### UNITED STATES ENVIRONMENTAL PROTECTION
AGENCY



### MEMORANDUM OFF I CE OF CHEM I CA L SAFETY

A N D POLLUTIO N P R EVE N TIO N



### PC Code: 125618

DP Barcode: 0428127

Date: December 9
, 2015

SUBJECT : EFED Registration Review Problem Fomrn l ation for Ipcona zo le



### FROM:

TO:



### REVIEWED BY:

THROUGH: 

## . t>/10/15

Hannah Yingling

,

# Biologist~~~~ Mohammed Ruhman

, Ph.D.

, Senior

## Agronomi**~** \.

E nvironmental Risk Branch 5

## ~ · 

# IJ../fo/15

Environmental Fate and Effec ts Division (7507P)

Brittan y Pruitt, Chemical Review Manager

Trac y Perry

, Team Leader

Risk Management and Impl ementation Branch 3

Pesticide Re-Evaluation Di vision ( 7508P)

A ll en Vaughan

, Entomologist

Gabe Rothman

, Environmental Scientist

Env ironm ental Risk Branch 5

Environmental Fate and Effects Division (7507P)

Mah Sham im

, Branch Chief

Environmenta l Risk Branch 5

Environmenta l Fate and Effects Division (7507P)

The Env ironm enta l Fate and Effects Division (EFED) has completed the attached preliminary problem fo rmulati on for the ecolog i cal ri s k

, env ir onmental fate, endangered species

, and drinking

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

### 2 OFFICE O F CHEMICAL SAFETY

AND POLLUTION PREVENTION 

### UNITED STATES ENVIRONMENTAL PROTECTION
AGENCY



## EFED Registration Review Problem Formulation for Ipconazole

Ipconazole : 2

- [(4

- Chlorophenyl) m ethyl]

- 5

- (1

- methylethyl)

- 1

- (1 H

- 1, 2, 4triazol

- 1

- y1 metyl) cyclopentano l;
CAS No. : 1 25225

- 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 Conte nts

1. Executive summary

................................ ................................ ................................ ................. 4

A. Environmental Fate Data Gaps

................................ ................................ .......................... 4

B. Ecologic al 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 Scree ning 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 summar y

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 ipcon a z ole. This document pr ovides an overview of the environmental fate, ecological effects, potential risks associated with its use s and the uncertainties which currently exist relevant

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

w ould 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 requeste d:

(1) One aerobic soil study ( OCSPP 835.4100 ) for one soil ob tained from are as 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 i dentifying if isomers are biologically active and if they differ in toxicity; (2) One ad s o r ption/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 r egistrant 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) ECM s and associated ILVs ( OCSPP 850.6 100 ) for soil/sediment and water ; (5) F ish bio

- concentration : No 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

.



## B. **Ecological Effects Data Gaps**

The eco logical 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) Acut e 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 non vascular 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

- g uideline) (17) Pollinator feeding/semi

- field study

- The need for these studies is contingent upon the

results of lower tier bee studies (Non

- guideline) (18) P ollen 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 t he 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 s uch 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 possib ility. 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 mixt ure 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.

T he 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 termi nology 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 uncertaint y associated with already submitted environmental fate studies (all submitted studies):

“ Studies were conducted using an isom er mixture similar to that stated for the active ingredient of the pesticide (9:1)” (5) Clarify t he 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 s uch 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 i t is registered for seed treatment in many crops. The crops include b uckwheat, canola r ape & m ustard, c onifers, c orn (field, pop & sweet) , m illet

,

o rnamental flowers, p eanuts, s orghum, s oybeans, s unflower, t urf grass, some cereal grains ( w h eat, barley, oa ts, rye & t riticale) and crop groups including: beans and p eas, v egetables ( Brassica “c ole ” leafy, c ucurbits, l eafy except Brassica

, l egumes, and some root & t uber) and

f

orage and s ilage of corn, millet, rye, triticale, sorghum, wheat, barley and oats

.

