UNITED STATES ENVIRONMENTAL PROTECTION 

AGENCY 

MEMORANDUM 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

PC Code: 125618 

DP Barcode: 0428127 

Date: December 9, 2015 

SUBJECT: EFED Registration Review Problem Fomrnlation for Ipconazole 

FROM: 

TO: 

REVIEWED BY: 

THROUGH: 

. t>/10/15 

Hannah Yingling, Biologist~~~~ Mohammed Ruhman, Ph.D., Senior Agronomi~ \. 

Environmental Risk Branch 5 ~ · IJ../fo/15 

Environmental Fate and Effects Division (7507P) 

Brittany Pruitt, Chemical Review Manager 

Tracy Perry, Team Leader 

Risk Management and Implementation Branch 3 

Pesticide Re-Evaluation Division (7508P) 

Allen Vaughan, Entomologist 

Gabe Rothman, Environmental Scientist 

Environmental Risk Branch 5 

Environmental Fate and Effects Division (7507P) 

Mah Shamim, Branch Chief 

Environmental Risk Branch 5 

Environmental Fate and Effects Division (7507P) 

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

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

water assessments to be conducted as part of the registration review of ipconazole. 
2

OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION

UNITED STATES ENVIRONMENTAL PROTECTION

AGENCY

EFED Registration Review Problem Formulation for Ipconazole

Ipconazole: 2-[(4-Chlorophenyl) methyl]-5-(1 -methylethyl)-1-(1 H- 1, 2, 4triazol-1-y1metyl)

cyclopentanol;

CAS No.: 125225-28-7 and PC code: 125618

Date: September 30, 2015

Hannah Yingling, Biologist

Mohammed Ruhman, Ph.D., Senior Agronomist

Environmental Risk Branch 5

Environmental Fate and Effects Division (7507P)
3

Table of Contents

1. Executive summary................................................................................................................. 4

A. Environmental Fate Data Gaps ..........................................................................................4

B. Ecological Effects Data Gaps.............................................................................................4

C. Uncertainties.......................................................................................................................5

2. Introduction............................................................................................................................. 6

3. Use Characterization............................................................................................................... 6

4. Conclusions for Previous Risk Assessments........................................................................ 11

A. Drinking Water Exposure Assessments...........................................................................12

B. Clean Water Act Programs...............................................................................................13

5. Environmental Fate and Transport........................................................................................ 14

6. Receptors............................................................................................................................... 18

A. Effects to Aquatic Organisms ..........................................................................................19

B. Effects to Terrestrial Organisms ......................................................................................20

C. Ecological Incidents.............................................................................................................. 22

7. Exposure Pathways of Concern ............................................................................................ 22

8. Analysis Plan ........................................................................................................................ 23

A. Stressors of Concern.........................................................................................................23

B. Measures of Exposure ......................................................................................................23

C. Available Monitoring Data...............................................................................................24

D. Measures of Effect ...........................................................................................................24

9. Endangered Species Assessments......................................................................................... 24

10. Endocrine Disruptor Screening Program.............................................................................. 25

11. Preliminary Identification of Data Gaps............................................................................... 25

A. Environmental Fate ..........................................................................................................25

B. Ecological Effects ............................................................................................................26

12. References............................................................................................................................. 33

Appendix A. Study Justification Tables .......................................Error! Bookmark not defined.

Appendix B. Example of SIP Input .............................................................................................. 38

Appendix C. Example of STIR Output......................................................................................... 40

Appendix D. Full Study Details for all Toxicity Studies.............................................................. 41

Appendix E. Comparison of Conazole Aquatic Toxicity Endpoints in ppm............................... 48
4

1. Executive summary

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

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

assessments to be conducted as part of the registration review of the seed treatment, ipconazole. 

The problem formulation describes the methods planned to be used during the completion of 

drinking water and ecological risk assessments in support of registration review for the systemic 

fungicide ipconazole. This document provides an overview of the environmental fate, ecological 

effects, potential risks associated with its uses and the uncertainties which currently exist relevant 

to the risk assessment of this chemical. This document also identifies additional studies that 

would be beneficial to conduct before executing the future registration review ecological risk 

assessment. 

A. Environmental Fate Data Gaps

The fate database for ipconazole is partially complete with the exception of the following studies,

which are requested:

(1) One aerobic soil study (OCSPP 835.4100) for one soil obtained from areas where the 

pesticide is used. The study is requested to be conducted using the same isomer mixture 

present in the active ingredient and track both isomers. This is in addition to identifying 

if isomers are biologically active and if they differ in toxicity;

(2) One adsorption/desorption study (OCSPP 835.6100) with one soil with an isomer 

mixture similar to the active ingredient of the pesticide (Note: This study is not required 

if the registrant confirms that previous studies were conducted with an isomer mixture 

similar to that stated for the active ingredient of the pesticide);

(3) An anaerobic water/sediment study (OCSPP 835.4400) for two systems; and

(4) ECMs and associated ILVs (OCSPP 850.6100) for soil/sediment and water;

(5) Fish bio-concentration: No study was submitted for this chemical. A fish bioconcentration study is requested due to the relatively high Kow of the isomer mixture 

(16,218) of ipconazole.

B. Ecological Effects Data Gaps

The ecological database for ipconazole has a number of outstanding data gaps as follows:

(1) Acute toxicity using Fathead minnow or using Rainbow Trout (850.1400) or Bluegill 

sunfish (850.1075)

(2) Chronic freshwater Invertebrate using Daphnia magna (850.1300)

(3) Acute toxicity using estuarine/marine fish (850.1075)

(4) Chronic toxicity using estuarine/marine fish (850.1400)

(5) Acute toxicity using estuarine/marine invertebrate (850.1035/850.1025)
5

(6) Mysid Chronic (850.1350)

(7) Aquatic vascular plant toxicity (850.4400)

(8) Aquatic nonvascular plant toxicity (850.4550/850.4500)

(9) Whole sediment toxicity testing (850.1735)

(10) Avian acute oral toxicity using a passerine species (850.2100)

(11) Acute toxicity to terrestrial vascular plants: Seedling Emergence study (850.4100)

(12) Honeybee acute contact study (850.3020)

(13) Acute oral toxicity to adult honeybees (Non-guideline; OECD 213)

(14) Acute oral toxicity to larval honeybees (Non-guideline; OECD 237)

(15) Chronic oral toxicity to adult honey bees (Non-guideline)

(16) Chronic oral toxicity to larval honey bees (Non-guideline)

(17) Pollinator feeding/semi-field study - The need for these studies is contingent upon the 

results of lower tier bee studies (Non-guideline)

(18) Pollen and nectar residue studies – The need for these studies is contingent upon the 

results of lower tier bee studies (Non-guideline)

(19) Field testing for pollinators – The need for field testing is contingent upon the results of 

lower tier bee studies (850.3040)

C. Uncertainties

The active ingredient ipconazole exists as a complex stereoisomer. As described by the 

registrant, it appears that the technical grade active ingredient of ipconazole exists as a 9:1 

mixture of two stereoisomers cis, cis ipconazole: cis, trans ipconazole. However, the molecular 

structure indicates that there are 3 chiral centers, and as such there are 8 possible isomers (e.g., 

enantiomers) in the mixture. Therefore, the two isomers as currently described in the technical 

grade mixture can be more explicitly described as R- and S- isomers since the molecular structure 

indicates this possibility. Furthermore, the existing cis- and trans- distinctions of the mixture 

currently identified may be referenced to the different R- and S- configurations to establish the 

similarities or differences in the nature of these isomers from the overall mixture with the single 

active ingredient compound (see information in the next paragraph). More clarity is needed on 

the identification of the test substance since existing fate studies are referenced specific to the 

compound’s cis and trans described forms.

The registrant is requested to:

(1) Confirm/modify the following statements: The registrant submitted fate studies refer to 

the technical grade ipconazole as a 9:1 mixture of two stereoisomers cis, cis: cis, trans. In 

this document, EFED used the same terminology in order to be consistent with the 

registrant data. However, it should be noted that the molecule has a complex 

stereochemistry, with 3 chiral centers and 8 possible isomers, and the two isomers present 

in the technical grade mixture should probably more appropriately be described as R- and 

S- isomers;

(2) Confirm/modify the physical properties listed for the isomers in Table 6 of the 

environmental fate and transport section with documentation supporting the information 

provided;
6

(3) Designate as to which of the isomers is the biologically active compound or whether they 

are both biologically active; and

(4) Clarify the following uncertainty associated with already submitted environmental fate 

studies (all submitted studies):

“Studies were conducted using an isomer mixture similar to that stated for the active ingredient of 

the pesticide (9:1)” 

(5) Clarify the mixture of stereoisomers in the technical product used in each of the 

ecotoxicity studies.

Therefore, the registrant is requested to present comparative data on degradation rates and 

sorption affinity of ipconazole of the varied isomer components of the technical grade material 

used in formulating the pesticide. In case data and clarifications are not responded to, EFED will 

use conservative assumptions such as assuming stability and/or multiplying half-life with a factor 

of 3 for non-submitted studies.

2. Introduction

Ipconazole is a systemic and contact broad-spectrum seed treatment fungicide. It is expected to be 

widely used in many parts of the USA as it is registered for seed treatment in many crops. The 

crops include buckwheat, canola rape & mustard, conifers, corn (field, pop & sweet), millet, 

ornamental flowers, peanuts, sorghum, soybeans, sunflower, turf grass, some cereal grains 

(wheat, barley, oats, rye & triticale) and crop groups including: beans and peas, vegetables 

(Brassica “cole” leafy, cucurbits, leafy except Brassica, legumes, and some root & tuber) and 

forage and silage of corn, millet, rye, triticale, sorghum, wheat, barley and oats.

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

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

if further updates are needed to support future Registration Review. Recent ecological risk 

assessments for ipconazole included: the 2007 Environmental and Ecological Risk Assessment 

for Use of Ipconazole as Seed Treatment for Small Grain Cereal Crops (except rice) soybean, 

peanut and dry-shelled peas (D337783). In addition, EFED considered the latest Agency science 

policies and risk assessment methodologies.

3. Use Characterization

There are 12 registered end-use products for ipconazole1 formulated as liquid and liquid 

suspension. The chemical is solely used as a seed treatment for many crop and crop groups 

(Table 1a, b and c). Ipconazole is a systemic fungicide formulated alone or with other pesticide 

active ingredients including: thiram, metalaxyl, carboxin “systemic fungicides with different 

mode of action” and the insecticides imidacloprid and clothianidin (Table 1a, b and c). A list of 

crops in the crop groups are included in Table 2.

 
7

Table 1a Products and use patterns for ipconazole and its mixtures. The maximum seed rates (lbs. 

ipconazole/100 lbs. of seeds are included; All of these products for Chemtura Company)

Product Name

RANCONA®

3.8 FS Apex 1 Ipconazole/Thiram

10/350 FS Pinnacle Summit

EPA Registration Number 400-544 400-546 400-547 400-566 400-570

Label Stamp Date (month-year) Oct-14 Jun-14 Sep-09 Dec-13 Jan-14

% Ipconazole in the a.i 40.700% 0.440% 0.870% 0.434% 0.902%

Other Chemicals in the a.i None None Thiram Metalaxyl Metalaxyl

Maximum Rate: lbs. Ipconazole/100 lbs. Seeds

Crop or Crop Group/ Product 3.8 FS Apex 1 I/T 10/350 FS Pinnacle Summit

Beans and Peas 2.50E-03 No Use 2.49E-03 No Use No Use

Buckwheat 2.50E-03 2.47E-03 2.49E-03 2.51E-03 No Use

Canola Rape 1.00E-02 No Use 2.49E-03 No Use No Use

Conifers 1.00E-02 No Use No Use No Use No Use

corn, field 2.50E-03 2.47E-03 2.49E-03 No Use No Use

Corn, popcorn 2.50E-03 2.47E-03 No Use No Use No Use

corn, sweet 2.50E-03 2.47E-03 2.49E-03 No Use No Use

Cotton 1.00E-02 No Use No Use No Use No Use

Millet 2.50E-03 2.47E-03 2.49E-03 No Use No Use

Mustard 1.00E-02 No Use 2.49E-03 No Use No Use

Ornamental flowers 1.00E-02 No Use 2.49E-03 No Use No Use

Peanuts 2.50E-03 No Use 2.49E-03 No Use No Use

Rye and Triticale 2.50E-03 2.47E-03 2.49E-03 2.51E-03 2.50E-03

Sorghum 5.01E-03 2.47E-03 5.05E-03 2.51E-03 No Use

Soybeans 2.50E-03 No Use 2.49E-03 No Use No Use

Sunflower 2.50E-03 No Use 2.49E-03 No Use No Use

Turf grass 2.50E-03 No Use 2.49E-03 No Use No Use

Vegetables: Brassica (Cole) 

leafy 1.00E-02 No Use No Use No Use No Use

Vegetables: Cucurbits 1.00E-02 No Use No Use No Use No Use

Vegetables: Leafy except 

Brassica 1.00E-02 No Use No Use No Use No Use

Vegetables: Legume 2.50E-03 No Use No Use No Use No Use

Vegetables: Root 1.00E-02 No Use No Use No Use No Use

Wheat, Barley and Oats 2.50E-03 2.47E-03 2.49E-03 2.51E-03 2.50E-03

1

For Apex: Uses include forage and silage for the following crops: corn (field/sweet), sorghum, wheat, barley and oats

1 As per the Pesticide Product Label System, the following labels are cancelled by Bayer in 2014-20015: Ipconazole 

Metalaxyl MD (S) (EPA Registration No. 7501-211); Vortex 2000 (EPA Registration No. 264-1076) and Three-Way 

Vap (EPA Registration No. 264-1079): URL: http://iaspub.epa.gov/apex/pesticides/f?p=PPLS:1

Table 1b Products and use patterns for ipconazole and its mixtures. The maximum seed rates (lbs. ipconazole/100 

lbs. of seeds are included.

