UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON. DC 20460 

OFFICE OF CHEMICAl SAFFTY AND POLLUTION PRr VENTION 

PC Codes: 128922 + 128923 

DP Barcode: D415245 

Date: March 19,2014 

MEMORANDUM 

Subject: 

To: 

From: 

Registration Review Problem Formulation for Imazethapyr and Imazethapyr 

Ammonium Salt 

Katherine St. Clair, Chemical Review Manager 

Kevin Costello, Branch Chief 

Risk Management and Implementation Branch II 

Pesticide Re-evaluation Division (7508P) 

Edward Odenkirchen, Ph.D., Senior Scient. ist ei ( \ \ ~ Stephen Wente, Ph.D., Biologist l , ~\t- J'--0..~ 3 \.Ci. 1 \ 

Environmental 

Sujatha Sankula, 

Risk 

Ph.D., 

Bran

Branch 

ch 1 

Chief _; 1 ~ 

Environmental Fate and Effects Division (7507P) ?/I 1 fto/ 

Office of Pesticide Programs .:> . / ' 

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

(attached) for the environmental fate, ecological risk, endangered 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 assessment 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 degradates. It describes the preliminary ecological risk hypothesis and 

analysis plan for evaluating 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 studies that should be included in a data call-in (DCI) to address 

uncertainties surrounding the environmental fate and potential ecological effects of imazethapyr. 

1 
2

REGISTRATION REVIEW

PROBLEM FORMULATION

Imazethapyr and the Ammonium Salt of Imazethapyr

N N

N

COOH

O

Imazethapyr

N N

N

COO- + NH4+

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 Biologist

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 Assessments............................................................................................................. 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 References............................................................................................................................. 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 ecological risk assessments in support of 

registration review and provides an overview of the environmental fate, ecological effects, and 

potential risks associated with the use of imazethapyr and its ammonium salt as well as

uncertainties unique to risk assessment 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 number 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 – maximum number of

applications per year, Maximum per year application rate, and minimum retreatment 

interval. 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 would 

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 technical 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 environmental 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. Imazethapyr is applied primarily to soybean, alfalfa, 

dry beans/peas as well as genetically modified corn and rice1. Corn and rice are naturally 

sensitive to this herbicide; therefore, imazethapyr can only be used in imidazolinone tolerant 

corn and rice varieties. 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 in 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 code 128923).

Imazethapyr is a systemic herbicide. It is absorbed by both roots and foliage and translocated via 

both xylem and phloem. It accumulates 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, nonagricultural 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, soybeans (unspecified), 

soybeans, edible, and trefoil.
6

The mechanism of action of imazethapyr involves reducing levels of three branched 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 

causes a disruption in protein synthesis 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 affected 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 on 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 (LD50 >1000 ug/bee) to honeybees; therefore 

low risk was assumed for 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, 

indicated high toxicity to non-target terrestrial plants.

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 invertebrates 

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 below

concern levels.

o Risk to estuarine/marine invertebrates and fish and freshwater 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 clover. Additionally, there was no concern for acute risk for bluegreen 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 linkage 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 drinking water assessment (DWA) was performed for the use of imazethapyr on rice 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 imazethapyr concentration in 

aquatic environments and drinking water was not expected to exceed 93 μg/L. This 

concentration is expected to be conservative because it represents imazethapyr concentrations in 

rice paddy water without consideration of degradation or dilution. Aquatic field dissipation 

studies (MRIDs 45161332 and 45161333) indicated maximum imazethapyr concentrations in 

rice paddy water are substantially lower (2.40 μg/L) than model predictions. SCI-GROW 

modeling predicted peak and chronic imazethapyr concentrations in ground water are not 

expected to exceed 8.97 μg/L. Progress reports for prospective ground water monitoring studies 

in Indiana and Georgia conducted at the time of this DWA indicated maximum imazethapyr 

concentrations in shallow ground water ranged from 0.06 to 0.07 μg/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 Act2

. In addition, no Total Maximum Daily Loads 

(TMDL) have been developed for imazethapyr3

. The Impaired Waters and Total Maximum 

Daily Loads website can be consulted for more information4. Aquatic benchmarks have been 

established for imazethapyr5. Any data submitted or otherwise located as part of the registration 

review process may be used to update aquatic life 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 the OPP Standard Operating 

Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s 

Registration Review Risk Assessment and Management Process6, in order to ensure they can be 

used quantitatively or qualitatively in pesticide risk assessments.

