2

1. Executive Summary

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 overview of the 

environmental fate, ecological effects, 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 conducting 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 Tetraconazole in Previous 

Assessments

Birds Mammals Terr.

Plants

Terr.

Inverts Fish BCF

Aquatic 

Inverts

Aquatic 

Plants Persistence Degradates of Concern

Yes1 Yes2 Yes3 No No No No Yes4 Yes NA5

“Yes” = Risk concerns or issues were identified or presumed in previous assessments 

1Acute 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: Anaerobic soil metabolism: 4 soil systems

 835.4400: Anaerobic aquatic metabolism: 1 additional sediment-water system

 860.1380: Storage stability in soil and water

 850.7100: ECM/ILV: Environmental chemistry methods and independent 

laboratory validation in soil and water (Parent only)

The following ecotoxicity data gaps were identified for the parent tetraconazole (see 

Section 11b for details): 

 850.1350: Saltwater invertebrate life cycle (TGAI)

 850.1400: Saltwater fish early-life stage (TGAI)

 850.1500: Fresh water fish life cycle (TGAI)

 Non-guideline: Whole sediment invertebrate 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: Honeybee adult chronic oral toxicity (TGAI)

 Non-guideline: Honeybee larval acute and chronic oral toxicity (TGAI)

 Non-Guideline: Residue in pollen 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 advance 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 tetraconazole or their differences in fate or toxicity in the environment.

Many of the labels for agricultural uses 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 be reported 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 

subgroup. The number of applications and the maximum application rate should be 

reported on an annual basis. 

If the labels are not clarified, conservative assumptions, such as: multiple seasons or crop cycles 

may be assumed for some crops when performing the 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]triazole, CAS 112281-77-3) was first registered in August,1993 as a broad spectrum systemic 

fungicide with protective, curative, and eradicative 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, through inhibition of ergosterol biosynthesis in cell 

membranes. 

EFED evaluated the most recent ecological risk assessments for tetraconazole in association with 

the updated toxicity, exposure, and usage information to determine if sufficient data are available 

and if further updates are needed to support registration review. 
4

3. Use Characterization

The current registered uses in agricultural crops including, sugar beets, soybeans, pecans, peanuts, 

grapes and corn. Tetraconazole is formulated as emulsifiable concentrate for broadcast application 

by ground and aerial methods, as well as the chemigation. 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 according 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 Site

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 0.0408 NS1,2 14 0.0817

13-07G. Low growing berry subgroup 0.0408 4 14 0.1633

Corn (field) 0.0903 1 NS2(0.0903)

3

Corn (pop) 0.0894 NS2 7 (0.0897)

3

Peanuts (unspecified) 0.1061 NS4,2 14 0.4246

Pecan 0.1306 NS4,2 14 0.5226

Soybeans (unspecified) 0.0753 NS1,2 15 (0.1509)

3

Sugar beet 0.1021 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 soybeans at 30,000 lbs per year 

on average (USEPA 2014a). Table 2.2 shows the average agricultural annual uses (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 Reporting (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 given 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 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 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 assumed 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 peanuts, pecan and soybeans and 80289-8 for 13-07F 

small fruit vine climbing subgroup, except fuzzy kiwifruit and 13-07G low growing berry 

subgroup. 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 assumed for some 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 beet (USEPA 2004a, DP 302899 and USEPA 2005, DP 313005); 

soybeans, peanuts, sugar beets, pecans, and turf (USEPA 2006a, D331424+); grapes (USEPA 

2008a, D350213+); small fruit vine climbing subgroup 13-07F (except fuzzy kiwifruit), low 

growing berry subgroup 13-07G, and corn (USEPA 2010a, D381443+). Tetraconazole is very 

persistent and has potential to accumulate in soil and water. Previous risk assessment 

demonstrated 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. The most recent assessment conducted on sugar beets (USEPA 

2014b, D416108+) incorporated a pollinator risk assessment framework for terrestrial exposures 

(USEPA 2014c) 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 2014b).

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 (acute 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 Assessments

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 2014d; D417463). In this assessment, EFED 

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 Upper Bound 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 beet2

(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 0.52 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 Act1. 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, chemical, environmental fate, and transport properties of tetraconazole are listed in 

Table 5.1. The vapor pressure (1.0 x 10-6mm Hg) and Henry's Law Constant (3.07 x 10-9atm 

m3/mol) of tetraconazole indicate that the compound is considered relatively non-volatile 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 [14C] residues over 6 days exposure) by day 2 of the depuration period. The 

bioaccumulation factor in whole rainbow trout was 39-42x (MRID 44751320).

