED will assume multiple crop seasons for 

applicable crops and make conservative assumptions about the number of crop seasons per year 

based on the best available information. 

Some single application rates are provided in terms of lb ai/volume. EFED requests that the 

registrant review all labels to ensure that rates are also presented in terms of lb ai/area.

There are also some discrepancies identified in the LUIS report such as the single and annual 

maximum application rates differing when a single application is permitted per year.

Some labeled uses do not state the minimum re-application intervals (see Table 1 for a partial 

list5

). Although EFED will make assumptions in the absence of application interval restrictions, 

the uncertainty will likely have a minimal impact on exposure estimates given that metconazole 

is persistent.

Table 1. Maximum Registered Use Patterns for Metconazole

Use Method of 

Application

Maximum

Single

Application 

Rate (lb ai/A)1

Maximum 

Number of 

Applications

Minimum 

Application 

Interval (days)

Season/Crop or 

[Annual]

Maximum

Application Rate

(lb ai/A)

Bushberry 

(subgroup 13-

07B)

Ground and 

aerial spray; 

chemigation

0.0781 3 7 0.2344

Tuberous and 

corm vegetables 

(subgroup 1C)

Ground and 

aerial spray; 

chemigation

0.125 4 7 0.5

 5 Table 1 lists maximum application rates only. Some labels or lower application rates may also lack information 

about the maximum number of applications per year and minimum re-application intervals.
8

Use Method of 

Application

Maximum

Single

Application 

Rate (lb ai/A)1

Maximum 

Number of 

Applications

Minimum 

Application 

Interval (days)

Season/Crop or 

[Annual]

Maximum

Application Rate

(lb ai/A)

Barley

Ground and 

aerial 

broadcast; 

chemigation; 

directed spray; 

banded 

0.0997 2 6 0.1994

Seed treatment 0.000022682 NS NS NS

Canola\Rape Seed treatment 0.000014322 NS NS NS

Canola 

(unspecified)

Ground and 

aerial spray;

chemigation 

0.125 1 NA 0.125

Seed treatment 0.00002632 NS NS NS

Corn

Ground and 

aerial 

broadcast;

chemigation;

direct spray; 

banded

0.0821 4 or NS 7 0.3519

Seed treatment 0.000152 NS NS NS

Cotton

Ground and 

aerial 

broadcast;

chemigation; 

direct spray; 

banded

0.0821 3 7 0.2463

Seed treatment 0.0001052 NS NS NS

Golf course turf Spot treatment 0.00633 2 14 [2]

Ground spray 0.6 2 14 [2]

Oats

Ground and 

aerial 

broadcast;

chemigation; 

direct spray; 

banded

0.0997 2 6 0.1994

Seed treatment 0.000022682 NS NS NS

Ornamental 

(sod farm) Spot treatment 0.00633 2 14 [2]

Ornamental 

(lawns, turf, sod 

farm)

Ground spray 0.6 2 14 [2]

Ornamental 

(unspecified)

Foliar 

treatment 0.0748 1 14 [0.1703]4

Ground spray 0.1255 NS 14 [2]

Ground spray 0.272 NS 14 [2]

Drench 0.0003124576 NS 14 [2]

Peanuts

Ground and 

aerial spray;

chemigation

0.125 4 14 0.5
9

Use Method of 

Application

Maximum

Single

Application 

Rate (lb ai/A)1

Maximum 

Number of 

Applications

Minimum 

Application 

Interval (days)

Season/Crop or 

[Annual]

Maximum

Application Rate

(lb ai/A)

Pistachio

Ground and 

aerial spray; 

chemigation

0.125 4 14 0.5

Residential lawns

Foliar 

treatment 0.1497 1 (per year) 14 [0.1702]4

Broadcast 0.588 3 (per year) 14 NS

Rye

Ground and 

aerial 

broadcast;

chemigation; 

direct spray; 

banded

0.0997 2 6 0.1994

Soybeans

Ground and 

aerial 

broadcast;

chemigation; 

direct spray; 

banded

0.0473 3 14 0.142

0.0563 2 10 0.1126

Stone fruit

Ground and 

aerial spray; 

chemigation

0.125 3 7 0.375

Sugar beet

Ground and 

aerial 

broadcast;

chemigation; 

direct spray; 

banded

0.0997 2 14 0.1994

Seed treatment 0.0003052 NS NS NS

Sugarcane

Ground and 

aerial 

broadcast;

chemigation; 

direct spray; 

banded

0.0815 4 NS 0.3262

Tree nuts

Ground and 

aerial spray; 

chemigation

0.1094 4 7 0.4375

Triticale

Ground and 

aerial 

broadcast;

chemigation; 

direct spray; 

banded

0.082 2 6 0.1994

Seed treatment 0.00002632 NS NS NS
10

Use Method of 

Application

Maximum

Single

Application 

Rate (lb ai/A)1

Maximum 

Number of 

Applications

Minimum 

Application 

Interval (days)

Season/Crop or 

[Annual]

Maximum

Application Rate

(lb ai/A)

Wheat

Ground and 

aerial 

broadcast;

chemigation; 

direct spray; 

banded

0.0997 2 6 0.1994

Seed treatment 0.000022682 NS NS NS

NS – Not Specified

NA – Not Applicable 1 lb ai/A unless specified otherwise

2 lb ai/lb seed

3 lb ai/gallon

4 Inconsistency between single maximum application rate and annual maximum application rate given a single 

application is permitted per year.

5 lb ai/100 gallon

6 lb ai/ft2

3.3. Environmental Fate and Transport

Metconazole exists as an odorless white powdered solid at 25°C. It has a very low vapor 

pressure (1.58 ×10-10 mm Hg) which indicates that volatilization is not expected to be a 

significant route of dissipation at ambient temperatures. It is moderately soluble in water (30.4 

mg/L at 20°C), but much more soluble in organic solvents. It has a pKa value of 11.38, 

indicating that the molecule will not dissociate under neutral conditions.

Metconazole is stable to hydrolysis, aerobic aquatic metabolism, and anaerobic aquatic 

metabolism under the experimental conditions of the submitted studies. It is moderately to 

slightly degradable by direct photolysis in water. However, photodegradation in water is not 

expected to be a major route of dissipation in aquatic systems as metconazole has been shown to 

partition rapidly to the sediment (DT50 in water ranging from 1-19 days) and shown to slowly 

degrade in sediment (DT50 for the total system ranging from 140-990 days (MRID 46902205)). 

Based on three aerobic soil metabolism studies, the half-life values are in the range of 193 days 

to 630 days. In a soil photolysis study, metconazole degraded with an estimated half-life of 50-

140 days. Field dissipation studies indicate that metconazole dissipated with a DT50 ranging 

from 60 to 187 days. Adsorption/desorption studies of metconazole in four soils (pH 5.8-7.6, 

0.74-2.29 % OC) produced Koc values ranging from 1026 to 2723 ml/g. This Koc range 

suggests the chemical is slightly mobile (FAO, 2000). 

The octanol-water partition coefficient (log Kow = 3.85) suggests that metconazole has the 

potential to bioaccumulate. Bioaccumulation of metconazole was studied by exposing bluegill 

sunfish (Lepomis macrochirus) to 40 and 400 ppb of metconazole in water under flow-through 

conditions (MRID 46808425). The estimated bioconcentration factors (BCF) for edible tissue

(63-68), viscera (182-218), and whole fish (124-128) indicated a fairly low bioconcentration in 

bluegill sunfish. Depuration was rapid with DT50 of 1.5-1.7 days. 
11

Table 2 provides a summary of the physical, chemical, fate and transport characteristics of

metconazole and major degradation products. Additional details are provided in Appendix A.