Company Name Chemtura
8

Product Name RANCONA®

Xxtra Crest WR Crest 1 V RS Xxtra Pro

EPA Registration Number 400-571 400-573 400-574 400-581 400-591

Label Stamp Date (month-year) May-12 Sep-13 Nov-13 Nov-13 Sep-11

Stamped Registration Status Accepted Accepted Notification Notification Accepted

% Ipconazole in the a.i 1.029% 0.439% 0.421% 0.727% 1.029%

Other Chemicals in the a.i Metalaxyl Metalaxyl+ Imidacloprid Carboxin Metalaxyl

Maximum Rate: lbs. Ipconazole/100 lbs. Seeds

Crop or Crop Group/ Product Xxtra Crest WR Crest 1 V RS Xxtra Pro

Beans and Peas 2.50E-03 No Use No Use No Use 2.50E-03

Buckwheat No Use No Use No Use No Use No Use

Canola Rape No Use No Use No Use 7.50E-03 No Use

Conifers No Use No Use No Use No Use No Use

Corn (field, pop and sweet) No Use No Use No Use No Use No Use

Cotton No Use No Use No Use No Use No Use

Millet No Use No Use No Use No Use No Use

Mustard No Use No Use No Use No Use No Use

Ornamental flowers No Use No Use No Use No Use No Use

Peanuts No Use No Use No Use No Use No Use

Rye and Triticale No Use 2.51E-03 2.50E-03 No Use No Use

Sorghum No Use No Use No Use No Use No Use

Soybeans 2.50E-03 No Use No Use No Use 2.50E-03

Sunflower No Use No Use No Use No Use No Use

Turf grass No Use No Use No Use No Use No Use

Vegetables: Brassica (Cole) leafy No Use No Use No Use No Use No Use

Vegetables: Cucurbits No Use No Use No Use No Use No Use

Vegetables: Leafy except Brassica No Use No Use No Use No Use No Use

Vegetables: Legume No Use No Use No Use No Use No Use

Vegetables: Root No Use No Use No Use No Use No Use

Wheat, Barley and Oats No Use 2.51E-03 2.50E-03 No Use No Use

1 For Crest: Uses include forage and silage for the following crops: corn (field/sweet), sorghum, wheat, barley 

and oats

Table 1c. Products and use patterns for ipconazole and its mixtures. The maximum seed rates (lbs. ipconazole/100 

lbs. of seeds are included.

Company Name Chemtura Bayer 1 Valent

Product Name RANCONA® 

CTS VORTEX® 2 INOVATETM INOVATETM Neutral

EPA Registration Number 400-592 264-988 59639-176 59639-187

Label Stamp Date (month-year) Jun-14 Nov-08 Aug-12 Jan-12

Stamped Registration Status Accepted

Accepted

w/comments Notification Accepted
9

% Ipconazole in the a.i 2.420% 40.700% 0.720% 0.720%

Other Chemicals in the a.i Metalaxyl None

Clothianidin

& Metalaxyl

Clothianidin

& Metalaxyl

Maximum Rate: lbs. Ipconazole/100 lbs. Seeds

Crop or Crop Group/ Product RANCONA® 

CTS VORTEX® 2 INOVATETM INOVATETM Neutral

Beans and Peas 2.50E-03 No Use No Use No Use

Buckwheat No Use No Use No Use No Use

Canola Rape No Use 1.00E-02 No Use No Use

Conifers No Use 1.00E-02 No Use No Use

corn, field No Use 2.50E-03 No Use No Use

Corn, popcorn No Use 2.50E-03 No Use No Use

corn, sweet No Use 2.50E-03 No Use No Use

Cotton No Use 1.00E-02 No Use No Use

Millet No Use No Use No Use No Use

Mustard No Use 1.00E-02 No Use No Use

Ornamental flowers No Use 1.00E-02 No Use No Use

Peanuts No Use 2.50E-03 No Use No Use

Rye and Triticale 2.50E-03 No Use No Use No Use

Sorghum 2.50E-03 5.01E-03 No Use No Use

Soybeans 2.50E-03 No Use 2.50E-03 2.50E-03

Sunflower No Use 2.50E-03 No Use No Use

Turf grass No Use 2.50E-03 No Use No Use

Vegetables: Brassica (Cole) 

leafy No Use 1.00E-02 No Use No Use

Vegetables: Cucurbits No Use 1.00E-02 No Use No Use

Vegetables: Leafy except 

Brassica No Use 1.00E-02 No Use No Use

Vegetables: Legume No Use No Use No Use No Use

Vegetables: Root No Use 1.00E-02 No Use No Use

Wheat, Barley and Oats 2.50E-03 No Use No Use No Use

1 For Bayer: The following products are cancelled in July, 2014: Registration No.’s 7501-211 and 264-1079; and Registration 

No. 264-1076 (March, 2015); Per the pesticide product label system; URL: http://iaspub.epa.gov/apex/pesticides/f?p=PPLS:1 2 For VORTEX: Uses include forage and silage for the following crops: corn (field/sweet), sorghum, wheat, barley and oats

Use patterns for crop groups are listed in Table 2 include: beans and peas and vegetable crops 

(root/tuber, brassica, leafy, cucurbits and legumes).

Table 2 Crops within use patterns for ipconazole and its mixtures

Crop Group Crops

Beans & Peas

beans (lupin, field, kidney, lima, navy, pinto, tepary, moth, mung, rice, fava, urd, 

adzuki, lablab); peas (blackeyed, field, cow, croder, crowder, southern, chick, 

pigeon); lentil and guar

Vegetables: 

Root/Tuber

Beet (sugar and garden), burdock (edible), carrot, celeriac, chervil (turnip-rooted), 

chicory (roots), chufa, dandelion (roots), ginseng, parsley (turnip-rooted), parsnip, 
10

Table 2 Crops within use patterns for ipconazole and its mixtures

Crop Group Crops

radish, radish (oriental), rutabaga, salsify, salsify (black), salsify (Spanish), skirret, 

turnip and yam bean

Vegetables: 

Brassica (Cole) 

Leafy Group

Broccoli, broccoli (Chinese), broccoli (raab), Brussels sprouts, cabbage (including 

Chinese bok choy, Chinese napa, and Chinese mustard), cauliflower, cavalo broccolo, 

collards, kale, kohlrabi, mizuna, mustard greens, mustard spinach, and rape greens.

Vegetables: Leafy, 

except Brassica

Amaranth (leafy, Chinese spinach, tampala), arugula, cardoon, celery (including 

Chinese), celtuce, chervil, chrysanthemum (edible-leaved and garland), corn salad; 

cress (garden and upland), dandelion, dock, endive, fennel (Florence, finochio), 

lettuce (head and leaf), orach, parsley, purslane (garden and winter), radicchio, 

rhubarb, spinach, spinach (New Zealand), spinach (vine), and Swiss chard.

Vegetables: 

Cucurbits

Chayote, Chinese waxgourd, citron melon, cucumber, gherkin, gourd edible (includes 

hyotan, cucuzza, hechima, Chinese okra),

Momordica, all muskmelon, pumpkin, squash and watermelon.

Vegetables: 

Legumes 

(Succulent or 

Dried)

Includes all crops listed, above for beans and peas in addition to: beans (runner, 

snap, wax, asparagus, catjang, Chinese long, yardlong, jack, sword) and peas (dwarf, 

edible-podded, English, garden, green, snow, sugar snap)

Table 3 contains a summary of the maximum rate per 100 lbs. of seeds. These values are the 

maximum label rates among the 14 formulations. These rates are the rates to be used for future 

modeling for both ecological and drinking water exposure concentrations.

Table 3 Maximum application rates for crops and crop groups in lbs. a.i/100 lbs. seeds

Crop Max. Rate Crop Group Max. Rate

Buckwheat 2.51E-03 Beans and Peas 2.50E-03

Canola Rape & Mustard 1.00E-02

Vegetables: Brassica (Cole) 

leafy 1.00E-02

Conifers 1.00E-02 Vegetables: Cucurbits 1.00E-02

Corn (field, pop and sweet) & 

Millet 2.50E-03

Vegetables: Leafy except 

Brassica 1.00E-02

Cotton 1.00E-02

Vegetables: Legume 2.50E-03

Vegetables: Root & Tuber 1.00E-02

Ornamental flowers 1.00E-02 Forage and Silage:

Peanuts 2.50E-03 (1) Corn (field & sweet) 2.50E-03

Sorghum 5.05E-03 (2) Millet, Rye & Triticale 2.47E-03

Soybeans 2.50E-03

Sunflower 2.50E-03 (3) Sorghum 5.01E-03

Turf grass 2.50E-03

Wheat, Barley, Oats, Rye & (4) Wheat, Barley and Oats 2.51E-03

Triticale 2.51E-03

Ecological and drinking water maximum exposure concentrations for surface water are expected 

to depend mainly on chosen representative scenarios, the maximum label rate (lbs. of ipconazole 
11

a.i/acre), and the minimum seeding depth. The maximum label rate in lbs. /acre will depend on 

the maximum amount of seeds needed to seed an acre of the crop in question (seeding rate). 

Seeding depth is also dependent mainly on the crop (can be obtained) and other factors that are

difficult to determine such as the depth where moisture is available for seed growth (seeding 

depth). The maximum seeding rate will be obtained from BEAD report 2 while minimum seeding 

depth will be obtained from the literature. The following steps will be taken for surface water 

modeling:

(1) Lbs. a.i./acre rates will be calculated for ALL crops including crops that are within 

All groups;

(2) A list for all the crops containing maximum lbs. a.i./acre label rates and minimum 

seeding depths will be established along with representative scenarios. From the list, 

representative scenarios will be simulated for each entry in the list to calculate EECs 

in aquatic environments; noting that a scenario may be used in simulations at different 

depths and/or different rates.

The above mentioned approach for preparing data for modeling including scenarios choice are 

detailed elsewhere3

. This approach may need to be slightly modified in consideration of the use 

patterns at that time. It is noted that potato, sweet potato, and Bermuda grass are not among the 

crops registered for this chemical (registrant Letter dated October 11, 2004).

The registrant is requested to review the information presented above for labeled uses of this 

chemical and inform EFED of any discrepancy. Finally, it is noted that future modeling assumes 

that “Crops are to be seeded at appropriate depths and No broadcast seeding is allowed for treated 

seeds”. The registrant is requested to include this statement on the label for treated seed bags. 

4. Conclusions for Previous Risk Assessments

EFED has conducted ecological risk assessments for Ipconazole that serve as the basis for this 

problem formulation, including the 2007 new use assessment (D337783) on small grain cereal 

crops (except rice), soybean, peanut, and dry-shelled beans and peas. The baseline risk 

assessment for ipconazole suggests that environmental concentrations for aquatic and terrestrial 

animals were low because of its use at very low rates as a seed treatment fungicide. The highest 

previously assesed EECs for ipconazole were 0.05 ppb (rye) for aquatic animals and 25.2 ppm 

(cotton) for terrestrial animals. 

The acute and chronic toxicity values for freshwater fish and invertebrates were in ppm ranges 

and were several orders of magnitude greater than the EECs (which are measured in ppb). 

Therefore, no RQ values exceeded the Agency’s acute risk LOC for listed or non-listed

freshwater fish and aquatic invertebrates. Chronic toxicity data was available for freshwater fish 

 2 J. Becker and S. Ratnayake, 2011. Acres Planted per Day and Seeding Rates of Crops Grown in the United States. 

BEAD report, EPA.

3 Refer to the 2nd drinking water assessment: Drinking Water Exposure Assessment for Ipconazole Use as Seed 

Treatment on Cotton, Peanuts, Soybean, Cereal Grains (except Rice) and Pea and Beans (Dry Shelled); EFED 

Memorandum dated August 22, 2007; DP Barcode: DP339009. 
12

only. Similar to acute RQs, the chronic RQs for fish did not exceed the listed or non-listed 

species’ level of concern.

The most sensitive acute toxicity endpoint for birds (LD50 = 962 ppm) and mammals (LD50 = 468 

ppm) was 38 and 22 times greater than the highest exposure concentration for birds (25.2 ppm) 

and mammals (21.1 ppm). As a result, avian and mammalian acute RQ values did not exceed the 

listed and non-listed species LOC (0.5 and 0.1 respectively.) Chronic RQs, are exceeded for birds 

(cotton only; RQ = 2.1) and mammals (all crops; RQs = 3.0 – 12.1).Chronic exposure to avian 

species and mammals may result in reproductive effects. Effects seen in maternal and 

developmental toxicity have been summarized in Section 6. 

Table 4 Summary of conclusions from previous ecological risk assessments

Birds Mammals Terr 

Plants

Terr 

Inverts Fish BCF Aquatic Inverts

Aquatic 

Plants

Groundwater 

Contamination Persistence Degradates of Concern

Yes1 Yes2 Yes3 Yes4 Yes5 Refer to 6 Yes7 Yes8 Yes9 Yes No10

1 Potential for chronic risk to birds for cotton use; no acute risk; 2 Potential for chronic risk to mammals for cotton use; no acute risk;

3 No data was available for risk conclusion; risk was assumed; 4 No data was available for risk conclusion; risk was assumed;

5 No acute or chronic risk for freshwater fish; No data was available for risk conclusions to estuarine/marine species; risk was 

assumed;

6 No BCF study was submitted. 7 No risk for acute freshwater invertebrates; no chronic data was available for freshwater invertebrates; no acute or chronic data was 

available for risk conclusions for estuarine/marine acute invertebrates; risk was assumed 8 No data was available for risk conclusion; risk was assumed;

9 Ground water was the driver for the drinking water risk assessment mainly due to the high persistence of the parent which appears 

to overcome it expected low mobility (Average Koc= 2,428 Kg L-1); 10 This decision is based on current fate data which indicates parent is applied at low rate, highly persistence and the degradate 1, 2, 4 

triazole (a common degradate of the conazoles4 pesticides) formed at low concentration in one of the soils (Averaged a maximum of 

12% @ 31 days and declined to a ranged from 6-9% between 59 and 365 days). This decision may change upon review of requested 

studies and information.

A. Drinking Water Exposure Assessments

Previously, two Tier I and one Tier II drinking water assessments were developed for this 

chemical. Tier I assessments were based on FIRST (version 1, 2001) for surface water and 

SCIGROW-2 (version 2.3, 2003) for ground water5

. The 1st assessment was based on use as per 

 4 Refer to EFED Memo entitled: 1, 2, 4-Triazole, Triazole Alanine, Triazole Acetic Acid: Drinking Water 

Assessment in Support of Reregistration and Registration Actions for Triazole-derivative Fungicide Compounds. 

Risk Assessment Type: Single Chemical Aggregate (PC Codes: 600074 – 1, 2, 4-Triazole; 600011 – Triazole 

Alanine; 600082 – Triazole Acetic Acid. DP Number: D320682; Dated Feb 28, 2006. 5 1st assessment: Addendum: Tier 1 Drinking Water Concentrations for Seed Treatment Uses of Ipconazole; EFED 

Memorandum dated March 15, 2004; DP Barcode: D289658; and;

2nd assessment: Drinking Water Exposure Assessment for Ipconazole Use as Seed Treatment on Cotton, Peanuts, 

Soybean, Cereal Grains (except Rice) and Pea and Beans (Dry Shelled); EFED Memorandum dated August 22, 2007; 

DP Barcode: DP339009.
13

one label (Vortex) while the 2nd assessment was based on additional new use patterns as per 

additional three labels. In these assessments, the driver for the EDWCs, for surface and ground 

water, was seed treatment on potato which was not intended to be included in the labels among 

the root & tuber crop group (both potato and sweet potato are not to be included in any label). 

