### 2



## 1. Executive S ummary The Environmental Fate and Effects Division (EFED) has completed the problem formulation for the ecological risk, environmental fate, endangered species, and drinking water assessments to be conducted as part of the registration review of tetraconazole (PC Code 120603 ) . The problem formulation describes the methods planned to be used during the completion of the drinking water and ecological risk assessments in support of registration review and provides an ove rview of the environmental fate, ecological eff ects , and potential risks associated with the use of tetraconazole as well as uncertainties unique to the risk assessment . This document also identifies additional studies using either technical grade active ingredient (TGAI) or typical end

- use product (TEP) that would be beneficial for conduct ing an ecological risk assessment of tetraconazole

. Risk findings from previously conducted risk assessments are summarized in the following table :

Table 1 .1. Summary of Risk Concerns and Issues Identified for Tet raconazole in Previous Assessments

Birds Mammals Terr.

Plants Terr.

Inverts Fish BCF Aquatic Inverts Aquatic

Plants Persistence Degradates of Concern
Yes 1 Yes 2 Yes 3 No No No No Yes 4 Yes NA 5
“Yes” = Risk concerns or issues were identified or presumed in previous assessments

1 Acute and chronic risk

2 Chronic risk

3 LOC for terrestrial and semi

- aquatic monocots and dicots is exceeded for application to turf for seedling emergence

4 Risk cannot be precluded due to lack of data (for non

- vascular plants only)

5 NA = Not Assessed



### The following environmental fate data gaps were identified for the parent tetraconazole :

 835.4200: Anaerob ic s oil m etabolism: 4 soil systems

 835.4400: Anaerobic a quatic m etabolism: 1 additional sedime nt

- water system

 860.1380: Storage s tability in soil and water

 850.7100: ECM/ILV: Environmental c hemistry m ethods and i ndependent l aboratory v alidation in s oil and water (Parent only)

The following ecotoxicity data gaps were i dentified for the parent tetraconazole (see Section 11b for details):

 850.1 350 : Saltwater invertebrate life cycle (TGAI)

 850.140 0 : Saltwater fish early

- life stage (TGAI)

 850.1500: Fresh water fish life cycle (TGAI)

 Non

- guideline : Whole sediment invertebr ate chronic toxicity

– two freshwater amphipod Hyalella azteca and Chironomus tentans and one estuarine/marine amphipod Leptocheirus plumulosus ) (TGAI)

 Guideline 850.4500 : Freshwater green alga , freshwater and marine diatom (TGAI)

 Guideline 850.4550 : Cyanobacteria toxicity (TGAI)

 Guideline 850.2100 : Avian oral toxicity for passerine (TGAI)

 Non

- guideline : H oneybee adult chronic oral toxicity (TGAI)

 Non

- guideline : H oneybee larval acute and chronic oral toxicity (TGAI)

 Non

- Guideline: Residue in poll en and nectar (recommendation pending risks identified in Tier I studies) (TEP)

 Non

- Guideline: Semi

- field testing for pollinators (tunnel and feeding studies)

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

 Guideline 850.3040: Full

- field testing for pollinators (recommendation pending risk identified in Tier II studies) (TEP)

 Guideline 850.4100: Seedling Emergence and Seedling Growth

 Guideline 850.4150: Vegetative Vigor

For a non

- guideline study, a protocol should be submitted in advanc e of conducting the study.

Uncertainties : Tetraconazole is a chiral compound; however, only the racemic mixture was used in toxicity testing. The risk assessment does not take into account the difference in the mode of action of the enantiomers of tetraco nazole or their differences in fate or toxicity in the environment.

Many of the labels for agricultural use s did not provide information on the maximum number of applications allowed per year, the maximum annual rate (in terms of lbs ai/A), or the minimum

re

- application interval.

 Registrations 66330

- 422 for corn and soybeans and 7969

- 361 for soybeans do not provide any application rate information. The maximum single application rate, and the maximum, application rate per year including the number of applications and reapplication intervals are needed for the risk assessment.

 Registration 60063

- 12 for peanuts, pecan and sugar beets does not list maximum application rate per year. The number of applications and the maximum application rate should b e rep orted on an annual basis.

 Seasonal, rather than yearly application information is provided for two uses on registration numbers 80289

- 18 for peanuts, pecan and soybeans and 80289

- 8 for 13

- 07F small fruit vine climbing subgroup, except fuzzy kiwifruit and 13

- 07G low growing berry

su bgroup. The number of applications and the maximum application rate should be reported on an annual basis.

If the labels are not clarified, conservative a ssumptions , such as: multiple seasons or crop cycles may be assumed for some crops when performing t he risk assessment, will be made for these uses as outlined in Appendix I

.



## 2. Introduction

Tetraconazole (±1

- [2

- (2,4

- dichlorophenyl)

- 3

- (1,1,2,2

- tetrafluoroethoxy)

- propyl]

- 1H

- [1,2,4]tri

azole, CAS 112281

- 77

- 3) was first registered in August,1993 as a broad s pectrum systemic fungicide with protective, curative, and eradicat iv e properties. Tetraconazole is a chiral compound and a triazole systemic fungicide, which acts primarily by interfering with cell growth, particularly the ability to build cell walls, thro ugh inhibition of ergosterol biosynthesis in cell membranes.

EFED evaluated the most recent ecological risk assessments for tetraconazole in association with the update d toxicity, exposure, and usage information to determine if sufficient data are avail able and if further updates are needed to support registration review.

### 4



## 3. Use Characterization
The current registered uses in agricultural crops including, sugar beets, soybeans, pecans, peanuts, grapes and corn. T etraconazole is formulated as emulsifiable concentrate for broadcast application by ground and aerial methods, as well as the ch e migation. Single application rates vary from 0.04 lbs a.i./A (low growing berry subgroup) to 0.13 lbs a.i./A (pecan) and the annual maximum rate is 0.523 lbs a.i./A acco rding to an analysis by the Biological and Economics Analysis Division (BEAD) (USEPA 2014a). Table 2. 1 is a summary of the maximum rates for registered uses of tetraconazole

.

Table 2.1 Maximum Application Rates for Registered Uses of Tetraconazole

Use S ite Single Maximum Application Rate (lb a.i./A) Maximum

Number of Applications Minimum

Application Interval (days) Maximum

Application Rate Per Crop Cycle (or Year ) (lb a.i./A )
13

- 07F. Small fruit vine climbing subgroup, except fuzzy kiwifruit 0.04 08 NS 1 ,2 14 0.08 17

13

- 07G. Low growing berry subgroup 0.04 08 4 14 0.16 33

Corn (field ) 0.09 03 1 NS 2 ( 0.09 03 ) 3

Corn (pop) 0.0894 NS 2 7 ( 0.0 897 ) 3
Peanuts (unspecified) 0.1061 NS 4,2 14 0.4246

Pecan 0.1306 NS 4,2 14 0.5226
Soybeans (unspecified) 0.0753 NS 1 ,2 15 ( 0.1509 ) 3
Sugar beet 0.102 1 2 21 0.2042

1 NS

– Not Specified , two applications are assumed based on the maximum rate per crop cycle.

2 NS

– Not specified, registrant input is required

3 The number in bold represents the maximum annual application rate

4 NS

- Not specified, 4 applications are assumed based on the maximum rate per crop cycle.



### According to BEAD Screen Level Usage Analysis (SLUA) , application to sugar beets at an average rate of 40,000 lbs per year is the highest use followed by soyb eans at 30,000 lbs per year on average (USEPA 2014a). Table 2. 2 shows the average agricultural annual us es (2004

- 2012).

Table 2. 2 . Tetraconazole SLUA (2004

- 2012) 1

Crop Average lbs. (a.i.) Percent Crop Treated

Average Maximum

1 Corn <500 <1 <2.5

2 Grapes 1,000 5 10

3 Peanuts <500 <1 <2.5

4 Soybeans 30,000 <2.5 <2.5

5 Sugar Beets 40,000 30 50

1 Screen Level Usage Analysis (SLUA) data sources include: USDA

- NASS (United States Department of Agriculture's National Agricultural Statistics Service) (2004

- 2012) Private Pesticide Market Research (pesticide usage data from 2004 to 2012)

### 5

California Department of Pesticide Regulation (DPR) Pesticide Use Reporti ng (PUR) data for 2004 to 2011 Additional registered uses may exist but are not included because the available surveys do not report usage (e.g., small acreage crops).



### EFED will use application scenarios that result in maximum exposure scenarios for a giv en use for the risk assessment

. Failure of the label to specify the maximum single application rate, the application interval , the annual maximum rate (lb ai/A/year), and application method may result in conservative assumptions.

For tetraconazole

, several label issues were identified

. Appendix I has more details on missing information and a conservative assumptions may be made based on missing information

.

 Registrations 66330

- 422 for corn and soybeans and 7969

- 361 for soybeans do not provide

any app lication rate information. The maximum single application rate, and the maximum application rate per year including the number of applications and reapplication intervals are needed for the risk assessment.

 Registration 60063

- 12 for peanuts, pecan and sug ar beets does not list maximum application rate per crop cycle or per year. The number of applications and the maximum application rate should be reported on an annual basis. In the absence of yearly information, multiple seasons or crop cycles may be assu med for some crops when performing the risk assessment.

 Seasonal, rather than yearly application information is provided for two uses on registration numbers 80289

- 18 for peanu ts, pecan and soybeans and 80289

- 8 for 13

- 07F small fruit vine climbing subgrou p, except fuzzy kiwifruit and 13

- 07G low growing berry subgroup

. The number of applications and the maximum application rate should b e reported on an annual basis. In the absence of yearly information, multiple seasons or crop cycle s may be assumed for som e crops when performing the risk assessment , based on input from the BEAD

.



## 4. Conclusions from Previous Risk Assessments

a. Ecological Risk Assessment The Agency has previously conducted several ecological risk assessments on tetraconazole including for new uses on sugar bee t ( USEPA 2004 a , DP 30 2 899 and USEPA 2005, DP 313005 ) ; soybeans

, peanuts

, sugar beets

, pecans, and turf (USEPA 2006 a , D331424+); grapes (USEPA 2008 a , D350213+ ) ; small fruit vine climbing subgroup 13

- 07F (except fuzzy kiwifruit), low growing berry subgroup 13

- 07G, and corn (USEPA 2010 a , D381443+) . Tetraconazole is very persistent and has potential to accumulate in soil and water. P revious risk assessment demonstra ted that the tetraconazole concentration continuously accumulates in pond water over the 30 years of the PRZM/EXAM simulation ( USEPA 2010a, D381443+ ). This accumulation is true for all modeled scenarios. T he most recent assessment conducted on sugar beet s (USEPA 2014b, D 416108+ ) incorporate d a pollinator risk assessment framework for terrestrial exposures (USEPA 201 4c ) and a modification of the default spray drift numbers for the aquatic modeling (6.2% and 12.5% for ground and air applications respectively ) (USEPA 201 4b)

.