E FED 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 Re view. Recent ecological risk

assessments for ipconazole include d : the 200 7 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 ipconazole 1 

### formulated as liquid and liquid suspension. The chemical is sole ly used as a see d treatment for many crop and crop groups ( Table 1 a , 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 th e insecticides i midacloprid and clothianidin ( Table 1 a , 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 I pconazole /T hiram
10/350 FS Pinnacle Summit

EPA Registration Number 400

- 544 400

- 546 400

- 547 400

- 566 400

- 570
Label Stamp Date (m onth

- y ear ) 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 Summ it

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 Us e 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 U se

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 2.49 E

- 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 Veg etables: 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 A pex: 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 Regis tration 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 Product s 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 (m onth

- y ear ) 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

C orn ( 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 U se 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.

C ompany 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 (m onth

- y ear ) 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 N o 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 a nd oats 

### Use patterns for crop groups are listed in Table 2 include: beans and p eas 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 & Pea s 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/T uber 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 sp inach, 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), dandel ion, 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, c itron 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 addit ion 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 th e 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. seed s

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 V egetables: 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) M illet, Rye & Triticale 2.47E

- 03 Soybeans 2.50E

- 03

Sunflower 2.50E

- 03 (3) Sorghum 5.01E

- 03
Turf grass 2.50E

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

- 03 Wheat, Barley, Oats, Rye &

Triticale 2.51E

- 03



### Ecological and drinking water maximum exp osure concentrations for surface water are expected to depend mainly on chosen representative scenario s , the maximum l abel 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 am ount of seeds needed to seed an acre of the crop in question (seeding rate)

. S eeding depth is also dependent mainly on the crop (c an be obtained ) and other factors that are difficult to determine such as the depth where moisture is available for seed growt h (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 si mulated 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 ch oice are

detailed elsewhere 3 

### . 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 assume s that “ Crops are to be seeded at appropr iate depths and No broadcast seeding is allowed for treated

seeds ” . The registrant is requested to include th is 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 sugge sts 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 asses ed 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 invertebrate s were in ppm ranges and were several orders of magnitude greater than the EECs (which are measured in ppb). Therefore, no RQ values exceeded th e 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 Rate s of Crops Grown in the United S tates

. BEAD report, EPA.

3 Refer to the 2 nd drink ing 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’ le vel of concern.

The most sensitive acute toxicity endpoint for birds (LD 50 

### = 962 ppm) and mammals (LD 50 

### = 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 mam malian 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

In verts Aquatic

Plants Groundwater

Contamination Persistence Degradates

of Concern

Yes 1 Yes 2 Yes 3 Yes 4 Yes 5 Refer to 6 Yes 7 Yes 8 Yes 9 Yes No 10

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 B CF study was submitted.

7 N o 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 acu te 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 app ears to overcome it expected lo w mobility (Average Koc= 2,428 Kg L

- 1);

10 This decision is b ased on current fate data which indicates parent is applied at low rate, highly persistence and the degradate 1, 2, 4

t riazole (a common degradate of the conazoles 4 pesticides) formed at low conc entration 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 water 5



### . The 1 st 

### assessment was based on use as p er

4 Refer t o 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 (P C Codes: 600074

– 1, 2, 4

- Triazole; 600011

– Triazole Alanine; 600082

– Triazole Acetic Acid. DP Number: D320682; Dated Feb 28, 2006.

5 1 st assessment: Addendum: Tier 1 Drinking Water Concentrations for Seed Treatment Uses of Ipconazole; EFED

Memorandum da ted March 15, 2004; DP Barcode: D289658; and;

2 nd 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 2 nd 

### assessment was based on additional new use patterns as per

additional t hree labels. In these assessments, t he driver for the EDWCs, for surface and ground water, was seed treatment on potato which was not intended to be included in the label s 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 patter ns 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 non

registered 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 ex posure.