The last drinking water assessment for ipconazole was a Tier II assessment and was conducted in 

July 2013 covering all use patterns at that time (17 labels)6. This assessment was necessary in 

order to (1) cover all current labels, (2) consider changes in some labels, (3) exclude nonregistered use patterns (i.e., potato & sweet potato), and (4) correct use label rates in lbs. a.i/A for 

most of the crops to reflect all current labels and the newly published crop seeding rates by 

BEAD. Modeling for this assessment was conducted using Tier II PRZM/EXAMS with 

EXPRESS shell for surface water exposure and Tier I PRZM-GW for ground water exposure. 

In all of these assessments, the stressor of concern was considered to be parent ipconazole

because no determination was made to include any residues of concern for ipconazole. Future 

assessments will not probably change as it will be based on parent ipconazole alone because: (1)

ipconazole is highly persistent (90th percentile half-life= 2,483 days), (2) applied at low rate as a 

seed treatment, (3) the only degradation product that might be of concern is triazole which was 

found, in only one aerobic soil metabolism study, at relatively low concentrations (maximum 

concentration= 12% of applied parent with apparent decline). Including the degradation product 

triazole as part of the residue of concern is not expected to affect resultant exposure EDWCs for 

either surface or ground waters. In this respect, future reviews of the conazole pesticides may 

require addressing the expected contribution of ipconazole to the concentration of 1, 2, 4-triazole

degradate; a common degradation product of several conazole pesticides.

The request for new studies and additional clarification on existing environmental fate studies to 

address identified deficiencies for ipconazole is relevant for the drinking water assessment. In 

addition, more information/confirmation on the labeled use patterns is requested. Future 

estimation of the drinking water exposure will take into consideration data obtained from 

requested studies and will use official models at that time. In this respect, it is noted that current 

surface water exposure models include tier II surface water concentration calculator (SWCC 

model) for surface water exposure and PRZM ground water (PRZM-GW model) for ground 

water.

B. Clean Water Act Programs

Ipconazole was not identified as a cause of impairment for any water bodies listed as impaired 

under section 303(d) of the Clean Water Act at:

http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=88

5.

 6 Revised Estimated Drinking Water Concentrations (EDWCs) of Ipconazole from its Proposed New Use by 

expansion of Uses from Crop Subgroup 6C to the Entire Crop Group 6 for Use in Human Health Risk Assessment.
14

Furthermore, no Total Maximum Daily Load (TMDL) criteria have been developed for this 

chemical, URL: 

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

885&p_pollutant_group_name=PESTICIDES

However, an OPP aquatic life benchmarks (fresh water) have been established for ipconazole 

(refer to Table 5, below) and can be found at: URL: 

http://www.epa.gov/oppefed1/ecorisk_ders/aquatic_life_benchmark.htm.

Table 5. OPP aquatic life benchmarks (fresh water)

Fish Invertebrates

Nonvascular 

Plants

Vascular 

Plants

Office of Water Aquatic Life 

Criteria

Acute 1 Chronic 2 Acute 3 Chronic Acute Acute Maximum 

Concentration

Continuous

Concentration

Concentration (μg / L) CMC CCC

765 0.18 850 No data No data No data No data No data

1 Acute Fish= Toxicity value x LOC (Toxicity value is generally the lowest 96-hour LC50 in a 

standardized test usually with rainbow trout, fathead minnow, or bluegill; LOC= 0.5).

2 Chronic Fish= Toxicity value x LOC (Toxicity value is usually the lowest NOEAC from a life-cycle 

or early life stage test usually with rainbow trout or fathead minnow; LOC= 1).

3 Acute invertebrates= Toxicity value x LOC (Toxicity value is usually the lowest 48- or 96-hour EC50

or LC50 in a standardized test usually with midge, scud, or daphnids; LOC= 0.5.

5. Environmental Fate and Transport

In most cases, fate studies are available discretely for the cis,cis and cis,trans form of ipconazole. 

Based on submitted fate studies, ipconazole 2-[(4-Chlorophenyl) methyl]-5-(1 -methylethyl) -

1(1H- 1, 2, 4 triazole- 1 –y l methyl) cyclopentanol; CAS No. 125225-28-7; PC code 125618] is 

expected to be minimally affected by both photolysis in water and aerobic soil metabolism. The 

chemical is expected to accumulate in the top soil because of its high persistence and low 

mobility. The significance of this possible accumulation is probably relatively low due to the low 

application rates for its sole use as a seed treatment. 

Important physical/ chemical properties and abiotic transformation are summarized in Table 6

Table 6. Physical/ chemical and abiotic properties of ipconazole

Parameter Value1

Reference MRID

(Classification)

And Notes) 2

Molecular Mass 333.861 g mole-1

Molecular Formula C18H24ClN3O

Aqueous Solubility 

(mg/L @ 20 °C)

a.i (9:1 cc/ct): 6.93

cc-isomer: 6.74

ct-isomer: 3.81

45542219; Relatively high 

solubility compared to 

expected environmental 

concentrations in the seed bed.
15

Table 6. Physical/ chemical and abiotic properties of ipconazole

Parameter Value1

Reference MRID

(Classification)

And Notes) 2

Vapor Pressure (25 °C) cc-isomer: 1.6 x 10-8 torr

ct-isomer: 4.5 x 10-9 torr

Registrant data; Limited 

volatility from dry surfaces

Henry's Law Constant 

(25°C; Calculated)

cc-isomer: 1.04 x 10-9 atm.m3 mole-1

ct-isomer: 5.2 x 10-11 atm.m3 mole-1

Calculated from solubility and 

vapor pressure; Limited 

volatility from water or wet 

surfaces

n-Octanol/Water 

Partition Coefficient 

(Kow) and (log Kow)

a.i (9:1 cc/ct): 4.21 (16,218)

cc-isomer: 4.65 (44,668) or 4.29

(19,498)

ct-isomer: 4.44 (27,542) or 3.80 ( 6,310)

45542218 (A); Indicates 

possible bioaccumulation in 

aquatic organisms such as fish

Hydrolysis 

t 1⁄2 (25°C)

330 days in pH 5; 495 days in pH 7; and 

257 days in pH 9

(No Transformation products detected & 

half-lives were extrapolated beyond the 

30-day experiment duration)

45542221 (A); Data indicate 

the chemical is practically 

stable to hydrolysis

Aqueous Photolysis 

t 1⁄2 (25°C; continuous 

irradiation for 15 days)

64 days

Major degradates: None 

Minor degradates: Hydroxyl-derivative 

of ipconazole (Max. 4% @EOS) & its 

Isomer (Max. 7% @EOS)

45542222 (A); Aqueous 

photolysis is not expected to 

be important degradation 

pathway for ipconazole

Soil Photolysis t 1⁄2 No data

1 Study classification: A= Acceptable; S= Supplemental; 1 cc= cis, cis and ct= cis, trans; EOS= End of 

Study

Based on data presented in Table 6, ipconazole is expected to be readily soluble when applied 

with the seeds in an expected moist seed bed. This is due to the fact that the expected soil 

concentrations within a depth of 6” is equal to 0.064 ppm which is two orders of magnitude less 

than its reported solubility of 6.9 ppm. Volatilization of ipconazole into the air from dry/wet soils 

and water is expected to be limited due to its relatively low vapor pressure and Henry’s low 

constant. Possible bio-accumulation in fish and aquatic organisms is suggested by the relatively 

high log Kow of the isomer mixture (4.21) although the value for one of the isomers, the ctisomer is less (3.8). No bioaccumulation test was submitted in order to determine bioconcentration factors/depuration to check on conclusions drawn from values reported for the 

Octanol/Water Partition Coefficient (Kow).

Ipconazole is stable to hydrolysis and is expected to be slightly affected by photolysis especially 

in shallow/clear water bodies. Photolysis in such water bodies cause the chemical to degrade to 

hydroxyl-derivative of ipconazole and hydroxyl-derivative isomer (maximum forming 4 and 7%, 

respectively). Photolysis is not expected to be an important dissipation pathway for ipconazole.

Important fate and transport properties of ipconazole are summarized in Table 7.
16

Table 7. Fate and transport properties of ipconazole

Parameter Value

Reference 

MRID

(Classification) 1

Aerobic Soil Metabolism t 1⁄2 

(End of Study= EOS= 365 day 

study

@ 25°C)

1,386 days in a sandy loam soil (pH 6.6 and

organic matter= OM= 2.8% and cation 

exchange capacity= CEC= 21 meq/100g)

 330 days in Mutchler sandy loam soil from 

ND (pH 7.7 and OM= 9.6% and CEC= 21 

meq/100g)

2,483 days the 90th percentile half-life (n=2)

Major Degradates: 1st soil: None and 2nd soil:

Triazole averaged a maximum 1 2% @ 31 days 

and ranged from 6-9% between 59 and EOS

Minor degradates: None

Un-extracted Residues (UER): Max. 18% at 

365 d

CO2: 1% at EOS

455422-24 (S) for 

the 1st soil

And

460084-02 (A)

for the 2nd soil;

Only two soils

were used

Anaerobic/Aerobic Aquatic 

Metabolism t 1⁄2 No studies submitted

Soil Water Partition 

Coefficient (Koc)

3,214 L Kg-1 for Dock Road sandy loam soil 

from OH (pH 5.2, O.C 2.8% and CEC= 9 

meq/100);

1,911 L Kg-1 for EL7 sandy loam soil from ND 

(pH 7.1, O.C 5.6% and CEC= 23 meq/100);

2,512 L Kg-1 for Hatzenbeler clay loam soil 

from OH (pH 7.1, O.C 4.3% and CEC= 18 

meq/100);

2,813 L Kg-1 for Mutchler sandy loam soil from 

ND

(pH 5.9, O.C 1.6% and CEC= 21 meq/100); and

2,410 L Kg-1 for an Oregon silt loam soil from 

OR

(pH 5.9, O.C 2.0% and CEC= 18 meq/100).

1,724 L Kg-1 for a loam sand soil from NC

(pH 5.6-6.2, O.C 0.3% and CEC= 3 meq/100).

Average: 2,431 L Kg-1 (n= 6)

455422-25 (S)

and

468275-03 (A)

Based on the 

average of 6 soils

Aged Leaching (30-day

study)

Minimal leaching observed in Mutchler sandy 

loam soil from ND (pH 5.9, O.C 1.6% and 

CEC= 21 meq/100)

455422-26 (A)
17

Table 7. Fate and transport properties of ipconazole

Parameter Value

Reference 

MRID

(Classification) 1

Over 97% of the radioactivity (almost entirely 

parent) remained in the top 5 cm, radioactivity 

in the leachate was <0.01% and evolved CO2= 

0.2%

Terrestrial Field Dissipation t 

1⁄2 

Studies submitted not appropriate for the use 

patterns

45542227/28/29

Fish Bio-concentration No study submitted

1 Classification: A= Acceptable; S= Supplemental and 2 FAO Mobility Classification

Based on the fate and transport properties of ipconazole listed in Table 7, the chemical is highly 

persistent and degradation in soil is highly variable (t 1⁄2 ranges from 330 to 1,386 days). Longterm use in the same field may result in an accumulation of active ingredient. However, due to the 

low application rates, the long term concentration level of the chemical is expected to be low. 

Accumulation can be estimated based on applying the chemical, with seeds, yearly at a rate 

representing the maximum application rate among the many seed treatments uses. This rate was 

previously calculated to be 0.0109 lbs. a.i/A which is equal to 0.0053 ppm if the pesticide is 

assumed to be evenly distributed to a depth of 6”. Figure 1 shows an expected accumulation of 

nearly 10X the first year concentration in 20 years based on yearly applications (repeated yearly 

seeding with treated seeds) and the chemical 90th percentile half-life of 2,483 days.

Figure 1 Expected ipconazole accumulation in the soil as a result of repeated seeding with treated 

seeds

The average adsorption/desorption coefficient of 2,431 L Kg-1 suggests that the chemical is moderately mobile and 

moderate leaching is expected.

Figure 2 represents a summary of the degradation profile of ipconazole based on its 

physical/chemical and fate properties. Ipconazole is expected to be persistent in the soil system 

0.000

0.010

0.020

0.030

0.040

0.050

0 5 10 15 20

EECs in the top 6" of the soil 

(ppm)

Time (years)
18

and transported via run-off and erosion into aquatic systems. Drift may be considered minimal

with seed treatment uses. As a result of the abiotic and biotic process, low concentrations of 1, 2, 

4-triazole degradate may form which appears to decline with time.

Figure 2 Degradation profile for ipconazole

 Cl

 1,2,4- Triazole Degradate 3

Smiles Codes: 1 Parent: C1=N[N](C=N1)C[C@@]2([C@@H](CC[C@H]2CC3=CC=C(C=C3)Cl)C(C)C)O 2 Parent hydroxy derivative: C1=N[N](C=N1)C[C@@]2([C@@H](CC[C@H]2CC3=CC=C(C=C3)O[H])C(C)C)O[H]

3 Triazole degradate: C1=N[N](C=N1)[H]

The above fate and transport discussion is based upon the discrete data on the cis, cis and cis, 

trans forms of the ipconazole. However, there are uncertainties with this discussion by that there 

may be additional isomers that may actually exist within the active ingredient mixture. Refer to 

the discussion in Section 11 for further details on the nature of uncertainties and related study 

requests.

6. Receptors

Table 8 and Table 9 provide a summary of the aquatic and terrestrial taxonomic groups and most 

sensitive surrogate species tested to characterize the acute and chronic ecological effects of 

Aerobic Soil:

Very Slow Transformation 

(t 1⁄2= 330- 1,386 days

Aqueous Photolysis:

Slow transformation

expected in shallow clear 

water bodies (t 1⁄2 = 64 days). 

Very slow transformation

in deep turbid water bodies 

Ipconazole Parent 1

Hydroxyl-derivative 

Of parent ipconazole 2
19

ipconazole. 

A. Effects to Aquatic Organisms

A summary of the aquatic toxicity data has been provided in Table 8. The proceeding sections 

provide study summaries of the existing data. Ipconazole ranges from moderately toxic to highly 

toxic for freshwater fish and is moderately toxic on an acute basis to freshwater invertebrates. 

There are a number of data gaps for aquatic organisms, including all estuarine/marine data for fish 

and invertebrates as well as all aquatic plant data. A detailed summary of all available studies for 

aquatic organisms can be found in Appendix D.

