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

., Ecologist t: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 Risk Branch I

### ~ Environmental Fate and Effects 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 unce rtainty 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 amp hipod)

– (metconazole; TGAI)

o EFED recommends that the registrant consider Agency

- wide guidelines for chronic testing of freshwater and estuarine/marine organisms 1

, 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 freshwat er 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 (metconaz ole; TGAI)

• Non

- guideline ( Tier II ): R esidue in pollen and nectar (recommendation pending risk identified in Tier I studies) (TEP)

• Non

- guideline ( Tier II ): S emi

- field testing for pollinators (tunnel and feeding studies) (recommendation pending risk identifi ed in Tier I studies) (TEP)

• 850.3040 ( Tier III ): F ull

- 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 analy tical 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 pro vided in terms of lb ai/volume. EFED requests that the registrant review all labels to ensure that rates are also p resented 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 

# P roblem 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 

## C H 3 

## C

H 3 

## N N N

O H

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 Wa ter 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
AP PENDIX 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 o f the implementation of the Registration Review program 3 

### 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 U nited S tates in 2007 as a systemic fungicide . I t is currently registered for use on a variety of food crops and turf. P revious Section 3
assessments for metconazole typically identified risk concerns for birds (acute and chronic),
mammal s (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 us e 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 expos ure, 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 invertebrate s )

.

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

- reevaluation/registrati on

- 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

repo rted 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, 20 11 ). The i ntersection s of the blue line (daily EEC)
and horizontal line s (toxicity value s ) represent the projected time when the risk quotient ( RQ ) is equal to the Agency’s level s of concer n ( 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

, 2014 b )

. 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 conce ntration 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 1990Daily EEC (μg/L)

0 25 50 75 100 125

Vascular plant NOAEC 0.51 μ g a.i./L Fresh Water fishNOAEC:2.9 μ g a.i./L Estuarine/Marine invertebrate NOAEC: 11 μ g a.i./L Vascular plant EC 50 : 22 μ g a.i./L Fresh water invertebrate NOAEC: 31 μ g 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 plan t.

3.2. Overview of Pesticide Use and Usage

Metconazole u ses and application rates are summarized in Table 1

. This i nformation was obtained from the most recent Label Use Information System ( LUIS ) report provided by the Biological and Economic Analysis Div ision (BEAD) (USEPA

, 2015 a )

. 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 number s 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.

S ome 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
list 5 

### )

. Although EFED will make assumpt ions in the absence of application interval restriction s, 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 ( d ays) Season /Crop or [ Annual ]
Maximum Application Rate (lb ai/A) Bushberry ( subgroup 13

- 07B) Ground and aerial spray;

c hemigation 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 ( d ays) 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 0.00002268 2 NS NS NS

Canola \ Rape Seed treatment 0 .00001432 2 NS NS NS

Canola (unspecified) Ground and aerial spray; chemigation 0.125 1 NA 0.125

Seed treatment 0.0000263 2 NS NS NS

Corn Ground and
aerial broadcast; chemigation; direct spray;
banded 0.0821 4 or NS 7 0.3519

Seed treatment 0.00015 2 NS NS NS

Cotton Ground and
aerial broadcast; chemigation; direct spray;
banded 0.0821 3 7 0.2463

Seed treatment 0.000105 2 NS NS NS

Golf c ourse t urf Spot t reatment 0.0063 3 2 14 [ 2 ]

Ground s pray 0.6 2 14 [2]

Oats Ground and
aerial broadcast; chemigation; direct spray;
banded 0.0997 2 6 0.1994

Seed treatment 0.00002268 2 NS NS NS

Ornamental (sod farm) Spot treatment 0.0063 3 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 0.125 5 NS 14 [2] Ground spray 0.272 NS 14 [2]

Drench 0.000312457 6 NS 14 [2]

Peanuts Ground and

a erial s pray ;

c hemigation 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 ( d ays) Season /Crop or [ Annual ]
Maximum Application Rate (lb ai/A)