Tetraconazole does not have a single predominant route of dissipation. The compound is expected 

to be persistent (laboratory and field half-lives 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 days to 204 days (MRID 45851802). 

Tetraconazole is stable to aerobic soil metabolism with half-lives greater than the experimental 

period tested (100 days, MRID 45851801; 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 stable 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 metabolism (~18% at 100 days) studies. The 

unextractable residues may be included in the half-life calculation as parent tetraconazole based 

on the lines of evidences (USEPA 2014e). In addition, the aerobic aquatic metabolism data show 

that tetraconazole partitioned from the water phase into the sediment phase. CO2 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 sandy 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 did 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 ranged from 128 days 

(Italian sandy loam; MRID 44865404) to 800 days (German silty sand; MRID 44865406) and 

did not show movement below a depth of 8 inches. These 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 accumulate 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 

potential 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 C13H11 N3OCl2F4

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 (KOC) (L/kgOC)

3,200 1 44367006

47023201

Henry’s Law Constant 

(atm-m3/mol) 3.07 x 10-9

calculated2

Octanol/water partition 

coefficient (log Kow) 3.53 44305301

Hydrolysis (t1/2) Stable at pH 5, 7, 9 at 25C

(8402 days at pH7; SFO) 44367002

Direct Aqueous Photolysis 

(t1/2)

215 days (September)

107 days (July)

44367003
9

Parameter Value Source/MRID #

Soil Photolysis

(t1/2)

107 days (silt loam)

63 days (sand)

204 days (loamy sand)

81 days (sandy loam)

44367004

45851802

45851802

45851802

Aerobic Soil Metabolism 

(t1/2)

> 365 days (sandy loam)

> 100 days (sand)

> 100 days (loamy sand)

> 100 days (sandy loam)

44367005

45851801

45851801

45851801

Anaerobic Soil 

Metabolism

(t1/2) 

Data Gap --

Aerobic Aquatic 

Metabolism

(t1/2)

382 days (silty loam)

320 days (sandy sediments)

44751319

Anaerobic Aquatic 

Metabolism

(t1/2)

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 

(DT50)

DT50: (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 plot)

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

photolysis studies. 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 an aqueous photolysis study (MRID 44367003).

6. Receptors

The receptor is the biological entity that is exposed to the stressor. The 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-target 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. Direct application of tetraconazole to streams, lakes, 

and ponds is not permitted by the product label, however, tetraconazole residue may enter the 

aquatic system through spray 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 provides a summary of the aquatic taxonomic groups, and the available endpoints for 

the most sensitive surrogate species tested to characterize the potential acute and chronic 

ecological effects 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 LC50: 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 LC50: ≥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 

promelas)

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 LC50: 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 LC50: >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 LC50: 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 EC50: 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 

submitted

NA NA

Aquatic Plants

Macrophytes Duckweed

(Lemna gibba)

7 days EC50: 0.31 mg a.i./L (nonlisted)

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 EC50: 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 residues are 

expected to be found in the surface soil and on foliage (e.g., short and tall grasses, broadleaf 

weeds), seeds, and insects on the treated agriculture field immediately following aerial or ground 

spraying. In addition, the spray drift, and runoff may result in transport of tetraconazole 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 impingement during spray, inhalation; and 

drinking water sources. 

Table 6.2 provides 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 tetraconazole. 

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 LD50 (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 LD50: 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 LD50: >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: 16 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 LC50: 382 mg a.i./kg diet

NOAEC: <304 mg a.i./kg diet

highly toxic

MRID 44367012

(Acceptable)

Bobwhite quail

(Colinus 

virginianus)

Acute dietary LC50: 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 LD50: >130 μg a.i./bee

MRID 44751322

Contact Acute Honeybee (Acceptable)

(Apis mellifera)

96-hour LD50 = 63 μg a.i./bee

practically non-toxic

Non-guideline4 Honeybee adult 

chronic toxicity 

(No data 

submitted)

NA NA NA

Non-guideline4 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 semifield testing for 

pollinators (No 

data submitted)