Table 8 Aquatic Toxicity data for Ipconazole

Study Type Tested 

Species

Toxicity Endpoint

(ppm)

Study MRID 

and Toxicity 

Classification

Acceptability

850.1075 Acute Freshwater 

Fish (flow-through)

Rainbow 

Trout

(Oncorhynchus 

mykiss)

LC50 = 1.53

NOAEC = 0.34 

45542237

Moderately 

Toxic

Supplemental

Bluegill 

Sunfish

(Lepomis 

macrochirus)

LC50>0.73 

NOAEC = 0.73 

45542236

NA Supplemental

850.1400 Chronic 

Freshwater Fish

Fathead 

Minnow

NOAEC = 0.18 

ppm

47048902

(47104001)

NA

Acceptable

850.1010 Acute Freshwater 

Invertebrates Daphnid LC50 = 1.70 ppm

45542235

Moderately 

Toxic

Acceptable

850.1075

Acute 

estuarine/marine 

fish

No data submitted

850.1400

Chronic 

estuarine/marine 

fish

No data submitted

850.1035/ 

850.1025

Acute 

estuarine/marine 

invertebrate

No data submitted

850.1350

Chronic 

estuarine/marine 

invertebrate

No data submitted

850.440 Aquatic Vascular 

plant No data submitted

850.4550 Aquatic 

nonvascular plant No data submitted
20

B. Effects to Terrestrial Organisms

A summary of the terrestrial toxicity data has been provided in Table 9. The proceeding sections 

provide study summaries of the existing data. Ipconazole is slightly toxic to birds on an acute 

basis. On a dietary basis, ipconazole is practically nontoxic to birds. For mammals on an acute 

basis, ipconazole is moderately toxic. There are a number of data gaps for terrestrial organisms 

including an acute oral study using a passerine, a number of terrestrial invertebrate studies, and 

terrestrial plant studies. A detailed summary of all available studies for terrestrial organisms can 

be found in Appendix D.
21

Table 9 Summary of Most Sensitive Endpoints for Terrestrial Organisms to Ipconazole

Study Type Tested 

Species Toxicity Endpoint

Study MRID and 

Toxicity 

Classification

Acceptability

850.2100 Avian Acute Oral Bobwhite 

quail LD50 = 962 ppm 45542232Slightly toxic Acceptable

850.2200 Avian Dietary

Bobwhite 

quail

LC50 > 5710 ppm

NOAEC < 169 ppm

45542234

Practically nontoxic Supplemental

Mallard LC50 > 5710 ppm

NOAEC = 5710 ppm

4554233

Practically nontoxic Acceptable

850.2300 Avian Reproduction

Bobwhite 

quail NOAEC = 48.5 ppm 46020101 Acceptable

Mallard NOAEC = 97.6 ppm 46020102 Acceptable

-- Mammalian Acute 

Oral

Mouse

LD50 = 537 mg/kgbw/day (males)45552701

Moderately Toxic Acceptable

Rat LD50 = 1338mg/kgbw/day (males)

45552702

Moderately Toxic Acceptable

-- Developmental 

Toxicity Rat

NOAEC = 10 mg/kgbw/day

LOAEC = 30 mg/kgbw/day 

45552710 Acceptable

Reproductive 

Toxicity Rat

NOAEC = 8.2 

mg/kg-bw/day

LOAEC = 25.6 

mg/kg-bw/day

47048913

47048914 Acceptable

850.3020 Honeybee Acute 

Contact Study No data submitted

OECD 213 Acute Oral toxicity 

to Adult honeybees No data submitted

OECD 237 Acute Oral toxicity 

to Larval honeybees No data submitted

Non 

Guideline

Chronic Oral 

toxicity to adult 

honeybees

No data submitted

Non 

Guideline

Chronic Oral 

toxicity to Larval 

honeybees

No data submitted

Non 

Guideline

Pollinator 

feeding/semi field No data submitted

Non 

Guideline

Pollen and nectar 

residues No data submitted

Non 

Guideline

Field testing for 

Pollinators No data submitted

850.4100 Seedling Emergence No data submitted

850.4150 Vegetative Vigor No data submitted
22

C.Ecological Incidents

The Ecological Incident Information System (EIIS) is an OPP database that houses ecological 

incidents that have been reported to the Agency. When available, EIIS includes date and location 

of an incident, type and magnitude of effects observed in various species, uses 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 results from pesticide exposure. The Avian Monitoring System 

(AIMS) is a database maintained by the American Bird Conservancy that contains publicly 

available data on reported avian incidents involving pesticides. Many of the incidents listed here 

are also listed in EIIS.

A preliminary review on September 8, 2015 of EIIS did not return any incidents associated with 

ipconazole use. Additionally, The Aggregate Incident Report for EFED did not return any minor 

fish, plant or wildlife incidents; there were no avian incidents reported from AIMS. 

7. Exposure Pathways of Concern

As a seed-treatment fungicide, ingestion of treated seed placed in soil and seed dropped on soil 

surface at the time of planting is the primary pathway through which exposure may occur for 

terrestrial wildlife. The environmental fate and transport properties and use patterns of ipconazole 

indicate that runoff with eroded soil and water represent the important transport mechanisms of 

the chemical to aquatic and terrestrial organisms. Routes of exposure such as dermal contact with 

treated seed and soil will not be taken into account based on currently available models. 

Inhalation of pesticide vapors is estimated using the Screening Tool of Inhalation Risk (STIR). 

STIR estimates inhalation-type exposure based on pesticide specific information. Physical 

properties of each chemical, such as molecular weight and vapor pressure, are used to estimate 

vapor phase exposure. STIR also estimate spray droplet exposure using the application method 

(e.g. ground versus aerial spray) and rate and then compares these exposure estimates to avian and 

mammalian toxicity data. Based on the molecular weight, vapor pressure and application rate, 

inhalation exposure is not likely to be significant for ipconazole. 

SIP is used to provide an upper bound estimate of exposure of birds and mammals to pesticides 

through drinking water alone. It is used to determine whether or not drinking water exposure 

alone is a potential pathway of concern; it does not aggregate drinking water exposure with other 

exposure routes. The results of SIP conclude that drinking water exposure alone is not a potential 
23

concern for mammals on an acute basis or chronic basis. For avian species, it concludes that 

exposure through drinking water alone is not a potential concern on an acute or chronic basis. 

SIP and STIR are described in detail at: 

http://www.epa.gov/pesticides/science/models_pg.htm#terrestrial. Output from models can be 

found in Appendix B and Appendix C.

8. Analysis Plan

A. Stressors of Concern

The stressor of concern for drinking water and aquatic and terrestrial organisms is parent 

ipconazole. This decision might change because it is based on currently available data which 

indicate that the chemical is highly persistent. Degradates forming in most important 

environmental compartments, are therefore expected to be at low concentrations. Upon receiving 

requested studies, the degradation profile for the chemical will be established along with expected 

intensity of surface water exposure resulting from the chemical residues of concern. In this future 

exercise, the residues of concern will be revisited based on expected concentrations of the 

degradate 1, 2, 4-triazole and its structural similarity/toxicity to parent.

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 ipconazole will be assessed for terrestrial and aquatic exposures. 

Aquatic exposure estimates will be based on estimated environmental concentrations (EECs) 

generated using the Surface Water Concentration Calculator (SWCC) model to simulate a 

waterbody that is considered representative of vulnerable aquatic environment (e.g., ponds and 

streams in headwater watersheds). Currently, terrestrial exposure will be estimated using a model 

(T-REX version 1.5.2; March 22, 2012) and the seed treatment functions available within the 

model. Exposure to terrestrial plants will be estimated using a model (TerrPlant; version 1.2.2; 

December 26, 2006) that assumes ipconazole drifts or moves with runoff to adjacent habitats. At 

the time of risk assessment, seed treatments will be assessed based on the models available at that 

time. For more information on the various models that are currently used in the risk assessment 

see the links as outlined in Table 10. Please note that spray drift’s contribution of exposure with 

ipconazole seed treatment uses is expected to be negligible and therefore, no spray drift will be 

assumed for all aquatic and terrestrial exposure assessments.

Table 10 List of various models and the related taxa for which the models currently used

Environment Taxa of Concern Model(s)

Aquatic Fish/Invertebrates/Plants SWCC
24

Table 10 List of various models and the related taxa for which the models currently used

Environment Taxa of Concern Model(s)

Terrestrial

Vertebrate T-REX (dietary item)

Plants TerrPlant (run-off)

C. 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 ipconazole are available

D. Measures of Effect 

Toxicity data presented in Table 8 and Table 9 of this problem formulation will be used to 

calculate risk quotients in future risk assessments. Any additional information submitted by the 

registrant or found in the open literature prior to conduct of the risk assessment will also be 

considered. The open literature studies are identified using EPA’s ECOTOXicology database 

(ECOTOX), 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, Assessing Risks 

to Endangered and Threatened Species from Pesticides. The NAS report outlines 

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

pesticide risk assessments that EPA and the Services must conduct in connection with their 

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

connection with the development of its final registration review decision for ipconazole. 

In November 2013, EPA, the U.S. Fish and Wildlife Service, National Marine Fisheries (the 

Services), and USDA released a white paper containing a summary of their joint Interim 

Approaches for assessing risks to listed species from pesticides. These Interim Approaches were 

developed jointly by the agencies in response to the NAS recommendations, and reflect a 
25

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 ipconazole

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 ipconazole will describe the level of ESA analysis completed for this 

particular registration review case. This assessment will allow EPA to focus its future evaluations 

on the types of species where the potential for effects exists, once the scientific methods being 

developed by the agencies have been fully vetted. Once the agencies have fully developed and 

implemented the scientific methods necessary to complete risk assessments for listed species and 

their designated critical habitats, these methods will be applied to subsequent analyses of 

ipconazole as part of completing this registration review.

10. Endocrine Disruptor Screening Program

Ipconazole was not included in the first group of chemicals issued an order to conduct Tier 1 

EDSP testing. For additional information the EDSP program, visit http://www.epa.gov/endo/.

11. Preliminary Identification of Data Gaps 

A. Environmental Fate

A review of the available fate data reveals the following inadequacies: 

(1) Only two aerobic soil metabolism studies are available with a wide range of half-lives, a 

minimum of three is required. The registrant is requested to submit an aerobic study with at 

least one soil using the same isomer mixture present in the active ingredient and track both 

isomers. This is in addition to confirming if studies submitted earlier used the same isomer 

mixture and identifying if both isomers are biologically active and if they differ in toxicity;

(2) The registrant is requested to submit an adsorption/desorption study with one soil with an 

isomer mixture similar to the active ingredient of the pesticide. This is not required if the 

registrant confirms that previously submitted studies used the same isomer mixture present 

in the product;

(3) No anaerobic water/sediment systems were submitted and this study is required for 

modeling. In absence of this study stability will be assumed for ipconazole in the anaerobic 
26

aquatic systems;

(4) No fish bio-concentration study was submitted for this chemical. A fish bio-concentration 

study is requested due to the relatively high Kow of the isomer mixture (16,218) of 

ipconazole;

(5) No Environmental chemistry methods and associated independent validation methods were 

submitted for soil/sediment and water.

Table 11 identifies environmental fate studies by MRID that offer data for each guideline 

requirement, as well as study classifications and requested data. In addition, requested data 

needed to support the future risk assessment are listed in details earlier in the executive 

summary.

Table 11 Submitted environmental fate and transport data for ipconazole

OCSPP Guideline Data Requirement Submitted Studies 

(MRID) Study Classifications

835.2120 Hydrolysis 455422-21 Acceptable

835.2240 Aqueous photolysis 455422-22 Acceptable

835.2410 Soil photolysis No study submitted and none is required at this time

835.4100 Aerobic soil metabolism 1st study: 460084-02;

2nd study: 455422-24

1st study: Acceptable;

2nd study: Supplemental

835.4300 Aerobic aquatic metabolism

No study submitted and no study is requested at this 

time as it appears that assumption of stability is 

appropriate

835.4400 Anaerobic aquatic metabolism No study submitted and a study is requested

835.1230

835.1240

Adsorption/ desorption & 

leaching1

1st study: 468275-03;

2nd study: 455422-25;

Leaching: 455422-26

1st study: Acceptable

2nd study: Supplemental

Leaching: Acceptable

835.6100 Terrestrial field dissipation 417674-01 Submitted studies were not 

appropriate to the use

850-1730 Bio-concentration in Fish No study submitted and a study is requested

850.6100

ECM & ILV* for 

soil/sediment and 

water

None submitted. ECMs and associated ILVs for soil/sediment and water are requested.

Requested procedures are to be state-of-the-art

*ECMs= Environmental Chemistry Methods & Associated ILVs= Independent Laboratory Validations (ILVs) 1 Note: This study is not required if the registrant confirms that previous studies were conducted with an isomer mixture similar to that 

stated for the active ingredient of the pesticide

B. Ecological Effects

Table 12 and Table 13 identify ecological effects studies that offer data for each guideline

requirement, as well as study classifications and whether or not further data are needed in order to 
27

support risk assessment. Rationale for the additional data requested is presented in Table 12. 

Justification tables for non-guideline data can be found in Appendix A. 

There are a number of data gaps that must be filled to understand the full risk picture for aquatic 

species. For ipconazole, there is no data available for any estuarine/marine fish or invertebrates. 

To support the data requests and understand the potential toxicity to estuarine/marine organisms, 

the data for other conazoles were collected to understand the widespread toxicity trends across 

taxa. This data are presented in Appendix D. The data for aquatic organisms was compared 

across the 10 chemicals in the conazole class using this table. For nearly all of the acute 

estuarine/marine invertebrate studies, the conazoles are “highly toxic” on an acute basis. 

Additionally, available data for freshwater fish, freshwater invertebrates, estuarine/marine fish 

and estuarine/marine invertebrates show organisms to be more sensitive to conazoles on a chronic

basis than on an acute basis; thus submittal of chronic studies may be prioritized over acute 

studies. In order to reduce the number of studies required to understand the risk picture to aquatic 

species due to ipconazole exposure, there is the potential to employ an acute to chronic ratio. 

However, even with this method, a number of studies need to be submitted for the calculations to 

be completed. 

To employ an acute to chronic ratio to reduce the number of studies required for fish (freshwater 

and estuarine/marine), two studies will need to be submitted. Currently, there is one acute 

freshwater fish study (rainbow trout) available and one chronic freshwater fish study (fathead 

minnow) available. In order to accurately calculate an acute to chronic ratio, the species must be 

consistent across acute and chronic endpoints, therefore despite the availability of an acute and 

chronic freshwater fish study, an additional one needs to be submitted for species consistency. 

Two of the following three studies must be submitted:

• 850.1075—Acute Freshwater fish study using Fathead Minnow OR 850.1400—Chronic 

Freshwater fish study using Rainbow Trout

• 850.1075—Acute Estuarine/marine fish study 

• 850.1400—Chronic Estuarine/marine fish study

In the absence of acute and chronic data for estuarine/marine fish, the Agency will utilize the 

toxicity data from the other conazoles. Due to the complete lack of estuarine/marine species, the 

most sensitive endpoint from the conazoles in each taxa will be used for risk assessment purposes, 

based on all available data at the time of the assessment. Based on currently available date, the 

most sensitive endpoints are as follows. For acute estuarine/marine fish, an LC50 = 0.819 will be 

used in place of data for ipconazole (Difenoconazole, sheepshead minnow, MRID 42245112). 