Pistachio Ground and aerial spray; chemigation 0.125 4 14 0.5

Residential l awns 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 f ruit 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 0.000305 2 NS NS NS

Sugarcane Ground and
aerial broadcast; chemigation; direct spray;
banded 0.0815 4 NS 0.3262

Tree n uts 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 0.0000263 2 NS NS NS

### 10 Use Method of Application Maximum Single Application Rate (lb ai/A) 1 Maximum
Number of Applications Minimum Application Interval ( d ays) 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 0.00002 2 6 8 2 NS NS NS

NS

– Not Specified

N A

– 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/ft 2



### 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 temperature s . 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 partit ion rapidly to the sediment ( DT 50 

### in water rang ing from 1

- 1 9 days ) and shown to sl owly degrade in sediment ( DT 50 

### for the total system rang ing from 140

- 990 days (MRID 46902205) )

. Based on three aerobic soil metabolism studies, the half

- life values are in t he 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 metcona zole dissipated with a DT 50 

### 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 K oc values ranging from 1026 to 2723 ml/g. This K oc 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. B ioaccumulation 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) indicate d a fairly low bioconcentration in bluegill sun fish

. D epuration was rapid with DT 50 

### 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 Product s
Parameter Value Source Comment

Metconazole

Chemical Name 5

- [(4

- Chlorophenyl)methyl]

- 2,2

- dimethyl

- 1

- (1H

l,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 C 17 H 22 ON 3 Cl MRID 46808404

Molecular Weight 319.8 MRID 46808404

Log Kow 3.85 MRID 46808404 Flask shaking method

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

Vapor Pressure (25 o C) 1.58 ×10

- 10 mm Hg Product Chemistry

pKa 11.38 Product Chemistry

Henry’s Law constant 3.03 ×10

- 10 atm m 3 mol

- 1 EPI Suite (v4.11)

Hydrolysis t 1/2 = 0

(stable) MRID 46808404 Stable at 120 hours

(pH 5, 7, 9) 

### C H 3 

### C

H 3 

### N N N

O H

Cl

C H 3 

### C

H 3 

### N N N

O H

Cl

### 12 Parameter Value Source Comment

Aqueous Photolysis t 1/2 = 72 days

t 1/2 = 90 days MRID 46902202
MRID 46808405 MRID 46902202 M38 (Hydroxy metconazole)

– 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 t 1/2 = 140 days

t 1/2 = 50 days MRID 46808406
MRID 46902203

Aerobic Soil Metabolism t 1/2 = 630 days sandy loam

t 1/2 = 257 days clay soil

t 1/2 = 267 days sandy loam

t 1/2 = 193 days silty clay

t 1/2 = 204 days sandy loam

t 1/2 = 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 DT 50 > 120 days

DT 50 > 360 days

(Stable) MRID 46808409
MRID 46808410

Aerobic Aquatic
Metabolism t 1/2 = 990 days

(Stable) MRID 46902205 M13

– 10.9 %
M11

– 3 %
M15

– 2.0%
M21

– 8.0%
M30

– 7.1%
Organic Carbon Partition Coefficient (K OC ) mL/g 2723, 1115, 1026

, 1312 MRID 46808411

Fish B ioconcentration BCF values: 63

- 68 (fillet)

, 182

- 218 (viscera), 124

- 128 ( whole fish )
Depuration DT 50 = 1

- 5

– 1.7 days MRID 46808425

Terrestrial Field Dissipation t 1/2 = 120 days

t 1/2 = 60 days

t 1/2 = 187 days

t 1/2 = 94 days

t 1/2 = 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

- 1H

1,2,4

- 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 C 17 H 20 O 2 N 3 Cl EPI Suite (v4.11)

Molecular Weight 333.8 EPI Suite (v4.11)

Log Kow 2.84 EPI Suite (v4.11)

