### UN I TE D STATES ENV IR ONMENTAL P R OTECTION AGENCY
W AS H I NGT O N

. D C 20460

OFF I CE OF C H EMICA l SAFFTY AND PO LL UTION P R r VENT I ON



### PC Codes: 128922 

## + 128923 

### DP Barcode: D415245 Date: March 19 ,2 014



### MEMORANDUM

Subject:



### To:

From: Registra t i on Review Problem Formulation for Imazethap yr and Imaze thapyr Ammonium Salt

Kather i n e S t. Clair, Chemical Review Manager Kevin Cos te ll o, Branch Chief Risk M anagement and Impl ementation Branch II Pesticide Re-evaluation Division (7508 P)

Edwar d Odenkirchen, Ph.D., Senior Sc ient

. ist 

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# \**~** Stephe n Wente, Ph.D., Biolo gist 

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## 3 \.Ci. 1 \ 

### Suj atha Sa nkula, Ph.D., Branch Chief _; 

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### Environmental Risk Bran ch 1 Environmental Fate and Effects Division (7507 P ) 

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Office of P estic ide Programs .:>

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### The Environmental F a te and Effects Di vision (EFED) has completed the problem formulation (attached) for the environmental fate, ecological risk

, endange red species, and drinking water
exposure assessments to be conducted as part of the Registration Review of the herbicide imazethapyr and its ammonium salt. Functioning as the first stage of the risk assessme nt process for registration**revie~ ,**  

### this problem formulation provides an overview of what is currently known about the environmental fate and ecological effects associated with imazethapyr (acid and ammonium salt) and de gradates. It 

### describes the preliminary ecological risk hypothesis and analysis plan for eva l uat ing and characterizing drinking water exposure and risk to non-target species and the environment in support of the Registration Review of imazethapyr. This document also recommends st udie s that should be included in a data call-in (DC I ) to address uncertainties surrounding the environmental fate and potential ecological effects of imazethapyr.



### 1

### 2 

# REGISTRATION REVIEW

PROBLEM FORMULATION

I mazethapyr and the A mmonium S alt of Imazethapyr

N N N COOH

O 

### Imazethapyr

N N N COO

- + NH 4 +

O 

### Ammonium Salt of Imazethapyr

CAS Numbers: 81335

- 77

- 5 (imazethapyr) and 101917

- 66

- 2 (ammonium salt of imazethapyr)

US EPA PC Codes: 128922 (imazethapyr) and 128923 (ammonium salt of imazethapyr)

Prepared by: Edward Odenkirchen , Ph.D., Senior Scientist Stephen Wente, Ph.D., Biologist Environmental Risk Branch I

Reviewed by: Faruque Khan, Ph.D., Senior Fate Scientist Robin Sternberg, Ph.D., Wildlife Biologi st Environmental Risk Branch 1 Michael Wagman, Biologist Environmental Risk Branch 6 James Carleton, Ph.D., Fate Scientist Environmental Risk Branch 4 Environmental Fate and Effects Division U. S. Environmental Protection Agency Office of Pesticide Programs Environmental Fate and Effects Division Environmental Risk Branch I 1200 Pennsylvania Ave., NW Mail Code 7507P Washington, DC 20460

### 3 

## Contents

1. Executive summary

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

1 Introduction

................................ ................................ ................................ ............................. 5

2 Previous Asses sments

................................ ................................ ................................ ............. 6

2.1 Ecological Risk Assessments

................................ ................................ ........................... 6

2.2 Drinking Water Assessments

................................ ................................ ........................... 7

2. 3 Clean Water Act Programs

................................ ................................ ............................... 7

3 Overview of Imazethapyr Use

................................ ................................ ................................ 7

4 Environmental Fate Summary

................................ ................................ .............................. 10

5 Ecological Effects Summary

................................ ................................ ................................ . 13

5.1 Parent: Imazethapyr

................................ ................................ ................................ ........ 13

5.2 Imazethapyr Degradates

................................ ................................ ................................ . 16

5.2.1 ECOSAR

- Predicted vs. Observed Toxicity Endpoints for Parent Imazethapyr

..... 17

5.3 Review of Incident Databases

................................ ................................ ........................ 20

6 Exposure Pathways of Concern

................................ ................................ ............................ 20

7 Analysis Plan

................................ ................................ ................................ ........................ 21

7.1 Stressors of Concern

................................ ................................ ................................ ....... 21

7.1.1 Ecological Risk Assessment

................................ ................................ ................... 21

7.2 Measures of Exposure

................................ ................................ ................................ .... 22

7.2.1 Available Monitoring Data

................................ ................................ ..................... 22

7.3 Measures of Effect

................................ ................................ ................................ ......... 22

8 Endangered Species Assessments

................................ ................................ ......................... 22

9 Endocrine Disruptor Screening Program

................................ ................................ .............. 22

10 Data Gaps

................................ ................................ ................................ .............................. 22

10.1 Environmental Fate Data

................................ ................................ ............................ 23

10.2 Ecological Effects Data

................................ ................................ .............................. 24

11 R eferences

................................ ................................ ................................ ............................. 29

12 Bibliography of Cited MRIDs

................................ ................................ .............................. 29 Appendix 1. Fate Data Description

................................ ................................ ............................... 34

### 4 

## 1 Executive summary

The Environmental Fate and Effects Division (EFED) has completed the preliminary problem formulation (attached) for the ecological risk, environmental fate, endangered species, and drinking water assessments to be conducted as part of the registration review of the herbicide imazethapyr and its ammonium salt . The problem formulation describes the methods planned to be used during the completion of drinking water and ec ological r isk assessments in support of registration review and provide s an ove rview of the environmental fate, ecological effects , and potential risks associated with the use of imazethapyr and its ammonium salt as well as uncertain ties unique to risk ass essment of imazethapyr and its ammonium salt . This document also identifies additional studies that would be beneficial to the conduct of an ecological risk assessment. Major findings include:

Data needs

• There are no fate data gaps.

• While there are a nu mber of effects data gaps in the base set of data as it relates to degradates, the available lines of evidence, parent toxicity, expected environmental concentrations, structure activity data would suggest that the conduct of laboratory experiments to generate effects data in many of these situations will do very little to influence any risk conclusions. However, the following data gaps have the potential to influence the confidence of risk conclusions to a great extent:

o effects on aquatic vascular plants with the degradate CL266858 (850.4400)

o testing for parent compound direct and systemic exposures to adult and larval bees the following testing is recommended: Non

- Guideline

– Honey bee acute oral toxicity test Honey bee Larval Toxicity Test: see OECD 213 OSCPP 850.3030

– Honey bee toxicity of residues on foliage

o testing for parent with Tier 2 seedling emergence and vegetative vigor protocols 850.4100 and 850.4150 (this is a place holder pending completion of data evaluation records for submitted studies. If the submissions prove acceptable then this would no longer be required).

• These data gaps can be fulfilled using either imazethapyr or imazethapyr ammonium salt

.

Uncertainties

• Many of the labels are missing application related information

– m ax imum number of

a pp lication s per y ear , Max imum per y ear a pp lication r ate , and m inimum r etreatment i nterval

. Table 3

- 2 summarizes these issues by crop/use site.

• Owing to the vagaries of many of the labels, in the absence of information on maximum number of applications per crop cycle and per annum, and the minimum interval between applications, there are two ways the risk assessment can go forward. One is to treat labels as if they are limited to a single application per year at the labeled rate. This wou ld provide a minimum baseline risk position but may not reflect true use. The second is to

### 5 make basic assumptions for the number of crop cycles and multiple weekly applications not to exceed any stated maximum annual application. In many cases, this will prove to be a gross overestimation of environmental loading of the pesticide but would provide an upper bound to the risk assessment. It is strongly urged that, in the interests of appropriate realism, flexibility in pesticide use, and conservation of te chnical resources that discussions to resolve critical missing label information be conducted before commencement of the preliminary risk assessment.

• In the absence of data on estuarine marine organisms, the risk assessment will assume equivalent toxicity to freshwater organisms or, if data allow, the risk assessment will consider using surrogate data from the other herbicides within imazethapyr’s chemical class. This is an uncertain position, yet, given the large expected margin between estimated environ mental concentrations and freshwater toxicity endpoints, it is unlikely that the assumption will grossly underestimate nor overestimate risk to estuarine organisms relative to concern levels.



## 2 Introduction

The purpose of this problem formulation is to provide an understanding of the environmental fate and ecological effects of the registered uses of imazethapyr in support of Registration Review. Imazethapyr, an imidazolinone pesticide, is used as a selective herbicide to control grasses and broadleaved weeds including barnyardgrass, crabgrass, cocklebur, panicums, pigweeds, nightshade, mustard, smartweed, velvetleaf, jimsonweed, foxtails, seedling johnsongrass, lambsquarters, morning glory and others

. Imazet hapyr is applied primarily to soybean, alfalfa, dry beans/peas as well as genetically modified corn and rice 1 

### . Corn and rice are naturally sensitive to this herbicide; therefore, imazethapyr can only be used in imidazolinone tolerant corn and rice varieti es. It may be applied pre

- plant (soil incorporated ) , pre

- emergence, at cracking (emergence) , and post

- emergence on agricultural crops. The majority of the usage of this herbicide occurs in southern states such as Arkansas and Louisiana where is it used i n rice and in Midwestern states such as Iowa and Nebraska where it is primarily used in soybeans. There are 26 registered technical end

- use products (TEPs) containing imazethapyr ( PC code 128922) and nine TEPs containing imazethapyr, ammonium salt ( PC cod e 128923)

.
Imazethapyr is a s ystemic herbicide . It is absorbed by both roots and foliage and translocat ed via both xylem and phloem

. It accumulat es in meristematic regions ( zones of the plant where growth can take place )

.

1 A complete listing of uses includes: non - agricultural uses

– airports/landing fields, commercial/institutional/industrial premises/equipment (outdoor), industrial/construction areas (outdoor), nonagricultural rights

- of

- way/fencerows/hedgerows, nonagricult ural uncultivated areas/soils, ornamental lawns and turf, and rights

- of

- way (railroad), utility poles / rights

- of

- way and agricultural uses

– agricultural fallow/idleland/ conservation reserve, alfalfa, beans, dried

- type, beans, succulent, beans, succulent (lima), clover, corn (unspecified), corn, field, endive (escarole), garbanzos (including chick peas), lentils, lettuce, lupine, grain, ornamental sod farm (turf), peanuts, peas (unspecified), peas, dried

- type, peas, southern, peas, succulent, rice, soybea ns (unspecified), soybeans, edible, and trefoil.

### 6 The mechanism of action of imazethapyr involves reducing levels of three branc hed chain aliphatic amino acids (isoleucine, leucine and valine) through the inhibition of acetohydroxyacid synthase, an enzyme common to the biosynthetic pathway for these amino acids. This inhibition

ca uses a disruption in protein synthe sis which, in turn, leads to interference in DNA synthesis and cell growth. The mode of action is characterized by growth inhibition, chlorosis

, and necrosis over a period of weeks thereby resulting in slow death of affe cted plants

.



## 3 Previous Assessments

3.1 Ecological Risk Assessments

An ecological risk assessment for use on rice (two aerial applications per year at 0.094 lbs /A ) and clover (one aerial application per year at 0.016 lbs ai/A) was completed o n June 6, 2002 (DP 280293). This assessment made the following risk conclusions:

• Terrestrial Risks

o The potential for acute and chronic risk to birds and mammals was low.

o Imazethapyr is practically non

- toxic (LD 50 

### >1000 ug/bee) to honeybees; therefore low risk was assumed f or beneficial terrestrial invertebrates.

o Risk to terrestrial plants could not be assessed due to a lack of data. However, an evaluation of plant toxicity data for imazamox, a compound in the same class, indicate d high toxicity to non

- target terrestrial pl ants.

o There were no ecological incidents involving terrestrial organisms reported in the EFED incidents database for imazethapyr at the time of this assessment.