4 Overview of Imazethapyr Use

Registered agricultural use sites for imazethapyr and imazethapyr ammonium salt include: 

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, soybeans (unspecified), 

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_

group_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-of-way (railroad), 

utility poles/rights-of-way. Registered non-agricultural use sites for imazethapyr ammonium salt

include: airports, grasses, clover, fencerows, industrial areas, institutions, lespedeza, lupine, 

military installations, non-crop areas, 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 imazethapyr ammonium salt

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 than 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 identified 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 Crop 

Cycle

Max App 

Rate per

Crop Cycle

(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.

Imazethapyr is persistent and mobile in terrestrial and aquatic environments. The major 

dissipation pathways are photodegradation in water, surface 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-lives 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-lives of 456 days (pond

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 (river water).

In terrestrial field dissipation studies, imazethapyr dissipated from the upper 3 inches of soil with 

half-lives of 3 to 340 days. Aquatic field dissipation studies yielded a maximum imazethapyr 

concentration in rice paddy water of 2.40 μg/L. Parent dissipation was biphasic in these aquatic 

field dissipation studies.

Chemical 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 evaluating 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 accumulate 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 Fate Studies

Imazethapyr (Parent)

Imazethapyr

Synonym: AC 263499

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-1Himidazol-2-yl]-5-ethyl-3-pyridinecarboxylic acid

CAS #: 81335-77-5

Formula: C15H19N3O3

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 KF: 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: C16H21N3O3

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

COOCH3

O

CL 266858

CAS #: 102771-62

Formula: C13H15N3O4

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 KF: 5.43 L/kg (MRID 45161331)

Predicted Koc: 142.3 L/kg (EPI Suite MCI method)

Maximum % Formation:

Aerobic soil metabolism – 11.74% (increasing at study end: 124 

days) – major degradate

Aquatic field dissipation – <5%

N N

N

COOH

O

HO

CL 271197

Synonym: 5-Ethyl 2,3-pyridinedicarboxylic acid

CAS #: 102268-15-5

Formula: C9H9NO4

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 KF: 32.1 L/kg (MRIDs 00159755, 

45161331)

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: C15H19N3O4

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 soil metabolism – 1.92% (0 days; may be impurity)

Aquatic field dissipation – <5%

N N

N

COOH

O

HO

CL 288903

CAS #: 113052-10

Formula: C15H17N3O4

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 metabolism – 2.42% (84 days)

N N

N

COOH

O

O
12

CL 290084

Synonym: 5-Ethyl 3-pyridinecarboxylic acid

Formula: C8H9NO2

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 KF: 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: C15H21N3O4

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 soil metabolism – 1.69% (61 days)

Anaerobic aquatic metabolism – 1.0% (14 days)

Aerobic aquatic metabolism – 0.94% (14 days)

N

C

COOH

O

N

H

C

O

NH2

CL 354825

Formula: C14H15N3O5

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 soil metabolism – 3.24% (42 days)

Anaerobic aquatic metabolism – 3.1% (30 days)

Aerobic aquatic metabolism – 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 shallow ground water of 0.07 μg/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 those 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: 80 - 100 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 KOW(@22 - 27oC) 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 00159753

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 halflives

~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 halflife >2 months in sandy loam soil MRID 40429409

Aerobic Aquatic Metabolism halflives456 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 halflives

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 plots 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 acetolactate 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 species 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 anticipated 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 includes 

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 chronic 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 ingredient 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 (If Applicable)

Source & 

Classification

Rat acute oral (purity 

not reported)

Norway rat 

(Rattus sp.)

LD50 > 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.)