In the most recent risk assessment, no direct risk concerns were identified for:

 Freshwater fish (acute and chronic)

### 6

 Estuarine/marine fish (acute and chronic)

 Freshwater invertebrates (acute and chronic)

 Estuarine/marine invertebrates (acu te and chronic)

 Aquatic vascular plants

 Benthic invertebrates (acute and chronic)

 Honeybees (acute and dietary)

 Mammals (acute)

Direct risk concerns were identified for the following groups:

 Birds, reptiles, and land

- phase amphibians (acute and chronic)

 Mammals (chronic for both dose

- based and dietary

- based scenarios)

 Aquatic non

- vascular plants (presumed)



## b. Drinking Water Exposure Assessment s

Only the parent tetraconazole was considered as the stressor of concern for drinking water

exposure based on the MARC memorandum of the Health Effects Division (USEPA 2000; D264157). The most recent drinking water exposure assessment for tetraconazole was conducted in 2014 for the proposed use on sugar beet (USEPA 2014 d ; D417463). In this assessment, EFE D recommended the upper bound estimated drinking water concentrations ( EDWCs) for tetraconazole in the surface water and groundwater in Table 4.1.

Table 4. 1

. The U pper B ound EDWCs for Tetraconazole

Drinking Water Source Crop Scenario 1

- in

- 10 year acute ( 

### μg/L ) 1

- in

- 10 year

chronic ( 

### μg/L ) 30

- year average ( 

### μg/L )
Surface Water GA Pecan 1 (aerial) 11.18

-- --

MN Sugar beet 2 (chemigation) -- * 5.50

--

NC Peanuts 1 (aerial)

-- -- 4.06

Ground Water NC Cotton 3

(pecan use) 120 NA ** 118

1 Previously reported maximum EDWCs generated using PRZM/EXAMS model for aerial (pecans) and aerial (peanuts) applications (US EPA 2008; D347085, D350213) with a revised PCA factor of 0.91.

2 Current proposed use.

3 Highest EDWCs generated using PRZM

- GW model based on a 100 year simulation of 4 foliar applications of 0.125 lb. a.i./acre for a maximum annual rate of 0.5 2 lbs a.i/A for pecans (Eminent ® ESP (EPA Reg. No.80289

- 18). Note: Value in italics denotes a 100 year simulation.

*

-- means data were available but not upper bound. **NA means data were not produced by the model.



## c. Clean Water Act Programs

Tetraconazole is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act 1 

### . No Total Maximum Daily Load (TMDL) criteria

1 http://water.epa.gov/lawsregs/lawsguidance/cwa/tmdl/

### 7

have been developed for tetraconazole

. Aquatic benchmarks have been established for tetraconazole and are available at http:// www.epa.gov/oppefed1/ecorisk_ders/aquatic_life_benchmark.htm

. Any data submitted or otherwise located as part of the registration review process may be used to update aquatic life benchmarks

, if applicable.



## 5. Environmental Fate and Transport

The physical, c hemical, environmental fate, and transport properties of tetraconazole are listed in Table 5.1

. The vapor pressure (1.0 x 10

- 6 

### mm Hg) and Henry's Law Constant (3.07 x 10

- 9 

### atm

m 3 

### /mol) of tetraconazole indicate that the compound is considered relatively non

- v olatile under field conditions (wet/dry soils and water bodies)

. Although tetraconazole has some potential to bioaccumulate in fish tissue (log Kow = 3.56), there was nearly complete elimination (> 98% of the accumulated [ 14 

### C] residues over 6 days exposure ) by day 2 of the depuration period. The bioaccumulation factor in whole rainbow trout was 39

- 42x (MRID 44751320).

Tetracon a zole does not have a single predominant route of dissipation. The compound is expected to be persistent (laboratory and field half

- l ives ranged from 63 days to more than 1 year) and slightly mobile in soil (mean Koc = 3

, 200 mL/g o.c.).

Tetraconazole is stable to hydrolysis in sterile pH 5, 7 and 9 at 25 ° C in aqueous buffer solutions (MRID 44367002). Aqueous photolysis half

- lives range from 107 days to 215 days (MRID 44367003) and soil photolysis half

- lives range from 63 day s to 204 days (MRID 45851802).

T etraconazole is stable to aerobic soil metabolism with half

- lives greater than the experimental period tested (100 days, MRID 4 5851801; 365 days; MRID 44367005). There was no data submitted for anaerobic soil metabolism.

For aquatic environments, aerobic aquatic metabolism half

- lives range from 320 days to 382 days (MRID 44751319) with anaerobic aquatic metabolism half

- lives stab le as it was greater than the experimental period tested (180 days, MRID 45840001).

Significant unextractable residues were present in soil photolysis (~22% at 112 days), aerobic soil metabolism (~16% at 365 days) and aerobic aquatic metaboli sm (~18% at 10 0 days) studies. The unextractable residues may be included in the half

- life calculation as parent tetraconazole based on the lines of evidence s (USEPA 2014e). In addition, the aerobic aquatic metabolism data show that tetraconazole partitioned from the wa ter phase into the sediment phase. CO 2 

### production in the laboratory studies was generally low (< 1.0% of applied radioactivity).

Aged column leaching studies indicate that tetraconazole has a low potential for leaching with a dependence on soil type. In s andy soil, the total residues in the leachate were up to 33 .15% of applied radioactivity within 12 inches and no residues were detected below 12 inches

. In a loamy peat soil, no residues were detected below 2 inches and the total residues in the leachate d id not exceed 0.03% of applied radioactivity.

The results of terrestrial field dissipation studies conducted in the U.S. are consistent with laboratory findings. On bare ground plots tetraconazole dissipated slowly with half

- lives

### 8

ranging from 91 days (GA ) and 222 days (CA) and did not show movement below a depth of
6

- inches (MRID 44865405). For foreign soils, dissipation half

- lives rang ed from 128 days (Italian sandy loam; MRID 44865404) to 800 days (German silty sand; MRID 44865406) and did not show move m ent below a depth of 8 inches. The se results indicate that tetraconazole has the potential to accumulate in soil with successive annual applications.

Tetraconazole has the potential to reach surface water via run

- off and spray drift and has tendency

to a ccumulate in the top soil layer and in the aquatic environment due to its persistence . Upon entering surface waters, tetraconazole is expected to readily partition from the water column into the sediment, sorb onto the sediment and then degrade very slowly (MRID 44751319)

. Tetraconazole is less likely to reach ground water due to its slight mobility in soil and has a low potenti al to contaminate ground water. However, under some environmental conditions, such as sandy soils, tetraconazole residues may reach ground water resources

.
Table 5.1. Environmental Fate Properties of Tetraconazole

Parameter Value Source/MRID #

Common name Tetraconazole

44268104 CAS number 112281

- 77

- 3
Chemical name 1

- [2

- (2,4

- Dichlorophenyl)

- 3

- (1,1,2,2

- tetrafluoroethoxy)propyl]

- H1

- 1,2,4

- triazole
Chemical Class Chemical Category Triazole Fungicide
SMILES Notation Clc1cc(Cl)ccc1C(Cn2ncnc2)COC(F)(F)C(F)F Empirical formula C 13 H 11 N 3 OCl 2 F 4 Structure

Molecular Mass (g/mol) 372.14 Water Solubility at pH 7 and 23◦C (mg/L) 159.3

Vapor Pressure at 20  C (mm Hg) 1.0 x 10

- 6 44305301

Organic Carbon Partition Coefficient (K OC ) (L/kg OC ) 3

, 200 1 44367006 47023201 Henry’s Law Constant (atm

- m 3 /mol) 3.07 x 10

- 9 calculated 2

Octanol/water partition coefficient (log Kow) 3.53 44305301

Hydrolysis (t 1/2) Stable at pH 5, 7, 9 at 25  C (8402 days at pH7; SFO) 44367002

Direct Aqueous Photolysis

(t 1/2 ) 215 days (September) 107 days (July) 44367003

### 9 Parameter Value Source/MRID #

Soil Photolysis
(t 1/2 ) 107 days (silt loam) 63 days (sand) 204 days (loamy sand) 81 days (sandy loam) 44367004

45851802

45851802

45851802

Aerobic Soil Metabolism

(t 1/2 ) > 365 days (sandy loam) > 100 days (sand) > 100 days (loamy sand) > 100 days (sandy loam) 44367005 45851801 45851801 45851801

Anaerobic Soil Metabolism (t 1/2 ) Data Gap

--

Aerobic Aquatic Metabolism (t 1/2 ) 382 days (silty loam) 320 days (sandy sediments) 44751319

Anaerobic Aquatic Metabolism (t 1/2 ) Stable ( > 180 days in tap water

- silty clay loam) 45840001

Soil Partition Coefficient (Koc) 12,209 mL g o.c.

- 1 for Loamy Sand (AR) 3755 mL g o.c.

- 1 for Sand (MO)
6

, 566 mL g o.c.

- 1 for Loamy Sand (GA) 785 mL g o.c.

- 1 for Silt Loam (ND)
1

, 244 mL g o.c.

- 1 for Clay Loam (ND)
1

, 004 mL g o.c.

- 1 for Sand (foreign) 769 mL g o.c.

- 1 for Sandy Loam (foreign) 428 mL g o.c.

- 1 for Clay (foreign)
2

, 036 mL g o.c.

- 1 for Clay Loam (foreign)
Mean = 3 , 200 mL g o.c.

- 1 47023201 47023201 47023201 47023201 47023201 44367006 44367006 44367006 44367006

Aged Soil Column Leaching Soil Type: No residues were detected below (% A.R. leachate) German Sand: 12 inches (33.15%) UK Clay: 6 inches (0.12%) UK Clay: 8 inches (0%) UK Loamy Peat: 2 inches (0.03%) UK Clay: 10 inches (0.13%) UK Clay: 4 inches (0.063%) UK Loamy Peat: 4 inches (0.021%) German Sandy Loam: 6 inches (0.37%) 45851803 44367007 44367007 44367007 44367008 44367008 44367008 44367009

Terrestrial Field Dissipation (DT 50 ) DT 50 : (No residues were detected below) Soil Type 128 days (4 inches) Italian Sandy Loam 91 days (6 inches) Georgia Loamy Sand (bare plot) 222 days (6 inches) Californian Sandy Loam (bare plot) 577 days (8 inches) German Loamy Sand (bare plot) 800 days (8 inches) German Silty Sand (bare plot) 265 days (8 inches) German Loamy Sand (bare p lot) 182 days (8 inches) German Loamy Silt (bare plot) 44865404

44865405

44865405

44865406

44865406

44865406

44865406

Bioaccumulation in Fish (BCF) 24

- 31X in edible tissues

58

- 61X for inedible tissues

39

- 42X for whole fish 44751320

### 10 Parameter Value Source/MRID # 98% eliminated by day 2 of the depuration period

1 = represents the mean Koc from 9 values (1004, 769, 428, 2036, 12209, 3755, 6566, 785, 1244).

2 = Henry's Law = (Vapor Pressure / 760) / (Water Solubility/Molecular Weight)



## a. Transformation Products A total of eight degradation products (5 major; 3 minor) were observed in aqueous and soil pho toly sis s tudies

. Due to the various naming conventions of the degradates in various studies, refer to Appendix II

, which summarizes the maximum percent formation of degradates including their structures

. 1,2,4

- triazole , a common degradate of the conazole group, was a minor degradate forming at a maximum of 8.0% in a n aqueous photolysis study (MRID 44367003 )

.