For chronic estuarine/marine fish, a NOAEC = 0.011 mg/L will be used in place of data for 

ipconazole (Metconazole, sheepshead minnow, MRID 47795004). 

To employ an acute to chronic ratio to reduce the number of studies required for invertebrates 

(both freshwater and estuarine/marine), two studies will need to be submitted. Currently there is 

one acute freshwater invertebrate study available. Two of the following studies must be 

submitted:

• 850.1300—Freshwater invertebrate lifecycle using Daphnia magna

• 850.1025/850.1035—Acute estuarine/marine invertebrate
28

• 850.1350—Saltwater invertebrate life cycle

In the absence of acute and chronic data for freshwater and estuarine/marine invertebrates, the 

Agency will utilize the toxicity data from the other conazoles. Due to the complete lack of 

estuarine/marine species, the most sensitive endpoint from the conazoles in each taxa will be used 

for risk assessment purposes, based on all available data at the time of the assessment. Based on 

currently available data, the most sensitive species are as follows. In place of ipconazole data, 

NOAEC = 0.0056 mg/L will be used for freshwater invertebrate life cycle (Difenoconazole, 

MRID 42245114). For acute estuarine/marine invertebrates, EC50 = 0.060 mg/L will be used in 

place of data for ipconazole (Prothioconazole, mysid shrimp, MRID 46246017). For the 

estuarine/marine invertebrate lifecycle, NOAEC = 0.025 mg/L will be used in place of data for 

ipconazole (Triticonazole, mysid shrimp, MRID 46876703). The comprehensive table of 

conazole data can be found in Appendix D, along with citations each endpoint. 

In the absence of data for aquatic plant studies, a similar approach will be taken utilizing existing 

data on conazoles. 

Table 12 Submitted Aquatic Ecological Effects Data for Ipconazole

OCSPP

Guideline

Data 

Requirement

Submitted 

Studies 

(MRID)

Study 

Classifications

Are data needed 

to conduct risk 

assessment?

Justification and Assumptions EPA will 

Make in Absence of Data

850.1010 Freshwater 

invertebrate 

acute toxicity

45542235 Acceptable No --

850.1025

850.1035

Saltwater 

invertebrate 

acute toxicity 

No data 

submitted

NA Yes No acute data for estuarine/marine 

invertebrate. The data are required (R) 

under 40 CFR 158.

850.1075 Freshwater fish 

acute toxicity 

45542237 Supplemental Yes Acute data for fathead minnow is needed 

to calculate an ACR. The 40 CFR states 

that “if the test species is different from 

the two species used for the freshwater 

fish acute toxicity tests, a 96-hour LC50

on that species must also be 

provided.” Therefore, the registrant has 

two options: 1) perform another chronic 

test using the most sensitive species from 

the acute tests; or 2) perform a 96-hour 

fathead minnow study.

45542236 Supplemental

850.1075 Saltwater fish 

acute toxicity 

No data 

submitted

NA Yes Acute data for estuarine/marine fish is 

needed to calculate an ACR. The data are 

required (R) under 40 CFR 158.

In the absence of data, the Agency will 

utilize the existing data in the conazole 

chemical class. The most sensitive 

endpoint available for the given taxa will 

be used for assessment purposes. 
29

Table 12 Submitted Aquatic Ecological Effects Data for Ipconazole

OCSPP

Guideline

Data 

Requirement

Submitted 

Studies 

(MRID)

Study 

Classifications

Are data needed 

to conduct risk 

assessment?

Justification and Assumptions EPA will 

Make in Absence of Data

850.1300 Freshwater 

invertebrate 

life cycle 

47048901 Supplemental Yes Supplemental data do not provide a 

definitive endpoint and thus are 

inadequate for risk assessment purposes. 

The data are required (R) under 40 CFR 

158.

In the absence of data, the Agency will 

utilize the existing data in the conazole 

chemical class. The most sensitive 

endpoint available for the given taxa will 

be used for assessment purposes.

850.1350 Saltwater 

invertebrates 

life cycle 

No data 

submitted

NA Yes No chronic data for estuarine/marine 

invertebrates. The data are required (R) 

under 40 CFR 158.

In the absence of data, an acute to chronic 

ratio may be calculated to estimate the 

toxicity of ipconazole to estuarine/marine 

invertebrates on a chronic basis. 

Calculation of an ACR requires the 

submission of acceptable studies of both 

the freshwater invertebrate life cycle, and 

estuarine/marine acute toxicity study.

In the absence of data available to 

calculate the ACR, the Agency will utilize 

the existing data in the conazole chemical 

class. The most sensitive endpoint 

available for the given taxa will be used 

for assessment purposes.

850.1735 Whole Sediment 

Acute toxicity 

10-day

No data 

submitted

NA Yes No sediment data available for freshwater 

organisms. Data is required based on the 

Koc of the chemical.

850.1400 Freshwater fish 

early-life stage

47048902 Acceptable Yes Freshwater fish early-life stage data using 

a rainbow trout is needed to calculate an 

ACR. The 40 CFR states that “if the test 

species is different from the two species 

used for the freshwater fish acute toxicity 

tests, a 96-hour LC50 on that species must 

also be provided.” Therefore, the 

registrant has two options: 1) perform 

another chronic test using the most 

sensitive species from the acute tests; or 

2) perform a 96-hour fathead minnow 

study.
30

Table 12 Submitted Aquatic Ecological Effects Data for Ipconazole

OCSPP

Guideline

Data 

Requirement

Submitted 

Studies 

(MRID)

Study 

Classifications

Are data needed 

to conduct risk 

assessment?

Justification and Assumptions EPA will 

Make in Absence of Data

850.1400 Saltwater fish 

early-life stage 

No data 

submitted

NA Yes No chronic data for estuarine/marine fish. 

The data are required (R) under 40 CFR 

158.

In the absence of data, an acute to chronic 

ratio may be calculated to estimate the 

toxicity of ipconazole to estuarine/marine 

invertebrates on a chronic basis. 

Calculation of an ACR requires the 

submission of an acceptable study for 

estuarine/marine acute toxicity to fish, 

and the submission of an acute freshwater 

fish conducted using the fathead minnow. 

In the absence of data necessary to 

calculate the ACR, the Agency will utilize 

the existing data in the conazole chemical 

class. The most sensitive endpoint 

available for the given taxa will be used 

for assessment purposes.

850.1500 Fish life cycle No Data 

submitted

NA No --

850.4400 Aquatic plant 

Toxicity Test 

using Lemna 

spp.

No data 

submitted

NA Yes No aquatic vascular plant data available. 

The data are required under 40 CFR 158. 

In the absence of data, the Agency will 

utilize the existing data in the conazole 

chemical class. The most sensitive 

endpoint available for the given taxa will 

be used for assessment purposes. 

850.4500 Algal toxicity No data 

submitted

NA Yes No aquatic nonvascular plant data 

available. The data are required under 40 

CFR 158.

In the absence of data, the Agency will 

utilize the existing data in the conazole 

chemical class. The most sensitive 

endpoint available for the given taxa will 

be used for assessment purposes.
31

Table 13 Terrestrial Ecological Effects Data for Ipconazole

OCSPP 

Guideline

Data 

Requirement

Submitted 

Studies 

(MRID)

Study 

Classifications

Are data 

needed for 

risk 

assessment?

Justification and Assumptions EPA will Make 

in Absence of Data

850.2100 Avian oral 

toxicity

45542232

(Bobwhite)

Acceptable Yes In addition to existing acuta oral data using a 

Bobwhite, acute oral toxicity data for a passerine 

species are required under 40 CFR Part 158. A 

study has not been submitted for this data 

requirement. 

A guideline-compliant passerine acute oral 

toxicity test is needed. Acute oral toxicity data 

are only available for one avian species (i.e., 

bobwhite quail). Passerine birds may utilize 

metabolic pathways that are different from larger 

birds and therefore be more sensitive to 

ipconazole. Furthermore, passerines exhibit 

behavioral responses to pesticide dosing that are 

potential indicators of reduced fitness in the field 

(e.g., regurgitation of contaminated diet) even 

when direct biochemically-mediated lethal 

toxicity is not apparent. 

850.2200 Avian dietary 

toxicity 

45542234 Supplemental No --

45542234 Acceptable

850.2300 Avian 

reproduction

46020101 Acceptable No --

46020102 Acceptable

850.3030 Residues in 

Foliage

No data 

submitted

NA No This study is not currently considered a data gap 

because exposure via residues in foliage is not 

consistent with a seed treatment use.

850.3020 Honey bee 

acute contact 

toxicity

No data 

submitted

NA Yes As part of the Guidance for assessing pesticide 

risks to bees (USEPA, 2014), the following Tier I 

studies are recommended:

• Acute oral toxicity to adult honey bees

• Acute oral toxicity to larval honey bees

• Chronic oral toxicity to adult honey bees

• Chronic oral toxicity to larval honey bees

In the absence of these data, honey bee oral 

toxicity data for surrogate pesticides – starting 

with data for closely related pesticides (e.g., 

diphenyl ethers) and proceeding to data for less 

related pesticides – may be used to characterize 

the oral toxicity of ipconazole to larval and adult 

honey bees. 

OECD 213 Acute oral 

toxicity to 

adult honey 

bees

No data 

submitted

NA Yes

OECD 237 Acute oral 

toxicity to 

larval 

honeybees

No data 

submitted

NA Yes

Non 

Guideline

Chronic oral 

toxicity to 

adult honey 

bees

No data 

submitted

NA Yes
32

Non 

Guideline

Chronic oral 

toxicity to 

larval honey 

bees

No data 

submitted

NA Yes Tier II (feeding/semi-field/pollen and nectar 

residue) and Tier III (full field) studies may be 

needed, contingent upon the results of lower tier 

studies. 

Non 

Guideline

Pollinator 

feeding/semifield (Tier II)

No data 

submitted

NA Need for 

data 

contingent 

upon 

results of 

Tier I bee 

studies

Non 

Guideline

Pollen and 

nectar residue 

studies (Tier 

II)

No data 

submitted

NA Need for 

data 

contingent 

upon 

results of 

Tier I bee 

studies

850.3040 Field testing 

for pollinators

(Tier III) 

No data 

submitted

NA Need for 

data 

contingent 

upon 

results of 

Tier I bee 

studies

850.4100 Seedling 

Emergence 

and Seedling 

Growth

No data 

submitted

NA Yes No vascular terrestrial plant data available. Data 

are required under 40 CFR 158.

850.4150 Vegetative 

Vigor

No data 

submitted

NA No This data is not required because exposure is not 

expected based on use as a seed treatment only.
33

12. References

Guidance for assessing pesticide risks to bees (USEPA, 2014): URL: 

http://www2.epa.gov/sites/production/files/2014-

06/documents/pollinator_risk_assessment_guidance_06_19_14.pdf

125618 (Ipconazole) Fate Chemistry Bibliography 05/14/12

161-1 Hydrolysis

MRID Citation Reference

45542221 Hatzenbeler, C.; Long, M. (2001) A Hydrolysis Study of (Carbon 14) 

Ipconazole in Water: Amended Report: Lab Project Number: 012130-1-2: 

012130: 2000-094. Unpublished study prepared by Ricerca, LLC. 55 p. 

161-2 Photo degradation-water

45542222 Shah, J. (2001) A Photolysis Study of (Carbon 14) Ipconazole in Water: 

Amended Report: Lab Project Number: 012540-1-1: 012540: 2000-126. 

Unpublished study prepared by Ricerca, LLC. 62 p. 

162-1 Aerobic soil metabolism

45542223 Shocken, M.; Nag, J. (2001) Aerobic Soil Metabolism of (Carbon 14) 

Ipconazole in a North Dakota Sandy Loam: A Progress Update: Lab 

Project Number: 2001-125. Unpublished study prepared by Uniroyal 

Chemical Co. 13 p. 

45542224 Hatzenbeler, C.; Shah, J. (2001) An Aerobic Soil Metabolism Study with 

(Carbon 14) Ipconazole: Amended Report: Lab Project Number: 012131-

2-1: 012131: 2000-095. Unpublished study prepared by Ricera, LLC. 74 

p. 

46008402 Nag, J. (2002) Aerobic Soil Metabolism of (Carbon 14)-Ipconazole in a 

North Dakota Sandy Loam. Project Number: 2001/010, 41/6173. 

Unpublished study prepared by Springborn Smithers Laboratories; Agvise 

Laboratories and Crompton Corporation. 191 p.

163-1 Leach/adsorp/desorption

45542225 Hatzenbeler, C.; Long, M. (2001) Adsorption and Desorption of (Carbon 

14) Ipconazole in Soils: Amended Report: Lab Project Number: 012538-

1-1: 012538: 2000-127. Unpublished study prepared by Ricera, LLC. 102 

p. 
34

45542226 Hatzenbeler, C.; Repko, T. (2001) An Aged Column Leaching Study of 

(Carbon 14) Ipconazole in Soils: Lab Project Number: 012535-1-1: 

012535: 2000-128. Unpublished study prepared by Ricera, LLC. 61 p. 

46827503 Wanner, U. 2006. [14C]-Ipconazole: adsorption/desorption to a loamy 

sand (batch equilibrium method). Unpublished study performed, 

sponsored, and submitted by Chemtura Corporation, Middlebury, 

Connecticut. The microbial activity of the test soil was performed by 

Agvise Laboratories, Northwood, North Dakota. Crompton Study No.: 

2005-035. The study was initiated October 19, 2005 and completed April 

18, 2006; experimental start and completion dates not reported (p. 6). 

Final report issued April 26, 2006.

164-1 Terrestrial field dissipation

45542227 Eiji, Y. (2001) Soil Dissipation Study of KNF-317 (Submerged Soil In 

Vitro) Analysis of the Parent Compounds in Ushiku-Soil, Fukui-Soil and 

Kikukawa-Soil: Ipconazole Technical. Unpublished study prepared by 

Kureha Chemical Industry Co. Ltd. 47 p. 

45542228 Eiji, Y. (2001) Soil Dissipation Study of KNF-317 (Submerged Soil in the 

Fields) Analysis of the Parent Compounds in Ushiku-Soil, Fukui-Soil and 

Kikukawa-Soil: Ipconazole Technical: Lab Project Number: 37. 

Unpublished study prepared by Kureha Chemical Industry Co., Ltd. 53 p. 