 

Table 2. Environmental Fate and Transport Properties of Metconazole and Major 

Degradation Products

Parameter Value Source Comment

Metconazole

Chemical Name 5-[(4-Chlorophenyl)methyl]-2,2-dimethyl-1-(1Hl,2,4-triazol-1-ylmethyl)cyclopentanol

SMILES CC1(CCC(C1(CN2C=NC=N2)O)CC3=CC=C(C=C3)Cl)C

Structure cis-Metconazole

trans-Metconazole

Molecular Formula C17H22ON3Cl MRID 46808404

Molecular Weight 319.8 MRID 46808404

Log Kow 3.85 MRID 46808404 Flask shaking method

Aqueous Solubility (25o C) 30.4 mg/L Product Chemistry

Vapor Pressure (25o C) 1.58 ×10-10 mm Hg Product Chemistry

pKa 11.38 Product Chemistry

Henry’s Law constant 3.03 ×10-10 atm m3 mol-1 EPI Suite (v4.11)

Hydrolysis t1/2 = 0

(stable)

MRID 46808404 Stable at 120 hours

(pH 5, 7, 9)

H3C

H3C

N

N N

HO

Cl

H3C

H3C

N

N N

HO

Cl
12

Parameter Value Source Comment

Aqueous Photolysis t1/2 = 72 days 

t1/2 = 90 days 

MRID 46902202

MRID 46808405

MRID 46902202

M38 (Hydroxymetconazole) 

– 14.5%

M39 - 7.9%

MRID 46808405

M20 (1,2,4-triazole) – 6.7%

M39 – 5.2%

M38 – 3.5%

M3 (tentatively identified as 

triazole acetic acid) – 7.0%

Soil Photolysis t1/2 = 140 days 

t1/2 = 50 days 

MRID 46808406

MRID 46902203

Aerobic Soil Metabolism t1/2 = 630 days sandy loam

t1/2 = 257 days clay soil

t1/2 = 267 days sandy loam 

t1/2 = 193 days silty clay

t1/2 = 204 days sandy loam

t1/2 = 578 days sand soil

MRID 46808408

MRID 46902204

MRID 46970901

MRID 46808408 

M30 – 13% at 368days

M11 – 3.5% 

M20 (1,2,4-triazole) – 3.9%

M21 < 1%

Unidentified - 8.8%

Anaerobic Aquatic 

Metabolism 

DT50 > 120 days

DT50 > 360 days

(Stable)

MRID 46808409

MRID 46808410

Aerobic Aquatic 

Metabolism 

t1/2 = 990 days 

(Stable)

MRID 46902205 M13 – 10.9%

M11 – 3%

M15 – 2.0%

M21 – 8.0%

M30 – 7.1%

Organic Carbon Partition

Coefficient (KOC) mL/g

2723, 1115, 1026, 1312 MRID 46808411

Fish Bioconcentration BCF values: 63-68 (fillet), 

182-218 (viscera), 124-128 

(whole fish)

Depuration DT50 = 1-5 – 1.7

days

MRID 46808425

Terrestrial Field Dissipation t1/2 = 120 days

t1/2 = 60 days

t1/2 = 187 days

t1/2 = 94 days

t1/2 = 148 days

MRID 46901702

MRID 46901703

MRID 46902206

MRID 46902207

MRID 46902208

Major Degradates

M30

Chemical Name (4-Chlorophenyl) [2-hydroxy-3,3-dimethyl-2-1H1,2,4-triazol-1-ylmethyl)cyclopentanol]-methanone

Aerobic Soil Metabolism

MRID 46808408 

M30 – 13% at 368 days

SMILES CC1(CCC(C1(CN2C=NC=N2)O)CC3=CC=C(C=C3)Cl)C
13

Parameter Value Source Comment

Structure

Molecular Formula C17H20O2N3Cl EPI Suite (v4.11)

Molecular Weight 333.8 EPI Suite (v4.11)

Log Kow 2.84 EPI Suite (v4.11)

Aqueous Solubility (25o C) 29.3 mg/L EPI Suite (v4.11)

Vapor Pressure (25o C) 3.22 ×10-10 mm Hg EPI Suite (v4.11)

Koc 1950, 2630, 2884 MRID 46808412

Henry’s Law constant 3.77 ×10-13 atm m3 mol-1 EPI Suite (v4.11)

M13

Chemical Name (1S,2R,3R)-3-(p-Ch1orobenzyl)-2-hydroxy-3-methy1-

2-(1H-1,2,4-triazolylmethyl)

cyclopentanecarboxylic acid

Aerobic Aquatic Metabolism

MRID 46902205

M13 – 10.9%

SMILES C(=O)(O)C1C(O)(CN2C=NC=N2)C(Cc2ccc(Cl)cc2)CC1

Structure

Molecular Formula C16H18O3N3Cl EPI Suite (v4.11)

Molecular Weight 335.8

Log Kow 2.50

Aqueous Solubility (25o C) 136.3 mg/L

Vapor Pressure (25o C) 9.8 ×10-12 mm Hg 

Koc 151.4

Henry’s Law constant 1.28 ×10-15 atm m3 mol-1

Hydroxymetconazole (M38)

Chemical Name (4-Chlorophenyl) [2-hydroxy-3,3-dimethyl-2-1H1,2,4-triazol-1-ylmethyl)cyclopentanol]-methanone

Aqueous Photolysis

MRID 46902202

Hydroxymetconazole (M38) 

– 14.5%
14

Parameter Value Source Comment

SMILES c1cc(O)ccc1CC2CCC(C)(C)C2(O)CN3N=CN=C3

Structure 

Molecular Formula C17H23N3O2 EPI Suite (v4.11)

Molecular Weight 301.4

Log Kow 3.07

Aqueous Solubility (25o C) 109.6 mg/L

Vapor Pressure (25o C) 5.47 ×10-10 mm Hg EPI Suite (v4.11)

Koc 2543

Henry’s Law constant 4.26 ×10-14 atm m3 mol-1

Major and Minor Degradates

The degradation products of metconazole vary, depending on the specific type of degradation

(Appendix A). Aerobic soil metabolism is the major route of degradation of metconazole. In the 

soil degradation processes, M30 (13%) and CO2 were reported as the major degradates. The 

minor transformation products are M11, M20 (or 1,2,4-triazole), and M21 (MRID 46808408). 

M13 was observed as a major degradate in only one water soil system of two tested and at a level 

barely over 10% (MRID 46902205). M38 was reported as a major degradate (14.5%) and M39 

as a minor degradate in one of two aquatic photolysis studies (MRID 46902202). 

3.4. Monitoring Data

Pesticide monitoring is conducted by federal and state agencies such as the United States 

Geological Survey (USGS) National Water Quality Assessment Program (NAWQA), EPA 

repository for water quality data (STORET), and the California Environmental Data Exchange 

Network (CEDEN). Available metconazole data from these and other sources will be considered 

in the DWA and ERA.

3.5. Clean Water Act

Metconazole is not identified as a cause of impairment for any water bodies listed as impaired 

under section 303(d) of the Clean Water Act.

6

 In addition, no Total Maximum Daily Loads 

 6 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885
15

(TMDL) have been developed.

7

 The Impaired Waters and TMDL website can be consulted for 

more information.

8 Aquatic benchmarks have not been established for metconazole.9

4. Receptors

Consistent with the process described in the Overview Document (USEPA, 2004), the risk 

assessment for metconazole relies on a surrogate species approach. Toxicological data generated 

from surrogate test species, which are intended to be representative of broad taxonomic groups, 

are used to extrapolate the potential effects on a variety of species (receptors) included under 

these taxonomic groupings.

Acute and chronic toxicity data from studies submitted by pesticide registrants along with the 

available open literature will be used to evaluate the potential direct and indirect effects of 

metconazole to aquatic and terrestrial receptors. This includes toxicity on the technical grade 

active ingredient, degradates, and when available, formulated products (e.g., “Six-Pack” studies). 

Open literature studies will be identified through EPA’s ECOTOXicology (ECOTOX) 

database10, which employs a literature search engine for locating chemical toxicity data.

A summary of available toxicity data representing non-target organisms exposed to metconazole

in aquatic and terrestrial habitats is provided in Sections 4.1 and 4.2. In addition, a summary of 

residue studies is provided; these studies examined residues in pollen and nectar following 

product application. Ecological Structure Activity Relationship (ECOSAR) methods11 of the 

major degradates’ (M30, M13, and hydroxymetconazole) toxicity are discussed below and are 

presented in Appendix B. A review of ecological incidents associated with metconazole is 

provided in Section 4.3. The ECOTOX database will be searched when the risk assessment for 

metconazole is prepared. At that time, EFED will review the endpoints from open literature 

studies that are more sensitive than those from available guideline studies.

4.1. Effects to Aquatic Organisms

Table 3. Summary of Toxicity of Metconazole (TGAI)1 to Aquatic Animals

Study Type Species Toxicity Value MRID

Acute –

Freshwater Fish

Rainbow trout

(Oncorhynchus mykiss)

28-day LC50 = 1.71 (1.16-2.53)2 mg ai/L

NOAEC = 1.16 mg ai/L 

LOAEC = 2.53 mg ai/L based on mortality, 

resting on bottom of test vessel, loss of 

equilibrium, gasping, change of coloration, 

erratic swimming, and lethargy

46808424

 7

http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_

group_name=PESTICIDES

8 http://www.epa.gov/tmdl

9 http://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/aquatic-life-benchmarks-pesticideregistration/

10 http://cfpub.epa.gov/ecotox/ 11 http://www2.epa.gov/tsca-screening-tools/ecological-structure-activity-relationships-ecosar-predictive-model
16

Study Type Species Toxicity Value MRID

Acute –

Freshwater Fish

Rainbow trout

(Oncorhynchus mykiss)

96-hr LC50 = 5.4 (4.0-8.7)2 mg ai/L

NOAEC = 1.5 mg ai/L 

LOAEC = 4.0 mg ai/L based on mortality, 

darkening of color, partial to complete loss of 

equilibrium, lying on the bottom, extended 

abdomen, and ventral tearing of surface tissue

47795001

Common carp

(Cyprinodon variegatus)