## 6. Receptor s

The receptor is the biological entity th at is exposed to the stressor. T he types of receptors that may be exposed include both aquatic and terrestrial receptors, such as birds, reptiles, mammals, amphibians, freshwater and estuarine/marine fish, non

- targ et terrestrial and aquatic invertebrates, and terrestrial and aquatic plants, etc for the agricultural uses of tetraconazole

.



## a. Effects to Aquatic Organisms

Tetraconazole is relatively soluble in water. D irect application of tetraconazole to streams, lakes, and ponds is not permitted by the product label

, however, tetraconazole residue may enter the aquatic system through spr ay drift, run off and leaching. Fish, amphibians, aquatic invertebrates and aquatic plants that live in aquatic environments are potentially exposed to tetraconazole residues in surface water and sediment.

Table 6.1 provide s a summary of the aquatic ta xonomic groups, and the available endpoints for the most sensitive surrogate species tested to characterize the potential acute and chronic ecological ef

fects of tetraconazole.

Table 6.1

. Summary of the Most Sensitive Endpoints from Aquatic Toxicity Studies for Tetraconazole
Exposure Scenario Species Exposure Duration Toxicity Reference Value Reference (Classification)
Freshwater Fish
Acute Bluegill sunfish

( Lepomis macrochirus ) 96 hours 96

- Hour LC 50 : 3.85 mg a.i./L NOAEC: 1.73 mg a.i./L

moderately toxic MRID 44367017 (Supplemental)

### 11 Rainbow trout ( Oncorhynchus mykiss ) 96 hours 96

- Hour LC 50 : ≥5.2 mg a.i./L NOAEC: 0.6 mg a.i./L (based on increased pigmentation)

moderately toxic MRID 45823204 (Supplemental)

Chronic Fathead minnow

( Pimephales promel as) 34 days NOAEC: 0.30 mg a.i./L LOAEC: 0.96 mg a.i./L (growth)

terminal growth (dry weight and length) affected at
concentrations ≥ 0.96 mg a.i./L; loss of equilibrium at concentrations ≥ 3.21 mg a.i./L MRID 45823208 (Supplemental)

Freshwater Invertebrates
Acute Waterflea

( Daphnia

magna ) 48 hours 48

- hour LC 50 : 2.63 mg a.i./L NOAEC: 0.48 mg a.i./L

moderately toxic MRID 44367018 (Supplemental)

Chronic Waterflea

( Daphnia

magna ) 21 days NOAEC: 0.19 mg a.i./L LOAEC: 0.29 mg a.i./L

Reproduction effects MRID 45823207 (Acceptable)

Estuarine/Marine Fish
Acute Sheepshead

minnow ( Cyprinodon variegatus ) 96 hours 96

- Hour LC 50 : >3.4 mg a.i./L NOAEC: 1.6 mg a.i./L

moderately toxic MRID 45823206 (Supplemental)

Chronic No data

submitted NA NA NA

Estuarine/Marine Invertebrates Acute (shrimp) Mysid shrimp

( Americamysis bahia ) 96 hours 96

- Hour LC 50 : 0.44 mg a.i./L NOAEC: 0.25 mg a.i./L

highly toxic erratic swimming and lethargy MRID 45823203 (Supplemental)

Acute (mollusk) Eastern oyster

( Crassostrea virginica ) 96 hours 96

- hour EC 50 : 1.0 mg a.i./L NOAEC: 0.81 mg a.i./L

highly toxic reduced shell deposition MRID 45823202 (Acceptable)

Chronic (Shrimp) No data

subm itted NA NA

Aquatic Plants Macrophytes Duckweed

( Lemna gibba ) 7 days EC 50 : 0.31 mg a.i./L (non

listed) NOAEC: 0.032 mg a.i./L (listed) LOAEC: 0.10 mg a.i./L

highly toxic MRID 45842201 (Acceptable)

Freshwater green alga, freshwater and marine diatom No data

submitted NA NA NA

### 12

Cyanobacteria No data

submitted NA NA NA

Benthic Organisms
Chironomid Chironomus

riparius 28 day EC 50 : 5.8 mg a.i./L NOAEC: 2.97 mg a.i./L LOAEC: 4.45 mg a.i./L MRID 46614333

Whole sediment

– chronic freshwater and saltwater invertebrates No data

submitted NA NA NA



## b. Effects to Terrestrial Organisms

Tetraconazole is stable to moderately persistent in terrestrial environments and its residue s are expected to be found in the surface soil and on f oliage (e.g., short and tall grasses, broadleaf weeds), seeds, and insects on the treated agriculture field immediately follow ing aerial or ground spraying. In addition, the spray drift, and runoff may result in transport of tet raconazole off of the target field. Birds, mammals, reptiles, and amphibians that ingest foliage, insects and/or soil invertebrates from either the treated area or off

- target areas are potentially exposed to tetraconazole residues

. These animals may be exposed to tetraconazole by a variety exposure routes, such as diet; dermal contact, direct droplet impinge ment during spray, inhalation ; and drinking water sources

.

Table 6.2 provide s a summary of the terrestrial taxonomic groups, and the available endpoints for the most sensitive surrogate species tested to characterize the potential acute and chronic ecological effects of tetr aconazole.

Table 6.2

. Summary of the Most Sensitive Endpoints from Terrestrial Toxicity Studies for Tetraconazole
Exposure Scenario Species Exposure Duration Toxicity Reference Value Reference (Classification)
Mammals
Acute (Dose

- based) Rat

( Rattus norvegicus ) Single dose LD 50 (females): 1031 mg a.i./kg bw NOAEL: 750 mg a.i./kg bw

slightly toxic MRID 44268112 (Acceptable)

Chronic Rat

( Rattus norvegicus ) 2

- generation

reproduction LOAEL: 70 mg a.i./kg diet

Reproduction NOAEL: 10 mg a.i./kg diet

Effects in offspring observed MRID 44305306 (Acceptable)

Birds
Acute (Dose

- based) Bobwhite quail

( Colinus virginianus ) Single dose LD 50 : 131 mg a.i./kg bw NOAEL: 25 mg a.i./kg bw

moderately toxic MRID 44367011 (Acceptable)

### 13

Exposure Scenario Species Exposure Duration Toxicity Reference Value Reference (Classification)
Mallard duck ( Anas platyrhynchos) 14 days LD 50 : >62.5 mg a.i./kg bw NOAEL: 62.5 mg a.i./kg bw

moderately toxic MRID 44384501

Passerine ( No data submitted ) NA NA NA

Avian reproduction Bobwhite quail

( Colinus virginianus ) 22 weeks

Reproduction LOAEL: 25

NOAEL: 1 6 mg a.i. /kg bw MRID 44751321 (Supplemental)

Mallard duck ( Anas platyrhynchos) 22 weeks LOAEL: 50 mg a.i./kg Hatchling survival and growth effected NOAEL: 10 mg a.i./kg diet

Hatchling survival and growth affected MRID 44367014 (Acceptable)

Acute (Diet

- based) Mallard duck

( Anas platyrhynchos) Acute dietary LC 50 : 382 mg a.i./kg diet NOAEC: <304 mg a.i./kg diet

highly toxic MRID 44367012 (Acceptable)

Bobwhite quail ( Colinus virginianus ) Acute dietary LC 50 : 637 mg a.i./kg diet NOAEC: <325 mg a.i./kg diet MRID 44367013 (Acceptable)

Non

- target Insects Oral Acute Honeybee

( Apis mellifera ) 48

- hour LD 50 : >130 μg a.i./bee MRID 44751322 (Acceptable) Contact Acute Honeybee

( Apis mellifera ) 96

- hour LD 50 = 63 μg a.i./bee

practically non

- toxic
Non

- guideline 4 Honeybee adult

chronic toxicity ( No data submitted) NA NA NA

Non

- guideline 4 Honeybee larval

acute and chronic toxicity ( No data submitted) NA NA NA

Non

- guideline Residues in

pollen and nectar ( No data submitted) NA NA NA

850.3040 Field or semi

field testing for pollinators ( No data submitted) NA NA NA

Plants

– Seedling Emergence
Monocot Four species

tested a Single

application EC 25 >0.1 lbs a.i./A

NOAEC = 0.1 lbs a.i./A MRID 45823209 (Acceptable) Dicot Six species

tested b EC 25 >0.1 lbs a.i./A NOAEC = 0.1 lbs a.i./A
Plants

– Vegetative Vigor

### 14

Exposure Scenario Species Exposure Duration Toxicity Reference Value Reference (Classification)

Monocot Four species

tested a Single

application EC 25 >0.1 lbs a.i./A

NOAEC = 0.1 lbs a.i./A MRID 45823210 (Acceptable) Dicot Six species

tested b EC 25 >0.1 lbs a.i./A NOAEC = 0.1 lbs a.i./A

a Monocots tested: corn ( Zea mays ) , onion ( Allium cepa ) , ryegrass ( Lolium perenne ) , and wheat ( Triticum aestivum )

. b Dicots tested: bean ( Phaseolus vulgaris ) , cabbage ( Brassica oleracea ) , lettuce ( Lactuca sativa ) , radish, tomato ( Lycopersicum esculentum ) , and soybean ( Glycine max )

.



## c. Degradates

Tetraconazole is stable through a erobic soil, anaerobic soil, and hydrolysis pathways. Several degradates were found in aqueous or soil photolysis pathway based on the submitted stud ies

. No toxicity data were submitted for any of the major degradates

. The relative aquatic toxicity is estimated by an eco logical s tructure a ctivity r e lationship program ( ECOSAR v1.11) for both major and mino r degradates. The results show that only one major degradate, FM

- 1 or SLM

- 1 (dihydro

- isoquinoline

- triazole) formed in aqueous photolysis (10.48% maximum formation at Day 4) has a similar toxicity as the parent tetraconazole

. O ther degr a dates are several order of magnitude less toxic than the tetracon a zole ( Appendix III ). T h e registration review risk assessment will only consider the parent tetraconazole because of the parent compound’s persisten ce and because all major degradates are equivalent in toxicity or less toxic

.



## d. Ecological Incidents

The ecological incident information system (EIIS) is an Office of Pesticide Programs database that houses ecological incidents that hav e been reported to the Age ncy. EIIS includes the date and location of an incident, type and magnitude of effects observed in various species, use(s) of pesticides known or suspected of contributing to the incident, and results of any chemical residue analysis or other analyses cond ucted during incident investigation. EIIS incidents are categorized according to the certainty that the incident res ulted from pesticide exposure.

The Avian Incident Monitoring System (AIMS) is a database administered by the American Bird Conservancy that contains publicly available data on reported avian incidents involving pesticide s. Incidents listed in this dat abase may also be in the EIIS. In addition to the incidents recorded in EIIS and AIMS, additional incidents are reported by registrants to t he Agency in aggregated form of incidents occurring per product per quarter recorded in an aggregated Incident Database System (IDS)

.
Searches of the Ecological Incident Information System (EIIS v. 2.1.1), Avian In cident Monitoring System (AIMS) , and t he a ggregate Inciden t Data System (IDS) were performed on
4 / 17 /1 5 . No ecological incidents were reported in any of the databases for tetraconazole

. Although incident reporting is required under FIFRA Section 6(a)(2), the absence of reports in EIIS does not indicate that the chemical has no effects on wildlife; rather, it is possible that incidents have gone unreported

.