NA NA NA

Plants – Seedling Emergence

Monocot Four species 

tested a Single 

application

EC25 >0.1 lbs a.i./A

NOAEC = 0.1 lbs a.i./A MRID 45823209

Dicot Six species (Acceptable)

tested b

EC25 >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

EC25 >0.1 lbs a.i./A

NOAEC = 0.1 lbs a.i./A MRID 45823210

Dicot Six species (Acceptable)

tested b

EC25 >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 aerobic soil, anaerobic soil, and hydrolysis pathways. Several 

degradates were found in aqueous or soil photolysis pathway based on the submitted studies. No

toxicity data were submitted for any of the major degradates. The relative aquatic toxicity is

estimated by an ecological structure activity relationship program (ECOSAR v1.11) for both 

major and minor 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. Other degradates are several order of 

magnitude less toxic than the tetraconazole (Appendix III). The registration review risk 

assessment will only consider the parent tetraconazole because of the parent compound’s

persistence 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 have been reported to the Agency. 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 conducted during incident investigation. EIIS incidents are categorized 

according to the certainty that the incident resulted 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 

pesticides. Incidents listed in this database may also be in the EIIS. In addition to the incidents 

recorded in EIIS and AIMS, additional incidents are reported by registrants to the 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 Incident 

Monitoring System (AIMS), and the aggregate Incident Data System (IDS) were performed on 

4/17/15. 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 for 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, LD50 = 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 LD50 = 1031 mg a.i./kg-bw 

and NOAEL = 750 mg a.i./kg-bw) (Appendix IV Table 1). The model indicated that drinking 

water exposure alone is not a potential concern for mammals (Appendix IV Table 2), but it is a 

potential concern for birds (Appendix IV Table 3). 

STIR was used to calculate an upper bound estimate of tetraconazole exposure via inhalation 

using molecular weight (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 quail, LD50 = 

131 mg a.i./kg-bw), and most sensitive acute oral and inhalation mammalian toxicity endpoints 

(rat, LD50 = 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 potential 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 effects 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 individual 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 address 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 literature 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 only 

because the parent was stable and all major degradates were less toxic with only one 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 endpoints 

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 will include the parent tetraconazole only based 

on the MARC memorandum of the Health Effects Division (USEPA 2000; D264157). The 

assessment will be performed based on EFED’s current guidance using appropriate surface and 

groundwater models. Descriptions of all 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

parent 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 used to calculate risk 

quotients. Any additional information submitted by the registrant or found in the open literature 

prior to conducting the risk assessment will also be considered. 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, terrestrial plants, and wildlife. The 

evaluation of both sources of data can also provide insight into the direct and indirect effects of 

pesticides on biotic communities from loss of species that are sensitive to the chemicals and from 

changes in structure and functional characteristics of the affected communities.

9. Endangered Species Assessments

Consistent with EPA’s responsibility under the Endangered Species Act (ESA), the Agency will 

evaluate risks to federally listed threatened and endangered (listed) species from registered uses of 

pesticides in accordance with the Joint Interim Approaches developed to implement the 

recommendations of the April 2013 National Academy of Sciences (NAS) report, (National 

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 obligations 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 (listed) species from 

pesticides. These Interim Approaches were developed jointly by the agencies in response to the 

NAS recommendations and reflect a common approach to risk assessment shared by the agencies 

as a way of addressing scientific differences between the EPA and the Services. Details of the 

joint Interim Approaches are contained in the November 1, 2013 white paper, Interim Approaches 

for National-Level Pesticide Endangered Species Act Assessments Based on the 

Recommendations of the National Academy of Sciences April 2013 Report.

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 registration 

review. While the agencies continue to develop a common method for ESA analysis, the planned 

risk assessment for the registration 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 the scientific 

methods being developed by the agencies have been fully vetted. Once the agencies have fully 

developed and implemented the scientific methods necessary to complete risk assessments for 

endangered and threatened (listed) species and their designated 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

Tetraconazole may have adverse effects on the endocrine system based on the results 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 

(EPISuite 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 2010a, 

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 11.1. 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 metabolism 

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 has 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 is 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

Foreign soils; exaggerated rate of 

parent compound

Data are considered as adequate.

835.6100 Terrestrial Field 

Dissipation

44865404

44865405

44865406

Supplemental

Supplemental

Supplemental

No Foreign 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 

ECM/ILV – Water submitted together in one package -- -- Yes

850.1730 Bioaccumulation in Fish

(BCF)

44751320 Supplemental No --
20

b. Ecological Effects

Table 11.2 and Table 11.3 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 needed 

to support risk assessment. Rationales for non-guideline data that are being recommended are

presented below the tables.