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

Vapor Pressure (25 o 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 m 3 mol

- 1 EPI Suite (v4.11)

M13

Chemical Name (1 S,2R,3R)

- 3

- (p

- Ch1orobenzyl)

- 2

- hydroxy

- 3

- methy1

- 2

- (1 H

- 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 C 16 H 18 O 3 N 3 Cl EPI Suite (v4.11)

Molecular Weight 335.8

Log Kow 2.50

Aqueous Solubility (25 o C) 136.3 mg/L

Vapor Pressure (25 o C) 9.8 ×10

- 12 mm Hg

Koc 151.4

Henry’s Law constant 1.28 ×10

- 15 atm m 3 mol

- 1

Hydroxymetconazole (M38)

Chemical Name (4

- Chlorophenyl) [2

- hydroxy

- 3,3

- dimethyl

- 2

- 1H

1,2,4

- 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 C 17 H 23 N 3 O 2 EPI Suite (v4.11)

Molecular Weight 301.4

Log Kow 3.07

Aqueous Solubility (25 o C) 109.6 mg/L

Vapor Pressure (25 o C) 5.47 ×10

- 10 mm Hg EPI Suite (v4.11)

Koc 2543

Henry’s Law constant 4.26 ×10

- 14 atm m 3 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 CO 2 

### 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 4690220 2).

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 E nvironmental 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/attai ns_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

mo re 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. Toxico logical 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.

A cute and ch ronic 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)
database 10 

### , which employs a literature search engine for lo cating 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 examin ed residues in pollen and nectar following product application. Ecological Structure Activity Relationship (ECOSAR) methods 11 

### of the major degradate s ’ (M30, M13, and hydroxymetconazole) toxicity are discu ssed 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 Animal s

Study Type Species Toxicity Value MRID

Acute

– Freshwater Fish Rainbow trout ( Oncorhynchus mykiss ) 28

- day LC 50 = 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

- a ssessing

- pesticide

- risks/aquatic

- life

- benchmarks

- pesticide

registration/

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 LC 50 = 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 LC 50 = 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 EC 50 = 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 LC 50 = 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 EC 50 = 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 EC 50 = 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 EC 50 = 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 EC 50 = 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 EC 50 = 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 EC 50 = 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 EC 50 > 16 4

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 EC 50 ) is reported.

4 mg total ai/L because of uncertainty about exposure concentrations.



### Toxicity d ata are not available for the major degradation product s (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, i t 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, t he ECO SAR 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 formulatio n for difenoconazole ( see USEPA, 2015 b ) 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 Organi sms

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 ) LD 50 = 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 LC 50 = 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 ) LC 50 >5230 mg ai/kg diet
NOAEC = 1370 mg a i/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 s ignificant reduction in ratio of eggs not cracked/eggs laid 46808417

Acute

– Mammalian
Oral Dose Laboratory rat (Rattus norvegicus) LD 50 = 595 mg ai/kg bw (female) 5,6 44721512

Chronic

– Mammalian

Two
Generation Reproduction NOAEC = 150 mg ai/kg diet 7,8

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 F 2 offspring) effects 46808447

Acute

– Terrestrial
Invertebrate
Contact Earthworm ( Eisenia foetida ) LC 50 > 952 mg ai/kg substrate 9

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

L C 50 = 88 (61

- 130) 2 μg ai/bee

NOAEC = 11 μg ai/bee
LOAEC = 24 μg ai/bee based on mortality

Acute Contact Toxicity

LD 50 > 95.3 μg ai/bee

NOAE L ≥ 95.3 μg ai/bee
LOAE L > 95.3 μg 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

L C 50 = 76.6 μg formulation/bee

L C 50 = 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

LD 50 > 532.5 μg formulation/bee

LD 50 > 26.8 μg metconazole/bee

NOAE L = 6.69 μg metconazole/bee
LOAE L = 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 0 1 F (12.5 % pyraclostrobin; 7.32 % metconazole)