### 15



## 7. Exposure Pathways of Concern

The environmental fate properties and use patterns of tetraconazole indicate that direct spray, spray drift, leaching to ground water, and runoff represent potential transport mechanisms to aquatic and terrestrial organisms

. Drinking water and inhalation exposure pathways were screened using the SIP (Screening Imbibition Program , v1.0 ) and STIR (Screening Tool fo r Inhalation Risk) screening methods

.
SIP was used to calculate an upper bound estimate of tetraconazole exposure via drinking water using solubility (156 mg/L), the most sensitive acute and chronic avian toxicity endpoints (bobwhite quail, LD 50 

### = 131 mg a

. i

. /kg

- bw; bobwhite quail NOAEC = 25 mg a

. i

. /kg

- diet) and the most sensitive acute and chronic mammalian toxicity endpoints (rat LD 50 

### = 1031 mg a

. i

. /kg

- bw and NOAEL = 750 mg a

. i

. /kg

- bw) ( Appendix I V Table 1 ). The model indicated that drinking

wa ter exposure alone is no t a potential concern for mammals ( Appendix I V Table 2), but it is a potential concern for birds ( Appendix I V Table 3 )

.
STIR was used to calculate an upper bound estimate of tetraconazole exposure via inhalation using molecular w eight (372.1 g/mole), vapor pressure (9.90 x 10

- 7 

### mmHg), high end application rates (aerial: 0.52 lb a

. i

. /A), most sensitive acute avian toxicity endpoint (bobwhite qua i l, LD 50 

### = 131 mg a

. i

. /kg

- bw), and most sensitive acute oral and inhalation mammalian toxicity endpoints (rat, LD 50 

### = 1031 mg a

. i

. /kg

- bw and LOAEL = 40.6 mg a

. i

. /kg/day, respectively) (Appendix V)

. The results indicated that inhalation alone is not a p otential pathway of concern for birds or mammals.

SIP and STIR are described at : http://www.epa.gov/oppefed1/models/terrestrial/index.htm

.



## 8. Analysis Plan

To address the risk hypothesis, the potential for adverse effects on the environment is estimated. The use, environmental fate, and ecological effects of tetraconazole will be characterized and integrated to assess risk. This will be accomplished using a risk quotient (ratio of exposure concentration to e ffects concentration) approach.

The Agency does not routinely include an evaluation of mixtures of active ingredients (either those mixtures of multiple active ingredients in product formulations or those in the applicator’s tank) in its risk assessments. Each active ingredient is subject to an individ ual risk assessment for a regulatory decision regarding the active ingredient on a particular use site (USEPA 2004d). EFED will consider open literature, currently available models and other lines

- of

- evidence ( e.g. , monitoring data), as available to addres s the potential for cumulative effects of formulations in the risk description of the ecological assessment for tetraconazole.

### 16

This analysis plan will be revisited and may be revised depending upon a full review of the data available in the open literatur e and the information submitted by the public in response to the opening of the Registration Review docket.



## a. Stressors of Concern

i. Ecological Risk Assessment The stressor of ecological concern for terrestrial and aquatic organisms will be tetraconazole onl y because the parent was stab le and all major degradates were less toxic with only on e exception, M14360

- dihydro

- isoquinoline

- triazole (FM

- 1, SLM

- 1), which was equally toxic to the parent ( Appendix III ) and are expected to form only in clear shallow water bodies

. Toxicity e ndpoints derived from both acute and chronic studies will be used to assess the risks for terrestrial and aquatic organisms such as birds, reptiles, mammals, amphibians, freshwater and estuarine/marine fish, non

- target terrestrial and aquatic invertebrates, and terrestrial and aquatic plants, etc.

ii. Drinking Water

If a new drinking water assessment is needed, it wil l include the parent tetraconazole only based

o n the MARC memorandum of the Health Effects Division (USEPA 20 00; D264157 )

. T he assessment will be performed based on EFED’s current guidance using appropriate s urface and groundwater models. Descriptions of a ll executable versions of current models for drinking water exposure can be obtained from http://www.epa.gov/oppefed1/models/water/

.



## b. Measures of Exposure

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

. The

p arent tetraconazole will be assessed for terrestrial and aquatic exposures

.

i. Available Monitoring Data

The Agency is aware of monitoring conducted by federal and state agencies such as U.S. Geological Survey (USGS) National Water Quality Assessment (NAWQA) Data Warehouse and California Environmental Data Exchange Network (CEDEN). This exposure data will be considered in the assessment to the extent that data on tetraconazole are available

.

### 17



## c. Measures of Effect

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



## 9. Endange red 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 Jo int Interim Approaches developed to implement the recommendations of the April 2013 National Academy of Sciences (NAS) report, (Nat ional Research Council, 2013). The NAS report outlines recommendations on specific scientific and technical issues related to the development of pesticide risk assessments that EPA and the Services must conduct in connection with their oblig ations under the ESA and FIFRA. EPA will address concerns specific to tetraconazole in connection with the development of its final registration review decision for tetraconazole

.

In November 2013, EPA, the US Fish and Wildlife Service, National Marine Fisheries (the Services), and USDA released a white paper containing a summary of their joint Interim Approaches for assessing risks to endangered and threatened (li sted) 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 assess ment shared by the agencies as a way of addressing scientific differences bet ween 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.

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 tetraconazole does not describe the specific ESA analysis, including effects determinations for specific listed species or designated critical habitat, to be conducted during regis tration review. While the agencies continue to develop a common method for ESA analysis, the planned risk assessment for the registrat ion review of tetraconazole 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 t he scientific methods being developed by the agencies have been fully vetted. Once the agencies have fully developed and implemented the scientific methods necessary to complete risk assessments for endangered and threatened (listed) species and their desi gnated critical habitats, these methods

### 18

will be applied to subsequent analyses of tetraconazole as part of completing this registration review.



## 10. Endocrine Disruptor Screening Program

T etraconazole may have adverse effects on the endocrine system based on the r esults of submitted toxicity studies in freshwater invertebrates (daphnids), birds (mallard ducks), and mammals (rats) (USEPA 2006a). Tetraconazole was not included in the first group of 67 chemicals nor the second group of 109 chemicals that will or have been issued an order to conduct Tier 1 Endocrine Disruptor Screening Program ( EDSP ) testing. For additional information the EDSP program, visit http://www.epa.gov/endo/

.



## 11. Preliminary Identification of Data Gaps

a. Environmental Fate

Table 11.1 identifies environmental fate studies by MRID that offer data for each guideline requirement, as well as study classifications and whether or not further data are needed to support the risk assessment

. In the event of new information emerging through data call

- in that requires degradate modeling, EFED will assume these degradates are stable and use QSAR modeling (E PISuite ver. 4.0) to estimate the physical and chemical properties needed for modeling inputs

. Accumulation of parent tetraconazole in the water column was demonstrated through PRZM/EXAM standard pond simulation under Florida strawberry scenario (USEPA 20 10 a , DP381443+). However, the predicted levels of accumulation (<18 ppb) in 30 years is less than the NOAEC value (32 ppb) of the most sensitive aquatic duckweed and therefore, a pond monitoring study for the potential accumulation will not be necessary.

Table 1 1.1 . Submitted Environmental Fate Data for Tetraconazole

OCSPP Guideline Description MRID Classification Data Gap Comments

835.2120 Hydrolysis 44367002 Supplemental No

--

835.2240 Photo degradation in

Water 44367003 Supplemental No

--

835.2410 Photo degradation in Soil

44367004 Supplemental No No dark controls but tetraconazole was metabolically stable in a sandy loam soil for 1 year (MRID 44367005)

4851802 Supplemental No No dark controls but < 10% applied tetraconazole degraded after 100 days (MRID 45851801)

835.4100 Aerobic Soil Metabolism 44367005 Supplemental No

--

45851801 Supplemental No

--

### 19

OCSPP Guideline Description MRID Classification Data Gap Comments

835.4200 Anaerobic Soil

Metabolism Yes These data are required under 40 CFR part 158 for terrestrial outdoor

uses. No anaerobic soil meta bolism studies were submitted. OCSPP guidance recommends that these tests be performed with four soils.

835.4300 Aerobic Aquatic

Metabolism 44751319 Acceptable No

--

835.4400 Anaerobic Aquatic

Metabolism 45840001 Supplemental Yes A single anaerobic aquatic metabolism study ha s been submitted to the Agency. OCSPP guidance recommends that

– testing be done with two sediment

- water systems with varying organic carbon content and texture. Testing in one additional sediment water system i s recommended

.

835.1230 Adsorption/Desorption 47023201 Acceptable No

--

44367006 Supplemental No Only foreign soils were studied

835.1240 Leaching 45851803 44367007 44367008 44367009 Supplemental

Supplemental Supplemental Supplemental No F oreign soils; exaggerated rate of parent compound Data are considered as adequate.

835.6100 Terrestrial Field

Dissipation 44865404

44865405 44865406 Supplemental

Supplemental Supplemental No F oreign soil; no degradate analysis no degradate analysis foreign soil; no degradate analysis

860.1380 Storage Stability in Soil

--

-- Yes Data will be used for both validate the previous terrestrial field dissipation studies and future field monitoring study if there is a need.

Storage Stability in
Water

--

-- Yes

--

850.6100 ECM/ILV

– Soil

--

-- Yes ECM and ILV studies should be submitted together in one package ECM/ILV

– Water

--

-- Yes

850.1730 Bioaccumulation in Fish

(BCF) 44751320 Supplemental No

--

### 20



## b. Ecological Effects

Table 11 .2 and Table 1 1.3 identify ecological effects studies by MRID that offer data for each guideline requirement, as well as study classifications and whether or not further data are nee ded to support risk assessment. Rationale s for non

- guideline data that are being recommende d are presented below the tables.

Table 1 1.2

. Aquatic Ecological Effects Data for Tetraconazole and Remaining Data Gaps

OCSPP Guideline Description MRID Classifications Data Gap Comments

850.1010 Freshwater invertebrate

acute toxicity 443 67018 Water flea Daphnia

magna Supplemental No

1 No chronic data are available for sal twater invertebrates

. The data are required under 40 CFR 158 because tetraconazole is mobile and stable in water (half

- life ≥ 320 days.

2 No chronic data are available for saltwater fish. The data are conditional ly required under 40 CFR 158

. Study is recommended due to tetraconazole persistence.