LC50 >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)

LD50 > 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)

LD50 > 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)

LC50 > 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)

LC50 > 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

EC25 = >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

EC25 = 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 (If Applicable)

Source & 

Classification

Most sensitive 

dicot: tomato

EC25 = 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 LC50 = 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 LC50 > 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 LC50 = 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 LC50 = 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 LC50 > 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 LC50 > 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 EC50 >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 EC50 > 24.42 mg a.i./L 

NOEC = 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 LC50 > 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 EC50 > 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 EC50 > 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 EC50 = 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 (If Applicable)

Source & 

Classification

Aquatic non-vascular 

plant

2ASU formulation

(22.2, corrected)

Freshwater diatom

(Navicula pelliculosa)

5-day EC50 > 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 EC50 > 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 EC50 = 8.1 μg a.i.//L

NOEC = 2.8 μg 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 mortality 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 EC50 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 aquatic 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 to 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 

hours 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/TEP (%) Species Toxicity Endpoints, Effects & Acute Toxicity Classification (If Applicable)

Source & 

Classification

Freshwater invertebrate acute

CL266858 (99)

Water flea

(Daphnia magna)

48-hr EC50 > 100 mg a.i./L 

48-hr NOEC = 100 mg a.i./L

Practically non-toxic

MRID 45161309

Supplemental 

and suitable for 

quantitative use

Freshwater invertebrate acute

CL271197 (99.1)

Water flea

(Daphnia magna)

48-hr EC50 > 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/TEP (%) Species Toxicity Endpoints, Effects & Acute Toxicity Classification (If Applicable)

Source & 

Classification

Freshwater invertebrate acute

CL290084 (100)

Water flea

(Daphnia magna)

48-hr EC50 > 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 EC50 = 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 EC50 = 12.4 mg a.i./L 

5-day NOEC < 6.87 mg a.i./L 

MRID 45161327

Supplemental

and suitable for 

quantitative use

Aquatic non-vascular plant

CL290084 (100)

Green alga

(Selenastrum 

capricornutum)

5-day EC50 = 28.77 mg a.i./L 

5-day NOEC = 6.11 mg a.i./L 

MRID 45161325

Supplemental

and suitable for 

quantitative use

Aquatic vascular plant 

CL271197 (99.1)

Duckweed 

(Lemna gibba)

14-day EC50 > 101 ug/L

14-day NOEC = 49.8 μg/L

MRID 45161326

Supplemental

and suitable for 

quantitative use

Aquatic vascular plant

CL290084 (100)

Duckweed 

(Lemna gibba)

14-day EC50 = 37.15 ug/L

14-day NOEC = 23.54 μg/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 endpoints. In general, the QSAR is poorly predictive of actual 

observed toxicity in parent imazethapyr. Only a few general 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. This 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 

of 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 inappropriate 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 predicted 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. Given the 

relatively long persistence of the parent compound expected in the environment, 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 for 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 substantial 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 LC50 240 1240 ND 220 ND 20269 ND 7.6 ND 2155 ND 23549 ND 1888 ND 10758 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/LC50 >1000 860 >100

(mort. >50)

624 >100 

(mort. >25)

11027 ND 5.8 ND 1346 ND 9457 >100 775 ND 5006 ND 6689

Chronic Value 103 11.4 ND 47.6 ND 1224 ND 0.077 ND 11.6 ND 125 ND 10.2 ND 66.0 ND 88.2

Green algae 96-hr EC50 >22.4 48.3 12.4 173 28.77 4644 ND 0.37 ND 12.2 ND 127 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 System8 (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) associated 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 incidents 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 reports 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 Pathways 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, and 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 to 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 bodyweight 

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 contact 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 spray 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 spray 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 assessment 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 

imazethapyr by dividing estimated exposure concentrations (EECs) 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 concern (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 

opening of the Registration Review docket.

8.1 Stressors of Concern

8.1.1 Ecological Risk Assessment

The risk assessment will consider parent 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 for 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 

significant 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 

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

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

from changes in structure and functional characteristics of the affected communities.

9 Endangered Species Assessments

Consistent with 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. This assessment will be conducted in 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, nor 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 effects data that are needed to 

complete an environmental fate and ecological risk assessment in support of the Registration 

Review 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 0015975200159753

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 46123702 In review No
24

11.2 Ecological Effects Data

Table 11-2 provides ecological effects studies by MRID that offer data for each guideline 

requirement as well as study classifications and whether or not further data are needed to support 

the Registration Review ecological risk assessment (i.e., whether there is a data gap).