96-hr LC50 = 3.3 (2.6-4.3)2 mg ai/L

NOAEC = 0.814 mg ai/L 

LOAEC = 2.02 mg ai/L based on mortality, 

lethargy, surfacing, and resting motionless on 

the bottom of the test vessel

47777001

Chronic –

Freshwater Fish

Rainbow trout

(Oncorhynchus mykiss)

NOAEC = 0.0029 mg ai/L

LOAEC = 0.009 mg ai/L based on reduced wet 

weight, dry weight, and length

46902213

Acute –

Freshwater 

Invertebrate

Water flea 

(Daphnia magna)

48-hr EC50 = 5.9 (3.8-9.3)2 mg ai/L

NOAEC = 1.5 mg ai/L 

LOAEC = 3.8 mg ai/L based on lethargy

47795002

Subchronic –

Freshwater 

Invertebrate 

(sediment)

Freshwater Midge

(Chironomus riparius)

10-day endpoints

NOAEC < 0.535 mg ai/L (pore water)

LOAEC ≤ 0.535 mg ai/L based on reduced dry 

weight

28-day endpoints

NOAEC ≥ 5.8 mg ai/L (pore water)

LOAEC > 5.8 mg ai/L based on no effects

47795006

Freshwater Amphipod

(Hyalella azteca)

NOAEC < 3.1 mg ai/L (pore water)

LOAEC ≤ 3.1 mg ai/L based on reduced dry 

weight

48937401

Chronic –

Freshwater 

Invertebrate

Water flea 

(Daphnia magna)

NOAEC = 0.031 mg ai/L

LOAEC = 0.060 mg ai/L based on reduced 

length (parents)

47795005

Acute –

Estuarine/Marine 

Fish

Sheepshead minnow 

(Cyprinodon variegates)

96-hr LC50 = 6.3 (4.6-8.5)2 mg ai/L

NOAEC = 4.6 mg ai/L 

LOAEC = 8.5 mg ai/L based on mortality. 

Loss of equilibrium was observed for about 24 

hours in test fish exposed to 4.6 mg ai/L. All 

affected fish recovered by the end of the test.

46808422

Chronic –

Estuarine/Marine 

Fish

NOAEC = 0.011 mg ai/L

LOAEC = 0.024 mg ai/L based on reduced dry 

weight and length

47795004

Acute –

Estuarine/Marine 

Mollusk

Eastern oyster 

(Crassostrea virginica)

96-hr EC50 = 2.0 (1.7-2.4)2 mg ai/L

NOAEC = 1.0 mg ai/L 

LOAEC = 2.3 mg ai/L based on reduced shell 

deposition

46808420

Acute –

Estuarine/Marine 

Invertebrate

Saltwater mysid

(Americamysis bahia)

96-hr EC50 = 0.78 (0.61-0.99)2 mg ai/L

NOAEC = 0.32 mg ai/L 

LOAEC = 0.75 mg ai/L based on mortality

46808421

Chronic –

Estuarine/Marine 

Invertebrate

NOAEC ≥ 0.059 mg ai/L

LOAEC > 0.059 mg ai/L based on no effects

48221501
17

1 Studies are based on TGAI and on an 85:15 (or close approximation) ratio mixture of cis:trans isomers. 2 Range is 95% confidence interval.

Table 4. Summary of Toxicity of Metconazole (TGAI)1 to Aquatic Plants

Study Type Species Toxicity (mg ai/L) MRID

Vascular Plant 

– Freshwater

Duckweed

(Lemna gibba)

7-day EC50 = 0.022 (0.011-0.046)2,3

Slope = 0.986±0.129

NOAEC = 0.00051

LOAEC = 0.0027 based on reduced frond number

46808428

Non-vascular 

Plant

Green algae

(Pseudokirchneriella 

subcapitata)

96-hr EC50 = 0.2 (0.15-0.27) 2,3

Slope = 3.17±0.47

NOAEC = 0.12

LOAEC = 0.21 based on reduced cell density

46808429

Freshwater diatom

(Navicula pelliculosa)

72-hr EC50 = 0.081 (0.056-0.12) 2,3

Slope = 2.51±0.35

NOAEC = 0.031

LOAEC = 0.071 based on reduced biomass

46808431

Marine diatom

(Skeletonema 

costatum)

96-hr EC50 = 1.8 (1.4-2.3) 2,3

Slope = 8.86±5.58

NOAEC = 1.1

LOAEC = 1.2 based on reduced cell density

46808432

Cyanobacteria

(Anabaena flos-aquae)

96-hr EC50 > 164

NOAEC ≥ 16

LOAEC > 16 based on no effects

47795007

1 Studies are based on TGAI and on an 85:15 (or close approximation) ratio mixture of cis:trans isomers.

2 Range is 95% confidence interval. 3 Most sensitive endpoint (based on EC50) is reported. 4 mg total ai/L because of uncertainty about exposure concentrations.

Toxicity data are not available for the major degradation products (M30, M13, and 

hydroxymetconazole).

12 Given the lack of toxicity data, ECOSAR methods were used to predict 

the aquatic toxicity of M30, M13, and hydroxymetconazole based on structural similarity to 

chemicals for which aquatic toxicity data are known. Confidence in the ECOSAR estimates is 

high because the predicted values for metconazole are between 1x (i.e., the same) and 6x of 

experimentally derived toxicity values.

13 Although degradate toxicity data (experimentally 

derived) are not available to judge confidence in the ECOSAR estimates, it is assumed that 

ECOSAR estimates of the degradates are reasonable as well given the general structural 

similarity of metconazole and the degradates. There is no evidence that M30, M13, or 

hydroxymetconazole are more toxic than metconazole. Instead, the ECOSAR estimates suggest 

that M30 and hydroxymetconazole are similar in toxicity to metconazole (estimates are up to 

40X different than empirically derived metconazole toxicity data but most are within one order 

of magnitude). M13 toxicity estimates suggest that it may be less toxic than metconazole, M30, 

and hydroxymetconazole (most estimates are two orders of magnitude less toxic than empirically 

derived metconazole toxicity data). ECOSAR estimates are presented in Appendix B.

 12 Toxicity data for two minor degradates (1,2,4-triazole and triazole acetic acid) were reported in a recent 

registration review problem formulation for difenoconazole (see USEPA, 2015b) and are not repeated here. 13 All comparisons here forward are based on the ECOSAR class showing the greatest toxicity 
18

4.2. Effects to Terrestrial Organisms

Table 5. Summary of Toxicity of Metconazole (TGAI)1 to Terrestrial Organisms

Study Type Species Toxicity Value MRID

Acute – Avian 

Oral Dose

Northern Bobwhite 

Quail 

(Colinus virginianus)

LD50 = 777 (671-900)2 mg ai/kg-bw 3,4

NOAEL < 441 mg ai/kg-bw

LOAEL ≤ 441 based on body weight loss (male and 

female), reduced food consumption (male), and 

clinical signs of toxicity (male and female)

46808413

Acute – Avian 

Dietary

LC50 = 1078 (743-1562)2 mg ai/kg diet

NOAEC < 165 mg ai/kg diet

LOAEC ≤ 165 mg ai/kg diet based on reduced body 

weight gain

46808414

Acute – Avian 

Dietary

Mallard Duck 

(Anas platyrhynchos)

LC50 >5230 mg ai/kg diet

NOAEC = 1370 mg ai/kg diet

LOAEC = 2540 mg ai/kg diet based on reduced 

food consumption and body weight gain

46808415

Chronic –

Avian Dietary

Northern Bobwhite 

Quail 

(Colinus virginianus)

NOAEC = 58 mg ai/kg diet

LOAEC = 114 mg ai/kg diet based on significant 

reduction in live 3-week embryos, hatching success, 

chick survival, chick body weights, and adult 

female body weight gain

46808416

Mallard Duck 

(Anas platyrhynchos)

NOAEC = 120 mg ai/kg diet 

LOAEC = 247 mg ai/kg diet based on significant 

reduction in ratio of eggs not cracked/eggs laid

46808417

Acute –

Mammalian 

Oral Dose

Laboratory rat 

(Rattus norvegicus)

LD50 = 595 mg ai/kg bw (female)5,6 44721512

Chronic –

Mammalian 

Two 

Generation 

Reproduction

NOAEC = 150 mg ai/kg diet7,8

LOAEC = 750 mg ai/kg diet based on parental

(decreased body weight and weight gain, increased 

incidence of fatty hepatocyte change in males, and 

increased incidence of spleen congestion in F1 

females), reproduction (increased gestation length 

and dystocia), and offspring (decreased viability on 

lactation day 0 and decreased body weight in F2

offspring) effects

46808447

Acute – 

Terrestrial 

Invertebrate

Contact

Earthworm 

(Eisenia foetida)

LC50 > 952 mg ai/kg substrate9

NOAEC ≥ 952 mg ai/kg substrate

LOAEC > 952 mg ai/kg substrate based on no 

effects

46808427

Acute –

Terrestrial 

Invertebrate 

Contact and 

Oral

Adult honey bee 

(Apis mellifera)