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 f or ipconazole. Futu re assessments will not probably change as it will be based on pa rent ipconazole alone because : (1) ipconazole is highly persistent ( 90 th 

### 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 t riazole which was found, in only one aero bic soil metabolism study, at relatively low concentrations (maximum

concentration= 1 2 % 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 EDWC s 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 con azole 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 o n the labeled use patterns is requested. Future estimation of the drinking water exposure will take in to consideration data obtained from requested studies and will use official models at that time. In this respect, it is noted that current

surface water e xposure 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 w ater 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_3 03d?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 Sub group 6C to the Entire Crop Group 6 for Use in Human Health Risk Assessment.

### 14 Furthermore, no Total Maximum Daily Load (TMDL) criteria have be en 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 d ata 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 EC 50 or LC 50 in a standardized test usually with midge, scud, or daphnids; LOC= 0.5.



## 5. Environmental Fate and Transport

In most cases, f ate 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 soi l 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 p hysical/ chemical properties and abiotic trans formation are summarized in Table 6

Table 6. Physical/ chemical and abiotic properties of ipconazole

Parameter Value 1 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 Value 1 Reference MRID (Classification)

And Notes ) 2

Vapor Pressure (2 5 °C) cc

- isomer: 1.6 x 10

- 8 torr

ct

- isomer: 4.5 x 10

- 9 torr Registr ant data ; Limited volatility from dry surfaces

Henry's Law Constant ( 25 °C; Calculated) cc

- isomer: 1. 04 x 10

- 9 atm.m 3 mole

- 1

ct

- isomer: 5.2 x 10

- 1 1 atm.m 3 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 fis h

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



### Based on data presented in Table 6 , i pconazole 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 order s 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 relativel y high log Kow of the isomer mixture ( 4.21) although the value for one of the isomers, the ct

isomer is less ( 3.8 ). No bioaccumulation test was subm itted in order to determine bio

concentration factors / depuratio n to check on conclusions drawn from values r eported for the

O ctanol/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

h ydroxyl

- derivative of ipconazole and hydroxyl

- derivative i somer (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 summarize d 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
@ 2 5 °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 90 th percentile half

- life (n=2)

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

CO 2 : 1% at EOS 455422

- 24 ( S ) for

the 1 st soil

And

460084

- 02 (A)

for the 2 nd soil ;

Only two soil s

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, 8 1 3 L Kg

- 1 for Mutchler sandy loam soil from

ND (pH 5.9 , O.C 1.6% and CEC= 21 meq/100 ); and 2,4 10 L Kg

- 1 for a n 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: 2,4 31 L Kg

- 1 (n= 6 ) 455422

- 25 (S)
and

468275

- 03 (A)

Based on the

a verage 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) 45 5422

- 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 CO 2 = 0.2%
Terrestrial Field Dissipation t

1⁄2 S tudies 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). Long

term use in the same field may result in an accumulation of active in gredient. However, due to the low application rates, the long term concentration level of the chemical is expected to be low.

A ccumulation can be estimated based on applying the chemical, with seeds, yearly at a rate representing the maximum application ra te 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 th e first year concentration in 20 years based on yearly applications (repeated yearly seeding with treated seeds) and the chemical 90 th 

### percentile half

- life of 2,483 days.

Figure 1 Expected ipconazole accumulation in the soil as a result of repeated seedi ng 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 20EECs 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]2 CC3=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 i somers 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 T able 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 i pconazole

.