• Aquatic Risks

o The potential for acute and chronic risk to freshwater fish, freshwater inverteb rates and estuarine/marine invertebrates from acute exposure was found to be below concern levels.

o The potential for risk to freshwater fish from chronic exposure was found to be be low concern levels

. o Risk to estuarine/marine invertebrates and fish and fre shwater invertebrates could not be assessed because of lack of data.

o Acute risk concerns were triggered for semi

- aquatic plants exposed to rice tail

- waters. However, there was no risk concern for semi

- aquatic plants from the proposed imazethapyr use on clo ver. Additionally, there was no concern for acute risk for blue

green algae and freshwater diatom in either case.

o Two ecological incidents involving aquatic organisms (fish mortality) were reported in the EFED incidents database for imazethapyr. The linkag e between fish mortality and imazethapyr could not be established because other pesticides were detected in the aquatic environment and, given the low toxicity of the compound to these taxa, it is unlikely imazethapyr is the causal factor.

### 7 3.2 Drinking Water Assessments

A d rinking water assessment (DWA) w as performed for the use of imazethapyr on r ice and clover on June 6, 2002 (DP 280293) based on both modeling and monitoring data. Tier I Rice model results suggested that the maximum acute and chronic imazeth a pyr concentration in aquatic environments and drinking water was not expected to exceed 93 μ g/L

. This concentration is expected to be conservative because it represents imazeth a pyr concentrations in rice paddy water without consideration of degrad ation or dilution. Aquatic field dissipation studies (MRID s 45161332 and 45161333) indicate d maximum imazethapyr concentrations in rice paddy water are substantially lower (2.40 μ g/L) than model predictions. SCI

- GROW modeling predict ed peak and chronic i mazethapyr concentrations in ground water are not expected to exceed 8.97 μ g/L. P rogress reports for prospective ground water monitoring studies in Indiana and Georgia conducted at the time of this DWA indicated maximum imazethapyr concentrations in shall ow ground water ranged from 0.06 to 0.07 μ g/L.

3.3 Clean Water Act Programs

Imazethapyr is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act 2 

### . In addition, no Total Maximum Daily Load s (TMDL) have been developed for imazethapyr 3 

### . The Impaired Waters and Total Maximum Daily Loads website can be consulted for more information 4



### . Aquatic benchmarks have been established for i mazethapyr 5



### . Any data submitted or otherwise located as part of the registration review process may be used to update aquatic li fe benchmarks if applicable.

The Agency invites submission of water quality data for this pesticide. To the extent possible, data should conform to the quality standards in Appendix A of th e OPP Standard Operating Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s Registration Review Risk Assessment and Management Process 6 

### , in order to ensure they can be used quantitatively or qualitatively in pesticide risk as sessments.



## 4 Overview of Imazethapyr Use

Registered agricultural use sites for i mazethapyr and i mazethapyr ammonium salt include: agricultural fallow/idleland/ conservation reserve, alfalfa, beans, dried

- type, beans, succulent, beans, succulent (lima), clov er, corn (unspecified), corn, field, endive (escarole), garbanzos (including chick peas), lentils, lettuce, lupine, grain, ornamental sod farm (turf), peanuts, peas (unspecified), peas, dried

- type, peas, southern, peas, succulent, rice, soybeans (unspecifi ed), soybeans, edible, and trefoil. Registered non

- agricultural use sites for imazethapyr include: airports/landing fields, commercial/institutional/industrial premises/equipment (outdoor), industrial/construction areas (outdoor), nonagricultural rights

- of

- way/fencerows/hedgerows,

2 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

3 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_
gr oup_name=PESTICIDES

4 http://www.epa.gov/owow/tmdl /
5 http://www.epa.gov/oppefed1/ecorisk_ders/aquatic_life_benchmark.htm

6 http://www.epa.gov/oppfead1/cb/ppdc/2006/november06/session1

- sop.pdf

### 8 nonagricultural uncultivated areas/soils, ornamental lawns and turf, and rights

- o f

- way (railroad), utility poles/ rights

- of

- way . R egistered non

- agricultural use sites for imazethapyr ammonium salt include: airports, grasses, clover, fencerows, industrial areas, institutions, lespedeza, lupine, military installations, non

- crop ar eas, ornamental turf, rights

- of

- way, roadsides, storage yards, and tank farms.

Based on usage information provided by the Biological and Economic Analysis Division (BEAD) 7 

### , approximate total annual usage data for imazethapyr and i mazethapyr a mmonium s alt

are reported in Table 3

- 1

.

Table 3

- 1 . Screening Level Estimates of Agricultural Uses of Imazethapyr and Imazethapyr Ammonium Salt (Reporting Years: 2004

- 2011).

Crop Annual Average Lbs. A.I. Percent Crop Treated Avg. Max. Alfalfa 20,000 <2.5 <2.5 Beans, Green 1,000 10 20 Corn 30,000 <1 <2.5 Dry Beans/Peas 10,000 10 15
Peanuts 2,000 5 10 Peas, Green 3,000 40 50 Rice 100,000 30 50 Soybeans 200,000 5 10 All numbers are rounded.

< 2.5: indicates less than 2.5 percent of crop is treated. <1: indicates less tha n 1 percent of crop is treated. Screening Level Usage Analysis ( SLUA ) report data sources include: USDA

- NASS (United States Department of Agriculture's National Agricultural Statistics Service) Private Pesticide Market Research These results reflect amalgamated data developed by the Agency and are releasable to the public.



### Table 3

- 2 summarizes the application information available from EPA’s LUIS report of 12/17/13 for imazethapyr and 12/3/13 for the ammonium salt of imazethapyr. Information that could not be obtained from the LUIS report and, therefore presumably, the labels is iden tified as “NS” (not specified). If such information is not available at the time the Registration Review risk assessment is prepared, EFED will use conservative (protective of the environment) values in its modeling assumptions.

7 Per BEAD memo dated March 4, 2013 (USEPA, 2013)

### 9 Table 3

- 2 . Summary of maximum application rates, maximum number of applications, and minimum retreatment intervals by use.

Use Site Max Single App Rate (Lbs./A) Max # Apps
per C rop

C ycle M ax App Rate per C rop C ycle

(Lbs./A) Max # Apps
per Year Max App Rate per

Year (Lbs./A) Minimum Retreatment

Interval (Days) Agricultural fallow/idleland / conservation reserve 0.0668 NS NS 1 NS NA Airports/landing fields 0.1104 NS 0.2556 NS NS NS Alfalfa 0.1002 NS NS NS 0.1002 7 Beans, dried

- type 0.0501 NS NS 1 0.0501 NA Beans, succulent 0.0251 NS NS 1 0.0251 NA Beans, succulent (lima) 0.063 NS NS 1 0.063 NA Clover 0.1002 NS NS NS 0.1002 NS Commercial/institutional/industrial premises/equipment (outdoor) 0.1104 NS 0.2556 NS NS NS Corn (unspecified) 0.0628 1 0.0628 NS NS NA Corn, field 0.0668 1 NS NS 0.0668 NA Endive (escarole) 0.0331 2 NS NS NS NS Garbanzos (including chick peas) 0.0501 NS NS 1 0.0501 NA Industrial / construction areas (outdoor) 0.1104 NS 0.2556 NS NS NS Lentils 0.0501 NS NS 1 0.0501 NA
Lettuce 0.0331 2 NS NS NS NS Lupine, grain 0.0501 NS NS 1 0.0501 NA Nonagricultural rights

- of

- way/fencerows/hedgerows 0.1104 NS 0.2556 NS NS NS Nonagricultural uncultivated areas/soils 0.0758 NS NS NS NS NS Ornamental lawns and turf 0.1104 NS 0.2556 NS NS NS Ornamental sod farm (turf) 0.0758 NS NS NS NS NS
Peanuts 0.0668 NS NS NS 0.0668 NS Peas (unspecified) 0.0501 NS NS 1 0.0501 NA Peas, dried

- type 0.0501 NS NS 1 0.0501 NA Peas, southern 0.0668 NS NS 1 0.0668 NA Peas, succulent 0.0501 NS NS 1 0.0501 NA Rice 0.0993 2 0.1985 NS NS NS Rights

- of

- way (railroad) 0.0758 NS NS NS NS NS Soybeans (unspecified) 0.0681 1 0.067 NS 0.0632 NA Soybeans, edible 0.0662 1 NS 1 NS NA Trefoil 0.0662 NS NS NS 0.0662 NS Utility poles / rights

- of

- way 0.1104 NS 0.2556 NS NS NS NA = Not applicable. NS = Not specified.

### 10 

## 5 Environmental Fate Summary

It is assumed that the ammonium salt of imazethapyr dissociates rapidly and completely when mixed with water in a tank mix prior to application. The fate data are assumed to represent the imazethapyr anion, whose properties are expected to be independent of associated cations.

Imazeth a pyr is persistent and mobile in terrestrial and aquatic environments. The major dissipation pathways are photodegradation in water, surf ace water runoff, leaching and microbial

- mediated metabolism. Imazethapyr is stable to hydrolysis , but degrades via aquatic photolysis with half

- lives of ~50 hours . In a soil photolysis study, imazethapyr degraded with a half

- life greater than 4 weeks

. Imazethapyr does not appear to volatilize appreciably under environmental conditions.

In aerobic soil metabolism studies, imazethapyr degraded with half

- li ves from 158 days to
~ 1000 days

. In an anaerobic soil metabolism study, imazethapyr degraded with a half

- life of >60 days

. In an aerobic aquatic metabolism study, imazethapyr degraded with half

- li ves of 456 days ( p ond

water ) and 333 days (river water )

. In an anaerobic aquatic metabolism study, imazethapyr had half

- lives ranging from 976 days (pond water ) to >1034 days ( r iver water ).

In terrestrial field dissipation studies, i mazethapy r dissipated from the upper 3 inches of soil with half

- lives of 3 to 340 days. Aqu atic field dissipation studies yielded a ma ximum imazethapyr concentration in rice paddy water of 2.40 μ g/L . Parent dissipation was biphasic in these a qu atic field dissipat ion studies.

C hemical and fate properties of the parent and degradates are shown in Table 4

- 1 along with an identification of the studies in which the degradates are formed and the percent formation of those degradates in those studies

. An issue with eva luating imazethapyr degradates is that imazethapyr degrades so slowly that little of the degradates has formed by the end of the fate study. Therefore, the amount of any degradate present at the end of the study may not fully indicate its potential to acc umulate in the environment. Degradates of concern in the ecological risk assessment are identified in Section 5.2

.