Test material - TGAI

Acute Oral Toxicity

LC50 = 88 (61-130)2 μg ai/bee

NOAEC = 11 μg ai/bee

LOAEC = 24 μg ai/bee based on mortality

Acute Contact Toxicity

LD50 > 95.3 μg ai/bee

NOAEL ≥ 95.3 μg ai/bee

LOAEL > 95.3μg ai/bee based on no effects

46808426
19

Study Type Species Toxicity Value MRID

Acute –

Terrestrial 

Invertebrate 

Contact and 

Oral

Adult honey bee 

(Apis mellifera)

Test material – TEP: BAS 556 02 F (13.34 % 

pyraclostrobin; 5.03% metconazole)

Acute Oral Toxicity

LC50 = 76.6 μg formulation/bee

LC50 = 3.85 μg metconazole/bee

NOAEC = 1.67 μg metconazole/bee

LOAEC = 3.35 μg metconazole/bee based on 

mortality and impaired locomotion at the 4-hour 

observation interval; however, the behavioral effect 

was transient

Acute Contact Toxicity

LD50 > 532.5 μg formulation/bee

LD50 > 26.8 μg metconazole/bee

NOAEL = 6.69 μg metconazole/bee

LOAEL = 13.4 μg metconazole/bee based on 

mortality and impaired locomotion at the 4-hour 

observation interval; however, the behavioral effect 

was transient

49525001

Test material – TEP: BAS 556 01 F (12.5 % 

pyraclostrobin; 7.32% metconazole)

Acute Oral Toxicity

LC50 = 21.5 μg formulation/bee

LC50 = 1.6 (1.3-1.9)2 μg metconazole/bee

NOAEC = 0.7 μg metconazole/bee

LOAEC = 1.3 μg metconazole/bee based on 

mortality and behavioral effects (coordination 

problems and apathy); however, the behavioral

effects were transient

48202006

1 Studies are based on TGAI and on an 85:15 (or close approximation) ratio mixture of cis:trans isomers unless 

indicated otherwise.

2 Range is 95% confidence interval.

3 Based on an 85:15 ratio mixture of cis:trans isomers. 4 LD50 = 839 mg ai/kg bw based on 95% cis isomer (also MRID 46808413). NOAEL < 435 mg ai/kg bw and 

LOAEL ≤ 435 based on mortality, body weight loss (male and female), and clinical signs of toxicity (male and 

female). 5 Based on an 85:15 ratio mixture of cis:trans isomers. 6 The LD50 = 1312 mg ai/kg-bw (female) based on 95% cis isomer (MRID 44721513). Both studies (85:15 cis:trans 

mixture and 95% cis isomer) showed similar clinical signs of toxicity and some signs were noted at all test 

concentrations. Typical effects in both studies were diarrhea, abasia, ataxia, salivation, body weight loss, 

prostration, lethargy, piloerection, tremor and convulsion, and coma. 7 Based on an 85:15 ratio mixture of cis:trans isomers. Toxicity expressed on a dose equivalent basis was NOAEL = 

9.79 (male) and 10.78 (female) mg ai/kg-bw and LOAEL = 49.4 (male) and 53.2 (female) mg ai/kg-bw. 8 NOAEL = 8 mg ai/kg-bw and LOAEL = 32 mg ai/kg-bw (effects to parents and reproduction) based on 95% cis 

isomer (MRID 44721608). Offspring NOAEL = 32 mg ai/kg-bw and LOAEL = 48 mg ai/kg-bw. 9 Based on 95% cis isomer. 
20

Table 6. Summary of Toxicity of Metconazole (Formulations) to Terrestrial Plants

Study Type Species Test Material 

(% ai)

Toxicity (lb ai/A) MRID

Seedling 

Emergence 

(Tier II)

Corn, Onion, 

Ryegrass, Wheat, 

Buckwheat, Flax, 

Radish, Lettuce, 

Soybean, and 

Tomato

Metconazole 

50 WDG 

(51.3)

Monocot

EC25 > 0.60 based on all test species

NOAEC = 0.30

LOAEC = 0.60 based on ryegrass 

reduced height and corn reduced dry 

weight and height

Dicot

EC25 = 0.15 (0.085-0.25)1 based on 

radish reduced height

NOAEC = 0.075

LOAEC = 0.15

46805103

Corn, Onion, 

Ryegrass, Wheat, 

Radish, Cabbage, 

Lettuce, Bean, 

Soybean, and 

Tomato

Caramba: BAS 

555 01 F

(8.4)

Monocot

EC25 > 0.097/0.0982

NOAEC ≥ 0.097/0.098

LOAEC > 0.097/0.098 based on no 

effects (all test species)

Dicot

EC25 > 0.097/0.0982 based on all test 

species

NOAEC = 0.032

LOAEC = 0.097 (cabbage)/0.098 

(radish) based on reduced height

46902214

Vegetative 

Vigor

(Tier II)

Corn, Onion, 

Ryegrass, Wheat, 

Buckwheat, Flax, 

Radish, Lettuce, 

Soybean, and 

Tomato

Metconazole 

50 WDG 

(51.3)

Monocot

EC25 > 0.60

NOAEC ≥ 0.60

LOAEC > 0.60 based on no effects (all 

test species)

Dicot

EC25 = 0.44 (0.11-1.8)1 based on 

radish reduced shoot dry weight

EC05 = 0.0036 (0.000054-0.23)1

NOAEC < 0.038

LOAEC ≤ 0.038

46805104
21

Study Type Species Test Material 

(% ai)

Toxicity (lb ai/A) MRID

Vegetative 

Vigor

(Tier II)

Corn, Onion, 

Ryegrass, Wheat, 

Radish, Cabbage, 

Lettuce, Bean, 

Soybean, and 

Tomato

Caramba: BAS 

555 01 F

(8.4)

Monocot

EC25 > 0.097/0.102

NOAEC ≥ 0.097/0.10

LOAEC > 0.097/0.10 based on no 

effects (all test species)

Dicot

EC25 > 0.097/0.102 based on all test 

species

NOAEC = 0.006

LOAEC = 0.012 based on reduced 

radish dry weight

46902215

1 Range is 95% confidence interval.

2 Some species were exposed to a maximum concentration of 0.097 lb ai/A and others were exposed to 0.098 lb ai/A

or 0.1 lb ai/A.

Table 7. Residues in Pollen and Nectar

Study Type Species Test Material Residues MRID

Single 

Application -

Field

Sunflower

(Helianthus 

annuus)

BAS 556 03F

(13% pyraclostrobin; 

8% metconazole)

Maximum Pyraclostrobin Residues

Nectar = 0.53 mg/kg

Pollen = 17.00 mg/kg

Flower heads = 1.50 mg/kg

Maximum Metconazole Residues

Nectar = 0.33 mg/kg

Pollen = 11.00 mg/kg

Flower heads = 0.81 mg/kg

49459604

Oilseed rape

(Brassica 

napus)

BAS 556 03F

(13% pyraclostrobin; 

8% metconazole)

Maximum Pyraclostrobin Residues

Nectar = 0.231 mg/kg

Pollen = 7.787 mg/kg

Flowers = 20.994 mg/kg

Maximum Metconazole Residues

Nectar = 0.305 mg/kg

Pollen = 4.582 mg/kg

Flowers = 21.314 mg/kg

49459605

4.3. Incident Databases Review

Reviews were conducted of the Ecological Incident Information System (EIIS, version 2.1.1)14, 

the Agency’s Aggregated Incidents Reports database, and the Avian Incident Monitoring System 

(AIMS)15 on 9/28/2015.

16 No incidents involving metconazole were reported in the Aggregated 

Incidents Reports database or AIMS. There are three incidents reported in EIIS associated with 

 14 http://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/technical-overview-ecological-riskassessment-risk 15 http://www.abcbirds.org/abcprograms/policy/toxins/aims/aims/index.cfm 16 The AIMS database was not accessible on September 28, 2015. No incidents were reported when it was last 

accessed on September 16, 2014.
22

potential exposure to metconazole; however, in each case it is likely that the observed effects 

were primarily due to exposure to other chemicals. Sugar beet mortality was observed in one 

incident after potential exposure to metconazole, pyraclostrobin, and two herbicides (MCPA and 

fluroxypyr meptyl). Honeybee mortality was observed in two separate incidents after possible 

exposure to metconazole and pyraclostrobin; however, in one case an insecticide (clothianidin) 

was detected in bee tissue and in the other case bees may have been exposed to two insecticides 

(fenpropathrin and imidacloprid).

The total number of actual incidents associated with the use of metconazole may be higher than 

what is reported to the Agency. Incidents may go unreported since effects may not be 

immediately apparent or readily attributed to the use of a chemical. As such, the absence of 

incident reports cannot be construed as the absence of incidents.

5. Exposure Pathways of Concern

The use patterns and environmental fate properties of metconazole indicate that exposure to nontarget aquatic and terrestrial organisms may occur from direct spray and offsite movement via 

spray drift and runoff.