45542229 Isao, I. (2001) Soil Dissipation Study of KNF-317 (Upland Soil In Vitro) 

Analysis of the Parent Compounds in Ushiku-Soil, Fukui-Soil and 

Kikukawa-Soil Analysis of the Metabolites in Ushiku-Soil and KouchiSoil: Ipconazole Technical: Lab Project Number: 40. Unpublished study 

prepared by Kureha Chemical Industry Co., Ltd. 52 p. 
35

125618 Ipconazole Eco Effects Bibliography 

71-1 Avian Single Dose Oral Toxicity

MRID Citation Reference

45542232 Gallagher, S.; Beavers, J. (2000) Ipconazole: An Acute Oral Toxicity Study with 

the Northern Bobwhite: Lab Project Number: 117-181. Unpublished study 

prepared by Wildlife International, Ltd. 36 p. {OPPTS 850.2100} 

71-2 Avian Dietary Toxicity

MRID Citation Reference

45542233 Gallagher, S.; Beavers, J.; Martin, K. (2000) Ipconazole: A Dietary LC50 Study 

with the Mallard: Lab Project Number: 117-180. Unpublished study prepared by 

Wildlife International, Ltd. 53 p. {OPPTS 850.2200} 

45542234 Gallagher, S.; Beavers, J.; Martin, K. (2000) Ipconazole: A Dietary LC50 Study 

with the Northern Bobwhite: Lab Project Number: 117-179. Unpublished study 

prepared by Wildlife International, Ltd. 55 p. {OPPTS 850.2200} 

46509901 Registrant 

Response

Crompton Corp.; Wildlife International (2005) Ipconazole Technical (400-512): 

Crompton Response to Ecotox Registration Conditions for New Uses. 

Unpublished study prepared by Crompton Manufacturing Co., Inc. and Wildlife 

International, Ltd. 33 p.

71-4 Avian Reproduction

MRID Citation Reference

46020101 Temple, D.; Grimes, J.; Martin, K.; et. al. (2003) Ipconazole: A Reproduction 

Study with the Mallard: Final Report. Project Number: 117-185. Unpublished 

study prepared by Wildlife International, Ltd. 183 p.

46020102 Temple, D.; Grimes, J.; Martin, K.; et. al. (2003) Ipconazole: A Reproduction 

Study with the Northern Bobwhite: Final Report. Project Number: 117/184. 

Unpublished study prepared by Wildlife International, Ltd. 183 p. 

72-1 Acute Toxicity to Freshwater Fish

MRID Citation Reference

45542236 Palmer, S.; Kendall, T.; Krueger, H. (2001) Ipconazole: A 96-Hour FlowThrough Acute Toxicity Test with the Bluegill (Lepomis macrochirus): Final 

Report: Lab Project Number: 117A-117. Unpublished study prepared by Wildlife 

International, Ltd. 44 p. {OPPTS 850.1075} 

45542237 Palmer, S.; Kendall, T.; Krueger, H. (2001) Ipconazole: A 96-Hour FlowThrough Acute Toxicity Test with the Rainbow Trout (Oncorhynchus mykiss): 
36

Final Report: Lab Project Number: 117A-118. Unpublished study prepared by 

Wildlife International, Ltd. 44 p. {OPPTS 850.1075} 

46509901 Registrant 

Response

Crompton Corp.; Wildlife International (2005) Ipconazole Technical (400-512): 

Crompton Response to Ecotox Registration Conditions for New Uses. 

Unpublished study prepared by Crompton Manufacturing Co., Inc. and Wildlife 

International, Ltd. 33 p.

72-2 Acute Toxicity to Freshwater Invertebrates

MRID Citation Reference

45542235 Palmer, S.; Kendall, T.; Krueger, H. (2001) Ipconazole: A 48-Hour FlowThrough Acute Toxicity Test with the Caldoceran (Daphnia magna): Final 

Report: Lab Project Number: 117A-116B. Unpublished study prepared by 

Wildlife International, Ltd. 46 p. {OPPTS 850.1010} 

850.1300 Daphnid chronic toxicity test

MRID Citation Reference

47048901 memo Flatman, D. (2007) Ipconazole: Prolonged Toxicity to Daphnia magna. Project 

Number: KRA/130, KRA/130/053946. Unpublished study prepared by 

Huntingdon Life Sciences, Ltd. 90 p.

47632604 Registrant 

Response

Dupre, M. (2008) Response to the EPA Data Evaluation Report [D337783] on 

the Chronic Toxicity of Ipconazole to Freshwater Invertebrates - Daphnia sp., 

KRA/130. Project Number: KRA/130, KRA/130/053946, KRA/129/053945. 

Unpublished study prepared by Huntingdon Life Sciences, Ltd. 15 p.

850.1400 Fish early-life stage toxicity test

MRID Citation Reference

47048902 memo Burke, J. (2007) Ipconazole: Fish Early Life Stage Toxicity Test for Fathead 

Minnow. Project Number: KRA/129, KRA/129/053945. Unpublished study 

prepared by Huntingdon Life Sciences, Ltd. 92 p.

47104001 memo Burke, J. (2007) Ipconazole: Fish Early Stage Toxicity Test for Fathead 

Minnow: Final Report. Project Number: KRA/129, KRA/129/053945. 

Unpublished study prepared by Huntingdon Life Sciences, Ltd. 92 p.

72-5 Life cycle fish

MRID Citation Reference

46509901 Registrant 

Response

Crompton Corp.; Wildlife International (2005) Ipconazole Technical (400-512): 

Crompton Response to Ecotox Registration Conditions for New Uses. 

Unpublished study prepared by Crompton Manufacturing Co., Inc. and Wildlife 

International, Ltd. 33 p.

850.1075 Fish acute toxicity test, freshwater and marine
37

MRID Citation Reference

46509901 Crompton Corp.; Wildlife International (2005) Ipconazole Technical (400-512): 

Crompton Response to Ecotox Registration Conditions for New Uses. 

Unpublished study prepared by Crompton Manufacturing Co., Inc. and Wildlife 

International, Ltd. 33 p.

850.2200 Avian dietary toxicity test

MRID Citation Reference

46509901 Registrant 

response

Crompton Corp.; Wildlife International (2005) Ipconazole Technical (400-512): 

Crompton Response to Ecotox Registration Conditions for New Uses. 

Unpublished study prepared by Crompton Manufacturing Co., Inc. and Wildlife 

International, Ltd. 33 p.

Non Guideline

MRID Citation Reference

46509901 Some

discussion in

Memo

Crompton Corp.; Wildlife International (2005) Ipconazole Technical (400-

512): Crompton Response to Ecotox Registration Conditions for New 

Uses. Unpublished study prepared by Crompton Manufacturing Co., Inc. 

and Wildlife International, Ltd. 33 p.

This response repeated for Guidelines 72-5, 850-1300, 72-1, 71-2

45542238 Wilkinson, C. (2001) The Magnitude, Nature and Toxicological 

Significance of Crop Residues of Ipconazole. Unpublished study 

prepared by C. Wilkinson, LLC. 12 p. 

45548301 Rockwell, J. (2001) Reduced-Risk Pesticide Rationale for Ipconazole: 

Lab Project Number: ADMIN/IPC/RR-1. Unpublished study prepared by 

Rockwell Enterprises, Inc. 138 p

48311205 Friedlander, B. (2010) Validation of an Analytical Method for the 

Determination of Clothianidin, Ipconazole and Metalazyl in Inovate Seed 

Protectant: Final Report Amendment - 01. Project Number: GRL/12911, 

201000296. Unpublished study prepared by Chemtura Canada Co./Cie. 

69 p.

48720703 Friedlander, B. (2013) Validation of an Analytical Method for the 

Determination of Clothianidin, Ipconazole and Metalaxyl in Inovate Pro, 

UBI 7004-00. Project Number: GRL/13225. Unpublished study prepared 

by Chemtura Canada Co./Cie. 79p.
38

Appendix A. Example of SIP Input

Table 1. Inputs

Parameter Value

Chemical name Ipconazole

Solubility (in water at 25oC; mg/L) 6.9

Mammalian LD50 (mg/kg-bw) 537

Mammalian test species other

Body weight (g) of "other" mammalian species 25

Mammalian NOAEL (mg/kg-bw) 8.2

Mammalian test species laboratory rat

Body weight (g) of "other" mammalian species

Avian LD50 (mg/kg-bw) 962

Avian test species northern bobwhite quail

Body weight (g) of "other" avian species

Mineau scaling factor 1.15

Mallard NOAEC (mg/kg-diet) 587

Bobwhite quail NOAEC (mg/kg-diet) 169

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) 1.1868 1.1868

Adjusted toxicity value (mg/kg-bw) 213.5302 6.3071

Ratio of exposure to toxicity 0.0056 0.1882

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) 5.5890 5.5890

Adjusted toxicity value (mg/kg-bw) 693.0532 17.9644

Ratio of exposure to acute toxicity 0.0081 0.3111

Conclusion*

Drinking water exposure 

alone is NOT a potential 

concern for birds

Drinking water exposure 

alone is NOT a potential 

concern for birds
39

*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.
40

Appendix B. Example of STIR Output

Screening Tool for Inhalation Risk

This tool is designed to provide the risk assessor with a rapid method for determining the potential

significance of the inhalation exposure route to birds and mammals in a risk assessment.

Input

Application and Chemical Information

Enter Chemical Name Ipconazole

Enter Chemical Use Turf

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

If Spray What Type (enter ground or air) ground

Enter Chemical Molecular Weight (g/mole) 345.2

Enter Chemical Vapor Pressure (mmHg) 1.00E-06

Enter Application Rate (lb a.i./acre) 4

Toxicity Properties

Bird

Enter Lowest Bird Oral LD50 (mg/kg bw) 2150

Enter Mineau Scaling Factor 1.15

Enter Tested Bird Weight (kg) 0.178

Mammal

Enter Lowest Rat Oral LD50 (mg/kg bw) 5000

Enter Lowest Rat Inhalation LC50 (mg/L) 1.94

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) 1.86E-02

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 2.34E-03

Adjusted Inhalation LD50 4.65E+00

Ratio of Vapor Dose to Adjusted Inhalation LD50 5.02E-04 Exposure not Likely Significant

Maximum Post-treatment Spray Inhalation Dose (mg/kg) 4.23E-01

Ratio of Droplet Inhalation Dose to Adjusted Inhalation LD50 9.09E-02 Exposure not Likely Significant

Results Mammalian (0.015 kg )

Maximum Vapor Concentration in Air at Saturation (mg/m3) 1.86E-02

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 2.94E-03

Adjusted Inhalation LD50 1.15E+02

Ratio of Vapor Dose to Adjusted Inhalation LD50 2.54E-05 Exposure not Likely Significant

Maximum Post-treatment Spray Inhalation Dose (mg/kg) 5.31E-01

Ratio of Droplet Inhalation Dose to Adjusted Inhalation LD50 4.60E-03 Exposure not Likely Significant
41

Appendix C. Full Study Details for all Toxicity Studies

Freshwater Fish Toxicity Data

There are two studies available measuring the acute toxicity of ipconazole to fish; both are 

classified as supplemental. MRID 45542237 measured the acute toxicity of ipconazole to 12-

week old rainbow trout (Oncorhynchus mykiss) under flow-through conditions. Fish were 

exposed to ipconazole at nominal concentrations of 0 (negative control), 0 (0.1 mL/L acetone 

control), 0.31, 0.63, 1.3, 2.5 and 5.0 ppm. Mean-measured centrifuged concentrations were 

<0.01 – 0.10 (LOQ; controls), 0.13, 0.34, 0.76, 1.4 and 2.1 ppm ai. After 96 hours of exposure, 

cumulative mortality was 0% in the controls and lowest three test concentrations; it was 20% in 

the 1.4 ppm ai treatment group and 100% in the 2.1 ppm ai treatment group. This categorizes 

ipconazole as moderately toxic to rainbow trout on an acute toxicity basis. Sublethal effects were 

observed in surviving fish from the 0.76, 1.4 and 2.1 ppm ai groups between 6 and 96 hours and 

included lying on the bottom with little motion and loss of equilibrium. The NOAEC for 

mortality/ immobilization was 0.76 ppm ai and the NOAEC for sublethal effects was 0.34 ppm 

ai. The study is considered to be scientifically sound and was classified as supplemental; the 

dilution series used produced only one partial kill, thus a precise 96-hour LC50 and 95% 

confidence interval cannot be determined. The guidance recommends each tested concentration 

should be 60% of the next highest concentration rather than the 50% used in this test design.

MRID 45542236 measured the acute toxicity of ipconazole to 10-week old bluegill sunfish 

(Lepomis macrochirus) under flow-through conditions. Fish were exposed to ipconazole at 

nominal concentrations of 0 (negative control) 0 (0.1 mL/L acetone control), 0.31, 0.63, 1.3, 2.5 

and 5.0 ppm ai. Mean-measured centrifuged concentrations were <0.0150- 0.150 (LOQ; 

control), 0.14, 0.33, 0.73, 1.8 and 2.4 ppm ai. After 96 hours of exposure, cumulative mortality 

was 0% in the lowest 3 treatment groups, 90% in the 1.8 ppm ai treatment group and 100% in the 

2.4 ppm ai treatment group. 100% of the mortality occurred at the 2.4 ppm ai within the first 24 

hours. The high percentage of fish killed in the highest concentrations produced an estimated 

LC50 lower than the LOAEC. Thus the LC50 can be approximated at >0.73 ppm ai. This 

categorizes ipconazole as either highly toxic or moderately toxic to the bluegill sunfish on an 

acute toxicity basis, depending on whether or not the actual 96-hr LC50 exceeds 1 ppm. Sublethal 

effects were observed in the surviving fish from the 1.8 ppm ai between 24 and 96 hours and 

included lying on the bottom with little motion, loss of equilibrium, erratic swimming, lethargy, 

and floating with little or no movement. The NOAEC and LOAEC observed for mortality and 

sublethal effects were 0.73 and 1.8 ppm ai respectively. This study is considered scientifically 

sound and was classified as supplemental. The dilution series produced only one partial kill, thus 

a precise 96-hr LC50 cannot be determined. Because the two kills produced were 80% and 100%, 

the calculated LC50 is less than the LOAEC and the NOAEC is equal to the lower bound of the 

95% of the confidence interval. Additionally, the guidance dictates each tested concentration 

should be 60% of the next highest concentration rather than the 50% used in this test design.

In response to the 2004 assessment, there was a request to upgrade the studies from supplemental 

to acceptable. The request was responded to under D315933 and determined that EFED would 

maintain the supplemental classification based on the uncertainty of the data. New studies will 
42

be requested in accordance with 850.1075 guidance.