Table 11.2. Aquatic Ecological Effects Data for Tetraconazole and Remaining Data Gaps

OCSPP

Guideline Description MRID Classifications Data Gap Comments

850.1010 Freshwater invertebrate 

acute toxicity

44367018

Water flea 

Daphnia 

magna

Supplemental No

1 No chronic data are available 

for saltwater invertebrates. The 

data are required under 40 CFR 

158 because tetraconazole is 

mobile and stable in water 

(half-life ≥ 320 days. 

2No chronic data are available 

for saltwater fish. The data are 

conditionally required under 40 

CFR 158. Study is 

recommended due to 

tetraconazole persistence. 

3Data for freshwater fish life 

cycle are recommended

because of tetraconazole’s

persistence. In addition, lines 

of evidence show that avian 

hatchling 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 Yes1

(TGAI)*

850.1400 Fish early-life stage 

(Freshwater)

45823208

Fathead 

minnow 

Pimephales 

promelas

Supplemental No

Fish early-life stage 

(Saltwater)

None N/A Yes2

(TGAI)
21

OCSPP

Guideline Description MRID Classifications Data Gap Comments

850.1500 Fish life cycle 

(Freshwater fish)

None N/A Yes3tetraconazole may affect fish 

hatching survival as well.

4Testing 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. 

5Testing is recommended for 

four species, (-a freshwater 

green algae, a cyanobacterium, 

a freshwater diatom and an 

estuarine/marine diatom) to 

support the risk assessment for 

non-vascular plant species.

**NonguidelineWhole sediment –

chronic freshwater 

invertebrates

None N/A Yes4

(TGAI)

Whole sediment –

chronic Saltwater 

invertebrates

None N/A Yes4

(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 Yes5

(TGAI)

850.4550 Cyanobacteria None N/A Yes5

(TGAI)

*TGAI = technical grade active ingredient

**For a non-guideline study, 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 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 Justifications

850.2100 Avian oral toxicity 44367011

Bobwhite quail

Colinus 

virginianus

Acceptable No

1Avian 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 Yes1

(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 Justifications

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 2Honeybee adult chronic 

toxicity data are not available. 

3Acute 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. 

4Additional data may be 

requested at a later date 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). 

**Nonguideline 

(OECD 

213)

Honeybee adult acute 

oral toxicity

44751322

Honeybee

Apis mellifera

Acceptable No

Nonguideline4Honeybee adult chronic 

toxicity 

None N/A Yes2

(TGAI)

Nonguideline4Honeybee larval acute 

and chronic toxicity 

None N/A Yes3

(TGAI)

NonguidelineResidues in pollen and 

nectar

None N/A Yes4

(TEP)*

850.3040 Field or semi-field 

testing for pollinators

None N/A Yes4

(TEP)

850.4100 Seedling Emergence 

and Seedling Growth

45823209 Acceptable Yes5

(TEP)

5Additional 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 Yes5

(TEP)

*TEP = 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 the 

birds, honeybees and plants. Alternatively, if there are no data for any of the triazoles, risks of concern will be presumed.
23

Additional justification for tetraconazole non-guideline data requests:

Study Title: Tier I - Honeybee Adult Chronic Oral Toxicity Study;

Rationale for Requiring the Data

No data have been submitted on the chronic toxicity of tetraconazole to adult honeybees. A 

study is needed to determine the chronic toxicity of the compound to adult honeybees, 

including mortality and sub-lethal effects. This study is part of EFED’s current screeninglevel process for determining 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, 2014c). 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 decisionmaking?

The 10-day toxicity study with young adult bees provides no-observed adverse effect level 

(NOAEL) and lowest-observed adverse effect level (LOAEL) for assessing 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 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 potential 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 performed 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.

Study 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) directly by in-hive nurse bees. EPA guidance (USEPA 2014c) 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 acute and chronic effects to larval bees. 

Practical Utility of the Data

How will the data be used?

The 21-day larval toxicity study1under 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 2372as well as the 21-day repeat dose 

chronic toxicity study to address both acute 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 brood. A protocol for the 21-day larval 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 decision-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 evidence 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 potential 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 performed 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.oecdilibrary.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 bees 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 foliar 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 guidance 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 individual adult bees and larvae. If 

screening-level assessment indicates potential chronic risks to individual bees, then highertier, 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

Chronic sediment toxicity test for the freshwater invertebrate midge (Chironomus riparius)

has 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, benthic 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, additional test with two freshwater species Hyalella Azteca and Chironomus 

tentans, and four saltwater species Ampelisea abdita, Eohaustorius estuaries, Rhepoxynius 

abronius 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 flexibility the Agency and 
26

registrants have in coming into compliance with the Endangered Species Act, and could result 

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. 47pp. 