An additional exposure pathway that will be considered is the consumption of contaminated fish 

by piscivorus animals. It is not anticipated to be a major exposure pathway for metconazole; 

however, it will be considered given that fate data (log Kow) of metconazole (3.85) suggests that 

metconazole may bioaccumulate to some degree in the aquatic food web and because 

metconazole is expected to be persistent.

17

Screening Imbibition Program

The Screening Imbibition Program (SIP v.1.0)18 was used to calculate an upper bound estimate 

of bird and mammal exposure to metconazole in drinking water. Drinking water exposure alone 

was determined not to be an acute or chronic concern for mammals nor an acute concern for 

birds. However, the screen suggests that there is a potential chronic concern for birds. Appendix 

C provides model results.

Screening Tool for Inhalation Risk 

The Screening Tool for Inhalation Risk (STIR v.1.0)18 was used to provide an upper bound 

estimate of exposure of birds and mammals to pesticides through inhalation of spray drift or 

vapor. The screening suggests that metconazole exposure via inhalation alone is not likely 

significant enough for an inhalation risk concern. Appendix D provides model results.

 17 Bioaccumulation potential is assumed to increase with increasing log Kow. Current guidance is to assess 

bioaccumulation potential for chemicals meeting certain criteria including a log Kow between 4 and 8. Although 

the mean log Kow (3.85) for metconazole is less than 4, the value is from a single study conducted under specific 

conditions and is close to the lower end criterion of log Kow = 4. Furthermore, metconazole is expected to be 

persistent and accumulate in the environment; therefore, residues in fish may increase over time, especially in static 

systems, to the extent that bioaccumulation occurs.

18 http://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/models-pesticide-risk-assessment
23

6. Analysis Plan

In order to address the risk hypothesis, the potential for adverse effects on the environment is 

estimated. The use, environmental fate, and ecological effects of metconazole will be 

characterized and integrated to assess risk. This will be accomplished using an RQ approach 

(i.e., ratio of exposure concentration to effects concentration). Although risk is often defined as 

the likelihood and magnitude of adverse ecological effects, the risk quotient-based approach does 

not provide a quantitative estimate of likelihood or magnitude of an adverse effect. However, as 

outlined in the Overview Document (USEPA, 2004), the likelihood of effects to individual 

organisms from particular uses of metconazole will be estimated using the probit dose-response 

slope and either the level of concern or actual calculated risk quotient value.

This analysis plan will be revisited and may be revised depending upon a full review of the data 

available in the open literature and the information submitted by the public in response to the 

opening of the Registration Review docket.

6.1. Stressors of Concern

Ecological Risk Assessment

Metconazole will be considered the stressor of concern in the ecological risk assessment. In 

general, the degradates are not expected to contribute substantially to exposure or modify risk 

conclusions in part because metconazole is slow to degrade in the environment. Although M30 

was a major degradate in an aerobic soil laboratory study (up to 13% of the applied dose), a 

previous assessment concluded that risk conclusions would not change if M30 were included in 

the exposure estimates (USEPA, 2011). Hydroxymetconazole is likely equal in toxicity to 

metconazole and was a major aqueous photolysis product (up to 15% of the applied dose). 

However, photolysis is not likely to be a significant route of dissipation in the environment for 

registered uses, thus inclusion of hydroxymetconazole is not likely to substantially change 

exposure estimates. M13 was observed as a major degradate (barely over 10%) only in one 

water soil system and it may be less toxic than metconazole; therefore, it is not considered to be 

a stressor of concern.

Although metconazole will be the focus of the risk assessment, M30 and possibly 

hydroxymetconazole could be included as stressors of concern on a case-by-case basis if 

refinements are needed given that ECOSAR estimates suggest that they are likely similar to 

metconazole in toxicity. Inclusion of these degradates may slightly reduce the number of crop 

seasons or years of residue accumulation that are required before metconazole use becomes a 

risk concern to certain aquatic organisms. 

Drinking Water Assessment

Metconazole will be considered the stressor of concern in the metconazole DWA, consistent with 

the recommendations of the Residue of Concern Knowledgebase Subcommittee (ROCKS) 

(USEPA, 2008).
24

Aggregate Risk Assessment

Aggregate risk from two of the minor degradates, 1,2,4-triazole and its conjugate: triazole acetic 

acid, may be addressed in a separate ERA and DWA because they are common to the class of 

compounds known as triazoles (i.e., triazole-derivative fungicides, T-D fungicides, or 

conazoles).

6.2. Measures of Exposure

Metconazole concentrations in aquatic and terrestrial environments will be modeled using the 

maximum labeled application rates, the maximum number of applications, the minimum reapplication intervals, and application methods that have the greatest potential for off-site 

transport. 

Aquatic Exposure 

There is potential for exposure to non-target organisms through run-off and spray drift. The 

most current models will be used to estimate residues in water at the time of the risk assessment 

(e.g., Pesticide in Water Calculator (PWC)).19 Bioaccumulation potential in aquatic organisms 

will be estimated to assess exposure to piscivorus animals (e.g., Kow (based) Aquatic 

BioAccumulation Model (KABAM))19 given that the available fate data of metconazole (log 

Kow = 3.85) suggests some potential for bioaccumulation and because metconazole is persistent.

Terrestrial Exposure

There is potential for exposure to non-target organisms through consumption of contaminated 

food items (e.g., treated insects or vegetation and perhaps contaminated fish), direct application, 

runoff, or spray drift. The most current models will be used at the time of the risk assessment. 

Current models include:

T-REX (v 1.5.2)

19 is used to estimate avian and mammal exposure to metconazole. For input 

into T-REX, the default foliar dissipation DT50 of 35 days will be used in the absence of 

acceptable foliar dissipation rate data.

TerrPlant (v 1.2.2)19 is used to calculate EECs for characterizing exposure to terrestrial and semiaquatic plants.

Terrestrial Investigation Model (TIM, v. 3.0 beta)19 is used to derive quantitative estimates of the 

probability (or likelihood) and magnitude of bird mortality.

6.3. Measures of Effect

Toxicity effects data will be used as measures of direct and indirect effects to biological 

receptors (USEPA, 2004). As discussed previously, data will be obtained from registrantsubmitted studies and from literature studies identified in ECOTOX.

 19 http://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/models-pesticide-risk-assessment
25

Quantitative assessment of risks will be based on study endpoints that can be directly linked to 

the Agency’s assessment endpoints of impaired survival, growth, and reproduction. Sub-lethal 

effects (e.g., lethargy and changes in coloration) will be evaluated qualitatively. Available 

incident data will be used to further characterize risk.

6.4. Integration of Exposure and Effects

The exposure and effects data will be integrated in order to evaluate potential adverse ecological 

effects on non-target species. The risk quotient method will be used to compare exposure and 

measured toxicity values. EECs will be divided by acute and chronic toxicity values. The 

resulting RQs will be compared to the Agency’s LOC (USEPA, 2004). 

6.5. 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 report20 outlines 

recommendations on specific scientific and technical issues related to the development of 

pesticide risk assessments that EPA and the Services (U.S. Fish and Wildlife Service and 

National Marine Fisheries) must conduct in connection with their obligations under the ESA and 

FIFRA. EPA will address concerns specific to metconazole in connection with the development 

of its final registration review decision for metconazole. 

In November 2013, EPA, 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. 21

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 metconazole 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 metconazole 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 

 20 http://www.nap.edu/catalog/18344/assessing-risks-to-endangered-and-threatened-species-from-pesticides 21 http://www2.epa.gov/endangered-species/interim-approaches-pesticide-endangered-species-act-assessmentsbased-nas-report
26

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 metconazole as part of completing this registration review.

6.6. Endocrine Disruptor Screening

As required by Federal Food, Drug and Cosmetic Act (FFDCA) section 408(p), metconazole is 

subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

22 

Metconazole was not included in the first group of pesticide active ingredients that were required 

to undergo Tier 1 EDSP testing. 

6.7. Drinking Water Assessment

A DWA will be conducted to support future human health dietary risk assessments, if warranted. 

The residue of concern will be metconazole only as recommended by the ROCKS committee 

(USEPA, 2008). Concentrations in surface and groundwater will be estimated using current 

guidance and models.23 Additionally, EFED may update the previously conducted aggregate 

drinking water exposure assessment for 1,2,4-triazole and its conjugates.

6.8. Preliminary Identification of Data Gaps

Available studies submitted to fulfill environmental fate and ecological effects guideline 

requirements, as well as outstanding data gaps for metconazole are defined in Sections 6.8.1 and 

6.8.2, respectively. Studies are identified that offer data for each guideline requirement, as well 

as study classifications and whether or not further data are needed in order to support the risk

assessment.

6.8.1. Environmental Fate Data

The available environmental fate data for metconazole are adequate for conducting a risk 

assessment; however, an ECM/ILV is needed for monitoring metconazole residues in water 

(Table 8). EFED does not recommend requesting environmental fate data for any of the major 

degradates (M30, M13, and hydroxymetconazole) at this time.