3 D ata for freshwater f

ish life cycle are r ecommended because of tetraconazole ’s persistence

. In addition, lines of evidence show that avian h atchling survival and growth are effected, suggesting that 850.1025 850.1035 Saltwater invertebrate

acute toxicity (mollusk) 45823202 Eastern oyster Crassostrea virginica Acceptable No

45823203 Mysid shrimp Americamysis bahia Supplemental

850.1075 Freshwater fish acute

toxicity 44367017 Bluegill sunfish Lepomis macrochirus Supplemental No

45823204 Rainbow trout ( Oncorhynchus mykiss ) Supplemental No

850.1075 Saltwater fish acute

toxicity 45823206 Sheepshead minnow Cyprinodon variegatus Supplemental No

850.1300 Freshwater invertebrate

life cycle 45823207 Water flea Daphnia

magna Acceptable No

850.1350 Saltwater invertebrate

life cycle None N/A Yes 1 (TGAI) *

850.1400 Fish early

- life stage

(Freshwater) 45823208 Fathead minnow Pimephales promel as Supplemental No

Fish early

- life stage (Saltwater) None N/A Yes 2 (TGAI)

### 21

OCSPP Guideline Description MRID Classifications Data Gap Comments

850.1500 Fish life cycle

(Freshwater fish) None N/A Yes 3 tetraconazole may affect fish hatching survival as well

.

4 T esting with two freshwater species Hyalella azteca and Chironomus tentans ; and one saltwater species Leptocheirus plumulosus is recommended to determine if there is any potential adverse effect to sediment dwelling organisms and the species sensitivity.

5 Testing is recommended for f our species, (

- a freshwater green algae, a c yanobacter i um , a freshwater diatom and an estuarine/marine diatom ) to support the risk assessment for

non

- vascular plant species. ** Non

guideline Whole sediment

–

chronic freshwater invertebrates None N/A Yes 4 (TGAI)

Whole sediment

– chronic Saltwater invertebrates None N/A Yes 4 (TGAI)

850.4400 Aquatic vascular plant

toxicity test 45842201 Duckweed Lemna gibba Acceptable No

850.4500 Freshwater green alga,

freshwater and marine diatom None N/A Yes 5 (TGAI)

850.4550 Cyanobacteria None N/A Yes 5 (TGAI)

* TGAI = technical grade active ingredient

** For a non

- guideline study

, a protocol should be submitted in advance of conducting the study. In the abse nce of the data, toxicity data for surrogate conazole fungicides (triazoles)

– starting with data for closely related pesticides and proceeding to data for less related pesticides may be used to characterize the toxicity of tetraconazole to the aquatic organism. Alternatively, if there are no data for any of the triazoles, risks of concern will be presumed

.

Table 11

. 3 

### Terrestrial Ecological Effects Data for Tetraconazole and Remaining Data Gaps

OCSPP Guideline Description MRID Classifications Data Gap Justification s

850.2100 Avian oral toxicity 44367011 Bobwhite quail Colinus virginianus Acceptable No

1 Avian acute oral toxicity data are not available for passerines. These data are required under the new 40 CFR Part 158. Mallard duck ( Anas platyrhynchos) Supplemental No

None (passerine) N/A Yes 1 (TGAI)

850.2200 Avian dietary toxicity 44367013 Bobwhite quail Colinus virginianus Acceptable No

44367012 Mallard duck
Anas platyrhynchos Acceptable No

### 22

OCSPP Guideline Description MRID Classifications Data Gap Justification s

850.2300 Avian reproduction 44751321 Bobwhite quail Colinus virginianus Supplemental No

44367014 Mallard duck
Anas platyrhynchos Acceptable No

850.3020 Honeybee adult acute

contact toxicity 44751322 Honeybee Apis mellifera Acceptable No 2 Honeybee adult chronic toxicity data are not available.

3 Acute oral toxicity data with larval bee and chronic oral toxicity data with adult and larval bee are not available. Acute and chronic oral toxicity data with larval bee may be collected in a combined study.

4 Additional data may be requested at a later d ate pending results from lower tier studies.

Please see the additional justification table. The pollinator data are required based on the Agency’s current pollinator risk assessment framework (USEPA, 2014c). ** Non

guideline (OECD 213) Honeybee adult acute

oral toxicity 44751322 Honeybee Apis mellifera Acceptable No

Non

guideline 4 Honeybee adult chronic

toxicity N one N/A Yes 2 (TGAI)

Non

guideline 4 Honeybee larval acute

and chronic toxicity N one N/A Yes 3 (TGAI)

Non

guideline Residues in pollen and

nectar None N/A Yes 4 (TEP)*

850.3040 Field or semi

- field

testing for pollinators None N/A Yes 4 (TEP)

850.4100 Seedling Emergence

and Seedling Growth 45823209 Acceptable Yes 5 (TEP) 5 Additional studies with the

maximum rate are needed because the available studies were conducted using a single application rate ( 0.1 lbs a.i./A) that is lower than the maximum single rate for pecans ( 0.13 lbs a.i./A)

. 850.4150 Vegetative Vigor 45823210 Acceptable Yes 5 (TEP)

* T EP = typical end

- use product

** For a non

- guideline study (OECD protocol is not considered as an EFED guideline) , a protocol should be submitted in advance of conducting the study. In the absence of the data, toxicity data for surrogate conazole fungicides (triazoles )

– starting with data for closely related pesticides and proceeding to data for less related pesticides may be used to characterize the toxicity of tetraconazole to th e birds, honeybees and plants. Alternatively, if there are no data for any of the triazo les, risks of concern will be presumed.

### 23

Additional justification for tetraconazole non - guideline data request s :

Study Title: Tier I

- Honeyb ee Adult Chronic Oral Toxicity Study; Rationale for Requiring the Data
No data have been submitted on the chronic toxicity of tetra c onazole to adult honey bees. A study is needed to determine the chronic toxicity of the compound to adult honey bees, including mortality and sub

- lethal effects. This study is part of EFED’s current screening

level process for deter mining potential effects to terrestrial invertebrates. Although EPA has not developed a guideline for this study and OECD has yet to finalize test guidance for chronic studies, efforts are currently underway to develop standardized guidelines for assessing effects from chronic (10

- day) exposures to adult bees in the laboratory. The registrant should submit a proposed protocol for review and approval by EFED prior to initiation of the study.

The Agency finalized its framework to assess risk to pollinators ( USEPA, 2014 c ). EPA now requires this study for all use sites where potential exposure to pollinators may occur. Registrants may request a waiver of the study if use practices significantly restrict exposure of the pesticide to bees. Practical Utility of the Data How will the data be used and how could the data impact the Agency’s future decision

making?
The 10

- day toxicity study with young adult bees provides no

- observed adverse effect level (NOAEL) and lowest

- observed adverse effect level (LOAEL) for as sessing chronic effects. Data obtained from this study will be used in estimating chronic risk to individual adult bees. Risk estimates based on these data will be considered along with other lines of evidence to determine whether higher

- tier studies are n eeded at the whole colony level.

These data are needed for the registration review risk assessment and for future endangered species assessments. The data would allow the Agency better characterize the potential for risk to insects (including beneficial pollinators) from the use of tetra c onazole. Th e s e data may help the Agency determine whether any mitigations are needed. If the registration review and any future endangered species risk assessments are performed without these data, the Agency

may have to assume that tetra c onazole "may affect" insects, including bees and beneficial pollinators, directly (and endangered species from other taxa indirectly), and uses of

tetra c onazole might need to be restricted in areas where pollinators could be exposed.

S tudy Title: Tier 1

- Larval Honeybee Acute and Chronic Oral Exposure Rationale for Requiring the Data Developing bee brood (i.e., larvae and pupae) can be exposed to tetraconazole through residues brought back to the colony by worker bees foraging in areas where tetraconazole has been applied. While larvae are typically fed royal or brood jelly during their early stages of development, worker bee (females) and drone (males) larvae are also fed pollen/honey (bee bread) d irectly by in

- hive nurse bees. EPA guidance (USEPA 2014 c ) on assessing the risk of

### 24

pesticides to bees identifies a suite of laboratory

- based studies that serve as the foundation for screening chemical for potential ac ute and chronic effects to larval bees. Practical Utility of the Data
How will the data be used?
The 21

- day larval toxicity study 1 

### under development by OECD provides both acute and chronic toxicity data on developing bee brood and will yield a median lethal dose (LD50) for assessing acute toxicity during the early part of the study as well as a 21

- day no

- observed
adverse effect level (NOAEL) and lowest

- observed adverse effect level (LOAEL) for assessing chronic effects. Alternatively, registrants may submit a separate acute (single dose) larval toxicity study following OECD Guideline 237 2 

### as well as the 21

- day repeat dose
chronic toxi city study to address both acut e and chronic larval endpoints. Effects on survival and development (adult bee emergence) from repeat exposures to the active ingredient will be used in estimating chronic risk to individual bro od. A protocol for the 21

- day l arval toxicity test should be submitted to the Agency for review before commencing the study and should include provisions for measuring the concentration of tetraconazole in the actual diet of the honeybee.

How could the data impact the Agency’s future d ecision

- making? Effects on survival and development from repeat exposures to the active ingredient will be used in estimating acute and chronic risk to individual brood. Risk estimates based on these data will be considered along with other lines of eviden ce to determine whether higher

- tier studies are needed at the whole colony level. These data are needed for the registration review risk assessment and for future endangered species assessments. The data would allow the Agency better characterize the poten tial for risk to insects (including beneficial pollinators) from the use of tetraconazole. These data may help the Agency determine whether any mitigations are needed. If the registration review and any future endangered species risk assessments are perfor med without these data, the Agency may have to assume that tetraconazole "may affect" insects, including bees and beneficial pollinators, directly (and endangered species from other taxa indirectly), and uses of tetraconazole might need to be
restricted in areas where pollinators could be exposed.

[1] Draft guidance for the 21

- day larval toxicity study is available

at: http://www.oecd.org/env/ehs/testing/Draft_GD_honeybees_rep_exp_for_2nd_CR_25_November_2013.pdf

[2] OECD Guideline 237 is available at: http://www.oecd

ilibrary.org/docserver/download/9713171e.pdf?expires=1407449911&id=id&accname=guest&checksum=E67BEDEB01DB12D815E858CB45A 989FB



### Study Title: Pollen/Nectar Residue Sampling (if it is requested by the Agency at later time) Rationale for Requiring the Data As a systemic fungicide, tetraconazole is broadcast sprayed and b ees can be exposed to pesticides through multiple pathways including contact with sprays and dusts and through ingestion of residues in food/water (e.g., pollen/nectar and water used to maintain colony temperature). Worker bees foraging on flowers for pollen and nectar can be exposed to residues in pollen and nectar either through direct and indirect contamination of these matrices by f

oliar sprays and /or dusts , as well as plant translocation (flower pollen and nectar

.

### 25

Residues can in turn be brought back to bee colonies where in

- hive bees including young adult and developing brood (i.e., eggs, larvae and pupae) may be exposed. EPA guida nce on assessing the risk of pesticides to bees identifies a tiered process where the initial screen is based on a suite of acute and chronic laboratory studies ind ividual adult bees and larvae. If screening

- level assessment indicates potential chronic ris ks to individual bees, then higher

tier, semi

- field testing studies may be required to examine potential effects at the colony
level. Tetraconazole may be applied to a variety of crops that rely on insect pollination. Residues on these crops can provide a route of exposure to foraging pollinators. Practical Utility of the Data
How will the data be used? If risk concerns are identified for any bee life stage, then pollen/nectar residue information may be needed to refine the assessment to bees.

How could the data impact the Agency’s future decision

- making? Risk estimates based on these data will be considered along with other lines of evidence to determine whether higher

- tier studies are needed at the whole

- colony level to more precisely
characterize the effects of real

- world application.