Table 4

- 1. Structures and Basic Chemistry and Mobility Data for Imazethapyr and Imazethapyr Degradates Identified in Registrant

- Submitted F ate Studies Imazethapyr (Parent) Imazethapyr Synonym: AC 263 499 IUPAC name : 5

- ethyl

- 2

- [( RS )

- 4

- isopropyl

- 4

- methyl

- 5

- oxo

- 2

- imidazolin

- 2

- yl]nicotinic acid CAS name : 2

- [4,5

- dihydro

- 4

- methyl

- 4

- (1

- methylethyl)

- 5

- oxo

- 1H

imidazol

- 2

- yl]

- 5

- ethyl

- 3

- pyridinecarboxylic acid CAS #: 81335

- 77

- 5 Formula: C 15 H 19 N 3 O 3 Molecular Weight: 289.33 Smiles Code: n1cc(CC)cc(C(=O)O)c1C2=NC(C)(C(C)C)C(=O)N2 Measured Water Solubility: 1380 mg/L (20oC) (MRID 46854502 ) Predicted Water Solubility: 84.54 mg/L (25oC) (EPI Suite WSKOW v1.41) Measured K F : 0.622 L/kg (MRID 45161331) Predicted Koc: 339.1 L/kg (EPI Suite MCI method) N N N COOH

O

### 11 Imazethapyr Degradates in Registrant

- submitted Fate Studies CL 263501 Formula: C 16 H 21 N 3 O 3 Molecular Weight: 303.36 Smiles Code: n1cc(CC)cc(C(=O)OC)c1C2=NC(C)(C(C)C)C(=O)N2 Water Solubility: 39.12 mg/L (25oC) (EPI Suite WSKOW v1.41) Koc: 1376 L/kg (EPI Suite MCI method)

Maximum % Formation:

Soil photolysis

– 7.0% (14 days) N N N COOCH 3

O

CL 266858 CAS #: 102771

- 62 Formula: C 13 H 15 N 3 O 4 Molecular Weight: 277.28 Smiles Code: n1cc(O)cc(C(=O)O)c1C2=NC(C)(C(C)C)C(=O)N2 Water Solubility: 1964 mg/L (25oC) (EPI Suite WSKOW v1.41) Average measured non

- sand K F : 5.43 L/kg (MRID 45161331) Predicted Koc: 142.3 L/kg (EPI Suite MCI method)

Maximum % Formation :

Aerobic s oil m etabolism

– 1 1

. 74 % (increasing at study end: 124 days)

– major degradate Aquatic field dissipation

– <5% N N N COOH

O HO

CL 271 197 Synonym: 5

- Ethyl 2,3

- pyridinedicarboxylic acid CAS #: 102268

- 15

- 5 Formula: C 9 H 9 NO 4 Molecular Weight: 195.18 Smiles Code: n1cc(CC)cc(C(=O)O)c1C(=O)O Water Solubility: 7573 mg/L (25oC) (EPI Suite WSKOW v1.41) Average measured non

- sand K F : 32.1 L/kg (MRIDs 00159755, 4 5161331) Predicted Koc: 121.7 L/kg (EPI Suite MCI method)

Maximum % Formation:

Aquatic photolysis

– 8.9 % (4 days) Aquatic field dissipation

– <5% N COOH

COOH

CL 288511 CAS #: 134887

- 88

- 9 Formula: C 15 H 19 N 3 O 4 Molecular Weight: 305.34 Smiles Code: n1cc(C(O)C)cc(C(=O)O)c1C2=NC(C)(C(C)C)C(=O)N2 Water Solubility: 1405 mg/L (25oC) (EPI Suite WSKOW v1.41) Koc: 25.51 L/kg (EPI Suite MCI method)

Maximum % Formation:

Aerobic s oil m etabolism

– 1.92% (0 days; may be impurity) Aquatic field dissipation

– <5% N N N COOH

O HO

CL 288903 CAS #: 113052

- 10 Formula: C 15 H 17 N 3 O 4 Molecular Weight: 303.32 Smiles Code: n1cc(C(=O)C)cc(C(=O)O)c1C2=NC(C)(C(C)C)C(=O)N2 Water Solubility: 1012 mg/L (25oC) (EPI Suite WSKOW v1.41) Koc: 39.41 L/kg (EPI Suite MCI method)

Maximum % Formation :

Aerobic aquatic m etabolism

– 2.42 % ( 84 days) N N N COOH

O O

### 12 CL 290 084 Synonym: 5

- Ethyl 3

- pyridinecarboxylic acid Formula: C 8 H 9 NO 2 Molecular Weight: 151.17 Smiles Code: n1cc(CC)cc(C(=O)O)c1 Water Solubility: 2526 mg/L (25oC) (EPI Suite WSKOW v1.41) Average measured non

- sand K F : 0.36 L/kg (MRID 45161331) Predicted Koc: 24.92 L/kg (EPI Suite MCI method)

Maximum % Formation :

Aquatic photolysis

– 19.8 % (4 days)

– major degradate Aquatic field dissipation

– <5% N COOH

CL 290395 CAS #: 116421

- 53

- 5 Formula: C 15 H 21 N 3 O 4 Molecular Weight: 307.35 Smiles Code: n1cc(CC)cc(C(=O)O)c1C(=O)NC(C)(C(C)C)C(=O)N Water Solubility: 1494 mg/L (25oC) (EPI Suite WSKOW v1.41) Koc: 12.65 L/kg (EPI Suite MCI method)

Maximum % Formation :

Aerobic s oil m etabolism

– 1.69% (61 days) Anaerobic aquatic metabolism

– 1.0% (14 days) Aerobic aquatic m etabolism

– 0.94 % ( 14 days) N C COOH

O N H C O

NH 2

CL 354825 Formula: C 14 H 15 N 3 O 5 Molecular Weight: 305.29 Smiles Code: n1cc(C(=O)O)cc(C(=O)O)c1C2=NC(C)(C(C)C)C(=O)N2 Water Solubility: 664.2 mg/L (25oC) (EPI Suite WSKOW v1.41) Koc: 530.4 L/kg (EPI Suite MCI method)

Maximum % Formation :

Aerobic s oil m etabolism

– 3.24 % ( 42 days) A na erobic aquatic m etabolism

– 3.1 % ( 30 days) Aerobic aquatic m etabolism

– 4.76 % ( 14 days) N N N COOH

O HOOC



### Imazethapyr is expected to be mobile in soil. Total imazethapyr residues accumulated in bluegill sunfish ( Lepomis macrochirus ) with a maximum bioaccumulation factor of 1.6 × in viscera. Prospective ground water monitoring studies in Indiana and Georgia indicate maximum imazethapyr concentrations in sh allow ground water of 0.07 μ g/L. A more detailed description of the fate data for imazethapyr is available in Appendix 1

.
The fate properties of imazethapyr are presented in Table 4

- 2 for the parent only. No fate data (other than th ose presented in Table 4

- 1 ) are available for the degradates of imazethapyr.

Table 4

- 2. Fate Profile for Imazethapyr Physico

- chemical Characteristic Value Source Vapor Pressure (mm Hg @ 25oC) 5.25 × 10 - 8 MRID 46841305 Water Solubility (mg/L @ 20oC) pH 5 = 1380 ±20; pH 7 = 1380 ±10; pH 9 = 1390 ±10 MRID 46854502

Solubility in Organic Solvents ( g/L @ 20oC) n

- Heptane : 0.0226 ± 0.0003 g / L
p

- Xylene : 0.4081 ± 0.0019 g / L 1 ,2

- dichlorocthane : 33

- 40 g/L Methanol : 8 0

- 1 00 g/L Acetone: 40

- ·50 g/L Ethyl acetate: 6.71 ± 0.02 g/L MRID 46854502

Dissociation constant

– pKa 3.9 MRID 00159748 Log K OW (@2 2

- 27 oC) 1.48 ± 0.015 MRID 46854502

### 13 Physico

- chemical Characteristic Value Source
Hydrolysis Stable at pH 5 and 7 ; 257 days at pH 9 MRIDs 00159752 and 0015975 3
Photodegradation half

- life in Water 43.5 hours at pH 5 49.8 hours at pH 7 56.8 hours at pH 9 MRID 40429407

Photodegradation half

- life on Soil >28 days MRID 42918662

Aerobic Soil Metabolism half

lives ~33 months in sandy loam soil >1 year in sandy loam soil, loamy sand, and clay loam soils 158 days in sandy loam soil MRID 00159754 MRID 40074201

MRID 45161328 Anaerobic Soil Metabolism half

life >2 months in sandy loam soil MRID 40429409

A erobic Aquatic Metabolism half

lives 456 days and 333 days in a silt loam (Pond) and loam (river) sediment systems MRID 45161330

Anaerobic Aquatic Metabolism half

- lives 976 to >1034 days in silt loam (pond) and loam (River) sediment/water systems MRID 45161329

Adsorption/desorption Kf = 0.45 (1/n=0.84) in Delaware sandy loam Kf = 0.78 (1/n=0.85) in Princeton sandy loam Kf = 0.54 (1/n=0.90) in Wisconsin silt loam Kf = 0.82 (1/n=0.92) in North Dakota silt loam

Kf = 0.52 (1/n=0.89) in sandy loam soil MRID 00159755

MRID 45161329

Terrestrial Field Dissipation half

lives 4 to 14 days in 3 silt loam field plots in KY 3 to 7 days and 14 to 60 days in 2 loamy sand field plots in GA 30 to 61 days in 3 silt loam field plots in NE 61 to 117 days and 95 to 340 days in 3 loam field plots in IA 7 to 14 days and 59 to 120 days in 3 silt loam field plots in IL

36 days in loamy sand field p lots of soil in GA MRID 40429410

MRID 41467701

Aquatic Field Dissipation 8.4 days (day 0.1 to 28) and 145 days (day 28 to 359) 14 days (day 0 to 28) and > 1 year (day 14 to 360) 58 days MRID 45161333 MRID 45161332 MRID 45161341 Fish Bioaccumulation 1.6 × in viscera ; not detected in fillet and whole fish MRID 40429413



## 6 Ecological Effects Summary

6.1 Parent: Imazethapyr

Imazethapyr is an imidazolinone herbicide functioning through disruption of amino acid synthesis through inhibition of ace tolactate synthase. Shoot meristems cease growth; yellow, pink and purple symptoms appear; roots tend to develop poorly; and the secondary roots are shortened. Ballard et al. (1995) reported both xylem and phloem transport of this herbicide in two specie s of ragweed. The mechanism of action for observed toxicity in animal species is not characterized, limiting the confidence in any structure activity relationship extrapolations in situations where animal testing is absent.

Table 5

- 1 presents the available registrant

- submitted effects studies for the pesticide active ingredient and formulated products (where available)

. In the interim between this problem formulation and the commencement of the preliminary risk assessment, it is antic ipated that a search for additional information from public sources will be completed and any pertinent and scientifically sound information will be incorporated into the risk assessment process. Because both the acid and salt are expected to exist in the same a free acid state upon entering water or

### 14 the gut, it is reasonable to expect that effects data for either are interchangeable on an acid equivalent basis. The existing data set includes information on terrestrial plant toxicity and honeybee toxicity, however; as of the writing of this problem formulation, no Data Evaluation Records have been completed for these studies, so the toxicity endpoints reported herein are preliminary and subject to change upon Agency review. Moreover, while the data set inclu des both acute and chronic freshwater fish effects data, they are not paired within a common tested species, preventing the confident establishment of an acute to chronic relationship. Finally there is a lack of estuarine/marine fish and invertebrate chro nic exposure endpoints.

Animal testing with the 2ASU formulated product for invertebrates and two species of freshwater fish shows no measurable effects, and though the upper limits of the tested concentrations fall below those tested for the active ingred ient alone, no evidence is available to suggest that formulation enhances toxicity.