Table 11-2. Registrant-Submitted Ecological Effects Data for Imazethapyr/Degradates and 

Remaining Data Gaps

Guideline Description MRID/Source* Classification Data Needed for 

Risk Assessment

Justification

850.1010

Acute toxicity 

freshwater 

invertebrates 

00159729

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

The study provides 

sufficient 

information for 

quantitative use.

850.1075

Acute toxicity

freshwater fish

(cold water 

species)

00159728

45161312 Acceptable

No

Acute toxicity

freshwater fish 

(warm water 

species)

00159727

45161305 

45161306

00159726

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

The 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 lifestage

(freshwater)

45161313 Acceptable No
25

Guideline Description MRID/Source* Classification Data Needed for 

Risk Assessment

Justification

Fish early lifestage

(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)

00159723

00159722

Acceptable

Acceptable No

Avian oral toxicity

(passerine species) -- -- No

Avian 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 

than 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 nontoxic acidic 

compounds tested 

with passerines.

850.2200

Avian dietary 

toxicity 

(upland game 

species)

00159725 Acceptable No

Avian dietary 

toxicity 

(waterfowl 

species)

00159724 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 00159729 PendingReview Yes

850.3030

Honey bee toxicity 

of residues on 

foliage

-- -- Yes; 

The need for the 

study depends on the 

final review of

850.3020

NonguidelineHoney bee acute 

oral toxicity -- -- Yes

The need for the 

study depends on the 

final review of

850.3020

NonguidelineHoney bee larval 

toxicity -- -- Yes

The need for the 

study depends on the 

final review of

850.3020

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 nonvascular 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 nonvascular 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 yields 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 passerine 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 attractive 

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

OSCPP 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 orders 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 conservative 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 organic carbon and low acute and chronic toxicity of the pesticide 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 Tier 2 aquatic plant toxicity data set, there appears to be no

benefit afforded to the certainty of a risk assessment that would assume equipotence with 

parent in the absence of any empirical 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 Science. 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) Pursuit 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 AC 263,499 (2-[4,5-Dihydro-4-methyl-4-(1-methyl-ethyl)-5-oxo-1Himidazol-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.

40074201 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 Sandy 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 Studies: 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. 122 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 Aquatic 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 

Project 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-methylethyl)-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 Products 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): Residues 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 Sediment 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.

45161333 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 Metabolism 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 Bioconcentration of [Car- bon 14]-AC 263,499 by Bluegill 

Sunfish (Lepomis macrochirus): Laboratory Report No. 34643. Unpublished study prepared by Analytical 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 Bobwhite 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.; Fuhrman, 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. 

205 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 Toxicity 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 International 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.; Mulligan, 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 MacGregor, 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 International 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 Laboratories, 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. Unpublished 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) Under 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 International 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: ECO 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. {OPPTS 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 study 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 costatum: 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 Krueger, 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 Cyanamid 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 Number: 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 98-114: 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-Chemistry 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 prepared by Malcolm Pirnie, Inc. 49 p.

159729 Forbis, A.; Georgie, L.; Burgess, D. (1985) Acute Toxicity 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 degraded 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, imazethapyr 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; and 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). Aquatic field 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 (DT50) of 8.4 days from day 0.1 to 28 and 

145 days from day 28 to 359 in a sandy loam soil at Cheneyville, LA (MRID 45161333), 

produced DT50’s of 14 days from day 0 to 28 and > 1 year from day 14 to 360 in Sharkey silty 

clay loam soil (MRID 45161332), and produced a DT50 of 58 days in soil under simulated rice 

culture conditions (MRID 45161341). Degradation products of are shown in Table 4-1.

Mobility

Imazethapyr is expected to be mobile in soil. The average Kf of imazethapyr in five agricultural 

soils is 0.62 L/kg (range = 0.45 to 0.82). The average Kf of CL 266,858 in four non-sand 

agricultural soils is 5.43 L/kg (range = 1.55 to 14.9). The average Kf of CL 271,197 in five 

agricultural soils is 32.1 L/kg (range = 2.12 to 82.0). The average Kf of CL 290,084 in five 

agricultural soils is 0.36 L/kg (range = 0.16 to 0.62) (MRIDs 00262932, 45161329). 
35

Accumulation

Total [14C] 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 [14C]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 μg/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).