## 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) LC 50 = 1.53

NOAEC = 0.34 45542237 Moderately

Toxic Supplemental

Bluegill

Sunfish ( Lepomis macrochirus) LC 50 >0.73

NOAEC = 0.73 45542236

NA Supplemental

850.1400 Chronic
Freshwater Fish Fathead
Minnow NOA EC = 0.18

ppm 47048902 (47104001)

NA Acceptable

850.1010 Acute Freshwater

Invertebrates Daphnid LC 50 = 1.70 ppm 45542235 Moderately

Toxic Acceptable

850.1075 Acute
estuarine/marine

fish No data submitted

850.1400 Chronic

estuarine/marine

fish No data su bmitted

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 s tudies, 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 Toxici ty Endpoint Study MRID and Toxicity
Classification Acceptability

850.2100 Avian Acute Oral Bobwhite quail LD 50 = 962 ppm 4554223 2 Slightly toxic Acceptable

850.2200 Avian Dietary Bobwhite quail LC 50 > 5710 ppm NOAEC < 169 ppm 45542234 Practically nontoxi c Supplemental

Mallard LC 50 > 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 Mou se LD 50 = 537 mg/kg

bw/day (males) 45552701 Moderately Toxic Acceptable

Rat LD 50 = 1338mg/kg

bw/day (males) 45552702 Moderately Toxic Acceptable

-- Developmental Toxicity Rat NOAEC = 10 mg/kg

bw/day LOAEC = 30 mg/kg

bw/day 45552710 Acceptable

Reprod uctive 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
Gui deline P ollen 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 pestici des 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 a c c or d ing to the certainty that the incident results from pestici de 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 p reliminary review on September 8, 201 5 of EIIS did not return any incidents associated with ipconazole use. Additionally, T he Aggregate Incident Report for EFED did not return any minor fish, plant or wildlife incidents; t here were no avian incidents r eported from AIMS.



## 7. Exposure Pathways of Concern

As a seed

- treatment fungicide, ingestion of treated seed placed in soil and s eed dropped on soil surface at the time of planting is the primary pathway through which exposure may occur for

terrestrial wi ldlife. 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 s uch 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 ve rsus 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 wat er 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 i s 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

. Out put from models can be

found in Appendix B an d 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 cur rently 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 descr ibed 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 e stimated environmental concentrations (EECs) generated using the Surface Water Concentration Calculator (SWCC) model to simulate a waterbody that is considered representative of vulnerable aquatic environmen t ( e.g. , ponds and

streams in headwater watershe ds). Currently, t errestrial 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 a ll 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

Environme ntal 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**

Toxi city data presented in Table 8 and Table 9 of thi s 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 li terature studies are identified using EPA’s EC OTOXicology 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

p rovide 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 A ssessments

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 A pproaches 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 r eport 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 conc erns 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 as sessment 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 registra tion 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 th e 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, the se methods will be applied to subsequent analyses of ipconazole as part of completing this registration review.



## 10. E ndocrine Disruptor Screening Program

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

EDSP tes ting

. F or 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 inadequaci es:

(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 ad s o rption/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 th is study is required for modeling. In absence of th is stud y 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 1 1 identif ies environmental fate studies by MRID that offer data for each guideline requirement, a s well as study classifications and requested data

. In addition, r equested data needed to support the future risk assessment are listed in details earlier in t he 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

- 2 2 Acceptable

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

835.4100 Aerobic soil metabolism 1 st study: 460084

- 02;

2 nd study: 455422

- 24 1 st study: Acceptable;

2 nd 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 & leaching 1 1 st st udy: 468275

- 03 ; 2 nd study: 455422

- 25 ; Leaching: 455422

- 26 1 st study: Acceptable

2 nd 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 Che mistry 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 simil ar to that

stated for the active ingredient of the pe sticide



## B. **Ecological Effects** 

Table 1 2 and Table 1 3 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. Ratio nale 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 specie s. For ip conazole, 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 w ere 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 conaz oles 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), t wo 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

. T wo 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 LC 50 

### = 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 f or 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 lifecy cle 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

cu rrently 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, EC 50 

### = 0.06 0 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 4687670 3)

. 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 Submitte d 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 Freshw ater
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 Freshw ater fish acute toxicity 45542237 Supplemental Yes A cute 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 A cute 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

chemi cal class. The most sensitive endpoint available for the given taxa will be used for assessment purposes.