Acute Oral Toxicity
LC 50 = 21.5 μg formulation/bee

L C 50 = 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
effect s w ere 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 LD 50 = 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 we ight loss (male and female), and clinical signs of toxicity (male and female)

. 5 Based on an 85:15 ratio mixture of c is:trans isomers

. 6 The LD 50 = 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 (m ale) 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

EC 25 > 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

EC 25 = 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

EC 25 > 0.097/0.098 2

NOAEC ≥ 0.097/0.098
LOAEC > 0.097/0.098 based on no
effects (all test species)

Dicot

EC 25 > 0.097/0.098 2 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

EC 25 > 0.60

NOAEC ≥ 0.60
LOAEC > 0.60 based on no effects (all test species)

Dicot

EC 25 = 0.44 (0.11

- 1.8) 1 based on
radish reduced shoot dry weight

EC 05 = 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

EC 25 > 0.097/0.10 2

NOAEC ≥ 0.097/0.10
LOAEC > 0.097/0.10 based on no effects (all test species)

Dicot

EC 25 > 0.097/0.10 2 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

- ecologic al

- risk

assessment

- 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 i n one incide nt 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 insec ticide (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 Pathw ays of Concern

The use patterns and environmental fate properties of metconazole indicate that exposure to non

target aquatic and terrestrial organisms may occur from direct spray and off site movement via

spray drift and runoff

.

An additional exposure pat hway 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 bioaccumulat e 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 a lone
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 pot ential 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, th e value is from a single study conducted under specific
conditions and is close to the lower end criteri on of log Kow = 4. Furthermore, metconazole is expected to be persistent and accumulate in the environment; therefore, residues in fish may increase ov er time, especially in static systems, to the extent that bioaccumulation occurs.

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

- science

- and

- assessing

- pesticide

- risks/models

- p esticide

- 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
cha racterized and integrated to assess risk. This will be accomplished using a n 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 r isk 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 me tconazole 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 op en 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 stud y ( 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). H ydroxymetconazole is likely equal in toxicity to
metconazole and was a major aque ous 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 as sessment, 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. I nclusion of the se 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 i n the metconazole DWA, consi stent 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 re

application 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 C alculator (PWC) ). 19 

### Bioaccumulation potential in aquatic organisms will be estimated to assess exposure to piscivorus animals ( e.g. , Kow (based) Aquatic BioAccumulation Model (KABAM)) 1 9 

### given that the available fate data of metconazole (log

Kow = 3.85) sug gests 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 c ontaminated fish ), direct applic ation, 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 DT 50 

### 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 terres trial and semi

aquatic pla nts.

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 i ndirect effects to biological receptors (USEPA, 2004). As discussed previously, data will be obtained from registrant

submitted studies and from literature studies identified in ECOTOX.

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

- science

- and

- assessing

- pesticide

- risks/m odels

- p esticide

- 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 furthe r 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 de veloped 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 20 

### outlines recommendations on specific scientific and technical issue s 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 specif ic 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 ris ks 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 differen ces 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 Nationa l 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, t his 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 registr ation 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. T his 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

- assessments

based

- nas

- report

### 26 agencies have fully developed and imp lemented 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. Endoc rine 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 in cluded 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 recommend ed by the ROCKS committee (USEPA

, 2008)

. C oncentrations in surface and ground water will be estimated using current guidance and models. 23 

### Additionally, EFED may update the previously conducted ag gregate 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 d ata gaps for metconazole are defined in Sections 6.8.1 and
6.8.2 , respectively. Studies are i dentified 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 e nvironmental fate data for metconazole are adequate for conducting a risk assessment; however, an ECM/ILV is needed for monitoring me tconazole residue s in water ( Table 8 )

. EFED does not recommen d 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 )