Table 5

- 1. Summary of the Endpoints from Toxicity Studies with Imazethapyr

Study Type TGAI/TEP (%) Species Toxicity Endpoints, Effects & Acute Toxicity Classification (I f Applicable) Source & Classification
Rat acute oral (purity not reported) Norway rat ( Rattus sp.) LD 50 > 5000 mg a.i./ /kg

- bw NOEL = 5000 mg a.i./ /kg

- bw Practically non

- toxic MRID 46854504 Acceptable

Rat acute inhalation (purity not reported) Norway rat ( Rattus sp.) LC 50 >1.487 mg a.i./ /L NOEC = 1.487 mg a.i./ /L MRID 46854506 Acceptable Rat 2

- generation reproduction (purity not reported) Norway rat ( Rattus sp.) NOEC = 10,000 mg a.i./ /kg

- diet LOEC > 10,000 mg a.i./ kg

- diet MRID 40429418 Acceptable

Avian acute oral TGAI (91.2) Bobwhite quail ( Colinus virginianus ) LD 50 > 2150 mg a.i./kg

- bw NOEL = 2150 mg a.i./kg

- bw Practically non

- toxic MRID 00159723 Acceptable

Avian acute oral TGAI (92.1) Mallard duck ( Anas platyrhynchus ) LD 50 > 2150 mg a.i./ /kg

- bw NOEL = 2150 mg a.i./ /kg

- bw Practically non

- toxic MRID 00159722 Acceptable

Avian acute oral Passerine No data

Avian sub

- acute dietary TGAI (91.2) Bobwhite quail ( Colinus virginianus ) LC 50 > 5000 mg a.i./ /kg

- diet NOEC = 5000 mg a.i./ /kg

- diet Practically non

- toxic MRID 00159725 Acceptable

Avian sub

- acute dietary TGAI (91.2) Mallard duck ( Anas platyrhynchus ) LC 50 > 5000 mg a.i./ /kg

- diet NOEC = 5000 mg a.i./ /kg

- diet Practically non

- toxic MRID 00159724 Acceptable

Avian reproduction TGAI (98.5) Bobwhite quail ( Colinus virginianus ) NOEC = 306 mg a.i./kg

- diet LOEC = 585 mg a.i./kg

- diet (eggshell thickness) MRID 45161304 Acceptable
Avian reproduction TGAI (98.5) Mallard duck ( Anas platyrhynchus ) NOEC = 1084 mg a.i./kg

- diet LOEC >1084 mg a.i./kg

- diet MRID 45161303 Acceptable Terrestrial invertebrate

acute contact Honey bee ( Apis mellifera ) Pending receipt of DER or the actual study blow

- back from Archives MRID 00159729

Terrestrial plant Tier II seedling emergence Most sensitive monocot: onion EC 25 = >0.00098 <0.0020 lb/A (weight) NOEC = > 0.00098

- 0.0020 lb/A (weight) MRID 44996102 Pending Data Evaluation. Exact endpoints selected will be established in DER Most sensitive dicot: tomato/ cabbage EC 25 = 0.0031 lb/A (weight cabbage) NOEC = 0.00098 (height tomato)

Terrestrial plant Tier II vegetative vigor Most sensitive

monocot: all tested species same NOEC = 0.031 lb/A (upper limit of study) MRID 44996101 Pending Data Evaluation.

### 15 Study Type TGAI/TEP (%) Species Toxicity Endpoints, Effects & Acute Toxicity Classification (I f Applicable) Source & Classification

Most sensitive dicot: tomato EC 25 = 0.0016 lb/A (weight) NOEC = 0.00049 lb/A (height) Exact endpoints selected will be established in DER

Freshwater fish acute TGAI (91.2) Rainbow trout ( Oncorhynchus mykiss ) 96

- hr LC 50 = 344 mg a.i./L 96

- hr NOEC < 100 mg a.i./L Practically non

- toxic MRID 00159728 Acceptable

Freshwater fish acute 2ASU formulation (22.2, corrected) Rainbow trout ( Oncorhynchus mykiss ) 96

- hr LC 50 > 24.86 mg a.i./L 96

- hr NOEC 24.86 mg a.i./L At most slightly toxic MRID45161305 Acceptable

Freshwater fish acute TGAI (91.2) Channel catfish (Ictalurus punctatus) 96

- hr LC 50 = 240 mg a.i./L 96

- hr NOEC = 180 mg a.i./L Practically non

- toxic MRID 00159726 Acceptable

Freshwater fish acute TGAI (91.2) Bluegill sunfish ( Lepomis macrochirus ) 96

- hr LC 50 = 423 mg a.i./L 96

- hr NOEC = 320 mg a.i./L Practically non

- toxic MRID 00159727 Acceptable

Freshwater fish acute 2ASU formulation (22.2, corrected) Bluegill sunfish ( Lepomis macrochirus ) 96

- hr LC 50 > 24.42 mg a.i./L 96

- hr NOEC = 24.42 mg a.i./L At most slightly toxic MRID 45161306 Acceptable

Freshwater fish chronic:Early life stage TGAI (99.3) Fathead minnow ( Pimephales promelas ) 33

- day NOEC = 97 mg a.i./L 33

- day LOEC > 97 mg a.i./L MRID 45161313 Acceptable

Estuarine/marine fish

acute TGAI (98.5) Sheepshead minnow ( Cyprinodon variegatus ) 96

- hr LC 50 > 112 mg a.i./L (im) 96

- hr NOEC = 112 mg a.i./L (im) Practically non

- toxic MRID 45161310 Acceptable

Estuarine/marine fish chronic No data

Freshwater invertebrate

acute TGAI (91.2) Water flea ( Daphnia magna ) 48

- hr EC 50 >1000 mg a.i./L NOEC = 1000 mg a.i./ L Practically non

- toxic MRID 00159729 Acceptable

Freshwater invertebrate

acute 2ASU formulation (22.2, corrected) Water flea ( Daphnia magna ) 48

- hr EC 50 > 24.42 mg a.i./L N OEC = 24.42 mg a.i./ L At most slightly toxic MRID 45161307 Acceptable

Freshwater invertebrate chronic TGAI (99.3) Water flea ( Daphnia magna ) 21

- day NOEC = 103 mg a.i./L 21

- day LOEC > 103 mg a.i./L MRID 45161314 Acceptable

Estuarine/marine invertebrate acute TGAI (99.3) Mysid shrimp ( Mysidopsis bahia ) 96

- hr LC 50 > 114 mg a.i./L 96

- hr NOEC = 114 mg a.i./L Practically non

- toxic MRID 45161311 Supplemental and suitable for quantitative use Estuarine/marine invertebrate acute TGAI (99.3) Eastern oyster ( Crassostrea virginica ) 96

- hr EC 50 > 109 mg a.i./L (mm) 96

- hr NOEC = 109 mg a.i./L Practically non

- toxic MRID 45161312 Acceptable

Estuarine/marine invertebrate chronic No data

Benthic invertebrate whole sediment No data
Aquatic non

- vascular plant 2ASU formulation (22.2, corrected) Green alga ( Selenastrum capricornutum ) 5

- day EC 50 > 22.42 mg a.i./L (mm) 5

- day NOEC = 22.42 mg a.i./L (mm) MRID 45161321 Acceptable

Aquatic non

- vascular plant 2ASU formulation (22.2, corrected) Cyanobacterium (Anabaena flos aquae) 5

- day EC 50 = 4.77 mg a.i./L (mm) 5

- day NOEC = 1.6 mg a.i./L (mm) MRID 45161320 Acceptable

### 16 Study Type TGAI/TEP (%) Species Toxicity Endpoints, Effects & Acute Toxicity Classification (I f Applicable) Source & Classification Aquatic non

- vascular plant 2ASU formulation (22.2, corrected) Freshwater diatom (Navicula pelliculosa) 5

- day EC 50 > 22.87 mg a.i./L (mm) 5

- day NOEC = 22.87 mg a.i./L (mm) MRID 45161318 Acceptable

Aquatic non

- vascular plant 2ASU formulation (22.2, corrected) Marine diatom 5

- day EC 50 > 23.09 mg a.i./L (mm) 5

- day NOEC = 23.09 mg a.i./L (mm) MRID 45161319 Acceptable

Aquatic vascular plant TGAI ( 91.6 ) Duckweed (Lemna gibba) 14

- day EC 50 = 8.1 μ g a.i./ /L NOEC = 2.8 μ g a.i./ /L MRID 41888101 Acceptable



### 6.2 Imazethapyr Degradates

There are registrant supplied effects data for three degradates, though the data are limited to aquatic invertebrate and plant toxicity ( Table 5

- 2 )

.
These data suggest that CL271197 (formed at 8.9% in aquatic photolysis studies) and CL290084 (formed at 19.8% in aquatic photolysis studies) are likely more toxic than parent imazethapyr to freshwater aquatic invertebrates, owing to the fact that some mort ality was seen in the acute tests, when none was seen at ten times the relative concentration in the parent study. These studies were classified as qualitatively supplemental because an EC 50 

### could not be calculated from the available data.

It is notable that no fish data are available for the degradates. There is considerable uncertainty on relying on invertebrate toxicity differences to make extrapolations from parent to degradates for fish toxicity. This uncertainty is founded in the finding that the a quatic invertebrate data raise concerns about enhanced toxicity relative to the parent compound and the toxicity of parent is likely greater to fish than invertebrates. However, the margins of exposure are so large ( i.e.

, exposure is expected to be orders of magnitude below effects thresholds) that conducting studies on degradates for fish would add little to the overall understanding of risks for imazethapyr and degradates.

With respect to aquatic plants, all three degradates showed some toxic activity t o the green alga Selenastrum capricornutum

. Frank effects on algae were observed with these degradates at concentrations at or below the no effect thresholds for the parent compound in the same species. However, the studies with the parent as part of the 2ASU formulation were conducted for 96 hou rs of exposure rather than the 120 hours used in degradate testing. This uncertainty regarding test duration beyond 96 hours is expected to be minor.

Table 5

- 2

. Summary of the Endpoints from Toxicity Studies with Imazethapyr Degradates

Study Type TGAI/T EP (%) Species Toxicity Endpoints, Effects & Acute Toxicity Classification (If Applicable) Source & Classification

Freshwater invertebrate acute CL266858 ( 99 ) Water flea ( Daphnia magna ) 48

- hr EC 50 > 10 0 mg a.i./L 48

- hr N OEC = 10 0 mg a.i./ L Practically non

- toxic MRID 4516130 9 Supplemental and suitable for quantitative use

Freshwater invertebrate acute CL271197 ( 99.1) Water flea ( Daphnia magna ) 48

- hr EC 50 > 100 mg a.i./L 48

- hr NOEC = 50 mg a.i./ L (mortality) Practically non

- toxic MRID 45205801 Supplemental and suitable for quantitative use

### 17 Study Type TGAI/T EP (%) Species Toxicity Endpoints, Effects & Acute Toxicity Classification (If Applicable) Source & Classification

Freshwater invertebrate acute CL290084 ( 100 ) Water flea ( Daphnia magna ) 48

- hr EC 50 > 100 mg a.i./L 48

- hr NOEC= 25 mg a.i./ L (mortality) Practically non

- toxic MRID 45161308 Supplemental and suitable for quantitative use

Aquatic non

- vascular plant CL266858 (99) Green alga ( Selenastrum capricornutum ) 5

- day EC 50 = 11.87 mg a.i./L 5

- day NOEC < 5.97 mg a.i./L MRID 45161323 Supplemental and suitable for quantitative use

Aquatic non

- vascular plant CL271197 ( 99.1) Green alga ( Selenastrum capricornutum ) 5

- day EC 50 = 12.4 mg a.i./L 5

- day NOEC < 6.87 mg a.i./L MRID 45161 327 Supplemental and suitable for quantitative use

Aquatic non

- vascular plant CL290084 ( 100 ) Green alga ( Selenastrum capricornutum ) 5

- day EC 50 = 28.77 mg a.i./L 5

- day NOEC = 6.11 mg a.i./L MRID 45161 325 Supplemental and suitable for quantitative use

Aquatic vascular plant CL271197 (99.1) Duckweed (Lemna gibba) 14

- day EC 50 > 101 u g/L 14

- day NOEC = 49.8 μ g/L MRID 4 5161326 Supplemental and suitable for quantitative use

Aquatic vascular plant CL290084 (100) Duckweed (Lemna gibba) 14

- day EC 50 = 37.15 u g/L 14

- day NOEC = 23.54 μ g/L MRID 45161324 Supplemental and suitable for quantitative use



### 6.2.1 ECOSAR

- Predicted vs. Observed Toxicity Endpoints for Parent Imazethapyr

ECOSAR predictions based on amide structure activity relationships are shown in Table 5

- 3 for all degradates for fish, daphnids and green algae, the taxa for which the quantitative structure activity model can predict effect endpoint s

. In general, the QSAR is poorly predictive of actual observed toxicity in parent imazethapyr. Only a few gen eral statements can be made about the accuracy of QSAR predictions and only for daphnid and green algal toxicity because there are limited test data for the degradates. For CL288858, there appears to be good agreement between QSAR and observed effects. T his compound is quite structurally similar to the parent so the reason for chemical

- specific disparities in the relative agreement between QSAR and empirical cannot be explained by drastic structural differences between the compounds. In the other cases

o f available experimentally derived toxicity (CL290084 and CL271197 ), there is poor agreement between QSAR and empirical findings. It is notable, however, that CL290084 and CL271197 are not amides, but rather carboxylated pyridines and so the amide QSAR is likely a poor fit. The only other QSAR applied by ECOSAR was the neutral organic relationship, which even further under

- predicts toxicity relative to observations. From these findings, it appears the available QSAR predictions for degradates are inappro priate for quantitative risk assessment use.