### 29 Table 12 Submitte d 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

inad equate 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 calculat ed 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

K
oc of the chemical.

850.1400 Freshwater fish early

- life stage 47048902 Acceptable Yes Freshwater fish early

- life stage data us ing

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 regis trant 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 Submitte d 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

subm itted 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 wi ll 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 conazol e 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
Classi fications 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, a cute oral toxicity d ata 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 spe cies ( 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 in dicators 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

850.23 00 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 treatmen t 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

toxi city 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/semi

field (Tier II) No data

submitted NA Need for

data contingent

upon results of
Tie r I bee
studies

Non
Guideline P o llen 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 continge nt

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. R eferences

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 Refe rence

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

- wat er

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 A erobic 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

N orth 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. [ 14 

### C]

- Ipconazole: adsorption/desorption to a loamy sand (batch equilibrium method). Unpub lished 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 initiat ed 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

- 31 7 (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 Kouchi

Soil: Ipconazole Technical: Lab Project Number: 40. Unpublished st udy 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 Tox icity 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 Die tary 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 (40 0

- 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 Flow

Through 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 Flow

Through Acute Toxicity Test with the Rainbow Trout (Oncorhynchus mykiss):

### 36 Final Report: Lab Project Number: 117A

- 118. Unpublished study prepared by
Wildl ife 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 Crom pton 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 Flow

Through Acute Toxici ty 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

47048 901 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 Dat a 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 C rompton 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):
C rompton 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 Registran t

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 Friedlan der, 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 C o./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 25 o C; mg/L) 6.9

Mammalian LD 50 (mg/kg

- bw) 537
Mammalian test species other
Body weight (g) of "ot her" mammalian species 25

Mammalian NOAEL (mg/kg

- bw) 8.2
Mammalian test species laboratory rat
Body weight (g) of "other" mammalian species

Avian LD 50 (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) f or 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 potenti al
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 co ntribute 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 poten tial

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 LD 50 (mg/kg bw) 2150
Enter Mineau Scaling Factor 1.15
Enter Tested Bird Weight (kg) 0.178

**Mammal**

Enter Lowest Rat Oral LD 50 (mg/kg bw) 5000

Enter Lowest Rat Inhalation LC 50 (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/m 3 ) 1.86E

- 02

Maximum 1

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

- 03

Adjusted Inhalation LD 50 4.65E+00

Ratio o f Vapor Dose to Adjusted Inhalation LD 50 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 LD 50 9.09E

- 02 Exposure not Likely Significant

Results Mammalian (0.015 kg )

Maximum Vapor Concentration in Air at Saturation (mg/m 3 ) 1.86E

- 02

Maximum 1

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

- 03

Adjusted Inhalation LD 50 1.15E+02

Ratio of Vapor Dose to Adjusted Inhalation LD 50 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 LD 50 4.60E

- 03 Exposure not Likely Significant

### 41 

## Appendix C . Full Study Details for all Toxicity St udies

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 ( Oncorhynchu s 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; c ontrols), 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 ca tegorizes 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 on ly one partial kill, thus a precise 96

- hour LC 50 

### 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 455422 36 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 tre atment 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

LC 50 

### lower than the LOAEC. Thus t he LC 50 

### 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 LC 50 

### exceeds 1 ppm. Sublethal

effects wer e 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 mo rtality 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 LC 50 

### cannot be determined. Be cause the two kills produced were 80% and 100%,

the calculated LC 50 

### 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 w ould 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

min now 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 s olvent 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 a i/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 l evels, 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 corresp onding 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 canno t 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 Toxic ity 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 t est 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, morta lity 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 LC 50 

### was 1.70 ppm ai (95% C.I. 1.23

- 2.63 ppm) which categorizes ipconazole as moderately toxic to Daph nia 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 470 4 8901) 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 be tween 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 s tudy (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 vi rginianus). 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 100 0 mg/kg test level and 90% in the 2000 mg/kg