Study Title: Whole sediment: Chronic fresh and salt water invertebrates

– TGAI with Hyalella azteca and Leptocheirus plumulosus Rationale for Requiring the Data
C hronic sediment toxicity test for the freshwater in vertebrate midge ( Chironomus riparius )
ha s been submitted

. However, additional benthic species are required to satisfy the Agency’s updated data requirements for outdoor uses under 40 CFR Part 158

. Based on the current use patterns, b enthic organisms may be exposed to run

- off or spray drift from tetraconazole uses

. Because tetraconazole has tendency to accumulate in surface water and sediment due to its persistence, a dditional test with two freshwater species Hyalella Azteca and Chironomus

tentans, and four saltwater species Ampelisea abdita, Eohaustorius estuaries, Rhepoxynius
abroni us and Leptocheirus plumulosus for potential differential sensitivity among sediment organisms is required for TGAI. A protocol should be submitted in advance of conducting the study.

Practical Utility of the Data
How will the data be used? Data from sediment toxicity studies will be used to estimate potential risks to benthic organisms associated with uses of tetraconazole . The data will reduce uncertainties associated with the current risk assessment for benthic species and will improve our understanding of the potential effects of tetraconazole on aquatic ecosystems.

How could the data impact the Agency’s future decision

- making?
Available data comparison will allow a vigorous assessment of registered tetraconazole and
determine if uses pose a risk of adverse effects to non

- target benthic organisms above the Agency Level of Concern. The lack of these data will limit the fl exibility the Agency and

### 26

registrants have in coming into compliance with the Endangered Species Act, and could r esult
in use restrictions for tetraconazole which may otherwise be avoided, or which are unnecessarily severe

.



## 12. References

USEPA. 2000. Tetraconazole. Results of the HED Metabolism Assessment Review Committee (MARC) Meetings Held on 07

- and 14

- MAR

- 2000. Chemical 120603. Barcode D264157. Case 290888. Submission S556768.

USEPA. 2004a

. Preliminary Risk Assessment for Section 3

- Use of Tetraconazole on Sugar beets in Seven States to Control Cercospora Leafspot

. DP Barcode: 302899

. 47 pp.

USEPA. 2004b. Tier II Drinking Water Assessment for the Use of Tetraconazole on Sugar beets. DP Barcode: 302899. 11pp.

USEPA. 2004c. Revised Tier II D rinking Water Assessment for the Use of Tetraconazole on Sugar beets

. DP Barcode: 302899. 11pp.

USEPA. 2004d. Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs. Office of Prevention, Pesticides, and Toxic Substances. Office of Pesticide Programs. Washington, D.C. January 23, 2004.

USEPA. 200 5

. 

### Environmental Fate and Effects Division Risk Assessment for the Section 3 Registration of Tetraconazole.

– New Chemical. DP Barcode : 313005. 129pp.



### U SEPA. 200 6 a

. Environmental Fate and Effects Division Risk Assessment for the Section 3 New Use Registration of Tetraconazole

. DP Barcode s : 331424, 321742, 323683, 331686

, 321632, 322229, 325324 , and 328065

. 339 pp.

USEPA. 2006b. Tetraconazole (Parent Only) Drinking Water Assessment in Support of Registration Actions for Uses on Peanuts, Pecans, Sugar Beets, Soybeans, and Turf. DP Barcodes: 321622, 321742, and 331420. 65pp.

USEPA. 2008 a

. Environmental Fate and Effects Division Risk Assessment for the Section 3 New Use Registration of Tetraconazole

. DP Barcode: D350213

. 118 pp.

USEPA. 2008b. Tetraconazole (Parent Only) Drinking Water Assessment in Support of Registration Actions for Use on Grapes, and Application Reduction for Pecans. DP Barcodes : 347085 and 350213. 21pp

USEPA. 201 0 a

. Ecological Risk Assessment for the proposed new use of Tetraconazole on Small Fruit Vine Climbing Subgroup 13

- 07F (except fuzzy kiwifruit), Low Growing Berry Subgroup 13

- 07G, and Corn

. DP Barcodes: 380619, 381443, and 381446

. 78 pp.

### 27

USEPA. 2010b. Tier II Drinking Water Exposure Assessment to Establish Tolerances of Tetraconazole on Small Fruit Vine Climbing Subgroup 13

- 07F, Low Growing Berry Subgroup 13

- 07G and Corn. DP Barcodes: 380619 and 381445

USEPA. 2014a. Tetraconazole S creening L evel Usage A nalysis (SLUA)

. Biological and Economic Analysis Division, Office of Pesticide Programs, United States Environmental Protection Agency.

USEPA. 2014 b . Ecological Risk Assessment for Tetraconazole in Response to Eminent VP Label Amen dment to Increase Use Rate in Sugar beet. DP Barcodes: 416108, 417462 . 12

pp

.
USEPA. 2014c. Guidance for Assessing Pesticide Risks to Bees. Environmental Fate and Effects Division, Office of Pesticide Programs, United States Environmental Protection Agenc y. 59pp.

USEPA. 2014d. Tier II Drinking Water Assessment for the Proposed Tetraconazole Use on Sugar beet. DP417463. 13pp.

USEPA. 2014e. Guidance for Addressing Unextracted Residues in Laboratory Studies. Environmental Fate and Effects Division, Office of Pesticide Programs, United States Environmental Protection Agency. 24pp.

Environmental Fate Bibliography

MRID Citation Reference

44367002 Valcamonica, C.; Pizzingrilli, G.; Guarnieri , R. (1988) (Carbon

14)

- M 14360 Hydrolysis. Unpublished study prepared by Agrimont SpA. 23 p.

44367003 Pizzingrilli, G.; Rizzo, F. (1995) Photodegradation of ((carbon 14)

-

Triazole ) Tetraconazole in pH 7 Buffer Solution: Lab Project Number: R/ABT.94.01. Unpublished study prepared by Isagro Ricerca S.r.l. 99 p.

45080901 Pizzingrilli, G.; Scacchi, A. (2000) Degradation of ((carbon

- 14)

- U

Triazole) M 14360 on Soil Irradiated with Sun Light or Xenon Lamp (Pilot Study): Lab Project Number: R/ABT. 93.03. Unpublished study prepared by ISAGRO Srl. 27 p.

44367004 Pizzingrilli, G.; Scacchi, A.; Castoldi, F. (1995) Aerobic Soil

Metabolism of ((carbon 14)

- U

- Triazole) Tetraconazole (Under Sunl ight): Lab Project Number: R/ABT.94.10. Unpublished study prepared by Isagro Ricerca S.r.l. 119 p.

### 28

44367005 Waller, R. (1991) Aerobic Soil Metabolism of the Triazole

Fungicide M

- 14360: Lab Project Number: 89

- 0245: 2047

- 89

- 0245

- EF

- 002: REPORT 14360. Unpub lished study prepared by Ricerca, Inc. 280 p.

45851801 Scacchi, A.; Pizzingrilli, G. (1995) Aerobic Soil Degradation of

(Carbon 14)

- Tetraconazole in Three German Standard Soils: Lab Project Number: R/ABT.95.01. Unpublished study prepared by Isagro Ricerc a S.r.l. 103 p.

45851802 Scacchi, A.; Pizzingrilli, G. (1996) Aerobic Soil Degradation of

((Carbon 14)

- U

- Triazole) Tetraconazole in Three German Standard Soils Under Sunlight: Lab Project Number: R/ABT.95.03. Unpublished study prepared by Isagro Ricerca S.r.l. 187 p.

45840001 Scacchi, A.; Oriolo, D.; Pizzingrilli, G. (2002) Anaerobic Aquatic

Metabolism of (Carbon 14)

- Tetraconazole: Lab Project Number: MEF.01.12. Unpublished study prepared by Isagro Ricerca Srl. and Agvise Laboratories, Inc. 155 p.

447 51319 Lewis, C. (1995) (Carbon

- 14)

- Tetraconazole: Degradation and

Retention in Water

- Sediment Systems: Lab Project Number: 1320/1

- 1015: P9312D. Unpublished study prepared by Corning Hazleton. 102 p.

44367006 Pizzingrilli, G.; Scacchi, A. (1993) Adsorption

- Desorption of the

Fungicide ((carbon 14)

- U

- Triazole) M14360 in Soil: Lab Project Number: R/ABT.93.04. Unpublished study prepared by Isagro S.r.l. 86 p.

44367007 Pizzingrilli, G.; Guarnieri, R. (1990) Soil Column Leaching on

Fungicide (carbon 1 4)

- M14360: Lab Project Number: R/ABT.90.04. Unpublished study prepared by Agrimont. 33 p.

44367008 Pizzingrilli, G.; Guarnieri, R. (1990) Soil Column Leaching on

Fungicide Triazole (carbon 14)

- M 14360: Lab Project Number: R/ART.90.09. Unpublished study p repared by Agrimont. 33 p.

44367009 Pizzingrilli, G.; Guarnieri, R. (1991) Soil Column Leaching on

(carbon 14)

- M 14360: Lab Project Number: R/ABT.91.04. Unpublished study prepared by Agrimont. 29 p.

45851803 Castoldi, F.; Pizzingrilli, G. (1995) Soil C olumn Leaching After

Ageing (Under Sunlight) of ((Carbon 14)

- U

Triazole)Tetraconazole: Lab Project Number: R/ABT.95.04. Unpublished study prepared by Isagro Ricerca S.r.l. 100 p.

47023201 Scacchi, A.; Oriolo, D. (2006) Adsorption

- desorption of 14

-

Carbon

- Tetraconazole in Five American Soils. Project Number: MEF/06/01. Unpublished study prepared by Isagro Ricerca S.r.l. 328 p.

### 29

44367010 Hattermann, D. (1997) Terrestrial Field Dissipation of LX 1380

- 01

(Tetraconazole) Applied to Bareground in California and Georgia: Interim Report: Lab Project Number: 38023D003: AGR 94/970887: 1641

- 95

- 380

- 021E

- 09. Unpublished study prepared by Huntingdon Life Sciences Ltd. 233 p.

44865404 Zini , G. (1998) Analysis of Tetraconazole Residues in Soil: Final

Report: Lab Project Number: 2226. Unpublished study prepared by Isagro Ricerca. 99 p.

44865405 Hattermann, D. (1999) Terrestrial Field Dissipation of

Tetraconazole Applied to Bare Ground in Ca lifornia and Georgia: Final Report: Lab Project Number: 38023D003: AGR 94C/984988: AGR 94A/971754. Unpublished study prepared by Landis International. 331 p.

44865406 Bieber, W.; Jonas, W. (1999) Field Study: Dissipation of

Tetraconazole from Four Agricu ltural Field Soils in Germany: Lab Project Number: NA 92 9822/1: NA 92 9752. Unpublished study prepared by NATEC Institut. 131 p.

45320901 Zini, G. (2000) Tetraconazole Residues in Rotational Crops After

Treatment of Bare Soil: Lab Project Number: GZ0100

. Unpublished study prepared by Isagro Ricerca S.r.l. 661 p.