USEPA. 2004b. Tier II Drinking Water Assessment for the Use of Tetraconazole on Sugar beets. 

DP Barcode: 302899. 11pp.

USEPA. 2004c. Revised Tier II Drinking 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. 2005. Environmental Fate and Effects Division Risk Assessment for the Section 3 

Registration of Tetraconazole. –New Chemical. DP Barcode: 313005. 129pp.

USEPA. 2006a. Environmental Fate and Effects Division Risk Assessment for the Section 3 New 

Use Registration of Tetraconazole. DP Barcodes: 331424, 321742, 323683, 331686, 

321632, 322229, 325324, and 328065. 339pp.

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. 2008a. Environmental Fate and Effects Division Risk Assessment for the Section 3 New 

Use Registration of Tetraconazole. DP Barcode: D350213. 118pp.

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. 2010a. 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. 78pp.
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 Screening Level Usage Analysis (SLUA). Biological and 

Economic Analysis Division, Office of Pesticide Programs, United States Environmental 

Protection Agency. 

USEPA. 2014b. Ecological Risk Assessment for Tetraconazole in Response to Eminent VP 

Label Amendment 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 Agency. 

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)-UTriazole) 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 

Sunlight): 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. Unpublished 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 Ricerca 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. 

44751319 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 14)-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 prepared 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 Column Leaching After 

Ageing (Under Sunlight) of ((Carbon 14)-UTriazole)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 California 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 Agricultural 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 

prepared 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.

46890601 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 Reference

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. (1997) 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: Lab 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 study 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 Huntingdon 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 by 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 of 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: Acute 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) 

Tetraconazole: 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} 

45823208 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 850.1400} 

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 prepared 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 

Project 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 

Revision 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 Lemna 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 Toxicity (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. (1997) 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 crop 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)

0.0408 NS NS Broadcast

Chemigation

Corn (POP)

(Reg # 10163-332, 

80289-7, 66330-422)

0.0903 NS 0.0903

Broadcast

Corn (Field) Chemigation

(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) 0.1509

Soybeans

(Reg # 7969-361) NDC2 2 NS Broadcast

Soybeans

(Reg # 66330-422) NS 2 NS BroadcastChemigation

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: C13H11 N3OCl2F4

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: C2H3N3

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: C4H5N3O2

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-isoquinolinetriazole

Chemical Formula:

C13H10Cl1F4N3O

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-(1H1,2,4-triazol-1-yl)-1-propanol

Chemical Formula: C11H11Cl2N3O

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-trizolylisobutanoic acid

Chemical Formula: C8H11F4N3O3

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: C6H11N3O3

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-(1H1,2,4-triazol-1-yl)-1-propionic 

acid

Chemical Formula: C11H11Cl2N3O2

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:

C13H13Cl2F2N3O3

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 

LC50

(mg/L)

FW fish 

chronic 

NOAEC

(mg/L)1

FW**

invertebrate 

48-hr acute 

EC50

(mg/L)

FW 

invertebrate 

chronic 

NOAEC

(mg/L)1

ME fish 96-

hr acute 

LC50

(mg/L)

ME**

invertebrate 

96-hr acute 

LC50

(mg/L)

Vascular 

plant 7-

day EC50

(μg/L)

Nonvascular 

plant 96-

hr EC50

(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 1.61×103

FM-5

2 1.27×105 16.60 591.63 147.42 4.56×104 4.26×103 6.34×105

FM-4

3 3.69×105 174.27 5.07×103 1.65×103 1.63×106 1.43×105 5.07×106

Minor Degradates

FM-7, SLM-3

4 3.57×103 2.47 49.73 22.77 146×104 1.31×103 7.95×104

SLM-6

5 3.96×105 169.42 2.34×103 1.61×103 1.79×106 1.55×105 3.40×103

FM-8, SLM-2

6 49.37 0.15 11.78 1.29 147.77 14.61 6.41×103

SLM-4

7 674.18 1.95 140.99 16.46 2.05×103 201.53 9.22×104

SLM-5

8 104.28 0.53 63.08 4.31 281.86 28.79 2.91×104

* 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 photolysis at Day 22)