T able 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

- a ssessment

### 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/A quatic
metabolism 46808409 Supplemental No

- 46808410 Acceptable

835.1230
835.1240 Adsorption / desorption and leaching 46808411 Supplemental No

-

835.6100 Terrestrial f ield d issipation 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

D ata gaps for metconazole remain ( Tables 9
, 10
, 11, and 1 2 ) ; 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, fres hwater 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 organisms 24

, 25 

### because the 850 guidelines are in the process of bein g 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 s ubchronic 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 ): S emi

- field testing for pollinators (tunnel and feeding studies) (recommendation pending risks identified in Tier I studies) (TEP)

• 850.3040 ( Tier III ): F ull

- 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 metcona zole are of s imilar toxicity and that M13 may be less toxic. EFED is not aware of any evidence that the se degradates may be more toxic than metconazole . A previous assessment concluded that risk conclusions would not change if M30 were included in the ex posure 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 residue s to accumulat e 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 Marin e 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 inv ertebrates (freshwater and marine

estuarine 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 sub chronic 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
sub chronic testing . The test concentrations should be relevant to those s howing effects in the
available subchronic tests ( i.e., testing should include concentration s 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 organisms 27

, 28 

### because the 850 guidelines are in the process of being finalized. A protocol must be submitted for review prior to initiating the stud ies

.

Chronic t oxicity data from other sources will be u sed 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 Gaps A

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. Meth ods 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

- ass ociated 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 Yes 1 4 Study endpoints are under re

review. A new study is not
recommended.

5 There is some uncertainty about the bioavailable exposure concentration. A new study i s 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 Yes 2,3

850.1740 Whole sediment acute toxicity, marine

invertebrates - - No

- Whole sediment chronic toxicity,
freshwater
invertebrates - - Yes 3

- Whole sediment chronic toxicity,
marine

- estuarine

invertebrates - - Yes 3

850.5400 B Aquatic plant growth (freshwater green alga) 46808429 Supplemental 4 Yes 4

Aquatic plant growth (freshwater diatom) 46808431 Supplemental 4 Yes 4

Aquatic plant growth

(saltwater diatom) 46808432 Supplemental 4 Yes 4

850.5400 B Aquatic plant growth (Cyanobacteria) 47795007 Supplemental Yes 5

850.4400 B 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 marin e/estuarine invertebrates (MRID 46808423), toxicity to freshwater algae (MRID 46808418) , and cyanobacteria (MRID 46808430) ] but were subsequently replaced with valid studies.

B As of July 2012 the new guideline numbers are 850.4500 (Algal toxicity) and 850.4550 (Cyanobacteria toxicity)
BOLD = Recommended Studies

### 31 Table 1 0 . 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 o n

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 recomm ended 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

Non

guideline Adult honeybee chronic oral toxicity (Tier 1) - - Yes 1,2

Non

guideline Larval honeybee acute
and chronic oral toxicity (Tier 1) - - Yes 1, 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

Non

guideline Semi

- field testing for pollinators (tunnel and feeding studies) ( Tier II) - - Yes 1 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 II I ) - - Yes 1

Non

guideline Residues in Pollen and Nectar (Tier II honeybee testing) 49459604
49459605 Supplemental Supplemental Yes 1 ,2

BOLD = Recommended Studies

### 32 Table 1 2 . Ecological Effects Data Requirements (TEP) for Plants Exposed to Metconazole and Data Gaps

Guideline Description MRID Classification Data Gap? Comments

850.4100 A Terrestrial plant toxicity (Tier I or Tier II seedling emergence) 46805103
46902214 Acceptable Acceptable No

850.4150 B 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
C ontamination. 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 Agricul tural 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

T oxic 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 P rograms, 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 Ston e 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. 2014 b. 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. 2015 a

. Metcona zole (125619) Label Reports Package in Support of Registration
Review. Office of Pesticide Programs, Biological and Economic Analysis Division. March 31, 2015

.