Nevertheless, the relative differences in toxicity are moot compared to the likely levels of exposure expected to be encountered in the environment. Past imazethapyr ecological risk assessments predi cted aquatic concentrations in the μg/L range. All of the degradate toxicity predictions and empirical measures of toxicity for animals and unicellular aquatic plants are several orders of magnitude higher than predicted concentrations of the parent. Giv en the relatively long persistence of the parent compound expected in the envir onment, the low percentage of applied material identified as degradates, and the low toxic potency based on QSAR and available empirical data, it appears that their inclusion fo r quantitative consideration

### 18 in the risk assessment for aquatic animals and unicellular aquatic plants will not significantly alter assumptions of stressor exposure beyond the parent herbicide itself. However, CL271197 and CL290084 both exhibit substantia l aquatic vascular plant toxicity on par with the parent compound. These and CL266858, which is structurally very similar to the parent herbicide, all constitute substantial fractions of activity in the fate studies and should be retained as stressors of concern for aquatic exposure and risk assessment for vascular plant taxa.

### 19 Table 5

- 3. ECOSAR

- predicted and Observed Toxicity Values for Imazethapyr and Major Degradates

Taxon Exposure duration (Units in mg/L) Imazethapyr CL271197 CL290084 CL263501 CL288511 CL290395 CL266858 CL354825 CL288903 8.9% 19.8% 7% 1.9% 1.7% 11.7% 4.8% 2.4% Obs. QSAR Obs. QSAR Obs. QSAR Obs. QSAR Obs. QSAR Obs. QSAR Obs. QSAR Obs. QSAR Obs. QSAR Freshwater fish 96

- hr LC 50 240 12 40 ND 220 ND 2026 9 ND 7. 6 ND 215 5 ND 2354 9 ND 188 8 ND 1075 8 ND 15407 Chronic value 97 7.3 ND 18.5 ND 2083 ND 0.045 ND 12.7 ND 139 ND 11.2 ND 63.6 ND 91.1 Daphnid 48

- hr EC/LC 50 >1000 860 >100 (mort. >50) 62 4 >100 (mort. >25) 1102 7 ND 5.8 ND 1346 ND 9457 >100 775 ND 5006 ND 6689

Chronic Value 103 11. 4 ND 47.6 ND 122 4 ND 0.077 ND 11. 6 ND 12 5 ND 10.2 ND 66.0 ND 88.2 Green algae 96

- hr EC 50 >22.4 48.3 12.4 17 3 28.77 464 4 ND 0.37 ND 12.2 ND 12 7 11.9 11.0 ND 95.6 ND 108.1 ND = not determined; Obs. = observed

### 20 6.3 Review of Incident Databases

Reviews on September 25, 2013 of the Ecological Incident Information System 8 

### (EIIS, version 2.1.1), which is maintained by the Agency’s Office of Pesticide Programs, and the Avian Monitoring Information System (AIMS), which is maintained by the American Bird Conservatory, indicate no reported ecological incidents (in EIIS) associa ted with the use of imazethapyr.

In addition to the incidents recorded in EIIS and AIMS, additional incidents are reported to the Agency in aggregated form. Pesticide registrants report certain types of incidents to the Agency as aggregate counts of inci dents occurring per product per quarter. Ecological incidents reported in aggregate reports include those categorized as ‘minor fish and wildlife’ (W

- B), ‘minor plant’ (P

- B), and ‘other non

- target’ (ONT) incidents. ‘Other non

- target’ incidents include re ports of adverse effects to insects and other terrestrial invertebrates. For imazethapyr, registrants have reported no minor fish and wildlife incidents, 399 minor plant incidents, and no other non

- target incidents as of September 25, 2013.

The total number of actual incidents associated with the use of imazethapyr may be higher than what is reported to the Agency. Incidents may go unreported since effects may not be immediately apparent and/or readily attributed to the use of a chemical.



## 7 Exposure Pat hways of Concern

For terrestrial vertebrates, the major route of exposure to imazethapyr is considered to be via dietary ingestion of food items such as plants and/or animals that have imazethapyr residues as a result of direct application, spray drift, a nd runoff. Exposure of terrestrial vertebrates through inhalation is considered unlikely to be a pathway of concern for birds or mammals as there are no demonstrated toxic effects to birds and mammals. Given the lack of demonstrated acute oral toxicity t o birds and mammals and the low expected application rates of the compound

, assessment of drinking water exposure to wildlife is not warranted. Moreover

, using the water solubility of imazethapyr as a surrogate for oral dose ( i.e. , assuming 100 percent bo dyweight consumption as drinking water) yields a theoretical maximum dose of the compound well below levels demonstrated to produce no acute effects

.
For terrestrial invertebrates, the major routes of exposure to imazethapyr are considered to be direct co ntact as a result of direct application and spray drift and dietary ingestion of plants, animals, and/or soil that have imazethapyr residues as a result of direct application, spray drift, and runoff. Exposure to terrestrial invertebrates could also occur through guttation water.

For aquatic animal species, the major route of exposure to imazethapyr is considered to be uptake via the respiratory surface (gills) or the integument from surface water/sediment that has imazethapyr residues as a result of spra y drift, and runoff

.

8 http://www.epa.gov/espp/consultation/ecorisk

- overview.pdf

### 21 For terrestrial (upland and semi

- aquatic) non

- target plants, the major routes of exposure to imazethapyr are considered to be direct contact as a result of direct application and spray drift and root uptake via soil contaminated via s pray drift and runoff.

For aquatic plants, the major routes of exposure to imazethapyr are considered to be uptake from surface water/sediment containing imazethapyr residues as a result of spray drift, and runoff

.



## 8 Analysis Plan

During the risk assessmen t process , the potential for adverse effects on the environment will be estimated. Usage, environmental fate, and ecological effects of imazethapyr will be characterized and integrated to assess the risks. Risk quotients (RQs) will be derived for imazeth apyr by dividing estimated exposure concentrations ( EEC s) by the most sensitive endpoint from the relevant, available toxicity data for imazethapyr and the degradates where existing toxicity indicate the potential for biologically significant effects ( e.g. , aquatic vascular plant risk assessment ). As outlined in the Overview Document (USEPA, 2004), the likelihood of effects to individual organisms from particular uses of a chemical is estimated using the probit dose

- response slope and either the level of c oncern (LOC) or the actual calculated risk quotient value.

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

8.1 Stressors of Concern

8.1.1 Ecological Risk Assessment

The risk assessment will consider pa rent imazethapyr and three degradates that constitute substantial fractions of activity in the fate studies. Imazethapyr and CL266858 are structurally very similar and will be analyzed in common. CL271197 and CL290084 will be analyzed separately as there is no evidence of a common mechanism of action.

8.1.1 Drinking Water Assessment

No drinking water assessment will be conducted fo r imazethapyr as part of the Registration Review process. The most recent dietary

- exposure assessment was performed for the November 2005 human health risk assessment and no risks of concern were identified

. Since it has been determined that a qualitative assessment is sufficient based on the low toxicity of imazethapyr, a quantitative dietary exposure assessment is not needed for Registration Review for HED to conclude with reasonable certainty that dietary exposures to imazethapyr do not pose a significa nt human health risk.

### 22 8.2 Measures of Exposure

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

.
8.2.1 Available Monitoring Data

The Agency is aware of monitoring conducted by federal and state agencies and this data will be considered in the assessment to the extent that data on imazethapyr are available.

8.3 Measures of Effect

Toxi city data presented in Section 5 of this problem formulation will be used to calculate risk quotients. Any additional information submitted by the registrant or found in the open literature prior to conduct of the risk assessment will also be considered. The open literature studies are identified using EPA’s ECOTOXicology database ( ECOTOX) , which employs a literature search engine for locating chemical toxicity data for aquatic life, terrestrial plants, and wildlife. The evaluation of both s ources of data can also provide insight into the direct and indirect effects of pesticides on biotic communities from loss of species that are sensitive to the chemicals and from changes in structure and functional characteristics of the affected communiti es.



## 9 Endangered Species Assessments

Consistent with the Agency’s responsibility under the Endangered Species Act (ESA), the Agency will evaluate risks to Federally

- listed threatened and/or endangered (listed) species from registered uses of imazethapyr . T his assessment will be conducted i n accordance with the Overview Document (USEPA, 2004), provisions of the ESA, and the Services’ Endangered Species Consultation Handbook (USFWS/NMFS, 1998). The process for evaluating potential risks to listed species is further described at http://www.epa.gov/oppfead1/endanger/litstatus/riskasses.htm

. An endangered species assessment has not been conducted for imazethapyr to date.



## 10 Endocrine Disruptor Screening Program

Imazethapyr was not included in the first group of 67 chemicals , n or the second group of 109 chemicals, issued an order to conduct Tier 1 EDSP testing. For additional information the EDSP program, visit http://www.epa.gov/endo/

.



## 11 Data Gaps

The following two sections identify environmental fate and effect s data that are needed to complete an environmental fate and ecological risk assessme nt in support of the Registratio n R eview of the registered uses of imazethapyr.

### 23 11.1 Environmental Fate Data

Table 11

- 1 lists the status of the fate and transport data requirements for imazethapyr. The fate database for imazethapyr is complete. No additional fate data are required at this time ( Table 10

- 1 ).

Table 11

- 1. Registrant

- Submitted Fate Data for Imazethapyr and Remaining Data Gaps

Guideline Description MRID/ Source Classification Data Gap?

835.2120 161

- 1 Hydrolysis 00159752 00159753 Supplemental Acceptable No , but see text immediately below this table.

835.2240 161

- 2 Photodegradation in Water 40429407 Supplemental No

835.2410 161

- 3 Photodegradation in Soil 40429408 Supplemental No

835.4100 162

- 1 Aerobic Soil Metabolism 40074201 40522601 45161328 Acceptable Acceptable Supplemental No

835.4200 162

- 2 Anaerobic Soil Metabolism 40429409 Acceptable No

835.4300 162

- 4 Aerobic Aquatic Metabolism 45161330 Supplemental No

835.4400 162

- 3 Anaerobic Aquatic Metabolism 45161329 Acceptable No

835.1230 835.1240 163

- 1 Leaching

- Adsorption/ Desorption 00159755 45161331 Acceptable Acceptable No

835.6100 164

- 1 Terrestrial Field Dissipation 40429410 40490101 41467701 Supplemental Acceptable No

835.6200 164

- 2 Aquatic Field Dissipation 45161332 45161333 45161341 Supplemental No

850.6100 Analytical Method

- Soil 44865103 Supplemental No

850.6100 Analytical Method

- Water 45161338 44746701 Supplemental No

850.6100 Analytical Method

- Sediment 45161337 Supplemental No

850.1730 165

- 4 Accumulation in fish 40429413 Supplemental No

840.2100 166

- 2 Ground Water

- small retrospective 461237 02 In review No

### 24 11.2 Ecological Effects Data

Table 11

- 2 provides ecologic al effects studies by MRID that offer data for each guideline requirement as well as study classifications and whether or not f urther data are needed to support the Registration Review ecological risk assessment ( i.e.