EFED recommends requesting the following study to reduce uncertainty in the risk assessment:

• 850.6100: Environmental chemistry method and independent laboratory validation 

(ECM/ILV) reports for analytical method in water (metconazole; TGAI; LOQ <3 μg/L)

Table 8. Environmental Fate Data Requirements for Metconazole and Data Gaps

Guideline Description MRID Classification Data 

Gap? Comments

Metconazole

835.2120 Hydrolysis 46808404

46902201

Acceptable

Acceptable No -

 22 http://www2.epa.gov/endocrine-disruption 23 http://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/models-pesticide-risk-assessment
27

Guideline Description MRID Classification Data 

Gap? Comments

835.2240 Aqueous photolysis 46808405

46902202

Supplemental

Acceptable No -

835.2410 Soil photolysis 46808406

46902203

Acceptable

Acceptable No -

835.4100 Aerobic soil metabolism

46808408

46902204

46970901

Acceptable

Supplemental

Supplemental

No -

835.4300 Aerobic aquatic metabolism 46902205 Acceptable No -

835.4200

835.4400

Anaerobic soil/Aquatic 

metabolism

46808409 Supplemental

No - 46808410 Acceptable

835.1230

835.1240

Adsorption/desorption and 

leaching 46808411 Supplemental No -

835.6100 Terrestrial field dissipation

46901702

46901703

46902206

46902207

46902208

Acceptable

Acceptable

Acceptable

Acceptable

Acceptable

No -

850.6100

ECM/ILV soil 46902209

46902210 Supplemental No

-

ECM/ILV water - - Yes

850.1730 Fish bioconcentration 46808425 Acceptable No -

M30

835.1230

835.1240

Adsorption/ desorption and 

leaching 46808412 Supplemental No

BOLD = Recommended Studies

6.8.2. Ecological Effects Data

Data gaps for metconazole remain (Tables 9, 10, 11, and 12); however, some of these studies 

are anticipated to have little impact on the risk assessment and are not recommended for DCI. 

EFED recommends requesting the following studies to reduce uncertainty in the risk assessment: 

• 850.2100: Avian oral toxicity (passerine species) (metconazole; TGAI)

• Non-guideline: Chronic toxicity to benthic invertebrates (whole sediment, three test 

species: freshwater amphipod, freshwater midge, and estuarine/marine amphipod) –

(metconazole; TGAI)
28

o EFED recommends that the registrant consider Agency-wide guidelines for 

chronic testing of freshwater and estuarine/marine organisms24,25 because the 850 

guidelines are in the process of being finalized. A protocol must be submitted for 

review prior to initiating the studies.

o The study design of the chronic studies could be modified to address the 

unexplained effects on growth observed in the available subchronic tests in lieu of 

additional subchronic testing on the freshwater midge and amphipod. 

• Non-guideline (Tier I): Honeybee adult chronic oral exposure (metconazole; TGAI)

• Non-guideline (Tier I): Honeybee larval acute and chronic oral exposure (metconazole; 

TGAI)

• Non-guideline (Tier II): Residue in pollen and nectar (recommendation pending risks 

identified in Tier I studies) (TEP)

• 850.3040 (Tier II): Semi-field testing for pollinators (tunnel and feeding studies) 

(recommendation pending risks identified in Tier I studies) (TEP)

• 850.3040 (Tier III): Full-field testing for pollinators (recommendation pending risk 

identified in Tier II studies) (TEP)

Toxicity data from other sources (e.g., other conazoles) may be used in the absence of data for 

metconazole. Use of surrogate data may over or underestimate risk of metconazole use.

Major degradates (M30, M13, and hydroxymetconazole)

EFED does not recommend requesting toxicity data for any of the major degradates at this time. 

ECOSAR estimates suggest that M30, hydroxymetconazole, and metconazole are of similar 

toxicity and that M13 may be less toxic. EFED is not aware of any evidence that these 

degradates may be more toxic than metconazole. A previous assessment concluded that risk 

conclusions would not change if M30 were included in the exposure estimates (USEPA, 2011). 

This is primarily due to the persistence of metconazole. However, inclusion of the degradates 

(M30 and perhaps hydroxymetconazole) may slightly reduce the number of years it would take 

for the residues to accumulate before metconazole use becomes a risk concern to some aquatic 

organisms. Although data are not requested, future risk assessments may incorporate M30 and 

hydroxymetconazole on a case-by-case basis by using a total toxic residue (TTR) approach to 

calculate EECs and assume that the degradates and metconazole are of equal toxicity.

Whole Sediment Acute and Chronic Toxicity (Freshwater and Marine Invertebrates) 

Chronic whole sediment toxicity studies are a data gap for metconazole and testing with three 

species is recommended: freshwater midge, freshwater amphipod, and marine/estuarine 

amphipod. Two subchronic tests (freshwater midge and freshwater amphipod) are available; 

however, the need for chronic testing cannot be discounted based on the results from those

studies. Both tests, which were independently conducted, resulted in non-definitive endpoints 

due to unexplained effects on dry weight at the lowest test concentrations. Furthermore, past risk 

 24 USEPA 2000. Methods for Measuring the Toxicity and Bioaccumulation of Sediment-associated Contaminants 

with Freshwater Invertebrates. EPA 600/R-99/064. http://www.epa.gov/nscep 25 USEPA 2001. Methods for Assessing the Chronic Toxicity of Marine and Estuarine Sediment-associated 

Contaminants with the Amphipod Leptocheirus plumulosus. EPA 600/R-01/020. http://www.epa.gov/nscep
29

assessments indicated a chronic concern for water column invertebrates (freshwater and marineestuarine invertebrates) while acute concerns were less common. The potential for a chronic risk 

concern for benthic invertebrates is also supported by the exceedance of the chronic LOC (1.0) 

based on comparison of water column chronic toxicity data (water column species) to benthic

(i.e., pore water) EECs.26 

Even with submission of chronic testing, the effects on dry weight in the available subchronic

studies would remain an uncertainty. To address this uncertainty, EFED recommends including 

dry weight in the study design of the chronic studies rather than conducting additional 

subchronic testing. The test concentrations should be relevant to those showing effects in the 

available subchronic tests (i.e., testing should include concentrations above and below the 

concentrations showing dry weight effects in the subchronic studies). EFED recommends that 

the registrant consider Agency-wide guidelines for chronic testing of freshwater and 

estuarine/marine organisms27,28 because the 850 guidelines are in the process of being finalized. 

A protocol must be submitted for review prior to initiating the studies.

Chronic toxicity data from other sources will be used for risk assessment (e.g., water column 

invertebrate data for metconazole or benthic invertebrate data for other conazoles) in the absence 

of chronic metconazole toxicity data for benthic invertebrates. Use of surrogate data may over or 

underestimate risk of metconazole use.

Table 9. Ecological Effects Data Requirements (TGAI) for Aquatic Organisms Exposed to 

Metconazole and Data GapsA

Guideline Description MRID Classification Data 

Gap? Comments

850.1075

Acute freshwater fish 

toxicity

(cold water species)

47795001 Acceptable 

No

1 Study is not recommended at 

this time as additional data are 

unlikely to have substantial 

impact on the risk assessment. 

2 Not technically a data gap 

because chronic studies are 

required due to the persistence 

of metconazole. However, 

there are unexplained effects in 

the available studies that should 

be further addressed to reduce 

uncertainty (see suggested 

approach in text above).

3 See text above (Section 6.8.2) 

for detailed explanation of data 

recommendations. 

46808424

Supplemental

(OECD 204 

study – 28 

days)

850.1075

Acute freshwater fish 

toxicity

(warm water species)

47777001 Acceptable No

Acute estuarine/

marine fish toxicity 46808422 Acceptable No

850.1010

Acute toxicity to 

freshwater 

invertebrates

47795002 Acceptable No

850.1025

Acute estuarine/

marine mollusk 

toxicity

46808420 Acceptable No

 26 For example, porewater 21-day EEC for corn (112 μg/l; USEPA, 2011) / daphnia NOAEC (31 μg/l) = 3.6 27 USEPA 2000. Methods for Measuring the Toxicity and Bioaccumulation of Sediment-associated Contaminants 

with Freshwater Invertebrates. EPA 600/R-99/064. http://www.epa.gov/nscep 28 USEPA 2001. Methods for Assessing the Chronic Toxicity of Marine and Estuarine Sediment-associated 

Contaminants with the Amphipod Leptocheirus plumulosus. EPA 600/R-01/020. http://www.epa.gov/nscep
30

Guideline Description MRID Classification Data 

Gap? Comments

850.1035

Acute estuarine/

marine invertebrate

toxicity

46808421 Supplemental Yes1

4 Study endpoints are under rereview. A new study is not 

recommended.

5 There is some uncertainty 

about the bioavailable exposure 

concentration. A new study is 

not recommended at this time 

because additional data are 

unlikely to impact risk 

conclusions.