- bw test level. The acute LD 50 

### 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 obser ved 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 w as 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 female s 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 2 50 mg/kg for females. Necropsy of decedent birds revealed a thin or emaciated body condition with a loss of muscle mass an d prominent keel, discoloration of the spleen, pale kidneys, empty crop, congested capillaries in the crop and in several cases, a fl accid 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 t he 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 bo bwhite (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, 1 760, 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

- respon se curve, and a reliable LC 50 

### cannot be calculated from the study data. The estimated LC 50 

### exceeds the highest test concentrations, 5710 ppm ai. Guideline criteria require <20% kill at 5000 ppm ai to classify a compound as having an LC 50 

### > 5000 ppm ai. T he estimated LC 50 

### 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 l evels, 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. Concentration

responsive reductions in body weight changes were observe d 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 gr oup 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 avo idance of contaminated food is unknown. Because the test did not produce a definitive LC 50 

### , 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 ob served during the study. The 8

- day acute dietary LC 50 

### 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

- respo nsive 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 tr eatment 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 stud y 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 appro ximately 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 tre atment

- 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 observ ed 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 hatchli ng 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 p pm 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 NOA EC 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. F or 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 sym ptoms. 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 o nly, 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 l ost 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 survivi ng 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 met al 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 ther e 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 per iod), 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,

decrea se 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 o f 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 weig ht 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 variatio ns 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 ipconaz ole 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 reproduc tive 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 approximat ely 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/fem ales) based on decreased gestational body weight gains in the females, decreased food consumption in the male during pre

mating 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

we re 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 

## A ppendix D . Comparison of Co nazol e A quatic T oxicity E ndpoints 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/

mar ine

Fish Acu te
Estuarine/

marine

Invertebrat e Chronic
Estuarine/

marine

Inver t ebrate Vascular Aquatic Plant Nonvascular Aquatic plant

Ipconazole

125618 LC 50 = 1.53 mg/L NOAEC = 0.18 mg/L LC 50 = 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) LC 50 = 2.4 mg/L NOAEC = 0.98 mg/L EC 50 = 11 mg/L No data

ACR

calculated in

assessment
based on mysid

shrimp data LC 50 = 4.7 mg/L

No data EC 50 =0.24 mg/L 0.0856 mg/L

No data EC 50 = 0.83 mg/L

NOAEC =

0.56 Bluegill

Sunfish Fathead

Minnow Daphnia

magna Sheepshead

Minnow Mysid Shrimp Mysid Shrimp Selenastrum capicornutum

00144285 Moderately

tox ic 40480401

-- 00141678 Slightly toxic 42747903 Moderately

Toxic 42747902 Highly Toxic 47968901

-- 41984801

--

Tetraconazole

120603

(D380619) LC 50 = 3.85 mg/L NOAEC = 0.30 mg/L EC 50 = 2.63 mg/L NOAEC = 0.19 mg/L LC 50 >3.4 mg/L No data

ACR

calculated in

assessment
based on

freshwater fish

data 1 EC 50 =0.44 mg/L No data

ACR

calculated in

assessment
based on Dapnid data EC 50 = 0.31 mg/L

NOAEC = 0.032 mg/L

No data Bluegill

Sunfish Fathead

Minnow Daphnia

magna Daphnia

magna Sheepshead

minnow Mysid shrim p Duckweed

44367017 Moderately

toxic 45823208

-- 44267018 Moderately

toxic 4852307

-- 45823206 Moderately

toxic 45823203 Highly toxic 45842201

--

Triticonazole

125620

(D 389716 ) LC 50 >2.3 mg/L NOAEC =

0.012 EC 50 = 7.6 mg/L NOAEC < 0.19 mg/L LC 50 >5 .7 mg/L NOAEC =

0.122 LC 50 = 1.6 mg/L NOAEC =

0.025 EC 50 = 1.4 mg/L

NOAEC = 0.33 mg/L EC 50 = 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 Skel etonema