, whether there is a data gap).

Table 11

- 2. Registrant

- Submitted Ecological Effects Data for Imazethapyr/Degra dates and Remaining Data Gaps

Guideline Description MRID/Source * Classification Data Needed for Risk Assessment Justification

850.1010 Acute toxicity freshwater invertebrates 00 159729 45161307 45161309 (CL266858) 45205801 ( CL271197 ) 45161308 ( CL290084 ) Acceptable Acceptable Supplemental Supplemental Supplemental No

850.1025 850.1055 Acute toxicity estuarine/marine mollusk 45161312 Acceptable No

850.1035 850.1045 Acute toxicity estuarine/marine invertebrate 45161311 Supplemental No T he study provides sufficient information for quantitative use

.

850.1075 Acute toxicity freshwater fish (cold water species) 00 159728 45161312 Acceptable

No Acute toxicity freshwater fish (warm water species) 00 159727 4516130 5 45161306 00 159726 Acceptable

Acute toxicity estuarine/marine fish 45161310 Acceptable No

850.1300 Aquatic invertebrate life cycle (freshwater) 45161314 Acceptable No

850.1350 Aquatic invertebrate life cycle (saltwater) -- -- No T he utility of conducting a study is extremely limited because available chronic data and past exposure estimates are many orders of magnitude apart

.

850.1400 Fish early life

stage (freshwater) 45161313 Acceptable No

### 25 Guideline Description MRID/Source * Classification Data Needed for Risk Assessment Justification

Fish early life

stage (saltwater) -- -- No The utility of conducting a study is extremely limited because available chronic data and past exposure estimates are many orders of magnitude apart.

850.2100 Avian oral toxicity (upland game or waterfowl species) 00 159723 00 159722 Acceptable Acceptable No

Avian oral toxicity (passerine species) -- -- No A vian acute oral toxicity data for a passerine species are required under the new 40 CFR Part 158. However, the expected exposure levels are likely to be orders of magnitude below limit tolerated exposures for two tested species. If no other effects other

t han direct lethality are of concern then the available lines of evidence would suffice for the risk

assessment. Regurgitation effects in passerines are a possibility for this chemical based on such effects encountered with other relatively non

toxic acidi c compounds tested with passerines

.

850.2200 Avian dietary toxicity (upland game species) 00 159725 Acceptable No

Avian dietary toxicity (waterfowl species) 00 159724 Acceptable No

### 26 Guideline Description MRID/Source * Classification Data Needed for Risk Assessment Justification

850.2300 Avian reproduction (upland game species) 45161304 Acceptable No

Avian reproduction (waterfowl species) 45161303 Acceptable No

850.3020 Honey bee acute contact toxicity 00 159729 Pending Review Yes

850.3030 Honey bee toxicity of residues on foliage -- -- Yes ; The need for the study depends on the final review of 850.3 0 20

Non

guideline Honey bee acute oral toxicity -- -- Yes The need for the study depends on the final review of 850.3 0 20

Non

guideline Honey bee l arval

t oxicity -- -- Yes The need for the study depends on the final review of 850.3 0 20

850.4100 Seedling
emergence (terrestrial plants) 44996102 Pending Review Yes

- pending DER Studies establishing the non

- target plant toxicity for herbicides is essential for establishing the extent of off

- site drift impacts

850.4150 Vegetative vigor (terrestrial plants) 44996101 Pending Review Yes

- pending DER Studies establishing the non

- target plant toxicity for herbicides is essential for establishing the extent of off

- site drift impacts

850.4400 Aquatic plant growth (aquatic vascular plant toxicity) 41888101 45161326 ( CL271197 ) 45161324 ( CL290084 ) ( CL266858 ) Acceptable Supplemental Supplemental No valid study Yes ( CL266858 ) QSAR and structural similarity suggest degradate CL266858 is likely substantially toxic to vascular aquatic plants . Owing to the predictions of high toxicity, the endpoint for this degradate suggests High Potential to Affect Risk Assessment

.

### 27 Guideline Description MRID/Source * Classification Data Needed for Risk Assessment Justification

850.4500 Aquatic plant growth (aquatic non

vascular plant: algal toxicity) 45161318 Acceptable No

45161321 45161323 ( CL266858 ) 45161327 ( CL271197 ) 45161325 ( CL290084 ) Acceptable Supplemental Supplemental Supplemental No

45161319 Acceptable No

850.4550 Aquatic plant growth (aquatic non

vascular plant: cyanobacteria toxicity) 45161320 Acceptable No

* conducted with parent imazethapyr unless otherwise noted



### Strategies to address data gaps within the imazethapyr parent data include:

Terrestrial Plant Toxicity : As an herbicide, these endpoints are critical to an understanding of the extent to which herbicide activity will impact non

- target plants off the site of application. It is recommended that Tier 2 plant seedling emergence and vegetative vigor testing be conducted with an appropriate formulated end use product at labeled maximum application

rate.

Avian Acute Oral Toxicity (Passerine): The available data show no adverse effects in both quail and mallard ducks for acute effects at oral doses in excess of 2000 mg/kg

- bw and dietary concentrations as high as 5000 mg/kg

- diet. Using an expected maximum application rate of 0.125 lb a.i./A yie lds an upper bound estimate of dietary concentrations of 230 mg/kg

- diet (short grass). This is two orders of magnitude below concentrations in the tested species showing no ill effects. The likelihood that passerines will exhibit acute lethal effects in a classical biochemical cascade at a level so much lower than the tested species to trigger acute concerns is low. However, passerine testing with other low toxicity compounds has suggested that passerines may be intolerant of some pesticides in a manner that stimulates regurgitation and reduced feeding. Regurgitation and reduced feeding may result in lethal effects or reduced reproduction in migratory bird species. This is an uncertain area regarding the manifestation of regurgitation with this compound, and the evaluation of the level of regurgitation and circumstances where such an effect could lead to impaired organism fitness. Should these endpoints be of concern to risk managers when making regulatory decisions on imazethapyr, acute testing of a pass erine species would provide information on this type of response.

Terrestrial Invertebrate Toxicity (Honey bee): The nature and timing of imazethapyr applications (early and late growth stage timing) suggest a variety of opportunities for the herbicide to be applied when plants may be in bloom and attractive to pollinators. The empirically demonstrated xylem and phloem transport of the chemical in two species of ragweed suggest that there is a potential for residues to be transported to pollinator attract ive portions of plants. Therefore, to evaluate the potential for direct and systemic exposures to adult and larval bees the following testing is recommended:

### 28 OECD 213

– Honey bee acute oral toxicity test Honey bee Larval Toxicity Test: Non

- Guideline OS CPP 850.3030

– Honey bee toxicity of residues on foliage

Estuarine/Marine Species Chronic Toxicity: The available estimated environmental concentrations in surface water derived from past imazethapyr risk assessments place parent concentrations several o rders of magnitude below acute and chronic adverse effects thresholds in freshwater species and acute no effect thresholds in estuarine/marine species. It is highly unlikely that estuarine/marine invertebrates will exhibit chronic sensitivities orders of magnitude higher than freshwater species. Therefore, there appears to be no practical reason to conduct chronic testing with estuarine/marine fish and invertebrates at this time, and the results for freshwater animals will be considered appropriately cons ervative to characterize the risk to estuarine/marine fish and invertebrates.

Benthic Whole Sediment Testing: No data are available for benthic organisms ; however

, given the low affinity for o rganic carbon and low acute and chronic toxicity of the pestic ide to aquatic invertebrates, imazethapyr does not meet criteria for inclusion of this study type as a data gap.

Strategies to address data gaps within the imazethapyr degradate data include:

Aquatic Plant Toxicity : CL266858 has been tested with aquatic macrophyte ( Lemna sp.) , but the study was classified as invalid. Therefore, a repeat of this study is recommended to provide an effects endpoint for aquatic vascular plants for this degradate. In the absence of acceptable data, the compound may be considered of equal toxicity as the parent herbicide, or an extrapolation from available structural analogs’ toxicity relative to parent will be used to establish an endpoint.

For the other species constituting a Ti er 2 aquatic plant toxicity d ata set, there appears to be no benefit afforded to the certainty of a risk assessment that would assume equipotence with
p a rent in the absence of any emp irical testing.

### 29 

## 12 References

Ballard, T.O., M

. E. Foley and T

. T. Bauman

. 1995

. Absorption, Translocation, and Metabolism of Imazethapyr in Common Ragweed ( Ambrosia artemisiifolia ) and Giant Ragweed ( Ambrosia trifida ) . Weed Scien ce. Vol. 43, No. 4 (Oct.

- Dec., 1995), pp. 572

- 577.

USEPA. 2013. Case Level Imazethapyr (128922) and Imazethapyr Ammonium Salt (128923) Screening Level Usage Analysis (SLUA). March 4, 2013 . 2pp.



## 13 Bibliography of Cited MRIDs

Fate Studies

00159752 Gingher, B. (1984) AC 263,499: The Hydrolysis of Carbon

- 14 Labeled AC 263,499 in Pond Water: Project Number 0533: Report No.: PD

- M Volume 21

- 12. Unpublished study prepared by American Cyanamid Company. 13 p.

00159753 Gingher, B.; Barringer, D. (1985) Herbicide AC 263,499: The Hydro

- lysis of Carbon

- 14 Labeled AC 263,499 in Buffered Aqueous Solu

- tions: Project Number 0533: Report No.: PD

- M Volume 22

- 41. Un

- published study prepared by American Cyanamid Company. 32 p.

40429407 Mallipudi, M. (1987) Purs uit Herbicide (AC 263,499): Photolysis of Pyridine Ring

- 6 Carbon

- 14 Labeled AC 263,499 in Aqueous Media: Laboratory Report No.: PD

- M Volume 24

- 29. Unpublished study prepared by American Cyanamid Co. 64 p.

40429408 Mangels, G. (1987) Pursuit Herbicide (AC 263,499): Soil Photolysis: Laboratory Report No.: PD

- M Volume 24

- 20. Unpublished study prepared by American Cyanamid Co. 25 p.

00159754 Mallipudi, M. (1985) AC 263,499 Herbicide: A Laboratory Aerobic Metabolism Study of Pyridine Ring

- 6 Carbon

- 14 Labeled A C 263,499 (2

- [4,5

- Dihydro

- 4

- methyl

- 4

- (1

- methyl

- ethyl)

- 5

- oxo

- 1H

imidazol

- 2

- yl]

- 5

- ethyl

- 3

- Pyridinecarboxylic Acid] in Sandy Loam Soil: Proj

- ect Number 0533: Report No.: PD

- M Volume 22

- 43. Unpublished study prepared by American Cyanamid Company. 44
p.

4007 4201 Mallipudi, M. (1987) Pursuit Herbicide (AC 263,499): A Laboratory Aerobic Soil Metabolism Study of Pyridine Ring

- 6 Carbon

- 14 Labeled AC 263,499 (2

- [4,5

- dihydro

- 4

- methyl

- 4

- (1

- methylethyl)

- 5

-
oxo

- 1H

- imidazol

- 2

- yl]

- 5

- ethyl

- 3

- pyridinecarboxylic acid) in S andy Loam Soil: Laboratory Report No. PD

- M Volume 24

- 5. Unpub

- lished study prepared by American Cyanamid Co. 47 p.