USEPA. 2015 b

. 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: C 17 H 22 ON 3 Cl
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

- ylmethyl

cyclopentyl

- (4

- chlorophenyl)

- methanone

CAS No .: 153208

- 73

- 2
Formula: C 17 H 20 O 2 N 3 Cl
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) 

### C H 3 

### C

H 3 

### N N N

O H

Cl C H 3 

### C

H 3 

### N N N

O H

Cl

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

M13 3

- (4

- chlorobenzyl)

- 2

- hy droxy

1

- methyl

- 2

- [1,2,4]triazol

- 1

- ylmethyl

cyclopentanecarboxylic acid

Formula: C 16 H 18 O 3 N 3 Cl
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: C 17 H 23 N 3 O 2 MW: 301.4 g/mol
SMILES: c1cc(O)ccc1CC2CCC(C)(C)C 2(O)CN3N=CN=C3 Aq ueous photolysis 46902202 14.5% (30 d) 14.5% (30 d)

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

MINOR TRANSFORMATION PRODUCTS

M 20 1,2,4

- triazole

Formula: C 2 H 3 N 3 MW: 69.07 g/mol
SMILES: C1=NN=CN1 Aq ueous 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

Aq ueous 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(p

Chlorophenyl)

- 2

- hydroxy

- 3,3

- dimethyl

- 2

- (1H

- 1,2,4

- triazol

1

- 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

- yl

methyl

- 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

- cyclopentylmethyl

phenol Aerobic aquatic 46902205 2.0 % ( 182 d) 2.0 % ( 182 d)

M39 (1RS,5RS,lRS,SSR)

- 5

- Benzyl

2,2

- dimethyl

- 1

- (lH

- l,2,4

- triazol

- 1

- lylmethyl) cyclopentanol Aq ueous 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 LC 50

(mg/L) FW fish
chronic
NOAEC (mg/L) 1 FW
invertebrate
48

- hr acute
EC 50 (mg/L) FW
invertebrate
chronic
NOAEC (mg/L) 1 ME fish
96

- hr

acute
LC 50 (mg/L) ME fish
chronic
NOAEC (mg/L) 1 ME
invertebrate
96

- hr acute
LC 50 (mg/L) ME
invertebrate
chronic
NOAEC (mg/L) 1 Non

vascular plant 96

- hr
EC 50 (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 360.54 3 1.284 111.9 10.710 1048.4 3 2.146 104.62 156.300 3 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 EC OSAR (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/e stuarine

### 38 

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

Table C

- 1. Inputs

Parameter Value

Chemical name Metconazole Solubility (in water at 25 o C; mg/L) 30.4 1

Mammalian LD 50 (mg/kg

- bw) 595 Mammalian test species laboratory rat

Mammalian NOAEL (mg/kg

- bw) 7.5 2 Mammalian test species laboratory rat

Avian LD 50 (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 i n 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

- 10 1

Enter Application Rate (lb ai/acre) 0.6

Toxicity Properties

Bird

Enter Lowest Bird Oral LD 50 (mg/kg bw) 777 Enter Mineau Scaling Factor 1.15 Enter Tested Bird Weight (kg) 0.178

Mammal

Enter Lowest Rat Oral LD 50 (mg/kg bw) 595

Enter Lowest Rat Inhalation LC 50 (mg/L) >5.588 2
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/m 3 ) 2.72E

- 06

Maximum 1

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

- 07

Adjusted Inhalation LD 50 4.07E+01

Ratio of Vapor Dose to Adjusted Inhalation LD 50 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 LD 50 1.56E

- 03 Exposure not Likely Significant

Results Mammalian (0.015 kg )
Maximum Vapor Concentration in Air at Saturation (mg/m 3 ) 2.72E

- 06

Maximum 1

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

- 07

Adjusted Inhalation LD 50 3.33E+02

Ratio of Vapor Dose to Adjusted Inhalation LD 50 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 LD 50 2.40E

- 04 Exposure not Likely Significant