45320902 Zini, G. (2000) Tetraconazole Residues in Rotational Crops

Following Three Years of Consecutive Applications to Primary Treated Crops: Lab Project Number: GZ0200. Unpublished study

pre pared by Isagro Ricerca S.r.l. 1161 p.

44751302 Baugher, D. (1999) Chronic and Acute Dietary and Drinking Water

Exposure and Risk Assessments for Tetraconazole Used on Bananas, Plantains, and Sugar beets: Lab Project Number: 99004/TET. Unpublished study prepared by EXP Corporation. 20

p.

46614327 Winkler, V. (2005) Tier II Drinking Water Assessment for the Use

of Tetraconazole on Soybeans. Project Number: 060705. Unpublished study prepared by Isagro S.p.A. 19 p.

46614329 Winkler, V. (2005) Tetraconazole Ground and Surface Water

Monitoring by the Minnesota Department of Agriculture. Project Number: 061605. Unpublished study prepared by Isagro S.p.A. and Minnesota Department of Agriculture. 180 p.

46653901 Winkler, V. (2005 ) Addendum to "Tetraconazole Ground and

Surface Water Monitoring by the Minnesota Department of Agriculture" (MRID 46614329). Project Number: 061605/ADDENDUM. Unpublished study prepared by Isagro S.P.A., BASF Corporation and Syngenta Crop Protection, Inc. 34

p.

### 30

46706303 Winkler, V. (2005) Effects of Foliar Dissipation and

Canopy/Interception Binding on Tier II Drinking Water Assessments for Use of Tetraconazole on Sugar Beets. Project Number: 120105. Unpublished study prepared by Isagro S.P.A. 21

p.

46890 601 Winkler, V. (2006) Tetraconazole Surface Water Monitoring by the

Minnesota Department of Agriculture 2005 Results and Assessment. Project Number: 071706. Unpublished study prepared by Isagro S.P.A. 33 p.

Ecological Effect Bibliography

MRID Citation R eference

44367011 Hakin, B.; Rodgers, M.; Anderson, A. et al. (1992) M 14360: Acute

Oral Toxicity (LD50) to Bobwhite Quail: Lab Project Number: AGR 83/911248. Unpublished study prepared by Huntingdon Research Centre Ltd. and EniChem Agricoltura S.p.a . 36 p.

44384501 Hakin, B.; Anderson, A. (1990) Acute Oral Toxicity (LD50) of M

14360 to the Mallard Duck: Lab Project Number: AGR 65/891836: AGR/65. Unpublished study prepared by Huntingdon Research Centre Ltd. 31 p.

44367012 Hakin , B.; Rodgers, M.; Anderson, A. et al. (1989) The Dietary

Toxicity (LC50) of M 14360 to the Mallard Duck: Lab Project Number: AGR 64/89882: AGR/64. Unpublished study prepared by Huntingdon Research Centre Ltd. and Agrimont SpA. 31 p.

44367013 Hakin, B.; Rodgers, M.; Anderson, A. et al. (1989) The Dietary

Toxicity (LC50) of M 14360 to the Bob White Quail: Lab Project Number: AGR 66/89883: AGR/66. Unpublished study prepared by Huntingdon Research Centre Ltd. and Agrimont SpA. 31 p.

44367014 Johnson, A. (1 997) Tetraconazole: Reproduction in the Mallard

Duck: Lab Project Number: AGR 92/961928: AGR 92. Unpublished study prepared by Huntingdon Research Centre Ltd. 207 p.

44367015 Johnson, A. (1997) Tetraconazole: Effects on Reproduction in

Bobwhite Quail: La b Project Number: AGR 93/961929: AGR 93. Unpublished study prepared by Huntingdon Research Centre Ltd. 246 p.

### 31

44751321 Johnson, A. (1998) Tetraconazole Effects on Reproduction in

Bobwhite Quail: Lab Project Number: AGR101: AGR101/973413. Unpublished stud y prepared by Huntingdon Life Sciences Ltd. 225

p.

44367016 Douglas, M.; Sewell, I.; Macdonald, I. (1989) The Acute Toxicity

of M14360 Technical to Rainbow Trout (Salmo gairdneri): Lab Project Number: AGR 71/(C)/89821. Unpublished study prepared by Hunti ngdon Research Centre Ltd. and Agrimont SpA. 22 p.

44367017 Douglas, M.; Sewell, I.; Macdonald, I. (1989) The Acute Toxicity

of M14360 Technical to Bluegill Sunfish (Lepomis macrochirus): Lab Project Number: AGR 71 (D)/89803. Unpublished study prepared b y Huntingdon Research Centre Ltd. and Agrimont SpA. 22 p.

45823204 Albuquerque, R. (2001) Tetraconazole Technical: Acute Toxicity

to Rainbow Trout: Lab Project Number: IGA 014: IGA 014/014028. Unpublished study prepared by Huntingdon Life Sciences Ltd. 37 p. {OPPTS 850.1075}

45823205 Albuquerque, R. (2002) Tetraconazole Technical: Acute Toxicity

to Fish (Bluegill Sunfish): Lab Project Number: IGA 015: IGA 015/014029: 17028. Unpublished study prepared by Huntingdon Life Sciences Ltd. 41 p. {OPPTS 850.1075}

44367018 Douglas, M.; Sewell, I.; Macdonald, I. (1989) The Acute Toxicity

of M14360 Technical to Daphnia magna: Lab Project Number: AGR 71(A)/89802. Unpublished study prepared by Huntingdon Research Centre Ltd. and Agrimont SpA. 22 p.

44367019 Douglas, M.; Bell, G.; Macdonald, I. (1989) An Assessment of the

Effects o f M14360 Technical on the Reproduction of Daphnia magna: Final Report: Lab Project Number: AGR 71(B)/891053. Unpublished study prepared by Huntingdon Research Centre Ltd. and Agrimont SpA. 65 p.

45823201 Albuquerque, R. (2001) Tetraconazole Technical: Ac ute Toxicity

to Daphnia magna: Lab Project Number: IGA 016: IGA 016/014030. Unpublished study prepared by Huntingdon Life Sciences Ltd. 38 p. {OPPTS 850.1010}

45823202 Drottar, K.; Kendall, T.; Krueger, H. (2001) Tetraconazole: A 96

-

Hour Shell Deposition Test with the Eastern Oyster (Crassostrea virginica): Final Report: Lab Project Number: 468A

- 103. Unpublished study prepared by Wildlife International, Ltd. 40 p. {OPPTS 850.1025}

45823203 Blankinship, A.; Drottar, K.; Palmer, S.; et al. (2002)

Tetracon azole: A 96

- Hour Flow

- Through Acute Toxicity Test with the Saltwater Mysid (Americamysis bahia): Final Report: Lab

### 32 Project Number: 468A

- 101C. Unpublished study prepared by Wildlife International, Ltd. 41 p. {OPPTS 850.1035}

45823206 Blankinship, A.; Drottar, K.; Kendall, T.; et al. (2001)

Tetraconazole: A 96

- Hour Flow

- Through Acute Toxicity Test with the Sheepshead Minnow (Cyprinodon variegatus): Final Report: Lab Project Number: 468A

- 102. Unpublished study prepared by Wildlife International, Ltd. 41 p. {OPPTS 850.1075}

45823207 Albuquerque, R. (2002) Tetraconazole Technical: Prolonged

Toxicity to the Daphnia magna: Lab Project Number: IGA 017: IGA 017/014031. Unpublished study prepared by Huntingdon Life Sciences Ltd. 53 p. {OPPTS 850.1300}

458232 08 Albuquerque, R. (2002) Tetraconazole Technical: Fish Early Life

Stage Toxicity Test for Fathead Minnow (Pimephales promelas): Lab Project Number: IGA 018: IGA 018/022558: 16499. Unpublished study prepared by Huntingdon Life Sciences Ltd. 80 p. {OPPTS 85 0.1400}

45823209 Porch, J.; Martin, K.; Krueger, H. (2001) Eminent 125 SL: A

Toxicity Test to Determine the Effects of the Test Substance on Seedling Emergence of Ten Species of Plants: Final Report: Lab Project Number: 468

- 101A. Unpublished study prepar ed by Wildlife International, Ltd. 54 p. {OPPTS 850.4100}

45823210 Porch, J.; Martin, K.; Krueger, H. (2001) Eminent 125 SL: A

Toxicity Test to Determine the Effects of the Test Substance on Vegetative Vigor of Ten Species of Plants: Final Report: Lab
Pr oject Number: 468

- 102A: 468

- 102. Unpublished study prepared by Wildlife International, Ltd. 75 p. {OPPTS 850.4150}

45842201 Hertl, J. (2000) Toxicity of Tetraconazole Technical to the Aquatic

Plant Lemna gibba in a Growth Inhibition Test: Final Report
Re vision No. 1: Lab Project Number: 7240240: 7240240A. Unpublished study prepared by Institut fur Biologische Analytik und Consulting IBACON GmbH. 68 p. {OPPTS 850.4400}

46409401 French, J. (2004) Toxicity of Tetraconazole Technical to the

Aquatic Plant Le mna gibba in a Growth Inhibition Test [MRID 45842201] Addendum

- Raw Data. Project Number: IBACON/7240240. Unpublished study prepared by Institut fuer Biologische Analytik und Consulting IBACON. 11 p.

44751322 Schmitzer, S. (1997) Laboratory Testing for T oxicity (Acute

Contact and Oral LD50) of Tetraconazole Technical (M14360) to Honey Bees (Apis mellifera L.)(Hymenoptera, Apidae): Lab Project Number: 2290036. Unpublished study prepared by Institut fur Biologishe Analytik. 28 p.

### 33

46614304 Zini , G. (1998) Analysis of Residues of Tetraconazole in

Overlaying Water, Pore Water and Sediment from the Toxicity Test on Sediment

- Dwelling Chironomus riparius. Project Number: 2234. Unpublished study prepared by Tetraco Srl. 2234 p.

46614305 Wetton, W. (1 997) Tetraconazole tech (M14360) Acute Toxicity to

Earthworms (Eisenia foetida). Project Number: 574/004. Unpublished study prepared by Safepharm Laboratories, Ltd. 33 p.

46614306 Luhrs, U. (2002) Tetraconazole Tech (M14360) Acute Toxicity to

Earthworms ( Eisenia foetida). Project Number: 15601022. Unpublished study prepared by Institut fuer Biologische Analytik und Consulting IBACON. 32 p.

46614333 Heintze, A. (1998) Assessment of Side Effects of Tetraconazole

Tech. on the Larvae of the Midge, Chironomus riparius with the Laboratory Test Method. Project Number: 97244/01/ASCR. Unpublished study prepared by GAB Biotechnologie Gmbh. 76 p.

### 34



## Appendix I

. Tetraconazole Uses and Application Rates

1 NS

– Not specified. Up to 4 applications per year may be assumed

. 2 NS

– Not specified. Up to 4 cro p cycle per year may be assumed.