40522601 Mangels, G.; Guzman, B. (1988) AC 263,499 Herbicide: Confirmation of Levels of AC 263,499 in Soils from Aerobic Soil Metabolism St udies: Report No. C

- 3057.2. Unpublished study prepared by American Cyanamid Co. 27 p.

45161328 Ta, C. (1998) AC 263499: Aerobic Soil Metabolism: Lab Project Number: ENV 97

- 009: ENV 97

- 009.01: E

- 97

- 009. Unpublished study prepared by American Cyanamid Co. 1 22 p.

40429409 Mallipudi, M. (1987) Pursuit Herbicide (AC 263,499): A Laboratory Anaerobic Soil Metabolism Study of Pyridine Ring

- 6 Carbon

- 14 Labeled AC 263,499 (2

- [4,5

- dihydro

- 4

- methyl

- 4

- (1

- methylethyl)

- 5

- oxo

- 1H

- imidazol

- 2yl]

- 5

- ethyl

- 3

- pyridinecarboxylic acid) in Sandy Loam Soil: Laboratory Report No.: PD

- M Volume 24

- 25. Unpublish

- ed study prepared by American Cyanamid Co. 34 p.

### 30 45161329 Reynolds, J.; Rice, P. (2000) Imazethapyr (AC 263499): Anaerobic Aqu atic Metabolism Study: Lab Project Number: ENV 98

- 017: XBL98023. Unpublished study prepared by American Cyanamid Co. and XenoBiotic Labs., Inc. 170 p.

45161330 Reynolds, J.; Rice, P. (2000) Imazethapyr (AC 263499): Aerobic Aquatic Metabolism Study: Lab Pr oject Number: ENV 98

- 016: XBL98024. Unpublished study prepared by American Cyanamid Co. and XenoBiotic Labs., Inc. 172 p.

00159755 Gingher, B. (1985) AC 263,499: Soil Adsorption and Desorption Study of AC 263,499, (+)

- 2

- [4,5

- Dihydro

- 4

- methyl

- 4

- (1

- methylet hyl)

- 5

- oxo

- 1H

- imidazol

- 2

- yl]

- 5

- ethyl

- 3

- Pyridinecarboxylic Acid: Project Number 0533: Report No.: PD

- M Volume 22

- 27. Unpublished study prepared by American Cyanamid Company. 70 p.

45161331 Ta, C. (1999) Imazethapyr (AC 263499)and its Transformation Produc ts CL 266858, CL 271197, CL 290084: Adsorption/Desorption on Soils: Lab Project Number: ENV 98

- 040: E 98

- 040. Unpublished study prepared by American Cyanamid Co. 300 p.

40429410 Guzman, B.; Tondreau, F.; Arnold, T. (1987) Pursuit Herbicide (CL 263,499): R esidues of CL 263,499 in Soil: Laboratory Report Nos.: C

- 2817: C

- 2971: C

- 2972. Unpublished study prepared by American Cyanamid Co. 546 p.

40490101 Guzman, B.; Tondreau, F.; Arnold, T. (1988) Additional Data for Volume 13: Pursuit Herbicide (CL 263,499): Residues of CL 263,499 in Soil: Report Nos. C

- 2817, C

- 2951 and C

- 2971. Unpublished study performed by American Cyanamid Company. 3 p.

41467701 Guzman, B.; Taylor, F. (1989) Imazethapyr (CL 263,499/2AS): Resi

- dues of CL 263,499 in Soil (PPI;Loamy Sand, GA , 1988): Lab Project Number: C

- 3185. Unpublished study prepared by American Cyanamid Co. 87 p.

45161332 Cavalier, T.; Shen, X.; Xu, B. et al. (2000) CL 263499 (Imazethapyr): Residues of CL 263499, CL 266858, CL 290084 and CL 271197 in Water, Soil, and Sed iment After a Sequential Preemergence and Postemergence Treatment with Pursuit 70DG Herbicide in Arkansas: Lab Project Number: CY 318: RES 99

- 032: RES 99

- 011. Unpublished study prepared by American Cyanamid Co. and Centre Analytical Labs., Inc. 521 p.

451 61333 Xu, B.; Shen, X.; Stout, S. et al. (2000) CL 263499 (Imazethapyr): Residues of CL 263499, CL 266858, CL 290084 and CL 271197 in Water, Soil, and Sediment After a Sequential Pre

- Plant Incorporated and Postemergence Treatment with Pursuit 2AS Herbicide in Louisiana: Lab Project Number: RES 99

- 047: RES 99

- 068: RES 99

- 082. Unpublished study prepared by American Cyanamid Co. and Centre Analytical Labs., Inc. 629 p.

45161341 Ta, C.; Xia, C. (1998) AC 263499 ((carbon 14)

- Imazethapyr): Degradation and Metabo lism in Soils Cultivated with Rice Under Outdoor, Simulated Paddy Conditions: Lab Project Number: ENV 97

- 015: 43993. Unpublished study prepared by American Cyanamid Co. and ABC Labs., Inc. 90 p.

40429413 Forbis, A. (1987) Uptake, Depuration and Bioconcent ration of [Car

- bon 14]

- AC 263,499 by Bluegill Sunfish (Lepomis macrochirus): Laboratory Report No. 34643. Unpublished study prepared by Ana

lytical Bio

- Chemistry Laboratories, Inc. 229 p.



### Ecological Effects Studies

159722 Fletcher, D. (1985) Acute Oral Toxicity Study with AC 263,499 in Mallard Ducks: Final Report: BLAL No. 85 DD 28. Unpublished study prepared by Bio

- Life Associates, Ltd. 26 p.

159723 Fletcher, D. (1985) Acute Oral Toxicity Study with AC 263,499 in Bobwhit e Quail: Final Report: BLAL No. 85 QD 54. Unpublished study prepared by Bio

- Life Associates, Ltd. 26 p.

159724 Fletcher, D. (1985) 8

- Day Dietary LC50 Study with AC 263,499 in Mallard Ducklings: Final Report:

### 31 BLAL No. 85 DC 54. Unpublished study prepared by Bio

- Life Associates, Ltd. 28 p.

159725 Fletcher, D. (1985) 8

- Day Dietary LC50 Study with AC 263,499 in Bobwhite Quail: Final Report: BLAL No. 85 QC 53. Unpublished study prepared by Bio

- Life Associates, Ltd. 28 p.

45161303 Ahmed, S.; Baroch, J.; Fuh rman, V. et al. (2000) Avian Reproduction Test with Imazethapyr (AC 263499 Technical) in Mallard Duck (Anas platyrhynchos): Lab Project Number: ECO 98

- 117. 01: 954

- 98

- 401: 98009. Unpublished study prepared by American Cyanamid Co. and Genesis Labs., Inc. 2 05 p. {OPPTS 850.2300}

45161304 Ahmed, S.; March, K.; Fuhrman, V. et al. (2000) Avian Reproduction Test with Imazethapyr (AC 263499 Technical) in Northern Bobwhite (Colinus virgianus): Lab Project Number: ECO 98

- 116: 954

- 98

- 401: CY 317. Unpublished study prepared by American Cyanamid Co. and Genesis Labs., Inc. 217 p. {OPPTS 850.2300}

159726 McAllister, W.; Bowman, J.; Cohle, P. (1985) Acute Toxicity of AC 263,499 to Channel Catfish (Ictalurus punctatus): Static Acute Toxicity Report #33058. Unpublished study prepared by Analytical Bio

- Chemistry Laboratories, Inc. 55 p.

159727 McAllister, W.; Cohle, P.; Bowman, J. (1985) Acute Toxicity of AC 263,499 to Bluegill Sunfish (Lepomis macrochirus): Static Acute Toxicity Report #33056. Unpublished study prepared by Analytical Bio

- Chemistry Laboratories, Inc. 55 p.

159728 McAllister, W .; Bowman, J.; Cohle, P. (1985) Acute Toxicity of AC 263,499 to Rainbow Trout (Salmo gairdneri): Static Acute Toxi

- city Report #33057. Unpublished study prepared by Analytical Bio

- Chemistry Laboratories, Inc. 52 p.

40933001 Boyd, J. (1988) Response to EEB Review of the Registration Applica

- tion Concerning the Freshwater Fish Studies: Pursuit Herbicide. Unpublished study prepared by American Cyanamid Co. 4 p.

45161305 Krueger, H.; Nixon, W.; Palmer, S. et al. (2000) Acute T oxicity of a 2ASU Formulation of AC 263499 (Imazethapyr) to Rainbow Trout, Oncorhynchus mykiss, Under Flow

- Thorugh Test Conditions: Lab Project Number: ECO 98

- 154: ECO 98

- 411: CY 299. Unpublished study prepared by American Cyanamid Co. and Wildlife Interna tional Ltd. 133 p. {OPPTS 850.1075}

45161306 Krueger, H.; Nixon, W.; Palmer, S. et al. (2000) Acute Toxicity of a 2ASU Formulation of AC 263499 (Imazethapyr) to Bluegill, Lepomis macrochirus, Under Flow

- Through Test Conditions: Lab Project Number: ECO 98

- 153: ECO 98

- 411: CY 308. Unpublished study prepared by American Cyanamid Co. and Wildlife International Ltd. 133 p. {OPPTS 850.1075}

45161307 Krueger, H.; Nixon, W.; Palmer, S. et al. (2000) Acute Toxicity of a 2ASU Formulation of AC 263499 (Imazethapyr ) to Daphnia magna Under Flow

- Thorugh Test Conditions: Lab Project Number: ECO 98

- 155: ECO 98

- 411: CY 305. Unpublished study prepared by American Cyanamid Co. and Wildlife International Ltd. 133 p. {OPPTS 850.1010}

45161308 MacGregor, J.; Nixon, W.; Mull igan, E. et al. (2000) Acute Toxicity of CL 290084 to Daphnia magna Under Static Test Conditions: Lab Project Number: ETX 99

- 129: ECO 98

- 411: CY 321. Unpublished study prepared by American Cyanamid Co. and Wildlife International Ltd. 128 p. {OPPTS 850.1010 }

45161309 MacGregor, J.; Nixon, W.; Mulligan, E. et al. (2000) Acute Toxicity of CL 266858 to Daphnia magna Under Static Test Conditions: Lab Project Number: ETX 99

- 126: ECO 98

- 411: CY 320. Unpublished study prepared by American Cyanamid Co. and Wildlife International Ltd. 124 p. {OPPTS 850.1010}

45205801 Mac Gregor, J.; Mulligan, E.; Nixon, W.; et al. (2000) Acute Toxicity of CL 271197 to Daphnia magna under Static Test Conditions: Lab Project Number: ETX 99

- 132: ECO 98

- 411: 130C

- 107. Unpublished study prepared by American Cyanamid Company and Wildlife Interna tional Ltd. 127 p. {OPPTS 850.1010}

159729 Forbis, A.; Georgie, L.; Burgess, D. (1985) Acute Toxicity of AC 263,499 to Daphnia magna: Static

### 32 Acute Toxicity Report #33059. Unpublished study prepared by Analytical Bio

- Chemistry Labora

tories, Inc. 37 p.