850.1300 Freshwater 

invertebrate life cycle 47795005 Acceptable No

850.1350 Saltwater invertebrate 

life cycle 48221501 Acceptable No

850.1400

Freshwater fish early 

life stage 46902213 Acceptable No

Saltwater fish early life 

stage 47795004 Acceptable No

850.1735

Whole sediment acute 

toxicity, freshwater 

invertebrates

47795006

48937401

Supplemental

Supplemental Yes2,3

850.1740

Whole sediment acute 

toxicity, marine 

invertebrates

- - No

-

Whole sediment 

chronic toxicity, 

freshwater 

invertebrates

- - Yes3

-

Whole sediment 

chronic toxicity, 

marine-estuarine 

invertebrates

- - Yes3

850.5400B

Aquatic plant growth

(freshwater green 

alga)

46808429 Supplemental4 Yes4

Aquatic plant growth 

(freshwater diatom) 46808431 Supplemental4 Yes4

Aquatic plant growth 

(saltwater diatom) 46808432 Supplemental4 Yes4

850.5400B Aquatic plant growth 

(Cyanobacteria) 47795007 Supplemental Yes5

850.4400B Aquatic plant growth 

(vascular plants) 46808428 Acceptable No

A Several invalid studies were previously submitted [acute toxicity to fish (MRID 46808419 and 46808418), acute 

toxicity to freshwater invertebrates (MRID 46808418), chronic toxicity to freshwater invertebrates (MRID 

46902212), chronic toxicity to marine/estuarine invertebrates (MRID 46808423), toxicity to freshwater algae 

(MRID 46808418), and cyanobacteria (MRID 46808430)] but were subsequently replaced with valid studies. BAs of July 2012 the new guideline numbers are 850.4500 (Algal toxicity) and 850.4550 (Cyanobacteria toxicity)

BOLD = Recommended Studies
31

Table 10. Ecological Effects Data Requirements (TGAI) for Terrestrial Animals Exposed 

to Metconazole and Data Gaps

Guideline Description MRID Classification Data 

Gap?

Comments

850.2100

Avian acute oral 

toxicity

(upland game or 

waterfowl species)

46808413 Acceptable No

1 Data are needed to assess risk 

because an exposure pathway 

exists, some of the registered 

uses are pollinator attractive 

crops (USDA, 2015), and 

incidental residues may occur on 

non-crop flowering plants (e.g.,

weeds) on or near the treatment 

site.

2 If Tier 1 screening risks are 

identified based on Tier I toxicity 

studies then Tier II studies 

(residue in pollen and nectar and 

semi-field testing for pollinators) 

could be recommended and if 

risks are identified based on a 

Tier II assessment then Tier III 

studies could be recommended 

(850.3040 full-field testing for 

pollinators).

Avian acute oral 

toxicity 

(passerine species)

- - Yes

850.2200

Avian dietary toxicity 

(upland game species) 46808414 Acceptable No

Avian dietary toxicity 

(waterfowl species) 46808415 Acceptable No

850.2300

Avian reproduction 

(upland game species) 46808416 Acceptable No

Avian reproduction 

(waterfowl species) 46808417 Acceptable No

850.3020

Adult honeybee acute 

contact and oral 

toxicity (Tier 1)

46808426

Acceptable 

(oral study is 

Supplemental)

No

Nonguideline

Adult honeybee 

chronic oral toxicity 

(Tier 1)

- - Yes1,2

Nonguideline

Larval honeybee acute 

and chronic oral 

toxicity (Tier 1)

- - Yes1,2

BOLD = Recommended Studies

Table 11. Ecological Effects Data Requirements (TEP) for Metconazole Residues in Pollen 

and Nectar, Semi-Field/Full-Field Testing for Pollinators, and Data Gaps

Guideline Description MRID Classification Data 

Gap?

Comments

Nonguideline

Semi-field testing for 

pollinators (tunnel and 

feeding studies) 

(Tier II)

- - Yes1

1 Recommendations for Tier II 

testing are pending results of Tier 

I screening of honeybee risk and 

recommendations for Tier III 

testing would be based on if risk 

is identified in Tier II testing (see 

Table 10). 

2 Additional testing could 

potentially be recommended on 

different plant species or 

different TEPs.

850.3040

Full-field testing for 

pollinators 

(Tier III)

- - Yes1

Nonguideline

Residues in Pollen and 

Nectar (Tier II 

honeybee testing)

49459604

49459605

Supplemental

Supplemental Yes1,2

BOLD = Recommended Studies
32

Table 12. Ecological Effects Data Requirements (TEP) for Plants Exposed to Metconazole

and Data Gaps

Guideline Description MRID Classification Data 

Gap? Comments

850.4100A

Terrestrial plant 

toxicity (Tier I or Tier 

II seedling emergence)

46805103

46902214

Acceptable

Acceptable No

850.4150B

Terrestrial plant 

toxicity (Tier I or Tier 

II vegetative vigor)

46805104

46902215

Acceptable

Acceptable No

A As of July 2012 the Final Guideline 850.4100 contains both Tier I and Tier II test guidance.

B As of July 2012 the Final Guideline 850.4150 contains both Tier I and Tier II test guidance.

7. References

FAO. 2000. Appendix 2. Parameters of pesticides that influence processes in the soil. In FAO 

Information Division Editorial Group (Ed.), Pesticide Disposal Series 8. Assessing Soil 

Contamination. A Reference Manual. Rome: Food & Agriculture Organization of the 

United Nations (FAO). http://www.fao.org/docrep/003/x2570e/x2570e00.htm

USDA. 2015. Attractiveness of Agricultural Crops to Pollinating Bees for the Collection of 

Nectar and/or Pollen.

USEPA. 2004. Overview of the Ecological Risk Assessment Process in the Office of Pesticide 

Programs. U.S. Environmental Protection Agency, Office of Prevention, Pesticides and 

Toxic Substances, Office of Pesticide Programs, Washington DC. January 23, 2004.

USEPA. 2008. Metconazole. Report of the Residues of Concern Knowledgebase 

Subcommittee. U.S. Environmental Protection Agency, Office of Pesticide Programs, 

Health Effects Division. DP 348234. 

USEPA. 2011. Ecological Risk Assessment for the Proposed New Use of Metconazole on 

Sugarcane, and Proposed Low Volume Aerial Applications of Metconazole on 

Registered Corn, Triticale, and Wheat. Office of Pesticide Programs, Environmental Fate 

and Effects Division. DP 386426+.

USEPA. 2014a. Ecological Risk Assessment to Support the Proposed Section 3 New Use of 

Metconazole 50 WDG Fungicide on Dried Shelled Pea, Beans, Sunflower and the 

Amended Crop Groupings of Stone Fruit Group 12-12, Tree Nuts (14-12), and the 

Expansion of Canola to Rapeseed Subgroup 20A-Uses. Office of Pesticide Programs, 

Environmental Fate and Effects Division. DP 418957+.

USEPA. 2014b. Drinking Water Exposure Assessment for the Section 3 New Use of 

Metconazole on Pea and Bean (Dried Shelled, Subgroup 6C) and Sunflower (Subgroup 

20B). Office of Pesticide Programs, Environmental Fate and Effects Division. DP 

418674.
33

USEPA. 2015a. Metconazole (125619) Label Reports Package in Support of Registration 

Review. Office of Pesticide Programs, Biological and Economic Analysis Division. 

March 31, 2015.

USEPA. 2015b. Difenoconazole: Preliminary Problem Formulation for Environmental Fate, 

Ecological Risk, Endangered Species, and Drinking Water Exposure Assessments in 

Support of Registration Review. Office of Pesticide Programs, Environmental Fate and 

Effects Division. DP 428500.
34

APPENDIX A. Metconazole and its Environmental Degradates

Table A-1

Code Name

(Synonym) Chemical Name Chemical Structure Study Type MRID Maximum %AR (day)

Final %AR (study 

length)

PARENT

Metconazole 5-[(4-Chlorophenyl)methyl]-

2,2-dimethyl-1-(1H- l,2,4-

triazol-1-

ylmethyl)cyclopentanol

CAS No.: 125116-23-6

Formula: C17H22ON3Cl

MW: 319.8 g/mol

SMILES:

CC1(CCC(C1(CN2C=NC=N2

)O)CC3=CC=C(C=C3)Cl)C

 

 cis-Metconazole trans-Metconazole

MAJOR TRANSFORMATION PRODUCTS

M30 2-Hydroxy-3,3-dimethyl-2-

[1,2,4]triazol-1-ylmethylcyclopentyl-(4-chlorophenyl)-

methanone

CAS No.: 153208-73-2

Formula: C17H20O2N3Cl

MW: 333.8 g/mol

SMILES:

CC1(CCC(C1(CN2C=NC=N2

)O)CC3=CC=C(C=C3)Cl)C

Aerobic soil 46808408 13% (368 d) 13% (368 d)

Aerobic aquatic 46902205 7.1% (152 d) 6.5% (182 d)

H3C

H3C

N

N N

HO

Cl H3C

H3C

N

N N

HO

Cl
35

Code Name

(Synonym) Chemical Name Chemical Structure Study Type MRID Maximum %AR (day)