3 NDC

– No Dose Conversion

Use (Registration No.) Maximum Single Application Rate lb ai Maximum

Number of Applications per
year (minimum application interval in days unless specified ) 1 Maximum

Annual Applicatio n Rate in lbs of a

. i

. 2 Method of Application

13

- 07F. Small fruit vine climbing subgroup, except fuzzy kiwifruit 13

- 07G. Low growing berry subgroup (Reg # 80289

- 8) 0.0 408 NS NS Broadcast Chemigation

Corn (POP) (Reg # 10163

- 332, 80289

- 7, 66330

- 422) 0.0903 NS 0.0903 Broadcast Chemigation Corn (Field) (Reg # 10163

- 332, 80289

- 7, 66330

- 422) 0.0894 NS 0.0894

Peanuts (Reg # 60063

- 12, 80289

- 18) 0.1061 NS NS Broadcast Chemigation

Pecan (Reg # 60063

- 12, 80289

- 18) 0.1306 NS NS Broadcast Chemigation High volume spray (dilute) Low volume spray (concentrate) Soybeans (Reg 80289

— 20, 10163

- 332, 80289

-- 7) 0.0752 2 (15) 0.1505 Broadcast Chemigation 0.0753 2 (15) 0.150 9 Soybeans (Reg # 7969

- 361) NDC 2 2 NS Broadcast

Soybeans (Reg # 66330

- 422) NS 2 NS Broadcast Chemigation

Sugar Beet (Reg # 60063

- 12) 0.1061 NS NS Broadcast Chemigation High volume spray (dilute) Low volume spray (concentrate)

Sugar Beet (Reg # 80289

- 18) 0.102 2 0.204 Broadcast Chemigation High volume spray (dilute) Low volume spray (concentrate)

### 35



## Appendix II

. Tetraconazole Transformation Products

Code Name/ Synonym Chemical Name Chemical Structure Study Type MRID Maximum
Formation (% Applied) and Day Observed During Study Final Formation*

(% Applied) And Study Length

PARENT

Tetraconazole IUPAC Name : 1

- [2

- (2,4

-

Dichlorophenyl)

- 3

- (1,1,2,2

- tetrafluoroethoxy)propyl]

- H1

- 1,2,4

- triazole

CAS Number: 11281

- 77

- 3

Molecular Weight: 372.14 g/mol

Chemical Formula: C 13 H 11 N 3 OCl 2 F 4

SMILES: Clc1cc(Cl)ccc1C(Cn2ncnc2)COC(F) (F)C(F)F Parent structure shown for reference

TRANSFORMATION PRODUCTS

1,2,4

- Triazole

T

FM

- 7

SLM

- 3 IUPAC Name:

4H

- 1,2,4

- triazole

Molecular Weight: 69.07 g/mol

Chemical Formula: C 2 H 3 N 3 Aqueous Photolysis 44367003 8.01 (22 days) 7.42 (30 days)
Soil Photolysis 44367004 3.67 (112 days) 3.67 (112 days)
Soil Photolysis 45851802 6.88 (100 days) 3.73 (200 days)

### 36 Code Name/ Synonym Chemical Name Chemical Structure Study Type MRID Maximum
Formation (% Applied) and Day Observed During Study Final Formation*

(% Applied) And Study Length

SMILES:

C1=NC=NN1
1,2,4

- TRIAZOLE CONJUGATES OF TOXICOLOGICAL CONCERN
1,2,4

- Triazole
Acetic Acid

TAA

SLM

- 6 IUPAC Name:

2

- (1H

- 1,2,4

- triazol

- 1

- yl)acetic
acid
Chemical Formula: C 4 H 5 N 3 O 2 Molecular Weight: 127.038

SMILES: c1ncn(n1)CC(=O)O Soil Photolysis 44367004 4.89 (112 days) 4.89 (112 days)

Soil Photolysis 45851802 14.24 (150 days) 11.04 (200 days)

FM

- 1

SLM

- 1 M14360

- dihydro

- isoquinoline

triazole
Chemical Formula:

C 13 H 10 Cl 1 F 4 N 3 O Molecular Weight: 335.69

SMILES: C12c3c(C(COC(F)(F)C(F)F)CN1N=C N=2)ccc(Cl)c3 Aqueous Photolysis 44367003 10.48 (4 days) 7.22 (30 days)

Soil Photolysis 44367004 0.91 (90 days) 0.57 (112 days)

FM

- 8

M14360

- alcohol

SLM

- 2 2

- (2,4

- dichlorophenyl

- 3

- (1H

1,2,4

- triazol

- 1

- yl)

- 1

- propanol
Chemical Formula: C 11 H 11 Cl 2 N 3 O Molecular Weight: 272.14

SMILES: Clc1cc(Cl)ccc1C(Cn2ncnc2)COH Aqueous Photolysis 44367003 9.25 (30 days) 9.25 (30 days)

Soil Photolysis 44367004 4.30 (30 days) 1.47 (112 days)

Soil Photolysis 45851802 14.98 (30 days) 9.27 (200 days)

### 37 Code Name/ Synonym Chemical Name Chemical Structure Study Type MRID Maximum
Formation (% Applied) and Day Observed During Study Final Formation*

(% Applied) And Study Length

FM

- 5 Tetrafluoroethoxy

- trizolyl

isobutanoic acid
Chemical Formula: C 8 H 11 F 4 N 3 O 3 Molecular Weight: 273.19

SMILES: C(=O)(O)C(CN1C=NC=N1)COC(F)( F)C(F)F Aqueous Photolysis 44367003 11.92 (30 days) 11.92 (30 days)

FM

- 4 Hydroxy

- triazoyl

- isobutanoic acid

Chemical Formula: C 6 H 11 N 3 O 3 Molecular Weight: 173.17

SMILES: C(=O)(O)C(CN1C=NC=N1)CO Aqueous Photolysis 44367003 16.73 (22 days) 14.26 (30 days)

M14360

- acid

SLM

- 4 2

- (2,4

- dichlorophenyl

- 3

- (1H

1,2,4

- triazol

- 1

- yl)

- 1

- propionic
acid
Chemical Formula: C 11 H 11 Cl 2 N 3 O 2 Molecular Weight: 288.14

SMILES: HC(C(c1c(Cl)cc(Cl)cc1)C(=O)O)N1

C=NC=N1 Soil Photolysis 44367004 8.88 (112 days) 8.88 (112 days)

Soil Photolysis 45851802 8.37 (150 days) 6.02 (200 days)

M14360

- DFA

SLM

- 5 5

- (2,4

- dichlorophenyl

- 2,2

-

difluoro

- 6

-- (1H

- 1,2,4

- triazol

- 1

- yl)

- 3

- oxahexanoic acid
Chemical Formula:

C 13 H 13 Cl 2 F 2 N 3 O 3 Soil Photolysis 44367004 6.07 (30 days) 3.17 (112 days)

Soil Photolysis 45851802 6.49 (60 days) 4.07 (100 days)

### 38 Code Name/ Synonym Chemical Name Chemical Structure Study Type MRID Maximum
Formation (% Applied) and Day Observed During Study Final Formation*

(% Applied) And Study Length

Molecular Weight: 368.17

SMILES: C(=O)(O)C(F)(F)OCC(c1c(Cl)cc(Cl)c c1)CN1C=NC=N1

Non

- Extractable Radioactivity Soil Photolysis 44367004 21.97 (112 days) 21.97 (112 days)

Aerobic Soil Metabolism 44367005 16.10 (365 days) 16.10 (365 days)

Aerobic Soil Metabolism 45851801 8.17 (70 days) 6.92 (100 days)
Aerobic Aquatic Metabolism 44751319 18.35 (100 days) 18.35 (100 days)
Anaerobic Aquatic Metabolism 45840001 5.44 (93 days) 3.08 (180 days)

Bold indicates maximum % formation percentage of degradate Major degradates that continued to increase by study termination include FM

- 5.

### 39



## Appendix III. Comparative Aquatic Toxicity of Tetraconazole and 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 **

invertebrate 96

- hr acute LC 50 

### (mg/L) Vascular

plant 7

- day EC 50 

### (μg/L) Non

vascular plant 96

- hr EC 50 

### (μg/L) Experimental Data
Tetraconazole 3.85 0.30 2.63 0.19 3.40 0.44 310 N/A
ECOSAR Estimate
Tetraconazole 1.47 0.01 2.40 0.10 3.56 0.38 796 Major Degradates

FM

- 1, SLM

- 1 1 4.48 0.03 1.62 0.22 11.62 1.20 1.61×10 3

FM

- 5 2 1. 27 ×10 5 16.60 591.63 147.42 4.56 ×10 4 4.26×10 3 6.34 ×10 5

FM

- 4 3 3.69×10 5 174.27 5.07×10 3 1.65×10 3 1.63×10 6 1.43×10 5 5.07×10 6

Mino r Degradates

FM

- 7, SLM

- 3 4 3.57×10 3 2.47 49.73 22.77 146×10 4 1.31×10 3 7.95×10 4
SLM

- 6 5 3.96×10 5 169.42 2.34×10 3 1.61×10 3 1.79×10 6 1.55×10 5 3.40×10 3

FM

- 8, SLM

- 2 6 49.37 0.15 11.78 1.29 147.77 14.61 6.41×10 3

SLM

- 4 7 674.18 1.95 140.99 16.46 2.05×10 3 201.53 9.22×10 4

SLM

- 5 8 104.28 0.53 63.08 4.31 281.86 28.79 2.9 1 ×10 4 * ECOSAR Chemical Class: Triazoles (Non

- fused)

** FW = freshwater and ME = marine/estuarine Major Degradates:

1 FM

- 1, SLM

- 1

-- M14360

- dihydro

- isoquinoline

- triazole (10.48% max in aqueous photolysis at Day 4)

2 FM

- 5

-- Tetrafluoroethoxy

- trizolyl

- isobutanoic acid (11.92% max in aqueous photolysis at Day 30)

3 FM

- 4

-- Hydroxy

- triazoyl

- isobutanoic acid (16.73 % max in aqueous photoly sis at Day 22)
Mino r Degradates:

4 FM

- 7, SLM

- 3 (1,2,4

- Triazole)

-- 4H

- 1,2,4

- triazole (8.01% max in aqueous photolysis at Day 22)

5 SLM

- 6 (1,2,4

- Triazole Acetic Acid)

-- 2

- (1H

- 1,2,4

- triazol

- 1

- yl)acetic acid (4 .89% max in soil photolysis at Day 112)

6 FM

- 8, SLM

- 2

-- 2

- (2,4

- dichlorophenyl

- 3

- (1H

- 1,2,4

- triazol

- 1

- yl)

- 1

- propanol (9.25% max in aqueous photolysis at Day 30)

7 SLM

- 4

-- 2

- (2,4

- dichlorophenyl

- 3

- (1H

- 1,2,4

- triazol

- 1

- yl)

- 1

- propionic acid (8.88% max in soil photolysis at Day 112)

8 SLM

- 5

-- 5

- (2,4

- dichloro phenyl

- 2,2

- difluoro

- 6

-- (1H

- 1,2,4

- triazol

- 1

- yl)

- 3

- oxahexanoic acid (6.07% max in soil photolysis at Day 30)

### 40



## Append ix I V

. SIP (Screening Imbibition Program, v1.0) to Evaluate Potential Importance of Drinking Water Pathways

### 41



## Appendix V. STIR ( S creening T ool for I nhalation R isk, v1.0) to Evaluate Potential Importance of Inhalation Exposure Pathways