Minor 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-dichlorophenyl-2,2-difluoro-6--(1H-1,2,4-triazol-1-yl)-3-oxahexanoic acid (6.07% max in soil photolysis at Day 30)
40

Appendix IV. SIP (Screening Imbibition Program, v1.0) to Evaluate 

Potential Importance of Drinking Water Pathways

Table 1. Inputs

Parameter Value

Chemical name Tetraconazole

Solubility (in water at 25oC; mg/L) 156

Mammalian LD50 (mg/kg-bw) 1031

Mammalian test species laboratory rat

Body weight (g) of "other" mammalian species

Mammalian NOAEL (mg/kg-bw) 750

Mammalian test species laboratory rat

Body weight (g) of "other" mammalian species

Avian LD50 (mg/kg-bw) 382

Avian test species mallard duck

Body weight (g) of "other" avian species 131

Mineau scaling factor 1.15

Mallard NOAEC (mg/kg-diet) 304

Bobwhite quail NOAEC (mg/kg-diet) 25

NOAEC (mg/kg-diet) for other bird species

Body weight (g) of other avian species

NOAEC (mg/kg-diet) for 2nd other bird species

Body weight (g) of 2nd other avian species

Table 2. Mammalian Results

Parameter Acute Chronic

Upper bound exposure (mg/kg-bw) 26.8320 26.8320

Adjusted toxicity value (mg/kg-bw) 793.0045 576.8704

Ratio of exposure to toxicity 0.0338 0.0465

Conclusion*

Drinking water exposure 

alone is NOT a potential 

concern for mammals

Drinking water exposure 

alone is NOT a potential 

concern for mammals

Table 3. Avian Results

Parameter Acute Chronic

Upper bound exposure (mg/kg-bw) 126.3600 126.3600

Adjusted toxicity value (mg/kg-bw) 198.3441 2.6575

Ratio of exposure to acute toxicity 0.6371 47.5492

Conclusion*

Exposure through drinking 

water alone is a potential 

concern for birds

Exposure through drinking 

water alone is a potential 

concern for birds

*Conclusion is for drinking water exposure alone. This does not combine all routes of exposure. Therefore, 

when aggregated with other routes (i.e., diet, inhalation, dermal), pesticide exposure through drinking water 

may contribute to a total exposure that has potential for effects to non-target animals.
41

Appendix V. STIR (Screening Tool for Inhalation Risk, v1.0) to 

Evaluate Potential Importance of Inhalation Exposure Pathways

Input

Application and Chemical Information

Enter Chemical Name Tetraconazole

Enter Chemical Use Pecan

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

If Spray What Type (enter ground or air) air

Enter Chemical Molecular Weight (g/mole) 372.1

Enter Chemical Vapor Pressure (mmHg) 9.90E-07

Enter Application Rate (lb a.i./acre) 0.5226

Toxicity Properties

Bird

Enter Lowest Bird Oral LD50 (mg/kg bw) 131

Enter Mineau Scaling Factor 1.15

Enter Tested Bird Weight (kg) 0.178

Mammal

Enter Lowest Rat Oral LD50 (mg/kg bw) 1031

Enter Lowest Rat Inhalation LC50 (mg/L) 40.6

Duration of Rat Inhalation Study (hrs) 4

Enter Rat Weight (kg) 0.35

Output

Results Avian (0.020 kg )

Maximum Vapor Concentration in Air at Saturation (mg/m3) 1.98E-02

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 2.49E-03

Adjusted Inhalation LD50 2.88E+01

Ratio of Vapor Dose to Adjusted Inhalation LD50 8.66E-05 Exposure not Likely Significant

Maximum Post-treatment Spray Inhalation Dose (mg/kg) 5.02E-02

Ratio of Droplet Inhalation Dose to Adjusted Inhalation LD50 1.75E-03 Exposure not Likely Significant

Results Mammalian (0.015 kg )

Maximum Vapor Concentration in Air at Saturation (mg/m3) 1.98E-02

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 3.13E-03

Adjusted Inhalation LD50 2.42E+03

Ratio of Vapor Dose to Adjusted Inhalation LD50 1.30E-06 Exposure not Likely Significant

Maximum Post-treatment Spray Inhalation Dose (mg/kg) 6.31E-02

Ratio of Droplet Inhalation Dose to Adjusted Inhalation LD50 2.61E-05 Exposure not Likely Significant

**NOTE**: When entering values, press the "Enter" 

in order to update linked cells.