45161310 MacGregor, J.; Nixon, W.; Palmer, S. et al. (2000) Acute Toxicity of AC 263499 Technical (Imazethapyr) to Sheepshead Minnow (Cyprinodon variegatus) Under Static

- Renewal Test Conditions: Lab Project Number: ECO 98

- 148: ECO 98

- 411: CY 309. Unpublis hed study prepared by American Cyanamid Co. and Wildlife International Ltd. 134 p. {OPPTS 850.1075}

45161311 MacGregor, J.; Nixon, W.; Palmer, S. et al. (2000) Acute Toxicity of AC 263499 Technical (Imazethapyr) to Saltwater Mysid (Mysidopsis bahia) Unde r Static

- Renewal Test Conditions: Lab Project Number: ECO 98

- 149: ECO 98

- 411: CY 306. Unpublished study prepared by American Cyanamid Co. and Wildlife International Ltd. 133 p. {OPPTS 850.1035}

45161312 MacGregor, J.; Nixon, W.; Palmer, S. et al. (2000) Acute Toxicity of AC 263499 Technical (Imazethapyr) to the Eastern Oyster (Crassostrea virginica) Under Static

- Renewal Test Conditions: Lab Project Number: ECO 98

- 150: ECO 98

- 411: CY 300. Unpublished study prepared by American Cyanamid Co. and Wildlife Int ernational Ltd. 134 p. {OPPTS 850.1025}

45161313 MacGregor, J.; Nixon, W.; Krueger, H. et al. (1999) Toxicity of AC 263499 Technical (Imazethapyr) During the Early Life

- Stages of the Fathead Minnow (Pimephales promelas): Lab Project Number: ECO 98

- 151: E CO 98

- 411: CY 307. Unpublished study prepared by American Cyanamid Co. and Wildlife International Ltd. 165 p. {OPPTS 850.1400}

45161314 MacGregor, J.; Nixon, W.; Krueger, H. et al. (1999) Toxicity of AC 263499 Technical (Imazethapyr) During the Life

- Stages of the Cladoceran (Daphnia magna): Lab Project Number: ECO 98

- 152: ECO 98

- 411: CY 304. Unpublished study prepared by American Cyanamid Co. and Wildlife International Ltd. 160 p. {O PPTS 850.1300}

45161318 Krueger, H.; Nixon, W.; Palmer, S. et al. (2000) Effect of a 2ASU Formulation of AC 263499 (Imazethapyr) on Growth of the Freshwater Diatom, Navicula pelliculosa: Lab Project Number: ECO 98

- 146: ECO

- 98

- 411: CY 303. Unpublished stu dy prepared by American Cyanamid Co. and Wildlife International Ltd. 140 p. {OPPTS 850.5400}

45161319 Krueger, H.; Nixon, W.; Palmer, S. et al. (2000) Effect of a 2ASU Formulation of AC 263499 (Imazethapyr) on Growth of the Marine Diatom, Skeletonema cos tatum: Lab Project Number: ECO 98

- 147: ECO 98

- 411: CY 302. Unpublished study prepared by American Cyanamid Co. and Wildlife International Ltd. 138 p. {OPPTS 850.5400}

45161320 Krueger, H.; Nixon, W.; Palmer, S. et al. (2000) Effect of a 2ASU Formulation of AC 263499 (Imazethapyr) on Growth of the Freshwater Algae, Anabaena flos

- aquae: Lab Project Number: ECO 98

- 145: ECO 98

- 411: CY 316. Unpublished study prepared by American Cyanamid Co. and Wildlife International Ltd. 139 p. {OPPTS 850.5400}

45161321 Kr ueger, H.; Nixon, W.; Palmer, S. et al. (2000) Effect of a 2ASU Formulation of AC 263499 (Imazethapyr) on Growth of the Green Alga, Selenastrum capricornutum: Lab Project Number: ECO 98

- 144: ECO 98

- 411: CY 313. Unpublished study prepared by American Cyanam id Co. and Wildlife International Ltd. 144 p. {OPPTS 850.5400}

45161322 Boeri, R.; Nixon, W.; Ward, T. et al. (2000) Effect of CL 266858 on the Growth of Lemna gibba G3 (Duckweed): Lab Project Number: ETX

- 99

- 125: ECO 98

- 411: CY 310. Unpublished study prepared by American Cyanamid Co., Wildlife International Ltd. and T.R. Wilbury Labs., Inc. 139 p. {OPPTS 850.4400}

45161323 Boeri, R.; Olivieri, C.; Ward, T. (2000) Effect of CL 266858 on the Growth of Selenastrum capricornutum: Lab Project Number: ETX 99

- 127: ECO 98

- 411: CY 301. Unpublished study prepared by American Cyanamid Co. and T.R. Wilbury Labs., Inc. 143 p. {OPPTS 850.5400}

45161324 Boeri, R.; Olivieri, C.; Ward, T. et al. (2000) Effect of CL 290084 on the Growth of Lemna gibba G3 (Duckweed): Lab Project Number: CY 312: ETX 99

- 128: ECO 98

- 411. Unpublished study prepared

### 33 by American Cyanamid Co., Wildlife International Ltd. and T.R. Wilbury Labs., Inc. 139 p. {OPPTS 850.4400}

45161325 Boeri, R.; Olivieri, C.; Ward, T. et al. (2000) Effect of CL 290084 on the Growth of Selenastrum capricornutum: Lab Project Number: ETX 99

- 130: ECO 98

- 411: CY 311. Unpublished study prepared by American Cyanamid Co., Wildlife International Ltd. and T.R. Wilbury Labs., Inc. 144 p. {OPPTS 850.5400}

45161326 Boeri, R.; Olivieri, C.; Ward, T. et al. (2000) Effect of CL 271197 on the Growth of Lemna gibba G3 (Duckweed): Lab Project Number: ETX 99

- 131: ECO 98

- 411: CY 314. Unpublished study prepared by American Cyanamid Co., Wildlife International Ltd. and T.R. Wilbury Labs., Inc. 145 p. {OPPTS 850.4400}

45161327 Boeri, R.; Olivieri, C.; Ward, T . et al. (2000) Effect of CL 271197 on the Growth of Selenastrum capricornutum: Lab Project Number: ETX 99

- 133: ECO 98

- 411: CY 315. Unpublished study prepared by American Cyanamid Co., Wildlife International Ltd. and T.R. Wilbury Labs., Inc. 153 p. {OPPTS 850.5400}

44996101 Ahmed, S.; Chetram, R.; Schuster, L. (1999) Tier 2 Nontarget Terrestrial Plant Vegetative Vigor Phytotoxicity Study Using AC263499 (Imazethapyr) in a 2.0 Pound Per Gallon of Aqueous Solution with Urea (2 ASU) Formulation: Lab Project N umber: 98700: ECO 98

- 115: 980023. Unpublished study prepared by ABC Labs., California. 333 p. {OPPTS 850.4250}

44996102 Ahmed, S.; Chetram, R.; Schuster, L. (1999) Tier 2 Nontarget Terrestrial Plant Seedling Emergence Phytotoxicity Study Using AC263499 (Imazethapyr) in a 2.0 Pound Per Gallon of Aqueous Solution with Urea (2 ASU) Formulation: Lab Project Number: 98699: ECO 9 8

- 114: 980022. Unpublished study prepared by ABC Labs., California. 318 p. {OPPTS 850.4225}

40996201 Forbis, A. (1988) Acute Toxicity of AC263,499 TO Selenastrum capri

- cornutum Printz: Study No. 36802. Unpublished study prepared by Analytical Bio

- Chemis try Laboratories, Inc. 183 p.

41888101 Hughes, J. (1991) The Toxicity of AC 263,499 to Lemna gibba G3: Lab Project Number: B400

- 15

- 1. Unpublished study prepare d by Malcolm Pirnie, Inc. 49 p.

159729 Forbis, A.; Georgie, L.; Burgess, D. (1985) Acute Toxic ity of AC 263,499 to Daphnia magna: Static Acute Toxicity Report #33059. Includes Bee adult toxicity dusting test. Unpublished study prepared by Analytical Bio

- Chemistry Laboratories, Inc. 37 p.

### 34 

## Appendix 1. Fate Data Description

Imazethapyr is stable to hydrolysis at all pHs tested (MRIDs 00159752 and 00159753 ), but degrades via aquatic photolysis with half

- lives of 45.8 hours in unbuffered distilled water, and 43.5 hours at pH 5, 49.8 hours at pH 7, and 56.8 hours at pH 9 (MRID 40429407 ). In a soil photolysis study (MRID 42918662), imazethapyr degraded with a half

- life greater than 4 weeks

. Imazethapyr does not appear to volatilize appreciably under environmental conditions ( Vapor Pressure of 5.25 × 10 - 8 

### mm Hg @ 25oC; MRID 46841305 ).

Metabolism In aerobic soil metabolism studies, imazethapyr degraded with a half

- life of ~33 months (MRID 00159754

– also numbered 00262932), degraded with a half

- life of >1 year in sandy loam soil, loamy sand, and clay loam soils (MRID 40074201), and degraded with a half

- life of 158 days in sandy loam soil (MRID 45161328). In an anaerobic soil metabolism study (MRID 40429409), imazethapyr degraded with a half

- life of > 2 months in sandy loam soil. In an aerobic aquatic metabolism study (MRID 45161330 ), imazethapyr de graded with a half

- life of 456 days and 333 days in a silt loam (Pond) and loam (river) sediment systems , respectively. In an anaerobic aquatic metabolism study (MRID 45161329), imazethapyr had half

- lives ranging from 976 to >1034 days in silt loam (pond) and loam (River) sediment/water systems.

Dissipation In terrestrial field dissipation studies, i mazethapyr dissipated from the upper 3 inches of soil with half

- lives of 4 to 14 days in three field plots of silt loam located in Bowling Green, KY; 3 to 7 days and 14 to 60 days in two field plots of loamy sand soil located in Tifton, GA; 30 to 61 days in three field plots of silt loam soil located in York, NE; 61 to 117 days and 95 to 340 days in three field plots of loam soil located in Webster City, IA; a nd 7 to 14 days and 59 to 120 days in three field plots of silt loam soil located in Savory, IL (MRID 40429410) and dissipated from 18 inches of soil with a half

- life of 36 days in field plots of loamy sand soil in Tifton, GA (MRID 41467701). Aqu atic fiel d dissipation studies indicate maximum imazethapyr concentrations in rice paddy water are substantially lower (2.40 ug/L) than model predictions ( i.e. , Tier 1 rice model estimates) , produced a 50% dissipation time (DT 50 

### ) of 8.4 days from d ay 0.1 to 28 and 145 days from d ay 28 to 359 in a sandy loam soil at Cheneyville, LA ( MRID 45161333 ), produced DT 50 

### ’ s of 14 days from day 0 to 28 and > 1 year from d ay 14 to 360 in Sharkey silty clay loam soil (MRID 45161332 ), and produced a DT 50 

### of 58 days in soil under s imulated rice culture conditions (MRID 451613 41 ). Degradation products of are shown in Table 4

- 1

.
Mobility Imazethapyr is expected to be mobile in soil. The average K f of imazethapyr in five agricultural soils is 0.62 L/kg (range = 0.45 to 0.82). The average K f of CL 266,858 in four non

- sand agricultural soils is 5.43 L/kg (range = 1.55 to 14.9 ). The average K f of CL 271,197 in five agricultural soils is 32.1 L/kg (range = 2.12 to 82.0 ). The average K f of CL 290,084 in five agricultural soils is 0.36 L/kg (range = 0.16 to 0. 6 2) ( MRID s 00262932, 45161329 )

.

### 35 Accumulation Total [ 14 

### C] imazethapyr residues accumulated in bluegill sunfish ( Lepomis macrochirus ) with a maximum bioaccumulation factor of 1.6 × in viscera and did not accumulate in fillet and whole fish during 28 days of exposure to [ 14 

### C]imazethapyr residues at 4.6

- 4.9 ppm in a flow

- through system. With the exception of viscera sampled after 7 days of exposure, in which imazethapyr residues were 7.5 ppm, imazethapyr residues were not detected (LOD = 3.3 μ g/g) in fillet, viscera, and whole fish during 28 days of exposure and 14 days of depuration ( MRID 40429413 ).

Prospective ground water monitoring studies in Indiana and Georgia indicate maximum imazethapyr concentrations in shallow ground water ranged from 0.06 to 0.07 ug/L (Multiple MRIDs).