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 A cute
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

Inver t ebrate Vascular Aq uatic Plant Nonvascular Aquatic plant

Cyproconazole

128993

(2011 New Use) LC 50 = 19.0 mg/L NOAEC = 0.161 mg/L LC 50 = 26.0 mg/L NOAEC = 0.019 mg/L LC 50 = 21.0 mg/L No data

ACR

calculated in

assessment
based on

freshwater fish EC 50 = 2.6 mg/L No data

ACR

calculated in

assessment
based on Daphnid and Mysid data EC 50 = 0.094 mg/L

NOAEC = 0.0245 mg/L EC 50 = 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) LC 50 = 0.810 mg/L NOAEC = 0.0087 mg/L EC 50 = 0.770 mg/L NOAEC = 0.0056 mg/L LC 50 = 0.819

No data LC 50 = 0.150 mg/L NOAEC < 0.000115 mg/L EC 50 = 1.9 mg/L EC 50 = 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

Hi ghly toxic 42245114

-- 42245112 Highly toxic 42245111 Highly toxic 46950133

-- 46920504

-- 46920508

--

Fenbuconazole

129011

(D345899) LC 50 = 0.68 mg/L NOAEC = 0.027 mg/L EC 50 = 2.30 mg/L NOAEC = 0.078 mg/L LC 50 = 1.8 mg/L No data

ACR

calculated in

asse ssment
based on

freshwater

fish 1 LC 50 = 0.63 mg/L No data

ACR

calculated

based on data from mysid

shrimp No data EC 50 = 0.25 mg/L

NOAEC = 0.125 mg/L Bluegill

Sunfish Fathead

Minnow Daphnia

magna Daphnia

magna Sheepshead

minnow Mysid shrimp Scenedesm us subspicatus

41073506 Highly toxic 44215801

-- 41073507 Moderately

toxic 41875007

-- 43058001 Moderately

toxic 43058002 Highly toxic 42914702

--

Propiconazole

122101

(D429077) LC 50 = 0.850 mg/L NOAEC = 0.095 mg/L EC 50 = 1.3 mg/L NOAEC = 0.180 mg/ L LC 50 = 2.244 mg/L

No data EC 50 = 0.510 mg/L NOAEC = 0.205 mg/L EC 50 = 3.5 mg/L

EC 05 = 0.380 mg/L EC 50 = 0.021 mg/L

EC 05 = 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 Ac ute
Freshwater

Invertebrates Chronic

Freshwater

Invertebrates Acute
Estuarine/
marine Fish Chronic
Estuarine/

marine

Fish Acute
Estuarine/

marine

Invertebrate Chronic
Estuarine/

marine

Inver t ebrate Vascular Aquatic Plant Nonvascular Aquatic plant

Prothioc onazol

e 113961

(D363044) LC 50 = 1.69 mg/L NOAEC = 0.148 mg/L* EC 50 = 1.2 mg/L NOAEC = 0.103 mg/L* LC 50 >10.3 mg/L

No data EC 50 = 0.060 mg/L* NOAEC = 0.064 mg/L* EC 50 = 0.035 mg/L

NOAEC = 0.0058 mg/L* EC 50 = 0.021 mg/L

NOAEC = 0.0073 mg/L

Rainbow Trout F athead

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) LC 50 = 2.27 mg/L NOAEC = 0.012 mg/L EC 50 = 2.88 mg/L NOAEC = 0.120 mg/L LC 50 = 5.9 mg/L NOAEC = 0.0219 mg/L EC 50 = 0.490 mg/L NOAEC = 0.035 mg/L EC 50 = 0.1515 mg/L

NOAEC = 0.0342 mg/L EC 50 = 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

-- 4 0995903 Moderately

toxic 420382202

-- 40995902 Highly toxic 42039201

-- 44246901

-- 40995908

--