There is one study available measuring the effects of chronic exposure of early life stage fathead 

minnow to ipconazole under flow-through conditions. MRID 47104001 (also filed under MRID 

47048902) was classified as acceptable. Fertilized eggs/embryos (60/level, <48 hours old) of 

fathead minnows were exposed to nominal concentrations of 0 (negative and solvent controls), 

0.077, 0.19, 0.48, 1.2, and 3.0 μg ai/L. No treatment related effects on the time to hatch or 

hatchling success were observed. The majority of embryos from all control and treatment levels 

hatched on day 4, and cumulative percent hatch averaged 87% in the negative control group, 98% 

in the solvent control group, and 95 – 100 % for all treatment levels. Post-hatch survival was 

adversely affected by treatment; survival averaged 92% in the negative control group, 90% in the 

solvent control group, and 81, 84, 67 80, and 22% for the treatment levels, respectively. There 

appeared to be a treatment-related increase in the incidence of elongated, lethargic, and/or pale 

fish at the 2.8 μg ai/L level compared to the controls and lower treatment levels. Statistically 

significant reductions were detected at the 1.1 and 2.8 μg ai/L treatment levels for wet weight and 

at the 2.8 μg ai/L treatment level for length. Mean length ranged from 15.5-16.8 mm for the 

negative control, solvent control and < 0.44 μg ai/L test levels, and 14.9 and 11.3 for the 1.1 and 

2.8 μg ai/L treatment levels, respectively. Dry weight ranged from 7.0 to 9.4 mg for the negative 

control, solvent control and <0.44 μg ai/L test concentrations, and 4.3 and 1.5 mg for the 1.1 and 

2.8 μg ai/L treatment levels, respectively. 

There are two test reports corresponding with this study; the amended report was submitted to 

identify a LOAEC, correct the NOAEC for mortality and to change the effective concentrations 

identified for dry weights in the initial report. EFED analysis of the data identified the post hatch 

survival of the fathead minnow as the most sensitive endpoint; the visually determined NOAEC 

value for the post-hatch survival is 0.18 ppb based on significant survival inhibition at the 0.44 

ppb level. The analysis concluded that the 0.44 ppb level cannot be precluded in view of the 

treatment-related effects on post hatch survival at this level. Therefore the NOAEC and LOAEC 

values for post-hatch survival of 0.18 and 0.44 ppb, respectively, will be used in risk analysis. 

Freshwater Invertebrates Toxicity Data

There is one study available to analyze the toxicity of ipconazole to freshwater invertebrates. 

MRID 45542235 examined the 48-hour acute toxicity of ipconazole to Daphnia magna under 

flow-through conditions. Neonate daphnids were exposed to the test material at nominal 

concentrations of 0 (negative control), 0 (0.1 mL/L DMF control), 0.31, 0.63, 1.3, 2.5 and 5.0 

ppm. Mean-measured centrifuged concentrations were <0.01-0.10 (LOQ, controls), 0.13, 0.35, 

0.76, 1.6 and 3.3 ppm ai. By 48 hours, mortality was 0% in the controls and 0.13 ppm ai test 

group; it was 5%, 35% 30% and 80% in the remaining treatment groups, respectively. The 

calculated 45-hr LC50 was 1.70 ppm ai (95% C.I. 1.23-2.63 ppm) which categorizes ipconazole as 

moderately toxic to Daphnia magna on an acute toxicity basis. Lethargy was observed in 

surviving daphnids from the >0.35 ppm ai groups. The 48-hour NOAEC level, based on both 

mortality/immobility and sub-lethal (lethargy) effects was 0.13 ppm ai, the lowest concentration 

tested. The study was classified as acceptable.
43

A chronic freshwater invertebrate life cycle study (MRID 47048901) evaluating ipconazole’s 

effect on Daphnia magna was classified as invalid. The scientific soundness of the study was 

questionable for a number of reasons, including: statistically significant reproduction differences 

between the solvent control and negative control, use and combining of concentrations and data 

from 2 separate tests to derive endpoints, highly variable offspring production data between the 

tests, and the use of neonates from two stock cultures. The study was re-examined as part of a 

follow-up under D330267 in 2007. EFED continues to consider the study to be invalid and 

requires a new study to evaluate the chronic exposure effects of ipconazole on Daphnia magna.

Chemtura submitted a response to the DER, under MRID 47632604, requesting the requirement 

for a new chronic study conducted using Daphnia magna be waived. EFED responded to this 

request under D361764, stating that the study (MRID 47048901) would be upgraded from invalid 

to supplemental, however the study was unable to derive a definitive endpoint. 

Avian Toxicity Data

MRID 45542232 evaluates the acute oral toxicity of ipconazole to 18-week old bobwhite quail 

(Colinus virginianus). Ipconazole was administered to the birds by gavage (via oral capsule) at 

nominal concentrations of 0, 31.3, 62.5, 125, 250, 500, 1000 and 2000 mg/kg-bw. After 14 days, 

mortality was 0% in the control and <500 mg/kg test levels, 70% in the 1000 mg/kg test level and 

90% in the 2000 mg/kg-bw test level. The acute LD50 was 962 mg/kg (95% C.I 716-1300 

mg/kg). Thus, ipconazole is categorized as slightly toxic to northern bobwhite quail on an acute 

oral basis. Clinical signs of toxicity were observed in the > 500 mg/kg test birds between days 0 

and 10 and included ruffled appearance, lethargy, depression, wing droop, reduced reaction to 

external stimuli, lower limb weakness, loss of coordination, and/or emaciation. The NOAEC for 

clinical effects was 250 mg/kg. Treatment related dose-responsive reductions in body-weight 

were observed in both sexes from the > 62.5 mg/kg test groups between days -1 and 3. At the 

62.5 through 250 mg/kg levels, birds began to recover by exhibiting weight gains between days 3 

and 7, and at the >500 mg/kg levels, surviving birds exhibited weight gains between 7 to 14 days. 

The NOAEC for body weight was 31.3 mg/kg (both sexes). Between days 0 to 3, treatment 

related reductions in food consumption were observed in females from the 500 mg/kg level, and 

in both sexes of birds in the 1000 and 2000 mg/kg groups. The reductions continued in surviving 

females from the 1000 and 2000 mg/kg groups between days 4 and 7. The NOAEC for food 

consumption was 500 mg/kg for males and 250 mg/kg for females. Necropsy of decedent birds 

revealed a thin or emaciated body condition with a loss of muscle mass and prominent keel, 

discoloration of the spleen, pale kidneys, empty crop, congested capillaries in the crop and in 

several cases, a flaccid gizzard. Necropsy of birds surviving test termination revealed one 500 

mg/kg male that was emaciated, with a loss of muscle mass, prominent keel and pale kidneys; one 

1000 mg/kg male that had a thickened inner crop lining and foam in the crop; and the 2000 mg/kg 

female was thin. This study has been classified as acceptable.

Two studies are available to establish the dietary toxicity of ipconazole to avian species. In 

MRID 45542234, the acute dietary toxicity of ipconazole to 10-day old northern bobwhite 

(Colinus virginianus) was assessed over 8 days. Ipconazole was administered to the birds in the 

diet at nominal concentrations of 0, 178, 316, 562, 1000, 1780, 3160, and 5620 ppm. Mean 

measured concentrations were <1.5 (LOQ), 169, 318, 587, 984, 1760, 2990 and 5710 ppm ai. 

Mortality was 0% in the 169, 318, and 984 ppm ai test groups, 33% in the 587 ppm ai group, 20% 

in the 1760 ppm ai group, 10% in the 2990 ppm ai group and 30% in the 5710 ppm ai group. 
44

Data did not exhibit a standard dose-response curve, and a reliable LC50 cannot be calculated from 

the study data. The estimated LC50 exceeds the highest test concentrations, 5710 ppm ai. 

Guideline criteria require <20% kill at 5000 ppm ai to classify a compound as having an LC50> 

5000 ppm ai. The estimated LC50 categorizes ipconazole as practically non-toxic to the bobwhite 

quail on an acute dietary basis. The NOAEC for mortality was 318 ppm ai. Clinical signs of 

toxicity were observed through day 7 in surviving birds at the > 587 ppm ai test levels, and 

included ruffled appearance, lethargy, reduced reaction to external stimuli, wing droop, and/or 

slight loss of coordination. The NOAEC for clinical effects was 318 ppm ai. Concentrationresponsive reductions in body weight changes were observed during the 5-day exposure period in 

all test levels, with a statistically significant effect noted at 169 ppm ai, the lowest concentration 

tested. Compared to the controls, a significant increase in feed consumption was noted at the 587 

ppm ai. This group consumed the greatest amount of food of all the treatment levels and also had 

the highest mortality level. A significant decrease in food consumption during day 0-5 was noted 

in doses > 1760 ppm. Whether this decrease was due to toxic anorexia or avoidance of 

contaminated food is unknown. Because the test did not produce a definitive LC50, the study is 

classified as supplemental.

MRID 45542233 established the acute dietary toxicity of ipconazole to 10-day old mallard ducks 

(Anas platyrhynchos) over 8 days. Ipconazole was administered to the birds in the diet at nominal 

concentrations of 0, 178, 316, 562, 1000, 1780, 3160, and 5620 ppm. Mean measured 

concentrations were <1.5 (LOQ), 169, 318, 587, 984, 1760, 2990 and 5710 ppm ai. No mortality 

was observed during the study. The 8-day acute dietary LC50 was >5710 ppm ai, which 

categorizes ipconazole as practically non-toxic to mallard duck on an acute dietary basis. No 

clinical signs of toxicity were noted at any treatment level. Concentration-responsive reductions 

in body weight gains were observed during the 5-day exposure period at the >984 ppm ai levels, 

which also resulted in overall (0-8 days) weight reductions compared to the control. Food 

consumption decreased in the 5710 ppm treatment group, but resulted were not statistically 

significant. During the exposure period, body weight gains were 148 g for the control group, and 

151, 159, 153, 132, 124, 98 and 54 g for the 169, 318, 587, 984, 1760, 2990 and 5710 pp ai 

groups, respectively. NOAEC was 587 ppm ai based on body weight changes (day 0 to 5). This 

toxicity test is scientifically sound and classified as acceptable.

There are two studies available to measure the reproductive effects in birds due to ipconazole 

exposure. MRID 46020101 is a one-generation reproductive toxicity test to groups (16 

pens/treatment level) of 1 male and 1 female, 23-week old mallard ducks, over approximately 21 

weeks. Ipconazole was administered to the birds in the diet at mean-measured concentrations of 

<5 (LOD, negative control), 22.4, 48.5, 97.6, or 197 ppm ai. Nominal concentrations were 0, 25, 

50, 100 and 200 ppm. A statistically significant treatment-related effect was noted in the live 

embryo/viable embryo percentages at the 97.6 ppm ai and 197 ppm ai treatment levels. The 

NOAEC is 197 ppm ai and the LOAEC is >197 ppm ai. The study report notes, that because the 

NOAEC is the highest dosage tested, and no LOAEC was determined, considerable uncertainty is 

associated with both values, and this uncertainty should be considered when making assessments 

or decisions based on these endpoints. Without both no effects level and the lowest observed 

effects level, it is impossible to determine is the response occurs over a wide or narrow range of 

values. This study is considered to be scientifically sounds and is classified as acceptable.

MRID 46020102 is a one generation reproductive toxicity test to groups (16 pens/ treatment 
45

level) of 1 male and 1 female, 27- week old norther bobwhite quail, assessed over approximately 

21 weeks. Ipconazole was administered to the birds in the diet at mean measured concentrations 

of <5 (LOD, negative control), 13.1, 22.4, 48.5, or 97.6 ppm ai. Nominal concentrations were 0, 

15, 25, 580 or 100 ppm. There were no significant treatment-related effects on adult mortality, 

clinical effects, body weights, food consumption, or necropsy findings at any test level. In 

addition, no treatment-related effects on egg production, fertility, embryonic development, or 

hatchability were observed at 13.1, 22.4, or 48.5 ppm ai levels. At the 97.6 ppm ai level, there 

were statistically significant reductions in hatchling survival ((16.3 hatchlings/pen versus 25.9 

hatchlings/pen in the control), and in the two percentage measurements using hatchling survival 

as the numerator. The percentage of hatchling survival/eggs set was 50.2% in the treatment and 

69.0% in the control. The percentage of hatchling survival # of hatchlings was 60.6% in the 

treatment and 89.5% in the control. Also at the 97.6 ppm treatment level, a reduction in the 

percentage of hatchlings/live embryos was significant. No treatment0related effect on egg shell 

thickness, or hatchling or 14-day old chick body weights were observed at any test level. 

LOAEC was 97.6 ppm ai and NOAEC is 48.5 ppm ai. This study is classified as scientifically 

sound and is considered to be acceptable. 

Mammalian toxicity data

There was no wild mammal data submitted or required for ipconazole. For the purpose of past 

and future assessments, risk to wild mammals is assessed based on the available mammalian 

toxicity studies conducted on laboratory mammals (both rats and mice). 

There were two acute oral studies available for mammals, one using a rat and a more sensitive 

toxicity test using a mouse. For MRID 45552701, an acute oral toxicity study used five male and 

five female mice orally dosed via metal stomach tube with doses of 300, 420, 600, 850 and 1200 

mg/kg ai. For dosage, the test material was suspended in olive oil with a constant dose volume of 

0.1 mL per 10 g of body weight. At 300 mg/kg there was no mortality. At 420 mg/kg one male 

and one female died. At 600 mg/kg 3 of the five males died and all five of the females died. 

Deaths occurred on days 2 and 4. At 300 mg/kg there were no symptoms. At 420 mg/kg 

symptoms were a decrease in locomotor activity, ptosis, lacrimation and (for one of the females 

and one of the males that died) lateral position. Additional sublethal effects observed at the 600 

mg/kg were ataxis gait and in females only, loose stool. Survivors had generally recovered by 

day 3. All mice dosed at 300 mg/kg had weight gains from day 0 to 3 and from day 3 to 7; with 

the exception of one female which experience slight weight loss. At higher doses, some surviving 

males lost weight between day 0 and day 3, but all survivors gained weight from day 0 to 14 and 

from day 7 to 14. Some mice which died had no abnormalities at gross necropsy. However, 

findings in others included a number of sublethal effects. Most mice surviving to test termination 

had no abnormalities, although some females experienced dilation of bursa in the ovaries. This 

study is considered acceptable. 