Final %AR (study 

length)

M13 3-(4-chlorobenzyl)-2-hydroxy1-methyl-2-[1,2,4]triazol-1-

ylmethylcyclopentanecarboxylic acid

Formula: C16H18O3N3Cl

MW: 335.8 g/mol

SMILES: 

C(=O)(O)C1C(O)(CN2C=NC

=N2)C(Cc2ccc(Cl)cc2)CC1

Aerobic aquatic 46902205 10.9% (152 d) 10.3% (182 d)

M38

(Hydroxymetconazole)

or

(4-Chlorophenyl) [2-

hydroxy-3,3-dimethyl-2-

1H-1,2,4-triazol-1-

ylmethyl)cyclopentanol]-

methanone

(1RS,5RS,lRS,5SR)-5-(4-

Hydroxybenyl)-2,2-dimethyl-l-

(lH-l,2,4-triazol-1-

lylmethyl)cyclopentanol

Formula: C17H23N3O2

MW: 301.4 g/mol

SMILES: 

c1cc(O)ccc1CC2CCC(C)(C)C

2(O)CN3N=CN=C3

Aqueous 

photolysis

46902202 14.5% (30 d) 14.5% (30 d)

46808405 3.5% (5 d) 2.9% (14 d)

MINOR TRANSFORMATION PRODUCTS

M20 1,2,4-triazole

Formula: C2H3N3

MW: 69.07 g/mol

SMILES: C1=NN=CN1

Aqueous

photolysis 46808405 6.7% (14 d) 6.7% (14 d)

Aerobic soil 46808408 3.92% (235 d) 3.64% (368 d)

M34 1 H- 1,2,4-Triazol- 1 acetic 

acid

Aqueous

photolysis 46808405 7% (14 d) 7% (14 d)
36

Code Name

(Synonym) Chemical Name Chemical Structure Study Type MRID Maximum %AR (day)

Final %AR (study 

length)

M21 (1R,2S,1αS)-α(pChlorophenyl)-2-hydroxy-3,3-

dimethyl-2-(1H-1,2,4-triazol1-ylmethyl) 

cyclopentanemethanol

Aerobic soil 46808408 0.97% (49 d) 0.88% (368 d)

Aerobic aquatic 46902205 7.9% (152 d) 5.4% (182 d)

M11 (5-[(4-Chlorophenyl)-

hydroxy-methyl]-2,2-

dimethyl-l-[l,2,4]triazol-l-ylmethyl-cyclopentanol)

Aerobic soil 46808408 3.53% (151 d) 3.45% (368 d)

Aerobic aquatic 46902205 3.0% (62 d) 2.7% (182 d)

M15 2-Chloro-5-(2-hydroxyl-3.3-

dimethyl-2-[1,2,4]triazol-1-

ylmethyl-cyclopentylmethylphenol Aerobic aquatic 46902205 2.0% (182 d) 2.0% (182 d)

M39 (1RS,5RS,lRS,SSR)-5-Benzyl2,2-dimethyl -1-(lH-l,2,4-

triazol-1-

lylmethyl)cyclopentanol

Aqueous

photolysis

46902202 7.9% (30 d) 7.9% (30 d)

46808405 5.2% (5 d) 2.2% (14 d)
37

APPENDIX B. ECOSAR Output

Table B-1. Comparative Aquatic Toxicity of Metconazole and Major Degradation Products

Compound FW fish 

96-hr 

acute LC50

(mg/L)

FW fish 

chronic 

NOAEC

(mg/L)1

FW 

invertebrate 

48-hr acute 

EC50

(mg/L)

FW 

invertebrate 

chronic 

NOAEC

(mg/L)1

ME fish 

96-hr 

acute 

LC50

(mg/L)

ME fish 

chronic 

NOAEC

(mg/L)1

ME 

invertebrate 

96-hr acute 

LC50

(mg/L)

ME 

invertebrate 

chronic 

NOAEC

(mg/L)1

Nonvascular 

plant 96-hr 

EC50

(mg/L)

Metconazole 1.40

(5.4)

0.012

(0.0029)

2.2

(5.9)

0.092

(0.031)

3.4

(6.3)

0.070

(0.011)

0.36

(0.78)

0.062

(≥0.059)

0.73

(0.20)

2

M30 14.92 0.116 25.2 0.763 - - - - 4.55

M38 

(Hydroxymetconazole) 8.05 0.053 3.9 0.430 2.9 0.135 3.09 2.24 2.83

M13 360.543 1.284 111.9 10.710 1048.43 2.146 104.62 156.3003 64.23 1 ECOSAR estimated chronic value is defined as the geometric mean of the no observed effect concentration (NOEC) and the lowest observed 

effect concentration (LOEC).

2 Green algae

3 Endpoint exceeds predicted water solubility of compound.

BOLD values are ECOSAR (v1.00) toxicity estimates (lowest toxicity value if multiple ECOSAR classes are available, i.e., the most 

toxic).

Italic values are from submitted toxicity studies (most sensitive endpoint if multiple are available) 

FW = freshwater and ME = marine/estuarine
38

APPENDIX C. SIP v.1.0 Inputs and Outputs

Table C-1. Inputs

Parameter Value

Chemical name Metconazole

Solubility (in water at 25oC; mg/L) 30.41

Mammalian LD50 (mg/kg-bw) 595

Mammalian test species laboratory rat

Mammalian NOAEL (mg/kg-bw) 7.52

Mammalian test species laboratory rat

Avian LD50 (mg/kg-bw) 777

Avian test species northern bobwhite quail

Mineau scaling factor 1.15

Mallard NOAEC (mg/kg-diet) 120

Bobwhite quail NOAEC (mg/kg-diet) 58 1 Based on product chemistry. Solubility is lower (18.7 mg/l) for the cis isomer which is the dominant 

constituent (ca. 85%) of metconazole TGAI. Conclusions do not change using the lower solubility. 2 Calculated in T-Rex based on NOAEL = 150 mg ai/kg bw.

Table C-2. Mammalian Results

Parameter Acute Chronic

Upper bound exposure (mg/kg-bw) 5.2288 5.2288

Adjusted toxicity value (mg/kg-bw) 457.6505 5.7687

Ratio of exposure to toxicity 0.0114 0.9064

Conclusion*

Drinking water 

exposure alone is NOT a 

potential concern for 

mammals

Drinking water exposure 

alone is NOT a potential 

concern for mammals

Table C-3. Avian Results

Parameter Acute Chronic

Upper bound exposure (mg/kg-bw) 24.6240 24.6240

Adjusted toxicity value (mg/kg-bw) 559.7737 5.9535

Ratio of exposure to acute toxicity 0.0440 4.1360

Conclusion*

Drinking water 

exposure alone is NOT 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.
39

APPENDIX D. STIR v.1.0 Inputs and Outputs

Table D-1. Input

Application and Chemical Information

Enter Chemical Name Metconazole

Enter Chemical Use turf

Is the Application a Spray? (enter y or n) y

If Spray What Type (enter ground or air) ground

Enter Chemical Molecular Weight (g/mole) 319.8

Enter Chemical Vapor Pressure (mmHg) 1.58E-101

Enter Application Rate (lb ai/acre) 0.6

Toxicity Properties

Bird

Enter Lowest Bird Oral LD50 (mg/kg bw) 777

Enter Mineau Scaling Factor 1.15

Enter Tested Bird Weight (kg) 0.178

Mammal

Enter Lowest Rat Oral LD50 (mg/kg bw) 595

Enter Lowest Rat Inhalation LC50 (mg/L) >5.5882

Duration of Rat Inhalation Study (hrs) 4

Enter Rat Weight (kg) 0.35 1 Based on product chemistry. Vapor pressure is 7.8x10-8 torr for the cis isomer which is the dominant constituent 

 (ca. 85%) of metconazole TGAI. Conclusions do not change using cis isomer vapor pressure. 2 MRID 46808433

 Table D-2. Output

Results Avian (0.020 kg )

Maximum Vapor Concentration in Air at Saturation (mg/m3) 2.72E-06

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 3.42E-07

Adjusted Inhalation LD50 4.07E+01

Ratio of Vapor Dose to Adjusted Inhalation LD50 8.40E-09

Exposure not Likely 

Significant

Maximum Post-treatment Spray Inhalation Dose (mg/kg) 6.34E-02

Ratio of Droplet Inhalation Dose to Adjusted Inhalation LD50 1.56E-03

Exposure not Likely 

Significant

Results Mammalian (0.015 kg )

Maximum Vapor Concentration in Air at Saturation (mg/m3) 2.72E-06

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 4.30E-07

Adjusted Inhalation LD50 3.33E+02

Ratio of Vapor Dose to Adjusted Inhalation LD50 1.29E-09

Exposure not Likely 

Significant

Maximum Post-treatment Spray Inhalation Dose (mg/kg) 7.97E-02

Ratio of Droplet Inhalation Dose to Adjusted Inhalation LD50 2.40E-04

Exposure not Likely 

Significant