For MRID 4555270, an acute oral toxicity study used five male and give female rats orally dosed 

via metal stomach tube with doses of 300 (male only), 420 (male only), 600, 850, 1200, 1700, 

2400, and 3400 (male only) mg/kg. For dosage the test material was suspended in olive oil, with 

a constant dose volume of 1 mL per 100 g of body weight. At 300, 420 and 600 mg/kg there was 

no mortality. At 850 mg/kg, there were no mortalities among the males and three mortalities 
46

among the females. At 1200 mg/kg there were two male mortalities and four of the five females 

had died. At 1700 mg/kg four of the five males had died and the final female died. At higher 

doses, all males and females experienced complete mortality. Deaths occurred from day 1 to day 

6. At 300 mg/kg there were no sublethal effects. At 420 mg/kg one male showed reddish tears; at 

600 mg/kg there was a transient decrease in locomotor activity and loose stool, however 

symptoms were gone by day 3. Symptoms at higher dose levels included lateral position, loss of 

hair (generally starting around day 6 and persisting to the end of the observation period), reddish 

nasal discharge and top toe gait. All males dosed at 300, 420 and 600 mg/kg had body weight 

gains from days 0-3, 3-7, and 7-14. Two of the five dosed females dosed at 600 mg/kg 

experienced slight weight losses for day 0-3 but all had weight gains for days 3-7 and 7-14. 

Female survivors at 850 and 1200 mg/kg and male survivors at 1200 and 1700 mg/kg had initial 

weight losses day 0-3 but subsequent weight gains. Gross necropsy findings in rats which died 

included slight atrophy of the spleen and/or distention of the stomach. Sporadic findings at doses 

> 1200 mg/kg found severe stomach atrophy of the thymus, no stomach contents, thinning of the 

stomach wall, slight adhesion of the stomach and liver, sporadic perforation of the stomach, 

decrease in contents of the cecum. The only abnormality in rats surviving to test termination was 

the loss of hair on the back. This study is classified as acceptable. 

There are two studies available to evaluate the chronic exposure effects of ipconazole in 

mammals. These include a developmental study and a 2-generation study using rats. In the 

developmental toxicity study (MRID 45552710), ipconazole was administered to 24 rats via 

gavage at dose levels of 0, 3, 10, or 30 mg/kg-bw/day on days 6 through 15 of gestation. No 

treatment-related deaths of clinical signs of toxicity were observed in any animal. Body weight, 

body weight change and food consumption values for the low and mid-dose groups were similar 

to the control throughout the study. Overall weight gain by the high dose group was 71% of the 

control group level during the dosing interval. Food consumption by the high dose group was 

significantly less than that of the control group. The maternal toxicity LOAEC for ipconazole in 

rats is 30 mg/kg-bw/day based on decreased body weight gain and food consumption, and the 

maternal toxicity NOAEC is 10 mg/kg-bw/day. Male and female fetal body weights from the high 

dose group were significantly less than those in the control. No dose or treatment related 

external, visceral, or skeletal malformations were observed in any fetus from any group. 

However a significantly greater number of high-dose litters contained fetuses with visceral and 

skeletal variations compared to the control group. The major variations consisted of left umbilical 

artery, dilation of the renal pelvis and/or utterer and lumbar ribs; each of these occurred in the 

high dose group at significantly greater litter incidences compared to the controls. Thus the 

developmental LOAEC for ipconazole in rats is 30 mg/kg-bw/day based on decreased fetal body 

weight and increased incidences of visceral and skeletal variations. The developmental toxicity 

NOAEC is 10 mg/kg-bw/day. This study is classified as acceptable.

In the two generation reproductive toxicity study (MRID 47048914), ipconazole was 

administered in the diet to 32 rats at dietary levels of 0, 30, 100, or 300 ppm for 10 weeks prior to 

mating to produce the f1 litters. Upon weaning, the f1 parents were fed the test diets for 

approximately 10 weeks prior to mating to produce the f2 litters. There were no treatment related 

effects on mortality, clinical signs, body weights, or food conversion efficiency. Food 

consumption was decreased by 7-12% in the F1 males during pre-mating. In 300 ppm, P 

gestational body weight gains were decreased by 8% and food consumption was decreased by 5% 

during days 0-5; food consumption was decreased during lactations by 10-13%. The LOAEC for 
47

parental toxicity is 300 ppm (25.6/28.6 mg/kg-bw/day in males/females) based on decreased 

gestational body weight gains in the females, decreased food consumption in the male during premating and in the females during gestation and lactation, and increased relative organ weights. 

The NOAEC is 100 ppm (8.2/9.2 mg/kg-bw/day). There were no effects of treatment on the 

number of implantations, total or live litter size, post implantation survival, live birth, viability, or 

lactation indicies, sex ratio, clinical signs or sexual maturation. At 300 ppm, pup body weights 

were decreased in both generations by 6-15%. Overall body weight gains during lactations were 

also decreased in the F1 males and F2 males and females by 7-13%. Additionally at this dose, 

relative spleen weights were increased 10-12% in the F1 males and F2 pups. 7 of the 25 pups that 

died before test termination were observed to have thin build at necropsy compared to the 

controls. The LOAEC for offspring toxicity is 300 ppm based on the decreased pup body weight 

and body weight gains in both generations, increased relative spleen weights, and thin build. The 

NOAEC is 100 ppm. The LOAEC for reproductive toxicity was no observed. The NOAEC for 

reproductive toxicity is 300 ppm. This study is classified as acceptable. 
48

Appendix D. Comparison of Conazole Aquatic Toxicity Endpoints in ppm

Chemical 

name

PC Code

DP barcode 

reference for 

endpoints

Acute 

Freshwater 

Fish

Chronic 

Freshwater 

Fish

Acute 

Freshwater 

Invertebrates

Chronic 

Freshwater 

Invertebrates

Acute 

Estuarine/ 

marine Fish

Chronic 

Estuarine/ 

marine

Fish

Acute 

Estuarine/ 

marine 

Invertebrate

Chronic 

Estuarine/ 

marine 

Invertebrate

Vascular 

Aquatic Plant

Nonvascular 

Aquatic plant

Ipconazole

125618

LC50 = 1.53 

mg/L

NOAEC = 

0.18 mg/L

LC50 = 1.70 

mg/L

No data No data No data No data No data No data No data Rainbow trout Fathead minnow

Daphnia 

magna

45542237

Moderately 

toxic

47048902

--

45542235

Moderately 

toxic

Myclobutanil

128857

(D402503)

LC50 = 2.4 

mg/L

NOAEC = 

0.98 mg/L

EC50 = 11 

mg/L

No data

ACR 

calculated in 

assessment 

based on mysid 

shrimp data

LC50 = 4.7 

mg/L

No data

EC50 =0.24 

mg/L 0.0856 mg/L

No data

EC50 = 0.83 

mg/L

NOAEC = 

0.56

Bluegill 

Sunfish

Fathead 

Minnow

Daphnia 

magna

Sheepshead 

Minnow Mysid Shrimp Mysid Shrimp Selenastrum capicornutum

00144285

Moderately 

toxic

40480401

--

00141678

Slightly toxic

42747903

Moderately 

Toxic

42747902

Highly Toxic

47968901

--

41984801

--

Tetraconazole 

120603

(D380619)

LC50 = 3.85 

mg/L

NOAEC = 

0.30 mg/L

EC50 = 2.63 

mg/L

NOAEC = 

0.19 mg/L

LC50 >3.4 

mg/L

No data

ACR 

calculated in 

assessment 

based on 

freshwater fish 

data1

EC50 =0.44 

mg/L

No data

ACR 

calculated in 

assessment 

based on 

Dapnid data

EC50 = 0.31 

mg/L

NOAEC = 

0.032 mg/L

Bluegill No data

Sunfish

Fathead 

Minnow

Daphnia 

magna

Daphnia 

magna

Sheepshead 

minnow Mysid shrimp Duckweed

44367017

Moderately 

toxic

45823208

--

44267018

Moderately 

toxic

4852307

--

45823206

Moderately 

toxic

45823203

Highly toxic

45842201

--

Triticonazole

125620

(D389716)

LC50 >2.3 

mg/L

NOAEC = 

0.012

EC50 = 7.6 

mg/L

NOAEC < 

0.19 mg/L

LC50 >5.7 

mg/L

NOAEC = 

0.122

LC50 = 1.6 

mg/L

NOAEC = 

0.025

EC50 = 1.4 

mg/L

NOAEC = 

0.33 mg/L

EC50 = 0.35 

mg/L

NOAEC = 

0.033 mg/L

Rainbow Trout Fathead 

Minnow

Daphnia 

magna

Daphnia 

magna

Sheepshead 

minnow

Sheepshead 

minnow Mysid shrimp Mysid shrimp Duckweed Skeletonema costatum

44802020

Moderately 

toxic

47622101

--

44802021

Moderately 

toxic

46876701

--

44802023

Moderately 

toxic

46876702

--

44922304

Moderately 

toxic

46876703

--

44802119

--

44802121

--
49

Chemical 

name

PC Code

DP barcode 

reference for 

endpoints

Acute 

Freshwater 

Fish

Chronic 

Freshwater 

Fish

Acute 

Freshwater 

Invertebrates

Chronic 

Freshwater 

Invertebrates

Acute 

Estuarine/ 

marine Fish

Chronic 

Estuarine/ 

marine

Fish

Acute 

Estuarine/ 

marine 

Invertebrate

Chronic 

Estuarine/ 

marine 

Invertebrate

Vascular 

Aquatic Plant

Nonvascular 

Aquatic plant

Cyproconazole

128993

(2011 New 

Use)

LC50 = 19.0 

mg/L

NOAEC = 

0.161 mg/L

LC50 = 26.0 

mg/L

NOAEC = 

0.019 mg/L

LC50 = 21.0 

mg/L No data

ACR 

calculated in 

assessment 

based on 

freshwater fish

EC50 = 2.6 

mg/L

No data

ACR

calculated in 

assessment 

based on 

Daphnid and 

Mysid data

EC50 = 0.094 

mg/L

NOAEC = 

0.0245 mg/L

EC50 = 0.026 

mg/L

NOAEC = 

0.0059 mg/L

Rainbow trout Rainbow Trout Daphnia 

magna

Daphnia 

magna

Sheepshead 

Minnow Eastern Oyster

40607733

Moderately 

toxic

46950008

--

40607735

Slightly toxic

47036201

--

43187704

Slightly toxic

43187702

Moderately 

toxic

47067101

--

42656401

--

Difenoconazol

e

128847

(D377719)

LC50 = 0.810 

mg/L

NOAEC = 

0.0087 mg/L

EC50 = 0.770 

mg/L

NOAEC = 

0.0056 mg/L LC50 = 0.819

No data

LC50 = 0.150 

mg/L

NOAEC < 

0.000115 mg/L

EC50 = 1.9 

mg/L

EC50 = 0.098 

mg/L

Rainbow Trout Fathead 

Minnow

Daphnia 

magna

Daphnia 

magna

Sheepshead 

Minnow Mysid shrimp Mysid Shrimp Duckweed Navicula pelliculosa

42245107

Highly toxic

42245115

--

42245110

Highly toxic

42245114

--

42245112

Highly toxic

42245111

Highly toxic

46950133

--

46920504

--

46920508

--

Fenbuconazole

129011

(D345899)

LC50 = 0.68 

mg/L

NOAEC = 

0.027 mg/L

EC50 = 2.30 

mg/L

NOAEC = 

0.078 mg/L

LC50 = 1.8 

mg/L

No data

ACR 

calculated in 

assessment 

based on 

freshwater 

fish1

LC50 = 0.63 

mg/L

No data

ACR 

calculated 

based on data 

from mysid 

shrimp

No data

EC50 = 0.25 

mg/L

NOAEC = 

0.125 mg/L

Bluegill 

Sunfish

Fathead 

Minnow

Daphnia 

magna

Daphnia 

magna

Sheepshead 

minnow Mysid shrimp Scenedesmus subspicatus

41073506

Highly toxic

44215801

--

41073507

Moderately 

toxic

41875007

--

43058001

Moderately 

toxic

43058002

Highly toxic

42914702

--

Propiconazole

122101

(D429077)

LC50 = 0.850 

mg/L

NOAEC = 

0.095 mg/L

EC50 = 1.3 

mg/L

NOAEC = 

0.180 mg/L

LC50 = 2.244 

mg/L

No data

EC50 = 0.510 

mg/L

NOAEC = 

0.205 mg/L

EC50 = 3.5 

mg/L

EC05 = 0.380 

mg/L

EC50 = 0.021 

mg/L

EC05 = 0.015 

mg/L

Rainbow trout Fathead 

Minnow

Daphnia 

magna

Daphnia 

magna Spot Mysid shrimp Mysid shrimp Duckweed Skeletonema costatum

0067923

Highly toxic

133364

--

132932

Moderately 

toxic

49300501

--

132921

Moderately 

toxic

260201

Highly toxic

133365

--

133363

--

132939

--
50

Chemical 

name

PC Code

DP barcode 

reference for 

endpoints

Acute 

Freshwater 

Fish

Chronic 

Freshwater 

Fish

Acute 

Freshwater 

Invertebrates

Chronic 

Freshwater 

Invertebrates

Acute 

Estuarine/ 

marine Fish

Chronic 

Estuarine/ 

marine

Fish

Acute 

Estuarine/ 

marine 

Invertebrate

Chronic 

Estuarine/ 

marine 

Invertebrate

Vascular 

Aquatic Plant

Nonvascular 

Aquatic plant

Prothioconazol

e

113961

(D363044)

LC50 = 1.69 

mg/L

NOAEC = 

0.148 mg/L*

EC50 = 1.2 

mg/L

NOAEC = 

0.103 mg/L*

LC50 >10.3 

mg/L

No data

EC50 = 0.060 

mg/L*

NOAEC = 

0.064 mg/L*

EC50 = 0.035 

mg/L

NOAEC = 

0.0058 mg/L*

EC50 = 0.021 

mg/L

NOAEC = 

0.0073 mg/L

Rainbow Trout Fathead 

Minnow

Daphnia 

magna

Daphnia 

magna

Sheepshead 

minnow Mysid shrimp Mysid shrimp Duckweed Skeletonema costatum

46246019

Moderately 

toxic

46246033

--

46246009

Moderately 

toxic

46246029

--

46246027

Slightly toxic

46246017

Very Highly 

toxic

4624630

--

46246104

-- 46246110

Tebuconazole

128997

(D362764)

LC50 = 2.27 

mg/L

NOAEC = 

0.012 mg/L

EC50 = 2.88 

mg/L

NOAEC = 

0.120 mg/L

LC50 = 5.9 

mg/L

NOAEC = 

0.0219 mg/L

EC50 = 0.490 

mg/L

NOAEC = 

0.035 mg/L

EC50 = 0.1515 

mg/L

NOAEC = 

0.0342 mg/L

EC50 = 1.45 

mg/L

NOAEC = 

0.320 mg/L

Rainbow Trout Rainbow trout Daphnia 

magna

Daphnia 

magna

Sheepshead 

minnow

Sheepshead 

minnow Mysid shrimp Mysid shrimp Duck weed Scenedesmus subspicatus

46919204

Moderately 

toxic

40700914

--

46919205

Moderately 

toxic

40700915

--

40995903

Moderately 

toxic

420382202

--

40995902

Highly toxic

42039201

--

44246901

--

40995908

--